PARADIGM pathway analysis of mRNASeq expression data - Bladder Urothelial Carcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
FOXM1 transcription factor network	130
Glypican 2 network	103
Aurora B signaling	94
Signaling events regulated by Ret tyrosine kinase	72
Signaling mediated by p38-alpha and p38-beta	72
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	72
Nongenotropic Androgen signaling	61
Signaling events mediated by the Hedgehog family	60
IL4-mediated signaling events	59
Endothelins	56

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
FOXM1 transcription factor network	0.3641	130	6663	51	-0.86	0.016	1000	-1000	-0.13	-1000
Glypican 2 network	0.2885	103	412	4	-0.17	-0.13	1000	-1000	-0.011	-1000
Aurora B signaling	0.2633	94	6364	67	-0.51	0.016	1000	-1000	-0.057	-1000
Signaling events regulated by Ret tyrosine kinase	0.2017	72	5937	82	-0.32	0.016	1000	-1000	-0.073	-1000
Signaling mediated by p38-alpha and p38-beta	0.2017	72	3176	44	-0.26	0.016	1000	-1000	-0.049	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.2017	72	4945	68	-0.72	0.36	1000	-1000	-0.096	-1000
Nongenotropic Androgen signaling	0.1709	61	3196	52	-0.25	0.14	1000	-1000	-0.055	-1000
Signaling events mediated by the Hedgehog family	0.1681	60	3150	52	-0.18	0.18	1000	-1000	-0.047	-1000
IL4-mediated signaling events	0.1653	59	5374	91	-0.78	0.56	1000	-1000	-0.1	-1000
Endothelins	0.1569	56	5377	96	-0.33	0.042	1000	-1000	-0.059	-1000
IGF1 pathway	0.1541	55	3158	57	-0.25	0.047	1000	-1000	-0.079	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.1457	52	4092	78	-0.26	0.093	1000	-1000	-0.048	-1000
Reelin signaling pathway	0.1401	50	2801	56	-0.24	0.04	1000	-1000	-0.078	-1000
TCGA08_p53	0.1401	50	354	7	-0.17	0.078	1000	-1000	-0.011	-1000
Thromboxane A2 receptor signaling	0.1373	49	5169	105	-0.2	0.037	1000	-1000	-0.057	-1000
Aurora C signaling	0.1345	48	342	7	-0.22	0	1000	-1000	-0.024	-1000
TCGA08_retinoblastoma	0.1345	48	390	8	-0.25	0.068	1000	-1000	-0.012	-1000
Fc-epsilon receptor I signaling in mast cells	0.1289	46	4556	97	-0.2	0.042	1000	-1000	-0.072	-1000
p75(NTR)-mediated signaling	0.1261	45	5663	125	-0.17	0.046	1000	-1000	-0.085	-1000
PLK1 signaling events	0.1204	43	3735	85	-0.37	0.051	1000	-1000	-0.037	-1000
IL23-mediated signaling events	0.1204	43	2620	60	-0.62	0.016	1000	-1000	-0.11	-1000
Ephrin A reverse signaling	0.1176	42	295	7	-0.072	0	1000	-1000	-0.018	-1000
HIF-1-alpha transcription factor network	0.1176	42	3226	76	-0.36	0.033	1000	-1000	-0.064	-1000
Plasma membrane estrogen receptor signaling	0.1176	42	3636	86	-0.25	0.12	1000	-1000	-0.067	-1000
Ras signaling in the CD4+ TCR pathway	0.1176	42	721	17	-0.16	0.022	1000	-1000	-0.023	-1000
Integrins in angiogenesis	0.1148	41	3493	84	-0.28	0.032	1000	-1000	-0.076	-1000
Rapid glucocorticoid signaling	0.1148	41	837	20	-0.24	0.037	1000	-1000	-0.01	-1000
BMP receptor signaling	0.1120	40	3244	81	-0.33	0.053	1000	-1000	-0.082	-1000
Glypican 1 network	0.1064	38	1849	48	-0.26	0.036	1000	-1000	-0.025	-1000
amb2 Integrin signaling	0.1064	38	3149	82	-0.34	0.021	1000	-1000	-0.068	-1000
Calcium signaling in the CD4+ TCR pathway	0.1064	38	1181	31	-0.3	0.016	1000	-1000	-0.072	-1000
IL6-mediated signaling events	0.1064	38	2862	75	-0.25	0.07	1000	-1000	-0.063	-1000
Syndecan-1-mediated signaling events	0.1036	37	1287	34	-0.28	0.016	1000	-1000	-0.033	-1000
TCR signaling in naïve CD8+ T cells	0.1036	37	3519	93	-0.15	0.063	1000	-1000	-0.067	-1000
LPA receptor mediated events	0.1008	36	3674	102	-0.23	0.032	1000	-1000	-0.065	-1000
Glucocorticoid receptor regulatory network	0.0980	35	4038	114	-0.6	0.27	1000	-1000	-0.069	-1000
PDGFR-alpha signaling pathway	0.0952	34	1516	44	-0.34	0.033	1000	-1000	-0.053	-1000
S1P1 pathway	0.0952	34	1253	36	-0.32	0.016	1000	-1000	-0.047	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0924	33	3997	120	-0.33	0.18	1000	-1000	-0.07	-1000
S1P5 pathway	0.0868	31	541	17	-0.17	0.11	1000	-1000	-0.027	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0868	31	1655	52	-0.32	0.028	1000	-1000	-0.048	-1000
IL12-mediated signaling events	0.0812	29	2574	87	-0.42	0.035	1000	-1000	-0.093	-1000
Visual signal transduction: Cones	0.0812	29	1130	38	-0.13	0.017	1000	-1000	-0.056	-1000
LPA4-mediated signaling events	0.0784	28	345	12	-0.17	0.023	1000	-1000	-0.015	-1000
Osteopontin-mediated events	0.0784	28	1095	38	-0.19	0.017	1000	-1000	-0.084	-1000
BCR signaling pathway	0.0784	28	2814	99	-0.19	0.037	1000	-1000	-0.076	-1000
S1P4 pathway	0.0784	28	703	25	-0.17	0.031	1000	-1000	-0.034	-1000
JNK signaling in the CD4+ TCR pathway	0.0756	27	459	17	-0.16	0.019	1000	-1000	-0.026	-1000
Coregulation of Androgen receptor activity	0.0728	26	2013	76	-0.24	0.033	1000	-1000	-0.042	-1000
Syndecan-2-mediated signaling events	0.0728	26	1835	69	-0.087	0.031	1000	-1000	-0.026	-1000
S1P3 pathway	0.0728	26	1112	42	-0.17	0.032	1000	-1000	-0.027	-1000
Aurora A signaling	0.0700	25	1554	60	-0.36	0.031	1000	-1000	-0.043	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0700	25	2287	88	-0.23	0.048	1000	-1000	-0.091	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0672	24	1338	54	-0.2	0.031	1000	-1000	-0.086	-1000
Arf6 signaling events	0.0672	24	1510	62	-0.24	0.03	1000	-1000	-0.042	-1000
Class IB PI3K non-lipid kinase events	0.0672	24	72	3	-0.024	-1000	1000	-1000	-0.008	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0616	22	755	34	-0.052	0.016	1000	-1000	-0.051	-1000
Syndecan-4-mediated signaling events	0.0616	22	1498	67	-0.19	0.02	1000	-1000	-0.067	-1000
FAS signaling pathway (CD95)	0.0588	21	1010	47	-0.57	0.019	1000	-1000	-0.026	-1000
Wnt signaling	0.0588	21	153	7	-0.058	0.016	1000	-1000	-0.022	-1000
Presenilin action in Notch and Wnt signaling	0.0560	20	1262	61	-0.18	0.044	1000	-1000	-0.053	-1000
Visual signal transduction: Rods	0.0560	20	1047	52	-0.21	0.016	1000	-1000	-0.073	-1000
Canonical Wnt signaling pathway	0.0532	19	1007	51	-0.18	0.083	1000	-1000	-0.039	-1000
Noncanonical Wnt signaling pathway	0.0504	18	487	26	-0.1	0.016	1000	-1000	-0.044	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0476	17	500	28	-0.17	0.03	1000	-1000	-0.022	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0476	17	564	33	-0.29	0.046	1000	-1000	-0.047	-1000
ErbB2/ErbB3 signaling events	0.0448	16	1075	65	-0.24	0.027	1000	-1000	-0.06	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0448	16	1397	85	-0.22	0.023	1000	-1000	-0.063	-1000
Effects of Botulinum toxin	0.0448	16	416	26	-0.072	0.016	1000	-1000	-0.056	-1000
Caspase cascade in apoptosis	0.0420	15	1155	74	-0.058	0.043	1000	-1000	-0.029	-1000
ErbB4 signaling events	0.0420	15	1089	69	-0.24	0.038	1000	-1000	-0.07	-1000
FOXA2 and FOXA3 transcription factor networks	0.0420	15	725	46	-0.19	0.095	1000	-1000	-0.037	-1000
Regulation of Androgen receptor activity	0.0392	14	988	70	-0.22	0.03	1000	-1000	-0.048	-1000
Hedgehog signaling events mediated by Gli proteins	0.0364	13	863	65	-0.17	0.067	1000	-1000	-0.047	-1000
Nectin adhesion pathway	0.0364	13	881	63	-0.054	0.03	1000	-1000	-0.061	-1000
IL27-mediated signaling events	0.0364	13	713	51	-0.25	0.029	1000	-1000	-0.066	-1000
EGFR-dependent Endothelin signaling events	0.0364	13	293	21	-0.071	0.023	1000	-1000	-0.062	-1000
IL2 signaling events mediated by STAT5	0.0336	12	284	22	-0.12	0.068	1000	-1000	-0.036	-1000
Regulation of nuclear SMAD2/3 signaling	0.0308	11	1527	136	-0.2	0.069	1000	-1000	-0.063	-1000
Cellular roles of Anthrax toxin	0.0308	11	464	39	-0.1	0.018	1000	-1000	-0.019	-1000
IL2 signaling events mediated by PI3K	0.0308	11	653	58	-0.21	0.055	1000	-1000	-0.066	-1000
Signaling events mediated by PTP1B	0.0280	10	815	76	-0.14	0.036	1000	-1000	-0.065	-1000
Syndecan-3-mediated signaling events	0.0280	10	364	35	-0.13	0.046	1000	-1000	-0.035	-1000
Signaling events mediated by HDAC Class III	0.0252	9	383	40	-0.23	0.026	1000	-1000	-0.031	-1000
IL1-mediated signaling events	0.0252	9	615	62	-0.094	0.075	1000	-1000	-0.081	-1000
Ephrin B reverse signaling	0.0252	9	468	48	-0.057	0.018	1000	-1000	-0.059	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0252	9	788	83	-0.28	0.043	1000	-1000	-0.056	-1000
Regulation of p38-alpha and p38-beta	0.0252	9	510	54	-0.15	0.043	1000	-1000	-0.05	-1000
BARD1 signaling events	0.0224	8	468	57	-0.16	0.045	1000	-1000	-0.048	-1000
a4b1 and a4b7 Integrin signaling	0.0224	8	44	5	-0.004	0.009	1000	-1000	-0.015	-1000
Class I PI3K signaling events mediated by Akt	0.0224	8	569	68	-0.21	0.061	1000	-1000	-0.044	-1000
EPHB forward signaling	0.0224	8	697	85	-0.047	0.041	1000	-1000	-0.078	-1000
Regulation of Telomerase	0.0224	8	886	102	-0.17	0.038	1000	-1000	-0.099	-1000
Signaling events mediated by PRL	0.0224	8	273	34	-0.1	0.026	1000	-1000	-0.028	-1000
E-cadherin signaling events	0.0224	8	42	5	-0.006	0.016	1000	-1000	-0.016	-1000
EPO signaling pathway	0.0196	7	403	55	-0.047	0.057	1000	-1000	-0.073	-1000
IFN-gamma pathway	0.0196	7	487	68	-0.18	0.056	1000	-1000	-0.079	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0196	7	280	37	-0.031	0.035	1000	-1000	-0.044	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0196	7	570	74	-0.25	0.077	1000	-1000	-0.077	-1000
Arf6 trafficking events	0.0196	7	533	71	-0.42	0.05	1000	-1000	-0.061	-1000
Insulin Pathway	0.0196	7	570	74	-0.26	0.042	1000	-1000	-0.082	-1000
PDGFR-beta signaling pathway	0.0196	7	754	97	-0.056	0.054	1000	-1000	-0.075	-1000
TRAIL signaling pathway	0.0168	6	316	48	-0.011	0.051	1000	-1000	-0.057	-1000
Ceramide signaling pathway	0.0140	5	384	76	-0.25	0.044	1000	-1000	-0.028	-1000
Signaling mediated by p38-gamma and p38-delta	0.0140	5	89	15	0	0.032	1000	-1000	-0.021	-1000
Retinoic acid receptors-mediated signaling	0.0140	5	315	58	-0.08	0.036	1000	-1000	-0.062	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0140	5	247	45	-0.032	0.068	1000	-1000	-0.077	-1000
TCGA08_rtk_signaling	0.0140	5	134	26	-0.069	0.048	1000	-1000	-0.014	-1000
PLK2 and PLK4 events	0.0112	4	14	3	0.005	0.019	1000	-1000	-0.009	-1000
E-cadherin signaling in the nascent adherens junction	0.0112	4	369	76	-0.02	0.058	1000	-1000	-0.07	-1000
Signaling events mediated by HDAC Class II	0.0084	3	269	75	-0.086	0.039	1000	-1000	-0.037	-1000
HIF-2-alpha transcription factor network	0.0084	3	147	43	-0.16	0.16	1000	-1000	-0.061	-1000
Paxillin-dependent events mediated by a4b1	0.0084	3	123	36	-0.035	0.036	1000	-1000	-0.056	-1000
Class I PI3K signaling events	0.0084	3	253	73	-0.054	0.041	1000	-1000	-0.057	-1000
E-cadherin signaling in keratinocytes	0.0084	3	129	43	-0.046	0.048	1000	-1000	-0.056	-1000
p38 MAPK signaling pathway	0.0084	3	160	44	-0.044	0.047	1000	-1000	-0.054	-1000
Canonical NF-kappaB pathway	0.0056	2	91	39	-0.021	0.092	1000	-1000	-0.069	-1000
ceramide signaling pathway	0.0056	2	99	49	-0.024	0.051	1000	-1000	-0.033	-1000
FoxO family signaling	0.0056	2	160	64	-0.067	0.098	1000	-1000	-0.048	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0056	2	310	125	-0.054	0.099	1000	-1000	-0.082	-1000
Circadian rhythm pathway	0.0028	1	36	22	-0.016	0.053	1000	-1000	-0.039	-1000
Insulin-mediated glucose transport	0.0028	1	60	32	-0.14	0.042	1000	-1000	-0.046	-1000
mTOR signaling pathway	0.0028	1	63	53	-0.006	0.042	1000	-1000	-0.056	-1000
VEGFR1 specific signals	0.0028	1	89	56	-0.051	0.071	1000	-1000	-0.041	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	12	23	0.007	0.055	1000	-1000	-0.045	-1000
Arf6 downstream pathway	0.0000	0	20	43	-0.039	0.039	1000	-1000	-0.03	-1000
Signaling events mediated by HDAC Class I	0.0000	0	81	104	-0.031	0.066	1000	-1000	-0.059	-1000
Atypical NF-kappaB pathway	0.0000	0	23	31	0	0.056	1000	-1000	-0.026	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	24	27	-0.002	0.039	1000	-1000	-0.045	-1000
Arf1 pathway	0.0000	0	6	54	0	0.04	1000	-1000	-0.028	-1000
Alternative NF-kappaB pathway	0.0000	0	0	13	0	0.046	1000	-1000	-0.026	-1000
Total	NA	3095	179636	7203	-25	-990	131000	-131000	-6.8	-131000

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.65	0.52	-9999	-1.1	177	177
PLK1	-0.13	0.18	-9999	-10000	0	0
BIRC5	-0.25	0.19	-9999	-1.5	1	1
HSPA1B	-0.65	0.52	-9999	-1.1	174	174
MAP2K1	-0.007	0.031	-9999	-10000	0	0
BRCA2	-0.66	0.53	-9999	-1.1	180	180
FOXM1	-0.86	0.73	-9999	-1.4	198	198
XRCC1	-0.65	0.52	-9999	-1.1	182	182
FOXM1B/p19	-0.76	0.51	-9999	-1.1	217	217
Cyclin D1/CDK4	-0.59	0.47	-9999	-0.98	178	178
CDC2	-0.7	0.55	-9999	-1.1	198	198
TGFA	-0.56	0.45	-9999	-0.93	177	177
SKP2	-0.65	0.52	-9999	-1.1	179	179
CCNE1	-0.073	0.19	-9999	-0.52	56	56
CKS1B	-0.65	0.52	-9999	-1.1	182	182
RB1	-0.25	0.15	-9999	-0.46	13	13
FOXM1C/SP1	-0.76	0.62	-9999	-1.2	195	195
AURKB	-0.16	0.19	-9999	-10000	0	0
CENPF	-0.73	0.56	-9999	-1.2	192	192
CDK4	0.004	0.03	-9999	-0.51	1	1
MYC	-0.57	0.46	-9999	-0.94	184	184
CHEK2	-0.007	0.031	-9999	-10000	0	0
ONECUT1	-0.63	0.5	-9999	-1	185	185
CDKN2A	-0.24	0.26	-9999	-0.5	174	174
LAMA4	-0.66	0.53	-9999	-1.1	182	182
FOXM1B/HNF6	-0.75	0.62	-9999	-1.2	185	185
FOS	-0.77	0.61	-9999	-1.2	197	197
SP1	0.016	0.001	-9999	-10000	0	0
CDC25B	-0.65	0.52	-9999	-1.1	180	180
response to radiation	-0.023	0.03	-9999	-10000	0	0
CENPB	-0.65	0.52	-9999	-1.1	182	182
CENPA	-0.74	0.56	-9999	-1.2	196	196
NEK2	-0.73	0.56	-9999	-1.2	193	193
HIST1H2BA	-0.66	0.52	-9999	-1.1	182	182
CCNA2	-0.13	0.23	-9999	-0.52	94	94
EP300	0.016	0	-9999	-10000	0	0
CCNB1/CDK1	-0.78	0.64	-9999	-1.3	184	184
CCNB2	-0.74	0.56	-9999	-1.2	197	197
CCNB1	-0.72	0.57	-9999	-1.2	186	186
ETV5	-0.65	0.52	-9999	-1.1	176	176
ESR1	-0.73	0.57	-9999	-1.2	194	194
CCND1	-0.61	0.49	-9999	-1	178	178
GSK3A	0.003	0.025	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	-0.12	0.2	-9999	-0.37	128	128
CDK2	0.01	0.007	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.03	0.035	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.75	0.51	-9999	-1.1	200	200
GAS1	-0.78	0.56	-9999	-1.1	220	220
MMP2	-0.67	0.55	-9999	-1.1	184	184
RB1/FOXM1C	-0.64	0.52	-9999	-1.1	182	182
CREBBP	0.016	0	-9999	-10000	0	0

×

Glypican 2 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.014	0.12	-9999	-0.51	20	20
GPC2	-0.17	0.25	-9999	-0.51	124	124
GPC2/Midkine	-0.13	0.2	-9999	-0.38	134	134
neuron projection morphogenesis	-0.13	0.2	-9999	-0.38	134	134

×

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.15	0.15	-9999	-0.32	113	113
STMN1	-0.17	0.22	-9999	-0.39	171	171
Aurora B/RasGAP/Survivin	-0.32	0.24	-9999	-0.45	263	263
Chromosomal passenger complex/Cul3 protein complex	-0.18	0.16	-9999	-0.36	127	127
BIRC5	-0.37	0.24	-9999	-0.51	259	259
DES	-0.51	0.37	-9999	-0.77	233	233
Aurora C/Aurora B/INCENP	-0.11	0.15	-9999	-0.27	169	169
Aurora B/TACC1	-0.12	0.16	-9999	-0.3	162	162
Aurora B/PP2A	-0.14	0.19	-9999	-0.35	161	161
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.021	0.045	-9999	-10000	0	0
mitotic metaphase/anaphase transition	-0.003	0.004	-9999	-10000	0	0
NDC80	-0.25	0.29	-9999	-0.51	184	184
Cul3 protein complex	-0.063	0.17	-9999	-0.36	86	86
KIF2C	-0.12	0.099	-9999	-0.2	202	202
PEBP1	0.006	0.007	-9999	-10000	0	0
KIF20A	-0.38	0.23	-9999	-0.51	266	266
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.14	0.19	-9999	-0.35	161	161
SEPT1	0.011	0.048	-9999	-0.51	3	3
SMC2	0.014	0.028	-9999	-0.51	1	1
SMC4	0.016	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.058	0.068	-9999	-10000	0	0
PSMA3	0.016	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.002	0.004	-9999	-10000	0	0
H3F3B	-0.068	0.099	-9999	-0.18	161	161
AURKB	-0.22	0.27	-9999	-0.51	161	161
AURKC	-0.001	0.09	-9999	-0.51	11	11
CDCA8	-0.13	0.23	-9999	-0.52	95	95
cytokinesis	-0.26	0.18	-9999	-0.41	191	191
Aurora B/Septin1	-0.24	0.19	-9999	-0.42	145	145
AURKA	-0.14	0.24	-9999	-0.51	104	104
INCENP	0.005	0.029	-9999	-0.53	1	1
KLHL13	-0.11	0.24	-9999	-0.58	76	76
BUB1	-0.081	0.2	-9999	-0.51	65	65
hSgo1/Aurora B/Survivin	-0.41	0.3	-9999	-0.53	280	280
EVI5	0.014	0.002	-9999	-10000	0	0
RhoA/GTP	-0.27	0.21	-9999	-0.46	180	180
SGOL1	-0.21	0.26	-9999	-0.51	152	152
CENPA	-0.18	0.14	-9999	-0.3	172	172
NCAPG	-0.21	0.26	-9999	-0.51	155	155
Aurora B/HC8 Proteasome	-0.14	0.19	-9999	-0.35	161	161
NCAPD2	0.014	0.028	-9999	-0.51	1	1
Aurora B/PP1-gamma	-0.14	0.19	-9999	-0.35	161	161
RHOA	0.016	0	-9999	-10000	0	0
NCAPH	-0.31	0.25	-9999	-0.51	221	221
NPM1	-0.066	0.083	-9999	-10000	0	0
RASA1	0.016	0	-9999	-10000	0	0
KLHL9	-0.009	0.12	-9999	-0.58	15	15
mitotic prometaphase	-0.009	0.007	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.14	0.19	-9999	-0.35	161	161
PPP1CC	0.016	0	-9999	-10000	0	0
Centraspindlin	-0.3	0.23	-9999	-0.48	193	193
RhoA/GDP	0.012	0	-9999	-10000	0	0
NSUN2	-0.066	0.083	-9999	-10000	0	0
MYLK	-0.19	0.2	-9999	-0.31	228	228
KIF23	-0.25	0.26	-9999	-0.51	178	178
VIM	-0.15	0.2	-9999	-0.36	165	165
RACGAP1	0.008	0.04	-9999	-0.52	2	2
mitosis	0	0	-9999	-10000	0	0
NCL	-0.066	0.083	-9999	-10000	0	0
Chromosomal passenger complex	-0.2	0.16	-9999	-0.33	189	189
Chromosomal passenger complex/EVI5	-0.32	0.29	-9999	-0.57	177	177
TACC1	0.012	0.044	-9999	-0.58	2	2
PPP2R5D	0.016	0	-9999	-10000	0	0
CUL3	0.016	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.048	0.044	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.15	0.13	-9999	-0.4	26	26
JUN	-0.11	0.15	-9999	-0.44	21	21
HRAS	0.016	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.18	0.19	-9999	-0.33	201	201
RAP1A	0.016	0	-9999	-10000	0	0
FRS2	0.005	0.072	-9999	-0.51	7	7
RAP1A/GDP	0.012	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.17	0.19	-9999	-0.33	200	200
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.17	0.17	-9999	-0.32	199	199
RHOA	0.016	0	-9999	-10000	0	0
RAP1A/GTP	-0.16	0.15	-9999	-0.55	13	13
GRB7	-0.013	0.12	-9999	-0.52	19	19
RET51/GFRalpha1/GDNF	-0.17	0.19	-9999	-0.33	200	200
MAPKKK cascade	-0.15	0.14	-9999	-0.5	13	13
BCAR1	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.18	0.18	-9999	-0.33	201	201
lamellipodium assembly	-0.15	0.13	-9999	-0.38	26	26
RET51/GFRalpha1/GDNF/SHC	-0.17	0.19	-9999	-0.33	200	200
PIK3CA	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.17	0.18	-9999	-0.32	199	199
RET9/GFRalpha1/GDNF/Shank3	-0.17	0.17	-9999	-0.32	199	199
MAPK3	-0.13	0.16	-9999	-0.51	13	13
DOK1	0.014	0.028	-9999	-0.51	1	1
DOK6	-0.2	0.28	-9999	-0.58	130	130
PXN	0.016	0	-9999	-10000	0	0
neurite development	-0.16	0.18	-9999	-0.38	98	98
DOK5	-0.043	0.18	-9999	-0.57	35	35
GFRA1	-0.32	0.29	-9999	-0.58	199	199
MAPK8	-0.12	0.14	-9999	-0.42	16	16
HRAS/GTP	-0.18	0.16	-9999	-0.58	13	13
tube development	-0.15	0.16	-9999	-0.3	199	199
MAPK1	-0.13	0.16	-9999	-0.51	13	13
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.13	0.14	-9999	-0.26	199	199
Rac1/GDP	0.012	0	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
PDLIM7	0.016	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.27	0.25	-9999	-0.61	99	99
SHC1	0.014	0.028	-9999	-0.51	1	1
RET51/GFRalpha1/GDNF/Dok4	-0.17	0.19	-9999	-0.33	200	200
RET51/GFRalpha1/GDNF/Dok5	-0.2	0.22	-9999	-0.36	210	210
PRKCA	0.011	0.054	-9999	-0.58	3	3
HRAS/GDP	0.012	0	-9999	-10000	0	0
CREB1	-0.15	0.17	-9999	-0.29	199	199
PIK3R1	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.13	0.14	-9999	-0.25	199	199
RET51/GFRalpha1/GDNF/Grb7	-0.19	0.2	-9999	-0.35	202	202
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.011	0.12	-9999	-0.55	17	17
DOK4	0.016	0	-9999	-10000	0	0
JNK cascade	-0.11	0.15	-9999	-0.43	21	21
RET9/GFRalpha1/GDNF/FRS2	-0.17	0.18	-9999	-0.32	203	203
SHANK3	0.016	0	-9999	-10000	0	0
RASA1	0.016	0	-9999	-10000	0	0
NCK1	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.13	0.14	-9999	-0.26	199	199
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.13	0.15	-9999	-0.45	17	17
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.13	0.15	-9999	-0.27	122	122
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.14	0.17	-9999	-0.58	14	14
PI3K	-0.19	0.23	-9999	-0.38	199	199
SOS1	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.15	0.16	-9999	-0.3	199	199
GRB10	0.009	0.062	-9999	-0.58	4	4
activation of MAPKK activity	-0.12	0.14	-9999	-0.4	16	16
RET51/GFRalpha1/GDNF/FRS2	-0.18	0.19	-9999	-0.33	201	201
GAB1	0.016	0	-9999	-10000	0	0
IRS1	0.004	0.082	-9999	-0.58	7	7
IRS2	-0.008	0.12	-9999	-0.58	14	14
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.14	0.17	-9999	-0.28	122	122
RET51/GFRalpha1/GDNF/PKC alpha	-0.18	0.19	-9999	-0.33	200	200
GRB2	0.016	0	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
GDNF	0.003	0.048	-9999	-0.51	3	3
RAC1	0.016	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.18	0.19	-9999	-0.34	202	202
Rac1/GTP	-0.17	0.15	-9999	-0.46	26	26
RET9/GFRalpha1/GDNF	-0.2	0.19	-9999	-0.36	199	199
GFRalpha1/GDNF	-0.23	0.22	-9999	-0.42	199	199

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.26	0.51	-9999	-1.1	90	90
MKNK1	0.016	0	-9999	-10000	0	0
MAPK14	-0.061	0.15	-9999	-0.29	95	95
ATF2/c-Jun	-0.05	0.2	-9999	-0.81	15	15
MAPK11	-0.061	0.15	-9999	-0.29	95	95
MITF	-0.093	0.22	-9999	-0.39	111	111
MAPKAPK5	-0.063	0.18	-9999	-0.35	95	95
KRT8	-0.075	0.21	-9999	-0.38	98	98
MAPKAPK3	0.016	0	-9999	-10000	0	0
MAPKAPK2	0.016	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.092	0.22	-9999	-0.44	95	95
CEBPB	-0.064	0.18	-9999	-0.36	95	95
SLC9A1	-0.062	0.18	-9999	-0.35	95	95
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.058	0.18	-9999	-0.35	95	95
p38alpha-beta/MNK1	-0.06	0.18	-9999	-0.34	95	95
JUN	-0.049	0.19	-9999	-0.8	15	15
PPARGC1A	-0.22	0.28	-9999	-0.42	206	206
USF1	-0.063	0.18	-9999	-0.35	95	95
RAB5/GDP/GDI1	-0.07	0.11	-9999	-0.35	17	17
NOS2	-0.094	0.25	-9999	-0.77	22	22
DDIT3	-0.063	0.18	-9999	-0.35	95	95
RAB5A	0.016	0	-9999	-10000	0	0
HSPB1	-0.042	0.15	-9999	-0.4	17	17
p38alpha-beta/HBP1	-0.06	0.18	-9999	-0.34	95	95
CREB1	-0.068	0.2	-9999	-0.38	95	95
RAB5/GDP	0.012	0	-9999	-10000	0	0
EIF4E	-0.046	0.16	-9999	-0.43	17	17
RPS6KA4	-0.062	0.18	-9999	-0.35	95	95
PLA2G4A	-0.066	0.19	-9999	-0.5	35	35
GDI1	-0.062	0.18	-9999	-0.35	95	95
TP53	-0.083	0.22	-9999	-0.43	95	95
RPS6KA5	-0.074	0.2	-9999	-0.38	99	99
ESR1	-0.13	0.25	-9999	-0.41	137	137
HBP1	0.016	0	-9999	-10000	0	0
MEF2C	-0.075	0.2	-9999	-0.36	103	103
MEF2A	-0.062	0.18	-9999	-0.35	95	95
EIF4EBP1	-0.069	0.2	-9999	-0.38	96	96
KRT19	-0.081	0.21	-9999	-0.39	102	102
ELK4	-0.062	0.18	-9999	-0.35	95	95
ATF6	-0.062	0.18	-9999	-0.35	95	95
ATF1	-0.068	0.2	-9999	-0.38	96	96
p38alpha-beta/MAPKAPK2	-0.06	0.18	-9999	-0.34	95	95
p38alpha-beta/MAPKAPK3	-0.06	0.18	-9999	-0.34	95	95

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	0.003	0.1	-10000	0	-0.63	8	8
NFATC2	-0.11	0.28	-10000	0	-0.64	63	63
NFATC3	-0.092	0.13	-10000	0	-0.31	36	36
CD40LG	-0.55	0.54	-10000	0	-1.1	165	165
ITCH	0.029	0.084	-10000	0	-0.41	1	1
CBLB	0.029	0.081	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.38	0.45	-10000	0	-1.1	77	77
JUNB	0.009	0.062	-10000	0	-0.58	4	4
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.027	0.081	-10000	0	-0.28	32	32
T cell anergy	-0.007	0.13	-10000	0	-0.39	32	32
TLE4	-0.069	0.24	-10000	0	-0.63	40	40
Jun/NFAT1-c-4/p21SNFT	-0.46	0.56	-10000	0	-1	152	152
AP-1/NFAT1-c-4	-0.64	0.7	-10000	0	-1.3	165	165
IKZF1	-0.067	0.24	-10000	0	-0.64	36	36
T-helper 2 cell differentiation	-0.24	0.35	-10000	0	-0.91	60	60
AP-1/NFAT1	-0.2	0.27	-10000	0	-0.51	125	125
CALM1	0.016	0.053	-10000	0	-10000	0	0
EGR2	-0.51	0.74	-10000	0	-1.5	108	108
EGR3	-0.72	0.84	-10000	0	-1.6	171	171
NFAT1/FOXP3	-0.081	0.22	-10000	0	-0.51	58	58
EGR1	-0.13	0.25	-10000	0	-0.58	87	87
JUN	-0.012	0.11	-10000	0	-0.58	13	13
EGR4	-0.011	0.12	-10000	0	-0.55	16	16
mol:Ca2+	-0.001	0.057	-10000	0	-10000	0	0
GBP3	-0.059	0.22	-10000	0	-0.56	37	37
FOSL1	-0.024	0.15	-10000	0	-0.58	24	24
NFAT1-c-4/MAF/IRF4	-0.45	0.56	-10000	0	-0.95	173	173
DGKA	-0.054	0.21	-10000	0	-0.54	34	34
CREM	0.015	0.001	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.48	0.55	-10000	0	-0.97	173	173
CTLA4	-0.069	0.23	-10000	0	-0.7	29	29
NFAT1-c-4 (dimer)/EGR1	-0.51	0.62	-10000	0	-1.1	174	174
NFAT1-c-4 (dimer)/EGR4	-0.46	0.56	-10000	0	-0.96	175	175
FOS	-0.18	0.28	-10000	0	-0.59	110	110
IFNG	-0.25	0.3	-10000	0	-0.78	66	66
T cell activation	-0.26	0.32	-10000	0	-0.76	63	63
MAF	-0.001	0.098	-10000	0	-0.58	10	10
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.36	0.5	0.79	171	-10000	0	171
TNF	-0.44	0.52	-10000	0	-0.94	163	163
FASLG	-0.69	0.81	-10000	0	-1.4	180	180
TBX21	-0.024	0.14	-10000	0	-0.57	21	21
BATF3	0.003	0.084	-10000	0	-0.55	8	8
PRKCQ	-0.042	0.18	-10000	0	-0.57	35	35
PTPN1	-0.054	0.21	-10000	0	-0.55	32	32
NFAT1-c-4/ICER1	-0.46	0.54	-10000	0	-0.96	173	173
GATA3	-0.025	0.15	-10000	0	-0.57	25	25
T-helper 1 cell differentiation	-0.23	0.31	-10000	0	-0.75	68	68
IL2RA	-0.38	0.43	-10000	0	-1	82	82
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.054	0.21	-10000	0	-0.55	33	33
E2F1	-0.095	0.22	-10000	0	-0.5	81	81
PPARG	-0.024	0.15	-10000	0	-0.57	24	24
SLC3A2	-0.055	0.21	-10000	0	-0.53	40	40
IRF4	-0.035	0.16	-10000	0	-0.57	31	31
PTGS2	-0.58	0.57	-10000	0	-1.1	172	172
CSF2	-0.56	0.52	-10000	0	-1	175	175
JunB/Fra1/NFAT1-c-4	-0.44	0.55	-10000	0	-0.94	173	173
IL4	-0.25	0.38	-10000	0	-0.99	58	58
IL5	-0.53	0.52	-10000	0	-1	163	163
IL2	-0.26	0.32	-10000	0	-0.77	63	63
IL3	-0.082	0.062	-10000	0	-10000	0	0
RNF128	-0.01	0.2	-10000	0	-0.63	34	34
NFATC1	-0.36	0.51	-10000	0	-0.8	171	171
CDK4	0.18	0.27	0.64	37	-10000	0	37
PTPRK	-0.054	0.21	-10000	0	-0.5	48	48
IL8	-0.55	0.55	-10000	0	-1.1	167	167
POU2F1	0.016	0.002	-10000	0	-10000	0	0

×

Nongenotropic Androgen signaling

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
PTK2	0.013	0.001	-10000	0	-10000	0	0
GNB1/GNG2	-0.1	0.17	-10000	0	-0.32	132	132
regulation of S phase of mitotic cell cycle	-0.068	0.14	-10000	0	-0.25	128	128
GNAO1	-0.17	0.27	-10000	0	-0.58	110	110
HRAS	0.015	0.002	-10000	0	-10000	0	0
SHBG/T-DHT	0.01	0.002	-10000	0	-10000	0	0
PELP1	0.015	0.002	-10000	0	-10000	0	0
AKT1	0.013	0.001	-10000	0	-10000	0	0
MAP2K1	-0.085	0.15	-10000	0	-0.35	48	48
T-DHT/AR	-0.15	0.21	-10000	0	-0.43	128	128
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.002	0.003	-10000	0	-0.006	110	110
GNAI2	0.015	0	-10000	0	-10000	0	0
GNAI3	0.015	0	-10000	0	-10000	0	0
GNAI1	0.01	0.054	-10000	0	-0.58	3	3
mol:GDP	-0.16	0.21	-10000	0	-0.44	128	128
cell proliferation	-0.16	0.24	-10000	0	-0.45	111	111
PIK3CA	0.016	0	-10000	0	-10000	0	0
FOS	-0.25	0.4	-10000	0	-0.84	110	110
mol:Ca2+	-0.045	0.044	-10000	0	-0.085	166	166
MAPK3	-0.13	0.19	-10000	0	-0.49	48	48
MAPK1	-0.069	0.12	-10000	0	-0.27	47	47
PIK3R1	0.016	0	-10000	0	-10000	0	0
mol:IP3	-0.001	0.002	-10000	0	-0.004	110	110
cAMP biosynthetic process	0.039	0.037	-10000	0	-10000	0	0
GNG2	0.006	0.076	-10000	0	-0.58	6	6
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.004	110	110
HRAS/GTP	-0.11	0.14	-10000	0	-0.29	128	128
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0.015	0.002	-10000	0	-10000	0	0
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.004	110	110
PI3K	0.021	0	-10000	0	-10000	0	0
apoptosis	0.14	0.23	0.45	110	-10000	0	110
T-DHT/AR/PELP1	-0.12	0.18	-10000	0	-0.36	128	128
HRAS/GDP	-0.15	0.2	-10000	0	-0.42	128	128
CREB1	-0.15	0.24	-10000	0	-0.49	110	110
RAC1-CDC42/GTP	0	0	-10000	0	-10000	0	0
AR	-0.2	0.28	-10000	0	-0.58	128	128
GNB1	0.016	0	-10000	0	-10000	0	0
RAF1	-0.088	0.15	-10000	0	-0.34	48	48
RAC1-CDC42/GDP	-0.14	0.19	-10000	0	-0.39	128	128
T-DHT/AR/PELP1/Src	-0.099	0.17	-10000	0	-0.32	128	128
MAP2K2	-0.085	0.15	-10000	0	-0.35	48	48
T-DHT/AR/PELP1/Src/PI3K	-0.069	0.14	-10000	0	-0.25	128	128
GNAZ	-0.11	0.24	-10000	0	-0.58	76	76
SHBG	0.015	0.003	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.16	0.25	-10000	0	-0.46	125	125
mol:T-DHT	0	0.001	-10000	0	-0.003	62	62
RAC1	0.016	0	-10000	0	-10000	0	0
GNRH1	0.013	0.001	-10000	0	-10000	0	0
Gi family/GTP	-0.16	0.21	-10000	0	-0.41	116	116
CDC42	0.016	0	-10000	0	-10000	0	0

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.055	0.24	-10000	0	-0.63	41	41
IHH	-0.061	0.19	-10000	0	-0.52	48	48
SHH Np/Cholesterol/GAS1	-0.17	0.2	-10000	0	-0.35	189	189
LRPAP1	0.014	0.028	-10000	0	-0.51	1	1
dorsoventral neural tube patterning	0.17	0.2	0.35	189	-10000	0	189
SMO/beta Arrestin2	-0.046	0.16	-10000	0	-0.5	22	22
SMO	-0.057	0.17	-10000	0	-0.49	29	29
AKT1	-0.002	0.08	-10000	0	-0.29	3	3
ARRB2	0.016	0	-10000	0	-10000	0	0
BOC	-0.037	0.17	-10000	0	-0.58	32	32
ADRBK1	0.016	0	-10000	0	-10000	0	0
heart looping	-0.056	0.17	-10000	0	-0.48	29	29
STIL	-0.15	0.21	-10000	0	-0.48	73	73
DHH N/PTCH2	-0.017	0.13	-10000	0	-0.43	31	31
DHH N/PTCH1	-0.036	0.16	-10000	0	-0.5	22	22
PIK3CA	0.016	0	-10000	0	-10000	0	0
DHH	-0.016	0.13	-10000	0	-0.58	18	18
PTHLH	-0.1	0.36	-10000	0	-1	41	41
determination of left/right symmetry	-0.056	0.17	-10000	0	-0.48	29	29
PIK3R1	0.016	0	-10000	0	-10000	0	0
skeletal system development	-0.1	0.36	-10000	0	-1	41	41
IHH N/Hhip	-0.14	0.23	-10000	0	-0.48	104	104
DHH N/Hhip	-0.11	0.21	-10000	0	-0.43	106	106
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.056	0.17	-10000	0	-0.48	29	29
pancreas development	-0.14	0.26	-10000	0	-0.57	92	92
HHAT	0.016	0	-10000	0	-10000	0	0
PI3K	0.023	0	-10000	0	-10000	0	0
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.12	0.25	-10000	0	-0.57	83	83
somite specification	-0.056	0.17	-10000	0	-0.48	29	29
SHH Np/Cholesterol/PTCH1	-0.12	0.19	-10000	0	-0.45	53	53
SHH Np/Cholesterol/PTCH2	-0.11	0.17	-10000	0	-0.32	137	137
SHH Np/Cholesterol/Megalin	-0.16	0.2	-10000	0	-0.35	169	169
SHH	-0.14	0.21	-10000	0	-0.41	128	128
catabolic process	-0.03	0.16	-10000	0	-0.54	15	15
SMO/Vitamin D3	-0.11	0.2	-10000	0	-0.47	47	47
SHH Np/Cholesterol/Hhip	-0.18	0.22	-10000	0	-0.38	182	182
LRP2	-0.093	0.21	-10000	0	-0.51	73	73
receptor-mediated endocytosis	-0.15	0.21	-10000	0	-0.48	63	63
SHH Np/Cholesterol/BOC	-0.13	0.18	-10000	0	-0.33	150	150
SHH Np/Cholesterol/CDO	-0.14	0.19	-10000	0	-0.33	167	167
mesenchymal cell differentiation	0.18	0.22	0.38	182	-10000	0	182
mol:Vitamin D3	-0.12	0.19	-10000	0	-0.45	53	53
IHH N/PTCH2	-0.04	0.14	-10000	0	-0.33	62	62
CDON	-0.067	0.2	-10000	0	-0.58	50	50
IHH N/PTCH1	-0.03	0.16	-10000	0	-0.54	15	15
Megalin/LRPAP1	-0.057	0.15	-10000	0	-0.36	74	74
PTCH2	-0.008	0.12	-10000	0	-0.58	14	14
SHH Np/Cholesterol	-0.11	0.16	-10000	0	-0.32	128	128
PTCH1	-0.03	0.16	-10000	0	-0.54	15	15
HHIP	-0.14	0.26	-10000	0	-0.57	92	92

×

IL4-mediated signaling events

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
BCL2L1	-0.48	0.56	-10000	0	-1.2	109	109
STAT6 (cleaved dimer)	-0.56	0.55	-10000	0	-1.1	140	140
IGHG1	-0.15	0.2	-10000	0	-0.37	71	71
IGHG3	-0.48	0.54	-10000	0	-1.1	123	123
AKT1	-0.21	0.31	-10000	0	-0.77	43	43
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.17	0.29	-10000	0	-0.76	35	35
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.23	0.32	-10000	0	-0.74	48	48
THY1	-0.49	0.56	-10000	0	-1.2	109	109
MYB	-0.051	0.17	-10000	0	-0.51	45	45
HMGA1	0.007	0.067	-10000	0	-0.51	6	6
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.31	0.4	-10000	0	-0.77	104	104
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.23	0.32	-10000	0	-0.71	56	56
SP1	0.023	0.009	-10000	0	-10000	0	0
INPP5D	0.004	0.082	-10000	0	-0.58	7	7
SOCS5	0.029	0.018	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.51	0.56	-10000	0	-1.2	120	120
SOCS1	-0.29	0.36	-10000	0	-0.75	89	89
SOCS3	-0.31	0.46	-10000	0	-1.3	52	52
FCER2	-0.72	0.73	-10000	0	-1.4	174	174
PARP14	0.01	0.014	-10000	0	-10000	0	0
CCL17	-0.51	0.56	-10000	0	-1.2	107	107
GRB2	0.016	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.17	0.25	-10000	0	-0.63	33	33
T cell proliferation	-0.49	0.59	-10000	0	-1.2	116	116
IL4R/JAK1	-0.49	0.56	-10000	0	-1.2	113	113
EGR2	-0.67	0.72	-10000	0	-1.4	144	144
JAK2	-0.006	0.046	-10000	0	-0.61	1	1
JAK3	0.015	0.041	-10000	0	-0.52	2	2
PIK3R1	0.016	0	-10000	0	-10000	0	0
JAK1	0.009	0.016	-10000	0	-10000	0	0
COL1A2	-0.2	0.39	-10000	0	-1.6	22	22
CCL26	-0.5	0.57	-10000	0	-1.2	109	109
IL4R	-0.52	0.61	-10000	0	-1.3	112	112
PTPN6	0.025	0.031	-10000	0	-0.5	1	1
IL13RA2	-0.52	0.59	-10000	0	-1.2	115	115
IL13RA1	-0.006	0.046	-10000	0	-0.62	1	1
IRF4	-0.25	0.49	-10000	0	-1.3	56	56
ARG1	-0.12	0.2	-10000	0	-0.67	19	19
CBL	-0.28	0.37	-10000	0	-0.74	93	93
GTF3A	0.024	0.005	-10000	0	-10000	0	0
PIK3CA	0.016	0	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.009	0.059	-10000	0	-0.46	2	2
IRF4/BCL6	-0.2	0.45	-10000	0	-1.2	53	53
CD40LG	-0.053	0.19	-10000	0	-0.58	40	40
MAPK14	-0.3	0.42	-10000	0	-0.84	87	87
mitosis	-0.2	0.29	-10000	0	-0.72	43	43
STAT6	-0.58	0.71	-10000	0	-1.4	122	122
SPI1	0	0.099	-10000	0	-0.55	11	11
RPS6KB1	-0.19	0.28	-10000	0	-0.7	40	40
STAT6 (dimer)	-0.58	0.71	-10000	0	-1.4	122	122
STAT6 (dimer)/PARP14	-0.57	0.63	-10000	0	-1.2	139	139
mast cell activation	0.011	0.014	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.22	0.34	-10000	0	-0.79	49	49
FRAP1	-0.21	0.31	-10000	0	-0.77	43	43
LTA	-0.5	0.59	-10000	0	-1.2	113	113
FES	0.014	0.031	-10000	0	-0.58	1	1
T-helper 1 cell differentiation	0.56	0.66	1.3	122	-10000	0	122
CCL11	-0.51	0.6	-10000	0	-1.2	115	115
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.22	0.32	-10000	0	-0.78	44	44
IL2RG	-0.009	0.12	-10000	0	-0.55	17	17
IL10	-0.51	0.6	-10000	0	-1.3	110	110
IRS1	0.004	0.082	-10000	0	-0.58	7	7
IRS2	-0.008	0.12	-10000	0	-0.58	14	14
IL4	-0.1	0.14	-10000	0	-10000	0	0
IL5	-0.49	0.56	-10000	0	-1.2	106	106
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.38	0.43	-10000	0	-0.88	112	112
COL1A1	-0.17	0.32	-10000	0	-1.7	10	10
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.5	0.58	-10000	0	-1.2	106	106
IL2R gamma/JAK3	-0.002	0.099	-10000	0	-0.43	17	17
TFF3	-0.65	0.7	-10000	0	-1.4	143	143
ALOX15	-0.53	0.57	-10000	0	-1.2	124	124
MYBL1	0.01	0.055	-10000	0	-0.51	4	4
T-helper 2 cell differentiation	-0.41	0.47	-10000	0	-0.96	118	118
SHC1	0.014	0.028	-10000	0	-0.51	1	1
CEBPB	0.015	0.034	-10000	0	-0.58	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.22	0.32	-10000	0	-0.71	52	52
mol:PI-3-4-5-P3	-0.21	0.31	-10000	0	-0.77	43	43
PI3K	-0.23	0.34	-10000	0	-0.84	43	43
DOK2	-0.007	0.11	-10000	0	-0.57	14	14
ETS1	0.027	0.014	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.16	0.24	-10000	0	-0.63	27	27
ITGB3	-0.55	0.65	-10000	0	-1.3	117	117
PIGR	-0.78	0.73	-10000	0	-1.4	182	182
IGHE	0.033	0.049	-10000	0	-0.23	1	1
MAPKKK cascade	-0.15	0.23	-10000	0	-0.62	27	27
BCL6	0.02	0.01	-10000	0	-10000	0	0
OPRM1	-0.49	0.56	-10000	0	-1.2	109	109
RETNLB	-0.5	0.56	-10000	0	-1.2	109	109
SELP	-0.62	0.7	-10000	0	-1.4	131	131
AICDA	-0.48	0.54	-10000	0	-1.2	108	108

×

Endothelins

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
AKT1	-0.008	0.24	-10000	0	-0.58	35	35
PTK2B	0.014	0.031	-10000	0	-0.58	1	1
mol:Ca2+	-0.012	0.22	-10000	0	-0.67	23	23
EDN1	0.042	0.11	-10000	0	-0.45	8	8
EDN3	-0.002	0.061	-10000	0	-0.51	5	5
EDN2	-0.053	0.18	-10000	0	-0.54	44	44
HRAS/GDP	-0.069	0.24	-10000	0	-0.49	62	62
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.026	0.19	-10000	0	-0.43	43	43
ADCY4	-0.15	0.26	-10000	0	-0.59	62	62
ADCY5	-0.3	0.34	-10000	0	-0.65	142	142
ADCY6	-0.15	0.26	-10000	0	-0.6	60	60
ADCY7	-0.15	0.26	-10000	0	-0.6	60	60
ADCY1	-0.15	0.27	-10000	0	-0.61	63	63
ADCY2	-0.26	0.32	-10000	0	-0.65	114	114
ADCY3	-0.15	0.26	-10000	0	-0.6	60	60
ADCY8	-0.16	0.26	-10000	0	-0.61	60	60
ADCY9	-0.15	0.27	-10000	0	-0.61	61	61
arachidonic acid secretion	-0.12	0.28	-10000	0	-0.53	89	89
ETB receptor/Endothelin-1/Gq/GTP	-0.04	0.19	-10000	0	-0.48	40	40
GNAO1	-0.17	0.27	-10000	0	-0.58	110	110
HRAS	0.013	0.006	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	0.041	0.26	0.26	126	-0.54	35	161
ETA receptor/Endothelin-1/Gs/GTP	-0.12	0.32	0.24	86	-0.62	64	150
mol:GTP	-0.001	0.006	-10000	0	-10000	0	0
COL3A1	-0.017	0.27	-10000	0	-0.82	24	24
EDNRB	-0.053	0.19	-10000	0	-0.57	42	42
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.013	0.24	-10000	0	-0.64	27	27
CYSLTR1	-0.03	0.28	-10000	0	-0.72	38	38
SLC9A1	-0.002	0.13	-10000	0	-0.34	21	21
mol:GDP	-0.083	0.25	-10000	0	-0.53	63	63
SLC9A3	-0.028	0.24	-10000	0	-0.62	37	37
RAF1	-0.13	0.28	-10000	0	-0.53	86	86
JUN	-0.032	0.29	-10000	0	-0.89	27	27
JAK2	-0.009	0.24	-10000	0	-0.59	35	35
mol:IP3	-0.048	0.21	-10000	0	-0.51	44	44
ETA receptor/Endothelin-1	0.031	0.31	0.29	130	-0.63	40	170
PLCB1	-0.004	0.098	-10000	0	-0.58	10	10
PLCB2	0.009	0.045	-10000	0	-0.58	2	2
ETA receptor/Endothelin-3	-0.038	0.2	-10000	0	-0.47	57	57
FOS	-0.28	0.48	-10000	0	-0.95	115	115
Gai/GDP	-0.25	0.41	-10000	0	-0.84	110	110
CRK	0.016	0.001	-10000	0	-10000	0	0
mol:Ca ++	-0.074	0.29	-10000	0	-0.61	59	59
BCAR1	0.016	0.001	-10000	0	-10000	0	0
PRKCB1	-0.049	0.2	-10000	0	-0.48	48	48
GNAQ	0.014	0.009	-10000	0	-10000	0	0
GNAZ	-0.11	0.24	-10000	0	-0.58	76	76
GNAL	-0.24	0.29	-10000	0	-0.58	154	154
Gs family/GDP	-0.22	0.25	-10000	0	-0.52	124	124
ETA receptor/Endothelin-1/Gq/GTP	-0.029	0.21	-10000	0	-0.49	42	42
MAPK14	-0.025	0.17	-10000	0	-0.51	26	26
TRPC6	-0.015	0.24	-10000	0	-0.72	23	23
GNAI2	0.016	0	-10000	0	-10000	0	0
GNAI3	0.016	0	-10000	0	-10000	0	0
GNAI1	0.011	0.054	-10000	0	-0.58	3	3
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.034	0.18	-10000	0	-0.48	35	35
ETB receptor/Endothelin-2	-0.076	0.19	-10000	0	-0.43	79	79
ETB receptor/Endothelin-3	-0.041	0.15	-10000	0	-0.41	47	47
ETB receptor/Endothelin-1	-0.011	0.17	-10000	0	-0.41	45	45
MAPK3	-0.23	0.42	-10000	0	-0.79	119	119
MAPK1	-0.23	0.42	-10000	0	-0.79	119	119
Rac1/GDP	-0.068	0.24	-10000	0	-0.49	61	61
cAMP biosynthetic process	-0.24	0.29	-10000	0	-0.53	153	153
MAPK8	-0.028	0.25	-10000	0	-0.68	33	33
SRC	0.016	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.11	0.22	-10000	0	-0.43	82	82
p130Cas/CRK/Src/PYK2	-0.061	0.24	-10000	0	-0.55	50	50
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.068	0.24	-10000	0	-0.49	62	62
COL1A2	-0.058	0.35	-10000	0	-0.98	35	35
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.08	0.22	-10000	0	-0.43	94	94
mol:DAG	-0.048	0.21	-10000	0	-0.51	44	44
MAP2K2	-0.17	0.33	-10000	0	-0.59	120	120
MAP2K1	-0.17	0.33	-10000	0	-0.59	120	120
EDNRA	-0.037	0.26	-10000	0	-0.64	53	53
positive regulation of muscle contraction	0.001	0.21	-10000	0	-0.59	25	25
Gq family/GDP	-0.13	0.2	-10000	0	-0.51	62	62
HRAS/GTP	-0.098	0.24	-10000	0	-0.51	67	67
PRKCH	-0.041	0.2	-10000	0	-0.5	42	42
RAC1	0.016	0	-10000	0	-10000	0	0
PRKCA	-0.043	0.2	-10000	0	-0.5	43	43
PRKCB	-0.13	0.26	-10000	0	-0.5	96	96
PRKCE	-0.04	0.2	-10000	0	-0.49	42	42
PRKCD	-0.042	0.2	-10000	0	-0.49	44	44
PRKCG	-0.055	0.2	-10000	0	-0.5	43	43
regulation of vascular smooth muscle contraction	-0.33	0.56	-10000	0	-1.1	115	115
PRKCQ	-0.071	0.23	-10000	0	-0.51	59	59
PLA2G4A	-0.14	0.31	-10000	0	-0.58	89	89
GNA14	-0.069	0.21	-10000	0	-0.58	50	50
GNA15	0.012	0.044	-10000	0	-0.58	2	2
GNA12	0.016	0	-10000	0	-10000	0	0
GNA11	0.013	0.032	-10000	0	-0.58	1	1
Rac1/GTP	0.041	0.26	0.26	122	-0.57	31	153
MMP1	-0.19	0.23	0.33	2	-0.4	175	177

×

IGF1 pathway

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
NCK2	0.016	0	-10000	0	-10000	0	0
PTK2	0.016	0	-10000	0	-10000	0	0
CRKL	-0.12	0.16	-10000	0	-0.29	162	162
GRB2/SOS1/SHC	0.031	0.017	-10000	0	-0.29	1	1
HRAS	0.016	0	-10000	0	-10000	0	0
IRS1/Crk	-0.11	0.16	-10000	0	-0.29	160	160
IGF-1R heterotetramer/IGF1/PTP1B	-0.15	0.16	-10000	0	-0.33	160	160
AKT1	-0.074	0.14	-10000	0	-0.46	6	6
BAD	-0.062	0.13	-10000	0	-0.42	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.11	0.16	-10000	0	-0.29	160	160
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.11	0.16	-10000	0	-0.29	160	160
RAF1	-0.054	0.13	-10000	0	-0.4	6	6
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.099	0.16	-10000	0	-0.52	6	6
YWHAZ	0.016	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.13	0.18	-10000	0	-0.32	163	163
PIK3CA	0.016	0	-10000	0	-10000	0	0
RPS6KB1	-0.074	0.14	-10000	0	-0.46	6	6
GNB2L1	0.016	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.05	0.12	-10000	0	-0.34	6	6
PXN	0.016	0	-10000	0	-10000	0	0
PIK3R1	0.016	0	-10000	0	-10000	0	0
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.023	0	-10000	0	-10000	0	0
HRAS/GTP	-0.1	0.12	-10000	0	-0.46	7	7
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.085	0.15	-10000	0	-0.4	7	7
IGF-1R heterotetramer	-0.023	0.068	-10000	0	-0.63	3	3
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.11	0.16	-10000	0	-0.29	160	160
Crk/p130 Cas/Paxillin	-0.087	0.15	-10000	0	-0.5	6	6
IGF1R	-0.023	0.068	-10000	0	-0.64	3	3
IGF1	-0.25	0.3	-10000	0	-0.59	159	159
IRS2/Crk	-0.11	0.18	-10000	0	-0.29	160	160
PI3K	-0.098	0.16	-10000	0	-0.26	160	160
apoptosis	0.047	0.12	0.36	6	-10000	0	6
HRAS/GDP	0.012	0	-10000	0	-10000	0	0
PRKCD	-0.14	0.21	-10000	0	-0.37	160	160
RAF1/14-3-3 E	-0.04	0.12	-10000	0	-0.35	7	7
BAD/14-3-3	-0.05	0.13	-10000	0	-0.38	6	6
PRKCZ	-0.076	0.14	-10000	0	-0.47	8	8
Crk/p130 Cas/Paxillin/FAK1	-0.08	0.092	-10000	0	-0.38	6	6
PTPN1	0.016	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.16	0.22	-10000	0	-0.4	160	160
BCAR1	0.016	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.11	0.16	-10000	0	-0.28	162	162
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.016	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.11	0.16	-10000	0	-0.29	160	160
GRB10	0.009	0.062	-10000	0	-0.58	4	4
PTPN11	-0.11	0.16	-10000	0	-0.29	160	160
IRS1	-0.13	0.18	-10000	0	-0.32	163	163
IRS2	-0.13	0.18	-10000	0	-0.32	160	160
IGF-1R heterotetramer/IGF1	-0.18	0.23	-10000	0	-0.44	160	160
GRB2	0.016	0	-10000	0	-10000	0	0
PDPK1	-0.086	0.15	-10000	0	-0.49	6	6
YWHAE	0.014	0.031	-10000	0	-0.58	1	1
PRKD1	-0.15	0.23	-10000	0	-0.4	161	161
SHC1	0.014	0.028	-10000	0	-0.51	1	1

×

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

Figure S12. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S12. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	-0.058	0.19	-10000	0	-0.4	81	81
CRKL	-0.062	0.2	-10000	0	-0.42	80	80
HRAS	-0.061	0.21	-10000	0	-0.5	37	37
mol:PIP3	-0.072	0.18	-10000	0	-0.4	80	80
SPRED1	0.016	0	-10000	0	-10000	0	0
SPRED2	0.016	0	-10000	0	-10000	0	0
GAB1	-0.072	0.2	-10000	0	-0.44	81	81
FOXO3	-0.05	0.18	-10000	0	-0.38	80	80
AKT1	-0.063	0.19	-10000	0	-0.41	80	80
BAD	-0.05	0.18	-10000	0	-0.38	80	80
megakaryocyte differentiation	-0.077	0.21	-10000	0	-0.43	84	84
GSK3B	-0.05	0.18	-10000	0	-0.38	80	80
RAF1	-0.038	0.18	-10000	0	-0.41	31	31
SHC1	0.014	0.028	-10000	0	-0.51	1	1
STAT3	-0.072	0.2	-10000	0	-0.44	81	81
STAT1	-0.2	0.47	-10000	0	-1	87	87
HRAS/SPRED1	-0.04	0.17	-10000	0	-0.41	31	31
cell proliferation	-0.072	0.21	-10000	0	-0.44	80	80
PIK3CA	0.015	0.001	-10000	0	-10000	0	0
TEC	0.016	0	-10000	0	-10000	0	0
RPS6KB1	-0.072	0.2	-10000	0	-0.44	81	81
HRAS/SPRED2	-0.04	0.17	-10000	0	-0.41	31	31
LYN/TEC/p62DOK	-0.095	0.17	-10000	0	-0.4	80	80
MAPK3	-0.011	0.13	-10000	0	-0.29	24	24
STAP1	-0.091	0.22	-10000	0	-0.46	82	82
GRAP2	-0.057	0.19	-10000	0	-0.58	44	44
JAK2	-0.2	0.37	-10000	0	-0.84	87	87
STAT1 (dimer)	-0.19	0.46	-10000	0	-0.98	87	87
mol:Gleevec	0.001	0.008	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.11	0.18	-10000	0	-0.42	83	83
actin filament polymerization	-0.074	0.2	-10000	0	-0.43	82	82
LYN	0.016	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.11	0.29	-10000	0	-0.62	82	82
PIK3R1	0.015	0.001	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.04	0.18	-10000	0	-0.37	80	80
PI3K	-0.054	0.2	-10000	0	-0.41	80	80
PTEN	0.016	0	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.25	0.57	-10000	0	-1.3	82	82
MAPK8	-0.074	0.21	-10000	0	-0.45	80	80
STAT3 (dimer)	-0.07	0.2	-10000	0	-0.43	81	81
positive regulation of transcription	-0.004	0.11	-10000	0	-0.24	19	19
mol:GDP	-0.11	0.2	-10000	0	-0.41	90	90
PIK3C2B	-0.072	0.2	-10000	0	-0.44	81	81
CBL/CRKL	-0.049	0.19	-10000	0	-0.38	80	80
FER	-0.074	0.21	-10000	0	-0.44	81	81
SH2B3	-0.072	0.2	-10000	0	-0.44	81	81
PDPK1	-0.059	0.17	-10000	0	-0.36	80	80
SNAI2	-0.078	0.21	-10000	0	-0.45	81	81
positive regulation of cell proliferation	-0.13	0.34	-10000	0	-0.72	87	87
KITLG	0.009	0.065	-10000	0	-0.6	4	4
cell motility	-0.13	0.34	-10000	0	-0.72	87	87
PTPN6	0.016	0.03	-10000	0	-0.52	1	1
EPOR	-0.023	0.15	-10000	0	-0.56	2	2
STAT5A (dimer)	-0.1	0.29	-10000	0	-0.6	87	87
SOCS1	0.014	0.028	-10000	0	-0.51	1	1
cell migration	0.093	0.22	0.46	85	-10000	0	85
SOS1	0.016	0	-10000	0	-10000	0	0
EPO	-0.033	0.14	-10000	0	-0.51	30	30
VAV1	-0.014	0.13	-10000	0	-0.57	18	18
GRB10	-0.075	0.21	-10000	0	-0.45	81	81
PTPN11	0.017	0.008	-10000	0	-10000	0	0
SCF/KIT	-0.085	0.22	-10000	0	-0.46	84	84
GO:0007205	0.003	0.011	-10000	0	-10000	0	0
MAP2K1	-0.018	0.14	-10000	0	-0.31	29	29
CBL	0.016	0	-10000	0	-10000	0	0
KIT	-0.26	0.59	-10000	0	-1.4	80	80
MAP2K2	-0.018	0.14	-10000	0	-0.32	24	24
SHC/Grb2/SOS1	-0.095	0.17	-10000	0	-0.4	80	80
STAT5A	-0.11	0.3	-10000	0	-0.62	87	87
GRB2	0.016	0	-10000	0	-10000	0	0
response to radiation	-0.076	0.21	-10000	0	-0.44	81	81
SHC/GRAP2	-0.032	0.14	-10000	0	-0.41	45	45
PTPRO	-0.079	0.21	-10000	0	-0.44	84	84
SH2B2	-0.076	0.21	-10000	0	-0.44	82	82
DOK1	0.014	0.028	-10000	0	-0.51	1	1
MATK	-0.096	0.22	-10000	0	-0.47	85	85
CREBBP	0.034	0.02	-10000	0	-10000	0	0
BCL2	-0.061	0.31	-10000	0	-1.4	14	14

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.002	0.087	-9999	-0.36	20	20
VLDLR	-0.001	0.098	-9999	-0.58	10	10
CRKL	0.013	0.039	-9999	-0.51	2	2
LRPAP1	0.014	0.028	-9999	-0.51	1	1
FYN	0.011	0.054	-9999	-0.58	3	3
ITGA3	0.008	0.061	-9999	-0.51	5	5
RELN/VLDLR/Fyn	-0.12	0.19	-9999	-0.35	141	141
MAPK8IP1/MKK7/MAP3K11/JNK1	0.04	0.044	-9999	-10000	0	0
AKT1	-0.095	0.16	-9999	-0.44	24	24
MAP2K7	0.016	0	-9999	-10000	0	0
RAPGEF1	0.016	0	-9999	-10000	0	0
DAB1	-0.07	0.2	-9999	-0.55	51	51
RELN/LRP8/DAB1	-0.2	0.23	-9999	-0.38	192	192
LRPAP1/LRP8	-0.048	0.15	-9999	-0.36	67	67
RELN/LRP8/DAB1/Fyn	-0.18	0.22	-9999	-0.39	153	153
DAB1/alpha3/beta1 Integrin	-0.18	0.19	-9999	-0.52	63	63
long-term memory	-0.23	0.27	-9999	-0.61	91	91
DAB1/LIS1	-0.18	0.2	-9999	-0.53	60	60
DAB1/CRLK/C3G	-0.18	0.19	-9999	-0.51	61	61
PIK3CA	0.016	0	-9999	-10000	0	0
DAB1/NCK2	-0.18	0.2	-9999	-0.54	60	60
ARHGEF2	0.016	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.12	0.24	-9999	-0.57	77	77
CDK5R1	-0.014	0.12	-9999	-0.51	20	20
RELN	-0.2	0.28	-9999	-0.57	131	131
PIK3R1	0.016	0	-9999	-10000	0	0
RELN/LRP8/Fyn	-0.17	0.22	-9999	-0.38	169	169
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.24	0.27	-9999	-0.64	87	87
MAPK8	0.011	0.054	-9999	-0.58	3	3
RELN/VLDLR/DAB1	-0.15	0.2	-9999	-0.35	168	168
ITGB1	0.016	0	-9999	-10000	0	0
MAP1B	-0.21	0.24	-9999	-0.43	160	160
RELN/LRP8	-0.16	0.22	-9999	-0.4	141	141
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.18	0.22	-9999	-0.58	55	55
PI3K	0.023	0	-9999	-10000	0	0
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	0.018	0.044	-9999	-0.36	5	5
RAP1A	-0.14	0.2	-9999	-0.48	61	61
PAFAH1B1	0.016	0	-9999	-10000	0	0
MAPK8IP1	0.009	0.061	-9999	-0.56	4	4
CRLK/C3G	0.021	0.028	-9999	-0.36	2	2
GRIN2B	-0.01	0.089	-9999	-0.51	11	11
NCK2	0.016	0	-9999	-10000	0	0
neuron differentiation	-0.079	0.14	-9999	-0.32	53	53
neuron adhesion	-0.12	0.2	-9999	-0.45	64	64
LRP8	-0.081	0.2	-9999	-0.51	66	66
GSK3B	-0.082	0.15	-9999	-0.41	24	24
RELN/VLDLR/DAB1/Fyn	-0.14	0.19	-9999	-0.34	156	156
MAP3K11	0.016	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.11	0.16	-9999	-0.29	153	153
CDK5	0.016	0	-9999	-10000	0	0
MAPT	-0.023	0.16	-9999	-0.52	32	32
neuron migration	-0.14	0.21	-9999	-0.46	64	64
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.08	0.14	-9999	-0.32	53	53
RELN/VLDLR	-0.15	0.21	-9999	-0.56	38	38

×

TCGA08_p53

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
CDKN2A	-0.17	0.19	-10000	0	-0.37	174	174
TP53	-0.041	0.061	-10000	0	-10000	0	0
Senescence	-0.041	0.06	-10000	0	-10000	0	0
Apoptosis	-0.041	0.06	-10000	0	-10000	0	0
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.078	0.12	0.19	168	-0.33	12	180
MDM4	0.016	0	-10000	0	-10000	0	0

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	-0.017	0.13	-10000	0	-0.55	20	20
GNB1/GNG2	-0.079	0.09	-10000	0	-0.18	145	145
AKT1	-0.042	0.13	-10000	0	-0.2	75	75
EGF	-0.018	0.12	-10000	0	-0.51	22	22
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.036	0.057	-10000	0	-0.37	1	1
mol:Ca2+	-0.085	0.18	-10000	0	-0.3	143	143
LYN	0.036	0.056	-10000	0	-0.37	1	1
RhoA/GTP	-0.051	0.059	-10000	0	-0.14	20	20
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.097	0.21	-10000	0	-0.34	143	143
GNG2	0.006	0.076	-10000	0	-0.58	6	6
ARRB2	0.016	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.015	0.071	-10000	0	-0.36	4	4
G beta5/gamma2	-0.1	0.12	-10000	0	-0.24	145	145
PRKCH	-0.099	0.21	-10000	0	-0.34	143	143
DNM1	0.001	0.093	-10000	0	-0.58	9	9
TXA2/TP beta/beta Arrestin3	-0.008	0.039	-10000	0	-0.24	9	9
mol:GTP	0	0.002	-10000	0	-10000	0	0
PTGDR	-0.016	0.13	-10000	0	-0.58	18	18
G12 family/GTP	-0.13	0.14	-10000	0	-0.3	143	143
ADRBK1	0.015	0	-10000	0	-10000	0	0
ADRBK2	0.012	0.042	-10000	0	-0.54	2	2
RhoA/GTP/ROCK1	0.012	0.011	-10000	0	-10000	0	0
mol:GDP	0.037	0.12	0.31	13	-10000	0	13
mol:NADP	0.014	0.028	-10000	0	-0.51	1	1
RAB11A	0.016	0	-10000	0	-10000	0	0
PRKG1	-0.12	0.25	-10000	0	-0.58	82	82
mol:IP3	-0.11	0.22	-10000	0	-0.38	143	143
cell morphogenesis	0.01	0.011	-10000	0	-10000	0	0
PLCB2	-0.16	0.3	-10000	0	-0.51	143	143
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	0	0.097	-10000	0	-0.4	3	3
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.024	0.085	-10000	0	-0.4	6	6
RHOA	0.016	0	-10000	0	-10000	0	0
PTGIR	0.014	0.031	-10000	0	-0.58	1	1
PRKCB1	-0.11	0.22	-10000	0	-0.37	143	143
GNAQ	0.016	0	-10000	0	-10000	0	0
mol:L-citrulline	0.014	0.028	-10000	0	-0.51	1	1
TXA2/TXA2-R family	-0.17	0.3	-10000	0	-0.53	143	143
LCK	0.032	0.066	-10000	0	-0.4	2	2
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.012	0.049	-10000	0	-10000	0	0
TXA2-R family/G12 family/GDP/G beta/gamma	0.031	0.032	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.012	0.048	-10000	0	-10000	0	0
MAPK14	-0.052	0.15	-10000	0	-0.22	143	143
TGM2/GTP	-0.13	0.26	-10000	0	-0.43	143	143
MAPK11	-0.052	0.15	-10000	0	-0.22	143	143
ARHGEF1	-0.04	0.11	-10000	0	-0.18	100	100
GNAI2	0.016	0	-10000	0	-10000	0	0
JNK cascade	-0.12	0.23	-10000	0	-0.39	143	143
RAB11/GDP	0.016	0.002	-10000	0	-10000	0	0
ICAM1	-0.077	0.17	-10000	0	-0.28	145	145
cAMP biosynthetic process	-0.11	0.21	-10000	0	-0.36	143	143
Gq family/GTP/EBP50	-0.005	0.087	-10000	0	-0.28	11	11
actin cytoskeleton reorganization	0.01	0.011	-10000	0	-10000	0	0
SRC	0.036	0.056	-10000	0	-0.37	1	1
GNB5	0.015	0	-10000	0	-10000	0	0
GNB1	0.016	0	-10000	0	-10000	0	0
EGF/EGFR	0.035	0.075	-10000	0	-0.31	2	2
VCAM1	-0.088	0.19	-10000	0	-0.31	143	143
TP beta/Gq family/GDP/G beta5/gamma2	0.015	0.071	-10000	0	-0.36	4	4
platelet activation	-0.072	0.2	-10000	0	-0.3	143	143
PGI2/IP	0.009	0.023	-10000	0	-0.42	1	1
PRKACA	0.008	0.067	-10000	0	-0.27	19	19
Gq family/GDP/G beta5/gamma2	0.013	0.072	-10000	0	-0.33	4	4
TXA2/TP beta/beta Arrestin2	-0.015	0.085	-10000	0	-0.54	9	9
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.015	0.066	-10000	0	-0.25	21	21
mol:DAG	-0.13	0.25	-10000	0	-0.42	143	143
EGFR	-0.008	0.11	-10000	0	-0.54	15	15
TXA2/TP alpha	-0.15	0.28	-10000	0	-0.48	143	143
Gq family/GTP	-0.032	0.083	-10000	0	-0.23	53	53
YES1	0.036	0.056	-10000	0	-0.37	1	1
GNAI2/GTP	-0.012	0.05	-10000	0	-0.43	1	1
PGD2/DP	-0.013	0.095	-10000	0	-0.42	18	18
SLC9A3R1	-0.012	0.12	-10000	0	-0.51	19	19
FYN	0.034	0.063	-10000	0	-0.4	2	2
mol:NO	0.014	0.028	-10000	0	-0.51	1	1
GNA15	0.012	0.044	-10000	0	-0.58	2	2
PGK/cGMP	-0.067	0.16	-10000	0	-0.35	83	83
RhoA/GDP	0.016	0.002	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0.018	0.11	-10000	0	-0.55	6	6
NOS3	0.014	0.028	-10000	0	-0.51	1	1
RAC1	0.016	0	-10000	0	-10000	0	0
PRKCA	-0.1	0.21	-10000	0	-0.34	143	143
PRKCB	-0.15	0.24	-10000	0	-0.42	147	147
PRKCE	-0.095	0.21	-10000	0	-0.34	143	143
PRKCD	-0.11	0.23	-10000	0	-0.38	143	143
PRKCG	-0.12	0.23	-10000	0	-0.39	143	143
muscle contraction	-0.16	0.29	-10000	0	-0.49	143	143
PRKCZ	-0.097	0.21	-10000	0	-0.34	143	143
ARR3	0.003	0.006	-10000	0	-10000	0	0
TXA2/TP beta	0.011	0.066	-10000	0	-0.49	1	1
PRKCQ	-0.11	0.22	-10000	0	-0.37	144	144
MAPKKK cascade	-0.15	0.27	-10000	0	-0.46	143	143
SELE	-0.13	0.24	-10000	0	-0.41	145	145
TP beta/GNAI2/GDP/G beta/gamma	0.033	0.071	-10000	0	-0.48	1	1
ROCK1	0.016	0	-10000	0	-10000	0	0
GNA14	-0.067	0.2	-10000	0	-0.58	50	50
chemotaxis	-0.2	0.35	-10000	0	-0.62	143	143
GNA12	0.016	0	-10000	0	-10000	0	0
GNA13	0.016	0	-10000	0	-10000	0	0
GNA11	0.014	0.031	-10000	0	-0.58	1	1
Rac1/GTP	0.007	0.006	-10000	0	-10000	0	0

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.014	0.028	-9999	-0.51	1	1
Aurora C/Aurora B/INCENP	-0.11	0.15	-9999	-0.27	169	169
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.035	0.037	-9999	-10000	0	0
AURKB	-0.22	0.26	-9999	-0.51	161	161
AURKC	-0.001	0.09	-9999	-0.51	11	11

×

TCGA08_retinoblastoma

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
CDKN2B	-0.034	0.16	-10000	0	-0.54	32	32
CDKN2C	0.039	0.039	-10000	0	-0.45	1	1
CDKN2A	-0.25	0.27	-10000	0	-0.52	174	174
CCND2	0.053	0.081	0.23	33	-0.15	9	42
RB1	-0.051	0.088	0.16	2	-0.24	32	34
CDK4	0.068	0.082	0.24	34	-10000	0	34
CDK6	0.059	0.089	0.25	32	-0.19	7	39
G1/S progression	0.051	0.088	0.24	32	-0.16	2	34

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.014	0.031	-9999	-0.58	1	1
LAT2	-0.1	0.19	-9999	-0.35	110	110
AP1	-0.2	0.22	-9999	-0.52	96	96
mol:PIP3	-0.12	0.24	-9999	-0.5	69	69
IKBKB	-0.077	0.15	-9999	-0.29	94	94
AKT1	-0.078	0.18	-9999	-0.43	50	50
IKBKG	-0.077	0.15	-9999	-0.29	92	92
MS4A2	-0.15	0.26	-9999	-0.58	99	99
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.015	0.001	-9999	-10000	0	0
MAP3K1	-0.073	0.19	-9999	-0.41	61	61
mol:Ca2+	-0.084	0.18	-9999	-0.37	69	69
LYN	0.013	0.006	-9999	-10000	0	0
CBLB	-0.098	0.19	-9999	-0.34	107	107
SHC1	0.014	0.028	-9999	-0.51	1	1
RasGAP/p62DOK	-0.069	0.16	-9999	-0.32	102	102
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0.004	0.082	-9999	-0.58	7	7
PLD2	-0.12	0.21	-9999	-0.4	98	98
PTPN13	-0.098	0.2	-9999	-0.48	52	52
PTPN11	0.012	0.009	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.048	0.16	-9999	-0.34	47	47
SYK	0.01	0.046	-9999	-0.6	2	2
GRB2	0.015	0.001	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.16	0.21	-9999	-0.53	67	67
LAT	-0.099	0.19	-9999	-0.44	58	58
PAK2	-0.09	0.21	-9999	-0.46	61	61
NFATC2	-0.16	0.26	-9999	-0.7	63	63
HRAS	-0.11	0.23	-9999	-0.5	63	63
GAB2	0.016	0	-9999	-10000	0	0
PLA2G1B	0.042	0.023	-9999	-10000	0	0
Fc epsilon R1	-0.19	0.24	-9999	-0.43	158	158
Antigen/IgE/Fc epsilon R1	-0.17	0.22	-9999	-0.4	158	158
mol:GDP	-0.12	0.24	-9999	-0.54	64	64
JUN	-0.006	0.11	-9999	-0.58	13	13
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.015	0.001	-9999	-10000	0	0
FOS	-0.17	0.27	-9999	-0.58	110	110
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.11	0.2	-9999	-0.37	107	107
CHUK	-0.077	0.15	-9999	-0.29	93	93
KLRG1	-0.096	0.18	-9999	-0.42	57	57
VAV1	-0.11	0.21	-9999	-0.47	64	64
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.098	0.19	-9999	-0.44	56	56
negative regulation of mast cell degranulation	-0.087	0.18	-9999	-0.42	56	56
BTK	-0.13	0.26	-9999	-0.59	62	62
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.16	0.27	-9999	-0.48	109	109
GAB2/PI3K/SHP2	-0.13	0.17	-9999	-0.48	50	50
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.12	0.22	-9999	-0.52	61	61
RAF1	0.03	0.028	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.18	0.24	-9999	-0.59	69	69
FCER1G	-0.005	0.11	-9999	-0.53	16	16
FCER1A	-0.14	0.26	-9999	-0.59	92	92
Antigen/IgE/Fc epsilon R1/Fyn	-0.16	0.21	-9999	-0.37	153	153
MAPK3	0.04	0.023	-9999	-10000	0	0
MAPK1	0.04	0.023	-9999	-10000	0	0
NFKB1	0.016	0	-9999	-10000	0	0
MAPK8	-0.011	0.083	-9999	-0.59	3	3
DUSP1	-0.15	0.27	-9999	-0.58	102	102
NF-kappa-B/RelA	-0.062	0.071	-9999	-0.22	11	11
actin cytoskeleton reorganization	-0.1	0.2	-9999	-0.48	48	48
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.13	0.18	-9999	-0.46	58	58
FER	-0.1	0.19	-9999	-0.45	57	57
RELA	0.016	0	-9999	-10000	0	0
ITK	-0.085	0.17	-9999	-0.52	43	43
SOS1	0.016	0	-9999	-10000	0	0
PLCG1	-0.12	0.24	-9999	-0.54	64	64
cytokine secretion	-0.045	0.051	-9999	-10000	0	0
SPHK1	-0.13	0.2	-9999	-0.46	71	71
PTK2	-0.11	0.2	-9999	-0.5	48	48
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.17	0.22	-9999	-0.55	68	68
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.11	0.23	-9999	-0.5	67	67
MAP2K2	0.036	0.024	-9999	-10000	0	0
MAP2K1	0.036	0.024	-9999	-10000	0	0
MAP2K7	0.016	0	-9999	-10000	0	0
KLRG1/SHP2	-0.11	0.15	-9999	-0.4	53	53
MAP2K4	0.019	0.012	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.2	0.24	-9999	-0.42	161	161
mol:Choline	-0.12	0.21	-9999	-0.4	98	98
SHC/Grb2/SOS1	-0.11	0.16	-9999	-0.44	48	48
FYN	0.011	0.054	-9999	-0.58	3	3
DOK1	0.014	0.028	-9999	-0.51	1	1
PXN	-0.092	0.19	-9999	-0.46	47	47
HCLS1	-0.1	0.19	-9999	-0.45	57	57
PRKCB	-0.12	0.21	-9999	-0.4	102	102
FCGR2B	-0.032	0.16	-9999	-0.57	29	29
IGHE	-0.003	0.007	-9999	-10000	0	0
KLRG1/SHIP	-0.088	0.18	-9999	-0.43	56	56
LCP2	0.012	0.044	-9999	-0.58	2	2
PLA2G4A	-0.12	0.21	-9999	-0.44	77	77
RASA1	0.016	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.12	0.21	-9999	-0.4	98	98
IKK complex	-0.043	0.12	-9999	-0.22	56	56
WIPF1	-0.003	0.1	-9999	-0.58	11	11

×

p75(NTR)-mediated 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
Sortilin/TRAF6	0.023	0	-10000	0	-10000	0	0
Necdin/E2F1	-0.12	0.21	-10000	0	-0.41	113	113
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.074	0.19	-10000	0	-0.6	20	20
NGF (dimer)/p75(NTR)/BEX1	-0.14	0.24	-10000	0	-0.42	133	133
NT-4/5 (dimer)/p75(NTR)	-0.11	0.22	-10000	0	-0.45	99	99
IKBKB	0.016	0	-10000	0	-10000	0	0
AKT1	-0.071	0.18	-10000	0	-0.57	18	18
IKBKG	0.016	0	-10000	0	-10000	0	0
BDNF	-0.099	0.23	-10000	0	-0.58	69	69
MGDIs/NGR/p75(NTR)/LINGO1	-0.12	0.2	-10000	0	-0.36	135	135
FURIN	0.014	0.028	-10000	0	-0.51	1	1
proBDNF (dimer)/p75(NTR)/Sortilin	-0.13	0.22	-10000	0	-0.39	133	133
LINGO1	-0.008	0.11	-10000	0	-0.51	16	16
Sortilin/TRAF6/NRIF	0	0	-10000	0	-10000	0	0
proBDNF (dimer)	-0.099	0.23	-10000	0	-0.57	69	69
NTRK1	0.006	0.061	-10000	0	-0.51	5	5
RTN4R	-0.061	0.18	-10000	0	-0.51	52	52
neuron apoptosis	-0.12	0.22	-10000	0	-0.52	54	54
IRAK1	0.016	0	-10000	0	-10000	0	0
SHC1	-0.1	0.21	-10000	0	-0.4	113	113
ARHGDIA	0.016	0	-10000	0	-10000	0	0
RhoA/GTP	0.012	0	-10000	0	-10000	0	0
Gamma Secretase	0.046	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.086	0.2	-10000	0	-0.36	109	109
MAGEH1	0.012	0.044	-10000	0	-0.58	2	2
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.12	0.24	-10000	0	-0.41	129	129
Mammalian IAPs/DIABLO	0.014	0.095	-10000	0	-0.33	22	22
proNGF (dimer)	-0.063	0.2	-10000	0	-0.57	47	47
MAGED1	0.016	0	-10000	0	-10000	0	0
APP	0.012	0.044	-10000	0	-0.58	2	2
NT-4/5 (dimer)	-0.026	0.15	-10000	0	-0.57	25	25
ZNF274	0.016	0	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.079	0.18	-10000	0	-0.33	109	109
NGF	-0.063	0.2	-10000	0	-0.58	47	47
cell cycle arrest	-0.085	0.17	-10000	0	-0.45	29	29
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.058	0.16	-10000	0	-0.43	25	25
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.081	0.19	-10000	0	-0.38	99	99
NCSTN	0.016	0	-10000	0	-10000	0	0
mol:GTP	-0.1	0.21	-10000	0	-0.39	115	115
PSENEN	0.016	0	-10000	0	-10000	0	0
mol:ceramide	-0.084	0.19	-10000	0	-0.35	109	109
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.038	0.14	-10000	0	-0.42	19	19
p75(NTR)/beta APP	-0.081	0.19	-10000	0	-0.42	85	85
BEX1	-0.045	0.17	-10000	0	-0.56	36	36
mol:GDP	-0.11	0.21	-10000	0	-0.4	113	113
NGF (dimer)	-0.09	0.17	-10000	0	-0.31	127	127
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.095	0.18	-10000	0	-0.35	86	86
PIK3R1	0.016	0	-10000	0	-10000	0	0
RAC1/GTP	-0.089	0.18	-10000	0	-0.34	113	113
MYD88	0.016	0	-10000	0	-10000	0	0
CHUK	0.016	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.1	0.21	-10000	0	-0.39	115	115
RHOB	0.016	0	-10000	0	-10000	0	0
RHOA	0.016	0	-10000	0	-10000	0	0
MAGE-G1/E2F1	-0.063	0.16	-10000	0	-0.36	81	81
NT3 (dimer)	-0.092	0.23	-10000	0	-0.57	65	65
TP53	-0.078	0.18	-10000	0	-0.55	20	20
PRDM4	-0.085	0.19	-10000	0	-0.35	109	109
BDNF (dimer)	-0.17	0.23	-10000	0	-0.37	171	171
PIK3CA	0.016	0	-10000	0	-10000	0	0
SORT1	0.016	0	-10000	0	-10000	0	0
activation of caspase activity	-0.1	0.17	-10000	0	-0.59	20	20
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.084	0.19	-10000	0	-0.36	109	109
RHOC	0.016	0	-10000	0	-10000	0	0
XIAP	0.012	0.042	-10000	0	-0.54	2	2
MAPK10	-0.1	0.22	-10000	0	-0.53	50	50
DIABLO	0.016	0	-10000	0	-10000	0	0
SMPD2	-0.085	0.19	-10000	0	-0.35	109	109
APH1B	0.016	0	-10000	0	-10000	0	0
APH1A	0.016	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.1	0.21	-10000	0	-0.39	113	113
PSEN1	0.016	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.023	0	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.15	0.25	-10000	0	-0.47	128	128
MAPK8	-0.085	0.21	-10000	0	-0.52	41	41
MAPK9	-0.083	0.21	-10000	0	-0.52	41	41
APAF1	0.016	0	-10000	0	-10000	0	0
NTF3	-0.093	0.23	-10000	0	-0.57	65	65
NTF4	-0.026	0.15	-10000	0	-0.58	25	25
NDN	-0.059	0.2	-10000	0	-0.58	45	45
RAC1/GDP	0.012	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.095	0.15	-10000	0	-0.54	18	18
p75 CTF/Sortilin/TRAF6/NRIF	0.04	0	-10000	0	-10000	0	0
RhoA-B-C/GTP	-0.12	0.2	-10000	0	-0.39	115	115
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.091	0.19	-10000	0	-0.58	20	20
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.1	0.2	-10000	0	-0.35	129	129
PRKACB	0.012	0.044	-10000	0	-0.58	2	2
proBDNF (dimer)/p75 ECD	-0.061	0.17	-10000	0	-0.41	69	69
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.024	0.15	-10000	0	-0.57	24	24
BIRC2	0.013	0.039	-10000	0	-0.51	2	2
neuron projection morphogenesis	-0.12	0.21	0.2	13	-0.4	101	114
BAD	-0.086	0.21	-10000	0	-0.5	47	47
RIPK2	0.016	0	-10000	0	-10000	0	0
NGFR	-0.12	0.25	-10000	0	-0.57	84	84
CYCS	-0.071	0.18	-10000	0	-0.57	18	18
ADAM17	0.016	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.084	0.19	-10000	0	-0.36	109	109
BCL2L11	-0.086	0.21	-10000	0	-0.5	47	47
BDNF (dimer)/p75(NTR)	-0.16	0.25	-10000	0	-0.46	133	133
PI3K	-0.084	0.19	-10000	0	-0.36	109	109
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.084	0.19	-10000	0	-0.36	109	109
NDNL2	0.016	0	-10000	0	-10000	0	0
YWHAE	0.014	0.031	-10000	0	-0.58	1	1
PRKCI	0.016	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.13	0.24	-10000	0	-0.47	113	113
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.084	0.19	-10000	0	-0.36	109	109
TRAF6	0.016	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
PRKCZ	0.012	0.044	-10000	0	-0.58	2	2
PLG	-0.003	0.06	-10000	0	-0.51	5	5
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.14	0.25	-10000	0	-0.48	91	91
SQSTM1	0.016	0	-10000	0	-10000	0	0
NGFRAP1	0.012	0.044	-10000	0	-0.58	2	2
CASP3	-0.077	0.2	-10000	0	-0.45	47	47
E2F1	-0.1	0.22	-10000	0	-0.51	81	81
CASP9	0.016	0	-10000	0	-10000	0	0
IKK complex	-0.076	0.13	-10000	0	-0.49	19	19
NGF (dimer)/TRKA	-0.042	0.15	-10000	0	-0.41	52	52
MMP7	-0.11	0.23	-10000	0	-0.52	85	85
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.071	0.18	-10000	0	-0.58	18	18
MMP3	-0.1	0.23	-10000	0	-0.55	74	74
APAF-1/Caspase 9	-0.085	0.13	-10000	0	-0.44	28	28

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0.051	0.066	0.13	152	-10000	0	152
BUB1B	-0.078	0.12	-10000	0	-0.23	114	114
PLK1	-0.019	0.05	-10000	0	-0.11	64	64
PLK1S1	-0.003	0.026	-10000	0	-10000	0	0
KIF2A	-0.008	0.045	-10000	0	-0.18	1	1
regulation of mitotic centrosome separation	-0.019	0.05	-10000	0	-0.11	64	64
GOLGA2	0.016	0	-10000	0	-10000	0	0
Hec1/SPC24	-0.18	0.24	-10000	0	-0.41	165	165
WEE1	-0.016	0.054	-10000	0	-10000	0	0
cytokinesis	-0.14	0.11	-10000	0	-0.24	126	126
PP2A-alpha B56	0.018	0.038	-10000	0	-10000	0	0
AURKA	-0.018	0.047	-10000	0	-0.13	2	2
PICH/PLK1	-0.11	0.19	-10000	0	-0.37	97	97
CENPE	-0.068	0.14	-10000	0	-0.33	77	77
RhoA/GTP	0.012	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.008	0.045	-10000	0	-0.18	1	1
PPP2CA	0.016	0	-10000	0	-10000	0	0
FZR1	0.016	0	-10000	0	-10000	0	0
TPX2	-0.037	0.051	-10000	0	-0.1	79	79
PAK1	0.013	0.032	-10000	0	-0.59	1	1
SPC24	-0.17	0.25	-10000	0	-0.51	126	126
FBXW11	0.016	0	-10000	0	-10000	0	0
CLSPN	-0.033	0.057	-10000	0	-0.13	54	54
GORASP1	0.016	0	-10000	0	-10000	0	0
metaphase	-0.002	0.004	-10000	0	-0.011	62	62
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	-0.009	0.026	-10000	0	-0.054	64	64
G2 phase of mitotic cell cycle	-0.002	0.003	-10000	0	-0.009	1	1
STAG2	0.012	0.044	-10000	0	-0.58	2	2
GRASP65/GM130/RAB1/GTP	0.006	0.011	-10000	0	-10000	0	0
spindle elongation	-0.019	0.05	-10000	0	-0.11	64	64
ODF2	0.013	0.003	-10000	0	-10000	0	0
BUB1	-0.015	0.034	-10000	0	-10000	0	0
TPT1	-0.003	0.026	-10000	0	-0.097	1	1
CDC25C	-0.056	0.059	-10000	0	-10000	0	0
CDC25B	0.005	0.068	-10000	0	-0.51	6	6
SGOL1	-0.051	0.066	-10000	0	-0.13	152	152
RHOA	0.016	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.074	0.11	-10000	0	-0.26	42	42
CDC14B	0.011	0.024	-10000	0	-0.43	1	1
CDC20	-0.28	0.26	-10000	0	-0.51	204	204
PLK1/PBIP1	-0.03	0.057	-10000	0	-0.28	12	12
mitosis	-0.001	0.01	0.021	21	-0.019	7	28
FBXO5	-0.011	0.047	-10000	0	-0.23	3	3
CDC2	-0.003	0.005	-10000	0	-0.012	44	44
NDC80	-0.15	0.24	-10000	0	-0.51	115	115
metaphase plate congression	-0.008	0.032	-10000	0	-10000	0	0
ERCC6L	-0.093	0.17	-10000	0	-0.44	49	49
NLP/gamma Tubulin	-0.005	0.027	-10000	0	-0.097	2	2
microtubule cytoskeleton organization	-0.003	0.026	-10000	0	-0.097	1	1
G2/M transition DNA damage checkpoint	-0.001	0.002	-10000	0	-10000	0	0
PPP1R12A	0.015	0.001	-10000	0	-10000	0	0
interphase	-0.001	0.002	-10000	0	-10000	0	0
PLK1/PRC1-2	-0.25	0.2	-10000	0	-0.34	268	268
GRASP65/GM130/RAB1/GTP/PLK1	-0.009	0.027	-10000	0	-10000	0	0
RAB1A	0.016	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	-0.013	0.048	-10000	0	-0.22	2	2
mitotic prometaphase	-0.003	0.003	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.015	0.051	-10000	0	-0.3	1	1
microtubule-based process	-0.22	0.15	-10000	0	-0.3	266	266
Golgi organization	-0.019	0.05	-10000	0	-0.11	64	64
Cohesin/SA2	-0.025	0.039	-10000	0	-0.25	3	3
PPP1CB/MYPT1	0.017	0.009	-10000	0	-10000	0	0
KIF20A	-0.37	0.23	-10000	0	-0.51	266	266
APC/C/CDC20	-0.17	0.17	-10000	0	-0.31	204	204
PPP2R1A	0.016	0	-10000	0	-10000	0	0
chromosome segregation	-0.03	0.057	-10000	0	-0.28	12	12
PRC1	-0.084	0.2	-10000	0	-0.51	68	68
ECT2	-0.037	0.11	-10000	0	-0.34	38	38
C13orf34	-0.01	0.045	-10000	0	-0.22	2	2
NUDC	-0.008	0.032	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.077	0.12	-10000	0	-0.23	114	114
spindle assembly	-0.011	0.04	-10000	0	-0.099	8	8
spindle stabilization	-0.003	0.026	-10000	0	-10000	0	0
APC/C/HCDH1	0.019	0.02	-10000	0	-0.36	1	1
MKLP2/PLK1	-0.22	0.15	-10000	0	-0.3	266	266
CCNB1	-0.16	0.25	-10000	0	-0.5	123	123
PPP1CB	0.015	0.001	-10000	0	-10000	0	0
BTRC	0.016	0	-10000	0	-10000	0	0
ROCK2	-0.008	0.069	-10000	0	-0.43	7	7
TUBG1	-0.003	0.026	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.075	0.1	-10000	0	-0.26	34	34
MLF1IP	-0.003	0.067	-10000	0	-0.38	11	11
INCENP	0.014	0.028	-10000	0	-0.51	1	1

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.34	0.54	-10000	0	-1.2	74	74
IL23A	-0.29	0.46	-10000	0	-1.1	60	60
NF kappa B1 p50/RelA/I kappa B alpha	-0.32	0.4	-10000	0	-1	73	73
positive regulation of T cell mediated cytotoxicity	-0.32	0.5	-10000	0	-1.1	74	74
ITGA3	-0.28	0.44	-10000	0	-1	65	65
IL17F	-0.18	0.31	-10000	0	-0.67	65	65
IL12B	-0.012	0.095	-10000	0	-0.51	11	11
STAT1 (dimer)	-0.31	0.48	-10000	0	-1.1	72	72
CD4	-0.28	0.44	-10000	0	-1	65	65
IL23	-0.29	0.44	-10000	0	-1.1	62	62
IL23R	-0.03	0.089	-10000	0	-10000	0	0
IL1B	-0.31	0.49	-10000	0	-1.1	66	66
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.3	0.44	-10000	0	-1	68	68
TYK2	0.008	0.021	-10000	0	-10000	0	0
STAT4	-0.016	0.13	-10000	0	-0.58	19	19
STAT3	0.016	0	-10000	0	-10000	0	0
IL18RAP	-0.018	0.13	-10000	0	-0.57	19	19
IL12RB1	-0.029	0.14	-10000	0	-0.55	24	24
PIK3CA	0.016	0	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	-0.02	0.11	-10000	0	-0.4	24	24
IL23R/JAK2	-0.035	0.11	-10000	0	-0.47	1	1
positive regulation of chronic inflammatory response	-0.32	0.5	-10000	0	-1.1	74	74
natural killer cell activation	0.003	0.008	-10000	0	-10000	0	0
JAK2	0.012	0.041	-10000	0	-0.61	1	1
PIK3R1	0.016	0	-10000	0	-10000	0	0
NFKB1	0.014	0.004	-10000	0	-10000	0	0
RELA	0.014	0.004	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.28	0.42	-10000	0	-0.99	63	63
ALOX12B	-0.29	0.44	-10000	0	-1	62	62
CXCL1	-0.34	0.52	-10000	0	-1.2	77	77
T cell proliferation	-0.32	0.5	-10000	0	-1.1	74	74
NFKBIA	0.014	0.004	-10000	0	-10000	0	0
IL17A	-0.12	0.25	-10000	0	-0.54	51	51
PI3K	-0.32	0.42	-10000	0	-1	74	74
IFNG	-0.017	0.035	0.1	1	-0.097	2	3
STAT3 (dimer)	-0.31	0.38	-10000	0	-0.98	70	70
IL18R1	0.009	0.054	-10000	0	-0.57	3	3
IL23/IL23R/JAK2/TYK2/SOCS3	-0.18	0.31	-10000	0	-0.73	53	53
IL18/IL18R	0.002	0.11	-10000	0	-0.38	24	24
macrophage activation	-0.018	0.017	-10000	0	-0.043	67	67
TNF	-0.29	0.46	-10000	0	-1.1	68	68
STAT3/STAT4	-0.34	0.43	-10000	0	-1	75	75
STAT4 (dimer)	-0.32	0.49	-10000	0	-1.1	74	74
IL18	0.006	0.069	-10000	0	-0.57	5	5
IL19	-0.29	0.44	-10000	0	-1	69	69
STAT5A (dimer)	-0.3	0.48	-10000	0	-1.1	74	74
STAT1	0.01	0.055	-10000	0	-0.51	4	4
SOCS3	-0.047	0.18	-10000	0	-0.58	38	38
CXCL9	-0.33	0.46	-10000	0	-1.1	70	70
MPO	-0.27	0.43	-10000	0	-1	65	65
positive regulation of humoral immune response	-0.32	0.5	-10000	0	-1.1	74	74
IL23/IL23R/JAK2/TYK2	-0.34	0.54	-10000	0	-1.2	74	74
IL6	-0.62	0.68	-10000	0	-1.3	174	174
STAT5A	0.014	0.031	-10000	0	-0.58	1	1
IL2	0.005	0.013	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0.003	0.008	-10000	0	-10000	0	0
CD3E	-0.33	0.53	-10000	0	-1.2	73	73
keratinocyte proliferation	-0.32	0.5	-10000	0	-1.1	74	74
NOS2	-0.3	0.46	-10000	0	-1	70	70

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.046	0.14	-9999	-0.36	58	58
EFNA5	-0.003	0.1	-9999	-0.58	11	11
FYN	-0.034	0.13	-9999	-0.32	61	61
neuron projection morphogenesis	-0.046	0.14	-9999	-0.36	58	58
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.046	0.14	-9999	-0.36	58	58
EPHA5	-0.072	0.2	-9999	-0.57	49	49

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.2	0.44	-9999	-0.94	53	53
HDAC7	0.018	0.002	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.13	0.36	-9999	-0.78	46	46
SMAD4	0.017	0	-9999	-10000	0	0
ID2	-0.2	0.44	-9999	-0.94	58	58
AP1	-0.12	0.23	-9999	-0.45	111	111
ABCG2	-0.21	0.45	-9999	-0.96	56	56
HIF1A	-0.015	0.083	-9999	-0.65	1	1
TFF3	-0.28	0.5	-9999	-1	80	80
GATA2	-0.005	0.11	-9999	-0.53	15	15
AKT1	-0.015	0.091	-9999	-10000	0	0
response to hypoxia	-0.039	0.096	-9999	-0.23	15	15
MCL1	-0.2	0.44	-9999	-0.93	56	56
NDRG1	-0.2	0.44	-9999	-0.95	54	54
SERPINE1	-0.2	0.45	-9999	-0.96	54	54
FECH	-0.2	0.44	-9999	-0.94	54	54
FURIN	-0.2	0.44	-9999	-0.93	56	56
NCOA2	-0.022	0.14	-9999	-0.57	23	23
EP300	-0.007	0.14	-9999	-0.33	23	23
HMOX1	-0.2	0.44	-9999	-0.93	56	56
BHLHE40	-0.2	0.44	-9999	-0.94	57	57
BHLHE41	-0.2	0.45	-9999	-0.96	56	56
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.001	0.081	-9999	-0.41	1	1
ENG	0.033	0.098	-9999	-10000	0	0
JUN	-0.005	0.11	-9999	-0.57	13	13
RORA	-0.2	0.45	-9999	-0.94	57	57
ABCB1	-0.19	0.39	-9999	-1.2	44	44
TFRC	-0.2	0.45	-9999	-0.94	57	57
CXCR4	-0.2	0.45	-9999	-0.96	54	54
TF	-0.23	0.46	-9999	-0.95	67	67
CITED2	-0.2	0.44	-9999	-0.94	54	54
HIF1A/ARNT	-0.2	0.52	-9999	-1	67	67
LDHA	-0.024	0.044	-9999	-10000	0	0
ETS1	-0.2	0.44	-9999	-0.94	54	54
PGK1	-0.2	0.44	-9999	-0.93	56	56
NOS2	-0.22	0.46	-9999	-0.98	61	61
ITGB2	-0.21	0.45	-9999	-0.95	58	58
ALDOA	-0.2	0.44	-9999	-0.94	53	53
Cbp/p300/CITED2	-0.18	0.46	-9999	-1	48	48
FOS	-0.17	0.27	-9999	-0.57	110	110
HK2	-0.2	0.44	-9999	-0.94	56	56
SP1	0.017	0.029	-9999	-10000	0	0
GCK	-0.086	0.4	-9999	-1.5	24	24
HK1	-0.2	0.44	-9999	-0.94	54	54
NPM1	-0.2	0.44	-9999	-0.93	56	56
EGLN1	-0.2	0.44	-9999	-0.94	53	53
CREB1	0.025	0	-9999	-10000	0	0
PGM1	-0.2	0.44	-9999	-0.94	54	54
SMAD3	0.017	0	-9999	-10000	0	0
EDN1	-0.054	0.22	-9999	-0.76	10	10
IGFBP1	-0.22	0.45	-9999	-0.94	62	62
VEGFA	-0.086	0.34	-9999	-0.74	26	26
HIF1A/JAB1	-0.007	0.043	-9999	-0.48	1	1
CP	-0.29	0.5	-9999	-0.99	85	85
CXCL12	-0.28	0.52	-9999	-1	88	88
COPS5	0.016	0.005	-9999	-10000	0	0
SMAD3/SMAD4	0.025	0.005	-9999	-10000	0	0
BNIP3	-0.2	0.44	-9999	-0.93	56	56
EGLN3	-0.2	0.44	-9999	-0.94	56	56
CA9	-0.36	0.5	-9999	-1	85	85
TERT	-0.29	0.48	-9999	-1	74	74
ENO1	-0.2	0.44	-9999	-0.93	56	56
PFKL	-0.2	0.44	-9999	-0.93	55	55
NCOA1	0.016	0.002	-9999	-10000	0	0
ADM	-0.2	0.44	-9999	-0.94	56	56
ARNT	-0.013	0.076	-9999	-10000	0	0
HNF4A	-0.04	0.16	-9999	-0.51	35	35
ADFP	-0.21	0.44	-9999	-0.89	67	67
SLC2A1	-0.089	0.34	-9999	-0.77	26	26
LEP	-0.24	0.47	-9999	-0.97	69	69
HIF1A/ARNT/Cbp/p300	-0.14	0.38	-9999	-0.8	48	48
EPO	-0.097	0.3	-9999	-0.8	11	11
CREBBP	-0.007	0.14	-9999	-0.34	22	22
HIF1A/ARNT/Cbp/p300/HDAC7	-0.12	0.37	-9999	-0.79	43	43
PFKFB3	-0.2	0.44	-9999	-0.95	53	53
NT5E	-0.22	0.48	-9999	-0.97	67	67

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.025	0.13	-10000	0	-0.3	65	65
ER alpha/Gai/GDP/Gbeta gamma	-0.18	0.34	-10000	0	-0.66	93	93
AKT1	-0.13	0.35	-10000	0	-0.9	61	61
PIK3CA	0.016	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.14	0.36	-10000	0	-0.93	61	61
mol:Ca2+	-0.04	0.18	-10000	0	-0.43	53	53
IGF1R	0.011	0.054	-10000	0	-0.58	3	3
E2/ER alpha (dimer)/Striatin	-0.043	0.14	-10000	0	-0.35	61	61
SHC1	0.014	0.028	-10000	0	-0.51	1	1
apoptosis	0.12	0.33	0.85	61	-10000	0	61
RhoA/GTP	-0.042	0.093	-10000	0	-0.48	1	1
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.17	0.25	-10000	0	-0.54	93	93
regulation of stress fiber formation	-0.011	0.1	0.4	4	-10000	0	4
E2/ERA-ERB (dimer)	-0.045	0.14	-10000	0	-0.35	63	63
KRAS	0.014	0.028	-10000	0	-0.51	1	1
G13/GTP	-0.038	0.13	-10000	0	-0.32	61	61
pseudopodium formation	0.011	0.1	-10000	0	-0.4	4	4
E2/ER alpha (dimer)/PELP1	-0.043	0.14	-10000	0	-0.35	61	61
GRB2	0.016	0	-10000	0	-10000	0	0
GNG2	0.006	0.076	-10000	0	-0.58	6	6
GNAO1	-0.17	0.27	-10000	0	-0.58	110	110
HRAS	0.016	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.12	0.29	-10000	0	-0.69	62	62
E2/ER beta (dimer)	0.009	0.028	-10000	0	-0.37	2	2
mol:GDP	-0.069	0.15	-10000	0	-0.4	61	61
mol:NADP	-0.12	0.29	-10000	0	-0.69	62	62
PIK3R1	0.016	0	-10000	0	-10000	0	0
mol:IP3	-0.043	0.19	-10000	0	-0.45	53	53
IGF-1R heterotetramer	0.011	0.054	-10000	0	-0.57	3	3
PLCB1	-0.051	0.19	-10000	0	-0.46	53	53
PLCB2	-0.044	0.18	-10000	0	-0.45	52	52
IGF1	-0.25	0.29	-10000	0	-0.58	159	159
mol:L-citrulline	-0.12	0.29	-10000	0	-0.69	62	62
RHOA	0.016	0	-10000	0	-10000	0	0
Gai/GDP	-0.25	0.41	-10000	0	-0.84	110	110
JNK cascade	0.009	0.028	-10000	0	-0.36	2	2
BCAR1	0.016	0	-10000	0	-10000	0	0
ESR2	0.013	0.039	-10000	0	-0.51	2	2
GNAQ	0.016	0	-10000	0	-10000	0	0
ESR1	-0.086	0.22	-10000	0	-0.58	61	61
Gq family/GDP/Gbeta gamma	-0.001	0.11	-10000	0	-0.51	4	4
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.026	0.12	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.17	0.25	-10000	0	-0.54	94	94
GNAZ	-0.11	0.24	-10000	0	-0.58	76	76
E2/ER alpha (dimer)	-0.063	0.16	-10000	0	-0.42	61	61
STRN	0.016	0	-10000	0	-10000	0	0
GNAL	-0.24	0.29	-10000	0	-0.58	154	154
PELP1	0.016	0	-10000	0	-10000	0	0
MAPK11	0.02	0.024	-10000	0	-0.3	2	2
GNAI2	0.016	0	-10000	0	-10000	0	0
GNAI3	0.016	0	-10000	0	-10000	0	0
GNAI1	0.011	0.054	-10000	0	-0.58	3	3
HBEGF	-0.19	0.29	-10000	0	-0.6	98	98
cAMP biosynthetic process	-0.17	0.19	-10000	0	-0.34	180	180
SRC	-0.16	0.32	-10000	0	-0.62	93	93
PI3K	0.023	0	-10000	0	-10000	0	0
GNB1	0.016	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.062	0.13	-10000	0	-0.35	61	61
SOS1	0.016	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.22	0.24	-10000	0	-0.5	132	132
Gs family/GTP	-0.17	0.19	-10000	0	-0.34	180	180
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.029	0.016	-10000	0	-0.26	1	1
vasodilation	-0.11	0.27	-10000	0	-0.65	62	62
mol:DAG	-0.043	0.19	-10000	0	-0.45	53	53
Gs family/GDP/Gbeta gamma	-0.15	0.18	-10000	0	-0.46	64	64
MSN	0.01	0.11	-10000	0	-0.43	4	4
Gq family/GTP	-0.054	0.19	-10000	0	-0.47	52	52
mol:PI-3-4-5-P3	-0.13	0.34	-10000	0	-0.88	61	61
NRAS	0.016	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.11	0.27	0.65	62	-10000	0	62
GRB2/SOS1	0.023	0	-10000	0	-10000	0	0
RhoA/GDP	-0.064	0.14	-10000	0	-0.37	61	61
NOS3	-0.13	0.31	-10000	0	-0.74	62	62
GNA11	0.014	0.031	-10000	0	-0.58	1	1
MAPKKK cascade	-0.11	0.29	-10000	0	-0.7	61	61
E2/ER alpha (dimer)/PELP1/Src	-0.18	0.27	-10000	0	-0.58	93	93
ruffle organization	0.011	0.1	-10000	0	-0.4	4	4
ROCK2	0.002	0.11	-10000	0	-0.47	3	3
GNA14	-0.067	0.2	-10000	0	-0.58	50	50
GNA15	0.012	0.044	-10000	0	-0.58	2	2
GNA13	0.016	0	-10000	0	-10000	0	0
MMP9	-0.21	0.29	-10000	0	-0.62	93	93
MMP2	-0.17	0.31	-10000	0	-0.59	102	102

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.13	0.23	-9999	-0.41	116	116
MAP3K8	0.007	0.054	-9999	-0.58	3	3
FOS	-0.092	0.18	-9999	-0.45	46	46
PRKCA	0.007	0.054	-9999	-0.58	3	3
PTPN7	-0.003	0.095	-9999	-0.56	10	10
HRAS	0.015	0.002	-9999	-10000	0	0
PRKCB	-0.16	0.27	-9999	-0.58	103	103
NRAS	0.015	0.002	-9999	-10000	0	0
RAS family/GTP	0.022	0.022	-9999	-0.28	1	1
MAPK3	-0.048	0.12	-9999	-0.51	9	9
MAP2K1	-0.11	0.23	-9999	-0.46	103	103
ELK1	0.01	0.01	-9999	-10000	0	0
BRAF	-0.11	0.22	-9999	-0.44	103	103
mol:GTP	-0.001	0.003	-9999	-0.005	109	109
MAPK1	-0.048	0.12	-9999	-0.46	11	11
RAF1	-0.11	0.22	-9999	-0.44	103	103
KRAS	0.013	0.028	-9999	-0.51	1	1

×

Integrins in angiogenesis

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.022	0.023	-9999	-0.41	1	1
alphaV beta3 Integrin	-0.13	0.24	-9999	-0.43	126	126
PTK2	-0.11	0.24	-9999	-0.55	62	62
IGF1R	0.011	0.054	-9999	-0.58	3	3
PI4KB	0.016	0	-9999	-10000	0	0
MFGE8	0.012	0.044	-9999	-0.58	2	2
SRC	0.016	0	-9999	-10000	0	0
CDKN1B	-0.14	0.29	-9999	-0.72	62	62
VEGFA	0.016	0	-9999	-10000	0	0
ILK	-0.14	0.29	-9999	-0.72	62	62
ROCK1	0.016	0	-9999	-10000	0	0
AKT1	-0.12	0.27	-9999	-0.67	62	62
PTK2B	0.005	0.11	-9999	-0.29	43	43
alphaV/beta3 Integrin/JAM-A	-0.15	0.27	-9999	-0.65	62	62
CBL	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.021	0.13	-9999	-0.36	46	46
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.12	0.18	-9999	-0.32	163	163
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.022	0.14	-9999	-0.43	18	18
alphaV/beta3 Integrin/Syndecan-1	-0.019	0.13	-9999	-0.35	47	47
PI4KA	0.016	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.26	0.29	-9999	-0.63	115	115
PI4 Kinase	0.023	0	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.14	0.18	-9999	-0.31	179	179
RPS6KB1	-0.21	0.29	-9999	-0.58	115	115
TLN1	0.016	0	-9999	-10000	0	0
MAPK3	-0.28	0.41	-9999	-0.79	126	126
GPR124	-0.049	0.18	-9999	-0.58	39	39
MAPK1	-0.28	0.41	-9999	-0.79	126	126
PXN	0.016	0	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.12	0.21	-9999	-0.39	132	132
cell adhesion	-0.035	0.12	-9999	-0.34	43	43
ANGPTL3	0.004	0.061	-9999	-0.51	5	5
VEGFR2 homodimer/VEGFA homodimer/Src	0.031	0.02	-9999	-0.34	1	1
IGF-1R heterotetramer	0.011	0.054	-9999	-0.57	3	3
Rac1/GDP	0.012	0	-9999	-10000	0	0
TGFBR2	0.012	0.044	-9999	-0.58	2	2
ITGB3	-0.054	0.19	-9999	-0.58	42	42
IGF1	-0.25	0.29	-9999	-0.58	159	159
RAC1	0.016	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.052	0.19	-9999	-0.45	61	61
apoptosis	0.014	0.031	-9999	-0.57	1	1
CD47	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.013	0.12	-9999	-0.35	42	42
VCL	0.014	0.031	-9999	-0.58	1	1
alphaV/beta3 Integrin/Del1	-0.062	0.2	-9999	-0.45	70	70
CSF1	-0.006	0.11	-9999	-0.58	13	13
PIK3C2A	-0.14	0.29	-9999	-0.72	62	62
PI4 Kinase/Pyk2	-0.15	0.21	-9999	-0.55	62	62
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.002	0.12	-9999	-0.32	42	42
FAK1/Vinculin	-0.078	0.19	-9999	-0.42	63	63
alphaV beta3/Integrin/ppsTEM5	-0.052	0.2	-9999	-0.46	61	61
RHOA	0.016	0	-9999	-10000	0	0
VTN	-0.093	0.23	-9999	-0.57	66	66
BCAR1	0.016	0	-9999	-10000	0	0
FGF2	-0.18	0.28	-9999	-0.58	116	116
F11R	-0.12	0.21	-9999	-0.42	116	116
alphaV/beta3 Integrin/Lactadherin	-0.015	0.13	-9999	-0.36	43	43
alphaV/beta3 Integrin/TGFBR2	-0.015	0.13	-9999	-0.36	43	43
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.027	0.067	-9999	-0.3	14	14
HSP90AA1	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.011	0.11	-9999	-0.32	42	42
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.035	0.16	-9999	-0.53	33	33
alphaV/beta3 Integrin/Pyk2	0.006	0.11	-9999	-0.29	43	43
SDC1	0.007	0.07	-9999	-0.58	5	5
VAV3	0.026	0.075	-9999	-10000	0	0
PTPN11	0.016	0	-9999	-10000	0	0
IRS1	0.004	0.082	-9999	-0.58	7	7
FAK1/Paxillin	-0.077	0.19	-9999	-0.42	62	62
cell migration	-0.061	0.17	-9999	-0.4	47	47
ITGAV	0.014	0.031	-9999	-0.58	1	1
PI3K	-0.16	0.22	-9999	-0.58	62	62
SPP1	-0.19	0.26	-9999	-0.51	141	141
KDR	0.014	0.031	-9999	-0.58	1	1
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.014	0.031	-9999	-0.57	1	1
COL4A3	-0.16	0.27	-9999	-0.57	107	107
angiogenesis	-0.27	0.4	-9999	-0.77	127	127
Rac1/GTP	0.032	0.069	-9999	-10000	0	0
EDIL3	-0.066	0.2	-9999	-0.58	49	49
cell proliferation	-0.015	0.13	-9999	-0.36	43	43

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.12	0.17	-10000	0	-0.3	156	156
MAPK9	0.01	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.1	0.17	-10000	0	-0.37	102	102
GNB1/GNG2	0.015	0.048	-10000	0	-0.35	6	6
GNB1	0.016	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.01	0	-10000	0	-10000	0	0
Gs family/GTP	-0.14	0.17	-10000	0	-0.33	154	154
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	0.037	0.042	0.085	154	-10000	0	154
GNAL	-0.24	0.29	-10000	0	-0.58	154	154
GNG2	0.006	0.076	-10000	0	-0.58	6	6
CRH	-0.14	0.24	-10000	0	-0.51	102	102
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.007	0.034	-10000	0	-0.36	3	3
MAPK11	0.01	0	-10000	0	-10000	0	0

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.13	0.21	-9999	-0.35	143	143
SMAD6-7/SMURF1	0.027	0.041	-9999	-0.31	5	5
NOG	-0.028	0.14	-9999	-0.51	28	28
SMAD9	-0.15	0.25	-9999	-0.54	95	95
SMAD4	0.016	0	-9999	-10000	0	0
SMAD5	-0.035	0.11	-9999	-0.31	16	16
BMP7/USAG1	-0.27	0.27	-9999	-0.49	203	203
SMAD5/SKI	-0.025	0.1	-9999	-0.37	5	5
SMAD1	0.046	0.022	-9999	-10000	0	0
BMP2	-0.047	0.18	-9999	-0.58	38	38
SMAD1/SMAD1/SMAD4	-0.002	0.02	-9999	-10000	0	0
BMPR1A	0.016	0	-9999	-10000	0	0
BMPR1B	-0.066	0.19	-9999	-0.51	54	54
BMPR1A-1B/BAMBI	-0.051	0.16	-9999	-0.35	77	77
AHSG	-0.061	0.17	-9999	-0.51	46	46
CER1	0.004	0.007	-9999	-10000	0	0
BMP2-4/CER1	-0.034	0.14	-9999	-0.35	56	56
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.067	0.15	-9999	-0.36	35	35
BMP2-4 (homodimer)	-0.045	0.16	-9999	-0.41	56	56
RGMB	0.016	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.008	0.11	-9999	-0.3	6	6
RGMA	-0.16	0.27	-9999	-0.58	105	105
SMURF1	0.016	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.069	0.14	-9999	-0.36	37	37
BMP2-4/USAG1	-0.15	0.22	-9999	-0.39	156	156
SMAD6/SMURF1/SMAD5	-0.025	0.1	-9999	-0.37	5	5
SOSTDC1	-0.19	0.28	-9999	-0.57	122	122
BMP7/BMPR2/BMPR1A-1B	-0.12	0.2	-9999	-0.34	154	154
SKI	0.016	0	-9999	-10000	0	0
BMP6 (homodimer)	0.011	0.05	-9999	-0.53	3	3
HFE2	0.002	0.048	-9999	-0.51	3	3
ZFYVE16	0.016	0	-9999	-10000	0	0
MAP3K7	0.016	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.063	0.18	-9999	-0.38	83	83
SMAD5/SMAD5/SMAD4	-0.025	0.1	-9999	-0.37	5	5
MAPK1	0.016	0	-9999	-10000	0	0
TAK1/TAB family	-0.072	0.096	-9999	-0.35	21	21
BMP7 (homodimer)	-0.19	0.28	-9999	-0.57	123	123
NUP214	0.016	0	-9999	-10000	0	0
BMP6/FETUA	-0.036	0.13	-9999	-0.36	49	49
SMAD1/SKI	0.053	0.02	-9999	-10000	0	0
SMAD6	0.01	0.057	-9999	-0.52	4	4
CTDSP2	0.016	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.073	0.17	-9999	-0.35	93	93
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.15	0.26	-9999	-0.54	108	108
BMPR2 (homodimer)	0.016	0	-9999	-10000	0	0
GADD34/PP1CA	0.032	0	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.036	0.14	-9999	-0.36	54	54
CHRDL1	-0.33	0.29	-9999	-0.58	208	208
ENDOFIN/SMAD1	0.053	0.02	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	0.001	0.026	-9999	-10000	0	0
SMAD6/SMURF1	0.016	0	-9999	-10000	0	0
BAMBI	-0.038	0.17	-9999	-0.56	33	33
SMURF2	0.016	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.24	0.22	-9999	-0.39	231	231
BMP2-4/GREM1	-0.13	0.19	-9999	-0.34	159	159
SMAD7	0.014	0.031	-9999	-0.58	1	1
SMAD8A/SMAD8A/SMAD4	-0.14	0.24	-9999	-0.51	95	95
SMAD1/SMAD6	0.053	0.02	-9999	-10000	0	0
TAK1/SMAD6	0.023	0	-9999	-10000	0	0
BMP7	-0.19	0.28	-9999	-0.58	123	123
BMP6	0.011	0.05	-9999	-0.53	3	3
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.06	0.13	-9999	-0.33	37	37
PPM1A	0.016	0	-9999	-10000	0	0
SMAD1/SMURF2	0.053	0.02	-9999	-10000	0	0
SMAD7/SMURF1	0.022	0.023	-9999	-0.41	1	1
CTDSPL	0.016	0	-9999	-10000	0	0
PPP1CA	0.016	0	-9999	-10000	0	0
XIAP	0.012	0.042	-9999	-0.54	2	2
CTDSP1	0.016	0	-9999	-10000	0	0
PPP1R15A	0.016	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.097	0.17	-9999	-0.44	46	46
CHRD	-0.044	0.18	-9999	-0.57	36	36
BMPR2	0.016	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.084	0.15	-9999	-0.4	36	36
BMP4	-0.014	0.13	-9999	-0.56	18	18
FST	-0.028	0.15	-9999	-0.56	27	27
BMP2-4/NOG	-0.052	0.17	-9999	-0.38	72	72
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.11	0.19	-9999	-0.32	128	128

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.17	0.28	-10000	0	-0.5	136	136
fibroblast growth factor receptor signaling pathway	-0.17	0.28	-10000	0	-0.5	136	136
LAMA1	-0.087	0.21	-10000	0	-0.52	68	68
PRNP	0.002	0.088	-10000	0	-0.58	8	8
GPC1/SLIT2	-0.18	0.22	-10000	0	-0.42	168	168
SMAD2	0.036	0.03	-10000	0	-0.3	2	2
GPC1/PrPc/Cu2+	0.012	0.058	-10000	0	-0.35	9	9
GPC1/Laminin alpha1	-0.052	0.16	-10000	0	-0.37	68	68
TDGF1	0.007	0.028	-10000	0	-0.51	1	1
CRIPTO/GPC1	0.016	0.029	-10000	0	-0.36	2	2
APP/GPC1	0.02	0.038	-10000	0	-0.39	3	3
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0.026	0.025	-10000	0	-0.3	2	2
FLT1	0.016	0	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	0.029	0.033	-10000	0	-0.33	3	3
SERPINC1	-0.031	0.14	-10000	0	-0.51	30	30
FYN	0.023	0.042	-10000	0	-0.33	5	5
FGR	0.025	0.031	-10000	0	-0.31	3	3
positive regulation of MAPKKK cascade	0.023	0.075	-10000	0	-0.36	3	3
SLIT2	-0.26	0.3	-10000	0	-0.58	168	168
GPC1/NRG	-0.074	0.18	-10000	0	-0.4	81	81
NRG1	-0.11	0.24	-10000	0	-0.56	80	80
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.031	0.017	-10000	0	-0.29	1	1
LYN	0.026	0.025	-10000	0	-0.3	2	2
mol:Spermine	0.012	0.02	-10000	0	-0.37	1	1
cell growth	-0.17	0.28	-10000	0	-0.5	136	136
BMP signaling pathway	-0.014	0.028	0.51	1	-10000	0	1
SRC	0.026	0.025	-10000	0	-0.3	2	2
TGFBR1	0.016	0	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.26	0.29	-10000	0	-0.57	165	165
GPC1	0.014	0.028	-10000	0	-0.51	1	1
TGFBR1 (dimer)	0.016	0	-10000	0	-10000	0	0
VEGFA	0.016	0	-10000	0	-10000	0	0
BLK	-0.019	0.12	-10000	0	-0.33	44	44
HCK	0.009	0.081	-10000	0	-0.33	19	19
FGF2	-0.18	0.28	-10000	0	-0.58	116	116
FGFR1	-0.12	0.25	-10000	0	-0.58	83	83
VEGFR1 homodimer	0.016	0	-10000	0	-10000	0	0
TGFBR2	0.012	0.044	-10000	0	-0.58	2	2
cell death	0.02	0.038	-10000	0	-0.39	3	3
ATIII/GPC1	-0.012	0.11	-10000	0	-0.36	31	31
PLA2G2A/GPC1	-0.18	0.22	-10000	0	-0.41	165	165
LCK	0.02	0.052	-10000	0	-0.32	8	8
neuron differentiation	-0.073	0.18	-10000	0	-0.4	81	81
PrPc/Cu2+	0.002	0.064	-10000	0	-0.42	8	8
APP	0.012	0.044	-10000	0	-0.58	2	2
TGFBR2 (dimer)	0.012	0.044	-10000	0	-0.57	2	2

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.08	0.18	-9999	-0.46	53	53
alphaM/beta2 Integrin/GPIbA	-0.055	0.13	-9999	-0.42	35	35
alphaM/beta2 Integrin/proMMP-9	-0.13	0.19	-9999	-0.38	112	112
PLAUR	0.016	0	-9999	-10000	0	0
HMGB1	-0.003	0.023	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.049	0.12	-9999	-0.44	29	29
AGER	-0.012	0.073	-9999	-0.54	6	6
RAP1A	0.016	0	-9999	-10000	0	0
SELPLG	0.001	0.09	-9999	-0.56	9	9
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.11	0.14	-9999	-0.51	26	26
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.13	0.24	-9999	-0.51	97	97
CYR61	-0.16	0.27	-9999	-0.58	106	106
TLN1	0.016	0	-9999	-10000	0	0
Rap1/GTP	-0.061	0.14	-9999	-0.51	21	21
RHOA	0.016	0	-9999	-10000	0	0
P-selectin oligomer	-0.11	0.24	-9999	-0.57	75	75
MYH2	-0.056	0.15	-9999	-0.44	26	26
MST1R	-0.016	0.13	-9999	-0.55	20	20
leukocyte activation during inflammatory response	-0.12	0.18	-9999	-0.37	102	102
APOB	-0.083	0.21	-9999	-0.57	58	58
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.037	0.17	-9999	-0.58	32	32
JAM3	-0.023	0.14	-9999	-0.58	23	23
GP1BA	0.004	0.074	-9999	-0.52	7	7
alphaM/beta2 Integrin/CTGF	-0.12	0.21	-9999	-0.46	88	88
alphaM/beta2 Integrin	-0.059	0.17	-9999	-0.55	25	25
JAM3 homodimer	-0.023	0.14	-9999	-0.57	23	23
ICAM2	0.014	0.031	-9999	-0.58	1	1
ICAM1	0.005	0.074	-9999	-0.52	7	7
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.058	0.17	-9999	-0.54	25	25
cell adhesion	-0.055	0.13	-9999	-0.42	35	35
NFKB1	-0.14	0.22	-9999	-0.62	24	24
THY1	0.013	0.039	-9999	-0.51	2	2
RhoA/GDP	0.012	0	-9999	-10000	0	0
Lipoprotein(a)	-0.079	0.17	-9999	-0.37	86	86
alphaM/beta2 Integrin/LRP/tPA	-0.036	0.16	-9999	-0.46	36	36
IL6	-0.34	0.42	-9999	-0.77	167	167
ITGB2	-0.029	0.12	-9999	-0.56	16	16
elevation of cytosolic calcium ion concentration	-0.074	0.14	-9999	-0.37	44	44
alphaM/beta2 Integrin/JAM2/JAM3	-0.13	0.24	-9999	-0.44	112	112
JAM2	-0.14	0.26	-9999	-0.58	96	96
alphaM/beta2 Integrin/ICAM1	-0.066	0.15	-9999	-0.42	37	37
alphaM/beta2 Integrin/uPA/Plg	-0.079	0.15	-9999	-0.33	78	78
RhoA/GTP	-0.049	0.15	-9999	-0.47	24	24
positive regulation of phagocytosis	-0.071	0.17	-9999	-0.53	31	31
Ron/MSP	-0.021	0.13	-9999	-0.39	38	38
alphaM/beta2 Integrin/uPAR/uPA	-0.057	0.15	-9999	-0.37	44	44
alphaM/beta2 Integrin/uPAR	-0.049	0.12	-9999	-0.44	29	29
PLAU	-0.055	0.18	-9999	-0.51	48	48
PLAT	-0.014	0.13	-9999	-0.57	18	18
actin filament polymerization	-0.053	0.14	-9999	-0.42	26	26
MST1	-0.014	0.12	-9999	-0.51	20	20
alphaM/beta2 Integrin/lipoprotein(a)	-0.12	0.18	-9999	-0.37	102	102
TNF	-0.13	0.21	-9999	-0.56	24	24
RAP1B	0.016	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.089	0.15	-9999	-0.36	76	76
fibrinolysis	-0.082	0.14	-9999	-0.34	73	73
HCK	-0.012	0.12	-9999	-0.56	17	17
dendritic cell antigen processing and presentation	-0.058	0.17	-9999	-0.54	25	25
VTN	-0.093	0.23	-9999	-0.57	66	66
alphaM/beta2 Integrin/CYR61	-0.15	0.23	-9999	-0.46	114	114
LPA	-0.046	0.17	-9999	-0.56	35	35
LRP1	0.011	0.054	-9999	-0.58	3	3
cell migration	-0.13	0.22	-9999	-0.44	76	76
FN1	-0.035	0.16	-9999	-0.53	33	33
alphaM/beta2 Integrin/Thy1	-0.05	0.12	-9999	-0.43	31	31
MPO	0.01	0.039	-9999	-0.51	2	2
KNG1	0	0	-9999	-10000	0	0
RAP1/GDP	0.021	0	-9999	-10000	0	0
ROCK1	-0.038	0.14	-9999	-0.46	20	20
ELA2	0	0	-9999	-10000	0	0
PLG	-0.003	0.06	-9999	-0.51	5	5
CTGF	-0.1	0.24	-9999	-0.58	73	73
alphaM/beta2 Integrin/Hck	-0.064	0.17	-9999	-0.52	35	35
ITGAM	-0.037	0.14	-9999	-0.59	20	20
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.096	0.21	-9999	-0.4	92	92
HP	-0.055	0.18	-9999	-0.51	46	46
leukocyte adhesion	-0.17	0.22	-9999	-0.5	89	89
SELP	-0.11	0.24	-9999	-0.58	75	75

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.011	0.086	-9999	-0.38	17	17
NFATC2	-0.061	0.15	-9999	-0.38	62	62
NFATC3	0.007	0.028	-9999	-10000	0	0
CD40LG	-0.26	0.33	-9999	-0.73	89	89
PTGS2	-0.3	0.36	-9999	-0.7	129	129
JUNB	0.009	0.062	-9999	-0.58	4	4
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.005	0.011	-9999	-10000	0	0
CaM/Ca2+	-0.005	0.011	-9999	-10000	0	0
CALM1	0.012	0.008	-9999	-10000	0	0
JUN	-0.01	0.11	-9999	-0.58	13	13
mol:Ca2+	-0.009	0.011	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.003	0.004	-9999	-10000	0	0
FOSL1	-0.024	0.15	-9999	-0.58	24	24
CREM	0.015	0	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.13	0.18	-9999	-0.49	51	51
FOS	-0.17	0.28	-9999	-0.59	110	110
IFNG	-0.28	0.33	-9999	-0.71	95	95
AP-1/NFAT1-c-4	-0.29	0.38	-9999	-0.71	121	121
FASLG	-0.25	0.32	-9999	-0.71	85	85
NFAT1-c-4/ICER1	-0.075	0.16	-9999	-0.4	52	52
IL2RA	-0.25	0.33	-9999	-0.76	76	76
FKBP12/FK506	0.012	0	-9999	-10000	0	0
CSF2	-0.27	0.33	-9999	-0.67	108	108
JunB/Fra1/NFAT1-c-4	-0.1	0.17	-9999	-0.42	59	59
IL4	-0.24	0.3	-9999	-0.67	78	78
IL2	-0.009	0.019	-9999	-10000	0	0
IL3	-0.024	0.023	-9999	-10000	0	0
FKBP1A	0.016	0	-9999	-10000	0	0
BATF3	0.003	0.084	-9999	-0.55	8	8
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.016	0.002	-9999	-10000	0	0

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.064	0.24	-10000	0	-0.64	26	26
CRP	-0.075	0.25	-10000	0	-0.68	26	26
cell cycle arrest	-0.075	0.27	-10000	0	-0.65	46	46
TIMP1	-0.056	0.22	-10000	0	-0.5	38	38
IL6ST	-0.073	0.22	-10000	0	-0.58	56	56
Rac1/GDP	-0.14	0.27	-10000	0	-0.57	74	74
AP1	-0.056	0.18	-10000	0	-0.45	23	23
GAB2	0.019	0.007	-10000	0	-10000	0	0
TNFSF11	-0.076	0.26	-10000	0	-0.67	32	32
HSP90B1	0.022	0.056	-10000	0	-0.56	1	1
GAB1	0.018	0.004	-10000	0	-10000	0	0
MAPK14	-0.17	0.31	-10000	0	-0.72	69	69
AKT1	0.064	0.015	-10000	0	-10000	0	0
FOXO1	0.07	0.013	-10000	0	-10000	0	0
MAP2K6	-0.17	0.29	-10000	0	-0.62	76	76
mol:GTP	0	0.001	-10000	0	-10000	0	0
MAP2K4	-0.1	0.26	-10000	0	-0.6	56	56
MITF	-0.17	0.29	-10000	0	-0.56	91	91
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.016	0	-10000	0	-10000	0	0
A2M	-0.096	0.41	-10000	0	-1.4	30	30
CEBPB	0.023	0.032	-10000	0	-0.57	1	1
GRB2/SOS1/GAB family/SHP2	-0.017	0.097	0.25	1	-10000	0	1
STAT3	-0.086	0.29	-10000	0	-0.7	46	46
STAT1	-0.007	0.019	-10000	0	-10000	0	0
CEBPD	-0.066	0.25	-10000	0	-0.69	23	23
PIK3CA	0.018	0	-10000	0	-10000	0	0
PI3K	0.026	0.001	-10000	0	-10000	0	0
JUN	-0.006	0.11	-10000	0	-0.58	13	13
PIAS3/MITF	-0.15	0.27	-10000	0	-0.55	84	84
MAPK11	-0.17	0.31	-10000	0	-0.72	69	69
STAT3 (dimer)/FOXO1	-0.035	0.24	-10000	0	-0.56	35	35
GRB2/SOS1/GAB family	-0.14	0.21	0.21	4	-0.58	51	55
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.17	0.28	-10000	0	-0.5	101	101
GRB2	0.018	0.004	-10000	0	-10000	0	0
JAK2	0.014	0.031	-10000	0	-0.58	1	1
LBP	-0.073	0.22	-10000	0	-0.57	21	21
PIK3R1	0.017	0	-10000	0	-10000	0	0
JAK1	0.017	0.007	-10000	0	-10000	0	0
MYC	-0.091	0.32	-10000	0	-0.92	31	31
FGG	-0.09	0.26	-10000	0	-0.66	34	34
macrophage differentiation	-0.075	0.27	-10000	0	-0.65	46	46
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.19	0.24	-10000	0	-0.53	78	78
JUNB	-0.067	0.25	-10000	0	-0.67	28	28
FOS	-0.17	0.27	-10000	0	-0.58	110	110
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.16	0.28	-10000	0	-0.52	96	96
STAT1/PIAS1	-0.12	0.24	-10000	0	-0.54	61	61
GRB2/SOS1/GAB family/SHP2/PI3K	0.051	0.018	-10000	0	-10000	0	0
STAT3 (dimer)	-0.082	0.28	-10000	0	-0.68	46	46
PRKCD	-0.076	0.26	-10000	0	-0.59	50	50
IL6R	-0.034	0.17	-10000	0	-0.57	31	31
SOCS3	-0.22	0.42	-10000	0	-1.1	58	58
gp130 (dimer)/JAK1/JAK1/LMO4	-0.018	0.14	-10000	0	-0.34	57	57
Rac1/GTP	-0.13	0.27	-10000	0	-0.58	69	69
HCK	-0.011	0.12	-10000	0	-0.56	17	17
MAPKKK cascade	0.022	0.075	-10000	0	-10000	0	0
bone resorption	-0.071	0.25	-10000	0	-0.63	33	33
IRF1	-0.064	0.24	-10000	0	-0.66	23	23
mol:GDP	-0.15	0.28	-10000	0	-0.58	79	79
SOS1	0.018	0.007	-10000	0	-10000	0	0
VAV1	-0.16	0.28	-10000	0	-0.6	79	79
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.2	0.35	-10000	0	-0.78	72	72
PTPN11	-0.005	0.018	-10000	0	-10000	0	0
IL6/IL6RA	-0.2	0.26	-10000	0	-0.46	170	170
gp130 (dimer)/TYK2/TYK2/LMO4	-0.023	0.14	-10000	0	-0.34	57	57
gp130 (dimer)/JAK2/JAK2/LMO4	-0.024	0.14	-10000	0	-0.35	57	57
IL6	-0.25	0.3	-10000	0	-0.57	162	162
PIAS3	0.016	0	-10000	0	-10000	0	0
PTPRE	0.006	0.042	-10000	0	-0.52	2	2
PIAS1	0.016	0	-10000	0	-10000	0	0
RAC1	0.016	0.001	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.17	0.26	-10000	0	-0.37	175	175
LMO4	0.018	0.033	-10000	0	-0.58	1	1
STAT3 (dimer)/PIAS3	-0.15	0.24	-10000	0	-0.68	46	46
MCL1	0.07	0.014	-10000	0	-10000	0	0

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.016	0	-9999	-10000	0	0
CCL5	-0.03	0.16	-9999	-0.55	29	29
SDCBP	0.016	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.12	0.14	-9999	-0.35	50	50
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.11	0.13	-9999	-0.39	21	21
Syndecan-1/Syntenin	-0.11	0.13	-9999	-0.33	50	50
MAPK3	-0.082	0.12	-9999	-0.4	12	12
HGF/MET	-0.081	0.18	-9999	-0.41	86	86
TGFB1/TGF beta receptor Type II	0.016	0	-9999	-10000	0	0
BSG	0.016	0	-9999	-10000	0	0
keratinocyte migration	-0.1	0.13	-9999	-0.38	21	21
Syndecan-1/RANTES	-0.13	0.16	-9999	-0.39	62	62
Syndecan-1/CD147	-0.094	0.12	-9999	-0.42	13	13
Syndecan-1/Syntenin/PIP2	-0.1	0.12	-9999	-0.32	50	50
LAMA5	0.016	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.12	0.11	-9999	-0.31	50	50
MMP7	-0.11	0.23	-9999	-0.52	85	85
HGF	-0.12	0.25	-9999	-0.57	85	85
Syndecan-1/CASK	-0.12	0.13	-9999	-0.34	50	50
Syndecan-1/HGF/MET	-0.16	0.18	-9999	-0.45	71	71
regulation of cell adhesion	-0.072	0.12	-9999	-0.44	6	6
HPSE	-0.032	0.15	-9999	-0.51	32	32
positive regulation of cell migration	-0.12	0.14	-9999	-0.35	50	50
SDC1	-0.12	0.14	-9999	-0.36	50	50
Syndecan-1/Collagen	-0.12	0.14	-9999	-0.35	50	50
PPIB	0.016	0	-9999	-10000	0	0
MET	0.014	0.028	-9999	-0.51	1	1
PRKACA	0.016	0	-9999	-10000	0	0
MMP9	-0.13	0.24	-9999	-0.51	97	97
MAPK1	-0.082	0.12	-9999	-0.4	12	12
homophilic cell adhesion	-0.12	0.14	-9999	-0.35	50	50
MMP1	-0.28	0.26	-9999	-0.51	204	204

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.097	0.21	-10000	0	-0.55	57	57
FYN	-0.081	0.33	-10000	0	-0.74	62	62
LAT/GRAP2/SLP76	-0.11	0.25	-10000	0	-0.6	64	64
IKBKB	0.016	0	-10000	0	-10000	0	0
AKT1	-0.032	0.21	-10000	0	-0.46	59	59
B2M	0.015	0.005	-10000	0	-10000	0	0
IKBKG	-0.023	0.044	-10000	0	-0.14	22	22
MAP3K8	0.011	0.054	-10000	0	-0.58	3	3
mol:Ca2+	-0.023	0.038	-10000	0	-0.11	37	37
integrin-mediated signaling pathway	0.019	0.028	-10000	0	-0.35	2	2
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.072	0.31	-10000	0	-0.7	60	60
TRPV6	-0.11	0.22	-10000	0	-0.56	70	70
CD28	-0.011	0.12	-10000	0	-0.58	16	16
SHC1	-0.074	0.3	-10000	0	-0.69	62	62
receptor internalization	-0.085	0.32	-10000	0	-0.72	62	62
PRF1	-0.09	0.35	-10000	0	-0.94	41	41
KRAS	0.014	0.028	-10000	0	-0.51	1	1
GRB2	0.016	0	-10000	0	-10000	0	0
COT/AKT1	-0.014	0.17	-10000	0	-0.36	57	57
LAT	-0.074	0.3	-10000	0	-0.69	62	62
EntrezGene:6955	0	0.004	-10000	0	-10000	0	0
CD3D	-0.047	0.18	-10000	0	-0.58	38	38
CD3E	-0.051	0.19	-10000	0	-0.59	40	40
CD3G	-0.055	0.19	-10000	0	-0.58	42	42
RASGRP2	-0.041	0.083	-10000	0	-0.17	97	97
RASGRP1	-0.027	0.21	-10000	0	-0.46	58	58
HLA-A	0.013	0.032	-10000	0	-0.59	1	1
RASSF5	0.012	0.044	-10000	0	-0.58	2	2
RAP1A/GTP/RAPL	0.019	0.028	-10000	0	-0.35	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.005	0.07	-10000	0	-0.13	53	53
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.042	0.078	-10000	0	-0.22	44	44
PRKCA	-0.044	0.11	-10000	0	-0.28	56	56
GRAP2	-0.057	0.19	-10000	0	-0.58	44	44
mol:IP3	-0.05	0.21	0.23	58	-0.46	56	114
EntrezGene:6957	0	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.089	0.32	-10000	0	-0.72	59	59
ORAI1	0.063	0.12	0.31	70	-0.37	1	71
CSK	-0.077	0.31	-10000	0	-0.72	60	60
B7 family/CD28	-0.15	0.28	-10000	0	-0.66	66	66
CHUK	0.016	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.1	0.36	-10000	0	-0.82	62	62
PTPN6	-0.081	0.31	-10000	0	-0.7	62	62
VAV1	-0.083	0.32	-10000	0	-0.72	64	64
Monovalent TCR/CD3	-0.079	0.26	-10000	0	-0.55	69	69
CBL	0.016	0	-10000	0	-10000	0	0
LCK	-0.087	0.33	-10000	0	-0.75	62	62
PAG1	-0.077	0.31	-10000	0	-0.71	61	61
RAP1A	0.016	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.1	0.36	-10000	0	-0.8	64	64
CD80	-0.05	0.17	-10000	0	-0.51	44	44
CD86	0.009	0.061	-10000	0	-0.56	4	4
PDK1/CARD11/BCL10/MALT1	-0.051	0.095	-10000	0	-0.26	52	52
HRAS	0.016	0	-10000	0	-10000	0	0
GO:0035030	-0.069	0.25	-10000	0	-0.55	64	64
CD8A	-0.047	0.18	-10000	0	-0.58	38	38
CD8B	-0.042	0.18	-10000	0	-0.58	35	35
PTPRC	-0.059	0.2	-10000	0	-0.58	45	45
PDK1/PKC theta	-0.044	0.26	-10000	0	-0.57	61	61
CSK/PAG1	-0.068	0.3	-10000	0	-0.7	57	57
SOS1	0.016	0	-10000	0	-10000	0	0
peptide-MHC class I	0.02	0.026	-10000	0	-0.43	1	1
GRAP2/SLP76	-0.13	0.3	-10000	0	-0.71	65	65
STIM1	0.034	0.061	-10000	0	-10000	0	0
RAS family/GTP	0.021	0.089	-10000	0	-0.17	44	44
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.096	0.35	-10000	0	-0.79	62	62
mol:DAG	-0.064	0.16	-10000	0	-0.4	59	59
RAP1A/GDP	0.004	0.031	-10000	0	-0.064	2	2
PLCG1	0.016	0	-10000	0	-10000	0	0
CD247	0.004	0.082	-10000	0	-0.57	7	7
cytotoxic T cell degranulation	-0.083	0.33	-10000	0	-0.85	43	43
RAP1A/GTP	-0.018	0.027	-10000	0	-0.069	31	31
mol:PI-3-4-5-P3	-0.049	0.25	-10000	0	-0.56	60	60
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.074	0.26	0.25	53	-0.61	56	109
NRAS	0.016	0	-10000	0	-10000	0	0
ZAP70	-0.008	0.12	-10000	0	-0.58	14	14
GRB2/SOS1	0.023	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.1	0.24	-10000	0	-0.6	59	59
MALT1	0.016	0	-10000	0	-10000	0	0
TRAF6	0.016	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.061	0.22	-10000	0	-0.55	53	53
CARD11	0.001	0.09	-10000	0	-0.56	9	9
PRKCB	-0.09	0.16	-10000	0	-0.36	74	74
PRKCE	-0.043	0.11	-10000	0	-0.28	56	56
PRKCQ	-0.066	0.3	-10000	0	-0.67	61	61
LCP2	0.012	0.044	-10000	0	-0.58	2	2
BCL10	0.016	0	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.021	0.18	-10000	0	-0.39	59	59
IKK complex	0.014	0.071	-10000	0	-0.12	46	46
RAS family/GDP	-0.005	0.011	-10000	0	-10000	0	0
MAP3K14	0.001	0.13	-10000	0	-0.28	52	52
PDPK1	-0.025	0.2	-10000	0	-0.44	59	59
TCR/CD3/MHC I/CD8/Fyn	-0.12	0.39	-10000	0	-0.88	64	64

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.011	0.13	-9999	-0.39	26	26
NF kappa B1 p50/RelA/I kappa B alpha	0.013	0.11	-9999	-0.33	10	10
AP1	-0.15	0.21	-9999	-0.53	58	58
mol:PIP3	-0.06	0.13	-9999	-0.46	22	22
AKT1	0.032	0.097	-9999	-0.4	8	8
PTK2B	-0.004	0.099	-9999	-0.23	46	46
RHOA	0.018	0.05	-9999	-0.26	1	1
PIK3CB	0.015	0.001	-9999	-10000	0	0
mol:Ca2+	0.001	0.098	-9999	-0.26	32	32
MAGI3	0.015	0	-9999	-10000	0	0
RELA	0.016	0	-9999	-10000	0	0
apoptosis	-0.036	0.15	-9999	-0.32	67	67
HRAS/GDP	0.012	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	-0.012	0.12	-9999	-0.29	45	45
NF kappa B1 p50/RelA	-0.05	0.12	-9999	-0.44	17	17
endothelial cell migration	-0.05	0.22	-9999	-0.59	47	47
ADCY4	-0.1	0.22	-9999	-0.46	75	75
ADCY5	-0.23	0.3	-9999	-0.57	137	137
ADCY6	-0.1	0.22	-9999	-0.46	75	75
ADCY7	-0.1	0.22	-9999	-0.46	75	75
ADCY1	-0.11	0.22	-9999	-0.45	79	79
ADCY2	-0.2	0.28	-9999	-0.54	123	123
ADCY3	-0.1	0.22	-9999	-0.46	75	75
ADCY8	-0.11	0.22	-9999	-0.46	75	75
ADCY9	-0.11	0.22	-9999	-0.47	76	76
GSK3B	0.005	0.094	-9999	-0.3	17	17
arachidonic acid secretion	-0.11	0.22	-9999	-0.46	77	77
GNG2	0.005	0.076	-9999	-0.57	6	6
TRIP6	0.023	0.023	-9999	-10000	0	0
GNAO1	-0.13	0.23	-9999	-0.4	132	132
HRAS	0.016	0	-9999	-10000	0	0
NFKBIA	0.002	0.12	-9999	-0.31	31	31
GAB1	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.001	0.069	-9999	-0.92	2	2
JUN	-0.006	0.11	-9999	-0.58	13	13
LPA/LPA2/NHERF2	-0.009	0.036	-9999	-0.33	3	3
TIAM1	-0.003	0.082	-9999	-1.1	2	2
PIK3R1	0.015	0.001	-9999	-10000	0	0
mol:IP3	0.001	0.099	-9999	-0.26	32	32
PLCB3	0.023	0.038	-9999	-0.29	3	3
FOS	-0.17	0.27	-9999	-0.58	110	110
positive regulation of mitosis	-0.11	0.22	-9999	-0.46	77	77
LPA/LPA1-2-3	-0.041	0.16	-9999	-0.37	55	55
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.016	0	-9999	-10000	0	0
stress fiber formation	-0.005	0.12	-9999	-0.34	24	24
GNAZ	-0.093	0.2	-9999	-0.38	110	110
EGFR/PI3K-beta/Gab1	-0.062	0.13	-9999	-0.48	22	22
positive regulation of dendritic cell cytokine production	-0.069	0.15	-9999	-0.37	54	54
LPA/LPA2/MAGI-3	-0.007	0.037	-9999	-0.33	3	3
ARHGEF1	0.004	0.11	-9999	-0.35	21	21
GNAI2	-0.015	0.13	-9999	-0.33	47	47
GNAI3	-0.015	0.13	-9999	-0.33	47	47
GNAI1	-0.018	0.13	-9999	-0.33	50	50
LPA/LPA3	-0.048	0.12	-9999	-0.42	34	34
LPA/LPA2	-0.011	0.046	-9999	-0.4	3	3
LPA/LPA1	-0.052	0.14	-9999	-0.4	47	47
HB-EGF/EGFR	-0.085	0.18	-9999	-0.34	111	111
HBEGF	-0.093	0.19	-9999	-0.38	105	105
mol:DAG	0.001	0.099	-9999	-0.26	32	32
cAMP biosynthetic process	-0.15	0.26	-9999	-0.46	122	122
NFKB1	0.016	0	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
GNB1	0.015	0.001	-9999	-10000	0	0
LYN	0.002	0.12	-9999	-0.31	31	31
GNAQ	-0.01	0.096	-9999	-0.28	37	37
LPAR2	0.011	0.048	-9999	-0.51	3	3
LPAR3	-0.04	0.17	-9999	-0.57	34	34
LPAR1	-0.03	0.16	-9999	-0.62	21	21
IL8	-0.12	0.23	-9999	-0.48	80	80
PTK2	-0.027	0.15	-9999	-0.36	46	46
Rac1/GDP	0.012	0	-9999	-10000	0	0
CASP3	-0.036	0.15	-9999	-0.32	67	67
EGFR	-0.008	0.11	-9999	-0.54	15	15
PLCG1	-0.02	0.11	-9999	-0.29	43	43
PLD2	-0.027	0.15	-9999	-0.36	46	46
G12/G13	-0.005	0.12	-9999	-0.38	21	21
PI3K-beta	-0.031	0.088	-9999	-0.46	8	8
cell migration	-0.017	0.053	-9999	-0.21	9	9
SLC9A3R2	0.016	0	-9999	-10000	0	0
PXN	-0.005	0.12	-9999	-0.34	24	24
HRAS/GTP	-0.11	0.23	-9999	-0.48	77	77
RAC1	0.016	0	-9999	-10000	0	0
MMP9	-0.13	0.24	-9999	-0.51	97	97
PRKCE	0.016	0	-9999	-10000	0	0
PRKCD	0.009	0.095	-9999	-0.33	6	6
Gi(beta/gamma)	-0.1	0.22	-9999	-0.45	77	77
mol:LPA	-0.011	0.052	-9999	-0.19	26	26
TRIP6/p130 Cas/FAK1/Paxillin	-0.048	0.12	-9999	-0.49	15	15
MAPKKK cascade	-0.11	0.22	-9999	-0.46	77	77
contractile ring contraction involved in cytokinesis	0.018	0.049	-9999	-0.26	1	1
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.055	0.15	-9999	-0.32	82	82
GNA15	-0.012	0.099	-9999	-0.28	39	39
GNA12	0.015	0	-9999	-10000	0	0
GNA13	0.015	0	-9999	-10000	0	0
MAPT	-0.013	0.12	-9999	-0.29	45	45
GNA11	-0.011	0.1	-9999	-0.29	37	37
Rac1/GTP	0.025	0.075	-9999	-0.98	2	2
MMP2	-0.05	0.22	-9999	-0.6	47	47

×

Glucocorticoid receptor regulatory network

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
PCK2	0.015	0.062	0.28	4	-0.35	1	5
SMARCC2	0.015	0.015	-10000	0	-10000	0	0
SMARCC1	0.015	0.016	-10000	0	-10000	0	0
TBX21	-0.086	0.22	-10000	0	-0.74	29	29
SUMO2	0.011	0.008	-10000	0	-10000	0	0
STAT1 (dimer)	0.02	0.055	-10000	0	-0.49	4	4
FKBP4	0.016	0	-10000	0	-10000	0	0
FKBP5	-0.013	0.13	-10000	0	-0.58	17	17
GR alpha/HSP90/FKBP51/HSP90	0.084	0.12	0.28	17	-0.38	3	20
PRL	-0.059	0.12	-10000	0	-0.46	10	10
cortisol/GR alpha (dimer)/TIF2	0.22	0.22	0.48	94	-0.42	2	96
RELA	-0.098	0.12	-10000	0	-0.29	19	19
FGG	0.16	0.22	0.44	54	-0.48	9	63
GR beta/TIF2	0.079	0.15	0.29	26	-0.36	20	46
IFNG	-0.32	0.25	-10000	0	-0.66	87	87
apoptosis	-0.07	0.18	0.44	3	-0.53	14	17
CREB1	0.014	0.031	-10000	0	-10000	0	0
histone acetylation	-0.011	0.14	0.5	1	-0.44	14	15
BGLAP	-0.041	0.11	-10000	0	-0.51	1	1
GR/PKAc	0.1	0.089	0.27	17	-10000	0	17
NF kappa B1 p50/RelA	-0.18	0.23	-10000	0	-0.45	120	120
SMARCD1	0.015	0.016	-10000	0	-10000	0	0
MDM2	0.089	0.088	0.24	27	-0.24	3	30
GATA3	-0.02	0.15	-10000	0	-0.57	25	25
AKT1	0.002	0.006	-10000	0	-10000	0	0
CSF2	-0.078	0.13	-10000	0	-0.45	5	5
GSK3B	0.011	0.008	-10000	0	-10000	0	0
NR1I3	-0.026	0.18	0.46	1	-0.49	9	10
CSN2	0.16	0.14	0.36	49	-10000	0	49
BRG1/BAF155/BAF170/BAF60A	0.039	0.053	-10000	0	-0.32	2	2
NFATC1	-0.011	0.13	-10000	0	-0.57	17	17
POU2F1	0.017	0.011	-10000	0	-10000	0	0
CDKN1A	0.037	0.082	-10000	0	-1.4	1	1
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.003	0.006	-10000	0	-10000	0	0
SFN	-0.034	0.15	-10000	0	-0.52	33	33
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.073	0.13	0.27	16	-0.49	1	17
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.16	0.39	0.44	1	-0.84	87	88
JUN	-0.17	0.17	-10000	0	-0.48	53	53
IL4	-0.085	0.15	-10000	0	-0.57	14	14
CDK5R1	-0.016	0.12	-10000	0	-0.51	20	20
PRKACA	0.016	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.24	0.29	0.21	1	-0.57	121	122
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.094	0.11	0.29	13	-0.49	1	14
cortisol/GR alpha (monomer)	0.27	0.24	0.55	106	-10000	0	106
NCOA2	-0.023	0.14	-10000	0	-0.58	23	23
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.23	0.28	-10000	0	-0.63	110	110
AP-1/NFAT1-c-4	-0.4	0.32	-10000	0	-0.72	146	146
AFP	-0.14	0.15	-10000	0	-0.57	13	13
SUV420H1	0.016	0	-10000	0	-10000	0	0
IRF1	0.16	0.12	0.44	11	-10000	0	11
TP53	0.04	0.028	-10000	0	-0.49	1	1
PPP5C	0.016	0	-10000	0	-10000	0	0
KRT17	-0.36	0.38	-10000	0	-0.94	73	73
KRT14	-0.24	0.24	-10000	0	-0.57	67	67
TBP	0.026	0.012	-10000	0	-10000	0	0
CREBBP	0.071	0.087	0.32	2	-10000	0	2
HDAC1	0.014	0.008	-10000	0	-10000	0	0
HDAC2	0.019	0.013	-10000	0	-10000	0	0
AP-1	-0.41	0.33	-10000	0	-0.72	147	147
MAPK14	0.012	0.007	-10000	0	-10000	0	0
MAPK10	-0.04	0.17	-10000	0	-0.58	31	31
MAPK11	0.011	0.008	-10000	0	-10000	0	0
KRT5	-0.57	0.55	-10000	0	-1.1	153	153
interleukin-1 receptor activity	0.004	0.013	-10000	0	-10000	0	0
NCOA1	0.019	0.003	-10000	0	-10000	0	0
STAT1	0.02	0.055	-10000	0	-0.49	4	4
CGA	-0.071	0.13	-10000	0	-0.58	3	3
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.12	0.15	0.34	67	-0.47	2	69
MAPK3	0.011	0.007	-10000	0	-10000	0	0
MAPK1	0.012	0.007	-10000	0	-10000	0	0
ICAM1	-0.24	0.25	-10000	0	-0.55	99	99
NFKB1	-0.098	0.12	-10000	0	-0.29	20	20
MAPK8	-0.13	0.14	-10000	0	-0.39	44	44
MAPK9	0.012	0.007	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.081	0.18	0.44	3	-0.56	14	17
BAX	0.041	0.031	-10000	0	-10000	0	0
POMC	-0.3	0.3	-10000	0	-0.82	39	39
EP300	0.071	0.087	0.29	4	-10000	0	4
cortisol/GR alpha (dimer)/p53	0.26	0.2	0.5	103	-10000	0	103
proteasomal ubiquitin-dependent protein catabolic process	0.061	0.07	0.22	5	-0.23	2	7
SGK1	0.088	0.29	-10000	0	-1.3	13	13
IL13	-0.24	0.22	-10000	0	-0.76	30	30
IL6	-0.6	0.6	-10000	0	-1.2	175	175
PRKACG	0.002	0.005	-10000	0	-10000	0	0
IL5	-0.21	0.19	-10000	0	-0.7	19	19
IL2	-0.28	0.22	-10000	0	-0.63	59	59
CDK5	0.014	0.003	-10000	0	-10000	0	0
PRKACB	0.012	0.044	-10000	0	-0.58	2	2
HSP90AA1	0.016	0	-10000	0	-10000	0	0
IL8	-0.35	0.45	-10000	0	-0.87	111	111
CDK5R1/CDK5	-0.005	0.087	-10000	0	-0.36	20	20
NF kappa B1 p50/RelA/PKAc	-0.11	0.18	-10000	0	-0.38	46	46
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.24	0.19	0.46	103	-10000	0	103
SMARCA4	0.015	0.015	-10000	0	-10000	0	0
chromatin remodeling	0.16	0.14	0.35	51	-0.42	4	55
NF kappa B1 p50/RelA/Cbp	-0.076	0.23	0.39	1	-0.5	27	28
JUN (dimer)	-0.17	0.17	-10000	0	-0.47	53	53
YWHAH	0.016	0	-10000	0	-10000	0	0
VIPR1	-0.076	0.2	-10000	0	-0.67	28	28
NR3C1	0.15	0.15	0.38	51	-0.43	3	54
NR4A1	-0.32	0.3	-10000	0	-0.58	201	201
TIF2/SUV420H1	-0.005	0.11	-10000	0	-0.41	23	23
MAPKKK cascade	-0.07	0.18	0.44	3	-0.53	14	17
cortisol/GR alpha (dimer)/Src-1	0.25	0.2	0.48	103	-10000	0	103
PBX1	-0.008	0.12	-10000	0	-0.57	15	15
POU1F1	0.003	0.04	-10000	0	-0.5	2	2
SELE	-0.56	0.59	-10000	0	-1.2	155	155
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.16	0.14	0.35	51	-0.43	4	55
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.24	0.19	0.46	103	-10000	0	103
mol:cortisol	0.14	0.14	0.3	110	-10000	0	110
MMP1	-0.26	0.18	-10000	0	-0.47	100	100

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.079	0.21	-9999	-0.59	51	51
PDGF/PDGFRA/CRKL	-0.046	0.16	-9999	-0.42	52	52
positive regulation of JUN kinase activity	-0.014	0.12	-9999	-0.32	22	22
CRKL	0.013	0.039	-9999	-0.51	2	2
PDGF/PDGFRA/Caveolin-3	-0.056	0.16	-9999	-0.43	53	53
AP1	-0.34	0.47	-9999	-1	110	110
mol:IP3	-0.053	0.16	-9999	-0.44	51	51
PLCG1	-0.053	0.16	-9999	-0.44	51	51
PDGF/PDGFRA/alphaV Integrin	-0.045	0.16	-9999	-0.42	51	51
RAPGEF1	0.016	0	-9999	-10000	0	0
CRK	0.016	0	-9999	-10000	0	0
mol:Ca2+	-0.052	0.16	-9999	-0.44	51	51
CAV3	0	0.047	-9999	-0.51	3	3
CAV1	-0.013	0.13	-9999	-0.58	17	17
SHC/Grb2/SOS1	-0.013	0.12	-9999	-0.32	22	22
PDGF/PDGFRA/Shf	-0.049	0.16	-9999	-0.44	53	53
FOS	-0.3	0.48	-9999	-1	110	110
JUN	-0.037	0.092	-9999	-0.49	13	13
oligodendrocyte development	-0.044	0.16	-9999	-0.42	51	51
GRB2	0.016	0	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
mol:DAG	-0.053	0.16	-9999	-0.44	51	51
PDGF/PDGFRA	-0.079	0.21	-9999	-0.59	51	51
actin cytoskeleton reorganization	-0.043	0.15	-9999	-0.42	51	51
SRF	0.033	0.012	-9999	-10000	0	0
SHC1	0.014	0.028	-9999	-0.51	1	1
PI3K	-0.025	0.13	-9999	-0.34	51	51
PDGF/PDGFRA/Crk/C3G	-0.025	0.13	-9999	-0.34	51	51
JAK1	-0.041	0.15	-9999	-0.42	51	51
ELK1/SRF	-0.011	0.13	-9999	-0.32	51	51
SHB	0.016	0	-9999	-10000	0	0
SHF	0.007	0.07	-9999	-0.58	5	5
CSNK2A1	0.022	0.028	-9999	-10000	0	0
GO:0007205	-0.057	0.17	-9999	-0.46	51	51
SOS1	0.016	0	-9999	-10000	0	0
Ras protein signal transduction	-0.014	0.12	-9999	-0.32	22	22
PDGF/PDGFRA/SHB	-0.044	0.15	-9999	-0.42	51	51
PDGF/PDGFRA/Caveolin-1	-0.062	0.19	-9999	-0.47	59	59
ITGAV	0.014	0.031	-9999	-0.58	1	1
ELK1	-0.051	0.16	-9999	-0.41	51	51
PIK3CA	0.016	0	-9999	-10000	0	0
PDGF/PDGFRA/Crk	-0.044	0.15	-9999	-0.42	51	51
JAK-STAT cascade	-0.041	0.15	-9999	-0.41	51	51
cell proliferation	-0.049	0.16	-9999	-0.44	53	53

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.018	0.025	-9999	-0.41	1	1
PDGFRB	-0.003	0.094	-9999	-0.58	9	9
SPHK1	-0.035	0.064	-9999	-1.1	1	1
mol:S1P	-0.041	0.066	-9999	-0.67	2	2
S1P1/S1P/Gi	-0.19	0.27	-9999	-0.48	133	133
GNAO1	-0.17	0.28	-9999	-0.58	110	110
PDGFB-D/PDGFRB/PLCgamma1	-0.16	0.25	-9999	-0.5	89	89
PLCG1	-0.17	0.25	-9999	-0.45	133	133
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.003	0.093	-9999	-0.58	9	9
GNAI2	0.012	0.007	-9999	-10000	0	0
GNAI3	0.012	0.007	-9999	-10000	0	0
GNAI1	0.007	0.055	-9999	-0.58	3	3
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.015	0.023	-9999	-0.35	1	1
S1P1/S1P	-0.043	0.071	-9999	-0.47	3	3
negative regulation of cAMP metabolic process	-0.18	0.26	-9999	-0.47	133	133
MAPK3	-0.22	0.32	-9999	-0.59	131	131
calcium-dependent phospholipase C activity	-0.003	0.004	-9999	-10000	0	0
Rac1/GDP	0.012	0	-9999	-10000	0	0
RhoA/GDP	0.012	0	-9999	-10000	0	0
KDR	0.013	0.031	-9999	-0.58	1	1
PLCB2	-0.015	0.082	-9999	-0.36	5	5
RAC1	0.016	0	-9999	-10000	0	0
RhoA/GTP	-0.034	0.059	-9999	-0.39	3	3
receptor internalization	-0.041	0.067	-9999	-0.43	3	3
PTGS2	-0.32	0.48	-9999	-0.88	129	129
Rac1/GTP	-0.034	0.059	-9999	-0.39	3	3
RHOA	0.016	0	-9999	-10000	0	0
VEGFA	0.014	0.004	-9999	-10000	0	0
negative regulation of T cell proliferation	-0.18	0.26	-9999	-0.47	133	133
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.11	0.24	-9999	-0.58	76	76
MAPK1	-0.22	0.32	-9999	-0.59	131	131
S1P1/S1P/PDGFB-D/PDGFRB	-0.033	0.11	-9999	-0.45	9	9
ABCC1	0.01	0.039	-9999	-0.51	2	2

×

Neurotrophic factor-mediated Trk receptor signaling

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
CRKL	0.013	0.039	-10000	0	-0.51	2	2
RAS family/GTP/Tiam1	-0.085	0.12	-10000	0	-0.27	44	44
NT3 (dimer)/TRKC	-0.26	0.28	-10000	0	-0.49	198	198
NT3 (dimer)/TRKB	-0.26	0.3	-10000	0	-0.49	200	200
SHC/Grb2/SOS1/GAB1/PI3K	0.043	0.008	-10000	0	-10000	0	0
RAPGEF1	0.016	0	-10000	0	-10000	0	0
BDNF	-0.099	0.23	-10000	0	-0.58	69	69
PIK3CA	0.016	0	-10000	0	-10000	0	0
DYNLT1	0.016	0	-10000	0	-10000	0	0
NTRK1	0.006	0.061	-10000	0	-0.51	5	5
NTRK2	-0.22	0.29	-10000	0	-0.57	143	143
NTRK3	-0.28	0.29	-10000	0	-0.58	175	175
NT-4/5 (dimer)/TRKB	-0.22	0.27	-10000	0	-0.45	188	188
neuron apoptosis	0.18	0.25	0.52	103	-10000	0	103
SHC 2-3/Grb2	-0.2	0.28	-10000	0	-0.58	103	103
SHC1	0.014	0.028	-10000	0	-0.51	1	1
SHC2	-0.21	0.28	-10000	0	-0.63	86	86
SHC3	-0.21	0.26	-10000	0	-0.58	98	98
STAT3 (dimer)	0.011	0.063	-10000	0	-0.34	7	7
NT3 (dimer)/TRKA	-0.13	0.22	-10000	0	-0.4	131	131
RIN/GDP	-0.065	0.1	-10000	0	-0.25	27	27
GIPC1	0.016	0	-10000	0	-10000	0	0
KRAS	0.014	0.028	-10000	0	-0.51	1	1
DNAJA3	-0.1	0.16	-10000	0	-0.37	80	80
RIN/GTP	0	0.02	-10000	0	-0.37	1	1
CCND1	0.007	0.14	-10000	0	-0.55	18	18
MAGED1	0.016	0	-10000	0	-10000	0	0
PTPN11	0.016	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.026	0.15	-10000	0	-0.57	25	25
SHC/GRB2/SOS1	0.031	0.017	-10000	0	-0.29	1	1
GRB2	0.016	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.052	0.17	-10000	0	-0.38	72	72
TRKA/NEDD4-2	0.016	0.044	-10000	0	-0.36	5	5
ELMO1	0.012	0.044	-10000	0	-0.58	2	2
RhoG/GTP/ELMO1/DOCK1	0.018	0.042	-10000	0	-0.52	2	2
NGF	-0.063	0.2	-10000	0	-0.58	47	47
HRAS	0.016	0	-10000	0	-10000	0	0
DOCK1	0.014	0.031	-10000	0	-0.58	1	1
GAB2	0.016	0	-10000	0	-10000	0	0
RIT2	0	0.027	-10000	0	-0.51	1	1
RIT1	0.016	0	-10000	0	-10000	0	0
FRS2	0.005	0.072	-10000	0	-0.51	7	7
DNM1	0.001	0.093	-10000	0	-0.58	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.016	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.1	0.16	-10000	0	-0.36	84	84
mol:GDP	-0.095	0.15	-10000	0	-0.37	33	33
NGF (dimer)	-0.063	0.2	-10000	0	-0.57	47	47
RhoG/GDP	0.009	0.033	-10000	0	-0.42	2	2
RIT1/GDP	-0.058	0.1	-10000	0	-0.25	24	24
TIAM1	0.012	0.044	-10000	0	-0.58	2	2
PIK3R1	0.016	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.18	0.24	-10000	0	-0.41	174	174
KIDINS220/CRKL/C3G	0.021	0.028	-10000	0	-0.36	2	2
SHC/RasGAP	0.022	0.02	-10000	0	-0.36	1	1
FRS2 family/SHP2	0.025	0.045	-10000	0	-0.29	7	7
SHC/GRB2/SOS1/GAB1	0.039	0.016	-10000	0	-10000	0	0
RIT1/GTP	0.012	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.092	0.23	-10000	0	-0.57	65	65
RAP1/GDP	-0.067	0.068	-10000	0	-0.23	3	3
KIDINS220/CRKL	0.013	0.039	-10000	0	-0.51	2	2
BDNF (dimer)	-0.099	0.23	-10000	0	-0.57	69	69
ubiquitin-dependent protein catabolic process	-0.024	0.13	-10000	0	-0.34	52	52
Schwann cell development	-0.054	0.036	-10000	0	-10000	0	0
EHD4	0.016	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.034	0.041	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.044	0.02	-10000	0	-10000	0	0
RAP1B	0.016	0	-10000	0	-10000	0	0
RAP1A	0.016	0	-10000	0	-10000	0	0
CDC42/GTP	-0.33	0.28	-10000	0	-0.62	147	147
ABL1	0.016	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.023	0	-10000	0	-10000	0	0
Rap1/GTP	-0.064	0.074	-10000	0	-10000	0	0
STAT3	0.011	0.063	-10000	0	-0.34	7	7
axon guidance	-0.31	0.26	-10000	0	-0.59	147	147
MAPK3	-0.038	0.16	-10000	0	-0.35	62	62
MAPK1	-0.038	0.16	-10000	0	-0.35	62	62
CDC42/GDP	-0.058	0.1	-10000	0	-0.25	24	24
NTF3	-0.093	0.23	-10000	0	-0.57	65	65
NTF4	-0.026	0.15	-10000	0	-0.58	25	25
NGF (dimer)/TRKA/FAIM	-0.024	0.13	-10000	0	-0.34	52	52
PI3K	0.023	0	-10000	0	-10000	0	0
FRS3	0.016	0	-10000	0	-10000	0	0
FAIM	0.016	0	-10000	0	-10000	0	0
GAB1	0.016	0	-10000	0	-10000	0	0
RASGRF1	-0.14	0.17	-10000	0	-0.38	85	85
SOS1	0.016	0	-10000	0	-10000	0	0
MCF2L	-0.23	0.26	-10000	0	-0.43	200	200
RGS19	0.014	0.028	-10000	0	-0.51	1	1
CDC42	0.016	0	-10000	0	-10000	0	0
RAS family/GTP	0.01	0.073	-10000	0	-10000	0	0
Rac1/GDP	-0.058	0.1	-10000	0	-0.25	24	24
NGF (dimer)/TRKA/GRIT	-0.034	0.13	-10000	0	-0.35	52	52
neuron projection morphogenesis	-0.073	0.18	-10000	0	-0.53	21	21
NGF (dimer)/TRKA/NEDD4-2	-0.024	0.13	-10000	0	-0.34	52	52
MAP2K1	0.045	0.014	-10000	0	-10000	0	0
NGFR	-0.12	0.25	-10000	0	-0.57	84	84
NGF (dimer)/TRKA/GIPC/GAIP	-0.004	0.11	-10000	0	-0.32	18	18
RAS family/GTP/PI3K	0.036	0.008	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	0.041	0.038	-10000	0	-10000	0	0
NRAS	0.016	0	-10000	0	-10000	0	0
GRB2/SOS1	0.023	0	-10000	0	-10000	0	0
PRKCI	0.016	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
PRKCZ	0.012	0.044	-10000	0	-0.58	2	2
MAPKKK cascade	-0.12	0.24	-10000	0	-0.72	47	47
RASA1	0.016	0	-10000	0	-10000	0	0
TRKA/c-Abl	0.016	0.044	-10000	0	-0.36	5	5
SQSTM1	0.016	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.16	0.22	-10000	0	-0.38	167	167
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.003	0.12	-10000	0	-0.3	16	16
MATK	-0.031	0.16	-10000	0	-0.56	29	29
NEDD4L	0.016	0	-10000	0	-10000	0	0
RAS family/GDP	-0.063	0.064	-10000	0	-0.23	2	2
NGF (dimer)/TRKA	-0.11	0.18	-10000	0	-0.35	111	111
Rac1/GTP	-0.11	0.11	-10000	0	-0.29	71	71
FRS2 family/SHP2/CRK family	0.039	0.043	-10000	0	-10000	0	0

×

S1P5 pathway

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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.11	0.16	0.43	50	-10000	0	50
GNAI2	0.016	0	-10000	0	-10000	0	0
S1P/S1P5/G12	0.008	0.064	-10000	0	-0.31	14	14
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.17	0.27	-10000	0	-0.58	110	110
RhoA/GTP	-0.089	0.18	-10000	0	-0.44	50	50
negative regulation of cAMP metabolic process	-0.1	0.19	-10000	0	-0.35	112	112
GNAZ	-0.11	0.24	-10000	0	-0.58	76	76
GNAI3	0.016	0	-10000	0	-10000	0	0
GNA12	0.016	0	-10000	0	-10000	0	0
S1PR5	-0.005	0.1	-10000	0	-0.52	14	14
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.11	0.2	-10000	0	-0.35	112	112
RhoA/GDP	0.012	0	-10000	0	-10000	0	0
RHOA	0.016	0	-10000	0	-10000	0	0
GNAI1	0.011	0.054	-10000	0	-0.58	3	3

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.019	0.029	-9999	-10000	0	0
VDR	0.012	0.042	-9999	-0.54	2	2
FAM120B	0.016	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.013	0.13	-9999	-0.39	7	7
RXRs/LXRs/DNA/Oxysterols	0.006	0.12	-9999	-0.39	7	7
MED1	0.016	0	-9999	-10000	0	0
mol:9cRA	0.006	0.007	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	0.008	0.11	-9999	-0.28	40	40
RXRs/NUR77	-0.23	0.22	-9999	-0.37	241	241
RXRs/PPAR	-0.047	0.14	-9999	-0.38	15	15
NCOR2	0.016	0	-9999	-10000	0	0
VDR/VDR/Vit D3	0.009	0.03	-9999	-0.4	2	2
RARs/VDR/DNA/Vit D3	0.011	0.088	-9999	-0.29	28	28
RARA	0.016	0	-9999	-10000	0	0
NCOA1	0.016	0	-9999	-10000	0	0
VDR/VDR/DNA	0.012	0.042	-9999	-0.54	2	2
RARs/RARs/DNA/9cRA	0.006	0.086	-9999	-0.29	27	27
RARG	0.016	0	-9999	-10000	0	0
RPS6KB1	0.028	0.044	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	0.008	0.11	-9999	-0.28	40	40
THRA	0.016	0	-9999	-10000	0	0
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	0.009	0.03	-9999	-0.4	2	2
RXRs/PPAR/9cRA/PGJ2/DNA	-0.047	0.16	-9999	-0.3	95	95
NR1H4	-0.12	0.24	-9999	-0.56	83	83
RXRs/LXRs/DNA	-0.017	0.15	-9999	-0.38	7	7
NR1H2	0.022	0.005	-9999	-10000	0	0
NR1H3	0.022	0.005	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.042	0.15	-9999	-0.28	96	96
NR4A1	-0.32	0.29	-9999	-0.58	200	200
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.084	0.16	-9999	-0.32	77	77
RXRG	-0.14	0.26	-9999	-0.57	95	95
RXR alpha/CCPG	0.026	0.024	-9999	-0.41	1	1
RXRA	0.02	0.032	-9999	-0.57	1	1
RXRB	0.022	0.005	-9999	-10000	0	0
THRB	-0.016	0.13	-9999	-0.58	19	19
PPARG	-0.024	0.15	-9999	-0.57	24	24
PPARD	0.016	0	-9999	-10000	0	0
TNF	0.008	0.13	-9999	-0.48	6	6
mol:Oxysterols	0.007	0.006	-9999	-10000	0	0
cholesterol transport	0.006	0.12	-9999	-0.38	7	7
PPARA	0.012	0.044	-9999	-0.58	2	2
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	-0.029	0.16	-9999	-0.58	27	27
RXRs/NUR77/BCL2	-0.21	0.2	-9999	-0.32	243	243
SREBF1	0.015	0.11	-9999	-0.47	2	2
RXRs/RXRs/DNA/9cRA	-0.046	0.16	-9999	-0.3	95	95
ABCA1	0.016	0.11	-9999	-0.46	1	1
RARs/THRs	0.005	0.12	-9999	-0.58	6	6
RXRs/FXR	-0.12	0.21	-9999	-0.36	141	141
BCL2	-0.008	0.12	-9999	-0.58	14	14

×

IL12-mediated signaling events

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
IL12/IL12R/TYK2/JAK2/SOCS1	-0.011	0.12	-10000	0	-0.35	19	19
TBX21	-0.15	0.5	-10000	0	-1.2	56	56
B2M	0.016	0.008	-10000	0	-10000	0	0
TYK2	0.017	0.023	-10000	0	-10000	0	0
IL12RB1	-0.02	0.15	-10000	0	-0.56	24	24
GADD45B	-0.081	0.39	-10000	0	-0.96	42	42
IL12RB2	-0.071	0.2	-10000	0	-0.52	59	59
GADD45G	-0.077	0.37	-10000	0	-0.9	43	43
natural killer cell activation	0.001	0.026	-10000	0	-10000	0	0
RELB	0.016	0	-10000	0	-10000	0	0
RELA	0.016	0	-10000	0	-10000	0	0
IL18	0.011	0.072	-10000	0	-0.59	5	5
IL2RA	-0.036	0.16	-10000	0	-0.55	33	33
IFNG	-0.087	0.2	-10000	0	-0.51	68	68
STAT3 (dimer)	-0.078	0.36	-10000	0	-0.76	60	60
HLA-DRB5	-0.028	0.14	-10000	0	-0.55	25	25
FASLG	-0.16	0.51	-10000	0	-1.2	63	63
NF kappa B2 p52/RelB	-0.2	0.39	-10000	0	-0.98	61	61
CD4	0.009	0.045	-10000	0	-0.58	2	2
SOCS1	0.014	0.028	-10000	0	-0.51	1	1
EntrezGene:6955	-0.007	0.016	-10000	0	-10000	0	0
CD3D	-0.051	0.18	-10000	0	-0.57	38	38
CD3E	-0.055	0.19	-10000	0	-0.58	40	40
CD3G	-0.059	0.19	-10000	0	-0.58	42	42
IL12Rbeta2/JAK2	-0.04	0.15	-10000	0	-0.37	60	60
CCL3	-0.15	0.5	-10000	0	-1.1	59	59
CCL4	-0.18	0.55	-10000	0	-1.3	62	62
HLA-A	0.014	0.032	-10000	0	-0.58	1	1
IL18/IL18R	0.035	0.13	-10000	0	-0.4	24	24
NOS2	-0.12	0.42	-10000	0	-1	48	48
IL12/IL12R/TYK2/JAK2/SPHK2	-0.011	0.12	-10000	0	-0.35	19	19
IL1R1	-0.12	0.44	-10000	0	-1	54	54
IL4	0.002	0.026	-10000	0	-10000	0	0
JAK2	0.015	0.039	-10000	0	-0.58	1	1
EntrezGene:6957	-0.006	0.015	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.14	0.4	-10000	0	-0.84	67	67
RAB7A	-0.031	0.31	-10000	0	-0.71	42	42
lysosomal transport	-0.026	0.3	-10000	0	-0.67	42	42
FOS	-0.42	0.66	-10000	0	-1.2	133	133
STAT4 (dimer)	-0.076	0.4	-10000	0	-0.82	63	63
STAT5A (dimer)	-0.24	0.4	-10000	0	-0.91	75	75
GZMA	-0.18	0.55	-10000	0	-1.3	58	58
GZMB	-0.16	0.5	-10000	0	-1.2	57	57
HLX	0.016	0	-10000	0	-10000	0	0
LCK	-0.15	0.5	-10000	0	-1.1	61	61
TCR/CD3/MHC II/CD4	-0.13	0.3	-10000	0	-0.63	65	65
IL2/IL2R	-0.017	0.14	-10000	0	-0.42	29	29
MAPK14	-0.062	0.38	-10000	0	-0.85	50	50
CCR5	-0.1	0.42	-10000	0	-1	46	46
IL1B	-0.03	0.16	-10000	0	-0.55	30	30
STAT6	-0.011	0.14	0.25	1	-0.28	39	40
STAT4	-0.016	0.13	-10000	0	-0.58	19	19
STAT3	0.016	0	-10000	0	-10000	0	0
STAT1	0.01	0.055	-10000	0	-0.51	4	4
NFKB1	0.016	0	-10000	0	-10000	0	0
NFKB2	0.016	0	-10000	0	-10000	0	0
IL12B	-0.004	0.091	-10000	0	-0.49	11	11
CD8A	-0.047	0.18	-10000	0	-0.58	38	38
CD8B	-0.042	0.18	-10000	0	-0.57	35	35
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.011	0.12	0.35	19	-10000	0	19
IL2RB	0.006	0.075	-10000	0	-0.56	6	6
proteasomal ubiquitin-dependent protein catabolic process	-0.061	0.36	-10000	0	-0.74	63	63
IL2RG	-0.011	0.12	-10000	0	-0.54	17	17
IL12	0.004	0.088	-10000	0	-0.35	17	17
STAT5A	0.014	0.031	-10000	0	-0.58	1	1
CD247	0	0.081	-10000	0	-0.57	7	7
IL2	0.004	0.007	-10000	0	-10000	0	0
SPHK2	0.014	0.028	-10000	0	-0.51	1	1
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.007	0.071	-10000	0	-0.5	6	6
IL12/IL12R/TYK2/JAK2	-0.17	0.57	-10000	0	-1.2	64	64
MAP2K3	-0.067	0.38	-10000	0	-0.84	51	51
RIPK2	0.016	0	-10000	0	-10000	0	0
MAP2K6	-0.071	0.38	-10000	0	-0.85	51	51
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.008	0.11	-10000	0	-0.58	12	12
IL18RAP	-0.013	0.14	-10000	0	-0.58	19	19
IL12Rbeta1/TYK2	-0.006	0.11	-10000	0	-0.41	24	24
EOMES	-0.073	0.32	-10000	0	-1.4	19	19
STAT1 (dimer)	-0.087	0.35	-10000	0	-0.74	62	62
T cell proliferation	-0.04	0.3	-10000	0	-0.62	54	54
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.014	0.056	-10000	0	-0.59	3	3
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.14	0.25	-10000	0	-0.65	57	57
ATF2	-0.046	0.35	-10000	0	-0.78	47	47

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.016	0.055	-9999	-0.28	12	12
RGS9BP	-0.011	0.12	-9999	-0.56	16	16
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0.001	0.004	-9999	-10000	0	0
mol:Na +	-0.11	0.18	-9999	-0.34	124	124
mol:ADP	0.011	0.021	-9999	-0.37	1	1
GNAT2	0.007	0.055	-9999	-0.51	4	4
RGS9-1/Gbeta5/R9AP	-0.065	0.17	-9999	-0.35	89	89
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0.006	0.038	-9999	-0.31	5	5
GRK7	0.011	0.028	-9999	-0.51	1	1
CNGB3	-0.13	0.23	-9999	-0.51	99	99
Cone Metarhodopsin II/X-Arrestin	0.002	0.005	-9999	-10000	0	0
mol:Ca2+	-0.11	0.18	-9999	-0.32	133	133
Cone PDE6	-0.053	0.14	-9999	-0.4	9	9
Cone Metarhodopsin II	0.008	0.016	-9999	-0.28	1	1
Na + (4 Units)	-0.11	0.18	-9999	-0.32	133	133
GNAT2/GDP	-0.051	0.15	-9999	-0.3	86	86
GNB5	0.016	0	-9999	-10000	0	0
mol:GMP (4 units)	0.007	0.034	-9999	-0.28	5	5
Cone Transducin	0.017	0.058	-9999	-0.29	12	12
SLC24A2	-0.017	0.12	-9999	-0.51	19	19
GNB3/GNGT2	0.013	0.064	-9999	-0.41	8	8
GNB3	0.009	0.061	-9999	-0.56	4	4
GNAT2/GTP	0.005	0.04	-9999	-0.37	4	4
CNGA3	-0.049	0.18	-9999	-0.58	36	36
ARR3	0.003	0.006	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.11	0.18	-9999	-0.34	124	124
mol:Pi	-0.065	0.17	-9999	-0.35	89	89
Cone CNG Channel	-0.098	0.14	-9999	-0.45	16	16
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.017	0.12	-9999	-0.51	19	19
RGS9	-0.11	0.24	-9999	-0.58	76	76
PDE6C	0.003	0.006	-9999	-10000	0	0
GNGT2	0.009	0.062	-9999	-0.58	4	4
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.001	0.028	-9999	-0.51	1	1

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.021	0.02	-9999	-0.35	1	1
ADCY5	-0.17	0.19	-9999	-0.35	183	183
ADCY6	0.023	0	-9999	-10000	0	0
ADCY7	0.023	0	-9999	-10000	0	0
ADCY1	0.013	0.054	-9999	-0.31	10	10
ADCY2	-0.12	0.18	-9999	-0.35	135	135
ADCY3	0.023	0	-9999	-10000	0	0
ADCY8	0.011	0.034	-9999	-0.3	4	4
PRKCE	0.013	0	-9999	-10000	0	0
ADCY9	0.017	0.044	-9999	-0.35	5	5
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.063	0.094	-9999	-0.28	7	7

×

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.089	0.16	-9999	-0.54	5	5
NF kappa B1 p50/RelA/I kappa B alpha	-0.053	0.14	-9999	-0.47	5	5
alphaV/beta3 Integrin/Osteopontin/Src	-0.14	0.17	-9999	-0.35	142	142
AP1	-0.17	0.25	-9999	-0.53	86	86
ILK	-0.1	0.16	-9999	-0.47	9	9
bone resorption	-0.073	0.15	-9999	-0.47	15	15
PTK2B	0.014	0.031	-9999	-0.58	1	1
PYK2/p130Cas	-0.1	0.13	-9999	-0.52	5	5
ITGAV	0.017	0.032	-9999	-0.58	1	1
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0	0.097	-9999	-0.41	19	19
alphaV/beta3 Integrin/Osteopontin	-0.15	0.16	-9999	-0.34	78	78
MAP3K1	-0.1	0.16	-9999	-0.3	75	75
JUN	-0.006	0.11	-9999	-0.58	13	13
MAPK3	-0.09	0.16	-9999	-0.36	24	24
MAPK1	-0.09	0.16	-9999	-0.34	37	37
Rac1/GDP	0.012	0	-9999	-10000	0	0
NFKB1	0.016	0	-9999	-10000	0	0
MAPK8	-0.092	0.16	-9999	-0.43	12	12
ITGB3	-0.051	0.19	-9999	-0.57	42	42
NFKBIA	-0.073	0.16	-9999	-0.53	5	5
FOS	-0.17	0.27	-9999	-0.58	110	110
CD44	-0.004	0.11	-9999	-0.57	12	12
CHUK	0.016	0	-9999	-10000	0	0
PLAU	-0.089	0.18	-9999	-0.81	1	1
NF kappa B1 p50/RelA	-0.096	0.1	-9999	-0.46	5	5
BCAR1	0.016	0	-9999	-10000	0	0
RELA	0.016	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.038	0.14	-9999	-0.41	42	42
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.11	0.16	-9999	-0.3	76	76
VAV3	-0.096	0.16	-9999	-0.48	11	11
MAP3K14	-0.1	0.17	-9999	-0.34	44	44
ROCK2	0.004	0.082	-9999	-0.58	7	7
SPP1	-0.19	0.26	-9999	-0.5	141	141
RAC1	0.016	0	-9999	-10000	0	0
Rac1/GTP	-0.081	0.15	-9999	-0.48	9	9
MMP2	-0.15	0.24	-9999	-0.56	63	63

×

BCR signaling 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
JUN	-0.054	0.17	-10000	0	-0.42	45	45
IKBKB	-0.006	0.076	-10000	0	-0.26	6	6
AKT1	-0.048	0.12	-10000	0	-0.24	72	72
IKBKG	-0.004	0.079	-10000	0	-0.28	6	6
CALM1	-0.044	0.14	-10000	0	-0.41	29	29
PIK3CA	0.016	0	-10000	0	-10000	0	0
MAP3K1	-0.089	0.24	-10000	0	-0.54	61	61
MAP3K7	0.016	0	-10000	0	-10000	0	0
mol:Ca2+	-0.056	0.14	-10000	0	-0.44	29	29
DOK1	0.014	0.028	-10000	0	-0.51	1	1
AP-1	-0.052	0.11	-10000	0	-0.25	49	49
LYN	0.016	0	-10000	0	-10000	0	0
BLNK	-0.001	0.098	-10000	0	-0.58	10	10
SHC1	0.014	0.028	-10000	0	-0.51	1	1
BCR complex	-0.096	0.22	-10000	0	-0.47	86	86
CD22	-0.19	0.32	-10000	0	-0.72	77	77
CAMK2G	-0.033	0.13	-10000	0	-0.4	23	23
CSNK2A1	0.016	0	-10000	0	-10000	0	0
INPP5D	0.004	0.082	-10000	0	-0.58	7	7
SHC/GRB2/SOS1	-0.074	0.14	-10000	0	-0.49	21	21
GO:0007205	-0.057	0.15	-10000	0	-0.45	29	29
SYK	0.012	0.044	-10000	0	-0.58	2	2
ELK1	-0.045	0.14	-10000	0	-0.42	29	29
NFATC1	-0.1	0.24	-10000	0	-0.52	67	67
B-cell antigen/BCR complex	-0.096	0.22	-10000	0	-0.47	86	86
PAG1/CSK	0.023	0	-10000	0	-10000	0	0
NFKBIB	0.01	0.029	-10000	0	-10000	0	0
HRAS	-0.039	0.14	-10000	0	-0.39	29	29
NFKBIA	0.01	0.029	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.016	0.024	-10000	0	-10000	0	0
RasGAP/Csk	-0.068	0.21	-10000	0	-0.59	35	35
mol:GDP	-0.054	0.14	-10000	0	-0.42	29	29
PTEN	0.016	0	-10000	0	-10000	0	0
CD79B	-0.02	0.14	-10000	0	-0.56	22	22
NF-kappa-B/RelA/I kappa B alpha	0.016	0.024	-10000	0	-10000	0	0
GRB2	0.016	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.12	0.24	-10000	0	-0.52	78	78
PIK3R1	0.016	0	-10000	0	-10000	0	0
mol:IP3	-0.057	0.15	-10000	0	-0.45	29	29
CSK	0.016	0	-10000	0	-10000	0	0
FOS	-0.12	0.19	-10000	0	-0.46	50	50
CHUK	-0.004	0.079	-10000	0	-0.28	6	6
IBTK	0.016	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.054	0.11	-10000	0	-0.47	15	15
PTPN6	-0.15	0.31	-10000	0	-0.68	74	74
RELA	0.016	0	-10000	0	-10000	0	0
BCL2A1	0.012	0.034	-10000	0	-0.1	21	21
VAV2	-0.18	0.28	-10000	0	-0.66	70	70
ubiquitin-dependent protein catabolic process	0.015	0.028	-10000	0	-10000	0	0
BTK	-0.064	0.27	0.36	5	-1.2	20	25
CD19	-0.19	0.3	-10000	0	-0.68	73	73
MAP4K1	-0.002	0.099	-10000	0	-0.56	11	11
CD72	-0.002	0.095	-10000	0	-0.51	12	12
PAG1	0.016	0	-10000	0	-10000	0	0
MAPK14	-0.065	0.2	-10000	0	-0.45	60	60
SH3BP5	0.014	0.031	-10000	0	-0.58	1	1
PIK3AP1	-0.054	0.18	-10000	0	-0.5	34	34
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.07	0.21	-10000	0	-0.43	78	78
RAF1	-0.03	0.13	-10000	0	-0.44	16	16
RasGAP/p62DOK/SHIP	-0.1	0.2	-10000	0	-0.6	36	36
CD79A	-0.12	0.24	-10000	0	-0.57	81	81
re-entry into mitotic cell cycle	-0.051	0.11	-10000	0	-0.24	50	50
RASA1	0.016	0	-10000	0	-10000	0	0
MAPK3	-0.009	0.11	-10000	0	-0.42	11	11
MAPK1	-0.009	0.11	-10000	0	-0.42	11	11
CD72/SHP1	-0.14	0.29	-10000	0	-0.65	72	72
NFKB1	0.016	0	-10000	0	-10000	0	0
MAPK8	-0.067	0.2	-10000	0	-0.46	57	57
actin cytoskeleton organization	-0.12	0.25	-10000	0	-0.57	62	62
NF-kappa-B/RelA	0.037	0.046	-10000	0	-10000	0	0
Calcineurin	-0.047	0.1	-10000	0	-0.47	11	11
PI3K	-0.16	0.21	-10000	0	-0.5	87	87
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.056	0.16	-10000	0	-0.45	33	33
SOS1	0.016	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.11	0.28	-10000	0	-0.77	46	46
DAPP1	-0.15	0.3	-10000	0	-0.89	43	43
cytokine secretion	-0.092	0.22	-10000	0	-0.48	67	67
mol:DAG	-0.057	0.15	-10000	0	-0.45	29	29
PLCG2	0.009	0.057	-10000	0	-0.52	4	4
MAP2K1	-0.019	0.12	-10000	0	-0.47	11	11
B-cell antigen/BCR complex/FcgammaRIIB	-0.099	0.24	-10000	0	-0.47	93	93
mol:PI-3-4-5-P3	-0.11	0.15	-10000	0	-0.34	87	87
ETS1	-0.022	0.12	-10000	0	-0.47	11	11
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.055	0.18	-10000	0	-0.57	21	21
B-cell antigen/BCR complex/LYN	-0.14	0.28	-10000	0	-0.54	85	85
MALT1	0.016	0	-10000	0	-10000	0	0
TRAF6	0.016	0	-10000	0	-10000	0	0
RAC1	-0.12	0.27	-10000	0	-0.63	61	61
B-cell antigen/BCR complex/LYN/SYK	-0.17	0.28	-10000	0	-0.65	75	75
CARD11	-0.053	0.15	-10000	0	-0.43	33	33
FCGR2B	-0.032	0.16	-10000	0	-0.57	29	29
PPP3CA	0.016	0	-10000	0	-10000	0	0
BCL10	0.016	0	-10000	0	-10000	0	0
IKK complex	0.006	0.039	-10000	0	-10000	0	0
PTPRC	-0.059	0.2	-10000	0	-0.57	45	45
PDPK1	-0.049	0.12	-10000	0	-0.26	49	49
PPP3CB	0.016	0	-10000	0	-10000	0	0
PPP3CC	0.016	0	-10000	0	-10000	0	0
POU2F2	0.016	0.026	-10000	0	-0.1	10	10

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.17	0.27	-9999	-0.58	110	110
CDC42/GTP	-0.087	0.18	-9999	-0.44	49	49
PLCG1	-0.089	0.19	-9999	-0.46	49	49
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.016	0	-9999	-10000	0	0
GNAI3	0.016	0	-9999	-10000	0	0
G12/G13	0.023	0	-9999	-10000	0	0
cell migration	-0.11	0.16	-9999	-0.44	49	49
S1PR5	-0.005	0.1	-9999	-0.52	14	14
S1PR4	0.005	0.078	-9999	-0.55	7	7
MAPK3	-0.089	0.19	-9999	-0.46	49	49
MAPK1	-0.089	0.19	-9999	-0.46	49	49
S1P/S1P5/Gi	-0.11	0.2	-9999	-0.35	112	112
GNAI1	0.011	0.054	-9999	-0.58	3	3
CDC42/GDP	0.012	0	-9999	-10000	0	0
S1P/S1P5/G12	0.008	0.064	-9999	-0.31	14	14
RHOA	0.031	0.042	-9999	-0.28	4	4
S1P/S1P4/Gi	-0.1	0.2	-9999	-0.35	111	111
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.11	0.24	-9999	-0.58	76	76
S1P/S1P4/G12/G13	0.024	0.045	-9999	-0.29	7	7
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.014	0.14	-9999	-0.35	47	47
MAP4K1	-0.002	0.099	-9999	-0.56	11	11
MAP3K8	0.011	0.054	-9999	-0.58	3	3
PRKCB	-0.16	0.27	-9999	-0.58	103	103
DBNL	0.016	0	-9999	-10000	0	0
CRKL	0.013	0.039	-9999	-0.51	2	2
MAP3K1	0.011	0.11	-9999	-0.59	5	5
JUN	-0.15	0.29	-9999	-0.56	114	114
MAP3K7	0.011	0.11	-9999	-0.59	5	5
GRAP2	-0.057	0.19	-9999	-0.58	44	44
CRK	0.016	0	-9999	-10000	0	0
MAP2K4	0.019	0.12	-9999	-0.54	6	6
LAT	0.014	0.028	-9999	-0.51	1	1
LCP2	0.012	0.044	-9999	-0.58	2	2
MAPK8	-0.16	0.3	-9999	-0.6	106	106
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.003	0.12	-9999	-0.63	5	5
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.005	0.14	-9999	-0.7	5	5

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.012	0.014	-9999	-10000	0	0
SVIL	0.008	0.056	-9999	-0.58	3	3
ZNF318	0.024	0.035	-9999	-10000	0	0
JMJD2C	-0.002	0.026	-9999	-0.079	28	28
T-DHT/AR/Ubc9	-0.12	0.19	-9999	-0.38	128	128
CARM1	0.015	0.002	-9999	-10000	0	0
PRDX1	0.016	0.002	-9999	-10000	0	0
PELP1	0.017	0.006	-9999	-10000	0	0
CTNNB1	0.013	0.011	-9999	-10000	0	0
AKT1	0.018	0.009	-9999	-10000	0	0
PTK2B	0.012	0.032	-9999	-0.58	1	1
MED1	0.018	0.011	-9999	-10000	0	0
MAK	0.012	0.084	-9999	-0.49	8	8
response to oxidative stress	0	0.002	-9999	-10000	0	0
HIP1	0.011	0.034	-9999	-0.57	1	1
GSN	0.002	0.077	-9999	-0.58	6	6
NCOA2	-0.023	0.14	-9999	-0.58	23	23
NCOA6	0.011	0.03	-9999	-0.51	1	1
DNA-PK	0.033	0.037	-9999	-10000	0	0
NCOA4	0.015	0.001	-9999	-10000	0	0
PIAS3	0.013	0.011	-9999	-10000	0	0
cell proliferation	-0.02	0.052	-9999	-0.21	3	3
XRCC5	0.017	0.008	-9999	-10000	0	0
UBE3A	0.011	0.021	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.15	0.23	-9999	-0.42	138	138
FHL2	-0.019	0.11	-9999	-1.2	1	1
RANBP9	0.013	0.013	-9999	-10000	0	0
JMJD1A	-0.012	0.058	-9999	-0.12	77	77
CDK6	-0.002	0.1	-9999	-0.58	11	11
TGFB1I1	-0.004	0.099	-9999	-0.58	10	10
T-DHT/AR/CyclinD1	-0.14	0.2	-9999	-0.39	140	140
XRCC6	0.017	0.008	-9999	-10000	0	0
T-DHT/AR	-0.13	0.22	-9999	-0.39	130	130
CTDSP1	0.015	0.003	-9999	-10000	0	0
CTDSP2	0.021	0.023	-9999	-10000	0	0
BRCA1	0.011	0.032	-9999	-0.53	1	1
TCF4	0.015	0.057	-9999	-0.58	3	3
CDKN2A	-0.24	0.26	-9999	-0.5	174	174
SRF	0.027	0.012	-9999	-10000	0	0
NKX3-1	-0.077	0.18	-9999	-1	7	7
KLK3	-0.059	0.31	-9999	-1.5	15	15
TMF1	0.015	0.003	-9999	-10000	0	0
HNRNPA1	0.019	0.013	-9999	-10000	0	0
AOF2	-0.004	0.015	-9999	-0.071	15	15
APPL1	0.031	0.02	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.12	0.2	-9999	-0.37	128	128
AR	-0.21	0.29	-9999	-0.59	128	128
UBA3	0.015	0.003	-9999	-10000	0	0
PATZ1	0.019	0.013	-9999	-10000	0	0
PAWR	0.013	0.031	-9999	-0.58	1	1
PRKDC	0.017	0.008	-9999	-10000	0	0
PA2G4	0.019	0.016	-9999	-10000	0	0
UBE2I	0.016	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.11	0.18	-9999	-0.34	128	128
RPS6KA3	0.012	0.014	-9999	-10000	0	0
T-DHT/AR/ARA70	-0.12	0.19	-9999	-0.38	128	128
LATS2	0.017	0.034	-9999	-0.58	1	1
T-DHT/AR/PRX1	-0.11	0.18	-9999	-0.34	128	128
Cyclin D3/CDK11 p58	0.012	0.003	-9999	-10000	0	0
VAV3	0.001	0.083	-9999	-0.54	8	8
KLK2	-0.092	0.13	-9999	-0.48	17	17
CASP8	0.016	0.004	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.12	0.2	-9999	-0.36	138	138
TMPRSS2	-0.22	0.43	-9999	-1	70	70
CCND1	-0.013	0.12	-9999	-0.54	18	18
PIAS1	0.011	0.021	-9999	-10000	0	0
mol:T-DHT	-0.007	0.026	-9999	-0.072	31	31
CDC2L1	0	0.001	-9999	-10000	0	0
PIAS4	0.008	0.033	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.13	0.2	-9999	-0.39	134	134
CMTM2	0.012	0.048	-9999	-0.51	3	3
SNURF	-0.033	0.16	-9999	-0.58	28	28
ZMIZ1	0.011	0.022	-9999	-10000	0	0
CCND3	0.016	0.001	-9999	-10000	0	0
TGIF1	0.019	0.013	-9999	-10000	0	0
FKBP4	0.013	0.013	-9999	-10000	0	0

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.027	0.13	-9999	-0.34	55	55
EPHB2	-0.018	0.13	-9999	-0.51	23	23
Syndecan-2/TACI	-0.033	0.14	-9999	-0.35	56	56
LAMA1	-0.087	0.21	-9999	-0.52	68	68
Syndecan-2/alpha2 ITGB1	-0.03	0.15	-9999	-0.33	50	50
HRAS	0.016	0	-9999	-10000	0	0
Syndecan-2/CASK	-0.007	0.092	-9999	-0.35	24	24
ITGA5	-0.008	0.12	-9999	-0.58	14	14
BAX	0.021	0.089	-9999	-10000	0	0
EPB41	0.016	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	0.004	0.084	-9999	-0.31	24	24
LAMA3	-0.077	0.21	-9999	-0.54	59	59
EZR	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	0.011	0.054	-9999	-0.58	3	3
Syndecan-2/MMP2	-0.028	0.16	-9999	-0.42	45	45
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	0.018	0.046	-9999	-0.37	5	5
dendrite morphogenesis	-0.017	0.12	-9999	-0.32	47	47
Syndecan-2/GM-CSF	-0.054	0.15	-9999	-0.32	84	84
determination of left/right symmetry	-0.006	0.11	-9999	-0.41	24	24
Syndecan-2/PKC delta	0.004	0.093	-9999	-0.34	24	24
GNB2L1	0.016	0	-9999	-10000	0	0
MAPK3	-0.038	0.14	-9999	-0.28	84	84
MAPK1	-0.038	0.14	-9999	-0.28	84	84
Syndecan-2/RACK1	0.014	0.08	-9999	-0.28	24	24
NF1	0.016	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	-0.006	0.11	-9999	-0.41	24	24
ITGA2	0.008	0.063	-9999	-0.52	5	5
MAPK8	0.011	0.099	-9999	-0.34	27	27
Syndecan-2/alpha2/beta1 Integrin	-0.035	0.14	-9999	-0.33	38	38
Syndecan-2/Kininogen	-0.007	0.092	-9999	-0.35	24	24
ITGB1	0.016	0	-9999	-10000	0	0
SRC	0.022	0.076	-9999	-0.26	24	24
Syndecan-2/CASK/Protein 4.1	0.004	0.084	-9999	-0.31	24	24
extracellular matrix organization	0.004	0.092	-9999	-0.34	24	24
actin cytoskeleton reorganization	-0.027	0.13	-9999	-0.33	55	55
Syndecan-2/Caveolin-2/Ras	0.011	0.093	-9999	-0.31	26	26
Syndecan-2/Laminin alpha3	-0.053	0.16	-9999	-0.36	76	76
Syndecan-2/RasGAP	0.021	0.077	-9999	-0.26	24	24
alpha5/beta1 Integrin	0.006	0.085	-9999	-0.41	14	14
PRKCD	0.016	0	-9999	-10000	0	0
Syndecan-2 dimer	-0.017	0.12	-9999	-0.32	47	47
GO:0007205	0.004	0.001	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.031	0.075	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
SDCBP	0.016	0	-9999	-10000	0	0
TNFRSF13B	-0.043	0.17	-9999	-0.57	34	34
RASA1	0.016	0	-9999	-10000	0	0
alpha2/beta1 Integrin	0.018	0.046	-9999	-0.37	5	5
Syndecan-2/Synbindin	0.004	0.093	-9999	-0.34	24	24
TGFB1	0.016	0	-9999	-10000	0	0
CASP3	0.015	0.085	-9999	-0.3	24	24
FN1	-0.035	0.16	-9999	-0.53	33	33
Syndecan-2/IL8	-0.049	0.16	-9999	-0.37	70	70
SDC2	-0.006	0.11	-9999	-0.41	24	24
KNG1	0	0	-9999	-10000	0	0
Syndecan-2/Neurofibromin	0.004	0.093	-9999	-0.34	24	24
TRAPPC4	0.016	0	-9999	-10000	0	0
CSF2	-0.078	0.2	-9999	-0.51	63	63
Syndecan-2/TGFB1	0.004	0.093	-9999	-0.34	24	24
Syndecan-2/Syntenin/PI-4-5-P2	0.004	0.084	-9999	-0.31	24	24
Syndecan-2/Ezrin	0.014	0.085	-9999	-0.3	24	24
PRKACA	0.015	0.085	-9999	-0.3	24	24
angiogenesis	-0.048	0.16	-9999	-0.36	70	70
MMP2	-0.037	0.17	-9999	-0.58	32	32
IL8	-0.069	0.21	-9999	-0.57	51	51
calcineurin-NFAT signaling pathway	-0.033	0.14	-9999	-0.35	56	56

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.001	0.093	-9999	-0.58	9	9
mol:S1P	0.001	0.004	-9999	-10000	0	0
S1P1/S1P/Gi	-0.099	0.19	-9999	-0.31	141	141
GNAO1	-0.17	0.27	-9999	-0.58	110	110
S1P/S1P3/G12/G13	0.025	0.051	-9999	-0.31	8	8
AKT1	-0.035	0.16	-9999	-0.84	9	9
AKT3	-0.056	0.25	-9999	-1.3	11	11
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.001	0.093	-9999	-0.57	9	9
GNAI2	0.017	0.004	-9999	-10000	0	0
GNAI3	0.017	0.003	-9999	-10000	0	0
GNAI1	0.012	0.054	-9999	-0.57	3	3
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.004	0.087	-9999	-0.57	8	8
S1PR2	0.016	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	-0.1	0.22	-9999	-0.52	56	56
MAPK3	-0.089	0.21	-9999	-0.49	56	56
MAPK1	-0.089	0.21	-9999	-0.49	56	56
JAK2	-0.088	0.21	-9999	-0.5	57	57
CXCR4	-0.093	0.22	-9999	-0.5	57	57
FLT1	0.018	0.003	-9999	-10000	0	0
RhoA/GDP	0.012	0	-9999	-10000	0	0
Rac1/GDP	0.012	0	-9999	-10000	0	0
SRC	-0.089	0.21	-9999	-0.49	56	56
S1P/S1P3/Gi	-0.1	0.22	-9999	-0.52	56	56
RAC1	0.016	0	-9999	-10000	0	0
RhoA/GTP	-0.087	0.2	-9999	-0.47	56	56
VEGFA	0.018	0.003	-9999	-10000	0	0
S1P/S1P2/Gi	-0.095	0.19	-9999	-0.34	111	111
VEGFR1 homodimer/VEGFA homodimer	0.032	0.008	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.011	0.11	-9999	-0.26	58	58
GNAQ	0.016	0	-9999	-10000	0	0
GNAZ	-0.11	0.24	-9999	-0.58	76	76
G12/G13	0.023	0	-9999	-10000	0	0
GNA14	-0.067	0.2	-9999	-0.58	50	50
GNA15	0.012	0.044	-9999	-0.58	2	2
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
GNA11	0.014	0.031	-9999	-0.58	1	1
Rac1/GTP	-0.087	0.2	-9999	-0.47	56	56

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	-0.013	0.076	-9999	-10000	0	0
BIRC5	-0.36	0.23	-9999	-0.51	259	259
NFKBIA	-0.012	0.077	-9999	-10000	0	0
CPEB1	-0.28	0.29	-9999	-0.58	173	173
AKT1	-0.012	0.077	-9999	-10000	0	0
NDEL1	0.016	0	-9999	-10000	0	0
Aurora A/BRCA1	-0.02	0.067	-9999	-0.4	1	1
NDEL1/TACC3	-0.021	0.1	-9999	-0.37	11	11
GADD45A	0.016	0	-9999	-10000	0	0
GSK3B	0.018	0.004	-9999	-10000	0	0
PAK1/Aurora A	-0.014	0.08	-9999	-0.48	1	1
MDM2	-0.002	0.094	-9999	-0.51	12	12
JUB	0.011	0.048	-9999	-0.51	3	3
TPX2	-0.18	0.19	-9999	-0.36	192	192
TP53	0.001	0.055	-9999	-10000	0	0
DLG7	-0.023	0.076	-9999	-10000	0	0
AURKAIP1	0.014	0.028	-9999	-0.51	1	1
ARHGEF7	0.016	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	-0.023	0.11	-9999	-0.39	11	11
G2/M transition of mitotic cell cycle	-0.02	0.067	-9999	-0.4	1	1
AURKA	-0.026	0.095	-9999	-10000	0	0
AURKB	-0.048	0.059	-9999	-10000	0	0
CDC25B	-0.006	0.07	-9999	-0.24	6	6
G2/M transition checkpoint	-0.021	0.071	-9999	-0.35	3	3
mRNA polyadenylation	-0.18	0.18	-9999	-0.36	173	173
Aurora A/CPEB	-0.18	0.19	-9999	-0.36	173	173
Aurora A/TACC1/TRAP/chTOG	0.007	0.069	-9999	-0.41	1	1
BRCA1	0.014	0.028	-9999	-0.51	1	1
centrosome duplication	-0.014	0.079	-9999	-0.47	1	1
regulation of centrosome cycle	-0.031	0.095	-9999	-0.36	11	11
spindle assembly	0.006	0.068	-9999	-0.4	1	1
TDRD7	0.016	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.19	0.14	-9999	-0.35	101	101
CENPA	-0.048	0.06	-9999	-10000	0	0
Aurora A/PP2A	-0.013	0.076	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.005	0.059	-9999	-10000	0	0
negative regulation of DNA binding	0.001	0.055	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0.023	0	-9999	-10000	0	0
RASA1	0.016	0	-9999	-10000	0	0
Ajuba/Aurora A	-0.021	0.071	-9999	-0.35	3	3
mitotic prometaphase	0.012	0.015	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.026	0.094	-9999	-10000	0	0
TACC1	0.012	0.044	-9999	-0.58	2	2
TACC3	-0.024	0.14	-9999	-0.51	27	27
Aurora A/Antizyme1	-0.002	0.07	-9999	-10000	0	0
Aurora A/RasGAP	-0.013	0.076	-9999	-10000	0	0
OAZ1	0.016	0	-9999	-10000	0	0
RAN	0.016	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.018	0.004	-9999	-10000	0	0
GIT1	0.016	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0.031	0.02	-9999	-0.34	1	1
Importin alpha/Importin beta/TPX2	-0.18	0.19	-9999	-0.36	192	192
PPP2R5D	0.016	0	-9999	-10000	0	0
Aurora A/TPX2	-0.16	0.19	-9999	-0.32	192	192
PAK1	0.014	0.031	-9999	-0.58	1	1
CKAP5	0.016	0	-9999	-10000	0	0

×

Angiopoietin receptor Tie2-mediated signaling

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
AKT1	0.025	0.28	-10000	0	-0.81	34	34
NCK1/PAK1/Dok-R	-0.042	0.12	-10000	0	-0.41	34	34
NCK1/Dok-R	-0.02	0.33	-10000	0	-1	34	34
PIK3CA	0.015	0.001	-10000	0	-10000	0	0
mol:beta2-estradiol	0.008	0.071	0.24	29	-10000	0	29
RELA	0.016	0	-10000	0	-10000	0	0
SHC1	0.015	0.028	-10000	0	-0.5	1	1
Rac/GDP	0.012	0	-10000	0	-10000	0	0
F2	-0.023	0.16	0.26	28	-0.54	25	53
TNIP2	0.016	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.088	0.28	-10000	0	-0.94	34	34
FN1	-0.035	0.16	-10000	0	-0.53	33	33
PLD2	-0.017	0.34	-10000	0	-1	34	34
PTPN11	0.016	0	-10000	0	-10000	0	0
GRB14	-0.048	0.17	-10000	0	-0.51	43	43
ELK1	0.001	0.3	-10000	0	-0.93	34	34
GRB7	-0.013	0.12	-10000	0	-0.52	19	19
PAK1	0.014	0.031	-10000	0	-0.58	1	1
Tie2/Ang1/alpha5/beta1 Integrin	-0.12	0.31	-10000	0	-1	34	34
CDKN1A	0.031	0.2	-10000	0	-0.58	24	24
ITGA5	-0.008	0.12	-10000	0	-0.58	14	14
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.02	0.33	-10000	0	-1	34	34
CRK	0.016	0	-10000	0	-10000	0	0
mol:NO	0.044	0.22	-10000	0	-0.61	34	34
PLG	-0.027	0.34	-10000	0	-1.1	34	34
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.005	0.27	-10000	0	-0.81	34	34
GRB2	0.016	0	-10000	0	-10000	0	0
PIK3R1	0.016	0.001	-10000	0	-10000	0	0
ANGPT2	-0.041	0.2	-10000	0	-0.66	18	18
BMX	-0.11	0.36	-10000	0	-1.1	34	34
ANGPT1	-0.055	0.37	-10000	0	-1.3	29	29
tube development	0.021	0.22	-10000	0	-0.61	31	31
ANGPT4	0.002	0.067	-10000	0	-0.5	6	6
response to hypoxia	-0.001	0.021	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.053	0.35	-10000	0	-1.1	34	34
alpha5/beta1 Integrin	0.006	0.085	-10000	0	-0.41	14	14
FGF2	-0.18	0.28	-10000	0	-0.58	116	116
STAT5A (dimer)	0.023	0.24	-10000	0	-0.7	28	28
mol:L-citrulline	0.044	0.22	-10000	0	-0.61	34	34
AGTR1	-0.23	0.29	-10000	0	-0.57	151	151
MAPK14	-0.014	0.33	-10000	0	-1	34	34
Tie2/SHP2	-0.034	0.15	-10000	0	-1.1	6	6
TEK	0.017	0.18	-10000	0	-1.2	6	6
RPS6KB1	0.023	0.27	-10000	0	-0.79	34	34
Angiotensin II/AT1	-0.17	0.22	-10000	0	-0.42	151	151
Tie2/Ang1/GRB2	-0.021	0.34	-10000	0	-1.1	34	34
MAPK3	-0.005	0.31	-10000	0	-0.96	34	34
MAPK1	-0.005	0.31	-10000	0	-0.96	34	34
Tie2/Ang1/GRB7	-0.036	0.35	-10000	0	-1.1	34	34
NFKB1	0.016	0	-10000	0	-10000	0	0
MAPK8	-0.019	0.34	-10000	0	-1	34	34
PI3K	0.006	0.31	-10000	0	-0.93	34	34
FES	-0.015	0.32	-10000	0	-1	34	34
Crk/Dok-R	-0.02	0.33	-10000	0	-1	34	34
Tie2/Ang1/ABIN2	-0.021	0.34	-10000	0	-1.1	34	34
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.032	0.25	-10000	0	-0.73	34	34
STAT5A	0.014	0.031	-10000	0	-0.58	1	1
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.023	0.27	-10000	0	-0.79	34	34
Tie2/Ang2	0.003	0.27	-10000	0	-0.83	27	27
Tie2/Ang1	-0.028	0.36	-10000	0	-1.1	34	34
FOXO1	0.04	0.25	-10000	0	-0.73	34	34
ELF1	0.025	0.014	-10000	0	-10000	0	0
ELF2	-0.019	0.33	-10000	0	-1	34	34
mol:Choline	-0.013	0.32	-10000	0	-1	34	34
cell migration	-0.028	0.07	-10000	0	-0.23	34	34
FYN	0.016	0.24	-10000	0	-0.71	28	28
DOK2	-0.007	0.11	-10000	0	-0.57	14	14
negative regulation of cell cycle	0.033	0.19	-10000	0	-0.52	25	25
ETS1	0.008	0.067	-10000	0	-0.24	4	4
PXN	0.038	0.23	-10000	0	-0.66	34	34
ITGB1	0.016	0	-10000	0	-10000	0	0
NOS3	0.039	0.24	-10000	0	-0.69	34	34
RAC1	0.016	0	-10000	0	-10000	0	0
TNF	-0.016	0.13	-10000	0	-0.45	21	21
MAPKKK cascade	-0.013	0.32	-10000	0	-1	34	34
RASA1	0.016	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.02	0.34	-10000	0	-1.1	34	34
NCK1	0.016	0	-10000	0	-10000	0	0
vasculogenesis	0.048	0.2	-10000	0	-0.55	34	34
mol:Phosphatidic acid	-0.013	0.32	-10000	0	-1	34	34
mol:Angiotensin II	0.002	0.001	-10000	0	-10000	0	0
mol:NADP	0.044	0.22	-10000	0	-0.61	34	34
Rac1/GTP	-0.071	0.22	-10000	0	-0.74	34	34
MMP2	-0.043	0.36	-10000	0	-1.1	34	34

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.016	0	-9999	-10000	0	0
VLDLR	-0.001	0.098	-9999	-0.58	10	10
LRPAP1	0.014	0.028	-9999	-0.51	1	1
NUDC	0.016	0	-9999	-10000	0	0
RELN/LRP8	-0.16	0.22	-9999	-0.4	141	141
CaM/Ca2+	0.012	0	-9999	-10000	0	0
KATNA1	0.016	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.14	0.2	-9999	-0.36	130	130
IQGAP1/CaM	0.023	0	-9999	-10000	0	0
DAB1	-0.07	0.2	-9999	-0.55	51	51
IQGAP1	0.016	0	-9999	-10000	0	0
PLA2G7	-0.052	0.18	-9999	-0.51	46	46
CALM1	0.016	0	-9999	-10000	0	0
DYNLT1	0.016	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.048	0.15	-9999	-0.36	67	67
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.016	0	-9999	-10000	0	0
CDK5R1	-0.014	0.12	-9999	-0.51	20	20
LIS1/Poliovirus Protein 3A	0.02	0	-9999	-10000	0	0
CDK5R2	-0.021	0.12	-9999	-0.51	22	22
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.17	0.22	-9999	-0.39	168	168
YWHAE	0.014	0.031	-9999	-0.58	1	1
NDEL1/14-3-3 E	-0.096	0.18	-9999	-0.44	37	37
MAP1B	-0.033	0.095	-9999	-0.31	38	38
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.12	0.2	-9999	-0.52	39	39
RELN	-0.2	0.28	-9999	-0.57	131	131
PAFAH/LIS1	-0.01	0.11	-9999	-0.29	46	46
LIS1/CLIP170	0.031	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.094	0.11	-9999	-0.36	30	30
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.11	0.18	-9999	-0.49	31	31
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.11	0.19	-9999	-0.47	38	38
LIS1/IQGAP1	0.031	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.026	0	-9999	-10000	0	0
PAFAH1B3	-0.017	0.13	-9999	-0.51	22	22
PAFAH1B2	0.016	0	-9999	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0.007	0.066	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.085	0.17	-9999	-0.44	32	32
LRP8	-0.081	0.2	-9999	-0.51	66	66
NDEL1/Katanin 60	-0.095	0.18	-9999	-0.44	37	37
P39/CDK5	-0.13	0.2	-9999	-0.51	41	41
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.031	0	-9999	-10000	0	0
CDK5	-0.12	0.19	-9999	-0.52	31	31
PPP2R5D	0.016	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.027	0	-9999	-10000	0	0
CSNK2A1	0.016	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.13	0.19	-9999	-0.56	24	24
RELN/VLDLR	-0.15	0.21	-9999	-0.56	38	38
CDC42	0	0	-9999	-10000	0	0

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.017	0.039	-9999	0	-0.35	4	4
ARNO/beta Arrestin1-2	-0.032	0.084	-9999	0	-0.37	1	1
EGFR	-0.008	0.11	-9999	0	-0.54	15	15
EPHA2	0.011	0.054	-9999	0	-0.58	3	3
USP6	0.016	0	-9999	0	-10000	0	0
IQSEC1	0.014	0.028	-9999	0	-0.51	1	1
EGFR/EGFR/EGF/EGF	-0.018	0.12	-9999	0	-0.37	37	37
ARRB2	0.011	0.015	-9999	0	-0.18	2	2
mol:GTP	0.015	0.033	-9999	0	-0.21	4	4
ARRB1	0.011	0.054	-9999	0	-0.58	3	3
FBXO8	0.016	0	-9999	0	-10000	0	0
TSHR	0.002	0.067	-9999	0	-0.51	6	6
EGF	-0.018	0.12	-9999	0	-0.51	22	22
somatostatin receptor activity	0	0	-9999	0	-0.001	59	59
ARAP2	0.012	0.044	-9999	0	-0.58	2	2
mol:GDP	-0.07	0.11	-9999	0	-0.23	85	85
mol:PI-3-4-5-P3	0	0	-9999	0	-0.001	53	53
ITGA2B	-0.026	0.14	-9999	0	-0.51	28	28
ARF6	0.015	0	-9999	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.03	0.055	-9999	0	-0.3	3	3
ADAP1	0.009	0.062	-9999	0	-0.58	4	4
KIF13B	0.016	0	-9999	0	-10000	0	0
HGF/MET	-0.081	0.18	-9999	0	-0.41	86	86
PXN	0.016	0	-9999	0	-10000	0	0
ARF6/GTP	-0.064	0.12	-9999	0	-0.26	59	59
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.005	0.1	-9999	0	-0.3	38	38
ADRB2	-0.054	0.19	-9999	0	-0.58	42	42
receptor agonist activity	0	0	-9999	0	0	68	68
actin filament binding	0	0	-9999	0	0	59	59
SRC	0.015	0	-9999	0	-10000	0	0
ITGB3	-0.054	0.19	-9999	0	-0.58	42	42
GNAQ	0.015	0	-9999	0	-10000	0	0
EFA6/PI-4-5-P2	0	0	-9999	0	-0.001	54	54
ARF6/GDP	0.008	0.095	-9999	0	-0.35	17	17
ARF6/GDP/GULP/ACAP1	-0.11	0.17	-9999	0	-0.42	65	65
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.023	0.14	-9999	0	-0.33	42	42
ACAP1	-0.017	0.13	-9999	0	-0.56	20	20
ACAP2	0.016	0	-9999	0	-10000	0	0
LHCGR/beta Arrestin2	0.003	0.022	-9999	0	-0.27	2	2
EFNA1	0.002	0.082	-9999	0	-0.51	9	9
HGF	-0.12	0.25	-9999	0	-0.57	85	85
CYTH3	0.013	0	-9999	0	-10000	0	0
CYTH2	0.01	0.002	-9999	0	-10000	0	0
NCK1	0.016	0	-9999	0	-10000	0	0
fibronectin binding	0	0	-9999	0	0	45	45
endosomal lumen acidification	0	0	0	3	0	53	56
microtubule-based process	0	0	-9999	0	-10000	0	0
GULP1	-0.076	0.21	-9999	0	-0.58	55	55
GNAQ/ARNO	0.017	0.007	-9999	0	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	0	-10000	0	0
PIP3-E	0	0	-9999	0	0	4	4
MET	0.014	0.028	-9999	0	-0.51	1	1
GNA14	-0.067	0.2	-9999	0	-0.58	50	50
GNA15	0.012	0.044	-9999	0	-0.58	2	2
GIT1	0.016	0	-9999	0	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	0	-0.001	55	55
GNA11	0.014	0.031	-9999	0	-0.58	1	1
LHCGR	0.001	0.039	-9999	0	-0.51	2	2
AGTR1	-0.24	0.29	-9999	0	-0.58	151	151
desensitization of G-protein coupled receptor protein signaling pathway	0.003	0.022	-9999	0	-0.27	2	2
IPCEF1/ARNO	-0.003	0.077	-9999	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.057	0.17	-9999	0	-0.41	66	66

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	0.024	0.15	0.57	24	-10000	0	24
PI3K Class IB/PDE3B	-0.024	0.15	-10000	0	-0.57	24	24
PDE3B	-0.024	0.15	-10000	0	-0.58	24	24

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.042	0.15	0.42	45	-10000	0	45
KIRREL	-0.052	0.19	-10000	0	-0.59	39	39
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.042	0.15	-10000	0	-0.42	45	45
PLCG1	0.016	0	-10000	0	-10000	0	0
ARRB2	0.016	0	-10000	0	-10000	0	0
WASL	0.016	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.05	0.12	-10000	0	-0.33	39	39
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.007	0.1	-10000	0	-0.4	6	6
FYN	-0.03	0.12	-10000	0	-0.33	40	40
mol:Ca2+	-0.049	0.12	-10000	0	-0.33	39	39
mol:DAG	-0.05	0.12	-10000	0	-0.33	39	39
NPHS2	-0.025	0.11	-10000	0	-0.51	18	18
mol:IP3	-0.05	0.12	-10000	0	-0.33	39	39
regulation of endocytosis	-0.019	0.12	-10000	0	-0.34	21	21
Nephrin/NEPH1/podocin/Cholesterol	-0.041	0.12	-10000	0	-0.31	59	59
establishment of cell polarity	-0.042	0.15	-10000	0	-0.42	45	45
Nephrin/NEPH1/podocin/NCK1-2	-0.014	0.12	-10000	0	-0.46	6	6
Nephrin/NEPH1/beta Arrestin2	-0.018	0.12	-10000	0	-0.34	21	21
NPHS1	-0.009	0.068	-10000	0	-0.5	6	6
Nephrin/NEPH1/podocin	-0.03	0.12	-10000	0	-0.33	40	40
TJP1	0.016	0	-10000	0	-10000	0	0
NCK1	0.016	0	-10000	0	-10000	0	0
NCK2	0.016	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.05	0.12	-10000	0	-0.33	39	39
CD2AP	0.016	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.05	0.12	-10000	0	-0.33	39	39
GRB2	0.016	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.026	0.12	-10000	0	-0.32	40	40
cytoskeleton organization	-0.007	0.12	-10000	0	-0.47	6	6
Nephrin/NEPH1	-0.027	0.1	-10000	0	-0.3	45	45
Nephrin/NEPH1/ZO-1	-0.042	0.11	-10000	0	-0.34	39	39

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.004	0.11	-9999	-0.54	11	11
Syndecan-4/Syndesmos	-0.03	0.13	-9999	-0.56	10	10
positive regulation of JNK cascade	-0.1	0.18	-9999	-0.49	36	36
Syndecan-4/ADAM12	-0.056	0.16	-9999	-0.43	34	34
CCL5	-0.03	0.16	-9999	-0.55	29	29
Rac1/GDP	0.012	0	-9999	-10000	0	0
DNM2	0.016	0	-9999	-10000	0	0
ITGA5	-0.008	0.12	-9999	-0.58	14	14
SDCBP	0.016	0	-9999	-10000	0	0
PLG	-0.003	0.061	-9999	-0.51	5	5
ADAM12	-0.039	0.16	-9999	-0.51	37	37
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.038	0.051	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.079	0.18	-9999	-0.45	42	42
Syndecan-4/CXCL12/CXCR4	-0.11	0.19	-9999	-0.52	36	36
Syndecan-4/Laminin alpha3	-0.075	0.18	-9999	-0.44	45	45
MDK	-0.014	0.12	-9999	-0.51	20	20
Syndecan-4/FZD7	-0.045	0.14	-9999	-0.49	16	16
Syndecan-4/Midkine	-0.044	0.14	-9999	-0.5	15	15
FZD7	-0.014	0.13	-9999	-0.58	18	18
Syndecan-4/FGFR1/FGF	-0.19	0.23	-9999	-0.53	89	89
THBS1	-0.004	0.11	-9999	-0.58	12	12
integrin-mediated signaling pathway	-0.056	0.17	-9999	-0.5	27	27
positive regulation of MAPKKK cascade	-0.1	0.18	-9999	-0.49	36	36
Syndecan-4/TACI	-0.06	0.15	-9999	-0.48	20	20
CXCR4	0.007	0.07	-9999	-0.58	5	5
cell adhesion	0.004	0.11	-9999	-0.49	11	11
Syndecan-4/Dynamin	-0.03	0.13	-9999	-0.56	10	10
Syndecan-4/TSP1	-0.04	0.14	-9999	-0.57	12	12
Syndecan-4/GIPC	-0.03	0.13	-9999	-0.56	10	10
Syndecan-4/RANTES	-0.052	0.16	-9999	-0.52	22	22
ITGB1	0.016	0	-9999	-10000	0	0
LAMA1	-0.087	0.21	-9999	-0.52	68	68
LAMA3	-0.077	0.21	-9999	-0.54	59	59
RAC1	0.016	0	-9999	-10000	0	0
PRKCA	0.02	0.061	-9999	-0.52	3	3
Syndecan-4/alpha-Actinin	-0.03	0.13	-9999	-0.56	10	10
TFPI	0.002	0.088	-9999	-0.58	8	8
F2	-0.035	0.14	-9999	-0.51	29	29
alpha5/beta1 Integrin	0.006	0.085	-9999	-0.41	14	14
positive regulation of cell adhesion	-0.11	0.2	-9999	-0.5	43	43
ACTN1	0.016	0	-9999	-10000	0	0
TNC	-0.043	0.17	-9999	-0.56	36	36
Syndecan-4/CXCL12	-0.12	0.19	-9999	-0.53	35	35
FGF6	0	0.002	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
CXCL12	-0.16	0.27	-9999	-0.58	105	105
TNFRSF13B	-0.043	0.17	-9999	-0.57	34	34
FGF2	-0.18	0.28	-9999	-0.58	116	116
FGFR1	-0.12	0.25	-9999	-0.58	83	83
Syndecan-4/PI-4-5-P2	-0.04	0.13	-9999	-0.56	10	10
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.034	0.16	-9999	-0.53	33	33
cell migration	-0.015	0.022	-9999	-10000	0	0
PRKCD	0.016	0.008	-9999	-10000	0	0
vasculogenesis	-0.039	0.14	-9999	-0.55	12	12
SDC4	-0.041	0.14	-9999	-0.6	10	10
Syndecan-4/Tenascin C	-0.058	0.17	-9999	-0.52	27	27
Syndecan-4/PI-4-5-P2/PKC alpha	-0.03	0.04	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.03	0.13	-9999	-0.56	10	10
MMP9	-0.13	0.24	-9999	-0.51	97	97
Rac1/GTP	0.003	0.11	-9999	-0.51	11	11
cytoskeleton organization	-0.029	0.13	-9999	-0.53	10	10
GIPC1	0.016	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.036	0.15	-9999	-0.6	13	13

×

FAS signaling pathway (CD95)

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
SPTAN1	0.012	0.05	0.24	16	-10000	0	16
RFC1	0.012	0.05	0.24	14	-10000	0	14
PRKDC	0.012	0.05	0.24	16	-10000	0	16
RIPK1	0.019	0.005	-10000	0	-10000	0	0
CASP7	-0.029	0.044	0.25	2	-10000	0	2
FASLG/FAS/FADD/FAF1	-0.038	0.086	0.22	5	-0.31	22	27
MAP2K4	-0.088	0.17	-10000	0	-0.44	21	21
mol:ceramide	-0.056	0.13	-10000	0	-0.39	28	28
GSN	0.006	0.065	0.24	14	-0.34	5	19
FASLG/FAS/FADD/FAF1/Caspase 8	-0.035	0.11	-10000	0	-0.36	22	22
FAS	0.001	0.071	-10000	0	-0.59	5	5
BID	0.003	0.034	0.3	3	-0.31	1	4
MAP3K1	-0.037	0.1	-10000	0	-0.26	12	12
MAP3K7	0.009	0.008	-10000	0	-10000	0	0
RB1	0.012	0.05	0.24	14	-10000	0	14
CFLAR	0.019	0.005	-10000	0	-10000	0	0
HGF/MET	-0.066	0.17	-10000	0	-0.35	92	92
ARHGDIB	0.012	0.05	0.24	16	-10000	0	16
FADD	0	0.068	-10000	0	-0.52	6	6
actin filament polymerization	-0.006	0.065	0.34	5	-0.24	14	19
NFKB1	-0.096	0.1	-10000	0	-0.27	19	19
MAPK8	-0.16	0.25	-10000	0	-0.42	162	162
DFFA	0.012	0.05	0.24	16	-10000	0	16
DNA fragmentation during apoptosis	0.012	0.05	0.24	14	-10000	0	14
FAS/FADD/MET	0.007	0.064	-10000	0	-0.32	12	12
CFLAR/RIP1	0.012	0.011	-10000	0	-10000	0	0
FAIM3	0.009	0.072	-10000	0	-0.54	6	6
FAF1	0.009	0.009	-10000	0	-10000	0	0
PARP1	0.012	0.05	0.24	14	-10000	0	14
DFFB	0.012	0.05	0.24	14	-10000	0	14
CHUK	-0.083	0.09	-10000	0	-0.27	1	1
FASLG	-0.037	0.16	-10000	0	-0.57	28	28
FAS/FADD	0.001	0.072	-10000	0	-0.4	11	11
HGF	-0.12	0.25	-10000	0	-0.57	85	85
LMNA	0.011	0.047	0.22	14	-10000	0	14
CASP6	0.012	0.05	0.24	14	-10000	0	14
CASP10	0.009	0.008	-10000	0	-10000	0	0
CASP3	0.014	0.059	0.27	17	-10000	0	17
PTPN13	0.002	0.088	-10000	0	-0.58	8	8
CASP8	0.005	0.04	0.39	3	-10000	0	3
IL6	-0.57	0.67	-10000	0	-1.3	162	162
MET	0.014	0.028	-10000	0	-0.51	1	1
ICAD/CAD	0.011	0.047	0.23	14	-10000	0	14
FASLG/FAS/FADD/FAF1/Caspase 10	-0.057	0.14	-10000	0	-0.39	28	28
activation of caspase activity by cytochrome c	0.003	0.034	0.3	3	-0.31	1	4
PAK2	0.012	0.05	0.24	16	-10000	0	16
BCL2	-0.007	0.12	-10000	0	-0.57	14	14

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.04	0.14	-9999	-0.54	13	13
FZD6	0.016	0	-9999	-10000	0	0
WNT6	-0.057	0.18	-9999	-0.53	48	48
WNT4	-0.029	0.15	-9999	-0.57	27	27
FZD3	0.012	0.044	-9999	-0.58	2	2
WNT5A	-0.008	0.11	-9999	-0.54	15	15
WNT11	-0.058	0.19	-9999	-0.53	48	48

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.004	0.033	-10000	0	-10000	0	0
HDAC1	0.014	0.012	-10000	0	-10000	0	0
AES	0.015	0.004	-10000	0	-10000	0	0
FBXW11	0.016	0	-10000	0	-10000	0	0
DTX1	-0.007	0.11	-10000	0	-0.56	14	14
LRP6/FZD1	0.022	0.023	-10000	0	-0.42	1	1
TLE1	0.01	0.054	-10000	0	-0.58	3	3
AP1	-0.091	0.18	-10000	0	-0.32	121	121
NCSTN	0.016	0	-10000	0	-10000	0	0
ADAM10	0.015	0	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.031	0.075	-10000	0	-10000	0	0
NICD/RBPSUH	0.038	0.009	-10000	0	-10000	0	0
WIF1	-0.12	0.24	-10000	0	-0.57	80	80
NOTCH1	0	0	-10000	0	-10000	0	0
PSENEN	0.016	0	-10000	0	-10000	0	0
KREMEN2	-0.18	0.25	-10000	0	-0.51	134	134
DKK1	-0.083	0.22	-10000	0	-0.56	61	61
beta catenin/beta TrCP1	0.032	0.045	-10000	0	-10000	0	0
APH1B	0.016	0	-10000	0	-10000	0	0
APH1A	0.016	0	-10000	0	-10000	0	0
AXIN1	0.005	0.015	-10000	0	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	0.031	0.052	0.28	4	-10000	0	4
PSEN1	0.016	0	-10000	0	-10000	0	0
FOS	-0.17	0.27	-10000	0	-0.58	110	110
JUN	-0.006	0.11	-10000	0	-0.58	13	13
MAP3K7	0.015	0.005	-10000	0	-10000	0	0
CTNNB1	0.024	0.048	0.2	12	-10000	0	12
MAPK3	0.016	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.16	0.21	-10000	0	-0.35	179	179
HNF1A	0.009	0.055	-10000	0	-0.51	4	4
CTBP1	0.014	0.028	-10000	0	-0.5	1	1
MYC	-0.047	0.32	-10000	0	-1.4	18	18
NKD1	-0.02	0.14	-10000	0	-0.56	22	22
FZD1	0.014	0.031	-10000	0	-0.58	1	1
NOTCH1 precursor/Deltex homolog 1	0.026	0.058	-10000	0	-10000	0	0
apoptosis	-0.09	0.18	-10000	0	-0.32	121	121
Delta 1/NOTCHprecursor	0.033	0.039	-10000	0	-10000	0	0
DLL1	0.006	0.073	-10000	0	-0.55	6	6
PPARD	0.022	0.027	-10000	0	-10000	0	0
Gamma Secretase	0.044	0.011	-10000	0	-10000	0	0
APC	0.005	0.015	-10000	0	-10000	0	0
DVL1	0.01	0.032	-10000	0	-10000	0	0
CSNK2A1	0.016	0.002	-10000	0	-10000	0	0
MAP3K7IP1	-0.001	0.005	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.15	0.2	-10000	0	-0.35	170	170
LRP6	0.016	0	-10000	0	-10000	0	0
CSNK1A1	0.016	0.002	-10000	0	-10000	0	0
NLK	0.018	0.012	-10000	0	-10000	0	0
CCND1	-0.014	0.22	-10000	0	-1.5	7	7
WNT1	0.007	0.048	-10000	0	-0.51	3	3
Axin1/APC/beta catenin	0.043	0.033	-10000	0	-10000	0	0
DKK2	-0.1	0.22	-10000	0	-0.51	82	82
NOTCH1 precursor/DVL1	0.002	0.01	-10000	0	-10000	0	0
GSK3B	0.015	0.001	-10000	0	-10000	0	0
FRAT1	0.015	0.002	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.01	0.05	-10000	0	-10000	0	0
PPP2R5D	0.013	0.069	0.28	22	-10000	0	22
MAPK1	0.016	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.047	0.14	-10000	0	-0.31	73	73
RBPJ	0.016	0	-10000	0	-10000	0	0
CREBBP	0.018	0.006	-10000	0	-10000	0	0

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.016	0	-9999	-10000	0	0
GNAT1/GTP	0.003	0.04	-9999	-0.37	4	4
Metarhodopsin II/Arrestin	0.002	0.004	-9999	-10000	0	0
PDE6G/GNAT1/GTP	0.003	0.067	-9999	-0.3	16	16
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.004	0.055	-9999	-0.51	4	4
GRK1	0.001	0.004	-9999	-10000	0	0
CNG Channel	-0.15	0.16	-9999	-0.48	39	39
mol:Na +	-0.16	0.16	-9999	-0.48	44	44
mol:ADP	0.001	0.004	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.065	0.17	-9999	-0.35	89	89
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.16	0.16	-9999	-0.49	44	44
CNGB1	-0.21	0.26	-9999	-0.51	154	154
RDH5	0.014	0.031	-9999	-0.58	1	1
SAG	0	0	-9999	-10000	0	0
mol:Ca2+	-0.13	0.17	-9999	-0.46	44	44
Na + (4 Units)	-0.15	0.15	-9999	-0.45	44	44
RGS9	-0.11	0.24	-9999	-0.58	76	76
GNB1/GNGT1	0.001	0.085	-9999	-0.36	19	19
GNAT1/GDP	-0.052	0.15	-9999	-0.3	86	86
GUCY2D	-0.049	0.17	-9999	-0.51	42	42
GNGT1	-0.014	0.12	-9999	-0.51	19	19
GUCY2F	0.002	0.005	-9999	-10000	0	0
GNB5	0.016	0	-9999	-10000	0	0
mol:GMP (4 units)	0.003	0.095	-9999	-0.32	16	16
mol:11-cis-retinal	0.014	0.031	-9999	-0.57	1	1
mol:cGMP	-0.022	0.11	-9999	-0.45	4	4
GNB1	0.016	0	-9999	-10000	0	0
Rhodopsin	0.013	0.024	-9999	-0.42	1	1
SLC24A1	0.016	0	-9999	-10000	0	0
CNGA1	-0.053	0.18	-9999	-0.54	44	44
Metarhodopsin II	0.003	0.005	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.024	0.12	-9999	-0.48	4	4
RGS9BP	-0.011	0.12	-9999	-0.56	16	16
Metarhodopsin II/Transducin	0.01	0.036	-9999	-10000	0	0
GCAP Family/Ca ++	0.002	0.07	-9999	-0.29	19	19
PDE6A/B	-0.002	0.1	-9999	-0.42	20	20
mol:Pi	-0.065	0.17	-9999	-0.35	89	89
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	0.006	0.071	-9999	-0.26	23	23
PDE6B	-0.011	0.12	-9999	-0.57	16	16
PDE6A	0.007	0.061	-9999	-0.51	5	5
PDE6G	-0.002	0.094	-9999	-0.51	12	12
RHO	0.004	0.007	-9999	-10000	0	0
PDE6	-0.089	0.15	-9999	-0.58	13	13
GUCA1A	-0.013	0.11	-9999	-0.51	17	17
GC2/GCAP Family	0.003	0.071	-9999	-0.29	19	19
GUCA1C	0	0.027	-9999	-0.51	1	1
GUCA1B	0.012	0.042	-9999	-0.54	2	2

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.013	0.033	-10000	0	-10000	0	0
AES	0.019	0.025	-10000	0	-10000	0	0
FBXW11	0.016	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.02	0.024	-10000	0	-0.41	1	1
SMAD4	0.016	0	-10000	0	-10000	0	0
DKK2	-0.1	0.22	-10000	0	-0.51	82	82
TLE1	0.014	0.06	-10000	0	-0.58	3	3
MACF1	0.016	0	-10000	0	-10000	0	0
CTNNB1	0.04	0.08	0.26	8	-10000	0	8
WIF1	-0.12	0.24	-10000	0	-0.57	80	80
beta catenin/RanBP3	0.037	0.13	0.37	44	-10000	0	44
KREMEN2	-0.18	0.25	-10000	0	-0.51	134	134
DKK1	-0.083	0.22	-10000	0	-0.56	61	61
beta catenin/beta TrCP1	0.048	0.075	0.25	8	-10000	0	8
FZD1	0.014	0.031	-10000	0	-0.58	1	1
AXIN2	-0.086	0.36	-10000	0	-1.4	24	24
AXIN1	0.016	0.001	-10000	0	-10000	0	0
RAN	0.016	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.019	0.035	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.083	0.059	-10000	0	-10000	0	0
Axin1/APC/GSK3	0.017	0.046	0.2	10	-10000	0	10
Axin1/APC/GSK3/beta catenin/Macf1	0.062	0.036	-10000	0	-10000	0	0
HNF1A	0.014	0.062	-10000	0	-0.51	4	4
CTBP1	0.018	0.038	-10000	0	-0.48	1	1
MYC	-0.073	0.34	-10000	0	-1.5	18	18
RANBP3	0.016	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.16	0.2	-10000	0	-0.35	179	179
NKD1	-0.021	0.14	-10000	0	-0.56	22	22
TCF4	0.015	0.06	-10000	0	-0.56	3	3
TCF3	0.019	0.027	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0.028	0.035	-10000	0	-0.31	1	1
Ran/GTP	0.012	0.002	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.058	0.17	0.48	42	-10000	0	42
LEF1	0.012	0.067	-10000	0	-0.5	5	5
DVL1	0.059	0.038	-10000	0	-10000	0	0
CSNK2A1	0.016	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.066	0.086	-10000	0	-0.34	1	1
DKK1/LRP6/Kremen 2	-0.15	0.2	-10000	0	-0.35	170	170
LRP6	0.016	0.001	-10000	0	-10000	0	0
CSNK1A1	0.018	0.031	-10000	0	-10000	0	0
NLK	0.015	0.006	-10000	0	-10000	0	0
CCND1	-0.041	0.24	-10000	0	-1.3	9	9
WNT1	0.008	0.048	-10000	0	-0.51	3	3
GSK3A	0.016	0.001	-10000	0	-10000	0	0
GSK3B	0.016	0.001	-10000	0	-10000	0	0
FRAT1	0.015	0	-10000	0	-10000	0	0
PPP2R5D	0.048	0.071	0.31	22	-10000	0	22
APC	0.041	0.03	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.071	0.09	0.24	71	-10000	0	71
CREBBP	0.019	0.027	-10000	0	-10000	0	0

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.088	0.22	-9999	-0.58	62	62
GNB1/GNG2	-0.024	0.14	-9999	-0.5	13	13
mol:DAG	-0.014	0.13	-9999	-0.45	13	13
PLCG1	-0.015	0.13	-9999	-0.47	13	13
YES1	-0.029	0.14	-9999	-0.5	13	13
FZD3	0.012	0.044	-9999	-0.58	2	2
FZD6	0.016	0	-9999	-10000	0	0
G protein	-0.015	0.13	-9999	-0.47	13	13
MAP3K7	-0.085	0.18	-9999	-0.39	55	55
mol:Ca2+	-0.013	0.12	-9999	-0.44	13	13
mol:IP3	-0.014	0.13	-9999	-0.45	13	13
NLK	-0.003	0.008	-9999	-10000	0	0
GNB1	0.016	0	-9999	-10000	0	0
CAMK2A	-0.1	0.19	-9999	-0.42	56	56
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.04	0.14	-9999	-0.54	13	13
CSNK1A1	0.016	0	-9999	-10000	0	0
GNAS	-0.029	0.14	-9999	-0.5	13	13
GO:0007205	-0.013	0.13	-9999	-0.44	13	13
WNT6	-0.057	0.18	-9999	-0.53	48	48
WNT4	-0.029	0.15	-9999	-0.57	27	27
NFAT1/CK1 alpha	-0.055	0.16	-9999	-0.46	25	25
GNG2	0.006	0.076	-9999	-0.58	6	6
WNT5A	-0.008	0.11	-9999	-0.54	15	15
WNT11	-0.058	0.19	-9999	-0.53	48	48
CDC42	-0.019	0.13	-9999	-0.47	13	13

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.014	0.028	-9999	-0.51	1	1
SPHK1	-0.053	0.18	-9999	-0.51	47	47
GNAI2	0.016	0	-9999	-10000	0	0
mol:S1P	0.004	0.057	-9999	-0.29	1	1
GNAO1	-0.17	0.27	-9999	-0.58	110	110
mol:Sphinganine-1-P	-0.025	0.13	-9999	-0.36	48	48
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.03	0.041	-9999	-10000	0	0
GNAI3	0.016	0	-9999	-10000	0	0
G12/G13	0.023	0	-9999	-10000	0	0
S1PR3	0.002	0.086	-9999	-0.57	8	8
S1PR2	0.016	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.016	0.041	-9999	-0.25	1	1
S1PR5	-0.005	0.1	-9999	-0.52	14	14
S1PR4	0.005	0.078	-9999	-0.55	7	7
GNAI1	0.011	0.054	-9999	-0.58	3	3
S1P/S1P5/G12	0.009	0.071	-9999	-0.27	14	14
S1P/S1P3/Gq	-0.012	0.11	-9999	-0.26	58	58
S1P/S1P4/Gi	-0.1	0.19	-9999	-0.46	57	57
GNAQ	0.016	0	-9999	-10000	0	0
GNAZ	-0.11	0.24	-9999	-0.58	76	76
GNA14	-0.067	0.2	-9999	-0.58	50	50
GNA15	0.012	0.044	-9999	-0.58	2	2
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
GNA11	0.014	0.031	-9999	-0.58	1	1
ABCC1	0.013	0.039	-9999	-0.51	2	2

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.29	0.3	-9999	-0.58	183	183
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.014	0.028	-9999	-0.51	1	1
TCEB1	0.016	0	-9999	-10000	0	0
HIF1A/p53	0.035	0.015	-9999	-10000	0	0
HIF1A	0.027	0.016	-9999	-10000	0	0
COPS5	0.016	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.046	0.015	-9999	-10000	0	0
FIH (dimer)	0.016	0	-9999	-10000	0	0
CDKN2A	-0.24	0.26	-9999	-0.51	174	174
ARNT/IPAS	-0.2	0.22	-9999	-0.41	183	183
HIF1AN	0.016	0	-9999	-10000	0	0
GNB2L1	0.016	0	-9999	-10000	0	0
HIF1A/ARNT	0.035	0.015	-9999	-10000	0	0
CUL2	0.016	0	-9999	-10000	0	0
OS9	0.016	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	0.031	0.017	-9999	-0.29	1	1
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.035	0.015	-9999	-10000	0	0
PHD1-3/OS9	0.033	0.048	-9999	-0.3	7	7
HIF1A/RACK1/Elongin B/Elongin C	-0.002	0.012	-9999	-10000	0	0
VHL	0.016	0	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
HIF1A/JAB1	0.035	0.015	-9999	-10000	0	0
EGLN3	0.004	0.082	-9999	-0.58	7	7
EGLN2	0.016	0	-9999	-10000	0	0
EGLN1	0.016	0	-9999	-10000	0	0
TP53	0.016	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.044	0.008	-9999	-10000	0	0
ARNT	0.016	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.016	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.089	0.13	-9999	-0.28	8	8

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.021	0.005	-9999	-10000	0	0
RAS family/GTP	-0.021	0.12	-9999	-0.42	7	7
NFATC4	-0.025	0.12	-9999	-0.38	10	10
ERBB2IP	0.016	0.003	-9999	-10000	0	0
HSP90 (dimer)	0.016	0	-9999	-10000	0	0
mammary gland morphogenesis	-0.045	0.13	-9999	-0.46	7	7
JUN	0.004	0.084	-9999	-0.34	1	1
HRAS	0.015	0.001	-9999	-10000	0	0
DOCK7	-0.037	0.13	-9999	-0.43	7	7
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.066	0.15	-9999	-0.32	71	71
AKT1	0.012	0.003	-9999	-10000	0	0
BAD	0.022	0.003	-9999	-10000	0	0
MAPK10	-0.016	0.095	-9999	-0.29	11	11
mol:GTP	-0.001	0.002	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.047	0.14	-9999	-0.5	7	7
RAF1	-0.012	0.12	-9999	-0.41	7	7
ErbB2/ErbB3/neuregulin 2	-0.15	0.18	-9999	-0.34	163	163
STAT3	0.003	0.005	-9999	-10000	0	0
cell migration	-0.003	0.089	-9999	-0.24	11	11
mol:PI-3-4-5-P3	-0.001	0.002	-9999	-10000	0	0
cell proliferation	-0.087	0.24	-9999	-0.55	37	37
FOS	-0.12	0.27	-9999	-0.51	111	111
NRAS	0.015	0.001	-9999	-10000	0	0
mol:Ca2+	-0.045	0.13	-9999	-0.46	7	7
MAPK3	-0.053	0.18	-9999	-0.52	18	18
MAPK1	-0.053	0.18	-9999	-0.52	18	18
JAK2	-0.037	0.13	-9999	-0.43	7	7
NF2	-0.001	0.004	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.039	0.13	-9999	-0.28	71	71
NRG1	-0.12	0.24	-9999	-0.56	80	80
GRB2/SOS1	0.023	0.001	-9999	-10000	0	0
MAPK8	-0.033	0.13	-9999	-0.29	30	30
MAPK9	0.002	0.075	-9999	-0.23	1	1
ERBB2	-0.014	0.07	-9999	-0.38	13	13
ERBB3	-0.002	0.096	-9999	-0.56	10	10
SHC1	0.014	0.028	-9999	-0.51	1	1
RAC1	0.016	0	-9999	-10000	0	0
apoptosis	0.005	0.012	-9999	-10000	0	0
STAT3 (dimer)	0.022	0.006	-9999	-10000	0	0
RNF41	0.027	0.008	-9999	-10000	0	0
FRAP1	0.01	0.003	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.044	0.077	-9999	-0.3	7	7
ErbB2/ErbB2/HSP90 (dimer)	-0.011	0.057	-9999	-0.31	13	13
CHRNA1	-0.05	0.17	-9999	-0.39	36	36
myelination	-0.016	0.11	-9999	-0.36	10	10
PPP3CB	-0.034	0.12	-9999	-0.4	7	7
KRAS	0.014	0.028	-9999	-0.51	1	1
RAC1-CDC42/GDP	-0.017	0.12	-9999	-0.39	7	7
NRG2	-0.24	0.29	-9999	-0.58	152	152
mol:GDP	-0.039	0.13	-9999	-0.28	71	71
SOS1	0.015	0.001	-9999	-10000	0	0
MAP2K2	-0.008	0.12	-9999	-0.46	5	5
SRC	0.016	0	-9999	-10000	0	0
mol:cAMP	-0.001	0.002	-9999	-10000	0	0
PTPN11	-0.034	0.13	-9999	-0.43	7	7
MAP2K1	-0.068	0.19	-9999	-0.45	32	32
heart morphogenesis	-0.045	0.13	-9999	-0.46	7	7
RAS family/GDP	-0.021	0.12	-9999	-0.48	5	5
GRB2	0.015	0.001	-9999	-10000	0	0
PRKACA	-0.004	0.007	-9999	-10000	0	0
CHRNE	0.013	0.025	-9999	-0.18	2	2
HSP90AA1	0.016	0	-9999	-10000	0	0
activation of caspase activity	-0.012	0.003	-9999	-10000	0	0
nervous system development	-0.045	0.13	-9999	-0.46	7	7
CDC42	0.016	0	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	0.022	0.02	-9999	-0.36	1	1
CRKL	-0.01	0.1	-9999	-0.36	3	3
mol:PIP3	-0.021	0.006	-9999	-10000	0	0
AKT1	0.002	0.005	-9999	-10000	0	0
PTK2B	0.014	0.031	-9999	-0.58	1	1
RAPGEF1	-0.001	0.099	-9999	-0.37	2	2
RANBP10	0.016	0	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
HGF/MET/SHIP2	-0.058	0.16	-9999	-0.34	86	86
MAP3K5	0.005	0.1	-9999	-0.36	4	4
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.042	0.14	-9999	-0.3	78	78
AP1	-0.11	0.2	-9999	-0.4	111	111
mol:SU11274	0	0	-9999	-10000	0	0
SHC1	0.014	0.028	-9999	-0.51	1	1
apoptosis	-0.22	0.36	-9999	-0.75	111	111
STAT3 (dimer)	-0.015	0.12	-9999	-0.49	1	1
GAB1/CRKL/SHP2/PI3K	-0.036	0.068	-9999	-0.34	2	2
INPP5D	0.004	0.082	-9999	-0.58	7	7
CBL/CRK	0.001	0.096	-9999	-0.33	1	1
PTPN11	0.016	0	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
PLCG1	0.016	0	-9999	-10000	0	0
PTEN	0.016	0	-9999	-10000	0	0
ELK1	-0.003	0.014	-9999	-0.2	1	1
mol:SU5416	0	0	-9999	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.032	0.06	-9999	-0.39	1	1
PAK1	0.009	0.017	-9999	-0.29	1	1
HGF/MET/RANBP10	-0.058	0.16	-9999	-0.34	86	86
HRAS	-0.029	0.14	-9999	-0.38	1	1
DOCK1	-0.002	0.099	-9999	-0.37	2	2
GAB1	-0.018	0.1	-9999	-0.21	78	78
CRK	-0.008	0.1	-9999	-0.32	2	2
mol:PHA665752	0	0	-9999	-10000	0	0
mol:GDP	-0.1	0.19	-9999	-0.47	78	78
JUN	-0.006	0.11	-9999	-0.58	13	13
EntrezGene:200958	0	0	-9999	-10000	0	0
HGF/MET	-0.033	0.093	-9999	-0.2	78	78
PIK3R1	0.016	0	-9999	-10000	0	0
cell morphogenesis	0.012	0.12	-9999	-0.42	2	2
GRB2/SHC	-0.011	0.085	-9999	-0.42	1	1
FOS	-0.17	0.27	-9999	-0.58	110	110
GLMN	0	0	-9999	-10000	0	0
cell motility	-0.003	0.014	-9999	-0.2	1	1
HGF/MET/MUC20	-0.068	0.16	-9999	-0.35	86	86
cell migration	-0.012	0.083	-9999	-0.41	1	1
GRB2	0.016	0	-9999	-10000	0	0
CBL	0.016	0	-9999	-10000	0	0
MET/RANBP10	0.022	0.02	-9999	-0.36	1	1
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.023	0.12	-9999	-0.24	78	78
MET/MUC20	0.011	0.02	-9999	-0.37	1	1
RAP1B	0.008	0.094	-9999	-0.34	2	2
RAP1A	0.008	0.094	-9999	-0.34	2	2
HGF/MET/RANBP9	-0.058	0.16	-9999	-0.34	86	86
RAF1	-0.02	0.13	-9999	-0.35	1	1
STAT3	-0.015	0.12	-9999	-0.5	1	1
cell proliferation	-0.024	0.16	-9999	-0.32	78	78
RPS6KB1	-0.003	0.035	-9999	-10000	0	0
MAPK3	-0.009	0.012	-9999	-10000	0	0
MAPK1	-0.009	0.012	-9999	-10000	0	0
RANBP9	0.016	0	-9999	-10000	0	0
MAPK8	0.023	0.096	-9999	-0.36	5	5
SRC	-0.012	0.11	-9999	-0.47	1	1
PI3K	-0.011	0.084	-9999	-0.42	1	1
MET/Glomulin	0.014	0.018	-9999	-0.32	1	1
SOS1	0.016	0	-9999	-10000	0	0
MAP2K1	-0.01	0.12	-9999	-10000	0	0
MET	0.014	0.028	-9999	-0.51	1	1
MAP4K1	-0.004	0.11	-9999	-0.36	5	5
PTK2	0.016	0	-9999	-10000	0	0
MAP2K2	-0.01	0.12	-9999	-10000	0	0
BAD	0.01	0.005	-9999	-10000	0	0
MAP2K4	0.014	0.095	-9999	-0.33	4	4
SHP2/GRB2/SOS1/GAB1	-0.037	0.068	-9999	-0.3	1	1
INPPL1	0.016	0	-9999	-10000	0	0
PXN	0.016	0	-9999	-10000	0	0
SH3KBP1	0.016	0	-9999	-10000	0	0
HGS	-0.021	0.087	-9999	-0.44	1	1
PLCgamma1/PKC	0.012	0	-9999	-10000	0	0
HGF	-0.12	0.25	-9999	-0.57	85	85
RASA1	0.016	0	-9999	-10000	0	0
NCK1	0.016	0	-9999	-10000	0	0
PTPRJ	0.014	0.031	-9999	-0.58	1	1
NCK/PLCgamma1	-0.014	0.094	-9999	-0.43	1	1
PDPK1	-0.008	0.005	-9999	-10000	0	0
HGF/MET/SHIP	-0.065	0.17	-9999	-0.35	89	89

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.009	0.04	-9999	-0.37	4	4
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	0.003	0.08	-9999	-0.41	13	13
STXBP1	-0.008	0.12	-9999	-0.58	14	14
ACh/CHRNA1	-0.048	0.13	-9999	-0.33	59	59
RAB3GAP2/RIMS1/UNC13B	0.014	0.069	-9999	-0.34	13	13
mol:Ca2+	0	0	-9999	-10000	0	0
UniProt:P30996	0	0	-9999	-10000	0	0
UniProt:Q60393	0	0	-9999	-10000	0	0
CST086	0	0	-9999	-10000	0	0
RIMS1	-0.012	0.11	-9999	-0.57	13	13
mol:ACh	-0.002	0.039	-9999	-0.12	29	29
RAB3GAP2	0.016	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.032	0.085	-9999	-0.38	11	11
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.048	0.13	-9999	-0.33	59	59
UNC13B	0.016	0	-9999	-10000	0	0
CHRNA1	-0.072	0.19	-9999	-0.51	59	59
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.031	0.13	-9999	-0.39	38	38
SNAP25	-0.02	0.086	-9999	-0.26	37	37
VAMP2	0.008	0	-9999	-10000	0	0
SYT1	-0.046	0.18	-9999	-0.56	38	38
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	0.003	0.08	-9999	-0.34	18	18
STX1A/SNAP25 fragment 1/VAMP2	-0.032	0.085	-9999	-0.38	11	11

×

Caspase cascade in apoptosis

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
TOP1	-0.007	0.13	-10000	0	-0.36	32	32
ACTA1	-0.028	0.17	-10000	0	-0.47	34	34
NUMA1	-0.007	0.13	-10000	0	-0.36	32	32
SPTAN1	-0.023	0.16	-10000	0	-0.47	32	32
LIMK1	-0.023	0.16	-10000	0	-0.47	32	32
BIRC3	-0.024	0.15	-10000	0	-0.57	24	24
BIRC2	0.013	0.039	-10000	0	-0.51	2	2
BAX	0.016	0	-10000	0	-10000	0	0
CASP10	-0.039	0.18	-10000	0	-0.41	59	59
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.012	0.042	-10000	0	-0.54	2	2
PTK2	-0.007	0.13	-10000	0	-0.36	32	32
DIABLO	0.016	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.022	0.16	-10000	0	-0.46	32	32
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.016	0	-10000	0	-10000	0	0
GSN	-0.028	0.17	-10000	0	-0.47	37	37
MADD	0.016	0	-10000	0	-10000	0	0
TFAP2A	0.018	0.042	-10000	0	-0.48	1	1
BID	-0.009	0.089	-10000	0	-0.24	38	38
MAP3K1	0.001	0.058	-10000	0	-0.22	6	6
TRADD	0.016	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.023	0.001	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.023	0.16	-10000	0	-0.47	32	32
CASP9	0.016	0	-10000	0	-10000	0	0
DNA repair	-0.006	0.054	0.15	6	-0.2	12	18
neuron apoptosis	0.021	0.062	-10000	0	-0.77	2	2
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.013	0.16	-10000	0	-0.45	32	32
APAF1	0.016	0	-10000	0	-10000	0	0
CASP6	0.017	0.078	-10000	0	-0.35	3	3
TRAF2	0.016	0	-10000	0	-10000	0	0
ICAD/CAD	-0.014	0.16	-10000	0	-0.45	32	32
CASP7	0.011	0.081	0.31	21	-10000	0	21
KRT18	0.013	0.043	-10000	0	-0.64	1	1
apoptosis	-0.007	0.15	0.28	1	-0.43	32	33
DFFA	-0.023	0.16	-10000	0	-0.47	32	32
DFFB	-0.023	0.16	-10000	0	-0.47	32	32
PARP1	0.006	0.055	0.2	12	-0.16	6	18
actin filament polymerization	0.015	0.16	0.44	32	-10000	0	32
TNF	-0.009	0.11	-10000	0	-0.51	17	17
CYCS	-0.002	0.068	-10000	0	-0.21	18	18
SATB1	0.014	0.093	-10000	0	-0.35	5	5
SLK	-0.023	0.16	-10000	0	-0.47	32	32
p15 BID/BAX	0	0.08	-10000	0	-0.3	9	9
CASP2	0.041	0.052	-10000	0	-10000	0	0
JNK cascade	-0.001	0.057	0.21	6	-10000	0	6
CASP3	-0.033	0.17	-10000	0	-0.51	32	32
LMNB2	0.039	0.046	-10000	0	-10000	0	0
RIPK1	0.016	0	-10000	0	-10000	0	0
CASP4	0.014	0.028	-10000	0	-0.51	1	1
Mammalian IAPs/DIABLO	0.014	0.095	-10000	0	-0.33	22	22
negative regulation of DNA binding	0.018	0.041	-10000	0	-0.48	1	1
stress fiber formation	-0.022	0.16	-10000	0	-0.46	32	32
GZMB	-0.058	0.2	-10000	0	-0.49	59	59
CASP1	0.011	0.055	-10000	0	-0.33	9	9
LMNB1	0.039	0.046	-10000	0	-10000	0	0
APP	0.021	0.063	-10000	0	-0.78	2	2
TNFRSF1A	0.016	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.013	0	-10000	0	-10000	0	0
VIM	-0.012	0.15	0.23	12	-0.42	32	44
LMNA	0.039	0.046	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.034	0.055	-10000	0	-10000	0	0
LRDD	0.016	0	-10000	0	-10000	0	0
SREBF1	-0.025	0.16	-10000	0	-0.47	32	32
APAF-1/Caspase 9	0.002	0.047	0.3	3	-10000	0	3
nuclear fragmentation during apoptosis	-0.007	0.13	-10000	0	-0.36	32	32
CFL2	-0.016	0.16	-10000	0	-0.45	32	32
GAS2	-0.057	0.19	-10000	0	-0.42	59	59
positive regulation of apoptosis	0.043	0.046	-10000	0	-10000	0	0
PRF1	-0.024	0.14	-10000	0	-0.55	25	25

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.023	0.07	-9999	-0.32	12	12
epithelial cell differentiation	-0.041	0.087	-9999	-0.41	6	6
ITCH	0.017	0.029	-9999	-0.51	1	1
WWP1	0.035	0.029	-9999	-10000	0	0
FYN	0.011	0.054	-9999	-0.58	3	3
EGFR	-0.008	0.11	-9999	-0.54	15	15
PRL	-0.002	0.061	-9999	-0.51	5	5
neuron projection morphogenesis	0.01	0.12	-9999	-0.46	1	1
PTPRZ1	-0.17	0.26	-9999	-0.55	113	113
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.008	0.13	-9999	-0.52	1	1
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.036	0.14	-9999	-0.36	12	12
ADAM17	0.018	0.008	-9999	-10000	0	0
ErbB4/ErbB4	0.034	0.036	-9999	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	0.005	0.056	-9999	-0.33	1	1
NCOR1	0.016	0	-9999	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.029	0.14	-9999	-0.35	14	14
GRIN2B	-0.031	0.14	-9999	-0.49	6	6
ErbB4/ErbB2/betacellulin	-0.004	0.12	-9999	-0.41	4	4
STAT1	0.01	0.055	-9999	-0.51	4	4
HBEGF	-0.004	0.11	-9999	-0.58	12	12
PRLR	-0.045	0.17	-9999	-0.54	39	39
E4ICDs/ETO2	0.023	0.069	-9999	-0.31	12	12
axon guidance	0.033	0.1	-9999	-0.34	1	1
NEDD4	0.018	0.008	-9999	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	-0.034	0.13	-9999	-0.38	44	44
CBFA2T3	-0.004	0.11	-9999	-0.58	12	12
ErbB4/ErbB2/HBEGF	0.024	0.083	-9999	-0.4	3	3
MAPK3	0.001	0.12	-9999	-0.49	1	1
STAT1 (dimer)	0.031	0.043	-9999	-10000	0	0
MAPK1	0.001	0.12	-9999	-0.49	1	1
JAK2	0.014	0.031	-9999	-0.58	1	1
ErbB4/ErbB2/neuregulin 1 beta	-0.035	0.14	-9999	-0.36	15	15
NRG1	-0.07	0.18	-9999	-0.41	80	80
NRG3	-0.007	0.085	-9999	-0.51	10	10
NRG2	-0.24	0.29	-9999	-0.58	152	152
NRG4	-0.038	0.17	-9999	-0.58	32	32
heart development	0.033	0.1	-9999	-0.34	1	1
neural crest cell migration	-0.035	0.14	-9999	-0.36	15	15
ERBB2	0.014	0.073	-9999	-0.36	13	13
WWOX/E4ICDs	0.034	0.035	-9999	-10000	0	0
SHC1	0.014	0.028	-9999	-0.51	1	1
ErbB4/EGFR/neuregulin 4	-0.001	0.12	-9999	-0.47	6	6
apoptosis	0.017	0.043	-9999	-10000	0	0
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.12	0.18	-9999	-0.32	152	152
ErbB4/ErbB2/epiregulin	-0.047	0.14	-9999	-0.39	12	12
ErbB4/ErbB4/betacellulin/betacellulin	-0.007	0.12	-9999	-0.32	40	40
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.036	0.093	-9999	-0.46	3	3
MDM2	0.028	0.064	-9999	-0.33	2	2
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.057	0.12	-9999	-0.33	12	12
STAT5A	0.038	0.1	-9999	-0.4	1	1
ErbB4/EGFR/neuregulin 1 beta	-0.038	0.15	-9999	-0.38	16	16
DLG4	0.014	0.031	-9999	-0.58	1	1
GRB2/SHC	0.022	0.02	-9999	-0.36	1	1
E4ICDs/TAB2/NCoR1	-0.004	0.017	-9999	-10000	0	0
STAT5A (dimer)	-0.042	0.093	-9999	-0.44	6	6
MAP3K7IP2	0	0	-9999	-10000	0	0
STAT5B (dimer)	0.037	0.095	-9999	-10000	0	0
LRIG1	-0.034	0.16	-9999	-0.58	30	30
EREG	-0.13	0.25	-9999	-0.54	95	95
BTC	-0.051	0.19	-9999	-0.58	40	40
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.031	0.11	-9999	-0.34	1	1
ERBB4	0.034	0.036	-9999	-10000	0	0
STAT5B	0.016	0	-9999	-10000	0	0
YAP1	-0.001	0.012	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0.005	0.12	-9999	-0.48	7	7
glial cell differentiation	0.004	0.017	-9999	-10000	0	0
WWOX	0.014	0.031	-9999	-0.58	1	1
cell proliferation	-0.053	0.17	-9999	-0.47	20	20

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.017	0.25	-10000	0	-0.85	11	11
PCK1	-0.025	0.18	-10000	0	-0.69	9	9
HNF4A	-0.049	0.3	-10000	0	-0.98	16	16
KCNJ11	-0.041	0.32	-10000	0	-0.93	25	25
AKT1	0.016	0.11	-10000	0	-0.38	5	5
response to starvation	-0.004	0.02	-10000	0	-10000	0	0
DLK1	-0.055	0.33	-10000	0	-0.95	29	29
NKX2-1	0.095	0.23	0.66	11	-0.5	1	12
ACADM	-0.021	0.26	-10000	0	-0.83	15	15
TAT	-0.026	0.19	-10000	0	-0.7	12	12
CEBPB	0.012	0.034	-10000	0	-0.59	1	1
CEBPA	0	0.085	-10000	0	-0.52	9	9
TTR	-0.095	0.23	-10000	0	-0.67	22	22
PKLR	-0.041	0.27	-10000	0	-0.82	18	18
APOA1	-0.03	0.3	-10000	0	-0.99	13	13
CPT1C	-0.023	0.26	-10000	0	-0.8	15	15
ALAS1	0.031	0.14	-10000	0	-10000	0	0
TFRC	-0.01	0.19	-10000	0	-0.59	9	9
FOXF1	-0.19	0.28	-10000	0	-0.57	129	129
NF1	0.024	0	-10000	0	-10000	0	0
HNF1A (dimer)	-0.02	0.072	-10000	0	-0.54	4	4
CPT1A	-0.019	0.25	-10000	0	-0.89	11	11
HMGCS1	-0.017	0.25	-10000	0	-0.79	14	14
NR3C1	0.001	0.098	-10000	0	-0.57	9	9
CPT1B	-0.019	0.25	-10000	0	-0.82	13	13
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	-0.013	0.042	-10000	0	-10000	0	0
GCK	-0.067	0.34	-10000	0	-0.94	33	33
CREB1	0.014	0.022	-10000	0	-10000	0	0
IGFBP1	-0.01	0.17	-10000	0	-0.59	11	11
PDX1	-0.074	0.21	-10000	0	-0.67	7	7
UCP2	-0.019	0.25	-10000	0	-0.78	15	15
ALDOB	-0.028	0.29	-10000	0	-0.86	18	18
AFP	-0.072	0.15	-10000	0	-0.46	21	21
BDH1	-0.018	0.25	-10000	0	-0.81	13	13
HADH	-0.008	0.26	-10000	0	-0.86	11	11
F2	-0.029	0.29	-10000	0	-0.98	13	13
HNF1A	-0.02	0.072	-10000	0	-0.54	4	4
G6PC	-0.03	0.13	-10000	0	-0.57	3	3
SLC2A2	-0.018	0.19	-10000	0	-0.66	10	10
INS	-0.006	0.029	-10000	0	-10000	0	0
FOXA1	-0.061	0.2	-10000	0	-0.58	41	41
FOXA3	-0.098	0.22	-10000	0	-0.51	69	69
FOXA2	-0.016	0.3	-10000	0	-0.83	19	19
ABCC8	-0.015	0.26	-10000	0	-0.88	11	11
ALB	-0.088	0.16	-10000	0	-0.46	25	25

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.026	0.002	-9999	-10000	0	0
SMARCC1	0.012	0.014	-9999	-10000	0	0
REL	0.01	0.058	-9999	-0.53	4	4
HDAC7	-0.015	0.14	-9999	-0.37	3	3
JUN	-0.007	0.11	-9999	-0.58	13	13
EP300	0.015	0.001	-9999	-10000	0	0
KAT2B	0.015	0.001	-9999	-10000	0	0
KAT5	0.016	0.001	-9999	-10000	0	0
MAPK14	0.016	0.052	-9999	-0.4	5	5
FOXO1	0.015	0.001	-9999	-10000	0	0
T-DHT/AR	-0.022	0.14	-9999	-0.36	23	23
MAP2K6	0.005	0.068	-9999	-0.56	5	5
BRM/BAF57	0.021	0.008	-9999	-10000	0	0
MAP2K4	0.013	0.007	-9999	-10000	0	0
SMARCA2	0.015	0.004	-9999	-10000	0	0
PDE9A	-0.16	0.4	-9999	-1.2	43	43
NCOA2	-0.023	0.14	-9999	-0.58	23	23
CEBPA	0.002	0.083	-9999	-0.51	9	9
EHMT2	0.014	0.004	-9999	-10000	0	0
cell proliferation	-0.002	0.15	-9999	-0.49	7	7
NR0B1	-0.039	0.14	-9999	-0.51	31	31
EGR1	-0.13	0.25	-9999	-0.58	87	87
RXRs/9cRA	-0.068	0.15	-9999	-0.32	95	95
AR/RACK1/Src	-0.016	0.089	-9999	-0.38	5	5
AR/GR	-0.074	0.15	-9999	-0.32	62	62
GNB2L1	0.015	0.001	-9999	-10000	0	0
PKN1	0.014	0.031	-9999	-0.58	1	1
RCHY1	0.016	0	-9999	-10000	0	0
epidermal growth factor receptor activity	-0.001	0.002	-9999	-10000	0	0
MAPK8	0.018	0.043	-9999	-0.42	3	3
T-DHT/AR/TIF2/CARM1	-0.021	0.12	-9999	-0.43	12	12
SRC	0.027	0.056	-9999	-0.31	1	1
NR3C1	0.001	0.093	-9999	-0.58	9	9
KLK3	-0.12	0.27	-9999	-1	23	23
APPBP2	0.013	0.008	-9999	-10000	0	0
TRIM24	0.011	0.04	-9999	-0.51	2	2
T-DHT/AR/TIP60	-0.01	0.092	-9999	-0.4	5	5
TMPRSS2	-0.22	0.46	-9999	-1.2	64	64
RXRG	-0.15	0.26	-9999	-0.58	95	95
mol:9cRA	0	0.001	-9999	-10000	0	0
RXRA	0.014	0.031	-9999	-0.58	1	1
RXRB	0.015	0.001	-9999	-10000	0	0
CARM1	0.015	0.002	-9999	-10000	0	0
NR2C2	0.012	0.042	-9999	-0.54	2	2
KLK2	-0.029	0.15	-9999	-0.49	11	11
AR	-0.08	0.16	-9999	-0.29	128	128
SENP1	0.015	0.001	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
MDM2	0	0.094	-9999	-0.5	12	12
SRY	-0.001	0.067	-9999	-0.51	6	6
GATA2	-0.007	0.11	-9999	-0.53	15	15
MYST2	0.016	0.001	-9999	-10000	0	0
HOXB13	-0.081	0.22	-9999	-0.57	58	58
T-DHT/AR/RACK1/Src	-0.003	0.092	-9999	-0.39	5	5
positive regulation of transcription	-0.007	0.11	-9999	-0.53	15	15
DNAJA1	0.013	0.008	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.03	0.024	-9999	-10000	0	0
NCOA1	0.02	0.006	-9999	-10000	0	0
SPDEF	-0.1	0.23	-9999	-0.55	73	73
T-DHT/AR/TIF2	0.002	0.094	-9999	-0.36	8	8
T-DHT/AR/Hsp90	-0.01	0.092	-9999	-0.4	5	5
GSK3B	0.014	0.005	-9999	-10000	0	0
NR2C1	0.016	0.002	-9999	-10000	0	0
mol:T-DHT	0.02	0.06	-9999	-0.3	7	7
SIRT1	0.015	0.001	-9999	-10000	0	0
ZMIZ2	0.017	0.007	-9999	-10000	0	0
POU2F1	0.017	0.042	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.052	0.11	-9999	-0.4	12	12
CREBBP	0.015	0.001	-9999	-10000	0	0
SMARCE1	0.015	0.004	-9999	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.016	0.001	-9999	-10000	0	0
HDAC2	0.016	0.001	-9999	-10000	0	0
GNB1/GNG2	0.004	0.095	-9999	-0.36	22	22
forebrain development	-0.084	0.24	-9999	-0.57	54	54
GNAO1	-0.17	0.27	-9999	-0.58	110	110
SMO/beta Arrestin2	0.002	0.093	-9999	-0.41	17	17
SMO	-0.013	0.13	-9999	-0.58	17	17
ARRB2	0.015	0.005	-9999	-10000	0	0
GLI3/SPOP	0.054	0.056	-9999	-10000	0	0
mol:GTP	0	0.002	-9999	-10000	0	0
GSK3B	0.016	0	-9999	-10000	0	0
GNAI2	0.016	0.002	-9999	-10000	0	0
SIN3/HDAC complex	0.04	0.002	-9999	-10000	0	0
GNAI1	0.011	0.054	-9999	-0.58	3	3
XPO1	0.016	0.007	-9999	-10000	0	0
GLI1/Su(fu)	-0.089	0.19	-9999	-0.61	29	29
SAP30	0.016	0.001	-9999	-10000	0	0
mol:GDP	-0.013	0.13	-9999	-0.57	17	17
MIM/GLI2A	0.017	0.008	-9999	-10000	0	0
IFT88	0.016	0	-9999	-10000	0	0
GNAI3	0.016	0.001	-9999	-10000	0	0
GLI2	0.021	0.076	-9999	-10000	0	0
GLI3	0.048	0.059	-9999	-10000	0	0
CSNK1D	0.016	0	-9999	-10000	0	0
CSNK1E	0.016	0	-9999	-10000	0	0
SAP18	0.016	0.001	-9999	-10000	0	0
embryonic digit morphogenesis	0.016	0	-9999	-10000	0	0
GNG2	0.006	0.076	-9999	-0.58	6	6
Gi family/GTP	-0.12	0.22	-9999	-0.4	106	106
SIN3B	0.016	0.001	-9999	-10000	0	0
SIN3A	0.016	0.001	-9999	-10000	0	0
GLI3/Su(fu)	0.067	0.041	-9999	-10000	0	0
GLI2/Su(fu)	0.028	0.087	-9999	-0.29	12	12
FOXA2	-0.053	0.11	-9999	-10000	0	0
neural tube patterning	-0.084	0.24	-9999	-0.57	54	54
SPOP	0.016	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.029	0.045	-9999	-10000	0	0
GNB1	0.016	0	-9999	-10000	0	0
CSNK1G2	0.016	0	-9999	-10000	0	0
CSNK1G3	0.016	0	-9999	-10000	0	0
MTSS1	0.017	0.008	-9999	-10000	0	0
embryonic limb morphogenesis	-0.084	0.24	-9999	-0.57	54	54
SUFU	0.02	0.051	-9999	-10000	0	0
LGALS3	0.014	0.031	-9999	-0.58	1	1
catabolic process	0.059	0.076	-9999	-0.31	5	5
GLI3A/CBP	-0.028	0.13	-9999	-0.34	52	52
KIF3A	0.016	0	-9999	-10000	0	0
GLI1	-0.086	0.25	-9999	-0.59	54	54
RAB23	0.014	0.031	-9999	-0.58	1	1
CSNK1A1	0.016	0	-9999	-10000	0	0
IFT172	0.016	0	-9999	-10000	0	0
RBBP7	0.016	0.001	-9999	-10000	0	0
Su(fu)/Galectin3	0.028	0.048	-9999	-0.3	1	1
GNAZ	-0.11	0.24	-9999	-0.58	76	76
RBBP4	0.016	0.001	-9999	-10000	0	0
CSNK1G1	0.016	0	-9999	-10000	0	0
PIAS1	0.016	0	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
GLI2/SPOP	0.027	0.071	-9999	-10000	0	0
STK36	0.016	0.006	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.094	0.21	-9999	-0.49	57	57
PTCH1	-0.065	0.21	-9999	-0.72	19	19
MIM/GLI1	-0.087	0.25	-9999	-0.62	44	44
CREBBP	-0.028	0.13	-9999	-0.34	52	52
Su(fu)/SIN3/HDAC complex	0.055	0.015	-9999	-10000	0	0

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.001	0.093	-9999	-0.58	9	9
alphaV beta3 Integrin	-0.029	0.14	-9999	-0.42	42	42
PTK2	-0.049	0.13	-9999	-0.45	27	27
positive regulation of JNK cascade	-0.025	0.081	-9999	-0.31	27	27
CDC42/GDP	0.025	0.13	-9999	-0.41	27	27
Rac1/GDP	0.027	0.13	-9999	-0.4	27	27
RAP1B	0.016	0	-9999	-10000	0	0
RAP1A	0.016	0	-9999	-10000	0	0
CTNNB1	0.016	0	-9999	-10000	0	0
CDC42/GTP	-0.03	0.1	-9999	-0.38	27	27
nectin-3/I-afadin	-0.012	0.12	-9999	-0.41	29	29
RAPGEF1	0.017	0.14	-9999	-0.46	27	27
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.006	0.16	-9999	-0.53	27	27
PDGFB-D/PDGFRB	0.001	0.093	-9999	-0.57	9	9
TLN1	0.016	0.07	-9999	-0.32	6	6
Rap1/GTP	-0.025	0.085	-9999	-0.32	27	27
IQGAP1	0.016	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.03	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.012	0.12	-9999	-0.41	29	29
PVR	0.016	0	-9999	-10000	0	0
Necl-5(dimer)	0.016	0	-9999	-10000	0	0
mol:GDP	0.017	0.16	-9999	-0.51	27	27
MLLT4	0.016	0	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
PI3K	0.012	0.099	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.022	0.023	-9999	-0.41	1	1
positive regulation of lamellipodium assembly	-0.027	0.087	-9999	-0.32	28	28
PVRL1	0.014	0.031	-9999	-0.58	1	1
PVRL3	-0.032	0.16	-9999	-0.57	29	29
PVRL2	0.016	0	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
CDH1	-0.006	0.11	-9999	-0.58	13	13
CLDN1	-0.016	0.13	-9999	-0.55	20	20
JAM-A/CLDN1	-0.006	0.12	-9999	-0.32	39	39
SRC	-0.05	0.16	-9999	-0.6	27	27
ITGB3	-0.054	0.19	-9999	-0.58	42	42
nectin-1(dimer)/I-afadin/I-afadin	0.022	0.023	-9999	-0.41	1	1
FARP2	0.012	0.15	-9999	-0.5	27	27
RAC1	0.016	0	-9999	-10000	0	0
CTNNA1	0.016	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.002	0.1	-9999	-0.34	29	29
nectin-1/I-afadin	0.022	0.023	-9999	-0.41	1	1
nectin-2/I-afadin	0.023	0	-9999	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0.021	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.001	0.1	-9999	-0.34	30	30
CDC42/GTP/IQGAP1/filamentous actin	0.021	0	-9999	-10000	0	0
F11R	0.014	0.031	-9999	-0.58	1	1
positive regulation of filopodium formation	-0.025	0.081	-9999	-0.31	27	27
alphaV/beta3 Integrin/Talin	-0.003	0.13	-9999	-0.43	15	15
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.023	0	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.023	0	-9999	-10000	0	0
PIP5K1C	0.008	0.074	-9999	-0.36	6	6
VAV2	0.008	0.16	-9999	-0.51	29	29
RAP1/GDP	-0.029	0.1	-9999	-0.38	27	27
ITGAV	0.014	0.031	-9999	-0.58	1	1
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.002	0.1	-9999	-0.34	29	29
nectin-3(dimer)/I-afadin/I-afadin	-0.012	0.12	-9999	-0.41	29	29
Rac1/GTP	-0.033	0.11	-9999	-0.39	28	28
PTPRM	-0.003	0.082	-9999	-0.25	33	33
E-cadherin/beta catenin/alpha catenin	-0.01	0.055	-9999	-0.55	1	1
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0

×

IL27-mediated signaling events

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
TGFB1	0.019	0.005	-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	0.029	0.13	0.47	8	-10000	0	8
IL27/IL27R/JAK1	-0.058	0.16	-10000	0	-0.7	5	5
TBX21	-0.045	0.2	-10000	0	-0.51	32	32
IL12B	-0.008	0.091	-10000	0	-0.51	11	11
IL12A	0.006	0.049	-10000	0	-0.37	6	6
IL6ST	-0.08	0.22	-10000	0	-0.58	56	56
IL27RA/JAK1	0.016	0.038	-10000	0	-10000	0	0
IL27	-0.019	0.12	-10000	0	-0.51	20	20
TYK2	0.014	0.007	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.12	0.16	-10000	0	-10000	0	0
T-helper 2 cell differentiation	0.029	0.13	0.47	8	-10000	0	8
T cell proliferation during immune response	0.029	0.13	0.47	8	-10000	0	8
MAPKKK cascade	-0.029	0.13	-10000	0	-0.47	8	8
STAT3	0.016	0	-10000	0	-10000	0	0
STAT2	0.016	0	-10000	0	-10000	0	0
STAT1	0.01	0.055	-10000	0	-0.5	4	4
IL12RB1	-0.022	0.14	-10000	0	-0.54	24	24
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.068	0.22	-10000	0	-0.51	41	41
IL27/IL27R/JAK2/TYK2	-0.029	0.13	-10000	0	-0.48	8	8
positive regulation of T cell mediated cytotoxicity	-0.029	0.13	-10000	0	-0.47	8	8
STAT1 (dimer)	-0.085	0.21	0.48	13	-0.62	20	33
JAK2	0.012	0.032	-10000	0	-0.58	1	1
JAK1	0.015	0.003	-10000	0	-10000	0	0
STAT2 (dimer)	-0.021	0.12	-10000	0	-0.47	7	7
T cell proliferation	-0.16	0.19	-10000	0	-0.48	45	45
IL12/IL12R/TYK2/JAK2	0.001	0.082	-10000	0	-10000	0	0
IL17A	-0.12	0.15	-10000	0	-10000	0	0
mast cell activation	0.029	0.13	0.47	8	-10000	0	8
IFNG	-0.008	0.034	-10000	0	-0.09	9	9
T cell differentiation	-0.005	0.006	-10000	0	-0.019	33	33
STAT3 (dimer)	-0.021	0.12	-10000	0	-0.49	6	6
STAT5A (dimer)	-0.022	0.12	-10000	0	-0.47	7	7
STAT4 (dimer)	-0.037	0.14	-10000	0	-0.5	10	10
STAT4	-0.016	0.13	-10000	0	-0.58	19	19
T cell activation	-0.01	0.008	0.051	4	-10000	0	4
IL27R/JAK2/TYK2	-0.029	0.13	-10000	0	-0.61	2	2
GATA3	-0.069	0.35	-10000	0	-1.4	23	23
IL18	0.007	0.051	-10000	0	-0.42	5	5
positive regulation of mast cell cytokine production	-0.02	0.12	-10000	0	-0.48	6	6
IL27/EBI3	-0.015	0.11	-10000	0	-0.39	28	28
IL27RA	0.006	0.039	-10000	0	-10000	0	0
IL6	-0.25	0.29	-10000	0	-0.57	162	162
STAT5A	0.014	0.031	-10000	0	-0.58	1	1
monocyte differentiation	-0.001	0.002	-10000	0	-10000	0	0
IL2	0.004	0.023	-10000	0	-10000	0	0
IL1B	-0.022	0.11	-10000	0	-0.4	30	30
EBI3	-0.002	0.09	-10000	0	-0.53	10	10
TNF	-0.005	0.081	-10000	0	-0.37	17	17

×

EGFR-dependent Endothelin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.016	0	-9999	-10000	0	0
EGFR	-0.008	0.11	-9999	-0.54	15	15
EGF/EGFR	-0.07	0.12	-9999	-0.3	59	59
EGF/EGFR dimer/SHC/GRB2/SOS1	0.015	0.09	-9999	-0.49	1	1
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.071	0.21	-9999	-0.58	52	52
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.018	0.12	-9999	-0.51	22	22
EGF/EGFR dimer/SHC	-0.005	0.1	-9999	-0.31	37	37
mol:GDP	-0.025	0.076	-9999	-0.48	1	1
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.005	0.075	-9999	-0.53	7	7
GRB2/SOS1	0.023	0	-9999	-10000	0	0
HRAS/GTP	-0.023	0.068	-9999	-0.45	1	1
SHC1	0.014	0.028	-9999	-0.51	1	1
HRAS/GDP	-0.023	0.07	-9999	-0.45	1	1
FRAP1	0.012	0.085	-9999	-0.47	1	1
EGF/EGFR dimer	-0.018	0.12	-9999	-0.37	37	37
SOS1	0.016	0	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.048	0.16	-9999	-0.42	58	58

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.017	0	-9999	-10000	0	0
ELF1	-0.002	0.09	-9999	-0.34	18	18
CCNA2	-0.12	0.23	-9999	-0.51	94	94
PIK3CA	0.017	0	-9999	-10000	0	0
JAK3	0.014	0.039	-9999	-0.51	2	2
PIK3R1	0.016	0	-9999	-10000	0	0
JAK1	0.017	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.061	0.1	-9999	-0.62	4	4
SHC1	0.015	0.028	-9999	-0.51	1	1
SP1	-0.004	0.098	-9999	-0.34	28	28
IL2RA	-0.023	0.2	-9999	-0.61	33	33
IL2RB	0.007	0.075	-9999	-0.56	6	6
SOS1	0.016	0	-9999	-10000	0	0
IL2RG	-0.01	0.12	-9999	-0.54	17	17
G1/S transition of mitotic cell cycle	-0.062	0.25	-9999	-0.76	33	33
PTPN11	0.017	0	-9999	-10000	0	0
CCND2	-0.03	0.23	-9999	-0.81	28	28
LCK	0.007	0.073	-9999	-0.55	6	6
GRB2	0.016	0	-9999	-10000	0	0
IL2	0.005	0.007	-9999	-10000	0	0
CDK6	-0.003	0.1	-9999	-0.58	11	11
CCND3	0.068	0.09	-9999	-0.56	3	3

×

Regulation of nuclear SMAD2/3 signaling

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
EP300	0.016	0.007	-10000	0	-10000	0	0
HSPA8	0.015	0.002	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.064	0.15	0.22	3	-0.38	58	61
AKT1	0.015	0.015	-10000	0	-10000	0	0
GSC	-0.007	0.087	-10000	0	-10000	0	0
NKX2-5	-0.078	0.19	-10000	0	-0.5	59	59
muscle cell differentiation	0.052	0.087	0.4	10	-10000	0	10
SMAD2-3/SMAD4/SP1	0.048	0.097	-10000	0	-0.38	5	5
SMAD4	0.01	0.051	-10000	0	-10000	0	0
CBFB	0.016	0	-10000	0	-10000	0	0
SAP18	0.015	0.001	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.028	0.04	-10000	0	-10000	0	0
SMAD3/SMAD4/VDR	-0.001	0.039	-10000	0	-0.48	1	1
MYC	-0.013	0.13	-10000	0	-0.58	18	18
CDKN2B	-0.015	0.27	-10000	0	-1.4	11	11
AP1	-0.052	0.21	-10000	0	-0.66	20	20
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.069	0.023	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.026	0.078	-10000	0	-0.32	8	8
SP3	0.019	0	-10000	0	-10000	0	0
CREB1	0.016	0	-10000	0	-10000	0	0
FOXH1	-0.1	0.22	-10000	0	-0.5	83	83
SMAD3/SMAD4/GR	-0.018	0.078	-10000	0	-0.44	9	9
GATA3	-0.028	0.15	-10000	0	-0.57	25	25
SKI/SIN3/HDAC complex/NCoR1	0.054	0.009	-10000	0	-10000	0	0
MEF2C/TIF2	-0.077	0.2	-10000	0	-0.57	32	32
endothelial cell migration	0.007	0.17	1.4	5	-10000	0	5
MAX	0.014	0.007	-10000	0	-10000	0	0
RBBP7	0.015	0.001	-10000	0	-10000	0	0
RBBP4	0.015	0.001	-10000	0	-10000	0	0
RUNX2	0.007	0.069	-10000	0	-0.52	6	6
RUNX3	-0.008	0.12	-10000	0	-0.58	14	14
RUNX1	0.016	0	-10000	0	-10000	0	0
CTBP1	0.014	0.028	-10000	0	-0.51	1	1
NR3C1	-0.001	0.093	-10000	0	-0.58	9	9
VDR	0.012	0.042	-10000	0	-0.54	2	2
CDKN1A	0.056	0.11	-10000	0	-1.4	1	1
KAT2B	0.016	0.002	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	-0.042	0.15	-10000	0	-0.35	37	37
DCP1A	0.016	0	-10000	0	-10000	0	0
SKI	0.015	0.001	-10000	0	-10000	0	0
SERPINE1	-0.008	0.18	-10000	0	-1.4	5	5
SMAD3/SMAD4/ATF2	-0.006	0.044	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	-0.073	0.16	-10000	0	-0.4	64	64
SAP30	0.015	0.001	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.014	0.026	-10000	0	-10000	0	0
JUN	-0.052	0.21	-10000	0	-0.66	20	20
SMAD3/SMAD4/IRF7	-0.021	0.08	-10000	0	-0.4	6	6
TFE3	0.022	0.012	-10000	0	-10000	0	0
COL1A2	-0.038	0.26	-10000	0	-0.99	23	23
mesenchymal cell differentiation	0.013	0.058	0.32	6	-10000	0	6
DLX1	-0.04	0.16	-10000	0	-0.51	37	37
TCF3	0.016	0	-10000	0	-10000	0	0
FOS	-0.16	0.28	-10000	0	-0.58	110	110
SMAD3/SMAD4/Max	-0.009	0.042	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.032	0.007	-10000	0	-10000	0	0
ZBTB17	0.017	0.012	-10000	0	-10000	0	0
LAMC1	0.046	0.062	-10000	0	-0.63	1	1
TGIF2/HDAC complex/SMAD3/SMAD4	-0.006	0.044	-10000	0	-10000	0	0
IRF7	-0.004	0.1	-10000	0	-0.52	13	13
ESR1	-0.084	0.22	-10000	0	-0.57	61	61
HNF4A	-0.039	0.15	-10000	0	-0.51	35	35
MEF2C	-0.07	0.19	-10000	0	-0.59	21	21
SMAD2-3/SMAD4	0.01	0.064	-10000	0	-0.32	1	1
Cbp/p300/Src-1	0.033	0.011	-10000	0	-10000	0	0
IGHV3OR16-13	-0.003	0.017	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.016	0	-10000	0	-10000	0	0
CREBBP	0.016	0.005	-10000	0	-10000	0	0
SKIL	0.014	0.028	-10000	0	-0.51	1	1
HDAC1	0.015	0.001	-10000	0	-10000	0	0
HDAC2	0.015	0.001	-10000	0	-10000	0	0
SNIP1	0.015	0.001	-10000	0	-10000	0	0
GCN5L2	0.001	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.036	0.066	-10000	0	-0.33	1	1
MSG1/HSC70	0.015	0.045	-10000	0	-0.36	5	5
SMAD2	0.017	0.02	-10000	0	-10000	0	0
SMAD3	0.01	0.046	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.039	0.045	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.011	0.024	-10000	0	-10000	0	0
NCOR1	0.015	0.001	-10000	0	-10000	0	0
NCOA2	-0.023	0.14	-10000	0	-0.58	23	23
NCOA1	0.016	0	-10000	0	-10000	0	0
MYOD/E2A	0.012	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.062	0.092	-10000	0	-0.38	3	3
IFNB1	0.013	0.1	-10000	0	-0.47	8	8
SMAD3/SMAD4/MEF2C	-0.068	0.19	-10000	0	-0.58	23	23
CITED1	0.008	0.061	-10000	0	-0.51	5	5
SMAD2-3/SMAD4/ARC105	0.035	0.064	-10000	0	-10000	0	0
RBL1	0.013	0.039	-10000	0	-0.51	2	2
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.041	0.11	-10000	0	-0.49	11	11
RUNX1-3/PEBPB2	0.017	0.073	-10000	0	-0.34	14	14
SMAD7	-0.002	0.18	-10000	0	-0.59	10	10
MYC/MIZ-1	-0.01	0.1	-10000	0	-0.42	18	18
SMAD3/SMAD4	0.006	0.069	0.25	1	-0.42	4	5
IL10	-0.008	0.18	-10000	0	-0.62	21	21
PIASy/HDAC complex	0.015	0.006	-10000	0	-10000	0	0
PIAS3	0.016	0.003	-10000	0	-10000	0	0
CDK2	0.016	0.004	-10000	0	-10000	0	0
IL5	-0.002	0.12	-10000	0	-0.5	6	6
CDK4	0.015	0.028	-10000	0	-0.51	1	1
PIAS4	0.015	0.006	-10000	0	-10000	0	0
ATF3	-0.09	0.23	-10000	0	-0.58	64	64
SMAD3/SMAD4/SP1	0.03	0.093	-10000	0	-0.36	7	7
FOXG1	-0.069	0.18	-10000	0	-0.51	50	50
FOXO3	0.026	0.02	-10000	0	-10000	0	0
FOXO1	0.026	0.02	-10000	0	-10000	0	0
FOXO4	0.025	0.028	-10000	0	-0.35	1	1
heart looping	-0.069	0.19	-10000	0	-0.59	21	21
CEBPB	0.014	0.032	-10000	0	-0.57	1	1
SMAD3/SMAD4/DLX1	-0.038	0.1	-10000	0	-0.34	19	19
MYOD1	0	0	-10000	0	-10000	0	0
SMAD3/SMAD4/HNF4	-0.036	0.1	-10000	0	-0.34	19	19
SMAD3/SMAD4/GATA3	-0.041	0.12	-10000	0	-0.4	21	21
SnoN/SIN3/HDAC complex/NCoR1	0.014	0.028	-10000	0	-0.51	1	1
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.025	0.09	-10000	0	-0.39	8	8
SMAD3/SMAD4/SP1-3	0.042	0.085	-10000	0	-0.37	1	1
MED15	0.016	0	-10000	0	-10000	0	0
SP1	0.018	0.036	-10000	0	-10000	0	0
SIN3B	0.015	0.001	-10000	0	-10000	0	0
SIN3A	0.015	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.077	0.18	-10000	0	-0.45	28	28
ITGB5	0.055	0.072	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.055	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.14	0.18	-10000	0	-0.37	128	128
AR	-0.2	0.28	-10000	0	-0.58	128	128
negative regulation of cell growth	0.009	0.1	-10000	0	-0.4	5	5
SMAD3/SMAD4/MYOD	-0.008	0.047	-10000	0	-10000	0	0
E2F5	0.012	0.042	-10000	0	-0.54	2	2
E2F4	0.016	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.014	0.13	-10000	0	-0.39	9	9
SMAD2-3/SMAD4/FOXO1-3a-4	0.044	0.08	-10000	0	-0.34	11	11
TFDP1	0.016	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	-0.051	0.21	-10000	0	-0.67	20	20
SMAD3/SMAD4/RUNX2	-0.011	0.06	-10000	0	-0.32	6	6
TGIF2	0.016	0	-10000	0	-10000	0	0
TGIF1	0.016	0	-10000	0	-10000	0	0
ATF2	0.016	0	-10000	0	-10000	0	0

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.016	0	-10000	0	-10000	0	0
ANTXR2	-0.018	0.14	-10000	0	-0.58	20	20
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.004	0.017	-10000	0	-0.075	20	20
monocyte activation	-0.006	0.09	-10000	0	-0.41	16	16
MAP2K2	-0.001	0.006	-10000	0	-10000	0	0
MAP2K1	-0.003	0.014	-10000	0	-10000	0	0
MAP2K7	-0.003	0.014	-10000	0	-10000	0	0
MAP2K6	-0.008	0.039	-10000	0	-0.31	5	5
CYAA	-0.001	0.073	-10000	0	-0.3	20	20
MAP2K4	-0.003	0.014	-10000	0	-10000	0	0
IL1B	-0.012	0.089	-10000	0	-0.29	31	31
Channel	0.001	0.079	-10000	0	-0.32	20	20
NLRP1	-0.008	0.038	-10000	0	-0.31	5	5
CALM1	0.016	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.005	0.019	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.004	0.017	0.075	20	-10000	0	20
MAPK3	-0.003	0.014	-10000	0	-10000	0	0
MAPK1	-0.003	0.014	-10000	0	-10000	0	0
PGR	-0.1	0.15	-10000	0	-0.32	115	115
PA/Cellular Receptors	0	0.086	-10000	0	-0.35	20	20
apoptosis	-0.004	0.017	-10000	0	-0.075	20	20
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.002	0.074	-10000	0	-0.3	20	20
macrophage activation	0.018	0.016	-10000	0	-10000	0	0
TNF	-0.009	0.11	-10000	0	-0.51	17	17
VCAM1	-0.006	0.09	-10000	0	-0.41	16	16
platelet activation	-0.005	0.019	-10000	0	-10000	0	0
MAPKKK cascade	-0.013	0.021	0.14	1	-10000	0	1
IL18	0.008	0.052	-10000	0	-0.26	10	10
negative regulation of macrophage activation	-0.004	0.017	-10000	0	-0.075	20	20
LEF	-0.004	0.017	-10000	0	-0.075	20	20
CASP1	-0.008	0.031	-10000	0	-0.17	8	8
mol:cAMP	-0.005	0.019	-10000	0	-10000	0	0
necrosis	-0.004	0.017	-10000	0	-0.075	20	20
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.002	0.074	-10000	0	-0.3	20	20
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.053	0.082	-10000	0	-0.57	2	2
UGCG	-0.018	0.17	-10000	0	-0.66	22	22
AKT1/mTOR/p70S6K/Hsp90/TERT	0.024	0.12	-10000	0	-0.38	19	19
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.015	0.17	-10000	0	-0.65	22	22
mol:DAG	0	0.003	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.038	0.12	-10000	0	-0.4	32	32
FRAP1	0.044	0.17	-10000	0	-0.46	32	32
FOXO3	0.055	0.15	-10000	0	-0.45	21	21
AKT1	0.047	0.16	-10000	0	-0.46	25	25
GAB2	0.015	0.004	-10000	0	-10000	0	0
SMPD1	0.023	0.029	-10000	0	-10000	0	0
SGMS1	0.023	0.029	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
mol:GDP	0.024	0.007	-10000	0	-10000	0	0
CALM1	0.016	0	-10000	0	-10000	0	0
cell proliferation	0.013	0.14	-10000	0	-0.34	31	31
EIF3A	0.016	0	-10000	0	-10000	0	0
PI3K	0.028	0.009	-10000	0	-10000	0	0
RPS6KB1	0.018	0.038	-10000	0	-10000	0	0
mol:sphingomyelin	0	0.003	-10000	0	-10000	0	0
natural killer cell activation	0	0.003	-10000	0	-0.013	15	15
JAK3	0.015	0.039	-10000	0	-0.5	2	2
PIK3R1	0.018	0.005	-10000	0	-10000	0	0
JAK1	0.018	0.004	-10000	0	-10000	0	0
NFKB1	0.016	0	-10000	0	-10000	0	0
MYC	0.025	0.25	-10000	0	-0.94	21	21
MYB	-0.016	0.13	-10000	0	-1.3	1	1
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.05	0.13	-10000	0	-0.61	7	7
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.035	0.035	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.05	0.12	-10000	0	-0.59	7	7
Rac1/GDP	0.031	0.01	-10000	0	-10000	0	0
T cell proliferation	0.055	0.12	-10000	0	-0.58	6	6
SHC1	0.014	0.028	-10000	0	-0.51	1	1
RAC1	0.016	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.002	0.013	-10000	0	-0.031	45	45
PRKCZ	0.055	0.12	-10000	0	-0.61	6	6
NF kappa B1 p50/RelA	-0.028	0.12	-10000	0	-0.45	20	20
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.046	0.087	-10000	0	-0.49	7	7
HSP90AA1	0.016	0	-10000	0	-10000	0	0
RELA	0.016	0	-10000	0	-10000	0	0
IL2RA	-0.036	0.16	-10000	0	-0.54	33	33
IL2RB	0.008	0.075	-10000	0	-0.56	6	6
TERT	-0.21	0.26	-10000	0	-0.51	153	153
E2F1	-0.007	0.084	-10000	0	-0.25	24	24
SOS1	0.016	0.004	-10000	0	-10000	0	0
RPS6	0.016	0	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.006	0.015	45	-10000	0	45
PTPN11	0.016	0.004	-10000	0	-10000	0	0
IL2RG	-0.008	0.12	-10000	0	-0.54	17	17
actin cytoskeleton organization	0.055	0.12	-10000	0	-0.58	6	6
GRB2	0.016	0.004	-10000	0	-10000	0	0
IL2	0.007	0.008	-10000	0	-10000	0	0
PIK3CA	0.018	0.004	-10000	0	-10000	0	0
Rac1/GTP	0.039	0.013	-10000	0	-10000	0	0
LCK	0.009	0.073	-10000	0	-0.55	6	6
BCL2	0.035	0.22	-10000	0	-0.8	19	19

×

Signaling events mediated by PTP1B

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
PDGFRB	0.001	0.093	-10000	0	-0.58	9	9
Jak2/Leptin Receptor	-0.005	0.093	0.2	14	-0.36	8	22
PTP1B/AKT1	0.026	0.048	-10000	0	-0.24	2	2
FYN	0.011	0.054	-10000	0	-0.58	3	3
p210 bcr-abl/PTP1B	0.02	0.053	-10000	0	-0.24	4	4
EGFR	-0.007	0.11	-10000	0	-0.54	15	15
EGF/EGFR	-0.026	0.073	-10000	0	-0.27	17	17
CSF1	-0.006	0.11	-10000	0	-0.58	13	13
AKT1	0.016	0.001	-10000	0	-10000	0	0
INSR	0.016	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.002	0.1	-10000	0	-0.29	22	22
Insulin Receptor/Insulin	-0.004	0.025	-10000	0	-10000	0	0
HCK	-0.012	0.12	-10000	0	-0.56	17	17
CRK	0.016	0	-10000	0	-10000	0	0
TYK2	0.028	0.05	-10000	0	-0.25	2	2
EGF	-0.017	0.12	-10000	0	-0.5	22	22
YES1	0.016	0	-10000	0	-10000	0	0
CAV1	0.023	0.067	-10000	0	-0.26	4	4
TXN	0.013	0.039	-10000	0	-0.51	2	2
PTP1B/IRS1/GRB2	0.03	0.068	-10000	0	-0.38	4	4
cell migration	-0.02	0.053	0.24	4	-10000	0	4
STAT3	0.015	0.001	-10000	0	-10000	0	0
PRLR	-0.044	0.17	-10000	0	-0.53	39	39
ITGA2B	-0.026	0.14	-10000	0	-0.51	28	28
CSF1R	-0.021	0.14	-10000	0	-0.57	22	22
Prolactin Receptor/Prolactin	-0.04	0.13	-10000	0	-0.38	44	44
FGR	0.014	0.031	-10000	0	-0.58	1	1
PTP1B/p130 Cas	0.027	0.049	-10000	0	-0.25	2	2
Crk/p130 Cas	0.036	0.048	-10000	0	-0.24	1	1
DOK1	0.029	0.062	-10000	0	-0.27	5	5
JAK2	0.012	0.072	-10000	0	-0.34	5	5
Jak2/Leptin Receptor/Leptin	-0.073	0.15	-10000	0	-0.43	39	39
PIK3R1	0.016	0	-10000	0	-10000	0	0
PTPN1	0.02	0.053	-10000	0	-0.24	4	4
LYN	0.016	0	-10000	0	-10000	0	0
CDH2	-0.041	0.16	-10000	0	-0.51	38	38
SRC	0.028	0.022	-10000	0	-10000	0	0
ITGB3	-0.054	0.19	-10000	0	-0.58	42	42
CAT1/PTP1B	0	0.11	-10000	0	-0.38	10	10
CAPN1	0.016	0.002	-10000	0	-10000	0	0
CSK	0.016	0	-10000	0	-10000	0	0
PI3K	0	0.021	-10000	0	-10000	0	0
mol:H2O2	0	0.003	-10000	0	-10000	0	0
STAT3 (dimer)	-0.072	0.15	-10000	0	-0.46	39	39
negative regulation of transcription	0.016	0.073	-10000	0	-0.33	5	5
FCGR2A	-0.001	0.091	-10000	0	-0.51	11	11
FER	0.013	0.045	-10000	0	-0.58	2	2
alphaIIb/beta3 Integrin	-0.061	0.17	-10000	0	-0.41	66	66
BLK	-0.054	0.18	-10000	0	-0.56	42	42
Insulin Receptor/Insulin/Shc	0.021	0.017	-10000	0	-0.3	1	1
RHOA	0.016	0.002	-10000	0	-10000	0	0
LEPR	-0.007	0.11	-10000	0	-0.57	14	14
BCAR1	0.016	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.016	0	-10000	0	-10000	0	0
mol:NADPH	0.001	0.002	-10000	0	-10000	0	0
TRPV6	-0.021	0.13	-10000	0	-0.45	13	13
PRL	0	0.061	-10000	0	-0.51	5	5
SOCS3	-0.14	0.43	-10000	0	-1.4	38	38
SPRY2	0.004	0.083	-10000	0	-0.58	7	7
Insulin Receptor/Insulin/IRS1	0.014	0.052	-10000	0	-0.36	7	7
CSF1/CSF1R	0.006	0.12	-10000	0	-0.37	20	20
Ras protein signal transduction	0.011	0.018	-10000	0	-10000	0	0
IRS1	0.004	0.082	-10000	0	-0.58	7	7
INS	0.001	0.001	-10000	0	-10000	0	0
LEP	-0.062	0.19	-10000	0	-0.56	46	46
STAT5B	0.023	0.054	-10000	0	-0.23	4	4
STAT5A	0.023	0.054	-10000	0	-0.23	4	4
GRB2	0.016	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.019	0.072	-10000	0	-0.31	9	9
CSN2	-0.012	0.047	-10000	0	-10000	0	0
PIK3CA	0.016	0	-10000	0	-10000	0	0
LAT	0.024	0.035	-10000	0	-0.39	1	1
YBX1	0.024	0.027	-10000	0	-0.49	1	1
LCK	0.006	0.073	-10000	0	-0.55	6	6
SHC1	0.014	0.028	-10000	0	-0.51	1	1
NOX4	-0.019	0.13	-10000	0	-0.5	24	24

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.014	0.028	-9999	-0.51	1	1
Syndecan-3/Src/Cortactin	-0.064	0.11	-9999	-0.81	1	1
Syndecan-3/Neurocan	-0.009	0.051	-9999	-0.27	12	12
POMC	-0.006	0.11	-9999	-0.54	14	14
EGFR	-0.008	0.11	-9999	-0.54	15	15
Syndecan-3/EGFR	-0.012	0.06	-9999	-0.28	16	16
AGRP	0.005	0.039	-9999	-0.51	2	2
NCSTN	0.016	0	-9999	-10000	0	0
PSENEN	0.016	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.016	0	-9999	-10000	0	0
APH1A	0.016	0	-9999	-10000	0	0
NCAN	-0.007	0.089	-9999	-0.51	11	11
long-term memory	-0.004	0.048	-9999	-0.44	3	3
Syndecan-3/IL8	-0.042	0.11	-9999	-0.29	51	51
PSEN1	0.016	0	-9999	-10000	0	0
Src/Cortactin	0.022	0.02	-9999	-0.36	1	1
FYN	0.011	0.054	-9999	-0.58	3	3
limb bud formation	-0.002	0.033	-9999	-0.62	1	1
MC4R	-0.002	0.061	-9999	-0.51	5	5
SRC	0.016	0	-9999	-10000	0	0
PTN	-0.13	0.25	-9999	-0.56	91	91
FGFR/FGF/Syndecan-3	-0.002	0.033	-9999	-0.63	1	1
neuron projection morphogenesis	-0.046	0.12	-9999	-0.6	2	2
Syndecan-3/AgRP	-0.003	0.036	-9999	-0.36	3	3
Syndecan-3/AgRP/MC4R	0.001	0.047	-9999	-0.58	1	1
Fyn/Cortactin	0.018	0.045	-9999	-0.4	4	4
SDC3	-0.002	0.033	-9999	-0.63	1	1
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.041	0.11	-9999	-0.29	51	51
IL8	-0.069	0.21	-9999	-0.57	51	51
Syndecan-3/Fyn/Cortactin	0.034	0.054	-9999	-0.46	3	3
Syndecan-3/CASK	-0.002	0.032	-9999	-0.6	1	1
alpha-MSH/MC4R	-0.005	0.089	-9999	-0.38	19	19
Gamma Secretase	0.046	0	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.016	0	-10000	0	-10000	0	0
HDAC4	0.016	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.005	0.1	0.36	27	-10000	0	27
CDKN1A	-0.002	0.041	-10000	0	-0.77	1	1
KAT2B	0.016	0	-10000	0	-10000	0	0
BAX	0.016	0	-10000	0	-10000	0	0
FOXO3	0	0	-10000	0	-10000	0	0
FOXO1	0.016	0	-10000	0	-10000	0	0
FOXO4	0.026	0.008	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.016	0	-10000	0	-10000	0	0
TAT	-0.015	0.11	-10000	0	-0.51	17	17
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.013	0	-10000	0	-10000	0	0
PPARGC1A	-0.23	0.29	-10000	0	-0.57	145	145
FHL2	0.014	0.031	-10000	0	-0.58	1	1
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0	0.008	-10000	0	-10000	0	0
HIST2H4A	-0.005	0.1	-10000	0	-0.36	27	27
SIRT1/FOXO3a	0	0.007	-10000	0	-10000	0	0
SIRT1	0.001	0.011	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0	0.008	-10000	0	-10000	0	0
SIRT1/Histone H1b	-0.01	0.033	-10000	0	-10000	0	0
apoptosis	0	0.008	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.14	0.17	-10000	0	-0.35	145	145
p53/SIRT1	0.001	0.021	0.4	1	-10000	0	1
SIRT1/FOXO4	0	0.01	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	0	0.018	-10000	0	-0.31	1	1
HIST1H1E	0.01	0.048	-10000	0	-10000	0	0
SIRT1/p300	0	0.008	-10000	0	-10000	0	0
muscle cell differentiation	0	0.008	-10000	0	-10000	0	0
TP53	0.001	0.011	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0	0.008	-10000	0	-10000	0	0
CREBBP	0.016	0	-10000	0	-10000	0	0
MEF2D	0.016	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.017	0.077	-10000	0	-0.36	17	17
ACSS2	0.022	0.021	-10000	0	-0.36	1	1
SIRT1/PCAF/MYOD	0	0.008	-10000	0	-10000	0	0

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.018	0.006	-10000	0	-10000	0	0
PRKCZ	0.012	0.044	-10000	0	-0.58	2	2
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.016	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.017	0.048	-10000	0	-0.29	2	2
IRAK/TOLLIP	0.034	0.004	-10000	0	-10000	0	0
IKBKB	0.016	0	-10000	0	-10000	0	0
IKBKG	0.016	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.094	0.19	-10000	0	-0.39	101	101
IL1A	-0.092	0.22	-10000	0	-0.54	69	69
IL1B	-0.018	0.13	-10000	0	-0.4	37	37
IRAK/TRAF6/p62/Atypical PKCs	-0.001	0.018	-10000	0	-10000	0	0
IL1R2	-0.04	0.16	-10000	0	-0.52	37	37
IL1R1	0.014	0.031	-10000	0	-0.58	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.031	0.062	0.22	7	-0.33	2	9
TOLLIP	0.016	0	-10000	0	-10000	0	0
TICAM2	0.014	0.031	-10000	0	-0.58	1	1
MAP3K3	0.016	0	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.011	0	-10000	0	-10000	0	0
IKK complex/ELKS	0.075	0.009	-10000	0	-10000	0	0
JUN	0.035	0.066	-10000	0	-10000	0	0
MAP3K7	0.016	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.013	0.11	-10000	0	-0.51	4	4
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.031	0.14	-10000	0	-0.33	34	34
PIK3R1	0.016	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.021	0.13	-10000	0	-0.52	3	3
IL1 beta fragment/IL1R1/IL1RAP	-0.005	0.12	-10000	0	-0.35	25	25
NFKB1	0.016	0	-10000	0	-10000	0	0
MAPK8	0.039	0.043	-10000	0	-10000	0	0
IRAK1	0.027	0.005	-10000	0	-10000	0	0
IL1RN/IL1R1	0.009	0.078	-10000	0	-0.39	12	12
IRAK4	0.016	0	-10000	0	-10000	0	0
PRKCI	0.016	0	-10000	0	-10000	0	0
TRAF6	0.016	0	-10000	0	-10000	0	0
PI3K	0.023	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.023	0.068	-10000	0	-0.38	2	2
CHUK	0.016	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.005	0.12	-10000	0	-0.35	25	25
IL1 beta/IL1R2	-0.041	0.15	-10000	0	-0.34	68	68
IRAK/TRAF6/TAK1/TAB1/TAB2	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.029	0.08	-10000	0	-0.46	4	4
IRAK3	0.001	0.093	-10000	0	-0.58	9	9
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.012	0.11	-10000	0	-0.51	4	4
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.002	0.094	-10000	0	-0.5	1	1
IL1 alpha/IL1R1/IL1RAP	-0.046	0.15	-10000	0	-0.32	78	78
RELA	0.016	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.016	0	-10000	0	-10000	0	0
MYD88	0.016	0	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0.043	0.004	-10000	0	-10000	0	0
IL1RAP	-0.001	0.09	-10000	0	-0.51	11	11
UBE2N	0.016	0	-10000	0	-10000	0	0
IRAK/TRAF6	-0.026	0.072	-10000	0	-0.42	4	4
CASP1	0.002	0.088	-10000	0	-0.58	8	8
IL1RN/IL1R2	-0.03	0.14	-10000	0	-0.38	47	47
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.005	0.11	-10000	0	-0.54	4	4
TMEM189-UBE2V1	0.008	0.008	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.015	0.077	-10000	0	-0.52	1	1
PIK3CA	0.016	0	-10000	0	-10000	0	0
IL1RN	-0.002	0.096	-10000	0	-0.52	12	12
TRAF6/TAK1/TAB1/TAB2	0	0	-10000	0	-10000	0	0
MAP2K6	0.034	0.035	-10000	0	-10000	0	0

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.013	0.039	-10000	0	-0.51	2	2
EPHB2	-0.018	0.13	-10000	0	-0.5	23	23
EFNB1	0.015	0.069	-10000	0	-0.42	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.034	0.1	-10000	0	-0.52	4	4
Ephrin B2/EPHB1-2	-0.016	0.12	-10000	0	-0.29	52	52
neuron projection morphogenesis	-0.039	0.094	-10000	0	-0.5	4	4
Ephrin B1/EPHB1-2/Tiam1	-0.006	0.12	-10000	0	-0.38	12	12
DNM1	0.001	0.093	-10000	0	-0.58	9	9
cell-cell signaling	0	0.001	-10000	0	-10000	0	0
MAP2K4	0.013	0.096	-10000	0	-0.62	8	8
YES1	-0.017	0.13	-10000	0	-0.87	8	8
Ephrin B1/EPHB1-2/NCK2	-0.004	0.12	-10000	0	-0.5	4	4
PI3K	0.014	0.097	-10000	0	-0.62	8	8
mol:GDP	-0.007	0.12	-10000	0	-0.37	12	12
ITGA2B	-0.026	0.14	-10000	0	-0.51	28	28
endothelial cell proliferation	0.018	0.025	-10000	0	-0.3	2	2
FYN	-0.018	0.13	-10000	0	-0.89	8	8
MAP3K7	-0.01	0.099	-10000	0	-0.66	8	8
FGR	-0.017	0.13	-10000	0	-0.88	8	8
TIAM1	0.012	0.044	-10000	0	-0.58	2	2
PIK3R1	0.016	0	-10000	0	-10000	0	0
RGS3	0.016	0	-10000	0	-10000	0	0
cell adhesion	-0.025	0.15	-10000	0	-0.54	12	12
LYN	-0.017	0.13	-10000	0	-0.87	8	8
Ephrin B1/EPHB1-2/Src Family Kinases	-0.018	0.12	-10000	0	-0.81	8	8
Ephrin B1/EPHB1-2	-0.017	0.11	-10000	0	-0.72	8	8
SRC	-0.017	0.13	-10000	0	-0.86	8	8
ITGB3	-0.054	0.19	-10000	0	-0.58	42	42
EPHB1	-0.032	0.16	-10000	0	-0.57	29	29
EPHB4	0.016	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.018	0.025	-10000	0	-0.3	2	2
alphaIIb/beta3 Integrin	-0.057	0.17	-10000	0	-0.41	66	66
BLK	-0.032	0.13	-10000	0	-0.86	8	8
HCK	-0.023	0.14	-10000	0	-0.89	8	8
regulation of stress fiber formation	0.005	0.12	0.5	4	-10000	0	4
MAPK8	0.018	0.1	-10000	0	-0.65	8	8
Ephrin B1/EPHB1-2/RGS3	-0.004	0.12	-10000	0	-0.58	3	3
endothelial cell migration	-0.009	0.085	-10000	0	-0.55	8	8
NCK2	0.016	0	-10000	0	-10000	0	0
PTPN13	-0.009	0.1	-10000	0	-0.69	8	8
regulation of focal adhesion formation	0.005	0.12	0.5	4	-10000	0	4
chemotaxis	0.005	0.12	0.57	3	-10000	0	3
PIK3CA	0.016	0	-10000	0	-10000	0	0
Rac1/GTP	-0.04	0.096	-10000	0	-0.52	4	4
angiogenesis	-0.017	0.11	-10000	0	-0.71	8	8
LCK	-0.019	0.13	-10000	0	-0.86	8	8

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.014	0.028	-10000	0	-0.51	1	1
NFATC1	0.036	0.078	-10000	0	-0.29	17	17
NFATC2	-0.025	0.078	-10000	0	-0.19	43	43
NFATC3	0.01	0.035	-10000	0	-0.42	2	2
YWHAE	0.014	0.031	-10000	0	-0.58	1	1
Calcineurin A alpha-beta B1/CABIN1	-0.046	0.14	-10000	0	-0.44	28	28
Exportin 1/Ran/NUP214	0.014	0.016	-10000	0	-10000	0	0
mol:DAG	-0.003	0.004	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.071	0.12	-10000	0	-0.4	34	34
BCL2/BAX	0.006	0.085	-10000	0	-0.41	14	14
CaM/Ca2+/Calcineurin A alpha-beta B1	0.003	0.01	-10000	0	-10000	0	0
CaM/Ca2+	0.003	0.01	-10000	0	-10000	0	0
BAX	0.016	0	-10000	0	-10000	0	0
MAPK14	0.007	0.008	-10000	0	-10000	0	0
BAD	0.016	0	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.04	0.14	-10000	0	-0.42	28	28
Calcineurin A alpha-beta B1/BCL2	-0.008	0.12	-10000	0	-0.57	14	14
FKBP8	0.016	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.039	0.14	0.41	28	-10000	0	28
KPNB1	0.016	0	-10000	0	-10000	0	0
KPNA2	0.013	0.039	-10000	0	-0.51	2	2
XPO1	0.015	0.001	-10000	0	-10000	0	0
SFN	-0.034	0.15	-10000	0	-0.52	33	33
MAP3K8	0.002	0.054	-10000	0	-0.58	3	3
NFAT4/CK1 alpha	-0.001	0.018	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.13	0.18	-10000	0	-0.38	43	43
CABIN1	-0.046	0.15	-10000	0	-0.45	28	28
CALM1	0.01	0.006	-10000	0	-10000	0	0
RAN	0.015	0.001	-10000	0	-10000	0	0
MAP3K1	0.016	0	-10000	0	-10000	0	0
CAMK4	-0.003	0.1	-10000	0	-0.57	11	11
mol:Ca2+	-0.009	0.009	-10000	0	-10000	0	0
MAPK3	0.016	0	-10000	0	-10000	0	0
YWHAH	0.016	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.006	0.04	-10000	0	-0.36	4	4
YWHAB	0.016	0	-10000	0	-10000	0	0
MAPK8	0.002	0.054	-10000	0	-0.58	3	3
MAPK9	0.016	0	-10000	0	-10000	0	0
YWHAG	0.016	0	-10000	0	-10000	0	0
FKBP1A	0.016	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.029	0.083	-10000	0	-0.31	10	10
PRKCH	0.016	0	-10000	0	-10000	0	0
CABIN1/Cbp/p300	0.01	0.014	-10000	0	-10000	0	0
CASP3	0.007	0.008	-10000	0	-10000	0	0
PIM1	0.016	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.005	0.006	-10000	0	-10000	0	0
apoptosis	-0.005	0.025	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.035	0.038	-10000	0	-0.28	1	1
PRKCB	-0.16	0.27	-10000	0	-0.58	103	103
PRKCE	0.016	0	-10000	0	-10000	0	0
JNK2/NFAT4	0.024	0.031	-10000	0	-0.37	2	2
BAD/BCL-XL	0.022	0.02	-10000	0	-0.36	1	1
PRKCD	0.016	0	-10000	0	-10000	0	0
NUP214	0.015	0.001	-10000	0	-10000	0	0
PRKCZ	0.004	0.045	-10000	0	-0.58	2	2
PRKCA	0.011	0.054	-10000	0	-0.58	3	3
PRKCG	-0.008	0.089	-10000	0	-0.51	11	11
PRKCQ	-0.042	0.18	-10000	0	-0.57	35	35
FKBP38/BCL2	0.006	0.085	-10000	0	-0.41	14	14
EP300	0.009	0.006	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.016	0	-10000	0	-10000	0	0
NFATc/JNK1	0.015	0.08	-10000	0	-10000	0	0
CaM/Ca2+/FKBP38	0.01	0.011	-10000	0	-10000	0	0
FKBP12/FK506	0.012	0	-10000	0	-10000	0	0
CSNK1A1	0.011	0.012	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.001	0.065	-10000	0	-0.36	11	11
NFATc/ERK1	0.043	0.075	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.068	0.12	-10000	0	-0.4	33	33
NR4A1	-0.28	0.3	-10000	0	-0.54	200	200
GSK3B	0.007	0.008	-10000	0	-10000	0	0
positive T cell selection	0.01	0.035	-10000	0	-0.41	2	2
NFAT1/CK1 alpha	-0.035	0.051	-10000	0	-0.29	3	3
RCH1/ KPNB1	0.021	0.028	-10000	0	-0.36	2	2
YWHAQ	0.016	0	-10000	0	-10000	0	0
PRKACA	0.007	0.008	-10000	0	-10000	0	0
AKAP5	0.01	0.055	-10000	0	-0.51	4	4
MEF2D	0.009	0.006	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.016	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.017	0.077	-10000	0	-10000	0	0
CREBBP	0.009	0.006	-10000	0	-10000	0	0
BCL2	-0.008	0.12	-10000	0	-0.58	14	14

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.021	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.016	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.007	0.068	-9999	-0.56	5	5
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.016	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.025	0.023	-9999	-0.21	1	1
response to UV	0	0	-9999	-10000	0	0
YES1	0.016	0	-9999	-10000	0	0
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.016	0	-9999	-10000	0	0
FYN	0.011	0.054	-9999	-0.58	3	3
MAP3K12	0.014	0.031	-9999	-0.58	1	1
FGR	0.014	0.031	-9999	-0.58	1	1
p38 alpha/TAB1	-0.02	0.053	-9999	-0.26	10	10
PRKG1	-0.12	0.25	-9999	-0.58	82	82
DUSP8	-0.026	0.15	-9999	-0.58	25	25
PGK/cGMP/p38 alpha	-0.072	0.12	-9999	-0.38	29	29
apoptosis	-0.02	0.051	-9999	-0.27	7	7
RAL/GTP	0.02	0.017	-9999	-0.3	1	1
LYN	0.016	0	-9999	-10000	0	0
DUSP1	-0.15	0.27	-9999	-0.58	102	102
PAK1	0.014	0.031	-9999	-0.58	1	1
SRC	0.016	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.039	0.016	-9999	-10000	0	0
TRAF6	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0.014	0.028	-9999	-0.51	1	1
RAC1-CDC42/GTP	0.021	0	-9999	-10000	0	0
MAPK11	0.029	0.096	-9999	-0.32	11	11
BLK	-0.054	0.18	-9999	-0.56	42	42
HCK	-0.012	0.12	-9999	-0.56	17	17
MAP2K3	0.016	0	-9999	-10000	0	0
DUSP16	0.016	0	-9999	-10000	0	0
DUSP10	0.01	0.055	-9999	-0.51	4	4
TRAF6/MEKK3	0.02	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.032	0.08	-9999	-0.28	10	10
positive regulation of innate immune response	0.037	0.11	-9999	-0.35	11	11
LCK	0.006	0.073	-9999	-0.55	6	6
p38alpha-beta/MKP7	0.043	0.1	-9999	-0.51	2	2
p38alpha-beta/MKP5	0.041	0.11	-9999	-0.36	8	8
PGK/cGMP	-0.089	0.18	-9999	-0.42	82	82
PAK2	0.016	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.033	0.18	-9999	-0.43	37	37
CDC42	0.016	0	-9999	-10000	0	0
RALB	0.016	0	-9999	-10000	0	0
RALA	0.014	0.028	-9999	-0.51	1	1
PAK3	-0.006	0.085	-9999	-0.51	10	10

×

BARD1 signaling events

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
BARD1/CSTF1	0.012	0.068	-10000	0	-0.41	9	9
ATM	0.016	0	-10000	0	-10000	0	0
UBE2D3	0.016	0	-10000	0	-10000	0	0
PRKDC	0.016	0	-10000	0	-10000	0	0
ATR	0.016	0	-10000	0	-10000	0	0
UBE2L3	0.016	0	-10000	0	-10000	0	0
FANCD2	0.029	0.019	-10000	0	-10000	0	0
protein ubiquitination	-0.043	0.093	-10000	0	-0.3	9	9
XRCC5	0.016	0	-10000	0	-10000	0	0
XRCC6	0.016	0	-10000	0	-10000	0	0
M/R/N Complex	0.032	0	-10000	0	-10000	0	0
MRE11A	0.016	0	-10000	0	-10000	0	0
DNA-PK	0.032	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.045	0.036	-10000	0	-10000	0	0
FANCF	0.012	0.042	-10000	0	-0.54	2	2
BRCA1	0.014	0.028	-10000	0	-0.51	1	1
CCNE1	-0.066	0.19	-10000	0	-0.51	56	56
CDK2/Cyclin E1	-0.036	0.14	-10000	0	-0.36	56	56
FANCG	0.016	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.011	0.071	-10000	0	-0.41	10	10
FANCE	0.016	0	-10000	0	-10000	0	0
FANCC	0.014	0.028	-10000	0	-0.51	1	1
NBN	0.016	0	-10000	0	-10000	0	0
FANCA	-0.02	0.13	-10000	0	-0.51	24	24
DNA repair	-0.023	0.13	-10000	0	-0.4	4	4
BRCA1/BARD1/ubiquitin	0.011	0.071	-10000	0	-0.41	10	10
BARD1/DNA-PK	0.031	0.054	-10000	0	-0.3	9	9
FANCL	0.014	0.028	-10000	0	-0.51	1	1
mRNA polyadenylation	-0.012	0.068	0.41	9	-10000	0	9
BRCA1/BARD1/CTIP/M/R/N Complex	0.04	0.044	-10000	0	-0.23	9	9
BRCA1/BACH1/BARD1/TopBP1	0.021	0.061	-10000	0	-0.34	10	10
BRCA1/BARD1/P53	0.031	0.056	-10000	0	-0.3	9	9
BARD1/CSTF1/BRCA1	0.021	0.061	-10000	0	-0.34	10	10
BRCA1/BACH1	0.014	0.028	-10000	0	-0.51	1	1
BARD1	0	0.093	-10000	0	-0.58	9	9
PCNA	0.014	0.028	-10000	0	-0.51	1	1
BRCA1/BARD1/UbcH5C	0.021	0.061	-10000	0	-0.34	10	10
BRCA1/BARD1/UbcH7	0.021	0.061	-10000	0	-0.34	10	10
BRCA1/BARD1/RAD51/PCNA	-0.072	0.15	-10000	0	-0.36	9	9
BARD1/DNA-PK/P53	0.038	0.051	-10000	0	-10000	0	0
BRCA1/BARD1/Ubiquitin	0.011	0.071	-10000	0	-0.41	10	10
BRCA1/BARD1/CTIP	0.03	0.056	-10000	0	-0.3	10	10
FA complex	0.035	0.043	-10000	0	-10000	0	0
BARD1/EWS	0.012	0.068	-10000	0	-0.41	9	9
RBBP8	0.026	0	-10000	0	-10000	0	0
TP53	0.016	0	-10000	0	-10000	0	0
TOPBP1	0.016	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.029	0.055	0.3	9	-10000	0	9
BRCA1/BARD1	-0.006	0.11	-10000	0	-0.31	9	9
CSTF1	0.016	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0	0.068	-10000	0	-0.42	9	9
CDK2	0.016	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.16	0.25	-10000	0	-0.51	123	123
RAD50	0.016	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.011	0.071	-10000	0	-0.41	10	10
EWSR1	0.016	0	-10000	0	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.016	0	-9999	-10000	0	0
ITGB7	0.009	0.062	-9999	-0.58	4	4
ITGA4	-0.004	0.11	-9999	-0.57	12	12
alpha4/beta7 Integrin	0.004	0.09	-9999	-0.41	16	16
alpha4/beta1 Integrin	0.009	0.078	-9999	-0.41	12	12

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.025	0.02	-9999	-0.36	1	1
BAD/BCL-XL/YWHAZ	0.038	0.016	-9999	-10000	0	0
CDKN1B	0.043	0	-9999	-10000	0	0
CDKN1A	0.042	0.016	-9999	-0.26	1	1
FRAP1	0	0	-9999	-10000	0	0
PRKDC	0.016	0	-9999	-10000	0	0
FOXO3	0.043	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
BAD	0.016	0	-9999	-10000	0	0
AKT3	0.009	0.063	-9999	-0.35	11	11
mol:GTP	0	0	-9999	-10000	0	0
FOXO4	0.042	0.014	-9999	-10000	0	0
AKT1/ASK1	0.041	0	-9999	-10000	0	0
BAD/YWHAZ	0.032	0	-9999	-10000	0	0
RICTOR	0.016	0	-9999	-10000	0	0
RAF1	0.014	0.028	-9999	-0.51	1	1
JNK cascade	0	0	-9999	-10000	0	0
TSC1	0.043	0	-9999	-10000	0	0
YWHAZ	0.016	0	-9999	-10000	0	0
AKT1/RAF1	0.043	0.014	-9999	-10000	0	0
EP300	0.016	0	-9999	-10000	0	0
mol:GDP	0.036	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
TSC2	0.043	0	-9999	-10000	0	0
YWHAQ	0.016	0	-9999	-10000	0	0
TBC1D4	0.028	0	-9999	-10000	0	0
MAP3K5	0.016	0	-9999	-10000	0	0
MAPKAP1	0.016	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.044	0.027	-9999	-10000	0	0
YWHAH	0.016	0	-9999	-10000	0	0
AKT1S1	0.043	0	-9999	-10000	0	0
CASP9	0.043	0	-9999	-10000	0	0
YWHAB	0.016	0	-9999	-10000	0	0
p27Kip1/KPNA1	0.051	0	-9999	-10000	0	0
GBL	0	0	-9999	-10000	0	0
PDK1/Src/Hsp90	0.032	0	-9999	-10000	0	0
YWHAE	0.014	0.031	-9999	-0.58	1	1
SRC	0.016	0	-9999	-10000	0	0
AKT2/p21CIP1	-0.001	0.013	-9999	-10000	0	0
KIAA1303	0	0	-9999	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.022	0	-9999	-10000	0	0
CHUK	0.043	0	-9999	-10000	0	0
BAD/BCL-XL	0.058	0.013	-9999	-10000	0	0
mTORC2	0.02	0	-9999	-10000	0	0
AKT2	0.02	0	-9999	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.061	0.031	-9999	-10000	0	0
PDPK1	0.016	0	-9999	-10000	0	0
MDM2	0.034	0.047	-9999	-10000	0	0
MAPKKK cascade	-0.042	0.014	-9999	-10000	0	0
MDM2/Cbp/p300	0.049	0.044	-9999	-10000	0	0
TSC1/TSC2	0.05	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.047	0.043	-9999	-10000	0	0
glucose import	-0.21	0.15	-9999	-0.3	260	260
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.037	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	-0.21	0.15	-9999	-0.3	260	260
GSK3A	0.043	0	-9999	-10000	0	0
FOXO1	0.043	0	-9999	-10000	0	0
GSK3B	0.043	0	-9999	-10000	0	0
SFN	-0.034	0.15	-9999	-0.52	33	33
G1/S transition of mitotic cell cycle	0.05	0	-9999	-10000	0	0
p27Kip1/14-3-3 family	0.045	0.041	-9999	-0.3	1	1
PRKACA	0.016	0	-9999	-10000	0	0
KPNA1	0.016	0	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
YWHAG	0.016	0	-9999	-10000	0	0
RHEB	0.016	0	-9999	-10000	0	0
CREBBP	0.016	0	-9999	-10000	0	0

×

EPHB forward signaling

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
Ephrin A5/EPHB2	-0.011	0.1	-10000	0	-0.32	34	34
cell-cell adhesion	0.041	0.092	0.46	6	-10000	0	6
Ephrin B/EPHB2/RasGAP	0.01	0.1	-10000	0	-0.51	2	2
ITSN1	0.016	0	-10000	0	-10000	0	0
PIK3CA	0.016	0	-10000	0	-10000	0	0
SHC1	0.014	0.028	-10000	0	-0.51	1	1
Ephrin B1/EPHB3	0.007	0.065	-10000	0	-0.3	15	15
Ephrin B1/EPHB1	-0.009	0.1	-10000	0	-0.35	29	29
HRAS/GDP	-0.027	0.087	-10000	0	-0.49	5	5
Ephrin B/EPHB1/GRB7	-0.013	0.14	-10000	0	-0.58	6	6
Endophilin/SYNJ1	0.009	0.094	-10000	0	-0.48	2	2
KRAS	0.014	0.028	-10000	0	-0.51	1	1
Ephrin B/EPHB1/Src	0.002	0.12	-10000	0	-0.59	5	5
endothelial cell migration	-0.001	0.018	-10000	0	-10000	0	0
GRB2	0.016	0	-10000	0	-10000	0	0
GRB7	-0.013	0.12	-10000	0	-0.52	19	19
PAK1	0.013	0.1	-10000	0	-0.48	2	2
HRAS	0.016	0	-10000	0	-10000	0	0
RRAS	0.007	0.1	-10000	0	-0.51	3	3
DNM1	0.001	0.093	-10000	0	-0.58	9	9
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	0.002	0.12	-10000	0	-0.56	5	5
lamellipodium assembly	-0.041	0.092	-10000	0	-0.46	6	6
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.014	0.094	-10000	0	-0.44	4	4
PIK3R1	0.016	0	-10000	0	-10000	0	0
EPHB2	-0.018	0.13	-10000	0	-0.51	23	23
EPHB3	-0.007	0.11	-10000	0	-0.51	15	15
EPHB1	-0.032	0.16	-10000	0	-0.57	29	29
EPHB4	0.016	0	-10000	0	-10000	0	0
mol:GDP	0.016	0.1	-10000	0	-0.47	5	5
Ephrin B/EPHB2	0.001	0.1	-10000	0	-0.32	13	13
Ephrin B/EPHB3	0.007	0.097	-10000	0	-0.34	13	13
JNK cascade	0.001	0.11	-10000	0	-0.57	1	1
Ephrin B/EPHB1	-0.007	0.12	-10000	0	-0.33	36	36
RAP1/GDP	0.03	0.091	-10000	0	-0.4	5	5
EFNB2	0.013	0.039	-10000	0	-0.51	2	2
EFNB3	-0.016	0.13	-10000	0	-0.55	20	20
EFNB1	0.016	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.018	0.12	-10000	0	-0.3	52	52
RAP1B	0.016	0	-10000	0	-10000	0	0
RAP1A	0.016	0	-10000	0	-10000	0	0
CDC42/GTP	-0.04	0.094	-10000	0	-0.48	6	6
Rap1/GTP	-0.04	0.091	-10000	0	-0.46	6	6
axon guidance	-0.011	0.099	-10000	0	-0.32	34	34
MAPK3	0.03	0.085	-10000	0	-0.38	4	4
MAPK1	0.03	0.085	-10000	0	-0.38	4	4
Rac1/GDP	0.024	0.095	-10000	0	-0.43	5	5
actin cytoskeleton reorganization	-0.029	0.067	-10000	0	-0.37	5	5
CDC42/GDP	0.024	0.095	-10000	0	-0.43	5	5
PI3K	0.035	0.021	-10000	0	-10000	0	0
EFNA5	-0.003	0.1	-10000	0	-0.58	11	11
Ephrin B2/EPHB4	0.019	0.024	-10000	0	-0.3	2	2
Ephrin B/EPHB2/Intersectin/N-WASP	0.02	0.067	-10000	0	-0.38	1	1
CDC42	0.016	0	-10000	0	-10000	0	0
RAS family/GTP	-0.039	0.088	-10000	0	-0.45	6	6
PTK2	0.011	0.027	-10000	0	-10000	0	0
MAP4K4	0.001	0.11	-10000	0	-0.58	1	1
SRC	0.016	0	-10000	0	-10000	0	0
KALRN	0.008	0.065	-10000	0	-0.54	5	5
Intersectin/N-WASP	0.023	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.037	0.1	-10000	0	-0.38	6	6
MAP2K1	0.022	0.089	-10000	0	-0.41	4	4
WASL	0.016	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.006	0.11	-10000	0	-0.3	25	25
cell migration	0.026	0.1	-10000	0	-0.45	4	4
NRAS	0.016	0	-10000	0	-10000	0	0
SYNJ1	0.009	0.095	-10000	0	-0.49	2	2
PXN	0.016	0	-10000	0	-10000	0	0
TF	-0.018	0.13	-10000	0	-0.5	9	9
HRAS/GTP	-0.044	0.099	-10000	0	-0.49	6	6
Ephrin B1/EPHB1-2	-0.016	0.11	-10000	0	-0.29	52	52
cell adhesion mediated by integrin	0.015	0.076	0.29	20	-10000	0	20
RAC1	0.016	0	-10000	0	-10000	0	0
mol:GTP	-0.007	0.13	-10000	0	-0.53	6	6
RAC1-CDC42/GTP	-0.047	0.1	-10000	0	-0.44	12	12
RASA1	0.016	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0.03	0.091	-10000	0	-0.43	4	4
ruffle organization	0.018	0.12	-10000	0	-0.46	6	6
NCK1	0.016	0	-10000	0	-10000	0	0
receptor internalization	0.01	0.1	-10000	0	-0.46	2	2
Ephrin B/EPHB2/KALRN	0.006	0.1	-10000	0	-0.31	15	15
ROCK1	0.017	0.059	-10000	0	-0.27	15	15
RAS family/GDP	-0.027	0.064	-10000	0	-0.38	4	4
Rac1/GTP	-0.043	0.097	-10000	0	-0.49	6	6
Ephrin B/EPHB1/Src/Paxillin	0.009	0.099	-10000	0	-0.27	36	36

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.12	0.2	-9999	-0.65	8	8
RAD9A	0.007	0.067	-9999	-0.51	6	6
AP1	-0.13	0.23	-9999	-0.46	111	111
IFNAR2	0.01	0.009	-9999	-10000	0	0
AKT1	-0.027	0.092	-9999	-0.24	31	31
ER alpha/Oestrogen	-0.067	0.16	-9999	-0.43	61	61
NFX1/SIN3/HDAC complex	0.032	0.029	-9999	-10000	0	0
EGF	-0.02	0.13	-9999	-0.51	22	22
SMG5	0.016	0	-9999	-10000	0	0
SMG6	0.016	0	-9999	-10000	0	0
SP3/HDAC2	0.015	0.014	-9999	-10000	0	0
TERT/c-Abl	-0.13	0.17	-9999	-0.64	6	6
SAP18	0.015	0.002	-9999	-10000	0	0
MRN complex	0.032	0	-9999	-10000	0	0
WT1	-0.061	0.17	-9999	-0.51	46	46
WRN	0.016	0	-9999	-10000	0	0
SP1	0.011	0.01	-9999	-10000	0	0
SP3	0.013	0.004	-9999	-10000	0	0
TERF2IP	0.016	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.12	0.14	-9999	-0.63	4	4
Mad/Max	0.013	0.024	-9999	-0.37	1	1
TERT	-0.13	0.2	-9999	-0.71	6	6
CCND1	-0.12	0.24	-9999	-1	10	10
MAX	0.013	0.004	-9999	-10000	0	0
RBBP7	0.015	0.002	-9999	-10000	0	0
RBBP4	0.015	0.002	-9999	-10000	0	0
TERF2	0.014	0	-9999	-10000	0	0
PTGES3	0.016	0	-9999	-10000	0	0
SIN3A	0.015	0.002	-9999	-10000	0	0
Telomerase/911	0.024	0.039	-9999	-10000	0	0
CDKN1B	-0.022	0.12	-9999	-10000	0	0
RAD1	0.016	0	-9999	-10000	0	0
XRCC5	0.016	0	-9999	-10000	0	0
XRCC6	0.016	0	-9999	-10000	0	0
SAP30	0.015	0.002	-9999	-10000	0	0
TRF2/PARP2	0	0	-9999	-10000	0	0
UBE3A	0.014	0.004	-9999	-10000	0	0
JUN	-0.008	0.11	-9999	-0.58	13	13
E6	-0.002	0.004	-9999	-10000	0	0
HPV-16 E6/E6AP	0.008	0.007	-9999	-10000	0	0
FOS	-0.17	0.27	-9999	-0.58	110	110
IFN-gamma/IRF1	-0.049	0.14	-9999	-0.34	68	68
PARP2	0.016	0	-9999	-10000	0	0
BLM	0.002	0.082	-9999	-0.51	9	9
Telomerase	-0.007	0.062	-9999	-0.41	1	1
IRF1	0.019	0.005	-9999	-10000	0	0
ESR1	-0.087	0.22	-9999	-0.58	61	61
KU/TER	0.023	0	-9999	-10000	0	0
ATM/TRF2	0.024	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.038	0.03	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.036	0.032	-9999	-10000	0	0
HDAC1	0.015	0.002	-9999	-10000	0	0
HDAC2	0.01	0.01	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.029	0.005	-9999	-10000	0	0
ABL1	0.016	0	-9999	-10000	0	0
MXD1	0.012	0.028	-9999	-0.52	1	1
MRE11A	0.016	0	-9999	-10000	0	0
HUS1	0.016	0	-9999	-10000	0	0
RPS6KB1	0.016	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.13	0.16	-9999	-0.65	5	5
NR2F2	0.018	0.033	-9999	-0.58	1	1
MAPK3	0.012	0.011	-9999	-10000	0	0
MAPK1	0.012	0.011	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.017	0.002	-9999	-10000	0	0
NFKB1	0.016	0	-9999	-10000	0	0
HNRNPC	0.016	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0	0	-9999	-10000	0	0
NBN	0.016	0	-9999	-10000	0	0
EGFR	-0.01	0.11	-9999	-0.54	15	15
mol:Oestrogen	-0.002	0.003	-9999	-10000	0	0
EGF/EGFR	-0.026	0.12	-9999	-0.37	37	37
MYC	-0.02	0.13	-9999	-0.58	18	18
IL2	-0.001	0.013	-9999	-10000	0	0
KU	0.023	0	-9999	-10000	0	0
RAD50	0.016	0	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
TGFB1	0.017	0.002	-9999	-10000	0	0
TRF2/BLM	-0.008	0.051	-9999	-0.33	9	9
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.1	0.19	-9999	-0.64	6	6
SP1/HDAC2	0.017	0.016	-9999	-10000	0	0
PINX1	0.016	0	-9999	-10000	0	0
Telomerase/EST1A	-0.12	0.14	-9999	-0.63	4	4
Smad3/Myc	0.014	0.082	-9999	-0.34	18	18
911 complex	0.026	0.041	-9999	-0.29	6	6
IFNG	-0.083	0.2	-9999	-0.5	68	68
Telomerase/PinX1	-0.12	0.14	-9999	-0.63	4	4
Telomerase/AKT1/mTOR/p70S6K	-0.011	0.066	-9999	-10000	0	0
SIN3B	0.015	0.002	-9999	-10000	0	0
YWHAE	0.014	0.031	-9999	-0.58	1	1
Telomerase/EST1B	-0.12	0.14	-9999	-0.63	4	4
response to DNA damage stimulus	0.004	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0	0	-9999	-10000	0	0
TRF2/WRN	0	0	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.12	0.14	-9999	-0.63	4	4
E2F1	-0.11	0.22	-9999	-0.51	81	81
ZNFX1	0.015	0.002	-9999	-10000	0	0
PIF1	-0.029	0.15	-9999	-0.51	30	30
NCL	0.016	0	-9999	-10000	0	0
DKC1	0.016	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	-0.066	0.19	-9999	-0.51	56	56
mol:Halofuginone	0.006	0.001	-9999	-10000	0	0
ITGA1	0.016	0	-9999	-10000	0	0
CDKN1A	0	0.075	-9999	-0.67	1	1
PRL-3/alpha Tubulin	0.023	0	-9999	-10000	0	0
mol:Ca2+	-0.054	0.14	-9999	-0.43	45	45
AGT	-0.059	0.2	-9999	-0.57	45	45
CCNA2	-0.1	0.18	-9999	-0.53	22	22
TUBA1B	0.016	0	-9999	-10000	0	0
EGR1	-0.078	0.19	-9999	-0.41	87	87
CDK2/Cyclin E1	-0.024	0.12	-9999	-0.38	14	14
MAPK3	0.026	0	-9999	-10000	0	0
PRL-2 /Rab GGTase beta	0.023	0	-9999	-10000	0	0
MAPK1	0.026	0	-9999	-10000	0	0
PTP4A1	-0.039	0.14	-9999	-10000	0	0
PTP4A3	0.016	0	-9999	-10000	0	0
PTP4A2	0.016	0	-9999	-10000	0	0
ITGB1	0.026	0	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
RAC1	0.002	0.066	-9999	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0.023	0	-9999	-10000	0	0
PRL-1/ATF-5	-0.031	0.14	-9999	-0.53	1	1
RABGGTA	0.016	0	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
RHOC	0.002	0.066	-9999	-10000	0	0
RHOA	0.002	0.066	-9999	-10000	0	0
cell motility	0.005	0.071	-9999	-10000	0	0
PRL-1/alpha Tubulin	-0.029	0.14	-9999	-10000	0	0
PRL-3/alpha1 Integrin	0.023	0	-9999	-10000	0	0
ROCK1	0.005	0.071	-9999	-10000	0	0
RABGGTB	0.016	0	-9999	-10000	0	0
CDK2	0.016	0	-9999	-10000	0	0
mitosis	-0.039	0.14	-9999	-10000	0	0
ATF5	0.013	0.039	-9999	-0.51	2	2

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.016	0.079	-9999	-0.37	14	14
E-cadherin/beta catenin	0.007	0.082	-9999	-0.41	13	13
CTNNB1	0.016	0	-9999	-10000	0	0
JUP	0.012	0.044	-9999	-0.58	2	2
CDH1	-0.006	0.11	-9999	-0.58	13	13

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.061	0.09	-9999	-0.42	3	3
CRKL	0.026	0.079	-9999	-0.29	3	3
mol:DAG	0.038	0.066	-9999	-0.28	1	1
HRAS	0.054	0.068	-9999	-10000	0	0
MAPK8	0.011	0.092	-9999	-0.34	6	6
RAP1A	0.028	0.077	-9999	-0.29	3	3
GAB1	0.028	0.077	-9999	-0.29	3	3
MAPK14	0.013	0.084	-9999	-0.28	3	3
EPO	-0.028	0.14	-9999	-0.5	30	30
PLCG1	0.039	0.067	-9999	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0.006	0.077	-9999	-0.5	8	8
RAPGEF1	0.016	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.038	0.16	-9999	-0.34	70	70
GAB1/SHC/GRB2/SOS1	-0.017	0.046	-9999	-10000	0	0
EPO/EPOR (dimer)	-0.013	0.12	-9999	-0.35	38	38
IRS2	0.016	0.097	-9999	-0.34	6	6
STAT1	0.044	0.082	-9999	-0.38	3	3
STAT5B	0.042	0.074	-9999	-0.34	3	3
cell proliferation	0.019	0.086	-9999	-0.37	3	3
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.019	0.055	-9999	-0.43	2	2
TEC	0.028	0.077	-9999	-0.29	3	3
SOCS3	-0.047	0.18	-9999	-0.58	38	38
STAT1 (dimer)	0.044	0.081	-9999	-0.37	3	3
JAK2	0.014	0.032	-9999	-0.57	1	1
PIK3R1	0.016	0	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.034	0.086	-9999	-0.3	4	4
EPO/EPOR	-0.013	0.12	-9999	-0.35	38	38
LYN	0.017	0.004	-9999	-10000	0	0
TEC/VAV2	0.036	0.078	-9999	-10000	0	0
elevation of cytosolic calcium ion concentration	0.006	0.077	-9999	-0.5	8	8
SHC1	0.014	0.028	-9999	-0.51	1	1
EPO/EPOR (dimer)/LYN	0.01	0.097	-9999	-0.27	38	38
mol:IP3	0.038	0.066	-9999	-0.28	1	1
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.025	0.1	-9999	-0.4	5	5
SH2B3	0.016	0.007	-9999	-10000	0	0
NFKB1	0.013	0.084	-9999	-0.28	3	3
EPO/EPOR (dimer)/JAK2/SOCS3	-0.037	0.084	-9999	-0.31	13	13
PTPN6	0.019	0.08	-9999	-0.3	4	4
TEC/VAV2/GRB2	0.042	0.076	-9999	-10000	0	0
EPOR	0.006	0.077	-9999	-0.5	8	8
INPP5D	0.004	0.082	-9999	-0.58	7	7
mol:GDP	-0.017	0.046	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
PLCG2	0.01	0.057	-9999	-0.52	4	4
CRKL/CBL/C3G	0.042	0.075	-9999	-10000	0	0
VAV2	0.026	0.079	-9999	-0.29	3	3
CBL	0.028	0.077	-9999	-0.29	3	3
SHC/Grb2/SOS1	-0.019	0.05	-9999	-10000	0	0
STAT5A	0.041	0.076	-9999	-0.32	4	4
GRB2	0.016	0	-9999	-10000	0	0
STAT5 (dimer)	0.057	0.096	-9999	-0.47	3	3
LYN/PLCgamma2	0.02	0.042	-9999	-0.37	4	4
PTPN11	0.016	0	-9999	-10000	0	0
BTK	0.009	0.11	-9999	-0.36	8	8
BCL2	0.039	0.19	-9999	-0.9	14	14

×

IFN-gamma 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0	0.095	-9999	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
CRKL	0.013	0.039	-9999	-0.51	2	2
STAT1 (dimer)/Cbp/p300	0.037	0.092	-9999	-0.36	4	4
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.005	0.02	-9999	-0.34	1	1
antigen processing and presentation of peptide antigen via MHC class I	-0.032	0.063	-9999	-0.31	7	7
CaM/Ca2+	-0.033	0.068	-9999	-10000	0	0
RAP1A	0.016	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	0.007	0.099	-9999	-0.42	4	4
AKT1	0.023	0.081	-9999	-10000	0	0
MAP2K1	0.019	0.086	-9999	-10000	0	0
MAP3K11	0.008	0.089	-9999	-10000	0	0
IFNGR1	0.014	0.008	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.15	0.19	-9999	-0.41	118	118
Rap1/GTP	-0.023	0.048	-9999	-10000	0	0
CRKL/C3G	0.021	0.028	-9999	-0.36	2	2
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.004	0.1	-9999	-10000	0	0
CEBPB	0.056	0.085	-9999	-0.37	3	3
STAT3	0.016	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.007	0.095	-9999	-10000	0	0
STAT1	0.006	0.098	-9999	-0.42	4	4
CALM1	0.016	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.084	0.2	-9999	-0.5	68	68
PIK3CA	0.016	0	-9999	-10000	0	0
STAT1 (dimer)/PIAS1	0.015	0.094	-9999	-0.4	4	4
CEBPB/PTGES2/Cbp/p300	-0.008	0.024	-9999	-10000	0	0
mol:Ca2+	-0.002	0.093	-9999	-10000	0	0
MAPK3	0.036	0.076	-9999	-10000	0	0
STAT1 (dimer)	-0.04	0.086	-9999	-0.46	6	6
MAPK1	0.036	0.076	-9999	-10000	0	0
JAK2	0.012	0.032	-9999	-0.57	1	1
PIK3R1	0.016	0	-9999	-10000	0	0
JAK1	0.014	0.008	-9999	-10000	0	0
CAMK2D	0.014	0.031	-9999	-0.58	1	1
DAPK1	0.055	0.087	-9999	-0.62	3	3
SMAD7	0.018	0.061	-9999	-0.35	1	1
CBL/CRKL/C3G	0.021	0.086	-9999	-0.39	1	1
PI3K	-0.031	0.063	-9999	-10000	0	0
IFNG	-0.084	0.2	-9999	-0.5	68	68
apoptosis	0.035	0.068	-9999	-0.44	3	3
CAMK2G	0.016	0	-9999	-10000	0	0
STAT3 (dimer)	0.016	0	-9999	-10000	0	0
CAMK2A	-0.18	0.28	-9999	-0.58	118	118
CAMK2B	-0.044	0.16	-9999	-0.51	40	40
FRAP1	0.023	0.077	-9999	-10000	0	0
PRKCD	0.024	0.083	-9999	-10000	0	0
RAP1B	0.016	0	-9999	-10000	0	0
negative regulation of cell growth	-0.032	0.063	-9999	-0.31	7	7
PTPN2	0.016	0	-9999	-10000	0	0
EP300	0.016	0	-9999	-10000	0	0
IRF1	0.051	0.079	-9999	-10000	0	0
STAT1 (dimer)/PIASy	0.011	0.094	-9999	-0.4	4	4
SOCS1	0.006	0.021	-9999	-10000	0	0
mol:GDP	-0.029	0.059	-9999	-0.37	1	1
CASP1	0.015	0.073	-9999	-0.29	9	9
PTGES2	0.016	0	-9999	-10000	0	0
IRF9	0.055	0.035	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.03	0.062	-9999	-10000	0	0
RAP1/GDP	-0.023	0.049	-9999	-10000	0	0
CBL	0.007	0.089	-9999	-10000	0	0
MAP3K1	0.008	0.089	-9999	-10000	0	0
PIAS1	0.016	0	-9999	-10000	0	0
PIAS4	0.015	0	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.032	0.063	-9999	-0.31	7	7
PTPN11	-0.002	0.093	-9999	-10000	0	0
CREBBP	0.016	0	-9999	-10000	0	0
RAPGEF1	0.016	0	-9999	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.019	0.081	-9999	-0.36	15	15
CRKL	0.013	0.039	-9999	-0.51	2	2
Rac1/GDP	0.012	0	-9999	-10000	0	0
DOCK1	0.014	0.031	-9999	-0.58	1	1
ITGA4	-0.004	0.11	-9999	-0.57	12	12
alpha4/beta7 Integrin/MAdCAM1	0.014	0.092	-9999	-0.34	15	15
EPO	-0.031	0.14	-9999	-0.51	30	30
alpha4/beta7 Integrin	0.004	0.09	-9999	-0.41	16	16
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin	0.009	0.078	-9999	-0.41	12	12
EPO/EPOR (dimer)	-0.019	0.12	-9999	-0.36	38	38
lamellipodium assembly	0.002	0.012	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
PI3K	0.023	0	-9999	-10000	0	0
ARF6	0.016	0	-9999	-10000	0	0
JAK2	0.009	0.08	-9999	-0.3	12	12
PXN	0.016	0	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
MADCAM1	-0.004	0.094	-9999	-0.51	12	12
cell adhesion	0.013	0.091	-9999	-0.34	15	15
CRKL/CBL	0.021	0.028	-9999	-0.36	2	2
ITGB1	0.016	0	-9999	-10000	0	0
SRC	0.011	0.11	-9999	-0.39	21	21
ITGB7	0.009	0.062	-9999	-0.58	4	4
RAC1	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.001	0.12	-9999	-0.42	24	24
p130Cas/Crk/Dock1	0.035	0.097	-9999	-0.51	6	6
VCAM1	-0.014	0.13	-9999	-0.57	18	18
RHOA	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.029	0.061	-9999	-0.3	11	11
BCAR1	0.02	0.1	-9999	-0.57	6	6
EPOR	0.004	0.077	-9999	-0.51	8	8
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.016	0	-9999	-10000	0	0
GIT1	0.016	0	-9999	-10000	0	0
Rac1/GTP	0.002	0.012	-9999	-10000	0	0

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	0.026	0.053	-10000	0	-0.24	13	13
epithelial cell differentiation	-0.01	0.053	-10000	0	-0.28	13	13
CYFIP2	-0.001	0.098	-10000	0	-0.58	10	10
ENAH	0.06	0.056	-10000	0	-0.33	1	1
EGFR	-0.008	0.11	-10000	0	-0.54	15	15
EPHA2	0.011	0.054	-10000	0	-0.58	3	3
MYO6	0.032	0.058	-10000	0	-10000	0	0
CTNNB1	0.016	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.021	0.062	-10000	0	-0.34	10	10
AQP5	-0.013	0.047	-10000	0	-0.35	1	1
CTNND1	0.016	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.032	0.057	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.018	0.086	-10000	0	-0.5	2	2
EGF	-0.018	0.12	-10000	0	-0.51	22	22
NCKAP1	0.016	0	-10000	0	-10000	0	0
AQP3	-0.093	0.2	-10000	0	-0.49	66	66
cortical microtubule organization	-0.01	0.053	-10000	0	-0.28	13	13
GO:0000145	0.031	0.054	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.025	0.061	-10000	0	-0.29	13	13
MLLT4	0.016	0	-10000	0	-10000	0	0
ARF6/GDP	-0.013	0.052	-10000	0	-0.46	1	1
ARF6	0.016	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.03	0.055	-10000	0	-0.3	3	3
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.045	0.056	-10000	0	-10000	0	0
PVRL2	0.016	0	-10000	0	-10000	0	0
ZYX	0.032	0.06	-10000	0	-10000	0	0
ARF6/GTP	-0.008	0.043	-10000	0	-10000	0	0
CDH1	-0.006	0.11	-10000	0	-0.58	13	13
EGFR/EGFR/EGF/EGF	-0.032	0.085	-10000	0	-0.51	3	3
RhoA/GDP	-0.01	0.049	-10000	0	-10000	0	0
actin cytoskeleton organization	0.038	0.058	-10000	0	-10000	0	0
IGF-1R heterotetramer	0.011	0.054	-10000	0	-0.57	3	3
GIT1	0.016	0	-10000	0	-10000	0	0
IGF1R	0.011	0.054	-10000	0	-0.58	3	3
IGF1	-0.25	0.29	-10000	0	-0.58	159	159
DIAPH1	-0.015	0.097	-10000	0	-0.58	10	10
Wnt receptor signaling pathway	0.01	0.053	0.28	13	-10000	0	13
RHOA	0.016	0	-10000	0	-10000	0	0
RhoA/GTP	-0.014	0.053	-10000	0	-0.46	1	1
CTNNA1	0.016	0	-10000	0	-10000	0	0
VCL	0.038	0.059	-10000	0	-10000	0	0
EFNA1	0.002	0.082	-10000	0	-0.51	9	9
LPP	0.04	0.055	-10000	0	-10000	0	0
Ephrin A1/EPHA2	-0.016	0.063	-10000	0	-0.54	1	1
SEC6/SEC8	-0.008	0.041	-10000	0	-10000	0	0
MGAT3	0.018	0.087	-10000	0	-0.52	2	2
HGF/MET	-0.069	0.11	-10000	0	-0.49	2	2
HGF	-0.12	0.25	-10000	0	-0.57	85	85
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.026	0.053	-10000	0	-0.25	13	13
actin cable formation	0.077	0.054	-10000	0	-0.26	1	1
KIAA1543	0.031	0.096	-10000	0	-0.53	8	8
KIFC3	0.032	0.058	-10000	0	-10000	0	0
NCK1	0.016	0	-10000	0	-10000	0	0
EXOC3	0.016	0	-10000	0	-10000	0	0
ACTN1	0.032	0.058	-10000	0	-10000	0	0
NCK1/GIT1	0.023	0	-10000	0	-10000	0	0
mol:GDP	-0.01	0.053	-10000	0	-0.28	13	13
EXOC4	0.016	0	-10000	0	-10000	0	0
STX4	0.032	0.058	-10000	0	-10000	0	0
PIP5K1C	0.032	0.058	-10000	0	-10000	0	0
LIMA1	0.016	0	-10000	0	-10000	0	0
ABI1	0.016	0	-10000	0	-10000	0	0
ROCK1	0.055	0.063	-10000	0	-0.4	1	1
adherens junction assembly	0.049	0.095	-10000	0	-0.51	8	8
IGF-1R heterotetramer/IGF1	-0.12	0.13	-10000	0	-0.54	5	5
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.023	0	-10000	0	-10000	0	0
MET	0.014	0.028	-10000	0	-0.51	1	1
PLEKHA7	0.032	0.064	-10000	0	-0.56	1	1
mol:GTP	0.029	0.055	-10000	0	-0.3	3	3
establishment of epithelial cell apical/basal polarity	0.061	0.052	-10000	0	-10000	0	0
cortical actin cytoskeleton stabilization	0.026	0.053	-10000	0	-0.24	13	13
regulation of cell-cell adhesion	0.038	0.058	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.026	0.053	-10000	0	-0.25	13	13

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.42	0.26	-10000	0	-0.58	260	260
CLTC	0.037	0.009	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.03	0.011	-10000	0	-10000	0	0
Dynamin 2/GTP	0.028	0.015	-10000	0	-0.26	1	1
EXOC4	0.016	0	-10000	0	-10000	0	0
CD59	0.033	0.008	-10000	0	-10000	0	0
CPE	0.008	0.07	-10000	0	-0.35	13	13
CTNNB1	0.016	0	-10000	0	-10000	0	0
membrane fusion	0.03	0.012	-10000	0	-10000	0	0
CTNND1	0.036	0.014	-10000	0	-10000	0	0
DNM2	0.016	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.037	0.008	-10000	0	-10000	0	0
TSHR	0.013	0.041	-10000	0	-0.3	6	6
INS	0.014	0.003	-10000	0	-10000	0	0
BIN1	-0.062	0.2	-10000	0	-0.58	47	47
mol:Choline	0.03	0.012	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.021	0.017	-10000	0	-0.3	1	1
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.016	0	-10000	0	-10000	0	0
mol:Ca2+	0.027	0.015	-10000	0	-0.26	1	1
JUP	0.032	0.019	-10000	0	-10000	0	0
ASAP2/amphiphysin II	-0.015	0.12	-10000	0	-0.31	47	47
ARF6/GTP	0.012	0	-10000	0	-10000	0	0
CDH1	0.025	0.044	-10000	0	-10000	0	0
clathrin-independent pinocytosis	0.012	0	-10000	0	-10000	0	0
MAPK8IP3	0.008	0.063	-10000	0	-0.52	5	5
positive regulation of endocytosis	0.012	0	-10000	0	-10000	0	0
EXOC2	0.016	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.05	0	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.016	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.005	0.025	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.022	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.017	0.039	-10000	0	-0.31	5	5
ACAP1	0.023	0.029	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	-0.059	0.11	-10000	0	-0.28	2	2
clathrin heavy chain/ACAP1	0.041	0.013	-10000	0	-10000	0	0
JIP4/KLC1	0.03	0	-10000	0	-10000	0	0
EXOC1	0.016	0	-10000	0	-10000	0	0
exocyst	0.05	0	-10000	0	-10000	0	0
RALA/GTP	0.011	0.02	-10000	0	-0.37	1	1
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.021	0	-10000	0	-10000	0	0
receptor recycling	0.012	0	-10000	0	-10000	0	0
CTNNA1	0.036	0.014	-10000	0	-10000	0	0
NME1	0.021	0.017	-10000	0	-0.3	1	1
clathrin coat assembly	0.037	0.009	-10000	0	-10000	0	0
IL2RA	0.016	0.056	-10000	0	-10000	0	0
VAMP3	0.022	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.18	0.11	-10000	0	-0.28	16	16
EXOC6	0.016	0	-10000	0	-10000	0	0
PLD1	0.025	0.017	-10000	0	-0.28	1	1
PLD2	0.026	0.006	-10000	0	-10000	0	0
EXOC5	0.016	0	-10000	0	-10000	0	0
PIP5K1C	0.037	0.008	-10000	0	-10000	0	0
SDC1	0.03	0.028	-10000	0	-10000	0	0
ARF6/GDP	0.02	0.017	-10000	0	-0.3	1	1
EXOC7	0.016	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.005	0.025	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.03	0.012	-10000	0	-10000	0	0
endocytosis	0.016	0.12	0.31	47	-10000	0	47
SCAMP2	0.016	0	-10000	0	-10000	0	0
ADRB2	0.008	0.098	-10000	0	-0.26	42	42
EXOC3	0.016	0	-10000	0	-10000	0	0
ASAP2	0.016	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.029	0.015	-10000	0	-0.26	1	1
KLC1	0.016	0	-10000	0	-10000	0	0
AVPR2	0.014	0.09	-10000	0	-0.26	34	34
RALA	0.014	0.028	-10000	0	-0.51	1	1
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.004	0.021	-10000	0	-10000	0	0

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.13	0.13	-9999	-0.55	3	3
TC10/GTP	-0.12	0.12	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	0.027	0.049	-9999	-0.32	7	7
HRAS	0.016	0	-9999	-10000	0	0
APS homodimer	0.008	0.061	-9999	-0.51	5	5
GRB14	-0.048	0.17	-9999	-0.51	43	43
FOXO3	-0.025	0.11	-9999	-0.59	13	13
AKT1	0.024	0.085	-9999	-10000	0	0
INSR	0.017	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0.042	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.009	0.062	-9999	-0.58	4	4
SORBS1	-0.26	0.3	-9999	-0.58	165	165
CRK	0.016	0	-9999	-10000	0	0
PTPN1	0.04	0	-9999	-10000	0	0
CAV1	0.01	0.091	-9999	-0.34	21	21
CBL/APS/CAP/Crk-II/C3G	-0.11	0.16	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/NCK2	0.027	0.049	-9999	-0.32	7	7
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.005	0.038	-9999	-0.27	7	7
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.04	0.034	-9999	-10000	0	0
RPS6KB1	0.032	0.081	-9999	-10000	0	0
PARD6A	0.014	0.031	-9999	-0.58	1	1
CBL	0.016	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0.001	0.012	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.022	0.056	-9999	-10000	0	0
HRAS/GTP	-0.009	0.044	-9999	-10000	0	0
Insulin Receptor	0.017	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.034	0.048	-9999	-10000	0	0
PRKCI	-0.007	0.028	-9999	-0.47	1	1
Insulin Receptor/Insulin/GRB14/PDK1	-0.029	0.071	-9999	-10000	0	0
SHC1	0.014	0.028	-9999	-0.51	1	1
negative regulation of MAPKKK cascade	0.001	0.01	-9999	-10000	0	0
PI3K	-0.005	0.038	-9999	-0.27	7	7
NCK2	0.016	0	-9999	-10000	0	0
RHOQ	0.016	0	-9999	-10000	0	0
mol:H2O2	0	0	-9999	-10000	0	0
HRAS/GDP	0.012	0	-9999	-10000	0	0
AKT2	0.024	0.085	-9999	-10000	0	0
PRKCZ	-0.01	0.046	-9999	-0.48	3	3
SH2B2	0.008	0.061	-9999	-0.51	5	5
SHC/SHIP	0.027	0.062	-9999	-0.27	14	14
F2RL2	-0.024	0.14	-9999	-0.54	25	25
TRIP10	0.014	0.031	-9999	-0.58	1	1
Insulin Receptor/Insulin/Shc	0.023	0.016	-9999	-0.28	1	1
TC10/GTP/CIP4/Exocyst	0.02	0.02	-9999	-0.35	1	1
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.04	0.015	-9999	-10000	0	0
RAPGEF1	0.016	0	-9999	-10000	0	0
RASA1	0.016	0	-9999	-10000	0	0
NCK1	0.016	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	-0.12	0.17	-9999	-0.3	165	165
TC10/GDP	0.012	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.029	0.04	-9999	-0.31	5	5
INPP5D	0.019	0.064	-9999	-0.3	14	14
SOS1	0.016	0	-9999	-10000	0	0
SGK1	-0.034	0.17	-9999	-0.9	13	13
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.016	0	-9999	-10000	0	0
IRS1	0.004	0.082	-9999	-0.58	7	7
p62DOK/RasGAP	0.001	0.01	-9999	-10000	0	0
INS	0.004	0	-9999	-10000	0	0
mol:PI-3-4-P2	0.019	0.063	-9999	-0.29	14	14
GRB2	0.016	0	-9999	-10000	0	0
EIF4EBP1	0.021	0.094	-9999	-0.39	2	2
PTPRA	0.017	0	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
TC10/GTP/CIP4	0.02	0.02	-9999	-0.35	1	1
PDPK1	0.016	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.033	0.04	-9999	-0.24	7	7
Insulin Receptor/Insulin/IRS1	0.017	0.049	-9999	-0.33	7	7
Insulin Receptor/Insulin/IRS3	0.016	0	-9999	-10000	0	0
Par3/Par6	0.014	0.08	-9999	-10000	0	0

×

PDGFR-beta 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.001	0.11	-9999	-0.52	9	9
PDGFB-D/PDGFRB/SLAP	-0.003	0.12	-9999	-0.52	17	17
PDGFB-D/PDGFRB/APS/CBL	0.017	0.069	-9999	-0.32	14	14
AKT1	0.049	0.066	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0	0.12	-9999	-0.56	9	9
PIK3CA	0.016	0	-9999	-10000	0	0
FGR	-0.01	0.066	-9999	-0.39	10	10
mol:Ca2+	0.016	0.1	-9999	-0.58	9	9
MYC	0.002	0.2	-9999	-0.75	22	22
SHC1	0.014	0.028	-9999	-0.51	1	1
HRAS/GDP	0.034	0.05	-9999	-10000	0	0
LRP1/PDGFRB/PDGFB	0.017	0.07	-9999	-0.34	13	13
GRB10	0.009	0.062	-9999	-0.58	4	4
PTPN11	0.016	0	-9999	-10000	0	0
GO:0007205	0.015	0.1	-9999	-0.59	9	9
PTEN	0.016	0	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
GRB7	-0.013	0.12	-9999	-0.52	19	19
PDGFB-D/PDGFRB/SHP2	0.012	0.069	-9999	-0.41	9	9
PDGFB-D/PDGFRB/GRB10	0.007	0.082	-9999	-0.41	13	13
cell cycle arrest	-0.003	0.12	-9999	-0.52	17	17
HRAS	0.016	0	-9999	-10000	0	0
HIF1A	0.054	0.062	-9999	-10000	0	0
GAB1	0.012	0.11	-9999	-0.56	9	9
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.016	0.1	-9999	-0.51	9	9
PDGFB-D/PDGFRB	0.019	0.062	-9999	-0.36	9	9
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.012	0.069	-9999	-0.41	9	9
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.033	0.093	-9999	-0.48	9	9
positive regulation of MAPKKK cascade	0.012	0.068	-9999	-0.41	9	9
PIK3R1	0.016	0	-9999	-10000	0	0
mol:IP3	0.015	0.1	-9999	-0.59	9	9
E5	0	0.001	-9999	-10000	0	0
CSK	0.015	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.009	0.11	-9999	-0.39	28	28
SHB	0.016	0	-9999	-10000	0	0
BLK	-0.056	0.16	-9999	-0.52	37	37
PTPN2	0.015	0.004	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.012	0.069	-9999	-0.41	9	9
BCAR1	0.016	0	-9999	-10000	0	0
VAV2	0.012	0.12	-9999	-0.59	9	9
CBL	0.016	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.011	0.077	-9999	-0.45	9	9
LCK	-0.015	0.094	-9999	-0.47	12	12
PDGFRB	0.001	0.094	-9999	-0.58	9	9
ACP1	0.016	0	-9999	-10000	0	0
HCK	-0.029	0.15	-9999	-0.64	17	17
ABL1	0.013	0.094	-9999	-0.5	9	9
PDGFB-D/PDGFRB/CBL	0.01	0.12	-9999	-0.63	9	9
PTPN1	0.015	0.004	-9999	-10000	0	0
SNX15	0.016	0	-9999	-10000	0	0
STAT3	0.016	0	-9999	-10000	0	0
STAT1	0.01	0.055	-9999	-0.51	4	4
cell proliferation	0.007	0.18	-9999	-0.65	23	23
SLA	-0.006	0.11	-9999	-0.58	13	13
actin cytoskeleton reorganization	0.049	0.049	-9999	-10000	0	0
SRC	-0.007	0.06	-9999	-0.37	9	9
PI3K	-0.015	0.053	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	0.003	0.096	-9999	-0.32	29	29
SH2B2	0.008	0.061	-9999	-0.51	5	5
PLCgamma1/SPHK1	-0.001	0.12	-9999	-0.58	9	9
LYN	-0.007	0.06	-9999	-0.37	9	9
LRP1	0.011	0.054	-9999	-0.58	3	3
SOS1	0.016	0	-9999	-10000	0	0
STAT5B	0.016	0	-9999	-10000	0	0
STAT5A	0.014	0.031	-9999	-0.58	1	1
NCK1-2/p130 Cas	-0.001	0.045	-9999	-10000	0	0
SPHK1	-0.053	0.18	-9999	-0.5	47	47
EDG1	0	0.002	-9999	-10000	0	0
mol:DAG	0.015	0.1	-9999	-0.59	9	9
PLCG1	0.015	0.11	-9999	-0.61	9	9
NHERF/PDGFRB	0.004	0.092	-9999	-0.31	28	28
YES1	-0.008	0.06	-9999	-0.37	9	9
cell migration	0.001	0.091	-9999	-0.31	28	28
SHC/Grb2/SOS1	-0.002	0.046	-9999	-10000	0	0
SLC9A3R2	0.016	0	-9999	-10000	0	0
SLC9A3R1	-0.012	0.12	-9999	-0.51	19	19
NHERF1-2/PDGFRB/PTEN	0.014	0.084	-9999	-0.3	9	9
FYN	-0.012	0.074	-9999	-0.4	12	12
DOK1	0.027	0.057	-9999	-0.31	9	9
HRAS/GTP	0.012	0	-9999	-10000	0	0
PDGFB	0.014	0.028	-9999	-0.51	1	1
RAC1	0.016	0.14	-9999	-0.46	26	26
PRKCD	0.029	0.055	-9999	-0.31	9	9
FER	0.027	0.061	-9999	-0.31	11	11
MAPKKK cascade	-0.007	0.042	-9999	-10000	0	0
RASA1	0.029	0.055	-9999	-0.31	9	9
NCK1	0.016	0	-9999	-10000	0	0
NCK2	0.016	0	-9999	-10000	0	0
p62DOK/Csk	0.036	0.052	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHB	0.012	0.069	-9999	-0.41	9	9
chemotaxis	0.013	0.092	-9999	-0.48	9	9
STAT1-3-5/STAT1-3-5	-0.009	0.045	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0	0.069	-9999	-0.43	9	9
PTPRJ	0.014	0.031	-9999	-0.58	1	1

×

TRAIL 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
TNFSF10	-0.009	0.11	-10000	0	-0.51	17	17
positive regulation of NF-kappaB transcription factor activity	0	0.092	-10000	0	-0.37	21	21
MAP2K4	0.047	0.032	-10000	0	-10000	0	0
IKBKB	0.016	0	-10000	0	-10000	0	0
TNFRSF10B	0.016	0	-10000	0	-10000	0	0
TNFRSF10A	0.014	0.031	-10000	0	-0.58	1	1
SMPD1	0.016	0.034	-10000	0	-10000	0	0
IKBKG	0.016	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.009	0.062	-10000	0	-0.58	4	4
TRAIL/TRAILR2	0.005	0.081	-10000	0	-0.36	17	17
TRAIL/TRAILR3	-0.004	0.099	-10000	0	-0.36	25	25
TRAIL/TRAILR1	0.004	0.084	-10000	0	-0.36	18	18
TRAIL/TRAILR4	0	0.092	-10000	0	-0.37	21	21
TRAIL/TRAILR1/DAP3/GTP	0.015	0.065	-10000	0	-0.27	18	18
IKK complex	-0.005	0.02	-10000	0	-10000	0	0
RIPK1	0.016	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.012	0	-10000	0	-10000	0	0
MAPK3	0.008	0.081	-10000	0	-0.36	17	17
MAP3K1	0.04	0.034	-10000	0	-10000	0	0
TRAILR4 (trimer)	0.009	0.062	-10000	0	-0.57	4	4
TRADD	0.016	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.014	0.031	-10000	0	-0.57	1	1
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.033	0.04	-10000	0	-10000	0	0
CFLAR	0.016	0	-10000	0	-10000	0	0
MAPK1	0.008	0.081	-10000	0	-0.36	17	17
TRAIL/TRAILR1/FADD/TRADD/RIP	0.028	0.07	-10000	0	-10000	0	0
mol:ceramide	0.016	0.033	-10000	0	-10000	0	0
FADD	0.007	0.067	-10000	0	-0.51	6	6
MAPK8	0.051	0.041	-10000	0	-10000	0	0
TRAF2	0.016	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.003	0.082	-10000	0	-0.54	8	8
CHUK	0.016	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	0.01	0.081	-10000	0	-0.29	24	24
DAP3	0.016	0	-10000	0	-10000	0	0
CASP10	-0.011	0.06	0.27	4	-10000	0	4
JNK cascade	0	0.092	-10000	0	-0.37	21	21
TRAIL (trimer)	-0.009	0.11	-10000	0	-0.51	17	17
TNFRSF10C	0.003	0.083	-10000	0	-0.54	8	8
TRAIL/TRAILR1/DAP3/GTP/FADD	0.018	0.07	-10000	0	-0.24	24	24
TRAIL/TRAILR2/FADD	0.011	0.079	-10000	0	-0.29	23	23
cell death	0.016	0.033	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.034	0.037	-10000	0	-10000	0	0
TRAILR2 (trimer)	0.016	0	-10000	0	-10000	0	0
CASP8	0.004	0.021	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.029	0.068	-10000	0	-10000	0	0

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.024	0.029	-10000	0	-0.36	2	2
MAP4K4	0.036	0.061	-10000	0	-10000	0	0
BAG4	0.016	0	-10000	0	-10000	0	0
PKC zeta/ceramide	-0.004	0.03	-10000	0	-0.32	2	2
NFKBIA	0.016	0	-10000	0	-10000	0	0
BIRC3	-0.024	0.15	-10000	0	-0.57	24	24
BAX	0.002	0.01	-10000	0	-10000	0	0
RIPK1	0.016	0	-10000	0	-10000	0	0
AKT1	0.022	0.006	-10000	0	-10000	0	0
BAD	-0.004	0.019	-10000	0	-10000	0	0
SMPD1	0.025	0.031	-10000	0	-10000	0	0
RB1	-0.004	0.019	0.14	2	-10000	0	2
FADD/Caspase 8	0.044	0.066	-10000	0	-0.28	2	2
MAP2K4	0.004	0.018	-10000	0	-10000	0	0
NSMAF	0.016	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.004	0.024	-10000	0	-0.31	1	1
EGF	-0.018	0.12	-10000	0	-0.51	22	22
mol:ceramide	-0.015	0.02	0.14	2	-10000	0	2
MADD	0.016	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.025	0.02	-10000	0	-0.36	1	1
ASAH1	0.016	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.005	0.019	0.14	2	-10000	0	2
cell proliferation	-0.088	0.13	-10000	0	-0.26	14	14
BID	0.03	0.042	-10000	0	-10000	0	0
MAP3K1	-0.004	0.019	0.14	2	-10000	0	2
EIF2A	0.012	0.017	-10000	0	-10000	0	0
TRADD	0.016	0	-10000	0	-10000	0	0
CRADD	0.016	0	-10000	0	-10000	0	0
MAPK3	0.016	0.023	-10000	0	-0.28	1	1
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.016	0.023	-10000	0	-0.28	1	1
Cathepsin D/ceramide	-0.003	0.019	-10000	0	-10000	0	0
FADD	0.033	0.069	-10000	0	-0.32	2	2
KSR1	-0.004	0.019	0.14	2	-10000	0	2
MAPK8	0.007	0.034	-10000	0	-0.23	5	5
PRKRA	-0.004	0.019	0.14	2	-10000	0	2
PDGFA	0.014	0.028	-10000	0	-0.51	1	1
TRAF2	0.016	0	-10000	0	-10000	0	0
IGF1	-0.25	0.29	-10000	0	-0.58	159	159
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.014	0.02	0.14	2	-10000	0	2
CTSD	0.016	0	-10000	0	-10000	0	0
regulation of nitric oxide biosynthetic process	0.023	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.093	0.14	-10000	0	-0.29	10	10
PRKCD	0.016	0	-10000	0	-10000	0	0
PRKCZ	0.012	0.044	-10000	0	-0.58	2	2
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.025	0.02	-10000	0	-0.36	1	1
RelA/NF kappa B1	0.023	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.014	0.031	-10000	0	-0.58	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.03	0.062	-10000	0	-10000	0	0
TNFR1A/BAG4/TNF-alpha	0.016	0.069	-10000	0	-0.29	17	17
mol:Sphingosine-1-phosphate	0.024	0.028	-10000	0	-0.36	2	2
MAP2K1	0.012	0.023	-10000	0	-0.29	1	1
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.016	0	-10000	0	-10000	0	0
CYCS	0.006	0.035	0.17	14	-10000	0	14
TNFRSF1A	0.016	0	-10000	0	-10000	0	0
NFKB1	0.016	0	-10000	0	-10000	0	0
TNFR1A/BAG4	0.023	0	-10000	0	-10000	0	0
EIF2AK2	0.004	0.018	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	0.016	0.069	-10000	0	-0.29	17	17
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.04	0.038	-10000	0	-10000	0	0
MAP2K2	0.012	0.023	-10000	0	-0.29	1	1
SMPD3	0.027	0.035	-10000	0	-10000	0	0
TNF	-0.009	0.11	-10000	0	-0.51	17	17
PKC zeta/PAR4	0.019	0.04	-10000	0	-0.41	3	3
mol:PHOSPHOCHOLINE	-0.002	0.037	0.14	19	-10000	0	19
NF kappa B1/RelA/I kappa B alpha	0.044	0.029	-10000	0	-10000	0	0
AIFM1	0.006	0.035	0.17	14	-10000	0	14
BCL2	-0.008	0.12	-10000	0	-0.58	14	14

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.034	0	-9999	-10000	0	0
SNTA1	0.016	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.007	0.09	-9999	-0.29	30	30
MAPK12	0.025	0.053	-9999	-0.3	4	4
CCND1	0.01	0.071	-9999	-0.45	7	7
p38 gamma/SNTA1	0.032	0.05	-9999	-0.28	4	4
MAP2K3	0.016	0	-9999	-10000	0	0
PKN1	0.014	0.031	-9999	-0.58	1	1
G2/M transition checkpoint	0.025	0.053	-9999	-0.3	4	4
MAP2K6	0.021	0.048	-9999	-0.32	7	7
MAPT	0.004	0.1	-9999	-0.32	30	30
MAPK13	0.026	0	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.018	0.027	-9999	-0.35	2	2

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.016	0	-10000	0	-10000	0	0
HDAC3	0.016	0	-10000	0	-10000	0	0
VDR	0.012	0.042	-10000	0	-0.54	2	2
Cbp/p300/PCAF	0.032	0	-10000	0	-10000	0	0
EP300	0.016	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.035	0.058	-10000	0	-0.26	2	2
KAT2B	0.016	0	-10000	0	-10000	0	0
MAPK14	0.016	0	-10000	0	-10000	0	0
AKT1	0.017	0.083	0.22	15	-0.26	22	37
RAR alpha/9cRA/Cyclin H	-0.006	0.032	-10000	0	-10000	0	0
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.03	0.067	-10000	0	-0.29	2	2
CDC2	0.001	0	-10000	0	-10000	0	0
response to UV	0.001	0	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.018	0.052	-10000	0	-0.47	3	3
NCOR2	0.016	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.009	0.03	-10000	0	-0.4	2	2
RXRs/RARs/NRIP1/9cRA	0.016	0.093	-10000	0	-0.44	4	4
NCOA2	-0.023	0.14	-10000	0	-0.58	23	23
NCOA3	0.016	0	-10000	0	-10000	0	0
NCOA1	0.016	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.012	0.042	-10000	0	-0.54	2	2
RARG	0.017	0	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.022	0	-10000	0	-10000	0	0
MAPK3	0.016	0	-10000	0	-10000	0	0
MAPK1	0.016	0	-10000	0	-10000	0	0
MAPK8	0.012	0.054	-10000	0	-0.57	3	3
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.002	0.068	-10000	0	-0.41	4	4
RARA	0.024	0.042	-10000	0	-0.25	6	6
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.014	0.097	-10000	0	-0.46	5	5
PRKCA	0.015	0.054	-10000	0	-0.57	3	3
RXRs/RARs/NRIP1/9cRA/HDAC1	0.003	0.096	-10000	0	-0.47	4	4
RXRG	-0.08	0.16	-10000	0	-0.34	98	98
RXRA	0.032	0.042	-10000	0	-0.25	4	4
RXRB	0.021	0.048	-10000	0	-0.34	3	3
VDR/Vit D3/DNA	0.009	0.03	-10000	0	-0.4	2	2
RBP1	-0.019	0.14	-10000	0	-0.57	21	21
CRBP1/9-cic-RA	-0.014	0.1	-10000	0	-0.42	21	21
RARB	-0.026	0.16	-10000	0	-0.58	27	27
PRKCG	-0.004	0.089	-10000	0	-0.5	11	11
MNAT1	0.016	0	-10000	0	-10000	0	0
RAR alpha/RXRs	0.016	0.095	-10000	0	-0.44	4	4
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.021	0.086	-10000	0	-0.4	4	4
proteasomal ubiquitin-dependent protein catabolic process	0.036	0.063	-10000	0	-0.34	2	2
RXRs/RARs/NRIP1/9cRA/HDAC3	0.003	0.096	-10000	0	-0.47	4	4
positive regulation of DNA binding	-0.005	0.03	-10000	0	-10000	0	0
NRIP1	0.005	0.09	-10000	0	-0.65	1	1
RXRs/RARs	-0.005	0.097	-10000	0	-0.4	8	8
RXRs/RXRs/DNA/9cRA	-0.016	0.062	-10000	0	-0.44	3	3
PRKACA	0.016	0	-10000	0	-10000	0	0
CDK7	0.016	0	-10000	0	-10000	0	0
TFIIH	0.032	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.003	0.018	-10000	0	-10000	0	0
CCNH	0.016	0	-10000	0	-10000	0	0
CREBBP	0.016	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	0	0	-10000	0	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.016	0	-9999	-10000	0	0
Caspase 8 (4 units)	-0.016	0.058	-9999	-0.36	2	2
NEF	-0.009	0.051	-9999	-10000	0	0
NFKBIA	0.012	0.027	-9999	-10000	0	0
BIRC3	0.01	0.16	-9999	-0.57	24	24
CYCS	0.033	0.081	-9999	-0.37	2	2
RIPK1	0.016	0	-9999	-10000	0	0
CD247	-0.004	0.093	-9999	-0.57	7	7
MAP2K7	0.039	0.064	-9999	-0.31	1	1
protein ubiquitination	0.067	0.043	-9999	-10000	0	0
CRADD	0.016	0	-9999	-10000	0	0
DAXX	0.016	0	-9999	-10000	0	0
FAS	0.007	0.07	-9999	-0.58	5	5
BID	0.025	0.085	-9999	-0.4	2	2
NF-kappa-B/RelA/I kappa B alpha	-0.018	0.067	-9999	-10000	0	0
TRADD	0.016	0	-9999	-10000	0	0
MAP3K5	0.016	0	-9999	-10000	0	0
CFLAR	0.016	0	-9999	-10000	0	0
FADD	0.007	0.067	-9999	-0.51	6	6
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.018	0.067	-9999	-10000	0	0
MAPK8	0.044	0.066	-9999	-0.28	1	1
APAF1	0.016	0	-9999	-10000	0	0
TRAF1	0.012	0.042	-9999	-0.54	2	2
TRAF2	0.016	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.018	0.088	-9999	-0.28	22	22
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.057	0.049	-9999	-10000	0	0
CHUK	0.068	0.045	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.037	0.052	-9999	-0.28	5	5
TCRz/NEF	-0.03	0.096	-9999	-0.32	35	35
TNF	-0.009	0.11	-9999	-0.51	17	17
FASLG	-0.025	0.18	-9999	-0.56	34	34
NFKB1	0.012	0.027	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	0.016	0.069	-9999	-0.29	17	17
CASP6	-0.01	0.037	-9999	-10000	0	0
CASP7	0.047	0.15	-9999	-0.52	21	21
RELA	0.012	0.027	-9999	-10000	0	0
CASP2	0.016	0	-9999	-10000	0	0
CASP3	0.047	0.15	-9999	-0.52	21	21
TNFRSF1A	0.016	0	-9999	-10000	0	0
TNFR1A/BAG4	0.023	0	-9999	-10000	0	0
CASP8	0.016	0	-9999	-10000	0	0
CASP9	0.016	0	-9999	-10000	0	0
MAP3K14	0.063	0.047	-9999	-10000	0	0
APAF-1/Caspase 9	-0.032	0.096	-9999	-0.38	21	21
BCL2	0.039	0.084	-9999	-0.34	2	2

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.069	0.21	-10000	0	-0.58	51	51
HRAS	0.016	0	-10000	0	-10000	0	0
EGFR	-0.008	0.11	-10000	0	-0.54	15	15
AKT	0.032	0.06	-10000	0	-0.28	11	11
FOXO3	0.016	0	-10000	0	-10000	0	0
AKT1	0.016	0	-10000	0	-10000	0	0
FOXO1	0.016	0	-10000	0	-10000	0	0
AKT3	-0.003	0.1	-10000	0	-0.58	11	11
FOXO4	0.014	0.028	-10000	0	-0.51	1	1
MET	0.014	0.028	-10000	0	-0.51	1	1
PIK3CA	0.016	0	-10000	0	-10000	0	0
PIK3CB	0.016	0	-10000	0	-10000	0	0
NRAS	0.016	0	-10000	0	-10000	0	0
PIK3CG	-0.006	0.11	-10000	0	-0.56	13	13
PIK3R3	0.016	0	-10000	0	-10000	0	0
PIK3R2	0.016	0	-10000	0	-10000	0	0
NF1	0.016	0	-10000	0	-10000	0	0
RAS	-0.001	0.069	-10000	0	-0.26	6	6
ERBB2	-0.003	0.098	-10000	0	-0.51	13	13
proliferation/survival/translation	-0.036	0.027	0.19	1	-10000	0	1
PI3K	0.01	0.069	-10000	0	-0.22	10	10
PIK3R1	0.016	0	-10000	0	-10000	0	0
KRAS	0.014	0.028	-10000	0	-0.51	1	1
FOXO	0.048	0.028	-10000	0	-10000	0	0
AKT2	0.016	0	-10000	0	-10000	0	0
PTEN	0.016	0	-10000	0	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.016	0	-9999	-10000	0	0
PLK4	0.005	0.072	-9999	-0.51	7	7
regulation of centriole replication	0.019	0.053	-9999	-0.36	7	7

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.03	0.095	-9999	-0.45	13	13
KLHL20	-0.013	0.04	-9999	-0.21	3	3
CYFIP2	-0.001	0.098	-9999	-0.58	10	10
Rac1/GDP	0.058	0.061	-9999	-10000	0	0
ENAH	0.031	0.094	-9999	-0.45	13	13
AP1M1	0.016	0	-9999	-10000	0	0
RAP1B	0.016	0	-9999	-10000	0	0
RAP1A	0.016	0	-9999	-10000	0	0
CTNNB1	0.016	0	-9999	-10000	0	0
CDC42/GTP	-0.006	0.033	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.011	0.03	-9999	-0.2	1	1
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.024	0.077	-9999	-0.32	16	16
RAPGEF1	0.046	0.083	-9999	-0.38	13	13
CTNND1	0.016	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.02	0.096	-9999	-0.47	13	13
CRK	0.039	0.089	-9999	-0.42	13	13
E-cadherin/gamma catenin/alpha catenin	0.015	0.079	-9999	-0.37	14	14
alphaE/beta7 Integrin	0.018	0.046	-9999	-0.41	4	4
IQGAP1	0.016	0	-9999	-10000	0	0
NCKAP1	0.016	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.03	0.001	-9999	-10000	0	0
DLG1	0.031	0.094	-9999	-0.45	13	13
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.005	0.024	-9999	-10000	0	0
MLLT4	0.016	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.027	0.03	-9999	-0.3	3	3
PI3K	-0.006	0.03	-9999	-10000	0	0
ARF6	0.016	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	0.005	0.091	-9999	-0.44	14	14
TIAM1	0.012	0.044	-9999	-0.58	2	2
E-cadherin(dimer)/Ca2+	0.024	0.061	-9999	-0.29	13	13
AKT1	-0.003	0.017	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
CDH1	-0.006	0.11	-9999	-0.58	13	13
RhoA/GDP	0.057	0.061	-9999	-10000	0	0
actin cytoskeleton organization	0.04	0.046	-9999	-0.15	3	3
CDC42/GDP	0.057	0.061	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.017	0.061	-9999	-0.28	14	14
ITGB7	0.009	0.062	-9999	-0.58	4	4
RAC1	0.016	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.026	0.065	-9999	-0.3	13	13
E-cadherin/Ca2+/beta catenin/alpha catenin	0.015	0.06	-9999	-0.29	13	13
mol:GDP	0.053	0.069	-9999	-0.3	12	12
CDC42/GTP/IQGAP1	0.021	0	-9999	-10000	0	0
JUP	0.012	0.044	-9999	-0.58	2	2
p120 catenin/RhoA/GDP	-0.01	0.048	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0.021	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0.023	0	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0
CTNNA1	0.016	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.026	0.056	-9999	-0.2	18	18
NME1	0.014	0.028	-9999	-0.51	1	1
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.031	0.094	-9999	-0.45	13	13
regulation of cell-cell adhesion	-0.006	0.03	-9999	-10000	0	0
WASF2	-0.006	0.015	-9999	-10000	0	0
Rap1/GTP	-0.007	0.039	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.029	0.079	-9999	-0.58	2	2
CCND1	0.03	0.068	-9999	-0.24	18	18
VAV2	0.039	0.1	-9999	-0.44	15	15
RAP1/GDP	0.054	0.054	-9999	-10000	0	0
adherens junction assembly	0.031	0.091	-9999	-0.44	13	13
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.016	0	-9999	-10000	0	0
PIP5K1C	0.016	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.037	0.077	-9999	-0.55	2	2
E-cadherin/beta catenin	-0.014	0.071	-9999	-0.38	13	13
mol:GTP	0	0	-9999	-10000	0	0
SRC	0.029	0.094	-9999	-0.45	13	13
PIK3CA	0.016	0	-9999	-10000	0	0
Rac1/GTP	-0.02	0.064	-9999	-0.34	3	3
E-cadherin/beta catenin/alpha catenin	0.017	0.07	-9999	-0.34	13	13
ITGAE	0.016	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.018	0.091	-9999	-0.48	13	13

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.034	0.044	-10000	0	-0.3	6	6
HDAC3	0.016	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-10000	0	-10000	0	0
GATA1/HDAC4	0.02	0.005	-10000	0	-10000	0	0
GATA1/HDAC5	0.02	0.005	-10000	0	-10000	0	0
GATA2/HDAC5	0.006	0.08	-10000	0	-0.38	15	15
HDAC5/BCL6/BCoR	0.032	0	-10000	0	-10000	0	0
HDAC9	-0.026	0.15	-10000	0	-0.58	25	25
Glucocorticoid receptor/Hsp90/HDAC6	0.022	0.059	-10000	0	-0.34	9	9
HDAC4/ANKRA2	0.023	0	-10000	0	-10000	0	0
HDAC5/YWHAB	0.023	0	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.025	0	-10000	0	-10000	0	0
GATA2	-0.007	0.11	-10000	0	-0.53	15	15
HDAC4/RFXANK	0.022	0.02	-10000	0	-0.36	1	1
BCOR	0.016	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.016	0	-10000	0	-10000	0	0
HDAC5	0.016	0	-10000	0	-10000	0	0
GNB1/GNG2	0.016	0.056	-10000	0	-0.41	6	6
Histones	0.027	0.067	-10000	0	-10000	0	0
ADRBK1	0.016	0	-10000	0	-10000	0	0
HDAC4	0.016	0	-10000	0	-10000	0	0
XPO1	0.016	0	-10000	0	-10000	0	0
HDAC5/ANKRA2	0.023	0	-10000	0	-10000	0	0
HDAC4/Ubc9	0.023	0	-10000	0	-10000	0	0
HDAC7	0.016	0	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.022	0.023	-10000	0	-0.41	1	1
TUBA1B	0.016	0	-10000	0	-10000	0	0
HDAC6	0.016	0	-10000	0	-10000	0	0
HDAC5/RFXANK	0.022	0.02	-10000	0	-0.36	1	1
CAMK4	-0.003	0.1	-10000	0	-0.57	11	11
Tubulin/HDAC6	0.03	0.028	-10000	0	-0.34	2	2
SUMO1	0.016	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.016	0	-10000	0	-10000	0	0
GATA1	0.011	0.007	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.014	0.031	-10000	0	-0.58	1	1
NR3C1	0.001	0.093	-10000	0	-0.58	9	9
SUMO1/HDAC4	0.036	0	-10000	0	-10000	0	0
SRF	0.016	0	-10000	0	-10000	0	0
HDAC4/YWHAB	0.023	0	-10000	0	-10000	0	0
Tubulin	0.021	0.033	-10000	0	-0.41	2	2
HDAC4/14-3-3 E	0.022	0.023	-10000	0	-0.41	1	1
GNB1	0.016	0	-10000	0	-10000	0	0
RANGAP1	0.016	0	-10000	0	-10000	0	0
BCL6/BCoR	0.023	0	-10000	0	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0.032	0	-10000	0	-10000	0	0
HDAC4/SRF	0.02	0.064	-10000	0	-0.34	11	11
HDAC4/ER alpha	-0.051	0.16	-10000	0	-0.41	61	61
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.027	0.066	-10000	0	-10000	0	0
cell motility	0.029	0.028	-10000	0	-0.34	2	2
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.016	0	-10000	0	-10000	0	0
HDAC7/HDAC3	0.023	0	-10000	0	-10000	0	0
BCL6	0.016	0	-10000	0	-10000	0	0
HDAC4/CaMK II delta B	0.016	0	-10000	0	-10000	0	0
Hsp90/HDAC6	0.023	0	-10000	0	-10000	0	0
ESR1	-0.086	0.22	-10000	0	-0.58	61	61
HDAC6/HDAC11	0.018	0.045	-10000	0	-0.4	4	4
Ran/GTP/Exportin 1	0.039	0	-10000	0	-10000	0	0
NPC	0.009	0	-10000	0	-10000	0	0
MEF2C	-0.003	0.1	-10000	0	-0.58	11	11
RAN	0.016	0	-10000	0	-10000	0	0
HDAC4/MEF2C	0.036	0.056	-10000	0	-10000	0	0
GNG2	0.006	0.076	-10000	0	-0.58	6	6
NCOR2	0.016	0	-10000	0	-10000	0	0
TUBB2A	0.012	0.044	-10000	0	-0.58	2	2
HDAC11	0.009	0.061	-10000	0	-0.56	4	4
HSP90AA1	0.016	0	-10000	0	-10000	0	0
RANBP2	0.016	0	-10000	0	-10000	0	0
ANKRA2	0.016	0	-10000	0	-10000	0	0
RFXANK	0.014	0.028	-10000	0	-0.51	1	1
nuclear import	-0.033	0.018	0.31	1	-10000	0	1

×

HIF-2-alpha transcription factor network

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
MMP14	0.009	0.024	-10000	0	-10000	0	0
oxygen homeostasis	0.01	0.017	-10000	0	-10000	0	0
TCEB2	0.014	0.028	-10000	0	-0.51	1	1
TCEB1	0.016	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	0.002	0.038	-10000	0	-10000	0	0
EPO	0.12	0.21	-10000	0	-0.58	3	3
FIH (dimer)	0.026	0.015	-10000	0	-10000	0	0
APEX1	0.025	0.017	-10000	0	-10000	0	0
SERPINE1	0.13	0.22	-10000	0	-0.7	6	6
FLT1	0.012	0.024	-10000	0	-10000	0	0
ADORA2A	0.13	0.2	-10000	0	-0.55	5	5
germ cell development	0.095	0.25	-10000	0	-0.52	21	21
SLC11A2	0.14	0.2	-10000	0	-0.56	5	5
BHLHE40	0.14	0.2	-10000	0	-0.62	6	6
HIF1AN	0.026	0.015	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	0.081	0.13	-10000	0	-10000	0	0
ETS1	0.034	0.002	-10000	0	-10000	0	0
CITED2	0.009	0.019	-10000	0	-10000	0	0
KDR	0.009	0.072	-10000	0	-1.3	1	1
PGK1	0.14	0.2	-10000	0	-0.56	5	5
SIRT1	0.015	0.002	-10000	0	-10000	0	0
response to hypoxia	-0.001	0.004	-10000	0	-10000	0	0
HIF2A/ARNT	0.16	0.22	-10000	0	-0.65	5	5
EPAS1	0.089	0.1	-10000	0	-0.29	2	2
SP1	0.025	0.003	-10000	0	-10000	0	0
ABCG2	0.13	0.22	-10000	0	-0.64	4	4
EFNA1	0.13	0.21	-10000	0	-0.6	5	5
FXN	0.13	0.19	-10000	0	-0.55	5	5
POU5F1	0.095	0.26	-10000	0	-0.54	21	21
neuron apoptosis	-0.16	0.22	0.63	5	-10000	0	5
EP300	0.016	0	-10000	0	-10000	0	0
EGLN3	0.014	0.083	-10000	0	-0.56	7	7
EGLN2	0.026	0.016	-10000	0	-10000	0	0
EGLN1	0.026	0.015	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.031	0.017	-10000	0	-0.29	1	1
VHL	0.016	0	-10000	0	-10000	0	0
ARNT	0.025	0.017	-10000	0	-10000	0	0
SLC2A1	0.13	0.2	-10000	0	-0.54	6	6
TWIST1	0.069	0.3	-10000	0	-0.65	28	28
ELK1	0.025	0	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.006	0.059	-10000	0	-10000	0	0
VEGFA	0.14	0.2	-10000	0	-0.56	5	5
CREBBP	0.016	0	-10000	0	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.013	0.039	-10000	0	-0.51	2	2
Rac1/GDP	0.002	0.01	-10000	0	-10000	0	0
DOCK1	0.014	0.031	-10000	0	-0.58	1	1
ITGA4	-0.004	0.11	-10000	0	-0.57	12	12
RAC1	0.016	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	0.004	0.09	-10000	0	-0.41	16	16
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.016	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.019	0.067	-10000	0	-0.34	12	12
alpha4/beta7 Integrin/Paxillin	0.024	0.07	-10000	0	-0.3	16	16
lamellipodium assembly	0.001	0.019	-10000	0	-10000	0	0
PIK3CA	0.016	0	-10000	0	-10000	0	0
PI3K	0.023	0	-10000	0	-10000	0	0
ARF6	0.016	0	-10000	0	-10000	0	0
TLN1	0.016	0	-10000	0	-10000	0	0
PXN	0.026	0	-10000	0	-10000	0	0
PIK3R1	0.016	0	-10000	0	-10000	0	0
ARF6/GTP	-0.008	0.044	-10000	0	-10000	0	0
cell adhesion	0.035	0.057	-10000	0	-10000	0	0
CRKL/CBL	0.021	0.028	-10000	0	-0.36	2	2
alpha4/beta1 Integrin/Paxillin	0.028	0.061	-10000	0	-0.3	11	11
ITGB1	0.016	0	-10000	0	-10000	0	0
ITGB7	0.009	0.062	-10000	0	-0.58	4	4
ARF6/GDP	0.002	0.01	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.021	0.1	-10000	0	-0.58	6	6
p130Cas/Crk/Dock1	0.031	0.02	-10000	0	-0.34	1	1
VCAM1	-0.014	0.13	-10000	0	-0.57	18	18
alpha4/beta1 Integrin/Paxillin/Talin	0.036	0.058	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.036	0.058	-10000	0	-0.28	11	11
BCAR1	0.016	0	-10000	0	-10000	0	0
mol:GDP	-0.035	0.057	0.28	11	-10000	0	11
CBL	0.016	0	-10000	0	-10000	0	0
PRKACA	0.016	0	-10000	0	-10000	0	0
GIT1	0.016	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.036	0.058	-10000	0	-10000	0	0
Rac1/GTP	0.001	0.02	-10000	0	-10000	0	0

×

Class I PI3K signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	0	0.009	-9999	-10000	0	0
DAPP1	0.018	0.093	-9999	-0.43	6	6
Src family/SYK family/BLNK-LAT/BTK-ITK	0.012	0.15	-9999	-0.48	20	20
mol:DAG	0.033	0.085	-9999	-0.23	15	15
HRAS	0.017	0.001	-9999	-10000	0	0
RAP1A	0.016	0.001	-9999	-10000	0	0
ARF5/GDP	0.041	0.046	-9999	-10000	0	0
PLCG2	0.01	0.057	-9999	-0.52	4	4
PLCG1	0.016	0	-9999	-10000	0	0
ARF5	0.016	0	-9999	-10000	0	0
mol:GTP	-0.001	0.01	-9999	-10000	0	0
ARF1/GTP	0	0.009	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
YES1	0.016	0	-9999	-10000	0	0
RAP1A/GTP	-0.001	0.01	-9999	-10000	0	0
ADAP1	-0.003	0.029	-9999	-10000	0	0
ARAP3	-0.001	0.01	-9999	-10000	0	0
INPPL1	0.016	0	-9999	-10000	0	0
PREX1	0.016	0	-9999	-10000	0	0
ARHGEF6	0.011	0.054	-9999	-0.58	3	3
ARHGEF7	0.016	0	-9999	-10000	0	0
ARF1	0.016	0	-9999	-10000	0	0
NRAS	0.017	0.001	-9999	-10000	0	0
FYN	0.011	0.054	-9999	-0.58	3	3
ARF6	0.016	0	-9999	-10000	0	0
FGR	0.014	0.031	-9999	-0.58	1	1
mol:Ca2+	0.029	0.049	-9999	-10000	0	0
mol:IP4	0	0	-9999	-10000	0	0
TIAM1	0.012	0.044	-9999	-0.58	2	2
ZAP70	-0.008	0.12	-9999	-0.58	14	14
mol:IP3	0.034	0.065	-9999	-0.21	1	1
LYN	0.016	0	-9999	-10000	0	0
ARF1/GDP	0.041	0.046	-9999	-10000	0	0
RhoA/GDP	-0.002	0.01	-9999	-10000	0	0
PDK1/Src/Hsp90	0.032	0	-9999	-10000	0	0
BLNK	-0.001	0.098	-9999	-0.58	10	10
actin cytoskeleton reorganization	0.064	0.042	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
PLEKHA2	0.027	0.052	-9999	-0.34	7	7
RAC1	0.016	0	-9999	-10000	0	0
PTEN	0	0.002	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
ARF6/GTP	0	0.009	-9999	-10000	0	0
RhoA/GTP	-0.001	0.01	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT	0.014	0.12	-9999	-0.43	12	12
BLK	-0.054	0.18	-9999	-0.56	42	42
PDPK1	0.016	0	-9999	-10000	0	0
CYTH1	-0.001	0.01	-9999	-10000	0	0
HCK	-0.012	0.12	-9999	-0.56	17	17
CYTH3	-0.001	0.01	-9999	-10000	0	0
CYTH2	-0.001	0.01	-9999	-10000	0	0
KRAS	0.015	0.027	-9999	-0.5	1	1
GO:0030676	0	0	-9999	-10000	0	0
FOXO3	0.033	0.093	-9999	-0.44	13	13
SGK1	-0.018	0.091	-9999	-0.49	13	13
INPP5D	0.004	0.082	-9999	-0.58	7	7
mol:GDP	0.033	0.048	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
SYK	0.012	0.044	-9999	-0.58	2	2
ARF6/GDP	-0.002	0.01	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.01	-9999	-10000	0	0
ARAP3/RAP1A/GTP	-0.001	0.01	-9999	-10000	0	0
VAV1	-0.014	0.13	-9999	-0.57	18	18
mol:PI-3-4-P2	0.018	0.061	-9999	-0.41	7	7
RAS family/GTP/PI3K Class I	0.036	0.013	-9999	-10000	0	0
PLEKHA1	0.027	0.052	-9999	-0.34	7	7
Rac1/GDP	0.041	0.046	-9999	-10000	0	0
LAT	0.014	0.028	-9999	-0.51	1	1
Rac1/GTP	0.034	0.059	-9999	-0.27	5	5
ITK	-0.032	0.085	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.034	0.11	-9999	-0.32	16	16
LCK	0.006	0.073	-9999	-0.55	6	6
BTK	-0.016	0.062	-9999	-10000	0	0

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.051	0.038	-10000	0	-0.37	1	1
adherens junction organization	0.037	0.067	-10000	0	-0.27	14	14
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.047	0.064	-10000	0	-0.36	2	2
FMN1	0.029	0.079	-10000	0	-0.53	2	2
mol:IP3	0.042	0.038	-10000	0	-0.39	1	1
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.032	0.064	-10000	0	-0.27	14	14
CTNNB1	0.016	0.002	-10000	0	-10000	0	0
AKT1	0.048	0.044	-10000	0	-0.42	1	1
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.033	0.088	-10000	0	-0.41	13	13
CTNND1	0.017	0.001	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.039	0.061	-10000	0	-0.56	1	1
VASP	0.039	0.062	-10000	0	-0.58	1	1
ZYX	0.038	0.064	-10000	0	-0.42	2	2
JUB	0.037	0.068	-10000	0	-0.53	2	2
EGFR(dimer)	0.028	0.085	-10000	0	-0.33	8	8
E-cadherin/beta catenin-gamma catenin	-0.014	0.069	-10000	0	-0.35	14	14
mol:PI-3-4-5-P3	0.04	0.045	-10000	0	-0.45	1	1
PIK3CA	0.017	0.001	-10000	0	-10000	0	0
PI3K	0.041	0.046	-10000	0	-0.46	1	1
FYN	0.047	0.055	-10000	0	-0.3	4	4
mol:Ca2+	0.041	0.038	-10000	0	-0.38	1	1
JUP	0.012	0.044	-10000	0	-0.57	2	2
PIK3R1	0.017	0.001	-10000	0	-10000	0	0
mol:DAG	0.042	0.038	-10000	0	-0.39	1	1
CDH1	-0.006	0.11	-10000	0	-0.57	13	13
RhoA/GDP	0.047	0.064	-10000	0	-0.36	2	2
establishment of polarity of embryonic epithelium	0.039	0.061	-10000	0	-0.56	1	1
SRC	0.016	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
RHOA	0.016	0	-10000	0	-10000	0	0
EGFR	-0.008	0.11	-10000	0	-0.54	15	15
CASR	0.04	0.053	-10000	0	-0.35	1	1
RhoA/GTP	-0.005	0.026	-10000	0	-0.34	1	1
AKT2	0.048	0.044	-10000	0	-0.42	1	1
actin cable formation	0.037	0.077	-10000	0	-0.51	2	2
apoptosis	-0.046	0.042	0.41	1	-10000	0	1
CTNNA1	0.017	0.001	-10000	0	-10000	0	0
mol:GDP	0.039	0.068	-10000	0	-0.39	2	2
PIP5K1A	0.039	0.062	-10000	0	-0.58	1	1
PLCG1	0.042	0.039	-10000	0	-0.4	1	1
Rac1/GTP	-0.018	0.064	-10000	0	-0.5	2	2
homophilic cell adhesion	0.001	0.001	-10000	0	-10000	0	0

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.016	0	-9999	-10000	0	0
TRAF2/ASK1	0.021	0	-9999	-10000	0	0
ATM	0.016	0	-9999	-10000	0	0
MAP2K3	0.041	0.021	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.047	0.033	-9999	-0.22	2	2
hyperosmotic response	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
GADD45G	0.006	0.076	-9999	-0.58	6	6
TXN	0.009	0.015	-9999	-0.19	2	2
CALM1	0.016	0	-9999	-10000	0	0
GADD45A	0.016	0	-9999	-10000	0	0
GADD45B	-0.001	0.098	-9999	-0.58	10	10
MAP3K1	0.016	0	-9999	-10000	0	0
MAP3K6	0.016	0	-9999	-10000	0	0
MAP3K7	0.016	0	-9999	-10000	0	0
MAP3K4	0.016	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
ASK1/ASK2	0.023	0	-9999	-10000	0	0
TAK1/TAB family	0	0	-9999	-10000	0	0
RAC1/OSM/MEKK3	0.029	0.016	-9999	-0.26	1	1
TRAF2	0.016	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0	0.009	-9999	-10000	0	0
TRAF6	0.01	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
CAMK2B	-0.044	0.16	-9999	-0.51	40	40
CCM2	0.014	0.028	-9999	-0.51	1	1
CaM/Ca2+/CAMKIIB	-0.015	0.1	-9999	-0.3	40	40
MAPK11	0.016	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.003	0.093	-9999	-0.26	40	40
OSM/MEKK3	0.022	0.02	-9999	-0.36	1	1
TAOK1	0.019	0.019	-9999	-0.35	1	1
TAOK2	0.02	0	-9999	-10000	0	0
TAOK3	0.02	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.016	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
MAP3K5	0.016	0	-9999	-10000	0	0
MAP3K10	0.014	0.028	-9999	-0.51	1	1
MAP3K3	0.016	0	-9999	-10000	0	0
TRX/ASK1	0.018	0.013	-9999	-10000	0	0
GADD45/MTK1/MTK1	0.023	0.071	-9999	-0.31	15	15

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.019	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.092	0.028	-9999	-10000	0	0
ERC1	0.016	0	-9999	-10000	0	0
RIP2/NOD2	-0.004	0.097	-9999	-0.36	25	25
NFKBIA	0.053	0	-9999	-10000	0	0
BIRC2	0.013	0.039	-9999	-0.51	2	2
IKBKB	0.016	0	-9999	-10000	0	0
RIPK2	0.016	0	-9999	-10000	0	0
IKBKG	-0.005	0.019	-9999	-10000	0	0
IKK complex/A20	-0.012	0.045	-9999	-10000	0	0
NEMO/A20/RIP2	0.016	0	-9999	-10000	0	0
XPO1	0.016	0	-9999	-10000	0	0
NEMO/ATM	0.051	0.031	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.016	0	-9999	-10000	0	0
Exportin 1/RanGTP	0.021	0	-9999	-10000	0	0
IKK complex/ELKS	-0.003	0.011	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0.032	0	-9999	-10000	0	0
NOD2	-0.021	0.13	-9999	-0.51	25	25
NFKB1	0.019	0	-9999	-10000	0	0
RELA	0.019	0	-9999	-10000	0	0
MALT1	0.016	0	-9999	-10000	0	0
cIAP1/UbcH5C	0.021	0.028	-9999	-0.36	2	2
ATM	0.016	0	-9999	-10000	0	0
TNF/TNFR1A	0.005	0.081	-9999	-0.36	17	17
TRAF6	0.016	0	-9999	-10000	0	0
PRKCA	0.011	0.054	-9999	-0.58	3	3
CHUK	0.016	0	-9999	-10000	0	0
UBE2D3	0.016	0	-9999	-10000	0	0
TNF	-0.009	0.11	-9999	-0.51	17	17
NF kappa B1 p50/RelA	0	0	-9999	-10000	0	0
BCL10	0.016	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.053	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.019	0	-9999	-10000	0	0
TNFRSF1A	0.016	0	-9999	-10000	0	0
IKK complex	0.058	0.031	-9999	-10000	0	0
CYLD	0.016	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.005	0.023	-9999	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.038	0.076	-10000	0	-10000	0	0
BAG4	0.016	0	-10000	0	-10000	0	0
BAD	0.032	0.026	-10000	0	-10000	0	0
NFKBIA	0.016	0	-10000	0	-10000	0	0
BIRC3	-0.024	0.15	-10000	0	-0.57	24	24
BAX	0.032	0.026	-10000	0	-10000	0	0
EnzymeConsortium:3.1.4.12	0.014	0.019	-10000	0	-10000	0	0
IKBKB	0.045	0.073	-10000	0	-10000	0	0
MAP2K2	0.045	0.025	-10000	0	-10000	0	0
MAP2K1	0.045	0.025	-10000	0	-10000	0	0
SMPD1	0.02	0.019	-10000	0	-10000	0	0
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.043	0.08	-10000	0	-10000	0	0
MAP2K4	0.039	0.024	-10000	0	-10000	0	0
protein ubiquitination	0.047	0.074	-10000	0	-10000	0	0
EnzymeConsortium:2.7.1.37	0.051	0.025	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.039	0.027	-10000	0	-10000	0	0
CRADD	0.016	0	-10000	0	-10000	0	0
mol:ceramide	0.024	0.027	-10000	0	-10000	0	0
I-kappa-B-alpha/RELA/p50/ubiquitin	0.021	0	-10000	0	-10000	0	0
MADD	0.016	0	-10000	0	-10000	0	0
MAP3K1	0.032	0.025	-10000	0	-10000	0	0
TRADD	0.016	0	-10000	0	-10000	0	0
RELA/p50	0.016	0	-10000	0	-10000	0	0
MAPK3	0.048	0.025	-10000	0	-10000	0	0
MAPK1	0.048	0.025	-10000	0	-10000	0	0
p50/RELA/I-kappa-B-alpha	0.023	0	-10000	0	-10000	0	0
FADD	0.035	0.082	-10000	0	-0.29	2	2
KSR1	0.033	0.025	-10000	0	-10000	0	0
MAPK8	0.043	0.034	-10000	0	-0.23	3	3
TRAF2	0.016	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	0.045	0.073	-10000	0	-10000	0	0
TNF R/SODD	0.023	0	-10000	0	-10000	0	0
TNF	-0.009	0.11	-10000	0	-0.51	17	17
CYCS	0.037	0.032	0.15	11	-10000	0	11
IKBKG	0.045	0.073	-10000	0	-10000	0	0
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.032	0.078	-10000	0	-10000	0	0
RELA	0.016	0	-10000	0	-10000	0	0
RIPK1	0.016	0	-10000	0	-10000	0	0
AIFM1	0.037	0.032	0.15	11	-10000	0	11
TNF/TNF R/SODD	0.017	0.068	-10000	0	-0.29	17	17
TNFRSF1A	0.016	0	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.031	0.021	-10000	0	-10000	0	0
NSMAF	0.039	0.073	-10000	0	-10000	0	0
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
BCL2	-0.008	0.12	-10000	0	-0.58	14	14

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.023	0.077	-9999	-10000	0	0
PLK1	-0.053	0.22	-9999	-0.59	7	7
CDKN1B	0.075	0.1	-9999	-10000	0	0
FOXO3	-0.012	0.18	-9999	-0.5	7	7
KAT2B	0.014	0.019	-9999	-10000	0	0
FOXO1/SIRT1	0.021	0.046	-9999	-10000	0	0
CAT	-0.002	0.17	-9999	-10000	0	0
CTNNB1	0.015	0	-9999	-10000	0	0
AKT1	0.016	0.02	-9999	-10000	0	0
FOXO1	0.032	0.046	-9999	-10000	0	0
MAPK10	0.012	0.095	-9999	-0.29	32	32
mol:GTP	0.003	0	-9999	-10000	0	0
FOXO4	0.094	0.066	-9999	-10000	0	0
response to oxidative stress	-0.001	0.023	-9999	-10000	0	0
FOXO3A/SIRT1	-0.054	0.12	-9999	-0.45	3	3
XPO1	0.016	0	-9999	-10000	0	0
EP300	0.016	0.005	-9999	-10000	0	0
BCL2L11	0.023	0.034	-9999	-10000	0	0
FOXO1/SKP2	0.031	0.054	-9999	-10000	0	0
mol:GDP	-0.001	0.023	-9999	-10000	0	0
RAN	0.018	0	-9999	-10000	0	0
GADD45A	0.07	0.091	-9999	-10000	0	0
YWHAQ	0.016	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.076	0.036	-9999	-10000	0	0
MST1	-0.016	0.12	-9999	-0.51	20	20
CSNK1D	0.016	0	-9999	-10000	0	0
CSNK1E	0.016	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.056	0.048	-9999	-0.34	1	1
YWHAB	0.016	0	-9999	-10000	0	0
MAPK8	0.038	0.035	-9999	-0.28	4	4
MAPK9	0.04	0.018	-9999	-0.25	1	1
YWHAG	0.016	0	-9999	-10000	0	0
YWHAE	0.014	0.031	-9999	-0.58	1	1
YWHAZ	0.016	0	-9999	-10000	0	0
SIRT1	0.013	0.017	-9999	-10000	0	0
SOD2	0.08	0.12	-9999	-10000	0	0
RBL2	0.034	0.13	-9999	-10000	0	0
RAL/GDP	0.025	0.025	-9999	-0.31	1	1
CHUK	0.014	0.019	-9999	-10000	0	0
Ran/GTP	0.017	0	-9999	-10000	0	0
CSNK1G2	0.016	0	-9999	-10000	0	0
RAL/GTP	0.035	0.023	-9999	-0.28	1	1
CSNK1G1	0.016	0	-9999	-10000	0	0
FASLG	-0.067	0.35	-9999	-1.4	21	21
SKP2	0.007	0.067	-9999	-0.51	6	6
USP7	0.017	0	-9999	-10000	0	0
IKBKB	0.014	0.019	-9999	-10000	0	0
CCNB1	-0.051	0.22	-9999	-0.6	6	6
FOXO1-3a-4/beta catenin	0.098	0.12	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.031	0.054	-9999	-10000	0	0
CSNK1A1	0.016	0	-9999	-10000	0	0
SGK1	-0.008	0.11	-9999	-0.57	13	13
CSNK1G3	0.016	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.03	0.001	-9999	-10000	0	0
ZFAND5	0.097	0.059	-9999	-10000	0	0
SFN	-0.034	0.15	-9999	-0.52	33	33
CDK2	0.015	0.01	-9999	-10000	0	0
FOXO3A/14-3-3	0.043	0.065	-9999	-0.36	2	2
CREBBP	0.015	0.01	-9999	-10000	0	0
FBXO32	-0.002	0.17	-9999	-10000	0	0
BCL6	0.034	0.13	-9999	-10000	0	0
RALB	0.017	0	-9999	-10000	0	0
RALA	0.016	0.028	-9999	-0.5	1	1
YWHAH	0.016	0	-9999	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.029	0.14	-9999	-0.42	42	42
AKT1	0.097	0.045	-9999	-0.51	1	1
PTK2B	0.025	0.12	-9999	-0.54	4	4
VEGFR2 homodimer/Frs2	0.033	0.06	-9999	-0.7	1	1
CAV1	-0.013	0.13	-9999	-0.58	17	17
CALM1	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.044	0.057	-9999	-0.65	1	1
endothelial cell proliferation	0.053	0.1	-9999	-0.59	1	1
mol:Ca2+	0.061	0.047	-9999	-0.58	1	1
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.058	0.039	-9999	-0.61	1	1
RP11-342D11.1	0.05	0.047	-9999	-0.59	1	1
CDH5	0.014	0.031	-9999	-0.58	1	1
VEGFA homodimer	0.041	0.016	-9999	-10000	0	0
SHC1	0.014	0.028	-9999	-0.51	1	1
SHC2	-0.019	0.14	-9999	-0.57	21	21
HRAS/GDP	-0.004	0.034	-9999	-0.49	1	1
SH2D2A	0.011	0.048	-9999	-0.51	3	3
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.003	0.031	-9999	-0.47	1	1
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.047	0.049	-9999	-0.65	1	1
VEGFR1 homodimer	0.016	0	-9999	-10000	0	0
SHC/GRB2/SOS1	-0.004	0.037	-9999	-0.55	1	1
GRB10	0.057	0.078	-9999	-0.59	5	5
PTPN11	0.016	0	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
PAK1	0.014	0.031	-9999	-0.58	1	1
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.003	0.046	-9999	-0.86	1	1
HRAS	0.016	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	0.03	0.086	-9999	-0.39	4	4
HIF1A	0.014	0.028	-9999	-0.51	1	1
FRS2	0.005	0.072	-9999	-0.51	7	7
oxygen and reactive oxygen species metabolic process	-0.003	0.033	-9999	-0.6	1	1
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.016	0	-9999	-10000	0	0
Nck/Pak	0.022	0.023	-9999	-0.41	1	1
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.047	0.052	-9999	-0.65	1	1
mol:GDP	-0.004	0.036	-9999	-0.53	1	1
mol:NADP	0.087	0.037	-9999	-0.4	1	1
eNOS/Hsp90	0.09	0.035	-9999	-0.38	1	1
PIK3R1	0.016	0	-9999	-10000	0	0
mol:IP3	0.061	0.047	-9999	-0.59	1	1
HIF1A/ARNT	0.022	0.02	-9999	-0.36	1	1
SHB	0.016	0	-9999	-10000	0	0
VEGFA	0.017	0.008	-9999	-10000	0	0
VEGFC	0.011	0.054	-9999	-0.58	3	3
FAK1/Vinculin	0.051	0.099	-9999	-0.6	2	2
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.019	0.12	-9999	-0.57	4	4
PTPN6	0.014	0.028	-9999	-0.51	1	1
EPAS1	0.026	0.02	-9999	-0.34	1	1
mol:L-citrulline	0.087	0.037	-9999	-0.4	1	1
ITGAV	0.014	0.031	-9999	-0.58	1	1
PIK3CA	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.052	0.055	-9999	-0.61	1	1
VEGFR2 homodimer/VEGFA homodimer	0.055	0.051	-9999	-0.64	1	1
VEGFR2/3 heterodimer	0.04	0.041	-9999	-0.7	1	1
VEGFB	0.016	0	-9999	-10000	0	0
MAPK11	0.064	0.049	-9999	-0.6	1	1
VEGFR2 homodimer	0.039	0.046	-9999	-0.8	1	1
FLT1	0.016	0	-9999	-10000	0	0
NEDD4	0.017	0.008	-9999	-10000	0	0
MAPK3	0.028	0.079	-9999	-0.44	3	3
MAPK1	0.028	0.079	-9999	-0.44	3	3
VEGFA145/NRP2	0.005	0.091	-9999	-0.41	16	16
VEGFR1/2 heterodimer	0.04	0.041	-9999	-0.7	1	1
KDR	0.039	0.046	-9999	-0.8	1	1
VEGFA165/NRP1/VEGFR2 homodimer	0.046	0.082	-9999	-0.56	2	2
SRC	0.016	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.033	0.077	-9999	-0.44	3	3
PI3K	0.086	0.049	-9999	-0.58	1	1
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.05	0.041	-9999	-0.65	1	1
FES	0.06	0.051	-9999	-0.6	1	1
GAB1	-0.004	0.036	-9999	-0.61	1	1
VEGFR2 homodimer/VEGFA homodimer/Src	0.05	0.041	-9999	-0.65	1	1
CTNNB1	0.016	0	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
ARNT	0.016	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.077	0.066	-9999	-0.38	1	1
VEGFR2 homodimer/VEGFA homodimer/Yes	0.05	0.041	-9999	-0.65	1	1
PI3K/GAB1	0.099	0.045	-9999	-0.53	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.007	0.044	-9999	-0.58	1	1
PRKACA	0.016	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.044	0.049	-9999	-0.65	1	1
HSP90AA1	0.016	0	-9999	-10000	0	0
CDC42	0.061	0.048	-9999	-0.6	1	1
actin cytoskeleton reorganization	0.047	0.049	-9999	-0.64	1	1
PTK2	0.045	0.1	-9999	-0.66	2	2
EDG1	0.05	0.047	-9999	-0.59	1	1
mol:DAG	0.061	0.047	-9999	-0.59	1	1
CaM/Ca2+	0.063	0.044	-9999	-0.54	1	1
MAP2K3	0.065	0.051	-9999	-0.56	1	1
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.059	0.079	-9999	-0.6	5	5
PLCG1	0.061	0.048	-9999	-0.6	1	1
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.058	0.039	-9999	-0.61	1	1
IQGAP1	0.016	0	-9999	-10000	0	0
YES1	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.05	0.041	-9999	-0.65	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.049	0.044	-9999	-0.65	1	1
cell migration	0.078	0.09	-9999	-0.73	1	1
mol:PI-3-4-5-P3	0.084	0.046	-9999	-0.54	1	1
FYN	0.011	0.054	-9999	-0.58	3	3
VEGFB/NRP1	0.057	0.044	-9999	-0.55	1	1
mol:NO	0.087	0.037	-9999	-0.4	1	1
PXN	0.016	0	-9999	-10000	0	0
HRAS/GTP	-0.004	0.034	-9999	-0.49	1	1
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.058	0.079	-9999	-0.6	5	5
VHL	0.016	0	-9999	-10000	0	0
ITGB3	-0.054	0.19	-9999	-0.58	42	42
NOS3	0.089	0.04	-9999	-0.45	1	1
VEGFR2 homodimer/VEGFA homodimer/Sck	0.03	0.091	-9999	-0.55	2	2
RAC1	0.016	0	-9999	-10000	0	0
PRKCA	0.064	0.053	-9999	-0.55	1	1
PRKCB	-0.023	0.15	-9999	-0.62	3	3
VCL	0.014	0.031	-9999	-0.58	1	1
VEGFA165/NRP1	0.051	0.047	-9999	-0.59	1	1
VEGFR1/2 heterodimer/VEGFA homodimer	0.05	0.041	-9999	-0.65	1	1
VEGFA165/NRP2	0.005	0.091	-9999	-0.41	16	16
MAPKKK cascade	0.081	0.069	-9999	-0.49	5	5
NRP2	-0.011	0.12	-9999	-0.58	16	16
VEGFC homodimer	0.011	0.054	-9999	-0.57	3	3
NCK1	0.016	0	-9999	-10000	0	0
ROCK1	0.016	0	-9999	-10000	0	0
FAK1/Paxillin	0.052	0.098	-9999	-0.6	2	2
MAP3K13	0.059	0.054	-9999	-0.6	1	1
PDPK1	0.089	0.042	-9999	-0.48	1	1

×

Circadian rhythm 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.052	0.038	-9999	-10000	0	0
CLOCK	0.019	0.002	-9999	-10000	0	0
TIMELESS/CRY2	0.049	0.028	-9999	-10000	0	0
DEC1/BMAL1	0.008	0.055	-9999	-0.35	8	8
ATR	0.016	0	-9999	-10000	0	0
NR1D1	0.049	0.016	-9999	-10000	0	0
ARNTL	0.019	0.002	-9999	-10000	0	0
TIMELESS	0.047	0.031	-9999	-10000	0	0
NPAS2	0.018	0.031	-9999	-0.57	1	1
CRY2	0.016	0	-9999	-10000	0	0
mol:CO	-0.016	0.007	-9999	-10000	0	0
CHEK1	0.01	0.055	-9999	-0.51	4	4
mol:HEME	0.016	0.007	-9999	-10000	0	0
PER1	-0.008	0.12	-9999	-0.58	14	14
BMAL/CLOCK/NPAS2	0.05	0.021	-9999	-0.33	1	1
BMAL1/CLOCK	0.051	0.038	-9999	-10000	0	0
S phase of mitotic cell cycle	0.052	0.038	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	0.053	0.039	-9999	-10000	0	0
mol:NADPH	0.016	0.007	-9999	-10000	0	0
PER1/TIMELESS	0.036	0.071	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	-0.009	0.076	-9999	-0.51	8	8

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	-0.13	0.082	-10000	0	-0.34	4	4
CaM/Ca2+	0.012	0	-10000	0	-10000	0	0
AKT1	0.016	0	-10000	0	-10000	0	0
AKT2	0.016	0	-10000	0	-10000	0	0
STXBP4	0.016	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	-0.13	0.11	0.22	1	-0.34	6	7
YWHAZ	0.016	0	-10000	0	-10000	0	0
CALM1	0.016	0	-10000	0	-10000	0	0
YWHAQ	0.016	0	-10000	0	-10000	0	0
TBC1D4	0.026	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.016	0	-10000	0	-10000	0	0
YWHAB	0.016	0	-10000	0	-10000	0	0
SNARE/Synip	0.032	0	-10000	0	-10000	0	0
YWHAG	0.016	0	-10000	0	-10000	0	0
ASIP	0.006	0.048	-10000	0	-0.51	3	3
PRKCI	0.016	0	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0.012	0	-10000	0	-10000	0	0
RHOQ	0.016	0	-10000	0	-10000	0	0
GYS1	0.036	0	-10000	0	-10000	0	0
PRKCZ	0.012	0.044	-10000	0	-0.58	2	2
TRIP10	0.014	0.031	-10000	0	-0.58	1	1
TC10/GTP/CIP4/Exocyst	0.02	0.02	-10000	0	-0.35	1	1
AS160/14-3-3	0.042	0.043	-10000	0	-0.3	1	1
VAMP2	0.016	0	-10000	0	-10000	0	0
SLC2A4	-0.14	0.12	0.23	1	-0.38	6	7
STX4	0.016	0	-10000	0	-10000	0	0
GSK3B	0.03	0	-10000	0	-10000	0	0
SFN	-0.034	0.15	-10000	0	-0.52	33	33
LNPEP	0.016	0	-10000	0	-10000	0	0
YWHAE	0.014	0.031	-10000	0	-0.58	1	1

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.016	0	-10000	0	-10000	0	0
mol:PIP3	-0.006	0.04	-10000	0	-0.29	7	7
FRAP1	0.017	0.008	-10000	0	-10000	0	0
AKT1	0.028	0.036	-10000	0	-10000	0	0
INSR	0.016	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.011	0	-10000	0	-10000	0	0
mol:GTP	-0.003	0.023	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.001	0.005	-10000	0	-10000	0	0
TSC2	0.015	0	-10000	0	-10000	0	0
RHEB/GDP	-0.003	0.019	-10000	0	-10000	0	0
TSC1	0.016	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.012	0.051	-10000	0	-0.35	7	7
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.001	0.007	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.016	0	-10000	0	-10000	0	0
RPS6KB1	0.03	0.019	-10000	0	-10000	0	0
MAP3K5	0.012	0	-10000	0	-10000	0	0
PIK3R1	0.016	0	-10000	0	-10000	0	0
apoptosis	0.012	0	-10000	0	-10000	0	0
mol:LY294002	0	0	-10000	0	-0.001	7	7
EIF4B	0.036	0.018	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.002	0.011	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	0	0	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.023	0.047	-10000	0	-0.31	7	7
mTOR/RHEB/GTP/Raptor/GBL	0.035	0.012	-10000	0	-10000	0	0
FKBP1A	0.016	0	-10000	0	-10000	0	0
RHEB/GTP	-0.003	0.019	-10000	0	-10000	0	0
mol:Amino Acids	0	0	-10000	0	-0.001	7	7
FKBP12/Rapamycin	0.012	0.002	-10000	0	-10000	0	0
PDPK1	-0.005	0.036	-10000	0	-0.26	7	7
EIF4E	0.016	0	-10000	0	-10000	0	0
ASK1/PP5C	0.026	0.005	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.02	0	-10000	0	-10000	0	0
TSC1/TSC2	0.042	0.031	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	0.001	7	-10000	0	7
RPS6	0.016	0	-10000	0	-10000	0	0
PPP5C	0.016	0	-10000	0	-10000	0	0
EIF4G1	0.016	0	-10000	0	-10000	0	0
IRS1	0.002	0.054	-10000	0	-0.38	7	7
INS	0	0	-10000	0	-10000	0	0
PTEN	0.015	0	-10000	0	-10000	0	0
PDK2	-0.005	0.036	-10000	0	-0.26	7	7
EIF4EBP1	0.012	0.015	-10000	0	-10000	0	0
PIK3CA	0.016	0	-10000	0	-10000	0	0
PPP2R5D	0.024	0.007	-10000	0	-10000	0	0
peptide biosynthetic process	0.02	0	-10000	0	-10000	0	0
RHEB	0.016	0	-10000	0	-10000	0	0
EIF4A1	0.016	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	-10000	0	-10000	0	0
EEF2	0.02	0	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.02	0.013	-10000	0	-10000	0	0

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.037	0.017	-9999	-10000	0	0
VEGFR1 homodimer/NRP1	0.026	0.016	-9999	-0.28	1	1
mol:DAG	0.035	0.055	-9999	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	0.034	0.015	-9999	-10000	0	0
CaM/Ca2+	0.042	0.051	-9999	-10000	0	0
HIF1A	0.024	0.027	-9999	-0.49	1	1
GAB1	0.016	0	-9999	-10000	0	0
AKT1	0.06	0.042	-9999	-10000	0	0
PLCG1	0.036	0.055	-9999	-10000	0	0
NOS3	0.065	0.042	-9999	-10000	0	0
CBL	0.016	0	-9999	-10000	0	0
mol:NO	0.065	0.041	-9999	-10000	0	0
FLT1	0.035	0.02	-9999	-0.34	1	1
PGF	-0.002	0.094	-9999	-0.51	12	12
VEGFR1 homodimer/NRP2/VEGFR121	0.029	0.072	-9999	-10000	0	0
CALM1	0.016	0	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
eNOS/Hsp90	0.071	0.04	-9999	-10000	0	0
endothelial cell proliferation	-0.022	0.13	-9999	-0.42	7	7
mol:Ca2+	0.035	0.054	-9999	-10000	0	0
MAPK3	0.046	0.055	-9999	-10000	0	0
MAPK1	0.046	0.055	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
PLGF homodimer	-0.002	0.094	-9999	-0.51	12	12
PRKACA	0.016	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.013	0.13	-9999	-0.58	17	17
VEGFA homodimer	0.016	0	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0.037	0.017	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.053	0.054	-9999	-10000	0	0
PI3K	0.043	0.052	-9999	-10000	0	0
PRKCA	0.04	0.058	-9999	-10000	0	0
PRKCB	-0.051	0.16	-9999	-0.53	4	4
VEGFR1 homodimer/PLGF homodimer	0.027	0.06	-9999	-10000	0	0
VEGFA	0.016	0	-9999	-10000	0	0
VEGFB	0.016	0	-9999	-10000	0	0
mol:IP3	0.035	0.055	-9999	-10000	0	0
RASA1	0.045	0.015	-9999	-10000	0	0
NRP2	-0.011	0.12	-9999	-0.58	16	16
VEGFR1 homodimer	0.035	0.02	-9999	-0.34	1	1
VEGFB homodimer	0.016	0	-9999	-10000	0	0
NCK1	0.016	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.058	0.074	-9999	-0.41	1	1
PTPN11	0.016	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.041	0.051	-9999	-10000	0	0
mol:L-citrulline	0.065	0.041	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.053	0.014	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.045	0.015	-9999	-10000	0	0
CD2AP	0.016	0	-9999	-10000	0	0
PI3K/GAB1	0.049	0.049	-9999	-10000	0	0
PDPK1	0.048	0.049	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.045	0.015	-9999	-10000	0	0
mol:NADP	0.065	0.041	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.051	0.014	-9999	-10000	0	0
VEGFR1 homodimer/NRP2	0.021	0.079	-9999	-0.34	16	16

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.016	0	-9999	-10000	0	0
SMAD2	0.016	0	-9999	-10000	0	0
SMAD3	0.048	0	-9999	-10000	0	0
SMAD3/SMAD4	0.055	0.005	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	0.032	0	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	0.045	0.019	-9999	-10000	0	0
PPM1A	0.016	0	-9999	-10000	0	0
CALM1	0.016	0	-9999	-10000	0	0
SMAD2/SMAD4	0.024	0	-9999	-10000	0	0
MAP3K1	0.016	0	-9999	-10000	0	0
TRAP-1/SMAD4	0.017	0.051	-9999	-0.41	5	5
MAPK3	0.016	0	-9999	-10000	0	0
MAPK1	0.016	0	-9999	-10000	0	0
NUP214	0.016	0	-9999	-10000	0	0
CTDSP1	0.016	0	-9999	-10000	0	0
CTDSP2	0.016	0	-9999	-10000	0	0
CTDSPL	0.016	0	-9999	-10000	0	0
KPNB1	0.016	0	-9999	-10000	0	0
TGFBRAP1	0.007	0.07	-9999	-0.58	5	5
UBE2I	0.016	0	-9999	-10000	0	0
NUP153	0.016	0	-9999	-10000	0	0
KPNA2	0.013	0.039	-9999	-0.51	2	2
PIAS4	0.016	0	-9999	-10000	0	0

×

Arf6 downstream 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
PLAUR	0.05	0.005	-10000	0	-10000	0	0
regulation of axonogenesis	-0.034	0.014	0.22	1	-10000	0	1
myoblast fusion	-0.023	0.013	-10000	0	-10000	0	0
mol:GTP	0	0.003	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.039	0.032	0.3	3	-10000	0	3
ARF1/GTP	0	0.001	-10000	0	-10000	0	0
mol:GM1	0.013	0.004	-10000	0	-10000	0	0
mol:Choline	0.032	0.02	-10000	0	-0.35	1	1
lamellipodium assembly	0	0.014	-10000	0	-10000	0	0
MAPK3	0.035	0.003	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.039	0.032	-10000	0	-0.31	3	3
ARF1	0.016	0	-10000	0	-10000	0	0
ARF6/GDP	0.023	0.013	-10000	0	-10000	0	0
ARF1/GDP	0.032	0.012	-10000	0	-10000	0	0
ARF6	0.015	0.002	-10000	0	-10000	0	0
RAB11A	0.016	0	-10000	0	-10000	0	0
TIAM1	0.014	0.044	-10000	0	-0.57	2	2
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.035	0.003	-10000	0	-10000	0	0
actin filament bundle formation	-0.03	0.011	-10000	0	-10000	0	0
KALRN	-0.003	0.032	-10000	0	-0.26	5	5
RAB11FIP3/RAB11A	0.023	0	-10000	0	-10000	0	0
RhoA/GDP	0.031	0.012	-10000	0	-10000	0	0
NME1	0.016	0.028	-10000	0	-0.5	1	1
Rac1/GDP	0.031	0.012	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0	0.003	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	0	0.014	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
liver development	0	0.003	-10000	0	-10000	0	0
ARF6/GTP	0	0.003	-10000	0	-10000	0	0
RhoA/GTP	0	0.001	-10000	0	-10000	0	0
mol:GDP	0	0.013	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	0	0.002	-10000	0	-10000	0	0
RHOA	0.016	0	-10000	0	-10000	0	0
PLD1	0.024	0.023	-10000	0	-0.4	1	1
RAB11FIP3	0.016	0	-10000	0	-10000	0	0
tube morphogenesis	0	0.014	-10000	0	-10000	0	0
ruffle organization	0.034	0.014	-10000	0	-0.22	1	1
regulation of epithelial cell migration	0	0.003	-10000	0	-10000	0	0
PLD2	0.025	0.004	-10000	0	-10000	0	0
PIP5K1A	0.034	0.014	-10000	0	-0.22	1	1
mol:Phosphatidic acid	0.032	0.02	-10000	0	-0.35	1	1
Rac1/GTP	0	0.015	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.008	0.037	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.048	0.034	-9999	-10000	0	0
SUMO1	0.016	0	-9999	-10000	0	0
ZFPM1	0.016	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.025	0	-9999	-10000	0	0
FKBP3	0.016	0	-9999	-10000	0	0
Histones	0.048	0.027	-9999	-10000	0	0
YY1/LSF	0.037	0	-9999	-10000	0	0
SMG5	0.016	0	-9999	-10000	0	0
RAN	0.016	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	0.031	0.039	-9999	-10000	0	0
I kappa B alpha/HDAC1	0.032	0.03	-9999	-10000	0	0
SAP18	0.016	0	-9999	-10000	0	0
RELA	0.038	0.032	-9999	-10000	0	0
HDAC1/Smad7	0.031	0.02	-9999	-0.34	1	1
RANGAP1	0.016	0	-9999	-10000	0	0
HDAC3/TR2	0.032	0.03	-9999	-10000	0	0
NuRD/MBD3 Complex	0.056	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.041	0.029	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.007	0.11	-9999	-0.53	15	15
GATA1	0.011	0.007	-9999	-10000	0	0
Mad/Max	0.022	0.02	-9999	-0.36	1	1
NuRD/MBD3 Complex/GATA1/Fog1	0.066	0.003	-9999	-10000	0	0
RBBP7	0.016	0	-9999	-10000	0	0
NPC	0.009	0	-9999	-10000	0	0
RBBP4	0.016	0	-9999	-10000	0	0
MAX	0.016	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.016	0	-9999	-10000	0	0
NFKBIA	0.026	0.034	-9999	-10000	0	0
KAT2B	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.051	0	-9999	-10000	0	0
SIN3 complex	0.04	0	-9999	-10000	0	0
SMURF1	0.016	0	-9999	-10000	0	0
CHD3	0.016	0	-9999	-10000	0	0
SAP30	0.016	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.016	0	-9999	-10000	0	0
YY1/HDAC3	0.045	0.028	-9999	-10000	0	0
YY1/HDAC2	0.037	0	-9999	-10000	0	0
YY1/HDAC1	0.037	0	-9999	-10000	0	0
NuRD/MBD2 Complex (MeCP1)	0.056	0	-9999	-10000	0	0
PPARG	0.016	0.096	-9999	-0.33	22	22
HDAC8/hEST1B	0.032	0	-9999	-10000	0	0
UBE2I	0.016	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.016	0	-9999	-10000	0	0
TNFRSF1A	0.016	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.032	0.03	-9999	-10000	0	0
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.03	0.02	-9999	-0.34	1	1
CREBBP	0.016	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.059	0	-9999	-10000	0	0
HDAC1	0.016	0	-9999	-10000	0	0
HDAC3	0.026	0.034	-9999	-10000	0	0
HDAC2	0.016	0	-9999	-10000	0	0
YY1	0.035	0	-9999	-10000	0	0
HDAC8	0.016	0	-9999	-10000	0	0
SMAD7	0.014	0.031	-9999	-0.58	1	1
NCOR2	0.016	0	-9999	-10000	0	0
MXD1	0.014	0.028	-9999	-0.51	1	1
STAT3	0.03	0	-9999	-10000	0	0
NFKB1	0.016	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.016	0	-9999	-10000	0	0
YY1/LSF/HDAC1	0.044	0	-9999	-10000	0	0
YY1/SAP30/HDAC1	0.044	0	-9999	-10000	0	0
EP300	0.016	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.03	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.026	0.034	-9999	-10000	0	0
histone deacetylation	0.055	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.042	0.028	-9999	-10000	0	0
nuclear export	-0.031	0	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
GATAD2B	0.016	0	-9999	-10000	0	0
GATAD2A	0.016	0	-9999	-10000	0	0
GATA2/HDAC3	0.019	0.067	-9999	-0.3	5	5
GATA1/HDAC1	0.02	0.005	-9999	-10000	0	0
GATA1/HDAC3	0.02	0.033	-9999	-10000	0	0
CHD4	0.016	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	0.005	0.081	-9999	-0.36	17	17
SIN3/HDAC complex/Mad/Max	0.055	0.005	-9999	-10000	0	0
NuRD Complex	0.065	0	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.003	0.016	-9999	-10000	0	0
SIN3B	0.016	0	-9999	-10000	0	0
MTA2	0.016	0	-9999	-10000	0	0
SIN3A	0.016	0	-9999	-10000	0	0
XPO1	0.016	0	-9999	-10000	0	0
SUMO1/HDAC1	0.036	0	-9999	-10000	0	0
HDAC complex	0.04	0	-9999	-10000	0	0
GATA1/Fog1	0.02	0.005	-9999	-10000	0	0
FKBP25/HDAC1/HDAC2	0.032	0	-9999	-10000	0	0
TNF	-0.009	0.11	-9999	-0.51	17	17
negative regulation of cell growth	0.055	0.005	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.056	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.039	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.042	0.036	-9999	-10000	0	0
SIN3/HDAC complex/NCoR1	0.053	0	-9999	-10000	0	0
TFCP2	0.016	0	-9999	-10000	0	0
NR2C1	0.016	0	-9999	-10000	0	0
MBD3	0.016	0	-9999	-10000	0	0
MBD2	0.016	0	-9999	-10000	0	0

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.022	0.023	-9999	-0.41	1	1
FBXW11	0.016	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.027	0.037	-9999	-0.32	4	4
NF kappa B1 p50/RelA/I kappa B alpha	0.052	0.029	-9999	-10000	0	0
NFKBIA	0.029	0.033	-9999	-10000	0	0
MAPK14	0.016	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.031	0	-9999	-10000	0	0
ARRB2	0.02	0	-9999	-10000	0	0
REL	0.009	0.059	-9999	-0.54	4	4
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.03	0.02	-9999	-0.34	1	1
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.031	0	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
NF kappa B1 p50 dimer	0.024	0	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
NFKB1	0.026	0	-9999	-10000	0	0
RELA	0.016	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.037	0.032	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.056	0.028	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
PI3K	0.023	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.037	0.033	-9999	-10000	0	0
IKBKB	0.016	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.016	0	-9999	-10000	0	0
SYK	0.012	0.044	-9999	-0.58	2	2
I kappa B alpha/PIK3R1	0.036	0.031	-9999	-10000	0	0
cell death	0.054	0.027	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	0.027	0.037	-9999	-0.32	4	4
LCK	0.006	0.073	-9999	-0.55	6	6
BCL3	0.014	0.031	-9999	-0.58	1	1

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.016	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
MDM2/SUMO1	0.027	0.048	-9999	-0.23	12	12
HDAC4	0.016	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
SUMO1	0.016	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.02	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.033	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.016	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.016	0	-9999	-10000	0	0
SUMO1/HDAC4	0.036	0	-9999	-10000	0	0
SUMO1/HDAC1	0.036	0	-9999	-10000	0	0
RANGAP1	0.016	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	0.03	0.053	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.025	0	-9999	-10000	0	0
Ran/GTP	0.032	0	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	-0.002	0.094	-9999	-0.51	12	12
UBE2I	0.016	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.039	0	-9999	-10000	0	0
NPC	0.009	0	-9999	-10000	0	0
PIAS2	0.016	0	-9999	-10000	0	0
PIAS1	0.016	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0	0	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.024	0	-9999	-10000	0	0
AP2	0.023	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0	-9999	-10000	0	0
CLTB	0.016	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.03	0	-9999	-10000	0	0
CD4	0.012	0.044	-9999	-0.58	2	2
CLTA	0.016	0	-9999	-10000	0	0
mol:GTP	0.002	0	-9999	-10000	0	0
ARFGAP1	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
ARF1/GTP	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.032	0	-9999	-10000	0	0
mol:Choline	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.016	0	-9999	-10000	0	0
DDEF1	0	0	-9999	-10000	0	0
ARF1/GDP	0	0	-9999	-10000	0	0
AP2M1	0.016	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0.02	0	-9999	-10000	0	0
Rac/GTP	0.013	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.029	0	-9999	-10000	0	0
ARFIP2	0.014	0	-9999	-10000	0	0
COPA	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.03	0	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0	-9999	-10000	0	0
GGA3	0.016	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0.022	0	-9999	-10000	0	0
AP2A1	0.016	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.032	0	-9999	-10000	0	0
ARF1/GDP/Membrin	0.022	0	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0	0	-9999	-10000	0	0
CYTH2	0.016	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0	0	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0.012	0	-9999	-10000	0	0
mol:Brefeldin A	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.04	0.018	-9999	-0.2	2	2
PLD2	0	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.013	0	-9999	-10000	0	0
PIP5K1A	0	0	-9999	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0	0	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	0.013	0	-9999	-10000	0	0
GOSR2	0	0	-9999	-10000	0	0
USO1	0	0	-9999	-10000	0	0
GBF1	0	0	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.03	0.028	-9999	-0.34	2	2

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
IKK alpha homodimer	0.023	-9999	-9999
FBXW11	0.016	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	0	-9999	-9999
beta TrCP1/SCF ubiquitin ligase complex	0.016	-9999	-9999
CHUK	0.016	-9999	-9999
NF kappa B2 p100/RelB	0.046	-9999	-9999
NFKB1	0.016	-9999	-9999
MAP3K14	0.016	-9999	-9999
NF kappa B1 p50/RelB	0.023	-9999	-9999
RELB	0.016	-9999	-9999
NFKB2	0.016	-9999	-9999
NF kappa B2 p52/RelB	0.021	-9999	-9999
regulation of B cell activation	0.021	-9999	-9999

pid_entity	TCGA.ZF.AA5P	TCGA.ZF.AA5H	TCGA.ZF.AA56	TCGA.ZF.AA54
109_MAP3K5	0.063	-0.044	0.063	-0.036
47_PPARGC1A	0.016	-0.58	0.016	0.016
105_BMP4	0.016	0.016	0.016	0.016
105_BMP6	0.016	0.016	0.016	0.016
105_BMP7	0.016	-0.58	0.016	-0.58
105_BMP2	0.016	0.016	0.016	0.016
131_RELN/VLDLR	0.04	0.04	-0.57	-0.25
30_TGFB1/TGF beta receptor Type II	0.019	0.019	0.019	0.018
84_STAT5B	0.036	0.051	0.0069	-0.013
84_STAT5A	0.036	0.051	0.0069	-0.013