PARADIGM pathway analysis of mRNASeq expression and copy number data - Brain Lower Grade Glioma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
Ephrin A reverse signaling	87
IL23-mediated signaling events	87
Signaling mediated by p38-alpha and p38-beta	67
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	62
FOXM1 transcription factor network	62
Aurora B signaling	61
Signaling events regulated by Ret tyrosine kinase	58
IL12-mediated signaling events	56
TCR signaling in naïve CD8+ T cells	56
Syndecan-1-mediated signaling events	53

Pathway.Name	Significance.Ratio	Avg.Num.Perturbations	Total.Perturbations	Num.Entities	Min.Mean.Truth	Max.Mean.Truth	Min.Mean.Within	Max.Mean.Within	Min.Mean.Any	Max.Mean.Within.1
Ephrin A reverse signaling	0.1686	87	611	7	-0.063	0	1000	-1000	-0.007	-1000
IL23-mediated signaling events	0.1686	87	5278	60	-0.49	0.026	1000	-1000	-0.073	-1000
Signaling mediated by p38-alpha and p38-beta	0.1298	67	2948	44	-0.1	0.026	1000	-1000	-0.019	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.1202	62	4227	68	-0.3	0.18	1000	-1000	-0.074	-1000
FOXM1 transcription factor network	0.1202	62	3181	51	-0.27	0.026	1000	-1000	-0.092	-1000
Aurora B signaling	0.1182	61	4090	67	-0.26	0.046	1000	-1000	-0.031	-1000
Signaling events regulated by Ret tyrosine kinase	0.1124	58	4803	82	-0.074	0.026	1000	-1000	-0.042	-1000
IL12-mediated signaling events	0.1085	56	4956	87	-0.4	0.073	1000	-1000	-0.078	-1000
TCR signaling in naïve CD8+ T cells	0.1085	56	5223	93	-0.18	0.21	1000	-1000	-0.04	-1000
Syndecan-1-mediated signaling events	0.1027	53	1819	34	-0.075	0.026	1000	-1000	-0.027	-1000
Thromboxane A2 receptor signaling	0.1008	52	5461	105	-0.13	0.034	1000	-1000	-0.032	-1000
Endothelins	0.0950	49	4725	96	-0.13	0.026	1000	-1000	-0.043	-1000
Signaling events mediated by the Hedgehog family	0.0911	47	2488	52	-0.093	0.048	1000	-1000	-0.029	-1000
Effects of Botulinum toxin	0.0911	47	1224	26	-0.088	0.026	1000	-1000	-0.001	-1000
Syndecan-4-mediated signaling events	0.0911	47	3214	67	-0.094	0.035	1000	-1000	-0.03	-1000
Reelin signaling pathway	0.0891	46	2617	56	-0.1	0.059	1000	-1000	-0.027	-1000
TCGA08_retinoblastoma	0.0891	46	371	8	-0.023	0.042	1000	-1000	-0.002	-1000
ErbB2/ErbB3 signaling events	0.0814	42	2749	65	-0.1	0.037	1000	-1000	-0.048	-1000
FOXA2 and FOXA3 transcription factor networks	0.0814	42	1933	46	-0.22	0.03	1000	-1000	-0.09	-1000
Syndecan-3-mediated signaling events	0.0795	41	1442	35	-0.061	0.063	1000	-1000	-0.018	-1000
Arf6 signaling events	0.0775	40	2490	62	-0.14	0.054	1000	-1000	-0.03	-1000
Aurora C signaling	0.0756	39	273	7	-0.072	0.011	1000	-1000	-0.015	-1000
IL4-mediated signaling events	0.0736	38	3475	91	-0.42	0.27	1000	-1000	-0.11	-1000
Visual signal transduction: Rods	0.0736	38	2025	52	-0.1	0.026	1000	-1000	-0.024	-1000
Caspase cascade in apoptosis	0.0717	37	2748	74	-0.13	0.05	1000	-1000	-0.034	-1000
HIF-1-alpha transcription factor network	0.0717	37	2839	76	-0.11	0.056	1000	-1000	-0.048	-1000
a4b1 and a4b7 Integrin signaling	0.0717	37	187	5	-0.008	0.012	1000	-1000	0.007	-1000
E-cadherin signaling events	0.0717	37	188	5	-0.046	0.026	1000	-1000	0.006	-1000
amb2 Integrin signaling	0.0698	36	2976	82	-0.15	0.028	1000	-1000	-0.024	-1000
BCR signaling pathway	0.0698	36	3648	99	-0.095	0.044	1000	-1000	-0.045	-1000
Glypican 2 network	0.0678	35	142	4	-0.002	0.004	1000	-1000	0.007	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0678	35	2646	74	-0.063	0.059	1000	-1000	-0.049	-1000
EGFR-dependent Endothelin signaling events	0.0678	35	741	21	-0.034	0.037	1000	-1000	-0.034	-1000
Ras signaling in the CD4+ TCR pathway	0.0678	35	601	17	-0.054	0.034	1000	-1000	-0.026	-1000
p75(NTR)-mediated signaling	0.0659	34	4325	125	-0.073	0.063	1000	-1000	-0.046	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0659	34	1782	52	-0.15	0.067	1000	-1000	-0.031	-1000
LPA receptor mediated events	0.0659	34	3513	102	-0.1	0.03	1000	-1000	-0.067	-1000
Osteopontin-mediated events	0.0640	33	1291	38	-0.05	0.027	1000	-1000	-0.02	-1000
Nongenotropic Androgen signaling	0.0640	33	1753	52	-0.075	0.036	1000	-1000	-0.024	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0620	32	2750	85	-0.17	0.038	1000	-1000	-0.036	-1000
PDGFR-alpha signaling pathway	0.0620	32	1408	44	-0.1	0.032	1000	-1000	-0.029	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0581	30	1634	54	-0.073	0.033	1000	-1000	-0.028	-1000
Glypican 1 network	0.0581	30	1450	48	-0.08	0.05	1000	-1000	-0.022	-1000
Fc-epsilon receptor I signaling in mast cells	0.0581	30	2951	97	-0.06	0.042	1000	-1000	-0.052	-1000
Ceramide signaling pathway	0.0581	30	2294	76	-0.068	0.045	1000	-1000	-0.028	-1000
Calcium signaling in the CD4+ TCR pathway	0.0581	30	951	31	-0.094	0.025	1000	-1000	-0.043	-1000
IL1-mediated signaling events	0.0562	29	1846	62	-0.073	0.045	1000	-1000	-0.025	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0562	29	2620	88	-0.087	0.029	1000	-1000	-0.059	-1000
BMP receptor signaling	0.0523	27	2226	81	-0.079	0.044	1000	-1000	-0.033	-1000
PLK1 signaling events	0.0523	27	2318	85	-0.078	0.038	1000	-1000	-0.031	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0523	27	999	37	-0.034	0.046	1000	-1000	-0.022	-1000
S1P5 pathway	0.0523	27	459	17	-0.053	0.026	1000	-1000	-0.01	-1000
Ephrin B reverse signaling	0.0523	27	1298	48	-0.027	0.027	1000	-1000	-0.017	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0504	26	907	34	-0.017	0.04	1000	-1000	-0.019	-1000
Visual signal transduction: Cones	0.0504	26	1010	38	-0.055	0.034	1000	-1000	-0.007	-1000
IL6-mediated signaling events	0.0504	26	1998	75	-0.1	0.04	1000	-1000	-0.04	-1000
Regulation of nuclear SMAD2/3 signaling	0.0484	25	3438	136	-0.18	0.16	1000	-1000	-0.037	-1000
Glucocorticoid receptor regulatory network	0.0484	25	2897	114	-0.27	0.14	1000	-1000	-0.065	-1000
Canonical Wnt signaling pathway	0.0484	25	1322	51	-0.13	0.066	1000	-1000	-0.041	-1000
JNK signaling in the CD4+ TCR pathway	0.0465	24	414	17	-0.025	0.026	1000	-1000	-0.025	-1000
Noncanonical Wnt signaling pathway	0.0465	24	626	26	-0.048	0.026	1000	-1000	-0.032	-1000
E-cadherin signaling in the nascent adherens junction	0.0465	24	1893	76	-0.046	0.048	1000	-1000	-0.045	-1000
Coregulation of Androgen receptor activity	0.0446	23	1753	76	-0.082	0.05	1000	-1000	-0.016	-1000
TCGA08_p53	0.0446	23	164	7	-0.017	0.025	1000	-1000	-0.011	-1000
Presenilin action in Notch and Wnt signaling	0.0426	22	1378	61	-0.13	0.063	1000	-1000	-0.036	-1000
FAS signaling pathway (CD95)	0.0426	22	1071	47	-0.099	0.039	1000	-1000	-0.038	-1000
EPHB forward signaling	0.0426	22	1890	85	-0.029	0.054	1000	-1000	-0.046	-1000
Syndecan-2-mediated signaling events	0.0407	21	1466	69	-0.061	0.038	1000	-1000	-0.029	-1000
Cellular roles of Anthrax toxin	0.0407	21	856	39	-0.13	0.029	1000	-1000	-0.017	-1000
Retinoic acid receptors-mediated signaling	0.0407	21	1257	58	-0.088	0.051	1000	-1000	-0.05	-1000
TCGA08_rtk_signaling	0.0407	21	571	26	-0.047	0.061	1000	-1000	-0.007	-1000
Rapid glucocorticoid signaling	0.0407	21	428	20	-0.075	0.027	1000	-1000	-0.004	-1000
E-cadherin signaling in keratinocytes	0.0407	21	909	43	-0.046	0.027	1000	-1000	-0.027	-1000
Signaling events mediated by HDAC Class III	0.0388	20	814	40	-0.064	0.05	1000	-1000	-0.021	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0388	20	2493	120	-0.11	0.074	1000	-1000	-0.035	-1000
IL27-mediated signaling events	0.0368	19	996	51	-0.085	0.026	1000	-1000	-0.048	-1000
S1P1 pathway	0.0349	18	680	36	-0.095	0.026	1000	-1000	-0.029	-1000
IL2 signaling events mediated by PI3K	0.0349	18	1090	58	-0.075	0.041	1000	-1000	-0.032	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0349	18	1471	78	-0.017	0.037	1000	-1000	-0.055	-1000
Signaling events mediated by PTP1B	0.0329	17	1297	76	-0.072	0.04	1000	-1000	-0.04	-1000
EPO signaling pathway	0.0329	17	973	55	-0.029	0.07	1000	-1000	-0.034	-1000
ceramide signaling pathway	0.0329	17	840	49	-0.06	0.037	1000	-1000	-0.034	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0310	16	1403	83	-0.094	0.051	1000	-1000	-0.024	-1000
IL2 signaling events mediated by STAT5	0.0310	16	363	22	-0.028	0.027	1000	-1000	-0.04	-1000
LPA4-mediated signaling events	0.0291	15	181	12	-0.031	0.005	1000	-1000	-0.019	-1000
Paxillin-dependent events mediated by a4b1	0.0291	15	556	36	-0.038	0.047	1000	-1000	-0.027	-1000
Integrins in angiogenesis	0.0291	15	1317	84	-0.024	0.057	1000	-1000	-0.037	-1000
Wnt signaling	0.0291	15	105	7	-0.007	0.01	1000	-1000	-0.013	-1000
Plasma membrane estrogen receptor signaling	0.0291	15	1351	86	-0.039	0.038	1000	-1000	-0.04	-1000
S1P4 pathway	0.0291	15	397	25	-0.053	0.045	1000	-1000	-0.02	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0271	14	661	45	-0.06	0.061	1000	-1000	-0.05	-1000
Signaling events mediated by PRL	0.0271	14	481	34	-0.059	0.033	1000	-1000	-0.029	-1000
Regulation of Androgen receptor activity	0.0271	14	1030	70	-0.066	0.036	1000	-1000	-0.047	-1000
BARD1 signaling events	0.0252	13	755	57	-0.041	0.051	1000	-1000	-0.033	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0252	13	387	28	-0.053	0.032	1000	-1000	-0.016	-1000
VEGFR1 specific signals	0.0252	13	749	56	-0.038	0.055	1000	-1000	-0.035	-1000
TRAIL signaling pathway	0.0233	12	615	48	-0.001	0.063	1000	-1000	-0.028	-1000
Regulation of p38-alpha and p38-beta	0.0233	12	696	54	-0.055	0.056	1000	-1000	-0.048	-1000
Class I PI3K signaling events	0.0233	12	916	73	-0.074	0.048	1000	-1000	-0.037	-1000
Regulation of Telomerase	0.0233	12	1270	102	-0.13	0.065	1000	-1000	-0.042	-1000
ErbB4 signaling events	0.0213	11	813	69	-0.071	0.045	1000	-1000	-0.032	-1000
Insulin-mediated glucose transport	0.0213	11	378	32	-0.04	0.051	1000	-1000	-0.031	-1000
IFN-gamma pathway	0.0213	11	768	68	-0.099	0.056	1000	-1000	-0.042	-1000
PDGFR-beta signaling pathway	0.0213	11	1069	97	-0.072	0.072	1000	-1000	-0.04	-1000
Atypical NF-kappaB pathway	0.0194	10	319	31	-0.019	0.038	1000	-1000	-0.016	-1000
Insulin Pathway	0.0194	10	761	74	-0.071	0.062	1000	-1000	-0.037	-1000
Aurora A signaling	0.0174	9	543	60	-0.058	0.058	1000	-1000	-0.012	-1000
Nectin adhesion pathway	0.0174	9	614	63	-0.046	0.066	1000	-1000	-0.055	-1000
Signaling mediated by p38-gamma and p38-delta	0.0174	9	146	15	-0.016	0.026	1000	-1000	-0.026	-1000
Class I PI3K signaling events mediated by Akt	0.0155	8	607	68	-0.032	0.048	1000	-1000	-0.031	-1000
Signaling events mediated by HDAC Class I	0.0155	8	930	104	-0.06	0.059	1000	-1000	-0.029	-1000
Canonical NF-kappaB pathway	0.0136	7	299	39	-0.06	0.059	1000	-1000	-0.025	-1000
HIF-2-alpha transcription factor network	0.0136	7	331	43	-0.058	0.059	1000	-1000	-0.039	-1000
FoxO family signaling	0.0136	7	478	64	-0.033	0.079	1000	-1000	-0.053	-1000
IGF1 pathway	0.0136	7	425	57	-0.014	0.064	1000	-1000	-0.035	-1000
S1P3 pathway	0.0136	7	321	42	0	0.038	1000	-1000	-0.032	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0136	7	235	33	-0.029	0.065	1000	-1000	-0.033	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0116	6	797	125	-0.02	0.065	1000	-1000	-0.032	-1000
Arf6 trafficking events	0.0116	6	485	71	-0.05	0.048	1000	-1000	-0.021	-1000
Class IB PI3K non-lipid kinase events	0.0116	6	18	3	-0.02	0.02	1000	-1000	-0.008	-1000
p38 MAPK signaling pathway	0.0116	6	305	44	-0.018	0.042	1000	-1000	-0.031	-1000
Circadian rhythm pathway	0.0097	5	110	22	-0.007	0.038	1000	-1000	-0.035	-1000
Hedgehog signaling events mediated by Gli proteins	0.0097	5	367	65	-0.006	0.059	1000	-1000	-0.043	-1000
Arf6 downstream pathway	0.0097	5	254	43	-0.043	0.049	1000	-1000	-0.024	-1000
Signaling events mediated by HDAC Class II	0.0078	4	357	75	-0.094	0.071	1000	-1000	-0.016	-1000
PLK2 and PLK4 events	0.0078	4	12	3	0.001	-1000	1000	-1000	-0.012	-1000
mTOR signaling pathway	0.0078	4	260	53	-0.018	0.041	1000	-1000	-0.028	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0019	1	39	23	-0.001	0.05	1000	-1000	-0.028	-1000
Arf1 pathway	0.0019	1	60	54	-0.001	0.039	1000	-1000	-0.016	-1000
Alternative NF-kappaB pathway	0.0019	1	15	13	0	0.059	1000	-1000	0	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	16	27	0	0.061	1000	-1000	-0.023	-1000
Total	NA	3279	188474	7203	-10	-990	131000	-131000	-4.2	-131000

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.052	0.14	-10000	0	-0.28	126	126
EFNA5	-0.029	0.14	-10000	0	-0.43	48	48
FYN	-0.056	0.13	0.18	6	-0.29	100	106
neuron projection morphogenesis	-0.052	0.14	-10000	0	-0.28	126	126
cell-cell signaling	0	0	-10000	0	-10000	0	0
Ephrin A5/EPHA5	-0.052	0.14	-10000	0	-0.28	126	126
EPHA5	-0.063	0.16	-10000	0	-0.43	79	79

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IL23-mediated signaling events

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
CCL2	-0.42	0.54	-9999	-1.2	132	132
IL23A	-0.44	0.55	-9999	-1.2	140	140
NF kappa B1 p50/RelA/I kappa B alpha	-0.39	0.53	-9999	-1.2	130	130
positive regulation of T cell mediated cytotoxicity	-0.45	0.6	-9999	-1.3	140	140
ITGA3	-0.39	0.5	-9999	-1.2	121	121
IL17F	-0.26	0.32	-9999	-0.71	130	130
IL12B	-0.02	0.045	-9999	-0.16	5	5
STAT1 (dimer)	-0.43	0.57	-9999	-1.2	140	140
CD4	-0.37	0.49	-9999	-1.1	118	118
IL23	-0.42	0.53	-9999	-1.2	143	143
IL23R	-0.2	0.38	-9999	-1.1	75	75
IL1B	-0.46	0.59	-9999	-1.3	140	140
T-helper cell lineage commitment	0	0	-9999	-10000	0	0
IL24	-0.38	0.49	-9999	-1.1	121	121
TYK2	-0.007	0.035	-9999	-10000	0	0
STAT4	-0.064	0.16	-9999	-0.26	162	162
STAT3	0.026	0.003	-9999	-10000	0	0
IL18RAP	-0.023	0.13	-9999	-0.28	84	84
IL12RB1	-0.032	0.1	-9999	-0.37	34	34
PIK3CA	0.025	0.02	-9999	-0.43	1	1
IL12Rbeta1/TYK2	-0.022	0.082	-9999	-0.31	26	26
IL23R/JAK2	-0.19	0.36	-9999	-1.1	64	64
positive regulation of chronic inflammatory response	-0.45	0.6	-9999	-1.3	140	140
natural killer cell activation	0.005	0.007	-9999	-10000	0	0
JAK2	-0.008	0.042	-9999	-10000	0	0
PIK3R1	0.026	0.003	-9999	-10000	0	0
NFKB1	0.024	0.005	-9999	-10000	0	0
RELA	0.023	0.006	-9999	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.39	0.49	-9999	-1.1	148	148
ALOX12B	-0.45	0.55	-9999	-1.2	153	153
CXCL1	-0.43	0.54	-9999	-1.2	138	138
T cell proliferation	-0.45	0.6	-9999	-1.3	140	140
NFKBIA	0.024	0.005	-9999	-10000	0	0
IL17A	-0.2	0.25	-9999	-0.55	122	122
PI3K	-0.4	0.54	-9999	-1.2	137	137
IFNG	-0.018	0.031	-9999	-0.11	20	20
STAT3 (dimer)	-0.38	0.51	-9999	-1.1	131	131
IL18R1	-0.006	0.11	-9999	-0.42	27	27
IL23/IL23R/JAK2/TYK2/SOCS3	-0.26	0.36	-9999	-0.78	112	112
IL18/IL18R	-0.004	0.13	-9999	-0.29	76	76
macrophage activation	-0.019	0.02	-9999	-0.044	133	133
TNF	-0.46	0.59	-9999	-1.3	139	139
STAT3/STAT4	-0.43	0.55	-9999	-1.2	144	144
STAT4 (dimer)	-0.45	0.58	-9999	-1.2	145	145
IL18	0.002	0.093	-9999	-0.29	39	39
IL19	-0.38	0.48	-9999	-1.1	121	121
STAT5A (dimer)	-0.43	0.57	-9999	-1.2	138	138
STAT1	0.021	0.028	-9999	-0.13	16	16
SOCS3	-0.029	0.12	-9999	-0.43	30	30
CXCL9	-0.45	0.55	-9999	-1.2	151	151
MPO	-0.45	0.56	-9999	-1.2	153	153
positive regulation of humoral immune response	-0.45	0.6	-9999	-1.3	140	140
IL23/IL23R/JAK2/TYK2	-0.49	0.69	-9999	-1.4	136	136
IL6	-0.4	0.54	-9999	-1.2	125	125
STAT5A	0.016	0.066	-9999	-0.43	11	11
IL2	0.01	0.019	-9999	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0.005	0.007	-9999	-10000	0	0
CD3E	-0.43	0.55	-9999	-1.2	141	141
keratinocyte proliferation	-0.45	0.6	-9999	-1.3	140	140
NOS2	-0.4	0.51	-9999	-1.2	126	126

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.1	0.33	-10000	0	-0.97	62	62
MKNK1	0.022	0.01	-10000	0	-10000	0	0
MAPK14	-0.015	0.12	-10000	0	-0.29	74	74
ATF2/c-Jun	-0.021	0.1	-10000	0	-0.42	11	11
MAPK11	-0.024	0.13	-10000	0	-0.31	83	83
MITF	-0.026	0.14	0.3	1	-0.33	83	84
MAPKAPK5	-0.027	0.14	-10000	0	-0.34	83	83
KRT8	-0.064	0.18	-10000	0	-0.37	114	114
MAPKAPK3	0.025	0.021	-10000	0	-0.43	1	1
MAPKAPK2	0.026	0.004	-10000	0	-10000	0	0
p38alpha-beta/CK2	-0.03	0.18	-10000	0	-0.42	83	83
CEBPB	-0.034	0.16	-10000	0	-0.37	84	84
SLC9A1	-0.04	0.16	0.3	1	-0.39	81	82
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	-0.023	0.15	-10000	0	-0.33	85	85
p38alpha-beta/MNK1	-0.011	0.14	-10000	0	-0.33	81	81
JUN	-0.019	0.097	-10000	0	-0.42	11	11
PPARGC1A	-0.04	0.17	-10000	0	-0.38	91	91
USF1	-0.025	0.14	0.3	1	-0.34	81	82
RAB5/GDP/GDI1	-0.012	0.11	-10000	0	-0.25	83	83
NOS2	-0.054	0.23	-10000	0	-0.93	24	24
DDIT3	-0.026	0.14	0.22	1	-0.34	82	83
RAB5A	0.026	0.004	-10000	0	-10000	0	0
HSPB1	0.007	0.15	0.28	68	-0.28	75	143
p38alpha-beta/HBP1	-0.008	0.14	-10000	0	-0.33	71	71
CREB1	-0.03	0.15	-10000	0	-0.36	82	82
RAB5/GDP	0.019	0.003	-10000	0	-10000	0	0
EIF4E	-0.033	0.12	0.24	4	-0.3	75	79
RPS6KA4	-0.025	0.14	-10000	0	-0.34	80	80
PLA2G4A	-0.04	0.13	0.2	1	-0.33	76	77
GDI1	-0.026	0.14	-10000	0	-0.34	83	83
TP53	-0.053	0.17	-10000	0	-0.42	82	82
RPS6KA5	-0.033	0.15	-10000	0	-0.35	89	89
ESR1	-0.035	0.15	-10000	0	-0.35	89	89
HBP1	0.02	0.011	-10000	0	-10000	0	0
MEF2C	-0.028	0.14	-10000	0	-0.34	82	82
MEF2A	-0.028	0.14	-10000	0	-0.35	82	82
EIF4EBP1	-0.034	0.15	-10000	0	-0.36	81	81
KRT19	-0.062	0.18	-10000	0	-0.37	116	116
ELK4	-0.025	0.14	0.3	1	-0.34	81	82
ATF6	-0.025	0.14	0.3	1	-0.34	81	82
ATF1	-0.033	0.15	-10000	0	-0.37	84	84
p38alpha-beta/MAPKAPK2	0	0.15	-10000	0	-0.33	81	81
p38alpha-beta/MAPKAPK3	-0.002	0.15	-10000	0	-0.34	82	82

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	0.004	0.075	-10000	0	-0.25	30	30
NFATC2	-0.083	0.23	-10000	0	-0.57	60	60
NFATC3	-0.036	0.11	-10000	0	-0.27	67	67
CD40LG	-0.24	0.4	-10000	0	-0.94	106	106
ITCH	-0.024	0.091	-10000	0	-0.22	86	86
CBLB	-0.023	0.093	-10000	0	-0.44	2	2
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.2	0.36	-10000	0	-0.89	81	81
JUNB	0.007	0.072	-10000	0	-0.21	39	39
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.028	0.11	-10000	0	-0.26	87	87
T cell anergy	-0.066	0.16	0.26	1	-0.39	88	89
TLE4	-0.06	0.17	-10000	0	-0.5	44	44
Jun/NFAT1-c-4/p21SNFT	-0.2	0.44	-10000	0	-0.98	105	105
AP-1/NFAT1-c-4	-0.24	0.5	-10000	0	-1.1	106	106
IKZF1	-0.063	0.18	-10000	0	-0.58	39	39
T-helper 2 cell differentiation	-0.14	0.28	-10000	0	-0.81	48	48
AP-1/NFAT1	-0.063	0.18	-10000	0	-0.43	67	67
CALM1	-0.01	0.072	-10000	0	-0.2	2	2
EGR2	-0.24	0.51	-10000	0	-1.1	100	100
EGR3	-0.26	0.55	-10000	0	-1.3	94	94
NFAT1/FOXP3	-0.054	0.19	-10000	0	-0.47	56	56
EGR1	-0.043	0.14	-10000	0	-0.27	111	111
JUN	0.009	0.031	-10000	0	-0.14	9	9
EGR4	-0.088	0.17	-10000	0	-0.38	108	108
mol:Ca2+	-0.025	0.06	-10000	0	-0.15	88	88
GBP3	-0.079	0.22	-10000	0	-0.62	63	63
FOSL1	-0.028	0.13	-10000	0	-0.25	97	97
NFAT1-c-4/MAF/IRF4	-0.19	0.43	-10000	0	-0.96	106	106
DGKA	-0.057	0.16	-10000	0	-0.46	43	43
CREM	0.023	0.022	-10000	0	-0.43	1	1
NFAT1-c-4/PPARG	-0.2	0.44	-10000	0	-0.99	106	106
CTLA4	-0.079	0.19	-10000	0	-0.52	63	63
NFAT1-c-4 (dimer)/EGR1	-0.23	0.47	-10000	0	-1.1	106	106
NFAT1-c-4 (dimer)/EGR4	-0.24	0.46	-10000	0	-1	108	108
FOS	-0.041	0.14	-10000	0	-0.35	70	70
IFNG	-0.1	0.21	-10000	0	-0.66	35	35
T cell activation	-0.11	0.23	-10000	0	-0.69	35	35
MAF	0.024	0.035	-10000	0	-0.43	3	3
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.18	0.38	0.84	106	-10000	0	106
TNF	-0.3	0.44	-10000	0	-0.99	124	124
FASLG	-0.26	0.55	-10000	0	-1.3	101	101
TBX21	-0.004	0.099	-10000	0	-0.39	27	27
BATF3	0.001	0.091	-10000	0	-0.26	45	45
PRKCQ	0.015	0.061	-10000	0	-0.43	9	9
PTPN1	-0.058	0.16	-10000	0	-0.48	36	36
NFAT1-c-4/ICER1	-0.19	0.43	-10000	0	-0.97	105	105
GATA3	-0.038	0.14	-10000	0	-0.43	49	49
T-helper 1 cell differentiation	-0.1	0.2	-10000	0	-0.64	37	37
IL2RA	-0.17	0.32	-10000	0	-0.82	69	69
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.055	0.16	-10000	0	-0.46	41	41
E2F1	0.017	0.057	-10000	0	-0.36	8	8
PPARG	0.009	0.081	-10000	0	-0.43	16	16
SLC3A2	-0.055	0.16	-10000	0	-0.48	38	38
IRF4	-0.006	0.1	-10000	0	-0.28	53	53
PTGS2	-0.26	0.43	-10000	0	-1	109	109
CSF2	-0.24	0.39	-10000	0	-0.95	106	106
JunB/Fra1/NFAT1-c-4	-0.2	0.43	-10000	0	-0.96	105	105
IL4	-0.15	0.3	-10000	0	-0.87	46	46
IL5	-0.24	0.4	-10000	0	-0.94	106	106
IL2	-0.12	0.23	-10000	0	-0.71	33	33
IL3	-0.024	0.082	-10000	0	-0.65	4	4
RNF128	-0.085	0.2	-10000	0	-0.52	88	88
NFATC1	-0.18	0.38	-10000	0	-0.85	106	106
CDK4	0.11	0.21	0.59	47	-10000	0	47
PTPRK	-0.057	0.16	-10000	0	-0.49	38	38
IL8	-0.26	0.42	-10000	0	-0.97	114	114
POU2F1	0.025	0.02	-10000	0	-0.43	1	1

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.18	0.49	-9999	-1.1	84	84
PLK1	0.006	0.15	-9999	-1.3	6	6
BIRC5	-0.19	0.51	-9999	-1.4	75	75
HSPA1B	-0.19	0.5	-9999	-1.2	83	83
MAP2K1	0.01	0.045	-9999	-0.18	1	1
BRCA2	-0.19	0.51	-9999	-1.2	83	83
FOXM1	-0.27	0.7	-9999	-1.7	85	85
XRCC1	-0.18	0.49	-9999	-1.2	77	77
FOXM1B/p19	-0.19	0.5	-9999	-1.2	83	83
Cyclin D1/CDK4	-0.17	0.45	-9999	-1	83	83
CDC2	-0.19	0.52	-9999	-1.2	85	85
TGFA	-0.16	0.44	-9999	-1	86	86
SKP2	-0.19	0.5	-9999	-1.2	81	81
CCNE1	0.016	0.022	-9999	-0.14	2	2
CKS1B	-0.18	0.49	-9999	-1.1	87	87
RB1	-0.1	0.32	-9999	-0.85	56	56
FOXM1C/SP1	-0.22	0.59	-9999	-1.4	87	87
AURKB	-0.23	0.56	-9999	-1.4	90	90
CENPF	-0.2	0.52	-9999	-1.3	77	77
CDK4	0.014	0.026	-9999	-10000	0	0
MYC	-0.16	0.43	-9999	-0.99	88	88
CHEK2	0.004	0.066	-9999	-0.37	6	6
ONECUT1	-0.18	0.47	-9999	-1.1	85	85
CDKN2A	-0.012	0.11	-9999	-0.3	55	55
LAMA4	-0.18	0.49	-9999	-1.2	79	79
FOXM1B/HNF6	-0.23	0.58	-9999	-1.4	85	85
FOS	-0.26	0.56	-9999	-1.2	124	124
SP1	0.025	0.009	-9999	-10000	0	0
CDC25B	-0.18	0.49	-9999	-1.2	78	78
response to radiation	0	0.026	-9999	-10000	0	0
CENPB	-0.18	0.49	-9999	-1.2	79	79
CENPA	-0.21	0.53	-9999	-1.3	84	84
NEK2	-0.23	0.56	-9999	-1.3	92	92
HIST1H2BA	-0.18	0.48	-9999	-1.2	80	80
CCNA2	-0.012	0.1	-9999	-0.24	63	63
EP300	0.022	0.04	-9999	-0.43	4	4
CCNB1/CDK1	-0.22	0.59	-9999	-1.5	78	78
CCNB2	-0.23	0.57	-9999	-1.4	89	89
CCNB1	-0.19	0.52	-9999	-1.3	79	79
ETV5	-0.19	0.49	-9999	-1.2	84	84
ESR1	-0.2	0.5	-9999	-1.2	89	89
CCND1	-0.18	0.46	-9999	-1.1	84	84
GSK3A	0.012	0.037	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	0.012	0.091	-9999	-0.3	26	26
CDK2	0.014	0.049	-9999	-0.29	8	8
G2/M transition of mitotic cell cycle	-0.003	0.03	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.2	0.55	-9999	-1.3	86	86
GAS1	-0.18	0.49	-9999	-1.2	78	78
MMP2	-0.19	0.5	-9999	-1.2	82	82
RB1/FOXM1C	-0.19	0.48	-9999	-1.1	85	85
CREBBP	0.026	0.003	-9999	-10000	0	0

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.071	0.19	-10000	0	-0.41	101	101
STMN1	-0.047	0.12	0.18	3	-0.31	76	79
Aurora B/RasGAP/Survivin	-0.057	0.19	-10000	0	-0.33	137	137
Chromosomal passenger complex/Cul3 protein complex	-0.069	0.15	-10000	0	-0.35	87	87
BIRC5	-0.064	0.17	-10000	0	-0.43	80	80
DES	-0.26	0.45	-10000	0	-0.86	167	167
Aurora C/Aurora B/INCENP	-0.013	0.11	-10000	0	-0.24	94	94
Aurora B/TACC1	-0.027	0.11	-10000	0	-0.26	87	87
Aurora B/PP2A	-0.034	0.13	-10000	0	-0.31	87	87
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	-0.019	0.059	-10000	0	-0.14	92	92
mitotic metaphase/anaphase transition	0.001	0.005	-10000	0	-10000	0	0
NDC80	-0.095	0.19	0.19	6	-0.36	145	151
Cul3 protein complex	0.046	0.027	-10000	0	-0.26	2	2
KIF2C	-0.093	0.25	-10000	0	-0.48	104	104
PEBP1	0.015	0.04	-10000	0	-0.44	3	3
KIF20A	-0.079	0.17	-10000	0	-0.43	93	93
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	-0.035	0.13	-10000	0	-0.31	88	88
SEPT1	0.024	0.024	-10000	0	-0.19	5	5
SMC2	0.026	0.004	-10000	0	-10000	0	0
SMC4	0.017	0.036	-10000	0	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.12	0.3	0.24	1	-0.76	90	91
PSMA3	0.026	0.004	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.003	-10000	0	-10000	0	0
H3F3B	-0.043	0.12	0.12	1	-0.3	88	89
AURKB	-0.074	0.18	-10000	0	-0.31	151	151
AURKC	0.011	0.051	-10000	0	-0.18	26	26
CDCA8	-0.01	0.075	-10000	0	-0.18	62	62
cytokinesis	-0.16	0.32	0.22	2	-0.73	109	111
Aurora B/Septin1	-0.13	0.32	0.26	2	-0.7	105	107
AURKA	0.018	0.038	-10000	0	-0.15	22	22
INCENP	0.015	0.029	-10000	0	-0.44	1	1
KLHL13	0.025	0.028	-10000	0	-0.43	2	2
BUB1	-0.043	0.15	-10000	0	-0.31	97	97
hSgo1/Aurora B/Survivin	-0.083	0.22	-10000	0	-0.37	161	161
EVI5	0.021	0.01	-10000	0	-10000	0	0
RhoA/GTP	-0.11	0.29	-10000	0	-0.63	103	103
SGOL1	-0.047	0.15	-10000	0	-0.28	122	122
CENPA	-0.1	0.25	0.18	2	-0.56	102	104
NCAPG	-0.061	0.16	-10000	0	-0.43	77	77
Aurora B/HC8 Proteasome	-0.035	0.13	-10000	0	-0.31	88	88
NCAPD2	0.024	0.007	-10000	0	-10000	0	0
Aurora B/PP1-gamma	-0.035	0.13	-10000	0	-0.31	88	88
RHOA	0.026	0.004	-10000	0	-10000	0	0
NCAPH	-0.015	0.12	-10000	0	-0.26	73	73
NPM1	-0.083	0.2	-10000	0	-0.5	94	94
RASA1	0.026	0.003	-10000	0	-10000	0	0
KLHL9	0.024	0.008	-10000	0	-10000	0	0
mitotic prometaphase	-0.004	0.007	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.035	0.13	-10000	0	-0.31	88	88
PPP1CC	0.026	0.003	-10000	0	-10000	0	0
Centraspindlin	-0.13	0.31	0.2	1	-0.67	106	107
RhoA/GDP	0.019	0.003	-10000	0	-10000	0	0
NSUN2	-0.082	0.2	-10000	0	-0.51	91	91
MYLK	-0.049	0.12	-10000	0	-0.29	98	98
KIF23	-0.036	0.13	-10000	0	-0.25	108	108
VIM	-0.081	0.15	0.18	6	-0.32	128	134
RACGAP1	0.017	0.022	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
NCL	-0.085	0.21	-10000	0	-0.53	90	90
Chromosomal passenger complex	-0.13	0.29	0.19	1	-0.64	107	108
Chromosomal passenger complex/EVI5	-0.043	0.19	-10000	0	-0.32	140	140
TACC1	0.025	0.005	-10000	0	-10000	0	0
PPP2R5D	0.026	0.002	-10000	0	-10000	0	0
CUL3	0.026	0.003	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

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	-0.008	0.071	-10000	0	-0.39	11	11
Crk/p130 Cas/Paxillin	-0.051	0.12	-10000	0	-0.28	76	76
JUN	-0.061	0.14	-10000	0	-0.27	119	119
HRAS	0.025	0.006	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.018	0.15	-10000	0	-0.28	111	111
RAP1A	0.021	0.01	-10000	0	-10000	0	0
FRS2	0.026	0.004	-10000	0	-10000	0	0
RAP1A/GDP	0.016	0.008	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.025	0.16	-10000	0	-0.28	133	133
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.026	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.026	0.002	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.004	0.12	-10000	0	-0.26	86	86
RHOA	0.026	0.004	-10000	0	-10000	0	0
RAP1A/GTP	-0.038	0.15	-10000	0	-0.26	135	135
GRB7	0.001	0.044	-10000	0	-0.13	41	41
RET51/GFRalpha1/GDNF	-0.019	0.15	-10000	0	-0.28	121	121
MAPKKK cascade	-0.049	0.14	-10000	0	-0.28	125	125
BCAR1	0.025	0.02	-10000	0	-0.43	1	1
RET9/GFRalpha1/GDNF/IRS1	-0.003	0.12	-10000	0	-0.26	84	84
lamellipodium assembly	-0.036	0.1	-10000	0	-0.26	65	65
RET51/GFRalpha1/GDNF/SHC	-0.023	0.16	-10000	0	-0.28	127	127
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
RET9/GFRalpha1/GDNF/SHC	-0.003	0.12	-10000	0	-0.26	83	83
RET9/GFRalpha1/GDNF/Shank3	-0.006	0.12	-10000	0	-0.26	88	88
MAPK3	-0.074	0.12	0.17	5	-0.26	123	128
DOK1	0.025	0.021	-10000	0	-0.28	2	2
DOK6	-0.017	0.13	-10000	0	-0.43	46	46
PXN	0.026	0.004	-10000	0	-10000	0	0
neurite development	-0.067	0.13	-10000	0	-0.36	52	52
DOK5	0.016	0.066	-10000	0	-0.43	11	11
GFRA1	-0.015	0.12	-10000	0	-0.31	61	61
MAPK8	-0.062	0.14	-10000	0	-0.28	133	133
HRAS/GTP	-0.035	0.17	-10000	0	-0.3	132	132
tube development	0	0.12	0.2	14	-0.25	82	96
MAPK1	-0.074	0.12	0.17	5	-0.26	124	129
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.024	0.11	-10000	0	-0.25	82	82
Rac1/GDP	0.017	0.007	-10000	0	-10000	0	0
SRC	0.025	0.005	-10000	0	-10000	0	0
PDLIM7	0.023	0.021	-10000	0	-0.13	9	9
RET51/GFRalpha1/GDNF/Dok6	-0.028	0.18	-10000	0	-0.31	133	133
SHC1	0.024	0.014	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.032	0.17	-10000	0	-0.29	138	138
RET51/GFRalpha1/GDNF/Dok5	-0.026	0.16	-10000	0	-0.28	131	131
PRKCA	0.024	0.021	-10000	0	-0.43	1	1
HRAS/GDP	0.018	0.005	-10000	0	-10000	0	0
CREB1	-0.041	0.14	-10000	0	-0.31	85	85
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.025	0.11	-10000	0	-0.26	81	81
RET51/GFRalpha1/GDNF/Grb7	-0.028	0.16	-10000	0	-0.28	135	135
mol:GDP	0	0	-10000	0	-10000	0	0
RET	-0.044	0.15	-10000	0	-0.3	107	107
DOK4	0.012	0.079	-10000	0	-0.43	16	16
JNK cascade	-0.062	0.13	0.19	1	-0.4	44	45
RET9/GFRalpha1/GDNF/FRS2	-0.004	0.12	-10000	0	-0.26	86	86
SHANK3	0.021	0.035	-10000	0	-0.19	10	10
RASA1	0.026	0.003	-10000	0	-10000	0	0
NCK1	0.025	0.02	-10000	0	-0.43	1	1
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.023	0.1	-10000	0	-0.25	81	81
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.053	0.15	-10000	0	-0.28	130	130
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.056	0.15	-10000	0	-0.28	134	134
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.051	0.15	-10000	0	-0.28	123	123
PI3K	-0.06	0.16	0.23	1	-0.38	81	82
SOS1	0.026	0.002	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	0.006	0.12	-10000	0	-0.25	82	82
GRB10	0.021	0.03	-10000	0	-0.43	2	2
activation of MAPKK activity	-0.052	0.14	-10000	0	-0.34	85	85
RET51/GFRalpha1/GDNF/FRS2	-0.025	0.16	-10000	0	-0.28	134	134
GAB1	0.025	0.02	-10000	0	-0.43	1	1
IRS1	0.026	0.003	-10000	0	-10000	0	0
IRS2	0.024	0.021	-10000	0	-0.43	1	1
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.053	0.15	-10000	0	-0.29	123	123
RET51/GFRalpha1/GDNF/PKC alpha	-0.025	0.16	-10000	0	-0.28	129	129
GRB2	0.025	0.006	-10000	0	-10000	0	0
PRKACA	0.025	0.005	-10000	0	-10000	0	0
GDNF	-0.034	0.15	-10000	0	-0.38	73	73
RAC1	0.023	0.009	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.023	0.16	-10000	0	-0.28	131	131
Rac1/GTP	-0.037	0.12	-10000	0	-0.3	63	63
RET9/GFRalpha1/GDNF	-0.028	0.12	-10000	0	-0.28	86	86
GFRalpha1/GDNF	-0.035	0.14	-10000	0	-0.34	86	86

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.073	0.13	-10000	0	-0.35	61	61
TBX21	-0.33	0.46	-10000	0	-1.1	121	121
B2M	0.025	0.016	-10000	0	-0.13	5	5
TYK2	-0.002	0.034	-10000	0	-10000	0	0
IL12RB1	-0.027	0.1	-10000	0	-0.37	33	33
GADD45B	-0.24	0.36	-10000	0	-0.85	85	85
IL12RB2	-0.049	0.12	-10000	0	-0.28	74	74
GADD45G	-0.25	0.38	-10000	0	-1	68	68
natural killer cell activation	-0.012	0.02	-10000	0	-0.043	80	80
RELB	0.02	0.025	-10000	0	-0.43	1	1
RELA	0.025	0.005	-10000	0	-10000	0	0
IL18	-0.005	0.095	-10000	0	-0.3	38	38
IL2RA	-0.015	0.071	-10000	0	-0.43	8	8
IFNG	-0.008	0.021	-10000	0	-0.13	5	5
STAT3 (dimer)	-0.24	0.33	-10000	0	-0.73	128	128
HLA-DRB5	-0.002	0.006	-10000	0	-0.02	41	41
FASLG	-0.3	0.42	-10000	0	-0.98	111	111
NF kappa B2 p52/RelB	-0.29	0.43	-10000	0	-0.93	128	128
CD4	0.017	0.035	-10000	0	-0.23	6	6
SOCS1	0.008	0.068	-10000	0	-0.43	8	8
EntrezGene:6955	-0.001	0.007	-10000	0	-0.023	41	41
CD3D	-0.033	0.12	-10000	0	-0.38	39	39
CD3E	-0.052	0.14	-10000	0	-0.26	130	130
CD3G	0.004	0.044	-10000	0	-0.15	2	2
IL12Rbeta2/JAK2	-0.029	0.096	-10000	0	-0.28	44	44
CCL3	-0.4	0.55	-10000	0	-1.3	128	128
CCL4	-0.39	0.56	-10000	0	-1.3	124	124
HLA-A	0	0.003	-10000	0	-0.049	1	1
IL18/IL18R	-0.021	0.14	-10000	0	-0.31	76	76
NOS2	-0.28	0.41	-10000	0	-0.96	103	103
IL12/IL12R/TYK2/JAK2/SPHK2	-0.067	0.13	-10000	0	-0.36	57	57
IL1R1	-0.32	0.44	-10000	0	-1	107	107
IL4	0.017	0.034	-10000	0	-10000	0	0
JAK2	-0.003	0.034	-10000	0	-10000	0	0
EntrezGene:6957	-0.001	0.007	-10000	0	-0.021	40	40
TCR/CD3/MHC I/CD8	-0.046	0.12	-10000	0	-0.4	35	35
RAB7A	-0.19	0.3	0.52	1	-0.74	65	66
lysosomal transport	-0.18	0.28	0.51	1	-0.69	67	68
FOS	-0.23	0.44	-10000	0	-1.2	70	70
STAT4 (dimer)	-0.28	0.38	0.5	1	-0.83	129	130
STAT5A (dimer)	-0.3	0.43	-10000	0	-0.92	135	135
GZMA	-0.37	0.5	-10000	0	-1.1	133	133
GZMB	-0.36	0.49	-10000	0	-1.1	127	127
HLX	0.018	0.046	-10000	0	-0.21	16	16
LCK	-0.34	0.47	-10000	0	-1	135	135
TCR/CD3/MHC II/CD4	-0.038	0.1	-10000	0	-0.26	56	56
IL2/IL2R	0.002	0.11	-10000	0	-0.24	68	68
MAPK14	-0.24	0.36	-10000	0	-0.83	95	95
CCR5	-0.28	0.42	-10000	0	-1	87	87
IL1B	-0.094	0.16	-10000	0	-0.28	173	173
STAT6	-0.072	0.11	-10000	0	-0.48	4	4
STAT4	-0.064	0.16	-10000	0	-0.26	162	162
STAT3	0.026	0.003	-10000	0	-10000	0	0
STAT1	0.021	0.028	-10000	0	-0.13	16	16
NFKB1	0.026	0.004	-10000	0	-10000	0	0
NFKB2	0.023	0.03	-10000	0	-0.33	3	3
IL12B	-0.012	0.038	-10000	0	-0.15	6	6
CD8A	-0.024	0.13	-10000	0	-0.29	83	83
CD8B	-0.002	0.1	-10000	0	-0.32	42	42
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.073	0.13	0.35	61	-10000	0	61
IL2RB	-0.028	0.13	-10000	0	-0.43	39	39
proteasomal ubiquitin-dependent protein catabolic process	-0.26	0.34	0.49	1	-0.75	129	130
IL2RG	0.001	0.087	-10000	0	-0.22	52	52
IL12	-0.019	0.084	-10000	0	-0.34	22	22
STAT5A	0.016	0.066	-10000	0	-0.43	11	11
CD247	0.008	0.065	-10000	0	-0.21	30	30
IL2	-0.014	0.009	-10000	0	-10000	0	0
SPHK2	0.021	0.01	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.024	0.1	-10000	0	-0.43	25	25
IL12/IL12R/TYK2/JAK2	-0.36	0.52	-10000	0	-1.1	134	134
MAP2K3	-0.24	0.36	-10000	0	-0.81	102	102
RIPK2	0.024	0.007	-10000	0	-10000	0	0
MAP2K6	-0.24	0.36	-10000	0	-0.8	108	108
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.002	0.007	-10000	0	-0.023	43	43
IL18RAP	-0.032	0.13	-10000	0	-0.3	76	76
IL12Rbeta1/TYK2	-0.017	0.086	-10000	0	-0.33	25	25
EOMES	0.022	0.097	-10000	0	-0.8	5	5
STAT1 (dimer)	-0.24	0.32	-10000	0	-0.73	120	120
T cell proliferation	-0.2	0.27	0.49	1	-0.6	118	119
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.014	0.11	-10000	0	-0.41	30	30
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.23	0.3	-10000	0	-0.66	124	124
ATF2	-0.22	0.33	0.51	1	-0.76	96	97

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.046	0.17	0.23	19	-0.36	78	97
FYN	-0.072	0.2	0.25	18	-0.44	89	107
LAT/GRAP2/SLP76	-0.074	0.17	0.23	5	-0.39	80	85
IKBKB	0.025	0.005	-10000	0	-10000	0	0
AKT1	-0.057	0.15	0.22	20	-0.33	83	103
B2M	0.021	0.021	-10000	0	-0.14	5	5
IKBKG	-0.013	0.051	0.092	17	-0.12	28	45
MAP3K8	0.016	0.047	-10000	0	-0.2	17	17
mol:Ca2+	-0.016	0.027	0.089	12	-0.07	40	52
integrin-mediated signaling pathway	0.022	0.039	-10000	0	-0.24	9	9
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.081	0.2	0.25	16	-0.44	88	104
TRPV6	0.21	0.52	1.1	116	-0.45	39	155
CD28	-0.023	0.12	-10000	0	-0.28	80	80
SHC1	-0.074	0.19	0.23	25	-0.4	98	123
receptor internalization	-0.059	0.15	0.24	2	-0.38	67	69
PRF1	-0.11	0.33	-10000	0	-0.96	55	55
KRAS	0.025	0.005	-10000	0	-10000	0	0
GRB2	0.025	0.006	-10000	0	-10000	0	0
COT/AKT1	-0.043	0.13	0.21	17	-0.28	76	93
LAT	-0.084	0.19	0.23	16	-0.42	96	112
EntrezGene:6955	-0.002	0.006	-10000	0	-10000	0	0
CD3D	-0.035	0.12	-10000	0	-0.38	41	41
CD3E	-0.052	0.15	-10000	0	-0.27	127	127
CD3G	0.001	0.044	-10000	0	-10000	0	0
RASGRP2	-0.003	0.019	0.13	1	-0.16	2	3
RASGRP1	-0.065	0.16	0.26	17	-0.35	86	103
HLA-A	-0.002	0.006	-10000	0	-10000	0	0
RASSF5	0.016	0.062	-10000	0	-0.3	16	16
RAP1A/GTP/RAPL	0.023	0.039	-10000	0	-0.24	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.001	0.065	0.16	35	-0.12	17	52
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.038	0.067	-10000	0	-0.18	62	62
PRKCA	-0.045	0.088	0.15	5	-0.22	61	66
GRAP2	-0.007	0.1	-10000	0	-0.43	25	25
mol:IP3	-0.063	0.14	0.18	18	-0.31	87	105
EntrezGene:6957	-0.002	0.006	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.055	0.14	-10000	0	-0.36	61	61
ORAI1	-0.18	0.43	0.44	14	-0.95	114	128
CSK	-0.076	0.19	0.22	18	-0.41	98	116
B7 family/CD28	-0.065	0.21	0.26	8	-0.45	87	95
CHUK	0.025	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.09	0.2	0.26	1	-0.44	100	101
PTPN6	-0.085	0.19	0.22	4	-0.42	95	99
VAV1	-0.078	0.2	0.21	24	-0.41	103	127
Monovalent TCR/CD3	-0.044	0.11	-10000	0	-0.27	88	88
CBL	0.025	0.007	-10000	0	-10000	0	0
LCK	-0.089	0.22	0.25	18	-0.45	104	122
PAG1	-0.073	0.19	0.21	27	-0.41	96	123
RAP1A	0.021	0.01	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.089	0.2	0.26	1	-0.44	97	98
CD80	-0.001	0.073	-10000	0	-0.18	55	55
CD86	0	0.1	-10000	0	-0.43	25	25
PDK1/CARD11/BCL10/MALT1	-0.04	0.084	-10000	0	-0.21	66	66
HRAS	0.025	0.006	-10000	0	-10000	0	0
GO:0035030	-0.078	0.17	0.21	17	-0.38	91	108
CD8A	-0.027	0.13	-10000	0	-0.29	83	83
CD8B	-0.006	0.1	-10000	0	-0.33	42	42
PTPRC	-0.004	0.1	-10000	0	-0.43	24	24
PDK1/PKC theta	-0.065	0.18	0.29	15	-0.4	80	95
CSK/PAG1	-0.074	0.18	0.21	19	-0.4	93	112
SOS1	0.026	0.002	-10000	0	-10000	0	0
peptide-MHC class I	0.013	0.019	-10000	0	-0.091	4	4
GRAP2/SLP76	-0.073	0.19	0.23	10	-0.41	96	106
STIM1	-0.008	0.2	1.2	10	-0.89	2	12
RAS family/GTP	-0.011	0.08	0.18	22	-0.17	35	57
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.063	0.16	-10000	0	-0.4	67	67
mol:DAG	-0.07	0.11	0.13	2	-0.27	99	101
RAP1A/GDP	0.004	0.027	0.077	22	-0.062	5	27
PLCG1	0.025	0.005	-10000	0	-10000	0	0
CD247	0.008	0.065	-10000	0	-0.21	30	30
cytotoxic T cell degranulation	-0.1	0.31	-10000	0	-0.9	56	56
RAP1A/GTP	0	0.007	-10000	0	-0.05	4	4
mol:PI-3-4-5-P3	-0.067	0.17	0.24	17	-0.38	86	103
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.078	0.17	0.22	10	-0.39	85	95
NRAS	0.021	0.01	-10000	0	-10000	0	0
ZAP70	-0.004	0.098	-10000	0	-0.43	22	22
GRB2/SOS1	0.037	0.009	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.087	0.16	0.2	1	-0.38	87	88
MALT1	0.026	0.004	-10000	0	-10000	0	0
TRAF6	0.024	0.021	-10000	0	-0.43	1	1
CD8 heterodimer	-0.023	0.13	-10000	0	-0.3	81	81
CARD11	0.012	0.067	-10000	0	-0.43	11	11
PRKCB	-0.053	0.093	0.15	6	-0.22	74	80
PRKCE	-0.047	0.09	0.15	6	-0.22	66	72
PRKCQ	-0.074	0.2	0.28	14	-0.43	86	100
LCP2	0.02	0.033	-10000	0	-0.15	15	15
BCL10	0.021	0.01	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.048	0.13	0.21	21	-0.29	81	102
IKK complex	-0.003	0.057	0.17	20	-0.11	7	27
RAS family/GDP	-0.005	0.01	-10000	0	-10000	0	0
MAP3K14	-0.034	0.1	0.17	19	-0.22	66	85
PDPK1	-0.055	0.15	0.23	20	-0.32	81	101
TCR/CD3/MHC I/CD8/Fyn	-0.09	0.22	0.23	1	-0.51	87	88

×

Syndecan-1-mediated signaling events

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
TGFB1	0.021	0.022	-10000	0	-0.43	1	1
CCL5	-0.025	0.12	-10000	0	-0.43	39	39
SDCBP	0.025	0.006	-10000	0	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.065	0.14	0.24	6	-0.31	80	86
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
Syndecan-1/Laminin-5	-0.056	0.14	0.2	10	-0.34	59	69
Syndecan-1/Syntenin	-0.048	0.14	0.24	15	-0.34	57	72
MAPK3	-0.051	0.13	0.2	14	-0.37	40	54
HGF/MET	-0.04	0.12	-10000	0	-0.28	83	83
TGFB1/TGF beta receptor Type II	0.021	0.022	-10000	0	-0.43	1	1
BSG	0.025	0.007	-10000	0	-10000	0	0
keratinocyte migration	-0.055	0.14	0.2	10	-0.34	59	69
Syndecan-1/RANTES	-0.068	0.16	0.24	15	-0.38	67	82
Syndecan-1/CD147	-0.043	0.14	0.24	4	-0.37	43	47
Syndecan-1/Syntenin/PIP2	-0.047	0.14	0.24	12	-0.34	54	66
LAMA5	0.024	0.022	-10000	0	-0.28	2	2
positive regulation of cell-cell adhesion	-0.047	0.14	0.23	12	-0.33	54	66
MMP7	-0.073	0.16	-10000	0	-0.29	150	150
HGF	-0.009	0.091	-10000	0	-0.2	69	69
Syndecan-1/CASK	-0.069	0.13	-10000	0	-0.3	81	81
Syndecan-1/HGF/MET	-0.075	0.16	0.24	4	-0.35	88	92
regulation of cell adhesion	-0.043	0.14	0.26	25	-0.36	39	64
HPSE	-0.014	0.12	-10000	0	-0.43	39	39
positive regulation of cell migration	-0.065	0.14	0.24	6	-0.31	80	86
SDC1	-0.063	0.14	0.19	2	-0.31	85	87
Syndecan-1/Collagen	-0.065	0.14	0.24	6	-0.31	80	86
PPIB	0.026	0.003	-10000	0	-10000	0	0
MET	-0.047	0.14	-10000	0	-0.43	52	52
PRKACA	0.025	0.005	-10000	0	-10000	0	0
MMP9	-0.041	0.13	-10000	0	-0.23	133	133
MAPK1	-0.051	0.13	0.2	13	-0.36	40	53
homophilic cell adhesion	-0.061	0.14	0.22	15	-0.32	74	89
MMP1	-0.008	0.048	-10000	0	-0.43	1	1

×

Thromboxane A2 receptor signaling

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
TGM2	0.023	0.016	-10000	0	-10000	0	0
GNB1/GNG2	-0.055	0.077	-10000	0	-0.18	125	125
AKT1	-0.032	0.12	0.3	8	-0.27	30	38
EGF	-0.01	0.11	-10000	0	-0.43	33	33
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.013	0.074	0.33	18	-0.22	2	20
mol:Ca2+	-0.051	0.16	0.33	7	-0.29	127	134
LYN	0.009	0.081	0.32	19	-0.24	4	23
RhoA/GTP	-0.025	0.062	-10000	0	-0.13	112	112
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.067	0.18	0.31	11	-0.35	128	139
GNG2	0.022	0.04	-10000	0	-0.43	4	4
ARRB2	0.026	0.002	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.001	0.099	-10000	0	-0.4	21	21
G beta5/gamma2	-0.065	0.1	-10000	0	-0.24	123	123
PRKCH	-0.064	0.17	0.33	7	-0.34	125	132
DNM1	-0.027	0.12	-10000	0	-0.22	108	108
TXA2/TP beta/beta Arrestin3	-0.008	0.045	-10000	0	-10000	0	0
mol:GTP	0	0.002	-10000	0	-10000	0	0
PTGDR	0.003	0.063	-10000	0	-0.16	52	52
G12 family/GTP	-0.067	0.14	-10000	0	-0.3	116	116
ADRBK1	0.025	0.005	-10000	0	-10000	0	0
ADRBK2	0.024	0.029	-10000	0	-0.33	3	3
RhoA/GTP/ROCK1	0.034	0.007	-10000	0	-10000	0	0
mol:GDP	0.023	0.11	0.29	21	-0.31	9	30
mol:NADP	0.017	0.034	-10000	0	-0.28	4	4
RAB11A	0.026	0.003	-10000	0	-10000	0	0
PRKG1	-0.009	0.12	-10000	0	-0.38	43	43
mol:IP3	-0.068	0.19	0.35	7	-0.37	127	134
cell morphogenesis	0.033	0.007	-10000	0	-10000	0	0
PLCB2	-0.1	0.25	0.39	6	-0.5	126	132
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.009	0.088	0.31	16	-0.21	12	28
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0	0.071	0.3	9	-0.25	9	18
RHOA	0.026	0.004	-10000	0	-10000	0	0
PTGIR	0.012	0.049	-10000	0	-0.19	22	22
PRKCB1	-0.07	0.18	0.33	6	-0.36	128	134
GNAQ	0.026	0.004	-10000	0	-10000	0	0
mol:L-citrulline	0.017	0.034	-10000	0	-0.28	4	4
TXA2/TXA2-R family	-0.11	0.25	0.39	6	-0.52	129	135
LCK	-0.001	0.085	0.34	16	-0.23	2	18
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.005	0.048	-10000	0	-0.2	9	9
TXA2-R family/G12 family/GDP/G beta/gamma	-0.048	0.17	-10000	0	-0.43	80	80
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.009	0.049	-10000	0	-0.2	9	9
MAPK14	-0.041	0.12	0.26	11	-0.23	125	136
TGM2/GTP	-0.081	0.2	0.38	3	-0.41	126	129
MAPK11	-0.043	0.12	0.26	11	-0.23	126	137
ARHGEF1	-0.036	0.083	0.14	1	-0.18	113	114
GNAI2	0.025	0.005	-10000	0	-10000	0	0
JNK cascade	-0.076	0.19	0.35	7	-0.38	129	136
RAB11/GDP	0.026	0.006	-10000	0	-10000	0	0
ICAM1	-0.054	0.15	0.3	6	-0.28	131	137
cAMP biosynthetic process	-0.066	0.18	0.35	7	-0.34	127	134
Gq family/GTP/EBP50	0.005	0.07	0.24	8	-0.22	33	41
actin cytoskeleton reorganization	0.033	0.007	-10000	0	-10000	0	0
SRC	0.004	0.063	0.3	9	-0.23	2	11
GNB5	0.026	0.003	-10000	0	-10000	0	0
GNB1	0.022	0.01	-10000	0	-10000	0	0
EGF/EGFR	-0.011	0.12	0.33	27	-0.26	33	60
VCAM1	-0.076	0.18	0.3	6	-0.36	131	137
TP beta/Gq family/GDP/G beta5/gamma2	-0.001	0.099	-10000	0	-0.4	21	21
platelet activation	-0.053	0.16	0.32	12	-0.3	129	141
PGI2/IP	0.01	0.034	-10000	0	-0.12	22	22
PRKACA	0.004	0.037	-10000	0	-0.23	8	8
Gq family/GDP/G beta5/gamma2	-0.001	0.094	-10000	0	-0.37	22	22
TXA2/TP beta/beta Arrestin2	-0.021	0.12	-10000	0	-0.48	33	33
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.002	0.036	-10000	0	-0.22	9	9
mol:DAG	-0.078	0.21	0.37	6	-0.4	127	133
EGFR	-0.016	0.12	-10000	0	-0.4	46	46
TXA2/TP alpha	-0.093	0.23	0.41	6	-0.46	126	132
Gq family/GTP	-0.002	0.063	0.21	5	-0.21	35	40
YES1	0.009	0.078	0.34	16	-0.23	4	20
GNAI2/GTP	0.003	0.045	-10000	0	-0.2	9	9
PGD2/DP	0.005	0.043	-10000	0	-0.1	52	52
SLC9A3R1	0.022	0.04	-10000	0	-0.43	4	4
FYN	0.01	0.077	0.32	18	-0.22	2	20
mol:NO	0.017	0.034	-10000	0	-0.28	4	4
GNA15	0.013	0.07	-10000	0	-0.43	12	12
PGK/cGMP	0.007	0.069	-10000	0	-0.25	31	31
RhoA/GDP	0.025	0.006	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0.026	0.055	-10000	0	-0.29	2	2
NOS3	0.017	0.034	-10000	0	-0.28	4	4
RAC1	0.023	0.009	-10000	0	-10000	0	0
PRKCA	-0.061	0.18	0.31	9	-0.34	122	131
PRKCB	-0.075	0.18	0.35	5	-0.36	131	136
PRKCE	-0.066	0.18	0.32	8	-0.35	124	132
PRKCD	-0.077	0.2	0.32	7	-0.38	130	137
PRKCG	-0.086	0.19	0.36	7	-0.38	130	137
muscle contraction	-0.1	0.24	0.39	5	-0.48	131	136
PRKCZ	-0.07	0.17	0.33	7	-0.34	131	138
ARR3	-0.007	0.018	-10000	0	-0.13	1	1
TXA2/TP beta	0.01	0.052	-10000	0	-0.21	11	11
PRKCQ	-0.063	0.18	0.29	11	-0.35	122	133
MAPKKK cascade	-0.088	0.22	0.37	6	-0.44	128	134
SELE	-0.066	0.16	0.3	6	-0.32	132	138
TP beta/GNAI2/GDP/G beta/gamma	0.027	0.053	-10000	0	-0.21	9	9
ROCK1	0.026	0.004	-10000	0	-10000	0	0
GNA14	0.009	0.081	-10000	0	-0.34	23	23
chemotaxis	-0.13	0.29	0.39	5	-0.61	131	136
GNA12	0.022	0.009	-10000	0	-10000	0	0
GNA13	0.025	0.005	-10000	0	-10000	0	0
GNA11	0.017	0.06	-10000	0	-0.43	9	9
Rac1/GTP	0.016	0.007	-10000	0	-10000	0	0

×

Endothelins

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
AKT1	-0.056	0.13	0.24	1	-0.28	102	103
PTK2B	0.018	0.032	-10000	0	-0.13	22	22
mol:Ca2+	-0.045	0.22	-10000	0	-0.76	34	34
EDN1	-0.036	0.11	0.21	1	-0.3	47	48
EDN3	0.006	0.09	-10000	0	-0.4	23	23
EDN2	-0.006	0.031	-10000	0	-0.13	20	20
HRAS/GDP	-0.051	0.17	0.26	9	-0.44	47	56
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.033	0.13	-10000	0	-0.34	47	47
ADCY4	-0.069	0.14	-10000	0	-0.3	92	92
ADCY5	-0.073	0.14	-10000	0	-0.32	92	92
ADCY6	-0.067	0.13	-10000	0	-0.31	82	82
ADCY7	-0.067	0.13	-10000	0	-0.3	85	85
ADCY1	-0.072	0.14	-10000	0	-0.29	113	113
ADCY2	-0.071	0.14	-10000	0	-0.31	88	88
ADCY3	-0.067	0.13	-10000	0	-0.29	94	94
ADCY8	-0.081	0.15	-10000	0	-0.3	120	120
ADCY9	-0.067	0.14	-10000	0	-0.3	94	94
arachidonic acid secretion	-0.066	0.2	0.29	10	-0.46	78	88
ETB receptor/Endothelin-1/Gq/GTP	-0.026	0.12	-10000	0	-0.3	57	57
GNAO1	0.022	0.045	-10000	0	-0.43	5	5
HRAS	0.024	0.007	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	-0.013	0.13	-10000	0	-0.25	103	103
ETA receptor/Endothelin-1/Gs/GTP	-0.041	0.16	-10000	0	-0.26	155	155
mol:GTP	0	0.004	-10000	0	-10000	0	0
COL3A1	-0.099	0.2	0.23	1	-0.45	108	109
EDNRB	-0.014	0.12	-10000	0	-0.42	39	39
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.065	0.16	0.24	1	-0.38	66	67
CYSLTR1	-0.064	0.15	0.24	1	-0.42	48	49
SLC9A1	-0.034	0.098	0.17	1	-0.25	61	62
mol:GDP	-0.063	0.18	0.27	10	-0.47	50	60
SLC9A3	-0.074	0.25	-10000	0	-0.68	55	55
RAF1	-0.072	0.19	0.26	10	-0.45	72	82
JUN	-0.037	0.19	-10000	0	-0.62	32	32
JAK2	-0.055	0.13	0.24	1	-0.27	110	111
mol:IP3	-0.042	0.14	-10000	0	-0.41	40	40
ETA receptor/Endothelin-1	-0.04	0.17	0.41	1	-0.32	116	117
PLCB1	0.01	0.081	-10000	0	-0.43	17	17
PLCB2	0.011	0.073	-10000	0	-0.36	17	17
ETA receptor/Endothelin-3	-0.018	0.11	0.17	1	-0.3	48	49
FOS	-0.11	0.31	0.35	5	-0.87	65	70
Gai/GDP	0.002	0.14	-10000	0	-0.71	15	15
CRK	0.026	0.002	-10000	0	-10000	0	0
mol:Ca ++	-0.071	0.17	0.22	1	-0.43	62	63
BCAR1	0.025	0.02	-10000	0	-0.43	1	1
PRKCB1	-0.042	0.14	-10000	0	-0.4	40	40
GNAQ	0.024	0.011	-10000	0	-10000	0	0
GNAZ	0.026	0.004	-10000	0	-10000	0	0
GNAL	-0.028	0.15	-10000	0	-0.42	61	61
Gs family/GDP	-0.073	0.18	0.26	5	-0.42	67	72
ETA receptor/Endothelin-1/Gq/GTP	-0.029	0.12	0.19	1	-0.32	45	46
MAPK14	-0.033	0.12	-10000	0	-0.43	28	28
TRPC6	-0.049	0.24	-10000	0	-0.82	33	33
GNAI2	0.025	0.005	-10000	0	-10000	0	0
GNAI3	0.021	0.01	-10000	0	-10000	0	0
GNAI1	0.019	0.036	-10000	0	-0.43	3	3
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.032	0.13	-10000	0	-0.39	37	37
ETB receptor/Endothelin-2	-0.004	0.09	-10000	0	-0.3	37	37
ETB receptor/Endothelin-3	-0.003	0.11	-10000	0	-0.34	49	49
ETB receptor/Endothelin-1	-0.027	0.13	-10000	0	-0.31	69	69
MAPK3	-0.1	0.27	0.33	8	-0.76	65	73
MAPK1	-0.1	0.28	0.33	8	-0.75	66	74
Rac1/GDP	-0.052	0.16	0.28	2	-0.45	43	45
cAMP biosynthetic process	-0.073	0.16	0.22	1	-0.37	79	80
MAPK8	-0.049	0.22	-10000	0	-0.67	40	40
SRC	0.025	0.005	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.022	0.098	0.16	1	-0.3	38	39
p130Cas/CRK/Src/PYK2	-0.049	0.18	0.32	10	-0.53	37	47
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.053	0.16	0.34	1	-0.45	44	45
COL1A2	-0.058	0.16	-10000	0	-0.46	43	43
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.018	0.089	-10000	0	-0.26	35	35
mol:DAG	-0.042	0.14	-10000	0	-0.41	40	40
MAP2K2	-0.081	0.22	0.33	15	-0.57	69	84
MAP2K1	-0.089	0.23	0.27	7	-0.59	69	76
EDNRA	-0.033	0.12	0.21	1	-0.32	42	43
positive regulation of muscle contraction	-0.024	0.13	0.21	38	-0.3	44	82
Gq family/GDP	-0.043	0.17	-10000	0	-0.48	40	40
HRAS/GTP	-0.061	0.17	0.25	11	-0.44	52	63
PRKCH	-0.042	0.13	-10000	0	-0.43	33	33
RAC1	0.023	0.009	-10000	0	-10000	0	0
PRKCA	-0.039	0.14	0.23	8	-0.44	33	41
PRKCB	-0.052	0.14	-10000	0	-0.44	37	37
PRKCE	-0.043	0.14	0.22	1	-0.43	33	34
PRKCD	-0.052	0.15	-10000	0	-0.44	45	45
PRKCG	-0.075	0.15	-10000	0	-0.39	61	61
regulation of vascular smooth muscle contraction	-0.13	0.36	0.39	5	-1	64	69
PRKCQ	-0.035	0.15	0.22	21	-0.46	33	54
PLA2G4A	-0.073	0.22	0.29	10	-0.5	78	88
GNA14	0.008	0.081	-10000	0	-0.34	23	23
GNA15	0.012	0.071	-10000	0	-0.36	16	16
GNA12	0.022	0.009	-10000	0	-10000	0	0
GNA11	0.016	0.06	-10000	0	-0.43	9	9
Rac1/GTP	-0.012	0.13	-10000	0	-0.25	102	102
MMP1	0.017	0.1	0.42	12	-0.83	1	13

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.044	0.19	-10000	0	-0.58	53	53
IHH	0.012	0.056	0.18	1	-0.19	8	9
SHH Np/Cholesterol/GAS1	-0.011	0.084	0.16	12	-0.24	53	65
LRPAP1	0.026	0.005	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.011	0.083	0.24	53	-0.15	12	65
SMO/beta Arrestin2	-0.005	0.12	-10000	0	-0.39	20	20
SMO	-0.02	0.11	-10000	0	-0.37	33	33
AKT1	-0.003	0.11	-10000	0	-0.53	13	13
ARRB2	0.026	0.002	-10000	0	-10000	0	0
BOC	0.023	0.036	-10000	0	-0.43	3	3
ADRBK1	0.025	0.005	-10000	0	-10000	0	0
heart looping	-0.019	0.11	-10000	0	-0.36	33	33
STIL	-0.012	0.13	0.23	3	-0.28	56	59
DHH N/PTCH2	0.004	0.085	-10000	0	-0.31	31	31
DHH N/PTCH1	-0.02	0.12	-10000	0	-0.28	79	79
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
DHH	-0.007	0.1	-10000	0	-0.43	27	27
PTHLH	-0.061	0.26	-10000	0	-0.78	53	53
determination of left/right symmetry	-0.019	0.11	-10000	0	-0.36	33	33
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
skeletal system development	-0.06	0.25	-10000	0	-0.77	53	53
IHH N/Hhip	-0.04	0.14	-10000	0	-0.33	78	78
DHH N/Hhip	-0.049	0.14	-10000	0	-0.31	101	101
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.019	0.11	-10000	0	-0.36	33	33
pancreas development	-0.058	0.16	-10000	0	-0.29	135	135
HHAT	0.012	0.077	-10000	0	-0.43	15	15
PI3K	0.038	0.007	-10000	0	-10000	0	0
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	0.016	0.047	-10000	0	-0.43	3	3
somite specification	-0.019	0.11	-10000	0	-0.36	33	33
SHH Np/Cholesterol/PTCH1	-0.036	0.11	-10000	0	-0.28	68	68
SHH Np/Cholesterol/PTCH2	-0.016	0.082	0.15	2	-0.24	56	58
SHH Np/Cholesterol/Megalin	-0.059	0.12	0.15	8	-0.27	115	123
SHH	-0.03	0.097	-10000	0	-0.31	52	52
catabolic process	-0.018	0.12	-10000	0	-0.34	52	52
SMO/Vitamin D3	-0.032	0.12	0.29	2	-0.32	39	41
SHH Np/Cholesterol/Hhip	-0.048	0.12	0.16	8	-0.27	98	106
LRP2	-0.093	0.18	-10000	0	-0.31	183	183
receptor-mediated endocytosis	-0.066	0.14	-10000	0	-0.4	47	47
SHH Np/Cholesterol/BOC	-0.014	0.08	-10000	0	-0.24	54	54
SHH Np/Cholesterol/CDO	-0.02	0.089	0.17	1	-0.25	59	60
mesenchymal cell differentiation	0.048	0.12	0.27	98	-0.15	8	106
mol:Vitamin D3	-0.001	0.14	0.32	3	-0.28	68	71
IHH N/PTCH2	0.023	0.051	-10000	0	-0.33	6	6
CDON	0.001	0.095	-10000	0	-0.43	23	23
IHH N/PTCH1	-0.011	0.12	-10000	0	-0.34	52	52
Megalin/LRPAP1	-0.052	0.14	-10000	0	-0.3	108	108
PTCH2	0.016	0.048	-10000	0	-0.28	10	10
SHH Np/Cholesterol	-0.019	0.075	0.2	1	-0.23	52	53
PTCH1	-0.019	0.12	-10000	0	-0.34	52	52
HHIP	-0.058	0.16	-10000	0	-0.29	135	135

×

Effects of Botulinum toxin

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
STX1A	-0.011	0.046	-10000	0	-0.1	77	77
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	-0.019	0.12	-10000	0	-0.31	69	69
STXBP1	0.016	0.044	-10000	0	-0.16	26	26
ACh/CHRNA1	-0.042	0.11	0.13	8	-0.25	84	92
RAB3GAP2/RIMS1/UNC13B	0.01	0.11	-10000	0	-0.26	67	67
mol:Ca2+	0	0	-10000	0	-10000	0	0
UniProt:P30996	0	0	-10000	0	-10000	0	0
UniProt:Q60393	0	0	-10000	0	-10000	0	0
CST086	0	0	-10000	0	-10000	0	0
RIMS1	-0.049	0.16	-10000	0	-0.32	112	112
mol:ACh	-0.008	0.057	0.098	60	-0.11	74	134
RAB3GAP2	0.026	0.004	-10000	0	-10000	0	0
STX1A/SNAP25/VAMP2	-0.031	0.12	-10000	0	-0.25	92	92
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	-0.042	0.11	0.13	8	-0.25	84	92
UNC13B	0.025	0.021	-10000	0	-0.43	1	1
CHRNA1	-0.065	0.15	-10000	0	-0.43	68	68
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	-0.056	0.13	0.13	2	-0.31	90	92
SNAP25	-0.043	0.098	-10000	0	-0.26	86	86
VAMP2	0.005	0	-10000	0	-10000	0	0
SYT1	-0.088	0.17	-10000	0	-0.43	92	92
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0	0.052	-10000	0	-0.16	32	32
STX1A/SNAP25 fragment 1/VAMP2	-0.031	0.12	-10000	0	-0.25	92	92

×

Syndecan-4-mediated signaling events

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
PTK2	0.013	0.069	0.25	1	-0.43	5	6
Syndecan-4/Syndesmos	-0.059	0.2	0.32	1	-0.46	92	93
positive regulation of JNK cascade	-0.053	0.2	0.31	1	-0.44	93	94
Syndecan-4/ADAM12	-0.068	0.2	0.34	1	-0.46	93	94
CCL5	-0.025	0.12	-10000	0	-0.43	39	39
Rac1/GDP	0.017	0.007	-10000	0	-10000	0	0
DNM2	0.025	0.006	-10000	0	-10000	0	0
ITGA5	0.017	0.043	-10000	0	-0.16	24	24
SDCBP	0.025	0.006	-10000	0	-10000	0	0
PLG	0.001	0.026	-10000	0	-0.17	1	1
ADAM12	-0.001	0.077	-10000	0	-0.18	65	65
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0.026	0.003	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.033	0.02	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	-0.079	0.22	0.32	1	-0.49	95	96
Syndecan-4/CXCL12/CXCR4	-0.056	0.21	0.32	1	-0.46	93	94
Syndecan-4/Laminin alpha3	-0.07	0.21	0.32	1	-0.48	94	95
MDK	-0.002	0.097	-10000	0	-0.27	48	48
Syndecan-4/FZD7	-0.078	0.22	-10000	0	-0.5	96	96
Syndecan-4/Midkine	-0.067	0.21	0.32	1	-0.47	90	91
FZD7	-0.018	0.13	-10000	0	-0.43	48	48
Syndecan-4/FGFR1/FGF	-0.044	0.19	0.3	1	-0.44	85	86
THBS1	-0.018	0.1	-10000	0	-0.43	23	23
integrin-mediated signaling pathway	-0.066	0.2	0.32	1	-0.46	92	93
positive regulation of MAPKKK cascade	-0.053	0.2	0.31	1	-0.44	93	94
Syndecan-4/TACI	-0.063	0.2	0.31	1	-0.46	93	94
CXCR4	0.012	0.072	-10000	0	-0.27	25	25
cell adhesion	0.017	0.036	0.2	14	-0.2	1	15
Syndecan-4/Dynamin	-0.063	0.2	-10000	0	-0.46	93	93
Syndecan-4/TSP1	-0.071	0.21	0.32	1	-0.48	94	95
Syndecan-4/GIPC	-0.063	0.2	-10000	0	-0.46	92	92
Syndecan-4/RANTES	-0.077	0.21	0.32	1	-0.48	94	95
ITGB1	0.023	0.012	-10000	0	-10000	0	0
LAMA1	-0.024	0.14	-10000	0	-0.43	51	51
LAMA3	-0.004	0.1	-10000	0	-0.29	49	49
RAC1	0.023	0.009	-10000	0	-10000	0	0
PRKCA	0.035	0.16	0.85	18	-0.4	1	19
Syndecan-4/alpha-Actinin	-0.061	0.2	0.32	1	-0.46	93	94
TFPI	-0.024	0.12	-10000	0	-0.23	99	99
F2	0.006	0.031	-10000	0	-0.14	1	1
alpha5/beta1 Integrin	0.029	0.034	-10000	0	-0.26	3	3
positive regulation of cell adhesion	-0.094	0.22	0.31	1	-0.49	103	104
ACTN1	0.014	0.044	-10000	0	-0.14	35	35
TNC	-0.005	0.1	-10000	0	-0.43	24	24
Syndecan-4/CXCL12	-0.062	0.2	0.32	1	-0.46	93	94
FGF6	-0.013	0.01	-10000	0	-10000	0	0
RHOA	0.026	0.004	-10000	0	-10000	0	0
CXCL12	0.021	0.038	-10000	0	-0.24	8	8
TNFRSF13B	-0.003	0.028	-10000	0	-0.13	11	11
FGF2	0.024	0.029	-10000	0	-0.43	2	2
FGFR1	0.025	0.005	-10000	0	-10000	0	0
Syndecan-4/PI-4-5-P2	-0.079	0.19	-10000	0	-0.46	93	93
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.019	0.034	-10000	0	-0.16	5	5
cell migration	-0.013	0.015	-10000	0	-10000	0	0
PRKCD	0.001	0.096	-10000	0	-0.41	26	26
vasculogenesis	-0.068	0.2	0.32	1	-0.46	94	95
SDC4	-0.077	0.2	-10000	0	-0.48	93	93
Syndecan-4/Tenascin C	-0.069	0.21	0.32	1	-0.48	92	93
Syndecan-4/PI-4-5-P2/PKC alpha	-0.027	0.016	-10000	0	-10000	0	0
Syndecan-4/Syntenin	-0.058	0.2	0.32	1	-0.46	89	90
MMP9	-0.045	0.13	-10000	0	-0.23	133	133
Rac1/GTP	0.017	0.036	0.2	14	-0.2	1	15
cytoskeleton organization	-0.056	0.2	0.32	1	-0.44	92	93
GIPC1	0.025	0.009	-10000	0	-0.13	1	1
Syndecan-4/TFPI	-0.074	0.21	0.34	1	-0.48	93	94

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.015	0.07	-10000	0	-0.3	22	22
VLDLR	0.014	0.067	-10000	0	-0.35	15	15
CRKL	0.026	0.008	-10000	0	-0.13	1	1
LRPAP1	0.026	0.005	-10000	0	-10000	0	0
FYN	0.025	0.005	-10000	0	-10000	0	0
ITGA3	0.017	0.046	-10000	0	-0.43	3	3
RELN/VLDLR/Fyn	0	0.1	-10000	0	-0.26	67	67
MAPK8IP1/MKK7/MAP3K11/JNK1	0.059	0.055	-10000	0	-0.22	15	15
AKT1	-0.047	0.11	-10000	0	-0.26	98	98
MAP2K7	0.025	0.005	-10000	0	-10000	0	0
RAPGEF1	0.025	0.005	-10000	0	-10000	0	0
DAB1	-0.039	0.15	-10000	0	-0.36	80	80
RELN/LRP8/DAB1	-0.024	0.12	-10000	0	-0.24	103	103
LRPAP1/LRP8	0.03	0.026	-10000	0	-0.3	2	2
RELN/LRP8/DAB1/Fyn	-0.017	0.11	-10000	0	-0.23	96	96
DAB1/alpha3/beta1 Integrin	-0.021	0.11	-10000	0	-0.24	78	78
long-term memory	-0.1	0.17	-10000	0	-0.32	154	154
DAB1/LIS1	-0.014	0.12	-10000	0	-0.23	98	98
DAB1/CRLK/C3G	-0.02	0.11	-10000	0	-0.24	81	81
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
DAB1/NCK2	-0.014	0.12	-10000	0	-0.23	97	97
ARHGEF2	0.025	0.02	-10000	0	-0.43	1	1
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	-0.071	0.17	-10000	0	-0.29	155	155
CDK5R1	0	0.1	-10000	0	-0.42	30	30
RELN	-0.046	0.14	-10000	0	-0.43	58	58
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
RELN/LRP8/Fyn	0.001	0.095	-10000	0	-0.25	58	58
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.052	0.16	-10000	0	-0.28	134	134
MAPK8	0.014	0.071	-10000	0	-0.43	13	13
RELN/VLDLR/DAB1	-0.031	0.12	-10000	0	-0.25	103	103
ITGB1	0.023	0.012	-10000	0	-10000	0	0
MAP1B	-0.032	0.12	0.16	5	-0.25	100	105
RELN/LRP8	0.003	0.095	-10000	0	-0.25	57	57
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.057	0.15	-10000	0	-0.28	140	140
PI3K	0.038	0.007	-10000	0	-10000	0	0
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.028	0.037	-10000	0	-0.27	4	4
RAP1A	-0.022	0.12	0.31	9	-0.35	14	23
PAFAH1B1	0.026	0.002	-10000	0	-10000	0	0
MAPK8IP1	0.022	0.04	-10000	0	-0.43	4	4
CRLK/C3G	0.037	0.01	-10000	0	-10000	0	0
GRIN2B	-0.077	0.16	-10000	0	-0.43	83	83
NCK2	0.026	0.002	-10000	0	-10000	0	0
neuron differentiation	-0.028	0.13	-10000	0	-0.36	45	45
neuron adhesion	-0.014	0.13	0.34	12	-0.37	10	22
LRP8	0.02	0.03	-10000	0	-0.43	2	2
GSK3B	-0.052	0.11	-10000	0	-0.25	91	91
RELN/VLDLR/DAB1/Fyn	-0.024	0.12	-10000	0	-0.24	102	102
MAP3K11	0.025	0.005	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.049	0.12	-10000	0	-0.27	103	103
CDK5	0.02	0.011	-10000	0	-10000	0	0
MAPT	0.006	0.098	0.77	6	-0.39	8	14
neuron migration	-0.042	0.16	0.23	54	-0.31	94	148
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.029	0.13	-10000	0	-0.36	45	45
RELN/VLDLR	0.005	0.097	-10000	0	-0.23	66	66

×

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	0.003	0.078	-10000	0	-0.31	25	25
CDKN2C	0.01	0.041	-10000	0	-0.15	10	10
CDKN2A	-0.013	0.1	-10000	0	-0.28	55	55
CCND2	0.016	0.068	0.21	47	-0.19	1	48
RB1	-0.023	0.079	0.12	1	-0.24	51	52
CDK4	0.021	0.077	0.24	48	-0.17	1	49
CDK6	0.017	0.081	0.25	44	-0.16	10	54
G1/S progression	0.042	0.099	0.26	75	-0.25	3	78

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	-0.007	0.006	-10000	0	-10000	0	0
RAS family/GTP	-0.035	0.12	-10000	0	-0.3	51	51
NFATC4	-0.057	0.089	0.22	2	-0.23	49	51
ERBB2IP	0.026	0.02	-10000	0	-0.42	1	1
HSP90 (dimer)	0.025	0.005	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.047	0.11	0.2	1	-0.24	115	116
JUN	-0.022	0.083	0.2	3	-0.38	9	12
HRAS	0.024	0.006	-10000	0	-10000	0	0
DOCK7	-0.064	0.098	-10000	0	-0.24	111	111
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.034	0.13	-10000	0	-0.25	119	119
AKT1	0.003	0.007	-10000	0	-10000	0	0
BAD	-0.006	0.004	-10000	0	-10000	0	0
MAPK10	-0.03	0.065	0.17	2	-0.22	7	9
mol:GTP	-0.001	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.05	0.12	0.21	1	-0.26	115	116
RAF1	-0.044	0.12	0.27	6	-0.32	45	51
ErbB2/ErbB3/neuregulin 2	-0.003	0.08	0.16	2	-0.25	40	42
STAT3	0.028	0.043	-10000	0	-0.91	1	1
cell migration	-0.022	0.077	0.22	13	-0.2	11	24
mol:PI-3-4-5-P3	-0.002	0.002	-10000	0	-10000	0	0
cell proliferation	-0.1	0.25	0.35	2	-0.61	82	84
FOS	-0.083	0.2	0.28	3	-0.41	118	121
NRAS	0.021	0.01	-10000	0	-10000	0	0
mol:Ca2+	-0.047	0.11	0.2	1	-0.24	115	116
MAPK3	-0.08	0.21	0.36	2	-0.51	70	72
MAPK1	-0.083	0.21	0.36	2	-0.51	70	72
JAK2	-0.067	0.097	-10000	0	-0.24	108	108
NF2	0.005	0.033	-10000	0	-0.69	1	1
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.052	0.12	0.18	1	-0.26	116	117
NRG1	-0.081	0.18	-10000	0	-0.32	156	156
GRB2/SOS1	0.037	0.009	-10000	0	-10000	0	0
MAPK8	-0.053	0.12	-10000	0	-0.26	113	113
MAPK9	-0.029	0.063	0.17	3	-0.21	5	8
ERBB2	-0.022	0.017	-10000	0	-0.32	1	1
ERBB3	-0.017	0.12	-10000	0	-0.35	57	57
SHC1	0.024	0.014	-10000	0	-10000	0	0
RAC1	0.023	0.009	-10000	0	-10000	0	0
apoptosis	0.003	0.013	-10000	0	-0.2	1	1
STAT3 (dimer)	0.029	0.042	-10000	0	-0.89	1	1
RNF41	-0.01	0.008	-10000	0	-10000	0	0
FRAP1	-0.004	0.003	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.041	0.074	-10000	0	-0.18	96	96
ErbB2/ErbB2/HSP90 (dimer)	0	0.025	-10000	0	-0.27	1	1
CHRNA1	-0.091	0.24	0.33	2	-0.63	71	73
myelination	-0.054	0.089	0.23	3	-0.26	22	25
PPP3CB	-0.065	0.091	-10000	0	-0.22	111	111
KRAS	0.025	0.005	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.026	0.11	-10000	0	-0.23	100	100
NRG2	0.025	0.02	-10000	0	-0.43	1	1
mol:GDP	-0.053	0.12	0.18	1	-0.26	117	118
SOS1	0.026	0.002	-10000	0	-10000	0	0
MAP2K2	-0.048	0.13	0.27	6	-0.34	42	48
SRC	0.025	0.005	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.001	-10000	0	-10000	0	0
PTPN11	-0.068	0.097	-10000	0	-0.24	114	114
MAP2K1	-0.088	0.2	-10000	0	-0.58	38	38
heart morphogenesis	-0.047	0.11	0.2	1	-0.24	115	116
RAS family/GDP	-0.026	0.12	0.23	1	-0.29	48	49
GRB2	0.025	0.006	-10000	0	-10000	0	0
PRKACA	0.008	0.035	-10000	0	-0.74	1	1
CHRNE	-0.002	0.031	0.1	1	-0.18	9	10
HSP90AA1	0.025	0.005	-10000	0	-10000	0	0
activation of caspase activity	-0.003	0.007	-10000	0	-10000	0	0
nervous system development	-0.047	0.11	0.2	1	-0.24	115	116
CDC42	0.022	0.01	-10000	0	-10000	0	0

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.13	0.3	-10000	0	-0.84	50	50
PCK1	-0.18	0.39	-10000	0	-1.2	50	50
HNF4A	-0.15	0.33	-10000	0	-0.92	53	53
KCNJ11	-0.18	0.4	-10000	0	-1	76	76
AKT1	-0.067	0.18	-10000	0	-0.43	47	47
response to starvation	-0.003	0.026	-10000	0	-0.22	4	4
DLK1	-0.16	0.35	-10000	0	-0.89	71	71
NKX2-1	-0.058	0.15	0.3	3	-0.37	47	50
ACADM	-0.13	0.3	-10000	0	-0.83	51	51
TAT	-0.19	0.39	-10000	0	-1.1	55	55
CEBPB	0.013	0.073	-10000	0	-0.36	17	17
CEBPA	0.015	0.05	-10000	0	-0.43	5	5
TTR	-0.12	0.27	0.53	3	-0.84	38	41
PKLR	-0.13	0.3	-10000	0	-0.8	58	58
APOA1	-0.18	0.4	-10000	0	-1.1	56	56
CPT1C	-0.13	0.3	-10000	0	-0.84	49	49
ALAS1	-0.06	0.18	0.46	1	-0.71	4	5
TFRC	-0.14	0.3	-10000	0	-0.93	38	38
FOXF1	0.019	0.042	-10000	0	-0.19	16	16
NF1	0.03	0.02	-10000	0	-0.42	1	1
HNF1A (dimer)	0.025	0.026	-10000	0	-0.44	1	1
CPT1A	-0.13	0.3	-10000	0	-0.82	55	55
HMGCS1	-0.13	0.3	-10000	0	-0.82	56	56
NR3C1	-0.017	0.089	-10000	0	-0.2	85	85
CPT1B	-0.15	0.32	-10000	0	-0.84	64	64
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.024	0.013	-10000	0	-10000	0	0
GCK	-0.16	0.37	0.5	1	-0.9	78	79
CREB1	0.008	0.058	-10000	0	-0.18	36	36
IGFBP1	-0.22	0.48	-10000	0	-1.2	85	85
PDX1	-0.058	0.17	-10000	0	-0.57	10	10
UCP2	-0.14	0.32	-10000	0	-0.84	61	61
ALDOB	-0.14	0.35	-10000	0	-0.92	56	56
AFP	-0.035	0.1	-10000	0	-0.36	22	22
BDH1	-0.16	0.35	-10000	0	-0.95	62	62
HADH	-0.13	0.32	-10000	0	-0.85	56	56
F2	-0.15	0.35	-10000	0	-0.99	45	45
HNF1A	0.025	0.026	-10000	0	-0.44	1	1
G6PC	-0.034	0.16	-10000	0	-0.88	10	10
SLC2A2	-0.064	0.19	-10000	0	-0.54	16	16
INS	0.008	0.086	0.21	59	-0.4	4	63
FOXA1	-0.007	0.087	-10000	0	-0.28	32	32
FOXA3	-0.041	0.14	-10000	0	-0.37	61	61
FOXA2	-0.15	0.37	-10000	0	-0.92	64	64
ABCC8	-0.19	0.41	-10000	0	-0.97	88	88
ALB	-0.07	0.23	-10000	0	-0.91	32	32

×

Syndecan-3-mediated 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
CTTN	0.025	0.005	-10000	0	-10000	0	0
Syndecan-3/Src/Cortactin	-0.012	0.14	-10000	0	-0.35	64	64
Syndecan-3/Neurocan	-0.042	0.15	-10000	0	-0.37	77	77
POMC	0.015	0.063	-10000	0	-0.28	18	18
EGFR	-0.016	0.12	-10000	0	-0.4	46	46
Syndecan-3/EGFR	-0.051	0.15	-10000	0	-0.38	74	74
AGRP	0.012	0.024	-10000	0	-10000	0	0
NCSTN	0.026	0.004	-10000	0	-10000	0	0
PSENEN	0.022	0.01	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
APH1B	0.026	0.003	-10000	0	-10000	0	0
APH1A	0.026	0.004	-10000	0	-10000	0	0
NCAN	-0.001	0.1	-10000	0	-0.4	31	31
long-term memory	-0.013	0.14	-10000	0	-0.35	72	72
Syndecan-3/IL8	-0.054	0.16	-10000	0	-0.4	77	77
PSEN1	0.025	0.005	-10000	0	-10000	0	0
Src/Cortactin	0.036	0.011	-10000	0	-10000	0	0
FYN	0.025	0.005	-10000	0	-10000	0	0
limb bud formation	-0.046	0.14	-10000	0	-0.38	77	77
MC4R	-0.051	0.16	-10000	0	-0.43	70	70
SRC	0.025	0.005	-10000	0	-10000	0	0
PTN	0.019	0.03	-10000	0	-0.43	2	2
FGFR/FGF/Syndecan-3	-0.046	0.14	-10000	0	-0.38	77	77
neuron projection morphogenesis	-0.015	0.15	0.26	1	-0.35	65	66
Syndecan-3/AgRP	-0.03	0.14	-10000	0	-0.37	77	77
Syndecan-3/AgRP/MC4R	-0.045	0.16	-10000	0	-0.38	77	77
Fyn/Cortactin	0.036	0.01	-10000	0	-10000	0	0
SDC3	-0.047	0.14	-10000	0	-0.39	77	77
GO:0007205	0	0	-10000	0	-10000	0	0
positive regulation of leukocyte migration	-0.053	0.16	-10000	0	-0.39	77	77
IL8	-0.061	0.15	-10000	0	-0.25	158	158
Syndecan-3/Fyn/Cortactin	-0.013	0.14	-10000	0	-0.36	72	72
Syndecan-3/CASK	-0.045	0.14	-10000	0	-0.36	77	77
alpha-MSH/MC4R	-0.025	0.13	-10000	0	-0.32	76	76
Gamma Secretase	0.063	0.032	-10000	0	-10000	0	0

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.024	0.036	-10000	0	-0.26	6	6
ARNO/beta Arrestin1-2	-0.099	0.31	-10000	0	-0.8	82	82
EGFR	-0.016	0.12	-10000	0	-0.4	46	46
EPHA2	0.012	0.045	-10000	0	-0.15	29	29
USP6	0.023	0.022	-10000	0	-10000	0	0
IQSEC1	0.023	0.027	-10000	0	-0.17	8	8
EGFR/EGFR/EGF/EGF	-0.02	0.12	-10000	0	-0.32	69	69
ARRB2	0.011	0.007	-10000	0	-10000	0	0
mol:GTP	0.007	0.042	0.18	5	-0.17	11	16
ARRB1	0.012	0.077	-10000	0	-0.43	15	15
FBXO8	0.025	0.005	-10000	0	-10000	0	0
TSHR	-0.084	0.17	-10000	0	-0.28	187	187
EGF	-0.01	0.11	-10000	0	-0.43	33	33
somatostatin receptor activity	0	0	0.001	59	-0.001	26	85
ARAP2	0.012	0.079	-10000	0	-0.43	16	16
mol:GDP	-0.016	0.13	0.19	45	-0.29	45	90
mol:PI-3-4-5-P3	0	0	0.001	78	-0.001	12	90
ITGA2B	-0.012	0.12	-10000	0	-0.43	40	40
ARF6	0.026	0.004	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.054	0.036	-10000	0	-0.25	3	3
ADAP1	0.014	0.054	-10000	0	-0.24	17	17
KIF13B	0.025	0.005	-10000	0	-10000	0	0
HGF/MET	-0.04	0.12	-10000	0	-0.28	83	83
PXN	0.026	0.004	-10000	0	-10000	0	0
ARF6/GTP	0.002	0.13	0.25	53	-0.26	32	85
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.004	0.11	-10000	0	-0.28	70	70
ADRB2	0.005	0.094	-10000	0	-0.42	24	24
receptor agonist activity	0	0	0	28	0	23	51
actin filament binding	0	0	0.001	60	0	28	88
SRC	0.025	0.005	-10000	0	-10000	0	0
ITGB3	-0.001	0.082	-10000	0	-0.19	64	64
GNAQ	0.026	0.004	-10000	0	-10000	0	0
EFA6/PI-4-5-P2	0	0.001	0.002	72	-0.001	17	89
ARF6/GDP	-0.026	0.14	0.23	5	-0.42	36	41
ARF6/GDP/GULP/ACAP1	-0.012	0.16	0.22	31	-0.34	52	83
alphaIIb/beta3 Integrin/paxillin/GIT1	0.036	0.094	-10000	0	-0.24	51	51
ACAP1	0.01	0.06	-10000	0	-0.43	5	5
ACAP2	0.026	0.004	-10000	0	-10000	0	0
LHCGR/beta Arrestin2	0.023	0.007	-10000	0	-10000	0	0
EFNA1	0.024	0.014	-10000	0	-0.13	4	4
HGF	-0.009	0.091	-10000	0	-0.2	69	69
CYTH3	0.006	0.002	-10000	0	-10000	0	0
CYTH2	-0.14	0.38	-10000	0	-1	81	81
NCK1	0.025	0.02	-10000	0	-0.43	1	1
fibronectin binding	0	0	0.001	64	0	25	89
endosomal lumen acidification	0	0	0.001	61	0	31	92
microtubule-based process	0	0	-10000	0	0	12	12
GULP1	-0.016	0.13	-10000	0	-0.37	55	55
GNAQ/ARNO	-0.12	0.35	-10000	0	-0.93	81	81
mol:Phosphatidic acid	0	0	0	18	-10000	0	18
PIP3-E	0	0	0	39	0	14	53
MET	-0.047	0.14	-10000	0	-0.43	52	52
GNA14	0.009	0.081	-10000	0	-0.34	23	23
GNA15	0.013	0.07	-10000	0	-0.43	12	12
GIT1	0.026	0.002	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0.001	0.001	64	-0.001	20	84
GNA11	0.017	0.06	-10000	0	-0.43	9	9
LHCGR	0.009	0.031	-10000	0	-0.13	16	16
AGTR1	0.001	0.093	-10000	0	-0.29	39	39
desensitization of G-protein coupled receptor protein signaling pathway	0.023	0.007	-10000	0	-10000	0	0
IPCEF1/ARNO	-0.13	0.33	-10000	0	-0.88	81	81
alphaIIb/beta3 Integrin	-0.01	0.11	-10000	0	-0.31	53	53

×

Aurora C 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
INCENP	0.025	0.021	-9999	-0.43	1	1
Aurora C/Aurora B/INCENP	-0.011	0.11	-9999	-0.23	94	94
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.007	0.031	-9999	-10000	0	0
AURKB	-0.072	0.17	-9999	-0.3	152	152
AURKC	0.011	0.051	-9999	-0.18	26	26

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.24	0.36	-10000	0	-1.1	39	39
STAT6 (cleaved dimer)	-0.28	0.39	-10000	0	-1	75	75
IGHG1	-0.1	0.2	-10000	0	-0.98	13	13
IGHG3	-0.24	0.34	-10000	0	-0.95	56	56
AKT1	-0.18	0.31	-10000	0	-0.89	58	58
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.16	0.31	-10000	0	-0.94	49	49
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.2	0.33	-10000	0	-0.94	61	61
THY1	-0.26	0.39	-10000	0	-1.2	41	41
MYB	-0.016	0.12	-10000	0	-0.28	67	67
HMGA1	0.025	0.01	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.21	0.31	-10000	0	-0.81	75	75
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.2	0.33	-10000	0	-0.94	63	63
SP1	0.025	0.019	-10000	0	-0.12	1	1
INPP5D	0.022	0.037	-10000	0	-0.28	6	6
SOCS5	0.033	0.02	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.27	0.38	-10000	0	-1	66	66
SOCS1	-0.21	0.28	-10000	0	-0.73	59	59
SOCS3	-0.23	0.36	-10000	0	-1	63	63
FCER2	-0.26	0.4	-10000	0	-1.1	54	54
PARP14	0.017	0.046	-10000	0	-0.22	13	13
CCL17	-0.25	0.36	-10000	0	-1.1	39	39
GRB2	0.025	0.006	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.14	0.24	-10000	0	-0.7	49	49
T cell proliferation	-0.27	0.38	-10000	0	-1.1	60	60
IL4R/JAK1	-0.25	0.36	-10000	0	-1.1	40	40
EGR2	-0.34	0.5	-10000	0	-1.3	76	76
JAK2	-0.008	0.041	-10000	0	-10000	0	0
JAK3	-0.011	0.1	-10000	0	-0.26	55	55
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
JAK1	0.008	0.022	-10000	0	-10000	0	0
COL1A2	-0.088	0.2	-10000	0	-1.3	7	7
CCL26	-0.22	0.37	-10000	0	-1	42	42
IL4R	-0.26	0.38	-10000	0	-1.1	39	39
PTPN6	0.019	0.065	-10000	0	-0.42	10	10
IL13RA2	-0.42	0.55	-10000	0	-1.3	124	124
IL13RA1	-0.013	0.071	-10000	0	-0.42	9	9
IRF4	-0.12	0.32	-10000	0	-1.3	30	30
ARG1	-0.09	0.21	-10000	0	-1	16	16
CBL	-0.19	0.29	-10000	0	-0.76	71	71
GTF3A	0.003	0.052	-10000	0	-0.15	26	26
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
IL13RA1/JAK2	-0.01	0.07	-10000	0	-0.32	8	8
IRF4/BCL6	-0.099	0.3	-10000	0	-1.2	30	30
CD40LG	0.003	0.054	-10000	0	-10000	0	0
MAPK14	-0.22	0.32	-10000	0	-0.83	76	76
mitosis	-0.17	0.29	-10000	0	-0.82	58	58
STAT6	-0.28	0.4	-10000	0	-1.1	53	53
SPI1	0.015	0.064	-10000	0	-0.4	10	10
RPS6KB1	-0.16	0.28	-10000	0	-0.78	58	58
STAT6 (dimer)	-0.28	0.4	-10000	0	-1.1	53	53
STAT6 (dimer)/PARP14	-0.26	0.38	-10000	0	-1.1	56	56
mast cell activation	0.007	0.011	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.18	0.31	-10000	0	-0.86	60	60
FRAP1	-0.18	0.31	-10000	0	-0.89	58	58
LTA	-0.28	0.42	-10000	0	-1.3	53	53
FES	0.024	0.024	-10000	0	-0.21	4	4
T-helper 1 cell differentiation	0.27	0.39	1.1	53	-10000	0	53
CCL11	-0.25	0.34	-10000	0	-1	39	39
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.17	0.3	-10000	0	-0.86	53	53
IL2RG	-0.002	0.087	-10000	0	-0.22	50	50
IL10	-0.33	0.5	-10000	0	-1.3	81	81
IRS1	0.026	0.003	-10000	0	-10000	0	0
IRS2	0.024	0.021	-10000	0	-0.43	1	1
IL4	-0.064	0.12	-10000	0	-0.88	4	4
IL5	-0.25	0.36	-10000	0	-1.1	35	35
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.22	0.32	-10000	0	-0.92	43	43
COL1A1	-0.26	0.49	-10000	0	-1.4	77	77
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.25	0.36	-10000	0	-1.1	36	36
IL2R gamma/JAK3	-0.009	0.1	-10000	0	-0.27	53	53
TFF3	-0.25	0.36	-10000	0	-1.1	36	36
ALOX15	-0.26	0.36	-10000	0	-1.1	37	37
MYBL1	0.024	0.011	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.24	0.35	-10000	0	-0.92	68	68
SHC1	0.024	0.014	-10000	0	-10000	0	0
CEBPB	0.013	0.074	-10000	0	-0.34	19	19
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.19	0.33	-10000	0	-0.93	62	62
mol:PI-3-4-5-P3	-0.18	0.31	-10000	0	-0.89	58	58
PI3K	-0.19	0.34	-10000	0	-0.98	58	58
DOK2	-0.016	0.11	-10000	0	-0.25	77	77
ETS1	0.022	0.052	-10000	0	-0.37	7	7
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.13	0.23	-10000	0	-0.67	47	47
ITGB3	-0.27	0.39	-10000	0	-1.2	49	49
PIGR	-0.34	0.51	-10000	0	-1.3	81	81
IGHE	0.011	0.058	0.15	12	-0.2	14	26
MAPKKK cascade	-0.13	0.22	-10000	0	-0.65	47	47
BCL6	0.027	0.006	-10000	0	-10000	0	0
OPRM1	-0.26	0.36	-10000	0	-1.1	39	39
RETNLB	-0.26	0.36	-10000	0	-1.1	36	36
SELP	-0.25	0.36	-10000	0	-1.1	35	35
AICDA	-0.24	0.35	-10000	0	-1	38	38

×

Visual signal transduction: Rods

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
mol:K +	0.026	0.003	-10000	0	-10000	0	0
GNAT1/GTP	0.011	0.031	-10000	0	-0.3	2	2
Metarhodopsin II/Arrestin	0.013	0.05	-10000	0	-0.26	12	12
PDE6G/GNAT1/GTP	0.009	0.07	-10000	0	-0.26	26	26
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	0.008	0.047	-10000	0	-0.15	31	31
GRK1	0.021	0.015	-10000	0	-0.13	1	1
CNG Channel	-0.047	0.14	-10000	0	-0.25	141	141
mol:Na +	-0.068	0.13	-10000	0	-0.24	159	159
mol:ADP	0.021	0.015	-10000	0	-0.13	1	1
RGS9-1/Gbeta5/R9AP	0.019	0.088	-10000	0	-0.27	40	40
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	-0.058	0.14	-10000	0	-0.25	159	159
CNGB1	-0.072	0.14	-10000	0	-0.24	176	176
RDH5	0.016	0.038	-10000	0	-0.13	31	31
SAG	-0.009	0.016	-10000	0	-10000	0	0
mol:Ca2+	-0.1	0.11	0.31	3	-0.31	46	49
Na + (4 Units)	-0.079	0.12	-10000	0	-0.23	153	153
RGS9	-0.011	0.12	-10000	0	-0.39	44	44
GNB1/GNGT1	0.02	0.016	-10000	0	-10000	0	0
GNAT1/GDP	0.026	0.081	-10000	0	-0.23	40	40
GUCY2D	0.007	0.032	-10000	0	-0.13	16	16
GNGT1	-0.012	0.011	-10000	0	-10000	0	0
GUCY2F	0.011	0.024	-10000	0	-10000	0	0
GNB5	0.026	0.003	-10000	0	-10000	0	0
mol:GMP (4 units)	-0.018	0.087	0.15	2	-0.24	59	61
mol:11-cis-retinal	0.016	0.038	-10000	0	-0.13	31	31
mol:cGMP	-0.006	0.11	-10000	0	-0.24	80	80
GNB1	0.022	0.01	-10000	0	-10000	0	0
Rhodopsin	0.013	0.063	-10000	0	-0.29	12	12
SLC24A1	0.026	0.003	-10000	0	-10000	0	0
CNGA1	-0.018	0.12	-10000	0	-0.32	63	63
Metarhodopsin II	0.018	0.046	-10000	0	-0.23	12	12
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.003	0.12	-10000	0	-0.25	82	82
RGS9BP	0.017	0.05	-10000	0	-0.39	7	7
Metarhodopsin II/Transducin	-0.001	0.043	-10000	0	-0.25	11	11
GCAP Family/Ca ++	-0.007	0.11	-10000	0	-0.23	93	93
PDE6A/B	0.001	0.095	-10000	0	-0.31	37	37
mol:Pi	0.017	0.088	-10000	0	-0.27	40	40
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	0.023	0.03	-10000	0	-0.18	2	2
PDE6B	0.002	0.092	-10000	0	-0.28	40	40
PDE6A	0	0.088	-10000	0	-0.43	17	17
PDE6G	-0.001	0.1	-10000	0	-0.32	39	39
RHO	-0.003	0.077	-10000	0	-0.21	46	46
PDE6	0.009	0.12	-10000	0	-0.24	88	88
GUCA1A	-0.061	0.15	-10000	0	-0.43	68	68
GC2/GCAP Family	0.006	0.12	-10000	0	-0.25	82	82
GUCA1C	-0.007	0.029	-10000	0	-0.13	16	16
GUCA1B	0.012	0.079	-10000	0	-0.41	17	17

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	-0.026	0.11	-10000	0	-0.41	18	18
ACTA1	-0.054	0.13	0.22	2	-0.33	70	72
NUMA1	-0.027	0.11	-10000	0	-0.4	19	19
SPTAN1	-0.049	0.13	0.24	3	-0.33	66	69
LIMK1	-0.028	0.14	0.22	13	-0.33	62	75
BIRC3	-0.002	0.099	-10000	0	-0.3	42	42
BIRC2	0.025	0.005	-10000	0	-10000	0	0
BAX	0.021	0.01	-10000	0	-10000	0	0
CASP10	-0.055	0.097	0.16	1	-0.28	71	72
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.026	0.001	-10000	0	-10000	0	0
PTK2	-0.03	0.12	-10000	0	-0.34	31	31
DIABLO	0.026	0.004	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.048	0.13	0.24	3	-0.33	66	69
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.026	0.003	-10000	0	-10000	0	0
GSN	-0.054	0.13	0.22	4	-0.33	72	76
MADD	0.025	0.005	-10000	0	-10000	0	0
TFAP2A	-0.13	0.29	-10000	0	-0.59	136	136
BID	-0.024	0.066	0.11	1	-0.18	70	71
MAP3K1	-0.011	0.065	-10000	0	-0.44	5	5
TRADD	0.025	0.02	-10000	0	-0.43	1	1
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.033	0.016	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.048	0.13	0.18	11	-0.33	68	79
CASP9	0.022	0.012	-10000	0	-0.13	1	1
DNA repair	0.011	0.056	0.23	9	-0.15	9	18
neuron apoptosis	0.016	0.064	-10000	0	-0.62	4	4
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.037	0.13	0.22	1	-0.31	71	72
APAF1	0.026	0.003	-10000	0	-10000	0	0
CASP6	-0.013	0.16	-10000	0	-0.92	12	12
TRAF2	0.026	0.005	-10000	0	-10000	0	0
ICAD/CAD	-0.046	0.13	0.31	8	-0.31	70	78
CASP7	-0.009	0.096	0.24	21	-0.26	32	53
KRT18	-0.067	0.21	-10000	0	-0.57	73	73
apoptosis	-0.051	0.14	0.29	2	-0.45	32	34
DFFA	-0.049	0.13	0.19	6	-0.32	70	76
DFFB	-0.049	0.13	0.19	5	-0.32	70	75
PARP1	-0.011	0.056	0.15	9	-0.23	9	18
actin filament polymerization	0.025	0.13	0.31	62	-0.25	10	72
TNF	-0.06	0.16	-10000	0	-0.26	151	151
CYCS	-0.011	0.056	0.19	4	-0.19	12	16
SATB1	-0.014	0.16	-10000	0	-0.86	12	12
SLK	-0.052	0.13	0.33	1	-0.33	70	71
p15 BID/BAX	-0.011	0.063	-10000	0	-0.19	23	23
CASP2	0.024	0.11	0.21	86	-0.32	14	100
JNK cascade	0.011	0.065	0.43	5	-10000	0	5
CASP3	-0.055	0.13	0.18	3	-0.34	71	74
LMNB2	0.025	0.11	0.23	11	-0.39	14	25
RIPK1	0.026	0.003	-10000	0	-10000	0	0
CASP4	0.016	0.044	-10000	0	-0.16	26	26
Mammalian IAPs/DIABLO	0.05	0.064	-10000	0	-0.24	23	23
negative regulation of DNA binding	-0.13	0.29	-10000	0	-0.58	136	136
stress fiber formation	-0.052	0.13	0.33	1	-0.32	70	71
GZMB	-0.052	0.12	-10000	0	-0.28	98	98
CASP1	0.003	0.049	-10000	0	-0.29	13	13
LMNB1	0.019	0.13	0.23	11	-0.42	17	28
APP	0.016	0.065	-10000	0	-0.63	4	4
TNFRSF1A	0.017	0.054	-10000	0	-0.34	10	10
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.004	0.02	-10000	0	-0.3	1	1
VIM	-0.049	0.15	0.32	1	-0.44	35	36
LMNA	0.027	0.11	0.24	6	-0.44	8	14
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.009	0.095	-10000	0	-0.34	18	18
LRDD	0	0	-10000	0	-10000	0	0
SREBF1	-0.059	0.13	-10000	0	-0.32	77	77
APAF-1/Caspase 9	-0.072	0.22	-10000	0	-0.62	70	70
nuclear fragmentation during apoptosis	-0.026	0.11	-10000	0	-0.4	19	19
CFL2	-0.026	0.14	0.26	9	-0.31	62	71
GAS2	-0.054	0.13	0.19	1	-0.32	75	76
positive regulation of apoptosis	0.028	0.12	0.24	11	-0.39	15	26
PRF1	-0.014	0.12	-10000	0	-0.43	33	33

×

HIF-1-alpha transcription factor network

Figure S26. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S26. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.078	0.3	-10000	0	-0.75	52	52
HDAC7	0.027	0.004	-10000	0	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.041	0.34	-10000	0	-0.76	54	54
SMAD4	0.026	0.005	-10000	0	-10000	0	0
ID2	-0.065	0.31	-10000	0	-0.79	46	46
AP1	-0.011	0.1	-10000	0	-0.28	56	56
ABCG2	-0.067	0.32	-10000	0	-0.81	45	45
HIF1A	0.005	0.071	-10000	0	-0.35	2	2
TFF3	-0.069	0.32	-10000	0	-0.79	47	47
GATA2	0.014	0.066	-10000	0	-0.43	10	10
AKT1	-0.005	0.086	-10000	0	-0.23	15	15
response to hypoxia	-0.021	0.075	-10000	0	-0.18	43	43
MCL1	-0.065	0.31	-10000	0	-0.8	45	45
NDRG1	-0.076	0.31	-10000	0	-0.81	46	46
SERPINE1	-0.092	0.32	-10000	0	-0.78	57	57
FECH	-0.066	0.31	-10000	0	-0.8	45	45
FURIN	-0.064	0.31	-10000	0	-0.8	45	45
NCOA2	-0.004	0.11	-10000	0	-0.43	34	34
EP300	-0.015	0.13	-10000	0	-0.32	54	54
HMOX1	-0.069	0.32	-10000	0	-0.8	48	48
BHLHE40	-0.07	0.32	-10000	0	-0.81	47	47
BHLHE41	-0.07	0.32	-10000	0	-0.84	47	47
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.056	0.1	-10000	0	-0.31	1	1
ENG	0.013	0.078	0.26	4	-0.29	1	5
JUN	0.018	0.024	-10000	0	-0.13	9	9
RORA	-0.065	0.31	-10000	0	-0.8	46	46
ABCB1	-0.021	0.12	-10000	0	-0.69	10	10
TFRC	-0.065	0.31	-10000	0	-0.8	45	45
CXCR4	-0.07	0.32	-10000	0	-0.82	47	47
TF	-0.083	0.34	-10000	0	-0.83	53	53
CITED2	-0.065	0.31	-10000	0	-0.8	45	45
HIF1A/ARNT	-0.034	0.39	-10000	0	-0.92	44	44
LDHA	-0.012	0.14	-10000	0	-0.86	9	9
ETS1	-0.07	0.31	-10000	0	-0.8	44	44
PGK1	-0.065	0.31	-10000	0	-0.8	44	44
NOS2	-0.074	0.33	-10000	0	-0.82	48	48
ITGB2	-0.072	0.33	-10000	0	-0.85	46	46
ALDOA	-0.064	0.31	-10000	0	-0.79	46	46
Cbp/p300/CITED2	-0.087	0.37	-10000	0	-0.86	58	58
FOS	-0.032	0.14	-10000	0	-0.39	56	56
HK2	-0.072	0.33	-10000	0	-0.83	47	47
SP1	0.031	0.007	-10000	0	-10000	0	0
GCK	-0.1	0.42	-10000	0	-1.3	50	50
HK1	-0.064	0.31	-10000	0	-0.8	45	45
NPM1	-0.064	0.31	-10000	0	-0.8	45	45
EGLN1	-0.065	0.31	-10000	0	-0.81	44	44
CREB1	0.03	0.008	-10000	0	-10000	0	0
PGM1	-0.067	0.31	-10000	0	-0.79	45	45
SMAD3	0.027	0.004	-10000	0	-10000	0	0
EDN1	-0.075	0.27	-10000	0	-0.83	41	41
IGFBP1	-0.099	0.33	-10000	0	-0.77	63	63
VEGFA	-0.053	0.28	-10000	0	-0.66	51	51
HIF1A/JAB1	0.02	0.057	-10000	0	-0.36	1	1
CP	-0.11	0.35	-10000	0	-0.84	57	57
CXCL12	-0.067	0.31	-10000	0	-0.79	47	47
COPS5	0.026	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4	0.039	0.009	-10000	0	-10000	0	0
BNIP3	-0.066	0.31	-10000	0	-0.8	45	45
EGLN3	-0.069	0.32	-10000	0	-0.81	48	48
CA9	-0.08	0.32	-10000	0	-0.81	49	49
TERT	-0.089	0.33	-10000	0	-0.81	52	52
ENO1	-0.065	0.31	-10000	0	-0.79	45	45
PFKL	-0.064	0.31	-10000	0	-0.8	45	45
NCOA1	0.026	0.003	-10000	0	-10000	0	0
ADM	-0.075	0.32	-10000	0	-0.79	51	51
ARNT	0.005	0.068	-10000	0	-0.27	1	1
HNF4A	-0.004	0.055	-10000	0	-0.13	52	52
ADFP	-0.078	0.3	-10000	0	-0.75	52	52
SLC2A1	-0.056	0.27	-10000	0	-0.65	51	51
LEP	-0.067	0.29	-10000	0	-0.78	43	43
HIF1A/ARNT/Cbp/p300	-0.051	0.34	-10000	0	-0.77	57	57
EPO	-0.047	0.24	-10000	0	-0.72	24	24
CREBBP	-0.013	0.12	-10000	0	-0.31	52	52
HIF1A/ARNT/Cbp/p300/HDAC7	-0.038	0.34	-10000	0	-0.76	52	52
PFKFB3	-0.07	0.31	-10000	0	-0.82	43	43
NT5E	-0.067	0.32	-10000	0	-0.8	47	47

×

a4b1 and a4b7 Integrin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.023	0.012	-9999	-10000	0	0
ITGB7	0.001	0.091	-9999	-0.26	44	44
ITGA4	-0.008	0.1	-9999	-0.26	61	61
alpha4/beta7 Integrin	-0.005	0.1	-9999	-0.28	56	56
alpha4/beta1 Integrin	0.012	0.077	-9999	-0.29	26	26

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.014	0.1	-9999	-0.26	63	63
E-cadherin/beta catenin	-0.017	0.11	-9999	-0.3	59	59
CTNNB1	0.026	0.004	-9999	-10000	0	0
JUP	0.02	0.049	-9999	-0.39	7	7
CDH1	-0.046	0.15	-9999	-0.43	59	59

×

amb2 Integrin signaling

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
alphaM/beta2 Integrin/proMMP-2	-0.01	0.13	-10000	0	-0.33	54	54
alphaM/beta2 Integrin/GPIbA	-0.011	0.12	-10000	0	-0.32	56	56
alphaM/beta2 Integrin/proMMP-9	-0.035	0.14	-10000	0	-0.3	96	96
PLAUR	0.011	0.042	-10000	0	-0.43	1	1
HMGB1	0.009	0.031	-10000	0	-0.12	1	1
alphaM/beta2 Integrin/Talin	-0.003	0.12	-10000	0	-0.33	44	44
AGER	-0.008	0.092	-10000	0	-0.4	22	22
RAP1A	0.021	0.01	-10000	0	-10000	0	0
SELPLG	-0.001	0.1	-10000	0	-0.43	29	29
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.032	0.16	-10000	0	-0.28	131	131
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	-0.041	0.13	-10000	0	-0.23	133	133
CYR61	-0.015	0.1	-10000	0	-0.24	71	71
TLN1	0.026	0.005	-10000	0	-10000	0	0
Rap1/GTP	-0.024	0.12	-10000	0	-0.37	30	30
RHOA	0.026	0.004	-10000	0	-10000	0	0
P-selectin oligomer	0.003	0.042	-10000	0	-10000	0	0
MYH2	-0.039	0.11	-10000	0	-0.4	24	24
MST1R	0.02	0.049	-10000	0	-0.39	7	7
leukocyte activation during inflammatory response	-0.021	0.13	-10000	0	-0.3	73	73
APOB	-0.025	0.13	-10000	0	-0.29	77	77
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	0.013	0.067	-10000	0	-0.26	24	24
JAM3	0.024	0.007	-10000	0	-10000	0	0
GP1BA	0.014	0.072	-10000	0	-0.43	13	13
alphaM/beta2 Integrin/CTGF	-0.016	0.13	-10000	0	-0.34	57	57
alphaM/beta2 Integrin	-0.045	0.13	-10000	0	-0.42	32	32
JAM3 homodimer	0.024	0.007	-10000	0	-10000	0	0
ICAM2	0.025	0.005	-10000	0	-10000	0	0
ICAM1	0.011	0.062	-10000	0	-0.43	7	7
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.044	0.13	-10000	0	-0.42	32	32
cell adhesion	-0.011	0.12	-10000	0	-0.32	56	56
NFKB1	-0.1	0.19	-10000	0	-0.42	109	109
THY1	0.015	0.062	-10000	0	-0.43	9	9
RhoA/GDP	0.019	0.003	-10000	0	-10000	0	0
Lipoprotein(a)	-0.005	0.083	-10000	0	-0.25	44	44
alphaM/beta2 Integrin/LRP/tPA	0.007	0.12	-10000	0	-0.34	40	40
IL6	-0.12	0.23	-10000	0	-0.52	93	93
ITGB2	-0.014	0.097	-10000	0	-0.33	33	33
elevation of cytosolic calcium ion concentration	-0.008	0.12	-10000	0	-0.3	58	58
alphaM/beta2 Integrin/JAM2/JAM3	0.012	0.11	-10000	0	-0.32	39	39
JAM2	0.026	0.004	-10000	0	-10000	0	0
alphaM/beta2 Integrin/ICAM1	0.002	0.13	-10000	0	-0.28	73	73
alphaM/beta2 Integrin/uPA/Plg	-0.012	0.12	-10000	0	-0.32	53	53
RhoA/GTP	-0.037	0.12	-10000	0	-0.35	37	37
positive regulation of phagocytosis	-0.04	0.14	-10000	0	-0.39	52	52
Ron/MSP	0.015	0.083	-10000	0	-0.3	31	31
alphaM/beta2 Integrin/uPAR/uPA	-0.006	0.12	-10000	0	-0.3	58	58
alphaM/beta2 Integrin/uPAR	-0.011	0.12	-10000	0	-0.33	46	46
PLAU	-0.001	0.081	-10000	0	-0.19	64	64
PLAT	0.005	0.058	-10000	0	-0.43	2	2
actin filament polymerization	-0.036	0.11	0.19	2	-0.39	23	25
MST1	0.001	0.099	-10000	0	-0.36	32	32
alphaM/beta2 Integrin/lipoprotein(a)	-0.015	0.14	-10000	0	-0.3	73	73
TNF	-0.15	0.27	-10000	0	-0.63	101	101
RAP1B	0.026	0.004	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.02	0.13	-10000	0	-0.31	64	64
fibrinolysis	-0.013	0.12	-10000	0	-0.32	53	53
HCK	0.014	0.063	-10000	0	-0.27	19	19
dendritic cell antigen processing and presentation	-0.044	0.13	-10000	0	-0.42	32	32
VTN	0.012	0.075	-10000	0	-0.35	19	19
alphaM/beta2 Integrin/CYR61	-0.03	0.13	-10000	0	-0.31	72	72
LPA	0.005	0.039	-10000	0	-10000	0	0
LRP1	0.026	0.004	-10000	0	-10000	0	0
cell migration	-0.05	0.13	-10000	0	-0.29	94	94
FN1	0.021	0.029	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Thy1	-0.007	0.12	-10000	0	-0.33	49	49
MPO	-0.05	0.15	-10000	0	-0.43	64	64
KNG1	-0.009	0.032	-10000	0	-0.13	22	22
RAP1/GDP	0.028	0.015	-10000	0	-10000	0	0
ROCK1	-0.034	0.12	-10000	0	-0.4	23	23
ELA2	0	0	-10000	0	-10000	0	0
PLG	-0.01	0.019	-10000	0	-10000	0	0
CTGF	0.004	0.086	-10000	0	-0.43	17	17
alphaM/beta2 Integrin/Hck	-0.009	0.14	-10000	0	-0.36	50	50
ITGAM	-0.02	0.12	-10000	0	-0.41	36	36
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.005	0.15	-10000	0	-0.4	50	50
HP	-0.034	0.13	-10000	0	-0.24	113	113
leukocyte adhesion	-0.031	0.14	-10000	0	-0.35	57	57
SELP	0.003	0.042	-10000	0	-10000	0	0

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.058	0.18	0.26	9	-0.41	83	92
IKBKB	0.015	0.09	0.24	21	-0.31	3	24
AKT1	-0.022	0.1	0.26	24	-0.22	33	57
IKBKG	0.004	0.093	0.24	14	-0.27	14	28
CALM1	-0.04	0.14	0.24	2	-0.46	36	38
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
MAP3K1	-0.033	0.18	0.3	17	-0.48	50	67
MAP3K7	0.026	0.004	-10000	0	-10000	0	0
mol:Ca2+	-0.041	0.15	0.22	4	-0.4	56	60
DOK1	0.025	0.021	-10000	0	-0.28	2	2
AP-1	-0.044	0.12	0.22	4	-0.27	74	78
LYN	0.021	0.035	-10000	0	-0.43	2	2
BLNK	-0.021	0.13	-10000	0	-0.43	49	49
SHC1	0.024	0.014	-10000	0	-10000	0	0
BCR complex	-0.006	0.096	-10000	0	-0.27	51	51
CD22	-0.065	0.15	-10000	0	-0.43	53	53
CAMK2G	-0.037	0.14	0.26	4	-0.44	34	38
CSNK2A1	0.025	0.005	-10000	0	-10000	0	0
INPP5D	0.022	0.037	-10000	0	-0.28	6	6
SHC/GRB2/SOS1	-0.027	0.11	-10000	0	-0.25	68	68
GO:0007205	-0.042	0.16	0.22	3	-0.41	55	58
SYK	0.009	0.083	-10000	0	-0.35	23	23
ELK1	-0.039	0.15	0.22	2	-0.47	37	39
NFATC1	-0.043	0.14	0.27	6	-0.42	49	55
B-cell antigen/BCR complex	-0.006	0.096	-10000	0	-0.27	51	51
PAG1/CSK	0.036	0.01	-10000	0	-10000	0	0
NFKBIB	0.017	0.046	0.13	23	-0.13	13	36
HRAS	-0.031	0.14	0.26	6	-0.44	31	37
NFKBIA	0.016	0.047	0.12	26	-0.13	13	39
NF-kappa-B/RelA/I kappa B beta	0.022	0.041	0.13	23	-10000	0	23
RasGAP/Csk	-0.002	0.12	-10000	0	-0.24	96	96
mol:GDP	-0.037	0.15	0.22	3	-0.44	45	48
PTEN	0.025	0.006	-10000	0	-10000	0	0
CD79B	-0.005	0.099	-10000	0	-0.26	54	54
NF-kappa-B/RelA/I kappa B alpha	0.022	0.041	0.13	23	-10000	0	23
GRB2	0.025	0.006	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.059	0.18	0.34	4	-0.51	50	54
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
mol:IP3	-0.044	0.16	0.22	3	-0.41	58	61
CSK	0.026	0.003	-10000	0	-10000	0	0
FOS	-0.059	0.16	0.22	2	-0.45	44	46
CHUK	-0.006	0.098	0.24	12	-0.3	18	30
IBTK	0.026	0.004	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.002	0.15	0.24	12	-0.46	28	40
PTPN6	-0.068	0.15	0.22	2	-0.45	52	54
RELA	0.025	0.005	-10000	0	-10000	0	0
BCL2A1	0.007	0.038	0.12	5	-0.12	2	7
VAV2	-0.053	0.15	0.23	1	-0.47	47	48
ubiquitin-dependent protein catabolic process	0.019	0.046	0.13	24	-0.13	13	37
BTK	-0.018	0.21	-10000	0	-1.1	18	18
CD19	-0.056	0.14	-10000	0	-0.39	60	60
MAP4K1	0.013	0.061	-10000	0	-0.34	13	13
CD72	0.017	0.048	-10000	0	-0.43	4	4
PAG1	0.025	0.006	-10000	0	-10000	0	0
MAPK14	-0.026	0.16	0.27	19	-0.41	49	68
SH3BP5	0.024	0.029	-10000	0	-0.43	2	2
PIK3AP1	-0.041	0.16	-10000	0	-0.47	46	46
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.06	0.23	-10000	0	-0.66	46	46
RAF1	-0.028	0.13	0.26	5	-0.42	29	34
RasGAP/p62DOK/SHIP	-0.002	0.12	-10000	0	-0.23	98	98
CD79A	-0.001	0.086	-10000	0	-0.25	42	42
re-entry into mitotic cell cycle	-0.044	0.11	0.22	4	-0.27	74	78
RASA1	0.026	0.003	-10000	0	-10000	0	0
MAPK3	-0.024	0.11	0.24	6	-0.41	20	26
MAPK1	-0.023	0.11	0.23	6	-0.41	19	25
CD72/SHP1	-0.056	0.16	0.27	12	-0.43	51	63
NFKB1	0.026	0.004	-10000	0	-10000	0	0
MAPK8	-0.031	0.16	0.28	17	-0.41	52	69
actin cytoskeleton organization	-0.027	0.15	0.3	19	-0.41	43	62
NF-kappa-B/RelA	0.044	0.079	0.24	18	-0.21	8	26
Calcineurin	-0.011	0.13	0.22	1	-0.43	29	30
PI3K	-0.067	0.13	-10000	0	-0.37	56	56
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.043	0.17	-10000	0	-0.44	56	56
SOS1	0.026	0.002	-10000	0	-10000	0	0
Bam32/HPK1	-0.068	0.27	-10000	0	-0.8	55	55
DAPP1	-0.095	0.31	-10000	0	-0.92	55	55
cytokine secretion	-0.04	0.14	0.26	6	-0.39	49	55
mol:DAG	-0.044	0.16	0.22	3	-0.41	58	61
PLCG2	0.018	0.055	-10000	0	-0.29	13	13
MAP2K1	-0.026	0.12	0.24	6	-0.43	22	28
B-cell antigen/BCR complex/FcgammaRIIB	-0.028	0.13	-10000	0	-0.25	115	115
mol:PI-3-4-5-P3	-0.056	0.094	0.18	1	-0.29	46	47
ETS1	-0.026	0.13	0.26	9	-0.41	32	41
B-cell antigen/BCR complex/LYN/SYK/BLNK	0	0.13	-10000	0	-0.26	89	89
B-cell antigen/BCR complex/LYN	-0.048	0.15	-10000	0	-0.42	56	56
MALT1	0.026	0.004	-10000	0	-10000	0	0
TRAF6	0.024	0.021	-10000	0	-0.43	1	1
RAC1	-0.033	0.15	0.28	15	-0.44	42	57
B-cell antigen/BCR complex/LYN/SYK	-0.049	0.17	0.27	1	-0.43	61	62
CARD11	-0.022	0.18	0.25	23	-0.51	36	59
FCGR2B	-0.05	0.15	-10000	0	-0.26	135	135
PPP3CA	0.025	0.011	-10000	0	-0.13	2	2
BCL10	0.021	0.01	-10000	0	-10000	0	0
IKK complex	0.01	0.05	0.14	25	-0.12	5	30
PTPRC	-0.003	0.1	-10000	0	-0.43	24	24
PDPK1	-0.034	0.079	0.2	14	-0.21	36	50
PPP3CB	0.024	0.013	-10000	0	-10000	0	0
PPP3CC	0.025	0.005	-10000	0	-10000	0	0
POU2F2	0.021	0.033	0.15	18	-10000	0	18

×

Glypican 2 network

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
MDK	-0.002	0.097	-9999	-0.27	48	48
GPC2	0.004	0.084	-9999	-0.37	22	22
GPC2/Midkine	0.002	0.091	-9999	-0.31	36	36
neuron projection morphogenesis	0.002	0.09	-9999	-0.31	36	36

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	-0.01	0.084	-10000	0	-0.23	62	62
epithelial cell differentiation	0.024	0.086	-10000	0	-0.22	55	55
CYFIP2	0.022	0.037	-10000	0	-0.28	6	6
ENAH	-0.024	0.061	0.27	3	-10000	0	3
EGFR	-0.016	0.12	-10000	0	-0.4	46	46
EPHA2	0.012	0.045	-10000	0	-0.15	29	29
MYO6	-0.014	0.08	0.18	21	-0.21	55	76
CTNNB1	0.026	0.004	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.045	0.028	-10000	0	-0.23	3	3
AQP5	-0.063	0.16	-10000	0	-0.44	69	69
CTNND1	0.026	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.013	0.077	0.18	18	-0.21	51	69
regulation of calcium-dependent cell-cell adhesion	-0.015	0.081	0.18	19	-0.21	57	76
EGF	-0.01	0.11	-10000	0	-0.43	33	33
NCKAP1	0.026	0.002	-10000	0	-10000	0	0
AQP3	-0.019	0.1	-10000	0	-0.46	16	16
cortical microtubule organization	0.024	0.086	-10000	0	-0.22	55	55
GO:0000145	-0.026	0.07	0.16	20	-0.2	51	71
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.029	0.088	-10000	0	-0.22	55	55
MLLT4	0.024	0.021	-10000	0	-0.43	1	1
ARF6/GDP	-0.038	0.056	-10000	0	-0.2	35	35
ARF6	0.026	0.004	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.054	0.036	-10000	0	-0.25	3	3
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.027	0.085	-10000	0	-0.34	18	18
PVRL2	0.02	0.023	-10000	0	-0.43	1	1
ZYX	-0.013	0.069	0.18	11	-0.21	44	55
ARF6/GTP	0.059	0.038	-10000	0	-0.24	3	3
CDH1	-0.046	0.15	-10000	0	-0.43	59	59
EGFR/EGFR/EGF/EGF	-0.02	0.12	-10000	0	-0.24	105	105
RhoA/GDP	0.026	0.083	-10000	0	-0.21	55	55
actin cytoskeleton organization	-0.028	0.075	0.17	21	-0.21	49	70
IGF-1R heterotetramer	0.026	0.004	-10000	0	-10000	0	0
GIT1	0.026	0.002	-10000	0	-10000	0	0
IGF1R	0.026	0.004	-10000	0	-10000	0	0
IGF1	0.012	0.076	-10000	0	-0.34	20	20
DIAPH1	0.02	0.12	-10000	0	-0.6	8	8
Wnt receptor signaling pathway	-0.024	0.086	0.22	55	-10000	0	55
RHOA	0.026	0.004	-10000	0	-10000	0	0
RhoA/GTP	-0.038	0.056	-10000	0	-0.2	35	35
CTNNA1	0.026	0.004	-10000	0	-10000	0	0
VCL	-0.029	0.077	0.17	21	-0.22	49	70
EFNA1	0.024	0.014	-10000	0	-0.13	4	4
LPP	-0.036	0.077	0.17	19	-0.21	61	80
Ephrin A1/EPHA2	0.013	0.079	-10000	0	-0.2	54	54
SEC6/SEC8	-0.015	0.06	-10000	0	-0.21	26	26
MGAT3	-0.016	0.082	0.18	19	-0.21	57	76
HGF/MET	-0.025	0.12	-10000	0	-0.25	95	95
HGF	-0.009	0.091	-10000	0	-0.2	69	69
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.01	0.085	-10000	0	-0.23	62	62
actin cable formation	-0.004	0.096	0.32	13	-0.26	11	24
KIAA1543	-0.032	0.076	0.17	13	-0.22	55	68
KIFC3	-0.016	0.079	0.18	16	-0.21	55	71
NCK1	0.025	0.02	-10000	0	-0.43	1	1
EXOC3	0.026	0.005	-10000	0	-10000	0	0
ACTN1	-0.019	0.08	0.18	19	-0.21	56	75
NCK1/GIT1	0.038	0.016	-10000	0	-0.3	1	1
mol:GDP	0.024	0.086	-10000	0	-0.22	55	55
EXOC4	0.02	0.011	-10000	0	-10000	0	0
STX4	-0.014	0.079	0.18	19	-0.21	53	72
PIP5K1C	-0.013	0.078	0.18	18	-0.21	51	69
LIMA1	0.019	0.056	-10000	0	-0.43	8	8
ABI1	0.023	0.008	-10000	0	-10000	0	0
ROCK1	-0.021	0.082	0.4	6	-10000	0	6
adherens junction assembly	-0.01	0.089	0.27	10	-0.38	6	16
IGF-1R heterotetramer/IGF1	0.014	0.09	-10000	0	-0.22	62	62
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.03	0.027	-10000	0	-0.3	2	2
MET	-0.047	0.14	-10000	0	-0.43	52	52
PLEKHA7	-0.019	0.085	0.19	1	-0.23	55	56
mol:GTP	0.052	0.036	-10000	0	-0.25	3	3
establishment of epithelial cell apical/basal polarity	0.02	0.12	0.33	27	-0.37	1	28
cortical actin cytoskeleton stabilization	-0.01	0.084	-10000	0	-0.23	62	62
regulation of cell-cell adhesion	-0.028	0.075	0.17	21	-0.21	49	70
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.01	0.085	-10000	0	-0.23	62	62

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.025	0.006	-10000	0	-10000	0	0
EGFR	-0.016	0.12	-10000	0	-0.4	46	46
EGF/EGFR	-0.008	0.11	-10000	0	-0.24	88	88
EGF/EGFR dimer/SHC/GRB2/SOS1	0.022	0.1	-10000	0	-0.24	64	64
mol:GTP	0	0	-10000	0	-10000	0	0
EDNRA	0.006	0.083	-10000	0	-0.28	32	32
response to oxidative stress	0	0	-10000	0	-10000	0	0
EGF	-0.01	0.11	-10000	0	-0.43	33	33
EGF/EGFR dimer/SHC	0	0.11	-10000	0	-0.27	67	67
mol:GDP	0.016	0.1	-10000	0	-0.23	64	64
mol:Ca2+	0	0	-10000	0	-10000	0	0
EDN1	0.002	0.086	-10000	0	-0.23	47	47
GRB2/SOS1	0.037	0.009	-10000	0	-10000	0	0
HRAS/GTP	0.004	0.087	-10000	0	-0.22	63	63
SHC1	0.024	0.014	-10000	0	-10000	0	0
HRAS/GDP	0.015	0.096	-10000	0	-0.22	63	63
FRAP1	-0.034	0.075	0.11	7	-0.22	64	71
EGF/EGFR dimer	-0.02	0.12	-10000	0	-0.32	69	69
SOS1	0.026	0.002	-10000	0	-10000	0	0
GRB2	0.025	0.006	-10000	0	-10000	0	0
ETA receptor/Endothelin-1	0.005	0.088	-10000	0	-0.3	34	34

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.042	0.2	-9999	-0.47	69	69
MAP3K8	0.015	0.047	-9999	-0.2	17	17
FOS	-0.041	0.18	-9999	-0.44	70	70
PRKCA	0.02	0.024	-9999	-0.43	1	1
PTPN7	-0.054	0.15	-9999	-0.29	122	122
HRAS	0.024	0.006	-9999	-10000	0	0
PRKCB	-0.011	0.098	-9999	-0.22	68	68
NRAS	0.021	0.01	-9999	-10000	0	0
RAS family/GTP	0.034	0.026	-9999	-10000	0	0
MAPK3	-0.032	0.16	-9999	-0.43	66	66
MAP2K1	0.003	0.1	-9999	-0.44	20	20
ELK1	0.021	0.017	-9999	-10000	0	0
BRAF	-0.005	0.083	-9999	-0.39	21	21
mol:GTP	0	0.001	-9999	-0.004	59	59
MAPK1	-0.035	0.17	-9999	-0.43	69	69
RAF1	-0.001	0.086	-9999	-0.41	19	19
KRAS	0.025	0.005	-9999	-10000	0	0

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.029	0.025	-10000	0	-0.28	2	2
Necdin/E2F1	0.013	0.082	-10000	0	-0.31	29	29
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.015	0.11	-10000	0	-0.24	73	73
NGF (dimer)/p75(NTR)/BEX1	-0.018	0.13	-10000	0	-0.28	91	91
NT-4/5 (dimer)/p75(NTR)	-0.005	0.089	-10000	0	-0.29	40	40
IKBKB	0.025	0.005	-10000	0	-10000	0	0
AKT1	-0.029	0.092	0.18	9	-0.24	71	80
IKBKG	0.026	0.003	-10000	0	-10000	0	0
BDNF	-0.01	0.089	-10000	0	-0.43	14	14
MGDIs/NGR/p75(NTR)/LINGO1	-0.002	0.13	-10000	0	-0.3	78	78
FURIN	0.026	0.004	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	0.01	0.098	-10000	0	-0.26	53	53
LINGO1	0.001	0.1	-10000	0	-0.43	28	28
Sortilin/TRAF6/NRIF	0.025	0.02	-10000	0	-10000	0	0
proBDNF (dimer)	-0.01	0.089	-10000	0	-0.43	14	14
NTRK1	0.016	0.055	-10000	0	-0.22	20	20
RTN4R	-0.006	0.11	-10000	0	-0.43	31	31
neuron apoptosis	-0.066	0.16	0.29	9	-0.45	38	47
IRAK1	0.026	0.003	-10000	0	-10000	0	0
SHC1	-0.038	0.1	0.19	1	-0.28	73	74
ARHGDIA	0.025	0.005	-10000	0	-10000	0	0
RhoA/GTP	0.019	0.003	-10000	0	-10000	0	0
Gamma Secretase	0.063	0.032	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.001	0.12	-10000	0	-0.25	78	78
MAGEH1	0.018	0.06	-10000	0	-0.43	9	9
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.013	0.14	-10000	0	-0.27	98	98
Mammalian IAPs/DIABLO	0.05	0.064	-10000	0	-0.24	23	23
proNGF (dimer)	-0.025	0.13	-10000	0	-0.43	46	46
MAGED1	0.026	0.002	-10000	0	-10000	0	0
APP	0.026	0.004	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.003	0.033	-10000	0	-0.16	12	12
ZNF274	0.021	0.01	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.017	0.094	-10000	0	-0.24	69	69
NGF	-0.025	0.13	-10000	0	-0.43	46	46
cell cycle arrest	-0.037	0.089	0.26	10	-0.21	71	81
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.021	0.099	-10000	0	-0.25	71	71
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.012	0.081	-10000	0	-0.24	40	40
NCSTN	0.026	0.004	-10000	0	-10000	0	0
mol:GTP	-0.017	0.12	-10000	0	-0.28	73	73
PSENEN	0.022	0.01	-10000	0	-10000	0	0
mol:ceramide	-0.032	0.097	0.18	7	-0.25	73	80
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.021	0.094	-10000	0	-0.31	23	23
p75(NTR)/beta APP	0.005	0.09	-10000	0	-0.3	35	35
BEX1	0.01	0.084	-10000	0	-0.43	18	18
mol:GDP	-0.044	0.1	-10000	0	-0.27	76	76
NGF (dimer)	-0.025	0.13	-10000	0	-0.25	117	117
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.013	0.12	-10000	0	-0.27	76	76
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
RAC1/GTP	-0.006	0.094	-10000	0	-0.23	67	67
MYD88	0.019	0.054	-10000	0	-0.43	7	7
CHUK	0.025	0.005	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.007	0.12	-10000	0	-0.27	76	76
RHOB	0.025	0.012	-10000	0	-0.13	3	3
RHOA	0.026	0.004	-10000	0	-10000	0	0
MAGE-G1/E2F1	0.028	0.044	-10000	0	-0.3	6	6
NT3 (dimer)	0.006	0.032	-10000	0	-10000	0	0
TP53	-0.021	0.1	0.22	32	-0.24	49	81
PRDM4	-0.032	0.099	0.18	7	-0.25	74	81
BDNF (dimer)	-0.017	0.12	-10000	0	-0.26	93	93
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
SORT1	0.02	0.022	-10000	0	-0.43	1	1
activation of caspase activity	0.011	0.11	-10000	0	-0.24	73	73
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.005	0.11	-10000	0	-0.25	74	74
RHOC	0.02	0.023	-10000	0	-0.28	2	2
XIAP	0.026	0.001	-10000	0	-10000	0	0
MAPK10	-0.017	0.13	0.3	25	-0.32	39	64
DIABLO	0.026	0.004	-10000	0	-10000	0	0
SMPD2	-0.032	0.098	0.18	7	-0.25	73	80
APH1B	0.026	0.003	-10000	0	-10000	0	0
APH1A	0.026	0.004	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.007	0.12	-10000	0	-0.27	77	77
PSEN1	0.025	0.005	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.032	0.016	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.002	0.091	-10000	0	-0.3	38	38
MAPK8	-0.026	0.13	0.31	14	-0.32	40	54
MAPK9	-0.015	0.13	0.3	26	-0.33	36	62
APAF1	0.026	0.003	-10000	0	-10000	0	0
NTF3	0.006	0.032	-10000	0	-10000	0	0
NTF4	-0.003	0.033	-10000	0	-0.16	12	12
NDN	-0.003	0.11	-10000	0	-0.43	33	33
RAC1/GDP	0.017	0.007	-10000	0	-10000	0	0
RhoA-B-C/GDP	0.011	0.1	-10000	0	-0.22	72	72
p75 CTF/Sortilin/TRAF6/NRIF	0.044	0.045	-10000	0	-0.24	6	6
RhoA-B-C/GTP	-0.017	0.12	-10000	0	-0.28	73	73
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.026	0.095	-10000	0	-0.24	46	46
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.022	0.097	-10000	0	-0.25	47	47
PRKACB	0.021	0.01	-10000	0	-10000	0	0
proBDNF (dimer)/p75 ECD	0.007	0.077	-10000	0	-0.32	18	18
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.002	0.099	-10000	0	-0.3	42	42
BIRC2	0.025	0.005	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.05	0.1	0.14	7	-0.27	77	84
BAD	-0.018	0.14	0.29	28	-0.33	36	64
RIPK2	0.024	0.007	-10000	0	-10000	0	0
NGFR	-0.017	0.12	-10000	0	-0.28	72	72
CYCS	-0.026	0.09	0.22	8	-0.24	61	69
ADAM17	0.022	0.045	-10000	0	-0.43	5	5
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.005	0.11	-10000	0	-0.25	66	66
BCL2L11	-0.021	0.13	0.28	25	-0.33	37	62
BDNF (dimer)/p75(NTR)	-0.02	0.11	-10000	0	-0.3	53	53
PI3K	0.007	0.11	-10000	0	-0.25	72	72
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.006	0.11	-10000	0	-0.25	74	74
NDNL2	0.026	0.003	-10000	0	-10000	0	0
YWHAE	0.026	0.002	-10000	0	-10000	0	0
PRKCI	0.026	0.003	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.034	0.13	-10000	0	-0.32	77	77
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.006	0.11	-10000	0	-0.25	73	73
TRAF6	0.024	0.021	-10000	0	-0.43	1	1
RAC1	0.023	0.009	-10000	0	-10000	0	0
PRKCZ	0.007	0.076	-10000	0	-0.43	14	14
PLG	-0.01	0.019	-10000	0	-10000	0	0
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.044	0.11	0.24	2	-0.28	81	83
SQSTM1	0.026	0.004	-10000	0	-10000	0	0
NGFRAP1	0.026	0.002	-10000	0	-10000	0	0
CASP3	-0.018	0.13	0.28	26	-0.32	38	64
E2F1	0.014	0.056	-10000	0	-0.21	24	24
CASP9	0.022	0.012	-10000	0	-0.13	1	1
IKK complex	-0.021	0.13	-10000	0	-0.31	43	43
NGF (dimer)/TRKA	-0.012	0.1	-10000	0	-0.3	53	53
MMP7	-0.073	0.16	-10000	0	-0.29	150	150
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.012	0.11	-10000	0	-0.24	71	71
MMP3	-0.005	0.047	-10000	0	-0.43	1	1
APAF-1/Caspase 9	-0.029	0.082	-10000	0	-0.3	15	15

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.008	0.17	0.36	11	-1.1	9	20
VDR	-0.014	0.11	-10000	0	-0.26	71	71
FAM120B	0.025	0.005	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.045	0.15	-10000	0	-0.32	96	96
RXRs/LXRs/DNA/Oxysterols	-0.073	0.21	-10000	0	-0.47	97	97
MED1	0.026	0.003	-10000	0	-10000	0	0
mol:9cRA	-0.006	0.02	-10000	0	-0.098	1	1
RARs/THRs/DNA/Src-1	0.023	0.041	-10000	0	-0.22	14	14
RXRs/NUR77	0.011	0.11	-10000	0	-0.25	59	59
RXRs/PPAR	-0.013	0.098	-10000	0	-0.26	58	58
NCOR2	0.026	0.003	-10000	0	-10000	0	0
VDR/VDR/Vit D3	-0.009	0.08	-10000	0	-0.29	33	33
RARs/VDR/DNA/Vit D3	0.042	0.071	-10000	0	-0.22	32	32
RARA	0.026	0.003	-10000	0	-10000	0	0
NCOA1	0.026	0.003	-10000	0	-10000	0	0
VDR/VDR/DNA	-0.014	0.11	-10000	0	-0.26	71	71
RARs/RARs/DNA/9cRA	0.035	0.032	-10000	0	-0.22	3	3
RARG	0.025	0.008	-10000	0	-10000	0	0
RPS6KB1	0.028	0.12	0.58	17	-0.43	9	26
RARs/THRs/DNA/SMRT	0.022	0.041	-10000	0	-0.22	14	14
THRA	0.023	0.035	-10000	0	-0.43	3	3
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	-0.009	0.08	-10000	0	-0.29	33	33
RXRs/PPAR/9cRA/PGJ2/DNA	-0.004	0.11	-10000	0	-0.2	95	95
NR1H4	-0.042	0.13	-10000	0	-0.24	128	128
RXRs/LXRs/DNA	0.011	0.12	-10000	0	-0.23	83	83
NR1H2	0.015	0.026	-10000	0	-10000	0	0
NR1H3	0.015	0.031	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.003	0.12	-10000	0	-0.24	79	79
NR4A1	0.012	0.062	-10000	0	-0.43	7	7
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.037	0.11	-10000	0	-0.25	85	85
RXRG	-0.036	0.14	-10000	0	-0.4	63	63
RXR alpha/CCPG	0.027	0.028	-10000	0	-10000	0	0
RXRA	0.015	0.029	-10000	0	-10000	0	0
RXRB	0.015	0.031	-10000	0	-0.1	1	1
THRB	0.015	0.059	-10000	0	-0.23	22	22
PPARG	0.009	0.081	-10000	0	-0.43	16	16
PPARD	0.026	0.003	-10000	0	-10000	0	0
TNF	-0.15	0.37	-10000	0	-0.96	81	81
mol:Oxysterols	-0.006	0.019	-10000	0	-10000	0	0
cholesterol transport	-0.072	0.21	-10000	0	-0.46	97	97
PPARA	0.026	0.004	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.023	0.035	-10000	0	-0.43	3	3
RXRs/NUR77/BCL2	-0.016	0.094	-10000	0	-0.25	59	59
SREBF1	-0.085	0.24	-10000	0	-0.87	30	30
RXRs/RXRs/DNA/9cRA	-0.004	0.11	-10000	0	-0.2	97	97
ABCA1	-0.086	0.24	-10000	0	-0.55	84	84
RARs/THRs	0.067	0.05	-10000	0	-0.22	13	13
RXRs/FXR	-0.01	0.14	-10000	0	-0.26	103	103
BCL2	0.021	0.045	-10000	0	-0.43	5	5

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.013	0.089	-10000	0	-0.22	61	61
NF kappa B1 p50/RelA/I kappa B alpha	0	0.11	0.24	15	-0.31	33	48
AP1	-0.03	0.1	-10000	0	-0.23	92	92
mol:PIP3	-0.036	0.088	-10000	0	-0.24	60	60
AKT1	0.001	0.1	0.27	17	-0.34	5	22
PTK2B	-0.005	0.09	0.17	14	-0.22	49	63
RHOA	0.004	0.079	0.22	17	-0.36	7	24
PIK3CB	0.026	0.003	-10000	0	-10000	0	0
mol:Ca2+	-0.004	0.071	0.21	22	-0.28	10	32
MAGI3	0.02	0.022	-10000	0	-0.43	1	1
RELA	0.025	0.005	-10000	0	-10000	0	0
apoptosis	-0.021	0.087	-10000	0	-0.27	52	52
HRAS/GDP	0.018	0.005	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.008	0.088	0.21	8	-0.26	20	28
NF kappa B1 p50/RelA	-0.023	0.11	-10000	0	-0.32	37	37
endothelial cell migration	-0.022	0.11	-10000	0	-0.3	57	57
ADCY4	-0.014	0.12	-10000	0	-0.35	52	52
ADCY5	-0.015	0.12	-10000	0	-0.34	52	52
ADCY6	-0.013	0.12	-10000	0	-0.34	52	52
ADCY7	-0.014	0.12	-10000	0	-0.34	52	52
ADCY1	-0.032	0.12	-10000	0	-0.36	50	50
ADCY2	-0.018	0.12	-10000	0	-0.35	54	54
ADCY3	-0.013	0.12	-10000	0	-0.34	52	52
ADCY8	-0.035	0.14	-10000	0	-0.39	59	59
ADCY9	-0.014	0.12	-10000	0	-0.34	52	52
GSK3B	-0.006	0.087	0.18	9	-0.25	24	33
arachidonic acid secretion	-0.02	0.12	-10000	0	-0.32	60	60
GNG2	0.022	0.04	-10000	0	-0.43	4	4
TRIP6	0.013	0.031	-10000	0	-0.21	7	7
GNAO1	-0.018	0.089	-10000	0	-0.25	61	61
HRAS	0.025	0.006	-10000	0	-10000	0	0
NFKBIA	-0.018	0.12	0.24	17	-0.34	35	52
GAB1	0.025	0.02	-10000	0	-0.43	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	0.029	0.11	-10000	0	-0.84	7	7
JUN	0.019	0.023	-10000	0	-0.13	9	9
LPA/LPA2/NHERF2	0.028	0.039	-10000	0	-0.25	7	7
TIAM1	0.017	0.13	-10000	0	-1	7	7
PIK3R1	0.026	0.004	-10000	0	-10000	0	0
mol:IP3	-0.008	0.066	0.2	15	-0.29	10	25
PLCB3	0.017	0.048	0.18	23	-0.23	7	30
FOS	-0.031	0.14	-10000	0	-0.43	48	48
positive regulation of mitosis	-0.02	0.12	-10000	0	-0.32	60	60
LPA/LPA1-2-3	0.007	0.094	-10000	0	-0.23	63	63
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0	-10000	0	-10000	0	0
BCAR1	0.025	0.02	-10000	0	-0.43	1	1
stress fiber formation	0.002	0.097	0.2	10	-0.32	11	21
GNAZ	-0.014	0.084	-10000	0	-0.25	54	54
EGFR/PI3K-beta/Gab1	-0.03	0.095	-10000	0	-0.24	60	60
positive regulation of dendritic cell cytokine production	0.006	0.093	-10000	0	-0.23	63	63
LPA/LPA2/MAGI-3	0.021	0.042	-10000	0	-0.25	8	8
ARHGEF1	0.015	0.097	0.2	60	-0.2	48	108
GNAI2	-0.015	0.085	-10000	0	-0.25	55	55
GNAI3	-0.003	0.062	-10000	0	-0.26	26	26
GNAI1	-0.015	0.083	-10000	0	-0.25	53	53
LPA/LPA3	0.002	0.036	-10000	0	-0.17	9	9
LPA/LPA2	0.013	0.042	-10000	0	-0.2	15	15
LPA/LPA1	-0.017	0.1	-10000	0	-0.3	57	57
HB-EGF/EGFR	-0.035	0.11	-10000	0	-0.26	84	84
HBEGF	-0.033	0.09	-10000	0	-0.29	48	48
mol:DAG	-0.008	0.066	0.2	15	-0.29	10	25
cAMP biosynthetic process	-0.016	0.14	0.3	10	-0.34	59	69
NFKB1	0.026	0.004	-10000	0	-10000	0	0
SRC	0.025	0.005	-10000	0	-10000	0	0
GNB1	0.022	0.01	-10000	0	-10000	0	0
LYN	-0.015	0.12	0.24	19	-0.36	31	50
GNAQ	0.002	0.037	-10000	0	-0.25	7	7
LPAR2	0.018	0.054	-10000	0	-0.34	10	10
LPAR3	-0.009	0.043	-10000	0	-10000	0	0
LPAR1	-0.025	0.14	-10000	0	-0.39	57	57
IL8	-0.1	0.21	0.33	11	-0.44	110	121
PTK2	-0.014	0.09	0.19	25	-0.22	60	85
Rac1/GDP	0.017	0.007	-10000	0	-10000	0	0
CASP3	-0.021	0.087	-10000	0	-0.27	52	52
EGFR	-0.017	0.12	-10000	0	-0.4	46	46
PLCG1	-0.013	0.059	0.15	6	-0.22	23	29
PLD2	-0.013	0.094	0.19	29	-0.22	63	92
G12/G13	0.018	0.084	-10000	0	-0.23	48	48
PI3K-beta	-0.022	0.085	-10000	0	-0.27	30	30
cell migration	0.009	0.052	0.24	1	-0.24	5	6
SLC9A3R2	0.025	0.01	-10000	0	-0.13	2	2
PXN	0.002	0.098	0.2	8	-0.33	11	19
HRAS/GTP	-0.02	0.12	-10000	0	-0.33	60	60
RAC1	0.023	0.009	-10000	0	-10000	0	0
MMP9	-0.042	0.13	-10000	0	-0.23	133	133
PRKCE	0.022	0.034	-10000	0	-0.2	9	9
PRKCD	-0.009	0.096	0.22	30	-0.29	27	57
Gi(beta/gamma)	-0.019	0.13	-10000	0	-0.35	59	59
mol:LPA	-0.001	0.022	-10000	0	-0.16	9	9
TRIP6/p130 Cas/FAK1/Paxillin	-0.006	0.094	0.33	1	-0.35	9	10
MAPKKK cascade	-0.02	0.12	-10000	0	-0.32	60	60
contractile ring contraction involved in cytokinesis	0.001	0.087	0.22	21	-0.35	9	30
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.007	0.06	0.12	1	-0.26	23	24
GNA15	-0.005	0.057	-10000	0	-0.27	19	19
GNA12	0.022	0.009	-10000	0	-10000	0	0
GNA13	0.025	0.005	-10000	0	-10000	0	0
MAPT	-0.008	0.09	0.21	8	-0.27	20	28
GNA11	-0.002	0.049	-10000	0	-0.25	15	15
Rac1/GTP	0.03	0.11	-10000	0	-0.9	7	7
MMP2	-0.023	0.11	-10000	0	-0.3	57	57

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.006	0.085	0.19	4	-0.21	52	56
NF kappa B1 p50/RelA/I kappa B alpha	0.003	0.092	0.3	5	-0.27	10	15
alphaV/beta3 Integrin/Osteopontin/Src	0.002	0.095	-10000	0	-0.3	39	39
AP1	-0.023	0.12	-10000	0	-0.36	24	24
ILK	-0.015	0.08	-10000	0	-0.22	47	47
bone resorption	-0.032	0.13	0.32	2	-0.35	43	45
PTK2B	0.018	0.032	-10000	0	-0.13	22	22
PYK2/p130Cas	0.02	0.11	-10000	0	-0.25	55	55
ITGAV	0.027	0.011	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.005	0.11	-10000	0	-0.31	53	53
alphaV/beta3 Integrin/Osteopontin	0.018	0.1	-10000	0	-0.24	55	55
MAP3K1	-0.018	0.083	0.19	6	-0.22	51	57
JUN	0.019	0.023	-10000	0	-0.13	9	9
MAPK3	-0.026	0.081	0.19	4	-0.21	62	66
MAPK1	-0.026	0.079	0.19	3	-0.21	61	64
Rac1/GDP	0.017	0.007	-10000	0	-10000	0	0
NFKB1	0.026	0.004	-10000	0	-10000	0	0
MAPK8	-0.029	0.084	0.19	4	-0.23	54	58
ITGB3	0	0.082	-10000	0	-0.19	64	64
NFKBIA	-0.025	0.08	0.19	2	-0.27	15	17
FOS	-0.031	0.14	-10000	0	-0.33	72	72
CD44	-0.015	0.12	-10000	0	-0.31	62	62
CHUK	0.025	0.005	-10000	0	-10000	0	0
PLAU	-0.044	0.18	-10000	0	-1.1	12	12
NF kappa B1 p50/RelA	0.004	0.098	-10000	0	-0.34	11	11
BCAR1	0.025	0.02	-10000	0	-0.43	1	1
RELA	0.025	0.005	-10000	0	-10000	0	0
alphaV beta3 Integrin	0.02	0.064	-10000	0	-0.3	12	12
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	-0.025	0.1	0.19	7	-0.27	57	64
VAV3	-0.05	0.098	0.19	4	-0.24	79	83
MAP3K14	-0.019	0.084	0.19	4	-0.22	52	56
ROCK2	0.008	0.088	-10000	0	-0.43	20	20
SPP1	-0.023	0.12	-10000	0	-0.31	65	65
RAC1	0.023	0.009	-10000	0	-10000	0	0
Rac1/GTP	-0.035	0.092	0.18	3	-0.23	60	63
MMP2	-0.046	0.11	-10000	0	-0.4	24	24

×

Nongenotropic Androgen 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
PTK2	0.006	0.003	-10000	0	-10000	0	0
GNB1/GNG2	0.004	0.097	-10000	0	-0.22	75	75
regulation of S phase of mitotic cell cycle	-0.01	0.083	-10000	0	-0.22	69	69
GNAO1	0.022	0.045	-10000	0	-0.43	5	5
HRAS	0.024	0.006	-10000	0	-10000	0	0
SHBG/T-DHT	0.012	0.036	-10000	0	-0.25	9	9
PELP1	0.026	0.002	-10000	0	-10000	0	0
AKT1	0.007	0.001	-10000	0	-10000	0	0
MAP2K1	-0.035	0.096	0.18	27	-0.29	18	45
T-DHT/AR	-0.033	0.11	-10000	0	-0.23	104	104
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.002	-10000	0	-0.007	55	55
GNAI2	0.025	0.005	-10000	0	-10000	0	0
GNAI3	0.021	0.01	-10000	0	-10000	0	0
GNAI1	0.019	0.036	-10000	0	-0.43	3	3
mol:GDP	-0.05	0.13	-10000	0	-0.38	71	71
cell proliferation	-0.043	0.16	0.29	7	-0.42	53	60
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
FOS	-0.075	0.26	0.27	1	-0.78	56	57
mol:Ca2+	-0.007	0.019	-10000	0	-0.054	50	50
MAPK3	-0.036	0.13	0.27	8	-0.32	51	59
MAPK1	-0.015	0.089	0.22	1	-0.3	17	18
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
mol:IP3	0	0.001	-10000	0	-0.004	55	55
cAMP biosynthetic process	-0.001	0.036	0.23	1	-0.24	9	10
GNG2	0.022	0.04	-10000	0	-0.43	4	4
potassium channel inhibitor activity	0	0.001	-10000	0	-0.004	55	55
HRAS/GTP	0	0.095	-10000	0	-0.22	70	70
actin cytoskeleton reorganization	0.029	0.019	-10000	0	-10000	0	0
SRC	0.025	0.005	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.004	55	55
PI3K	0.035	0.007	-10000	0	-10000	0	0
apoptosis	0.033	0.15	0.42	55	-0.24	6	61
T-DHT/AR/PELP1	-0.014	0.1	-10000	0	-0.26	71	71
HRAS/GDP	-0.036	0.13	-10000	0	-0.36	71	71
CREB1	-0.037	0.16	0.25	6	-0.45	55	61
RAC1-CDC42/GTP	0.036	0.024	-10000	0	-10000	0	0
AR	-0.048	0.16	-10000	0	-0.34	104	104
GNB1	0.022	0.01	-10000	0	-10000	0	0
RAF1	-0.02	0.098	0.19	15	-0.22	69	84
RAC1-CDC42/GDP	-0.021	0.13	-10000	0	-0.34	67	67
T-DHT/AR/PELP1/Src	0.006	0.099	-10000	0	-0.24	71	71
MAP2K2	-0.036	0.092	0.18	23	-0.29	16	39
T-DHT/AR/PELP1/Src/PI3K	-0.011	0.084	-10000	0	-0.22	69	69
GNAZ	0.026	0.004	-10000	0	-10000	0	0
SHBG	0.017	0.06	-10000	0	-0.43	9	9
Gi family/GNB1/GNG2/GDP	-0.03	0.12	-10000	0	-0.35	37	37
mol:T-DHT	0	0.001	-10000	0	-0.002	36	36
RAC1	0.023	0.009	-10000	0	-10000	0	0
GNRH1	0.002	0.035	-10000	0	-0.3	6	6
Gi family/GTP	-0.021	0.068	-10000	0	-0.2	37	37
CDC42	0.022	0.01	-10000	0	-10000	0	0

×

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

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
MET/RANBP9	-0.022	0.1	-10000	0	-0.3	52	52
CRKL	0.011	0.14	0.29	9	-0.46	20	29
mol:PIP3	0.001	0.039	-10000	0	-0.84	1	1
AKT1	-0.003	0.043	0.28	1	-0.73	1	2
PTK2B	0.018	0.032	-10000	0	-0.13	22	22
RAPGEF1	0.014	0.14	0.3	12	-0.44	20	32
RANBP10	0.026	0.002	-10000	0	-10000	0	0
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
HGF/MET/SHIP2	-0.004	0.11	-10000	0	-0.24	81	81
MAP3K5	-0.008	0.16	0.28	11	-0.47	29	40
HGF/MET/CIN85/CBL/ENDOPHILINS	0.007	0.11	-10000	0	-0.26	55	55
AP1	-0.01	0.1	0.15	4	-0.24	55	59
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.024	0.014	-10000	0	-10000	0	0
apoptosis	-0.17	0.38	-10000	0	-0.8	130	130
STAT3 (dimer)	-0.006	0.09	0.22	4	-0.41	7	11
GAB1/CRKL/SHP2/PI3K	0.038	0.14	0.29	5	-0.43	19	24
INPP5D	0.022	0.037	-10000	0	-0.28	6	6
CBL/CRK	0.02	0.14	0.29	8	-0.44	20	28
PTPN11	0.026	0.003	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.025	0.005	-10000	0	-10000	0	0
PTEN	0.025	0.006	-10000	0	-10000	0	0
ELK1	0.038	0.16	0.31	119	-0.27	2	121
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.007	0.066	-10000	0	-0.3	12	12
PAK1	-0.004	0.059	-10000	0	-0.7	1	1
HGF/MET/RANBP10	-0.004	0.11	-10000	0	-0.24	83	83
HRAS	-0.047	0.2	-10000	0	-0.6	53	53
DOCK1	0.008	0.14	0.28	10	-0.44	20	30
GAB1	0	0.14	0.26	2	-0.49	19	21
CRK	0.01	0.14	0.3	10	-0.46	20	30
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.045	0.19	-10000	0	-0.53	63	63
JUN	0.019	0.023	-10000	0	-0.13	9	9
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.026	0.082	-10000	0	-0.24	60	60
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
cell morphogenesis	0.019	0.14	0.31	29	-0.45	11	40
GRB2/SHC	0.005	0.088	0.19	8	-0.22	51	59
FOS	-0.031	0.14	-10000	0	-0.43	48	48
GLMN	0.003	0.002	-10000	0	-10000	0	0
cell motility	0.037	0.16	0.31	119	-0.27	2	121
HGF/MET/MUC20	-0.032	0.1	-10000	0	-0.24	83	83
cell migration	0.005	0.087	0.19	8	-0.22	51	59
GRB2	0.025	0.006	-10000	0	-10000	0	0
CBL	0.025	0.007	-10000	0	-10000	0	0
MET/RANBP10	-0.022	0.1	-10000	0	-0.3	52	52
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.014	0.084	-10000	0	-0.24	53	53
MET/MUC20	-0.031	0.097	-10000	0	-0.3	52	52
RAP1B	0.015	0.14	0.3	15	-0.41	20	35
RAP1A	0.013	0.13	0.3	14	-0.4	20	34
HGF/MET/RANBP9	-0.004	0.11	-10000	0	-0.24	83	83
RAF1	-0.024	0.2	0.35	2	-0.56	53	55
STAT3	-0.006	0.09	0.22	4	-0.41	7	11
cell proliferation	0.001	0.15	0.3	13	-0.36	54	67
RPS6KB1	-0.005	0.043	-10000	0	-0.17	17	17
MAPK3	0.025	0.15	0.52	7	-10000	0	7
MAPK1	0.031	0.16	0.58	12	-10000	0	12
RANBP9	0.026	0.003	-10000	0	-10000	0	0
MAPK8	-0.01	0.15	0.3	6	-0.46	26	32
SRC	-0.018	0.078	0.16	1	-0.23	53	54
PI3K	0.005	0.09	0.19	9	-0.22	59	68
MET/Glomulin	-0.038	0.092	-10000	0	-0.28	52	52
SOS1	0.026	0.002	-10000	0	-10000	0	0
MAP2K1	-0.021	0.19	0.33	4	-0.52	53	57
MET	-0.047	0.14	-10000	0	-0.43	52	52
MAP4K1	-0.006	0.17	0.28	12	-0.48	29	41
PTK2	0.023	0.008	-10000	0	-10000	0	0
MAP2K2	-0.015	0.2	0.33	17	-0.52	53	70
BAD	0	0.051	-10000	0	-0.7	1	1
MAP2K4	-0.006	0.15	0.29	11	-0.43	28	39
SHP2/GRB2/SOS1/GAB1	-0.006	0.13	-10000	0	-0.35	51	51
INPPL1	0.025	0.005	-10000	0	-10000	0	0
PXN	0.026	0.004	-10000	0	-10000	0	0
SH3KBP1	0.026	0.003	-10000	0	-10000	0	0
HGS	-0.025	0.074	0.17	2	-0.22	57	59
PLCgamma1/PKC	0.019	0.004	-10000	0	-10000	0	0
HGF	-0.009	0.091	-10000	0	-0.2	69	69
RASA1	0.026	0.003	-10000	0	-10000	0	0
NCK1	0.025	0.02	-10000	0	-0.43	1	1
PTPRJ	0.025	0.005	-10000	0	-10000	0	0
NCK/PLCgamma1	0.005	0.094	0.19	10	-0.22	62	72
PDPK1	-0.002	0.045	0.32	1	-0.78	1	2
HGF/MET/SHIP	-0.007	0.11	-10000	0	-0.24	86	86

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.028	0.14	-10000	0	-0.41	55	55
PDGF/PDGFRA/CRKL	-0.003	0.099	-10000	0	-0.3	50	50
positive regulation of JUN kinase activity	0.03	0.084	-10000	0	-0.23	46	46
CRKL	0.026	0.008	-10000	0	-0.13	1	1
PDGF/PDGFRA/Caveolin-3	-0.009	0.1	-10000	0	-0.3	52	52
AP1	-0.094	0.25	-10000	0	-0.79	54	54
mol:IP3	-0.024	0.091	-10000	0	-0.31	44	44
PLCG1	-0.024	0.092	-10000	0	-0.31	44	44
PDGF/PDGFRA/alphaV Integrin	-0.003	0.1	-10000	0	-0.3	51	51
RAPGEF1	0.025	0.005	-10000	0	-10000	0	0
CRK	0.026	0.002	-10000	0	-10000	0	0
mol:Ca2+	-0.024	0.091	-10000	0	-0.31	44	44
CAV3	0.002	0.031	-10000	0	-0.13	14	14
CAV1	0.006	0.051	-10000	0	-0.43	2	2
SHC/Grb2/SOS1	0.032	0.085	-10000	0	-0.23	46	46
PDGF/PDGFRA/Shf	-0.005	0.11	-10000	0	-0.31	53	53
FOS	-0.1	0.25	0.31	2	-0.78	54	56
JUN	-0.02	0.025	0.16	1	-10000	0	1
oligodendrocyte development	-0.003	0.1	-10000	0	-0.3	51	51
GRB2	0.025	0.006	-10000	0	-10000	0	0
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
mol:DAG	-0.024	0.091	-10000	0	-0.31	44	44
PDGF/PDGFRA	-0.028	0.14	-10000	0	-0.41	55	55
actin cytoskeleton reorganization	-0.003	0.099	-10000	0	-0.29	51	51
SRF	0.014	0.011	-10000	0	-10000	0	0
SHC1	0.024	0.014	-10000	0	-10000	0	0
PI3K	0.019	0.088	-10000	0	-0.25	48	48
PDGF/PDGFRA/Crk/C3G	0.017	0.09	-10000	0	-0.25	51	51
JAK1	-0.021	0.088	-10000	0	-0.3	46	46
ELK1/SRF	-0.011	0.081	0.15	28	-0.25	41	69
SHB	0.026	0.004	-10000	0	-10000	0	0
SHF	0.022	0.04	-10000	0	-0.43	4	4
CSNK2A1	0.029	0.018	-10000	0	-10000	0	0
GO:0007205	-0.028	0.1	0.23	6	-0.34	43	49
SOS1	0.026	0.002	-10000	0	-10000	0	0
Ras protein signal transduction	0.03	0.084	-10000	0	-0.23	46	46
PDGF/PDGFRA/SHB	-0.003	0.099	-10000	0	-0.29	51	51
PDGF/PDGFRA/Caveolin-1	-0.005	0.085	-10000	0	-0.31	31	31
ITGAV	0.026	0.002	-10000	0	-10000	0	0
ELK1	-0.034	0.087	0.2	5	-0.3	43	48
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
PDGF/PDGFRA/Crk	-0.003	0.1	-10000	0	-0.3	51	51
JAK-STAT cascade	-0.021	0.088	-10000	0	-0.3	46	46
cell proliferation	-0.005	0.11	-10000	0	-0.31	53	53

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.025	0.005	-10000	0	-10000	0	0
VLDLR	0.014	0.067	-10000	0	-0.35	15	15
LRPAP1	0.026	0.005	-10000	0	-10000	0	0
NUDC	0.022	0.01	-10000	0	-10000	0	0
RELN/LRP8	0.003	0.095	-10000	0	-0.25	57	57
CaM/Ca2+	0.018	0.006	-10000	0	-10000	0	0
KATNA1	0.025	0.005	-10000	0	-10000	0	0
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	0.007	0.11	0.18	82	-0.23	53	135
IQGAP1/CaM	0.033	0.033	-10000	0	-0.28	4	4
DAB1	-0.039	0.15	-10000	0	-0.36	80	80
IQGAP1	0.02	0.043	-10000	0	-0.25	10	10
PLA2G7	-0.004	0.11	-10000	0	-0.31	46	46
CALM1	0.025	0.009	-10000	0	-0.13	1	1
DYNLT1	0.024	0.029	-10000	0	-0.43	2	2
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	0.03	0.026	-10000	0	-0.3	2	2
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0.026	0.004	-10000	0	-10000	0	0
CDK5R1	0	0.1	-10000	0	-0.42	30	30
LIS1/Poliovirus Protein 3A	0.01	0.002	-10000	0	-10000	0	0
CDK5R2	-0.05	0.16	-10000	0	-0.36	102	102
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.035	0.13	-10000	0	-0.27	109	109
YWHAE	0.026	0.002	-10000	0	-10000	0	0
NDEL1/14-3-3 E	0.014	0.18	0.32	79	-0.42	31	110
MAP1B	0.005	0.012	-10000	0	-0.26	1	1
RAC1	0.011	0.016	-10000	0	-10000	0	0
p35/CDK5	-0.021	0.092	0.18	8	-0.23	66	74
RELN	-0.046	0.14	-10000	0	-0.43	58	58
PAFAH/LIS1	0.011	0.064	0.17	1	-0.26	25	26
LIS1/CLIP170	0.028	0.007	-10000	0	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.03	0.11	-10000	0	-0.36	28	28
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.073	0.16	-10000	0	-0.3	132	132
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	-0.037	0.14	0.29	19	-0.43	32	51
LIS1/IQGAP1	0.025	0.029	0.17	2	-0.26	4	6
RHOA	0.012	0.016	-10000	0	-0.15	4	4
PAFAH1B1	0.013	0.003	-10000	0	-10000	0	0
PAFAH1B3	0.022	0.01	-10000	0	-10000	0	0
PAFAH1B2	0.012	0.074	-10000	0	-0.43	14	14
MAP1B/LIS1/Dynein heavy chain	0.025	0.019	-10000	0	-0.17	1	1
NDEL1/Katanin 60/Dynein heavy chain	0.019	0.18	0.32	78	-0.4	31	109
LRP8	0.02	0.03	-10000	0	-0.43	2	2
NDEL1/Katanin 60	0.013	0.18	0.32	80	-0.42	31	111
P39/CDK5	-0.037	0.11	0.21	11	-0.26	72	83
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.024	0.012	-10000	0	-10000	0	0
CDK5	-0.029	0.072	0.18	9	-0.22	52	61
PPP2R5D	0.026	0.002	-10000	0	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.024	0.006	-10000	0	-10000	0	0
CSNK2A1	0.025	0.005	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.024	0.12	-10000	0	-0.24	100	100
RELN/VLDLR	0.005	0.097	-10000	0	-0.23	66	66
CDC42	0.008	0.042	-10000	0	-0.46	4	4

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	0.047	0.025	-10000	0	-0.26	2	2
fibroblast growth factor receptor signaling pathway	0.046	0.027	-10000	0	-0.26	2	2
LAMA1	-0.024	0.14	-10000	0	-0.43	51	51
PRNP	0.025	0.005	-10000	0	-10000	0	0
GPC1/SLIT2	-0.016	0.11	-10000	0	-0.3	56	56
SMAD2	0.018	0.032	0.18	14	-0.23	1	15
GPC1/PrPc/Cu2+	0.032	0.013	-10000	0	-10000	0	0
GPC1/Laminin alpha1	-0.001	0.1	-10000	0	-0.3	51	51
TDGF1	-0.029	0.14	-10000	0	-0.34	75	75
CRIPTO/GPC1	-0.005	0.11	-10000	0	-0.31	54	54
APP/GPC1	0.036	0.014	-10000	0	-10000	0	0
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.018	0.088	-10000	0	-0.27	53	53
FLT1	0.024	0.021	-10000	0	-0.43	1	1
GPC1/TGFB/TGFBR1/TGFBR2	0.048	0.022	-10000	0	-0.2	2	2
SERPINC1	0.015	0.029	-10000	0	-0.13	14	14
FYN	-0.016	0.083	-10000	0	-0.26	51	51
FGR	-0.013	0.076	-10000	0	-0.26	42	42
positive regulation of MAPKKK cascade	-0.051	0.15	0.32	5	-0.4	55	60
SLIT2	-0.044	0.14	-10000	0	-0.27	122	122
GPC1/NRG	-0.043	0.13	-10000	0	-0.3	99	99
NRG1	-0.08	0.18	-10000	0	-0.32	156	156
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.05	0.018	-10000	0	-10000	0	0
LYN	-0.019	0.087	-10000	0	-0.26	54	54
mol:Spermine	0.006	0.008	-10000	0	-10000	0	0
cell growth	0.046	0.027	-10000	0	-0.26	2	2
BMP signaling pathway	-0.024	0.015	-10000	0	-10000	0	0
SRC	-0.014	0.081	-10000	0	-0.26	48	48
TGFBR1	0.024	0.022	-10000	0	-0.28	2	2
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.032	0.087	-10000	0	-0.19	84	84
GPC1	0.024	0.015	-10000	0	-10000	0	0
TGFBR1 (dimer)	0.024	0.022	-10000	0	-0.28	2	2
VEGFA	0.019	0.032	-10000	0	-0.13	22	22
BLK	-0.048	0.11	-10000	0	-0.28	76	76
HCK	-0.021	0.092	-10000	0	-0.28	53	53
FGF2	0.024	0.029	-10000	0	-0.43	2	2
FGFR1	0.025	0.005	-10000	0	-10000	0	0
VEGFR1 homodimer	0.024	0.021	-10000	0	-0.43	1	1
TGFBR2	0.024	0.016	-10000	0	-0.13	5	5
cell death	0.036	0.014	-10000	0	-10000	0	0
ATIII/GPC1	0.032	0.023	-10000	0	-10000	0	0
PLA2G2A/GPC1	0	0.07	-10000	0	-0.28	20	20
LCK	-0.037	0.1	-10000	0	-0.28	69	69
neuron differentiation	-0.043	0.13	-10000	0	-0.3	99	99
PrPc/Cu2+	0.019	0.004	-10000	0	-10000	0	0
APP	0.026	0.004	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.024	0.016	-10000	0	-0.13	5	5

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.026	0.008	-10000	0	-10000	0	0
LAT2	-0.023	0.12	0.17	4	-0.44	24	28
AP1	-0.015	0.17	-10000	0	-0.56	28	28
mol:PIP3	-0.009	0.17	0.3	37	-0.48	28	65
IKBKB	0.005	0.11	0.24	38	-0.27	20	58
AKT1	-0.03	0.11	0.31	22	-0.34	9	31
IKBKG	0.001	0.1	0.23	28	-0.27	20	48
MS4A2	-0.006	0.037	-10000	0	-0.14	24	24
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
MAP3K1	-0.007	0.13	0.32	10	-0.48	23	33
mol:Ca2+	-0.001	0.14	0.27	38	-0.37	25	63
LYN	0.021	0.036	-10000	0	-0.45	2	2
CBLB	-0.019	0.1	-10000	0	-0.4	21	21
SHC1	0.024	0.014	-10000	0	-10000	0	0
RasGAP/p62DOK	0.042	0.047	-10000	0	-0.23	14	14
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	0.022	0.037	-10000	0	-0.28	6	6
PLD2	-0.041	0.1	0.26	18	-0.24	73	91
PTPN13	-0.007	0.13	-10000	0	-0.54	16	16
PTPN11	0.021	0.02	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	-0.005	0.1	0.26	22	-0.31	15	37
SYK	0.009	0.085	-10000	0	-0.38	21	21
GRB2	0.025	0.006	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.029	0.14	0.21	6	-0.48	28	34
LAT	-0.029	0.11	-10000	0	-0.37	29	29
PAK2	-0.009	0.15	0.3	9	-0.54	23	32
NFATC2	-0.051	0.15	-10000	0	-0.53	43	43
HRAS	-0.014	0.16	0.26	8	-0.6	23	31
GAB2	0.025	0.005	-10000	0	-10000	0	0
PLA2G1B	0.025	0.094	-10000	0	-0.82	5	5
Fc epsilon R1	-0.016	0.13	-10000	0	-0.28	86	86
Antigen/IgE/Fc epsilon R1	-0.008	0.12	-10000	0	-0.25	86	86
mol:GDP	-0.016	0.16	0.25	3	-0.61	26	29
JUN	0.019	0.023	-10000	0	-0.13	9	9
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
FOS	-0.031	0.14	-10000	0	-0.43	48	48
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.017	0.11	-10000	0	-0.38	25	25
CHUK	0	0.1	0.22	31	-0.27	21	52
KLRG1	-0.023	0.098	0.16	3	-0.34	25	28
VAV1	-0.026	0.13	0.17	2	-0.47	26	28
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.018	0.1	0.18	4	-0.4	21	25
negative regulation of mast cell degranulation	-0.003	0.11	0.19	15	-0.42	17	32
BTK	-0.022	0.17	-10000	0	-0.68	25	25
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.051	0.14	-10000	0	-0.29	110	110
GAB2/PI3K/SHP2	-0.046	0.081	-10000	0	-0.24	61	61
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.024	0.11	0.19	1	-0.26	75	76
RAF1	0.02	0.099	-10000	0	-0.93	5	5
Fc epsilon R1/FcgammaRIIB/SHIP	-0.02	0.16	-10000	0	-0.28	122	122
FCER1G	0.006	0.09	-10000	0	-0.44	19	19
FCER1A	-0.06	0.15	-10000	0	-0.28	137	137
Antigen/IgE/Fc epsilon R1/Fyn	0.008	0.11	-10000	0	-0.24	76	76
MAPK3	0.024	0.093	-10000	0	-0.82	5	5
MAPK1	0.023	0.096	-10000	0	-0.85	5	5
NFKB1	0.026	0.004	-10000	0	-10000	0	0
MAPK8	0.003	0.14	-10000	0	-0.54	25	25
DUSP1	0.008	0.077	-10000	0	-0.25	32	32
NF-kappa-B/RelA	0.004	0.059	0.13	15	-0.17	16	31
actin cytoskeleton reorganization	-0.005	0.13	-10000	0	-0.53	16	16
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	0.006	0.14	0.26	3	-0.54	22	25
FER	-0.026	0.11	-10000	0	-0.34	36	36
RELA	0.025	0.005	-10000	0	-10000	0	0
ITK	-0.024	0.092	-10000	0	-0.35	35	35
SOS1	0.026	0.002	-10000	0	-10000	0	0
PLCG1	-0.007	0.17	0.29	17	-0.64	23	40
cytokine secretion	-0.002	0.038	-10000	0	-0.15	4	4
SPHK1	-0.028	0.12	0.2	1	-0.42	25	26
PTK2	-0.006	0.13	-10000	0	-0.58	13	13
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.017	0.15	0.25	10	-0.53	26	36
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	-0.004	0.16	0.3	30	-0.5	23	53
MAP2K2	0.023	0.098	-10000	0	-0.82	5	5
MAP2K1	0.015	0.092	-10000	0	-0.87	5	5
MAP2K7	0.025	0.005	-10000	0	-10000	0	0
KLRG1/SHP2	-0.007	0.1	0.18	21	-0.34	20	41
MAP2K4	0.032	0.063	-10000	0	-1.4	1	1
Fc epsilon R1/FcgammaRIIB	-0.031	0.16	-10000	0	-0.29	121	121
mol:Choline	-0.041	0.1	0.26	18	-0.23	73	91
SHC/Grb2/SOS1	0.019	0.12	-10000	0	-0.41	17	17
FYN	0.025	0.005	-10000	0	-10000	0	0
DOK1	0.025	0.021	-10000	0	-0.28	2	2
PXN	-0.004	0.12	-10000	0	-0.54	13	13
HCLS1	-0.026	0.12	-10000	0	-0.44	26	26
PRKCB	-0.005	0.13	0.26	28	-0.36	24	52
FCGR2B	-0.05	0.15	-10000	0	-0.26	135	135
IGHE	0	0.006	-10000	0	-10000	0	0
KLRG1/SHIP	-0.003	0.11	0.2	10	-0.42	17	27
LCP2	0.021	0.033	-10000	0	-0.15	14	14
PLA2G4A	-0.027	0.12	-10000	0	-0.38	34	34
RASA1	0.026	0.003	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.041	0.1	0.26	18	-0.23	73	91
IKK complex	0.009	0.092	0.22	39	-0.22	15	54
WIPF1	0.026	0.002	-10000	0	-10000	0	0

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.005	0.023	-10000	0	-0.3	1	1
MAP4K4	-0.01	0.094	-10000	0	-0.37	16	16
BAG4	0.014	0.071	-10000	0	-0.43	13	13
PKC zeta/ceramide	-0.032	0.13	0.14	1	-0.29	74	75
NFKBIA	0.026	0.004	-10000	0	-10000	0	0
BIRC3	-0.002	0.099	-10000	0	-0.3	42	42
BAX	-0.063	0.14	-10000	0	-0.35	93	93
RIPK1	0.026	0.003	-10000	0	-10000	0	0
AKT1	0.003	0.046	0.68	2	-10000	0	2
BAD	-0.036	0.12	0.19	12	-0.27	70	82
SMPD1	-0.009	0.076	0.16	7	-0.17	66	73
RB1	-0.041	0.12	0.18	1	-0.27	71	72
FADD/Caspase 8	-0.003	0.091	-10000	0	-0.38	13	13
MAP2K4	-0.04	0.11	0.24	1	-0.27	64	65
NSMAF	0.025	0.006	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.038	0.11	0.18	6	-0.32	43	49
EGF	-0.01	0.11	-10000	0	-0.43	33	33
mol:ceramide	-0.042	0.12	0.14	1	-0.28	73	74
MADD	0.025	0.005	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.007	0.024	-10000	0	-0.3	1	1
ASAH1	0.025	0.005	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.04	0.12	0.18	1	-0.26	71	72
cell proliferation	-0.02	0.11	-10000	0	-0.32	40	40
BID	-0.006	0.11	-10000	0	-0.64	7	7
MAP3K1	-0.041	0.12	0.25	1	-0.27	70	71
EIF2A	-0.04	0.11	0.25	2	-0.34	33	35
TRADD	0.025	0.02	-10000	0	-0.43	1	1
CRADD	0.026	0.003	-10000	0	-10000	0	0
MAPK3	-0.029	0.093	0.17	6	-0.43	16	22
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.03	0.093	0.17	6	-0.43	16	22
Cathepsin D/ceramide	-0.028	0.12	0.14	1	-0.27	71	72
FADD	-0.01	0.091	-10000	0	-0.36	15	15
KSR1	-0.041	0.12	-10000	0	-0.27	69	69
MAPK8	-0.068	0.16	-10000	0	-0.38	59	59
PRKRA	-0.041	0.12	0.13	1	-0.27	71	72
PDGFA	0.016	0.036	-10000	0	-0.43	1	1
TRAF2	0.026	0.005	-10000	0	-10000	0	0
IGF1	0.012	0.076	-10000	0	-0.34	20	20
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.042	0.12	0.14	1	-0.28	73	74
CTSD	0.025	0.006	-10000	0	-10000	0	0
regulation of nitric oxide biosynthetic process	0.037	0.009	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.021	0.12	-10000	0	-0.34	40	40
PRKCD	0.003	0.1	-10000	0	-0.43	26	26
PRKCZ	0.007	0.076	-10000	0	-0.43	14	14
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.007	0.024	-10000	0	-0.3	1	1
RelA/NF kappa B1	0.037	0.009	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.003	0.087	-10000	0	-0.25	44	44
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.013	0.096	-10000	0	-0.34	21	21
TNFR1A/BAG4/TNF-alpha	0	0.12	-10000	0	-0.27	77	77
mol:Sphingosine-1-phosphate	0.005	0.023	-10000	0	-0.3	1	1
MAP2K1	-0.037	0.11	0.18	6	-0.54	15	21
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.025	0.005	-10000	0	-10000	0	0
CYCS	-0.033	0.084	-10000	0	-0.21	82	82
TNFRSF1A	0.017	0.054	-10000	0	-0.34	10	10
NFKB1	0.026	0.004	-10000	0	-10000	0	0
TNFR1A/BAG4	0.023	0.063	-10000	0	-0.31	17	17
EIF2AK2	-0.041	0.11	0.16	3	-0.27	67	70
TNF-alpha/TNFR1A/FAN	0.008	0.11	-10000	0	-0.27	66	66
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.013	0.079	-10000	0	-0.51	6	6
MAP2K2	-0.032	0.088	0.17	6	-0.41	15	21
SMPD3	-0.02	0.1	0.19	1	-0.29	39	40
TNF	-0.06	0.16	-10000	0	-0.26	151	151
PKC zeta/PAR4	0.004	0.085	-10000	0	-0.31	31	31
mol:PHOSPHOCHOLINE	-0.009	0.089	0.2	33	-0.19	50	83
NF kappa B1/RelA/I kappa B alpha	0.045	0.073	-10000	0	-0.22	29	29
AIFM1	-0.044	0.095	-10000	0	-0.22	82	82
BCL2	0.021	0.045	-10000	0	-0.43	5	5

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.009	0.057	-10000	0	-0.25	22	22
NFATC2	-0.022	0.075	-10000	0	-0.26	40	40
NFATC3	0.002	0.023	-10000	0	-0.14	1	1
CD40LG	-0.073	0.14	0.31	3	-0.38	51	54
PTGS2	-0.094	0.18	0.36	1	-0.46	74	75
JUNB	0.007	0.072	-10000	0	-0.21	39	39
CaM/Ca2+/Calcineurin A alpha-beta B1	0.011	0.018	-10000	0	-10000	0	0
CaM/Ca2+	0.011	0.018	-10000	0	-10000	0	0
CALM1	0.021	0.016	-10000	0	-0.14	1	1
JUN	0.015	0.025	-10000	0	-0.14	9	9
mol:Ca2+	-0.003	0.006	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.016	0.005	-10000	0	-10000	0	0
FOSL1	-0.028	0.13	-10000	0	-0.25	97	97
CREM	0.023	0.022	-10000	0	-0.43	1	1
Jun/NFAT1-c-4/p21SNFT	-0.029	0.12	-10000	0	-0.35	34	34
FOS	-0.036	0.14	-10000	0	-0.37	62	62
IFNG	-0.072	0.14	0.31	1	-0.38	49	50
AP-1/NFAT1-c-4	-0.057	0.17	-10000	0	-0.42	50	50
FASLG	-0.073	0.14	0.36	1	-0.38	50	51
NFAT1-c-4/ICER1	-0.024	0.097	0.18	1	-0.25	56	57
IL2RA	-0.074	0.15	0.31	3	-0.39	55	58
FKBP12/FK506	0.019	0.004	-10000	0	-10000	0	0
CSF2	-0.072	0.14	0.33	2	-0.38	45	47
JunB/Fra1/NFAT1-c-4	-0.039	0.13	0.19	2	-0.27	90	92
IL4	-0.071	0.14	0.33	2	-0.38	46	48
IL2	-0.011	0.14	-10000	0	-0.93	12	12
IL3	0.009	0.069	-10000	0	-0.66	5	5
FKBP1A	0.025	0.005	-10000	0	-10000	0	0
BATF3	0.001	0.091	-10000	0	-0.26	45	45
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.025	0.02	-10000	0	-0.43	1	1

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.019	0.002	-10000	0	-10000	0	0
PRKCZ	0.007	0.076	-10000	0	-0.43	14	14
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.024	0.007	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.023	0.098	-10000	0	-0.32	34	34
IRAK/TOLLIP	0.028	0.008	-10000	0	-10000	0	0
IKBKB	0.025	0.005	-10000	0	-10000	0	0
IKBKG	0.026	0.003	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.056	0.14	-10000	0	-0.31	101	101
IL1A	-0.033	0.14	-10000	0	-0.28	97	97
IL1B	-0.057	0.12	-10000	0	-0.32	76	76
IRAK/TRAF6/p62/Atypical PKCs	0.045	0.052	-10000	0	-0.2	15	15
IL1R2	-0.045	0.14	-10000	0	-0.25	127	127
IL1R1	0.006	0.077	-10000	0	-0.43	12	12
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.026	0.093	-10000	0	-0.34	23	23
TOLLIP	0.025	0.006	-10000	0	-10000	0	0
TICAM2	0.016	0.064	-10000	0	-0.38	12	12
MAP3K3	0.025	0.005	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.017	0.003	-10000	0	-10000	0	0
IKK complex/ELKS	0.03	0.049	-10000	0	-10000	0	0
JUN	-0.009	0.036	0.16	6	-0.22	10	16
MAP3K7	0.026	0.004	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.017	0.12	-10000	0	-0.25	82	82
IL1 alpha/IL1R1/IL1RAP/MYD88	0.02	0.12	-10000	0	-0.26	66	66
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.029	0.12	-10000	0	-0.24	66	66
IL1 beta fragment/IL1R1/IL1RAP	-0.044	0.12	0.17	1	-0.26	90	91
NFKB1	0.026	0.004	-10000	0	-10000	0	0
MAPK8	-0.009	0.042	0.17	10	-0.21	13	23
IRAK1	0.014	0.002	-10000	0	-10000	0	0
IL1RN/IL1R1	-0.022	0.12	-10000	0	-0.28	69	69
IRAK4	0.026	0.004	-10000	0	-10000	0	0
PRKCI	0.026	0.003	-10000	0	-10000	0	0
TRAF6	0.024	0.021	-10000	0	-0.43	1	1
PI3K	0.038	0.007	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.025	0.11	-10000	0	-0.36	30	30
CHUK	0.025	0.005	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.044	0.12	0.17	1	-0.26	90	91
IL1 beta/IL1R2	-0.073	0.14	-10000	0	-0.26	144	144
IRAK/TRAF6/TAK1/TAB1/TAB2	0.035	0.015	-10000	0	-0.2	1	1
NF kappa B1 p50/RelA	-0.023	0.11	-10000	0	-0.35	18	18
IRAK3	0.022	0.041	-10000	0	-0.33	6	6
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.023	0.13	-10000	0	-0.26	89	89
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.012	0.099	-10000	0	-0.25	65	65
IL1 alpha/IL1R1/IL1RAP	0.009	0.11	-10000	0	-0.28	62	62
RELA	0.025	0.005	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.026	0.004	-10000	0	-10000	0	0
MYD88	0.019	0.054	-10000	0	-0.43	7	7
IRAK/TRAF6/MEKK3	0.042	0.018	-10000	0	-0.22	1	1
IL1RAP	0.007	0.067	-10000	0	-0.43	7	7
UBE2N	0.026	0.003	-10000	0	-10000	0	0
IRAK/TRAF6	-0.04	0.1	-10000	0	-0.32	28	28
CASP1	0.01	0.071	-10000	0	-0.43	11	11
IL1RN/IL1R2	-0.056	0.14	-10000	0	-0.29	114	114
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.028	0.13	-10000	0	-0.26	87	87
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.012	0.1	-10000	0	-0.36	28	28
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
IL1RN	-0.035	0.13	-10000	0	-0.24	117	117
TRAF6/TAK1/TAB1/TAB2	0.036	0.015	-10000	0	-0.21	1	1
MAP2K6	0.015	0.028	0.18	11	-0.2	2	13

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.06	0.25	-10000	0	-0.85	38	38
NCK1/PAK1/Dok-R	-0.056	0.12	-10000	0	-0.41	39	39
NCK1/Dok-R	-0.057	0.28	-10000	0	-1	36	36
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
mol:beta2-estradiol	0.011	0.058	0.23	31	-10000	0	31
RELA	0.025	0.005	-10000	0	-10000	0	0
SHC1	0.024	0.015	-10000	0	-10000	0	0
Rac/GDP	0.017	0.007	-10000	0	-10000	0	0
F2	0.012	0.064	0.25	27	-10000	0	27
TNIP2	0.025	0.005	-10000	0	-10000	0	0
NF kappa B/RelA	-0.03	0.27	-10000	0	-0.96	36	36
FN1	0.021	0.029	-10000	0	-10000	0	0
PLD2	-0.064	0.28	-10000	0	-1.1	36	36
PTPN11	0.026	0.003	-10000	0	-10000	0	0
GRB14	-0.071	0.16	-10000	0	-0.25	180	180
ELK1	-0.057	0.26	-10000	0	-0.95	36	36
GRB7	0.001	0.044	-10000	0	-0.13	41	41
PAK1	0.008	0.061	-10000	0	-0.43	5	5
Tie2/Ang1/alpha5/beta1 Integrin	-0.036	0.28	-10000	0	-0.99	36	36
CDKN1A	-0.069	0.24	-10000	0	-0.67	61	61
ITGA5	0.017	0.043	-10000	0	-0.16	24	24
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.057	0.28	-10000	0	-1	36	36
CRK	0.026	0.002	-10000	0	-10000	0	0
mol:NO	-0.01	0.21	-10000	0	-0.6	38	38
PLG	-0.068	0.28	-10000	0	-1.1	36	36
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.052	0.23	-10000	0	-0.81	37	37
GRB2	0.025	0.006	-10000	0	-10000	0	0
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
ANGPT2	-0.066	0.24	-10000	0	-0.87	31	31
BMX	-0.072	0.28	-10000	0	-1.1	36	36
ANGPT1	-0.083	0.3	-10000	0	-1.2	32	32
tube development	-0.063	0.22	-10000	0	-0.66	53	53
ANGPT4	-0.008	0.1	-10000	0	-0.27	53	53
response to hypoxia	-0.006	0.018	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.086	0.31	-10000	0	-1.2	36	36
alpha5/beta1 Integrin	0.029	0.034	-10000	0	-0.26	3	3
FGF2	0.024	0.03	-10000	0	-0.43	2	2
STAT5A (dimer)	-0.073	0.28	-10000	0	-0.73	66	66
mol:L-citrulline	-0.01	0.21	-10000	0	-0.6	38	38
AGTR1	0	0.094	-10000	0	-0.29	39	39
MAPK14	-0.059	0.28	-10000	0	-1	37	37
Tie2/SHP2	-0.019	0.2	-10000	0	-1.1	14	14
TEK	-0.022	0.21	-10000	0	-1.2	14	14
RPS6KB1	-0.047	0.24	-10000	0	-0.81	37	37
Angiotensin II/AT1	0	0.067	-10000	0	-0.24	30	30
Tie2/Ang1/GRB2	-0.056	0.29	-10000	0	-1.1	36	36
MAPK3	-0.061	0.26	-10000	0	-0.98	36	36
MAPK1	-0.061	0.26	-10000	0	-0.97	36	36
Tie2/Ang1/GRB7	-0.06	0.3	-10000	0	-1.1	36	36
NFKB1	0.026	0.004	-10000	0	-10000	0	0
MAPK8	-0.068	0.29	-10000	0	-1.1	36	36
PI3K	-0.063	0.28	-10000	0	-0.97	37	37
FES	-0.062	0.29	-10000	0	-1	37	37
Crk/Dok-R	-0.057	0.28	-10000	0	-1	36	36
Tie2/Ang1/ABIN2	-0.056	0.3	-10000	0	-1.1	36	36
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.052	0.23	-10000	0	-0.76	38	38
STAT5A	0.016	0.066	-10000	0	-0.43	11	11
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.038	0.25	-10000	0	-0.81	37	37
Tie2/Ang2	-0.087	0.3	-10000	0	-0.9	53	53
Tie2/Ang1	-0.065	0.3	-10000	0	-1.1	36	36
FOXO1	-0.059	0.24	-10000	0	-0.72	53	53
ELF1	0.026	0.022	-10000	0	-10000	0	0
ELF2	-0.06	0.28	-10000	0	-1	36	36
mol:Choline	-0.061	0.27	-10000	0	-1	36	36
cell migration	-0.029	0.066	-10000	0	-0.23	39	39
FYN	-0.074	0.25	-10000	0	-0.76	53	53
DOK2	-0.016	0.11	-10000	0	-0.25	77	77
negative regulation of cell cycle	-0.06	0.22	-10000	0	-0.59	66	66
ETS1	0.003	0.082	-10000	0	-0.28	35	35
PXN	-0.023	0.22	0.41	3	-0.67	37	40
ITGB1	0.023	0.012	-10000	0	-10000	0	0
NOS3	-0.02	0.23	-10000	0	-0.69	38	38
RAC1	0.023	0.009	-10000	0	-10000	0	0
TNF	-0.074	0.17	-10000	0	-0.41	91	91
MAPKKK cascade	-0.061	0.27	-10000	0	-1	36	36
RASA1	0.026	0.003	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.058	0.3	-10000	0	-1.1	36	36
NCK1	0.025	0.02	-10000	0	-0.43	1	1
vasculogenesis	-0.005	0.19	0.34	2	-0.54	38	40
mol:Phosphatidic acid	-0.061	0.27	-10000	0	-1	36	36
mol:Angiotensin II	-0.001	0.006	-10000	0	-10000	0	0
mol:NADP	-0.01	0.21	-10000	0	-0.6	38	38
Rac1/GTP	-0.044	0.22	-10000	0	-0.75	37	37
MMP2	-0.07	0.28	-10000	0	-1.1	36	36

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	0.034	0.1	-10000	0	-0.23	61	61
SMAD6-7/SMURF1	0.039	0.03	-10000	0	-0.26	2	2
NOG	-0.029	0.14	-10000	0	-0.39	67	67
SMAD9	-0.047	0.18	-10000	0	-0.49	61	61
SMAD4	0.026	0.004	-10000	0	-10000	0	0
SMAD5	-0.022	0.11	0.19	1	-0.39	22	23
BMP7/USAG1	-0.009	0.093	-10000	0	-0.3	37	37
SMAD5/SKI	-0.013	0.11	-10000	0	-0.37	24	24
SMAD1	0.019	0.05	-10000	0	-0.42	2	2
BMP2	-0.033	0.15	-10000	0	-0.43	66	66
SMAD1/SMAD1/SMAD4	0.022	0.053	-10000	0	-0.31	3	3
BMPR1A	0.025	0.005	-10000	0	-10000	0	0
BMPR1B	0.003	0.1	-10000	0	-0.43	26	26
BMPR1A-1B/BAMBI	0.031	0.069	-10000	0	-0.26	24	24
AHSG	-0.029	0.14	-10000	0	-0.43	49	49
CER1	-0.001	0.033	-10000	0	-10000	0	0
BMP2-4/CER1	-0.005	0.13	-10000	0	-0.31	69	69
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.033	0.13	-10000	0	-0.42	35	35
BMP2-4 (homodimer)	-0.017	0.14	-10000	0	-0.36	69	69
RGMB	0.02	0.047	-10000	0	-0.3	9	9
BMP6/BMPR2/BMPR1A-1B	0.044	0.074	-10000	0	-0.24	29	29
RGMA	0.016	0.066	-10000	0	-0.43	11	11
SMURF1	0.021	0.011	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.025	0.12	-10000	0	-0.39	38	38
BMP2-4/USAG1	-0.011	0.13	-10000	0	-0.3	82	82
SMAD6/SMURF1/SMAD5	-0.011	0.1	-10000	0	-0.38	20	20
SOSTDC1	-0.028	0.12	-10000	0	-0.23	102	102
BMP7/BMPR2/BMPR1A-1B	0.043	0.072	-10000	0	-0.23	30	30
SKI	0.022	0.01	-10000	0	-10000	0	0
BMP6 (homodimer)	0.017	0.054	-10000	0	-0.24	17	17
HFE2	0.012	0.025	-10000	0	-0.13	8	8
ZFYVE16	0.026	0.003	-10000	0	-10000	0	0
MAP3K7	0.026	0.004	-10000	0	-10000	0	0
BMP2-4/CHRD	-0.001	0.13	-10000	0	-0.3	72	72
SMAD5/SMAD5/SMAD4	-0.015	0.11	-10000	0	-0.36	26	26
MAPK1	0.026	0.003	-10000	0	-10000	0	0
TAK1/TAB family	-0.011	0.1	-10000	0	-0.36	24	24
BMP7 (homodimer)	0.02	0.049	-10000	0	-0.43	6	6
NUP214	0.025	0.005	-10000	0	-10000	0	0
BMP6/FETUA	-0.008	0.11	-10000	0	-0.32	52	52
SMAD1/SKI	0.025	0.057	-10000	0	-0.37	3	3
SMAD6	0.022	0.041	-10000	0	-0.43	4	4
CTDSP2	0.025	0.006	-10000	0	-10000	0	0
BMP2-4/FETUA	-0.023	0.15	-10000	0	-0.32	101	101
MAP3K7IP1	0	0	-10000	0	-10000	0	0
GREM1	-0.079	0.17	-10000	0	-0.3	162	162
BMPR2 (homodimer)	0.026	0.002	-10000	0	-10000	0	0
GADD34/PP1CA	0.042	0.023	-10000	0	-10000	0	0
BMPR1A-1B (homodimer)	0.02	0.074	-10000	0	-0.3	25	25
CHRDL1	-0.036	0.15	-10000	0	-0.43	65	65
ENDOFIN/SMAD1	0.03	0.06	0.3	1	-0.37	3	4
SMAD6-7/SMURF1/SMAD1	0.036	0.064	-10000	0	-0.35	4	4
SMAD6/SMURF1	0.021	0.011	-10000	0	-10000	0	0
BAMBI	0.022	0.019	-10000	0	-0.13	6	6
SMURF2	0.024	0.029	-10000	0	-0.43	2	2
BMP2-4/CHRDL1	-0.036	0.16	-10000	0	-0.3	125	125
BMP2-4/GREM1	-0.054	0.17	-10000	0	-0.3	153	153
SMAD7	0.026	0.004	-10000	0	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.038	0.18	-10000	0	-0.47	61	61
SMAD1/SMAD6	0.021	0.055	-10000	0	-0.36	3	3
TAK1/SMAD6	0.03	0.017	-10000	0	-10000	0	0
BMP7	0.02	0.049	-10000	0	-0.43	6	6
BMP6	0.017	0.054	-10000	0	-0.24	17	17
MAP3K7IP2	0	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.029	0.11	-10000	0	-0.35	37	37
PPM1A	0.025	0.005	-10000	0	-10000	0	0
SMAD1/SMURF2	0.029	0.061	0.3	1	-0.36	3	4
SMAD7/SMURF1	0.03	0.016	-10000	0	-10000	0	0
CTDSPL	0.025	0.02	-10000	0	-0.43	1	1
PPP1CA	0.025	0.005	-10000	0	-10000	0	0
XIAP	0.026	0.001	-10000	0	-10000	0	0
CTDSP1	0.026	0.003	-10000	0	-10000	0	0
PPP1R15A	0.019	0.021	-10000	0	-0.13	7	7
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.049	0.14	-10000	0	-0.42	46	46
CHRD	0.021	0.045	-10000	0	-0.43	5	5
BMPR2	0.026	0.002	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.032	0.13	-10000	0	-0.41	40	40
BMP4	0.007	0.088	-10000	0	-0.4	22	22
FST	-0.016	0.12	-10000	0	-0.27	71	71
BMP2-4/NOG	-0.024	0.17	-10000	0	-0.39	83	83
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	0.044	0.069	-10000	0	-0.22	25	25

×

PLK1 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0.023	0.076	0.22	66	-0.092	6	72
BUB1B	-0.03	0.1	0.12	2	-0.27	71	73
PLK1	0.003	0.031	0.093	11	-0.12	9	20
PLK1S1	0.007	0.029	0.11	3	-0.16	6	9
KIF2A	0	0.039	0.21	5	-0.19	6	11
regulation of mitotic centrosome separation	0.003	0.031	0.093	11	-0.12	9	20
GOLGA2	0.025	0.005	-10000	0	-10000	0	0
Hec1/SPC24	-0.034	0.14	-10000	0	-0.29	100	100
WEE1	-0.003	0.084	-10000	0	-0.35	25	25
cytokinesis	-0.067	0.16	0.23	1	-0.39	97	98
PP2A-alpha B56	-0.031	0.22	-10000	0	-0.63	62	62
AURKA	0.008	0.025	0.11	1	-0.34	1	2
PICH/PLK1	-0.008	0.062	0.16	6	-0.22	24	30
CENPE	-0.018	0.061	0.11	1	-0.24	28	29
RhoA/GTP	0.019	0.003	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.001	0.039	0.21	5	-0.18	6	11
PPP2CA	0.026	0.003	-10000	0	-10000	0	0
FZR1	0.025	0.006	-10000	0	-10000	0	0
TPX2	-0.006	0.071	0.11	11	-0.27	31	42
PAK1	0.009	0.061	-10000	0	-0.44	5	5
SPC24	-0.044	0.14	-10000	0	-0.43	55	55
FBXW11	0.026	0.004	-10000	0	-10000	0	0
CLSPN	-0.05	0.12	0.12	3	-0.26	119	122
GORASP1	0.026	0.004	-10000	0	-10000	0	0
metaphase	0	0.003	0.017	3	-0.017	5	8
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.001	0.017	0.051	15	-0.065	8	23
G2 phase of mitotic cell cycle	0	0.002	0.014	2	-0.01	1	3
STAG2	0.026	0.001	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.013	0.072	-10000	0	-0.52	9	9
spindle elongation	0.003	0.031	0.093	11	-0.12	9	20
ODF2	0.026	0.005	-10000	0	-10000	0	0
BUB1	-0.052	0.23	-10000	0	-0.68	61	61
TPT1	0	0.043	-10000	0	-0.18	22	22
CDC25C	-0.028	0.12	0.15	1	-0.36	56	57
CDC25B	0.026	0.006	-10000	0	-10000	0	0
SGOL1	-0.023	0.076	0.092	6	-0.22	66	72
RHOA	0.026	0.004	-10000	0	-10000	0	0
CCNB1/CDK1	0.03	0.041	-10000	0	-0.23	5	5
CDC14B	0.006	0.002	-10000	0	-10000	0	0
CDC20	-0.028	0.12	-10000	0	-0.25	93	93
PLK1/PBIP1	-0.013	0.06	0.087	1	-0.22	33	34
mitosis	-0.002	0.004	0.023	2	-10000	0	2
FBXO5	0	0.03	0.097	5	-0.14	6	11
CDC2	0.001	0.002	0.011	1	-0.014	1	2
NDC80	-0.056	0.16	-10000	0	-0.43	73	73
metaphase plate congression	-0.024	0.089	-10000	0	-0.23	76	76
ERCC6L	-0.003	0.063	0.26	1	-0.22	24	25
NLP/gamma Tubulin	0.003	0.02	0.069	8	-0.087	6	14
microtubule cytoskeleton organization	0	0.043	-10000	0	-0.18	22	22
G2/M transition DNA damage checkpoint	0	0.002	0.016	1	-10000	0	1
PPP1R12A	0.026	0.02	-10000	0	-0.43	1	1
interphase	0	0.002	0.016	1	-10000	0	1
PLK1/PRC1-2	-0.016	0.11	0.14	1	-0.22	97	98
GRASP65/GM130/RAB1/GTP/PLK1	0.037	0.035	-10000	0	-0.17	1	1
RAB1A	0.026	0.002	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.004	0.026	0.078	25	-0.13	3	28
mitotic prometaphase	0.002	0.007	0.018	76	-0.012	3	79
proteasomal ubiquitin-dependent protein catabolic process	0.005	0.06	0.21	1	-0.48	2	3
microtubule-based process	-0.032	0.1	0.12	2	-0.24	95	97
Golgi organization	0.003	0.031	0.093	11	-0.12	9	20
Cohesin/SA2	0.017	0.028	0.1	1	-0.12	5	6
PPP1CB/MYPT1	0.038	0.016	-10000	0	-0.31	1	1
KIF20A	-0.078	0.17	-10000	0	-0.43	93	93
APC/C/CDC20	-0.004	0.074	0.12	2	-0.23	40	42
PPP2R1A	0.022	0.01	-10000	0	-10000	0	0
chromosome segregation	-0.013	0.06	0.086	1	-0.22	33	34
PRC1	0.019	0.032	-10000	0	-0.13	21	21
ECT2	0.001	0.038	0.22	6	-0.17	3	9
C13orf34	0.003	0.026	0.073	22	-0.1	8	30
NUDC	-0.024	0.089	-10000	0	-0.23	76	76
regulation of attachment of spindle microtubules to kinetochore	-0.029	0.099	0.12	2	-0.26	71	73
spindle assembly	0.002	0.027	0.084	11	-0.1	8	19
spindle stabilization	0.007	0.029	0.11	3	-0.16	6	9
APC/C/HCDH1	0.023	0.007	-10000	0	-10000	0	0
MKLP2/PLK1	-0.033	0.1	0.12	2	-0.24	95	97
CCNB1	0.017	0.038	-10000	0	-0.14	2	2
PPP1CB	0.027	0.002	-10000	0	-10000	0	0
BTRC	0.025	0.005	-10000	0	-10000	0	0
ROCK2	-0.004	0.085	-10000	0	-0.39	22	22
TUBG1	0.008	0.021	-10000	0	-0.24	1	1
G2/M transition of mitotic cell cycle	-0.003	0.034	-10000	0	-0.23	5	5
MLF1IP	-0.018	0.076	-10000	0	-0.31	30	30
INCENP	0.024	0.021	-10000	0	-0.44	1	1

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.011	0.086	-10000	0	-0.29	41	41
CRKL	0.026	0.008	-10000	0	-0.13	1	1
Rac1/GDP	0.017	0.007	-10000	0	-10000	0	0
DOCK1	0.022	0.035	-10000	0	-0.43	3	3
ITGA4	-0.008	0.1	-10000	0	-0.26	61	61
alpha4/beta7 Integrin/MAdCAM1	0.01	0.12	-10000	0	-0.24	90	90
EPO	0.013	0.03	-10000	0	-0.18	7	7
alpha4/beta7 Integrin	-0.005	0.1	-10000	0	-0.28	56	56
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.026	0.002	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.012	0.077	-10000	0	-0.29	26	26
EPO/EPOR (dimer)	0.027	0.025	-10000	0	-0.3	1	1
lamellipodium assembly	0.014	0.035	-10000	0	-0.26	4	4
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
PI3K	0.038	0.007	-10000	0	-10000	0	0
ARF6	0.026	0.004	-10000	0	-10000	0	0
JAK2	0.006	0.051	-10000	0	-0.22	22	22
PXN	0.026	0.004	-10000	0	-10000	0	0
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
MADCAM1	-0.034	0.13	-10000	0	-0.24	111	111
cell adhesion	0.008	0.12	-10000	0	-0.24	90	90
CRKL/CBL	0.036	0.012	-10000	0	-10000	0	0
ITGB1	0.023	0.012	-10000	0	-10000	0	0
SRC	-0.024	0.099	0.18	29	-0.24	67	96
ITGB7	0.001	0.091	-10000	0	-0.26	44	44
RAC1	0.023	0.009	-10000	0	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.009	0.11	-10000	0	-0.26	74	74
p130Cas/Crk/Dock1	-0.007	0.099	0.35	1	-0.22	63	64
VCAM1	-0.033	0.13	-10000	0	-0.3	85	85
RHOA	0.026	0.004	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.046	0.066	-10000	0	-0.23	23	23
BCAR1	-0.034	0.092	0.19	28	-0.23	67	95
EPOR	0.025	0.006	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.025	0.007	-10000	0	-10000	0	0
GIT1	0.026	0.002	-10000	0	-10000	0	0
Rac1/GTP	0.015	0.036	-10000	0	-0.27	4	4

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.01	0.096	0.22	66	-10000	0	66
GNAI2	0.025	0.005	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.016	0.094	-10000	0	-0.26	61	61
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.022	0.045	-10000	0	-0.43	5	5
RhoA/GTP	-0.009	0.097	-10000	0	-0.22	66	66
negative regulation of cAMP metabolic process	-0.018	0.099	-10000	0	-0.24	67	67
GNAZ	0.026	0.004	-10000	0	-10000	0	0
GNAI3	0.021	0.01	-10000	0	-10000	0	0
GNA12	0.022	0.009	-10000	0	-10000	0	0
S1PR5	-0.053	0.16	-10000	0	-0.3	124	124
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.019	0.1	-10000	0	-0.24	67	67
RhoA/GDP	0.019	0.003	-10000	0	-10000	0	0
RHOA	0.026	0.004	-10000	0	-10000	0	0
GNAI1	0.019	0.036	-10000	0	-0.43	3	3

×

Ephrin B reverse 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
EFNB2	0.022	0.029	-10000	0	-0.16	10	10
EPHB2	0.017	0.04	-10000	0	-0.43	3	3
EFNB1	-0.023	0.082	-10000	0	-0.31	32	32
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0	0.095	-10000	0	-0.25	46	46
Ephrin B2/EPHB1-2	0.016	0.082	-10000	0	-0.25	41	41
neuron projection morphogenesis	-0.009	0.085	-10000	0	-0.24	46	46
Ephrin B1/EPHB1-2/Tiam1	-0.008	0.11	-10000	0	-0.26	61	61
DNM1	-0.027	0.12	-10000	0	-0.22	107	107
cell-cell signaling	0	0.003	-10000	0	-10000	0	0
MAP2K4	-0.009	0.085	0.21	2	-0.51	13	15
YES1	-0.005	0.13	-10000	0	-0.77	13	13
Ephrin B1/EPHB1-2/NCK2	-0.008	0.11	-10000	0	-0.26	62	62
PI3K	0.027	0.091	-10000	0	-0.52	13	13
mol:GDP	-0.009	0.1	-10000	0	-0.26	61	61
ITGA2B	-0.012	0.12	-10000	0	-0.43	40	40
endothelial cell proliferation	0.025	0.022	-10000	0	-0.26	1	1
FYN	-0.003	0.12	-10000	0	-0.75	13	13
MAP3K7	-0.01	0.089	0.22	1	-0.54	13	14
FGR	-0.008	0.13	-10000	0	-0.76	13	13
TIAM1	0.026	0.004	-10000	0	-10000	0	0
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
RGS3	0.025	0.013	-10000	0	-0.13	3	3
cell adhesion	-0.012	0.11	-10000	0	-0.4	21	21
LYN	-0.002	0.12	-10000	0	-0.75	13	13
Ephrin B1/EPHB1-2/Src Family Kinases	-0.009	0.11	-10000	0	-0.69	13	13
Ephrin B1/EPHB1-2	-0.01	0.095	-10000	0	-0.58	13	13
SRC	-0.004	0.12	-10000	0	-0.74	13	13
ITGB3	-0.001	0.082	-10000	0	-0.19	64	64
EPHB1	-0.009	0.12	-10000	0	-0.43	39	39
EPHB4	0.021	0.011	-10000	0	-10000	0	0
RAC1	0.023	0.009	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.025	0.022	-10000	0	-0.26	1	1
alphaIIb/beta3 Integrin	-0.01	0.11	-10000	0	-0.31	53	53
BLK	-0.01	0.13	-10000	0	-0.74	13	13
HCK	-0.004	0.13	-10000	0	-0.76	13	13
regulation of stress fiber formation	0.009	0.1	0.26	62	-10000	0	62
MAPK8	-0.014	0.09	-10000	0	-0.5	13	13
Ephrin B1/EPHB1-2/RGS3	-0.008	0.11	-10000	0	-0.26	62	62
endothelial cell migration	0.026	0.11	0.19	96	-0.41	13	109
NCK2	0.026	0.002	-10000	0	-10000	0	0
PTPN13	0.023	0.052	-10000	0	-0.47	5	5
regulation of focal adhesion formation	0.009	0.1	0.26	62	-10000	0	62
chemotaxis	0.009	0.11	0.26	62	-10000	0	62
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
Rac1/GTP	-0.004	0.09	-10000	0	-0.24	46	46
angiogenesis	-0.009	0.095	-10000	0	-0.58	13	13
LCK	-0.019	0.13	-10000	0	-0.76	13	13

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0.003	0.095	0.32	38	-10000	0	38
KIRREL	-0.009	0.12	-10000	0	-0.42	40	40
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.003	0.095	-10000	0	-0.32	38	38
PLCG1	0.025	0.005	-10000	0	-10000	0	0
ARRB2	0.026	0.002	-10000	0	-10000	0	0
WASL	0.02	0.011	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	0.029	0.08	-10000	0	-0.24	38	38
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.003	0.069	-10000	0	-0.24	32	32
FYN	-0.009	0.076	0.18	22	-0.22	39	61
mol:Ca2+	0.026	0.08	-10000	0	-0.24	39	39
mol:DAG	0.027	0.081	-10000	0	-0.24	39	39
NPHS2	0.001	0.033	-10000	0	-0.44	1	1
mol:IP3	0.027	0.081	-10000	0	-0.24	39	39
regulation of endocytosis	0.023	0.072	-10000	0	-0.21	39	39
Nephrin/NEPH1/podocin/Cholesterol	0.016	0.076	-10000	0	-0.24	39	39
establishment of cell polarity	-0.003	0.095	-10000	0	-0.32	38	38
Nephrin/NEPH1/podocin/NCK1-2	0.04	0.082	-10000	0	-0.22	38	38
Nephrin/NEPH1/beta Arrestin2	0.025	0.074	-10000	0	-0.22	39	39
NPHS1	-0.001	0.053	-10000	0	-0.15	40	40
Nephrin/NEPH1/podocin	0.018	0.073	-10000	0	-0.23	39	39
TJP1	0.026	0.003	-10000	0	-10000	0	0
NCK1	0.025	0.02	-10000	0	-0.43	1	1
NCK2	0.026	0.002	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.028	0.081	-10000	0	-0.24	39	39
CD2AP	0.026	0.002	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	0.027	0.08	-10000	0	-0.24	38	38
GRB2	0.025	0.006	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.014	0.087	0.19	26	-0.23	46	72
cytoskeleton organization	-0.017	0.083	0.2	12	-0.27	32	44
Nephrin/NEPH1	0.009	0.067	-10000	0	-0.22	38	38
Nephrin/NEPH1/ZO-1	0.021	0.081	-10000	0	-0.25	38	38

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	0.008	0.077	-10000	0	-0.22	50	50
RGS9BP	0.017	0.05	-10000	0	-0.39	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
GRK1	0.021	0.015	-10000	0	-0.13	1	1
mol:Na +	-0.019	0.088	-10000	0	-0.25	51	51
mol:ADP	0.005	0.016	-10000	0	-10000	0	0
GNAT2	0.015	0.018	-10000	0	-0.13	2	2
RGS9-1/Gbeta5/R9AP	0.019	0.088	-10000	0	-0.27	40	40
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.02	0.025	-10000	0	-0.13	1	1
GRK7	0.017	0.023	-10000	0	-0.13	6	6
CNGB3	0.004	0.032	-10000	0	-0.13	16	16
Cone Metarhodopsin II/X-Arrestin	0.013	0.006	-10000	0	-10000	0	0
mol:Ca2+	-0.055	0.11	0.18	18	-0.26	94	112
Cone PDE6	0.034	0.086	-10000	0	-0.23	40	40
Cone Metarhodopsin II	0.029	0.013	-10000	0	-10000	0	0
Na + (4 Units)	-0.025	0.12	-10000	0	-0.24	109	109
GNAT2/GDP	0.024	0.078	-10000	0	-0.22	40	40
GNB5	0.026	0.003	-10000	0	-10000	0	0
mol:GMP (4 units)	-0.004	0.03	0.18	8	-10000	0	8
Cone Transducin	0.009	0.083	-10000	0	-0.23	50	50
SLC24A2	-0.042	0.15	-10000	0	-0.43	59	59
GNB3/GNGT2	-0.001	0.1	-10000	0	-0.31	51	51
GNB3	-0.007	0.12	-10000	0	-0.4	38	38
GNAT2/GTP	0.014	0.01	-10000	0	-10000	0	0
CNGA3	-0.049	0.14	-10000	0	-0.43	54	54
ARR3	-0.007	0.018	-10000	0	-0.13	1	1
absorption of light	0	0	-10000	0	-10000	0	0
cGMP/Cone CNG Channel	-0.019	0.089	-10000	0	-0.26	51	51
mol:Pi	0.017	0.088	-10000	0	-0.27	40	40
Cone CNG Channel	0.009	0.082	-10000	0	-0.21	47	47
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	-0.042	0.15	-10000	0	-0.43	59	59
RGS9	-0.011	0.12	-10000	0	-0.39	44	44
PDE6C	0.004	0.025	-10000	0	-0.13	5	5
GNGT2	0.008	0.082	-10000	0	-0.3	28	28
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	0.005	0.036	-10000	0	-10000	0	0

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.009	0.2	0.48	7	-0.66	17	24
CRP	-0.016	0.2	0.59	5	-0.67	17	22
cell cycle arrest	-0.021	0.22	0.49	3	-0.66	29	32
TIMP1	-0.013	0.2	0.46	2	-0.68	20	22
IL6ST	-0.008	0.11	-10000	0	-0.43	32	32
Rac1/GDP	-0.05	0.16	-10000	0	-0.42	59	59
AP1	0.033	0.1	-10000	0	-0.58	2	2
GAB2	0.026	0.005	-10000	0	-10000	0	0
TNFSF11	-0.018	0.2	0.5	2	-0.69	15	17
HSP90B1	0.012	0.16	-10000	0	-0.91	14	14
GAB1	0.025	0.021	-10000	0	-0.43	1	1
MAPK14	-0.073	0.19	-10000	0	-0.54	56	56
AKT1	0.035	0.049	-10000	0	-0.7	1	1
FOXO1	0.035	0.051	-10000	0	-0.66	1	1
MAP2K6	-0.059	0.16	0.2	2	-0.45	59	61
mol:GTP	0	0.002	-10000	0	-10000	0	0
MAP2K4	-0.049	0.17	0.29	3	-0.44	53	56
MITF	-0.05	0.15	-10000	0	-0.41	56	56
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.025	0.006	-10000	0	-10000	0	0
A2M	0.017	0.082	-10000	0	-1.2	2	2
CEBPB	0.017	0.073	-10000	0	-0.36	17	17
GRB2/SOS1/GAB family/SHP2	0.007	0.081	-10000	0	-0.43	6	6
STAT3	-0.028	0.24	0.5	3	-0.7	30	33
STAT1	0.017	0.045	-10000	0	-0.9	1	1
CEBPD	-0.044	0.3	0.49	4	-1	35	39
PIK3CA	0.026	0.02	-10000	0	-0.43	1	1
PI3K	0.04	0.007	-10000	0	-10000	0	0
JUN	0.019	0.023	-10000	0	-0.13	9	9
PIAS3/MITF	-0.032	0.16	-10000	0	-0.41	50	50
MAPK11	-0.076	0.19	-10000	0	-0.56	54	54
STAT3 (dimer)/FOXO1	-0.007	0.17	-10000	0	-0.56	18	18
GRB2/SOS1/GAB family	-0.012	0.15	-10000	0	-0.42	34	34
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.046	0.15	-10000	0	-0.34	83	83
GRB2	0.025	0.006	-10000	0	-10000	0	0
JAK2	0.025	0.006	-10000	0	-10000	0	0
LBP	0.001	0.19	0.44	8	-0.6	22	30
PIK3R1	0.027	0.003	-10000	0	-10000	0	0
JAK1	0.019	0.016	-10000	0	-10000	0	0
MYC	-0.022	0.28	0.49	4	-0.87	36	40
FGG	-0.02	0.2	0.5	2	-0.67	17	19
macrophage differentiation	-0.021	0.22	0.49	3	-0.66	29	32
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0.003	0.12	-10000	0	-0.27	61	61
JUNB	-0.021	0.24	0.45	10	-0.81	22	32
FOS	-0.031	0.14	-10000	0	-0.43	48	48
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.051	0.16	0.23	1	-0.41	62	63
STAT1/PIAS1	-0.022	0.16	0.24	1	-0.4	48	49
GRB2/SOS1/GAB family/SHP2/PI3K	0.036	0.049	-10000	0	-0.34	6	6
STAT3 (dimer)	-0.025	0.24	0.5	3	-0.7	29	32
PRKCD	-0.026	0.23	0.41	28	-0.55	50	78
IL6R	0.005	0.082	-10000	0	-0.35	22	22
SOCS3	-0.094	0.3	0.39	2	-1.1	38	40
gp130 (dimer)/JAK1/JAK1/LMO4	0.02	0.078	-10000	0	-0.24	32	32
Rac1/GTP	-0.05	0.17	-10000	0	-0.43	59	59
HCK	0.014	0.063	-10000	0	-0.27	19	19
MAPKKK cascade	0.032	0.08	-10000	0	-0.96	1	1
bone resorption	-0.016	0.19	0.5	2	-0.63	17	19
IRF1	-0.015	0.2	0.51	3	-0.69	15	18
mol:GDP	-0.058	0.16	0.2	1	-0.43	62	63
SOS1	0.026	0.002	-10000	0	-10000	0	0
VAV1	-0.058	0.16	0.2	1	-0.44	62	63
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.1	0.25	-10000	0	-0.49	111	111
PTPN11	0.009	0.079	-10000	0	-0.69	6	6
IL6/IL6RA	-0.024	0.11	-10000	0	-0.32	51	51
gp130 (dimer)/TYK2/TYK2/LMO4	0.021	0.074	-10000	0	-0.25	30	30
gp130 (dimer)/JAK2/JAK2/LMO4	0.02	0.075	-10000	0	-0.25	31	31
IL6	-0.038	0.12	-10000	0	-0.41	40	40
PIAS3	0.024	0.008	-10000	0	-10000	0	0
PTPRE	0.023	0.024	-10000	0	-0.43	1	1
PIAS1	0.022	0.04	-10000	0	-0.43	4	4
RAC1	0.023	0.009	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.035	0.12	0.21	1	-0.31	65	66
LMO4	0.018	0.02	-10000	0	-10000	0	0
STAT3 (dimer)/PIAS3	-0.028	0.22	-10000	0	-0.67	28	28
MCL1	0.039	0.057	-10000	0	-0.62	1	1

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.017	0.048	-10000	0	-0.43	4	4
HSPA8	0.023	0.022	-10000	0	-0.43	1	1
SMAD3/SMAD4/ER alpha	0.017	0.092	0.21	2	-0.27	20	22
AKT1	0.015	0.034	-10000	0	-10000	0	0
GSC	-0.17	0.49	-10000	0	-1.4	71	71
NKX2-5	0	0.005	-10000	0	-10000	0	0
muscle cell differentiation	0.062	0.17	0.36	100	-10000	0	100
SMAD2-3/SMAD4/SP1	0.02	0.12	-10000	0	-0.27	34	34
SMAD4	-0.009	0.069	-10000	0	-0.23	13	13
CBFB	0.026	0.002	-10000	0	-10000	0	0
SAP18	0.025	0.006	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.028	0.08	-10000	0	-0.26	23	23
SMAD3/SMAD4/VDR	0.037	0.11	-10000	0	-0.24	35	35
MYC	0.009	0.087	-10000	0	-0.38	22	22
CDKN2B	-0.18	0.49	-10000	0	-1.5	60	60
AP1	0.001	0.092	-10000	0	-0.26	30	30
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.004	0.083	-10000	0	-0.31	17	17
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.037	0.14	-10000	0	-0.37	62	62
SP3	0.027	0.01	-10000	0	-10000	0	0
CREB1	0.026	0.002	-10000	0	-10000	0	0
FOXH1	-0.003	0.076	-10000	0	-0.42	10	10
SMAD3/SMAD4/GR	0.039	0.084	-10000	0	-0.24	6	6
GATA3	-0.053	0.14	-10000	0	-0.44	53	53
SKI/SIN3/HDAC complex/NCoR1	0.014	0.061	-10000	0	-0.3	15	15
MEF2C/TIF2	-0.02	0.13	0.29	4	-0.29	48	52
endothelial cell migration	0.16	0.46	1.3	73	-10000	0	73
MAX	0.032	0.019	-10000	0	-10000	0	0
RBBP7	0.026	0.003	-10000	0	-10000	0	0
RBBP4	0.021	0.022	-10000	0	-0.43	1	1
RUNX2	0.017	0.057	-10000	0	-0.25	18	18
RUNX3	-0.001	0.091	-10000	0	-0.3	36	36
RUNX1	-0.007	0.1	-10000	0	-0.24	62	62
CTBP1	0.026	0.005	-10000	0	-10000	0	0
NR3C1	0.033	0.019	-10000	0	-10000	0	0
VDR	-0.014	0.11	-10000	0	-0.26	71	71
CDKN1A	-0.041	0.25	-10000	0	-1.3	20	20
KAT2B	0.021	0.018	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	-0.011	0.13	-10000	0	-0.3	71	71
DCP1A	0.026	0.004	-10000	0	-10000	0	0
SKI	0.022	0.01	-10000	0	-10000	0	0
SERPINE1	-0.17	0.47	-10000	0	-1.3	73	73
SMAD3/SMAD4/ATF2	0.019	0.086	-10000	0	-0.24	20	20
SMAD3/SMAD4/ATF3	0.014	0.091	-10000	0	-0.28	15	15
SAP30	0.025	0.005	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.041	0.061	0.19	6	-0.26	4	10
JUN	-0.014	0.082	-10000	0	-0.27	25	25
SMAD3/SMAD4/IRF7	0.019	0.084	-10000	0	-0.26	12	12
TFE3	0.014	0.035	-10000	0	-10000	0	0
COL1A2	0.005	0.093	-10000	0	-0.88	5	5
mesenchymal cell differentiation	-0.02	0.087	0.28	15	-10000	0	15
DLX1	-0.066	0.16	-10000	0	-0.43	76	76
TCF3	0.023	0.029	-10000	0	-0.43	2	2
FOS	-0.03	0.14	-10000	0	-0.39	57	57
SMAD3/SMAD4/Max	0.039	0.084	0.2	6	-0.22	10	16
Cbp/p300/SNIP1	0.036	0.043	-10000	0	-0.26	4	4
ZBTB17	0.023	0.014	-10000	0	-10000	0	0
LAMC1	-0.01	0.061	0.21	1	-0.31	2	3
TGIF2/HDAC complex/SMAD3/SMAD4	0.024	0.082	-10000	0	-0.26	14	14
IRF7	0.016	0.052	-10000	0	-0.21	20	20
ESR1	0.009	0.071	-10000	0	-0.27	25	25
HNF4A	-0.007	0.042	-10000	0	-0.13	40	40
MEF2C	-0.01	0.12	0.21	36	-0.28	51	87
SMAD2-3/SMAD4	0.008	0.1	-10000	0	-0.24	32	32
Cbp/p300/Src-1	0.043	0.049	-10000	0	-0.26	4	4
IGHV3OR16-13	0.001	0.023	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.02	0.045	-10000	0	-0.38	6	6
CREBBP	0.021	0.023	-10000	0	-10000	0	0
SKIL	0.021	0.049	-10000	0	-0.43	6	6
HDAC1	0.022	0.01	-10000	0	-10000	0	0
HDAC2	0.025	0.005	-10000	0	-10000	0	0
SNIP1	0.022	0.011	-10000	0	-10000	0	0
GCN5L2	0	0.014	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.019	0.083	-10000	0	-0.23	8	8
MSG1/HSC70	0.015	0.072	-10000	0	-0.3	20	20
SMAD2	0	0.059	-10000	0	-0.14	55	55
SMAD3	0.006	0.056	-10000	0	-0.21	3	3
SMAD3/E2F4-5/DP1/p107/SMAD4	0.008	0.06	-10000	0	-0.25	14	14
SMAD2/SMAD2/SMAD4	-0.005	0.043	-10000	0	-0.25	1	1
NCOR1	0.024	0.028	-10000	0	-0.43	2	2
NCOA2	-0.005	0.11	-10000	0	-0.43	34	34
NCOA1	0.026	0.003	-10000	0	-10000	0	0
MYOD/E2A	-0.045	0.13	-10000	0	-0.3	91	91
SMAD2-3/SMAD4/SP1/MIZ-1	0.02	0.12	-10000	0	-0.27	36	36
IFNB1	-0.01	0.06	0.19	1	-0.3	5	6
SMAD3/SMAD4/MEF2C	0.005	0.13	-10000	0	-0.31	36	36
CITED1	-0.001	0.093	-10000	0	-0.24	52	52
SMAD2-3/SMAD4/ARC105	0.023	0.1	-10000	0	-0.23	25	25
RBL1	0.012	0.077	-10000	0	-0.41	16	16
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.049	0.19	-10000	0	-0.54	60	60
RUNX1-3/PEBPB2	0.02	0.087	-10000	0	-0.24	48	48
SMAD7	-0.016	0.11	-10000	0	-0.38	22	22
MYC/MIZ-1	0.02	0.067	0.18	7	-0.29	18	25
SMAD3/SMAD4	-0.023	0.18	0.27	43	-0.43	67	110
IL10	-0.062	0.19	0.21	18	-0.48	68	86
PIASy/HDAC complex	0.022	0.023	-10000	0	-10000	0	0
PIAS3	0.02	0.017	-10000	0	-10000	0	0
CDK2	0.015	0.049	-10000	0	-0.44	4	4
IL5	-0.039	0.13	0.24	1	-0.38	32	33
CDK4	0.02	0.024	-10000	0	-10000	0	0
PIAS4	0.022	0.023	-10000	0	-10000	0	0
ATF3	0.006	0.072	-10000	0	-0.43	9	9
SMAD3/SMAD4/SP1	0.024	0.099	-10000	0	-0.25	22	22
FOXG1	-0.001	0.11	-10000	0	-0.43	30	30
FOXO3	0.002	0.037	-10000	0	-10000	0	0
FOXO1	0.002	0.038	-10000	0	-0.3	1	1
FOXO4	0.001	0.041	-10000	0	-0.27	2	2
heart looping	-0.01	0.12	0.21	36	-0.28	51	87
CEBPB	0.007	0.076	-10000	0	-0.36	17	17
SMAD3/SMAD4/DLX1	-0.026	0.14	-10000	0	-0.28	84	84
MYOD1	-0.09	0.17	-10000	0	-0.43	95	95
SMAD3/SMAD4/HNF4	0.021	0.079	-10000	0	-0.22	12	12
SMAD3/SMAD4/GATA3	-0.026	0.15	-10000	0	-0.32	83	83
SnoN/SIN3/HDAC complex/NCoR1	0.021	0.049	-10000	0	-0.43	6	6
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.017	0.11	-10000	0	-0.25	38	38
SMAD3/SMAD4/SP1-3	0.043	0.096	-10000	0	-0.27	12	12
MED15	0.026	0.004	-10000	0	-10000	0	0
SP1	0.013	0.038	-10000	0	-0.16	3	3
SIN3B	0.025	0.006	-10000	0	-10000	0	0
SIN3A	0.026	0.003	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.006	0.12	-10000	0	-0.26	74	74
ITGB5	-0.007	0.08	-10000	0	-0.44	7	7
TGIF/SIN3/HDAC complex/CtBP	0.012	0.074	-10000	0	-0.46	10	10
SMAD3/SMAD4/AR	-0.019	0.13	-10000	0	-0.29	76	76
AR	-0.047	0.16	-10000	0	-0.33	104	104
negative regulation of cell growth	-0.002	0.094	-10000	0	-0.38	18	18
SMAD3/SMAD4/MYOD	-0.037	0.14	-10000	0	-0.29	102	102
E2F5	0.023	0.029	-10000	0	-0.43	2	2
E2F4	0.026	0.003	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.012	0.11	-10000	0	-0.22	72	72
SMAD2-3/SMAD4/FOXO1-3a-4	-0.028	0.14	-10000	0	-0.4	55	55
TFDP1	0.025	0.021	-10000	0	-0.43	1	1
SMAD3/SMAD4/AP1	0.022	0.1	-10000	0	-0.26	30	30
SMAD3/SMAD4/RUNX2	0.021	0.087	-10000	0	-0.28	15	15
TGIF2	0.021	0.045	-10000	0	-0.38	6	6
TGIF1	0.016	0.06	-10000	0	-0.27	17	17
ATF2	0.016	0.069	-10000	0	-0.43	12	12

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.047	0.09	-10000	0	-0.84	3	3
SMARCC2	0.024	0.017	-10000	0	-10000	0	0
SMARCC1	0.024	0.017	-10000	0	-10000	0	0
TBX21	-0.067	0.17	-10000	0	-0.67	32	32
SUMO2	0.023	0.016	-10000	0	-10000	0	0
STAT1 (dimer)	0.024	0.033	-10000	0	-0.16	10	10
FKBP4	0.025	0.007	-10000	0	-10000	0	0
FKBP5	-0.037	0.15	-10000	0	-0.34	89	89
GR alpha/HSP90/FKBP51/HSP90	0.049	0.12	0.26	20	-0.23	48	68
PRL	-0.034	0.068	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/TIF2	0.11	0.19	0.48	54	-0.33	2	56
RELA	-0.032	0.092	-10000	0	-0.26	23	23
FGG	0.09	0.14	0.4	43	-10000	0	43
GR beta/TIF2	0.056	0.12	0.28	26	-0.29	31	57
IFNG	-0.13	0.18	-10000	0	-0.58	27	27
apoptosis	0.014	0.17	0.57	19	-0.47	11	30
CREB1	0.026	0.009	-10000	0	-10000	0	0
histone acetylation	-0.048	0.1	-10000	0	-0.33	35	35
BGLAP	-0.039	0.097	-10000	0	-0.78	2	2
GR/PKAc	0.076	0.068	0.28	10	-10000	0	10
NF kappa B1 p50/RelA	-0.05	0.15	-10000	0	-0.31	108	108
SMARCD1	0.024	0.017	-10000	0	-10000	0	0
MDM2	0.047	0.063	0.2	44	-10000	0	44
GATA3	-0.032	0.14	-10000	0	-0.42	49	49
AKT1	0.022	0.013	0.18	2	-10000	0	2
CSF2	-0.056	0.084	-10000	0	-10000	0	0
GSK3B	0.023	0.026	-10000	0	-0.43	1	1
NR1I3	0.021	0.17	0.55	19	-0.53	6	25
CSN2	0.074	0.12	0.34	33	-10000	0	33
BRG1/BAF155/BAF170/BAF60A	0.06	0.047	-10000	0	-0.22	11	11
NFATC1	0.005	0.095	-10000	0	-0.43	23	23
POU2F1	0.025	0.021	-10000	0	-0.43	1	1
CDKN1A	-0.044	0.28	-10000	0	-1.4	20	20
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0	0.01	-10000	0	-10000	0	0
SFN	-0.023	0.11	-10000	0	-0.22	90	90
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.032	0.12	0.27	12	-0.23	58	70
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.04	0.27	0.54	16	-0.76	54	70
JUN	-0.078	0.13	0.27	2	-0.38	43	45
IL4	-0.062	0.12	-10000	0	-0.52	14	14
CDK5R1	0	0.1	-10000	0	-0.42	30	30
PRKACA	0.025	0.005	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.092	0.1	-10000	0	-0.32	53	53
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.051	0.11	0.28	11	-0.21	44	55
cortisol/GR alpha (monomer)	0.14	0.19	0.54	56	-10000	0	56
NCOA2	-0.005	0.11	-10000	0	-0.43	34	34
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.071	0.14	-10000	0	-0.42	57	57
AP-1/NFAT1-c-4	-0.17	0.23	-10000	0	-0.55	87	87
AFP	-0.077	0.12	-10000	0	-0.5	5	5
SUV420H1	0.025	0.005	-10000	0	-10000	0	0
IRF1	0.084	0.096	0.39	12	-10000	0	12
TP53	0.004	0.12	-10000	0	-0.47	32	32
PPP5C	0.022	0.01	-10000	0	-10000	0	0
KRT17	-0.27	0.42	-10000	0	-1.1	98	98
KRT14	-0.057	0.086	-10000	0	-10000	0	0
TBP	0.03	0.016	-10000	0	-0.29	1	1
CREBBP	0.025	0.046	-10000	0	-0.25	14	14
HDAC1	0.02	0.009	-10000	0	-10000	0	0
HDAC2	0.025	0.005	-10000	0	-10000	0	0
AP-1	-0.17	0.23	-10000	0	-0.55	89	89
MAPK14	0.024	0.015	-10000	0	-10000	0	0
MAPK10	0.021	0.038	-10000	0	-0.43	3	3
MAPK11	0.016	0.058	-10000	0	-0.43	8	8
KRT5	-0.24	0.39	-10000	0	-1.1	84	84
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
NCOA1	0.027	0.009	-10000	0	-10000	0	0
STAT1	0.024	0.033	-10000	0	-0.16	10	10
CGA	-0.048	0.085	-10000	0	-0.4	1	1
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.044	0.09	0.31	8	-0.38	4	12
MAPK3	0.024	0.016	-10000	0	-10000	0	0
MAPK1	0.024	0.015	-10000	0	-10000	0	0
ICAM1	-0.098	0.19	-10000	0	-0.64	31	31
NFKB1	-0.031	0.089	-10000	0	-0.22	34	34
MAPK8	-0.079	0.12	0.31	1	-0.35	51	52
MAPK9	0.023	0.015	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.012	0.18	0.57	19	-0.48	13	32
BAX	-0.024	0.11	-10000	0	-0.6	1	1
POMC	-0.086	0.22	-10000	0	-1.5	9	9
EP300	0.021	0.061	-10000	0	-0.29	18	18
cortisol/GR alpha (dimer)/p53	0.12	0.18	0.49	47	-0.46	1	48
proteasomal ubiquitin-dependent protein catabolic process	0.024	0.053	0.19	18	-10000	0	18
SGK1	0.002	0.24	-10000	0	-1.4	14	14
IL13	-0.13	0.19	-10000	0	-0.68	19	19
IL6	-0.14	0.29	-10000	0	-0.89	52	52
PRKACG	0.01	0.024	-10000	0	-10000	0	0
IL5	-0.1	0.15	-10000	0	-0.69	4	4
IL2	-0.13	0.18	-10000	0	-0.6	21	21
CDK5	0.02	0.012	-10000	0	-10000	0	0
PRKACB	0.021	0.01	-10000	0	-10000	0	0
HSP90AA1	0.025	0.005	-10000	0	-10000	0	0
IL8	-0.19	0.35	-10000	0	-0.9	86	86
CDK5R1/CDK5	0.015	0.071	-10000	0	-0.3	22	22
NF kappa B1 p50/RelA/PKAc	-0.007	0.12	-10000	0	-0.3	24	24
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.13	0.16	0.45	52	-10000	0	52
SMARCA4	0.024	0.016	-10000	0	-10000	0	0
chromatin remodeling	0.079	0.12	0.34	28	-0.37	6	34
NF kappa B1 p50/RelA/Cbp	-0.014	0.15	-10000	0	-0.38	34	34
JUN (dimer)	-0.077	0.13	0.27	2	-0.38	43	45
YWHAH	0.019	0.033	-10000	0	-10000	0	0
VIPR1	-0.071	0.18	-10000	0	-0.67	35	35
NR3C1	0.083	0.12	0.35	44	-10000	0	44
NR4A1	0.008	0.087	-10000	0	-0.45	15	15
TIF2/SUV420H1	0.015	0.083	-10000	0	-0.3	32	32
MAPKKK cascade	0.014	0.17	0.57	19	-0.47	11	30
cortisol/GR alpha (dimer)/Src-1	0.14	0.17	0.48	55	-10000	0	55
PBX1	0.025	0.021	-10000	0	-0.43	1	1
POU1F1	0	0.021	-10000	0	-10000	0	0
SELE	-0.15	0.28	-10000	0	-0.81	63	63
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.078	0.12	0.35	27	-0.37	6	33
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.13	0.16	0.45	52	-10000	0	52
mol:cortisol	0.066	0.11	0.31	53	-10000	0	53
MMP1	-0.041	0.09	-10000	0	-0.94	2	2

×

Canonical Wnt signaling pathway

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
HDAC1	0.024	0.024	0.19	4	-10000	0	4
AES	0.026	0.019	0.17	3	-10000	0	3
FBXW11	0.026	0.004	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.03	0.017	-10000	0	-10000	0	0
SMAD4	0.026	0.004	-10000	0	-10000	0	0
DKK2	-0.039	0.14	-10000	0	-0.26	112	112
TLE1	0.025	0.035	0.18	4	-0.43	2	6
MACF1	0.022	0.01	-10000	0	-10000	0	0
CTNNB1	0.044	0.099	0.28	30	-0.3	5	35
WIF1	-0.13	0.18	-10000	0	-0.27	266	266
beta catenin/RanBP3	0.016	0.1	0.4	27	-0.3	1	28
KREMEN2	-0.007	0.1	-10000	0	-0.24	63	63
DKK1	-0.035	0.13	-10000	0	-0.25	112	112
beta catenin/beta TrCP1	0.053	0.097	0.28	27	-0.28	4	31
FZD1	0.021	0.01	-10000	0	-10000	0	0
AXIN2	0.003	0.16	0.58	18	-0.89	5	23
AXIN1	0.027	0.002	-10000	0	-10000	0	0
RAN	0.026	0.003	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.021	0.075	-10000	0	-0.53	8	8
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.066	0.09	0.3	15	-0.58	3	18
Axin1/APC/GSK3	0.03	0.073	0.24	13	-0.25	2	15
Axin1/APC/GSK3/beta catenin/Macf1	0.043	0.075	0.24	15	-0.42	2	17
HNF1A	0.027	0.029	0.19	4	-0.43	1	5
CTBP1	0.027	0.021	0.19	4	-10000	0	4
MYC	0.008	0.36	0.55	64	-1.5	21	85
RANBP3	0.025	0.006	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0	0.11	-10000	0	-0.27	68	68
NKD1	0.016	0.059	-10000	0	-0.28	16	16
TCF4	0.026	0.027	0.18	4	-0.38	1	5
TCF3	0.025	0.032	0.18	3	-0.37	2	5
WNT1/LRP6/FZD1/Axin1	0.052	0.03	-10000	0	-10000	0	0
Ran/GTP	0.019	0.003	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.019	0.13	0.5	29	-0.36	1	30
LEF1	0.026	0.026	0.18	4	-0.14	5	9
DVL1	0.027	0.037	-10000	0	-0.26	1	1
CSNK2A1	0.025	0.005	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.062	0.11	0.3	16	-0.73	3	19
DKK1/LRP6/Kremen 2	0.002	0.11	-10000	0	-0.25	71	71
LRP6	0.026	0.005	-10000	0	-10000	0	0
CSNK1A1	0.028	0.022	0.19	4	-10000	0	4
NLK	0.024	0.013	-10000	0	-0.16	1	1
CCND1	-0.018	0.25	0.56	19	-1.5	11	30
WNT1	0.01	0.04	-10000	0	-0.13	33	33
GSK3A	0.022	0.01	-10000	0	-10000	0	0
GSK3B	0.025	0.02	-10000	0	-0.43	1	1
FRAT1	0.023	0.03	-10000	0	-0.43	2	2
PPP2R5D	0.026	0.057	0.28	8	-0.28	2	10
APC	0.038	0.079	0.19	101	-10000	0	101
WNT1/LRP6/FZD1	0.042	0.079	0.2	75	-0.2	2	77
CREBBP	0.028	0.021	0.19	4	-10000	0	4

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.018	0.1	-10000	0	-0.25	53	53
MAP4K1	0.013	0.061	-10000	0	-0.34	13	13
MAP3K8	0.016	0.047	-10000	0	-0.2	17	17
PRKCB	-0.007	0.098	-10000	0	-0.22	68	68
DBNL	0.023	0.009	-10000	0	-10000	0	0
CRKL	0.026	0.008	-10000	0	-0.13	1	1
MAP3K1	-0.007	0.082	0.17	1	-0.36	10	11
JUN	-0.025	0.17	-10000	0	-0.57	42	42
MAP3K7	-0.007	0.081	-10000	0	-0.36	10	10
GRAP2	-0.007	0.1	-10000	0	-0.43	25	25
CRK	0.026	0.002	-10000	0	-10000	0	0
MAP2K4	-0.002	0.092	0.26	4	-0.35	12	16
LAT	0.003	0.1	-10000	0	-0.43	26	26
LCP2	0.02	0.033	-10000	0	-0.15	15	15
MAPK8	-0.023	0.18	-10000	0	-0.6	43	43
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.002	0.089	-10000	0	-0.28	26	26
LAT/GRAP2/SLP76/HPK1/HIP-55	0.022	0.098	-10000	0	-0.24	48	48

×

Noncanonical Wnt signaling pathway

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
NFATC2	-0.023	0.13	-10000	0	-0.32	71	71
GNB1/GNG2	0.021	0.097	-10000	0	-0.28	28	28
mol:DAG	0.003	0.089	0.21	13	-0.26	25	38
PLCG1	0.003	0.091	0.21	13	-0.27	25	38
YES1	-0.013	0.082	-10000	0	-0.27	40	40
FZD3	0.023	0.035	-10000	0	-0.43	3	3
FZD6	0.015	0.04	-10000	0	-0.43	1	1
G protein	0.025	0.1	0.26	3	-0.27	26	29
MAP3K7	-0.048	0.1	0.28	6	-0.3	24	30
mol:Ca2+	0.003	0.087	0.21	13	-0.26	25	38
mol:IP3	0.003	0.089	0.21	13	-0.26	25	38
NLK	0.01	0.044	-10000	0	-0.95	1	1
GNB1	0.022	0.01	-10000	0	-10000	0	0
CAMK2A	-0.048	0.11	0.21	13	-0.29	35	48
MAP3K7IP1	0	0	-10000	0	-10000	0	0
Noncanonical Wnts/FZD	-0.007	0.087	-10000	0	-0.27	44	44
CSNK1A1	0.026	0.003	-10000	0	-10000	0	0
GNAS	-0.013	0.079	0.16	1	-0.26	41	42
GO:0007205	-0.005	0.088	0.21	13	-0.27	25	38
WNT6	0.003	0.087	-10000	0	-0.43	17	17
WNT4	0.008	0.057	-10000	0	-0.43	5	5
NFAT1/CK1 alpha	-0.002	0.12	0.33	3	-0.32	27	30
GNG2	0.022	0.04	-10000	0	-0.43	4	4
WNT5A	0.01	0.078	-10000	0	-0.33	22	22
WNT11	0.009	0.075	-10000	0	-0.43	13	13
CDC42	0.001	0.064	-10000	0	-0.32	8	8

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.028	0.14	-10000	0	-0.42	55	55
KLHL20	0.011	0.07	0.16	6	-0.22	6	12
CYFIP2	0.022	0.037	-10000	0	-0.28	6	6
Rac1/GDP	-0.004	0.095	0.26	4	-0.26	47	51
ENAH	-0.032	0.14	-10000	0	-0.42	62	62
AP1M1	0.025	0.006	-10000	0	-10000	0	0
RAP1B	0.026	0.004	-10000	0	-10000	0	0
RAP1A	0.021	0.01	-10000	0	-10000	0	0
CTNNB1	0.026	0.004	-10000	0	-10000	0	0
CDC42/GTP	-0.004	0.065	-10000	0	-0.24	1	1
ABI1/Sra1/Nap1	-0.014	0.035	-10000	0	-0.15	6	6
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.021	0.12	-10000	0	-0.26	70	70
RAPGEF1	-0.019	0.14	0.24	5	-0.37	55	60
CTNND1	0.026	0.004	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.028	0.15	-10000	0	-0.43	62	62
CRK	-0.03	0.14	0.22	1	-0.4	57	58
E-cadherin/gamma catenin/alpha catenin	0.014	0.1	-10000	0	-0.26	63	63
alphaE/beta7 Integrin	0.019	0.069	-10000	0	-0.3	19	19
IQGAP1	0.02	0.043	-10000	0	-0.25	10	10
NCKAP1	0.026	0.002	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.037	0.025	-10000	0	-0.23	1	1
DLG1	-0.031	0.14	-10000	0	-0.42	61	61
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.014	0.044	-10000	0	-0.18	1	1
MLLT4	0.024	0.021	-10000	0	-0.43	1	1
ARF6/GTP/NME1/Tiam1	0.048	0.012	-10000	0	-10000	0	0
PI3K	-0.015	0.057	-10000	0	-0.23	1	1
ARF6	0.026	0.004	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
E-cadherin/gamma catenin	-0.02	0.12	-10000	0	-0.31	63	63
TIAM1	0.026	0.004	-10000	0	-10000	0	0
E-cadherin(dimer)/Ca2+	0.029	0.088	-10000	0	-0.22	55	55
AKT1	-0.003	0.043	0.12	2	-10000	0	2
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
CDH1	-0.046	0.15	-10000	0	-0.43	59	59
RhoA/GDP	0.004	0.1	0.26	8	-0.26	52	60
actin cytoskeleton organization	0.014	0.06	0.16	19	-0.16	6	25
CDC42/GDP	0	0.1	0.25	5	-0.25	51	56
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.014	0.079	-10000	0	-0.22	61	61
ITGB7	0.001	0.091	-10000	0	-0.26	44	44
RAC1	0.023	0.009	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.031	0.095	-10000	0	-0.23	55	55
E-cadherin/Ca2+/beta catenin/alpha catenin	0.015	0.085	-10000	0	-0.22	59	59
mol:GDP	-0.011	0.11	0.26	9	-0.3	52	61
CDC42/GTP/IQGAP1	0.027	0.028	-10000	0	-0.23	4	4
JUP	0.02	0.049	-10000	0	-0.39	7	7
p120 catenin/RhoA/GDP	0.009	0.1	0.26	6	-0.26	51	57
RAC1/GTP/IQGAP1	0.027	0.029	-10000	0	-0.26	4	4
PIP5K1C/AP1M1	0.037	0.009	-10000	0	-10000	0	0
RHOA	0.026	0.004	-10000	0	-10000	0	0
CDC42	0.022	0.01	-10000	0	-10000	0	0
CTNNA1	0.026	0.004	-10000	0	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.012	0.051	0.14	19	-0.17	14	33
NME1	0.026	0.004	-10000	0	-10000	0	0
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	-0.031	0.15	-10000	0	-0.42	62	62
regulation of cell-cell adhesion	-0.009	0.055	-10000	0	-0.21	1	1
WASF2	0.009	0.029	-10000	0	-10000	0	0
Rap1/GTP	0.001	0.082	0.24	2	-0.26	1	3
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.027	0.12	-10000	0	-0.25	74	74
CCND1	0.012	0.06	0.16	15	-0.2	14	29
VAV2	-0.013	0.15	-10000	0	-0.44	26	26
RAP1/GDP	0.004	0.091	0.27	4	-0.25	7	11
adherens junction assembly	-0.03	0.14	-10000	0	-0.4	62	62
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.023	0.008	-10000	0	-10000	0	0
PIP5K1C	0.025	0.006	-10000	0	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.016	0.11	-10000	0	-0.24	74	74
E-cadherin/beta catenin	-0.028	0.1	-10000	0	-0.32	57	57
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	-0.032	0.14	-10000	0	-0.42	60	60
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
Rac1/GTP	-0.016	0.084	-10000	0	-0.34	7	7
E-cadherin/beta catenin/alpha catenin	0.016	0.1	-10000	0	-0.26	59	59
ITGAE	0.026	0.002	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.028	0.15	-10000	0	-0.44	62	62

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.026	0.004	-9999	-10000	0	0
SVIL	0.015	0.042	-9999	-0.16	23	23
ZNF318	0.026	0.003	-9999	-10000	0	0
JMJD2C	0	0.005	-9999	-10000	0	0
T-DHT/AR/Ubc9	-0.02	0.11	-9999	-0.26	77	77
CARM1	0.025	0.006	-9999	-10000	0	0
PRDX1	0.012	0.066	-9999	-0.43	11	11
PELP1	0.026	0.002	-9999	-10000	0	0
CTNNB1	0.026	0.004	-9999	-10000	0	0
AKT1	0.025	0.005	-9999	-10000	0	0
PTK2B	0.018	0.032	-9999	-0.13	22	22
MED1	0.026	0.003	-9999	-10000	0	0
MAK	0.007	0.063	-9999	-0.16	51	51
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	0.011	0.069	-9999	-0.43	12	12
GSN	0.017	0.06	-9999	-0.37	11	11
NCOA2	-0.005	0.11	-9999	-0.43	34	34
NCOA6	0.025	0.005	-9999	-10000	0	0
DNA-PK	0.05	0.014	-9999	-10000	0	0
NCOA4	0.025	0.005	-9999	-10000	0	0
PIAS3	0.023	0.008	-9999	-10000	0	0
cell proliferation	-0.005	0.079	-9999	-0.52	10	10
XRCC5	0.026	0.003	-9999	-10000	0	0
UBE3A	0.026	0.003	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.03	0.12	-9999	-0.27	92	92
FHL2	-0.02	0.16	-9999	-0.98	12	12
RANBP9	0.026	0.003	-9999	-10000	0	0
JMJD1A	-0.009	0.038	-9999	-0.13	42	42
CDK6	0.004	0.083	-9999	-0.43	17	17
TGFB1I1	0.022	0.039	-9999	-0.23	9	9
T-DHT/AR/CyclinD1	-0.029	0.12	-9999	-0.27	87	87
XRCC6	0.026	0.004	-9999	-10000	0	0
T-DHT/AR	-0.026	0.12	-9999	-0.25	107	107
CTDSP1	0.026	0.003	-9999	-10000	0	0
CTDSP2	0.025	0.006	-9999	-10000	0	0
BRCA1	0.025	0.012	-9999	-0.13	3	3
TCF4	0.025	0.02	-9999	-0.43	1	1
CDKN2A	-0.012	0.11	-9999	-0.3	55	55
SRF	0.024	0.027	-9999	-10000	0	0
NKX3-1	-0.035	0.077	-9999	-0.17	105	105
KLK3	0.003	0.046	-9999	-10000	0	0
TMF1	0.025	0.02	-9999	-0.43	1	1
HNRNPA1	0.026	0.004	-9999	-10000	0	0
AOF2	0	0.001	-9999	-10000	0	0
APPL1	0.013	0.003	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.024	0.11	-9999	-0.26	80	80
AR	-0.056	0.16	-9999	-0.34	104	104
UBA3	0.026	0.004	-9999	-10000	0	0
PATZ1	0.026	0.004	-9999	-10000	0	0
PAWR	0.003	0.087	-9999	-0.25	44	44
PRKDC	0.025	0.005	-9999	-10000	0	0
PA2G4	0.026	0.003	-9999	-10000	0	0
UBE2I	0.026	0.002	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.017	0.099	-9999	-0.23	77	77
RPS6KA3	0.025	0.02	-9999	-0.43	1	1
T-DHT/AR/ARA70	-0.021	0.11	-9999	-0.26	78	78
LATS2	0.018	0.046	-9999	-0.21	15	15
T-DHT/AR/PRX1	-0.026	0.1	-9999	-0.24	86	86
Cyclin D3/CDK11 p58	0.019	0.005	-9999	-10000	0	0
VAV3	-0.031	0.11	-9999	-0.2	115	115
KLK2	-0.044	0.12	-9999	-0.41	40	40
CASP8	0.021	0.033	-9999	-0.23	3	3
T-DHT/AR/TIF2/CARM1	-0.017	0.12	-9999	-0.27	87	87
TMPRSS2	-0.082	0.25	-9999	-0.89	43	43
CCND1	0.011	0.07	-9999	-0.26	25	25
PIAS1	0.022	0.04	-9999	-0.43	4	4
mol:T-DHT	-0.006	0.019	-9999	-0.064	42	42
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.025	0.006	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.029	0.12	-9999	-0.28	79	79
CMTM2	0.013	0.073	-9999	-0.43	13	13
SNURF	0.011	0.079	-9999	-0.4	18	18
ZMIZ1	0.016	0.029	-9999	-10000	0	0
CCND3	0.026	0.007	-9999	-10000	0	0
TGIF1	0.016	0.06	-9999	-0.27	17	17
FKBP4	0.024	0.007	-9999	-10000	0	0

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.017	0.075	-10000	0	-0.21	55	55
TP53	-0.015	0.07	-10000	0	-0.29	25	25
Senescence	-0.015	0.07	-10000	0	-0.29	25	25
Apoptosis	-0.015	0.07	-10000	0	-0.29	25	25
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.01	0.056	0.21	34	-10000	0	34
MDM4	0.025	0.006	-10000	0	-10000	0	0

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0.001	0.14	-10000	0	-0.55	26	26
HDAC1	0.022	0.014	-10000	0	-10000	0	0
AES	0.025	0.007	-10000	0	-10000	0	0
FBXW11	0.026	0.004	-10000	0	-10000	0	0
DTX1	0.019	0.053	-10000	0	-0.39	8	8
LRP6/FZD1	0.03	0.017	-10000	0	-10000	0	0
TLE1	0.024	0.029	-10000	0	-0.43	2	2
AP1	-0.027	0.091	-10000	0	-0.25	60	60
NCSTN	0.026	0.004	-10000	0	-10000	0	0
ADAM10	0.015	0.069	-10000	0	-0.43	12	12
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.02	0.065	-10000	0	-10000	0	0
NICD/RBPSUH	0.016	0.12	-10000	0	-0.49	26	26
WIF1	-0.13	0.18	-10000	0	-0.27	266	266
NOTCH1	0	0.12	-10000	0	-0.52	26	26
PSENEN	0.022	0.01	-10000	0	-10000	0	0
KREMEN2	-0.007	0.1	-10000	0	-0.24	63	63
DKK1	-0.035	0.13	-10000	0	-0.25	112	112
beta catenin/beta TrCP1	0.011	0.072	0.28	6	-0.31	2	8
APH1B	0.026	0.003	-10000	0	-10000	0	0
APH1A	0.026	0.004	-10000	0	-10000	0	0
AXIN1	0.007	0.049	0.34	1	-10000	0	1
CtBP/CBP/TCF1/TLE1/AES	0.02	0.049	0.29	4	-0.26	3	7
PSEN1	0.025	0.005	-10000	0	-10000	0	0
FOS	-0.031	0.14	-10000	0	-0.43	48	48
JUN	0.019	0.023	-10000	0	-0.13	9	9
MAP3K7	0.025	0.006	-10000	0	-10000	0	0
CTNNB1	0.002	0.072	0.29	7	-0.33	2	9
MAPK3	0.026	0.002	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.007	0.11	-10000	0	-0.27	68	68
HNF1A	0.025	0.021	-10000	0	-0.43	1	1
CTBP1	0.026	0.006	-10000	0	-10000	0	0
MYC	-0.033	0.28	-10000	0	-1.4	21	21
NKD1	0.016	0.059	-10000	0	-0.28	16	16
FZD1	0.021	0.01	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	0.013	0.12	-10000	0	-0.5	26	26
apoptosis	-0.027	0.09	-10000	0	-0.25	60	60
Delta 1/NOTCHprecursor	-0.001	0.14	-10000	0	-0.55	26	26
DLL1	-0.008	0.12	-10000	0	-0.43	38	38
PPARD	0.022	0.058	-10000	0	-1.1	1	1
Gamma Secretase	0.063	0.032	-10000	0	-10000	0	0
APC	0.003	0.069	0.34	1	-0.47	4	5
DVL1	-0.012	0.07	-10000	0	-0.26	32	32
CSNK2A1	0.025	0.005	-10000	0	-10000	0	0
MAP3K7IP1	0	0.005	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	0.007	0.11	-10000	0	-0.25	71	71
LRP6	0.025	0.005	-10000	0	-10000	0	0
CSNK1A1	0.026	0.004	-10000	0	-10000	0	0
NLK	0.014	0.011	-10000	0	-10000	0	0
CCND1	-0.01	0.21	-10000	0	-1.3	13	13
WNT1	0.007	0.04	-10000	0	-0.13	33	33
Axin1/APC/beta catenin	0.004	0.094	0.3	6	-0.42	3	9
DKK2	-0.039	0.14	-10000	0	-0.26	112	112
NOTCH1 precursor/DVL1	-0.019	0.14	-10000	0	-0.53	24	24
GSK3B	0.025	0.02	-10000	0	-0.43	1	1
FRAT1	0.023	0.03	-10000	0	-0.43	2	2
NOTCH/Deltex homolog 1	0.015	0.13	-10000	0	-0.51	26	26
PPP2R5D	0.01	0.052	0.25	8	-0.3	4	12
MAPK1	0.026	0.003	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.011	0.12	-10000	0	-0.24	98	98
RBPJ	0.026	0.004	-10000	0	-10000	0	0
CREBBP	0.027	0.007	-10000	0	-10000	0	0

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.006	0.052	0.2	30	-0.2	2	32
RFC1	0	0.037	0.18	18	-0.2	2	20
PRKDC	0.007	0.054	0.2	35	-0.2	2	37
RIPK1	0.027	0.004	-10000	0	-10000	0	0
CASP7	-0.016	0.14	-10000	0	-0.57	29	29
FASLG/FAS/FADD/FAF1	0.003	0.054	0.19	14	-0.25	9	23
MAP2K4	-0.028	0.11	0.22	1	-0.33	38	39
mol:ceramide	0.003	0.068	-10000	0	-0.26	18	18
GSN	-0.001	0.062	0.19	26	-0.3	9	35
FASLG/FAS/FADD/FAF1/Caspase 8	0.004	0.055	-10000	0	-0.26	6	6
FAS	0.011	0.064	-10000	0	-0.28	18	18
BID	-0.01	0.052	0.26	17	-10000	0	17
MAP3K1	-0.024	0.11	0.22	1	-0.35	33	34
MAP3K7	0.025	0.006	-10000	0	-10000	0	0
RB1	0.001	0.039	0.18	19	-0.2	2	21
CFLAR	0.026	0.008	-10000	0	-10000	0	0
HGF/MET	-0.006	0.12	-10000	0	-0.24	86	86
ARHGDIB	0.006	0.052	0.2	32	-0.22	1	33
FADD	0.022	0.014	-10000	0	-10000	0	0
actin filament polymerization	0.004	0.067	0.24	19	-0.19	26	45
NFKB1	-0.011	0.12	-10000	0	-0.75	11	11
MAPK8	-0.045	0.15	-10000	0	-0.47	43	43
DFFA	0	0.034	0.17	16	-0.2	2	18
DNA fragmentation during apoptosis	-0.003	0.045	0.18	17	-0.18	12	29
FAS/FADD/MET	-0.004	0.1	-10000	0	-0.26	57	57
CFLAR/RIP1	0.039	0.009	-10000	0	-10000	0	0
FAIM3	0.004	0.088	-10000	0	-0.43	18	18
FAF1	0.019	0.016	-10000	0	-10000	0	0
PARP1	0.001	0.039	0.18	19	-0.2	2	21
DFFB	0	0.034	0.17	16	-0.2	2	18
CHUK	-0.011	0.11	-10000	0	-0.71	10	10
FASLG	0.007	0.04	-10000	0	-0.13	32	32
FAS/FADD	0.024	0.049	-10000	0	-0.31	8	8
HGF	-0.009	0.091	-10000	0	-0.2	69	69
LMNA	-0.001	0.047	0.2	12	-0.21	1	13
CASP6	0.001	0.041	0.19	18	-0.22	3	21
CASP10	0.022	0.015	-10000	0	-0.13	1	1
CASP3	0.003	0.046	0.22	18	-0.22	2	20
PTPN13	0.022	0.041	-10000	0	-0.37	5	5
CASP8	-0.01	0.066	0.34	17	-10000	0	17
IL6	-0.099	0.36	-10000	0	-1.2	47	47
MET	-0.047	0.14	-10000	0	-0.43	52	52
ICAD/CAD	0.001	0.044	0.3	6	-0.21	1	7
FASLG/FAS/FADD/FAF1/Caspase 10	0.003	0.069	-10000	0	-0.27	17	17
activation of caspase activity by cytochrome c	-0.01	0.051	0.26	17	-10000	0	17
PAK2	0.002	0.041	0.19	21	-0.22	1	22
BCL2	0.021	0.045	-10000	0	-0.43	5	5

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.007	0.089	-10000	0	-0.26	49	49
cell-cell adhesion	0.02	0.05	0.22	25	-10000	0	25
Ephrin B/EPHB2/RasGAP	0.054	0.058	-10000	0	-0.24	12	12
ITSN1	0.026	0.003	-10000	0	-10000	0	0
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
SHC1	0.024	0.014	-10000	0	-10000	0	0
Ephrin B1/EPHB3	0.033	0.012	-10000	0	-10000	0	0
Ephrin B1/EPHB1	0.012	0.077	-10000	0	-0.26	38	38
HRAS/GDP	0.018	0.064	-10000	0	-0.27	10	10
Ephrin B/EPHB1/GRB7	0.042	0.098	-10000	0	-0.26	45	45
Endophilin/SYNJ1	0.012	0.056	0.18	26	-0.22	13	39
KRAS	0.025	0.005	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	0.045	0.088	-10000	0	-0.24	38	38
endothelial cell migration	0.042	0.028	-10000	0	-0.22	1	1
GRB2	0.025	0.006	-10000	0	-10000	0	0
GRB7	0.001	0.044	-10000	0	-0.13	41	41
PAK1	-0.012	0.065	0.29	3	-0.23	14	17
HRAS	0.025	0.006	-10000	0	-10000	0	0
RRAS	0.01	0.054	0.18	22	-0.23	11	33
DNM1	-0.027	0.12	-10000	0	-0.22	108	108
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.005	0.08	0.19	17	-0.23	45	62
lamellipodium assembly	-0.02	0.05	-10000	0	-0.22	25	25
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.011	0.074	-10000	0	-0.3	10	10
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
EPHB2	0.017	0.04	-10000	0	-0.43	3	3
EPHB3	0.025	0.011	-10000	0	-0.13	2	2
EPHB1	-0.009	0.12	-10000	0	-0.43	39	39
EPHB4	0.021	0.011	-10000	0	-10000	0	0
mol:GDP	-0.002	0.057	0.23	3	-0.3	7	10
Ephrin B/EPHB2	0.042	0.053	-10000	0	-0.24	13	13
Ephrin B/EPHB3	0.052	0.045	-10000	0	-0.23	11	11
JNK cascade	-0.003	0.078	0.45	2	-0.23	39	41
Ephrin B/EPHB1	0.031	0.089	-10000	0	-0.24	45	45
RAP1/GDP	0.044	0.095	0.23	64	-0.28	8	72
EFNB2	0.022	0.029	-10000	0	-0.16	10	10
EFNB3	0.016	0.064	-10000	0	-0.36	13	13
EFNB1	0.025	0.012	-10000	0	-0.13	3	3
Ephrin B2/EPHB1-2	0.017	0.082	-10000	0	-0.25	41	41
RAP1B	0.026	0.004	-10000	0	-10000	0	0
RAP1A	0.021	0.01	-10000	0	-10000	0	0
CDC42/GTP	0.015	0.077	-10000	0	-0.32	11	11
Rap1/GTP	-0.001	0.073	-10000	0	-0.29	12	12
axon guidance	-0.007	0.088	-10000	0	-0.26	49	49
MAPK3	0.002	0.066	0.19	1	-0.29	8	9
MAPK1	0.002	0.066	0.19	1	-0.29	8	9
Rac1/GDP	0.024	0.084	0.23	40	-0.28	8	48
actin cytoskeleton reorganization	-0.004	0.047	-10000	0	-0.27	7	7
CDC42/GDP	0.04	0.098	0.23	69	-0.28	8	77
PI3K	0.046	0.03	-10000	0	-0.22	1	1
EFNA5	-0.029	0.14	-10000	0	-0.43	48	48
Ephrin B2/EPHB4	0.025	0.022	-10000	0	-0.26	1	1
Ephrin B/EPHB2/Intersectin/N-WASP	0.014	0.045	-10000	0	-0.29	8	8
CDC42	0.022	0.01	-10000	0	-10000	0	0
RAS family/GTP	-0.005	0.07	-10000	0	-0.29	11	11
PTK2	0.054	0.16	0.54	52	-10000	0	52
MAP4K4	-0.003	0.079	0.46	2	-0.23	39	41
SRC	0.025	0.005	-10000	0	-10000	0	0
KALRN	0.02	0.038	-10000	0	-0.17	16	16
Intersectin/N-WASP	0.03	0.017	-10000	0	-10000	0	0
neuron projection morphogenesis	0.032	0.12	0.3	69	-0.34	4	73
MAP2K1	0.005	0.069	-10000	0	-0.3	9	9
WASL	0.02	0.011	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	0.03	0.086	-10000	0	-0.25	40	40
cell migration	0.004	0.087	0.39	1	-0.36	8	9
NRAS	0.021	0.01	-10000	0	-10000	0	0
SYNJ1	0.012	0.056	0.18	24	-0.22	13	37
PXN	0.026	0.004	-10000	0	-10000	0	0
TF	-0.022	0.075	0.17	20	-0.24	33	53
HRAS/GTP	0.016	0.082	-10000	0	-0.23	43	43
Ephrin B1/EPHB1-2	0.018	0.08	-10000	0	-0.24	39	39
cell adhesion mediated by integrin	0.002	0.048	0.21	11	-0.19	16	27
RAC1	0.023	0.009	-10000	0	-10000	0	0
mol:GTP	0.02	0.087	-10000	0	-0.24	45	45
RAC1-CDC42/GTP	-0.004	0.059	-10000	0	-0.3	8	8
RASA1	0.026	0.003	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0.03	0.08	0.23	35	-0.29	6	41
ruffle organization	0.039	0.13	0.35	52	-0.42	3	55
NCK1	0.025	0.02	-10000	0	-0.43	1	1
receptor internalization	-0.024	0.075	0.17	20	-0.24	31	51
Ephrin B/EPHB2/KALRN	0.053	0.061	-10000	0	-0.24	14	14
ROCK1	0.02	0.031	0.18	17	-10000	0	17
RAS family/GDP	-0.007	0.044	-10000	0	-0.28	7	7
Rac1/GTP	-0.001	0.058	-10000	0	-0.23	25	25
Ephrin B/EPHB1/Src/Paxillin	0.006	0.074	-10000	0	-0.24	39	39

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.015	0.048	0.16	1	-0.25	13	14
EPHB2	0.017	0.04	-10000	0	-0.43	3	3
Syndecan-2/TACI	0.012	0.046	-10000	0	-0.24	14	14
LAMA1	-0.024	0.14	-10000	0	-0.43	51	51
Syndecan-2/alpha2 ITGB1	0.021	0.093	-10000	0	-0.26	43	43
HRAS	0.025	0.006	-10000	0	-10000	0	0
Syndecan-2/CASK	0.001	0.041	-10000	0	-0.25	13	13
ITGA5	0.017	0.043	-10000	0	-0.16	24	24
BAX	-0.001	0.037	-10000	0	-10000	0	0
EPB41	0.021	0.023	-10000	0	-0.28	2	2
positive regulation of cell-cell adhesion	0.016	0.04	-10000	0	-0.22	13	13
LAMA3	-0.004	0.1	-10000	0	-0.29	49	49
EZR	0.017	0.06	-10000	0	-0.43	9	9
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	0.013	0.041	-10000	0	-0.43	2	2
Syndecan-2/MMP2	0.01	0.06	-10000	0	-0.25	24	24
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.017	0.068	-10000	0	-0.3	19	19
dendrite morphogenesis	0.011	0.049	-10000	0	-0.24	16	16
Syndecan-2/GM-CSF	0.011	0.044	-10000	0	-0.25	13	13
determination of left/right symmetry	0.002	0.049	-10000	0	-0.3	13	13
Syndecan-2/PKC delta	0.005	0.081	-10000	0	-0.29	32	32
GNB2L1	0.026	0.004	-10000	0	-10000	0	0
MAPK3	0.02	0.066	0.19	49	-0.23	13	62
MAPK1	0.02	0.063	0.19	46	-0.23	11	57
Syndecan-2/RACK1	0.028	0.043	-10000	0	-0.21	13	13
NF1	0.025	0.02	-10000	0	-0.43	1	1
FGFR/FGF/Syndecan-2	0.002	0.049	-10000	0	-0.3	13	13
ITGA2	0.002	0.09	-10000	0	-0.43	19	19
MAPK8	-0.003	0.056	-10000	0	-0.25	25	25
Syndecan-2/alpha2/beta1 Integrin	0.008	0.11	0.19	1	-0.26	62	63
Syndecan-2/Kininogen	0.009	0.047	-10000	0	-0.25	13	13
ITGB1	0.023	0.012	-10000	0	-10000	0	0
SRC	0.025	0.064	0.19	50	-0.2	13	63
Syndecan-2/CASK/Protein 4.1	0.012	0.041	-10000	0	-0.21	15	15
extracellular matrix organization	0.013	0.045	-10000	0	-0.24	14	14
actin cytoskeleton reorganization	0.015	0.048	0.16	1	-0.25	13	14
Syndecan-2/Caveolin-2/Ras	0.023	0.046	-10000	0	-0.23	13	13
Syndecan-2/Laminin alpha3	0.002	0.077	0.16	1	-0.28	31	32
Syndecan-2/RasGAP	0.038	0.045	-10000	0	-0.2	13	13
alpha5/beta1 Integrin	0.029	0.034	-10000	0	-0.26	3	3
PRKCD	0.003	0.1	-10000	0	-0.43	26	26
Syndecan-2 dimer	0.011	0.049	-10000	0	-0.24	16	16
GO:0007205	0.002	0	-10000	0	-10000	0	0
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	0.027	0.045	0.18	9	-0.2	11	20
RHOA	0.026	0.004	-10000	0	-10000	0	0
SDCBP	0.025	0.006	-10000	0	-10000	0	0
TNFRSF13B	-0.003	0.028	-10000	0	-0.13	11	11
RASA1	0.026	0.003	-10000	0	-10000	0	0
alpha2/beta1 Integrin	0.017	0.068	-10000	0	-0.3	19	19
Syndecan-2/Synbindin	0.016	0.045	-10000	0	-0.25	13	13
TGFB1	0.021	0.022	-10000	0	-0.43	1	1
CASP3	0.013	0.089	0.19	46	-0.27	30	76
FN1	0.021	0.029	-10000	0	-10000	0	0
Syndecan-2/IL8	-0.028	0.099	0.17	4	-0.26	70	74
SDC2	0.002	0.049	-10000	0	-0.3	13	13
KNG1	-0.009	0.032	-10000	0	-0.13	22	22
Syndecan-2/Neurofibromin	0.018	0.045	-10000	0	-0.25	13	13
TRAPPC4	0.025	0.007	-10000	0	-10000	0	0
CSF2	-0.014	0.009	-10000	0	-10000	0	0
Syndecan-2/TGFB1	0.013	0.045	-10000	0	-0.24	14	14
Syndecan-2/Syntenin/PI-4-5-P2	0.016	0.041	-10000	0	-0.23	13	13
Syndecan-2/Ezrin	0.026	0.063	-10000	0	-0.29	17	17
PRKACA	0.025	0.066	0.19	48	-0.23	13	61
angiogenesis	-0.028	0.099	0.17	4	-0.26	70	74
MMP2	0.013	0.067	-10000	0	-0.26	24	24
IL8	-0.061	0.15	-10000	0	-0.25	158	158
calcineurin-NFAT signaling pathway	0.012	0.046	-10000	0	-0.24	14	14

×

Cellular roles of Anthrax 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.023	0.04	-10000	0	-0.43	4	4
ANTXR2	0.021	0.035	-10000	0	-0.19	11	11
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.001	0.006	-10000	0	-0.058	6	6
monocyte activation	-0.13	0.23	-10000	0	-0.42	176	176
MAP2K2	0.013	0.039	-10000	0	-0.61	2	2
MAP2K1	-0.003	0.007	-10000	0	-0.11	1	1
MAP2K7	-0.003	0.006	-10000	0	-10000	0	0
MAP2K6	-0.003	0.011	-10000	0	-0.22	1	1
CYAA	-0.007	0.023	-10000	0	-0.21	6	6
MAP2K4	-0.003	0.008	-10000	0	-0.11	2	2
IL1B	-0.043	0.079	0.17	2	-0.22	76	78
Channel	0.028	0.031	-10000	0	-0.23	6	6
NLRP1	-0.004	0.014	-10000	0	-0.22	2	2
CALM1	0.025	0.009	-10000	0	-0.13	1	1
negative regulation of phagocytosis	-0.004	0.078	-10000	0	-0.39	20	20
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.001	0.006	0.058	6	-10000	0	6
MAPK3	-0.003	0.006	-10000	0	-10000	0	0
MAPK1	-0.003	0.006	-10000	0	-10000	0	0
PGR	-0.022	0.061	-10000	0	-0.21	47	47
PA/Cellular Receptors	0.029	0.034	-10000	0	-0.25	6	6
apoptosis	-0.001	0.006	-10000	0	-0.058	6	6
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.029	0.027	-10000	0	-0.22	6	6
macrophage activation	-0.005	0.005	-10000	0	-10000	0	0
TNF	-0.06	0.16	-10000	0	-0.26	151	151
VCAM1	-0.13	0.23	-10000	0	-0.43	174	174
platelet activation	-0.004	0.078	-10000	0	-0.39	20	20
MAPKKK cascade	-0.005	0.024	0.091	1	-0.077	42	43
IL18	-0.012	0.051	0.16	3	-0.23	22	25
negative regulation of macrophage activation	-0.001	0.006	-10000	0	-0.058	6	6
LEF	-0.001	0.006	-10000	0	-0.058	6	6
CASP1	-0.001	0.018	-10000	0	-0.098	12	12
mol:cAMP	-0.005	0.079	-10000	0	-0.39	20	20
necrosis	-0.001	0.006	-10000	0	-0.058	6	6
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.028	0.029	-10000	0	-0.21	6	6
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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
HDAC1	0.022	0.01	-10000	0	-10000	0	0
HDAC3	0.026	0.004	-10000	0	-10000	0	0
VDR	-0.014	0.11	-10000	0	-0.26	71	71
Cbp/p300/PCAF	0.048	0.03	-10000	0	-0.26	4	4
EP300	0.022	0.04	-10000	0	-0.43	4	4
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.002	0.073	-10000	0	-0.37	10	10
KAT2B	0.025	0.008	-10000	0	-10000	0	0
MAPK14	0.026	0.003	-10000	0	-10000	0	0
AKT1	-0.012	0.075	0.2	6	-0.39	7	13
RAR alpha/9cRA/Cyclin H	-0.008	0.11	0.22	1	-0.38	11	12
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.002	0.062	0.18	1	-0.31	10	11
CDC2	0	0	-10000	0	-10000	0	0
response to UV	0.001	0	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.026	0.1	-10000	0	-0.4	18	18
NCOR2	0.026	0.003	-10000	0	-10000	0	0
VDR/VDR/Vit D3	-0.009	0.08	-10000	0	-0.29	33	33
RXRs/RARs/NRIP1/9cRA	-0.075	0.19	-10000	0	-0.56	32	32
NCOA2	-0.005	0.11	-10000	0	-0.43	34	34
NCOA3	0.025	0.005	-10000	0	-10000	0	0
NCOA1	0.026	0.003	-10000	0	-10000	0	0
VDR/VDR/DNA	-0.014	0.11	-10000	0	-0.26	71	71
RARG	0.026	0.008	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.034	0.009	-10000	0	-10000	0	0
MAPK3	0.027	0.002	-10000	0	-10000	0	0
MAPK1	0.026	0.003	-10000	0	-10000	0	0
MAPK8	0.014	0.071	-10000	0	-0.43	13	13
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.087	0.2	-10000	0	-0.45	90	90
RARA	-0.026	0.097	-10000	0	-0.24	75	75
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.012	0.089	0.18	1	-0.34	20	21
PRKCA	0.026	0.021	-10000	0	-0.43	1	1
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.08	0.2	-10000	0	-0.56	40	40
RXRG	-0.061	0.16	-10000	0	-0.38	93	93
RXRA	-0.022	0.088	-10000	0	-0.36	10	10
RXRB	-0.027	0.099	-10000	0	-0.28	65	65
VDR/Vit D3/DNA	-0.009	0.08	-10000	0	-0.29	33	33
RBP1	-0.006	0.082	-10000	0	-0.43	10	10
CRBP1/9-cic-RA	-0.002	0.056	-10000	0	-0.27	12	12
RARB	0.024	0.035	-10000	0	-0.43	3	3
PRKCG	-0.065	0.15	-10000	0	-0.26	159	159
MNAT1	0.025	0.005	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.08	0.19	-10000	0	-0.45	79	79
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.059	0.16	-10000	0	-0.47	32	32
proteasomal ubiquitin-dependent protein catabolic process	-0.013	0.096	0.21	2	-0.35	17	19
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.076	0.19	-10000	0	-0.59	32	32
positive regulation of DNA binding	-0.014	0.1	-10000	0	-0.36	11	11
NRIP1	-0.066	0.18	-10000	0	-0.66	13	13
RXRs/RARs	-0.076	0.2	-10000	0	-0.57	38	38
RXRs/RXRs/DNA/9cRA	-0.088	0.18	-10000	0	-0.44	86	86
PRKACA	0.025	0.005	-10000	0	-10000	0	0
CDK7	0.026	0.003	-10000	0	-10000	0	0
TFIIH	0.051	0.012	-10000	0	-10000	0	0
RAR alpha/9cRA	0.007	0.092	-10000	0	-0.31	9	9
CCNH	0.026	0.003	-10000	0	-10000	0	0
CREBBP	0.026	0.003	-10000	0	-10000	0	0
RAR gamma2/9cRA	0.047	0.017	-10000	0	-10000	0	0

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.022	0.14	-10000	0	-0.41	55	55
HRAS	0.025	0.006	-10000	0	-10000	0	0
EGFR	-0.016	0.12	-10000	0	-0.4	46	46
AKT	0.038	0.11	0.27	44	-0.28	4	48
FOXO3	0.025	0.005	-10000	0	-10000	0	0
AKT1	0.025	0.005	-10000	0	-10000	0	0
FOXO1	0.024	0.022	-10000	0	-0.28	2	2
AKT3	0.022	0.04	-10000	0	-0.43	4	4
FOXO4	0.025	0.02	-10000	0	-0.43	1	1
MET	-0.047	0.14	-10000	0	-0.43	52	52
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
PIK3CB	0.026	0.003	-10000	0	-10000	0	0
NRAS	0.021	0.01	-10000	0	-10000	0	0
PIK3CG	-0.01	0.1	-10000	0	-0.27	53	53
PIK3R3	0.02	0.024	-10000	0	-0.23	3	3
PIK3R2	0.025	0.005	-10000	0	-10000	0	0
NF1	0.025	0.02	-10000	0	-0.43	1	1
RAS	-0.008	0.07	0.16	3	-0.15	73	76
ERBB2	0.023	0.027	-10000	0	-0.17	8	8
proliferation/survival/translation	-0.025	0.081	0.31	16	-0.22	13	29
PI3K	0.021	0.11	0.25	61	-0.15	53	114
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
KRAS	0.025	0.005	-10000	0	-10000	0	0
FOXO	0.061	0.087	0.22	78	-10000	0	78
AKT2	0.022	0.01	-10000	0	-10000	0	0
PTEN	0.025	0.006	-10000	0	-10000	0	0

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0.008	0.086	-10000	0	-0.22	58	58
MAPK9	0.007	0.001	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.058	0.11	-10000	0	-0.3	79	79
GNB1/GNG2	0.027	0.028	-10000	0	-0.26	4	4
GNB1	0.022	0.01	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.007	0.001	-10000	0	-10000	0	0
Gs family/GTP	-0.012	0.079	-10000	0	-0.23	61	61
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	0.008	0.02	0.062	61	-10000	0	61
GNAL	-0.028	0.15	-10000	0	-0.42	61	61
GNG2	0.022	0.04	-10000	0	-0.43	4	4
CRH	-0.075	0.16	-10000	0	-0.43	79	79
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	-0.001	0.047	-10000	0	-0.3	13	13
MAPK11	0.002	0.037	-10000	0	-0.3	8	8

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0.002	0.053	0.19	1	-0.29	3	4
adherens junction organization	-0.019	0.09	-10000	0	-0.25	56	56
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.003	0.082	-10000	0	-0.29	8	8
FMN1	-0.032	0.11	-10000	0	-0.27	60	60
mol:IP3	0.004	0.053	-10000	0	-0.23	4	4
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.007	0.09	-10000	0	-0.24	56	56
CTNNB1	0.027	0.005	-10000	0	-10000	0	0
AKT1	0.008	0.064	0.18	2	-0.27	4	6
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.013	0.13	-10000	0	-0.36	55	55
CTNND1	0.026	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.009	0.083	-10000	0	-0.23	55	55
VASP	-0.011	0.081	-10000	0	-0.24	40	40
ZYX	-0.012	0.078	-10000	0	-0.24	48	48
JUB	-0.009	0.085	-10000	0	-0.23	56	56
EGFR(dimer)	-0.017	0.1	-10000	0	-0.25	56	56
E-cadherin/beta catenin-gamma catenin	-0.001	0.1	-10000	0	-0.25	63	63
mol:PI-3-4-5-P3	0.024	0.074	0.21	2	-0.28	4	6
PIK3CA	0.026	0.02	-10000	0	-0.41	1	1
PI3K	0.024	0.075	0.21	2	-0.29	4	6
FYN	0.002	0.05	-10000	0	-0.26	5	5
mol:Ca2+	0.004	0.052	-10000	0	-0.23	4	4
JUP	0.021	0.05	-10000	0	-0.39	7	7
PIK3R1	0.027	0.004	-10000	0	-10000	0	0
mol:DAG	0.004	0.053	-10000	0	-0.23	4	4
CDH1	-0.046	0.15	-10000	0	-0.43	59	59
RhoA/GDP	0.011	0.094	0.22	4	-0.29	8	12
establishment of polarity of embryonic epithelium	-0.011	0.08	-10000	0	-0.23	40	40
SRC	0.025	0.005	-10000	0	-10000	0	0
RAC1	0.023	0.009	-10000	0	-10000	0	0
RHOA	0.026	0.004	-10000	0	-10000	0	0
EGFR	-0.016	0.12	-10000	0	-0.4	46	46
CASR	-0.005	0.049	-10000	0	-0.24	2	2
RhoA/GTP	0.016	0.053	-10000	0	-0.3	1	1
AKT2	0.01	0.056	0.18	2	-0.26	4	6
actin cable formation	-0.03	0.098	0.18	1	-0.28	45	46
apoptosis	-0.003	0.064	0.28	5	-0.2	4	9
CTNNA1	0.026	0.005	-10000	0	-10000	0	0
mol:GDP	-0.017	0.076	0.15	5	-0.27	12	17
PIP5K1A	-0.01	0.084	-10000	0	-0.23	55	55
PLCG1	0.004	0.053	-10000	0	-0.24	4	4
Rac1/GTP	-0.007	0.1	-10000	0	-0.33	12	12
homophilic cell adhesion	0	0.002	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.022	0.04	-10000	0	-0.43	4	4
HDAC4	0.025	0.005	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.012	0.025	-10000	0	-0.13	18	18
CDKN1A	-0.034	0.13	-10000	0	-0.65	20	20
KAT2B	0.025	0.008	-10000	0	-10000	0	0
BAX	0.021	0.01	-10000	0	-10000	0	0
FOXO3	-0.003	0.033	0.36	4	-10000	0	4
FOXO1	0.024	0.022	-10000	0	-0.28	2	2
FOXO4	0.013	0.026	-10000	0	-0.25	5	5
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.026	0.004	-10000	0	-10000	0	0
TAT	-0.025	0.12	-10000	0	-0.26	88	88
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.064	0.12	-10000	0	-0.3	93	93
PPARGC1A	0.009	0.082	-10000	0	-0.37	21	21
FHL2	0.006	0.077	-10000	0	-0.22	43	43
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.04	0.025	-10000	0	-10000	0	0
HIST2H4A	0.012	0.025	0.13	18	-10000	0	18
SIRT1/FOXO3a	0.02	0.038	0.17	20	-0.19	4	24
SIRT1	0.03	0.033	0.2	18	-10000	0	18
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.05	0.028	-10000	0	-10000	0	0
SIRT1/Histone H1b	0.022	0.057	0.23	1	-0.22	19	20
apoptosis	-0.045	0.031	-10000	0	-10000	0	0
SIRT1/PGC1A	0.025	0.057	0.14	17	-0.25	17	34
p53/SIRT1	0.037	0.085	0.39	18	-0.31	12	30
SIRT1/FOXO4	0.031	0.037	0.16	18	-0.22	5	23
FOXO1/FHL2/SIRT1	0.042	0.05	-10000	0	-0.23	13	13
HIST1H1E	0.004	0.05	-10000	0	-0.24	20	20
SIRT1/p300	0.037	0.039	0.16	18	-0.31	4	22
muscle cell differentiation	0.03	0.12	0.25	93	-0.22	10	103
TP53	0.02	0.077	0.2	19	-0.43	12	31
KU70/SIRT1/BAX	0.045	0.031	-10000	0	-10000	0	0
CREBBP	0.026	0.003	-10000	0	-10000	0	0
MEF2D	0.025	0.011	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.003	0.097	0.18	1	-0.3	38	39
ACSS2	0.013	0.024	0.13	18	-10000	0	18
SIRT1/PCAF/MYOD	-0.03	0.12	0.22	10	-0.25	93	103

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.026	0.008	-10000	0	-0.13	1	1
RAS family/GTP/Tiam1	0.016	0.023	-10000	0	-0.26	2	2
NT3 (dimer)/TRKC	0.028	0.033	-10000	0	-0.34	2	2
NT3 (dimer)/TRKB	0.01	0.098	-10000	0	-0.26	55	55
SHC/Grb2/SOS1/GAB1/PI3K	0.027	0.026	-10000	0	-0.48	1	1
RAPGEF1	0.025	0.005	-10000	0	-10000	0	0
BDNF	-0.01	0.089	-10000	0	-0.43	14	14
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
DYNLT1	0.024	0.029	-10000	0	-0.43	2	2
NTRK1	0.016	0.055	-10000	0	-0.22	20	20
NTRK2	0.006	0.092	-10000	0	-0.43	22	22
NTRK3	0.022	0.04	-10000	0	-0.43	4	4
NT-4/5 (dimer)/TRKB	0.004	0.093	-10000	0	-0.25	52	52
neuron apoptosis	0.057	0.15	0.36	75	-10000	0	75
SHC 2-3/Grb2	-0.062	0.16	-10000	0	-0.39	75	75
SHC1	0.024	0.014	-10000	0	-10000	0	0
SHC2	-0.029	0.1	-10000	0	-0.41	13	13
SHC3	-0.099	0.21	-10000	0	-0.52	84	84
STAT3 (dimer)	0.021	0.055	-10000	0	-0.33	11	11
NT3 (dimer)/TRKA	0.018	0.087	-10000	0	-0.25	46	46
RIN/GDP	-0.004	0.081	0.23	6	-0.3	2	8
GIPC1	0.025	0.009	-10000	0	-0.13	1	1
KRAS	0.025	0.005	-10000	0	-10000	0	0
DNAJA3	-0.047	0.099	-10000	0	-0.26	76	76
RIN/GTP	-0.072	0.13	-10000	0	-0.3	119	119
CCND1	0.002	0.11	-10000	0	-0.7	11	11
MAGED1	0.026	0.002	-10000	0	-10000	0	0
PTPN11	0.026	0.003	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.003	0.033	-10000	0	-0.16	12	12
SHC/GRB2/SOS1	0.05	0.014	-10000	0	-10000	0	0
GRB2	0.025	0.006	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.014	0.12	-10000	0	-0.28	83	83
TRKA/NEDD4-2	0.025	0.054	-10000	0	-0.31	10	10
ELMO1	0.017	0.049	-10000	0	-0.43	6	6
RhoG/GTP/ELMO1/DOCK1	0.024	0.038	-10000	0	-0.25	8	8
NGF	-0.025	0.13	-10000	0	-0.43	46	46
HRAS	0.025	0.006	-10000	0	-10000	0	0
DOCK1	0.022	0.035	-10000	0	-0.43	3	3
GAB2	0.025	0.005	-10000	0	-10000	0	0
RIT2	-0.11	0.19	-10000	0	-0.43	119	119
RIT1	0.026	0.004	-10000	0	-10000	0	0
FRS2	0.026	0.004	-10000	0	-10000	0	0
DNM1	-0.027	0.12	-10000	0	-0.22	108	108
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.026	0.002	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.032	0.1	-10000	0	-0.25	71	71
mol:GDP	0.03	0.073	0.27	8	-0.62	1	9
NGF (dimer)	-0.025	0.13	-10000	0	-0.43	46	46
RhoG/GDP	0.013	0.035	-10000	0	-0.3	6	6
RIT1/GDP	0.027	0.053	0.2	4	-0.37	1	5
TIAM1	0.026	0.004	-10000	0	-10000	0	0
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	0.03	0.083	-10000	0	-0.26	36	36
KIDINS220/CRKL/C3G	0.037	0.01	-10000	0	-10000	0	0
SHC/RasGAP	0.037	0.013	-10000	0	-10000	0	0
FRS2 family/SHP2	0.052	0.01	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0.061	0.024	-10000	0	-0.24	1	1
RIT1/GTP	0.019	0.003	-10000	0	-10000	0	0
NT3 (dimer)	0.006	0.032	-10000	0	-10000	0	0
RAP1/GDP	0.023	0.04	-10000	0	-0.31	1	1
KIDINS220/CRKL	0.025	0.008	-10000	0	-0.13	1	1
BDNF (dimer)	-0.01	0.089	-10000	0	-0.43	14	14
ubiquitin-dependent protein catabolic process	-0.001	0.098	-10000	0	-0.26	55	55
Schwann cell development	-0.014	0.019	-10000	0	-10000	0	0
EHD4	0.024	0.019	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.063	0.018	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.033	0.03	-10000	0	-0.42	1	1
RAP1B	0.026	0.004	-10000	0	-10000	0	0
RAP1A	0.021	0.01	-10000	0	-10000	0	0
CDC42/GTP	0.016	0.069	-10000	0	-0.22	27	27
ABL1	0.025	0.005	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.037	0.009	-10000	0	-10000	0	0
Rap1/GTP	-0.008	0.089	-10000	0	-0.32	9	9
STAT3	0.021	0.055	-10000	0	-0.33	11	11
axon guidance	-0.002	0.064	-10000	0	-0.22	27	27
MAPK3	-0.037	0.11	0.18	11	-0.26	78	89
MAPK1	-0.036	0.11	0.18	11	-0.26	77	88
CDC42/GDP	0.032	0.052	0.22	6	-0.37	1	7
NTF3	0.006	0.032	-10000	0	-10000	0	0
NTF4	-0.003	0.033	-10000	0	-0.16	12	12
NGF (dimer)/TRKA/FAIM	0.008	0.096	-10000	0	-0.26	55	55
PI3K	0.038	0.007	-10000	0	-10000	0	0
FRS3	0.026	0.002	-10000	0	-10000	0	0
FAIM	0.022	0.04	-10000	0	-0.43	4	4
GAB1	0.025	0.02	-10000	0	-0.43	1	1
RASGRF1	-0.07	0.12	-10000	0	-0.26	121	121
SOS1	0.026	0.002	-10000	0	-10000	0	0
MCF2L	0.002	0.028	-10000	0	-0.28	3	3
RGS19	0.025	0.005	-10000	0	-10000	0	0
CDC42	0.022	0.01	-10000	0	-10000	0	0
RAS family/GTP	0.002	0.069	-10000	0	-0.61	2	2
Rac1/GDP	0.025	0.053	0.22	5	-0.36	1	6
NGF (dimer)/TRKA/GRIT	-0.008	0.088	-10000	0	-0.25	53	53
neuron projection morphogenesis	-0.029	0.12	0.35	1	-0.53	7	8
NGF (dimer)/TRKA/NEDD4-2	0.006	0.098	-10000	0	-0.25	59	59
MAP2K1	0.024	0.05	0.2	35	-0.23	1	36
NGFR	-0.017	0.12	-10000	0	-0.28	72	72
NGF (dimer)/TRKA/GIPC/GAIP	-0.023	0.096	-10000	0	-0.24	73	73
RAS family/GTP/PI3K	0.019	0.013	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	0.072	0.022	-10000	0	-10000	0	0
NRAS	0.021	0.01	-10000	0	-10000	0	0
GRB2/SOS1	0.037	0.009	-10000	0	-10000	0	0
PRKCI	0.026	0.003	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.023	0.009	-10000	0	-10000	0	0
PRKCZ	0.007	0.076	-10000	0	-0.43	14	14
MAPKKK cascade	-0.11	0.23	-10000	0	-0.47	135	135
RASA1	0.026	0.003	-10000	0	-10000	0	0
TRKA/c-Abl	0.029	0.042	-10000	0	-0.3	6	6
SQSTM1	0.026	0.004	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	0.043	0.075	-10000	0	-0.25	27	27
NGF (dimer)/TRKA/p62/Atypical PKCs	0.022	0.1	-10000	0	-0.24	58	58
MATK	-0.027	0.13	-10000	0	-0.43	46	46
NEDD4L	0.02	0.044	-10000	0	-0.43	4	4
RAS family/GDP	-0.006	0.02	-10000	0	-0.28	1	1
NGF (dimer)/TRKA	-0.035	0.11	-10000	0	-0.27	76	76
Rac1/GTP	-0.04	0.077	-10000	0	-0.25	27	27
FRS2 family/SHP2/CRK family	0.074	0.018	-10000	0	-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	0.021	0.022	-10000	0	-0.43	1	1
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.001	0.088	0.38	4	-0.48	2	6
IL27/IL27R/JAK1	0.022	0.12	0.88	2	-10000	0	2
TBX21	-0.019	0.16	0.46	14	-0.4	19	33
IL12B	-0.001	0.024	-10000	0	-0.13	6	6
IL12A	-0.008	0.065	-10000	0	-0.3	23	23
IL6ST	-0.002	0.11	-10000	0	-0.43	32	32
IL27RA/JAK1	0.024	0.051	-10000	0	-10000	0	0
IL27	0.014	0.038	-10000	0	-0.13	24	24
TYK2	0.025	0.007	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.01	0.12	0.43	1	-0.5	3	4
T-helper 2 cell differentiation	0.001	0.088	0.38	4	-0.48	2	6
T cell proliferation during immune response	0.001	0.088	0.38	4	-0.48	2	6
MAPKKK cascade	-0.001	0.088	0.48	2	-0.38	4	6
STAT3	0.026	0.003	-10000	0	-10000	0	0
STAT2	0.025	0.014	-10000	0	-0.13	4	4
STAT1	0.021	0.029	-10000	0	-0.13	16	16
IL12RB1	-0.001	0.098	-10000	0	-0.31	39	39
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.034	0.16	0.45	13	-0.4	29	42
IL27/IL27R/JAK2/TYK2	-0.001	0.089	0.48	2	-0.38	4	6
positive regulation of T cell mediated cytotoxicity	-0.001	0.088	0.48	2	-0.38	4	6
STAT1 (dimer)	0.009	0.19	0.56	26	-0.48	4	30
JAK2	0.025	0.007	-10000	0	-10000	0	0
JAK1	0.021	0.012	-10000	0	-10000	0	0
STAT2 (dimer)	0.018	0.097	0.39	3	-0.37	3	6
T cell proliferation	-0.021	0.1	0.44	2	-0.39	7	9
IL12/IL12R/TYK2/JAK2	0.001	0.13	-10000	0	-0.78	10	10
IL17A	-0.009	0.11	0.43	1	-0.47	2	3
mast cell activation	0.001	0.088	0.38	4	-0.48	2	6
IFNG	0.005	0.026	0.12	4	-0.11	5	9
T cell differentiation	-0.002	0.004	-10000	0	-0.015	6	6
STAT3 (dimer)	0.018	0.098	0.39	3	-0.36	4	7
STAT5A (dimer)	0.013	0.11	0.39	3	-0.42	7	10
STAT4 (dimer)	-0.011	0.13	0.39	3	-0.4	12	15
STAT4	-0.064	0.16	-10000	0	-0.26	162	162
T cell activation	-0.006	0.003	-10000	0	-10000	0	0
IL27R/JAK2/TYK2	0.025	0.074	-10000	0	-10000	0	0
GATA3	-0.085	0.44	0.62	39	-1.3	49	88
IL18	-0.009	0.063	-10000	0	-0.2	39	39
positive regulation of mast cell cytokine production	0.018	0.096	0.39	3	-0.36	4	7
IL27/EBI3	0.019	0.067	0.24	2	-0.28	18	20
IL27RA	0.009	0.033	-10000	0	-10000	0	0
IL6	-0.035	0.12	-10000	0	-0.43	37	37
STAT5A	0.016	0.066	-10000	0	-0.43	11	11
monocyte differentiation	0	0	-10000	0	-10000	0	0
IL2	-0.015	0.023	-10000	0	-10000	0	0
IL1B	-0.056	0.11	-10000	0	-0.18	173	173
EBI3	0.011	0.078	-10000	0	-0.38	18	18
TNF	-0.049	0.1	-10000	0	-0.3	68	68

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.023	0.042	-10000	0	-0.25	5	5
PDGFRB	0.025	0.013	-10000	0	-0.14	2	2
SPHK1	-0.02	0.14	-10000	0	-0.72	19	19
mol:S1P	-0.019	0.13	-10000	0	-0.63	19	19
S1P1/S1P/Gi	-0.028	0.13	-10000	0	-0.35	59	59
GNAO1	0.017	0.047	-10000	0	-0.43	5	5
PDGFB-D/PDGFRB/PLCgamma1	-0.014	0.13	0.28	10	-0.34	52	62
PLCG1	-0.027	0.12	-10000	0	-0.34	57	57
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.025	0.013	-10000	0	-0.14	2	2
GNAI2	0.021	0.016	-10000	0	-10000	0	0
GNAI3	0.018	0.015	-10000	0	-10000	0	0
GNAI1	0.015	0.038	-10000	0	-0.43	3	3
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	-0.005	0.028	-10000	0	-0.2	5	5
S1P1/S1P	-0.016	0.1	-10000	0	-0.47	18	18
negative regulation of cAMP metabolic process	-0.027	0.13	-10000	0	-0.34	59	59
MAPK3	-0.05	0.18	-10000	0	-0.53	59	59
calcium-dependent phospholipase C activity	-0.001	0.003	-10000	0	-10000	0	0
Rac1/GDP	0.017	0.007	-10000	0	-10000	0	0
RhoA/GDP	0.019	0.003	-10000	0	-10000	0	0
KDR	0.017	0.04	-10000	0	-0.23	9	9
PLCB2	-0.012	0.11	0.31	3	-0.44	19	22
RAC1	0.023	0.009	-10000	0	-10000	0	0
RhoA/GTP	-0.014	0.087	-10000	0	-0.4	18	18
receptor internalization	-0.016	0.096	-10000	0	-0.42	19	19
PTGS2	-0.095	0.33	-10000	0	-1	58	58
Rac1/GTP	-0.015	0.083	-10000	0	-0.38	17	17
RHOA	0.026	0.004	-10000	0	-10000	0	0
VEGFA	0.016	0.034	-10000	0	-0.13	21	21
negative regulation of T cell proliferation	-0.027	0.13	-10000	0	-0.34	59	59
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	0.021	0.016	-10000	0	-10000	0	0
MAPK1	-0.051	0.18	-10000	0	-0.53	60	60
S1P1/S1P/PDGFB-D/PDGFRB	-0.006	0.1	0.22	1	-0.4	18	19
ABCC1	0.025	0.015	-10000	0	-0.14	4	4

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.032	0.13	-10000	0	-0.49	18	18
UGCG	-0.018	0.15	-10000	0	-0.69	22	22
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.037	0.15	0.23	2	-0.4	37	39
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.018	0.14	-10000	0	-0.68	22	22
mol:DAG	-0.016	0.16	-10000	0	-0.82	18	18
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.018	0.15	0.25	1	-0.42	36	37
FRAP1	-0.028	0.17	0.27	2	-0.48	37	39
FOXO3	-0.027	0.15	0.27	2	-0.42	41	43
AKT1	-0.029	0.16	0.28	1	-0.45	42	43
GAB2	0.025	0.006	-10000	0	-10000	0	0
SMPD1	-0.013	0.12	-10000	0	-0.58	21	21
SGMS1	-0.008	0.11	-10000	0	-0.56	18	18
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	0.005	0.008	-10000	0	-10000	0	0
CALM1	0.025	0.009	-10000	0	-0.13	1	1
cell proliferation	-0.011	0.14	0.25	3	-0.46	19	22
EIF3A	0.025	0.007	-10000	0	-10000	0	0
PI3K	0.039	0.012	-10000	0	-10000	0	0
RPS6KB1	0.002	0.076	-10000	0	-1.1	1	1
mol:sphingomyelin	-0.016	0.16	-10000	0	-0.82	18	18
natural killer cell activation	0	0.002	-10000	0	-0.011	14	14
JAK3	-0.008	0.1	-10000	0	-0.24	65	65
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
JAK1	0.023	0.011	-10000	0	-10000	0	0
NFKB1	0.026	0.004	-10000	0	-10000	0	0
MYC	-0.025	0.24	0.35	4	-0.84	28	32
MYB	-0.075	0.33	-10000	0	-1.1	42	42
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.027	0.14	-10000	0	-0.39	36	36
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.025	0.078	-10000	0	-1	1	1
mol:PI-3-4-5-P3	-0.026	0.13	-10000	0	-0.38	36	36
Rac1/GDP	0.019	0.013	-10000	0	-10000	0	0
T cell proliferation	-0.018	0.12	0.22	1	-0.38	27	28
SHC1	0.024	0.015	-10000	0	-10000	0	0
RAC1	0.023	0.009	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	-0.002	0.018	-10000	0	-0.064	38	38
PRKCZ	-0.015	0.12	0.22	1	-0.4	26	27
NF kappa B1 p50/RelA	-0.009	0.15	0.27	2	-0.43	33	35
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.033	0.14	-10000	0	-0.42	44	44
HSP90AA1	0.025	0.005	-10000	0	-10000	0	0
RELA	0.025	0.005	-10000	0	-10000	0	0
IL2RA	-0.007	0.072	-10000	0	-0.43	8	8
IL2RB	-0.027	0.13	-10000	0	-0.43	39	39
TERT	-0.042	0.13	-10000	0	-0.32	74	74
E2F1	-0.014	0.13	-10000	0	-0.45	42	42
SOS1	0.026	0.004	-10000	0	-10000	0	0
RPS6	0.024	0.01	-10000	0	-0.13	1	1
mol:cAMP	0.001	0.009	0.031	38	-10000	0	38
PTPN11	0.025	0.008	-10000	0	-10000	0	0
IL2RG	0.001	0.087	-10000	0	-0.22	52	52
actin cytoskeleton organization	-0.018	0.12	0.22	1	-0.38	27	28
GRB2	0.025	0.007	-10000	0	-10000	0	0
IL2	0.013	0.013	-10000	0	-10000	0	0
PIK3CA	0.026	0.021	-10000	0	-0.43	1	1
Rac1/GTP	0.041	0.025	-10000	0	-10000	0	0
LCK	-0.019	0.11	-10000	0	-0.43	30	30
BCL2	-0.023	0.16	-10000	0	-0.63	17	17

×

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

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
MAP4K1	-0.002	0.099	0.22	12	-0.41	18	30
CRKL	0	0.098	-10000	0	-0.43	20	20
HRAS	0.007	0.11	-10000	0	-0.38	20	20
mol:PIP3	0.012	0.1	0.31	7	-0.38	18	25
SPRED1	0.026	0.003	-10000	0	-10000	0	0
SPRED2	0.025	0.012	-10000	0	-0.13	3	3
GAB1	0.002	0.1	0.2	2	-0.44	21	23
FOXO3	0.017	0.13	0.29	8	-0.41	25	33
AKT1	0.018	0.14	0.3	10	-0.43	29	39
BAD	0.021	0.14	0.32	10	-0.41	27	37
megakaryocyte differentiation	0	0.1	0.2	3	-0.42	22	25
GSK3B	0.017	0.13	0.31	9	-0.41	26	35
RAF1	0.006	0.094	0.25	1	-0.32	16	17
SHC1	0.024	0.014	-10000	0	-10000	0	0
STAT3	0.004	0.1	0.2	3	-0.43	21	24
STAT1	-0.013	0.22	-10000	0	-0.89	28	28
HRAS/SPRED1	0.018	0.099	0.25	1	-0.33	16	17
cell proliferation	-0.003	0.11	0.2	3	-0.45	22	25
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
TEC	0.015	0.063	-10000	0	-0.29	17	17
RPS6KB1	0.014	0.12	0.26	4	-0.44	23	27
HRAS/SPRED2	0.018	0.099	0.25	1	-0.33	16	17
LYN/TEC/p62DOK	0.029	0.12	-10000	0	-0.43	23	23
MAPK3	0.014	0.082	0.22	18	-0.29	6	24
STAP1	-0.001	0.1	-10000	0	-0.42	23	23
GRAP2	-0.007	0.1	-10000	0	-0.43	25	25
JAK2	-0.014	0.2	-10000	0	-0.77	28	28
STAT1 (dimer)	-0.011	0.22	-10000	0	-0.87	28	28
mol:Gleevec	-0.001	0.004	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	0.023	0.12	-10000	0	-0.42	25	25
actin filament polymerization	-0.005	0.099	0.32	5	-0.4	21	26
LYN	0.021	0.035	-10000	0	-0.43	2	2
STAP1/STAT5A (dimer)	-0.011	0.16	-10000	0	-0.61	27	27
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
CBL/CRKL/GRB2	0.021	0.099	-10000	0	-0.4	19	19
PI3K	0.036	0.12	0.27	3	-0.42	20	23
PTEN	0.025	0.006	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.007	0.25	-10000	0	-1.2	20	20
MAPK8	-0.003	0.11	0.2	3	-0.46	22	25
STAT3 (dimer)	0.004	0.1	0.2	3	-0.42	21	24
positive regulation of transcription	0.015	0.071	0.2	20	-0.23	6	26
mol:GDP	0.003	0.11	-10000	0	-0.39	22	22
PIK3C2B	0.002	0.1	0.2	3	-0.42	21	24
CBL/CRKL	0.011	0.099	-10000	0	-0.41	19	19
FER	-0.005	0.12	0.2	3	-0.45	24	27
SH2B3	0.003	0.1	0.2	3	-0.43	21	24
PDPK1	0.011	0.1	0.32	8	-0.38	17	25
SNAI2	-0.003	0.11	0.29	2	-0.42	25	27
positive regulation of cell proliferation	-0.007	0.18	-10000	0	-0.71	27	27
KITLG	0.017	0.066	-10000	0	-0.44	10	10
cell motility	-0.007	0.18	-10000	0	-0.71	27	27
PTPN6	0.013	0.063	-10000	0	-0.42	10	10
EPOR	0.031	0.084	-10000	0	-1.2	1	1
STAT5A (dimer)	-0.004	0.16	-10000	0	-0.59	29	29
SOCS1	0.008	0.068	-10000	0	-0.43	8	8
cell migration	0.017	0.11	0.42	25	-0.2	2	27
SOS1	0.026	0.002	-10000	0	-10000	0	0
EPO	0.016	0.03	-10000	0	-0.24	3	3
VAV1	0.005	0.09	-10000	0	-0.34	29	29
GRB10	-0.001	0.094	0.24	1	-0.41	20	21
PTPN11	0.025	0.006	-10000	0	-10000	0	0
SCF/KIT	0.006	0.11	0.21	3	-0.45	21	24
GO:0007205	0	0.005	-10000	0	-10000	0	0
MAP2K1	0.008	0.081	0.22	5	-0.26	15	20
CBL	0.025	0.007	-10000	0	-10000	0	0
KIT	-0.012	0.26	-10000	0	-1.2	20	20
MAP2K2	0.013	0.086	0.26	16	-0.26	14	30
SHC/Grb2/SOS1	0.037	0.11	-10000	0	-0.42	19	19
STAT5A	-0.004	0.16	-10000	0	-0.61	29	29
GRB2	0.025	0.006	-10000	0	-10000	0	0
response to radiation	-0.002	0.1	0.28	2	-0.41	25	27
SHC/GRAP2	0.012	0.079	-10000	0	-0.3	26	26
PTPRO	0	0.1	0.2	3	-0.42	22	25
SH2B2	-0.007	0.096	0.23	2	-0.4	21	23
DOK1	0.025	0.021	-10000	0	-0.28	2	2
MATK	-0.017	0.11	0.2	2	-0.43	25	27
CREBBP	0.034	0.033	-10000	0	-10000	0	0
BCL2	0.012	0.19	-10000	0	-1.4	8	8

×

Signaling events mediated by PTP1B

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
PDGFRB	0.025	0.013	-10000	0	-10000	0	0
Jak2/Leptin Receptor	0.006	0.12	0.24	3	-0.38	31	34
PTP1B/AKT1	0.013	0.092	0.2	4	-0.33	11	15
FYN	0.025	0.005	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	0.003	0.094	0.21	5	-0.32	15	20
EGFR	-0.019	0.13	-10000	0	-0.42	45	45
EGF/EGFR	-0.018	0.12	-10000	0	-0.29	65	65
CSF1	0.017	0.045	-10000	0	-0.43	5	5
AKT1	0.026	0.006	-10000	0	-10000	0	0
INSR	0.025	0.006	-10000	0	-10000	0	0
PTP1B/N-cadherin	0.013	0.096	0.21	4	-0.32	15	19
Insulin Receptor/Insulin	0.018	0.087	-10000	0	-0.41	6	6
HCK	0.014	0.063	-10000	0	-0.27	19	19
CRK	0.026	0.002	-10000	0	-10000	0	0
TYK2	0.008	0.1	0.3	20	-0.32	13	33
EGF	-0.012	0.12	-10000	0	-0.43	34	34
YES1	0.022	0.04	-10000	0	-0.43	4	4
CAV1	0.017	0.12	0.25	38	-0.32	19	57
TXN	0.026	0.006	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	0.021	0.094	0.22	1	-0.34	10	11
cell migration	-0.003	0.094	0.32	15	-0.21	5	20
STAT3	0.026	0.003	-10000	0	-10000	0	0
PRLR	0.007	0.088	-10000	0	-0.43	19	19
ITGA2B	-0.012	0.12	-10000	0	-0.43	40	40
CSF1R	0.002	0.099	-10000	0	-0.43	25	25
Prolactin Receptor/Prolactin	0.02	0.066	-10000	0	-0.31	18	18
FGR	0.021	0.015	-10000	0	-0.13	3	3
PTP1B/p130 Cas	0.012	0.095	0.21	4	-0.31	15	19
Crk/p130 Cas	0.023	0.097	0.22	2	-0.33	11	13
DOK1	0.008	0.093	0.21	11	-0.38	9	20
JAK2	0.001	0.13	0.21	1	-0.39	33	34
Jak2/Leptin Receptor/Leptin	-0.019	0.1	-10000	0	-0.32	23	23
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
PTPN1	0.003	0.095	0.21	5	-0.32	15	20
LYN	0.021	0.035	-10000	0	-0.43	2	2
CDH2	0.025	0.02	-10000	0	-0.43	1	1
SRC	0.024	0.052	-10000	0	-0.37	4	4
ITGB3	-0.001	0.082	-10000	0	-0.19	64	64
CAT1/PTP1B	-0.015	0.16	0.28	37	-0.37	42	79
CAPN1	0.025	0.021	-10000	0	-0.43	1	1
CSK	0.026	0.003	-10000	0	-10000	0	0
PI3K	0.027	0.085	-10000	0	-0.42	5	5
mol:H2O2	0.001	0.004	-10000	0	-10000	0	0
STAT3 (dimer)	-0.02	0.099	-10000	0	-0.34	22	22
negative regulation of transcription	0.001	0.12	0.21	1	-0.38	33	34
FCGR2A	0.001	0.092	-10000	0	-0.43	20	20
FER	0.008	0.09	-10000	0	-0.42	21	21
alphaIIb/beta3 Integrin	-0.01	0.11	-10000	0	-0.31	53	53
BLK	-0.03	0.11	-10000	0	-0.43	29	29
Insulin Receptor/Insulin/Shc	0.039	0.031	-10000	0	-0.26	4	4
RHOA	0.027	0.005	-10000	0	-10000	0	0
LEPR	0.017	0.04	-10000	0	-0.42	3	3
BCAR1	0.025	0.02	-10000	0	-0.43	1	1
p210 bcr-abl/Grb2	0.025	0.006	-10000	0	-10000	0	0
mol:NADPH	0.001	0.004	-10000	0	-10000	0	0
TRPV6	-0.032	0.17	0.26	19	-0.42	45	64
PRL	0.003	0.02	-10000	0	-10000	0	0
SOCS3	-0.072	0.31	-10000	0	-1.3	33	33
SPRY2	0.024	0.028	-10000	0	-0.18	6	6
Insulin Receptor/Insulin/IRS1	0.04	0.03	-10000	0	-0.26	4	4
CSF1/CSF1R	0.005	0.11	0.22	2	-0.31	26	28
Ras protein signal transduction	0.018	0.12	0.51	24	-10000	0	24
IRS1	0.026	0.003	-10000	0	-10000	0	0
INS	0.005	0.042	-10000	0	-0.43	4	4
LEP	0.007	0.02	-10000	0	-0.13	4	4
STAT5B	0.009	0.1	0.2	5	-0.33	17	22
STAT5A	0.005	0.11	0.21	4	-0.34	18	22
GRB2	0.025	0.006	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.013	0.095	0.2	3	-0.3	15	18
CSN2	-0.01	0.06	-10000	0	-0.56	2	2
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
LAT	-0.015	0.14	-10000	0	-0.45	46	46
YBX1	0.026	0.031	-10000	0	-0.42	2	2
LCK	-0.019	0.11	-10000	0	-0.43	30	30
SHC1	0.024	0.014	-10000	0	-10000	0	0
NOX4	-0.009	0.1	-10000	0	-0.42	23	23

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.06	0.08	0.36	1	-0.48	4	5
CRKL	0.052	0.081	0.23	38	-0.38	1	39
mol:DAG	0.028	0.049	-10000	0	-0.35	3	3
HRAS	0.049	0.086	0.27	36	-0.3	1	37
MAPK8	0.032	0.071	0.16	79	-0.24	12	91
RAP1A	0.047	0.08	0.24	39	-0.36	1	40
GAB1	0.051	0.083	0.28	23	-0.35	2	25
MAPK14	0.04	0.063	0.16	88	-0.26	2	90
EPO	0.019	0.03	-10000	0	-0.46	1	1
PLCG1	0.028	0.05	-10000	0	-0.36	3	3
EPOR/TRPC2/IP3 Receptors	0.029	0.013	-10000	0	-10000	0	0
RAPGEF1	0.025	0.005	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.024	0.075	-10000	0	-0.27	23	23
GAB1/SHC/GRB2/SOS1	0.07	0.073	0.26	21	-0.33	2	23
EPO/EPOR (dimer)	0.031	0.03	-10000	0	-0.34	1	1
IRS2	0.049	0.081	0.28	19	-0.35	2	21
STAT1	0.035	0.059	-10000	0	-0.35	5	5
STAT5B	0.03	0.053	-10000	0	-0.34	4	4
cell proliferation	0.028	0.095	0.2	100	-0.23	11	111
GAB1/SHIP/PIK3R1/SHP2/SHC	0.047	0.056	0.22	1	-0.33	3	4
TEC	0.047	0.085	0.24	36	-0.24	6	42
SOCS3	-0.029	0.12	-10000	0	-0.43	30	30
STAT1 (dimer)	0.035	0.058	-10000	0	-0.34	5	5
JAK2	0.03	0.014	-10000	0	-10000	0	0
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.057	0.06	-10000	0	-0.21	7	7
EPO/EPOR	0.031	0.03	-10000	0	-0.34	1	1
LYN	0.022	0.036	-10000	0	-0.44	2	2
TEC/VAV2	0.047	0.071	0.26	7	-0.23	6	13
elevation of cytosolic calcium ion concentration	0.029	0.013	-10000	0	-10000	0	0
SHC1	0.024	0.014	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	0.045	0.037	-10000	0	-0.29	2	2
mol:IP3	0.028	0.049	-10000	0	-0.35	3	3
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.069	0.08	0.28	18	-0.33	3	21
SH2B3	0.03	0.016	-10000	0	-0.13	2	2
NFKB1	0.039	0.062	0.16	85	-0.26	2	87
EPO/EPOR (dimer)/JAK2/SOCS3	-0.003	0.05	-10000	0	-0.21	24	24
PTPN6	0.048	0.082	0.29	20	-0.39	1	21
TEC/VAV2/GRB2	0.055	0.072	0.27	7	-0.26	3	10
EPOR	0.029	0.013	-10000	0	-10000	0	0
INPP5D	0.022	0.037	-10000	0	-0.28	6	6
mol:GDP	0.07	0.073	0.26	21	-0.33	2	23
SOS1	0.026	0.002	-10000	0	-10000	0	0
PLCG2	0.018	0.055	-10000	0	-0.29	13	13
CRKL/CBL/C3G	0.059	0.065	0.27	7	-10000	0	7
VAV2	0.05	0.081	0.28	23	-0.38	1	24
CBL	0.05	0.079	0.28	21	-0.21	1	22
SHC/Grb2/SOS1	0.028	0.04	-10000	0	-0.36	1	1
STAT5A	0.025	0.074	-10000	0	-0.36	13	13
GRB2	0.025	0.006	-10000	0	-10000	0	0
STAT5 (dimer)	0.039	0.079	-10000	0	-0.39	9	9
LYN/PLCgamma2	0.029	0.051	-10000	0	-0.28	11	11
PTPN11	0.026	0.003	-10000	0	-10000	0	0
BTK	0.046	0.096	0.27	24	-0.28	14	38
BCL2	0.056	0.12	0.36	1	-0.74	9	10

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	-0.008	0.11	0.23	1	-0.47	17	18
BAG4	0.014	0.071	-10000	0	-0.43	13	13
BAD	0.005	0.058	0.24	14	-0.17	5	19
NFKBIA	0.026	0.004	-10000	0	-10000	0	0
BIRC3	-0.002	0.099	-10000	0	-0.3	42	42
BAX	0.007	0.05	0.18	17	-0.15	7	24
EnzymeConsortium:3.1.4.12	0	0.03	0.065	5	-0.096	20	25
IKBKB	-0.003	0.12	0.24	5	-0.44	17	22
MAP2K2	0.003	0.057	0.18	23	-0.2	1	24
MAP2K1	-0.001	0.051	0.18	9	-0.2	1	10
SMPD1	0.001	0.038	0.13	8	-0.13	10	18
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	-0.001	0.12	0.3	7	-0.48	14	21
MAP2K4	-0.001	0.048	0.17	9	-0.17	5	14
protein ubiquitination	-0.005	0.11	0.22	1	-0.47	16	17
EnzymeConsortium:2.7.1.37	-0.001	0.058	0.19	10	-0.2	2	12
response to UV	0	0.001	0.002	9	-0.002	3	12
RAF1	0	0.051	0.18	10	-0.19	2	12
CRADD	0.026	0.003	-10000	0	-10000	0	0
mol:ceramide	0.002	0.046	0.12	7	-0.14	19	26
I-kappa-B-alpha/RELA/p50/ubiquitin	0.034	0.008	-10000	0	-10000	0	0
MADD	0.025	0.005	-10000	0	-10000	0	0
MAP3K1	0.001	0.048	0.16	8	-0.15	14	22
TRADD	0.025	0.02	-10000	0	-0.43	1	1
RELA/p50	0.025	0.005	-10000	0	-10000	0	0
MAPK3	0.005	0.055	0.18	10	-0.2	2	12
MAPK1	0.004	0.056	0.18	10	-0.23	2	12
p50/RELA/I-kappa-B-alpha	0.037	0.009	-10000	0	-10000	0	0
FADD	-0.006	0.11	0.26	7	-0.48	15	22
KSR1	0	0.047	0.15	5	-0.18	4	9
MAPK8	-0.006	0.05	0.19	4	-0.19	10	14
TRAF2	0.025	0.005	-10000	0	-10000	0	0
response to radiation	0	0	0.002	2	-10000	0	2
CHUK	-0.007	0.11	0.23	2	-0.46	16	18
TNF R/SODD	0.023	0.063	-10000	0	-0.31	17	17
TNF	-0.06	0.16	-10000	0	-0.27	151	151
CYCS	0.016	0.061	0.19	27	-0.14	3	30
IKBKG	-0.007	0.11	0.22	1	-0.46	16	17
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.006	0.12	-10000	0	-0.44	22	22
RELA	0.025	0.005	-10000	0	-10000	0	0
RIPK1	0.026	0.003	-10000	0	-10000	0	0
AIFM1	0.008	0.052	0.16	26	-0.15	4	30
TNF/TNF R/SODD	0	0.12	-10000	0	-0.27	77	77
TNFRSF1A	0.017	0.054	-10000	0	-0.34	10	10
response to heat	0	0	0.002	2	-10000	0	2
CASP8	0.022	0.08	-10000	0	-0.85	3	3
NSMAF	-0.002	0.12	0.24	6	-0.45	17	23
response to hydrogen peroxide	0	0.001	0.002	9	-0.002	3	12
BCL2	0.021	0.045	-10000	0	-0.43	5	5

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.025	0.009	-10000	0	-0.13	1	1
NFATC1	0.002	0.11	0.25	4	-0.36	24	28
NFATC2	-0.011	0.082	0.14	2	-0.23	40	42
NFATC3	0.007	0.059	-10000	0	-0.34	14	14
YWHAE	0.026	0.002	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.044	0.15	0.17	3	-0.41	48	51
Exportin 1/Ran/NUP214	0.051	0.012	-10000	0	-10000	0	0
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.064	0.17	-10000	0	-0.37	73	73
BCL2/BAX	0.029	0.034	-10000	0	-0.28	5	5
CaM/Ca2+/Calcineurin A alpha-beta B1	0.018	0.008	-10000	0	-0.089	1	1
CaM/Ca2+	0.018	0.008	-10000	0	-0.089	1	1
BAX	0.021	0.01	-10000	0	-10000	0	0
MAPK14	0.026	0.003	-10000	0	-10000	0	0
BAD	0.025	0.005	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.03	0.15	-10000	0	-0.4	46	46
Calcineurin A alpha-beta B1/BCL2	0.021	0.045	-10000	0	-0.43	5	5
FKBP8	0.025	0.006	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.03	0.14	0.39	46	-10000	0	46
KPNB1	0.026	0.003	-10000	0	-10000	0	0
KPNA2	0.025	0.009	-10000	0	-10000	0	0
XPO1	0.026	0.002	-10000	0	-10000	0	0
SFN	-0.023	0.11	-10000	0	-0.22	90	90
MAP3K8	0.016	0.047	-10000	0	-0.2	17	17
NFAT4/CK1 alpha	0.016	0.042	-10000	0	-0.19	13	13
MEF2D/NFAT1/Cbp/p300	0.019	0.1	-10000	0	-0.28	25	25
CABIN1	-0.044	0.15	0.17	3	-0.42	48	51
CALM1	0.025	0.009	-10000	0	-0.14	1	1
RAN	0.026	0.003	-10000	0	-10000	0	0
MAP3K1	0.024	0.019	-10000	0	-10000	0	0
CAMK4	-0.094	0.19	-10000	0	-0.43	121	121
mol:Ca2+	0	0.002	-10000	0	-10000	0	0
MAPK3	0.026	0.002	-10000	0	-10000	0	0
YWHAH	0.019	0.033	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.024	0.043	-10000	0	-0.3	3	3
YWHAB	0.025	0.005	-10000	0	-10000	0	0
MAPK8	0.014	0.071	-10000	0	-0.43	13	13
MAPK9	0.026	0.004	-10000	0	-10000	0	0
YWHAG	0.019	0.024	-10000	0	-0.13	11	11
FKBP1A	0.025	0.005	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.001	0.13	0.26	1	-0.35	37	38
PRKCH	0.025	0.005	-10000	0	-10000	0	0
CABIN1/Cbp/p300	0.035	0.032	-10000	0	-0.3	4	4
CASP3	0.025	0.009	-10000	0	-0.13	1	1
PIM1	0.024	0.017	-10000	0	-0.13	6	6
Calcineurin A alpha-beta B1/FKBP12/FK506	0.017	0.004	-10000	0	-10000	0	0
apoptosis	0.015	0.019	-10000	0	-0.31	1	1
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.004	0.046	-10000	0	-0.22	2	2
PRKCB	-0.007	0.098	-10000	0	-0.22	68	68
PRKCE	0.022	0.034	-10000	0	-0.2	9	9
JNK2/NFAT4	-0.001	0.078	-10000	0	-0.31	14	14
BAD/BCL-XL	0.036	0.01	-10000	0	-10000	0	0
PRKCD	0.003	0.1	-10000	0	-0.43	26	26
NUP214	0.025	0.005	-10000	0	-10000	0	0
PRKCZ	0.007	0.076	-10000	0	-0.43	14	14
PRKCA	0.024	0.021	-10000	0	-0.43	1	1
PRKCG	-0.066	0.15	-10000	0	-0.26	159	159
PRKCQ	0.015	0.061	-10000	0	-0.43	9	9
FKBP38/BCL2	0.033	0.034	-10000	0	-0.3	5	5
EP300	0.022	0.04	-10000	0	-0.43	4	4
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.025	0.005	-10000	0	-10000	0	0
NFATc/JNK1	0.008	0.11	0.26	1	-0.35	25	26
CaM/Ca2+/FKBP38	0.032	0.012	-10000	0	-10000	0	0
FKBP12/FK506	0.019	0.004	-10000	0	-10000	0	0
CSNK1A1	0.012	0.009	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.044	0.12	-10000	0	-0.25	122	122
NFATc/ERK1	0.015	0.11	0.26	3	-0.35	23	26
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.067	0.17	-10000	0	-0.37	78	78
NR4A1	-0.001	0.099	0.22	3	-0.38	15	18
GSK3B	0.025	0.02	-10000	0	-0.43	1	1
positive T cell selection	0.007	0.059	-10000	0	-0.34	14	14
NFAT1/CK1 alpha	-0.003	0.06	-10000	0	-0.19	22	22
RCH1/ KPNB1	0.037	0.009	-10000	0	-10000	0	0
YWHAQ	0.026	0.003	-10000	0	-10000	0	0
PRKACA	0.025	0.005	-10000	0	-10000	0	0
AKAP5	0.009	0.058	-10000	0	-0.16	45	45
MEF2D	0.024	0.012	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.023	0.008	-10000	0	-10000	0	0
NFATc/p38 alpha	0.014	0.11	0.26	3	-0.35	24	27
CREBBP	0.026	0.006	-10000	0	-10000	0	0
BCL2	0.021	0.045	-10000	0	-0.43	5	5

×

IL2 signaling events mediated by STAT5

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
GAB2	0.026	0.005	-10000	0	-10000	0	0
ELF1	0.013	0.052	-10000	0	-0.33	8	8
CCNA2	-0.007	0.099	-10000	0	-0.24	63	63
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
JAK3	-0.009	0.1	-10000	0	-0.25	65	65
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
JAK1	0.022	0.01	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.017	0.13	-10000	0	-0.42	21	21
SHC1	0.025	0.015	-10000	0	-10000	0	0
SP1	0.027	0.034	-10000	0	-0.33	4	4
IL2RA	-0.015	0.093	-10000	0	-0.7	8	8
IL2RB	-0.028	0.13	-10000	0	-0.43	39	39
SOS1	0.027	0.002	-10000	0	-10000	0	0
IL2RG	0.001	0.087	-10000	0	-0.22	52	52
G1/S transition of mitotic cell cycle	0.004	0.17	0.28	5	-0.48	40	45
PTPN11	0.026	0.004	-10000	0	-10000	0	0
CCND2	0.013	0.066	-10000	0	-0.7	4	4
LCK	-0.019	0.11	-10000	0	-0.43	30	30
GRB2	0.025	0.006	-10000	0	-10000	0	0
IL2	0.016	0.004	-10000	0	-10000	0	0
CDK6	0.004	0.083	-10000	0	-0.43	17	17
CCND3	-0.012	0.12	-10000	0	-0.47	6	6

×

LPA4-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
ADCY4	-0.009	0.027	-10000	0	-0.26	5	5
ADCY5	-0.014	0.046	-10000	0	-0.27	15	15
ADCY6	-0.007	0.017	-10000	0	-0.26	2	2
ADCY7	-0.007	0.017	-10000	0	-0.26	2	2
ADCY1	-0.03	0.069	-10000	0	-0.24	46	46
ADCY2	-0.012	0.04	-10000	0	-0.26	13	13
ADCY3	-0.007	0.017	-10000	0	-0.26	2	2
ADCY8	-0.031	0.075	-10000	0	-0.26	51	51
PRKCE	0.005	0.022	-10000	0	-0.3	2	2
ADCY9	-0.008	0.023	-10000	0	-0.26	4	4
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	0.001	0.076	0.18	22	-0.22	17	39

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.026	0.008	-10000	0	-0.13	1	1
Rac1/GDP	0.022	0.014	-10000	0	-10000	0	0
DOCK1	0.022	0.035	-10000	0	-0.43	3	3
ITGA4	-0.008	0.1	-10000	0	-0.26	61	61
RAC1	0.023	0.009	-10000	0	-10000	0	0
alpha4/beta7 Integrin	-0.005	0.1	-10000	0	-0.28	56	56
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.026	0.002	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.033	0.067	-10000	0	-0.25	25	25
alpha4/beta7 Integrin/Paxillin	0.009	0.083	0.18	3	-0.24	42	45
lamellipodium assembly	0.023	0.049	0.27	1	-0.43	3	4
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
PI3K	0.038	0.007	-10000	0	-10000	0	0
ARF6	0.026	0.004	-10000	0	-10000	0	0
TLN1	0.026	0.005	-10000	0	-10000	0	0
PXN	0.013	0.003	-10000	0	-10000	0	0
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
ARF6/GTP	0.037	0.057	-10000	0	-0.21	22	22
cell adhesion	0.037	0.06	-10000	0	-0.22	22	22
CRKL/CBL	0.036	0.012	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.02	0.062	0.17	1	-0.24	22	23
ITGB1	0.023	0.012	-10000	0	-10000	0	0
ITGB7	0.001	0.091	-10000	0	-0.26	44	44
ARF6/GDP	0.024	0.013	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0	0.097	-10000	0	-0.23	67	67
p130Cas/Crk/Dock1	0.047	0.031	-10000	0	-0.26	4	4
VCAM1	-0.033	0.13	-10000	0	-0.3	85	85
alpha4/beta1 Integrin/Paxillin/Talin	0.038	0.061	-10000	0	-0.22	22	22
alpha4/beta1 Integrin/Paxillin/GIT1	0.039	0.061	-10000	0	-0.22	22	22
BCAR1	0.025	0.02	-10000	0	-0.43	1	1
mol:GDP	-0.038	0.06	0.22	22	-10000	0	22
CBL	0.025	0.007	-10000	0	-10000	0	0
PRKACA	0.025	0.005	-10000	0	-10000	0	0
GIT1	0.026	0.002	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.038	0.061	-10000	0	-0.22	22	22
Rac1/GTP	0.023	0.054	0.28	1	-0.48	3	4

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	0.029	0.039	-10000	0	-0.25	5	5
alphaV beta3 Integrin	0.044	0.053	-10000	0	-0.26	14	14
PTK2	0.01	0.11	0.34	7	-0.37	16	23
IGF1R	0.026	0.004	-10000	0	-10000	0	0
PI4KB	0.026	0.004	-10000	0	-10000	0	0
MFGE8	0.023	0.035	-10000	0	-0.35	4	4
SRC	0.025	0.005	-10000	0	-10000	0	0
CDKN1B	0.005	0.08	-10000	0	-0.41	17	17
VEGFA	0.019	0.032	-10000	0	-0.13	22	22
ILK	0.005	0.078	-10000	0	-0.38	18	18
ROCK1	0.026	0.004	-10000	0	-10000	0	0
AKT1	-0.002	0.072	0.18	1	-0.37	17	18
PTK2B	0	0.061	0.18	21	-0.22	14	35
alphaV/beta3 Integrin/JAM-A	0.04	0.069	0.2	1	-0.23	27	28
CBL	0.025	0.007	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.029	0.054	-10000	0	-0.26	12	12
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.057	0.048	-10000	0	-0.23	12	12
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.011	0.056	-10000	0	-0.28	6	6
alphaV/beta3 Integrin/Syndecan-1	0.035	0.071	-10000	0	-0.21	38	38
PI4KA	0.023	0.021	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.038	0.068	-10000	0	-0.21	26	26
PI4 Kinase	0.035	0.018	-10000	0	-10000	0	0
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
alphaV/beta3 Integrin/Osteopontin	0.014	0.099	-10000	0	-0.22	74	74
RPS6KB1	-0.021	0.062	0.38	3	-0.25	2	5
TLN1	0.026	0.005	-10000	0	-10000	0	0
MAPK3	-0.002	0.085	-10000	0	-0.39	16	16
GPR124	0.024	0.015	-10000	0	-0.13	4	4
MAPK1	-0.001	0.084	-10000	0	-0.39	16	16
PXN	0.026	0.004	-10000	0	-10000	0	0
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	0.031	0.086	-10000	0	-0.25	41	41
cell adhesion	0.028	0.056	-10000	0	-0.25	15	15
ANGPTL3	0.002	0.02	-10000	0	-0.13	1	1
VEGFR2 homodimer/VEGFA homodimer/Src	0.047	0.028	-10000	0	-0.2	4	4
IGF-1R heterotetramer	0.026	0.004	-10000	0	-10000	0	0
Rac1/GDP	0.017	0.007	-10000	0	-10000	0	0
TGFBR2	0.024	0.016	-10000	0	-0.13	5	5
ITGB3	-0.001	0.082	-10000	0	-0.19	64	64
IGF1	0.012	0.076	-10000	0	-0.34	20	20
RAC1	0.023	0.009	-10000	0	-10000	0	0
regulation of cell-matrix adhesion	0.03	0.059	-10000	0	-0.24	14	14
apoptosis	0.026	0.002	-10000	0	-10000	0	0
CD47	0.026	0.003	-10000	0	-10000	0	0
alphaV/beta3 Integrin/CD47	0.047	0.048	-10000	0	-0.26	12	12
VCL	0.022	0.032	-10000	0	-0.23	6	6
alphaV/beta3 Integrin/Del1	0.015	0.11	-10000	0	-0.28	59	59
CSF1	0.017	0.045	-10000	0	-0.43	5	5
PIK3C2A	0.003	0.084	-10000	0	-0.41	19	19
PI4 Kinase/Pyk2	0.006	0.069	-10000	0	-0.21	29	29
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.05	0.061	-10000	0	-0.23	15	15
FAK1/Vinculin	0.019	0.095	0.26	14	-0.32	14	28
alphaV beta3/Integrin/ppsTEM5	0.044	0.05	-10000	0	-0.24	14	14
RHOA	0.026	0.004	-10000	0	-10000	0	0
VTN	0.012	0.075	-10000	0	-0.35	19	19
BCAR1	0.025	0.02	-10000	0	-0.43	1	1
FGF2	0.024	0.029	-10000	0	-0.43	2	2
F11R	0.01	0.024	-10000	0	-0.3	2	2
alphaV/beta3 Integrin/Lactadherin	0.045	0.054	-10000	0	-0.26	15	15
alphaV/beta3 Integrin/TGFBR2	0.045	0.051	-10000	0	-0.23	15	15
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.047	0.042	-10000	0	-0.24	5	5
HSP90AA1	0.025	0.005	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	0.044	0.045	-10000	0	-0.23	12	12
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.021	0.029	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Pyk2	0.032	0.064	0.18	16	-0.22	15	31
SDC1	0.007	0.07	-10000	0	-0.19	43	43
VAV3	-0.008	0.074	0.18	26	-0.23	31	57
PTPN11	0.026	0.003	-10000	0	-10000	0	0
IRS1	0.026	0.003	-10000	0	-10000	0	0
FAK1/Paxillin	0.02	0.095	0.27	16	-0.31	14	30
cell migration	0.014	0.088	0.24	17	-0.31	11	28
ITGAV	0.026	0.002	-10000	0	-10000	0	0
PI3K	0.05	0.067	-10000	0	-0.21	25	25
SPP1	-0.024	0.12	-10000	0	-0.26	87	87
KDR	0.021	0.039	-10000	0	-0.23	9	9
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.026	0.002	-10000	0	-10000	0	0
COL4A3	-0.011	0.1	-10000	0	-0.22	78	78
angiogenesis	0	0.097	-10000	0	-0.42	16	16
Rac1/GTP	0.003	0.068	-10000	0	-0.21	29	29
EDIL3	-0.024	0.14	-10000	0	-0.43	53	53
cell proliferation	0.03	0.06	-10000	0	-0.23	15	15

×

Wnt signaling

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
Noncanonical Wnts/FZD	-0.007	0.087	-9999	-0.27	44	44
FZD6	0.015	0.04	-9999	-0.43	1	1
WNT6	0.003	0.087	-9999	-0.43	17	17
WNT4	0.008	0.057	-9999	-0.43	5	5
FZD3	0.023	0.035	-9999	-0.43	3	3
WNT5A	0.01	0.078	-9999	-0.33	22	22
WNT11	0.009	0.075	-9999	-0.43	13	13

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.036	0.064	-10000	0	-0.22	25	25
ER alpha/Gai/GDP/Gbeta gamma	-0.023	0.12	-10000	0	-0.42	14	14
AKT1	-0.009	0.17	-10000	0	-0.67	30	30
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.005	0.18	-10000	0	-0.69	30	30
mol:Ca2+	-0.018	0.093	-10000	0	-0.38	23	23
IGF1R	0.026	0.004	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	0.011	0.076	-10000	0	-0.26	34	34
SHC1	0.024	0.014	-10000	0	-10000	0	0
apoptosis	0.008	0.16	0.64	30	-10000	0	30
RhoA/GTP	0.012	0.033	-10000	0	-0.2	9	9
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	0	0.12	-10000	0	-0.4	14	14
regulation of stress fiber formation	0.003	0.066	0.39	2	-0.17	16	18
E2/ERA-ERB (dimer)	0.018	0.06	-10000	0	-0.24	23	23
KRAS	0.025	0.005	-10000	0	-10000	0	0
G13/GTP	0.024	0.041	-10000	0	-0.23	11	11
pseudopodium formation	-0.003	0.066	0.17	16	-0.39	2	18
E2/ER alpha (dimer)/PELP1	0.025	0.045	-10000	0	-0.26	11	11
GRB2	0.025	0.006	-10000	0	-10000	0	0
GNG2	0.022	0.04	-10000	0	-0.43	4	4
GNAO1	0.022	0.045	-10000	0	-0.43	5	5
HRAS	0.025	0.006	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.004	0.13	0.28	2	-0.41	23	25
E2/ER beta (dimer)	0.012	0.045	-10000	0	-0.3	10	10
mol:GDP	0	0.068	-10000	0	-0.28	22	22
mol:NADP	0.004	0.13	0.28	2	-0.41	23	25
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
mol:IP3	-0.019	0.097	-10000	0	-0.4	23	23
IGF-1R heterotetramer	0.026	0.004	-10000	0	-10000	0	0
PLCB1	-0.01	0.09	-10000	0	-0.38	20	20
PLCB2	-0.01	0.096	-10000	0	-0.4	22	22
IGF1	0.012	0.076	-10000	0	-0.34	20	20
mol:L-citrulline	0.004	0.13	0.28	2	-0.41	23	25
RHOA	0.026	0.004	-10000	0	-10000	0	0
Gai/GDP	0.008	0.11	-10000	0	-0.6	15	15
JNK cascade	0.011	0.045	-10000	0	-0.3	10	10
BCAR1	0.025	0.02	-10000	0	-0.43	1	1
ESR2	0.015	0.065	-10000	0	-0.33	15	15
GNAQ	0.026	0.004	-10000	0	-10000	0	0
ESR1	0.011	0.07	-10000	0	-0.26	25	25
Gq family/GDP/Gbeta gamma	-0.024	0.17	-10000	0	-0.6	27	27
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.029	0.071	-10000	0	-1.2	1	1
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	0.001	0.11	-10000	0	-0.4	13	13
GNAZ	0.026	0.004	-10000	0	-10000	0	0
E2/ER alpha (dimer)	0.009	0.049	-10000	0	-0.3	11	11
STRN	0.005	0.096	-10000	0	-0.42	25	25
GNAL	-0.028	0.15	-10000	0	-0.42	61	61
PELP1	0.026	0.002	-10000	0	-10000	0	0
MAPK11	0.003	0.05	-10000	0	-0.26	18	18
GNAI2	0.025	0.005	-10000	0	-10000	0	0
GNAI3	0.021	0.01	-10000	0	-10000	0	0
GNAI1	0.019	0.036	-10000	0	-0.43	3	3
HBEGF	-0.019	0.14	0.35	21	-0.38	16	37
cAMP biosynthetic process	-0.011	0.089	-10000	0	-0.21	78	78
SRC	-0.025	0.12	-10000	0	-0.37	19	19
PI3K	0.038	0.007	-10000	0	-10000	0	0
GNB1	0.022	0.01	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	0.022	0.072	-10000	0	-0.27	19	19
SOS1	0.026	0.002	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.023	0.09	-10000	0	-0.31	21	21
Gs family/GTP	-0.005	0.093	-10000	0	-0.22	78	78
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.037	0.022	-10000	0	-10000	0	0
vasodilation	0.005	0.12	0.28	2	-0.38	24	26
mol:DAG	-0.019	0.097	-10000	0	-0.4	23	23
Gs family/GDP/Gbeta gamma	-0.014	0.088	-10000	0	-0.29	24	24
MSN	-0.003	0.069	0.18	16	-0.42	2	18
Gq family/GTP	0.001	0.089	-10000	0	-0.39	19	19
mol:PI-3-4-5-P3	-0.004	0.17	-10000	0	-0.66	30	30
NRAS	0.021	0.01	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.005	0.12	0.38	24	-0.28	2	26
GRB2/SOS1	0.037	0.009	-10000	0	-10000	0	0
RhoA/GDP	0.015	0.073	-10000	0	-0.28	20	20
NOS3	0.003	0.14	0.34	1	-0.43	23	24
GNA11	0.017	0.06	-10000	0	-0.43	9	9
MAPKKK cascade	-0.006	0.15	0.37	3	-0.46	32	35
E2/ER alpha (dimer)/PELP1/Src	0.003	0.12	0.26	9	-0.41	14	23
ruffle organization	-0.003	0.066	0.17	16	-0.39	2	18
ROCK2	0.002	0.07	0.32	1	-0.28	2	3
GNA14	0.009	0.081	-10000	0	-0.34	23	23
GNA15	0.013	0.07	-10000	0	-0.43	12	12
GNA13	0.025	0.005	-10000	0	-10000	0	0
MMP9	-0.039	0.13	0.33	4	-0.37	24	28
MMP2	-0.014	0.13	0.28	12	-0.44	9	21

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
GNAO1	0.022	0.045	-10000	0	-0.43	5	5
CDC42/GTP	0.026	0.051	-10000	0	-0.23	8	8
PLCG1	0.005	0.054	-10000	0	-0.24	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.025	0.005	-10000	0	-10000	0	0
GNAI3	0.021	0.01	-10000	0	-10000	0	0
G12/G13	0.032	0.015	-10000	0	-10000	0	0
cell migration	0.025	0.05	-10000	0	-0.23	8	8
S1PR5	-0.053	0.16	-10000	0	-0.3	124	124
S1PR4	0.019	0.042	-10000	0	-0.43	3	3
MAPK3	0.006	0.055	-10000	0	-0.24	8	8
MAPK1	0.007	0.05	-10000	0	-0.21	7	7
S1P/S1P5/Gi	-0.019	0.1	-10000	0	-0.24	67	67
GNAI1	0.019	0.036	-10000	0	-0.43	3	3
CDC42/GDP	0.016	0.007	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.016	0.094	-10000	0	-0.26	61	61
RHOA	0.045	0.087	0.22	81	-0.22	3	84
S1P/S1P4/Gi	0.011	0.058	-10000	0	-0.26	8	8
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	0.026	0.004	-10000	0	-10000	0	0
S1P/S1P4/G12/G13	0.04	0.029	-10000	0	-0.23	3	3
GNA12	0.022	0.009	-10000	0	-10000	0	0
GNA13	0.025	0.005	-10000	0	-10000	0	0
CDC42	0.022	0.01	-10000	0	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.014	0.071	-10000	0	-0.43	13	13
Caspase 8 (4 units)	0.031	0.06	-10000	0	-0.3	4	4
NEF	-0.001	0.011	-10000	0	-10000	0	0
NFKBIA	0.02	0.029	-10000	0	-0.14	1	1
BIRC3	-0.005	0.1	-10000	0	-0.45	24	24
CYCS	0.007	0.048	0.18	9	-0.33	2	11
RIPK1	0.026	0.003	-10000	0	-10000	0	0
CD247	0.01	0.068	-10000	0	-0.25	25	25
MAP2K7	0.025	0.086	-10000	0	-0.61	4	4
protein ubiquitination	0.018	0.089	0.25	7	-0.36	7	14
CRADD	0.026	0.003	-10000	0	-10000	0	0
DAXX	0.026	0.003	-10000	0	-10000	0	0
FAS	0.014	0.063	-10000	0	-0.28	18	18
BID	0.01	0.048	0.18	6	-0.22	11	17
NF-kappa-B/RelA/I kappa B alpha	0.038	0.069	-10000	0	-0.24	24	24
TRADD	0.025	0.02	-10000	0	-0.43	1	1
MAP3K5	0.02	0.049	-10000	0	-0.43	6	6
CFLAR	0.026	0.007	-10000	0	-10000	0	0
FADD	0.025	0.005	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.038	0.069	-10000	0	-0.25	24	24
MAPK8	0.019	0.083	-10000	0	-0.55	4	4
APAF1	0.026	0.003	-10000	0	-10000	0	0
TRAF1	0.019	0.053	-10000	0	-0.43	7	7
TRAF2	0.026	0.005	-10000	0	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.013	0.047	-10000	0	-0.23	12	12
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	-0.003	0.088	-10000	0	-0.42	10	10
CHUK	0.017	0.094	0.25	7	-0.37	8	15
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.061	0.054	-10000	0	-0.22	13	13
TCRz/NEF	0.009	0.052	-10000	0	-0.19	25	25
TNF	-0.06	0.16	-10000	0	-0.26	151	151
FASLG	-0.006	0.051	-10000	0	-0.26	8	8
NFKB1	0.021	0.027	-10000	0	-10000	0	0
TNFR1A/BAG4/TNF-alpha	0	0.12	-10000	0	-0.27	77	77
CASP6	0.027	0.099	-10000	0	-0.59	7	7
CASP7	0.007	0.13	0.29	14	-0.47	26	40
RELA	0.019	0.03	-10000	0	-10000	0	0
CASP2	0.02	0.011	-10000	0	-10000	0	0
CASP3	0.007	0.13	0.29	14	-0.47	27	41
TNFRSF1A	0.017	0.054	-10000	0	-0.34	10	10
TNFR1A/BAG4	0.023	0.063	-10000	0	-0.31	17	17
CASP8	0.021	0.033	-10000	0	-0.43	1	1
CASP9	0.022	0.012	-10000	0	-0.13	1	1
MAP3K14	0.014	0.094	-10000	0	-0.4	9	9
APAF-1/Caspase 9	0.004	0.083	-10000	0	-0.32	22	22
BCL2	0.015	0.083	0.27	1	-0.51	4	5

×

Signaling events mediated by PRL

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
CCNE1	0.021	0.014	-10000	0	-0.13	2	2
mol:Halofuginone	0.003	0.009	-10000	0	-0.2	1	1
ITGA1	0.015	0.059	-10000	0	-0.22	23	23
CDKN1A	-0.059	0.16	-10000	0	-0.37	95	95
PRL-3/alpha Tubulin	0.033	0.016	-10000	0	-10000	0	0
mol:Ca2+	-0.029	0.06	-10000	0	-0.32	21	21
AGT	0.006	0.092	-10000	0	-0.4	24	24
CCNA2	-0.038	0.079	-10000	0	-0.31	7	7
TUBA1B	0.026	0.004	-10000	0	-10000	0	0
EGR1	-0.027	0.095	-10000	0	-0.3	53	53
CDK2/Cyclin E1	-0.029	0.15	-10000	0	-0.37	56	56
MAPK3	0.012	0.008	-10000	0	-10000	0	0
PRL-2 /Rab GGTase beta	0.032	0.015	-10000	0	-10000	0	0
MAPK1	0.012	0.008	-10000	0	-10000	0	0
PTP4A1	-0.025	0.074	-10000	0	-0.62	1	1
PTP4A3	0.023	0.013	-10000	0	-0.13	2	2
PTP4A2	0.022	0.01	-10000	0	-10000	0	0
ITGB1	0.01	0.01	-10000	0	-10000	0	0
SRC	0.025	0.005	-10000	0	-10000	0	0
RAC1	0.006	0.036	-10000	0	-0.31	2	2
Rab GGTase beta/Rab GGTase alpha	0.032	0.016	-10000	0	-10000	0	0
PRL-1/ATF-5	-0.008	0.079	-10000	0	-0.57	1	1
RABGGTA	0.026	0.004	-10000	0	-10000	0	0
BCAR1	-0.017	0.019	0.24	1	-0.32	1	2
RHOC	-0.057	0.15	-10000	0	-0.36	95	95
RHOA	0.002	0.055	-10000	0	-0.32	10	10
cell motility	-0.014	0.095	0.28	1	-0.28	33	34
PRL-1/alpha Tubulin	-0.004	0.084	-10000	0	-0.58	1	1
PRL-3/alpha1 Integrin	0.027	0.042	-10000	0	-0.28	6	6
ROCK1	-0.017	0.093	0.28	1	-0.28	34	35
RABGGTB	0.022	0.01	-10000	0	-10000	0	0
CDK2	0.02	0.044	-10000	0	-0.43	4	4
mitosis	-0.025	0.073	-10000	0	-0.61	1	1
ATF5	0.02	0.018	-10000	0	-0.13	5	5

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.011	0.005	-10000	0	-10000	0	0
SMARCC1	0.014	0.032	-10000	0	-0.69	1	1
REL	0.007	0.086	-10000	0	-0.32	28	28
HDAC7	-0.017	0.079	-10000	0	-0.29	16	16
JUN	0.019	0.023	-10000	0	-0.13	9	9
EP300	0.022	0.04	-10000	0	-0.43	4	4
KAT2B	0.025	0.008	-10000	0	-10000	0	0
KAT5	0.025	0.005	-10000	0	-10000	0	0
MAPK14	0.007	0.02	-10000	0	-0.3	1	1
FOXO1	0.024	0.022	-10000	0	-0.28	2	2
T-DHT/AR	0.002	0.092	-10000	0	-0.3	17	17
MAP2K6	0.021	0.024	-10000	0	-0.43	1	1
BRM/BAF57	0.036	0.01	-10000	0	-10000	0	0
MAP2K4	0.022	0.018	-10000	0	-0.15	1	1
SMARCA2	0.025	0.006	-10000	0	-10000	0	0
PDE9A	0.008	0.092	-10000	0	-0.92	3	3
NCOA2	-0.005	0.11	-10000	0	-0.43	34	34
CEBPA	0.015	0.049	-10000	0	-0.43	5	5
EHMT2	0.026	0.003	-10000	0	-10000	0	0
cell proliferation	0.001	0.11	0.36	9	-0.42	8	17
NR0B1	-0.041	0.15	-10000	0	-0.31	102	102
EGR1	-0.038	0.14	-10000	0	-0.27	111	111
RXRs/9cRA	0.019	0.085	-10000	0	-0.23	52	52
AR/RACK1/Src	0.001	0.074	0.22	1	-0.26	10	11
AR/GR	-0.012	0.1	0.23	2	-0.24	69	71
GNB2L1	0.026	0.004	-10000	0	-10000	0	0
PKN1	0.025	0.005	-10000	0	-10000	0	0
RCHY1	0.026	0.004	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0.001	-10000	0	-10000	0	0
MAPK8	0	0.052	-10000	0	-0.31	13	13
T-DHT/AR/TIF2/CARM1	-0.002	0.1	0.35	1	-0.37	20	21
SRC	-0.013	0.044	0.2	8	-0.22	12	20
NR3C1	0.026	0.004	-10000	0	-10000	0	0
KLK3	-0.042	0.1	-10000	0	-0.45	3	3
APPBP2	0.022	0.014	-10000	0	-10000	0	0
TRIM24	0.02	0.011	-10000	0	-10000	0	0
T-DHT/AR/TIP60	-0.003	0.073	0.21	8	-0.3	10	18
TMPRSS2	-0.066	0.29	-10000	0	-0.99	45	45
RXRG	-0.027	0.14	-10000	0	-0.4	63	63
mol:9cRA	0	0	-10000	0	-10000	0	0
RXRA	0.025	0.005	-10000	0	-10000	0	0
RXRB	0.026	0.003	-10000	0	-10000	0	0
CARM1	0.025	0.006	-10000	0	-10000	0	0
NR2C2	0.018	0.06	-10000	0	-0.43	9	9
KLK2	-0.02	0.1	0.44	1	-0.39	14	15
AR	-0.029	0.099	0.13	3	-0.26	73	76
SENP1	0.026	0.004	-10000	0	-10000	0	0
HSP90AA1	0.025	0.005	-10000	0	-10000	0	0
MDM2	0.026	0.004	-10000	0	-10000	0	0
SRY	0	0.001	-10000	0	-10000	0	0
GATA2	0.015	0.065	-10000	0	-0.43	10	10
MYST2	0	0	-10000	0	-10000	0	0
HOXB13	-0.009	0.048	-10000	0	-0.13	57	57
T-DHT/AR/RACK1/Src	0.003	0.079	0.27	5	-0.27	10	15
positive regulation of transcription	0.015	0.064	-10000	0	-0.43	10	10
DNAJA1	0.022	0.015	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.016	0.008	-10000	0	-10000	0	0
NCOA1	0.03	0.011	-10000	0	-10000	0	0
SPDEF	-0.005	0.1	-10000	0	-0.28	51	51
T-DHT/AR/TIF2	-0.003	0.1	0.23	3	-0.37	21	24
T-DHT/AR/Hsp90	-0.004	0.072	0.22	6	-0.3	11	17
GSK3B	0.025	0.02	-10000	0	-0.43	1	1
NR2C1	0.026	0.003	-10000	0	-10000	0	0
mol:T-DHT	-0.017	0.04	-10000	0	-0.24	13	13
SIRT1	0.025	0.005	-10000	0	-10000	0	0
ZMIZ2	0.023	0.009	-10000	0	-10000	0	0
POU2F1	0.021	0.042	-10000	0	-0.43	1	1
T-DHT/AR/DAX-1	-0.032	0.1	0.22	7	-0.25	55	62
CREBBP	0.026	0.003	-10000	0	-10000	0	0
SMARCE1	0.026	0.003	-10000	0	-10000	0	0

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.02	0.076	-10000	0	-0.3	26	26
ATM	0.025	0.005	-10000	0	-10000	0	0
UBE2D3	0.026	0.004	-10000	0	-10000	0	0
PRKDC	0.025	0.005	-10000	0	-10000	0	0
ATR	0.026	0.003	-10000	0	-10000	0	0
UBE2L3	0.026	0.004	-10000	0	-10000	0	0
FANCD2	0.016	0.029	-10000	0	-0.29	4	4
protein ubiquitination	0.04	0.07	-10000	0	-0.22	27	27
XRCC5	0.026	0.003	-10000	0	-10000	0	0
XRCC6	0.026	0.004	-10000	0	-10000	0	0
M/R/N Complex	0.046	0.018	-10000	0	-10000	0	0
MRE11A	0.025	0.006	-10000	0	-10000	0	0
DNA-PK	0.05	0.014	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.024	0.062	-10000	0	-0.48	4	4
FANCF	0.025	0.005	-10000	0	-10000	0	0
BRCA1	0.025	0.012	-10000	0	-0.13	3	3
CCNE1	0.021	0.014	-10000	0	-0.13	2	2
CDK2/Cyclin E1	0.027	0.037	-10000	0	-0.28	5	5
FANCG	0.025	0.005	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.02	0.076	-10000	0	-0.3	27	27
FANCE	0.026	0.003	-10000	0	-10000	0	0
FANCC	0.024	0.022	-10000	0	-0.43	1	1
NBN	0.024	0.007	-10000	0	-10000	0	0
FANCA	0.009	0.069	-10000	0	-0.2	38	38
DNA repair	0.01	0.09	0.27	9	-0.4	7	16
BRCA1/BARD1/ubiquitin	0.02	0.076	-10000	0	-0.3	27	27
BARD1/DNA-PK	0.049	0.065	-10000	0	-0.24	24	24
FANCL	0.026	0.002	-10000	0	-10000	0	0
mRNA polyadenylation	-0.019	0.075	0.3	26	-10000	0	26
BRCA1/BARD1/CTIP/M/R/N Complex	0.017	0.058	-10000	0	-0.38	2	2
BRCA1/BACH1/BARD1/TopBP1	0.035	0.072	-10000	0	-0.26	27	27
BRCA1/BARD1/P53	0.043	0.083	-10000	0	-0.25	37	37
BARD1/CSTF1/BRCA1	0.035	0.069	-10000	0	-0.26	26	26
BRCA1/BACH1	0.025	0.012	-10000	0	-0.13	3	3
BARD1	0.002	0.1	-10000	0	-0.41	28	28
PCNA	0.025	0.011	-10000	0	-0.13	2	2
BRCA1/BARD1/UbcH5C	0.035	0.069	-10000	0	-0.25	27	27
BRCA1/BARD1/UbcH7	0.036	0.068	-10000	0	-0.25	26	26
BRCA1/BARD1/RAD51/PCNA	0.04	0.085	-10000	0	-0.24	39	39
BARD1/DNA-PK/P53	0.051	0.08	-10000	0	-0.23	34	34
BRCA1/BARD1/Ubiquitin	0.02	0.076	-10000	0	-0.3	27	27
BRCA1/BARD1/CTIP	0.028	0.06	0.21	1	-0.24	24	25
FA complex	0.024	0.037	-10000	0	-10000	0	0
BARD1/EWS	0.021	0.074	-10000	0	-0.3	25	25
RBBP8	0.013	0.005	-10000	0	-10000	0	0
TP53	0.014	0.072	-10000	0	-0.41	14	14
TOPBP1	0.025	0.02	-10000	0	-0.43	1	1
G1/S transition of mitotic cell cycle	-0.041	0.082	0.24	37	-10000	0	37
BRCA1/BARD1	0.045	0.073	-10000	0	-0.22	27	27
CSTF1	0.025	0.005	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.003	0.071	-10000	0	-0.3	26	26
CDK2	0.02	0.044	-10000	0	-0.43	4	4
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.001	0.085	-10000	0	-0.2	61	61
RAD50	0.026	0.003	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.02	0.076	-10000	0	-0.3	27	27
EWSR1	0.026	0.004	-10000	0	-10000	0	0

×

Sphingosine 1-phosphate (S1P) pathway

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
SPHK2	0.021	0.01	-9999	-10000	0	0
SPHK1	0.004	0.086	-9999	-0.43	17	17
GNAI2	0.025	0.005	-9999	-10000	0	0
mol:S1P	0	0.064	-9999	-0.34	16	16
GNAO1	0.022	0.045	-9999	-0.43	5	5
mol:Sphinganine-1-P	0.003	0.041	-9999	-0.3	7	7
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.022	0.074	-9999	-0.28	16	16
GNAI3	0.021	0.01	-9999	-10000	0	0
G12/G13	0.032	0.015	-9999	-10000	0	0
S1PR3	0.005	0.075	-9999	-0.43	11	11
S1PR2	0.022	0.036	-9999	-0.43	3	3
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.014	0.062	-9999	-0.29	17	17
S1PR5	-0.053	0.16	-9999	-0.3	124	124
S1PR4	0.019	0.042	-9999	-0.43	3	3
GNAI1	0.019	0.036	-9999	-0.43	3	3
S1P/S1P5/G12	-0.016	0.11	-9999	-0.26	71	71
S1P/S1P3/Gq	-0.006	0.11	-9999	-0.38	29	29
S1P/S1P4/Gi	0.003	0.084	-9999	-0.28	17	17
GNAQ	0.026	0.004	-9999	-10000	0	0
GNAZ	0.026	0.004	-9999	-10000	0	0
GNA14	0.009	0.081	-9999	-0.34	23	23
GNA15	0.013	0.07	-9999	-0.43	12	12
GNA12	0.022	0.009	-9999	-10000	0	0
GNA13	0.025	0.005	-9999	-10000	0	0
GNA11	0.017	0.06	-9999	-0.43	9	9
ABCC1	0.025	0.014	-9999	-0.13	4	4

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.029	0.023	-10000	0	-0.3	2	2
VEGFR1 homodimer/NRP1	0.012	0.02	-10000	0	-0.3	2	2
mol:DAG	-0.014	0.074	-10000	0	-0.23	49	49
VEGFR1 homodimer/NRP1/VEGFR 121	0.024	0.027	-10000	0	-0.27	2	2
CaM/Ca2+	0	0.076	-10000	0	-0.22	49	49
HIF1A	0.03	0.021	-10000	0	-0.42	1	1
GAB1	0.025	0.02	-10000	0	-0.43	1	1
AKT1	-0.015	0.082	-10000	0	-0.49	1	1
PLCG1	-0.014	0.075	-10000	0	-0.23	49	49
NOS3	-0.009	0.07	-10000	0	-0.3	3	3
CBL	0.025	0.007	-10000	0	-10000	0	0
mol:NO	0.005	0.081	0.28	1	-0.29	3	4
FLT1	0.017	0.024	-10000	0	-0.35	2	2
PGF	-0.034	0.14	-10000	0	-0.31	90	90
VEGFR1 homodimer/NRP2/VEGFR121	0.042	0.035	-10000	0	-0.23	6	6
CALM1	0.025	0.009	-10000	0	-0.13	1	1
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
eNOS/Hsp90	0.021	0.089	0.28	3	-0.29	2	5
endothelial cell proliferation	-0.026	0.097	0.27	1	-0.32	15	16
mol:Ca2+	-0.014	0.074	-10000	0	-0.23	49	49
MAPK3	-0.027	0.061	0.18	2	-0.26	1	3
MAPK1	-0.027	0.061	0.17	3	-0.26	1	4
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
PLGF homodimer	-0.034	0.14	-10000	0	-0.31	90	90
PRKACA	0.025	0.005	-10000	0	-10000	0	0
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	0.006	0.051	-10000	0	-0.43	2	2
VEGFA homodimer	0.019	0.032	-10000	0	-0.13	22	22
VEGFR1 homodimer/VEGFA homodimer	0.027	0.03	-10000	0	-0.3	2	2
platelet activating factor biosynthetic process	-0.027	0.059	-10000	0	-0.26	1	1
PI3K	0.028	0.088	-10000	0	-0.22	55	55
PRKCA	-0.027	0.064	0.18	3	-0.27	1	4
PRKCB	-0.038	0.074	0.18	3	-0.28	11	14
VEGFR1 homodimer/PLGF homodimer	-0.007	0.091	-10000	0	-0.26	57	57
VEGFA	0.019	0.032	-10000	0	-0.13	22	22
VEGFB	0.025	0.005	-10000	0	-10000	0	0
mol:IP3	-0.014	0.074	-10000	0	-0.23	49	49
RASA1	0.014	0.021	-10000	0	-0.32	1	1
NRP2	0.021	0.046	-10000	0	-0.32	8	8
VEGFR1 homodimer	0.017	0.024	-10000	0	-0.35	2	2
VEGFB homodimer	0.025	0.005	-10000	0	-10000	0	0
NCK1	0.025	0.02	-10000	0	-0.43	1	1
eNOS/Caveolin-1	0.002	0.076	-10000	0	-0.3	1	1
PTPN11	0.026	0.003	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.026	0.087	-10000	0	-0.22	55	55
mol:L-citrulline	0.005	0.081	0.28	1	-0.29	3	4
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.055	0.031	-10000	0	-0.26	2	2
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.044	0.021	-10000	0	-0.23	1	1
CD2AP	0.026	0.002	-10000	0	-10000	0	0
PI3K/GAB1	0.036	0.089	-10000	0	-0.23	1	1
PDPK1	-0.012	0.075	-10000	0	-0.43	1	1
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.044	0.025	-10000	0	-0.27	2	2
mol:NADP	0.005	0.081	0.28	1	-0.29	3	4
HSP90AA1	0.025	0.005	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.053	0.03	-10000	0	-0.26	2	2
VEGFR1 homodimer/NRP2	0.027	0.034	-10000	0	-0.25	6	6

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.012	0.07	-10000	0	-0.26	25	25
positive regulation of NF-kappaB transcription factor activity	0.022	0.06	-10000	0	-0.3	13	13
MAP2K4	0.016	0.048	0.21	1	-0.24	1	2
IKBKB	0.025	0.005	-10000	0	-10000	0	0
TNFRSF10B	0.022	0.036	-10000	0	-0.35	4	4
TNFRSF10A	0	0.098	-10000	0	-0.43	24	24
SMPD1	0.007	0.031	-10000	0	-0.18	13	13
IKBKG	0.026	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.019	0.038	-10000	0	-0.17	15	15
TRAIL/TRAILR2	0.024	0.061	-10000	0	-0.32	13	13
TRAIL/TRAILR3	0.015	0.08	-10000	0	-0.32	22	22
TRAIL/TRAILR1	0.008	0.089	-10000	0	-0.29	38	38
TRAIL/TRAILR4	0.022	0.06	-10000	0	-0.3	13	13
TRAIL/TRAILR1/DAP3/GTP	0.027	0.073	-10000	0	-0.23	35	35
IKK complex	0.014	0.044	-10000	0	-10000	0	0
RIPK1	0.026	0.003	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.019	0.003	-10000	0	-10000	0	0
MAPK3	0.004	0.048	-10000	0	-0.3	11	11
MAP3K1	0.02	0.049	-10000	0	-0.25	2	2
TRAILR4 (trimer)	0.019	0.038	-10000	0	-0.17	15	15
TRADD	0.025	0.02	-10000	0	-0.43	1	1
TRAILR1 (trimer)	0	0.098	-10000	0	-0.43	24	24
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.011	0.059	-10000	0	-0.21	31	31
CFLAR	0.026	0.007	-10000	0	-10000	0	0
MAPK1	0.004	0.048	-10000	0	-0.3	11	11
TRAIL/TRAILR1/FADD/TRADD/RIP	0.05	0.077	-10000	0	-0.22	33	33
mol:ceramide	0.007	0.031	-10000	0	-0.18	13	13
FADD	0.025	0.005	-10000	0	-10000	0	0
MAPK8	0.013	0.059	0.2	2	-0.28	4	6
TRAF2	0.026	0.005	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.009	0.074	-10000	0	-0.25	31	31
CHUK	0.025	0.005	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	0.028	0.078	-10000	0	-0.26	33	33
DAP3	0.026	0.004	-10000	0	-10000	0	0
CASP10	-0.001	0.062	0.16	17	-0.27	11	28
JNK cascade	0.022	0.06	-10000	0	-0.3	13	13
TRAIL (trimer)	0.012	0.07	-10000	0	-0.26	25	25
TNFRSF10C	0.009	0.074	-10000	0	-0.25	31	31
TRAIL/TRAILR1/DAP3/GTP/FADD	0.037	0.072	-10000	0	-0.22	33	33
TRAIL/TRAILR2/FADD	0.042	0.051	-10000	0	-0.26	13	13
cell death	0.007	0.031	-10000	0	-0.18	13	13
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.021	0.04	-10000	0	-0.22	13	13
TRAILR2 (trimer)	0.022	0.036	-10000	0	-0.35	4	4
CASP8	0.013	0.043	-10000	0	-0.77	1	1
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.063	0.053	-10000	0	-0.22	13	13

×

Regulation of p38-alpha and p38-beta

Figure S98. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S98. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.034	0.008	-10000	0	-10000	0	0
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0.026	0.003	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.024	0.021	-10000	0	-0.43	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.026	0.01	-10000	0	-10000	0	0
RAC1-CDC42/GTP/PAK family	-0.021	0.069	-10000	0	-0.19	62	62
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.022	0.04	-10000	0	-0.43	4	4
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	0.025	0.005	-10000	0	-10000	0	0
FYN	0.025	0.005	-10000	0	-10000	0	0
MAP3K12	0.026	0.004	-10000	0	-10000	0	0
FGR	0.021	0.015	-10000	0	-0.13	3	3
p38 alpha/TAB1	-0.034	0.071	-10000	0	-0.3	18	18
PRKG1	-0.009	0.12	-10000	0	-0.38	43	43
DUSP8	0.02	0.039	-10000	0	-0.43	3	3
PGK/cGMP/p38 alpha	-0.011	0.11	-10000	0	-0.31	25	25
apoptosis	-0.033	0.068	-10000	0	-0.28	18	18
RAL/GTP	0.031	0.012	-10000	0	-10000	0	0
LYN	0.021	0.035	-10000	0	-0.43	2	2
DUSP1	0.008	0.077	-10000	0	-0.25	32	32
PAK1	0.008	0.061	-10000	0	-0.43	5	5
SRC	0.025	0.005	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.056	0.026	-10000	0	-10000	0	0
TRAF6	0.024	0.021	-10000	0	-0.43	1	1
RAC1	0.023	0.009	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
mol:cGMP	0	0	-10000	0	-10000	0	0
CCM2	0.022	0.009	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0.026	0.016	-10000	0	-10000	0	0
MAPK11	0	0.13	0.28	26	-0.33	23	49
BLK	-0.03	0.11	-10000	0	-0.43	29	29
HCK	0.014	0.063	-10000	0	-0.27	19	19
MAP2K3	0.026	0.01	-10000	0	-10000	0	0
DUSP16	0.025	0.005	-10000	0	-10000	0	0
DUSP10	0.015	0.065	-10000	0	-0.43	10	10
TRAF6/MEKK3	0.031	0.015	-10000	0	-0.23	1	1
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.009	0.11	0.24	26	-0.35	14	40
positive regulation of innate immune response	0.003	0.14	0.3	27	-0.38	21	48
LCK	-0.019	0.11	-10000	0	-0.43	30	30
p38alpha-beta/MKP7	0.013	0.14	0.31	25	-0.37	18	43
p38alpha-beta/MKP5	0.006	0.14	0.29	23	-0.36	25	48
PGK/cGMP	-0.005	0.082	-10000	0	-0.3	36	36
PAK2	0.026	0.004	-10000	0	-10000	0	0
p38alpha-beta/MKP1	0.007	0.15	0.31	24	-0.38	22	46
CDC42	0.022	0.01	-10000	0	-10000	0	0
RALB	0.026	0.002	-10000	0	-10000	0	0
RALA	0.023	0.009	-10000	0	-10000	0	0
PAK3	-0.055	0.16	-10000	0	-0.43	80	80

×

Class I PI3K signaling events

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
ARF5/GTP	0	0.04	0.29	2	-10000	0	2
DAPP1	-0.033	0.14	0.26	6	-0.4	38	44
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.074	0.22	0.32	7	-0.52	62	69
mol:DAG	-0.02	0.099	0.29	13	-0.26	23	36
HRAS	0.025	0.008	-10000	0	-10000	0	0
RAP1A	0.022	0.011	-10000	0	-10000	0	0
ARF5/GDP	0.021	0.06	0.2	3	-0.31	6	9
PLCG2	0.018	0.055	-10000	0	-0.29	13	13
PLCG1	0.025	0.005	-10000	0	-10000	0	0
ARF5	0.02	0.011	-10000	0	-10000	0	0
mol:GTP	0	0.051	0.21	17	-10000	0	17
ARF1/GTP	0.003	0.035	0.24	4	-10000	0	4
RHOA	0.026	0.004	-10000	0	-10000	0	0
YES1	0.022	0.04	-10000	0	-0.43	4	4
RAP1A/GTP	-0.004	0.041	0.17	18	-10000	0	18
ADAP1	-0.006	0.046	0.25	4	-0.21	5	9
ARAP3	0	0.05	0.21	17	-10000	0	17
INPPL1	0.025	0.005	-10000	0	-10000	0	0
PREX1	0.016	0.063	-10000	0	-0.43	10	10
ARHGEF6	0.023	0.04	-10000	0	-0.43	4	4
ARHGEF7	0.025	0.005	-10000	0	-10000	0	0
ARF1	0.026	0.004	-10000	0	-10000	0	0
NRAS	0.022	0.011	-10000	0	-10000	0	0
FYN	0.025	0.005	-10000	0	-10000	0	0
ARF6	0.026	0.004	-10000	0	-10000	0	0
FGR	0.021	0.015	-10000	0	-0.13	3	3
mol:Ca2+	-0.01	0.059	0.23	11	-0.14	14	25
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.026	0.004	-10000	0	-10000	0	0
ZAP70	-0.004	0.098	-10000	0	-0.43	22	22
mol:IP3	-0.017	0.076	0.26	12	-0.2	18	30
LYN	0.021	0.035	-10000	0	-0.43	2	2
ARF1/GDP	0.033	0.07	0.21	4	-0.3	9	13
RhoA/GDP	0.037	0.06	0.24	14	-10000	0	14
PDK1/Src/Hsp90	0.048	0.024	-10000	0	-0.26	2	2
BLNK	-0.021	0.13	-10000	0	-0.43	49	49
actin cytoskeleton reorganization	0.022	0.1	0.28	25	-0.38	9	34
SRC	0.025	0.005	-10000	0	-10000	0	0
PLEKHA2	-0.009	0.02	-10000	0	-0.26	3	3
RAC1	0.023	0.009	-10000	0	-10000	0	0
PTEN	0.022	0.013	-10000	0	-10000	0	0
HSP90AA1	0.025	0.005	-10000	0	-10000	0	0
ARF6/GTP	-0.004	0.043	0.23	6	-10000	0	6
RhoA/GTP	0.005	0.054	0.21	16	-10000	0	16
Src family/SYK family/BLNK-LAT	-0.067	0.17	-10000	0	-0.43	62	62
BLK	-0.03	0.11	-10000	0	-0.43	29	29
PDPK1	0.024	0.028	-10000	0	-0.43	2	2
CYTH1	-0.004	0.043	0.24	4	-10000	0	4
HCK	0.014	0.063	-10000	0	-0.27	19	19
CYTH3	-0.003	0.041	0.28	3	-10000	0	3
CYTH2	-0.004	0.043	0.27	4	-10000	0	4
KRAS	0.026	0.007	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.008	0.08	0.21	1	-0.4	16	17
SGK1	-0.001	0.1	-10000	0	-0.38	30	30
INPP5D	0.022	0.037	-10000	0	-0.28	6	6
mol:GDP	0.022	0.072	0.2	11	-0.31	9	20
SOS1	0.026	0.002	-10000	0	-10000	0	0
SYK	0.009	0.083	-10000	0	-0.35	23	23
ARF6/GDP	0.033	0.064	0.26	17	-0.22	1	18
mol:PI-3-4-5-P3	-0.011	0.027	0.19	6	-10000	0	6
ARAP3/RAP1A/GTP	-0.004	0.041	0.17	18	-10000	0	18
VAV1	0.005	0.09	-10000	0	-0.34	29	29
mol:PI-3-4-P2	0.01	0.026	-10000	0	-0.3	3	3
RAS family/GTP/PI3K Class I	0.032	0.04	0.19	8	-10000	0	8
PLEKHA1	-0.009	0.021	-10000	0	-0.26	3	3
Rac1/GDP	0.024	0.063	0.2	3	-0.3	7	10
LAT	0.003	0.1	-10000	0	-0.43	26	26
Rac1/GTP	0.019	0.075	-10000	0	-0.42	9	9
ITK	-0.022	0.064	0.26	4	-0.21	19	23
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.035	0.12	0.35	8	-0.37	25	33
LCK	-0.019	0.11	-10000	0	-0.43	30	30
BTK	-0.01	0.055	0.27	4	-0.21	2	6

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.12	0.37	-9999	-1.1	58	58
RAD9A	0.025	0.005	-9999	-10000	0	0
AP1	-0.016	0.1	-9999	-0.28	56	56
IFNAR2	0.02	0.018	-9999	-10000	0	0
AKT1	0.004	0.035	-9999	-0.24	1	1
ER alpha/Oestrogen	0.005	0.05	-9999	-0.25	15	15
NFX1/SIN3/HDAC complex	-0.004	0.072	-9999	-0.23	10	10
EGF	-0.014	0.11	-9999	-0.41	35	35
SMG5	0.025	0.005	-9999	-10000	0	0
SMG6	0.026	0.002	-9999	-10000	0	0
SP3/HDAC2	0.03	0.027	-9999	-10000	0	0
TERT/c-Abl	-0.099	0.34	-9999	-1	59	59
SAP18	0.025	0.006	-9999	-10000	0	0
MRN complex	0.046	0.018	-9999	-10000	0	0
WT1	0	0.046	-9999	-0.16	5	5
WRN	0.023	0.035	-9999	-0.43	3	3
SP1	0.019	0.022	-9999	-10000	0	0
SP3	0.022	0.015	-9999	-10000	0	0
TERF2IP	0.026	0.003	-9999	-10000	0	0
Telomerase/Nucleolin	-0.072	0.31	-9999	-0.9	58	58
Mad/Max	0.03	0.023	-9999	-10000	0	0
TERT	-0.13	0.39	-9999	-1.2	58	58
CCND1	-0.11	0.34	-9999	-0.99	63	63
MAX	0.021	0.015	-9999	-10000	0	0
RBBP7	0.025	0.004	-9999	-10000	0	0
RBBP4	0.021	0.022	-9999	-0.43	1	1
TERF2	0.021	0.006	-9999	-10000	0	0
PTGES3	0.026	0.003	-9999	-10000	0	0
SIN3A	0.025	0.003	-9999	-10000	0	0
Telomerase/911	0.031	0.056	-9999	-0.32	3	3
CDKN1B	0.009	0.024	-9999	-10000	0	0
RAD1	0.026	0.003	-9999	-10000	0	0
XRCC5	0.026	0.003	-9999	-10000	0	0
XRCC6	0.026	0.004	-9999	-10000	0	0
SAP30	0.025	0.005	-9999	-10000	0	0
TRF2/PARP2	0.036	0.007	-9999	-10000	0	0
UBE3A	0.022	0.014	-9999	-10000	0	0
JUN	0.015	0.025	-9999	-0.13	9	9
E6	-0.001	0.005	-9999	-10000	0	0
HPV-16 E6/E6AP	0.015	0.015	-9999	-10000	0	0
FOS	-0.035	0.14	-9999	-0.37	60	60
IFN-gamma/IRF1	0.025	0.035	-9999	-10000	0	0
PARP2	0.026	0.004	-9999	-10000	0	0
BLM	-0.008	0.1	-9999	-0.25	62	62
Telomerase	-0.016	0.098	-9999	-0.33	32	32
IRF1	0.017	0.036	-9999	-10000	0	0
ESR1	0.01	0.07	-9999	-0.26	25	25
KU/TER	0.038	0.007	-9999	-10000	0	0
ATM/TRF2	0.037	0.009	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0.072	-9999	-0.31	4	4
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0	0.074	-9999	-0.31	4	4
HDAC1	0.022	0.01	-9999	-10000	0	0
HDAC2	0.019	0.022	-9999	-10000	0	0
ATM	0.01	0.002	-9999	-10000	0	0
SMAD3	0.012	0.016	-9999	-0.3	1	1
ABL1	0.025	0.005	-9999	-10000	0	0
MXD1	0.022	0.015	-9999	-10000	0	0
MRE11A	0.025	0.006	-9999	-10000	0	0
HUS1	0.023	0.009	-9999	-10000	0	0
RPS6KB1	0.025	0.005	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.086	0.34	-9999	-1	54	54
NR2F2	0.017	0.061	-9999	-0.22	24	24
MAPK3	-0.014	0.01	-9999	-10000	0	0
MAPK1	-0.013	0.009	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.021	0.022	-9999	-0.42	1	1
NFKB1	0.026	0.004	-9999	-10000	0	0
HNRNPC	0.026	0.004	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.01	0.002	-9999	-10000	0	0
NBN	0.024	0.007	-9999	-10000	0	0
EGFR	-0.02	0.12	-9999	-0.4	46	46
mol:Oestrogen	-0.001	0.003	-9999	-10000	0	0
EGF/EGFR	-0.025	0.12	-9999	-0.32	69	69
MYC	0.001	0.088	-9999	-0.4	22	22
IL2	0.007	0.024	-9999	-10000	0	0
KU	0.038	0.007	-9999	-10000	0	0
RAD50	0.026	0.003	-9999	-10000	0	0
HSP90AA1	0.025	0.005	-9999	-10000	0	0
TGFB1	0.021	0.022	-9999	-0.42	1	1
TRF2/BLM	0.012	0.072	-9999	-0.28	24	24
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.09	0.35	-9999	-1	58	58
SP1/HDAC2	0.029	0.032	-9999	-10000	0	0
PINX1	0.025	0.005	-9999	-10000	0	0
Telomerase/EST1A	-0.071	0.31	-9999	-0.9	58	58
Smad3/Myc	0.01	0.058	-9999	-0.27	19	19
911 complex	0.044	0.021	-9999	-10000	0	0
IFNG	0.015	0.021	-9999	-0.14	2	2
Telomerase/PinX1	-0.073	0.31	-9999	-0.9	58	58
Telomerase/AKT1/mTOR/p70S6K	-0.01	0.1	-9999	-0.48	8	8
SIN3B	0.025	0.006	-9999	-10000	0	0
YWHAE	0.026	0.002	-9999	-10000	0	0
Telomerase/EST1B	-0.072	0.31	-9999	-0.9	58	58
response to DNA damage stimulus	0.006	0.009	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0.065	0.026	-9999	-10000	0	0
TRF2/WRN	0.033	0.025	-9999	-0.28	3	3
Telomerase/hnRNP C1/C2	-0.07	0.31	-9999	-0.9	58	58
E2F1	0.009	0.058	-9999	-0.21	24	24
ZNFX1	0.025	0.005	-9999	-10000	0	0
PIF1	-0.01	0.11	-9999	-0.27	61	61
NCL	0.026	0.004	-9999	-10000	0	0
DKC1	0.026	0.003	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.026	0.056	-10000	0	-10000	0	0
epithelial cell differentiation	-0.014	0.086	-10000	0	-0.38	5	5
ITCH	0.03	0.013	-10000	0	-10000	0	0
WWP1	0.017	0.063	-10000	0	-10000	0	0
FYN	0.025	0.005	-10000	0	-10000	0	0
EGFR	-0.016	0.12	-10000	0	-0.4	46	46
PRL	-0.011	0.016	-10000	0	-0.13	2	2
neuron projection morphogenesis	-0.019	0.11	0.28	18	-0.4	2	20
PTPRZ1	0.016	0.046	-10000	0	-0.43	5	5
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.008	0.11	-10000	0	-0.34	5	5
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.039	0.1	-10000	0	-0.32	14	14
ADAM17	0.025	0.046	-10000	0	-0.42	5	5
ErbB4/ErbB4	0.006	0.051	-10000	0	-0.36	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	0.013	0.082	-10000	0	-0.34	10	10
NCOR1	0.024	0.028	-10000	0	-0.43	2	2
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.027	0.1	-10000	0	-0.34	8	8
GRIN2B	-0.068	0.13	0.24	10	-0.36	40	50
ErbB4/ErbB2/betacellulin	-0.001	0.096	-10000	0	-0.34	12	12
STAT1	0.021	0.028	-10000	0	-0.13	16	16
HBEGF	0.023	0.022	-10000	0	-0.13	10	10
PRLR	0.006	0.088	-10000	0	-0.32	30	30
E4ICDs/ETO2	0.022	0.065	-10000	0	-0.35	3	3
axon guidance	-0.024	0.079	-10000	0	-0.38	8	8
NEDD4	0.025	0.041	-10000	0	-0.22	10	10
Prolactin receptor/Prolactin receptor/Prolactin	0.016	0.065	-10000	0	-0.31	18	18
CBFA2T3	0.02	0.053	-10000	0	-0.43	7	7
ErbB4/ErbB2/HBEGF	0.027	0.052	-10000	0	-0.28	3	3
MAPK3	-0.017	0.11	0.27	12	-0.41	2	14
STAT1 (dimer)	0.026	0.059	-10000	0	-0.32	1	1
MAPK1	-0.017	0.11	0.27	12	-0.41	2	14
JAK2	0.025	0.006	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.037	0.1	-10000	0	-0.34	8	8
NRG1	-0.061	0.13	-10000	0	-0.31	101	101
NRG3	0.001	0.1	-10000	0	-0.43	27	27
NRG2	0.025	0.02	-10000	0	-0.43	1	1
NRG4	0.001	0.079	-10000	0	-0.43	12	12
heart development	-0.024	0.079	-10000	0	-0.38	8	8
neural crest cell migration	-0.036	0.099	-10000	0	-0.33	8	8
ERBB2	0.01	0.036	-10000	0	-0.3	6	6
WWOX/E4ICDs	0.025	0.057	-10000	0	-0.32	1	1
SHC1	0.024	0.014	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	0.004	0.1	-10000	0	-0.34	17	17
apoptosis	-0.001	0.11	0.37	32	-10000	0	32
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	0.026	0.057	-10000	0	-0.37	1	1
ErbB4/ErbB2/epiregulin	0.025	0.056	-10000	0	-0.31	4	4
ErbB4/ErbB4/betacellulin/betacellulin	-0.005	0.1	-10000	0	-0.38	10	10
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.045	0.076	-10000	0	-0.32	1	1
MDM2	0.01	0.055	0.25	4	-0.32	1	5
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.031	0.1	-10000	0	-0.29	12	12
STAT5A	-0.028	0.084	-10000	0	-0.4	7	7
ErbB4/EGFR/neuregulin 1 beta	-0.045	0.12	-10000	0	-0.35	28	28
DLG4	0.023	0.021	-10000	0	-0.13	9	9
GRB2/SHC	0.036	0.014	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	0.022	0.056	-10000	0	-0.5	1	1
STAT5A (dimer)	-0.007	0.097	-10000	0	-0.4	5	5
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.012	0.083	-10000	0	-0.38	6	6
LRIG1	0.015	0.069	-10000	0	-0.43	12	12
EREG	0.008	0.036	-10000	0	-0.13	24	24
BTC	-0.04	0.14	-10000	0	-0.33	87	87
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.026	0.075	-10000	0	-0.38	8	8
ERBB4	0.006	0.051	-10000	0	-0.36	1	1
STAT5B	0.026	0.003	-10000	0	-10000	0	0
YAP1	-0.015	0.13	-10000	0	-0.55	27	27
GRB2	0.025	0.006	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0.021	0.067	-10000	0	-0.31	5	5
glial cell differentiation	-0.021	0.056	0.5	1	-10000	0	1
WWOX	0.026	0.003	-10000	0	-10000	0	0
cell proliferation	-0.071	0.14	-10000	0	-0.47	19	19

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.004	0.15	0.24	5	-0.38	21	26
CaM/Ca2+	0.018	0.006	-10000	0	-10000	0	0
AKT1	0.025	0.005	-10000	0	-10000	0	0
AKT2	0.022	0.01	-10000	0	-10000	0	0
STXBP4	0.025	0.02	-10000	0	-0.43	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	-0.013	0.15	0.23	21	-0.34	42	63
YWHAZ	0.023	0.008	-10000	0	-10000	0	0
CALM1	0.025	0.009	-10000	0	-0.13	1	1
YWHAQ	0.026	0.003	-10000	0	-10000	0	0
TBC1D4	0.013	0.003	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.019	0.033	-10000	0	-10000	0	0
YWHAB	0.025	0.005	-10000	0	-10000	0	0
SNARE/Synip	0.051	0.017	-10000	0	-0.26	1	1
YWHAG	0.019	0.024	-10000	0	-0.13	11	11
ASIP	-0.04	0.14	-10000	0	-0.32	94	94
PRKCI	0.026	0.003	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0.018	0.006	-10000	0	-10000	0	0
RHOQ	0.026	0.002	-10000	0	-10000	0	0
GYS1	0.01	0.016	0.24	1	-0.25	1	2
PRKCZ	0.007	0.076	-10000	0	-0.43	14	14
TRIP10	0.021	0.041	-10000	0	-0.37	5	5
TC10/GTP/CIP4/Exocyst	0.032	0.024	-10000	0	-0.26	3	3
AS160/14-3-3	0.01	0.054	-10000	0	-0.51	1	1
VAMP2	0.026	0.002	-10000	0	-10000	0	0
SLC2A4	-0.018	0.16	0.26	6	-0.39	39	45
STX4	0.026	0.002	-10000	0	-10000	0	0
GSK3B	0.017	0.016	-10000	0	-0.29	1	1
SFN	-0.023	0.11	-10000	0	-0.22	90	90
LNPEP	0.008	0.088	-10000	0	-0.43	20	20
YWHAE	0.026	0.002	-10000	0	-10000	0	0

×

IFN-gamma 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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.045	0.033	0.2	1	-10000	0	1
positive regulation of NF-kappaB transcription factor activity	0	0.001	-10000	0	-10000	0	0
CRKL	0.026	0.008	-10000	0	-0.13	1	1
STAT1 (dimer)/Cbp/p300	0.038	0.05	0.29	2	-0.23	2	4
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.04	0.025	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.023	0.074	-10000	0	-0.21	40	40
CaM/Ca2+	0.046	0.034	-10000	0	-10000	0	0
RAP1A	0.021	0.01	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	0.019	0.033	-10000	0	-10000	0	0
AKT1	0.002	0.039	0.24	3	-10000	0	3
MAP2K1	-0.002	0.036	0.23	4	-10000	0	4
MAP3K11	0.011	0.032	0.24	3	-10000	0	3
IFNGR1	0.026	0.007	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.059	0.19	-10000	0	-0.41	101	101
Rap1/GTP	0.012	0.017	-10000	0	-10000	0	0
CRKL/C3G	0.037	0.01	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.056	0.035	-10000	0	-10000	0	0
CEBPB	0.016	0.11	0.29	2	-0.46	18	20
STAT3	0.026	0.003	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.031	0.15	-10000	0	-1.1	8	8
STAT1	0.01	0.036	0.24	4	-10000	0	4
CALM1	0.025	0.009	-10000	0	-0.13	1	1
IFN-gamma (dimer)	0.011	0.021	-10000	0	-0.13	5	5
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
STAT1 (dimer)/PIAS1	0.022	0.043	0.26	3	-0.2	4	7
CEBPB/PTGES2/Cbp/p300	0.028	0.075	-10000	0	-0.32	15	15
mol:Ca2+	0.042	0.031	-10000	0	-10000	0	0
MAPK3	0.016	0.065	-10000	0	-0.74	2	2
STAT1 (dimer)	-0.021	0.1	-10000	0	-0.28	38	38
MAPK1	0.011	0.089	-10000	0	-0.69	6	6
JAK2	0.025	0.007	-10000	0	-10000	0	0
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
JAK1	0.022	0.011	-10000	0	-10000	0	0
CAMK2D	0.025	0.02	-10000	0	-0.43	1	1
DAPK1	0.011	0.12	0.32	3	-0.59	18	21
SMAD7	-0.009	0.046	0.17	3	-0.14	9	12
CBL/CRKL/C3G	0.035	0.032	0.29	1	-10000	0	1
PI3K	0.044	0.035	-10000	0	-10000	0	0
IFNG	0.011	0.021	-10000	0	-0.13	5	5
apoptosis	0.007	0.11	0.26	4	-0.44	23	27
CAMK2G	0.024	0.021	-10000	0	-0.43	1	1
STAT3 (dimer)	0.026	0.003	-10000	0	-10000	0	0
CAMK2A	-0.099	0.17	-10000	0	-0.26	222	222
CAMK2B	-0.018	0.12	-10000	0	-0.43	33	33
FRAP1	-0.002	0.036	0.2	5	-10000	0	5
PRKCD	-0.008	0.055	0.22	5	-0.2	18	23
RAP1B	0.026	0.004	-10000	0	-10000	0	0
negative regulation of cell growth	-0.023	0.074	-10000	0	-0.21	40	40
PTPN2	0.026	0.004	-10000	0	-10000	0	0
EP300	0.022	0.04	-10000	0	-0.43	4	4
IRF1	-0.001	0.062	0.26	4	-0.31	7	11
STAT1 (dimer)/PIASy	0.022	0.041	0.28	3	-10000	0	3
SOCS1	0.001	0.17	-10000	0	-1.4	8	8
mol:GDP	0.032	0.03	0.27	1	-10000	0	1
CASP1	-0.012	0.058	0.2	3	-0.24	14	17
PTGES2	0.025	0.005	-10000	0	-10000	0	0
IRF9	0.022	0.041	0.15	8	-0.16	4	12
mol:PI-3-4-5-P3	0.031	0.028	-10000	0	-10000	0	0
RAP1/GDP	0.028	0.025	-10000	0	-10000	0	0
CBL	0.01	0.031	0.24	3	-10000	0	3
MAP3K1	0.01	0.033	0.24	3	-10000	0	3
PIAS1	0.022	0.04	-10000	0	-0.43	4	4
PIAS4	0.025	0.006	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.023	0.074	-10000	0	-0.21	40	40
PTPN11	0.013	0.029	0.18	7	-10000	0	7
CREBBP	0.026	0.003	-10000	0	-10000	0	0
RAPGEF1	0.025	0.005	-10000	0	-10000	0	0

×

PDGFR-beta 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
S1P1/Sphingosine-1-phosphate	0.015	0.075	0.31	7	-0.3	10	17
PDGFB-D/PDGFRB/SLAP	0.021	0.061	-10000	0	-0.3	15	15
PDGFB-D/PDGFRB/APS/CBL	0.034	0.044	-10000	0	-0.26	8	8
AKT1	0.007	0.071	0.33	11	-10000	0	11
mol:PI-4-5-P2	0	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.02	0.082	0.32	10	-0.31	8	18
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
FGR	-0.041	0.14	0.34	2	-0.37	74	76
mol:Ca2+	0.019	0.073	0.29	15	-0.3	3	18
MYC	0.032	0.21	0.4	32	-0.75	22	54
SHC1	0.024	0.014	-10000	0	-10000	0	0
HRAS/GDP	0.03	0.029	0.18	9	-10000	0	9
LRP1/PDGFRB/PDGFB	0.051	0.014	-10000	0	-10000	0	0
GRB10	0.021	0.03	-10000	0	-0.43	2	2
PTPN11	0.026	0.003	-10000	0	-10000	0	0
GO:0007205	0.018	0.074	0.29	15	-0.3	3	18
PTEN	0.025	0.006	-10000	0	-10000	0	0
GRB2	0.025	0.006	-10000	0	-10000	0	0
GRB7	0.001	0.044	-10000	0	-0.13	41	41
PDGFB-D/PDGFRB/SHP2	0.038	0.012	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB10	0.031	0.027	-10000	0	-0.31	2	2
cell cycle arrest	0.021	0.06	-10000	0	-0.3	15	15
HRAS	0.025	0.006	-10000	0	-10000	0	0
HIF1A	0.005	0.066	0.31	11	-10000	0	11
GAB1	0.012	0.091	0.31	14	-0.36	5	19
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	0.015	0.096	0.34	18	-0.32	6	24
PDGFB-D/PDGFRB	0.049	0.022	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.038	0.011	-10000	0	-10000	0	0
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.015	0.079	0.22	2	-0.33	11	13
positive regulation of MAPKKK cascade	0.037	0.012	-10000	0	-10000	0	0
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
mol:IP3	0.019	0.074	0.3	15	-0.31	3	18
E5	0	0.001	-10000	0	-10000	0	0
CSK	0.025	0.007	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7	0.026	0.036	-10000	0	-0.18	1	1
SHB	0.026	0.004	-10000	0	-10000	0	0
BLK	-0.018	0.12	0.31	1	-0.47	31	32
PTPN2	0.026	0.006	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.037	0.012	-10000	0	-10000	0	0
BCAR1	0.025	0.02	-10000	0	-0.43	1	1
VAV2	0.015	0.1	0.34	13	-0.36	10	23
CBL	0.025	0.007	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.037	0.012	-10000	0	-10000	0	0
LCK	-0.072	0.18	0.34	2	-0.41	104	106
PDGFRB	0.025	0.014	-10000	0	-0.15	1	1
ACP1	0.026	0.004	-10000	0	-10000	0	0
HCK	0.003	0.083	0.31	1	-0.58	9	10
ABL1	0.006	0.094	0.29	17	-0.35	9	26
PDGFB-D/PDGFRB/CBL	0.015	0.093	0.3	13	-0.41	4	17
PTPN1	0.025	0.007	-10000	0	-10000	0	0
SNX15	0.025	0.005	-10000	0	-10000	0	0
STAT3	0.026	0.003	-10000	0	-10000	0	0
STAT1	0.021	0.028	-10000	0	-0.13	16	16
cell proliferation	0.035	0.19	0.35	46	-0.66	22	68
SLA	0.006	0.077	-10000	0	-0.28	28	28
actin cytoskeleton reorganization	0.033	0.047	0.33	4	-10000	0	4
SRC	0.011	0.025	-10000	0	-10000	0	0
PI3K	0.006	0.024	-10000	0	-0.21	4	4
PDGFB-D/PDGFRB/GRB7/SHC	0.044	0.031	-10000	0	-0.21	1	1
SH2B2	0.014	0.057	-10000	0	-0.43	8	8
PLCgamma1/SPHK1	0.02	0.084	0.33	10	-0.32	8	18
LYN	0.01	0.054	0.3	1	-0.5	4	5
LRP1	0.026	0.004	-10000	0	-10000	0	0
SOS1	0.026	0.002	-10000	0	-10000	0	0
STAT5B	0.026	0.003	-10000	0	-10000	0	0
STAT5A	0.016	0.066	-10000	0	-0.43	11	11
NCK1-2/p130 Cas	0.072	0.032	-10000	0	-0.22	2	2
SPHK1	0.005	0.086	-10000	0	-0.43	17	17
EDG1	0	0.003	-10000	0	-10000	0	0
mol:DAG	0.019	0.074	0.3	15	-0.31	3	18
PLCG1	0.018	0.075	0.3	15	-0.32	2	17
NHERF/PDGFRB	0.048	0.031	-10000	0	-0.26	4	4
YES1	0.001	0.085	-10000	0	-0.49	13	13
cell migration	0.047	0.031	-10000	0	-0.26	4	4
SHC/Grb2/SOS1	0.07	0.03	-10000	0	-10000	0	0
SLC9A3R2	0.026	0.01	-10000	0	-0.13	2	2
SLC9A3R1	0.022	0.04	-10000	0	-0.43	4	4
NHERF1-2/PDGFRB/PTEN	0.059	0.034	-10000	0	-0.24	4	4
FYN	0.002	0.078	0.3	1	-0.41	14	15
DOK1	0.015	0.024	0.18	7	-0.24	1	8
HRAS/GTP	0.018	0.005	-10000	0	-10000	0	0
PDGFB	0.026	0.004	-10000	0	-10000	0	0
RAC1	0.031	0.15	0.4	26	-0.44	21	47
PRKCD	0.006	0.066	0.18	17	-0.24	26	43
FER	0.009	0.06	0.19	16	-0.24	20	36
MAPKKK cascade	0.006	0.066	0.38	7	-10000	0	7
RASA1	0.019	0.033	0.19	16	-10000	0	16
NCK1	0.025	0.02	-10000	0	-0.43	1	1
NCK2	0.026	0.002	-10000	0	-10000	0	0
p62DOK/Csk	0.033	0.026	0.18	4	-0.22	1	5
PDGFB-D/PDGFRB/SHB	0.037	0.011	-10000	0	-10000	0	0
chemotaxis	0.006	0.093	0.29	17	-0.34	9	26
STAT1-3-5/STAT1-3-5	0.055	0.045	-10000	0	-0.22	10	10
Bovine Papilomavirus E5/PDGFRB	0.017	0.012	-10000	0	-10000	0	0
PTPRJ	0.025	0.005	-10000	0	-10000	0	0

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.028	0.023	-10000	0	-10000	0	0
FBXW11	0.026	0.004	-10000	0	-10000	0	0
NF kappa B1 p50/c-Rel	0.016	0.054	-10000	0	-0.26	18	18
NF kappa B1 p50/RelA/I kappa B alpha	0.006	0.082	0.2	2	-0.29	14	16
NFKBIA	-0.014	0.073	-10000	0	-0.23	46	46
MAPK14	0.026	0.003	-10000	0	-10000	0	0
NF kappa B1 p105/p50	0.027	0.008	-10000	0	-10000	0	0
ARRB2	0.014	0.002	-10000	0	-10000	0	0
REL	0.007	0.086	-10000	0	-0.32	28	28
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	0.021	0.019	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	0.027	0.008	-10000	0	-10000	0	0
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
NF kappa B1 p50 dimer	0.02	0.011	0.25	1	-10000	0	1
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
NFKB1	0.013	0.003	-10000	0	-10000	0	0
RELA	0.025	0.005	-10000	0	-10000	0	0
positive regulation of anti-apoptosis	-0.009	0.077	-10000	0	-0.22	39	39
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.009	0.082	0.2	1	-0.28	14	15
SRC	0.025	0.005	-10000	0	-10000	0	0
PI3K	0.038	0.007	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.009	0.077	-10000	0	-0.23	39	39
IKBKB	0.025	0.005	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.026	0.004	-10000	0	-10000	0	0
SYK	0.009	0.083	-10000	0	-0.35	23	23
I kappa B alpha/PIK3R1	-0.001	0.087	0.19	3	-0.3	16	19
cell death	0.008	0.079	0.19	1	-0.27	14	15
NF kappa B1 p105/c-Rel	0.016	0.054	-10000	0	-0.26	18	18
LCK	-0.019	0.11	-10000	0	-0.43	30	30
BCL3	0.018	0.024	-10000	0	-0.13	11	11

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	0.03	0.046	-10000	0	-0.2	13	13
TC10/GTP	0.031	0.04	-10000	0	-0.21	9	9
Insulin Receptor/Insulin/IRS1/Shp2	0.054	0.033	-10000	0	-0.22	4	4
HRAS	0.025	0.006	-10000	0	-10000	0	0
APS homodimer	0.014	0.057	-10000	0	-0.43	8	8
GRB14	-0.071	0.16	-10000	0	-0.25	180	180
FOXO3	-0.019	0.15	-10000	0	-0.61	31	31
AKT1	-0.034	0.089	0.34	7	-0.36	1	8
INSR	0.027	0.009	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.046	0.03	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.021	0.03	-10000	0	-0.43	2	2
SORBS1	0.023	0.035	-10000	0	-0.43	3	3
CRK	0.026	0.002	-10000	0	-10000	0	0
PTPN1	0.01	0.035	-10000	0	-10000	0	0
CAV1	0.005	0.039	0.18	11	-0.23	4	15
CBL/APS/CAP/Crk-II/C3G	0.049	0.052	-10000	0	-0.22	10	10
Insulin Receptor/Insulin/IRS1/NCK2	0.055	0.032	-10000	0	-0.22	4	4
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.044	0.028	-10000	0	-0.19	4	4
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.026	0.036	-10000	0	-0.42	1	1
RPS6KB1	-0.033	0.082	0.33	7	-0.33	1	8
PARD6A	0.026	0.002	-10000	0	-10000	0	0
CBL	0.025	0.007	-10000	0	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.016	0.04	-10000	0	-0.6	2	2
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.011	0.078	-10000	0	-0.27	2	2
HRAS/GTP	0.014	0.025	-10000	0	-0.21	3	3
Insulin Receptor	0.027	0.009	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.061	0.037	-10000	0	-0.21	4	4
PRKCI	0.019	0.048	-10000	0	-0.44	4	4
Insulin Receptor/Insulin/GRB14/PDK1	-0.019	0.084	-10000	0	-0.21	70	70
SHC1	0.024	0.014	-10000	0	-10000	0	0
negative regulation of MAPKKK cascade	0.038	0.045	-10000	0	-0.5	2	2
PI3K	0.055	0.031	-10000	0	-0.2	4	4
NCK2	0.026	0.002	-10000	0	-10000	0	0
RHOQ	0.026	0.002	-10000	0	-10000	0	0
mol:H2O2	0	0.004	-10000	0	-10000	0	0
HRAS/GDP	0.018	0.005	-10000	0	-10000	0	0
AKT2	-0.037	0.082	0.47	3	-0.29	2	5
PRKCZ	-0.042	0.15	-10000	0	-0.44	34	34
SH2B2	0.014	0.057	-10000	0	-0.43	8	8
SHC/SHIP	0.032	0.049	0.21	13	-0.21	7	20
F2RL2	-0.019	0.1	-10000	0	-0.19	104	104
TRIP10	0.021	0.041	-10000	0	-0.37	5	5
Insulin Receptor/Insulin/Shc	0.039	0.029	-10000	0	-0.22	4	4
TC10/GTP/CIP4/Exocyst	0.032	0.024	-10000	0	-0.26	3	3
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.062	0.037	-10000	0	-0.21	4	4
RAPGEF1	0.025	0.005	-10000	0	-10000	0	0
RASA1	0.026	0.003	-10000	0	-10000	0	0
NCK1	0.025	0.02	-10000	0	-0.43	1	1
CBL/APS/CAP/Crk-II	0.043	0.049	-10000	0	-0.23	10	10
TC10/GDP	0.019	0.002	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.047	0.038	-10000	0	-0.23	5	5
INPP5D	0.018	0.051	0.18	30	-0.22	7	37
SOS1	0.026	0.002	-10000	0	-10000	0	0
SGK1	-0.034	0.18	-10000	0	-0.75	31	31
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.026	0.003	-10000	0	-10000	0	0
IRS1	0.026	0.003	-10000	0	-10000	0	0
p62DOK/RasGAP	0.039	0.045	-10000	0	-0.51	2	2
INS	0.015	0.041	-10000	0	-0.43	4	4
mol:PI-3-4-P2	0.018	0.05	0.18	30	-0.22	7	37
GRB2	0.025	0.006	-10000	0	-10000	0	0
EIF4EBP1	-0.035	0.086	0.33	7	-0.25	8	15
PTPRA	0.027	0.008	-10000	0	-10000	0	0
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
TC10/GTP/CIP4	0.032	0.024	-10000	0	-0.26	3	3
PDPK1	0.024	0.028	-10000	0	-0.43	2	2
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.022	0.024	-10000	0	-0.21	4	4
Insulin Receptor/Insulin/IRS1	0.04	0.028	-10000	0	-0.22	4	4
Insulin Receptor/Insulin/IRS3	0.029	0.033	-10000	0	-0.31	4	4
Par3/Par6	0.047	0.061	-10000	0	-0.22	23	23

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.025	0.045	0.21	3	-0.27	3	6
BIRC5	-0.058	0.16	-10000	0	-0.43	74	74
NFKBIA	0.013	0.035	0.25	3	-0.24	2	5
CPEB1	0.013	0.074	-10000	0	-0.43	14	14
AKT1	0.013	0.033	0.23	2	-0.24	2	4
NDEL1	0.026	0.002	-10000	0	-10000	0	0
Aurora A/BRCA1	0.028	0.031	-10000	0	-0.22	2	2
NDEL1/TACC3	0.043	0.043	0.2	2	-0.23	4	6
GADD45A	0.012	0.042	-10000	0	-0.43	1	1
GSK3B	0.028	0.025	-10000	0	-0.44	1	1
PAK1/Aurora A	0.024	0.05	-10000	0	-0.25	7	7
MDM2	0.026	0.004	-10000	0	-10000	0	0
JUB	0	0	-10000	0	-10000	0	0
TPX2	-0.013	0.077	-10000	0	-0.3	30	30
TP53	0.017	0.052	-10000	0	-0.24	17	17
DLG7	0.013	0.03	-10000	0	-0.24	2	2
AURKAIP1	0.022	0.01	-10000	0	-10000	0	0
ARHGEF7	0.025	0.005	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.043	0.048	0.21	2	-0.25	4	6
G2/M transition of mitotic cell cycle	0.028	0.031	-10000	0	-0.22	2	2
AURKA	0.022	0.039	0.14	10	-0.29	2	12
AURKB	-0.043	0.13	-10000	0	-0.29	97	97
CDC25B	0.021	0.029	-10000	0	-0.23	2	2
G2/M transition checkpoint	0.012	0.026	-10000	0	-0.22	2	2
mRNA polyadenylation	0.022	0.051	-10000	0	-0.24	14	14
Aurora A/CPEB	0.023	0.051	-10000	0	-0.24	14	14
Aurora A/TACC1/TRAP/chTOG	0.058	0.039	-10000	0	-0.24	3	3
BRCA1	0.025	0.012	-10000	0	-0.13	3	3
centrosome duplication	0.024	0.05	-10000	0	-0.25	7	7
regulation of centrosome cycle	0.039	0.045	0.19	2	-0.23	4	6
spindle assembly	0.056	0.039	-10000	0	-0.24	3	3
TDRD7	0.025	0.021	-10000	0	-0.43	1	1
Aurora A/RasGAP/Survivin	0.018	0.09	0.2	3	-0.21	38	41
CENPA	-0.03	0.12	-10000	0	-0.38	49	49
Aurora A/PP2A	0.033	0.034	-10000	0	-0.24	2	2
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	0.016	0.036	0.18	1	-0.23	2	3
negative regulation of DNA binding	0.017	0.053	-10000	0	-0.24	17	17
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.037	0.008	-10000	0	-10000	0	0
RASA1	0.026	0.003	-10000	0	-10000	0	0
Ajuba/Aurora A	0.012	0.027	-10000	0	-0.22	2	2
mitotic prometaphase	0.011	0.035	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.022	0.039	0.14	10	-0.29	2	12
TACC1	0.025	0.005	-10000	0	-10000	0	0
TACC3	0.011	0.053	-10000	0	-0.43	3	3
Aurora A/Antizyme1	0.04	0.035	-10000	0	-0.22	2	2
Aurora A/RasGAP	0.033	0.032	-10000	0	-0.24	1	1
OAZ1	0.025	0.006	-10000	0	-10000	0	0
RAN	0.026	0.003	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	0.028	0.015	-10000	0	-10000	0	0
GIT1	0.026	0.002	-10000	0	-10000	0	0
GIT1/beta-PIX/PAK1	0.048	0.032	-10000	0	-0.26	4	4
Importin alpha/Importin beta/TPX2	-0.013	0.077	-10000	0	-0.3	30	30
PPP2R5D	0.026	0.002	-10000	0	-10000	0	0
Aurora A/TPX2	0.004	0.064	-10000	0	-0.21	31	31
PAK1	0.008	0.061	-10000	0	-0.43	5	5
CKAP5	0.025	0.005	-10000	0	-10000	0	0

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.025	0.013	-10000	0	-10000	0	0
alphaV beta3 Integrin	0.018	0.063	-10000	0	-0.3	12	12
PTK2	0.009	0.088	-10000	0	-0.35	14	14
positive regulation of JNK cascade	-0.007	0.092	-10000	0	-0.33	10	10
CDC42/GDP	0.02	0.12	-10000	0	-0.43	10	10
Rac1/GDP	0.004	0.12	-10000	0	-0.43	9	9
RAP1B	0.026	0.004	-10000	0	-10000	0	0
RAP1A	0.021	0.01	-10000	0	-10000	0	0
CTNNB1	0.026	0.004	-10000	0	-10000	0	0
CDC42/GTP	-0.002	0.11	-10000	0	-0.41	10	10
nectin-3/I-afadin	0.031	0.046	-10000	0	-0.3	9	9
RAPGEF1	0	0.12	0.29	1	-0.44	7	8
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.013	0.12	-10000	0	-0.48	8	8
PDGFB-D/PDGFRB	0.025	0.013	-10000	0	-10000	0	0
TLN1	0.002	0.017	-10000	0	-10000	0	0
Rap1/GTP	-0.006	0.083	-10000	0	-0.32	8	8
IQGAP1	0.02	0.043	-10000	0	-0.25	10	10
Rap1/GTP/I-afadin	0.037	0.025	-10000	0	-0.23	1	1
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.031	0.046	-10000	0	-0.3	9	9
PVR	0.022	0.01	-10000	0	-10000	0	0
Necl-5(dimer)	0.022	0.01	-10000	0	-10000	0	0
mol:GDP	-0.002	0.14	-10000	0	-0.53	10	10
MLLT4	0.024	0.021	-10000	0	-0.43	1	1
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
PI3K	0.066	0.043	-10000	0	-0.22	8	8
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.024	0.06	-10000	0	-0.3	16	16
positive regulation of lamellipodium assembly	-0.003	0.088	-10000	0	-0.33	7	7
PVRL1	0.011	0.077	-10000	0	-0.43	15	15
PVRL3	0.019	0.056	-10000	0	-0.43	8	8
PVRL2	0.02	0.023	-10000	0	-0.43	1	1
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
CDH1	-0.046	0.15	-10000	0	-0.43	59	59
CLDN1	0.01	0.073	-10000	0	-0.26	28	28
JAM-A/CLDN1	0.049	0.063	-10000	0	-0.24	20	20
SRC	-0.014	0.12	-10000	0	-0.53	9	9
ITGB3	-0.001	0.082	-10000	0	-0.19	64	64
nectin-1(dimer)/I-afadin/I-afadin	0.024	0.06	-10000	0	-0.3	16	16
FARP2	-0.01	0.15	-10000	0	-0.6	9	9
RAC1	0.023	0.009	-10000	0	-10000	0	0
CTNNA1	0.026	0.004	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.037	0.042	-10000	0	-0.26	7	7
nectin-1/I-afadin	0.024	0.06	-10000	0	-0.3	16	16
nectin-2/I-afadin	0.03	0.027	-10000	0	-0.3	2	2
RAC1/GTP/IQGAP1/filamentous actin	0.027	0.029	-10000	0	-0.26	4	4
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.033	0.067	-10000	0	-0.27	22	22
CDC42/GTP/IQGAP1/filamentous actin	0.027	0.028	-10000	0	-0.23	4	4
F11R	0.022	0.03	-10000	0	-0.43	1	1
positive regulation of filopodium formation	-0.007	0.092	-10000	0	-0.33	10	10
alphaV/beta3 Integrin/Talin	0.035	0.062	0.2	23	-0.22	12	35
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.03	0.027	-10000	0	-0.3	2	2
nectin-2(dimer)/I-afadin/I-afadin	0.03	0.027	-10000	0	-0.3	2	2
PIP5K1C	0.005	0.02	-10000	0	-0.16	7	7
VAV2	0.002	0.14	-10000	0	-0.53	9	9
RAP1/GDP	0.011	0.11	-10000	0	-0.38	10	10
ITGAV	0.026	0.002	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.037	0.044	-10000	0	-0.26	8	8
nectin-3(dimer)/I-afadin/I-afadin	0.031	0.046	-10000	0	-0.3	9	9
Rac1/GTP	-0.001	0.11	-10000	0	-0.4	7	7
PTPRM	0.01	0.025	-10000	0	-0.17	9	9
E-cadherin/beta catenin/alpha catenin	0.022	0.1	-10000	0	-0.23	60	60
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.022	0.01	-10000	0	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	-0.016	0.041	-10000	0	-0.26	13	13
SNTA1	-0.001	0.1	-10000	0	-0.43	27	27
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	-0.012	0.032	-10000	0	-0.26	7	7
MAPK12	-0.003	0.017	-10000	0	-0.22	3	3
CCND1	0	0.061	-10000	0	-0.41	11	11
p38 gamma/SNTA1	0.013	0.062	0.19	18	-0.21	25	43
MAP2K3	0.026	0.01	-10000	0	-10000	0	0
PKN1	0.025	0.005	-10000	0	-10000	0	0
G2/M transition checkpoint	-0.003	0.017	-10000	0	-0.22	3	3
MAP2K6	0.003	0.011	-10000	0	-0.24	1	1
MAPT	0.004	0.06	0.24	5	-0.23	19	24
MAPK13	0.001	0.053	-10000	0	-0.3	14	14
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.007	0.002	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.013	0.003	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.036	0.018	-10000	0	-10000	0	0
CDKN1B	0.014	0.063	-10000	0	-0.28	16	16
CDKN1A	0.002	0.066	-10000	0	-0.29	15	15
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.025	0.005	-10000	0	-10000	0	0
FOXO3	0.015	0.044	-10000	0	-0.28	9	9
AKT1	0.007	0.058	-10000	0	-0.3	18	18
BAD	0.025	0.005	-10000	0	-10000	0	0
AKT3	0.01	0.046	-10000	0	-0.48	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.011	0.062	-10000	0	-0.28	17	17
AKT1/ASK1	0.027	0.064	-10000	0	-0.27	18	18
BAD/YWHAZ	0.044	0.02	-10000	0	-10000	0	0
RICTOR	0.026	0.003	-10000	0	-10000	0	0
RAF1	0.026	0.004	-10000	0	-10000	0	0
JNK cascade	-0.026	0.062	0.26	18	-10000	0	18
TSC1	0.009	0.057	-10000	0	-0.28	17	17
YWHAZ	0.023	0.008	-10000	0	-10000	0	0
AKT1/RAF1	0.032	0.06	-10000	0	-0.28	15	15
EP300	0.022	0.04	-10000	0	-0.43	4	4
mol:GDP	0.011	0.06	-10000	0	-0.29	18	18
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.01	0.059	-10000	0	-0.28	17	17
YWHAQ	0.026	0.003	-10000	0	-10000	0	0
TBC1D4	0.005	0.016	-10000	0	-0.25	2	2
MAP3K5	0.02	0.049	-10000	0	-0.43	6	6
MAPKAP1	0.025	0.005	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.024	0.068	0.46	2	-0.19	7	9
YWHAH	0.019	0.033	-10000	0	-10000	0	0
AKT1S1	0.016	0.037	-10000	0	-0.28	4	4
CASP9	0.011	0.05	-10000	0	-0.28	11	11
YWHAB	0.025	0.005	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.033	0.065	0.24	2	-0.27	15	17
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.048	0.024	-10000	0	-0.26	2	2
YWHAE	0.026	0.002	-10000	0	-10000	0	0
SRC	0.025	0.005	-10000	0	-10000	0	0
AKT2/p21CIP1	0.001	0.061	-10000	0	-0.26	8	8
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.01	0.018	-10000	0	-10000	0	0
CHUK	0.01	0.056	-10000	0	-0.28	15	15
BAD/BCL-XL	0.032	0.061	-10000	0	-0.27	17	17
mTORC2	0.032	0.007	-10000	0	-10000	0	0
AKT2	0.011	0.02	-10000	0	-0.29	2	2
FOXO1-3a-4/14-3-3 family	0.023	0.08	0.23	1	-0.48	2	3
PDPK1	0.024	0.028	-10000	0	-0.43	2	2
MDM2	0.013	0.061	0.26	1	-0.28	16	17
MAPKKK cascade	-0.032	0.059	0.28	15	-10000	0	15
MDM2/Cbp/p300	0.043	0.064	0.26	1	-0.27	13	14
TSC1/TSC2	0.014	0.068	0.24	15	-0.28	17	32
proteasomal ubiquitin-dependent protein catabolic process	0.041	0.062	0.25	1	-0.26	13	14
glucose import	-0.016	0.064	0.21	2	-0.24	35	37
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.022	0.047	0.2	14	-10000	0	14
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.012	0.051	-10000	0	-0.22	27	27
GSK3A	0.017	0.041	-10000	0	-0.28	5	5
FOXO1	0.011	0.059	-10000	0	-0.28	16	16
GSK3B	0.011	0.057	-10000	0	-0.28	16	16
SFN	-0.023	0.11	-10000	0	-0.22	90	90
G1/S transition of mitotic cell cycle	0.02	0.051	0.26	10	-0.28	4	14
p27Kip1/14-3-3 family	0.024	0.066	-10000	0	-0.93	1	1
PRKACA	0.025	0.005	-10000	0	-10000	0	0
KPNA1	0.026	0.004	-10000	0	-10000	0	0
HSP90AA1	0.025	0.005	-10000	0	-10000	0	0
YWHAG	0.019	0.024	-10000	0	-0.13	11	11
RHEB	0.02	0.011	-10000	0	-10000	0	0
CREBBP	0.026	0.003	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	0.016	0.12	-9999	-0.28	70	70
Ran/GTP/Exportin 1/HDAC1	0.006	0.005	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.001	0.12	-9999	-0.28	65	65
SUMO1	0.026	0.002	-9999	-10000	0	0
ZFPM1	0.025	0.02	-9999	-0.43	1	1
NPC/RanGAP1/SUMO1/Ubc9	0.015	0.003	-9999	-10000	0	0
FKBP3	0.026	0.004	-9999	-10000	0	0
Histones	0.026	0.075	-9999	-0.33	1	1
YY1/LSF	0.027	0.04	-9999	-0.25	5	5
SMG5	0.025	0.005	-9999	-10000	0	0
RAN	0.026	0.003	-9999	-10000	0	0
I kappa B alpha/HDAC3	-0.016	0.087	-9999	-0.23	67	67
I kappa B alpha/HDAC1	0.009	0.073	-9999	-0.31	9	9
SAP18	0.025	0.005	-9999	-10000	0	0
RELA	-0.006	0.083	-9999	-0.21	64	64
HDAC1/Smad7	0.034	0.026	-9999	-10000	0	0
RANGAP1	0.026	0.004	-9999	-10000	0	0
HDAC3/TR2	0.01	0.071	-9999	-0.27	4	4
NuRD/MBD3 Complex	0.019	0.023	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.008	0.088	-9999	-0.29	9	9
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	0.015	0.065	-9999	-0.43	10	10
GATA1	0.013	0.025	-9999	-0.13	7	7
Mad/Max	0.037	0.008	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.015	0.066	-9999	-0.36	1	1
RBBP7	0.026	0.003	-9999	-10000	0	0
NPC	0.016	0.001	-9999	-10000	0	0
RBBP4	0.021	0.022	-9999	-0.43	1	1
MAX	0.025	0.005	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.026	0.004	-9999	-10000	0	0
NFKBIA	-0.013	0.075	-9999	-0.19	68	68
KAT2B	0.025	0.008	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.021	0.017	-9999	-10000	0	0
SIN3 complex	0.059	0.023	-9999	-10000	0	0
SMURF1	0.021	0.011	-9999	-10000	0	0
CHD3	0.025	0.02	-9999	-0.43	1	1
SAP30	0.025	0.005	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.024	0.028	-9999	-0.43	2	2
YY1/HDAC3	0.002	0.062	-9999	-0.29	2	2
YY1/HDAC2	0.028	0.036	-9999	-0.21	5	5
YY1/HDAC1	0.022	0.038	-9999	-0.21	7	7
NuRD/MBD2 Complex (MeCP1)	0.019	0.029	-9999	-0.34	1	1
PPARG	-0.026	0.12	-9999	-0.29	78	78
HDAC8/hEST1B	0.049	0.016	-9999	-10000	0	0
UBE2I	0.026	0.002	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.026	0.004	-9999	-10000	0	0
TNFRSF1A	0.017	0.054	-9999	-0.34	10	10
HDAC3/SMRT (N-CoR2)	0.01	0.071	-9999	-0.27	4	4
MBD3L2	-0.015	0.005	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.034	0.026	-9999	-10000	0	0
CREBBP	0.026	0.003	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.014	0.063	-9999	-10000	0	0
HDAC1	0.022	0.01	-9999	-10000	0	0
HDAC3	-0.01	0.064	-9999	-0.26	3	3
HDAC2	0.025	0.005	-9999	-10000	0	0
YY1	0.017	0.024	-9999	-0.24	4	4
HDAC8	0.026	0.003	-9999	-10000	0	0
SMAD7	0.026	0.004	-9999	-10000	0	0
NCOR2	0.026	0.003	-9999	-10000	0	0
MXD1	0.026	0.002	-9999	-10000	0	0
STAT3	0.019	0.027	-9999	-0.28	4	4
NFKB1	0.026	0.004	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.026	0.002	-9999	-10000	0	0
YY1/LSF/HDAC1	0.034	0.042	-9999	-0.24	4	4
YY1/SAP30/HDAC1	0.034	0.039	-9999	-0.19	7	7
EP300	0.022	0.04	-9999	-0.43	4	4
STAT3 (dimer non-phopshorylated)	0.018	0.027	-9999	-0.28	4	4
proteasomal ubiquitin-dependent protein catabolic process	-0.013	0.075	-9999	-0.19	68	68
histone deacetylation	0.031	0.037	-9999	-0.33	1	1
STAT3 (dimer non-phopshorylated)/HDAC3	0.005	0.061	-9999	-0.23	7	7
nuclear export	-0.048	0.015	-9999	-10000	0	0
PRKACA	0.025	0.005	-9999	-10000	0	0
GATAD2B	0.026	0.004	-9999	-10000	0	0
GATAD2A	0.025	0.005	-9999	-10000	0	0
GATA2/HDAC3	0.006	0.08	-9999	-0.26	14	14
GATA1/HDAC1	0.029	0.02	-9999	-10000	0	0
GATA1/HDAC3	0.007	0.072	-9999	-0.25	6	6
CHD4	0.025	0.007	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.031	0.12	-9999	-0.32	69	69
SIN3/HDAC complex/Mad/Max	0.017	0.034	-9999	-10000	0	0
NuRD Complex	0.016	0.066	-9999	-0.25	1	1
positive regulation of chromatin silencing	0.025	0.073	-9999	-0.33	1	1
SIN3B	0.025	0.006	-9999	-10000	0	0
MTA2	0.025	0.005	-9999	-10000	0	0
SIN3A	0.026	0.003	-9999	-10000	0	0
XPO1	0.026	0.002	-9999	-10000	0	0
SUMO1/HDAC1	0.034	0.024	-9999	-0.23	1	1
HDAC complex	0.053	0.031	-9999	-0.24	1	1
GATA1/Fog1	0.034	0.022	-9999	-0.31	1	1
FKBP25/HDAC1/HDAC2	0.042	0.023	-9999	-10000	0	0
TNF	-0.06	0.16	-9999	-0.26	151	151
negative regulation of cell growth	0.02	0.047	-9999	-0.24	6	6
NuRD/MBD2/PRMT5 Complex	0.019	0.029	-9999	-0.34	1	1
Ran/GTP/Exportin 1	0.043	0.019	-9999	-0.21	1	1
NF kappa B/RelA/I kappa B alpha	-0.019	0.11	-9999	-0.29	69	69
SIN3/HDAC complex/NCoR1	0.021	0.047	-9999	-0.25	9	9
TFCP2	0.025	0.02	-9999	-0.43	1	1
NR2C1	0.026	0.003	-9999	-10000	0	0
MBD3	0.025	0.006	-9999	-10000	0	0
MBD2	0.026	0.004	-9999	-10000	0	0

×

Canonical NF-kappaB pathway

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
FBXW11	0.028	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.053	0.06	0.21	9	-0.28	1	10
ERC1	0.024	0.007	-10000	0	-10000	0	0
RIP2/NOD2	0.026	0.051	-10000	0	-0.3	9	9
NFKBIA	0.019	0.034	0.21	15	-10000	0	15
BIRC2	0.025	0.005	-10000	0	-10000	0	0
IKBKB	0.025	0.005	-10000	0	-10000	0	0
RIPK2	0.024	0.007	-10000	0	-10000	0	0
IKBKG	0.02	0.033	-10000	0	-10000	0	0
IKK complex/A20	0.03	0.099	-10000	0	-0.36	5	5
NEMO/A20/RIP2	0.024	0.007	-10000	0	-10000	0	0
XPO1	0.026	0.002	-10000	0	-10000	0	0
NEMO/ATM	0.038	0.044	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.026	0.003	-10000	0	-10000	0	0
Exportin 1/RanGTP	0.035	0.005	-10000	0	-10000	0	0
IKK complex/ELKS	0.045	0.045	-10000	0	-10000	0	0
BCL10/MALT1/TRAF6	0.041	0.025	-10000	0	-0.23	1	1
NOD2	0.011	0.069	-10000	0	-0.43	10	10
NFKB1	0.028	0.004	-10000	0	-10000	0	0
RELA	0.027	0.005	-10000	0	-10000	0	0
MALT1	0.026	0.004	-10000	0	-10000	0	0
cIAP1/UbcH5C	0.037	0.01	-10000	0	-10000	0	0
ATM	0.025	0.005	-10000	0	-10000	0	0
TNF/TNFR1A	-0.031	0.12	-10000	0	-0.32	69	69
TRAF6	0.024	0.021	-10000	0	-0.43	1	1
PRKCA	0.024	0.021	-10000	0	-0.43	1	1
CHUK	0.025	0.005	-10000	0	-10000	0	0
UBE2D3	0.026	0.004	-10000	0	-10000	0	0
TNF	-0.06	0.16	-10000	0	-0.26	151	151
NF kappa B1 p50/RelA	0.056	0.016	-10000	0	-10000	0	0
BCL10	0.021	0.01	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.019	0.034	0.21	15	-10000	0	15
beta TrCP1/SCF ubiquitin ligase complex	0.028	0.004	-10000	0	-10000	0	0
TNFRSF1A	0.017	0.054	-10000	0	-0.34	10	10
IKK complex	0.053	0.05	0.25	1	-10000	0	1
CYLD	0.026	0.003	-10000	0	-10000	0	0
IKK complex/PKC alpha	0.059	0.054	-10000	0	-0.36	1	1

×

HIF-2-alpha transcription factor network

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
MMP14	-0.005	0.21	-10000	0	-0.94	22	22
oxygen homeostasis	0.002	0.01	-10000	0	-10000	0	0
TCEB2	0.026	0.003	-10000	0	-10000	0	0
TCEB1	0.025	0.006	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	0.035	0.09	-10000	0	-0.32	5	5
EPO	0.027	0.13	-10000	0	-0.52	5	5
FIH (dimer)	0.022	0.021	-10000	0	-10000	0	0
APEX1	0.022	0.024	-10000	0	-10000	0	0
SERPINE1	-0.011	0.19	-10000	0	-0.45	64	64
FLT1	0.013	0.14	-10000	0	-0.65	16	16
ADORA2A	0.017	0.15	0.34	3	-0.47	9	12
germ cell development	0.016	0.16	-10000	0	-0.48	19	19
SLC11A2	0.023	0.15	-10000	0	-0.52	6	6
BHLHE40	0.018	0.16	-10000	0	-0.55	13	13
HIF1AN	0.022	0.021	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	0.036	0.12	-10000	0	-0.37	7	7
ETS1	0.026	0.054	-10000	0	-0.31	10	10
CITED2	0.017	0.12	-10000	0	-0.66	9	9
KDR	0.016	0.14	-10000	0	-0.73	16	16
PGK1	0.023	0.15	-10000	0	-0.52	6	6
SIRT1	0.025	0.005	-10000	0	-10000	0	0
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	0.059	0.18	-10000	0	-0.53	10	10
EPAS1	0.012	0.073	-10000	0	-0.31	7	7
SP1	0.025	0.024	-10000	0	-0.12	1	1
ABCG2	0.022	0.16	-10000	0	-0.6	6	6
EFNA1	0.023	0.15	-10000	0	-0.5	8	8
FXN	0.018	0.14	0.34	3	-0.52	5	8
POU5F1	0.015	0.17	-10000	0	-0.49	19	19
neuron apoptosis	-0.058	0.18	0.52	10	-10000	0	10
EP300	0.022	0.04	-10000	0	-0.43	4	4
EGLN3	0.012	0.069	-10000	0	-0.43	11	11
EGLN2	0.018	0.022	-10000	0	-10000	0	0
EGLN1	0.022	0.021	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.049	0.015	-10000	0	-10000	0	0
VHL	0.026	0.004	-10000	0	-10000	0	0
ARNT	0.021	0.025	-10000	0	-10000	0	0
SLC2A1	0.015	0.14	0.35	2	-0.5	7	9
TWIST1	0.011	0.15	0.34	2	-0.5	14	16
ELK1	0.031	0.005	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.042	0.12	-10000	0	-0.39	5	5
VEGFA	0.022	0.15	-10000	0	-0.5	7	7
CREBBP	0.026	0.003	-10000	0	-10000	0	0

×

FoxO family signaling

Figure S114. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S114. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	-0.002	0.14	-10000	0	-1.3	5	5
PLK1	0.024	0.16	-10000	0	-1.3	5	5
CDKN1B	0.052	0.11	-10000	0	-0.34	7	7
FOXO3	0.042	0.098	-10000	0	-0.52	5	5
KAT2B	0.03	0.014	-10000	0	-10000	0	0
FOXO1/SIRT1	0.019	0.076	-10000	0	-0.57	5	5
CAT	0.036	0.12	-10000	0	-1.2	1	1
CTNNB1	0.026	0.004	-10000	0	-10000	0	0
AKT1	0.031	0.016	-10000	0	-10000	0	0
FOXO1	0.008	0.08	-10000	0	-0.62	5	5
MAPK10	0.044	0.061	0.19	68	-0.21	2	70
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
FOXO4	0.06	0.065	0.29	2	-0.36	1	3
response to oxidative stress	0.008	0.01	-10000	0	-0.087	1	1
FOXO3A/SIRT1	0.044	0.1	-10000	0	-0.49	5	5
XPO1	0.027	0.002	-10000	0	-10000	0	0
EP300	0.023	0.041	-10000	0	-0.43	4	4
BCL2L11	0.024	0.12	-10000	0	-1.3	4	4
FOXO1/SKP2	0.018	0.082	-10000	0	-0.48	8	8
mol:GDP	0.008	0.01	-10000	0	-0.087	1	1
RAN	0.027	0.003	-10000	0	-10000	0	0
GADD45A	-0.033	0.22	-10000	0	-0.55	28	28
YWHAQ	0.026	0.003	-10000	0	-10000	0	0
FOXO1/14-3-3 family	0.035	0.071	-10000	0	-0.57	2	2
MST1	0.006	0.1	-10000	0	-0.36	32	32
CSNK1D	0.025	0.005	-10000	0	-10000	0	0
CSNK1E	0.026	0.004	-10000	0	-10000	0	0
FOXO4/14-3-3 family	-0.001	0.094	-10000	0	-0.66	2	2
YWHAB	0.025	0.005	-10000	0	-10000	0	0
MAPK8	0.035	0.064	0.19	54	-0.22	11	65
MAPK9	0.046	0.059	0.19	71	-10000	0	71
YWHAG	0.019	0.024	-10000	0	-0.13	11	11
YWHAE	0.026	0.002	-10000	0	-10000	0	0
YWHAZ	0.023	0.008	-10000	0	-10000	0	0
SIRT1	0.024	0.007	-10000	0	-10000	0	0
SOD2	0.054	0.1	-10000	0	-0.68	2	2
RBL2	0.057	0.095	-10000	0	-1.1	1	1
RAL/GDP	0.037	0.018	-10000	0	-10000	0	0
CHUK	0.03	0.013	-10000	0	-10000	0	0
Ran/GTP	0.022	0.004	-10000	0	-10000	0	0
CSNK1G2	0.025	0.006	-10000	0	-10000	0	0
RAL/GTP	0.04	0.019	-10000	0	-10000	0	0
CSNK1G1	0.026	0.008	-10000	0	-0.13	1	1
FASLG	0.025	0.023	-10000	0	-10000	0	0
SKP2	0.021	0.046	-10000	0	-0.43	5	5
USP7	0.027	0.002	-10000	0	-10000	0	0
IKBKB	0.03	0.013	-10000	0	-10000	0	0
CCNB1	0.032	0.1	-10000	0	-10000	0	0
FOXO1-3a-4/beta catenin	0.079	0.091	-10000	0	-0.39	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.018	0.081	-10000	0	-0.47	8	8
CSNK1A1	0.026	0.003	-10000	0	-10000	0	0
SGK1	0.019	0.07	-10000	0	-0.42	12	12
CSNK1G3	0.026	0.003	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.039	0.006	-10000	0	-10000	0	0
ZFAND5	0.059	0.064	0.35	3	-10000	0	3
SFN	-0.023	0.11	-10000	0	-0.22	90	90
CDK2	0.02	0.046	-10000	0	-0.43	4	4
FOXO3A/14-3-3	0.008	0.086	-10000	0	-0.68	2	2
CREBBP	0.026	0.014	-10000	0	-0.13	1	1
FBXO32	0.051	0.15	-10000	0	-1.2	3	3
BCL6	0.052	0.11	-10000	0	-0.72	4	4
RALB	0.027	0.002	-10000	0	-10000	0	0
RALA	0.023	0.009	-10000	0	-10000	0	0
YWHAH	0.019	0.033	-10000	0	-10000	0	0

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.026	0.002	-10000	0	-10000	0	0
PTK2	0.023	0.008	-10000	0	-10000	0	0
CRKL	0.01	0.037	0.16	2	-0.22	11	13
GRB2/SOS1/SHC	0.05	0.014	-10000	0	-10000	0	0
HRAS	0.025	0.006	-10000	0	-10000	0	0
IRS1/Crk	0.02	0.039	-10000	0	-0.22	12	12
IGF-1R heterotetramer/IGF1/PTP1B	0.042	0.046	-10000	0	-0.24	12	12
AKT1	-0.009	0.041	0.17	7	-0.2	10	17
BAD	-0.009	0.038	0.16	7	-0.22	1	8
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.01	0.038	0.16	2	-0.22	12	14
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.027	0.041	0.2	1	-0.22	12	13
RAF1	0.008	0.059	-10000	0	-0.42	5	5
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.052	0.045	-10000	0	-0.21	11	11
YWHAZ	0.023	0.008	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.028	0.043	-10000	0	-0.24	12	12
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
RPS6KB1	-0.008	0.043	0.19	7	-0.2	12	19
GNB2L1	0.026	0.004	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	0.002	0.049	-10000	0	-0.34	4	4
PXN	0.026	0.004	-10000	0	-10000	0	0
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.037	0.009	-10000	0	-10000	0	0
HRAS/GTP	0.025	0.034	-10000	0	-0.2	9	9
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.064	0.047	-10000	0	-0.19	12	12
IGF-1R heterotetramer	0.025	0.016	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	0.042	0.044	-10000	0	-0.22	12	12
Crk/p130 Cas/Paxillin	0.051	0.046	0.21	2	-0.2	13	15
IGF1R	0.025	0.016	-10000	0	-10000	0	0
IGF1	0.014	0.077	-10000	0	-0.36	19	19
IRS2/Crk	0.019	0.039	0.16	2	-0.21	13	15
PI3K	0.054	0.045	-10000	0	-0.21	12	12
apoptosis	-0.014	0.04	-10000	0	-10000	0	0
HRAS/GDP	0.018	0.005	-10000	0	-10000	0	0
PRKCD	-0.001	0.086	-10000	0	-0.42	16	16
RAF1/14-3-3 E	0.025	0.058	-10000	0	-0.37	5	5
BAD/14-3-3	0.015	0.041	-10000	0	-10000	0	0
PRKCZ	-0.013	0.05	0.17	6	-0.21	17	23
Crk/p130 Cas/Paxillin/FAK1	0.028	0.041	-10000	0	-0.21	1	1
PTPN1	0.025	0.005	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.012	0.062	-10000	0	-0.34	15	15
BCAR1	0.025	0.02	-10000	0	-0.43	1	1
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.046	0.051	-10000	0	-0.21	14	14
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.026	0.002	-10000	0	-10000	0	0
IRS1/NCK2	0.027	0.042	-10000	0	-0.22	12	12
GRB10	0.021	0.03	-10000	0	-0.43	2	2
PTPN11	0.01	0.038	0.16	2	-0.22	12	14
IRS1	0.012	0.043	0.12	11	-0.24	12	23
IRS2	0.009	0.039	0.16	2	-0.22	13	15
IGF-1R heterotetramer/IGF1	0.027	0.058	-10000	0	-0.32	13	13
GRB2	0.025	0.006	-10000	0	-10000	0	0
PDPK1	0.012	0.045	0.19	8	-0.2	13	21
YWHAE	0.026	0.002	-10000	0	-10000	0	0
PRKD1	0.008	0.06	-10000	0	-0.32	15	15
SHC1	0.024	0.014	-10000	0	-10000	0	0

×

S1P3 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.025	0.013	-10000	0	-10000	0	0
mol:S1P	0.001	0.004	-10000	0	-10000	0	0
S1P1/S1P/Gi	0.013	0.039	-10000	0	-0.25	8	8
GNAO1	0.022	0.046	-10000	0	-0.44	5	5
S1P/S1P3/G12/G13	0.038	0.043	-10000	0	-0.23	9	9
AKT1	0.015	0.074	-10000	0	-0.38	14	14
AKT3	0.013	0.13	-10000	0	-1	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.025	0.013	-10000	0	-10000	0	0
GNAI2	0.026	0.008	-10000	0	-10000	0	0
GNAI3	0.022	0.012	-10000	0	-10000	0	0
GNAI1	0.02	0.036	-10000	0	-0.43	3	3
mol:GDP	0	0	-10000	0	-10000	0	0
S1PR3	0.006	0.075	-10000	0	-0.43	11	11
S1PR2	0.022	0.036	-10000	0	-0.43	3	3
EDG1	0	0	-10000	0	-10000	0	0
mol:Ca2+	0.011	0.074	-10000	0	-0.27	19	19
MAPK3	0.006	0.07	-10000	0	-0.28	15	15
MAPK1	0.008	0.065	-10000	0	-0.26	14	14
JAK2	0.008	0.076	0.2	3	-0.3	13	16
CXCR4	0.001	0.078	-10000	0	-0.28	20	20
FLT1	0.026	0.024	-10000	0	-0.49	1	1
RhoA/GDP	0.019	0.003	-10000	0	-10000	0	0
Rac1/GDP	0.017	0.007	-10000	0	-10000	0	0
SRC	0.005	0.066	-10000	0	-0.29	13	13
S1P/S1P3/Gi	0.011	0.075	-10000	0	-0.27	19	19
RAC1	0.023	0.009	-10000	0	-10000	0	0
RhoA/GTP	0.019	0.073	-10000	0	-0.27	15	15
VEGFA	0.021	0.033	-10000	0	-0.13	22	22
S1P/S1P2/Gi	0.014	0.062	-10000	0	-0.27	9	9
VEGFR1 homodimer/VEGFA homodimer	0.036	0.034	-10000	0	-0.4	1	1
RHOA	0.026	0.004	-10000	0	-10000	0	0
S1P/S1P3/Gq	0.002	0.08	-10000	0	-0.25	41	41
GNAQ	0.026	0.004	-10000	0	-10000	0	0
GNAZ	0.026	0.008	-10000	0	-10000	0	0
G12/G13	0.032	0.015	-10000	0	-10000	0	0
GNA14	0.009	0.081	-10000	0	-0.34	23	23
GNA15	0.013	0.07	-10000	0	-0.43	12	12
GNA12	0.022	0.009	-10000	0	-10000	0	0
GNA13	0.025	0.005	-10000	0	-10000	0	0
GNA11	0.017	0.06	-10000	0	-0.43	9	9
Rac1/GTP	0.012	0.068	-10000	0	-0.28	13	13

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.029	0.13	-10000	0	-0.43	46	46
oxygen homeostasis	0	0	-10000	0	-10000	0	0
TCEB2	0.026	0.003	-10000	0	-10000	0	0
TCEB1	0.025	0.006	-10000	0	-10000	0	0
HIF1A/p53	0.014	0.058	-10000	0	-0.26	8	8
HIF1A	0.009	0.034	-10000	0	-0.25	6	6
COPS5	0.025	0.006	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.065	0.03	-10000	0	-10000	0	0
FIH (dimer)	0.025	0.005	-10000	0	-10000	0	0
CDKN2A	-0.013	0.11	-10000	0	-0.3	55	55
ARNT/IPAS	-0.006	0.096	-10000	0	-0.3	43	43
HIF1AN	0.025	0.005	-10000	0	-10000	0	0
GNB2L1	0.026	0.004	-10000	0	-10000	0	0
HIF1A/ARNT	0.018	0.047	-10000	0	-0.27	7	7
CUL2	0.024	0.007	-10000	0	-10000	0	0
OS9	0.025	0.006	-10000	0	-10000	0	0
RACK1/Elongin B/Elongin C	0.049	0.015	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF1A/Hsp90	0.021	0.047	-10000	0	-0.26	8	8
PHD1-3/OS9	0.047	0.046	-10000	0	-0.22	9	9
HIF1A/RACK1/Elongin B/Elongin C	0.04	0.051	0.29	1	-0.26	6	7
VHL	0.026	0.004	-10000	0	-10000	0	0
HSP90AA1	0.025	0.005	-10000	0	-10000	0	0
HIF1A/JAB1	0.019	0.047	-10000	0	-0.27	6	6
EGLN3	0.016	0.066	-10000	0	-0.43	11	11
EGLN2	0.022	0.01	-10000	0	-10000	0	0
EGLN1	0.026	0.004	-10000	0	-10000	0	0
TP53	0.014	0.072	-10000	0	-0.41	14	14
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.031	0.065	-10000	0	-0.53	6	6
ARNT	0.025	0.008	-10000	0	-10000	0	0
ARD1A	0	0	-10000	0	-10000	0	0
RBX1	0.026	0.004	-10000	0	-10000	0	0
HIF1A/p19ARF	0.006	0.069	0.31	1	-0.28	8	9

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	0.018	0.063	-10000	0	-0.3	12	12
AKT1	0.034	0.078	0.32	5	-0.52	4	9
PTK2B	0.005	0.073	0.35	2	-0.45	4	6
VEGFR2 homodimer/Frs2	0.028	0.052	-10000	0	-0.61	3	3
CAV1	0.006	0.051	-10000	0	-0.43	2	2
CALM1	0.025	0.009	-10000	0	-0.13	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.044	0.053	-10000	0	-0.57	3	3
endothelial cell proliferation	0.043	0.084	0.28	17	-0.45	4	21
mol:Ca2+	0.019	0.06	0.36	1	-0.38	5	6
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.047	0.061	-10000	0	-0.36	7	7
RP11-342D11.1	0.008	0.058	0.18	2	-0.41	5	7
CDH5	0.025	0.012	-10000	0	-10000	0	0
VEGFA homodimer	0.063	0.024	-10000	0	-0.23	1	1
SHC1	0.024	0.014	-10000	0	-10000	0	0
SHC2	0.025	0.006	-10000	0	-10000	0	0
HRAS/GDP	0.038	0.049	-10000	0	-0.42	3	3
SH2D2A	-0.02	0.12	-10000	0	-0.27	77	77
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.059	0.081	0.28	5	-0.41	6	11
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.023	0.089	-10000	0	-0.26	37	37
VEGFR1 homodimer	0.024	0.021	-10000	0	-0.43	1	1
SHC/GRB2/SOS1	0.065	0.058	-10000	0	-0.37	5	5
GRB10	0.015	0.066	0.36	1	-0.52	5	6
PTPN11	0.026	0.003	-10000	0	-10000	0	0
GRB2	0.025	0.006	-10000	0	-10000	0	0
PAK1	0.008	0.061	-10000	0	-0.43	5	5
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.063	0.062	-10000	0	-0.53	3	3
HRAS	0.025	0.006	-10000	0	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	0.019	0.052	-10000	0	-0.36	5	5
HIF1A	0.025	0.021	-10000	0	-0.43	1	1
FRS2	0.026	0.004	-10000	0	-10000	0	0
oxygen and reactive oxygen species metabolic process	0.046	0.06	-10000	0	-0.35	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.021	0.039	-10000	0	-0.43	3	3
Nck/Pak	0.023	0.05	-10000	0	-0.3	6	6
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.044	0.053	-10000	0	-0.57	3	3
mol:GDP	0.051	0.054	-10000	0	-0.36	5	5
mol:NADP	0.042	0.071	0.27	6	-0.37	6	12
eNOS/Hsp90	0.053	0.068	0.28	5	-0.36	5	10
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
mol:IP3	0.019	0.06	0.36	1	-0.38	5	6
HIF1A/ARNT	0.036	0.018	-10000	0	-0.3	1	1
SHB	0.026	0.004	-10000	0	-10000	0	0
VEGFA	0.02	0.033	-10000	0	-10000	0	0
VEGFC	0.017	0.051	-10000	0	-0.21	18	18
FAK1/Vinculin	0.038	0.082	0.3	2	-0.53	5	7
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.026	0.004	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.048	0.072	-10000	0	-0.28	14	14
PTPN6	0.014	0.064	-10000	0	-0.43	10	10
EPAS1	0.03	0.029	-10000	0	-0.33	3	3
mol:L-citrulline	0.042	0.071	0.27	6	-0.37	6	12
ITGAV	0.026	0.002	-10000	0	-10000	0	0
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.055	0.051	-10000	0	-0.49	3	3
VEGFR2 homodimer/VEGFA homodimer	0.047	0.06	-10000	0	-0.36	8	8
VEGFR2/3 heterodimer	0.026	0.058	-10000	0	-0.47	5	5
VEGFB	0.025	0.005	-10000	0	-10000	0	0
MAPK11	0.004	0.072	0.32	5	-0.52	4	9
VEGFR2 homodimer	0.015	0.056	-10000	0	-0.69	3	3
FLT1	0.024	0.021	-10000	0	-0.43	1	1
NEDD4	0.022	0.04	-10000	0	-0.22	10	10
MAPK3	0.004	0.064	0.28	4	-0.38	4	8
MAPK1	0.005	0.064	0.27	5	-0.38	4	9
VEGFA145/NRP2	0.03	0.043	-10000	0	-0.28	6	6
VEGFR1/2 heterodimer	0.028	0.052	-10000	0	-0.61	3	3
KDR	0.015	0.056	-10000	0	-0.7	3	3
VEGFA165/NRP1/VEGFR2 homodimer	0.043	0.062	-10000	0	-0.41	5	5
SRC	0.025	0.005	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	0.006	0.068	0.28	5	-0.4	4	9
PI3K	0.041	0.063	-10000	0	-0.54	3	3
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.045	0.053	-10000	0	-0.57	3	3
FES	0.017	0.062	-10000	0	-0.42	5	5
GAB1	0.028	0.059	-10000	0	-0.5	4	4
VEGFR2 homodimer/VEGFA homodimer/Src	0.043	0.05	-10000	0	-0.51	3	3
CTNNB1	0.026	0.004	-10000	0	-10000	0	0
SOS1	0.026	0.002	-10000	0	-10000	0	0
ARNT	0.025	0.008	-10000	0	-10000	0	0
eNOS/Caveolin-1	0.032	0.066	0.31	2	-0.39	5	7
VEGFR2 homodimer/VEGFA homodimer/Yes	0.042	0.055	-10000	0	-0.36	7	7
PI3K/GAB1	0.046	0.066	-10000	0	-0.47	4	4
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.063	0.063	-10000	0	-0.53	3	3
PRKACA	0.025	0.005	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.037	0.063	-10000	0	-0.34	10	10
HSP90AA1	0.025	0.005	-10000	0	-10000	0	0
CDC42	0.015	0.062	0.36	1	-0.42	5	6
actin cytoskeleton reorganization	0.023	0.089	-10000	0	-0.25	37	37
PTK2	0.016	0.065	-10000	0	-0.57	3	3
EDG1	0.008	0.058	0.18	2	-0.41	5	7
mol:DAG	0.019	0.06	0.36	1	-0.38	5	6
CaM/Ca2+	0.028	0.055	-10000	0	-0.36	5	5
MAP2K3	0.005	0.069	0.36	1	-0.51	3	4
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.065	0.088	-10000	0	-0.53	5	5
PLCG1	0.019	0.061	0.36	1	-0.39	5	6
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.055	0.052	-10000	0	-0.49	3	3
IQGAP1	0.02	0.043	-10000	0	-0.25	10	10
YES1	0.022	0.04	-10000	0	-0.43	4	4
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.045	0.053	-10000	0	-0.57	3	3
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.037	0.065	-10000	0	-0.32	11	11
cell migration	0.046	0.09	0.32	3	-0.51	6	9
mol:PI-3-4-5-P3	0.04	0.06	-10000	0	-0.5	3	3
FYN	0.025	0.005	-10000	0	-10000	0	0
VEGFB/NRP1	0.022	0.058	-10000	0	-0.39	5	5
mol:NO	0.042	0.071	0.27	6	-0.37	6	12
PXN	0.026	0.004	-10000	0	-10000	0	0
HRAS/GTP	0.017	0.046	-10000	0	-0.42	3	3
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.033	0.066	-10000	0	-0.53	5	5
VHL	0.026	0.004	-10000	0	-10000	0	0
ITGB3	-0.001	0.082	-10000	0	-0.19	64	64
NOS3	0.043	0.075	0.3	3	-0.41	6	9
VEGFR2 homodimer/VEGFA homodimer/Sck	0.042	0.054	-10000	0	-0.57	3	3
RAC1	0.023	0.009	-10000	0	-10000	0	0
PRKCA	0.011	0.055	0.36	1	-0.39	3	4
PRKCB	-0.001	0.071	0.36	2	-0.3	12	14
VCL	0.022	0.032	-10000	0	-0.23	6	6
VEGFA165/NRP1	0.029	0.059	-10000	0	-0.41	5	5
VEGFR1/2 heterodimer/VEGFA homodimer	0.044	0.053	-10000	0	-0.57	3	3
VEGFA165/NRP2	0.03	0.043	-10000	0	-0.28	6	6
MAPKKK cascade	0.034	0.069	0.3	4	-0.42	5	9
NRP2	0.021	0.046	-10000	0	-0.32	8	8
VEGFC homodimer	0.017	0.051	-10000	0	-0.21	18	18
NCK1	0.025	0.02	-10000	0	-0.43	1	1
ROCK1	0.026	0.004	-10000	0	-10000	0	0
FAK1/Paxillin	0.041	0.08	0.29	3	-0.56	4	7
MAP3K13	0.014	0.072	0.36	1	-0.4	6	7
PDPK1	0.026	0.061	0.27	2	-0.5	3	5

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.019	0.13	-10000	0	-0.43	41	41
CLTC	0.024	0.054	-10000	0	-0.36	6	6
calcium ion-dependent exocytosis	0.012	0.05	-10000	0	-0.27	3	3
Dynamin 2/GTP	0.025	0.008	-10000	0	-10000	0	0
EXOC4	0.02	0.011	-10000	0	-10000	0	0
CD59	0.015	0.047	-10000	0	-0.31	8	8
CPE	0.007	0.041	-10000	0	-0.26	12	12
CTNNB1	0.026	0.004	-10000	0	-10000	0	0
membrane fusion	0.015	0.053	-10000	0	-0.15	32	32
CTNND1	0.014	0.024	0.18	10	-10000	0	10
DNM2	0.025	0.006	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.016	0.039	-10000	0	-0.25	2	2
TSHR	-0.05	0.1	-10000	0	-0.26	90	90
INS	-0.008	0.11	-10000	0	-0.45	27	27
BIN1	0.025	0.02	-10000	0	-0.43	1	1
mol:Choline	0.015	0.053	-10000	0	-0.15	32	32
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.014	0.003	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.026	0.004	-10000	0	-10000	0	0
mol:Ca2+	0.024	0.007	-10000	0	-10000	0	0
JUP	0.012	0.055	-10000	0	-0.31	10	10
ASAP2/amphiphysin II	0.048	0.016	-10000	0	-0.23	1	1
ARF6/GTP	0.019	0.003	-10000	0	-10000	0	0
CDH1	-0.008	0.079	-10000	0	-0.28	18	18
clathrin-independent pinocytosis	0.019	0.003	-10000	0	-10000	0	0
MAPK8IP3	0.026	0.002	-10000	0	-10000	0	0
positive regulation of endocytosis	0.019	0.003	-10000	0	-10000	0	0
EXOC2	0.026	0.004	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.019	0.022	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.026	0.004	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.016	0.071	0.3	7	-10000	0	7
positive regulation of phagocytosis	0.012	0.006	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.035	0.006	-10000	0	-10000	0	0
ACAP1	0.02	0.05	-10000	0	-0.23	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	-0.01	0.07	-10000	0	-0.31	11	11
clathrin heavy chain/ACAP1	0.026	0.058	0.2	18	-0.28	6	24
JIP4/KLC1	0.048	0.012	-10000	0	-10000	0	0
EXOC1	0.025	0.006	-10000	0	-10000	0	0
exocyst	0.02	0.02	-10000	0	-10000	0	0
RALA/GTP	0.017	0.007	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.034	0.007	-10000	0	-10000	0	0
receptor recycling	0.019	0.003	-10000	0	-10000	0	0
CTNNA1	0.014	0.023	0.18	9	-10000	0	9
NME1	0.014	0.003	-10000	0	-10000	0	0
clathrin coat assembly	0.026	0.057	0.25	2	-0.36	6	8
IL2RA	0.006	0.054	-10000	0	-0.31	9	9
VAMP3	0.012	0.006	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	0.017	0.07	-10000	0	-0.27	11	11
EXOC6	0.025	0.005	-10000	0	-10000	0	0
PLD1	-0.004	0.066	-10000	0	-0.26	31	31
PLD2	0.012	0.013	-10000	0	-0.25	1	1
EXOC5	0.026	0.004	-10000	0	-10000	0	0
PIP5K1C	0.016	0.037	-10000	0	-0.26	2	2
SDC1	0.011	0.053	-10000	0	-0.31	8	8
ARF6/GDP	0.024	0.005	-10000	0	-10000	0	0
EXOC7	0.025	0.005	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.018	0.073	-10000	0	-0.31	7	7
mol:Phosphatidic acid	0.015	0.053	-10000	0	-0.15	32	32
endocytosis	-0.047	0.015	0.23	1	-10000	0	1
SCAMP2	0.026	0.003	-10000	0	-10000	0	0
ADRB2	0.015	0.074	0.27	3	-0.35	8	11
EXOC3	0.026	0.005	-10000	0	-10000	0	0
ASAP2	0.026	0.003	-10000	0	-10000	0	0
Dynamin 2/GDP	0.028	0.009	-10000	0	-10000	0	0
KLC1	0.025	0.005	-10000	0	-10000	0	0
AVPR2	0.022	0.061	0.24	3	-0.34	7	10
RALA	0.023	0.009	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.019	0.073	-10000	0	-0.31	6	6

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	-0.02	0.045	0.38	6	-10000	0	6
PI3K Class IB/PDE3B	0.02	0.045	-10000	0	-0.38	6	6
PDE3B	0.02	0.045	-10000	0	-0.38	6	6

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.015	0.032	-10000	0	-0.21	8	8
TRAF2/ASK1	0.03	0.032	-10000	0	-0.26	6	6
ATM	0.025	0.005	-10000	0	-10000	0	0
MAP2K3	0.011	0.072	-10000	0	-0.39	4	4
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	-0.004	0.092	0.2	4	-0.32	15	19
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.002	0.09	-10000	0	-0.43	19	19
TXN	0.007	0.001	-10000	0	-10000	0	0
CALM1	0.025	0.009	-10000	0	-0.13	1	1
GADD45A	0.012	0.042	-10000	0	-0.43	1	1
GADD45B	0.01	0.067	-10000	0	-0.21	33	33
MAP3K1	0.024	0.019	-10000	0	-10000	0	0
MAP3K6	0.02	0.019	-10000	0	-10000	0	0
MAP3K7	0.026	0.004	-10000	0	-10000	0	0
MAP3K4	0.025	0.005	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.026	0.041	-10000	0	-0.3	6	6
TAK1/TAB family	-0.002	0.025	0.16	7	-0.13	5	12
RAC1/OSM/MEKK3	0.042	0.02	-10000	0	-10000	0	0
TRAF2	0.026	0.005	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.014	0.059	-10000	0	-0.32	3	3
TRAF6	0.006	0.013	-10000	0	-0.3	1	1
RAC1	0.023	0.009	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.018	0.12	-10000	0	-0.43	33	33
CCM2	0.022	0.009	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	0.003	0.073	-10000	0	-0.25	34	34
MAPK11	0.019	0.056	-10000	0	-0.43	8	8
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.021	0.08	-10000	0	-0.25	36	36
OSM/MEKK3	0.032	0.015	-10000	0	-10000	0	0
TAOK1	-0.012	0.085	-10000	0	-0.29	44	44
TAOK2	0.014	0.003	-10000	0	-10000	0	0
TAOK3	0.014	0.004	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.026	0.003	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.02	0.049	-10000	0	-0.43	6	6
MAP3K10	0.019	0.023	-10000	0	-10000	0	0
MAP3K3	0.025	0.005	-10000	0	-10000	0	0
TRX/ASK1	0.021	0.028	-10000	0	-0.2	7	7
GADD45/MTK1/MTK1	0.027	0.068	-10000	0	-0.22	24	24

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.037	0.05	-10000	0	-0.41	1	1
CLOCK	0.002	0.1	-10000	0	-0.43	28	28
TIMELESS/CRY2	0.026	0.047	-10000	0	-10000	0	0
DEC1/BMAL1	0.031	0.022	-10000	0	-10000	0	0
ATR	0.026	0.003	-10000	0	-10000	0	0
NR1D1	0.009	0.1	-10000	0	-1.3	3	3
ARNTL	0.025	0.015	-10000	0	-0.13	3	3
TIMELESS	0.013	0.041	-10000	0	-10000	0	0
NPAS2	0.021	0.052	-10000	0	-0.31	10	10
CRY2	0.023	0.035	-10000	0	-0.43	3	3
mol:CO	-0.007	0.011	0.13	3	-10000	0	3
CHEK1	0.023	0.018	-10000	0	-0.13	6	6
mol:HEME	0.007	0.011	-10000	0	-0.13	3	3
PER1	0.018	0.06	-10000	0	-0.43	9	9
BMAL/CLOCK/NPAS2	0.037	0.078	-10000	0	-0.25	33	33
BMAL1/CLOCK	0.005	0.11	-10000	0	-0.86	3	3
S phase of mitotic cell cycle	0.037	0.05	-10000	0	-0.41	1	1
TIMELESS/CHEK1/ATR	0.038	0.05	-10000	0	-0.42	1	1
mol:NADPH	0.007	0.011	-10000	0	-0.13	3	3
PER1/TIMELESS	0.025	0.054	-10000	0	-10000	0	0
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.008	0.029	-10000	0	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.022	0.01	-10000	0	-10000	0	0
HDAC2	0.025	0.005	-10000	0	-10000	0	0
GNB1/GNG2	0.031	0.038	-10000	0	-0.25	5	5
forebrain development	0.018	0.14	0.46	2	-0.46	23	25
GNAO1	0.022	0.045	-10000	0	-0.43	5	5
SMO/beta Arrestin2	0.029	0.031	-10000	0	-0.3	3	3
SMO	0.018	0.036	-10000	0	-0.43	3	3
ARRB2	0.026	0.004	-10000	0	-10000	0	0
GLI3/SPOP	0.016	0.087	0.22	1	-0.35	13	14
mol:GTP	0	0.001	-10000	0	-10000	0	0
GSK3B	0.025	0.02	-10000	0	-0.43	1	1
GNAI2	0.025	0.007	-10000	0	-10000	0	0
SIN3/HDAC complex	0.059	0.023	-10000	0	-10000	0	0
GNAI1	0.019	0.036	-10000	0	-0.43	3	3
XPO1	0.027	0.007	-10000	0	-10000	0	0
GLI1/Su(fu)	0.012	0.11	-10000	0	-0.76	5	5
SAP30	0.025	0.005	-10000	0	-10000	0	0
mol:GDP	0.018	0.036	-10000	0	-0.43	3	3
MIM/GLI2A	0.017	0.043	-10000	0	-0.37	5	5
IFT88	0.025	0.005	-10000	0	-10000	0	0
GNAI3	0.021	0.011	-10000	0	-10000	0	0
GLI2	0.031	0.048	0.27	2	-10000	0	2
GLI3	0.006	0.088	0.22	2	-0.36	14	16
CSNK1D	0.025	0.005	-10000	0	-10000	0	0
CSNK1E	0.026	0.004	-10000	0	-10000	0	0
SAP18	0.025	0.005	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.025	0.005	-10000	0	-10000	0	0
GNG2	0.022	0.04	-10000	0	-0.43	4	4
Gi family/GTP	0.002	0.055	-10000	0	-0.28	10	10
SIN3B	0.025	0.006	-10000	0	-10000	0	0
SIN3A	0.026	0.003	-10000	0	-10000	0	0
GLI3/Su(fu)	0.014	0.072	-10000	0	-0.44	5	5
GLI2/Su(fu)	0.027	0.049	-10000	0	-0.34	4	4
FOXA2	0.012	0.093	-10000	0	-0.75	5	5
neural tube patterning	0.018	0.14	0.46	2	-0.46	23	25
SPOP	0.026	0.004	-10000	0	-10000	0	0
Su(fu)/PIAS1	0.044	0.046	-10000	0	-0.22	4	4
GNB1	0.022	0.01	-10000	0	-10000	0	0
CSNK1G2	0.025	0.006	-10000	0	-10000	0	0
CSNK1G3	0.026	0.003	-10000	0	-10000	0	0
MTSS1	0.017	0.043	-10000	0	-0.37	5	5
embryonic limb morphogenesis	0.018	0.14	0.46	2	-0.46	23	25
SUFU	0.018	0.018	-10000	0	-10000	0	0
LGALS3	0.012	0.053	-10000	0	-0.16	39	39
catabolic process	0.042	0.09	0.29	1	-0.58	3	4
GLI3A/CBP	0.004	0.087	-10000	0	-0.32	31	31
KIF3A	0.025	0.02	-10000	0	-0.43	1	1
GLI1	0.018	0.14	0.46	2	-0.47	23	25
RAB23	0.025	0.02	-10000	0	-0.43	1	1
CSNK1A1	0.026	0.003	-10000	0	-10000	0	0
IFT172	0.023	0.035	-10000	0	-0.43	3	3
RBBP7	0.026	0.003	-10000	0	-10000	0	0
Su(fu)/Galectin3	0.045	0.047	-10000	0	-0.24	4	4
GNAZ	0.026	0.006	-10000	0	-10000	0	0
RBBP4	0.021	0.022	-10000	0	-0.43	1	1
CSNK1G1	0.026	0.008	-10000	0	-0.13	1	1
PIAS1	0.022	0.04	-10000	0	-0.43	4	4
PRKACA	0.025	0.005	-10000	0	-10000	0	0
GLI2/SPOP	0.04	0.051	-10000	0	-0.52	1	1
STK36	0.026	0.007	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.011	0.053	-10000	0	-0.37	6	6
PTCH1	0.015	0.16	0.57	1	-1.1	7	8
MIM/GLI1	0.022	0.14	0.55	1	-0.63	8	9
CREBBP	0.004	0.087	-10000	0	-0.32	31	31
Su(fu)/SIN3/HDAC complex	-0.006	0.11	0.24	2	-0.35	19	21

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.013	0.066	-10000	0	-0.97	2	2
regulation of axonogenesis	0.002	0.055	0.28	9	-10000	0	9
myoblast fusion	-0.008	0.041	0.35	4	-10000	0	4
mol:GTP	0.019	0.026	-10000	0	-0.16	7	7
regulation of calcium-dependent cell-cell adhesion	-0.043	0.027	0.2	2	-10000	0	2
ARF1/GTP	0.034	0.024	-10000	0	-0.15	2	2
mol:GM1	0.008	0.018	-10000	0	-0.15	2	2
mol:Choline	-0.009	0.065	-10000	0	-0.24	35	35
lamellipodium assembly	0.003	0.047	-10000	0	-0.37	6	6
MAPK3	0.02	0.026	-10000	0	-0.3	2	2
ARF6/GTP/NME1/Tiam1	0.044	0.027	-10000	0	-0.2	2	2
ARF1	0.026	0.004	-10000	0	-10000	0	0
ARF6/GDP	0.008	0.041	-10000	0	-0.35	4	4
ARF1/GDP	0.012	0.048	-10000	0	-0.28	7	7
ARF6	0.032	0.012	-10000	0	-0.14	1	1
RAB11A	0.026	0.003	-10000	0	-10000	0	0
TIAM1	0.025	0.007	-10000	0	-10000	0	0
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.02	0.026	-10000	0	-0.3	2	2
actin filament bundle formation	-0.016	0.047	0.27	7	-10000	0	7
KALRN	0.005	0.028	-10000	0	-0.25	4	4
RAB11FIP3/RAB11A	0.038	0.005	-10000	0	-10000	0	0
RhoA/GDP	0.017	0.047	-10000	0	-0.28	7	7
NME1	0.025	0.007	-10000	0	-10000	0	0
Rac1/GDP	0.015	0.045	-10000	0	-0.25	6	6
substrate adhesion-dependent cell spreading	0.019	0.026	-10000	0	-0.16	7	7
cortical actin cytoskeleton organization	0.003	0.048	-10000	0	-0.37	6	6
RAC1	0.023	0.009	-10000	0	-10000	0	0
liver development	0.019	0.026	-10000	0	-0.16	7	7
ARF6/GTP	0.019	0.026	-10000	0	-0.16	7	7
RhoA/GTP	0.035	0.023	-10000	0	-0.15	2	2
mol:GDP	0.008	0.032	-10000	0	-0.32	4	4
ARF6/GTP/RAB11FIP3/RAB11A	0.049	0.025	-10000	0	-10000	0	0
RHOA	0.026	0.004	-10000	0	-10000	0	0
PLD1	-0.004	0.075	-10000	0	-0.27	35	35
RAB11FIP3	0.026	0.002	-10000	0	-10000	0	0
tube morphogenesis	0.003	0.047	-10000	0	-0.37	6	6
ruffle organization	-0.002	0.055	-10000	0	-0.28	9	9
regulation of epithelial cell migration	0.019	0.026	-10000	0	-0.16	7	7
PLD2	0.016	0.026	-10000	0	-0.19	3	3
PIP5K1A	-0.002	0.055	-10000	0	-0.28	9	9
mol:Phosphatidic acid	-0.009	0.065	-10000	0	-0.24	35	35
Rac1/GTP	0.003	0.048	-10000	0	-0.37	6	6

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	0.052	0.037	-9999	-0.22	4	4
HDAC3	0.026	0.004	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0.007	0.002	-9999	-10000	0	0
GATA1/HDAC4	0.034	0.016	-9999	-10000	0	0
GATA1/HDAC5	0.035	0.016	-9999	-10000	0	0
GATA2/HDAC5	0.03	0.049	-9999	-0.3	10	10
HDAC5/BCL6/BCoR	0.052	0.01	-9999	-10000	0	0
HDAC9	0.015	0.055	-9999	-0.3	12	12
Glucocorticoid receptor/Hsp90/HDAC6	0.05	0.013	-9999	-10000	0	0
HDAC4/ANKRA2	0.037	0.009	-9999	-10000	0	0
HDAC5/YWHAB	0.037	0.008	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.015	0.003	-9999	-10000	0	0
GATA2	0.015	0.065	-9999	-0.43	10	10
HDAC4/RFXANK	0.036	0.011	-9999	-10000	0	0
BCOR	0.026	0.003	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.026	0.004	-9999	-10000	0	0
HDAC5	0.026	0.003	-9999	-10000	0	0
GNB1/GNG2	0.03	0.033	-9999	-0.3	4	4
Histones	0.03	0.044	-9999	-0.23	2	2
ADRBK1	0.025	0.005	-9999	-10000	0	0
HDAC4	0.025	0.005	-9999	-10000	0	0
XPO1	0.026	0.002	-9999	-10000	0	0
HDAC5/ANKRA2	0.038	0.006	-9999	-10000	0	0
HDAC4/Ubc9	0.037	0.008	-9999	-10000	0	0
HDAC7	0.026	0.004	-9999	-10000	0	0
HDAC5/14-3-3 E	0.039	0.005	-9999	-10000	0	0
TUBA1B	0.026	0.004	-9999	-10000	0	0
HDAC6	0.026	0.002	-9999	-10000	0	0
HDAC5/RFXANK	0.037	0.011	-9999	-10000	0	0
CAMK4	-0.094	0.19	-9999	-0.43	121	121
Tubulin/HDAC6	0.051	0.012	-9999	-10000	0	0
SUMO1	0.026	0.002	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.025	0.005	-9999	-10000	0	0
GATA1	0.013	0.025	-9999	-0.13	7	7
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.026	0.002	-9999	-10000	0	0
NR3C1	0.026	0.004	-9999	-10000	0	0
SUMO1/HDAC4	0.04	0.021	-9999	-0.21	1	1
SRF	0.026	0.002	-9999	-10000	0	0
HDAC4/YWHAB	0.036	0.011	-9999	-10000	0	0
Tubulin	0.038	0.007	-9999	-10000	0	0
HDAC4/14-3-3 E	0.037	0.008	-9999	-10000	0	0
GNB1	0.022	0.01	-9999	-10000	0	0
RANGAP1	0.026	0.004	-9999	-10000	0	0
BCL6/BCoR	0.038	0.007	-9999	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0.05	0.014	-9999	-10000	0	0
HDAC4/SRF	-0.019	0.13	-9999	-0.26	119	119
HDAC4/ER alpha	0.026	0.054	-9999	-0.3	11	11
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.03	0.044	-9999	-0.23	2	2
cell motility	0.05	0.012	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.026	0.002	-9999	-10000	0	0
HDAC7/HDAC3	0.038	0.007	-9999	-10000	0	0
BCL6	0.026	0.004	-9999	-10000	0	0
HDAC4/CaMK II delta B	0.025	0.005	-9999	-10000	0	0
Hsp90/HDAC6	0.037	0.008	-9999	-10000	0	0
ESR1	0.011	0.07	-9999	-0.26	25	25
HDAC6/HDAC11	0.037	0.017	-9999	-0.3	1	1
Ran/GTP/Exportin 1	0.043	0.019	-9999	-0.21	1	1
NPC	0.016	0.001	-9999	-10000	0	0
MEF2C	0.019	0.04	-9999	-0.16	20	20
RAN	0.026	0.003	-9999	-10000	0	0
HDAC4/MEF2C	0.071	0.029	-9999	-0.22	2	2
GNG2	0.022	0.04	-9999	-0.43	4	4
NCOR2	0.026	0.003	-9999	-10000	0	0
TUBB2A	0.026	0.004	-9999	-10000	0	0
HDAC11	0.025	0.02	-9999	-0.43	1	1
HSP90AA1	0.025	0.005	-9999	-10000	0	0
RANBP2	0.026	0.002	-9999	-10000	0	0
ANKRA2	0.026	0.003	-9999	-10000	0	0
RFXANK	0.025	0.009	-9999	-10000	0	0
nuclear import	-0.032	0.01	-9999	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.017	0.044	-9999	-0.43	2	2
PLK4	0.016	0.05	-9999	-0.43	4	4
regulation of centriole replication	0.001	0.042	-9999	-0.28	6	6

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.022	0.01	-10000	0	-10000	0	0
mol:PIP3	0.009	0.016	-10000	0	-0.16	3	3
FRAP1	0.021	0.044	0.27	2	-0.31	2	4
AKT1	0.009	0.034	0.17	15	-0.18	1	16
INSR	0.025	0.005	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.023	0.027	-10000	0	-0.26	4	4
mol:GTP	0.032	0.038	0.2	1	-10000	0	1
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0.015	0.017	-10000	0	-0.16	1	1
TSC2	0.026	0.002	-10000	0	-10000	0	0
RHEB/GDP	0.015	0.025	-10000	0	-10000	0	0
TSC1	0.026	0.005	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.024	0.017	-10000	0	-0.18	3	3
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.028	0.023	-10000	0	-0.18	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.025	0.007	-10000	0	-10000	0	0
RPS6KB1	0.026	0.05	0.26	9	-0.32	1	10
MAP3K5	-0.005	0.051	-10000	0	-0.22	25	25
PIK3R1	0.026	0.003	-10000	0	-10000	0	0
apoptosis	-0.005	0.051	-10000	0	-0.22	25	25
mol:LY294002	0	0	-10000	0	-0.001	3	3
EIF4B	0.024	0.048	0.25	10	-0.28	1	11
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.038	0.033	0.19	3	-0.25	1	4
eIF4E/eIF4G1/eIF4A1	0.016	0.023	-10000	0	-0.2	2	2
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.041	0.019	-10000	0	-0.17	3	3
mTOR/RHEB/GTP/Raptor/GBL	0.007	0.022	0.13	4	-10000	0	4
FKBP1A	0.025	0.005	-10000	0	-10000	0	0
RHEB/GTP	0.025	0.032	0.18	1	-10000	0	1
mol:Amino Acids	0	0	-10000	0	-0.001	3	3
FKBP12/Rapamycin	0.019	0.004	-10000	0	-10000	0	0
PDPK1	-0.003	0.022	0.18	2	-0.23	1	3
EIF4E	0.026	0.004	-10000	0	-10000	0	0
ASK1/PP5C	0.005	0.14	-10000	0	-0.57	25	25
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.019	0.045	-10000	0	-0.23	11	11
TSC1/TSC2	0.039	0.048	0.27	6	-10000	0	6
tumor necrosis factor receptor activity	0	0	0.001	3	-10000	0	3
RPS6	0.024	0.01	-10000	0	-0.13	1	1
PPP5C	0.022	0.01	-10000	0	-10000	0	0
EIF4G1	0.026	0.004	-10000	0	-10000	0	0
IRS1	0.008	0.018	-10000	0	-0.2	3	3
INS	-0.018	0.037	-10000	0	-0.43	4	4
PTEN	0.025	0.006	-10000	0	-10000	0	0
PDK2	-0.003	0.021	0.18	2	-0.19	1	3
EIF4EBP1	0.003	0.15	-10000	0	-1.1	9	9
PIK3CA	0.025	0.02	-10000	0	-0.43	1	1
PPP2R5D	0.02	0.043	0.26	2	-0.28	2	4
peptide biosynthetic process	-0.008	0.033	0.18	10	-0.23	4	14
RHEB	0.02	0.011	-10000	0	-10000	0	0
EIF4A1	0.026	0.003	-10000	0	-10000	0	0
mol:Rapamycin	0	0.001	0.003	26	-10000	0	26
EEF2	-0.008	0.033	0.18	10	-0.23	4	14
eIF4E/4E-BP1	0.016	0.14	-10000	0	-1	9	9

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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
SMAD4	0.026	0.004	-9999	-10000	0	0
SMAD2	-0.001	0.035	-9999	-0.25	2	2
SMAD3	0.025	0.025	-9999	-10000	0	0
SMAD3/SMAD4	0.038	0.044	-9999	-0.71	1	1
SMAD4/Ubc9/PIASy	0.05	0.014	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	0.047	0.044	-9999	-10000	0	0
PPM1A	0.025	0.005	-9999	-10000	0	0
CALM1	0.025	0.009	-9999	-0.13	1	1
SMAD2/SMAD4	0.014	0.036	-9999	-0.23	2	2
MAP3K1	0.024	0.019	-9999	-10000	0	0
TRAP-1/SMAD4	0.027	0.06	-9999	-0.3	16	16
MAPK3	0.026	0.002	-9999	-10000	0	0
MAPK1	0.026	0.003	-9999	-10000	0	0
NUP214	0.025	0.005	-9999	-10000	0	0
CTDSP1	0.026	0.003	-9999	-10000	0	0
CTDSP2	0.025	0.006	-9999	-10000	0	0
CTDSPL	0.025	0.02	-9999	-0.43	1	1
KPNB1	0.026	0.003	-9999	-10000	0	0
TGFBRAP1	0.012	0.079	-9999	-0.43	16	16
UBE2I	0.026	0.002	-9999	-10000	0	0
NUP153	0.026	0.003	-9999	-10000	0	0
KPNA2	0.025	0.009	-9999	-10000	0	0
PIAS4	0.025	0.005	-9999	-10000	0	0

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.013	0.028	0.15	21	-10000	0	21
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.012	0.027	-10000	0	-10000	0	0
AP2	0.031	0.016	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.028	0.015	-10000	0	-10000	0	0
CLTB	0.026	0.004	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.018	0.007	-10000	0	-10000	0	0
CD4	0.022	0.032	-10000	0	-0.23	6	6
CLTA	0.026	0.005	-10000	0	-10000	0	0
mol:GTP	-0.001	0.001	-10000	0	-10000	0	0
ARFGAP1	0.007	0.004	-10000	0	-0.084	1	1
mol:PI-4-5-P2	0.004	0.017	-10000	0	-0.16	1	1
ARF1/GTP	0.025	0.015	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.01	0.005	-10000	0	-10000	0	0
mol:Choline	0.004	0.017	-10000	0	-0.17	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.021	0.015	-10000	0	-10000	0	0
DDEF1	0.003	0.017	-10000	0	-0.17	1	1
ARF1/GDP	0.002	0.018	-10000	0	-10000	0	0
AP2M1	0.026	0.004	-10000	0	-10000	0	0
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	0.008	0.009	-10000	0	-10000	0	0
Rac/GTP	0.014	0.011	-10000	0	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.028	0.021	-10000	0	-10000	0	0
ARFIP2	0.023	0.008	-10000	0	-10000	0	0
COPA	0.026	0.004	-10000	0	-10000	0	0
RAC1	0.023	0.009	-10000	0	-10000	0	0
ARF1/GTP/coatomer protein complex	0.013	0.023	-10000	0	-10000	0	0
ARF1/GTP/ARHGAP10	0.014	0.011	-10000	0	-10000	0	0
GGA3	0.025	0.005	-10000	0	-10000	0	0
ARF1/GTP/Membrin	0.019	0.019	-10000	0	-10000	0	0
AP2A1	0.021	0.01	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.014	0.015	-10000	0	-10000	0	0
ARF1/GDP/Membrin	0.022	0.019	-10000	0	-0.21	1	1
Arfaptin 2/Rac/GDP	0.029	0.014	-10000	0	-10000	0	0
CYTH2	0.022	0.011	-10000	0	-10000	0	0
ARF1/GTP/GGA3	0.027	0.019	-10000	0	-10000	0	0
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.017	0.007	-10000	0	-10000	0	0
mol:Brefeldin A	0	0	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.008	0.042	-10000	0	-0.26	2	2
PLD2	0.004	0.017	-10000	0	-0.17	1	1
ARF-GAP1/v-SNARE	0.007	0.004	-10000	0	-0.084	1	1
PIP5K1A	0.004	0.017	-10000	0	-0.16	1	1
ARF1/GTP/Membrin/GBF1/p115	0.014	0.024	-10000	0	-10000	0	0
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.004	0.017	-10000	0	-0.17	1	1
KDEL Receptor/Ligand/ARF-GAP1	0.007	0.004	-10000	0	-0.084	1	1
GOSR2	0.012	0.009	-10000	0	-10000	0	0
USO1	0.006	0.045	-10000	0	-0.33	9	9
GBF1	0.005	0.046	-10000	0	-0.32	10	10
ARF1/GTP/Arfaptin 2	0.027	0.021	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.039	0.029	-10000	0	-0.23	2	2

×

Alternative NF-kappaB 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
IKK alpha homodimer	0.037	0.009	-9999	-10000	0	0
FBXW11	0.026	0.004	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.026	0.004	-9999	-10000	0	0
CHUK	0.025	0.005	-9999	-10000	0	0
NF kappa B2 p100/RelB	0.059	0.04	-9999	-0.22	3	3
NFKB1	0.026	0.004	-9999	-10000	0	0
MAP3K14	0.026	0.003	-9999	-10000	0	0
NF kappa B1 p50/RelB	0.031	0.018	-9999	-10000	0	0
RELB	0.02	0.025	-9999	-0.43	1	1
NFKB2	0.023	0.03	-9999	-0.33	3	3
NF kappa B2 p52/RelB	0.026	0.027	-9999	-0.22	4	4
regulation of B cell activation	0.026	0.027	-9999	-0.22	4	4

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.022	0.01	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0.007	0.005	-9999	-10000	0	0
MDM2/SUMO1	0.041	0.02	-9999	-0.23	1	1
HDAC4	0.025	0.005	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	0.006	0.006	-9999	-10000	0	0
SUMO1	0.026	0.002	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.012	0.012	-9999	-0.26	1	1
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.011	0.002	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.026	0.003	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.026	0.002	-9999	-10000	0	0
SUMO1/HDAC4	0.04	0.021	-9999	-0.21	1	1
SUMO1/HDAC1	0.034	0.024	-9999	-0.23	1	1
RANGAP1	0.026	0.004	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	0.061	0.033	-9999	-0.24	5	5
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.015	0.003	-9999	-10000	0	0
Ran/GTP	0.029	0.019	-9999	-0.24	1	1
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.026	0.004	-9999	-10000	0	0
UBE2I	0.026	0.002	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.027	0.017	-9999	-0.21	1	1
NPC	0.016	0.001	-9999	-10000	0	0
PIAS2	0.025	0.02	-9999	-0.43	1	1
PIAS1	0.022	0.04	-9999	-0.43	4	4
EntrezGene:9972	0	0	-9999	-10000	0	0

pid_entity	TCGA.WY.A85E	TCGA.WY.A85D	TCGA.WY.A85C	TCGA.WY.A85B
109_MAP3K5	0.16	-0.16	0.064	-0.19
47_PPARGC1A	0.026	0.026	0.026	0.026
105_BMP4	0.026	0.026	0.026	0.026
105_BMP6	0.026	0.026	0.026	0.026
105_BMP7	0.026	0.026	0.026	0.026
105_BMP2	0.026	0.026	0.026	0.026
131_RELN/VLDLR	0	0.068	-0.23	0
30_TGFB1/TGF beta receptor Type II	0.026	0.026	0.027	0.026
84_STAT5B	0.097	0.033	0.066	0.033
84_STAT5A	0.097	0.033	0.066	0.033