PARADIGM pathway analysis of mRNASeq expression and copy number data

Pathway.Name	Avg.Num.Perturbations
Ephrin A reverse signaling	136
FOXM1 transcription factor network	123
Aurora B signaling	121
Glypican 2 network	113
Effects of Botulinum toxin	112
Retinoic acid receptors-mediated signaling	105
Reelin signaling pathway	94
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	85
Signaling mediated by p38-alpha and p38-beta	81
Ephrin B reverse signaling	79

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
Ephrin A reverse signaling	0.2033	136	954	7	-0.058	0.018	1000	-1000	-0.013	-1000
FOXM1 transcription factor network	0.1839	123	6278	51	0.02	0.3	1000	-1000	-0.15	-1000
Aurora B signaling	0.1809	121	8117	67	-0.049	0.16	1000	-1000	-0.032	-1000
Glypican 2 network	0.1689	113	455	4	0.047	0.057	1000	-1000	0.021	-1000
Effects of Botulinum toxin	0.1674	112	2937	26	-0.096	0.041	1000	-1000	-0.005	-1000
Retinoic acid receptors-mediated signaling	0.1570	105	6114	58	-0.25	0.041	1000	-1000	-0.033	-1000
Reelin signaling pathway	0.1405	94	5271	56	-0.11	0.053	1000	-1000	-0.021	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.1271	85	7265	85	-0.17	0.041	1000	-1000	-0.036	-1000
Signaling mediated by p38-alpha and p38-beta	0.1211	81	3571	44	-0.096	0.021	1000	-1000	-0.021	-1000
Ephrin B reverse signaling	0.1181	79	3821	48	-0.044	0.044	1000	-1000	-0.027	-1000
Visual signal transduction: Rods	0.1181	79	4158	52	-0.11	0.063	1000	-1000	-0.015	-1000
Aurora C signaling	0.1166	78	551	7	0	0.1	1000	-1000	-0.014	-1000
Glucocorticoid receptor regulatory network	0.1151	77	8784	114	-0.45	0.24	1000	-1000	-0.043	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.1106	74	5086	68	-0.21	0.1	1000	-1000	-0.086	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.1091	73	2485	34	-0.034	0.027	1000	-1000	-0.024	-1000
IL23-mediated signaling events	0.1076	72	4328	60	-0.42	0.056	1000	-1000	-0.13	-1000
PLK1 signaling events	0.1061	71	6090	85	-0.02	0.098	1000	-1000	-0.033	-1000
TCGA08_retinoblastoma	0.1061	71	569	8	-0.01	0.044	1000	-1000	-0.002	-1000
Thromboxane A2 receptor signaling	0.0927	62	6523	105	-0.2	0.053	1000	-1000	-0.042	-1000
a4b1 and a4b7 Integrin signaling	0.0792	53	269	5	0.021	0.042	1000	-1000	0.02	-1000
Arf6 signaling events	0.0792	53	3320	62	-0.083	0.079	1000	-1000	-0.033	-1000
HIF-1-alpha transcription factor network	0.0703	47	3614	76	-0.004	0.23	1000	-1000	-0.064	-1000
Syndecan-1-mediated signaling events	0.0688	46	1584	34	-0.042	0.057	1000	-1000	-0.024	-1000
FAS signaling pathway (CD95)	0.0673	45	2146	47	-0.18	0.046	1000	-1000	-0.044	-1000
LPA receptor mediated events	0.0673	45	4625	102	-0.045	0.052	1000	-1000	-0.06	-1000
S1P1 pathway	0.0643	43	1548	36	-0.1	0.027	1000	-1000	-0.035	-1000
Ceramide signaling pathway	0.0628	42	3217	76	-0.078	0.035	1000	-1000	-0.03	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0613	41	2265	54	-0.074	0.03	1000	-1000	-0.028	-1000
Signaling events mediated by the Hedgehog family	0.0613	41	2133	52	-0.023	0.037	1000	-1000	-0.035	-1000
p75(NTR)-mediated signaling	0.0613	41	5241	125	-0.08	0.057	1000	-1000	-0.036	-1000
amb2 Integrin signaling	0.0613	41	3370	82	-0.088	0.05	1000	-1000	-0.023	-1000
Ras signaling in the CD4+ TCR pathway	0.0583	39	673	17	-0.074	0.036	1000	-1000	-0.028	-1000
EPO signaling pathway	0.0568	38	2142	55	-0.004	0.058	1000	-1000	-0.017	-1000
Syndecan-3-mediated signaling events	0.0568	38	1337	35	-0.035	0.053	1000	-1000	-0.016	-1000
Syndecan-4-mediated signaling events	0.0568	38	2573	67	-0.03	0.083	1000	-1000	-0.038	-1000
TCGA08_p53	0.0553	37	259	7	-0.007	0.02	1000	-1000	-0.006	-1000
TCGA08_rtk_signaling	0.0538	36	951	26	-0.013	0.055	1000	-1000	0.002	-1000
EGFR-dependent Endothelin signaling events	0.0508	34	734	21	-0.009	0.066	1000	-1000	-0.022	-1000
ErbB2/ErbB3 signaling events	0.0493	33	2162	65	-0.042	0.03	1000	-1000	-0.058	-1000
Coregulation of Androgen receptor activity	0.0493	33	2550	76	-0.023	0.07	1000	-1000	-0.016	-1000
IL1-mediated signaling events	0.0493	33	2071	62	-0.019	0.064	1000	-1000	-0.03	-1000
PDGFR-alpha signaling pathway	0.0463	31	1379	44	-0.017	0.055	1000	-1000	-0.023	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0463	31	2640	83	-0.16	0.15	1000	-1000	-0.026	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0463	31	3830	120	-0.085	0.068	1000	-1000	-0.037	-1000
Osteopontin-mediated events	0.0448	30	1166	38	-0.007	0.073	1000	-1000	-0.025	-1000
JNK signaling in the CD4+ TCR pathway	0.0448	30	520	17	-0.18	0.048	1000	-1000	-0.03	-1000
BARD1 signaling events	0.0433	29	1691	57	-0.066	0.084	1000	-1000	-0.036	-1000
IL4-mediated signaling events	0.0419	28	2633	91	-0.58	0.18	1000	-1000	-0.16	-1000
BMP receptor signaling	0.0419	28	2297	81	-0.051	0.089	1000	-1000	-0.02	-1000
Glypican 1 network	0.0419	28	1350	48	-0.03	0.046	1000	-1000	-0.022	-1000
IL12-mediated signaling events	0.0404	27	2404	87	-0.11	0.077	1000	-1000	-0.086	-1000
Cellular roles of Anthrax toxin	0.0404	27	1073	39	-0.026	0.041	1000	-1000	-0.019	-1000
TCR signaling in naïve CD8+ T cells	0.0404	27	2583	93	-0.19	0.21	1000	-1000	-0.032	-1000
IL2 signaling events mediated by STAT5	0.0404	27	598	22	-0.009	0.056	1000	-1000	-0.035	-1000
Nongenotropic Androgen signaling	0.0389	26	1382	52	-0.011	0.072	1000	-1000	-0.021	-1000
IL6-mediated signaling events	0.0389	26	1969	75	-0.089	0.071	1000	-1000	-0.046	-1000
Visual signal transduction: Cones	0.0374	25	955	38	-0.011	0.056	1000	-1000	-0.012	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0374	25	1336	52	-0.05	0.05	1000	-1000	-0.035	-1000
Regulation of nuclear SMAD2/3 signaling	0.0359	24	3353	136	-0.062	0.093	1000	-1000	-0.036	-1000
Signaling events regulated by Ret tyrosine kinase	0.0359	24	2027	82	-0.02	0.054	1000	-1000	-0.032	-1000
IL2 signaling events mediated by PI3K	0.0344	23	1348	58	-0.062	0.059	1000	-1000	-0.04	-1000
Canonical Wnt signaling pathway	0.0344	23	1203	51	-0.026	0.074	1000	-1000	-0.042	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0344	23	1759	74	-0.076	0.053	1000	-1000	-0.043	-1000
Rapid glucocorticoid signaling	0.0344	23	471	20	-0.016	0.024	1000	-1000	-0.004	-1000
Aurora A signaling	0.0329	22	1354	60	-0.012	0.078	1000	-1000	-0.015	-1000
Fc-epsilon receptor I signaling in mast cells	0.0329	22	2166	97	-0.013	0.098	1000	-1000	-0.047	-1000
Insulin-mediated glucose transport	0.0329	22	723	32	-0.063	0.055	1000	-1000	-0.024	-1000
Caspase cascade in apoptosis	0.0314	21	1622	74	-0.04	0.051	1000	-1000	-0.034	-1000
PLK2 and PLK4 events	0.0314	21	63	3	-0.009	0.026	1000	-1000	-0.009	-1000
Signaling events mediated by PTP1B	0.0314	21	1622	76	-0.076	0.064	1000	-1000	-0.031	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0299	20	756	37	-0.004	0.061	1000	-1000	-0.017	-1000
E-cadherin signaling in keratinocytes	0.0284	19	833	43	-0.007	0.053	1000	-1000	-0.019	-1000
IFN-gamma pathway	0.0269	18	1231	68	-0.21	0.058	1000	-1000	-0.041	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0269	18	614	33	-0.009	0.052	1000	-1000	-0.022	-1000
Presenilin action in Notch and Wnt signaling	0.0254	17	1076	61	-0.049	0.054	1000	-1000	-0.033	-1000
Regulation of p38-alpha and p38-beta	0.0254	17	930	54	-0.07	0.044	1000	-1000	-0.035	-1000
Syndecan-2-mediated signaling events	0.0239	16	1163	69	-0.007	0.044	1000	-1000	-0.027	-1000
S1P5 pathway	0.0239	16	272	17	-0.016	0.021	1000	-1000	-0.012	-1000
Class I PI3K signaling events	0.0239	16	1189	73	-0.016	0.039	1000	-1000	-0.026	-1000
BCR signaling pathway	0.0239	16	1625	99	-0.018	0.073	1000	-1000	-0.038	-1000
VEGFR1 specific signals	0.0239	16	928	56	-0.019	0.072	1000	-1000	-0.026	-1000
Signaling events mediated by PRL	0.0239	16	557	34	-0.026	0.051	1000	-1000	-0.024	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0239	16	1316	78	-0.003	0.052	1000	-1000	-0.041	-1000
EPHB forward signaling	0.0224	15	1295	85	-0.026	0.056	1000	-1000	-0.038	-1000
Plasma membrane estrogen receptor signaling	0.0224	15	1333	86	-0.022	0.042	1000	-1000	-0.042	-1000
p38 MAPK signaling pathway	0.0224	15	683	44	-0.016	0.058	1000	-1000	-0.025	-1000
Endothelins	0.0209	14	1401	96	-0.043	0.064	1000	-1000	-0.045	-1000
Paxillin-dependent events mediated by a4b1	0.0209	14	504	36	-0.046	0.061	1000	-1000	-0.023	-1000
Calcium signaling in the CD4+ TCR pathway	0.0209	14	442	31	-0.026	0.04	1000	-1000	-0.049	-1000
E-cadherin signaling in the nascent adherens junction	0.0209	14	1134	76	-0.024	0.055	1000	-1000	-0.038	-1000
Regulation of Telomerase	0.0209	14	1481	102	-0.013	0.076	1000	-1000	-0.049	-1000
Noncanonical Wnt signaling pathway	0.0194	13	359	26	-0.016	0.03	1000	-1000	-0.029	-1000
PDGFR-beta signaling pathway	0.0194	13	1308	97	-0.022	0.083	1000	-1000	-0.03	-1000
E-cadherin signaling events	0.0194	13	68	5	0.021	0.036	1000	-1000	0.021	-1000
Integrins in angiogenesis	0.0179	12	1050	84	-0.019	0.069	1000	-1000	-0.031	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0179	12	1534	125	-0.018	0.073	1000	-1000	-0.036	-1000
S1P4 pathway	0.0179	12	323	25	-0.016	0.033	1000	-1000	-0.013	-1000
FOXA2 and FOXA3 transcription factor networks	0.0164	11	510	46	-0.032	0.047	1000	-1000	-0.1	-1000
Class I PI3K signaling events mediated by Akt	0.0164	11	805	68	-0.017	0.039	1000	-1000	-0.029	-1000
Nectin adhesion pathway	0.0164	11	703	63	-0.011	0.055	1000	-1000	-0.048	-1000
Signaling events mediated by HDAC Class III	0.0164	11	461	40	-0.025	0.034	1000	-1000	-0.027	-1000
TRAIL signaling pathway	0.0164	11	569	48	-0.012	0.061	1000	-1000	-0.021	-1000
ceramide signaling pathway	0.0164	11	547	49	-0.008	0.03	1000	-1000	-0.032	-1000
FoxO family signaling	0.0164	11	760	64	-0.023	0.065	1000	-1000	-0.064	-1000
Wnt signaling	0.0164	11	81	7	0.013	0.028	1000	-1000	-0.004	-1000
Canonical NF-kappaB pathway	0.0149	10	423	39	-0.012	0.047	1000	-1000	-0.019	-1000
Arf6 trafficking events	0.0149	10	762	71	-0.038	0.039	1000	-1000	-0.027	-1000
Insulin Pathway	0.0149	10	803	74	-0.061	0.059	1000	-1000	-0.033	-1000
Regulation of Androgen receptor activity	0.0149	10	741	70	-0.048	0.042	1000	-1000	-0.039	-1000
ErbB4 signaling events	0.0135	9	631	69	-0.032	0.053	1000	-1000	-0.027	-1000
Arf6 downstream pathway	0.0135	9	413	43	-0.034	0.039	1000	-1000	-0.022	-1000
IL27-mediated signaling events	0.0135	9	479	51	-0.15	0.034	1000	-1000	-0.044	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0135	9	826	88	-0.017	0.068	1000	-1000	-0.065	-1000
mTOR signaling pathway	0.0120	8	458	53	-0.013	0.047	1000	-1000	-0.031	-1000
Atypical NF-kappaB pathway	0.0120	8	263	31	-0.012	0.039	1000	-1000	-0.011	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0120	8	380	45	-0.017	0.058	1000	-1000	-0.04	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0105	7	200	28	-0.01	0.04	1000	-1000	-0.014	-1000
Hedgehog signaling events mediated by Gli proteins	0.0105	7	456	65	-0.009	0.048	1000	-1000	-0.046	-1000
HIF-2-alpha transcription factor network	0.0105	7	307	43	-0.099	0.1	1000	-1000	-0.05	-1000
IGF1 pathway	0.0105	7	418	57	-0.026	0.057	1000	-1000	-0.027	-1000
S1P3 pathway	0.0105	7	322	42	0	0.042	1000	-1000	-0.037	-1000
Signaling events mediated by HDAC Class I	0.0075	5	527	104	-0.04	0.048	1000	-1000	-0.03	-1000
LPA4-mediated signaling events	0.0060	4	57	12	-0.01	0	1000	-1000	-0.01	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0045	3	88	23	-0.007	0.04	1000	-1000	-0.017	-1000
Signaling events mediated by HDAC Class II	0.0045	3	226	75	-0.024	0.056	1000	-1000	-0.016	-1000
Arf1 pathway	0.0045	3	213	54	-0.015	0.036	1000	-1000	-0.011	-1000
Circadian rhythm pathway	0.0030	2	64	22	-0.007	0.044	1000	-1000	-0.035	-1000
Signaling mediated by p38-gamma and p38-delta	0.0030	2	36	15	-0.014	0.021	1000	-1000	-0.012	-1000
Class IB PI3K non-lipid kinase events	0.0015	1	3	3	-0.021	0.021	1000	-1000	-0.021	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	6	27	-0.014	0.05	1000	-1000	-0.019	-1000
Alternative NF-kappaB pathway	0.0000	0	0	13	0	0.05	1000	-1000	0	-1000
Total	NA	4005	218601	7203	-7	8	131000	-131000	-4.2	-131000

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.039	0.092	-9999	-0.15	240	240
EFNA5	0.018	0.007	-9999	-10000	0	0
FYN	-0.058	0.067	-9999	-0.14	234	234
neuron projection morphogenesis	-0.039	0.092	-9999	-0.15	240	240
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.038	0.092	-9999	-0.15	240	240
EPHA5	0.014	0.01	-9999	-10000	0	0

×

FOXM1 transcription factor network

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
NFATC3	0.27	0.21	0.6	114	-10000	0	114
PLK1	0.1	0.1	-10000	0	-0.55	1	1
BIRC5	0.13	0.1	-10000	0	-0.88	1	1
HSPA1B	0.27	0.21	0.6	116	-10000	0	116
MAP2K1	0.068	0.045	0.12	203	-10000	0	203
BRCA2	0.28	0.22	0.62	122	-10000	0	122
FOXM1	0.3	0.23	0.65	121	-10000	0	121
XRCC1	0.28	0.22	0.63	116	-10000	0	116
FOXM1B/p19	0.11	0.17	0.56	33	-10000	0	33
Cyclin D1/CDK4	0.23	0.2	0.55	102	-10000	0	102
CDC2	0.29	0.22	0.6	140	-10000	0	140
TGFA	0.25	0.2	0.54	142	-10000	0	142
SKP2	0.27	0.21	0.59	129	-10000	0	129
CCNE1	0.029	0.015	0.067	2	-10000	0	2
CKS1B	0.27	0.21	0.57	144	-10000	0	144
RB1	0.14	0.16	0.41	121	-0.53	1	122
FOXM1C/SP1	0.28	0.2	0.59	106	-10000	0	106
AURKB	0.14	0.11	-10000	0	-0.71	3	3
CENPF	0.28	0.22	0.63	115	-10000	0	115
CDK4	0.04	0.037	0.13	69	-10000	0	69
MYC	0.25	0.2	0.54	144	-10000	0	144
CHEK2	0.084	0.074	0.18	205	-10000	0	205
ONECUT1	0.26	0.2	0.56	138	-10000	0	138
CDKN2A	0.024	0.053	0.1	180	-0.03	125	305
LAMA4	0.27	0.21	0.6	119	-10000	0	119
FOXM1B/HNF6	0.27	0.21	0.6	110	-10000	0	110
FOS	0.26	0.24	0.6	121	-0.92	6	127
SP1	0.025	0.007	-10000	0	-10000	0	0
CDC25B	0.28	0.22	0.63	124	-10000	0	124
response to radiation	0.042	0.034	0.069	321	-10000	0	321
CENPB	0.28	0.22	0.62	125	-10000	0	125
CENPA	0.29	0.22	0.61	135	-10000	0	135
NEK2	0.27	0.25	0.63	119	-0.99	8	127
HIST1H2BA	0.27	0.21	0.6	115	-10000	0	115
CCNA2	0.066	0.058	0.15	223	-10000	0	223
EP300	0.02	0.004	-10000	0	-10000	0	0
CCNB1/CDK1	0.28	0.21	0.64	104	-10000	0	104
CCNB2	0.3	0.22	0.6	147	-10000	0	147
CCNB1	0.29	0.22	0.62	126	-10000	0	126
ETV5	0.27	0.21	0.61	114	-10000	0	114
ESR1	0.27	0.21	0.6	118	-0.83	1	119
CCND1	0.26	0.21	0.56	142	-10000	0	142
GSK3A	0.055	0.039	0.11	144	-10000	0	144
Cyclin A-E1/CDK1-2	0.11	0.097	0.24	208	-10000	0	208
CDK2	0.061	0.057	0.15	198	-10000	0	198
G2/M transition of mitotic cell cycle	0.049	0.042	0.083	313	-10000	0	313
FOXM1B/Cbp/p300	0.25	0.19	0.56	96	-10000	0	96
GAS1	0.28	0.22	0.61	126	-10000	0	126
MMP2	0.28	0.22	0.62	119	-10000	0	119
RB1/FOXM1C	0.21	0.2	0.55	103	-10000	0	103
CREBBP	0.021	0.002	-10000	0	-10000	0	0

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.063	0.043	0.13	102	-0.16	1	103
STMN1	0.034	0.026	0.051	460	-10000	0	460
Aurora B/RasGAP/Survivin	0.13	0.058	0.17	365	-10000	0	365
Chromosomal passenger complex/Cul3 protein complex	0.027	0.047	0.14	3	-0.3	2	5
BIRC5	0.081	0.053	0.13	369	-10000	0	369
DES	-0.049	0.25	-10000	0	-0.49	153	153
Aurora C/Aurora B/INCENP	0.08	0.042	0.14	40	-10000	0	40
Aurora B/TACC1	0.078	0.03	0.1	79	-10000	0	79
Aurora B/PP2A	0.087	0.032	0.12	3	-10000	0	3
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	0.018	0.008	-10000	0	-10000	0	0
mitotic metaphase/anaphase transition	-0.003	0.002	-10000	0	-10000	0	0
NDC80	0.072	0.047	0.092	522	-10000	0	522
Cul3 protein complex	0.036	0.016	-10000	0	-10000	0	0
KIF2C	0.061	0.046	0.11	146	-0.18	2	148
PEBP1	0.022	0.003	-10000	0	-10000	0	0
KIF20A	0.088	0.049	0.12	439	-0.017	1	440
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.087	0.032	0.11	9	-10000	0	9
SEPT1	0.021	0.004	0.12	1	-10000	0	1
SMC2	0.021	0.003	-10000	0	-10000	0	0
SMC4	0.037	0.037	0.12	101	-10000	0	101
NSUN2/NPM1/Nucleolin	0.058	0.068	0.29	2	-0.5	6	8
PSMA3	0.02	0.004	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.002	0.002	-10000	0	-10000	0	0
H3F3B	0.039	0.018	-10000	0	-10000	0	0
AURKB	0.1	0.043	0.12	514	-10000	0	514
AURKC	0.022	0.019	0.12	20	-10000	0	20
CDCA8	0.058	0.052	0.13	233	-10000	0	233
cytokinesis	0.067	0.07	0.16	145	-0.21	1	146
Aurora B/Septin1	0.1	0.08	0.21	54	-0.24	2	56
AURKA	0.04	0.042	0.12	134	-10000	0	134
INCENP	0.023	0.004	-10000	0	-10000	0	0
KLHL13	0.022	0.008	0.12	4	-10000	0	4
BUB1	0.089	0.048	0.12	446	-10000	0	446
hSgo1/Aurora B/Survivin	0.16	0.082	0.21	438	-10000	0	438
EVI5	0.02	0.008	-10000	0	-10000	0	0
RhoA/GTP	0.1	0.067	0.18	230	-0.26	1	231
SGOL1	0.087	0.05	0.12	421	-10000	0	421
CENPA	0.074	0.052	0.14	150	-0.29	2	152
NCAPG	0.1	0.041	0.12	537	-10000	0	537
Aurora B/HC8 Proteasome	0.085	0.034	0.11	20	-10000	0	20
NCAPD2	0.02	0.006	0.12	1	-10000	0	1
Aurora B/PP1-gamma	0.087	0.032	0.11	100	-10000	0	100
RHOA	0.021	0.003	-10000	0	-10000	0	0
NCAPH	0.061	0.05	0.12	255	-10000	0	255
NPM1	0.046	0.053	-10000	0	-0.34	7	7
RASA1	0.021	0.002	-10000	0	-10000	0	0
KLHL9	0.018	0.008	-10000	0	-10000	0	0
mitotic prometaphase	0.001	0.001	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.085	0.034	0.11	20	-10000	0	20
PPP1CC	0.021	0.003	-10000	0	-10000	0	0
Centraspindlin	0.1	0.074	0.19	237	-0.3	1	238
RhoA/GDP	0.015	0.002	-10000	0	-10000	0	0
NSUN2	0.046	0.053	-10000	0	-0.36	6	6
MYLK	0.04	0.017	-10000	0	-10000	0	0
KIF23	0.067	0.052	0.13	277	-10000	0	277
VIM	0.042	0.038	0.064	450	-10000	0	450
RACGAP1	0.025	0.015	0.13	12	-10000	0	12
mitosis	0	0	-10000	0	-10000	0	0
NCL	0.046	0.055	-10000	0	-0.34	7	7
Chromosomal passenger complex	0.068	0.053	0.12	236	-0.27	2	238
Chromosomal passenger complex/EVI5	0.14	0.088	0.22	348	-10000	0	348
TACC1	0.021	0.003	-10000	0	-10000	0	0
PPP2R5D	0.021	0.002	-10000	0	-10000	0	0
CUL3	0.021	0.002	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	0.05	0.047	0.12	188	-9999	188
GPC2	0.047	0.05	0.12	193	-9999	193
GPC2/Midkine	0.057	0.051	0.18	37	-9999	37
neuron projection morphogenesis	0.057	0.051	0.18	37	-9999	37

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	-0.002	0.003	-10000	0	-10000	0	0
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	-0.03	0.086	-10000	0	-0.16	212	212
STXBP1	0.018	0.008	-10000	0	-10000	0	0
ACh/CHRNA1	-0.015	0.069	0.1	92	-0.088	253	345
RAB3GAP2/RIMS1/UNC13B	-0.014	0.08	-10000	0	-0.13	208	208
mol:Ca2+	0	0	-10000	0	-10000	0	0
UniProt:P30996	0	0	-10000	0	-10000	0	0
UniProt:Q60393	0	0	-10000	0	-10000	0	0
CST086	0	0	-10000	0	-10000	0	0
RIMS1	0.014	0.01	-10000	0	-10000	0	0
mol:ACh	-0.041	0.064	0.097	45	-0.11	255	300
RAB3GAP2	0.021	0.003	-10000	0	-10000	0	0
STX1A/SNAP25/VAMP2	-0.096	0.13	-10000	0	-0.24	271	271
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	-0.015	0.069	0.1	92	-0.087	253	345
UNC13B	0.02	0.005	-10000	0	-10000	0	0
CHRNA1	0.041	0.042	0.12	132	-10000	0	132
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	-0.072	0.11	0.099	1	-0.21	249	250
SNAP25	-0.092	0.098	-10000	0	-0.19	318	318
VAMP2	0.003	0	-10000	0	-10000	0	0
SYT1	0.007	0.01	-10000	0	-10000	0	0
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	-0.056	0.084	-10000	0	-0.15	285	285
STX1A/SNAP25 fragment 1/VAMP2	-0.096	0.13	-10000	0	-0.24	271	271

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.019	0.006	-10000	0	-10000	0	0
HDAC3	0.021	0.002	-10000	0	-10000	0	0
VDR	0.023	0.017	0.12	16	-10000	0	16
Cbp/p300/PCAF	0.041	0.01	-10000	0	-10000	0	0
EP300	0.02	0.004	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	-0.041	0.058	-10000	0	-0.25	22	22
KAT2B	0.021	0.005	0.12	1	-10000	0	1
MAPK14	0.021	0.002	-10000	0	-10000	0	0
AKT1	-0.065	0.059	-10000	0	-0.22	33	33
RAR alpha/9cRA/Cyclin H	-0.12	0.1	-10000	0	-0.3	55	55
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	-0.043	0.05	-10000	0	-0.23	18	18
CDC2	0	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.098	0.086	-10000	0	-0.15	419	419
NCOR2	0.021	0.002	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.014	0.025	0.089	16	-0.15	11	27
RXRs/RARs/NRIP1/9cRA	-0.23	0.15	-10000	0	-0.33	411	411
NCOA2	0.02	0.005	-10000	0	-10000	0	0
NCOA3	0.02	0.004	-10000	0	-10000	0	0
NCOA1	0.021	0.002	-10000	0	-10000	0	0
VDR/VDR/DNA	0.023	0.017	0.12	16	-10000	0	16
RARG	0.021	0.008	0.12	3	-10000	0	3
RAR gamma1/9cRA	0.027	0.007	0.096	2	-10000	0	2
MAPK3	0.021	0.002	-10000	0	-10000	0	0
MAPK1	0.021	0.003	-10000	0	-10000	0	0
MAPK8	0.019	0.006	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.23	0.15	-10000	0	-0.32	476	476
RARA	-0.095	0.09	-10000	0	-0.17	372	372
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.044	0.055	-10000	0	-0.23	28	28
PRKCA	0.021	0.004	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.22	0.15	-10000	0	-0.32	410	410
RXRG	-0.14	0.12	-10000	0	-0.23	414	414
RXRA	-0.092	0.083	-10000	0	-0.15	400	400
RXRB	-0.13	0.11	-10000	0	-0.21	414	414
VDR/Vit D3/DNA	0.014	0.025	0.089	16	-0.15	11	27
RBP1	0.033	0.034	0.12	80	-10000	0	80
CRBP1/9-cic-RA	0.024	0.024	0.089	80	-10000	0	80
RARB	0.021	0.002	-10000	0	-10000	0	0
PRKCG	0.005	0.009	-10000	0	-10000	0	0
MNAT1	0.02	0.004	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.25	0.16	-10000	0	-0.35	460	460
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.2	0.14	-10000	0	-0.28	419	419
proteasomal ubiquitin-dependent protein catabolic process	-0.087	0.078	-10000	0	-0.26	53	53
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.22	0.15	-10000	0	-0.32	409	409
positive regulation of DNA binding	-0.11	0.093	-10000	0	-0.28	55	55
NRIP1	-0.2	0.14	-10000	0	-0.43	48	48
RXRs/RARs	-0.22	0.15	-10000	0	-0.31	421	421
RXRs/RXRs/DNA/9cRA	-0.24	0.15	-10000	0	-0.32	477	477
PRKACA	0.02	0.004	-10000	0	-10000	0	0
CDK7	0.021	0.003	-10000	0	-10000	0	0
TFIIH	0.04	0.01	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.085	0.084	-10000	0	-0.23	48	48
CCNH	0.021	0.002	-10000	0	-10000	0	0
CREBBP	0.021	0.002	-10000	0	-10000	0	0
RAR gamma2/9cRA	0.037	0.014	-10000	0	-10000	0	0

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.012	0.047	-10000	0	-0.16	44	44
VLDLR	0.02	0.006	-10000	0	-10000	0	0
CRKL	0.021	0.005	0.12	1	-10000	0	1
LRPAP1	0.021	0.003	-10000	0	-10000	0	0
FYN	0.02	0.004	-10000	0	-10000	0	0
ITGA3	0.023	0.016	0.12	16	-10000	0	16
RELN/VLDLR/Fyn	-0.018	0.075	-10000	0	-0.13	191	191
MAPK8IP1/MKK7/MAP3K11/JNK1	0.053	0.027	-10000	0	-0.12	5	5
AKT1	-0.068	0.099	-10000	0	-0.19	228	228
MAP2K7	0.021	0.003	-10000	0	-10000	0	0
RAPGEF1	0.021	0.003	-10000	0	-10000	0	0
DAB1	0.015	0.01	-10000	0	-10000	0	0
RELN/LRP8/DAB1	-0.033	0.081	-10000	0	-0.13	245	245
LRPAP1/LRP8	0.028	0.01	-10000	0	-10000	0	0
RELN/LRP8/DAB1/Fyn	-0.028	0.081	-10000	0	-0.13	242	242
DAB1/alpha3/beta1 Integrin	-0.028	0.078	-10000	0	-0.13	205	205
long-term memory	-0.11	0.13	-10000	0	-0.22	365	365
DAB1/LIS1	-0.024	0.085	-10000	0	-0.13	212	212
DAB1/CRLK/C3G	-0.028	0.08	-10000	0	-0.13	209	209
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
DAB1/NCK2	-0.024	0.085	-10000	0	-0.13	238	238
ARHGEF2	0.021	0.003	-10000	0	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	0.01	0.011	-10000	0	-10000	0	0
CDK5R1	0.019	0.006	-10000	0	-10000	0	0
RELN	0.011	0.011	-10000	0	-10000	0	0
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
RELN/LRP8/Fyn	-0.018	0.073	-10000	0	-0.13	189	189
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.067	0.12	-10000	0	-0.18	305	305
MAPK8	0.019	0.006	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.034	0.08	-10000	0	-0.13	246	246
ITGB1	0.021	0.016	0.12	12	-10000	0	12
MAP1B	-0.058	0.069	0.15	1	-0.15	212	213
RELN/LRP8	-0.017	0.073	-10000	0	-0.13	189	189
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.075	0.11	-10000	0	-0.17	337	337
PI3K	0.03	0.006	-10000	0	-10000	0	0
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.031	0.021	0.13	20	-10000	0	20
RAP1A	-0.023	0.1	0.17	91	-0.2	40	131
PAFAH1B1	0.021	0.002	-10000	0	-10000	0	0
MAPK8IP1	0.02	0.004	-10000	0	-10000	0	0
CRLK/C3G	0.03	0.007	0.11	1	-10000	0	1
GRIN2B	0.009	0.01	-10000	0	-10000	0	0
NCK2	0.021	0.001	-10000	0	-10000	0	0
neuron differentiation	-0.062	0.11	-10000	0	-0.27	101	101
neuron adhesion	-0.023	0.1	0.2	43	-0.19	38	81
LRP8	0.019	0.007	-10000	0	-10000	0	0
GSK3B	-0.07	0.093	-10000	0	-0.19	227	227
RELN/VLDLR/DAB1/Fyn	-0.029	0.081	-10000	0	-0.13	245	245
MAP3K11	0.021	0.003	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.067	0.11	-10000	0	-0.2	240	240
CDK5	0.017	0.009	-10000	0	-10000	0	0
MAPT	0.009	0.072	0.8	5	-10000	0	5
neuron migration	-0.085	0.13	0.2	34	-0.24	232	266
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.049	0.099	-10000	0	-0.26	72	72
RELN/VLDLR	-0.01	0.072	-10000	0	-0.12	190	190

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.042	0.086	0.11	1	-0.16	233	234
CRKL	-0.045	0.14	0.22	22	-0.41	23	45
mol:PIP3	0.008	0.037	-10000	0	-0.91	1	1
AKT1	0.002	0.041	-10000	0	-0.8	1	1
PTK2B	0.021	0.003	-10000	0	-10000	0	0
RAPGEF1	-0.042	0.13	0.27	12	-0.39	23	35
RANBP10	0.021	0.002	-10000	0	-10000	0	0
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
HGF/MET/SHIP2	-0.028	0.081	-10000	0	-0.14	229	229
MAP3K5	-0.047	0.14	0.23	12	-0.38	51	63
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.019	0.08	-10000	0	-0.12	226	226
AP1	0.013	0.063	0.13	94	-0.16	6	100
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.023	0.016	0.12	16	-10000	0	16
apoptosis	-0.094	0.3	-10000	0	-0.78	100	100
STAT3 (dimer)	-0.049	0.086	-10000	0	-0.17	208	208
GAB1/CRKL/SHP2/PI3K	-0.028	0.14	0.29	3	-0.38	23	26
INPP5D	0.021	0.009	0.12	5	-10000	0	5
CBL/CRK	-0.033	0.14	0.22	16	-0.38	24	40
PTPN11	0.021	0.003	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.02	0.004	-10000	0	-10000	0	0
PTEN	0.018	0.007	-10000	0	-10000	0	0
ELK1	0.041	0.17	0.35	142	-0.25	1	143
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.035	0.063	-10000	0	-0.21	23	23
PAK1	-0.023	0.059	-10000	0	-0.85	1	1
HGF/MET/RANBP10	-0.029	0.082	-10000	0	-0.14	231	231
HRAS	-0.17	0.24	-10000	0	-0.49	236	236
DOCK1	-0.044	0.13	0.23	17	-0.39	23	40
GAB1	-0.051	0.13	-10000	0	-0.43	22	22
CRK	-0.045	0.14	0.22	19	-0.41	23	42
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.14	0.21	-10000	0	-0.43	234	234
JUN	0.019	0.007	-10000	0	-10000	0	0
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.055	0.084	-10000	0	-0.17	228	228
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
cell morphogenesis	-0.05	0.14	0.28	26	-0.36	19	45
GRB2/SHC	-0.037	0.09	0.22	2	-0.16	223	225
FOS	0.021	0.013	0.12	8	-10000	0	8
GLMN	0.002	0.001	-10000	0	-10000	0	0
cell motility	0.04	0.17	0.35	142	-0.25	1	143
HGF/MET/MUC20	-0.033	0.074	0.096	6	-0.13	232	238
cell migration	-0.036	0.089	0.21	2	-0.16	223	225
GRB2	0.02	0.004	-10000	0	-10000	0	0
CBL	0.021	0.003	-10000	0	-10000	0	0
MET/RANBP10	-0.042	0.086	0.11	1	-0.16	233	234
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.045	0.084	-10000	0	-0.16	214	214
MET/MUC20	-0.047	0.078	0.089	1	-0.15	234	235
RAP1B	-0.039	0.13	0.31	16	-0.37	23	39
RAP1A	-0.04	0.13	0.29	10	-0.36	23	33
HGF/MET/RANBP9	-0.029	0.082	-10000	0	-0.14	231	231
RAF1	-0.16	0.24	-10000	0	-0.46	239	239
STAT3	-0.049	0.086	-10000	0	-0.17	208	208
cell proliferation	-0.085	0.14	0.21	14	-0.28	217	231
RPS6KB1	-0.024	0.047	-10000	0	-0.2	5	5
MAPK3	0.03	0.16	0.4	38	-10000	0	38
MAPK1	0.038	0.18	0.39	88	-10000	0	88
RANBP9	0.021	0.003	-10000	0	-10000	0	0
MAPK8	-0.062	0.13	0.27	3	-0.39	32	35
SRC	-0.047	0.078	-10000	0	-0.16	210	210
PI3K	-0.04	0.089	-10000	0	-0.16	231	231
MET/Glomulin	-0.011	0.06	0.097	1	-0.17	70	71
SOS1	0.021	0.001	-10000	0	-10000	0	0
MAP2K1	-0.15	0.22	0.28	2	-0.43	238	240
MET	0.009	0.011	0.12	1	-10000	0	1
MAP4K1	-0.048	0.15	0.22	16	-0.4	52	68
PTK2	0.019	0.006	-10000	0	-10000	0	0
MAP2K2	-0.15	0.23	0.28	10	-0.43	238	248
BAD	0	0.043	-10000	0	-0.76	1	1
MAP2K4	-0.046	0.14	0.25	10	-0.35	51	61
SHP2/GRB2/SOS1/GAB1	-0.065	0.13	-10000	0	-0.24	207	207
INPPL1	0.021	0.003	-10000	0	-10000	0	0
PXN	0.021	0.002	-10000	0	-10000	0	0
SH3KBP1	0.021	0.001	-10000	0	-10000	0	0
HGS	-0.053	0.075	0.073	1	-0.16	217	218
PLCgamma1/PKC	0.015	0.003	-10000	0	-10000	0	0
HGF	0.018	0.013	0.12	5	-10000	0	5
RASA1	0.021	0.002	-10000	0	-10000	0	0
NCK1	0.021	0.005	0.12	1	-10000	0	1
PTPRJ	0.021	0.003	-10000	0	-10000	0	0
NCK/PLCgamma1	-0.039	0.088	-10000	0	-0.16	227	227
PDPK1	0.006	0.041	-10000	0	-0.84	1	1
HGF/MET/SHIP	-0.028	0.082	-10000	0	-0.14	232	232

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	-0.096	0.29	-10000	0	-0.79	95	95
MKNK1	0.019	0.006	-10000	0	-10000	0	0
MAPK14	-0.012	0.11	-10000	0	-0.27	96	96
ATF2/c-Jun	-0.021	0.077	-10000	0	-0.22	75	75
MAPK11	-0.014	0.11	-10000	0	-0.27	96	96
MITF	-0.027	0.12	-10000	0	-0.31	95	95
MAPKAPK5	-0.027	0.12	-10000	0	-0.31	96	96
KRT8	-0.023	0.12	-10000	0	-0.31	95	95
MAPKAPK3	0.021	0.003	-10000	0	-10000	0	0
MAPKAPK2	0.021	0.005	0.12	1	-10000	0	1
p38alpha-beta/CK2	-0.021	0.15	-10000	0	-0.38	96	96
CEBPB	-0.026	0.12	-10000	0	-0.31	93	93
SLC9A1	-0.035	0.13	-10000	0	-0.34	96	96
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	-0.021	0.12	-10000	0	-0.29	96	96
p38alpha-beta/MNK1	-0.007	0.12	-10000	0	-0.3	96	96
JUN	-0.019	0.074	-10000	0	-0.22	75	75
PPARGC1A	-0.029	0.12	-10000	0	-0.32	98	98
USF1	-0.027	0.12	-10000	0	-0.31	96	96
RAB5/GDP/GDI1	-0.016	0.092	-10000	0	-0.23	97	97
NOS2	-0.032	0.15	-10000	0	-0.36	93	93
DDIT3	-0.026	0.12	-10000	0	-0.31	92	92
RAB5A	0.021	0.002	-10000	0	-10000	0	0
HSPB1	0.01	0.14	0.27	90	-0.26	85	175
p38alpha-beta/HBP1	-0.006	0.12	-10000	0	-0.3	80	80
CREB1	-0.03	0.13	-10000	0	-0.34	94	94
RAB5/GDP	0.015	0.002	-10000	0	-10000	0	0
EIF4E	-0.048	0.092	-10000	0	-0.27	95	95
RPS6KA4	-0.027	0.12	-10000	0	-0.31	95	95
PLA2G4A	-0.047	0.092	-10000	0	-0.27	95	95
GDI1	-0.027	0.12	-10000	0	-0.31	96	96
TP53	-0.044	0.14	-10000	0	-0.38	95	95
RPS6KA5	-0.029	0.12	-10000	0	-0.32	95	95
ESR1	-0.029	0.12	-10000	0	-0.32	96	96
HBP1	0.017	0.01	0.12	1	-10000	0	1
MEF2C	-0.031	0.13	-10000	0	-0.34	93	93
MEF2A	-0.028	0.12	-10000	0	-0.32	96	96
EIF4EBP1	-0.024	0.13	-10000	0	-0.34	95	95
KRT19	-0.038	0.13	-10000	0	-0.31	116	116
ELK4	-0.027	0.12	-10000	0	-0.31	95	95
ATF6	-0.027	0.12	-10000	0	-0.31	96	96
ATF1	-0.032	0.13	-10000	0	-0.34	95	95
p38alpha-beta/MAPKAPK2	-0.003	0.13	-10000	0	-0.3	96	96
p38alpha-beta/MAPKAPK3	-0.002	0.13	-10000	0	-0.3	95	95

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.02	0.004	-10000	0	-10000	0	0
EPHB2	0.018	0.006	-10000	0	-10000	0	0
EFNB1	-0.007	0.014	0.051	1	-0.14	5	6
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.033	0.074	-10000	0	-0.11	290	290
Ephrin B2/EPHB1-2	0.033	0.02	-10000	0	-0.11	6	6
neuron projection morphogenesis	-0.037	0.065	-10000	0	-0.11	290	290
Ephrin B1/EPHB1-2/Tiam1	-0.043	0.078	-10000	0	-0.12	338	338
DNM1	0.009	0.01	-10000	0	-10000	0	0
cell-cell signaling	-0.001	0.002	-10000	0	-10000	0	0
MAP2K4	-0.007	0.042	-10000	0	-0.41	7	7
YES1	0.005	0.068	-10000	0	-0.64	7	7
Ephrin B1/EPHB1-2/NCK2	-0.044	0.078	-10000	0	-0.12	344	344
PI3K	0.027	0.047	-10000	0	-0.39	8	8
mol:GDP	-0.043	0.077	-10000	0	-0.12	338	338
ITGA2B	0.021	0.003	-10000	0	-10000	0	0
endothelial cell proliferation	0.023	0.016	0.095	12	-0.13	1	13
FYN	0.003	0.07	-10000	0	-0.63	7	7
MAP3K7	-0.005	0.044	-10000	0	-0.43	7	7
FGR	0.006	0.068	-10000	0	-0.64	7	7
TIAM1	0.02	0.004	-10000	0	-10000	0	0
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
RGS3	0.021	0.003	-10000	0	-10000	0	0
cell adhesion	0.019	0.048	-10000	0	-0.39	7	7
LYN	0.007	0.066	-10000	0	-0.62	7	7
Ephrin B1/EPHB1-2/Src Family Kinases	0.001	0.059	-10000	0	-0.56	7	7
Ephrin B1/EPHB1-2	-0.001	0.048	-10000	0	-0.47	7	7
SRC	0.006	0.065	-10000	0	-0.62	7	7
ITGB3	0.04	0.04	0.12	124	-10000	0	124
EPHB1	0.022	0.011	0.13	7	-10000	0	7
EPHB4	0.019	0.017	0.12	13	-10000	0	13
RAC1	0.018	0.008	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.023	0.017	0.096	12	-0.13	1	13
alphaIIb/beta3 Integrin	0.043	0.036	0.11	123	-0.15	7	130
BLK	0.011	0.066	-10000	0	-0.62	7	7
HCK	0.008	0.065	-10000	0	-0.62	7	7
regulation of stress fiber formation	0.044	0.077	0.12	344	-10000	0	344
MAPK8	-0.01	0.042	0.18	2	-0.39	7	9
Ephrin B1/EPHB1-2/RGS3	-0.044	0.078	-10000	0	-0.12	344	344
endothelial cell migration	0.027	0.083	0.19	121	-0.35	6	127
NCK2	0.021	0.001	-10000	0	-10000	0	0
PTPN13	0.023	0.007	0.13	1	-10000	0	1
regulation of focal adhesion formation	0.044	0.077	0.12	344	-10000	0	344
chemotaxis	0.044	0.077	0.12	344	-10000	0	344
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
Rac1/GTP	-0.035	0.069	-10000	0	-0.11	290	290
angiogenesis	-0.001	0.048	-10000	0	-0.46	7	7
LCK	0.011	0.069	-10000	0	-0.64	7	7

×

Visual signal transduction: Rods

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
mol:K +	0.021	0.003	-10000	0	-10000	0	0
GNAT1/GTP	0.015	0.004	0.089	1	-10000	0	1
Metarhodopsin II/Arrestin	-0.019	0.069	-10000	0	-0.13	186	186
PDE6G/GNAT1/GTP	0.039	0.027	0.096	87	-10000	0	87
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	0.02	0.005	0.12	1	-10000	0	1
GRK1	0.02	0.006	0.12	1	-10000	0	1
CNG Channel	-0.049	0.076	-10000	0	-0.11	369	369
mol:Na +	-0.092	0.09	-10000	0	-0.15	465	465
mol:ADP	0.02	0.006	0.12	1	-10000	0	1
RGS9-1/Gbeta5/R9AP	0.04	0.026	-10000	0	-0.12	4	4
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	-0.092	0.095	-10000	0	-0.15	465	465
CNGB1	0.007	0.009	-10000	0	-10000	0	0
RDH5	0.028	0.028	0.12	51	-10000	0	51
SAG	0.016	0.003	-10000	0	-10000	0	0
mol:Ca2+	-0.11	0.073	0.19	9	-0.2	170	179
Na + (4 Units)	-0.092	0.085	-10000	0	-0.14	435	435
RGS9	0.027	0.026	0.12	43	-10000	0	43
GNB1/GNGT1	0.019	0.012	-10000	0	-10000	0	0
GNAT1/GDP	0.045	0.026	-10000	0	-0.1	4	4
GUCY2D	0.021	0.014	0.12	11	-10000	0	11
GNGT1	0.012	0.006	-10000	0	-10000	0	0
GUCY2F	0.02	0.01	0.12	6	-10000	0	6
GNB5	0.021	0.003	-10000	0	-10000	0	0
mol:GMP (4 units)	0.016	0.032	0.095	22	-0.11	18	40
mol:11-cis-retinal	0.028	0.028	0.12	51	-10000	0	51
mol:cGMP	-0.021	0.077	-10000	0	-0.12	250	250
GNB1	0.019	0.007	-10000	0	-10000	0	0
Rhodopsin	-0.019	0.086	0.1	24	-0.16	184	208
SLC24A1	0.021	0.003	-10000	0	-10000	0	0
CNGA1	0.021	0.009	0.12	4	-10000	0	4
Metarhodopsin II	-0.014	0.062	0.091	1	-0.11	183	184
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	-0.016	0.085	-10000	0	-0.12	251	251
RGS9BP	0.019	0.006	-10000	0	-10000	0	0
Metarhodopsin II/Transducin	-0.024	0.064	-10000	0	-0.16	123	123
GCAP Family/Ca ++	-0.022	0.076	-10000	0	-0.12	251	251
PDE6A/B	0.03	0.038	-10000	0	-0.16	19	19
mol:Pi	0.04	0.026	-10000	0	-0.12	4	4
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	0.026	0.017	-10000	0	-10000	0	0
PDE6B	0.02	0.004	-10000	0	-10000	0	0
PDE6A	0.029	0.028	0.12	52	-10000	0	52
PDE6G	0.039	0.04	0.12	120	-10000	0	120
RHO	0.014	0.009	-10000	0	-10000	0	0
PDE6	0.063	0.05	0.17	22	-0.11	19	41
GUCA1A	0.012	0.01	-10000	0	-10000	0	0
GC2/GCAP Family	-0.016	0.084	-10000	0	-0.12	250	250
GUCA1C	0.017	0.005	0.12	1	-10000	0	1
GUCA1B	0.021	0.002	-10000	0	-10000	0	0

×

Aurora C signaling

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.Total.Perturbations
INCENP	0.021	0.003	-10000	0	-9999	0
Aurora C/Aurora B/INCENP	0.079	0.042	0.17	17	-9999	17
metaphase	0	0	-10000	0	-9999	0
mitosis	0	0	-10000	0	-9999	0
H3F3B	0.011	0.005	-10000	0	-9999	0
AURKB	0.1	0.043	0.12	514	-9999	514
AURKC	0.022	0.019	0.12	20	-9999	20

×

Glucocorticoid receptor regulatory network

Figure S13. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S13. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.081	0.074	0.26	2	-0.26	2	4
SMARCC2	0.021	0.004	-10000	0	-10000	0	0
SMARCC1	0.021	0.005	0.12	1	-10000	0	1
TBX21	-0.049	0.093	-10000	0	-0.25	60	60
SUMO2	0.019	0.009	-10000	0	-0.026	19	19
STAT1 (dimer)	0.027	0.016	0.15	7	-10000	0	7
FKBP4	0.02	0.005	-10000	0	-10000	0	0
FKBP5	0.026	0.023	0.12	35	-10000	0	35
GR alpha/HSP90/FKBP51/HSP90	0.11	0.081	0.22	158	-10000	0	158
PRL	-0.084	0.08	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/TIF2	0.21	0.18	0.41	217	-10000	0	217
RELA	-0.04	0.094	-10000	0	-0.16	250	250
FGG	0.19	0.16	0.37	206	-10000	0	206
GR beta/TIF2	0.11	0.09	0.22	180	-0.18	3	183
IFNG	-0.21	0.2	-10000	0	-0.44	236	236
apoptosis	0.039	0.086	0.45	2	-0.38	2	4
CREB1	0.023	0.007	-10000	0	-10000	0	0
histone acetylation	-0.1	0.097	-10000	0	-0.26	97	97
BGLAP	-0.097	0.098	-10000	0	-0.32	18	18
GR/PKAc	0.1	0.08	0.22	114	-10000	0	114
NF kappa B1 p50/RelA	-0.064	0.16	0.22	2	-0.26	242	244
SMARCD1	0.021	0.004	-10000	0	-10000	0	0
MDM2	0.085	0.073	0.17	203	-10000	0	203
GATA3	0.039	0.043	0.13	122	-10000	0	122
AKT1	0.019	0.005	-10000	0	-0.049	1	1
CSF2	-0.11	0.094	-10000	0	-0.48	1	1
GSK3B	0.019	0.009	-10000	0	-0.026	20	20
NR1I3	0.041	0.083	0.42	2	-10000	0	2
CSN2	0.16	0.14	0.31	235	-10000	0	235
BRG1/BAF155/BAF170/BAF60A	0.052	0.015	-10000	0	-10000	0	0
NFATC1	0.02	0.004	-10000	0	-10000	0	0
POU2F1	0.022	0.008	0.12	3	-10000	0	3
CDKN1A	0.021	0.042	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0	0.003	-10000	0	-10000	0	0
SFN	0.022	0.02	0.12	23	-10000	0	23
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.11	0.081	0.22	138	-10000	0	138
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	0.025	0.14	0.41	2	-0.67	20	22
JUN	-0.11	0.14	-10000	0	-0.29	208	208
IL4	-0.11	0.098	-10000	0	-0.33	20	20
CDK5R1	0.018	0.009	-10000	0	-0.019	20	20
PRKACA	0.02	0.004	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.04	0.057	-10000	0	-0.18	56	56
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.11	0.081	0.22	124	-10000	0	124
cortisol/GR alpha (monomer)	0.24	0.2	0.47	200	-10000	0	200
NCOA2	0.02	0.005	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.04	0.071	0.13	5	-0.11	279	284
AP-1/NFAT1-c-4	-0.21	0.22	-10000	0	-0.42	314	314
AFP	-0.14	0.12	-10000	0	-0.5	3	3
SUV420H1	0.021	0.003	-10000	0	-10000	0	0
IRF1	0.15	0.11	0.31	104	-10000	0	104
TP53	0.043	0.036	-10000	0	-10000	0	0
PPP5C	0.019	0.007	-10000	0	-10000	0	0
KRT17	-0.45	0.43	-10000	0	-0.9	303	303
KRT14	-0.095	0.093	-10000	0	-0.41	1	1
TBP	0.022	0.006	-10000	0	-10000	0	0
CREBBP	0.017	0.018	-10000	0	-10000	0	0
HDAC1	0.018	0.007	-10000	0	-10000	0	0
HDAC2	0.02	0.004	-10000	0	-10000	0	0
AP-1	-0.21	0.22	-10000	0	-0.42	315	315
MAPK14	0.019	0.008	-10000	0	-0.024	20	20
MAPK10	0.019	0.008	-10000	0	-0.024	19	19
MAPK11	0.019	0.009	-10000	0	-0.026	20	20
KRT5	-0.3	0.35	-10000	0	-0.74	210	210
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
NCOA1	0.022	0.002	-10000	0	-10000	0	0
STAT1	0.027	0.016	0.15	7	-10000	0	7
CGA	-0.1	0.099	-10000	0	-0.32	25	25
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.084	0.086	0.27	16	-10000	0	16
MAPK3	0.02	0.008	-10000	0	-0.024	20	20
MAPK1	0.019	0.008	-10000	0	-0.024	20	20
ICAM1	-0.16	0.18	-10000	0	-0.42	147	147
NFKB1	-0.04	0.095	-10000	0	-0.16	250	250
MAPK8	-0.11	0.12	-10000	0	-0.25	223	223
MAPK9	0.019	0.008	-10000	0	-0.024	11	11
cortisol/GR alpha (dimer)	0.038	0.087	0.46	2	-0.39	2	4
BAX	-0.001	0.064	-10000	0	-10000	0	0
POMC	-0.13	0.14	0.93	1	-1.2	4	5
EP300	0.016	0.018	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/p53	0.23	0.18	0.43	209	-10000	0	209
proteasomal ubiquitin-dependent protein catabolic process	0.065	0.077	0.2	83	-10000	0	83
SGK1	0.037	0.058	-10000	0	-10000	0	0
IL13	-0.17	0.18	-10000	0	-0.48	88	88
IL6	-0.21	0.3	-10000	0	-0.67	161	161
PRKACG	0.019	0.009	0.12	4	-10000	0	4
IL5	-0.14	0.15	-10000	0	-0.54	21	21
IL2	-0.22	0.2	-10000	0	-0.47	171	171
CDK5	0.015	0.01	-10000	0	-10000	0	0
PRKACB	0.018	0.007	-10000	0	-10000	0	0
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
IL8	-0.22	0.28	-10000	0	-0.65	157	157
CDK5R1/CDK5	0.01	0.047	-10000	0	-0.16	44	44
NF kappa B1 p50/RelA/PKAc	-0.026	0.13	0.21	2	-0.21	170	172
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.19	0.18	0.39	213	-10000	0	213
SMARCA4	0.021	0.004	-10000	0	-10000	0	0
chromatin remodeling	0.13	0.11	0.28	167	-10000	0	167
NF kappa B1 p50/RelA/Cbp	-0.036	0.14	-10000	0	-0.27	82	82
JUN (dimer)	-0.11	0.14	-10000	0	-0.29	205	205
YWHAH	0.02	0.005	-10000	0	-10000	0	0
VIPR1	-0.17	0.26	-10000	0	-0.56	203	203
NR3C1	0.14	0.13	0.29	204	-10000	0	204
NR4A1	0.021	0.032	-10000	0	-0.43	3	3
TIF2/SUV420H1	0.027	0.025	-10000	0	-0.16	11	11
MAPKKK cascade	0.039	0.086	0.45	2	-0.38	2	4
cortisol/GR alpha (dimer)/Src-1	0.22	0.18	0.42	200	-10000	0	200
PBX1	0.021	0.003	-10000	0	-10000	0	0
POU1F1	0.018	0.004	-10000	0	-10000	0	0
SELE	-0.27	0.33	-10000	0	-0.68	222	222
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.13	0.11	0.28	166	-10000	0	166
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.19	0.18	0.39	213	-10000	0	213
mol:cortisol	0.13	0.12	0.27	208	-10000	0	208
MMP1	-0.035	0.072	-10000	0	-0.44	1	1

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	0.028	0.013	0.17	2	-10000	0	2
NFATC2	0.01	0.12	0.32	4	-0.34	3	7
NFATC3	-0.045	0.11	-10000	0	-0.25	131	131
CD40LG	-0.12	0.3	0.35	1	-0.7	132	133
ITCH	-0.055	0.084	-10000	0	-0.16	249	249
CBLB	-0.054	0.085	-10000	0	-0.16	240	240
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.047	0.2	0.33	3	-0.65	26	29
JUNB	0.021	0.006	0.12	1	-10000	0	1
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.063	0.1	-10000	0	-0.19	273	273
T cell anergy	-0.11	0.14	-10000	0	-0.28	266	266
TLE4	-0.001	0.069	-10000	0	-0.25	1	1
Jun/NFAT1-c-4/p21SNFT	-0.09	0.33	-10000	0	-0.73	132	132
AP-1/NFAT1-c-4	-0.093	0.36	0.43	3	-0.77	133	136
IKZF1	0	0.068	0.26	5	-0.25	1	6
T-helper 2 cell differentiation	-0.015	0.16	-10000	0	-0.65	19	19
AP-1/NFAT1	0.025	0.092	0.26	5	-0.24	5	10
CALM1	-0.034	0.072	-10000	0	-0.12	257	257
EGR2	-0.11	0.29	-10000	0	-0.64	132	132
EGR3	-0.21	0.47	-10000	0	-1.1	133	133
NFAT1/FOXP3	0.032	0.094	0.29	7	-0.24	2	9
EGR1	0.019	0.012	0.12	2	-0.038	20	22
JUN	0.015	0.018	-10000	0	-0.053	5	5
EGR4	0.009	0.014	0.12	1	-0.039	17	18
mol:Ca2+	-0.044	0.057	-10000	0	-0.11	276	276
GBP3	0.019	0.081	0.24	10	-0.25	1	11
FOSL1	0.04	0.041	0.12	126	-10000	0	126
NFAT1-c-4/MAF/IRF4	-0.084	0.32	-10000	0	-0.71	132	132
DGKA	-0.002	0.07	-10000	0	-0.25	1	1
CREM	0.019	0.007	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.098	0.33	-10000	0	-0.73	132	132
CTLA4	0.004	0.068	0.22	7	-10000	0	7
NFAT1-c-4 (dimer)/EGR1	-0.1	0.34	0.37	1	-0.75	132	133
NFAT1-c-4 (dimer)/EGR4	-0.17	0.33	-10000	0	-0.8	133	133
FOS	0.016	0.025	0.13	8	-0.09	6	14
IFNG	-0.017	0.1	-10000	0	-0.46	5	5
T cell activation	-0.025	0.14	-10000	0	-0.48	6	6
MAF	0.021	0.002	-10000	0	-10000	0	0
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.1	0.24	0.57	134	-10000	0	134
TNF	-0.18	0.32	-10000	0	-0.77	135	135
FASLG	-0.18	0.41	-10000	0	-0.97	133	133
TBX21	0.028	0.026	0.13	41	-10000	0	41
BATF3	0.022	0.013	0.12	10	-10000	0	10
PRKCQ	0.019	0.009	0.12	1	-10000	0	1
PTPN1	-0.002	0.071	-10000	0	-0.25	1	1
NFAT1-c-4/ICER1	-0.1	0.32	-10000	0	-0.73	131	131
GATA3	0.037	0.042	0.12	122	-10000	0	122
T-helper 1 cell differentiation	-0.017	0.1	-10000	0	-0.45	5	5
IL2RA	-0.04	0.21	0.33	4	-0.57	39	43
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.001	0.07	-10000	0	-10000	0	0
E2F1	0.026	0.016	0.15	7	-10000	0	7
PPARG	0.021	0.006	0.12	2	-10000	0	2
SLC3A2	-0.002	0.07	-10000	0	-0.25	1	1
IRF4	0.023	0.016	0.12	16	-10000	0	16
PTGS2	-0.14	0.32	0.35	1	-0.74	133	134
CSF2	-0.13	0.3	0.34	1	-0.7	133	134
JunB/Fra1/NFAT1-c-4	-0.075	0.32	0.4	1	-0.7	132	133
IL4	-0.016	0.17	-10000	0	-0.68	19	19
IL5	-0.13	0.3	0.34	1	-0.69	133	134
IL2	-0.026	0.14	-10000	0	-0.48	6	6
IL3	-0.011	0.075	-10000	0	-0.66	4	4
RNF128	-0.12	0.17	-10000	0	-0.34	257	257
NFATC1	-0.1	0.24	-10000	0	-0.58	134	134
CDK4	0.071	0.16	0.52	23	-10000	0	23
PTPRK	-0.001	0.068	-10000	0	-0.23	1	1
IL8	-0.13	0.32	0.39	2	-0.72	133	135
POU2F1	0.021	0.007	0.12	3	-10000	0	3

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0.002	0.076	0.16	110	-0.14	2	112
KIRREL	0.018	0.036	0.12	42	-0.037	102	144
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.002	0.076	0.14	2	-0.16	110	112
PLCG1	0.02	0.004	-10000	0	-10000	0	0
ARRB2	0.021	0.002	-10000	0	-10000	0	0
WASL	0.017	0.008	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	0.018	0.068	0.17	1	-0.12	110	111
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.016	0.066	-10000	0	-0.18	86	86
FYN	-0.026	0.051	0.14	17	-0.12	108	125
mol:Ca2+	0.016	0.066	0.17	2	-0.12	108	110
mol:DAG	0.017	0.067	0.17	2	-0.12	108	110
NPHS2	0.006	0.022	-10000	0	-0.039	110	110
mol:IP3	0.017	0.067	0.17	2	-0.12	108	110
regulation of endocytosis	0.011	0.062	-10000	0	-0.12	110	110
Nephrin/NEPH1/podocin/Cholesterol	0.009	0.061	0.16	2	-0.12	110	112
establishment of cell polarity	-0.002	0.076	0.14	2	-0.16	110	112
Nephrin/NEPH1/podocin/NCK1-2	0.027	0.069	0.18	2	-0.12	109	111
Nephrin/NEPH1/beta Arrestin2	0.012	0.063	-10000	0	-0.12	110	110
NPHS1	0.015	0.01	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin	0.008	0.062	-10000	0	-0.12	110	110
TJP1	0.021	0.003	-10000	0	-10000	0	0
NCK1	0.021	0.005	0.12	1	-10000	0	1
NCK2	0.021	0.001	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.017	0.067	0.18	2	-0.12	108	110
CD2AP	0.021	0.002	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	0.018	0.067	0.18	2	-0.12	106	108
GRB2	0.02	0.004	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.024	0.048	0.14	18	-0.11	108	126
cytoskeleton organization	-0.034	0.076	0.2	11	-0.21	84	95
Nephrin/NEPH1	0.004	0.052	0.088	29	-0.11	110	139
Nephrin/NEPH1/ZO-1	0.011	0.066	0.13	1	-0.13	110	111

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.27	0.44	-10000	0	-1.1	103	103
IL23A	-0.29	0.46	-10000	0	-1.2	85	85
NF kappa B1 p50/RelA/I kappa B alpha	-0.26	0.44	-10000	0	-1	126	126
positive regulation of T cell mediated cytotoxicity	-0.3	0.48	-10000	0	-1.1	127	127
ITGA3	-0.27	0.42	-10000	0	-1.1	92	92
IL17F	-0.19	0.29	0.4	1	-0.66	128	129
IL12B	-0.007	0.045	0.12	11	-0.067	30	41
STAT1 (dimer)	-0.28	0.47	-10000	0	-1.1	127	127
CD4	-0.26	0.42	-10000	0	-1	101	101
IL23	-0.28	0.45	-10000	0	-1.2	84	84
IL23R	-0.12	0.31	-10000	0	-0.97	67	67
IL1B	-0.31	0.5	-10000	0	-1.3	101	101
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.26	0.42	-10000	0	-1.1	92	92
TYK2	-0.006	0.036	-10000	0	-10000	0	0
STAT4	0.009	0.01	-10000	0	-10000	0	0
STAT3	0.021	0.002	-10000	0	-10000	0	0
IL18RAP	0.033	0.033	0.12	76	-0.016	3	79
IL12RB1	-0.006	0.036	0.09	2	-0.056	1	3
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	-0.005	0.047	-10000	0	-0.19	1	1
IL23R/JAK2	-0.11	0.3	-10000	0	-1	50	50
positive regulation of chronic inflammatory response	-0.3	0.48	-10000	0	-1.1	127	127
natural killer cell activation	0.004	0.007	-10000	0	-10000	0	0
JAK2	-0.005	0.045	0.1	10	-0.068	5	15
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
NFKB1	0.012	0.017	-10000	0	-10000	0	0
RELA	0.012	0.017	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.26	0.42	-10000	0	-1.1	85	85
ALOX12B	-0.34	0.49	-10000	0	-1.1	158	158
CXCL1	-0.28	0.44	-10000	0	-1.1	105	105
T cell proliferation	-0.3	0.48	-10000	0	-1.1	127	127
NFKBIA	0.012	0.019	0.13	3	-10000	0	3
IL17A	-0.14	0.23	-10000	0	-0.53	97	97
PI3K	-0.27	0.45	-10000	0	-1	127	127
IFNG	-0.006	0.025	0.076	2	-0.091	19	21
STAT3 (dimer)	-0.26	0.43	-10000	0	-0.99	127	127
IL18R1	0.024	0.016	0.12	16	-10000	0	16
IL23/IL23R/JAK2/TYK2/SOCS3	-0.18	0.3	-10000	0	-0.74	89	89
IL18/IL18R	0.056	0.036	0.19	22	-0.13	3	25
macrophage activation	-0.015	0.02	-10000	0	-0.044	82	82
TNF	-0.3	0.48	-10000	0	-1.2	95	95
STAT3/STAT4	-0.32	0.46	-10000	0	-1.1	137	137
STAT4 (dimer)	-0.33	0.48	-10000	0	-1.1	137	137
IL18	0.026	0.021	0.12	29	-10000	0	29
IL19	-0.26	0.42	-10000	0	-1	99	99
STAT5A (dimer)	-0.28	0.47	-10000	0	-1.1	127	127
STAT1	0.022	0.011	0.12	7	-10000	0	7
SOCS3	0.021	0.017	0.12	14	-10000	0	14
CXCL9	-0.26	0.42	-10000	0	-1	98	98
MPO	-0.42	0.56	-10000	0	-1.1	238	238
positive regulation of humoral immune response	-0.3	0.48	-10000	0	-1.1	127	127
IL23/IL23R/JAK2/TYK2	-0.31	0.51	-10000	0	-1.2	125	125
IL6	-0.32	0.53	0.54	1	-1.2	143	144
STAT5A	0.021	0.002	-10000	0	-10000	0	0
IL2	0.011	0.016	-10000	0	-0.024	11	11
positive regulation of tyrosine phosphorylation of STAT protein	0.004	0.007	-10000	0	-10000	0	0
CD3E	-0.26	0.43	-10000	0	-1.1	96	96
keratinocyte proliferation	-0.3	0.48	-10000	0	-1.1	127	127
NOS2	-0.27	0.43	-10000	0	-1.1	105	105

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.015	0.025	0.14	4	-0.092	6	10
BUB1B	0.011	0.043	0.1	32	-0.13	7	39
PLK1	-0.009	0.042	0.079	30	-0.077	145	175
PLK1S1	-0.001	0.03	0.098	4	-0.2	5	9
KIF2A	-0.011	0.044	0.19	8	-0.099	15	23
regulation of mitotic centrosome separation	-0.009	0.042	0.08	29	-0.077	145	174
GOLGA2	0.021	0.003	-10000	0	-10000	0	0
Hec1/SPC24	0.062	0.085	0.16	168	-0.098	7	175
WEE1	0.013	0.072	0.15	9	-0.3	19	28
cytokinesis	0.019	0.047	0.15	8	-0.16	6	14
PP2A-alpha B56	0.071	0.069	-10000	0	-0.51	6	6
AURKA	0.007	0.029	0.098	6	-10000	0	6
PICH/PLK1	0.018	0.066	0.1	169	-0.088	10	179
CENPE	-0.01	0.04	0.082	15	-0.095	25	40
RhoA/GTP	0.015	0.002	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.011	0.044	0.19	8	-0.099	15	23
PPP2CA	0.021	0.002	-10000	0	-10000	0	0
FZR1	0.02	0.004	-10000	0	-10000	0	0
TPX2	0.01	0.034	0.11	24	-10000	0	24
PAK1	0.015	0.009	-10000	0	-10000	0	0
SPC24	0.044	0.044	0.12	154	-10000	0	154
FBXW11	0.021	0.003	-10000	0	-10000	0	0
CLSPN	-0.018	0.082	0.1	5	-0.25	65	70
GORASP1	0.021	0.002	-10000	0	-10000	0	0
metaphase	0	0.002	0.014	4	-0.01	2	6
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	-0.007	0.022	0.043	30	-0.041	147	177
G2 phase of mitotic cell cycle	0	0.002	0.012	10	-10000	0	10
STAG2	0.021	0.001	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.011	0.051	-10000	0	-0.51	6	6
spindle elongation	-0.009	0.042	0.08	29	-0.077	145	174
ODF2	0.022	0.004	-10000	0	-10000	0	0
BUB1	0.064	0.069	-10000	0	-0.55	6	6
TPT1	-0.009	0.044	0.1	1	-0.19	28	29
CDC25C	0.023	0.044	0.13	1	-0.24	6	7
CDC25B	0.021	0.006	-10000	0	-0.02	4	4
SGOL1	0.015	0.025	0.092	6	-0.14	4	10
RHOA	0.021	0.003	-10000	0	-10000	0	0
CCNB1/CDK1	0.03	0.052	0.13	58	-0.12	6	64
CDC14B	-0.006	0.004	0.015	1	-10000	0	1
CDC20	0.064	0.053	0.12	286	-10000	0	286
PLK1/PBIP1	0.003	0.039	0.073	37	-0.079	24	61
mitosis	-0.003	0.003	0.016	2	-10000	0	2
FBXO5	-0.007	0.038	0.11	15	-0.11	12	27
CDC2	0.001	0.002	-10000	0	-0.01	6	6
NDC80	0.098	0.046	0.12	494	-10000	0	494
metaphase plate congression	-0.02	0.079	-10000	0	-0.25	64	64
ERCC6L	0.025	0.061	0.14	82	-0.12	5	87
NLP/gamma Tubulin	-0.007	0.026	0.057	11	-0.064	31	42
microtubule cytoskeleton organization	-0.009	0.044	0.1	1	-0.19	28	29
G2/M transition DNA damage checkpoint	0.002	0.005	0.009	154	-10000	0	154
PPP1R12A	0.021	0.003	-10000	0	-10000	0	0
interphase	0.002	0.005	0.009	154	-10000	0	154
PLK1/PRC1-2	0.049	0.074	0.13	156	-0.094	14	170
GRASP65/GM130/RAB1/GTP/PLK1	0.014	0.05	-10000	0	-0.11	2	2
RAB1A	0.021	0.002	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	-0.005	0.032	0.076	32	-0.067	31	63
mitotic prometaphase	0.002	0.005	0.018	64	-10000	0	64
proteasomal ubiquitin-dependent protein catabolic process	0.008	0.043	0.16	3	-0.22	13	16
microtubule-based process	0.04	0.069	0.1	321	-0.076	80	401
Golgi organization	-0.009	0.042	0.08	29	-0.077	145	174
Cohesin/SA2	0.003	0.038	0.084	7	-0.084	6	13
PPP1CB/MYPT1	0.032	0.005	-10000	0	-10000	0	0
KIF20A	0.09	0.049	0.12	439	-10000	0	439
APC/C/CDC20	0.033	0.064	0.1	240	-0.069	95	335
PPP2R1A	0.019	0.007	-10000	0	-10000	0	0
chromosome segregation	0.003	0.039	0.072	37	-0.078	24	61
PRC1	0.025	0.02	0.12	26	-10000	0	26
ECT2	-0.01	0.044	0.15	14	-0.095	26	40
C13orf34	-0.008	0.035	0.07	30	-0.064	146	176
NUDC	-0.02	0.079	-10000	0	-0.25	64	64
regulation of attachment of spindle microtubules to kinetochore	0.011	0.042	0.1	32	-0.13	7	39
spindle assembly	-0.01	0.035	0.064	31	-0.066	144	175
spindle stabilization	-0.001	0.03	0.098	4	-0.2	5	9
APC/C/HCDH1	0.017	0.004	-10000	0	-10000	0	0
MKLP2/PLK1	0.041	0.07	0.1	321	-0.076	80	401
CCNB1	0.032	0.032	0.13	69	-0.02	2	71
PPP1CB	0.022	0.002	-10000	0	-10000	0	0
BTRC	0.019	0.006	-10000	0	-10000	0	0
ROCK2	0	0.042	-10000	0	-0.29	6	6
TUBG1	-0.001	0.024	-10000	0	-0.25	1	1
G2/M transition of mitotic cell cycle	0.001	0.033	-10000	0	-0.12	6	6
MLF1IP	0.018	0.027	0.049	289	-10000	0	289
INCENP	0.022	0.003	-10000	0	-10000	0	0

×

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	0.034	0.043	0.13	106	-10000	0	106
CDKN2C	0.041	0.043	0.11	172	-0.075	1	173
CDKN2A	0.044	0.052	0.13	180	-10000	0	180
CCND2	-0.009	0.021	0.077	1	-0.11	8	9
RB1	0.001	0.032	0.17	1	-0.16	5	6
CDK4	-0.01	0.024	0.098	2	-0.14	7	9
CDK6	-0.009	0.024	0.096	3	-0.14	6	9
G1/S progression	0.015	0.064	0.17	74	-0.26	3	77

×

Thromboxane A2 receptor 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
TGM2	0.02	0.007	0.13	2	-10000	0	2
GNB1/GNG2	-0.054	0.072	-10000	0	-0.18	152	152
AKT1	-0.041	0.11	0.24	15	-0.29	25	40
EGF	0.024	0.019	0.12	22	-10000	0	22
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	-0.003	0.057	0.22	31	-10000	0	31
mol:Ca2+	-0.047	0.14	0.28	14	-0.28	153	167
LYN	-0.007	0.061	0.22	33	-10000	0	33
RhoA/GTP	-0.027	0.056	0.093	2	-0.13	121	123
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.065	0.16	0.27	14	-0.33	153	167
GNG2	0.02	0.004	-10000	0	-10000	0	0
ARRB2	0.021	0.002	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.004	0.062	-10000	0	-0.46	7	7
G beta5/gamma2	-0.062	0.097	-10000	0	-0.23	150	150
PRKCH	-0.058	0.16	0.28	14	-0.32	154	168
DNM1	0.009	0.01	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin3	0	0.023	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	0.024	0.02	0.12	25	-10000	0	25
G12 family/GTP	-0.064	0.12	-10000	0	-0.29	126	126
ADRBK1	0.021	0.003	-10000	0	-10000	0	0
ADRBK2	0.02	0.004	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0.027	0.006	0.096	1	-10000	0	1
mol:GDP	0.026	0.097	0.27	14	-0.24	15	29
mol:NADP	0.017	0.01	0.12	1	-10000	0	1
RAB11A	0.021	0.003	-10000	0	-10000	0	0
PRKG1	0.019	0.009	0.12	2	-10000	0	2
mol:IP3	-0.062	0.17	0.31	12	-0.34	153	165
cell morphogenesis	0.027	0.006	0.095	1	-10000	0	1
PLCB2	-0.089	0.22	0.36	8	-0.46	153	161
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	0.001	0.064	0.22	34	-10000	0	34
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.011	0.048	0.19	23	-10000	0	23
RHOA	0.021	0.003	-10000	0	-10000	0	0
PTGIR	0.021	0.017	0.12	14	-10000	0	14
PRKCB1	-0.062	0.17	0.29	12	-0.34	155	167
GNAQ	0.021	0.003	-10000	0	-10000	0	0
mol:L-citrulline	0.017	0.01	0.12	1	-10000	0	1
TXA2/TXA2-R family	-0.1	0.23	0.34	9	-0.49	155	164
LCK	0.009	0.064	0.23	33	-10000	0	33
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.013	0.03	0.16	1	-10000	0	1
TXA2-R family/G12 family/GDP/G beta/gamma	-0.027	0.14	-10000	0	-0.42	68	68
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.015	0.031	0.16	1	-10000	0	1
MAPK14	-0.042	0.11	0.21	16	-0.22	149	165
TGM2/GTP	-0.074	0.18	0.32	7	-0.39	150	157
MAPK11	-0.043	0.11	0.21	17	-0.22	150	167
ARHGEF1	-0.038	0.075	0.13	2	-0.17	121	123
GNAI2	0.021	0.003	-10000	0	-10000	0	0
JNK cascade	-0.073	0.18	0.3	13	-0.36	155	168
RAB11/GDP	0.02	0.006	-10000	0	-0.023	9	9
ICAM1	-0.051	0.13	0.24	15	-0.27	154	169
cAMP biosynthetic process	-0.064	0.16	0.3	12	-0.32	152	164
Gq family/GTP/EBP50	0.01	0.03	0.24	6	-0.17	9	15
actin cytoskeleton reorganization	0.027	0.006	0.095	1	-10000	0	1
SRC	-0.012	0.047	0.19	23	-10000	0	23
GNB5	0.021	0.003	-10000	0	-10000	0	0
GNB1	0.019	0.007	-10000	0	-10000	0	0
EGF/EGFR	0.023	0.083	0.22	54	-0.19	9	63
VCAM1	-0.054	0.14	0.24	15	-0.28	154	169
TP beta/Gq family/GDP/G beta5/gamma2	0.004	0.062	-10000	0	-0.46	7	7
platelet activation	-0.054	0.14	0.28	15	-0.28	153	168
PGI2/IP	0.015	0.012	0.09	14	-10000	0	14
PRKACA	0.011	0.008	-10000	0	-10000	0	0
Gq family/GDP/G beta5/gamma2	0.006	0.05	-10000	0	-0.38	6	6
TXA2/TP beta/beta Arrestin2	-0.2	0.2	-10000	0	-0.39	335	335
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.002	0.016	-10000	0	-10000	0	0
mol:DAG	-0.069	0.19	0.32	12	-0.38	154	166
EGFR	0.053	0.054	0.12	235	-10000	0	235
TXA2/TP alpha	-0.088	0.21	0.35	11	-0.44	152	163
Gq family/GTP	0.005	0.026	0.21	4	-0.19	6	10
YES1	-0.006	0.061	0.22	33	-10000	0	33
GNAI2/GTP	0.002	0.031	-10000	0	-0.12	1	1
PGD2/DP	0.017	0.015	0.089	25	-10000	0	25
SLC9A3R1	0.021	0.003	-10000	0	-10000	0	0
FYN	-0.006	0.06	0.22	33	-10000	0	33
mol:NO	0.017	0.01	0.12	1	-10000	0	1
GNA15	0.021	0.006	0.12	1	-10000	0	1
PGK/cGMP	0.02	0.019	0.097	3	-0.13	6	9
RhoA/GDP	0.02	0.006	-10000	0	-0.023	9	9
TP alpha/TGM2/GDP/G beta/gamma	0.027	0.035	0.17	3	-0.16	1	4
NOS3	0.017	0.01	0.12	1	-10000	0	1
RAC1	0.018	0.008	-10000	0	-10000	0	0
PRKCA	-0.056	0.16	0.29	13	-0.32	143	156
PRKCB	-0.076	0.16	0.25	8	-0.34	160	168
PRKCE	-0.058	0.16	0.29	11	-0.32	151	162
PRKCD	-0.066	0.17	0.28	13	-0.36	158	171
PRKCG	-0.084	0.17	0.32	9	-0.38	156	165
muscle contraction	-0.098	0.21	0.33	9	-0.46	156	165
PRKCZ	-0.072	0.16	0.27	14	-0.33	154	168
ARR3	0.016	0.001	-10000	0	-10000	0	0
TXA2/TP beta	0.009	0.036	0.16	3	-0.12	1	4
PRKCQ	-0.061	0.16	0.27	17	-0.33	152	169
MAPKKK cascade	-0.084	0.2	0.32	10	-0.41	155	165
SELE	-0.07	0.16	0.24	15	-0.35	154	169
TP beta/GNAI2/GDP/G beta/gamma	0.028	0.035	0.17	4	-0.15	1	5
ROCK1	0.021	0.005	0.12	1	-10000	0	1
GNA14	0.021	0.003	-10000	0	-10000	0	0
chemotaxis	-0.12	0.26	0.35	8	-0.58	154	162
GNA12	0.018	0.008	-10000	0	-10000	0	0
GNA13	0.02	0.004	-10000	0	-10000	0	0
GNA11	0.02	0.004	-10000	0	-10000	0	0
Rac1/GTP	0.013	0.006	-10000	0	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.021	0.016	0.12	12	0	72	84
ITGB7	0.022	0.012	0.12	8	-9999	0	8
ITGA4	0.036	0.036	0.12	95	-9999	0	95
alpha4/beta7 Integrin	0.042	0.029	0.18	4	-9999	0	4
alpha4/beta1 Integrin	0.038	0.031	0.12	78	-9999	0	78

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.012	0.041	-10000	0	-0.13	48	48
ARNO/beta Arrestin1-2	-0.045	0.24	-10000	0	-0.75	67	67
EGFR	0.053	0.054	0.12	235	-10000	0	235
EPHA2	0.02	0.013	0.12	8	-10000	0	8
USP6	0.021	0.007	0.12	3	-10000	0	3
IQSEC1	0.021	0.003	-10000	0	-10000	0	0
EGFR/EGFR/EGF/EGF	0.05	0.045	0.11	237	-10000	0	237
ARRB2	0.008	0.004	-10000	0	-10000	0	0
mol:GTP	-0.003	0.042	0.12	6	-0.12	44	50
ARRB1	0.02	0.004	-10000	0	-10000	0	0
FBXO8	0.021	0.006	0.12	1	-10000	0	1
TSHR	0.079	0.053	0.12	374	-10000	0	374
EGF	0.024	0.019	0.12	22	-10000	0	22
somatostatin receptor activity	0	0	0.001	115	-0.001	8	123
ARAP2	0.021	0.003	-10000	0	-10000	0	0
mol:GDP	0.032	0.092	0.19	101	-0.25	16	117
mol:PI-3-4-5-P3	0	0	0.001	133	-0.001	4	137
ITGA2B	0.021	0.003	-10000	0	-10000	0	0
ARF6	0.021	0.004	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.048	0.02	-10000	0	-10000	0	0
ADAP1	0.016	0.009	-10000	0	-10000	0	0
KIF13B	0.021	0.003	-10000	0	-10000	0	0
HGF/MET	-0.042	0.089	0.11	6	-0.16	232	238
PXN	0.021	0.002	-10000	0	-10000	0	0
ARF6/GTP	0.05	0.1	0.24	107	-0.23	10	117
EGFR/EGFR/EGF/EGF/ARFGEP100	0.054	0.048	0.18	4	-0.13	5	9
ADRB2	0.021	0.003	-10000	0	-10000	0	0
receptor agonist activity	0	0	0	95	0	9	104
actin filament binding	0	0	0.001	109	0	8	117
SRC	0.02	0.004	-10000	0	-10000	0	0
ITGB3	0.04	0.04	0.12	124	-10000	0	124
GNAQ	0.021	0.003	-10000	0	-10000	0	0
EFA6/PI-4-5-P2	0	0.001	0.002	135	-0.001	8	143
ARF6/GDP	-0.01	0.1	0.19	4	-0.31	41	45
ARF6/GDP/GULP/ACAP1	0.047	0.09	0.2	69	-0.26	15	84
alphaIIb/beta3 Integrin/paxillin/GIT1	0.063	0.033	-10000	0	-0.12	7	7
ACAP1	0.022	0.009	0.12	5	-10000	0	5
ACAP2	0.021	0.004	-10000	0	-10000	0	0
LHCGR/beta Arrestin2	0.018	0.01	0.11	6	-10000	0	6
EFNA1	0.021	0.003	-10000	0	-10000	0	0
HGF	0.018	0.013	0.12	5	-10000	0	5
CYTH3	-0.005	0.002	-10000	0	-10000	0	0
CYTH2	-0.083	0.29	-10000	0	-0.95	67	67
NCK1	0.021	0.005	0.12	1	-10000	0	1
fibronectin binding	0	0	0.001	113	0	8	121
endosomal lumen acidification	0	0	0.001	114	0	7	121
microtubule-based process	0	0	-10000	0	0	17	17
GULP1	0.021	0.006	0.12	1	-10000	0	1
GNAQ/ARNO	-0.064	0.27	-10000	0	-0.88	67	67
mol:Phosphatidic acid	0	0	0	38	-10000	0	38
PIP3-E	0	0	0	87	0	1	88
MET	0.009	0.011	0.12	1	-10000	0	1
GNA14	0.021	0.003	-10000	0	-10000	0	0
GNA15	0.021	0.006	0.12	1	-10000	0	1
GIT1	0.021	0.002	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	0.001	117	-0.001	8	125
GNA11	0.02	0.004	-10000	0	-10000	0	0
LHCGR	0.02	0.01	0.12	6	-10000	0	6
AGTR1	0.027	0.024	0.12	37	-10000	0	37
desensitization of G-protein coupled receptor protein signaling pathway	0.018	0.01	0.11	6	-10000	0	6
IPCEF1/ARNO	-0.037	0.26	-10000	0	-0.78	67	67
alphaIIb/beta3 Integrin	0.043	0.036	0.11	123	-0.15	7	130

×

HIF-1-alpha transcription factor network

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
PKM2	0.076	0.11	0.24	64	-0.4	8	72
HDAC7	0.021	0.004	-10000	0	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	0.15	0.2	0.38	93	-0.57	31	124
SMAD4	0.021	0.003	-10000	0	-10000	0	0
ID2	0.087	0.11	0.28	45	-0.44	6	51
AP1	0.026	0.023	0.12	2	-0.15	7	9
ABCG2	0.088	0.11	0.28	49	-0.44	6	55
HIF1A	0.041	0.032	0.11	33	-10000	0	33
TFF3	0.09	0.12	0.28	60	-0.43	6	66
GATA2	0.022	0.009	0.12	4	-10000	0	4
AKT1	0.036	0.048	0.11	27	-0.15	29	56
response to hypoxia	0.019	0.042	0.072	62	-0.14	32	94
MCL1	0.086	0.11	0.28	40	-0.44	6	46
NDRG1	0.082	0.11	0.28	46	-0.44	6	52
SERPINE1	0.076	0.12	0.29	68	-0.41	6	74
FECH	0.086	0.11	0.28	48	-0.44	6	54
FURIN	0.087	0.11	0.28	47	-0.43	6	53
NCOA2	0.022	0.006	-10000	0	-10000	0	0
EP300	0.028	0.076	0.13	10	-0.29	31	41
HMOX1	0.091	0.12	0.29	64	-0.44	5	69
BHLHE40	0.087	0.12	0.28	46	-0.44	8	54
BHLHE41	0.085	0.11	0.28	43	-0.44	7	50
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.096	0.055	0.21	36	-10000	0	36
ENG	0.031	0.048	0.22	24	-10000	0	24
JUN	0.019	0.007	-10000	0	-10000	0	0
RORA	0.087	0.11	0.28	45	-0.43	6	51
ABCB1	0.037	0.049	-10000	0	-0.4	2	2
TFRC	0.086	0.11	0.28	42	-0.46	5	47
CXCR4	0.1	0.12	0.3	81	-0.44	6	87
TF	0.085	0.12	0.28	42	-0.48	6	48
CITED2	0.085	0.11	0.28	43	-0.46	5	48
HIF1A/ARNT	0.23	0.2	0.51	129	-0.68	2	131
LDHA	0.039	0.079	-10000	0	-0.56	5	5
ETS1	0.09	0.11	0.28	52	-0.43	6	58
PGK1	0.088	0.11	0.28	49	-0.44	6	55
NOS2	0.09	0.12	0.29	49	-0.43	7	56
ITGB2	0.087	0.12	0.28	50	-0.44	6	56
ALDOA	0.088	0.11	0.28	45	-0.44	6	51
Cbp/p300/CITED2	0.09	0.18	0.31	57	-0.6	31	88
FOS	0.021	0.013	0.13	8	-10000	0	8
HK2	0.09	0.12	0.28	47	-0.45	6	53
SP1	0.023	0.004	-10000	0	-10000	0	0
GCK	-0.004	0.27	-10000	0	-1.2	32	32
HK1	0.075	0.11	0.27	39	-0.44	6	45
NPM1	0.088	0.11	0.28	48	-0.44	6	54
EGLN1	0.086	0.11	0.27	45	-0.44	6	51
CREB1	0.023	0.001	-10000	0	-10000	0	0
PGM1	0.082	0.11	0.27	46	-0.48	4	50
SMAD3	0.021	0.003	-10000	0	-10000	0	0
EDN1	0.016	0.11	-10000	0	-0.48	15	15
IGFBP1	0.086	0.12	0.29	59	-0.42	5	64
VEGFA	0.078	0.16	0.29	62	-0.51	31	93
HIF1A/JAB1	0.047	0.027	0.12	14	-10000	0	14
CP	0.097	0.13	0.29	77	-0.47	7	84
CXCL12	0.076	0.11	0.28	37	-0.44	6	43
COPS5	0.022	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4	0.031	0.006	-10000	0	-10000	0	0
BNIP3	0.074	0.11	0.28	35	-0.44	6	41
EGLN3	0.087	0.11	0.28	47	-0.43	6	53
CA9	0.1	0.12	0.29	94	-0.44	6	100
TERT	0.11	0.13	0.29	92	-0.45	5	97
ENO1	0.079	0.11	0.27	43	-0.48	4	47
PFKL	0.086	0.11	0.28	47	-0.44	6	53
NCOA1	0.021	0.002	-10000	0	-10000	0	0
ADM	0.09	0.12	0.3	60	-0.44	8	68
ARNT	0.04	0.03	0.11	23	-10000	0	23
HNF4A	0.012	0.028	0.12	1	-0.11	29	30
ADFP	0.076	0.11	0.24	64	-0.4	8	72
SLC2A1	0.064	0.15	0.27	36	-0.5	31	67
LEP	0.065	0.1	0.27	30	-0.41	6	36
HIF1A/ARNT/Cbp/p300	0.14	0.2	0.38	91	-0.59	31	122
EPO	0.075	0.12	0.33	36	-0.55	5	41
CREBBP	0.029	0.079	0.13	10	-0.3	32	42
HIF1A/ARNT/Cbp/p300/HDAC7	0.14	0.2	0.4	91	-0.57	31	122
PFKFB3	0.074	0.11	0.27	37	-0.44	6	43
NT5E	0.088	0.12	0.29	45	-0.44	6	51

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.019	0.008	0.12	1	-10000	0	1
CCL5	0.036	0.037	0.12	97	-10000	0	97
SDCBP	0.02	0.004	-10000	0	-10000	0	0
FGFR/FGF2/Syndecan-1	0.029	0.05	0.18	20	-10000	0	20
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
Syndecan-1/Laminin-5	0.035	0.054	0.18	17	-0.21	6	23
Syndecan-1/Syntenin	0.041	0.062	0.21	30	-0.21	6	36
MAPK3	0.028	0.051	0.16	21	-0.2	6	27
HGF/MET	-0.042	0.089	0.11	6	-0.16	232	238
TGFB1/TGF beta receptor Type II	0.019	0.008	0.12	1	-10000	0	1
BSG	0.02	0.004	-10000	0	-10000	0	0
keratinocyte migration	0.034	0.053	0.18	17	-0.2	6	23
Syndecan-1/RANTES	0.052	0.072	0.18	81	-0.22	7	88
Syndecan-1/CD147	0.046	0.057	0.2	17	-0.2	6	23
Syndecan-1/Syntenin/PIP2	0.039	0.058	0.2	30	-0.2	6	36
LAMA5	0.02	0.006	0.12	1	-10000	0	1
positive regulation of cell-cell adhesion	0.037	0.056	0.19	29	-0.2	6	35
MMP7	0.057	0.051	0.12	238	-10000	0	238
HGF	0.018	0.013	0.12	5	-10000	0	5
Syndecan-1/CASK	0.02	0.046	0.12	28	-0.2	6	34
Syndecan-1/HGF/MET	-0.006	0.08	0.19	9	-0.19	35	44
regulation of cell adhesion	0.021	0.068	0.22	35	-0.19	6	41
HPSE	0.043	0.043	0.12	141	-10000	0	141
positive regulation of cell migration	0.029	0.05	0.18	20	-10000	0	20
SDC1	0.031	0.041	0.14	30	-0.14	2	32
Syndecan-1/Collagen	0.029	0.05	0.18	20	-10000	0	20
PPIB	0.021	0.008	0.12	4	-10000	0	4
MET	0.009	0.011	0.12	1	-10000	0	1
PRKACA	0.02	0.004	-10000	0	-10000	0	0
MMP9	0.05	0.048	0.12	193	-10000	0	193
MAPK1	0.027	0.051	0.16	20	-0.2	6	26
homophilic cell adhesion	0.03	0.057	0.2	26	-0.18	5	31
MMP1	0.035	0.039	0.12	105	-10000	0	105

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	-0.014	0.027	0.2	4	-0.2	6	10
RFC1	-0.015	0.019	-10000	0	-0.2	4	4
PRKDC	-0.012	0.034	0.2	10	-0.2	5	15
RIPK1	0.022	0.005	-10000	0	-0.019	3	3
CASP7	-0.074	0.19	-10000	0	-0.59	75	75
FASLG/FAS/FADD/FAF1	-0.025	0.048	-10000	0	-0.13	31	31
MAP2K4	-0.069	0.13	0.19	1	-0.3	120	121
mol:ceramide	-0.027	0.084	-10000	0	-0.2	64	64
GSN	-0.014	0.027	0.2	4	-0.2	6	10
FASLG/FAS/FADD/FAF1/Caspase 8	-0.018	0.053	-10000	0	-0.21	13	13
FAS	0.016	0.028	0.13	25	-0.029	100	125
BID	-0.032	0.023	-10000	0	-10000	0	0
MAP3K1	-0.071	0.14	-10000	0	-0.39	77	77
MAP3K7	0.014	0.015	-10000	0	-0.019	100	100
RB1	-0.014	0.023	0.22	2	-0.2	4	6
CFLAR	0.022	0.005	-10000	0	-0.019	3	3
HGF/MET	-0.029	0.082	-10000	0	-0.14	232	232
ARHGDIB	-0.009	0.04	0.21	16	-0.19	5	21
FADD	0.013	0.018	-10000	0	-0.029	100	100
actin filament polymerization	0.018	0.039	0.18	22	-0.2	6	28
NFKB1	-0.021	0.11	-10000	0	-0.76	8	8
MAPK8	-0.094	0.18	-10000	0	-0.44	116	116
DFFA	-0.014	0.022	0.22	1	-0.2	4	5
DNA fragmentation during apoptosis	-0.016	0.032	0.2	2	-0.18	16	18
FAS/FADD/MET	-0.031	0.081	0.18	1	-0.14	231	232
CFLAR/RIP1	0.033	0.008	-10000	0	-10000	0	0
FAIM3	0.046	0.044	0.12	158	-10000	0	158
FAF1	0.012	0.019	-10000	0	-0.036	74	74
PARP1	-0.015	0.023	0.22	1	-0.2	6	7
DFFB	-0.013	0.023	0.2	2	-0.2	4	6
CHUK	-0.022	0.1	-10000	0	-0.72	8	8
FASLG	0.014	0.027	0.12	17	-0.035	104	121
FAS/FADD	0.021	0.031	0.11	25	-0.062	1	26
HGF	0.018	0.013	0.12	5	-10000	0	5
LMNA	-0.019	0.032	0.19	4	-0.17	17	21
CASP6	-0.014	0.02	-10000	0	-0.19	5	5
CASP10	0.014	0.018	-10000	0	-0.029	103	103
CASP3	-0.012	0.019	-10000	0	-0.24	2	2
PTPN13	0.021	0.005	0.12	1	-10000	0	1
CASP8	-0.034	0.028	-10000	0	-10000	0	0
IL6	-0.18	0.41	-10000	0	-1.1	109	109
MET	0.009	0.011	0.12	1	-10000	0	1
ICAD/CAD	-0.015	0.026	0.29	2	-0.19	4	6
FASLG/FAS/FADD/FAF1/Caspase 10	-0.028	0.085	-10000	0	-0.21	64	64
activation of caspase activity by cytochrome c	-0.032	0.023	-10000	0	-10000	0	0
PAK2	-0.014	0.031	0.21	6	-0.2	6	12
BCL2	0.021	0.003	-10000	0	-10000	0	0

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.039	0.039	-10000	0	-0.1	28	28
NF kappa B1 p50/RelA/I kappa B alpha	-0.032	0.1	0.22	16	-0.22	26	42
AP1	-0.006	0.063	-10000	0	-0.11	120	120
mol:PIP3	-0.019	0.041	-10000	0	-0.11	44	44
AKT1	0.002	0.071	0.23	21	-0.24	6	27
PTK2B	0.001	0.058	0.18	17	-0.18	23	40
RHOA	0.012	0.053	0.18	11	-0.34	4	15
PIK3CB	0.021	0.003	-10000	0	-0.022	2	2
mol:Ca2+	-0.029	0.066	0.18	20	-0.2	4	24
MAGI3	0.019	0.007	-10000	0	-10000	0	0
RELA	0.021	0.003	-10000	0	-10000	0	0
apoptosis	-0.026	0.07	-10000	0	-0.15	158	158
HRAS/GDP	0.015	0.003	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.005	0.056	0.18	19	-0.25	5	24
NF kappa B1 p50/RelA	-0.027	0.08	-10000	0	-0.19	29	29
endothelial cell migration	0.021	0.051	0.27	3	-0.13	5	8
ADCY4	0.002	0.068	0.12	42	-0.29	25	67
ADCY5	-0.003	0.072	0.12	37	-0.28	32	69
ADCY6	0.002	0.068	0.12	18	-0.29	25	43
ADCY7	0.003	0.066	0.12	45	-0.28	25	70
ADCY1	-0.027	0.082	0.13	10	-0.32	28	38
ADCY2	0.001	0.068	0.12	44	-0.29	25	69
ADCY3	0.003	0.067	0.12	48	-0.28	26	74
ADCY8	0.003	0.067	0.12	46	-0.28	25	71
ADCY9	0.003	0.066	0.12	47	-0.28	24	71
GSK3B	-0.002	0.056	0.18	17	-0.21	11	28
arachidonic acid secretion	0.002	0.071	0.12	1	-0.27	28	29
GNG2	0.02	0.005	-10000	0	-0.022	2	2
TRIP6	0.013	0.01	-10000	0	-10000	0	0
GNAO1	0.007	0.031	-10000	0	-0.12	29	29
HRAS	0.02	0.005	-10000	0	-10000	0	0
NFKBIA	-0.045	0.098	0.21	21	-0.2	115	136
GAB1	0.021	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	-0.005	0.17	-10000	0	-0.79	29	29
JUN	0.019	0.007	-10000	0	-10000	0	0
LPA/LPA2/NHERF2	0.031	0.011	0.11	1	-10000	0	1
TIAM1	-0.019	0.2	-10000	0	-0.96	29	29
PIK3R1	0.021	0.003	-10000	0	-0.019	1	1
mol:IP3	-0.031	0.062	0.16	16	-0.26	2	18
PLCB3	-0.006	0.012	-10000	0	-10000	0	0
FOS	0.021	0.013	0.12	8	-10000	0	8
positive regulation of mitosis	0.002	0.071	0.12	1	-0.27	28	29
LPA/LPA1-2-3	0.003	0.07	0.15	1	-0.11	163	164
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0.001	-10000	0	-10000	0	0
BCAR1	0.021	0.003	-10000	0	-10000	0	0
stress fiber formation	-0.001	0.065	0.2	13	-0.37	4	17
GNAZ	0.007	0.031	-10000	0	-0.12	28	28
EGFR/PI3K-beta/Gab1	-0.01	0.049	-10000	0	-0.12	4	4
positive regulation of dendritic cell cytokine production	0.002	0.069	0.15	1	-0.11	163	164
LPA/LPA2/MAGI-3	0.029	0.015	0.1	4	-10000	0	4
ARHGEF1	0.021	0.074	0.19	96	-10000	0	96
GNAI2	0.007	0.031	-10000	0	-0.12	28	28
GNAI3	0.011	0.021	-10000	0	-0.12	8	8
GNAI1	0.005	0.028	-10000	0	-0.12	24	24
LPA/LPA3	-0.021	0.067	-10000	0	-0.15	141	141
LPA/LPA2	0.02	0.011	0.092	7	-10000	0	7
LPA/LPA1	0.021	0.042	0.1	1	-0.15	29	30
HB-EGF/EGFR	0.043	0.043	0.098	205	-10000	0	205
HBEGF	0.006	0.029	0.051	188	-10000	0	188
mol:DAG	-0.031	0.062	0.16	16	-0.26	2	18
cAMP biosynthetic process	0.002	0.084	0.2	16	-0.28	29	45
NFKB1	0.021	0.002	-10000	0	-10000	0	0
SRC	0.02	0.004	-10000	0	-10000	0	0
GNB1	0.019	0.007	-10000	0	-10000	0	0
LYN	-0.039	0.097	0.2	25	-0.19	110	135
GNAQ	-0.024	0.064	-10000	0	-0.15	136	136
LPAR2	0.021	0.011	0.12	7	-0.023	1	8
LPAR3	0.01	0.011	-10000	0	-0.015	37	37
LPAR1	0.025	0.011	-10000	0	-10000	0	0
IL8	-0.032	0.18	0.32	19	-0.42	97	116
PTK2	-0.021	0.06	0.18	24	-0.2	1	25
Rac1/GDP	0.013	0.006	-10000	0	-10000	0	0
CASP3	-0.026	0.071	-10000	0	-0.15	158	158
EGFR	0.052	0.054	0.12	235	-10000	0	235
PLCG1	-0.034	0.07	0.15	5	-0.16	134	139
PLD2	-0.024	0.061	0.18	25	-0.2	1	26
G12/G13	0.035	0.038	-10000	0	-0.11	24	24
PI3K-beta	0.002	0.049	-10000	0	-0.2	19	19
cell migration	-0.004	0.055	-10000	0	-0.24	22	22
SLC9A3R2	0.021	0.002	-10000	0	-10000	0	0
PXN	-0.001	0.066	0.2	13	-0.38	4	17
HRAS/GTP	-0.004	0.069	0.11	40	-0.28	28	68
RAC1	0.018	0.008	-10000	0	-10000	0	0
MMP9	0.05	0.048	0.12	193	-0.015	2	195
PRKCE	0.02	0.005	-10000	0	-0.022	2	2
PRKCD	-0.028	0.076	0.21	26	-0.25	3	29
Gi(beta/gamma)	0	0.083	0.12	36	-0.3	27	63
mol:LPA	0.005	0.009	-10000	0	-10000	0	0
TRIP6/p130 Cas/FAK1/Paxillin	-0.003	0.065	0.18	2	-0.37	3	5
MAPKKK cascade	0.002	0.071	0.12	1	-0.27	28	29
contractile ring contraction involved in cytokinesis	0.012	0.063	0.22	19	-0.34	4	23
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.024	0.064	-10000	0	-0.15	136	136
GNA15	-0.024	0.064	-10000	0	-0.15	137	137
GNA12	0.018	0.008	-10000	0	-10000	0	0
GNA13	0.02	0.004	-10000	0	-10000	0	0
MAPT	-0.005	0.057	0.18	19	-0.26	5	24
GNA11	-0.024	0.064	-10000	0	-0.15	137	137
Rac1/GTP	-0.005	0.18	-10000	0	-0.84	29	29
MMP2	0.022	0.052	0.27	3	-0.13	5	8

×

S1P1 pathway

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
VEGFR2 homodimer/VEGFA homodimer	0.03	0.035	0.18	1	-10000	0	1
PDGFRB	0.017	0.016	0.12	4	-0.018	17	21
SPHK1	-0.002	0.056	-10000	0	-0.91	2	2
mol:S1P	-0.006	0.057	-10000	0	-0.83	2	2
S1P1/S1P/Gi	-0.035	0.13	0.2	2	-0.34	86	88
GNAO1	0.014	0.017	-10000	0	-0.028	88	88
PDGFB-D/PDGFRB/PLCgamma1	-0.024	0.13	0.19	5	-0.32	85	90
PLCG1	-0.037	0.12	0.18	2	-0.33	84	86
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.017	0.016	0.12	4	-0.018	17	21
GNAI2	0.015	0.017	-10000	0	-0.028	86	86
GNAI3	0.014	0.016	0.12	1	-0.027	66	67
GNAI1	0.012	0.016	-10000	0	-0.027	77	77
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	-0.008	0.017	0.058	1	-10000	0	1
S1P1/S1P	-0.008	0.065	-10000	0	-0.62	2	2
negative regulation of cAMP metabolic process	-0.034	0.12	0.2	2	-0.33	86	88
MAPK3	-0.062	0.18	0.21	1	-0.51	90	91
calcium-dependent phospholipase C activity	-0.001	0.003	-10000	0	-10000	0	0
Rac1/GDP	0.013	0.006	-10000	0	-10000	0	0
RhoA/GDP	0.015	0.002	-10000	0	-10000	0	0
KDR	0.016	0.019	0.12	8	-0.023	87	95
PLCB2	-0.001	0.069	0.18	16	-0.55	2	18
RAC1	0.018	0.008	-10000	0	-10000	0	0
RhoA/GTP	-0.007	0.056	-10000	0	-0.51	2	2
receptor internalization	-0.008	0.061	-10000	0	-0.57	2	2
PTGS2	-0.1	0.32	0.3	1	-0.9	89	90
Rac1/GTP	-0.008	0.053	-10000	0	-0.51	2	2
RHOA	0.021	0.003	-10000	0	-10000	0	0
VEGFA	0.027	0.039	0.12	79	-0.023	87	166
negative regulation of T cell proliferation	-0.034	0.12	0.2	2	-0.33	86	88
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	0.014	0.017	-10000	0	-0.027	88	88
MAPK1	-0.063	0.18	0.21	1	-0.51	91	92
S1P1/S1P/PDGFB-D/PDGFRB	0	0.079	0.18	11	-0.45	3	14
ABCC1	0.016	0.015	0.12	1	-0.022	79	80

×

Ceramide signaling pathway

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
SPHK2	-0.009	0.006	-10000	0	-10000	0	0
MAP4K4	-0.006	0.049	-10000	0	-0.25	9	9
BAG4	0.02	0.004	-10000	0	-10000	0	0
PKC zeta/ceramide	-0.029	0.12	-10000	0	-0.25	105	105
NFKBIA	0.021	0.008	0.12	3	-10000	0	3
BIRC3	0.023	0.017	0.12	16	-10000	0	16
BAX	-0.043	0.12	-10000	0	-0.35	76	76
RIPK1	0.021	0.003	-10000	0	-10000	0	0
AKT1	0	0.05	0.68	3	-10000	0	3
BAD	-0.035	0.1	0.19	5	-0.22	106	111
SMPD1	-0.002	0.046	0.12	10	-0.17	17	27
RB1	-0.036	0.1	0.19	2	-0.22	108	110
FADD/Caspase 8	0	0.054	0.19	1	-0.3	8	9
MAP2K4	-0.038	0.095	0.18	1	-0.22	107	108
NSMAF	0.02	0.004	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.037	0.098	0.18	7	-0.22	106	113
EGF	0.024	0.019	0.12	22	-10000	0	22
mol:ceramide	-0.035	0.11	-10000	0	-0.23	108	108
MADD	0.02	0.004	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.01	0.005	-10000	0	-10000	0	0
ASAH1	0.02	0.004	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.036	0.1	0.19	2	-0.22	108	110
cell proliferation	-0.017	0.087	0.17	3	-0.19	101	104
BID	-0.005	0.11	-10000	0	-0.68	12	12
MAP3K1	-0.036	0.1	0.2	1	-0.22	108	109
EIF2A	-0.039	0.092	0.17	5	-0.21	107	112
TRADD	0.021	0.002	-10000	0	-10000	0	0
CRADD	0.021	0.002	-10000	0	-10000	0	0
MAPK3	-0.032	0.086	0.17	6	-0.2	98	104
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.034	0.089	0.17	6	-0.21	100	106
Cathepsin D/ceramide	-0.022	0.11	-10000	0	-0.22	106	106
FADD	-0.005	0.048	-10000	0	-0.25	8	8
KSR1	-0.036	0.1	0.2	1	-0.22	106	107
MAPK8	-0.078	0.15	-10000	0	-0.25	216	216
PRKRA	-0.037	0.1	0.2	1	-0.22	108	109
PDGFA	0.018	0.008	-10000	0	-10000	0	0
TRAF2	0.021	0.003	-10000	0	-10000	0	0
IGF1	0.021	0.005	0.12	1	-10000	0	1
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.035	0.11	-10000	0	-0.23	108	108
CTSD	0.02	0.005	-10000	0	-10000	0	0
regulation of nitric oxide biosynthetic process	0.03	0.005	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.018	0.094	0.18	3	-0.21	101	104
PRKCD	0.02	0.004	-10000	0	-10000	0	0
PRKCZ	0.016	0.009	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.01	0.005	-10000	0	-10000	0	0
RelA/NF kappa B1	0.03	0.005	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.023	0.016	0.12	15	-10000	0	15
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0	0.05	-10000	0	-0.26	7	7
TNFR1A/BAG4/TNF-alpha	0.028	0.049	-10000	0	-0.14	49	49
mol:Sphingosine-1-phosphate	-0.009	0.006	-10000	0	-10000	0	0
MAP2K1	-0.038	0.093	0.17	8	-0.21	105	113
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.021	0.003	-10000	0	-10000	0	0
CYCS	-0.022	0.071	0.19	1	-0.2	77	78
TNFRSF1A	0.021	0.01	0.12	5	-10000	0	5
NFKB1	0.021	0.002	-10000	0	-10000	0	0
TNFR1A/BAG4	0.027	0.022	-10000	0	-0.16	7	7
EIF2AK2	-0.038	0.097	0.17	4	-0.22	108	112
TNF-alpha/TNFR1A/FAN	0.029	0.046	-10000	0	-0.13	43	43
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.015	0.057	-10000	0	-0.41	6	6
MAP2K2	-0.034	0.086	0.17	11	-0.21	98	109
SMPD3	-0.006	0.067	-10000	0	-0.26	27	27
TNF	0.021	0.015	0.12	11	-10000	0	11
PKC zeta/PAR4	0.008	0.059	0.11	11	-0.16	72	83
mol:PHOSPHOCHOLINE	-0.019	0.062	0.11	6	-0.15	103	109
NF kappa B1/RelA/I kappa B alpha	0.035	0.058	-10000	0	-0.12	71	71
AIFM1	-0.035	0.083	0.19	1	-0.17	135	136
BCL2	0.021	0.003	-10000	0	-10000	0	0

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.02	0.004	-10000	0	-10000	0	0
VLDLR	0.02	0.006	-10000	0	-10000	0	0
LRPAP1	0.021	0.003	-10000	0	-10000	0	0
NUDC	0.019	0.006	-10000	0	-10000	0	0
RELN/LRP8	-0.017	0.073	-10000	0	-0.13	189	189
CaM/Ca2+	0.015	0.003	-10000	0	-10000	0	0
KATNA1	0.02	0.005	-10000	0	-10000	0	0
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	-0.041	0.049	-10000	0	-0.12	182	182
IQGAP1/CaM	0.03	0.011	0.11	6	-10000	0	6
DAB1	0.015	0.01	-10000	0	-10000	0	0
IQGAP1	0.022	0.01	0.12	6	-10000	0	6
PLA2G7	0.021	0.006	0.12	2	-10000	0	2
CALM1	0.02	0.005	-10000	0	-10000	0	0
DYNLT1	0.03	0.031	0.12	63	-10000	0	63
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	0.028	0.01	-10000	0	-10000	0	0
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0.021	0.002	-10000	0	-10000	0	0
CDK5R1	0.019	0.006	-10000	0	-10000	0	0
LIS1/Poliovirus Protein 3A	-0.01	0.002	-10000	0	-10000	0	0
CDK5R2	0.014	0.01	-10000	0	-10000	0	0
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.039	0.089	-10000	0	-0.15	246	246
YWHAE	0.021	0.002	-10000	0	-10000	0	0
NDEL1/14-3-3 E	-0.041	0.15	0.28	72	-0.26	100	172
MAP1B	0.004	0.001	-10000	0	-10000	0	0
RAC1	0.007	0.004	-10000	0	-10000	0	0
p35/CDK5	-0.044	0.061	0.17	10	-0.21	30	40
RELN	0.011	0.011	-10000	0	-10000	0	0
PAFAH/LIS1	0.018	0.015	0.094	2	-0.13	5	7
LIS1/CLIP170	0.019	0.005	-10000	0	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.065	0.085	0.12	6	-0.23	95	101
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.074	0.12	-10000	0	-0.32	92	92
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	-0.071	0.1	0.16	7	-0.23	154	161
LIS1/IQGAP1	0.02	0.009	0.094	6	-10000	0	6
RHOA	0.007	0.003	-10000	0	-10000	0	0
PAFAH1B1	-0.012	0.003	-10000	0	-10000	0	0
PAFAH1B3	0.019	0.007	-10000	0	-10000	0	0
PAFAH1B2	0.021	0.003	-10000	0	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0.018	0.014	-10000	0	-0.11	3	3
NDEL1/Katanin 60/Dynein heavy chain	-0.03	0.14	0.28	64	-0.26	99	163
LRP8	0.019	0.007	-10000	0	-10000	0	0
NDEL1/Katanin 60	-0.043	0.14	0.28	67	-0.26	100	167
P39/CDK5	-0.059	0.071	0.17	7	-0.21	73	80
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.017	0.007	-10000	0	-10000	0	0
CDK5	-0.038	0.05	0.17	6	-0.12	146	152
PPP2R5D	0.021	0.002	-10000	0	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.017	0.004	-10000	0	-10000	0	0
CSNK2A1	0.02	0.004	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.03	0.079	-10000	0	-0.13	237	237
RELN/VLDLR	-0.01	0.072	-10000	0	-0.12	190	190
CDC42	0.007	0.004	-10000	0	-10000	0	0

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.006	0.11	-10000	0	-0.45	35	35
IHH	0.018	0.034	0.11	7	-0.12	35	42
SHH Np/Cholesterol/GAS1	0.01	0.043	0.09	53	-0.12	50	103
LRPAP1	0.021	0.003	-10000	0	-10000	0	0
dorsoventral neural tube patterning	-0.01	0.042	0.12	50	-0.089	53	103
SMO/beta Arrestin2	0.012	0.072	-10000	0	-0.28	26	26
SMO	0	0.065	-10000	0	-0.29	27	27
AKT1	0.004	0.076	-10000	0	-0.4	16	16
ARRB2	0.021	0.002	-10000	0	-10000	0	0
BOC	0.027	0.025	0.12	42	-10000	0	42
ADRBK1	0.021	0.003	-10000	0	-10000	0	0
heart looping	0	0.064	-10000	0	-0.28	27	27
STIL	0.004	0.087	0.17	101	-0.22	29	130
DHH N/PTCH2	0.029	0.02	-10000	0	-0.16	2	2
DHH N/PTCH1	0.017	0.065	-10000	0	-0.25	34	34
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
DHH	0.023	0.018	0.12	19	-10000	0	19
PTHLH	-0.023	0.17	-10000	0	-0.72	35	35
determination of left/right symmetry	0	0.064	-10000	0	-0.28	27	27
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
skeletal system development	-0.023	0.16	-10000	0	-0.71	35	35
IHH N/Hhip	-0.005	0.079	0.12	1	-0.18	106	107
DHH N/Hhip	0.002	0.07	0.11	15	-0.16	105	120
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	0	0.064	-10000	0	-0.28	27	27
pancreas development	0.017	0.009	0.12	1	-10000	0	1
HHAT	0.021	0.002	-10000	0	-10000	0	0
PI3K	0.03	0.006	-10000	0	-10000	0	0
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	0.037	0.038	0.12	107	-10000	0	107
somite specification	0	0.064	-10000	0	-0.28	27	27
SHH Np/Cholesterol/PTCH1	-0.005	0.059	-10000	0	-0.24	29	29
SHH Np/Cholesterol/PTCH2	0.002	0.037	-10000	0	-0.12	53	53
SHH Np/Cholesterol/Megalin	-0.003	0.05	0.086	16	-0.12	92	108
SHH	-0.009	0.008	0.051	4	-10000	0	4
catabolic process	0.004	0.068	-10000	0	-0.28	34	34
SMO/Vitamin D3	-0.004	0.071	0.24	6	-0.27	27	33
SHH Np/Cholesterol/Hhip	-0.012	0.055	-10000	0	-0.13	119	119
LRP2	0.022	0.018	0.12	18	-10000	0	18
receptor-mediated endocytosis	-0.016	0.074	0.2	2	-0.28	32	34
SHH Np/Cholesterol/BOC	0.007	0.04	0.086	32	-0.12	52	84
SHH Np/Cholesterol/CDO	0.004	0.036	0.086	3	-0.12	51	54
mesenchymal cell differentiation	0.012	0.055	0.12	119	-10000	0	119
mol:Vitamin D3	0.022	0.092	0.18	108	-0.24	29	137
IHH N/PTCH2	0.026	0.024	-10000	0	-0.22	2	2
CDON	0.022	0.012	0.12	8	-10000	0	8
IHH N/PTCH1	0.012	0.071	-10000	0	-0.28	34	34
Megalin/LRPAP1	0.014	0.058	0.11	18	-0.16	66	84
PTCH2	0.019	0.007	-10000	0	-10000	0	0
SHH Np/Cholesterol	-0.003	0.033	-10000	0	-0.11	52	52
PTCH1	0.004	0.068	-10000	0	-0.28	34	34
HHIP	0.017	0.009	0.12	1	-10000	0	1

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.027	0.011	-10000	0	-10000	0	0
Necdin/E2F1	0.025	0.032	-10000	0	-0.16	18	18
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.05	0.053	0.18	1	-0.12	41	42
NGF (dimer)/p75(NTR)/BEX1	0.031	0.055	-10000	0	-0.13	53	53
NT-4/5 (dimer)/p75(NTR)	0.036	0.031	0.11	94	-10000	0	94
IKBKB	0.021	0.003	-10000	0	-10000	0	0
AKT1	-0.013	0.043	0.18	18	-10000	0	18
IKBKG	0.021	0.002	-10000	0	-10000	0	0
BDNF	0.01	0.011	-10000	0	-10000	0	0
MGDIs/NGR/p75(NTR)/LINGO1	0.003	0.087	-10000	0	-0.15	150	150
FURIN	0.021	0.003	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.044	0.089	-10000	0	-0.13	335	335
LINGO1	0.02	0.005	-10000	0	-10000	0	0
Sortilin/TRAF6/NRIF	0.021	0.015	-10000	0	-10000	0	0
proBDNF (dimer)	0.01	0.01	-10000	0	-10000	0	0
NTRK1	0.026	0.023	0.12	35	-10000	0	35
RTN4R	0.016	0.009	-10000	0	-10000	0	0
neuron apoptosis	-0.077	0.12	0.28	6	-0.37	63	69
IRAK1	0.021	0.002	-10000	0	-10000	0	0
SHC1	-0.013	0.036	0.072	15	-0.13	40	55
ARHGDIA	0.021	0.003	-10000	0	-10000	0	0
RhoA/GTP	0.015	0.002	-10000	0	-10000	0	0
Gamma Secretase	0.053	0.023	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.043	0.052	0.18	1	-0.12	41	42
MAGEH1	0.021	0.003	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	0.037	0.06	0.18	1	-0.13	60	61
Mammalian IAPs/DIABLO	0.051	0.028	-10000	0	-0.12	13	13
proNGF (dimer)	0.017	0.009	0.12	1	-10000	0	1
MAGED1	0.021	0	-10000	0	-10000	0	0
APP	0.021	0.003	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.019	0.02	0.12	22	-10000	0	22
ZNF274	0.018	0.007	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	0.018	0.035	-10000	0	-0.11	39	39
NGF	0.017	0.009	0.12	1	-10000	0	1
cell cycle arrest	-0.017	0.043	0.27	9	-10000	0	9
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.011	0.045	-10000	0	-0.16	35	35
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.045	0.031	0.18	4	-10000	0	4
NCSTN	0.021	0.002	-10000	0	-10000	0	0
mol:GTP	0.033	0.05	0.18	1	-0.13	41	42
PSENEN	0.019	0.006	-10000	0	-10000	0	0
mol:ceramide	-0.016	0.029	0.045	1	-0.12	37	38
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.026	0.076	-10000	0	-0.18	72	72
p75(NTR)/beta APP	0.04	0.026	-10000	0	-10000	0	0
BEX1	0.021	0.003	-10000	0	-10000	0	0
mol:GDP	-0.012	0.032	0.058	1	-0.13	41	42
NGF (dimer)	0.05	0.059	0.18	1	-0.12	41	42
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.013	0.086	-10000	0	-0.14	149	149
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
RAC1/GTP	0.025	0.039	0.16	1	-0.11	32	33
MYD88	0.027	0.024	0.12	38	-10000	0	38
CHUK	0.019	0.006	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	0.034	0.051	0.18	1	-0.13	41	42
RHOB	0.021	0.002	-10000	0	-10000	0	0
RHOA	0.021	0.003	-10000	0	-10000	0	0
MAGE-G1/E2F1	0.03	0.011	-10000	0	-10000	0	0
NT3 (dimer)	0.019	0.011	0.12	6	-10000	0	6
TP53	-0.05	0.074	0.22	19	-10000	0	19
PRDM4	-0.017	0.03	-10000	0	-0.12	40	40
BDNF (dimer)	-0.08	0.1	-10000	0	-0.14	457	457
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
SORT1	0.019	0.007	-10000	0	-10000	0	0
activation of caspase activity	0.045	0.05	0.17	1	-0.12	41	42
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.043	0.052	0.18	1	-0.12	41	42
RHOC	0.022	0.021	0.12	23	-10000	0	23
XIAP	0.021	0.001	-10000	0	-10000	0	0
MAPK10	-0.033	0.093	0.19	51	-0.23	25	76
DIABLO	0.021	0.002	-10000	0	-10000	0	0
SMPD2	-0.016	0.029	0.045	1	-0.12	37	38
APH1B	0.021	0.003	-10000	0	-10000	0	0
APH1A	0.021	0.002	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	0.034	0.051	0.18	1	-0.13	41	42
PSEN1	0.02	0.004	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.028	0.01	0.11	1	-10000	0	1
NT3 (dimer)/p75(NTR)	0.037	0.027	0.18	3	-10000	0	3
MAPK8	-0.041	0.08	0.23	16	-0.22	28	44
MAPK9	-0.033	0.091	0.19	51	-0.22	24	75
APAF1	0.021	0.002	-10000	0	-10000	0	0
NTF3	0.019	0.011	0.12	6	-10000	0	6
NTF4	0.019	0.021	0.12	22	-10000	0	22
NDN	0.02	0.005	-10000	0	-10000	0	0
RAC1/GDP	0.013	0.006	-10000	0	-10000	0	0
RhoA-B-C/GDP	0.044	0.049	0.15	7	-0.11	40	47
p75 CTF/Sortilin/TRAF6/NRIF	0.044	0.022	-10000	0	-10000	0	0
RhoA-B-C/GTP	0.033	0.05	0.17	1	-0.13	41	42
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.028	0.088	-10000	0	-0.11	328	328
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.034	0.089	-10000	0	-0.12	334	334
PRKACB	0.018	0.007	-10000	0	-10000	0	0
proBDNF (dimer)/p75 ECD	-0.067	0.093	-10000	0	-0.16	340	340
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.023	0.017	0.12	16	-10000	0	16
BIRC2	0.021	0.003	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.015	0.049	0.16	12	-0.15	38	50
BAD	-0.036	0.093	0.26	25	-0.23	26	51
RIPK2	0.02	0.007	0.12	2	-10000	0	2
NGFR	0.034	0.035	0.12	84	-10000	0	84
CYCS	-0.014	0.039	0.25	7	-10000	0	7
ADAM17	0.021	0.002	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.042	0.051	0.18	1	-0.12	38	39
BCL2L11	-0.036	0.091	0.25	24	-0.23	26	50
BDNF (dimer)/p75(NTR)	-0.06	0.099	0.11	44	-0.16	339	383
PI3K	0.043	0.051	0.18	1	-0.12	39	40
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.043	0.051	0.18	1	-0.12	41	42
NDNL2	0.021	0.003	-10000	0	-10000	0	0
YWHAE	0.021	0.002	-10000	0	-10000	0	0
PRKCI	0.021	0.003	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	0.024	0.054	0.18	1	-0.16	41	42
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.044	0.051	0.18	1	-0.12	41	42
TRAF6	0.021	0.003	-10000	0	-10000	0	0
RAC1	0.018	0.008	-10000	0	-10000	0	0
PRKCZ	0.016	0.009	-10000	0	-10000	0	0
PLG	0.016	0.008	0.12	3	-10000	0	3
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.071	0.075	0.09	5	-0.14	342	347
SQSTM1	0.021	0.003	-10000	0	-10000	0	0
NGFRAP1	0.021	0.001	-10000	0	-10000	0	0
CASP3	-0.034	0.089	0.24	25	-0.22	27	52
E2F1	0.021	0.011	0.12	7	-10000	0	7
CASP9	0.019	0.008	0.12	1	-10000	0	1
IKK complex	-0.004	0.095	-10000	0	-0.22	34	34
NGF (dimer)/TRKA	0.02	0.05	0.18	1	-0.16	41	42
MMP7	0.057	0.051	0.12	238	-10000	0	238
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.046	0.053	0.18	1	-0.11	40	41
MMP3	0.012	0.012	0.12	3	-10000	0	3
APAF-1/Caspase 9	-0.028	0.029	-10000	0	-0.19	4	4

×

amb2 Integrin 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
alphaM/beta2 Integrin/proMMP-2	0.037	0.058	0.2	6	-0.1	19	25
alphaM/beta2 Integrin/GPIbA	0.022	0.048	0.19	1	-0.1	24	25
alphaM/beta2 Integrin/proMMP-9	0.04	0.062	0.19	6	-0.099	21	27
PLAUR	0.026	0.028	0.12	46	-10000	0	46
HMGB1	0.007	0.029	-10000	0	-0.053	125	125
alphaM/beta2 Integrin/Talin	0.021	0.047	0.19	1	-0.092	27	28
AGER	0.015	0.043	0.12	52	-0.053	124	176
RAP1A	0.019	0.007	-10000	0	-10000	0	0
SELPLG	0.021	0.005	0.12	1	-10000	0	1
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	0.013	0.1	0.2	2	-0.19	128	130
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	0.05	0.048	0.12	193	-10000	0	193
CYR61	0.022	0.021	0.12	23	-10000	0	23
TLN1	0.02	0.005	-10000	0	-10000	0	0
Rap1/GTP	-0.005	0.074	-10000	0	-0.27	10	10
RHOA	0.021	0.003	-10000	0	-10000	0	0
P-selectin oligomer	0.022	0.015	0.12	14	-10000	0	14
MYH2	-0.018	0.078	0.17	5	-0.29	10	15
MST1R	0.021	0.005	0.12	1	-10000	0	1
leukocyte activation during inflammatory response	-0.006	0.072	0.16	1	-0.12	142	143
APOB	0.02	0.01	0.12	4	-10000	0	4
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	0.044	0.043	0.12	145	-10000	0	145
JAM3	0.02	0.004	-10000	0	-10000	0	0
GP1BA	0.021	0.005	0.12	1	-10000	0	1
alphaM/beta2 Integrin/CTGF	0.023	0.049	0.19	1	-0.097	23	24
alphaM/beta2 Integrin	-0.017	0.075	0.12	2	-0.32	9	11
JAM3 homodimer	0.02	0.004	-10000	0	-10000	0	0
ICAM2	0.021	0.003	-10000	0	-10000	0	0
ICAM1	0.027	0.025	0.12	40	-10000	0	40
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.016	0.075	-10000	0	-0.32	9	9
cell adhesion	0.021	0.048	0.18	1	-0.1	24	25
NFKB1	-0.062	0.13	0.19	13	-0.32	127	140
THY1	0.02	0.004	-10000	0	-10000	0	0
RhoA/GDP	0.015	0.002	-10000	0	-10000	0	0
Lipoprotein(a)	-0.007	0.065	0.096	3	-0.13	137	140
alphaM/beta2 Integrin/LRP/tPA	0.034	0.054	0.19	1	-0.097	18	19
IL6	-0.088	0.19	0.18	1	-0.49	114	115
ITGB2	0.008	0.033	0.13	9	-0.053	130	139
elevation of cytosolic calcium ion concentration	0.041	0.067	0.19	44	-0.1	12	56
alphaM/beta2 Integrin/JAM2/JAM3	0.031	0.05	0.19	1	-0.098	17	18
JAM2	0.021	0.009	0.12	4	-10000	0	4
alphaM/beta2 Integrin/ICAM1	0.049	0.058	0.2	5	-0.13	5	10
alphaM/beta2 Integrin/uPA/Plg	0.038	0.062	0.19	7	-0.099	16	23
RhoA/GTP	-0.015	0.081	-10000	0	-0.3	11	11
positive regulation of phagocytosis	-0.007	0.066	0.16	6	-0.26	8	14
Ron/MSP	0.039	0.027	-10000	0	-0.16	2	2
alphaM/beta2 Integrin/uPAR/uPA	0.042	0.069	0.19	44	-0.1	12	56
alphaM/beta2 Integrin/uPAR	0.024	0.052	0.21	3	-0.095	21	24
PLAU	0.041	0.044	0.12	138	-10000	0	138
PLAT	0.029	0.028	0.12	52	-10000	0	52
actin filament polymerization	-0.016	0.077	0.17	5	-0.35	6	11
MST1	0.033	0.034	0.12	78	-10000	0	78
alphaM/beta2 Integrin/lipoprotein(a)	-0.004	0.075	0.18	1	-0.12	142	143
TNF	-0.076	0.16	0.2	3	-0.37	128	131
RAP1B	0.021	0.009	0.12	4	-10000	0	4
alphaM/beta2 Integrin/uPA	0.033	0.061	0.19	7	-0.1	21	28
fibrinolysis	0.036	0.06	0.19	7	-0.099	16	23
HCK	0.022	0.014	0.12	11	-10000	0	11
dendritic cell antigen processing and presentation	-0.016	0.075	-10000	0	-0.32	9	9
VTN	0.021	0.006	0.12	2	-10000	0	2
alphaM/beta2 Integrin/CYR61	0.022	0.05	0.19	2	-0.11	21	23
LPA	0.015	0.009	0.12	1	-10000	0	1
LRP1	0.02	0.004	-10000	0	-10000	0	0
cell migration	0.027	0.05	0.16	7	-0.096	17	24
FN1	0.036	0.036	0.12	94	-10000	0	94
alphaM/beta2 Integrin/Thy1	0.019	0.051	0.19	1	-0.12	30	31
MPO	0.015	0.01	-10000	0	-10000	0	0
KNG1	0.018	0.014	0.12	10	-10000	0	10
RAP1/GDP	0.025	0.012	0.096	4	-10000	0	4
ROCK1	-0.016	0.079	0.19	7	-0.27	12	19
ELA2	0	0	-10000	0	-10000	0	0
PLG	0.016	0.008	0.12	3	-10000	0	3
CTGF	0.023	0.018	0.12	20	-10000	0	20
alphaM/beta2 Integrin/Hck	0.022	0.05	0.19	7	-0.1	22	29
ITGAM	0.007	0.031	0.13	1	-0.054	130	131
alphaM/beta2 Integrin/P-Selectin/PSGL1	0.031	0.052	0.21	3	-0.098	18	21
HP	0.05	0.047	0.12	188	-10000	0	188
leukocyte adhesion	0.002	0.085	0.2	1	-0.16	115	116
SELP	0.022	0.015	0.12	14	-10000	0	14

×

Ras signaling in the CD4+ TCR pathway

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
ERK1-2/ELK1	-0.02	0.11	-10000	0	-0.43	12	12
MAP3K8	0.02	0.016	0.12	12	-0.019	6	18
FOS	-0.028	0.1	-10000	0	-0.44	12	12
PRKCA	0.02	0.006	-10000	0	-0.025	7	7
PTPN7	0.036	0.037	0.12	96	-0.031	7	103
HRAS	0.02	0.005	-10000	0	-10000	0	0
PRKCB	0.014	0.011	-10000	0	-0.025	7	7
NRAS	0.019	0.007	-10000	0	-10000	0	0
RAS family/GTP	0.033	0.017	-10000	0	-10000	0	0
MAPK3	-0.006	0.073	-10000	0	-0.49	6	6
MAP2K1	-0.065	0.14	-10000	0	-0.29	169	169
ELK1	0.021	0.006	-10000	0	-0.034	7	7
BRAF	-0.045	0.12	-10000	0	-0.28	121	121
mol:GTP	0	0	-10000	0	-0.004	7	7
MAPK1	-0.012	0.094	-10000	0	-0.5	14	14
RAF1	-0.074	0.14	-10000	0	-0.28	190	190
KRAS	0.02	0.004	-10000	0	-10000	0	0

×

EPO signaling pathway

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
BCL2L1	0.041	0.044	0.29	2	-10000	0	2
CRKL	0.022	0.073	0.16	134	-10000	0	134
mol:DAG	0.02	0.026	0.16	4	-10000	0	4
HRAS	0.02	0.083	0.2	68	-10000	0	68
MAPK8	-0.004	0.033	0.15	22	-10000	0	22
RAP1A	0.021	0.07	0.16	125	-10000	0	125
GAB1	0.022	0.073	0.16	135	-10000	0	135
MAPK14	0.001	0.043	0.16	41	-10000	0	41
EPO	0.026	0.031	0.13	50	-10000	0	50
PLCG1	0.02	0.026	0.17	4	-10000	0	4
EPOR/TRPC2/IP3 Receptors	0.025	0.008	0.079	2	-10000	0	2
RAPGEF1	0.021	0.003	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.028	0.053	0.15	5	-0.14	43	48
GAB1/SHC/GRB2/SOS1	0.054	0.048	0.18	23	-10000	0	23
EPO/EPOR (dimer)	0.032	0.027	0.11	46	-10000	0	46
IRS2	0.021	0.071	0.16	133	-10000	0	133
STAT1	0.023	0.028	0.18	4	-10000	0	4
STAT5B	0.022	0.027	0.17	4	-10000	0	4
cell proliferation	0.012	0.07	0.17	97	-10000	0	97
GAB1/SHIP/PIK3R1/SHP2/SHC	0.04	0.035	0.13	19	-10000	0	19
TEC	0.022	0.073	0.16	133	-10000	0	133
SOCS3	0.021	0.017	0.12	14	-10000	0	14
STAT1 (dimer)	0.023	0.028	0.18	4	-10000	0	4
JAK2	0.024	0.01	0.079	3	-10000	0	3
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.05	0.041	0.2	19	-10000	0	19
EPO/EPOR	0.032	0.027	0.11	46	-10000	0	46
LYN	0.021	0.008	0.12	3	-10000	0	3
TEC/VAV2	0.013	0.058	0.13	114	-10000	0	114
elevation of cytosolic calcium ion concentration	0.025	0.008	0.079	2	-10000	0	2
SHC1	0.023	0.016	0.12	16	-10000	0	16
EPO/EPOR (dimer)/LYN	0.041	0.029	0.14	5	-10000	0	5
mol:IP3	0.02	0.026	0.16	4	-10000	0	4
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.058	0.062	0.19	61	-10000	0	61
SH2B3	0.026	0.009	0.1	2	-10000	0	2
NFKB1	0.001	0.043	0.15	45	-10000	0	45
EPO/EPOR (dimer)/JAK2/SOCS3	0.001	0.043	-10000	0	-0.15	43	43
PTPN6	0.026	0.074	0.16	137	-10000	0	137
TEC/VAV2/GRB2	0.045	0.046	0.18	23	-10000	0	23
EPOR	0.025	0.008	0.08	2	-10000	0	2
INPP5D	0.021	0.009	0.12	5	-10000	0	5
mol:GDP	0.053	0.049	0.18	23	-10000	0	23
SOS1	0.021	0.001	-10000	0	-10000	0	0
PLCG2	0.022	0.009	0.12	5	-10000	0	5
CRKL/CBL/C3G	0.046	0.047	0.16	47	-10000	0	47
VAV2	0.022	0.073	0.16	134	-10000	0	134
CBL	0.023	0.074	0.16	136	-10000	0	136
SHC/Grb2/SOS1	0.028	0.021	-10000	0	-10000	0	0
STAT5A	0.022	0.027	0.17	4	-10000	0	4
GRB2	0.02	0.004	-10000	0	-10000	0	0
STAT5 (dimer)	0.032	0.032	0.2	4	-10000	0	4
LYN/PLCgamma2	0.031	0.013	0.15	5	-10000	0	5
PTPN11	0.021	0.003	-10000	0	-10000	0	0
BTK	0.026	0.075	0.16	140	-10000	0	140
BCL2	0.042	0.047	0.29	2	-10000	0	2

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.021	0.003	-10000	0	-10000	0	0
Syndecan-3/Src/Cortactin	0	0.11	-10000	0	-0.35	59	59
Syndecan-3/Neurocan	-0.016	0.12	-10000	0	-0.38	62	62
POMC	0.021	0.005	0.12	1	-10000	0	1
EGFR	0.053	0.054	0.12	235	-10000	0	235
Syndecan-3/EGFR	0.001	0.12	-10000	0	-0.36	61	61
AGRP	0.02	0.009	0.12	4	-10000	0	4
NCSTN	0.021	0.002	-10000	0	-10000	0	0
PSENEN	0.019	0.006	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
APH1B	0.021	0.003	-10000	0	-10000	0	0
APH1A	0.021	0.002	-10000	0	-10000	0	0
NCAN	0.02	0.007	0.12	2	-10000	0	2
long-term memory	-0.003	0.12	-10000	0	-0.36	61	61
Syndecan-3/IL8	-0.012	0.13	-10000	0	-0.4	62	62
PSEN1	0.02	0.004	-10000	0	-10000	0	0
Src/Cortactin	0.03	0.007	-10000	0	-10000	0	0
FYN	0.02	0.004	-10000	0	-10000	0	0
limb bud formation	-0.029	0.12	-10000	0	-0.39	62	62
MC4R	0.015	0.01	0.12	1	-10000	0	1
SRC	0.02	0.004	-10000	0	-10000	0	0
PTN	0.017	0.013	0.12	5	-10000	0	5
FGFR/FGF/Syndecan-3	-0.029	0.12	-10000	0	-0.39	62	62
neuron projection morphogenesis	0	0.12	-10000	0	-0.35	55	55
Syndecan-3/AgRP	-0.015	0.12	-10000	0	-0.38	62	62
Syndecan-3/AgRP/MC4R	-0.035	0.12	-10000	0	-0.38	62	62
Fyn/Cortactin	0.03	0.007	-10000	0	-10000	0	0
SDC3	-0.029	0.12	-10000	0	-0.39	62	62
GO:0007205	0	0	-10000	0	-10000	0	0
positive regulation of leukocyte migration	-0.012	0.12	-10000	0	-0.39	62	62
IL8	0.027	0.032	0.12	60	-10000	0	60
Syndecan-3/Fyn/Cortactin	-0.003	0.12	-10000	0	-0.37	61	61
Syndecan-3/CASK	-0.028	0.11	-10000	0	-0.37	62	62
alpha-MSH/MC4R	-0.019	0.082	-10000	0	-0.16	174	174
Gamma Secretase	0.053	0.023	-10000	0	-10000	0	0

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.023	0.042	-10000	0	-0.28	3	3
Syndecan-4/Syndesmos	0.022	0.1	-10000	0	-0.38	22	22
positive regulation of JNK cascade	0.031	0.1	-10000	0	-0.36	23	23
Syndecan-4/ADAM12	0.022	0.1	0.26	1	-0.38	23	24
CCL5	0.036	0.037	0.12	97	-10000	0	97
Rac1/GDP	0.013	0.006	-10000	0	-10000	0	0
DNM2	0.02	0.004	-10000	0	-10000	0	0
ITGA5	0.034	0.036	0.12	89	-10000	0	89
SDCBP	0.02	0.004	-10000	0	-10000	0	0
PLG	0.012	0.016	0.11	3	-0.04	44	47
ADAM12	0.032	0.036	0.12	85	-10000	0	85
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0.021	0.002	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.03	0.015	-10000	0	-0.056	1	1
Syndecan-4/Laminin alpha1	0.024	0.1	0.27	3	-0.39	23	26
Syndecan-4/CXCL12/CXCR4	0.033	0.1	-10000	0	-0.38	22	22
Syndecan-4/Laminin alpha3	0.017	0.1	-10000	0	-0.39	25	25
MDK	0.05	0.047	0.12	188	-10000	0	188
Syndecan-4/FZD7	0.028	0.11	0.26	4	-0.39	24	28
Syndecan-4/Midkine	0.04	0.11	0.26	9	-0.38	22	31
FZD7	0.032	0.033	0.12	73	-10000	0	73
Syndecan-4/FGFR1/FGF	0.03	0.098	-10000	0	-0.37	22	22
THBS1	0.024	0.02	0.12	24	-10000	0	24
integrin-mediated signaling pathway	0.058	0.11	0.26	9	-0.37	23	32
positive regulation of MAPKKK cascade	0.031	0.1	-10000	0	-0.36	23	23
Syndecan-4/TACI	0.019	0.1	-10000	0	-0.38	24	24
CXCR4	0.039	0.039	0.12	113	-10000	0	113
cell adhesion	0.016	0.032	0.2	15	-10000	0	15
Syndecan-4/Dynamin	0.018	0.099	-10000	0	-0.39	22	22
Syndecan-4/TSP1	0.022	0.1	0.26	1	-0.4	22	23
Syndecan-4/GIPC	0.018	0.099	-10000	0	-0.38	24	24
Syndecan-4/RANTES	0.03	0.11	-10000	0	-0.38	24	24
ITGB1	0.021	0.016	0.12	12	-10000	0	12
LAMA1	0.025	0.022	0.12	30	-10000	0	30
LAMA3	0.02	0.006	0.12	1	-10000	0	1
RAC1	0.018	0.008	-10000	0	-10000	0	0
PRKCA	0.009	0.14	0.83	17	-10000	0	17
Syndecan-4/alpha-Actinin	0.021	0.099	-10000	0	-0.38	22	22
TFPI	0.065	0.051	0.12	282	-10000	0	282
F2	0.018	0.016	0.1	5	-0.035	22	27
alpha5/beta1 Integrin	0.037	0.031	0.18	10	-10000	0	10
positive regulation of cell adhesion	0.011	0.099	0.24	1	-0.39	25	26
ACTN1	0.02	0.005	-10000	0	-10000	0	0
TNC	0.083	0.051	0.12	401	-10000	0	401
Syndecan-4/CXCL12	0.015	0.097	-10000	0	-0.38	22	22
FGF6	0.015	0.004	-10000	0	-10000	0	0
RHOA	0.021	0.003	-10000	0	-10000	0	0
CXCL12	0.02	0.01	0.12	4	-10000	0	4
TNFRSF13B	0.018	0.008	0.12	3	-10000	0	3
FGF2	0.021	0.005	0.12	1	-10000	0	1
FGFR1	0.021	0.003	-10000	0	-10000	0	0
Syndecan-4/PI-4-5-P2	0.002	0.091	-10000	0	-0.37	24	24
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.032	0.039	0.12	94	-0.041	35	129
cell migration	-0.017	0.009	-10000	0	-0.039	1	1
PRKCD	0.016	0.016	-10000	0	-0.039	43	43
vasculogenesis	0.022	0.1	0.26	1	-0.38	23	24
SDC4	0.007	0.094	-10000	0	-0.39	24	24
Syndecan-4/Tenascin C	0.059	0.12	0.26	9	-0.38	23	32
Syndecan-4/PI-4-5-P2/PKC alpha	-0.024	0.012	-10000	0	-0.045	1	1
Syndecan-4/Syntenin	0.021	0.099	-10000	0	-0.38	23	23
MMP9	0.047	0.05	0.12	192	-0.033	23	215
Rac1/GTP	0.016	0.033	0.2	15	-10000	0	15
cytoskeleton organization	0.021	0.097	-10000	0	-0.37	23	23
GIPC1	0.02	0.004	-10000	0	-10000	0	0
Syndecan-4/TFPI	0.048	0.12	0.26	9	-0.38	22	31

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	0.011	0.024	0.05	182	-10000	0	182
TP53	0.005	0.031	-10000	0	-0.16	20	20
Senescence	0.005	0.031	-10000	0	-0.15	21	21
Apoptosis	0.005	0.031	-10000	0	-0.15	21	21
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	-0.007	0.045	0.28	15	-10000	0	15
MDM4	0.02	0.005	-10000	0	-10000	0	0

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.031	0.033	0.12	72	-10000	0	72
HRAS	0.02	0.005	-10000	0	-10000	0	0
EGFR	0.053	0.054	0.12	235	-10000	0	235
AKT	0.04	0.11	0.22	125	-0.14	18	143
FOXO3	0.02	0.004	-10000	0	-10000	0	0
AKT1	0.02	0.004	-10000	0	-10000	0	0
FOXO1	0.02	0.004	-10000	0	-10000	0	0
AKT3	0.021	0.003	-10000	0	-10000	0	0
FOXO4	0.021	0.002	-10000	0	-10000	0	0
MET	0.009	0.011	0.12	1	-10000	0	1
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
PIK3CB	0.021	0.002	-10000	0	-10000	0	0
NRAS	0.019	0.007	-10000	0	-10000	0	0
PIK3CG	0.019	0.018	0.12	14	-10000	0	14
PIK3R3	0.019	0.006	-10000	0	-10000	0	0
PIK3R2	0.02	0.004	-10000	0	-10000	0	0
NF1	0.021	0.002	-10000	0	-10000	0	0
RAS	-0.007	0.052	0.11	10	-0.095	127	137
ERBB2	0.022	0.011	0.12	8	-10000	0	8
proliferation/survival/translation	-0.013	0.065	0.35	9	-0.21	13	22
PI3K	0.015	0.1	0.2	100	-0.11	83	183
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
KRAS	0.02	0.004	-10000	0	-10000	0	0
FOXO	0.055	0.09	0.2	136	-10000	0	136
AKT2	0.019	0.007	-10000	0	-10000	0	0
PTEN	0.018	0.007	-10000	0	-10000	0	0

×

EGFR-dependent Endothelin 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.02	0.005	-10000	0	-9999	0
EGFR	0.053	0.054	0.12	235	-9999	235
EGF/EGFR	0.053	0.043	0.14	33	-9999	33
EGF/EGFR dimer/SHC/GRB2/SOS1	0.066	0.05	0.18	5	-9999	5
mol:GTP	0	0	-10000	0	-9999	0
EDNRA	0.032	0.033	0.12	75	-9999	75
response to oxidative stress	0	0	-10000	0	-9999	0
EGF	0.024	0.019	0.12	22	-9999	22
EGF/EGFR dimer/SHC	0.057	0.046	0.18	7	-9999	7
mol:GDP	0.06	0.046	0.17	5	-9999	5
mol:Ca2+	0	0	-10000	0	-9999	0
EDN1	0.023	0.015	0.12	13	-9999	13
GRB2/SOS1	0.03	0.006	-10000	0	-9999	0
HRAS/GTP	0.039	0.031	-10000	0	-9999	0
SHC1	0.023	0.016	0.12	16	-9999	16
HRAS/GDP	0.052	0.042	-10000	0	-9999	0
FRAP1	-0.009	0.008	-10000	0	-9999	0
EGF/EGFR dimer	0.05	0.045	0.11	237	-9999	237
SOS1	0.021	0.001	-10000	0	-9999	0
GRB2	0.02	0.004	-10000	0	-9999	0
ETA receptor/Endothelin-1	0.04	0.027	0.11	86	-9999	86

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	-0.011	0.006	0.024	5	-10000	0	5
RAS family/GTP	0.003	0.08	0.22	1	-0.16	89	90
NFATC4	-0.034	0.052	0.2	8	-0.18	4	12
ERBB2IP	0.022	0.007	0.13	2	-10000	0	2
HSP90 (dimer)	0.02	0.004	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.035	0.058	0.15	2	-0.15	118	120
JUN	0	0.051	0.18	5	-10000	0	5
HRAS	0.02	0.005	-10000	0	-10000	0	0
DOCK7	-0.039	0.055	0.13	11	-0.15	103	114
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.006	0.067	-10000	0	-0.13	126	126
AKT1	-0.007	0.005	0.027	2	-10000	0	2
BAD	-0.01	0.004	0.018	2	-10000	0	2
MAPK10	-0.018	0.048	0.11	14	-0.13	2	16
mol:GTP	0	0	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.036	0.062	0.16	2	-0.16	118	120
RAF1	-0.015	0.08	0.22	22	-0.28	5	27
ErbB2/ErbB3/neuregulin 2	0.015	0.032	0.2	1	-0.13	13	14
STAT3	0.023	0.037	-10000	0	-0.89	1	1
cell migration	-0.016	0.052	0.22	8	-0.16	1	9
mol:PI-3-4-5-P3	-0.001	0.001	-10000	0	-10000	0	0
cell proliferation	0.013	0.11	0.43	3	-0.59	4	7
FOS	0.012	0.091	0.34	6	-0.39	11	17
NRAS	0.019	0.007	-10000	0	-10000	0	0
mol:Ca2+	-0.035	0.058	0.15	2	-0.15	118	120
MAPK3	0.011	0.097	0.41	3	-0.53	4	7
MAPK1	0.008	0.1	0.41	3	-0.53	5	8
JAK2	-0.039	0.052	0.12	11	-0.15	99	110
NF2	0.003	0.028	-10000	0	-0.69	1	1
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.022	0.075	0.15	2	-0.18	120	122
NRG1	0.016	0.009	-10000	0	-10000	0	0
GRB2/SOS1	0.03	0.006	-10000	0	-10000	0	0
MAPK8	-0.032	0.082	-10000	0	-0.21	108	108
MAPK9	-0.018	0.047	0.11	10	-0.13	2	12
ERBB2	-0.019	0.009	-10000	0	-10000	0	0
ERBB3	0.02	0.009	0.12	4	-10000	0	4
SHC1	0.023	0.016	0.12	16	-10000	0	16
RAC1	0.018	0.008	-10000	0	-10000	0	0
apoptosis	0.006	0.009	-10000	0	-0.22	1	1
STAT3 (dimer)	0.023	0.036	-10000	0	-0.87	1	1
RNF41	-0.014	0.006	0.018	1	-10000	0	1
FRAP1	-0.006	0.003	0.013	5	-10000	0	5
RAC1-CDC42/GTP	-0.033	0.039	-10000	0	-0.12	100	100
ErbB2/ErbB2/HSP90 (dimer)	-0.018	0.011	-10000	0	-10000	0	0
CHRNA1	0.021	0.088	0.34	5	-0.51	4	9
myelination	-0.034	0.056	0.28	6	-0.18	4	10
PPP3CB	-0.039	0.049	0.12	7	-0.14	98	105
KRAS	0.02	0.005	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.006	0.074	-10000	0	-0.16	106	106
NRG2	0.021	0.003	-10000	0	-10000	0	0
mol:GDP	-0.022	0.075	0.15	2	-0.17	120	122
SOS1	0.021	0.001	-10000	0	-10000	0	0
MAP2K2	-0.012	0.079	0.2	30	-0.24	6	36
SRC	0.02	0.004	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.001	-10000	0	-10000	0	0
PTPN11	-0.042	0.054	0.12	12	-0.15	105	117
MAP2K1	-0.005	0.12	0.61	1	-0.57	11	12
heart morphogenesis	-0.035	0.058	0.15	2	-0.15	118	120
RAS family/GDP	0.002	0.082	0.22	1	-0.16	90	91
GRB2	0.02	0.004	-10000	0	-10000	0	0
PRKACA	0.008	0.03	-10000	0	-0.73	1	1
CHRNE	0.002	0.013	0.064	6	-10000	0	6
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
activation of caspase activity	0.007	0.005	-10000	0	-0.027	2	2
nervous system development	-0.035	0.058	0.15	2	-0.15	118	120
CDC42	0.019	0.006	-10000	0	-10000	0	0

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.019	0.014	-10000	0	-0.088	11	11
SVIL	0.018	0.018	0.12	6	-0.08	12	18
ZNF318	0.022	0.022	0.17	12	-10000	0	12
JMJD2C	0.002	0.007	0.041	1	-10000	0	1
T-DHT/AR/Ubc9	0.057	0.047	0.12	44	-0.076	25	69
CARM1	0.019	0.007	-10000	0	-0.026	12	12
PRDX1	0.019	0.007	-10000	0	-10000	0	0
PELP1	0.021	0.004	-10000	0	-10000	0	0
CTNNB1	0.019	0.012	-10000	0	-0.068	12	12
AKT1	0.021	0.008	0.066	12	-0.017	1	13
PTK2B	0.019	0.011	-10000	0	-0.061	11	11
MED1	0.022	0.007	0.072	11	-10000	0	11
MAK	0.033	0.039	0.13	80	-10000	0	80
response to oxidative stress	0	0.002	-10000	0	-10000	0	0
HIP1	0.017	0.019	0.12	8	-0.08	11	19
GSN	0.019	0.015	-10000	0	-0.09	12	12
NCOA2	0.019	0.007	-10000	0	-0.026	11	11
NCOA6	0.019	0.014	-10000	0	-0.076	12	12
DNA-PK	0.042	0.02	0.18	10	-10000	0	10
NCOA4	0.018	0.008	-10000	0	-0.021	12	12
PIAS3	0.018	0.013	-10000	0	-0.068	11	11
cell proliferation	0.017	0.058	0.23	1	-0.39	9	10
XRCC5	0.021	0.005	0.063	1	-10000	0	1
UBE3A	0.019	0.018	-10000	0	-0.11	11	11
T-DHT/AR/SNURF	0.051	0.056	0.12	42	-0.097	45	87
FHL2	-0.023	0.18	-10000	0	-0.69	44	44
RANBP9	0.019	0.013	-10000	0	-0.076	12	12
JMJD1A	0.005	0.011	0.039	56	-10000	0	56
CDK6	0.024	0.028	0.12	43	-10000	0	43
TGFB1I1	0.049	0.049	0.12	186	-0.078	11	197
T-DHT/AR/CyclinD1	0.06	0.049	0.13	52	-0.075	21	73
XRCC6	0.021	0.006	0.063	1	-10000	0	1
T-DHT/AR	0.052	0.065	0.15	36	-0.14	42	78
CTDSP1	0.02	0.009	0.12	1	-0.037	12	13
CTDSP2	0.02	0.016	0.12	11	-10000	0	11
BRCA1	0.022	0.022	0.12	18	-0.08	12	30
TCF4	0.021	0.013	0.1	12	-0.018	22	34
CDKN2A	0.045	0.05	0.12	190	-0.017	2	192
SRF	0.013	0.041	-10000	0	-0.14	44	44
NKX3-1	0.005	0.021	0.06	4	-0.086	1	5
KLK3	-0.015	0.17	-10000	0	-1.2	12	12
TMF1	0.02	0.007	-10000	0	-0.026	12	12
HNRNPA1	0.021	0.01	0.079	12	-0.017	6	18
AOF2	-0.001	0.009	-10000	0	-0.064	12	12
APPL1	-0.01	0.016	0.1	12	-10000	0	12
T-DHT/AR/Caspase 8	0.061	0.05	0.13	56	-0.076	24	80
AR	0.07	0.057	0.12	329	-0.063	25	354
UBA3	0.02	0.008	-10000	0	-0.037	12	12
PATZ1	0.021	0.009	0.076	12	-0.017	6	18
PAWR	0.022	0.017	0.12	15	-0.026	11	26
PRKDC	0.021	0.005	0.054	9	-10000	0	9
PA2G4	0.02	0.011	0.089	11	-10000	0	11
UBE2I	0.021	0.002	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	0.055	0.044	0.11	45	-0.066	24	69
RPS6KA3	0.019	0.015	-10000	0	-0.09	12	12
T-DHT/AR/ARA70	0.05	0.049	0.12	35	-0.076	25	60
LATS2	0.021	0.01	0.085	11	-0.016	6	17
T-DHT/AR/PRX1	0.053	0.047	0.12	49	-0.068	14	63
Cyclin D3/CDK11 p58	0.016	0.002	-10000	0	-10000	0	0
VAV3	0.018	0.02	0.12	11	-0.068	11	22
KLK2	0.005	0.047	-10000	0	-0.32	10	10
CASP8	0.025	0.019	0.12	23	-10000	0	23
T-DHT/AR/TIF2/CARM1	0.059	0.055	0.13	33	-0.12	12	45
TMPRSS2	0.016	0.032	-10000	0	-10000	0	0
CCND1	0.026	0.027	0.12	43	-0.047	10	53
PIAS1	0.019	0.018	-10000	0	-0.11	11	11
mol:T-DHT	-0.002	0.014	-10000	0	-0.052	45	45
CDC2L1	0	0.001	-10000	0	-10000	0	0
PIAS4	0.018	0.025	-10000	0	-0.16	12	12
T-DHT/AR/CDK6	0.047	0.053	0.13	48	-0.075	24	72
CMTM2	0.021	0.006	0.12	2	-10000	0	2
SNURF	0.02	0.004	-10000	0	-10000	0	0
ZMIZ1	0.015	0.022	-10000	0	-0.064	42	42
CCND3	0.021	0.002	-10000	0	-10000	0	0
TGIF1	0.038	0.04	0.12	122	-0.017	4	126
FKBP4	0.019	0.013	-10000	0	-0.075	11	11

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.015	0.002	-10000	0	-10000	0	0
PRKCZ	0.016	0.009	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.02	0.005	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	0.012	0.049	-10000	0	-0.22	10	10
IRAK/TOLLIP	0.021	0.005	-10000	0	-10000	0	0
IKBKB	0.021	0.003	-10000	0	-10000	0	0
IKBKG	0.021	0.002	-10000	0	-10000	0	0
IL1 alpha/IL1R2	0.049	0.056	0.11	227	-0.15	28	255
IL1A	0.02	0.007	0.12	2	-10000	0	2
IL1B	0	0.025	0.051	114	-0.14	1	115
IRAK/TRAF6/p62/Atypical PKCs	0.026	0.052	0.16	2	-0.11	70	72
IL1R2	0.058	0.05	0.12	238	-10000	0	238
IL1R1	0.025	0.019	0.12	24	-10000	0	24
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0	0.052	-10000	0	-0.28	8	8
TOLLIP	0.02	0.005	-10000	0	-10000	0	0
TICAM2	0.021	0.002	-10000	0	-10000	0	0
MAP3K3	0.021	0.003	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.014	0.003	-10000	0	-10000	0	0
IKK complex/ELKS	-0.001	0.061	-10000	0	-0.27	6	6
JUN	-0.014	0.014	0.15	3	-10000	0	3
MAP3K7	0.02	0.004	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.046	0.063	0.2	3	-0.12	69	72
IL1 alpha/IL1R1/IL1RAP/MYD88	0.058	0.049	0.19	21	-0.12	27	48
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.064	0.05	0.19	22	-0.12	27	49
IL1 beta fragment/IL1R1/IL1RAP	0.03	0.061	0.14	47	-0.12	70	117
NFKB1	0.021	0.002	-10000	0	-10000	0	0
MAPK8	-0.013	0.018	0.16	6	-10000	0	6
IRAK1	-0.01	0.001	-10000	0	-10000	0	0
IL1RN/IL1R1	0.021	0.055	0.18	4	-0.16	52	56
IRAK4	0.021	0.007	0.12	2	-10000	0	2
PRKCI	0.021	0.003	-10000	0	-10000	0	0
TRAF6	0.021	0.003	-10000	0	-10000	0	0
PI3K	0.03	0.006	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.011	0.048	-10000	0	-0.19	12	12
CHUK	0.019	0.006	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.03	0.061	0.14	47	-0.12	70	117
IL1 beta/IL1R2	0.044	0.077	0.17	74	-0.13	71	145
IRAK/TRAF6/TAK1/TAB1/TAB2	0.027	0.007	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.031	0.053	0.13	3	-0.12	60	63
IRAK3	0.024	0.019	0.12	23	-10000	0	23
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.045	0.064	0.2	5	-0.12	70	75
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.015	0.042	-10000	0	-0.16	28	28
IL1 alpha/IL1R1/IL1RAP	0.044	0.045	0.18	3	-0.13	28	31
RELA	0.021	0.003	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.021	0.003	-10000	0	-10000	0	0
MYD88	0.027	0.024	0.12	38	-10000	0	38
IRAK/TRAF6/MEKK3	0.032	0.009	-10000	0	-10000	0	0
IL1RAP	0.031	0.032	0.12	68	-10000	0	68
UBE2N	0.021	0.002	-10000	0	-10000	0	0
IRAK/TRAF6	-0.019	0.046	0.068	46	-10000	0	46
CASP1	0.038	0.039	0.12	112	-10000	0	112
IL1RN/IL1R2	0.044	0.07	0.18	12	-0.16	52	64
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.043	0.067	0.16	66	-0.12	69	135
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.012	0.051	-10000	0	-0.27	9	9
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
IL1RN	0.021	0.016	0.12	13	-10000	0	13
TRAF6/TAK1/TAB1/TAB2	0.029	0.008	-10000	0	-10000	0	0
MAP2K6	-0.01	0.022	0.17	9	-10000	0	9

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.031	0.034	0.12	73	-0.047	4	77
PDGF/PDGFRA/CRKL	0.036	0.027	0.11	69	-0.14	1	70
positive regulation of JUN kinase activity	0.054	0.029	-10000	0	-0.11	1	1
CRKL	0.021	0.005	0.12	1	-10000	0	1
PDGF/PDGFRA/Caveolin-3	0.035	0.027	0.11	40	-0.14	1	41
AP1	-0.006	0.075	0.26	2	-0.58	7	9
mol:IP3	-0.005	0.021	0.052	69	-0.066	4	73
PLCG1	-0.005	0.021	0.052	69	-0.066	4	73
PDGF/PDGFRA/alphaV Integrin	0.037	0.026	0.1	68	-0.14	1	69
RAPGEF1	0.021	0.003	-10000	0	-10000	0	0
CRK	0.021	0.002	-10000	0	-10000	0	0
mol:Ca2+	-0.005	0.021	0.052	69	-0.066	4	73
CAV3	0.02	0.014	0.12	11	-10000	0	11
CAV1	0.028	0.035	0.12	73	-10000	0	73
SHC/Grb2/SOS1	0.055	0.03	-10000	0	-0.11	1	1
PDGF/PDGFRA/Shf	0.036	0.027	0.1	68	-0.14	1	69
FOS	-0.017	0.063	0.21	1	-0.58	7	8
JUN	-0.014	0.014	-10000	0	-10000	0	0
oligodendrocyte development	0.036	0.026	0.1	68	-0.14	1	69
GRB2	0.02	0.004	-10000	0	-10000	0	0
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
mol:DAG	-0.005	0.021	0.052	69	-0.066	4	73
PDGF/PDGFRA	0.031	0.034	0.12	73	-0.047	4	77
actin cytoskeleton reorganization	0.035	0.027	0.1	68	-0.12	1	69
SRF	-0.013	0.005	-10000	0	-10000	0	0
SHC1	0.023	0.016	0.12	16	-10000	0	16
PI3K	0.045	0.027	-10000	0	-0.12	1	1
PDGF/PDGFRA/Crk/C3G	0.045	0.027	-10000	0	-0.12	1	1
JAK1	-0.005	0.018	0.049	53	-10000	0	53
ELK1/SRF	-0.003	0.043	0.14	47	-0.12	1	48
SHB	0.02	0.004	-10000	0	-10000	0	0
SHF	0.021	0.003	-10000	0	-10000	0	0
CSNK2A1	0.018	0.013	-10000	0	-0.033	2	2
GO:0007205	-0.003	0.015	-10000	0	-10000	0	0
SOS1	0.021	0.001	-10000	0	-10000	0	0
Ras protein signal transduction	0.054	0.029	-10000	0	-0.11	1	1
PDGF/PDGFRA/SHB	0.035	0.027	0.1	68	-0.12	1	69
PDGF/PDGFRA/Caveolin-1	0.037	0.036	0.11	123	-10000	0	123
ITGAV	0.021	0.001	-10000	0	-10000	0	0
ELK1	-0.008	0.013	0.059	1	-0.1	3	4
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
PDGF/PDGFRA/Crk	0.036	0.027	0.11	1	-0.14	1	2
JAK-STAT cascade	-0.005	0.018	0.049	53	-10000	0	53
cell proliferation	0.036	0.027	0.1	68	-0.14	1	69

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.02	0.004	-10000	0	-10000	0	0
NFATC1	-0.013	0.078	0.24	1	-0.31	13	14
NFATC2	-0.025	0.072	-10000	0	-0.22	52	52
NFATC3	-0.016	0.081	-10000	0	-0.25	71	71
YWHAE	0.021	0.002	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.16	0.15	0.16	1	-0.34	241	242
Exportin 1/Ran/NUP214	0.042	0.008	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.16	0.16	-10000	0	-0.3	304	304
BCL2/BAX	0.027	0.011	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0.015	0.004	-10000	0	-10000	0	0
CaM/Ca2+	0.015	0.004	-10000	0	-10000	0	0
BAX	0.019	0.007	-10000	0	-10000	0	0
MAPK14	0.021	0.002	-10000	0	-10000	0	0
BAD	0.021	0.003	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.15	0.15	0.15	1	-0.33	230	231
Calcineurin A alpha-beta B1/BCL2	0.021	0.003	-10000	0	-10000	0	0
FKBP8	0.02	0.004	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.15	0.15	0.32	230	-0.15	1	231
KPNB1	0.021	0.002	-10000	0	-10000	0	0
KPNA2	0.021	0.003	-10000	0	-10000	0	0
XPO1	0.021	0.001	-10000	0	-10000	0	0
SFN	0.022	0.02	0.12	23	-10000	0	23
MAP3K8	0.021	0.016	0.12	12	-10000	0	12
NFAT4/CK1 alpha	0.002	0.046	-10000	0	-0.12	71	71
MEF2D/NFAT1/Cbp/p300	0.004	0.08	-10000	0	-0.22	37	37
CABIN1	-0.16	0.16	0.16	1	-0.34	242	243
CALM1	0.02	0.005	-10000	0	-10000	0	0
RAN	0.021	0.002	-10000	0	-10000	0	0
MAP3K1	0.024	0.018	0.12	21	-10000	0	21
CAMK4	0.015	0.01	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
MAPK3	0.021	0.002	-10000	0	-10000	0	0
YWHAH	0.02	0.005	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.034	0.088	-10000	0	-0.16	221	221
YWHAB	0.02	0.004	-10000	0	-10000	0	0
MAPK8	0.019	0.006	-10000	0	-10000	0	0
MAPK9	0.021	0.003	-10000	0	-10000	0	0
YWHAG	0.017	0.008	-10000	0	-10000	0	0
FKBP1A	0.02	0.004	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	-0.021	0.1	-10000	0	-0.28	33	33
PRKCH	0.02	0.004	-10000	0	-10000	0	0
CABIN1/Cbp/p300	0.03	0.007	-10000	0	-10000	0	0
CASP3	0.021	0.009	0.12	4	-10000	0	4
PIM1	0.021	0.007	0.12	3	-10000	0	3
Calcineurin A alpha-beta B1/FKBP12/FK506	0.014	0.003	-10000	0	-10000	0	0
apoptosis	0.008	0.021	-10000	0	-0.12	1	1
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0	0.04	-10000	0	-0.22	6	6
PRKCB	0.014	0.01	-10000	0	-10000	0	0
PRKCE	0.02	0.004	-10000	0	-10000	0	0
JNK2/NFAT4	-0.021	0.089	-10000	0	-0.19	141	141
BAD/BCL-XL	0.03	0.007	-10000	0	-10000	0	0
PRKCD	0.02	0.004	-10000	0	-10000	0	0
NUP214	0.021	0.003	-10000	0	-10000	0	0
PRKCZ	0.017	0.009	-10000	0	-10000	0	0
PRKCA	0.02	0.004	-10000	0	-10000	0	0
PRKCG	0.005	0.009	-10000	0	-10000	0	0
PRKCQ	0.018	0.008	0.12	1	-10000	0	1
FKBP38/BCL2	0.029	0.007	-10000	0	-10000	0	0
EP300	0.02	0.004	-10000	0	-0.021	1	1
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.02	0.004	-10000	0	-10000	0	0
NFATc/JNK1	-0.005	0.076	-10000	0	-0.3	13	13
CaM/Ca2+/FKBP38	0.026	0.008	-10000	0	-10000	0	0
FKBP12/FK506	0.015	0.003	-10000	0	-10000	0	0
CSNK1A1	-0.009	0.003	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.015	0.069	-10000	0	-0.13	181	181
NFATc/ERK1	-0.003	0.081	0.24	1	-0.3	13	14
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.16	0.16	-10000	0	-0.3	310	310
NR4A1	-0.017	0.062	-10000	0	-0.2	34	34
GSK3B	0.021	0.003	-10000	0	-10000	0	0
positive T cell selection	-0.016	0.081	-10000	0	-0.25	71	71
NFAT1/CK1 alpha	-0.014	0.05	-10000	0	-0.17	38	38
RCH1/ KPNB1	0.031	0.005	-10000	0	-10000	0	0
YWHAQ	0.021	0.002	-10000	0	-10000	0	0
PRKACA	0.02	0.004	-10000	0	-10000	0	0
AKAP5	0.013	0.01	-10000	0	-10000	0	0
MEF2D	0.021	0.003	-10000	0	-0.021	1	1
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.02	0.005	-10000	0	-10000	0	0
NFATc/p38 alpha	-0.003	0.08	0.24	1	-0.3	13	14
CREBBP	0.021	0.003	-10000	0	-0.021	1	1
BCL2	0.021	0.003	-10000	0	-10000	0	0

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.021	0.005	0.12	1	-10000	0	1
RAS family/GTP/Tiam1	0.001	0.034	-10000	0	-0.2	1	1
NT3 (dimer)/TRKC	0.027	0.017	-10000	0	-0.15	4	4
NT3 (dimer)/TRKB	0.045	0.029	0.18	2	-0.12	3	5
SHC/Grb2/SOS1/GAB1/PI3K	0.018	0.007	-10000	0	-10000	0	0
RAPGEF1	0.021	0.003	-10000	0	-10000	0	0
BDNF	0.01	0.011	-10000	0	-10000	0	0
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
DYNLT1	0.03	0.031	0.12	63	-10000	0	63
NTRK1	0.026	0.023	0.12	35	-10000	0	35
NTRK2	0.021	0.005	0.12	1	-10000	0	1
NTRK3	0.021	0.003	-10000	0	-10000	0	0
NT-4/5 (dimer)/TRKB	0.044	0.032	0.18	3	-0.13	2	5
neuron apoptosis	0.068	0.11	0.31	66	-10000	0	66
SHC 2-3/Grb2	-0.073	0.12	-10000	0	-0.33	66	66
SHC1	0.023	0.016	0.12	16	-10000	0	16
SHC2	-0.06	0.088	-10000	0	-0.24	66	66
SHC3	-0.085	0.14	-10000	0	-0.42	65	65
STAT3 (dimer)	0.027	0.013	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	0.049	0.03	0.18	6	-10000	0	6
RIN/GDP	-0.001	0.048	0.17	6	-0.25	4	10
GIPC1	0.02	0.004	-10000	0	-10000	0	0
KRAS	0.02	0.004	-10000	0	-10000	0	0
DNAJA3	-0.014	0.045	0.12	5	-0.15	34	39
RIN/GTP	-0.027	0.072	-10000	0	-0.15	168	168
CCND1	-0.002	0.031	0.27	2	-10000	0	2
MAGED1	0.021	0	-10000	0	-10000	0	0
PTPN11	0.021	0.003	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.019	0.02	0.12	22	-10000	0	22
SHC/GRB2/SOS1	0.042	0.014	-10000	0	-10000	0	0
GRB2	0.02	0.004	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.015	0.085	0.18	1	-0.14	197	198
TRKA/NEDD4-2	0.03	0.033	-10000	0	-0.16	15	15
ELMO1	0.018	0.008	-10000	0	-10000	0	0
RhoG/GTP/ELMO1/DOCK1	0.022	0.012	-10000	0	-10000	0	0
NGF	0.017	0.009	0.12	1	-10000	0	1
HRAS	0.02	0.005	-10000	0	-10000	0	0
DOCK1	0.018	0.007	-10000	0	-10000	0	0
GAB2	0.021	0.003	-10000	0	-10000	0	0
RIT2	0.015	0.009	-10000	0	-10000	0	0
RIT1	0.021	0.003	-10000	0	-10000	0	0
FRS2	0.02	0.004	-10000	0	-10000	0	0
DNM1	0.009	0.01	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.021	0.002	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	0.007	0.049	0.14	1	-0.14	29	30
mol:GDP	0	0.065	0.23	9	-0.37	4	13
NGF (dimer)	0.017	0.009	0.12	1	-10000	0	1
RhoG/GDP	0.013	0.006	-10000	0	-10000	0	0
RIT1/GDP	0.005	0.05	0.2	8	-0.24	4	12
TIAM1	0.02	0.004	-10000	0	-10000	0	0
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.048	0.087	-10000	0	-0.13	340	340
KIDINS220/CRKL/C3G	0.03	0.007	0.11	1	-10000	0	1
SHC/RasGAP	0.032	0.013	-10000	0	-10000	0	0
FRS2 family/SHP2	0.041	0.009	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0.052	0.017	-10000	0	-10000	0	0
RIT1/GTP	0.015	0.002	-10000	0	-10000	0	0
NT3 (dimer)	0.019	0.011	0.12	6	-10000	0	6
RAP1/GDP	0.004	0.037	0.11	1	-0.21	4	5
KIDINS220/CRKL	0.021	0.005	0.12	1	-10000	0	1
BDNF (dimer)	0.01	0.01	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.026	0.053	0.18	1	-0.13	55	56
Schwann cell development	-0.018	0.015	-10000	0	-0.044	91	91
EHD4	0.022	0.012	0.12	8	-10000	0	8
FRS2 family/GRB2/SOS1	0.051	0.014	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.016	0.03	-10000	0	-0.2	7	7
RAP1B	0.021	0.009	0.12	4	-10000	0	4
RAP1A	0.019	0.007	-10000	0	-10000	0	0
CDC42/GTP	-0.038	0.071	-10000	0	-0.11	304	304
ABL1	0.021	0.003	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.03	0.006	-10000	0	-10000	0	0
Rap1/GTP	-0.042	0.082	-10000	0	-0.25	54	54
STAT3	0.027	0.013	-10000	0	-10000	0	0
axon guidance	-0.041	0.065	-10000	0	-0.11	304	304
MAPK3	-0.046	0.057	0.14	3	-0.13	194	197
MAPK1	-0.045	0.057	0.18	2	-0.13	188	190
CDC42/GDP	0.009	0.045	0.17	8	-0.24	4	12
NTF3	0.019	0.011	0.12	6	-10000	0	6
NTF4	0.019	0.021	0.12	22	-10000	0	22
NGF (dimer)/TRKA/FAIM	0.03	0.047	0.18	1	-0.13	40	41
PI3K	0.03	0.006	-10000	0	-10000	0	0
FRS3	0.021	0.002	-10000	0	-10000	0	0
FAIM	0.021	0.002	-10000	0	-10000	0	0
GAB1	0.021	0.003	-10000	0	-10000	0	0
RASGRF1	-0.016	0.049	0.13	2	-0.18	38	40
SOS1	0.021	0.001	-10000	0	-10000	0	0
MCF2L	-0.014	0.011	-10000	0	-0.13	4	4
RGS19	0.02	0.004	-10000	0	-10000	0	0
CDC42	0.019	0.006	-10000	0	-10000	0	0
RAS family/GTP	-0.003	0.053	-10000	0	-0.4	4	4
Rac1/GDP	0.005	0.044	0.2	5	-0.35	1	6
NGF (dimer)/TRKA/GRIT	0.019	0.042	0.098	35	-0.13	41	76
neuron projection morphogenesis	0.009	0.065	-10000	0	-0.93	1	1
NGF (dimer)/TRKA/NEDD4-2	0.026	0.053	0.18	1	-0.13	55	56
MAP2K1	-0.009	0.042	0.17	33	-10000	0	33
NGFR	0.034	0.035	0.12	84	-10000	0	84
NGF (dimer)/TRKA/GIPC/GAIP	-0.082	0.11	-10000	0	-0.18	320	320
RAS family/GTP/PI3K	0.012	0.012	-10000	0	-0.17	2	2
FRS2 family/SHP2/GRB2/SOS1	0.058	0.017	-10000	0	-10000	0	0
NRAS	0.019	0.007	-10000	0	-10000	0	0
GRB2/SOS1	0.03	0.006	-10000	0	-10000	0	0
PRKCI	0.021	0.003	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.018	0.008	-10000	0	-10000	0	0
PRKCZ	0.016	0.009	-10000	0	-10000	0	0
MAPKKK cascade	-0.046	0.19	-10000	0	-0.44	114	114
RASA1	0.021	0.002	-10000	0	-10000	0	0
TRKA/c-Abl	0.034	0.018	0.11	35	-10000	0	35
SQSTM1	0.021	0.003	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.035	0.087	-10000	0	-0.12	331	331
NGF (dimer)/TRKA/p62/Atypical PKCs	0.027	0.07	-10000	0	-0.12	99	99
MATK	0.015	0.01	-10000	0	-10000	0	0
NEDD4L	0.02	0.005	-10000	0	-10000	0	0
RAS family/GDP	-0.007	0.026	-10000	0	-0.16	5	5
NGF (dimer)/TRKA	0	0.05	0.14	3	-0.15	34	37
Rac1/GTP	-0.019	0.05	-10000	0	-0.16	23	23
FRS2 family/SHP2/CRK family	0.059	0.016	-10000	0	-10000	0	0

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.03	0.025	0.17	1	-10000	0	1
NF kappa B1 p50/RelA/I kappa B alpha	0.032	0.039	0.27	4	-10000	0	4
alphaV/beta3 Integrin/Osteopontin/Src	0.045	0.032	0.12	44	-0.15	3	47
AP1	0.052	0.053	0.2	5	-0.18	1	6
ILK	0.006	0.031	0.19	2	-10000	0	2
bone resorption	0.023	0.06	0.18	22	-10000	0	22
PTK2B	0.021	0.003	-10000	0	-10000	0	0
PYK2/p130Cas	0.069	0.04	0.17	33	-0.11	3	36
ITGAV	0.023	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.058	0.039	0.11	248	-0.15	2	250
alphaV/beta3 Integrin/Osteopontin	0.073	0.051	0.2	58	-0.13	3	61
MAP3K1	0.008	0.035	0.084	49	-0.12	3	52
JUN	0.019	0.007	-10000	0	-10000	0	0
MAPK3	0.005	0.033	0.18	1	-10000	0	1
MAPK1	0.004	0.033	0.18	1	-10000	0	1
Rac1/GDP	0.013	0.006	-10000	0	-10000	0	0
NFKB1	0.021	0.002	-10000	0	-10000	0	0
MAPK8	-0.002	0.025	0.18	2	-10000	0	2
ITGB3	0.043	0.042	0.13	124	-10000	0	124
NFKBIA	0.007	0.028	0.17	1	-0.17	1	2
FOS	0.022	0.013	0.12	8	-10000	0	8
CD44	0.06	0.051	0.12	252	-10000	0	252
CHUK	0.019	0.006	-10000	0	-10000	0	0
PLAU	0.018	0.05	0.28	2	-10000	0	2
NF kappa B1 p50/RelA	0.046	0.035	0.19	5	-10000	0	5
BCAR1	0.021	0.003	-10000	0	-10000	0	0
RELA	0.021	0.003	-10000	0	-10000	0	0
alphaV beta3 Integrin	0.05	0.032	0.12	101	-10000	0	101
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	0.005	0.031	0.1	11	-0.12	3	14
VAV3	0.001	0.025	0.19	4	-10000	0	4
MAP3K14	0.009	0.035	0.08	55	-0.12	3	58
ROCK2	0.021	0.002	-10000	0	-10000	0	0
SPP1	0.038	0.038	0.13	96	-10000	0	96
RAC1	0.018	0.008	-10000	0	-10000	0	0
Rac1/GTP	-0.007	0.036	0.16	2	-10000	0	2
MMP2	0.015	0.059	0.21	13	-10000	0	13

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.048	0.028	0.21	5	-0.12	1	6
MAP4K1	0.02	0.011	0.12	5	-10000	0	5
MAP3K8	0.021	0.016	0.12	12	-10000	0	12
PRKCB	0.014	0.01	-10000	0	-10000	0	0
DBNL	0.018	0.008	-10000	0	-10000	0	0
CRKL	0.021	0.005	0.12	1	-10000	0	1
MAP3K1	0.011	0.039	0.12	1	-0.26	2	3
JUN	-0.17	0.27	-10000	0	-0.53	224	224
MAP3K7	0.01	0.035	-10000	0	-0.16	2	2
GRAP2	0.023	0.018	0.12	19	-10000	0	19
CRK	0.021	0.002	-10000	0	-10000	0	0
MAP2K4	0.007	0.044	0.18	5	-0.52	1	6
LAT	0.021	0.006	0.12	2	-10000	0	2
LCP2	0.021	0.009	0.12	4	-10000	0	4
MAPK8	-0.18	0.28	-10000	0	-0.56	226	226
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.018	0.042	-10000	0	-0.22	4	4
LAT/GRAP2/SLP76/HPK1/HIP-55	0.048	0.034	0.21	5	-0.12	1	6

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.038	0.029	0.11	83	-0.16	3	86
ATM	0.021	0.003	-10000	0	-10000	0	0
UBE2D3	0.021	0.002	-10000	0	-10000	0	0
PRKDC	0.021	0.003	-10000	0	-10000	0	0
ATR	0.021	0.003	-10000	0	-10000	0	0
UBE2L3	0.021	0.003	-10000	0	-10000	0	0
FANCD2	0.023	0.018	-10000	0	-10000	0	0
protein ubiquitination	0.07	0.05	0.18	65	-0.12	3	68
XRCC5	0.021	0.001	-10000	0	-10000	0	0
XRCC6	0.02	0.004	-10000	0	-10000	0	0
M/R/N Complex	0.04	0.012	-10000	0	-10000	0	0
MRE11A	0.021	0.003	-10000	0	-10000	0	0
DNA-PK	0.04	0.01	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.019	0.063	0.19	1	-0.47	7	8
FANCF	0.021	0.003	-10000	0	-10000	0	0
BRCA1	0.024	0.017	0.12	18	-10000	0	18
CCNE1	0.019	0.007	-10000	0	-10000	0	0
CDK2/Cyclin E1	0.048	0.037	-10000	0	-10000	0	0
FANCG	0.02	0.006	0.12	1	-10000	0	1
BRCA1/BACH1/BARD1	0.043	0.034	0.18	11	-0.16	3	14
FANCE	0.021	0.002	-10000	0	-10000	0	0
FANCC	0.034	0.035	0.12	85	-10000	0	85
NBN	0.02	0.005	-10000	0	-10000	0	0
FANCA	0.022	0.01	0.12	6	-10000	0	6
DNA repair	0.018	0.057	0.23	22	-0.4	2	24
BRCA1/BARD1/ubiquitin	0.043	0.034	0.18	11	-0.16	3	14
BARD1/DNA-PK	0.059	0.028	-10000	0	-0.12	2	2
FANCL	0.021	0.002	-10000	0	-10000	0	0
mRNA polyadenylation	-0.038	0.029	0.16	3	-0.1	83	86
BRCA1/BARD1/CTIP/M/R/N Complex	0.017	0.02	0.15	3	-0.16	2	5
BRCA1/BACH1/BARD1/TopBP1	0.052	0.031	0.18	10	-0.13	3	13
BRCA1/BARD1/P53	0.068	0.041	0.19	33	-0.12	3	36
BARD1/CSTF1/BRCA1	0.05	0.032	0.18	11	-0.13	3	14
BRCA1/BACH1	0.024	0.017	0.12	18	-10000	0	18
BARD1	0.036	0.036	0.12	95	-10000	0	95
PCNA	0.027	0.027	0.12	46	-10000	0	46
BRCA1/BARD1/UbcH5C	0.052	0.031	0.18	9	-0.13	3	12
BRCA1/BARD1/UbcH7	0.051	0.031	0.18	8	-0.13	3	11
BRCA1/BARD1/RAD51/PCNA	0.084	0.06	0.2	90	-0.11	3	93
BARD1/DNA-PK/P53	0.07	0.036	0.18	20	-0.11	2	22
BRCA1/BARD1/Ubiquitin	0.043	0.034	0.18	11	-0.16	3	14
BRCA1/BARD1/CTIP	0.045	0.037	0.17	29	-0.12	3	32
FA complex	0.017	0.024	-10000	0	-0.17	5	5
BARD1/EWS	0.04	0.03	0.11	90	-0.16	3	93
RBBP8	-0.008	0.016	0.051	47	-10000	0	47
TP53	0.031	0.031	0.12	67	-10000	0	67
TOPBP1	0.021	0.003	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.066	0.04	0.12	3	-0.19	33	36
BRCA1/BARD1	0.076	0.054	0.19	65	-0.12	3	68
CSTF1	0.02	0.004	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.025	0.029	0.089	95	-0.15	3	98
CDK2	0.051	0.048	0.12	198	-10000	0	198
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.059	0.05	0.12	242	-10000	0	242
RAD50	0.021	0.002	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.043	0.034	0.18	11	-0.16	3	14
EWSR1	0.02	0.004	-10000	0	-10000	0	0

×

IL4-mediated signaling events

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
BCL2L1	-0.16	0.31	0.62	2	-0.99	8	10
STAT6 (cleaved dimer)	-0.2	0.32	-10000	0	-0.91	34	34
IGHG1	-0.058	0.14	0.38	2	-10000	0	2
IGHG3	-0.16	0.29	-10000	0	-0.96	8	8
AKT1	-0.12	0.25	0.4	3	-0.75	38	41
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.092	0.22	0.39	2	-0.79	25	27
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.12	0.25	0.42	2	-0.74	42	44
THY1	-0.18	0.33	-10000	0	-1.1	18	18
MYB	0.03	0.031	0.12	63	-10000	0	63
HMGA1	0.021	0.005	0.12	1	-10000	0	1
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.14	0.26	0.41	7	-0.69	44	51
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.12	0.25	0.42	2	-0.74	42	44
SP1	0.027	0.012	-10000	0	-10000	0	0
INPP5D	0.021	0.009	0.12	5	-10000	0	5
SOCS5	0.021	0.029	-10000	0	-0.056	7	7
STAT6 (dimer)/ETS1	-0.18	0.33	0.6	1	-0.94	26	27
SOCS1	-0.14	0.28	0.42	12	-0.65	39	51
SOCS3	-0.18	0.36	0.52	2	-1.1	57	59
FCER2	-0.58	0.62	0.5	1	-1.2	339	340
PARP14	-0.009	0.045	0.11	29	-0.048	325	354
CCL17	-0.17	0.3	-10000	0	-0.99	8	8
GRB2	0.02	0.004	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.088	0.19	0.38	3	-0.58	23	26
T cell proliferation	-0.18	0.32	-10000	0	-0.98	14	14
IL4R/JAK1	-0.17	0.31	-10000	0	-1	8	8
EGR2	-0.28	0.4	-10000	0	-1.1	42	42
JAK2	-0.006	0.045	0.11	8	-10000	0	8
JAK3	0.01	0.02	-10000	0	-0.041	24	24
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
JAK1	0.004	0.028	0.077	7	-10000	0	7
COL1A2	-0.044	0.15	-10000	0	-0.73	2	2
CCL26	-0.13	0.34	0.6	10	-1	7	17
IL4R	-0.18	0.32	0.61	1	-1	8	9
PTPN6	0.017	0.024	0.11	4	-0.046	1	5
IL13RA2	-0.33	0.55	-10000	0	-1.2	153	153
IL13RA1	-0.003	0.048	0.12	10	-10000	0	10
IRF4	-0.065	0.15	0.4	1	-0.79	8	9
ARG1	-0.047	0.13	0.36	1	-0.93	1	2
CBL	-0.13	0.24	0.39	4	-0.66	43	47
GTF3A	0.029	0.024	-10000	0	-0.12	8	8
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
IL13RA1/JAK2	0	0.066	0.16	14	-10000	0	14
IRF4/BCL6	-0.017	0.13	-10000	0	-0.78	6	6
CD40LG	0.002	0.033	0.12	22	-0.078	2	24
MAPK14	-0.15	0.28	0.41	4	-0.77	55	59
mitosis	-0.11	0.24	0.39	3	-0.7	38	41
STAT6	-0.18	0.34	0.62	2	-1.1	8	10
SPI1	0.024	0.014	0.13	10	-10000	0	10
RPS6KB1	-0.11	0.23	0.4	4	-0.69	36	40
STAT6 (dimer)	-0.18	0.33	0.62	2	-1.1	8	10
STAT6 (dimer)/PARP14	-0.24	0.36	-10000	0	-0.94	30	30
mast cell activation	0.005	0.013	-10000	0	-0.034	5	5
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.1	0.23	0.42	3	-0.74	25	28
FRAP1	-0.12	0.25	0.4	3	-0.75	38	41
LTA	-0.17	0.3	0.57	1	-0.99	8	9
FES	0.021	0.005	0.12	1	-10000	0	1
T-helper 1 cell differentiation	0.18	0.33	1.1	8	-0.62	2	10
CCL11	-0.17	0.29	-10000	0	-0.96	8	8
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.11	0.23	0.43	2	-0.75	25	27
IL2RG	0.024	0.04	0.12	78	-0.042	24	102
IL10	-0.16	0.31	0.57	2	-0.99	8	10
IRS1	0.021	0.001	-10000	0	-10000	0	0
IRS2	0.02	0.004	-10000	0	-10000	0	0
IL4	-0.041	0.13	-10000	0	-0.93	4	4
IL5	-0.17	0.3	-10000	0	-0.99	8	8
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.15	0.28	0.55	2	-0.79	11	13
COL1A1	-0.066	0.23	0.43	2	-0.92	24	26
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.17	0.3	-10000	0	-1	8	8
IL2R gamma/JAK3	0.018	0.05	0.11	40	-0.15	21	61
TFF3	-0.17	0.31	0.58	2	-0.99	8	10
ALOX15	-0.17	0.3	-10000	0	-0.99	8	8
MYBL1	0.021	0.01	0.12	5	-10000	0	5
T-helper 2 cell differentiation	-0.17	0.3	0.5	2	-0.8	28	30
SHC1	0.023	0.016	0.12	16	-10000	0	16
CEBPB	0.022	0.008	0.13	2	-10000	0	2
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.12	0.25	0.42	2	-0.72	45	47
mol:PI-3-4-5-P3	-0.12	0.25	0.4	3	-0.75	38	41
PI3K	-0.12	0.26	0.4	3	-0.8	38	41
DOK2	0.026	0.024	0.12	36	-10000	0	36
ETS1	0.021	0.033	0.13	22	-0.054	5	27
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.08	0.18	0.33	8	-0.52	26	34
ITGB3	-0.16	0.31	0.57	1	-0.99	8	9
PIGR	-0.16	0.31	0.57	1	-0.99	8	9
IGHE	0.017	0.044	0.15	13	-0.12	3	16
MAPKKK cascade	-0.079	0.18	0.33	8	-0.52	26	34
BCL6	0.032	0.014	0.061	29	-0.018	1	30
OPRM1	-0.19	0.35	-10000	0	-1.3	22	22
RETNLB	-0.17	0.3	-10000	0	-0.99	8	8
SELP	-0.17	0.31	0.57	2	-0.99	8	10
AICDA	-0.16	0.29	-10000	0	-0.94	8	8

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	0.059	0.031	-10000	0	-0.11	2	2
SMAD6-7/SMURF1	0.033	0.018	-10000	0	-10000	0	0
NOG	0.04	0.041	0.12	124	-10000	0	124
SMAD9	0	0.11	-10000	0	-0.4	42	42
SMAD4	0.021	0.003	-10000	0	-10000	0	0
SMAD5	0.004	0.054	-10000	0	-0.27	16	16
BMP7/USAG1	-0.051	0.089	-10000	0	-0.16	268	268
SMAD5/SKI	0.011	0.063	-10000	0	-0.28	19	19
SMAD1	0.006	0.05	-10000	0	-0.34	6	6
BMP2	0.079	0.052	0.12	378	-10000	0	378
SMAD1/SMAD1/SMAD4	0.018	0.045	-10000	0	-0.25	10	10
BMPR1A	0.019	0.006	-10000	0	-10000	0	0
BMPR1B	0.021	0.003	-10000	0	-10000	0	0
BMPR1A-1B/BAMBI	0.036	0.018	-10000	0	-0.13	2	2
AHSG	0.023	0.016	0.12	15	-10000	0	15
CER1	0.027	0.031	0.12	60	-10000	0	60
BMP2-4/CER1	0.078	0.044	0.18	17	-0.13	1	18
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	0.015	0.054	-10000	0	-0.24	8	8
BMP2-4 (homodimer)	0.072	0.044	0.11	374	-0.16	1	375
RGMB	0.021	0.002	-10000	0	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	0.047	0.021	-10000	0	-0.11	2	2
RGMA	0.023	0.014	0.12	12	-10000	0	12
SMURF1	0.017	0.009	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	0.016	0.04	-10000	0	-0.2	3	3
BMP2-4/USAG1	-0.014	0.098	0.18	5	-0.12	269	274
SMAD6/SMURF1/SMAD5	0.011	0.057	-10000	0	-0.28	14	14
SOSTDC1	0.009	0.01	-10000	0	-10000	0	0
BMP7/BMPR2/BMPR1A-1B	0.047	0.021	-10000	0	-0.11	2	2
SKI	0.019	0.007	-10000	0	-10000	0	0
BMP6 (homodimer)	0.021	0.009	0.12	5	-10000	0	5
HFE2	0.018	0.005	-10000	0	-10000	0	0
ZFYVE16	0.021	0.002	-10000	0	-10000	0	0
MAP3K7	0.02	0.004	-10000	0	-10000	0	0
BMP2-4/CHRD	0.076	0.047	0.18	13	-0.13	7	20
SMAD5/SMAD5/SMAD4	0.01	0.066	-10000	0	-0.27	22	22
MAPK1	0.021	0.003	-10000	0	-10000	0	0
TAK1/TAB family	0.022	0.041	-10000	0	-0.22	2	2
BMP7 (homodimer)	0.02	0.004	-10000	0	-10000	0	0
NUP214	0.021	0.003	-10000	0	-10000	0	0
BMP6/FETUA	0.032	0.014	-10000	0	-10000	0	0
SMAD1/SKI	0.014	0.057	-10000	0	-0.3	11	11
SMAD6	0.021	0.006	0.12	2	-10000	0	2
CTDSP2	0.019	0.006	-10000	0	-10000	0	0
BMP2-4/FETUA	0.08	0.044	0.18	27	-0.13	1	28
MAP3K7IP1	0	0	-10000	0	-10000	0	0
GREM1	0.017	0.01	0.12	1	-10000	0	1
BMPR2 (homodimer)	0.021	0.001	-10000	0	-10000	0	0
GADD34/PP1CA	0.037	0.015	-10000	0	-10000	0	0
BMPR1A-1B (homodimer)	0.027	0.014	-10000	0	-0.16	2	2
CHRDL1	0.02	0.009	0.12	3	-10000	0	3
ENDOFIN/SMAD1	0.016	0.058	-10000	0	-0.3	11	11
SMAD6-7/SMURF1/SMAD1	0.027	0.054	-10000	0	-0.28	10	10
SMAD6/SMURF1	0.017	0.008	-10000	0	-10000	0	0
BAMBI	0.019	0.009	0.12	2	-10000	0	2
SMURF2	0.021	0.003	-10000	0	-10000	0	0
BMP2-4/CHRDL1	0.062	0.07	0.18	14	-0.13	55	69
BMP2-4/GREM1	0.038	0.087	0.18	9	-0.12	127	136
SMAD7	0.021	0.003	-10000	0	-10000	0	0
SMAD8A/SMAD8A/SMAD4	0.003	0.12	-10000	0	-0.37	53	53
SMAD1/SMAD6	0.013	0.05	-10000	0	-0.29	10	10
TAK1/SMAD6	0.024	0.013	-10000	0	-10000	0	0
BMP7	0.02	0.004	-10000	0	-10000	0	0
BMP6	0.021	0.009	0.12	5	-10000	0	5
MAP3K7IP2	0	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	0.02	0.044	-10000	0	-0.23	4	4
PPM1A	0.02	0.004	-10000	0	-10000	0	0
SMAD1/SMURF2	0.016	0.058	-10000	0	-0.3	11	11
SMAD7/SMURF1	0.024	0.013	-10000	0	-10000	0	0
CTDSPL	0.021	0.002	-10000	0	-10000	0	0
PPP1CA	0.021	0.003	-10000	0	-10000	0	0
XIAP	0.021	0.001	-10000	0	-10000	0	0
CTDSP1	0.021	0.004	0.12	1	-10000	0	1
PPP1R15A	0.019	0.007	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	0.015	0.044	-10000	0	-0.2	2	2
CHRD	0.02	0.004	-10000	0	-10000	0	0
BMPR2	0.021	0.001	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	0.016	0.04	0.13	1	-0.16	9	10
BMP4	0.023	0.017	0.12	18	-10000	0	18
FST	0.033	0.034	0.12	79	-10000	0	79
BMP2-4/NOG	0.089	0.059	0.18	126	-0.13	2	128
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	0.047	0.029	-10000	0	-0.1	2	2

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	0.04	0.011	-10000	0	-10000	0	0
fibroblast growth factor receptor signaling pathway	0.04	0.011	-10000	0	-10000	0	0
LAMA1	0.025	0.022	0.12	30	-10000	0	30
PRNP	0.02	0.004	-10000	0	-10000	0	0
GPC1/SLIT2	-0.03	0.088	0.11	3	-0.16	214	217
SMAD2	-0.016	0.008	-10000	0	-0.12	1	1
GPC1/PrPc/Cu2+	0.026	0.01	0.096	1	-0.13	1	2
GPC1/Laminin alpha1	0.031	0.026	-10000	0	-0.15	7	7
TDGF1	0.02	0.006	0.12	1	-10000	0	1
CRIPTO/GPC1	0.025	0.034	-10000	0	-0.16	19	19
APP/GPC1	0.03	0.011	-10000	0	-0.16	1	1
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.017	0.022	-10000	0	-0.14	19	19
FLT1	0.02	0.005	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	0.041	0.014	-10000	0	-0.13	1	1
SERPINC1	0.026	0.025	0.12	40	-10000	0	40
FYN	-0.017	0.019	-10000	0	-0.13	16	16
FGR	-0.015	0.022	0.062	6	-0.14	16	22
positive regulation of MAPKKK cascade	-0.002	0.066	0.18	32	-0.23	22	54
SLIT2	0.014	0.012	0.12	2	-10000	0	2
GPC1/NRG	-0.006	0.074	-10000	0	-0.16	128	128
NRG1	0.016	0.009	-10000	0	-10000	0	0
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.046	0.026	0.18	1	-0.13	1	2
LYN	-0.017	0.021	0.062	3	-0.13	18	21
mol:Spermine	-0.006	0.002	0.049	1	-10000	0	1
cell growth	0.04	0.011	-10000	0	-10000	0	0
BMP signaling pathway	-0.021	0.005	-10000	0	-0.12	1	1
SRC	-0.017	0.02	-10000	0	-0.14	16	16
TGFBR1	0.021	0.009	0.12	4	-10000	0	4
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	0.032	0.041	0.12	105	-10000	0	105
GPC1	0.021	0.005	0.12	1	-10000	0	1
TGFBR1 (dimer)	0.021	0.009	0.12	4	-10000	0	4
VEGFA	0.033	0.034	0.12	79	-10000	0	79
BLK	-0.006	0.034	0.062	98	-0.13	18	116
HCK	-0.015	0.023	0.062	11	-0.14	16	27
FGF2	0.021	0.005	0.12	1	-10000	0	1
FGFR1	0.021	0.003	-10000	0	-10000	0	0
VEGFR1 homodimer	0.02	0.005	-10000	0	-10000	0	0
TGFBR2	0.021	0.007	0.12	3	-10000	0	3
cell death	0.029	0.01	-10000	0	-0.16	1	1
ATIII/GPC1	0.034	0.019	-10000	0	-10000	0	0
PLA2G2A/GPC1	0.028	0.054	0.11	104	-0.16	35	139
LCK	-0.002	0.036	0.062	122	-0.14	16	138
neuron differentiation	-0.006	0.074	-10000	0	-0.16	128	128
PrPc/Cu2+	0.015	0.003	-10000	0	-10000	0	0
APP	0.021	0.003	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.021	0.007	0.12	3	-10000	0	3

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.057	0.088	0.18	6	-0.24	32	38
TBX21	-0.045	0.18	-10000	0	-0.79	20	20
B2M	0.032	0.032	0.12	68	-10000	0	68
TYK2	0.024	0.018	-10000	0	-10000	0	0
IL12RB1	0.024	0.019	0.097	3	-0.054	3	6
GADD45B	-0.007	0.14	-10000	0	-0.6	10	10
IL12RB2	0.007	0.015	0.081	1	-0.055	2	3
GADD45G	0.004	0.14	-10000	0	-0.62	8	8
natural killer cell activation	0.014	0.013	0.038	54	-0.039	4	58
RELB	0.019	0.007	-10000	0	-10000	0	0
RELA	0.021	0.003	-10000	0	-10000	0	0
IL18	0.028	0.025	0.13	29	-0.032	2	31
IL2RA	0.039	0.045	0.12	139	-10000	0	139
IFNG	0.017	0.01	0.12	5	-10000	0	5
STAT3 (dimer)	-0.016	0.15	0.34	4	-0.63	23	27
HLA-DRB5	0	0.002	-10000	0	-0.02	4	4
FASLG	-0.046	0.18	0.57	1	-0.79	21	22
NF kappa B2 p52/RelB	-0.042	0.18	-10000	0	-0.74	26	26
CD4	0.021	0.015	0.12	11	-0.03	7	18
SOCS1	0.052	0.048	0.12	202	-10000	0	202
EntrezGene:6955	0.001	0.003	-10000	0	-0.022	7	7
CD3D	0.033	0.036	0.13	83	-0.034	7	90
CD3E	0.03	0.032	0.13	60	-0.03	7	67
CD3G	0.028	0.031	0.13	55	-0.035	7	62
IL12Rbeta2/JAK2	-0.083	0.088	0.13	1	-0.15	417	418
CCL3	-0.061	0.25	-10000	0	-1.1	26	26
CCL4	-0.061	0.25	0.41	1	-1.1	26	27
HLA-A	0.001	0.001	-10000	0	-10000	0	0
IL18/IL18R	0.077	0.051	0.2	51	-0.13	3	54
NOS2	-0.007	0.18	-10000	0	-0.78	25	25
IL12/IL12R/TYK2/JAK2/SPHK2	-0.058	0.09	0.17	3	-0.24	38	41
IL1R1	-0.047	0.18	-10000	0	-0.8	20	20
IL4	-0.025	0.019	-10000	0	-0.061	19	19
JAK2	0.024	0.018	0.078	1	-0.055	2	3
EntrezGene:6957	0.001	0.002	-10000	0	-0.02	4	4
TCR/CD3/MHC I/CD8	0.011	0.057	-10000	0	-0.48	1	1
RAB7A	0.01	0.13	-10000	0	-0.67	3	3
lysosomal transport	0.011	0.13	-10000	0	-0.6	4	4
FOS	-0.03	0.2	-10000	0	-0.72	38	38
STAT4 (dimer)	-0.11	0.19	0.4	4	-0.7	28	32
STAT5A (dimer)	-0.042	0.18	0.38	2	-0.73	27	29
GZMA	-0.028	0.18	-10000	0	-0.79	19	19
GZMB	-0.032	0.18	-10000	0	-0.77	21	21
HLX	0.022	0.012	0.12	9	-10000	0	9
LCK	-0.044	0.19	0.38	3	-0.78	26	29
TCR/CD3/MHC II/CD4	0.014	0.038	0.12	8	-0.17	7	15
IL2/IL2R	0.067	0.06	0.22	69	-0.12	1	70
MAPK14	0.01	0.15	0.38	1	-0.63	13	14
CCR5	-0.009	0.15	0.39	4	-0.66	14	18
IL1B	0.025	0.019	0.15	4	-10000	0	4
STAT6	-0.009	0.078	0.22	2	-0.41	10	12
STAT4	0.009	0.01	-10000	0	-10000	0	0
STAT3	0.021	0.002	-10000	0	-10000	0	0
STAT1	0.022	0.011	0.12	7	-10000	0	7
NFKB1	0.021	0.002	-10000	0	-10000	0	0
NFKB2	0.019	0.006	-10000	0	-10000	0	0
IL12B	0.029	0.021	0.11	6	-0.056	2	8
CD8A	0.02	0.008	0.13	2	-10000	0	2
CD8B	0.025	0.018	0.13	19	-10000	0	19
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.058	0.088	0.24	32	-0.18	6	38
IL2RB	0.03	0.031	0.12	63	-10000	0	63
proteasomal ubiquitin-dependent protein catabolic process	-0.11	0.18	0.39	4	-0.65	28	32
IL2RG	0.033	0.033	0.12	78	-10000	0	78
IL12	0.046	0.031	0.14	10	-10000	0	10
STAT5A	0.021	0.002	-10000	0	-10000	0	0
CD247	0.021	0.006	-10000	0	-0.03	7	7
IL2	0.015	0.002	-10000	0	-10000	0	0
SPHK2	0.019	0.007	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.027	0.022	0.12	12	-0.055	2	14
IL12/IL12R/TYK2/JAK2	-0.048	0.19	0.4	3	-0.81	26	29
MAP2K3	0.006	0.15	0.39	1	-0.62	13	14
RIPK2	0.02	0.007	0.12	2	-10000	0	2
MAP2K6	0.005	0.15	-10000	0	-0.61	13	13
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0	0.002	-10000	0	-0.023	7	7
IL18RAP	0.035	0.036	0.13	76	-0.032	2	78
IL12Rbeta1/TYK2	0.036	0.027	-10000	0	-0.15	1	1
EOMES	0.017	0.052	-10000	0	-0.59	3	3
STAT1 (dimer)	-0.013	0.16	0.37	4	-0.62	22	26
T cell proliferation	-0.027	0.15	0.34	5	-0.52	22	27
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.026	0.02	0.13	16	-10000	0	16
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.07	0.16	0.33	3	-0.56	27	30
ATF2	0.006	0.14	0.36	1	-0.59	13	14

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.027	0.024	0.12	39	-10000	0	39
ANTXR2	0.034	0.035	0.12	86	-10000	0	86
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.001	0.002	-10000	0	-10000	0	0
monocyte activation	-0.026	0.14	-10000	0	-0.34	109	109
MAP2K2	0.01	0.039	-10000	0	-0.56	3	3
MAP2K1	-0.005	0.002	-10000	0	-10000	0	0
MAP2K7	-0.005	0.002	-10000	0	-10000	0	0
MAP2K6	-0.005	0.002	-10000	0	-10000	0	0
CYAA	-0.005	0.007	-10000	0	-10000	0	0
MAP2K4	-0.005	0.002	-10000	0	-10000	0	0
IL1B	-0.013	0.031	-10000	0	-0.1	70	70
Channel	0.039	0.027	0.095	118	-10000	0	118
NLRP1	-0.005	0.002	-10000	0	-10000	0	0
CALM1	0.02	0.005	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.009	0.084	-10000	0	-0.38	31	31
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.001	0.002	-10000	0	-10000	0	0
MAPK3	-0.005	0.002	-10000	0	-10000	0	0
MAPK1	-0.005	0.002	-10000	0	-10000	0	0
PGR	-0.005	0.002	0.013	1	-10000	0	1
PA/Cellular Receptors	0.041	0.029	0.1	118	-10000	0	118
apoptosis	-0.001	0.002	-10000	0	-10000	0	0
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.038	0.027	0.092	118	-10000	0	118
macrophage activation	-0.008	0.002	-10000	0	-10000	0	0
TNF	0.021	0.015	0.12	11	-10000	0	11
VCAM1	-0.026	0.14	-10000	0	-0.34	108	108
platelet activation	-0.009	0.084	-10000	0	-0.38	31	31
MAPKKK cascade	0	0.017	-10000	0	-0.07	36	36
IL18	-0.002	0.01	0.19	1	-10000	0	1
negative regulation of macrophage activation	-0.001	0.002	-10000	0	-10000	0	0
LEF	-0.001	0.002	-10000	0	-10000	0	0
CASP1	0.001	0.006	0.017	44	-10000	0	44
mol:cAMP	-0.01	0.084	-10000	0	-0.39	31	31
necrosis	-0.001	0.002	-10000	0	-10000	0	0
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.038	0.027	0.093	118	-10000	0	118
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	0.032	0.071	0.21	22	-0.28	5	27
FYN	0.018	0.077	0.19	34	-0.31	6	40
LAT/GRAP2/SLP76	0.024	0.07	0.2	25	-0.27	6	31
IKBKB	0.021	0.003	-10000	0	-10000	0	0
AKT1	0.017	0.07	0.18	38	-0.3	4	42
B2M	0.032	0.032	0.13	68	-0.032	2	70
IKBKG	0.003	0.027	0.072	40	-0.12	1	41
MAP3K8	0.021	0.016	0.12	12	-10000	0	12
mol:Ca2+	-0.01	0.008	-10000	0	-0.041	2	2
integrin-mediated signaling pathway	0.025	0.009	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.019	0.081	0.2	33	-0.4	4	37
TRPV6	0.21	0.53	1.2	136	-10000	0	136
CD28	0.026	0.022	0.13	30	-0.016	3	33
SHC1	0.015	0.075	0.23	19	-0.28	9	28
receptor internalization	0.015	0.067	0.19	7	-0.25	13	20
PRF1	-0.033	0.2	-10000	0	-0.58	68	68
KRAS	0.02	0.004	-10000	0	-10000	0	0
GRB2	0.02	0.004	-10000	0	-10000	0	0
COT/AKT1	0.02	0.062	0.18	32	-0.25	3	35
LAT	0.012	0.069	0.18	16	-0.28	9	25
EntrezGene:6955	0	0.002	-10000	0	-0.022	2	2
CD3D	0.033	0.036	0.13	83	-0.034	2	85
CD3E	0.03	0.032	0.13	60	-0.019	5	65
CD3G	0.027	0.031	0.13	55	-0.016	29	84
RASGRP2	0.006	0.012	0.061	4	-0.15	1	5
RASGRP1	0.008	0.088	0.21	26	-0.25	29	55
HLA-A	0.001	0.003	-10000	0	-0.023	2	2
RASSF5	0.021	0.003	-10000	0	-10000	0	0
RAP1A/GTP/RAPL	0.025	0.01	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.024	0.046	0.13	57	-0.12	2	59
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.002	0.024	-10000	0	-0.15	3	3
PRKCA	0	0.041	0.12	24	-0.16	4	28
GRAP2	0.023	0.018	0.12	19	-10000	0	19
mol:IP3	0.022	0.067	0.14	100	-0.19	9	109
EntrezGene:6957	0.001	0.002	-10000	0	-0.022	1	1
TCR/CD3/MHC I/CD8	0.01	0.058	0.14	14	-0.32	4	18
ORAI1	-0.19	0.44	0.49	3	-1	135	138
CSK	0.014	0.069	0.19	17	-0.28	9	26
B7 family/CD28	0.049	0.089	0.25	38	-0.3	5	43
CHUK	0.019	0.006	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	0.016	0.073	0.19	13	-0.29	10	23
PTPN6	0.011	0.07	0.2	21	-0.26	10	31
VAV1	0.014	0.072	0.19	22	-0.28	9	31
Monovalent TCR/CD3	0.018	0.039	0.11	37	-0.16	15	52
CBL	0.021	0.003	-10000	0	-10000	0	0
LCK	0.016	0.08	0.2	34	-0.28	9	43
PAG1	0.013	0.07	0.21	18	-0.28	9	27
RAP1A	0.019	0.007	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	0.016	0.072	0.18	19	-0.28	10	29
CD80	0.026	0.026	0.13	39	-0.015	10	49
CD86	0.025	0.019	0.13	22	-10000	0	22
PDK1/CARD11/BCL10/MALT1	0.005	0.031	0.11	1	-0.18	3	4
HRAS	0.02	0.005	-10000	0	-10000	0	0
GO:0035030	0.015	0.066	0.18	34	-0.27	5	39
CD8A	0.021	0.009	0.13	2	-0.034	2	4
CD8B	0.025	0.018	0.13	19	-0.024	4	23
PTPRC	0.024	0.016	0.13	15	-10000	0	15
PDK1/PKC theta	0.02	0.081	0.22	35	-0.33	4	39
CSK/PAG1	0.013	0.072	0.2	27	-0.27	9	36
SOS1	0.021	0.001	-10000	0	-10000	0	0
peptide-MHC class I	0.024	0.024	0.094	68	-10000	0	68
GRAP2/SLP76	0.031	0.077	0.22	24	-0.3	6	30
STIM1	-0.018	0.14	1.1	6	-1	2	8
RAS family/GTP	0.016	0.049	0.13	33	-0.17	6	39
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	0.015	0.069	0.19	7	-0.26	13	20
mol:DAG	-0.003	0.04	0.1	4	-0.18	9	13
RAP1A/GDP	0.013	0.02	0.07	35	-0.067	1	36
PLCG1	0.02	0.004	-10000	0	-10000	0	0
CD247	0.021	0.005	-10000	0	-0.033	2	2
cytotoxic T cell degranulation	-0.031	0.19	-10000	0	-0.56	68	68
RAP1A/GTP	0.002	0.004	-10000	0	-0.049	2	2
mol:PI-3-4-5-P3	0.02	0.074	0.19	34	-0.34	4	38
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.029	0.078	0.19	47	-0.24	8	55
NRAS	0.019	0.007	-10000	0	-10000	0	0
ZAP70	0.023	0.013	0.12	11	-10000	0	11
GRB2/SOS1	0.03	0.006	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	0.014	0.065	0.2	18	-0.26	6	24
MALT1	0.02	0.004	-10000	0	-10000	0	0
TRAF6	0.021	0.003	-10000	0	-10000	0	0
CD8 heterodimer	0.022	0.052	0.15	6	-0.16	45	51
CARD11	0.018	0.009	0.12	1	-10000	0	1
PRKCB	-0.008	0.04	0.11	14	-0.15	20	34
PRKCE	-0.001	0.04	0.12	23	-0.16	4	27
PRKCQ	0.02	0.082	0.21	38	-0.36	4	42
LCP2	0.021	0.009	0.12	4	-10000	0	4
BCL10	0.019	0.007	-10000	0	-10000	0	0
regulation of survival gene product expression	0.017	0.065	0.17	39	-0.26	4	43
IKK complex	-0.003	0.034	0.11	15	-0.1	3	18
RAS family/GDP	0.001	0.006	-10000	0	-0.038	1	1
MAP3K14	0.012	0.049	0.14	31	-0.19	3	34
PDPK1	0.017	0.068	0.18	39	-0.28	4	43
TCR/CD3/MHC I/CD8/Fyn	0.018	0.077	0.22	6	-0.36	9	15

×

IL2 signaling events mediated by STAT5

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
GAB2	0.021	0.003	-10000	0	-10000	0	0
ELF1	0.035	0.025	0.11	2	-10000	0	2
CCNA2	0.056	0.049	0.12	223	-10000	0	223
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
JAK3	0.02	0.005	-10000	0	-10000	0	0
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
JAK1	0.019	0.007	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.019	0.075	-10000	0	-0.29	12	12
SHC1	0.023	0.016	0.12	16	-10000	0	16
SP1	0.023	0.014	0.11	3	-0.27	1	4
IL2RA	0.014	0.048	0.27	3	-10000	0	3
IL2RB	0.03	0.031	0.12	63	-10000	0	63
SOS1	0.021	0.001	-10000	0	-10000	0	0
IL2RG	0.033	0.033	0.12	78	-10000	0	78
G1/S transition of mitotic cell cycle	0.049	0.09	0.3	17	-0.52	3	20
PTPN11	0.021	0.003	-10000	0	-10000	0	0
CCND2	-0.009	0.028	0.27	3	-0.5	1	4
LCK	0.039	0.042	0.12	129	-10000	0	129
GRB2	0.02	0.004	-10000	0	-10000	0	0
IL2	0.015	0.002	-10000	0	-10000	0	0
CDK6	0.024	0.028	0.12	43	-10000	0	43
CCND3	0.014	0.075	-10000	0	-0.43	1	1

×

Nongenotropic Androgen 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
PTK2	-0.006	0.002	-10000	0	-10000	0	0
GNB1/GNG2	0.064	0.04	-10000	0	-0.11	2	2
regulation of S phase of mitotic cell cycle	0.027	0.018	-10000	0	-0.17	1	1
GNAO1	0.021	0.003	-10000	0	-10000	0	0
HRAS	0.02	0.005	-10000	0	-0.02	2	2
SHBG/T-DHT	0.014	0.003	0.081	1	-10000	0	1
PELP1	0.021	0.003	-10000	0	-0.02	2	2
AKT1	-0.006	0.001	-10000	0	-10000	0	0
MAP2K1	-0.005	0.043	0.17	35	-0.14	6	41
T-DHT/AR	0.052	0.037	0.09	329	-10000	0	329
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	0.003	1	-0.007	7	8
GNAI2	0.021	0.003	-10000	0	-10000	0	0
GNAI3	0.019	0.008	0.12	1	-10000	0	1
GNAI1	0.017	0.008	-10000	0	-10000	0	0
mol:GDP	0.016	0.023	-10000	0	-10000	0	0
cell proliferation	0.006	0.067	0.24	18	-0.36	8	26
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
FOS	0.006	0.089	0.34	4	-0.67	8	12
mol:Ca2+	0	0.01	-10000	0	-0.049	4	4
MAPK3	0.005	0.059	0.19	41	-0.26	7	48
MAPK1	0.006	0.062	0.18	4	-0.35	12	16
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
mol:IP3	0	0	0.002	1	-0.005	7	8
cAMP biosynthetic process	-0.004	0.008	-10000	0	-10000	0	0
GNG2	0.02	0.004	-10000	0	-10000	0	0
potassium channel inhibitor activity	0	0	0.002	1	-0.005	7	8
HRAS/GTP	0.058	0.033	-10000	0	-0.071	4	4
actin cytoskeleton reorganization	0.024	0.015	-10000	0	-10000	0	0
SRC	0.02	0.005	-10000	0	-0.018	1	1
voltage-gated calcium channel activity	0	0	0.002	1	-0.005	7	8
PI3K	0.028	0.005	-10000	0	-10000	0	0
apoptosis	-0.011	0.063	0.39	8	-0.23	10	18
T-DHT/AR/PELP1	0.061	0.035	0.096	325	-10000	0	325
HRAS/GDP	0.03	0.024	0.13	8	-10000	0	8
CREB1	0.011	0.066	0.23	10	-0.42	8	18
RAC1-CDC42/GTP	0.03	0.018	-10000	0	-10000	0	0
AR	0.072	0.052	0.12	329	-0.018	1	330
GNB1	0.019	0.007	-10000	0	-10000	0	0
RAF1	0.008	0.045	0.18	37	-10000	0	37
RAC1-CDC42/GDP	0.036	0.03	0.14	4	-10000	0	4
T-DHT/AR/PELP1/Src	0.068	0.036	-10000	0	-10000	0	0
MAP2K2	-0.006	0.039	0.17	28	-0.14	6	34
T-DHT/AR/PELP1/Src/PI3K	0.028	0.018	-10000	0	-0.17	1	1
GNAZ	0.02	0.004	-10000	0	-10000	0	0
SHBG	0.021	0.005	0.12	1	-10000	0	1
Gi family/GNB1/GNG2/GDP	-0.011	0.09	-10000	0	-0.26	67	67
mol:T-DHT	0	0	-10000	0	-0.002	7	7
RAC1	0.018	0.008	-10000	0	-10000	0	0
GNRH1	-0.006	0.004	0.05	3	-10000	0	3
Gi family/GTP	0	0.036	0.096	3	-0.22	4	7
CDC42	0.019	0.006	-10000	0	-10000	0	0

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.057	0.14	0.46	28	-0.52	1	29
CRP	0.049	0.13	0.48	9	-0.52	1	10
cell cycle arrest	0.054	0.13	0.42	17	-0.58	1	18
TIMP1	0.069	0.13	0.41	23	-0.53	2	25
IL6ST	0.02	0.018	-10000	0	-0.039	35	35
Rac1/GDP	-0.018	0.12	0.19	3	-0.32	50	53
AP1	0.052	0.07	0.29	1	-0.41	3	4
GAB2	0.021	0.003	-10000	0	-10000	0	0
TNFSF11	0.049	0.12	0.41	13	-0.52	1	14
HSP90B1	0.038	0.049	-10000	0	-0.48	2	2
GAB1	0.021	0.003	-10000	0	-10000	0	0
MAPK14	-0.066	0.18	0.31	1	-0.5	77	78
AKT1	0.02	0.037	0.22	1	-0.3	5	6
FOXO1	0.016	0.035	-10000	0	-0.29	4	4
MAP2K6	-0.049	0.14	0.23	3	-0.38	76	79
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
MAP2K4	-0.007	0.12	0.29	16	-0.31	38	54
MITF	-0.03	0.11	0.16	6	-0.34	48	54
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.02	0.004	-10000	0	-10000	0	0
A2M	0.006	0.1	-10000	0	-1.1	5	5
CEBPB	0.022	0.007	0.13	2	-10000	0	2
GRB2/SOS1/GAB family/SHP2	0.013	0.056	-10000	0	-0.35	5	5
STAT3	0.052	0.13	0.43	15	-0.61	1	16
STAT1	0.017	0.033	-10000	0	-0.71	1	1
CEBPD	0.054	0.13	0.44	15	-0.52	1	16
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
PI3K	0.031	0.006	-10000	0	-10000	0	0
JUN	0.019	0.007	-10000	0	-10000	0	0
PIAS3/MITF	-0.001	0.13	0.2	46	-0.31	51	97
MAPK11	-0.065	0.18	0.24	2	-0.49	77	79
STAT3 (dimer)/FOXO1	0.025	0.084	0.31	2	-0.45	1	3
GRB2/SOS1/GAB family	0.005	0.11	-10000	0	-0.28	47	47
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.025	0.1	0.15	2	-0.25	83	85
GRB2	0.02	0.004	-10000	0	-10000	0	0
JAK2	0.02	0.005	-10000	0	-10000	0	0
LBP	0.058	0.12	0.41	26	-0.43	1	27
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
JAK1	0.017	0.015	-10000	0	-0.038	27	27
MYC	0.071	0.14	0.44	21	-0.49	1	22
FGG	0.049	0.12	0.42	12	-0.52	1	13
macrophage differentiation	0.054	0.13	0.42	17	-0.58	1	18
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0.016	0.076	0.18	4	-0.18	24	28
JUNB	0.052	0.13	0.44	25	-0.94	1	26
FOS	0.021	0.013	0.12	8	-10000	0	8
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.027	0.12	0.18	4	-0.33	57	61
STAT1/PIAS1	0.003	0.1	0.21	3	-0.26	43	46
GRB2/SOS1/GAB family/SHP2/PI3K	0.026	0.036	-10000	0	-0.29	7	7
STAT3 (dimer)	0.053	0.13	0.43	15	-0.6	1	16
PRKCD	0.044	0.17	0.34	101	-0.43	10	111
IL6R	0.018	0.016	-10000	0	-0.039	32	32
SOCS3	-0.089	0.3	0.45	1	-1	55	56
gp130 (dimer)/JAK1/JAK1/LMO4	0.036	0.041	-10000	0	-0.12	14	14
Rac1/GTP	-0.014	0.11	0.2	4	-0.31	49	53
HCK	0.022	0.014	0.12	11	-10000	0	11
MAPKKK cascade	0.032	0.064	-10000	0	-0.46	3	3
bone resorption	0.05	0.12	0.41	13	-0.5	1	14
IRF1	0.052	0.13	0.44	15	-0.52	1	16
mol:GDP	-0.029	0.11	0.17	5	-0.33	50	55
SOS1	0.021	0.002	-10000	0	-10000	0	0
VAV1	-0.03	0.11	0.17	5	-0.33	50	55
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.073	0.23	-10000	0	-0.52	105	105
PTPN11	0.009	0.074	-10000	0	-0.69	7	7
IL6/IL6RA	-0.001	0.072	0.13	13	-0.16	98	111
gp130 (dimer)/TYK2/TYK2/LMO4	0.033	0.036	-10000	0	-0.12	14	14
gp130 (dimer)/JAK2/JAK2/LMO4	0.031	0.036	-10000	0	-0.12	14	14
IL6	0.017	0.024	0.14	14	-0.039	19	33
PIAS3	0.02	0.005	-10000	0	-10000	0	0
PTPRE	0.005	0.021	-10000	0	-0.042	6	6
PIAS1	0.021	0.003	-10000	0	-10000	0	0
RAC1	0.018	0.008	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.02	0.087	-10000	0	-0.2	105	105
LMO4	0.019	0.017	-10000	0	-0.039	32	32
STAT3 (dimer)/PIAS3	0.024	0.1	0.36	1	-0.59	1	2
MCL1	0.02	0.043	-10000	0	-10000	0	0

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.034	0.021	0.16	1	-10000	0	1
RGS9BP	0.019	0.006	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GRK1	0.02	0.006	0.12	1	-10000	0	1
mol:Na +	0.047	0.034	0.093	217	-0.13	2	219
mol:ADP	-0.011	0.009	0.05	13	-10000	0	13
GNAT2	0.018	0.008	0.12	1	-10000	0	1
RGS9-1/Gbeta5/R9AP	0.04	0.026	-10000	0	-0.12	4	4
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.023	0.011	0.16	1	-10000	0	1
GRK7	0.022	0.014	0.12	12	-10000	0	12
CNGB3	0.018	0.005	-10000	0	-10000	0	0
Cone Metarhodopsin II/X-Arrestin	0.012	0.001	-10000	0	-10000	0	0
mol:Ca2+	0	0.024	0.19	4	-0.17	2	6
Cone PDE6	0.049	0.033	-10000	0	-0.1	4	4
Cone Metarhodopsin II	0.026	0.011	0.09	13	-10000	0	13
Na + (4 Units)	0.026	0.066	-10000	0	-0.12	96	96
GNAT2/GDP	0.043	0.027	-10000	0	-0.094	4	4
GNB5	0.021	0.003	-10000	0	-10000	0	0
mol:GMP (4 units)	-0.011	0.007	0.055	2	-10000	0	2
Cone Transducin	0.037	0.022	0.17	1	-10000	0	1
SLC24A2	0.016	0.009	-10000	0	-10000	0	0
GNB3/GNGT2	0.034	0.02	0.11	40	-10000	0	40
GNB3	0.023	0.019	0.12	21	-10000	0	21
GNAT2/GTP	0.013	0.006	0.089	1	-10000	0	1
CNGA3	0.056	0.049	0.12	222	-10000	0	222
ARR3	0.016	0.001	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
cGMP/Cone CNG Channel	0.048	0.034	0.094	217	-0.13	2	219
mol:Pi	0.04	0.026	-10000	0	-0.12	4	4
Cone CNG Channel	0.045	0.037	-10000	0	-0.11	2	2
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	0.016	0.009	-10000	0	-10000	0	0
RGS9	0.027	0.026	0.12	43	-10000	0	43
PDE6C	0.017	0.007	0.12	1	-10000	0	1
GNGT2	0.025	0.019	0.12	23	-10000	0	23
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	0.019	0.006	0.12	1	-10000	0	1

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.008	0.074	0.34	29	-10000	0	29
VDR	0.023	0.017	0.12	16	-10000	0	16
FAM120B	0.02	0.005	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.004	0.087	-10000	0	-0.27	47	47
RXRs/LXRs/DNA/Oxysterols	-0.016	0.12	-10000	0	-0.39	47	47
MED1	0.021	0.002	-10000	0	-10000	0	0
mol:9cRA	0	0.013	-10000	0	-0.045	44	44
RARs/THRs/DNA/Src-1	0.008	0.043	-10000	0	-0.16	40	40
RXRs/NUR77	0.038	0.058	-10000	0	-0.12	39	39
RXRs/PPAR	0.004	0.052	-10000	0	-0.18	36	36
NCOR2	0.021	0.002	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.014	0.025	0.089	16	-0.15	11	27
RARs/VDR/DNA/Vit D3	0.047	0.025	0.17	2	-0.11	10	12
RARA	0.021	0.002	-10000	0	-10000	0	0
NCOA1	0.021	0.002	-10000	0	-10000	0	0
VDR/VDR/DNA	0.023	0.017	0.12	16	-10000	0	16
RARs/RARs/DNA/9cRA	0.033	0.019	-10000	0	-10000	0	0
RARG	0.021	0.008	0.12	3	-10000	0	3
RPS6KB1	0.009	0.087	0.55	16	-10000	0	16
RARs/THRs/DNA/SMRT	0.008	0.043	-10000	0	-0.16	39	39
THRA	0.021	0.002	-10000	0	-10000	0	0
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.014	0.025	0.089	16	-0.15	11	27
RXRs/PPAR/9cRA/PGJ2/DNA	0.028	0.062	-10000	0	-0.13	74	74
NR1H4	0.041	0.042	0.12	134	-10000	0	134
RXRs/LXRs/DNA	0.04	0.076	-10000	0	-0.18	43	43
NR1H2	0.018	0.018	-10000	0	-0.052	31	31
NR1H3	0.019	0.021	0.13	3	-0.053	42	45
RXRs/VDR/DNA/Vit D3	0.033	0.057	-10000	0	-0.12	50	50
NR4A1	0.021	0.009	0.12	4	-10000	0	4
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	0.006	0.052	-10000	0	-0.24	7	7
RXRG	0.017	0.02	0.13	1	-0.052	43	44
RXR alpha/CCPG	0.027	0.019	-10000	0	-10000	0	0
RXRA	0.018	0.019	-10000	0	-0.051	45	45
RXRB	0.019	0.02	-10000	0	-0.054	45	45
THRB	0.019	0.006	-10000	0	-10000	0	0
PPARG	0.021	0.006	0.12	2	-10000	0	2
PPARD	0.021	0.002	-10000	0	-10000	0	0
TNF	-0.05	0.22	-10000	0	-0.86	45	45
mol:Oxysterols	0	0.011	-10000	0	-0.04	46	46
cholesterol transport	-0.016	0.12	-10000	0	-0.39	47	47
PPARA	0.02	0.004	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.021	0.002	-10000	0	-10000	0	0
RXRs/NUR77/BCL2	0.002	0.046	-10000	0	-0.16	44	44
SREBF1	-0.018	0.11	-10000	0	-0.43	18	18
RXRs/RXRs/DNA/9cRA	0.028	0.062	-10000	0	-0.13	74	74
ABCA1	-0.013	0.11	0.28	2	-0.43	18	20
RARs/THRs	0.05	0.043	-10000	0	-0.12	38	38
RXRs/FXR	0.049	0.066	0.16	1	-0.12	41	42
BCL2	0.021	0.003	-10000	0	-10000	0	0

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.01	0.015	-10000	0	-0.037	5	5
HSPA8	0.021	0.004	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	0.049	0.028	-10000	0	-0.15	1	1
AKT1	0.023	0.006	-10000	0	-10000	0	0
GSC	0.069	0.094	-10000	0	-10000	0	0
NKX2-5	0	0.006	-10000	0	-0.043	13	13
muscle cell differentiation	-0.062	0.061	0.37	2	-10000	0	2
SMAD2-3/SMAD4/SP1	0.093	0.042	0.21	7	-10000	0	7
SMAD4	0.035	0.016	-10000	0	-10000	0	0
CBFB	0.021	0.006	0.12	2	-10000	0	2
SAP18	0.02	0.005	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.036	0.02	-10000	0	-0.13	2	2
SMAD3/SMAD4/VDR	0.061	0.04	0.18	3	-0.13	2	5
MYC	0.041	0.052	0.12	180	-0.031	74	254
CDKN2B	-0.058	0.16	-10000	0	-0.49	3	3
AP1	0.032	0.024	0.14	2	-0.13	1	3
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.009	0.062	-10000	0	-0.26	21	21
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.015	0.041	0.18	1	-0.36	2	3
SP3	0.021	0.001	-10000	0	-10000	0	0
CREB1	0.021	0.001	-10000	0	-10000	0	0
FOXH1	0.027	0.014	0.14	1	-0.051	3	4
SMAD3/SMAD4/GR	0.053	0.024	0.18	1	-10000	0	1
GATA3	0.039	0.044	0.13	122	-10000	0	122
SKI/SIN3/HDAC complex/NCoR1	-0.013	0.083	-10000	0	-0.27	55	55
MEF2C/TIF2	0.042	0.056	0.2	31	-0.23	13	44
endothelial cell migration	-0.018	0.089	1	4	-10000	0	4
MAX	0.011	0.019	0.071	3	-0.026	132	135
RBBP7	0.021	0.002	-10000	0	-10000	0	0
RBBP4	0.019	0.006	-10000	0	-10000	0	0
RUNX2	0.022	0.012	0.12	9	-10000	0	9
RUNX3	0.025	0.025	0.12	36	-10000	0	36
RUNX1	0.029	0.029	0.12	54	-10000	0	54
CTBP1	0.021	0.003	-10000	0	-10000	0	0
NR3C1	0.011	0.019	0.071	3	-0.026	139	142
VDR	0.023	0.017	0.12	16	-10000	0	16
CDKN1A	0.035	0.045	0.36	1	-10000	0	1
KAT2B	0.02	0.006	0.12	1	-0.029	3	4
SMAD2/SMAD2/SMAD4/FOXH1	0.08	0.04	-10000	0	-10000	0	0
DCP1A	0.021	0.003	-10000	0	-10000	0	0
SKI	0.019	0.007	-10000	0	-10000	0	0
SERPINE1	0.018	0.09	-10000	0	-1	4	4
SMAD3/SMAD4/ATF2	0.058	0.024	-10000	0	-0.12	1	1
SMAD3/SMAD4/ATF3	0.058	0.026	0.17	6	-10000	0	6
SAP30	0.021	0.006	0.12	1	-10000	0	1
Cbp/p300/PIAS3	0.025	0.022	-10000	0	-10000	0	0
JUN	0.018	0.024	0.16	9	-10000	0	9
SMAD3/SMAD4/IRF7	0.059	0.03	0.18	5	-10000	0	5
TFE3	0.025	0.009	-10000	0	-0.073	3	3
COL1A2	0.023	0.029	-10000	0	-10000	0	0
mesenchymal cell differentiation	-0.058	0.026	-10000	0	-0.17	5	5
DLX1	0.014	0.011	0.12	1	-10000	0	1
TCF3	0.021	0.01	0.12	5	-10000	0	5
FOS	0.025	0.014	0.13	8	-10000	0	8
SMAD3/SMAD4/Max	0.052	0.026	0.17	2	-10000	0	2
Cbp/p300/SNIP1	0.034	0.015	-10000	0	-10000	0	0
ZBTB17	0.011	0.018	-10000	0	-0.027	107	107
LAMC1	0.028	0.036	0.13	56	-10000	0	56
TGIF2/HDAC complex/SMAD3/SMAD4	0.058	0.028	0.17	2	-10000	0	2
IRF7	0.024	0.02	0.13	22	-10000	0	22
ESR1	0.011	0.021	-10000	0	-0.038	94	94
HNF4A	0.017	0.007	0.12	1	-10000	0	1
MEF2C	0.036	0.062	0.2	47	-0.24	13	60
SMAD2-3/SMAD4	0.071	0.028	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.035	0.012	-10000	0	-10000	0	0
IGHV3OR16-13	0.01	0.014	-10000	0	-0.35	1	1
TGIF2/HDAC complex	0.023	0.019	0.12	21	-10000	0	21
CREBBP	0.015	0.011	-10000	0	-0.033	4	4
SKIL	0.021	0.003	-10000	0	-10000	0	0
HDAC1	0.019	0.006	-10000	0	-10000	0	0
HDAC2	0.02	0.005	-10000	0	-10000	0	0
SNIP1	0.02	0.007	-10000	0	-10000	0	0
GCN5L2	-0.003	0.003	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.069	0.034	0.17	12	-10000	0	12
MSG1/HSC70	0.034	0.018	0.11	12	-0.14	2	14
SMAD2	0.031	0.012	-10000	0	-10000	0	0
SMAD3	0.029	0.012	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.026	0.018	0.15	1	-0.17	1	2
SMAD2/SMAD2/SMAD4	0.011	0.032	0.16	5	-0.16	3	8
NCOR1	0.021	0.002	-10000	0	-10000	0	0
NCOA2	0.02	0.005	-10000	0	-10000	0	0
NCOA1	0.021	0.002	-10000	0	-10000	0	0
MYOD/E2A	0.056	0.039	0.1	246	-10000	0	246
SMAD2-3/SMAD4/SP1/MIZ-1	0.093	0.05	0.22	7	-10000	0	7
IFNB1	0.006	0.023	0.15	6	-10000	0	6
SMAD3/SMAD4/MEF2C	0.07	0.059	0.2	40	-0.23	13	53
CITED1	0.025	0.019	0.12	24	-10000	0	24
SMAD2-3/SMAD4/ARC105	0.079	0.031	-10000	0	-10000	0	0
RBL1	0.023	0.017	0.12	18	-10000	0	18
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.026	0.036	-10000	0	-10000	0	0
RUNX1-3/PEBPB2	0.046	0.032	0.18	13	-10000	0	13
SMAD7	0.037	0.041	-10000	0	-10000	0	0
MYC/MIZ-1	0.033	0.043	-10000	0	-10000	0	0
SMAD3/SMAD4	-0.012	0.056	-10000	0	-0.37	5	5
IL10	0.027	0.04	0.14	46	-10000	0	46
PIASy/HDAC complex	0.023	0.005	-10000	0	-10000	0	0
PIAS3	0.018	0.006	-10000	0	-0.028	2	2
CDK2	0.049	0.049	0.12	198	-0.035	3	201
IL5	0.018	0.028	0.2	6	-10000	0	6
CDK4	0.021	0.029	0.12	42	-0.038	3	45
PIAS4	0.023	0.005	-10000	0	-10000	0	0
ATF3	0.022	0.012	0.12	9	-10000	0	9
SMAD3/SMAD4/SP1	0.071	0.036	0.18	11	-10000	0	11
FOXG1	0.017	0.011	-10000	0	-0.017	46	46
FOXO3	-0.003	0.014	-10000	0	-10000	0	0
FOXO1	-0.003	0.013	-10000	0	-10000	0	0
FOXO4	-0.003	0.014	-10000	0	-10000	0	0
heart looping	0.035	0.061	0.2	47	-0.24	13	60
CEBPB	0.022	0.008	0.12	2	-10000	0	2
SMAD3/SMAD4/DLX1	-0.008	0.092	-10000	0	-0.13	214	214
MYOD1	0.057	0.052	0.12	244	-10000	0	244
SMAD3/SMAD4/HNF4	0.046	0.045	-10000	0	-0.13	29	29
SMAD3/SMAD4/GATA3	0.068	0.05	0.2	36	-10000	0	36
SnoN/SIN3/HDAC complex/NCoR1	0.021	0.003	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.076	0.046	0.21	23	-10000	0	23
SMAD3/SMAD4/SP1-3	0.082	0.036	0.19	4	-10000	0	4
MED15	0.021	0.003	-10000	0	-10000	0	0
SP1	0.027	0.008	-10000	0	-10000	0	0
SIN3B	0.021	0.004	-10000	0	-10000	0	0
SIN3A	0.021	0.003	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.076	0.044	-10000	0	-0.15	4	4
ITGB5	0.017	0.032	0.19	12	-10000	0	12
TGIF/SIN3/HDAC complex/CtBP	0.009	0.052	-10000	0	-0.32	10	10
SMAD3/SMAD4/AR	0.091	0.044	0.16	44	-10000	0	44
AR	0.072	0.052	0.12	329	-10000	0	329
negative regulation of cell growth	0.023	0.036	-10000	0	-0.22	2	2
SMAD3/SMAD4/MYOD	0.081	0.041	0.15	41	-10000	0	41
E2F5	0.023	0.017	0.12	18	-10000	0	18
E2F4	0.021	0.002	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.084	0.044	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4	0.027	0.026	0.19	1	-10000	0	1
TFDP1	0.02	0.004	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.057	0.031	0.21	2	-0.13	1	3
SMAD3/SMAD4/RUNX2	0.059	0.026	0.18	5	-10000	0	5
TGIF2	0.023	0.019	0.12	21	-10000	0	21
TGIF1	0.038	0.039	0.12	111	-10000	0	111
ATF2	0.021	0.001	-10000	0	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	0.011	0.035	-10000	0	-0.3	7	7
Crk/p130 Cas/Paxillin	-0.011	0.059	-10000	0	-0.2	28	28
JUN	-0.01	0.046	-10000	0	-0.25	8	8
HRAS	0.02	0.005	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	0.05	0.058	0.18	17	-0.12	30	47
RAP1A	0.019	0.007	-10000	0	-10000	0	0
FRS2	0.02	0.004	-10000	0	-10000	0	0
RAP1A/GDP	0.014	0.005	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	0.053	0.063	0.18	18	-0.13	41	59
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.021	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.021	0.002	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	0.046	0.048	0.17	14	-0.12	24	38
RHOA	0.021	0.003	-10000	0	-10000	0	0
RAP1A/GTP	0.037	0.053	0.15	8	-0.12	39	47
GRB7	0.02	0.009	0.12	4	-10000	0	4
RET51/GFRalpha1/GDNF	0.052	0.062	0.18	17	-0.13	40	57
MAPKKK cascade	0.015	0.065	-10000	0	-0.18	38	38
BCAR1	0.021	0.003	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	0.046	0.048	0.17	14	-0.12	24	38
lamellipodium assembly	0.002	0.05	-10000	0	-0.19	19	19
RET51/GFRalpha1/GDNF/SHC	0.054	0.062	0.18	17	-0.13	38	55
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	0.046	0.048	0.17	14	-0.12	23	37
RET9/GFRalpha1/GDNF/Shank3	0.042	0.054	0.17	14	-0.14	30	44
MAPK3	-0.015	0.036	0.17	5	-0.2	4	9
DOK1	0.022	0.007	0.12	3	-10000	0	3
DOK6	0.016	0.009	-10000	0	-10000	0	0
PXN	0.021	0.002	-10000	0	-10000	0	0
neurite development	-0.02	0.041	0.15	4	-0.17	29	33
DOK5	0.02	0.004	-10000	0	-10000	0	0
GFRA1	0.021	0.02	0.12	20	-10000	0	20
MAPK8	0.001	0.05	-10000	0	-0.26	8	8
HRAS/GTP	0.035	0.074	-10000	0	-0.17	39	39
tube development	0.041	0.056	0.19	28	-0.13	29	57
MAPK1	-0.015	0.036	0.17	6	-0.2	4	10
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	0.014	0.037	-10000	0	-0.16	23	23
Rac1/GDP	0.013	0.006	-10000	0	-10000	0	0
SRC	0.02	0.004	-10000	0	-10000	0	0
PDLIM7	0.022	0.014	0.12	11	-10000	0	11
RET51/GFRalpha1/GDNF/Dok6	0.036	0.091	0.18	16	-0.14	101	117
SHC1	0.023	0.016	0.12	16	-10000	0	16
RET51/GFRalpha1/GDNF/Dok4	0.052	0.062	0.18	17	-0.13	41	58
RET51/GFRalpha1/GDNF/Dok5	0.053	0.061	0.18	17	-0.13	38	55
PRKCA	0.02	0.004	-10000	0	-10000	0	0
HRAS/GDP	0.015	0.003	-10000	0	-10000	0	0
CREB1	0.011	0.051	0.14	1	-0.21	22	23
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	0.014	0.037	-10000	0	-0.16	23	23
RET51/GFRalpha1/GDNF/Grb7	0.052	0.062	0.18	17	-0.13	41	58
mol:GDP	0	0	-10000	0	-10000	0	0
RET	0.021	0.017	0.12	15	-10000	0	15
DOK4	0.021	0.002	-10000	0	-10000	0	0
JNK cascade	-0.01	0.045	-10000	0	-0.24	8	8
RET9/GFRalpha1/GDNF/FRS2	0.045	0.048	0.17	14	-0.12	23	37
SHANK3	0.02	0.005	-10000	0	-10000	0	0
RASA1	0.021	0.002	-10000	0	-10000	0	0
NCK1	0.021	0.005	0.12	1	-10000	0	1
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	0.015	0.037	-10000	0	-0.16	23	23
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	0.007	0.059	-10000	0	-0.17	56	56
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	0.006	0.063	-10000	0	-0.18	63	63
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	0.012	0.053	-10000	0	-0.18	39	39
PI3K	-0.006	0.083	0.18	1	-0.26	28	29
SOS1	0.021	0.001	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	0.048	0.054	0.17	14	-0.13	29	43
GRB10	0.017	0.008	-10000	0	-10000	0	0
activation of MAPKK activity	0.012	0.044	0.13	4	-0.17	23	27
RET51/GFRalpha1/GDNF/FRS2	0.052	0.062	0.18	17	-0.13	39	56
GAB1	0.021	0.003	-10000	0	-10000	0	0
IRS1	0.021	0.001	-10000	0	-10000	0	0
IRS2	0.02	0.004	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	0.012	0.052	-10000	0	-0.18	39	39
RET51/GFRalpha1/GDNF/PKC alpha	0.051	0.062	0.18	17	-0.13	41	58
GRB2	0.02	0.004	-10000	0	-10000	0	0
PRKACA	0.02	0.004	-10000	0	-10000	0	0
GDNF	0.044	0.044	0.12	155	-10000	0	155
RAC1	0.018	0.008	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	0.053	0.062	0.18	17	-0.13	40	57
Rac1/GTP	0.007	0.06	0.15	1	-0.22	19	20
RET9/GFRalpha1/GDNF	0.036	0.048	0.1	150	-0.13	24	174
GFRalpha1/GDNF	0.039	0.055	0.18	14	-0.16	24	38

×

IL2 signaling events mediated by PI3K

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
BCL2L1	0.014	0.068	0.26	2	-0.3	14	16
UGCG	0.003	0.11	-10000	0	-0.58	20	20
AKT1/mTOR/p70S6K/Hsp90/TERT	0.044	0.082	0.21	7	-0.33	9	16
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.004	0.1	-10000	0	-0.58	20	20
mol:DAG	-0.062	0.24	-10000	0	-0.79	62	62
CaM/Ca2+/Calcineurin A alpha-beta B1	0.042	0.078	0.24	3	-0.33	3	6
FRAP1	0.039	0.084	0.26	3	-0.37	3	6
FOXO3	0.034	0.083	0.23	6	-0.38	3	9
AKT1	0.038	0.086	0.25	4	-0.4	3	7
GAB2	0.022	0.003	-10000	0	-10000	0	0
SMPD1	0.004	0.1	-10000	0	-0.52	22	22
SGMS1	-0.03	0.17	-10000	0	-0.55	61	61
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	-0.004	0.007	-10000	0	-10000	0	0
CALM1	0.02	0.005	-10000	0	-10000	0	0
cell proliferation	0.01	0.12	0.22	15	-0.32	55	70
EIF3A	0.019	0.007	-10000	0	-10000	0	0
PI3K	0.034	0.007	-10000	0	-10000	0	0
RPS6KB1	0.022	0.05	-10000	0	-0.82	2	2
mol:sphingomyelin	-0.062	0.24	-10000	0	-0.79	62	62
natural killer cell activation	0.001	0.001	-10000	0	-10000	0	0
JAK3	0.021	0.006	-10000	0	-10000	0	0
PIK3R1	0.022	0.003	-10000	0	-10000	0	0
JAK1	0.02	0.007	-10000	0	-10000	0	0
NFKB1	0.021	0.002	-10000	0	-10000	0	0
MYC	0.056	0.1	0.3	41	-0.47	1	42
MYB	0.023	0.031	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.032	0.076	0.18	9	-0.26	13	22
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.039	0.051	-10000	0	-0.74	2	2
mol:PI-3-4-5-P3	0.032	0.076	0.18	9	-0.26	13	22
Rac1/GDP	0.015	0.007	-10000	0	-10000	0	0
T cell proliferation	0.028	0.062	0.22	4	-0.25	9	13
SHC1	0.024	0.016	0.13	16	-10000	0	16
RAC1	0.018	0.008	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.003	0.007	0.024	65	-10000	0	65
PRKCZ	0.03	0.057	0.22	4	-0.33	3	7
NF kappa B1 p50/RelA	0.05	0.083	0.25	3	-0.33	3	6
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.018	0.059	0.16	1	-0.3	15	16
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
RELA	0.021	0.003	-10000	0	-10000	0	0
IL2RA	0.04	0.045	0.13	139	-10000	0	139
IL2RB	0.032	0.031	0.13	63	-10000	0	63
TERT	0.059	0.052	0.12	258	-10000	0	258
E2F1	0.026	0.025	-10000	0	-10000	0	0
SOS1	0.022	0.002	-10000	0	-10000	0	0
RPS6	0.021	0.015	0.12	11	-10000	0	11
mol:cAMP	-0.002	0.004	-10000	0	-0.013	64	64
PTPN11	0.022	0.003	-10000	0	-10000	0	0
IL2RG	0.035	0.033	0.13	78	-10000	0	78
actin cytoskeleton organization	0.028	0.062	0.22	4	-0.25	9	13
GRB2	0.021	0.004	-10000	0	-10000	0	0
IL2	0.017	0.003	-10000	0	-10000	0	0
PIK3CA	0.022	0.004	-10000	0	-10000	0	0
Rac1/GTP	0.041	0.022	-10000	0	-10000	0	0
LCK	0.041	0.043	0.13	129	-10000	0	129
BCL2	0.036	0.075	0.34	2	-0.42	1	3

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.005	0.018	-10000	0	-0.036	1	1
AES	0.005	0.018	-10000	0	-10000	0	0
FBXW11	0.021	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
LRP6/FZD1	0.025	0.015	0.11	4	-10000	0	4
SMAD4	0.021	0.003	-10000	0	-10000	0	0
DKK2	0.018	0.012	0.12	5	-10000	0	5
TLE1	0.006	0.018	-10000	0	-0.032	1	1
MACF1	0.019	0.007	-10000	0	-10000	0	0
CTNNB1	0.068	0.11	0.25	96	-0.29	10	106
WIF1	0.007	0.01	-10000	0	-0.015	4	4
beta catenin/RanBP3	0.005	0.064	-10000	0	-0.3	7	7
KREMEN2	0.022	0.009	0.12	5	-10000	0	5
DKK1	0.028	0.031	0.12	60	-10000	0	60
beta catenin/beta TrCP1	0.074	0.1	0.25	92	-0.28	9	101
FZD1	0.018	0.012	0.12	4	-10000	0	4
AXIN2	0.019	0.097	0.6	17	-10000	0	17
AXIN1	0.022	0.002	-10000	0	-10000	0	0
RAN	0.021	0.002	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.02	0.069	-10000	0	-0.62	6	6
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.057	0.08	0.27	15	-0.51	4	19
Axin1/APC/GSK3	0.025	0.069	0.17	36	-0.25	6	42
Axin1/APC/GSK3/beta catenin/Macf1	0.043	0.085	0.21	76	-0.36	5	81
HNF1A	0.006	0.019	-10000	0	-0.033	1	1
CTBP1	0.006	0.019	-10000	0	-0.033	1	1
MYC	0.073	0.17	0.63	54	-10000	0	54
RANBP3	0.02	0.004	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.017	0.061	-10000	0	-0.13	88	88
NKD1	0.037	0.038	0.12	106	-0.016	1	107
TCF4	0.005	0.019	-10000	0	-0.027	6	6
TCF3	0.006	0.021	0.12	5	-10000	0	5
WNT1/LRP6/FZD1/Axin1	0.032	0.045	-10000	0	-0.12	39	39
Ran/GTP	0.015	0.002	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	-0.026	0.058	-10000	0	-0.38	4	4
LEF1	0.008	0.026	0.12	17	-0.033	1	18
DVL1	0.024	0.037	-10000	0	-0.21	1	1
CSNK2A1	0.02	0.004	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.071	0.077	0.28	16	-0.68	2	18
DKK1/LRP6/Kremen 2	0.041	0.033	-10000	0	-0.13	9	9
LRP6	0.021	0.005	-10000	0	-10000	0	0
CSNK1A1	0.006	0.019	-10000	0	-10000	0	0
NLK	0.022	0.002	-10000	0	-10000	0	0
CCND1	0.017	0.076	0.6	9	-10000	0	9
WNT1	0.019	0.008	0.12	1	-0.015	2	3
GSK3A	0.019	0.007	-10000	0	-10000	0	0
GSK3B	0.021	0.003	-10000	0	-10000	0	0
FRAT1	0.019	0.006	-10000	0	-10000	0	0
PPP2R5D	0.023	0.041	-10000	0	-0.27	3	3
APC	0.012	0.081	0.18	118	-0.12	9	127
WNT1/LRP6/FZD1	0.051	0.077	0.14	241	-0.21	6	247
CREBBP	0.006	0.019	-10000	0	-10000	0	0

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	0.016	0.038	-10000	0	-0.15	26	26
epithelial cell differentiation	0.038	0.032	-10000	0	-0.11	24	24
CYFIP2	0.021	0.003	-10000	0	-10000	0	0
ENAH	-0.023	0.042	0.28	6	-10000	0	6
EGFR	0.053	0.054	0.12	235	-10000	0	235
EPHA2	0.02	0.013	0.12	8	-10000	0	8
MYO6	-0.017	0.034	0.17	15	-10000	0	15
CTNNB1	0.021	0.002	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.036	0.019	-10000	0	-0.13	3	3
AQP5	-0.076	0.15	0.21	1	-0.37	134	135
CTNND1	0.021	0.002	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.017	0.032	0.17	13	-10000	0	13
regulation of calcium-dependent cell-cell adhesion	-0.017	0.034	0.17	14	-0.2	2	16
EGF	0.024	0.019	0.12	22	-10000	0	22
NCKAP1	0.021	0.001	-10000	0	-10000	0	0
AQP3	-0.063	0.14	-10000	0	-0.36	107	107
cortical microtubule organization	0.038	0.032	-10000	0	-0.11	24	24
GO:0000145	-0.017	0.03	0.16	13	-10000	0	13
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.043	0.033	-10000	0	-0.11	24	24
MLLT4	0.02	0.005	-10000	0	-10000	0	0
ARF6/GDP	-0.03	0.017	-10000	0	-10000	0	0
ARF6	0.02	0.004	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.048	0.02	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.008	0.026	0.16	3	-0.25	4	7
PVRL2	0.019	0.007	-10000	0	-10000	0	0
ZYX	-0.015	0.028	0.17	7	-10000	0	7
ARF6/GTP	0.051	0.023	-10000	0	-10000	0	0
CDH1	0.022	0.013	0.12	9	-10000	0	9
EGFR/EGFR/EGF/EGF	0.038	0.04	-10000	0	-0.11	19	19
RhoA/GDP	0.039	0.031	-10000	0	-0.11	24	24
actin cytoskeleton organization	-0.016	0.032	0.16	14	-10000	0	14
IGF-1R heterotetramer	0.021	0.003	-10000	0	-10000	0	0
GIT1	0.021	0.002	-10000	0	-10000	0	0
IGF1R	0.021	0.003	-10000	0	-10000	0	0
IGF1	0.021	0.005	0.12	1	-10000	0	1
DIAPH1	-0.013	0.16	-10000	0	-0.46	63	63
Wnt receptor signaling pathway	-0.038	0.032	0.11	24	-10000	0	24
RHOA	0.021	0.003	-10000	0	-10000	0	0
RhoA/GTP	-0.03	0.017	-10000	0	-10000	0	0
CTNNA1	0.021	0.003	-10000	0	-10000	0	0
VCL	-0.017	0.032	0.16	14	-10000	0	14
EFNA1	0.021	0.003	-10000	0	-10000	0	0
LPP	-0.019	0.03	0.16	12	-10000	0	12
Ephrin A1/EPHA2	0.03	0.031	-10000	0	-0.1	23	23
SEC6/SEC8	-0.022	0.02	-10000	0	-0.11	14	14
MGAT3	-0.017	0.034	0.17	14	-0.2	2	16
HGF/MET	-0.026	0.074	-10000	0	-0.12	236	236
HGF	0.018	0.013	0.12	5	-10000	0	5
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.016	0.037	-10000	0	-0.15	26	26
actin cable formation	-0.011	0.059	0.22	15	-0.24	4	19
KIAA1543	-0.017	0.029	0.16	11	-10000	0	11
KIFC3	-0.019	0.03	0.17	10	-10000	0	10
NCK1	0.021	0.005	0.12	1	-10000	0	1
EXOC3	0.021	0.003	-10000	0	-10000	0	0
ACTN1	-0.017	0.032	0.17	13	-10000	0	13
NCK1/GIT1	0.031	0.005	-10000	0	-10000	0	0
mol:GDP	0.038	0.032	-10000	0	-0.11	24	24
EXOC4	0.017	0.009	-10000	0	-10000	0	0
STX4	-0.018	0.033	0.17	14	-10000	0	14
PIP5K1C	-0.017	0.032	0.17	13	-10000	0	13
LIMA1	0.05	0.048	0.12	192	-10000	0	192
ABI1	0.019	0.007	-10000	0	-10000	0	0
ROCK1	-0.022	0.047	0.3	6	-10000	0	6
adherens junction assembly	-0.006	0.044	0.25	9	-0.25	3	12
IGF-1R heterotetramer/IGF1	0.031	0.034	-10000	0	-0.11	31	31
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.026	0.011	-10000	0	-10000	0	0
MET	0.009	0.011	0.12	1	-10000	0	1
PLEKHA7	-0.018	0.031	0.17	11	-10000	0	11
mol:GTP	0.046	0.02	-10000	0	-10000	0	0
establishment of epithelial cell apical/basal polarity	0.016	0.094	0.18	150	-10000	0	150
cortical actin cytoskeleton stabilization	0.016	0.038	-10000	0	-0.15	26	26
regulation of cell-cell adhesion	-0.016	0.032	0.16	14	-10000	0	14
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.016	0.037	-10000	0	-0.15	26	26

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.001	0.061	-10000	0	-0.11	153	153
MAPK9	0.004	0.001	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.004	0.003	-10000	0	-10000	0	0
GNB1/GNG2	0.024	0.013	-10000	0	-0.13	2	2
GNB1	0.019	0.007	-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	0.004	0	-10000	0	-10000	0	0
Gs family/GTP	-0.016	0.052	-10000	0	-0.11	155	155
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	0.009	0.013	0.033	155	-10000	0	155
GNAL	0.016	0.009	-10000	0	-10000	0	0
GNG2	0.02	0.004	-10000	0	-10000	0	0
CRH	0.011	0.01	-10000	0	-10000	0	0
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.002	0.019	-10000	0	-0.21	5	5
MAPK11	0.004	0.008	-10000	0	-0.21	1	1

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.017	0.037	0.18	7	-0.12	2	9
BIRC5	0.078	0.052	0.12	369	-10000	0	369
NFKBIA	-0.006	0.013	0.12	2	-10000	0	2
CPEB1	0.02	0.004	-10000	0	-10000	0	0
AKT1	-0.005	0.02	0.19	4	-10000	0	4
NDEL1	0.021	0.002	-10000	0	-10000	0	0
Aurora A/BRCA1	0.011	0.027	0.12	1	-10000	0	1
NDEL1/TACC3	0.046	0.039	0.16	19	-10000	0	19
GADD45A	0.026	0.028	0.12	46	-10000	0	46
GSK3B	-0.002	0.021	0.07	2	-10000	0	2
PAK1/Aurora A	0.009	0.027	-10000	0	-0.16	4	4
MDM2	0.02	0.004	-10000	0	-10000	0	0
JUB	0	0	-10000	0	-10000	0	0
TPX2	0.004	0.028	0.051	167	-10000	0	167
TP53	0.014	0.032	0.16	4	-0.19	9	13
DLG7	0	0.013	0.12	2	-10000	0	2
AURKAIP1	0.019	0.007	-10000	0	-10000	0	0
ARHGEF7	0.02	0.004	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.039	0.054	0.18	25	-10000	0	25
G2/M transition of mitotic cell cycle	0.011	0.027	0.12	1	-10000	0	1
AURKA	0.005	0.02	0.16	2	-10000	0	2
AURKB	0.049	0.028	0.096	27	-0.091	3	30
CDC25B	0.006	0.014	0.12	2	-0.18	1	3
G2/M transition checkpoint	0.001	0.015	0.093	2	-10000	0	2
mRNA polyadenylation	0.007	0.029	-10000	0	-0.14	7	7
Aurora A/CPEB	0.007	0.029	-10000	0	-0.14	7	7
Aurora A/TACC1/TRAP/chTOG	0.043	0.022	-10000	0	-10000	0	0
BRCA1	0.024	0.017	0.12	18	-10000	0	18
centrosome duplication	0.009	0.027	-10000	0	-0.16	4	4
regulation of centrosome cycle	0.034	0.047	0.15	19	-10000	0	19
spindle assembly	0.042	0.021	-10000	0	-10000	0	0
TDRD7	0.021	0.003	-10000	0	-10000	0	0
Aurora A/RasGAP/Survivin	0.078	0.044	0.17	43	-10000	0	43
CENPA	0.05	0.034	0.12	21	-0.2	2	23
Aurora A/PP2A	0.011	0.027	-10000	0	-10000	0	0
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	0.005	0.023	0.15	2	-10000	0	2
negative regulation of DNA binding	0.014	0.033	0.16	4	-0.19	10	14
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.03	0.006	-10000	0	-10000	0	0
RASA1	0.021	0.002	-10000	0	-10000	0	0
Ajuba/Aurora A	0.001	0.015	0.094	2	-10000	0	2
mitotic prometaphase	-0.012	0.009	0.072	5	-10000	0	5
proteasomal ubiquitin-dependent protein catabolic process	0.005	0.02	0.16	2	-10000	0	2
TACC1	0.021	0.003	-10000	0	-10000	0	0
TACC3	0.046	0.045	0.12	160	-10000	0	160
Aurora A/Antizyme1	0.018	0.032	-10000	0	-10000	0	0
Aurora A/RasGAP	0.011	0.027	-10000	0	-10000	0	0
OAZ1	0.02	0.004	-10000	0	-10000	0	0
RAN	0.021	0.002	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	-0.002	0.021	0.07	2	-10000	0	2
GIT1	0.021	0.002	-10000	0	-10000	0	0
GIT1/beta-PIX/PAK1	-0.003	0.075	-10000	0	-0.13	167	167
Importin alpha/Importin beta/TPX2	0.004	0.028	0.051	167	-10000	0	167
PPP2R5D	0.021	0.002	-10000	0	-10000	0	0
Aurora A/TPX2	0.013	0.032	0.12	11	-10000	0	11
PAK1	0.015	0.009	-10000	0	-10000	0	0
CKAP5	0.021	0.003	-10000	0	-10000	0	0

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.021	0.002	-10000	0	-10000	0	0
LAT2	0.018	0.039	0.17	30	-10000	0	30
AP1	0.031	0.078	0.26	1	-0.32	4	5
mol:PIP3	0.046	0.085	0.23	80	-0.2	1	81
IKBKB	0.01	0.068	0.2	39	-0.16	2	41
AKT1	-0.013	0.058	0.22	31	-10000	0	31
IKBKG	0.008	0.062	0.17	42	-0.17	2	44
MS4A2	0.011	0.012	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
MAP3K1	0.022	0.054	0.23	20	-0.32	1	21
mol:Ca2+	0.042	0.077	0.2	84	-10000	0	84
LYN	0.021	0.009	0.13	3	-10000	0	3
CBLB	0.019	0.03	0.13	22	-0.13	1	23
SHC1	0.023	0.016	0.12	16	-10000	0	16
RasGAP/p62DOK	0.041	0.009	-10000	0	-10000	0	0
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	0.021	0.009	0.12	5	-10000	0	5
PLD2	-0.003	0.044	0.28	11	-10000	0	11
PTPN13	0.025	0.072	-10000	0	-0.62	6	6
PTPN11	0.022	0.007	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	0.011	0.063	0.24	25	-0.3	6	31
SYK	0.022	0.014	0.12	10	-0.019	3	13
GRB2	0.021	0.004	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	0.042	0.041	0.17	25	-0.2	1	26
LAT	0.018	0.032	0.13	22	-0.2	2	24
PAK2	0.026	0.055	0.21	25	-0.28	2	27
NFATC2	0.008	0.037	-10000	0	-0.36	6	6
HRAS	0.028	0.051	0.19	25	-0.27	3	28
GAB2	0.021	0.003	-10000	0	-10000	0	0
PLA2G1B	0.01	0.074	-10000	0	-0.85	4	4
Fc epsilon R1	0.066	0.043	0.17	51	-10000	0	51
Antigen/IgE/Fc epsilon R1	0.063	0.041	0.15	69	-10000	0	69
mol:GDP	0.032	0.045	0.2	13	-0.35	1	14
JUN	0.019	0.007	-10000	0	-10000	0	0
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
FOS	0.021	0.013	0.12	8	-10000	0	8
Antigen/IgE/Fc epsilon R1/LYN/SYK	0.024	0.03	0.16	6	-0.2	2	8
CHUK	0.006	0.059	0.17	39	-0.16	2	41
KLRG1	0.015	0.025	0.25	1	-0.22	1	2
VAV1	0.018	0.03	0.13	21	-0.13	1	22
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	0.019	0.03	0.13	22	-0.13	1	23
negative regulation of mast cell degranulation	0.032	0.038	0.18	24	-0.17	2	26
BTK	0.032	0.038	0.26	1	-0.34	1	2
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	0.032	0.033	0.14	1	-0.2	2	3
GAB2/PI3K/SHP2	-0.013	0.025	-10000	0	-10000	0	0
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	0.023	0.02	0.12	5	-10000	0	5
RAF1	0.009	0.075	-10000	0	-0.93	4	4
Fc epsilon R1/FcgammaRIIB/SHIP	0.098	0.06	0.2	122	-10000	0	122
FCER1G	0.036	0.036	0.13	87	-10000	0	87
FCER1A	0.05	0.048	0.13	184	-0.019	2	186
Antigen/IgE/Fc epsilon R1/Fyn	0.069	0.041	0.17	51	-10000	0	51
MAPK3	0.009	0.073	-10000	0	-0.85	4	4
MAPK1	0.007	0.077	-10000	0	-0.88	4	4
NFKB1	0.021	0.002	-10000	0	-10000	0	0
MAPK8	-0.013	0.16	-10000	0	-0.5	64	64
DUSP1	0.021	0.008	0.12	4	-10000	0	4
NF-kappa-B/RelA	0.009	0.035	0.096	17	-0.11	1	18
actin cytoskeleton reorganization	0.03	0.074	-10000	0	-0.64	6	6
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	0.044	0.044	0.22	10	-0.26	2	12
FER	0.018	0.032	0.13	22	-0.2	2	24
RELA	0.021	0.003	-10000	0	-10000	0	0
ITK	-0.009	0.072	0.087	1	-0.27	47	48
SOS1	0.021	0.001	-10000	0	-10000	0	0
PLCG1	0.04	0.062	0.24	30	-0.32	1	31
cytokine secretion	-0.003	0.022	-10000	0	-0.078	2	2
SPHK1	0.018	0.03	0.13	22	-0.13	1	23
PTK2	0.03	0.078	-10000	0	-0.67	6	6
NTAL/PLCgamma1/GRB2/SLP76/GADs	0.044	0.05	0.22	31	-0.2	1	32
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	0.044	0.079	0.23	62	-0.21	1	63
MAP2K2	0.008	0.078	-10000	0	-0.86	4	4
MAP2K1	0.003	0.071	-10000	0	-0.87	4	4
MAP2K7	0.021	0.003	-10000	0	-10000	0	0
KLRG1/SHP2	0.03	0.037	0.19	23	-0.18	1	24
MAP2K4	0.025	0.072	-10000	0	-1	3	3
Fc epsilon R1/FcgammaRIIB	0.093	0.061	0.2	123	-10000	0	123
mol:Choline	-0.003	0.043	0.28	11	-10000	0	11
SHC/Grb2/SOS1	0.058	0.037	0.19	5	-0.2	1	6
FYN	0.02	0.004	-10000	0	-10000	0	0
DOK1	0.022	0.007	0.12	3	-10000	0	3
PXN	0.027	0.074	0.36	2	-0.62	6	8
HCLS1	0.019	0.03	0.13	22	-0.13	1	23
PRKCB	0.01	0.072	0.19	39	-0.22	2	41
FCGR2B	0.05	0.047	0.12	186	-10000	0	186
IGHE	0	0.004	-10000	0	-10000	0	0
KLRG1/SHIP	0.032	0.039	0.18	24	-0.17	2	26
LCP2	0.022	0.009	0.12	4	-10000	0	4
PLA2G4A	0.019	0.032	0.13	22	-0.2	2	24
RASA1	0.021	0.002	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.003	0.043	0.28	11	-10000	0	11
IKK complex	0.008	0.062	0.19	39	-10000	0	39
WIPF1	0.021	0.004	0.12	1	-10000	0	1

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	-0.037	0.14	-10000	0	-0.28	139	139
CaM/Ca2+	0.015	0.003	-10000	0	-10000	0	0
AKT1	0.02	0.004	-10000	0	-10000	0	0
AKT2	0.019	0.007	-10000	0	-10000	0	0
STXBP4	0.022	0.012	0.12	9	-10000	0	9
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	-0.056	0.14	0.2	1	-0.3	145	146
YWHAZ	0.02	0.005	-10000	0	-10000	0	0
CALM1	0.02	0.005	-10000	0	-10000	0	0
YWHAQ	0.021	0.002	-10000	0	-10000	0	0
TBC1D4	-0.012	0.003	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.02	0.005	-10000	0	-10000	0	0
YWHAB	0.02	0.004	-10000	0	-10000	0	0
SNARE/Synip	0.043	0.011	-10000	0	-10000	0	0
YWHAG	0.017	0.008	-10000	0	-10000	0	0
ASIP	0.055	0.05	0.12	223	-10000	0	223
PRKCI	0.021	0.003	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0.015	0.003	-10000	0	-10000	0	0
RHOQ	0.021	0.001	-10000	0	-10000	0	0
GYS1	0.003	0.001	-10000	0	-10000	0	0
PRKCZ	0.016	0.009	-10000	0	-10000	0	0
TRIP10	0.023	0.016	0.12	15	-10000	0	15
TC10/GTP/CIP4/Exocyst	0.029	0.011	0.096	15	-10000	0	15
AS160/14-3-3	0.008	0.039	-10000	0	-0.28	7	7
VAMP2	0.021	0.002	-10000	0	-10000	0	0
SLC2A4	-0.063	0.16	0.2	1	-0.33	145	146
STX4	0.021	0.002	-10000	0	-10000	0	0
GSK3B	0.011	0.005	-10000	0	-10000	0	0
SFN	0.022	0.02	0.12	23	-10000	0	23
LNPEP	0.021	0.002	-10000	0	-10000	0	0
YWHAE	0.021	0.002	-10000	0	-10000	0	0

×

Caspase cascade in apoptosis

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
TOP1	0.001	0.065	-10000	0	-0.3	17	17
ACTA1	-0.023	0.065	0.18	2	-0.28	23	25
NUMA1	0.002	0.064	0.18	1	-0.28	20	21
SPTAN1	-0.021	0.064	0.18	7	-0.29	20	27
LIMK1	0.004	0.076	0.18	56	-0.3	10	66
BIRC3	0.023	0.017	0.12	16	-10000	0	16
BIRC2	0.021	0.003	-10000	0	-10000	0	0
BAX	0.019	0.007	-10000	0	-10000	0	0
CASP10	-0.009	0.013	0.043	18	-10000	0	18
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.021	0.001	-10000	0	-10000	0	0
PTK2	-0.002	0.069	0.18	1	-0.3	22	23
DIABLO	0.021	0.002	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.02	0.064	0.18	7	-0.29	20	27
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.021	0.002	-10000	0	-10000	0	0
GSN	-0.021	0.064	0.19	5	-0.29	20	25
MADD	0.02	0.004	-10000	0	-10000	0	0
TFAP2A	0.018	0.17	-10000	0	-0.54	53	53
BID	0.002	0.01	-10000	0	-0.11	2	2
MAP3K1	0	0.046	-10000	0	-0.42	5	5
TRADD	0.021	0.002	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.028	0.011	0.11	1	-10000	0	1
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.017	0.069	0.18	16	-0.29	21	37
CASP9	0.019	0.008	0.12	1	-10000	0	1
DNA repair	0.01	0.048	0.19	20	-0.16	1	21
neuron apoptosis	0.017	0.058	-10000	0	-0.64	4	4
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.009	0.068	0.22	3	-0.29	22	25
APAF1	0.021	0.002	-10000	0	-10000	0	0
CASP6	0.014	0.12	-10000	0	-0.83	10	10
TRAF2	0.021	0.003	-10000	0	-10000	0	0
ICAD/CAD	-0.022	0.063	0.26	4	-0.28	21	25
CASP7	-0.027	0.087	0.19	6	-0.23	76	82
KRT18	-0.001	0.1	-10000	0	-0.49	27	27
apoptosis	-0.012	0.076	0.22	2	-0.31	24	26
DFFA	-0.02	0.063	0.2	2	-0.29	21	23
DFFB	-0.02	0.063	0.21	3	-0.29	21	24
PARP1	-0.01	0.048	0.16	1	-0.19	20	21
actin filament polymerization	-0.006	0.074	0.27	10	-0.17	56	66
TNF	0.021	0.015	0.12	11	-10000	0	11
CYCS	0.006	0.028	0.16	2	-0.35	1	3
SATB1	0.011	0.11	-10000	0	-0.78	10	10
SLK	-0.017	0.059	0.21	1	-0.28	21	22
p15 BID/BAX	0.008	0.034	-10000	0	-0.16	18	18
CASP2	0.002	0.048	0.22	7	-0.28	4	11
JNK cascade	0	0.046	0.42	5	-10000	0	5
CASP3	-0.02	0.066	0.18	3	-0.29	23	26
LMNB2	0.035	0.083	0.22	21	-0.36	8	29
RIPK1	0.021	0.003	-10000	0	-10000	0	0
CASP4	0.036	0.037	0.12	96	-10000	0	96
Mammalian IAPs/DIABLO	0.051	0.028	-10000	0	-0.12	13	13
negative regulation of DNA binding	0.018	0.17	-10000	0	-0.53	53	53
stress fiber formation	-0.021	0.059	0.21	1	-0.27	21	22
GZMB	-0.004	0.022	0.062	62	-10000	0	62
CASP1	0.021	0.027	-10000	0	-10000	0	0
LMNB1	0.046	0.096	0.21	71	-0.37	13	84
APP	0.017	0.058	-10000	0	-0.65	4	4
TNFRSF1A	0.021	0.01	0.12	5	-10000	0	5
response to stress	0	0	-10000	0	-10000	0	0
CASP8	-0.004	0.01	0.05	23	-10000	0	23
VIM	-0.009	0.08	0.24	2	-0.32	24	26
LMNA	0.037	0.08	0.22	24	-0.31	8	32
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.004	0.053	-10000	0	-0.27	8	8
LRDD	0	0	-10000	0	-10000	0	0
SREBF1	-0.023	0.063	0.17	2	-0.29	21	23
APAF-1/Caspase 9	-0.04	0.18	-10000	0	-0.6	64	64
nuclear fragmentation during apoptosis	0.002	0.063	0.18	1	-0.28	20	21
CFL2	0.006	0.073	0.18	56	-0.28	10	66
GAS2	-0.022	0.063	0.18	3	-0.28	22	25
positive regulation of apoptosis	0.045	0.089	0.19	90	-0.37	10	100
PRF1	0.025	0.027	0.12	42	-10000	0	42

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.018	0.007	-10000	0	-10000	0	0
PLK4	0.026	0.022	0.12	32	-10000	0	32
regulation of centriole replication	-0.009	0.016	0.051	28	-0.14	3	31

×

Signaling events mediated by PTP1B

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
PDGFRB	0.021	0.008	0.12	4	-10000	0	4
Jak2/Leptin Receptor	0.022	0.094	0.23	6	-0.3	30	36
PTP1B/AKT1	0.043	0.047	0.19	8	-0.51	1	9
FYN	0.02	0.004	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	0.038	0.051	0.19	13	-0.5	1	14
EGFR	0.053	0.055	0.13	235	-10000	0	235
EGF/EGFR	0.051	0.053	0.18	1	-0.42	1	2
CSF1	0.02	0.015	0.12	10	-10000	0	10
AKT1	0.021	0.005	-10000	0	-0.021	2	2
INSR	0.021	0.005	-10000	0	-10000	0	0
PTP1B/N-cadherin	0.046	0.048	0.19	7	-0.48	1	8
Insulin Receptor/Insulin	0.048	0.044	0.2	1	-0.54	1	2
HCK	0.022	0.014	0.12	11	-10000	0	11
CRK	0.021	0.002	-10000	0	-10000	0	0
TYK2	0.038	0.066	0.27	26	-0.47	1	27
EGF	0.028	0.019	0.13	22	-0.028	1	23
YES1	0.02	0.004	-10000	0	-10000	0	0
CAV1	0.064	0.077	0.22	82	-0.52	1	83
TXN	0.023	0.004	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	0.054	0.048	0.2	3	-0.45	1	4
cell migration	-0.038	0.051	0.5	1	-0.19	13	14
STAT3	0.021	0.002	-10000	0	-10000	0	0
PRLR	0.022	0.009	0.12	3	-10000	0	3
ITGA2B	0.022	0.003	-10000	0	-10000	0	0
CSF1R	0.021	0.009	0.12	5	-10000	0	5
Prolactin Receptor/Prolactin	0.029	0.027	-10000	0	-0.16	9	9
FGR	0.02	0.012	0.12	6	-10000	0	6
PTP1B/p130 Cas	0.045	0.048	0.19	8	-0.48	1	9
Crk/p130 Cas	0.055	0.048	0.2	6	-0.46	1	7
DOK1	0.034	0.053	0.21	11	-0.56	1	12
JAK2	0.021	0.098	0.21	4	-0.32	30	34
Jak2/Leptin Receptor/Leptin	0.021	0.061	-10000	0	-0.33	4	4
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
PTPN1	0.038	0.052	0.19	13	-0.5	1	14
LYN	0.021	0.008	0.12	3	-10000	0	3
CDH2	0.021	0.003	-10000	0	-10000	0	0
SRC	0.032	0.043	-10000	0	-0.32	6	6
ITGB3	0.041	0.04	0.12	124	-10000	0	124
CAT1/PTP1B	0.023	0.11	0.28	38	-0.29	24	62
CAPN1	0.022	0.003	-10000	0	-10000	0	0
CSK	0.021	0.003	-10000	0	-10000	0	0
PI3K	0.05	0.043	-10000	0	-0.5	1	1
mol:H2O2	0.001	0.003	-10000	0	-10000	0	0
STAT3 (dimer)	0.018	0.061	-10000	0	-0.35	3	3
negative regulation of transcription	0.021	0.097	0.21	4	-0.32	30	34
FCGR2A	0.033	0.033	0.12	77	-10000	0	77
FER	0.023	0.004	-10000	0	-0.018	1	1
alphaIIb/beta3 Integrin	0.044	0.036	0.11	11	-0.16	7	18
BLK	0.036	0.039	0.12	104	-10000	0	104
Insulin Receptor/Insulin/Shc	0.038	0.016	-10000	0	-10000	0	0
RHOA	0.022	0.004	-10000	0	-10000	0	0
LEPR	0.019	0.01	0.12	3	-10000	0	3
BCAR1	0.021	0.003	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.02	0.004	-10000	0	-10000	0	0
mol:NADPH	0.002	0.003	-10000	0	-10000	0	0
TRPV6	-0.004	0.12	0.22	23	-0.3	46	69
PRL	0.018	0.011	0.13	4	-10000	0	4
SOCS3	-0.076	0.3	-10000	0	-1.1	55	55
SPRY2	0.022	0.005	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.037	0.011	-10000	0	-10000	0	0
CSF1/CSF1R	0.052	0.05	0.2	4	-0.47	1	5
Ras protein signal transduction	-0.003	0.1	0.51	23	-10000	0	23
IRS1	0.021	0.001	-10000	0	-10000	0	0
INS	0.015	0.008	0.12	1	-0.015	26	27
LEP	0.014	0.009	0.12	1	-0.015	9	10
STAT5B	0.036	0.064	0.2	8	-0.33	5	13
STAT5A	0.036	0.064	0.2	8	-0.36	4	12
GRB2	0.02	0.004	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.047	0.048	0.19	7	-0.47	1	8
CSN2	-0.013	0.041	-10000	0	-10000	0	0
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
LAT	0.039	0.043	-10000	0	-0.34	4	4
YBX1	0.024	0.015	0.13	9	-10000	0	9
LCK	0.039	0.042	0.12	129	-10000	0	129
SHC1	0.023	0.016	0.12	16	-10000	0	16
NOX4	0.057	0.05	0.13	215	-10000	0	215

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	0.013	0.026	0.13	2	-10000	0	2
CRKL	0.021	0.005	0.12	1	-10000	0	1
Rac1/GDP	0.013	0.006	-10000	0	-10000	0	0
DOCK1	0.018	0.007	-10000	0	-10000	0	0
ITGA4	0.036	0.036	0.12	95	-10000	0	95
alpha4/beta7 Integrin/MAdCAM1	0.045	0.056	0.18	3	-0.12	54	57
EPO	0.024	0.03	0.12	50	-10000	0	50
alpha4/beta7 Integrin	0.042	0.029	0.18	4	-10000	0	4
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.021	0.002	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.038	0.031	0.12	78	-10000	0	78
EPO/EPOR (dimer)	0.03	0.025	0.11	48	-10000	0	48
lamellipodium assembly	0.005	0.045	-10000	0	-0.27	9	9
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
PI3K	0.03	0.006	-10000	0	-10000	0	0
ARF6	0.02	0.004	-10000	0	-10000	0	0
JAK2	0.017	0.016	-10000	0	-10000	0	0
PXN	0.021	0.002	-10000	0	-10000	0	0
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
MADCAM1	0.018	0.007	-10000	0	-10000	0	0
cell adhesion	0.043	0.055	0.18	3	-0.12	54	57
CRKL/CBL	0.03	0.007	0.11	1	-10000	0	1
ITGB1	0.021	0.016	0.12	12	-10000	0	12
SRC	0.005	0.03	0.16	12	-10000	0	12
ITGB7	0.022	0.012	0.12	8	-10000	0	8
RAC1	0.018	0.008	-10000	0	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.061	0.052	0.18	42	-10000	0	42
p130Cas/Crk/Dock1	0.008	0.039	0.18	17	-10000	0	17
VCAM1	0.054	0.051	0.12	226	-10000	0	226
RHOA	0.021	0.003	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.056	0.032	0.18	10	-10000	0	10
BCAR1	-0.004	0.033	0.18	18	-10000	0	18
EPOR	0.02	0.004	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.021	0.003	-10000	0	-10000	0	0
GIT1	0.021	0.002	-10000	0	-10000	0	0
Rac1/GTP	0.005	0.045	-10000	0	-0.28	9	9

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0.004	0.033	0.19	3	-0.22	3	6
adherens junction organization	0.001	0.044	0.14	4	-0.2	21	25
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.029	0.05	0.16	58	-0.17	1	59
FMN1	0.002	0.046	0.14	4	-0.2	24	28
mol:IP3	0.005	0.026	-10000	0	-0.2	1	1
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.008	0.044	0.17	1	-0.19	24	25
CTNNB1	0.021	0.003	-10000	0	-10000	0	0
AKT1	0.01	0.034	0.16	2	-0.24	1	3
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.011	0.064	-10000	0	-0.27	24	24
CTNND1	0.021	0.003	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.003	0.042	0.14	4	-0.18	23	27
VASP	0.002	0.041	0.14	4	-0.18	23	27
ZYX	0.001	0.038	0.14	2	-0.19	21	23
JUB	0.005	0.042	0.15	2	-0.18	23	25
EGFR(dimer)	0.036	0.058	0.15	1	-0.18	20	21
E-cadherin/beta catenin-gamma catenin	0.037	0.032	-10000	0	-0.12	24	24
mol:PI-3-4-5-P3	0.03	0.042	0.19	2	-0.25	1	3
PIK3CA	0.021	0.005	-10000	0	-10000	0	0
PI3K	0.031	0.043	0.2	2	-0.25	1	3
FYN	0.001	0.032	0.14	7	-0.22	5	12
mol:Ca2+	0.005	0.026	-10000	0	-0.19	1	1
JUP	0.022	0.006	0.13	2	-10000	0	2
PIK3R1	0.021	0.004	-10000	0	-10000	0	0
mol:DAG	0.005	0.026	-10000	0	-0.2	1	1
CDH1	0.022	0.013	0.12	9	-10000	0	9
RhoA/GDP	0.046	0.063	0.16	124	-0.17	1	125
establishment of polarity of embryonic epithelium	0.002	0.04	0.14	4	-0.18	23	27
SRC	0.02	0.004	-10000	0	-10000	0	0
RAC1	0.018	0.008	-10000	0	-10000	0	0
RHOA	0.021	0.003	-10000	0	-10000	0	0
EGFR	0.053	0.054	0.12	235	-10000	0	235
CASR	-0.007	0.027	0.14	7	-10000	0	7
RhoA/GTP	0.016	0.027	-10000	0	-0.17	1	1
AKT2	0.01	0.031	0.16	2	-0.23	1	3
actin cable formation	-0.003	0.042	0.13	4	-0.2	22	26
apoptosis	-0.007	0.034	0.18	6	-0.18	3	9
CTNNA1	0.021	0.003	-10000	0	-10000	0	0
mol:GDP	0.002	0.027	0.14	2	-0.19	1	3
PIP5K1A	0.003	0.043	0.14	4	-0.19	23	27
PLCG1	0.005	0.026	-10000	0	-0.2	1	1
Rac1/GTP	0.039	0.056	-10000	0	-0.17	20	20
homophilic cell adhesion	0	0.002	-10000	0	-10000	0	0

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.036	0.027	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	0.021	0.005	0.12	1	-10000	0	1
STAT1 (dimer)/Cbp/p300	0.029	0.037	0.21	10	-10000	0	10
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.034	0.019	0.13	1	-10000	0	1
antigen processing and presentation of peptide antigen via MHC class I	-0.053	0.058	-10000	0	-0.14	125	125
CaM/Ca2+	0.037	0.028	-10000	0	-10000	0	0
RAP1A	0.019	0.007	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	-0.011	0.026	0.13	10	-10000	0	10
AKT1	-0.015	0.043	0.17	24	-10000	0	24
MAP2K1	-0.017	0.028	0.15	15	-10000	0	15
MAP3K11	-0.015	0.03	0.17	13	-10000	0	13
IFNGR1	0.02	0.007	0.1	2	-10000	0	2
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.21	0.18	-10000	0	-0.34	410	410
Rap1/GTP	-0.025	0.012	-10000	0	-10000	0	0
CRKL/C3G	0.03	0.007	0.11	1	-10000	0	1
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.046	0.031	-10000	0	-10000	0	0
CEBPB	0.003	0.064	0.38	3	-0.52	3	6
STAT3	0.021	0.002	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.058	0.057	-10000	0	-0.66	2	2
STAT1	-0.016	0.031	0.17	13	-10000	0	13
CALM1	0.02	0.005	-10000	0	-10000	0	0
IFN-gamma (dimer)	0.01	0.018	0.13	5	-10000	0	5
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
STAT1 (dimer)/PIAS1	-0.016	0.036	0.17	16	-10000	0	16
CEBPB/PTGES2/Cbp/p300	0.02	0.04	-10000	0	-0.38	2	2
mol:Ca2+	0.034	0.026	-10000	0	-10000	0	0
MAPK3	-0.001	0.064	0.5	1	-0.68	4	5
STAT1 (dimer)	-0.066	0.076	-10000	0	-0.18	120	120
MAPK1	-0.011	0.1	0.5	1	-0.69	13	14
JAK2	0.02	0.006	0.078	1	-10000	0	1
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
JAK1	0.019	0.007	-10000	0	-10000	0	0
CAMK2D	0.021	0.003	-10000	0	-10000	0	0
DAPK1	0.004	0.05	0.3	6	-0.34	2	8
SMAD7	-0.033	0.031	0.11	3	-0.1	4	7
CBL/CRKL/C3G	0.009	0.038	0.19	13	-10000	0	13
PI3K	0.034	0.03	-10000	0	-10000	0	0
IFNG	0.01	0.018	0.13	5	-10000	0	5
apoptosis	0	0.055	0.29	4	-0.42	5	9
CAMK2G	0.019	0.006	-10000	0	-10000	0	0
STAT3 (dimer)	0.021	0.002	-10000	0	-10000	0	0
CAMK2A	0.006	0.01	-10000	0	-10000	0	0
CAMK2B	0.012	0.01	-10000	0	-10000	0	0
FRAP1	-0.014	0.04	0.16	24	-10000	0	24
PRKCD	-0.016	0.042	0.17	26	-10000	0	26
RAP1B	0.021	0.009	0.12	4	-10000	0	4
negative regulation of cell growth	-0.053	0.058	-10000	0	-0.14	125	125
PTPN2	0.021	0.003	-10000	0	-10000	0	0
EP300	0.021	0.004	-10000	0	-10000	0	0
IRF1	0.002	0.044	0.22	11	-10000	0	11
STAT1 (dimer)/PIASy	-0.022	0.029	0.16	8	-10000	0	8
SOCS1	0.042	0.069	-10000	0	-0.98	2	2
mol:GDP	-0.011	0.031	0.15	11	-10000	0	11
CASP1	-0.027	0.038	0.1	9	-0.1	1	10
PTGES2	0.021	0.003	-10000	0	-10000	0	0
IRF9	0.008	0.026	0.16	5	-0.15	2	7
mol:PI-3-4-5-P3	0.024	0.024	-10000	0	-10000	0	0
RAP1/GDP	0.008	0.029	0.098	2	-10000	0	2
CBL	-0.015	0.03	0.17	13	-10000	0	13
MAP3K1	-0.014	0.027	0.15	12	-10000	0	12
PIAS1	0.021	0.003	-10000	0	-10000	0	0
PIAS4	0.02	0.004	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.053	0.058	-10000	0	-0.14	125	125
PTPN11	-0.013	0.027	0.17	13	-10000	0	13
CREBBP	0.021	0.002	-10000	0	-10000	0	0
RAPGEF1	0.021	0.003	-10000	0	-10000	0	0

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	0.023	0.023	0.12	28	-10000	0	28
oxygen homeostasis	0	0	-10000	0	-10000	0	0
TCEB2	0.021	0.002	-10000	0	-10000	0	0
TCEB1	0.02	0.004	-10000	0	-10000	0	0
HIF1A/p53	0.001	0.077	0.2	2	-0.26	40	42
HIF1A	-0.009	0.055	-10000	0	-0.27	28	28
COPS5	0.021	0.003	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.052	0.024	-10000	0	-10000	0	0
FIH (dimer)	0.019	0.006	-10000	0	-10000	0	0
CDKN2A	0.044	0.05	0.12	182	-10000	0	182
ARNT/IPAS	0.026	0.034	0.11	27	-0.16	15	42
HIF1AN	0.019	0.006	-10000	0	-10000	0	0
GNB2L1	0.023	0.016	0.12	15	-10000	0	15
HIF1A/ARNT	-0.003	0.074	0.16	1	-0.27	38	39
CUL2	0.019	0.007	-10000	0	-10000	0	0
OS9	0.019	0.006	-10000	0	-10000	0	0
RACK1/Elongin B/Elongin C	0.042	0.014	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF1A/Hsp90	-0.002	0.073	0.16	2	-0.27	39	41
PHD1-3/OS9	0.043	0.022	-10000	0	-10000	0	0
HIF1A/RACK1/Elongin B/Elongin C	0.014	0.078	-10000	0	-0.26	40	40
VHL	0.021	0.003	-10000	0	-10000	0	0
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
HIF1A/JAB1	-0.004	0.074	0.16	1	-0.26	40	41
EGLN3	0.02	0.004	-10000	0	-10000	0	0
EGLN2	0.019	0.007	-10000	0	-10000	0	0
EGLN1	0.021	0.002	-10000	0	-10000	0	0
TP53	0.031	0.031	0.12	67	-10000	0	67
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.02	0.052	-10000	0	-0.49	6	6
ARNT	0.021	0.002	-10000	0	-10000	0	0
ARD1A	0	0	-10000	0	-10000	0	0
RBX1	0.02	0.004	-10000	0	-10000	0	0
HIF1A/p19ARF	0.014	0.082	0.27	3	-0.26	40	43

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0.045	0.074	-10000	0	-0.37	15	15
HDAC1	0.006	0.018	-10000	0	-0.024	22	22
AES	0.02	0.004	-10000	0	-0.016	1	1
FBXW11	0.021	0.003	-10000	0	-10000	0	0
DTX1	0.021	0.003	-10000	0	-10000	0	0
LRP6/FZD1	0.025	0.014	0.11	4	-10000	0	4
TLE1	0.02	0.003	-10000	0	-0.02	1	1
AP1	0.002	0.043	-10000	0	-0.19	13	13
NCSTN	0.021	0.002	-10000	0	-10000	0	0
ADAM10	0.021	0.003	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.033	0.03	-10000	0	-0.45	1	1
NICD/RBPSUH	0.024	0.064	-10000	0	-0.37	15	15
WIF1	0.007	0.01	-10000	0	-10000	0	0
NOTCH1	0.012	0.063	-10000	0	-0.39	15	15
PSENEN	0.019	0.006	-10000	0	-10000	0	0
KREMEN2	0.022	0.009	0.12	5	-10000	0	5
DKK1	0.028	0.031	0.12	60	-10000	0	60
beta catenin/beta TrCP1	0.011	0.067	0.24	9	-0.26	2	11
APH1B	0.021	0.003	-10000	0	-10000	0	0
APH1A	0.021	0.002	-10000	0	-10000	0	0
AXIN1	0.011	0.033	0.24	2	-10000	0	2
CtBP/CBP/TCF1/TLE1/AES	-0.006	0.037	-10000	0	-0.2	7	7
PSEN1	0.02	0.004	-10000	0	-10000	0	0
FOS	0.021	0.013	0.12	8	-10000	0	8
JUN	0.019	0.007	-10000	0	-10000	0	0
MAP3K7	0.018	0.007	-10000	0	-0.017	21	21
CTNNB1	0.005	0.067	0.23	13	-0.27	2	15
MAPK3	0.021	0.002	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.017	0.061	-10000	0	-0.13	88	88
HNF1A	0.02	0.003	-10000	0	-0.018	2	2
CTBP1	0.02	0.003	-10000	0	-0.018	2	2
MYC	0.041	0.065	-10000	0	-0.81	2	2
NKD1	0.037	0.038	0.12	106	-10000	0	106
FZD1	0.018	0.012	0.12	4	-10000	0	4
NOTCH1 precursor/Deltex homolog 1	0.024	0.065	-10000	0	-0.38	15	15
apoptosis	0.002	0.043	-10000	0	-0.19	13	13
Delta 1/NOTCHprecursor	0.042	0.073	-10000	0	-0.37	15	15
DLL1	0.048	0.047	0.12	176	-10000	0	176
PPARD	0.022	0.057	-10000	0	-0.8	3	3
Gamma Secretase	0.054	0.023	-10000	0	-10000	0	0
APC	0.009	0.039	0.24	1	-0.31	4	5
DVL1	-0.021	0.065	-10000	0	-0.24	50	50
CSNK2A1	0.021	0.004	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	0.041	0.033	-10000	0	-0.13	9	9
LRP6	0.02	0.004	-10000	0	-10000	0	0
CSNK1A1	0.021	0.003	-10000	0	-10000	0	0
NLK	0.003	0.007	-10000	0	-10000	0	0
CCND1	0.027	0.053	-10000	0	-0.8	2	2
WNT1	0.018	0.008	0.12	1	-10000	0	1
Axin1/APC/beta catenin	0.002	0.072	0.3	5	-0.39	1	6
DKK2	0.019	0.012	0.12	5	-10000	0	5
NOTCH1 precursor/DVL1	-0.012	0.085	-10000	0	-0.42	13	13
GSK3B	0.02	0.003	-10000	0	-10000	0	0
FRAT1	0.019	0.006	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	0.028	0.065	-10000	0	-0.38	15	15
PPP2R5D	-0.005	0.046	-10000	0	-0.31	6	6
MAPK1	0.021	0.003	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.049	0.085	-10000	0	-0.13	322	322
RBPJ	0.021	0.003	-10000	0	-10000	0	0
CREBBP	0.024	0.004	-10000	0	-10000	0	0

×

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.027	0.006	-10000	0	-10000	0	0
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0.021	0.003	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.02	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.021	0.002	-10000	0	-10000	0	0
RAC1-CDC42/GTP/PAK family	-0.07	0.1	-10000	0	-0.18	272	272
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.02	0.004	-10000	0	-10000	0	0
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	0.021	0.003	-10000	0	-10000	0	0
FYN	0.02	0.004	-10000	0	-10000	0	0
MAP3K12	0.021	0.003	-10000	0	-10000	0	0
FGR	0.02	0.012	0.12	6	-10000	0	6
p38 alpha/TAB1	-0.02	0.054	-10000	0	-0.26	14	14
PRKG1	0.019	0.009	0.12	2	-10000	0	2
DUSP8	0.019	0.006	-10000	0	-10000	0	0
PGK/cGMP/p38 alpha	0.004	0.069	0.14	3	-0.25	15	18
apoptosis	-0.019	0.051	-10000	0	-0.25	14	14
RAL/GTP	0.024	0.011	-10000	0	-10000	0	0
LYN	0.021	0.008	0.12	3	-10000	0	3
DUSP1	0.021	0.008	0.12	4	-10000	0	4
PAK1	0.015	0.009	-10000	0	-10000	0	0
SRC	0.02	0.004	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.044	0.022	-10000	0	-10000	0	0
TRAF6	0.021	0.003	-10000	0	-10000	0	0
RAC1	0.018	0.008	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
mol:cGMP	0	0	-10000	0	-10000	0	0
CCM2	0.018	0.008	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0.022	0.012	-10000	0	-10000	0	0
MAPK11	0.004	0.094	0.19	49	-0.3	13	62
BLK	0.036	0.039	0.12	104	-10000	0	104
HCK	0.022	0.014	0.12	11	-10000	0	11
MAP2K3	0.021	0.004	0.12	1	-10000	0	1
DUSP16	0.02	0.004	-10000	0	-10000	0	0
DUSP10	0.021	0.003	-10000	0	-10000	0	0
TRAF6/MEKK3	0.026	0.006	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.011	0.084	0.18	30	-0.29	13	43
positive regulation of innate immune response	0.006	0.11	0.21	47	-0.34	14	61
LCK	0.039	0.042	0.12	129	-10000	0	129
p38alpha-beta/MKP7	0.011	0.1	0.22	44	-0.33	14	58
p38alpha-beta/MKP5	0.011	0.11	0.21	44	-0.33	14	58
PGK/cGMP	0.012	0.02	0.089	2	-0.15	9	11
PAK2	0.02	0.004	-10000	0	-10000	0	0
p38alpha-beta/MKP1	0.011	0.11	0.22	45	-0.33	14	59
CDC42	0.019	0.006	-10000	0	-10000	0	0
RALB	0.021	0.001	-10000	0	-10000	0	0
RALA	0.018	0.008	-10000	0	-10000	0	0
PAK3	0.015	0.01	-10000	0	-10000	0	0

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.029	0.027	0.094	90	-10000	0	90
EPHB2	0.019	0.006	-10000	0	-10000	0	0
Syndecan-2/TACI	0.016	0.007	0.094	3	-10000	0	3
LAMA1	0.025	0.022	0.12	30	-10000	0	30
Syndecan-2/alpha2 ITGB1	0.034	0.035	0.19	2	-0.1	23	25
HRAS	0.02	0.005	-10000	0	-10000	0	0
Syndecan-2/CASK	0.004	0.002	-10000	0	-10000	0	0
ITGA5	0.034	0.036	0.12	89	-10000	0	89
BAX	-0.007	0.004	-10000	0	-10000	0	0
EPB41	0.02	0.013	0.12	8	-10000	0	8
positive regulation of cell-cell adhesion	0.017	0.005	-10000	0	-10000	0	0
LAMA3	0.02	0.006	0.12	1	-10000	0	1
EZR	0.02	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	0.018	0.016	0.12	10	-10000	0	10
Syndecan-2/MMP2	0.034	0.031	0.13	1	-10000	0	1
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.03	0.019	0.11	24	-10000	0	24
dendrite morphogenesis	0.016	0.008	-10000	0	-10000	0	0
Syndecan-2/GM-CSF	0.015	0.004	-10000	0	-10000	0	0
determination of left/right symmetry	0.005	0.002	-10000	0	-10000	0	0
Syndecan-2/PKC delta	0.017	0.017	-10000	0	-0.13	8	8
GNB2L1	0.023	0.016	0.12	15	-10000	0	15
MAPK3	-0.001	0.045	0.18	38	-10000	0	38
MAPK1	-0.002	0.044	0.18	35	-10000	0	35
Syndecan-2/RACK1	0.029	0.014	-10000	0	-10000	0	0
NF1	0.021	0.002	-10000	0	-10000	0	0
FGFR/FGF/Syndecan-2	0.005	0.002	-10000	0	-10000	0	0
ITGA2	0.023	0.016	0.12	15	-10000	0	15
MAPK8	-0.006	0.003	-10000	0	-10000	0	0
Syndecan-2/alpha2/beta1 Integrin	0.04	0.03	0.19	3	-0.11	5	8
Syndecan-2/Kininogen	0.017	0.011	0.094	10	-10000	0	10
ITGB1	0.021	0.016	0.12	12	-10000	0	12
SRC	-0.003	0.04	0.17	32	-10000	0	32
Syndecan-2/CASK/Protein 4.1	0.016	0.01	-10000	0	-10000	0	0
extracellular matrix organization	0.016	0.008	0.093	1	-10000	0	1
actin cytoskeleton reorganization	0.029	0.026	0.094	90	-10000	0	90
Syndecan-2/Caveolin-2/Ras	0.025	0.017	-10000	0	-10000	0	0
Syndecan-2/Laminin alpha3	0.013	0.027	-10000	0	-0.13	22	22
Syndecan-2/RasGAP	0.038	0.016	-10000	0	-10000	0	0
alpha5/beta1 Integrin	0.037	0.031	0.18	10	-10000	0	10
PRKCD	0.02	0.004	-10000	0	-10000	0	0
Syndecan-2 dimer	0.017	0.008	-10000	0	-10000	0	0
GO:0007205	0.001	0	-10000	0	-10000	0	0
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	0.022	0.015	0.17	5	-10000	0	5
RHOA	0.021	0.003	-10000	0	-10000	0	0
SDCBP	0.02	0.004	-10000	0	-10000	0	0
TNFRSF13B	0.018	0.008	0.12	3	-10000	0	3
RASA1	0.021	0.002	-10000	0	-10000	0	0
alpha2/beta1 Integrin	0.03	0.019	0.11	24	-10000	0	24
Syndecan-2/Synbindin	0.018	0.006	-10000	0	-10000	0	0
TGFB1	0.019	0.008	0.12	1	-10000	0	1
CASP3	-0.002	0.045	0.18	34	-0.12	7	41
FN1	0.036	0.036	0.12	94	-10000	0	94
Syndecan-2/IL8	0.008	0.054	0.11	3	-0.13	77	80
SDC2	0.005	0.002	-10000	0	-10000	0	0
KNG1	0.018	0.014	0.12	10	-10000	0	10
Syndecan-2/Neurofibromin	0.018	0.005	-10000	0	-10000	0	0
TRAPPC4	0.021	0.003	-10000	0	-10000	0	0
CSF2	0.015	0.002	-10000	0	-10000	0	0
Syndecan-2/TGFB1	0.017	0.008	0.094	1	-10000	0	1
Syndecan-2/Syntenin/PI-4-5-P2	0.017	0.005	-10000	0	-10000	0	0
Syndecan-2/Ezrin	0.029	0.011	-10000	0	-10000	0	0
PRKACA	0	0.046	0.18	39	-10000	0	39
angiogenesis	0.008	0.054	0.11	3	-0.13	77	80
MMP2	0.044	0.043	0.12	145	-10000	0	145
IL8	0.027	0.032	0.12	60	-10000	0	60
calcineurin-NFAT signaling pathway	0.016	0.007	0.093	3	-10000	0	3

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.005	0.074	0.22	27	-10000	0	27
GNAI2	0.021	0.003	-10000	0	-10000	0	0
S1P/S1P5/G12	0.006	0.048	-10000	0	-0.13	73	73
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.021	0.003	-10000	0	-10000	0	0
RhoA/GTP	-0.004	0.075	-10000	0	-0.22	27	27
negative regulation of cAMP metabolic process	-0.016	0.064	-10000	0	-0.18	72	72
GNAZ	0.02	0.004	-10000	0	-10000	0	0
GNAI3	0.019	0.008	0.12	1	-10000	0	1
GNA12	0.018	0.008	-10000	0	-10000	0	0
S1PR5	0.017	0.008	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.016	0.064	-10000	0	-0.18	72	72
RhoA/GDP	0.015	0.002	-10000	0	-10000	0	0
RHOA	0.021	0.003	-10000	0	-10000	0	0
GNAI1	0.017	0.008	-10000	0	-10000	0	0

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.015	0.034	0.15	20	-10000	0	20
DAPP1	0.007	0.077	0.16	17	-0.28	13	30
Src family/SYK family/BLNK-LAT/BTK-ITK	0.003	0.1	0.24	6	-0.31	32	38
mol:DAG	0.007	0.06	0.17	36	-0.16	4	40
HRAS	0.022	0.007	0.064	1	-10000	0	1
RAP1A	0.02	0.009	-10000	0	-10000	0	0
ARF5/GDP	0.021	0.04	0.18	6	-0.26	5	11
PLCG2	0.022	0.009	0.12	5	-10000	0	5
PLCG1	0.02	0.004	-10000	0	-10000	0	0
ARF5	0.017	0.009	-10000	0	-10000	0	0
mol:GTP	-0.011	0.042	0.18	26	-10000	0	26
ARF1/GTP	-0.007	0.035	0.16	21	-10000	0	21
RHOA	0.021	0.003	-10000	0	-10000	0	0
YES1	0.02	0.004	-10000	0	-10000	0	0
RAP1A/GTP	-0.009	0.039	0.16	30	-10000	0	30
ADAP1	-0.014	0.032	0.18	13	-10000	0	13
ARAP3	-0.011	0.041	0.17	26	-10000	0	26
INPPL1	0.021	0.003	-10000	0	-10000	0	0
PREX1	0.02	0.004	-10000	0	-10000	0	0
ARHGEF6	0.022	0.009	0.12	5	-10000	0	5
ARHGEF7	0.02	0.004	-10000	0	-10000	0	0
ARF1	0.021	0.002	-10000	0	-10000	0	0
NRAS	0.02	0.009	-10000	0	-10000	0	0
FYN	0.02	0.004	-10000	0	-10000	0	0
ARF6	0.02	0.004	-10000	0	-10000	0	0
FGR	0.02	0.012	0.12	6	-10000	0	6
mol:Ca2+	0.003	0.044	0.15	36	-0.099	2	38
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.02	0.004	-10000	0	-10000	0	0
ZAP70	0.023	0.013	0.12	11	-10000	0	11
mol:IP3	0.002	0.053	0.17	36	-0.14	2	38
LYN	0.021	0.008	0.12	3	-10000	0	3
ARF1/GDP	0.034	0.048	0.19	11	-0.24	6	17
RhoA/GDP	0.025	0.043	0.17	33	-0.21	1	34
PDK1/Src/Hsp90	0.039	0.013	-10000	0	-10000	0	0
BLNK	0.019	0.01	0.12	3	-10000	0	3
actin cytoskeleton reorganization	0.023	0.084	0.23	60	-0.37	1	61
SRC	0.02	0.004	-10000	0	-10000	0	0
PLEKHA2	-0.014	0.005	0.02	5	-10000	0	5
RAC1	0.018	0.008	-10000	0	-10000	0	0
PTEN	0.018	0.012	-10000	0	-0.03	14	14
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
ARF6/GTP	-0.014	0.041	0.17	26	-10000	0	26
RhoA/GTP	-0.008	0.047	0.17	36	-10000	0	36
Src family/SYK family/BLNK-LAT	0.001	0.065	-10000	0	-0.25	15	15
BLK	0.036	0.039	0.12	104	-10000	0	104
PDPK1	0.021	0.002	-10000	0	-10000	0	0
CYTH1	-0.014	0.038	0.17	22	-10000	0	22
HCK	0.022	0.014	0.12	11	-10000	0	11
CYTH3	-0.014	0.037	0.18	18	-10000	0	18
CYTH2	-0.013	0.039	0.17	21	-10000	0	21
KRAS	0.021	0.007	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.006	0.038	0.23	4	-0.31	4	8
SGK1	0.004	0.06	0.21	2	-0.33	16	18
INPP5D	0.021	0.009	0.12	5	-10000	0	5
mol:GDP	0.023	0.05	0.18	16	-0.25	6	22
SOS1	0.021	0.001	-10000	0	-10000	0	0
SYK	0.022	0.013	0.12	10	-10000	0	10
ARF6/GDP	0.001	0.053	0.18	35	-0.22	1	36
mol:PI-3-4-5-P3	-0.016	0.022	0.2	5	-10000	0	5
ARAP3/RAP1A/GTP	-0.009	0.039	0.16	30	-10000	0	30
VAV1	0.021	0.007	0.12	2	-10000	0	2
mol:PI-3-4-P2	-0.012	0.006	0.051	5	-10000	0	5
RAS family/GTP/PI3K Class I	0.039	0.051	0.18	72	-10000	0	72
PLEKHA1	-0.013	0.006	0.02	4	-10000	0	4
Rac1/GDP	0.023	0.04	0.19	6	-0.24	6	12
LAT	0.021	0.006	0.12	2	-10000	0	2
Rac1/GTP	0.023	0.037	0.18	1	-0.39	2	3
ITK	-0.013	0.037	0.17	20	-10000	0	20
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.005	0.07	0.21	30	-0.21	4	34
LCK	0.039	0.042	0.12	129	-10000	0	129
BTK	-0.014	0.04	0.17	23	-10000	0	23

×

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	-0.009	0.11	0.23	9	-0.32	44	53
IKBKB	0.031	0.07	0.22	29	-0.3	5	34
AKT1	0.006	0.072	0.24	35	-10000	0	35
IKBKG	0.023	0.06	0.21	16	-0.26	4	20
CALM1	0.004	0.044	0.18	4	-0.24	4	8
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
MAP3K1	0.023	0.086	0.28	13	-0.37	6	19
MAP3K7	0.02	0.004	-10000	0	-10000	0	0
mol:Ca2+	0.006	0.048	0.19	3	-0.25	4	7
DOK1	0.022	0.007	0.12	3	-10000	0	3
AP-1	-0.012	0.078	0.22	5	-0.21	50	55
LYN	0.021	0.008	0.12	3	-10000	0	3
BLNK	0.019	0.01	0.12	3	-10000	0	3
SHC1	0.023	0.016	0.12	16	-10000	0	16
BCR complex	0.033	0.028	0.12	47	-10000	0	47
CD22	0.008	0.017	-10000	0	-10000	0	0
CAMK2G	0.005	0.04	0.18	5	-0.23	4	9
CSNK2A1	0.02	0.004	-10000	0	-10000	0	0
INPP5D	0.021	0.01	0.12	5	-10000	0	5
SHC/GRB2/SOS1	-0.009	0.029	0.098	4	-10000	0	4
GO:0007205	0.006	0.048	0.19	3	-0.26	4	7
SYK	0.022	0.013	0.12	10	-10000	0	10
ELK1	0.003	0.048	0.2	5	-0.25	4	9
NFATC1	0.001	0.053	0.29	6	-0.29	4	10
B-cell antigen/BCR complex	0.033	0.028	0.12	47	-10000	0	47
PAG1/CSK	0.03	0.007	-10000	0	-10000	0	0
NFKBIB	0.02	0.034	0.13	10	-0.13	12	22
HRAS	0.005	0.05	0.21	10	-0.25	3	13
NFKBIA	0.019	0.034	0.13	10	-0.12	12	22
NF-kappa-B/RelA/I kappa B beta	0.022	0.03	0.11	20	-0.09	8	28
RasGAP/Csk	0.073	0.047	0.19	36	-10000	0	36
mol:GDP	0.008	0.048	0.18	3	-0.25	4	7
PTEN	0.018	0.007	-10000	0	-10000	0	0
CD79B	0.025	0.021	0.12	28	-10000	0	28
NF-kappa-B/RelA/I kappa B alpha	0.022	0.03	0.11	20	-0.089	8	28
GRB2	0.02	0.004	-10000	0	-10000	0	0
PI3K/BCAP/CD19	0.002	0.074	0.32	4	-0.41	2	6
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
mol:IP3	0.006	0.043	0.19	2	-0.25	3	5
CSK	0.021	0.003	-10000	0	-10000	0	0
FOS	0	0.047	0.22	4	-0.28	2	6
CHUK	-0.003	0.089	0.25	6	-0.26	42	48
IBTK	0.02	0.004	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	0.041	0.058	0.2	12	-0.25	2	14
PTPN6	0.001	0.015	-10000	0	-10000	0	0
RELA	0.021	0.003	-10000	0	-10000	0	0
BCL2A1	0.017	0.023	0.077	26	-0.071	10	36
VAV2	0.003	0.041	0.2	1	-0.22	2	3
ubiquitin-dependent protein catabolic process	0.02	0.034	0.13	10	-0.13	12	22
BTK	0.022	0.017	-10000	0	-10000	0	0
CD19	0.006	0.035	0.15	2	-0.28	1	3
MAP4K1	0.02	0.011	0.12	5	-10000	0	5
CD72	0.034	0.036	0.12	89	-10000	0	89
PAG1	0.02	0.004	-10000	0	-10000	0	0
MAPK14	0.02	0.079	0.26	14	-0.33	5	19
SH3BP5	0.021	0.002	-10000	0	-10000	0	0
PIK3AP1	0.01	0.039	0.18	1	-0.27	4	5
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	0.009	0.075	0.17	1	-0.32	14	15
RAF1	0.002	0.047	0.21	8	-0.27	2	10
RasGAP/p62DOK/SHIP	0.07	0.046	0.18	38	-10000	0	38
CD79A	0.024	0.024	0.12	34	-10000	0	34
re-entry into mitotic cell cycle	-0.012	0.076	0.21	5	-0.21	48	53
RASA1	0.021	0.002	-10000	0	-10000	0	0
MAPK3	-0.003	0.044	0.19	11	-0.3	1	12
MAPK1	-0.002	0.044	0.18	12	-0.29	1	13
CD72/SHP1	0.006	0.071	0.24	17	-0.2	2	19
NFKB1	0.021	0.002	-10000	0	-10000	0	0
MAPK8	0.019	0.08	0.26	15	-0.32	6	21
actin cytoskeleton organization	0.022	0.07	0.25	22	-0.24	1	23
NF-kappa-B/RelA	0.043	0.06	0.22	14	-0.2	10	24
Calcineurin	0.025	0.048	-10000	0	-0.22	4	4
PI3K	-0.009	0.05	-10000	0	-0.18	1	1
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	0.018	0.033	0.19	1	-0.3	3	4
SOS1	0.021	0.001	-10000	0	-10000	0	0
Bam32/HPK1	0.027	0.095	-10000	0	-0.64	11	11
DAPP1	0.011	0.1	-10000	0	-0.76	9	9
cytokine secretion	0.002	0.051	0.26	7	-0.27	4	11
mol:DAG	0.006	0.043	0.19	2	-0.25	3	5
PLCG2	0.022	0.009	0.12	5	-10000	0	5
MAP2K1	0	0.046	0.2	10	-0.33	1	11
B-cell antigen/BCR complex/FcgammaRIIB	0.06	0.047	0.19	36	-10000	0	36
mol:PI-3-4-5-P3	-0.018	0.04	0.14	7	-10000	0	7
ETS1	0.002	0.049	0.19	16	-0.25	2	18
B-cell antigen/BCR complex/LYN/SYK/BLNK	0.053	0.039	0.2	13	-0.1	2	15
B-cell antigen/BCR complex/LYN	0.014	0.036	-10000	0	-0.3	1	1
MALT1	0.02	0.004	-10000	0	-10000	0	0
TRAF6	0.02	0.003	-10000	0	-10000	0	0
RAC1	0.015	0.06	0.22	14	-0.25	1	15
B-cell antigen/BCR complex/LYN/SYK	0.017	0.074	0.21	20	-10000	0	20
CARD11	0.024	0.07	0.2	68	-0.3	2	70
FCGR2B	0.05	0.047	0.12	186	-10000	0	186
PPP3CA	0.021	0.002	-10000	0	-10000	0	0
BCL10	0.018	0.007	-10000	0	-10000	0	0
IKK complex	0.012	0.039	0.14	24	-0.11	10	34
PTPRC	0.023	0.016	0.12	15	-10000	0	15
PDPK1	-0.012	0.042	0.18	15	-10000	0	15
PPP3CB	0.019	0.006	-10000	0	-10000	0	0
PPP3CC	0.02	0.004	-10000	0	-10000	0	0
POU2F2	0.017	0.023	0.12	18	-0.068	3	21

×

VEGFR1 specific signals

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.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.02	0.007	-10000	0	-9999	0
VEGFR1 homodimer/NRP1	-0.007	0.004	-10000	0	-9999	0
mol:DAG	0.008	0.026	0.19	3	-9999	3
VEGFR1 homodimer/NRP1/VEGFR 121	0.025	0.021	-10000	0	-9999	0
CaM/Ca2+	0.012	0.032	0.18	3	-9999	3
HIF1A	0.023	0.009	0.13	3	-9999	3
GAB1	0.021	0.003	-10000	0	-9999	0
AKT1	0.003	0.029	0.16	11	-9999	11
PLCG1	0.008	0.026	0.19	3	-9999	3
NOS3	0.009	0.02	0.2	2	-9999	2
CBL	0.021	0.003	-10000	0	-9999	0
mol:NO	0.02	0.038	0.2	2	-9999	2
FLT1	-0.009	0.005	-10000	0	-9999	0
PGF	0.067	0.053	0.12	298	-9999	298
VEGFR1 homodimer/NRP2/VEGFR121	0.038	0.025	0.18	3	-9999	3
CALM1	0.02	0.005	-10000	0	-9999	0
PIK3CA	0.021	0.003	-10000	0	-9999	0
eNOS/Hsp90	0.037	0.044	0.24	5	-9999	5
endothelial cell proliferation	-0.019	0.053	0.22	2	-9999	2
mol:Ca2+	0.008	0.026	0.19	3	-9999	3
MAPK3	-0.013	0.014	0.17	3	-9999	3
MAPK1	-0.013	0.014	0.17	3	-9999	3
PIK3R1	0.021	0.003	-10000	0	-9999	0
PLGF homodimer	0.067	0.052	0.12	298	-9999	298
PRKACA	0.02	0.004	-10000	0	-9999	0
RP11-342D11.1	0	0	-10000	0	-9999	0
CAV1	0.028	0.035	0.12	73	-9999	73
VEGFA homodimer	0.033	0.034	0.12	79	-9999	79
VEGFR1 homodimer/VEGFA homodimer	0.027	0.024	0.22	1	-9999	1
platelet activating factor biosynthetic process	-0.014	0.021	0.16	8	-9999	8
PI3K	0.068	0.039	0.21	1	-9999	1
PRKCA	-0.003	0.019	0.18	3	-9999	3
PRKCB	-0.002	0.014	0.19	1	-9999	1
VEGFR1 homodimer/PLGF homodimer	0.053	0.04	0.22	1	-9999	1
VEGFA	0.033	0.034	0.12	79	-9999	79
VEGFB	0.021	0.003	-10000	0	-9999	0
mol:IP3	0.008	0.026	0.19	3	-9999	3
RASA1	-0.013	0.016	0.18	4	-9999	4
NRP2	0.022	0.01	0.12	6	-9999	6
VEGFR1 homodimer	-0.009	0.005	-10000	0	-9999	0
VEGFB homodimer	0.021	0.003	-10000	0	-9999	0
NCK1	0.021	0.005	0.12	1	-9999	1
eNOS/Caveolin-1	0.025	0.041	0.19	1	-9999	1
PTPN11	0.021	0.003	-10000	0	-9999	0
mol:PI-3-4-5-P3	0.065	0.038	0.2	1	-9999	1
mol:L-citrulline	0.02	0.038	0.2	2	-9999	2
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.047	0.026	0.21	1	-9999	1
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.037	0.023	-10000	0	-9999	0
CD2AP	0.021	0.002	-10000	0	-9999	0
PI3K/GAB1	0.072	0.04	0.21	1	-9999	1
PDPK1	0.001	0.032	0.17	17	-9999	17
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.037	0.023	-10000	0	-9999	0
mol:NADP	0.02	0.038	0.2	2	-9999	2
HSP90AA1	0.02	0.004	-10000	0	-9999	0
ubiquitin-dependent protein catabolic process	0.046	0.025	0.2	1	-9999	1
VEGFR1 homodimer/NRP2	0.021	0.01	-10000	0	-9999	0

×

Signaling events mediated by PRL

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
CCNE1	0.019	0.007	-10000	0	-10000	0	0
mol:Halofuginone	0.001	0	-10000	0	-10000	0	0
ITGA1	0.031	0.031	0.12	65	-10000	0	65
CDKN1A	-0.012	0.1	-10000	0	-0.32	63	63
PRL-3/alpha Tubulin	0.028	0.01	-10000	0	-10000	0	0
mol:Ca2+	-0.017	0.007	-10000	0	-10000	0	0
AGT	0.021	0.006	0.12	2	-10000	0	2
CCNA2	-0.003	0.044	0.2	25	-10000	0	25
TUBA1B	0.02	0.004	-10000	0	-10000	0	0
EGR1	0.007	0.003	-10000	0	-10000	0	0
CDK2/Cyclin E1	0.028	0.11	0.22	5	-0.28	66	71
MAPK3	-0.012	0.005	0.051	2	-10000	0	2
PRL-2 /Rab GGTase beta	0.028	0.01	-10000	0	-10000	0	0
MAPK1	-0.011	0.005	0.051	2	-10000	0	2
PTP4A1	-0.009	0.003	-10000	0	-10000	0	0
PTP4A3	0.02	0.008	0.12	2	-10000	0	2
PTP4A2	0.019	0.006	-10000	0	-10000	0	0
ITGB1	-0.009	0.01	0.051	12	-10000	0	12
SRC	0.02	0.004	-10000	0	-10000	0	0
RAC1	0.009	0.019	-10000	0	-0.31	2	2
Rab GGTase beta/Rab GGTase alpha	0.027	0.011	-10000	0	-10000	0	0
PRL-1/ATF-5	-0.007	0.039	-10000	0	-10000	0	0
RABGGTA	0.02	0.004	-10000	0	-10000	0	0
BCAR1	-0.018	0.007	-10000	0	-10000	0	0
RHOC	-0.026	0.11	-10000	0	-0.33	76	76
RHOA	0.006	0.04	-10000	0	-0.32	10	10
cell motility	-0.001	0.071	0.27	1	-0.32	12	13
PRL-1/alpha Tubulin	-0.008	0.042	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	0.036	0.025	0.18	1	-10000	0	1
ROCK1	-0.001	0.071	0.27	1	-0.32	12	13
RABGGTB	0.019	0.007	-10000	0	-10000	0	0
CDK2	0.051	0.048	0.12	198	-10000	0	198
mitosis	-0.009	0.003	-10000	0	-10000	0	0
ATF5	0.019	0.007	-10000	0	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	0	0.064	0.21	9	-0.36	15	24
CRKL	0	0.06	-10000	0	-0.38	15	15
HRAS	0.018	0.061	-10000	0	-0.31	15	15
mol:PIP3	0.023	0.084	0.27	12	-0.35	15	27
SPRED1	0.021	0.003	-10000	0	-10000	0	0
SPRED2	0.021	0.002	-10000	0	-10000	0	0
GAB1	0.004	0.063	-10000	0	-0.39	15	15
FOXO3	0.021	0.11	0.27	9	-0.36	24	33
AKT1	0.023	0.11	0.28	6	-0.38	24	30
BAD	0.022	0.11	0.28	8	-0.36	24	32
megakaryocyte differentiation	0.004	0.062	-10000	0	-0.38	15	15
GSK3B	0.021	0.11	0.27	12	-0.36	24	36
RAF1	0.015	0.057	0.23	2	-0.26	14	16
SHC1	0.023	0.016	0.12	16	-10000	0	16
STAT3	0.003	0.063	-10000	0	-0.39	15	15
STAT1	-0.001	0.14	-10000	0	-0.9	14	14
HRAS/SPRED1	0.026	0.06	0.19	1	-0.26	15	16
cell proliferation	0.001	0.062	-10000	0	-0.39	15	15
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
TEC	0.022	0.011	0.12	7	-10000	0	7
RPS6KB1	0.018	0.08	-10000	0	-0.39	14	14
HRAS/SPRED2	0.026	0.061	0.19	1	-0.26	15	16
LYN/TEC/p62DOK	0.036	0.071	-10000	0	-0.38	15	15
MAPK3	0.012	0.057	0.21	15	-0.2	17	32
STAP1	0.005	0.063	-10000	0	-0.39	15	15
GRAP2	0.023	0.018	0.12	19	-10000	0	19
JAK2	-0.003	0.12	-10000	0	-0.78	14	14
STAT1 (dimer)	-0.001	0.14	-10000	0	-0.88	14	14
mol:Gleevec	-0.001	0.003	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	0.05	0.078	-10000	0	-0.36	15	15
actin filament polymerization	-0.001	0.053	-10000	0	-0.33	15	15
LYN	0.021	0.008	0.12	3	-10000	0	3
STAP1/STAT5A (dimer)	-0.003	0.089	-10000	0	-0.54	15	15
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
CBL/CRKL/GRB2	0.021	0.065	-10000	0	-0.36	14	14
PI3K	0.037	0.082	-10000	0	-0.38	13	13
PTEN	0.018	0.007	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	0.014	0.16	-10000	0	-1	14	14
MAPK8	0.001	0.063	-10000	0	-0.4	15	15
STAT3 (dimer)	0.004	0.062	-10000	0	-0.38	15	15
positive regulation of transcription	0.012	0.051	0.19	18	-0.16	14	32
mol:GDP	0.025	0.063	-10000	0	-0.32	15	15
PIK3C2B	0.002	0.063	-10000	0	-0.39	15	15
CBL/CRKL	0.011	0.063	0.21	1	-0.37	14	15
FER	0.004	0.063	-10000	0	-0.39	15	15
SH2B3	0.004	0.063	-10000	0	-0.4	14	14
PDPK1	0.021	0.081	0.27	15	-0.33	14	29
SNAI2	0.003	0.063	-10000	0	-0.39	15	15
positive regulation of cell proliferation	0.001	0.11	-10000	0	-0.68	14	14
KITLG	0.021	0.012	-10000	0	-0.042	14	14
cell motility	0.001	0.11	-10000	0	-0.68	14	14
PTPN6	0.019	0.011	0.12	4	-10000	0	4
EPOR	0.022	0.053	-10000	0	-0.54	2	2
STAT5A (dimer)	0.005	0.093	-10000	0	-0.55	15	15
SOCS1	0.052	0.048	0.12	202	-10000	0	202
cell migration	0.003	0.069	0.44	15	-10000	0	15
SOS1	0.021	0.001	-10000	0	-10000	0	0
EPO	0.024	0.031	0.13	50	-0.029	8	58
VAV1	0.021	0.007	0.12	2	-10000	0	2
GRB10	0	0.055	-10000	0	-0.36	12	12
PTPN11	0.019	0.008	-10000	0	-0.019	25	25
SCF/KIT	0.008	0.066	-10000	0	-0.41	15	15
GO:0007205	0	0.003	-10000	0	-10000	0	0
MAP2K1	0.01	0.05	0.19	5	-0.22	14	19
CBL	0.021	0.003	-10000	0	-10000	0	0
KIT	-0.001	0.17	-10000	0	-1	16	16
MAP2K2	0.012	0.059	0.25	15	-0.22	14	29
SHC/Grb2/SOS1	0.036	0.071	-10000	0	-0.38	15	15
STAT5A	0.007	0.094	-10000	0	-0.56	15	15
GRB2	0.02	0.004	-10000	0	-10000	0	0
response to radiation	0.004	0.062	-10000	0	-0.38	15	15
SHC/GRAP2	0.033	0.019	0.18	2	-10000	0	2
PTPRO	0.004	0.063	-10000	0	-0.39	15	15
SH2B2	-0.001	0.054	-10000	0	-0.35	13	13
DOK1	0.022	0.007	0.12	3	-10000	0	3
MATK	-0.003	0.07	-10000	0	-0.44	15	15
CREBBP	0.024	0.02	-10000	0	-0.11	14	14
BCL2	0.014	0.088	-10000	0	-0.69	4	4

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	0.005	0.052	-10000	0	-0.12	90	90
cell-cell adhesion	0.02	0.017	0.11	9	-10000	0	9
Ephrin B/EPHB2/RasGAP	0.052	0.031	-10000	0	-0.11	10	10
ITSN1	0.021	0.003	-10000	0	-10000	0	0
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
SHC1	0.023	0.016	0.12	16	-10000	0	16
Ephrin B1/EPHB3	0.029	0.01	0.1	9	-10000	0	9
Ephrin B1/EPHB1	0.028	0.017	0.096	12	-0.13	5	17
HRAS/GDP	0.022	0.035	-10000	0	-0.14	15	15
Ephrin B/EPHB1/GRB7	0.056	0.031	-10000	0	-0.11	14	14
Endophilin/SYNJ1	-0.014	0.03	0.17	14	-10000	0	14
KRAS	0.02	0.004	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	0.055	0.031	-10000	0	-0.11	12	12
endothelial cell migration	0.035	0.022	-10000	0	-0.11	1	1
GRB2	0.02	0.004	-10000	0	-10000	0	0
GRB7	0.02	0.009	0.12	4	-10000	0	4
PAK1	-0.015	0.037	0.2	12	-0.2	3	15
HRAS	0.02	0.005	-10000	0	-10000	0	0
RRAS	-0.011	0.034	0.19	14	-10000	0	14
DNM1	0.009	0.01	-10000	0	-10000	0	0
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.016	0.033	0.18	14	-10000	0	14
lamellipodium assembly	-0.02	0.017	-10000	0	-0.11	9	9
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.019	0.03	-10000	0	-0.16	7	7
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
EPHB2	0.019	0.006	-10000	0	-10000	0	0
EPHB3	0.021	0.009	0.12	4	-10000	0	4
EPHB1	0.022	0.011	0.12	7	-10000	0	7
EPHB4	0.019	0.017	0.12	13	-10000	0	13
mol:GDP	-0.006	0.031	0.16	9	-0.15	14	23
Ephrin B/EPHB2	0.041	0.026	-10000	0	-0.11	10	10
Ephrin B/EPHB3	0.045	0.024	-10000	0	-0.11	10	10
JNK cascade	-0.014	0.036	0.21	13	-10000	0	13
Ephrin B/EPHB1	0.045	0.028	-10000	0	-0.11	15	15
RAP1/GDP	0.043	0.078	0.21	98	-0.16	2	100
EFNB2	0.02	0.004	-10000	0	-10000	0	0
EFNB3	0.021	0.003	-10000	0	-10000	0	0
EFNB1	0.022	0.01	0.12	6	-10000	0	6
Ephrin B2/EPHB1-2	0.034	0.021	-10000	0	-0.11	6	6
RAP1B	0.021	0.009	0.12	4	-10000	0	4
RAP1A	0.019	0.007	-10000	0	-10000	0	0
CDC42/GTP	0.025	0.037	-10000	0	-0.16	8	8
Rap1/GTP	-0.026	0.019	-10000	0	-10000	0	0
axon guidance	0.005	0.052	-10000	0	-0.12	90	90
MAPK3	0.004	0.026	-10000	0	-0.15	7	7
MAPK1	0.005	0.024	-10000	0	-0.13	6	6
Rac1/GDP	0.003	0.063	0.21	45	-0.17	2	47
actin cytoskeleton reorganization	-0.021	0.02	-10000	0	-0.13	7	7
CDC42/GDP	0.027	0.088	0.21	115	-0.16	2	117
PI3K	0.039	0.024	-10000	0	-0.11	1	1
EFNA5	0.018	0.007	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.023	0.017	0.096	12	-0.13	1	13
Ephrin B/EPHB2/Intersectin/N-WASP	0.011	0.025	-10000	0	-0.17	10	10
CDC42	0.019	0.006	-10000	0	-10000	0	0
RAS family/GTP	-0.026	0.018	-10000	0	-10000	0	0
PTK2	0.024	0.13	0.54	41	-10000	0	41
MAP4K4	-0.014	0.036	0.21	13	-10000	0	13
SRC	0.02	0.004	-10000	0	-10000	0	0
KALRN	0.02	0.004	-10000	0	-10000	0	0
Intersectin/N-WASP	0.025	0.013	-10000	0	-10000	0	0
neuron projection morphogenesis	0.023	0.11	0.31	82	-0.2	2	84
MAP2K1	0.011	0.027	-10000	0	-0.15	7	7
WASL	0.017	0.008	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	0.047	0.025	-10000	0	-0.12	5	5
cell migration	0.006	0.045	0.17	6	-0.28	2	8
NRAS	0.019	0.007	-10000	0	-10000	0	0
SYNJ1	-0.014	0.03	0.17	14	-10000	0	14
PXN	0.021	0.002	-10000	0	-10000	0	0
TF	-0.017	0.028	0.16	12	-0.2	1	13
HRAS/GTP	0.031	0.029	-10000	0	-0.11	13	13
Ephrin B1/EPHB1-2	0.035	0.021	-10000	0	-0.12	5	5
cell adhesion mediated by integrin	0.009	0.028	0.11	7	-0.14	16	23
RAC1	0.018	0.008	-10000	0	-10000	0	0
mol:GTP	0.035	0.029	-10000	0	-0.11	14	14
RAC1-CDC42/GTP	-0.023	0.018	-10000	0	-0.11	9	9
RASA1	0.021	0.002	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0.022	0.057	0.21	38	-0.16	2	40
ruffle organization	0.036	0.13	0.26	153	-10000	0	153
NCK1	0.021	0.005	0.12	1	-10000	0	1
receptor internalization	-0.01	0.028	0.16	5	-0.19	9	14
Ephrin B/EPHB2/KALRN	0.048	0.037	-10000	0	-0.12	20	20
ROCK1	-0.012	0.006	0.057	2	-10000	0	2
RAS family/GDP	-0.021	0.02	-10000	0	-0.14	8	8
Rac1/GTP	-0.02	0.018	-10000	0	-0.11	8	8
Ephrin B/EPHB1/Src/Paxillin	0.014	0.026	-10000	0	-0.16	13	13

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.042	0.024	-10000	0	-0.11	3	3
ER alpha/Gai/GDP/Gbeta gamma	-0.018	0.1	-10000	0	-0.39	16	16
AKT1	-0.008	0.14	-10000	0	-0.62	31	31
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.005	0.14	-10000	0	-0.63	31	31
mol:Ca2+	0.002	0.015	-10000	0	-0.29	1	1
IGF1R	0.021	0.003	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	0.025	0.018	-10000	0	-0.13	8	8
SHC1	0.023	0.016	0.12	16	-10000	0	16
apoptosis	0.007	0.13	0.59	31	-10000	0	31
RhoA/GTP	-0.017	0.008	-10000	0	-0.11	1	1
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	0.003	0.095	0.19	1	-0.33	15	16
regulation of stress fiber formation	0.008	0.046	-10000	0	-0.15	52	52
E2/ERA-ERB (dimer)	0.028	0.014	0.096	15	-0.13	1	16
KRAS	0.02	0.004	-10000	0	-10000	0	0
G13/GTP	0.025	0.009	-10000	0	-0.11	1	1
pseudopodium formation	-0.008	0.046	0.15	52	-10000	0	52
E2/ER alpha (dimer)/PELP1	0.027	0.009	-10000	0	-0.13	1	1
GRB2	0.02	0.004	-10000	0	-10000	0	0
GNG2	0.02	0.004	-10000	0	-10000	0	0
GNAO1	0.021	0.003	-10000	0	-10000	0	0
HRAS	0.02	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.003	0.1	0.23	2	-0.37	25	27
E2/ER beta (dimer)	0.017	0.012	0.089	15	-10000	0	15
mol:GDP	0.005	0.037	0.15	1	-0.16	23	24
mol:NADP	0.003	0.1	0.23	2	-0.37	25	27
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
mol:IP3	0.002	0.016	-10000	0	-0.3	1	1
IGF-1R heterotetramer	0.021	0.003	-10000	0	-10000	0	0
PLCB1	0.008	0.012	-10000	0	-10000	0	0
PLCB2	0.008	0.012	-10000	0	-10000	0	0
IGF1	0.021	0.005	0.12	1	-10000	0	1
mol:L-citrulline	0.003	0.1	0.23	2	-0.37	25	27
RHOA	0.021	0.003	-10000	0	-10000	0	0
Gai/GDP	0.003	0.11	-10000	0	-0.55	22	22
JNK cascade	0.017	0.012	0.089	15	-10000	0	15
BCAR1	0.021	0.003	-10000	0	-10000	0	0
ESR2	0.023	0.016	0.12	15	-10000	0	15
GNAQ	0.021	0.003	-10000	0	-10000	0	0
ESR1	0.02	0.005	-10000	0	-10000	0	0
Gq family/GDP/Gbeta gamma	-0.003	0.092	-10000	0	-0.44	11	11
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.023	0.054	-10000	0	-1.1	1	1
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	0.005	0.095	0.19	1	-0.33	15	16
GNAZ	0.02	0.004	-10000	0	-10000	0	0
E2/ER alpha (dimer)	0.015	0.007	-10000	0	-0.15	1	1
STRN	0.021	0.003	-10000	0	-10000	0	0
GNAL	0.016	0.009	-10000	0	-10000	0	0
PELP1	0.021	0.002	-10000	0	-10000	0	0
MAPK11	-0.008	0.007	-10000	0	-10000	0	0
GNAI2	0.021	0.003	-10000	0	-10000	0	0
GNAI3	0.019	0.008	0.12	1	-10000	0	1
GNAI1	0.017	0.008	-10000	0	-10000	0	0
HBEGF	0	0.12	0.33	29	-0.37	14	43
cAMP biosynthetic process	-0.006	0.053	-10000	0	-0.1	154	154
SRC	-0.022	0.095	-10000	0	-0.36	17	17
PI3K	0.03	0.006	-10000	0	-10000	0	0
GNB1	0.019	0.007	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	0.026	0.04	-10000	0	-0.14	22	22
SOS1	0.021	0.001	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.015	0.072	-10000	0	-0.27	17	17
Gs family/GTP	-0.002	0.056	-10000	0	-0.1	154	154
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.033	0.016	-10000	0	-10000	0	0
vasodilation	0.004	0.1	0.23	2	-0.35	25	27
mol:DAG	0.002	0.016	-10000	0	-0.3	1	1
Gs family/GDP/Gbeta gamma	-0.013	0.059	-10000	0	-0.18	30	30
MSN	-0.009	0.048	0.15	52	-10000	0	52
Gq family/GTP	0.017	0.013	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.004	0.14	-10000	0	-0.61	31	31
NRAS	0.019	0.007	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.004	0.1	0.35	25	-0.23	2	27
GRB2/SOS1	0.03	0.006	-10000	0	-10000	0	0
RhoA/GDP	0.016	0.043	0.16	1	-0.16	25	26
NOS3	0.003	0.11	0.23	2	-0.39	25	27
GNA11	0.02	0.004	-10000	0	-10000	0	0
MAPKKK cascade	0.001	0.11	-10000	0	-0.4	33	33
E2/ER alpha (dimer)/PELP1/Src	0.006	0.1	0.24	16	-0.34	15	31
ruffle organization	-0.008	0.046	0.15	52	-10000	0	52
ROCK2	-0.006	0.051	0.16	53	-10000	0	53
GNA14	0.021	0.003	-10000	0	-10000	0	0
GNA15	0.021	0.006	0.12	1	-10000	0	1
GNA13	0.02	0.004	-10000	0	-10000	0	0
MMP9	-0.013	0.1	0.36	6	-0.37	14	20
MMP2	-0.01	0.11	0.24	21	-0.37	14	35

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.014	0.013	-10000	0	-0.081	12	12
TRAF2/ASK1	0.027	0.007	-10000	0	-10000	0	0
ATM	0.021	0.003	-10000	0	-10000	0	0
MAP2K3	0.002	0.058	0.2	3	-0.3	6	9
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	-0.004	0.069	0.2	4	-0.27	14	18
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.051	0.048	0.12	196	-10000	0	196
TXN	0.004	0.001	-10000	0	-10000	0	0
CALM1	0.02	0.005	-10000	0	-10000	0	0
GADD45A	0.026	0.028	0.12	46	-10000	0	46
GADD45B	0.022	0.014	0.12	12	-10000	0	12
MAP3K1	0.024	0.018	0.12	21	-10000	0	21
MAP3K6	0.019	0.006	-10000	0	-10000	0	0
MAP3K7	0.02	0.004	-10000	0	-10000	0	0
MAP3K4	0.02	0.005	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.027	0.011	-10000	0	-10000	0	0
TAK1/TAB family	-0.002	0.016	0.11	1	-0.13	3	4
RAC1/OSM/MEKK3	0.033	0.016	-10000	0	-10000	0	0
TRAF2	0.021	0.003	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.002	0.047	-10000	0	-0.27	4	4
TRAF6	0.004	0.001	-10000	0	-10000	0	0
RAC1	0.018	0.008	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	0.012	0.01	-10000	0	-10000	0	0
CCM2	0.018	0.008	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.016	0.065	-10000	0	-0.13	166	166
MAPK11	0.02	0.004	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.006	0.065	-10000	0	-0.12	165	165
OSM/MEKK3	0.025	0.012	-10000	0	-10000	0	0
TAOK1	0.004	0.03	-10000	0	-0.21	13	13
TAOK2	0.009	0.001	-10000	0	-10000	0	0
TAOK3	0.009	0.002	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.021	0.002	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.02	0.005	-10000	0	-10000	0	0
MAP3K10	0.019	0.007	-10000	0	-10000	0	0
MAP3K3	0.021	0.003	-10000	0	-10000	0	0
TRX/ASK1	0.017	0.009	-10000	0	-0.099	3	3
GADD45/MTK1/MTK1	0.058	0.041	0.18	14	-10000	0	14

×

Endothelins

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
AKT1	0.02	0.032	0.13	1	-0.17	6	7
PTK2B	0.021	0.003	-10000	0	-10000	0	0
mol:Ca2+	-0.016	0.14	-10000	0	-0.49	31	31
EDN1	0.033	0.03	0.14	12	-0.13	6	18
EDN3	0.02	0.01	0.12	4	-10000	0	4
EDN2	0.023	0.027	0.12	40	-10000	0	40
HRAS/GDP	-0.009	0.075	0.22	9	-0.35	8	17
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	0.019	0.041	-10000	0	-0.28	4	4
ADCY4	-0.019	0.049	0.19	9	-0.2	3	12
ADCY5	-0.026	0.061	0.19	8	-0.18	46	54
ADCY6	-0.02	0.049	0.18	8	-0.2	3	11
ADCY7	-0.02	0.05	0.19	9	-0.2	3	12
ADCY1	-0.018	0.055	0.19	5	-0.19	42	47
ADCY2	-0.021	0.052	0.19	9	-0.19	11	20
ADCY3	-0.02	0.049	0.19	8	-0.2	3	11
ADCY8	-0.019	0.05	0.21	7	-0.2	2	9
ADCY9	-0.019	0.05	0.19	9	-0.2	3	12
arachidonic acid secretion	-0.011	0.084	0.25	12	-0.35	18	30
ETB receptor/Endothelin-1/Gq/GTP	0.021	0.028	-10000	0	-0.4	1	1
GNAO1	0.021	0.003	-10000	0	-10000	0	0
HRAS	0.02	0.005	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	0.054	0.049	0.19	7	-0.15	5	12
ETA receptor/Endothelin-1/Gs/GTP	0.021	0.073	0.18	7	-0.17	7	14
mol:GTP	0	0.002	-10000	0	-10000	0	0
COL3A1	0.043	0.057	0.18	11	-0.35	2	13
EDNRB	0.034	0.031	0.13	65	-10000	0	65
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	0.02	0.039	0.18	2	-0.31	4	6
CYSLTR1	0.022	0.036	0.17	4	-0.26	2	6
SLC9A1	0.018	0.021	-10000	0	-10000	0	0
mol:GDP	-0.014	0.075	0.22	9	-0.36	9	18
SLC9A3	0.008	0.14	-10000	0	-0.58	21	21
RAF1	-0.018	0.077	0.23	10	-0.35	14	24
JUN	-0.019	0.14	-10000	0	-0.48	35	35
JAK2	0.02	0.031	0.13	1	-0.17	6	7
mol:IP3	0.017	0.042	-10000	0	-0.46	2	2
ETA receptor/Endothelin-1	0.064	0.055	0.23	6	-0.2	6	12
PLCB1	0.019	0.006	-10000	0	-0.017	6	6
PLCB2	0.021	0.008	0.12	2	-0.021	7	9
ETA receptor/Endothelin-3	0.037	0.044	0.15	6	-0.14	16	22
FOS	-0.017	0.11	0.31	10	-0.7	10	20
Gai/GDP	-0.001	0.12	-10000	0	-0.62	22	22
CRK	0.021	0.002	-10000	0	-10000	0	0
mol:Ca ++	0.018	0.043	0.18	1	-0.32	3	4
BCAR1	0.021	0.003	-10000	0	-10000	0	0
PRKCB1	0.015	0.042	-10000	0	-0.36	3	3
GNAQ	0.021	0.006	-10000	0	-0.023	10	10
GNAZ	0.02	0.004	-10000	0	-10000	0	0
GNAL	0.016	0.009	-10000	0	-10000	0	0
Gs family/GDP	-0.031	0.081	-10000	0	-0.31	18	18
ETA receptor/Endothelin-1/Gq/GTP	0.025	0.036	-10000	0	-0.32	2	2
MAPK14	0.011	0.029	0.17	1	-0.19	2	3
TRPC6	-0.017	0.15	-10000	0	-0.52	30	30
GNAI2	0.021	0.003	-10000	0	-10000	0	0
GNAI3	0.019	0.008	0.12	1	-10000	0	1
GNAI1	0.017	0.008	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	0.017	0.037	-10000	0	-0.3	3	3
ETB receptor/Endothelin-2	0.039	0.032	0.12	23	-10000	0	23
ETB receptor/Endothelin-3	0.035	0.037	0.12	4	-0.15	15	19
ETB receptor/Endothelin-1	0.052	0.038	0.18	5	-10000	0	5
MAPK3	-0.016	0.1	0.31	11	-0.6	11	22
MAPK1	-0.018	0.11	0.31	11	-0.6	12	23
Rac1/GDP	-0.008	0.065	0.24	3	-0.36	6	9
cAMP biosynthetic process	-0.043	0.093	0.19	7	-0.25	59	66
MAPK8	-0.023	0.16	-10000	0	-0.5	62	62
SRC	0.02	0.004	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	0.006	0.04	-10000	0	-0.22	8	8
p130Cas/CRK/Src/PYK2	-0.021	0.084	0.3	8	-0.42	9	17
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.008	0.064	0.24	3	-0.36	6	9
COL1A2	0.028	0.043	0.19	2	-10000	0	2
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	0.043	0.039	0.16	13	-10000	0	13
mol:DAG	0.017	0.042	-10000	0	-0.46	2	2
MAP2K2	-0.016	0.096	0.31	18	-0.45	13	31
MAP2K1	-0.02	0.085	0.24	9	-0.45	13	22
EDNRA	0.04	0.041	0.14	68	-0.12	6	74
positive regulation of muscle contraction	0.03	0.079	0.22	85	-0.15	5	90
Gq family/GDP	-0.012	0.071	-10000	0	-0.31	9	9
HRAS/GTP	-0.017	0.072	0.22	9	-0.34	11	20
PRKCH	0.011	0.041	0.2	1	-0.34	3	4
RAC1	0.018	0.008	-10000	0	-10000	0	0
PRKCA	0.015	0.051	0.2	14	-0.34	4	18
PRKCB	-0.005	0.055	0.2	1	-0.34	5	6
PRKCE	0.011	0.041	0.22	1	-0.27	3	4
PRKCD	0.012	0.044	0.21	3	-0.36	3	6
PRKCG	-0.022	0.054	-10000	0	-0.29	7	7
regulation of vascular smooth muscle contraction	-0.02	0.13	0.34	10	-0.95	8	18
PRKCQ	0.016	0.049	0.2	17	-0.37	3	20
PLA2G4A	-0.012	0.089	0.25	11	-0.38	18	29
GNA14	0.021	0.006	-10000	0	-0.023	10	10
GNA15	0.02	0.008	0.12	1	-0.02	10	11
GNA12	0.018	0.008	-10000	0	-10000	0	0
GNA11	0.02	0.006	-10000	0	-0.027	3	3
Rac1/GTP	0.055	0.048	0.21	3	-0.15	5	8
MMP1	-0.009	0.045	0.36	3	-10000	0	3

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.021	0.005	0.12	1	-10000	0	1
Rac1/GDP	0.018	0.01	-10000	0	-0.017	7	7
DOCK1	0.018	0.007	-10000	0	-10000	0	0
ITGA4	0.036	0.036	0.12	95	-10000	0	95
RAC1	0.018	0.008	-10000	0	-10000	0	0
alpha4/beta7 Integrin	0.042	0.029	0.18	4	-10000	0	4
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.021	0.002	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.047	0.031	0.18	10	-10000	0	10
alpha4/beta7 Integrin/Paxillin	0.042	0.029	0.18	7	-10000	0	7
lamellipodium assembly	0.011	0.042	0.25	1	-0.4	4	5
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
PI3K	0.03	0.006	-10000	0	-10000	0	0
ARF6	0.02	0.004	-10000	0	-10000	0	0
TLN1	0.02	0.005	-10000	0	-10000	0	0
PXN	-0.012	0.003	-10000	0	-10000	0	0
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
ARF6/GTP	0.044	0.027	0.14	10	-10000	0	10
cell adhesion	0.045	0.03	0.17	10	-10000	0	10
CRKL/CBL	0.03	0.007	0.11	1	-10000	0	1
alpha4/beta1 Integrin/Paxillin	0.038	0.029	0.17	10	-10000	0	10
ITGB1	0.021	0.016	0.12	12	-10000	0	12
ITGB7	0.022	0.012	0.12	8	-10000	0	8
ARF6/GDP	0.02	0.008	-10000	0	-0.017	8	8
alpha4/beta1 Integrin/Paxillin/VCAM1	0.061	0.051	0.18	45	-10000	0	45
p130Cas/Crk/Dock1	0.037	0.015	-10000	0	-10000	0	0
VCAM1	0.054	0.051	0.12	226	-10000	0	226
alpha4/beta1 Integrin/Paxillin/Talin	0.047	0.031	0.17	10	-10000	0	10
alpha4/beta1 Integrin/Paxillin/GIT1	0.048	0.031	0.17	10	-10000	0	10
BCAR1	0.021	0.003	-10000	0	-10000	0	0
mol:GDP	-0.046	0.03	-10000	0	-0.17	10	10
CBL	0.021	0.003	-10000	0	-10000	0	0
PRKACA	0.02	0.004	-10000	0	-10000	0	0
GIT1	0.021	0.002	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.047	0.031	0.17	10	-10000	0	10
Rac1/GTP	0.012	0.046	0.26	1	-0.44	4	5

×

Calcium signaling in the CD4+ TCR pathway

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
NFATC1	0.001	0.016	-10000	0	-10000	0	0
NFATC2	0.003	0.02	0.07	24	-10000	0	24
NFATC3	0.001	0.016	-10000	0	-10000	0	0
CD40LG	-0.012	0.074	0.2	21	-0.22	4	25
PTGS2	-0.026	0.098	0.2	15	-0.26	79	94
JUNB	0.021	0.006	0.12	1	-10000	0	1
CaM/Ca2+/Calcineurin A alpha-beta B1	0.012	0.014	-10000	0	-10000	0	0
CaM/Ca2+	0.012	0.014	-10000	0	-10000	0	0
CALM1	0.015	0.015	-10000	0	-0.026	3	3
JUN	0.015	0.014	-10000	0	-10000	0	0
mol:Ca2+	-0.001	0.004	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.012	0.007	-10000	0	-10000	0	0
FOSL1	0.04	0.041	0.12	126	-10000	0	126
CREM	0.019	0.007	-10000	0	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	0.024	0.058	0.17	7	-0.17	1	8
FOS	0.017	0.019	0.13	8	-10000	0	8
IFNG	-0.014	0.069	0.18	24	-0.22	4	28
AP-1/NFAT1-c-4	0.032	0.092	0.25	14	-0.24	4	18
FASLG	-0.013	0.073	0.22	13	-0.22	4	17
NFAT1-c-4/ICER1	0.014	0.037	-10000	0	-10000	0	0
IL2RA	-0.002	0.078	0.23	16	-0.22	4	20
FKBP12/FK506	0.015	0.003	-10000	0	-10000	0	0
CSF2	-0.015	0.069	0.24	8	-0.22	4	12
JunB/Fra1/NFAT1-c-4	0.035	0.057	0.19	17	-0.15	1	18
IL4	-0.015	0.069	0.24	8	-0.22	4	12
IL2	-0.002	0.11	-10000	0	-0.86	11	11
IL3	0.015	0.049	-10000	0	-0.59	4	4
FKBP1A	0.02	0.004	-10000	0	-10000	0	0
BATF3	0.022	0.013	0.12	10	-10000	0	10
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.021	0.007	0.12	3	-10000	0	3

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	-0.004	0.075	-10000	0	-0.32	33	33
KLHL20	0.014	0.046	0.15	8	-0.18	7	15
CYFIP2	0.021	0.003	-10000	0	-10000	0	0
Rac1/GDP	0.004	0.052	0.23	5	-0.21	21	26
ENAH	-0.004	0.075	-10000	0	-0.32	33	33
AP1M1	0.02	0.004	-10000	0	-10000	0	0
RAP1B	0.021	0.009	0.12	4	-10000	0	4
RAP1A	0.019	0.007	-10000	0	-10000	0	0
CTNNB1	0.021	0.002	-10000	0	-10000	0	0
CDC42/GTP	0.008	0.03	-10000	0	-0.13	10	10
ABI1/Sra1/Nap1	-0.008	0.02	-10000	0	-0.12	8	8
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.047	0.037	-10000	0	-0.12	24	24
RAPGEF1	-0.007	0.071	0.16	22	-0.3	29	51
CTNND1	0.021	0.002	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.003	0.079	-10000	0	-0.33	34	34
CRK	-0.008	0.069	-10000	0	-0.31	30	30
E-cadherin/gamma catenin/alpha catenin	0.036	0.034	-10000	0	-0.13	24	24
alphaE/beta7 Integrin	0.032	0.011	-10000	0	-10000	0	0
IQGAP1	0.022	0.01	0.12	6	-10000	0	6
NCKAP1	0.021	0.001	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.033	0.017	-10000	0	-10000	0	0
DLG1	-0.004	0.074	-10000	0	-0.33	32	32
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.02	0.018	-10000	0	-0.1	19	19
MLLT4	0.02	0.005	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.038	0.011	-10000	0	-10000	0	0
PI3K	-0.024	0.022	-10000	0	-0.13	15	15
ARF6	0.02	0.004	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
E-cadherin/gamma catenin	0.025	0.036	-10000	0	-0.16	24	24
TIAM1	0.02	0.004	-10000	0	-10000	0	0
E-cadherin(dimer)/Ca2+	0.043	0.033	-10000	0	-0.11	24	24
AKT1	-0.012	0.028	0.079	41	-10000	0	41
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
CDH1	0.022	0.013	0.12	9	-10000	0	9
RhoA/GDP	0.008	0.061	0.22	8	-0.21	24	32
actin cytoskeleton organization	0.015	0.042	0.14	28	-0.13	7	35
CDC42/GDP	0.009	0.06	0.23	7	-0.2	24	31
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.007	0.032	-10000	0	-0.16	24	24
ITGB7	0.022	0.012	0.12	8	-10000	0	8
RAC1	0.018	0.008	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.046	0.036	-10000	0	-0.12	24	24
E-cadherin/Ca2+/beta catenin/alpha catenin	0.032	0.029	-10000	0	-0.11	24	24
mol:GDP	-0.002	0.066	0.23	8	-0.23	24	32
CDC42/GTP/IQGAP1	0.026	0.011	-10000	0	-10000	0	0
JUP	0.021	0.006	0.12	2	-10000	0	2
p120 catenin/RhoA/GDP	0.014	0.061	0.22	5	-0.21	24	29
RAC1/GTP/IQGAP1	0.024	0.012	0.096	5	-10000	0	5
PIP5K1C/AP1M1	0.03	0.01	-10000	0	-0.16	1	1
RHOA	0.021	0.003	-10000	0	-10000	0	0
CDC42	0.019	0.006	-10000	0	-10000	0	0
CTNNA1	0.021	0.003	-10000	0	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.016	0.036	0.12	36	-0.097	2	38
NME1	0.021	0.006	0.12	2	-10000	0	2
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	-0.003	0.075	-10000	0	-0.33	32	32
regulation of cell-cell adhesion	-0.018	0.021	-10000	0	-0.11	12	12
WASF2	0.002	0.02	0.056	21	-0.075	3	24
Rap1/GTP	0.013	0.044	0.16	27	-10000	0	27
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.055	0.038	-10000	0	-0.12	24	24
CCND1	0.018	0.04	0.13	34	-0.12	2	36
VAV2	0.005	0.1	-10000	0	-0.57	10	10
RAP1/GDP	0.014	0.051	0.17	22	-0.17	11	33
adherens junction assembly	-0.003	0.073	-10000	0	-0.32	32	32
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.019	0.007	-10000	0	-10000	0	0
PIP5K1C	0.02	0.004	-10000	0	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.039	0.036	0.17	7	-0.12	24	31
E-cadherin/beta catenin	0	0.046	-10000	0	-0.23	24	24
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	-0.003	0.074	-10000	0	-0.33	31	31
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
Rac1/GTP	0.003	0.049	-10000	0	-0.27	8	8
E-cadherin/beta catenin/alpha catenin	0.036	0.035	-10000	0	-0.13	24	24
ITGAE	0.021	0.007	0.12	3	-10000	0	3
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.003	0.08	-10000	0	-0.34	34	34

×

Regulation of Telomerase

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
Telomerase catalytic core complex	0.064	0.083	-10000	0	-0.42	1	1
RAD9A	0.021	0.003	-10000	0	-10000	0	0
AP1	0.028	0.024	0.11	2	-0.15	7	9
IFNAR2	0.024	0.006	-10000	0	-10000	0	0
AKT1	0.016	0.01	-10000	0	-10000	0	0
ER alpha/Oestrogen	0.017	0.008	-10000	0	-0.15	1	1
NFX1/SIN3/HDAC complex	-0.001	0.065	-10000	0	-0.23	22	22
EGF	0.026	0.019	0.13	22	-10000	0	22
SMG5	0.021	0.003	-10000	0	-10000	0	0
SMG6	0.021	0.002	-10000	0	-10000	0	0
SP3/HDAC2	0.036	0.01	-10000	0	-10000	0	0
TERT/c-Abl	0.067	0.078	-10000	0	-0.42	1	1
SAP18	0.021	0.005	-10000	0	-10000	0	0
MRN complex	0.04	0.012	-10000	0	-10000	0	0
WT1	0.033	0.034	0.13	71	-10000	0	71
WRN	0.021	0.003	-10000	0	-10000	0	0
SP1	0.025	0.006	-10000	0	-10000	0	0
SP3	0.023	0.002	-10000	0	-10000	0	0
TERF2IP	0.021	0.003	-10000	0	-10000	0	0
Telomerase/Nucleolin	0.07	0.07	-10000	0	-0.37	1	1
Mad/Max	0.034	0.009	-10000	0	-10000	0	0
TERT	0.065	0.084	-10000	0	-0.43	1	1
CCND1	0.063	0.082	-10000	0	-10000	0	0
MAX	0.022	0.005	-10000	0	-10000	0	0
RBBP7	0.022	0.002	-10000	0	-10000	0	0
RBBP4	0.019	0.007	-10000	0	-10000	0	0
TERF2	0.017	0.004	0.067	1	-10000	0	1
PTGES3	0.021	0.003	-10000	0	-10000	0	0
SIN3A	0.021	0.003	-10000	0	-10000	0	0
Telomerase/911	0.04	0.044	0.2	1	-0.27	3	4
CDKN1B	0.001	0.017	-10000	0	-10000	0	0
RAD1	0.021	0.002	-10000	0	-10000	0	0
XRCC5	0.021	0.001	-10000	0	-10000	0	0
XRCC6	0.02	0.004	-10000	0	-10000	0	0
SAP30	0.021	0.006	0.13	1	-10000	0	1
TRF2/PARP2	0.028	0.007	-10000	0	-10000	0	0
UBE3A	0.022	0.003	-10000	0	-10000	0	0
JUN	0.02	0.007	-10000	0	-10000	0	0
E6	0.001	0.002	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.019	0.004	-10000	0	-10000	0	0
FOS	0.022	0.013	0.12	8	-10000	0	8
IFN-gamma/IRF1	0.039	0.022	0.17	3	-10000	0	3
PARP2	0.02	0.004	-10000	0	-10000	0	0
BLM	0.03	0.03	0.12	61	-10000	0	61
Telomerase	0.021	0.059	0.19	2	-0.28	9	11
IRF1	0.03	0.025	0.13	41	-10000	0	41
ESR1	0.021	0.005	-10000	0	-10000	0	0
KU/TER	0.03	0.006	-10000	0	-10000	0	0
ATM/TRF2	0.03	0.005	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.005	0.06	-10000	0	-0.25	14	14
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.005	0.061	-10000	0	-0.25	14	14
HDAC1	0.019	0.007	-10000	0	-10000	0	0
HDAC2	0.024	0.007	-10000	0	-10000	0	0
ATM	0.009	0.005	-10000	0	-10000	0	0
SMAD3	-0.013	0.006	0.047	1	-10000	0	1
ABL1	0.021	0.003	-10000	0	-10000	0	0
MXD1	0.023	0.002	-10000	0	-10000	0	0
MRE11A	0.021	0.003	-10000	0	-10000	0	0
HUS1	0.017	0.008	-10000	0	-10000	0	0
RPS6KB1	0.02	0.004	-10000	0	-10000	0	0
TERT/NF kappa B1/14-3-3	0.071	0.084	-10000	0	-10000	0	0
NR2F2	0.006	0.018	-10000	0	-0.017	251	251
MAPK3	-0.004	0.012	-10000	0	-10000	0	0
MAPK1	-0.004	0.012	-10000	0	-10000	0	0
TGFB1/TGF beta receptor Type II	0.018	0.008	0.12	1	-10000	0	1
NFKB1	0.021	0.002	-10000	0	-10000	0	0
HNRNPC	0.02	0.004	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.009	0.005	-10000	0	-10000	0	0
NBN	0.02	0.005	-10000	0	-10000	0	0
EGFR	0.053	0.054	0.12	235	-10000	0	235
mol:Oestrogen	0.001	0.001	-10000	0	-10000	0	0
EGF/EGFR	0.052	0.045	0.11	237	-10000	0	237
MYC	0.049	0.048	0.13	180	-10000	0	180
IL2	0.02	0.006	-10000	0	-10000	0	0
KU	0.03	0.006	-10000	0	-10000	0	0
RAD50	0.021	0.002	-10000	0	-10000	0	0
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
TGFB1	0.018	0.008	0.12	1	-10000	0	1
TRF2/BLM	0.035	0.021	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
KU/TERT	0.076	0.08	-10000	0	-10000	0	0
SP1/HDAC2	0.038	0.014	-10000	0	-10000	0	0
PINX1	0.021	0.003	-10000	0	-10000	0	0
Telomerase/EST1A	0.071	0.07	-10000	0	-0.37	1	1
Smad3/Myc	0.026	0.042	0.096	158	-10000	0	158
911 complex	0.035	0.017	-10000	0	-10000	0	0
IFNG	0.02	0.01	0.13	5	-10000	0	5
Telomerase/PinX1	0.068	0.07	-10000	0	-0.37	1	1
Telomerase/AKT1/mTOR/p70S6K	0.021	0.08	-10000	0	-0.38	12	12
SIN3B	0.021	0.004	-10000	0	-10000	0	0
YWHAE	0.021	0.002	-10000	0	-10000	0	0
Telomerase/EST1B	0.069	0.07	-10000	0	-0.38	1	1
response to DNA damage stimulus	0.004	0.006	-10000	0	-0.1	1	1
MRN complex/TRF2/Rap1	0.054	0.018	-10000	0	-10000	0	0
TRF2/WRN	0.028	0.006	-10000	0	-10000	0	0
Telomerase/hnRNP C1/C2	0.07	0.069	-10000	0	-0.38	1	1
E2F1	0.024	0.013	0.13	7	-10000	0	7
ZNFX1	0.021	0.004	-10000	0	-10000	0	0
PIF1	0.036	0.037	0.12	101	-10000	0	101
NCL	0.021	0.002	-10000	0	-10000	0	0
DKC1	0.021	0.002	-10000	0	-10000	0	0
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	0.024	0.021	0.12	27	-10000	0	27
GNB1/GNG2	0.029	0.053	-10000	0	-0.23	7	7
mol:DAG	0.008	0.048	0.18	9	-0.23	6	15
PLCG1	0.008	0.049	0.19	9	-0.24	6	15
YES1	-0.002	0.037	-10000	0	-0.18	14	14
FZD3	0.021	0.003	-10000	0	-10000	0	0
FZD6	0.021	0.012	0.12	7	-10000	0	7
G protein	0.03	0.058	0.18	28	-0.24	6	34
MAP3K7	-0.016	0.05	0.18	3	-0.17	51	54
mol:Ca2+	0.008	0.047	0.18	9	-0.22	6	15
mol:IP3	0.008	0.048	0.18	9	-0.23	6	15
NLK	0.001	0.046	-10000	0	-0.82	2	2
GNB1	0.019	0.007	-10000	0	-10000	0	0
CAMK2A	-0.009	0.043	0.19	3	-0.22	18	21
MAP3K7IP1	0	0	-10000	0	-10000	0	0
Noncanonical Wnts/FZD	0.013	0.035	-10000	0	-0.19	16	16
CSNK1A1	0.021	0.003	-10000	0	-10000	0	0
GNAS	-0.002	0.038	-10000	0	-0.18	14	14
GO:0007205	0.001	0.048	0.18	9	-0.22	7	16
WNT6	0.022	0.009	0.12	5	-10000	0	5
WNT4	0.019	0.009	0.12	2	-10000	0	2
NFAT1/CK1 alpha	0.026	0.056	0.21	9	-0.22	6	15
GNG2	0.02	0.004	-10000	0	-10000	0	0
WNT5A	0.028	0.026	0.12	45	-10000	0	45
WNT11	0.022	0.01	0.12	6	-10000	0	6
CDC42	-0.002	0.026	0.14	5	-0.16	9	14

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.032	0.054	0.26	16	-0.24	6	22
PDGFB-D/PDGFRB/SLAP	0.031	0.014	0.11	13	-10000	0	13
PDGFB-D/PDGFRB/APS/CBL	0.036	0.023	-10000	0	-10000	0	0
AKT1	-0.005	0.064	0.18	66	-10000	0	66
mol:PI-4-5-P2	0	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.037	0.062	0.24	26	-0.27	6	32
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
FGR	-0.019	0.11	0.21	1	-0.35	63	64
mol:Ca2+	0.027	0.062	0.23	24	-0.28	6	30
MYC	0.083	0.11	0.32	85	-0.32	1	86
SHC1	0.023	0.016	0.12	16	-10000	0	16
HRAS/GDP	0.017	0.012	-10000	0	-10000	0	0
LRP1/PDGFRB/PDGFB	0.041	0.013	-10000	0	-10000	0	0
GRB10	0.017	0.008	-10000	0	-10000	0	0
PTPN11	0.021	0.003	-10000	0	-10000	0	0
GO:0007205	0.027	0.062	0.23	24	-0.29	6	30
PTEN	0.018	0.007	-10000	0	-10000	0	0
GRB2	0.02	0.004	-10000	0	-10000	0	0
GRB7	0.02	0.009	0.12	4	-10000	0	4
PDGFB-D/PDGFRB/SHP2	0.032	0.008	0.11	3	-10000	0	3
PDGFB-D/PDGFRB/GRB10	0.027	0.013	0.11	1	-10000	0	1
cell cycle arrest	0.031	0.014	0.11	13	-10000	0	13
HRAS	0.02	0.005	-10000	0	-10000	0	0
HIF1A	-0.008	0.058	0.16	63	-10000	0	63
GAB1	0.033	0.07	0.25	21	-0.29	10	31
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	0.033	0.074	0.25	40	-0.25	7	47
PDGFB-D/PDGFRB	0.046	0.016	0.14	1	-10000	0	1
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.032	0.008	0.11	2	-10000	0	2
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.035	0.041	0.19	13	-0.21	4	17
positive regulation of MAPKKK cascade	0.032	0.008	0.11	3	-10000	0	3
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
mol:IP3	0.027	0.062	0.23	24	-0.29	6	30
E5	0	0.001	-10000	0	-10000	0	0
CSK	0.018	0.009	-10000	0	-0.02	30	30
PDGFB-D/PDGFRB/GRB7	0.032	0.01	0.11	7	-10000	0	7
SHB	0.02	0.004	-10000	0	-10000	0	0
BLK	0.019	0.039	0.25	1	-0.34	4	5
PTPN2	0.022	0.004	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.032	0.008	0.11	3	-10000	0	3
BCAR1	0.021	0.003	-10000	0	-10000	0	0
VAV2	0.041	0.074	0.25	29	-0.28	10	39
CBL	0.021	0.003	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.032	0.008	0.11	3	-10000	0	3
LCK	-0.009	0.12	0.24	6	-0.35	63	69
PDGFRB	0.023	0.009	0.13	4	-0.021	1	5
ACP1	0.021	0.003	-10000	0	-10000	0	0
HCK	0.014	0.02	-10000	0	-10000	0	0
ABL1	0.027	0.071	0.23	28	-0.3	9	37
PDGFB-D/PDGFRB/CBL	0.035	0.072	0.26	15	-0.32	12	27
PTPN1	0.021	0.005	-10000	0	-0.018	1	1
SNX15	0.021	0.003	-10000	0	-10000	0	0
STAT3	0.021	0.002	-10000	0	-10000	0	0
STAT1	0.022	0.011	0.12	7	-10000	0	7
cell proliferation	0.082	0.11	0.31	86	-0.3	1	87
SLA	0.021	0.015	0.12	11	-10000	0	11
actin cytoskeleton reorganization	-0.01	0.046	0.18	32	-10000	0	32
SRC	0.013	0.018	-10000	0	-10000	0	0
PI3K	-0.022	0.01	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	0.044	0.016	0.18	2	-10000	0	2
SH2B2	0.02	0.02	0.12	20	-10000	0	20
PLCgamma1/SPHK1	0.037	0.063	0.25	25	-0.27	6	31
LYN	0.014	0.027	-10000	0	-0.34	2	2
LRP1	0.02	0.004	-10000	0	-10000	0	0
SOS1	0.021	0.001	-10000	0	-10000	0	0
STAT5B	0.021	0.002	-10000	0	-10000	0	0
STAT5A	0.021	0.002	-10000	0	-10000	0	0
NCK1-2/p130 Cas	0.063	0.023	-10000	0	-10000	0	0
SPHK1	0.022	0.011	0.12	6	-10000	0	6
EDG1	0.001	0.003	-10000	0	-10000	0	0
mol:DAG	0.027	0.062	0.23	24	-0.29	6	30
PLCG1	0.027	0.063	0.24	24	-0.3	6	30
NHERF/PDGFRB	0.042	0.011	-10000	0	-10000	0	0
YES1	0.005	0.071	0.18	1	-0.49	12	13
cell migration	0.042	0.011	-10000	0	-10000	0	0
SHC/Grb2/SOS1	0.062	0.026	0.18	1	-10000	0	1
SLC9A3R2	0.021	0.002	-10000	0	-10000	0	0
SLC9A3R1	0.021	0.003	-10000	0	-10000	0	0
NHERF1-2/PDGFRB/PTEN	0.047	0.021	-10000	0	-10000	0	0
FYN	0.001	0.076	-10000	0	-0.37	24	24
DOK1	-0.012	0.013	0.1	4	-10000	0	4
HRAS/GTP	0.015	0.003	-10000	0	-10000	0	0
PDGFB	0.02	0.004	-10000	0	-10000	0	0
RAC1	0.07	0.1	0.28	81	-0.3	5	86
PRKCD	-0.008	0.015	0.2	1	-10000	0	1
FER	-0.009	0.015	0.2	1	-10000	0	1
MAPKKK cascade	-0.003	0.057	0.18	58	-10000	0	58
RASA1	-0.009	0.015	0.2	1	-10000	0	1
NCK1	0.021	0.005	0.12	1	-10000	0	1
NCK2	0.021	0.001	-10000	0	-10000	0	0
p62DOK/Csk	0.006	0.03	0.16	15	-10000	0	15
PDGFB-D/PDGFRB/SHB	0.031	0.009	0.11	3	-10000	0	3
chemotaxis	0.027	0.07	0.23	29	-0.29	9	38
STAT1-3-5/STAT1-3-5	0.051	0.018	-10000	0	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0.017	0.007	0.09	4	-10000	0	4
PTPRJ	0.021	0.003	-10000	0	-10000	0	0

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.036	0.034	-10000	0	-0.13	24	24
E-cadherin/beta catenin	0.025	0.037	0.11	9	-0.16	24	33
CTNNB1	0.021	0.002	-10000	0	-10000	0	0
JUP	0.021	0.006	0.12	2	-10000	0	2
CDH1	0.022	0.013	0.12	9	-10000	0	9

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.038	0.026	0.18	1	-10000	0	1
alphaV beta3 Integrin	0.054	0.028	-10000	0	-10000	0	0
PTK2	0.018	0.067	0.24	18	-0.38	2	20
IGF1R	0.021	0.003	-10000	0	-10000	0	0
PI4KB	0.021	0.002	-10000	0	-10000	0	0
MFGE8	0.021	0.006	0.12	2	-10000	0	2
SRC	0.02	0.004	-10000	0	-10000	0	0
CDKN1B	0.017	0.014	-10000	0	-0.31	1	1
VEGFA	0.033	0.034	0.12	79	-10000	0	79
ILK	0.016	0.019	-10000	0	-0.31	2	2
ROCK1	0.021	0.005	0.12	1	-10000	0	1
AKT1	0.007	0.017	-10000	0	-0.29	2	2
PTK2B	-0.001	0.045	0.18	31	-10000	0	31
alphaV/beta3 Integrin/JAM-A	0.056	0.03	0.17	4	-0.11	2	6
CBL	0.021	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.048	0.031	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.05	0.021	-10000	0	-0.12	7	7
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.018	0.03	0.13	9	-0.2	1	10
alphaV/beta3 Integrin/Syndecan-1	0.058	0.037	0.18	32	-0.13	1	33
PI4KA	0.02	0.004	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.056	0.033	-10000	0	-0.11	7	7
PI4 Kinase	0.029	0.017	-10000	0	-0.16	5	5
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	0.064	0.045	0.18	58	-0.13	3	61
RPS6KB1	-0.019	0.031	0.18	10	-10000	0	10
TLN1	0.02	0.005	-10000	0	-10000	0	0
MAPK3	0.011	0.042	-10000	0	-0.27	10	10
GPR124	0.021	0.003	-10000	0	-10000	0	0
MAPK1	0.012	0.038	-10000	0	-0.27	8	8
PXN	0.021	0.002	-10000	0	-10000	0	0
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	0.057	0.036	0.18	5	-0.12	7	12
cell adhesion	0.039	0.036	-10000	0	-10000	0	0
ANGPTL3	0.016	0.007	0.12	1	-10000	0	1
VEGFR2 homodimer/VEGFA homodimer/Src	0.045	0.025	0.18	1	-10000	0	1
IGF-1R heterotetramer	0.021	0.003	-10000	0	-10000	0	0
Rac1/GDP	0.013	0.006	-10000	0	-10000	0	0
TGFBR2	0.021	0.007	0.12	3	-10000	0	3
ITGB3	0.04	0.04	0.12	124	-10000	0	124
IGF1	0.021	0.005	0.12	1	-10000	0	1
RAC1	0.018	0.008	-10000	0	-10000	0	0
regulation of cell-matrix adhesion	0.053	0.027	-10000	0	-10000	0	0
apoptosis	0.021	0.001	-10000	0	-10000	0	0
CD47	0.021	0.003	-10000	0	-10000	0	0
alphaV/beta3 Integrin/CD47	0.054	0.027	-10000	0	-10000	0	0
VCL	0.02	0.01	0.12	4	-10000	0	4
alphaV/beta3 Integrin/Del1	0.03	0.068	-10000	0	-0.13	89	89
CSF1	0.02	0.015	0.12	10	-10000	0	10
PIK3C2A	0.017	0.019	-10000	0	-0.31	2	2
PI4 Kinase/Pyk2	0.032	0.024	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.069	0.043	0.18	56	-10000	0	56
FAK1/Vinculin	0.022	0.053	0.22	13	-0.3	2	15
alphaV beta3/Integrin/ppsTEM5	0.054	0.028	-10000	0	-10000	0	0
RHOA	0.021	0.003	-10000	0	-10000	0	0
VTN	0.021	0.006	0.12	2	-10000	0	2
BCAR1	0.021	0.003	-10000	0	-10000	0	0
FGF2	0.021	0.005	0.12	1	-10000	0	1
F11R	-0.012	0.006	0.051	5	-10000	0	5
alphaV/beta3 Integrin/Lactadherin	0.054	0.028	0.18	1	-10000	0	1
alphaV/beta3 Integrin/TGFBR2	0.055	0.028	0.18	2	-10000	0	2
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.047	0.022	-10000	0	-10000	0	0
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	0.049	0.027	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.036	0.036	0.12	94	-10000	0	94
alphaV/beta3 Integrin/Pyk2	0.048	0.04	0.14	62	-0.12	1	63
SDC1	0.027	0.024	0.12	38	-10000	0	38
VAV3	-0.01	0.03	0.17	14	-10000	0	14
PTPN11	0.021	0.003	-10000	0	-10000	0	0
IRS1	0.021	0.001	-10000	0	-10000	0	0
FAK1/Paxillin	0.026	0.061	0.23	19	-0.31	2	21
cell migration	0.014	0.05	0.19	17	-0.28	2	19
ITGAV	0.021	0.001	-10000	0	-10000	0	0
PI3K	0.06	0.028	0.18	2	-0.1	2	4
SPP1	0.036	0.037	0.12	96	-10000	0	96
KDR	0.021	0.012	0.12	8	-10000	0	8
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.021	0.001	-10000	0	-10000	0	0
COL4A3	0.027	0.025	0.12	41	-10000	0	41
angiogenesis	0.014	0.044	0.22	3	-0.28	8	11
Rac1/GTP	-0.016	0.038	0.16	14	-10000	0	14
EDIL3	0.018	0.008	-10000	0	-10000	0	0
cell proliferation	0.054	0.028	0.18	2	-10000	0	2

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	0.045	0.029	-10000	0	-10000	0	0
AKT1	0.019	0.057	0.29	5	-0.3	1	6
PTK2B	-0.001	0.047	0.19	31	-10000	0	31
VEGFR2 homodimer/Frs2	0.022	0.009	-10000	0	-10000	0	0
CAV1	0.028	0.035	0.12	73	-10000	0	73
CALM1	0.02	0.005	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.043	0.029	0.21	7	-10000	0	7
endothelial cell proliferation	0.005	0.069	0.26	12	-0.31	4	16
mol:Ca2+	0.001	0.039	0.18	22	-10000	0	22
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.044	0.03	0.21	3	-10000	0	3
RP11-342D11.1	-0.002	0.025	0.19	8	-10000	0	8
CDH5	0.022	0.01	0.12	6	-10000	0	6
VEGFA homodimer	0.057	0.025	0.18	1	-10000	0	1
SHC1	0.023	0.016	0.12	16	-10000	0	16
SHC2	0.02	0.004	-10000	0	-10000	0	0
HRAS/GDP	0.038	0.022	-10000	0	-10000	0	0
SH2D2A	0.021	0.01	0.12	5	-10000	0	5
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.05	0.053	0.25	9	-0.37	1	10
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.041	0.039	0.21	8	-10000	0	8
VEGFR1 homodimer	0.02	0.005	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.066	0.036	0.22	2	-10000	0	2
GRB10	-0.001	0.032	0.18	14	-10000	0	14
PTPN11	0.021	0.003	-10000	0	-10000	0	0
GRB2	0.02	0.004	-10000	0	-10000	0	0
PAK1	0.015	0.009	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.061	0.033	0.22	9	-10000	0	9
HRAS	0.02	0.005	-10000	0	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	0.019	0.035	0.17	6	-0.33	1	7
HIF1A	0.021	0.008	0.12	3	-10000	0	3
FRS2	0.02	0.004	-10000	0	-10000	0	0
oxygen and reactive oxygen species metabolic process	0.043	0.029	0.21	3	-10000	0	3
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.025	0.021	0.12	29	-10000	0	29
Nck/Pak	-0.018	0.082	-10000	0	-0.16	170	170
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.042	0.03	0.21	8	-10000	0	8
mol:GDP	0.051	0.028	0.18	2	-10000	0	2
mol:NADP	0.026	0.052	0.25	10	-0.37	1	11
eNOS/Hsp90	0.036	0.047	0.27	6	-0.35	1	7
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
mol:IP3	0.001	0.039	0.18	22	-10000	0	22
HIF1A/ARNT	0.03	0.009	-10000	0	-10000	0	0
SHB	0.02	0.004	-10000	0	-10000	0	0
VEGFA	0.034	0.034	0.12	79	-10000	0	79
VEGFC	0.022	0.012	0.12	8	-10000	0	8
FAK1/Vinculin	0.027	0.047	0.23	6	-0.49	1	7
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.021	0.003	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.067	0.048	0.26	9	-10000	0	9
PTPN6	0.021	0.009	0.12	4	-10000	0	4
EPAS1	0.025	0.005	-10000	0	-10000	0	0
mol:L-citrulline	0.026	0.052	0.25	10	-0.37	1	11
ITGAV	0.021	0.001	-10000	0	-10000	0	0
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.051	0.031	0.21	7	-10000	0	7
VEGFR2 homodimer/VEGFA homodimer	0.054	0.037	0.21	8	-10000	0	8
VEGFR2/3 heterodimer	0.026	0.021	0.18	5	-10000	0	5
VEGFB	0.021	0.003	-10000	0	-10000	0	0
MAPK11	0	0.046	0.2	23	-10000	0	23
VEGFR2 homodimer	0.01	0.01	-10000	0	-10000	0	0
FLT1	0.02	0.005	-10000	0	-10000	0	0
NEDD4	0.034	0.034	0.12	81	-10000	0	81
MAPK3	-0.018	0.045	0.19	14	-10000	0	14
MAPK1	-0.018	0.045	0.19	12	-10000	0	12
VEGFA145/NRP2	0.041	0.026	0.18	2	-10000	0	2
VEGFR1/2 heterodimer	0.022	0.01	-10000	0	-10000	0	0
KDR	0.01	0.01	-10000	0	-10000	0	0
VEGFA165/NRP1/VEGFR2 homodimer	0.049	0.032	0.2	10	-10000	0	10
SRC	0.02	0.004	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	-0.013	0.053	0.21	14	-10000	0	14
PI3K	0.028	0.037	0.19	5	-10000	0	5
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.044	0.029	0.21	7	-10000	0	7
FES	0.001	0.039	0.18	22	-10000	0	22
GAB1	0.019	0.042	0.19	6	-10000	0	6
VEGFR2 homodimer/VEGFA homodimer/Src	0.042	0.03	0.21	8	-10000	0	8
CTNNB1	0.021	0.002	-10000	0	-10000	0	0
SOS1	0.021	0.001	-10000	0	-10000	0	0
ARNT	0.021	0.002	-10000	0	-10000	0	0
eNOS/Caveolin-1	0.029	0.046	0.25	7	-0.35	1	8
VEGFR2 homodimer/VEGFA homodimer/Yes	0.043	0.031	0.21	8	-10000	0	8
PI3K/GAB1	0.03	0.05	0.25	3	-10000	0	3
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.017	0.079	0.21	5	-10000	0	5
PRKACA	0.02	0.004	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.037	0.023	0.21	2	-10000	0	2
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
CDC42	0.002	0.039	0.19	22	-10000	0	22
actin cytoskeleton reorganization	0.04	0.039	0.21	8	-10000	0	8
PTK2	0.018	0.043	0.22	9	-10000	0	9
EDG1	-0.002	0.025	0.19	8	-10000	0	8
mol:DAG	0.001	0.039	0.18	22	-10000	0	22
CaM/Ca2+	0	0.039	0.17	21	-10000	0	21
MAP2K3	-0.007	0.04	0.18	27	-10000	0	27
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.073	0.072	0.23	96	-10000	0	96
PLCG1	0.001	0.039	0.18	22	-10000	0	22
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.051	0.031	0.21	8	-10000	0	8
IQGAP1	0.022	0.01	0.12	6	-10000	0	6
YES1	0.02	0.004	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.044	0.03	0.21	8	-10000	0	8
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.043	0.031	0.21	7	-10000	0	7
cell migration	0.031	0.056	0.24	12	-0.48	1	13
mol:PI-3-4-5-P3	0.027	0.036	0.19	5	-10000	0	5
FYN	0.02	0.004	-10000	0	-10000	0	0
VEGFB/NRP1	0.002	0.038	0.17	23	-10000	0	23
mol:NO	0.026	0.052	0.25	10	-0.37	1	11
PXN	0.021	0.002	-10000	0	-10000	0	0
HRAS/GTP	-0.008	0.026	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.038	0.042	0.2	28	-10000	0	28
VHL	0.021	0.003	-10000	0	-10000	0	0
ITGB3	0.04	0.04	0.12	124	-10000	0	124
NOS3	0.026	0.054	0.28	7	-0.41	1	8
VEGFR2 homodimer/VEGFA homodimer/Sck	0.042	0.029	0.21	7	-10000	0	7
RAC1	0.018	0.008	-10000	0	-10000	0	0
PRKCA	-0.007	0.041	0.18	27	-10000	0	27
PRKCB	-0.007	0.029	0.18	13	-10000	0	13
VCL	0.02	0.01	0.12	4	-10000	0	4
VEGFA165/NRP1	0.032	0.039	0.2	23	-10000	0	23
VEGFR1/2 heterodimer/VEGFA homodimer	0.041	0.029	0.21	6	-10000	0	6
VEGFA165/NRP2	0.041	0.026	0.18	2	-10000	0	2
MAPKKK cascade	0.008	0.061	0.18	52	-10000	0	52
NRP2	0.022	0.01	0.12	6	-10000	0	6
VEGFC homodimer	0.022	0.012	0.12	8	-10000	0	8
NCK1	0.021	0.005	0.12	1	-10000	0	1
ROCK1	0.021	0.005	0.12	1	-10000	0	1
FAK1/Paxillin	0.034	0.054	0.23	13	-0.5	1	14
MAP3K13	0	0.038	0.18	21	-10000	0	21
PDPK1	0.003	0.039	0.18	6	-10000	0	6

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
GNAO1	0.021	0.003	-10000	0	-10000	0	0
CDC42/GTP	0.019	0.047	-10000	0	-0.23	5	5
PLCG1	0.004	0.043	-10000	0	-0.18	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.021	0.003	-10000	0	-10000	0	0
GNAI3	0.019	0.008	0.12	1	-10000	0	1
G12/G13	0.026	0.012	-10000	0	-10000	0	0
cell migration	0.018	0.046	-10000	0	-0.23	5	5
S1PR5	0.017	0.008	-10000	0	-10000	0	0
S1PR4	0.021	0.011	0.12	6	-10000	0	6
MAPK3	0.005	0.044	-10000	0	-0.18	9	9
MAPK1	0.006	0.043	-10000	0	-0.18	9	9
S1P/S1P5/Gi	-0.016	0.064	-10000	0	-0.18	72	72
GNAI1	0.017	0.008	-10000	0	-10000	0	0
CDC42/GDP	0.014	0.005	-10000	0	-10000	0	0
S1P/S1P5/G12	0.006	0.048	-10000	0	-0.13	73	73
RHOA	0.023	0.084	0.19	123	-0.11	1	124
S1P/S1P4/Gi	0	0.037	-10000	0	-0.18	9	9
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	0.02	0.004	-10000	0	-10000	0	0
S1P/S1P4/G12/G13	0.033	0.018	-10000	0	-0.12	1	1
GNA12	0.018	0.008	-10000	0	-10000	0	0
GNA13	0.02	0.004	-10000	0	-10000	0	0
CDC42	0.019	0.006	-10000	0	-10000	0	0

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.008	0.14	-10000	0	-0.57	12	12
PCK1	0.006	0.13	-10000	0	-0.84	8	8
HNF4A	-0.025	0.19	-10000	0	-0.68	33	33
KCNJ11	-0.006	0.18	-10000	0	-0.68	21	21
AKT1	0.011	0.11	-10000	0	-0.35	14	14
response to starvation	0.001	0.002	-10000	0	-10000	0	0
DLK1	0.002	0.16	-10000	0	-0.64	9	9
NKX2-1	-0.005	0.095	0.27	2	-0.31	20	22
ACADM	-0.006	0.14	-10000	0	-0.57	11	11
TAT	0.022	0.1	-10000	0	-0.5	1	1
CEBPB	0.022	0.008	0.12	2	-10000	0	2
CEBPA	0.021	0.012	0.13	4	-10000	0	4
TTR	0.001	0.17	0.44	13	-0.7	12	25
PKLR	-0.009	0.15	-10000	0	-0.7	10	10
APOA1	-0.015	0.19	-10000	0	-0.8	11	11
CPT1C	-0.006	0.14	-10000	0	-0.58	12	12
ALAS1	0.017	0.097	-10000	0	-0.52	1	1
TFRC	0.012	0.14	-10000	0	-0.68	8	8
FOXF1	0.022	0.009	0.12	5	-10000	0	5
NF1	0.023	0.003	-10000	0	-10000	0	0
HNF1A (dimer)	0.024	0.008	-10000	0	-10000	0	0
CPT1A	-0.006	0.14	-10000	0	-0.57	12	12
HMGCS1	-0.008	0.14	-10000	0	-0.6	9	9
NR3C1	0.04	0.019	-10000	0	-10000	0	0
CPT1B	-0.008	0.14	-10000	0	-0.58	13	13
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.023	0.008	-10000	0	-10000	0	0
GCK	-0.006	0.19	0.34	9	-0.69	31	40
CREB1	0.023	0.019	-10000	0	-0.19	5	5
IGFBP1	0.037	0.086	-10000	0	-10000	0	0
PDX1	0.013	0.096	-10000	0	-10000	0	0
UCP2	-0.004	0.14	-10000	0	-0.57	12	12
ALDOB	-0.004	0.16	-10000	0	-0.65	15	15
AFP	0.021	0.039	-10000	0	-0.26	3	3
BDH1	-0.022	0.19	-10000	0	-0.7	31	31
HADH	-0.002	0.16	-10000	0	-0.6	13	13
F2	-0.018	0.2	-10000	0	-0.82	10	10
HNF1A	0.024	0.008	-10000	0	-10000	0	0
G6PC	0.021	0.031	-10000	0	-10000	0	0
SLC2A2	0.011	0.11	-10000	0	-0.57	2	2
INS	-0.027	0.017	0.12	1	-10000	0	1
FOXA1	0.032	0.04	0.17	14	-0.24	5	19
FOXA3	0.047	0.055	0.18	21	-0.2	10	31
FOXA2	0.009	0.19	-10000	0	-0.63	24	24
ABCC8	-0.032	0.23	-10000	0	-0.72	55	55
ALB	0.015	0.074	-10000	0	-0.72	6	6

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	-0.012	0.003	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.029	0.011	-10000	0	-10000	0	0
CDKN1B	0.002	0.065	0.19	12	-0.29	25	37
CDKN1A	0.002	0.058	0.19	1	-0.29	22	23
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.021	0.003	-10000	0	-10000	0	0
FOXO3	0.003	0.048	0.19	1	-0.29	15	16
AKT1	-0.003	0.062	-10000	0	-0.3	27	27
BAD	0.021	0.003	-10000	0	-10000	0	0
AKT3	0.009	0.002	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	-0.001	0.063	0.19	3	-0.3	26	29
AKT1/ASK1	0.014	0.063	-10000	0	-0.28	26	26
BAD/YWHAZ	0.038	0.013	-10000	0	-10000	0	0
RICTOR	0.021	0.002	-10000	0	-10000	0	0
RAF1	0.021	0.003	-10000	0	-10000	0	0
JNK cascade	-0.014	0.061	0.27	26	-10000	0	26
TSC1	-0.001	0.061	0.19	2	-0.29	25	27
YWHAZ	0.02	0.005	-10000	0	-10000	0	0
AKT1/RAF1	0.016	0.066	0.22	1	-0.29	27	28
EP300	0.02	0.004	-10000	0	-10000	0	0
mol:GDP	-0.003	0.062	-10000	0	-0.3	27	27
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	-0.003	0.062	0.19	1	-0.29	27	28
YWHAQ	0.021	0.002	-10000	0	-10000	0	0
TBC1D4	-0.003	0.001	-10000	0	-10000	0	0
MAP3K5	0.02	0.005	-10000	0	-10000	0	0
MAPKAP1	0.021	0.003	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.017	0.057	0.38	3	-0.15	3	6
YWHAH	0.02	0.005	-10000	0	-10000	0	0
AKT1S1	0.003	0.048	0.19	5	-0.29	14	19
CASP9	0	0.058	0.19	2	-0.29	22	24
YWHAB	0.02	0.004	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.016	0.07	0.24	4	-0.28	27	31
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.039	0.013	-10000	0	-10000	0	0
YWHAE	0.021	0.002	-10000	0	-10000	0	0
SRC	0.02	0.004	-10000	0	-10000	0	0
AKT2/p21CIP1	-0.001	0.053	0.21	2	-0.26	25	27
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.005	0.02	-10000	0	-10000	0	0
CHUK	-0.001	0.053	-10000	0	-0.29	20	20
BAD/BCL-XL	0.015	0.063	-10000	0	-0.28	27	27
mTORC2	0.026	0.005	-10000	0	-10000	0	0
AKT2	0.008	0.003	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.01	0.072	0.21	1	-0.32	12	13
PDPK1	0.021	0.002	-10000	0	-10000	0	0
MDM2	0.003	0.065	0.19	15	-0.29	24	39
MAPKKK cascade	-0.016	0.065	0.28	27	-0.21	1	28
MDM2/Cbp/p300	0.026	0.068	0.24	3	-0.28	25	28
TSC1/TSC2	-0.003	0.066	0.22	11	-0.29	27	38
proteasomal ubiquitin-dependent protein catabolic process	0.024	0.066	0.23	3	-0.27	25	28
glucose import	-0.008	0.016	-10000	0	-0.11	15	15
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.008	0.044	0.18	11	-0.17	17	28
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.006	0.003	-10000	0	-10000	0	0
GSK3A	0.003	0.05	0.19	6	-0.29	15	21
FOXO1	-0.002	0.06	0.19	1	-0.29	25	26
GSK3B	-0.001	0.061	0.19	1	-0.29	25	26
SFN	0.022	0.02	0.12	23	-10000	0	23
G1/S transition of mitotic cell cycle	-0.001	0.068	0.22	16	-0.28	26	42
p27Kip1/14-3-3 family	0.024	0.053	-10000	0	-0.6	2	2
PRKACA	0.02	0.004	-10000	0	-10000	0	0
KPNA1	0.021	0.003	-10000	0	-10000	0	0
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
YWHAG	0.017	0.008	-10000	0	-10000	0	0
RHEB	0.017	0.009	-10000	0	-10000	0	0
CREBBP	0.021	0.002	-10000	0	-10000	0	0

×

Nectin adhesion 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.021	0.008	0.12	4	-10000	0	4
alphaV beta3 Integrin	0.045	0.029	-10000	0	-10000	0	0
PTK2	0.013	0.063	-10000	0	-0.26	9	9
positive regulation of JNK cascade	-0.004	0.081	-10000	0	-0.28	19	19
CDC42/GDP	0.006	0.11	-10000	0	-0.34	30	30
Rac1/GDP	0.005	0.096	-10000	0	-0.34	21	21
RAP1B	0.021	0.009	0.12	4	-10000	0	4
RAP1A	0.019	0.007	-10000	0	-10000	0	0
CTNNB1	0.021	0.002	-10000	0	-10000	0	0
CDC42/GTP	0	0.1	-10000	0	-0.34	19	19
nectin-3/I-afadin	0.028	0.018	-10000	0	-0.15	5	5
RAPGEF1	-0.007	0.098	0.24	1	-0.33	35	36
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.011	0.1	-10000	0	-0.36	34	34
PDGFB-D/PDGFRB	0.021	0.008	0.12	4	-10000	0	4
TLN1	-0.007	0.007	-10000	0	-0.1	3	3
Rap1/GTP	-0.004	0.073	-10000	0	-0.25	35	35
IQGAP1	0.022	0.01	0.12	6	-10000	0	6
Rap1/GTP/I-afadin	0.033	0.017	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.028	0.018	-10000	0	-0.15	5	5
PVR	0.019	0.007	-10000	0	-10000	0	0
Necl-5(dimer)	0.019	0.007	-10000	0	-10000	0	0
mol:GDP	-0.005	0.12	-10000	0	-0.41	30	30
MLLT4	0.02	0.005	-10000	0	-10000	0	0
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
PI3K	0.055	0.025	-10000	0	-0.12	5	5
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.027	0.02	-10000	0	-0.16	6	6
positive regulation of lamellipodium assembly	0	0.075	-10000	0	-0.28	16	16
PVRL1	0.02	0.004	-10000	0	-10000	0	0
PVRL3	0.021	0.003	-10000	0	-10000	0	0
PVRL2	0.019	0.007	-10000	0	-10000	0	0
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
CDH1	0.022	0.013	0.12	9	-10000	0	9
CLDN1	0.02	0.004	-10000	0	-10000	0	0
JAM-A/CLDN1	0.046	0.03	-10000	0	-0.12	14	14
SRC	-0.011	0.11	-10000	0	-0.39	36	36
ITGB3	0.04	0.04	0.12	124	-10000	0	124
nectin-1(dimer)/I-afadin/I-afadin	0.027	0.02	-10000	0	-0.16	6	6
FARP2	-0.006	0.13	-10000	0	-0.45	25	25
RAC1	0.018	0.008	-10000	0	-10000	0	0
CTNNA1	0.021	0.003	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.034	0.022	-10000	0	-0.13	5	5
nectin-1/I-afadin	0.027	0.02	-10000	0	-0.16	6	6
nectin-2/I-afadin	0.026	0.011	-10000	0	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0.024	0.012	0.096	5	-10000	0	5
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.036	0.025	-10000	0	-0.13	11	11
CDC42/GTP/IQGAP1/filamentous actin	0.026	0.011	-10000	0	-10000	0	0
F11R	0.022	0.008	0.12	4	-10000	0	4
positive regulation of filopodium formation	-0.004	0.081	-10000	0	-0.28	19	19
alphaV/beta3 Integrin/Talin	0.036	0.051	0.2	28	-0.13	7	35
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.026	0.011	-10000	0	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.026	0.011	-10000	0	-10000	0	0
PIP5K1C	-0.004	0.008	-10000	0	-0.1	4	4
VAV2	-0.003	0.13	-10000	0	-0.5	17	17
RAP1/GDP	0.008	0.099	-10000	0	-0.31	34	34
ITGAV	0.021	0.001	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.034	0.022	-10000	0	-0.13	5	5
nectin-3(dimer)/I-afadin/I-afadin	0.028	0.018	-10000	0	-0.15	5	5
Rac1/GTP	0.002	0.09	-10000	0	-0.34	16	16
PTPRM	0.007	0.011	-10000	0	-0.11	5	5
E-cadherin/beta catenin/alpha catenin	0.043	0.043	-10000	0	-0.12	27	27
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.019	0.006	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.02	0.004	-10000	0	-10000	0	0
HDAC4	0.021	0.003	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.013	0.01	-10000	0	-0.05	3	3
CDKN1A	0	0.026	-10000	0	-10000	0	0
KAT2B	0.021	0.005	0.12	1	-10000	0	1
BAX	0.019	0.007	-10000	0	-10000	0	0
FOXO3	-0.001	0.005	-10000	0	-10000	0	0
FOXO1	0.02	0.004	-10000	0	-10000	0	0
FOXO4	0.008	0.008	-10000	0	-0.19	1	1
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.02	0.004	-10000	0	-10000	0	0
TAT	0.034	0.035	0.12	85	-10000	0	85
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.01	0.031	0.051	240	-10000	0	240
PPARGC1A	0.021	0.003	-10000	0	-10000	0	0
FHL2	0.02	0.005	-10000	0	-10000	0	0
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.019	0.021	-10000	0	-10000	0	0
HIST2H4A	-0.013	0.01	0.05	3	-10000	0	3
SIRT1/FOXO3a	0.007	0.022	-10000	0	-0.18	3	3
SIRT1	0.01	0.021	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.027	0.027	-10000	0	-0.15	1	1
SIRT1/Histone H1b	0.013	0.025	-10000	0	-0.21	2	2
apoptosis	-0.025	0.026	-10000	0	-10000	0	0
SIRT1/PGC1A	0.017	0.021	-10000	0	-0.13	3	3
p53/SIRT1	0.019	0.034	-10000	0	-10000	0	0
SIRT1/FOXO4	0.014	0.021	-10000	0	-0.18	1	1
FOXO1/FHL2/SIRT1	0.022	0.041	-10000	0	-0.12	45	45
HIST1H1E	0.008	0.004	-10000	0	-10000	0	0
SIRT1/p300	0.019	0.021	-10000	0	-10000	0	0
muscle cell differentiation	-0.022	0.024	-10000	0	-0.23	3	3
TP53	0.022	0.039	0.12	67	-10000	0	67
KU70/SIRT1/BAX	0.025	0.026	-10000	0	-10000	0	0
CREBBP	0.021	0.002	-10000	0	-10000	0	0
MEF2D	0.021	0.003	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.028	0.032	-10000	0	-10000	0	0
ACSS2	-0.014	0.008	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	0.022	0.025	0.24	3	-10000	0	3

×

TRAIL signaling 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.021	0.007	0.12	3	-10000	0	3
positive regulation of NF-kappaB transcription factor activity	0.031	0.011	0.1	10	-10000	0	10
MAP2K4	0.012	0.02	-10000	0	-0.2	1	1
IKBKB	0.021	0.003	-10000	0	-10000	0	0
TNFRSF10B	0.025	0.021	0.12	28	-10000	0	28
TNFRSF10A	0.021	0.005	0.12	1	-10000	0	1
SMPD1	0.009	0.005	-10000	0	-10000	0	0
IKBKG	0.021	0.002	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.022	0.011	0.12	7	-10000	0	7
TRAIL/TRAILR2	0.034	0.018	0.11	28	-10000	0	28
TRAIL/TRAILR3	0.044	0.03	0.11	118	-10000	0	118
TRAIL/TRAILR1	0.03	0.013	-10000	0	-0.16	2	2
TRAIL/TRAILR4	0.031	0.011	0.11	10	-10000	0	10
TRAIL/TRAILR1/DAP3/GTP	0.039	0.013	-10000	0	-0.12	2	2
IKK complex	-0.002	0.062	-10000	0	-0.2	56	56
RIPK1	0.021	0.003	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.015	0.002	-10000	0	-10000	0	0
MAPK3	-0.012	0.005	0.051	3	-10000	0	3
MAP3K1	0.019	0.016	-10000	0	-0.21	1	1
TRAILR4 (trimer)	0.022	0.011	0.12	7	-10000	0	7
TRADD	0.021	0.002	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.021	0.005	0.12	1	-10000	0	1
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.017	0.012	-10000	0	-0.16	2	2
CFLAR	0.021	0.001	-10000	0	-10000	0	0
MAPK1	-0.012	0.005	0.051	3	-10000	0	3
TRAIL/TRAILR1/FADD/TRADD/RIP	0.059	0.018	-10000	0	-0.12	1	1
mol:ceramide	0.009	0.005	-10000	0	-10000	0	0
FADD	0.021	0.003	-10000	0	-10000	0	0
MAPK8	0.007	0.023	0.19	1	-10000	0	1
TRAF2	0.021	0.003	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.039	0.04	0.12	118	-10000	0	118
CHUK	0.019	0.006	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	0.041	0.013	-10000	0	-0.13	1	1
DAP3	0.021	0.003	-10000	0	-10000	0	0
CASP10	-0.008	0.007	-10000	0	-10000	0	0
JNK cascade	0.031	0.011	0.1	10	-10000	0	10
TRAIL (trimer)	0.021	0.007	0.12	3	-10000	0	3
TNFRSF10C	0.039	0.04	0.12	118	-10000	0	118
TRAIL/TRAILR1/DAP3/GTP/FADD	0.047	0.015	-10000	0	-0.11	1	1
TRAIL/TRAILR2/FADD	0.044	0.018	0.18	2	-10000	0	2
cell death	0.009	0.005	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.019	0.011	-10000	0	-0.17	1	1
TRAILR2 (trimer)	0.025	0.021	0.12	28	-10000	0	28
CASP8	0.012	0.021	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.061	0.022	0.18	2	-10000	0	2

×

ceramide 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
MAP4K4	0.001	0.068	-10000	0	-0.37	10	10
BAG4	0.02	0.004	-10000	0	-10000	0	0
BAD	-0.001	0.035	0.18	9	-0.14	6	15
NFKBIA	0.021	0.008	0.12	3	-10000	0	3
BIRC3	0.023	0.017	0.12	16	-10000	0	16
BAX	0.002	0.036	0.18	15	-0.14	6	21
EnzymeConsortium:3.1.4.12	0.001	0.019	0.068	2	-0.084	11	13
IKBKB	0.001	0.072	0.2	13	-0.36	10	23
MAP2K2	-0.004	0.042	0.16	23	-0.13	3	26
MAP2K1	-0.007	0.036	0.17	10	-0.15	4	14
SMPD1	0	0.025	0.092	5	-0.1	15	20
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.005	0.074	0.25	6	-0.38	10	16
MAP2K4	-0.005	0.031	0.22	3	-0.15	3	6
protein ubiquitination	-0.001	0.069	0.2	1	-0.38	9	10
EnzymeConsortium:2.7.1.37	-0.008	0.041	0.17	10	-0.16	4	14
response to UV	0	0	0.002	11	-0.002	3	14
RAF1	-0.005	0.035	0.16	9	-0.14	7	16
CRADD	0.021	0.002	-10000	0	-10000	0	0
mol:ceramide	0.001	0.029	0.09	5	-0.12	12	17
I-kappa-B-alpha/RELA/p50/ubiquitin	0.027	0.008	0.096	3	-10000	0	3
MADD	0.02	0.004	-10000	0	-10000	0	0
MAP3K1	-0.002	0.03	0.16	4	-0.13	7	11
TRADD	0.021	0.002	-10000	0	-10000	0	0
RELA/p50	0.021	0.003	-10000	0	-10000	0	0
MAPK3	-0.003	0.04	0.14	24	-0.18	3	27
MAPK1	-0.005	0.042	0.14	24	-0.2	4	28
p50/RELA/I-kappa-B-alpha	0.03	0.009	-10000	0	-10000	0	0
FADD	0.003	0.069	0.24	4	-0.38	9	13
KSR1	-0.002	0.031	0.13	6	-0.13	9	15
MAPK8	-0.008	0.03	0.19	5	-0.19	1	6
TRAF2	0.021	0.003	-10000	0	-10000	0	0
response to radiation	0	0	0.002	2	-10000	0	2
CHUK	-0.002	0.062	-10000	0	-0.37	8	8
TNF R/SODD	0.027	0.022	-10000	0	-0.16	7	7
TNF	0.021	0.015	0.12	11	-10000	0	11
CYCS	0.01	0.045	0.15	27	-0.16	3	30
IKBKG	-0.001	0.067	0.19	5	-0.37	9	14
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.006	0.071	-10000	0	-0.4	9	9
RELA	0.021	0.003	-10000	0	-10000	0	0
RIPK1	0.021	0.003	-10000	0	-10000	0	0
AIFM1	0	0.035	0.14	18	-0.15	3	21
TNF/TNF R/SODD	0.028	0.049	-10000	0	-0.14	49	49
TNFRSF1A	0.021	0.01	0.12	5	-10000	0	5
response to heat	0	0	0.002	2	-10000	0	2
CASP8	0.023	0.069	-10000	0	-0.88	3	3
NSMAF	0.002	0.069	0.23	5	-0.37	10	15
response to hydrogen peroxide	0	0	0.002	11	-0.002	3	14
BCL2	0.021	0.003	-10000	0	-10000	0	0

×

FoxO family signaling

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
G6PC	0.011	0.04	-10000	0	-10000	0	0
PLK1	0.047	0.068	0.38	1	-10000	0	1
CDKN1B	0.026	0.12	0.33	5	-0.32	24	29
FOXO3	0.049	0.044	-10000	0	-10000	0	0
KAT2B	0.028	0.008	0.13	1	-10000	0	1
FOXO1/SIRT1	0.02	0.031	-10000	0	-10000	0	0
CAT	0.04	0.061	-10000	0	-10000	0	0
CTNNB1	0.021	0.002	-10000	0	-10000	0	0
AKT1	0.028	0.009	-10000	0	-10000	0	0
FOXO1	0.014	0.038	-10000	0	-10000	0	0
MAPK10	0.04	0.063	0.19	104	-10000	0	104
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
FOXO4	0.036	0.06	0.23	17	-10000	0	17
response to oxidative stress	0.009	0.007	0.035	3	-10000	0	3
FOXO3A/SIRT1	0.047	0.059	-10000	0	-0.42	1	1
XPO1	0.021	0.001	-10000	0	-10000	0	0
EP300	0.021	0.005	-10000	0	-10000	0	0
BCL2L11	0.027	0.041	-10000	0	-0.93	1	1
FOXO1/SKP2	0.024	0.036	-10000	0	-10000	0	0
mol:GDP	0.009	0.007	0.035	3	-10000	0	3
RAN	0.021	0.002	-10000	0	-10000	0	0
GADD45A	-0.023	0.19	-10000	0	-0.5	72	72
YWHAQ	0.021	0.002	-10000	0	-10000	0	0
FOXO1/14-3-3 family	0.024	0.064	0.18	1	-0.49	3	4
MST1	0.04	0.033	0.13	78	-10000	0	78
CSNK1D	0.02	0.004	-10000	0	-10000	0	0
CSNK1E	0.02	0.004	-10000	0	-10000	0	0
FOXO4/14-3-3 family	0.003	0.076	-10000	0	-0.5	6	6
YWHAB	0.02	0.004	-10000	0	-10000	0	0
MAPK8	0.027	0.05	0.19	60	-10000	0	60
MAPK9	0.04	0.063	0.19	104	-10000	0	104
YWHAG	0.017	0.008	-10000	0	-10000	0	0
YWHAE	0.021	0.002	-10000	0	-10000	0	0
YWHAZ	0.02	0.005	-10000	0	-10000	0	0
SIRT1	0.017	0.01	-10000	0	-0.031	1	1
SOD2	0.044	0.091	0.37	1	-0.43	3	4
RBL2	0.051	0.064	-10000	0	-0.56	2	2
RAL/GDP	0.03	0.014	-10000	0	-10000	0	0
CHUK	0.024	0.01	-10000	0	-10000	0	0
Ran/GTP	0.017	0.002	-10000	0	-10000	0	0
CSNK1G2	0.02	0.004	-10000	0	-10000	0	0
RAL/GTP	0.03	0.014	-10000	0	-10000	0	0
CSNK1G1	0.021	0.003	-10000	0	-10000	0	0
FASLG	0.028	0.02	-10000	0	-10000	0	0
SKP2	0.021	0.006	0.12	2	-10000	0	2
USP7	0.021	0.002	-10000	0	-10000	0	0
IKBKB	0.028	0.008	-10000	0	-10000	0	0
CCNB1	0.042	0.069	0.39	3	-10000	0	3
FOXO1-3a-4/beta catenin	0.065	0.071	0.26	24	-10000	0	24
proteasomal ubiquitin-dependent protein catabolic process	0.024	0.036	-10000	0	-10000	0	0
CSNK1A1	0.021	0.003	-10000	0	-10000	0	0
SGK1	0.027	0.009	-10000	0	-10000	0	0
CSNK1G3	0.021	0.002	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.03	0.004	-10000	0	-10000	0	0
ZFAND5	0.033	0.058	0.3	2	-10000	0	2
SFN	0.022	0.02	0.12	23	-10000	0	23
CDK2	0.053	0.048	0.12	198	-10000	0	198
FOXO3A/14-3-3	0.011	0.072	-10000	0	-0.48	5	5
CREBBP	0.022	0.004	-10000	0	-10000	0	0
FBXO32	0.055	0.086	0.51	3	-10000	0	3
BCL6	0.043	0.097	-10000	0	-0.62	9	9
RALB	0.021	0.001	-10000	0	-10000	0	0
RALA	0.018	0.008	-10000	0	-10000	0	0
YWHAH	0.02	0.005	-10000	0	-10000	0	0

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	0.013	0.035	-10000	0	-0.19	16	16
FZD6	0.021	0.012	0.12	7	-10000	0	7
WNT6	0.022	0.009	0.12	5	-10000	0	5
WNT4	0.019	0.009	0.12	2	-10000	0	2
FZD3	0.021	0.003	-10000	0	-10000	0	0
WNT5A	0.028	0.026	0.12	45	-10000	0	45
WNT11	0.022	0.01	0.12	6	-10000	0	6

×

Canonical NF-kappaB 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
FBXW11	0.021	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.024	0.049	0.19	5	-0.25	3	8
ERC1	0.02	0.005	-10000	0	-10000	0	0
RIP2/NOD2	0.047	0.033	0.11	155	-10000	0	155
NFKBIA	-0.012	0.025	0.2	8	-10000	0	8
BIRC2	0.021	0.003	-10000	0	-10000	0	0
IKBKB	0.021	0.003	-10000	0	-10000	0	0
RIPK2	0.02	0.007	0.12	2	-10000	0	2
IKBKG	0.015	0.031	-10000	0	-0.32	3	3
IKK complex/A20	0.041	0.052	0.22	1	-0.3	3	4
NEMO/A20/RIP2	0.02	0.007	0.12	2	-10000	0	2
XPO1	0.021	0.001	-10000	0	-10000	0	0
NEMO/ATM	0.03	0.039	-10000	0	-0.31	3	3
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.021	0.002	-10000	0	-10000	0	0
Exportin 1/RanGTP	0.028	0.003	-10000	0	-10000	0	0
IKK complex/ELKS	0.032	0.039	-10000	0	-0.29	3	3
BCL10/MALT1/TRAF6	0.036	0.016	-10000	0	-10000	0	0
NOD2	0.046	0.044	0.12	159	-10000	0	159
NFKB1	0.021	0.003	-10000	0	-10000	0	0
RELA	0.021	0.003	-10000	0	-10000	0	0
MALT1	0.02	0.004	-10000	0	-10000	0	0
cIAP1/UbcH5C	0.03	0.006	-10000	0	-10000	0	0
ATM	0.021	0.003	-10000	0	-10000	0	0
TNF/TNFR1A	0.019	0.049	-10000	0	-0.16	44	44
TRAF6	0.021	0.003	-10000	0	-10000	0	0
PRKCA	0.02	0.004	-10000	0	-10000	0	0
CHUK	0.019	0.006	-10000	0	-10000	0	0
UBE2D3	0.021	0.002	-10000	0	-10000	0	0
TNF	0.021	0.015	0.12	11	-10000	0	11
NF kappa B1 p50/RelA	0.044	0.01	-10000	0	-10000	0	0
BCL10	0.019	0.007	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.012	0.025	0.2	8	-10000	0	8
beta TrCP1/SCF ubiquitin ligase complex	0.021	0.003	-10000	0	-10000	0	0
TNFRSF1A	0.021	0.01	0.12	5	-10000	0	5
IKK complex	0.036	0.043	0.22	1	-0.3	3	4
CYLD	0.021	0.002	-10000	0	-10000	0	0
IKK complex/PKC alpha	0.045	0.041	0.22	1	-0.3	3	4

×

Arf6 trafficking events

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
SLC2A4	0.02	0.004	-10000	0	-10000	0	0
CLTC	0.011	0.06	-10000	0	-0.32	18	18
calcium ion-dependent exocytosis	0.014	0.034	-10000	0	-0.16	5	5
Dynamin 2/GTP	0.017	0.005	-10000	0	-10000	0	0
EXOC4	0.017	0.009	-10000	0	-10000	0	0
CD59	0.007	0.051	-10000	0	-0.26	19	19
CPE	-0.009	0.002	-10000	0	-10000	0	0
CTNNB1	0.021	0.002	-10000	0	-10000	0	0
membrane fusion	0.004	0.011	-10000	0	-0.19	1	1
CTNND1	-0.013	0.021	0.18	8	-10000	0	8
DNM2	0.02	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.009	0.036	0.13	5	-0.18	8	13
TSHR	0.031	0.036	0.063	370	-10000	0	370
INS	-0.005	0.092	-10000	0	-0.45	26	26
BIN1	0.021	0.001	-10000	0	-10000	0	0
mol:Choline	0.004	0.011	-10000	0	-0.19	1	1
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	-0.009	0.004	0.063	2	-10000	0	2
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.02	0.004	-10000	0	-10000	0	0
mol:Ca2+	0.017	0.005	-10000	0	-10000	0	0
JUP	0.007	0.052	-10000	0	-0.26	20	20
ASAP2/amphiphysin II	0.039	0.008	-10000	0	-10000	0	0
ARF6/GTP	0.015	0.003	-10000	0	-10000	0	0
CDH1	0.003	0.057	-10000	0	-0.27	20	20
clathrin-independent pinocytosis	0.015	0.003	-10000	0	-10000	0	0
MAPK8IP3	0.021	0.003	-10000	0	-10000	0	0
positive regulation of endocytosis	0.015	0.003	-10000	0	-10000	0	0
EXOC2	0.021	0.003	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.005	0.033	-10000	0	-0.21	8	8
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.021	0.002	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.02	0.054	0.25	18	-10000	0	18
positive regulation of phagocytosis	-0.009	0.004	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.026	0.016	-10000	0	-0.13	6	6
ACAP1	0.02	0.035	0.12	1	-0.15	5	6
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	-0.03	0.067	-10000	0	-0.35	10	10
clathrin heavy chain/ACAP1	0.015	0.054	0.18	11	-0.22	18	29
JIP4/KLC1	0.038	0.01	-10000	0	-10000	0	0
EXOC1	0.02	0.004	-10000	0	-10000	0	0
exocyst	0.005	0.033	-10000	0	-0.21	8	8
RALA/GTP	0.013	0.006	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.027	0.006	-10000	0	-10000	0	0
receptor recycling	0.015	0.003	-10000	0	-10000	0	0
CTNNA1	-0.013	0.02	0.18	7	-10000	0	7
NME1	-0.009	0.005	0.063	2	-10000	0	2
clathrin coat assembly	0.011	0.061	-10000	0	-0.31	19	19
IL2RA	0.009	0.049	-10000	0	-0.3	13	13
VAMP3	-0.009	0.004	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	0.019	0.051	-10000	0	-0.26	11	11
EXOC6	0.019	0.006	-10000	0	-10000	0	0
PLD1	0.004	0.023	-10000	0	-0.21	7	7
PLD2	0.006	0.007	-10000	0	-10000	0	0
EXOC5	0.02	0.004	-10000	0	-10000	0	0
PIP5K1C	0.009	0.033	-10000	0	-0.19	8	8
SDC1	0.008	0.052	-10000	0	-0.26	20	20
ARF6/GDP	0.018	0.004	-10000	0	-10000	0	0
EXOC7	0.02	0.004	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.022	0.055	-10000	0	-0.25	18	18
mol:Phosphatidic acid	0.004	0.011	-10000	0	-0.19	1	1
endocytosis	-0.038	0.008	-10000	0	-10000	0	0
SCAMP2	0.021	0.003	-10000	0	-10000	0	0
ADRB2	0.008	0.063	0.25	4	-0.3	20	24
EXOC3	0.021	0.003	-10000	0	-10000	0	0
ASAP2	0.021	0.002	-10000	0	-10000	0	0
Dynamin 2/GDP	0.02	0.006	-10000	0	-10000	0	0
KLC1	0.02	0.004	-10000	0	-10000	0	0
AVPR2	0.009	0.063	0.2	7	-0.3	19	26
RALA	0.018	0.008	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.015	0.053	-10000	0	-0.24	18	18

×

Insulin Pathway

Figure S108. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S108. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	0.032	0.022	-10000	0	-10000	0	0
TC10/GTP	0.031	0.02	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	0.049	0.017	-10000	0	-10000	0	0
HRAS	0.02	0.005	-10000	0	-10000	0	0
APS homodimer	0.02	0.02	0.12	20	-10000	0	20
GRB14	0.016	0.009	-10000	0	-10000	0	0
FOXO3	-0.018	0.14	-10000	0	-0.64	32	32
AKT1	-0.03	0.064	0.19	28	-10000	0	28
INSR	0.022	0.007	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.037	0.015	0.18	2	-10000	0	2
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.017	0.008	-10000	0	-10000	0	0
SORBS1	0.019	0.006	-10000	0	-10000	0	0
CRK	0.021	0.002	-10000	0	-10000	0	0
PTPN1	-0.007	0.026	0.16	15	-10000	0	15
CAV1	-0.001	0.034	0.18	9	-10000	0	9
CBL/APS/CAP/Crk-II/C3G	0.048	0.03	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1/NCK2	0.049	0.016	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.039	0.015	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.017	0.019	-10000	0	-0.39	1	1
RPS6KB1	-0.031	0.06	0.16	35	-10000	0	35
PARD6A	0.021	0.002	-10000	0	-10000	0	0
CBL	0.021	0.003	-10000	0	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.014	0.022	-10000	0	-0.51	1	1
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.04	0.045	0.13	14	-10000	0	14
HRAS/GTP	-0.021	0.015	-10000	0	-10000	0	0
Insulin Receptor	0.022	0.007	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.056	0.024	-10000	0	-10000	0	0
PRKCI	0.016	0.021	-10000	0	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.007	0.057	-10000	0	-0.11	138	138
SHC1	0.023	0.016	0.12	16	-10000	0	16
negative regulation of MAPKKK cascade	0.028	0.033	-10000	0	-0.42	1	1
PI3K	0.048	0.018	-10000	0	-10000	0	0
NCK2	0.021	0.001	-10000	0	-10000	0	0
RHOQ	0.021	0.001	-10000	0	-10000	0	0
mol:H2O2	-0.001	0.003	0.033	1	-10000	0	1
HRAS/GDP	0.015	0.003	-10000	0	-10000	0	0
AKT2	-0.031	0.055	0.18	21	-10000	0	21
PRKCZ	-0.061	0.16	-10000	0	-0.37	131	131
SH2B2	0.02	0.02	0.12	20	-10000	0	20
SHC/SHIP	-0.007	0.039	0.17	21	-10000	0	21
F2RL2	0.04	0.041	0.12	125	-10000	0	125
TRIP10	0.023	0.016	0.12	15	-10000	0	15
Insulin Receptor/Insulin/Shc	0.038	0.017	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.029	0.011	0.096	15	-10000	0	15
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.056	0.024	-10000	0	-10000	0	0
RAPGEF1	0.021	0.003	-10000	0	-10000	0	0
RASA1	0.021	0.002	-10000	0	-10000	0	0
NCK1	0.021	0.005	0.12	1	-10000	0	1
CBL/APS/CAP/Crk-II	0.043	0.027	-10000	0	-10000	0	0
TC10/GDP	0.016	0.001	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.042	0.025	-10000	0	-10000	0	0
INPP5D	-0.007	0.035	0.17	22	-10000	0	22
SOS1	0.021	0.001	-10000	0	-10000	0	0
SGK1	-0.023	0.15	-10000	0	-0.67	32	32
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.021	0.003	-10000	0	-10000	0	0
IRS1	0.021	0.001	-10000	0	-10000	0	0
p62DOK/RasGAP	0.029	0.033	-10000	0	-0.42	1	1
INS	0.018	0.01	0.08	9	-10000	0	9
mol:PI-3-4-P2	-0.007	0.035	0.16	22	-10000	0	22
GRB2	0.02	0.004	-10000	0	-10000	0	0
EIF4EBP1	-0.027	0.063	0.18	33	-10000	0	33
PTPRA	0.021	0.005	-10000	0	-10000	0	0
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
TC10/GTP/CIP4	0.029	0.011	0.096	15	-10000	0	15
PDPK1	0.021	0.002	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.014	0.021	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.037	0.013	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS3	0.028	0.013	-10000	0	-10000	0	0
Par3/Par6	0.059	0.028	0.17	6	-0.09	1	7

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	-0.011	0.005	-10000	0	-10000	0	0
SMARCC1	0.007	0.009	-10000	0	-10000	0	0
REL	0.021	0.006	0.12	1	-0.015	3	4
HDAC7	-0.01	0.028	0.16	8	-10000	0	8
JUN	0.018	0.008	-10000	0	-0.016	11	11
EP300	0.02	0.004	-10000	0	-10000	0	0
KAT2B	0.021	0.005	0.12	1	-10000	0	1
KAT5	0.021	0.003	-10000	0	-10000	0	0
MAPK14	-0.009	0.009	-10000	0	-10000	0	0
FOXO1	0.02	0.004	-10000	0	-10000	0	0
T-DHT/AR	0.028	0.033	0.19	9	-10000	0	9
MAP2K6	0.021	0.004	-10000	0	-10000	0	0
BRM/BAF57	0.028	0.013	-10000	0	-10000	0	0
MAP2K4	0.021	0.002	-10000	0	-10000	0	0
SMARCA2	0.019	0.009	-10000	0	-0.032	11	11
PDE9A	0.02	0.029	-10000	0	-0.46	2	2
NCOA2	0.02	0.005	-10000	0	-10000	0	0
CEBPA	0.019	0.011	0.12	4	-10000	0	4
EHMT2	0.02	0.005	-10000	0	-0.018	11	11
cell proliferation	0.012	0.07	0.25	23	-0.38	2	25
NR0B1	0.028	0.029	0.12	54	-10000	0	54
EGR1	0.02	0.01	0.12	2	-0.027	12	14
RXRs/9cRA	0.029	0.039	-10000	0	-0.12	40	40
AR/RACK1/Src	0.003	0.047	0.16	38	-10000	0	38
AR/GR	0.025	0.034	0.18	3	-0.19	2	5
GNB2L1	0.023	0.016	0.12	15	-10000	0	15
PKN1	0.02	0.004	-10000	0	-10000	0	0
RCHY1	0.021	0.003	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0.001	-10000	0	-10000	0	0
MAPK8	-0.008	0.01	0.028	1	-10000	0	1
T-DHT/AR/TIF2/CARM1	0.023	0.042	0.18	22	-0.22	5	27
SRC	-0.017	0.012	-10000	0	-0.12	5	5
NR3C1	0.021	0.002	-10000	0	-10000	0	0
KLK3	-0.048	0.16	-10000	0	-1.1	12	12
APPBP2	0.021	0.004	-10000	0	-10000	0	0
TRIM24	0.016	0.01	-10000	0	-0.03	10	10
T-DHT/AR/TIP60	0.004	0.038	0.18	21	-10000	0	21
TMPRSS2	0.023	0.041	-10000	0	-0.47	3	3
RXRG	0.019	0.008	0.12	1	-0.018	10	11
mol:9cRA	0	0.001	-10000	0	-10000	0	0
RXRA	0.02	0.006	-10000	0	-0.018	10	10
RXRB	0.02	0.005	-10000	0	-0.018	10	10
CARM1	0.02	0.004	-10000	0	-10000	0	0
NR2C2	0.021	0.002	-10000	0	-10000	0	0
KLK2	0.009	0.044	0.25	3	-0.24	5	8
AR	0.016	0.03	0.16	18	-10000	0	18
SENP1	0.02	0.006	-10000	0	-0.018	9	9
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
MDM2	0.019	0.009	-10000	0	-0.018	22	22
SRY	0	0.004	0.03	12	-10000	0	12
GATA2	0.021	0.008	0.12	4	-10000	0	4
MYST2	0	0.001	-10000	0	-10000	0	0
HOXB13	0.042	0.047	0.12	152	-0.044	12	164
T-DHT/AR/RACK1/Src	0.004	0.052	0.17	47	-10000	0	47
positive regulation of transcription	0.021	0.008	0.12	4	-10000	0	4
DNAJA1	0.021	0.005	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.009	0.004	-10000	0	-10000	0	0
NCOA1	0.021	0.013	0.13	1	-10000	0	1
SPDEF	0.018	0.009	-10000	0	-0.032	9	9
T-DHT/AR/TIF2	0.002	0.055	0.18	2	-0.22	16	18
T-DHT/AR/Hsp90	0.004	0.036	0.18	19	-10000	0	19
GSK3B	0.021	0.003	-10000	0	-10000	0	0
NR2C1	0.021	0.003	-10000	0	-10000	0	0
mol:T-DHT	-0.014	0.011	-10000	0	-0.12	3	3
SIRT1	0.019	0.006	-10000	0	-10000	0	0
ZMIZ2	0.017	0.011	-10000	0	-0.018	2	2
POU2F1	0.028	0.013	0.14	3	-10000	0	3
T-DHT/AR/DAX-1	0.011	0.045	0.19	24	-10000	0	24
CREBBP	0.021	0.002	-10000	0	-10000	0	0
SMARCE1	0.02	0.007	-10000	0	-0.032	12	12

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.02	0.037	-10000	0	-10000	0	0
epithelial cell differentiation	-0.008	0.053	-10000	0	-10000	0	0
ITCH	0.018	0.015	-10000	0	-10000	0	0
WWP1	0.009	0.043	-10000	0	-10000	0	0
FYN	0.02	0.004	-10000	0	-10000	0	0
EGFR	0.053	0.054	0.12	235	-10000	0	235
PRL	0.017	0.009	0.12	4	-10000	0	4
neuron projection morphogenesis	-0.02	0.067	0.26	15	-10000	0	15
PTPRZ1	0.028	0.034	0.12	70	-10000	0	70
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.014	0.063	-10000	0	-10000	0	0
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	0.004	0.032	-10000	0	-10000	0	0
ADAM17	0.018	0.015	-10000	0	-10000	0	0
ErbB4/ErbB4	0.006	0.031	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	0.015	0.045	-10000	0	-0.24	1	1
NCOR1	0.021	0.002	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.002	0.053	-10000	0	-10000	0	0
GRIN2B	-0.032	0.073	0.22	6	-0.24	7	13
ErbB4/ErbB2/betacellulin	0.024	0.032	-10000	0	-10000	0	0
STAT1	0.022	0.011	0.12	7	-10000	0	7
HBEGF	0.021	0.003	-10000	0	-10000	0	0
PRLR	0.021	0.008	0.12	3	-10000	0	3
E4ICDs/ETO2	0.017	0.043	-10000	0	-0.24	1	1
axon guidance	-0.018	0.045	-10000	0	-10000	0	0
NEDD4	0.034	0.036	0.13	81	-10000	0	81
Prolactin receptor/Prolactin receptor/Prolactin	0.025	0.023	0.11	4	-0.16	9	13
CBFA2T3	0.02	0.005	-10000	0	-10000	0	0
ErbB4/ErbB2/HBEGF	0.022	0.028	-10000	0	-10000	0	0
MAPK3	-0.019	0.062	0.22	12	-10000	0	12
STAT1 (dimer)	0.021	0.038	-10000	0	-10000	0	0
MAPK1	-0.018	0.061	0.22	12	-10000	0	12
JAK2	0.02	0.005	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.012	0.049	-10000	0	-10000	0	0
NRG1	-0.009	0.01	-10000	0	-10000	0	0
NRG3	0.017	0.008	-10000	0	-10000	0	0
NRG2	0.021	0.003	-10000	0	-10000	0	0
NRG4	0.018	0.007	-10000	0	-10000	0	0
heart development	-0.018	0.045	-10000	0	-10000	0	0
neural crest cell migration	-0.012	0.048	-10000	0	-10000	0	0
ERBB2	-0.01	0.012	0.05	8	-10000	0	8
WWOX/E4ICDs	0.02	0.037	-10000	0	-10000	0	0
SHC1	0.023	0.016	0.12	16	-10000	0	16
ErbB4/EGFR/neuregulin 4	0.035	0.063	-10000	0	-10000	0	0
apoptosis	0.005	0.093	0.3	53	-10000	0	53
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	0.02	0.038	-10000	0	-0.24	1	1
ErbB4/ErbB2/epiregulin	0.022	0.03	-10000	0	-10000	0	0
ErbB4/ErbB4/betacellulin/betacellulin	0.022	0.04	-10000	0	-10000	0	0
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.043	0.045	-10000	0	-10000	0	0
MDM2	0.006	0.046	0.24	16	-10000	0	16
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.005	0.05	-10000	0	-10000	0	0
STAT5A	-0.022	0.048	0.24	1	-10000	0	1
ErbB4/EGFR/neuregulin 1 beta	0.018	0.062	0.22	1	-10000	0	1
DLG4	0.021	0.002	-10000	0	-10000	0	0
GRB2/SHC	0.031	0.013	0.11	14	-10000	0	14
E4ICDs/TAB2/NCoR1	0.018	0.034	-10000	0	-10000	0	0
STAT5A (dimer)	0.001	0.061	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.012	0.057	0.28	1	-10000	0	1
LRIG1	0.021	0.005	0.12	1	-10000	0	1
EREG	0.023	0.018	0.12	19	-10000	0	19
BTC	0.024	0.022	0.12	30	-10000	0	30
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.018	0.045	-10000	0	-10000	0	0
ERBB4	0.006	0.031	-10000	0	-10000	0	0
STAT5B	0.021	0.002	-10000	0	-10000	0	0
YAP1	0.013	0.01	-10000	0	-10000	0	0
GRB2	0.02	0.004	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0.018	0.032	-10000	0	-10000	0	0
glial cell differentiation	-0.018	0.034	-10000	0	-10000	0	0
WWOX	0.021	0.003	-10000	0	-10000	0	0
cell proliferation	-0.029	0.068	0.31	2	-0.29	1	3

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.015	0.027	-10000	0	-10000	0	0
regulation of axonogenesis	-0.001	0.043	0.25	19	-10000	0	19
myoblast fusion	-0.011	0.029	0.34	1	-10000	0	1
mol:GTP	0.016	0.03	-10000	0	-0.16	16	16
regulation of calcium-dependent cell-cell adhesion	-0.034	0.03	0.11	6	-10000	0	6
ARF1/GTP	0.028	0.028	-10000	0	-0.12	21	21
mol:GM1	0.005	0.022	-10000	0	-0.12	18	18
mol:Choline	-0.006	0.019	-10000	0	-0.1	18	18
lamellipodium assembly	0.003	0.048	-10000	0	-0.38	8	8
MAPK3	0.016	0.023	-10000	0	-0.12	1	1
ARF6/GTP/NME1/Tiam1	0.034	0.031	-10000	0	-0.11	6	6
ARF1	0.021	0.002	-10000	0	-10000	0	0
ARF6/GDP	0.011	0.03	-10000	0	-0.34	1	1
ARF1/GDP	0.009	0.05	-10000	0	-0.23	17	17
ARF6	0.028	0.007	-10000	0	-10000	0	0
RAB11A	0.021	0.003	-10000	0	-10000	0	0
TIAM1	0.017	0.012	-10000	0	-0.031	1	1
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.016	0.022	-10000	0	-0.12	1	1
actin filament bundle formation	-0.013	0.049	0.23	16	-10000	0	16
KALRN	0.008	0.016	-10000	0	-10000	0	0
RAB11FIP3/RAB11A	0.031	0.005	-10000	0	-10000	0	0
RhoA/GDP	0.013	0.049	-10000	0	-0.23	16	16
NME1	0.018	0.014	0.13	2	-10000	0	2
Rac1/GDP	0.013	0.042	-10000	0	-0.25	9	9
substrate adhesion-dependent cell spreading	0.016	0.03	-10000	0	-0.16	16	16
cortical actin cytoskeleton organization	0.003	0.049	-10000	0	-0.38	8	8
RAC1	0.018	0.008	-10000	0	-10000	0	0
liver development	0.016	0.03	-10000	0	-0.16	16	16
ARF6/GTP	0.016	0.03	-10000	0	-0.16	16	16
RhoA/GTP	0.028	0.027	-10000	0	-0.12	18	18
mol:GDP	0.004	0.044	-10000	0	-0.25	16	16
ARF6/GTP/RAB11FIP3/RAB11A	0.039	0.028	-10000	0	-0.11	19	19
RHOA	0.021	0.003	-10000	0	-10000	0	0
PLD1	0.011	0.024	-10000	0	-0.12	19	19
RAB11FIP3	0.021	0.002	-10000	0	-10000	0	0
tube morphogenesis	0.003	0.048	-10000	0	-0.38	8	8
ruffle organization	0.001	0.043	-10000	0	-0.25	19	19
regulation of epithelial cell migration	0.016	0.03	-10000	0	-0.16	16	16
PLD2	0.011	0.024	-10000	0	-0.12	20	20
PIP5K1A	0.001	0.043	-10000	0	-0.25	19	19
mol:Phosphatidic acid	-0.006	0.019	-10000	0	-0.1	18	18
Rac1/GTP	0.003	0.049	-10000	0	-0.39	8	8

×

IL27-mediated signaling events

Figure S112. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S112. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.019	0.008	-10000	0	-10000	0	0
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.016	0.055	0.33	2	-10000	0	2
IL27/IL27R/JAK1	-0.039	0.061	-10000	0	-10000	0	0
TBX21	-0.084	0.086	0.33	3	-0.31	1	4
IL12B	0.017	0.007	0.13	2	-10000	0	2
IL12A	-0.005	0.007	0.05	11	-10000	0	11
IL6ST	0	0.019	-10000	0	-10000	0	0
IL27RA/JAK1	-0.006	0.04	-10000	0	-10000	0	0
IL27	0.005	0.032	0.12	33	-10000	0	33
TYK2	0.019	0.004	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.006	0.11	0.38	1	-0.47	1	2
T-helper 2 cell differentiation	0.016	0.055	0.33	2	-10000	0	2
T cell proliferation during immune response	0.016	0.055	0.33	2	-10000	0	2
MAPKKK cascade	-0.016	0.055	-10000	0	-0.33	2	2
STAT3	0.021	0.002	-10000	0	-10000	0	0
STAT2	0.021	0.003	-10000	0	-10000	0	0
STAT1	0.012	0.019	0.12	7	-0.02	136	143
IL12RB1	0.021	0.006	0.12	1	-10000	0	1
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.15	0.12	-10000	0	-0.34	10	10
IL27/IL27R/JAK2/TYK2	-0.016	0.056	-10000	0	-0.34	2	2
positive regulation of T cell mediated cytotoxicity	-0.016	0.055	-10000	0	-0.33	2	2
STAT1 (dimer)	-0.093	0.1	-10000	0	-10000	0	0
JAK2	0.019	0.005	-10000	0	-10000	0	0
JAK1	0.008	0.016	-10000	0	-0.02	142	142
STAT2 (dimer)	-0.013	0.058	-10000	0	-0.32	2	2
T cell proliferation	-0.019	0.052	-10000	0	-0.33	1	1
IL12/IL12R/TYK2/JAK2	0.006	0.097	-10000	0	-0.8	9	9
IL17A	-0.006	0.11	-10000	0	-10000	0	0
mast cell activation	0.016	0.055	0.33	2	-10000	0	2
IFNG	-0.001	0.02	-10000	0	-0.1	11	11
T cell differentiation	-0.004	0.003	-10000	0	-0.014	7	7
STAT3 (dimer)	-0.013	0.059	-10000	0	-0.32	2	2
STAT5A (dimer)	-0.013	0.059	-10000	0	-0.32	2	2
STAT4 (dimer)	-0.018	0.075	-10000	0	-0.33	8	8
STAT4	0.009	0.01	-10000	0	-10000	0	0
T cell activation	-0.002	0.003	-10000	0	-0.041	1	1
IL27R/JAK2/TYK2	-0.01	0.045	-10000	0	-10000	0	0
GATA3	0.034	0.12	0.66	22	-10000	0	22
IL18	-0.004	0.011	0.05	29	-10000	0	29
positive regulation of mast cell cytokine production	-0.013	0.058	-10000	0	-0.31	2	2
IL27/EBI3	0.007	0.034	0.18	1	-10000	0	1
IL27RA	-0.003	0.028	-10000	0	-10000	0	0
IL6	0.017	0.019	-10000	0	-10000	0	0
STAT5A	0.021	0.002	-10000	0	-10000	0	0
monocyte differentiation	0	0	-10000	0	-10000	0	0
IL2	-0.006	0.02	-10000	0	-10000	0	0
IL1B	-0.005	0.005	0.05	4	-10000	0	4
EBI3	0.001	0.022	0.12	5	-10000	0	5
TNF	-0.005	0.007	0.05	11	-10000	0	11

×

Angiopoietin receptor Tie2-mediated signaling

Figure S113. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S113. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.037	0.09	-10000	0	-0.74	5	5
NCK1/PAK1/Dok-R	-0.017	0.044	-10000	0	-0.39	5	5
NCK1/Dok-R	0.029	0.092	-10000	0	-0.82	5	5
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
mol:beta2-estradiol	-0.003	0.018	0.24	3	-10000	0	3
RELA	0.021	0.003	-10000	0	-10000	0	0
SHC1	0.024	0.016	0.13	16	-10000	0	16
Rac/GDP	0.013	0.006	-10000	0	-10000	0	0
F2	-0.011	0.026	0.17	4	-0.067	1	5
TNIP2	0.021	0.009	0.12	5	-10000	0	5
NF kappa B/RelA	0.034	0.09	-10000	0	-0.78	5	5
FN1	0.036	0.036	0.12	94	-10000	0	94
PLD2	0.008	0.082	-10000	0	-0.84	5	5
PTPN11	0.021	0.003	-10000	0	-10000	0	0
GRB14	0.016	0.009	-10000	0	-10000	0	0
ELK1	0.002	0.081	-10000	0	-0.79	5	5
GRB7	0.02	0.009	0.12	4	-10000	0	4
PAK1	0.015	0.009	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	0.046	0.1	-10000	0	-0.77	5	5
CDKN1A	0.051	0.084	-10000	0	-0.53	5	5
ITGA5	0.034	0.036	0.12	89	-10000	0	89
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	0.029	0.092	-10000	0	-0.82	5	5
CRK	0.021	0.002	-10000	0	-10000	0	0
mol:NO	0.068	0.11	0.34	11	-0.55	5	16
PLG	0.007	0.082	-10000	0	-0.84	5	5
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.033	0.083	-10000	0	-0.68	5	5
GRB2	0.02	0.004	-10000	0	-10000	0	0
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
ANGPT2	0.051	0.069	-10000	0	-0.48	1	1
BMX	0.007	0.083	-10000	0	-0.84	5	5
ANGPT1	0.005	0.073	-10000	0	-1.1	2	2
tube development	0.04	0.082	-10000	0	-0.59	5	5
ANGPT4	0.036	0.037	0.13	92	-10000	0	92
response to hypoxia	0	0.007	0.037	3	-0.059	5	8
Tie2/Ang1/GRB14	0.007	0.094	-10000	0	-0.86	5	5
alpha5/beta1 Integrin	0.037	0.031	0.18	10	-10000	0	10
FGF2	0.019	0.006	0.12	1	-0.016	8	9
STAT5A (dimer)	0.06	0.095	-10000	0	-0.65	5	5
mol:L-citrulline	0.068	0.11	0.34	11	-0.55	5	16
AGTR1	0.029	0.025	0.13	37	-10000	0	37
MAPK14	0.027	0.098	-10000	0	-0.85	6	6
Tie2/SHP2	-0.001	0.11	-10000	0	-0.76	6	6
TEK	-0.001	0.11	-10000	0	-0.82	6	6
RPS6KB1	0.038	0.091	-10000	0	-0.72	5	5
Angiotensin II/AT1	0.027	0.021	0.1	37	-10000	0	37
Tie2/Ang1/GRB2	0.017	0.09	-10000	0	-0.86	5	5
MAPK3	0.002	0.078	-10000	0	-0.79	5	5
MAPK1	0.003	0.078	-10000	0	-0.79	5	5
Tie2/Ang1/GRB7	0.016	0.091	-10000	0	-0.86	5	5
NFKB1	0.021	0.002	-10000	0	-10000	0	0
MAPK8	0.006	0.083	-10000	0	-0.84	5	5
PI3K	0.039	0.094	-10000	0	-0.82	5	5
FES	0.025	0.098	-10000	0	-0.89	5	5
Crk/Dok-R	0.029	0.092	-10000	0	-0.82	5	5
Tie2/Ang1/ABIN2	0.018	0.091	-10000	0	-0.85	5	5
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.039	0.085	-10000	0	-0.67	5	5
STAT5A	0.021	0.002	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.045	0.099	0.38	3	-0.69	5	8
Tie2/Ang2	0.046	0.095	-10000	0	-0.75	5	5
Tie2/Ang1	0.014	0.087	-10000	0	-0.88	5	5
FOXO1	0.04	0.086	0.37	1	-0.67	5	6
ELF1	0.025	0.012	-10000	0	-0.11	2	2
ELF2	0.011	0.081	-10000	0	-0.82	5	5
mol:Choline	0.008	0.08	-10000	0	-0.81	5	5
cell migration	-0.003	0.031	0.092	2	-0.21	5	7
FYN	0.04	0.086	-10000	0	-0.66	5	5
DOK2	0.026	0.024	0.12	36	-10000	0	36
negative regulation of cell cycle	0.05	0.081	-10000	0	-0.49	5	5
ETS1	0.026	0.028	0.13	22	-0.25	3	25
PXN	0.043	0.093	0.4	4	-0.59	5	9
ITGB1	0.021	0.016	0.12	12	-10000	0	12
NOS3	0.065	0.11	0.36	9	-0.61	5	14
RAC1	0.018	0.008	-10000	0	-10000	0	0
TNF	0.024	0.028	0.13	11	-0.31	3	14
MAPKKK cascade	0.008	0.08	-10000	0	-0.81	5	5
RASA1	0.021	0.002	-10000	0	-10000	0	0
Tie2/Ang1/Shc	0.02	0.09	-10000	0	-0.82	5	5
NCK1	0.021	0.005	0.12	1	-10000	0	1
vasculogenesis	0.068	0.1	0.3	24	-0.49	5	29
mol:Phosphatidic acid	0.008	0.08	-10000	0	-0.81	5	5
mol:Angiotensin II	0.003	0.003	-10000	0	-10000	0	0
mol:NADP	0.068	0.11	0.34	11	-0.55	5	16
Rac1/GTP	0.036	0.08	-10000	0	-0.65	5	5
MMP2	0.009	0.084	-10000	0	-0.84	5	5

×

mTOR signaling pathway

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
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.019	0.006	-10000	0	-10000	0	0
mol:PIP3	-0.006	0.013	-10000	0	-0.17	2	2
FRAP1	0.022	0.047	0.24	6	-0.31	1	7
AKT1	0.009	0.048	0.16	56	-0.16	2	58
INSR	0.021	0.003	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.023	0.007	0.096	1	-10000	0	1
mol:GTP	0.028	0.046	0.16	42	-10000	0	42
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0.009	0.016	-10000	0	-0.18	1	1
TSC2	0.021	0.002	-10000	0	-10000	0	0
RHEB/GDP	0.01	0.02	-10000	0	-0.12	1	1
TSC1	0.021	0.004	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.019	0.013	-10000	0	-0.19	2	2
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.018	0.022	-10000	0	-0.2	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.019	0.007	-10000	0	-10000	0	0
RPS6KB1	0.026	0.058	0.22	21	-0.33	1	22
MAP3K5	-0.006	0.041	0.17	2	-0.19	31	33
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
apoptosis	-0.006	0.041	0.17	2	-0.19	31	33
mol:LY294002	0	0	-10000	0	-0.001	2	2
EIF4B	0.022	0.058	0.22	25	-0.3	1	26
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.027	0.034	0.18	3	-0.27	1	4
eIF4E/eIF4G1/eIF4A1	0.013	0.019	-10000	0	-0.21	1	1
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.033	0.016	0.13	1	-0.18	2	3
mTOR/RHEB/GTP/Raptor/GBL	0	0.029	0.12	26	-10000	0	26
FKBP1A	0.02	0.004	-10000	0	-10000	0	0
RHEB/GTP	0.019	0.029	0.14	4	-10000	0	4
mol:Amino Acids	0	0	-10000	0	-0.001	2	2
FKBP12/Rapamycin	0.015	0.004	-10000	0	-10000	0	0
PDPK1	-0.009	0.016	0.18	2	-0.16	2	4
EIF4E	0.021	0.002	-10000	0	-10000	0	0
ASK1/PP5C	0.006	0.12	-10000	0	-0.53	32	32
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.005	0.03	-10000	0	-0.24	9	9
TSC1/TSC2	0.032	0.053	0.18	45	-10000	0	45
tumor necrosis factor receptor activity	0	0	0.001	2	-10000	0	2
RPS6	0.021	0.015	0.12	11	-10000	0	11
PPP5C	0.019	0.007	-10000	0	-10000	0	0
EIF4G1	0.021	0.003	-10000	0	-10000	0	0
IRS1	0.006	0.013	-10000	0	-0.21	2	2
INS	0.015	0.005	0.12	1	-10000	0	1
PTEN	0.018	0.007	-10000	0	-10000	0	0
PDK2	-0.009	0.015	0.18	2	-0.16	1	3
EIF4EBP1	0.047	0.095	-10000	0	-1	4	4
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
PPP2R5D	0.018	0.046	0.22	8	-0.29	1	9
peptide biosynthetic process	-0.013	0.004	-10000	0	-10000	0	0
RHEB	0.017	0.009	-10000	0	-10000	0	0
EIF4A1	0.021	0.002	-10000	0	-10000	0	0
mol:Rapamycin	0	0.001	0.002	61	-10000	0	61
EEF2	-0.013	0.004	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.047	0.084	-10000	0	-0.93	4	4

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.03	0.019	-10000	0	-10000	0	0
FBXW11	0.021	0.003	-10000	0	-10000	0	0
NF kappa B1 p50/c-Rel	0.019	0.011	0.094	1	-0.13	3	4
NF kappa B1 p50/RelA/I kappa B alpha	0.017	0.047	0.17	1	-0.18	10	11
NFKBIA	0.01	0.014	0.13	5	-10000	0	5
MAPK14	0.021	0.002	-10000	0	-10000	0	0
NF kappa B1 p105/p50	0.02	0.004	-10000	0	-10000	0	0
ARRB2	0.009	0.001	-10000	0	-10000	0	0
REL	0.021	0.005	0.12	1	-10000	0	1
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	0.021	0.019	0.099	29	-10000	0	29
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	0.02	0.004	-10000	0	-10000	0	0
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
NF kappa B1 p50 dimer	0.013	0.003	-10000	0	-10000	0	0
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
NFKB1	-0.012	0.002	-10000	0	-10000	0	0
RELA	0.021	0.003	-10000	0	-10000	0	0
positive regulation of anti-apoptosis	0.009	0.04	0.12	1	-0.19	2	3
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.018	0.047	0.17	1	-0.18	11	12
SRC	0.02	0.004	-10000	0	-10000	0	0
PI3K	0.03	0.006	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.006	0.037	0.12	1	-0.18	1	2
IKBKB	0.021	0.003	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.021	0.003	-10000	0	-10000	0	0
SYK	0.022	0.013	0.12	10	-10000	0	10
I kappa B alpha/PIK3R1	0.015	0.047	0.18	1	-0.18	11	12
cell death	0.017	0.046	0.16	1	-0.18	11	12
NF kappa B1 p105/c-Rel	0.019	0.011	0.094	1	-0.13	3	4
LCK	0.039	0.042	0.12	129	-10000	0	129
BCL3	0.023	0.023	0.12	29	-10000	0	29

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.02	0.004	-10000	0	-10000	0	0
Caspase 8 (4 units)	0.024	0.048	0.21	1	-0.22	2	3
NEF	0.001	0.004	-10000	0	-10000	0	0
NFKBIA	0.02	0.016	0.13	3	-0.073	13	16
BIRC3	-0.017	0.041	0.098	15	-0.28	13	28
CYCS	0.002	0.026	0.18	10	-10000	0	10
RIPK1	0.021	0.003	-10000	0	-10000	0	0
CD247	0.022	0.005	-10000	0	-10000	0	0
MAP2K7	0.013	0.077	-10000	0	-0.54	5	5
protein ubiquitination	0.011	0.053	0.2	9	-0.38	2	11
CRADD	0.021	0.002	-10000	0	-10000	0	0
DAXX	0.021	0.002	-10000	0	-10000	0	0
FAS	0.023	0.021	0.12	25	-10000	0	25
BID	0.008	0.02	0.17	5	-10000	0	5
NF-kappa-B/RelA/I kappa B alpha	0.04	0.033	0.17	1	-0.17	13	14
TRADD	0.021	0.002	-10000	0	-10000	0	0
MAP3K5	0.02	0.005	-10000	0	-10000	0	0
CFLAR	0.021	0.001	-10000	0	-10000	0	0
FADD	0.021	0.003	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.041	0.033	0.17	1	-0.17	13	14
MAPK8	0.013	0.068	-10000	0	-0.48	5	5
APAF1	0.021	0.002	-10000	0	-10000	0	0
TRAF1	0.021	0.003	-10000	0	-10000	0	0
TRAF2	0.021	0.003	-10000	0	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.013	0.016	0.22	1	-10000	0	1
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.005	0.049	-10000	0	-0.48	2	2
CHUK	0.011	0.055	0.2	9	-0.41	2	11
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.058	0.03	0.18	7	-10000	0	7
TCRz/NEF	0.016	0.021	-10000	0	-0.15	9	9
TNF	0.021	0.015	0.12	11	-10000	0	11
FASLG	0.005	0.024	-10000	0	-0.13	7	7
NFKB1	0.02	0.013	-10000	0	-0.074	11	11
TNFR1A/BAG4/TNF-alpha	0.028	0.049	-10000	0	-0.14	49	49
CASP6	0.025	0.077	-10000	0	-0.45	10	10
CASP7	-0.004	0.083	0.26	6	-0.32	23	29
RELA	0.02	0.013	-10000	0	-0.073	13	13
CASP2	0.017	0.009	-10000	0	-10000	0	0
CASP3	0	0.074	0.26	6	-0.37	15	21
TNFRSF1A	0.021	0.01	0.12	5	-10000	0	5
TNFR1A/BAG4	0.027	0.022	-10000	0	-0.16	7	7
CASP8	0.025	0.019	0.12	23	-10000	0	23
CASP9	0.019	0.008	0.12	1	-10000	0	1
MAP3K14	0.013	0.055	-10000	0	-0.37	3	3
APAF-1/Caspase 9	0.003	0.043	0.14	8	-0.2	11	19
BCL2	0.006	0.067	0.24	1	-0.46	4	5

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.019	0.007	-10000	0	-10000	0	0
SPHK1	0.021	0.011	0.12	6	-10000	0	6
GNAI2	0.021	0.003	-10000	0	-10000	0	0
mol:S1P	0.008	0.004	-10000	0	-10000	0	0
GNAO1	0.021	0.003	-10000	0	-10000	0	0
mol:Sphinganine-1-P	-0.01	0.007	0.051	6	-10000	0	6
growth factor activity	0	0	-10000	0	-10000	0	0
S1P/S1P2/G12/G13	0.027	0.043	-10000	0	-0.19	2	2
GNAI3	0.019	0.008	0.12	1	-10000	0	1
G12/G13	0.026	0.012	-10000	0	-10000	0	0
S1PR3	0.04	0.04	0.12	122	-10000	0	122
S1PR2	0.024	0.019	0.12	21	-10000	0	21
EDG1	0	0	-10000	0	-10000	0	0
S1P1/S1P	-0.004	0.033	-10000	0	-0.24	2	2
S1PR5	0.017	0.008	-10000	0	-10000	0	0
S1PR4	0.021	0.011	0.12	6	-10000	0	6
GNAI1	0.017	0.008	-10000	0	-10000	0	0
S1P/S1P5/G12	0.004	0.057	-10000	0	-0.19	15	15
S1P/S1P3/Gq	0.017	0.049	-10000	0	-0.35	8	8
S1P/S1P4/Gi	0.007	0.065	0.14	1	-0.28	8	9
GNAQ	0.021	0.003	-10000	0	-10000	0	0
GNAZ	0.02	0.004	-10000	0	-10000	0	0
GNA14	0.021	0.003	-10000	0	-10000	0	0
GNA15	0.021	0.006	0.12	1	-10000	0	1
GNA12	0.018	0.008	-10000	0	-10000	0	0
GNA13	0.02	0.004	-10000	0	-10000	0	0
GNA11	0.02	0.004	-10000	0	-10000	0	0
ABCC1	0.021	0.004	0.12	1	-10000	0	1

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.019	0.006	-10000	0	-10000	0	0
HDAC2	0.02	0.004	-10000	0	-10000	0	0
GNB1/GNG2	0.036	0.031	-10000	0	-0.12	1	1
forebrain development	0.034	0.082	0.32	5	-0.42	4	9
GNAO1	0.021	0.003	-10000	0	-10000	0	0
SMO/beta Arrestin2	0.032	0.027	0.11	63	-10000	0	63
SMO	0.027	0.033	0.12	64	-10000	0	64
ARRB2	0.021	0.002	-10000	0	-10000	0	0
GLI3/SPOP	0.007	0.061	-10000	0	-0.34	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
GSK3B	0.021	0.003	-10000	0	-10000	0	0
GNAI2	0.021	0.003	-10000	0	-10000	0	0
SIN3/HDAC complex	0.048	0.017	-10000	0	-10000	0	0
GNAI1	0.017	0.008	-10000	0	-10000	0	0
XPO1	0.022	0.002	-10000	0	-10000	0	0
GLI1/Su(fu)	0.021	0.052	-10000	0	-0.75	1	1
SAP30	0.02	0.006	0.12	1	-10000	0	1
mol:GDP	0.027	0.033	0.12	64	-10000	0	64
MIM/GLI2A	0.019	0.007	0.12	1	-10000	0	1
IFT88	0.02	0.005	-10000	0	-10000	0	0
GNAI3	0.019	0.008	0.12	1	-10000	0	1
GLI2	0.016	0.035	0.18	6	-0.24	1	7
GLI3	-0.001	0.06	-10000	0	-0.36	6	6
CSNK1D	0.02	0.004	-10000	0	-10000	0	0
CSNK1E	0.02	0.004	-10000	0	-10000	0	0
SAP18	0.02	0.005	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.02	0.005	-10000	0	-10000	0	0
GNG2	0.02	0.004	-10000	0	-10000	0	0
Gi family/GTP	0.004	0.04	-10000	0	-0.21	7	7
SIN3B	0.02	0.004	-10000	0	-10000	0	0
SIN3A	0.021	0.003	-10000	0	-10000	0	0
GLI3/Su(fu)	0.008	0.056	-10000	0	-0.41	6	6
GLI2/Su(fu)	0.016	0.04	-10000	0	-0.38	3	3
FOXA2	0.016	0.058	-10000	0	-0.61	3	3
neural tube patterning	0.034	0.082	0.32	5	-0.42	4	9
SPOP	0.021	0.002	-10000	0	-10000	0	0
Su(fu)/PIAS1	0.031	0.04	-10000	0	-0.16	1	1
GNB1	0.019	0.007	-10000	0	-10000	0	0
CSNK1G2	0.02	0.004	-10000	0	-10000	0	0
CSNK1G3	0.021	0.002	-10000	0	-10000	0	0
MTSS1	0.019	0.007	0.12	1	-10000	0	1
embryonic limb morphogenesis	0.034	0.082	0.32	5	-0.42	4	9
SUFU	0.014	0.01	-10000	0	-10000	0	0
LGALS3	0.028	0.028	0.12	49	-10000	0	49
catabolic process	0.025	0.065	0.23	2	-0.47	4	6
GLI3A/CBP	0.017	0.05	0.12	2	-0.27	19	21
KIF3A	0.021	0.003	-10000	0	-10000	0	0
GLI1	0.034	0.083	0.34	4	-0.44	4	8
RAB23	0.021	0.002	-10000	0	-10000	0	0
CSNK1A1	0.021	0.003	-10000	0	-10000	0	0
IFT172	0.021	0.002	-10000	0	-10000	0	0
RBBP7	0.021	0.002	-10000	0	-10000	0	0
Su(fu)/Galectin3	0.036	0.044	0.17	13	-0.16	1	14
GNAZ	0.021	0.004	-10000	0	-10000	0	0
RBBP4	0.019	0.006	-10000	0	-10000	0	0
CSNK1G1	0.021	0.003	-10000	0	-10000	0	0
PIAS1	0.021	0.003	-10000	0	-10000	0	0
PRKACA	0.02	0.004	-10000	0	-10000	0	0
GLI2/SPOP	0.025	0.041	0.19	2	-0.4	2	4
STK36	0.022	0.006	0.12	2	-10000	0	2
Gi family/GNB1/GNG2/GDP	-0.003	0.055	-10000	0	-0.42	2	2
PTCH1	0.032	0.079	0.35	1	-0.64	1	2
MIM/GLI1	0.039	0.079	0.32	2	-0.69	1	3
CREBBP	0.017	0.05	0.12	2	-0.27	19	21
Su(fu)/SIN3/HDAC complex	-0.009	0.09	0.16	1	-0.27	60	61

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	0.035	0.12	-10000	0	-0.53	25	25
oxygen homeostasis	0.004	0.003	-10000	0	-10000	0	0
TCEB2	0.021	0.002	-10000	0	-10000	0	0
TCEB1	0.02	0.004	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	0.037	0.053	0.18	2	-10000	0	2
EPO	0.048	0.067	0.26	16	-10000	0	16
FIH (dimer)	0.022	0.01	-10000	0	-10000	0	0
APEX1	0.026	0.01	-10000	0	-10000	0	0
SERPINE1	0.045	0.072	0.25	18	-0.31	3	21
FLT1	0.014	0.12	-10000	0	-0.52	23	23
ADORA2A	0.038	0.057	0.27	6	-10000	0	6
germ cell development	0.05	0.062	0.27	5	-10000	0	5
SLC11A2	0.049	0.062	0.27	5	-10000	0	5
BHLHE40	0.049	0.069	0.27	5	-0.32	6	11
HIF1AN	0.022	0.01	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	0.051	0.061	0.2	18	-10000	0	18
ETS1	0.028	0.02	0.13	22	-10000	0	22
CITED2	0.008	0.11	-10000	0	-0.5	25	25
KDR	0.032	0.065	-10000	0	-0.53	7	7
PGK1	0.05	0.063	0.27	5	-10000	0	5
SIRT1	0.019	0.006	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF2A/ARNT	0.1	0.091	0.31	27	-10000	0	27
EPAS1	0.021	0.022	0.11	1	-10000	0	1
SP1	0.031	0.015	-10000	0	-10000	0	0
ABCG2	0.051	0.062	0.28	5	-10000	0	5
EFNA1	0.049	0.061	0.23	3	-10000	0	3
FXN	0.038	0.056	0.27	6	-10000	0	6
POU5F1	0.051	0.063	0.27	5	-10000	0	5
neuron apoptosis	-0.099	0.089	-10000	0	-0.3	30	30
EP300	0.02	0.004	-10000	0	-10000	0	0
EGLN3	0.023	0.008	-10000	0	-10000	0	0
EGLN2	0.022	0.01	-10000	0	-10000	0	0
EGLN1	0.024	0.007	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.04	0.01	-10000	0	-10000	0	0
VHL	0.021	0.003	-10000	0	-10000	0	0
ARNT	0.026	0.009	-10000	0	-10000	0	0
SLC2A1	0.04	0.052	0.24	6	-10000	0	6
TWIST1	0.03	0.055	0.29	5	-0.29	2	7
ELK1	0.023	0.001	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.058	0.062	0.21	2	-10000	0	2
VEGFA	0.055	0.071	0.24	24	-10000	0	24
CREBBP	0.021	0.002	-10000	0	-10000	0	0

×

IGF1 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.021	0.001	-10000	0	-10000	0	0
PTK2	0.019	0.006	-10000	0	-10000	0	0
CRKL	-0.012	0.012	-10000	0	-0.13	6	6
GRB2/SOS1/SHC	0.042	0.014	-10000	0	-10000	0	0
HRAS	0.02	0.005	-10000	0	-10000	0	0
IRS1/Crk	0.016	0.018	-10000	0	-0.13	7	7
IGF-1R heterotetramer/IGF1/PTP1B	0.037	0.02	0.16	1	-0.12	6	7
AKT1	-0.015	0.033	0.14	22	-0.12	6	28
BAD	-0.018	0.031	0.13	22	-0.12	6	28
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.013	0.013	-10000	0	-0.13	7	7
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.022	0.019	0.2	2	-0.13	7	9
RAF1	-0.002	0.044	0.26	1	-0.42	4	5
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.045	0.024	-10000	0	-0.13	6	6
YWHAZ	0.02	0.005	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.025	0.018	-10000	0	-0.14	7	7
PIK3CA	0.021	0.003	-10000	0	-10000	0	0
RPS6KB1	-0.016	0.032	0.14	21	-0.12	5	26
GNB2L1	0.023	0.016	0.12	15	-10000	0	15
positive regulation of MAPKKK cascade	-0.008	0.042	0.23	2	-0.35	3	5
PXN	0.021	0.002	-10000	0	-10000	0	0
PIK3R1	0.021	0.003	-10000	0	-10000	0	0
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.03	0.006	-10000	0	-10000	0	0
HRAS/GTP	0.023	0.019	-10000	0	-0.12	6	6
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.057	0.027	-10000	0	-0.11	6	6
IGF-1R heterotetramer	0.021	0.009	-10000	0	-0.042	11	11
IGF-1R heterotetramer/IGF1/IRS/Nck	0.036	0.022	-10000	0	-0.13	7	7
Crk/p130 Cas/Paxillin	0.041	0.023	0.2	1	-0.13	7	8
IGF1R	0.021	0.009	-10000	0	-0.042	11	11
IGF1	0.022	0.008	0.16	1	-10000	0	1
IRS2/Crk	0.013	0.015	-10000	0	-0.13	7	7
PI3K	0.045	0.023	-10000	0	-0.13	6	6
apoptosis	0.017	0.034	-10000	0	-0.14	22	22
HRAS/GDP	0.015	0.003	-10000	0	-10000	0	0
PRKCD	0.003	0.032	-10000	0	-0.24	9	9
RAF1/14-3-3 E	0.012	0.046	0.25	1	-0.37	4	5
BAD/14-3-3	-0.017	0.035	0.15	22	-10000	0	22
PRKCZ	-0.013	0.029	0.13	18	-0.15	4	22
Crk/p130 Cas/Paxillin/FAK1	-0.026	0.024	0.12	10	-10000	0	10
PTPN1	0.02	0.004	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.008	0.036	-10000	0	-0.24	10	10
BCAR1	0.021	0.003	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.042	0.028	-10000	0	-0.12	5	5
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.021	0.001	-10000	0	-10000	0	0
IRS1/NCK2	0.022	0.021	0.12	8	-0.13	7	15
GRB10	0.017	0.008	-10000	0	-10000	0	0
PTPN11	-0.013	0.013	0.075	1	-0.13	7	8
IRS1	0.008	0.018	0.12	1	-0.14	7	8
IRS2	-0.012	0.014	0.075	1	-0.13	7	8
IGF-1R heterotetramer/IGF1	0.028	0.023	0.17	1	-0.18	7	8
GRB2	0.02	0.004	-10000	0	-10000	0	0
PDPK1	-0.014	0.031	0.17	14	-0.13	6	20
YWHAE	0.021	0.002	-10000	0	-10000	0	0
PRKD1	0.002	0.035	-10000	0	-0.23	11	11
SHC1	0.023	0.016	0.12	16	-10000	0	16

×

S1P3 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
PDGFRB	0.021	0.008	0.12	4	-10000	0	4
mol:S1P	0	0	-10000	0	-10000	0	0
S1P1/S1P/Gi	0.007	0.026	-10000	0	-0.19	8	8
GNAO1	0.021	0.004	-10000	0	-10000	0	0
S1P/S1P3/G12/G13	0.042	0.03	-10000	0	-10000	0	0
AKT1	0.012	0.071	-10000	0	-0.36	20	20
AKT3	0.02	0.056	-10000	0	-0.61	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.021	0.008	0.12	4	-10000	0	4
GNAI2	0.021	0.003	-10000	0	-10000	0	0
GNAI3	0.019	0.008	0.12	1	-10000	0	1
GNAI1	0.017	0.008	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
S1PR3	0.04	0.04	0.12	122	-10000	0	122
S1PR2	0.024	0.019	0.12	21	-10000	0	21
EDG1	0	0	-10000	0	-10000	0	0
mol:Ca2+	0.009	0.045	-10000	0	-0.21	4	4
MAPK3	0.011	0.048	-10000	0	-0.18	7	7
MAPK1	0.012	0.047	-10000	0	-0.2	4	4
JAK2	0.01	0.055	0.18	9	-0.24	9	18
CXCR4	0.014	0.049	-10000	0	-0.2	4	4
FLT1	0.021	0.005	-10000	0	-10000	0	0
RhoA/GDP	0.015	0.002	-10000	0	-10000	0	0
Rac1/GDP	0.013	0.006	-10000	0	-10000	0	0
SRC	0.009	0.046	-10000	0	-0.2	4	4
S1P/S1P3/Gi	0.009	0.046	-10000	0	-0.21	4	4
RAC1	0.018	0.008	-10000	0	-10000	0	0
RhoA/GTP	0.024	0.053	-10000	0	-0.31	2	2
VEGFA	0.034	0.034	0.12	79	-10000	0	79
S1P/S1P2/Gi	0.002	0.038	-10000	0	-0.18	9	9
VEGFR1 homodimer/VEGFA homodimer	0.039	0.025	-10000	0	-10000	0	0
RHOA	0.021	0.003	-10000	0	-10000	0	0
S1P/S1P3/Gq	0.02	0.017	-10000	0	-0.16	3	3
GNAQ	0.021	0.003	-10000	0	-10000	0	0
GNAZ	0.021	0.004	-10000	0	-10000	0	0
G12/G13	0.026	0.012	-10000	0	-10000	0	0
GNA14	0.021	0.003	-10000	0	-10000	0	0
GNA15	0.021	0.006	0.12	1	-10000	0	1
GNA12	0.018	0.008	-10000	0	-10000	0	0
GNA13	0.02	0.004	-10000	0	-10000	0	0
GNA11	0.02	0.004	-10000	0	-10000	0	0
Rac1/GTP	0.015	0.047	-10000	0	-0.31	2	2

×

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	0.032	0.065	-10000	0	-0.18	43	43
Ran/GTP/Exportin 1/HDAC1	-0.013	0.004	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.011	0.069	-10000	0	-0.21	44	44
SUMO1	0.021	0.001	-10000	0	-10000	0	0
ZFPM1	0.021	0.002	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.008	0.002	-10000	0	-10000	0	0
FKBP3	0.02	0.004	-10000	0	-10000	0	0
Histones	0.035	0.046	-10000	0	-0.16	3	3
YY1/LSF	0.016	0.036	-10000	0	-0.21	5	5
SMG5	0.021	0.003	-10000	0	-10000	0	0
RAN	0.021	0.002	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	0.005	0.042	-10000	0	-0.15	43	43
I kappa B alpha/HDAC1	0.015	0.045	-10000	0	-0.15	24	24
SAP18	0.02	0.005	-10000	0	-10000	0	0
RELA	0.008	0.046	0.13	3	-0.32	1	4
HDAC1/Smad7	0.03	0.02	-10000	0	-10000	0	0
RANGAP1	0.02	0.004	-10000	0	-10000	0	0
HDAC3/TR2	0.019	0.041	-10000	0	-0.15	7	7
NuRD/MBD3 Complex	0.009	0.03	-10000	0	-0.48	1	1
NF kappa B1 p50/RelA	0.015	0.058	0.17	3	-0.3	5	8
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	0.021	0.008	0.12	4	-10000	0	4
GATA1	0.02	0.008	0.12	3	-10000	0	3
Mad/Max	0.03	0.007	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	-0.002	0.053	-10000	0	-0.39	1	1
RBBP7	0.021	0.002	-10000	0	-10000	0	0
NPC	0.012	0.001	-10000	0	-10000	0	0
RBBP4	0.019	0.006	-10000	0	-10000	0	0
MAX	0.02	0.005	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.021	0.003	-10000	0	-10000	0	0
NFKBIA	0.006	0.031	-10000	0	-0.11	42	42
KAT2B	0.021	0.005	0.12	1	-10000	0	1
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.006	0.03	-10000	0	-10000	0	0
SIN3 complex	0.048	0.018	-10000	0	-10000	0	0
SMURF1	0.017	0.009	-10000	0	-10000	0	0
CHD3	0.021	0.003	-10000	0	-10000	0	0
SAP30	0.021	0.006	0.12	1	-10000	0	1
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.021	0.002	-10000	0	-10000	0	0
YY1/HDAC3	0.006	0.04	-10000	0	-0.18	9	9
YY1/HDAC2	0.017	0.033	-10000	0	-0.2	5	5
YY1/HDAC1	0.014	0.036	-10000	0	-0.22	5	5
NuRD/MBD2 Complex (MeCP1)	0.008	0.031	-10000	0	-0.29	3	3
PPARG	0.001	0.053	0.15	3	-0.19	44	47
HDAC8/hEST1B	0.04	0.01	-10000	0	-10000	0	0
UBE2I	0.021	0.002	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.021	0.003	-10000	0	-10000	0	0
TNFRSF1A	0.021	0.01	0.12	5	-10000	0	5
HDAC3/SMRT (N-CoR2)	0.018	0.041	-10000	0	-0.15	8	8
MBD3L2	0.015	0.003	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.03	0.019	-10000	0	-10000	0	0
CREBBP	0.021	0.002	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.006	0.052	-10000	0	-10000	0	0
HDAC1	0.019	0.006	-10000	0	-10000	0	0
HDAC3	0.006	0.032	-10000	0	-10000	0	0
HDAC2	0.02	0.004	-10000	0	-10000	0	0
YY1	0.01	0.004	-10000	0	-10000	0	0
HDAC8	0.021	0.002	-10000	0	-10000	0	0
SMAD7	0.021	0.003	-10000	0	-10000	0	0
NCOR2	0.021	0.002	-10000	0	-10000	0	0
MXD1	0.021	0.001	-10000	0	-10000	0	0
STAT3	0.013	0.003	-10000	0	-10000	0	0
NFKB1	0.021	0.002	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.021	0.001	-10000	0	-10000	0	0
YY1/LSF/HDAC1	0.024	0.037	-10000	0	-0.19	5	5
YY1/SAP30/HDAC1	0.024	0.037	-10000	0	-0.2	5	5
EP300	0.02	0.004	-10000	0	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.013	0.003	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.006	0.031	-10000	0	-0.11	42	42
histone deacetylation	0.008	0.031	-10000	0	-0.29	3	3
STAT3 (dimer non-phopshorylated)/HDAC3	0.009	0.034	-10000	0	-0.17	1	1
nuclear export	-0.04	0.01	-10000	0	-10000	0	0
PRKACA	0.02	0.004	-10000	0	-10000	0	0
GATAD2B	0.021	0.002	-10000	0	-10000	0	0
GATAD2A	0.02	0.004	-10000	0	-10000	0	0
GATA2/HDAC3	0.02	0.041	0.17	1	-0.15	7	8
GATA1/HDAC1	0.027	0.011	-10000	0	-10000	0	0
GATA1/HDAC3	0.016	0.04	-10000	0	-0.16	7	7
CHD4	0.02	0.005	-10000	0	-10000	0	0
TNF-alpha/TNFR1A	0.019	0.049	-10000	0	-0.16	44	44
SIN3/HDAC complex/Mad/Max	0.002	0.048	-10000	0	-0.26	11	11
NuRD Complex	0.006	0.056	-10000	0	-0.24	6	6
positive regulation of chromatin silencing	0.033	0.044	-10000	0	-0.16	3	3
SIN3B	0.02	0.004	-10000	0	-10000	0	0
MTA2	0.021	0.003	-10000	0	-10000	0	0
SIN3A	0.021	0.003	-10000	0	-10000	0	0
XPO1	0.021	0.001	-10000	0	-10000	0	0
SUMO1/HDAC1	0.025	0.025	-10000	0	-0.24	1	1
HDAC complex	0.046	0.02	-10000	0	-10000	0	0
GATA1/Fog1	0.03	0.007	-10000	0	-10000	0	0
FKBP25/HDAC1/HDAC2	0.036	0.016	-10000	0	-10000	0	0
TNF	0.021	0.015	0.12	11	-10000	0	11
negative regulation of cell growth	0.002	0.047	-10000	0	-0.26	11	11
NuRD/MBD2/PRMT5 Complex	0.008	0.031	-10000	0	-0.29	3	3
Ran/GTP/Exportin 1	0.029	0.023	-10000	0	-0.23	1	1
NF kappa B/RelA/I kappa B alpha	0.001	0.06	-10000	0	-0.22	42	42
SIN3/HDAC complex/NCoR1	-0.001	0.057	-10000	0	-0.26	7	7
TFCP2	0.021	0.003	-10000	0	-10000	0	0
NR2C1	0.021	0.002	-10000	0	-10000	0	0
MBD3	0.02	0.004	-10000	0	-10000	0	0
MBD2	0.021	0.003	-10000	0	-10000	0	0

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.009	0.003	-10000	0	-10000	0	0
ADCY5	-0.009	0.003	-10000	0	-10000	0	0
ADCY6	-0.009	0.002	-10000	0	-10000	0	0
ADCY7	-0.01	0.002	-10000	0	-10000	0	0
ADCY1	-0.006	0.005	-10000	0	-10000	0	0
ADCY2	-0.009	0.003	-10000	0	-10000	0	0
ADCY3	-0.01	0.002	-10000	0	-10000	0	0
ADCY8	-0.008	0.005	0.023	12	-10000	0	12
PRKCE	-0.006	0.001	-10000	0	-10000	0	0
ADCY9	-0.01	0.002	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	-0.007	0.065	0.17	24	-0.24	21	45

×

Regulation of cytoplasmic and nuclear SMAD2/3 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.021	0.003	-10000	0	-10000	0	0
SMAD2	-0.007	0.038	0.15	1	-0.17	17	18
SMAD3	0.014	0.026	0.12	12	-10000	0	12
SMAD3/SMAD4	0.022	0.048	-10000	0	-0.41	6	6
SMAD4/Ubc9/PIASy	0.04	0.01	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.031	0.048	-10000	0	-0.2	6	6
PPM1A	0.02	0.004	-10000	0	-10000	0	0
CALM1	0.02	0.005	-10000	0	-10000	0	0
SMAD2/SMAD4	0.004	0.041	-10000	0	-0.17	19	19
MAP3K1	0.024	0.018	0.12	21	-10000	0	21
TRAP-1/SMAD4	0.029	0.017	-10000	0	-0.16	5	5
MAPK3	0.021	0.002	-10000	0	-10000	0	0
MAPK1	0.021	0.003	-10000	0	-10000	0	0
NUP214	0.021	0.003	-10000	0	-10000	0	0
CTDSP1	0.021	0.004	0.12	1	-10000	0	1
CTDSP2	0.019	0.006	-10000	0	-10000	0	0
CTDSPL	0.021	0.002	-10000	0	-10000	0	0
KPNB1	0.021	0.002	-10000	0	-10000	0	0
TGFBRAP1	0.021	0.002	-10000	0	-10000	0	0
UBE2I	0.021	0.002	-10000	0	-10000	0	0
NUP153	0.021	0.003	-10000	0	-10000	0	0
KPNA2	0.021	0.003	-10000	0	-10000	0	0
PIAS4	0.02	0.004	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.046	0.021	-10000	0	-0.11	2	2
HDAC3	0.021	0.002	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.014	0.003	-10000	0	-10000	0	0
GATA1/HDAC4	0.029	0.007	-10000	0	-10000	0	0
GATA1/HDAC5	0.03	0.006	-10000	0	-10000	0	0
GATA2/HDAC5	0.031	0.007	0.11	4	-10000	0	4
HDAC5/BCL6/BCoR	0.041	0.008	-10000	0	-10000	0	0
HDAC9	0.018	0.008	-10000	0	-10000	0	0
Glucocorticoid receptor/Hsp90/HDAC6	0.04	0.01	-10000	0	-10000	0	0
HDAC4/ANKRA2	0.03	0.006	-10000	0	-10000	0	0
HDAC5/YWHAB	0.03	0.007	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.008	0.002	-10000	0	-10000	0	0
GATA2	0.021	0.008	0.12	4	-10000	0	4
HDAC4/RFXANK	0.03	0.01	-10000	0	-10000	0	0
BCOR	0.021	0.002	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.02	0.004	-10000	0	-10000	0	0
HDAC5	0.021	0.002	-10000	0	-10000	0	0
GNB1/GNG2	0.027	0.015	-10000	0	-0.16	2	2
Histones	0.021	0.035	-10000	0	-0.39	1	1
ADRBK1	0.021	0.003	-10000	0	-10000	0	0
HDAC4	0.021	0.003	-10000	0	-10000	0	0
XPO1	0.021	0.001	-10000	0	-10000	0	0
HDAC5/ANKRA2	0.031	0.004	-10000	0	-10000	0	0
HDAC4/Ubc9	0.03	0.006	-10000	0	-10000	0	0
HDAC7	0.02	0.004	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.031	0.004	-10000	0	-10000	0	0
TUBA1B	0.02	0.004	-10000	0	-10000	0	0
HDAC6	0.021	0.001	-10000	0	-10000	0	0
HDAC5/RFXANK	0.031	0.009	0.11	5	-10000	0	5
CAMK4	0.015	0.01	-10000	0	-10000	0	0
Tubulin/HDAC6	0.041	0.011	-10000	0	-0.13	1	1
SUMO1	0.021	0.001	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.02	0.004	-10000	0	-10000	0	0
GATA1	0.02	0.008	0.12	3	-10000	0	3
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.021	0.002	-10000	0	-10000	0	0
NR3C1	0.021	0.002	-10000	0	-10000	0	0
SUMO1/HDAC4	0.028	0.024	-10000	0	-0.23	1	1
SRF	0.021	0.002	-10000	0	-10000	0	0
HDAC4/YWHAB	0.029	0.008	-10000	0	-10000	0	0
Tubulin	0.03	0.01	-10000	0	-0.16	1	1
HDAC4/14-3-3 E	0.03	0.006	-10000	0	-10000	0	0
GNB1	0.019	0.007	-10000	0	-10000	0	0
RANGAP1	0.02	0.004	-10000	0	-10000	0	0
BCL6/BCoR	0.03	0.006	-10000	0	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0.041	0.009	-10000	0	-10000	0	0
HDAC4/SRF	-0.006	0.077	-10000	0	-0.13	180	180
HDAC4/ER alpha	0.029	0.011	-10000	0	-0.16	1	1
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.021	0.035	-10000	0	-0.39	1	1
cell motility	0.04	0.011	-10000	0	-0.13	1	1
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.021	0.002	-10000	0	-10000	0	0
HDAC7/HDAC3	0.03	0.006	-10000	0	-10000	0	0
BCL6	0.021	0.003	-10000	0	-10000	0	0
HDAC4/CaMK II delta B	0.02	0.003	-10000	0	-10000	0	0
Hsp90/HDAC6	0.03	0.007	-10000	0	-10000	0	0
ESR1	0.02	0.005	-10000	0	-10000	0	0
HDAC6/HDAC11	0.031	0.004	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.029	0.023	-10000	0	-0.23	1	1
NPC	0.012	0.001	-10000	0	-10000	0	0
MEF2C	0.02	0.004	-10000	0	-10000	0	0
RAN	0.021	0.002	-10000	0	-10000	0	0
HDAC4/MEF2C	0.056	0.029	-10000	0	-0.12	13	13
GNG2	0.02	0.004	-10000	0	-10000	0	0
NCOR2	0.021	0.002	-10000	0	-10000	0	0
TUBB2A	0.021	0.003	-10000	0	-10000	0	0
HDAC11	0.021	0.002	-10000	0	-10000	0	0
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
RANBP2	0.021	0.001	-10000	0	-10000	0	0
ANKRA2	0.021	0.002	-10000	0	-10000	0	0
RFXANK	0.021	0.01	0.12	5	-10000	0	5
nuclear import	-0.024	0.007	-10000	0	-10000	0	0

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.006	0.025	0.14	24	-10000	0	24
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.001	0.028	0.12	3	-0.15	4	7
AP2	0.027	0.011	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.02	0.017	-10000	0	-10000	0	0
CLTB	0.021	0.002	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.01	0.006	-10000	0	-10000	0	0
CD4	0.022	0.014	0.12	11	-10000	0	11
CLTA	0.02	0.004	-10000	0	-10000	0	0
mol:GTP	-0.003	0.002	-10000	0	-10000	0	0
ARFGAP1	-0.006	0.001	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0.008	-10000	0	-10000	0	0
ARF1/GTP	0.023	0.011	-10000	0	-0.068	2	2
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.003	0.008	-10000	0	-10000	0	0
mol:Choline	0	0.008	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.018	0.012	-10000	0	-0.019	62	62
DDEF1	0	0.013	-10000	0	-10000	0	0
ARF1/GDP	0.001	0.016	-10000	0	-0.086	19	19
AP2M1	0.021	0.003	-10000	0	-10000	0	0
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	-0.008	0.006	-10000	0	-10000	0	0
Rac/GTP	0.011	0.009	-10000	0	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.023	0.016	-10000	0	-10000	0	0
ARFIP2	0.019	0.008	-10000	0	-0.035	3	3
COPA	0.021	0.002	-10000	0	-10000	0	0
RAC1	0.018	0.008	-10000	0	-10000	0	0
ARF1/GTP/coatomer protein complex	0.004	0.025	-10000	0	-0.14	14	14
ARF1/GTP/ARHGAP10	0.012	0.009	-10000	0	-10000	0	0
GGA3	0.02	0.004	-10000	0	-10000	0	0
ARF1/GTP/Membrin	0.015	0.016	-10000	0	-0.17	1	1
AP2A1	0.019	0.007	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.007	0.015	-10000	0	-0.18	4	4
ARF1/GDP/Membrin	0.017	0.016	-10000	0	-0.22	1	1
Arfaptin 2/Rac/GDP	0.023	0.012	-10000	0	-10000	0	0
CYTH2	0.019	0.007	-10000	0	-10000	0	0
ARF1/GTP/GGA3	0.023	0.015	-10000	0	-10000	0	0
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.013	0.006	-10000	0	-10000	0	0
mol:Brefeldin A	0	0	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.002	0.037	-10000	0	-0.18	10	10
PLD2	0	0.008	-10000	0	-10000	0	0
ARF-GAP1/v-SNARE	-0.006	0.001	-10000	0	-10000	0	0
PIP5K1A	0	0.009	-10000	0	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0.007	0.024	-10000	0	-0.13	2	2
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0	0.008	-10000	0	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	-0.006	0.001	-10000	0	-10000	0	0
GOSR2	0.008	0.007	-10000	0	-10000	0	0
USO1	0.004	0.035	-10000	0	-0.33	7	7
GBF1	-0.015	0.082	-10000	0	-0.31	46	46
ARF1/GTP/Arfaptin 2	0.024	0.017	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.036	0.019	-10000	0	-10000	0	0

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.044	0.045	-10000	0	-10000	0	0
CLOCK	0.021	0.006	-10000	0	-10000	0	0
TIMELESS/CRY2	0.029	0.037	-10000	0	-10000	0	0
DEC1/BMAL1	0.027	0.006	-10000	0	-10000	0	0
ATR	0.021	0.003	-10000	0	-10000	0	0
NR1D1	0.015	0.022	-10000	0	-10000	0	0
ARNTL	0.022	0.005	-10000	0	-10000	0	0
TIMELESS	0.02	0.033	-10000	0	-10000	0	0
NPAS2	0.023	0.003	-10000	0	-10000	0	0
CRY2	0.02	0.004	-10000	0	-10000	0	0
mol:CO	-0.007	0.01	-10000	0	-10000	0	0
CHEK1	0.029	0.028	0.12	52	-10000	0	52
mol:HEME	0.007	0.01	-10000	0	-10000	0	0
PER1	0.021	0.002	-10000	0	-10000	0	0
BMAL/CLOCK/NPAS2	0.044	0.029	-10000	0	-0.13	12	12
BMAL1/CLOCK	0.018	0.05	-10000	0	-10000	0	0
S phase of mitotic cell cycle	0.044	0.045	-10000	0	-10000	0	0
TIMELESS/CHEK1/ATR	0.044	0.046	-10000	0	-10000	0	0
mol:NADPH	0.007	0.01	-10000	0	-10000	0	0
PER1/TIMELESS	0.03	0.038	-10000	0	-10000	0	0
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.015	0.002	-10000	0	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

Figure S128. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S128. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	-0.014	0.004	-10000	0	-10000	0	0
SNTA1	0.02	0.005	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	-0.013	0.005	0.02	1	-10000	0	1
MAPK12	-0.007	0.002	-10000	0	-10000	0	0
CCND1	0.008	0.014	0.16	1	-10000	0	1
p38 gamma/SNTA1	-0.003	0.035	0.18	19	-10000	0	19
MAP2K3	0.021	0.004	0.12	1	-10000	0	1
PKN1	0.02	0.004	-10000	0	-10000	0	0
G2/M transition checkpoint	-0.007	0.002	-10000	0	-10000	0	0
MAP2K6	-0.004	0.001	-10000	0	-10000	0	0
MAPT	-0.002	0.039	0.16	8	-0.22	5	13
MAPK13	-0.012	0.004	0.051	1	-10000	0	1
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.004	0.001	-10000	0	-10000	0	0

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	-0.021	0.005	-10000	0	-0.12	1	1
PI3K Class IB/PDE3B	0.021	0.005	0.12	1	-10000	0	1
PDE3B	0.021	0.005	0.12	1	-10000	0	1

×

Sumoylation by RanBP2 regulates transcriptional repression

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
HDAC1	0.019	0.006	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.014	0.006	-9999	-10000	0	0
MDM2/SUMO1	0.028	0.023	-9999	-0.24	1	1
HDAC4	0.021	0.003	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	-0.013	0.007	-9999	-10000	0	0
SUMO1	0.021	0.001	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.007	0.011	-9999	-0.27	1	1
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0	0.015	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.021	0.002	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.021	0.001	-9999	-10000	0	0
SUMO1/HDAC4	0.028	0.024	-9999	-0.23	1	1
SUMO1/HDAC1	0.025	0.025	-9999	-0.24	1	1
RANGAP1	0.02	0.004	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	0.05	0.015	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.008	0.002	-9999	-10000	0	0
Ran/GTP	0.018	0.022	-9999	-0.25	1	1
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.02	0.004	-9999	-10000	0	0
UBE2I	0.021	0.002	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.014	0.021	-9999	-0.23	1	1
NPC	0.012	0.001	-9999	-10000	0	0
PIAS2	0.021	0.003	-9999	-10000	0	0
PIAS1	0.021	0.003	-9999	-10000	0	0
EntrezGene:9972	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
IKK alpha homodimer	0.028	0.01	-9999	-9999
FBXW11	0.021	0.003	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-9999
beta TrCP1/SCF ubiquitin ligase complex	0.021	0.003	-9999	-9999
CHUK	0.019	0.006	-9999	-9999
NF kappa B2 p100/RelB	0.05	0.025	-9999	-9999
NFKB1	0.021	0.002	-9999	-9999
MAP3K14	0.021	0.002	-9999	-9999
NF kappa B1 p50/RelB	0.027	0.01	-9999	-9999
RELB	0.019	0.007	-9999	-9999
NFKB2	0.019	0.006	-9999	-9999
NF kappa B2 p52/RelB	0.023	0.011	-9999	-9999
regulation of B cell activation	0.023	0.011	-9999	-9999

pid_entity	TCGA.WY.A85E	TCGA.WY.A85D	TCGA.WY.A85C	TCGA.WY.A85B
109_MAP3K5	0.014	-0.16	-0.13	-0.16
47_PPARGC1A	0.021	0.021	0.021	0.021
105_BMP4	0.021	0.021	0.021	0.021
105_BMP6	0.021	0.021	0.021	0.021
105_BMP7	0.021	0.021	0.021	0.021
105_BMP2	0.12	0.12	0.12	0.12
131_RELN/VLDLR	0.054	0.054	0.054	0.054
30_TGFB1/TGF beta receptor Type II	0.021	0.021	0.02	0.021
84_STAT5B	0.019	0.019	0.055	0.026
84_STAT5A	0.019	0.019	0.055	0.026