PARADIGM pathway analysis of mRNASeq expression data - Lung Adenocarcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
Glypican 2 network	177
Angiopoietin receptor Tie2-mediated signaling	134
FOXM1 transcription factor network	125
Aurora B signaling	117
Signaling events mediated by the Hedgehog family	93
Aurora C signaling	71
Endothelins	71
PLK1 signaling events	66
HIF-1-alpha transcription factor network	63
Visual signal transduction: Cones	57

Pathway.Name	Significance.Ratio	Avg.Num.Perturbations	Total.Perturbations	Num.Entities	Min.Mean.Truth	Max.Mean.Truth	Min.Mean.Within	Max.Mean.Within	Min.Mean.Any	Max.Mean.Within.1
Glypican 2 network	0.3782	177	710	4	-0.2	-0.13	1000	-1000	-0.029	-1000
Angiopoietin receptor Tie2-mediated signaling	0.2863	134	11798	88	-0.6	0.056	1000	-1000	-0.1	-1000
FOXM1 transcription factor network	0.2671	125	6406	51	-0.57	0.01	1000	-1000	-0.18	-1000
Aurora B signaling	0.2500	117	7889	67	-0.42	0.01	1000	-1000	-0.059	-1000
Signaling events mediated by the Hedgehog family	0.1987	93	4875	52	-0.37	0.18	1000	-1000	-0.065	-1000
Aurora C signaling	0.1517	71	501	7	-0.27	0.005	1000	-1000	-0.036	-1000
Endothelins	0.1517	71	6876	96	-0.31	0.02	1000	-1000	-0.067	-1000
PLK1 signaling events	0.1410	66	5628	85	-0.3	0.06	1000	-1000	-0.04	-1000
HIF-1-alpha transcription factor network	0.1346	63	4835	76	-0.49	0.016	1000	-1000	-0.17	-1000
Visual signal transduction: Cones	0.1218	57	2170	38	-0.16	0.01	1000	-1000	-0.058	-1000
Signaling mediated by p38-alpha and p38-beta	0.1154	54	2393	44	-0.12	0.01	1000	-1000	-0.048	-1000
IL4-mediated signaling events	0.1132	53	4860	91	-0.78	0.51	1000	-1000	-0.17	-1000
Signaling events regulated by Ret tyrosine kinase	0.1111	52	4303	82	-0.16	0.01	1000	-1000	-0.071	-1000
BMP receptor signaling	0.1004	47	3811	81	-0.35	0.027	1000	-1000	-0.079	-1000
amb2 Integrin signaling	0.1004	47	3877	82	-0.47	0.01	1000	-1000	-0.07	-1000
Fc-epsilon receptor I signaling in mast cells	0.0962	45	4431	97	-0.15	0.028	1000	-1000	-0.077	-1000
Osteopontin-mediated events	0.0940	44	1675	38	-0.37	0.011	1000	-1000	-0.09	-1000
TCGA08_retinoblastoma	0.0940	44	354	8	-0.16	0.05	1000	-1000	-0.021	-1000
TCGA08_p53	0.0876	41	288	7	-0.11	0.054	1000	-1000	-0.013	-1000
FOXA2 and FOXA3 transcription factor networks	0.0855	40	1847	46	-0.49	0.016	1000	-1000	-0.1	-1000
Visual signal transduction: Rods	0.0855	40	2098	52	-0.15	0.01	1000	-1000	-0.067	-1000
Arf6 signaling events	0.0769	36	2239	62	-0.19	0.011	1000	-1000	-0.053	-1000
Glucocorticoid receptor regulatory network	0.0769	36	4210	114	-0.4	0.25	1000	-1000	-0.074	-1000
LPA4-mediated signaling events	0.0726	34	416	12	-0.12	0.012	1000	-1000	-0.022	-1000
Canonical Wnt signaling pathway	0.0726	34	1739	51	-0.34	0.15	1000	-1000	-0.054	-1000
Thromboxane A2 receptor signaling	0.0684	32	3437	105	-0.091	0.028	1000	-1000	-0.065	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0684	32	1665	52	-0.25	0.043	1000	-1000	-0.056	-1000
p75(NTR)-mediated signaling	0.0662	31	3954	125	-0.3	0.02	1000	-1000	-0.086	-1000
Glypican 1 network	0.0662	31	1492	48	-0.12	0.019	1000	-1000	-0.051	-1000
Integrins in angiogenesis	0.0641	30	2595	84	-0.37	0.024	1000	-1000	-0.072	-1000
Effects of Botulinum toxin	0.0641	30	801	26	-0.09	0.01	1000	-1000	-0.057	-1000
Syndecan-1-mediated signaling events	0.0620	29	1000	34	-0.34	0.01	1000	-1000	-0.052	-1000
Ephrin B reverse signaling	0.0620	29	1410	48	-0.093	0.055	1000	-1000	-0.056	-1000
EGFR-dependent Endothelin signaling events	0.0620	29	616	21	-0.091	0.01	1000	-1000	-0.055	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0620	29	3507	120	-0.25	0.2	1000	-1000	-0.066	-1000
Aurora A signaling	0.0556	26	1582	60	-0.3	0.015	1000	-1000	-0.052	-1000
IL23-mediated signaling events	0.0556	26	1584	60	-0.28	0.016	1000	-1000	-0.17	-1000
Presenilin action in Notch and Wnt signaling	0.0534	25	1548	61	-0.34	0.02	1000	-1000	-0.062	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0534	25	1752	68	-0.14	0.03	1000	-1000	-0.13	-1000
IL6-mediated signaling events	0.0513	24	1836	75	-0.33	0.042	1000	-1000	-0.095	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0491	23	786	33	-0.15	0.025	1000	-1000	-0.058	-1000
PDGFR-alpha signaling pathway	0.0449	21	958	44	-0.31	0.027	1000	-1000	-0.059	-1000
Wnt signaling	0.0449	21	148	7	-0.061	0.009	1000	-1000	-0.023	-1000
Class IB PI3K non-lipid kinase events	0.0449	21	63	3	-0.013	-1000	1000	-1000	-0.011	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0406	19	672	34	-0.038	0.01	1000	-1000	-0.052	-1000
ErbB4 signaling events	0.0406	19	1377	69	-0.19	0.2	1000	-1000	-0.085	-1000
Syndecan-3-mediated signaling events	0.0406	19	680	35	-0.2	0.01	1000	-1000	-0.052	-1000
Nongenotropic Androgen signaling	0.0406	19	998	52	-0.059	0.01	1000	-1000	-0.054	-1000
Regulation of Androgen receptor activity	0.0406	19	1358	70	-0.26	0.026	1000	-1000	-0.063	-1000
PLK2 and PLK4 events	0.0385	18	54	3	-0.019	-0.004	1000	-1000	-0.014	-1000
HIF-2-alpha transcription factor network	0.0385	18	791	43	-0.12	0.049	1000	-1000	-0.093	-1000
Coregulation of Androgen receptor activity	0.0342	16	1241	76	-0.15	0.018	1000	-1000	-0.046	-1000
Syndecan-2-mediated signaling events	0.0342	16	1137	69	-0.093	0.032	1000	-1000	-0.053	-1000
Reelin signaling pathway	0.0342	16	922	56	-0.096	0.01	1000	-1000	-0.07	-1000
Syndecan-4-mediated signaling events	0.0342	16	1078	67	-0.17	0.015	1000	-1000	-0.085	-1000
Noncanonical Wnt signaling pathway	0.0321	15	392	26	-0.061	0.01	1000	-1000	-0.067	-1000
Nectin adhesion pathway	0.0321	15	978	63	-0.042	0.013	1000	-1000	-0.059	-1000
IL12-mediated signaling events	0.0278	13	1194	87	-0.097	0.038	1000	-1000	-0.12	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0278	13	1018	78	-0.038	0.038	1000	-1000	-0.078	-1000
Caspase cascade in apoptosis	0.0256	12	939	74	-0.041	0.031	1000	-1000	-0.048	-1000
Signaling events mediated by PTP1B	0.0256	12	984	76	-0.091	0.017	1000	-1000	-0.069	-1000
Signaling events mediated by HDAC Class III	0.0256	12	512	40	-0.12	0.018	1000	-1000	-0.04	-1000
S1P1 pathway	0.0256	12	456	36	-0.066	0.011	1000	-1000	-0.051	-1000
FAS signaling pathway (CD95)	0.0256	12	598	47	-0.24	0.012	1000	-1000	-0.043	-1000
EPHB forward signaling	0.0256	12	1093	85	-0.066	0.05	1000	-1000	-0.077	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0256	12	1579	125	-0.31	0.034	1000	-1000	-0.08	-1000
LPA receptor mediated events	0.0256	12	1297	102	-0.12	0.03	1000	-1000	-0.074	-1000
BCR signaling pathway	0.0256	12	1204	99	-0.13	0.027	1000	-1000	-0.075	-1000
Signaling events mediated by PRL	0.0256	12	410	34	-0.18	0.021	1000	-1000	-0.039	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0235	11	612	54	-0.14	0.021	1000	-1000	-0.083	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0235	11	973	85	-0.041	0.032	1000	-1000	-0.069	-1000
TCR signaling in naïve CD8+ T cells	0.0235	11	1030	93	-0.073	0.042	1000	-1000	-0.077	-1000
BARD1 signaling events	0.0214	10	622	57	-0.18	0.03	1000	-1000	-0.062	-1000
Ephrin A reverse signaling	0.0214	10	72	7	-0.01	0.008	1000	-1000	-0.026	-1000
IL1-mediated signaling events	0.0214	10	645	62	-0.14	0.049	1000	-1000	-0.084	-1000
S1P5 pathway	0.0214	10	186	17	-0.035	0.03	1000	-1000	-0.043	-1000
Calcium signaling in the CD4+ TCR pathway	0.0214	10	324	31	-0.1	0.012	1000	-1000	-0.09	-1000
Regulation of p38-alpha and p38-beta	0.0192	9	496	54	-0.071	0.019	1000	-1000	-0.051	-1000
IL2 signaling events mediated by STAT5	0.0192	9	201	22	-0.12	0.055	1000	-1000	-0.047	-1000
Plasma membrane estrogen receptor signaling	0.0192	9	797	86	-0.035	0.03	1000	-1000	-0.068	-1000
S1P4 pathway	0.0192	9	244	25	-0.035	0.01	1000	-1000	-0.045	-1000
ErbB2/ErbB3 signaling events	0.0171	8	584	65	-0.094	0.019	1000	-1000	-0.06	-1000
Ras signaling in the CD4+ TCR pathway	0.0171	8	137	17	-0.014	0.021	1000	-1000	-0.04	-1000
Regulation of nuclear SMAD2/3 signaling	0.0150	7	1082	136	-0.11	0.05	1000	-1000	-0.067	-1000
IL27-mediated signaling events	0.0150	7	358	51	-0.11	0.011	1000	-1000	-0.068	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0128	6	187	28	-0.035	0.02	1000	-1000	-0.049	-1000
Signaling mediated by p38-gamma and p38-delta	0.0128	6	94	15	0	0.022	1000	-1000	-0.028	-1000
Arf6 trafficking events	0.0128	6	458	71	-0.082	0.034	1000	-1000	-0.068	-1000
Regulation of Telomerase	0.0128	6	679	102	-0.093	0.03	1000	-1000	-0.1	-1000
Insulin Pathway	0.0128	6	473	74	-0.15	0.03	1000	-1000	-0.075	-1000
VEGFR1 specific signals	0.0128	6	379	56	-0.31	0.041	1000	-1000	-0.064	-1000
p38 MAPK signaling pathway	0.0128	6	272	44	-0.081	0.026	1000	-1000	-0.06	-1000
Signaling events mediated by HDAC Class II	0.0107	5	395	75	-0.047	0.027	1000	-1000	-0.058	-1000
JNK signaling in the CD4+ TCR pathway	0.0107	5	88	17	-0.013	0.031	1000	-1000	-0.057	-1000
Cellular roles of Anthrax toxin	0.0107	5	222	39	-0.046	0.015	1000	-1000	-0.028	-1000
Hedgehog signaling events mediated by Gli proteins	0.0107	5	371	65	-0.17	0.054	1000	-1000	-0.057	-1000
Ceramide signaling pathway	0.0107	5	401	76	-0.091	0.036	1000	-1000	-0.049	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0107	5	417	83	-0.068	0.04	1000	-1000	-0.072	-1000
Retinoic acid receptors-mediated signaling	0.0107	5	336	58	-0.17	0.032	1000	-1000	-0.066	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0107	5	371	74	-0.11	0.06	1000	-1000	-0.074	-1000
IFN-gamma pathway	0.0085	4	295	68	-0.081	0.047	1000	-1000	-0.086	-1000
Signaling events mediated by HDAC Class I	0.0085	4	423	104	-0.047	0.043	1000	-1000	-0.064	-1000
FoxO family signaling	0.0085	4	317	64	-0.13	0.055	1000	-1000	-0.075	-1000
IL2 signaling events mediated by PI3K	0.0085	4	254	58	-0.15	0.066	1000	-1000	-0.079	-1000
Class I PI3K signaling events	0.0085	4	344	73	-0.071	0.024	1000	-1000	-0.058	-1000
Circadian rhythm pathway	0.0064	3	79	22	-0.03	0.033	1000	-1000	-0.049	-1000
Arf6 downstream pathway	0.0064	3	164	43	-0.041	0.026	1000	-1000	-0.036	-1000
TCGA08_rtk_signaling	0.0064	3	91	26	-0.022	0.037	1000	-1000	-0.019	-1000
IGF1 pathway	0.0064	3	212	57	-0.037	0.04	1000	-1000	-0.076	-1000
S1P3 pathway	0.0064	3	158	42	-0.034	0.023	1000	-1000	-0.049	-1000
TRAIL signaling pathway	0.0043	2	124	48	-0.009	0.039	1000	-1000	-0.062	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0043	2	116	45	-0.013	0.061	1000	-1000	-0.079	-1000
E-cadherin signaling in the nascent adherens junction	0.0043	2	182	76	-0.043	0.05	1000	-1000	-0.068	-1000
Rapid glucocorticoid signaling	0.0043	2	59	20	-0.007	0.01	1000	-1000	-0.031	-1000
PDGFR-beta signaling pathway	0.0043	2	219	97	-0.037	0.048	1000	-1000	-0.073	-1000
Canonical NF-kappaB pathway	0.0021	1	44	39	-0.014	0.066	1000	-1000	-0.072	-1000
a4b1 and a4b7 Integrin signaling	0.0021	1	8	5	-0.002	0.009	1000	-1000	-0.033	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0021	1	62	37	-0.005	0.037	1000	-1000	-0.046	-1000
ceramide signaling pathway	0.0021	1	54	49	-0.013	0.039	1000	-1000	-0.045	-1000
E-cadherin signaling events	0.0021	1	8	5	-0.002	0.01	1000	-1000	-0.037	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	11	23	-0.003	0.036	1000	-1000	-0.063	-1000
EPO signaling pathway	0.0000	0	50	55	-0.005	0.058	1000	-1000	-0.085	-1000
Insulin-mediated glucose transport	0.0000	0	24	32	-0.004	0.035	1000	-1000	-0.055	-1000
mTOR signaling pathway	0.0000	0	14	53	-0.001	0.026	1000	-1000	-0.054	-1000
Class I PI3K signaling events mediated by Akt	0.0000	0	25	68	-0.034	0.046	1000	-1000	-0.058	-1000
Paxillin-dependent events mediated by a4b1	0.0000	0	24	36	-0.003	0.018	1000	-1000	-0.056	-1000
Atypical NF-kappaB pathway	0.0000	0	21	31	-0.002	0.038	1000	-1000	-0.048	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	9	27	-0.001	0.023	1000	-1000	-0.05	-1000
E-cadherin signaling in keratinocytes	0.0000	0	28	43	-0.007	0.037	1000	-1000	-0.057	-1000
Arf1 pathway	0.0000	0	20	54	-0.006	0.024	1000	-1000	-0.044	-1000
Alternative NF-kappaB pathway	0.0000	0	0	13	0	0.01	1000	-1000	-0.052	-1000
Total	NA	2787	160870	7203	-19	-1000	131000	-131000	-8.3	-131000

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.15	0.24	-9999	-0.51	145	145
GPC2	-0.13	0.23	-9999	-0.51	123	123
GPC2/Midkine	-0.2	0.23	-9999	-0.43	221	221
neuron projection morphogenesis	-0.2	0.23	-9999	-0.43	221	221

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.41	0.52	-10000	0	-0.95	218	218
NCK1/PAK1/Dok-R	-0.21	0.22	-10000	0	-0.43	218	218
NCK1/Dok-R	-0.54	0.61	-10000	0	-1.2	218	218
PIK3CA	0.011	0.001	-10000	0	-10000	0	0
mol:beta2-estradiol	0.056	0.1	0.24	107	-10000	0	107
RELA	0.01	0	-10000	0	-10000	0	0
SHC1	0.005	0.005	-10000	0	-10000	0	0
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	0.006	0.2	0.25	104	-0.51	48	152
TNIP2	0.01	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.48	0.54	-10000	0	-1	218	218
FN1	0.005	0.047	-10000	0	-0.5	4	4
PLD2	-0.52	0.66	-10000	0	-1.2	218	218
PTPN11	0.01	0	-10000	0	-10000	0	0
GRB14	-0.025	0.13	-10000	0	-0.51	31	31
ELK1	-0.45	0.57	-10000	0	-1	218	218
GRB7	0.003	0.058	-10000	0	-0.51	6	6
PAK1	0.01	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.51	0.58	-10000	0	-1.1	218	218
CDKN1A	-0.28	0.35	-10000	0	-0.65	212	212
ITGA5	0.008	0.034	-10000	0	-0.51	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.54	0.61	-10000	0	-1.2	218	218
CRK	0.01	0	-10000	0	-10000	0	0
mol:NO	-0.29	0.37	-10000	0	-0.68	218	218
PLG	-0.53	0.66	-10000	0	-1.2	218	218
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.39	0.48	-10000	0	-0.9	218	218
GRB2	0.01	0	-10000	0	-10000	0	0
PIK3R1	0.005	0.024	-10000	0	-0.5	1	1
ANGPT2	-0.21	0.29	-10000	0	-0.65	115	115
BMX	-0.6	0.69	-10000	0	-1.3	218	218
ANGPT1	-0.29	0.53	-10000	0	-1.3	107	107
tube development	-0.32	0.4	-10000	0	-0.74	217	217
ANGPT4	-0.26	0.25	-10000	0	-0.5	240	240
response to hypoxia	-0.029	0.035	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.56	0.69	-10000	0	-1.2	218	218
alpha5/beta1 Integrin	-0.002	0.023	-10000	0	-0.36	2	2
FGF2	-0.058	0.17	-10000	0	-0.5	61	61
STAT5A (dimer)	-0.37	0.46	-10000	0	-0.85	216	216
mol:L-citrulline	-0.29	0.37	-10000	0	-0.68	218	218
AGTR1	-0.15	0.24	-10000	0	-0.5	145	145
MAPK14	-0.55	0.67	-10000	0	-1.2	218	218
Tie2/SHP2	-0.47	0.55	-10000	0	-1.1	194	194
TEK	-0.51	0.62	-10000	0	-1.2	194	194
RPS6KB1	-0.39	0.49	-10000	0	-0.91	218	218
Angiotensin II/AT1	-0.1	0.17	-10000	0	-0.36	145	145
Tie2/Ang1/GRB2	-0.54	0.69	-10000	0	-1.2	218	218
MAPK3	-0.46	0.59	-10000	0	-1.1	218	218
MAPK1	-0.46	0.59	-10000	0	-1.1	218	218
Tie2/Ang1/GRB7	-0.55	0.69	-10000	0	-1.2	218	218
NFKB1	0.01	0	-10000	0	-10000	0	0
MAPK8	-0.52	0.66	-10000	0	-1.2	218	218
PI3K	-0.49	0.61	-10000	0	-1.1	218	218
FES	-0.55	0.67	-10000	0	-1.2	218	218
Crk/Dok-R	-0.54	0.61	-10000	0	-1.2	218	218
Tie2/Ang1/ABIN2	-0.54	0.69	-10000	0	-1.2	218	218
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.36	0.45	-10000	0	-0.83	218	218
STAT5A	0.009	0.024	-10000	0	-0.5	1	1
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.39	0.49	-10000	0	-0.91	218	218
Tie2/Ang2	-0.47	0.57	-10000	0	-1.1	217	217
Tie2/Ang1	-0.58	0.75	-10000	0	-1.3	218	218
FOXO1	-0.36	0.46	-10000	0	-0.84	218	218
ELF1	-0.028	0.051	-10000	0	-10000	0	0
ELF2	-0.53	0.67	-10000	0	-1.2	218	218
mol:Choline	-0.49	0.62	-10000	0	-1.1	218	218
cell migration	-0.11	0.12	-10000	0	-0.24	218	218
FYN	-0.38	0.46	-10000	0	-0.85	217	217
DOK2	-0.032	0.14	-10000	0	-0.5	38	38
negative regulation of cell cycle	-0.25	0.32	-10000	0	-0.58	216	216
ETS1	-0.045	0.1	-10000	0	-0.53	1	1
PXN	-0.31	0.4	-10000	0	-0.73	218	218
ITGB1	0.01	0	-10000	0	-10000	0	0
NOS3	-0.34	0.43	-10000	0	-0.79	218	218
RAC1	0.01	0	-10000	0	-10000	0	0
TNF	-0.064	0.14	-10000	0	-0.55	19	19
MAPKKK cascade	-0.49	0.62	-10000	0	-1.1	218	218
RASA1	0.01	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.56	0.68	-10000	0	-1.2	218	218
NCK1	0.01	0	-10000	0	-10000	0	0
vasculogenesis	-0.25	0.33	-10000	0	-0.6	218	218
mol:Phosphatidic acid	-0.49	0.62	-10000	0	-1.1	218	218
mol:Angiotensin II	0.001	0.002	-10000	0	-10000	0	0
mol:NADP	-0.29	0.37	-10000	0	-0.68	218	218
Rac1/GTP	-0.39	0.42	-10000	0	-0.84	218	218
MMP2	-0.52	0.66	-10000	0	-1.2	218	218

×

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	-0.44	0.54	-9999	-1	154	154
PLK1	-0.15	0.2	-9999	-10000	0	0
BIRC5	-0.19	0.2	-9999	-10000	0	0
HSPA1B	-0.44	0.54	-9999	-1	154	154
MAP2K1	-0.002	0.034	-9999	-10000	0	0
BRCA2	-0.44	0.54	-9999	-1	160	160
FOXM1	-0.57	0.7	-9999	-1.3	190	190
XRCC1	-0.44	0.54	-9999	-1	165	165
FOXM1B/p19	-0.51	0.49	-9999	-1	179	179
Cyclin D1/CDK4	-0.44	0.5	-9999	-0.98	163	163
CDC2	-0.47	0.57	-9999	-1.1	190	190
TGFA	-0.42	0.5	-9999	-0.95	163	163
SKP2	-0.44	0.54	-9999	-1	165	165
CCNE1	-0.19	0.26	-9999	-0.53	173	173
CKS1B	-0.44	0.55	-9999	-1.1	152	152
RB1	-0.22	0.18	-9999	-0.45	77	77
FOXM1C/SP1	-0.5	0.61	-9999	-1.2	178	178
AURKB	-0.17	0.2	-9999	-10000	0	0
CENPF	-0.5	0.59	-9999	-1.1	192	192
CDK4	0.001	0.051	-9999	-0.53	4	4
MYC	-0.38	0.48	-9999	-0.9	165	165
CHEK2	-0.009	0.072	-9999	-0.56	6	6
ONECUT1	-0.48	0.54	-9999	-1	176	176
CDKN2A	-0.15	0.24	-9999	-0.51	142	142
LAMA4	-0.45	0.55	-9999	-1	167	167
FOXM1B/HNF6	-0.56	0.64	-9999	-1.2	177	177
FOS	-0.46	0.57	-9999	-1.1	164	164
SP1	0.01	0.001	-9999	-10000	0	0
CDC25B	-0.44	0.54	-9999	-1	165	165
response to radiation	-0.013	0.031	-9999	-10000	0	0
CENPB	-0.44	0.54	-9999	-1	165	165
CENPA	-0.52	0.6	-9999	-1.1	197	197
NEK2	-0.52	0.6	-9999	-1.1	199	199
HIST1H2BA	-0.45	0.54	-9999	-1	167	167
CCNA2	-0.13	0.23	-9999	-0.53	119	119
EP300	0.01	0	-9999	-10000	0	0
CCNB1/CDK1	-0.52	0.64	-9999	-1.2	172	172
CCNB2	-0.5	0.6	-9999	-1.1	190	190
CCNB1	-0.49	0.59	-9999	-1.1	172	172
ETV5	-0.45	0.55	-9999	-1	166	166
ESR1	-0.45	0.56	-9999	-1.1	169	169
CCND1	-0.45	0.52	-9999	-1	164	164
GSK3A	0.002	0.028	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	-0.18	0.26	-9999	-0.45	205	205
CDK2	0.006	0.008	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.016	0.038	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.55	0.5	-9999	-1.1	190	190
GAS1	-0.45	0.56	-9999	-1	168	168
MMP2	-0.44	0.54	-9999	-1	165	165
RB1/FOXM1C	-0.48	0.55	-9999	-1.1	177	177
CREBBP	0.01	0	-9999	-10000	0	0

×

Aurora B 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
Condensin I complex	-0.15	0.17	-9999	-0.33	199	199
STMN1	-0.18	0.19	-9999	-0.36	247	247
Aurora B/RasGAP/Survivin	-0.31	0.27	-9999	-0.5	295	295
Chromosomal passenger complex/Cul3 protein complex	-0.13	0.14	-9999	-0.3	152	152
BIRC5	-0.3	0.26	-9999	-0.52	273	273
DES	-0.41	0.37	-9999	-0.74	250	250
Aurora C/Aurora B/INCENP	-0.14	0.14	-9999	-0.27	250	250
Aurora B/TACC1	-0.17	0.17	-9999	-0.32	253	253
Aurora B/PP2A	-0.18	0.18	-9999	-0.36	247	247
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.033	0.044	-9999	-10000	0	0
mitotic metaphase/anaphase transition	-0.003	0.004	-9999	-10000	0	0
NDC80	-0.34	0.32	-9999	-0.59	276	276
Cul3 protein complex	-0.013	0.063	-9999	-0.31	20	20
KIF2C	-0.12	0.11	-9999	-0.22	249	249
PEBP1	0.004	0.005	-9999	-10000	0	0
KIF20A	-0.28	0.26	-9999	-0.52	261	261
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.18	0.18	-9999	-0.36	247	247
SEPT1	0.009	0.024	-9999	-0.5	1	1
SMC2	0.01	0	-9999	-10000	0	0
SMC4	0.01	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.063	0.074	-9999	-10000	0	0
PSMA3	0.01	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.002	0.003	-9999	-10000	0	0
H3F3B	-0.089	0.099	-9999	-0.18	247	247
AURKB	-0.27	0.26	-9999	-0.52	247	247
AURKC	0.005	0.047	-9999	-0.5	4	4
CDCA8	-0.18	0.25	-9999	-0.53	161	161
cytokinesis	-0.23	0.2	-9999	-0.44	202	202
Aurora B/Septin1	-0.21	0.2	-9999	-0.44	180	180
AURKA	-0.095	0.21	-9999	-0.52	93	93
INCENP	0.003	0.007	-9999	-10000	0	0
KLHL13	-0.01	0.099	-9999	-0.5	18	18
BUB1	-0.14	0.24	-9999	-0.52	129	129
hSgo1/Aurora B/Survivin	-0.42	0.36	-9999	-0.65	301	301
EVI5	0.009	0.002	-9999	-10000	0	0
RhoA/GTP	-0.22	0.22	-9999	-0.47	173	173
SGOL1	-0.24	0.26	-9999	-0.51	225	225
CENPA	-0.16	0.16	-9999	-0.3	242	242
NCAPG	-0.23	0.26	-9999	-0.51	214	214
Aurora B/HC8 Proteasome	-0.18	0.18	-9999	-0.36	247	247
NCAPD2	0.009	0.024	-9999	-0.51	1	1
Aurora B/PP1-gamma	-0.18	0.18	-9999	-0.36	247	247
RHOA	0.01	0	-9999	-10000	0	0
NCAPH	-0.22	0.26	-9999	-0.51	207	207
NPM1	-0.084	0.081	-9999	-10000	0	0
RASA1	0.01	0	-9999	-10000	0	0
KLHL9	0.007	0.041	-9999	-0.5	3	3
mitotic prometaphase	-0.009	0.008	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.18	0.18	-9999	-0.36	247	247
PPP1CC	0.01	0	-9999	-10000	0	0
Centraspindlin	-0.24	0.24	-9999	-0.49	191	191
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.084	0.081	-9999	-10000	0	0
MYLK	-0.099	0.12	-9999	-0.2	238	238
KIF23	-0.11	0.22	-9999	-0.52	104	104
VIM	-0.18	0.19	-9999	-0.36	247	247
RACGAP1	0	0.055	-9999	-0.52	5	5
mitosis	0	0	-9999	-10000	0	0
NCL	-0.084	0.081	-9999	-10000	0	0
Chromosomal passenger complex	-0.2	0.19	-9999	-0.37	238	238
Chromosomal passenger complex/EVI5	-0.34	0.32	-9999	-0.62	238	238
TACC1	-0.012	0.1	-9999	-0.5	20	20
PPP2R5D	0.01	0	-9999	-10000	0	0
CUL3	0.01	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.21	0.25	-10000	0	-0.66	81	81
IHH	-0.3	0.27	-10000	0	-0.54	263	263
SHH Np/Cholesterol/GAS1	-0.04	0.099	-10000	0	-0.28	68	68
LRPAP1	0.01	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.04	0.099	0.27	68	-10000	0	68
SMO/beta Arrestin2	-0.21	0.22	-10000	0	-0.51	93	93
SMO	-0.22	0.23	-10000	0	-0.53	96	96
AKT1	-0.091	0.11	-10000	0	-0.34	10	10
ARRB2	0.01	0	-10000	0	-10000	0	0
BOC	0.008	0.034	-10000	0	-0.51	2	2
ADRBK1	0.01	0	-10000	0	-10000	0	0
heart looping	-0.22	0.22	-10000	0	-0.52	97	97
STIL	-0.19	0.22	-10000	0	-0.52	107	107
DHH N/PTCH2	-0.029	0.098	-10000	0	-0.35	39	39
DHH N/PTCH1	-0.19	0.2	-10000	0	-0.49	91	91
PIK3CA	0.01	0	-10000	0	-10000	0	0
DHH	-0.032	0.14	-10000	0	-0.5	38	38
PTHLH	-0.27	0.29	-10000	0	-0.78	81	81
determination of left/right symmetry	-0.22	0.22	-10000	0	-0.52	97	97
PIK3R1	0.009	0.024	-10000	0	-0.5	1	1
skeletal system development	-0.27	0.29	-10000	0	-0.77	81	81
IHH N/Hhip	-0.37	0.26	-10000	0	-0.5	352	352
DHH N/Hhip	-0.22	0.2	-10000	0	-0.38	267	267
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.22	0.22	-10000	0	-0.52	97	97
pancreas development	-0.27	0.25	-10000	0	-0.5	256	256
HHAT	0.008	0.033	-10000	0	-0.5	2	2
PI3K	-0.001	0.016	-10000	0	-0.35	1	1
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.004	0.084	-10000	0	-0.5	13	13
somite specification	-0.22	0.22	-10000	0	-0.52	97	97
SHH Np/Cholesterol/PTCH1	-0.17	0.2	-10000	0	-0.47	100	100
SHH Np/Cholesterol/PTCH2	-0.033	0.088	-10000	0	-0.26	59	59
SHH Np/Cholesterol/Megalin	-0.1	0.15	-10000	0	-0.3	165	165
SHH	-0.029	0.12	-10000	0	-0.35	58	58
catabolic process	-0.2	0.2	-10000	0	-0.52	73	73
SMO/Vitamin D3	-0.2	0.22	-10000	0	-0.51	100	100
SHH Np/Cholesterol/Hhip	-0.18	0.16	-10000	0	-0.3	275	275
LRP2	-0.13	0.23	-10000	0	-0.5	126	126
receptor-mediated endocytosis	-0.25	0.23	-10000	0	-0.52	158	158
SHH Np/Cholesterol/BOC	-0.034	0.088	-10000	0	-0.26	60	60
SHH Np/Cholesterol/CDO	-0.039	0.097	-10000	0	-0.27	67	67
mesenchymal cell differentiation	0.18	0.16	0.3	275	-10000	0	275
mol:Vitamin D3	-0.17	0.2	-10000	0	-0.47	100	100
IHH N/PTCH2	-0.17	0.17	-10000	0	-0.32	263	263
CDON	-0.002	0.077	-10000	0	-0.5	11	11
IHH N/PTCH1	-0.2	0.2	-10000	0	-0.53	73	73
Megalin/LRPAP1	-0.095	0.16	-10000	0	-0.35	126	126
PTCH2	0.009	0.024	-10000	0	-0.5	1	1
SHH Np/Cholesterol	-0.034	0.089	-10000	0	-0.27	58	58
PTCH1	-0.2	0.2	-10000	0	-0.52	73	73
HHIP	-0.27	0.25	-10000	0	-0.5	256	256

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.01	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.15	0.14	-9999	-0.27	250	250
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.042	0.039	-9999	-10000	0	0
AURKB	-0.27	0.26	-9999	-0.51	247	247
AURKC	0.005	0.047	-9999	-0.5	4	4

×

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	-0.054	0.2	0.26	1	-0.45	60	61
PTK2B	0.008	0.033	-10000	0	-0.5	2	2
mol:Ca2+	-0.053	0.28	-10000	0	-0.94	36	36
EDN1	-0.071	0.23	0.21	1	-0.54	76	77
EDN3	-0.13	0.22	-10000	0	-0.5	127	127
EDN2	-0.14	0.24	-10000	0	-0.51	133	133
HRAS/GDP	-0.085	0.2	-10000	0	-0.46	67	67
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.008	0.13	-10000	0	-0.34	36	36
ADCY4	-0.07	0.17	-10000	0	-0.48	45	45
ADCY5	-0.092	0.2	-10000	0	-0.52	60	60
ADCY6	-0.058	0.16	-10000	0	-0.45	43	43
ADCY7	-0.059	0.16	-10000	0	-0.46	42	42
ADCY1	-0.063	0.17	-10000	0	-0.45	46	46
ADCY2	-0.084	0.18	-10000	0	-0.48	53	53
ADCY3	-0.058	0.16	-10000	0	-0.47	38	38
ADCY8	-0.17	0.19	-10000	0	-0.44	100	100
ADCY9	-0.063	0.17	-10000	0	-0.46	43	43
arachidonic acid secretion	-0.072	0.2	-10000	0	-0.5	61	61
ETB receptor/Endothelin-1/Gq/GTP	-0.16	0.2	-10000	0	-0.36	171	171
GNAO1	0.004	0.053	-10000	0	-0.51	5	5
HRAS	0.009	0.002	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	0.02	0.22	0.23	157	-0.48	39	196
ETA receptor/Endothelin-1/Gs/GTP	0.011	0.22	0.21	155	-0.41	65	220
mol:GTP	0	0.005	-10000	0	-10000	0	0
COL3A1	-0.11	0.26	-10000	0	-0.49	119	119
EDNRB	-0.29	0.25	-10000	0	-0.5	276	276
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.063	0.22	-10000	0	-0.64	37	37
CYSLTR1	-0.067	0.23	-10000	0	-0.66	39	39
SLC9A1	-0.025	0.11	0.18	1	-0.29	32	33
mol:GDP	-0.097	0.22	-10000	0	-0.46	81	81
SLC9A3	-0.31	0.36	-10000	0	-0.54	281	281
RAF1	-0.095	0.21	-10000	0	-0.52	60	60
JUN	-0.022	0.2	-10000	0	-0.68	24	24
JAK2	-0.054	0.2	0.26	1	-0.45	61	62
mol:IP3	-0.095	0.18	-10000	0	-0.38	85	85
ETA receptor/Endothelin-1	-0.03	0.28	0.26	158	-0.51	67	225
PLCB1	0.008	0.024	-10000	0	-0.51	1	1
PLCB2	-0.001	0.074	-10000	0	-0.5	10	10
ETA receptor/Endothelin-3	-0.096	0.18	-10000	0	-0.37	129	129
FOS	-0.092	0.26	-10000	0	-0.89	36	36
Gai/GDP	-0.011	0.085	-10000	0	-0.58	3	3
CRK	0.01	0.001	-10000	0	-10000	0	0
mol:Ca ++	-0.15	0.26	-10000	0	-0.56	98	98
BCAR1	0.009	0.024	-10000	0	-0.5	1	1
PRKCB1	-0.091	0.18	-10000	0	-0.37	84	84
GNAQ	0.009	0.024	-10000	0	-0.5	1	1
GNAZ	-0.035	0.14	-10000	0	-0.5	41	41
GNAL	-0.002	0.078	-10000	0	-0.5	11	11
Gs family/GDP	-0.12	0.17	-10000	0	-0.44	74	74
ETA receptor/Endothelin-1/Gq/GTP	-0.012	0.14	0.2	1	-0.36	41	42
MAPK14	-0.13	0.18	-10000	0	-0.37	109	109
TRPC6	-0.059	0.3	-10000	0	-1	36	36
GNAI2	0.01	0	-10000	0	-10000	0	0
GNAI3	0.01	0	-10000	0	-10000	0	0
GNAI1	0.008	0.033	-10000	0	-0.5	2	2
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.14	0.19	-10000	0	-0.37	131	131
ETB receptor/Endothelin-2	-0.3	0.23	-10000	0	-0.44	324	324
ETB receptor/Endothelin-3	-0.3	0.23	-10000	0	-0.43	323	323
ETB receptor/Endothelin-1	-0.26	0.26	-10000	0	-0.45	282	282
MAPK3	-0.098	0.26	-10000	0	-0.78	44	44
MAPK1	-0.098	0.26	-10000	0	-0.78	44	44
Rac1/GDP	-0.085	0.2	-10000	0	-0.46	66	66
cAMP biosynthetic process	-0.1	0.19	-10000	0	-0.47	68	68
MAPK8	-0.032	0.2	-10000	0	-0.6	38	38
SRC	0.01	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.15	0.18	-10000	0	-0.38	125	125
p130Cas/CRK/Src/PYK2	-0.094	0.23	-10000	0	-0.57	62	62
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.085	0.2	-10000	0	-0.46	67	67
COL1A2	-0.21	0.28	-10000	0	-0.62	111	111
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.1	0.19	-10000	0	-0.38	135	135
mol:DAG	-0.095	0.18	-10000	0	-0.38	85	85
MAP2K2	-0.092	0.22	-10000	0	-0.62	50	50
MAP2K1	-0.092	0.22	-10000	0	-0.62	51	51
EDNRA	0.007	0.11	-10000	0	-0.37	9	9
positive regulation of muscle contraction	-0.039	0.17	-10000	0	-0.48	33	33
Gq family/GDP	-0.077	0.17	-10000	0	-0.48	48	48
HRAS/GTP	-0.1	0.2	-10000	0	-0.43	81	81
PRKCH	-0.085	0.17	-10000	0	-0.46	48	48
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCA	-0.086	0.18	-10000	0	-0.46	48	48
PRKCB	-0.091	0.19	-10000	0	-0.45	64	64
PRKCE	-0.087	0.18	-10000	0	-0.38	80	80
PRKCD	-0.085	0.18	-10000	0	-0.45	49	49
PRKCG	-0.11	0.19	-10000	0	-0.46	69	69
regulation of vascular smooth muscle contraction	-0.11	0.3	-10000	0	-1.1	36	36
PRKCQ	-0.12	0.21	-10000	0	-0.43	110	110
PLA2G4A	-0.08	0.22	-10000	0	-0.55	61	61
GNA14	-0.005	0.088	-10000	0	-0.51	14	14
GNA15	0.01	0.004	-10000	0	-10000	0	0
GNA12	0.01	0	-10000	0	-10000	0	0
GNA11	0.008	0.033	-10000	0	-0.5	2	2
Rac1/GTP	0.02	0.22	0.23	157	-0.48	39	196
MMP1	-0.22	0.2	-10000	0	-0.38	260	260

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0.06	0.071	0.13	225	-10000	0	225
BUB1B	-0.12	0.12	-10000	0	-0.2	287	287
PLK1	-0.025	0.049	-10000	0	-0.11	86	86
PLK1S1	-0.009	0.026	-10000	0	-0.11	1	1
KIF2A	-0.016	0.045	-10000	0	-0.18	1	1
regulation of mitotic centrosome separation	-0.025	0.049	-10000	0	-0.11	86	86
GOLGA2	0.01	0	-10000	0	-10000	0	0
Hec1/SPC24	-0.22	0.25	-10000	0	-0.44	246	246
WEE1	-0.022	0.054	-10000	0	-10000	0	0
cytokinesis	-0.11	0.13	-10000	0	-0.24	204	204
PP2A-alpha B56	-0.014	0.034	-10000	0	-10000	0	0
AURKA	-0.019	0.044	-10000	0	-0.1	86	86
PICH/PLK1	-0.14	0.22	-10000	0	-0.41	173	173
CENPE	-0.077	0.15	-10000	0	-0.35	101	101
RhoA/GTP	0	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.016	0.044	-10000	0	-0.18	1	1
PPP2CA	0.01	0	-10000	0	-10000	0	0
FZR1	0.01	0	-10000	0	-10000	0	0
TPX2	-0.044	0.051	-10000	0	-0.1	148	148
PAK1	0.008	0.004	-10000	0	-10000	0	0
SPC24	-0.15	0.24	-10000	0	-0.51	141	141
FBXW11	0.01	0	-10000	0	-10000	0	0
CLSPN	-0.038	0.058	-10000	0	-0.13	88	88
GORASP1	0.01	0	-10000	0	-10000	0	0
metaphase	-0.002	0.004	-10000	0	-0.011	85	85
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	-0.013	0.026	-10000	0	-0.059	77	77
G2 phase of mitotic cell cycle	-0.001	0.003	-10000	0	-0.013	1	1
STAG2	0.01	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	-0.001	0.011	-10000	0	-10000	0	0
spindle elongation	-0.025	0.049	-10000	0	-0.11	86	86
ODF2	0.008	0.004	-10000	0	-10000	0	0
BUB1	-0.023	0.04	-10000	0	-10000	0	0
TPT1	-0.009	0.026	-10000	0	-0.11	1	1
CDC25C	-0.064	0.06	-10000	0	-0.13	109	109
CDC25B	0.008	0.003	-10000	0	-10000	0	0
SGOL1	-0.061	0.071	-10000	0	-0.13	225	225
RHOA	0.01	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.067	0.11	-10000	0	-0.25	99	99
CDC14B	0.007	0.004	-10000	0	-10000	0	0
CDC20	-0.3	0.26	-10000	0	-0.51	277	277
PLK1/PBIP1	-0.046	0.088	-10000	0	-0.34	35	35
mitosis	-0.003	0.008	0.02	16	-0.018	77	93
FBXO5	-0.016	0.043	-10000	0	-0.17	1	1
CDC2	-0.003	0.005	-10000	0	-0.011	102	102
NDC80	-0.25	0.26	-10000	0	-0.51	235	235
metaphase plate congression	-0.014	0.032	-10000	0	-10000	0	0
ERCC6L	-0.14	0.19	-10000	0	-0.4	151	151
NLP/gamma Tubulin	-0.011	0.027	-10000	0	-0.11	2	2
microtubule cytoskeleton organization	-0.009	0.026	-10000	0	-0.11	1	1
G2/M transition DNA damage checkpoint	-0.001	0.002	-10000	0	-0.01	1	1
PPP1R12A	0.009	0.001	-10000	0	-10000	0	0
interphase	-0.001	0.002	-10000	0	-0.01	1	1
PLK1/PRC1-2	-0.2	0.22	-10000	0	-0.37	261	261
GRASP65/GM130/RAB1/GTP/PLK1	-0.017	0.027	-10000	0	-10000	0	0
RAB1A	0.01	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	-0.015	0.046	-10000	0	-0.36	1	1
mitotic prometaphase	-0.003	0.003	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.039	0.035	-10000	0	-10000	0	0
microtubule-based process	-0.17	0.17	-10000	0	-0.32	261	261
Golgi organization	-0.025	0.049	-10000	0	-0.11	86	86
Cohesin/SA2	-0.028	0.036	-10000	0	-0.17	1	1
PPP1CB/MYPT1	0	0	-10000	0	-10000	0	0
KIF20A	-0.28	0.26	-10000	0	-0.51	261	261
APC/C/CDC20	-0.18	0.17	-10000	0	-0.32	277	277
PPP2R1A	0.01	0	-10000	0	-10000	0	0
chromosome segregation	-0.046	0.087	-10000	0	-0.33	35	35
PRC1	-0.068	0.19	-10000	0	-0.51	70	70
ECT2	-0.033	0.092	-10000	0	-0.35	29	29
C13orf34	-0.015	0.044	-10000	0	-0.36	1	1
NUDC	-0.014	0.032	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.12	0.12	-10000	0	-0.2	287	287
spindle assembly	-0.018	0.04	-10000	0	-0.089	70	70
spindle stabilization	-0.009	0.026	-10000	0	-0.11	1	1
APC/C/HCDH1	0.012	0.005	-10000	0	-10000	0	0
MKLP2/PLK1	-0.17	0.17	-10000	0	-0.32	261	261
CCNB1	-0.14	0.24	-10000	0	-0.51	133	133
PPP1CB	0.009	0.001	-10000	0	-10000	0	0
BTRC	0.01	0	-10000	0	-10000	0	0
ROCK2	-0.008	0.038	-10000	0	-0.4	1	1
TUBG1	-0.009	0.026	-10000	0	-0.11	2	2
G2/M transition of mitotic cell cycle	-0.067	0.1	-10000	0	-0.24	99	99
MLF1IP	-0.024	0.1	-10000	0	-0.38	35	35
INCENP	0.009	0.001	-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	-0.33	0.47	-9999	-1.1	87	87
HDAC7	0.008	0.007	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.28	0.36	-9999	-0.84	85	85
SMAD4	0.011	0.003	-9999	-10000	0	0
ID2	-0.33	0.47	-9999	-1.1	87	87
AP1	-0.029	0.095	-9999	-0.36	35	35
ABCG2	-0.36	0.49	-9999	-1.1	92	92
HIF1A	-0.041	0.071	-9999	-10000	0	0
TFF3	-0.39	0.51	-9999	-1.1	110	110
GATA2	-0.037	0.15	-9999	-0.51	41	41
AKT1	-0.046	0.08	-9999	-10000	0	0
response to hypoxia	-0.063	0.084	-9999	-0.25	7	7
MCL1	-0.33	0.47	-9999	-1.1	87	87
NDRG1	-0.33	0.47	-9999	-1.1	87	87
SERPINE1	-0.34	0.47	-9999	-1.1	88	88
FECH	-0.33	0.47	-9999	-1.1	88	88
FURIN	-0.34	0.48	-9999	-1.1	88	88
NCOA2	0.006	0.047	-9999	-0.5	4	4
EP300	-0.047	0.12	-9999	-0.35	11	11
HMOX1	-0.33	0.47	-9999	-1.1	87	87
BHLHE40	-0.33	0.47	-9999	-1.1	87	87
BHLHE41	-0.34	0.48	-9999	-1.1	90	90
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.04	0.07	-9999	-0.4	4	4
ENG	-0.012	0.11	-9999	-0.58	6	6
JUN	0.004	0.048	-9999	-0.5	4	4
RORA	-0.34	0.47	-9999	-1.1	88	88
ABCB1	-0.12	0.25	-9999	-1.2	21	21
TFRC	-0.34	0.47	-9999	-1.1	88	88
CXCR4	-0.33	0.47	-9999	-1.1	87	87
TF	-0.39	0.52	-9999	-1.1	111	111
CITED2	-0.33	0.47	-9999	-1.1	87	87
HIF1A/ARNT	-0.38	0.55	-9999	-1.2	99	99
LDHA	-0.046	0.059	-9999	-0.45	1	1
ETS1	-0.33	0.47	-9999	-1.1	87	87
PGK1	-0.33	0.47	-9999	-1.1	87	87
NOS2	-0.36	0.49	-9999	-1.1	104	104
ITGB2	-0.34	0.47	-9999	-1.1	89	89
ALDOA	-0.33	0.47	-9999	-1.1	87	87
Cbp/p300/CITED2	-0.33	0.48	-9999	-1.1	80	80
FOS	-0.026	0.13	-9999	-0.51	31	31
HK2	-0.34	0.47	-9999	-1.1	90	90
SP1	0.015	0.014	-9999	-10000	0	0
GCK	-0.11	0.27	-9999	-1.3	14	14
HK1	-0.33	0.47	-9999	-1.1	87	87
NPM1	-0.33	0.47	-9999	-1.1	87	87
EGLN1	-0.33	0.47	-9999	-1.1	88	88
CREB1	0.016	0.001	-9999	-10000	0	0
PGM1	-0.33	0.47	-9999	-1.1	87	87
SMAD3	0.011	0.003	-9999	-10000	0	0
EDN1	-0.21	0.45	-9999	-1.2	78	78
IGFBP1	-0.37	0.49	-9999	-1.1	100	100
VEGFA	-0.25	0.36	-9999	-0.78	73	73
HIF1A/JAB1	-0.025	0.032	-9999	-10000	0	0
CP	-0.45	0.52	-9999	-1.1	132	132
CXCL12	-0.35	0.48	-9999	-1.1	93	93
COPS5	0.01	0.001	-9999	-10000	0	0
SMAD3/SMAD4	0	0.004	-9999	-10000	0	0
BNIP3	-0.33	0.47	-9999	-1.1	87	87
EGLN3	-0.39	0.52	-9999	-1.1	112	112
CA9	-0.49	0.51	-9999	-1.1	135	135
TERT	-0.4	0.52	-9999	-1.1	107	107
ENO1	-0.33	0.47	-9999	-1.1	87	87
PFKL	-0.33	0.47	-9999	-1.1	87	87
NCOA1	0.01	0	-9999	-10000	0	0
ADM	-0.34	0.47	-9999	-1.1	87	87
ARNT	-0.041	0.071	-9999	-10000	0	0
HNF4A	-0.1	0.22	-9999	-0.51	102	102
ADFP	-0.34	0.47	-9999	-1	96	96
SLC2A1	-0.33	0.42	-9999	-0.88	114	114
LEP	-0.36	0.48	-9999	-1.1	95	95
HIF1A/ARNT/Cbp/p300	-0.29	0.38	-9999	-0.86	91	91
EPO	-0.15	0.27	-9999	-0.76	6	6
CREBBP	-0.047	0.12	-9999	-0.35	11	11
HIF1A/ARNT/Cbp/p300/HDAC7	-0.31	0.39	-9999	-0.91	87	87
PFKFB3	-0.34	0.47	-9999	-1.1	87	87
NT5E	-0.35	0.47	-9999	-1.1	93	93

×

Visual signal transduction: Cones

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	-0.021	0.071	-9999	-0.26	39	39
RGS9BP	-0.067	0.18	-9999	-0.5	70	70
mol:GTP	0	0	-9999	-10000	0	0
GRK1	-0.026	0.12	-9999	-0.51	28	28
mol:Na +	-0.16	0.18	-9999	-0.34	216	216
mol:ADP	-0.013	0.091	-9999	-0.37	29	29
GNAT2	0.007	0.024	-9999	-0.51	1	1
RGS9-1/Gbeta5/R9AP	-0.14	0.17	-9999	-0.33	195	195
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.001	0.02	-9999	-0.31	2	2
GRK7	0.005	0.024	-9999	-0.51	1	1
CNGB3	-0.092	0.2	-9999	-0.51	87	87
Cone Metarhodopsin II/X-Arrestin	-0.002	0.024	-9999	-0.37	2	2
mol:Ca2+	-0.16	0.18	-9999	-0.32	239	239
Cone PDE6	-0.12	0.15	-9999	-0.5	25	25
Cone Metarhodopsin II	-0.017	0.068	-9999	-0.28	29	29
Na + (4 Units)	-0.16	0.18	-9999	-0.32	239	239
GNAT2/GDP	-0.11	0.15	-9999	-0.49	25	25
GNB5	0.01	0	-9999	-10000	0	0
mol:GMP (4 units)	0.008	0.019	-9999	-0.28	2	2
Cone Transducin	-0.023	0.075	-9999	-0.27	39	39
SLC24A2	-0.037	0.14	-9999	-0.51	39	39
GNB3/GNGT2	-0.029	0.099	-9999	-0.36	38	38
GNB3	-0.025	0.13	-9999	-0.51	31	31
GNAT2/GTP	-0.001	0.017	-9999	-0.37	1	1
CNGA3	-0.16	0.25	-9999	-0.51	156	156
ARR3	0	0.034	-9999	-0.51	2	2
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.16	0.18	-9999	-0.35	216	216
mol:Pi	-0.14	0.17	-9999	-0.32	195	195
Cone CNG Channel	-0.13	0.15	-9999	-0.51	28	28
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.037	0.14	-9999	-0.51	39	39
RGS9	-0.15	0.24	-9999	-0.5	149	149
PDE6C	0.003	0.004	-9999	-10000	0	0
GNGT2	0.002	0.062	-9999	-0.5	7	7
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.001	0.024	-9999	-0.51	1	1

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	-0.1	0.33	-9999	-1	48	48
MKNK1	0.01	0	-9999	-10000	0	0
MAPK14	-0.033	0.12	-9999	-0.29	81	81
ATF2/c-Jun	-0.017	0.12	-9999	-0.55	10	10
MAPK11	-0.036	0.13	-9999	-0.47	12	12
MITF	-0.038	0.16	-9999	-0.36	84	84
MAPKAPK5	-0.033	0.15	-9999	-0.34	84	84
KRT8	-0.034	0.15	-9999	-0.35	84	84
MAPKAPK3	0.01	0	-9999	-10000	0	0
MAPKAPK2	0.01	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.051	0.18	-9999	-0.43	84	84
CEBPB	-0.033	0.15	-9999	-0.34	84	84
SLC9A1	-0.033	0.15	-9999	-0.34	84	84
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.028	0.15	-9999	-0.34	84	84
p38alpha-beta/MNK1	-0.032	0.15	-9999	-0.51	12	12
JUN	-0.016	0.12	-9999	-0.54	10	10
PPARGC1A	-0.12	0.22	-9999	-0.47	85	85
USF1	-0.033	0.15	-9999	-0.34	84	84
RAB5/GDP/GDI1	-0.046	0.097	-9999	-0.37	12	12
NOS2	-0.094	0.32	-9999	-1	43	43
DDIT3	-0.033	0.15	-9999	-0.34	84	84
RAB5A	0.01	0	-9999	-10000	0	0
HSPB1	-0.021	0.13	-9999	-0.44	13	13
p38alpha-beta/HBP1	-0.032	0.15	-9999	-0.51	12	12
CREB1	-0.034	0.16	-9999	-0.37	84	84
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	-0.022	0.13	-9999	-0.45	12	12
RPS6KA4	-0.033	0.15	-9999	-0.34	84	84
PLA2G4A	-0.061	0.16	-9999	-0.51	21	21
GDI1	-0.033	0.15	-9999	-0.34	84	84
TP53	-0.044	0.18	-9999	-0.42	84	84
RPS6KA5	-0.035	0.15	-9999	-0.35	84	84
ESR1	-0.049	0.18	-9999	-0.38	90	90
HBP1	0.01	0	-9999	-10000	0	0
MEF2C	-0.033	0.15	-9999	-0.34	84	84
MEF2A	-0.033	0.15	-9999	-0.34	84	84
EIF4EBP1	-0.035	0.16	-9999	-0.37	84	84
KRT19	-0.036	0.15	-9999	-0.34	84	84
ELK4	-0.033	0.15	-9999	-0.34	84	84
ATF6	-0.033	0.15	-9999	-0.34	84	84
ATF1	-0.034	0.16	-9999	-0.37	84	84
p38alpha-beta/MAPKAPK2	-0.032	0.15	-9999	-0.34	84	84
p38alpha-beta/MAPKAPK3	-0.032	0.15	-9999	-0.34	84	84

×

IL4-mediated signaling events

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
BCL2L1	-0.45	0.53	-10000	0	-1.2	115	115
STAT6 (cleaved dimer)	-0.49	0.5	-10000	0	-1.1	150	150
IGHG1	-0.14	0.17	-10000	0	-0.38	15	15
IGHG3	-0.44	0.51	-10000	0	-1.1	144	144
AKT1	-0.18	0.24	-10000	0	-0.75	13	13
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.13	0.2	-10000	0	-0.93	7	7
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.19	0.25	-10000	0	-0.88	10	10
THY1	-0.46	0.53	-10000	0	-1.2	116	116
MYB	0.003	0.058	-10000	0	-0.51	6	6
HMGA1	-0.042	0.16	-10000	0	-0.51	46	46
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.24	0.28	-10000	0	-0.64	76	76
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.19	0.25	-10000	0	-0.84	12	12
SP1	0.016	0.004	-10000	0	-10000	0	0
INPP5D	0.007	0.041	-10000	0	-0.5	3	3
SOCS5	0.021	0.014	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.47	0.49	-10000	0	-1.2	123	123
SOCS1	-0.27	0.34	-10000	0	-0.76	95	95
SOCS3	-0.2	0.26	-10000	0	-0.92	14	14
FCER2	-0.35	0.43	-10000	0	-0.99	90	90
PARP14	0.01	0.003	-10000	0	-10000	0	0
CCL17	-0.5	0.6	-10000	0	-1.4	124	124
GRB2	0.01	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.15	0.2	-10000	0	-0.73	8	8
T cell proliferation	-0.44	0.54	-10000	0	-1.2	115	115
IL4R/JAK1	-0.45	0.53	-10000	0	-1.2	117	117
EGR2	-0.47	0.57	-10000	0	-1.3	114	114
JAK2	-0.012	0.039	-10000	0	-0.54	1	1
JAK3	0.014	0.004	-10000	0	-10000	0	0
PIK3R1	0.009	0.024	-10000	0	-0.5	1	1
JAK1	0.006	0.011	-10000	0	-10000	0	0
COL1A2	-0.14	0.2	-10000	0	-0.72	14	14
CCL26	-0.47	0.54	-10000	0	-1.2	117	117
IL4R	-0.48	0.57	-10000	0	-1.3	116	116
PTPN6	0.02	0.013	-10000	0	-10000	0	0
IL13RA2	-0.5	0.58	-10000	0	-1.3	127	127
IL13RA1	-0.011	0.031	-10000	0	-10000	0	0
IRF4	-0.11	0.25	-10000	0	-1	22	22
ARG1	-0.12	0.19	-10000	0	-0.72	19	19
CBL	-0.22	0.27	-10000	0	-0.62	68	68
GTF3A	0.005	0.031	-10000	0	-0.51	1	1
PIK3CA	0.01	0	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.014	0.047	-10000	0	-0.4	1	1
IRF4/BCL6	-0.098	0.23	-10000	0	-0.96	22	22
CD40LG	-0.009	0.11	-10000	0	-0.5	22	22
MAPK14	-0.22	0.27	-10000	0	-0.64	57	57
mitosis	-0.17	0.24	-10000	0	-0.74	11	11
STAT6	-0.54	0.63	-10000	0	-1.4	127	127
SPI1	-0.014	0.11	-10000	0	-0.5	24	24
RPS6KB1	-0.16	0.23	-10000	0	-0.72	10	10
STAT6 (dimer)	-0.53	0.63	-10000	0	-1.4	127	127
STAT6 (dimer)/PARP14	-0.49	0.58	-10000	0	-1.3	119	119
mast cell activation	0.01	0.013	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.19	0.26	-10000	0	-0.79	25	25
FRAP1	-0.18	0.24	-10000	0	-0.75	13	13
LTA	-0.46	0.53	-10000	0	-1.2	114	114
FES	0.009	0.024	-10000	0	-0.5	1	1
T-helper 1 cell differentiation	0.51	0.61	1.3	129	-10000	0	129
CCL11	-0.46	0.54	-10000	0	-1.2	122	122
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.18	0.24	-10000	0	-0.87	10	10
IL2RG	0.009	0.052	-10000	0	-0.49	5	5
IL10	-0.46	0.54	-10000	0	-1.2	117	117
IRS1	0.009	0.024	-10000	0	-0.5	1	1
IRS2	0.009	0.024	-10000	0	-0.5	1	1
IL4	-0.097	0.12	-10000	0	-10000	0	0
IL5	-0.46	0.53	-10000	0	-1.2	116	116
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.36	0.4	-10000	0	-0.91	116	116
COL1A1	-0.23	0.24	-10000	0	-0.61	80	80
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.46	0.55	-10000	0	-1.3	113	113
IL2R gamma/JAK3	0.014	0.038	-10000	0	-0.34	5	5
TFF3	-0.5	0.57	-10000	0	-1.3	132	132
ALOX15	-0.78	0.74	-10000	0	-1.4	247	247
MYBL1	-0.002	0.079	-10000	0	-0.51	11	11
T-helper 2 cell differentiation	-0.36	0.41	-10000	0	-0.93	117	117
SHC1	0.01	0	-10000	0	-10000	0	0
CEBPB	0.013	0.006	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.18	0.24	-10000	0	-0.82	11	11
mol:PI-3-4-5-P3	-0.18	0.24	-10000	0	-0.75	13	13
PI3K	-0.18	0.26	-10000	0	-0.81	13	13
DOK2	-0.032	0.14	-10000	0	-0.5	38	38
ETS1	0.019	0.026	-10000	0	-0.46	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.14	0.19	-10000	0	-0.69	8	8
ITGB3	-0.46	0.54	-10000	0	-1.2	117	117
PIGR	-0.6	0.69	-10000	0	-1.5	154	154
IGHE	0.034	0.042	-10000	0	-10000	0	0
MAPKKK cascade	-0.14	0.19	-10000	0	-0.68	8	8
BCL6	0.01	0.003	-10000	0	-10000	0	0
OPRM1	-0.46	0.53	-10000	0	-1.2	115	115
RETNLB	-0.46	0.53	-10000	0	-1.2	115	115
SELP	-0.58	0.68	-10000	0	-1.5	148	148
AICDA	-0.47	0.55	-10000	0	-1.2	125	125

×

Signaling events regulated by Ret tyrosine kinase

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.033	0.042	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.085	0.12	-9999	-0.36	28	28
JUN	-0.053	0.12	-9999	-0.35	25	25
HRAS	0.01	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.12	0.16	-9999	-0.3	186	186
RAP1A	0.01	0	-9999	-10000	0	0
FRS2	0.008	0.034	-9999	-0.51	2	2
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.12	0.16	-9999	-0.3	186	186
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.01	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.085	0.13	-9999	-0.27	146	146
RHOA	0.01	0	-9999	-10000	0	0
RAP1A/GTP	-0.1	0.14	-9999	-0.48	25	25
GRB7	0.003	0.058	-9999	-0.51	6	6
RET51/GFRalpha1/GDNF	-0.12	0.16	-9999	-0.32	128	128
MAPKKK cascade	-0.096	0.13	-9999	-0.44	28	28
BCAR1	0.009	0.024	-9999	-0.5	1	1
RET9/GFRalpha1/GDNF/IRS1	-0.086	0.13	-9999	-0.28	146	146
lamellipodium assembly	-0.082	0.11	-9999	-0.34	28	28
RET51/GFRalpha1/GDNF/SHC	-0.12	0.16	-9999	-0.3	186	186
PIK3CA	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.085	0.13	-9999	-0.27	146	146
RET9/GFRalpha1/GDNF/Shank3	-0.089	0.14	-9999	-0.28	147	147
MAPK3	-0.078	0.14	-9999	-0.45	25	25
DOK1	0.01	0	-9999	-10000	0	0
DOK6	-0.04	0.15	-9999	-0.5	46	46
PXN	0.01	0	-9999	-10000	0	0
neurite development	-0.074	0.15	-9999	-0.37	55	55
DOK5	-0.071	0.19	-9999	-0.51	72	72
GFRA1	-0.14	0.23	-9999	-0.5	140	140
MAPK8	-0.06	0.12	-9999	-0.35	23	23
HRAS/GTP	-0.11	0.14	-9999	-0.47	25	25
tube development	-0.082	0.13	-9999	-0.39	16	16
MAPK1	-0.078	0.14	-9999	-0.45	25	25
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.056	0.12	-9999	-0.23	139	139
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
PDLIM7	0.01	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.13	0.18	-9999	-0.52	55	55
SHC1	0.01	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.12	0.16	-9999	-0.3	186	186
RET51/GFRalpha1/GDNF/Dok5	-0.16	0.18	-9999	-0.32	237	237
PRKCA	0.008	0.033	-9999	-0.5	2	2
HRAS/GDP	0	0	-9999	-10000	0	0
CREB1	-0.072	0.14	-9999	-0.28	139	139
PIK3R1	0.009	0.024	-9999	-0.5	1	1
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.056	0.12	-9999	-0.23	139	139
RET51/GFRalpha1/GDNF/Grb7	-0.12	0.16	-9999	-0.3	190	190
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.059	0.18	-9999	-0.51	62	62
DOK4	0.01	0	-9999	-10000	0	0
JNK cascade	-0.052	0.12	-9999	-0.34	25	25
RET9/GFRalpha1/GDNF/FRS2	-0.086	0.13	-9999	-0.27	148	148
SHANK3	0.002	0.062	-9999	-0.5	7	7
RASA1	0.01	0	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.056	0.12	-9999	-0.23	139	139
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.071	0.13	-9999	-0.37	24	24
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.07	0.13	-9999	-0.37	24	24
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.073	0.14	-9999	-0.28	82	82
PI3K	-0.089	0.19	-9999	-0.52	28	28
SOS1	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.082	0.13	-9999	-0.5	9	9
GRB10	0.01	0	-9999	-10000	0	0
activation of MAPKK activity	-0.065	0.12	-9999	-0.34	24	24
RET51/GFRalpha1/GDNF/FRS2	-0.12	0.16	-9999	-0.3	188	188
GAB1	0.009	0.024	-9999	-0.5	1	1
IRS1	0.009	0.024	-9999	-0.5	1	1
IRS2	0.009	0.024	-9999	-0.5	1	1
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.073	0.14	-9999	-0.42	25	25
RET51/GFRalpha1/GDNF/PKC alpha	-0.12	0.16	-9999	-0.32	129	129
GRB2	0.01	0	-9999	-10000	0	0
PRKACA	0.01	0	-9999	-10000	0	0
GDNF	-0.004	0.071	-9999	-0.51	9	9
RAC1	0.01	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.12	0.16	-9999	-0.32	128	128
Rac1/GTP	-0.096	0.13	-9999	-0.4	28	28
RET9/GFRalpha1/GDNF	-0.096	0.14	-9999	-0.31	146	146
GFRalpha1/GDNF	-0.11	0.17	-9999	-0.36	146	146

×

BMP receptor signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.077	0.13	-9999	-0.51	17	17
SMAD6-7/SMURF1	-0.043	0.1	-9999	-0.3	68	68
NOG	-0.029	0.14	-9999	-0.5	35	35
SMAD9	-0.12	0.2	-9999	-0.48	102	102
SMAD4	0.01	0	-9999	-10000	0	0
SMAD5	-0.028	0.12	-9999	-0.35	24	24
BMP7/USAG1	-0.27	0.2	-9999	-0.39	328	328
SMAD5/SKI	-0.021	0.11	-9999	-0.4	11	11
SMAD1	0.023	0.029	-9999	-10000	0	0
BMP2	-0.063	0.18	-9999	-0.5	67	67
SMAD1/SMAD1/SMAD4	-0.028	0.068	-9999	-0.41	1	1
BMPR1A	0.01	0	-9999	-10000	0	0
BMPR1B	-0.044	0.16	-9999	-0.5	49	49
BMPR1A-1B/BAMBI	-0.044	0.11	-9999	-0.31	66	66
AHSG	-0.034	0.14	-9999	-0.51	35	35
CER1	-0.005	0.058	-9999	-0.51	6	6
BMP2-4/CER1	-0.054	0.12	-9999	-0.32	79	79
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.02	0.12	-9999	-0.4	21	21
BMP2-4 (homodimer)	-0.06	0.14	-9999	-0.37	75	75
RGMB	0.01	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.066	0.13	-9999	-0.47	20	20
RGMA	0	0.071	-9999	-0.51	9	9
SMURF1	0.01	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.026	0.11	-9999	-0.36	21	21
BMP2-4/USAG1	-0.24	0.19	-9999	-0.35	324	324
SMAD6/SMURF1/SMAD5	-0.021	0.11	-9999	-0.41	10	10
SOSTDC1	-0.33	0.24	-9999	-0.5	307	307
BMP7/BMPR2/BMPR1A-1B	-0.06	0.12	-9999	-0.34	26	26
SKI	0.01	0	-9999	-10000	0	0
BMP6 (homodimer)	-0.068	0.18	-9999	-0.5	71	71
HFE2	-0.007	0.079	-9999	-0.51	11	11
ZFYVE16	0.01	0	-9999	-10000	0	0
MAP3K7	0.01	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.062	0.13	-9999	-0.32	89	89
SMAD5/SMAD5/SMAD4	-0.021	0.11	-9999	-0.41	10	10
MAPK1	0.01	0	-9999	-10000	0	0
TAK1/TAB family	-0.041	0.081	-9999	-0.36	12	12
BMP7 (homodimer)	-0.055	0.17	-9999	-0.5	59	59
NUP214	0.01	0	-9999	-10000	0	0
BMP6/FETUA	-0.081	0.16	-9999	-0.37	102	102
SMAD1/SKI	0.027	0.027	-9999	-10000	0	0
SMAD6	-0.064	0.18	-9999	-0.5	68	68
CTDSP2	0.01	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.073	0.14	-9999	-0.32	105	105
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.35	0.24	-9999	-0.51	324	324
BMPR2 (homodimer)	0.01	0	-9999	-10000	0	0
GADD34/PP1CA	-0.001	0.019	-9999	-0.29	2	2
BMPR1A-1B (homodimer)	-0.037	0.11	-9999	-0.35	49	49
CHRDL1	-0.17	0.24	-9999	-0.5	166	166
ENDOFIN/SMAD1	0.027	0.027	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.033	0.077	-9999	-0.46	1	1
SMAD6/SMURF1	0.01	0	-9999	-10000	0	0
BAMBI	-0.013	0.11	-9999	-0.51	21	21
SMURF2	0.01	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.15	0.2	-9999	-0.37	192	192
BMP2-4/GREM1	-0.26	0.18	-9999	-0.35	345	345
SMAD7	0.009	0.024	-9999	-0.5	1	1
SMAD8A/SMAD8A/SMAD4	-0.091	0.2	-9999	-0.45	102	102
SMAD1/SMAD6	0.027	0.027	-9999	-10000	0	0
TAK1/SMAD6	0	0	-9999	-10000	0	0
BMP7	-0.055	0.17	-9999	-0.5	59	59
BMP6	-0.068	0.18	-9999	-0.5	71	71
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.02	0.11	-9999	-0.38	15	15
PPM1A	0.01	0	-9999	-10000	0	0
SMAD1/SMURF2	0.027	0.027	-9999	-10000	0	0
SMAD7/SMURF1	-0.001	0.016	-9999	-0.35	1	1
CTDSPL	0.01	0	-9999	-10000	0	0
PPP1CA	0.01	0	-9999	-10000	0	0
XIAP	0.01	0	-9999	-10000	0	0
CTDSP1	0.01	0	-9999	-10000	0	0
PPP1R15A	0.008	0.033	-9999	-0.5	2	2
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.04	0.13	-9999	-0.38	34	34
CHRD	-0.011	0.1	-9999	-0.51	19	19
BMPR2	0.01	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.032	0.12	-9999	-0.4	21	21
BMP4	-0.004	0.084	-9999	-0.5	13	13
FST	-0.036	0.15	-9999	-0.51	41	41
BMP2-4/NOG	-0.071	0.15	-9999	-0.34	97	97
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.055	0.11	-9999	-0.49	7	7

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.023	0.094	-9999	-0.42	22	22
alphaM/beta2 Integrin/GPIbA	-0.028	0.1	-9999	-0.4	29	29
alphaM/beta2 Integrin/proMMP-9	-0.082	0.15	-9999	-0.33	113	113
PLAUR	0.01	0	-9999	-10000	0	0
HMGB1	0.006	0.011	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.023	0.097	-9999	-0.44	21	21
AGER	-0.47	0.15	-9999	-0.51	428	428
RAP1A	0.01	0	-9999	-10000	0	0
SELPLG	-0.008	0.093	-9999	-0.5	16	16
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.29	0.16	-9999	-0.51	120	120
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.094	0.21	-9999	-0.51	93	93
CYR61	-0.019	0.12	-9999	-0.5	26	26
TLN1	0.009	0.024	-9999	-0.5	1	1
Rap1/GTP	-0.084	0.14	-9999	-0.43	45	45
RHOA	0.01	0	-9999	-10000	0	0
P-selectin oligomer	-0.1	0.21	-9999	-0.5	104	104
MYH2	-0.15	0.2	-9999	-0.47	96	96
MST1R	0.008	0.033	-9999	-0.5	2	2
leukocyte activation during inflammatory response	-0.045	0.11	-9999	-0.31	62	62
APOB	-0.042	0.15	-9999	-0.51	46	46
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	0.009	0.024	-9999	-0.51	1	1
JAM3	0.004	0.052	-9999	-0.5	5	5
GP1BA	0	0.07	-9999	-0.5	9	9
alphaM/beta2 Integrin/CTGF	-0.039	0.13	-9999	-0.4	42	42
alphaM/beta2 Integrin	-0.088	0.18	-9999	-0.44	61	61
JAM3 homodimer	0.004	0.052	-9999	-0.5	5	5
ICAM2	0.004	0.052	-9999	-0.5	5	5
ICAM1	0.002	0.062	-9999	-0.5	7	7
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.087	0.18	-9999	-0.44	61	61
cell adhesion	-0.028	0.1	-9999	-0.4	29	29
NFKB1	-0.3	0.22	-9999	-0.62	120	120
THY1	-0.006	0.089	-9999	-0.51	14	14
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.032	0.095	-9999	-0.31	49	49
alphaM/beta2 Integrin/LRP/tPA	-0.053	0.14	-9999	-0.42	33	33
IL6	-0.35	0.33	-9999	-0.85	126	126
ITGB2	-0.006	0.075	-9999	-0.51	10	10
elevation of cytosolic calcium ion concentration	-0.068	0.13	-9999	-0.38	28	28
alphaM/beta2 Integrin/JAM2/JAM3	-0.049	0.14	-9999	-0.37	62	62
JAM2	-0.046	0.16	-9999	-0.5	51	51
alphaM/beta2 Integrin/ICAM1	-0.028	0.11	-9999	-0.55	13	13
alphaM/beta2 Integrin/uPA/Plg	-0.076	0.14	-9999	-0.32	88	88
RhoA/GTP	-0.1	0.19	-9999	-0.49	60	60
positive regulation of phagocytosis	-0.079	0.16	-9999	-0.66	26	26
Ron/MSP	-0.013	0.068	-9999	-0.36	17	17
alphaM/beta2 Integrin/uPAR/uPA	-0.068	0.13	-9999	-0.38	28	28
alphaM/beta2 Integrin/uPAR	-0.022	0.093	-9999	-0.43	21	21
PLAU	-0.089	0.2	-9999	-0.51	88	88
PLAT	-0.054	0.17	-9999	-0.51	57	57
actin filament polymerization	-0.15	0.2	-9999	-0.45	96	96
MST1	-0.007	0.092	-9999	-0.51	15	15
alphaM/beta2 Integrin/lipoprotein(a)	-0.045	0.12	-9999	-0.31	62	62
TNF	-0.28	0.23	-9999	-0.61	120	120
RAP1B	0.01	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.079	0.14	-9999	-0.33	108	108
fibrinolysis	-0.076	0.14	-9999	-0.31	88	88
HCK	-0.011	0.1	-9999	-0.5	19	19
dendritic cell antigen processing and presentation	-0.087	0.18	-9999	-0.44	61	61
VTN	-0.084	0.2	-9999	-0.5	86	86
alphaM/beta2 Integrin/CYR61	-0.039	0.12	-9999	-0.39	43	43
LPA	0	0.041	-9999	-0.51	3	3
LRP1	0.005	0.047	-9999	-0.5	4	4
cell migration	-0.072	0.13	-9999	-0.3	106	106
FN1	0.005	0.047	-9999	-0.5	4	4
alphaM/beta2 Integrin/Thy1	-0.031	0.1	-9999	-0.38	35	35
MPO	-0.002	0.077	-9999	-0.5	11	11
KNG1	-0.03	0.13	-9999	-0.51	31	31
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.093	0.18	-9999	-0.46	57	57
ELA2	0	0	-9999	-10000	0	0
PLG	-0.008	0.071	-9999	-0.51	9	9
CTGF	-0.02	0.12	-9999	-0.5	27	27
alphaM/beta2 Integrin/Hck	-0.033	0.14	-9999	-0.55	26	26
ITGAM	-0.017	0.1	-9999	-0.51	20	20
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.084	0.18	-9999	-0.35	111	111
HP	-0.14	0.23	-9999	-0.5	134	134
leukocyte adhesion	-0.27	0.19	-9999	-0.48	157	157
SELP	-0.1	0.21	-9999	-0.5	104	104

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.009	0.024	-9999	-0.51	1	1
LAT2	-0.091	0.2	-9999	-0.48	74	74
AP1	-0.13	0.21	-9999	-0.5	93	93
mol:PIP3	-0.096	0.22	-9999	-0.51	82	82
IKBKB	-0.042	0.13	-9999	-0.27	77	77
AKT1	-0.063	0.16	-9999	-0.38	71	71
IKBKG	-0.042	0.13	-9999	-0.27	77	77
MS4A2	-0.11	0.22	-9999	-0.5	109	109
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.009	0.002	-9999	-10000	0	0
MAP3K1	-0.064	0.18	-9999	-0.4	82	82
mol:Ca2+	-0.068	0.17	-9999	-0.37	82	82
LYN	0.008	0.005	-9999	-10000	0	0
CBLB	-0.086	0.19	-9999	-0.45	73	73
SHC1	0.01	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.027	0.079	-9999	-0.26	47	47
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0.007	0.041	-9999	-0.5	3	3
PLD2	-0.095	0.19	-9999	-0.47	70	70
PTPN13	-0.11	0.22	-9999	-0.5	90	90
PTPN11	0.007	0.008	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.043	0.15	-9999	-0.32	72	72
SYK	0.005	0.043	-9999	-0.53	3	3
GRB2	0.009	0.001	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.14	0.2	-9999	-0.52	83	83
LAT	-0.086	0.19	-9999	-0.45	73	73
PAK2	-0.079	0.2	-9999	-0.46	82	82
NFATC2	-0.071	0.16	-9999	-0.74	20	20
HRAS	-0.093	0.23	-9999	-0.51	82	82
GAB2	0.005	0.047	-9999	-0.5	4	4
PLA2G1B	-0.002	0.031	-9999	-10000	0	0
Fc epsilon R1	-0.15	0.22	-9999	-0.41	171	171
Antigen/IgE/Fc epsilon R1	-0.14	0.2	-9999	-0.37	171	171
mol:GDP	-0.11	0.24	-9999	-0.55	84	84
JUN	0.005	0.047	-9999	-0.5	4	4
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.008	0.024	-9999	-0.5	1	1
FOS	-0.024	0.13	-9999	-0.5	31	31
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.12	0.18	-9999	-0.39	114	114
CHUK	-0.042	0.13	-9999	-0.27	77	77
KLRG1	-0.082	0.18	-9999	-0.43	72	72
VAV1	-0.089	0.2	-9999	-0.46	74	74
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.086	0.19	-9999	-0.45	74	74
negative regulation of mast cell degranulation	-0.072	0.17	-9999	-0.4	72	72
BTK	-0.12	0.27	-9999	-0.59	85	85
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.11	0.22	-9999	-0.58	70	70
GAB2/PI3K/SHP2	-0.1	0.16	-9999	-0.42	72	72
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.097	0.2	-9999	-0.5	71	71
RAF1	0.021	0.023	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.12	0.19	-9999	-0.5	70	70
FCER1G	-0.002	0.087	-9999	-0.51	13	13
FCER1A	-0.13	0.23	-9999	-0.51	124	124
Antigen/IgE/Fc epsilon R1/Fyn	-0.12	0.18	-9999	-0.5	71	71
MAPK3	0.028	0.02	-9999	-10000	0	0
MAPK1	0.028	0.02	-9999	-10000	0	0
NFKB1	0.01	0	-9999	-10000	0	0
MAPK8	-0.011	0.061	-9999	-10000	0	0
DUSP1	-0.041	0.15	-9999	-0.5	47	47
NF-kappa-B/RelA	-0.043	0.062	-9999	-0.23	7	7
actin cytoskeleton reorganization	-0.094	0.2	-9999	-0.48	72	72
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.11	0.18	-9999	-0.45	80	80
FER	-0.086	0.19	-9999	-0.45	72	72
RELA	0.01	0	-9999	-10000	0	0
ITK	-0.038	0.089	-9999	-0.53	12	12
SOS1	0.01	0	-9999	-10000	0	0
PLCG1	-0.1	0.24	-9999	-0.55	82	82
cytokine secretion	-0.031	0.045	-9999	-10000	0	0
SPHK1	-0.088	0.19	-9999	-0.45	75	75
PTK2	-0.098	0.21	-9999	-0.51	72	72
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.14	0.22	-9999	-0.54	83	83
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.092	0.22	-9999	-0.49	83	83
MAP2K2	0.025	0.02	-9999	-10000	0	0
MAP2K1	0.025	0.02	-9999	-10000	0	0
MAP2K7	0.01	0	-9999	-10000	0	0
KLRG1/SHP2	-0.092	0.15	-9999	-0.38	72	72
MAP2K4	0.011	0.011	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.13	0.2	-9999	-0.52	72	72
mol:Choline	-0.094	0.18	-9999	-0.46	70	70
SHC/Grb2/SOS1	-0.099	0.16	-9999	-0.42	71	71
FYN	0.009	0.024	-9999	-0.5	1	1
DOK1	0.01	0	-9999	-10000	0	0
PXN	-0.085	0.19	-9999	-0.46	71	71
HCLS1	-0.088	0.19	-9999	-0.46	74	74
PRKCB	-0.069	0.17	-9999	-0.38	83	83
FCGR2B	0.009	0.024	-9999	-0.5	1	1
IGHE	-0.002	0.006	-9999	-10000	0	0
KLRG1/SHIP	-0.074	0.17	-9999	-0.41	72	72
LCP2	0.006	0.041	-9999	-0.5	3	3
PLA2G4A	-0.12	0.22	-9999	-0.48	92	92
RASA1	0.01	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.094	0.18	-9999	-0.46	70	70
IKK complex	-0.019	0.099	-9999	-0.24	23	23
WIPF1	0.01	0	-9999	-10000	0	0

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.18	0.14	-9999	-0.52	21	21
NF kappa B1 p50/RelA/I kappa B alpha	-0.16	0.11	-9999	-0.46	21	21
alphaV/beta3 Integrin/Osteopontin/Src	-0.26	0.16	-9999	-0.36	339	339
AP1	-0.17	0.13	-9999	-0.45	46	46
ILK	-0.19	0.15	-9999	-0.54	21	21
bone resorption	-0.16	0.11	-9999	-0.44	27	27
PTK2B	0.008	0.033	-9999	-0.5	2	2
PYK2/p130Cas	-0.18	0.12	-9999	-0.49	24	24
ITGAV	0.011	0.003	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.007	0.049	-9999	-0.35	9	9
alphaV/beta3 Integrin/Osteopontin	-0.23	0.15	-9999	-0.38	105	105
MAP3K1	-0.19	0.15	-9999	-0.36	85	85
JUN	0.006	0.047	-9999	-0.5	4	4
MAPK3	-0.18	0.15	-9999	-0.38	84	84
MAPK1	-0.18	0.15	-9999	-0.38	84	84
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0.01	0	-9999	-10000	0	0
MAPK8	-0.17	0.14	-9999	-0.51	21	21
ITGB3	-0.019	0.12	-9999	-0.51	27	27
NFKBIA	-0.16	0.15	-9999	-0.37	80	80
FOS	-0.024	0.13	-9999	-0.5	31	31
CD44	0.001	0.066	-9999	-0.5	8	8
CHUK	0.01	0	-9999	-10000	0	0
PLAU	-0.18	0.18	-9999	-0.51	74	74
NF kappa B1 p50/RelA	-0.16	0.12	-9999	-0.48	21	21
BCAR1	0.009	0.024	-9999	-0.5	1	1
RELA	0.01	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.021	0.084	-9999	-0.36	27	27
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.2	0.15	-9999	-0.54	21	21
VAV3	-0.18	0.14	-9999	-0.51	25	25
MAP3K14	-0.2	0.15	-9999	-0.38	84	84
ROCK2	0.009	0.024	-9999	-0.5	1	1
SPP1	-0.37	0.23	-9999	-0.51	339	339
RAC1	0.01	0	-9999	-10000	0	0
Rac1/GTP	-0.17	0.12	-9999	-0.47	25	25
MMP2	-0.13	0.13	-9999	-0.43	18	18

×

TCGA08_retinoblastoma

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
CDKN2B	-0.023	0.12	-10000	0	-0.47	33	33
CDKN2C	0.022	0.032	-10000	0	-0.45	1	1
CDKN2A	-0.16	0.25	-10000	0	-0.53	142	142
CCND2	0.042	0.066	0.2	34	-0.12	5	39
RB1	-0.046	0.068	-10000	0	-0.2	35	35
CDK4	0.05	0.071	0.21	35	-10000	0	35
CDK6	0.047	0.071	0.22	34	-10000	0	34
G1/S progression	0.038	0.074	0.2	35	-10000	0	35

×

TCGA08_p53

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
CDKN2A	-0.11	0.18	-10000	0	-0.37	142	142
TP53	-0.028	0.045	0.18	1	-10000	0	1
Senescence	-0.028	0.045	0.18	1	-10000	0	1
Apoptosis	-0.028	0.045	0.18	1	-10000	0	1
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.054	0.089	0.18	141	-0.33	2	143
MDM4	0.01	0	-10000	0	-10000	0	0

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.21	0.31	-10000	0	-0.86	42	42
PCK1	-0.17	0.23	-10000	0	-0.68	34	34
HNF4A	-0.39	0.5	-10000	0	-1	122	122
KCNJ11	-0.18	0.33	-10000	0	-0.91	43	43
AKT1	-0.072	0.14	-10000	0	-0.42	6	6
response to starvation	-0.028	0.047	-10000	0	-10000	0	0
DLK1	-0.2	0.32	-10000	0	-0.9	40	40
NKX2-1	-0.12	0.38	-10000	0	-1.3	35	35
ACADM	-0.21	0.31	-10000	0	-0.88	39	39
TAT	-0.16	0.22	-10000	0	-0.73	21	21
CEBPB	0.009	0.005	-10000	0	-10000	0	0
CEBPA	-0.017	0.11	-10000	0	-0.5	24	24
TTR	-0.19	0.25	-10000	0	-0.74	44	44
PKLR	-0.22	0.32	-10000	0	-0.86	47	47
APOA1	-0.49	0.63	-10000	0	-1.3	157	157
CPT1C	-0.22	0.32	-10000	0	-0.91	40	40
ALAS1	-0.073	0.16	-10000	0	-10000	0	0
TFRC	-0.16	0.26	-10000	0	-0.84	20	20
FOXF1	-0.083	0.2	0.22	2	-0.48	88	90
NF1	0.016	0	-10000	0	-10000	0	0
HNF1A (dimer)	-0.11	0.23	-10000	0	-0.57	92	92
CPT1A	-0.21	0.31	-10000	0	-0.88	39	39
HMGCS1	-0.21	0.31	-10000	0	-0.86	42	42
NR3C1	0.004	0.033	-10000	0	-10000	0	0
CPT1B	-0.21	0.32	-10000	0	-0.84	50	50
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	-0.001	0.026	-10000	0	-10000	0	0
GCK	-0.22	0.34	-10000	0	-0.89	52	52
CREB1	0.006	0.02	-10000	0	-10000	0	0
IGFBP1	-0.13	0.2	-10000	0	-0.61	19	19
PDX1	-0.16	0.26	-10000	0	-0.66	61	61
UCP2	-0.21	0.31	-10000	0	-0.86	42	42
ALDOB	-0.2	0.34	-10000	0	-0.88	50	50
AFP	-0.07	0.14	-10000	0	-0.51	17	17
BDH1	-0.21	0.32	-10000	0	-0.88	40	40
HADH	-0.17	0.31	-10000	0	-0.86	37	37
F2	-0.32	0.43	-10000	0	-1.1	62	62
HNF1A	-0.11	0.23	-10000	0	-0.58	92	92
G6PC	-0.079	0.16	-10000	0	-0.59	14	14
SLC2A2	-0.15	0.23	-10000	0	-0.67	28	28
INS	0.001	0.028	-10000	0	-10000	0	0
FOXA1	-0.014	0.11	0.25	6	-0.54	13	19
FOXA3	-0.16	0.27	-10000	0	-0.57	130	130
FOXA2	-0.21	0.36	-10000	0	-0.94	46	46
ABCC8	-0.24	0.39	-10000	0	-0.95	76	76
ALB	-0.081	0.16	-10000	0	-0.46	35	35

×

Visual signal transduction: Rods

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.01	0	-9999	-10000	0	0
GNAT1/GTP	-0.007	0.051	-9999	-0.37	9	9
Metarhodopsin II/Arrestin	-0.001	0.015	-9999	-0.32	1	1
PDE6G/GNAT1/GTP	-0.01	0.06	-9999	-0.35	13	13
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	-0.008	0.071	-9999	-0.51	9	9
GRK1	-0.026	0.12	-9999	-0.51	28	28
CNG Channel	-0.1	0.15	-9999	-0.49	37	37
mol:Na +	-0.12	0.15	-9999	-0.49	38	38
mol:ADP	-0.026	0.12	-9999	-0.51	28	28
RGS9-1/Gbeta5/R9AP	-0.14	0.17	-9999	-0.33	195	195
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.12	0.16	-9999	-0.5	38	38
CNGB1	-0.085	0.2	-9999	-0.51	85	85
RDH5	-0.001	0.076	-9999	-0.51	10	10
SAG	0.001	0.024	-9999	-0.51	1	1
mol:Ca2+	-0.093	0.16	-9999	-0.47	38	38
Na + (4 Units)	-0.11	0.14	-9999	-0.46	38	38
RGS9	-0.15	0.24	-9999	-0.5	149	149
GNB1/GNGT1	-0.071	0.14	-9999	-0.36	91	91
GNAT1/GDP	-0.12	0.15	-9999	-0.29	157	157
GUCY2D	0.001	0.067	-9999	-0.51	8	8
GNGT1	-0.095	0.21	-9999	-0.51	91	91
GUCY2F	0.001	0.024	-9999	-0.51	1	1
GNB5	0.01	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.014	0.096	-9999	-0.27	56	56
mol:11-cis-retinal	-0.001	0.076	-9999	-0.51	10	10
mol:cGMP	-0.052	0.11	-9999	-0.51	4	4
GNB1	0.01	0	-9999	-10000	0	0
Rhodopsin	-0.008	0.053	-9999	-0.37	10	10
SLC24A1	0.01	0	-9999	-10000	0	0
CNGA1	-0.064	0.18	-9999	-0.51	66	66
Metarhodopsin II	-0.017	0.067	-9999	-0.28	28	28
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.055	0.12	-9999	-0.28	91	91
RGS9BP	-0.067	0.18	-9999	-0.5	70	70
Metarhodopsin II/Transducin	-0.02	0.061	-9999	-0.22	3	3
GCAP Family/Ca ++	-0.052	0.11	-9999	-0.29	83	83
PDE6A/B	-0.034	0.1	-9999	-0.35	45	45
mol:Pi	-0.14	0.17	-9999	-0.32	195	195
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.059	0.12	-9999	-0.29	97	97
PDE6B	0.002	0.062	-9999	-0.5	7	7
PDE6A	-0.032	0.14	-9999	-0.5	38	38
PDE6G	0.003	0.058	-9999	-0.5	6	6
RHO	0.004	0.005	-9999	-10000	0	0
PDE6	-0.13	0.16	-9999	-0.48	53	53
GUCA1A	-0.08	0.2	-9999	-0.51	79	79
GC2/GCAP Family	-0.052	0.11	-9999	-0.29	84	84
GUCA1C	0	0.001	-9999	-10000	0	0
GUCA1B	0.001	0.067	-9999	-0.51	8	8

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.002	0.024	-9999	-0.3	3	3
ARNO/beta Arrestin1-2	-0.094	0.11	-9999	-0.36	13	13
EGFR	-0.006	0.088	-9999	-0.51	14	14
EPHA2	0	0.07	-9999	-0.5	9	9
USP6	0.01	0	-9999	-10000	0	0
IQSEC1	0.009	0.024	-9999	-0.5	1	1
EGFR/EGFR/EGF/EGF	-0.08	0.16	-9999	-0.37	101	101
ARRB2	-0.007	0.056	-9999	-0.19	41	41
mol:GTP	0.011	0.022	-9999	-0.13	2	2
ARRB1	0.005	0.047	-9999	-0.5	4	4
FBXO8	0.01	0	-9999	-10000	0	0
TSHR	-0.042	0.16	-9999	-0.51	46	46
EGF	-0.091	0.21	-9999	-0.51	90	90
somatostatin receptor activity	0	0	-9999	-0.001	111	111
ARAP2	-0.009	0.096	-9999	-0.5	17	17
mol:GDP	-0.086	0.12	-9999	-0.26	112	112
mol:PI-3-4-5-P3	0	0	-9999	-0.001	55	55
ITGA2B	-0.042	0.15	-9999	-0.5	47	47
ARF6	0.01	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.006	0.037	-9999	-0.26	10	10
ADAP1	0.009	0.024	-9999	-0.5	1	1
KIF13B	0.008	0.033	-9999	-0.5	2	2
HGF/MET	-0.042	0.12	-9999	-0.38	52	52
PXN	0.01	0	-9999	-10000	0	0
ARF6/GTP	-0.081	0.11	-9999	-0.24	108	108
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.067	0.13	-9999	-0.31	101	101
ADRB2	-0.19	0.25	-9999	-0.5	181	181
receptor agonist activity	0	0	-9999	0	116	116
actin filament binding	0	0	-9999	0	118	118
SRC	0.01	0	-9999	-10000	0	0
ITGB3	-0.02	0.12	-9999	-0.51	27	27
GNAQ	0.009	0.024	-9999	-0.5	1	1
EFA6/PI-4-5-P2	0	0	-9999	-0.001	79	79
ARF6/GDP	-0.01	0.075	-9999	-0.37	8	8
ARF6/GDP/GULP/ACAP1	-0.078	0.095	-9999	-0.29	39	39
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.041	0.097	-9999	-0.26	73	73
ACAP1	0.008	0.033	-9999	-0.5	2	2
ACAP2	0.009	0.024	-9999	-0.51	1	1
LHCGR/beta Arrestin2	-0.022	0.078	-9999	-0.27	41	41
EFNA1	0.009	0.024	-9999	-0.5	1	1
HGF	-0.019	0.12	-9999	-0.5	26	26
CYTH3	0.007	0.025	-9999	-0.37	2	2
CYTH2	0.006	0.002	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	0	75	75
endosomal lumen acidification	0	0	-9999	0	31	31
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	0.009	0.024	-9999	-0.5	1	1
GNAQ/ARNO	0.007	0.014	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	35	35
MET	-0.022	0.12	-9999	-0.51	29	29
GNA14	-0.006	0.087	-9999	-0.5	14	14
GNA15	0.01	0	-9999	-10000	0	0
GIT1	0.01	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	94	94
GNA11	0.007	0.033	-9999	-0.5	2	2
LHCGR	-0.04	0.15	-9999	-0.51	41	41
AGTR1	-0.15	0.24	-9999	-0.5	145	145
desensitization of G-protein coupled receptor protein signaling pathway	-0.021	0.078	-9999	-0.27	41	41
IPCEF1/ARNO	-0.045	0.1	-9999	-0.46	3	3
alphaIIb/beta3 Integrin	-0.056	0.13	-9999	-0.36	73	73

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.03	0.085	0.32	6	-10000	0	6
SMARCC2	0.011	0.005	-10000	0	-10000	0	0
SMARCC1	0.011	0.005	-10000	0	-10000	0	0
TBX21	-0.11	0.22	-10000	0	-0.57	56	56
SUMO2	0.009	0.005	-10000	0	-10000	0	0
STAT1 (dimer)	0.017	0	-10000	0	-10000	0	0
FKBP4	0.009	0.024	-10000	0	-0.51	1	1
FKBP5	0.007	0.041	-10000	0	-0.5	3	3
GR alpha/HSP90/FKBP51/HSP90	0.09	0.11	0.28	59	-10000	0	59
PRL	-0.069	0.13	-10000	0	-0.6	4	4
cortisol/GR alpha (dimer)/TIF2	0.21	0.26	0.54	131	-10000	0	131
RELA	-0.033	0.09	-10000	0	-0.27	7	7
FGG	0.002	0.33	0.49	51	-0.46	110	161
GR beta/TIF2	0.094	0.12	0.31	61	-0.26	1	62
IFNG	-0.23	0.28	-10000	0	-0.77	60	60
apoptosis	-0.014	0.15	0.48	9	-0.56	13	22
CREB1	-0.005	0.048	-10000	0	-10000	0	0
histone acetylation	-0.031	0.14	0.26	6	-0.37	32	38
BGLAP	-0.064	0.14	-10000	0	-0.52	6	6
GR/PKAc	0.088	0.1	0.28	56	-10000	0	56
NF kappa B1 p50/RelA	-0.058	0.16	-10000	0	-0.44	28	28
SMARCD1	0.011	0.005	-10000	0	-10000	0	0
MDM2	0.076	0.097	0.25	66	-0.23	1	67
GATA3	0.012	0.042	-10000	0	-0.5	3	3
AKT1	0	0	-10000	0	-10000	0	0
CSF2	-0.12	0.31	-10000	0	-1	39	39
GSK3B	0.009	0.005	-10000	0	-10000	0	0
NR1I3	0.01	0.14	0.47	7	-0.56	4	11
CSN2	0.12	0.17	0.4	52	-10000	0	52
BRG1/BAF155/BAF170/BAF60A	0.02	0.025	-10000	0	-0.32	1	1
NFATC1	0.007	0.047	-10000	0	-0.5	4	4
POU2F1	0.01	0.015	-10000	0	-10000	0	0
CDKN1A	0.025	0.062	-10000	0	-1.3	1	1
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0	0.005	-10000	0	-10000	0	0
SFN	0	0.072	-10000	0	-0.51	9	9
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.085	0.11	0.28	54	-10000	0	54
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.022	0.23	0.45	7	-0.81	30	37
JUN	-0.17	0.18	-10000	0	-0.5	67	67
IL4	-0.079	0.15	-10000	0	-0.61	12	12
CDK5R1	-0.006	0.089	-10000	0	-0.52	14	14
PRKACA	0.01	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.13	0.22	0.21	1	-0.48	83	84
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.091	0.1	0.28	56	-10000	0	56
cortisol/GR alpha (monomer)	0.25	0.32	0.65	132	-10000	0	132
NCOA2	0.005	0.047	-10000	0	-0.5	4	4
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.075	0.14	-10000	0	-0.57	31	31
AP-1/NFAT1-c-4	-0.28	0.28	-10000	0	-0.66	125	125
AFP	-0.14	0.17	-10000	0	-0.65	14	14
SUV420H1	0.01	0	-10000	0	-10000	0	0
IRF1	0.13	0.15	0.42	47	-10000	0	47
TP53	0.026	0.024	-10000	0	-0.48	1	1
PPP5C	0.01	0	-10000	0	-10000	0	0
KRT17	-0.27	0.34	-10000	0	-0.89	74	74
KRT14	-0.18	0.2	-10000	0	-0.51	68	68
TBP	0.017	0	-10000	0	-10000	0	0
CREBBP	0.052	0.062	-10000	0	-10000	0	0
HDAC1	0.008	0.004	-10000	0	-10000	0	0
HDAC2	0.015	0.023	-10000	0	-10000	0	0
AP-1	-0.28	0.29	-10000	0	-0.67	125	125
MAPK14	0.009	0.005	-10000	0	-10000	0	0
MAPK10	-0.047	0.16	-10000	0	-0.5	52	52
MAPK11	0.006	0.041	-10000	0	-0.5	3	3
KRT5	-0.4	0.5	-10000	0	-1.1	142	142
interleukin-1 receptor activity	0.005	0.023	-10000	0	-10000	0	0
NCOA1	0.012	0.001	-10000	0	-10000	0	0
STAT1	0.017	0	-10000	0	-10000	0	0
CGA	-0.11	0.19	-10000	0	-0.57	36	36
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.12	0.18	0.49	60	-10000	0	60
MAPK3	0.009	0.005	-10000	0	-10000	0	0
MAPK1	0.009	0.005	-10000	0	-10000	0	0
ICAM1	-0.14	0.24	-10000	0	-0.6	61	61
NFKB1	-0.033	0.09	-10000	0	-0.26	15	15
MAPK8	-0.15	0.17	-10000	0	-0.45	72	72
MAPK9	0.009	0.005	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.018	0.16	0.48	9	-0.59	13	22
BAX	0.027	0.021	-10000	0	-10000	0	0
POMC	-0.19	0.32	-10000	0	-0.97	40	40
EP300	0.052	0.062	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/p53	0.23	0.26	0.56	130	-10000	0	130
proteasomal ubiquitin-dependent protein catabolic process	0.053	0.075	0.22	25	-0.2	1	26
SGK1	0.096	0.093	-10000	0	-1.1	1	1
IL13	-0.16	0.2	-10000	0	-0.61	34	34
IL6	-0.3	0.45	-10000	0	-1	117	117
PRKACG	0.002	0.004	-10000	0	-10000	0	0
IL5	-0.14	0.17	-10000	0	-0.54	28	28
IL2	-0.21	0.24	-10000	0	-0.67	52	52
CDK5	0.009	0.003	-10000	0	-10000	0	0
PRKACB	0.009	0.024	-10000	0	-0.51	1	1
HSP90AA1	0.01	0	-10000	0	-10000	0	0
IL8	-0.14	0.23	-10000	0	-0.67	42	42
CDK5R1/CDK5	-0.01	0.063	-10000	0	-0.37	14	14
NF kappa B1 p50/RelA/PKAc	-0.025	0.12	-10000	0	-0.38	14	14
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.21	0.24	0.52	128	-10000	0	128
SMARCA4	0.01	0.024	-10000	0	-0.5	1	1
chromatin remodeling	0.14	0.15	0.38	76	-10000	0	76
NF kappa B1 p50/RelA/Cbp	0.01	0.15	0.36	6	-0.41	9	15
JUN (dimer)	-0.17	0.18	-10000	0	-0.49	67	67
YWHAH	0.01	0	-10000	0	-10000	0	0
VIPR1	-0.36	0.43	-10000	0	-0.86	195	195
NR3C1	0.14	0.19	0.44	86	-10000	0	86
NR4A1	-0.1	0.22	-10000	0	-0.5	107	107
TIF2/SUV420H1	-0.003	0.033	-10000	0	-0.35	4	4
MAPKKK cascade	-0.014	0.15	0.48	9	-0.56	13	22
cortisol/GR alpha (dimer)/Src-1	0.22	0.26	0.55	132	-10000	0	132
PBX1	-0.006	0.088	-10000	0	-0.5	14	14
POU1F1	0.001	0.033	-10000	0	-0.62	1	1
SELE	-0.25	0.43	-10000	0	-1	96	96
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.14	0.15	0.38	76	-10000	0	76
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.21	0.24	0.52	128	-10000	0	128
mol:cortisol	0.13	0.19	0.39	119	-0.21	12	131
MMP1	-0.27	0.19	-10000	0	-0.47	137	137

×

LPA4-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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.002	0.076	-9999	-0.31	26	26
ADCY5	-0.03	0.11	-9999	-0.31	66	66
ADCY6	0.012	0.035	-9999	-0.3	6	6
ADCY7	0.011	0.038	-9999	-0.3	7	7
ADCY1	0.006	0.056	-9999	-0.3	15	15
ADCY2	-0.02	0.1	-9999	-0.31	51	51
ADCY3	0.012	0.032	-9999	-0.3	5	5
ADCY8	-0.12	0.15	-9999	-0.3	194	194
PRKCE	0.005	0.038	-9999	-0.36	5	5
ADCY9	0.006	0.055	-9999	-0.3	15	15
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.062	0.099	-9999	-0.35	26	26

×

Canonical Wnt signaling pathway

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
HDAC1	0.004	0.019	-10000	0	-10000	0	0
AES	0.003	0.016	-10000	0	-10000	0	0
FBXW11	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0	0	-10000	0	-10000	0	0
SMAD4	0.01	0	-10000	0	-10000	0	0
DKK2	-0.092	0.2	-10000	0	-0.5	93	93
TLE1	0.003	0.016	-10000	0	-10000	0	0
MACF1	0.006	0.047	-10000	0	-0.5	4	4
CTNNB1	0.09	0.078	0.24	18	-10000	0	18
WIF1	-0.34	0.23	-10000	0	-0.5	325	325
beta catenin/RanBP3	0.012	0.086	0.39	21	-10000	0	21
KREMEN2	-0.12	0.23	-10000	0	-0.51	119	119
DKK1	-0.13	0.23	-10000	0	-0.51	123	123
beta catenin/beta TrCP1	0.091	0.073	0.23	16	-10000	0	16
FZD1	0.01	0.001	-10000	0	-10000	0	0
AXIN2	-0.025	0.24	-10000	0	-1.3	16	16
AXIN1	0.011	0.001	-10000	0	-10000	0	0
RAN	0.009	0.024	-10000	0	-0.51	1	1
Axin1/APC/GSK3/beta catenin	0.005	0.021	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.074	0.06	0.27	1	-10000	0	1
Axin1/APC/GSK3	0.022	0.062	0.2	43	-10000	0	43
Axin1/APC/GSK3/beta catenin/Macf1	0.067	0.043	-10000	0	-10000	0	0
HNF1A	-0.098	0.21	-10000	0	-0.52	92	92
CTBP1	0.004	0.017	-10000	0	-10000	0	0
MYC	0.006	0.1	-10000	0	-1.4	2	2
RANBP3	0.01	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.13	0.19	-10000	0	-0.36	175	175
NKD1	-0.054	0.17	-10000	0	-0.5	58	58
TCF4	0.001	0.037	-10000	0	-0.5	2	2
TCF3	0.004	0.017	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	-0.004	0.034	-10000	0	-0.26	7	7
Ran/GTP	0	0.017	-10000	0	-0.37	1	1
CtBP/CBP/TCF/TLE1/AES	0.002	0.11	0.44	22	-10000	0	22
LEF1	0.001	0.038	-10000	0	-0.52	2	2
DVL1	0.074	0.053	0.19	1	-0.27	1	2
CSNK2A1	0.01	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.077	0.067	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.15	0.19	-10000	0	-0.35	205	205
LRP6	0.011	0.001	-10000	0	-10000	0	0
CSNK1A1	0.004	0.019	-10000	0	-10000	0	0
NLK	0.01	0.002	-10000	0	-10000	0	0
CCND1	-0.003	0.16	-10000	0	-1.3	6	6
WNT1	0.001	0.068	-10000	0	-0.51	8	8
GSK3A	0.011	0.001	-10000	0	-10000	0	0
GSK3B	0.01	0.001	-10000	0	-10000	0	0
FRAT1	0.009	0.002	-10000	0	-10000	0	0
PPP2R5D	0.074	0.088	0.3	58	-10000	0	58
APC	0.026	0.036	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.15	0.099	0.22	319	-10000	0	319
CREBBP	0.004	0.017	-10000	0	-10000	0	0

×

Thromboxane A2 receptor signaling

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
TGM2	0.004	0.047	-10000	0	-0.5	4	4
GNB1/GNG2	-0.039	0.072	-10000	0	-0.18	89	89
AKT1	-0.002	0.1	-10000	0	-0.2	90	90
EGF	-0.091	0.21	-10000	0	-0.51	90	90
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.011	0.085	-10000	0	-0.41	9	9
mol:Ca2+	-0.021	0.14	-10000	0	-0.3	91	91
LYN	0.028	0.049	-10000	0	-0.37	4	4
RhoA/GTP	-0.026	0.048	-10000	0	-0.14	16	16
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.025	0.16	-10000	0	-0.34	91	91
GNG2	0.008	0.033	-10000	0	-0.5	2	2
ARRB2	0.01	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.023	0.043	-10000	0	-0.33	3	3
G beta5/gamma2	-0.05	0.093	-10000	0	-0.23	89	89
PRKCH	-0.027	0.16	-10000	0	-0.34	91	91
DNM1	0.003	0.059	-10000	0	-0.51	6	6
TXA2/TP beta/beta Arrestin3	-0.003	0.017	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	-0.002	0.077	-10000	0	-0.5	11	11
G12 family/GTP	-0.063	0.12	-10000	0	-0.3	91	91
ADRBK1	0.01	0	-10000	0	-10000	0	0
ADRBK2	0.009	0.024	-10000	0	-0.5	1	1
RhoA/GTP/ROCK1	0	0	-10000	0	-10000	0	0
mol:GDP	0.005	0.095	0.34	10	-10000	0	10
mol:NADP	-0.003	0.082	-10000	0	-0.51	12	12
RAB11A	0.01	0	-10000	0	-10000	0	0
PRKG1	-0.046	0.16	-10000	0	-0.5	51	51
mol:IP3	-0.033	0.18	-10000	0	-0.37	91	91
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	-0.056	0.23	-10000	0	-0.51	91	91
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.007	0.093	-10000	0	-0.37	5	5
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.019	0.072	-10000	0	-0.4	8	8
RHOA	0.01	0	-10000	0	-10000	0	0
PTGIR	0	0.07	-10000	0	-0.5	9	9
PRKCB1	-0.034	0.17	-10000	0	-0.37	91	91
GNAQ	0.009	0.024	-10000	0	-0.5	1	1
mol:L-citrulline	-0.003	0.082	-10000	0	-0.51	12	12
TXA2/TXA2-R family	-0.058	0.23	-10000	0	-0.52	91	91
LCK	0.027	0.055	-10000	0	-0.37	6	6
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.01	0.053	-10000	0	-0.5	3	3
TXA2-R family/G12 family/GDP/G beta/gamma	0.022	0.021	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.009	0.05	-10000	0	-0.49	3	3
MAPK14	-0.006	0.11	-10000	0	-0.22	89	89
TGM2/GTP	-0.04	0.19	-10000	0	-0.41	91	91
MAPK11	-0.007	0.11	-10000	0	-0.22	89	89
ARHGEF1	-0.006	0.086	-10000	0	-0.18	40	40
GNAI2	0.01	0	-10000	0	-10000	0	0
JNK cascade	-0.034	0.18	-10000	0	-0.38	91	91
RAB11/GDP	0.01	0.001	-10000	0	-10000	0	0
ICAM1	-0.02	0.14	-10000	0	-0.28	89	89
cAMP biosynthetic process	-0.033	0.16	-10000	0	-0.34	91	91
Gq family/GTP/EBP50	0.015	0.048	-10000	0	-0.34	4	4
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0.028	0.049	-10000	0	-0.37	4	4
GNB5	0.01	0	-10000	0	-10000	0	0
GNB1	0.01	0	-10000	0	-10000	0	0
EGF/EGFR	0.008	0.078	-10000	0	-0.32	12	12
VCAM1	-0.021	0.14	-10000	0	-0.29	89	89
TP beta/Gq family/GDP/G beta5/gamma2	0.023	0.043	-10000	0	-0.33	3	3
platelet activation	-0.009	0.15	-10000	0	-0.29	91	91
PGI2/IP	-0.007	0.05	-10000	0	-0.36	9	9
PRKACA	0.005	0.066	-10000	0	-0.31	17	17
Gq family/GDP/G beta5/gamma2	0.021	0.045	-10000	0	-0.28	6	6
TXA2/TP beta/beta Arrestin2	-0.002	0.014	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.011	0.063	-10000	0	-0.57	3	3
mol:DAG	-0.04	0.19	-10000	0	-0.41	91	91
EGFR	-0.006	0.088	-10000	0	-0.51	14	14
TXA2/TP alpha	-0.05	0.22	-10000	0	-0.47	91	91
Gq family/GTP	-0.008	0.05	-10000	0	-0.24	16	16
YES1	0.028	0.049	-10000	0	-0.37	4	4
GNAI2/GTP	-0.009	0.049	-10000	0	-0.43	4	4
PGD2/DP	-0.008	0.055	-10000	0	-0.36	11	11
SLC9A3R1	0.008	0.034	-10000	0	-0.51	2	2
FYN	0.028	0.05	-10000	0	-0.37	4	4
mol:NO	-0.003	0.082	-10000	0	-0.51	12	12
GNA15	0.01	0	-10000	0	-10000	0	0
PGK/cGMP	-0.04	0.11	-10000	0	-0.31	61	61
RhoA/GDP	0.01	0.001	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.011	0.058	-10000	0	-0.46	5	5
NOS3	-0.003	0.082	-10000	0	-0.51	12	12
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCA	-0.028	0.16	-10000	0	-0.34	92	92
PRKCB	-0.03	0.17	-10000	0	-0.35	93	93
PRKCE	-0.027	0.16	-10000	0	-0.34	92	92
PRKCD	-0.032	0.17	-10000	0	-0.37	91	91
PRKCG	-0.043	0.18	-10000	0	-0.39	91	91
muscle contraction	-0.05	0.22	-10000	0	-0.48	91	91
PRKCZ	-0.025	0.16	-10000	0	-0.34	91	91
ARR3	0	0.034	-10000	0	-0.51	2	2
TXA2/TP beta	-0.01	0.055	-10000	0	-0.49	4	4
PRKCQ	-0.05	0.18	-10000	0	-0.38	93	93
MAPKKK cascade	-0.048	0.21	-10000	0	-0.45	91	91
SELE	-0.041	0.18	-10000	0	-0.39	89	89
TP beta/GNAI2/GDP/G beta/gamma	-0.009	0.053	-10000	0	-0.47	4	4
ROCK1	0.01	0	-10000	0	-10000	0	0
GNA14	-0.005	0.087	-10000	0	-0.5	14	14
chemotaxis	-0.071	0.26	-10000	0	-0.6	90	90
GNA12	0.01	0	-10000	0	-10000	0	0
GNA13	0.01	0	-10000	0	-10000	0	0
GNA11	0.008	0.033	-10000	0	-0.5	2	2
Rac1/GTP	0	0	-10000	0	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.026	0.025	-9999	-10000	0	0
VDR	0.008	0.034	-9999	-0.51	2	2
FAM120B	0.01	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.092	0.14	-9999	-0.46	11	11
RXRs/LXRs/DNA/Oxysterols	-0.074	0.14	-9999	-0.48	20	20
MED1	0.01	0	-9999	-10000	0	0
mol:9cRA	0.003	0.009	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	0.003	0.078	-9999	-0.46	1	1
RXRs/NUR77	-0.17	0.18	-9999	-0.48	61	61
RXRs/PPAR	-0.13	0.16	-9999	-0.43	47	47
NCOR2	0.01	0	-9999	-10000	0	0
VDR/VDR/Vit D3	-0.002	0.024	-9999	-0.37	2	2
RARs/VDR/DNA/Vit D3	-0.002	0.022	-9999	-10000	0	0
RARA	0.01	0	-9999	-10000	0	0
NCOA1	0.01	0	-9999	-10000	0	0
VDR/VDR/DNA	0.008	0.034	-9999	-0.51	2	2
RARs/RARs/DNA/9cRA	-0.001	0.017	-9999	-0.25	2	2
RARG	0.01	0	-9999	-10000	0	0
RPS6KB1	0.043	0.04	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	0.003	0.078	-9999	-0.46	1	1
THRA	0.01	0	-9999	-10000	0	0
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	-0.002	0.024	-9999	-0.37	2	2
RXRs/PPAR/9cRA/PGJ2/DNA	-0.12	0.14	-9999	-0.26	242	242
NR1H4	-0.03	0.13	-9999	-0.51	32	32
RXRs/LXRs/DNA	-0.095	0.14	-9999	-0.39	11	11
NR1H2	0.013	0.007	-9999	-10000	0	0
NR1H3	0.013	0.008	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.11	0.14	-9999	-0.32	13	13
NR4A1	-0.094	0.2	-9999	-0.5	95	95
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.097	0.12	-9999	-0.31	28	28
RXRG	-0.25	0.26	-9999	-0.5	242	242
RXR alpha/CCPG	0.017	0.004	-9999	-10000	0	0
RXRA	0.013	0.007	-9999	-10000	0	0
RXRB	0.013	0.008	-9999	-10000	0	0
THRB	-0.041	0.15	-9999	-0.5	47	47
PPARG	-0.053	0.17	-9999	-0.5	58	58
PPARD	0.01	0	-9999	-10000	0	0
TNF	-0.085	0.22	-9999	-1	19	19
mol:Oxysterols	0.003	0.009	-9999	-10000	0	0
cholesterol transport	-0.073	0.14	-9999	-0.48	20	20
PPARA	0.01	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	0.008	0.033	-9999	-0.5	2	2
RXRs/NUR77/BCL2	-0.15	0.16	-9999	-0.27	289	289
SREBF1	-0.061	0.13	-9999	-0.53	11	11
RXRs/RXRs/DNA/9cRA	-0.12	0.15	-9999	-0.26	242	242
ABCA1	-0.063	0.14	-9999	-0.62	12	12
RARs/THRs	-0.025	0.074	-9999	-0.49	1	1
RXRs/FXR	-0.14	0.16	-9999	-0.29	147	147
BCL2	0.007	0.041	-9999	-0.51	3	3

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	-0.002	0.023	-10000	0	-0.35	2	2
Necdin/E2F1	-0.01	0.059	-10000	0	-0.36	13	13
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.029	0.078	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/BEX1	-0.12	0.16	-10000	0	-0.32	171	171
NT-4/5 (dimer)/p75(NTR)	-0.03	0.1	-10000	0	-0.37	38	38
IKBKB	0.01	0	-10000	0	-10000	0	0
AKT1	0.002	0.083	-10000	0	-10000	0	0
IKBKG	0.01	0	-10000	0	-10000	0	0
BDNF	-0.25	0.26	-10000	0	-0.5	241	241
MGDIs/NGR/p75(NTR)/LINGO1	-0.05	0.12	-10000	0	-0.31	75	75
FURIN	-0.005	0.086	-10000	0	-0.51	13	13
proBDNF (dimer)/p75(NTR)/Sortilin	-0.16	0.15	-10000	0	-0.3	250	250
LINGO1	-0.059	0.18	-10000	0	-0.51	62	62
Sortilin/TRAF6/NRIF	-0.002	0.02	-10000	0	-10000	0	0
proBDNF (dimer)	-0.25	0.26	-10000	0	-0.5	241	241
NTRK1	-0.012	0.1	-10000	0	-0.5	20	20
RTN4R	0.009	0.024	-10000	0	-0.5	1	1
neuron apoptosis	-0.11	0.14	-10000	0	-0.4	31	31
IRAK1	0.009	0.024	-10000	0	-0.51	1	1
SHC1	-0.011	0.098	-10000	0	-0.3	49	49
ARHGDIA	0.01	0	-10000	0	-10000	0	0
RhoA/GTP	0	0	-10000	0	-10000	0	0
Gamma Secretase	-0.002	0.019	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.029	0.082	-10000	0	-0.27	28	28
MAGEH1	0.01	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.032	0.089	-10000	0	-0.27	55	55
Mammalian IAPs/DIABLO	-0.003	0.03	-10000	0	-0.27	4	4
proNGF (dimer)	-0.028	0.13	-10000	0	-0.51	34	34
MAGED1	0.009	0.024	-10000	0	-0.51	1	1
APP	0.01	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.017	0.12	-10000	0	-0.5	25	25
ZNF274	0.01	0	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.026	0.075	-10000	0	-0.24	49	49
NGF	-0.028	0.13	-10000	0	-0.51	34	34
cell cycle arrest	0.013	0.11	-10000	0	-0.29	20	20
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.009	0.062	-10000	0	-0.22	22	22
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.025	0.086	-10000	0	-0.31	38	38
NCSTN	0.01	0	-10000	0	-10000	0	0
mol:GTP	-0.032	0.092	-10000	0	-0.3	50	50
PSENEN	0.009	0.024	-10000	0	-0.51	1	1
mol:ceramide	-0.005	0.089	-10000	0	-0.26	28	28
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.015	0.057	-10000	0	-0.39	1	1
p75(NTR)/beta APP	-0.011	0.063	-10000	0	-0.36	15	15
BEX1	-0.14	0.23	-10000	0	-0.5	139	139
mol:GDP	-0.019	0.097	-10000	0	-0.3	49	49
NGF (dimer)	-0.083	0.13	-10000	0	-0.3	84	84
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.044	0.1	-10000	0	-0.28	75	75
PIK3R1	0.009	0.024	-10000	0	-0.5	1	1
RAC1/GTP	-0.026	0.077	-10000	0	-0.25	49	49
MYD88	0.01	0	-10000	0	-10000	0	0
CHUK	0.01	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.032	0.092	-10000	0	-0.3	50	50
RHOB	0.01	0	-10000	0	-10000	0	0
RHOA	0.01	0	-10000	0	-10000	0	0
MAGE-G1/E2F1	-0.005	0.044	-10000	0	-0.36	7	7
NT3 (dimer)	-0.02	0.12	-10000	0	-0.5	27	27
TP53	-0.1	0.14	-10000	0	-0.46	8	8
PRDM4	-0.005	0.09	-10000	0	-0.26	51	51
BDNF (dimer)	-0.3	0.22	-10000	0	-0.57	143	143
PIK3CA	0.01	0	-10000	0	-10000	0	0
SORT1	0.008	0.033	-10000	0	-0.5	2	2
activation of caspase activity	-0.028	0.077	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.029	0.082	-10000	0	-0.26	51	51
RHOC	0.01	0	-10000	0	-10000	0	0
XIAP	0.01	0	-10000	0	-10000	0	0
MAPK10	-0.096	0.15	-10000	0	-0.4	51	51
DIABLO	0.01	0	-10000	0	-10000	0	0
SMPD2	-0.005	0.09	-10000	0	-0.27	28	28
APH1B	0.008	0.033	-10000	0	-0.5	2	2
APH1A	0.01	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.032	0.093	-10000	0	-0.3	51	51
PSEN1	0.01	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.031	0.11	-10000	0	-0.39	38	38
MAPK8	-0.073	0.12	-10000	0	-0.37	26	26
MAPK9	-0.073	0.12	-10000	0	-0.36	28	28
APAF1	0.01	0	-10000	0	-10000	0	0
NTF3	-0.02	0.12	-10000	0	-0.5	27	27
NTF4	-0.017	0.12	-10000	0	-0.5	25	25
NDN	0.003	0.057	-10000	0	-0.5	6	6
RAC1/GDP	0	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.023	0.067	-10000	0	-10000	0	0
p75 CTF/Sortilin/TRAF6/NRIF	-0.001	0.017	-10000	0	-0.26	2	2
RhoA-B-C/GTP	-0.032	0.091	-10000	0	-0.3	50	50
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.13	0.13	-10000	0	-0.49	8	8
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.14	0.14	-10000	0	-0.42	13	13
PRKACB	0.009	0.024	-10000	0	-0.51	1	1
proBDNF (dimer)/p75 ECD	-0.18	0.18	-10000	0	-0.35	241	241
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.003	0.058	-10000	0	-0.51	6	6
BIRC2	0.01	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.02	0.11	0.18	102	-0.27	14	116
BAD	-0.076	0.13	-10000	0	-0.38	29	29
RIPK2	0.01	0	-10000	0	-10000	0	0
NGFR	-0.007	0.091	-10000	0	-0.51	15	15
CYCS	0.001	0.087	-10000	0	-0.49	1	1
ADAM17	0.01	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.028	0.081	-10000	0	-0.26	49	49
BCL2L11	-0.076	0.13	-10000	0	-0.38	29	29
BDNF (dimer)/p75(NTR)	-0.19	0.18	-10000	0	-0.36	250	250
PI3K	-0.028	0.081	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.029	0.082	-10000	0	-0.27	27	27
NDNL2	0.01	0	-10000	0	-10000	0	0
YWHAE	0.01	0	-10000	0	-10000	0	0
PRKCI	0.01	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.038	0.11	-10000	0	-0.36	49	49
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.029	0.084	-10000	0	-0.28	29	29
TRAF6	0.01	0	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCZ	0.007	0.041	-10000	0	-0.5	3	3
PLG	-0.008	0.071	-10000	0	-0.51	9	9
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.13	0.16	-10000	0	-0.47	32	32
SQSTM1	0.009	0.024	-10000	0	-0.51	1	1
NGFRAP1	0.004	0.052	-10000	0	-0.5	5	5
CASP3	-0.069	0.12	-10000	0	-0.38	22	22
E2F1	0.002	0.064	-10000	0	-0.51	7	7
CASP9	0.01	0	-10000	0	-10000	0	0
IKK complex	-0.026	0.069	-10000	0	-0.39	3	3
NGF (dimer)/TRKA	-0.041	0.12	-10000	0	-0.36	53	53
MMP7	-0.087	0.2	-10000	0	-0.51	87	87
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.026	0.075	-10000	0	-10000	0	0
MMP3	-0.2	0.26	-10000	0	-0.51	184	184
APAF-1/Caspase 9	-0.021	0.057	-10000	0	-0.37	2	2

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.042	0.11	-10000	0	-0.31	63	63
fibroblast growth factor receptor signaling pathway	-0.042	0.11	-10000	0	-0.31	63	63
LAMA1	-0.019	0.12	-10000	0	-0.51	26	26
PRNP	0.008	0.033	-10000	0	-0.5	2	2
GPC1/SLIT2	-0.09	0.16	-10000	0	-0.36	118	118
SMAD2	0.019	0.047	-10000	0	-10000	0	0
GPC1/PrPc/Cu2+	-0.003	0.031	-10000	0	-0.3	5	5
GPC1/Laminin alpha1	-0.022	0.089	-10000	0	-0.37	28	28
TDGF1	-0.02	0.12	-10000	0	-0.51	26	26
CRIPTO/GPC1	-0.022	0.087	-10000	0	-0.36	29	29
APP/GPC1	-0.002	0.028	-10000	0	-0.35	3	3
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0.002	0.077	-10000	0	-0.3	29	29
FLT1	0.01	0	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	-0.008	0.048	-10000	0	-0.29	13	13
SERPINC1	-0.001	0.068	-10000	0	-0.51	8	8
FYN	0.001	0.08	-10000	0	-0.31	29	29
FGR	-0.022	0.12	-10000	0	-0.32	60	60
positive regulation of MAPKKK cascade	-0.016	0.12	-10000	0	-0.38	29	29
SLIT2	-0.12	0.22	-10000	0	-0.5	116	116
GPC1/NRG	-0.074	0.15	-10000	0	-0.36	96	96
NRG1	-0.094	0.2	-10000	0	-0.5	95	95
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.002	0.023	-10000	0	-0.29	3	3
LYN	0.002	0.077	-10000	0	-0.3	29	29
mol:Spermine	0.007	0.03	-10000	0	-0.36	3	3
cell growth	-0.042	0.11	-10000	0	-0.31	63	63
BMP signaling pathway	-0.007	0.041	0.5	3	-10000	0	3
SRC	0.002	0.077	-10000	0	-0.3	29	29
TGFBR1	0.009	0.024	-10000	0	-0.51	1	1
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.07	0.19	-10000	0	-0.5	73	73
GPC1	0.007	0.041	-10000	0	-0.5	3	3
TGFBR1 (dimer)	0.009	0.024	-10000	0	-0.51	1	1
VEGFA	0.01	0	-10000	0	-10000	0	0
BLK	-0.048	0.14	-10000	0	-0.31	99	99
HCK	-0.011	0.099	-10000	0	-0.31	46	46
FGF2	-0.057	0.17	-10000	0	-0.5	61	61
FGFR1	0.007	0.041	-10000	0	-0.5	3	3
VEGFR1 homodimer	0.01	0	-10000	0	-10000	0	0
TGFBR2	0	0.07	-10000	0	-0.5	9	9
cell death	-0.002	0.028	-10000	0	-0.35	3	3
ATIII/GPC1	-0.009	0.055	-10000	0	-0.36	11	11
PLA2G2A/GPC1	-0.058	0.13	-10000	0	-0.36	75	75
LCK	-0.001	0.08	-10000	0	-0.3	32	32
neuron differentiation	-0.074	0.15	-10000	0	-0.36	96	96
PrPc/Cu2+	-0.002	0.024	-10000	0	-0.36	2	2
APP	0.01	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	0	0.07	-10000	0	-0.5	9	9

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	-0.008	0.054	-9999	-0.35	11	11
alphaV beta3 Integrin	-0.055	0.12	-9999	-0.31	84	84
PTK2	-0.056	0.16	-9999	-0.44	36	36
IGF1R	0.008	0.033	-9999	-0.5	2	2
PI4KB	0.01	0	-9999	-10000	0	0
MFGE8	0.01	0	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
CDKN1B	-0.1	0.2	-9999	-0.51	81	81
VEGFA	0.01	0	-9999	-10000	0	0
ILK	-0.1	0.2	-9999	-0.51	81	81
ROCK1	0.01	0	-9999	-10000	0	0
AKT1	-0.094	0.18	-9999	-0.47	80	80
PTK2B	0.008	0.079	-9999	-0.49	2	2
alphaV/beta3 Integrin/JAM-A	-0.09	0.15	-9999	-0.52	29	29
CBL	0.01	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.033	0.094	-9999	-0.3	51	51
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.007	0.046	-9999	-0.28	12	12
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.018	0.098	-9999	-0.37	9	9
alphaV/beta3 Integrin/Syndecan-1	-0.017	0.07	-9999	-0.3	27	27
PI4KA	0.01	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.048	0.11	-9999	-0.54	10	10
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.24	0.15	-9999	-0.32	345	345
RPS6KB1	-0.008	0.12	-9999	-0.5	10	10
TLN1	0.009	0.024	-9999	-0.5	1	1
MAPK3	-0.091	0.19	-9999	-0.52	64	64
GPR124	0.007	0.041	-9999	-0.5	3	3
MAPK1	-0.091	0.19	-9999	-0.52	64	64
PXN	0.01	0	-9999	-10000	0	0
PIK3R1	0.009	0.024	-9999	-0.5	1	1
alphaV/beta3 Integrin/Tumstatin	-0.1	0.15	-9999	-0.3	154	154
cell adhesion	-0.025	0.07	-9999	-0.28	5	5
ANGPTL3	-0.021	0.12	-9999	-0.51	24	24
VEGFR2 homodimer/VEGFA homodimer/Src	-0.007	0.044	-9999	-0.29	11	11
IGF-1R heterotetramer	0.008	0.033	-9999	-0.5	2	2
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	0	0.07	-9999	-0.5	9	9
ITGB3	-0.02	0.12	-9999	-0.51	27	27
IGF1	-0.001	0.074	-9999	-0.5	10	10
RAC1	0.01	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.019	0.077	-9999	-0.32	28	28
apoptosis	0.01	0	-9999	-10000	0	0
CD47	0.008	0.033	-9999	-0.5	2	2
alphaV/beta3 Integrin/CD47	-0.019	0.072	-9999	-0.3	29	29
VCL	0.01	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.041	0.11	-9999	-0.32	61	61
CSF1	0.004	0.052	-9999	-0.5	5	5
PIK3C2A	-0.1	0.2	-9999	-0.51	81	81
PI4 Kinase/Pyk2	-0.078	0.13	-9999	-0.45	32	32
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.021	0.074	-9999	-0.27	37	37
FAK1/Vinculin	-0.04	0.13	-9999	-0.35	35	35
alphaV beta3/Integrin/ppsTEM5	-0.019	0.078	-9999	-0.32	28	28
RHOA	0.01	0	-9999	-10000	0	0
VTN	-0.084	0.2	-9999	-0.5	86	86
BCAR1	0.009	0.024	-9999	-0.5	1	1
FGF2	-0.057	0.17	-9999	-0.5	61	61
F11R	-0.031	0.13	-9999	-0.35	62	62
alphaV/beta3 Integrin/Lactadherin	-0.017	0.07	-9999	-0.3	27	27
alphaV/beta3 Integrin/TGFBR2	-0.023	0.079	-9999	-0.3	36	36
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.003	0.029	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.016	0.067	-9999	-0.28	27	27
mol:GDP	0	0	-9999	-10000	0	0
FN1	0.005	0.047	-9999	-0.5	4	4
alphaV/beta3 Integrin/Pyk2	-0.021	0.071	-9999	-0.49	2	2
SDC1	0.01	0	-9999	-10000	0	0
VAV3	0.024	0.046	-9999	-0.49	1	1
PTPN11	0.01	0	-9999	-10000	0	0
IRS1	0.009	0.024	-9999	-0.5	1	1
FAK1/Paxillin	-0.04	0.13	-9999	-0.34	36	36
cell migration	-0.03	0.12	-9999	-0.36	16	16
ITGAV	0.01	0	-9999	-10000	0	0
PI3K	-0.08	0.13	-9999	-0.47	29	29
SPP1	-0.37	0.23	-9999	-0.51	339	339
KDR	-0.002	0.077	-9999	-0.5	11	11
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.01	0	-9999	-10000	0	0
COL4A3	-0.14	0.23	-9999	-0.5	133	133
angiogenesis	-0.07	0.21	-9999	-0.53	64	64
Rac1/GTP	-0.005	0.037	-9999	-0.45	1	1
EDIL3	-0.033	0.14	-9999	-0.5	39	39
cell proliferation	-0.023	0.079	-9999	-0.3	36	36

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	-0.09	0.17	-9999	-0.37	121	121
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.04	0.11	-9999	-0.36	52	52
STXBP1	0.007	0.041	-9999	-0.5	3	3
ACh/CHRNA1	-0.033	0.098	-9999	-0.35	39	39
RAB3GAP2/RIMS1/UNC13B	-0.033	0.093	-9999	-0.3	52	52
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	-0.048	0.16	-9999	-0.5	52	52
mol:ACh	-0.016	0.04	-9999	-0.077	132	132
RAB3GAP2	0.01	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.08	0.11	-9999	-0.37	23	23
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.033	0.098	-9999	-0.34	39	39
UNC13B	0.01	0	-9999	-10000	0	0
CHRNA1	-0.034	0.14	-9999	-0.51	39	39
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.034	0.1	-9999	-0.36	41	41
SNAP25	-0.002	0.039	-9999	-0.18	20	20
VAMP2	0.005	0	-9999	-10000	0	0
SYT1	-0.036	0.15	-9999	-0.51	41	41
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.071	0.14	-9999	-0.31	124	124
STX1A/SNAP25 fragment 1/VAMP2	-0.08	0.11	-9999	-0.37	23	23

×

Syndecan-1-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
TGFB1	0.01	0	-9999	-10000	0	0
CCL5	0.004	0.052	-9999	-0.5	5	5
SDCBP	0.01	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.11	0.11	-9999	-0.34	27	27
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.1	0.11	-9999	-0.33	31	31
Syndecan-1/Syntenin	-0.1	0.1	-9999	-0.32	27	27
MAPK3	-0.08	0.096	-9999	-0.49	2	2
HGF/MET	-0.042	0.12	-9999	-0.37	52	52
TGFB1/TGF beta receptor Type II	0.01	0	-9999	-10000	0	0
BSG	0.01	0	-9999	-10000	0	0
keratinocyte migration	-0.1	0.1	-9999	-0.32	31	31
Syndecan-1/RANTES	-0.1	0.1	-9999	-0.32	31	31
Syndecan-1/CD147	-0.091	0.1	-9999	-0.38	5	5
Syndecan-1/Syntenin/PIP2	-0.1	0.087	-9999	-0.3	27	27
LAMA5	0.005	0.047	-9999	-0.5	4	4
positive regulation of cell-cell adhesion	-0.1	0.085	-9999	-0.3	27	27
MMP7	-0.087	0.2	-9999	-0.51	87	87
HGF	-0.019	0.12	-9999	-0.5	26	26
Syndecan-1/CASK	-0.11	0.1	-9999	-0.32	27	27
Syndecan-1/HGF/MET	-0.12	0.13	-9999	-0.42	41	41
regulation of cell adhesion	-0.072	0.093	-9999	-0.47	2	2
HPSE	0.008	0.034	-9999	-0.51	2	2
positive regulation of cell migration	-0.11	0.11	-9999	-0.34	27	27
SDC1	-0.11	0.11	-9999	-0.34	27	27
Syndecan-1/Collagen	-0.11	0.11	-9999	-0.34	27	27
PPIB	0.009	0.024	-9999	-0.51	1	1
MET	-0.022	0.12	-9999	-0.51	29	29
PRKACA	0.01	0	-9999	-10000	0	0
MMP9	-0.094	0.21	-9999	-0.51	93	93
MAPK1	-0.08	0.096	-9999	-0.49	2	2
homophilic cell adhesion	-0.11	0.11	-9999	-0.34	27	27
MMP1	-0.34	0.25	-9999	-0.51	313	313

×

Ephrin B reverse signaling

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
EFNB2	0.001	0.066	-10000	0	-0.5	8	8
EPHB2	-0.049	0.16	-10000	0	-0.51	53	53
EFNB1	0.011	0.052	-10000	0	-0.36	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.058	0.12	-10000	0	-0.49	15	15
Ephrin B2/EPHB1-2	-0.064	0.13	-10000	0	-0.29	104	104
neuron projection morphogenesis	-0.056	0.11	-10000	0	-0.47	15	15
Ephrin B1/EPHB1-2/Tiam1	-0.059	0.13	-10000	0	-0.53	15	15
DNM1	0.003	0.059	-10000	0	-0.51	6	6
cell-cell signaling	0.001	0.002	-10000	0	-10000	0	0
MAP2K4	-0.045	0.18	-10000	0	-0.58	48	48
YES1	-0.081	0.24	-10000	0	-0.8	48	48
Ephrin B1/EPHB1-2/NCK2	-0.055	0.12	-10000	0	-0.5	13	13
PI3K	-0.046	0.18	-10000	0	-0.59	48	48
mol:GDP	-0.059	0.13	-10000	0	-0.52	15	15
ITGA2B	-0.042	0.15	-10000	0	-0.5	47	47
endothelial cell proliferation	-0.005	0.039	-10000	0	-0.3	8	8
FYN	-0.082	0.24	-10000	0	-0.8	48	48
MAP3K7	-0.063	0.19	-10000	0	-0.62	48	48
FGR	-0.093	0.25	-10000	0	-0.82	48	48
TIAM1	0.001	0.066	-10000	0	-0.5	8	8
PIK3R1	0.009	0.024	-10000	0	-0.5	1	1
RGS3	0.01	0	-10000	0	-10000	0	0
cell adhesion	-0.07	0.2	-10000	0	-0.58	48	48
LYN	-0.081	0.24	-10000	0	-0.8	48	48
Ephrin B1/EPHB1-2/Src Family Kinases	-0.076	0.23	-10000	0	-0.74	48	48
Ephrin B1/EPHB1-2	-0.071	0.2	-10000	0	-0.67	48	48
SRC	-0.081	0.24	-10000	0	-0.8	48	48
ITGB3	-0.02	0.12	-10000	0	-0.51	27	27
EPHB1	-0.049	0.17	-10000	0	-0.51	53	53
EPHB4	0.01	0	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	-0.005	0.039	-10000	0	-0.3	8	8
alphaIIb/beta3 Integrin	-0.056	0.13	-10000	0	-0.36	73	73
BLK	-0.086	0.24	-10000	0	-0.81	48	48
HCK	-0.087	0.25	-10000	0	-0.82	48	48
regulation of stress fiber formation	0.055	0.12	0.49	13	-10000	0	13
MAPK8	-0.036	0.17	-10000	0	-0.55	48	48
Ephrin B1/EPHB1-2/RGS3	-0.055	0.12	-10000	0	-0.5	13	13
endothelial cell migration	-0.055	0.17	-10000	0	-0.53	49	49
NCK2	0.01	0	-10000	0	-10000	0	0
PTPN13	-0.057	0.19	-10000	0	-0.61	48	48
regulation of focal adhesion formation	0.055	0.12	0.49	13	-10000	0	13
chemotaxis	0.055	0.12	0.49	13	-10000	0	13
PIK3CA	0.01	0	-10000	0	-10000	0	0
Rac1/GTP	-0.057	0.12	-10000	0	-0.48	15	15
angiogenesis	-0.071	0.2	-10000	0	-0.67	48	48
LCK	-0.082	0.24	-10000	0	-0.8	48	48

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.01	0	-9999	-10000	0	0
EGFR	-0.006	0.088	-9999	-0.51	14	14
EGF/EGFR	-0.089	0.14	-9999	-0.27	153	153
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.054	0.1	-9999	-0.5	3	3
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.008	0.033	-9999	-0.5	2	2
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.091	0.21	-9999	-0.51	90	90
EGF/EGFR dimer/SHC	-0.067	0.13	-9999	-0.31	101	101
mol:GDP	-0.054	0.1	-9999	-0.49	3	3
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.065	0.18	-9999	-0.5	69	69
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.049	0.095	-9999	-0.46	3	3
SHC1	0.01	0	-9999	-10000	0	0
HRAS/GDP	-0.05	0.097	-9999	-0.46	3	3
FRAP1	-0.028	0.11	-9999	-0.47	3	3
EGF/EGFR dimer	-0.08	0.16	-9999	-0.37	101	101
SOS1	0.01	0	-9999	-10000	0	0
GRB2	0.01	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.054	0.13	-9999	-0.35	71	71

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.01	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.039	0.076	-10000	0	-0.28	17	17
NT3 (dimer)/TRKC	-0.09	0.17	-10000	0	-0.39	108	108
NT3 (dimer)/TRKB	-0.13	0.17	-10000	0	-0.32	189	189
SHC/Grb2/SOS1/GAB1/PI3K	0.028	0.016	-10000	0	-10000	0	0
RAPGEF1	0.01	0	-10000	0	-10000	0	0
BDNF	-0.25	0.26	-10000	0	-0.5	241	241
PIK3CA	0.01	0	-10000	0	-10000	0	0
DYNLT1	0.01	0	-10000	0	-10000	0	0
NTRK1	-0.012	0.1	-10000	0	-0.5	20	20
NTRK2	-0.17	0.24	-10000	0	-0.5	168	168
NTRK3	-0.093	0.2	-10000	0	-0.5	94	94
NT-4/5 (dimer)/TRKB	-0.13	0.17	-10000	0	-0.33	185	185
neuron apoptosis	0.2	0.2	0.49	116	-10000	0	116
SHC 2-3/Grb2	-0.22	0.22	-10000	0	-0.57	104	104
SHC1	0.01	0	-10000	0	-10000	0	0
SHC2	-0.14	0.14	-10000	0	-0.44	53	53
SHC3	-0.22	0.26	-10000	0	-0.64	111	111
STAT3 (dimer)	0.012	0.038	-10000	0	-0.33	6	6
NT3 (dimer)/TRKA	-0.039	0.11	-10000	0	-0.32	57	57
RIN/GDP	-0.024	0.076	-10000	0	-0.24	10	10
GIPC1	0.01	0	-10000	0	-10000	0	0
KRAS	0.01	0	-10000	0	-10000	0	0
DNAJA3	-0.027	0.07	-10000	0	-0.32	9	9
RIN/GTP	-0.002	0.03	-10000	0	-0.37	3	3
CCND1	0.015	0.085	-10000	0	-0.73	6	6
MAGED1	0.009	0.024	-10000	0	-0.51	1	1
PTPN11	0.01	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.017	0.12	-10000	0	-0.5	25	25
SHC/GRB2/SOS1	0	0	-10000	0	-10000	0	0
GRB2	0.01	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.047	0.12	-10000	0	-0.33	66	66
TRKA/NEDD4-2	-0.015	0.072	-10000	0	-0.35	20	20
ELMO1	0.004	0.053	-10000	0	-0.5	5	5
RhoG/GTP/ELMO1/DOCK1	-0.003	0.031	-10000	0	-0.3	5	5
NGF	-0.028	0.13	-10000	0	-0.51	34	34
HRAS	0.01	0	-10000	0	-10000	0	0
DOCK1	0.01	0	-10000	0	-10000	0	0
GAB2	0.005	0.047	-10000	0	-0.5	4	4
RIT2	-0.002	0.041	-10000	0	-0.51	3	3
RIT1	0.01	0	-10000	0	-10000	0	0
FRS2	0.008	0.034	-10000	0	-0.51	2	2
DNM1	0.003	0.059	-10000	0	-0.51	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.01	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.028	0.075	-10000	0	-0.32	13	13
mol:GDP	-0.035	0.11	-10000	0	-0.31	14	14
NGF (dimer)	-0.028	0.13	-10000	0	-0.51	34	34
RhoG/GDP	-0.004	0.037	-10000	0	-0.36	5	5
RIT1/GDP	-0.019	0.075	-10000	0	-0.22	7	7
TIAM1	0.001	0.066	-10000	0	-0.5	8	8
PIK3R1	0.009	0.024	-10000	0	-0.5	1	1
BDNF (dimer)/TRKB	-0.25	0.2	-10000	0	-0.38	315	315
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2	-0.001	0.02	-10000	0	-0.3	2	2
SHC/GRB2/SOS1/GAB1	-0.001	0.012	-10000	0	-0.26	1	1
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.02	0.12	-10000	0	-0.5	27	27
RAP1/GDP	-0.031	0.052	-10000	0	-0.22	2	2
KIDINS220/CRKL	0.01	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.25	0.26	-10000	0	-0.5	241	241
ubiquitin-dependent protein catabolic process	-0.034	0.096	-10000	0	-0.3	53	53
Schwann cell development	-0.047	0.034	-10000	0	-10000	0	0
EHD4	0.01	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	-0.001	0.017	-10000	0	-0.27	2	2
FRS2 family/SHP2/CRK family/C3G/GAB2	0.03	0.021	-10000	0	-10000	0	0
RAP1B	0.01	0	-10000	0	-10000	0	0
RAP1A	0.01	0	-10000	0	-10000	0	0
CDC42/GTP	-0.24	0.21	-10000	0	-0.5	156	156
ABL1	0.01	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
Rap1/GTP	-0.091	0.073	-10000	0	-10000	0	0
STAT3	0.012	0.038	-10000	0	-0.32	6	6
axon guidance	-0.23	0.2	-10000	0	-0.48	156	156
MAPK3	-0.019	0.12	-10000	0	-0.3	66	66
MAPK1	-0.019	0.12	-10000	0	-0.3	66	66
CDC42/GDP	-0.019	0.075	-10000	0	-0.22	10	10
NTF3	-0.02	0.12	-10000	0	-0.5	27	27
NTF4	-0.017	0.12	-10000	0	-0.5	25	25
NGF (dimer)/TRKA/FAIM	-0.034	0.096	-10000	0	-0.3	53	53
PI3K	-0.001	0.016	-10000	0	-0.35	1	1
FRS3	0.01	0	-10000	0	-10000	0	0
FAIM	0.01	0	-10000	0	-10000	0	0
GAB1	0.009	0.024	-10000	0	-0.5	1	1
RASGRF1	-0.12	0.14	-10000	0	-0.42	45	45
SOS1	0.01	0	-10000	0	-10000	0	0
MCF2L	-0.061	0.16	-10000	0	-0.33	111	111
RGS19	0.01	0	-10000	0	-10000	0	0
CDC42	0.01	0	-10000	0	-10000	0	0
RAS family/GTP	-0.009	0.064	-10000	0	-10000	0	0
Rac1/GDP	-0.019	0.075	-10000	0	-0.22	7	7
NGF (dimer)/TRKA/GRIT	-0.035	0.098	-10000	0	-0.31	53	53
neuron projection morphogenesis	-0.002	0.08	-10000	0	-0.45	2	2
NGF (dimer)/TRKA/NEDD4-2	-0.034	0.096	-10000	0	-0.3	53	53
MAP2K1	0.031	0.012	-10000	0	-10000	0	0
NGFR	-0.007	0.091	-10000	0	-0.51	15	15
NGF (dimer)/TRKA/GIPC/GAIP	0.003	0.072	-10000	0	-0.36	1	1
RAS family/GTP/PI3K	0.024	0.012	-10000	0	-0.23	1	1
FRS2 family/SHP2/GRB2/SOS1	-0.001	0.016	-10000	0	-10000	0	0
NRAS	0.01	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
PRKCI	0.01	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCZ	0.007	0.041	-10000	0	-0.5	3	3
MAPKKK cascade	-0.087	0.16	-10000	0	-0.66	33	33
RASA1	0.01	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.015	0.072	-10000	0	-0.35	20	20
SQSTM1	0.009	0.024	-10000	0	-0.51	1	1
BDNF (dimer)/TRKB/GIPC	-0.23	0.19	-10000	0	-0.52	94	94
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.03	0.082	-10000	0	-0.49	2	2
MATK	-0.013	0.11	-10000	0	-0.5	21	21
NEDD4L	0.01	0	-10000	0	-10000	0	0
RAS family/GDP	-0.026	0.048	-10000	0	-0.23	1	1
NGF (dimer)/TRKA	-0.029	0.076	-10000	0	-0.25	39	39
Rac1/GTP	-0.086	0.098	-10000	0	-0.3	45	45
FRS2 family/SHP2/CRK family	-0.001	0.016	-10000	0	-10000	0	0

×

Aurora A 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
Aurora A/GADD45A	-0.012	0.069	-9999	-0.3	2	2
BIRC5	-0.3	0.26	-9999	-0.51	273	273
NFKBIA	-0.009	0.067	-9999	-10000	0	0
CPEB1	-0.064	0.18	-9999	-0.5	67	67
AKT1	-0.009	0.067	-9999	-10000	0	0
NDEL1	0.01	0	-9999	-10000	0	0
Aurora A/BRCA1	-0.017	0.062	-9999	-0.41	2	2
NDEL1/TACC3	-0.013	0.057	-9999	-0.38	2	2
GADD45A	0.008	0.034	-9999	-0.51	2	2
GSK3B	0.011	0.003	-9999	-10000	0	0
PAK1/Aurora A	-0.01	0.066	-9999	-10000	0	0
MDM2	0.008	0.034	-9999	-0.51	2	2
JUB	0.008	0.033	-9999	-0.5	2	2
TPX2	-0.2	0.19	-9999	-0.37	260	260
TP53	0.002	0.044	-9999	-0.18	1	1
DLG7	-0.017	0.067	-9999	-10000	0	0
AURKAIP1	0.009	0.024	-9999	-0.5	1	1
ARHGEF7	0.01	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	-0.013	0.061	-9999	-0.4	2	2
G2/M transition of mitotic cell cycle	-0.017	0.061	-9999	-0.41	2	2
AURKA	-0.019	0.082	-9999	-10000	0	0
AURKB	-0.057	0.054	-9999	-0.13	87	87
CDC25B	-0.012	0.053	-9999	-0.22	1	1
G2/M transition checkpoint	-0.017	0.06	-9999	-0.33	2	2
mRNA polyadenylation	-0.056	0.12	-9999	-0.31	67	67
Aurora A/CPEB	-0.056	0.12	-9999	-0.31	67	67
Aurora A/TACC1/TRAP/chTOG	-0.019	0.075	-9999	-0.37	6	6
BRCA1	0.008	0.034	-9999	-0.51	2	2
centrosome duplication	-0.01	0.066	-9999	-10000	0	0
regulation of centrosome cycle	-0.013	0.056	-9999	-0.38	2	2
spindle assembly	-0.019	0.074	-9999	-0.36	6	6
TDRD7	0.01	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.16	0.15	-9999	-0.37	90	90
CENPA	-0.053	0.052	-9999	-0.14	87	87
Aurora A/PP2A	-0.01	0.066	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.004	0.05	-9999	-10000	0	0
negative regulation of DNA binding	0.002	0.044	-9999	-0.18	1	1
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0	0	-9999	-10000	0	0
RASA1	0.01	0	-9999	-10000	0	0
Ajuba/Aurora A	-0.017	0.06	-9999	-0.33	2	2
mitotic prometaphase	0.015	0.015	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.019	0.082	-9999	-10000	0	0
TACC1	-0.012	0.1	-9999	-0.5	20	20
TACC3	0.008	0.034	-9999	-0.51	2	2
Aurora A/Antizyme1	-0.012	0.057	-9999	-0.26	1	1
Aurora A/RasGAP	-0.01	0.066	-9999	-10000	0	0
OAZ1	0.01	0	-9999	-10000	0	0
RAN	0.009	0.024	-9999	-0.51	1	1
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.011	0.003	-9999	-10000	0	0
GIT1	0.01	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0	0	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.2	0.19	-9999	-0.36	260	260
PPP2R5D	0.01	0	-9999	-10000	0	0
Aurora A/TPX2	-0.16	0.18	-9999	-0.31	260	260
PAK1	0.01	0	-9999	-10000	0	0
CKAP5	0.01	0	-9999	-10000	0	0

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.12	0.39	-10000	0	-1.1	40	40
IL23A	-0.15	0.42	-10000	0	-1.2	36	36
NF kappa B1 p50/RelA/I kappa B alpha	-0.2	0.34	-10000	0	-1.1	42	42
positive regulation of T cell mediated cytotoxicity	-0.15	0.44	-10000	0	-1.2	42	42
ITGA3	-0.13	0.4	-10000	0	-1.2	38	38
IL17F	-0.068	0.27	-10000	0	-0.73	32	32
IL12B	0.011	0.061	-10000	0	-0.52	5	5
STAT1 (dimer)	-0.14	0.42	-10000	0	-1.2	42	42
CD4	-0.12	0.4	-10000	0	-1.1	38	38
IL23	-0.15	0.4	-10000	0	-1.2	37	37
IL23R	0	0.083	-10000	0	-10000	0	0
IL1B	-0.16	0.45	-10000	0	-1.3	43	43
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.12	0.38	-10000	0	-1.1	38	38
TYK2	0.01	0.019	-10000	0	-10000	0	0
STAT4	0.01	0	-10000	0	-10000	0	0
STAT3	0.01	0.001	-10000	0	-10000	0	0
IL18RAP	-0.01	0.098	-10000	0	-0.5	18	18
IL12RB1	-0.006	0.097	-10000	0	-0.53	15	15
PIK3CA	0.01	0	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	-0.002	0.075	-10000	0	-0.39	15	15
IL23R/JAK2	0.003	0.1	-10000	0	-10000	0	0
positive regulation of chronic inflammatory response	-0.15	0.44	-10000	0	-1.2	42	42
natural killer cell activation	0.001	0.007	0.036	1	-10000	0	1
JAK2	0.016	0.034	-10000	0	-0.5	1	1
PIK3R1	0.009	0.024	-10000	0	-0.5	1	1
NFKB1	0.009	0.003	-10000	0	-10000	0	0
RELA	0.009	0.003	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.14	0.38	-10000	0	-1.1	37	37
ALOX12B	-0.14	0.4	-10000	0	-1.1	42	42
CXCL1	-0.14	0.43	-10000	0	-1.2	44	44
T cell proliferation	-0.15	0.44	-10000	0	-1.2	42	42
NFKBIA	0.009	0.003	-10000	0	-10000	0	0
IL17A	-0.048	0.23	-10000	0	-0.58	23	23
PI3K	-0.2	0.35	-10000	0	-1.1	42	42
IFNG	-0.006	0.033	-10000	0	-0.12	11	11
STAT3 (dimer)	-0.19	0.33	-10000	0	-1.1	41	41
IL18R1	-0.012	0.1	-10000	0	-0.5	20	20
IL23/IL23R/JAK2/TYK2/SOCS3	-0.058	0.25	-10000	0	-0.68	27	27
IL18/IL18R	-0.017	0.11	-10000	0	-0.36	38	38
macrophage activation	-0.013	0.016	-10000	0	-0.044	33	33
TNF	-0.15	0.44	-10000	0	-1.3	42	42
STAT3/STAT4	-0.2	0.35	-10000	0	-1.1	42	42
STAT4 (dimer)	-0.14	0.42	-10000	0	-1.2	41	41
IL18	0	0.07	-10000	0	-0.5	9	9
IL19	-0.13	0.39	-10000	0	-1.1	38	38
STAT5A (dimer)	-0.14	0.42	-10000	0	-1.2	41	41
STAT1	0.01	0	-10000	0	-10000	0	0
SOCS3	0.005	0.047	-10000	0	-0.5	4	4
CXCL9	-0.14	0.41	-10000	0	-1.1	45	45
MPO	-0.13	0.41	-10000	0	-1.1	44	44
positive regulation of humoral immune response	-0.15	0.44	-10000	0	-1.2	42	42
IL23/IL23R/JAK2/TYK2	-0.16	0.48	-10000	0	-1.3	42	42
IL6	-0.28	0.58	-10000	0	-1.2	115	115
STAT5A	0.009	0.024	-10000	0	-0.5	1	1
IL2	0.007	0.009	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0.001	0.007	0.036	1	-10000	0	1
CD3E	-0.12	0.39	-10000	0	-1.1	39	39
keratinocyte proliferation	-0.15	0.44	-10000	0	-1.2	42	42
NOS2	-0.18	0.47	-10000	0	-1.2	70	70

×

Presenilin action in Notch and Wnt signaling

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
Delta 1/NOTCH/NOTCH(cleaved)	-0.01	0.063	-10000	0	-0.54	5	5
HDAC1	0.002	0.007	-10000	0	-10000	0	0
AES	0.009	0.002	-10000	0	-10000	0	0
FBXW11	0.01	0	-10000	0	-10000	0	0
DTX1	0.006	0.042	-10000	0	-0.51	3	3
LRP6/FZD1	0	0	-10000	0	-10000	0	0
TLE1	0.009	0.002	-10000	0	-10000	0	0
AP1	-0.033	0.12	-10000	0	-0.29	78	78
NCSTN	0.01	0	-10000	0	-10000	0	0
ADAM10	0.01	0	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.011	0.056	-10000	0	-0.36	1	1
NICD/RBPSUH	-0.006	0.056	-10000	0	-0.54	5	5
WIF1	-0.34	0.24	-10000	0	-0.5	325	325
NOTCH1	-0.006	0.059	-10000	0	-0.57	5	5
PSENEN	0.009	0.024	-10000	0	-0.52	1	1
KREMEN2	-0.12	0.23	-10000	0	-0.51	119	119
DKK1	-0.13	0.23	-10000	0	-0.51	123	123
beta catenin/beta TrCP1	0.019	0.053	-10000	0	-10000	0	0
APH1B	0.008	0.033	-10000	0	-0.5	2	2
APH1A	0.01	0	-10000	0	-10000	0	0
AXIN1	-0.005	0.026	-10000	0	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	-0.013	0.063	0.28	1	-10000	0	1
PSEN1	0.01	0	-10000	0	-10000	0	0
FOS	-0.024	0.13	-10000	0	-0.5	31	31
JUN	0.005	0.047	-10000	0	-0.5	4	4
MAP3K7	0.009	0.002	-10000	0	-10000	0	0
CTNNB1	0.014	0.056	-10000	0	-10000	0	0
MAPK3	0.01	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.13	0.19	-10000	0	-0.36	175	175
HNF1A	-0.094	0.21	-10000	0	-0.51	92	92
CTBP1	0.009	0.002	-10000	0	-10000	0	0
MYC	0.015	0.088	-10000	0	-1.3	2	2
NKD1	-0.054	0.17	-10000	0	-0.5	58	58
FZD1	0.01	0	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.008	0.059	-10000	0	-0.54	5	5
apoptosis	-0.033	0.12	-10000	0	-0.29	78	78
Delta 1/NOTCHprecursor	-0.01	0.063	-10000	0	-0.54	5	5
DLL1	0.001	0.066	-10000	0	-0.5	8	8
PPARD	0.02	0.013	-10000	0	-10000	0	0
Gamma Secretase	-0.002	0.019	-10000	0	-10000	0	0
APC	-0.005	0.026	-10000	0	-10000	0	0
DVL1	-0.032	0.033	-10000	0	-0.43	2	2
CSNK2A1	0.01	0.001	-10000	0	-10000	0	0
MAP3K7IP1	-0.001	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.15	0.19	-10000	0	-0.35	205	205
LRP6	0.01	0	-10000	0	-10000	0	0
CSNK1A1	0.01	0.001	-10000	0	-10000	0	0
NLK	0.011	0.005	-10000	0	-10000	0	0
CCND1	0.005	0.15	-10000	0	-1.3	6	6
WNT1	0	0.068	-10000	0	-0.51	8	8
Axin1/APC/beta catenin	0.012	0.041	-10000	0	-0.28	1	1
DKK2	-0.092	0.2	-10000	0	-0.5	93	93
NOTCH1 precursor/DVL1	-0.017	0.057	-10000	0	-0.49	6	6
GSK3B	0.01	0	-10000	0	-10000	0	0
FRAT1	0.009	0.001	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.008	0.059	-10000	0	-0.54	5	5
PPP2R5D	0.016	0.086	0.24	58	-0.2	1	59
MAPK1	0.01	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.18	0.12	-10000	0	-0.3	37	37
RBPJ	0.01	0	-10000	0	-10000	0	0
CREBBP	0.013	0.002	-10000	0	-10000	0	0

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	-0.066	0.19	-10000	0	-0.52	70	70
NFATC2	0.004	0.17	-10000	0	-0.73	14	14
NFATC3	-0.01	0.08	-10000	0	-0.3	7	7
CD40LG	-0.074	0.36	-10000	0	-0.94	50	50
ITCH	-0.009	0.098	-10000	0	-10000	0	0
CBLB	-0.009	0.098	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.12	0.23	-10000	0	-0.97	19	19
JUNB	0.007	0.041	-10000	0	-0.5	3	3
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.049	0.1	-10000	0	-10000	0	0
T cell anergy	-0.057	0.16	-10000	0	-0.39	68	68
TLE4	0.021	0.15	-10000	0	-0.89	8	8
Jun/NFAT1-c-4/p21SNFT	-0.12	0.3	-10000	0	-0.92	47	47
AP-1/NFAT1-c-4	-0.086	0.4	-10000	0	-1.1	47	47
IKZF1	0.021	0.16	-10000	0	-0.89	9	9
T-helper 2 cell differentiation	0.005	0.19	-10000	0	-0.86	11	11
AP-1/NFAT1	-0.052	0.13	-10000	0	-0.55	18	18
CALM1	-0.01	0.065	-10000	0	-10000	0	0
EGR2	-0.048	0.38	-10000	0	-1.4	25	25
EGR3	-0.093	0.47	-10000	0	-1.4	52	52
NFAT1/FOXP3	-0.044	0.18	-10000	0	-0.52	25	25
EGR1	-0.022	0.12	-10000	0	-0.5	30	30
JUN	0.003	0.05	-10000	0	-0.5	4	4
EGR4	-0.043	0.16	-10000	0	-0.51	47	47
mol:Ca2+	-0.021	0.069	-10000	0	-10000	0	0
GBP3	0.006	0.19	-10000	0	-0.75	22	22
FOSL1	-0.017	0.12	-10000	0	-0.51	24	24
NFAT1-c-4/MAF/IRF4	-0.11	0.3	-10000	0	-0.91	44	44
DGKA	0.025	0.13	-10000	0	-0.78	6	6
CREM	0.009	0	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.14	0.33	-10000	0	-0.94	54	54
CTLA4	-0.027	0.16	-10000	0	-0.64	13	13
NFAT1-c-4 (dimer)/EGR1	-0.12	0.33	-10000	0	-0.98	51	51
NFAT1-c-4 (dimer)/EGR4	-0.13	0.31	-10000	0	-0.9	54	54
FOS	-0.027	0.13	-10000	0	-0.52	31	31
IFNG	-0.092	0.24	-10000	0	-0.96	23	23
T cell activation	0.01	0.2	-10000	0	-0.8	11	11
MAF	0.009	0.024	-10000	0	-0.5	1	1
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.03	0.28	0.76	44	-10000	0	44
TNF	-0.073	0.34	-10000	0	-0.92	49	49
FASLG	-0.11	0.48	-10000	0	-1.3	59	59
TBX21	-0.014	0.11	-10000	0	-0.5	21	21
BATF3	0.009	0.024	-10000	0	-0.51	1	1
PRKCQ	-0.065	0.18	-10000	0	-0.5	71	71
PTPN1	0.026	0.13	-10000	0	-0.78	6	6
NFAT1-c-4/ICER1	-0.11	0.3	-10000	0	-0.87	55	55
GATA3	0.007	0.041	-10000	0	-0.5	3	3
T-helper 1 cell differentiation	-0.053	0.25	-10000	0	-0.93	23	23
IL2RA	-0.12	0.22	-10000	0	-0.88	20	20
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	0.026	0.13	-10000	0	-0.78	6	6
E2F1	0.006	0.064	-10000	0	-0.51	7	7
PPARG	-0.053	0.17	-10000	0	-0.5	58	58
SLC3A2	0.026	0.13	-10000	0	-0.72	7	7
IRF4	-0.007	0.092	-10000	0	-0.51	15	15
PTGS2	-0.091	0.37	-10000	0	-0.97	52	52
CSF2	-0.083	0.36	-10000	0	-0.94	52	52
JunB/Fra1/NFAT1-c-4	-0.12	0.3	-10000	0	-0.9	47	47
IL4	0.004	0.2	-10000	0	-0.91	11	11
IL5	-0.068	0.34	-10000	0	-0.91	46	46
IL2	0.009	0.2	-10000	0	-0.81	11	11
IL3	-0.026	0.046	-10000	0	-10000	0	0
RNF128	-0.076	0.24	-10000	0	-0.57	86	86
NFATC1	-0.031	0.28	-10000	0	-0.76	44	44
CDK4	0.008	0.17	0.57	17	-10000	0	17
PTPRK	0.026	0.13	-10000	0	-0.78	6	6
IL8	-0.075	0.35	-10000	0	-0.91	47	47
POU2F1	0.01	0.001	-10000	0	-10000	0	0

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.14	0.22	-10000	0	-0.64	18	18
CRP	-0.15	0.23	-10000	0	-0.68	15	15
cell cycle arrest	-0.16	0.25	-10000	0	-0.58	71	71
TIMP1	-0.11	0.2	-10000	0	-0.61	13	13
IL6ST	-0.011	0.095	-10000	0	-0.5	17	17
Rac1/GDP	-0.067	0.14	-10000	0	-0.43	23	23
AP1	0.001	0.091	-10000	0	-0.59	3	3
GAB2	0.008	0.047	-10000	0	-0.5	4	4
TNFSF11	-0.19	0.25	-10000	0	-0.65	39	39
HSP90B1	-0.004	0.044	-10000	0	-10000	0	0
GAB1	0.01	0.024	-10000	0	-0.5	1	1
MAPK14	-0.046	0.14	-10000	0	-0.52	17	17
AKT1	0.037	0.031	-10000	0	-10000	0	0
FOXO1	0.042	0.029	-10000	0	-10000	0	0
MAP2K6	-0.063	0.14	-10000	0	-0.42	27	27
mol:GTP	-0.002	0.002	-10000	0	-10000	0	0
MAP2K4	-0.08	0.16	-10000	0	-0.47	20	20
MITF	-0.069	0.14	-10000	0	-0.34	63	63
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.01	0	-10000	0	-10000	0	0
A2M	-0.082	0.35	-10000	0	-1.3	36	36
CEBPB	0.015	0.003	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	-0.008	0.081	-10000	0	-0.56	3	3
STAT3	-0.17	0.26	-10000	0	-0.6	71	71
STAT1	-0.002	0.012	-10000	0	-10000	0	0
CEBPD	-0.14	0.23	-10000	0	-0.77	13	13
PIK3CA	0.011	0	-10000	0	-10000	0	0
PI3K	0.013	0.018	-10000	0	-0.35	1	1
JUN	0.005	0.047	-10000	0	-0.5	4	4
PIAS3/MITF	-0.059	0.14	-10000	0	-0.46	17	17
MAPK11	-0.047	0.14	-10000	0	-0.52	18	18
STAT3 (dimer)/FOXO1	-0.11	0.24	-10000	0	-0.65	30	30
GRB2/SOS1/GAB family	-0.057	0.12	0.18	2	-0.43	20	22
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.064	0.15	-10000	0	-0.35	71	71
GRB2	0.011	0.004	-10000	0	-10000	0	0
JAK2	0.009	0.024	-10000	0	-0.5	1	1
LBP	-0.12	0.2	-10000	0	-0.56	20	20
PIK3R1	0.01	0.024	-10000	0	-0.5	1	1
JAK1	0.009	0.005	-10000	0	-10000	0	0
MYC	-0.14	0.23	-10000	0	-0.73	13	13
FGG	-0.33	0.46	-10000	0	-0.99	141	141
macrophage differentiation	-0.16	0.25	-10000	0	-0.58	71	71
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.071	0.12	-10000	0	-0.39	19	19
JUNB	-0.14	0.22	-10000	0	-0.7	16	16
FOS	-0.024	0.13	-10000	0	-0.5	31	31
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.076	0.14	-10000	0	-0.34	71	71
STAT1/PIAS1	-0.078	0.14	-10000	0	-0.35	57	57
GRB2/SOS1/GAB family/SHP2/PI3K	0.019	0.036	-10000	0	-10000	0	0
STAT3 (dimer)	-0.17	0.26	-10000	0	-0.6	71	71
PRKCD	-0.094	0.18	-10000	0	-0.56	15	15
IL6R	-0.003	0.078	-10000	0	-0.51	11	11
SOCS3	-0.035	0.16	-10000	0	-0.76	10	10
gp130 (dimer)/JAK1/JAK1/LMO4	0.001	0.062	-10000	0	-0.29	18	18
Rac1/GTP	-0.08	0.15	-10000	0	-0.44	24	24
HCK	-0.011	0.1	-10000	0	-0.5	19	19
MAPKKK cascade	0.01	0.079	-10000	0	-0.59	4	4
bone resorption	-0.18	0.24	-10000	0	-0.62	39	39
IRF1	-0.14	0.22	-10000	0	-0.66	15	15
mol:GDP	-0.07	0.14	-10000	0	-0.35	61	61
SOS1	0.012	0.006	-10000	0	-10000	0	0
VAV1	-0.071	0.15	-10000	0	-0.36	61	61
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.041	0.14	-10000	0	-0.48	22	22
PTPN11	-0.001	0.01	-10000	0	-10000	0	0
IL6/IL6RA	-0.083	0.16	-10000	0	-0.36	115	115
gp130 (dimer)/TYK2/TYK2/LMO4	-0.001	0.06	-10000	0	-0.29	18	18
gp130 (dimer)/JAK2/JAK2/LMO4	-0.001	0.062	-10000	0	-0.29	19	19
IL6	-0.11	0.21	-10000	0	-0.5	106	106
PIAS3	0.01	0	-10000	0	-10000	0	0
PTPRE	0.012	0.035	-10000	0	-0.49	2	2
PIAS1	0.01	0	-10000	0	-10000	0	0
RAC1	0.009	0.001	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.066	0.13	-10000	0	-0.3	88	88
LMO4	0.006	0.025	-10000	0	-0.5	1	1
STAT3 (dimer)/PIAS3	-0.19	0.21	-10000	0	-0.58	59	59
MCL1	0.042	0.028	-10000	0	-10000	0	0

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.13	0.23	-9999	-0.5	130	130
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.01	0	-9999	-10000	0	0
TCEB1	0.008	0.034	-9999	-0.51	2	2
HIF1A/p53	0.005	0.035	-9999	-10000	0	0
HIF1A	-0.001	0.036	-9999	-10000	0	0
COPS5	0.01	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	-0.001	0.016	-9999	-10000	0	0
FIH (dimer)	0.01	0	-9999	-10000	0	0
CDKN2A	-0.15	0.24	-9999	-0.51	142	142
ARNT/IPAS	-0.098	0.16	-9999	-0.35	130	130
HIF1AN	0.01	0	-9999	-10000	0	0
GNB2L1	0.01	0	-9999	-10000	0	0
HIF1A/ARNT	0.005	0.035	-9999	-10000	0	0
CUL2	0.01	0	-9999	-10000	0	0
OS9	0.01	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	-0.001	0.02	-9999	-0.3	2	2
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.005	0.035	-9999	-10000	0	0
PHD1-3/OS9	-0.068	0.12	-9999	-0.27	118	118
HIF1A/RACK1/Elongin B/Elongin C	-0.011	0.023	-9999	-0.28	1	1
VHL	0.01	0	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
HIF1A/JAB1	0.005	0.035	-9999	-10000	0	0
EGLN3	-0.12	0.23	-9999	-0.51	119	119
EGLN2	0.01	0	-9999	-10000	0	0
EGLN1	0.01	0	-9999	-10000	0	0
TP53	0.01	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.025	0.01	-9999	-10000	0	0
ARNT	0.01	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.01	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.072	0.12	-9999	-0.25	142	142

×

PDGFR-alpha signaling pathway

Figure S42. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S42. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.004	0.048	-9999	-0.5	4	4
PDGF/PDGFRA/CRKL	-0.003	0.031	-9999	-0.34	4	4
positive regulation of JUN kinase activity	-0.002	0.022	-9999	-10000	0	0
CRKL	0.01	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.083	0.15	-9999	-0.36	107	107
AP1	-0.061	0.22	-9999	-0.87	31	31
mol:IP3	0.014	0.038	-9999	-0.35	4	4
PLCG1	0.014	0.038	-9999	-0.35	4	4
PDGF/PDGFRA/alphaV Integrin	-0.003	0.031	-9999	-0.34	4	4
RAPGEF1	0.01	0	-9999	-10000	0	0
CRK	0.01	0	-9999	-10000	0	0
mol:Ca2+	0.014	0.037	-9999	-0.35	4	4
CAV3	-0.11	0.21	-9999	-0.5	103	103
CAV1	-0.31	0.25	-9999	-0.5	295	295
SHC/Grb2/SOS1	-0.002	0.022	-9999	-10000	0	0
PDGF/PDGFRA/Shf	-0.005	0.04	-9999	-0.35	6	6
FOS	-0.026	0.22	-9999	-0.86	31	31
JUN	-0.007	0.036	-9999	-0.36	4	4
oligodendrocyte development	-0.003	0.031	-9999	-0.34	4	4
GRB2	0.01	0	-9999	-10000	0	0
PIK3R1	0.009	0.024	-9999	-0.5	1	1
mol:DAG	0.014	0.038	-9999	-0.35	4	4
PDGF/PDGFRA	0.004	0.048	-9999	-0.5	4	4
actin cytoskeleton reorganization	-0.004	0.036	-9999	-0.35	5	5
SRF	0.018	0.006	-9999	-10000	0	0
SHC1	0.01	0	-9999	-10000	0	0
PI3K	-0.003	0.029	-9999	-0.28	5	5
PDGF/PDGFRA/Crk/C3G	-0.002	0.026	-9999	-0.28	4	4
JAK1	0.015	0.034	-9999	-0.34	4	4
ELK1/SRF	0.027	0.028	-9999	-10000	0	0
SHB	0.009	0.024	-9999	-0.5	1	1
SHF	0.008	0.034	-9999	-0.51	2	2
CSNK2A1	0.004	0.014	-9999	-10000	0	0
GO:0007205	0.014	0.04	-9999	-0.38	4	4
SOS1	0.01	0	-9999	-10000	0	0
Ras protein signal transduction	-0.002	0.022	-9999	-10000	0	0
PDGF/PDGFRA/SHB	-0.004	0.036	-9999	-0.35	5	5
PDGF/PDGFRA/Caveolin-1	-0.23	0.18	-9999	-0.36	296	296
ITGAV	0.01	0	-9999	-10000	0	0
ELK1	0.018	0.04	-9999	-0.32	4	4
PIK3CA	0.01	0	-9999	-10000	0	0
PDGF/PDGFRA/Crk	-0.003	0.031	-9999	-0.34	4	4
JAK-STAT cascade	0.015	0.033	-9999	-0.34	4	4
cell proliferation	-0.005	0.039	-9999	-0.35	6	6

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.032	0.12	-9999	-0.41	20	20
FZD6	0.009	0.024	-9999	-0.5	1	1
WNT6	-0.021	0.12	-9999	-0.51	27	27
WNT4	-0.022	0.12	-9999	-0.5	29	29
FZD3	0.009	0.024	-9999	-0.51	1	1
WNT5A	0.004	0.052	-9999	-0.5	5	5
WNT11	-0.061	0.18	-9999	-0.5	65	65

×

Class IB PI3K non-lipid kinase events

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
cAMP biosynthetic process	0.013	0.1	0.5	21	-10000	0	21
PI3K Class IB/PDE3B	-0.013	0.11	-10000	0	-0.5	21	21
PDE3B	-0.013	0.11	-10000	0	-0.5	21	21

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0.038	0.11	0.36	49	-10000	0	49
KIRREL	-0.008	0.088	-10000	0	-0.5	14	14
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.038	0.11	-10000	0	-0.36	49	49
PLCG1	0.01	0	-10000	0	-10000	0	0
ARRB2	0.01	0	-10000	0	-10000	0	0
WASL	0.01	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.026	0.077	-10000	0	-0.26	13	13
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.007	0.056	-10000	0	-0.24	13	13
FYN	-0.01	0.074	-10000	0	-0.24	14	14
mol:Ca2+	-0.026	0.076	-10000	0	-0.25	46	46
mol:DAG	-0.026	0.076	-10000	0	-0.25	46	46
NPHS2	-0.002	0.015	-10000	0	-10000	0	0
mol:IP3	-0.026	0.076	-10000	0	-0.25	46	46
regulation of endocytosis	-0.022	0.063	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/Cholesterol	-0.027	0.079	-10000	0	-0.26	49	49
establishment of cell polarity	-0.038	0.11	-10000	0	-0.36	49	49
Nephrin/NEPH1/podocin/NCK1-2	-0.023	0.068	-10000	0	-10000	0	0
Nephrin/NEPH1/beta Arrestin2	-0.022	0.064	-10000	0	-10000	0	0
NPHS1	-0.032	0.14	-10000	0	-0.51	35	35
Nephrin/NEPH1/podocin	-0.024	0.069	-10000	0	-0.25	14	14
TJP1	0.01	0	-10000	0	-10000	0	0
NCK1	0.01	0	-10000	0	-10000	0	0
NCK2	0.01	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.026	0.077	-10000	0	-0.25	46	46
CD2AP	0.01	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.026	0.077	-10000	0	-0.26	13	13
GRB2	0.01	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.027	0.1	-10000	0	-0.25	78	78
cytoskeleton organization	0.009	0.065	-10000	0	-10000	0	0
Nephrin/NEPH1	-0.026	0.076	-10000	0	-0.25	49	49
Nephrin/NEPH1/ZO-1	-0.029	0.084	-10000	0	-0.28	49	49

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.074	0.14	-10000	0	-0.41	40	40
epithelial cell differentiation	-0.077	0.12	-10000	0	-0.45	17	17
ITCH	0.023	0.018	-10000	0	-10000	0	0
WWP1	-0.02	0.068	-10000	0	-10000	0	0
FYN	0.009	0.024	-10000	0	-0.5	1	1
EGFR	-0.006	0.088	-10000	0	-0.51	14	14
PRL	-0.011	0.085	-10000	0	-0.51	13	13
neuron projection morphogenesis	-0.025	0.11	-10000	0	-0.4	1	1
PTPRZ1	-0.12	0.22	-10000	0	-0.51	114	114
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.065	0.1	-10000	0	-0.44	1	1
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.067	0.14	-10000	0	-0.37	48	48
ADAM17	0.023	0.018	-10000	0	-10000	0	0
ErbB4/ErbB4	-0.034	0.089	-10000	0	-0.38	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.14	0.17	-10000	0	-0.41	81	81
NCOR1	0.01	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.077	0.12	-10000	0	-0.53	2	2
GRIN2B	-0.058	0.13	-10000	0	-0.5	5	5
ErbB4/ErbB2/betacellulin	-0.033	0.062	-10000	0	-10000	0	0
STAT1	0.01	0	-10000	0	-10000	0	0
HBEGF	-0.076	0.19	-10000	0	-0.5	79	79
PRLR	-0.056	0.17	-10000	0	-0.51	59	59
E4ICDs/ETO2	-0.044	0.11	-10000	0	-0.42	18	18
axon guidance	0.003	0.076	-10000	0	-10000	0	0
NEDD4	0.022	0.029	-10000	0	-0.48	1	1
Prolactin receptor/Prolactin receptor/Prolactin	-0.056	0.14	-10000	0	-0.37	70	70
CBFA2T3	-0.025	0.13	-10000	0	-0.5	32	32
ErbB4/ErbB2/HBEGF	-0.069	0.11	-10000	0	-0.48	1	1
MAPK3	-0.032	0.11	-10000	0	-0.41	1	1
STAT1 (dimer)	-0.024	0.074	-10000	0	-10000	0	0
MAPK1	-0.032	0.11	-10000	0	-0.41	1	1
JAK2	0.009	0.024	-10000	0	-0.5	1	1
ErbB4/ErbB2/neuregulin 1 beta	-0.078	0.12	-10000	0	-0.49	2	2
NRG1	-0.051	0.15	-10000	0	-0.35	95	95
NRG3	-0.19	0.25	-10000	0	-0.5	183	183
NRG2	-0.05	0.16	-10000	0	-0.5	54	54
NRG4	-0.037	0.15	-10000	0	-0.51	41	41
heart development	0.003	0.076	-10000	0	-10000	0	0
neural crest cell migration	-0.077	0.12	-10000	0	-0.48	2	2
ERBB2	0.024	0.033	-10000	0	-0.36	3	3
WWOX/E4ICDs	-0.025	0.074	-10000	0	-10000	0	0
SHC1	0.01	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.068	0.11	-10000	0	-0.4	27	27
apoptosis	0.2	0.22	0.55	105	-10000	0	105
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.059	0.13	-10000	0	-0.41	30	30
ErbB4/ErbB2/epiregulin	-0.1	0.13	-10000	0	-0.48	1	1
ErbB4/ErbB4/betacellulin/betacellulin	-0.031	0.091	-10000	0	-0.41	9	9
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.11	0.15	-10000	0	-0.54	21	21
MDM2	-0.023	0.078	-10000	0	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.07	0.11	-10000	0	-0.43	1	1
STAT5A	0.009	0.072	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.083	0.12	-10000	0	-0.55	7	7
DLG4	0.01	0	-10000	0	-10000	0	0
GRB2/SHC	0	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.04	0.055	-10000	0	-10000	0	0
STAT5A (dimer)	-0.082	0.13	-10000	0	-0.5	14	14
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.007	0.069	-10000	0	-10000	0	0
LRIG1	0.008	0.033	-10000	0	-0.5	2	2
EREG	-0.15	0.24	-10000	0	-0.51	146	146
BTC	-0.002	0.077	-10000	0	-0.5	11	11
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0	0.074	-10000	0	-10000	0	0
ERBB4	-0.034	0.089	-10000	0	-0.38	1	1
STAT5B	0.01	0	-10000	0	-10000	0	0
YAP1	-0.001	0.025	-10000	0	-0.53	1	1
GRB2	0.01	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.05	0.087	-10000	0	-10000	0	0
glial cell differentiation	0.04	0.055	-10000	0	-10000	0	0
WWOX	0.01	0	-10000	0	-10000	0	0
cell proliferation	-0.066	0.15	-10000	0	-0.49	20	20

×

Syndecan-3-mediated signaling events

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
CTTN	0.01	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.029	0.073	-9999	-10000	0	0
Syndecan-3/Neurocan	-0.007	0.042	-9999	-0.25	13	13
POMC	-0.014	0.11	-9999	-0.5	22	22
EGFR	-0.006	0.088	-9999	-0.51	14	14
Syndecan-3/EGFR	-0.008	0.041	-9999	-0.24	14	14
AGRP	-0.2	0.25	-9999	-0.5	189	189
NCSTN	0.01	0	-9999	-10000	0	0
PSENEN	0.009	0.024	-9999	-0.51	1	1
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.008	0.033	-9999	-0.5	2	2
APH1A	0.01	0	-9999	-10000	0	0
NCAN	-0.008	0.086	-9999	-0.51	13	13
long-term memory	-0.001	0.011	-9999	-10000	0	0
Syndecan-3/IL8	-0.011	0.051	-9999	-0.25	17	17
PSEN1	0.01	0	-9999	-10000	0	0
Src/Cortactin	0	0	-9999	-10000	0	0
FYN	0.009	0.024	-9999	-0.5	1	1
limb bud formation	0	0.004	-9999	-10000	0	0
MC4R	-0.03	0.13	-9999	-0.51	33	33
SRC	0.01	0	-9999	-10000	0	0
PTN	-0.06	0.18	-9999	-0.5	64	64
FGFR/FGF/Syndecan-3	0	0.004	-9999	-10000	0	0
neuron projection morphogenesis	-0.034	0.08	-9999	-0.44	3	3
Syndecan-3/AgRP	-0.097	0.12	-9999	-0.24	189	189
Syndecan-3/AgRP/MC4R	-0.11	0.13	-9999	-0.45	14	14
Fyn/Cortactin	-0.001	0.016	-9999	-0.35	1	1
SDC3	0	0.004	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.011	0.05	-9999	-0.24	17	17
IL8	-0.014	0.11	-9999	-0.51	21	21
Syndecan-3/Fyn/Cortactin	-0.001	0.011	-9999	-10000	0	0
Syndecan-3/CASK	0	0.004	-9999	-10000	0	0
alpha-MSH/MC4R	-0.042	0.12	-9999	-0.38	52	52
Gamma Secretase	-0.002	0.019	-9999	-10000	0	0

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.009	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.037	0.093	-10000	0	-0.27	64	64
regulation of S phase of mitotic cell cycle	-0.01	0.087	-10000	0	-0.25	12	12
GNAO1	0.004	0.053	-10000	0	-0.51	5	5
HRAS	0.01	0.001	-10000	0	-10000	0	0
SHBG/T-DHT	-0.001	0.021	-10000	0	-0.32	2	2
PELP1	0.01	0.001	-10000	0	-10000	0	0
AKT1	0.009	0	-10000	0	-10000	0	0
MAP2K1	0	0.091	-10000	0	-0.32	12	12
T-DHT/AR	-0.049	0.12	-10000	0	-0.36	63	63
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.002	-10000	0	-0.006	31	31
GNAI2	0.01	0	-10000	0	-10000	0	0
GNAI3	0.01	0	-10000	0	-10000	0	0
GNAI1	0.008	0.033	-10000	0	-0.5	2	2
mol:GDP	-0.053	0.14	-10000	0	-0.4	61	61
cell proliferation	-0.002	0.14	-10000	0	-0.43	31	31
PIK3CA	0.01	0	-10000	0	-10000	0	0
FOS	-0.022	0.21	-10000	0	-0.79	31	31
mol:Ca2+	-0.01	0.022	-10000	0	-0.064	49	49
MAPK3	0	0.11	-10000	0	-0.45	12	12
MAPK1	0.004	0.068	-10000	0	-0.26	12	12
PIK3R1	0.009	0.024	-10000	0	-0.5	1	1
mol:IP3	0	0.001	-10000	0	-0.004	31	31
cAMP biosynthetic process	0.008	0.028	-10000	0	-0.3	2	2
GNG2	0.008	0.033	-10000	0	-0.5	2	2
potassium channel inhibitor activity	0	0.001	-10000	0	-0.004	31	31
HRAS/GTP	-0.034	0.082	-10000	0	-0.29	12	12
actin cytoskeleton reorganization	0	0.011	-10000	0	-10000	0	0
SRC	0.01	0.001	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.004	31	31
PI3K	-0.001	0.014	-10000	0	-0.3	1	1
apoptosis	0.002	0.13	0.43	31	-10000	0	31
T-DHT/AR/PELP1	-0.04	0.1	-10000	0	-0.3	63	63
HRAS/GDP	-0.049	0.13	-10000	0	-0.37	61	61
CREB1	-0.004	0.14	-10000	0	-0.46	31	31
RAC1-CDC42/GTP	0	0.011	-10000	0	-10000	0	0
AR	-0.059	0.18	-10000	0	-0.5	63	63
GNB1	0.01	0	-10000	0	-10000	0	0
RAF1	-0.005	0.091	-10000	0	-0.3	12	12
RAC1-CDC42/GDP	-0.046	0.12	-10000	0	-0.35	61	61
T-DHT/AR/PELP1/Src	-0.036	0.092	-10000	0	-0.27	63	63
MAP2K2	0	0.091	-10000	0	-0.32	12	12
T-DHT/AR/PELP1/Src/PI3K	-0.01	0.087	-10000	0	-0.26	12	12
GNAZ	-0.035	0.14	-10000	0	-0.5	41	41
SHBG	0.007	0.034	-10000	0	-0.51	2	2
Gi family/GNB1/GNG2/GDP	0.003	0.08	-10000	0	-0.32	8	8
mol:T-DHT	0	0.001	-10000	0	-0.003	19	19
RAC1	0.01	0	-10000	0	-10000	0	0
GNRH1	0.006	0.034	-10000	0	-0.36	4	4
Gi family/GTP	-0.036	0.083	-10000	0	-0.34	17	17
CDC42	0.01	0	-10000	0	-10000	0	0

×

Regulation of Androgen receptor activity

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.018	0.001	-9999	-10000	0	0
SMARCC1	0.003	0.007	-9999	-10000	0	0
REL	0.01	0.001	-9999	-10000	0	0
HDAC7	0.022	0.092	-9999	-0.41	5	5
JUN	0.005	0.047	-9999	-0.5	4	4
EP300	0.01	0	-9999	-10000	0	0
KAT2B	0.01	0	-9999	-10000	0	0
KAT5	0.01	0	-9999	-10000	0	0
MAPK14	0.004	0.075	-9999	-0.37	18	18
FOXO1	0.01	0	-9999	-10000	0	0
T-DHT/AR	0.019	0.097	-9999	-0.42	6	6
MAP2K6	-0.01	0.1	-9999	-0.51	18	18
BRM/BAF57	-0.003	0.033	-9999	-0.35	4	4
MAP2K4	0.01	0.004	-9999	-10000	0	0
SMARCA2	0.005	0.047	-9999	-0.5	4	4
PDE9A	-0.047	0.17	-9999	-1.2	8	8
NCOA2	0.005	0.047	-9999	-0.5	4	4
CEBPA	-0.016	0.11	-9999	-0.5	24	24
EHMT2	0.01	0.001	-9999	-10000	0	0
cell proliferation	0.018	0.13	-9999	-0.45	19	19
NR0B1	-0.099	0.21	-9999	-0.51	93	93
EGR1	-0.023	0.12	-9999	-0.5	30	30
RXRs/9cRA	-0.14	0.13	-9999	-0.26	242	242
AR/RACK1/Src	-0.002	0.067	-9999	-0.33	5	5
AR/GR	-0.007	0.097	-9999	-0.3	25	25
GNB2L1	0.01	0.001	-9999	-10000	0	0
PKN1	0.01	0	-9999	-10000	0	0
RCHY1	0.01	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0.002	-9999	-10000	0	0
MAPK8	0.018	0.009	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.003	0.07	-9999	-0.38	3	3
SRC	0.022	0.058	-9999	-0.29	5	5
NR3C1	0.01	0	-9999	-10000	0	0
KLK3	-0.065	0.1	-9999	-0.45	6	6
APPBP2	0.01	0.004	-9999	-10000	0	0
TRIM24	0.01	0.001	-9999	-10000	0	0
T-DHT/AR/TIP60	0.013	0.072	-9999	-0.32	8	8
TMPRSS2	-0.1	0.31	-9999	-1.1	39	39
RXRG	-0.26	0.25	-9999	-0.5	242	242
mol:9cRA	0	0	-9999	-10000	0	0
RXRA	0.01	0	-9999	-10000	0	0
RXRB	0.01	0	-9999	-10000	0	0
CARM1	0.01	0.002	-9999	-10000	0	0
NR2C2	0.01	0	-9999	-10000	0	0
KLK2	0.013	0.098	-9999	-0.39	8	8
AR	-0.012	0.11	-9999	-0.28	61	61
SENP1	0.01	0	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
MDM2	0.008	0.034	-9999	-0.51	2	2
SRY	0.001	0.004	-9999	-10000	0	0
GATA2	-0.035	0.14	-9999	-0.5	41	41
MYST2	0.01	0	-9999	-10000	0	0
HOXB13	-0.18	0.25	-9999	-0.51	169	169
T-DHT/AR/RACK1/Src	0.018	0.071	-9999	-0.38	3	3
positive regulation of transcription	-0.035	0.14	-9999	-0.5	41	41
DNAJA1	0.01	0.004	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.023	0.009	-9999	-10000	0	0
NCOA1	0.012	0.003	-9999	-10000	0	0
SPDEF	-0.17	0.25	-9999	-0.51	158	158
T-DHT/AR/TIF2	0.026	0.052	-9999	-10000	0	0
T-DHT/AR/Hsp90	0.013	0.072	-9999	-0.32	8	8
GSK3B	0.01	0.003	-9999	-10000	0	0
NR2C1	0.01	0	-9999	-10000	0	0
mol:T-DHT	0.017	0.062	-9999	-0.27	18	18
SIRT1	0.01	0	-9999	-10000	0	0
ZMIZ2	0.01	0.002	-9999	-10000	0	0
POU2F1	0.016	0.023	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.06	0.13	-9999	-0.37	37	37
CREBBP	0.01	0	-9999	-10000	0	0
SMARCE1	0.01	0.001	-9999	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.009	0.024	-9999	-0.5	1	1
PLK4	-0.019	0.12	-9999	-0.51	26	26
regulation of centriole replication	-0.004	0.089	-9999	-0.36	27	27

×

HIF-2-alpha transcription factor 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	-0.009	0.037	-10000	0	-10000	0	0
oxygen homeostasis	0	0.014	-10000	0	-10000	0	0
TCEB2	0.01	0	-10000	0	-10000	0	0
TCEB1	0.008	0.034	-10000	0	-0.51	2	2
VHL/Elongin B/Elongin C/HIF2A	-0.068	0.12	-10000	0	-0.4	30	30
EPO	-0.029	0.22	-10000	0	-0.64	14	14
FIH (dimer)	0.01	0.012	-10000	0	-10000	0	0
APEX1	0.012	0.012	-10000	0	-10000	0	0
SERPINE1	-0.051	0.26	-10000	0	-0.7	25	25
FLT1	-0.009	0.053	-10000	0	-0.89	1	1
ADORA2A	-0.046	0.25	-10000	0	-0.65	24	24
germ cell development	-0.062	0.26	-10000	0	-0.65	30	30
SLC11A2	-0.049	0.25	-10000	0	-0.67	24	24
BHLHE40	-0.049	0.25	-10000	0	-0.67	24	24
HIF1AN	0.01	0.012	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.089	0.14	-10000	0	-0.45	41	41
ETS1	0.021	0.025	-10000	0	-0.52	1	1
CITED2	-0.009	0.049	-10000	0	-0.96	1	1
KDR	-0.031	0.18	-10000	0	-1.2	11	11
PGK1	-0.049	0.25	-10000	0	-0.66	25	25
SIRT1	0.01	0	-10000	0	-10000	0	0
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	-0.051	0.29	-10000	0	-0.77	28	28
EPAS1	-0.046	0.17	-10000	0	-0.41	46	46
SP1	0.016	0.001	-10000	0	-10000	0	0
ABCG2	-0.075	0.3	-10000	0	-0.76	41	41
EFNA1	-0.049	0.26	-10000	0	-0.67	25	25
FXN	-0.046	0.25	-10000	0	-0.64	25	25
POU5F1	-0.066	0.27	-10000	0	-0.68	30	30
neuron apoptosis	0.049	0.28	0.74	28	-10000	0	28
EP300	0.01	0	-10000	0	-10000	0	0
EGLN3	-0.12	0.23	-10000	0	-0.52	119	119
EGLN2	0.01	0.012	-10000	0	-10000	0	0
EGLN1	0.011	0.012	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	-0.001	0.02	-10000	0	-0.3	2	2
VHL	0.01	0	-10000	0	-10000	0	0
ARNT	0.012	0.012	-10000	0	-10000	0	0
SLC2A1	-0.12	0.32	-10000	0	-0.66	73	73
TWIST1	-0.086	0.3	-10000	0	-0.67	55	55
ELK1	0.016	0.004	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.087	0.14	-10000	0	-0.44	40	40
VEGFA	-0.049	0.25	-10000	0	-0.66	26	26
CREBBP	0.01	0	-10000	0	-10000	0	0

×

Coregulation of Androgen receptor activity

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.01	0.001	-9999	-10000	0	0
SVIL	0.01	0.001	-9999	-10000	0	0
ZNF318	0.009	0.008	-9999	-10000	0	0
JMJD2C	-0.001	0.018	-9999	-0.078	24	24
T-DHT/AR/Ubc9	-0.045	0.12	-9999	-0.33	63	63
CARM1	0.01	0	-9999	-10000	0	0
PRDX1	0.009	0.024	-9999	-0.51	1	1
PELP1	0.01	0.001	-9999	-10000	0	0
CTNNB1	0.01	0.001	-9999	-10000	0	0
AKT1	0.01	0.002	-9999	-10000	0	0
PTK2B	0.008	0.033	-9999	-0.5	2	2
MED1	0.01	0.002	-9999	-10000	0	0
MAK	-0.008	0.09	-9999	-0.5	15	15
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	0.004	0.052	-9999	-0.5	5	5
GSN	0.01	0.001	-9999	-10000	0	0
NCOA2	0.005	0.047	-9999	-0.5	4	4
NCOA6	0.01	0.001	-9999	-10000	0	0
DNA-PK	0.001	0.009	-9999	-10000	0	0
NCOA4	0.01	0	-9999	-10000	0	0
PIAS3	0.01	0.001	-9999	-10000	0	0
cell proliferation	-0.035	0.13	-9999	-0.73	15	15
XRCC5	0.01	0.001	-9999	-10000	0	0
UBE3A	0.01	0.003	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.058	0.13	-9999	-0.33	80	80
FHL2	-0.054	0.13	-9999	-0.44	21	21
RANBP9	0.01	0.001	-9999	-10000	0	0
JMJD1A	0	0.041	-9999	-0.12	44	44
CDK6	0.008	0.034	-9999	-0.51	2	2
TGFB1I1	0.007	0.041	-9999	-0.5	3	3
T-DHT/AR/CyclinD1	-0.048	0.12	-9999	-0.33	68	68
XRCC6	0.01	0.001	-9999	-10000	0	0
T-DHT/AR	-0.041	0.14	-9999	-0.34	71	71
CTDSP1	0.01	0.001	-9999	-10000	0	0
CTDSP2	0.01	0.004	-9999	-10000	0	0
BRCA1	0.008	0.034	-9999	-0.51	2	2
TCF4	0.008	0.033	-9999	-0.5	2	2
CDKN2A	-0.15	0.24	-9999	-0.51	142	142
SRF	0.005	0.027	-9999	-10000	0	0
NKX3-1	-0.047	0.13	-9999	-0.95	6	6
KLK3	0.016	0.047	-9999	-10000	0	0
TMF1	0.01	0.001	-9999	-10000	0	0
HNRNPA1	0.01	0.002	-9999	-10000	0	0
AOF2	0	0.003	-9999	-10000	0	0
APPL1	0.018	0.004	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.048	0.12	-9999	-0.33	64	64
AR	-0.066	0.18	-9999	-0.52	63	63
UBA3	0.01	0.001	-9999	-10000	0	0
PATZ1	0.01	0.002	-9999	-10000	0	0
PAWR	0.01	0.001	-9999	-10000	0	0
PRKDC	0.01	0.001	-9999	-10000	0	0
PA2G4	0.01	0.003	-9999	-10000	0	0
UBE2I	0.01	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.034	0.11	-9999	-0.3	63	63
RPS6KA3	0.01	0.001	-9999	-10000	0	0
T-DHT/AR/ARA70	-0.044	0.12	-9999	-0.33	63	63
LATS2	0.01	0.002	-9999	-10000	0	0
T-DHT/AR/PRX1	-0.036	0.11	-9999	-0.3	63	63
Cyclin D3/CDK11 p58	0	0	-9999	-10000	0	0
VAV3	0.003	0.058	-9999	-0.5	6	6
KLK2	-0.043	0.091	-9999	-0.37	24	24
CASP8	0.009	0.024	-9999	-0.5	1	1
T-DHT/AR/TIF2/CARM1	-0.037	0.11	-9999	-0.29	67	67
TMPRSS2	-0.098	0.27	-9999	-0.98	39	39
CCND1	0.003	0.057	-9999	-0.5	6	6
PIAS1	0.01	0.003	-9999	-10000	0	0
mol:T-DHT	-0.008	0.026	-9999	-0.077	34	34
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.01	0.006	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.048	0.12	-9999	-0.33	65	65
CMTM2	-0.092	0.2	-9999	-0.5	93	93
SNURF	-0.011	0.1	-9999	-0.5	19	19
ZMIZ1	0.004	0.023	-9999	-10000	0	0
CCND3	0.01	0	-9999	-10000	0	0
TGIF1	0.01	0.002	-9999	-10000	0	0
FKBP4	0.009	0.024	-9999	-0.51	1	1

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.014	0.044	-9999	-0.33	7	7
EPHB2	-0.049	0.17	-9999	-0.51	53	53
Syndecan-2/TACI	-0.008	0.088	-9999	-0.3	39	39
LAMA1	-0.019	0.12	-9999	-0.51	26	26
Syndecan-2/alpha2 ITGB1	-0.057	0.11	-9999	-0.5	5	5
HRAS	0.01	0	-9999	-10000	0	0
Syndecan-2/CASK	-0.003	0.027	-9999	-0.3	4	4
ITGA5	0.008	0.034	-9999	-0.51	2	2
BAX	0.029	0.026	-9999	-10000	0	0
EPB41	0.01	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.002	0.024	-9999	-0.26	4	4
LAMA3	-0.092	0.2	-9999	-0.5	93	93
EZR	0.01	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.093	0.2	-9999	-0.5	94	94
Syndecan-2/MMP2	0.016	0.032	-9999	-0.29	5	5
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.012	0.064	-9999	-0.36	15	15
dendrite morphogenesis	-0.02	0.1	-9999	-0.3	57	57
Syndecan-2/GM-CSF	-0.009	0.091	-9999	-0.3	41	41
determination of left/right symmetry	0.013	0.034	-9999	-0.35	4	4
Syndecan-2/PKC delta	0.017	0.029	-9999	-0.29	4	4
GNB2L1	0.01	0	-9999	-10000	0	0
MAPK3	0	0.083	-9999	-0.27	41	41
MAPK1	0	0.083	-9999	-0.27	41	41
Syndecan-2/RACK1	-0.002	0.022	-9999	-0.24	4	4
NF1	0.01	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.013	0.034	-9999	-0.35	4	4
ITGA2	-0.007	0.092	-9999	-0.51	15	15
MAPK8	0.025	0.029	-9999	-0.29	4	4
Syndecan-2/alpha2/beta1 Integrin	-0.024	0.081	-9999	-0.5	5	5
Syndecan-2/Kininogen	-0.014	0.082	-9999	-0.3	35	35
ITGB1	0.01	0	-9999	-10000	0	0
SRC	0.027	0.023	-9999	-10000	0	0
Syndecan-2/CASK/Protein 4.1	-0.002	0.024	-9999	-0.26	4	4
extracellular matrix organization	0.016	0.028	-9999	-0.29	4	4
actin cytoskeleton reorganization	0.014	0.044	-9999	-0.33	7	7
Syndecan-2/Caveolin-2/Ras	-0.054	0.1	-9999	-0.26	98	98
Syndecan-2/Laminin alpha3	-0.046	0.13	-9999	-0.29	97	97
Syndecan-2/RasGAP	-0.002	0.021	-9999	-10000	0	0
alpha5/beta1 Integrin	-0.002	0.023	-9999	-0.36	2	2
PRKCD	0.01	0	-9999	-10000	0	0
Syndecan-2 dimer	-0.02	0.1	-9999	-0.3	57	57
GO:0007205	0.003	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.032	0.023	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
SDCBP	0.01	0	-9999	-10000	0	0
TNFRSF13B	-0.029	0.14	-9999	-0.51	35	35
RASA1	0.01	0	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.012	0.064	-9999	-0.36	15	15
Syndecan-2/Synbindin	0.017	0.029	-9999	-0.29	4	4
TGFB1	0.01	0	-9999	-10000	0	0
CASP3	0.023	0.026	-9999	-0.26	4	4
FN1	0.005	0.047	-9999	-0.5	4	4
Syndecan-2/IL8	0.002	0.072	-9999	-0.3	25	25
SDC2	0.013	0.034	-9999	-0.35	4	4
KNG1	-0.03	0.13	-9999	-0.51	31	31
Syndecan-2/Neurofibromin	0.017	0.029	-9999	-0.29	4	4
TRAPPC4	0.01	0	-9999	-10000	0	0
CSF2	-0.032	0.14	-9999	-0.5	38	38
Syndecan-2/TGFB1	0.017	0.029	-9999	-0.29	4	4
Syndecan-2/Syntenin/PI-4-5-P2	-0.002	0.024	-9999	-0.26	4	4
Syndecan-2/Ezrin	-0.002	0.024	-9999	-0.26	4	4
PRKACA	0.023	0.026	-9999	-0.26	4	4
angiogenesis	0.002	0.071	-9999	-0.3	25	25
MMP2	0.009	0.024	-9999	-0.51	1	1
IL8	-0.014	0.11	-9999	-0.51	21	21
calcineurin-NFAT signaling pathway	-0.008	0.088	-9999	-0.3	39	39

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	-0.011	0.062	-9999	-0.36	14	14
VLDLR	-0.001	0.074	-9999	-0.5	10	10
CRKL	0.01	0	-9999	-10000	0	0
LRPAP1	0.01	0	-9999	-10000	0	0
FYN	0.009	0.024	-9999	-0.5	1	1
ITGA3	0.005	0.047	-9999	-0.5	4	4
RELN/VLDLR/Fyn	-0.051	0.12	-9999	-0.32	76	76
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.001	0.011	-9999	-10000	0	0
AKT1	-0.015	0.097	-9999	-0.41	7	7
MAP2K7	0.01	0	-9999	-10000	0	0
RAPGEF1	0.01	0	-9999	-10000	0	0
DAB1	-0.003	0.067	-9999	-0.51	8	8
RELN/LRP8/DAB1	-0.052	0.11	-9999	-0.28	86	86
LRPAP1/LRP8	-0.009	0.055	-9999	-0.36	11	11
RELN/LRP8/DAB1/Fyn	-0.048	0.1	-9999	-0.27	57	57
DAB1/alpha3/beta1 Integrin	-0.048	0.1	-9999	-0.45	10	10
long-term memory	-0.096	0.14	-9999	-0.51	25	25
DAB1/LIS1	-0.048	0.1	-9999	-0.47	9	9
DAB1/CRLK/C3G	-0.046	0.099	-9999	-0.45	9	9
PIK3CA	0.01	0	-9999	-10000	0	0
DAB1/NCK2	-0.049	0.1	-9999	-0.47	9	9
ARHGEF2	0.01	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.092	0.2	-9999	-0.51	92	92
CDK5R1	-0.006	0.089	-9999	-0.51	14	14
RELN	-0.068	0.18	-9999	-0.5	71	71
PIK3R1	0.009	0.024	-9999	-0.5	1	1
RELN/LRP8/Fyn	-0.052	0.11	-9999	-0.3	82	82
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.095	0.14	-9999	-0.52	21	21
MAPK8	0.01	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.051	0.12	-9999	-0.3	81	81
ITGB1	0.01	0	-9999	-10000	0	0
MAP1B	-0.032	0.12	-9999	-0.48	12	12
RELN/LRP8	-0.051	0.11	-9999	-0.29	82	82
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.053	0.11	-9999	-0.5	10	10
PI3K	-0.001	0.016	-9999	-0.35	1	1
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.003	0.033	-9999	-0.35	4	4
RAP1A	-0.008	0.11	-9999	-0.42	9	9
PAFAH1B1	0.01	0	-9999	-10000	0	0
MAPK8IP1	0.01	0	-9999	-10000	0	0
CRLK/C3G	0	0	-9999	-10000	0	0
GRIN2B	-0.009	0.075	-9999	-0.51	10	10
NCK2	0.01	0	-9999	-10000	0	0
neuron differentiation	0.001	0.072	-9999	-0.31	3	3
neuron adhesion	0.002	0.11	-9999	-0.4	10	10
LRP8	-0.002	0.079	-9999	-0.51	11	11
GSK3B	-0.008	0.093	-9999	-0.38	7	7
RELN/VLDLR/DAB1/Fyn	-0.048	0.11	-9999	-0.44	12	12
MAP3K11	0.009	0.024	-9999	-0.5	1	1
RELN/VLDLR/DAB1/P13K	-0.023	0.1	-9999	-0.42	8	8
CDK5	0.01	0	-9999	-10000	0	0
MAPT	-0.019	0.11	-9999	-0.46	27	27
neuron migration	-0.009	0.12	-9999	-0.44	9	9
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	0.001	0.073	-9999	-0.31	3	3
RELN/VLDLR	-0.051	0.11	-9999	-0.52	5	5

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.01	0.048	-9999	-0.48	4	4
Syndecan-4/Syndesmos	-0.021	0.085	-9999	-0.52	2	2
positive regulation of JNK cascade	-0.052	0.084	-9999	-0.44	4	4
Syndecan-4/ADAM12	-0.11	0.16	-9999	-0.38	78	78
CCL5	0.004	0.052	-9999	-0.5	5	5
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0.01	0	-9999	-10000	0	0
ITGA5	0.008	0.034	-9999	-0.51	2	2
SDCBP	0.01	0	-9999	-10000	0	0
PLG	-0.007	0.072	-9999	-0.52	9	9
ADAM12	-0.17	0.25	-9999	-0.51	162	162
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.01	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.034	0.05	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.035	0.11	-9999	-0.47	6	6
Syndecan-4/CXCL12/CXCR4	-0.033	0.1	-9999	-0.47	4	4
Syndecan-4/Laminin alpha3	-0.069	0.13	-9999	-0.37	31	31
MDK	-0.15	0.24	-9999	-0.51	145	145
Syndecan-4/FZD7	-0.021	0.087	-9999	-0.52	2	2
Syndecan-4/Midkine	-0.099	0.14	-9999	-0.38	53	53
FZD7	0.009	0.024	-9999	-0.5	1	1
Syndecan-4/FGFR1/FGF	-0.067	0.1	-9999	-0.49	9	9
THBS1	0.007	0.041	-9999	-0.5	3	3
integrin-mediated signaling pathway	-0.038	0.1	-9999	-0.4	11	11
positive regulation of MAPKKK cascade	-0.052	0.084	-9999	-0.44	4	4
Syndecan-4/TACI	-0.04	0.11	-9999	-0.38	20	20
CXCR4	0.01	0	-9999	-10000	0	0
cell adhesion	0.005	0.039	-9999	-0.33	4	4
Syndecan-4/Dynamin	-0.021	0.085	-9999	-0.52	2	2
Syndecan-4/TSP1	-0.022	0.09	-9999	-0.63	2	2
Syndecan-4/GIPC	-0.021	0.085	-9999	-0.52	2	2
Syndecan-4/RANTES	-0.024	0.087	-9999	-0.52	2	2
ITGB1	0.01	0	-9999	-10000	0	0
LAMA1	-0.019	0.12	-9999	-0.51	26	26
LAMA3	-0.092	0.2	-9999	-0.5	93	93
RAC1	0.01	0	-9999	-10000	0	0
PRKCA	0.015	0.04	-9999	-0.46	2	2
Syndecan-4/alpha-Actinin	-0.021	0.085	-9999	-0.52	2	2
TFPI	-0.009	0.096	-9999	-0.5	17	17
F2	-0.069	0.18	-9999	-0.52	65	65
alpha5/beta1 Integrin	-0.002	0.023	-9999	-0.36	2	2
positive regulation of cell adhesion	-0.075	0.14	-9999	-0.49	10	10
ACTN1	0.01	0	-9999	-10000	0	0
TNC	-0.029	0.14	-9999	-0.51	35	35
Syndecan-4/CXCL12	-0.037	0.1	-9999	-0.48	4	4
FGF6	0	0.001	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
CXCL12	-0.023	0.12	-9999	-0.5	30	30
TNFRSF13B	-0.029	0.14	-9999	-0.51	35	35
FGF2	-0.057	0.17	-9999	-0.5	61	61
FGFR1	0.007	0.041	-9999	-0.5	3	3
Syndecan-4/PI-4-5-P2	-0.027	0.085	-9999	-0.53	2	2
mol:GDP	0	0	-9999	-10000	0	0
FN1	0.007	0.046	-9999	-0.48	4	4
cell migration	-0.014	0.021	-9999	-10000	0	0
PRKCD	0.012	0.006	-9999	-10000	0	0
vasculogenesis	-0.022	0.087	-9999	-0.6	2	2
SDC4	-0.028	0.09	-9999	-0.56	2	2
Syndecan-4/Tenascin C	-0.04	0.11	-9999	-0.42	10	10
Syndecan-4/PI-4-5-P2/PKC alpha	-0.027	0.039	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.021	0.085	-9999	-0.52	2	2
MMP9	-0.095	0.21	-9999	-0.52	93	93
Rac1/GTP	0.005	0.04	-9999	-0.34	4	4
cytoskeleton organization	-0.02	0.083	-9999	-0.5	2	2
GIPC1	0.01	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.03	0.097	-9999	-0.46	5	5

×

Noncanonical Wnt signaling pathway

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
NFATC2	-0.012	0.1	-9999	-0.5	20	20
GNB1/GNG2	-0.048	0.1	-9999	-0.44	15	15
mol:DAG	-0.011	0.11	-9999	-0.39	15	15
PLCG1	-0.011	0.11	-9999	-0.41	15	15
YES1	-0.024	0.12	-9999	-0.44	15	15
FZD3	0.009	0.024	-9999	-0.51	1	1
FZD6	0.009	0.024	-9999	-0.5	1	1
G protein	-0.042	0.097	-9999	-0.41	15	15
MAP3K7	-0.018	0.12	-9999	-0.39	27	27
mol:Ca2+	-0.01	0.1	-9999	-0.38	15	15
mol:IP3	-0.011	0.11	-9999	-0.39	15	15
NLK	-0.002	0.006	-9999	-10000	0	0
GNB1	0.01	0	-9999	-10000	0	0
CAMK2A	-0.027	0.13	-9999	-0.42	29	29
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.032	0.12	-9999	-0.41	20	20
CSNK1A1	0.01	0	-9999	-10000	0	0
GNAS	-0.024	0.12	-9999	-0.44	15	15
GO:0007205	-0.01	0.11	-9999	-0.39	15	15
WNT6	-0.021	0.12	-9999	-0.51	27	27
WNT4	-0.022	0.12	-9999	-0.5	29	29
NFAT1/CK1 alpha	-0.05	0.1	-9999	-0.42	16	16
GNG2	0.008	0.033	-9999	-0.5	2	2
WNT5A	0.004	0.052	-9999	-0.5	5	5
WNT11	-0.061	0.18	-9999	-0.5	65	65
CDC42	-0.016	0.11	-9999	-0.41	15	15

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.009	0.024	-9999	-0.5	1	1
alphaV beta3 Integrin	-0.021	0.084	-9999	-0.36	27	27
PTK2	-0.037	0.11	-9999	-0.39	34	34
positive regulation of JNK cascade	-0.022	0.074	-9999	-0.29	34	34
CDC42/GDP	0.011	0.11	-9999	-0.38	34	34
Rac1/GDP	0.013	0.11	-9999	-0.38	34	34
RAP1B	0.01	0	-9999	-10000	0	0
RAP1A	0.01	0	-9999	-10000	0	0
CTNNB1	0.01	0	-9999	-10000	0	0
CDC42/GTP	-0.026	0.091	-9999	-0.35	34	34
nectin-3/I-afadin	-0.026	0.093	-9999	-0.35	35	35
RAPGEF1	0.006	0.12	-9999	-0.42	34	34
mol:GTP	0	0	-9999	-10000	0	0
CRK	-0.002	0.14	-9999	-0.48	34	34
PDGFB-D/PDGFRB	0.009	0.024	-9999	-0.5	1	1
TLN1	0.003	0.085	-9999	-0.39	14	14
Rap1/GTP	-0.022	0.078	-9999	-0.3	34	34
IQGAP1	0.01	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.026	0.093	-9999	-0.35	35	35
PVR	0.01	0	-9999	-10000	0	0
Necl-5(dimer)	0.01	0	-9999	-10000	0	0
mol:GDP	0.006	0.13	-9999	-0.46	34	34
MLLT4	0.01	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
PI3K	-0.019	0.068	-9999	-0.49	2	2
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.009	0.055	-9999	-0.36	11	11
positive regulation of lamellipodium assembly	-0.023	0.079	-9999	-0.3	35	35
PVRL1	-0.002	0.079	-9999	-0.51	11	11
PVRL3	-0.028	0.13	-9999	-0.5	35	35
PVRL2	0.01	0	-9999	-10000	0	0
PIK3R1	0.009	0.024	-9999	-0.5	1	1
CDH1	0.008	0.033	-9999	-0.5	2	2
CLDN1	-0.01	0.1	-9999	-0.51	18	18
JAM-A/CLDN1	-0.03	0.09	-9999	-0.52	4	4
SRC	-0.042	0.14	-9999	-0.53	34	34
ITGB3	-0.02	0.12	-9999	-0.51	27	27
nectin-1(dimer)/I-afadin/I-afadin	-0.009	0.055	-9999	-0.36	11	11
FARP2	0.002	0.13	-9999	-0.46	34	34
RAC1	0.01	0	-9999	-10000	0	0
CTNNA1	0.01	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.022	0.077	-9999	-0.29	35	35
nectin-1/I-afadin	-0.009	0.055	-9999	-0.36	11	11
nectin-2/I-afadin	0	0	-9999	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.029	0.09	-9999	-0.3	45	45
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0.009	0.024	-9999	-0.5	1	1
positive regulation of filopodium formation	-0.022	0.074	-9999	-0.29	34	34
alphaV/beta3 Integrin/Talin	-0.001	0.098	-9999	-0.48	8	8
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
PIP5K1C	-0.003	0.089	-9999	-0.44	13	13
VAV2	0	0.13	-9999	-0.47	35	35
RAP1/GDP	-0.026	0.092	-9999	-0.35	34	34
ITGAV	0.01	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.022	0.077	-9999	-0.29	35	35
nectin-3(dimer)/I-afadin/I-afadin	-0.026	0.093	-9999	-0.35	35	35
Rac1/GTP	-0.028	0.095	-9999	-0.36	35	35
PTPRM	-0.025	0.093	-9999	-0.48	13	13
E-cadherin/beta catenin/alpha catenin	-0.006	0.037	-9999	-10000	0	0
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.01	0	-9999	-10000	0	0

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	0.024	0.094	-10000	0	-0.36	11	11
TBX21	-0.007	0.34	-10000	0	-1.2	28	28
B2M	0.011	0.005	-10000	0	-10000	0	0
TYK2	0.017	0.015	-10000	0	-10000	0	0
IL12RB1	0.001	0.096	-10000	0	-0.52	15	15
GADD45B	0.014	0.27	-10000	0	-1.1	18	18
IL12RB2	-0.026	0.15	-10000	0	-0.51	40	40
GADD45G	0.013	0.28	-10000	0	-1	21	21
natural killer cell activation	0.008	0.016	-10000	0	-10000	0	0
RELB	0.01	0	-10000	0	-10000	0	0
RELA	0.01	0	-10000	0	-10000	0	0
IL18	0.004	0.071	-10000	0	-0.5	9	9
IL2RA	-0.028	0.14	-10000	0	-0.51	34	34
IFNG	-0.034	0.14	-10000	0	-0.51	39	39
STAT3 (dimer)	0.025	0.23	-10000	0	-0.8	20	20
HLA-DRB5	-0.043	0.16	-10000	0	-0.5	49	49
FASLG	0.012	0.29	-10000	0	-1.1	21	21
NF kappa B2 p52/RelB	-0.083	0.22	-10000	0	-0.91	23	23
CD4	-0.001	0.074	-10000	0	-0.5	10	10
SOCS1	0.01	0	-10000	0	-10000	0	0
EntrezGene:6955	0	0.008	-10000	0	-10000	0	0
CD3D	0.008	0.042	-10000	0	-0.51	3	3
CD3E	0.006	0.053	-10000	0	-0.5	5	5
CD3G	0	0.075	-10000	0	-0.5	10	10
IL12Rbeta2/JAK2	-0.004	0.11	-10000	0	-0.36	41	41
CCL3	0.016	0.27	-10000	0	-0.98	21	21
CCL4	0.014	0.28	-10000	0	-1	20	20
HLA-A	0.011	0.004	-10000	0	-10000	0	0
IL18/IL18R	0.017	0.12	-10000	0	-0.36	38	38
NOS2	-0.045	0.41	-10000	0	-1.2	49	49
IL12/IL12R/TYK2/JAK2/SPHK2	0.023	0.094	-10000	0	-0.36	11	11
IL1R1	0.016	0.28	-10000	0	-1	20	20
IL4	-0.004	0.016	-10000	0	-10000	0	0
JAK2	0.016	0.028	-10000	0	-0.5	1	1
EntrezGene:6957	0	0.008	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	0.013	0.16	-10000	0	-1	9	9
RAB7A	0.035	0.23	-10000	0	-0.82	15	15
lysosomal transport	0.037	0.22	-10000	0	-0.77	15	15
FOS	-0.049	0.35	-10000	0	-1.1	40	40
STAT4 (dimer)	0.033	0.26	-10000	0	-0.89	21	21
STAT5A (dimer)	-0.097	0.23	-10000	0	-0.88	27	27
GZMA	0.012	0.29	-10000	0	-1.1	20	20
GZMB	-0.001	0.32	-10000	0	-1.1	26	26
HLX	0.004	0.053	-10000	0	-0.5	5	5
LCK	0.014	0.29	-10000	0	-1.1	21	21
TCR/CD3/MHC II/CD4	-0.024	0.17	-10000	0	-0.56	29	29
IL2/IL2R	-0.023	0.081	-10000	0	-0.28	39	39
MAPK14	0.021	0.28	-10000	0	-0.99	19	19
CCR5	0.015	0.27	-10000	0	-1.1	17	17
IL1B	-0.012	0.12	-10000	0	-0.51	26	26
STAT6	0.029	0.085	-10000	0	-0.26	4	4
STAT4	0.01	0	-10000	0	-10000	0	0
STAT3	0.01	0	-10000	0	-10000	0	0
STAT1	0.01	0	-10000	0	-10000	0	0
NFKB1	0.01	0	-10000	0	-10000	0	0
NFKB2	0.01	0	-10000	0	-10000	0	0
IL12B	0.013	0.057	-10000	0	-0.52	5	5
CD8A	0.004	0.058	-10000	0	-0.51	6	6
CD8B	0.003	0.063	-10000	0	-0.51	7	7
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.024	0.093	0.35	11	-10000	0	11
IL2RB	0.008	0.033	-10000	0	-0.5	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.038	0.24	-10000	0	-0.81	20	20
IL2RG	0.004	0.052	-10000	0	-0.5	5	5
IL12	0.021	0.065	-10000	0	-0.37	11	11
STAT5A	0.009	0.024	-10000	0	-0.5	1	1
CD247	0.004	0.058	-10000	0	-0.5	6	6
IL2	0.006	0.005	-10000	0	-10000	0	0
SPHK2	0.009	0.024	-10000	0	-0.5	1	1
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.011	0.061	-10000	0	-0.51	6	6
IL12/IL12R/TYK2/JAK2	0.008	0.32	-10000	0	-1.1	23	23
MAP2K3	0.018	0.28	-10000	0	-0.98	20	20
RIPK2	0.01	0	-10000	0	-10000	0	0
MAP2K6	0.016	0.28	-10000	0	-0.95	22	22
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.012	0.1	-10000	0	-0.5	20	20
IL18RAP	-0.006	0.1	-10000	0	-0.5	18	18
IL12Rbeta1/TYK2	0.013	0.074	-10000	0	-0.38	15	15
EOMES	-0.008	0.14	-10000	0	-1.2	6	6
STAT1 (dimer)	0.018	0.24	-10000	0	-0.79	21	21
T cell proliferation	0.03	0.21	-10000	0	-0.68	19	19
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.008	0.1	-10000	0	-0.5	20	20
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.077	0.18	-10000	0	-0.74	20	20
ATF2	0.028	0.25	-10000	0	-0.88	19	19

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	0.02	0.096	-10000	0	-0.4	20	20
CRKL	0.017	0.095	-10000	0	-0.42	19	19
HRAS	0.029	0.1	-10000	0	-0.38	22	22
mol:PIP3	0.005	0.091	-10000	0	-0.41	19	19
SPRED1	0.01	0	-10000	0	-10000	0	0
SPRED2	0.01	0	-10000	0	-10000	0	0
GAB1	0.011	0.1	-10000	0	-0.45	19	19
FOXO3	0.021	0.087	-10000	0	-0.38	19	19
AKT1	0.015	0.094	-10000	0	-0.42	19	19
BAD	0.021	0.087	-10000	0	-0.38	19	19
megakaryocyte differentiation	-0.011	0.13	-10000	0	-0.47	24	24
GSK3B	0.021	0.087	-10000	0	-0.38	19	19
RAF1	0.034	0.084	-10000	0	-0.38	9	9
SHC1	0.01	0	-10000	0	-10000	0	0
STAT3	0.011	0.099	-10000	0	-0.45	19	19
STAT1	0.009	0.21	-10000	0	-0.95	20	20
HRAS/SPRED1	-0.019	0.07	-10000	0	-0.31	22	22
cell proliferation	0.012	0.098	-10000	0	-0.44	19	19
PIK3CA	0.01	0	-10000	0	-10000	0	0
TEC	0.01	0	-10000	0	-10000	0	0
RPS6KB1	0.011	0.1	-10000	0	-0.45	19	19
HRAS/SPRED2	-0.019	0.07	-10000	0	-0.38	9	9
LYN/TEC/p62DOK	-0.019	0.085	-10000	0	-0.42	19	19
MAPK3	0.038	0.063	-10000	0	-0.27	7	7
STAP1	0.004	0.11	-10000	0	-0.44	22	22
GRAP2	-0.005	0.087	-10000	0	-0.5	14	14
JAK2	-0.038	0.17	-10000	0	-0.82	20	20
STAT1 (dimer)	0.01	0.2	-10000	0	-0.93	20	20
mol:Gleevec	-0.002	0.004	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.021	0.088	-10000	0	-0.41	20	20
actin filament polymerization	0.011	0.098	-10000	0	-0.44	19	19
LYN	0.01	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	0.012	0.14	-10000	0	-0.58	22	22
PIK3R1	0.009	0.024	-10000	0	-0.5	1	1
CBL/CRKL/GRB2	-0.018	0.078	-10000	0	-0.38	19	19
PI3K	-0.02	0.087	-10000	0	-0.42	19	19
PTEN	0.01	0	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	0.006	0.25	-10000	0	-1.2	19	19
MAPK8	0.011	0.099	-10000	0	-0.45	19	19
STAT3 (dimer)	0.012	0.098	-10000	0	-0.44	19	19
positive regulation of transcription	0.036	0.053	-10000	0	-0.22	7	7
mol:GDP	-0.024	0.09	-10000	0	-0.4	22	22
PIK3C2B	0.01	0.1	-10000	0	-0.46	19	19
CBL/CRKL	0.022	0.09	-10000	0	-0.39	19	19
FER	0.011	0.099	-10000	0	-0.45	19	19
SH2B3	0.01	0.1	-10000	0	-0.45	20	20
PDPK1	0.01	0.085	-10000	0	-0.38	19	19
SNAI2	0.009	0.11	-10000	0	-0.47	20	20
positive regulation of cell proliferation	0.014	0.16	-10000	0	-0.72	20	20
KITLG	0.009	0.05	-10000	0	-0.53	4	4
cell motility	0.014	0.16	-10000	0	-0.72	20	20
PTPN6	0.002	0.007	-10000	0	-10000	0	0
EPOR	0.031	0.063	-10000	0	-10000	0	0
STAT5A (dimer)	0.015	0.14	-10000	0	-0.61	19	19
SOCS1	0.01	0	-10000	0	-10000	0	0
cell migration	0	0.11	0.45	20	-10000	0	20
SOS1	0.01	0	-10000	0	-10000	0	0
EPO	0.005	0.042	-10000	0	-0.52	3	3
VAV1	0.004	0.052	-10000	0	-0.5	5	5
GRB10	0.011	0.099	-10000	0	-0.45	19	19
PTPN11	0.009	0.004	-10000	0	-10000	0	0
SCF/KIT	0.005	0.1	-10000	0	-0.48	19	19
GO:0007205	-0.002	0.005	-10000	0	-10000	0	0
MAP2K1	0.037	0.068	-10000	0	-0.3	7	7
CBL	0.01	0	-10000	0	-10000	0	0
KIT	-0.01	0.25	-10000	0	-1.2	19	19
MAP2K2	0.037	0.068	-10000	0	-0.3	7	7
SHC/Grb2/SOS1	-0.019	0.085	-10000	0	-0.42	19	19
STAT5A	0.015	0.14	-10000	0	-0.63	19	19
GRB2	0.01	0	-10000	0	-10000	0	0
response to radiation	0.009	0.1	-10000	0	-0.46	20	20
SHC/GRAP2	-0.011	0.06	-10000	0	-0.35	14	14
PTPRO	-0.012	0.13	-10000	0	-0.48	24	24
SH2B2	0.011	0.1	-10000	0	-0.45	19	19
DOK1	0.01	0	-10000	0	-10000	0	0
MATK	0	0.11	-10000	0	-0.46	20	20
CREBBP	0.029	0.007	-10000	0	-10000	0	0
BCL2	0.028	0.086	-10000	0	-1.2	1	1

×

Caspase cascade in apoptosis

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
TOP1	0.004	0.084	-10000	0	-0.29	32	32
ACTA1	-0.008	0.11	-10000	0	-0.37	32	32
NUMA1	0.004	0.084	-10000	0	-0.29	32	32
SPTAN1	-0.004	0.1	-10000	0	-0.36	32	32
LIMK1	-0.004	0.1	-10000	0	-0.36	32	32
BIRC3	0.003	0.058	-10000	0	-0.51	6	6
BIRC2	0.01	0	-10000	0	-10000	0	0
BAX	0.01	0	-10000	0	-10000	0	0
CASP10	-0.002	0.096	-10000	0	-0.33	34	34
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.01	0	-10000	0	-10000	0	0
PTK2	0.004	0.084	-10000	0	-0.29	32	32
DIABLO	0.01	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.004	0.1	-10000	0	-0.36	32	32
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.009	0.024	-10000	0	-0.51	1	1
GSN	-0.004	0.1	-10000	0	-0.37	32	32
MADD	0.01	0	-10000	0	-10000	0	0
TFAP2A	-0.041	0.12	-10000	0	-0.64	18	18
BID	0.004	0.058	-10000	0	-0.2	33	33
MAP3K1	0.004	0.038	-10000	0	-0.2	5	5
TRADD	0.01	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0	0.002	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.004	0.1	-10000	0	-0.36	32	32
CASP9	0.01	0	-10000	0	-10000	0	0
DNA repair	-0.002	0.028	-10000	0	-10000	0	0
neuron apoptosis	0.017	0.021	-10000	0	-0.35	1	1
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.002	0.1	-10000	0	-0.35	32	32
APAF1	0.01	0	-10000	0	-10000	0	0
CASP6	0.016	0.053	-10000	0	-0.32	1	1
TRAF2	0.01	0	-10000	0	-10000	0	0
ICAD/CAD	0.002	0.1	-10000	0	-0.35	32	32
CASP7	-0.005	0.029	0.22	6	-10000	0	6
KRT18	0.012	0.017	-10000	0	-10000	0	0
apoptosis	0.007	0.091	-10000	0	-0.48	7	7
DFFA	-0.004	0.1	-10000	0	-0.36	32	32
DFFB	-0.004	0.1	-10000	0	-0.36	32	32
PARP1	0.002	0.028	-10000	0	-10000	0	0
actin filament polymerization	-0.003	0.097	0.34	32	-10000	0	32
TNF	-0.011	0.1	-10000	0	-0.5	19	19
CYCS	0.008	0.041	-10000	0	-0.22	5	5
SATB1	0.016	0.066	-10000	0	-0.38	4	4
SLK	-0.004	0.1	-10000	0	-0.36	32	32
p15 BID/BAX	0.009	0.051	-10000	0	-0.28	5	5
CASP2	0.03	0.044	-10000	0	-10000	0	0
JNK cascade	-0.004	0.037	0.2	5	-10000	0	5
CASP3	-0.011	0.11	-10000	0	-0.39	32	32
LMNB2	0.029	0.038	-10000	0	-10000	0	0
RIPK1	0.01	0	-10000	0	-10000	0	0
CASP4	0.01	0	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	-0.003	0.03	-10000	0	-0.27	4	4
negative regulation of DNA binding	-0.041	0.12	-10000	0	-0.63	18	18
stress fiber formation	-0.004	0.1	-10000	0	-0.36	32	32
GZMB	-0.011	0.11	-10000	0	-0.4	32	32
CASP1	0.011	0.03	-10000	0	-0.31	4	4
LMNB1	0.028	0.038	-10000	0	-10000	0	0
APP	0.017	0.021	-10000	0	-0.35	1	1
TNFRSF1A	0.01	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.008	0.017	-10000	0	-0.36	1	1
VIM	0.002	0.089	-10000	0	-0.3	32	32
LMNA	0.029	0.038	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.025	0.046	-10000	0	-10000	0	0
LRDD	0.008	0.033	-10000	0	-0.5	2	2
SREBF1	-0.004	0.1	-10000	0	-0.36	32	32
APAF-1/Caspase 9	-0.003	0.017	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0.004	0.083	-10000	0	-0.29	32	32
CFL2	0.002	0.1	-10000	0	-0.34	32	32
GAS2	-0.018	0.12	-10000	0	-0.38	33	33
positive regulation of apoptosis	0.031	0.038	-10000	0	-10000	0	0
PRF1	-0.014	0.11	-10000	0	-0.5	22	22

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.009	0.024	-10000	0	-0.5	1	1
Jak2/Leptin Receptor	-0.035	0.089	0.17	3	-0.33	23	26
PTP1B/AKT1	0.011	0.037	-10000	0	-0.22	1	1
FYN	0.009	0.024	-10000	0	-0.5	1	1
p210 bcr-abl/PTP1B	0.006	0.041	-10000	0	-0.23	2	2
EGFR	-0.006	0.088	-10000	0	-0.51	14	14
EGF/EGFR	-0.049	0.09	-10000	0	-0.28	22	22
CSF1	0.004	0.052	-10000	0	-0.5	5	5
AKT1	0.01	0.001	-10000	0	-10000	0	0
INSR	0.01	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.02	0.095	-10000	0	-0.27	36	36
Insulin Receptor/Insulin	-0.006	0.021	-10000	0	-10000	0	0
HCK	-0.011	0.1	-10000	0	-0.5	19	19
CRK	0.01	0	-10000	0	-10000	0	0
TYK2	0.012	0.039	-10000	0	-10000	0	0
EGF	-0.089	0.2	-10000	0	-0.51	90	90
YES1	0.01	0	-10000	0	-10000	0	0
CAV1	-0.091	0.097	-10000	0	-0.25	70	70
TXN	0.006	0.034	-10000	0	-0.51	2	2
PTP1B/IRS1/GRB2	0.016	0.039	-10000	0	-0.3	1	1
cell migration	-0.006	0.041	0.23	2	-10000	0	2
STAT3	0.01	0.001	-10000	0	-10000	0	0
PRLR	-0.056	0.17	-10000	0	-0.51	59	59
ITGA2B	-0.042	0.15	-10000	0	-0.5	47	47
CSF1R	0.002	0.062	-10000	0	-0.5	7	7
Prolactin Receptor/Prolactin	-0.056	0.14	-10000	0	-0.37	70	70
FGR	-0.029	0.14	-10000	0	-0.5	36	36
PTP1B/p130 Cas	0.011	0.04	-10000	0	-0.25	2	2
Crk/p130 Cas	0.016	0.039	-10000	0	-0.26	1	1
DOK1	0.017	0.038	-10000	0	-0.25	1	1
JAK2	-0.005	0.063	-10000	0	-0.28	12	12
Jak2/Leptin Receptor/Leptin	-0.027	0.065	-10000	0	-0.41	4	4
PIK3R1	0.009	0.024	-10000	0	-0.5	1	1
PTPN1	0.006	0.041	-10000	0	-0.23	2	2
LYN	0.01	0	-10000	0	-10000	0	0
CDH2	-0.05	0.17	-10000	0	-0.51	54	54
SRC	0.015	0.018	-10000	0	-10000	0	0
ITGB3	-0.021	0.12	-10000	0	-0.51	27	27
CAT1/PTP1B	-0.029	0.13	-10000	0	-0.48	21	21
CAPN1	0.01	0.001	-10000	0	-10000	0	0
CSK	0.01	0	-10000	0	-10000	0	0
PI3K	-0.003	0.021	-10000	0	-10000	0	0
mol:H2O2	-0.001	0.002	-10000	0	-10000	0	0
STAT3 (dimer)	-0.022	0.064	-10000	0	-0.44	4	4
negative regulation of transcription	-0.004	0.062	-10000	0	-0.28	12	12
FCGR2A	0	0.07	-10000	0	-0.5	9	9
FER	0.008	0.004	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.056	0.13	-10000	0	-0.36	73	73
BLK	-0.071	0.19	-10000	0	-0.51	72	72
Insulin Receptor/Insulin/Shc	0	0	-10000	0	-10000	0	0
RHOA	0.01	0.001	-10000	0	-10000	0	0
LEPR	-0.037	0.15	-10000	0	-0.5	43	43
BCAR1	0.009	0.024	-10000	0	-0.5	1	1
p210 bcr-abl/Grb2	0.01	0	-10000	0	-10000	0	0
mol:NADPH	0	0.002	-10000	0	-10000	0	0
TRPV6	-0.037	0.14	-10000	0	-0.51	24	24
PRL	-0.011	0.085	-10000	0	-0.51	13	13
SOCS3	0	0.12	-10000	0	-1.2	4	4
SPRY2	0.007	0.024	-10000	0	-0.5	1	1
Insulin Receptor/Insulin/IRS1	-0.001	0.014	-10000	0	-0.3	1	1
CSF1/CSF1R	0.01	0.062	-10000	0	-0.36	6	6
Ras protein signal transduction	0.01	0.014	-10000	0	-10000	0	0
IRS1	0.009	0.024	-10000	0	-0.5	1	1
INS	0	0.001	-10000	0	-10000	0	0
LEP	-0.045	0.16	-10000	0	-0.51	48	48
STAT5B	0.004	0.044	-10000	0	-0.23	2	2
STAT5A	0.004	0.045	-10000	0	-0.23	3	3
GRB2	0.01	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.011	0.041	-10000	0	-0.26	2	2
CSN2	-0.015	0.045	-10000	0	-10000	0	0
PIK3CA	0.01	0	-10000	0	-10000	0	0
LAT	0.006	0.067	-10000	0	-0.45	9	9
YBX1	0.016	0.001	-10000	0	-10000	0	0
LCK	0.007	0.041	-10000	0	-0.5	3	3
SHC1	0.01	0	-10000	0	-10000	0	0
NOX4	-0.011	0.097	-10000	0	-0.51	17	17

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.01	0	-10000	0	-10000	0	0
HDAC4	0.009	0.024	-10000	0	-0.51	1	1
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.006	0.089	0.36	27	-10000	0	27
CDKN1A	-0.001	0.031	-10000	0	-0.68	1	1
KAT2B	0.01	0	-10000	0	-10000	0	0
BAX	0.01	0	-10000	0	-10000	0	0
FOXO3	0	0	-10000	0	-10000	0	0
FOXO1	0.01	0	-10000	0	-10000	0	0
FOXO4	0.018	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.01	0	-10000	0	-10000	0	0
TAT	-0.036	0.15	-10000	0	-0.51	41	41
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.007	0.03	-10000	0	-0.36	3	3
PPARGC1A	-0.12	0.22	-10000	0	-0.5	116	116
FHL2	-0.063	0.18	-10000	0	-0.51	65	65
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0	0.006	-10000	0	-10000	0	0
HIST2H4A	-0.006	0.089	-10000	0	-0.37	27	27
SIRT1/FOXO3a	0	0.006	-10000	0	-10000	0	0
SIRT1	0	0.009	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0	0.015	-10000	0	-0.3	1	1
SIRT1/Histone H1b	-0.01	0.034	-10000	0	-10000	0	0
apoptosis	0	0.006	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.074	0.13	-10000	0	-0.3	116	116
p53/SIRT1	0.001	0.017	0.38	1	-10000	0	1
SIRT1/FOXO4	0	0.007	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	-0.038	0.095	-10000	0	-0.27	65	65
HIST1H1E	0.003	0.046	-10000	0	-10000	0	0
SIRT1/p300	0	0.006	-10000	0	-10000	0	0
muscle cell differentiation	0.002	0.025	0.3	3	-10000	0	3
TP53	0	0.009	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0	0.006	-10000	0	-10000	0	0
CREBBP	0.01	0	-10000	0	-10000	0	0
MEF2D	0.01	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.032	0.1	-10000	0	-0.36	41	41
ACSS2	0.015	0.018	-10000	0	-0.36	1	1
SIRT1/PCAF/MYOD	-0.002	0.025	-10000	0	-0.3	3	3

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.008	0.055	-9999	-0.36	11	11
PDGFRB	0.008	0.024	-9999	-0.5	1	1
SPHK1	-0.009	0.021	-9999	-10000	0	0
mol:S1P	-0.011	0.027	-9999	-10000	0	0
S1P1/S1P/Gi	-0.015	0.14	-9999	-0.36	48	48
GNAO1	0.004	0.054	-9999	-0.51	5	5
PDGFB-D/PDGFRB/PLCgamma1	-0.007	0.13	-9999	-0.45	11	11
PLCG1	-0.009	0.13	-9999	-0.34	46	46
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.008	0.024	-9999	-0.5	1	1
GNAI2	0.01	0.004	-9999	-10000	0	0
GNAI3	0.01	0.003	-9999	-10000	0	0
GNAI1	0.008	0.034	-9999	-0.51	2	2
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.005	0.049	-9999	-0.31	11	11
S1P1/S1P	-0.02	0.053	-9999	-0.32	6	6
negative regulation of cAMP metabolic process	-0.014	0.13	-9999	-0.35	48	48
MAPK3	-0.025	0.18	-9999	-0.54	46	46
calcium-dependent phospholipase C activity	-0.001	0.003	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
KDR	-0.003	0.078	-9999	-0.5	11	11
PLCB2	0.009	0.071	-9999	-0.34	8	8
RAC1	0.01	0	-9999	-10000	0	0
RhoA/GTP	-0.017	0.045	-9999	-0.3	4	4
receptor internalization	-0.019	0.05	-9999	-0.3	6	6
PTGS2	-0.066	0.31	-9999	-0.98	46	46
Rac1/GTP	-0.017	0.045	-9999	-0.3	4	4
RHOA	0.01	0	-9999	-10000	0	0
VEGFA	0.009	0.003	-9999	-10000	0	0
negative regulation of T cell proliferation	-0.014	0.13	-9999	-0.35	48	48
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.035	0.14	-9999	-0.5	41	41
MAPK1	-0.025	0.18	-9999	-0.54	46	46
S1P1/S1P/PDGFB-D/PDGFRB	0.011	0.074	-9999	-0.34	6	6
ABCC1	0.01	0.002	-9999	-10000	0	0

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.002	0.02	0.2	2	-10000	0	2
RFC1	0.002	0.02	0.2	2	-10000	0	2
PRKDC	0.002	0.02	0.22	1	-10000	0	1
RIPK1	0.012	0.004	-10000	0	-10000	0	0
CASP7	-0.016	0.04	0.23	1	-0.5	1	2
FASLG/FAS/FADD/FAF1	0.006	0.074	0.21	33	-0.26	8	41
MAP2K4	-0.024	0.13	-10000	0	-0.46	7	7
mol:ceramide	-0.008	0.091	-10000	0	-0.37	10	10
GSN	0.002	0.02	0.2	2	-10000	0	2
FASLG/FAS/FADD/FAF1/Caspase 8	0.012	0.077	0.29	1	-0.33	8	9
FAS	0.004	0.048	-10000	0	-0.51	4	4
BID	0.001	0.021	0.28	1	-0.3	1	2
MAP3K1	-0.006	0.082	0.19	1	-0.29	7	8
MAP3K7	0.008	0.004	-10000	0	-10000	0	0
RB1	0.002	0.02	0.2	2	-0.2	1	3
CFLAR	0.012	0.004	-10000	0	-10000	0	0
HGF/MET	-0.064	0.14	-10000	0	-0.34	87	87
ARHGDIB	0.002	0.02	0.2	2	-0.2	1	3
FADD	0.008	0.004	-10000	0	-10000	0	0
actin filament polymerization	-0.002	0.02	-10000	0	-0.2	2	2
NFKB1	-0.046	0.084	-10000	0	-0.26	6	6
MAPK8	-0.055	0.2	-10000	0	-0.42	107	107
DFFA	0.002	0.02	0.2	2	-10000	0	2
DNA fragmentation during apoptosis	0.002	0.02	0.2	2	-0.2	1	3
FAS/FADD/MET	-0.021	0.076	-10000	0	-0.3	33	33
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	0.006	0.048	-10000	0	-0.51	4	4
FAF1	0.009	0.005	-10000	0	-10000	0	0
PARP1	0.002	0.02	0.2	2	-10000	0	2
DFFB	0.002	0.02	0.2	2	-0.2	1	3
CHUK	-0.041	0.074	-10000	0	-10000	0	0
FASLG	0.001	0.063	-10000	0	-0.51	7	7
FAS/FADD	-0.005	0.034	-10000	0	-0.37	4	4
HGF	-0.019	0.12	-10000	0	-0.5	26	26
LMNA	0.001	0.018	0.2	1	-10000	0	1
CASP6	0.002	0.02	0.2	2	-10000	0	2
CASP10	0.006	0.034	-10000	0	-0.51	2	2
CASP3	0.002	0.023	0.21	4	-0.23	1	5
PTPN13	-0.043	0.16	-10000	0	-0.5	48	48
CASP8	0.001	0.029	0.24	4	-0.37	1	5
IL6	-0.24	0.51	-10000	0	-1.2	106	106
MET	-0.022	0.12	-10000	0	-0.51	29	29
ICAD/CAD	0.002	0.019	0.2	1	-10000	0	1
FASLG/FAS/FADD/FAF1/Caspase 10	-0.008	0.092	-10000	0	-0.38	10	10
activation of caspase activity by cytochrome c	0.001	0.021	0.28	1	-0.3	1	2
PAK2	0.002	0.02	0.2	2	-10000	0	2
BCL2	0.007	0.041	-10000	0	-0.51	3	3

×

EPHB forward signaling

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
Ephrin A5/EPHB2	-0.039	0.11	-10000	0	-0.32	57	57
cell-cell adhesion	0.05	0.097	0.42	12	-10000	0	12
Ephrin B/EPHB2/RasGAP	-0.035	0.089	-10000	0	-0.49	2	2
ITSN1	0.01	0	-10000	0	-10000	0	0
PIK3CA	0.01	0	-10000	0	-10000	0	0
SHC1	0.01	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.009	0.05	-10000	0	-0.31	13	13
Ephrin B1/EPHB1	-0.037	0.1	-10000	0	-0.31	55	55
HRAS/GDP	-0.035	0.085	-10000	0	-0.37	11	11
Ephrin B/EPHB1/GRB7	-0.039	0.1	-10000	0	-0.54	6	6
Endophilin/SYNJ1	-0.007	0.093	-10000	0	-0.46	2	2
KRAS	0.01	0	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.035	0.095	-10000	0	-0.56	4	4
endothelial cell migration	-0.005	0.033	-10000	0	-10000	0	0
GRB2	0.01	0	-10000	0	-10000	0	0
GRB7	0.003	0.058	-10000	0	-0.51	6	6
PAK1	-0.003	0.097	-10000	0	-0.46	3	3
HRAS	0.01	0	-10000	0	-10000	0	0
RRAS	-0.009	0.099	-10000	0	-0.47	4	4
DNM1	0.003	0.059	-10000	0	-0.51	6	6
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.007	0.1	-10000	0	-0.53	4	4
lamellipodium assembly	-0.05	0.097	-10000	0	-0.42	12	12
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.007	0.07	-10000	0	-0.46	4	4
PIK3R1	0.009	0.024	-10000	0	-0.5	1	1
EPHB2	-0.049	0.17	-10000	0	-0.51	53	53
EPHB3	-0.001	0.076	-10000	0	-0.51	10	10
EPHB1	-0.049	0.17	-10000	0	-0.51	53	53
EPHB4	0.01	0	-10000	0	-10000	0	0
mol:GDP	-0.032	0.085	-10000	0	-0.4	9	9
Ephrin B/EPHB2	-0.036	0.091	-10000	0	-0.26	66	66
Ephrin B/EPHB3	-0.013	0.06	-10000	0	-0.5	2	2
JNK cascade	-0.032	0.12	-10000	0	-0.49	9	9
Ephrin B/EPHB1	-0.036	0.097	-10000	0	-0.27	63	63
RAP1/GDP	-0.026	0.073	-10000	0	-0.47	4	4
EFNB2	0.001	0.066	-10000	0	-0.5	8	8
EFNB3	0.005	0.048	-10000	0	-0.51	4	4
EFNB1	0.007	0.041	-10000	0	-0.5	3	3
Ephrin B2/EPHB1-2	-0.066	0.13	-10000	0	-0.3	104	104
RAP1B	0.01	0	-10000	0	-10000	0	0
RAP1A	0.01	0	-10000	0	-10000	0	0
CDC42/GTP	-0.049	0.098	-10000	0	-0.44	12	12
Rap1/GTP	-0.049	0.097	-10000	0	-0.42	12	12
axon guidance	-0.039	0.11	-10000	0	-0.32	57	57
MAPK3	0.019	0.063	-10000	0	-0.41	4	4
MAPK1	0.019	0.063	-10000	0	-0.41	4	4
Rac1/GDP	0.002	0.09	-10000	0	-0.49	4	4
actin cytoskeleton reorganization	-0.04	0.079	-10000	0	-0.35	12	12
CDC42/GDP	0.002	0.09	-10000	0	-0.49	4	4
PI3K	-0.005	0.033	-10000	0	-10000	0	0
EFNA5	0.002	0.063	-10000	0	-0.51	7	7
Ephrin B2/EPHB4	-0.005	0.039	-10000	0	-0.3	8	8
Ephrin B/EPHB2/Intersectin/N-WASP	0.005	0.065	-10000	0	-0.46	2	2
CDC42	0.01	0	-10000	0	-10000	0	0
RAS family/GTP	-0.048	0.095	-10000	0	-0.41	12	12
PTK2	0.015	0.028	-10000	0	-10000	0	0
MAP4K4	-0.032	0.13	-10000	0	-0.5	9	9
SRC	0.01	0	-10000	0	-10000	0	0
KALRN	0.007	0.041	-10000	0	-0.5	3	3
Intersectin/N-WASP	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.009	0.095	-10000	0	-0.38	5	5
MAP2K1	0.014	0.066	-10000	0	-0.43	4	4
WASL	0.01	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.062	0.12	-10000	0	-0.29	100	100
cell migration	0.019	0.07	-10000	0	-0.47	4	4
NRAS	0.01	0	-10000	0	-10000	0	0
SYNJ1	-0.008	0.095	-10000	0	-0.47	2	2
PXN	0.01	0	-10000	0	-10000	0	0
TF	-0.064	0.14	-10000	0	-0.47	19	19
HRAS/GTP	-0.053	0.1	-10000	0	-0.45	12	12
Ephrin B1/EPHB1-2	-0.063	0.13	-10000	0	-0.3	100	100
cell adhesion mediated by integrin	0.003	0.055	0.3	11	-10000	0	11
RAC1	0.01	0	-10000	0	-10000	0	0
mol:GTP	-0.058	0.11	-10000	0	-0.48	12	12
RAC1-CDC42/GTP	-0.053	0.1	-10000	0	-0.43	14	14
RASA1	0.01	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.026	0.073	-10000	0	-0.47	4	4
ruffle organization	-0.011	0.12	-10000	0	-0.42	12	12
NCK1	0.01	0	-10000	0	-10000	0	0
receptor internalization	-0.004	0.095	-10000	0	-0.44	3	3
Ephrin B/EPHB2/KALRN	-0.037	0.092	-10000	0	-0.49	3	3
ROCK1	0.012	0.048	-10000	0	-0.27	13	13
RAS family/GDP	-0.037	0.075	-10000	0	-0.34	11	11
Rac1/GTP	-0.052	0.1	-10000	0	-0.45	12	12
Ephrin B/EPHB1/Src/Paxillin	0.004	0.072	-10000	0	-0.31	12	12

×

Signaling events mediated by VEGFR1 and VEGFR2

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.021	0.084	-9999	-0.36	27	27
AKT1	0.028	0.12	-9999	-0.52	12	12
PTK2B	-0.011	0.14	-9999	-0.58	13	13
VEGFR2 homodimer/Frs2	-0.023	0.14	-9999	-0.71	11	11
CAV1	-0.31	0.25	-9999	-0.5	295	295
CALM1	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.042	0.12	-9999	-0.65	11	11
endothelial cell proliferation	0.034	0.12	-9999	-0.5	12	12
mol:Ca2+	0.003	0.12	-9999	-0.56	12	12
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.038	0.11	-9999	-0.6	11	11
RP11-342D11.1	-0.004	0.12	-9999	-0.57	12	12
CDH5	-0.059	0.17	-9999	-0.5	63	63
VEGFA homodimer	0	0	-9999	-10000	0	0
SHC1	0.01	0	-9999	-10000	0	0
SHC2	0	0.07	-9999	-0.5	9	9
HRAS/GDP	-0.03	0.09	-9999	-0.48	12	12
SH2D2A	0.009	0.024	-9999	-0.51	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.033	0.098	-9999	-0.5	14	14
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.042	0.12	-9999	-0.63	11	11
VEGFR1 homodimer	0.01	0	-9999	-10000	0	0
SHC/GRB2/SOS1	-0.034	0.099	-9999	-0.53	12	12
GRB10	0.003	0.12	-9999	-0.56	12	12
PTPN11	0.01	0	-9999	-10000	0	0
GRB2	0.01	0	-9999	-10000	0	0
PAK1	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.066	0.16	-9999	-0.55	35	35
HRAS	0.01	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	0.005	0.085	-9999	-0.35	12	12
HIF1A	0.01	0	-9999	-10000	0	0
FRS2	0.008	0.034	-9999	-0.51	2	2
oxygen and reactive oxygen species metabolic process	-0.037	0.11	-9999	-0.59	11	11
mol:GTP	0	0	-9999	-10000	0	0
FLT4	-0.004	0.084	-9999	-0.5	13	13
Nck/Pak	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.042	0.12	-9999	-0.63	11	11
mol:GDP	-0.033	0.097	-9999	-0.51	12	12
mol:NADP	0.023	0.11	-9999	-0.42	16	16
eNOS/Hsp90	0.027	0.1	-9999	-0.42	13	13
PIK3R1	0.009	0.024	-9999	-0.5	1	1
mol:IP3	0.003	0.12	-9999	-0.57	12	12
HIF1A/ARNT	0	0	-9999	-10000	0	0
SHB	0.009	0.024	-9999	-0.5	1	1
VEGFA	0.012	0	-9999	-10000	0	0
VEGFC	0.007	0.041	-9999	-0.5	3	3
FAK1/Vinculin	0.004	0.14	-9999	-0.6	13	13
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.051	0.12	-9999	-0.6	12	12
PTPN6	0.01	0	-9999	-10000	0	0
EPAS1	-0.049	0.17	-9999	-0.49	62	62
mol:L-citrulline	0.023	0.11	-9999	-0.42	16	16
ITGAV	0.01	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.039	0.11	-9999	-0.62	11	11
VEGFR2 homodimer/VEGFA homodimer	-0.041	0.12	-9999	-0.62	12	12
VEGFR2/3 heterodimer	-0.029	0.16	-9999	-0.69	16	16
VEGFB	0.01	0	-9999	-10000	0	0
MAPK11	0.003	0.13	-9999	-0.57	13	13
VEGFR2 homodimer	-0.03	0.16	-9999	-0.41	62	62
FLT1	0.01	0	-9999	-10000	0	0
NEDD4	0.01	0.024	-9999	-0.5	1	1
MAPK3	0.007	0.12	-9999	-0.54	12	12
MAPK1	0.007	0.12	-9999	-0.54	12	12
VEGFA145/NRP2	-0.002	0.028	-9999	-0.35	3	3
VEGFR1/2 heterodimer	-0.021	0.14	-9999	-0.68	11	11
KDR	-0.03	0.16	-9999	-0.42	62	62
VEGFA165/NRP1/VEGFR2 homodimer	-0.038	0.11	-9999	-0.57	13	13
SRC	0.01	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.008	0.12	-9999	-0.55	12	12
PI3K	-0.037	0.11	-9999	-0.57	13	13
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.041	0.12	-9999	-0.63	11	11
FES	0.002	0.12	-9999	-0.58	12	12
GAB1	-0.038	0.11	-9999	-0.58	12	12
VEGFR2 homodimer/VEGFA homodimer/Src	-0.041	0.12	-9999	-0.63	11	11
CTNNB1	0.01	0	-9999	-10000	0	0
SOS1	0.01	0	-9999	-10000	0	0
ARNT	0.01	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.11	0.14	-9999	-0.4	50	50
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.041	0.12	-9999	-0.63	11	11
PI3K/GAB1	0.028	0.12	-9999	-0.53	12	12
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.037	0.11	-9999	-0.59	11	11
PRKACA	0.01	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.05	0.14	-9999	-0.63	17	17
HSP90AA1	0.01	0	-9999	-10000	0	0
CDC42	0.002	0.12	-9999	-0.58	12	12
actin cytoskeleton reorganization	-0.041	0.12	-9999	-0.62	11	11
PTK2	-0.002	0.14	-9999	-0.65	13	13
EDG1	-0.004	0.12	-9999	-0.57	12	12
mol:DAG	0.003	0.12	-9999	-0.57	12	12
CaM/Ca2+	-0.034	0.099	-9999	-0.52	12	12
MAP2K3	0.009	0.12	-9999	-0.54	12	12
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.038	0.11	-9999	-0.58	12	12
PLCG1	0.002	0.12	-9999	-0.58	12	12
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.038	0.11	-9999	-0.58	12	12
IQGAP1	0.01	0	-9999	-10000	0	0
YES1	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.041	0.12	-9999	-0.63	11	11
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.041	0.12	-9999	-0.63	11	11
cell migration	0.01	0.14	-9999	-0.59	12	12
mol:PI-3-4-5-P3	-0.035	0.1	-9999	-0.53	13	13
FYN	0.009	0.024	-9999	-0.5	1	1
VEGFB/NRP1	-0.035	0.1	-9999	-0.53	12	12
mol:NO	0.023	0.11	-9999	-0.42	16	16
PXN	0.01	0	-9999	-10000	0	0
HRAS/GTP	-0.03	0.09	-9999	-0.48	12	12
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.001	0.12	-9999	-0.58	12	12
VHL	0.01	0	-9999	-10000	0	0
ITGB3	-0.02	0.12	-9999	-0.51	27	27
NOS3	0.022	0.12	-9999	-0.48	16	16
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.046	0.13	-9999	-0.64	14	14
RAC1	0.01	0	-9999	-10000	0	0
PRKCA	0.008	0.12	-9999	-0.53	12	12
PRKCB	0.003	0.13	-9999	-0.57	14	14
VCL	0.01	0	-9999	-10000	0	0
VEGFA165/NRP1	-0.004	0.12	-9999	-0.57	12	12
VEGFR1/2 heterodimer/VEGFA homodimer	-0.041	0.12	-9999	-0.63	11	11
VEGFA165/NRP2	-0.002	0.028	-9999	-0.35	3	3
MAPKKK cascade	-0.03	0.089	-9999	-0.48	12	12
NRP2	0.007	0.041	-9999	-0.5	3	3
VEGFC homodimer	0.007	0.041	-9999	-0.5	3	3
NCK1	0.01	0	-9999	-10000	0	0
ROCK1	0.01	0	-9999	-10000	0	0
FAK1/Paxillin	0.004	0.14	-9999	-0.6	13	13
MAP3K13	0.002	0.12	-9999	-0.58	12	12
PDPK1	0.025	0.11	-9999	-0.48	12	12

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.001	0.018	-9999	-0.26	2	2
NF kappa B1 p50/RelA/I kappa B alpha	-0.025	0.069	-9999	-0.36	3	3
AP1	-0.039	0.088	-9999	-0.45	4	4
mol:PIP3	-0.027	0.071	-9999	-0.41	3	3
AKT1	-0.002	0.015	-9999	-10000	0	0
PTK2B	0.018	0.032	-9999	-0.27	2	2
RHOA	0.024	0.025	-9999	-10000	0	0
PIK3CB	0.01	0	-9999	-10000	0	0
mol:Ca2+	0.005	0.085	-9999	-0.37	4	4
MAGI3	0.003	0.057	-9999	-0.5	6	6
RELA	0.01	0	-9999	-10000	0	0
apoptosis	-0.005	0.083	-9999	-0.25	44	44
HRAS/GDP	0	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.014	0.066	-9999	-0.26	8	8
NF kappa B1 p50/RelA	-0.025	0.07	-9999	-0.36	3	3
endothelial cell migration	0.021	0.021	-9999	-0.44	1	1
ADCY4	0.011	0.069	-9999	-0.36	5	5
ADCY5	-0.003	0.085	-9999	-0.3	18	18
ADCY6	0.019	0.052	-9999	-0.35	1	1
ADCY7	0.019	0.053	-9999	-0.35	1	1
ADCY1	0.017	0.058	-9999	-0.31	4	4
ADCY2	0.004	0.076	-9999	-0.3	11	11
ADCY3	0.02	0.052	-9999	-0.35	1	1
ADCY8	-0.054	0.1	-9999	-0.3	21	21
ADCY9	0.016	0.062	-9999	-0.33	5	5
GSK3B	0.024	0.03	-9999	-0.25	2	2
arachidonic acid secretion	0.023	0.05	-9999	-0.31	1	1
GNG2	0.007	0.033	-9999	-0.5	2	2
TRIP6	0.017	0.031	-9999	-0.36	3	3
GNAO1	0.019	0.034	-9999	-0.3	5	5
HRAS	0.01	0	-9999	-10000	0	0
NFKBIA	0.012	0.095	-9999	-0.42	3	3
GAB1	0.009	0.024	-9999	-0.5	1	1
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.022	0.14	-9999	-0.87	12	12
JUN	0.005	0.047	-9999	-0.5	4	4
LPA/LPA2/NHERF2	-0.004	0.033	-9999	-0.3	6	6
TIAM1	-0.026	0.16	-9999	-1	12	12
PIK3R1	0.008	0.024	-9999	-0.5	1	1
mol:IP3	0.004	0.086	-9999	-0.38	4	4
PLCB3	0.019	0.032	-9999	-0.26	6	6
FOS	-0.024	0.13	-9999	-0.5	31	31
positive regulation of mitosis	0.023	0.05	-9999	-0.31	1	1
LPA/LPA1-2-3	-0.028	0.08	-9999	-0.26	50	50
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.009	0.024	-9999	-0.5	1	1
stress fiber formation	0.017	0.051	-9999	-10000	0	0
GNAZ	-0.006	0.089	-9999	-0.29	41	41
EGFR/PI3K-beta/Gab1	-0.028	0.073	-9999	-0.43	3	3
positive regulation of dendritic cell cytokine production	-0.028	0.079	-9999	-0.26	50	50
LPA/LPA2/MAGI-3	-0.005	0.036	-9999	-0.3	7	7
ARHGEF1	0.03	0.015	-9999	-10000	0	0
GNAI2	0.022	0.01	-9999	-10000	0	0
GNAI3	0.022	0.01	-9999	-10000	0	0
GNAI1	0.021	0.023	-9999	-0.29	2	2
LPA/LPA3	-0.038	0.11	-9999	-0.36	49	49
LPA/LPA2	-0.001	0.017	-9999	-0.37	1	1
LPA/LPA1	-0.001	0.011	-9999	-0.24	1	1
HB-EGF/EGFR	-0.1	0.17	-9999	-0.32	169	169
HBEGF	-0.12	0.19	-9999	-0.37	164	164
mol:DAG	0.004	0.086	-9999	-0.38	4	4
cAMP biosynthetic process	0.006	0.062	-9999	-0.31	2	2
NFKB1	0.01	0	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
GNB1	0.01	0	-9999	-10000	0	0
LYN	0.012	0.095	-9999	-0.42	3	3
GNAQ	-0.01	0.087	-9999	-0.27	44	44
LPAR2	0.009	0.024	-9999	-0.51	1	1
LPAR3	-0.044	0.16	-9999	-0.5	49	49
LPAR1	0.013	0.007	-9999	-10000	0	0
IL8	-0.043	0.14	-9999	-0.4	25	25
PTK2	0.003	0.083	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.005	0.084	-9999	-0.25	44	44
EGFR	-0.006	0.088	-9999	-0.51	14	14
PLCG1	-0.008	0.097	-9999	-0.29	45	45
PLD2	0.003	0.083	-9999	-10000	0	0
G12/G13	0	0.007	-9999	-10000	0	0
PI3K-beta	-0.003	0.017	-9999	-10000	0	0
cell migration	-0.014	0.047	-9999	-0.25	12	12
SLC9A3R2	0.004	0.052	-9999	-0.5	5	5
PXN	0.017	0.052	-9999	-10000	0	0
HRAS/GTP	0.023	0.05	-9999	-0.32	1	1
RAC1	0.01	0	-9999	-10000	0	0
MMP9	-0.094	0.21	-9999	-0.51	93	93
PRKCE	0.004	0.053	-9999	-0.5	5	5
PRKCD	0.01	0.083	-9999	-0.39	3	3
Gi(beta/gamma)	0.021	0.053	-9999	-0.34	1	1
mol:LPA	0.003	0.007	-9999	-10000	0	0
TRIP6/p130 Cas/FAK1/Paxillin	-0.022	0.063	-9999	-10000	0	0
MAPKKK cascade	0.023	0.05	-9999	-0.31	1	1
contractile ring contraction involved in cytokinesis	0.024	0.024	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.018	0.099	-9999	-0.27	56	56
GNA15	-0.009	0.084	-9999	-0.26	44	44
GNA12	0.01	0	-9999	-10000	0	0
GNA13	0.01	0	-9999	-10000	0	0
MAPT	0.014	0.067	-9999	-0.27	8	8
GNA11	-0.01	0.09	-9999	-0.27	45	45
Rac1/GTP	-0.023	0.15	-9999	-0.93	12	12
MMP2	0.022	0.021	-9999	-0.44	1	1

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.015	0.085	-10000	0	-0.41	5	5
IKBKB	-0.001	0.048	-10000	0	-0.24	4	4
AKT1	-0.028	0.079	-10000	0	-0.26	4	4
IKBKG	0	0.05	-10000	0	-0.26	4	4
CALM1	-0.013	0.08	0.23	1	-0.59	5	6
PIK3CA	0.01	0	-10000	0	-10000	0	0
MAP3K1	-0.033	0.11	-10000	0	-0.56	4	4
MAP3K7	0.01	0	-10000	0	-10000	0	0
mol:Ca2+	-0.02	0.085	0.2	5	-0.64	5	10
DOK1	0.01	0	-10000	0	-10000	0	0
AP-1	-0.004	0.059	0.16	3	-0.25	6	9
LYN	0.01	0	-10000	0	-10000	0	0
BLNK	0.008	0.033	-10000	0	-0.5	2	2
SHC1	0.01	0	-10000	0	-10000	0	0
BCR complex	-0.072	0.16	-10000	0	-0.39	86	86
CD22	-0.049	0.11	-10000	0	-0.44	16	16
CAMK2G	-0.006	0.075	0.22	1	-0.54	5	6
CSNK2A1	0.01	0	-10000	0	-10000	0	0
INPP5D	0.007	0.041	-10000	0	-0.5	3	3
SHC/GRB2/SOS1	-0.043	0.096	-10000	0	-0.43	11	11
GO:0007205	-0.02	0.086	0.2	5	-0.65	5	10
SYK	0.007	0.041	-10000	0	-0.5	3	3
ELK1	-0.013	0.081	0.23	1	-0.6	5	6
NFATC1	-0.052	0.12	-10000	0	-0.4	15	15
B-cell antigen/BCR complex	-0.072	0.16	-10000	0	-0.39	86	86
PAG1/CSK	-0.001	0.016	-10000	0	-0.35	1	1
NFKBIB	0.007	0.019	-10000	0	-10000	0	0
HRAS	-0.011	0.079	0.21	1	-0.54	5	6
NFKBIA	0.007	0.018	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.011	0.016	-10000	0	-10000	0	0
RasGAP/Csk	-0.05	0.11	-10000	0	-0.5	9	9
mol:GDP	-0.02	0.084	0.24	1	-0.63	5	6
PTEN	0.01	0	-10000	0	-10000	0	0
CD79B	0	0.072	-10000	0	-0.51	9	9
NF-kappa-B/RelA/I kappa B alpha	0.011	0.016	-10000	0	-10000	0	0
GRB2	0.01	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.061	0.13	-10000	0	-0.41	14	14
PIK3R1	0.009	0.024	-10000	0	-0.5	1	1
mol:IP3	-0.025	0.086	0.2	5	-0.66	5	10
CSK	0.01	0	-10000	0	-10000	0	0
FOS	-0.022	0.097	0.23	1	-0.44	11	12
CHUK	0	0.05	-10000	0	-0.26	4	4
IBTK	0.01	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.032	0.077	-10000	0	-0.42	9	9
PTPN6	-0.045	0.099	-10000	0	-0.54	9	9
RELA	0.01	0	-10000	0	-10000	0	0
BCL2A1	0.01	0.02	-10000	0	-0.09	12	12
VAV2	-0.11	0.15	-10000	0	-0.36	86	86
ubiquitin-dependent protein catabolic process	0.01	0.018	-10000	0	-10000	0	0
BTK	-0.068	0.25	-10000	0	-1	30	30
CD19	-0.13	0.17	-10000	0	-0.42	84	84
MAP4K1	0.004	0.052	-10000	0	-0.5	5	5
CD72	0.008	0.033	-10000	0	-0.5	2	2
PAG1	0.009	0.024	-10000	0	-0.5	1	1
MAPK14	-0.022	0.1	-10000	0	-0.47	4	4
SH3BP5	0.003	0.057	-10000	0	-0.5	6	6
PIK3AP1	-0.014	0.1	0.21	4	-0.57	10	14
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.01	0.12	-10000	0	-0.84	6	6
RAF1	-0.004	0.075	0.21	1	-0.5	5	6
RasGAP/p62DOK/SHIP	-0.048	0.11	-10000	0	-0.48	10	10
CD79A	-0.085	0.2	-10000	0	-0.51	85	85
re-entry into mitotic cell cycle	-0.004	0.058	0.16	3	-0.25	6	9
RASA1	0.01	0	-10000	0	-10000	0	0
MAPK3	0.008	0.065	-10000	0	-0.41	5	5
MAPK1	0.008	0.065	0.2	1	-0.41	5	6
CD72/SHP1	-0.014	0.11	-10000	0	-0.52	9	9
NFKB1	0.01	0	-10000	0	-10000	0	0
MAPK8	-0.022	0.1	-10000	0	-0.47	4	4
actin cytoskeleton organization	-0.07	0.15	-10000	0	-0.32	85	85
NF-kappa-B/RelA	0.027	0.029	-10000	0	-10000	0	0
Calcineurin	-0.02	0.058	-10000	0	-0.48	5	5
PI3K	-0.094	0.12	-10000	0	-0.43	12	12
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.025	0.085	0.22	4	-0.68	5	9
SOS1	0.01	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.008	0.1	-10000	0	-0.69	6	6
DAPP1	-0.028	0.095	-10000	0	-0.85	4	4
cytokine secretion	-0.049	0.12	-10000	0	-0.37	15	15
mol:DAG	-0.025	0.086	0.2	5	-0.66	5	10
PLCG2	0.007	0.041	-10000	0	-0.5	3	3
MAP2K1	0.002	0.07	0.2	1	-0.46	5	6
B-cell antigen/BCR complex/FcgammaRIIB	-0.061	0.13	-10000	0	-0.33	86	86
mol:PI-3-4-5-P3	-0.072	0.09	-10000	0	-0.31	12	12
ETS1	0	0.071	0.22	1	-0.46	6	7
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.052	0.11	-10000	0	-0.5	11	11
B-cell antigen/BCR complex/LYN	-0.038	0.091	-10000	0	-0.42	10	10
MALT1	0.01	0	-10000	0	-10000	0	0
TRAF6	0.01	0	-10000	0	-10000	0	0
RAC1	-0.075	0.15	-10000	0	-0.34	85	85
B-cell antigen/BCR complex/LYN/SYK	-0.053	0.11	-10000	0	-0.42	17	17
CARD11	-0.029	0.1	0.23	1	-0.31	33	34
FCGR2B	0.009	0.024	-10000	0	-0.5	1	1
PPP3CA	0.01	0	-10000	0	-10000	0	0
BCL10	0.01	0	-10000	0	-10000	0	0
IKK complex	0.005	0.024	-10000	0	-0.092	2	2
PTPRC	-0.007	0.09	-10000	0	-0.5	15	15
PDPK1	-0.03	0.078	-10000	0	-0.25	4	4
PPP3CB	0.01	0	-10000	0	-10000	0	0
PPP3CC	0.01	0	-10000	0	-10000	0	0
POU2F2	0.012	0.012	-10000	0	-0.1	1	1

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	-0.18	0.25	-10000	0	-0.51	173	173
mol:Halofuginone	0.004	0	-10000	0	-10000	0	0
ITGA1	0.005	0.047	-10000	0	-0.5	4	4
CDKN1A	0.017	0.043	-10000	0	-0.61	1	1
PRL-3/alpha Tubulin	-0.001	0.017	-10000	0	-0.36	1	1
mol:Ca2+	-0.061	0.14	0.2	1	-0.38	77	78
AGT	-0.076	0.19	-10000	0	-0.51	77	77
CCNA2	-0.053	0.14	-10000	0	-0.49	15	15
TUBA1B	0.01	0	-10000	0	-10000	0	0
EGR1	-0.004	0.09	-10000	0	-0.35	30	30
CDK2/Cyclin E1	-0.073	0.14	-10000	0	-0.36	19	19
MAPK3	0.017	0.018	-10000	0	-0.36	1	1
PRL-2 /Rab GGTase beta	0	0	-10000	0	-10000	0	0
MAPK1	0.017	0.018	-10000	0	-0.36	1	1
PTP4A1	0.012	0.069	-10000	0	-10000	0	0
PTP4A3	0.009	0.024	-10000	0	-0.51	1	1
PTP4A2	0.01	0	-10000	0	-10000	0	0
ITGB1	0.017	0.018	-10000	0	-0.36	1	1
SRC	0.01	0	-10000	0	-10000	0	0
RAC1	0.018	0.033	-10000	0	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0	0	-10000	0	-10000	0	0
PRL-1/ATF-5	0.015	0.065	-10000	0	-10000	0	0
RABGGTA	0.01	0	-10000	0	-10000	0	0
BCAR1	0	0.019	0.2	1	-0.37	1	2
RHOC	0.018	0.033	-10000	0	-10000	0	0
RHOA	0.018	0.033	-10000	0	-10000	0	0
cell motility	0.021	0.035	-10000	0	-10000	0	0
PRL-1/alpha Tubulin	0.016	0.064	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	-0.004	0.037	-10000	0	-0.36	5	5
ROCK1	0.021	0.035	-10000	0	-10000	0	0
RABGGTB	0.01	0	-10000	0	-10000	0	0
CDK2	0.01	0	-10000	0	-10000	0	0
mitosis	0.012	0.069	-10000	0	-10000	0	0
ATF5	0.009	0.024	-10000	0	-0.51	1	1

×

Lissencephaly gene (LIS1) in neuronal migration and development

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.01	0	-9999	-10000	0	0
VLDLR	-0.001	0.074	-9999	-0.5	10	10
LRPAP1	0.01	0	-9999	-10000	0	0
NUDC	0.01	0	-9999	-10000	0	0
RELN/LRP8	-0.051	0.11	-9999	-0.29	82	82
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0.01	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.023	0.11	-9999	-0.27	17	17
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	-0.003	0.067	-9999	-0.51	8	8
IQGAP1	0.01	0	-9999	-10000	0	0
PLA2G7	-0.001	0.075	-9999	-0.51	10	10
CALM1	0.01	0	-9999	-10000	0	0
DYNLT1	0.01	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.009	0.055	-9999	-0.36	11	11
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.01	0	-9999	-10000	0	0
CDK5R1	-0.006	0.089	-9999	-0.51	14	14
LIS1/Poliovirus Protein 3A	0	0	-9999	-10000	0	0
CDK5R2	-0.14	0.23	-9999	-0.51	129	129
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.056	0.13	-9999	-0.32	81	81
YWHAE	0.01	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.037	0.11	-9999	-0.33	27	27
MAP1B	-0.002	0.02	-9999	-0.28	1	1
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.016	0.1	-9999	-0.47	1	1
RELN	-0.068	0.18	-9999	-0.5	71	71
PAFAH/LIS1	0.014	0.046	-9999	-0.3	10	10
LIS1/CLIP170	0.021	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.047	0.071	-9999	-0.33	1	1
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.019	0.11	-9999	-0.42	11	11
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.045	0.12	-9999	-0.35	27	27
LIS1/IQGAP1	0.021	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.018	0	-9999	-10000	0	0
PAFAH1B3	-0.015	0.11	-9999	-0.51	22	22
PAFAH1B2	0.01	0	-9999	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0.018	0.015	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.061	0.088	-9999	-0.4	1	1
LRP8	-0.002	0.079	-9999	-0.51	11	11
NDEL1/Katanin 60	-0.037	0.11	-9999	-0.33	27	27
P39/CDK5	-0.082	0.16	-9999	-0.47	27	27
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.021	0	-9999	-10000	0	0
CDK5	-0.015	0.1	-9999	-10000	0	0
PPP2R5D	0.01	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0	-9999	-10000	0	0
CSNK2A1	0.01	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.046	0.1	-9999	-0.5	8	8
RELN/VLDLR	-0.051	0.11	-9999	-0.52	5	5
CDC42	0	0	-9999	-10000	0	0

×

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

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
MET/RANBP9	-0.022	0.086	-9999	-0.36	29	29
CRKL	0.008	0.072	-9999	-0.35	4	4
mol:PIP3	-0.016	0.005	-9999	-10000	0	0
AKT1	0.001	0.004	-9999	-10000	0	0
PTK2B	0.008	0.033	-9999	-0.5	2	2
RAPGEF1	0.014	0.069	-9999	-0.33	4	4
RANBP10	0.01	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
HGF/MET/SHIP2	-0.035	0.1	-9999	-0.31	52	52
MAP3K5	0.019	0.073	-9999	-0.37	5	5
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.031	0.089	-9999	-0.31	19	19
AP1	-0.029	0.086	-9999	-0.32	35	35
mol:SU11274	0	0	-9999	-10000	0	0
SHC1	0.01	0	-9999	-10000	0	0
apoptosis	-0.041	0.19	-9999	-0.7	35	35
STAT3 (dimer)	0.008	0.077	-9999	-0.39	4	4
GAB1/CRKL/SHP2/PI3K	-0.017	0.056	-9999	-0.37	3	3
INPP5D	0.007	0.041	-9999	-0.5	3	3
CBL/CRK	0.013	0.069	-9999	-0.33	4	4
PTPN11	0.01	0	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
PLCG1	0.01	0	-9999	-10000	0	0
PTEN	0.01	0	-9999	-10000	0	0
ELK1	-0.01	0.046	-9999	-0.19	29	29
mol:SU5416	0	0	-9999	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.014	0.041	-9999	-0.25	3	3
PAK1	0.007	0.004	-9999	-10000	0	0
HGF/MET/RANBP10	-0.035	0.1	-9999	-0.31	52	52
HRAS	-0.006	0.12	-9999	-0.56	17	17
DOCK1	0.014	0.069	-9999	-0.33	4	4
GAB1	0.002	0.076	-9999	-0.28	19	19
CRK	0.008	0.072	-9999	-0.33	5	5
mol:PHA665752	0	0	-9999	-10000	0	0
mol:GDP	-0.041	0.13	-9999	-0.49	36	36
JUN	0.005	0.047	-9999	-0.5	4	4
EntrezGene:200958	0	0	-9999	-10000	0	0
HGF/MET	-0.022	0.065	-9999	-0.22	36	36
PIK3R1	0.009	0.024	-9999	-0.5	1	1
cell morphogenesis	0.029	0.082	-9999	-0.42	3	3
GRB2/SHC	0.003	0.061	-9999	-0.23	17	17
FOS	-0.024	0.13	-9999	-0.5	31	31
GLMN	0	0	-9999	-10000	0	0
cell motility	-0.01	0.046	-9999	-0.19	29	29
HGF/MET/MUC20	-0.035	0.1	-9999	-0.32	52	52
cell migration	-0.018	0.054	-9999	-0.22	17	17
GRB2	0.01	0	-9999	-10000	0	0
CBL	0.01	0	-9999	-10000	0	0
MET/RANBP10	-0.022	0.086	-9999	-0.36	29	29
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.003	0.079	-9999	-0.41	4	4
MET/MUC20	-0.023	0.088	-9999	-0.37	29	29
RAP1B	0.019	0.066	-9999	-0.36	2	2
RAP1A	0.019	0.066	-9999	-0.36	2	2
HGF/MET/RANBP9	-0.035	0.1	-9999	-0.31	52	52
RAF1	0.001	0.12	-9999	-0.52	17	17
STAT3	0.008	0.078	-9999	-0.4	4	4
cell proliferation	0.011	0.1	-9999	-0.33	36	36
RPS6KB1	0.002	0.027	-9999	-0.15	1	1
MAPK3	-0.013	0.042	-9999	-10000	0	0
MAPK1	-0.013	0.042	-9999	-10000	0	0
RANBP9	0.01	0	-9999	-10000	0	0
MAPK8	0.032	0.063	-9999	-0.32	2	2
SRC	0.01	0.074	-9999	-0.38	4	4
PI3K	0.002	0.063	-9999	-0.34	4	4
MET/Glomulin	-0.011	0.079	-9999	-0.32	29	29
SOS1	0.01	0	-9999	-10000	0	0
MAP2K1	0.007	0.11	-9999	-0.48	17	17
MET	-0.022	0.12	-9999	-0.51	29	29
MAP4K1	0.013	0.077	-9999	-0.36	7	7
PTK2	0.01	0	-9999	-10000	0	0
MAP2K2	0.007	0.11	-9999	-0.48	17	17
BAD	0.007	0.004	-9999	-10000	0	0
MAP2K4	0.024	0.069	-9999	-0.35	4	4
SHP2/GRB2/SOS1/GAB1	-0.023	0.071	-9999	-0.32	18	18
INPPL1	0.01	0	-9999	-10000	0	0
PXN	0.01	0	-9999	-10000	0	0
SH3KBP1	0.01	0	-9999	-10000	0	0
HGS	-0.003	0.064	-9999	-0.24	17	17
PLCgamma1/PKC	0	0	-9999	-10000	0	0
HGF	-0.019	0.12	-9999	-0.5	26	26
RASA1	0.01	0	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
PTPRJ	0.01	0	-9999	-10000	0	0
NCK/PLCgamma1	0.003	0.064	-9999	-0.23	17	17
PDPK1	-0.007	0.004	-9999	-10000	0	0
HGF/MET/SHIP	-0.036	0.11	-9999	-0.33	52	52

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.019	0.084	-10000	0	-0.53	10	10
FYN	0.03	0.13	-10000	0	-0.65	13	13
LAT/GRAP2/SLP76	-0.016	0.11	-10000	0	-0.57	13	13
IKBKB	0.01	0	-10000	0	-10000	0	0
AKT1	0.037	0.095	-10000	0	-0.43	13	13
B2M	0.011	0.003	-10000	0	-10000	0	0
IKBKG	-0.008	0.024	-10000	0	-0.14	6	6
MAP3K8	0.008	0.033	-10000	0	-0.5	2	2
mol:Ca2+	-0.01	0.024	-10000	0	-0.11	12	12
integrin-mediated signaling pathway	-0.001	0.019	-10000	0	-0.3	2	2
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.034	0.14	-10000	0	-0.66	13	13
TRPV6	-0.073	0.18	-10000	0	-0.51	67	67
CD28	0.009	0.024	-10000	0	-0.51	1	1
SHC1	0.03	0.12	-10000	0	-0.62	12	12
receptor internalization	0.022	0.13	-10000	0	-0.61	13	13
PRF1	-0.016	0.26	-10000	0	-1.1	24	24
KRAS	0.01	0	-10000	0	-10000	0	0
GRB2	0.01	0	-10000	0	-10000	0	0
COT/AKT1	0.038	0.08	-10000	0	-0.35	13	13
LAT	0.03	0.12	-10000	0	-0.69	10	10
EntrezGene:6955	0	0.005	-10000	0	-10000	0	0
CD3D	0.008	0.042	-10000	0	-0.51	3	3
CD3E	0.005	0.054	-10000	0	-0.52	5	5
CD3G	0	0.075	-10000	0	-0.51	10	10
RASGRP2	0.002	0.041	-10000	0	-0.16	25	25
RASGRP1	0.036	0.1	-10000	0	-0.43	15	15
HLA-A	0.011	0.003	-10000	0	-10000	0	0
RASSF5	0.008	0.033	-10000	0	-0.5	2	2
RAP1A/GTP/RAPL	-0.001	0.019	-10000	0	-0.3	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.029	0.037	-10000	0	-0.12	12	12
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.015	0.042	-10000	0	-0.23	9	9
PRKCA	-0.005	0.053	-10000	0	-0.27	10	10
GRAP2	-0.005	0.087	-10000	0	-0.5	14	14
mol:IP3	0.01	0.11	0.21	58	-0.44	11	69
EntrezGene:6957	0.001	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	0.015	0.11	-10000	0	-0.62	10	10
ORAI1	0.042	0.099	0.28	67	-10000	0	67
CSK	0.029	0.12	-10000	0	-0.7	10	10
B7 family/CD28	-0.034	0.14	-10000	0	-0.69	16	16
CHUK	0.01	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	0.023	0.14	-10000	0	-0.74	12	12
PTPN6	0.027	0.12	-10000	0	-0.7	10	10
VAV1	0.028	0.13	-10000	0	-0.64	13	13
Monovalent TCR/CD3	0.007	0.09	-10000	0	-0.38	17	17
CBL	0.01	0	-10000	0	-10000	0	0
LCK	0.027	0.13	-10000	0	-0.69	12	12
PAG1	0.029	0.12	-10000	0	-0.7	10	10
RAP1A	0.01	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	0.022	0.14	-10000	0	-0.73	12	12
CD80	-0.002	0.078	-10000	0	-0.5	11	11
CD86	0	0.071	-10000	0	-0.51	9	9
PDK1/CARD11/BCL10/MALT1	-0.018	0.051	-10000	0	-0.28	9	9
HRAS	0.01	0	-10000	0	-10000	0	0
GO:0035030	0.024	0.13	-10000	0	-0.56	16	16
CD8A	0.004	0.058	-10000	0	-0.51	6	6
CD8B	0.003	0.064	-10000	0	-0.51	7	7
PTPRC	-0.006	0.091	-10000	0	-0.5	15	15
PDK1/PKC theta	0.032	0.12	-10000	0	-0.47	19	19
CSK/PAG1	0.032	0.12	-10000	0	-0.66	10	10
SOS1	0.01	0	-10000	0	-10000	0	0
peptide-MHC class I	0.016	0.007	-10000	0	-10000	0	0
GRAP2/SLP76	-0.02	0.13	-10000	0	-0.59	17	17
STIM1	0.021	0.049	-10000	0	-10000	0	0
RAS family/GTP	0.038	0.042	-10000	0	-0.18	6	6
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	0.021	0.14	-10000	0	-0.66	13	13
mol:DAG	-0.006	0.077	-10000	0	-0.37	13	13
RAP1A/GDP	0.014	0.016	-10000	0	-0.062	3	3
PLCG1	0.01	0	-10000	0	-10000	0	0
CD247	0.004	0.058	-10000	0	-0.51	6	6
cytotoxic T cell degranulation	-0.013	0.24	-10000	0	-1	24	24
RAP1A/GTP	-0.004	0.013	-10000	0	-0.064	10	10
mol:PI-3-4-5-P3	0.036	0.11	-10000	0	-0.52	13	13
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.006	0.13	0.23	58	-0.56	12	70
NRAS	0.01	0	-10000	0	-10000	0	0
ZAP70	0.003	0.058	-10000	0	-0.5	6	6
GRB2/SOS1	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.015	0.1	-10000	0	-0.55	13	13
MALT1	0.01	0	-10000	0	-10000	0	0
TRAF6	0.01	0	-10000	0	-10000	0	0
CD8 heterodimer	0.006	0.071	-10000	0	-0.46	10	10
CARD11	-0.023	0.13	-10000	0	-0.51	29	29
PRKCB	-0.008	0.067	-10000	0	-0.31	17	17
PRKCE	-0.006	0.055	-10000	0	-0.28	11	11
PRKCQ	0.024	0.14	-10000	0	-0.52	21	21
LCP2	0.007	0.041	-10000	0	-0.5	3	3
BCL10	0.01	0	-10000	0	-10000	0	0
regulation of survival gene product expression	0.037	0.082	-10000	0	-0.36	13	13
IKK complex	0.037	0.034	-10000	0	-0.11	9	9
RAS family/GDP	-0.001	0.005	-10000	0	-10000	0	0
MAP3K14	0.039	0.062	-10000	0	-0.29	10	10
PDPK1	0.039	0.091	-10000	0	-0.42	12	12
TCR/CD3/MHC I/CD8/Fyn	0.021	0.14	-10000	0	-0.77	10	10

×

BARD1 signaling events

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
BARD1/CSTF1	-0.002	0.028	-10000	0	-0.36	3	3
ATM	0.01	0	-10000	0	-10000	0	0
UBE2D3	0.01	0	-10000	0	-10000	0	0
PRKDC	0.01	0	-10000	0	-10000	0	0
ATR	0.01	0	-10000	0	-10000	0	0
UBE2L3	0.01	0	-10000	0	-10000	0	0
FANCD2	0.019	0.013	-10000	0	-10000	0	0
protein ubiquitination	-0.092	0.12	-10000	0	-0.5	3	3
XRCC5	0.01	0	-10000	0	-10000	0	0
XRCC6	0.01	0	-10000	0	-10000	0	0
M/R/N Complex	0	0	-10000	0	-10000	0	0
MRE11A	0.01	0	-10000	0	-10000	0	0
DNA-PK	0	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	-0.006	0.02	-10000	0	-10000	0	0
FANCF	0.01	0	-10000	0	-10000	0	0
BRCA1	0.008	0.034	-10000	0	-0.51	2	2
CCNE1	-0.18	0.25	-10000	0	-0.51	173	173
CDK2/Cyclin E1	-0.14	0.18	-10000	0	-0.36	173	173
FANCG	0.01	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	-0.004	0.037	-10000	0	-0.36	5	5
FANCE	0.01	0	-10000	0	-10000	0	0
FANCC	0.01	0	-10000	0	-10000	0	0
NBN	0.01	0	-10000	0	-10000	0	0
FANCA	-0.01	0.1	-10000	0	-0.51	18	18
DNA repair	-0.018	0.12	-10000	0	-0.46	6	6
BRCA1/BARD1/ubiquitin	-0.004	0.037	-10000	0	-0.36	5	5
BARD1/DNA-PK	-0.002	0.021	-10000	0	-0.27	1	1
FANCL	0.01	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.002	0.028	0.36	3	-10000	0	3
BRCA1/BARD1/CTIP/M/R/N Complex	0.03	0.019	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1/TopBP1	-0.003	0.031	-10000	0	-0.3	5	5
BRCA1/BARD1/P53	-0.003	0.027	-10000	0	-0.26	5	5
BARD1/CSTF1/BRCA1	-0.003	0.031	-10000	0	-0.3	5	5
BRCA1/BACH1	0.008	0.034	-10000	0	-0.51	2	2
BARD1	0.007	0.041	-10000	0	-0.5	3	3
PCNA	0.008	0.034	-10000	0	-0.51	2	2
BRCA1/BARD1/UbcH5C	-0.003	0.031	-10000	0	-0.3	5	5
BRCA1/BARD1/UbcH7	-0.003	0.031	-10000	0	-0.3	5	5
BRCA1/BARD1/RAD51/PCNA	-0.053	0.11	-10000	0	-0.28	88	88
BARD1/DNA-PK/P53	-0.002	0.019	-10000	0	-10000	0	0
BRCA1/BARD1/Ubiquitin	-0.004	0.037	-10000	0	-0.36	5	5
BRCA1/BARD1/CTIP	-0.003	0.027	-10000	0	-10000	0	0
FA complex	0.026	0.029	-10000	0	-10000	0	0
BARD1/EWS	-0.002	0.028	-10000	0	-0.36	3	3
RBBP8	0.018	0	-10000	0	-10000	0	0
TP53	0.01	0	-10000	0	-10000	0	0
TOPBP1	0.01	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.003	0.027	0.26	5	-10000	0	5
BRCA1/BARD1	-0.093	0.12	-10000	0	-0.5	3	3
CSTF1	0.01	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.002	0.029	-10000	0	-0.36	3	3
CDK2	0.01	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.086	0.2	-10000	0	-0.51	86	86
RAD50	0.01	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.004	0.037	-10000	0	-0.36	5	5
EWSR1	0.01	0	-10000	0	-10000	0	0

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.01	0.057	-9999	-0.33	14	14
EFNA5	0.002	0.063	-9999	-0.51	7	7
FYN	0.008	0.055	-9999	-0.29	15	15
neuron projection morphogenesis	-0.01	0.057	-9999	-0.33	14	14
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.01	0.057	-9999	-0.33	14	14
EPHA5	-0.003	0.068	-9999	-0.51	8	8

×

IL1-mediated signaling events

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
UBC13/UEV1A	-0.001	0.017	-10000	0	-0.36	1	1
PRKCZ	0.007	0.041	-10000	0	-0.5	3	3
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.01	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.01	0.038	-10000	0	-0.26	2	2
IRAK/TOLLIP	0.021	0.019	-10000	0	-0.27	1	1
IKBKB	0.01	0	-10000	0	-10000	0	0
IKBKG	0.01	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.12	0.17	-10000	0	-0.36	155	155
IL1A	-0.14	0.23	-10000	0	-0.5	138	138
IL1B	-0.006	0.091	-10000	0	-0.35	30	30
IRAK/TRAF6/p62/Atypical PKCs	-0.003	0.024	-10000	0	-10000	0	0
IL1R2	-0.012	0.1	-10000	0	-0.51	20	20
IL1R1	0.007	0.041	-10000	0	-0.5	3	3
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.012	0.051	0.19	9	-0.38	2	11
TOLLIP	0.01	0	-10000	0	-10000	0	0
TICAM2	0.007	0.041	-10000	0	-0.5	3	3
MAP3K3	0.009	0.024	-10000	0	-0.5	1	1
TAK1/TAB1/TAB2	0	0	-10000	0	-10000	0	0
IKK complex/ELKS	0.049	0.017	-10000	0	-10000	0	0
JUN	0.024	0.053	-10000	0	-0.43	1	1
MAP3K7	0.01	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.016	0.061	-10000	0	-0.47	2	2
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.078	0.12	-10000	0	-0.52	2	2
PIK3R1	0.009	0.024	-10000	0	-0.5	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.071	0.11	-10000	0	-0.49	2	2
IL1 beta fragment/IL1R1/IL1RAP	-0.018	0.07	-10000	0	-0.52	2	2
NFKB1	0.01	0	-10000	0	-10000	0	0
MAPK8	0.021	0.048	-10000	0	-10000	0	0
IRAK1	0.016	0.021	-10000	0	-0.3	2	2
IL1RN/IL1R1	-0.008	0.051	-10000	0	-0.35	10	10
IRAK4	0.01	0	-10000	0	-10000	0	0
PRKCI	0.01	0	-10000	0	-10000	0	0
TRAF6	0.01	0	-10000	0	-10000	0	0
PI3K	-0.001	0.016	-10000	0	-0.35	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.019	0.053	-10000	0	-0.39	2	2
CHUK	0.01	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.018	0.07	-10000	0	-0.52	2	2
IL1 beta/IL1R2	-0.031	0.097	-10000	0	-0.31	47	47
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.001	0.015	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.014	0.054	-10000	0	-0.42	2	2
IRAK3	-0.003	0.081	-10000	0	-0.5	12	12
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.017	0.063	-10000	0	-0.47	2	2
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.046	0.12	-10000	0	-0.46	2	2
IL1 alpha/IL1R1/IL1RAP	-0.088	0.14	-10000	0	-0.3	139	139
RELA	0.01	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.009	0.024	-10000	0	-0.51	1	1
MYD88	0.01	0	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0.013	0.024	-10000	0	-10000	0	0
IL1RAP	0.01	0	-10000	0	-10000	0	0
UBE2N	0.01	0	-10000	0	-10000	0	0
IRAK/TRAF6	-0.014	0.052	-10000	0	-0.39	2	2
CASP1	0.005	0.047	-10000	0	-0.5	4	4
IL1RN/IL1R2	-0.021	0.086	-10000	0	-0.37	26	26
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.017	0.065	-10000	0	-0.49	2	2
TMEM189-UBE2V1	0.003	0.024	-10000	0	-0.51	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.039	0.092	-10000	0	-0.42	3	3
PIK3CA	0.01	0	-10000	0	-10000	0	0
IL1RN	0.002	0.062	-10000	0	-0.5	7	7
TRAF6/TAK1/TAB1/TAB2	-0.001	0.011	-10000	0	-10000	0	0
MAP2K6	0.016	0.051	-10000	0	-10000	0	0

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.03	0.074	0.4	5	-10000	0	5
GNAI2	0.01	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.02	0.074	-10000	0	-0.3	31	31
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.004	0.053	-10000	0	-0.51	5	5
RhoA/GTP	-0.03	0.075	-10000	0	-0.41	5	5
negative regulation of cAMP metabolic process	-0.011	0.093	-10000	0	-0.26	33	33
GNAZ	-0.035	0.14	-10000	0	-0.5	41	41
GNAI3	0.01	0	-10000	0	-10000	0	0
GNA12	0.01	0	-10000	0	-10000	0	0
S1PR5	-0.024	0.13	-10000	0	-0.5	31	31
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.011	0.094	-10000	0	-0.26	33	33
RhoA/GDP	0	0	-10000	0	-10000	0	0
RHOA	0.01	0	-10000	0	-10000	0	0
GNAI1	0.008	0.033	-10000	0	-0.5	2	2

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.009	0.04	-9999	-0.32	4	4
NFATC2	-0.002	0.07	-9999	-0.31	20	20
NFATC3	0.012	0.025	-9999	-10000	0	0
CD40LG	-0.034	0.22	-9999	-0.71	23	23
PTGS2	-0.049	0.24	-9999	-0.66	34	34
JUNB	0.007	0.041	-9999	-0.5	3	3
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.005	0.009	-9999	-10000	0	0
CaM/Ca2+	-0.005	0.009	-9999	-10000	0	0
CALM1	0.009	0.007	-9999	-10000	0	0
JUN	0.005	0.048	-9999	-0.5	4	4
mol:Ca2+	-0.005	0.01	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0.002	-9999	-10000	0	0
FOSL1	-0.017	0.12	-9999	-0.51	24	24
CREM	0.01	0	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.049	0.096	-9999	-0.64	5	5
FOS	-0.025	0.13	-9999	-0.51	31	31
IFNG	-0.042	0.23	-9999	-0.65	36	36
AP-1/NFAT1-c-4	-0.1	0.19	-9999	-0.74	21	21
FASLG	-0.026	0.21	-9999	-0.66	21	21
NFAT1-c-4/ICER1	-0.031	0.071	-9999	-0.4	9	9
IL2RA	-0.039	0.22	-9999	-0.62	32	32
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	-0.042	0.23	-9999	-0.71	26	26
JunB/Fra1/NFAT1-c-4	-0.041	0.088	-9999	-0.43	10	10
IL4	-0.027	0.2	-9999	-0.62	20	20
IL2	-0.001	0.01	-9999	-10000	0	0
IL3	-0.01	0.016	-9999	-10000	0	0
FKBP1A	0.01	0	-9999	-10000	0	0
BATF3	0.009	0.024	-9999	-0.51	1	1
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.01	0.001	-9999	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	-0.001	0.014	-9999	-0.3	1	1
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.01	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.01	0.1	-9999	-0.51	18	18
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.01	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.006	0.042	-9999	-0.2	4	4
response to UV	0	0	-9999	-10000	0	0
YES1	0.01	0	-9999	-10000	0	0
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.009	0.024	-9999	-0.5	1	1
FYN	0.009	0.024	-9999	-0.5	1	1
MAP3K12	0.01	0	-9999	-10000	0	0
FGR	-0.029	0.14	-9999	-0.5	36	36
p38 alpha/TAB1	-0.015	0.051	-9999	-0.29	9	9
PRKG1	-0.046	0.16	-9999	-0.5	51	51
DUSP8	-0.002	0.077	-9999	-0.5	11	11
PGK/cGMP/p38 alpha	-0.036	0.094	-9999	-0.36	24	24
apoptosis	-0.015	0.049	-9999	-0.28	9	9
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0.01	0	-9999	-10000	0	0
DUSP1	-0.041	0.15	-9999	-0.5	47	47
PAK1	0.01	0	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.001	0.012	-9999	-10000	0	0
TRAF6	0.01	0	-9999	-10000	0	0
RAC1	0.01	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	0.01	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.009	0.094	-9999	-0.37	17	17
BLK	-0.071	0.19	-9999	-0.51	72	72
HCK	-0.011	0.1	-9999	-0.5	19	19
MAP2K3	0.01	0	-9999	-10000	0	0
DUSP16	0.01	0	-9999	-10000	0	0
DUSP10	0.008	0.033	-9999	-0.5	2	2
TRAF6/MEKK3	-0.001	0.013	-9999	-0.27	1	1
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.017	0.068	-9999	-0.31	9	9
positive regulation of innate immune response	0.014	0.099	-9999	-0.4	16	16
LCK	0.007	0.041	-9999	-0.5	3	3
p38alpha-beta/MKP7	0.019	0.095	-9999	-0.43	10	10
p38alpha-beta/MKP5	0.018	0.099	-9999	-0.45	11	11
PGK/cGMP	-0.039	0.11	-9999	-0.36	51	51
PAK2	0.01	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.003	0.12	-9999	-0.46	15	15
CDC42	0.01	0	-9999	-10000	0	0
RALB	0.01	0	-9999	-10000	0	0
RALA	0.01	0	-9999	-10000	0	0
PAK3	-0.056	0.17	-9999	-0.51	58	58

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.006	0.047	-9999	-0.5	4	4
ELF1	0	0.058	-9999	-0.33	1	1
CCNA2	-0.12	0.23	-9999	-0.51	119	119
PIK3CA	0.01	0	-9999	-10000	0	0
JAK3	0.01	0	-9999	-10000	0	0
PIK3R1	0.009	0.024	-9999	-0.5	1	1
JAK1	0.01	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.051	0.048	-9999	-0.51	1	1
SHC1	0.01	0	-9999	-10000	0	0
SP1	0.01	0.047	-9999	-0.33	9	9
IL2RA	-0.005	0.11	-9999	-0.4	34	34
IL2RB	0.008	0.033	-9999	-0.5	2	2
SOS1	0.01	0	-9999	-10000	0	0
IL2RG	0.005	0.052	-9999	-0.5	5	5
G1/S transition of mitotic cell cycle	-0.018	0.12	-9999	-0.68	10	10
PTPN11	0.01	0	-9999	-10000	0	0
CCND2	0.01	0.1	-9999	-0.73	9	9
LCK	0.007	0.041	-9999	-0.5	3	3
GRB2	0.01	0	-9999	-10000	0	0
IL2	0.006	0.005	-9999	-10000	0	0
CDK6	0.008	0.034	-9999	-0.51	2	2
CCND3	0.055	0.043	-9999	-0.43	1	1

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.015	0.062	-10000	0	-0.26	28	28
ER alpha/Gai/GDP/Gbeta gamma	0.003	0.092	-10000	0	-0.37	14	14
AKT1	0.007	0.12	-10000	0	-0.72	12	12
PIK3CA	0.01	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	0.003	0.12	-10000	0	-0.73	12	12
mol:Ca2+	0.013	0.091	-10000	0	-0.41	15	15
IGF1R	0.008	0.033	-10000	0	-0.5	2	2
E2/ER alpha (dimer)/Striatin	-0.017	0.07	-10000	0	-0.3	26	26
SHC1	0.01	0	-10000	0	-10000	0	0
apoptosis	-0.007	0.12	0.69	12	-10000	0	12
RhoA/GTP	-0.011	0.047	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.026	0.076	-10000	0	-0.38	14	14
regulation of stress fiber formation	-0.029	0.051	0.36	1	-10000	0	1
E2/ERA-ERB (dimer)	-0.018	0.071	-10000	0	-0.3	27	27
KRAS	0.01	0	-10000	0	-10000	0	0
G13/GTP	-0.015	0.062	-10000	0	-0.28	25	25
pseudopodium formation	0.029	0.051	-10000	0	-0.36	1	1
E2/ER alpha (dimer)/PELP1	-0.016	0.068	-10000	0	-0.3	25	25
GRB2	0.01	0	-10000	0	-10000	0	0
GNG2	0.008	0.033	-10000	0	-0.5	2	2
GNAO1	0.004	0.053	-10000	0	-0.51	5	5
HRAS	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.011	0.093	-10000	0	-0.43	14	14
E2/ER beta (dimer)	-0.002	0.024	-10000	0	-0.37	2	2
mol:GDP	-0.014	0.062	-10000	0	-0.35	13	13
mol:NADP	0.011	0.093	-10000	0	-0.43	14	14
PIK3R1	0.009	0.024	-10000	0	-0.5	1	1
mol:IP3	0.013	0.095	-10000	0	-0.43	15	15
IGF-1R heterotetramer	0.008	0.033	-10000	0	-0.5	2	2
PLCB1	0.012	0.085	-10000	0	-0.43	14	14
PLCB2	0.007	0.097	-10000	0	-0.45	15	15
IGF1	-0.001	0.074	-10000	0	-0.5	10	10
mol:L-citrulline	0.011	0.093	-10000	0	-0.43	14	14
RHOA	0.01	0	-10000	0	-10000	0	0
Gai/GDP	-0.022	0.076	-10000	0	-0.66	3	3
JNK cascade	-0.002	0.024	-10000	0	-0.36	2	2
BCAR1	0.009	0.024	-10000	0	-0.5	1	1
ESR2	0.008	0.034	-10000	0	-0.51	2	2
GNAQ	0.009	0.024	-10000	0	-0.5	1	1
ESR1	-0.018	0.12	-10000	0	-0.51	25	25
Gq family/GDP/Gbeta gamma	0.023	0.056	-10000	0	-0.43	3	3
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.019	0.048	-10000	0	-0.27	2	2
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.025	0.075	-10000	0	-0.39	13	13
GNAZ	-0.035	0.14	-10000	0	-0.5	41	41
E2/ER alpha (dimer)	-0.02	0.082	-10000	0	-0.37	25	25
STRN	0.009	0.024	-10000	0	-0.5	1	1
GNAL	-0.002	0.078	-10000	0	-0.5	11	11
PELP1	0.01	0	-10000	0	-10000	0	0
MAPK11	0.011	0.032	-10000	0	-0.3	5	5
GNAI2	0.01	0	-10000	0	-10000	0	0
GNAI3	0.01	0	-10000	0	-10000	0	0
GNAI1	0.008	0.033	-10000	0	-0.5	2	2
HBEGF	-0.031	0.11	-10000	0	-0.37	21	21
cAMP biosynthetic process	-0.019	0.069	-10000	0	-0.25	36	36
SRC	0.009	0.088	-10000	0	-0.36	13	13
PI3K	-0.001	0.016	-10000	0	-0.35	1	1
GNB1	0.01	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.013	0.057	-10000	0	-0.32	12	12
SOS1	0.01	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.024	0.071	-10000	0	-0.34	16	16
Gs family/GTP	-0.02	0.07	-10000	0	-0.26	36	36
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0	0	-10000	0	-10000	0	0
vasodilation	0.011	0.089	-10000	0	-0.4	15	15
mol:DAG	0.013	0.095	-10000	0	-0.43	15	15
Gs family/GDP/Gbeta gamma	-0.016	0.064	-10000	0	-0.34	12	12
MSN	0.03	0.054	-10000	0	-0.39	1	1
Gq family/GTP	-0.019	0.082	-10000	0	-0.45	14	14
mol:PI-3-4-5-P3	0.004	0.12	-10000	0	-0.7	12	12
NRAS	0.01	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.011	0.089	0.4	15	-10000	0	15
GRB2/SOS1	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.013	0.058	-10000	0	-0.32	13	13
NOS3	0.01	0.097	-10000	0	-0.45	14	14
GNA11	0.008	0.033	-10000	0	-0.5	2	2
MAPKKK cascade	0.019	0.099	-10000	0	-0.51	13	13
E2/ER alpha (dimer)/PELP1/Src	-0.027	0.079	-10000	0	-0.41	13	13
ruffle organization	0.029	0.051	-10000	0	-0.36	1	1
ROCK2	0.026	0.053	-10000	0	-10000	0	0
GNA14	-0.005	0.087	-10000	0	-0.5	14	14
GNA15	0.01	0	-10000	0	-10000	0	0
GNA13	0.01	0	-10000	0	-10000	0	0
MMP9	-0.034	0.13	-10000	0	-0.37	23	23
MMP2	0.015	0.084	-10000	0	-0.33	13	13

×

S1P4 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
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	0.004	0.053	-9999	-0.51	5	5
CDC42/GTP	-0.028	0.071	-9999	-0.4	4	4
PLCG1	-0.001	0.085	-9999	-0.41	4	4
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.01	0	-9999	-10000	0	0
GNAI3	0.01	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
cell migration	-0.028	0.07	-9999	-0.39	4	4
S1PR5	-0.024	0.13	-9999	-0.5	31	31
S1PR4	-0.019	0.12	-9999	-0.5	26	26
MAPK3	-0.001	0.085	-9999	-0.41	4	4
MAPK1	-0.001	0.085	-9999	-0.41	4	4
S1P/S1P5/Gi	-0.011	0.094	-9999	-0.26	33	33
GNAI1	0.008	0.033	-9999	-0.5	2	2
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.02	0.074	-9999	-0.3	31	31
RHOA	0.01	0.061	-9999	-10000	0	0
S1P/S1P4/Gi	-0.009	0.089	-9999	-0.25	29	29
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.035	0.14	-9999	-0.5	41	41
S1P/S1P4/G12/G13	-0.015	0.061	-9999	-0.26	26	26
GNA12	0.01	0	-9999	-10000	0	0
GNA13	0.01	0	-9999	-10000	0	0
CDC42	0.01	0	-9999	-10000	0	0

×

ErbB2/ErbB3 signaling events

Figure S82. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S82. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.015	0.005	-9999	-10000	0	0
RAS family/GTP	-0.039	0.075	-9999	-10000	0	0
NFATC4	-0.007	0.087	-9999	-0.35	2	2
ERBB2IP	0.01	0.002	-9999	-10000	0	0
HSP90 (dimer)	0.01	0	-9999	-10000	0	0
mammary gland morphogenesis	-0.047	0.091	-9999	-0.42	1	1
JUN	0.019	0.064	-9999	-0.32	1	1
HRAS	0.01	0.001	-9999	-10000	0	0
DOCK7	-0.017	0.1	-9999	-0.4	1	1
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.053	0.1	-9999	-0.51	1	1
AKT1	0.008	0.003	-9999	-10000	0	0
BAD	0.015	0.002	-9999	-10000	0	0
MAPK10	-0.04	0.071	-9999	-0.27	21	21
mol:GTP	0	0.001	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.025	0.11	-9999	-0.45	1	1
RAF1	0.004	0.094	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 2	-0.034	0.09	-9999	-0.27	59	59
STAT3	0.001	0.002	-9999	-10000	0	0
cell migration	-0.003	0.078	-9999	-0.22	20	20
mol:PI-3-4-5-P3	-0.001	0.002	-9999	-10000	0	0
cell proliferation	-0.006	0.17	-9999	-0.58	16	16
FOS	-0.006	0.16	-9999	-0.44	43	43
NRAS	0.01	0.001	-9999	-10000	0	0
mol:Ca2+	-0.047	0.091	-9999	-0.42	1	1
MAPK3	0	0.14	-9999	-0.49	12	12
MAPK1	0	0.14	-9999	-0.49	12	12
JAK2	-0.017	0.1	-9999	-0.4	1	1
NF2	-0.002	0.004	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.031	0.11	-9999	-0.24	96	96
NRG1	-0.094	0.21	-9999	-0.5	95	95
GRB2/SOS1	0	0	-9999	-10000	0	0
MAPK8	-0.018	0.11	-9999	-0.34	1	1
MAPK9	-0.023	0.045	-9999	-0.2	1	1
ERBB2	-0.002	0.03	-9999	-0.38	3	3
ERBB3	0.006	0.033	-9999	-0.5	2	2
SHC1	0.01	0.002	-9999	-10000	0	0
RAC1	0.01	0	-9999	-10000	0	0
apoptosis	0.001	0.007	-9999	-10000	0	0
STAT3 (dimer)	0.001	0.003	-9999	-10000	0	0
RNF41	0.018	0.009	-9999	-10000	0	0
FRAP1	0.007	0.002	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.032	0.062	-9999	-0.28	1	1
ErbB2/ErbB2/HSP90 (dimer)	-0.002	0.025	-9999	-0.31	3	3
CHRNA1	0	0.14	-9999	-0.54	13	13
myelination	-0.004	0.086	-9999	-0.33	2	2
PPP3CB	-0.015	0.095	-9999	-0.37	1	1
KRAS	0.01	0.001	-9999	-10000	0	0
RAC1-CDC42/GDP	-0.04	0.082	-9999	-0.28	1	1
NRG2	-0.05	0.16	-9999	-0.5	54	54
mol:GDP	-0.031	0.11	-9999	-0.24	96	96
SOS1	0.01	0.001	-9999	-10000	0	0
MAP2K2	0.01	0.093	-9999	-0.31	5	5
SRC	0.01	0	-9999	-10000	0	0
mol:cAMP	-0.001	0.001	-9999	-10000	0	0
PTPN11	-0.017	0.1	-9999	-0.4	1	1
MAP2K1	-0.013	0.14	-9999	-0.48	11	11
heart morphogenesis	-0.047	0.091	-9999	-0.42	1	1
RAS family/GDP	-0.039	0.076	-9999	-10000	0	0
GRB2	0.01	0.001	-9999	-10000	0	0
PRKACA	-0.004	0.007	-9999	-10000	0	0
CHRNE	0.012	0.022	-9999	-0.16	4	4
HSP90AA1	0.01	0	-9999	-10000	0	0
activation of caspase activity	-0.008	0.003	-9999	-10000	0	0
nervous system development	-0.047	0.091	-9999	-0.42	1	1
CDC42	0.01	0	-9999	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	0.019	0.1	-9999	-0.33	31	31
MAP3K8	0.007	0.033	-9999	-0.5	2	2
FOS	0.021	0.071	-9999	-0.37	5	5
PRKCA	0.008	0.034	-9999	-0.51	2	2
PTPN7	0.011	0.003	-9999	-10000	0	0
HRAS	0.01	0.001	-9999	-10000	0	0
PRKCB	-0.004	0.084	-9999	-0.5	13	13
NRAS	0.01	0.001	-9999	-10000	0	0
RAS family/GTP	0	0	-9999	-10000	0	0
MAPK3	0.019	0.041	-9999	-0.21	4	4
MAP2K1	0.017	0.081	-9999	-0.41	15	15
ELK1	0.009	0.005	-9999	-10000	0	0
BRAF	-0.014	0.069	-9999	-0.39	15	15
mol:GTP	0	0.001	-9999	-0.005	31	31
MAPK1	0.019	0.041	-9999	-0.21	4	4
RAF1	-0.014	0.069	-9999	-0.39	15	15
KRAS	0.01	0.001	-9999	-10000	0	0

×

Regulation of nuclear SMAD2/3 signaling

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
EP300	0.013	0.007	-10000	0	-10000	0	0
HSPA8	0.008	0.004	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.013	0.08	0.2	1	-0.32	24	25
AKT1	0.007	0.02	-10000	0	-10000	0	0
GSC	-0.025	0.1	-10000	0	-10000	0	0
NKX2-5	-0.028	0.13	-10000	0	-0.51	30	30
muscle cell differentiation	0.02	0.053	0.33	2	-10000	0	2
SMAD2-3/SMAD4/SP1	0.043	0.057	-10000	0	-10000	0	0
SMAD4	0.017	0.024	-10000	0	-10000	0	0
CBFB	0.01	0	-10000	0	-10000	0	0
SAP18	0.01	0.001	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.01	0.074	-10000	0	-0.29	28	28
SMAD3/SMAD4/VDR	0.01	0.032	-10000	0	-0.32	1	1
MYC	0.011	0.039	-10000	0	-0.5	2	2
CDKN2B	-0.061	0.33	-10000	0	-1.3	33	33
AP1	0.026	0.085	-10000	0	-0.49	4	4
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.044	0.022	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.011	0.094	-10000	0	-0.31	32	32
SP3	0.012	0	-10000	0	-10000	0	0
CREB1	0.01	0	-10000	0	-10000	0	0
FOXH1	-0.056	0.17	-10000	0	-0.51	58	58
SMAD3/SMAD4/GR	0.002	0.023	-10000	0	-10000	0	0
GATA3	0.008	0.044	-10000	0	-0.5	3	3
SKI/SIN3/HDAC complex/NCoR1	0.031	0.015	-10000	0	-10000	0	0
MEF2C/TIF2	-0.042	0.1	-10000	0	-0.48	6	6
endothelial cell migration	-0.005	0.069	1.3	1	-10000	0	1
MAX	0.009	0.003	-10000	0	-10000	0	0
RBBP7	0.01	0.001	-10000	0	-10000	0	0
RBBP4	0.01	0.001	-10000	0	-10000	0	0
RUNX2	0.002	0.064	-10000	0	-0.51	7	7
RUNX3	0.008	0.033	-10000	0	-0.5	2	2
RUNX1	0.01	0	-10000	0	-10000	0	0
CTBP1	0.01	0	-10000	0	-10000	0	0
NR3C1	0.009	0.003	-10000	0	-10000	0	0
VDR	0.008	0.034	-10000	0	-0.51	2	2
CDKN1A	0.049	0.069	-10000	0	-1.2	1	1
KAT2B	0.011	0.002	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	-0.042	0.1	-10000	0	-0.31	54	54
DCP1A	0.01	0	-10000	0	-10000	0	0
SKI	0.01	0.001	-10000	0	-10000	0	0
SERPINE1	0.005	0.07	-10000	0	-1.3	1	1
SMAD3/SMAD4/ATF2	0.003	0.022	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	-0.012	0.07	-10000	0	-0.3	23	23
SAP30	0.01	0.001	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.012	0.026	-10000	0	-10000	0	0
JUN	0.026	0.084	-10000	0	-0.49	4	4
SMAD3/SMAD4/IRF7	0.001	0.038	-10000	0	-0.43	2	2
TFE3	0.015	0.003	-10000	0	-10000	0	0
COL1A2	-0.011	0.094	-10000	0	-0.4	20	20
mesenchymal cell differentiation	0.002	0.045	0.32	7	-10000	0	7
DLX1	-0.028	0.13	-10000	0	-0.51	31	31
TCF3	0.01	0	-10000	0	-10000	0	0
FOS	-0.02	0.13	-10000	0	-0.5	31	31
SMAD3/SMAD4/Max	0.002	0.023	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.005	0.012	-10000	0	-10000	0	0
ZBTB17	0.012	0.015	-10000	0	-10000	0	0
LAMC1	0.044	0.027	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.003	0.022	-10000	0	-10000	0	0
IRF7	0.008	0.039	-10000	0	-0.58	2	2
ESR1	-0.018	0.12	-10000	0	-0.5	25	25
HNF4A	-0.11	0.22	-10000	0	-0.51	102	102
MEF2C	-0.016	0.12	-10000	0	-0.51	4	4
SMAD2-3/SMAD4	-0.006	0.027	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.008	0.018	-10000	0	-10000	0	0
IGHV3OR16-13	-0.001	0.006	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.01	0	-10000	0	-10000	0	0
CREBBP	0.012	0.005	-10000	0	-10000	0	0
SKIL	0.01	0	-10000	0	-10000	0	0
HDAC1	0.01	0.001	-10000	0	-10000	0	0
HDAC2	0.01	0.001	-10000	0	-10000	0	0
SNIP1	0.008	0.004	-10000	0	-10000	0	0
GCN5L2	0.002	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.005	0.025	-10000	0	-10000	0	0
MSG1/HSC70	-0.022	0.086	-10000	0	-0.36	29	29
SMAD2	0.007	0.021	-10000	0	-10000	0	0
SMAD3	0.019	0.022	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.036	0.025	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.015	0.012	-10000	0	-10000	0	0
NCOR1	0.01	0.001	-10000	0	-10000	0	0
NCOA2	0.005	0.047	-10000	0	-0.5	4	4
NCOA1	0.01	0	-10000	0	-10000	0	0
MYOD/E2A	-0.002	0.029	-10000	0	-0.36	3	3
SMAD2-3/SMAD4/SP1/MIZ-1	0.049	0.054	-10000	0	-10000	0	0
IFNB1	0.031	0.05	-10000	0	-0.57	2	2
SMAD3/SMAD4/MEF2C	-0.003	0.12	-10000	0	-0.5	4	4
CITED1	-0.023	0.12	-10000	0	-0.5	29	29
SMAD2-3/SMAD4/ARC105	-0.004	0.023	-10000	0	-10000	0	0
RBL1	0.01	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.017	0.13	-10000	0	-0.46	33	33
RUNX1-3/PEBPB2	-0.001	0.019	-10000	0	-0.29	2	2
SMAD7	0.05	0.093	-10000	0	-0.58	3	3
MYC/MIZ-1	0.009	0.045	-10000	0	-0.36	2	2
SMAD3/SMAD4	0.025	0.065	0.29	1	-0.44	1	2
IL10	0.032	0.08	-10000	0	-0.49	9	9
PIASy/HDAC complex	0.008	0.004	-10000	0	-10000	0	0
PIAS3	0.011	0.003	-10000	0	-10000	0	0
CDK2	0.012	0.005	-10000	0	-10000	0	0
IL5	0.033	0.046	-10000	0	-10000	0	0
CDK4	0.008	0.049	-10000	0	-0.51	4	4
PIAS4	0.008	0.004	-10000	0	-10000	0	0
ATF3	-0.015	0.11	-10000	0	-0.5	23	23
SMAD3/SMAD4/SP1	-0.002	0.035	-10000	0	-10000	0	0
FOXG1	-0.055	0.16	-10000	0	-0.51	52	52
FOXO3	0.015	0.026	-10000	0	-10000	0	0
FOXO1	0.015	0.025	-10000	0	-10000	0	0
FOXO4	0.015	0.025	-10000	0	-10000	0	0
heart looping	-0.016	0.12	-10000	0	-0.51	4	4
CEBPB	0.008	0.01	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.019	0.084	-10000	0	-0.32	31	31
MYOD1	-0.002	0.041	-10000	0	-0.51	3	3
SMAD3/SMAD4/HNF4	-0.066	0.13	-10000	0	-0.31	99	99
SMAD3/SMAD4/GATA3	-0.001	0.045	-10000	0	-0.34	1	1
SnoN/SIN3/HDAC complex/NCoR1	0.01	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.004	0.029	-10000	0	-0.32	2	2
SMAD3/SMAD4/SP1-3	0.01	0.037	-10000	0	-10000	0	0
MED15	0.01	0	-10000	0	-10000	0	0
SP1	0.013	0.022	-10000	0	-10000	0	0
SIN3B	0.01	0.001	-10000	0	-10000	0	0
SIN3A	0.01	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.038	0.12	-10000	0	-0.39	17	17
ITGB5	0.05	0.035	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.035	0.009	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.039	0.11	-10000	0	-0.31	62	62
AR	-0.059	0.17	-10000	0	-0.5	63	63
negative regulation of cell growth	0.035	0.045	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	-0.001	0.034	-10000	0	-0.32	3	3
E2F5	0.006	0.042	-10000	0	-0.51	3	3
E2F4	0.01	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.031	0.081	-10000	0	-0.32	5	5
SMAD2-3/SMAD4/FOXO1-3a-4	0.024	0.095	-10000	0	-0.31	33	33
TFDP1	0.009	0.024	-10000	0	-0.51	1	1
SMAD3/SMAD4/AP1	0.03	0.086	-10000	0	-0.5	4	4
SMAD3/SMAD4/RUNX2	-0.002	0.045	-10000	0	-0.32	7	7
TGIF2	0.01	0	-10000	0	-10000	0	0
TGIF1	0.01	0	-10000	0	-10000	0	0
ATF2	0.01	0	-10000	0	-10000	0	0

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.009	0.023	-10000	0	-10000	0	0
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	-0.002	0.079	0.52	2	-10000	0	2
IL27/IL27R/JAK1	-0.028	0.086	-10000	0	-1.1	1	1
TBX21	0	0.14	-10000	0	-0.5	21	21
IL12B	0.004	0.054	-10000	0	-0.51	5	5
IL12A	0.004	0.042	-10000	0	-0.36	6	6
IL6ST	-0.009	0.097	-10000	0	-0.51	17	17
IL27RA/JAK1	0.011	0.057	-10000	0	-1.2	1	1
IL27	-0.005	0.082	-10000	0	-0.51	12	12
TYK2	0.01	0.004	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.064	0.12	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.002	0.079	0.52	2	-10000	0	2
T cell proliferation during immune response	-0.002	0.079	0.52	2	-10000	0	2
MAPKKK cascade	0.002	0.079	-10000	0	-0.52	2	2
STAT3	0.01	0	-10000	0	-10000	0	0
STAT2	0.01	0	-10000	0	-10000	0	0
STAT1	0.01	0.002	-10000	0	-10000	0	0
IL12RB1	-0.007	0.09	-10000	0	-0.5	15	15
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.009	0.16	-10000	0	-0.52	19	19
IL27/IL27R/JAK2/TYK2	0.002	0.079	-10000	0	-0.53	2	2
positive regulation of T cell mediated cytotoxicity	0.002	0.079	-10000	0	-0.52	2	2
STAT1 (dimer)	-0.047	0.13	0.48	1	-0.67	7	8
JAK2	0.009	0.024	-10000	0	-0.5	1	1
JAK1	0.01	0.002	-10000	0	-10000	0	0
STAT2 (dimer)	0.007	0.075	-10000	0	-0.5	2	2
T cell proliferation	-0.05	0.13	-10000	0	-0.45	15	15
IL12/IL12R/TYK2/JAK2	0.008	0.079	-10000	0	-0.6	2	2
IL17A	-0.064	0.12	-10000	0	-10000	0	0
mast cell activation	-0.002	0.079	0.52	2	-10000	0	2
IFNG	0.001	0.027	-10000	0	-0.12	9	9
T cell differentiation	-0.003	0.005	-10000	0	-0.021	19	19
STAT3 (dimer)	0.007	0.075	-10000	0	-0.5	2	2
STAT5A (dimer)	0.006	0.08	-10000	0	-0.62	2	2
STAT4 (dimer)	0.007	0.075	-10000	0	-0.5	2	2
STAT4	0.01	0	-10000	0	-10000	0	0
T cell activation	-0.006	0.007	0.12	1	-10000	0	1
IL27R/JAK2/TYK2	-0.016	0.072	-10000	0	-1.1	1	1
GATA3	0.003	0.084	-10000	0	-1.2	2	2
IL18	0.002	0.051	-10000	0	-0.36	9	9
positive regulation of mast cell cytokine production	0.007	0.074	-10000	0	-0.49	2	2
IL27/EBI3	-0.005	0.063	-10000	0	-0.36	14	14
IL27RA	0.001	0.059	-10000	0	-1.2	1	1
IL6	-0.11	0.21	-10000	0	-0.5	106	106
STAT5A	0.009	0.024	-10000	0	-0.5	1	1
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	0.003	0.022	0.46	1	-10000	0	1
IL1B	-0.012	0.085	-10000	0	-0.36	26	26
EBI3	0.007	0.034	-10000	0	-0.51	2	2
TNF	-0.006	0.073	-10000	0	-0.36	19	19

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.009	0.024	-9999	-0.5	1	1
SPHK1	0.005	0.048	-9999	-0.51	4	4
GNAI2	0.01	0	-9999	-10000	0	0
mol:S1P	0.016	0.02	-9999	-0.27	1	1
GNAO1	0.004	0.053	-9999	-0.51	5	5
mol:Sphinganine-1-P	0.014	0.039	-9999	-0.36	5	5
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	-0.001	0.011	-9999	-10000	0	0
GNAI3	0.01	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
S1PR3	0.009	0.024	-9999	-0.51	1	1
S1PR2	0.01	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.002	0.015	-9999	-0.23	1	1
S1PR5	-0.024	0.13	-9999	-0.5	31	31
S1PR4	-0.019	0.12	-9999	-0.5	26	26
GNAI1	0.008	0.033	-9999	-0.5	2	2
S1P/S1P5/G12	-0.018	0.064	-9999	-0.25	31	31
S1P/S1P3/Gq	0.02	0.057	-9999	-0.26	16	16
S1P/S1P4/Gi	-0.003	0.091	-9999	-0.42	5	5
GNAQ	0.009	0.024	-9999	-0.5	1	1
GNAZ	-0.035	0.14	-9999	-0.5	41	41
GNA14	-0.005	0.087	-9999	-0.5	14	14
GNA15	0.01	0	-9999	-10000	0	0
GNA12	0.01	0	-9999	-10000	0	0
GNA13	0.01	0	-9999	-10000	0	0
GNA11	0.008	0.033	-9999	-0.5	2	2
ABCC1	0.01	0	-9999	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.024	0	-9999	-10000	0	0
SNTA1	0.006	0.042	-9999	-0.51	3	3
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.022	0.026	-9999	-0.3	3	3
MAPK12	0.013	0.057	-9999	-0.26	19	19
CCND1	0.007	0.057	-9999	-0.43	6	6
p38 gamma/SNTA1	0.015	0.057	-9999	-10000	0	0
MAP2K3	0.01	0	-9999	-10000	0	0
PKN1	0.01	0	-9999	-10000	0	0
G2/M transition checkpoint	0.013	0.056	-9999	-0.26	19	19
MAP2K6	0.007	0.062	-9999	-0.3	19	19
MAPT	0.005	0.073	-9999	-0.29	24	24
MAPK13	0.018	0	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.013	0.015	-9999	-0.31	1	1

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	0.003	0.058	-9999	-0.5	6	6
CLTC	0.01	0.048	-9999	-10000	0	0
calcium ion-dependent exocytosis	0.02	0.003	-9999	-10000	0	0
Dynamin 2/GTP	-0.027	0.082	-9999	-0.27	47	47
EXOC4	0.01	0	-9999	-10000	0	0
CD59	0.013	0.031	-9999	-10000	0	0
CPE	0.004	0.059	-9999	-0.31	16	16
CTNNB1	0.01	0	-9999	-10000	0	0
membrane fusion	0	0	-9999	-10000	0	0
CTNND1	-0.002	0.082	-9999	-10000	0	0
DNM2	0.01	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.018	0.022	-9999	-10000	0	0
TSHR	-0.017	0.096	-9999	-0.31	46	46
INS	0.007	0.008	-9999	-10000	0	0
BIN1	0.01	0	-9999	-10000	0	0
mol:Choline	0	0	-9999	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-9999	-10000	0	0
mol:GDP	-0.018	0.097	-9999	-0.31	47	47
membrane depolarization	0	0	-9999	-10000	0	0
ARF6	0.01	0	-9999	-10000	0	0
mol:Ca2+	-0.027	0.082	-9999	-0.27	47	47
JUP	0.012	0.032	-9999	-10000	0	0
ASAP2/amphiphysin II	0	0	-9999	-10000	0	0
ARF6/GTP	0	0	-9999	-10000	0	0
CDH1	0.012	0.034	-9999	-10000	0	0
clathrin-independent pinocytosis	0	0	-9999	-10000	0	0
MAPK8IP3	0.009	0.024	-9999	-0.51	1	1
positive regulation of endocytosis	0	0	-9999	-10000	0	0
EXOC2	0.01	0	-9999	-10000	0	0
substrate adhesion-dependent cell spreading	0.034	0	-9999	-10000	0	0
insulin receptor binding	0	0	-9999	-10000	0	0
SPAG9	0.01	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.019	0.057	-9999	-10000	0	0
positive regulation of phagocytosis	0.015	0	-9999	-10000	0	0
ARF6/GTP/JIP3	-0.001	0.014	-9999	-0.31	1	1
ACAP1	0.02	0.008	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CHRM2	-0.028	0.089	-9999	-0.34	10	10
clathrin heavy chain/ACAP1	0.015	0.045	-9999	-10000	0	0
JIP4/KLC1	0	0	-9999	-10000	0	0
EXOC1	0.01	0	-9999	-10000	0	0
exocyst	0.034	0	-9999	-10000	0	0
RALA/GTP	0	0	-9999	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0	0	-9999	-10000	0	0
receptor recycling	0	0	-9999	-10000	0	0
CTNNA1	-0.002	0.082	-9999	-0.25	47	47
NME1	-0.018	0.097	-9999	-0.31	47	47
clathrin coat assembly	0.01	0.047	-9999	-10000	0	0
IL2RA	0.003	0.047	-9999	-10000	0	0
VAMP3	0.015	0	-9999	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.014	0.044	-9999	-0.34	3	3
EXOC6	0.01	0	-9999	-10000	0	0
PLD1	0	0	-9999	-10000	0	0
PLD2	0	0	-9999	-10000	0	0
EXOC5	0.01	0	-9999	-10000	0	0
PIP5K1C	0.019	0.023	-9999	-10000	0	0
SDC1	0.013	0.031	-9999	-10000	0	0
ARF6/GDP	-0.018	0.097	-9999	-0.31	47	47
EXOC7	0.01	0	-9999	-10000	0	0
E-cadherin/beta catenin	-0.02	0.058	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
endocytosis	0	0	-9999	-10000	0	0
SCAMP2	0.01	0	-9999	-10000	0	0
ADRB2	-0.082	0.14	-9999	-0.36	31	31
EXOC3	0.01	0	-9999	-10000	0	0
ASAP2	0.01	0	-9999	-10000	0	0
Dynamin 2/GDP	-0.01	0.088	-9999	-0.27	47	47
KLC1	0.01	0	-9999	-10000	0	0
AVPR2	-0.04	0.12	-9999	-0.36	15	15
RALA	0.01	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.018	0.052	-9999	-10000	0	0

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.063	0.17	-9999	-0.78	5	5
RAD9A	0.01	0	-9999	-10000	0	0
AP1	-0.018	0.097	-9999	-0.36	35	35
IFNAR2	0.008	0.005	-9999	-10000	0	0
AKT1	0.002	0.045	-9999	-0.22	7	7
ER alpha/Oestrogen	-0.02	0.083	-9999	-0.37	25	25
NFX1/SIN3/HDAC complex	0.027	0.018	-9999	-10000	0	0
EGF	-0.093	0.21	-9999	-0.52	90	90
SMG5	0.01	0	-9999	-10000	0	0
SMG6	0.01	0	-9999	-10000	0	0
SP3/HDAC2	0.012	0.009	-9999	-10000	0	0
TERT/c-Abl	-0.085	0.14	-9999	-0.73	5	5
SAP18	0.007	0.004	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	-0.034	0.14	-9999	-0.51	37	37
WRN	0.01	0	-9999	-10000	0	0
SP1	0.009	0.006	-9999	-10000	0	0
SP3	0.007	0.005	-9999	-10000	0	0
TERF2IP	0.01	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.079	0.12	-9999	-0.65	5	5
Mad/Max	0.009	0.009	-9999	-10000	0	0
TERT	-0.065	0.18	-9999	-0.8	5	5
CCND1	-0.059	0.2	-9999	-1.2	6	6
MAX	0.007	0.005	-9999	-10000	0	0
RBBP7	0.007	0.004	-9999	-10000	0	0
RBBP4	0.007	0.004	-9999	-10000	0	0
TERF2	0	0	-9999	-10000	0	0
PTGES3	0.01	0	-9999	-10000	0	0
SIN3A	0.007	0.004	-9999	-10000	0	0
Telomerase/911	0.022	0.029	-9999	-10000	0	0
CDKN1B	-0.004	0.087	-9999	-0.3	9	9
RAD1	0.01	0	-9999	-10000	0	0
XRCC5	0.01	0	-9999	-10000	0	0
XRCC6	0.01	0	-9999	-10000	0	0
SAP30	0.007	0.004	-9999	-10000	0	0
TRF2/PARP2	0	0	-9999	-10000	0	0
UBE3A	0.007	0.005	-9999	-10000	0	0
JUN	0.003	0.047	-9999	-0.5	4	4
E6	-0.002	0.004	-9999	-10000	0	0
HPV-16 E6/E6AP	0.006	0.005	-9999	-10000	0	0
FOS	-0.026	0.13	-9999	-0.5	31	31
IFN-gamma/IRF1	-0.029	0.097	-9999	-0.35	39	39
PARP2	0.01	0	-9999	-10000	0	0
BLM	-0.043	0.16	-9999	-0.51	47	47
Telomerase	-0.02	0.056	-9999	-10000	0	0
IRF1	0.01	0.007	-9999	-10000	0	0
ESR1	-0.02	0.12	-9999	-0.51	25	25
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.03	0.02	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.03	0.02	-9999	-10000	0	0
HDAC1	0.007	0.004	-9999	-10000	0	0
HDAC2	0.008	0.006	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.02	0.004	-9999	-10000	0	0
ABL1	0.01	0	-9999	-10000	0	0
MXD1	0.007	0.005	-9999	-10000	0	0
MRE11A	0.01	0	-9999	-10000	0	0
HUS1	0.01	0	-9999	-10000	0	0
RPS6KB1	0.01	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.081	0.13	-9999	-0.73	4	4
NR2F2	0.013	0.007	-9999	-10000	0	0
MAPK3	0.011	0.008	-9999	-10000	0	0
MAPK1	0.011	0.008	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.011	0.002	-9999	-10000	0	0
NFKB1	0.01	0	-9999	-10000	0	0
HNRNPC	0.01	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0	0	-9999	-10000	0	0
NBN	0.01	0	-9999	-10000	0	0
EGFR	-0.008	0.089	-9999	-0.51	14	14
mol:Oestrogen	-0.001	0.002	-9999	-10000	0	0
EGF/EGFR	-0.081	0.16	-9999	-0.38	101	101
MYC	0.005	0.034	-9999	-0.51	2	2
IL2	0.003	0.011	-9999	-10000	0	0
KU	0	0	-9999	-10000	0	0
RAD50	0.01	0	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
TGFB1	0.011	0.002	-9999	-10000	0	0
TRF2/BLM	-0.034	0.1	-9999	-0.34	47	47
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.082	0.14	-9999	-0.72	5	5
SP1/HDAC2	0.013	0.011	-9999	-10000	0	0
PINX1	0.01	0	-9999	-10000	0	0
Telomerase/EST1A	-0.079	0.12	-9999	-0.65	5	5
Smad3/Myc	0.021	0.021	-9999	-0.29	2	2
911 complex	0	0	-9999	-10000	0	0
IFNG	-0.033	0.14	-9999	-0.5	39	39
Telomerase/PinX1	-0.079	0.12	-9999	-0.65	5	5
Telomerase/AKT1/mTOR/p70S6K	0.006	0.053	-9999	-10000	0	0
SIN3B	0.007	0.004	-9999	-10000	0	0
YWHAE	0.01	0	-9999	-10000	0	0
Telomerase/EST1B	-0.079	0.12	-9999	-0.65	5	5
response to DNA damage stimulus	0.003	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0	0	-9999	-10000	0	0
TRF2/WRN	0	0	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.079	0.12	-9999	-0.65	5	5
E2F1	0	0.064	-9999	-0.52	7	7
ZNFX1	0.007	0.004	-9999	-10000	0	0
PIF1	-0.061	0.18	-9999	-0.51	63	63
NCL	0.01	0	-9999	-10000	0	0
DKC1	0.01	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

Insulin 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
CBL/APS/CAP	-0.013	0.051	-9999	-10000	0	0
TC10/GTP	-0.012	0.048	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	-0.001	0.012	-9999	-0.27	1	1
HRAS	0.01	0	-9999	-10000	0	0
APS homodimer	0.009	0.024	-9999	-0.5	1	1
GRB14	-0.025	0.13	-9999	-0.51	31	31
FOXO3	-0.004	0.026	-9999	-0.52	1	1
AKT1	0.024	0.061	-9999	-10000	0	0
INSR	0.011	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.01	0	-9999	-10000	0	0
SORBS1	-0.017	0.12	-9999	-0.5	25	25
CRK	0.01	0	-9999	-10000	0	0
PTPN1	0.028	0	-9999	-10000	0	0
CAV1	-0.15	0.13	-9999	-0.25	295	295
CBL/APS/CAP/Crk-II/C3G	-0.013	0.054	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/NCK2	-0.001	0.012	-9999	-0.27	1	1
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.015	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.03	0.01	-9999	-10000	0	0
RPS6KB1	0.029	0.058	-9999	-10000	0	0
PARD6A	0.009	0.024	-9999	-0.5	1	1
CBL	0.01	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0	-9999	-10000	0	0
PIK3R1	0.009	0.024	-9999	-0.5	1	1
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.012	0.044	-9999	-10000	0	0
HRAS/GTP	-0.002	0.018	-9999	-10000	0	0
Insulin Receptor	0.011	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.001	0.011	-9999	-10000	0	0
PRKCI	-0.004	0.013	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.015	0.055	-9999	-10000	0	0
SHC1	0.01	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0	0	-9999	-10000	0	0
PI3K	-0.001	0.015	-9999	-10000	0	0
NCK2	0.01	0	-9999	-10000	0	0
RHOQ	0.01	0	-9999	-10000	0	0
mol:H2O2	0	0	-9999	-10000	0	0
HRAS/GDP	0	0	-9999	-10000	0	0
AKT2	0.024	0.061	-9999	-10000	0	0
PRKCZ	-0.007	0.038	-9999	-0.45	3	3
SH2B2	0.009	0.024	-9999	-0.5	1	1
SHC/SHIP	0.024	0.024	-9999	-10000	0	0
F2RL2	-0.033	0.14	-9999	-0.51	38	38
TRIP10	0.01	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	0	0	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0	0	-9999	-10000	0	0
RAPGEF1	0.01	0	-9999	-10000	0	0
RASA1	0.01	0	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	-0.014	0.059	-9999	-0.26	26	26
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0	0	-9999	-10000	0	0
INPP5D	0.019	0.025	-9999	-0.25	4	4
SOS1	0.01	0	-9999	-10000	0	0
SGK1	-0.003	0.037	-9999	-0.79	1	1
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.01	0	-9999	-10000	0	0
IRS1	0.009	0.024	-9999	-0.5	1	1
p62DOK/RasGAP	0	0	-9999	-10000	0	0
INS	0.002	0	-9999	-10000	0	0
mol:PI-3-4-P2	0.019	0.025	-9999	-0.25	4	4
GRB2	0.01	0	-9999	-10000	0	0
EIF4EBP1	0.022	0.072	-9999	-0.41	2	2
PTPRA	0.011	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0.01	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.026	0.011	-9999	-0.22	1	1
Insulin Receptor/Insulin/IRS1	-0.001	0.013	-9999	-0.28	1	1
Insulin Receptor/Insulin/IRS3	0	0	-9999	-10000	0	0
Par3/Par6	-0.021	0.069	-9999	-0.25	34	34

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.025	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP1	0	0	-9999	-10000	0	0
mol:DAG	0.02	0.056	-9999	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	0	0	-9999	-10000	0	0
CaM/Ca2+	0.025	0.053	-9999	-10000	0	0
HIF1A	0.016	0	-9999	-10000	0	0
GAB1	0.009	0.024	-9999	-0.5	1	1
AKT1	0.038	0.045	-9999	-10000	0	0
PLCG1	0.021	0.056	-9999	-10000	0	0
NOS3	0.037	0.055	-9999	-10000	0	0
CBL	0.01	0	-9999	-10000	0	0
mol:NO	0.037	0.054	-9999	-10000	0	0
FLT1	0.024	0	-9999	-10000	0	0
PGF	-0.01	0.1	-9999	-0.51	18	18
VEGFR1 homodimer/NRP2/VEGFR121	-0.002	0.02	-9999	-10000	0	0
CALM1	0.01	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
eNOS/Hsp90	0.041	0.052	-9999	-10000	0	0
endothelial cell proliferation	0.028	0.061	-9999	-0.38	3	3
mol:Ca2+	0.02	0.056	-9999	-10000	0	0
MAPK3	0.03	0.055	-9999	-0.46	1	1
MAPK1	0.03	0.055	-9999	-0.46	1	1
PIK3R1	0.009	0.024	-9999	-0.5	1	1
PLGF homodimer	-0.01	0.1	-9999	-0.51	18	18
PRKACA	0.01	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.31	0.25	-9999	-0.5	295	295
VEGFA homodimer	0.01	0	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0.025	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.035	0.053	-9999	-0.44	1	1
PI3K	-0.01	0.047	-9999	-10000	0	0
PRKCA	0.025	0.057	-9999	-0.49	1	1
PRKCB	0.019	0.071	-9999	-0.49	2	2
VEGFR1 homodimer/PLGF homodimer	0.013	0.062	-9999	-0.3	18	18
VEGFA	0.01	0	-9999	-10000	0	0
VEGFB	0.01	0	-9999	-10000	0	0
mol:IP3	0.02	0.056	-9999	-10000	0	0
RASA1	0.032	0	-9999	-10000	0	0
NRP2	0.007	0.041	-9999	-0.5	3	3
VEGFR1 homodimer	0.024	0	-9999	-10000	0	0
VEGFB homodimer	0.01	0	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.11	0.12	-9999	-0.4	13	13
PTPN11	0.01	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.01	0.047	-9999	-10000	0	0
mol:L-citrulline	0.037	0.054	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0	0	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	0	0	-9999	-10000	0	0
CD2AP	0.01	0	-9999	-10000	0	0
PI3K/GAB1	-0.009	0.045	-9999	-10000	0	0
PDPK1	0.03	0.051	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/SHP2	0	0	-9999	-10000	0	0
mol:NADP	0.037	0.054	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP2	0.023	0.025	-9999	-0.29	3	3

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0	0	-10000	0	-10000	0	0
TRAF2/ASK1	0	0	-10000	0	-10000	0	0
ATM	0.01	0	-10000	0	-10000	0	0
MAP2K3	0.022	0.026	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.026	0.03	-10000	0	-10000	0	0
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.003	0.058	-10000	0	-0.5	6	6
TXN	0.006	0.013	-10000	0	-0.19	2	2
CALM1	0.01	0	-10000	0	-10000	0	0
GADD45A	0.008	0.034	-10000	0	-0.51	2	2
GADD45B	0.005	0.047	-10000	0	-0.5	4	4
MAP3K1	0.01	0	-10000	0	-10000	0	0
MAP3K6	0.01	0	-10000	0	-10000	0	0
MAP3K7	0.01	0	-10000	0	-10000	0	0
MAP3K4	0.01	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0	0	-10000	0	-10000	0	0
TAK1/TAB family	0.001	0.013	0.17	3	-10000	0	3
RAC1/OSM/MEKK3	-0.001	0.012	-10000	0	-0.26	1	1
TRAF2	0.01	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.002	0.009	-10000	0	-10000	0	0
TRAF6	0.007	0	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.081	0.2	-10000	0	-0.51	81	81
CCM2	0.01	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.053	0.12	-10000	0	-0.31	81	81
MAPK11	0.007	0.041	-10000	0	-0.5	3	3
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.047	0.1	-10000	0	-0.27	81	81
OSM/MEKK3	-0.001	0.016	-10000	0	-0.35	1	1
TAOK1	0.013	0.015	-10000	0	-0.31	1	1
TAOK2	0.014	0	-10000	0	-10000	0	0
TAOK3	0.014	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.01	0	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.01	0	-10000	0	-10000	0	0
MAP3K10	0.007	0.041	-10000	0	-0.5	3	3
MAP3K3	0.009	0.024	-10000	0	-0.5	1	1
TRX/ASK1	0.012	0.011	-10000	0	-10000	0	0
GADD45/MTK1/MTK1	-0.006	0.045	-10000	0	-0.5	2	2

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	-0.001	0.017	-9999	-10000	0	0
HDAC3	0.01	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.001	0.014	-9999	-10000	0	0
GATA1/HDAC4	-0.039	0.11	-9999	-0.35	52	52
GATA1/HDAC5	-0.038	0.11	-9999	-0.35	51	51
GATA2/HDAC5	-0.031	0.1	-9999	-0.35	41	41
HDAC5/BCL6/BCoR	0	0	-9999	-10000	0	0
HDAC9	-0.002	0.078	-9999	-0.51	11	11
Glucocorticoid receptor/Hsp90/HDAC6	-0.001	0.014	-9999	-0.3	1	1
HDAC4/ANKRA2	-0.001	0.017	-9999	-0.36	1	1
HDAC5/YWHAB	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.017	0	-9999	-10000	0	0
GATA2	-0.035	0.14	-9999	-0.5	41	41
HDAC4/RFXANK	-0.001	0.017	-9999	-0.36	1	1
BCOR	0.01	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.009	0.024	-9999	-0.5	1	1
HDAC5	0.01	0	-9999	-10000	0	0
GNB1/GNG2	-0.002	0.023	-9999	-0.35	2	2
Histones	0.027	0.03	-9999	-10000	0	0
ADRBK1	0.01	0	-9999	-10000	0	0
HDAC4	0.009	0.024	-9999	-0.51	1	1
XPO1	0.01	0	-9999	-10000	0	0
HDAC5/ANKRA2	0	0	-9999	-10000	0	0
HDAC4/Ubc9	-0.001	0.017	-9999	-0.36	1	1
HDAC7	0.01	0	-9999	-10000	0	0
HDAC5/14-3-3 E	0	0	-9999	-10000	0	0
TUBA1B	0.01	0	-9999	-10000	0	0
HDAC6	0.009	0.024	-9999	-0.51	1	1
HDAC5/RFXANK	0	0	-9999	-10000	0	0
CAMK4	0	0.07	-9999	-0.5	9	9
Tubulin/HDAC6	-0.01	0.053	-9999	-0.3	15	15
SUMO1	0.01	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.01	0	-9999	-10000	0	0
GATA1	-0.047	0.16	-9999	-0.5	51	51
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.01	0	-9999	-10000	0	0
NR3C1	0.01	0	-9999	-10000	0	0
SUMO1/HDAC4	0.023	0.012	-9999	-0.24	1	1
SRF	0.01	0	-9999	-10000	0	0
HDAC4/YWHAB	-0.001	0.017	-9999	-0.36	1	1
Tubulin	-0.011	0.062	-9999	-0.36	14	14
HDAC4/14-3-3 E	-0.001	0.017	-9999	-0.36	1	1
GNB1	0.01	0	-9999	-10000	0	0
RANGAP1	0.01	0	-9999	-10000	0	0
BCL6/BCoR	0	0	-9999	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	-0.001	0.014	-9999	-0.3	1	1
HDAC4/SRF	-0.006	0.042	-9999	-0.29	10	10
HDAC4/ER alpha	-0.02	0.082	-9999	-0.36	26	26
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.027	0.03	-9999	-10000	0	0
cell motility	-0.01	0.053	-9999	-0.3	15	15
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.01	0	-9999	-10000	0	0
HDAC7/HDAC3	0	0	-9999	-10000	0	0
BCL6	0.01	0	-9999	-10000	0	0
HDAC4/CaMK II delta B	0.009	0.024	-9999	-0.51	1	1
Hsp90/HDAC6	-0.001	0.017	-9999	-0.36	1	1
ESR1	-0.018	0.12	-9999	-0.51	25	25
HDAC6/HDAC11	-0.001	0.017	-9999	-0.36	1	1
Ran/GTP/Exportin 1	0	0.01	-9999	-0.23	1	1
NPC	0	0	-9999	-10000	0	0
MEF2C	0.01	0	-9999	-10000	0	0
RAN	0.009	0.024	-9999	-0.51	1	1
HDAC4/MEF2C	-0.001	0.011	-9999	-10000	0	0
GNG2	0.008	0.033	-9999	-0.5	2	2
NCOR2	0.01	0	-9999	-10000	0	0
TUBB2A	-0.006	0.089	-9999	-0.51	14	14
HDAC11	0.01	0	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
RANBP2	0.01	0	-9999	-10000	0	0
ANKRA2	0.01	0	-9999	-10000	0	0
RFXANK	0.01	0	-9999	-10000	0	0
nuclear import	0	0.009	-9999	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.013	0.074	-9999	-0.65	4	4
MAP4K1	0.004	0.052	-9999	-0.5	5	5
MAP3K8	0.008	0.033	-9999	-0.5	2	2
PRKCB	-0.004	0.084	-9999	-0.5	13	13
DBNL	0.01	0	-9999	-10000	0	0
CRKL	0.01	0	-9999	-10000	0	0
MAP3K1	0.025	0.07	-9999	-0.6	4	4
JUN	0.01	0.11	-9999	-0.62	13	13
MAP3K7	0.025	0.07	-9999	-0.6	4	4
GRAP2	-0.005	0.087	-9999	-0.5	14	14
CRK	0.01	0	-9999	-10000	0	0
MAP2K4	0.031	0.076	-9999	-0.68	4	4
LAT	0.009	0.024	-9999	-0.51	1	1
LCP2	0.007	0.041	-9999	-0.5	3	3
MAPK8	0.007	0.11	-9999	-0.64	13	13
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.02	0.074	-9999	-0.64	4	4
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.012	0.069	-9999	-0.61	4	4

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.009	0.024	-10000	0	-0.5	1	1
ANTXR2	0.009	0.024	-10000	0	-0.5	1	1
negative regulation of myeloid dendritic cell antigen processing and presentation	0	0.004	-10000	0	-0.066	2	2
monocyte activation	-0.005	0.094	-10000	0	-0.44	19	19
MAP2K2	0	0.002	-10000	0	-10000	0	0
MAP2K1	0	0.004	-10000	0	-10000	0	0
MAP2K7	0	0.004	-10000	0	-10000	0	0
MAP2K6	-0.01	0.051	-10000	0	-0.27	18	18
CYAA	0.011	0.017	-10000	0	-0.25	2	2
MAP2K4	0	0.004	-10000	0	-10000	0	0
IL1B	-0.002	0.064	-10000	0	-0.26	27	27
Channel	-0.001	0.018	-10000	0	-0.27	2	2
NLRP1	-0.001	0.017	-10000	0	-0.26	2	2
CALM1	0.01	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	0	0.005	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0	0.004	0.066	2	-10000	0	2
MAPK3	0	0.004	-10000	0	-10000	0	0
MAPK1	0	0.004	-10000	0	-10000	0	0
PGR	-0.046	0.099	-10000	0	-0.26	83	83
PA/Cellular Receptors	-0.001	0.019	-10000	0	-0.3	2	2
apoptosis	0	0.004	-10000	0	-0.066	2	2
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.011	0.017	-10000	0	-0.26	2	2
macrophage activation	0.015	0.004	-10000	0	-10000	0	0
TNF	-0.011	0.1	-10000	0	-0.5	19	19
VCAM1	-0.006	0.095	-10000	0	-0.44	19	19
platelet activation	0	0.005	-10000	0	-10000	0	0
MAPKKK cascade	-0.01	0.015	-10000	0	-10000	0	0
IL18	0.008	0.046	-10000	0	-0.31	9	9
negative regulation of macrophage activation	0	0.004	-10000	0	-0.066	2	2
LEF	0	0.004	-10000	0	-0.066	2	2
CASP1	-0.002	0.017	-10000	0	-0.23	2	2
mol:cAMP	0	0.005	-10000	0	-10000	0	0
necrosis	0	0.004	-10000	0	-0.066	2	2
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.001	0.017	-10000	0	-0.25	2	2
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.01	0.001	-9999	-10000	0	0
HDAC2	0.01	0.001	-9999	-10000	0	0
GNB1/GNG2	-0.004	0.034	-9999	-0.3	6	6
forebrain development	-0.014	0.14	-9999	-0.53	18	18
GNAO1	0.003	0.053	-9999	-0.51	5	5
SMO/beta Arrestin2	0.012	0.036	-9999	-0.36	4	4
SMO	0.005	0.048	-9999	-0.51	4	4
ARRB2	0.009	0.004	-9999	-10000	0	0
GLI3/SPOP	0.034	0.037	-9999	-10000	0	0
mol:GTP	0	0.003	-9999	-10000	0	0
GSK3B	0.01	0	-9999	-10000	0	0
GNAI2	0.009	0.004	-9999	-10000	0	0
SIN3/HDAC complex	0.006	0.013	-9999	-10000	0	0
GNAI1	0.007	0.034	-9999	-0.5	2	2
XPO1	0.011	0.005	-9999	-10000	0	0
GLI1/Su(fu)	-0.045	0.11	-9999	-0.55	11	11
SAP30	0.01	0.001	-9999	-10000	0	0
mol:GDP	0.005	0.048	-9999	-0.51	4	4
MIM/GLI2A	0.003	0.04	-9999	-0.53	1	1
IFT88	0.01	0	-9999	-10000	0	0
GNAI3	0.009	0.004	-9999	-10000	0	0
GLI2	0.036	0.012	-9999	-10000	0	0
GLI3	0.03	0.038	-9999	-10000	0	0
CSNK1D	0.01	0	-9999	-10000	0	0
CSNK1E	0.01	0	-9999	-10000	0	0
SAP18	0.01	0.001	-9999	-10000	0	0
embryonic digit morphogenesis	0.01	0	-9999	-10000	0	0
GNG2	0.008	0.033	-9999	-0.5	2	2
Gi family/GTP	0	0.081	-9999	-0.27	21	21
SIN3B	0.01	0.001	-9999	-10000	0	0
SIN3A	0.01	0.001	-9999	-10000	0	0
GLI3/Su(fu)	0.037	0.034	-9999	-10000	0	0
GLI2/Su(fu)	0.04	0.027	-9999	-10000	0	0
FOXA2	-0.17	0.39	-9999	-1	77	77
neural tube patterning	-0.014	0.14	-9999	-0.53	18	18
SPOP	0.01	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.021	0.017	-9999	-10000	0	0
GNB1	0.01	0	-9999	-10000	0	0
CSNK1G2	0.01	0	-9999	-10000	0	0
CSNK1G3	0.01	0	-9999	-10000	0	0
MTSS1	0.003	0.04	-9999	-0.53	1	1
embryonic limb morphogenesis	-0.014	0.14	-9999	-0.53	18	18
SUFU	0.019	0.018	-9999	-10000	0	0
LGALS3	0.01	0	-9999	-10000	0	0
catabolic process	0.054	0.035	-9999	-10000	0	0
GLI3A/CBP	0.005	0.056	-9999	-0.33	12	12
KIF3A	0.01	0	-9999	-10000	0	0
GLI1	-0.014	0.14	-9999	-0.55	18	18
RAB23	0.01	0	-9999	-10000	0	0
CSNK1A1	0.01	0	-9999	-10000	0	0
IFT172	0.01	0	-9999	-10000	0	0
RBBP7	0.01	0.001	-9999	-10000	0	0
Su(fu)/Galectin3	0.021	0.017	-9999	-10000	0	0
GNAZ	-0.036	0.14	-9999	-0.5	41	41
RBBP4	0.01	0.001	-9999	-10000	0	0
CSNK1G1	0.01	0	-9999	-10000	0	0
PIAS1	0.01	0	-9999	-10000	0	0
PRKACA	0.01	0	-9999	-10000	0	0
GLI2/SPOP	0.038	0.012	-9999	-10000	0	0
STK36	0.01	0.005	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.007	0.075	-9999	-0.5	2	2
PTCH1	-0.013	0.17	-9999	-0.86	12	12
MIM/GLI1	-0.044	0.22	-9999	-0.49	82	82
CREBBP	0.005	0.056	-9999	-0.33	12	12
Su(fu)/SIN3/HDAC complex	0.04	0.007	-9999	-10000	0	0

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.009	0.056	-10000	0	-0.35	11	11
MAP4K4	0.029	0.043	-10000	0	-10000	0	0
BAG4	0.009	0.024	-10000	0	-0.51	1	1
PKC zeta/ceramide	-0.011	0.034	0.13	5	-0.25	2	7
NFKBIA	0.01	0	-10000	0	-10000	0	0
BIRC3	0.003	0.058	-10000	0	-0.51	6	6
BAX	-0.002	0.016	-10000	0	-10000	0	0
RIPK1	0.01	0	-10000	0	-10000	0	0
AKT1	0.017	0.007	-10000	0	-10000	0	0
BAD	-0.009	0.032	0.14	6	-10000	0	6
SMPD1	0.016	0.037	-10000	0	-0.16	18	18
RB1	-0.009	0.032	0.14	6	-10000	0	6
FADD/Caspase 8	0.036	0.046	-10000	0	-0.45	1	1
MAP2K4	-0.003	0.03	-10000	0	-10000	0	0
NSMAF	0.01	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.003	0.03	-10000	0	-10000	0	0
EGF	-0.091	0.21	-10000	0	-0.51	90	90
mol:ceramide	-0.017	0.034	0.14	6	-10000	0	6
MADD	0.01	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.009	0.056	-10000	0	-0.35	11	11
ASAH1	0.009	0.024	-10000	0	-0.5	1	1
negative regulation of cell cycle	-0.009	0.032	0.14	6	-10000	0	6
cell proliferation	-0.01	0.029	-10000	0	-10000	0	0
BID	0.02	0.033	-10000	0	-10000	0	0
MAP3K1	-0.009	0.032	0.14	6	-10000	0	6
EIF2A	0.003	0.029	-10000	0	-10000	0	0
TRADD	0.01	0	-10000	0	-10000	0	0
CRADD	0.009	0.024	-10000	0	-0.51	1	1
MAPK3	0.006	0.028	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.006	0.028	-10000	0	-10000	0	0
Cathepsin D/ceramide	-0.01	0.031	-10000	0	-10000	0	0
FADD	0.029	0.043	-10000	0	-10000	0	0
KSR1	-0.009	0.032	0.14	6	-10000	0	6
MAPK8	-0.001	0.032	-10000	0	-0.2	2	2
PRKRA	-0.009	0.032	0.14	6	-10000	0	6
PDGFA	-0.001	0.074	-10000	0	-0.5	10	10
TRAF2	0.01	0	-10000	0	-10000	0	0
IGF1	-0.001	0.074	-10000	0	-0.5	10	10
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.017	0.034	0.14	6	-10000	0	6
CTSD	0.01	0	-10000	0	-10000	0	0
regulation of nitric oxide biosynthetic process	0	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	0.008	0.038	-10000	0	-10000	0	0
PRKCD	0.01	0	-10000	0	-10000	0	0
PRKCZ	0.007	0.041	-10000	0	-0.5	3	3
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.009	0.056	-10000	0	-0.35	11	11
RelA/NF kappa B1	0	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.01	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.024	0.046	-10000	0	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.013	0.059	-10000	0	-0.29	20	20
mol:Sphingosine-1-phosphate	0.009	0.056	-10000	0	-0.35	11	11
MAP2K1	0.003	0.029	-10000	0	-10000	0	0
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.01	0	-10000	0	-10000	0	0
CYCS	-0.004	0.024	0.15	1	-10000	0	1
TNFRSF1A	0.01	0	-10000	0	-10000	0	0
NFKB1	0.01	0	-10000	0	-10000	0	0
TNFR1A/BAG4	-0.001	0.017	-10000	0	-0.36	1	1
EIF2AK2	-0.003	0.03	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.012	0.058	-10000	0	-0.29	19	19
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.028	0.039	-10000	0	-0.58	1	1
MAP2K2	0.003	0.029	-10000	0	-10000	0	0
SMPD3	0.016	0.043	-10000	0	-0.29	1	1
TNF	-0.011	0.1	-10000	0	-0.5	19	19
PKC zeta/PAR4	-0.002	0.028	-10000	0	-0.35	3	3
mol:PHOSPHOCHOLINE	0.023	0.067	0.15	90	-10000	0	90
NF kappa B1/RelA/I kappa B alpha	-0.002	0.019	-10000	0	-10000	0	0
AIFM1	-0.004	0.024	0.15	1	-10000	0	1
BCL2	0.007	0.041	-10000	0	-0.51	3	3

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.01	0	-10000	0	-10000	0	0
NFATC1	0.036	0.04	-10000	0	-0.4	1	1
NFATC2	0.012	0.045	-10000	0	-0.26	2	2
NFATC3	0.013	0.032	-10000	0	-0.37	3	3
YWHAE	0.01	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.016	0.097	-10000	0	-0.37	17	17
Exportin 1/Ran/NUP214	-0.001	0.014	-10000	0	-0.3	1	1
mol:DAG	-0.001	0.003	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.035	0.083	-10000	0	-0.39	15	15
BCL2/BAX	-0.002	0.029	-10000	0	-0.36	3	3
CaM/Ca2+/Calcineurin A alpha-beta B1	0.005	0.007	-10000	0	-10000	0	0
CaM/Ca2+	0.005	0.007	-10000	0	-10000	0	0
BAX	0.01	0	-10000	0	-10000	0	0
MAPK14	0.008	0.004	-10000	0	-10000	0	0
BAD	0.01	0	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.015	0.091	-10000	0	-0.35	17	17
Calcineurin A alpha-beta B1/BCL2	0.007	0.041	-10000	0	-0.51	3	3
FKBP8	0.009	0.024	-10000	0	-0.5	1	1
activation-induced cell death of T cells	0.015	0.09	0.34	17	-10000	0	17
KPNB1	0.01	0	-10000	0	-10000	0	0
KPNA2	0.002	0.064	-10000	0	-0.51	7	7
XPO1	0.01	0.001	-10000	0	-10000	0	0
SFN	0	0.072	-10000	0	-0.51	9	9
MAP3K8	0.006	0.034	-10000	0	-0.5	2	2
NFAT4/CK1 alpha	-0.001	0.017	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.053	0.1	-10000	0	-0.39	5	5
CABIN1	-0.016	0.098	-10000	0	-0.37	17	17
CALM1	0.008	0.004	-10000	0	-10000	0	0
RAN	0.008	0.024	-10000	0	-0.51	1	1
MAP3K1	0.01	0	-10000	0	-10000	0	0
CAMK4	0	0.07	-10000	0	-0.5	9	9
mol:Ca2+	-0.003	0.007	-10000	0	-10000	0	0
MAPK3	0.01	0	-10000	0	-10000	0	0
YWHAH	0.01	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.002	0.023	-10000	0	-0.36	2	2
YWHAB	0.01	0	-10000	0	-10000	0	0
MAPK8	0.008	0.004	-10000	0	-10000	0	0
MAPK9	0.01	0	-10000	0	-10000	0	0
YWHAG	0.01	0	-10000	0	-10000	0	0
FKBP1A	0.01	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	-0.004	0.036	-10000	0	-0.34	3	3
PRKCH	0.01	0	-10000	0	-10000	0	0
CABIN1/Cbp/p300	-0.002	0.004	-10000	0	-10000	0	0
CASP3	0.008	0.004	-10000	0	-10000	0	0
PIM1	0.01	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0	-10000	0	-10000	0	0
apoptosis	0	0.014	0.21	1	-10000	0	1
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.031	0.016	-10000	0	-10000	0	0
PRKCB	-0.004	0.084	-10000	0	-0.5	13	13
PRKCE	0.004	0.052	-10000	0	-0.5	5	5
JNK2/NFAT4	0.016	0.029	-10000	0	-0.33	3	3
BAD/BCL-XL	0	0	-10000	0	-10000	0	0
PRKCD	0.01	0	-10000	0	-10000	0	0
NUP214	0.01	0.001	-10000	0	-10000	0	0
PRKCZ	0.005	0.041	-10000	0	-0.5	3	3
PRKCA	0.008	0.033	-10000	0	-0.5	2	2
PRKCG	-0.038	0.15	-10000	0	-0.51	41	41
PRKCQ	-0.068	0.18	-10000	0	-0.5	71	71
FKBP38/BCL2	-0.003	0.033	-10000	0	-0.36	4	4
EP300	0.008	0.005	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.01	0	-10000	0	-10000	0	0
NFATc/JNK1	0.034	0.042	-10000	0	-0.38	1	1
CaM/Ca2+/FKBP38	-0.001	0.014	-10000	0	-0.31	1	1
FKBP12/FK506	0	0	-10000	0	-10000	0	0
CSNK1A1	0.012	0.009	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.006	0.041	-10000	0	-0.3	9	9
NFATc/ERK1	0.04	0.038	-10000	0	-0.38	1	1
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.035	0.082	-10000	0	-0.39	15	15
NR4A1	-0.056	0.21	-10000	0	-0.48	95	95
GSK3B	0.008	0.004	-10000	0	-10000	0	0
positive T cell selection	0.013	0.031	-10000	0	-0.37	3	3
NFAT1/CK1 alpha	-0.011	0.025	-10000	0	-0.26	1	1
RCH1/ KPNB1	-0.005	0.044	-10000	0	-0.36	7	7
YWHAQ	0.01	0	-10000	0	-10000	0	0
PRKACA	0.008	0.004	-10000	0	-10000	0	0
AKAP5	0.008	0.033	-10000	0	-0.5	2	2
MEF2D	0.008	0.005	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.01	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.034	0.042	-10000	0	-0.38	1	1
CREBBP	0.008	0.005	-10000	0	-10000	0	0
BCL2	0.007	0.041	-10000	0	-0.51	3	3

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.01	0	-10000	0	-10000	0	0
HDAC3	0.01	0	-10000	0	-10000	0	0
VDR	0.008	0.034	-10000	0	-0.51	2	2
Cbp/p300/PCAF	0	0	-10000	0	-10000	0	0
EP300	0.01	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.032	0.019	-10000	0	-10000	0	0
KAT2B	0.01	0	-10000	0	-10000	0	0
MAPK14	0.01	0	-10000	0	-10000	0	0
AKT1	0.016	0.027	0.2	1	-0.23	2	3
RAR alpha/9cRA/Cyclin H	-0.006	0.024	-10000	0	-10000	0	0
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.03	0.02	-10000	0	-10000	0	0
CDC2	0	0	-10000	0	-10000	0	0
response to UV	0.001	0	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.007	0.028	-10000	0	-10000	0	0
NCOR2	0.01	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	-0.002	0.024	-10000	0	-0.37	2	2
RXRs/RARs/NRIP1/9cRA	-0.011	0.068	-10000	0	-0.55	2	2
NCOA2	0.005	0.047	-10000	0	-0.5	4	4
NCOA3	0.01	0	-10000	0	-10000	0	0
NCOA1	0.01	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.008	0.034	-10000	0	-0.51	2	2
RARG	0.011	0	-10000	0	-10000	0	0
RAR gamma1/9cRA	0	0	-10000	0	-10000	0	0
MAPK3	0.01	0	-10000	0	-10000	0	0
MAPK1	0.01	0	-10000	0	-10000	0	0
MAPK8	0.011	0	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.043	0.058	-10000	0	-0.59	2	2
RARA	0.011	0.04	-10000	0	-0.23	2	2
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.028	0.028	-10000	0	-10000	0	0
PRKCA	0.01	0.033	-10000	0	-0.5	2	2
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.025	0.076	-10000	0	-0.59	2	2
RXRG	-0.17	0.18	-10000	0	-0.33	242	242
RXRA	0.018	0.037	-10000	0	-10000	0	0
RXRB	0.003	0.06	-10000	0	-0.31	2	2
VDR/Vit D3/DNA	-0.002	0.024	-10000	0	-0.37	2	2
RBP1	0.003	0.059	-10000	0	-0.51	6	6
CRBP1/9-cic-RA	-0.005	0.042	-10000	0	-0.37	6	6
RARB	0.009	0.033	-10000	0	-0.5	2	2
PRKCG	-0.035	0.15	-10000	0	-0.51	41	41
MNAT1	0.01	0	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.012	0.067	-10000	0	-0.59	2	2
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.003	0.059	-10000	0	-0.45	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.031	0.029	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.025	0.076	-10000	0	-0.59	2	2
positive regulation of DNA binding	-0.006	0.023	-10000	0	-10000	0	0
NRIP1	-0.023	0.072	-10000	0	-0.54	2	2
RXRs/RARs	-0.032	0.077	-10000	0	-0.59	2	2
RXRs/RXRs/DNA/9cRA	-0.047	0.059	-10000	0	-0.61	2	2
PRKACA	0.01	0	-10000	0	-10000	0	0
CDK7	0.01	0	-10000	0	-10000	0	0
TFIIH	0	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.005	0.015	-10000	0	-10000	0	0
CCNH	0.01	0	-10000	0	-10000	0	0
CREBBP	0.01	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	0	0	-10000	0	-10000	0	0

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	0.023	0.016	-9999	-0.22	2	2
epithelial cell differentiation	-0.001	0.016	-9999	-10000	0	0
CYFIP2	0.003	0.057	-9999	-0.5	6	6
ENAH	0.048	0.031	-9999	-0.29	1	1
EGFR	-0.006	0.088	-9999	-0.51	14	14
EPHA2	0	0.07	-9999	-0.5	9	9
MYO6	0.029	0.017	-9999	-10000	0	0
CTNNB1	0.01	0	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.004	0.033	-9999	-0.29	6	6
AQP5	-0.1	0.17	-9999	-0.42	105	105
CTNND1	0.01	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.029	0.016	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.11	0.13	-9999	-0.46	1	1
EGF	-0.091	0.21	-9999	-0.51	90	90
NCKAP1	0.01	0	-9999	-10000	0	0
AQP3	-0.017	0.086	-9999	-0.44	18	18
cortical microtubule organization	-0.001	0.016	-9999	-10000	0	0
GO:0000145	0.028	0.016	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.001	0.016	-9999	-10000	0	0
MLLT4	0.01	0	-9999	-10000	0	0
ARF6/GDP	-0.005	0.032	-9999	-0.39	1	1
ARF6	0.01	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.006	0.037	-9999	-0.26	10	10
mol:Ca2+	0	0	-9999	-10000	0	0
VASP	0.037	0.021	-9999	-10000	0	0
PVRL2	0.01	0	-9999	-10000	0	0
ZYX	0.029	0.02	-9999	-10000	0	0
ARF6/GTP	-0.005	0.034	-9999	-10000	0	0
CDH1	0.008	0.033	-9999	-0.5	2	2
EGFR/EGFR/EGF/EGF	-0.05	0.096	-9999	-0.46	3	3
RhoA/GDP	-0.001	0.014	-9999	-10000	0	0
actin cytoskeleton organization	0.034	0.016	-9999	-10000	0	0
IGF-1R heterotetramer	0.008	0.033	-9999	-0.5	2	2
GIT1	0.01	0	-9999	-10000	0	0
IGF1R	0.008	0.033	-9999	-0.5	2	2
IGF1	-0.001	0.074	-9999	-0.5	10	10
DIAPH1	-0.007	0.061	-9999	-0.55	6	6
Wnt receptor signaling pathway	0.001	0.016	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
RhoA/GTP	-0.005	0.031	-9999	-0.4	1	1
CTNNA1	0.01	0	-9999	-10000	0	0
VCL	0.034	0.017	-9999	-10000	0	0
EFNA1	0.009	0.024	-9999	-0.5	1	1
LPP	0.034	0.02	-9999	-10000	0	0
Ephrin A1/EPHA2	-0.006	0.037	-9999	-0.45	1	1
SEC6/SEC8	-0.001	0.012	-9999	-10000	0	0
MGAT3	-0.11	0.13	-9999	-0.47	1	1
HGF/MET	-0.027	0.077	-9999	-0.46	4	4
HGF	-0.019	0.12	-9999	-0.5	26	26
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.023	0.016	-9999	-0.23	2	2
actin cable formation	0.06	0.029	-9999	-10000	0	0
KIAA1543	0.033	0.028	-9999	-0.45	1	1
KIFC3	0.029	0.02	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
EXOC3	0.01	0	-9999	-10000	0	0
ACTN1	0.029	0.017	-9999	-10000	0	0
NCK1/GIT1	0	0	-9999	-10000	0	0
mol:GDP	-0.001	0.016	-9999	-10000	0	0
EXOC4	0.01	0	-9999	-10000	0	0
STX4	0.029	0.017	-9999	-10000	0	0
PIP5K1C	0.029	0.017	-9999	-10000	0	0
LIMA1	0.01	0	-9999	-10000	0	0
ABI1	0.01	0	-9999	-10000	0	0
ROCK1	-0.004	0.028	-9999	-0.34	1	1
adherens junction assembly	0.045	0.039	-9999	-0.53	2	2
IGF-1R heterotetramer/IGF1	-0.006	0.036	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
MET	-0.022	0.12	-9999	-0.51	29	29
PLEKHA7	0.029	0.017	-9999	-10000	0	0
mol:GTP	-0.005	0.037	-9999	-0.26	10	10
establishment of epithelial cell apical/basal polarity	0.049	0.015	-9999	-10000	0	0
cortical actin cytoskeleton stabilization	0.023	0.016	-9999	-0.22	2	2
regulation of cell-cell adhesion	0.034	0.016	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.023	0.016	-9999	-0.23	2	2

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.004	0.067	-9999	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
CRKL	0.01	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	-0.013	0.044	-9999	-10000	0	0
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.004	0.016	-9999	-0.29	1	1
antigen processing and presentation of peptide antigen via MHC class I	-0.013	0.041	-9999	-0.3	3	3
CaM/Ca2+	-0.016	0.054	-9999	-10000	0	0
RAP1A	0.01	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	0.017	0.064	-9999	-10000	0	0
AKT1	0.026	0.06	-9999	-10000	0	0
MAP2K1	0.025	0.062	-9999	-10000	0	0
MAP3K11	0.016	0.065	-9999	-10000	0	0
IFNGR1	0.009	0.007	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.055	0.11	-9999	-0.38	45	45
Rap1/GTP	-0.012	0.039	-9999	-10000	0	0
CRKL/C3G	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.02	0.064	-9999	-10000	0	0
CEBPB	0.045	0.08	-9999	-0.4	8	8
STAT3	0.01	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.017	0.056	-9999	-10000	0	0
STAT1	0.017	0.064	-9999	-10000	0	0
CALM1	0.01	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.032	0.14	-9999	-0.5	39	39
PIK3CA	0.01	0	-9999	-10000	0	0
STAT1 (dimer)/PIAS1	0.022	0.061	-9999	-10000	0	0
CEBPB/PTGES2/Cbp/p300	-0.01	0.037	-9999	-0.34	1	1
mol:Ca2+	-0.018	0.058	-9999	-10000	0	0
MAPK3	0.034	0.06	-9999	-10000	0	0
STAT1 (dimer)	-0.016	0.056	-9999	-0.42	3	3
MAPK1	0.034	0.06	-9999	-10000	0	0
JAK2	0.008	0.024	-9999	-0.5	1	1
PIK3R1	0.009	0.024	-9999	-0.5	1	1
JAK1	0.009	0.007	-9999	-10000	0	0
CAMK2D	0.01	0	-9999	-10000	0	0
DAPK1	0.041	0.093	-9999	-0.59	8	8
SMAD7	0.028	0.04	-9999	-0.26	1	1
CBL/CRKL/C3G	-0.014	0.047	-9999	-10000	0	0
PI3K	-0.016	0.051	-9999	-10000	0	0
IFNG	-0.032	0.14	-9999	-0.51	39	39
apoptosis	0.029	0.07	-9999	-0.43	8	8
CAMK2G	0.01	0	-9999	-10000	0	0
STAT3 (dimer)	0.01	0	-9999	-10000	0	0
CAMK2A	-0.04	0.15	-9999	-0.5	46	46
CAMK2B	-0.081	0.2	-9999	-0.51	81	81
FRAP1	0.026	0.057	-9999	-10000	0	0
PRKCD	0.027	0.061	-9999	-10000	0	0
RAP1B	0.01	0	-9999	-10000	0	0
negative regulation of cell growth	-0.013	0.041	-9999	-0.3	3	3
PTPN2	0.01	0	-9999	-10000	0	0
EP300	0.01	0	-9999	-10000	0	0
IRF1	0.047	0.051	-9999	-10000	0	0
STAT1 (dimer)/PIASy	-0.015	0.05	-9999	-10000	0	0
SOCS1	0.002	0.007	-9999	-10000	0	0
mol:GDP	-0.014	0.046	-9999	-10000	0	0
CASP1	0.027	0.046	-9999	-0.29	4	4
PTGES2	0.01	0	-9999	-10000	0	0
IRF9	0.041	0.029	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.016	0.05	-9999	-10000	0	0
RAP1/GDP	-0.012	0.039	-9999	-10000	0	0
CBL	0.016	0.064	-9999	-10000	0	0
MAP3K1	0.017	0.065	-9999	-10000	0	0
PIAS1	0.01	0	-9999	-10000	0	0
PIAS4	0.01	0	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.013	0.041	-9999	-0.3	3	3
PTPN11	0.01	0.067	-9999	-10000	0	0
CREBBP	0.01	0	-9999	-10000	0	0
RAPGEF1	0.01	0	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class I

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.011	0.056	-9999	-0.29	18	18
Ran/GTP/Exportin 1/HDAC1	0	0.01	-9999	-0.22	1	1
NF kappa B1 p50/RelA/I kappa B alpha	-0.011	0.053	-9999	-0.27	18	18
SUMO1	0.01	0	-9999	-10000	0	0
ZFPM1	0.009	0.024	-9999	-0.51	1	1
NPC/RanGAP1/SUMO1/Ubc9	0.017	0	-9999	-10000	0	0
FKBP3	0.009	0.024	-9999	-0.51	1	1
Histones	-0.005	0.025	-9999	-10000	0	0
YY1/LSF	0.024	0	-9999	-10000	0	0
SMG5	0.01	0	-9999	-10000	0	0
RAN	0.009	0.024	-9999	-0.51	1	1
I kappa B alpha/HDAC3	-0.009	0.045	-9999	-10000	0	0
I kappa B alpha/HDAC1	0.018	0.036	-9999	-10000	0	0
SAP18	0.01	0	-9999	-10000	0	0
RELA	0.021	0.048	-9999	-10000	0	0
HDAC1/Smad7	-0.001	0.013	-9999	-0.29	1	1
RANGAP1	0.01	0	-9999	-10000	0	0
HDAC3/TR2	0.018	0.036	-9999	-10000	0	0
NuRD/MBD3 Complex	0.037	0.012	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.023	0.044	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.035	0.14	-9999	-0.5	41	41
GATA1	-0.047	0.16	-9999	-0.5	51	51
Mad/Max	0	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.023	0.063	-9999	-0.28	1	1
RBBP7	0.01	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
RBBP4	0.01	0	-9999	-10000	0	0
MAX	0.01	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.01	0	-9999	-10000	0	0
NFKBIA	0.014	0.04	-9999	-10000	0	0
KAT2B	0.01	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.034	0	-9999	-10000	0	0
SIN3 complex	0	0	-9999	-10000	0	0
SMURF1	0.01	0	-9999	-10000	0	0
CHD3	0.01	0	-9999	-10000	0	0
SAP30	0.01	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.01	0	-9999	-10000	0	0
YY1/HDAC3	-0.005	0.026	-9999	-10000	0	0
YY1/HDAC2	0.024	0	-9999	-10000	0	0
YY1/HDAC1	0.024	0	-9999	-10000	0	0
NuRD/MBD2 Complex (MeCP1)	0.038	0	-9999	-10000	0	0
PPARG	-0.046	0.12	-9999	-0.31	70	70
HDAC8/hEST1B	0	0	-9999	-10000	0	0
UBE2I	0.01	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.01	0	-9999	-10000	0	0
TNFRSF1A	0.01	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.018	0.036	-9999	-10000	0	0
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.001	0.013	-9999	-0.29	1	1
CREBBP	0.01	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.039	0.013	-9999	-10000	0	0
HDAC1	0.01	0	-9999	-10000	0	0
HDAC3	0.014	0.04	-9999	-10000	0	0
HDAC2	0.01	0	-9999	-10000	0	0
YY1	0.024	0	-9999	-10000	0	0
HDAC8	0.01	0	-9999	-10000	0	0
SMAD7	0.009	0.024	-9999	-0.5	1	1
NCOR2	0.01	0	-9999	-10000	0	0
MXD1	0.01	0	-9999	-10000	0	0
STAT3	0.02	0	-9999	-10000	0	0
NFKB1	0.01	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.01	0	-9999	-10000	0	0
YY1/LSF/HDAC1	0	0	-9999	-10000	0	0
YY1/SAP30/HDAC1	0	0	-9999	-10000	0	0
EP300	0.01	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.02	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.014	0.04	-9999	-10000	0	0
histone deacetylation	0.038	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	-0.006	0.027	-9999	-10000	0	0
nuclear export	0	0	-9999	-10000	0	0
PRKACA	0.01	0	-9999	-10000	0	0
GATAD2B	0.01	0	-9999	-10000	0	0
GATAD2A	0.01	0	-9999	-10000	0	0
GATA2/HDAC3	-0.006	0.09	-9999	-0.43	4	4
GATA1/HDAC1	-0.038	0.11	-9999	-0.35	51	51
GATA1/HDAC3	-0.016	0.093	-9999	-0.26	51	51
CHD4	0.01	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.014	0.07	-9999	-0.35	19	19
SIN3/HDAC complex/Mad/Max	0.038	0	-9999	-10000	0	0
NuRD Complex	0.043	0.013	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.005	0.025	-9999	-10000	0	0
SIN3B	0.01	0	-9999	-10000	0	0
MTA2	0.01	0	-9999	-10000	0	0
SIN3A	0.01	0	-9999	-10000	0	0
XPO1	0.01	0	-9999	-10000	0	0
SUMO1/HDAC1	0.023	0	-9999	-10000	0	0
HDAC complex	0	0	-9999	-10000	0	0
GATA1/Fog1	-0.039	0.11	-9999	-0.36	51	51
FKBP25/HDAC1/HDAC2	-0.001	0.014	-9999	-0.3	1	1
TNF	-0.011	0.1	-9999	-0.5	19	19
negative regulation of cell growth	0.038	0	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.038	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0.01	-9999	-0.23	1	1
NF kappa B/RelA/I kappa B alpha	-0.011	0.056	-9999	-0.29	18	18
SIN3/HDAC complex/NCoR1	0.036	0	-9999	-10000	0	0
TFCP2	0.01	0	-9999	-10000	0	0
NR2C1	0.01	0	-9999	-10000	0	0
MBD3	0.008	0.033	-9999	-0.5	2	2
MBD2	0.01	0	-9999	-10000	0	0

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.017	0.046	-9999	-10000	0	0
PLK1	-0.13	0.25	-9999	-0.6	42	42
CDKN1B	0.013	0.11	-9999	-10000	0	0
FOXO3	-0.075	0.21	-9999	-0.51	42	42
KAT2B	0.003	0.019	-9999	-10000	0	0
FOXO1/SIRT1	0.014	0.028	-9999	-10000	0	0
CAT	-0.073	0.24	-9999	-1.3	7	7
CTNNB1	0.01	0	-9999	-10000	0	0
AKT1	0.004	0.02	-9999	-10000	0	0
FOXO1	0.021	0.028	-9999	-10000	0	0
MAPK10	-0.005	0.089	-9999	-0.25	52	52
mol:GTP	0.002	0	-9999	-10000	0	0
FOXO4	0.051	0.065	-9999	-10000	0	0
response to oxidative stress	-0.008	0.024	-9999	-10000	0	0
FOXO3A/SIRT1	-0.12	0.16	-9999	-0.48	40	40
XPO1	0.01	0	-9999	-10000	0	0
EP300	0.01	0.004	-9999	-10000	0	0
BCL2L11	0.008	0.032	-9999	-10000	0	0
FOXO1/SKP2	0.021	0.037	-9999	-0.27	2	2
mol:GDP	-0.008	0.024	-9999	-10000	0	0
RAN	0.01	0.024	-9999	-0.51	1	1
GADD45A	0.006	0.12	-9999	-0.71	2	2
YWHAQ	0.01	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.055	0.016	-9999	-10000	0	0
MST1	-0.014	0.095	-9999	-0.52	15	15
CSNK1D	0.01	0	-9999	-10000	0	0
CSNK1E	0.01	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.042	0.021	-9999	-10000	0	0
YWHAB	0.01	0	-9999	-10000	0	0
MAPK8	0.025	0.01	-9999	-10000	0	0
MAPK9	0.025	0.01	-9999	-10000	0	0
YWHAG	0.01	0	-9999	-10000	0	0
YWHAE	0.01	0	-9999	-10000	0	0
YWHAZ	0.01	0	-9999	-10000	0	0
SIRT1	0.007	0.009	-9999	-10000	0	0
SOD2	0.01	0.13	-9999	-10000	0	0
RBL2	-0.024	0.15	-9999	-0.49	4	4
RAL/GDP	0.013	0.014	-9999	-10000	0	0
CHUK	0.003	0.019	-9999	-10000	0	0
Ran/GTP	0.01	0.018	-9999	-0.37	1	1
CSNK1G2	0.01	0	-9999	-10000	0	0
RAL/GTP	0.019	0.015	-9999	-10000	0	0
CSNK1G1	0.01	0	-9999	-10000	0	0
FASLG	-0.009	0.15	-9999	-1.2	7	7
SKP2	0.005	0.048	-9999	-0.51	4	4
USP7	0.011	0.001	-9999	-10000	0	0
IKBKB	0.003	0.019	-9999	-10000	0	0
CCNB1	-0.1	0.24	-9999	-0.59	42	42
FOXO1-3a-4/beta catenin	-0.037	0.073	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.021	0.037	-9999	-0.27	2	2
CSNK1A1	0.01	0	-9999	-10000	0	0
SGK1	0.002	0.031	-9999	-0.52	1	1
CSNK1G3	0.01	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.018	0.015	-9999	-0.31	1	1
ZFAND5	0.054	0.057	-9999	-10000	0	0
SFN	0	0.072	-9999	-0.51	9	9
CDK2	0.01	0.005	-9999	-10000	0	0
FOXO3A/14-3-3	0.021	0.046	-9999	-0.37	1	1
CREBBP	0.01	0.005	-9999	-10000	0	0
FBXO32	-0.083	0.22	-9999	-0.58	38	38
BCL6	-0.024	0.15	-9999	-0.49	4	4
RALB	0.011	0	-9999	-10000	0	0
RALA	0.011	0	-9999	-10000	0	0
YWHAH	0.01	0	-9999	-10000	0	0

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.047	0.038	-10000	0	-0.44	1	1
UGCG	-0.002	0.029	-10000	0	-0.62	1	1
AKT1/mTOR/p70S6K/Hsp90/TERT	0.04	0.056	-10000	0	-0.31	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.021	0.032	-10000	0	-0.61	1	1
mol:DAG	0	0.001	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.006	0.039	-10000	0	-0.4	2	2
FRAP1	0.064	0.06	-10000	0	-0.43	3	3
FOXO3	0.066	0.053	-10000	0	-0.35	4	4
AKT1	0.062	0.056	-10000	0	-0.38	4	4
GAB2	0.006	0.047	-10000	0	-0.5	4	4
SMPD1	-0.001	0.007	-10000	0	-10000	0	0
SGMS1	-0.001	0.007	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
mol:GDP	0.018	0.015	-10000	0	-0.3	1	1
CALM1	0.01	0	-10000	0	-10000	0	0
cell proliferation	0.039	0.033	-10000	0	-0.27	3	3
EIF3A	0.01	0	-10000	0	-10000	0	0
PI3K	0.019	0.017	-10000	0	-0.35	1	1
RPS6KB1	0.022	0.021	-10000	0	-10000	0	0
mol:sphingomyelin	0	0.001	-10000	0	-10000	0	0
natural killer cell activation	0.001	0.001	-10000	0	-0.011	2	2
JAK3	0.012	0.001	-10000	0	-10000	0	0
PIK3R1	0.011	0.024	-10000	0	-0.5	1	1
JAK1	0.012	0.001	-10000	0	-10000	0	0
NFKB1	0.01	0	-10000	0	-10000	0	0
MYC	0.062	0.077	-10000	0	-0.92	2	2
MYB	0.018	0.098	-10000	0	-1.2	3	3
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.055	0.051	-10000	0	-0.38	2	2
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.031	0.019	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.055	0.05	-10000	0	-0.37	2	2
Rac1/GDP	0.022	0.013	-10000	0	-0.26	1	1
T cell proliferation	0.057	0.052	-10000	0	-0.37	2	2
SHC1	0.011	0.001	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.004	0.006	-10000	0	-0.049	6	6
PRKCZ	0.057	0.054	-10000	0	-0.38	2	2
NF kappa B1 p50/RelA	-0.004	0.038	-10000	0	-0.47	1	1
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.042	0.041	-10000	0	-0.43	2	2
HSP90AA1	0.01	0	-10000	0	-10000	0	0
RELA	0.01	0	-10000	0	-10000	0	0
IL2RA	-0.027	0.14	-10000	0	-0.51	34	34
IL2RB	0.01	0.033	-10000	0	-0.5	2	2
TERT	-0.15	0.24	-10000	0	-0.51	141	141
E2F1	0.02	0.04	-10000	0	-0.42	3	3
SOS1	0.011	0.001	-10000	0	-10000	0	0
RPS6	0.01	0	-10000	0	-10000	0	0
mol:cAMP	-0.002	0.003	0.023	6	-10000	0	6
PTPN11	0.011	0.001	-10000	0	-10000	0	0
IL2RG	0.007	0.053	-10000	0	-0.5	5	5
actin cytoskeleton organization	0.057	0.052	-10000	0	-0.37	2	2
GRB2	0.011	0.001	-10000	0	-10000	0	0
IL2	0.008	0.005	-10000	0	-10000	0	0
PIK3CA	0.012	0.001	-10000	0	-10000	0	0
Rac1/GTP	0.028	0.013	-10000	0	-0.24	1	1
LCK	0.009	0.041	-10000	0	-0.5	3	3
BCL2	0.064	0.065	-10000	0	-0.65	2	2

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.002	0.02	-9999	-10000	0	0
DAPP1	-0.002	0.11	-9999	-0.51	15	15
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.001	0.16	-9999	-0.62	21	21
mol:DAG	0.024	0.068	-9999	-0.31	8	8
HRAS	0.01	0.001	-9999	-10000	0	0
RAP1A	0.01	0.001	-9999	-10000	0	0
ARF5/GDP	0.021	0.071	-9999	-0.42	9	9
PLCG2	0.007	0.041	-9999	-0.5	3	3
PLCG1	0.01	0	-9999	-10000	0	0
ARF5	0.01	0	-9999	-10000	0	0
mol:GTP	-0.001	0.016	-9999	-10000	0	0
ARF1/GTP	-0.002	0.017	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
YES1	0.01	0	-9999	-10000	0	0
RAP1A/GTP	-0.001	0.016	-9999	-10000	0	0
ADAP1	-0.002	0.023	-9999	-0.43	1	1
ARAP3	-0.001	0.016	-9999	-10000	0	0
INPPL1	0.01	0	-9999	-10000	0	0
PREX1	0.003	0.057	-9999	-0.5	6	6
ARHGEF6	-0.008	0.093	-9999	-0.5	16	16
ARHGEF7	0.01	0	-9999	-10000	0	0
ARF1	0.01	0	-9999	-10000	0	0
NRAS	0.01	0.001	-9999	-10000	0	0
FYN	0.009	0.024	-9999	-0.5	1	1
ARF6	0.01	0	-9999	-10000	0	0
FGR	-0.029	0.14	-9999	-0.5	36	36
mol:Ca2+	0.02	0.037	-9999	-10000	0	0
mol:IP4	0	0	-9999	-10000	0	0
TIAM1	0.001	0.066	-9999	-0.5	8	8
ZAP70	0.003	0.057	-9999	-0.5	6	6
mol:IP3	0.024	0.05	-9999	-0.21	6	6
LYN	0.01	0	-9999	-10000	0	0
ARF1/GDP	0.021	0.071	-9999	-0.42	9	9
RhoA/GDP	-0.006	0.034	-9999	-0.36	2	2
PDK1/Src/Hsp90	0	0	-9999	-10000	0	0
BLNK	0.008	0.033	-9999	-0.5	2	2
actin cytoskeleton reorganization	0.04	0.062	-9999	-0.46	4	4
SRC	0.01	0	-9999	-10000	0	0
PLEKHA2	0.021	0.029	-9999	-0.29	4	4
RAC1	0.01	0	-9999	-10000	0	0
PTEN	0	0.002	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
ARF6/GTP	-0.001	0.014	-9999	-10000	0	0
RhoA/GTP	-0.001	0.015	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.001	0.12	-9999	-0.5	16	16
BLK	-0.071	0.19	-9999	-0.51	72	72
PDPK1	0.01	0	-9999	-10000	0	0
CYTH1	-0.001	0.015	-9999	-10000	0	0
HCK	-0.011	0.1	-9999	-0.5	19	19
CYTH3	-0.002	0.021	-9999	-10000	0	0
CYTH2	-0.001	0.015	-9999	-10000	0	0
KRAS	0.01	0.001	-9999	-10000	0	0
GO:0030676	0	0	-9999	-10000	0	0
FOXO3	-0.002	0.027	-9999	-0.57	1	1
SGK1	-0.002	0.03	-9999	-0.62	1	1
INPP5D	0.007	0.041	-9999	-0.5	3	3
mol:GDP	0.016	0.075	-9999	-0.44	9	9
SOS1	0.01	0	-9999	-10000	0	0
SYK	0.007	0.041	-9999	-0.5	3	3
ARF6/GDP	-0.006	0.035	-9999	-0.37	2	2
mol:PI-3-4-5-P3	-0.001	0.016	-9999	-10000	0	0
ARAP3/RAP1A/GTP	-0.001	0.016	-9999	-10000	0	0
VAV1	0.004	0.052	-9999	-0.5	5	5
mol:PI-3-4-P2	0.016	0.03	-9999	-0.35	3	3
RAS family/GTP/PI3K Class I	-0.001	0.016	-9999	-10000	0	0
PLEKHA1	0.022	0.025	-9999	-0.29	3	3
Rac1/GDP	0.021	0.071	-9999	-0.42	9	9
LAT	0.009	0.024	-9999	-0.51	1	1
Rac1/GTP	0.012	0.11	-9999	-0.47	18	18
ITK	-0.007	0.037	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.024	0.092	-9999	-0.36	17	17
LCK	0.007	0.041	-9999	-0.5	3	3
BTK	-0.015	0.059	-9999	-0.43	2	2

×

Circadian rhythm pathway

Figure S106. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S106. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	-0.022	0.077	-9999	-0.49	5	5
CLOCK	0.012	0.003	-9999	-10000	0	0
TIMELESS/CRY2	0.03	0.036	-9999	-10000	0	0
DEC1/BMAL1	0	0.001	-9999	-10000	0	0
ATR	0.01	0	-9999	-10000	0	0
NR1D1	0.032	0.021	-9999	-10000	0	0
ARNTL	0.012	0.003	-9999	-10000	0	0
TIMELESS	0.029	0.04	-9999	-10000	0	0
NPAS2	0.009	0.042	-9999	-0.51	3	3
CRY2	0.01	0	-9999	-10000	0	0
mol:CO	-0.01	0.009	-9999	-10000	0	0
CHEK1	-0.03	0.14	-9999	-0.51	36	36
mol:HEME	0.01	0.009	-9999	-10000	0	0
PER1	-0.013	0.11	-9999	-0.5	21	21
BMAL/CLOCK/NPAS2	0.031	0.027	-9999	-0.29	3	3
BMAL1/CLOCK	0.033	0.036	-9999	-10000	0	0
S phase of mitotic cell cycle	-0.022	0.077	-9999	-0.49	5	5
TIMELESS/CHEK1/ATR	-0.022	0.078	-9999	-0.5	5	5
mol:NADPH	0.01	0.009	-9999	-10000	0	0
PER1/TIMELESS	0.018	0.07	-9999	-0.52	1	1
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	0.002	0.004	-9999	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.03	0.012	-10000	0	-10000	0	0
regulation of axonogenesis	-0.023	0.004	-10000	0	-10000	0	0
myoblast fusion	0	0.01	-10000	0	-10000	0	0
mol:GTP	0	0.003	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.009	0.1	0.29	53	-10000	0	53
ARF1/GTP	0	0.001	-10000	0	-10000	0	0
mol:GM1	0.008	0.003	-10000	0	-10000	0	0
mol:Choline	0.023	0.002	-10000	0	-10000	0	0
lamellipodium assembly	0.01	0.029	-10000	0	-10000	0	0
MAPK3	0.021	0.008	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.008	0.1	-10000	0	-0.29	53	53
ARF1	0.01	0	-10000	0	-10000	0	0
ARF6/GDP	0	0.01	-10000	0	-10000	0	0
ARF1/GDP	0.026	0.016	-10000	0	-10000	0	0
ARF6	0.009	0.002	-10000	0	-10000	0	0
RAB11A	0.01	0	-10000	0	-10000	0	0
TIAM1	0.003	0.066	-10000	0	-0.5	8	8
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.021	0.008	-10000	0	-10000	0	0
actin filament bundle formation	0	0.005	-10000	0	-10000	0	0
KALRN	0.005	0.029	-10000	0	-0.26	3	3
RAB11FIP3/RAB11A	0	0	-10000	0	-10000	0	0
RhoA/GDP	0	0.005	-10000	0	-10000	0	0
NME1	-0.041	0.16	-10000	0	-0.51	47	47
Rac1/GDP	0	0.005	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0	0.003	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	0.01	0.029	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
liver development	0	0.003	-10000	0	-10000	0	0
ARF6/GTP	0	0.003	-10000	0	-10000	0	0
RhoA/GTP	0	0.001	-10000	0	-10000	0	0
mol:GDP	0.008	0.025	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	0	0.001	-10000	0	-10000	0	0
RHOA	0.01	0	-10000	0	-10000	0	0
PLD1	0.017	0.003	-10000	0	-10000	0	0
RAB11FIP3	0.01	0	-10000	0	-10000	0	0
tube morphogenesis	0.01	0.029	-10000	0	-10000	0	0
ruffle organization	0.023	0.004	-10000	0	-10000	0	0
regulation of epithelial cell migration	0	0.003	-10000	0	-10000	0	0
PLD2	0.017	0.003	-10000	0	-10000	0	0
PIP5K1A	0.023	0.004	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.023	0.002	-10000	0	-10000	0	0
Rac1/GTP	0.01	0.03	-10000	0	-10000	0	0

×

TCGA08_rtk_signaling

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
PDGFRA	0.005	0.047	-10000	0	-0.5	4	4
HRAS	0.01	0	-10000	0	-10000	0	0
EGFR	-0.006	0.088	-10000	0	-0.51	14	14
AKT	0.029	0.032	-10000	0	-0.34	3	3
FOXO3	0.01	0	-10000	0	-10000	0	0
AKT1	0.01	0	-10000	0	-10000	0	0
FOXO1	0.01	0	-10000	0	-10000	0	0
AKT3	0.007	0.041	-10000	0	-0.5	3	3
FOXO4	0.01	0	-10000	0	-10000	0	0
MET	-0.022	0.12	-10000	0	-0.51	29	29
PIK3CA	0.01	0	-10000	0	-10000	0	0
PIK3CB	0.01	0	-10000	0	-10000	0	0
NRAS	0.01	0	-10000	0	-10000	0	0
PIK3CG	-0.008	0.093	-10000	0	-0.5	16	16
PIK3R3	0.009	0.024	-10000	0	-0.5	1	1
PIK3R2	0.01	0	-10000	0	-10000	0	0
NF1	0.01	0	-10000	0	-10000	0	0
RAS	0.009	0.044	-10000	0	-0.24	4	4
ERBB2	0.006	0.042	-10000	0	-0.51	3	3
proliferation/survival/translation	-0.02	0.03	0.2	3	-10000	0	3
PI3K	0.014	0.05	-10000	0	-0.22	10	10
PIK3R1	0.009	0.024	-10000	0	-0.5	1	1
KRAS	0.01	0	-10000	0	-10000	0	0
FOXO	0.037	0.014	-10000	0	-10000	0	0
AKT2	0.01	0	-10000	0	-10000	0	0
PTEN	0.01	0	-10000	0	-10000	0	0

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.01	0	-10000	0	-10000	0	0
PTK2	0.01	0	-10000	0	-10000	0	0
CRKL	0.014	0.044	-10000	0	-0.26	11	11
GRB2/SOS1/SHC	0	0	-10000	0	-10000	0	0
HRAS	0.01	0	-10000	0	-10000	0	0
IRS1/Crk	0.014	0.044	-10000	0	-0.26	11	11
IGF-1R heterotetramer/IGF1/PTP1B	-0.007	0.044	-10000	0	-0.28	12	12
AKT1	0.03	0.04	-10000	0	-0.38	1	1
BAD	0.035	0.038	-10000	0	-0.36	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.014	0.044	-10000	0	-0.26	11	11
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.006	0.041	-10000	0	-0.26	11	11
RAF1	0.038	0.037	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.006	0.038	-10000	0	-0.44	1	1
YWHAZ	0.01	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.007	0.046	-10000	0	-0.28	12	12
PIK3CA	0.01	0	-10000	0	-10000	0	0
RPS6KB1	0.03	0.04	-10000	0	-0.38	1	1
GNB2L1	0.01	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	0.033	0.033	-10000	0	-10000	0	0
PXN	0.01	0	-10000	0	-10000	0	0
PIK3R1	0.009	0.024	-10000	0	-0.5	1	1
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
HRAS/GTP	-0.005	0.033	-10000	0	-0.39	1	1
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.005	0.033	-10000	0	-0.26	1	1
IGF-1R heterotetramer	0.007	0.035	-10000	0	-0.51	2	2
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.006	0.041	-10000	0	-0.26	11	11
Crk/p130 Cas/Paxillin	-0.006	0.037	-10000	0	-0.41	1	1
IGF1R	0.007	0.035	-10000	0	-0.51	2	2
IGF1	-0.001	0.076	-10000	0	-0.52	10	10
IRS2/Crk	0.019	0.044	-10000	0	-0.33	2	2
PI3K	-0.006	0.04	-10000	0	-0.43	1	1
apoptosis	-0.037	0.034	0.31	1	-10000	0	1
HRAS/GDP	0	0	-10000	0	-10000	0	0
PRKCD	0.025	0.056	-10000	0	-0.33	11	11
RAF1/14-3-3 E	0.04	0.033	-10000	0	-10000	0	0
BAD/14-3-3	0.039	0.036	-10000	0	-0.33	1	1
PRKCZ	0.028	0.044	-10000	0	-0.38	1	1
Crk/p130 Cas/Paxillin/FAK1	-0.005	0.029	-10000	0	-0.32	1	1
PTPN1	0.01	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.02	0.058	-10000	0	-0.35	11	11
BCAR1	0.009	0.024	-10000	0	-0.5	1	1
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.006	0.037	-10000	0	-0.24	11	11
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.01	0	-10000	0	-10000	0	0
IRS1/NCK2	0.014	0.044	-10000	0	-0.26	11	11
GRB10	0.01	0	-10000	0	-10000	0	0
PTPN11	0.014	0.044	-10000	0	-0.26	11	11
IRS1	0.008	0.048	-10000	0	-0.28	12	12
IRS2	0.014	0.046	-10000	0	-0.26	12	12
IGF-1R heterotetramer/IGF1	-0.01	0.059	-10000	0	-0.37	12	12
GRB2	0.01	0	-10000	0	-10000	0	0
PDPK1	0.025	0.042	-10000	0	-0.41	1	1
YWHAE	0.01	0	-10000	0	-10000	0	0
PRKD1	0.014	0.079	-10000	0	-0.37	11	11
SHC1	0.01	0	-10000	0	-10000	0	0

×

S1P3 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.009	0.024	-9999	-0.5	1	1
mol:S1P	0.001	0.002	-9999	-10000	0	0
S1P1/S1P/Gi	0.002	0.078	-9999	-0.23	43	43
GNAO1	0.006	0.054	-9999	-0.51	5	5
S1P/S1P3/G12/G13	-0.001	0.013	-9999	-0.27	1	1
AKT1	-0.008	0.036	-9999	-0.62	1	1
AKT3	0.023	0.1	-9999	-1.1	3	3
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.009	0.024	-9999	-0.5	1	1
GNAI2	0.011	0.002	-9999	-10000	0	0
GNAI3	0.011	0.002	-9999	-10000	0	0
GNAI1	0.009	0.033	-9999	-0.5	2	2
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.01	0.024	-9999	-0.51	1	1
S1PR2	0.01	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.012	0.073	-9999	-0.35	4	4
MAPK3	0.018	0.069	-9999	-0.45	2	2
MAPK1	0.018	0.069	-9999	-0.45	2	2
JAK2	0.021	0.07	-9999	-0.4	3	3
CXCR4	0.018	0.069	-9999	-0.45	2	2
FLT1	0.012	0.003	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.018	0.069	-9999	-0.45	2	2
S1P/S1P3/Gi	0.012	0.073	-9999	-0.35	4	4
RAC1	0.01	0	-9999	-10000	0	0
RhoA/GTP	-0.018	0.055	-9999	-0.43	2	2
VEGFA	0.012	0.003	-9999	-10000	0	0
S1P/S1P2/Gi	0.01	0.07	-9999	-0.35	3	3
VEGFR1 homodimer/VEGFA homodimer	0.021	0.005	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
S1P/S1P3/Gq	0.016	0.053	-9999	-0.25	16	16
GNAQ	0.009	0.024	-9999	-0.5	1	1
GNAZ	-0.034	0.14	-9999	-0.5	41	41
G12/G13	0	0	-9999	-10000	0	0
GNA14	-0.005	0.087	-9999	-0.5	14	14
GNA15	0.01	0	-9999	-10000	0	0
GNA12	0.01	0	-9999	-10000	0	0
GNA13	0.01	0	-9999	-10000	0	0
GNA11	0.008	0.033	-9999	-0.5	2	2
Rac1/GTP	-0.018	0.055	-9999	-0.43	2	2

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.004	0.053	-10000	0	-0.5	5	5
positive regulation of NF-kappaB transcription factor activity	-0.005	0.047	-10000	0	-0.4	6	6
MAP2K4	0.035	0.027	-10000	0	-0.33	1	1
IKBKB	0.01	0	-10000	0	-10000	0	0
TNFRSF10B	0.01	0	-10000	0	-10000	0	0
TNFRSF10A	0.008	0.033	-10000	0	-0.5	2	2
SMPD1	-0.002	0.019	-10000	0	-0.19	4	4
IKBKG	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.008	0.033	-10000	0	-0.5	2	2
TRAIL/TRAILR2	-0.004	0.037	-10000	0	-0.36	5	5
TRAIL/TRAILR3	-0.009	0.062	-10000	0	-0.42	10	10
TRAIL/TRAILR1	-0.005	0.047	-10000	0	-0.4	6	6
TRAIL/TRAILR4	-0.005	0.047	-10000	0	-0.4	6	6
TRAIL/TRAILR1/DAP3/GTP	-0.004	0.037	-10000	0	-0.31	6	6
IKK complex	-0.001	0.013	-10000	0	-10000	0	0
RIPK1	0.01	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0	0	-10000	0	-10000	0	0
MAPK3	0.014	0.038	-10000	0	-0.36	5	5
MAP3K1	-0.003	0.025	-10000	0	-0.36	1	1
TRAILR4 (trimer)	0.008	0.033	-10000	0	-0.5	2	2
TRADD	0.01	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.008	0.033	-10000	0	-0.5	2	2
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.026	0.033	-10000	0	-0.46	1	1
CFLAR	0.01	0	-10000	0	-10000	0	0
MAPK1	0.014	0.038	-10000	0	-0.36	5	5
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.004	0.033	-10000	0	-0.49	1	1
mol:ceramide	-0.002	0.019	-10000	0	-0.19	4	4
FADD	0.01	0	-10000	0	-10000	0	0
MAPK8	0.039	0.026	-10000	0	-0.31	1	1
TRAF2	0.01	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.002	0.062	-10000	0	-0.5	7	7
CHUK	0.01	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.004	0.04	-10000	0	-0.34	6	6
DAP3	0.01	0	-10000	0	-10000	0	0
CASP10	-0.004	0.044	0.24	1	-0.37	5	6
JNK cascade	-0.005	0.047	-10000	0	-0.4	6	6
TRAIL (trimer)	0.004	0.053	-10000	0	-0.5	5	5
TNFRSF10C	0.002	0.062	-10000	0	-0.5	7	7
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.004	0.034	-10000	0	-0.37	2	2
TRAIL/TRAILR2/FADD	-0.003	0.03	-10000	0	-0.29	5	5
cell death	-0.002	0.019	-10000	0	-0.19	4	4
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.027	0.024	-10000	0	-10000	0	0
TRAILR2 (trimer)	0.01	0	-10000	0	-10000	0	0
CASP8	-0.001	0.041	-10000	0	-0.86	1	1
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.003	0.024	-10000	0	-10000	0	0

×

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

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
BAG4	0.009	0.024	-9999	-0.51	1	1
Caspase 8 (4 units)	-0.006	0.039	-9999	-0.34	4	4
NEF	0.002	0.021	-9999	-10000	0	0
NFKBIA	0.011	0.011	-9999	-10000	0	0
BIRC3	0.029	0.058	-9999	-0.48	6	6
CYCS	0.036	0.044	-9999	-0.3	4	4
RIPK1	0.01	0	-9999	-10000	0	0
CD247	0.005	0.063	-9999	-0.52	6	6
MAP2K7	0.036	0.037	-9999	-0.33	1	1
protein ubiquitination	0.05	0.033	-9999	-10000	0	0
CRADD	0.009	0.024	-9999	-0.51	1	1
DAXX	0.01	0	-9999	-10000	0	0
FAS	0.005	0.047	-9999	-0.5	4	4
BID	0.031	0.046	-9999	-0.32	4	4
NF-kappa-B/RelA/I kappa B alpha	-0.003	0.027	-9999	-10000	0	0
TRADD	0.01	0	-9999	-10000	0	0
MAP3K5	0.01	0	-9999	-10000	0	0
CFLAR	0.01	0	-9999	-10000	0	0
FADD	0.01	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.003	0.027	-9999	-10000	0	0
MAPK8	0.041	0.036	-9999	-10000	0	0
APAF1	0.01	0	-9999	-10000	0	0
TRAF1	0.01	0	-9999	-10000	0	0
TRAF2	0.01	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.025	0.048	-9999	-0.29	10	10
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.043	0.039	-9999	-10000	0	0
CHUK	0.051	0.035	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.003	0.029	-9999	-0.49	1	1
TCRz/NEF	-0.009	0.056	-9999	-0.34	12	12
TNF	-0.011	0.1	-9999	-0.5	19	19
FASLG	0.01	0.083	-9999	-0.47	12	12
NFKB1	0.011	0.011	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.013	0.059	-9999	-0.29	20	20
CASP6	-0.004	0.035	-9999	-0.6	1	1
CASP7	0.061	0.057	-9999	-0.48	3	3
RELA	0.011	0.011	-9999	-10000	0	0
CASP2	0.01	0	-9999	-10000	0	0
CASP3	0.061	0.057	-9999	-0.48	3	3
TNFRSF1A	0.01	0	-9999	-10000	0	0
TNFR1A/BAG4	-0.001	0.017	-9999	-0.36	1	1
CASP8	0.009	0.024	-9999	-0.5	1	1
CASP9	0.01	0	-9999	-10000	0	0
MAP3K14	0.048	0.037	-9999	-10000	0	0
APAF-1/Caspase 9	-0.007	0.042	-9999	-0.48	1	1
BCL2	0.044	0.042	-9999	-0.37	1	1

×

E-cadherin signaling in the nascent adherens junction

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.031	0.03	-9999	-0.42	2	2
KLHL20	-0.012	0.034	-9999	-0.25	2	2
CYFIP2	0.003	0.057	-9999	-0.5	6	6
Rac1/GDP	0.05	0.021	-9999	-10000	0	0
ENAH	0.031	0.03	-9999	-0.42	2	2
AP1M1	0.01	0	-9999	-10000	0	0
RAP1B	0.01	0	-9999	-10000	0	0
RAP1A	0.01	0	-9999	-10000	0	0
CTNNB1	0.01	0	-9999	-10000	0	0
CDC42/GTP	-0.001	0.011	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.009	0.024	-9999	-0.17	2	2
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.002	0.021	-9999	-0.26	3	3
RAPGEF1	0.041	0.026	-9999	-0.35	2	2
CTNND1	0.01	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.002	0.028	-9999	-0.43	2	2
CRK	0.037	0.028	-9999	-0.39	2	2
E-cadherin/gamma catenin/alpha catenin	-0.002	0.024	-9999	-0.3	3	3
alphaE/beta7 Integrin	-0.001	0.016	-9999	-0.35	1	1
IQGAP1	0.01	0	-9999	-10000	0	0
NCKAP1	0.01	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0	0	-9999	-10000	0	0
DLG1	0.031	0.03	-9999	-0.42	2	2
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.009	-9999	-10000	0	0
MLLT4	0.01	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.032	0.091	-9999	-0.28	53	53
PI3K	-0.001	0.011	-9999	-10000	0	0
ARF6	0.01	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.002	0.028	-9999	-0.36	3	3
TIAM1	0.001	0.066	-9999	-0.5	8	8
E-cadherin(dimer)/Ca2+	-0.001	0.016	-9999	-10000	0	0
AKT1	-0.001	0.007	-9999	-10000	0	0
PIK3R1	0.009	0.024	-9999	-0.5	1	1
CDH1	0.008	0.033	-9999	-0.5	2	2
RhoA/GDP	0.049	0.021	-9999	-10000	0	0
actin cytoskeleton organization	-0.009	0.025	-9999	-0.18	2	2
CDC42/GDP	0.049	0.021	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.018	0.018	-9999	-0.23	2	2
ITGB7	0.009	0.024	-9999	-0.5	1	1
RAC1	0.01	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.001	0.017	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.001	0.016	-9999	-0.25	2	2
mol:GDP	0.048	0.023	-9999	-0.28	2	2
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	0.009	0.024	-9999	-0.51	1	1
p120 catenin/RhoA/GDP	-0.001	0.016	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0	0	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
CDC42	0.01	0	-9999	-10000	0	0
CTNNA1	0.01	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.018	0.034	-9999	-0.21	6	6
NME1	-0.043	0.16	-9999	-0.51	47	47
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.031	0.03	-9999	-0.42	2	2
regulation of cell-cell adhesion	-0.001	0.009	-9999	-10000	0	0
WASF2	-0.004	0.012	-9999	-10000	0	0
Rap1/GTP	-0.001	0.012	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.002	0.022	-9999	-10000	0	0
CCND1	0.021	0.042	-9999	-0.26	6	6
VAV2	0.038	0.042	-9999	-0.47	3	3
RAP1/GDP	0	0.014	-9999	-10000	0	0
adherens junction assembly	0.031	0.028	-9999	-0.4	2	2
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.01	0	-9999	-10000	0	0
PIP5K1C	0.01	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.002	0.02	-9999	-10000	0	0
E-cadherin/beta catenin	-0.001	0.022	-9999	-0.34	2	2
mol:GTP	0	0	-9999	-10000	0	0
SRC	0.032	0.03	-9999	-0.42	2	2
PIK3CA	0.01	0	-9999	-10000	0	0
Rac1/GTP	-0.018	0.053	-9999	-0.42	2	2
E-cadherin/beta catenin/alpha catenin	-0.001	0.019	-9999	-0.29	2	2
ITGAE	0.01	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.002	0.029	-9999	-0.44	2	2

×

Rapid glucocorticoid signaling

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
Gs family/GDP/Gbeta gamma	-0.007	0.041	-10000	0	-0.25	13	13
MAPK9	0.007	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	0.001	0.03	-10000	0	-0.37	3	3
GNB1/GNG2	-0.001	0.019	-10000	0	-0.3	2	2
GNB1	0.01	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.007	0	-10000	0	-10000	0	0
Gs family/GTP	-0.007	0.042	-10000	0	-0.28	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	0.002	0.011	0.075	11	-10000	0	11
GNAL	-0.002	0.078	-10000	0	-0.5	11	11
GNG2	0.008	0.033	-10000	0	-0.5	2	2
CRH	0	0.041	-10000	0	-0.51	3	3
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.007	0	-10000	0	-10000	0	0
MAPK11	0.005	0.026	-10000	0	-0.32	3	3

×

PDGFR-beta signaling pathway

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
S1P1/Sphingosine-1-phosphate	-0.003	0.035	-9999	-0.55	1	1
PDGFB-D/PDGFRB/SLAP	-0.01	0.062	-9999	-0.38	12	12
PDGFB-D/PDGFRB/APS/CBL	-0.001	0.019	-9999	-0.29	2	2
AKT1	0.044	0.031	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.024	0.042	-9999	-0.59	1	1
PIK3CA	0.01	0	-9999	-10000	0	0
FGR	-0.037	0.14	-9999	-0.51	36	36
mol:Ca2+	0.022	0.039	-9999	-0.63	1	1
MYC	0.032	0.071	-9999	-0.68	3	3
SHC1	0.01	0	-9999	-10000	0	0
HRAS/GDP	0.002	0.013	-9999	-10000	0	0
LRP1/PDGFRB/PDGFB	-0.007	0.057	-9999	-0.4	8	8
GRB10	0.01	0	-9999	-10000	0	0
PTPN11	0.01	0	-9999	-10000	0	0
GO:0007205	0.022	0.04	-9999	-0.65	1	1
PTEN	0.01	0	-9999	-10000	0	0
GRB2	0.01	0	-9999	-10000	0	0
GRB7	0.003	0.058	-9999	-0.51	6	6
PDGFB-D/PDGFRB/SHP2	0	0.017	-9999	-0.36	1	1
PDGFB-D/PDGFRB/GRB10	0	0.017	-9999	-0.36	1	1
cell cycle arrest	-0.01	0.062	-9999	-0.38	12	12
HRAS	0.01	0	-9999	-10000	0	0
HIF1A	0.048	0.029	-9999	-10000	0	0
GAB1	0.02	0.05	-9999	-0.64	1	1
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.024	0.046	-9999	-0.57	1	1
PDGFB-D/PDGFRB	0.005	0.018	-9999	-0.31	1	1
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0	0.017	-9999	-0.36	1	1
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.004	0.035	-9999	-0.51	1	1
positive regulation of MAPKKK cascade	0	0.017	-9999	-0.36	1	1
PIK3R1	0.009	0.024	-9999	-0.5	1	1
mol:IP3	0.022	0.04	-9999	-0.65	1	1
E5	0	0.001	-9999	-10000	0	0
CSK	0.009	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.005	0.044	-9999	-0.36	7	7
SHB	0.009	0.024	-9999	-0.5	1	1
BLK	-0.015	0.054	-9999	-0.47	5	5
PTPN2	0.01	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0	0.017	-9999	-0.36	1	1
BCAR1	0.009	0.024	-9999	-0.5	1	1
VAV2	0.021	0.066	-9999	-0.55	2	2
CBL	0.01	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0	0.017	-9999	-0.36	1	1
LCK	-0.001	0.037	-9999	-0.45	3	3
PDGFRB	0.01	0.024	-9999	-0.51	1	1
ACP1	0.01	0	-9999	-10000	0	0
HCK	-0.019	0.11	-9999	-0.54	19	19
ABL1	0.018	0.051	-9999	-0.6	1	1
PDGFB-D/PDGFRB/CBL	0.019	0.056	-9999	-0.73	1	1
PTPN1	0.01	0.001	-9999	-10000	0	0
SNX15	0.01	0	-9999	-10000	0	0
STAT3	0.01	0	-9999	-10000	0	0
STAT1	0.01	0	-9999	-10000	0	0
cell proliferation	0.032	0.065	-9999	-0.6	3	3
SLA	-0.003	0.081	-9999	-0.5	12	12
actin cytoskeleton reorganization	0.039	0.021	-9999	-10000	0	0
SRC	0.002	0.018	-9999	-0.34	1	1
PI3K	-0.004	0.027	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	-0.004	0.036	-9999	-0.3	7	7
SH2B2	0.009	0.024	-9999	-0.5	1	1
PLCgamma1/SPHK1	0.025	0.044	-9999	-0.62	1	1
LYN	0.003	0.018	-9999	-0.34	1	1
LRP1	0.005	0.047	-9999	-0.5	4	4
SOS1	0.01	0	-9999	-10000	0	0
STAT5B	0.01	0	-9999	-10000	0	0
STAT5A	0.009	0.024	-9999	-0.5	1	1
NCK1-2/p130 Cas	0.002	0.018	-9999	-10000	0	0
SPHK1	0.006	0.048	-9999	-0.51	4	4
EDG1	0.001	0.001	-9999	-10000	0	0
mol:DAG	0.022	0.04	-9999	-0.65	1	1
PLCG1	0.022	0.041	-9999	-0.67	1	1
NHERF/PDGFRB	-0.005	0.038	-9999	-0.3	8	8
YES1	0.002	0.017	-9999	-0.34	1	1
cell migration	-0.005	0.038	-9999	-0.3	8	8
SHC/Grb2/SOS1	0.002	0.014	-9999	-10000	0	0
SLC9A3R2	0.004	0.052	-9999	-0.5	5	5
SLC9A3R1	0.008	0.034	-9999	-0.51	2	2
NHERF1-2/PDGFRB/PTEN	-0.004	0.034	-9999	-0.26	3	3
FYN	0.001	0.03	-9999	-0.43	2	2
DOK1	0.026	0.014	-9999	-0.27	1	1
HRAS/GTP	0	0	-9999	-10000	0	0
PDGFB	0.003	0.057	-9999	-0.5	6	6
RAC1	0.029	0.067	-9999	-0.53	3	3
PRKCD	0.027	0.014	-9999	-0.27	1	1
FER	0.027	0.014	-9999	-0.27	1	1
MAPKKK cascade	0	0.01	-9999	-10000	0	0
RASA1	0.027	0.014	-9999	-0.27	1	1
NCK1	0.01	0	-9999	-10000	0	0
NCK2	0.01	0	-9999	-10000	0	0
p62DOK/Csk	0.007	0.017	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHB	-0.001	0.023	-9999	-0.36	2	2
chemotaxis	0.018	0.05	-9999	-0.58	1	1
STAT1-3-5/STAT1-3-5	-0.001	0.014	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	-0.001	0.017	-9999	-0.37	1	1
PTPRJ	0.01	0	-9999	-10000	0	0

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.066	0.012	-9999	-10000	0	0
ERC1	0.01	0	-9999	-10000	0	0
RIP2/NOD2	-0.001	0.016	-9999	-0.35	1	1
NFKBIA	0.037	0	-9999	-10000	0	0
BIRC2	0.01	0	-9999	-10000	0	0
IKBKB	0.01	0	-9999	-10000	0	0
RIPK2	0.01	0	-9999	-10000	0	0
IKBKG	0	0.008	-9999	-10000	0	0
IKK complex/A20	-0.008	0.038	-9999	-10000	0	0
NEMO/A20/RIP2	0.01	0	-9999	-10000	0	0
XPO1	0.01	0	-9999	-10000	0	0
NEMO/ATM	0.04	0.01	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.009	0.024	-9999	-0.51	1	1
Exportin 1/RanGTP	-0.001	0.014	-9999	-0.31	1	1
IKK complex/ELKS	0	0.007	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0	0	-9999	-10000	0	0
NOD2	0.009	0.024	-9999	-0.5	1	1
NFKB1	0.013	0	-9999	-10000	0	0
RELA	0.013	0	-9999	-10000	0	0
MALT1	0.01	0	-9999	-10000	0	0
cIAP1/UbcH5C	0	0	-9999	-10000	0	0
ATM	0.01	0	-9999	-10000	0	0
TNF/TNFR1A	-0.014	0.07	-9999	-0.35	19	19
TRAF6	0.01	0	-9999	-10000	0	0
PRKCA	0.008	0.033	-9999	-0.5	2	2
CHUK	0.01	0	-9999	-10000	0	0
UBE2D3	0.01	0	-9999	-10000	0	0
TNF	-0.011	0.1	-9999	-0.5	19	19
NF kappa B1 p50/RelA	0	0	-9999	-10000	0	0
BCL10	0.01	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.037	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.013	0	-9999	-10000	0	0
TNFRSF1A	0.01	0	-9999	-10000	0	0
IKK complex	0	0.007	-9999	-10000	0	0
CYLD	0.01	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.001	0.014	-9999	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.01	0	-9999	-10000	0	0
ITGB7	0.009	0.024	-9999	-0.5	1	1
ITGA4	0.008	0.033	-9999	-0.5	2	2
alpha4/beta7 Integrin	-0.002	0.028	-9999	-0.35	3	3
alpha4/beta1 Integrin	-0.002	0.023	-9999	-0.35	2	2

×

Paxillin-independent events mediated by a4b1 and a4b7

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.022	0.027	-9999	-0.31	3	3
CRKL	0.01	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0.01	0	-9999	-10000	0	0
ITGA4	0.008	0.033	-9999	-0.5	2	2
alpha4/beta7 Integrin/MAdCAM1	-0.005	0.036	-9999	-0.26	9	9
EPO	0.003	0.042	-9999	-0.51	3	3
alpha4/beta7 Integrin	-0.002	0.028	-9999	-0.35	3	3
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.002	0.023	-9999	-0.35	2	2
EPO/EPOR (dimer)	-0.002	0.029	-9999	-0.36	3	3
lamellipodium assembly	0	0.012	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
PI3K	-0.001	0.016	-9999	-0.35	1	1
ARF6	0.01	0	-9999	-10000	0	0
JAK2	0.005	0.027	-9999	-0.32	1	1
PXN	0.01	0	-9999	-10000	0	0
PIK3R1	0.009	0.024	-9999	-0.5	1	1
MADCAM1	0.002	0.059	-9999	-0.51	6	6
cell adhesion	-0.005	0.036	-9999	-0.26	9	9
CRKL/CBL	0	0	-9999	-10000	0	0
ITGB1	0.01	0	-9999	-10000	0	0
SRC	0.023	0.032	-9999	-0.26	6	6
ITGB7	0.009	0.024	-9999	-0.5	1	1
RAC1	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.004	0.033	-9999	-0.29	6	6
p130Cas/Crk/Dock1	0.037	0.03	-9999	-10000	0	0
VCAM1	0.005	0.047	-9999	-0.5	4	4
RHOA	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.001	0.017	-9999	-0.26	2	2
BCAR1	0.028	0.032	-9999	-10000	0	0
EPOR	0.01	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.01	0	-9999	-10000	0	0
GIT1	0.01	0	-9999	-10000	0	0
Rac1/GTP	0	0.012	-9999	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.033	0.042	-10000	0	-10000	0	0
BAG4	0.009	0.024	-10000	0	-0.51	1	1
BAD	0.024	0.018	-10000	0	-10000	0	0
NFKBIA	0.01	0	-10000	0	-10000	0	0
BIRC3	0.003	0.058	-10000	0	-0.51	6	6
BAX	0.024	0.018	-10000	0	-10000	0	0
EnzymeConsortium:3.1.4.12	0.011	0.013	-10000	0	-10000	0	0
IKBKB	0.038	0.041	-10000	0	-10000	0	0
MAP2K2	0.033	0.02	-10000	0	-10000	0	0
MAP2K1	0.033	0.02	-10000	0	-10000	0	0
SMPD1	0.015	0.013	-10000	0	-10000	0	0
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.038	0.044	-10000	0	-10000	0	0
MAP2K4	0.029	0.018	-10000	0	-10000	0	0
protein ubiquitination	0.039	0.041	-10000	0	-10000	0	0
EnzymeConsortium:2.7.1.37	0.036	0.023	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.029	0.02	-10000	0	-10000	0	0
CRADD	0.009	0.024	-10000	0	-0.51	1	1
mol:ceramide	0.018	0.019	-10000	0	-10000	0	0
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-10000	0	-10000	0	0
MADD	0.01	0	-10000	0	-10000	0	0
MAP3K1	0.024	0.018	-10000	0	-10000	0	0
TRADD	0.01	0	-10000	0	-10000	0	0
RELA/p50	0.01	0	-10000	0	-10000	0	0
MAPK3	0.035	0.02	-10000	0	-10000	0	0
MAPK1	0.035	0.02	-10000	0	-10000	0	0
p50/RELA/I-kappa-B-alpha	0	0	-10000	0	-10000	0	0
FADD	0.033	0.042	-10000	0	-10000	0	0
KSR1	0.024	0.019	-10000	0	-10000	0	0
MAPK8	0.033	0.018	-10000	0	-10000	0	0
TRAF2	0.01	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	0.038	0.041	-10000	0	-10000	0	0
TNF R/SODD	-0.001	0.017	-10000	0	-0.36	1	1
TNF	-0.011	0.1	-10000	0	-0.5	19	19
CYCS	0.025	0.018	0.13	1	-10000	0	1
IKBKG	0.038	0.041	-10000	0	-10000	0	0
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.028	0.044	-10000	0	-10000	0	0
RELA	0.01	0	-10000	0	-10000	0	0
RIPK1	0.01	0	-10000	0	-10000	0	0
AIFM1	0.025	0.018	0.13	1	-10000	0	1
TNF/TNF R/SODD	-0.013	0.059	-10000	0	-0.29	20	20
TNFRSF1A	0.01	0	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.021	0.035	-10000	0	-0.68	1	1
NSMAF	0.033	0.042	-10000	0	-10000	0	0
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
BCL2	0.007	0.041	-10000	0	-0.51	3	3

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.002	0.024	-9999	-0.3	3	3
E-cadherin/beta catenin	-0.002	0.023	-9999	-0.35	2	2
CTNNB1	0.01	0	-9999	-10000	0	0
JUP	0.009	0.024	-9999	-0.51	1	1
CDH1	0.008	0.033	-9999	-0.5	2	2

×

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.01	0	-9999	-10000	0	0
SMAD2	0.011	0	-9999	-10000	0	0
SMAD3	0.033	0	-9999	-10000	0	0
SMAD3/SMAD4	0.036	0.008	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	0	0	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	-0.003	0.027	-9999	-10000	0	0
PPM1A	0.01	0	-9999	-10000	0	0
CALM1	0.01	0	-9999	-10000	0	0
SMAD2/SMAD4	0.016	0	-9999	-10000	0	0
MAP3K1	0.01	0	-9999	-10000	0	0
TRAP-1/SMAD4	-0.002	0.023	-9999	-0.35	2	2
MAPK3	0.01	0	-9999	-10000	0	0
MAPK1	0.01	0	-9999	-10000	0	0
NUP214	0.01	0	-9999	-10000	0	0
CTDSP1	0.01	0	-9999	-10000	0	0
CTDSP2	0.01	0	-9999	-10000	0	0
CTDSPL	0.01	0	-9999	-10000	0	0
KPNB1	0.01	0	-9999	-10000	0	0
TGFBRAP1	0.008	0.033	-9999	-0.5	2	2
UBE2I	0.01	0	-9999	-10000	0	0
NUP153	0.01	0	-9999	-10000	0	0
KPNA2	0.002	0.064	-9999	-0.51	7	7
PIAS4	0.01	0	-9999	-10000	0	0

×

EPO signaling 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.06	0.029	-10000	0	-10000	0	0
CRKL	0.035	0.027	-10000	0	-10000	0	0
mol:DAG	0.04	0.022	-10000	0	-10000	0	0
HRAS	0.052	0.026	-10000	0	-10000	0	0
MAPK8	0.027	0.022	-10000	0	-10000	0	0
RAP1A	0.035	0.027	-10000	0	-10000	0	0
GAB1	0.035	0.029	-10000	0	-10000	0	0
MAPK14	0.027	0.022	-10000	0	-10000	0	0
EPO	0.006	0.041	-10000	0	-0.51	3	3
PLCG1	0.041	0.023	-10000	0	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0.012	0.003	-10000	0	-10000	0	0
RAPGEF1	0.01	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.005	0.036	-10000	0	-0.3	7	7
GAB1/SHC/GRB2/SOS1	-0.003	0.02	-10000	0	-10000	0	0
EPO/EPOR (dimer)	0.015	0.03	-10000	0	-0.36	3	3
IRS2	0.035	0.033	-10000	0	-0.43	1	1
STAT1	0.048	0.025	-10000	0	-10000	0	0
STAT5B	0.044	0.024	-10000	0	-10000	0	0
cell proliferation	0.032	0.02	-10000	0	-10000	0	0
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.004	0.028	-10000	0	-0.37	1	1
TEC	0.035	0.027	-10000	0	-10000	0	0
SOCS3	0.005	0.047	-10000	0	-0.5	4	4
STAT1 (dimer)	0.048	0.025	-10000	0	-10000	0	0
JAK2	0.01	0.024	-10000	0	-0.5	1	1
PIK3R1	0.009	0.024	-10000	0	-0.5	1	1
EPO/EPOR (dimer)/JAK2	0.04	0.029	-10000	0	-10000	0	0
EPO/EPOR	0.015	0.03	-10000	0	-0.36	3	3
LYN	0.011	0.001	-10000	0	-10000	0	0
TEC/VAV2	0.041	0.029	-10000	0	-10000	0	0
elevation of cytosolic calcium ion concentration	0.012	0.003	-10000	0	-10000	0	0
SHC1	0.01	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	0.026	0.025	-10000	0	-0.28	3	3
mol:IP3	0.04	0.022	-10000	0	-10000	0	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.005	0.034	-10000	0	-0.4	2	2
SH2B3	0.009	0.033	-10000	0	-0.5	2	2
NFKB1	0.027	0.022	-10000	0	-10000	0	0
EPO/EPOR (dimer)/JAK2/SOCS3	-0.002	0.03	0.24	2	-0.25	1	3
PTPN6	0.03	0.028	-10000	0	-10000	0	0
TEC/VAV2/GRB2	0.044	0.028	-10000	0	-10000	0	0
EPOR	0.012	0.003	-10000	0	-10000	0	0
INPP5D	0.007	0.041	-10000	0	-0.5	3	3
mol:GDP	-0.003	0.02	-10000	0	-10000	0	0
SOS1	0.01	0	-10000	0	-10000	0	0
PLCG2	0.007	0.041	-10000	0	-0.5	3	3
CRKL/CBL/C3G	0.044	0.025	-10000	0	-10000	0	0
VAV2	0.035	0.029	-10000	0	-10000	0	0
CBL	0.035	0.027	-10000	0	-10000	0	0
SHC/Grb2/SOS1	-0.002	0.019	-10000	0	-10000	0	0
STAT5A	0.044	0.033	-10000	0	-0.49	1	1
GRB2	0.01	0	-10000	0	-10000	0	0
STAT5 (dimer)	0.058	0.036	-10000	0	-0.44	1	1
LYN/PLCgamma2	-0.002	0.028	-10000	0	-0.35	3	3
PTPN11	0.01	0	-10000	0	-10000	0	0
BTK	0.019	0.073	-10000	0	-0.41	4	4
BCL2	0.058	0.051	-10000	0	-0.81	1	1

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.004	0.029	-10000	0	-0.29	3	3
CaM/Ca2+	0	0	-10000	0	-10000	0	0
AKT1	0.01	0	-10000	0	-10000	0	0
AKT2	0.01	0	-10000	0	-10000	0	0
STXBP4	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.031	0.038	0.2	1	-0.32	3	4
YWHAZ	0.01	0	-10000	0	-10000	0	0
CALM1	0.01	0	-10000	0	-10000	0	0
YWHAQ	0.01	0	-10000	0	-10000	0	0
TBC1D4	0.018	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.01	0	-10000	0	-10000	0	0
YWHAB	0.01	0	-10000	0	-10000	0	0
SNARE/Synip	0	0	-10000	0	-10000	0	0
YWHAG	0.01	0	-10000	0	-10000	0	0
ASIP	0.005	0.024	-10000	0	-0.51	1	1
PRKCI	0.01	0	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0	0	-10000	0	-10000	0	0
RHOQ	0.01	0	-10000	0	-10000	0	0
GYS1	0.025	0	-10000	0	-10000	0	0
PRKCZ	0.007	0.041	-10000	0	-0.5	3	3
TRIP10	0.01	0	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-10000	0	-10000	0	0
AS160/14-3-3	0.035	0.018	-10000	0	-10000	0	0
VAMP2	0.01	0	-10000	0	-10000	0	0
SLC2A4	0.032	0.041	0.21	1	-0.36	3	4
STX4	0.01	0	-10000	0	-10000	0	0
GSK3B	0.02	0	-10000	0	-10000	0	0
SFN	0	0.072	-10000	0	-0.51	9	9
LNPEP	0.01	0	-10000	0	-10000	0	0
YWHAE	0.01	0	-10000	0	-10000	0	0

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.01	0	-10000	0	-10000	0	0
mol:PIP3	-0.001	0.016	-10000	0	-0.25	2	2
FRAP1	0.012	0.006	-10000	0	-10000	0	0
AKT1	-0.001	0.014	-10000	0	-0.22	1	1
INSR	0.01	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.011	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0	0.004	-10000	0	-10000	0	0
TSC2	0.01	0	-10000	0	-10000	0	0
RHEB/GDP	-0.001	0.013	-10000	0	-10000	0	0
TSC1	0.01	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.012	0.015	-10000	0	-0.32	1	1
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0	0.005	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.01	0	-10000	0	-10000	0	0
RPS6KB1	0.022	0.01	-10000	0	-10000	0	0
MAP3K5	0.008	0	-10000	0	-10000	0	0
PIK3R1	0.009	0.024	-10000	0	-0.5	1	1
apoptosis	0.008	0	-10000	0	-10000	0	0
mol:LY294002	0	0	-10000	0	-0.001	1	1
EIF4B	0.026	0.009	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0	0.007	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	0	0.002	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.018	0.019	-10000	0	-0.26	2	2
mTOR/RHEB/GTP/Raptor/GBL	0.025	0.009	-10000	0	-10000	0	0
FKBP1A	0.01	0	-10000	0	-10000	0	0
RHEB/GTP	-0.001	0.013	-10000	0	-10000	0	0
mol:Amino Acids	0	0	-10000	0	-0.001	1	1
FKBP12/Rapamycin	0	0	-10000	0	-10000	0	0
PDPK1	-0.001	0.015	-10000	0	-0.24	1	1
EIF4E	0.01	0	-10000	0	-10000	0	0
ASK1/PP5C	0.017	0.003	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.013	0.006	-10000	0	-10000	0	0
TSC1/TSC2	-0.001	0.012	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	0.001	1	-10000	0	1
RPS6	0.01	0	-10000	0	-10000	0	0
PPP5C	0.01	0	-10000	0	-10000	0	0
EIF4G1	0.01	0	-10000	0	-10000	0	0
IRS1	0.006	0.017	-10000	0	-0.35	1	1
INS	0	0	-10000	0	-10000	0	0
PTEN	0.009	0	-10000	0	-10000	0	0
PDK2	-0.001	0.015	-10000	0	-0.24	1	1
EIF4EBP1	0.007	0.011	-10000	0	-10000	0	0
PIK3CA	0.01	0	-10000	0	-10000	0	0
PPP2R5D	0.017	0.005	-10000	0	-10000	0	0
peptide biosynthetic process	0.014	0	-10000	0	-10000	0	0
RHEB	0.009	0.024	-10000	0	-0.51	1	1
EIF4A1	0.01	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	-10000	0	-10000	0	0
EEF2	0.014	0	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.013	0.009	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	0.018	0	-9999	-10000	0	0
BAD/BCL-XL/YWHAZ	0	0	-9999	-10000	0	0
CDKN1B	0.03	0	-9999	-10000	0	0
CDKN1A	0.029	0.012	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
PRKDC	0.01	0	-9999	-10000	0	0
FOXO3	0.03	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
BAD	0.01	0	-9999	-10000	0	0
AKT3	0.011	0.026	-9999	-0.31	3	3
mol:GTP	0	0	-9999	-10000	0	0
FOXO4	0.03	0	-9999	-10000	0	0
AKT1/ASK1	0	0	-9999	-10000	0	0
BAD/YWHAZ	0	0	-9999	-10000	0	0
RICTOR	0.01	0	-9999	-10000	0	0
RAF1	0.01	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
TSC1	0.03	0	-9999	-10000	0	0
YWHAZ	0.01	0	-9999	-10000	0	0
AKT1/RAF1	0.029	0	-9999	-10000	0	0
EP300	0.01	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
TSC2	0.03	0	-9999	-10000	0	0
YWHAQ	0.01	0	-9999	-10000	0	0
TBC1D4	0.019	0	-9999	-10000	0	0
MAP3K5	0.01	0	-9999	-10000	0	0
MAPKAP1	0.01	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.034	0.013	-9999	-10000	0	0
YWHAH	0.01	0	-9999	-10000	0	0
AKT1S1	0.03	0	-9999	-10000	0	0
CASP9	0.03	0	-9999	-10000	0	0
YWHAB	0.01	0	-9999	-10000	0	0
p27Kip1/KPNA1	0.034	0	-9999	-10000	0	0
GBL	0	0	-9999	-10000	0	0
PDK1/Src/Hsp90	0	0	-9999	-10000	0	0
YWHAE	0.01	0	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
AKT2/p21CIP1	0	0.01	-9999	-10000	0	0
KIAA1303	0	0	-9999	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.014	0.003	-9999	-10000	0	0
CHUK	0.03	0	-9999	-10000	0	0
BAD/BCL-XL	0.039	0	-9999	-10000	0	0
mTORC2	0	0	-9999	-10000	0	0
AKT2	0.014	0	-9999	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.046	0.012	-9999	-10000	0	0
PDPK1	0.01	0	-9999	-10000	0	0
MDM2	0.029	0.017	-9999	-10000	0	0
MAPKKK cascade	-0.029	0	-9999	-10000	0	0
MDM2/Cbp/p300	0.038	0.016	-9999	-10000	0	0
TSC1/TSC2	0.035	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.001	0.013	-9999	-10000	0	0
glucose import	0.021	0.032	-9999	-0.26	6	6
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.025	0.003	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	0.021	0.032	-9999	-0.26	6	6
GSK3A	0.03	0	-9999	-10000	0	0
FOXO1	0.03	0	-9999	-10000	0	0
GSK3B	0.03	0	-9999	-10000	0	0
SFN	0	0.072	-9999	-0.51	9	9
G1/S transition of mitotic cell cycle	0.035	0	-9999	-10000	0	0
p27Kip1/14-3-3 family	0.036	0.017	-9999	-10000	0	0
PRKACA	0.01	0	-9999	-10000	0	0
KPNA1	0.01	0	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
YWHAG	0.01	0	-9999	-10000	0	0
RHEB	0.009	0.024	-9999	-0.51	1	1
CREBBP	0.01	0	-9999	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.01	0	-9999	-10000	0	0
Rac1/GDP	0	0.003	-9999	-10000	0	0
DOCK1	0.01	0	-9999	-10000	0	0
ITGA4	0.008	0.033	-9999	-0.5	2	2
RAC1	0.01	0	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.002	0.028	-9999	-0.35	3	3
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.001	0.019	-9999	-0.29	2	2
alpha4/beta7 Integrin/Paxillin	-0.002	0.021	-9999	-0.26	3	3
lamellipodium assembly	-0.001	0.019	-9999	-0.34	1	1
PIK3CA	0.01	0	-9999	-10000	0	0
PI3K	-0.001	0.016	-9999	-0.35	1	1
ARF6	0.01	0	-9999	-10000	0	0
TLN1	0.009	0.024	-9999	-0.5	1	1
PXN	0.018	0	-9999	-10000	0	0
PIK3R1	0.009	0.024	-9999	-0.5	1	1
ARF6/GTP	-0.001	0.014	-9999	-10000	0	0
cell adhesion	-0.002	0.019	-9999	-10000	0	0
CRKL/CBL	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	-0.001	0.017	-9999	-0.26	2	2
ITGB1	0.01	0	-9999	-10000	0	0
ITGB7	0.009	0.024	-9999	-0.5	1	1
ARF6/GDP	0	0.003	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.003	0.027	-9999	-10000	0	0
p130Cas/Crk/Dock1	-0.001	0.013	-9999	-0.29	1	1
VCAM1	0.005	0.047	-9999	-0.5	4	4
alpha4/beta1 Integrin/Paxillin/Talin	-0.002	0.019	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.001	0.015	-9999	-10000	0	0
BCAR1	0.009	0.024	-9999	-0.5	1	1
mol:GDP	0.001	0.015	-9999	-10000	0	0
CBL	0.01	0	-9999	-10000	0	0
PRKACA	0.01	0	-9999	-10000	0	0
GIT1	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.002	0.019	-9999	-10000	0	0
Rac1/GTP	-0.001	0.021	-9999	-0.38	1	1

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	-0.001	0.016	-9999	-0.35	1	1
FBXW11	0.01	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.021	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.036	0.02	-9999	-10000	0	0
NFKBIA	0.021	0.023	-9999	-0.2	5	5
MAPK14	0.01	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.021	0	-9999	-10000	0	0
ARRB2	0.014	0	-9999	-10000	0	0
REL	0.01	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.02	0.014	-9999	-0.29	1	1
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.021	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
NF kappa B1 p50 dimer	0.016	0	-9999	-10000	0	0
PIK3R1	0.009	0.024	-9999	-0.5	1	1
NFKB1	0.018	0	-9999	-10000	0	0
RELA	0.01	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.026	0.023	-9999	-0.2	2	2
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.038	0.02	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
PI3K	-0.001	0.016	-9999	-0.35	1	1
NF kappa B1 p50/RelA	0.026	0.023	-9999	-0.2	2	2
IKBKB	0.01	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.01	0	-9999	-10000	0	0
SYK	0.007	0.041	-9999	-0.5	3	3
I kappa B alpha/PIK3R1	0.024	0.025	-9999	-0.23	1	1
cell death	-0.002	0.015	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	0.021	0	-9999	-10000	0	0
LCK	0.007	0.041	-9999	-0.5	3	3
BCL3	0.009	0.024	-9999	-0.5	1	1

×

Sumoylation by RanBP2 regulates transcriptional repression

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.01	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.001	0.013	-9999	-10000	0	0
MDM2/SUMO1	0.022	0.017	-9999	-0.24	2	2
HDAC4	0.009	0.024	-9999	-0.51	1	1
Ran/GTP/Exportin 1/HDAC1	0	0.009	-9999	-10000	0	0
SUMO1	0.01	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.023	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.009	0.024	-9999	-0.51	1	1
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.01	0	-9999	-10000	0	0
SUMO1/HDAC4	0.023	0.012	-9999	-0.24	1	1
SUMO1/HDAC1	0.023	0	-9999	-10000	0	0
RANGAP1	0.01	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	-0.001	0.017	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.017	0	-9999	-10000	0	0
Ran/GTP	-0.001	0.011	-9999	-0.24	1	1
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.008	0.034	-9999	-0.51	2	2
UBE2I	0.01	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0.01	-9999	-0.23	1	1
NPC	0	0	-9999	-10000	0	0
PIAS2	0.01	0	-9999	-10000	0	0
PIAS1	0.01	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

E-cadherin signaling in keratinocytes

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0.038	0.017	-9999	-10000	0	0
adherens junction organization	0.032	0.025	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
Rac1/GDP	0.036	0.043	-9999	-10000	0	0
FMN1	0.025	0.049	-9999	-10000	0	0
mol:IP3	-0.001	0.013	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.029	0.019	-9999	-0.23	2	2
CTNNB1	0.01	0.001	-9999	-10000	0	0
AKT1	0.037	0.017	-9999	-10000	0	0
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.029	0.029	-9999	-0.36	2	2
CTNND1	0.011	0.001	-9999	-10000	0	0
mol:PI-4-5-P2	0.034	0.017	-9999	-10000	0	0
VASP	0.034	0.018	-9999	-10000	0	0
ZYX	0.033	0.021	-9999	-10000	0	0
JUB	0.033	0.024	-9999	-10000	0	0
EGFR(dimer)	0.025	0.048	-9999	-0.32	1	1
E-cadherin/beta catenin-gamma catenin	-0.002	0.023	-9999	-0.29	3	3
mol:PI-3-4-5-P3	-0.001	0.014	-9999	-10000	0	0
PIK3CA	0.011	0.001	-9999	-10000	0	0
PI3K	-0.001	0.014	-9999	-10000	0	0
FYN	0.02	0.064	-9999	-10000	0	0
mol:Ca2+	-0.001	0.012	-9999	-10000	0	0
JUP	0.008	0.024	-9999	-0.51	1	1
PIK3R1	0.009	0.024	-9999	-0.5	1	1
mol:DAG	-0.001	0.013	-9999	-10000	0	0
CDH1	0.007	0.033	-9999	-0.5	2	2
RhoA/GDP	0.036	0.043	-9999	-10000	0	0
establishment of polarity of embryonic epithelium	0.034	0.017	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
RAC1	0.01	0	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
EGFR	-0.006	0.088	-9999	-0.51	14	14
CASR	0.009	0.078	-9999	-10000	0	0
RhoA/GTP	-0.001	0.011	-9999	-10000	0	0
AKT2	0.037	0.017	-9999	-10000	0	0
actin cable formation	0.03	0.048	-9999	-10000	0	0
apoptosis	0.001	0.014	-9999	-10000	0	0
CTNNA1	0.011	0.001	-9999	-10000	0	0
mol:GDP	0.031	0.046	-9999	-0.29	1	1
PIP5K1A	0.034	0.018	-9999	-10000	0	0
PLCG1	-0.001	0.013	-9999	-10000	0	0
Rac1/GTP	-0.007	0.038	-9999	-0.3	1	1
homophilic cell adhesion	0.001	0.001	-9999	-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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0	0	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.016	0	-9999	-10000	0	0
AP2	0	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0	-9999	-10000	0	0
CLTB	0.01	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.02	0	-9999	-10000	0	0
CD4	-0.001	0.074	-9999	-0.5	10	10
CLTA	0.01	0	-9999	-10000	0	0
mol:GTP	0.001	0	-9999	-10000	0	0
ARFGAP1	0.009	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
ARF1/GTP	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.022	0	-9999	-10000	0	0
mol:Choline	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.01	0	-9999	-10000	0	0
DDEF1	0	0	-9999	-10000	0	0
ARF1/GDP	0	0	-9999	-10000	0	0
AP2M1	0.01	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0	0	-9999	-10000	0	0
Rac/GTP	0	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0	0	-9999	-10000	0	0
ARFIP2	0	0	-9999	-10000	0	0
COPA	0.01	0	-9999	-10000	0	0
RAC1	0.01	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.02	0	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0	-9999	-10000	0	0
GGA3	0.01	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0	0	-9999	-10000	0	0
AP2A1	0.01	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.022	0	-9999	-10000	0	0
ARF1/GDP/Membrin	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0	0	-9999	-10000	0	0
CYTH2	0.01	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0	0	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0	0	-9999	-10000	0	0
mol:Brefeldin A	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.024	0.032	-9999	-10000	0	0
PLD2	0	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.009	0	-9999	-10000	0	0
PIP5K1A	0	0	-9999	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0	0	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	0.009	0	-9999	-10000	0	0
GOSR2	0	0	-9999	-10000	0	0
USO1	0	0	-9999	-10000	0	0
GBF1	0	0	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	-0.006	0.042	-9999	-0.29	10	10

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
IKK alpha homodimer	0	-9999	-9999
FBXW11	0.01	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	0	-9999	-9999
beta TrCP1/SCF ubiquitin ligase complex	0.01	-9999	-9999
CHUK	0.01	-9999	-9999
NF kappa B2 p100/RelB	0	-9999	-9999
NFKB1	0.01	-9999	-9999
MAP3K14	0.01	-9999	-9999
NF kappa B1 p50/RelB	0	-9999	-9999
RELB	0.01	-9999	-9999
NFKB2	0.01	-9999	-9999
NF kappa B2 p52/RelB	0	-9999	-9999
regulation of B cell activation	0	-9999	-9999

pid_entity	TCGA.MP.A4TK	TCGA.MP.A4TI	TCGA.MP.A4TC	TCGA.MP.A4TA
109_MAP3K5	0.043	0.043	0.043	0.043
47_PPARGC1A	0.0098	0.0098	-0.5	0.0098
105_BMP4	0.0098	0.0098	0.0098	0.0098
105_BMP6	0.0098	0.0098	-0.5	0.0098
105_BMP7	0.0098	0.0098	0.0098	0.0098
105_BMP2	0.0098	0.0098	0.0098	-0.5
131_RELN/VLDLR	0	0	0	0
30_TGFB1/TGF beta receptor Type II	0.0093	0.0093	0.0093	0.014
84_STAT5B	0.035	0.037	0.035	-0.027
84_STAT5A	0.035	0.037	0.035	-0.027