PARADIGM pathway analysis of mRNASeq expression data - Breast Invasive Carcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
Class IB PI3K non-lipid kinase events	307
Signaling events mediated by Stem cell factor receptor (c-Kit)	292
EGFR-dependent Endothelin signaling events	250
Signaling mediated by p38-alpha and p38-beta	225
HIF-1-alpha transcription factor network	214
Reelin signaling pathway	205
FOXA2 and FOXA3 transcription factor networks	169
p75(NTR)-mediated signaling	168
Angiopoietin receptor Tie2-mediated signaling	165
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	161

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
Class IB PI3K non-lipid kinase events	0.2814	307	921	3	-0.22	-1000	1000	-1000	-0.023	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.2676	292	22821	78	-0.62	0.19	1000	-1000	-0.064	-1000
EGFR-dependent Endothelin signaling events	0.2291	250	5258	21	-0.34	0	1000	-1000	-0.067	-1000
Signaling mediated by p38-alpha and p38-beta	0.2062	225	9907	44	-0.4	0	1000	-1000	-0.047	-1000
HIF-1-alpha transcription factor network	0.1962	214	16273	76	-0.74	0.019	1000	-1000	-0.067	-1000
Reelin signaling pathway	0.1879	205	11522	56	-0.47	0	1000	-1000	-0.098	-1000
FOXA2 and FOXA3 transcription factor networks	0.1549	169	7786	46	-1.2	0.023	1000	-1000	-0.034	-1000
p75(NTR)-mediated signaling	0.1540	168	21003	125	-0.37	0	1000	-1000	-0.098	-1000
Angiopoietin receptor Tie2-mediated signaling	0.1512	165	14528	88	-0.38	0.04	1000	-1000	-0.099	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.1476	161	11012	68	-0.51	0.16	1000	-1000	-0.099	-1000
Glucocorticoid receptor regulatory network	0.1430	156	17830	114	-0.92	0.34	1000	-1000	-0.074	-1000
IL4-mediated signaling events	0.1320	144	13191	91	-0.99	0.52	1000	-1000	-0.13	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.1292	141	7649	54	-0.47	0.022	1000	-1000	-0.092	-1000
Arf6 signaling events	0.1292	141	8787	62	-0.34	0.017	1000	-1000	-0.058	-1000
Wnt signaling	0.1265	138	967	7	-0.16	-0.007	1000	-1000	-0.048	-1000
FOXM1 transcription factor network	0.1228	134	6846	51	-0.44	0.014	1000	-1000	-0.14	-1000
Aurora B signaling	0.1228	134	8982	67	-0.32	0.009	1000	-1000	-0.06	-1000
Endothelins	0.1219	133	12850	96	-0.37	0.041	1000	-1000	-0.068	-1000
Ephrin B reverse signaling	0.1137	124	5957	48	-0.31	0.17	1000	-1000	-0.071	-1000
ErbB2/ErbB3 signaling events	0.1118	122	7950	65	-0.38	0.018	1000	-1000	-0.063	-1000
EPHB forward signaling	0.1091	119	10197	85	-0.31	0.17	1000	-1000	-0.085	-1000
IGF1 pathway	0.1072	117	6690	57	-0.18	0.08	1000	-1000	-0.089	-1000
Signaling events regulated by Ret tyrosine kinase	0.1027	112	9184	82	-0.17	0	1000	-1000	-0.076	-1000
BMP receptor signaling	0.0972	106	8599	81	-0.54	0.026	1000	-1000	-0.084	-1000
Calcium signaling in the CD4+ TCR pathway	0.0972	106	3315	31	-0.32	0.012	1000	-1000	-0.092	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0944	103	8816	85	-0.24	0.011	1000	-1000	-0.063	-1000
Nongenotropic Androgen signaling	0.0944	103	5356	52	-0.23	0.11	1000	-1000	-0.062	-1000
ErbB4 signaling events	0.0935	102	7099	69	-0.41	0.057	1000	-1000	-0.086	-1000
Syndecan-1-mediated signaling events	0.0898	98	3339	34	-0.22	0	1000	-1000	-0.062	-1000
Noncanonical Wnt signaling pathway	0.0898	98	2567	26	-0.16	0	1000	-1000	-0.074	-1000
Plasma membrane estrogen receptor signaling	0.0898	98	8491	86	-0.19	0.095	1000	-1000	-0.077	-1000
Glypican 1 network	0.0889	97	4660	48	-0.32	0.03	1000	-1000	-0.053	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0871	95	11458	120	-0.58	0.24	1000	-1000	-0.074	-1000
Signaling events mediated by PTP1B	0.0843	92	7007	76	-0.62	0.071	1000	-1000	-0.072	-1000
Aurora C signaling	0.0843	92	644	7	-0.17	0	1000	-1000	-0.04	-1000
Integrins in angiogenesis	0.0816	89	7534	84	-0.34	0	1000	-1000	-0.084	-1000
IL6-mediated signaling events	0.0816	89	6695	75	-0.28	0.051	1000	-1000	-0.073	-1000
IL23-mediated signaling events	0.0779	85	5149	60	-0.46	0.018	1000	-1000	-0.13	-1000
Visual signal transduction: Rods	0.0742	81	4250	52	-0.48	0	1000	-1000	-0.082	-1000
amb2 Integrin signaling	0.0733	80	6622	82	-0.48	0	1000	-1000	-0.072	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0724	79	2717	34	-0.096	0	1000	-1000	-0.049	-1000
Ephrin A reverse signaling	0.0687	75	527	7	-0.076	0	1000	-1000	-0.028	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0678	74	3867	52	-0.19	0.029	1000	-1000	-0.058	-1000
S1P1 pathway	0.0669	73	2631	36	-0.33	0.008	1000	-1000	-0.064	-1000
Signaling events mediated by PRL	0.0669	73	2491	34	-0.17	0.02	1000	-1000	-0.053	-1000
Syndecan-3-mediated signaling events	0.0651	71	2514	35	-0.35	0	1000	-1000	-0.063	-1000
LPA receptor mediated events	0.0651	71	7302	102	-0.3	0.028	1000	-1000	-0.081	-1000
Signaling events mediated by the Hedgehog family	0.0632	69	3606	52	-0.22	0.031	1000	-1000	-0.065	-1000
Fc-epsilon receptor I signaling in mast cells	0.0632	69	6778	97	-0.24	0.028	1000	-1000	-0.079	-1000
PDGFR-alpha signaling pathway	0.0623	68	3019	44	-0.36	0.019	1000	-1000	-0.065	-1000
Ras signaling in the CD4+ TCR pathway	0.0550	60	1024	17	-0.12	-0.001	1000	-1000	-0.059	-1000
PLK1 signaling events	0.0522	57	4917	85	-0.22	0.029	1000	-1000	-0.053	-1000
Nectin adhesion pathway	0.0522	57	3598	63	-0.088	0.001	1000	-1000	-0.061	-1000
Presenilin action in Notch and Wnt signaling	0.0504	55	3414	61	-0.42	0.014	1000	-1000	-0.069	-1000
Rapid glucocorticoid signaling	0.0504	55	1103	20	-0.19	0.027	1000	-1000	-0.036	-1000
Visual signal transduction: Cones	0.0495	54	2067	38	-0.17	0.011	1000	-1000	-0.064	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0495	54	1809	33	-0.54	0	1000	-1000	-0.054	-1000
FAS signaling pathway (CD95)	0.0477	52	2473	47	-0.47	0.013	1000	-1000	-0.045	-1000
Glypican 2 network	0.0477	52	211	4	-0.038	-0.031	1000	-1000	-0.034	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0477	52	3877	74	-0.3	0.072	1000	-1000	-0.091	-1000
Signaling events mediated by HDAC Class III	0.0467	51	2076	40	-0.56	0.022	1000	-1000	-0.038	-1000
TCGA08_rtk_signaling	0.0458	50	1316	26	-0.3	0.026	1000	-1000	-0.028	-1000
E-cadherin signaling in keratinocytes	0.0449	49	2112	43	-0.3	0.04	1000	-1000	-0.074	-1000
LPA4-mediated signaling events	0.0440	48	584	12	-0.16	0.02	1000	-1000	-0.018	-1000
Effects of Botulinum toxin	0.0431	47	1236	26	-0.1	0.001	1000	-1000	-0.058	-1000
IL27-mediated signaling events	0.0431	47	2414	51	-0.29	0.035	1000	-1000	-0.068	-1000
TCR signaling in naïve CD8+ T cells	0.0412	45	4210	93	-0.16	0.078	1000	-1000	-0.065	-1000
Canonical Wnt signaling pathway	0.0412	45	2333	51	-0.42	0.14	1000	-1000	-0.048	-1000
Syndecan-4-mediated signaling events	0.0412	45	3058	67	-0.32	0.005	1000	-1000	-0.08	-1000
IL12-mediated signaling events	0.0394	43	3786	87	-0.35	0.046	1000	-1000	-0.1	-1000
Coregulation of Androgen receptor activity	0.0367	40	3091	76	-0.18	0.034	1000	-1000	-0.051	-1000
Insulin Pathway	0.0367	40	3015	74	-0.21	0.033	1000	-1000	-0.084	-1000
Regulation of Androgen receptor activity	0.0367	40	2850	70	-0.25	0.021	1000	-1000	-0.065	-1000
Regulation of Telomerase	0.0357	39	4004	102	-0.34	0.025	1000	-1000	-0.076	-1000
Osteopontin-mediated events	0.0330	36	1384	38	-0.24	0.022	1000	-1000	-0.092	-1000
Regulation of p38-alpha and p38-beta	0.0312	34	1872	54	-0.35	0.029	1000	-1000	-0.067	-1000
TCGA08_retinoblastoma	0.0312	34	277	8	-0.054	0.01	1000	-1000	-0.024	-1000
Syndecan-2-mediated signaling events	0.0302	33	2324	69	-0.2	0.034	1000	-1000	-0.055	-1000
IL2 signaling events mediated by STAT5	0.0302	33	726	22	-0.11	0.063	1000	-1000	-0.045	-1000
BCR signaling pathway	0.0293	32	3207	99	-0.13	0.042	1000	-1000	-0.082	-1000
Regulation of nuclear SMAD2/3 signaling	0.0284	31	4273	136	-0.3	0.052	1000	-1000	-0.073	-1000
Thromboxane A2 receptor signaling	0.0275	30	3245	105	-0.3	0.066	1000	-1000	-0.068	-1000
Aurora A signaling	0.0266	29	1752	60	-0.21	0.006	1000	-1000	-0.056	-1000
Arf6 trafficking events	0.0257	28	2008	71	-0.44	0.032	1000	-1000	-0.071	-1000
Hedgehog signaling events mediated by Gli proteins	0.0174	19	1267	65	-0.066	0.044	1000	-1000	-0.078	-1000
Class I PI3K signaling events mediated by Akt	0.0174	19	1330	68	-0.25	0.054	1000	-1000	-0.057	-1000
Ceramide signaling pathway	0.0174	19	1498	76	-0.18	0.049	1000	-1000	-0.054	-1000
TRAIL signaling pathway	0.0174	19	947	48	-0.076	0.045	1000	-1000	-0.063	-1000
Retinoic acid receptors-mediated signaling	0.0174	19	1157	58	-0.1	0.037	1000	-1000	-0.067	-1000
Caspase cascade in apoptosis	0.0165	18	1353	74	-0.048	0.045	1000	-1000	-0.057	-1000
BARD1 signaling events	0.0165	18	1053	57	-0.11	0.024	1000	-1000	-0.065	-1000
JNK signaling in the CD4+ TCR pathway	0.0165	18	313	17	-0.02	0.043	1000	-1000	-0.059	-1000
Cellular roles of Anthrax toxin	0.0165	18	703	39	-0.14	0.02	1000	-1000	-0.028	-1000
Signaling mediated by p38-gamma and p38-delta	0.0165	18	274	15	-0.019	0.022	1000	-1000	-0.044	-1000
E-cadherin signaling events	0.0165	18	93	5	-0.022	0	1000	-1000	-0.04	-1000
IL2 signaling events mediated by PI3K	0.0156	17	1005	58	-0.043	0.06	1000	-1000	-0.072	-1000
PLK2 and PLK4 events	0.0137	15	47	3	-0.012	0.013	1000	-1000	-0.025	-1000
IL1-mediated signaling events	0.0137	15	952	62	-0.037	0.031	1000	-1000	-0.093	-1000
S1P5 pathway	0.0128	14	250	17	-0.045	0.024	1000	-1000	-0.057	-1000
S1P4 pathway	0.0128	14	364	25	-0.045	0.008	1000	-1000	-0.054	-1000
S1P3 pathway	0.0119	13	577	42	-0.033	0.021	1000	-1000	-0.059	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0110	12	343	28	-0.045	0.02	1000	-1000	-0.047	-1000
mTOR signaling pathway	0.0101	11	620	53	-0.021	0.025	1000	-1000	-0.059	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0101	11	954	83	-0.037	0.054	1000	-1000	-0.071	-1000
E-cadherin signaling in the nascent adherens junction	0.0101	11	895	76	-0.022	0.05	1000	-1000	-0.08	-1000
p38 MAPK signaling pathway	0.0101	11	527	44	-0.068	0.025	1000	-1000	-0.061	-1000
Signaling events mediated by HDAC Class II	0.0082	9	736	75	-0.15	0	1000	-1000	-0.06	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0082	9	364	37	-0.048	0.034	1000	-1000	-0.073	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0082	9	1234	125	-0.17	0.082	1000	-1000	-0.09	-1000
IFN-gamma pathway	0.0073	8	591	68	-0.068	0.075	1000	-1000	-0.082	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0073	8	371	45	-0.025	0.073	1000	-1000	-0.079	-1000
VEGFR1 specific signals	0.0073	8	479	56	-0.17	0.065	1000	-1000	-0.071	-1000
EPO signaling pathway	0.0064	7	430	55	-0.036	0.058	1000	-1000	-0.077	-1000
HIF-2-alpha transcription factor network	0.0064	7	337	43	-0.17	0.18	1000	-1000	-0.066	-1000
Class I PI3K signaling events	0.0064	7	522	73	-0.044	0.059	1000	-1000	-0.068	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0055	6	150	23	-0.029	0.042	1000	-1000	-0.062	-1000
PDGFR-beta signaling pathway	0.0055	6	625	97	-0.026	0.05	1000	-1000	-0.079	-1000
FoxO family signaling	0.0046	5	377	64	-0.038	0.09	1000	-1000	-0.074	-1000
Atypical NF-kappaB pathway	0.0046	5	176	31	-0.02	0.03	1000	-1000	-0.063	-1000
Circadian rhythm pathway	0.0037	4	89	22	-0.014	0.042	1000	-1000	-0.066	-1000
ceramide signaling pathway	0.0037	4	239	49	-0.027	0.054	1000	-1000	-0.05	-1000
Signaling events mediated by HDAC Class I	0.0037	4	509	104	-0.094	0.046	1000	-1000	-0.066	-1000
Canonical NF-kappaB pathway	0.0027	3	130	39	-0.021	0.077	1000	-1000	-0.078	-1000
a4b1 and a4b7 Integrin signaling	0.0027	3	18	5	-0.01	-0.002	1000	-1000	-0.039	-1000
Arf6 downstream pathway	0.0027	3	142	43	-0.023	0.023	1000	-1000	-0.043	-1000
Insulin-mediated glucose transport	0.0027	3	104	32	-0.13	0.032	1000	-1000	-0.057	-1000
Paxillin-dependent events mediated by a4b1	0.0027	3	110	36	-0.011	0.022	1000	-1000	-0.073	-1000
TCGA08_p53	0.0000	0	0	7	-0.026	0.017	1000	-1000	-0.022	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	8	27	-0.001	0.029	1000	-1000	-0.055	-1000
Arf1 pathway	0.0000	0	26	54	-0.001	0.025	1000	-1000	-0.042	-1000
Alternative NF-kappaB pathway	0.0000	0	11	13	-0.003	0	1000	-1000	-0.051	-1000
Total	NA	8172	481110	7203	-31	-990	131000	-131000	-8.6	-131000

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	0.22	0.35	0.79	307	-10000	0	307
PI3K Class IB/PDE3B	-0.22	0.35	-10000	0	-0.79	307	307
PDE3B	-0.22	0.36	-10000	0	-0.79	307	307

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	-0.16	0.22	-10000	0	-0.39	501	501
CRKL	-0.17	0.23	-10000	0	-0.41	502	502
HRAS	-0.16	0.17	-10000	0	-0.5	47	47
mol:PIP3	-0.17	0.21	-10000	0	-0.4	503	503
SPRED1	0	0	-10000	0	-10000	0	0
SPRED2	0	0	-10000	0	-10000	0	0
GAB1	-0.18	0.24	-10000	0	-0.44	502	502
FOXO3	-0.15	0.21	-10000	0	-0.37	500	500
AKT1	-0.17	0.22	-10000	0	-0.41	501	501
BAD	-0.15	0.21	-10000	0	-0.37	500	500
megakaryocyte differentiation	-0.18	0.24	-10000	0	-0.43	503	503
GSK3B	-0.15	0.21	-10000	0	-0.37	500	500
RAF1	-0.093	0.17	-10000	0	-0.44	28	28
SHC1	0	0	-10000	0	-10000	0	0
STAT3	-0.18	0.24	-10000	0	-0.44	502	502
STAT1	-0.46	0.56	-10000	0	-1	512	512
HRAS/SPRED1	-0.13	0.14	-10000	0	-0.4	43	43
cell proliferation	-0.18	0.24	-10000	0	-0.44	503	503
PIK3CA	0	0.009	-10000	0	-0.29	1	1
TEC	-0.002	0.041	-10000	0	-0.79	3	3
RPS6KB1	-0.18	0.24	-10000	0	-0.44	504	504
HRAS/SPRED2	-0.13	0.14	-10000	0	-0.39	44	44
LYN/TEC/p62DOK	-0.19	0.2	-10000	0	-0.4	502	502
MAPK3	-0.055	0.13	-10000	0	-0.32	22	22
STAP1	-0.2	0.24	-10000	0	-0.45	504	504
GRAP2	-0.015	0.1	-10000	0	-0.72	22	22
JAK2	-0.4	0.44	-10000	0	-0.87	512	512
STAT1 (dimer)	-0.44	0.54	-10000	0	-1	512	512
mol:Gleevec	0.006	0.009	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.19	0.2	-10000	0	-0.41	502	502
actin filament polymerization	-0.19	0.24	-10000	0	-0.44	502	502
LYN	0	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.27	0.33	-10000	0	-0.62	505	505
PIK3R1	-0.009	0.086	-10000	0	-0.79	13	13
CBL/CRKL/GRB2	-0.17	0.18	-10000	0	-0.36	500	500
PI3K	-0.19	0.21	-10000	0	-0.41	507	507
PTEN	-0.001	0.034	-10000	0	-0.79	2	2
SCF/KIT/EPO/EPOR	-0.57	0.7	-10000	0	-1.3	500	500
MAPK8	-0.19	0.24	-10000	0	-0.45	503	503
STAT3 (dimer)	-0.18	0.23	-10000	0	-0.43	502	502
positive regulation of transcription	-0.042	0.11	-10000	0	-0.25	22	22
mol:GDP	-0.17	0.18	-10000	0	-0.49	59	59
PIK3C2B	-0.18	0.24	-10000	0	-0.44	502	502
CBL/CRKL	-0.15	0.22	-10000	0	-0.38	500	500
FER	-0.19	0.24	-10000	0	-0.44	507	507
SH2B3	-0.18	0.24	-10000	0	-0.44	502	502
PDPK1	-0.15	0.2	-10000	0	-0.36	502	502
SNAI2	-0.19	0.25	-10000	0	-0.45	504	504
positive regulation of cell proliferation	-0.32	0.4	-10000	0	-0.75	512	512
KITLG	0.002	0.067	-10000	0	-0.49	16	16
cell motility	-0.32	0.4	-10000	0	-0.75	512	512
PTPN6	0.015	0.021	-10000	0	-0.29	2	2
EPOR	-0.097	0.16	-10000	0	-10000	0	0
STAT5A (dimer)	-0.26	0.34	-10000	0	-0.62	514	514
SOCS1	-0.005	0.043	-10000	0	-0.32	18	18
cell migration	0.19	0.24	0.44	510	-10000	0	510
SOS1	0	0	-10000	0	-10000	0	0
EPO	-0.044	0.11	-10000	0	-0.3	177	177
VAV1	-0.003	0.043	-10000	0	-0.59	5	5
GRB10	-0.18	0.24	-10000	0	-0.44	502	502
PTPN11	0.013	0.013	-10000	0	-10000	0	0
SCF/KIT	-0.22	0.23	-10000	0	-0.46	514	514
GO:0007205	0.009	0.013	-10000	0	-10000	0	0
MAP2K1	-0.064	0.14	-10000	0	-0.35	22	22
CBL	0	0	-10000	0	-10000	0	0
KIT	-0.62	0.73	-10000	0	-1.4	498	498
MAP2K2	-0.064	0.14	-10000	0	-0.35	22	22
SHC/Grb2/SOS1	-0.19	0.2	-10000	0	-0.4	500	500
STAT5A	-0.27	0.35	-10000	0	-0.64	514	514
GRB2	0	0.009	-10000	0	-0.29	1	1
response to radiation	-0.18	0.24	-10000	0	-0.44	504	504
SHC/GRAP2	-0.011	0.079	-10000	0	-0.6	19	19
PTPRO	-0.18	0.24	-10000	0	-0.44	503	503
SH2B2	-0.19	0.24	-10000	0	-0.44	502	502
DOK1	-0.001	0.018	-10000	0	-10000	0	0
MATK	-0.2	0.25	-10000	0	-0.45	510	510
CREBBP	0.019	0.018	-10000	0	-10000	0	0
BCL2	-0.13	0.3	-10000	0	-1.5	37	37

×

EGFR-dependent Endothelin signaling events

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
HRAS	-0.002	0.027	-9999	-0.29	9	9
EGFR	-0.3	0.38	-9999	-0.78	414	414
EGF/EGFR	-0.28	0.3	-9999	-0.54	565	565
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.25	0.27	-9999	-0.49	555	555
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.001	0.025	-9999	-0.54	2	2
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.16	0.31	-9999	-0.78	216	216
EGF/EGFR dimer/SHC	-0.29	0.31	-9999	-0.58	555	555
mol:GDP	-0.25	0.26	-9999	-0.49	555	555
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.06	0.21	-9999	-0.78	83	83
GRB2/SOS1	0	0.006	-9999	-10000	0	0
HRAS/GTP	-0.23	0.24	-9999	-0.45	555	555
SHC1	0	0	-9999	-10000	0	0
HRAS/GDP	-0.23	0.25	-9999	-0.46	555	555
FRAP1	-0.24	0.25	-9999	-0.47	555	555
EGF/EGFR dimer	-0.34	0.35	-9999	-0.66	555	555
SOS1	0	0	-9999	-10000	0	0
GRB2	0	0.009	-9999	-0.29	1	1
ETA receptor/Endothelin-1	-0.046	0.16	-9999	-0.6	83	83

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	-0.4	0.62	-9999	-1.3	370	370
MKNK1	0	0	-9999	-10000	0	0
MAPK14	-0.081	0.15	-9999	-0.4	13	13
ATF2/c-Jun	-0.052	0.15	-9999	-0.78	14	14
MAPK11	-0.084	0.16	-9999	-0.3	373	373
MITF	-0.093	0.2	-9999	-0.36	377	377
MAPKAPK5	-0.089	0.19	-9999	-0.35	373	373
KRT8	-0.095	0.2	-9999	-0.36	374	374
MAPKAPK3	0	0	-9999	-10000	0	0
MAPKAPK2	0	0.009	-9999	-10000	0	0
p38alpha-beta/CK2	-0.12	0.23	-9999	-0.44	373	373
CEBPB	-0.089	0.19	-9999	-0.35	373	373
SLC9A1	-0.089	0.19	-9999	-0.35	373	373
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.082	0.19	-9999	-0.34	374	374
p38alpha-beta/MNK1	-0.12	0.17	-9999	-0.56	16	16
JUN	-0.051	0.15	-9999	-0.77	14	14
PPARGC1A	-0.21	0.36	-9999	-0.58	452	452
USF1	-0.089	0.19	-9999	-0.35	373	373
RAB5/GDP/GDI1	-0.085	0.12	-9999	-0.38	16	16
NOS2	-0.092	0.21	-9999	-0.87	16	16
DDIT3	-0.089	0.19	-9999	-0.35	373	373
RAB5A	0	0	-9999	-10000	0	0
HSPB1	-0.075	0.17	-9999	-0.43	54	54
p38alpha-beta/HBP1	-0.12	0.17	-9999	-0.56	16	16
CREB1	-0.094	0.2	-9999	-0.37	373	373
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	-0.07	0.17	-9999	-0.5	15	15
RPS6KA4	-0.089	0.19	-9999	-0.35	373	373
PLA2G4A	-0.13	0.27	-9999	-0.72	142	142
GDI1	-0.089	0.19	-9999	-0.35	373	373
TP53	-0.12	0.23	-9999	-0.44	373	373
RPS6KA5	-0.095	0.2	-9999	-0.36	381	381
ESR1	-0.18	0.26	-9999	-0.42	508	508
HBP1	0	0	-9999	-10000	0	0
MEF2C	-0.09	0.19	-9999	-0.35	373	373
MEF2A	-0.09	0.19	-9999	-0.35	373	373
EIF4EBP1	-0.094	0.2	-9999	-0.37	373	373
KRT19	-0.1	0.21	-9999	-0.37	378	378
ELK4	-0.089	0.19	-9999	-0.35	373	373
ATF6	-0.089	0.19	-9999	-0.35	373	373
ATF1	-0.094	0.2	-9999	-0.37	373	373
p38alpha-beta/MAPKAPK2	-0.12	0.17	-9999	-0.55	17	17
p38alpha-beta/MAPKAPK3	-0.12	0.17	-9999	-0.52	19	19

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.4	0.46	-9999	-0.99	304	304
HDAC7	0	0.002	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.32	0.31	-9999	-0.77	236	236
SMAD4	-0.001	0.024	-9999	-0.79	1	1
ID2	-0.4	0.46	-9999	-0.99	303	303
AP1	-0.18	0.28	-9999	-0.61	326	326
ABCG2	-0.43	0.5	-9999	-1.1	315	315
HIF1A	-0.05	0.065	-9999	-10000	0	0
TFF3	-0.47	0.52	-9999	-1.1	375	375
GATA2	-0.013	0.13	-9999	-0.62	42	42
AKT1	-0.05	0.081	-9999	-10000	0	0
response to hypoxia	-0.072	0.087	-9999	-0.24	35	35
MCL1	-0.4	0.46	-9999	-0.99	303	303
NDRG1	-0.4	0.47	-9999	-1	289	289
SERPINE1	-0.4	0.46	-9999	-0.99	304	304
FECH	-0.4	0.46	-9999	-0.99	302	302
FURIN	-0.4	0.46	-9999	-0.99	303	303
NCOA2	-0.03	0.17	-9999	-0.79	53	53
EP300	-0.048	0.12	-9999	-0.35	55	55
HMOX1	-0.4	0.46	-9999	-0.99	300	300
BHLHE40	-0.4	0.46	-9999	-0.99	302	302
BHLHE41	-0.41	0.48	-9999	-1	304	304
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.049	0.055	-9999	-0.6	1	1
ENG	-0.025	0.079	-9999	-0.54	1	1
JUN	0.003	0.064	-9999	-0.79	7	7
RORA	-0.4	0.46	-9999	-0.99	303	303
ABCB1	-0.34	0.55	-9999	-1.4	214	214
TFRC	-0.4	0.46	-9999	-0.99	305	305
CXCR4	-0.4	0.46	-9999	-0.99	301	301
TF	-0.63	0.58	-9999	-1.1	562	562
CITED2	-0.4	0.46	-9999	-0.99	303	303
HIF1A/ARNT	-0.48	0.53	-9999	-1.1	308	308
LDHA	-0.048	0.047	-9999	-10000	0	0
ETS1	-0.4	0.47	-9999	-0.99	301	301
PGK1	-0.4	0.46	-9999	-0.98	305	305
NOS2	-0.4	0.47	-9999	-1	303	303
ITGB2	-0.4	0.46	-9999	-0.99	303	303
ALDOA	-0.4	0.46	-9999	-0.99	304	304
Cbp/p300/CITED2	-0.42	0.45	-9999	-1	282	282
FOS	-0.23	0.37	-9999	-0.79	325	325
HK2	-0.4	0.46	-9999	-0.99	300	300
SP1	0.012	0.023	-9999	-10000	0	0
GCK	-0.13	0.36	-9999	-1.6	56	56
HK1	-0.4	0.46	-9999	-0.99	303	303
NPM1	-0.4	0.46	-9999	-0.99	303	303
EGLN1	-0.4	0.46	-9999	-0.99	302	302
CREB1	0.019	0	-9999	-10000	0	0
PGM1	-0.4	0.46	-9999	-0.99	303	303
SMAD3	0	0	-9999	-10000	0	0
EDN1	-0.18	0.4	-9999	-1.2	120	120
IGFBP1	-0.49	0.53	-9999	-1.1	377	377
VEGFA	-0.24	0.32	-9999	-0.74	128	128
HIF1A/JAB1	-0.028	0.026	-9999	-10000	0	0
CP	-0.51	0.55	-9999	-1.1	412	412
CXCL12	-0.43	0.5	-9999	-1.1	315	315
COPS5	0.009	0.006	-9999	-10000	0	0
SMAD3/SMAD4	-0.001	0.018	-9999	-0.6	1	1
BNIP3	-0.4	0.46	-9999	-0.99	302	302
EGLN3	-0.41	0.47	-9999	-1	311	311
CA9	-0.44	0.49	-9999	-1	322	322
TERT	-0.42	0.48	-9999	-1	314	314
ENO1	-0.4	0.46	-9999	-0.99	303	303
PFKL	-0.4	0.46	-9999	-0.99	302	302
NCOA1	0	0.024	-9999	-0.79	1	1
ADM	-0.43	0.49	-9999	-1	325	325
ARNT	-0.049	0.065	-9999	-10000	0	0
HNF4A	-0.002	0.046	-9999	-0.29	22	22
ADFP	-0.41	0.46	-9999	-0.99	306	306
SLC2A1	-0.24	0.32	-9999	-0.74	142	142
LEP	-0.74	0.53	-9999	-1.1	652	652
HIF1A/ARNT/Cbp/p300	-0.32	0.34	-9999	-0.8	241	241
EPO	-0.23	0.28	-9999	-0.86	49	49
CREBBP	-0.048	0.12	-9999	-0.36	53	53
HIF1A/ARNT/Cbp/p300/HDAC7	-0.31	0.31	-9999	-0.78	221	221
PFKFB3	-0.4	0.47	-9999	-1	304	304
NT5E	-0.4	0.47	-9999	-1	303	303

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	-0.006	0.034	-9999	-10000	0	0
VLDLR	-0.024	0.14	-9999	-0.79	33	33
CRKL	0	0	-9999	-10000	0	0
LRPAP1	0	0	-9999	-10000	0	0
FYN	-0.001	0.034	-9999	-0.79	2	2
ITGA3	-0.004	0.05	-9999	-0.58	7	7
RELN/VLDLR/Fyn	-0.32	0.27	-9999	-0.54	660	660
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.005	0.044	-9999	-0.44	11	11
AKT1	-0.2	0.17	-9999	-0.46	76	76
MAP2K7	0	0	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0
DAB1	-0.017	0.069	-9999	-10000	0	0
RELN/LRP8/DAB1	-0.31	0.24	-9999	-0.5	652	652
LRPAP1/LRP8	-0.019	0.057	-9999	-10000	0	0
RELN/LRP8/DAB1/Fyn	-0.29	0.23	-9999	-0.47	652	652
DAB1/alpha3/beta1 Integrin	-0.27	0.22	-9999	-0.58	145	145
long-term memory	-0.35	0.29	-9999	-0.53	706	706
DAB1/LIS1	-0.28	0.23	-9999	-0.51	277	277
DAB1/CRLK/C3G	-0.27	0.22	-9999	-0.57	142	142
PIK3CA	0	0.009	-9999	-0.29	1	1
DAB1/NCK2	-0.28	0.23	-9999	-0.46	657	657
ARHGEF2	0	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.092	0.25	-9999	-0.74	135	135
CDK5R1	-0.008	0.049	-9999	-0.29	31	31
RELN	-0.47	0.39	-9999	-0.79	654	654
PIK3R1	-0.009	0.086	-9999	-0.79	13	13
RELN/LRP8/Fyn	-0.32	0.26	-9999	-0.54	651	651
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.34	0.29	-9999	-0.53	671	671
MAPK8	-0.006	0.067	-9999	-0.79	8	8
RELN/VLDLR/DAB1	-0.31	0.25	-9999	-0.5	660	660
ITGB1	0	0	-9999	-10000	0	0
MAP1B	-0.3	0.25	-9999	-0.49	666	666
RELN/LRP8	-0.32	0.26	-9999	-0.54	651	651
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.32	0.25	-9999	-0.49	689	689
PI3K	-0.007	0.066	-9999	-0.6	13	13
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.003	0.038	-9999	-0.6	4	4
RAP1A	-0.25	0.2	-9999	-0.53	142	142
PAFAH1B1	0	0	-9999	-10000	0	0
MAPK8IP1	-0.004	0.046	-9999	-0.48	8	8
CRLK/C3G	0	0	-9999	-10000	0	0
GRIN2B	-0.053	0.2	-9999	-0.78	75	75
NCK2	0	0	-9999	-10000	0	0
neuron differentiation	-0.12	0.13	-9999	-0.47	12	12
neuron adhesion	-0.23	0.19	-9999	-0.6	47	47
LRP8	-0.031	0.09	-9999	-10000	0	0
GSK3B	-0.17	0.17	-9999	-0.45	69	69
RELN/VLDLR/DAB1/Fyn	-0.29	0.24	-9999	-0.47	660	660
MAP3K11	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.21	0.18	-9999	-0.35	667	667
CDK5	-0.002	0.023	-9999	-0.29	7	7
MAPT	-0.047	0.24	-9999	-0.69	129	129
neuron migration	-0.23	0.23	-9999	-0.49	167	167
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.13	0.11	-9999	-0.48	12	12
RELN/VLDLR	-0.31	0.25	-9999	-0.5	660	660

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.24	0.28	-9999	-0.77	128	128
PCK1	-1	0.7	-9999	-1.6	676	676
HNF4A	-0.25	0.28	-9999	-0.85	86	86
KCNJ11	-0.28	0.31	-9999	-0.88	126	126
AKT1	-0.15	0.14	-9999	-0.39	42	42
response to starvation	-0.001	0.008	-9999	-10000	0	0
DLK1	-0.5	0.56	-9999	-1.2	365	365
NKX2-1	-0.055	0.15	-9999	-10000	0	0
ACADM	-0.25	0.28	-9999	-0.78	130	130
TAT	-1.2	0.68	-9999	-1.6	776	776
CEBPB	0.006	0.007	-9999	-10000	0	0
CEBPA	-0.001	0.072	-9999	-0.79	9	9
TTR	-0.46	0.28	-9999	-0.8	300	300
PKLR	-0.25	0.28	-9999	-0.77	134	134
APOA1	-0.3	0.3	-9999	-0.89	105	105
CPT1C	-0.24	0.28	-9999	-0.79	116	116
ALAS1	-0.14	0.15	-9999	-10000	0	0
TFRC	-0.45	0.26	-9999	-0.69	437	437
FOXF1	-0.003	0.054	-9999	-0.5	10	10
NF1	0.017	0.024	-9999	-0.78	1	1
HNF1A (dimer)	0.003	0.027	-9999	-0.3	8	8
CPT1A	-0.24	0.28	-9999	-0.77	127	127
HMGCS1	-0.24	0.28	-9999	-0.8	107	107
NR3C1	-0.11	0.13	-9999	-0.48	50	50
CPT1B	-0.24	0.28	-9999	-0.75	149	149
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.002	0.007	-9999	-10000	0	0
GCK	-0.28	0.35	-9999	-0.94	158	158
CREB1	-0.059	0.067	-9999	-10000	0	0
IGFBP1	-0.44	0.59	-9999	-1.5	244	244
PDX1	-0.13	0.15	-9999	-10000	0	0
UCP2	-0.24	0.28	-9999	-0.74	153	153
ALDOB	-0.27	0.3	-9999	-0.83	131	131
AFP	-0.68	0.6	-9999	-1.1	604	604
BDH1	-0.24	0.28	-9999	-0.76	142	142
HADH	-0.26	0.3	-9999	-0.8	143	143
F2	-0.3	0.3	-9999	-0.89	98	98
HNF1A	0.003	0.027	-9999	-0.3	8	8
G6PC	-0.2	0.12	-9999	-0.64	8	8
SLC2A2	-0.16	0.17	-9999	-10000	0	0
INS	0.023	0.066	-9999	-10000	0	0
FOXA1	-0.24	0.28	-9999	-0.57	318	318
FOXA3	-0.42	0.23	-9999	-0.53	784	784
FOXA2	-0.32	0.34	-9999	-0.84	206	206
ABCC8	-0.34	0.43	-9999	-1.1	201	201
ALB	-0.93	0.64	-9999	-1.4	706	706

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	-0.001	0.018	-9999	-0.6	1	1
Necdin/E2F1	-0.082	0.15	-9999	-0.68	43	43
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.14	0.21	-9999	-0.45	346	346
NGF (dimer)/p75(NTR)/BEX1	-0.26	0.31	-9999	-0.62	425	425
NT-4/5 (dimer)/p75(NTR)	-0.37	0.41	-9999	-0.75	542	542
IKBKB	-0.001	0.013	-9999	-0.29	2	2
AKT1	-0.15	0.22	-9999	-0.45	350	350
IKBKG	0	0	-9999	-10000	0	0
BDNF	-0.065	0.21	-9999	-0.67	106	106
MGDIs/NGR/p75(NTR)/LINGO1	-0.2	0.25	-9999	-0.56	336	336
FURIN	0	0.009	-9999	-0.29	1	1
proBDNF (dimer)/p75(NTR)/Sortilin	-0.2	0.28	-9999	-0.57	380	380
LINGO1	-0.07	0.12	-9999	-0.29	262	262
Sortilin/TRAF6/NRIF	-0.001	0.024	-9999	-0.78	1	1
proBDNF (dimer)	-0.065	0.21	-9999	-0.67	106	106
NTRK1	-0.011	0.07	-9999	-0.37	33	33
RTN4R	-0.012	0.058	-9999	-0.29	44	44
neuron apoptosis	-0.14	0.26	-9999	-0.48	380	380
IRAK1	-0.001	0.018	-9999	-10000	0	0
SHC1	-0.15	0.26	-9999	-0.53	344	344
ARHGDIA	0	0	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
Gamma Secretase	0	0.014	-9999	-0.44	1	1
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.15	0.23	-9999	-0.48	344	344
MAGEH1	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.17	0.26	-9999	-0.52	358	358
Mammalian IAPs/DIABLO	-0.005	0.044	-9999	-0.47	9	9
proNGF (dimer)	-0.014	0.098	-9999	-0.62	24	24
MAGED1	-0.001	0.018	-9999	-0.29	4	4
APP	0	0	-9999	-10000	0	0
NT-4/5 (dimer)	-0.27	0.37	-9999	-0.79	372	372
ZNF274	0	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	-0.14	0.21	-9999	-0.45	344	344
NGF	-0.014	0.098	-9999	-0.62	24	24
cell cycle arrest	-0.12	0.23	-9999	-0.44	344	344
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.1	0.16	-9999	-0.33	344	344
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.33	0.36	-9999	-0.66	542	542
NCSTN	0	0	-9999	-10000	0	0
mol:GTP	-0.18	0.26	-9999	-0.54	344	344
PSENEN	0	0.009	-9999	-0.29	1	1
mol:ceramide	-0.13	0.24	-9999	-0.48	344	344
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.082	0.12	-9999	-0.48	13	13
p75(NTR)/beta APP	-0.18	0.28	-9999	-0.6	336	336
BEX1	-0.15	0.27	-9999	-0.52	319	319
mol:GDP	-0.16	0.26	-9999	-0.54	344	344
NGF (dimer)	-0.082	0.18	-9999	-0.48	173	173
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.18	0.22	-9999	-0.5	336	336
PIK3R1	-0.009	0.086	-9999	-0.79	13	13
RAC1/GTP	-0.15	0.22	-9999	-0.46	344	344
MYD88	0	0	-9999	-10000	0	0
CHUK	0	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.18	0.26	-9999	-0.54	344	344
RHOB	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
MAGE-G1/E2F1	-0.06	0.087	-9999	-10000	0	0
NT3 (dimer)	-0.13	0.28	-9999	-0.75	182	182
TP53	-0.16	0.23	-9999	-0.45	380	380
PRDM4	-0.13	0.24	-9999	-0.48	344	344
BDNF (dimer)	-0.17	0.23	-9999	-0.57	226	226
PIK3CA	0	0.009	-9999	-0.29	1	1
SORT1	-0.001	0.024	-9999	-0.79	1	1
activation of caspase activity	-0.14	0.21	-9999	-0.44	346	346
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.15	0.23	-9999	-0.48	344	344
RHOC	0	0	-9999	-10000	0	0
XIAP	0	0	-9999	-10000	0	0
MAPK10	-0.15	0.27	-9999	-0.49	351	351
DIABLO	0	0	-9999	-10000	0	0
SMPD2	-0.13	0.24	-9999	-0.48	344	344
APH1B	-0.001	0.024	-9999	-0.79	1	1
APH1A	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.17	0.25	-9999	-0.53	344	344
PSEN1	0	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-9999	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.27	0.35	-9999	-0.68	434	434
MAPK8	-0.11	0.24	-9999	-0.43	336	336
MAPK9	-0.1	0.24	-9999	-0.43	336	336
APAF1	0	0	-9999	-10000	0	0
NTF3	-0.13	0.29	-9999	-0.75	182	182
NTF4	-0.27	0.37	-9999	-0.79	372	372
NDN	-0.031	0.15	-9999	-0.79	43	43
RAC1/GDP	0	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.14	0.2	-9999	-0.42	344	344
p75 CTF/Sortilin/TRAF6/NRIF	0	0.014	-9999	-0.47	1	1
RhoA-B-C/GTP	-0.17	0.25	-9999	-0.54	344	344
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.17	0.24	-9999	-0.48	380	380
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.18	0.26	-9999	-0.52	380	380
PRKACB	-0.016	0.077	-9999	-0.33	53	53
proBDNF (dimer)/p75 ECD	-0.049	0.16	-9999	-0.6	80	80
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.01	0.077	-9999	-0.51	21	21
BIRC2	0	0	-9999	-10000	0	0
neuron projection morphogenesis	-0.12	0.25	-9999	-0.46	344	344
BAD	-0.12	0.24	-9999	-0.44	339	339
RIPK2	-0.001	0.02	-9999	-0.29	5	5
NGFR	-0.24	0.36	-9999	-0.79	336	336
CYCS	-0.14	0.21	-9999	-0.45	344	344
ADAM17	0	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.15	0.23	-9999	-0.48	344	344
BCL2L11	-0.12	0.24	-9999	-0.44	339	339
BDNF (dimer)/p75(NTR)	-0.23	0.32	-9999	-0.65	380	380
PI3K	-0.16	0.23	-9999	-0.49	350	350
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.15	0.23	-9999	-0.48	344	344
NDNL2	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
PRKCI	0	0.009	-9999	-10000	0	0
NGF (dimer)/p75(NTR)	-0.2	0.29	-9999	-0.61	344	344
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.15	0.23	-9999	-0.48	344	344
TRAF6	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
PRKCZ	-0.001	0.024	-9999	-0.79	1	1
PLG	-0.002	0.025	-9999	-0.29	8	8
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.19	0.26	-9999	-0.52	388	388
SQSTM1	0	0.009	-9999	-0.29	1	1
NGFRAP1	-0.001	0.034	-9999	-0.79	2	2
CASP3	-0.1	0.22	-9999	-0.41	339	339
E2F1	-0.094	0.14	-9999	-0.29	348	348
CASP9	0	0	-9999	-10000	0	0
IKK complex	-0.065	0.11	-9999	-0.56	22	22
NGF (dimer)/TRKA	-0.018	0.088	-9999	-0.6	21	21
MMP7	-0.12	0.28	-9999	-0.71	191	191
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.14	0.21	-9999	-0.45	344	344
MMP3	-0.12	0.16	-9999	-0.79	17	17
APAF-1/Caspase 9	-0.11	0.16	-9999	-0.64	15	15

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.13	0.42	-10000	0	-0.9	246	246
NCK1/PAK1/Dok-R	-0.095	0.18	-10000	0	-0.42	246	246
NCK1/Dok-R	-0.26	0.48	-10000	0	-1.1	246	246
PIK3CA	0.003	0.011	-10000	0	-0.29	1	1
mol:beta2-estradiol	0.039	0.1	0.24	209	-10000	0	209
RELA	0	0	-10000	0	-10000	0	0
SHC1	0.008	0.006	-10000	0	-10000	0	0
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	0.04	0.11	0.26	144	-0.32	11	155
TNIP2	0	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.24	0.44	-10000	0	-1	246	246
FN1	-0.12	0.14	-10000	0	-0.29	432	432
PLD2	-0.21	0.53	-10000	0	-1.2	246	246
PTPN11	0	0	-10000	0	-10000	0	0
GRB14	-0.1	0.22	-10000	0	-0.47	230	230
ELK1	-0.17	0.47	-10000	0	-1	246	246
GRB7	-0.023	0.085	-10000	0	-0.31	79	79
PAK1	-0.007	0.044	-10000	0	-0.29	25	25
Tie2/Ang1/alpha5/beta1 Integrin	-0.22	0.5	-10000	0	-1.1	246	246
CDKN1A	-0.07	0.28	-10000	0	-0.6	198	198
ITGA5	0	0.009	-10000	0	-0.29	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.26	0.48	-10000	0	-1.1	246	246
CRK	0	0	-10000	0	-10000	0	0
mol:NO	-0.076	0.32	-10000	0	-0.66	246	246
PLG	-0.22	0.53	-10000	0	-1.2	246	246
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.19	0.38	-10000	0	-0.88	246	246
GRB2	0	0.009	-10000	0	-0.29	1	1
PIK3R1	-0.002	0.087	-10000	0	-0.79	13	13
ANGPT2	-0.11	0.27	-10000	0	-0.7	135	135
BMX	-0.38	0.6	-10000	0	-1.4	247	247
ANGPT1	-0.25	0.58	-10000	0	-1.4	217	217
tube development	-0.088	0.31	-10000	0	-0.64	246	246
ANGPT4	-0.24	0.37	-10000	0	-0.79	330	330
response to hypoxia	-0.011	0.031	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.3	0.55	-10000	0	-1.3	246	246
alpha5/beta1 Integrin	0	0.006	-10000	0	-10000	0	0
FGF2	-0.32	0.39	-10000	0	-0.79	444	444
STAT5A (dimer)	-0.11	0.36	-10000	0	-0.75	225	225
mol:L-citrulline	-0.076	0.32	-10000	0	-0.66	246	246
AGTR1	-0.2	0.34	-10000	0	-0.69	327	327
MAPK14	-0.2	0.51	-10000	0	-1.1	246	246
Tie2/SHP2	-0.1	0.29	-10000	0	-1.3	56	56
TEK	-0.11	0.34	-10000	0	-1.5	56	56
RPS6KB1	-0.13	0.4	-10000	0	-0.87	246	246
Angiotensin II/AT1	-0.15	0.26	-10000	0	-0.53	327	327
Tie2/Ang1/GRB2	-0.28	0.52	-10000	0	-1.2	246	246
MAPK3	-0.18	0.49	-10000	0	-1.1	246	246
MAPK1	-0.18	0.49	-10000	0	-1.1	246	246
Tie2/Ang1/GRB7	-0.27	0.53	-10000	0	-1.2	246	246
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	-0.21	0.54	-10000	0	-1.2	246	246
PI3K	-0.17	0.48	-10000	0	-1.1	246	246
FES	-0.2	0.51	-10000	0	-1.1	246	246
Crk/Dok-R	-0.26	0.48	-10000	0	-1.1	246	246
Tie2/Ang1/ABIN2	-0.28	0.52	-10000	0	-1.2	246	246
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.11	0.38	-10000	0	-0.8	246	246
STAT5A	-0.005	0.068	-10000	0	-0.79	8	8
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.13	0.4	-10000	0	-0.87	246	246
Tie2/Ang2	-0.14	0.42	-10000	0	-0.88	245	245
Tie2/Ang1	-0.24	0.59	-10000	0	-1.3	246	246
FOXO1	-0.11	0.38	-10000	0	-0.81	247	247
ELF1	0.013	0.023	-10000	0	-10000	0	0
ELF2	-0.21	0.53	-10000	0	-1.2	246	246
mol:Choline	-0.19	0.5	-10000	0	-1.1	246	246
cell migration	-0.044	0.11	-10000	0	-0.24	246	246
FYN	-0.11	0.35	-10000	0	-0.73	245	245
DOK2	-0.003	0.045	-10000	0	-0.51	7	7
negative regulation of cell cycle	-0.06	0.26	-10000	0	-0.54	205	205
ETS1	-0.03	0.11	-10000	0	-0.96	5	5
PXN	-0.088	0.34	-10000	0	-0.71	246	246
ITGB1	0	0	-10000	0	-10000	0	0
NOS3	-0.096	0.36	-10000	0	-0.75	246	246
RAC1	0	0	-10000	0	-10000	0	0
TNF	-0.042	0.14	-10000	0	-0.76	18	18
MAPKKK cascade	-0.19	0.5	-10000	0	-1.1	246	246
RASA1	0	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.23	0.55	-10000	0	-1.2	246	246
NCK1	0	0	-10000	0	-10000	0	0
vasculogenesis	-0.062	0.29	-10000	0	-0.58	246	246
mol:Phosphatidic acid	-0.19	0.5	-10000	0	-1.1	246	246
mol:Angiotensin II	0.001	0.001	-10000	0	-10000	0	0
mol:NADP	-0.076	0.32	-10000	0	-0.66	246	246
Rac1/GTP	-0.18	0.34	-10000	0	-0.81	246	246
MMP2	-0.21	0.54	-10000	0	-1.2	246	246

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	-0.077	0.16	-10000	0	-0.39	144	144
NFATC2	-0.056	0.28	-10000	0	-0.76	126	126
NFATC3	-0.051	0.12	-10000	0	-0.31	49	49
CD40LG	-0.36	0.57	-10000	0	-1.1	335	335
ITCH	0.015	0.096	-10000	0	-10000	0	0
CBLB	0.015	0.096	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.25	0.36	-10000	0	-1.1	118	118
JUNB	-0.001	0.013	-10000	0	-0.29	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.034	0.1	-10000	0	-0.33	111	111
T cell anergy	-0.026	0.16	-10000	0	-0.48	111	111
TLE4	-0.031	0.26	-10000	0	-0.74	98	98
Jun/NFAT1-c-4/p21SNFT	-0.3	0.44	-10000	0	-0.93	306	306
AP-1/NFAT1-c-4	-0.51	0.66	-10000	0	-1.4	343	343
IKZF1	-0.02	0.21	-10000	0	-0.59	109	109
T-helper 2 cell differentiation	-0.12	0.3	-10000	0	-0.84	118	118
AP-1/NFAT1	-0.23	0.32	-10000	0	-0.64	371	371
CALM1	-0.018	0.053	-10000	0	-10000	0	0
EGR2	-0.29	0.64	-10000	0	-1.6	179	179
EGR3	-0.37	0.72	-10000	0	-1.5	290	290
NFAT1/FOXP3	-0.12	0.22	-10000	0	-0.57	146	146
EGR1	-0.24	0.37	-10000	0	-0.79	345	345
JUN	-0.001	0.066	-10000	0	-0.8	7	7
EGR4	-0.014	0.077	-10000	0	-0.31	3	3
mol:Ca2+	-0.021	0.061	-10000	0	-10000	0	0
GBP3	-0.024	0.22	-10000	0	-0.65	99	99
FOSL1	-0.009	0.06	-10000	0	-0.35	28	28
NFAT1-c-4/MAF/IRF4	-0.31	0.47	-10000	0	-0.95	325	325
DGKA	-0.019	0.21	-10000	0	-0.61	93	93
CREM	0	0.001	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.39	0.52	-10000	0	-1.1	353	353
CTLA4	-0.089	0.24	-10000	0	-0.59	118	118
NFAT1-c-4 (dimer)/EGR1	-0.42	0.57	-10000	0	-1.2	350	350
NFAT1-c-4 (dimer)/EGR4	-0.29	0.45	-10000	0	-0.91	340	340
FOS	-0.23	0.37	-10000	0	-0.8	325	325
IFNG	-0.15	0.27	-10000	0	-0.82	117	117
T cell activation	-0.17	0.35	-10000	0	-0.8	195	195
MAF	-0.001	0.024	-10000	0	-0.79	1	1
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.16	0.36	0.69	285	-10000	0	285
TNF	-0.31	0.52	-10000	0	-1	334	334
FASLG	-0.36	0.68	-10000	0	-1.3	339	339
TBX21	-0.022	0.16	-10000	0	-0.66	55	55
BATF3	-0.002	0.03	-10000	0	-0.39	5	5
PRKCQ	-0.025	0.16	-10000	0	-0.69	59	59
PTPN1	-0.02	0.21	-10000	0	-0.59	107	107
NFAT1-c-4/ICER1	-0.29	0.44	-10000	0	-0.91	339	339
GATA3	-0.035	0.16	-10000	0	-0.58	69	69
T-helper 1 cell differentiation	-0.15	0.26	-10000	0	-0.8	117	117
IL2RA	-0.24	0.34	-10000	0	-0.98	127	127
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.018	0.21	-10000	0	-0.57	113	113
E2F1	-0.079	0.14	-10000	0	-0.28	348	348
PPARG	-0.19	0.34	-10000	0	-0.79	263	263
SLC3A2	-0.018	0.21	-10000	0	-0.58	112	112
IRF4	-0.072	0.22	-10000	0	-0.73	107	107
PTGS2	-0.47	0.65	-10000	0	-1.2	403	403
CSF2	-0.36	0.55	-10000	0	-1.1	330	330
JunB/Fra1/NFAT1-c-4	-0.28	0.43	-10000	0	-0.88	322	322
IL4	-0.12	0.32	-10000	0	-0.9	113	113
IL5	-0.36	0.55	-10000	0	-1.1	328	328
IL2	-0.17	0.36	-10000	0	-0.81	193	193
IL3	-0.063	0.065	-10000	0	-10000	0	0
RNF128	-0.047	0.27	-10000	0	-0.85	111	111
NFATC1	-0.16	0.36	-10000	0	-0.7	279	279
CDK4	0.084	0.23	0.56	80	-10000	0	80
PTPRK	-0.023	0.23	-10000	0	-0.68	86	86
IL8	-0.36	0.56	-10000	0	-1.1	332	332
POU2F1	0.001	0.01	-10000	0	-0.29	1	1

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.024	0.079	0.37	1	-10000	0	1
SMARCC2	0.012	0.009	-10000	0	-10000	0	0
SMARCC1	0.012	0.009	-10000	0	-10000	0	0
TBX21	-0.13	0.25	-10000	0	-0.69	113	113
SUMO2	0	0.01	-10000	0	-0.29	1	1
STAT1 (dimer)	0.014	0.04	-10000	0	-0.29	19	19
FKBP4	-0.002	0.027	-10000	0	-0.29	9	9
FKBP5	-0.014	0.1	-10000	0	-0.68	23	23
GR alpha/HSP90/FKBP51/HSP90	0.11	0.14	0.31	125	-0.4	21	146
PRL	-0.087	0.12	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/TIF2	0.26	0.3	0.54	451	-0.55	30	481
RELA	-0.039	0.083	-10000	0	-0.3	1	1
FGG	0.23	0.22	0.48	348	-0.48	3	351
GR beta/TIF2	0.1	0.2	0.35	107	-0.56	55	162
IFNG	-0.42	0.35	-10000	0	-0.74	515	515
apoptosis	-0.27	0.3	0.59	3	-0.65	308	311
CREB1	-0.009	0.032	-10000	0	-10000	0	0
histone acetylation	0.022	0.14	0.39	45	-0.37	39	84
BGLAP	-0.1	0.15	-10000	0	-0.53	17	17
GR/PKAc	0.11	0.12	0.32	71	-0.46	4	75
NF kappa B1 p50/RelA	-0.066	0.15	-10000	0	-0.42	38	38
SMARCD1	0.012	0.009	-10000	0	-10000	0	0
MDM2	0.12	0.1	0.26	247	-10000	0	247
GATA3	-0.026	0.16	-10000	0	-0.58	69	69
AKT1	0	0.004	-10000	0	-10000	0	0
CSF2	-0.04	0.11	-10000	0	-0.6	7	7
GSK3B	0	0.004	-10000	0	-10000	0	0
NR1I3	-0.21	0.26	0.56	3	-0.62	170	173
CSN2	0.19	0.18	0.41	249	-0.53	1	250
BRG1/BAF155/BAF170/BAF60A	-0.002	0.031	-10000	0	-0.46	5	5
NFATC1	0.001	0.042	-10000	0	-0.79	3	3
POU2F1	0.007	0.013	-10000	0	-0.29	1	1
CDKN1A	0.046	0.072	-10000	0	-1.5	2	2
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.007	0.008	-10000	0	-10000	0	0
SFN	-0.016	0.099	-10000	0	-0.51	35	35
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.1	0.14	0.33	64	-0.4	19	83
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.37	0.43	0.54	3	-0.88	399	402
JUN	-0.32	0.29	-10000	0	-0.6	448	448
IL4	-0.13	0.16	-10000	0	-0.56	23	23
CDK5R1	-0.008	0.05	-10000	0	-0.3	31	31
PRKACA	0	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.41	0.4	-10000	0	-0.74	581	581
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.11	0.13	0.32	84	-0.37	17	101
cortisol/GR alpha (monomer)	0.34	0.32	0.63	503	-0.51	3	506
NCOA2	-0.038	0.17	-10000	0	-0.79	53	53
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.28	0.38	-10000	0	-0.86	325	325
AP-1/NFAT1-c-4	-0.65	0.52	-10000	0	-1	650	650
AFP	-0.61	0.7	-10000	0	-1.5	376	376
SUV420H1	0	0	-10000	0	-10000	0	0
IRF1	0.19	0.16	0.51	63	-10000	0	63
TP53	0.032	0.023	-10000	0	-0.5	2	2
PPP5C	0	0	-10000	0	-10000	0	0
KRT17	-0.82	0.8	-10000	0	-1.6	500	500
KRT14	-0.81	0.77	-10000	0	-1.5	567	567
TBP	0.019	0.006	-10000	0	-10000	0	0
CREBBP	0.14	0.14	0.29	352	-10000	0	352
HDAC1	0	0.004	-10000	0	-10000	0	0
HDAC2	0.001	0.004	-10000	0	-10000	0	0
AP-1	-0.66	0.52	-10000	0	-1	651	651
MAPK14	0	0.003	-10000	0	-10000	0	0
MAPK10	-0.12	0.29	-10000	0	-0.8	170	170
MAPK11	-0.002	0.042	-10000	0	-0.8	3	3
KRT5	-0.92	0.81	-10000	0	-1.7	575	575
interleukin-1 receptor activity	-0.001	0.003	-10000	0	-10000	0	0
NCOA1	0.014	0.024	-10000	0	-0.78	1	1
STAT1	0.014	0.04	-10000	0	-0.29	19	19
CGA	-0.16	0.18	-10000	0	-0.52	93	93
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.2	0.18	0.37	514	-10000	0	514
MAPK3	0	0.003	-10000	0	-10000	0	0
MAPK1	0	0.003	-10000	0	-10000	0	0
ICAM1	-0.18	0.25	-10000	0	-0.63	150	150
NFKB1	-0.039	0.083	-10000	0	-0.3	1	1
MAPK8	-0.23	0.22	-10000	0	-0.44	448	448
MAPK9	0	0.003	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.29	0.32	0.59	3	-0.69	309	312
BAX	0.048	0.032	-10000	0	-10000	0	0
POMC	-0.19	0.31	-10000	0	-0.92	94	94
EP300	0.14	0.14	0.28	533	-0.25	1	534
cortisol/GR alpha (dimer)/p53	0.31	0.26	0.56	460	-0.56	1	461
proteasomal ubiquitin-dependent protein catabolic process	0.086	0.079	0.24	60	-10000	0	60
SGK1	0.22	0.2	-10000	0	-1.2	6	6
IL13	-0.31	0.28	-10000	0	-0.65	306	306
IL6	-0.49	0.62	-10000	0	-1.3	405	405
PRKACG	0	0	-10000	0	-10000	0	0
IL5	-0.27	0.23	-10000	0	-0.77	52	52
IL2	-0.41	0.35	-10000	0	-0.76	457	457
CDK5	-0.002	0.024	-10000	0	-0.3	7	7
PRKACB	-0.016	0.077	-10000	0	-0.33	53	53
HSP90AA1	0	0.009	-10000	0	-0.29	1	1
IL8	-0.2	0.3	-10000	0	-0.83	115	115
CDK5R1/CDK5	-0.007	0.036	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	-0.055	0.1	-10000	0	-0.52	8	8
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.28	0.24	0.52	445	-0.5	2	447
SMARCA4	0.012	0.013	-10000	0	-0.29	1	1
chromatin remodeling	0.2	0.16	0.38	346	-0.34	2	348
NF kappa B1 p50/RelA/Cbp	0.06	0.17	0.34	103	-0.45	2	105
JUN (dimer)	-0.32	0.29	-10000	0	-0.6	449	449
YWHAH	0	0	-10000	0	-10000	0	0
VIPR1	-0.13	0.25	-10000	0	-0.81	84	84
NR3C1	0.2	0.2	0.44	314	-0.49	9	323
NR4A1	-0.056	0.23	-10000	0	-0.72	108	108
TIF2/SUV420H1	-0.029	0.13	-10000	0	-0.6	53	53
MAPKKK cascade	-0.27	0.3	0.59	3	-0.65	308	311
cortisol/GR alpha (dimer)/Src-1	0.3	0.26	0.55	468	-0.57	1	469
PBX1	0.005	0.037	-10000	0	-0.78	2	2
POU1F1	0.003	0.015	-10000	0	-0.29	1	1
SELE	-0.22	0.36	-10000	0	-1	120	120
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.2	0.16	0.38	343	-0.34	2	345
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.28	0.24	0.52	445	-0.5	2	447
mol:cortisol	0.2	0.2	0.37	518	-0.2	1	519
MMP1	-0.22	0.11	-10000	0	-10000	0	0

×

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	-0.46	0.46	-10000	0	-1.1	270	270
STAT6 (cleaved dimer)	-0.5	0.45	-10000	0	-0.97	423	423
IGHG1	-0.16	0.16	-10000	0	-0.36	92	92
IGHG3	-0.45	0.44	-10000	0	-0.94	389	389
AKT1	-0.21	0.24	-10000	0	-0.65	96	96
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.15	0.2	-10000	0	-0.58	65	65
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.22	0.24	-10000	0	-0.63	117	117
THY1	-0.46	0.46	-10000	0	-1.1	234	234
MYB	-0.017	0.11	-10000	0	-0.73	26	26
HMGA1	-0.014	0.063	-10000	0	-0.29	53	53
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.28	0.29	-10000	0	-0.65	265	265
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.21	0.23	-10000	0	-0.58	115	115
SP1	0.018	0.006	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
SOCS5	0.024	0.029	-10000	0	-0.76	1	1
STAT6 (dimer)/ETS1	-0.48	0.44	-10000	0	-1	348	348
SOCS1	-0.3	0.31	-10000	0	-0.74	207	207
SOCS3	-0.23	0.26	-10000	0	-0.81	71	71
FCER2	-0.59	0.64	-10000	0	-1.4	377	377
PARP14	0.004	0.018	-10000	0	-0.3	3	3
CCL17	-0.47	0.46	-10000	0	-1.1	255	255
GRB2	0	0.009	-10000	0	-0.29	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.17	0.19	-10000	0	-0.59	29	29
T cell proliferation	-0.46	0.48	-10000	0	-1.1	278	278
IL4R/JAK1	-0.46	0.46	-10000	0	-1.1	259	259
EGR2	-0.6	0.63	-10000	0	-1.4	355	355
JAK2	-0.008	0.035	-10000	0	-0.81	1	1
JAK3	0.01	0.035	-10000	0	-0.29	14	14
PIK3R1	-0.009	0.086	-10000	0	-0.79	13	13
JAK1	0.004	0.026	-10000	0	-0.79	1	1
COL1A2	-0.14	0.16	-10000	0	-1.6	3	3
CCL26	-0.46	0.46	-10000	0	-1.1	276	276
IL4R	-0.49	0.49	-10000	0	-1.2	278	278
PTPN6	0.022	0.018	-10000	0	-0.28	2	2
IL13RA2	-0.46	0.46	-10000	0	-1.1	253	253
IL13RA1	-0.007	0.025	-10000	0	-10000	0	0
IRF4	-0.22	0.48	-10000	0	-1.5	115	115
ARG1	-0.11	0.12	-10000	0	-10000	0	0
CBL	-0.26	0.28	-10000	0	-0.64	221	221
GTF3A	0.013	0.016	-10000	0	-0.29	2	2
PIK3CA	0	0.009	-10000	0	-0.29	1	1
IL13RA1/JAK2	-0.014	0.041	-10000	0	-0.62	1	1
IRF4/BCL6	-0.2	0.43	-10000	0	-1.4	119	119
CD40LG	-0.031	0.18	-10000	0	-0.72	66	66
MAPK14	-0.26	0.28	-10000	0	-0.66	204	204
mitosis	-0.2	0.23	-10000	0	-0.61	96	96
STAT6	-0.53	0.55	-10000	0	-1.2	347	347
SPI1	0.007	0.022	-10000	0	-0.29	5	5
RPS6KB1	-0.19	0.22	-10000	0	-0.6	84	84
STAT6 (dimer)	-0.53	0.55	-10000	0	-1.2	347	347
STAT6 (dimer)/PARP14	-0.51	0.51	-10000	0	-1.1	370	370
mast cell activation	0.012	0.012	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.2	0.23	-10000	0	-0.58	117	117
FRAP1	-0.21	0.24	-10000	0	-0.65	96	96
LTA	-0.47	0.46	-10000	0	-1.1	285	285
FES	-0.002	0.041	-10000	0	-0.79	3	3
T-helper 1 cell differentiation	0.52	0.52	1.1	365	-10000	0	365
CCL11	-0.49	0.44	-10000	0	-1.1	283	283
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.2	0.23	-10000	0	-0.6	106	106
IL2RG	-0.004	0.088	-10000	0	-0.36	53	53
IL10	-0.46	0.46	-10000	0	-1.1	246	246
IRS1	-0.033	0.16	-10000	0	-0.79	45	45
IRS2	-0.033	0.16	-10000	0	-0.79	45	45
IL4	-0.11	0.11	-10000	0	-10000	0	0
IL5	-0.47	0.46	-10000	0	-1.2	230	230
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.38	0.36	-10000	0	-0.82	310	310
COL1A1	-0.18	0.17	-10000	0	-1.7	1	1
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.46	0.48	-10000	0	-1.2	212	212
IL2R gamma/JAK3	-0.011	0.071	-10000	0	-0.45	20	20
TFF3	-0.56	0.58	-10000	0	-1.3	324	324
ALOX15	-0.54	0.57	-10000	0	-1.3	304	304
MYBL1	-0.041	0.1	-10000	0	-0.29	154	154
T-helper 2 cell differentiation	-0.39	0.38	-10000	0	-0.84	345	345
SHC1	0	0	-10000	0	-10000	0	0
CEBPB	0.009	0.009	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.21	0.24	-10000	0	-0.57	139	139
mol:PI-3-4-5-P3	-0.21	0.24	-10000	0	-0.65	96	96
PI3K	-0.22	0.26	-10000	0	-0.69	96	96
DOK2	-0.003	0.045	-10000	0	-0.51	7	7
ETS1	0.019	0.054	-10000	0	-0.75	5	5
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.15	0.18	-10000	0	-0.68	15	15
ITGB3	-0.48	0.5	-10000	0	-1.1	296	296
PIGR	-0.99	0.75	-10000	0	-1.5	691	691
IGHE	0.046	0.04	-10000	0	-10000	0	0
MAPKKK cascade	-0.15	0.18	-10000	0	-0.66	15	15
BCL6	0.001	0.06	-10000	0	-0.79	6	6
OPRM1	-0.47	0.46	-10000	0	-1.2	226	226
RETNLB	-0.47	0.46	-10000	0	-1.1	305	305
SELP	-0.63	0.68	-10000	0	-1.5	335	335
AICDA	-0.45	0.44	-10000	0	-1.1	267	267

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0	0	-9999	-10000	0	0
VLDLR	-0.024	0.14	-9999	-0.79	33	33
LRPAP1	0	0	-9999	-10000	0	0
NUDC	0	0	-9999	-10000	0	0
RELN/LRP8	-0.32	0.26	-9999	-0.54	651	651
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0	0.009	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.28	0.25	-9999	-0.48	651	651
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	-0.017	0.069	-9999	-10000	0	0
IQGAP1	0	0	-9999	-10000	0	0
PLA2G7	-0.015	0.091	-9999	-0.43	39	39
CALM1	0	0	-9999	-10000	0	0
DYNLT1	0	0.009	-9999	-0.29	1	1
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.019	0.057	-9999	-10000	0	0
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0	0	-9999	-10000	0	0
CDK5R1	-0.008	0.049	-9999	-0.29	31	31
LIS1/Poliovirus Protein 3A	0	0	-9999	-10000	0	0
CDK5R2	-0.044	0.1	-9999	-0.29	165	165
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.33	0.27	-9999	-0.55	660	660
YWHAE	0	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.23	0.19	-9999	-0.45	185	185
MAP1B	-0.008	0.053	-9999	-0.37	22	22
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.26	0.21	-9999	-0.42	651	651
RELN	-0.47	0.39	-9999	-0.79	654	654
PAFAH/LIS1	-0.009	0.056	-9999	-0.52	11	11
LIS1/CLIP170	0	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.18	0.15	-9999	-0.43	4	4
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.2	0.17	-9999	-0.33	663	663
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.25	0.2	-9999	-0.48	185	185
LIS1/IQGAP1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.022	0	-9999	-10000	0	0
PAFAH1B3	-0.035	0.095	-9999	-0.29	130	130
PAFAH1B2	-0.004	0.058	-9999	-0.79	6	6
MAP1B/LIS1/Dynein heavy chain	-0.005	0.033	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.22	0.18	-9999	-0.46	99	99
LRP8	-0.031	0.09	-9999	-10000	0	0
NDEL1/Katanin 60	-0.23	0.19	-9999	-0.45	186	186
P39/CDK5	-0.27	0.22	-9999	-0.45	651	651
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0	0	-9999	-10000	0	0
CDK5	-0.26	0.24	-9999	-0.45	651	651
PPP2R5D	0	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0	-9999	-10000	0	0
CSNK2A1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.28	0.24	-9999	-0.46	660	660
RELN/VLDLR	-0.31	0.25	-9999	-0.5	660	660
CDC42	0	0	-9999	-10000	0	0

×

Arf6 signaling events

Figure S14. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S14. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.004	0.043	-9999	-0.64	4	4
ARNO/beta Arrestin1-2	-0.12	0.19	-9999	-0.43	251	251
EGFR	-0.3	0.38	-9999	-0.78	414	414
EPHA2	-0.004	0.058	-9999	-0.79	6	6
USP6	0	0	-9999	-10000	0	0
IQSEC1	0	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.34	0.35	-9999	-0.66	555	555
ARRB2	-0.051	0.15	-9999	-0.44	148	148
mol:GTP	0.017	0.018	-9999	-0.15	5	5
ARRB1	-0.002	0.035	-9999	-0.62	3	3
FBXO8	0	0	-9999	-10000	0	0
TSHR	-0.037	0.16	-9999	-0.74	54	54
EGF	-0.16	0.31	-9999	-0.78	216	216
somatostatin receptor activity	0	0	-9999	-0.001	383	383
ARAP2	-0.004	0.058	-9999	-0.79	6	6
mol:GDP	-0.14	0.18	-9999	-0.34	352	352
mol:PI-3-4-5-P3	0	0	-9999	-0.001	339	339
ITGA2B	-0.019	0.079	-9999	-0.32	64	64
ARF6	0	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.003	0.036	-9999	-0.47	6	6
ADAP1	-0.005	0.05	-9999	-0.41	13	13
KIF13B	-0.001	0.034	-9999	-0.79	2	2
HGF/MET	-0.14	0.28	-9999	-0.64	240	240
PXN	0	0	-9999	-10000	0	0
ARF6/GTP	-0.13	0.15	-9999	-0.31	379	379
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.29	0.31	-9999	-0.58	555	555
ADRB2	-0.18	0.33	-9999	-0.79	250	250
receptor agonist activity	0	0	-9999	0	382	382
actin filament binding	0	0	-9999	-0.001	372	372
SRC	0	0.009	-9999	-0.29	1	1
ITGB3	-0.029	0.15	-9999	-0.74	42	42
GNAQ	-0.002	0.041	-9999	-0.79	3	3
EFA6/PI-4-5-P2	0	0.001	-9999	-0.001	349	349
ARF6/GDP	-0.014	0.083	-9999	-0.42	18	18
ARF6/GDP/GULP/ACAP1	-0.15	0.2	-9999	-0.51	187	187
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.025	0.095	-9999	-0.48	41	41
ACAP1	-0.02	0.095	-9999	-0.38	57	57
ACAP2	0	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	-0.088	0.22	-9999	-0.65	148	148
EFNA1	0	0.009	-9999	-0.29	1	1
HGF	-0.053	0.2	-9999	-0.78	75	75
CYTH3	0.01	0.019	-9999	-0.61	1	1
CYTH2	0.006	0.002	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	0	300	300
endosomal lumen acidification	0	0	-9999	-0.001	303	303
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.053	0.2	-9999	-0.79	73	73
GNAQ/ARNO	0.004	0.025	-9999	-0.45	3	3
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	378	378
MET	-0.14	0.3	-9999	-0.79	188	188
GNA14	-0.013	0.085	-9999	-0.45	32	32
GNA15	-0.003	0.033	-9999	-0.36	8	8
GIT1	-0.001	0.02	-9999	-0.29	5	5
mol:PI-4-5-P2	0	0	-9999	-0.001	353	353
GNA11	-0.002	0.041	-9999	-0.79	3	3
LHCGR	-0.11	0.27	-9999	-0.79	148	148
AGTR1	-0.21	0.34	-9999	-0.69	327	327
desensitization of G-protein coupled receptor protein signaling pathway	-0.088	0.22	-9999	-0.65	148	148
IPCEF1/ARNO	-0.24	0.25	-9999	-0.46	555	555
alphaIIb/beta3 Integrin	-0.034	0.12	-9999	-0.62	41	41

×

Wnt 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
Noncanonical Wnts/FZD	-0.16	0.24	-9999	-0.44	381	381
FZD6	-0.007	0.075	-9999	-0.79	10	10
WNT6	-0.16	0.31	-9999	-0.69	255	255
WNT4	-0.022	0.12	-9999	-0.55	43	43
FZD3	-0.011	0.092	-9999	-0.79	15	15
WNT5A	-0.016	0.1	-9999	-0.61	28	28
WNT11	-0.16	0.32	-9999	-0.76	235	235

×

FOXM1 transcription factor network

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
NFATC3	-0.24	0.44	-9999	-0.95	158	158
PLK1	-0.087	0.11	-9999	-10000	0	0
BIRC5	-0.1	0.1	-9999	-10000	0	0
HSPA1B	-0.24	0.44	-9999	-0.98	141	141
MAP2K1	0.008	0.03	-9999	-10000	0	0
BRCA2	-0.24	0.44	-9999	-0.98	145	145
FOXM1	-0.29	0.52	-9999	-1.1	212	212
XRCC1	-0.24	0.44	-9999	-0.98	141	141
FOXM1B/p19	-0.29	0.42	-9999	-0.94	233	233
Cyclin D1/CDK4	-0.23	0.41	-9999	-0.91	144	144
CDC2	-0.26	0.46	-9999	-0.94	215	215
TGFA	-0.22	0.42	-9999	-0.92	154	154
SKP2	-0.24	0.44	-9999	-1	121	121
CCNE1	-0.056	0.13	-9999	-0.3	223	223
CKS1B	-0.24	0.44	-9999	-0.98	141	141
RB1	-0.12	0.13	-9999	-1.1	2	2
FOXM1C/SP1	-0.3	0.45	-9999	-0.99	219	219
AURKB	-0.08	0.11	-9999	-10000	0	0
CENPF	-0.27	0.46	-9999	-0.97	193	193
CDK4	0.007	0.022	-9999	-0.3	4	4
MYC	-0.22	0.41	-9999	-0.88	172	172
CHEK2	0.007	0.033	-9999	-0.32	2	2
ONECUT1	-0.24	0.43	-9999	-0.94	164	164
CDKN2A	-0.039	0.12	-9999	-0.29	177	177
LAMA4	-0.24	0.44	-9999	-1	140	140
FOXM1B/HNF6	-0.27	0.49	-9999	-1.1	147	147
FOS	-0.44	0.67	-9999	-1.3	346	346
SP1	0	0	-9999	-10000	0	0
CDC25B	-0.24	0.44	-9999	-0.98	143	143
response to radiation	-0.007	0.03	-9999	-10000	0	0
CENPB	-0.24	0.44	-9999	-0.98	138	138
CENPA	-0.27	0.46	-9999	-0.98	185	185
NEK2	-0.29	0.45	-9999	-0.98	188	188
HIST1H2BA	-0.25	0.44	-9999	-0.98	141	141
CCNA2	-0.11	0.15	-9999	-0.3	426	426
EP300	0	0	-9999	-10000	0	0
CCNB1/CDK1	-0.28	0.49	-9999	-1.1	184	184
CCNB2	-0.27	0.46	-9999	-0.98	192	192
CCNB1	-0.26	0.46	-9999	-0.99	189	189
ETV5	-0.24	0.44	-9999	-0.98	140	140
ESR1	-0.34	0.58	-9999	-1.3	238	238
CCND1	-0.23	0.42	-9999	-0.93	144	144
GSK3A	0.014	0.021	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	-0.081	0.14	-9999	-0.33	189	189
CDK2	0.006	0.009	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.01	0.036	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.33	0.38	-9999	-0.92	240	240
GAS1	-0.28	0.5	-9999	-1.1	194	194
MMP2	-0.24	0.44	-9999	-1	141	141
RB1/FOXM1C	-0.24	0.44	-9999	-0.94	180	180
CREBBP	0	0	-9999	-10000	0	0

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.053	0.067	-9999	-10000	0	0
STMN1	-0.11	0.12	-9999	-0.37	81	81
Aurora B/RasGAP/Survivin	-0.18	0.13	-9999	-10000	0	0
Chromosomal passenger complex/Cul3 protein complex	-0.16	0.15	-9999	-0.33	438	438
BIRC5	-0.21	0.14	-9999	-0.3	779	779
DES	-0.29	0.34	-9999	-0.66	496	496
Aurora C/Aurora B/INCENP	-0.069	0.076	-9999	-0.62	1	1
Aurora B/TACC1	-0.1	0.13	-9999	-0.61	41	41
Aurora B/PP2A	-0.099	0.097	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.008	0.017	-9999	-10000	0	0
mitotic metaphase/anaphase transition	-0.003	0.003	-9999	-10000	0	0
NDC80	-0.21	0.18	-9999	-0.37	549	549
Cul3 protein complex	-0.21	0.26	-9999	-0.52	438	438
KIF2C	-0.046	0.034	-9999	-10000	0	0
PEBP1	0.002	0.005	-9999	-10000	0	0
KIF20A	-0.22	0.13	-9999	-0.3	819	819
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.099	0.097	-9999	-10000	0	0
SEPT1	-0.01	0.053	-9999	-0.29	37	37
SMC2	0	0	-9999	-10000	0	0
SMC4	-0.004	0.034	-9999	-0.29	15	15
NSUN2/NPM1/Nucleolin	0.005	0.02	-9999	-10000	0	0
PSMA3	0	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.003	0.002	-9999	-10000	0	0
H3F3B	-0.034	0.046	-9999	-10000	0	0
AURKB	-0.16	0.15	-9999	-0.3	625	625
AURKC	-0.005	0.043	-9999	-0.32	18	18
CDCA8	-0.099	0.14	-9999	-0.3	370	370
cytokinesis	-0.11	0.08	-9999	-10000	0	0
Aurora B/Septin1	-0.099	0.089	-9999	-10000	0	0
AURKA	-0.14	0.15	-9999	-0.3	505	505
INCENP	0.003	0.005	-9999	-10000	0	0
KLHL13	-0.32	0.39	-9999	-0.79	437	437
BUB1	-0.2	0.14	-9999	-0.3	731	731
hSgo1/Aurora B/Survivin	-0.26	0.18	-9999	-0.41	538	538
EVI5	0.009	0.004	-9999	-10000	0	0
RhoA/GTP	-0.1	0.1	-9999	-0.34	35	35
SGOL1	-0.18	0.14	-9999	-0.29	681	681
CENPA	-0.06	0.065	-9999	-10000	0	0
NCAPG	-0.14	0.15	-9999	-0.29	529	529
Aurora B/HC8 Proteasome	-0.099	0.097	-9999	-10000	0	0
NCAPD2	-0.002	0.025	-9999	-0.29	8	8
Aurora B/PP1-gamma	-0.099	0.097	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
NCAPH	-0.11	0.14	-9999	-10000	0	0
NPM1	-0.019	0.025	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
KLHL9	-0.001	0.034	-9999	-0.79	2	2
mitotic prometaphase	-0.006	0.005	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.099	0.097	-9999	-10000	0	0
PPP1CC	0	0	-9999	-10000	0	0
Centraspindlin	-0.12	0.11	-9999	-0.37	38	38
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.019	0.025	-9999	-10000	0	0
MYLK	-0.088	0.15	-9999	-0.47	139	139
KIF23	-0.088	0.14	-9999	-0.3	336	336
VIM	-0.095	0.1	-9999	-0.68	2	2
RACGAP1	-0.007	0.059	-9999	-0.3	42	42
mitosis	0	0	-9999	-10000	0	0
NCL	-0.019	0.025	-9999	-10000	0	0
Chromosomal passenger complex	-0.085	0.079	-9999	-10000	0	0
Chromosomal passenger complex/EVI5	-0.16	0.18	-9999	-0.37	211	211
TACC1	-0.03	0.15	-9999	-0.79	41	41
PPP2R5D	0	0	-9999	-10000	0	0
CUL3	0	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

Endothelins

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.008	0.19	-9999	-0.59	88	88
PTK2B	0.005	0.006	-9999	-10000	0	0
mol:Ca2+	0.022	0.2	-9999	-0.95	33	33
EDN1	-0.034	0.24	-9999	-0.81	85	85
EDN3	-0.37	0.39	-9999	-0.79	512	512
EDN2	-0.076	0.14	-9999	-0.31	268	268
HRAS/GDP	-0.029	0.21	-9999	-0.54	101	101
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.002	0.14	-9999	-0.42	63	63
ADCY4	-0.14	0.29	-9999	-0.55	313	313
ADCY5	-0.27	0.36	-9999	-0.6	513	513
ADCY6	-0.13	0.26	-9999	-0.52	295	295
ADCY7	-0.13	0.26	-9999	-0.52	295	295
ADCY1	-0.15	0.29	-9999	-0.56	310	310
ADCY2	-0.17	0.32	-9999	-0.59	327	327
ADCY3	-0.13	0.26	-9999	-0.52	295	295
ADCY8	-0.14	0.27	-9999	-0.53	295	295
ADCY9	-0.13	0.26	-9999	-0.52	295	295
arachidonic acid secretion	-0.1	0.3	-9999	-0.59	210	210
ETB receptor/Endothelin-1/Gq/GTP	-0.034	0.18	-9999	-0.39	164	164
GNAO1	-0.03	0.13	-9999	-0.49	67	67
HRAS	-0.002	0.027	-9999	-0.29	9	9
ETA receptor/Endothelin-1/G12/GTP	0.04	0.21	-9999	-0.55	88	88
ETA receptor/Endothelin-1/Gs/GTP	-0.087	0.32	-9999	-0.56	295	295
mol:GTP	-0.001	0.006	-9999	-10000	0	0
COL3A1	-0.017	0.2	-9999	-0.59	88	88
EDNRB	-0.073	0.24	-9999	-0.79	113	113
response to oxidative stress	0	0	-9999	-10000	0	0
CYSLTR2	-0.022	0.24	-9999	-0.68	104	104
CYSLTR1	-0.019	0.23	-9999	-0.66	101	101
SLC9A1	0.003	0.1	-9999	-0.31	72	72
mol:GDP	-0.037	0.22	-9999	-0.56	108	108
SLC9A3	-0.051	0.28	-9999	-0.63	183	183
RAF1	-0.084	0.25	-9999	-0.56	155	155
JUN	0.029	0.18	-9999	-0.84	29	29
JAK2	-0.008	0.2	-9999	-0.59	88	88
mol:IP3	-0.029	0.18	-9999	-0.52	75	75
ETA receptor/Endothelin-1	0.038	0.25	-9999	-0.68	88	88
PLCB1	-0.052	0.21	-9999	-0.79	82	82
PLCB2	0.007	0.027	-9999	-0.54	2	2
ETA receptor/Endothelin-3	-0.27	0.31	-9999	-0.6	510	510
FOS	-0.25	0.49	-9999	-0.99	331	331
Gai/GDP	-0.016	0.16	-9999	-0.79	28	28
CRK	0.005	0.006	-9999	-10000	0	0
mol:Ca ++	-0.049	0.25	-9999	-0.67	114	114
BCAR1	0.005	0.006	-9999	-10000	0	0
PRKCB1	-0.031	0.17	-9999	-0.47	91	91
GNAQ	0.008	0.043	-9999	-0.8	3	3
GNAZ	-0.007	0.071	-9999	-0.79	9	9
GNAL	-0.19	0.34	-9999	-0.79	259	259
Gs family/GDP	-0.17	0.26	-9999	-0.57	261	261
ETA receptor/Endothelin-1/Gq/GTP	0.018	0.13	-9999	-0.4	57	57
MAPK14	-0.032	0.17	-9999	-0.49	89	89
TRPC6	0.02	0.22	-9999	-1.1	32	32
GNAI2	0	0	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
GNAI1	-0.045	0.18	-9999	-0.79	62	62
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.041	0.18	-9999	-0.43	138	138
ETB receptor/Endothelin-2	-0.11	0.21	-9999	-0.65	120	120
ETB receptor/Endothelin-3	-0.34	0.34	-9999	-0.65	568	568
ETB receptor/Endothelin-1	-0.081	0.27	-9999	-0.66	183	183
MAPK3	-0.19	0.41	-9999	-0.79	335	335
MAPK1	-0.19	0.41	-9999	-0.79	335	335
Rac1/GDP	-0.027	0.2	-9999	-0.53	102	102
cAMP biosynthetic process	-0.17	0.3	-9999	-0.6	304	304
MAPK8	0.02	0.19	-9999	-0.75	40	40
SRC	0	0.009	-9999	-0.29	1	1
ETB receptor/Endothelin-1/Gi/GTP	-0.049	0.19	-9999	-0.53	91	91
p130Cas/CRK/Src/PYK2	-0.014	0.22	-9999	-0.62	76	76
mol:K +	0	0	-9999	-10000	0	0
G12/GDP	-0.027	0.2	-9999	-0.53	102	102
COL1A2	-0.054	0.25	-9999	-0.69	103	103
EntrezGene:2778	0	0	-9999	-10000	0	0
ETA receptor/Endothelin-2	-0.029	0.12	-9999	-0.44	20	20
mol:DAG	-0.029	0.18	-9999	-0.5	83	83
MAP2K2	-0.13	0.32	-9999	-0.57	341	341
MAP2K1	-0.13	0.32	-9999	-0.57	339	339
EDNRA	0.027	0.07	-9999	-0.43	5	5
positive regulation of muscle contraction	-0.009	0.17	-9999	-0.51	88	88
Gq family/GDP	-0.073	0.16	-9999	-0.6	62	62
HRAS/GTP	-0.052	0.21	-9999	-0.49	136	136
PRKCH	-0.023	0.17	-9999	-0.53	66	66
RAC1	0	0	-9999	-10000	0	0
PRKCA	-0.035	0.2	-9999	-0.58	84	84
PRKCB	-0.035	0.2	-9999	-0.57	79	79
PRKCE	-0.023	0.17	-9999	-0.52	67	67
PRKCD	-0.024	0.17	-9999	-0.51	71	71
PRKCG	-0.033	0.18	-9999	-0.52	76	76
regulation of vascular smooth muscle contraction	-0.29	0.57	-9999	-1.1	331	331
PRKCQ	-0.045	0.21	-9999	-0.57	108	108
PLA2G4A	-0.12	0.33	-9999	-0.66	210	210
GNA14	-0.004	0.088	-9999	-0.45	32	32
GNA15	0.007	0.035	-9999	-0.36	8	8
GNA12	0	0	-9999	-10000	0	0
GNA11	0.007	0.042	-9999	-0.79	3	3
Rac1/GTP	0.041	0.2	-9999	-0.55	88	88
MMP1	-0.13	0.13	-9999	-10000	0	0

×

Ephrin B reverse signaling

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
EFNB2	0	0	-10000	0	-10000	0	0
EPHB2	-0.003	0.039	-10000	0	-0.29	19	19
EFNB1	0.017	0.05	-10000	0	-0.6	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.16	0.2	-10000	0	-0.41	427	427
Ephrin B2/EPHB1-2	-0.19	0.23	-10000	0	-0.48	426	426
neuron projection morphogenesis	-0.15	0.19	-10000	0	-0.39	427	427
Ephrin B1/EPHB1-2/Tiam1	-0.18	0.22	-10000	0	-0.44	427	427
DNM1	-0.005	0.064	-10000	0	-0.73	8	8
cell-cell signaling	-0.001	0.002	-10000	0	-10000	0	0
MAP2K4	-0.003	0.13	-10000	0	-0.74	33	33
YES1	-0.025	0.17	-10000	0	-0.98	32	32
Ephrin B1/EPHB1-2/NCK2	-0.17	0.22	-10000	0	-0.44	427	427
PI3K	-0.028	0.14	-10000	0	-0.68	44	44
mol:GDP	-0.17	0.22	-10000	0	-0.44	427	427
ITGA2B	-0.019	0.079	-10000	0	-0.32	64	64
endothelial cell proliferation	0	0.005	-10000	0	-10000	0	0
FYN	-0.025	0.16	-10000	0	-0.97	32	32
MAP3K7	-0.022	0.14	-10000	0	-0.79	32	32
FGR	-0.027	0.17	-10000	0	-0.98	32	32
TIAM1	-0.001	0.018	-10000	0	-0.29	4	4
PIK3R1	-0.009	0.086	-10000	0	-0.79	13	13
RGS3	0	0	-10000	0	-10000	0	0
cell adhesion	-0.046	0.16	-10000	0	-0.62	73	73
LYN	-0.025	0.16	-10000	0	-0.97	32	32
Ephrin B1/EPHB1-2/Src Family Kinases	-0.026	0.16	-10000	0	-0.92	32	32
Ephrin B1/EPHB1-2	-0.029	0.14	-10000	0	-0.86	32	32
SRC	-0.027	0.17	-10000	0	-0.98	32	32
ITGB3	-0.029	0.15	-10000	0	-0.74	42	42
EPHB1	-0.31	0.38	-10000	0	-0.79	426	426
EPHB4	0	0.009	-10000	0	-0.29	1	1
RAC1	0	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0	0.005	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.034	0.12	-10000	0	-0.62	41	41
BLK	-0.027	0.17	-10000	0	-0.98	32	32
HCK	-0.027	0.17	-10000	0	-0.98	32	32
regulation of stress fiber formation	0.17	0.22	0.44	427	-10000	0	427
MAPK8	0.002	0.14	-10000	0	-0.71	37	37
Ephrin B1/EPHB1-2/RGS3	-0.17	0.22	-10000	0	-0.44	427	427
endothelial cell migration	-0.016	0.12	-10000	0	-0.69	32	32
NCK2	0	0	-10000	0	-10000	0	0
PTPN13	-0.017	0.15	-10000	0	-0.9	32	32
regulation of focal adhesion formation	0.17	0.22	0.44	427	-10000	0	427
chemotaxis	0.17	0.22	0.44	427	-10000	0	427
PIK3CA	0	0.009	-10000	0	-0.29	1	1
Rac1/GTP	-0.16	0.2	-10000	0	-0.4	427	427
angiogenesis	-0.028	0.14	-10000	0	-0.85	32	32
LCK	-0.029	0.17	-10000	0	-0.98	32	32

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.013	0.01	-9999	-10000	0	0
RAS family/GTP	-0.11	0.14	-9999	-0.35	69	69
NFATC4	-0.088	0.16	-9999	-0.38	31	31
ERBB2IP	0.008	0.008	-9999	-10000	0	0
HSP90 (dimer)	0	0.009	-9999	-0.29	1	1
mammary gland morphogenesis	-0.15	0.19	-9999	-0.39	403	403
JUN	-0.018	0.08	-9999	-0.37	6	6
HRAS	-0.002	0.027	-9999	-0.29	9	9
DOCK7	-0.12	0.19	-9999	-0.38	242	242
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.18	0.22	-9999	-0.46	403	403
AKT1	0.008	0.005	-9999	-10000	0	0
BAD	0.018	0.006	-9999	-10000	0	0
MAPK10	-0.11	0.13	-9999	-0.35	173	173
mol:GTP	-0.001	0.001	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.16	0.2	-9999	-0.42	403	403
RAF1	-0.081	0.16	-9999	-0.44	18	18
ErbB2/ErbB3/neuregulin 2	-0.25	0.25	-9999	-0.5	528	528
STAT3	0.001	0.003	-9999	-10000	0	0
cell migration	-0.062	0.13	-9999	-0.31	93	93
mol:PI-3-4-5-P3	-0.002	0.003	-9999	-10000	0	0
cell proliferation	-0.14	0.22	-9999	-0.51	174	174
FOS	-0.16	0.26	-9999	-0.53	329	329
NRAS	-0.001	0.013	-9999	-0.3	2	2
mol:Ca2+	-0.15	0.19	-9999	-0.39	403	403
MAPK3	-0.11	0.19	-9999	-0.47	65	65
MAPK1	-0.11	0.19	-9999	-0.47	65	65
JAK2	-0.12	0.19	-9999	-0.37	404	404
NF2	-0.006	0.009	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.13	0.18	-9999	-0.36	403	403
NRG1	-0.29	0.38	-9999	-0.78	406	406
GRB2/SOS1	0	0.006	-9999	-10000	0	0
MAPK8	-0.11	0.17	-9999	-0.33	407	407
MAPK9	-0.069	0.087	-9999	-0.3	3	3
ERBB2	-0.017	0.059	-9999	-0.63	1	1
ERBB3	0	0.054	-9999	-0.8	5	5
SHC1	0.002	0.004	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
apoptosis	0.014	0.017	-9999	-10000	0	0
STAT3 (dimer)	0.001	0.003	-9999	-10000	0	0
RNF41	0.018	0.014	-9999	-10000	0	0
FRAP1	0.008	0.004	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.098	0.12	-9999	-0.33	26	26
ErbB2/ErbB2/HSP90 (dimer)	-0.013	0.046	-9999	-0.54	1	1
CHRNA1	-0.092	0.16	-9999	-0.41	58	58
myelination	-0.082	0.16	-9999	-0.36	31	31
PPP3CB	-0.12	0.18	-9999	-0.34	403	403
KRAS	-0.001	0.013	-9999	-0.29	2	2
RAC1-CDC42/GDP	-0.11	0.15	-9999	-0.41	23	23
NRG2	-0.38	0.39	-9999	-0.79	523	523
mol:GDP	-0.12	0.18	-9999	-0.36	403	403
SOS1	0	0	-9999	-10000	0	0
MAP2K2	-0.072	0.15	-9999	-0.44	16	16
SRC	0	0.009	-9999	-0.29	1	1
mol:cAMP	-0.002	0.002	-9999	-10000	0	0
PTPN11	-0.14	0.18	-9999	-0.36	403	403
MAP2K1	-0.13	0.21	-9999	-0.48	171	171
heart morphogenesis	-0.15	0.19	-9999	-0.39	403	403
RAS family/GDP	-0.11	0.14	-9999	-0.4	29	29
GRB2	0	0.009	-9999	-0.3	1	1
PRKACA	-0.01	0.014	-9999	-10000	0	0
CHRNE	0.007	0.023	-9999	-0.18	6	6
HSP90AA1	0	0.009	-9999	-0.29	1	1
activation of caspase activity	-0.008	0.005	-9999	-10000	0	0
nervous system development	-0.15	0.19	-9999	-0.39	403	403
CDC42	0	0	-9999	-10000	0	0

×

EPHB forward signaling

Figure S21. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S21. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.053	0.16	-10000	0	-0.53	104	104
cell-cell adhesion	0.17	0.21	0.67	78	-10000	0	78
Ephrin B/EPHB2/RasGAP	-0.04	0.12	-10000	0	-0.44	96	96
ITSN1	-0.001	0.024	-10000	0	-0.79	1	1
PIK3CA	0	0.009	-10000	0	-0.29	1	1
SHC1	0	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.002	0.018	-10000	0	-10000	0	0
Ephrin B1/EPHB1	-0.21	0.26	-10000	0	-0.53	426	426
HRAS/GDP	-0.17	0.22	-10000	0	-0.64	104	104
Ephrin B/EPHB1/GRB7	-0.22	0.28	-10000	0	-0.52	451	451
Endophilin/SYNJ1	-0.038	0.12	-10000	0	-0.41	96	96
KRAS	-0.001	0.013	-10000	0	-0.29	2	2
Ephrin B/EPHB1/Src	-0.21	0.27	-10000	0	-0.51	449	449
endothelial cell migration	-0.005	0.048	-10000	0	-0.44	13	13
GRB2	0	0.009	-10000	0	-0.29	1	1
GRB7	-0.023	0.085	-10000	0	-0.31	79	79
PAK1	-0.048	0.14	-10000	0	-0.45	107	107
HRAS	-0.002	0.027	-10000	0	-0.29	9	9
RRAS	-0.038	0.12	-10000	0	-0.42	96	96
DNM1	-0.005	0.064	-10000	0	-0.73	8	8
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.2	0.26	-10000	0	-0.48	449	449
lamellipodium assembly	-0.17	0.21	-10000	0	-0.67	78	78
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.15	0.19	-10000	0	-0.36	426	426
PIK3R1	-0.009	0.086	-10000	0	-0.79	13	13
EPHB2	-0.005	0.038	-10000	0	-0.29	19	19
EPHB3	-0.004	0.034	-10000	0	-0.29	15	15
EPHB1	-0.31	0.38	-10000	0	-0.79	426	426
EPHB4	0	0.009	-10000	0	-0.29	1	1
mol:GDP	-0.15	0.21	-10000	0	-0.64	97	97
Ephrin B/EPHB2	-0.041	0.13	-10000	0	-0.45	96	96
Ephrin B/EPHB3	-0.041	0.13	-10000	0	-0.45	96	96
JNK cascade	-0.17	0.21	-10000	0	-0.43	426	426
Ephrin B/EPHB1	-0.21	0.28	-10000	0	-0.52	449	449
RAP1/GDP	-0.13	0.18	-10000	0	-0.6	73	73
EFNB2	0	0	-10000	0	-10000	0	0
EFNB3	-0.069	0.22	-10000	0	-0.79	96	96
EFNB1	0	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.19	0.23	-10000	0	-0.48	426	426
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
CDC42/GTP	-0.18	0.23	-10000	0	-0.75	77	77
Rap1/GTP	-0.17	0.22	-10000	0	-0.7	77	77
axon guidance	-0.053	0.15	-10000	0	-0.52	104	104
MAPK3	-0.096	0.19	-10000	0	-0.52	73	73
MAPK1	-0.096	0.19	-10000	0	-0.52	73	73
Rac1/GDP	-0.14	0.19	-10000	0	-0.57	96	96
actin cytoskeleton reorganization	-0.13	0.16	-10000	0	-0.51	83	83
CDC42/GDP	-0.14	0.19	-10000	0	-0.57	95	95
PI3K	-0.006	0.049	-10000	0	-0.45	13	13
EFNA5	-0.076	0.23	-10000	0	-0.78	105	105
Ephrin B2/EPHB4	0	0.005	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	-0.029	0.094	-10000	0	-0.33	96	96
CDC42	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.16	0.21	-10000	0	-0.66	82	82
PTK2	0.041	0.05	-10000	0	-10000	0	0
MAP4K4	-0.17	0.21	-10000	0	-0.44	426	426
SRC	0	0.009	-10000	0	-0.29	1	1
KALRN	-0.015	0.11	-10000	0	-0.79	21	21
Intersectin/N-WASP	-0.001	0.018	-10000	0	-0.6	1	1
neuron projection morphogenesis	-0.13	0.17	-10000	0	-0.54	83	83
MAP2K1	-0.11	0.2	-10000	0	-0.55	74	74
WASL	0	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.19	0.23	-10000	0	-0.47	426	426
cell migration	-0.12	0.22	-10000	0	-0.62	75	75
NRAS	-0.001	0.013	-10000	0	-0.29	2	2
SYNJ1	-0.038	0.12	-10000	0	-0.42	96	96
PXN	0	0	-10000	0	-10000	0	0
TF	-0.24	0.26	-10000	0	-0.45	624	624
HRAS/GTP	-0.18	0.23	-10000	0	-0.73	81	81
Ephrin B1/EPHB1-2	-0.19	0.23	-10000	0	-0.48	426	426
cell adhesion mediated by integrin	0.009	0.13	0.41	96	-10000	0	96
RAC1	0	0	-10000	0	-10000	0	0
mol:GTP	-0.2	0.25	-10000	0	-0.47	449	449
RAC1-CDC42/GTP	-0.17	0.21	-10000	0	-0.68	78	78
RASA1	0	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.13	0.18	-10000	0	-0.6	73	73
ruffle organization	-0.17	0.22	-10000	0	-0.69	78	78
NCK1	0	0	-10000	0	-10000	0	0
receptor internalization	0.002	0.14	-10000	0	-0.41	98	98
Ephrin B/EPHB2/KALRN	-0.049	0.15	-10000	0	-0.48	107	107
ROCK1	0.022	0.023	-10000	0	-0.48	1	1
RAS family/GDP	-0.12	0.15	-10000	0	-0.52	73	73
Rac1/GTP	-0.18	0.23	-10000	0	-0.74	78	78
Ephrin B/EPHB1/Src/Paxillin	-0.15	0.2	-10000	0	-0.37	449	449

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0	0	-10000	0	-10000	0	0
PTK2	0	0	-10000	0	-10000	0	0
CRKL	-0.1	0.24	-10000	0	-0.48	270	270
GRB2/SOS1/SHC	0	0.004	-10000	0	-10000	0	0
HRAS	-0.002	0.027	-10000	0	-0.29	9	9
IRS1/Crk	-0.12	0.23	-10000	0	-0.48	270	270
IGF-1R heterotetramer/IGF1/PTP1B	-0.13	0.23	-10000	0	-0.53	255	255
AKT1	-0.068	0.21	-10000	0	-0.71	53	53
BAD	-0.055	0.2	-10000	0	-0.66	51	51
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.1	0.24	-10000	0	-0.48	270	270
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.12	0.23	-10000	0	-0.48	270	270
RAF1	-0.048	0.19	-10000	0	-0.63	48	48
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.11	0.22	-10000	0	-0.46	255	255
YWHAZ	-0.001	0.015	-10000	0	-0.29	3	3
IGF-1R heterotetramer/IGF1/IRS1	-0.13	0.24	-10000	0	-0.52	270	270
PIK3CA	0	0.009	-10000	0	-0.29	1	1
RPS6KB1	-0.068	0.21	-10000	0	-0.71	53	53
GNB2L1	0	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.04	0.16	-10000	0	-0.51	48	48
PXN	0	0	-10000	0	-10000	0	0
PIK3R1	-0.009	0.086	-10000	0	-0.79	13	13
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
HRAS/GTP	-0.1	0.19	-10000	0	-0.71	46	46
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.098	0.19	-10000	0	-0.42	255	255
IGF-1R heterotetramer	-0.033	0.13	-10000	0	-0.82	25	25
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.12	0.23	-10000	0	-0.48	270	270
Crk/p130 Cas/Paxillin	-0.11	0.2	-10000	0	-0.44	255	255
IGF1R	-0.033	0.13	-10000	0	-0.82	25	25
IGF1	-0.18	0.34	-10000	0	-0.81	246	246
IRS2/Crk	-0.13	0.25	-10000	0	-0.51	273	273
PI3K	-0.12	0.22	-10000	0	-0.48	257	257
apoptosis	0.08	0.15	0.55	49	-10000	0	49
HRAS/GDP	-0.002	0.018	-10000	0	-10000	0	0
PRKCD	-0.094	0.25	-10000	0	-0.53	255	255
RAF1/14-3-3 E	-0.033	0.16	-10000	0	-0.52	48	48
BAD/14-3-3	-0.044	0.18	-10000	0	-0.6	49	49
PRKCZ	-0.068	0.21	-10000	0	-0.7	54	54
Crk/p130 Cas/Paxillin/FAK1	-0.085	0.16	-10000	0	-0.62	48	48
PTPN1	-0.003	0.029	-10000	0	-0.29	11	11
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.13	0.25	-10000	0	-0.56	255	255
BCAR1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.11	0.2	-10000	0	-0.46	255	255
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.12	0.22	-10000	0	-0.48	270	270
GRB10	0	0	-10000	0	-10000	0	0
PTPN11	-0.1	0.24	-10000	0	-0.48	270	270
IRS1	-0.12	0.25	-10000	0	-0.52	270	270
IRS2	-0.12	0.27	-10000	0	-0.53	284	284
IGF-1R heterotetramer/IGF1	-0.16	0.28	-10000	0	-0.66	255	255
GRB2	0	0.009	-10000	0	-0.29	1	1
PDPK1	-0.11	0.21	-10000	0	-0.45	257	257
YWHAE	0	0	-10000	0	-10000	0	0
PRKD1	-0.11	0.28	-10000	0	-0.56	268	268
SHC1	0	0	-10000	0	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.035	0.049	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.082	0.16	-9999	-0.47	97	97
JUN	-0.05	0.14	-9999	-0.42	63	63
HRAS	-0.002	0.027	-9999	-0.29	9	9
RET51/GFRalpha1/GDNF/GRB10	-0.15	0.2	-9999	-0.52	211	211
RAP1A	0	0	-9999	-10000	0	0
FRS2	-0.003	0.029	-9999	-0.29	11	11
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.15	0.2	-9999	-0.52	211	211
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.1	0.19	-9999	-0.48	207	207
RHOA	0	0	-9999	-10000	0	0
RAP1A/GTP	-0.13	0.18	-9999	-0.46	211	211
GRB7	-0.023	0.085	-9999	-0.31	79	79
RET51/GFRalpha1/GDNF	-0.15	0.2	-9999	-0.52	211	211
MAPKKK cascade	-0.1	0.16	-9999	-0.42	208	208
BCAR1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.12	0.23	-9999	-0.55	219	219
lamellipodium assembly	-0.084	0.15	-9999	-0.36	210	210
RET51/GFRalpha1/GDNF/SHC	-0.15	0.2	-9999	-0.52	211	211
PIK3CA	0	0.009	-9999	-0.29	1	1
RET9/GFRalpha1/GDNF/SHC	-0.1	0.19	-9999	-0.48	207	207
RET9/GFRalpha1/GDNF/Shank3	-0.1	0.19	-9999	-0.48	207	207
MAPK3	-0.12	0.17	-9999	-0.44	208	208
DOK1	-0.001	0.018	-9999	-10000	0	0
DOK6	-0.013	0.095	-9999	-0.63	22	22
PXN	0	0	-9999	-10000	0	0
neurite development	-0.11	0.16	-9999	-0.53	57	57
DOK5	-0.019	0.12	-9999	-0.71	30	30
GFRA1	-0.16	0.31	-9999	-0.68	256	256
MAPK8	-0.077	0.13	-9999	-0.35	149	149
HRAS/GTP	-0.12	0.18	-9999	-0.48	208	208
tube development	-0.095	0.18	-9999	-0.46	202	202
MAPK1	-0.12	0.17	-9999	-0.44	208	208
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.066	0.13	-9999	-0.33	202	202
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0	0.009	-9999	-0.29	1	1
PDLIM7	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.15	0.2	-9999	-0.5	217	217
SHC1	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.15	0.2	-9999	-0.52	211	211
RET51/GFRalpha1/GDNF/Dok5	-0.16	0.22	-9999	-0.54	227	227
PRKCA	-0.021	0.12	-9999	-0.76	30	30
HRAS/GDP	-0.002	0.018	-9999	-10000	0	0
CREB1	-0.074	0.15	-9999	-0.38	202	202
PIK3R1	-0.009	0.086	-9999	-0.79	13	13
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.065	0.13	-9999	-0.33	202	202
RET51/GFRalpha1/GDNF/Grb7	-0.16	0.21	-9999	-0.54	213	213
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.11	0.16	-9999	-0.31	393	393
DOK4	0	0	-9999	-10000	0	0
JNK cascade	-0.049	0.14	-9999	-0.41	63	63
RET9/GFRalpha1/GDNF/FRS2	-0.1	0.19	-9999	-0.49	202	202
SHANK3	0	0	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.066	0.13	-9999	-0.33	202	202
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.083	0.14	-9999	-0.35	208	208
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.083	0.14	-9999	-0.35	208	208
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.084	0.15	-9999	-0.36	208	208
PI3K	-0.14	0.24	-9999	-0.58	215	215
SOS1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.095	0.18	-9999	-0.46	202	202
GRB10	0	0	-9999	-10000	0	0
activation of MAPKK activity	-0.078	0.13	-9999	-0.33	202	202
RET51/GFRalpha1/GDNF/FRS2	-0.15	0.2	-9999	-0.52	211	211
GAB1	0	0	-9999	-10000	0	0
IRS1	-0.033	0.16	-9999	-0.79	45	45
IRS2	-0.033	0.16	-9999	-0.79	45	45
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.084	0.15	-9999	-0.36	208	208
RET51/GFRalpha1/GDNF/PKC alpha	-0.16	0.21	-9999	-0.53	237	237
GRB2	0	0.009	-9999	-0.29	1	1
PRKACA	0	0	-9999	-10000	0	0
GDNF	-0.015	0.065	-9999	-0.29	57	57
RAC1	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.17	0.24	-9999	-0.59	222	222
Rac1/GTP	-0.1	0.18	-9999	-0.44	210	210
RET9/GFRalpha1/GDNF	-0.11	0.21	-9999	-0.53	207	207
GFRalpha1/GDNF	-0.13	0.24	-9999	-0.61	207	207

×

BMP receptor signaling

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
BMP7/BMPR2/BMPR1A-1B/FS	-0.12	0.21	-9999	-0.6	144	144
SMAD6-7/SMURF1	0	0.016	-9999	-0.52	1	1
NOG	-0.025	0.13	-9999	-0.58	47	47
SMAD9	-0.11	0.26	-9999	-0.77	127	127
SMAD4	-0.001	0.024	-9999	-0.79	1	1
SMAD5	-0.075	0.18	-9999	-0.48	140	140
BMP7/USAG1	-0.34	0.34	-9999	-0.66	563	563
SMAD5/SKI	-0.087	0.16	-9999	-0.51	92	92
SMAD1	0.026	0.03	-9999	-10000	0	0
BMP2	-0.14	0.3	-9999	-0.78	193	193
SMAD1/SMAD1/SMAD4	-0.002	0.014	-9999	-10000	0	0
BMPR1A	-0.002	0.041	-9999	-0.79	3	3
BMPR1B	-0.14	0.18	-9999	-0.32	469	469
BMPR1A-1B/BAMBI	-0.092	0.14	-9999	-0.6	60	60
AHSG	-0.005	0.038	-9999	-0.29	19	19
CER1	-0.001	0.015	-9999	-0.29	3	3
BMP2-4/CER1	-0.12	0.24	-9999	-0.57	240	240
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.1	0.2	-9999	-0.51	151	151
BMP2-4 (homodimer)	-0.14	0.28	-9999	-0.64	240	240
RGMB	-0.001	0.024	-9999	-0.79	1	1
BMP6/BMPR2/BMPR1A-1B	-0.097	0.16	-9999	-0.54	109	109
RGMA	-0.11	0.27	-9999	-0.79	146	146
SMURF1	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.11	0.2	-9999	-0.61	109	109
BMP2-4/USAG1	-0.37	0.36	-9999	-0.65	620	620
SMAD6/SMURF1/SMAD5	-0.087	0.16	-9999	-0.51	92	92
SOSTDC1	-0.38	0.39	-9999	-0.79	532	532
BMP7/BMPR2/BMPR1A-1B	-0.11	0.17	-9999	-0.57	115	115
SKI	0	0	-9999	-10000	0	0
BMP6 (homodimer)	-0.06	0.21	-9999	-0.78	84	84
HFE2	-0.003	0.029	-9999	-0.29	11	11
ZFYVE16	0	0	-9999	-10000	0	0
MAP3K7	0	0.009	-9999	-0.29	1	1
BMP2-4/CHRD	-0.14	0.26	-9999	-0.6	244	244
SMAD5/SMAD5/SMAD4	-0.087	0.16	-9999	-0.51	93	93
MAPK1	0	0	-9999	-10000	0	0
TAK1/TAB family	-0.086	0.17	-9999	-0.52	106	106
BMP7 (homodimer)	-0.078	0.22	-9999	-0.64	132	132
NUP214	0	0	-9999	-10000	0	0
BMP6/FETUA	-0.049	0.16	-9999	-0.61	82	82
SMAD1/SKI	0.004	0.018	-9999	-10000	0	0
SMAD6	-0.001	0.024	-9999	-0.79	1	1
CTDSP2	0	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.13	0.24	-9999	-0.57	240	240
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.037	0.12	-9999	-0.36	113	113
BMPR2 (homodimer)	0	0	-9999	-10000	0	0
GADD34/PP1CA	-0.001	0.01	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.092	0.13	-9999	-0.62	29	29
CHRDL1	-0.54	0.37	-9999	-0.79	750	750
ENDOFIN/SMAD1	0.004	0.018	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.003	0.013	-9999	-10000	0	0
SMAD6/SMURF1	0	0	-9999	-10000	0	0
BAMBI	-0.034	0.14	-9999	-0.5	73	73
SMURF2	0	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.47	0.36	-9999	-0.67	768	768
BMP2-4/GREM1	-0.14	0.25	-9999	-0.58	246	246
SMAD7	0	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.1	0.24	-9999	-0.72	127	127
SMAD1/SMAD6	0.004	0.018	-9999	-10000	0	0
TAK1/SMAD6	0	0.006	-9999	-10000	0	0
BMP7	-0.078	0.22	-9999	-0.65	132	132
BMP6	-0.06	0.21	-9999	-0.78	84	84
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.099	0.19	-9999	-0.59	106	106
PPM1A	0	0	-9999	-10000	0	0
SMAD1/SMURF2	0.004	0.018	-9999	-10000	0	0
SMAD7/SMURF1	0	0	-9999	-10000	0	0
CTDSPL	0	0	-9999	-10000	0	0
PPP1CA	-0.001	0.02	-9999	-0.29	5	5
XIAP	0	0	-9999	-10000	0	0
CTDSP1	0	0	-9999	-10000	0	0
PPP1R15A	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.13	0.24	-9999	-0.59	174	174
CHRD	-0.032	0.13	-9999	-0.42	83	83
BMPR2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.13	0.23	-9999	-0.54	200	200
BMP4	-0.051	0.19	-9999	-0.78	71	71
FST	-0.039	0.17	-9999	-0.76	57	57
BMP2-4/NOG	-0.14	0.26	-9999	-0.58	255	255
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.096	0.16	-9999	-0.53	115	115

×

Calcium signaling in the CD4+ TCR 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.01	0.038	-9999	-0.53	3	3
NFATC2	-0.042	0.17	-9999	-0.55	104	104
NFATC3	0.012	0.025	-9999	-10000	0	0
CD40LG	-0.22	0.36	-9999	-0.71	307	307
PTGS2	-0.32	0.46	-9999	-0.85	425	425
JUNB	-0.001	0.013	-9999	-0.29	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.004	0.009	-9999	-10000	0	0
CaM/Ca2+	-0.004	0.009	-9999	-10000	0	0
CALM1	0	0.003	-9999	-10000	0	0
JUN	-0.005	0.064	-9999	-0.8	7	7
mol:Ca2+	-0.007	0.009	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0.005	-9999	-10000	0	0
FOSL1	-0.009	0.06	-9999	-0.35	28	28
CREM	0	0.001	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.077	0.15	-9999	-0.53	79	79
FOS	-0.24	0.37	-9999	-0.8	325	325
IFNG	-0.22	0.35	-9999	-0.68	317	317
AP-1/NFAT1-c-4	-0.31	0.38	-9999	-0.82	316	316
FASLG	-0.21	0.35	-9999	-0.68	302	302
NFAT1-c-4/ICER1	-0.06	0.14	-9999	-0.46	107	107
IL2RA	-0.21	0.35	-9999	-0.69	304	304
FKBP12/FK506	0	0.006	-9999	-10000	0	0
CSF2	-0.2	0.34	-9999	-0.67	300	300
JunB/Fra1/NFAT1-c-4	-0.057	0.14	-9999	-0.48	85	85
IL4	-0.2	0.34	-9999	-0.67	298	298
IL2	-0.009	0.024	-9999	-10000	0	0
IL3	-0.023	0.026	-9999	-10000	0	0
FKBP1A	0	0.009	-9999	-10000	0	0
BATF3	-0.002	0.03	-9999	-0.39	5	5
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.001	0.01	-9999	-0.29	1	1

×

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

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
MET/RANBP9	-0.1	0.23	-10000	0	-0.6	188	188
CRKL	-0.04	0.16	-10000	0	-0.34	188	188
mol:PIP3	-0.018	0.035	0.77	2	-10000	0	2
AKT1	0.003	0.021	0.49	2	-10000	0	2
PTK2B	0	0	-10000	0	-10000	0	0
RAPGEF1	-0.03	0.15	-10000	0	-0.54	21	21
RANBP10	0	0	-10000	0	-10000	0	0
PIK3CA	0	0.009	-10000	0	-0.29	1	1
HGF/MET/SHIP2	-0.12	0.24	-10000	0	-0.56	240	240
MAP3K5	-0.021	0.15	-10000	0	-0.53	25	25
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.11	0.22	-10000	0	-0.51	240	240
AP1	-0.19	0.26	-10000	0	-0.58	326	326
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
apoptosis	-0.23	0.36	-10000	0	-0.78	326	326
STAT3 (dimer)	-0.039	0.16	-10000	0	-0.33	240	240
GAB1/CRKL/SHP2/PI3K	-0.065	0.13	-10000	0	-0.52	34	34
INPP5D	0	0	-10000	0	-10000	0	0
CBL/CRK	-0.032	0.15	-10000	0	-0.54	21	21
PTPN11	0	0	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0	0	-10000	0	-10000	0	0
PTEN	-0.001	0.034	-10000	0	-0.79	2	2
ELK1	-0.044	0.1	-10000	0	-0.27	188	188
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.046	0.092	-10000	0	-0.41	21	21
PAK1	0.008	0.028	0.45	2	-10000	0	2
HGF/MET/RANBP10	-0.12	0.24	-10000	0	-0.56	240	240
HRAS	-0.15	0.3	-10000	0	-0.76	191	191
DOCK1	-0.03	0.15	-10000	0	-0.32	188	188
GAB1	-0.051	0.16	-10000	0	-0.35	240	240
CRK	-0.04	0.16	-10000	0	-0.34	188	188
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.15	0.3	-10000	0	-0.7	240	240
JUN	-0.005	0.063	-10000	0	-0.79	7	7
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.078	0.15	-10000	0	-0.35	240	240
PIK3R1	-0.009	0.086	-10000	0	-0.79	13	13
cell morphogenesis	-0.019	0.18	-10000	0	-0.59	30	30
GRB2/SHC	-0.067	0.13	-10000	0	-0.33	188	188
FOS	-0.24	0.36	-10000	0	-0.79	325	325
GLMN	0	0	-10000	0	-10000	0	0
cell motility	-0.044	0.1	-10000	0	-0.27	188	188
HGF/MET/MUC20	-0.12	0.24	-10000	0	-0.57	240	240
cell migration	-0.066	0.13	-10000	0	-0.32	188	188
GRB2	0	0.009	-10000	0	-0.29	1	1
CBL	0	0	-10000	0	-10000	0	0
MET/RANBP10	-0.1	0.23	-10000	0	-0.6	188	188
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.077	0.15	-10000	0	-0.35	240	240
MET/MUC20	-0.1	0.23	-10000	0	-0.61	188	188
RAP1B	-0.021	0.14	-10000	0	-0.5	21	21
RAP1A	-0.021	0.14	-10000	0	-0.5	21	21
HGF/MET/RANBP9	-0.12	0.24	-10000	0	-0.56	240	240
RAF1	-0.1	0.29	-10000	0	-0.71	188	188
STAT3	-0.073	0.14	-10000	0	-0.33	240	240
cell proliferation	-0.061	0.23	-10000	0	-0.48	240	240
RPS6KB1	-0.027	0.052	-10000	0	-10000	0	0
MAPK3	-0.045	0.092	-10000	0	-0.25	188	188
MAPK1	-0.045	0.092	-10000	0	-0.25	188	188
RANBP9	0	0	-10000	0	-10000	0	0
MAPK8	-0.004	0.14	-10000	0	-0.47	32	32
SRC	-0.071	0.14	-10000	0	-0.61	21	21
PI3K	-0.072	0.14	-10000	0	-0.35	197	197
MET/Glomulin	-0.095	0.21	-10000	0	-0.55	188	188
SOS1	0	0	-10000	0	-10000	0	0
MAP2K1	-0.087	0.27	-10000	0	-0.64	188	188
MET	-0.14	0.3	-10000	0	-0.79	188	188
MAP4K1	-0.03	0.15	-10000	0	-0.32	189	189
PTK2	0	0	-10000	0	-10000	0	0
MAP2K2	-0.087	0.27	-10000	0	-0.64	188	188
BAD	0.011	0.02	0.45	2	-10000	0	2
MAP2K4	-0.011	0.14	-10000	0	-0.47	26	26
SHP2/GRB2/SOS1/GAB1	-0.096	0.19	-10000	0	-0.5	188	188
INPPL1	0	0	-10000	0	-10000	0	0
PXN	0	0	-10000	0	-10000	0	0
SH3KBP1	0	0	-10000	0	-10000	0	0
HGS	-0.071	0.14	-10000	0	-0.35	188	188
PLCgamma1/PKC	0	0	-10000	0	-10000	0	0
HGF	-0.053	0.2	-10000	0	-0.78	75	75
RASA1	0	0	-10000	0	-10000	0	0
NCK1	0	0	-10000	0	-10000	0	0
PTPRJ	0	0	-10000	0	-10000	0	0
NCK/PLCgamma1	-0.067	0.13	-10000	0	-0.32	188	188
PDPK1	-0.006	0.025	0.56	2	-10000	0	2
HGF/MET/SHIP	-0.12	0.24	-10000	0	-0.56	240	240

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.011	0.001	-10000	0	-10000	0	0
GNB1/GNG2	-0.07	0.17	-10000	0	-0.48	158	158
regulation of S phase of mitotic cell cycle	-0.044	0.12	-10000	0	-0.34	151	151
GNAO1	-0.03	0.13	-10000	0	-0.49	67	67
HRAS	-0.002	0.027	-10000	0	-0.3	9	9
SHBG/T-DHT	0	0	-10000	0	-10000	0	0
PELP1	0	0	-10000	0	-10000	0	0
AKT1	0.011	0.001	-10000	0	-10000	0	0
MAP2K1	-0.045	0.16	-10000	0	-0.42	146	146
T-DHT/AR	-0.082	0.21	-10000	0	-0.61	146	146
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.002	0.004	-10000	0	-0.007	323	323
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.045	0.18	-10000	0	-0.79	62	62
mol:GDP	-0.084	0.21	-10000	0	-0.62	146	146
cell proliferation	-0.1	0.24	-10000	0	-0.56	110	110
PIK3CA	0	0.009	-10000	0	-0.29	1	1
FOS	-0.23	0.42	-10000	0	-0.86	325	325
mol:Ca2+	-0.017	0.028	-10000	0	-0.076	149	149
MAPK3	-0.076	0.2	-10000	0	-0.6	65	65
MAPK1	-0.047	0.12	-10000	0	-0.3	62	62
PIK3R1	-0.009	0.086	-10000	0	-0.79	13	13
mol:IP3	-0.001	0.002	-10000	0	-0.005	325	325
cAMP biosynthetic process	0.013	0.025	-10000	0	-10000	0	0
GNG2	-0.009	0.086	-10000	0	-0.79	13	13
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.005	325	325
HRAS/GTP	-0.068	0.15	-10000	0	-0.45	146	146
actin cytoskeleton reorganization	-0.005	0.046	-10000	0	-0.42	13	13
SRC	0	0.009	-10000	0	-0.29	1	1
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.005	325	325
PI3K	-0.006	0.057	-10000	0	-0.53	13	13
apoptosis	0.11	0.23	0.43	325	-10000	0	325
T-DHT/AR/PELP1	-0.071	0.18	-10000	0	-0.53	146	146
HRAS/GDP	-0.08	0.2	-10000	0	-0.59	147	147
CREB1	-0.12	0.24	-10000	0	-0.46	325	325
RAC1-CDC42/GTP	-0.005	0.047	-10000	0	-0.43	13	13
AR	-0.11	0.27	-10000	0	-0.79	147	147
GNB1	0	0	-10000	0	-10000	0	0
RAF1	-0.045	0.16	-10000	0	-0.44	146	146
RAC1-CDC42/GDP	-0.075	0.19	-10000	0	-0.56	146	146
T-DHT/AR/PELP1/Src	-0.065	0.17	-10000	0	-0.49	146	146
MAP2K2	-0.045	0.16	-10000	0	-0.42	146	146
T-DHT/AR/PELP1/Src/PI3K	-0.044	0.12	-10000	0	-0.35	151	151
GNAZ	-0.007	0.071	-10000	0	-0.79	9	9
SHBG	0	0	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.039	0.11	-10000	0	-0.49	39	39
mol:T-DHT	-0.001	0.001	0.002	9	-0.003	261	270
RAC1	0	0	-10000	0	-10000	0	0
GNRH1	0.006	0.056	-10000	0	-0.61	9	9
Gi family/GTP	-0.051	0.1	-10000	0	-0.3	97	97
CDC42	0	0	-10000	0	-10000	0	0

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.027	0.062	-10000	0	-0.49	2	2
epithelial cell differentiation	-0.021	0.065	-10000	0	-0.53	6	6
ITCH	0.01	0.022	-10000	0	-10000	0	0
WWP1	0.007	0.068	-10000	0	-10000	0	0
FYN	-0.001	0.034	-10000	0	-0.79	2	2
EGFR	-0.3	0.38	-10000	0	-0.78	414	414
PRL	-0.004	0.033	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.1	0.21	-10000	0	-0.46	72	72
PTPRZ1	-0.41	0.39	-10000	0	-0.78	573	573
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.16	0.2	-10000	0	-0.52	76	76
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.19	0.23	-10000	0	-0.49	401	401
ADAM17	0.01	0.022	-10000	0	-10000	0	0
ErbB4/ErbB4	0	0.086	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.056	0.13	-10000	0	-0.53	59	59
NCOR1	-0.001	0.024	-10000	0	-0.79	1	1
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.18	0.22	-10000	0	-0.46	401	401
GRIN2B	-0.17	0.25	-10000	0	-0.46	451	451
ErbB4/ErbB2/betacellulin	-0.05	0.11	-10000	0	-0.47	62	62
STAT1	-0.005	0.038	-10000	0	-0.29	19	19
HBEGF	-0.001	0.034	-10000	0	-0.79	2	2
PRLR	-0.008	0.071	-10000	0	-0.79	8	8
E4ICDs/ETO2	-0.035	0.09	-10000	0	-0.55	19	19
axon guidance	0.043	0.12	-10000	0	-0.43	3	3
NEDD4	0.01	0.022	-10000	0	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	-0.008	0.058	-10000	0	-0.61	8	8
CBFA2T3	-0.015	0.1	-10000	0	-0.69	24	24
ErbB4/ErbB2/HBEGF	-0.026	0.054	-10000	0	-0.48	3	3
MAPK3	-0.15	0.18	-10000	0	-0.48	76	76
STAT1 (dimer)	-0.028	0.063	-10000	0	-10000	0	0
MAPK1	-0.15	0.18	-10000	0	-0.48	76	76
JAK2	-0.001	0.024	-10000	0	-0.79	1	1
ErbB4/ErbB2/neuregulin 1 beta	-0.19	0.22	-10000	0	-0.47	401	401
NRG1	-0.21	0.3	-10000	0	-0.61	401	401
NRG3	-0.05	0.18	-10000	0	-0.79	59	59
NRG2	-0.38	0.39	-10000	0	-0.79	523	523
NRG4	-0.005	0.038	-10000	0	-0.29	19	19
heart development	0.043	0.12	-10000	0	-0.43	3	3
neural crest cell migration	-0.19	0.22	-10000	0	-0.46	401	401
ERBB2	0.009	0.062	-10000	0	-0.6	1	1
WWOX/E4ICDs	-0.026	0.059	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.19	0.21	-10000	0	-0.46	409	409
apoptosis	0.057	0.14	0.54	59	-10000	0	59
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.26	0.24	-10000	0	-0.5	523	523
ErbB4/ErbB2/epiregulin	-0.084	0.15	-10000	0	-0.46	129	129
ErbB4/ErbB4/betacellulin/betacellulin	-0.054	0.12	-10000	0	-0.51	61	61
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.025	0.067	-10000	0	-0.56	8	8
MDM2	0.008	0.075	-10000	0	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.18	0.22	-10000	0	-0.47	401	401
STAT5A	0.043	0.12	-10000	0	-0.47	7	7
ErbB4/EGFR/neuregulin 1 beta	-0.34	0.35	-10000	0	-0.65	560	560
DLG4	0	0	-10000	0	-10000	0	0
GRB2/SHC	0	0.006	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.024	0.055	-10000	0	-0.46	1	1
STAT5A (dimer)	-0.022	0.07	-10000	0	-0.6	5	5
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.025	0.11	-10000	0	-0.43	5	5
LRIG1	-0.002	0.041	-10000	0	-0.79	3	3
EREG	-0.11	0.26	-10000	0	-0.6	207	207
BTC	-0.045	0.18	-10000	0	-0.77	64	64
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.043	0.12	-10000	0	-0.43	3	3
ERBB4	-0.032	0.072	-10000	0	-10000	0	0
STAT5B	-0.002	0.041	-10000	0	-0.79	3	3
YAP1	-0.01	0.043	-10000	0	-0.64	4	4
GRB2	0	0.009	-10000	0	-0.29	1	1
ErbB4/ErbB2/neuregulin 4	-0.027	0.055	-10000	0	-0.57	1	1
glial cell differentiation	0.024	0.055	0.45	1	-10000	0	1
WWOX	-0.001	0.013	-10000	0	-0.29	2	2
cell proliferation	-0.12	0.24	-10000	0	-0.58	75	75

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.001	0.015	-9999	-0.29	3	3
CCL5	-0.015	0.079	-9999	-0.36	44	44
SDCBP	0	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.08	0.11	-9999	-0.34	108	108
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.075	0.097	-9999	-0.35	49	49
Syndecan-1/Syntenin	-0.075	0.097	-9999	-0.35	48	48
MAPK3	-0.048	0.096	-9999	-0.48	5	5
HGF/MET	-0.14	0.28	-9999	-0.64	240	240
TGFB1/TGF beta receptor Type II	-0.001	0.015	-9999	-0.29	3	3
BSG	0	0.009	-9999	-10000	0	0
keratinocyte migration	-0.074	0.095	-9999	-0.35	49	49
Syndecan-1/RANTES	-0.082	0.11	-9999	-0.34	110	110
Syndecan-1/CD147	-0.066	0.094	-9999	-0.49	6	6
Syndecan-1/Syntenin/PIP2	-0.072	0.093	-9999	-0.34	48	48
LAMA5	0	0.009	-9999	-0.29	1	1
positive regulation of cell-cell adhesion	-0.071	0.092	-9999	-0.33	48	48
MMP7	-0.12	0.28	-9999	-0.71	191	191
HGF	-0.053	0.2	-9999	-0.78	75	75
Syndecan-1/CASK	-0.077	0.1	-9999	-0.33	108	108
Syndecan-1/HGF/MET	-0.17	0.25	-9999	-0.58	243	243
regulation of cell adhesion	-0.039	0.094	-9999	-0.48	4	4
HPSE	-0.006	0.05	-9999	-0.34	20	20
positive regulation of cell migration	-0.08	0.11	-9999	-0.34	108	108
SDC1	-0.081	0.11	-9999	-0.35	108	108
Syndecan-1/Collagen	-0.08	0.11	-9999	-0.34	108	108
PPIB	-0.001	0.015	-9999	-0.29	3	3
MET	-0.14	0.3	-9999	-0.79	188	188
PRKACA	0	0	-9999	-10000	0	0
MMP9	-0.13	0.15	-9999	-0.29	484	484
MAPK1	-0.048	0.096	-9999	-0.48	5	5
homophilic cell adhesion	-0.08	0.11	-9999	-0.34	108	108
MMP1	-0.22	0.13	-9999	-0.29	824	824

×

Noncanonical Wnt signaling pathway

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
NFATC2	-0.075	0.23	-9999	-0.79	104	104
GNB1/GNG2	-0.14	0.23	-9999	-0.68	111	111
mol:DAG	-0.094	0.22	-9999	-0.6	111	111
PLCG1	-0.13	0.21	-9999	-0.63	111	111
YES1	-0.14	0.23	-9999	-0.66	117	117
FZD3	-0.011	0.092	-9999	-0.79	15	15
FZD6	-0.007	0.075	-9999	-0.79	10	10
G protein	-0.13	0.21	-9999	-0.64	113	113
MAP3K7	-0.067	0.18	-9999	-0.49	109	109
mol:Ca2+	-0.09	0.21	-9999	-0.58	111	111
mol:IP3	-0.094	0.22	-9999	-0.6	111	111
NLK	-0.005	0.01	-9999	-10000	0	0
GNB1	0	0	-9999	-10000	0	0
CAMK2A	-0.081	0.2	-9999	-0.53	115	115
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.16	0.24	-9999	-0.44	381	381
CSNK1A1	0	0	-9999	-10000	0	0
GNAS	-0.14	0.23	-9999	-0.66	118	118
GO:0007205	-0.091	0.22	-9999	-0.59	111	111
WNT6	-0.16	0.31	-9999	-0.69	255	255
WNT4	-0.022	0.12	-9999	-0.55	43	43
NFAT1/CK1 alpha	-0.16	0.23	-9999	-0.63	143	143
GNG2	-0.009	0.086	-9999	-0.79	13	13
WNT5A	-0.016	0.1	-9999	-0.61	28	28
WNT11	-0.16	0.32	-9999	-0.76	235	235
CDC42	-0.1	0.23	-9999	-0.66	102	102

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.096	0.18	-10000	0	-0.46	197	197
ER alpha/Gai/GDP/Gbeta gamma	-0.093	0.19	-10000	0	-0.47	191	191
AKT1	-0.1	0.32	-10000	0	-0.83	172	172
PIK3CA	0	0.009	-10000	0	-0.29	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.11	0.32	-10000	0	-0.85	169	169
mol:Ca2+	-0.029	0.15	-10000	0	-0.45	93	93
IGF1R	-0.02	0.12	-10000	0	-0.79	22	22
E2/ER alpha (dimer)/Striatin	-0.11	0.2	-10000	0	-0.53	184	184
SHC1	0	0	-10000	0	-10000	0	0
apoptosis	0.095	0.3	0.79	172	-10000	0	172
RhoA/GTP	-0.07	0.14	-10000	0	-0.39	167	167
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.094	0.2	-10000	0	-0.53	177	177
regulation of stress fiber formation	0.024	0.14	0.45	11	-10000	0	11
E2/ERA-ERB (dimer)	-0.11	0.2	-10000	0	-0.54	188	188
KRAS	-0.001	0.013	-10000	0	-0.29	2	2
G13/GTP	-0.09	0.17	-10000	0	-0.48	167	167
pseudopodium formation	-0.024	0.14	-10000	0	-0.45	11	11
E2/ER alpha (dimer)/PELP1	-0.098	0.19	-10000	0	-0.53	167	167
GRB2	0	0.009	-10000	0	-0.29	1	1
GNG2	-0.009	0.086	-10000	0	-0.79	13	13
GNAO1	-0.03	0.13	-10000	0	-0.49	67	67
HRAS	-0.002	0.027	-10000	0	-0.29	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.062	0.22	-10000	0	-0.54	180	180
E2/ER beta (dimer)	-0.013	0.088	-10000	0	-0.61	23	23
mol:GDP	-0.087	0.2	-10000	0	-0.53	188	188
mol:NADP	-0.062	0.22	-10000	0	-0.54	180	180
PIK3R1	-0.009	0.086	-10000	0	-0.79	13	13
mol:IP3	-0.031	0.16	-10000	0	-0.47	93	93
IGF-1R heterotetramer	-0.02	0.12	-10000	0	-0.79	22	22
PLCB1	-0.065	0.15	-10000	0	-0.49	92	92
PLCB2	-0.034	0.092	-10000	0	-0.65	15	15
IGF1	-0.18	0.33	-10000	0	-0.79	246	246
mol:L-citrulline	-0.062	0.22	-10000	0	-0.54	180	180
RHOA	0	0	-10000	0	-10000	0	0
Gai/GDP	-0.04	0.15	-10000	0	-0.85	26	26
JNK cascade	-0.013	0.087	-10000	0	-0.61	23	23
BCAR1	0	0	-10000	0	-10000	0	0
ESR2	-0.017	0.11	-10000	0	-0.79	23	23
GNAQ	-0.002	0.041	-10000	0	-0.79	3	3
ESR1	-0.15	0.28	-10000	0	-0.58	291	291
Gq family/GDP/Gbeta gamma	-0.008	0.074	-10000	0	-0.7	8	8
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.024	0.13	-10000	0	-0.35	17	17
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.094	0.2	-10000	0	-0.53	177	177
GNAZ	-0.007	0.071	-10000	0	-0.79	9	9
E2/ER alpha (dimer)	-0.12	0.22	-10000	0	-0.61	167	167
STRN	-0.014	0.11	-10000	0	-0.79	20	20
GNAL	-0.19	0.34	-10000	0	-0.79	259	259
PELP1	0	0	-10000	0	-10000	0	0
MAPK11	0.005	0.083	-10000	0	-0.52	26	26
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.045	0.18	-10000	0	-0.79	62	62
HBEGF	-0.072	0.19	-10000	0	-0.45	188	188
cAMP biosynthetic process	-0.19	0.26	-10000	0	-0.51	389	389
SRC	-0.052	0.2	-10000	0	-0.44	179	179
PI3K	-0.007	0.066	-10000	0	-0.6	13	13
GNB1	0	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.079	0.18	-10000	0	-0.46	197	197
SOS1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.15	0.23	-10000	0	-0.53	222	222
Gs family/GTP	-0.19	0.26	-10000	0	-0.52	389	389
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.002	0.014	-10000	0	-10000	0	0
vasodilation	-0.058	0.21	-10000	0	-0.51	180	180
mol:DAG	-0.031	0.16	-10000	0	-0.47	93	93
Gs family/GDP/Gbeta gamma	-0.16	0.23	-10000	0	-0.44	391	391
MSN	-0.027	0.15	-10000	0	-0.5	11	11
Gq family/GTP	-0.038	0.097	-10000	0	-0.69	14	14
mol:PI-3-4-5-P3	-0.1	0.31	-10000	0	-0.81	169	169
NRAS	-0.001	0.013	-10000	0	-0.29	2	2
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.058	0.21	0.51	180	-10000	0	180
GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
RhoA/GDP	-0.08	0.19	-10000	0	-0.49	188	188
NOS3	-0.067	0.24	-10000	0	-0.57	180	180
GNA11	-0.002	0.041	-10000	0	-0.79	3	3
MAPKKK cascade	-0.069	0.26	-10000	0	-0.63	184	184
E2/ER alpha (dimer)/PELP1/Src	-0.098	0.22	-10000	0	-0.56	177	177
ruffle organization	-0.024	0.14	-10000	0	-0.45	11	11
ROCK2	-0.075	0.14	-10000	0	-0.37	195	195
GNA14	-0.013	0.085	-10000	0	-0.45	32	32
GNA15	-0.003	0.033	-10000	0	-0.36	8	8
GNA13	0	0	-10000	0	-10000	0	0
MMP9	-0.098	0.2	-10000	0	-0.48	188	188
MMP2	-0.045	0.19	-10000	0	-0.43	184	184

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.22	0.26	-10000	0	-0.53	450	450
fibroblast growth factor receptor signaling pathway	-0.22	0.26	-10000	0	-0.52	450	450
LAMA1	-0.09	0.25	-10000	0	-0.77	127	127
PRNP	-0.012	0.098	-10000	0	-0.79	17	17
GPC1/SLIT2	-0.07	0.19	-10000	0	-0.6	126	126
SMAD2	0.01	0.1	-10000	0	-0.47	49	49
GPC1/PrPc/Cu2+	-0.01	0.068	-10000	0	-0.53	18	18
GPC1/Laminin alpha1	-0.07	0.19	-10000	0	-0.6	124	124
TDGF1	-0.008	0.076	-10000	0	-0.79	10	10
CRIPTO/GPC1	-0.007	0.062	-10000	0	-0.6	11	11
APP/GPC1	-0.002	0.023	-10000	0	-0.6	1	1
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0.019	0.058	-10000	0	-0.52	12	12
FLT1	-0.001	0.024	-10000	0	-0.79	1	1
GPC1/TGFB/TGFBR1/TGFBR2	-0.024	0.11	-10000	0	-0.52	49	49
SERPINC1	-0.018	0.07	-10000	0	-10000	0	0
FYN	0.018	0.06	-10000	0	-0.52	13	13
FGR	0.019	0.058	-10000	0	-0.52	12	12
positive regulation of MAPKKK cascade	0.03	0.072	-10000	0	-0.52	13	13
SLIT2	-0.09	0.25	-10000	0	-0.79	125	125
GPC1/NRG	-0.22	0.29	-10000	0	-0.6	402	402
NRG1	-0.29	0.38	-10000	0	-0.78	406	406
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.003	0.029	-10000	0	-0.52	2	2
LYN	0.019	0.056	-10000	0	-0.52	11	11
mol:Spermine	0.009	0.024	-10000	0	-0.61	1	1
cell growth	-0.22	0.26	-10000	0	-0.52	450	450
BMP signaling pathway	0.002	0.032	0.79	1	-10000	0	1
SRC	0.019	0.056	-10000	0	-0.52	11	11
TGFBR1	0	0.009	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.26	0.37	-10000	0	-0.75	379	379
GPC1	-0.002	0.032	-10000	0	-0.79	1	1
TGFBR1 (dimer)	0	0.009	-10000	0	-10000	0	0
VEGFA	-0.003	0.031	-10000	0	-0.29	12	12
BLK	-0.008	0.086	-10000	0	-0.55	13	13
HCK	0.017	0.059	-10000	0	-0.52	11	11
FGF2	-0.32	0.39	-10000	0	-0.79	444	444
FGFR1	-0.009	0.08	-10000	0	-0.68	14	14
VEGFR1 homodimer	-0.001	0.024	-10000	0	-0.79	1	1
TGFBR2	-0.035	0.16	-10000	0	-0.79	48	48
cell death	-0.002	0.023	-10000	0	-0.6	1	1
ATIII/GPC1	-0.013	0.05	-10000	0	-0.61	1	1
PLA2G2A/GPC1	-0.2	0.28	-10000	0	-0.6	352	352
LCK	0.006	0.087	-10000	0	-0.53	24	24
neuron differentiation	-0.22	0.29	-10000	0	-0.6	402	402
PrPc/Cu2+	-0.01	0.076	-10000	0	-0.61	17	17
APP	0	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	-0.035	0.16	-10000	0	-0.79	48	48

×

Neurotrophic factor-mediated Trk receptor 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
CRKL	0	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.1	0.12	-10000	0	-0.33	84	84
NT3 (dimer)/TRKC	-0.29	0.36	-10000	0	-0.68	462	462
NT3 (dimer)/TRKB	-0.5	0.44	-10000	0	-0.78	696	696
SHC/Grb2/SOS1/GAB1/PI3K	-0.004	0.035	-10000	0	-0.32	13	13
RAPGEF1	0	0	-10000	0	-10000	0	0
BDNF	-0.065	0.21	-10000	0	-0.67	106	106
PIK3CA	0	0.009	-10000	0	-0.29	1	1
DYNLT1	0	0.009	-10000	0	-0.29	1	1
NTRK1	-0.011	0.07	-10000	0	-0.37	33	33
NTRK2	-0.42	0.39	-10000	0	-0.79	574	574
NTRK3	-0.27	0.37	-10000	0	-0.78	376	376
NT-4/5 (dimer)/TRKB	-0.58	0.48	-10000	0	-0.85	746	746
neuron apoptosis	0.24	0.24	0.58	301	-10000	0	301
SHC 2-3/Grb2	-0.26	0.28	-10000	0	-0.66	301	301
SHC1	0	0	-10000	0	-10000	0	0
SHC2	-0.25	0.29	-10000	0	-0.6	353	353
SHC3	-0.24	0.28	-10000	0	-0.66	290	290
STAT3 (dimer)	-0.005	0.03	-10000	0	-0.38	4	4
NT3 (dimer)/TRKA	-0.24	0.32	-10000	0	-0.6	434	434
RIN/GDP	-0.065	0.12	-10000	0	-0.28	66	66
GIPC1	-0.001	0.015	-10000	0	-0.29	3	3
KRAS	-0.001	0.013	-10000	0	-0.29	2	2
DNAJA3	-0.14	0.2	-10000	0	-0.43	344	344
RIN/GTP	-0.001	0.01	-10000	0	-10000	0	0
CCND1	0.017	0.075	-10000	0	-1	4	4
MAGED1	-0.001	0.018	-10000	0	-0.29	4	4
PTPN11	0	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.27	0.37	-10000	0	-0.79	372	372
SHC/GRB2/SOS1	0	0.004	-10000	0	-10000	0	0
GRB2	0	0.009	-10000	0	-0.29	1	1
NGF (dimer)/TRKA/MATK	-0.028	0.11	-10000	0	-0.55	38	38
TRKA/NEDD4-2	-0.008	0.053	-10000	0	-0.6	6	6
ELMO1	0	0	-10000	0	-10000	0	0
RhoG/GTP/ELMO1/DOCK1	0	0	-10000	0	-10000	0	0
NGF	-0.014	0.098	-10000	0	-0.62	24	24
HRAS	-0.002	0.027	-10000	0	-0.29	9	9
DOCK1	0	0	-10000	0	-10000	0	0
GAB2	-0.004	0.043	-10000	0	-0.79	2	2
RIT2	-0.001	0.015	-10000	0	-0.29	3	3
RIT1	0	0	-10000	0	-10000	0	0
FRS2	-0.003	0.029	-10000	0	-0.29	11	11
DNM1	-0.005	0.064	-10000	0	-0.73	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.13	0.2	-10000	0	-0.42	336	336
mol:GDP	-0.1	0.18	-10000	0	-0.36	234	234
NGF (dimer)	-0.014	0.098	-10000	0	-0.62	24	24
RhoG/GDP	0	0	-10000	0	-10000	0	0
RIT1/GDP	-0.061	0.12	-10000	0	-0.27	67	67
TIAM1	-0.001	0.018	-10000	0	-0.29	4	4
PIK3R1	-0.009	0.086	-10000	0	-0.79	13	13
BDNF (dimer)/TRKB	-0.31	0.3	-10000	0	-0.56	599	599
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2	-0.001	0.014	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0	0.004	-10000	0	-10000	0	0
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.13	0.28	-10000	0	-0.75	182	182
RAP1/GDP	-0.072	0.084	-10000	0	-0.24	39	39
KIDINS220/CRKL	0	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.065	0.21	-10000	0	-0.67	106	106
ubiquitin-dependent protein catabolic process	-0.015	0.076	-10000	0	-0.52	22	22
Schwann cell development	-0.059	0.044	-10000	0	-10000	0	0
EHD4	0	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	-0.001	0.012	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	-0.001	0.011	-10000	0	-10000	0	0
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
CDC42/GTP	-0.42	0.38	-10000	0	-0.85	404	404
ABL1	0	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
Rap1/GTP	-0.1	0.097	-10000	0	-10000	0	0
STAT3	-0.005	0.03	-10000	0	-0.38	4	4
axon guidance	-0.4	0.34	-10000	0	-0.77	422	422
MAPK3	0.006	0.1	-10000	0	-0.5	38	38
MAPK1	0.006	0.1	-10000	0	-0.5	38	38
CDC42/GDP	-0.061	0.12	-10000	0	-0.28	61	61
NTF3	-0.13	0.29	-10000	0	-0.75	182	182
NTF4	-0.27	0.37	-10000	0	-0.79	372	372
NGF (dimer)/TRKA/FAIM	-0.015	0.075	-10000	0	-0.52	21	21
PI3K	-0.007	0.066	-10000	0	-0.6	13	13
FRS3	0	0	-10000	0	-10000	0	0
FAIM	0	0	-10000	0	-10000	0	0
GAB1	0	0	-10000	0	-10000	0	0
RASGRF1	-0.15	0.21	-10000	0	-0.45	347	347
SOS1	0	0	-10000	0	-10000	0	0
MCF2L	-0.24	0.33	-10000	0	-0.6	464	464
RGS19	-0.001	0.015	-10000	0	-0.29	3	3
CDC42	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.001	0.082	-10000	0	-10000	0	0
Rac1/GDP	-0.061	0.12	-10000	0	-0.27	67	67
NGF (dimer)/TRKA/GRIT	-0.015	0.077	-10000	0	-0.53	21	21
neuron projection morphogenesis	-0.1	0.21	-10000	0	-0.63	27	27
NGF (dimer)/TRKA/NEDD4-2	-0.015	0.077	-10000	0	-0.52	22	22
MAP2K1	0	0.003	-10000	0	-10000	0	0
NGFR	-0.24	0.36	-10000	0	-0.79	336	336
NGF (dimer)/TRKA/GIPC/GAIP	-0.01	0.053	-10000	0	-0.33	27	27
RAS family/GTP/PI3K	-0.004	0.036	-10000	0	-0.33	13	13
FRS2 family/SHP2/GRB2/SOS1	-0.001	0.011	-10000	0	-10000	0	0
NRAS	-0.001	0.013	-10000	0	-0.29	2	2
GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
PRKCI	0	0.009	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
PRKCZ	-0.001	0.024	-10000	0	-0.79	1	1
MAPKKK cascade	-0.064	0.12	-10000	0	-0.82	21	21
RASA1	0	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.008	0.05	-10000	0	-0.6	5	5
SQSTM1	0	0.009	-10000	0	-0.29	1	1
BDNF (dimer)/TRKB/GIPC	-0.28	0.27	-10000	0	-0.52	599	599
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.012	0.064	-10000	0	-0.44	22	22
MATK	-0.022	0.11	-10000	0	-0.79	19	19
NEDD4L	-0.001	0.024	-10000	0	-0.79	1	1
RAS family/GDP	-0.065	0.078	-10000	0	-0.24	1	1
NGF (dimer)/TRKA	-0.15	0.22	-10000	0	-0.46	344	344
Rac1/GTP	-0.12	0.14	-10000	0	-0.34	262	262
FRS2 family/SHP2/CRK family	-0.001	0.01	-10000	0	-10000	0	0

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.003	0.048	-10000	0	-0.79	4	4
Jak2/Leptin Receptor	-0.16	0.23	-10000	0	-0.52	302	302
PTP1B/AKT1	-0.07	0.11	-10000	0	-0.34	116	116
FYN	-0.001	0.034	-10000	0	-0.79	2	2
p210 bcr-abl/PTP1B	-0.071	0.13	-10000	0	-0.35	146	146
EGFR	-0.3	0.39	-10000	0	-0.79	414	414
EGF/EGFR	-0.29	0.3	-10000	0	-0.56	557	557
CSF1	-0.005	0.063	-10000	0	-0.79	7	7
AKT1	0.001	0.004	-10000	0	-10000	0	0
INSR	0.001	0.01	-10000	0	-0.3	1	1
PTP1B/N-cadherin	-0.097	0.12	-10000	0	-0.35	139	139
Insulin Receptor/Insulin	-0.049	0.08	-10000	0	-0.4	21	21
HCK	-0.004	0.033	-10000	0	-10000	0	0
CRK	0	0	-10000	0	-10000	0	0
TYK2	-0.06	0.12	-10000	0	-0.36	116	116
EGF	-0.15	0.32	-10000	0	-0.8	215	215
YES1	-0.001	0.024	-10000	0	-0.79	1	1
CAV1	-0.18	0.24	-10000	0	-0.5	302	302
TXN	0	0.018	-10000	0	-0.3	4	4
PTP1B/IRS1/GRB2	-0.087	0.14	-10000	0	-0.4	151	151
cell migration	0.071	0.13	0.35	146	-10000	0	146
STAT3	0	0.001	-10000	0	-10000	0	0
PRLR	-0.006	0.072	-10000	0	-0.79	8	8
ITGA2B	-0.018	0.079	-10000	0	-0.32	64	64
CSF1R	-0.001	0.025	-10000	0	-0.54	2	2
Prolactin Receptor/Prolactin	-0.007	0.058	-10000	0	-0.61	8	8
FGR	-0.001	0.025	-10000	0	-0.54	2	2
PTP1B/p130 Cas	-0.074	0.11	-10000	0	-0.36	116	116
Crk/p130 Cas	-0.069	0.11	-10000	0	-0.35	112	112
DOK1	-0.046	0.11	-10000	0	-0.32	108	108
JAK2	-0.042	0.081	-10000	0	-0.33	30	30
Jak2/Leptin Receptor/Leptin	-0.36	0.19	-10000	0	-0.49	558	558
PIK3R1	-0.009	0.086	-10000	0	-0.79	13	13
PTPN1	-0.072	0.13	-10000	0	-0.35	146	146
LYN	0	0	-10000	0	-10000	0	0
CDH2	-0.055	0.12	-10000	0	-0.3	200	200
SRC	-0.013	0.047	-10000	0	-10000	0	0
ITGB3	-0.028	0.15	-10000	0	-0.74	42	42
CAT1/PTP1B	-0.084	0.17	-10000	0	-0.38	185	185
CAPN1	0.001	0.01	-10000	0	-0.3	1	1
CSK	0	0	-10000	0	-10000	0	0
PI3K	-0.044	0.093	-10000	0	-0.53	20	20
mol:H2O2	-0.005	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	-0.32	0.16	-10000	0	-0.43	543	543
negative regulation of transcription	-0.041	0.08	-10000	0	-0.32	30	30
FCGR2A	-0.001	0.013	-10000	0	-0.29	2	2
FER	-0.007	0.08	-10000	0	-0.8	11	11
alphaIIb/beta3 Integrin	-0.034	0.12	-10000	0	-0.62	41	41
BLK	-0.044	0.11	-10000	0	-0.3	159	159
Insulin Receptor/Insulin/Shc	0	0.005	-10000	0	-10000	0	0
RHOA	0.002	0.004	-10000	0	-10000	0	0
LEPR	-0.21	0.36	-10000	0	-0.79	294	294
BCAR1	0	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0	0.009	-10000	0	-0.29	1	1
mol:NADPH	-0.005	0.005	-10000	0	-10000	0	0
TRPV6	-0.031	0.13	-10000	0	-0.44	22	22
PRL	-0.004	0.034	-10000	0	-0.31	2	2
SOCS3	0.018	0.11	-10000	0	-1.5	6	6
SPRY2	-0.093	0.26	-10000	0	-0.8	127	127
Insulin Receptor/Insulin/IRS1	-0.022	0.11	-10000	0	-0.53	45	45
CSF1/CSF1R	-0.072	0.12	-10000	0	-0.36	121	121
Ras protein signal transduction	0.037	0.036	-10000	0	-10000	0	0
IRS1	-0.033	0.16	-10000	0	-0.79	45	45
INS	0	0.001	-10000	0	-10000	0	0
LEP	-0.62	0.32	-10000	0	-0.79	861	861
STAT5B	-0.058	0.11	-10000	0	-0.31	123	123
STAT5A	-0.059	0.11	-10000	0	-0.31	126	126
GRB2	0	0.009	-10000	0	-0.29	1	1
PDGFB-D/PDGFRB	-0.076	0.12	-10000	0	-0.37	118	118
CSN2	0.018	0.035	-10000	0	-10000	0	0
PIK3CA	0	0.009	-10000	0	-0.29	1	1
LAT	-0.014	0.053	-10000	0	-0.57	2	2
YBX1	-0.001	0.014	-10000	0	-10000	0	0
LCK	-0.02	0.1	-10000	0	-0.41	54	54
SHC1	0	0	-10000	0	-10000	0	0
NOX4	-0.004	0.05	-10000	0	-0.41	13	13

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.076	0.068	-9999	-0.61	1	1
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.02	0.018	-9999	-10000	0	0
AURKB	-0.17	0.14	-9999	-0.29	625	625
AURKC	-0.005	0.043	-9999	-0.32	18	18

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	-0.005	0.045	-9999	-0.6	5	5
alphaV beta3 Integrin	-0.23	0.28	-9999	-0.54	458	458
PTK2	-0.089	0.19	-9999	-0.64	49	49
IGF1R	-0.02	0.12	-9999	-0.79	22	22
PI4KB	0	0	-9999	-10000	0	0
MFGE8	-0.011	0.089	-9999	-0.62	20	20
SRC	0	0.009	-9999	-0.29	1	1
CDKN1B	-0.088	0.12	-9999	-0.88	11	11
VEGFA	-0.003	0.031	-9999	-0.29	12	12
ILK	-0.086	0.12	-9999	-0.83	8	8
ROCK1	-0.001	0.024	-9999	-0.79	1	1
AKT1	-0.076	0.1	-9999	-0.77	8	8
PTK2B	-0.019	0.093	-9999	-0.48	39	39
alphaV/beta3 Integrin/JAM-A	-0.2	0.24	-9999	-0.48	462	462
CBL	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.019	0.096	-9999	-0.52	38	38
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.14	0.25	-9999	-0.54	270	270
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.013	0.062	-9999	-0.44	10	10
alphaV/beta3 Integrin/Syndecan-1	-0.029	0.1	-9999	-0.53	39	39
PI4KA	0	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.33	0.35	-9999	-0.76	353	353
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-0.29	1	1
alphaV/beta3 Integrin/Osteopontin	-0.056	0.11	-9999	-0.52	41	41
RPS6KB1	-0.3	0.32	-9999	-0.69	354	354
TLN1	0	0	-9999	-10000	0	0
MAPK3	-0.34	0.39	-9999	-0.77	458	458
GPR124	-0.009	0.082	-9999	-0.79	12	12
MAPK1	-0.34	0.39	-9999	-0.77	458	458
PXN	0	0	-9999	-10000	0	0
PIK3R1	-0.009	0.086	-9999	-0.79	13	13
alphaV/beta3 Integrin/Tumstatin	-0.1	0.21	-9999	-0.53	215	215
cell adhesion	-0.023	0.11	-9999	-0.5	48	48
ANGPTL3	-0.001	0.018	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src	-0.004	0.038	-9999	-0.52	5	5
IGF-1R heterotetramer	-0.02	0.12	-9999	-0.79	22	22
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	-0.035	0.16	-9999	-0.79	48	48
ITGB3	-0.029	0.15	-9999	-0.74	42	42
IGF1	-0.18	0.33	-9999	-0.79	246	246
RAC1	0	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.024	0.12	-9999	-0.58	44	44
apoptosis	0	0	-9999	-10000	0	0
CD47	-0.001	0.024	-9999	-0.79	1	1
alphaV/beta3 Integrin/CD47	-0.019	0.096	-9999	-0.52	39	39
VCL	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.05	0.18	-9999	-0.65	80	80
CSF1	-0.005	0.063	-9999	-0.79	7	7
PIK3C2A	-0.087	0.12	-9999	-0.85	9	9
PI4 Kinase/Pyk2	-0.17	0.21	-9999	-0.6	76	76
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.02	0.1	-9999	-0.52	39	39
FAK1/Vinculin	-0.065	0.16	-9999	-0.49	46	46
alphaV beta3/Integrin/ppsTEM5	-0.024	0.12	-9999	-0.58	44	44
RHOA	0	0	-9999	-10000	0	0
VTN	-0.028	0.1	-9999	-0.34	89	89
BCAR1	0	0	-9999	-10000	0	0
FGF2	-0.32	0.39	-9999	-0.79	444	444
F11R	-0.23	0.31	-9999	-0.6	444	444
alphaV/beta3 Integrin/Lactadherin	-0.025	0.12	-9999	-0.55	48	48
alphaV/beta3 Integrin/TGFBR2	-0.04	0.16	-9999	-0.65	67	67
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.003	0.037	-9999	-0.47	7	7
HSP90AA1	0	0.009	-9999	-0.29	1	1
alphaV/beta3 Integrin/Talin	-0.017	0.088	-9999	-0.48	38	38
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.12	0.14	-9999	-0.29	432	432
alphaV/beta3 Integrin/Pyk2	-0.019	0.094	-9999	-0.49	39	39
SDC1	-0.02	0.076	-9999	-0.3	73	73
VAV3	-0.007	0.051	-9999	-0.44	14	14
PTPN11	0	0	-9999	-10000	0	0
IRS1	-0.033	0.16	-9999	-0.79	45	45
FAK1/Paxillin	-0.065	0.16	-9999	-0.49	46	46
cell migration	-0.051	0.14	-9999	-0.44	43	43
ITGAV	0	0	-9999	-10000	0	0
PI3K	-0.19	0.23	-9999	-0.43	465	465
SPP1	-0.077	0.13	-9999	-0.29	288	288
KDR	-0.004	0.053	-9999	-0.79	5	5
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0	0	-9999	-10000	0	0
COL4A3	-0.13	0.29	-9999	-0.78	186	186
angiogenesis	-0.3	0.39	-9999	-0.74	460	460
Rac1/GTP	-0.007	0.046	-9999	-0.4	14	14
EDIL3	-0.051	0.19	-9999	-0.79	65	65
cell proliferation	-0.04	0.16	-9999	-0.65	67	67

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.065	0.22	-9999	-0.62	63	63
CRP	-0.069	0.22	-9999	-0.63	63	63
cell cycle arrest	-0.083	0.24	-9999	-0.7	73	73
TIMP1	-0.062	0.2	-9999	-0.57	56	56
IL6ST	-0.086	0.26	-9999	-0.79	136	136
Rac1/GDP	-0.12	0.23	-9999	-0.65	96	96
AP1	-0.13	0.23	-9999	-0.49	257	257
GAB2	0.005	0.044	-9999	-0.79	2	2
TNFSF11	-0.075	0.22	-9999	-0.63	62	62
HSP90B1	0.015	0.047	-9999	-10000	0	0
GAB1	0.008	0.006	-9999	-10000	0	0
MAPK14	-0.13	0.25	-9999	-0.73	93	93
AKT1	0.038	0.041	-9999	-10000	0	0
FOXO1	0.047	0.058	-9999	-0.4	11	11
MAP2K6	-0.15	0.26	-9999	-0.67	122	122
mol:GTP	0	0.001	-9999	-10000	0	0
MAP2K4	-0.086	0.23	-9999	-0.64	87	87
MITF	-0.14	0.26	-9999	-0.53	187	187
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0	0	-9999	-10000	0	0
A2M	0.014	0.12	-9999	-1.5	7	7
CEBPB	0.016	0.007	-9999	-10000	0	0
GRB2/SOS1/GAB family/SHP2	-0.044	0.094	-9999	-0.59	5	5
STAT3	-0.091	0.26	-9999	-0.76	73	73
STAT1	-0.013	0.021	-9999	-10000	0	0
CEBPD	-0.066	0.22	-9999	-0.64	63	63
PIK3CA	0.012	0.009	-9999	-0.29	1	1
PI3K	-0.007	0.065	-9999	-0.6	13	13
JUN	-0.005	0.063	-9999	-0.79	7	7
PIAS3/MITF	-0.16	0.22	-9999	-0.7	90	90
MAPK11	-0.13	0.25	-9999	-0.73	96	96
STAT3 (dimer)/FOXO1	-0.035	0.22	-9999	-0.56	77	77
GRB2/SOS1/GAB family	-0.14	0.2	-9999	-0.73	67	67
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.16	0.25	-9999	-0.49	232	232
GRB2	0.008	0.011	-9999	-0.29	1	1
JAK2	-0.001	0.024	-9999	-0.79	1	1
LBP	-0.24	0.45	-9999	-0.95	281	281
PIK3R1	0.003	0.087	-9999	-0.79	13	13
JAK1	0.009	0.025	-9999	-0.79	1	1
MYC	-0.078	0.26	-9999	-0.8	69	69
FGG	-0.075	0.22	-9999	-0.62	67	67
macrophage differentiation	-0.083	0.24	-9999	-0.7	73	73
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.23	0.28	-9999	-0.5	503	503
JUNB	-0.064	0.21	-9999	-0.6	62	62
FOS	-0.24	0.36	-9999	-0.79	325	325
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.15	0.26	-9999	-0.47	282	282
STAT1/PIAS1	-0.13	0.23	-9999	-0.57	125	125
GRB2/SOS1/GAB family/SHP2/PI3K	-0.002	0.033	-9999	-0.3	3	3
STAT3 (dimer)	-0.086	0.25	-9999	-0.74	71	71
PRKCD	-0.061	0.22	-9999	-0.6	79	79
IL6R	-0.021	0.16	-9999	-0.79	43	43
SOCS3	-0.12	0.24	-9999	-0.74	85	85
gp130 (dimer)/JAK1/JAK1/LMO4	-0.057	0.18	-9999	-0.52	139	139
Rac1/GTP	-0.15	0.2	-9999	-0.62	105	105
HCK	-0.004	0.033	-9999	-10000	0	0
MAPKKK cascade	-0.006	0.084	-9999	-1	2	2
bone resorption	-0.071	0.21	-9999	-0.6	62	62
IRF1	-0.065	0.22	-9999	-0.63	61	61
mol:GDP	-0.13	0.25	-9999	-0.48	217	217
SOS1	0	0.003	-9999	-10000	0	0
VAV1	-0.13	0.25	-9999	-0.49	217	217
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.16	0.25	-9999	-0.8	91	91
PTPN11	-0.013	0.019	-9999	-10000	0	0
IL6/IL6RA	-0.24	0.31	-9999	-0.63	418	418
gp130 (dimer)/TYK2/TYK2/LMO4	-0.06	0.18	-9999	-0.52	139	139
gp130 (dimer)/JAK2/JAK2/LMO4	-0.06	0.18	-9999	-0.52	139	139
IL6	-0.28	0.39	-9999	-0.79	399	399
PIAS3	0	0	-9999	-10000	0	0
PTPRE	0.003	0.025	-9999	-0.79	1	1
PIAS1	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.18	0.24	-9999	-0.4	502	502
LMO4	0.009	0.049	-9999	-0.44	10	10
STAT3 (dimer)/PIAS3	-0.15	0.21	-9999	-0.77	70	70
MCL1	0.051	0.034	-9999	-10000	0	0

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.16	0.39	-9999	-1	90	90
IL23A	-0.17	0.39	-9999	-1	90	90
NF kappa B1 p50/RelA/I kappa B alpha	-0.23	0.32	-9999	-0.89	134	134
positive regulation of T cell mediated cytotoxicity	-0.18	0.42	-9999	-0.92	172	172
ITGA3	-0.16	0.38	-9999	-0.94	109	109
IL17F	-0.1	0.28	-9999	-0.64	100	100
IL12B	-0.051	0.12	-9999	-0.28	230	230
STAT1 (dimer)	-0.22	0.37	-9999	-0.94	141	141
CD4	-0.16	0.38	-9999	-0.96	89	89
IL23	-0.17	0.38	-9999	-1	89	89
IL23R	-0.012	0.087	-9999	-10000	0	0
IL1B	-0.18	0.41	-9999	-1	110	110
T-helper cell lineage commitment	0	0	-9999	-10000	0	0
IL24	-0.17	0.38	-9999	-0.93	108	108
TYK2	0.011	0.017	-9999	-10000	0	0
STAT4	-0.032	0.16	-9999	-0.78	45	45
STAT3	0	0	-9999	-10000	0	0
IL18RAP	-0.022	0.15	-9999	-0.73	43	43
IL12RB1	-0.002	0.07	-9999	-0.33	37	37
PIK3CA	0	0.009	-9999	-0.29	1	1
IL12Rbeta1/TYK2	-0.002	0.052	-9999	-0.6	2	2
IL23R/JAK2	-0.01	0.11	-9999	-0.64	1	1
positive regulation of chronic inflammatory response	-0.18	0.42	-9999	-0.92	172	172
natural killer cell activation	0.002	0.008	-9999	-10000	0	0
JAK2	0.018	0.034	-9999	-0.83	1	1
PIK3R1	-0.009	0.086	-9999	-0.79	13	13
NFKB1	0.005	0.007	-9999	-10000	0	0
RELA	0.005	0.007	-9999	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.16	0.37	-9999	-0.94	94	94
ALOX12B	-0.16	0.38	-9999	-0.89	130	130
CXCL1	-0.34	0.63	-9999	-1.4	279	279
T cell proliferation	-0.18	0.42	-9999	-0.92	172	172
NFKBIA	0.005	0.007	-9999	-10000	0	0
IL17A	-0.069	0.24	-9999	-0.53	61	61
PI3K	-0.24	0.33	-9999	-0.9	145	145
IFNG	-0.005	0.027	-9999	-0.088	26	26
STAT3 (dimer)	-0.23	0.31	-9999	-0.87	137	137
IL18R1	-0.006	0.1	-9999	-0.79	19	19
IL23/IL23R/JAK2/TYK2/SOCS3	-0.083	0.24	-9999	-0.57	50	50
IL18/IL18R	-0.03	0.12	-9999	-0.53	55	55
macrophage activation	-0.013	0.016	-9999	-0.042	104	104
TNF	-0.18	0.41	-9999	-1.1	96	96
STAT3/STAT4	-0.25	0.35	-9999	-0.92	161	161
STAT4 (dimer)	-0.23	0.39	-9999	-0.98	156	156
IL18	0.001	0.045	-9999	-0.3	24	24
IL19	-0.17	0.38	-9999	-1	85	85
STAT5A (dimer)	-0.22	0.37	-9999	-0.92	153	153
STAT1	-0.005	0.038	-9999	-0.29	19	19
SOCS3	-0.004	0.058	-9999	-0.79	6	6
CXCL9	-0.18	0.38	-9999	-0.98	99	99
MPO	-0.21	0.47	-9999	-1.1	149	149
positive regulation of humoral immune response	-0.18	0.42	-9999	-0.92	172	172
IL23/IL23R/JAK2/TYK2	-0.19	0.44	-9999	-1	146	146
IL6	-0.46	0.7	-9999	-1.3	407	407
STAT5A	-0.006	0.067	-9999	-0.79	8	8
IL2	0.004	0.028	-9999	-0.3	8	8
positive regulation of tyrosine phosphorylation of STAT protein	0.002	0.008	-9999	-10000	0	0
CD3E	-0.17	0.41	-9999	-0.98	130	130
keratinocyte proliferation	-0.18	0.42	-9999	-0.92	172	172
NOS2	-0.16	0.39	-9999	-0.95	109	109

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0	0	-9999	-10000	0	0
GNAT1/GTP	-0.003	0.023	-9999	-10000	0	0
Metarhodopsin II/Arrestin	-0.01	0.04	-9999	-0.31	2	2
PDE6G/GNAT1/GTP	-0.009	0.036	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	-0.004	0.034	-9999	-0.29	15	15
GRK1	-0.003	0.029	-9999	-0.29	11	11
CNG Channel	-0.14	0.2	-9999	-0.43	316	316
mol:Na +	-0.13	0.18	-9999	-0.42	309	309
mol:ADP	-0.003	0.029	-9999	-0.29	11	11
RGS9-1/Gbeta5/R9AP	-0.062	0.16	-9999	-0.53	107	107
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.13	0.19	-9999	-0.43	309	309
CNGB1	-0.015	0.064	-9999	-10000	0	0
RDH5	-0.48	0.39	-9999	-0.79	658	658
SAG	-0.015	0.064	-9999	-0.29	55	55
mol:Ca2+	-0.12	0.18	-9999	-0.53	22	22
Na + (4 Units)	-0.12	0.17	-9999	-0.51	22	22
RGS9	-0.081	0.24	-9999	-0.73	122	122
GNB1/GNGT1	-0.03	0.068	-9999	-10000	0	0
GNAT1/GDP	-0.055	0.14	-9999	-0.46	107	107
GUCY2D	-0.008	0.061	-9999	-0.38	23	23
GNGT1	-0.047	0.11	-9999	-0.29	175	175
GUCY2F	-0.001	0.013	-9999	-10000	0	0
GNB5	0	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.019	0.071	-9999	-0.45	23	23
mol:11-cis-retinal	-0.48	0.39	-9999	-0.79	658	658
mol:cGMP	-0.011	0.05	-9999	-0.45	9	9
GNB1	0	0	-9999	-10000	0	0
Rhodopsin	-0.37	0.3	-9999	-0.61	658	658
SLC24A1	0	0	-9999	-10000	0	0
CNGA1	-0.22	0.35	-9999	-0.78	310	310
Metarhodopsin II	-0.003	0.022	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.012	0.053	-9999	-0.48	9	9
RGS9BP	-0.019	0.073	-9999	-10000	0	0
Metarhodopsin II/Transducin	-0.009	0.021	-9999	-10000	0	0
GCAP Family/Ca ++	-0.008	0.043	-9999	-0.49	5	5
PDE6A/B	-0.017	0.091	-9999	-0.6	23	23
mol:Pi	-0.062	0.16	-9999	-0.53	107	107
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.023	0.051	-9999	-0.28	2	2
PDE6B	-0.017	0.11	-9999	-0.79	23	23
PDE6A	-0.006	0.042	-9999	-0.29	23	23
PDE6G	-0.012	0.058	-9999	-0.29	45	45
RHO	-0.004	0.035	-9999	-0.29	16	16
PDE6	-0.063	0.14	-9999	-0.62	18	18
GUCA1A	-0.012	0.059	-9999	-0.29	46	46
GC2/GCAP Family	-0.008	0.043	-9999	-0.49	5	5
GUCA1C	0	0.009	-9999	-0.29	1	1
GUCA1B	-0.004	0.053	-9999	-0.79	5	5

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.023	0.062	-9999	-0.56	11	11
alphaM/beta2 Integrin/GPIbA	-0.024	0.058	-9999	-0.53	9	9
alphaM/beta2 Integrin/proMMP-9	-0.083	0.082	-9999	-0.39	8	8
PLAUR	-0.022	0.078	-9999	-0.29	83	83
HMGB1	-0.013	0.017	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.017	0.029	-9999	-10000	0	0
AGER	-0.015	0.041	-9999	-0.66	3	3
RAP1A	0	0	-9999	-10000	0	0
SELPLG	0	0	-9999	-10000	0	0
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.074	0.096	-9999	-0.39	13	13
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.13	0.15	-9999	-0.29	484	484
CYR61	-0.042	0.18	-9999	-0.79	58	58
TLN1	0	0	-9999	-10000	0	0
Rap1/GTP	-0.057	0.11	-9999	-0.52	22	22
RHOA	0	0	-9999	-10000	0	0
P-selectin oligomer	-0.18	0.33	-9999	-0.79	256	256
MYH2	-0.07	0.16	-9999	-0.5	47	47
MST1R	-0.011	0.083	-9999	-0.55	21	21
leukocyte activation during inflammatory response	-0.29	0.22	-9999	-0.47	664	664
APOB	-0.48	0.38	-9999	-0.79	664	664
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.008	0.079	-9999	-0.75	12	12
JAM3	-0.005	0.063	-9999	-0.79	7	7
GP1BA	-0.012	0.077	-9999	-0.4	33	33
alphaM/beta2 Integrin/CTGF	-0.025	0.069	-9999	-0.58	14	14
alphaM/beta2 Integrin	-0.072	0.13	-9999	-0.36	94	94
JAM3 homodimer	-0.005	0.063	-9999	-0.79	7	7
ICAM2	-0.004	0.053	-9999	-0.79	5	5
ICAM1	-0.004	0.035	-9999	-0.29	16	16
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.061	0.14	-9999	-0.36	95	95
cell adhesion	-0.024	0.057	-9999	-0.52	9	9
NFKB1	-0.096	0.21	-9999	-0.66	15	15
THY1	-0.002	0.025	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.32	0.26	-9999	-0.53	664	664
alphaM/beta2 Integrin/LRP/tPA	-0.034	0.11	-9999	-0.54	46	46
IL6	-0.3	0.48	-9999	-0.93	399	399
ITGB2	-0.017	0.039	-9999	-0.3	16	16
elevation of cytosolic calcium ion concentration	-0.025	0.05	-9999	-0.4	1	1
alphaM/beta2 Integrin/JAM2/JAM3	-0.044	0.13	-9999	-0.54	67	67
JAM2	-0.047	0.19	-9999	-0.79	65	65
alphaM/beta2 Integrin/ICAM1	-0.021	0.08	-9999	-0.53	21	21
alphaM/beta2 Integrin/uPA/Plg	-0.019	0.033	-9999	-10000	0	0
RhoA/GTP	-0.088	0.16	-9999	-0.43	119	119
positive regulation of phagocytosis	-0.045	0.092	-9999	-0.46	19	19
Ron/MSP	-0.016	0.098	-9999	-0.66	22	22
alphaM/beta2 Integrin/uPAR/uPA	-0.025	0.05	-9999	-0.4	1	1
alphaM/beta2 Integrin/uPAR	-0.028	0.048	-9999	-0.39	2	2
PLAU	-0.008	0.047	-9999	-0.29	29	29
PLAT	-0.029	0.15	-9999	-0.74	42	42
actin filament polymerization	-0.067	0.15	-9999	-0.47	51	51
MST1	-0.012	0.089	-9999	-0.6	21	21
alphaM/beta2 Integrin/lipoprotein(a)	-0.29	0.22	-9999	-0.47	664	664
TNF	-0.087	0.22	-9999	-0.87	21	21
RAP1B	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.021	0.036	-9999	-10000	0	0
fibrinolysis	-0.019	0.033	-9999	-10000	0	0
HCK	-0.004	0.033	-9999	-10000	0	0
dendritic cell antigen processing and presentation	-0.061	0.14	-9999	-0.36	95	95
VTN	-0.028	0.1	-9999	-0.34	89	89
alphaM/beta2 Integrin/CYR61	-0.046	0.13	-9999	-0.57	58	58
LPA	-0.001	0.02	-9999	-0.29	5	5
LRP1	-0.009	0.082	-9999	-0.79	12	12
cell migration	-0.073	0.084	-9999	-0.47	16	16
FN1	-0.12	0.14	-9999	-0.29	432	432
alphaM/beta2 Integrin/Thy1	-0.018	0.031	-9999	-10000	0	0
MPO	-0.053	0.2	-9999	-0.77	75	75
KNG1	-0.006	0.041	-9999	-0.29	22	22
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.066	0.16	-9999	-0.41	106	106
ELA2	0	0	-9999	-10000	0	0
PLG	-0.002	0.025	-9999	-0.29	8	8
CTGF	-0.011	0.09	-9999	-0.7	17	17
alphaM/beta2 Integrin/Hck	-0.019	0.035	-9999	-10000	0	0
ITGAM	-0.015	0.028	-9999	-0.31	6	6
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.13	0.21	-9999	-0.5	256	256
HP	-0.16	0.31	-9999	-0.79	204	204
leukocyte adhesion	-0.076	0.13	-9999	-0.58	45	45
SELP	-0.18	0.34	-9999	-0.79	256	256

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0.096	0.2	0.63	120	-10000	0	120
KIRREL	-0.081	0.25	-10000	0	-0.8	120	120
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.096	0.2	-10000	0	-0.63	120	120
PLCG1	0	0	-10000	0	-10000	0	0
ARRB2	0	0	-10000	0	-10000	0	0
WASL	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.07	0.15	-10000	0	-0.48	120	120
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.043	0.11	-10000	0	-0.36	120	120
FYN	-0.065	0.14	-10000	0	-0.46	120	120
mol:Ca2+	-0.069	0.15	-10000	0	-0.48	120	120
mol:DAG	-0.069	0.15	-10000	0	-0.48	120	120
NPHS2	-0.008	0.031	-10000	0	-0.29	5	5
mol:IP3	-0.069	0.15	-10000	0	-0.48	120	120
regulation of endocytosis	-0.055	0.14	-10000	0	-0.43	120	120
Nephrin/NEPH1/podocin/Cholesterol	-0.072	0.15	-10000	0	-0.49	121	121
establishment of cell polarity	-0.096	0.2	-10000	0	-0.63	120	120
Nephrin/NEPH1/podocin/NCK1-2	-0.062	0.14	-10000	0	-0.44	120	120
Nephrin/NEPH1/beta Arrestin2	-0.056	0.14	-10000	0	-0.43	120	120
NPHS1	-0.047	0.11	-10000	0	-0.29	179	179
Nephrin/NEPH1/podocin	-0.065	0.14	-10000	0	-0.46	120	120
TJP1	-0.001	0.024	-10000	0	-0.79	1	1
NCK1	0	0	-10000	0	-10000	0	0
NCK2	0	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.07	0.15	-10000	0	-0.48	120	120
CD2AP	0	0.009	-10000	0	-0.29	1	1
Nephrin/NEPH1/podocin/GRB2	-0.07	0.15	-10000	0	-0.48	120	120
GRB2	0	0.009	-10000	0	-0.29	1	1
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.057	0.17	-10000	0	-0.5	129	129
cytoskeleton organization	-0.055	0.14	-10000	0	-0.45	120	120
Nephrin/NEPH1	-0.07	0.15	-10000	0	-0.47	120	120
Nephrin/NEPH1/ZO-1	-0.076	0.16	-10000	0	-0.52	120	120

×

Ephrin A reverse signaling

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
MAPKKK cascade	-0.051	0.16	-9999	-0.53	104	104
EFNA5	-0.076	0.23	-9999	-0.78	105	105
FYN	-0.027	0.15	-9999	-0.48	105	105
neuron projection morphogenesis	-0.051	0.16	-9999	-0.53	104	104
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.051	0.16	-9999	-0.53	104	104
EPHA5	-0.001	0.02	-9999	-0.29	5	5

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.017	0.031	-9999	-10000	0	0
VDR	0	0	-9999	-10000	0	0
FAM120B	0	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.033	0.16	-9999	-0.42	19	19
RXRs/LXRs/DNA/Oxysterols	-0.013	0.14	-9999	-0.42	33	33
MED1	-0.006	0.043	-9999	-0.29	24	24
mol:9cRA	0.005	0.008	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	-0.023	0.091	-9999	-0.35	71	71
RXRs/NUR77	-0.15	0.24	-9999	-0.5	327	327
RXRs/PPAR	-0.13	0.23	-9999	-0.38	448	448
NCOR2	0	0	-9999	-10000	0	0
VDR/VDR/Vit D3	0	0	-9999	-10000	0	0
RARs/VDR/DNA/Vit D3	-0.007	0.052	-9999	-0.45	14	14
RARA	-0.004	0.034	-9999	-0.29	15	15
NCOA1	-0.001	0.024	-9999	-0.79	1	1
VDR/VDR/DNA	0	0	-9999	-10000	0	0
RARs/RARs/DNA/9cRA	-0.007	0.052	-9999	-0.45	14	14
RARG	0	0	-9999	-10000	0	0
RPS6KB1	0.029	0.052	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	-0.023	0.088	-9999	-0.34	71	71
THRA	-0.001	0.024	-9999	-0.79	1	1
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	0	0	-9999	-10000	0	0
RXRs/PPAR/9cRA/PGJ2/DNA	-0.12	0.2	-9999	-0.46	265	265
NR1H4	-0.003	0.032	-9999	-0.29	13	13
RXRs/LXRs/DNA	-0.1	0.18	-9999	-0.42	265	265
NR1H2	0.016	0.006	-9999	-10000	0	0
NR1H3	0.016	0.007	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.11	0.19	-9999	-0.44	265	265
NR4A1	-0.065	0.22	-9999	-0.79	90	90
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.042	0.13	-9999	-0.27	265	265
RXRG	-0.18	0.34	-9999	-0.78	268	268
RXR alpha/CCPG	0	0	-9999	-10000	0	0
RXRA	0.016	0.006	-9999	-10000	0	0
RXRB	0.016	0.007	-9999	-10000	0	0
THRB	-0.044	0.18	-9999	-0.79	61	61
PPARG	-0.19	0.34	-9999	-0.79	263	263
PPARD	0	0	-9999	-10000	0	0
TNF	-0.014	0.19	-9999	-1.2	14	14
mol:Oxysterols	0.005	0.007	-9999	-10000	0	0
cholesterol transport	-0.013	0.14	-9999	-0.42	33	33
PPARA	-0.005	0.063	-9999	-0.79	7	7
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	-0.01	0.089	-9999	-0.79	14	14
RXRs/NUR77/BCL2	-0.12	0.19	-9999	-0.37	349	349
SREBF1	-0.004	0.14	-9999	-0.63	7	7
RXRs/RXRs/DNA/9cRA	-0.12	0.2	-9999	-0.46	265	265
ABCA1	-0.008	0.16	-9999	-0.96	12	12
RARs/THRs	-0.032	0.12	-9999	-0.47	71	71
RXRs/FXR	-0.11	0.2	-9999	-0.47	265	265
BCL2	-0.027	0.14	-9999	-0.79	37	37

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.005	0.046	-9999	-0.62	5	5
PDGFRB	0.005	0.049	-9999	-0.8	4	4
SPHK1	-0.025	0.055	-9999	-1.1	2	2
mol:S1P	-0.031	0.058	-9999	-0.97	2	2
S1P1/S1P/Gi	-0.1	0.23	-9999	-0.39	381	381
GNAO1	-0.023	0.14	-9999	-0.5	67	67
PDGFB-D/PDGFRB/PLCgamma1	-0.12	0.18	-9999	-0.59	77	77
PLCG1	-0.091	0.22	-9999	-0.62	76	76
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.005	0.049	-9999	-0.79	4	4
GNAI2	0.008	0.006	-9999	-10000	0	0
GNAI3	0.008	0.006	-9999	-10000	0	0
GNAI1	-0.038	0.19	-9999	-0.8	62	62
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.006	0.043	-9999	-0.54	5	5
S1P1/S1P	-0.044	0.074	-9999	-0.61	7	7
negative regulation of cAMP metabolic process	-0.098	0.22	-9999	-0.38	381	381
MAPK3	-0.16	0.31	-9999	-0.58	371	371
calcium-dependent phospholipase C activity	-0.003	0.004	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
KDR	-0.004	0.054	-9999	-0.8	5	5
PLCB2	-0.008	0.086	-9999	-0.53	8	8
RAC1	0	0	-9999	-10000	0	0
RhoA/GTP	-0.038	0.061	-9999	-0.5	7	7
receptor internalization	-0.043	0.069	-9999	-0.56	7	7
PTGS2	-0.33	0.55	-9999	-1.1	371	371
Rac1/GTP	-0.038	0.061	-9999	-0.5	7	7
RHOA	0	0	-9999	-10000	0	0
VEGFA	-0.003	0.031	-9999	-0.29	12	12
negative regulation of T cell proliferation	-0.098	0.22	-9999	-0.38	381	381
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.001	0.073	-9999	-0.8	9	9
MAPK1	-0.16	0.31	-9999	-0.58	371	371
S1P1/S1P/PDGFB-D/PDGFRB	-0.02	0.11	-9999	-0.67	9	9
ABCC1	0	0	-9999	-10000	0	0

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	-0.06	0.12	-9999	-0.29	223	223
mol:Halofuginone	0	0.003	-9999	-10000	0	0
ITGA1	-0.007	0.075	-9999	-0.79	10	10
CDKN1A	-0.056	0.088	-9999	-0.84	2	2
PRL-3/alpha Tubulin	-0.002	0.019	-9999	-10000	0	0
mol:Ca2+	-0.033	0.097	-9999	-0.62	15	15
AGT	-0.048	0.13	-9999	-0.34	152	152
CCNA2	-0.16	0.24	-9999	-0.49	345	345
TUBA1B	0	0	-9999	-10000	0	0
EGR1	-0.17	0.29	-9999	-0.6	345	345
CDK2/Cyclin E1	-0.067	0.09	-9999	-0.82	2	2
MAPK3	0.02	0.021	-9999	-10000	0	0
PRL-2 /Rab GGTase beta	0	0.006	-9999	-10000	0	0
MAPK1	0.02	0.021	-9999	-10000	0	0
PTP4A1	-0.12	0.23	-9999	-0.46	345	345
PTP4A3	-0.003	0.029	-9999	-10000	0	0
PTP4A2	0	0.009	-9999	-10000	0	0
ITGB1	0.02	0.021	-9999	-10000	0	0
SRC	0	0.009	-9999	-0.29	1	1
RAC1	-0.055	0.081	-9999	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0	0	-9999	-10000	0	0
PRL-1/ATF-5	-0.14	0.2	-9999	-0.42	345	345
RABGGTA	0	0	-9999	-10000	0	0
BCAR1	0.001	0.009	-9999	-10000	0	0
RHOC	-0.055	0.081	-9999	-10000	0	0
RHOA	-0.055	0.081	-9999	-10000	0	0
cell motility	-0.034	0.1	-9999	-0.24	1	1
PRL-1/alpha Tubulin	-0.13	0.2	-9999	-0.42	345	345
PRL-3/alpha1 Integrin	-0.007	0.06	-9999	-0.6	10	10
ROCK1	-0.034	0.1	-9999	-0.24	1	1
RABGGTB	0	0	-9999	-10000	0	0
CDK2	0	0	-9999	-10000	0	0
mitosis	-0.12	0.23	-9999	-0.46	345	345
ATF5	-0.001	0.018	-9999	-0.29	4	4

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.002	0.027	-9999	-0.29	9	9
Syndecan-3/Src/Cortactin	-0.18	0.2	-9999	-0.4	477	477
Syndecan-3/Neurocan	-0.007	0.028	-9999	-10000	0	0
POMC	-0.024	0.12	-9999	-0.49	53	53
EGFR	-0.3	0.38	-9999	-0.78	414	414
Syndecan-3/EGFR	-0.17	0.21	-9999	-0.44	409	409
AGRP	-0.003	0.028	-9999	-0.29	10	10
NCSTN	0	0	-9999	-10000	0	0
PSENEN	0	0.009	-9999	-0.29	1	1
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	-0.001	0.024	-9999	-0.79	1	1
APH1A	0	0	-9999	-10000	0	0
NCAN	-0.019	0.073	-9999	-0.29	72	72
long-term memory	-0.002	0.02	-9999	-0.41	2	2
Syndecan-3/IL8	-0.016	0.067	-9999	-0.44	22	22
PSEN1	0	0	-9999	-10000	0	0
Src/Cortactin	-0.002	0.018	-9999	-10000	0	0
FYN	-0.001	0.034	-9999	-0.79	2	2
limb bud formation	0	0.003	-9999	-10000	0	0
MC4R	-0.003	0.032	-9999	-0.29	13	13
SRC	0	0.009	-9999	-0.29	1	1
PTN	-0.35	0.39	-9999	-0.79	479	479
FGFR/FGF/Syndecan-3	0	0.003	-9999	-10000	0	0
neuron projection morphogenesis	-0.18	0.19	-9999	-0.39	477	477
Syndecan-3/AgRP	-0.001	0.011	-9999	-10000	0	0
Syndecan-3/AgRP/MC4R	-0.002	0.015	-9999	-10000	0	0
Fyn/Cortactin	-0.003	0.031	-9999	-0.6	2	2
SDC3	0	0.003	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.015	0.066	-9999	-0.43	22	22
IL8	-0.033	0.13	-9999	-0.79	22	22
Syndecan-3/Fyn/Cortactin	-0.002	0.02	-9999	-0.42	2	2
Syndecan-3/CASK	0	0.003	-9999	-10000	0	0
alpha-MSH/MC4R	-0.019	0.093	-9999	-0.6	23	23
Gamma Secretase	0	0.014	-9999	-0.44	1	1

×

LPA receptor mediated 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
GNB1/GNG2	-0.019	0.094	-9999	-0.5	36	36
NF kappa B1 p50/RelA/I kappa B alpha	-0.043	0.11	-9999	-0.46	6	6
AP1	-0.18	0.25	-9999	-0.47	419	419
mol:PIP3	-0.2	0.24	-9999	-0.45	467	467
AKT1	-0.016	0.075	-9999	-0.59	8	8
PTK2B	0.014	0.062	-9999	-0.29	26	26
RHOA	0.028	0.028	-9999	-10000	0	0
PIK3CB	0	0	-9999	-10000	0	0
mol:Ca2+	-0.007	0.13	-9999	-0.35	128	128
MAGI3	-0.001	0.034	-9999	-0.79	2	2
RELA	0	0	-9999	-10000	0	0
apoptosis	-0.062	0.15	-9999	-0.42	148	148
HRAS/GDP	-0.002	0.018	-9999	-10000	0	0
positive regulation of microtubule depolymerization	-0.02	0.15	-9999	-0.4	126	126
NF kappa B1 p50/RelA	-0.053	0.14	-9999	-0.55	16	16
endothelial cell migration	0.007	0.12	-9999	-0.63	34	34
ADCY4	-0.004	0.15	-9999	-0.63	41	41
ADCY5	-0.071	0.19	-9999	-0.59	81	81
ADCY6	0.006	0.13	-9999	-0.6	31	31
ADCY7	0.006	0.13	-9999	-0.6	31	31
ADCY1	-0.003	0.14	-9999	-0.64	37	37
ADCY2	-0.015	0.16	-9999	-0.62	49	49
ADCY3	0.006	0.13	-9999	-0.6	31	31
ADCY8	0.003	0.13	-9999	-0.61	31	31
ADCY9	0.006	0.13	-9999	-0.6	31	31
GSK3B	0.021	0.059	-9999	-0.36	10	10
arachidonic acid secretion	0.009	0.13	-9999	-0.56	34	34
GNG2	-0.009	0.086	-9999	-0.79	13	13
TRIP6	-0.001	0.016	-9999	-0.51	1	1
GNAO1	-0.006	0.13	-9999	-0.53	56	56
HRAS	-0.002	0.027	-9999	-0.29	9	9
NFKBIA	-0.003	0.15	-9999	-0.4	128	128
GAB1	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	0.001	0.004	-9999	-10000	0	0
JUN	-0.005	0.063	-9999	-0.79	7	7
LPA/LPA2/NHERF2	-0.002	0.016	-9999	-10000	0	0
TIAM1	0.001	0.004	-9999	-10000	0	0
PIK3R1	-0.009	0.086	-9999	-0.79	13	13
mol:IP3	-0.007	0.13	-9999	-0.36	128	128
PLCB3	0.026	0.016	-9999	-10000	0	0
FOS	-0.24	0.36	-9999	-0.79	325	325
positive regulation of mitosis	0.009	0.13	-9999	-0.56	34	34
LPA/LPA1-2-3	-0.073	0.17	-9999	-0.49	147	147
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
stress fiber formation	0.002	0.1	-9999	-0.38	25	25
GNAZ	0.008	0.1	-9999	-0.48	42	42
EGFR/PI3K-beta/Gab1	-0.21	0.26	-9999	-0.48	464	464
positive regulation of dendritic cell cytokine production	-0.072	0.17	-9999	-0.48	147	147
LPA/LPA2/MAGI-3	-0.002	0.025	-9999	-0.52	2	2
ARHGEF1	-0.011	0.069	-9999	-0.44	24	24
GNAI2	0.013	0.087	-9999	-0.46	34	34
GNAI3	0.013	0.087	-9999	-0.46	34	34
GNAI1	-0.018	0.16	-9999	-0.53	89	89
LPA/LPA3	-0.08	0.2	-9999	-0.61	128	128
LPA/LPA2	-0.002	0.016	-9999	-10000	0	0
LPA/LPA1	-0.017	0.096	-9999	-0.54	34	34
HB-EGF/EGFR	-0.26	0.26	-9999	-0.57	414	414
HBEGF	-0.072	0.11	-9999	-0.6	3	3
mol:DAG	-0.007	0.13	-9999	-0.36	128	128
cAMP biosynthetic process	-0.012	0.15	-9999	-0.56	55	55
NFKB1	0	0	-9999	-10000	0	0
SRC	0	0.009	-9999	-0.29	1	1
GNB1	0	0	-9999	-10000	0	0
LYN	-0.003	0.15	-9999	-0.4	128	128
GNAQ	-0.053	0.13	-9999	-0.41	131	131
LPAR2	-0.001	0.015	-9999	-0.29	2	2
LPAR3	-0.1	0.26	-9999	-0.79	128	128
LPAR1	-0.019	0.12	-9999	-0.79	24	24
IL8	-0.19	0.23	-9999	-0.46	354	354
PTK2	-0.067	0.16	-9999	-0.45	147	147
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.062	0.15	-9999	-0.42	148	148
EGFR	-0.3	0.38	-9999	-0.78	414	414
PLCG1	-0.029	0.15	-9999	-0.42	128	128
PLD2	-0.067	0.16	-9999	-0.45	147	147
G12/G13	-0.013	0.075	-9999	-0.48	24	24
PI3K-beta	-0.018	0.089	-9999	-0.72	8	8
cell migration	-0.021	0.053	-9999	-0.24	6	6
SLC9A3R2	-0.001	0.02	-9999	-0.29	5	5
PXN	0.002	0.1	-9999	-0.39	25	25
HRAS/GTP	-0.035	0.12	-9999	-0.58	34	34
RAC1	0	0	-9999	-10000	0	0
MMP9	-0.13	0.15	-9999	-0.29	484	484
PRKCE	0.01	0.002	-9999	-10000	0	0
PRKCD	0.001	0.12	-9999	-0.4	8	8
Gi(beta/gamma)	-0.036	0.12	-9999	-0.57	39	39
mol:LPA	-0.002	0.021	-9999	-0.22	10	10
TRIP6/p130 Cas/FAK1/Paxillin	-0.055	0.14	-9999	-0.66	10	10
MAPKKK cascade	0.009	0.13	-9999	-0.56	34	34
contractile ring contraction involved in cytokinesis	0.028	0.028	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.058	0.14	-9999	-0.42	136	136
GNA15	-0.053	0.13	-9999	-0.41	129	129
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
MAPT	-0.022	0.15	-9999	-0.41	126	126
GNA11	-0.053	0.13	-9999	-0.41	131	131
Rac1/GTP	0.001	0.005	-9999	-10000	0	0
MMP2	0.007	0.12	-9999	-0.64	34	34

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.053	0.3	-10000	0	-0.81	131	131
IHH	-0.014	0.082	-10000	0	-0.42	9	9
SHH Np/Cholesterol/GAS1	-0.032	0.12	-10000	0	-0.49	65	65
LRPAP1	0	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.031	0.12	0.49	65	-10000	0	65
SMO/beta Arrestin2	-0.075	0.23	-10000	0	-0.84	81	81
SMO	-0.036	0.26	-10000	0	-0.85	90	90
AKT1	0.007	0.12	-10000	0	-0.44	22	22
ARRB2	0	0	-10000	0	-10000	0	0
BOC	-0.059	0.21	-10000	0	-0.79	82	82
ADRBK1	0	0	-10000	0	-10000	0	0
heart looping	-0.034	0.25	-10000	0	-0.82	90	90
STIL	-0.038	0.21	-10000	0	-0.68	88	88
DHH N/PTCH2	-0.063	0.19	-10000	0	-0.64	107	107
DHH N/PTCH1	-0.089	0.24	-10000	0	-0.74	115	115
PIK3CA	0	0.009	-10000	0	-0.29	1	1
DHH	-0.022	0.13	-10000	0	-0.76	32	32
PTHLH	-0.081	0.38	-10000	0	-1.1	131	131
determination of left/right symmetry	-0.034	0.25	-10000	0	-0.82	90	90
PIK3R1	-0.009	0.086	-10000	0	-0.79	13	13
skeletal system development	-0.079	0.37	-10000	0	-1	131	131
IHH N/Hhip	-0.015	0.049	-10000	0	-0.41	6	6
DHH N/Hhip	-0.019	0.1	-10000	0	-0.61	32	32
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.034	0.25	-10000	0	-0.82	90	90
pancreas development	-0.004	0.042	-10000	0	-0.39	10	10
HHAT	-0.001	0.024	-10000	0	-0.79	1	1
PI3K	-0.007	0.066	-10000	0	-0.6	13	13
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.046	0.19	-10000	0	-0.79	64	64
somite specification	-0.034	0.25	-10000	0	-0.82	90	90
SHH Np/Cholesterol/PTCH1	-0.071	0.2	-10000	0	-0.7	94	94
SHH Np/Cholesterol/PTCH2	-0.04	0.13	-10000	0	-0.49	85	85
SHH Np/Cholesterol/Megalin	-0.14	0.21	-10000	0	-0.49	291	291
SHH	0.01	0.036	-10000	0	-0.61	1	1
catabolic process	-0.047	0.26	-10000	0	-0.82	96	96
SMO/Vitamin D3	-0.074	0.22	-10000	0	-0.79	86	86
SHH Np/Cholesterol/Hhip	-0.005	0.036	-10000	0	-0.37	7	7
LRP2	-0.22	0.35	-10000	0	-0.75	317	317
receptor-mediated endocytosis	-0.15	0.25	-10000	0	-0.81	100	100
SHH Np/Cholesterol/BOC	-0.04	0.13	-10000	0	-0.49	83	83
SHH Np/Cholesterol/CDO	-0.01	0.061	-10000	0	-0.48	16	16
mesenchymal cell differentiation	0.005	0.035	0.36	7	-10000	0	7
mol:Vitamin D3	-0.029	0.22	-10000	0	-0.7	94	94
IHH N/PTCH2	-0.063	0.18	-10000	0	-0.66	88	88
CDON	-0.011	0.092	-10000	0	-0.79	15	15
IHH N/PTCH1	-0.044	0.26	-10000	0	-0.82	96	96
Megalin/LRPAP1	-0.16	0.26	-10000	0	-0.6	290	290
PTCH2	-0.061	0.21	-10000	0	-0.79	84	84
SHH Np/Cholesterol	-0.003	0.025	-10000	0	-0.49	1	1
PTCH1	-0.047	0.26	-10000	0	-0.82	96	96
HHIP	-0.004	0.042	-10000	0	-0.39	10	10

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	-0.001	0.034	-9999	-0.79	2	2
LAT2	-0.063	0.14	-9999	-0.43	95	95
AP1	-0.15	0.21	-9999	-0.43	347	347
mol:PIP3	-0.027	0.2	-9999	-0.49	107	107
IKBKB	0.002	0.12	-9999	-0.32	54	54
AKT1	-0.082	0.17	-9999	-0.67	45	45
IKBKG	0.002	0.12	-9999	-0.32	54	54
MS4A2	-0.069	0.22	-9999	-0.76	99	99
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-0.3	1	1
MAP3K1	0.006	0.13	-9999	-0.44	45	45
mol:Ca2+	-0.013	0.15	-9999	-0.36	108	108
LYN	0.011	0.004	-9999	-10000	0	0
CBLB	-0.062	0.14	-9999	-0.43	95	95
SHC1	0	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.062	0.16	-9999	-0.48	141	141
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0	0	-9999	-10000	0	0
PLD2	-0.096	0.21	-9999	-0.48	216	216
PTPN13	-0.031	0.17	-9999	-0.54	68	68
PTPN11	0.01	0.006	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	0.006	0.15	-9999	-0.41	44	44
SYK	0.011	0.01	-9999	-0.3	1	1
GRB2	0	0.009	-9999	-0.29	1	1
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.086	0.18	-9999	-0.43	216	216
LAT	-0.064	0.14	-9999	-0.43	96	96
PAK2	-0.004	0.14	-9999	-0.5	45	45
NFATC2	-0.1	0.24	-9999	-0.69	130	130
HRAS	-0.013	0.15	-9999	-0.41	98	98
GAB2	-0.004	0.043	-9999	-0.79	2	2
PLA2G1B	0.028	0.018	-9999	-10000	0	0
Fc epsilon R1	-0.12	0.25	-9999	-0.6	216	216
Antigen/IgE/Fc epsilon R1	-0.11	0.23	-9999	-0.55	216	216
mol:GDP	-0.02	0.16	-9999	-0.42	98	98
JUN	-0.005	0.063	-9999	-0.79	7	7
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	-0.009	0.086	-9999	-0.79	13	13
FOS	-0.24	0.36	-9999	-0.79	325	325
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.067	0.15	-9999	-0.45	98	98
CHUK	0.002	0.12	-9999	-0.32	55	55
KLRG1	-0.062	0.14	-9999	-0.4	99	99
VAV1	-0.064	0.14	-9999	-0.44	98	98
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.062	0.14	-9999	-0.43	95	95
negative regulation of mast cell degranulation	-0.056	0.12	-9999	-0.51	43	43
BTK	-0.061	0.14	-9999	-0.43	97	97
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.086	0.2	-9999	-0.43	218	218
GAB2/PI3K/SHP2	-0.091	0.19	-9999	-0.74	47	47
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.069	0.16	-9999	-0.6	53	53
RAF1	0.015	0.022	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.1	0.22	-9999	-0.51	218	218
FCER1G	0.003	0.013	-9999	-0.29	1	1
FCER1A	-0.11	0.29	-9999	-0.8	160	160
Antigen/IgE/Fc epsilon R1/Fyn	-0.1	0.22	-9999	-0.52	216	216
MAPK3	0.026	0.019	-9999	-10000	0	0
MAPK1	0.026	0.019	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
MAPK8	0.01	0.078	-9999	-0.67	9	9
DUSP1	-0.1	0.26	-9999	-0.79	141	141
NF-kappa-B/RelA	-0.027	0.054	-9999	-0.23	6	6
actin cytoskeleton reorganization	-0.027	0.15	-9999	-0.42	95	95
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.059	0.13	-9999	-0.52	54	54
FER	-0.066	0.15	-9999	-0.45	102	102
RELA	0	0	-9999	-10000	0	0
ITK	-0.035	0.11	-9999	-0.6	39	39
SOS1	0	0	-9999	-10000	0	0
PLCG1	-0.017	0.16	-9999	-0.44	98	98
cytokine secretion	-0.019	0.04	-9999	-10000	0	0
SPHK1	-0.065	0.14	-9999	-0.44	98	98
PTK2	-0.029	0.16	-9999	-0.57	45	45
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.089	0.19	-9999	-0.45	216	216
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.022	0.2	-9999	-0.48	107	107
MAP2K2	0.023	0.019	-9999	-10000	0	0
MAP2K1	0.023	0.019	-9999	-10000	0	0
MAP2K7	0	0	-9999	-10000	0	0
KLRG1/SHP2	-0.058	0.13	-9999	-0.51	43	43
MAP2K4	0.017	0.033	-9999	-1	1	1
Fc epsilon R1/FcgammaRIIB	-0.11	0.23	-9999	-0.55	218	218
mol:Choline	-0.094	0.2	-9999	-0.47	216	216
SHC/Grb2/SOS1	-0.056	0.13	-9999	-0.54	41	41
FYN	-0.001	0.034	-9999	-0.79	2	2
DOK1	-0.001	0.018	-9999	-10000	0	0
PXN	-0.019	0.15	-9999	-0.54	41	41
HCLS1	-0.062	0.14	-9999	-0.43	95	95
PRKCB	-0.015	0.16	-9999	-0.38	104	104
FCGR2B	-0.004	0.054	-9999	-0.71	6	6
IGHE	0	0.006	-9999	-10000	0	0
KLRG1/SHIP	-0.057	0.13	-9999	-0.52	43	43
LCP2	0	0.009	-9999	-0.29	1	1
PLA2G4A	-0.12	0.21	-9999	-0.5	208	208
RASA1	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.094	0.2	-9999	-0.47	216	216
IKK complex	0.019	0.093	-9999	-0.23	50	50
WIPF1	0	0	-9999	-10000	0	0

×

PDGFR-alpha signaling pathway

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
PDGFRA	-0.052	0.2	-9999	-0.81	74	74
PDGF/PDGFRA/CRKL	-0.041	0.15	-9999	-0.61	73	73
positive regulation of JUN kinase activity	-0.031	0.12	-9999	-0.46	73	73
CRKL	0	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.044	0.15	-9999	-0.61	73	73
AP1	-0.36	0.53	-9999	-1.2	325	325
mol:IP3	-0.035	0.16	-9999	-0.63	73	73
PLCG1	-0.035	0.16	-9999	-0.63	73	73
PDGF/PDGFRA/alphaV Integrin	-0.041	0.15	-9999	-0.61	73	73
RAPGEF1	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
mol:Ca2+	-0.035	0.16	-9999	-0.63	73	73
CAV3	-0.001	0.015	-9999	-0.29	3	3
CAV1	-0.17	0.33	-9999	-0.79	238	238
SHC/Grb2/SOS1	-0.031	0.12	-9999	-0.47	73	73
PDGF/PDGFRA/Shf	-0.042	0.15	-9999	-0.61	73	73
FOS	-0.32	0.54	-9999	-1.1	325	325
JUN	-0.024	0.059	-9999	-0.67	7	7
oligodendrocyte development	-0.041	0.15	-9999	-0.6	73	73
GRB2	0	0.009	-9999	-0.29	1	1
PIK3R1	-0.009	0.086	-9999	-0.79	13	13
mol:DAG	-0.035	0.16	-9999	-0.63	73	73
PDGF/PDGFRA	-0.052	0.2	-9999	-0.8	74	74
actin cytoskeleton reorganization	-0.041	0.15	-9999	-0.6	74	74
SRF	0.015	0.022	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
PI3K	-0.041	0.14	-9999	-0.54	83	83
PDGF/PDGFRA/Crk/C3G	-0.035	0.13	-9999	-0.52	73	73
JAK1	-0.025	0.16	-9999	-0.6	74	74
ELK1/SRF	-0.028	0.12	-9999	-0.48	73	73
SHB	-0.001	0.025	-9999	-0.79	1	1
SHF	-0.001	0.027	-9999	-0.79	1	1
CSNK2A1	0.019	0.027	-9999	-10000	0	0
GO:0007205	-0.037	0.17	-9999	-0.65	73	73
SOS1	0	0	-9999	-10000	0	0
Ras protein signal transduction	-0.031	0.12	-9999	-0.46	73	73
PDGF/PDGFRA/SHB	-0.042	0.15	-9999	-0.61	74	74
PDGF/PDGFRA/Caveolin-1	-0.17	0.32	-9999	-0.71	263	263
ITGAV	0	0	-9999	-10000	0	0
ELK1	-0.035	0.16	-9999	-0.59	73	73
PIK3CA	0	0.009	-9999	-0.29	1	1
PDGF/PDGFRA/Crk	-0.041	0.15	-9999	-0.61	73	73
JAK-STAT cascade	-0.025	0.16	-9999	-0.6	74	74
cell proliferation	-0.041	0.15	-9999	-0.61	73	73

×

Ras signaling in the CD4+ TCR pathway

Figure S51. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S51. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.12	0.18	-9999	-0.39	326	326
MAP3K8	0.001	0.073	-9999	-0.74	10	10
FOS	-0.034	0.14	-9999	-0.46	39	39
PRKCA	-0.012	0.13	-9999	-0.77	30	30
PTPN7	-0.009	0.074	-9999	-0.3	64	64
HRAS	-0.002	0.027	-9999	-0.3	9	9
PRKCB	-0.011	0.12	-9999	-0.56	39	39
NRAS	-0.001	0.013	-9999	-0.3	2	2
RAS family/GTP	-0.002	0.015	-9999	-10000	0	0
MAPK3	-0.007	0.073	-9999	-0.25	34	34
MAP2K1	-0.013	0.14	-9999	-0.6	47	47
ELK1	-0.003	0.01	-9999	-0.29	1	1
BRAF	-0.032	0.12	-9999	-0.57	47	47
mol:GTP	-0.002	0.003	-9999	-0.006	325	325
MAPK1	-0.007	0.073	-9999	-0.28	2	2
RAF1	-0.032	0.12	-9999	-0.57	47	47
KRAS	-0.001	0.013	-9999	-0.29	2	2

×

PLK1 signaling events

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
regulation of centriole-centriole cohesion	0.029	0.031	-9999	-10000	0	0
BUB1B	-0.041	0.053	-9999	-10000	0	0
PLK1	-0.008	0.024	-9999	-10000	0	0
PLK1S1	0	0.014	-9999	-10000	0	0
KIF2A	0.001	0.022	-9999	-10000	0	0
regulation of mitotic centrosome separation	-0.008	0.024	-9999	-10000	0	0
GOLGA2	0	0	-9999	-10000	0	0
Hec1/SPC24	-0.17	0.12	-9999	-0.28	529	529
WEE1	-0.002	0.024	-9999	-10000	0	0
cytokinesis	-0.056	0.058	-9999	-0.27	12	12
PP2A-alpha B56	0.027	0.019	-9999	-10000	0	0
AURKA	-0.001	0.015	-9999	-10000	0	0
PICH/PLK1	-0.073	0.098	-9999	-0.34	11	11
CENPE	-0.05	0.086	-9999	-0.19	17	17
RhoA/GTP	0	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.001	0.022	-9999	-10000	0	0
PPP2CA	0	0	-9999	-10000	0	0
FZR1	0	0	-9999	-10000	0	0
TPX2	-0.006	0.017	-9999	-10000	0	0
PAK1	-0.006	0.043	-9999	-0.29	25	25
SPC24	-0.18	0.14	-9999	-0.29	680	680
FBXW11	0	0	-9999	-10000	0	0
CLSPN	-0.006	0.019	-9999	-10000	0	0
GORASP1	0	0	-9999	-10000	0	0
metaphase	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NLP	-0.005	0.014	-9999	-0.052	2	2
G2 phase of mitotic cell cycle	-0.001	0.002	-9999	-10000	0	0
STAG2	-0.001	0.024	-9999	-0.79	1	1
GRASP65/GM130/RAB1/GTP	0.008	0.009	-9999	-10000	0	0
spindle elongation	-0.008	0.024	-9999	-10000	0	0
ODF2	0.002	0.004	-9999	-10000	0	0
BUB1	0.02	0.015	-9999	-10000	0	0
TPT1	0	0.014	-9999	-10000	0	0
CDC25C	-0.009	0.017	-9999	-10000	0	0
CDC25B	0.005	0.041	-9999	-0.29	20	20
SGOL1	-0.03	0.031	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
CCNB1/CDK1	-0.021	0.044	-9999	-10000	0	0
CDC14B	-0.01	0.11	-9999	-0.62	35	35
CDC20	-0.16	0.15	-9999	-0.29	588	588
PLK1/PBIP1	-0.029	0.053	-9999	-0.18	6	6
mitosis	-0.006	0.007	-9999	-0.022	2	2
FBXO5	0	0.023	-9999	-10000	0	0
CDC2	-0.001	0.002	-9999	-10000	0	0
NDC80	-0.18	0.14	-9999	-0.29	660	660
metaphase plate congression	-0.002	0.016	-9999	-10000	0	0
ERCC6L	-0.064	0.09	-9999	-10000	0	0
NLP/gamma Tubulin	-0.001	0.014	-9999	-10000	0	0
microtubule cytoskeleton organization	0	0.014	-9999	-10000	0	0
G2/M transition DNA damage checkpoint	-0.001	0.001	-9999	-10000	0	0
PPP1R12A	0	0	-9999	-10000	0	0
interphase	-0.001	0.001	-9999	-10000	0	0
PLK1/PRC1-2	-0.14	0.1	-9999	-0.29	275	275
GRASP65/GM130/RAB1/GTP/PLK1	-0.002	0.004	-9999	-10000	0	0
RAB1A	0	0	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
Aurora A/BORA	-0.003	0.024	-9999	-0.17	2	2
mitotic prometaphase	-0.002	0.001	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.014	0.05	-9999	-0.29	30	30
microtubule-based process	-0.12	0.069	-9999	-0.19	23	23
Golgi organization	-0.008	0.024	-9999	-10000	0	0
Cohesin/SA2	-0.01	0.018	-9999	-0.45	1	1
PPP1CB/MYPT1	0	0	-9999	-10000	0	0
KIF20A	-0.22	0.13	-9999	-0.29	819	819
APC/C/CDC20	-0.088	0.081	-9999	-0.17	423	423
PPP2R1A	0	0	-9999	-10000	0	0
chromosome segregation	-0.029	0.053	-9999	-0.18	6	6
PRC1	-0.074	0.13	-9999	-0.29	276	276
ECT2	-0.004	0.039	-9999	-0.2	4	4
C13orf34	-0.001	0.022	-9999	-0.17	2	2
NUDC	-0.002	0.016	-9999	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.041	0.052	-9999	-10000	0	0
spindle assembly	-0.004	0.02	-9999	-10000	0	0
spindle stabilization	0	0.014	-9999	-10000	0	0
APC/C/HCDH1	-0.017	0.093	-9999	-0.53	35	35
MKLP2/PLK1	-0.12	0.069	-9999	-0.19	23	23
CCNB1	-0.05	0.12	-9999	-0.29	221	221
PPP1CB	0	0	-9999	-10000	0	0
BTRC	0	0	-9999	-10000	0	0
ROCK2	-0.009	0.088	-9999	-0.51	31	31
TUBG1	0	0.014	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.024	0.041	-9999	-10000	0	0
MLF1IP	-0.026	0.074	-9999	-0.2	158	158
INCENP	0.002	0.004	-9999	-10000	0	0

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.003	0.048	-9999	-0.79	4	4
alphaV beta3 Integrin	-0.022	0.11	-9999	-0.6	38	38
PTK2	-0.067	0.19	-9999	-0.56	123	123
positive regulation of JNK cascade	-0.039	0.11	-9999	-0.34	123	123
CDC42/GDP	-0.002	0.16	-9999	-0.46	123	123
Rac1/GDP	0	0.16	-9999	-0.45	123	123
RAP1B	0	0	-9999	-10000	0	0
RAP1A	0	0	-9999	-10000	0	0
CTNNB1	0	0	-9999	-10000	0	0
CDC42/GTP	-0.048	0.13	-9999	-0.42	123	123
nectin-3/I-afadin	-0.07	0.2	-9999	-0.62	123	123
RAPGEF1	-0.01	0.18	-9999	-0.52	123	123
mol:GTP	0	0	-9999	-10000	0	0
CRK	-0.025	0.21	-9999	-0.61	123	123
PDGFB-D/PDGFRB	-0.003	0.048	-9999	-0.79	4	4
TLN1	0.001	0.1	-9999	-0.54	13	13
Rap1/GTP	-0.041	0.11	-9999	-0.36	123	123
IQGAP1	0	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	-0.003	0.036	-9999	-0.48	6	6
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.07	0.2	-9999	-0.62	123	123
PVR	0	0.009	-9999	-0.29	1	1
Necl-5(dimer)	0	0.009	-9999	-0.29	1	1
mol:GDP	-0.014	0.2	-9999	-0.57	123	123
MLLT4	-0.005	0.059	-9999	-0.72	7	7
PIK3CA	0	0.009	-9999	-0.29	1	1
PI3K	-0.058	0.17	-9999	-0.49	129	129
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.003	0.045	-9999	-0.6	6	6
positive regulation of lamellipodium assembly	-0.04	0.11	-9999	-0.35	123	123
PVRL1	0	0	-9999	-10000	0	0
PVRL3	-0.088	0.25	-9999	-0.79	122	122
PVRL2	-0.001	0.015	-9999	-0.29	3	3
PIK3R1	-0.009	0.086	-9999	-0.79	13	13
CDH1	-0.022	0.13	-9999	-0.79	30	30
CLDN1	-0.037	0.16	-9999	-0.59	69	69
JAM-A/CLDN1	-0.076	0.19	-9999	-0.52	154	154
SRC	-0.079	0.22	-9999	-0.69	123	123
ITGB3	-0.029	0.15	-9999	-0.74	42	42
nectin-1(dimer)/I-afadin/I-afadin	-0.003	0.045	-9999	-0.6	6	6
FARP2	-0.019	0.2	-9999	-0.56	123	123
RAC1	0	0	-9999	-10000	0	0
CTNNA1	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.061	0.17	-9999	-0.54	123	123
nectin-1/I-afadin	-0.003	0.045	-9999	-0.6	6	6
nectin-2/I-afadin	-0.004	0.046	-9999	-0.6	6	6
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	-0.061	0.17	-9999	-0.54	123	123
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.039	0.11	-9999	-0.34	123	123
alphaV/beta3 Integrin/Talin	-0.041	0.13	-9999	-0.58	43	43
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.004	0.046	-9999	-0.6	6	6
nectin-2(dimer)/I-afadin/I-afadin	-0.004	0.046	-9999	-0.6	6	6
PIP5K1C	-0.033	0.1	-9999	-0.56	14	14
VAV2	-0.02	0.2	-9999	-0.58	123	123
RAP1/GDP	-0.048	0.13	-9999	-0.42	123	123
ITGAV	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.061	0.17	-9999	-0.54	123	123
nectin-3(dimer)/I-afadin/I-afadin	-0.07	0.2	-9999	-0.62	123	123
Rac1/GTP	-0.05	0.14	-9999	-0.44	123	123
PTPRM	-0.037	0.11	-9999	-0.32	127	127
E-cadherin/beta catenin/alpha catenin	-0.014	0.076	-9999	-0.43	35	35
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.005	0.054	-10000	0	-0.55	10	10
HDAC1	0.002	0.008	-10000	0	-10000	0	0
AES	0.001	0.004	-10000	0	-10000	0	0
FBXW11	0	0	-10000	0	-10000	0	0
DTX1	-0.069	0.22	-10000	0	-0.79	96	96
LRP6/FZD1	0	0.006	-10000	0	-10000	0	0
TLE1	-0.005	0.068	-10000	0	-0.79	8	8
AP1	-0.11	0.17	-10000	0	-0.37	328	328
NCSTN	0	0	-10000	0	-10000	0	0
ADAM10	-0.003	0.048	-10000	0	-0.79	4	4
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.008	0.044	-10000	0	-0.34	1	1
NICD/RBPSUH	-0.003	0.042	-10000	0	-0.7	4	4
WIF1	-0.42	0.39	-10000	0	-0.78	583	583
NOTCH1	-0.003	0.045	-10000	0	-0.75	4	4
PSENEN	0	0.009	-10000	0	-0.29	1	1
KREMEN2	-0.14	0.15	-10000	0	-0.29	525	525
DKK1	-0.081	0.19	-10000	0	-0.42	207	207
beta catenin/beta TrCP1	-0.008	0.024	-10000	0	-10000	0	0
APH1B	-0.001	0.024	-10000	0	-0.79	1	1
APH1A	0	0	-10000	0	-10000	0	0
AXIN1	0.003	0.015	-10000	0	-0.21	4	4
CtBP/CBP/TCF1/TLE1/AES	0.003	0.039	-10000	0	-0.33	8	8
PSEN1	0	0	-10000	0	-10000	0	0
FOS	-0.24	0.36	-10000	0	-0.79	325	325
JUN	-0.005	0.063	-10000	0	-0.79	7	7
MAP3K7	0.001	0.01	-10000	0	-0.3	1	1
CTNNB1	-0.002	0.034	0.23	2	-10000	0	2
MAPK3	0	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.085	0.12	-10000	0	-0.61	32	32
HNF1A	-0.001	0.025	-10000	0	-0.29	8	8
CTBP1	0.001	0.004	-10000	0	-10000	0	0
MYC	-0.033	0.22	-10000	0	-1.5	24	24
NKD1	-0.009	0.069	-10000	0	-0.79	6	6
FZD1	0	0	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.041	0.13	-10000	0	-0.44	100	100
apoptosis	-0.11	0.17	-10000	0	-0.36	328	328
Delta 1/NOTCHprecursor	-0.005	0.053	-10000	0	-0.54	10	10
DLL1	-0.004	0.058	-10000	0	-0.79	6	6
PPARD	-0.001	0.013	-10000	0	-10000	0	0
Gamma Secretase	0	0.014	-10000	0	-0.44	1	1
APC	0.003	0.015	-10000	0	-0.21	4	4
DVL1	-0.037	0.035	-10000	0	-10000	0	0
CSNK2A1	0.011	0.003	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.003	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.12	0.14	-10000	0	-0.57	56	56
LRP6	0	0.009	-10000	0	-0.29	1	1
CSNK1A1	0.011	0.003	-10000	0	-10000	0	0
NLK	0.002	0.01	-10000	0	-10000	0	0
CCND1	-0.012	0.094	-10000	0	-1.5	4	4
WNT1	-0.001	0.013	-10000	0	-0.29	2	2
Axin1/APC/beta catenin	0.011	0.037	-10000	0	-10000	0	0
DKK2	-0.024	0.13	-10000	0	-0.76	34	34
NOTCH1 precursor/DVL1	-0.019	0.041	-10000	0	-0.64	4	4
GSK3B	0.001	0.003	-10000	0	-10000	0	0
FRAT1	0.001	0.004	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.041	0.13	-10000	0	-0.44	100	100
PPP2R5D	-0.015	0.037	0.35	6	-10000	0	6
MAPK1	0	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.25	0.23	-10000	0	-0.47	569	569
RBPJ	0	0	-10000	0	-10000	0	0
CREBBP	0.014	0.004	-10000	0	-10000	0	0

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.11	0.2	-10000	0	-0.47	263	263
MAPK9	0.008	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.001	0.022	-10000	0	-0.2	13	13
GNB1/GNG2	-0.006	0.057	-10000	0	-0.53	13	13
GNB1	0	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	0.008	0	-10000	0	-10000	0	0
Gs family/GTP	-0.12	0.21	-10000	0	-0.49	259	259
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	0.027	0.048	0.11	259	-10000	0	259
GNAL	-0.19	0.34	-10000	0	-0.79	259	259
GNG2	-0.009	0.086	-10000	0	-0.79	13	13
CRH	-0.003	0.032	-10000	0	-0.29	13	13
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.005	0.039	-10000	0	-0.45	8	8
MAPK11	0.007	0.024	-10000	0	-0.45	3	3

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	-0.007	0.054	-9999	-0.45	15	15
RGS9BP	-0.019	0.073	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRK1	-0.003	0.029	-9999	-0.29	11	11
mol:Na +	-0.02	0.053	-9999	-10000	0	0
mol:ADP	0.007	0.028	-9999	-10000	0	0
GNAT2	-0.001	0.018	-9999	-0.29	4	4
RGS9-1/Gbeta5/R9AP	-0.062	0.16	-9999	-0.53	107	107
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.001	0.015	-9999	-10000	0	0
GRK7	-0.002	0.027	-9999	-0.29	9	9
CNGB3	-0.01	0.054	-9999	-10000	0	0
Cone Metarhodopsin II/X-Arrestin	-0.001	0.017	-9999	-0.2	8	8
mol:Ca2+	-0.092	0.089	-9999	-10000	0	0
Cone PDE6	-0.054	0.14	-9999	-0.46	107	107
Cone Metarhodopsin II	-0.003	0.019	-9999	-10000	0	0
Na + (4 Units)	-0.098	0.082	-9999	-10000	0	0
GNAT2/GDP	-0.053	0.14	-9999	-0.46	107	107
GNB5	0	0	-9999	-10000	0	0
mol:GMP (4 units)	0.011	0.016	-9999	-10000	0	0
Cone Transducin	-0.008	0.057	-9999	-0.48	15	15
SLC24A2	-0.17	0.14	-9999	-0.29	649	649
GNB3/GNGT2	-0.009	0.071	-9999	-0.6	15	15
GNB3	-0.011	0.088	-9999	-0.63	19	19
GNAT2/GTP	-0.001	0.012	-9999	-0.2	4	4
CNGA3	-0.028	0.086	-9999	-0.29	103	103
ARR3	-0.002	0.025	-9999	-0.29	8	8
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.021	0.053	-9999	-10000	0	0
mol:Pi	-0.062	0.16	-9999	-0.53	107	107
Cone CNG Channel	-0.016	0.04	-9999	-10000	0	0
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.17	0.14	-9999	-0.29	649	649
RGS9	-0.081	0.24	-9999	-0.73	122	122
PDE6C	0	0.009	-9999	-10000	0	0
GNGT2	-0.001	0.034	-9999	-0.79	2	2
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	-0.002	0.022	-9999	-0.29	6	6

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	-0.54	0.37	-9999	-0.79	748	748
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	-0.007	0.045	-9999	-0.29	26	26
TCEB1	-0.001	0.013	-9999	-0.29	2	2
HIF1A/p53	-0.001	0.005	-9999	-10000	0	0
HIF1A	-0.002	0.008	-9999	-10000	0	0
COPS5	0	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	-0.003	0.016	-9999	-10000	0	0
FIH (dimer)	0	0	-9999	-10000	0	0
CDKN2A	-0.052	0.11	-9999	-0.29	192	192
ARNT/IPAS	-0.41	0.28	-9999	-0.6	748	748
HIF1AN	0	0	-9999	-10000	0	0
GNB2L1	0	0	-9999	-10000	0	0
HIF1A/ARNT	-0.001	0.005	-9999	-10000	0	0
CUL2	0	0	-9999	-10000	0	0
OS9	-0.001	0.013	-9999	-0.29	2	2
RACK1/Elongin B/Elongin C	-0.004	0.023	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	-0.001	0.006	-9999	-10000	0	0
PHD1-3/OS9	-0.011	0.038	-9999	-0.47	2	2
HIF1A/RACK1/Elongin B/Elongin C	-0.002	0.015	-9999	-10000	0	0
VHL	0	0	-9999	-10000	0	0
HSP90AA1	0	0.009	-9999	-0.29	1	1
HIF1A/JAB1	-0.001	0.005	-9999	-10000	0	0
EGLN3	-0.022	0.08	-9999	-0.3	81	81
EGLN2	-0.002	0.022	-9999	-0.29	6	6
EGLN1	-0.001	0.024	-9999	-0.79	1	1
TP53	0	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	-0.001	0.005	-9999	-10000	0	0
ARNT	0	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.019	0.04	-9999	-10000	0	0

×

FAS signaling pathway (CD95)

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
SPTAN1	0.011	0.052	0.28	37	-10000	0	37
RFC1	0.011	0.052	0.28	39	-10000	0	39
PRKDC	0.01	0.053	0.28	37	-10000	0	37
RIPK1	0	0.001	-10000	0	-10000	0	0
CASP7	-0.023	0.037	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1	-0.017	0.067	0.25	14	-0.38	17	31
MAP2K4	-0.058	0.16	-10000	0	-0.47	24	24
mol:ceramide	-0.032	0.12	-10000	0	-0.55	21	21
GSN	0.004	0.075	0.28	36	-0.49	13	49
FASLG/FAS/FADD/FAF1/Caspase 8	-0.03	0.072	0.23	14	-0.46	17	31
FAS	0.004	0.055	-10000	0	-0.8	5	5
BID	0.001	0.015	0.32	2	-10000	0	2
MAP3K1	-0.021	0.093	-10000	0	-0.3	11	11
MAP3K7	0.006	0.011	-10000	0	-0.29	1	1
RB1	0.01	0.055	0.28	36	-0.4	2	38
CFLAR	0	0.001	-10000	0	-10000	0	0
HGF/MET	-0.14	0.26	-10000	0	-0.58	256	256
ARHGDIB	0.01	0.053	0.28	37	-10000	0	37
FADD	0.003	0.038	-10000	0	-0.31	16	16
actin filament polymerization	-0.004	0.075	0.49	13	-0.28	36	49
NFKB1	-0.076	0.1	-10000	0	-0.3	13	13
MAPK8	-0.12	0.24	-10000	0	-0.43	402	402
DFFA	0.011	0.052	0.28	38	-10000	0	38
DNA fragmentation during apoptosis	0.011	0.052	0.28	37	-10000	0	37
FAS/FADD/MET	-0.096	0.21	-10000	0	-0.54	190	190
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	-0.002	0.056	-10000	0	-0.33	26	26
FAF1	0.008	0.006	-10000	0	-10000	0	0
PARP1	0.01	0.052	0.28	37	-10000	0	37
DFFB	0.011	0.052	0.28	37	-10000	0	37
CHUK	-0.066	0.088	-10000	0	-10000	0	0
FASLG	-0.015	0.11	-10000	0	-0.43	57	57
FAS/FADD	-0.006	0.05	-10000	0	-0.65	5	5
HGF	-0.053	0.2	-10000	0	-0.78	75	75
LMNA	0.01	0.048	0.26	37	-10000	0	37
CASP6	0.01	0.052	0.28	37	-10000	0	37
CASP10	0.005	0.049	-10000	0	-0.8	4	4
CASP3	0.013	0.063	0.34	39	-10000	0	39
PTPN13	-0.023	0.13	-10000	0	-0.79	32	32
CASP8	0.003	0.023	0.45	2	-10000	0	2
IL6	-0.47	0.67	-10000	0	-1.4	399	399
MET	-0.14	0.3	-10000	0	-0.79	188	188
ICAD/CAD	0.01	0.048	0.26	37	-10000	0	37
FASLG/FAS/FADD/FAF1/Caspase 10	-0.032	0.12	-10000	0	-0.56	21	21
activation of caspase activity by cytochrome c	0.001	0.015	0.32	2	-10000	0	2
PAK2	0.01	0.052	0.28	37	-10000	0	37
BCL2	-0.022	0.14	-10000	0	-0.79	37	37

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.011	0.056	-9999	-0.29	41	41
GPC2	-0.038	0.1	-9999	-0.3	136	136
GPC2/Midkine	-0.031	0.08	-9999	-0.41	17	17
neuron projection morphogenesis	-0.031	0.08	-9999	-0.41	17	17

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	-0.009	0.054	-10000	0	-0.32	31	31
epithelial cell differentiation	-0.012	0.072	-10000	0	-0.44	30	30
CYFIP2	-0.01	0.066	-10000	0	-0.36	31	31
ENAH	0.057	0.058	-10000	0	-10000	0	0
EGFR	-0.3	0.38	-10000	0	-0.78	414	414
EPHA2	-0.004	0.058	-10000	0	-0.79	6	6
MYO6	-0.012	0.069	-10000	0	-0.42	31	31
CTNNB1	0	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.005	0.038	-10000	0	-0.52	4	4
AQP5	-0.23	0.29	-10000	0	-0.58	426	426
CTNND1	0	0.009	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.011	0.067	-10000	0	-0.41	30	30
regulation of calcium-dependent cell-cell adhesion	-0.033	0.11	-10000	0	-0.42	86	86
EGF	-0.16	0.31	-10000	0	-0.78	216	216
NCKAP1	0	0	-10000	0	-10000	0	0
AQP3	-0.038	0.14	-10000	0	-0.59	56	56
cortical microtubule organization	-0.012	0.072	-10000	0	-0.44	30	30
GO:0000145	0.026	0.07	-10000	0	-0.39	30	30
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.012	0.073	-10000	0	-0.45	30	30
MLLT4	-0.005	0.059	-10000	0	-0.72	7	7
ARF6/GDP	-0.012	0.061	-10000	0	-10000	0	0
ARF6	0	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.003	0.036	-10000	0	-0.47	6	6
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.036	0.074	-10000	0	-0.38	30	30
PVRL2	-0.001	0.015	-10000	0	-0.29	3	3
ZYX	-0.012	0.068	-10000	0	-0.42	30	30
ARF6/GTP	-0.003	0.033	-10000	0	-0.43	6	6
CDH1	-0.022	0.13	-10000	0	-0.79	30	30
EGFR/EGFR/EGF/EGF	-0.24	0.26	-10000	0	-0.47	566	566
RhoA/GDP	-0.011	0.067	-10000	0	-0.41	30	30
actin cytoskeleton organization	0.032	0.073	-10000	0	-0.39	31	31
IGF-1R heterotetramer	-0.02	0.12	-10000	0	-0.79	22	22
GIT1	-0.001	0.02	-10000	0	-0.29	5	5
IGF1R	-0.02	0.12	-10000	0	-0.79	22	22
IGF1	-0.18	0.33	-10000	0	-0.79	246	246
DIAPH1	-0.002	0.043	-10000	0	-0.69	4	4
Wnt receptor signaling pathway	0.012	0.072	0.44	30	-10000	0	30
RHOA	0	0	-10000	0	-10000	0	0
RhoA/GTP	-0.012	0.061	-10000	0	-10000	0	0
CTNNA1	0	0	-10000	0	-10000	0	0
VCL	0.033	0.074	-10000	0	-0.4	30	30
EFNA1	0	0.009	-10000	0	-0.29	1	1
LPP	0.03	0.081	-10000	0	-0.39	38	38
Ephrin A1/EPHA2	-0.013	0.071	-10000	0	-0.4	36	36
SEC6/SEC8	-0.012	0.067	-10000	0	-0.75	1	1
MGAT3	-0.034	0.11	-10000	0	-0.42	86	86
HGF/MET	-0.11	0.2	-10000	0	-0.45	264	264
HGF	-0.053	0.2	-10000	0	-0.78	75	75
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.009	0.054	-10000	0	-0.33	31	31
actin cable formation	0.072	0.057	-10000	0	-0.32	1	1
KIAA1543	0.031	0.089	-10000	0	-0.46	31	31
KIFC3	-0.012	0.07	-10000	0	-0.42	32	32
NCK1	0	0	-10000	0	-10000	0	0
EXOC3	0	0	-10000	0	-10000	0	0
ACTN1	-0.012	0.069	-10000	0	-0.42	31	31
NCK1/GIT1	-0.001	0.013	-10000	0	-10000	0	0
mol:GDP	-0.012	0.072	-10000	0	-0.44	30	30
EXOC4	0	0	-10000	0	-10000	0	0
STX4	-0.012	0.068	-10000	0	-0.42	30	30
PIP5K1C	-0.012	0.068	-10000	0	-0.42	30	30
LIMA1	-0.001	0.024	-10000	0	-0.79	1	1
ABI1	0	0	-10000	0	-10000	0	0
ROCK1	-0.01	0.054	-10000	0	-10000	0	0
adherens junction assembly	0.047	0.085	-10000	0	-0.66	6	6
IGF-1R heterotetramer/IGF1	-0.11	0.2	-10000	0	-0.43	280	280
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.004	0.046	-10000	0	-0.6	6	6
MET	-0.14	0.3	-10000	0	-0.79	188	188
PLEKHA7	-0.013	0.078	-10000	0	-0.46	30	30
mol:GTP	-0.003	0.036	-10000	0	-0.47	6	6
establishment of epithelial cell apical/basal polarity	-0.012	0.063	-10000	0	-0.7	1	1
cortical actin cytoskeleton stabilization	-0.009	0.054	-10000	0	-0.32	31	31
regulation of cell-cell adhesion	0.032	0.073	-10000	0	-0.39	31	31
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.009	0.054	-10000	0	-0.33	31	31

×

Signaling events mediated by HDAC Class III

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
EP300	0	0	-10000	0	-10000	0	0
HDAC4	-0.001	0.024	-10000	0	-0.79	1	1
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.012	0.077	0.6	1	-10000	0	1
CDKN1A	-0.002	0.04	-10000	0	-0.94	2	2
KAT2B	-0.001	0.024	-10000	0	-0.79	1	1
BAX	-0.001	0.02	-10000	0	-0.29	5	5
FOXO3	-0.001	0.017	-10000	0	-0.33	3	3
FOXO1	-0.008	0.079	-10000	0	-0.79	11	11
FOXO4	0.022	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0	0	-10000	0	-10000	0	0
TAT	-0.56	0.36	-10000	0	-0.77	787	787
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.01	0.029	-10000	0	-0.6	1	1
PPARGC1A	-0.17	0.32	-10000	0	-0.77	240	240
FHL2	-0.005	0.059	-10000	0	-0.72	7	7
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0	0.007	-10000	0	-10000	0	0
HIST2H4A	-0.012	0.077	-10000	0	-0.6	1	1
SIRT1/FOXO3a	0	0.014	-10000	0	-0.25	3	3
SIRT1	0	0.009	0.21	2	-10000	0	2
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0	0.017	-10000	0	-0.52	1	1
SIRT1/Histone H1b	-0.003	0.012	-10000	0	-10000	0	0
apoptosis	0	0.012	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.11	0.21	-10000	0	-0.53	229	229
p53/SIRT1	0.001	0.019	0.43	2	-10000	0	2
SIRT1/FOXO4	0	0.007	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	-0.007	0.06	-10000	0	-0.48	17	17
HIST1H1E	0.014	0.022	-10000	0	-10000	0	0
SIRT1/p300	0	0.007	-10000	0	-10000	0	0
muscle cell differentiation	0.002	0.023	0.52	1	-10000	0	1
TP53	0	0.009	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0	0.012	-10000	0	-10000	0	0
CREBBP	0	0	-10000	0	-10000	0	0
MEF2D	0	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.42	0.27	-10000	0	-0.6	759	759
ACSS2	0.02	0.02	-10000	0	-0.6	1	1
SIRT1/PCAF/MYOD	-0.002	0.024	-10000	0	-0.52	1	1

×

TCGA08_rtk_signaling

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
PDGFRA	-0.053	0.2	-10000	0	-0.78	74	74
HRAS	-0.002	0.027	-10000	0	-0.29	9	9
EGFR	-0.3	0.38	-10000	0	-0.78	414	414
AKT	0.013	0.081	-10000	0	-0.56	19	19
FOXO3	-0.002	0.041	-10000	0	-0.79	3	3
AKT1	0	0	-10000	0	-10000	0	0
FOXO1	-0.008	0.079	-10000	0	-0.79	11	11
AKT3	-0.014	0.1	-10000	0	-0.79	19	19
FOXO4	0	0	-10000	0	-10000	0	0
MET	-0.14	0.3	-10000	0	-0.79	188	188
PIK3CA	0	0.009	-10000	0	-0.29	1	1
PIK3CB	0	0	-10000	0	-10000	0	0
NRAS	-0.001	0.013	-10000	0	-0.29	2	2
PIK3CG	-0.013	0.096	-10000	0	-0.69	20	20
PIK3R3	0	0.009	-10000	0	-0.29	1	1
PIK3R2	0	0	-10000	0	-10000	0	0
NF1	-0.001	0.024	-10000	0	-0.79	1	1
RAS	-0.097	0.16	0.26	1	-0.37	213	214
ERBB2	-0.024	0.083	-10000	0	-0.3	89	89
proliferation/survival/translation	-0.004	0.058	0.26	13	-10000	0	13
PI3K	-0.088	0.16	-10000	0	-0.36	220	220
PIK3R1	-0.009	0.086	-10000	0	-0.79	13	13
KRAS	-0.001	0.013	-10000	0	-0.29	2	2
FOXO	0.026	0.029	-10000	0	-0.49	1	1
AKT2	0	0	-10000	0	-10000	0	0
PTEN	-0.001	0.034	-10000	0	-0.79	2	2

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	-0.009	0.052	-10000	0	-0.42	13	13
adherens junction organization	0.031	0.064	-10000	0	-0.3	31	31
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.14	0.18	-10000	0	-0.58	24	24
FMN1	0.022	0.093	-10000	0	-0.45	26	26
mol:IP3	-0.009	0.049	-10000	0	-0.39	13	13
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.01	0.053	-10000	0	-0.31	31	31
CTNNB1	0.001	0.004	-10000	0	-10000	0	0
AKT1	-0.01	0.051	-10000	0	-0.38	13	13
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.014	0.082	-10000	0	-0.5	30	30
CTNND1	0.011	0.009	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.033	0.057	-10000	0	-10000	0	0
VASP	0.033	0.058	-10000	0	-10000	0	0
ZYX	0.033	0.058	-10000	0	-10000	0	0
JUB	0.031	0.064	-10000	0	-0.3	35	35
EGFR(dimer)	-0.16	0.21	-10000	0	-0.43	410	410
E-cadherin/beta catenin-gamma catenin	-0.014	0.084	-10000	0	-0.5	31	31
mol:PI-3-4-5-P3	-0.011	0.055	-10000	0	-0.4	13	13
PIK3CA	0.011	0.009	-10000	0	-0.29	1	1
PI3K	-0.011	0.056	-10000	0	-0.41	13	13
FYN	0.04	0.055	-10000	0	-0.38	2	2
mol:Ca2+	-0.009	0.048	-10000	0	-0.38	13	13
JUP	0	0.026	-10000	0	-0.54	2	2
PIK3R1	0.002	0.087	-10000	0	-0.79	13	13
mol:DAG	-0.009	0.049	-10000	0	-0.39	13	13
CDH1	-0.022	0.13	-10000	0	-0.79	30	30
RhoA/GDP	-0.14	0.18	-10000	0	-0.58	24	24
establishment of polarity of embryonic epithelium	0.033	0.057	-10000	0	-10000	0	0
SRC	0	0.009	-10000	0	-0.29	1	1
RAC1	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
EGFR	-0.3	0.38	-10000	0	-0.78	414	414
CASR	0.033	0.055	-10000	0	-0.36	13	13
RhoA/GTP	-0.008	0.044	-10000	0	-0.34	13	13
AKT2	-0.01	0.051	-10000	0	-0.38	13	13
actin cable formation	0.03	0.09	-10000	0	-0.43	25	25
apoptosis	0.01	0.052	0.4	13	-10000	0	13
CTNNA1	0.012	0.002	-10000	0	-10000	0	0
mol:GDP	-0.16	0.2	-10000	0	-0.4	416	416
PIP5K1A	0.033	0.058	-10000	0	-10000	0	0
PLCG1	-0.009	0.051	-10000	0	-0.4	13	13
Rac1/GTP	-0.15	0.19	-10000	0	-0.39	410	410
homophilic cell adhesion	0.001	0.002	-10000	0	-10000	0	0

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0	0.1	-9999	-0.53	40	40
ADCY5	-0.16	0.26	-9999	-0.53	351	351
ADCY6	0.02	0	-9999	-10000	0	0
ADCY7	0.02	0	-9999	-10000	0	0
ADCY1	-0.008	0.098	-9999	-0.53	29	29
ADCY2	-0.032	0.15	-9999	-0.53	90	90
ADCY3	0.02	0.005	-9999	-10000	0	0
ADCY8	0.01	0.028	-9999	-10000	0	0
PRKCE	0.011	0	-9999	-10000	0	0
ADCY9	0.02	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.031	0.1	-9999	-0.31	74	74

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.003	0.041	-9999	-0.2	43	43
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.047	0.13	-9999	-0.6	47	47
STXBP1	-0.005	0.063	-9999	-0.79	7	7
ACh/CHRNA1	-0.063	0.082	-9999	-0.23	26	26
RAB3GAP2/RIMS1/UNC13B	-0.038	0.11	-9999	-0.52	47	47
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	-0.067	0.18	-9999	-0.43	170	170
mol:ACh	0.001	0.031	-9999	-0.15	35	35
RAB3GAP2	0	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.038	0.093	-9999	-0.39	54	54
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.062	0.082	-9999	-0.23	26	26
UNC13B	0	0	-9999	-10000	0	0
CHRNA1	-0.1	0.14	-9999	-0.29	372	372
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.059	0.12	-9999	-0.48	60	60
SNAP25	-0.016	0.067	-9999	-0.37	35	35
VAMP2	0	0	-9999	-10000	0	0
SYT1	-0.088	0.18	-9999	-0.38	253	253
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.009	0.051	-9999	-0.53	7	7
STX1A/SNAP25 fragment 1/VAMP2	-0.038	0.093	-9999	-0.39	54	54

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.001	0.017	-10000	0	-0.29	3	3
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.035	0.13	0.44	34	-10000	0	34
IL27/IL27R/JAK1	-0.074	0.19	-10000	0	-0.62	61	61
TBX21	-0.043	0.21	-10000	0	-0.59	85	85
IL12B	-0.056	0.12	-10000	0	-0.29	230	230
IL12A	-0.028	0.14	-10000	0	-0.52	79	79
IL6ST	-0.091	0.27	-10000	0	-0.8	136	136
IL27RA/JAK1	-0.008	0.073	-10000	0	-1.1	4	4
IL27	-0.025	0.095	-10000	0	-0.3	120	120
TYK2	0.01	0.006	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.12	0.18	-10000	0	-10000	0	0
T-helper 2 cell differentiation	0.035	0.13	0.44	34	-10000	0	34
T cell proliferation during immune response	0.035	0.13	0.44	34	-10000	0	34
MAPKKK cascade	-0.035	0.13	-10000	0	-0.44	34	34
STAT3	0	0	-10000	0	-10000	0	0
STAT2	0	0	-10000	0	-10000	0	0
STAT1	-0.004	0.039	-10000	0	-0.3	19	19
IL12RB1	-0.005	0.067	-10000	0	-0.32	43	43
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.059	0.23	-10000	0	-0.62	100	100
IL27/IL27R/JAK2/TYK2	-0.035	0.13	-10000	0	-0.45	33	33
positive regulation of T cell mediated cytotoxicity	-0.035	0.13	-10000	0	-0.44	34	34
STAT1 (dimer)	-0.093	0.22	0.46	21	-0.72	62	83
JAK2	0.005	0.025	-10000	0	-0.79	1	1
JAK1	0	0.024	-10000	0	-0.79	1	1
STAT2 (dimer)	-0.044	0.11	-10000	0	-0.45	23	23
T cell proliferation	-0.18	0.25	-10000	0	-0.46	415	415
IL12/IL12R/TYK2/JAK2	0.011	0.07	-10000	0	-10000	0	0
IL17A	-0.12	0.18	-10000	0	-10000	0	0
mast cell activation	0.035	0.13	0.44	34	-10000	0	34
IFNG	-0.001	0.025	-10000	0	-0.077	11	11
T cell differentiation	-0.004	0.006	-10000	0	-0.019	23	23
STAT3 (dimer)	-0.044	0.11	-10000	0	-0.46	22	22
STAT5A (dimer)	-0.048	0.12	-10000	0	-0.47	31	31
STAT4 (dimer)	-0.062	0.14	-10000	0	-0.49	67	67
STAT4	-0.032	0.16	-10000	0	-0.78	45	45
T cell activation	-0.009	0.009	0.13	3	-10000	0	3
IL27R/JAK2/TYK2	-0.062	0.17	-10000	0	-0.61	30	30
GATA3	-0.039	0.28	-10000	0	-1.4	40	40
IL18	0.007	0.031	-10000	0	-10000	0	0
positive regulation of mast cell cytokine production	-0.044	0.11	-10000	0	-0.45	23	23
IL27/EBI3	-0.026	0.083	-10000	0	-0.53	13	13
IL27RA	-0.001	0.079	-10000	0	-1.4	3	3
IL6	-0.29	0.38	-10000	0	-0.79	399	399
STAT5A	-0.006	0.067	-10000	0	-0.79	8	8
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	0.004	0.03	0.48	3	-10000	0	3
IL1B	0.001	0.076	-10000	0	-0.53	20	20
EBI3	-0.004	0.075	-10000	0	-0.5	20	20
TNF	-0.001	0.074	-10000	0	-0.61	13	13

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.035	0.12	-10000	0	-0.58	41	41
FYN	0.016	0.18	-10000	0	-0.7	48	48
LAT/GRAP2/SLP76	-0.029	0.14	-10000	0	-0.62	47	47
IKBKB	-0.001	0.013	-10000	0	-0.29	2	2
AKT1	0.03	0.12	-10000	0	-0.45	48	48
B2M	0.011	0.004	-10000	0	-10000	0	0
IKBKG	-0.008	0.026	-10000	0	-0.14	14	14
MAP3K8	-0.007	0.072	-10000	0	-0.74	10	10
mol:Ca2+	-0.024	0.047	-10000	0	-0.12	213	213
integrin-mediated signaling pathway	-0.002	0.028	-10000	0	-0.52	3	3
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.021	0.17	-10000	0	-0.67	50	50
TRPV6	-0.16	0.32	-10000	0	-0.77	226	226
CD28	0.002	0.074	-10000	0	-0.53	17	17
SHC1	0.011	0.18	-10000	0	-0.72	48	48
receptor internalization	-0.001	0.2	-10000	0	-0.62	75	75
PRF1	0	0.22	-10000	0	-1.1	36	36
KRAS	-0.001	0.013	-10000	0	-0.29	2	2
GRB2	0	0.009	-10000	0	-0.29	1	1
COT/AKT1	0.031	0.1	-10000	0	-0.37	49	49
LAT	0.009	0.18	-10000	0	-0.71	51	51
EntrezGene:6955	0.001	0.003	-10000	0	-10000	0	0
CD3D	-0.023	0.14	-10000	0	-0.48	77	77
CD3E	-0.017	0.13	-10000	0	-0.5	62	62
CD3G	-0.032	0.17	-10000	0	-0.56	83	83
RASGRP2	0.003	0.041	-10000	0	-0.18	45	45
RASGRP1	0.036	0.12	-10000	0	-0.46	47	47
HLA-A	0.009	0.031	-10000	0	-0.29	11	11
RASSF5	-0.002	0.042	-10000	0	-0.66	4	4
RAP1A/GTP/RAPL	-0.002	0.028	-10000	0	-0.53	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.033	0.043	-10000	0	-0.12	40	40
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.014	0.047	-10000	0	-0.23	35	35
PRKCA	-0.013	0.084	-10000	0	-0.31	59	59
GRAP2	-0.014	0.1	-10000	0	-0.72	22	22
mol:IP3	0.019	0.15	0.27	183	-0.44	44	227
EntrezGene:6957	0.001	0.003	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.006	0.2	-10000	0	-0.81	47	47
ORAI1	0.078	0.15	0.38	212	-10000	0	212
CSK	0.009	0.18	-10000	0	-0.65	59	59
B7 family/CD28	-0.027	0.18	-10000	0	-0.65	61	61
CHUK	0	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.002	0.22	-10000	0	-0.73	65	65
PTPN6	0.008	0.18	-10000	0	-0.65	59	59
VAV1	0.01	0.18	-10000	0	-0.63	64	64
Monovalent TCR/CD3	-0.024	0.2	-10000	0	-0.66	72	72
CBL	0	0	-10000	0	-10000	0	0
LCK	0.01	0.19	-10000	0	-0.67	60	60
PAG1	0.008	0.18	-10000	0	-0.66	59	59
RAP1A	0	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.001	0.21	-10000	0	-0.73	63	63
CD80	-0.069	0.13	-10000	0	-0.29	285	285
CD86	0.008	0.023	-10000	0	-0.3	6	6
PDK1/CARD11/BCL10/MALT1	-0.018	0.058	-10000	0	-0.27	37	37
HRAS	-0.002	0.027	-10000	0	-0.29	9	9
GO:0035030	-0.001	0.15	-10000	0	-0.53	61	61
CD8A	0	0.074	-10000	0	-0.37	34	34
CD8B	-0.021	0.15	-10000	0	-0.55	66	66
PTPRC	-0.001	0.075	-10000	0	-0.5	19	19
PDK1/PKC theta	0.033	0.15	-10000	0	-0.57	51	51
CSK/PAG1	0.014	0.18	-10000	0	-0.73	45	45
SOS1	0	0	-10000	0	-10000	0	0
peptide-MHC class I	-0.002	0.018	-10000	0	-10000	0	0
GRAP2/SLP76	-0.035	0.17	-10000	0	-0.7	51	51
STIM1	0.041	0.078	-10000	0	-10000	0	0
RAS family/GTP	0.041	0.054	-10000	0	-0.17	34	34
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.005	0.22	-10000	0	-0.68	75	75
mol:DAG	-0.008	0.1	-10000	0	-0.4	44	44
RAP1A/GDP	0.015	0.018	-10000	0	-10000	0	0
PLCG1	0.001	0.003	-10000	0	-10000	0	0
CD247	-0.008	0.12	-10000	0	-0.58	37	37
cytotoxic T cell degranulation	0.002	0.21	-10000	0	-0.95	39	39
RAP1A/GTP	-0.003	0.013	-10000	0	-0.067	33	33
mol:PI-3-4-5-P3	0.026	0.14	-10000	0	-0.53	50	50
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.012	0.18	0.29	171	-0.6	44	215
NRAS	-0.001	0.013	-10000	0	-0.29	2	2
ZAP70	-0.031	0.12	-10000	0	-0.79	20	20
GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.026	0.14	-10000	0	-0.6	47	47
MALT1	0	0	-10000	0	-10000	0	0
TRAF6	0	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.031	0.13	-10000	0	-0.57	53	53
CARD11	-0.007	0.051	-10000	0	-0.34	21	21
PRKCB	-0.012	0.085	-10000	0	-0.32	54	54
PRKCE	-0.006	0.069	-10000	0	-0.28	38	38
PRKCQ	0.024	0.18	-10000	0	-0.65	53	53
LCP2	0	0.009	-10000	0	-0.29	1	1
BCL10	0	0	-10000	0	-10000	0	0
regulation of survival gene product expression	0.032	0.1	-10000	0	-0.37	48	48
IKK complex	0.041	0.045	-10000	0	-0.12	29	29
RAS family/GDP	-0.002	0.006	-10000	0	-10000	0	0
MAP3K14	0.036	0.081	-10000	0	-0.29	39	39
PDPK1	0.033	0.12	-10000	0	-0.43	45	45
TCR/CD3/MHC I/CD8/Fyn	-0.005	0.23	-10000	0	-0.9	52	52

×

Canonical Wnt 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
HDAC1	0.004	0.018	-10000	0	-10000	0	0
AES	0.004	0.015	-10000	0	-10000	0	0
FBXW11	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0	0.006	-10000	0	-10000	0	0
SMAD4	-0.001	0.024	-10000	0	-0.79	1	1
DKK2	-0.024	0.13	-10000	0	-0.76	34	34
TLE1	-0.002	0.069	-10000	0	-0.79	8	8
MACF1	0.007	0.006	-10000	0	-10000	0	0
CTNNB1	0.1	0.087	-10000	0	-10000	0	0
WIF1	-0.42	0.39	-10000	0	-0.78	583	583
beta catenin/RanBP3	0.014	0.078	0.38	43	-10000	0	43
KREMEN2	-0.14	0.15	-10000	0	-0.29	525	525
DKK1	-0.081	0.19	-10000	0	-0.42	207	207
beta catenin/beta TrCP1	0.1	0.083	-10000	0	-10000	0	0
FZD1	0	0.002	-10000	0	-10000	0	0
AXIN2	-0.014	0.21	-10000	0	-1.6	20	20
AXIN1	0.007	0.006	-10000	0	-10000	0	0
RAN	0.001	0.003	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.007	0.024	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.093	0.077	0.3	1	-0.49	6	7
Axin1/APC/GSK3	0.001	0.014	0.24	1	-10000	0	1
Axin1/APC/GSK3/beta catenin/Macf1	0.077	0.033	-10000	0	-10000	0	0
HNF1A	0.002	0.029	-10000	0	-0.29	7	7
CTBP1	0.004	0.016	-10000	0	-10000	0	0
MYC	-0.019	0.23	-10000	0	-1.5	25	25
RANBP3	0.001	0.003	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.084	0.12	-10000	0	-0.61	32	32
NKD1	-0.009	0.069	-10000	0	-0.79	6	6
TCF4	-0.004	0.08	-10000	0	-0.78	11	11
TCF3	0.004	0.017	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0	0.006	-10000	0	-10000	0	0
Ran/GTP	0	0.001	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.014	0.099	0.45	45	-0.42	1	46
LEF1	-0.033	0.1	-10000	0	-0.3	132	132
DVL1	0.072	0.065	-10000	0	-10000	0	0
CSNK2A1	0	0.002	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.099	0.089	-10000	0	-0.58	5	5
DKK1/LRP6/Kremen 2	-0.12	0.14	-10000	0	-0.57	56	56
LRP6	0	0.009	-10000	0	-0.29	1	1
CSNK1A1	0.004	0.018	-10000	0	-10000	0	0
NLK	0.011	0.014	-10000	0	-0.3	2	2
CCND1	0.001	0.11	-10000	0	-1.6	4	4
WNT1	0.005	0.014	-10000	0	-0.29	2	2
GSK3A	0.009	0.006	-10000	0	-10000	0	0
GSK3B	0	0.001	-10000	0	-10000	0	0
FRAT1	0	0	-10000	0	-10000	0	0
PPP2R5D	0.044	0.045	0.36	6	-10000	0	6
APC	0.001	0.009	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.14	0.13	0.27	569	-10000	0	569
CREBBP	0.004	0.016	-10000	0	-10000	0	0

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.003	0.036	-9999	-10000	0	0
Syndecan-4/Syndesmos	-0.025	0.037	-9999	-0.63	1	1
positive regulation of JNK cascade	-0.051	0.1	-9999	-0.46	7	7
Syndecan-4/ADAM12	-0.033	0.055	-9999	-0.54	2	2
CCL5	-0.015	0.079	-9999	-0.36	44	44
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0	0	-9999	-10000	0	0
ITGA5	0	0.009	-9999	-0.29	1	1
SDCBP	0	0	-9999	-10000	0	0
PLG	-0.001	0.026	-9999	-0.29	8	8
ADAM12	-0.019	0.077	-9999	-0.31	68	68
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	-0.001	0.02	-9999	-0.29	5	5
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.054	0.044	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.072	0.13	-9999	-0.46	62	62
Syndecan-4/CXCL12/CXCR4	-0.053	0.11	-9999	-0.48	7	7
Syndecan-4/Laminin alpha3	-0.13	0.19	-9999	-0.48	204	204
MDK	-0.011	0.056	-9999	-0.29	41	41
Syndecan-4/FZD7	-0.033	0.068	-9999	-0.46	14	14
Syndecan-4/Midkine	-0.028	0.042	-9999	-0.63	1	1
FZD7	-0.016	0.11	-9999	-0.79	22	22
Syndecan-4/FGFR1/FGF	-0.19	0.21	-9999	-0.48	167	167
THBS1	-0.004	0.053	-9999	-0.79	5	5
integrin-mediated signaling pathway	-0.035	0.072	-9999	-0.47	14	14
positive regulation of MAPKKK cascade	-0.051	0.1	-9999	-0.46	7	7
Syndecan-4/TACI	-0.036	0.067	-9999	-0.5	7	7
CXCR4	-0.007	0.045	-9999	-10000	0	0
cell adhesion	-0.02	0.061	-9999	-0.34	28	28
Syndecan-4/Dynamin	-0.024	0.036	-9999	-0.63	1	1
Syndecan-4/TSP1	-0.026	0.046	-9999	-0.48	5	5
Syndecan-4/GIPC	-0.024	0.037	-9999	-0.63	1	1
Syndecan-4/RANTES	-0.031	0.053	-9999	-0.5	5	5
ITGB1	0	0	-9999	-10000	0	0
LAMA1	-0.09	0.25	-9999	-0.77	127	127
LAMA3	-0.2	0.34	-9999	-0.79	276	276
RAC1	0	0	-9999	-10000	0	0
PRKCA	0.004	0.12	-9999	-0.73	29	29
Syndecan-4/alpha-Actinin	-0.025	0.039	-9999	-0.54	2	2
TFPI	-0.039	0.17	-9999	-0.79	54	54
F2	0	0.034	-9999	-0.29	14	14
alpha5/beta1 Integrin	0	0.006	-9999	-10000	0	0
positive regulation of cell adhesion	-0.16	0.23	-9999	-0.55	154	154
ACTN1	-0.001	0.024	-9999	-0.79	1	1
TNC	-0.022	0.12	-9999	-0.79	26	26
Syndecan-4/CXCL12	-0.056	0.11	-9999	-0.46	40	40
FGF6	-0.001	0.034	-9999	-0.79	2	2
RHOA	0	0	-9999	-10000	0	0
CXCL12	-0.061	0.21	-9999	-0.79	84	84
TNFRSF13B	-0.028	0.11	-9999	-0.39	77	77
FGF2	-0.32	0.39	-9999	-0.79	444	444
FGFR1	-0.009	0.08	-9999	-0.68	14	14
Syndecan-4/PI-4-5-P2	-0.018	0.048	-9999	-0.64	1	1
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.11	0.15	-9999	-0.3	432	432
cell migration	-0.024	0.019	-9999	-10000	0	0
PRKCD	0.005	0.014	-9999	-0.29	1	1
vasculogenesis	-0.026	0.044	-9999	-0.46	5	5
SDC4	-0.019	0.051	-9999	-0.68	1	1
Syndecan-4/Tenascin C	-0.036	0.076	-9999	-0.52	8	8
Syndecan-4/PI-4-5-P2/PKC alpha	-0.043	0.035	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.024	0.036	-9999	-0.63	1	1
MMP9	-0.12	0.15	-9999	-0.29	484	484
Rac1/GTP	-0.028	0.057	-9999	-0.34	28	28
cytoskeleton organization	-0.025	0.035	-9999	-0.6	1	1
GIPC1	-0.001	0.015	-9999	-0.29	3	3
Syndecan-4/TFPI	-0.045	0.097	-9999	-0.48	22	22

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.005	0.13	-10000	0	-0.4	55	55
TBX21	-0.014	0.34	-10000	0	-1.2	60	60
B2M	0.011	0.005	-10000	0	-10000	0	0
TYK2	0.017	0.015	-10000	0	-10000	0	0
IL12RB1	0.004	0.072	-10000	0	-0.33	38	38
GADD45B	0.031	0.22	-10000	0	-0.83	32	32
IL12RB2	-0.057	0.19	-10000	0	-0.43	185	185
GADD45G	0.02	0.22	-10000	0	-0.81	36	36
natural killer cell activation	0.007	0.018	-10000	0	-10000	0	0
RELB	-0.003	0.028	-10000	0	-0.29	10	10
RELA	0	0	-10000	0	-10000	0	0
IL18	0.008	0.045	-10000	0	-0.29	24	24
IL2RA	-0.031	0.12	-10000	0	-0.38	87	87
IFNG	-0.04	0.1	-10000	0	-0.29	150	150
STAT3 (dimer)	0.023	0.22	-10000	0	-0.64	61	61
HLA-DRB5	-0.018	0.096	-10000	0	-0.33	85	85
FASLG	0.001	0.29	-10000	0	-1.1	49	49
NF kappa B2 p52/RelB	-0.08	0.2	-10000	0	-0.73	69	69
CD4	0.009	0.006	-10000	0	-10000	0	0
SOCS1	-0.005	0.043	-10000	0	-0.32	18	18
EntrezGene:6955	-0.006	0.014	-10000	0	-10000	0	0
CD3D	-0.026	0.14	-10000	0	-0.49	77	77
CD3E	-0.02	0.13	-10000	0	-0.5	62	62
CD3G	-0.035	0.17	-10000	0	-0.57	83	83
IL12Rbeta2/JAK2	-0.026	0.15	-10000	0	-0.59	55	55
CCL3	0.011	0.26	-10000	0	-0.98	40	40
CCL4	0.013	0.26	-10000	0	-0.92	42	42
HLA-A	0.008	0.032	-10000	0	-0.3	11	11
IL18/IL18R	0.021	0.14	-10000	0	-0.54	55	55
NOS2	0.017	0.25	-10000	0	-0.9	44	44
IL12/IL12R/TYK2/JAK2/SPHK2	-0.004	0.13	-10000	0	-0.39	60	60
IL1R1	-0.002	0.31	-10000	0	-1.2	50	50
IL4	-0.005	0.018	-10000	0	-10000	0	0
JAK2	0.016	0.03	-10000	0	-0.82	1	1
EntrezGene:6957	-0.005	0.013	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.032	0.25	-10000	0	-1	50	50
RAB7A	0.045	0.2	-10000	0	-0.74	25	25
lysosomal transport	0.046	0.19	-10000	0	-0.7	25	25
FOS	-0.35	0.66	-10000	0	-1.3	336	336
STAT4 (dimer)	0.019	0.26	-10000	0	-0.86	57	57
STAT5A (dimer)	-0.087	0.22	-10000	0	-0.7	83	83
GZMA	0.002	0.28	-10000	0	-0.99	49	49
GZMB	-0.013	0.31	-10000	0	-1.1	55	55
HLX	-0.001	0.015	-10000	0	-0.29	3	3
LCK	0.002	0.29	-10000	0	-0.82	76	76
TCR/CD3/MHC II/CD4	-0.065	0.19	-10000	0	-0.53	93	93
IL2/IL2R	-0.031	0.1	-10000	0	-0.48	41	41
MAPK14	0.034	0.22	-10000	0	-0.78	43	43
CCR5	0.024	0.22	-10000	0	-0.87	32	32
IL1B	0.004	0.1	-10000	0	-0.7	20	20
STAT6	0.025	0.087	-10000	0	-0.25	13	13
STAT4	-0.032	0.16	-10000	0	-0.78	45	45
STAT3	0	0	-10000	0	-10000	0	0
STAT1	-0.005	0.038	-10000	0	-0.29	19	19
NFKB1	0	0	-10000	0	-10000	0	0
NFKB2	0	0.009	-10000	0	-0.29	1	1
IL12B	-0.048	0.12	-10000	0	-0.29	230	230
CD8A	0	0.074	-10000	0	-0.37	34	34
CD8B	-0.022	0.15	-10000	0	-0.55	66	66
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.005	0.13	0.39	55	-10000	0	55
IL2RB	-0.012	0.064	-10000	0	-0.32	42	42
proteasomal ubiquitin-dependent protein catabolic process	0.026	0.24	-10000	0	-0.77	57	57
IL2RG	-0.017	0.086	-10000	0	-0.36	53	53
IL12	-0.054	0.16	-10000	0	-0.59	68	68
STAT5A	-0.006	0.067	-10000	0	-0.79	8	8
CD247	-0.011	0.12	-10000	0	-0.58	37	37
IL2	-0.002	0.025	-10000	0	-0.29	8	8
SPHK2	0	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.034	0.19	-10000	0	-0.68	79	79
IL12/IL12R/TYK2/JAK2	0.006	0.29	-10000	0	-0.82	74	74
MAP2K3	0.03	0.22	-10000	0	-0.79	41	41
RIPK2	-0.001	0.02	-10000	0	-0.29	5	5
MAP2K6	0.025	0.23	-10000	0	-0.77	48	48
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.008	0.026	-10000	0	-0.54	2	2
IL18RAP	-0.015	0.15	-10000	0	-0.73	43	43
IL12Rbeta1/TYK2	0.014	0.056	-10000	0	-0.64	2	2
EOMES	-0.024	0.18	-10000	0	-1.5	17	17
STAT1 (dimer)	0.026	0.22	-10000	0	-0.66	51	51
T cell proliferation	0.031	0.2	-10000	0	-0.62	55	55
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0	0.11	-10000	0	-0.79	19	19
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.063	0.17	-10000	0	-0.75	45	45
ATF2	0.041	0.21	-10000	0	-0.72	42	42

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	-0.002	0.032	-10000	0	-0.79	1	1
SVIL	-0.005	0.057	-10000	0	-0.79	5	5
ZNF318	0.022	0.057	-10000	0	-10000	0	0
JMJD2C	-0.003	0.041	-10000	0	-0.12	106	106
T-DHT/AR/Ubc9	-0.082	0.18	-10000	0	-0.54	146	146
CARM1	0	0	-10000	0	-10000	0	0
PRDX1	0.003	0.012	-10000	0	-0.29	1	1
PELP1	0.005	0.012	-10000	0	-10000	0	0
CTNNB1	0.001	0.015	-10000	0	-10000	0	0
AKT1	0.007	0.018	-10000	0	-10000	0	0
PTK2B	0.001	0.013	-10000	0	-10000	0	0
MED1	0.002	0.047	-10000	0	-0.29	20	20
MAK	0.012	0.1	0.26	1	-0.55	20	21
response to oxidative stress	0.001	0.004	-10000	0	-10000	0	0
HIP1	-0.005	0.061	-10000	0	-0.79	6	6
GSN	-0.011	0.088	-10000	0	-0.79	13	13
NCOA2	-0.038	0.17	-10000	0	-0.79	53	53
NCOA6	-0.001	0.02	-10000	0	-0.29	1	1
DNA-PK	0.022	0.058	-10000	0	-10000	0	0
NCOA4	0	0	-10000	0	-10000	0	0
PIAS3	0.001	0.015	-10000	0	-10000	0	0
cell proliferation	-0.008	0.11	-10000	0	-0.88	11	11
XRCC5	0.006	0.015	-10000	0	-10000	0	0
UBE3A	-0.005	0.031	-10000	0	-10000	0	0
T-DHT/AR/SNURF	-0.095	0.21	-10000	0	-0.58	162	162
FHL2	-0.019	0.12	-10000	0	-1.2	6	6
RANBP9	0	0.018	-10000	0	-10000	0	0
JMJD1A	-0.01	0.055	-10000	0	-0.14	151	151
CDK6	-0.008	0.09	-10000	0	-0.73	16	16
TGFB1I1	-0.003	0.046	-10000	0	-0.79	3	3
T-DHT/AR/CyclinD1	-0.094	0.19	-10000	0	-0.54	154	154
XRCC6	0.006	0.015	-10000	0	-10000	0	0
T-DHT/AR	-0.067	0.21	-10000	0	-0.53	162	162
CTDSP1	0.004	0.005	-10000	0	-10000	0	0
CTDSP2	0.015	0.039	-10000	0	-10000	0	0
BRCA1	-0.002	0.034	-10000	0	-0.49	3	3
TCF4	0.004	0.085	-10000	0	-0.78	11	11
CDKN2A	-0.043	0.11	-10000	0	-0.29	169	169
SRF	0.024	0.019	-10000	0	-10000	0	0
NKX3-1	-0.081	0.19	-10000	0	-1.2	21	21
KLK3	-0.18	0.5	-10000	0	-1.5	128	128
TMF1	0.004	0.005	-10000	0	-10000	0	0
HNRNPA1	0.009	0.021	-10000	0	-10000	0	0
AOF2	-0.008	0.023	-10000	0	-0.072	128	128
APPL1	0.034	0.032	-10000	0	-10000	0	0
T-DHT/AR/Caspase 8	-0.074	0.19	-10000	0	-0.54	146	146
AR	-0.1	0.28	-10000	0	-0.8	147	147
UBA3	0.004	0.005	-10000	0	-10000	0	0
PATZ1	0.009	0.021	-10000	0	-10000	0	0
PAWR	0.003	0.025	-10000	0	-0.79	1	1
PRKDC	0.005	0.024	-10000	0	-0.29	4	4
PA2G4	0.011	0.028	-10000	0	-10000	0	0
UBE2I	0	0	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.069	0.17	-10000	0	-0.5	146	146
RPS6KA3	-0.007	0.07	-10000	0	-0.79	8	8
T-DHT/AR/ARA70	-0.086	0.18	-10000	0	-0.54	147	147
LATS2	0.009	0.023	-10000	0	-10000	0	0
T-DHT/AR/PRX1	-0.065	0.18	0.19	1	-0.5	146	147
Cyclin D3/CDK11 p58	0	0.006	-10000	0	-10000	0	0
VAV3	-0.01	0.076	-10000	0	-0.43	26	26
KLK2	-0.12	0.32	-10000	0	-1.2	79	79
CASP8	0.004	0.011	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.099	0.2	-10000	0	-0.54	180	180
TMPRSS2	-0.17	0.39	-10000	0	-1.2	135	135
CCND1	-0.016	0.074	-10000	0	-0.34	46	46
PIAS1	-0.005	0.031	-10000	0	-10000	0	0
mol:T-DHT	-0.008	0.033	-10000	0	-0.078	181	181
CDC2L1	0.001	0.002	-10000	0	-10000	0	0
PIAS4	-0.011	0.049	-10000	0	-10000	0	0
T-DHT/AR/CDK6	-0.085	0.2	-10000	0	-0.54	160	160
CMTM2	0.003	0.013	-10000	0	-0.29	1	1
SNURF	-0.021	0.13	-10000	0	-0.79	29	29
ZMIZ1	0.004	0.03	-10000	0	-0.36	1	1
CCND3	0.002	0.01	-10000	0	-10000	0	0
TGIF1	0.009	0.021	-10000	0	-10000	0	0
FKBP4	-0.003	0.033	-10000	0	-0.3	9	9

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.13	0.22	-9999	-0.46	300	300
TC10/GTP	-0.11	0.18	-9999	-0.41	284	284
Insulin Receptor/Insulin/IRS1/Shp2	-0.02	0.097	-9999	-0.49	45	45
HRAS	-0.002	0.027	-9999	-0.29	9	9
APS homodimer	-0.014	0.062	-9999	-0.29	52	52
GRB14	-0.1	0.22	-9999	-0.47	230	230
FOXO3	-0.014	0.065	-9999	-0.68	9	9
AKT1	-0.057	0.12	-9999	-0.51	11	11
INSR	0.012	0.009	-9999	-0.29	1	1
Insulin Receptor/Insulin	-0.003	0.026	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0	0	-9999	-10000	0	0
SORBS1	-0.21	0.35	-9999	-0.79	284	284
CRK	0	0	-9999	-10000	0	0
PTPN1	0.033	0.03	-9999	-10000	0	0
CAV1	-0.098	0.24	-9999	-0.51	256	256
CBL/APS/CAP/Crk-II/C3G	-0.12	0.2	-9999	-0.45	284	284
Insulin Receptor/Insulin/IRS1/NCK2	-0.02	0.097	-9999	-0.49	45	45
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.023	0.096	-9999	-0.43	58	58
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	-0.012	0.055	-9999	-10000	0	0
RPS6KB1	-0.008	0.13	-9999	-0.46	11	11
PARD6A	-0.002	0.023	-9999	-0.29	7	7
CBL	0	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0.002	-9999	-10000	0	0
PIK3R1	-0.009	0.086	-9999	-0.79	13	13
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.05	0.11	-9999	-0.48	11	11
HRAS/GTP	-0.016	0.073	-9999	-0.47	2	2
Insulin Receptor	0.012	0.009	-9999	-0.29	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.019	0.09	-9999	-0.45	45	45
PRKCI	-0.013	0.032	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.062	0.14	-9999	-0.4	140	140
SHC1	0	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0	0.002	-9999	-10000	0	0
PI3K	-0.023	0.097	-9999	-0.43	58	58
NCK2	0	0	-9999	-10000	0	0
RHOQ	0	0	-9999	-10000	0	0
mol:H2O2	0	0.003	-9999	-10000	0	0
HRAS/GDP	-0.002	0.018	-9999	-10000	0	0
AKT2	-0.057	0.12	-9999	-0.51	11	11
PRKCZ	-0.014	0.036	-9999	-0.6	1	1
SH2B2	-0.014	0.062	-9999	-0.29	52	52
SHC/SHIP	-0.018	0.085	-9999	-0.43	45	45
F2RL2	-0.06	0.15	-9999	-0.36	185	185
TRIP10	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	0	0.004	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0	0.004	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	-0.13	0.21	-9999	-0.48	284	284
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0	0.003	-9999	-10000	0	0
INPP5D	0.007	0.096	-9999	-0.46	45	45
SOS1	0	0	-9999	-10000	0	0
SGK1	-0.009	0.073	-9999	-0.98	6	6
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
IRS1	-0.033	0.16	-9999	-0.79	45	45
p62DOK/RasGAP	0	0.002	-9999	-10000	0	0
INS	0.003	0.004	-9999	-10000	0	0
mol:PI-3-4-P2	0.007	0.095	-9999	-0.45	45	45
GRB2	0	0.009	-9999	-0.29	1	1
EIF4EBP1	-0.014	0.14	-9999	-0.46	25	25
PTPRA	0.012	0.003	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-0.29	1	1
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	-0.013	0.064	-9999	-0.32	45	45
Insulin Receptor/Insulin/IRS1	-0.021	0.099	-9999	-0.5	45	45
Insulin Receptor/Insulin/IRS3	-0.001	0.007	-9999	-10000	0	0
Par3/Par6	-0.027	0.074	-9999	-0.45	23	23

×

Regulation of Androgen receptor activity

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.021	0.003	-9999	-10000	0	0
SMARCC1	0.005	0.019	-9999	-0.55	1	1
REL	-0.005	0.087	-9999	-0.79	13	13
HDAC7	0.009	0.13	-9999	-0.58	18	18
JUN	0	0.064	-9999	-0.79	7	7
EP300	0	0	-9999	-10000	0	0
KAT2B	-0.001	0.024	-9999	-0.79	1	1
KAT5	0.002	0.005	-9999	-10000	0	0
MAPK14	0.006	0.096	-9999	-0.61	25	25
FOXO1	-0.008	0.079	-9999	-0.79	11	11
T-DHT/AR	-0.004	0.14	-9999	-0.52	34	34
MAP2K6	-0.01	0.12	-9999	-0.78	26	26
BRM/BAF57	-0.001	0.011	-9999	-10000	0	0
MAP2K4	0.008	0.025	-9999	-0.8	1	1
SMARCA2	0.004	0.006	-9999	-10000	0	0
PDE9A	-0.087	0.29	-9999	-1.2	62	62
NCOA2	-0.032	0.17	-9999	-0.79	53	53
CEBPA	-0.004	0.072	-9999	-0.79	9	9
EHMT2	0.005	0.006	-9999	-10000	0	0
cell proliferation	0.015	0.14	-9999	-0.47	32	32
NR0B1	-0.01	0.057	-9999	-0.31	36	36
EGR1	-0.25	0.37	-9999	-0.79	345	345
RXRs/9cRA	-0.12	0.21	-9999	-0.48	265	265
AR/RACK1/Src	-0.004	0.11	-9999	-0.48	33	33
AR/GR	-0.054	0.13	-9999	-0.43	63	63
GNB2L1	0.001	0.004	-9999	-10000	0	0
PKN1	0	0.009	-9999	-0.29	1	1
RCHY1	0	0	-9999	-10000	0	0
epidermal growth factor receptor activity	-0.001	0.003	-9999	-10000	0	0
MAPK8	0.015	0.058	-9999	-0.61	9	9
T-DHT/AR/TIF2/CARM1	-0.018	0.16	-9999	-0.58	46	46
SRC	0.021	0.093	-9999	-0.46	33	33
NR3C1	-0.011	0.092	-9999	-0.79	15	15
KLK3	-0.2	0.41	-9999	-1.2	151	151
APPBP2	0.008	0.017	-9999	-0.29	3	3
TRIM24	0.005	0.006	-9999	-10000	0	0
T-DHT/AR/TIP60	-0.027	0.098	-9999	-0.51	33	33
TMPRSS2	-0.16	0.41	-9999	-1.2	137	137
RXRG	-0.19	0.34	-9999	-0.78	268	268
mol:9cRA	-0.001	0.002	-9999	-10000	0	0
RXRA	0	0	-9999	-10000	0	0
RXRB	0	0	-9999	-10000	0	0
CARM1	0.007	0.006	-9999	-10000	0	0
NR2C2	-0.008	0.079	-9999	-0.79	11	11
KLK2	-0.043	0.24	-9999	-0.74	99	99
AR	-0.028	0.14	-9999	-0.34	171	171
SENP1	0	0	-9999	-10000	0	0
HSP90AA1	0	0.009	-9999	-0.29	1	1
MDM2	0.004	0.024	-9999	-0.29	5	5
SRY	0.003	0.01	-9999	-10000	0	0
GATA2	-0.024	0.13	-9999	-0.62	42	42
MYST2	0.002	0.01	-9999	-0.29	1	1
HOXB13	-0.14	0.15	-9999	-0.3	502	502
T-DHT/AR/RACK1/Src	-0.014	0.1	-9999	-0.49	33	33
positive regulation of transcription	-0.024	0.13	-9999	-0.62	42	42
DNAJA1	0.009	0.006	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.006	0.013	-9999	-10000	0	0
NCOA1	0.012	0.026	-9999	-0.82	1	1
SPDEF	-0.058	0.2	-9999	-0.75	80	80
T-DHT/AR/TIF2	0.011	0.1	-9999	-0.44	27	27
T-DHT/AR/Hsp90	-0.034	0.094	-9999	-0.51	33	33
GSK3B	0.008	0.006	-9999	-10000	0	0
NR2C1	0.003	0.006	-9999	-10000	0	0
mol:T-DHT	0.014	0.098	-9999	-0.5	33	33
SIRT1	0	0	-9999	-10000	0	0
ZMIZ2	0.005	0.013	-9999	-10000	0	0
POU2F1	0.021	0.026	-9999	-0.43	1	1
T-DHT/AR/DAX-1	-0.036	0.099	-9999	-0.52	34	34
CREBBP	0	0	-9999	-10000	0	0
SMARCE1	0.003	0.017	-9999	-0.3	3	3

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.055	0.12	-9999	-0.57	6	6
RAD9A	0	0.009	-9999	-0.29	1	1
AP1	-0.18	0.28	-9999	-0.61	326	326
IFNAR2	0.011	0.005	-9999	-10000	0	0
AKT1	-0.037	0.11	-9999	-0.28	167	167
ER alpha/Oestrogen	-0.12	0.22	-9999	-0.61	167	167
NFX1/SIN3/HDAC complex	0.025	0.025	-9999	-10000	0	0
EGF	-0.15	0.32	-9999	-0.78	216	216
SMG5	0	0	-9999	-10000	0	0
SMG6	0	0	-9999	-10000	0	0
SP3/HDAC2	0	0	-9999	-10000	0	0
TERT/c-Abl	-0.067	0.089	-9999	-0.53	6	6
SAP18	0.006	0.006	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	-0.14	0.15	-9999	-0.29	553	553
WRN	0	0	-9999	-10000	0	0
SP1	0.012	0.005	-9999	-10000	0	0
SP3	0.009	0.005	-9999	-10000	0	0
TERF2IP	0	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.052	0.078	-9999	-0.52	4	4
Mad/Max	0	0.006	-9999	-10000	0	0
TERT	-0.056	0.12	-9999	-0.58	6	6
CCND1	-0.048	0.13	-9999	-1.3	4	4
MAX	0.009	0.005	-9999	-10000	0	0
RBBP7	0.004	0.026	-9999	-0.29	8	8
RBBP4	0.005	0.025	-9999	-0.79	1	1
TERF2	0	0	-9999	-10000	0	0
PTGES3	0	0	-9999	-10000	0	0
SIN3A	0.006	0.006	-9999	-10000	0	0
Telomerase/911	0.012	0.024	-9999	-10000	0	0
CDKN1B	0.009	0.074	-9999	-0.87	3	3
RAD1	0	0	-9999	-10000	0	0
XRCC5	0	0	-9999	-10000	0	0
XRCC6	0	0	-9999	-10000	0	0
SAP30	0.005	0.019	-9999	-0.29	4	4
TRF2/PARP2	0	0	-9999	-10000	0	0
UBE3A	0.009	0.005	-9999	-10000	0	0
JUN	0.002	0.064	-9999	-0.79	7	7
E6	0	0.001	-9999	-10000	0	0
HPV-16 E6/E6AP	0	0	-9999	-10000	0	0
FOS	-0.23	0.36	-9999	-0.79	325	325
IFN-gamma/IRF1	-0.025	0.063	-9999	-0.36	5	5
PARP2	0	0	-9999	-10000	0	0
BLM	-0.03	0.089	-9999	-0.29	113	113
Telomerase	-0.006	0.028	-9999	-10000	0	0
IRF1	0.011	0.02	-9999	-0.28	3	3
ESR1	-0.15	0.29	-9999	-0.58	291	291
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0.007	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0	0.007	-9999	-10000	0	0
HDAC1	0.006	0.006	-9999	-10000	0	0
HDAC2	0.011	0.005	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.021	0.011	-9999	-10000	0	0
ABL1	0	0	-9999	-10000	0	0
MXD1	0.009	0.01	-9999	-0.29	1	1
MRE11A	0	0	-9999	-10000	0	0
HUS1	0	0	-9999	-10000	0	0
RPS6KB1	-0.001	0.015	-9999	-0.29	3	3
TERT/NF kappa B1/14-3-3	-0.066	0.1	-9999	-0.62	4	4
NR2F2	0.001	0.042	-9999	-0.79	3	3
MAPK3	0.014	0.019	-9999	-10000	0	0
MAPK1	0.014	0.019	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.001	0.016	-9999	-0.29	3	3
NFKB1	0	0	-9999	-10000	0	0
HNRNPC	0	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	0	-9999	-10000	0	0
EGFR	-0.29	0.38	-9999	-0.78	414	414
mol:Oestrogen	0	0.001	-9999	-10000	0	0
EGF/EGFR	-0.34	0.35	-9999	-0.66	555	555
MYC	-0.008	0.12	-9999	-0.79	24	24
IL2	0.004	0.026	-9999	-0.29	8	8
KU	0	0	-9999	-10000	0	0
RAD50	0	0	-9999	-10000	0	0
HSP90AA1	0	0.009	-9999	-0.29	1	1
TGFB1	0.001	0.016	-9999	-0.29	3	3
TRF2/BLM	-0.017	0.051	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.063	0.087	-9999	-0.55	5	5
SP1/HDAC2	0	0	-9999	-10000	0	0
PINX1	0	0	-9999	-10000	0	0
Telomerase/EST1A	-0.052	0.078	-9999	-0.52	4	4
Smad3/Myc	-0.012	0.076	-9999	-0.52	24	24
911 complex	0	0.004	-9999	-10000	0	0
IFNG	-0.03	0.1	-9999	-0.28	150	150
Telomerase/PinX1	-0.052	0.078	-9999	-0.52	4	4
Telomerase/AKT1/mTOR/p70S6K	0.002	0.055	-9999	-10000	0	0
SIN3B	0.006	0.006	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
Telomerase/EST1B	-0.052	0.078	-9999	-0.52	4	4
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	-0.052	0.078	-9999	-0.52	4	4
E2F1	-0.086	0.14	-9999	-0.29	348	348
ZNFX1	0.006	0.006	-9999	-10000	0	0
PIF1	-0.06	0.12	-9999	-0.29	224	224
NCL	0	0	-9999	-10000	0	0
DKC1	-0.001	0.013	-9999	-0.29	2	2
telomeric DNA binding	0	0	-9999	-10000	0	0

×

Osteopontin-mediated 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.037	0.085	-9999	-0.44	38	38
NF kappa B1 p50/RelA/I kappa B alpha	-0.024	0.07	-9999	-0.46	6	6
alphaV/beta3 Integrin/Osteopontin/Src	-0.046	0.076	-9999	-10000	0	0
AP1	-0.14	0.21	-9999	-0.78	38	38
ILK	-0.007	0.11	-9999	-0.47	38	38
bone resorption	-0.038	0.11	-9999	-0.66	21	21
PTK2B	0	0	-9999	-10000	0	0
PYK2/p130Cas	0.003	0.09	-9999	-0.42	38	38
ITGAV	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.018	0.1	-9999	-0.6	31	31
alphaV/beta3 Integrin/Osteopontin	-0.051	0.11	-9999	-0.52	38	38
MAP3K1	-0.008	0.11	-9999	-0.48	38	38
JUN	-0.005	0.063	-9999	-0.79	7	7
MAPK3	0.008	0.11	-9999	-0.43	38	38
MAPK1	0.008	0.11	-9999	-0.43	38	38
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
MAPK8	0.002	0.13	-9999	-0.52	40	40
ITGB3	-0.028	0.14	-9999	-0.74	42	42
NFKBIA	0.022	0.1	-9999	-0.42	38	38
FOS	-0.24	0.36	-9999	-0.79	325	325
CD44	-0.001	0.015	-9999	-0.29	3	3
CHUK	0	0	-9999	-10000	0	0
PLAU	0.02	0.1	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.023	0.066	-9999	-0.44	6	6
BCAR1	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.021	0.11	-9999	-0.59	38	38
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.008	0.11	-9999	-0.47	38	38
VAV3	-0.003	0.11	-9999	-0.44	45	45
MAP3K14	-0.005	0.11	-9999	-0.47	38	38
ROCK2	-0.022	0.13	-9999	-0.79	31	31
SPP1	-0.075	0.12	-9999	-0.28	288	288
RAC1	0	0	-9999	-10000	0	0
Rac1/GTP	-0.036	0.084	-9999	-0.4	45	45
MMP2	-0.073	0.21	-9999	-0.68	38	38

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.018	0.12	-9999	-0.77	26	26
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	-0.001	0.024	-9999	-0.79	1	1
RAC1-CDC42/GTP/PAK family	-0.12	0.14	-9999	-0.27	489	489
response to UV	0	0	-9999	-10000	0	0
YES1	-0.001	0.024	-9999	-0.79	1	1
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0	0	-9999	-10000	0	0
FYN	-0.001	0.034	-9999	-0.79	2	2
MAP3K12	0	0	-9999	-10000	0	0
FGR	-0.001	0.025	-9999	-0.54	2	2
p38 alpha/TAB1	-0.007	0.033	-9999	-0.32	4	4
PRKG1	-0.053	0.2	-9999	-0.79	73	73
DUSP8	-0.002	0.042	-9999	-0.66	4	4
PGK/cGMP/p38 alpha	-0.032	0.1	-9999	-0.39	76	76
apoptosis	-0.007	0.032	-9999	-0.33	3	3
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0	0	-9999	-10000	0	0
DUSP1	-0.1	0.26	-9999	-0.79	141	141
PAK1	-0.007	0.044	-9999	-0.29	25	25
SRC	0	0.009	-9999	-0.29	1	1
RAC1/OSM/MEKK3/MKK3	0	0.006	-9999	-10000	0	0
TRAF6	0	0	-9999	-10000	0	0
RAC1	0	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	-0.001	0.013	-9999	-0.29	2	2
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.018	0.069	-9999	-0.34	21	21
BLK	-0.044	0.11	-9999	-0.3	159	159
HCK	-0.004	0.033	-9999	-10000	0	0
MAP2K3	0	0.009	-9999	-0.29	1	1
DUSP16	0	0	-9999	-10000	0	0
DUSP10	-0.001	0.015	-9999	-0.29	3	3
TRAF6/MEKK3	0	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.029	0.048	-9999	-0.34	4	4
positive regulation of innate immune response	0.024	0.074	-9999	-0.36	21	21
LCK	-0.02	0.1	-9999	-0.41	54	54
p38alpha-beta/MKP7	-0.012	0.054	-9999	-0.34	20	20
p38alpha-beta/MKP5	-0.012	0.055	-9999	-0.34	20	20
PGK/cGMP	-0.041	0.15	-9999	-0.61	73	73
PAK2	0	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.058	0.13	-9999	-0.37	157	157
CDC42	0	0	-9999	-10000	0	0
RALB	0	0	-9999	-10000	0	0
RALA	0	0	-9999	-10000	0	0
PAK3	-0.35	0.39	-9999	-0.79	489	489

×

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	-0.003	0.063	-10000	0	-0.66	9	9
CDKN2C	0.006	0.038	-10000	0	-0.78	2	2
CDKN2A	-0.054	0.12	-10000	0	-0.31	192	192
CCND2	0.007	0.033	0.24	8	-0.16	12	20
RB1	-0.008	0.032	0.19	4	-0.25	8	12
CDK4	0.01	0.03	0.25	9	-10000	0	9
CDK6	0.007	0.038	0.27	8	-0.22	13	21
G1/S progression	-0.006	0.036	0.25	8	-0.19	4	12

×

Syndecan-2-mediated signaling events

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
Syndecan-2/Fibronectin	-0.06	0.076	-9999	-0.41	6	6
EPHB2	-0.005	0.038	-9999	-0.29	19	19
Syndecan-2/TACI	-0.018	0.074	-9999	-0.52	18	18
LAMA1	-0.09	0.25	-9999	-0.77	127	127
Syndecan-2/alpha2 ITGB1	-0.12	0.21	-9999	-0.46	292	292
HRAS	-0.002	0.027	-9999	-0.29	9	9
Syndecan-2/CASK	-0.002	0.029	-9999	-0.52	3	3
ITGA5	0	0.009	-9999	-0.29	1	1
BAX	0.034	0.056	-9999	-0.64	3	3
EPB41	0	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.002	0.026	-9999	-0.47	3	3
LAMA3	-0.2	0.34	-9999	-0.79	276	276
EZR	-0.001	0.015	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.11	0.27	-9999	-0.79	147	147
Syndecan-2/MMP2	-0.007	0.069	-9999	-0.65	11	11
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.015	0.095	-9999	-0.6	28	28
dendrite morphogenesis	-0.005	0.034	-9999	-0.51	3	3
Syndecan-2/GM-CSF	-0.005	0.036	-9999	-0.52	3	3
determination of left/right symmetry	0.017	0.035	-9999	-0.36	7	7
Syndecan-2/PKC delta	-0.002	0.029	-9999	-0.52	3	3
GNB2L1	0	0	-9999	-10000	0	0
MAPK3	0.022	0.036	-9999	-0.47	3	3
MAPK1	0.022	0.036	-9999	-0.47	3	3
Syndecan-2/RACK1	-0.003	0.027	-9999	-0.44	3	3
NF1	-0.001	0.024	-9999	-0.79	1	1
FGFR/FGF/Syndecan-2	0.017	0.035	-9999	-0.36	7	7
ITGA2	-0.02	0.12	-9999	-0.79	28	28
MAPK8	0.028	0.059	-9999	-0.54	11	11
Syndecan-2/alpha2/beta1 Integrin	-0.063	0.17	-9999	-0.5	136	136
Syndecan-2/Kininogen	-0.005	0.035	-9999	-0.52	3	3
ITGB1	0	0	-9999	-10000	0	0
SRC	-0.002	0.025	-9999	-0.42	3	3
Syndecan-2/CASK/Protein 4.1	-0.002	0.026	-9999	-0.48	3	3
extracellular matrix organization	-0.002	0.029	-9999	-0.51	3	3
actin cytoskeleton reorganization	-0.06	0.076	-9999	-0.41	6	6
Syndecan-2/Caveolin-2/Ras	-0.066	0.17	-9999	-0.48	147	147
Syndecan-2/Laminin alpha3	-0.13	0.23	-9999	-0.52	279	279
Syndecan-2/RasGAP	-0.002	0.025	-9999	-0.42	3	3
alpha5/beta1 Integrin	0	0.006	-9999	-10000	0	0
PRKCD	0	0.009	-9999	-0.29	1	1
Syndecan-2 dimer	-0.005	0.034	-9999	-0.52	3	3
GO:0007205	0	0.002	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	-0.002	0.023	-9999	-0.4	3	3
RHOA	0	0	-9999	-10000	0	0
SDCBP	0	0	-9999	-10000	0	0
TNFRSF13B	-0.028	0.11	-9999	-0.39	77	77
RASA1	0	0	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.015	0.095	-9999	-0.6	28	28
Syndecan-2/Synbindin	-0.002	0.028	-9999	-0.52	3	3
TGFB1	-0.001	0.015	-9999	-0.29	3	3
CASP3	0.03	0.028	-9999	-0.46	3	3
FN1	-0.12	0.14	-9999	-0.29	432	432
Syndecan-2/IL8	-0.021	0.084	-9999	-0.52	25	25
SDC2	0.017	0.035	-9999	-0.36	7	7
KNG1	-0.006	0.041	-9999	-0.29	22	22
Syndecan-2/Neurofibromin	-0.002	0.032	-9999	-0.52	4	4
TRAPPC4	0	0	-9999	-10000	0	0
CSF2	-0.007	0.044	-9999	-0.29	25	25
Syndecan-2/TGFB1	-0.002	0.029	-9999	-0.52	3	3
Syndecan-2/Syntenin/PI-4-5-P2	-0.002	0.026	-9999	-0.48	3	3
Syndecan-2/Ezrin	-0.002	0.026	-9999	-0.47	3	3
PRKACA	0.03	0.032	-9999	-0.47	4	4
angiogenesis	-0.021	0.084	-9999	-0.52	25	25
MMP2	-0.008	0.079	-9999	-0.75	12	12
IL8	-0.033	0.13	-9999	-0.79	22	22
calcineurin-NFAT signaling pathway	-0.017	0.074	-9999	-0.52	18	18

×

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	0.008	0.044	-9999	-0.79	2	2
ELF1	-0.012	0.051	-9999	-0.38	16	16
CCNA2	-0.11	0.14	-9999	-0.29	426	426
PIK3CA	0.012	0.009	-9999	-0.29	1	1
JAK3	0.008	0.034	-9999	-0.29	14	14
PIK3R1	0.002	0.087	-9999	-0.79	13	13
JAK1	0.011	0.024	-9999	-0.79	1	1
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.057	0.08	-9999	-0.58	9	9
SHC1	0.012	0.001	-9999	-10000	0	0
SP1	-0.005	0.041	-9999	-0.38	13	13
IL2RA	0.001	0.13	-9999	-1	16	16
IL2RB	-0.001	0.066	-9999	-0.32	42	42
SOS1	0.012	0.001	-9999	-10000	0	0
IL2RG	-0.006	0.088	-9999	-0.36	53	53
G1/S transition of mitotic cell cycle	0.004	0.13	-9999	-0.81	23	23
PTPN11	0.012	0.001	-9999	-10000	0	0
CCND2	0.017	0.11	-9999	-1	13	13
LCK	-0.009	0.1	-9999	-0.41	54	54
GRB2	0.011	0.009	-9999	-0.29	1	1
IL2	0.004	0.026	-9999	-0.29	8	8
CDK6	-0.011	0.09	-9999	-0.73	16	16
CCND3	0.063	0.071	-9999	-0.58	5	5

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	0.004	0.11	-10000	0	-0.44	36	36
IKBKB	0.016	0.053	-10000	0	-0.26	3	3
AKT1	0.002	0.082	0.24	2	-0.27	25	27
IKBKG	0.018	0.055	-10000	0	-0.24	10	10
CALM1	-0.011	0.092	-10000	0	-0.45	30	30
PIK3CA	0	0.009	-10000	0	-0.29	1	1
MAP3K1	-0.01	0.15	-10000	0	-0.63	35	35
MAP3K7	0	0.009	-10000	0	-0.29	1	1
mol:Ca2+	-0.02	0.097	0.24	1	-0.48	30	31
DOK1	-0.001	0.018	-10000	0	-10000	0	0
AP-1	-0.04	0.11	-10000	0	-0.26	70	70
LYN	0	0.001	-10000	0	-10000	0	0
BLNK	0	0	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
BCR complex	-0.079	0.21	-10000	0	-0.62	119	119
CD22	-0.061	0.18	-10000	0	-0.54	100	100
CAMK2G	-0.002	0.086	-10000	0	-0.41	30	30
CSNK2A1	0	0	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.047	0.13	-10000	0	-0.76	16	16
GO:0007205	-0.02	0.098	0.24	1	-0.49	30	31
SYK	0	0.009	-10000	0	-0.29	1	1
ELK1	-0.011	0.093	-10000	0	-0.46	30	30
NFATC1	-0.018	0.13	-10000	0	-0.57	34	34
B-cell antigen/BCR complex	-0.079	0.21	-10000	0	-0.62	119	119
PAG1/CSK	-0.001	0.013	-10000	0	-10000	0	0
NFKBIB	0.015	0.02	0.085	1	-10000	0	1
HRAS	-0.009	0.1	-10000	0	-0.47	31	31
NFKBIA	0.016	0.02	0.085	1	-10000	0	1
NF-kappa-B/RelA/I kappa B beta	0.019	0.016	-10000	0	-10000	0	0
RasGAP/Csk	-0.058	0.16	-10000	0	-0.51	100	100
mol:GDP	-0.02	0.091	0.22	1	-0.46	30	31
PTEN	-0.001	0.034	-10000	0	-0.79	2	2
CD79B	-0.028	0.14	-10000	0	-0.58	52	52
NF-kappa-B/RelA/I kappa B alpha	0.019	0.016	-10000	0	-10000	0	0
GRB2	0	0.009	-10000	0	-0.29	1	1
PI3K/BCAP/CD19	-0.028	0.16	-10000	0	-0.47	100	100
PIK3R1	-0.009	0.086	-10000	0	-0.79	13	13
mol:IP3	-0.029	0.097	0.24	1	-0.5	30	31
CSK	0	0	-10000	0	-10000	0	0
FOS	-0.13	0.22	-10000	0	-0.44	345	345
CHUK	0.018	0.055	-10000	0	-0.24	18	18
IBTK	0	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.023	0.077	-10000	0	-0.48	18	18
PTPN6	-0.057	0.16	-10000	0	-0.72	41	41
RELA	0	0	-10000	0	-10000	0	0
BCL2A1	0.015	0.02	-10000	0	-0.12	1	1
VAV2	-0.071	0.16	-10000	0	-0.8	33	33
ubiquitin-dependent protein catabolic process	0.019	0.019	0.088	1	-10000	0	1
BTK	-0.004	0.005	-10000	0	-10000	0	0
CD19	-0.082	0.17	-10000	0	-0.53	97	97
MAP4K1	-0.015	0.07	-10000	0	-0.31	53	53
CD72	-0.009	0.054	-10000	0	-0.79	1	1
PAG1	-0.001	0.02	-10000	0	-0.29	5	5
MAPK14	0.002	0.13	-10000	0	-0.54	31	31
SH3BP5	-0.001	0.024	-10000	0	-0.79	1	1
PIK3AP1	-0.01	0.11	0.27	1	-0.53	30	31
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.042	0.13	-10000	0	-0.47	85	85
RAF1	0	0.096	-10000	0	-0.44	29	29
RasGAP/p62DOK/SHIP	-0.055	0.15	-10000	0	-0.49	100	100
CD79A	-0.083	0.22	-10000	0	-0.54	170	170
re-entry into mitotic cell cycle	-0.04	0.11	-10000	0	-0.26	68	68
RASA1	0	0	-10000	0	-10000	0	0
MAPK3	0.016	0.082	-10000	0	-0.42	17	17
MAPK1	0.016	0.082	-10000	0	-0.42	17	17
CD72/SHP1	-0.055	0.15	-10000	0	-0.68	41	41
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	-0.001	0.13	-10000	0	-0.52	39	39
actin cytoskeleton organization	-0.027	0.15	-10000	0	-0.65	33	33
NF-kappa-B/RelA	0.042	0.033	0.17	1	-10000	0	1
Calcineurin	-0.02	0.071	-10000	0	-0.44	17	17
PI3K	-0.06	0.13	-10000	0	-0.53	44	44
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.031	0.11	0.27	1	-0.57	30	31
SOS1	0	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.048	0.17	-10000	0	-0.82	36	36
DAPP1	-0.05	0.19	-10000	0	-0.96	35	35
cytokine secretion	-0.016	0.12	-10000	0	-0.52	34	34
mol:DAG	-0.029	0.097	0.24	1	-0.5	30	31
PLCG2	-0.002	0.035	-10000	0	-0.79	2	2
MAP2K1	0.008	0.09	-10000	0	-0.48	17	17
B-cell antigen/BCR complex/FcgammaRIIB	-0.07	0.19	-10000	0	-0.55	122	122
mol:PI-3-4-5-P3	-0.044	0.093	0.34	2	-0.37	39	41
ETS1	0.004	0.088	-10000	0	-0.48	20	20
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.057	0.16	-10000	0	-0.51	97	97
B-cell antigen/BCR complex/LYN	-0.057	0.18	-10000	0	-0.57	97	97
MALT1	0	0	-10000	0	-10000	0	0
TRAF6	0.001	0.003	-10000	0	-10000	0	0
RAC1	-0.03	0.16	-10000	0	-0.71	33	33
B-cell antigen/BCR complex/LYN/SYK	-0.057	0.17	-10000	0	-0.55	98	98
CARD11	-0.014	0.1	0.24	1	-0.48	30	31
FCGR2B	-0.004	0.054	-10000	0	-0.71	6	6
PPP3CA	-0.001	0.013	-10000	0	-0.29	2	2
BCL10	0	0	-10000	0	-10000	0	0
IKK complex	0.017	0.027	0.091	2	-0.098	1	3
PTPRC	-0.009	0.073	-10000	0	-0.5	19	19
PDPK1	-0.029	0.062	0.22	2	-0.26	25	27
PPP3CB	0	0	-10000	0	-10000	0	0
PPP3CC	0	0	-10000	0	-10000	0	0
POU2F2	0.019	0.014	-10000	0	-0.14	1	1

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.002	0.01	-10000	0	-10000	0	0
HSPA8	0	0.003	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.1	0.2	0.24	2	-0.56	167	169
AKT1	0.014	0.006	-10000	0	-10000	0	0
GSC	-0.035	0.29	-10000	0	-1.5	41	41
NKX2-5	-0.045	0.1	-10000	0	-0.29	171	171
muscle cell differentiation	0.007	0.049	0.76	1	-10000	0	1
SMAD2-3/SMAD4/SP1	0.006	0.04	-10000	0	-0.45	2	2
SMAD4	0.014	0.041	-10000	0	-0.83	1	1
CBFB	0	0	-10000	0	-10000	0	0
SAP18	0	0.002	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.2	0.25	-10000	0	-0.52	411	411
SMAD3/SMAD4/VDR	0.005	0.03	-10000	0	-0.43	2	2
MYC	-0.017	0.12	-10000	0	-0.79	24	24
CDKN2B	0.03	0.13	-10000	0	-1.5	7	7
AP1	-0.12	0.2	-10000	0	-0.51	59	59
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.002	0.02	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0	0.041	-10000	0	-0.33	2	2
SP3	0	0	-10000	0	-10000	0	0
CREB1	0	0	-10000	0	-10000	0	0
FOXH1	-0.044	0.12	-10000	0	-0.29	203	203
SMAD3/SMAD4/GR	-0.009	0.071	-10000	0	-0.56	16	16
GATA3	-0.037	0.15	-10000	0	-0.57	69	69
SKI/SIN3/HDAC complex/NCoR1	0.002	0.014	-10000	0	-10000	0	0
MEF2C/TIF2	-0.054	0.12	-10000	0	-0.58	40	40
endothelial cell migration	-0.007	0.06	1.5	1	-10000	0	1
MAX	0.001	0.005	-10000	0	-10000	0	0
RBBP7	-0.002	0.025	-10000	0	-0.29	8	8
RBBP4	0	0.024	-10000	0	-0.79	1	1
RUNX2	-0.005	0.036	-10000	0	-0.29	17	17
RUNX3	-0.006	0.066	-10000	0	-0.58	12	12
RUNX1	-0.001	0.024	-10000	0	-0.79	1	1
CTBP1	0	0	-10000	0	-10000	0	0
NR3C1	-0.01	0.093	-10000	0	-0.79	15	15
VDR	0	0	-10000	0	-10000	0	0
CDKN1A	0.051	0.078	-10000	0	-1.5	2	2
KAT2B	0	0.024	-10000	0	-0.79	1	1
SMAD2/SMAD2/SMAD4/FOXH1	-0.029	0.071	-10000	0	-0.47	5	5
DCP1A	0	0	-10000	0	-10000	0	0
SKI	0	0.002	-10000	0	-10000	0	0
SERPINE1	0.007	0.061	-10000	0	-1.5	1	1
SMAD3/SMAD4/ATF2	-0.002	0.036	-10000	0	-0.55	3	3
SMAD3/SMAD4/ATF3	-0.081	0.2	-10000	0	-0.56	159	159
SAP30	-0.001	0.018	-10000	0	-0.29	4	4
Cbp/p300/PIAS3	0.005	0.023	-10000	0	-10000	0	0
JUN	-0.073	0.22	-10000	0	-0.51	53	53
SMAD3/SMAD4/IRF7	-0.02	0.068	-10000	0	-0.36	12	12
TFE3	0.017	0.006	-10000	0	-10000	0	0
COL1A2	0.028	0.1	-10000	0	-1.2	3	3
mesenchymal cell differentiation	0.004	0.034	0.54	1	-10000	0	1
DLX1	-0.054	0.13	-10000	0	-0.32	185	185
TCF3	0	0.009	-10000	0	-0.29	1	1
FOS	-0.22	0.37	-10000	0	-0.78	325	325
SMAD3/SMAD4/Max	-0.002	0.029	-10000	0	-0.54	1	1
Cbp/p300/SNIP1	0	0.002	-10000	0	-10000	0	0
ZBTB17	0	0.006	-10000	0	-10000	0	0
LAMC1	0.042	0.047	-10000	0	-0.62	2	2
TGIF2/HDAC complex/SMAD3/SMAD4	-0.001	0.028	-10000	0	-0.54	1	1
IRF7	-0.031	0.092	-10000	0	-0.31	104	104
ESR1	-0.15	0.29	-10000	0	-0.58	290	290
HNF4A	-0.006	0.041	-10000	0	-0.29	22	22
MEF2C	0.001	0.093	-10000	0	-0.66	3	3
SMAD2-3/SMAD4	-0.003	0.032	-10000	0	-0.53	1	1
Cbp/p300/Src-1	0.003	0.022	-10000	0	-0.52	1	1
IGHV3OR16-13	-0.001	0.01	-10000	0	-10000	0	0
TGIF2/HDAC complex	0	0	-10000	0	-10000	0	0
CREBBP	0.002	0.007	-10000	0	-10000	0	0
SKIL	-0.003	0.029	-10000	0	-0.29	11	11
HDAC1	0	0.002	-10000	0	-10000	0	0
HDAC2	0	0.002	-10000	0	-10000	0	0
SNIP1	0.001	0.003	-10000	0	-10000	0	0
GCN5L2	0.001	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.001	0.029	-10000	0	-0.53	1	1
MSG1/HSC70	-0.23	0.29	-10000	0	-0.6	411	411
SMAD2	0.015	0.02	-10000	0	-10000	0	0
SMAD3	0.015	0.029	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.034	0.038	-10000	0	-0.33	3	3
SMAD2/SMAD2/SMAD4	0.027	0.039	-10000	0	-1.1	1	1
NCOR1	0	0.024	-10000	0	-0.79	1	1
NCOA2	-0.038	0.17	-10000	0	-0.79	53	53
NCOA1	-0.001	0.024	-10000	0	-0.79	1	1
MYOD/E2A	-0.003	0.022	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.029	0.051	-10000	0	-0.42	2	2
IFNB1	0.011	0.094	-10000	0	-0.42	19	19
SMAD3/SMAD4/MEF2C	-0.026	0.074	-10000	0	-0.76	2	2
CITED1	-0.3	0.38	-10000	0	-0.77	426	426
SMAD2-3/SMAD4/ARC105	0	0.028	-10000	0	-0.47	1	1
RBL1	-0.003	0.043	-10000	0	-0.59	5	5
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.048	0.062	-10000	0	-0.49	7	7
RUNX1-3/PEBPB2	-0.004	0.049	-10000	0	-0.58	7	7
SMAD7	-0.066	0.14	-10000	0	-0.58	8	8
MYC/MIZ-1	-0.012	0.09	-10000	0	-0.61	24	24
SMAD3/SMAD4	0.017	0.06	0.28	38	-0.43	2	40
IL10	0.019	0.12	-10000	0	-0.5	42	42
PIASy/HDAC complex	0.01	0.005	-10000	0	-10000	0	0
PIAS3	0.001	0.005	-10000	0	-10000	0	0
CDK2	0.002	0.008	-10000	0	-10000	0	0
IL5	0.014	0.11	-10000	0	-0.5	38	38
CDK4	0.001	0.02	-10000	0	-0.29	4	4
PIAS4	0.01	0.005	-10000	0	-10000	0	0
ATF3	-0.12	0.28	-10000	0	-0.79	158	158
SMAD3/SMAD4/SP1	0	0.032	-10000	0	-0.52	2	2
FOXG1	-0.023	0.077	-10000	0	-0.29	81	81
FOXO3	0.025	0.034	-10000	0	-0.6	3	3
FOXO1	0.02	0.063	-10000	0	-0.6	11	11
FOXO4	0.026	0.008	-10000	0	-10000	0	0
heart looping	0.001	0.093	-10000	0	-0.65	3	3
CEBPB	0.012	0.003	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.03	0.08	-10000	0	-0.55	11	11
MYOD1	-0.004	0.033	-10000	0	-10000	0	0
SMAD3/SMAD4/HNF4	-0.006	0.037	-10000	0	-0.68	1	1
SMAD3/SMAD4/GATA3	-0.024	0.11	-10000	0	-0.56	40	40
SnoN/SIN3/HDAC complex/NCoR1	-0.003	0.029	-10000	0	-0.29	11	11
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.001	0.051	-10000	0	-0.52	8	8
SMAD3/SMAD4/SP1-3	0.003	0.029	-10000	0	-0.45	2	2
MED15	0	0	-10000	0	-10000	0	0
SP1	0.019	0.014	-10000	0	-10000	0	0
SIN3B	0	0.002	-10000	0	-10000	0	0
SIN3A	0	0.002	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.014	0.09	-10000	0	-0.47	6	6
ITGB5	0.052	0.046	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.002	0.012	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.075	0.19	-10000	0	-0.55	147	147
AR	-0.11	0.27	-10000	0	-0.79	147	147
negative regulation of cell growth	-0.026	0.073	-10000	0	-0.48	2	2
SMAD3/SMAD4/MYOD	-0.006	0.034	-10000	0	-0.54	1	1
E2F5	-0.005	0.039	-10000	0	-0.29	20	20
E2F4	0	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.003	0.056	-10000	0	-0.44	2	2
SMAD2-3/SMAD4/FOXO1-3a-4	0.003	0.046	-10000	0	-0.34	6	6
TFDP1	-0.001	0.018	-10000	0	-0.29	4	4
SMAD3/SMAD4/AP1	-0.12	0.2	-10000	0	-0.55	44	44
SMAD3/SMAD4/RUNX2	-0.004	0.034	-10000	0	-0.54	1	1
TGIF2	0	0	-10000	0	-10000	0	0
TGIF1	0	0	-10000	0	-10000	0	0
ATF2	-0.001	0.034	-10000	0	-0.79	2	2

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.005	0.037	-10000	0	-10000	0	0
GNB1/GNG2	-0.015	0.048	-10000	0	-0.2	41	41
AKT1	0.05	0.072	-10000	0	-0.21	30	30
EGF	-0.16	0.31	-10000	0	-0.78	216	216
mol:TXA2	0	0	-10000	0	-10000	0	0
FGR	-0.01	0.052	-10000	0	-0.54	3	3
mol:Ca2+	0.047	0.1	-10000	0	-0.3	64	64
LYN	-0.01	0.05	-10000	0	-0.51	2	2
RhoA/GTP	-0.008	0.03	-10000	0	-0.14	2	2
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	0.052	0.11	-10000	0	-0.35	64	64
GNG2	-0.009	0.086	-10000	0	-0.79	13	13
ARRB2	0	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.029	0.058	-10000	0	-0.53	8	8
G beta5/gamma2	-0.019	0.064	-10000	0	-0.28	40	40
PRKCH	0.048	0.11	-10000	0	-0.35	64	64
DNM1	-0.005	0.064	-10000	0	-0.73	8	8
TXA2/TP beta/beta Arrestin3	-0.004	0.027	-10000	0	-0.3	7	7
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
PTGDR	-0.03	0.15	-10000	0	-0.71	46	46
G12 family/GTP	-0.022	0.073	-10000	0	-0.31	64	64
ADRBK1	0	0	-10000	0	-10000	0	0
ADRBK2	-0.004	0.053	-10000	0	-0.79	5	5
RhoA/GTP/ROCK1	0	0.016	-10000	0	-0.53	1	1
mol:GDP	-0.036	0.081	0.36	23	-10000	0	23
mol:NADP	0	0	-10000	0	-10000	0	0
RAB11A	-0.001	0.013	-10000	0	-0.29	2	2
PRKG1	-0.053	0.2	-10000	0	-0.79	73	73
mol:IP3	0.047	0.12	-10000	0	-0.38	64	64
cell morphogenesis	0	0.016	-10000	0	-0.52	1	1
PLCB2	0.045	0.15	-10000	0	-0.52	64	64
mol:cGMP	0	0	-10000	0	-10000	0	0
BLK	-0.008	0.062	-10000	0	-0.44	6	6
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.011	0.05	-10000	0	-0.51	2	2
RHOA	0	0	-10000	0	-10000	0	0
PTGIR	-0.002	0.027	-10000	0	-0.29	9	9
PRKCB1	0.045	0.12	-10000	0	-0.38	64	64
GNAQ	-0.002	0.041	-10000	0	-0.79	3	3
mol:L-citrulline	0	0	-10000	0	-10000	0	0
TXA2/TXA2-R family	0.047	0.16	-10000	0	-0.55	64	64
LCK	-0.015	0.071	-10000	0	-0.47	15	15
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.012	0.056	-10000	0	-0.35	1	1
TXA2-R family/G12 family/GDP/G beta/gamma	0.025	0.035	-10000	0	-0.29	8	8
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.011	0.054	-10000	0	-0.34	1	1
MAPK14	0.051	0.079	-10000	0	-0.24	38	38
TGM2/GTP	0.047	0.13	-10000	0	-0.43	64	64
MAPK11	0.051	0.082	-10000	0	-0.24	64	64
ARHGEF1	0.038	0.061	-10000	0	-0.18	38	38
GNAI2	0	0	-10000	0	-10000	0	0
JNK cascade	0.049	0.12	-10000	0	-0.4	64	64
RAB11/GDP	-0.001	0.012	-10000	0	-0.29	2	2
ICAM1	0.046	0.093	-10000	0	-0.28	64	64
cAMP biosynthetic process	0.043	0.12	-10000	0	-0.36	64	64
Gq family/GTP/EBP50	0.017	0.038	-10000	0	-0.31	4	4
actin cytoskeleton reorganization	0	0.016	-10000	0	-0.52	1	1
SRC	-0.01	0.05	-10000	0	-0.51	2	2
GNB5	0	0	-10000	0	-10000	0	0
GNB1	0	0	-10000	0	-10000	0	0
EGF/EGFR	-0.029	0.1	-10000	0	-0.33	30	30
VCAM1	0.044	0.1	-10000	0	-0.32	64	64
TP beta/Gq family/GDP/G beta5/gamma2	0.029	0.058	-10000	0	-0.53	8	8
platelet activation	0.066	0.1	-10000	0	-0.31	64	64
PGI2/IP	-0.002	0.018	-10000	0	-10000	0	0
PRKACA	-0.014	0.069	-10000	0	-0.37	39	39
Gq family/GDP/G beta5/gamma2	0.027	0.06	-10000	0	-0.52	8	8
TXA2/TP beta/beta Arrestin2	-0.005	0.053	-10000	0	-0.65	7	7
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.01	0.07	-10000	0	-0.34	39	39
mol:DAG	0.046	0.13	-10000	0	-0.42	64	64
EGFR	-0.3	0.38	-10000	0	-0.78	414	414
TXA2/TP alpha	0.048	0.15	-10000	0	-0.5	64	64
Gq family/GTP	-0.004	0.035	-10000	0	-0.27	17	17
YES1	-0.01	0.051	-10000	0	-0.46	3	3
GNAI2/GTP	-0.012	0.058	-10000	0	-0.46	5	5
PGD2/DP	-0.023	0.11	-10000	0	-0.59	41	41
SLC9A3R1	-0.026	0.083	-10000	0	-10000	0	0
FYN	-0.011	0.053	-10000	0	-0.5	4	4
mol:NO	0	0	-10000	0	-10000	0	0
GNA15	-0.003	0.033	-10000	0	-0.36	8	8
PGK/cGMP	-0.035	0.13	-10000	0	-0.53	73	73
RhoA/GDP	0	0	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.017	0.079	-10000	0	-0.59	12	12
NOS3	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
PRKCA	0.042	0.12	-10000	0	-0.38	71	71
PRKCB	0.043	0.12	-10000	0	-0.37	73	73
PRKCE	0.05	0.11	-10000	0	-0.35	64	64
PRKCD	0.048	0.12	-10000	0	-0.38	64	64
PRKCG	0.044	0.12	-10000	0	-0.39	64	64
muscle contraction	0.05	0.15	-10000	0	-0.5	64	64
PRKCZ	0.052	0.11	-10000	0	-0.35	64	64
ARR3	-0.002	0.025	-10000	0	-0.29	8	8
TXA2/TP beta	-0.013	0.065	-10000	0	-0.5	6	6
PRKCQ	0.037	0.14	-10000	0	-0.39	79	79
MAPKKK cascade	0.044	0.14	-10000	0	-0.48	64	64
SELE	0.038	0.12	-10000	0	-0.42	64	64
TP beta/GNAI2/GDP/G beta/gamma	-0.015	0.079	-10000	0	-0.57	13	13
ROCK1	-0.001	0.024	-10000	0	-0.79	1	1
GNA14	-0.013	0.085	-10000	0	-0.45	32	32
chemotaxis	0.046	0.18	-10000	0	-0.62	64	64
GNA12	0	0	-10000	0	-10000	0	0
GNA13	0	0	-10000	0	-10000	0	0
GNA11	-0.002	0.041	-10000	0	-0.79	3	3
Rac1/GTP	0	0	-10000	0	-10000	0	0

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	-0.026	0.032	-9999	-10000	0	0
BIRC5	-0.21	0.13	-9999	-0.29	779	779
NFKBIA	-0.024	0.034	-9999	-10000	0	0
CPEB1	-0.15	0.31	-9999	-0.79	204	204
AKT1	-0.024	0.034	-9999	-10000	0	0
NDEL1	0	0	-9999	-10000	0	0
Aurora A/BRCA1	-0.024	0.033	-9999	-0.55	1	1
NDEL1/TACC3	-0.041	0.061	-9999	-10000	0	0
GADD45A	0	0	-9999	-10000	0	0
GSK3B	0.003	0.004	-9999	-10000	0	0
PAK1/Aurora A	-0.03	0.04	-9999	-10000	0	0
MDM2	-0.001	0.02	-9999	-0.29	5	5
JUB	-0.003	0.048	-9999	-0.79	4	4
TPX2	-0.11	0.1	-9999	-10000	0	0
TP53	-0.011	0.017	-9999	-10000	0	0
DLG7	-0.03	0.037	-9999	-10000	0	0
AURKAIP1	-0.003	0.031	-9999	-0.29	12	12
ARHGEF7	0	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	-0.044	0.066	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.024	0.033	-9999	-0.54	1	1
AURKA	-0.037	0.046	-9999	-10000	0	0
AURKB	-0.01	0.011	-9999	-10000	0	0
CDC25B	-0.018	0.026	-9999	-10000	0	0
G2/M transition checkpoint	-0.025	0.04	-9999	-0.49	4	4
mRNA polyadenylation	-0.11	0.2	-9999	-0.52	204	204
Aurora A/CPEB	-0.12	0.2	-9999	-0.52	204	204
Aurora A/TACC1/TRAP/chTOG	-0.032	0.088	-9999	-0.47	41	41
BRCA1	-0.001	0.027	-9999	-0.46	3	3
centrosome duplication	-0.03	0.04	-9999	-10000	0	0
regulation of centrosome cycle	-0.04	0.061	-9999	-10000	0	0
spindle assembly	-0.032	0.087	-9999	-0.46	41	41
TDRD7	0	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.1	0.072	-9999	-0.61	1	1
CENPA	-0.006	0.012	-9999	-10000	0	0
Aurora A/PP2A	-0.026	0.032	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.006	0.029	-9999	-10000	0	0
negative regulation of DNA binding	-0.009	0.02	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	-0.001	0.013	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
Ajuba/Aurora A	-0.025	0.04	-9999	-0.5	4	4
mitotic prometaphase	-0.012	0.011	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.037	0.046	-9999	-10000	0	0
TACC1	-0.03	0.15	-9999	-0.79	41	41
TACC3	-0.046	0.11	-9999	-0.29	173	173
Aurora A/Antizyme1	-0.022	0.025	-9999	-10000	0	0
Aurora A/RasGAP	-0.026	0.032	-9999	-10000	0	0
OAZ1	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.003	0.004	-9999	-10000	0	0
GIT1	-0.001	0.02	-9999	-0.29	5	5
GIT1/beta-PIX/PAK1	-0.004	0.023	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.11	0.1	-9999	-10000	0	0
PPP2R5D	0	0	-9999	-10000	0	0
Aurora A/TPX2	-0.11	0.09	-9999	-10000	0	0
PAK1	-0.007	0.044	-9999	-0.29	25	25
CKAP5	0	0	-9999	-10000	0	0

×

Arf6 trafficking events

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
SLC2A4	-0.44	0.39	-10000	0	-0.79	610	610
CLTC	0.027	0.018	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.024	0.02	-10000	0	-10000	0	0
Dynamin 2/GTP	-0.006	0.028	-10000	0	-10000	0	0
EXOC4	0	0	-10000	0	-10000	0	0
CD59	0.025	0.019	-10000	0	-10000	0	0
CPE	0.006	0.08	-10000	0	-0.53	24	24
CTNNB1	0	0	-10000	0	-10000	0	0
membrane fusion	-0.002	0.019	-10000	0	-10000	0	0
CTNND1	0.025	0.031	-10000	0	-10000	0	0
DNM2	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.03	0.014	-10000	0	-10000	0	0
TSHR	-0.007	0.11	-10000	0	-0.53	49	49
INS	0.011	0.005	-10000	0	-10000	0	0
BIN1	-0.007	0.072	-10000	0	-0.74	10	10
mol:Choline	-0.002	0.019	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.01	0.037	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.006	0.028	-10000	0	-10000	0	0
JUP	0.025	0.017	-10000	0	-10000	0	0
ASAP2/amphiphysin II	-0.004	0.046	-10000	0	-0.48	10	10
ARF6/GTP	0	0	-10000	0	-10000	0	0
CDH1	0.017	0.05	-10000	0	-0.37	1	1
clathrin-independent pinocytosis	0	0	-10000	0	-10000	0	0
MAPK8IP3	0	0.009	-10000	0	-10000	0	0
positive regulation of endocytosis	0	0	-10000	0	-10000	0	0
EXOC2	-0.005	0.037	-10000	0	-0.29	18	18
substrate adhesion-dependent cell spreading	0	0.001	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.009	0.033	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.018	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0	0.005	-10000	0	-10000	0	0
ACAP1	-0.001	0.019	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.02	0.015	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.032	0.022	-10000	0	-10000	0	0
JIP4/KLC1	0	0	-10000	0	-10000	0	0
EXOC1	0	0	-10000	0	-10000	0	0
exocyst	0	0.001	-10000	0	-10000	0	0
RALA/GTP	0	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0	0	-10000	0	-10000	0	0
receptor recycling	0	0	-10000	0	-10000	0	0
CTNNA1	0.025	0.031	-10000	0	-10000	0	0
NME1	0.01	0.038	-10000	0	-10000	0	0
clathrin coat assembly	0.027	0.018	-10000	0	-10000	0	0
IL2RA	0.017	0.045	-10000	0	-0.37	7	7
VAMP3	0.018	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.22	0.2	-10000	0	-0.39	610	610
EXOC6	0	0	-10000	0	-10000	0	0
PLD1	-0.003	0.032	-10000	0	-0.34	10	10
PLD2	0	0	-10000	0	-10000	0	0
EXOC5	0	0	-10000	0	-10000	0	0
PIP5K1C	0.03	0.014	-10000	0	-10000	0	0
SDC1	0.021	0.024	-10000	0	-0.35	1	1
ARF6/GDP	-0.008	0.033	-10000	0	-10000	0	0
EXOC7	0	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.009	0.033	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.002	0.019	-10000	0	-10000	0	0
endocytosis	0.004	0.045	0.47	10	-10000	0	10
SCAMP2	0	0	-10000	0	-10000	0	0
ADRB2	-0.07	0.19	-10000	0	-0.42	250	250
EXOC3	0	0	-10000	0	-10000	0	0
ASAP2	-0.001	0.024	-10000	0	-0.79	1	1
Dynamin 2/GDP	-0.006	0.028	-10000	0	-10000	0	0
KLC1	0	0	-10000	0	-10000	0	0
AVPR2	-0.13	0.22	-10000	0	-0.42	397	397
RALA	0	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.007	0.028	-10000	0	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.001	0.004	-9999	-10000	0	0
HDAC2	0.001	0.004	-9999	-10000	0	0
GNB1/GNG2	-0.01	0.074	-9999	-0.54	20	20
forebrain development	-0.024	0.2	-9999	-0.51	135	135
GNAO1	-0.021	0.13	-9999	-0.49	67	67
SMO/beta Arrestin2	-0.005	0.052	-9999	-0.6	8	8
SMO	0.005	0.069	-9999	-0.74	9	9
ARRB2	0.011	0.004	-9999	-10000	0	0
GLI3/SPOP	0.044	0.037	-9999	-10000	0	0
mol:GTP	0	0.003	-9999	-10000	0	0
GSK3B	0	0	-9999	-10000	0	0
GNAI2	0.01	0.004	-9999	-10000	0	0
SIN3/HDAC complex	0	0.007	-9999	-10000	0	0
GNAI1	-0.036	0.18	-9999	-0.79	62	62
XPO1	0.012	0.004	-9999	-10000	0	0
GLI1/Su(fu)	-0.054	0.16	-9999	-0.53	71	71
SAP30	0	0.018	-9999	-0.29	4	4
mol:GDP	0.005	0.069	-9999	-0.74	9	9
MIM/GLI2A	0.002	0.028	-9999	-0.3	9	9
IFT88	0	0	-9999	-10000	0	0
GNAI3	0.01	0.004	-9999	-10000	0	0
GLI2	0.04	0.036	-9999	-10000	0	0
GLI3	0.04	0.039	-9999	-10000	0	0
CSNK1D	0	0	-9999	-10000	0	0
CSNK1E	0	0	-9999	-10000	0	0
SAP18	0.001	0.004	-9999	-10000	0	0
embryonic digit morphogenesis	0	0	-9999	-10000	0	0
GNG2	-0.009	0.086	-9999	-0.79	13	13
Gi family/GTP	-0.001	0.1	-9999	-0.36	49	49
SIN3B	0.001	0.004	-9999	-10000	0	0
SIN3A	0.001	0.004	-9999	-10000	0	0
GLI3/Su(fu)	-0.002	0.025	-9999	-0.44	1	1
GLI2/Su(fu)	0.008	0.046	-9999	-0.39	6	6
FOXA2	-0.012	0.032	-9999	-10000	0	0
neural tube patterning	-0.024	0.2	-9999	-0.51	135	135
SPOP	0	0	-9999	-10000	0	0
Su(fu)/PIAS1	-0.002	0.025	-9999	-0.45	1	1
GNB1	0	0	-9999	-10000	0	0
CSNK1G2	0	0	-9999	-10000	0	0
CSNK1G3	0	0	-9999	-10000	0	0
MTSS1	0.002	0.029	-9999	-0.3	9	9
embryonic limb morphogenesis	-0.024	0.2	-9999	-0.51	135	135
SUFU	0.004	0.031	-9999	-0.34	4	4
LGALS3	-0.012	0.095	-9999	-0.79	16	16
catabolic process	-0.004	0.027	-9999	-10000	0	0
GLI3A/CBP	-0.008	0.098	-9999	-0.38	70	70
KIF3A	0	0	-9999	-10000	0	0
GLI1	-0.026	0.21	-9999	-0.52	135	135
RAB23	0	0	-9999	-10000	0	0
CSNK1A1	0	0	-9999	-10000	0	0
IFT172	-0.001	0.024	-9999	-0.79	1	1
RBBP7	-0.001	0.025	-9999	-0.29	8	8
Su(fu)/Galectin3	-0.009	0.067	-9999	-0.52	17	17
GNAZ	0.003	0.072	-9999	-0.79	9	9
RBBP4	0.001	0.024	-9999	-0.79	1	1
CSNK1G1	0	0	-9999	-10000	0	0
PIAS1	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GLI2/SPOP	-0.004	0.026	-9999	-10000	0	0
STK36	0.011	0.025	-9999	-0.79	1	1
Gi family/GNB1/GNG2/GDP	-0.03	0.1	-9999	-0.47	27	27
PTCH1	-0.066	0.34	-9999	-1.1	91	91
MIM/GLI1	-0.018	0.19	-9999	-0.57	74	74
CREBBP	-0.008	0.097	-9999	-0.38	70	70
Su(fu)/SIN3/HDAC complex	0.007	0.022	-9999	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.022	0	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0	0.007	-10000	0	-10000	0	0
CDKN1B	0.036	0.024	-10000	0	-0.42	3	3
CDKN1A	0.036	0.02	-10000	0	-0.42	2	2
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	-0.001	0.018	-10000	0	-0.29	4	4
FOXO3	0.036	0.024	-10000	0	-0.42	3	3
AKT1	0	0.001	-10000	0	-10000	0	0
BAD	0	0.009	-10000	0	-0.29	1	1
AKT3	0.009	0.059	-10000	0	-0.44	19	19
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.037	0.003	-10000	0	-10000	0	0
AKT1/ASK1	-0.001	0.025	-10000	0	-0.41	4	4
BAD/YWHAZ	-0.001	0.009	-10000	0	-10000	0	0
RICTOR	0	0	-10000	0	-10000	0	0
RAF1	0	0	-10000	0	-10000	0	0
JNK cascade	0.001	0.024	0.4	4	-10000	0	4
TSC1	0.037	0.003	-10000	0	-10000	0	0
YWHAZ	-0.001	0.015	-10000	0	-0.29	3	3
AKT1/RAF1	0	0.001	-10000	0	-10000	0	0
EP300	0	0	-10000	0	-10000	0	0
mol:GDP	0	0.001	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.037	0.003	-10000	0	-10000	0	0
YWHAQ	0	0	-10000	0	-10000	0	0
TBC1D4	0.022	0.04	-10000	0	-0.51	6	6
MAP3K5	-0.003	0.048	-10000	0	-0.79	4	4
MAPKAP1	0	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.04	0.022	-10000	0	-10000	0	0
YWHAH	0	0	-10000	0	-10000	0	0
AKT1S1	0.037	0.003	-10000	0	-10000	0	0
CASP9	0.037	0.003	-10000	0	-10000	0	0
YWHAB	0	0	-10000	0	-10000	0	0
p27Kip1/KPNA1	-0.001	0.021	-10000	0	-0.39	3	3
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0	0.006	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0
SRC	0	0.009	-10000	0	-0.29	1	1
AKT2/p21CIP1	-0.001	0.017	-10000	0	-0.4	2	2
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.018	0.001	-10000	0	-10000	0	0
CHUK	0.037	0.003	-10000	0	-10000	0	0
BAD/BCL-XL	0	0.003	-10000	0	-10000	0	0
mTORC2	0	0	-10000	0	-10000	0	0
AKT2	0.017	0	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.054	0.03	-10000	0	-10000	0	0
PDPK1	0	0	-10000	0	-10000	0	0
MDM2	0.037	0.01	-10000	0	-10000	0	0
MAPKKK cascade	0	0.001	-10000	0	-10000	0	0
MDM2/Cbp/p300	0	0.005	-10000	0	-10000	0	0
TSC1/TSC2	0.044	0.002	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0.005	-10000	0	-10000	0	0
glucose import	-0.25	0.25	-10000	0	-0.47	612	612
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.031	0.002	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.25	0.25	-10000	0	-0.47	612	612
GSK3A	0.037	0.003	-10000	0	-10000	0	0
FOXO1	0.033	0.046	-10000	0	-0.42	11	11
GSK3B	0.037	0.003	-10000	0	-10000	0	0
SFN	-0.016	0.099	-10000	0	-0.51	35	35
G1/S transition of mitotic cell cycle	0.044	0.003	-10000	0	-10000	0	0
p27Kip1/14-3-3 family	0.043	0.032	-10000	0	-10000	0	0
PRKACA	0	0	-10000	0	-10000	0	0
KPNA1	0	0	-10000	0	-10000	0	0
HSP90AA1	0	0.009	-10000	0	-0.29	1	1
YWHAG	0	0	-10000	0	-10000	0	0
RHEB	0	0	-10000	0	-10000	0	0
CREBBP	0	0	-10000	0	-10000	0	0

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.022	0.02	-10000	0	-0.6	1	1
MAP4K4	0.041	0.044	-10000	0	-0.68	1	1
BAG4	-0.006	0.055	-10000	0	-0.44	14	14
PKC zeta/ceramide	-0.023	0.047	0.18	1	-0.57	1	2
NFKBIA	0	0	-10000	0	-10000	0	0
BIRC3	-0.01	0.077	-10000	0	-0.51	21	21
BAX	-0.008	0.021	-10000	0	-10000	0	0
RIPK1	0	0	-10000	0	-10000	0	0
AKT1	0.024	0.009	-10000	0	-10000	0	0
BAD	-0.022	0.045	0.2	1	-0.25	1	2
SMPD1	0.026	0.032	-10000	0	-0.24	13	13
RB1	-0.022	0.049	0.2	1	-0.47	2	3
FADD/Caspase 8	0.049	0.046	-10000	0	-0.64	1	1
MAP2K4	-0.014	0.046	-10000	0	-0.45	2	2
NSMAF	0	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.014	0.045	-10000	0	-0.45	1	1
EGF	-0.16	0.31	-10000	0	-0.78	216	216
mol:ceramide	-0.033	0.047	0.21	1	-10000	0	1
MADD	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.021	0.023	-10000	0	-0.6	1	1
ASAH1	-0.001	0.015	-10000	0	-0.29	3	3
negative regulation of cell cycle	-0.022	0.048	0.2	1	-0.46	2	3
cell proliferation	-0.094	0.16	-10000	0	-0.38	246	246
BID	0.024	0.033	-10000	0	-0.39	1	1
MAP3K1	-0.022	0.047	0.2	1	-0.47	1	2
EIF2A	-0.005	0.041	-10000	0	-10000	0	0
TRADD	0	0	-10000	0	-10000	0	0
CRADD	0	0	-10000	0	-10000	0	0
MAPK3	-0.002	0.043	-10000	0	-0.41	1	1
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.002	0.043	-10000	0	-0.41	1	1
Cathepsin D/ceramide	-0.027	0.05	0.18	1	-0.25	2	3
FADD	0.039	0.048	-10000	0	-0.47	3	3
KSR1	-0.022	0.048	0.2	1	-0.33	3	4
MAPK8	-0.012	0.054	0.2	1	-0.35	10	11
PRKRA	-0.022	0.045	0.2	1	-10000	0	1
PDGFA	-0.001	0.025	-10000	0	-0.79	1	1
TRAF2	-0.001	0.018	-10000	0	-0.29	4	4
IGF1	-0.18	0.33	-10000	0	-0.79	246	246
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.033	0.047	0.21	1	-10000	0	1
CTSD	-0.01	0.053	-10000	0	-0.29	37	37
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	-0.1	0.17	-10000	0	-0.41	246	246
PRKCD	0	0.009	-10000	0	-0.29	1	1
PRKCZ	-0.001	0.024	-10000	0	-0.79	1	1
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.021	0.023	-10000	0	-0.6	1	1
RelA/NF kappa B1	0	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	-0.001	0.024	-10000	0	-0.79	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.006	0.04	-10000	0	-0.72	1	1
TNFR1A/BAG4/TNF-alpha	-0.013	0.069	-10000	0	-0.53	17	17
mol:Sphingosine-1-phosphate	0.022	0.02	-10000	0	-0.6	1	1
MAP2K1	-0.005	0.043	-10000	0	-0.42	1	1
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
CYCS	-0.007	0.043	0.18	25	-10000	0	25
TNFRSF1A	0	0	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
TNFR1A/BAG4	-0.004	0.04	-10000	0	-0.6	4	4
EIF2AK2	-0.013	0.042	0.2	1	-10000	0	1
TNF-alpha/TNFR1A/FAN	-0.009	0.06	-10000	0	-0.52	13	13
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	-0.002	0.02	-10000	0	-0.32	1	1
MAP2K2	-0.005	0.043	-10000	0	-0.42	1	1
SMPD3	0.025	0.041	-10000	0	-0.28	17	17
TNF	-0.016	0.096	-10000	0	-0.46	38	38
PKC zeta/PAR4	-0.001	0.026	-10000	0	-0.6	2	2
mol:PHOSPHOCHOLINE	0.045	0.11	0.27	215	-10000	0	215
NF kappa B1/RelA/I kappa B alpha	-0.001	0.019	-10000	0	-0.44	2	2
AIFM1	-0.007	0.043	0.18	25	-10000	0	25
BCL2	-0.027	0.14	-10000	0	-0.79	37	37

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	-0.007	0.072	-10000	0	-0.74	10	10
positive regulation of NF-kappaB transcription factor activity	-0.062	0.18	-10000	0	-0.6	113	113
MAP2K4	0.042	0.038	-10000	0	-0.42	1	1
IKBKB	-0.001	0.013	-10000	0	-0.29	2	2
TNFRSF10B	0	0	-10000	0	-10000	0	0
TNFRSF10A	-0.005	0.063	-10000	0	-0.79	7	7
SMPD1	-0.002	0.026	-10000	0	-0.28	9	9
IKBKG	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	-0.076	0.23	-10000	0	-0.78	105	105
TRAIL/TRAILR2	-0.005	0.055	-10000	0	-0.6	9	9
TRAIL/TRAILR3	-0.008	0.068	-10000	0	-0.65	11	11
TRAIL/TRAILR1	-0.009	0.073	-10000	0	-0.6	16	16
TRAIL/TRAILR4	-0.063	0.18	-10000	0	-0.6	113	113
TRAIL/TRAILR1/DAP3/GTP	-0.007	0.058	-10000	0	-0.48	16	16
IKK complex	-0.003	0.019	-10000	0	-10000	0	0
RIPK1	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0	0.006	-10000	0	-10000	0	0
MAPK3	0.017	0.057	-10000	0	-0.6	9	9
MAP3K1	-0.004	0.032	-10000	0	-0.32	10	10
TRAILR4 (trimer)	-0.075	0.23	-10000	0	-0.78	105	105
TRADD	0	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	-0.005	0.063	-10000	0	-0.79	7	7
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.005	0.039	-10000	0	-0.32	16	16
CFLAR	0	0	-10000	0	-10000	0	0
MAPK1	0.017	0.057	-10000	0	-0.6	9	9
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.008	0.055	-10000	0	-0.45	16	16
mol:ceramide	-0.002	0.025	-10000	0	-0.28	9	9
FADD	-0.004	0.035	-10000	0	-0.29	16	16
MAPK8	0.045	0.055	-10000	0	-0.44	9	9
TRAF2	-0.001	0.018	-10000	0	-0.29	4	4
TRAILR3 (trimer)	-0.004	0.048	-10000	0	-0.43	11	11
CHUK	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.01	0.065	-10000	0	-0.53	16	16
DAP3	0	0.009	-10000	0	-0.29	1	1
CASP10	0.021	0.11	0.31	98	-0.49	13	111
JNK cascade	-0.062	0.18	-10000	0	-0.6	113	113
TRAIL (trimer)	-0.007	0.072	-10000	0	-0.74	10	10
TNFRSF10C	-0.004	0.048	-10000	0	-0.43	11	11
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.008	0.056	-10000	0	-0.45	16	16
TRAIL/TRAILR2/FADD	-0.007	0.05	-10000	0	-0.52	9	9
cell death	-0.002	0.025	-10000	0	-0.28	9	9
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.003	0.029	-10000	0	-0.32	9	9
TRAILR2 (trimer)	0	0	-10000	0	-10000	0	0
CASP8	0.001	0.014	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.005	0.041	-10000	0	-0.44	9	9

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0	0	-10000	0	-10000	0	0
HDAC3	0	0	-10000	0	-10000	0	0
VDR	0	0	-10000	0	-10000	0	0
Cbp/p300/PCAF	0	0.016	-10000	0	-0.52	1	1
EP300	0	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.037	0.04	-10000	0	-0.32	5	5
KAT2B	-0.001	0.024	-10000	0	-0.79	1	1
MAPK14	0	0	-10000	0	-10000	0	0
AKT1	0.02	0.05	0.24	4	-0.34	13	17
RAR alpha/9cRA/Cyclin H	-0.011	0.064	-10000	0	-0.38	28	28
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.034	0.049	-10000	0	-0.32	15	15
CDC2	0.001	0.001	-10000	0	-10000	0	0
response to UV	0.001	0.001	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.012	0.068	-10000	0	-0.56	11	11
NCOR2	0	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0	0	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA	0.007	0.12	-10000	0	-0.56	34	34
NCOA2	-0.038	0.17	-10000	0	-0.79	53	53
NCOA3	0	0.009	-10000	0	-0.29	1	1
NCOA1	-0.001	0.024	-10000	0	-0.79	1	1
VDR/VDR/DNA	0	0	-10000	0	-10000	0	0
RARG	0.012	0.001	-10000	0	-10000	0	0
RAR gamma1/9cRA	0	0	-10000	0	-10000	0	0
MAPK3	0.011	0.002	-10000	0	-10000	0	0
MAPK1	0	0	-10000	0	-10000	0	0
MAPK8	0.006	0.068	-10000	0	-0.79	8	8
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.041	0.11	-10000	0	-0.62	28	28
RARA	0.014	0.062	-10000	0	-0.31	35	35
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.02	0.085	-10000	0	-0.29	65	65
PRKCA	-0.007	0.13	-10000	0	-0.76	30	30
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.004	0.13	-10000	0	-0.58	35	35
RXRG	-0.1	0.21	-10000	0	-0.44	287	287
RXRA	0.022	0.065	-10000	0	-0.32	35	35
RXRB	0.011	0.075	-10000	0	-0.43	28	28
VDR/Vit D3/DNA	0	0	-10000	0	-10000	0	0
RBP1	-0.026	0.097	-10000	0	-0.34	84	84
CRBP1/9-cic-RA	-0.018	0.07	-10000	0	-0.23	84	84
RARB	0.003	0.09	-10000	0	-0.79	14	14
PRKCG	-0.003	0.062	-10000	0	-0.29	49	49
MNAT1	0	0	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.007	0.12	-10000	0	-0.6	32	32
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.013	0.1	-10000	0	-0.49	33	33
proteasomal ubiquitin-dependent protein catabolic process	0.036	0.057	-10000	0	-0.44	6	6
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.004	0.13	-10000	0	-0.58	35	35
positive regulation of DNA binding	-0.011	0.06	-10000	0	-0.36	28	28
NRIP1	-0.002	0.12	-10000	0	-0.84	9	9
RXRs/RARs	-0.011	0.13	-10000	0	-0.57	35	35
RXRs/RXRs/DNA/9cRA	-0.045	0.11	-10000	0	-0.63	29	29
PRKACA	0	0	-10000	0	-10000	0	0
CDK7	0	0	-10000	0	-10000	0	0
TFIIH	0	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.006	0.035	-10000	0	-0.52	1	1
CCNH	0	0	-10000	0	-10000	0	0
CREBBP	0	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	0	0	-10000	0	-10000	0	0

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	0.005	0.094	0.23	1	-0.44	38	39
ACTA1	-0.018	0.13	0.27	1	-0.61	39	40
NUMA1	0.005	0.094	0.23	1	-0.44	38	39
SPTAN1	-0.005	0.12	0.27	1	-0.61	35	36
LIMK1	-0.005	0.13	-10000	0	-0.61	35	35
BIRC3	-0.01	0.077	-10000	0	-0.51	21	21
BIRC2	0	0	-10000	0	-10000	0	0
BAX	-0.001	0.02	-10000	0	-0.29	5	5
CASP10	-0.016	0.14	-10000	0	-0.65	39	39
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	0.005	0.094	0.23	1	-0.44	38	39
DIABLO	0	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.004	0.12	0.27	1	-0.6	35	36
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0	0	-10000	0	-10000	0	0
GSN	-0.01	0.14	0.27	1	-0.62	44	45
MADD	0	0	-10000	0	-10000	0	0
TFAP2A	0.014	0.083	-10000	0	-0.67	15	15
BID	0.005	0.063	-10000	0	-0.29	38	38
MAP3K1	0.004	0.042	-10000	0	-0.27	9	9
TRADD	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.005	0.12	0.27	1	-0.61	35	36
CASP9	0.002	0.004	-10000	0	-10000	0	0
DNA repair	-0.002	0.031	0.18	2	-0.22	4	6
neuron apoptosis	0.022	0.013	-10000	0	-10000	0	0
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.003	0.12	-10000	0	-0.58	35	35
APAF1	0.001	0.003	-10000	0	-10000	0	0
CASP6	0.023	0.057	-10000	0	-0.39	5	5
TRAF2	-0.001	0.018	-10000	0	-0.29	4	4
ICAD/CAD	0.003	0.12	-10000	0	-0.58	35	35
CASP7	-0.007	0.037	0.36	9	-10000	0	9
KRT18	0.015	0.024	-10000	0	-0.59	1	1
apoptosis	0.009	0.11	0.3	1	-0.52	35	36
DFFA	-0.005	0.12	0.27	1	-0.6	36	37
DFFB	-0.005	0.12	-10000	0	-0.61	35	35
PARP1	0.002	0.031	0.22	4	-0.19	2	6
actin filament polymerization	-0.002	0.12	0.55	39	-10000	0	39
TNF	-0.016	0.096	-10000	0	-0.46	38	38
CYCS	0.007	0.05	-10000	0	-0.21	36	36
SATB1	0.017	0.098	-10000	0	-0.47	31	31
SLK	-0.005	0.12	-10000	0	-0.61	35	35
p15 BID/BAX	-0.014	0.049	-10000	0	-0.35	8	8
CASP2	0.044	0.039	-10000	0	-0.45	1	1
JNK cascade	-0.004	0.042	0.27	9	-10000	0	9
CASP3	-0.014	0.13	0.28	1	-0.62	39	40
LMNB2	0.041	0.036	-10000	0	-0.38	2	2
RIPK1	0	0	-10000	0	-10000	0	0
CASP4	-0.001	0.024	-10000	0	-0.79	1	1
Mammalian IAPs/DIABLO	-0.005	0.044	-10000	0	-0.47	9	9
negative regulation of DNA binding	0.014	0.082	-10000	0	-0.66	15	15
stress fiber formation	-0.004	0.12	0.27	1	-0.6	35	36
GZMB	-0.029	0.15	-10000	0	-0.64	47	47
CASP1	0.014	0.034	-10000	0	-0.44	6	6
LMNB1	0.044	0.037	-10000	0	-0.38	2	2
APP	0.022	0.013	-10000	0	-10000	0	0
TNFRSF1A	0	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.011	0	-10000	0	-10000	0	0
VIM	0.003	0.1	0.3	1	-0.5	35	36
LMNA	0.04	0.036	-10000	0	-0.38	2	2
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.005	0.035	-10000	0	-0.48	1	1
LRDD	-0.001	0.02	-10000	0	-0.29	5	5
SREBF1	-0.008	0.13	-10000	0	-0.62	35	35
APAF-1/Caspase 9	-0.004	0.02	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0.005	0.093	0.23	1	-0.43	38	39
CFL2	0.001	0.12	-10000	0	-0.57	39	39
GAS2	-0.048	0.19	-10000	0	-0.52	129	129
positive regulation of apoptosis	0.045	0.036	-10000	0	-0.37	2	2
PRF1	-0.017	0.11	-10000	0	-0.64	29	29

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	-0.011	0.079	-10000	0	-0.6	19	19
ATM	0	0	-10000	0	-10000	0	0
UBE2D3	0	0	-10000	0	-10000	0	0
PRKDC	-0.001	0.018	-10000	0	-0.29	4	4
ATR	0	0	-10000	0	-10000	0	0
UBE2L3	0	0	-10000	0	-10000	0	0
FANCD2	0.024	0.01	-10000	0	-10000	0	0
protein ubiquitination	-0.029	0.074	-10000	0	-0.47	20	20
XRCC5	0	0	-10000	0	-10000	0	0
XRCC6	0	0	-10000	0	-10000	0	0
M/R/N Complex	0	0	-10000	0	-10000	0	0
MRE11A	0	0	-10000	0	-10000	0	0
DNA-PK	-0.001	0.009	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0	0.011	-10000	0	-10000	0	0
FANCF	0	0.009	-10000	0	-10000	0	0
BRCA1	-0.001	0.027	-10000	0	-0.46	3	3
CCNE1	-0.06	0.12	-10000	0	-0.29	223	223
CDK2/Cyclin E1	-0.038	0.075	-10000	0	-10000	0	0
FANCG	0	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	-0.012	0.081	-10000	0	-0.6	20	20
FANCE	0	0	-10000	0	-10000	0	0
FANCC	0	0	-10000	0	-10000	0	0
NBN	0	0	-10000	0	-10000	0	0
FANCA	-0.052	0.11	-10000	0	-10000	0	0
DNA repair	0.008	0.094	-10000	0	-0.47	6	6
BRCA1/BARD1/ubiquitin	-0.012	0.081	-10000	0	-0.6	20	20
BARD1/DNA-PK	-0.009	0.062	-10000	0	-0.47	19	19
FANCL	0	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.011	0.079	0.6	19	-10000	0	19
BRCA1/BARD1/CTIP/M/R/N Complex	-0.006	0.041	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1/TopBP1	-0.01	0.07	-10000	0	-0.52	20	20
BRCA1/BARD1/P53	-0.009	0.063	-10000	0	-0.47	20	20
BARD1/CSTF1/BRCA1	-0.01	0.07	-10000	0	-0.52	20	20
BRCA1/BACH1	-0.001	0.027	-10000	0	-0.46	3	3
BARD1	-0.014	0.1	-10000	0	-0.76	20	20
PCNA	-0.001	0.015	-10000	0	-0.29	3	3
BRCA1/BARD1/UbcH5C	-0.01	0.07	-10000	0	-0.52	20	20
BRCA1/BARD1/UbcH7	-0.01	0.07	-10000	0	-0.52	20	20
BRCA1/BARD1/RAD51/PCNA	-0.053	0.086	-10000	0	-0.51	20	20
BARD1/DNA-PK/P53	-0.008	0.058	-10000	0	-0.44	19	19
BRCA1/BARD1/Ubiquitin	-0.012	0.081	-10000	0	-0.6	20	20
BRCA1/BARD1/CTIP	-0.009	0.063	-10000	0	-0.47	20	20
FA complex	-0.005	0.011	-10000	0	-10000	0	0
BARD1/EWS	-0.011	0.079	-10000	0	-0.6	19	19
RBBP8	0.022	0.006	-10000	0	-10000	0	0
TP53	0	0	-10000	0	-10000	0	0
TOPBP1	0	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.009	0.063	0.47	20	-10000	0	20
BRCA1/BARD1	-0.029	0.075	-10000	0	-0.48	20	20
CSTF1	0	0.009	-10000	0	-0.29	1	1
BARD1/EWS-Fli1	-0.011	0.08	-10000	0	-0.61	19	19
CDK2	0	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.11	0.14	-10000	0	-0.29	396	396
RAD50	0	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.012	0.081	-10000	0	-0.6	20	20
EWSR1	0	0	-10000	0	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.018	0.084	-9999	-0.51	24	24
MAP4K1	-0.015	0.07	-9999	-0.31	53	53
MAP3K8	-0.007	0.072	-9999	-0.74	10	10
PRKCB	-0.02	0.11	-9999	-0.55	39	39
DBNL	0	0	-9999	-10000	0	0
CRKL	0	0	-9999	-10000	0	0
MAP3K1	0.036	0.054	-9999	-0.47	4	4
JUN	0.017	0.11	-9999	-0.6	34	34
MAP3K7	0.036	0.053	-9999	-0.32	19	19
GRAP2	-0.015	0.1	-9999	-0.72	22	22
CRK	0	0	-9999	-10000	0	0
MAP2K4	0.043	0.057	-9999	-0.32	20	20
LAT	-0.005	0.048	-9999	-0.35	17	17
LCP2	0	0.009	-9999	-0.29	1	1
MAPK8	0.013	0.12	-9999	-0.68	27	27
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.008	0.049	-9999	-0.35	19	19
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.016	0.078	-9999	-0.48	24	24

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	-0.002	0.042	-10000	0	-0.66	4	4
ANTXR2	-0.008	0.079	-10000	0	-0.79	11	11
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.001	0.011	-10000	0	-0.1	13	13
monocyte activation	0.004	0.073	-10000	0	-0.46	26	26
MAP2K2	-0.001	0.005	-10000	0	-10000	0	0
MAP2K1	-0.001	0.009	-10000	0	-10000	0	0
MAP2K7	-0.001	0.009	-10000	0	-10000	0	0
MAP2K6	-0.012	0.071	-10000	0	-0.47	25	25
CYAA	0.01	0.057	-10000	0	-0.49	13	13
MAP2K4	-0.001	0.017	-10000	0	-0.47	1	1
IL1B	0.007	0.065	-10000	0	-0.34	32	32
Channel	-0.006	0.058	-10000	0	-0.52	13	13
NLRP1	-0.008	0.06	-10000	0	-0.49	16	16
CALM1	0	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.001	0.013	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.001	0.011	0.1	13	-10000	0	13
MAPK3	-0.001	0.009	-10000	0	-10000	0	0
MAPK1	-0.001	0.009	-10000	0	-10000	0	0
PGR	-0.14	0.21	-10000	0	-0.47	314	314
PA/Cellular Receptors	-0.007	0.063	-10000	0	-0.56	13	13
apoptosis	-0.001	0.011	-10000	0	-0.1	13	13
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.006	0.054	-10000	0	-0.49	13	13
macrophage activation	0.02	0.01	-10000	0	-10000	0	0
TNF	-0.016	0.096	-10000	0	-0.46	38	38
VCAM1	-0.011	0.071	-10000	0	-0.46	26	26
platelet activation	-0.001	0.013	-10000	0	-10000	0	0
MAPKKK cascade	-0.013	0.022	0.1	26	-10000	0	26
IL18	0.011	0.036	-10000	0	-0.22	16	16
negative regulation of macrophage activation	-0.001	0.011	-10000	0	-0.1	13	13
LEF	-0.001	0.011	-10000	0	-0.1	13	13
CASP1	-0.005	0.031	-10000	0	-0.18	25	25
mol:cAMP	-0.001	0.013	-10000	0	-10000	0	0
necrosis	-0.001	0.011	-10000	0	-0.1	13	13
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.006	0.055	-10000	0	-0.5	13	13
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	0.03	0.007	-9999	-10000	0	0
SNTA1	0	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.017	0.046	-9999	-10000	0	0
MAPK12	0.017	0.083	-9999	-0.46	30	30
CCND1	0.015	0.043	-9999	-0.22	28	28
p38 gamma/SNTA1	-0.012	0.072	-9999	-0.43	30	30
MAP2K3	0	0.009	-9999	-0.29	1	1
PKN1	0	0.009	-9999	-0.29	1	1
G2/M transition checkpoint	0.017	0.082	-9999	-0.46	30	30
MAP2K6	0.01	0.085	-9999	-0.49	30	30
MAPT	-0.019	0.14	-9999	-0.4	119	119
MAPK13	0.022	0.009	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.014	0.031	-9999	-0.44	5	5

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.015	0.086	-9999	-0.52	31	31
E-cadherin/beta catenin	-0.017	0.098	-9999	-0.6	30	30
CTNNB1	0	0	-9999	-10000	0	0
JUP	-0.001	0.025	-9999	-0.54	2	2
CDH1	-0.022	0.13	-9999	-0.79	30	30

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.045	0.065	-10000	0	-0.51	5	5
UGCG	-0.011	0.095	-10000	0	-0.79	15	15
AKT1/mTOR/p70S6K/Hsp90/TERT	0.054	0.091	-10000	0	-0.39	12	12
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.013	0.097	-10000	0	-0.78	15	15
mol:DAG	0	0.002	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.026	0.09	-10000	0	-0.38	43	43
FRAP1	0.052	0.13	-10000	0	-0.41	64	64
FOXO3	0.06	0.11	-10000	0	-0.42	32	32
AKT1	0.055	0.11	-10000	0	-0.45	34	34
GAB2	0.007	0.044	-10000	0	-0.79	2	2
SMPD1	-0.002	0.014	-10000	0	-10000	0	0
SGMS1	-0.002	0.014	-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	0.015	0.06	-10000	0	-0.52	13	13
CALM1	0	0	-10000	0	-10000	0	0
cell proliferation	0.032	0.089	-10000	0	-0.35	39	39
EIF3A	0	0	-10000	0	-10000	0	0
PI3K	-0.007	0.065	-10000	0	-0.6	13	13
RPS6KB1	0.021	0.034	-10000	0	-10000	0	0
mol:sphingomyelin	0	0.002	-10000	0	-10000	0	0
natural killer cell activation	0	0.002	-10000	0	-0.012	22	22
JAK3	0.01	0.034	-10000	0	-0.29	14	14
PIK3R1	0.004	0.087	-10000	0	-0.79	13	13
JAK1	0.013	0.024	-10000	0	-0.79	1	1
NFKB1	0	0	-10000	0	-10000	0	0
MYC	0.046	0.18	-10000	0	-0.94	29	29
MYB	0.006	0.2	-10000	0	-1.3	23	23
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.052	0.094	-10000	0	-0.59	10	10
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.004	0.022	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.052	0.092	-10000	0	-0.57	10	10
Rac1/GDP	-0.006	0.052	-10000	0	-0.47	13	13
T cell proliferation	0.058	0.087	-10000	0	-0.52	10	10
SHC1	0.011	0.003	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.004	0.01	-10000	0	-0.066	23	23
PRKCZ	0.058	0.09	-10000	0	-0.55	10	10
NF kappa B1 p50/RelA	-0.025	0.088	-10000	0	-0.49	15	15
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.039	0.07	-10000	0	-0.53	6	6
HSP90AA1	0	0.009	-10000	0	-0.29	1	1
RELA	0	0	-10000	0	-10000	0	0
IL2RA	-0.02	0.12	-10000	0	-0.38	87	87
IL2RB	0.001	0.066	-10000	0	-0.31	42	42
TERT	-0.043	0.1	-10000	0	-0.29	160	160
E2F1	0.02	0.068	-10000	0	-0.44	23	23
SOS1	0.011	0.003	-10000	0	-10000	0	0
RPS6	0	0	-10000	0	-10000	0	0
mol:cAMP	-0.002	0.005	0.03	23	-10000	0	23
PTPN11	0.011	0.003	-10000	0	-10000	0	0
IL2RG	-0.004	0.088	-10000	0	-0.36	53	53
actin cytoskeleton organization	0.058	0.087	-10000	0	-0.52	10	10
GRB2	0.011	0.01	-10000	0	-0.29	1	1
IL2	0.006	0.026	-10000	0	-0.29	8	8
PIK3CA	0.013	0.01	-10000	0	-0.29	1	1
Rac1/GTP	0.026	0.053	-10000	0	-0.45	13	13
LCK	-0.007	0.1	-10000	0	-0.41	54	54
BCL2	0.039	0.2	-10000	0	-0.86	43	43

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0	0.009	-9999	-0.29	1	1
PLK4	-0.012	0.059	-9999	-0.29	46	46
regulation of centriole replication	0.013	0.042	-9999	-10000	0	0

×

IL1-mediated signaling events

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
UBC13/UEV1A	0	0.008	-10000	0	-10000	0	0
PRKCZ	-0.001	0.024	-10000	0	-0.79	1	1
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.007	0.042	-10000	0	-0.48	4	4
IRAK/TOLLIP	-0.001	0.01	-10000	0	-10000	0	0
IKBKB	-0.001	0.013	-10000	0	-0.29	2	2
IKBKG	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.031	0.12	-10000	0	-0.59	43	43
IL1A	-0.005	0.039	-10000	0	-0.29	20	20
IL1B	0.01	0.094	-10000	0	-0.68	18	18
IRAK/TRAF6/p62/Atypical PKCs	-0.001	0.014	-10000	0	-10000	0	0
IL1R2	-0.037	0.16	-10000	0	-0.57	71	71
IL1R1	-0.017	0.12	-10000	0	-0.79	24	24
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.001	0.064	0.24	34	-0.32	19	53
TOLLIP	0	0.009	-10000	0	-0.29	1	1
TICAM2	0	0	-10000	0	-10000	0	0
MAP3K3	0	0	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0	0.005	-10000	0	-10000	0	0
IKK complex/ELKS	0	0.004	-10000	0	-10000	0	0
JUN	0.031	0.079	-10000	0	-0.37	39	39
MAP3K7	0	0.009	-10000	0	-0.29	1	1
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.023	0.11	-10000	0	-0.48	51	51
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.013	0.074	-10000	0	-0.49	24	24
PIK3R1	-0.009	0.086	-10000	0	-0.79	13	13
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.012	0.069	-10000	0	-0.46	24	24
IL1 beta fragment/IL1R1/IL1RAP	-0.02	0.11	-10000	0	-0.54	40	40
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	0.027	0.074	-10000	0	-0.39	33	33
IRAK1	0.021	0.013	-10000	0	-10000	0	0
IL1RN/IL1R1	-0.021	0.097	-10000	0	-0.6	26	26
IRAK4	0	0	-10000	0	-10000	0	0
PRKCI	0	0.009	-10000	0	-10000	0	0
TRAF6	0	0	-10000	0	-10000	0	0
PI3K	-0.007	0.066	-10000	0	-0.6	13	13
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.012	0.063	-10000	0	-0.36	25	25
CHUK	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.02	0.11	-10000	0	-0.54	40	40
IL1 beta/IL1R2	-0.033	0.13	-10000	0	-0.56	57	57
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.001	0.008	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.02	0.097	-10000	0	-0.86	6	6
IRAK3	-0.032	0.16	-10000	0	-0.79	44	44
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.018	0.097	-10000	0	-0.48	40	40
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.008	0.05	-10000	0	-0.33	24	24
IL1 alpha/IL1R1/IL1RAP	-0.014	0.082	-10000	0	-0.54	24	24
RELA	0	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0	0.009	-10000	0	-0.29	1	1
MYD88	0	0	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	-0.001	0.008	-10000	0	-10000	0	0
IL1RAP	-0.001	0.024	-10000	0	-0.79	1	1
UBE2N	0	0	-10000	0	-10000	0	0
IRAK/TRAF6	-0.015	0.078	-10000	0	-0.81	4	4
CASP1	-0.004	0.053	-10000	0	-0.79	5	5
IL1RN/IL1R2	-0.035	0.12	-10000	0	-0.58	47	47
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.019	0.1	-10000	0	-0.5	40	40
TMEM189-UBE2V1	-0.001	0.013	-10000	0	-0.29	2	2
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.008	0.057	-10000	0	-0.38	24	24
PIK3CA	0	0.009	-10000	0	-0.29	1	1
IL1RN	-0.012	0.064	-10000	0	-0.32	41	41
TRAF6/TAK1/TAB1/TAB2	0	0.006	-10000	0	-10000	0	0
MAP2K6	-0.01	0.062	-10000	0	-0.41	25	25

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.024	0.077	0.5	6	-10000	0	6
GNAI2	0	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.005	0.035	-10000	0	-0.53	3	3
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.03	0.13	-10000	0	-0.49	67	67
RhoA/GTP	-0.024	0.078	-10000	0	-0.51	6	6
negative regulation of cAMP metabolic process	-0.028	0.087	-10000	0	-0.36	36	36
GNAZ	-0.007	0.071	-10000	0	-0.79	9	9
GNAI3	0	0	-10000	0	-10000	0	0
GNA12	0	0	-10000	0	-10000	0	0
S1PR5	-0.008	0.058	-10000	0	-0.35	25	25
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.028	0.088	-10000	0	-0.36	36	36
RhoA/GDP	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
GNAI1	-0.045	0.18	-10000	0	-0.79	62	62

×

S1P4 pathway

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
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.03	0.13	-9999	-0.49	67	67
CDC42/GTP	-0.026	0.077	-9999	-0.49	4	4
PLCG1	0.008	0.092	-9999	-0.5	4	4
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0	0	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
cell migration	-0.025	0.076	-9999	-0.48	4	4
S1PR5	-0.008	0.058	-9999	-0.35	25	25
S1PR4	-0.015	0.08	-9999	-0.36	46	46
MAPK3	0.008	0.092	-9999	-0.32	40	40
MAPK1	0.008	0.092	-9999	-0.37	12	12
S1P/S1P5/Gi	-0.028	0.088	-9999	-0.36	36	36
GNAI1	-0.045	0.18	-9999	-0.79	62	62
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.005	0.035	-9999	-0.53	3	3
RHOA	-0.006	0.038	-9999	-0.44	6	6
S1P/S1P4/Gi	-0.029	0.087	-9999	-0.34	40	40
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.007	0.071	-9999	-0.79	9	9
S1P/S1P4/G12/G13	-0.007	0.042	-9999	-0.48	6	6
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0

×

S1P3 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
PDGFRB	-0.003	0.048	-9999	-0.79	4	4
mol:S1P	0.001	0.004	-9999	-10000	0	0
S1P1/S1P/Gi	-0.03	0.095	-9999	-0.33	94	94
GNAO1	-0.018	0.13	-9999	-0.48	67	67
S1P/S1P3/G12/G13	-0.001	0.013	-9999	-10000	0	0
AKT1	-0.011	0.051	-9999	-0.68	4	4
AKT3	0.013	0.19	-9999	-1.4	19	19
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.003	0.048	-9999	-0.79	4	4
GNAI2	0.013	0.003	-9999	-10000	0	0
GNAI3	0.012	0.002	-9999	-10000	0	0
GNAI1	-0.033	0.19	-9999	-0.79	62	62
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.01	0.03	-9999	-0.3	10	10
S1PR2	0	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.01	0.11	-9999	-0.39	40	40
MAPK3	0.018	0.1	-9999	-0.51	14	14
MAPK1	0.018	0.1	-9999	-0.51	14	14
JAK2	0.02	0.1	-9999	-0.47	18	18
CXCR4	0.014	0.1	-9999	-0.48	19	19
FLT1	0.013	0.025	-9999	-0.8	1	1
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.017	0.1	-9999	-0.51	14	14
S1P/S1P3/Gi	0.009	0.11	-9999	-0.39	40	40
RAC1	0	0	-9999	-10000	0	0
RhoA/GTP	-0.026	0.084	-9999	-0.49	14	14
VEGFA	0.01	0.032	-9999	-0.3	12	12
S1P/S1P2/Gi	0.008	0.1	-9999	-0.37	39	39
VEGFR1 homodimer/VEGFA homodimer	0.021	0.03	-9999	-0.45	2	2
RHOA	0	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.007	0.042	-9999	-0.33	17	17
GNAQ	-0.002	0.041	-9999	-0.79	3	3
GNAZ	0.006	0.073	-9999	-0.79	9	9
G12/G13	0	0	-9999	-10000	0	0
GNA14	-0.013	0.085	-9999	-0.45	32	32
GNA15	-0.003	0.033	-9999	-0.36	8	8
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
GNA11	-0.002	0.041	-9999	-0.79	3	3
Rac1/GTP	-0.026	0.084	-9999	-0.49	14	14

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0	0	-9999	-10000	0	0
SPHK1	-0.007	0.052	-9999	-0.34	23	23
GNAI2	0	0	-9999	-10000	0	0
mol:S1P	0.02	0.019	-9999	-0.36	2	2
GNAO1	-0.03	0.13	-9999	-0.49	67	67
mol:Sphinganine-1-P	0.017	0.039	-9999	-0.6	2	2
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	-0.001	0.011	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
S1PR3	-0.003	0.028	-9999	-0.29	10	10
S1PR2	0	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.001	0.014	-9999	-0.31	2	2
S1PR5	-0.008	0.058	-9999	-0.35	25	25
S1PR4	-0.015	0.08	-9999	-0.36	46	46
GNAI1	-0.045	0.18	-9999	-0.79	62	62
S1P/S1P5/G12	-0.005	0.032	-9999	-0.46	3	3
S1P/S1P3/Gq	-0.005	0.037	-9999	-0.31	4	4
S1P/S1P4/Gi	-0.028	0.084	-9999	-0.33	42	42
GNAQ	-0.002	0.041	-9999	-0.79	3	3
GNAZ	-0.007	0.071	-9999	-0.79	9	9
GNA14	-0.013	0.085	-9999	-0.45	32	32
GNA15	-0.003	0.033	-9999	-0.36	8	8
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
GNA11	-0.002	0.041	-9999	-0.79	3	3
ABCC1	0	0	-9999	-10000	0	0

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0	0	-10000	0	-10000	0	0
mol:PIP3	-0.019	0.081	0.33	1	-0.36	57	58
FRAP1	0.01	0.022	-10000	0	-10000	0	0
AKT1	-0.016	0.07	0.24	1	-0.3	57	58
INSR	0	0.009	-10000	0	-0.29	1	1
Insulin Receptor/Insulin	0	0.005	-10000	0	-10000	0	0
mol:GTP	-0.013	0.055	-10000	0	-0.33	14	14
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.004	0.018	-10000	0	-10000	0	0
TSC2	0	0.002	-10000	0	-10000	0	0
RHEB/GDP	-0.011	0.047	-10000	0	-0.3	14	14
TSC1	0	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	-0.017	0.083	-10000	0	-0.42	45	45
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.005	0.021	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0	0	-10000	0	-10000	0	0
RPS6KB1	0.018	0.045	-10000	0	-0.25	14	14
MAP3K5	0.009	0.027	-10000	0	-0.44	4	4
PIK3R1	-0.009	0.086	-10000	0	-0.79	13	13
apoptosis	0.009	0.027	-10000	0	-0.44	4	4
mol:LY294002	0	0	-10000	0	-0.002	45	45
EIF4B	0.025	0.041	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.007	0.03	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	-0.001	0.008	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	-0.021	0.087	-10000	0	-0.38	58	58
mTOR/RHEB/GTP/Raptor/GBL	0.025	0.032	0.18	1	-10000	0	1
FKBP1A	0	0.009	-10000	0	-10000	0	0
RHEB/GTP	-0.011	0.047	-10000	0	-0.34	1	1
mol:Amino Acids	0	0	-10000	0	-0.002	45	45
FKBP12/Rapamycin	0	0.006	-10000	0	-10000	0	0
PDPK1	-0.017	0.074	0.26	1	-0.33	57	58
EIF4E	0	0	-10000	0	-10000	0	0
ASK1/PP5C	-0.004	0.039	-10000	0	-0.62	4	4
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.016	0.001	-10000	0	-10000	0	0
TSC1/TSC2	-0.014	0.058	-10000	0	-0.36	14	14
tumor necrosis factor receptor activity	0	0	0.002	45	-10000	0	45
RPS6	0	0	-10000	0	-10000	0	0
PPP5C	0	0	-10000	0	-10000	0	0
EIF4G1	0	0	-10000	0	-10000	0	0
IRS1	-0.011	0.09	-10000	0	-0.45	45	45
INS	0	0	-10000	0	-10000	0	0
PTEN	-0.001	0.034	-10000	0	-0.79	2	2
PDK2	-0.018	0.079	0.26	1	-0.34	60	61
EIF4EBP1	0.013	0.01	-10000	0	-10000	0	0
PIK3CA	0	0.009	-10000	0	-0.29	1	1
PPP2R5D	0.017	0.021	-10000	0	-10000	0	0
peptide biosynthetic process	0.016	0.005	-10000	0	-10000	0	0
RHEB	0	0	-10000	0	-10000	0	0
EIF4A1	0	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	0.003	2	-0.003	13	15
EEF2	0.016	0.005	-10000	0	-10000	0	0
eIF4E/4E-BP1	0	0	-10000	0	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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	0	-10000	0	-10000	0	0
NFATC1	0.049	0.029	-10000	0	-0.36	3	3
NFATC2	0.016	0.064	-10000	0	-0.31	11	11
NFATC3	0	0.015	-10000	0	-0.51	1	1
YWHAE	0	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.012	0.095	-10000	0	-0.4	38	38
Exportin 1/Ran/NUP214	0	0	-10000	0	-10000	0	0
mol:DAG	0	0.002	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.019	0.077	-10000	0	-0.49	18	18
BCL2/BAX	-0.021	0.11	-10000	0	-0.61	37	37
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.001	0.003	-10000	0	-10000	0	0
CaM/Ca2+	-0.001	0.003	-10000	0	-10000	0	0
BAX	-0.001	0.02	-10000	0	-0.29	5	5
MAPK14	0.011	0.003	-10000	0	-10000	0	0
BAD	0	0.009	-10000	0	-0.29	1	1
CABIN1/MEF2D	-0.02	0.081	-10000	0	-0.51	19	19
Calcineurin A alpha-beta B1/BCL2	-0.027	0.14	-10000	0	-0.79	37	37
FKBP8	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.02	0.08	0.5	19	-10000	0	19
KPNB1	0	0	-10000	0	-10000	0	0
KPNA2	-0.029	0.088	-10000	0	-0.29	108	108
XPO1	0	0	-10000	0	-10000	0	0
SFN	-0.016	0.099	-10000	0	-0.51	35	35
MAP3K8	0.004	0.073	-10000	0	-0.74	10	10
NFAT4/CK1 alpha	-0.001	0.016	-10000	0	-0.43	1	1
MEF2D/NFAT1/Cbp/p300	-0.036	0.09	-10000	0	-0.32	90	90
CABIN1	0.012	0.096	-10000	0	-0.4	38	38
CALM1	0.001	0.003	-10000	0	-10000	0	0
RAN	0	0	-10000	0	-10000	0	0
MAP3K1	-0.001	0.024	-10000	0	-0.79	1	1
CAMK4	-0.011	0.059	-10000	0	-0.31	39	39
mol:Ca2+	0	0.006	-10000	0	-10000	0	0
MAPK3	0	0	-10000	0	-10000	0	0
YWHAH	0	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.01	0.044	-10000	0	-0.6	1	1
YWHAB	0	0	-10000	0	-10000	0	0
MAPK8	0.005	0.068	-10000	0	-0.79	8	8
MAPK9	0	0	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
FKBP1A	0	0.009	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	-0.002	0.021	-10000	0	-0.4	1	1
PRKCH	-0.001	0.024	-10000	0	-0.79	1	1
CABIN1/Cbp/p300	-0.001	0.003	-10000	0	-10000	0	0
CASP3	0.011	0.003	-10000	0	-10000	0	0
PIM1	0	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0.005	-10000	0	-10000	0	0
apoptosis	-0.007	0.035	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	-0.003	0.024	-10000	0	-10000	0	0
PRKCB	-0.02	0.11	-10000	0	-0.55	39	39
PRKCE	0	0	-10000	0	-10000	0	0
JNK2/NFAT4	0	0.014	-10000	0	-0.46	1	1
BAD/BCL-XL	0	0.006	-10000	0	-10000	0	0
PRKCD	0	0.009	-10000	0	-0.29	1	1
NUP214	0	0	-10000	0	-10000	0	0
PRKCZ	0.01	0.024	-10000	0	-0.79	1	1
PRKCA	-0.021	0.12	-10000	0	-0.76	30	30
PRKCG	-0.013	0.061	-10000	0	-0.29	49	49
PRKCQ	-0.037	0.16	-10000	0	-0.69	59	59
FKBP38/BCL2	-0.02	0.11	-10000	0	-0.6	37	37
EP300	0	0.001	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0	0	-10000	0	-10000	0	0
NFATc/JNK1	0.048	0.047	-10000	0	-0.37	9	9
CaM/Ca2+/FKBP38	0	0	-10000	0	-10000	0	0
FKBP12/FK506	0	0.006	-10000	0	-10000	0	0
CSNK1A1	0.018	0.006	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.006	0.032	-10000	0	-0.53	1	1
NFATc/ERK1	0.054	0.027	-10000	0	-0.36	1	1
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.019	0.076	-10000	0	-0.48	18	18
NR4A1	-0.007	0.21	-10000	0	-0.7	90	90
GSK3B	0.011	0.003	-10000	0	-10000	0	0
positive T cell selection	0	0.015	-10000	0	-0.5	1	1
NFAT1/CK1 alpha	-0.015	0.039	-10000	0	-10000	0	0
RCH1/ KPNB1	-0.018	0.056	-10000	0	-10000	0	0
YWHAQ	0	0	-10000	0	-10000	0	0
PRKACA	0.011	0.003	-10000	0	-10000	0	0
AKAP5	-0.015	0.067	-10000	0	-0.3	54	54
MEF2D	0	0.001	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	-0.001	0.015	-10000	0	-0.29	3	3
NFATc/p38 alpha	0.051	0.03	-10000	0	-0.36	1	1
CREBBP	0	0.001	-10000	0	-10000	0	0
BCL2	-0.027	0.14	-10000	0	-0.79	37	37

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	-0.017	0.095	-9999	-0.58	30	30
KLHL20	-0.008	0.032	-9999	-0.24	3	3
CYFIP2	-0.01	0.066	-9999	-0.36	31	31
Rac1/GDP	0.05	0.067	-9999	-0.44	2	2
ENAH	-0.016	0.094	-9999	-0.57	30	30
AP1M1	0	0	-9999	-10000	0	0
RAP1B	0	0	-9999	-10000	0	0
RAP1A	0	0	-9999	-10000	0	0
CTNNB1	0	0	-9999	-10000	0	0
CDC42/GTP	-0.008	0.047	-9999	-0.49	1	1
ABI1/Sra1/Nap1	-0.006	0.024	-9999	-0.21	2	2
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.017	0.081	-9999	-0.47	32	32
RAPGEF1	0.039	0.088	-9999	-0.48	30	30
CTNND1	0	0.009	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.017	0.098	-9999	-0.6	30	30
CRK	0.031	0.095	-9999	-0.53	30	30
E-cadherin/gamma catenin/alpha catenin	-0.015	0.086	-9999	-0.52	31	31
alphaE/beta7 Integrin	-0.006	0.04	-9999	-0.6	2	2
IQGAP1	0	0	-9999	-10000	0	0
NCKAP1	0	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	-0.003	0.036	-9999	-0.48	6	6
DLG1	-0.016	0.094	-9999	-0.57	30	30
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.008	0.04	-9999	-0.31	2	2
MLLT4	-0.005	0.059	-9999	-0.72	7	7
ARF6/GTP/NME1/Tiam1	-0.007	0.029	-9999	-10000	0	0
PI3K	-0.011	0.051	-9999	-0.42	2	2
ARF6	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.017	0.1	-9999	-0.6	31	31
TIAM1	-0.001	0.018	-9999	-0.29	4	4
E-cadherin(dimer)/Ca2+	-0.012	0.073	-9999	-0.44	30	30
AKT1	-0.006	0.029	-9999	-0.24	1	1
PIK3R1	-0.009	0.086	-9999	-0.79	13	13
CDH1	-0.022	0.13	-9999	-0.79	30	30
RhoA/GDP	0.049	0.067	-9999	-0.52	1	1
actin cytoskeleton organization	-0.006	0.024	-9999	-0.18	3	3
CDC42/GDP	0.049	0.067	-9999	-0.52	1	1
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.01	0.055	-9999	-0.33	31	31
ITGB7	-0.01	0.058	-9999	-0.79	2	2
RAC1	0	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.013	0.077	-9999	-0.47	30	30
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.012	0.074	-9999	-0.45	30	30
mol:GDP	0.046	0.078	-9999	-0.41	30	30
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	-0.001	0.025	-9999	-0.54	2	2
p120 catenin/RhoA/GDP	-0.01	0.058	-9999	-0.54	1	1
RAC1/GTP/IQGAP1	0	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0
CTNNA1	0	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	-0.007	0.029	-9999	-0.22	7	7
NME1	-0.015	0.064	-9999	-0.29	55	55
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	-0.017	0.095	-9999	-0.57	31	31
regulation of cell-cell adhesion	-0.007	0.041	-9999	-0.42	1	1
WASF2	-0.003	0.012	-9999	-10000	0	0
Rap1/GTP	-0.01	0.054	-9999	-0.58	1	1
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.016	0.076	-9999	-0.44	33	33
CCND1	-0.009	0.036	-9999	-0.27	7	7
VAV2	0.035	0.092	-9999	-0.51	30	30
RAP1/GDP	-0.009	0.055	-9999	-0.56	1	1
adherens junction assembly	-0.016	0.091	-9999	-0.55	31	31
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0	0	-9999	-10000	0	0
PIP5K1C	0	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.015	0.072	-9999	-0.41	33	33
E-cadherin/beta catenin	-0.013	0.08	-9999	-0.49	30	30
mol:GTP	0	0	-9999	-10000	0	0
SRC	-0.016	0.094	-9999	-0.57	30	30
PIK3CA	0	0.009	-9999	-0.29	1	1
Rac1/GTP	-0.011	0.052	-9999	-0.4	3	3
E-cadherin/beta catenin/alpha catenin	-0.014	0.085	-9999	-0.52	30	30
ITGAE	0	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.017	0.1	-9999	-0.61	30	30

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	-0.002	0.028	-10000	0	-0.46	4	4
TRAF2/ASK1	-0.002	0.033	-10000	0	-0.53	4	4
ATM	0	0	-10000	0	-10000	0	0
MAP2K3	0.024	0.046	-10000	0	-0.44	2	2
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.025	0.064	-10000	0	-0.38	9	9
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	-0.038	0.099	-10000	0	-0.29	142	142
TXN	0.008	0.006	-10000	0	-10000	0	0
CALM1	0	0	-10000	0	-10000	0	0
GADD45A	0	0	-10000	0	-10000	0	0
GADD45B	0	0	-10000	0	-10000	0	0
MAP3K1	-0.001	0.024	-10000	0	-0.79	1	1
MAP3K6	-0.001	0.024	-10000	0	-0.79	1	1
MAP3K7	0	0.009	-10000	0	-0.29	1	1
MAP3K4	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	-0.003	0.041	-10000	0	-0.6	5	5
TAK1/TAB family	0.001	0.011	0.21	3	-10000	0	3
RAC1/OSM/MEKK3	0	0.005	-10000	0	-10000	0	0
TRAF2	-0.001	0.018	-10000	0	-0.29	4	4
RAC1/OSM/MEKK3/MKK3	-0.007	0.023	-10000	0	-0.4	1	1
TRAF6	0.008	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.068	0.21	-10000	0	-0.59	126	126
CCM2	-0.001	0.013	-10000	0	-0.29	2	2
CaM/Ca2+/CAMKIIB	-0.044	0.14	-10000	0	-0.53	76	76
MAPK11	-0.002	0.041	-10000	0	-0.79	3	3
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.041	0.13	-10000	0	-0.48	79	79
OSM/MEKK3	0	0.008	-10000	0	-10000	0	0
TAOK1	-0.006	0.099	-10000	0	-0.44	55	55
TAOK2	0.017	0	-10000	0	-10000	0	0
TAOK3	0.017	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0	0	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	-0.003	0.048	-10000	0	-0.79	4	4
MAP3K10	0	0.009	-10000	0	-0.29	1	1
MAP3K3	0	0	-10000	0	-10000	0	0
TRX/ASK1	-0.002	0.032	-10000	0	-0.52	4	4
GADD45/MTK1/MTK1	-0.014	0.037	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	-0.006	0.051	-10000	0	-0.47	13	13
HDAC3	0	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0.012	-10000	0	-0.4	1	1
GATA1/HDAC4	-0.004	0.03	-10000	0	-0.6	1	1
GATA1/HDAC5	-0.003	0.024	-10000	0	-10000	0	0
GATA2/HDAC5	-0.018	0.097	-10000	0	-0.6	28	28
HDAC5/BCL6/BCoR	-0.004	0.044	-10000	0	-0.52	8	8
HDAC9	-0.01	0.081	-10000	0	-0.52	22	22
Glucocorticoid receptor/Hsp90/HDAC6	-0.007	0.06	-10000	0	-0.52	15	15
HDAC4/ANKRA2	-0.001	0.018	-10000	0	-0.6	1	1
HDAC5/YWHAB	0	0	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0	0.001	-10000	0	-10000	0	0
GATA2	-0.024	0.13	-10000	0	-0.62	42	42
HDAC4/RFXANK	-0.002	0.023	-10000	0	-0.6	1	1
BCOR	-0.001	0.034	-10000	0	-0.79	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	-0.001	0.013	-10000	0	-0.29	2	2
HDAC5	0	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.007	0.065	-10000	0	-0.6	13	13
Histones	-0.003	0.026	-10000	0	-10000	0	0
ADRBK1	0	0	-10000	0	-10000	0	0
HDAC4	-0.001	0.024	-10000	0	-0.79	1	1
XPO1	0	0	-10000	0	-10000	0	0
HDAC5/ANKRA2	0	0	-10000	0	-10000	0	0
HDAC4/Ubc9	-0.001	0.018	-10000	0	-0.6	1	1
HDAC7	0	0	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0	0	-10000	0	-10000	0	0
TUBA1B	0	0	-10000	0	-10000	0	0
HDAC6	0	0	-10000	0	-10000	0	0
HDAC5/RFXANK	-0.001	0.014	-10000	0	-10000	0	0
CAMK4	-0.011	0.059	-10000	0	-0.31	39	39
Tubulin/HDAC6	-0.001	0.017	-10000	0	-0.52	1	1
SUMO1	0	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0	0	-10000	0	-10000	0	0
GATA1	-0.005	0.037	-10000	0	-0.29	18	18
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0
NR3C1	-0.011	0.092	-10000	0	-0.79	15	15
SUMO1/HDAC4	0	0.013	-10000	0	-0.43	1	1
SRF	0	0	-10000	0	-10000	0	0
HDAC4/YWHAB	-0.001	0.018	-10000	0	-0.6	1	1
Tubulin	-0.001	0.02	-10000	0	-0.6	1	1
HDAC4/14-3-3 E	-0.001	0.018	-10000	0	-0.6	1	1
GNB1	0	0	-10000	0	-10000	0	0
RANGAP1	0	0.009	-10000	0	-10000	0	0
BCL6/BCoR	-0.004	0.051	-10000	0	-0.6	8	8
HDAC4/HDAC3/SMRT (N-CoR2)	0	0.016	-10000	0	-0.52	1	1
HDAC4/SRF	-0.006	0.034	-10000	0	-0.52	2	2
HDAC4/ER alpha	-0.11	0.22	-10000	0	-0.6	168	168
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	-0.003	0.025	-10000	0	-10000	0	0
cell motility	-0.001	0.017	-10000	0	-0.52	1	1
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0	0	-10000	0	-10000	0	0
HDAC7/HDAC3	0	0	-10000	0	-10000	0	0
BCL6	-0.004	0.058	-10000	0	-0.79	6	6
HDAC4/CaMK II delta B	-0.001	0.024	-10000	0	-0.79	1	1
Hsp90/HDAC6	0	0.006	-10000	0	-10000	0	0
ESR1	-0.15	0.28	-10000	0	-0.58	291	291
HDAC6/HDAC11	-0.001	0.01	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0	0	-10000	0	-10000	0	0
NPC	0	0	-10000	0	-10000	0	0
MEF2C	-0.001	0.024	-10000	0	-0.79	1	1
RAN	0	0	-10000	0	-10000	0	0
HDAC4/MEF2C	-0.001	0.019	-10000	0	-0.44	2	2
GNG2	-0.009	0.086	-10000	0	-0.79	13	13
NCOR2	0	0	-10000	0	-10000	0	0
TUBB2A	-0.001	0.027	-10000	0	-0.46	3	3
HDAC11	-0.001	0.015	-10000	0	-0.29	3	3
HSP90AA1	0	0.009	-10000	0	-0.29	1	1
RANBP2	0	0	-10000	0	-10000	0	0
ANKRA2	0	0	-10000	0	-10000	0	0
RFXANK	-0.002	0.022	-10000	0	-0.29	6	6
nuclear import	0	0.013	0.43	1	-10000	0	1

×

Paxillin-independent events mediated by a4b1 and a4b7

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.004	0.024	-9999	-0.4	2	2
CRKL	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0	0	-9999	-10000	0	0
ITGA4	-0.003	0.028	-9999	-0.29	10	10
alpha4/beta7 Integrin/MAdCAM1	-0.01	0.043	-9999	-0.45	3	3
EPO	-0.048	0.11	-9999	-0.29	177	177
alpha4/beta7 Integrin	-0.008	0.046	-9999	-0.45	6	6
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.002	0.018	-9999	-10000	0	0
EPO/EPOR (dimer)	-0.03	0.069	-9999	-10000	0	0
lamellipodium assembly	-0.004	0.044	-9999	-0.4	13	13
PIK3CA	0	0.009	-9999	-0.29	1	1
PI3K	-0.007	0.066	-9999	-0.6	13	13
ARF6	0	0	-9999	-10000	0	0
JAK2	-0.01	0.025	-9999	-0.5	1	1
PXN	0	0	-9999	-10000	0	0
PIK3R1	-0.009	0.086	-9999	-0.79	13	13
MADCAM1	-0.012	0.057	-9999	-0.29	43	43
cell adhesion	-0.01	0.043	-9999	-0.45	3	3
CRKL/CBL	0	0	-9999	-10000	0	0
ITGB1	0	0	-9999	-10000	0	0
SRC	0.025	0.057	-9999	-0.47	13	13
ITGB7	-0.01	0.058	-9999	-0.79	2	2
RAC1	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.008	0.059	-9999	-0.52	13	13
p130Cas/Crk/Dock1	-0.006	0.043	-9999	-10000	0	0
VCAM1	-0.011	0.088	-9999	-0.63	19	19
RHOA	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.002	0.014	-9999	-10000	0	0
BCAR1	0.034	0.054	-9999	-0.43	13	13
EPOR	0	0.009	-9999	-0.29	1	1
mol:GDP	0	0	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
GIT1	-0.001	0.02	-9999	-0.29	5	5
Rac1/GTP	-0.004	0.046	-9999	-0.42	13	13

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.022	0.11	-9999	-0.6	38	38
AKT1	0.08	0.069	-9999	-0.68	6	6
PTK2B	0.035	0.12	-9999	-0.51	39	39
VEGFR2 homodimer/Frs2	-0.008	0.078	-9999	-0.8	9	9
CAV1	-0.17	0.33	-9999	-0.79	238	238
CALM1	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.008	0.073	-9999	-0.74	9	9
endothelial cell proliferation	0.082	0.084	-9999	-0.68	6	6
mol:Ca2+	0.05	0.07	-9999	-0.87	5	5
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.007	0.069	-9999	-0.7	9	9
RP11-342D11.1	0.042	0.07	-9999	-0.66	9	9
CDH5	-0.007	0.071	-9999	-0.79	9	9
VEGFA homodimer	-0.001	0.012	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
SHC2	-0.02	0.12	-9999	-0.77	28	28
HRAS/GDP	-0.006	0.056	-9999	-0.76	5	5
SH2D2A	-0.035	0.1	-9999	-0.3	126	126
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.003	0.052	-9999	-0.68	5	5
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.02	0.084	-9999	-0.69	12	12
VEGFR1 homodimer	-0.001	0.024	-9999	-0.79	1	1
SHC/GRB2/SOS1	-0.004	0.062	-9999	-0.84	5	5
GRB10	0.05	0.07	-9999	-0.87	5	5
PTPN11	0	0	-9999	-10000	0	0
GRB2	0	0.009	-9999	-0.29	1	1
PAK1	-0.007	0.044	-9999	-0.29	25	25
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.008	0.089	-9999	-0.78	11	11
HRAS	-0.002	0.027	-9999	-0.29	9	9
VEGF/Rho/ROCK1/Integrin Complex	-0.011	0.063	-9999	-0.55	8	8
HIF1A	0	0	-9999	-10000	0	0
FRS2	-0.003	0.029	-9999	-0.29	11	11
oxygen and reactive oxygen species metabolic process	-0.007	0.067	-9999	-0.68	9	9
mol:GTP	0	0	-9999	-10000	0	0
FLT4	-0.002	0.041	-9999	-0.79	3	3
Nck/Pak	-0.004	0.028	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.008	0.08	-9999	-0.77	10	10
mol:GDP	-0.004	0.059	-9999	-0.8	5	5
mol:NADP	0.073	0.05	-9999	-0.55	5	5
eNOS/Hsp90	0.075	0.047	-9999	-0.51	5	5
PIK3R1	-0.009	0.086	-9999	-0.79	13	13
mol:IP3	0.051	0.072	-9999	-0.89	5	5
HIF1A/ARNT	0	0	-9999	-10000	0	0
SHB	-0.001	0.025	-9999	-0.79	1	1
VEGFA	-0.003	0.03	-9999	-0.29	12	12
VEGFC	0	0	-9999	-10000	0	0
FAK1/Vinculin	0.056	0.099	-9999	-0.88	7	7
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.022	0.12	-9999	-0.54	42	42
PTPN6	-0.001	0.013	-9999	-0.29	2	2
EPAS1	-0.006	0.07	-9999	-0.72	9	9
mol:L-citrulline	0.073	0.05	-9999	-0.55	5	5
ITGAV	0	0	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-0.29	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.008	0.07	-9999	-0.7	9	9
VEGFR2 homodimer/VEGFA homodimer	-0.007	0.072	-9999	-0.73	9	9
VEGFR2/3 heterodimer	-0.008	0.088	-9999	-0.86	10	10
VEGFB	0	0	-9999	-10000	0	0
MAPK11	0.055	0.076	-9999	-0.7	9	9
VEGFR2 homodimer	0.028	0.089	-9999	-0.89	9	9
FLT1	-0.001	0.024	-9999	-0.79	1	1
NEDD4	0	0	-9999	-10000	0	0
MAPK3	0.051	0.08	-9999	-0.84	6	6
MAPK1	0.051	0.08	-9999	-0.84	6	6
VEGFA145/NRP2	-0.004	0.039	-9999	-0.65	3	3
VEGFR1/2 heterodimer	-0.007	0.083	-9999	-0.85	9	9
KDR	0.028	0.09	-9999	-0.9	9	9
VEGFA165/NRP1/VEGFR2 homodimer	-0.006	0.079	-9999	-0.73	10	10
SRC	0	0.009	-9999	-0.29	1	1
platelet activating factor biosynthetic process	0.053	0.081	-9999	-0.87	6	6
PI3K	-0.008	0.073	-9999	-0.88	6	6
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.007	0.073	-9999	-0.74	9	9
FES	0.049	0.077	-9999	-0.62	12	12
GAB1	-0.005	0.068	-9999	-0.93	5	5
VEGFR2 homodimer/VEGFA homodimer/Src	-0.007	0.073	-9999	-0.74	9	9
CTNNB1	0	0	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
ARNT	0	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.009	0.17	-9999	-0.54	16	16
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.008	0.074	-9999	-0.71	10	10
PI3K/GAB1	0.079	0.077	-9999	-0.71	6	6
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.002	0.068	-9999	-0.89	5	5
PRKACA	0	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.007	0.083	-9999	-0.8	10	10
HSP90AA1	0	0.009	-9999	-0.29	1	1
CDC42	0.051	0.073	-9999	-0.68	9	9
actin cytoskeleton reorganization	-0.02	0.083	-9999	-0.68	12	12
PTK2	0.052	0.11	-9999	-0.82	10	10
EDG1	0.042	0.07	-9999	-0.66	9	9
mol:DAG	0.051	0.072	-9999	-0.89	5	5
CaM/Ca2+	-0.006	0.06	-9999	-0.81	5	5
MAP2K3	0.056	0.076	-9999	-0.85	5	5
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.005	0.069	-9999	-0.93	5	5
PLCG1	0.051	0.073	-9999	-0.91	5	5
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.007	0.07	-9999	-0.67	10	10
IQGAP1	0	0	-9999	-10000	0	0
YES1	-0.001	0.024	-9999	-0.79	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.007	0.073	-9999	-0.74	9	9
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.007	0.073	-9999	-0.74	9	9
cell migration	0.078	0.088	-9999	-0.79	6	6
mol:PI-3-4-5-P3	-0.007	0.065	-9999	-0.78	6	6
FYN	-0.001	0.034	-9999	-0.79	2	2
VEGFB/NRP1	-0.006	0.061	-9999	-0.62	9	9
mol:NO	0.073	0.05	-9999	-0.55	5	5
PXN	0	0	-9999	-10000	0	0
HRAS/GTP	-0.006	0.056	-9999	-0.76	5	5
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.005	0.069	-9999	-0.93	5	5
VHL	0	0	-9999	-10000	0	0
ITGB3	-0.029	0.15	-9999	-0.74	42	42
NOS3	0.075	0.056	-9999	-0.64	5	5
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.019	0.1	-9999	-0.53	36	36
RAC1	0	0	-9999	-10000	0	0
PRKCA	0.046	0.1	-9999	-0.97	5	5
PRKCB	0.047	0.1	-9999	-0.89	7	7
VCL	0	0	-9999	-10000	0	0
VEGFA165/NRP1	-0.007	0.065	-9999	-0.67	9	9
VEGFR1/2 heterodimer/VEGFA homodimer	-0.008	0.078	-9999	-0.79	9	9
VEGFA165/NRP2	-0.004	0.039	-9999	-0.65	3	3
MAPKKK cascade	-0.004	0.056	-9999	-0.76	5	5
NRP2	-0.002	0.042	-9999	-0.66	4	4
VEGFC homodimer	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
ROCK1	-0.001	0.024	-9999	-0.79	1	1
FAK1/Paxillin	0.056	0.099	-9999	-0.88	7	7
MAP3K13	0.049	0.08	-9999	-0.59	14	14
PDPK1	0.073	0.066	-9999	-0.66	6	6

×

IFN-gamma 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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.01	0.034	-9999	-0.41	2	2
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
CRKL	0	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	-0.007	0.028	-9999	-10000	0	0
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0	0.022	-9999	-0.52	2	2
antigen processing and presentation of peptide antigen via MHC class I	-0.006	0.039	-9999	-0.33	2	2
CaM/Ca2+	0.009	0.031	-9999	-0.38	2	2
RAP1A	0	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.011	0.036	-9999	-0.39	2	2
AKT1	-0.011	0.046	-9999	-0.45	2	2
MAP2K1	0.04	0.044	-9999	-0.38	2	2
MAP3K11	0.03	0.043	-9999	-0.38	2	2
IFNGR1	0.012	0.003	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.024	0.094	-9999	-0.41	24	24
Rap1/GTP	-0.004	0.015	-9999	-10000	0	0
CRKL/C3G	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.013	0.036	-9999	-0.43	2	2
CEBPB	0.075	0.039	-9999	-0.4	1	1
STAT3	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.007	0.055	-9999	-1.2	1	1
STAT1	-0.011	0.036	-9999	-0.38	2	2
CALM1	0	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.03	0.1	-9999	-0.28	150	150
PIK3CA	0	0.009	-9999	-0.29	1	1
STAT1 (dimer)/PIAS1	-0.01	0.032	-9999	-0.37	1	1
CEBPB/PTGES2/Cbp/p300	-0.001	0.012	-9999	-10000	0	0
mol:Ca2+	0.005	0.034	-9999	-0.41	2	2
MAPK3	0.054	0.04	-9999	-0.43	1	1
STAT1 (dimer)	-0.006	0.054	-9999	-0.48	2	2
MAPK1	0.054	0.04	-9999	-10000	0	0
JAK2	0.011	0.024	-9999	-0.79	1	1
PIK3R1	-0.009	0.086	-9999	-0.79	13	13
JAK1	0.011	0.024	-9999	-0.78	1	1
CAMK2D	-0.002	0.041	-9999	-0.79	3	3
DAPK1	0.07	0.033	-9999	-10000	0	0
SMAD7	0.05	0.038	-9999	-10000	0	0
CBL/CRKL/C3G	-0.007	0.022	-9999	-10000	0	0
PI3K	0.003	0.053	-9999	-0.41	14	14
IFNG	-0.03	0.1	-9999	-0.29	150	150
apoptosis	0.053	0.029	-9999	-10000	0	0
CAMK2G	0	0	-9999	-10000	0	0
STAT3 (dimer)	0	0	-9999	-10000	0	0
CAMK2A	-0.01	0.053	-9999	-0.29	37	37
CAMK2B	-0.068	0.21	-9999	-0.59	126	126
FRAP1	0.038	0.057	-9999	-0.42	2	2
PRKCD	-0.011	0.046	-9999	-0.39	8	8
RAP1B	0	0	-9999	-10000	0	0
negative regulation of cell growth	-0.006	0.039	-9999	-0.33	2	2
PTPN2	0	0	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
IRF1	0.064	0.047	-9999	-10000	0	0
STAT1 (dimer)/PIASy	-0.01	0.033	-9999	-0.37	1	1
SOCS1	0	0.049	-9999	-1.5	1	1
mol:GDP	-0.007	0.021	-9999	-10000	0	0
CASP1	0.049	0.045	-9999	-0.35	5	5
PTGES2	0	0.009	-9999	-0.29	1	1
IRF9	0.058	0.019	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.012	0.049	-9999	-0.4	14	14
RAP1/GDP	-0.004	0.016	-9999	-10000	0	0
CBL	0.027	0.043	-9999	-0.38	2	2
MAP3K1	0.031	0.045	-9999	-0.4	3	3
PIAS1	0	0	-9999	-10000	0	0
PIAS4	0	0.002	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.006	0.039	-9999	-0.33	2	2
PTPN11	0.02	0.045	-9999	-0.41	2	2
CREBBP	0	0	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	-0.006	0.055	-9999	-0.44	14	14
Caspase 8 (4 units)	-0.009	0.047	-9999	-0.99	1	1
NEF	-0.006	0.028	-9999	-0.22	11	11
NFKBIA	-0.001	0.011	-9999	-10000	0	0
BIRC3	0.035	0.081	-9999	-0.79	9	9
CYCS	0.04	0.06	-9999	-0.94	1	1
RIPK1	0	0	-9999	-10000	0	0
CD247	-0.025	0.12	-9999	-0.69	30	30
MAP2K7	0.042	0.049	-9999	-0.81	1	1
protein ubiquitination	0.066	0.034	-9999	-10000	0	0
CRADD	0	0	-9999	-10000	0	0
DAXX	0	0	-9999	-10000	0	0
FAS	-0.004	0.053	-9999	-0.79	5	5
BID	0.033	0.063	-9999	-1	1	1
NF-kappa-B/RelA/I kappa B alpha	-0.004	0.033	-9999	-0.33	9	9
TRADD	0	0	-9999	-10000	0	0
MAP3K5	-0.003	0.048	-9999	-0.79	4	4
CFLAR	0	0	-9999	-10000	0	0
FADD	-0.004	0.035	-9999	-0.29	16	16
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.004	0.033	-9999	-0.33	9	9
MAPK8	0.045	0.062	-9999	-0.47	9	9
APAF1	0	0	-9999	-10000	0	0
TRAF1	-0.001	0.015	-9999	-0.29	3	3
TRAF2	-0.001	0.018	-9999	-0.29	4	4
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.012	0.057	-9999	-0.33	23	23
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	-0.002	0.031	-9999	-0.39	1	1
CHUK	0.068	0.035	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.005	0.048	-9999	-0.51	8	8
TCRz/NEF	-0.025	0.11	-9999	-0.51	41	41
TNF	-0.016	0.096	-9999	-0.46	38	38
FASLG	-0.007	0.15	-9999	-0.66	41	41
NFKB1	-0.001	0.011	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.013	0.069	-9999	-0.53	17	17
CASP6	-0.004	0.032	-9999	-0.7	1	1
CASP7	0.073	0.076	-9999	-0.62	9	9
RELA	-0.001	0.011	-9999	-10000	0	0
CASP2	0	0	-9999	-10000	0	0
CASP3	0.073	0.076	-9999	-0.62	9	9
TNFRSF1A	0	0	-9999	-10000	0	0
TNFR1A/BAG4	-0.004	0.04	-9999	-0.6	4	4
CASP8	0	0	-9999	-10000	0	0
CASP9	0	0	-9999	-10000	0	0
MAP3K14	0.063	0.038	-9999	-10000	0	0
APAF-1/Caspase 9	-0.009	0.053	-9999	-0.5	9	9
BCL2	0.037	0.1	-9999	-0.42	43	43

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	-0.001	0.027	-9999	-0.9	1	1
VEGFR1 homodimer/NRP1	-0.001	0.027	-9999	-0.9	1	1
mol:DAG	0.038	0.032	-9999	-0.64	2	2
VEGFR1 homodimer/NRP1/VEGFR 121	-0.002	0.028	-9999	-0.84	1	1
CaM/Ca2+	-0.002	0.028	-9999	-0.6	2	2
HIF1A	0	0.011	-9999	-0.38	1	1
GAB1	0	0	-9999	-10000	0	0
AKT1	-0.006	0.051	-9999	-0.71	1	1
PLCG1	0.038	0.032	-9999	-0.64	2	2
NOS3	0.061	0.033	-9999	-0.55	2	2
CBL	0	0	-9999	-10000	0	0
mol:NO	0.061	0.032	-9999	-0.53	2	2
FLT1	0.029	0.031	-9999	-1	1	1
PGF	-0.002	0.031	-9999	-0.79	1	1
VEGFR1 homodimer/NRP2/VEGFR121	-0.003	0.046	-9999	-0.78	3	3
CALM1	0	0	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-0.29	1	1
eNOS/Hsp90	0.065	0.03	-9999	-0.64	1	1
endothelial cell proliferation	0.036	0.088	-9999	-0.58	7	7
mol:Ca2+	0.038	0.031	-9999	-0.63	2	2
MAPK3	0.039	0.081	-9999	-0.43	28	28
MAPK1	0.039	0.081	-9999	-1.1	1	1
PIK3R1	-0.009	0.086	-9999	-0.79	13	13
PLGF homodimer	-0.002	0.031	-9999	-0.79	1	1
PRKACA	0	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.17	0.33	-9999	-0.79	238	238
VEGFA homodimer	-0.003	0.031	-9999	-0.29	12	12
VEGFR1 homodimer/VEGFA homodimer	-0.002	0.031	-9999	-0.9	1	1
platelet activating factor biosynthetic process	0.046	0.079	-9999	-1.1	1	1
PI3K	-0.007	0.055	-9999	-0.46	15	15
PRKCA	0.033	0.085	-9999	-0.46	29	29
PRKCB	0.034	0.077	-9999	-0.47	21	21
VEGFR1 homodimer/PLGF homodimer	-0.002	0.033	-9999	-0.7	2	2
VEGFA	-0.003	0.031	-9999	-0.29	12	12
VEGFB	0	0	-9999	-10000	0	0
mol:IP3	0.038	0.032	-9999	-0.64	2	2
RASA1	0.039	0.026	-9999	-0.83	1	1
NRP2	-0.002	0.042	-9999	-0.66	4	4
VEGFR1 homodimer	0.029	0.031	-9999	-1	1	1
VEGFB homodimer	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.029	0.18	-9999	-0.59	8	8
PTPN11	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.007	0.054	-9999	-0.45	15	15
mol:L-citrulline	0.061	0.032	-9999	-0.53	2	2
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.002	0.027	-9999	-0.79	1	1
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.002	0.028	-9999	-0.84	1	1
CD2AP	0	0.009	-9999	-0.29	1	1
PI3K/GAB1	-0.006	0.052	-9999	-0.43	15	15
PDPK1	-0.006	0.05	-9999	-0.42	15	15
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.002	0.028	-9999	-0.84	1	1
mol:NADP	0.061	0.032	-9999	-0.53	2	2
HSP90AA1	0	0.009	-9999	-0.29	1	1
ubiquitin-dependent protein catabolic process	-0.002	0.026	-9999	-0.78	1	1
VEGFR1 homodimer/NRP2	-0.002	0.046	-9999	-0.79	3	3

×

EPO signaling pathway

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
BCL2L1	0.058	0.076	-9999	-0.52	1	1
CRKL	0.028	0.05	-9999	-0.48	1	1
mol:DAG	-0.007	0.026	-9999	-0.39	1	1
HRAS	-0.006	0.022	-9999	-0.39	1	1
MAPK8	0.011	0.068	-9999	-0.51	8	8
RAP1A	0.028	0.05	-9999	-0.48	1	1
GAB1	0.028	0.05	-9999	-0.48	1	1
MAPK14	0.015	0.052	-9999	-10000	0	0
EPO	-0.036	0.11	-9999	-0.29	177	177
PLCG1	-0.008	0.026	-9999	-0.4	1	1
EPOR/TRPC2/IP3 Receptors	0.012	0.01	-9999	-0.28	1	1
RAPGEF1	0	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.024	0.065	-9999	-0.62	6	6
GAB1/SHC/GRB2/SOS1	-0.008	0.022	-9999	-0.41	1	1
EPO/EPOR (dimer)	-0.027	0.067	-9999	-10000	0	0
IRS2	0.009	0.11	-9999	-0.46	46	46
STAT1	0.048	0.057	-9999	-0.5	1	1
STAT5B	-0.004	0.043	-9999	-0.43	4	4
cell proliferation	0.02	0.064	-9999	-0.47	8	8
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.01	0.043	-9999	-0.42	5	5
TEC	0.027	0.056	-9999	-0.48	4	4
SOCS3	-0.004	0.058	-9999	-0.79	6	6
STAT1 (dimer)	0.048	0.056	-9999	-0.49	1	1
JAK2	0.011	0.025	-9999	-0.8	1	1
PIK3R1	-0.009	0.086	-9999	-0.79	13	13
EPO/EPOR (dimer)/JAK2	0.054	0.04	-9999	-0.51	1	1
EPO/EPOR	-0.027	0.067	-9999	-10000	0	0
LYN	0.013	0.002	-9999	-10000	0	0
TEC/VAV2	0.034	0.055	-9999	-0.46	4	4
elevation of cytosolic calcium ion concentration	0.012	0.01	-9999	-0.28	1	1
SHC1	0	0	-9999	-10000	0	0
EPO/EPOR (dimer)/LYN	-0.017	0.05	-9999	-10000	0	0
mol:IP3	-0.007	0.026	-9999	-0.39	1	1
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.03	0.094	-9999	-0.41	59	59
SH2B3	0.012	0.004	-9999	-10000	0	0
NFKB1	0.015	0.052	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2/SOCS3	-0.01	0.031	-9999	-0.32	7	7
PTPN6	0.021	0.052	-9999	-0.51	1	1
TEC/VAV2/GRB2	-0.011	0.034	-9999	-0.44	4	4
EPOR	0.012	0.01	-9999	-0.28	1	1
INPP5D	0	0	-9999	-10000	0	0
mol:GDP	-0.008	0.022	-9999	-0.42	1	1
SOS1	0	0	-9999	-10000	0	0
PLCG2	-0.002	0.035	-9999	-0.79	2	2
CRKL/CBL/C3G	-0.009	0.025	-9999	-0.44	1	1
VAV2	0.028	0.05	-9999	-0.48	1	1
CBL	0.028	0.05	-9999	-0.48	1	1
SHC/Grb2/SOS1	0.004	0.028	-9999	-0.44	1	1
STAT5A	-0.006	0.055	-9999	-0.47	9	9
GRB2	0	0.009	-9999	-0.29	1	1
STAT5 (dimer)	0.058	0.085	-9999	-0.56	5	5
LYN/PLCgamma2	-0.001	0.026	-9999	-0.6	2	2
PTPN11	0	0	-9999	-10000	0	0
BTK	0.028	0.051	-9999	-0.48	1	1
BCL2	0.036	0.19	-9999	-0.98	37	37

×

HIF-2-alpha transcription factor network

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
MMP14	0	0.017	-10000	0	-10000	0	0
oxygen homeostasis	0.012	0.012	-10000	0	-10000	0	0
TCEB2	-0.007	0.045	-10000	0	-0.29	26	26
TCEB1	-0.001	0.013	-10000	0	-0.29	2	2
VHL/Elongin B/Elongin C/HIF2A	-0.006	0.038	-10000	0	-0.43	2	2
EPO	0.14	0.15	-10000	0	-0.65	3	3
FIH (dimer)	0.023	0.012	-10000	0	-10000	0	0
APEX1	0.022	0.014	-10000	0	-0.31	1	1
SERPINE1	0.16	0.16	-10000	0	-0.67	5	5
FLT1	-0.003	0.079	-10000	0	-1.1	5	5
ADORA2A	0.14	0.16	-10000	0	-0.64	5	5
germ cell development	0.16	0.15	-10000	0	-0.65	6	6
SLC11A2	0.16	0.15	-10000	0	-0.68	4	4
BHLHE40	0.16	0.16	-10000	0	-0.81	5	5
HIF1AN	0.023	0.012	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	0.012	0.07	-10000	0	-0.42	5	5
ETS1	0.023	0.056	-10000	0	-0.8	5	5
CITED2	0.001	0.01	-10000	0	-10000	0	0
KDR	-0.006	0.11	-10000	0	-1.2	8	8
PGK1	0.16	0.15	-10000	0	-0.68	4	4
SIRT1	0	0	-10000	0	-10000	0	0
response to hypoxia	-0.001	0.003	-10000	0	-10000	0	0
HIF2A/ARNT	0.18	0.16	-10000	0	-0.77	5	5
EPAS1	0.091	0.084	-10000	0	-0.41	5	5
SP1	0.019	0.002	-10000	0	-10000	0	0
ABCG2	0.12	0.25	-10000	0	-0.69	79	79
EFNA1	0.16	0.15	-10000	0	-0.68	4	4
FXN	0.15	0.15	-10000	0	-0.66	4	4
POU5F1	0.16	0.16	-10000	0	-0.68	6	6
neuron apoptosis	-0.17	0.16	0.74	5	-10000	0	5
EP300	0	0	-10000	0	-10000	0	0
EGLN3	0	0.084	-10000	0	-0.29	81	81
EGLN2	0.021	0.026	-10000	0	-0.3	3	3
EGLN1	0.022	0.028	-10000	0	-0.8	1	1
VHL/Elongin B/Elongin C	-0.004	0.023	-10000	0	-10000	0	0
VHL	0	0	-10000	0	-10000	0	0
ARNT	0.023	0.01	-10000	0	-10000	0	0
SLC2A1	0.15	0.16	-10000	0	-0.64	6	6
TWIST1	0.13	0.21	-10000	0	-0.69	45	45
ELK1	0.019	0.009	-10000	0	-0.29	1	1
HIF2A/ARNT/Cbp/p300	0.008	0.063	-10000	0	-0.48	2	2
VEGFA	0.16	0.15	-10000	0	-0.71	4	4
CREBBP	0	0	-10000	0	-10000	0	0

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.001	0.024	0.3	2	-0.36	3	5
DAPP1	0.036	0.053	-10000	0	-0.58	4	4
Src family/SYK family/BLNK-LAT/BTK-ITK	0.046	0.078	-10000	0	-0.56	10	10
mol:DAG	0.052	0.05	0.21	1	-0.27	7	8
HRAS	0.009	0.027	-10000	0	-0.29	9	9
RAP1A	0	0	-10000	0	-10000	0	0
ARF5/GDP	0.038	0.032	-10000	0	-0.26	4	4
PLCG2	-0.002	0.035	-10000	0	-0.79	2	2
PLCG1	0	0	-10000	0	-10000	0	0
ARF5	0	0.009	-10000	0	-0.29	1	1
mol:GTP	-0.001	0.022	0.26	2	-0.39	2	4
ARF1/GTP	-0.001	0.022	0.28	2	-0.37	2	4
RHOA	0	0	-10000	0	-10000	0	0
YES1	-0.001	0.024	-10000	0	-0.79	1	1
RAP1A/GTP	-0.001	0.022	0.25	2	-0.38	2	4
ADAP1	-0.003	0.032	0.26	2	-0.39	5	7
ARAP3	-0.001	0.022	0.26	2	-0.39	2	4
INPPL1	0	0	-10000	0	-10000	0	0
PREX1	-0.01	0.057	-10000	0	-0.31	36	36
ARHGEF6	-0.011	0.092	-10000	0	-0.79	15	15
ARHGEF7	0	0	-10000	0	-10000	0	0
ARF1	0	0	-10000	0	-10000	0	0
NRAS	0.011	0.013	-10000	0	-0.29	2	2
FYN	-0.001	0.034	-10000	0	-0.79	2	2
ARF6	0	0	-10000	0	-10000	0	0
FGR	-0.001	0.025	-10000	0	-0.54	2	2
mol:Ca2+	0.039	0.029	-10000	0	-10000	0	0
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	-0.001	0.018	-10000	0	-0.29	4	4
ZAP70	-0.031	0.12	-10000	0	-0.79	20	20
mol:IP3	0.047	0.038	-10000	0	-0.22	1	1
LYN	0	0	-10000	0	-10000	0	0
ARF1/GDP	0.038	0.032	-10000	0	-0.3	2	2
RhoA/GDP	-0.002	0.022	0.27	2	-10000	0	2
PDK1/Src/Hsp90	0	0.006	-10000	0	-10000	0	0
BLNK	0	0	-10000	0	-10000	0	0
actin cytoskeleton reorganization	0.061	0.034	-10000	0	-10000	0	0
SRC	0	0.009	-10000	0	-0.29	1	1
PLEKHA2	0.03	0.007	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
PTEN	-0.001	0.033	-10000	0	-0.77	2	2
HSP90AA1	0	0.009	-10000	0	-0.29	1	1
ARF6/GTP	-0.001	0.021	0.3	2	-10000	0	2
RhoA/GTP	-0.001	0.021	0.25	2	-0.36	2	4
Src family/SYK family/BLNK-LAT	-0.011	0.056	-10000	0	-0.53	6	6
BLK	-0.044	0.11	-10000	0	-0.3	159	159
PDPK1	0	0	-10000	0	-10000	0	0
CYTH1	-0.001	0.021	0.26	2	-0.36	2	4
HCK	-0.004	0.033	-10000	0	-10000	0	0
CYTH3	-0.001	0.024	0.26	2	-0.38	3	5
CYTH2	-0.001	0.021	0.26	2	-0.36	2	4
KRAS	0.011	0.013	-10000	0	-0.29	2	2
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	-0.004	0.052	-10000	0	-0.55	9	9
SGK1	-0.004	0.054	0.23	2	-0.7	6	8
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	0.034	0.033	-10000	0	-0.28	4	4
SOS1	0	0	-10000	0	-10000	0	0
SYK	0	0.009	-10000	0	-0.29	1	1
ARF6/GDP	-0.002	0.022	0.28	2	-10000	0	2
mol:PI-3-4-5-P3	-0.001	0.024	0.36	2	-0.38	2	4
ARAP3/RAP1A/GTP	-0.001	0.022	0.25	2	-0.39	2	4
VAV1	-0.003	0.043	-10000	0	-0.59	5	5
mol:PI-3-4-P2	0.022	0	-10000	0	-10000	0	0
RAS family/GTP/PI3K Class I	-0.002	0.019	-10000	0	-0.39	2	2
PLEKHA1	0.03	0.017	-10000	0	-0.52	1	1
Rac1/GDP	0.038	0.032	-10000	0	-0.3	2	2
LAT	-0.005	0.048	-10000	0	-0.35	17	17
Rac1/GTP	-0.006	0.045	-10000	0	-0.37	15	15
ITK	-0.019	0.083	0.26	1	-0.44	38	39
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.059	0.065	0.24	1	-0.39	7	8
LCK	-0.02	0.1	-10000	0	-0.41	54	54
BTK	-0.001	0.021	0.26	2	-0.36	2	4

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	-0.001	0.024	-9999	-0.79	1	1
SMAD2	0.014	0.004	-9999	-10000	0	0
SMAD3	0.042	0	-9999	-10000	0	0
SMAD3/SMAD4	0.004	0.015	-9999	-0.29	1	1
SMAD4/Ubc9/PIASy	0	0.016	-9999	-0.52	1	1
SMAD2/SMAD2/SMAD4	-0.009	0.031	-9999	-0.52	1	1
PPM1A	0	0	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
SMAD2/SMAD4	0	0.015	-9999	-0.47	1	1
MAP3K1	-0.001	0.024	-9999	-0.79	1	1
TRAP-1/SMAD4	-0.01	0.077	-9999	-0.6	18	18
MAPK3	0	0	-9999	-10000	0	0
MAPK1	0	0	-9999	-10000	0	0
NUP214	0	0	-9999	-10000	0	0
CTDSP1	0	0	-9999	-10000	0	0
CTDSP2	0	0	-9999	-10000	0	0
CTDSPL	0	0	-9999	-10000	0	0
KPNB1	0	0	-9999	-10000	0	0
TGFBRAP1	-0.012	0.098	-9999	-0.79	17	17
UBE2I	0	0	-9999	-10000	0	0
NUP153	0	0.009	-9999	-0.29	1	1
KPNA2	-0.029	0.088	-9999	-0.29	108	108
PIAS4	0	0	-9999	-10000	0	0

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.004	0.045	-9999	-0.56	6	6
PDGFB-D/PDGFRB/SLAP	-0.004	0.041	-9999	-0.6	4	4
PDGFB-D/PDGFRB/APS/CBL	-0.009	0.043	-9999	-0.51	4	4
AKT1	-0.012	0.051	-9999	-0.52	3	3
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.035	0.052	-9999	-0.59	6	6
PIK3CA	0	0.009	-9999	-0.29	1	1
FGR	-0.003	0.038	-9999	-0.53	5	5
mol:Ca2+	0.033	0.048	-9999	-0.68	4	4
MYC	0.039	0.14	-9999	-0.8	28	28
SHC1	0	0	-9999	-10000	0	0
HRAS/GDP	-0.003	0.028	-9999	-0.42	4	4
LRP1/PDGFRB/PDGFB	-0.008	0.068	-9999	-0.58	14	14
GRB10	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
GO:0007205	0.033	0.049	-9999	-0.69	4	4
PTEN	-0.001	0.034	-9999	-0.79	2	2
GRB2	0	0.009	-9999	-0.29	1	1
GRB7	-0.023	0.085	-9999	-0.31	79	79
PDGFB-D/PDGFRB/SHP2	-0.002	0.036	-9999	-0.6	4	4
PDGFB-D/PDGFRB/GRB10	-0.002	0.036	-9999	-0.6	4	4
cell cycle arrest	-0.004	0.041	-9999	-0.6	4	4
HRAS	-0.002	0.027	-9999	-0.29	9	9
HIF1A	0.05	0.06	-9999	-0.44	3	3
GAB1	0.035	0.055	-9999	-0.67	4	4
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.04	0.053	-9999	-0.61	4	4
PDGFB-D/PDGFRB	-0.003	0.035	-9999	-0.53	4	4
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	-0.002	0.036	-9999	-0.6	4	4
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.005	0.049	-9999	-0.57	6	6
positive regulation of MAPKKK cascade	-0.002	0.036	-9999	-0.6	4	4
PIK3R1	-0.009	0.086	-9999	-0.79	13	13
mol:IP3	0.033	0.049	-9999	-0.7	4	4
E5	0	0.001	-9999	-10000	0	0
CSK	0	0.002	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.017	0.067	-9999	-0.6	7	7
SHB	-0.001	0.025	-9999	-0.79	1	1
BLK	-0.002	0.049	-9999	-0.58	7	7
PTPN2	0.002	0.005	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	-0.002	0.036	-9999	-0.6	4	4
BCAR1	0	0	-9999	-10000	0	0
VAV2	0.04	0.062	-9999	-0.61	5	5
CBL	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	-0.002	0.036	-9999	-0.6	4	4
LCK	-0.01	0.08	-9999	-0.64	16	16
PDGFRB	0.009	0.049	-9999	-0.8	4	4
ACP1	0	0	-9999	-10000	0	0
HCK	-0.002	0.034	-9999	-0.51	4	4
ABL1	0.034	0.049	-9999	-0.63	4	4
PDGFB-D/PDGFRB/CBL	0.034	0.06	-9999	-0.79	4	4
PTPN1	-0.001	0.03	-9999	-0.29	11	11
SNX15	0	0	-9999	-10000	0	0
STAT3	0	0	-9999	-10000	0	0
STAT1	-0.005	0.038	-9999	-0.29	19	19
cell proliferation	0.041	0.12	-9999	-0.69	28	28
SLA	-0.003	0.029	-9999	-0.29	11	11
actin cytoskeleton reorganization	-0.002	0.028	-9999	-0.4	5	5
SRC	-0.002	0.033	-9999	-0.5	4	4
PI3K	-0.014	0.057	-9999	-0.58	3	3
PDGFB-D/PDGFRB/GRB7/SHC	-0.013	0.055	-9999	-0.52	7	7
SH2B2	-0.014	0.062	-9999	-0.29	52	52
PLCgamma1/SPHK1	0.036	0.054	-9999	-0.61	6	6
LYN	-0.002	0.033	-9999	-0.51	4	4
LRP1	-0.009	0.082	-9999	-0.79	12	12
SOS1	0	0	-9999	-10000	0	0
STAT5B	-0.002	0.041	-9999	-0.79	3	3
STAT5A	-0.006	0.067	-9999	-0.79	8	8
NCK1-2/p130 Cas	-0.002	0.026	-9999	-0.41	4	4
SPHK1	0.004	0.054	-9999	-0.33	23	23
EDG1	0.001	0.001	-9999	-10000	0	0
mol:DAG	0.033	0.049	-9999	-0.7	4	4
PLCG1	0.033	0.051	-9999	-0.72	4	4
NHERF/PDGFRB	-0.015	0.052	-9999	-0.44	6	6
YES1	-0.003	0.038	-9999	-0.52	5	5
cell migration	-0.015	0.052	-9999	-0.44	6	6
SHC/Grb2/SOS1	-0.002	0.027	-9999	-0.41	4	4
SLC9A3R2	-0.001	0.02	-9999	-0.29	5	5
SLC9A3R1	-0.026	0.083	-9999	-10000	0	0
NHERF1-2/PDGFRB/PTEN	-0.014	0.049	-9999	-0.47	6	6
FYN	-0.003	0.06	-9999	-0.89	4	4
DOK1	0.029	0.035	-9999	-0.47	4	4
HRAS/GTP	-0.002	0.018	-9999	-10000	0	0
PDGFB	0	0	-9999	-10000	0	0
RAC1	0.046	0.083	-9999	-0.44	28	28
PRKCD	0.03	0.035	-9999	-0.47	4	4
FER	0.025	0.061	-9999	-0.48	15	15
MAPKKK cascade	-0.002	0.027	-9999	-0.4	4	4
RASA1	0.03	0.035	-9999	-0.47	4	4
NCK1	0	0	-9999	-10000	0	0
NCK2	0	0	-9999	-10000	0	0
p62DOK/Csk	-0.002	0.029	-9999	-0.43	4	4
PDGFB-D/PDGFRB/SHB	-0.003	0.041	-9999	-0.6	5	5
chemotaxis	0.034	0.048	-9999	-0.61	4	4
STAT1-3-5/STAT1-3-5	-0.008	0.054	-9999	-0.46	13	13
Bovine Papilomavirus E5/PDGFRB	-0.002	0.037	-9999	-0.61	4	4
PTPRJ	0	0	-9999	-10000	0	0

×

FoxO family signaling

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
G6PC	0.029	0.038	-9999	-10000	0	0
PLK1	0.005	0.12	-9999	-0.62	8	8
CDKN1B	0.08	0.072	-9999	-0.54	3	3
FOXO3	0.039	0.11	-9999	-0.55	13	13
KAT2B	0.008	0.028	-9999	-0.83	1	1
FOXO1/SIRT1	0.007	0.038	-9999	-0.32	11	11
CAT	0.041	0.13	-9999	-0.99	8	8
CTNNB1	0	0	-9999	-10000	0	0
AKT1	0.015	0.011	-9999	-10000	0	0
FOXO1	0.032	0.04	-9999	-0.36	11	11
MAPK10	-0.038	0.18	-9999	-0.45	170	170
mol:GTP	0.002	0.001	-9999	-10000	0	0
FOXO4	0.064	0.088	-9999	-0.41	1	1
response to oxidative stress	0.005	0.013	-9999	-10000	0	0
FOXO3A/SIRT1	-0.016	0.069	-9999	-0.51	9	9
XPO1	0.012	0.001	-9999	-10000	0	0
EP300	0.01	0.005	-9999	-10000	0	0
BCL2L11	0.028	0.02	-9999	-10000	0	0
FOXO1/SKP2	-0.003	0.032	-9999	-0.32	10	10
mol:GDP	0.005	0.013	-9999	-10000	0	0
RAN	0.013	0.001	-9999	-10000	0	0
GADD45A	0.068	0.065	-9999	-10000	0	0
YWHAQ	0	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.069	0.027	-9999	-10000	0	0
MST1	-0.003	0.092	-9999	-0.6	21	21
CSNK1D	0	0	-9999	-10000	0	0
CSNK1E	0	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.049	0.045	-9999	-10000	0	0
YWHAB	0	0	-9999	-10000	0	0
MAPK8	0.033	0.042	-9999	-0.44	8	8
MAPK9	0.036	0.007	-9999	-10000	0	0
YWHAG	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
YWHAZ	-0.001	0.015	-9999	-0.29	3	3
SIRT1	0.004	0.009	-9999	-10000	0	0
SOD2	0.09	0.078	-9999	-0.45	1	1
RBL2	0.06	0.083	-9999	-0.56	2	2
RAL/GDP	0.012	0.016	-9999	-10000	0	0
CHUK	0.009	0.013	-9999	-10000	0	0
Ran/GTP	0	0	-9999	-10000	0	0
CSNK1G2	0	0	-9999	-10000	0	0
RAL/GTP	0.031	0.01	-9999	-10000	0	0
CSNK1G1	0	0	-9999	-10000	0	0
FASLG	0.002	0.18	-9999	-1.5	15	15
SKP2	0	0	-9999	-10000	0	0
USP7	0.013	0.001	-9999	-10000	0	0
IKBKB	0.009	0.018	-9999	-0.28	2	2
CCNB1	0.031	0.12	-9999	-0.64	6	6
FOXO1-3a-4/beta catenin	-0.009	0.043	-9999	-0.41	7	7
proteasomal ubiquitin-dependent protein catabolic process	-0.003	0.032	-9999	-0.32	10	10
CSNK1A1	0	0	-9999	-10000	0	0
SGK1	0.005	0.061	-9999	-0.8	6	6
CSNK1G3	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
ZFAND5	0.068	0.078	-9999	-10000	0	0
SFN	-0.016	0.099	-9999	-0.51	35	35
CDK2	0.004	0.006	-9999	-10000	0	0
FOXO3A/14-3-3	0.045	0.048	-9999	-10000	0	0
CREBBP	0.004	0.006	-9999	-10000	0	0
FBXO32	0.041	0.13	-9999	-0.95	9	9
BCL6	0.055	0.13	-9999	-1.2	7	7
RALB	0	0	-9999	-10000	0	0
RALA	0	0	-9999	-10000	0	0
YWHAH	0	0	-9999	-10000	0	0

×

Atypical NF-kappaB 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	-0.001	0.01	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	-0.006	0.057	-9999	-0.52	13	13
NF kappa B1 p50/RelA/I kappa B alpha	-0.003	0.024	-9999	-10000	0	0
NFKBIA	0.024	0.034	-9999	-0.27	13	13
MAPK14	0	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0	0.006	-9999	-10000	0	0
ARRB2	0.017	0	-9999	-10000	0	0
REL	-0.009	0.086	-9999	-0.79	13	13
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	-0.001	0.01	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0	0.006	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-0.29	1	1
NF kappa B1 p50 dimer	0	0.008	-9999	-10000	0	0
PIK3R1	-0.009	0.086	-9999	-0.79	13	13
NFKB1	0.022	0.009	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.03	0.034	-9999	-0.26	13	13
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	-0.003	0.023	-9999	-10000	0	0
SRC	0	0.009	-9999	-0.29	1	1
PI3K	-0.007	0.066	-9999	-0.6	13	13
NF kappa B1 p50/RelA	-0.004	0.029	-9999	-0.27	13	13
IKBKB	-0.001	0.013	-9999	-0.29	2	2
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
SYK	0	0.009	-9999	-0.29	1	1
I kappa B alpha/PIK3R1	-0.009	0.054	-9999	-0.44	13	13
cell death	-0.003	0.022	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	-0.006	0.057	-9999	-0.52	13	13
LCK	-0.02	0.1	-9999	-0.41	54	54
BCL3	-0.001	0.015	-9999	-10000	0	0

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	-0.003	0.019	-9999	-10000	0	0
CLOCK	0.005	0.083	-9999	-0.78	12	12
TIMELESS/CRY2	-0.001	0.01	-9999	-10000	0	0
DEC1/BMAL1	-0.001	0.014	-9999	-10000	0	0
ATR	0	0	-9999	-10000	0	0
NR1D1	0.041	0.016	-9999	-10000	0	0
ARNTL	0.014	0.002	-9999	-10000	0	0
TIMELESS	0.041	0.019	-9999	-10000	0	0
NPAS2	0.009	0.061	-9999	-0.62	9	9
CRY2	0	0	-9999	-10000	0	0
mol:CO	-0.014	0.003	-9999	-10000	0	0
CHEK1	-0.006	0.043	-9999	-0.29	24	24
mol:HEME	0.014	0.003	-9999	-10000	0	0
PER1	-0.014	0.11	-9999	-0.79	20	20
BMAL/CLOCK/NPAS2	0.03	0.07	-9999	-0.51	18	18
BMAL1/CLOCK	0.042	0.053	-9999	-10000	0	0
S phase of mitotic cell cycle	-0.003	0.019	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	-0.003	0.019	-9999	-10000	0	0
mol:NADPH	0.014	0.003	-9999	-10000	0	0
PER1/TIMELESS	-0.01	0.061	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	-0.002	0.022	-9999	-0.29	6	6

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.046	0.045	-10000	0	-0.55	1	1
BAG4	-0.006	0.055	-10000	0	-0.44	14	14
BAD	0.032	0.017	-10000	0	-10000	0	0
NFKBIA	0	0	-10000	0	-10000	0	0
BIRC3	-0.01	0.077	-10000	0	-0.51	21	21
BAX	0.032	0.019	-10000	0	-10000	0	0
EnzymeConsortium:3.1.4.12	0.015	0.012	-10000	0	-0.1	2	2
IKBKB	0.052	0.044	-10000	0	-0.51	1	1
MAP2K2	0.044	0.024	-10000	0	-0.46	1	1
MAP2K1	0.044	0.024	-10000	0	-0.46	1	1
SMPD1	0.021	0.012	-10000	0	-10000	0	0
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.051	0.048	-10000	0	-0.45	3	3
MAP2K4	0.038	0.025	-10000	0	-0.38	2	2
protein ubiquitination	0.054	0.044	-10000	0	-0.52	1	1
EnzymeConsortium:2.7.1.37	0.049	0.026	-10000	0	-0.48	1	1
response to UV	0	0	-10000	0	-0.003	1	1
RAF1	0.039	0.024	-10000	0	-0.49	1	1
CRADD	0.011	0.002	-10000	0	-10000	0	0
mol:ceramide	0.025	0.017	-10000	0	-0.14	2	2
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-10000	0	-10000	0	0
MADD	0.011	0.002	-10000	0	-10000	0	0
MAP3K1	0.032	0.022	-10000	0	-0.4	1	1
TRADD	0.011	0.002	-10000	0	-10000	0	0
RELA/p50	0	0	-10000	0	-10000	0	0
MAPK3	0.047	0.023	-10000	0	-0.45	1	1
MAPK1	0.047	0.023	-10000	0	-0.45	1	1
p50/RELA/I-kappa-B-alpha	0	0	-10000	0	-10000	0	0
FADD	0.044	0.049	-10000	0	-0.47	3	3
KSR1	0.032	0.025	-10000	0	-0.52	1	1
MAPK8	0.041	0.046	-10000	0	-0.42	9	9
TRAF2	-0.001	0.018	-10000	0	-0.29	4	4
response to radiation	0	0	-10000	0	-0.002	1	1
CHUK	0.052	0.043	-10000	0	-0.51	1	1
TNF R/SODD	-0.004	0.04	-10000	0	-0.6	4	4
TNF	-0.005	0.097	-10000	0	-0.46	38	38
CYCS	0.037	0.026	0.15	32	-10000	0	32
IKBKG	0.052	0.043	-10000	0	-0.51	1	1
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.039	0.047	-10000	0	-0.58	1	1
RELA	0	0	-10000	0	-10000	0	0
RIPK1	0	0.001	-10000	0	-10000	0	0
AIFM1	0.037	0.026	0.15	32	-10000	0	32
TNF/TNF R/SODD	-0.013	0.069	-10000	0	-0.53	17	17
TNFRSF1A	0	0.001	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-0.002	1	1
CASP8	0.028	0.012	-10000	0	-10000	0	0
NSMAF	0.046	0.045	-10000	0	-0.54	1	1
response to hydrogen peroxide	0	0	-10000	0	-0.003	1	1
BCL2	-0.027	0.14	-10000	0	-0.79	37	37

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.004	0.053	-9999	-0.48	13	13
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.005	0.044	-9999	-0.4	13	13
SUMO1	0	0	-9999	-10000	0	0
ZFPM1	-0.002	0.025	-9999	-0.29	8	8
NPC/RanGAP1/SUMO1/Ubc9	0	0.001	-9999	-10000	0	0
FKBP3	0	0	-9999	-10000	0	0
Histones	-0.003	0.022	-9999	-10000	0	0
YY1/LSF	-0.001	0.018	-9999	-0.4	2	2
SMG5	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	-0.005	0.039	-9999	-0.36	13	13
I kappa B alpha/HDAC1	-0.004	0.026	-9999	-10000	0	0
SAP18	0	0	-9999	-10000	0	0
RELA	-0.004	0.034	-9999	-0.31	13	13
HDAC1/Smad7	0	0	-9999	-10000	0	0
RANGAP1	0	0.009	-9999	-10000	0	0
HDAC3/TR2	-0.004	0.026	-9999	-10000	0	0
NuRD/MBD3 Complex	0	0.006	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.004	0.03	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.024	0.13	-9999	-0.62	42	42
GATA1	-0.005	0.037	-9999	-0.29	18	18
Mad/Max	0	0.006	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0	0.007	-9999	-10000	0	0
RBBP7	-0.002	0.025	-9999	-0.29	8	8
NPC	0	0	-9999	-10000	0	0
RBBP4	-0.001	0.024	-9999	-0.79	1	1
MAX	0	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
NFKBIA	-0.004	0.031	-9999	-10000	0	0
KAT2B	-0.001	0.024	-9999	-0.79	1	1
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0	0.008	-9999	-10000	0	0
SIN3 complex	0	0.007	-9999	-10000	0	0
SMURF1	0	0	-9999	-10000	0	0
CHD3	0	0	-9999	-10000	0	0
SAP30	-0.001	0.018	-9999	-0.29	4	4
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	-0.001	0.024	-9999	-0.79	1	1
YY1/HDAC3	-0.003	0.024	-9999	-10000	0	0
YY1/HDAC2	0	0.009	-9999	-0.29	1	1
YY1/HDAC1	0	0.009	-9999	-0.29	1	1
NuRD/MBD2 Complex (MeCP1)	0	0.006	-9999	-10000	0	0
PPARG	-0.094	0.17	-9999	-0.38	272	272
HDAC8/hEST1B	0	0	-9999	-10000	0	0
UBE2I	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
TNFRSF1A	0	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	-0.004	0.026	-9999	-10000	0	0
MBD3L2	-0.001	0.013	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
CREBBP	0	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0	0.007	-9999	-10000	0	0
HDAC1	0	0	-9999	-10000	0	0
HDAC3	-0.004	0.031	-9999	-10000	0	0
HDAC2	0	0	-9999	-10000	0	0
YY1	0.029	0.011	-9999	-0.35	1	1
HDAC8	0	0	-9999	-10000	0	0
SMAD7	0	0	-9999	-10000	0	0
NCOR2	0	0	-9999	-10000	0	0
MXD1	0	0.009	-9999	-0.29	1	1
STAT3	0.025	0	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0	0	-9999	-10000	0	0
YY1/LSF/HDAC1	-0.001	0.016	-9999	-0.46	1	1
YY1/SAP30/HDAC1	-0.001	0.01	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.025	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.004	0.03	-9999	-10000	0	0
histone deacetylation	0.046	0.008	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	-0.003	0.023	-9999	-10000	0	0
nuclear export	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GATAD2B	0	0	-9999	-10000	0	0
GATAD2A	0	0	-9999	-10000	0	0
GATA2/HDAC3	-0.017	0.079	-9999	-0.47	28	28
GATA1/HDAC1	-0.003	0.024	-9999	-10000	0	0
GATA1/HDAC3	-0.006	0.031	-9999	-10000	0	0
CHD4	0	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.011	0.071	-9999	-0.6	13	13
SIN3/HDAC complex/Mad/Max	0	0.006	-9999	-10000	0	0
NuRD Complex	0	0.007	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.003	0.022	-9999	-10000	0	0
SIN3B	0	0	-9999	-10000	0	0
MTA2	0	0	-9999	-10000	0	0
SIN3A	0	0	-9999	-10000	0	0
XPO1	0	0	-9999	-10000	0	0
SUMO1/HDAC1	0	0.001	-9999	-10000	0	0
HDAC complex	-0.001	0.017	-9999	-0.47	1	1
GATA1/Fog1	-0.004	0.029	-9999	-10000	0	0
FKBP25/HDAC1/HDAC2	0	0	-9999	-10000	0	0
TNF	-0.016	0.096	-9999	-0.46	38	38
negative regulation of cell growth	0.046	0.009	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0	0.006	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.006	0.046	-9999	-0.42	13	13
SIN3/HDAC complex/NCoR1	0	0.01	-9999	-10000	0	0
TFCP2	-0.001	0.024	-9999	-0.79	1	1
NR2C1	0	0	-9999	-10000	0	0
MBD3	0	0.009	-9999	-0.29	1	1
MBD2	0	0	-9999	-10000	0	0

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.077	0.036	-9999	-10000	0	0
ERC1	0	0	-9999	-10000	0	0
RIP2/NOD2	-0.007	0.04	-9999	-0.48	2	2
NFKBIA	0.047	0	-9999	-10000	0	0
BIRC2	0	0	-9999	-10000	0	0
IKBKB	-0.001	0.013	-9999	-0.29	2	2
RIPK2	-0.001	0.02	-9999	-0.29	5	5
IKBKG	0	0.008	-9999	-10000	0	0
IKK complex/A20	-0.003	0.043	-9999	-10000	0	0
NEMO/A20/RIP2	-0.001	0.02	-9999	-0.29	5	5
XPO1	0	0	-9999	-10000	0	0
NEMO/ATM	0	0.007	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
Exportin 1/RanGTP	0	0	-9999	-10000	0	0
IKK complex/ELKS	0	0.007	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0	0	-9999	-10000	0	0
NOD2	-0.01	0.056	-9999	-0.31	35	35
NFKB1	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
MALT1	0	0	-9999	-10000	0	0
cIAP1/UbcH5C	0	0	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
TNF/TNFR1A	-0.011	0.071	-9999	-0.6	13	13
TRAF6	0	0	-9999	-10000	0	0
PRKCA	-0.021	0.12	-9999	-0.76	30	30
CHUK	0	0	-9999	-10000	0	0
UBE2D3	0	0	-9999	-10000	0	0
TNF	-0.016	0.096	-9999	-0.46	38	38
NF kappa B1 p50/RelA	0	0	-9999	-10000	0	0
BCL10	0	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.047	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
TNFRSF1A	0	0	-9999	-10000	0	0
IKK complex	0	0.008	-9999	-10000	0	0
CYLD	0	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.009	0.059	-9999	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0	0	-9999	-10000	0	0
ITGB7	-0.01	0.058	-9999	-0.79	2	2
ITGA4	-0.003	0.028	-9999	-0.29	10	10
alpha4/beta7 Integrin	-0.008	0.046	-9999	-0.45	6	6
alpha4/beta1 Integrin	-0.002	0.018	-9999	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.028	0.047	-10000	0	-10000	0	0
regulation of axonogenesis	-0.023	0.034	0.31	10	-10000	0	10
myoblast fusion	0.008	0.026	-10000	0	-10000	0	0
mol:GTP	-0.005	0.016	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.009	0.031	-10000	0	-10000	0	0
ARF1/GTP	-0.003	0.008	-10000	0	-10000	0	0
mol:GM1	0.006	0.015	-10000	0	-10000	0	0
mol:Choline	0.02	0.053	-10000	0	-0.51	10	10
lamellipodium assembly	-0.004	0.032	-10000	0	-10000	0	0
MAPK3	0.02	0.025	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.009	0.031	-10000	0	-10000	0	0
ARF1	0	0	-10000	0	-10000	0	0
ARF6/GDP	-0.008	0.027	-10000	0	-10000	0	0
ARF1/GDP	-0.004	0.025	-10000	0	-10000	0	0
ARF6	0.007	0.008	-10000	0	-10000	0	0
RAB11A	-0.001	0.013	-10000	0	-0.29	2	2
TIAM1	0.011	0.019	-10000	0	-0.29	4	4
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.02	0.025	-10000	0	-10000	0	0
actin filament bundle formation	0.006	0.021	-10000	0	-10000	0	0
KALRN	-0.011	0.067	-10000	0	-0.47	21	21
RAB11FIP3/RAB11A	0	0.008	-10000	0	-10000	0	0
RhoA/GDP	-0.006	0.022	-10000	0	-10000	0	0
NME1	-0.003	0.066	-10000	0	-0.29	55	55
Rac1/GDP	-0.006	0.022	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	-0.005	0.016	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	-0.005	0.032	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
liver development	-0.005	0.016	-10000	0	-10000	0	0
ARF6/GTP	-0.005	0.016	-10000	0	-10000	0	0
RhoA/GTP	-0.003	0.008	-10000	0	-10000	0	0
mol:GDP	-0.006	0.03	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	-0.001	0.007	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
PLD1	0.011	0.058	-10000	0	-0.58	10	10
RAB11FIP3	0	0	-10000	0	-10000	0	0
tube morphogenesis	-0.004	0.032	-10000	0	-10000	0	0
ruffle organization	0.023	0.034	-10000	0	-0.31	10	10
regulation of epithelial cell migration	-0.005	0.016	-10000	0	-10000	0	0
PLD2	0.016	0.014	-10000	0	-10000	0	0
PIP5K1A	-0.004	0.03	-10000	0	-0.31	10	10
mol:Phosphatidic acid	0.02	0.053	-10000	0	-0.51	10	10
Rac1/GTP	-0.005	0.032	-10000	0	-10000	0	0

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.13	0.12	-9999	-0.5	10	10
CaM/Ca2+	0	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
AKT2	0	0	-9999	-10000	0	0
STXBP4	-0.001	0.013	-9999	-0.29	2	2
mol:GTP	0	0	-9999	-10000	0	0
mol:glucose	-0.12	0.15	-9999	-0.34	13	13
YWHAZ	-0.001	0.015	-9999	-0.29	3	3
CALM1	0	0	-9999	-10000	0	0
YWHAQ	0	0	-9999	-10000	0	0
TBC1D4	0.019	0.046	-9999	-0.6	6	6
mol:Ca2+	0	0	-9999	-10000	0	0
YWHAH	0	0	-9999	-10000	0	0
YWHAB	0	0	-9999	-10000	0	0
SNARE/Synip	0	0.006	-9999	-10000	0	0
YWHAG	0	0	-9999	-10000	0	0
ASIP	-0.003	0.031	-9999	-0.29	12	12
PRKCI	0	0.009	-9999	-10000	0	0
AS160/CaM/Ca2+	0	0	-9999	-10000	0	0
RHOQ	0	0	-9999	-10000	0	0
GYS1	0.032	0	-9999	-10000	0	0
PRKCZ	-0.001	0.024	-9999	-0.79	1	1
TRIP10	0	0	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
AS160/14-3-3	-0.004	0.031	-9999	-10000	0	0
VAMP2	0	0	-9999	-10000	0	0
SLC2A4	-0.13	0.16	-9999	-0.38	13	13
STX4	0	0	-9999	-10000	0	0
GSK3B	0.025	0	-9999	-10000	0	0
SFN	-0.016	0.099	-9999	-0.51	35	35
LNPEP	-0.007	0.071	-9999	-0.79	9	9
YWHAE	0	0	-9999	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0	0	-9999	-10000	0	0
Rac1/GDP	0	0.003	-9999	-10000	0	0
DOCK1	0	0	-9999	-10000	0	0
ITGA4	-0.003	0.028	-9999	-0.29	10	10
RAC1	0	0	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.008	0.046	-9999	-0.45	6	6
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.001	0.014	-9999	-10000	0	0
alpha4/beta7 Integrin/Paxillin	-0.005	0.032	-9999	-0.47	2	2
lamellipodium assembly	-0.005	0.05	-9999	-0.46	13	13
PIK3CA	0	0.009	-9999	-0.29	1	1
PI3K	-0.007	0.066	-9999	-0.6	13	13
ARF6	0	0	-9999	-10000	0	0
TLN1	0	0	-9999	-10000	0	0
PXN	0.022	0	-9999	-10000	0	0
PIK3R1	-0.009	0.086	-9999	-0.79	13	13
ARF6/GTP	-0.001	0.01	-9999	-10000	0	0
cell adhesion	-0.001	0.01	-9999	-10000	0	0
CRKL/CBL	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	-0.001	0.011	-9999	-10000	0	0
ITGB1	0	0	-9999	-10000	0	0
ITGB7	-0.01	0.058	-9999	-0.79	2	2
ARF6/GDP	0	0.003	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.007	0.049	-9999	-0.44	13	13
p130Cas/Crk/Dock1	0	0	-9999	-10000	0	0
VCAM1	-0.011	0.088	-9999	-0.63	19	19
alpha4/beta1 Integrin/Paxillin/Talin	-0.001	0.01	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.001	0.012	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
mol:GDP	0.001	0.012	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GIT1	-0.001	0.02	-9999	-0.29	5	5
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.001	0.01	-9999	-10000	0	0
Rac1/GTP	-0.005	0.056	-9999	-0.51	13	13

×

TCGA08_p53

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
CDKN2A	-0.026	0.08	-9999	-9999
TP53	-0.008	0.02	-9999	-9999
Senescence	-0.008	0.02	-9999	-9999
Apoptosis	-0.008	0.02	-9999	-9999
Activated_Oncogenes	0	0	-9999	-9999
MDM2	0.017	0.041	-9999	-9999
MDM4	0	0	-9999	-9999

×

Sumoylation by RanBP2 regulates transcriptional repression

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
HDAC1	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0.011	-9999	-0.36	1	1
MDM2/SUMO1	-0.001	0.007	-9999	-10000	0	0
HDAC4	-0.001	0.024	-9999	-0.79	1	1
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
SUMO1	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0	0.002	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.029	0.001	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0	0	-9999	-10000	0	0
SUMO1/HDAC4	0	0.013	-9999	-0.43	1	1
SUMO1/HDAC1	0	0.001	-9999	-10000	0	0
RANGAP1	0	0.009	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	-0.001	0.008	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0	0.001	-9999	-10000	0	0
Ran/GTP	0	0.001	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	-0.001	0.02	-9999	-0.29	5	5
UBE2I	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
PIAS2	0	0	-9999	-10000	0	0
PIAS1	0	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-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	-0.001	0.009	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.02	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	-0.001	0.02	-9999	-0.29	5	5
coatomer protein complex/ARF1/GTP/ER cargo protein	0	0.003	-9999	-10000	0	0
CD4	0	0	-9999	-10000	0	0
CLTA	0	0	-9999	-10000	0	0
mol:GTP	0.002	0	-9999	-10000	0	0
ARFGAP1	0.01	0.017	-9999	-0.2	7	7
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	-0.001	0.008	-9999	-10000	0	0
mol:Choline	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0	0	-9999	-10000	0	0
DDEF1	0	0	-9999	-10000	0	0
ARF1/GDP	-0.001	0.009	-9999	-10000	0	0
AP2M1	0	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	-0.001	0.01	-9999	-10000	0	0
ARFIP2	0	0	-9999	-10000	0	0
COPA	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.025	0.003	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0	-9999	-10000	0	0
GGA3	0	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0	0	-9999	-10000	0	0
AP2A1	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0	0.004	-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	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	0.001	-9999	-10000	0	0
PLD2	0	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.01	0.017	-9999	-0.2	7	7
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	0.01	0.017	-9999	-0.2	7	7
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	0	-9999	-10000	0	0

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0	0	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
CHUK	0	0	-9999	-10000	0	0
NF kappa B2 p100/RelB	-0.001	0.01	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
MAP3K14	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelB	-0.002	0.018	-9999	-10000	0	0
RELB	-0.003	0.028	-9999	-0.29	10	10
NFKB2	0	0.009	-9999	-0.29	1	1
NF kappa B2 p52/RelB	-0.002	0.015	-9999	-10000	0	0
regulation of B cell activation	-0.002	0.015	-9999	-10000	0	0

pid_entity	TCGA.Z7.A8R6	TCGA.Z7.A8R5	TCGA.XX.A89A	TCGA.XX.A899
109_MAP3K5	-0.27	0.054	0.054	0.054
47_PPARGC1A	-0.79	0	0	0
105_BMP4	0	0	0	0
105_BMP6	0	0	0	0
105_BMP7	0	0	0	0
105_BMP2	-0.79	0	0	0
131_RELN/VLDLR	-0.47	-0.47	0	0
30_TGFB1/TGF beta receptor Type II	0.013	0	0.013	0.012
84_STAT5B	-0.1	-0.073	0.032	0.046
84_STAT5A	-0.1	-0.073	0.032	0.046