PARADIGM pathway analysis of mRNASeq expression data - Kidney Renal Papillary Cell Carcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
Nephrin/Neph1 signaling in the kidney podocyte	134
EGFR-dependent Endothelin signaling events	113
Angiopoietin receptor Tie2-mediated signaling	101
FOXA2 and FOXA3 transcription factor networks	92
PDGFR-alpha signaling pathway	66
Thromboxane A2 receptor signaling	55
Signaling mediated by p38-alpha and p38-beta	50
Glypican 1 network	39
Endothelins	39
BMP receptor signaling	37

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
Nephrin/Neph1 signaling in the kidney podocyte	0.4621	134	4557	34	-0.3	0.01	1000	-1000	-0.015	-1000
EGFR-dependent Endothelin signaling events	0.3897	113	2380	21	-0.4	0.015	1000	-1000	-0.014	-1000
Angiopoietin receptor Tie2-mediated signaling	0.3483	101	8891	88	-0.8	0.087	1000	-1000	-0.047	-1000
FOXA2 and FOXA3 transcription factor networks	0.3172	92	4273	46	-1	0.013	1000	-1000	-0.055	-1000
PDGFR-alpha signaling pathway	0.2276	66	2922	44	-0.2	0.021	1000	-1000	-0.019	-1000
Thromboxane A2 receptor signaling	0.1897	55	5837	105	-0.4	0.075	1000	-1000	-0.034	-1000
Signaling mediated by p38-alpha and p38-beta	0.1724	50	2217	44	-0.17	0.01	1000	-1000	-0.023	-1000
Glypican 1 network	0.1345	39	1909	48	-0.23	0.02	1000	-1000	-0.017	-1000
Endothelins	0.1345	39	3801	96	-0.53	0.02	1000	-1000	-0.029	-1000
BMP receptor signaling	0.1276	37	3056	81	-0.26	0.02	1000	-1000	-0.039	-1000
Arf6 signaling events	0.1207	35	2186	62	-0.4	0.025	1000	-1000	-0.02	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.1172	34	2660	78	-0.2	0.058	1000	-1000	-0.047	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.1103	32	4013	125	-0.11	0.025	1000	-1000	-0.033	-1000
FOXM1 transcription factor network	0.1069	31	1618	51	-0.031	0.24	1000	-1000	-0.082	-1000
HIF-1-alpha transcription factor network	0.1034	30	2338	76	-0.082	0.21	1000	-1000	-0.052	-1000
Integrins in angiogenesis	0.1000	29	2438	84	-0.29	0.023	1000	-1000	-0.028	-1000
IL4-mediated signaling events	0.0966	28	2613	91	-0.74	0.41	1000	-1000	-0.14	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0897	26	1803	68	-0.37	0.061	1000	-1000	-0.056	-1000
amb2 Integrin signaling	0.0793	23	1922	82	-0.26	0.013	1000	-1000	-0.022	-1000
S1P1 pathway	0.0793	23	846	36	-0.17	0.01	1000	-1000	-0.02	-1000
Signaling events mediated by PTP1B	0.0724	21	1622	76	-0.4	0.072	1000	-1000	-0.026	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0724	21	1591	74	-0.4	0.028	1000	-1000	-0.04	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0724	21	2534	120	-0.16	0.091	1000	-1000	-0.033	-1000
Glucocorticoid receptor regulatory network	0.0621	18	2059	114	-0.47	0.098	1000	-1000	-0.038	-1000
TCR signaling in naïve CD8+ T cells	0.0586	17	1616	93	-0.31	0.17	1000	-1000	-0.04	-1000
Signaling events regulated by Ret tyrosine kinase	0.0552	16	1319	82	-0.057	0.01	1000	-1000	-0.04	-1000
Ephrin A reverse signaling	0.0517	15	105	7	-0.023	0.002	1000	-1000	-0.007	-1000
FoxO family signaling	0.0517	15	1002	64	-0.8	0.073	1000	-1000	-0.035	-1000
Nongenotropic Androgen signaling	0.0517	15	781	52	-0.1	0.048	1000	-1000	-0.02	-1000
Plasma membrane estrogen receptor signaling	0.0517	15	1324	86	-0.1	0.027	1000	-1000	-0.04	-1000
LPA4-mediated signaling events	0.0483	14	179	12	-0.12	0.005	1000	-1000	-0.009	-1000
Calcium signaling in the CD4+ TCR pathway	0.0483	14	436	31	-0.058	0.016	1000	-1000	-0.037	-1000
S1P3 pathway	0.0483	14	608	42	-0.085	0.015	1000	-1000	-0.035	-1000
E-cadherin signaling in keratinocytes	0.0483	14	620	43	-0.15	0.011	1000	-1000	-0.016	-1000
E-cadherin signaling events	0.0483	14	72	5	-0.027	0.01	1000	-1000	-0.002	-1000
Signaling events mediated by the Hedgehog family	0.0414	12	665	52	-0.032	0.015	1000	-1000	-0.029	-1000
IL27-mediated signaling events	0.0414	12	630	51	-0.92	0.34	1000	-1000	-0.03	-1000
IL6-mediated signaling events	0.0414	12	905	75	-0.19	0.035	1000	-1000	-0.038	-1000
Syndecan-1-mediated signaling events	0.0379	11	402	34	-0.021	0.019	1000	-1000	-0.022	-1000
p75(NTR)-mediated signaling	0.0379	11	1444	125	-0.25	0.028	1000	-1000	-0.039	-1000
TCGA08_rtk_signaling	0.0379	11	304	26	-0.16	0.021	1000	-1000	-0.004	-1000
E-cadherin signaling in the nascent adherens junction	0.0379	11	871	76	-0.027	0.019	1000	-1000	-0.033	-1000
Coregulation of Androgen receptor activity	0.0345	10	787	76	-0.54	0.017	1000	-1000	-0.028	-1000
IL12-mediated signaling events	0.0345	10	938	87	-0.092	0.089	1000	-1000	-0.091	-1000
EPHB forward signaling	0.0345	10	903	85	-0.12	0.044	1000	-1000	-0.035	-1000
ErbB4 signaling events	0.0310	9	624	69	-0.16	0.078	1000	-1000	-0.02	-1000
Osteopontin-mediated events	0.0310	9	360	38	-0.058	0.016	1000	-1000	-0.022	-1000
Noncanonical Wnt signaling pathway	0.0310	9	249	26	-0.071	0.016	1000	-1000	-0.019	-1000
S1P5 pathway	0.0310	9	153	17	-0.029	0.01	1000	-1000	-0.014	-1000
S1P4 pathway	0.0310	9	225	25	-0.029	0.019	1000	-1000	-0.016	-1000
Regulation of nuclear SMAD2/3 signaling	0.0276	8	1196	136	-0.33	0.048	1000	-1000	-0.031	-1000
Presenilin action in Notch and Wnt signaling	0.0276	8	496	61	-0.12	0.074	1000	-1000	-0.039	-1000
Ceramide signaling pathway	0.0276	8	680	76	-0.4	0.18	1000	-1000	-0.025	-1000
Reelin signaling pathway	0.0276	8	499	56	-0.095	0.034	1000	-1000	-0.015	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0276	8	464	52	-0.18	0.04	1000	-1000	-0.026	-1000
Regulation of Telomerase	0.0276	8	836	102	-0.39	0.027	1000	-1000	-0.042	-1000
Visual signal transduction: Rods	0.0276	8	465	52	-0.11	0.016	1000	-1000	-0.015	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0241	7	217	28	-0.085	0.038	1000	-1000	-0.018	-1000
Fc-epsilon receptor I signaling in mast cells	0.0241	7	698	97	-0.058	0.063	1000	-1000	-0.039	-1000
IL23-mediated signaling events	0.0241	7	458	60	-0.013	0.093	1000	-1000	-0.067	-1000
Regulation of Androgen receptor activity	0.0241	7	536	70	-0.66	0.016	1000	-1000	-0.036	-1000
Caspase cascade in apoptosis	0.0207	6	470	74	-0.37	0.027	1000	-1000	-0.018	-1000
Effects of Botulinum toxin	0.0207	6	177	26	-0.12	0.016	1000	-1000	-0.012	-1000
Wnt signaling	0.0207	6	42	7	-0.009	0.01	1000	-1000	-0.013	-1000
Syndecan-4-mediated signaling events	0.0207	6	442	67	-0.24	0.035	1000	-1000	-0.02	-1000
Class IB PI3K non-lipid kinase events	0.0207	6	18	3	0	0	1000	-1000	-0.002	-1000
Syndecan-2-mediated signaling events	0.0172	5	379	69	-0.26	0.023	1000	-1000	-0.015	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0172	5	432	85	-0.091	0.022	1000	-1000	-0.024	-1000
IL1-mediated signaling events	0.0172	5	358	62	-0.11	0.027	1000	-1000	-0.026	-1000
BCR signaling pathway	0.0172	5	565	99	-0.031	0.041	1000	-1000	-0.037	-1000
PDGFR-beta signaling pathway	0.0172	5	554	97	-0.007	0.031	1000	-1000	-0.031	-1000
Ras signaling in the CD4+ TCR pathway	0.0172	5	92	17	-0.021	0.015	1000	-1000	-0.02	-1000
Syndecan-3-mediated signaling events	0.0138	4	143	35	-0.091	0.028	1000	-1000	-0.017	-1000
Regulation of p38-alpha and p38-beta	0.0138	4	221	54	-0.1	0.039	1000	-1000	-0.032	-1000
LPA receptor mediated events	0.0138	4	454	102	-0.085	0.051	1000	-1000	-0.036	-1000
ErbB2/ErbB3 signaling events	0.0103	3	225	65	-0.005	0.11	1000	-1000	-0.024	-1000
Cellular roles of Anthrax toxin	0.0103	3	142	39	-0.091	0.013	1000	-1000	-0.01	-1000
IFN-gamma pathway	0.0103	3	251	68	-0.17	0.033	1000	-1000	-0.041	-1000
Nectin adhesion pathway	0.0103	3	228	63	-0.027	0.023	1000	-1000	-0.035	-1000
HIF-2-alpha transcription factor network	0.0103	3	137	43	-0.16	0.084	1000	-1000	-0.043	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0103	3	291	83	-0.18	0.021	1000	-1000	-0.03	-1000
Canonical Wnt signaling pathway	0.0103	3	196	51	-0.12	0.074	1000	-1000	-0.03	-1000
IGF1 pathway	0.0103	3	223	57	-0.011	0.024	1000	-1000	-0.024	-1000
Insulin Pathway	0.0103	3	224	74	-0.021	0.029	1000	-1000	-0.027	-1000
Signaling events mediated by HDAC Class II	0.0069	2	171	75	-0.083	0.028	1000	-1000	-0.015	-1000
BARD1 signaling events	0.0069	2	161	57	-0.018	0.039	1000	-1000	-0.026	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0069	2	152	54	-0.017	0.035	1000	-1000	-0.03	-1000
FAS signaling pathway (CD95)	0.0069	2	117	47	-0.089	0.015	1000	-1000	-0.029	-1000
Signaling mediated by p38-gamma and p38-delta	0.0069	2	32	15	-0.002	0.012	1000	-1000	-0.01	-1000
IL2 signaling events mediated by PI3K	0.0069	2	152	58	-0.007	0.063	1000	-1000	-0.031	-1000
Class I PI3K signaling events	0.0069	2	159	73	-0.015	0.036	1000	-1000	-0.026	-1000
VEGFR1 specific signals	0.0069	2	117	56	0	0.027	1000	-1000	-0.03	-1000
Aurora B signaling	0.0069	2	184	67	-0.21	0.032	1000	-1000	-0.024	-1000
Hedgehog signaling events mediated by Gli proteins	0.0034	1	98	65	-0.029	0.028	1000	-1000	-0.037	-1000
mTOR signaling pathway	0.0034	1	70	53	-0.002	0.017	1000	-1000	-0.025	-1000
Ephrin B reverse signaling	0.0034	1	87	48	-0.013	0.02	1000	-1000	-0.014	-1000
Signaling events mediated by HDAC Class I	0.0034	1	159	104	-0.083	0.028	1000	-1000	-0.03	-1000
Retinoic acid receptors-mediated signaling	0.0034	1	80	58	-0.031	0.029	1000	-1000	-0.025	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0034	1	62	33	-0.038	0.029	1000	-1000	-0.022	-1000
Signaling events mediated by PRL	0.0034	1	53	34	-0.018	0.015	1000	-1000	-0.023	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	10	23	0.002	0.026	1000	-1000	-0.023	-1000
Canonical NF-kappaB pathway	0.0000	0	6	39	0	0.035	1000	-1000	-0.028	-1000
PLK2 and PLK4 events	0.0000	0	0	3	0.008	0.01	1000	-1000	-0.006	-1000
Visual signal transduction: Cones	0.0000	0	28	38	0	0.017	1000	-1000	-0.012	-1000
Circadian rhythm pathway	0.0000	0	8	22	-0.007	0.026	1000	-1000	-0.027	-1000
JNK signaling in the CD4+ TCR pathway	0.0000	0	12	17	0.008	0.028	1000	-1000	-0.018	-1000
a4b1 and a4b7 Integrin signaling	0.0000	0	0	5	0.01	0.015	1000	-1000	-0.002	-1000
Aurora A signaling	0.0000	0	12	60	0	0.025	1000	-1000	-0.015	-1000
Arf6 downstream pathway	0.0000	0	0	43	-0.027	0.028	1000	-1000	-0.027	-1000
Aurora C signaling	0.0000	0	0	7	0	0.01	1000	-1000	-0.01	-1000
EPO signaling pathway	0.0000	0	45	55	-0.015	0.035	1000	-1000	-0.027	-1000
PLK1 signaling events	0.0000	0	58	85	-0.009	0.031	1000	-1000	-0.023	-1000
Insulin-mediated glucose transport	0.0000	0	8	32	-0.007	0.02	1000	-1000	-0.019	-1000
Class I PI3K signaling events mediated by Akt	0.0000	0	9	68	-0.026	0.032	1000	-1000	-0.022	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0000	0	5	37	0	0.029	1000	-1000	-0.016	-1000
Signaling events mediated by HDAC Class III	0.0000	0	18	40	-0.018	0.018	1000	-1000	-0.009	-1000
TRAIL signaling pathway	0.0000	0	3	48	0	0.029	1000	-1000	-0.023	-1000
ceramide signaling pathway	0.0000	0	17	49	0	0.025	1000	-1000	-0.023	-1000
TCGA08_p53	0.0000	0	0	7	0	0.01	1000	-1000	-0.001	-1000
Paxillin-dependent events mediated by a4b1	0.0000	0	2	36	-0.024	0.025	1000	-1000	-0.019	-1000
Atypical NF-kappaB pathway	0.0000	0	20	31	0	0.023	1000	-1000	-0.018	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0000	0	12	45	0.002	0.047	1000	-1000	-0.035	-1000
Glypican 2 network	0.0000	0	0	4	0.005	0.007	1000	-1000	-0.003	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	3	27	-0.001	0.025	1000	-1000	-0.02	-1000
IL2 signaling events mediated by STAT5	0.0000	0	0	22	0.004	0.048	1000	-1000	-0.035	-1000
Arf6 trafficking events	0.0000	0	11	71	-0.16	0.019	1000	-1000	-0.022	-1000
TCGA08_retinoblastoma	0.0000	0	5	8	-0.035	0.033	1000	-1000	-0.001	-1000
Rapid glucocorticoid signaling	0.0000	0	9	20	-0.001	0.013	1000	-1000	-0.007	-1000
p38 MAPK signaling pathway	0.0000	0	19	44	-0.001	0.023	1000	-1000	-0.025	-1000
Arf1 pathway	0.0000	0	0	54	0	0.019	1000	-1000	-0.019	-1000
Alternative NF-kappaB pathway	0.0000	0	0	13	0	0.029	1000	-1000	-0.002	-1000
Total	NA	1624	102591	7203	-19	5.4	131000	-131000	-3.5	-131000

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.25	0.18	0.36	195	-10000	0	195
KIRREL	-0.075	0.13	-10000	0	-0.48	27	27
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.25	0.18	-10000	0	-0.37	195	195
PLCG1	0.01	0	-10000	0	-10000	0	0
ARRB2	0.01	0.001	-10000	0	-10000	0	0
WASL	0.01	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.24	0.18	-10000	0	-0.33	216	216
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.25	0.19	-10000	0	-0.34	216	216
FYN	-0.23	0.17	-10000	0	-0.32	216	216
mol:Ca2+	-0.24	0.18	-10000	0	-0.33	216	216
mol:DAG	-0.24	0.18	-10000	0	-0.33	216	216
NPHS2	-0.2	0.22	-10000	0	-0.48	109	109
mol:IP3	-0.24	0.18	-10000	0	-0.33	216	216
regulation of endocytosis	-0.22	0.16	-10000	0	-0.3	216	216
Nephrin/NEPH1/podocin/Cholesterol	-0.25	0.18	-10000	0	-0.33	216	216
establishment of cell polarity	-0.25	0.18	-10000	0	-0.36	195	195
Nephrin/NEPH1/podocin/NCK1-2	-0.22	0.17	-10000	0	-0.3	216	216
Nephrin/NEPH1/beta Arrestin2	-0.22	0.17	-10000	0	-0.3	216	216
NPHS1	-0.3	0.22	-10000	0	-0.47	187	187
Nephrin/NEPH1/podocin	-0.24	0.17	-10000	0	-0.32	216	216
TJP1	0.01	0	-10000	0	-10000	0	0
NCK1	0.01	0	-10000	0	-10000	0	0
NCK2	0.01	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.24	0.18	-10000	0	-0.33	216	216
CD2AP	0.01	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.24	0.18	-10000	0	-0.33	216	216
GRB2	0.01	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.28	0.19	-10000	0	-0.35	235	235
cytoskeleton organization	-0.29	0.21	-10000	0	-0.39	216	216
Nephrin/NEPH1	-0.17	0.13	-10000	0	-0.26	195	195
Nephrin/NEPH1/ZO-1	-0.19	0.15	-10000	0	-0.29	195	195

×

EGFR-dependent Endothelin 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
HRAS	0.01	0	-9999	-10000	0	0
EGFR	0.01	0	-9999	-10000	0	0
EGF/EGFR	-0.2	0.078	-9999	-0.22	264	264
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.19	0.073	-9999	-0.22	261	261
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.01	0.093	-9999	-0.44	13	13
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.4	0.14	-9999	-0.44	261	261
EGF/EGFR dimer/SHC	-0.23	0.083	-9999	-0.26	261	261
mol:GDP	-0.19	0.072	-9999	-0.21	261	261
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.008	0.026	-9999	-0.44	1	1
GRB2/SOS1	0.015	0	-9999	-10000	0	0
HRAS/GTP	-0.18	0.065	-9999	-0.2	261	261
SHC1	0.01	0	-9999	-10000	0	0
HRAS/GDP	-0.18	0.068	-9999	-0.2	261	261
FRAP1	-0.18	0.064	-9999	-0.2	261	261
EGF/EGFR dimer	-0.28	0.097	-9999	-0.31	261	261
SOS1	0.01	0	-9999	-10000	0	0
GRB2	0.01	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.001	0.07	-9999	-0.31	14	14

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.54	0.52	-10000	0	-0.98	166	166
NCK1/PAK1/Dok-R	-0.25	0.22	-10000	0	-0.44	166	166
NCK1/Dok-R	-0.66	0.65	-10000	0	-1.2	166	166
PIK3CA	0.011	0.001	-10000	0	-10000	0	0
mol:beta2-estradiol	0.082	0.11	0.23	96	-10000	0	96
RELA	0.01	0	-10000	0	-10000	0	0
SHC1	0.008	0.002	-10000	0	-10000	0	0
Rac/GDP	0.007	0	-10000	0	-10000	0	0
F2	0.087	0.11	0.24	96	-10000	0	96
TNIP2	0.01	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.6	0.59	-10000	0	-1.1	166	166
FN1	0.009	0.003	-10000	0	-10000	0	0
PLD2	-0.7	0.68	-10000	0	-1.2	166	166
PTPN11	0.01	0	-10000	0	-10000	0	0
GRB14	-0.021	0.11	-10000	0	-0.44	20	20
ELK1	-0.61	0.58	-10000	0	-1.1	166	166
GRB7	0.01	0	-10000	0	-10000	0	0
PAK1	0.01	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.64	0.63	-10000	0	-1.1	166	166
CDKN1A	-0.36	0.34	-10000	0	-0.65	165	165
ITGA5	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.66	0.65	-10000	0	-1.2	166	166
CRK	0.01	0	-10000	0	-10000	0	0
mol:NO	-0.38	0.37	-10000	0	-0.7	166	166
PLG	-0.8	0.66	-10000	0	-1.3	166	166
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.51	0.48	-10000	0	-0.92	166	166
GRB2	0.01	0	-10000	0	-10000	0	0
PIK3R1	0.008	0.002	-10000	0	-10000	0	0
ANGPT2	-0.26	0.28	-10000	0	-0.58	108	108
BMX	-0.7	0.68	-10000	0	-1.2	166	166
ANGPT1	-0.44	0.57	-10000	0	-1.2	96	96
tube development	-0.42	0.39	-10000	0	-0.74	166	166
ANGPT4	0.006	0.006	-10000	0	-10000	0	0
response to hypoxia	-0.037	0.034	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.73	0.71	-10000	0	-1.3	166	166
alpha5/beta1 Integrin	0.015	0	-10000	0	-10000	0	0
FGF2	0.006	0.045	-10000	0	-0.44	3	3
STAT5A (dimer)	-0.48	0.46	-10000	0	-0.86	166	166
mol:L-citrulline	-0.38	0.37	-10000	0	-0.7	166	166
AGTR1	-0.13	0.21	-10000	0	-0.44	91	91
MAPK14	-0.72	0.68	-10000	0	-1.3	166	166
Tie2/SHP2	-0.58	0.57	-10000	0	-1.1	149	149
TEK	-0.64	0.63	-10000	0	-1.2	149	149
RPS6KB1	-0.52	0.49	-10000	0	-0.93	166	166
Angiotensin II/AT1	-0.091	0.15	-10000	0	-0.31	91	91
Tie2/Ang1/GRB2	-0.72	0.71	-10000	0	-1.3	166	166
MAPK3	-0.62	0.6	-10000	0	-1.1	166	166
MAPK1	-0.62	0.6	-10000	0	-1.1	166	166
Tie2/Ang1/GRB7	-0.72	0.71	-10000	0	-1.3	166	166
NFKB1	0.01	0	-10000	0	-10000	0	0
MAPK8	-0.7	0.68	-10000	0	-1.2	166	166
PI3K	-0.64	0.62	-10000	0	-1.2	166	166
FES	-0.71	0.68	-10000	0	-1.3	166	166
Crk/Dok-R	-0.66	0.65	-10000	0	-1.2	166	166
Tie2/Ang1/ABIN2	-0.72	0.71	-10000	0	-1.3	166	166
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.47	0.45	-10000	0	-0.85	166	166
STAT5A	0.01	0	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.52	0.49	-10000	0	-0.93	166	166
Tie2/Ang2	-0.6	0.57	-10000	0	-1.1	166	166
Tie2/Ang1	-0.78	0.77	-10000	0	-1.4	166	166
FOXO1	-0.48	0.46	-10000	0	-0.86	166	166
ELF1	-0.048	0.056	-10000	0	-10000	0	0
ELF2	-0.7	0.68	-10000	0	-1.2	166	166
mol:Choline	-0.65	0.62	-10000	0	-1.2	166	166
cell migration	-0.14	0.12	-10000	0	-0.24	166	166
FYN	-0.48	0.46	-10000	0	-0.86	166	166
DOK2	0.008	0.026	-10000	0	-0.44	1	1
negative regulation of cell cycle	-0.32	0.31	-10000	0	-0.59	166	166
ETS1	-0.076	0.11	-10000	0	-0.23	96	96
PXN	-0.41	0.39	-10000	0	-0.75	166	166
ITGB1	0.01	0	-10000	0	-10000	0	0
NOS3	-0.44	0.43	-10000	0	-0.81	166	166
RAC1	0.01	0	-10000	0	-10000	0	0
TNF	-0.076	0.11	-10000	0	-0.24	94	94
MAPKKK cascade	-0.65	0.62	-10000	0	-1.2	166	166
RASA1	0.01	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.72	0.72	-10000	0	-1.3	166	166
NCK1	0.01	0	-10000	0	-10000	0	0
vasculogenesis	-0.34	0.33	-10000	0	-0.62	166	166
mol:Phosphatidic acid	-0.65	0.62	-10000	0	-1.2	166	166
mol:Angiotensin II	0.001	0.002	-10000	0	-10000	0	0
mol:NADP	-0.38	0.37	-10000	0	-0.7	166	166
Rac1/GTP	-0.48	0.44	-10000	0	-0.86	166	166
MMP2	-0.7	0.68	-10000	0	-1.2	166	166

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.45	0.33	-10000	0	-0.83	105	105
PCK1	-1	0.61	-10000	0	-1.4	187	187
HNF4A	-0.51	0.42	-10000	0	-1	91	91
KCNJ11	-0.48	0.33	-10000	0	-0.86	103	103
AKT1	-0.26	0.13	-10000	0	-0.39	113	113
response to starvation	-0.003	0.012	-10000	0	-0.14	1	1
DLK1	-0.49	0.34	-10000	0	-0.88	105	105
NKX2-1	-0.14	0.14	-10000	0	-0.47	5	5
ACADM	-0.46	0.33	-10000	0	-0.82	107	107
TAT	-0.43	0.2	-10000	0	-0.6	133	133
CEBPB	-0.039	0.034	-10000	0	-10000	0	0
CEBPA	-0.033	0.039	-10000	0	-0.44	1	1
TTR	-0.69	0.37	-10000	0	-0.82	215	215
PKLR	-0.54	0.44	-10000	0	-1	109	109
APOA1	-0.59	0.48	-10000	0	-1.2	96	96
CPT1C	-0.46	0.34	-10000	0	-0.86	103	103
ALAS1	-0.22	0.13	-10000	0	-10000	0	0
TFRC	-0.58	0.28	-10000	0	-0.73	193	193
FOXF1	0.006	0.038	-10000	0	-0.44	2	2
NF1	0.013	0	-10000	0	-10000	0	0
HNF1A (dimer)	-0.053	0.072	-10000	0	-0.25	14	14
CPT1A	-0.45	0.33	-10000	0	-0.83	105	105
HMGCS1	-0.45	0.33	-10000	0	-0.83	104	104
NR3C1	0.007	0.04	-10000	0	-0.17	1	1
CPT1B	-0.45	0.33	-10000	0	-0.82	106	106
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.012	0.009	-10000	0	-10000	0	0
GCK	-0.45	0.33	-10000	0	-0.83	105	105
CREB1	-0.09	0.065	-10000	0	-0.18	59	59
IGFBP1	-0.27	0.32	-10000	0	-1.3	21	21
PDX1	-0.26	0.16	-10000	0	-0.54	41	41
UCP2	-0.46	0.33	-10000	0	-0.83	105	105
ALDOB	-0.94	0.32	-10000	0	-1	275	275
AFP	-0.4	0.27	-10000	0	-0.56	136	136
BDH1	-0.46	0.33	-10000	0	-0.83	106	106
HADH	-0.48	0.33	-10000	0	-0.86	103	103
F2	-0.54	0.42	-10000	0	-1.1	95	95
HNF1A	-0.053	0.072	-10000	0	-0.25	14	14
G6PC	-0.94	0.54	-10000	0	-1.3	197	197
SLC2A2	-0.45	0.48	-10000	0	-1.2	65	65
INS	0.003	0.038	0.15	6	-10000	0	6
FOXA1	-0.18	0.1	-10000	0	-0.23	205	205
FOXA3	-0.4	0.16	-10000	0	-0.42	268	268
FOXA2	-0.56	0.37	-10000	0	-0.93	116	116
ABCC8	-0.48	0.33	-10000	0	-0.87	101	101
ALB	-0.84	0.29	-10000	0	-0.93	256	256

×

PDGFR-alpha signaling pathway

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
PDGFRA	-0.17	0.22	-9999	-0.45	109	109
PDGF/PDGFRA/CRKL	-0.11	0.16	-9999	-0.31	109	109
positive regulation of JUN kinase activity	-0.072	0.12	-9999	-0.23	109	109
CRKL	0.01	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.11	0.15	-9999	-0.31	109	109
AP1	-0.2	0.34	-9999	-0.96	44	44
mol:IP3	-0.12	0.16	-9999	-0.33	109	109
PLCG1	-0.12	0.16	-9999	-0.33	109	109
PDGF/PDGFRA/alphaV Integrin	-0.11	0.16	-9999	-0.31	109	109
RAPGEF1	0.01	0	-9999	-10000	0	0
CRK	0.01	0	-9999	-10000	0	0
mol:Ca2+	-0.12	0.16	-9999	-0.33	109	109
CAV3	0.002	0.004	-9999	-10000	0	0
CAV1	0.01	0.001	-9999	-10000	0	0
SHC/Grb2/SOS1	-0.072	0.12	-9999	-0.23	109	109
PDGF/PDGFRA/Shf	-0.11	0.16	-9999	-0.31	109	109
FOS	-0.2	0.33	-9999	-0.95	44	44
JUN	-0.018	0.026	-9999	-10000	0	0
oligodendrocyte development	-0.11	0.16	-9999	-0.31	109	109
GRB2	0.01	0	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
mol:DAG	-0.12	0.16	-9999	-0.33	109	109
PDGF/PDGFRA	-0.17	0.22	-9999	-0.45	109	109
actin cytoskeleton reorganization	-0.11	0.16	-9999	-0.31	109	109
SRF	0.015	0.009	-9999	-10000	0	0
SHC1	0.01	0	-9999	-10000	0	0
PI3K	-0.085	0.13	-9999	-0.26	109	109
PDGF/PDGFRA/Crk/C3G	-0.085	0.13	-9999	-0.26	109	109
JAK1	-0.11	0.15	-9999	-0.31	109	109
ELK1/SRF	-0.089	0.13	-9999	-0.25	109	109
SHB	0.01	0	-9999	-10000	0	0
SHF	0.01	0	-9999	-10000	0	0
CSNK2A1	0.021	0.017	-9999	-10000	0	0
GO:0007205	-0.13	0.18	-9999	-0.36	109	109
SOS1	0.01	0	-9999	-10000	0	0
Ras protein signal transduction	-0.072	0.12	-9999	-0.23	109	109
PDGF/PDGFRA/SHB	-0.11	0.16	-9999	-0.31	109	109
PDGF/PDGFRA/Caveolin-1	-0.11	0.16	-9999	-0.31	109	109
ITGAV	0.01	0	-9999	-10000	0	0
ELK1	-0.12	0.16	-9999	-0.31	109	109
PIK3CA	0.01	0	-9999	-10000	0	0
PDGF/PDGFRA/Crk	-0.11	0.16	-9999	-0.31	109	109
JAK-STAT cascade	-0.11	0.15	-9999	-0.31	109	109
cell proliferation	-0.11	0.16	-9999	-0.31	109	109

×

Thromboxane A2 receptor 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
TGM2	0.008	0.003	-10000	0	-10000	0	0
GNB1/GNG2	-0.091	0.087	-10000	0	-0.18	148	148
AKT1	-0.08	0.12	0.24	1	-0.19	148	149
EGF	-0.4	0.14	-10000	0	-0.44	261	261
mol:TXA2	-0.001	0.001	-10000	0	-10000	0	0
FGR	-0.006	0.052	-10000	0	-0.48	1	1
mol:Ca2+	-0.13	0.17	0.29	1	-0.29	148	149
LYN	-0.005	0.048	-10000	0	-0.31	1	1
RhoA/GTP	-0.06	0.065	-10000	0	-0.12	148	148
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.15	0.19	0.3	1	-0.32	148	149
GNG2	0.01	0	-10000	0	-10000	0	0
ARRB2	0.01	0.001	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.02	0.079	-10000	0	-0.32	8	8
G beta5/gamma2	-0.12	0.12	-10000	0	-0.23	148	148
PRKCH	-0.15	0.19	0.3	1	-0.34	148	149
DNM1	0.005	0.027	-10000	0	-0.44	1	1
TXA2/TP beta/beta Arrestin3	0.002	0.016	-10000	0	-0.19	1	1
mol:GTP	-0.001	0.001	-10000	0	-10000	0	0
PTGDR	0.009	0.001	-10000	0	-10000	0	0
G12 family/GTP	-0.15	0.14	-10000	0	-0.29	148	148
ADRBK1	0.01	0	-10000	0	-10000	0	0
ADRBK2	0.01	0	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0.012	0.001	-10000	0	-10000	0	0
mol:GDP	0.075	0.11	0.3	15	-0.19	1	16
mol:NADP	-0.006	0.082	-10000	0	-0.44	10	10
RAB11A	0.01	0	-10000	0	-10000	0	0
PRKG1	-0.1	0.2	-10000	0	-0.44	73	73
mol:IP3	-0.16	0.2	0.31	1	-0.36	148	149
cell morphogenesis	0.012	0.001	-10000	0	-10000	0	0
PLCB2	-0.22	0.26	0.33	1	-0.48	148	149
mol:cGMP	-0.001	0.001	-10000	0	-10000	0	0
BLK	-0.006	0.048	-10000	0	-0.31	1	1
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.007	0.052	-10000	0	-0.48	1	1
RHOA	0.01	0	-10000	0	-10000	0	0
PTGIR	0.006	0.037	-10000	0	-0.44	2	2
PRKCB1	-0.16	0.2	0.3	1	-0.36	148	149
GNAQ	0.01	0	-10000	0	-10000	0	0
mol:L-citrulline	-0.006	0.082	-10000	0	-0.44	10	10
TXA2/TXA2-R family	-0.23	0.28	0.34	1	-0.5	148	149
LCK	-0.005	0.048	-10000	0	-0.31	1	1
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.001	0.055	-10000	0	-0.37	1	1
TXA2-R family/G12 family/GDP/G beta/gamma	0.012	0.019	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.003	0.056	-10000	0	-0.37	1	1
MAPK14	-0.094	0.13	0.25	1	-0.22	148	149
TGM2/GTP	-0.18	0.22	0.32	1	-0.39	148	149
MAPK11	-0.094	0.13	0.25	1	-0.22	148	149
ARHGEF1	-0.074	0.1	0.19	1	-0.17	148	149
GNAI2	0.01	0	-10000	0	-10000	0	0
JNK cascade	-0.17	0.21	0.32	1	-0.37	148	149
RAB11/GDP	0.011	0.001	-10000	0	-10000	0	0
ICAM1	-0.12	0.16	0.24	2	-0.27	148	150
cAMP biosynthetic process	-0.15	0.19	0.28	1	-0.33	148	149
Gq family/GTP/EBP50	-0.031	0.079	-10000	0	-0.17	66	66
actin cytoskeleton reorganization	0.012	0.001	-10000	0	-10000	0	0
SRC	-0.005	0.048	-10000	0	-0.31	1	1
GNB5	0.01	0	-10000	0	-10000	0	0
GNB1	0.01	0	-10000	0	-10000	0	0
EGF/EGFR	-0.081	0.052	-10000	0	-0.21	21	21
VCAM1	-0.12	0.16	0.21	4	-0.27	146	150
TP beta/Gq family/GDP/G beta5/gamma2	-0.02	0.079	-10000	0	-0.32	8	8
platelet activation	-0.12	0.17	0.3	1	-0.29	148	149
PGI2/IP	0.005	0.026	-10000	0	-0.31	2	2
PRKACA	0.007	0.019	-10000	0	-0.22	2	2
Gq family/GDP/G beta5/gamma2	-0.02	0.069	-10000	0	-0.28	8	8
TXA2/TP beta/beta Arrestin2	0.006	0.03	-10000	0	-0.46	1	1
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.009	0.062	-10000	0	-0.23	21	21
mol:DAG	-0.18	0.23	0.32	1	-0.4	148	149
EGFR	0.01	0	-10000	0	-10000	0	0
TXA2/TP alpha	-0.2	0.25	0.33	1	-0.44	148	149
Gq family/GTP	-0.038	0.093	-10000	0	-0.2	67	67
YES1	-0.005	0.048	-10000	0	-0.31	1	1
GNAI2/GTP	-0.008	0.053	-10000	0	-0.35	1	1
PGD2/DP	0.007	0.001	-10000	0	-10000	0	0
SLC9A3R1	0.01	0	-10000	0	-10000	0	0
FYN	-0.005	0.048	-10000	0	-0.31	1	1
mol:NO	-0.006	0.082	-10000	0	-0.44	10	10
GNA15	0.009	0.002	-10000	0	-10000	0	0
PGK/cGMP	-0.065	0.13	-10000	0	-0.27	79	79
RhoA/GDP	0.011	0.001	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0.009	0.055	-10000	0	-0.31	1	1
NOS3	-0.006	0.082	-10000	0	-0.44	10	10
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCA	-0.15	0.19	0.3	1	-0.34	148	149
PRKCB	-0.15	0.19	0.3	1	-0.34	148	149
PRKCE	-0.16	0.2	0.3	1	-0.34	148	149
PRKCD	-0.17	0.21	0.3	1	-0.37	148	149
PRKCG	-0.16	0.2	0.3	1	-0.35	148	149
muscle contraction	-0.21	0.26	0.33	1	-0.45	148	149
PRKCZ	-0.14	0.19	0.3	1	-0.32	148	149
ARR3	0.002	0.004	-10000	0	-10000	0	0
TXA2/TP beta	-0.001	0.058	-10000	0	-0.21	15	15
PRKCQ	-0.16	0.2	0.3	1	-0.34	148	149
MAPKKK cascade	-0.2	0.24	0.32	1	-0.42	148	149
SELE	-0.18	0.21	0.28	1	-0.38	148	149
TP beta/GNAI2/GDP/G beta/gamma	0.01	0.058	-10000	0	-0.37	1	1
ROCK1	0.01	0	-10000	0	-10000	0	0
GNA14	-0.085	0.18	-10000	0	-0.44	61	61
chemotaxis	-0.27	0.32	0.36	1	-0.58	148	149
GNA12	0.01	0	-10000	0	-10000	0	0
GNA13	0.01	0.001	-10000	0	-10000	0	0
GNA11	-0.001	0.069	-10000	0	-0.44	7	7
Rac1/GTP	0.006	0.001	-10000	0	-10000	0	0

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.17	0.39	-9999	-0.87	63	63
MKNK1	0.01	0	-9999	-10000	0	0
MAPK14	-0.051	0.14	-9999	-0.3	63	63
ATF2/c-Jun	-0.037	0.11	-9999	-0.4	8	8
MAPK11	-0.051	0.14	-9999	-0.3	63	63
MITF	-0.063	0.16	-9999	-0.36	64	64
MAPKAPK5	-0.062	0.16	-9999	-0.36	63	63
KRT8	-0.062	0.16	-9999	-0.36	63	63
MAPKAPK3	0.01	0	-9999	-10000	0	0
MAPKAPK2	0.01	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.078	0.2	-9999	-0.45	63	63
CEBPB	-0.062	0.16	-9999	-0.36	63	63
SLC9A1	-0.062	0.16	-9999	-0.36	63	63
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.059	0.16	-9999	-0.35	63	63
p38alpha-beta/MNK1	-0.055	0.17	-9999	-0.36	63	63
JUN	-0.037	0.11	-9999	-0.4	8	8
PPARGC1A	-0.07	0.17	-9999	-0.37	68	68
USF1	-0.062	0.16	-9999	-0.36	63	63
RAB5/GDP/GDI1	-0.043	0.12	-9999	-0.27	63	63
NOS2	-0.11	0.29	-9999	-1.1	21	21
DDIT3	-0.062	0.16	-9999	-0.36	63	63
RAB5A	0.01	0	-9999	-10000	0	0
HSPB1	-0.049	0.13	-9999	-0.3	62	62
p38alpha-beta/HBP1	-0.055	0.17	-9999	-0.36	63	63
CREB1	-0.068	0.18	-9999	-0.39	63	63
RAB5/GDP	0.007	0	-9999	-10000	0	0
EIF4E	-0.055	0.14	-9999	-0.32	63	63
RPS6KA4	-0.062	0.16	-9999	-0.36	63	63
PLA2G4A	-0.061	0.16	-9999	-0.34	64	64
GDI1	-0.062	0.16	-9999	-0.36	63	63
TP53	-0.082	0.2	-9999	-0.45	63	63
RPS6KA5	-0.067	0.17	-9999	-0.37	65	65
ESR1	-0.082	0.19	-9999	-0.39	73	73
HBP1	0.01	0	-9999	-10000	0	0
MEF2C	-0.062	0.16	-9999	-0.36	63	63
MEF2A	-0.062	0.16	-9999	-0.36	63	63
EIF4EBP1	-0.068	0.18	-9999	-0.39	63	63
KRT19	-0.09	0.19	-9999	-0.36	83	83
ELK4	-0.062	0.16	-9999	-0.36	63	63
ATF6	-0.062	0.16	-9999	-0.36	63	63
ATF1	-0.068	0.18	-9999	-0.39	63	63
p38alpha-beta/MAPKAPK2	-0.055	0.17	-9999	-0.36	63	63
p38alpha-beta/MAPKAPK3	-0.055	0.17	-9999	-0.36	63	63

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	0.017	0.028	-9999	-0.26	3	3
fibroblast growth factor receptor signaling pathway	0.017	0.028	-9999	-0.26	3	3
LAMA1	-0.003	0.074	-9999	-0.44	8	8
PRNP	0.01	0	-9999	-10000	0	0
GPC1/SLIT2	-0.055	0.13	-9999	-0.31	62	62
SMAD2	0.012	0.004	-9999	-10000	0	0
GPC1/PrPc/Cu2+	0.013	0.001	-9999	-10000	0	0
GPC1/Laminin alpha1	0.005	0.051	-9999	-0.3	8	8
TDGF1	-0.23	0.22	-9999	-0.44	150	150
CRIPTO/GPC1	-0.16	0.16	-9999	-0.31	150	150
APP/GPC1	0.015	0.001	-9999	-10000	0	0
mol:NO	0	0	-9999	-10000	0	0
YES1	-0.13	0.13	-9999	-0.26	150	150
FLT1	0.007	0.037	-9999	-0.44	2	2
GPC1/TGFB/TGFBR1/TGFBR2	0.02	0.001	-9999	-10000	0	0
SERPINC1	-0.06	0.16	-9999	-0.44	44	44
FYN	-0.13	0.13	-9999	-0.26	150	150
FGR	-0.13	0.13	-9999	-0.26	150	150
positive regulation of MAPKKK cascade	-0.14	0.16	-9999	-0.3	149	149
SLIT2	-0.087	0.18	-9999	-0.44	62	62
GPC1/NRG	0.009	0.04	-9999	-0.29	5	5
NRG1	0.002	0.059	-9999	-0.44	5	5
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.018	0.023	-9999	-0.26	2	2
LYN	-0.13	0.13	-9999	-0.26	150	150
mol:Spermine	0.005	0	-9999	-10000	0	0
cell growth	0.017	0.028	-9999	-0.26	3	3
BMP signaling pathway	-0.01	0.001	-9999	-10000	0	0
SRC	-0.13	0.13	-9999	-0.26	149	149
TGFBR1	0.01	0	-9999	-10000	0	0
mol:Cu2+	0	0	-9999	-10000	0	0
PLA2G2A	0.004	0.005	-9999	-10000	0	0
GPC1	0.01	0.001	-9999	-10000	0	0
TGFBR1 (dimer)	0.01	0	-9999	-10000	0	0
VEGFA	0.01	0.001	-9999	-10000	0	0
BLK	-0.13	0.13	-9999	-0.25	150	150
HCK	-0.13	0.13	-9999	-0.25	150	150
FGF2	0.005	0.046	-9999	-0.44	3	3
FGFR1	0.01	0	-9999	-10000	0	0
VEGFR1 homodimer	0.007	0.037	-9999	-0.44	2	2
TGFBR2	0.01	0	-9999	-10000	0	0
cell death	0.014	0.001	-9999	-10000	0	0
ATIII/GPC1	-0.036	0.12	-9999	-0.31	44	44
PLA2G2A/GPC1	0.01	0.004	-9999	-10000	0	0
LCK	-0.13	0.13	-9999	-0.25	150	150
neuron differentiation	0.009	0.04	-9999	-0.29	5	5
PrPc/Cu2+	0.007	0	-9999	-10000	0	0
APP	0.01	0	-9999	-10000	0	0
TGFBR2 (dimer)	0.01	0	-9999	-10000	0	0

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.019	0.11	0.27	16	-0.26	24	40
PTK2B	0.009	0.001	-10000	0	-10000	0	0
mol:Ca2+	-0.25	0.43	-10000	0	-0.91	81	81
EDN1	0.008	0.069	0.21	15	-0.45	1	16
EDN3	0.007	0.005	-10000	0	-10000	0	0
EDN2	-0.01	0.093	-10000	0	-0.44	13	13
HRAS/GDP	-0.079	0.17	-10000	0	-0.35	66	66
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.075	0.15	0.18	4	-0.32	61	65
ADCY4	0.004	0.11	0.21	7	-0.25	36	43
ADCY5	0.005	0.11	0.21	9	-0.24	32	41
ADCY6	0.017	0.092	0.21	9	-0.23	18	27
ADCY7	0.015	0.091	0.21	9	-0.23	18	27
ADCY1	-0.076	0.14	0.21	2	-0.24	107	109
ADCY2	-0.005	0.067	-10000	0	-0.22	15	15
ADCY3	0.017	0.092	0.21	9	-0.23	18	27
ADCY8	0.01	0.089	0.2	9	-0.22	24	33
ADCY9	0.017	0.092	0.21	9	-0.22	20	29
arachidonic acid secretion	-0.14	0.26	-10000	0	-0.48	85	85
ETB receptor/Endothelin-1/Gq/GTP	-0.048	0.12	-10000	0	-0.26	55	55
GNAO1	-0.029	0.13	-10000	0	-0.44	25	25
HRAS	0.009	0.001	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	0.008	0.11	0.32	16	-0.24	24	40
ETA receptor/Endothelin-1/Gs/GTP	0.006	0.1	0.3	16	-0.23	25	41
mol:GTP	-0.004	0.007	-10000	0	-10000	0	0
COL3A1	0.01	0.13	0.28	14	-0.41	14	28
EDNRB	0.01	0.028	-10000	0	-0.44	1	1
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.008	0.15	0.3	14	-0.43	23	37
CYSLTR1	0.02	0.12	0.28	14	-0.32	12	26
SLC9A1	0.001	0.068	0.19	15	-0.2	8	23
mol:GDP	-0.086	0.18	-10000	0	-0.36	68	68
SLC9A3	-0.53	0.33	-10000	0	-0.62	240	240
RAF1	-0.1	0.21	-10000	0	-0.39	79	79
JUN	-0.13	0.25	-10000	0	-0.52	64	64
JAK2	0.019	0.11	0.27	16	-0.26	24	40
mol:IP3	-0.087	0.16	-10000	0	-0.35	66	66
ETA receptor/Endothelin-1	0.005	0.14	0.39	16	-0.32	24	40
PLCB1	-0.054	0.16	-10000	0	-0.44	40	40
PLCB2	0.006	0.006	-10000	0	-10000	0	0
ETA receptor/Endothelin-3	-0.002	0.077	0.16	12	-0.3	12	24
FOS	-0.16	0.34	-10000	0	-0.87	48	48
Gai/GDP	-0.056	0.22	-10000	0	-0.75	25	25
CRK	0.009	0.001	-10000	0	-10000	0	0
mol:Ca ++	-0.068	0.18	0.26	4	-0.38	48	52
BCAR1	0.01	0.001	-10000	0	-10000	0	0
PRKCB1	-0.084	0.16	-10000	0	-0.34	67	67
GNAQ	0.003	0.012	-10000	0	-10000	0	0
GNAZ	0.01	0	-10000	0	-10000	0	0
GNAL	0.008	0.026	-10000	0	-0.44	1	1
Gs family/GDP	-0.082	0.16	-10000	0	-0.33	67	67
ETA receptor/Endothelin-1/Gq/GTP	-0.06	0.16	0.21	4	-0.33	55	59
MAPK14	-0.063	0.12	-10000	0	-0.26	59	59
TRPC6	-0.27	0.46	-10000	0	-0.98	81	81
GNAI2	0.01	0	-10000	0	-10000	0	0
GNAI3	0.01	0	-10000	0	-10000	0	0
GNAI1	0.007	0.037	-10000	0	-0.44	2	2
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.068	0.12	-10000	0	-0.27	60	60
ETB receptor/Endothelin-2	0	0.069	-10000	0	-0.31	14	14
ETB receptor/Endothelin-3	0.012	0.02	-10000	0	-0.31	1	1
ETB receptor/Endothelin-1	0.012	0.054	0.17	6	-0.36	2	8
MAPK3	-0.15	0.31	-10000	0	-0.73	54	54
MAPK1	-0.15	0.31	-10000	0	-0.73	54	54
Rac1/GDP	-0.078	0.17	-10000	0	-0.34	66	66
cAMP biosynthetic process	-0.046	0.13	0.23	2	-0.31	34	36
MAPK8	-0.15	0.29	-10000	0	-0.57	82	82
SRC	0.009	0.001	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	0.002	0.069	-10000	0	-0.22	16	16
p130Cas/CRK/Src/PYK2	-0.13	0.24	-10000	0	-0.45	94	94
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.078	0.17	-10000	0	-0.34	66	66
COL1A2	0.016	0.1	0.28	9	-0.4	4	13
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.014	0.1	0.16	9	-0.31	24	33
mol:DAG	-0.087	0.16	-10000	0	-0.35	66	66
MAP2K2	-0.12	0.25	-10000	0	-0.52	64	64
MAP2K1	-0.12	0.25	-10000	0	-0.52	64	64
EDNRA	-0.008	0.11	0.21	15	-0.36	17	32
positive regulation of muscle contraction	0.015	0.098	0.23	15	-0.23	24	39
Gq family/GDP	-0.11	0.18	-10000	0	-0.4	63	63
HRAS/GTP	-0.089	0.18	-10000	0	-0.36	68	68
PRKCH	-0.082	0.16	-10000	0	-0.35	60	60
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCA	-0.082	0.16	-10000	0	-0.35	60	60
PRKCB	-0.081	0.16	-10000	0	-0.34	67	67
PRKCE	-0.081	0.16	-10000	0	-0.35	60	60
PRKCD	-0.082	0.16	-10000	0	-0.35	60	60
PRKCG	-0.069	0.16	0.19	1	-0.33	58	59
regulation of vascular smooth muscle contraction	-0.19	0.39	-10000	0	-1	48	48
PRKCQ	-0.087	0.17	-10000	0	-0.34	68	68
PLA2G4A	-0.16	0.29	-10000	0	-0.52	85	85
GNA14	-0.091	0.18	-10000	0	-0.45	61	61
GNA15	0.004	0.009	-10000	0	-10000	0	0
GNA12	0.01	0	-10000	0	-10000	0	0
GNA11	-0.007	0.069	-10000	0	-0.44	7	7
Rac1/GTP	0.008	0.11	0.32	16	-0.24	24	40
MMP1	-0.032	0.19	-10000	0	-0.74	18	18

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.24	0.18	-9999	-0.31	223	223
SMAD6-7/SMURF1	0.019	0.016	-9999	-0.26	1	1
NOG	0.004	0.045	-9999	-0.44	3	3
SMAD9	-0.057	0.093	-9999	-0.48	10	10
SMAD4	0.01	0	-9999	-10000	0	0
SMAD5	-0.13	0.12	-9999	-0.32	24	24
BMP7/USAG1	-0.14	0.18	-9999	-0.34	127	127
SMAD5/SKI	-0.12	0.12	-9999	-0.31	24	24
SMAD1	-0.013	0.026	-9999	-10000	0	0
BMP2	0.01	0	-9999	-10000	0	0
SMAD1/SMAD1/SMAD4	-0.015	0.016	-9999	-10000	0	0
BMPR1A	0.01	0	-9999	-10000	0	0
BMPR1B	-0.26	0.22	-9999	-0.44	172	172
BMPR1A-1B/BAMBI	-0.15	0.14	-9999	-0.26	173	173
AHSG	0.004	0.005	-9999	-10000	0	0
CER1	0.003	0.005	-9999	-10000	0	0
BMP2-4/CER1	0.016	0.003	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.11	0.11	-9999	-0.36	22	22
BMP2-4 (homodimer)	0.015	0	-9999	-10000	0	0
RGMB	0.01	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.13	0.13	-9999	-0.24	173	173
RGMA	-0.048	0.15	-9999	-0.44	37	37
SMURF1	0.01	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.12	0.11	-9999	-0.2	170	170
BMP2-4/USAG1	-0.034	0.1	-9999	-0.26	52	52
SMAD6/SMURF1/SMAD5	-0.12	0.12	-9999	-0.31	24	24
SOSTDC1	-0.073	0.17	-9999	-0.44	52	52
BMP7/BMPR2/BMPR1A-1B	-0.2	0.15	-9999	-0.28	219	219
SKI	0.01	0	-9999	-10000	0	0
BMP6 (homodimer)	0.005	0.045	-9999	-0.44	3	3
HFE2	0.007	0.004	-9999	-10000	0	0
ZFYVE16	0.01	0	-9999	-10000	0	0
MAP3K7	0.01	0	-9999	-10000	0	0
BMP2-4/CHRD	0.001	0.071	-9999	-0.26	20	20
SMAD5/SMAD5/SMAD4	-0.12	0.12	-9999	-0.31	24	24
MAPK1	0.01	0	-9999	-10000	0	0
TAK1/TAB family	-0.1	0.099	-9999	-0.3	22	22
BMP7 (homodimer)	-0.14	0.21	-9999	-0.44	93	93
NUP214	0.01	0	-9999	-10000	0	0
BMP6/FETUA	0.007	0.03	-9999	-0.28	3	3
SMAD1/SKI	-0.01	0.027	-9999	-10000	0	0
SMAD6	0.008	0.026	-9999	-0.44	1	1
CTDSP2	0.01	0	-9999	-10000	0	0
BMP2-4/FETUA	0.016	0.004	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.12	0.2	-9999	-0.44	81	81
BMPR2 (homodimer)	0.01	0	-9999	-10000	0	0
GADD34/PP1CA	0.02	0	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.18	0.16	-9999	-0.31	172	172
CHRDL1	-0.17	0.22	-9999	-0.44	115	115
ENDOFIN/SMAD1	-0.01	0.027	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.005	0.032	-9999	-0.22	1	1
SMAD6/SMURF1	0.01	0	-9999	-10000	0	0
BAMBI	0.008	0.026	-9999	-0.44	1	1
SMURF2	0.01	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.091	0.14	-9999	-0.26	115	115
BMP2-4/GREM1	-0.059	0.12	-9999	-0.26	81	81
SMAD7	0.01	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.05	0.089	-9999	-0.45	10	10
SMAD1/SMAD6	-0.01	0.027	-9999	-10000	0	0
TAK1/SMAD6	0.015	0	-9999	-10000	0	0
BMP7	-0.14	0.21	-9999	-0.44	93	93
BMP6	0.005	0.046	-9999	-0.44	3	3
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.11	0.1	-9999	-0.32	22	22
PPM1A	0.01	0	-9999	-10000	0	0
SMAD1/SMURF2	-0.01	0.027	-9999	-10000	0	0
SMAD7/SMURF1	0.015	0	-9999	-10000	0	0
CTDSPL	0.01	0	-9999	-10000	0	0
PPP1CA	0.01	0	-9999	-10000	0	0
XIAP	0.01	0	-9999	-10000	0	0
CTDSP1	0.01	0	-9999	-10000	0	0
PPP1R15A	0.01	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.19	0.2	-9999	-0.29	198	198
CHRD	-0.021	0.11	-9999	-0.44	20	20
BMPR2	0.01	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.13	0.12	-9999	-0.21	185	185
BMP4	0.01	0	-9999	-10000	0	0
FST	-0.094	0.19	-9999	-0.44	65	65
BMP2-4/NOG	0.016	0.028	-9999	-0.26	3	3
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.19	0.14	-9999	-0.26	219	219

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.013	0	-9999	-10000	0	0
ARNO/beta Arrestin1-2	0.011	0.013	-9999	-10000	0	0
EGFR	0.01	0	-9999	-10000	0	0
EPHA2	0.01	0.001	-9999	-10000	0	0
USP6	0.009	0.002	-9999	-10000	0	0
IQSEC1	0.01	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.28	0.097	-9999	-0.31	261	261
ARRB2	0.005	0.002	-9999	-10000	0	0
mol:GTP	0.01	0.004	-9999	-10000	0	0
ARRB1	0.008	0.026	-9999	-0.44	1	1
FBXO8	0.01	0	-9999	-10000	0	0
TSHR	0.008	0.004	-9999	-10000	0	0
EGF	-0.4	0.14	-9999	-0.44	261	261
somatostatin receptor activity	0	0	-9999	-0.001	116	116
ARAP2	0.01	0	-9999	-10000	0	0
mol:GDP	-0.076	0.082	-9999	-0.19	89	89
mol:PI-3-4-5-P3	0	0	-9999	0	97	97
ITGA2B	0.009	0.003	-9999	-10000	0	0
ARF6	0.01	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.025	0.001	-9999	-10000	0	0
ADAP1	0.01	0	-9999	-10000	0	0
KIF13B	0.01	0	-9999	-10000	0	0
HGF/MET	-0.005	0.07	-9999	-0.28	17	17
PXN	0.01	0	-9999	-10000	0	0
ARF6/GTP	-0.11	0.095	-9999	-0.22	113	113
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.23	0.083	-9999	-0.26	261	261
ADRB2	0.009	0.002	-9999	-10000	0	0
receptor agonist activity	0	0	-9999	0	116	116
actin filament binding	0	0	-9999	0	116	116
SRC	0.01	0.001	-9999	-10000	0	0
ITGB3	-0.012	0.096	-9999	-0.44	14	14
GNAQ	0.009	0	-9999	-10000	0	0
EFA6/PI-4-5-P2	0	0	-9999	-0.001	110	110
ARF6/GDP	-0.015	0.037	-9999	-10000	0	0
ARF6/GDP/GULP/ACAP1	-0.059	0.075	-9999	-0.21	31	31
alphaIIb/beta3 Integrin/paxillin/GIT1	0.011	0.055	-9999	-0.23	14	14
ACAP1	0.008	0.003	-9999	-10000	0	0
ACAP2	0.01	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	0.005	0.004	-9999	-10000	0	0
EFNA1	0.01	0	-9999	-10000	0	0
HGF	-0.017	0.11	-9999	-0.44	17	17
CYTH3	0.004	0	-9999	-10000	0	0
CYTH2	0.005	0.002	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	0	64	64
endosomal lumen acidification	0	0	-9999	0	116	116
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	0.01	0.001	-9999	-10000	0	0
GNAQ/ARNO	0.009	0.003	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	0	1	1
PIP3-E	0	0	-9999	0	85	85
MET	0.008	0.003	-9999	-10000	0	0
GNA14	-0.085	0.18	-9999	-0.44	61	61
GNA15	0.009	0.002	-9999	-10000	0	0
GIT1	0.01	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	113	113
GNA11	-0.001	0.069	-9999	-0.44	7	7
LHCGR	0.004	0.005	-9999	-10000	0	0
AGTR1	-0.13	0.21	-9999	-0.44	91	91
desensitization of G-protein coupled receptor protein signaling pathway	0.005	0.004	-9999	-10000	0	0
IPCEF1/ARNO	-0.17	0.063	-9999	-10000	0	0
alphaIIb/beta3 Integrin	-0.003	0.069	-9999	-0.31	14	14

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	-0.041	0.15	-10000	0	-0.37	50	50
CRKL	-0.055	0.16	-10000	0	-0.4	50	50
HRAS	-0.04	0.14	-10000	0	-0.33	50	50
mol:PIP3	-0.053	0.15	-10000	0	-0.37	50	50
SPRED1	0.01	0	-10000	0	-10000	0	0
SPRED2	0.01	0	-10000	0	-10000	0	0
GAB1	-0.059	0.17	-10000	0	-0.42	50	50
FOXO3	-0.045	0.14	-10000	0	-0.36	50	50
AKT1	-0.05	0.16	-10000	0	-0.39	50	50
BAD	-0.045	0.14	-10000	0	-0.36	50	50
megakaryocyte differentiation	-0.085	0.18	-10000	0	-0.46	50	50
GSK3B	-0.045	0.14	-10000	0	-0.36	50	50
RAF1	-0.018	0.12	-10000	0	-0.27	50	50
SHC1	0.01	0	-10000	0	-10000	0	0
STAT3	-0.059	0.17	-10000	0	-0.42	50	50
STAT1	-0.14	0.36	-10000	0	-0.93	50	50
HRAS/SPRED1	-0.018	0.12	-10000	0	-0.27	50	50
cell proliferation	-0.061	0.17	-10000	0	-0.42	50	50
PIK3CA	0.01	0	-10000	0	-10000	0	0
TEC	0.01	0	-10000	0	-10000	0	0
RPS6KB1	-0.055	0.17	-10000	0	-0.41	51	51
HRAS/SPRED2	-0.018	0.12	-10000	0	-0.27	50	50
LYN/TEC/p62DOK	-0.043	0.16	-10000	0	-0.39	50	50
MAPK3	-0.007	0.089	-10000	0	-0.2	50	50
STAP1	-0.19	0.19	-10000	0	-0.53	51	51
GRAP2	0.009	0.002	-10000	0	-10000	0	0
JAK2	-0.11	0.31	-10000	0	-0.79	50	50
STAT1 (dimer)	-0.13	0.36	-10000	0	-0.91	50	50
mol:Gleevec	0.002	0.006	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.049	0.16	-10000	0	-0.39	50	50
actin filament polymerization	-0.057	0.16	-10000	0	-0.41	50	50
LYN	0.01	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.2	0.24	-10000	0	-0.68	50	50
PIK3R1	0.01	0	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.04	0.15	-10000	0	-0.36	50	50
PI3K	-0.044	0.16	-10000	0	-0.39	51	51
PTEN	0.01	0	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.16	0.44	-10000	0	-1.1	50	50
MAPK8	-0.062	0.17	-10000	0	-0.43	50	50
STAT3 (dimer)	-0.057	0.16	-10000	0	-0.41	50	50
positive regulation of transcription	-0.004	0.075	-10000	0	-0.16	50	50
mol:GDP	-0.041	0.14	-10000	0	-0.35	50	50
PIK3C2B	-0.059	0.17	-10000	0	-0.42	50	50
CBL/CRKL	-0.046	0.15	-10000	0	-0.38	50	50
FER	-0.059	0.17	-10000	0	-0.42	50	50
SH2B3	-0.059	0.17	-10000	0	-0.42	50	50
PDPK1	-0.048	0.14	-10000	0	-0.35	50	50
SNAI2	-0.078	0.18	-10000	0	-0.45	50	50
positive regulation of cell proliferation	-0.099	0.28	-10000	0	-0.7	50	50
KITLG	0.001	0.05	-10000	0	-0.46	3	3
cell motility	-0.099	0.28	-10000	0	-0.7	50	50
PTPN6	0.012	0.009	-10000	0	-10000	0	0
EPOR	-0.025	0.11	-10000	0	-10000	0	0
STAT5A (dimer)	-0.079	0.23	-10000	0	-0.58	50	50
SOCS1	0.007	0.037	-10000	0	-0.44	2	2
cell migration	0.058	0.16	0.41	50	-10000	0	50
SOS1	0.01	0	-10000	0	-10000	0	0
EPO	0.004	0.01	-10000	0	-10000	0	0
VAV1	0.006	0.027	-10000	0	-0.44	1	1
GRB10	-0.059	0.17	-10000	0	-0.42	50	50
PTPN11	0.012	0.006	-10000	0	-10000	0	0
SCF/KIT	-0.063	0.17	-10000	0	-0.44	51	51
GO:0007205	0.003	0.009	-10000	0	-10000	0	0
MAP2K1	-0.011	0.097	-10000	0	-0.22	50	50
CBL	0.01	0	-10000	0	-10000	0	0
KIT	-0.18	0.46	-10000	0	-1.2	50	50
MAP2K2	-0.011	0.097	-10000	0	-0.22	50	50
SHC/Grb2/SOS1	-0.043	0.16	-10000	0	-0.39	50	50
STAT5A	-0.082	0.24	-10000	0	-0.6	50	50
GRB2	0.01	0	-10000	0	-10000	0	0
response to radiation	-0.076	0.18	-10000	0	-0.44	50	50
SHC/GRAP2	0.014	0.003	-10000	0	-10000	0	0
PTPRO	-0.087	0.19	-10000	0	-0.47	50	50
SH2B2	-0.059	0.17	-10000	0	-0.42	50	50
DOK1	0.01	0.001	-10000	0	-10000	0	0
MATK	-0.06	0.16	-10000	0	-0.42	50	50
CREBBP	0.001	0.043	-10000	0	-10000	0	0
BCL2	-0.023	0.11	-10000	0	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.001	0.069	-9999	-0.31	14	14
AKT1	-0.065	0.2	-9999	-0.49	53	53
PTK2B	-0.085	0.2	-9999	-0.45	65	65
VEGFR2 homodimer/Frs2	-0.094	0.24	-9999	-0.6	53	53
CAV1	0.01	0.001	-9999	-10000	0	0
CALM1	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.081	0.22	-9999	-0.55	53	53
endothelial cell proliferation	-0.057	0.19	-9999	-0.46	53	53
mol:Ca2+	-0.077	0.2	-9999	-0.51	53	53
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.071	0.21	-9999	-0.52	53	53
RP11-342D11.1	-0.082	0.2	-9999	-0.51	53	53
CDH5	0.01	0	-9999	-10000	0	0
VEGFA homodimer	0.025	0.003	-9999	-10000	0	0
SHC1	0.01	0	-9999	-10000	0	0
SHC2	0.006	0.037	-9999	-0.44	2	2
HRAS/GDP	-0.064	0.18	-9999	-0.44	53	53
SH2D2A	0.009	0.003	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.061	0.21	-9999	-0.47	55	55
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.083	0.22	-9999	-0.55	53	53
VEGFR1 homodimer	0.007	0.037	-9999	-0.44	2	2
SHC/GRB2/SOS1	-0.06	0.2	-9999	-0.48	53	53
GRB10	-0.077	0.2	-9999	-0.51	53	53
PTPN11	0.01	0	-9999	-10000	0	0
GRB2	0.01	0	-9999	-10000	0	0
PAK1	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.065	0.21	-9999	-0.5	53	53
HRAS	0.01	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	-0.05	0.14	-9999	-0.32	53	53
HIF1A	0.01	0	-9999	-10000	0	0
FRS2	0.01	0	-9999	-10000	0	0
oxygen and reactive oxygen species metabolic process	-0.071	0.21	-9999	-0.52	53	53
mol:GTP	0	0	-9999	-10000	0	0
FLT4	-0.001	0.069	-9999	-0.44	7	7
Nck/Pak	0.015	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.081	0.22	-9999	-0.55	53	53
mol:GDP	-0.063	0.19	-9999	-0.47	53	53
mol:NADP	-0.057	0.18	-9999	-0.42	55	55
eNOS/Hsp90	-0.049	0.17	-9999	-0.39	55	55
PIK3R1	0.01	0	-9999	-10000	0	0
mol:IP3	-0.078	0.2	-9999	-0.51	53	53
HIF1A/ARNT	0.015	0	-9999	-10000	0	0
SHB	0.01	0	-9999	-10000	0	0
VEGFA	0.01	0.001	-9999	-10000	0	0
VEGFC	0.01	0.001	-9999	-10000	0	0
FAK1/Vinculin	-0.086	0.23	-9999	-0.56	53	53
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.083	0.22	-9999	-0.47	65	65
PTPN6	0.01	0	-9999	-10000	0	0
EPAS1	-0.048	0.14	-9999	-0.33	53	53
mol:L-citrulline	-0.057	0.18	-9999	-0.42	55	55
ITGAV	0.01	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.071	0.21	-9999	-0.52	53	53
VEGFR2 homodimer/VEGFA homodimer	-0.078	0.22	-9999	-0.55	53	53
VEGFR2/3 heterodimer	-0.1	0.25	-9999	-0.6	56	56
VEGFB	0.01	0	-9999	-10000	0	0
MAPK11	-0.083	0.21	-9999	-0.53	53	53
VEGFR2 homodimer	-0.11	0.27	-9999	-0.68	53	53
FLT1	0.007	0.037	-9999	-0.44	2	2
NEDD4	0.01	0	-9999	-10000	0	0
MAPK3	-0.072	0.19	-9999	-0.47	53	53
MAPK1	-0.072	0.19	-9999	-0.47	53	53
VEGFA145/NRP2	0.014	0.019	-9999	-0.31	1	1
VEGFR1/2 heterodimer	-0.095	0.24	-9999	-0.61	53	53
KDR	-0.11	0.27	-9999	-0.68	53	53
VEGFA165/NRP1/VEGFR2 homodimer	-0.07	0.21	-9999	-0.5	54	54
SRC	0.01	0.001	-9999	-10000	0	0
platelet activating factor biosynthetic process	-0.074	0.19	-9999	-0.48	53	53
PI3K	-0.075	0.22	-9999	-0.55	53	53
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.081	0.22	-9999	-0.55	53	53
FES	-0.08	0.21	-9999	-0.52	53	53
GAB1	-0.082	0.23	-9999	-0.56	53	53
VEGFR2 homodimer/VEGFA homodimer/Src	-0.081	0.22	-9999	-0.55	53	53
CTNNB1	0.01	0	-9999	-10000	0	0
SOS1	0.01	0	-9999	-10000	0	0
ARNT	0.01	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.049	0.17	-9999	-0.39	55	55
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.081	0.22	-9999	-0.55	53	53
PI3K/GAB1	-0.065	0.21	-9999	-0.51	53	53
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.065	0.21	-9999	-0.5	53	53
PRKACA	0.01	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.087	0.23	-9999	-0.55	56	56
HSP90AA1	0.01	0	-9999	-10000	0	0
CDC42	-0.079	0.21	-9999	-0.52	53	53
actin cytoskeleton reorganization	-0.082	0.22	-9999	-0.55	53	53
PTK2	-0.097	0.24	-9999	-0.6	53	53
EDG1	-0.082	0.2	-9999	-0.51	53	53
mol:DAG	-0.078	0.2	-9999	-0.51	53	53
CaM/Ca2+	-0.068	0.19	-9999	-0.47	53	53
MAP2K3	-0.077	0.2	-9999	-0.5	53	53
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.071	0.21	-9999	-0.52	53	53
PLCG1	-0.079	0.21	-9999	-0.52	53	53
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.072	0.21	-9999	-0.52	53	53
IQGAP1	0.01	0	-9999	-10000	0	0
YES1	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.081	0.22	-9999	-0.55	53	53
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.081	0.22	-9999	-0.55	53	53
cell migration	-0.069	0.2	-9999	-0.5	53	53
mol:PI-3-4-5-P3	-0.069	0.21	-9999	-0.51	53	53
FYN	0.01	0	-9999	-10000	0	0
VEGFB/NRP1	-0.072	0.19	-9999	-0.48	53	53
mol:NO	-0.057	0.18	-9999	-0.42	55	55
PXN	0.01	0	-9999	-10000	0	0
HRAS/GTP	-0.081	0.17	-9999	-0.44	53	53
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.073	0.21	-9999	-0.52	53	53
VHL	0.01	0	-9999	-10000	0	0
ITGB3	-0.012	0.096	-9999	-0.44	14	14
NOS3	-0.066	0.2	-9999	-0.47	55	55
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.081	0.22	-9999	-0.53	55	55
RAC1	0.01	0	-9999	-10000	0	0
PRKCA	-0.073	0.19	-9999	-0.48	53	53
PRKCB	-0.073	0.19	-9999	-0.48	53	53
VCL	0.01	0	-9999	-10000	0	0
VEGFA165/NRP1	-0.077	0.2	-9999	-0.51	53	53
VEGFR1/2 heterodimer/VEGFA homodimer	-0.082	0.23	-9999	-0.56	53	53
VEGFA165/NRP2	0.014	0.019	-9999	-0.31	1	1
MAPKKK cascade	-0.057	0.18	-9999	-0.44	53	53
NRP2	0.008	0.026	-9999	-0.44	1	1
VEGFC homodimer	0.01	0.001	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
ROCK1	0.01	0	-9999	-10000	0	0
FAK1/Paxillin	-0.086	0.23	-9999	-0.56	53	53
MAP3K13	-0.081	0.21	-9999	-0.53	53	53
PDPK1	-0.061	0.19	-9999	-0.45	53	53

×

FOXM1 transcription factor network

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
NFATC3	0.22	0.32	0.79	37	-0.97	1	38
PLK1	0.075	0.13	0.4	30	-10000	0	30
BIRC5	0.099	0.14	0.45	9	-10000	0	9
HSPA1B	0.22	0.32	0.78	38	-0.97	1	39
MAP2K1	0.056	0.067	0.2	40	-10000	0	40
BRCA2	0.22	0.33	0.79	40	-0.97	1	41
FOXM1	0.18	0.35	0.9	32	-0.8	6	38
XRCC1	0.22	0.32	0.78	38	-0.97	1	39
FOXM1B/p19	-0.031	0.14	-10000	0	-0.86	2	2
Cyclin D1/CDK4	0.2	0.3	0.69	39	-0.9	2	41
CDC2	0.23	0.34	0.8	46	-0.73	6	52
TGFA	0.2	0.3	0.72	38	-0.76	2	40
SKP2	0.22	0.32	0.78	38	-0.97	1	39
CCNE1	0.017	0.013	-10000	0	-10000	0	0
CKS1B	0.22	0.32	0.78	39	-0.97	1	40
RB1	-0.024	0.06	-10000	0	-10000	0	0
FOXM1C/SP1	0.2	0.31	0.71	38	-0.75	6	44
AURKB	0.12	0.14	0.39	33	-10000	0	33
CENPF	0.23	0.34	0.84	40	-0.97	1	41
CDK4	0.026	0.026	-10000	0	-10000	0	0
MYC	0.2	0.29	0.7	38	-0.86	1	39
CHEK2	0.055	0.066	0.2	35	-10000	0	35
ONECUT1	0.2	0.31	0.72	37	-0.82	2	39
CDKN2A	-0.004	0.023	-10000	0	-0.13	6	6
LAMA4	0.23	0.33	0.8	37	-0.97	1	38
FOXM1B/HNF6	0.2	0.32	0.73	36	-0.93	2	38
FOS	0.11	0.49	0.78	39	-1	32	71
SP1	0.011	0.001	-10000	0	-10000	0	0
CDC25B	0.22	0.33	0.78	39	-0.97	1	40
response to radiation	0.04	0.054	0.15	45	-10000	0	45
CENPB	0.22	0.32	0.78	39	-0.97	1	40
CENPA	0.24	0.35	0.82	46	-0.97	1	47
NEK2	0.24	0.35	0.82	46	-0.97	1	47
HIST1H2BA	0.22	0.32	0.77	39	-0.97	1	40
CCNA2	0.014	0.012	-10000	0	-10000	0	0
EP300	0.01	0	-10000	0	-10000	0	0
CCNB1/CDK1	0.21	0.34	0.82	39	-1.1	1	40
CCNB2	0.24	0.35	0.82	45	-0.97	1	46
CCNB1	0.23	0.35	0.84	39	-1	1	40
ETV5	0.22	0.32	0.79	36	-0.97	1	37
ESR1	0.18	0.41	0.79	36	-1.1	13	49
CCND1	0.21	0.32	0.74	39	-0.93	2	41
GSK3A	0.049	0.056	0.17	34	-10000	0	34
Cyclin A-E1/CDK1-2	0.04	0.044	0.18	9	-10000	0	9
CDK2	0.02	0.015	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.048	0.066	0.17	52	-10000	0	52
FOXM1B/Cbp/p300	0.026	0.18	-10000	0	-0.73	6	6
GAS1	0.18	0.42	0.78	38	-1	15	53
MMP2	0.22	0.33	0.78	39	-1.1	2	41
RB1/FOXM1C	0.2	0.3	0.71	37	-0.9	2	39
CREBBP	0.01	0	-10000	0	-10000	0	0

×

HIF-1-alpha transcription factor network

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
PKM2	0.19	0.27	0.6	42	-0.73	3	45
HDAC7	0.012	0.007	-10000	0	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	0.052	0.16	-10000	0	-0.56	3	3
SMAD4	0.01	0	-10000	0	-10000	0	0
ID2	0.19	0.27	0.6	42	-0.73	3	45
AP1	-0.033	0.12	-10000	0	-0.31	44	44
ABCG2	0.19	0.27	0.6	42	-0.73	3	45
HIF1A	0.055	0.067	0.19	12	-10000	0	12
TFF3	0.16	0.31	0.6	40	-0.8	5	45
GATA2	-0.082	0.18	-10000	0	-0.44	60	60
AKT1	0.068	0.074	0.19	43	-10000	0	43
response to hypoxia	0.042	0.068	0.15	47	-0.12	3	50
MCL1	0.19	0.27	0.6	42	-0.73	3	45
NDRG1	0.19	0.27	0.6	42	-0.73	3	45
SERPINE1	0.18	0.29	0.6	40	-0.79	6	46
FECH	0.19	0.27	0.6	42	-0.73	3	45
FURIN	0.19	0.27	0.6	42	-0.73	3	45
NCOA2	-0.029	0.13	-10000	0	-0.44	26	26
EP300	0.12	0.12	0.3	64	-10000	0	64
HMOX1	0.16	0.26	0.59	27	-0.7	4	31
BHLHE40	0.19	0.27	0.6	42	-0.73	3	45
BHLHE41	0.15	0.26	0.59	31	-0.73	3	34
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.046	0.073	-10000	0	-10000	0	0
ENG	0.1	0.095	0.26	41	-10000	0	41
JUN	0.01	0.003	-10000	0	-10000	0	0
RORA	0.19	0.27	0.6	42	-0.73	3	45
ABCB1	-0.036	0.16	-10000	0	-0.79	11	11
TFRC	0.19	0.27	0.6	42	-0.73	3	45
CXCR4	0.16	0.26	0.59	30	-0.73	3	33
TF	0.18	0.27	0.6	41	-0.73	3	44
CITED2	0.19	0.27	0.6	42	-0.73	3	45
HIF1A/ARNT	0.03	0.18	-10000	0	-0.8	3	3
LDHA	-0.005	0.017	-10000	0	-10000	0	0
ETS1	0.19	0.27	0.6	42	-0.73	3	45
PGK1	0.19	0.27	0.6	42	-0.73	3	45
NOS2	0.18	0.29	0.6	42	-0.82	5	47
ITGB2	0.12	0.24	0.58	20	-0.73	3	23
ALDOA	0.19	0.27	0.6	42	-0.73	3	45
Cbp/p300/CITED2	0.15	0.24	0.53	23	-0.72	3	26
FOS	-0.058	0.16	-10000	0	-0.44	44	44
HK2	0.03	0.17	0.58	3	-0.73	3	6
SP1	0.004	0.043	-10000	0	-0.19	12	12
GCK	0.15	0.16	0.47	20	-10000	0	20
HK1	0.19	0.27	0.6	42	-0.73	3	45
NPM1	0.19	0.27	0.6	42	-0.73	3	45
EGLN1	0.19	0.27	0.6	42	-0.73	3	45
CREB1	0.013	0	-10000	0	-10000	0	0
PGM1	0.19	0.27	0.6	42	-0.73	3	45
SMAD3	0.01	0	-10000	0	-10000	0	0
EDN1	0.037	0.22	0.52	3	-0.56	15	18
IGFBP1	0.17	0.28	0.6	38	-0.7	5	43
VEGFA	0.21	0.22	0.52	42	-0.52	2	44
HIF1A/JAB1	0.011	0.027	-10000	0	-10000	0	0
CP	0.15	0.28	0.59	29	-0.7	6	35
CXCL12	0.18	0.3	0.6	42	-0.72	9	51
COPS5	0.011	0.002	-10000	0	-10000	0	0
SMAD3/SMAD4	0.015	0	-10000	0	-10000	0	0
BNIP3	0.19	0.27	0.6	42	-0.73	3	45
EGLN3	0.17	0.26	0.59	34	-0.73	3	37
CA9	0.039	0.17	0.58	3	-0.68	3	6
TERT	0.14	0.25	0.58	27	-0.7	3	30
ENO1	0.19	0.27	0.6	42	-0.73	3	45
PFKL	0.19	0.27	0.6	42	-0.73	3	45
NCOA1	0.01	0.001	-10000	0	-10000	0	0
ADM	0.19	0.27	0.6	41	-0.73	3	44
ARNT	0.055	0.067	0.19	12	-10000	0	12
HNF4A	-0.036	0.14	-10000	0	-0.44	31	31
ADFP	0.17	0.26	0.57	36	-0.73	3	39
SLC2A1	0.2	0.21	0.51	38	-0.52	2	40
LEP	0.14	0.25	0.57	25	-0.73	3	28
HIF1A/ARNT/Cbp/p300	0.075	0.18	-10000	0	-0.58	3	3
EPO	0.17	0.23	0.54	19	-0.85	1	20
CREBBP	0.12	0.12	0.32	51	-10000	0	51
HIF1A/ARNT/Cbp/p300/HDAC7	0.077	0.18	-10000	0	-0.56	3	3
PFKFB3	0.19	0.27	0.6	42	-0.73	3	45
NT5E	0.19	0.28	0.6	42	-0.79	3	45

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.045	0.12	-9999	-0.31	53	53
alphaV beta3 Integrin	0.003	0.065	-9999	-0.26	17	17
PTK2	-0.1	0.17	-9999	-0.35	72	72
IGF1R	0.01	0	-9999	-10000	0	0
PI4KB	0.01	0	-9999	-10000	0	0
MFGE8	0.01	0	-9999	-10000	0	0
SRC	0.01	0.001	-9999	-10000	0	0
CDKN1B	-0.1	0.18	-9999	-0.41	74	74
VEGFA	0.01	0.001	-9999	-10000	0	0
ILK	-0.1	0.18	-9999	-0.41	74	74
ROCK1	0.01	0	-9999	-10000	0	0
AKT1	-0.092	0.17	-9999	-0.38	74	74
PTK2B	-0.037	0.1	-9999	-0.22	65	65
alphaV/beta3 Integrin/JAM-A	-0.05	0.11	-9999	-0.22	83	83
CBL	0.01	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.18	0.14	-9999	-0.26	200	200
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.016	0.049	-9999	-0.23	11	11
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.084	0.14	-9999	-0.24	114	114
alphaV/beta3 Integrin/Syndecan-1	0.005	0.061	-9999	-0.25	15	15
PI4KA	0.01	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0	0.066	-9999	-0.2	26	26
PI4 Kinase	0.015	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	0.003	0.065	-9999	-0.26	17	17
RPS6KB1	0.002	0.066	-9999	-0.19	26	26
TLN1	0.01	0	-9999	-10000	0	0
MAPK3	-0.039	0.11	-9999	-0.4	17	17
GPR124	0.008	0.026	-9999	-0.44	1	1
MAPK1	-0.039	0.11	-9999	-0.4	17	17
PXN	0.01	0	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.008	0.09	-9999	-0.29	26	26
cell adhesion	-0.15	0.12	-9999	-0.23	196	196
ANGPTL3	-0.29	0.21	-9999	-0.44	193	193
VEGFR2 homodimer/VEGFA homodimer/Src	-0.031	0.11	-9999	-0.26	53	53
IGF-1R heterotetramer	0.01	0	-9999	-10000	0	0
Rac1/GDP	0.007	0	-9999	-10000	0	0
TGFBR2	0.01	0	-9999	-10000	0	0
ITGB3	-0.012	0.096	-9999	-0.44	14	14
IGF1	0	0.064	-9999	-0.44	6	6
RAC1	0.01	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	0.005	0.061	-9999	-0.26	15	15
apoptosis	0.01	0	-9999	-10000	0	0
CD47	0.01	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	0.006	0.06	-9999	-0.26	14	14
VCL	0.01	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.032	0.12	-9999	-0.28	50	50
CSF1	0.007	0.037	-9999	-0.44	2	2
PIK3C2A	-0.1	0.18	-9999	-0.41	74	74
PI4 Kinase/Pyk2	-0.082	0.13	-9999	-0.22	116	116
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.034	0.11	-9999	-0.24	65	65
FAK1/Vinculin	-0.083	0.14	-9999	-0.29	72	72
alphaV beta3/Integrin/ppsTEM5	0.005	0.062	-9999	-0.26	15	15
RHOA	0.01	0	-9999	-10000	0	0
VTN	-0.11	0.2	-9999	-0.44	74	74
BCAR1	0.01	0	-9999	-10000	0	0
FGF2	0.005	0.046	-9999	-0.44	3	3
F11R	0.006	0.032	-9999	-0.31	3	3
alphaV/beta3 Integrin/Lactadherin	0.006	0.06	-9999	-0.26	14	14
alphaV/beta3 Integrin/TGFBR2	0.006	0.06	-9999	-0.26	14	14
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.023	0.021	-9999	-0.23	2	2
HSP90AA1	0.01	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	0.006	0.054	-9999	-0.23	14	14
mol:GDP	0	0	-9999	-10000	0	0
FN1	0.009	0.003	-9999	-10000	0	0
alphaV/beta3 Integrin/Pyk2	-0.033	0.1	-9999	-0.22	65	65
SDC1	0.008	0.026	-9999	-0.44	1	1
VAV3	0.011	0.024	-9999	-0.22	3	3
PTPN11	0.01	0	-9999	-10000	0	0
IRS1	0.002	0.059	-9999	-0.44	5	5
FAK1/Paxillin	-0.083	0.14	-9999	-0.29	72	72
cell migration	-0.075	0.13	-9999	-0.26	72	72
ITGAV	0.01	0	-9999	-10000	0	0
PI3K	-0.042	0.11	-9999	-0.2	83	83
SPP1	0.005	0.046	-9999	-0.44	3	3
KDR	-0.072	0.17	-9999	-0.44	53	53
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.01	0	-9999	-10000	0	0
COL4A3	-0.013	0.1	-9999	-0.44	15	15
angiogenesis	-0.058	0.13	-9999	-0.42	18	18
Rac1/GTP	0.016	0.022	-9999	-0.2	3	3
EDIL3	-0.053	0.16	-9999	-0.44	40	40
cell proliferation	0.006	0.059	-9999	-0.26	14	14

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.38	0.48	0.65	1	-1.2	51	52
STAT6 (cleaved dimer)	-0.41	0.42	-10000	0	-0.96	87	87
IGHG1	-0.12	0.18	0.42	5	-0.36	19	24
IGHG3	-0.37	0.46	0.56	2	-0.93	88	90
AKT1	-0.15	0.23	0.48	3	-0.5	16	19
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.1	0.18	0.44	3	-0.44	1	4
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.16	0.23	0.46	4	-0.5	21	25
THY1	-0.61	0.7	0.65	1	-1.4	112	113
MYB	0.007	0.004	-10000	0	-10000	0	0
HMGA1	0.01	0.001	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.19	0.28	0.53	6	-0.56	47	53
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.16	0.23	0.46	4	-0.5	19	23
SP1	0.015	0.012	-10000	0	-10000	0	0
INPP5D	0.009	0.002	-10000	0	-10000	0	0
SOCS5	0.017	0.021	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.36	0.48	0.54	3	-1.1	55	58
SOCS1	-0.24	0.32	0.5	3	-0.72	52	55
SOCS3	-0.16	0.25	0.49	3	-1.3	1	4
FCER2	-0.27	0.37	0.65	4	-0.8	52	56
PARP14	0.011	0.006	-10000	0	-10000	0	0
CCL17	-0.36	0.49	0.68	2	-1.2	50	52
GRB2	0.01	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.13	0.2	0.42	5	-0.41	10	15
T cell proliferation	-0.36	0.48	0.59	2	-1.2	51	53
IL4R/JAK1	-0.38	0.48	-10000	0	-1.1	52	52
EGR2	-0.43	0.58	0.69	2	-1.4	60	62
JAK2	-0.017	0.042	0.15	2	-10000	0	2
JAK3	0.012	0.007	-10000	0	-10000	0	0
PIK3R1	0.01	0	-10000	0	-10000	0	0
JAK1	0.008	0.017	-10000	0	-10000	0	0
COL1A2	-0.11	0.17	0.45	2	-10000	0	2
CCL26	-0.38	0.48	0.68	2	-1.2	51	53
IL4R	-0.4	0.51	0.72	2	-1.2	52	54
PTPN6	0.018	0.016	-10000	0	-10000	0	0
IL13RA2	-0.74	0.66	0.65	1	-1.3	161	162
IL13RA1	-0.017	0.042	0.15	2	-10000	0	2
IRF4	-0.046	0.15	0.49	1	-1.3	1	2
ARG1	-0.078	0.15	0.47	2	-10000	0	2
CBL	-0.18	0.26	0.49	5	-0.53	47	52
GTF3A	0.019	0.019	-10000	0	-10000	0	0
PIK3CA	0.01	0	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.018	0.062	0.2	5	-10000	0	5
IRF4/BCL6	-0.053	0.12	-10000	0	-1.2	1	1
CD40LG	0.016	0.017	-10000	0	-10000	0	0
MAPK14	-0.18	0.26	0.49	5	-0.55	36	41
mitosis	-0.14	0.23	0.45	4	-0.48	16	20
STAT6	-0.42	0.56	0.76	3	-1.2	67	70
SPI1	0.01	0.009	-10000	0	-10000	0	0
RPS6KB1	-0.14	0.22	0.46	3	-0.47	9	12
STAT6 (dimer)	-0.42	0.56	0.76	3	-1.2	67	70
STAT6 (dimer)/PARP14	-0.4	0.51	0.59	2	-1.1	68	70
mast cell activation	0.008	0.016	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.15	0.23	0.46	5	-0.5	11	16
FRAP1	-0.15	0.23	0.48	3	-0.5	16	19
LTA	-0.37	0.49	0.7	3	-1.2	51	54
FES	0.008	0.026	-10000	0	-0.44	1	1
T-helper 1 cell differentiation	0.41	0.55	1.1	75	-0.73	4	79
CCL11	-0.47	0.57	-10000	0	-1.2	81	81
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.15	0.22	0.46	4	-0.49	12	16
IL2RG	0.014	0.006	-10000	0	-10000	0	0
IL10	-0.37	0.48	0.73	2	-1.1	52	54
IRS1	0.002	0.059	-10000	0	-0.44	5	5
IRS2	0.01	0.001	-10000	0	-10000	0	0
IL4	-0.083	0.14	0.43	3	-10000	0	3
IL5	-0.38	0.48	0.64	1	-1.2	51	52
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.3	0.39	0.62	4	-0.86	53	57
COL1A1	-0.11	0.2	0.5	5	-10000	0	5
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.39	0.48	-10000	0	-1.2	51	51
IL2R gamma/JAK3	0.014	0.01	-10000	0	-10000	0	0
TFF3	-0.48	0.61	0.64	2	-1.4	75	77
ALOX15	-0.38	0.48	0.65	1	-1.2	50	51
MYBL1	0.009	0.002	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.3	0.38	0.56	4	-0.87	53	57
SHC1	0.01	0	-10000	0	-10000	0	0
CEBPB	0.012	0.008	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.15	0.23	0.45	4	-0.48	19	23
mol:PI-3-4-5-P3	-0.15	0.23	0.48	3	-0.5	16	19
PI3K	-0.15	0.24	0.48	3	-0.52	16	19
DOK2	0.008	0.026	-10000	0	-0.44	1	1
ETS1	0.015	0.022	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.12	0.19	0.4	5	-0.39	6	11
ITGB3	-0.41	0.52	0.65	1	-1.2	60	61
PIGR	-0.4	0.51	0.74	1	-1.2	59	60
IGHE	0.031	0.045	0.12	1	-0.14	3	4
MAPKKK cascade	-0.11	0.19	0.4	5	-0.38	6	11
BCL6	0.008	0.005	-10000	0	-10000	0	0
OPRM1	-0.38	0.48	0.64	1	-1.2	50	51
RETNLB	-0.38	0.48	-10000	0	-1.2	50	50
SELP	-0.43	0.56	0.65	1	-1.4	55	56
AICDA	-0.35	0.46	0.64	1	-1.1	51	52

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	0.016	0.016	-10000	0	-10000	0	0
NFATC2	0.002	0.16	-10000	0	-0.44	17	17
NFATC3	-0.019	0.11	-10000	0	-0.26	45	45
CD40LG	-0.094	0.4	0.43	3	-0.91	48	51
ITCH	0.012	0.037	-10000	0	-0.22	7	7
CBLB	0.012	0.037	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.075	0.21	-10000	0	-0.58	25	25
JUNB	0.01	0	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0.015	0.045	-10000	0	-0.27	7	7
T cell anergy	-0.002	0.061	-10000	0	-0.36	7	7
TLE4	0.014	0.11	-10000	0	-0.4	5	5
Jun/NFAT1-c-4/p21SNFT	-0.1	0.38	-10000	0	-0.88	50	50
AP-1/NFAT1-c-4	-0.15	0.45	0.43	1	-1.1	49	50
IKZF1	0.01	0.11	0.27	1	-0.4	5	6
T-helper 2 cell differentiation	-0.35	0.31	-10000	0	-0.7	87	87
AP-1/NFAT1	-0.029	0.16	0.23	2	-0.35	42	44
CALM1	0.012	0.027	-10000	0	-0.16	7	7
EGR2	-0.13	0.52	0.46	1	-1.2	49	50
EGR3	-0.16	0.55	0.46	1	-1.3	49	50
NFAT1/FOXP3	0.004	0.11	-10000	0	-0.4	5	5
EGR1	-0.024	0.12	-10000	0	-0.44	23	23
JUN	0.017	0.02	-10000	0	-10000	0	0
EGR4	0.007	0.008	-10000	0	-10000	0	0
mol:Ca2+	0.002	0.026	-10000	0	-0.16	7	7
GBP3	0.014	0.11	-10000	0	-0.4	5	5
FOSL1	0.007	0.037	-10000	0	-0.44	2	2
NFAT1-c-4/MAF/IRF4	-0.1	0.37	-10000	0	-0.87	50	50
DGKA	0.01	0.11	-10000	0	-0.4	5	5
CREM	0.01	0.002	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.11	0.38	-10000	0	-0.9	50	50
CTLA4	-0.001	0.082	-10000	0	-0.33	5	5
NFAT1-c-4 (dimer)/EGR1	-0.12	0.41	-10000	0	-0.97	50	50
NFAT1-c-4 (dimer)/EGR4	-0.11	0.38	-10000	0	-0.91	50	50
FOS	-0.052	0.17	-10000	0	-0.44	44	44
IFNG	-0.039	0.14	-10000	0	-0.55	6	6
T cell activation	-0.037	0.24	0.41	1	-0.62	27	28
MAF	0.01	0	-10000	0	-10000	0	0
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.061	0.31	0.71	50	-0.43	1	51
TNF	-0.099	0.37	-10000	0	-0.86	51	51
FASLG	-0.15	0.56	-10000	0	-1.3	50	50
TBX21	0.014	0.013	-10000	0	-10000	0	0
BATF3	0.01	0.001	-10000	0	-10000	0	0
PRKCQ	0.002	0.075	-10000	0	-0.44	8	8
PTPN1	0.014	0.11	-10000	0	-0.4	5	5
NFAT1-c-4/ICER1	-0.11	0.38	-10000	0	-0.9	50	50
GATA3	-0.34	0.19	-10000	0	-0.44	225	225
T-helper 1 cell differentiation	-0.034	0.14	-10000	0	-0.54	6	6
IL2RA	-0.076	0.21	-10000	0	-0.55	33	33
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	0.013	0.11	-10000	0	-0.4	5	5
E2F1	0.009	0.006	-10000	0	-10000	0	0
PPARG	0.01	0.001	-10000	0	-10000	0	0
SLC3A2	0.014	0.11	-10000	0	-0.4	5	5
IRF4	0.008	0.026	-10000	0	-0.44	1	1
PTGS2	-0.12	0.46	0.47	7	-0.96	55	62
CSF2	-0.094	0.41	0.49	5	-0.9	49	54
JunB/Fra1/NFAT1-c-4	-0.099	0.37	-10000	0	-0.87	50	50
IL4	-0.37	0.33	-10000	0	-0.74	86	86
IL5	-0.09	0.41	0.46	7	-0.91	48	55
IL2	-0.038	0.24	0.41	1	-0.63	26	27
IL3	-0.03	0.053	-10000	0	-10000	0	0
RNF128	0.004	0.085	-10000	0	-0.54	7	7
NFATC1	-0.062	0.31	0.43	1	-0.71	50	51
CDK4	0.044	0.21	0.53	28	-10000	0	28
PTPRK	0.014	0.11	-10000	0	-0.4	5	5
IL8	-0.14	0.38	0.42	1	-0.9	49	50
POU2F1	0.01	0	-10000	0	-10000	0	0

×

amb2 Integrin signaling

Figure S19. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S19. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	0.01	0.029	-10000	0	-0.26	1	1
alphaM/beta2 Integrin/GPIbA	0.01	0.025	-10000	0	-10000	0	0
alphaM/beta2 Integrin/proMMP-9	0.002	0.037	-10000	0	-0.26	4	4
PLAUR	0.009	0.002	-10000	0	-10000	0	0
HMGB1	0.006	0.019	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Talin	0.011	0.024	-10000	0	-10000	0	0
AGER	0.005	0.018	-10000	0	-10000	0	0
RAP1A	0.01	0	-10000	0	-10000	0	0
SELPLG	0.009	0.003	-10000	0	-10000	0	0
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	0.001	0.061	-10000	0	-0.18	25	25
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	0	0.052	-10000	0	-0.44	4	4
CYR61	-0.004	0.078	-10000	0	-0.44	9	9
TLN1	0.01	0	-10000	0	-10000	0	0
Rap1/GTP	-0.1	0.1	-10000	0	-0.33	33	33
RHOA	0.01	0	-10000	0	-10000	0	0
P-selectin oligomer	-0.034	0.13	-10000	0	-0.44	28	28
MYH2	-0.15	0.14	-10000	0	-0.4	44	44
MST1R	0.006	0.037	-10000	0	-0.44	2	2
leukocyte activation during inflammatory response	-0.012	0.07	-10000	0	-0.22	26	26
APOB	-0.015	0.099	-10000	0	-0.44	15	15
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	0.008	0.026	-10000	0	-0.44	1	1
JAM3	0.008	0.026	-10000	0	-0.44	1	1
GP1BA	0.008	0.026	-10000	0	-0.44	1	1
alphaM/beta2 Integrin/CTGF	0.004	0.047	-10000	0	-0.25	7	7
alphaM/beta2 Integrin	-0.12	0.12	-10000	0	-0.33	44	44
JAM3 homodimer	0.008	0.026	-10000	0	-0.44	1	1
ICAM2	0.01	0	-10000	0	-10000	0	0
ICAM1	0.01	0.001	-10000	0	-10000	0	0
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.12	0.12	-10000	0	-0.33	44	44
cell adhesion	0.01	0.025	-10000	0	-10000	0	0
NFKB1	0.007	0.12	0.22	1	-0.32	28	29
THY1	-0.15	0.22	-10000	0	-0.44	105	105
RhoA/GDP	0.007	0	-10000	0	-10000	0	0
Lipoprotein(a)	-0.019	0.081	-10000	0	-0.26	29	29
alphaM/beta2 Integrin/LRP/tPA	-0.008	0.075	-10000	0	-0.23	27	27
IL6	-0.022	0.22	0.27	2	-0.62	31	33
ITGB2	0.004	0.018	-10000	0	-10000	0	0
elevation of cytosolic calcium ion concentration	0.008	0.046	-10000	0	-0.24	7	7
alphaM/beta2 Integrin/JAM2/JAM3	0.011	0.041	-10000	0	-0.24	5	5
JAM2	0.004	0.052	-10000	0	-0.44	4	4
alphaM/beta2 Integrin/ICAM1	0.013	0.035	-10000	0	-0.23	3	3
alphaM/beta2 Integrin/uPA/Plg	-0.12	0.12	-10000	0	-0.23	151	151
RhoA/GTP	-0.16	0.15	-10000	0	-0.27	133	133
positive regulation of phagocytosis	-0.074	0.087	-10000	0	-0.26	32	32
Ron/MSP	0.01	0.033	-10000	0	-0.31	3	3
alphaM/beta2 Integrin/uPAR/uPA	0.009	0.047	-10000	0	-0.24	7	7
alphaM/beta2 Integrin/uPAR	0.011	0.024	-10000	0	-10000	0	0
PLAU	-0.001	0.069	-10000	0	-0.44	7	7
PLAT	-0.035	0.14	-10000	0	-0.44	29	29
actin filament polymerization	-0.14	0.14	-10000	0	-0.38	44	44
MST1	0.008	0.026	-10000	0	-0.44	1	1
alphaM/beta2 Integrin/lipoprotein(a)	-0.011	0.071	-10000	0	-0.22	26	26
TNF	0.009	0.12	-10000	0	-0.33	26	26
RAP1B	0.01	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPA	0.004	0.05	-10000	0	-0.27	7	7
fibrinolysis	-0.12	0.12	-10000	0	-0.23	151	151
HCK	0.007	0.026	-10000	0	-0.44	1	1
dendritic cell antigen processing and presentation	-0.12	0.12	-10000	0	-0.33	44	44
VTN	-0.11	0.2	-10000	0	-0.44	74	74
alphaM/beta2 Integrin/CYR61	0.003	0.05	-10000	0	-0.25	8	8
LPA	-0.018	0.095	-10000	0	-0.44	14	14
LRP1	0.01	0	-10000	0	-10000	0	0
cell migration	0.002	0.037	-10000	0	-0.23	5	5
FN1	0.009	0.003	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Thy1	-0.084	0.13	-10000	0	-0.26	101	101
MPO	0.009	0.003	-10000	0	-10000	0	0
KNG1	-0.26	0.22	-10000	0	-0.44	169	169
RAP1/GDP	0.013	0	-10000	0	-10000	0	0
ROCK1	-0.15	0.14	-10000	0	-0.42	40	40
ELA2	0	0	-10000	0	-10000	0	0
PLG	-0.25	0.22	-10000	0	-0.44	164	164
CTGF	-0.001	0.069	-10000	0	-0.44	7	7
alphaM/beta2 Integrin/Hck	0.01	0.03	-10000	0	-0.31	1	1
ITGAM	0.005	0.018	-10000	0	-10000	0	0
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.009	0.078	-10000	0	-0.24	28	28
HP	0.007	0.004	-10000	0	-10000	0	0
leukocyte adhesion	-0.081	0.13	-10000	0	-0.25	89	89
SELP	-0.034	0.13	-10000	0	-0.44	28	28

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.048	0.12	-9999	-0.31	53	53
PDGFRB	-0.007	0.083	-9999	-0.44	10	10
SPHK1	-0.01	0.028	-9999	-10000	0	0
mol:S1P	-0.014	0.037	-9999	-10000	0	0
S1P1/S1P/Gi	-0.077	0.18	-9999	-0.39	63	63
GNAO1	-0.032	0.13	-9999	-0.45	25	25
PDGFB-D/PDGFRB/PLCgamma1	-0.078	0.16	-9999	-0.35	64	64
PLCG1	-0.069	0.17	-9999	-0.37	62	62
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.007	0.083	-9999	-0.44	10	10
GNAI2	0.007	0.009	-9999	-10000	0	0
GNAI3	0.007	0.008	-9999	-10000	0	0
GNAI1	0.004	0.038	-9999	-0.44	2	2
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.046	0.1	-9999	-0.26	53	53
S1P1/S1P	-0.042	0.099	-9999	-0.25	29	29
negative regulation of cAMP metabolic process	-0.075	0.18	-9999	-0.38	63	63
MAPK3	-0.1	0.24	-9999	-0.56	58	58
calcium-dependent phospholipase C activity	-0.002	0.003	-9999	-10000	0	0
Rac1/GDP	0.007	0	-9999	-10000	0	0
RhoA/GDP	0.007	0	-9999	-10000	0	0
KDR	-0.075	0.17	-9999	-0.44	53	53
PLCB2	-0.037	0.09	-9999	-0.24	22	22
RAC1	0.01	0	-9999	-10000	0	0
RhoA/GTP	-0.045	0.081	-9999	-0.23	22	22
receptor internalization	-0.049	0.088	-9999	-0.23	29	29
PTGS2	-0.17	0.38	-9999	-0.99	50	50
Rac1/GTP	-0.045	0.081	-9999	-0.22	28	28
RHOA	0.01	0	-9999	-10000	0	0
VEGFA	0.008	0.006	-9999	-10000	0	0
negative regulation of T cell proliferation	-0.075	0.18	-9999	-0.38	63	63
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.007	0.008	-9999	-10000	0	0
MAPK1	-0.1	0.24	-9999	-0.56	58	58
S1P1/S1P/PDGFB-D/PDGFRB	-0.059	0.11	-9999	-0.29	29	29
ABCC1	0.007	0.007	-9999	-10000	0	0

×

Signaling events mediated by PTP1B

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
PDGFRB	-0.006	0.082	-10000	0	-0.44	10	10
Jak2/Leptin Receptor	-0.12	0.12	-10000	0	-0.27	111	111
PTP1B/AKT1	-0.062	0.054	-10000	0	-0.22	22	22
FYN	0.01	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.072	0.06	-10000	0	-0.25	22	22
EGFR	-0.009	0.006	-10000	0	-10000	0	0
EGF/EGFR	-0.23	0.079	-10000	0	-0.25	265	265
CSF1	0.007	0.037	-10000	0	-0.44	2	2
AKT1	0.01	0	-10000	0	-10000	0	0
INSR	0.01	0	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.076	0.08	-10000	0	-0.29	30	30
Insulin Receptor/Insulin	-0.044	0.043	-10000	0	-0.2	5	5
HCK	0.007	0.026	-10000	0	-0.44	1	1
CRK	0.01	0	-10000	0	-10000	0	0
TYK2	-0.067	0.057	-10000	0	-0.24	22	22
EGF	-0.4	0.14	-10000	0	-0.45	261	261
YES1	0.01	0	-10000	0	-10000	0	0
CAV1	-0.14	0.058	-10000	0	-0.25	32	32
TXN	0.004	0.002	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.066	0.064	-10000	0	-0.24	26	26
cell migration	0.072	0.06	0.25	22	-10000	0	22
STAT3	0.009	0	-10000	0	-10000	0	0
PRLR	-0.16	0.22	-10000	0	-0.44	111	111
ITGA2B	0.008	0.003	-10000	0	-10000	0	0
CSF1R	0.008	0.026	-10000	0	-0.44	1	1
Prolactin Receptor/Prolactin	-0.12	0.16	-10000	0	-0.31	111	111
FGR	0.008	0.026	-10000	0	-0.44	1	1
PTP1B/p130 Cas	-0.067	0.057	-10000	0	-0.24	22	22
Crk/p130 Cas	-0.062	0.056	-10000	0	-0.23	22	22
DOK1	-0.061	0.062	-10000	0	-0.23	25	25
JAK2	-0.13	0.13	-10000	0	-0.29	112	112
Jak2/Leptin Receptor/Leptin	-0.071	0.066	-10000	0	-0.27	11	11
PIK3R1	0.01	0	-10000	0	-10000	0	0
PTPN1	-0.072	0.06	-10000	0	-0.25	22	22
LYN	0.01	0	-10000	0	-10000	0	0
CDH2	-0.01	0.093	-10000	0	-0.44	13	13
SRC	-0.02	0.023	-10000	0	-10000	0	0
ITGB3	-0.013	0.097	-10000	0	-0.44	14	14
CAT1/PTP1B	-0.16	0.089	-10000	0	-0.33	22	22
CAPN1	0.008	0.001	-10000	0	-10000	0	0
CSK	0.01	0	-10000	0	-10000	0	0
PI3K	-0.039	0.041	-10000	0	-0.24	1	1
mol:H2O2	-0.004	0.003	-10000	0	-10000	0	0
STAT3 (dimer)	-0.065	0.062	-10000	0	-0.25	11	11
negative regulation of transcription	-0.13	0.13	-10000	0	-0.28	112	112
FCGR2A	0.009	0.002	-10000	0	-10000	0	0
FER	0.004	0.002	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.005	0.07	-10000	0	-0.31	14	14
BLK	0.008	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insulin/Shc	0.013	0.002	-10000	0	-10000	0	0
RHOA	0.008	0.001	-10000	0	-10000	0	0
LEPR	0.009	0.026	-10000	0	-0.44	1	1
BCAR1	0.01	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.01	0	-10000	0	-10000	0	0
mol:NADPH	-0.005	0.002	-10000	0	-10000	0	0
TRPV6	-0.12	0.089	-10000	0	-0.22	12	12
PRL	0.001	0.004	-10000	0	-10000	0	0
SOCS3	0.015	0.075	-10000	0	-1.2	1	1
SPRY2	0.007	0.002	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.008	0.036	-10000	0	-0.26	5	5
CSF1/CSF1R	-0.063	0.061	-10000	0	-0.24	23	23
Ras protein signal transduction	0.026	0.017	-10000	0	-10000	0	0
IRS1	0.002	0.059	-10000	0	-0.44	5	5
INS	0	0.002	-10000	0	-10000	0	0
LEP	0.005	0.005	-10000	0	-10000	0	0
STAT5B	-0.091	0.073	-10000	0	-0.25	29	29
STAT5A	-0.091	0.073	-10000	0	-0.25	29	29
GRB2	0.01	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.074	0.069	-10000	0	-0.25	31	31
CSN2	-0.038	0.071	-10000	0	-10000	0	0
PIK3CA	0.01	0	-10000	0	-10000	0	0
LAT	-0.018	0.024	-10000	0	-10000	0	0
YBX1	0.011	0.001	-10000	0	-10000	0	0
LCK	0.01	0.001	-10000	0	-10000	0	0
SHC1	0.01	0	-10000	0	-10000	0	0
NOX4	-0.04	0.14	-10000	0	-0.45	30	30

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	-0.005	0.063	-10000	0	-0.22	24	24
epithelial cell differentiation	0.002	0.065	-10000	0	-0.22	24	24
CYFIP2	0.008	0.026	-10000	0	-0.44	1	1
ENAH	0.002	0.043	-10000	0	-10000	0	0
EGFR	0.01	0	-10000	0	-10000	0	0
EPHA2	0.01	0.001	-10000	0	-10000	0	0
MYO6	-0.006	0.06	-10000	0	-0.2	24	24
CTNNB1	0.01	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.019	0.016	-10000	0	-0.26	1	1
AQP5	-0.05	0.15	-10000	0	-0.44	33	33
CTNND1	0.01	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.006	0.059	-10000	0	-0.2	24	24
regulation of calcium-dependent cell-cell adhesion	-0.024	0.089	-10000	0	-0.23	44	44
EGF	-0.4	0.14	-10000	0	-0.44	261	261
NCKAP1	0.01	0	-10000	0	-10000	0	0
AQP3	-0.16	0.22	-10000	0	-0.44	107	107
cortical microtubule organization	0.002	0.065	-10000	0	-0.22	24	24
GO:0000145	-0.008	0.056	-10000	0	-0.19	24	24
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.003	0.066	-10000	0	-0.22	24	24
MLLT4	0.01	0	-10000	0	-10000	0	0
ARF6/GDP	-0.015	0.049	-10000	0	-0.18	24	24
ARF6	0.01	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.025	0.001	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.003	0.056	-10000	0	-0.19	24	24
PVRL2	0.01	0	-10000	0	-10000	0	0
ZYX	-0.006	0.06	-10000	0	-0.2	24	24
ARF6/GTP	0.028	0.002	-10000	0	-10000	0	0
CDH1	-0.027	0.12	-10000	0	-0.44	24	24
EGFR/EGFR/EGF/EGF	-0.19	0.08	-10000	0	-0.21	266	266
RhoA/GDP	0.003	0.062	-10000	0	-0.2	24	24
actin cytoskeleton organization	-0.006	0.059	-10000	0	-0.2	24	24
IGF-1R heterotetramer	0.01	0	-10000	0	-10000	0	0
GIT1	0.01	0	-10000	0	-10000	0	0
IGF1R	0.01	0	-10000	0	-10000	0	0
IGF1	0	0.064	-10000	0	-0.44	6	6
DIAPH1	0.019	0.035	-10000	0	-0.55	1	1
Wnt receptor signaling pathway	-0.002	0.065	0.22	24	-10000	0	24
RHOA	0.01	0	-10000	0	-10000	0	0
RhoA/GTP	-0.015	0.049	-10000	0	-0.18	24	24
CTNNA1	0.01	0	-10000	0	-10000	0	0
VCL	-0.006	0.06	-10000	0	-0.2	24	24
EFNA1	0.01	0	-10000	0	-10000	0	0
LPP	-0.006	0.057	-10000	0	-0.2	24	24
Ephrin A1/EPHA2	0.001	0.059	-10000	0	-0.2	24	24
SEC6/SEC8	-0.015	0.051	-10000	0	-0.18	24	24
MGAT3	-0.024	0.09	-10000	0	-0.23	44	44
HGF/MET	-0.012	0.077	-10000	0	-0.21	33	33
HGF	-0.017	0.11	-10000	0	-0.44	17	17
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.005	0.064	-10000	0	-0.22	24	24
actin cable formation	0.011	0.041	-10000	0	-10000	0	0
KIAA1543	-0.006	0.058	-10000	0	-0.2	25	25
KIFC3	-0.006	0.06	-10000	0	-0.2	24	24
NCK1	0.01	0	-10000	0	-10000	0	0
EXOC3	0.01	0	-10000	0	-10000	0	0
ACTN1	-0.006	0.06	-10000	0	-0.2	24	24
NCK1/GIT1	0.015	0	-10000	0	-10000	0	0
mol:GDP	0.002	0.065	-10000	0	-0.22	24	24
EXOC4	0.01	0	-10000	0	-10000	0	0
STX4	-0.006	0.06	-10000	0	-0.2	24	24
PIP5K1C	-0.006	0.06	-10000	0	-0.2	24	24
LIMA1	0.01	0	-10000	0	-10000	0	0
ABI1	0.01	0	-10000	0	-10000	0	0
ROCK1	0.001	0.049	-10000	0	-10000	0	0
adherens junction assembly	0	0.056	-10000	0	-0.22	1	1
IGF-1R heterotetramer/IGF1	-0.004	0.066	-10000	0	-0.2	30	30
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.015	0	-10000	0	-10000	0	0
MET	0.009	0.003	-10000	0	-10000	0	0
PLEKHA7	-0.006	0.061	-10000	0	-0.2	25	25
mol:GTP	0.024	0.001	-10000	0	-10000	0	0
establishment of epithelial cell apical/basal polarity	0	0.054	-10000	0	-0.18	24	24
cortical actin cytoskeleton stabilization	-0.005	0.063	-10000	0	-0.22	24	24
regulation of cell-cell adhesion	-0.006	0.059	-10000	0	-0.2	24	24
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.005	0.064	-10000	0	-0.22	24	24

×

Neurotrophic factor-mediated Trk receptor signaling

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
CRKL	0.01	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.026	0.072	-10000	0	-0.23	6	6
NT3 (dimer)/TRKC	-0.073	0.15	-10000	0	-0.33	73	73
NT3 (dimer)/TRKB	-0.12	0.16	-10000	0	-0.28	137	137
SHC/Grb2/SOS1/GAB1/PI3K	0.017	0	-10000	0	-10000	0	0
RAPGEF1	0.01	0	-10000	0	-10000	0	0
BDNF	0.008	0.003	-10000	0	-10000	0	0
PIK3CA	0.01	0	-10000	0	-10000	0	0
DYNLT1	0.01	0	-10000	0	-10000	0	0
NTRK1	-0.079	0.18	-10000	0	-0.44	56	56
NTRK2	-0.16	0.22	-10000	0	-0.44	113	113
NTRK3	-0.065	0.17	-10000	0	-0.44	48	48
NT-4/5 (dimer)/TRKB	-0.097	0.14	-10000	0	-0.26	119	119
neuron apoptosis	0.091	0.13	0.36	33	-10000	0	33
SHC 2-3/Grb2	-0.097	0.14	-10000	0	-0.39	33	33
SHC1	0.01	0	-10000	0	-10000	0	0
SHC2	-0.093	0.12	-10000	0	-0.38	29	29
SHC3	-0.1	0.15	-10000	0	-0.44	32	32
STAT3 (dimer)	0.013	0.02	-10000	0	-0.32	1	1
NT3 (dimer)/TRKA	-0.07	0.15	-10000	0	-0.3	82	82
RIN/GDP	-0.024	0.058	-10000	0	-0.18	7	7
GIPC1	0.01	0	-10000	0	-10000	0	0
KRAS	0.01	0	-10000	0	-10000	0	0
DNAJA3	-0.044	0.1	-10000	0	-0.22	67	67
RIN/GTP	0.001	0.002	-10000	0	-10000	0	0
CCND1	0.011	0.041	-10000	0	-0.68	1	1
MAGED1	0.01	0	-10000	0	-10000	0	0
PTPN11	0.01	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.005	0.005	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.02	0	-10000	0	-10000	0	0
GRB2	0.01	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.045	0.12	-10000	0	-0.26	66	66
TRKA/NEDD4-2	-0.05	0.13	-10000	0	-0.31	57	57
ELMO1	0.01	0	-10000	0	-10000	0	0
RhoG/GTP/ELMO1/DOCK1	0.013	0	-10000	0	-10000	0	0
NGF	-0.003	0.074	-10000	0	-0.44	8	8
HRAS	0.01	0	-10000	0	-10000	0	0
DOCK1	0.01	0	-10000	0	-10000	0	0
GAB2	0.01	0	-10000	0	-10000	0	0
RIT2	0.001	0.003	-10000	0	-10000	0	0
RIT1	0.01	0	-10000	0	-10000	0	0
FRS2	0.01	0	-10000	0	-10000	0	0
DNM1	0.005	0.027	-10000	0	-0.44	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.01	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.039	0.1	-10000	0	-0.21	67	67
mol:GDP	-0.034	0.082	-10000	0	-0.24	15	15
NGF (dimer)	-0.003	0.074	-10000	0	-0.44	8	8
RhoG/GDP	0.007	0	-10000	0	-10000	0	0
RIT1/GDP	-0.021	0.06	-10000	0	-0.18	7	7
TIAM1	0.01	0	-10000	0	-10000	0	0
PIK3R1	0.01	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.088	0.13	-10000	0	-0.25	113	113
KIDINS220/CRKL/C3G	0.015	0	-10000	0	-10000	0	0
SHC/RasGAP	0.015	0	-10000	0	-10000	0	0
FRS2 family/SHP2	0.02	0.002	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0.025	0	-10000	0	-10000	0	0
RIT1/GTP	0.007	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.039	0.14	-10000	0	-0.44	31	31
RAP1/GDP	-0.02	0.05	-10000	0	-0.16	7	7
KIDINS220/CRKL	0.01	0	-10000	0	-10000	0	0
BDNF (dimer)	0.008	0.003	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.043	0.12	-10000	0	-0.26	64	64
Schwann cell development	-0.028	0.025	-10000	0	-10000	0	0
EHD4	0.01	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.025	0.003	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.018	0.002	-10000	0	-10000	0	0
RAP1B	0.01	0	-10000	0	-10000	0	0
RAP1A	0.01	0	-10000	0	-10000	0	0
CDC42/GTP	-0.12	0.14	-10000	0	-0.24	142	142
ABL1	0.01	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.015	0	-10000	0	-10000	0	0
Rap1/GTP	-0.028	0.06	-10000	0	-10000	0	0
STAT3	0.013	0.02	-10000	0	-0.32	1	1
axon guidance	-0.11	0.13	-10000	0	-0.23	142	142
MAPK3	-0.04	0.11	-10000	0	-0.23	66	66
MAPK1	-0.04	0.11	-10000	0	-0.23	66	66
CDC42/GDP	-0.021	0.06	-10000	0	-0.18	7	7
NTF3	-0.039	0.14	-10000	0	-0.44	31	31
NTF4	0.005	0.005	-10000	0	-10000	0	0
NGF (dimer)/TRKA/FAIM	-0.042	0.12	-10000	0	-0.26	63	63
PI3K	0.015	0	-10000	0	-10000	0	0
FRS3	0.01	0.001	-10000	0	-10000	0	0
FAIM	0.01	0.001	-10000	0	-10000	0	0
GAB1	0.01	0	-10000	0	-10000	0	0
RASGRF1	-0.045	0.1	-10000	0	-0.22	66	66
SOS1	0.01	0	-10000	0	-10000	0	0
MCF2L	-0.062	0.13	-10000	0	-0.28	73	73
RGS19	0.01	0.001	-10000	0	-10000	0	0
CDC42	0.01	0	-10000	0	-10000	0	0
RAS family/GTP	0.004	0.043	-10000	0	-10000	0	0
Rac1/GDP	-0.021	0.06	-10000	0	-0.18	7	7
NGF (dimer)/TRKA/GRIT	-0.048	0.11	-10000	0	-0.26	63	63
neuron projection morphogenesis	-0.036	0.1	-10000	0	-0.46	4	4
NGF (dimer)/TRKA/NEDD4-2	-0.043	0.12	-10000	0	-0.26	64	64
MAP2K1	0.013	0	-10000	0	-10000	0	0
NGFR	-0.003	0.074	-10000	0	-0.44	8	8
NGF (dimer)/TRKA/GIPC/GAIP	-0.037	0.094	-10000	0	-0.22	49	49
RAS family/GTP/PI3K	0.014	0	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	0.029	0.003	-10000	0	-10000	0	0
NRAS	0.01	0	-10000	0	-10000	0	0
GRB2/SOS1	0.015	0	-10000	0	-10000	0	0
PRKCI	0.01	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCZ	0.01	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.12	0.22	-10000	0	-0.53	63	63
RASA1	0.01	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.049	0.13	-10000	0	-0.31	56	56
SQSTM1	0.009	0.002	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.075	0.12	-10000	0	-0.23	113	113
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.026	0.1	-10000	0	-0.22	61	61
MATK	0.004	0.046	-10000	0	-0.44	3	3
NEDD4L	0.008	0.026	-10000	0	-0.44	1	1
RAS family/GDP	-0.026	0.043	-10000	0	-0.15	7	7
NGF (dimer)/TRKA	-0.047	0.11	-10000	0	-0.23	67	67
Rac1/GTP	-0.049	0.072	-10000	0	-0.21	30	30
FRS2 family/SHP2/CRK family	0.029	0.003	-10000	0	-10000	0	0

×

Glucocorticoid receptor regulatory network

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
PCK2	-0.01	0.087	0.26	1	-0.78	3	4
SMARCC2	0.011	0	-10000	0	-10000	0	0
SMARCC1	0.011	0	-10000	0	-10000	0	0
TBX21	-0.002	0.068	-10000	0	-0.31	5	5
SUMO2	0.006	0.008	-10000	0	-10000	0	0
STAT1 (dimer)	0.013	0.002	-10000	0	-10000	0	0
FKBP4	0.01	0	-10000	0	-10000	0	0
FKBP5	0	0.064	-10000	0	-0.44	6	6
GR alpha/HSP90/FKBP51/HSP90	0.042	0.073	0.21	10	-0.22	5	15
PRL	-0.029	0.075	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/TIF2	0.067	0.18	0.42	25	-0.34	5	30
RELA	-0.07	0.1	-10000	0	-0.23	30	30
FGG	0.074	0.13	0.37	19	-10000	0	19
GR beta/TIF2	0.015	0.12	0.24	10	-0.28	26	36
IFNG	-0.065	0.16	-10000	0	-0.43	25	25
apoptosis	-0.06	0.21	0.36	2	-0.5	39	41
CREB1	0.002	0.052	-10000	0	-0.32	7	7
histone acetylation	-0.019	0.072	-10000	0	-0.28	7	7
BGLAP	-0.013	0.074	-10000	0	-0.39	1	1
GR/PKAc	0.048	0.061	0.21	9	-10000	0	9
NF kappa B1 p50/RelA	-0.12	0.18	-10000	0	-0.3	125	125
SMARCD1	0.011	0	-10000	0	-10000	0	0
MDM2	0.038	0.058	0.17	22	-10000	0	22
GATA3	-0.34	0.19	-10000	0	-0.44	225	225
AKT1	0.009	0.016	0.16	3	-10000	0	3
CSF2	-0.029	0.061	-10000	0	-0.4	1	1
GSK3B	0.006	0.008	-10000	0	-10000	0	0
NR1I3	-0.057	0.22	0.37	1	-0.67	20	21
CSN2	0.073	0.12	0.32	16	-10000	0	16
BRG1/BAF155/BAF170/BAF60A	0.029	0	-10000	0	-10000	0	0
NFATC1	0.011	0.002	-10000	0	-10000	0	0
POU2F1	0.01	0.004	-10000	0	-10000	0	0
CDKN1A	0.021	0.029	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.003	0.006	-10000	0	-10000	0	0
SFN	-0.002	0.058	-10000	0	-0.44	5	5
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.025	0.071	0.21	5	-0.26	6	11
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.075	0.26	0.36	1	-0.72	30	31
JUN	-0.045	0.16	0.26	3	-0.38	37	40
IL4	-0.017	0.074	-10000	0	-0.34	2	2
CDK5R1	0.007	0.005	-10000	0	-10000	0	0
PRKACA	0.01	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.019	0.098	0.22	13	-0.28	20	33
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.047	0.069	0.21	9	-0.2	4	13
cortisol/GR alpha (monomer)	0.098	0.18	0.49	24	-10000	0	24
NCOA2	-0.031	0.13	-10000	0	-0.44	26	26
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.05	0.17	-10000	0	-0.44	44	44
AP-1/NFAT1-c-4	-0.065	0.22	0.32	3	-0.52	35	38
AFP	-0.15	0.41	-10000	0	-1.3	32	32
SUV420H1	0.01	0	-10000	0	-10000	0	0
IRF1	0.061	0.094	0.35	5	-10000	0	5
TP53	0.021	0.013	-10000	0	-10000	0	0
PPP5C	0.01	0	-10000	0	-10000	0	0
KRT17	-0.1	0.3	-10000	0	-1	21	21
KRT14	-0.034	0.08	-10000	0	-0.36	1	1
TBP	0.014	0	-10000	0	-10000	0	0
CREBBP	0.006	0.017	-10000	0	-10000	0	0
HDAC1	0.009	0.001	-10000	0	-10000	0	0
HDAC2	0.009	0.002	-10000	0	-10000	0	0
AP-1	-0.065	0.22	0.32	3	-0.52	35	38
MAPK14	0.006	0.008	-10000	0	-10000	0	0
MAPK10	0.006	0.008	-10000	0	-10000	0	0
MAPK11	0.006	0.008	-10000	0	-10000	0	0
KRT5	-0.08	0.22	-10000	0	-0.65	21	21
interleukin-1 receptor activity	-0.001	0.002	-10000	0	-10000	0	0
NCOA1	0.01	0.009	-10000	0	-10000	0	0
STAT1	0.013	0.002	-10000	0	-10000	0	0
CGA	-0.039	0.17	-10000	0	-0.95	8	8
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.009	0.061	0.27	2	-10000	0	2
MAPK3	0.006	0.008	-10000	0	-10000	0	0
MAPK1	0.006	0.008	-10000	0	-10000	0	0
ICAM1	-0.12	0.18	-10000	0	-0.44	31	31
NFKB1	-0.07	0.1	-10000	0	-0.24	25	25
MAPK8	-0.036	0.13	-10000	0	-0.31	31	31
MAPK9	0.006	0.008	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.068	0.21	0.37	2	-0.53	39	41
BAX	0.019	0.022	-10000	0	-10000	0	0
POMC	-0.16	0.24	-10000	0	-0.7	20	20
EP300	0.006	0.017	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/p53	0.097	0.16	0.44	23	-10000	0	23
proteasomal ubiquitin-dependent protein catabolic process	0.026	0.047	0.16	7	-10000	0	7
SGK1	0.029	0.036	-10000	0	-10000	0	0
IL13	-0.31	0.24	-10000	0	-0.61	73	73
IL6	-0.19	0.34	-10000	0	-1	33	33
PRKACG	0.002	0.004	-10000	0	-10000	0	0
IL5	-0.27	0.2	-10000	0	-0.54	62	62
IL2	-0.067	0.16	-10000	0	-0.46	19	19
CDK5	0.007	0.005	-10000	0	-10000	0	0
PRKACB	0.01	0	-10000	0	-10000	0	0
HSP90AA1	0.01	0	-10000	0	-10000	0	0
IL8	-0.11	0.19	-10000	0	-0.46	28	28
CDK5R1/CDK5	0.01	0.009	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	-0.072	0.14	-10000	0	-0.32	25	25
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.093	0.15	0.4	26	-10000	0	26
SMARCA4	0.011	0	-10000	0	-10000	0	0
chromatin remodeling	0.069	0.095	0.3	12	-10000	0	12
NF kappa B1 p50/RelA/Cbp	-0.082	0.14	-10000	0	-0.32	31	31
JUN (dimer)	-0.045	0.16	0.26	3	-0.37	38	41
YWHAH	0.01	0	-10000	0	-10000	0	0
VIPR1	-0.032	0.17	-10000	0	-0.73	15	15
NR3C1	0.058	0.1	0.29	20	-10000	0	20
NR4A1	-0.18	0.23	-10000	0	-0.44	123	123
TIF2/SUV420H1	-0.015	0.093	-10000	0	-0.31	26	26
MAPKKK cascade	-0.06	0.21	0.36	2	-0.5	39	41
cortisol/GR alpha (dimer)/Src-1	0.092	0.16	0.42	26	-10000	0	26
PBX1	0.001	0.064	-10000	0	-0.44	6	6
POU1F1	0.005	0.006	-10000	0	-10000	0	0
SELE	-0.47	0.5	-10000	0	-0.95	149	149
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.069	0.096	0.3	12	-10000	0	12
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.093	0.15	0.4	26	-10000	0	26
mol:cortisol	0.048	0.1	0.26	26	-10000	0	26
MMP1	-0.083	0.27	-10000	0	-1.1	18	18

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	0.035	0.026	-10000	0	-0.26	1	1
FYN	0.051	0.065	0.28	13	-0.41	1	14
LAT/GRAP2/SLP76	0.036	0.03	-10000	0	-0.25	1	1
IKBKB	0.01	0	-10000	0	-10000	0	0
AKT1	0.067	0.076	0.25	29	-0.29	1	30
B2M	0.011	0.003	-10000	0	-10000	0	0
IKBKG	0.012	0.013	-10000	0	-0.086	1	1
MAP3K8	0.01	0	-10000	0	-10000	0	0
mol:Ca2+	-0.03	0.022	-10000	0	-0.047	172	172
integrin-mediated signaling pathway	0.013	0.002	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.075	0.087	0.31	23	-0.38	1	24
TRPV6	-0.31	0.2	0.23	2	-0.44	206	208
CD28	0.008	0.026	-10000	0	-0.44	1	1
SHC1	0.045	0.051	0.24	10	-0.3	1	11
receptor internalization	0.027	0.026	0.2	2	-0.22	1	3
PRF1	0.043	0.056	0.37	4	-10000	0	4
KRAS	0.01	0	-10000	0	-10000	0	0
GRB2	0.01	0	-10000	0	-10000	0	0
COT/AKT1	0.064	0.068	0.23	29	-0.23	1	30
LAT	0.049	0.052	0.25	8	-0.3	1	9
EntrezGene:6955	0.001	0.003	-10000	0	-10000	0	0
CD3D	0.009	0.004	-10000	0	-10000	0	0
CD3E	0.008	0.027	-10000	0	-0.44	1	1
CD3G	0.01	0.003	-10000	0	-10000	0	0
RASGRP2	0.015	0.019	0.066	10	-0.16	2	12
RASGRP1	0.072	0.086	0.27	29	-0.28	2	31
HLA-A	0.011	0.003	-10000	0	-10000	0	0
RASSF5	0.01	0.001	-10000	0	-10000	0	0
RAP1A/GTP/RAPL	0.013	0.002	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.051	0.048	0.13	47	-0.072	1	48
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.001	0.009	-10000	0	-0.14	1	1
PRKCA	0.04	0.035	0.13	17	-0.2	1	18
GRAP2	0.009	0.002	-10000	0	-10000	0	0
mol:IP3	0.14	0.098	0.2	198	-0.29	1	199
EntrezGene:6957	0.002	0.003	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	0.017	0.019	0.17	2	-10000	0	2
ORAI1	0.17	0.11	0.24	206	-0.16	2	208
CSK	0.041	0.044	0.22	6	-0.3	1	7
B7 family/CD28	0.027	0.029	0.27	1	-10000	0	1
CHUK	0.01	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	0.02	0.025	-10000	0	-0.33	1	1
PTPN6	0.033	0.036	0.24	3	-0.31	1	4
VAV1	0.043	0.054	0.28	3	-0.48	1	4
Monovalent TCR/CD3	0.011	0.015	-10000	0	-0.23	1	1
CBL	0.01	0	-10000	0	-10000	0	0
LCK	0.051	0.066	0.28	13	-0.4	1	14
PAG1	0.041	0.044	0.22	7	-0.3	1	8
RAP1A	0.01	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	0.021	0.025	-10000	0	-0.32	1	1
CD80	0.009	0.004	-10000	0	-10000	0	0
CD86	0.008	0.004	-10000	0	-10000	0	0
PDK1/CARD11/BCL10/MALT1	-0.001	0.01	-10000	0	-0.17	1	1
HRAS	0.01	0	-10000	0	-10000	0	0
GO:0035030	0.022	0.027	0.25	1	-10000	0	1
CD8A	0.01	0.003	-10000	0	-10000	0	0
CD8B	0.01	0.003	-10000	0	-10000	0	0
PTPRC	0.009	0.027	-10000	0	-0.44	1	1
PDK1/PKC theta	0.073	0.088	0.29	26	-0.34	1	27
CSK/PAG1	0.035	0.036	0.23	3	-0.29	1	4
SOS1	0.01	0	-10000	0	-10000	0	0
peptide-MHC class I	0.017	0.005	-10000	0	-10000	0	0
GRAP2/SLP76	0.035	0.028	-10000	0	-0.29	1	1
STIM1	0.08	0.053	-10000	0	-10000	0	0
RAS family/GTP	0.05	0.051	0.17	29	-10000	0	29
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	0.024	0.022	0.2	1	-0.22	1	2
mol:DAG	0.047	0.044	0.097	9	-0.27	1	10
RAP1A/GDP	0.023	0.022	0.072	32	-10000	0	32
PLCG1	0.01	0	-10000	0	-10000	0	0
CD247	0.01	0.003	-10000	0	-10000	0	0
cytotoxic T cell degranulation	0.043	0.056	0.37	4	-10000	0	4
RAP1A/GTP	0	0.005	-10000	0	-0.058	2	2
mol:PI-3-4-5-P3	0.072	0.083	0.27	29	-0.33	1	30
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.15	0.11	0.22	200	-0.37	1	201
NRAS	0.01	0	-10000	0	-10000	0	0
ZAP70	0.009	0.003	-10000	0	-10000	0	0
GRB2/SOS1	0.015	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	0.035	0.038	-10000	0	-0.39	1	1
MALT1	0.01	0	-10000	0	-10000	0	0
TRAF6	0.01	0	-10000	0	-10000	0	0
CD8 heterodimer	0.015	0.005	-10000	0	-10000	0	0
CARD11	0.007	0.004	-10000	0	-10000	0	0
PRKCB	0.04	0.035	0.13	18	-0.2	1	19
PRKCE	0.04	0.035	0.13	17	-0.2	1	18
PRKCQ	0.074	0.091	0.31	24	-0.38	1	25
LCP2	0.009	0.002	-10000	0	-10000	0	0
BCL10	0.01	0	-10000	0	-10000	0	0
regulation of survival gene product expression	0.064	0.073	0.24	29	-0.25	1	30
IKK complex	0.05	0.052	0.14	47	-10000	0	47
RAS family/GDP	0	0.002	-10000	0	-10000	0	0
MAP3K14	0.055	0.06	0.2	29	-0.18	1	30
PDPK1	0.067	0.076	0.25	29	-0.27	1	30
TCR/CD3/MHC I/CD8/Fyn	0.021	0.027	-10000	0	-0.4	1	1

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.002	0.029	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.029	0.075	-9999	-0.24	23	23
JUN	-0.016	0.077	-9999	-0.29	6	6
HRAS	0.01	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.012	0.086	-9999	-0.24	36	36
RAP1A	0.01	0	-9999	-10000	0	0
FRS2	0.01	0	-9999	-10000	0	0
RAP1A/GDP	0.007	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.012	0.085	-9999	-0.24	36	36
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.01	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.006	0.067	-9999	-0.23	23	23
RHOA	0.01	0	-9999	-10000	0	0
RAP1A/GTP	-0.009	0.077	-9999	-0.21	36	36
GRB7	0.01	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF	-0.012	0.086	-9999	-0.24	36	36
MAPKKK cascade	-0.012	0.079	-9999	-0.22	34	34
BCAR1	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.01	0.078	-9999	-0.25	26	26
lamellipodium assembly	-0.013	0.076	-9999	-0.23	23	23
RET51/GFRalpha1/GDNF/SHC	-0.012	0.086	-9999	-0.24	36	36
PIK3CA	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.006	0.067	-9999	-0.23	23	23
RET9/GFRalpha1/GDNF/Shank3	-0.006	0.067	-9999	-0.23	23	23
MAPK3	-0.013	0.073	-9999	-0.2	36	36
DOK1	0.01	0.001	-9999	-10000	0	0
DOK6	-0.057	0.16	-9999	-0.44	43	43
PXN	0.01	0	-9999	-10000	0	0
neurite development	-0.024	0.08	-9999	-0.29	8	8
DOK5	0.005	0.046	-9999	-0.44	3	3
GFRA1	-0.026	0.12	-9999	-0.44	23	23
MAPK8	-0.017	0.081	-9999	-0.22	38	38
HRAS/GTP	-0.013	0.088	-9999	-0.25	34	34
tube development	-0.004	0.063	-9999	-0.22	23	23
MAPK1	-0.013	0.073	-9999	-0.2	36	36
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.007	0.062	-9999	-0.22	23	23
Rac1/GDP	0.007	0	-9999	-10000	0	0
SRC	0.01	0.001	-9999	-10000	0	0
PDLIM7	0.01	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.041	0.12	-9999	-0.24	72	72
SHC1	0.01	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.012	0.086	-9999	-0.24	36	36
RET51/GFRalpha1/GDNF/Dok5	-0.015	0.089	-9999	-0.24	39	39
PRKCA	0.01	0	-9999	-10000	0	0
HRAS/GDP	0.007	0	-9999	-10000	0	0
CREB1	-0.012	0.078	-9999	-0.26	23	23
PIK3R1	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.007	0.062	-9999	-0.22	23	23
RET51/GFRalpha1/GDNF/Grb7	-0.012	0.086	-9999	-0.24	36	36
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.012	0.096	-9999	-0.44	14	14
DOK4	0.01	0	-9999	-10000	0	0
JNK cascade	-0.014	0.076	-9999	-0.28	6	6
RET9/GFRalpha1/GDNF/FRS2	-0.006	0.067	-9999	-0.23	23	23
SHANK3	0.01	0	-9999	-10000	0	0
RASA1	0.01	0	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.007	0.062	-9999	-0.22	23	23
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.015	0.079	-9999	-0.22	36	36
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.015	0.078	-9999	-0.22	34	34
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.015	0.081	-9999	-0.22	36	36
PI3K	-0.018	0.11	-9999	-0.34	23	23
SOS1	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	0	0.064	-9999	-0.22	23	23
GRB10	0.01	0	-9999	-10000	0	0
activation of MAPKK activity	-0.012	0.067	-9999	-0.21	23	23
RET51/GFRalpha1/GDNF/FRS2	-0.012	0.086	-9999	-0.24	36	36
GAB1	0.01	0	-9999	-10000	0	0
IRS1	0.002	0.059	-9999	-0.44	5	5
IRS2	0.01	0.001	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.015	0.081	-9999	-0.22	36	36
RET51/GFRalpha1/GDNF/PKC alpha	-0.012	0.086	-9999	-0.24	36	36
GRB2	0.01	0	-9999	-10000	0	0
PRKACA	0.01	0	-9999	-10000	0	0
GDNF	0.002	0.004	-9999	-10000	0	0
RAC1	0.01	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.017	0.095	-9999	-0.25	39	39
Rac1/GTP	-0.014	0.09	-9999	-0.27	23	23
RET9/GFRalpha1/GDNF	-0.013	0.073	-9999	-0.26	23	23
GFRalpha1/GDNF	-0.017	0.086	-9999	-0.31	23	23

×

Ephrin A reverse 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
MAPKKK cascade	-0.011	0.069	-9999	-0.26	21	21
EFNA5	-0.023	0.12	-9999	-0.44	21	21
FYN	-0.009	0.062	-9999	-0.23	21	21
neuron projection morphogenesis	-0.011	0.069	-9999	-0.26	21	21
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.011	0.069	-9999	-0.26	21	21
EPHA5	0.002	0.004	-9999	-10000	0	0

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	-0.8	0.56	-10000	0	-1.2	197	197
PLK1	0.083	0.078	-10000	0	-10000	0	0
CDKN1B	-0.048	0.1	-10000	0	-10000	0	0
FOXO3	0.068	0.057	-10000	0	-10000	0	0
KAT2B	0.022	0.01	-10000	0	-10000	0	0
FOXO1/SIRT1	-0.26	0.19	-10000	0	-0.39	197	197
CAT	0.072	0.058	-10000	0	-10000	0	0
CTNNB1	0.01	0	-10000	0	-10000	0	0
AKT1	-0.021	0.032	-10000	0	-10000	0	0
FOXO1	-0.28	0.2	-10000	0	-0.42	197	197
MAPK10	0.001	0.015	-10000	0	-10000	0	0
mol:GTP	0.001	0	-10000	0	-10000	0	0
FOXO4	0.02	0.033	-10000	0	-10000	0	0
response to oxidative stress	-0.026	0.03	-10000	0	-10000	0	0
FOXO3A/SIRT1	0.071	0.052	-10000	0	-10000	0	0
XPO1	0.01	0	-10000	0	-10000	0	0
EP300	-0.034	0.031	-10000	0	-10000	0	0
BCL2L11	0.022	0.015	-10000	0	-10000	0	0
FOXO1/SKP2	-0.25	0.19	-10000	0	-0.38	197	197
mol:GDP	-0.026	0.03	-10000	0	-10000	0	0
RAN	0.01	0	-10000	0	-10000	0	0
GADD45A	0.061	0.035	-10000	0	-10000	0	0
YWHAQ	0.01	0	-10000	0	-10000	0	0
FOXO1/14-3-3 family	-0.027	0.053	-10000	0	-10000	0	0
MST1	0.02	0.028	-10000	0	-0.42	1	1
CSNK1D	0.01	0	-10000	0	-10000	0	0
CSNK1E	0.01	0	-10000	0	-10000	0	0
FOXO4/14-3-3 family	0.032	0.039	-10000	0	-0.25	5	5
YWHAB	0.01	0	-10000	0	-10000	0	0
MAPK8	-0.003	0.034	-10000	0	-0.23	5	5
MAPK9	0.001	0.015	-10000	0	-10000	0	0
YWHAG	0.01	0	-10000	0	-10000	0	0
YWHAE	0.01	0	-10000	0	-10000	0	0
YWHAZ	0.01	0	-10000	0	-10000	0	0
SIRT1	0.009	0.008	-10000	0	-10000	0	0
SOD2	-0.055	0.12	0.31	1	-10000	0	1
RBL2	0.065	0.049	-10000	0	-10000	0	0
RAL/GDP	-0.003	0.021	-10000	0	-10000	0	0
CHUK	0.022	0.01	-10000	0	-10000	0	0
Ran/GTP	0.009	0.001	-10000	0	-10000	0	0
CSNK1G2	0.01	0	-10000	0	-10000	0	0
RAL/GTP	0.001	0.02	-10000	0	-10000	0	0
CSNK1G1	0.01	0	-10000	0	-10000	0	0
FASLG	0.039	0.056	-10000	0	-10000	0	0
SKP2	0.01	0	-10000	0	-10000	0	0
USP7	0.01	0	-10000	0	-10000	0	0
IKBKB	0.022	0.01	-10000	0	-10000	0	0
CCNB1	0.073	0.061	-10000	0	-10000	0	0
FOXO1-3a-4/beta catenin	-0.053	0.11	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.25	0.19	-10000	0	-0.38	197	197
CSNK1A1	0.01	0	-10000	0	-10000	0	0
SGK1	0.022	0.01	-10000	0	-10000	0	0
CSNK1G3	0.01	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.016	0.002	-10000	0	-10000	0	0
ZFAND5	0.022	0.029	-10000	0	-10000	0	0
SFN	-0.002	0.058	-10000	0	-0.44	5	5
CDK2	-0.054	0.045	-10000	0	-10000	0	0
FOXO3A/14-3-3	0.047	0.037	-10000	0	-10000	0	0
CREBBP	-0.054	0.045	-10000	0	-10000	0	0
FBXO32	0.073	0.061	-10000	0	-10000	0	0
BCL6	0.066	0.05	-10000	0	-10000	0	0
RALB	0.01	0	-10000	0	-10000	0	0
RALA	0.01	0	-10000	0	-10000	0	0
YWHAH	0.01	0	-10000	0	-10000	0	0

×

Nongenotropic Androgen 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
PTK2	0.004	0	-10000	0	-10000	0	0
GNB1/GNG2	0.008	0.05	-10000	0	-0.23	12	12
regulation of S phase of mitotic cell cycle	0.003	0.045	-10000	0	-0.21	12	12
GNAO1	-0.029	0.13	-10000	0	-0.44	25	25
HRAS	0.009	0.001	-10000	0	-10000	0	0
SHBG/T-DHT	-0.002	0.047	-10000	0	-0.26	9	9
PELP1	0.009	0.001	-10000	0	-10000	0	0
AKT1	0.005	0	-10000	0	-10000	0	0
MAP2K1	-0.013	0.059	-10000	0	-0.21	11	11
T-DHT/AR	-0.008	0.064	-10000	0	-0.31	12	12
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	-10000	0	-0.007	44	44
GNAI2	0.01	0	-10000	0	-10000	0	0
GNAI3	0.01	0	-10000	0	-10000	0	0
GNAI1	0.007	0.037	-10000	0	-0.44	2	2
mol:GDP	-0.01	0.074	-10000	0	-0.37	12	12
cell proliferation	-0.048	0.14	-10000	0	-0.38	44	44
PIK3CA	0.01	0	-10000	0	-10000	0	0
FOS	-0.1	0.28	-10000	0	-0.76	44	44
mol:Ca2+	-0.005	0.019	-10000	0	-0.055	29	29
MAPK3	-0.032	0.1	-10000	0	-0.26	43	43
MAPK1	-0.021	0.075	-10000	0	-0.19	44	44
PIK3R1	0.01	0	-10000	0	-10000	0	0
mol:IP3	-0.001	0.002	-10000	0	-0.004	44	44
cAMP biosynthetic process	-0.004	0.045	-10000	0	-0.24	9	9
GNG2	0.01	0	-10000	0	-10000	0	0
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.004	44	44
HRAS/GTP	0.001	0.05	-10000	0	-0.21	12	12
actin cytoskeleton reorganization	0.015	0.001	-10000	0	-10000	0	0
SRC	0.009	0.001	-10000	0	-10000	0	0
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.004	44	44
PI3K	0.013	0	-10000	0	-10000	0	0
apoptosis	0.048	0.15	0.4	44	-10000	0	44
T-DHT/AR/PELP1	-0.001	0.055	-10000	0	-0.26	12	12
HRAS/GDP	-0.005	0.072	-10000	0	-0.35	12	12
CREB1	-0.052	0.16	-10000	0	-0.42	44	44
RAC1-CDC42/GTP	0.019	0.001	-10000	0	-10000	0	0
AR	-0.009	0.09	-10000	0	-0.44	12	12
GNB1	0.01	0	-10000	0	-10000	0	0
RAF1	-0.008	0.053	-10000	0	-0.21	11	11
RAC1-CDC42/GDP	0.003	0.07	-10000	0	-0.33	12	12
T-DHT/AR/PELP1/Src	0.004	0.051	-10000	0	-0.23	12	12
MAP2K2	-0.013	0.059	-10000	0	-0.21	11	11
T-DHT/AR/PELP1/Src/PI3K	0.003	0.045	-10000	0	-0.21	12	12
GNAZ	0.01	0	-10000	0	-10000	0	0
SHBG	-0.004	0.078	-10000	0	-0.44	9	9
Gi family/GNB1/GNG2/GDP	-0.012	0.088	-10000	0	-0.29	25	25
mol:T-DHT	0	0.001	-10000	0	-0.002	42	42
RAC1	0.01	0	-10000	0	-10000	0	0
GNRH1	0.003	0.002	-10000	0	-10000	0	0
Gi family/GTP	-0.012	0.057	-10000	0	-0.17	27	27
CDC42	0.01	0	-10000	0	-10000	0	0

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.009	0.057	-10000	0	-0.22	17	17
ER alpha/Gai/GDP/Gbeta gamma	-0.025	0.13	-10000	0	-0.34	37	37
AKT1	-0.029	0.18	-10000	0	-0.74	17	17
PIK3CA	0.01	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.029	0.18	-10000	0	-0.75	17	17
mol:Ca2+	-0.09	0.17	-10000	0	-0.38	63	63
IGF1R	0.01	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	-0.007	0.072	-10000	0	-0.26	22	22
SHC1	0.01	0	-10000	0	-10000	0	0
apoptosis	0.027	0.17	0.7	17	-10000	0	17
RhoA/GTP	-0.002	0.047	-10000	0	-0.19	17	17
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.016	0.12	-10000	0	-0.42	17	17
regulation of stress fiber formation	0	0.046	0.16	22	-10000	0	22
E2/ERA-ERB (dimer)	-0.003	0.064	-10000	0	-0.26	17	17
KRAS	0.01	0	-10000	0	-10000	0	0
G13/GTP	-0.002	0.058	-10000	0	-0.23	17	17
pseudopodium formation	0	0.046	-10000	0	-0.16	22	22
E2/ER alpha (dimer)/PELP1	-0.003	0.064	-10000	0	-0.26	17	17
GRB2	0.01	0	-10000	0	-10000	0	0
GNG2	0.01	0	-10000	0	-10000	0	0
GNAO1	-0.029	0.13	-10000	0	-0.44	25	25
HRAS	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.024	0.14	-10000	0	-0.51	19	19
E2/ER beta (dimer)	0.007	0	-10000	0	-10000	0	0
mol:GDP	-0.007	0.082	-10000	0	-0.34	17	17
mol:NADP	-0.024	0.14	-10000	0	-0.51	19	19
PIK3R1	0.01	0	-10000	0	-10000	0	0
mol:IP3	-0.093	0.18	-10000	0	-0.39	63	63
IGF-1R heterotetramer	0.01	0	-10000	0	-10000	0	0
PLCB1	-0.1	0.18	-10000	0	-0.41	63	63
PLCB2	-0.073	0.16	-10000	0	-0.37	61	61
IGF1	0	0.064	-10000	0	-0.44	6	6
mol:L-citrulline	-0.024	0.14	-10000	0	-0.51	19	19
RHOA	0.01	0	-10000	0	-10000	0	0
Gai/GDP	-0.04	0.19	-10000	0	-0.64	25	25
JNK cascade	0.007	0	-10000	0	-10000	0	0
BCAR1	0.01	0	-10000	0	-10000	0	0
ESR2	0.01	0.001	-10000	0	-10000	0	0
GNAQ	0.01	0	-10000	0	-10000	0	0
ESR1	-0.017	0.11	-10000	0	-0.44	17	17
Gq family/GDP/Gbeta gamma	-0.033	0.1	-10000	0	-0.38	7	7
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.002	0.062	-10000	0	-0.27	5	5
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.016	0.12	-10000	0	-0.42	17	17
GNAZ	0.01	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)	-0.011	0.075	-10000	0	-0.31	17	17
STRN	0.002	0.059	-10000	0	-0.44	5	5
GNAL	0.008	0.026	-10000	0	-0.44	1	1
PELP1	0.01	0	-10000	0	-10000	0	0
MAPK11	0.008	0	-10000	0	-10000	0	0
GNAI2	0.01	0	-10000	0	-10000	0	0
GNAI3	0.01	0	-10000	0	-10000	0	0
GNAI1	0.007	0.037	-10000	0	-0.44	2	2
HBEGF	-0.004	0.12	-10000	0	-0.31	33	33
cAMP biosynthetic process	-0.002	0.052	-10000	0	-0.21	18	18
SRC	-0.023	0.13	-10000	0	-0.32	37	37
PI3K	0.015	0	-10000	0	-10000	0	0
GNB1	0.01	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	0.004	0.075	-10000	0	-0.3	17	17
SOS1	0.01	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.035	0.097	-10000	0	-0.35	19	19
Gs family/GTP	0	0.054	-10000	0	-0.21	18	18
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.019	0	-10000	0	-10000	0	0
vasodilation	-0.023	0.14	-10000	0	-0.49	19	19
mol:DAG	-0.093	0.18	-10000	0	-0.39	63	63
Gs family/GDP/Gbeta gamma	-0.004	0.071	-10000	0	-0.29	17	17
MSN	-0.001	0.048	-10000	0	-0.17	22	22
Gq family/GTP	-0.077	0.17	-10000	0	-0.4	61	61
mol:PI-3-4-5-P3	-0.027	0.18	-10000	0	-0.72	17	17
NRAS	0.01	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.023	0.14	0.49	19	-10000	0	19
GRB2/SOS1	0.015	0	-10000	0	-10000	0	0
RhoA/GDP	-0.001	0.08	-10000	0	-0.32	17	17
NOS3	-0.026	0.15	-10000	0	-0.54	19	19
GNA11	-0.001	0.069	-10000	0	-0.44	7	7
MAPKKK cascade	-0.021	0.15	-10000	0	-0.51	22	22
E2/ER alpha (dimer)/PELP1/Src	-0.018	0.12	-10000	0	-0.44	17	17
ruffle organization	0	0.046	-10000	0	-0.16	22	22
ROCK2	-0.001	0.052	-10000	0	-0.18	22	22
GNA14	-0.085	0.18	-10000	0	-0.44	61	61
GNA15	0.009	0.002	-10000	0	-10000	0	0
GNA13	0.01	0.001	-10000	0	-10000	0	0
MMP9	0.002	0.13	-10000	0	-0.3	33	33
MMP2	-0.019	0.12	-10000	0	-0.31	37	37

×

LPA4-mediated signaling events

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
ADCY4	-0.01	0.063	-9999	-0.26	17	17
ADCY5	-0.01	0.063	-9999	-0.26	17	17
ADCY6	0.005	0	-9999	-10000	0	0
ADCY7	0.005	0.001	-9999	-10000	0	0
ADCY1	-0.12	0.13	-9999	-0.26	140	140
ADCY2	0.001	0.016	-9999	-0.26	1	1
ADCY3	0.005	0	-9999	-10000	0	0
ADCY8	0.004	0.002	-9999	-10000	0	0
PRKCE	0.005	0	-9999	-10000	0	0
ADCY9	0.005	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.006	0.049	-9999	-0.16	4	4

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.016	0.031	0.15	5	-10000	0	5
NFATC2	-0.005	0.079	0.15	5	-0.26	22	27
NFATC3	0.016	0.031	0.15	5	-10000	0	5
CD40LG	-0.016	0.17	0.35	15	-0.39	26	41
PTGS2	-0.043	0.24	0.35	19	-0.5	48	67
JUNB	0.01	0	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0.006	0.012	-10000	0	-10000	0	0
CaM/Ca2+	0.006	0.012	-10000	0	-10000	0	0
CALM1	0.01	0.011	-10000	0	-10000	0	0
JUN	0.01	0.011	-10000	0	-10000	0	0
mol:Ca2+	-0.002	0.005	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.007	0.006	-10000	0	-10000	0	0
FOSL1	0.007	0.037	-10000	0	-0.44	2	2
CREM	0.01	0	-10000	0	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.008	0.075	-10000	0	-0.23	14	14
FOS	-0.058	0.16	-10000	0	-0.44	44	44
IFNG	-0.029	0.16	0.32	7	-0.39	26	33
AP-1/NFAT1-c-4	-0.048	0.16	-10000	0	-0.44	26	26
FASLG	-0.033	0.15	0.37	3	-0.39	26	29
NFAT1-c-4/ICER1	0.001	0.073	-10000	0	-0.22	19	19
IL2RA	-0.033	0.15	0.32	9	-0.39	26	35
FKBP12/FK506	0.007	0	-10000	0	-10000	0	0
CSF2	-0.023	0.17	0.36	11	-0.39	26	37
JunB/Fra1/NFAT1-c-4	0.003	0.075	-10000	0	-0.21	21	21
IL4	-0.031	0.16	0.35	5	-0.39	26	31
IL2	-0.004	0.01	-10000	0	-10000	0	0
IL3	-0.007	0.016	-10000	0	-10000	0	0
FKBP1A	0.01	0	-10000	0	-10000	0	0
BATF3	0.01	0.001	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.01	0	-10000	0	-10000	0	0

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.006	0.082	-9999	-0.44	10	10
mol:S1P	0.001	0	-9999	-10000	0	0
S1P1/S1P/Gi	-0.004	0.06	-9999	-0.19	27	27
GNAO1	-0.028	0.13	-9999	-0.44	25	25
S1P/S1P3/G12/G13	0	0.068	-9999	-0.23	23	23
AKT1	-0.016	0.11	-9999	-0.57	10	10
AKT3	-0.003	0.064	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.006	0.082	-9999	-0.44	10	10
GNAI2	0.01	0	-9999	-10000	0	0
GNAI3	0.01	0	-9999	-10000	0	0
GNAI1	0.007	0.037	-9999	-0.44	2	2
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	-0.025	0.12	-9999	-0.44	23	23
S1PR2	0.01	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	-0.021	0.11	-9999	-0.25	42	42
MAPK3	-0.02	0.1	-9999	-0.24	42	42
MAPK1	-0.02	0.1	-9999	-0.46	7	7
JAK2	-0.016	0.11	-9999	-0.25	41	41
CXCR4	-0.021	0.1	-9999	-0.24	41	41
FLT1	0.008	0.037	-9999	-0.44	2	2
RhoA/GDP	0.007	0	-9999	-10000	0	0
Rac1/GDP	0.007	0	-9999	-10000	0	0
SRC	-0.02	0.1	-9999	-0.24	42	42
S1P/S1P3/Gi	-0.022	0.11	-9999	-0.26	42	42
RAC1	0.01	0	-9999	-10000	0	0
RhoA/GTP	-0.015	0.099	-9999	-0.49	6	6
VEGFA	0.011	0.001	-9999	-10000	0	0
S1P/S1P2/Gi	-0.003	0.066	-9999	-0.21	27	27
VEGFR1 homodimer/VEGFA homodimer	0.015	0.027	-9999	-0.31	2	2
RHOA	0.01	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.057	0.13	-9999	-0.26	74	74
GNAQ	0.01	0	-9999	-10000	0	0
GNAZ	0.01	0	-9999	-10000	0	0
G12/G13	0.015	0.001	-9999	-10000	0	0
GNA14	-0.085	0.18	-9999	-0.44	61	61
GNA15	0.009	0.002	-9999	-10000	0	0
GNA12	0.01	0	-9999	-10000	0	0
GNA13	0.01	0.001	-9999	-10000	0	0
GNA11	-0.001	0.069	-9999	-0.44	7	7
Rac1/GTP	-0.015	0.099	-9999	-0.23	42	42

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.007	0.037	-9999	-10000	0	0
adherens junction organization	-0.008	0.069	-9999	-0.23	24	24
mol:GTP	0	0	-9999	-10000	0	0
Rac1/GDP	0.011	0.037	-9999	-10000	0	0
FMN1	-0.017	0.083	-9999	-0.22	40	40
mol:IP3	0.005	0.038	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.005	0.068	-9999	-0.23	24	24
CTNNB1	0.01	0.002	-9999	-10000	0	0
AKT1	0.006	0.045	-9999	-10000	0	0
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.031	0.1	-9999	-0.38	24	24
CTNND1	0.01	0.001	-9999	-10000	0	0
mol:PI-4-5-P2	-0.003	0.064	-9999	-0.22	24	24
VASP	-0.003	0.065	-9999	-0.22	24	24
ZYX	-0.003	0.065	-9999	-0.22	24	24
JUB	-0.003	0.065	-9999	-0.22	24	24
EGFR(dimer)	0.001	0.066	-9999	-0.22	24	24
E-cadherin/beta catenin-gamma catenin	-0.002	0.072	-9999	-0.24	24	24
mol:PI-3-4-5-P3	0.008	0.048	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
PI3K	0.008	0.049	-9999	-10000	0	0
FYN	-0.13	0.088	-9999	-0.28	15	15
mol:Ca2+	0.005	0.037	-9999	-10000	0	0
JUP	0.01	0.002	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
mol:DAG	0.005	0.038	-9999	-10000	0	0
CDH1	-0.028	0.12	-9999	-0.44	24	24
RhoA/GDP	0.011	0.037	-9999	-10000	0	0
establishment of polarity of embryonic epithelium	-0.003	0.064	-9999	-0.22	24	24
SRC	0.01	0.001	-9999	-10000	0	0
RAC1	0.01	0	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
EGFR	0.01	0	-9999	-10000	0	0
CASR	-0.15	0.095	-9999	-0.2	213	213
RhoA/GTP	0.009	0.036	-9999	-10000	0	0
AKT2	0.006	0.045	-9999	-10000	0	0
actin cable formation	-0.015	0.081	-9999	-0.21	40	40
apoptosis	-0.005	0.043	-9999	-10000	0	0
CTNNA1	0.01	0.001	-9999	-10000	0	0
mol:GDP	0.006	0.038	-9999	-10000	0	0
PIP5K1A	-0.003	0.065	-9999	-0.22	24	24
PLCG1	0.005	0.038	-9999	-10000	0	0
Rac1/GTP	0.005	0.063	-9999	-0.2	24	24
homophilic cell adhesion	0	0.001	-9999	-10000	0	0

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.003	0.077	-9999	-0.26	24	24
E-cadherin/beta catenin	-0.012	0.089	-9999	-0.31	24	24
CTNNB1	0.01	0	-9999	-10000	0	0
JUP	0.01	0	-9999	-10000	0	0
CDH1	-0.027	0.12	-9999	-0.44	24	24

×

Signaling events mediated by the Hedgehog family

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
TGFB2	0.005	0.075	-10000	0	-10000	0	0
IHH	-0.03	0.14	-10000	0	-0.47	28	28
SHH Np/Cholesterol/GAS1	-0.004	0.062	-10000	0	-0.23	20	20
LRPAP1	0.01	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.004	0.061	0.23	20	-10000	0	20
SMO/beta Arrestin2	-0.003	0.1	-10000	0	-0.32	23	23
SMO	-0.01	0.11	-10000	0	-0.33	25	25
AKT1	0.008	0.053	-10000	0	-0.26	1	1
ARRB2	0.01	0.001	-10000	0	-10000	0	0
BOC	0.01	0	-10000	0	-10000	0	0
ADRBK1	0.01	0	-10000	0	-10000	0	0
heart looping	-0.009	0.1	-10000	0	-0.33	25	25
STIL	0.001	0.063	-10000	0	-10000	0	0
DHH N/PTCH2	-0.007	0.08	-10000	0	-0.31	19	19
DHH N/PTCH1	-0.014	0.097	-10000	0	-0.24	43	43
PIK3CA	0.01	0	-10000	0	-10000	0	0
DHH	-0.02	0.11	-10000	0	-0.44	19	19
PTHLH	-0.006	0.097	-10000	0	-10000	0	0
determination of left/right symmetry	-0.009	0.1	-10000	0	-0.33	25	25
PIK3R1	0.01	0	-10000	0	-10000	0	0
skeletal system development	-0.006	0.096	-10000	0	-10000	0	0
IHH N/Hhip	-0.023	0.1	-10000	0	-0.29	39	39
DHH N/Hhip	-0.02	0.1	-10000	0	-0.34	27	27
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.009	0.1	-10000	0	-0.33	25	25
pancreas development	-0.008	0.086	-10000	0	-0.44	11	11
HHAT	0.01	0	-10000	0	-10000	0	0
PI3K	0.015	0	-10000	0	-10000	0	0
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.017	0.11	-10000	0	-0.44	17	17
somite specification	-0.009	0.1	-10000	0	-0.33	25	25
SHH Np/Cholesterol/PTCH1	0.002	0.068	-10000	0	-10000	0	0
SHH Np/Cholesterol/PTCH2	0.01	0.025	-10000	0	-0.23	3	3
SHH Np/Cholesterol/Megalin	-0.012	0.077	-10000	0	-0.24	29	29
SHH	0.006	0.032	-10000	0	-0.31	3	3
catabolic process	-0.003	0.085	-10000	0	-0.27	25	25
SMO/Vitamin D3	-0.001	0.087	-10000	0	-0.26	23	23
SHH Np/Cholesterol/Hhip	0	0.053	-10000	0	-0.23	14	14
LRP2	-0.032	0.13	-10000	0	-0.44	27	27
receptor-mediated endocytosis	-0.018	0.11	-10000	0	-0.44	10	10
SHH Np/Cholesterol/BOC	0.01	0.025	-10000	0	-0.23	3	3
SHH Np/Cholesterol/CDO	0.01	0.025	-10000	0	-0.23	3	3
mesenchymal cell differentiation	0	0.052	0.23	14	-10000	0	14
mol:Vitamin D3	0.004	0.07	-10000	0	-10000	0	0
IHH N/PTCH2	-0.01	0.085	-10000	0	-0.27	28	28
CDON	0.01	0.001	-10000	0	-10000	0	0
IHH N/PTCH1	0.001	0.087	-10000	0	-0.27	25	25
Megalin/LRPAP1	-0.016	0.094	-10000	0	-0.31	27	27
PTCH2	0.01	0.001	-10000	0	-10000	0	0
SHH Np/Cholesterol	0.005	0.025	-10000	0	-0.24	3	3
PTCH1	-0.003	0.085	-10000	0	-0.27	25	25
HHIP	-0.008	0.086	-10000	0	-0.44	11	11

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.01	0.002	-10000	0	-10000	0	0
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	-0.076	0.089	-10000	0	-10000	0	0
IL27/IL27R/JAK1	0.2	0.17	0.42	7	-10000	0	7
TBX21	0.21	0.15	0.36	100	-10000	0	100
IL12B	0.006	0.006	-10000	0	-10000	0	0
IL12A	0.005	0.002	-10000	0	-10000	0	0
IL6ST	-0.043	0.16	-10000	0	-0.43	44	44
IL27RA/JAK1	0.065	0.037	-10000	0	-10000	0	0
IL27	0.02	0.011	-10000	0	-10000	0	0
TYK2	0.018	0.006	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.024	0.082	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.076	0.089	-10000	0	-10000	0	0
T cell proliferation during immune response	-0.076	0.089	-10000	0	-10000	0	0
MAPKKK cascade	0.076	0.089	-10000	0	-10000	0	0
STAT3	0.01	0	-10000	0	-10000	0	0
STAT2	0.01	0	-10000	0	-10000	0	0
STAT1	0.02	0.007	-10000	0	-10000	0	0
IL12RB1	0.009	0.003	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	0.07	0.12	0.35	5	-0.38	1	6
IL27/IL27R/JAK2/TYK2	0.076	0.089	-10000	0	-10000	0	0
positive regulation of T cell mediated cytotoxicity	0.076	0.089	-10000	0	-10000	0	0
STAT1 (dimer)	0.34	0.26	0.52	188	-10000	0	188
JAK2	0.014	0.004	-10000	0	-10000	0	0
JAK1	0.02	0.007	-10000	0	-10000	0	0
STAT2 (dimer)	0.066	0.092	-10000	0	-10000	0	0
T cell proliferation	0.054	0.11	-10000	0	-0.35	4	4
IL12/IL12R/TYK2/JAK2	0.027	0.038	-10000	0	-10000	0	0
IL17A	-0.023	0.081	-10000	0	-10000	0	0
mast cell activation	-0.076	0.089	-10000	0	-10000	0	0
IFNG	0.023	0.026	0.084	17	-10000	0	17
T cell differentiation	0	0.002	-10000	0	-10000	0	0
STAT3 (dimer)	0.066	0.092	-10000	0	-10000	0	0
STAT5A (dimer)	0.066	0.092	-10000	0	-10000	0	0
STAT4 (dimer)	0.06	0.09	-10000	0	-10000	0	0
STAT4	0.009	0.003	-10000	0	-10000	0	0
T cell activation	-0.006	0.004	-10000	0	-10000	0	0
IL27R/JAK2/TYK2	0.007	0.079	-10000	0	-10000	0	0
GATA3	-0.92	0.5	-10000	0	-1.2	225	225
IL18	0.005	0.001	-10000	0	-10000	0	0
positive regulation of mast cell cytokine production	0.066	0.091	-10000	0	-10000	0	0
IL27/EBI3	0.035	0.03	-10000	0	-0.3	1	1
IL27RA	0.023	0.029	-10000	0	-10000	0	0
IL6	-0.036	0.14	-10000	0	-0.44	29	29
STAT5A	0.01	0	-10000	0	-10000	0	0
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	-0.001	0.007	-10000	0	-10000	0	0
IL1B	-0.001	0.041	-10000	0	-0.31	5	5
EBI3	0.02	0.029	-10000	0	-0.43	1	1
TNF	0.001	0.032	-10000	0	-0.31	3	3

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.02	0.15	-10000	0	-0.51	1	1
CRP	0.022	0.16	0.44	2	-0.51	1	3
cell cycle arrest	0.012	0.16	0.4	8	-0.55	2	10
TIMP1	0.035	0.16	0.46	6	-0.49	1	7
IL6ST	-0.054	0.16	-10000	0	-0.44	44	44
Rac1/GDP	0.003	0.12	0.24	9	-0.3	18	27
AP1	-0.017	0.12	-10000	0	-0.29	12	12
GAB2	0.01	0.002	-10000	0	-10000	0	0
TNFSF11	0.022	0.16	0.44	4	-0.51	1	5
HSP90B1	0.018	0.046	-10000	0	-10000	0	0
GAB1	0.01	0.001	-10000	0	-10000	0	0
MAPK14	-0.028	0.11	-10000	0	-0.46	7	7
AKT1	0.023	0.014	-10000	0	-10000	0	0
FOXO1	0.024	0.013	-10000	0	-10000	0	0
MAP2K6	-0.024	0.12	-10000	0	-0.32	18	18
mol:GTP	0.001	0.002	-10000	0	-10000	0	0
MAP2K4	0.019	0.13	0.3	11	-0.38	7	18
MITF	-0.02	0.12	0.2	4	-0.3	22	26
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.01	0	-10000	0	-10000	0	0
A2M	0	0.1	-10000	0	-1.2	2	2
CEBPB	0.006	0.011	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.002	0.058	-10000	0	-10000	0	0
STAT3	0.003	0.16	0.4	8	-0.58	2	10
STAT1	0.011	0.015	-10000	0	-10000	0	0
CEBPD	0.02	0.15	-10000	0	-0.51	1	1
PIK3CA	0.01	0	-10000	0	-10000	0	0
PI3K	0.016	0.001	-10000	0	-10000	0	0
JUN	0.009	0.001	-10000	0	-10000	0	0
PIAS3/MITF	-0.016	0.12	-10000	0	-0.3	18	18
MAPK11	-0.028	0.11	-10000	0	-0.46	7	7
STAT3 (dimer)/FOXO1	0.02	0.15	0.38	8	-0.46	3	11
GRB2/SOS1/GAB family	-0.023	0.1	-10000	0	-0.42	7	7
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.035	0.12	-10000	0	-0.26	40	40
GRB2	0.01	0.001	-10000	0	-10000	0	0
JAK2	0.01	0	-10000	0	-10000	0	0
LBP	-0.19	0.43	0.45	2	-0.85	82	84
PIK3R1	0.01	0	-10000	0	-10000	0	0
JAK1	0.012	0.004	-10000	0	-10000	0	0
MYC	0.021	0.15	-10000	0	-0.51	1	1
FGG	0.023	0.16	0.44	8	-0.51	1	9
macrophage differentiation	0.012	0.16	0.4	8	-0.55	2	10
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.025	0.11	-10000	0	-0.23	60	60
JUNB	0.02	0.15	-10000	0	-0.5	1	1
FOS	-0.059	0.16	-10000	0	-0.44	44	44
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.022	0.13	0.2	4	-0.32	22	26
STAT1/PIAS1	-0.008	0.12	0.23	8	-0.32	16	24
GRB2/SOS1/GAB family/SHP2/PI3K	0.021	0.015	-10000	0	-10000	0	0
STAT3 (dimer)	0.007	0.16	0.4	8	-0.56	2	10
PRKCD	0.03	0.14	0.35	11	-0.41	4	15
IL6R	0.01	0.027	-10000	0	-0.44	1	1
SOCS3	-0.03	0.12	-10000	0	-0.56	6	6
gp130 (dimer)/JAK1/JAK1/LMO4	-0.013	0.1	-10000	0	-0.25	44	44
Rac1/GTP	-0.012	0.11	0.23	4	-0.3	18	22
HCK	0.007	0.026	-10000	0	-0.44	1	1
MAPKKK cascade	0.012	0.051	-10000	0	-10000	0	0
bone resorption	0.024	0.15	0.43	4	-0.49	1	5
IRF1	0.02	0.15	-10000	0	-0.51	1	1
mol:GDP	-0.012	0.12	0.23	8	-0.31	20	28
SOS1	0.01	0.002	-10000	0	-10000	0	0
VAV1	-0.015	0.12	0.23	8	-0.31	20	28
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.034	0.11	-10000	0	-0.5	7	7
PTPN11	0.011	0.016	-10000	0	-10000	0	0
IL6/IL6RA	-0.015	0.099	-10000	0	-0.3	30	30
gp130 (dimer)/TYK2/TYK2/LMO4	-0.015	0.1	-10000	0	-0.25	44	44
gp130 (dimer)/JAK2/JAK2/LMO4	-0.015	0.1	-10000	0	-0.25	44	44
IL6	-0.032	0.14	-10000	0	-0.44	29	29
PIAS3	0.01	0	-10000	0	-10000	0	0
PTPRE	0.002	0.013	-10000	0	-10000	0	0
PIAS1	0.01	0	-10000	0	-10000	0	0
RAC1	0.01	0.001	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.038	0.12	-10000	0	-0.26	49	49
LMO4	0.014	0.009	-10000	0	-10000	0	0
STAT3 (dimer)/PIAS3	0	0.15	0.36	4	-0.52	4	8
MCL1	0.025	0.013	-10000	0	-10000	0	0

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.01	0.001	-9999	-10000	0	0
CCL5	0.009	0.003	-9999	-10000	0	0
SDCBP	0.01	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	0.013	0.1	-9999	-0.24	29	29
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	0.015	0.095	-9999	-0.26	17	17
Syndecan-1/Syntenin	0.015	0.095	-9999	-0.26	17	17
MAPK3	0.018	0.088	-9999	-0.44	4	4
HGF/MET	-0.005	0.07	-9999	-0.28	17	17
TGFB1/TGF beta receptor Type II	0.01	0.001	-9999	-10000	0	0
BSG	0.01	0	-9999	-10000	0	0
keratinocyte migration	0.015	0.094	-9999	-0.26	17	17
Syndecan-1/RANTES	0.011	0.093	-9999	-0.26	18	18
Syndecan-1/CD147	0.019	0.093	-9999	-0.26	17	17
Syndecan-1/Syntenin/PIP2	0.012	0.091	-9999	-0.26	17	17
LAMA5	0.01	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	0.012	0.089	-9999	-0.25	17	17
MMP7	-0.001	0.058	-9999	-0.44	5	5
HGF	-0.017	0.11	-9999	-0.44	17	17
Syndecan-1/CASK	-0.021	0.081	-9999	-0.23	29	29
Syndecan-1/HGF/MET	0.005	0.11	-9999	-0.28	22	22
regulation of cell adhesion	0.018	0.086	-9999	-0.43	4	4
HPSE	-0.011	0.093	-9999	-0.44	13	13
positive regulation of cell migration	0.013	0.1	-9999	-0.24	29	29
SDC1	-0.001	0.094	-9999	-0.24	29	29
Syndecan-1/Collagen	0.013	0.1	-9999	-0.24	29	29
PPIB	0.01	0	-9999	-10000	0	0
MET	0.009	0.003	-9999	-10000	0	0
PRKACA	0.01	0	-9999	-10000	0	0
MMP9	0	0.052	-9999	-0.44	4	4
MAPK1	0.018	0.088	-9999	-0.44	4	4
homophilic cell adhesion	0.013	0.099	-9999	-0.24	29	29
MMP1	-0.019	0.11	-9999	-0.44	18	18

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.015	0	-10000	0	-10000	0	0
Necdin/E2F1	-0.014	0.083	-10000	0	-0.29	23	23
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.015	0.059	-10000	0	-0.23	15	15
NGF (dimer)/p75(NTR)/BEX1	-0.013	0.092	-10000	0	-0.26	34	34
NT-4/5 (dimer)/p75(NTR)	0.002	0.051	-10000	0	-0.3	8	8
IKBKB	0.01	0	-10000	0	-10000	0	0
AKT1	0.001	0.055	-10000	0	-0.23	15	15
IKBKG	0.01	0	-10000	0	-10000	0	0
BDNF	0.008	0.003	-10000	0	-10000	0	0
MGDIs/NGR/p75(NTR)/LINGO1	0.007	0.061	-10000	0	-0.28	12	12
FURIN	0.01	0	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	0.011	0.041	-10000	0	-0.23	8	8
LINGO1	0.002	0.059	-10000	0	-0.44	5	5
Sortilin/TRAF6/NRIF	0.012	0.012	-10000	0	-0.19	1	1
proBDNF (dimer)	0.008	0.003	-10000	0	-10000	0	0
NTRK1	-0.079	0.18	-10000	0	-0.44	56	56
RTN4R	0.01	0.001	-10000	0	-10000	0	0
neuron apoptosis	0.023	0.053	-10000	0	-0.38	1	1
IRAK1	0.01	0	-10000	0	-10000	0	0
SHC1	-0.004	0.064	-10000	0	-0.27	15	15
ARHGDIA	0.01	0	-10000	0	-10000	0	0
RhoA/GTP	0.007	0	-10000	0	-10000	0	0
Gamma Secretase	0.028	0.014	-10000	0	-0.22	1	1
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.011	0.062	-10000	0	-0.25	15	15
MAGEH1	0.01	0.001	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.009	0.1	-10000	0	-0.27	33	33
Mammalian IAPs/DIABLO	0.024	0.006	-10000	0	-10000	0	0
proNGF (dimer)	-0.003	0.074	-10000	0	-0.44	8	8
MAGED1	0.01	0	-10000	0	-10000	0	0
APP	0.01	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.005	0.005	-10000	0	-10000	0	0
ZNF274	0.01	0	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	0.005	0.056	-10000	0	-0.23	15	15
NGF	-0.003	0.074	-10000	0	-0.44	8	8
cell cycle arrest	0.004	0.058	0.2	1	-0.2	15	16
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.004	0.056	-10000	0	-0.23	15	15
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.008	0.044	-10000	0	-0.25	8	8
NCSTN	0.01	0	-10000	0	-10000	0	0
mol:GTP	0.004	0.066	-10000	0	-0.27	15	15
PSENEN	0.01	0	-10000	0	-10000	0	0
mol:ceramide	-0.001	0.059	-10000	0	-0.24	15	15
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.007	0.048	-10000	0	-0.37	1	1
p75(NTR)/beta APP	0.006	0.053	-10000	0	-0.31	8	8
BEX1	-0.02	0.11	-10000	0	-0.44	19	19
mol:GDP	-0.009	0.064	-10000	0	-0.28	15	15
NGF (dimer)	-0.12	0.13	-10000	0	-0.23	167	167
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.013	0.056	-10000	0	-0.25	12	12
PIK3R1	0.01	0	-10000	0	-10000	0	0
RAC1/GTP	0.004	0.057	-10000	0	-0.23	15	15
MYD88	0.01	0	-10000	0	-10000	0	0
CHUK	0.01	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	0.005	0.066	-10000	0	-0.27	15	15
RHOB	0.01	0	-10000	0	-10000	0	0
RHOA	0.01	0	-10000	0	-10000	0	0
MAGE-G1/E2F1	0.011	0.007	-10000	0	-10000	0	0
NT3 (dimer)	-0.039	0.14	-10000	0	-0.44	31	31
TP53	0.016	0.039	-10000	0	-0.2	5	5
PRDM4	-0.001	0.059	-10000	0	-0.25	15	15
BDNF (dimer)	-0.12	0.12	-10000	0	-0.22	156	156
PIK3CA	0.01	0	-10000	0	-10000	0	0
SORT1	0.01	0	-10000	0	-10000	0	0
activation of caspase activity	0.013	0.058	-10000	0	-0.23	15	15
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.011	0.062	-10000	0	-0.25	15	15
RHOC	0.01	0	-10000	0	-10000	0	0
XIAP	0.01	0	-10000	0	-10000	0	0
MAPK10	0.013	0.059	-10000	0	-0.28	5	5
DIABLO	0.01	0	-10000	0	-10000	0	0
SMPD2	-0.001	0.059	-10000	0	-0.25	15	15
APH1B	0.008	0.026	-10000	0	-0.44	1	1
APH1A	0.01	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	0.005	0.066	-10000	0	-0.27	15	15
PSEN1	0.01	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.015	0	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.029	0.12	-10000	0	-0.32	37	37
MAPK8	0.01	0.065	-10000	0	-0.28	5	5
MAPK9	0.013	0.059	-10000	0	-0.28	5	5
APAF1	0.01	0	-10000	0	-10000	0	0
NTF3	-0.039	0.14	-10000	0	-0.44	31	31
NTF4	0.005	0.005	-10000	0	-10000	0	0
NDN	-0.026	0.12	-10000	0	-0.44	23	23
RAC1/GDP	0.007	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	0.013	0.054	-10000	0	-0.21	15	15
p75 CTF/Sortilin/TRAF6/NRIF	0.025	0	-10000	0	-10000	0	0
RhoA-B-C/GTP	0.004	0.066	-10000	0	-0.27	15	15
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.019	0.037	-10000	0	-0.22	5	5
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.016	0.038	-10000	0	-0.2	8	8
PRKACB	0.01	0	-10000	0	-10000	0	0
proBDNF (dimer)/p75 ECD	0.013	0.005	-10000	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.009	0.002	-10000	0	-10000	0	0
BIRC2	0.01	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.009	0.088	0.15	18	-0.3	16	34
BAD	0.013	0.061	-10000	0	-0.29	5	5
RIPK2	0.01	0	-10000	0	-10000	0	0
NGFR	-0.003	0.074	-10000	0	-0.44	8	8
CYCS	0.001	0.055	-10000	0	-0.23	15	15
ADAM17	0.01	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.011	0.062	-10000	0	-0.25	15	15
BCL2L11	0.013	0.061	-10000	0	-0.26	8	8
BDNF (dimer)/p75(NTR)	0.005	0.048	-10000	0	-0.28	8	8
PI3K	0.011	0.061	-10000	0	-0.25	15	15
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.011	0.062	-10000	0	-0.25	15	15
NDNL2	0.01	0	-10000	0	-10000	0	0
YWHAE	0.01	0	-10000	0	-10000	0	0
PRKCI	0.01	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.003	0.077	-10000	0	-0.33	15	15
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.011	0.062	-10000	0	-0.25	15	15
TRAF6	0.01	0	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCZ	0.01	0	-10000	0	-10000	0	0
PLG	-0.25	0.22	-10000	0	-0.44	164	164
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	0	0.057	-10000	0	-0.24	14	14
SQSTM1	0.009	0.002	-10000	0	-10000	0	0
NGFRAP1	0.01	0	-10000	0	-10000	0	0
CASP3	0.013	0.058	-10000	0	-0.24	8	8
E2F1	0.007	0.004	-10000	0	-10000	0	0
CASP9	0.01	0	-10000	0	-10000	0	0
IKK complex	-0.024	0.099	-10000	0	-0.31	10	10
NGF (dimer)/TRKA	-0.058	0.14	-10000	0	-0.31	63	63
MMP7	-0.001	0.058	-10000	0	-0.44	5	5
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.015	0.059	-10000	0	-0.23	15	15
MMP3	0.002	0.004	-10000	0	-10000	0	0
APAF-1/Caspase 9	-0.009	0.04	-10000	0	-0.34	1	1

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.16	0.22	-9999	-0.44	109	109
HRAS	0.01	0	-9999	-10000	0	0
EGFR	0.01	0	-9999	-10000	0	0
AKT	0.017	0.015	-9999	-10000	0	0
FOXO3	0.01	0	-9999	-10000	0	0
AKT1	0.01	0	-9999	-10000	0	0
FOXO1	0.01	0	-9999	-10000	0	0
AKT3	0.01	0	-9999	-10000	0	0
FOXO4	0.01	0	-9999	-10000	0	0
MET	0.009	0.003	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
PIK3CB	0.01	0.001	-9999	-10000	0	0
NRAS	0.01	0	-9999	-10000	0	0
PIK3CG	0.007	0.037	-9999	-0.44	2	2
PIK3R3	0.01	0	-9999	-10000	0	0
PIK3R2	0.01	0	-9999	-10000	0	0
NF1	0.01	0	-9999	-10000	0	0
RAS	-0.035	0.07	-9999	-0.13	97	97
ERBB2	0.01	0	-9999	-10000	0	0
proliferation/survival/translation	-0.015	0.012	-9999	-10000	0	0
PI3K	-0.032	0.068	-9999	-0.12	96	96
PIK3R1	0.01	0	-9999	-10000	0	0
KRAS	0.01	0	-9999	-10000	0	0
FOXO	0.021	0.017	-9999	-10000	0	0
AKT2	0.01	0	-9999	-10000	0	0
PTEN	0.01	0	-9999	-10000	0	0

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.018	0.12	-9999	-0.41	24	24
KLHL20	0.006	0.045	-9999	-0.14	24	24
CYFIP2	0.008	0.026	-9999	-0.44	1	1
Rac1/GDP	0.001	0.073	-9999	-0.24	24	24
ENAH	-0.018	0.12	-9999	-0.41	24	24
AP1M1	0.01	0	-9999	-10000	0	0
RAP1B	0.01	0	-9999	-10000	0	0
RAP1A	0.01	0	-9999	-10000	0	0
CTNNB1	0.01	0	-9999	-10000	0	0
CDC42/GTP	0.002	0.052	-9999	-0.17	24	24
ABI1/Sra1/Nap1	-0.008	0.028	-9999	-0.19	1	1
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.004	0.071	-9999	-0.23	24	24
RAPGEF1	-0.014	0.1	-9999	-0.36	24	24
CTNND1	0.01	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.019	0.12	-9999	-0.42	24	24
CRK	-0.016	0.11	-9999	-0.38	24	24
E-cadherin/gamma catenin/alpha catenin	-0.003	0.077	-9999	-0.26	24	24
alphaE/beta7 Integrin	0.015	0	-9999	-10000	0	0
IQGAP1	0.01	0	-9999	-10000	0	0
NCKAP1	0.01	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.019	0	-9999	-10000	0	0
DLG1	-0.018	0.12	-9999	-0.41	24	24
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.011	0.035	-9999	-0.13	24	24
MLLT4	0.01	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.019	0.002	-9999	-10000	0	0
PI3K	-0.013	0.044	-9999	-0.16	24	24
ARF6	0.01	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.012	0.089	-9999	-0.31	24	24
TIAM1	0.01	0	-9999	-10000	0	0
E-cadherin(dimer)/Ca2+	0.003	0.066	-9999	-0.22	24	24
AKT1	0.004	0.03	-9999	-0.11	1	1
PIK3R1	0.01	0	-9999	-10000	0	0
CDH1	-0.027	0.12	-9999	-0.44	24	24
RhoA/GDP	0	0.073	-9999	-0.24	24	24
actin cytoskeleton organization	0.006	0.034	-9999	-0.2	1	1
CDC42/GDP	0	0.073	-9999	-0.24	24	24
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.008	0.064	-9999	-0.22	24	24
ITGB7	0.01	0	-9999	-10000	0	0
RAC1	0.01	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.004	0.071	-9999	-0.23	24	24
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.002	0.065	-9999	-0.22	24	24
mol:GDP	-0.006	0.082	-9999	-0.28	24	24
CDC42/GTP/IQGAP1	0.013	0	-9999	-10000	0	0
JUP	0.01	0	-9999	-10000	0	0
p120 catenin/RhoA/GDP	0.002	0.074	-9999	-0.25	24	24
RAC1/GTP/IQGAP1	0.013	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0.015	0	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
CDC42	0.01	0	-9999	-10000	0	0
CTNNA1	0.01	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.006	0.026	-9999	-0.23	1	1
NME1	0.01	0.001	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	-0.018	0.12	-9999	-0.41	24	24
regulation of cell-cell adhesion	-0.013	0.042	-9999	-0.15	24	24
WASF2	0.004	0.018	-9999	-0.1	1	1
Rap1/GTP	0.004	0.058	-9999	-0.19	24	24
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.009	0.068	-9999	-0.22	24	24
CCND1	0.006	0.031	-9999	-0.29	1	1
VAV2	-0.011	0.11	-9999	-0.38	24	24
RAP1/GDP	0.004	0.063	-9999	-0.21	24	24
adherens junction assembly	-0.017	0.11	-9999	-0.4	24	24
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.01	0	-9999	-10000	0	0
PIP5K1C	0.01	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.007	0.064	-9999	-0.21	24	24
E-cadherin/beta catenin	-0.019	0.09	-9999	-0.32	24	24
mol:GTP	0	0	-9999	-10000	0	0
SRC	-0.018	0.12	-9999	-0.41	24	24
PIK3CA	0.01	0	-9999	-10000	0	0
Rac1/GTP	-0.018	0.062	-9999	-0.22	24	24
E-cadherin/beta catenin/alpha catenin	-0.003	0.077	-9999	-0.26	24	24
ITGAE	0.01	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.02	0.12	-9999	-0.43	24	24

×

Coregulation of Androgen receptor activity

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
NRIP1	0.011	0.003	-10000	0	-10000	0	0
SVIL	0.011	0.003	-10000	0	-10000	0	0
ZNF318	0.007	0.007	-10000	0	-10000	0	0
JMJD2C	0.005	0.015	0.056	22	-10000	0	22
T-DHT/AR/Ubc9	-0.052	0.066	-10000	0	-0.28	12	12
CARM1	0.01	0	-10000	0	-10000	0	0
PRDX1	0.01	0	-10000	0	-10000	0	0
PELP1	0.009	0.001	-10000	0	-10000	0	0
CTNNB1	0.01	0.002	-10000	0	-10000	0	0
AKT1	0.009	0.004	-10000	0	-10000	0	0
PTK2B	0.01	0.002	-10000	0	-10000	0	0
MED1	0.009	0.003	-10000	0	-10000	0	0
MAK	0.007	0.007	-10000	0	-10000	0	0
response to oxidative stress	0	0.001	-10000	0	-10000	0	0
HIP1	0.008	0.037	-10000	0	-0.44	2	2
GSN	0.011	0.003	-10000	0	-10000	0	0
NCOA2	-0.03	0.13	-10000	0	-0.44	26	26
NCOA6	0.011	0.003	-10000	0	-10000	0	0
DNA-PK	0.017	0.008	-10000	0	-10000	0	0
NCOA4	0.01	0	-10000	0	-10000	0	0
PIAS3	0.01	0.002	-10000	0	-10000	0	0
cell proliferation	-0.027	0.025	-10000	0	-10000	0	0
XRCC5	0.009	0.003	-10000	0	-10000	0	0
UBE3A	0.011	0.004	-10000	0	-10000	0	0
T-DHT/AR/SNURF	-0.066	0.086	-10000	0	-0.29	27	27
FHL2	-0.04	0.063	-10000	0	-0.86	1	1
RANBP9	0.011	0.003	-10000	0	-10000	0	0
JMJD1A	-0.084	0.068	-10000	0	-0.14	186	186
CDK6	0.01	0	-10000	0	-10000	0	0
TGFB1I1	0.003	0.059	-10000	0	-0.44	5	5
T-DHT/AR/CyclinD1	-0.052	0.069	-10000	0	-0.28	13	13
XRCC6	0.009	0.003	-10000	0	-10000	0	0
T-DHT/AR	-0.097	0.099	-10000	0	-0.3	12	12
CTDSP1	0.01	0.001	-10000	0	-10000	0	0
CTDSP2	0.008	0.005	-10000	0	-10000	0	0
BRCA1	0.011	0.003	-10000	0	-10000	0	0
TCF4	0.008	0.004	-10000	0	-10000	0	0
CDKN2A	0.002	0.004	-10000	0	-10000	0	0
SRF	0.012	0.009	-10000	0	-0.14	1	1
NKX3-1	-0.14	0.11	-10000	0	-10000	0	0
KLK3	0.003	0.043	-10000	0	-10000	0	0
TMF1	0.01	0.001	-10000	0	-10000	0	0
HNRNPA1	0.009	0.004	-10000	0	-10000	0	0
AOF2	0.001	0.003	-10000	0	-10000	0	0
APPL1	0.008	0.005	-10000	0	-10000	0	0
T-DHT/AR/Caspase 8	-0.052	0.066	-10000	0	-0.28	12	12
AR	-0.051	0.091	-10000	0	-0.45	12	12
UBA3	0.01	0.001	-10000	0	-10000	0	0
PATZ1	0.009	0.004	-10000	0	-10000	0	0
PAWR	0.01	0.001	-10000	0	-10000	0	0
PRKDC	0.009	0.003	-10000	0	-10000	0	0
PA2G4	0.009	0.004	-10000	0	-10000	0	0
UBE2I	0.01	0	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.045	0.06	-10000	0	-0.25	12	12
RPS6KA3	0.011	0.003	-10000	0	-10000	0	0
T-DHT/AR/ARA70	-0.051	0.067	-10000	0	-0.28	12	12
LATS2	0.009	0.003	-10000	0	-10000	0	0
T-DHT/AR/PRX1	-0.046	0.06	-10000	0	-0.26	12	12
Cyclin D3/CDK11 p58	0.007	0.001	-10000	0	-10000	0	0
VAV3	0.009	0.026	-10000	0	-0.44	1	1
KLK2	-0.044	0.041	-10000	0	-10000	0	0
CASP8	0.01	0.001	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.063	0.099	-10000	0	-0.3	34	34
TMPRSS2	-0.54	0.41	-10000	0	-0.85	186	186
CCND1	0.009	0.026	-10000	0	-0.44	1	1
PIAS1	0.011	0.004	-10000	0	-10000	0	0
mol:T-DHT	-0.038	0.033	-10000	0	-0.065	171	171
CDC2L1	0	0	-10000	0	-10000	0	0
PIAS4	0.012	0.006	-10000	0	-10000	0	0
T-DHT/AR/CDK6	-0.052	0.066	-10000	0	-0.28	12	12
CMTM2	0.009	0.003	-10000	0	-10000	0	0
SNURF	-0.015	0.099	-10000	0	-0.44	15	15
ZMIZ1	-0.032	0.035	-10000	0	-10000	0	0
CCND3	0.01	0.001	-10000	0	-10000	0	0
TGIF1	0.009	0.004	-10000	0	-10000	0	0
FKBP4	0.011	0.003	-10000	0	-10000	0	0

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	0.033	0.091	0.26	25	-0.29	3	28
TBX21	0.077	0.23	0.61	17	-0.65	9	26
B2M	0.012	0.004	-10000	0	-10000	0	0
TYK2	0.02	0.03	0.15	3	-10000	0	3
IL12RB1	0.016	0.024	0.16	1	-10000	0	1
GADD45B	0.073	0.21	0.55	15	-0.59	10	25
IL12RB2	0.005	0.053	0.16	3	-0.45	3	6
GADD45G	0.071	0.22	0.59	11	-1	3	14
natural killer cell activation	0.012	0.029	0.13	7	-10000	0	7
RELB	0.01	0	-10000	0	-10000	0	0
RELA	0.01	0	-10000	0	-10000	0	0
IL18	0.014	0.013	-10000	0	-10000	0	0
IL2RA	0.009	0.003	-10000	0	-10000	0	0
IFNG	0.006	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	0.058	0.19	0.46	19	-0.57	9	28
HLA-DRB5	0.003	0.039	-10000	0	-0.45	2	2
FASLG	0.081	0.24	0.63	17	-0.65	9	26
NF kappa B2 p52/RelB	-0.003	0.15	-10000	0	-0.64	9	9
CD4	0.006	0.01	-10000	0	-10000	0	0
SOCS1	0.007	0.037	-10000	0	-0.44	2	2
EntrezGene:6955	-0.001	0.01	-10000	0	-10000	0	0
CD3D	0.005	0.011	-10000	0	-10000	0	0
CD3E	0.005	0.029	-10000	0	-0.45	1	1
CD3G	0.006	0.012	-10000	0	-10000	0	0
IL12Rbeta2/JAK2	0.013	0.053	0.22	6	-0.33	3	9
CCL3	0.08	0.25	0.58	22	-0.7	9	31
CCL4	0.08	0.24	0.63	17	-0.65	9	26
HLA-A	0.012	0.004	-10000	0	-10000	0	0
IL18/IL18R	0.042	0.052	0.2	11	-0.25	1	12
NOS2	0.024	0.36	0.59	15	-1.1	22	37
IL12/IL12R/TYK2/JAK2/SPHK2	0.034	0.088	0.26	24	-0.3	2	26
IL1R1	0.074	0.23	0.61	13	-0.65	9	22
IL4	-0.01	0.029	-10000	0	-0.13	7	7
JAK2	0.02	0.03	0.13	7	-10000	0	7
EntrezGene:6957	-0.001	0.009	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	0.015	0.033	-10000	0	-10000	0	0
RAB7A	0.079	0.2	0.54	12	-0.62	3	15
lysosomal transport	0.079	0.19	0.52	14	-0.59	3	17
FOS	-0.092	0.46	0.47	11	-1.1	44	55
STAT4 (dimer)	0.088	0.21	0.49	25	-0.57	9	34
STAT5A (dimer)	-0.021	0.15	-10000	0	-0.64	9	9
GZMA	0.079	0.22	0.61	16	-0.61	9	25
GZMB	0.077	0.22	0.62	14	-0.61	9	23
HLX	0.01	0.001	-10000	0	-10000	0	0
LCK	0.074	0.24	0.55	25	-0.68	9	34
TCR/CD3/MHC II/CD4	-0.013	0.083	-10000	0	-0.21	32	32
IL2/IL2R	0.017	0.008	-10000	0	-10000	0	0
MAPK14	0.078	0.22	0.55	15	-0.58	11	26
CCR5	0.082	0.22	0.57	22	-0.54	9	31
IL1B	0.012	0.067	0.15	3	-0.44	5	8
STAT6	0.045	0.097	0.28	21	-0.23	2	23
STAT4	0.009	0.003	-10000	0	-10000	0	0
STAT3	0.01	0	-10000	0	-10000	0	0
STAT1	0.01	0.001	-10000	0	-10000	0	0
NFKB1	0.01	0	-10000	0	-10000	0	0
NFKB2	0.01	0	-10000	0	-10000	0	0
IL12B	0.016	0.029	0.16	2	-10000	0	2
CD8A	0.01	0.004	-10000	0	-10000	0	0
CD8B	0.01	0.004	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.033	0.091	0.29	3	-0.26	25	28
IL2RB	0.009	0.003	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.089	0.2	0.49	25	-0.53	9	34
IL2RG	0.009	0.002	-10000	0	-10000	0	0
IL12	0.03	0.048	0.2	11	-10000	0	11
STAT5A	0.01	0	-10000	0	-10000	0	0
CD247	0.007	0.011	-10000	0	-10000	0	0
IL2	0.003	0.005	-10000	0	-10000	0	0
SPHK2	0.01	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.019	0.03	0.16	1	-10000	0	1
IL12/IL12R/TYK2/JAK2	0.034	0.2	0.56	5	-0.72	9	14
MAP2K3	0.076	0.22	0.52	19	-0.58	10	29
RIPK2	0.01	0	-10000	0	-10000	0	0
MAP2K6	0.076	0.22	0.53	17	-0.58	10	27
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.004	0.029	-10000	0	-0.45	1	1
IL18RAP	0.01	0.012	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	0.023	0.033	0.17	3	-10000	0	3
EOMES	0.001	0.04	-10000	0	-10000	0	0
STAT1 (dimer)	0.051	0.18	0.44	15	-0.55	9	24
T cell proliferation	0.077	0.19	0.45	24	-0.47	9	33
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.012	0.029	-10000	0	-0.44	1	1
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.042	0.12	-10000	0	-0.48	15	15
ATF2	0.076	0.21	0.5	17	-0.54	11	28

×

EPHB forward signaling

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
Ephrin A5/EPHB2	-0.007	0.071	-10000	0	-0.26	21	21
cell-cell adhesion	0.008	0.036	0.18	12	-10000	0	12
Ephrin B/EPHB2/RasGAP	0.018	0.045	-10000	0	-0.22	10	10
ITSN1	0.01	0	-10000	0	-10000	0	0
PIK3CA	0.01	0	-10000	0	-10000	0	0
SHC1	0.01	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.063	0.12	-10000	0	-0.26	81	81
Ephrin B1/EPHB1	0.01	0.028	-10000	0	-0.26	3	3
HRAS/GDP	0.003	0.039	-10000	0	-0.22	6	6
Ephrin B/EPHB1/GRB7	0.015	0.05	-10000	0	-0.21	13	13
Endophilin/SYNJ1	0.01	0.044	-10000	0	-0.2	10	10
KRAS	0.01	0	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	0.015	0.05	-10000	0	-0.21	13	13
endothelial cell migration	0.021	0	-10000	0	-10000	0	0
GRB2	0.01	0	-10000	0	-10000	0	0
GRB7	0.01	0	-10000	0	-10000	0	0
PAK1	0.012	0.045	-10000	0	-0.2	10	10
HRAS	0.01	0	-10000	0	-10000	0	0
RRAS	0.011	0.045	-10000	0	-0.2	10	10
DNM1	0.005	0.027	-10000	0	-0.44	1	1
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	0.009	0.049	-10000	0	-0.2	13	13
lamellipodium assembly	-0.008	0.036	-10000	0	-0.18	12	12
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.01	0.044	-10000	0	-0.19	12	12
PIK3R1	0.01	0	-10000	0	-10000	0	0
EPHB2	0.01	0.001	-10000	0	-10000	0	0
EPHB3	-0.12	0.2	-10000	0	-0.44	81	81
EPHB1	0.005	0.046	-10000	0	-0.44	3	3
EPHB4	0.01	0	-10000	0	-10000	0	0
mol:GDP	0.037	0.068	0.17	8	-0.23	6	14
Ephrin B/EPHB2	0.013	0.044	-10000	0	-0.22	10	10
Ephrin B/EPHB3	-0.052	0.11	-10000	0	-0.22	88	88
JNK cascade	0.013	0.026	-10000	0	-0.21	3	3
Ephrin B/EPHB1	0.01	0.049	-10000	0	-0.21	13	13
RAP1/GDP	0.044	0.061	0.16	1	-0.21	6	7
EFNB2	0.01	0	-10000	0	-10000	0	0
EFNB3	-0.007	0.082	-10000	0	-0.44	10	10
EFNB1	0.01	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	0.016	0.026	-10000	0	-0.23	3	3
RAP1B	0.01	0	-10000	0	-10000	0	0
RAP1A	0.01	0	-10000	0	-10000	0	0
CDC42/GTP	0.012	0.048	-10000	0	-0.22	9	9
Rap1/GTP	0.003	0.039	-10000	0	-0.18	12	12
axon guidance	-0.007	0.071	-10000	0	-0.26	21	21
MAPK3	0.011	0.039	-10000	0	-0.19	3	3
MAPK1	0.011	0.039	-10000	0	-0.19	3	3
Rac1/GDP	0.042	0.064	0.17	8	-0.22	6	14
actin cytoskeleton reorganization	-0.006	0.03	-10000	0	-10000	0	0
CDC42/GDP	0.042	0.064	0.17	8	-0.22	6	14
PI3K	0.023	0	-10000	0	-10000	0	0
EFNA5	-0.023	0.12	-10000	0	-0.44	21	21
Ephrin B2/EPHB4	0.013	0	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	0.008	0.042	-10000	0	-0.21	10	10
CDC42	0.01	0	-10000	0	-10000	0	0
RAS family/GTP	-0.008	0.036	-10000	0	-10000	0	0
PTK2	0.004	0.005	-10000	0	-10000	0	0
MAP4K4	0.013	0.026	-10000	0	-0.22	3	3
SRC	0.01	0.001	-10000	0	-10000	0	0
KALRN	0.01	0	-10000	0	-10000	0	0
Intersectin/N-WASP	0.015	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.018	0.045	-10000	0	-0.19	9	9
MAP2K1	0.01	0.041	-10000	0	-0.18	12	12
WASL	0.01	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	0.022	0.026	-10000	0	-0.23	3	3
cell migration	0.019	0.052	-10000	0	-0.21	13	13
NRAS	0.01	0	-10000	0	-10000	0	0
SYNJ1	0.011	0.045	-10000	0	-0.2	10	10
PXN	0.01	0	-10000	0	-10000	0	0
TF	0.007	0.048	-10000	0	-0.2	13	13
HRAS/GTP	0.011	0.043	-10000	0	-0.19	12	12
Ephrin B1/EPHB1-2	0.016	0.026	-10000	0	-0.23	3	3
cell adhesion mediated by integrin	0.026	0.065	0.25	10	-10000	0	10
RAC1	0.01	0	-10000	0	-10000	0	0
mol:GTP	0.013	0.046	-10000	0	-0.2	12	12
RAC1-CDC42/GTP	-0.056	0.088	-10000	0	-0.19	79	79
RASA1	0.01	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0.044	0.061	0.16	8	-0.21	6	14
ruffle organization	0.015	0.046	-10000	0	-0.18	12	12
NCK1	0.01	0	-10000	0	-10000	0	0
receptor internalization	0.003	0.041	-10000	0	-0.2	10	10
Ephrin B/EPHB2/KALRN	0.018	0.045	-10000	0	-0.22	10	10
ROCK1	-0.058	0.11	-10000	0	-0.23	81	81
RAS family/GDP	-0.006	0.03	-10000	0	-0.18	6	6
Rac1/GTP	-0.008	0.038	-10000	0	-0.19	12	12
Ephrin B/EPHB1/Src/Paxillin	0.005	0.047	-10000	0	-0.21	13	13

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.088	0.073	-10000	0	-0.37	2	2
epithelial cell differentiation	-0.098	0.097	-10000	0	-0.23	86	86
ITCH	0.034	0.016	-10000	0	-10000	0	0
WWP1	-0.076	0.06	-10000	0	-10000	0	0
FYN	0.01	0	-10000	0	-10000	0	0
EGFR	0.01	0	-10000	0	-10000	0	0
PRL	0.001	0.003	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.046	0.048	-10000	0	-0.26	2	2
PTPRZ1	-0.003	0.058	-10000	0	-0.44	5	5
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.049	0.055	-10000	0	-0.28	2	2
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.067	0.058	-10000	0	-0.27	5	5
ADAM17	0.034	0.016	-10000	0	-10000	0	0
ErbB4/ErbB4	-0.1	0.079	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.088	0.074	-10000	0	-0.37	3	3
NCOR1	0.01	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.059	0.056	-10000	0	-0.25	5	5
GRIN2B	-0.055	0.053	-10000	0	-0.29	2	2
ErbB4/ErbB2/betacellulin	-0.064	0.07	-10000	0	-0.3	12	12
STAT1	0.01	0.001	-10000	0	-10000	0	0
HBEGF	0.007	0.037	-10000	0	-0.44	2	2
PRLR	-0.16	0.22	-10000	0	-0.44	111	111
E4ICDs/ETO2	-0.086	0.069	-10000	0	-10000	0	0
axon guidance	-0.035	0.036	-10000	0	-10000	0	0
NEDD4	0.034	0.016	-10000	0	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	-0.11	0.16	-10000	0	-0.31	111	111
CBFA2T3	0.01	0.001	-10000	0	-10000	0	0
ErbB4/ErbB2/HBEGF	-0.057	0.054	-10000	0	-0.31	2	2
MAPK3	-0.048	0.05	-10000	0	-0.27	2	2
STAT1 (dimer)	-0.085	0.069	-10000	0	-10000	0	0
MAPK1	-0.048	0.05	-10000	0	-0.27	2	2
JAK2	0.01	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.06	0.054	-10000	0	-0.25	5	5
NRG1	0.019	0.045	-10000	0	-0.31	5	5
NRG3	0.004	0.046	-10000	0	-0.44	3	3
NRG2	0.005	0.046	-10000	0	-0.44	3	3
NRG4	0.007	0.026	-10000	0	-0.44	1	1
heart development	-0.035	0.036	-10000	0	-10000	0	0
neural crest cell migration	-0.06	0.054	-10000	0	-0.25	5	5
ERBB2	0.024	0.01	-10000	0	-10000	0	0
WWOX/E4ICDs	-0.086	0.069	-10000	0	-10000	0	0
SHC1	0.01	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.077	0.067	-10000	0	-0.34	1	1
apoptosis	0.067	0.062	0.4	3	-10000	0	3
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.089	0.072	-10000	0	-0.28	3	3
ErbB4/ErbB2/epiregulin	-0.031	0.042	-10000	0	-10000	0	0
ErbB4/ErbB4/betacellulin/betacellulin	-0.096	0.088	-10000	0	-0.36	12	12
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.15	0.12	-10000	0	-0.29	107	107
MDM2	-0.088	0.067	-10000	0	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.043	0.046	-10000	0	-0.25	5	5
STAT5A	-0.03	0.036	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.059	0.056	-10000	0	-0.25	5	5
DLG4	0.01	0	-10000	0	-10000	0	0
GRB2/SHC	0.015	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.079	0.063	-10000	0	-10000	0	0
STAT5A (dimer)	-0.1	0.1	-10000	0	-0.24	86	86
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.029	0.038	-10000	0	-10000	0	0
LRIG1	0.01	0.001	-10000	0	-10000	0	0
EREG	0.005	0.005	-10000	0	-10000	0	0
BTC	-0.009	0.09	-10000	0	-0.44	12	12
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.036	0.036	-10000	0	-10000	0	0
ERBB4	-0.1	0.079	-10000	0	-10000	0	0
STAT5B	0.01	0	-10000	0	-10000	0	0
YAP1	-0.025	0.023	-10000	0	-10000	0	0
GRB2	0.01	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.056	0.052	-10000	0	-0.31	1	1
glial cell differentiation	0.078	0.063	-10000	0	-10000	0	0
WWOX	0.01	0	-10000	0	-10000	0	0
cell proliferation	-0.046	0.067	-10000	0	-0.29	13	13

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.009	0.058	-9999	-0.21	17	17
NF kappa B1 p50/RelA/I kappa B alpha	0.015	0.064	-9999	-0.22	2	2
alphaV/beta3 Integrin/Osteopontin/Src	0.013	0.034	-9999	-0.31	3	3
AP1	-0.014	0.11	-9999	-0.36	14	14
ILK	0.004	0.059	-9999	-0.22	17	17
bone resorption	0.007	0.062	-9999	-0.38	2	2
PTK2B	0.01	0	-9999	-10000	0	0
PYK2/p130Cas	0.016	0.057	-9999	-0.2	18	18
ITGAV	0.01	0.006	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.008	0.042	-9999	-0.31	5	5
alphaV/beta3 Integrin/Osteopontin	0.008	0.067	-9999	-0.25	17	17
MAP3K1	0.004	0.06	-9999	-0.23	17	17
JUN	0.01	0.001	-9999	-10000	0	0
MAPK3	0.004	0.063	-9999	-0.2	22	22
MAPK1	0.004	0.063	-9999	-0.2	22	22
Rac1/GDP	0.007	0	-9999	-10000	0	0
NFKB1	0.01	0	-9999	-10000	0	0
MAPK8	0.002	0.069	-9999	-0.23	20	20
ITGB3	-0.011	0.096	-9999	-0.44	14	14
NFKBIA	0.005	0.066	-9999	-0.24	5	5
FOS	-0.058	0.16	-9999	-0.44	44	44
CD44	0.009	0.002	-9999	-10000	0	0
CHUK	0.01	0	-9999	-10000	0	0
PLAU	-0.014	0.17	-9999	-1	7	7
NF kappa B1 p50/RelA	0.013	0.066	-9999	-0.28	5	5
BCAR1	0.01	0	-9999	-10000	0	0
RELA	0.01	0	-9999	-10000	0	0
alphaV beta3 Integrin	0.001	0.07	-9999	-0.31	14	14
mol:GDP	0	0	-9999	-10000	0	0
SYK	0.003	0.061	-9999	-0.23	18	18
VAV3	0.003	0.06	-9999	-0.21	19	19
MAP3K14	0.004	0.061	-9999	-0.23	17	17
ROCK2	0.002	0.059	-9999	-0.44	5	5
SPP1	0.005	0.046	-9999	-0.44	3	3
RAC1	0.01	0	-9999	-10000	0	0
Rac1/GTP	0.007	0.054	-9999	-0.19	19	19
MMP2	-0.018	0.096	-9999	-0.31	14	14

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.025	0.12	-9999	-0.44	22	22
GNB1/GNG2	0.015	0.059	-9999	-0.19	20	20
mol:DAG	0.012	0.055	-9999	-0.18	1	1
PLCG1	0.012	0.056	-9999	-0.18	1	1
YES1	-0.003	0.056	-9999	-0.2	20	20
FZD3	0.01	0	-9999	-10000	0	0
FZD6	0.01	0	-9999	-10000	0	0
G protein	0.016	0.057	-9999	-10000	0	0
MAP3K7	-0.066	0.1	-9999	-0.33	6	6
mol:Ca2+	0.011	0.054	-9999	-0.18	1	1
mol:IP3	0.012	0.055	-9999	-0.18	1	1
NLK	0.004	0.007	-9999	-10000	0	0
GNB1	0.01	0	-9999	-10000	0	0
CAMK2A	-0.071	0.11	-9999	-0.2	94	94
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.003	0.06	-9999	-0.22	20	20
CSNK1A1	0.01	0	-9999	-10000	0	0
GNAS	-0.003	0.056	-9999	-0.2	20	20
GO:0007205	0.01	0.053	-9999	-10000	0	0
WNT6	0.007	0.026	-9999	-0.44	1	1
WNT4	-0.004	0.078	-9999	-0.44	9	9
NFAT1/CK1 alpha	0	0.078	-9999	-0.37	1	1
GNG2	0.01	0	-9999	-10000	0	0
WNT5A	0.008	0.003	-9999	-10000	0	0
WNT11	-0.009	0.09	-9999	-0.44	12	12
CDC42	-0.002	0.053	-9999	-0.19	20	20

×

S1P5 pathway

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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.003	0.063	0.19	30	-10000	0	30
GNAI2	0.01	0	-10000	0	-10000	0	0
S1P/S1P5/G12	0.01	0.028	-10000	0	-0.26	3	3
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.029	0.13	-10000	0	-0.44	25	25
RhoA/GTP	-0.003	0.064	-10000	0	-0.19	30	30
negative regulation of cAMP metabolic process	-0.008	0.069	-10000	0	-0.21	30	30
GNAZ	0.01	0	-10000	0	-10000	0	0
GNAI3	0.01	0	-10000	0	-10000	0	0
GNA12	0.01	0	-10000	0	-10000	0	0
S1PR5	0.005	0.046	-10000	0	-0.44	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.009	0.069	-10000	0	-0.21	30	30
RhoA/GDP	0.007	0	-10000	0	-10000	0	0
RHOA	0.01	0	-10000	0	-10000	0	0
GNAI1	0.007	0.037	-10000	0	-0.44	2	2

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.029	0.13	-9999	-0.44	25	25
CDC42/GTP	-0.001	0.061	-9999	-0.19	27	27
PLCG1	-0.005	0.062	-9999	-0.2	27	27
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.01	0	-9999	-10000	0	0
GNAI3	0.01	0	-9999	-10000	0	0
G12/G13	0.015	0.001	-9999	-10000	0	0
cell migration	-0.001	0.06	-9999	-0.19	27	27
S1PR5	0.005	0.046	-9999	-0.44	3	3
S1PR4	0.01	0.001	-9999	-10000	0	0
MAPK3	-0.005	0.062	-9999	-0.2	27	27
MAPK1	-0.005	0.062	-9999	-0.2	27	27
S1P/S1P5/Gi	-0.009	0.069	-9999	-0.21	30	30
GNAI1	0.007	0.037	-9999	-0.44	2	2
CDC42/GDP	0.007	0	-9999	-10000	0	0
S1P/S1P5/G12	0.01	0.028	-9999	-0.26	3	3
RHOA	0.013	0.01	-9999	-10000	0	0
S1P/S1P4/Gi	-0.006	0.066	-9999	-0.21	27	27
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	0.01	0	-9999	-10000	0	0
S1P/S1P4/G12/G13	0.019	0.003	-9999	-10000	0	0
GNA12	0.01	0	-9999	-10000	0	0
GNA13	0.01	0.001	-9999	-10000	0	0
CDC42	0.01	0	-9999	-10000	0	0

×

Regulation of nuclear SMAD2/3 signaling

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
EP300	0.007	0.009	-10000	0	-10000	0	0
HSPA8	0.009	0.026	-10000	0	-0.43	1	1
SMAD3/SMAD4/ER alpha	0.004	0.073	-10000	0	-0.27	17	17
AKT1	0.012	0.003	-10000	0	-10000	0	0
GSC	0.017	0.028	-10000	0	-10000	0	0
NKX2-5	0.002	0.004	-10000	0	-10000	0	0
muscle cell differentiation	-0.02	0.02	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1	0.043	0.03	-10000	0	-10000	0	0
SMAD4	0.013	0.018	-10000	0	-10000	0	0
CBFB	0.01	0	-10000	0	-10000	0	0
SAP18	0.01	0.001	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.016	0.012	-10000	0	-10000	0	0
SMAD3/SMAD4/VDR	0.026	0.04	-10000	0	-0.22	5	5
MYC	0.008	0.006	-10000	0	-10000	0	0
CDKN2B	0.022	0.027	-10000	0	-10000	0	0
AP1	-0.001	0.085	-10000	0	-0.21	33	33
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.029	0.007	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.024	0.016	-10000	0	-10000	0	0
SP3	0.01	0	-10000	0	-10000	0	0
CREB1	0.01	0	-10000	0	-10000	0	0
FOXH1	0.01	0.004	-10000	0	-10000	0	0
SMAD3/SMAD4/GR	0.024	0.027	-10000	0	-10000	0	0
GATA3	-0.33	0.19	-10000	0	-0.43	225	225
SKI/SIN3/HDAC complex/NCoR1	0.022	0.005	-10000	0	-10000	0	0
MEF2C/TIF2	0.014	0.061	-10000	0	-10000	0	0
endothelial cell migration	0.048	0.25	1.2	13	-10000	0	13
MAX	0.011	0.011	-10000	0	-10000	0	0
RBBP7	0.01	0.001	-10000	0	-10000	0	0
RBBP4	0.01	0.001	-10000	0	-10000	0	0
RUNX2	0.01	0.001	-10000	0	-10000	0	0
RUNX3	0.008	0.003	-10000	0	-10000	0	0
RUNX1	0.009	0.003	-10000	0	-10000	0	0
CTBP1	0.01	0	-10000	0	-10000	0	0
NR3C1	0.011	0.011	-10000	0	-10000	0	0
VDR	0.002	0.059	-10000	0	-0.44	5	5
CDKN1A	0.028	0.031	-10000	0	-10000	0	0
KAT2B	0.009	0.005	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	0.03	0.017	-10000	0	-10000	0	0
DCP1A	0.01	0	-10000	0	-10000	0	0
SKI	0.01	0.001	-10000	0	-10000	0	0
SERPINE1	-0.048	0.26	-10000	0	-1.2	13	13
SMAD3/SMAD4/ATF2	0.023	0.024	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	0.01	0.067	-10000	0	-0.28	13	13
SAP30	0.01	0.001	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.016	0.015	-10000	0	-10000	0	0
JUN	-0.006	0.082	-10000	0	-0.2	33	33
SMAD3/SMAD4/IRF7	0.024	0.024	-10000	0	-10000	0	0
TFE3	0.01	0.015	-10000	0	-10000	0	0
COL1A2	0.015	0.025	-10000	0	-10000	0	0
mesenchymal cell differentiation	-0.022	0.024	-10000	0	-10000	0	0
DLX1	0.008	0.004	-10000	0	-10000	0	0
TCF3	0.01	0	-10000	0	-10000	0	0
FOS	-0.056	0.16	-10000	0	-0.44	44	44
SMAD3/SMAD4/Max	0.024	0.027	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.018	0.009	-10000	0	-10000	0	0
ZBTB17	0.008	0.005	-10000	0	-10000	0	0
LAMC1	0.02	0.023	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.023	0.024	-10000	0	-10000	0	0
IRF7	0.011	0.004	-10000	0	-10000	0	0
ESR1	-0.018	0.11	-10000	0	-0.44	17	17
HNF4A	-0.038	0.14	-10000	0	-0.44	31	31
MEF2C	0.03	0.026	-10000	0	-10000	0	0
SMAD2-3/SMAD4	0.027	0.024	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.017	0.011	-10000	0	-10000	0	0
IGHV3OR16-13	0.005	0.005	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.01	0	-10000	0	-10000	0	0
CREBBP	0.008	0.007	-10000	0	-10000	0	0
SKIL	0.01	0	-10000	0	-10000	0	0
HDAC1	0.01	0.001	-10000	0	-10000	0	0
HDAC2	0.01	0.001	-10000	0	-10000	0	0
SNIP1	0.01	0.001	-10000	0	-10000	0	0
GCN5L2	-0.001	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.028	0.028	-10000	0	-10000	0	0
MSG1/HSC70	0.014	0.019	-10000	0	-0.3	1	1
SMAD2	0.013	0.004	-10000	0	-10000	0	0
SMAD3	0.012	0.019	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.022	0.016	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.005	0.011	-10000	0	-10000	0	0
NCOR1	0.01	0.001	-10000	0	-10000	0	0
NCOA2	-0.031	0.13	-10000	0	-0.44	26	26
NCOA1	0.01	0	-10000	0	-10000	0	0
MYOD/E2A	0.008	0.003	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.048	0.031	-10000	0	-10000	0	0
IFNB1	0.014	0.02	-10000	0	-10000	0	0
SMAD3/SMAD4/MEF2C	0.037	0.028	-10000	0	-10000	0	0
CITED1	0.009	0.002	-10000	0	-10000	0	0
SMAD2-3/SMAD4/ARC105	0.032	0.024	-10000	0	-10000	0	0
RBL1	0.01	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.029	0.018	-10000	0	-10000	0	0
RUNX1-3/PEBPB2	0.016	0.008	-10000	0	-10000	0	0
SMAD7	0.008	0.085	-10000	0	-10000	0	0
MYC/MIZ-1	0.011	0.009	-10000	0	-10000	0	0
SMAD3/SMAD4	-0.008	0.09	-10000	0	-0.41	13	13
IL10	-0.16	0.11	-10000	0	-0.24	198	198
PIASy/HDAC complex	0.011	0.006	-10000	0	-10000	0	0
PIAS3	0.009	0.005	-10000	0	-10000	0	0
CDK2	0.008	0.006	-10000	0	-10000	0	0
IL5	-0.17	0.11	-10000	0	-0.24	198	198
CDK4	0.008	0.007	-10000	0	-10000	0	0
PIAS4	0.011	0.006	-10000	0	-10000	0	0
ATF3	-0.01	0.093	-10000	0	-0.44	13	13
SMAD3/SMAD4/SP1	0.032	0.029	-10000	0	-10000	0	0
FOXG1	0.002	0.005	-10000	0	-10000	0	0
FOXO3	0.012	0.005	-10000	0	-10000	0	0
FOXO1	0.012	0.004	-10000	0	-10000	0	0
FOXO4	0.012	0.004	-10000	0	-10000	0	0
heart looping	0.03	0.026	-10000	0	-10000	0	0
CEBPB	0.01	0.003	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	0.021	0.023	-10000	0	-10000	0	0
MYOD1	0.001	0.003	-10000	0	-10000	0	0
SMAD3/SMAD4/HNF4	-0.007	0.092	-10000	0	-0.27	31	31
SMAD3/SMAD4/GATA3	-0.2	0.13	-10000	0	-0.27	209	209
SnoN/SIN3/HDAC complex/NCoR1	0.01	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.025	0.025	-10000	0	-10000	0	0
SMAD3/SMAD4/SP1-3	0.04	0.029	-10000	0	-10000	0	0
MED15	0.01	0	-10000	0	-10000	0	0
SP1	0.015	0.008	-10000	0	-10000	0	0
SIN3B	0.01	0.001	-10000	0	-10000	0	0
SIN3A	0.01	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.03	0.017	-10000	0	-10000	0	0
ITGB5	0.027	0.025	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.021	0.003	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	0.011	0.063	-10000	0	-0.27	12	12
AR	-0.009	0.09	-10000	0	-0.44	12	12
negative regulation of cell growth	0.018	0.038	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	0.016	0.021	-10000	0	-10000	0	0
E2F5	0.01	0	-10000	0	-10000	0	0
E2F4	0.01	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.035	0.017	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4	0.026	0.016	-10000	0	-10000	0	0
TFDP1	0.01	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.005	0.087	-10000	0	-0.21	33	33
SMAD3/SMAD4/RUNX2	0.022	0.024	-10000	0	-10000	0	0
TGIF2	0.01	0	-10000	0	-10000	0	0
TGIF1	0.01	0	-10000	0	-10000	0	0
ATF2	0.01	0	-10000	0	-10000	0	0

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0.001	0.06	-10000	0	-10000	0	0
HDAC1	0.008	0.003	-10000	0	-10000	0	0
AES	0.009	0.001	-10000	0	-10000	0	0
FBXW11	0.01	0	-10000	0	-10000	0	0
DTX1	0	0.064	-10000	0	-0.44	6	6
LRP6/FZD1	0.014	0.003	-10000	0	-10000	0	0
TLE1	0.009	0.001	-10000	0	-10000	0	0
AP1	-0.1	0.15	-10000	0	-0.27	113	113
NCSTN	0.01	0	-10000	0	-10000	0	0
ADAM10	0.01	0.001	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.028	0.031	-10000	0	-10000	0	0
NICD/RBPSUH	0.019	0.004	-10000	0	-10000	0	0
WIF1	0.006	0.005	-10000	0	-10000	0	0
NOTCH1	0.014	0.004	-10000	0	-10000	0	0
PSENEN	0.01	0	-10000	0	-10000	0	0
KREMEN2	0.008	0.004	-10000	0	-10000	0	0
DKK1	0.008	0.004	-10000	0	-10000	0	0
beta catenin/beta TrCP1	0.055	0.061	0.16	10	-10000	0	10
APH1B	0.008	0.026	-10000	0	-0.44	1	1
APH1A	0.01	0	-10000	0	-10000	0	0
AXIN1	-0.008	0.021	-10000	0	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	0.007	0.029	-10000	0	-0.22	4	4
PSEN1	0.01	0	-10000	0	-10000	0	0
FOS	-0.058	0.16	-10000	0	-0.44	44	44
JUN	0.01	0	-10000	0	-10000	0	0
MAP3K7	0.009	0.001	-10000	0	-10000	0	0
CTNNB1	0.053	0.066	0.17	10	-10000	0	10
MAPK3	0.01	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.016	0.017	-10000	0	-0.26	1	1
HNF1A	0.003	0.052	-10000	0	-0.44	4	4
CTBP1	0.009	0.001	-10000	0	-10000	0	0
MYC	0.015	0.023	-10000	0	-10000	0	0
NKD1	-0.12	0.2	-10000	0	-0.44	82	82
FZD1	0.01	0.002	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	0.014	0.032	-10000	0	-10000	0	0
apoptosis	-0.1	0.15	-10000	0	-0.27	113	113
Delta 1/NOTCHprecursor	0.001	0.06	-10000	0	-10000	0	0
DLL1	-0.026	0.12	-10000	0	-0.44	23	23
PPARD	0.013	0.007	-10000	0	-10000	0	0
Gamma Secretase	0.029	0.014	-10000	0	-0.22	1	1
APC	-0.008	0.021	-10000	0	-10000	0	0
DVL1	0.013	0.005	-10000	0	-10000	0	0
CSNK2A1	0.01	0	-10000	0	-10000	0	0
MAP3K7IP1	-0.001	0.001	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	0.015	0.007	-10000	0	-10000	0	0
LRP6	0.01	0	-10000	0	-10000	0	0
CSNK1A1	0.01	0	-10000	0	-10000	0	0
NLK	0.006	0.003	-10000	0	-10000	0	0
CCND1	0.009	0.074	-10000	0	-1.2	1	1
WNT1	0.008	0.004	-10000	0	-10000	0	0
Axin1/APC/beta catenin	0.043	0.035	-10000	0	-10000	0	0
DKK2	0.008	0.026	-10000	0	-0.44	1	1
NOTCH1 precursor/DVL1	0.026	0.007	-10000	0	-10000	0	0
GSK3B	0.01	0	-10000	0	-10000	0	0
FRAT1	0.009	0.001	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	0.015	0.032	-10000	0	-10000	0	0
PPP2R5D	0.074	0.1	0.24	82	-10000	0	82
MAPK1	0.01	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.019	0.009	-10000	0	-10000	0	0
RBPJ	0.01	0	-10000	0	-10000	0	0
CREBBP	0.011	0.001	-10000	0	-10000	0	0

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.009	0.002	-10000	0	-10000	0	0
MAP4K4	0.014	0.02	-10000	0	-10000	0	0
BAG4	0.01	0	-10000	0	-10000	0	0
PKC zeta/ceramide	-0.061	0.024	-10000	0	-0.12	9	9
NFKBIA	0.01	0	-10000	0	-10000	0	0
BIRC3	0.009	0.002	-10000	0	-10000	0	0
BAX	-0.026	0.011	-10000	0	-10000	0	0
RIPK1	0.01	0	-10000	0	-10000	0	0
AKT1	0.016	0.004	-10000	0	-10000	0	0
BAD	-0.061	0.023	-10000	0	-0.12	9	9
SMPD1	0.012	0.019	-10000	0	-0.16	3	3
RB1	-0.061	0.023	-10000	0	-0.12	9	9
FADD/Caspase 8	0.023	0.021	-10000	0	-10000	0	0
MAP2K4	-0.057	0.021	-10000	0	-0.12	9	9
NSMAF	0.01	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.056	0.022	-10000	0	-0.12	9	9
EGF	-0.4	0.14	-10000	0	-0.44	261	261
mol:ceramide	-0.067	0.024	-10000	0	-0.13	9	9
MADD	0.01	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.009	0.002	-10000	0	-10000	0	0
ASAH1	0.01	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.061	0.022	-10000	0	-0.12	9	9
cell proliferation	-0.047	0.033	-10000	0	-0.22	6	6
BID	-0.002	0.017	-10000	0	-10000	0	0
MAP3K1	-0.061	0.023	-10000	0	-0.12	9	9
EIF2A	-0.053	0.02	-10000	0	-10000	0	0
TRADD	0.01	0	-10000	0	-10000	0	0
CRADD	0.01	0	-10000	0	-10000	0	0
MAPK3	-0.05	0.02	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.05	0.02	-10000	0	-10000	0	0
Cathepsin D/ceramide	-0.06	0.024	-10000	0	-0.12	9	9
FADD	0.014	0.02	-10000	0	-10000	0	0
KSR1	-0.061	0.023	-10000	0	-0.12	9	9
MAPK8	-0.055	0.036	-10000	0	-0.28	5	5
PRKRA	-0.061	0.023	-10000	0	-0.12	9	9
PDGFA	0.009	0.002	-10000	0	-10000	0	0
TRAF2	0.01	0	-10000	0	-10000	0	0
IGF1	0	0.064	-10000	0	-0.44	6	6
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.067	0.024	-10000	0	-0.13	9	9
CTSD	0.01	0.001	-10000	0	-10000	0	0
regulation of nitric oxide biosynthetic process	0.015	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.049	0.035	-10000	0	-0.23	6	6
PRKCD	0.01	0	-10000	0	-10000	0	0
PRKCZ	0.01	0	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.009	0.002	-10000	0	-10000	0	0
RelA/NF kappa B1	0.015	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.01	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.014	0.021	-10000	0	-0.18	3	3
TNFR1A/BAG4/TNF-alpha	0.016	0.028	-10000	0	-0.26	3	3
mol:Sphingosine-1-phosphate	0.009	0.002	-10000	0	-10000	0	0
MAP2K1	-0.053	0.021	-10000	0	-10000	0	0
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.01	0	-10000	0	-10000	0	0
CYCS	-0.04	0.015	-10000	0	-10000	0	0
TNFRSF1A	0.01	0	-10000	0	-10000	0	0
NFKB1	0.01	0	-10000	0	-10000	0	0
TNFR1A/BAG4	0.015	0	-10000	0	-10000	0	0
EIF2AK2	-0.057	0.021	-10000	0	-0.12	9	9
TNF-alpha/TNFR1A/FAN	0.016	0.028	-10000	0	-0.26	3	3
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.018	0.014	-10000	0	-10000	0	0
MAP2K2	-0.053	0.021	-10000	0	-10000	0	0
SMPD3	0.015	0.02	-10000	0	-0.16	3	3
TNF	0.005	0.046	-10000	0	-0.44	3	3
PKC zeta/PAR4	0.015	0	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	0.18	0.061	0.2	261	-10000	0	261
NF kappa B1/RelA/I kappa B alpha	0.029	0	-10000	0	-10000	0	0
AIFM1	-0.04	0.015	-10000	0	-10000	0	0
BCL2	0.01	0	-10000	0	-10000	0	0

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.014	0.001	-9999	-10000	0	0
VLDLR	0.01	0	-9999	-10000	0	0
CRKL	0.01	0	-9999	-10000	0	0
LRPAP1	0.01	0	-9999	-10000	0	0
FYN	0.01	0	-9999	-10000	0	0
ITGA3	0.009	0.002	-9999	-10000	0	0
RELN/VLDLR/Fyn	-0.001	0.061	-9999	-0.26	15	15
MAPK8IP1/MKK7/MAP3K11/JNK1	0.025	0.032	-9999	-0.22	5	5
AKT1	-0.003	0.047	-9999	-0.2	15	15
MAP2K7	0.01	0	-9999	-10000	0	0
RAPGEF1	0.01	0	-9999	-10000	0	0
DAB1	0.004	0.005	-9999	-10000	0	0
RELN/LRP8/DAB1	-0.003	0.052	-9999	-0.22	15	15
LRPAP1/LRP8	0.014	0.002	-9999	-10000	0	0
RELN/LRP8/DAB1/Fyn	0.001	0.049	-9999	-0.2	15	15
DAB1/alpha3/beta1 Integrin	0.001	0.045	-9999	-0.2	12	12
long-term memory	-0.042	0.095	-9999	-0.22	49	49
DAB1/LIS1	0.004	0.048	-9999	-0.2	12	12
DAB1/CRLK/C3G	0.002	0.045	-9999	-0.2	12	12
PIK3CA	0.01	0	-9999	-10000	0	0
DAB1/NCK2	0.005	0.048	-9999	-0.21	12	12
ARHGEF2	0.01	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.095	0.19	-9999	-0.44	67	67
CDK5R1	0.01	0.001	-9999	-10000	0	0
RELN	-0.017	0.099	-9999	-0.44	15	15
PIK3R1	0.01	0	-9999	-10000	0	0
RELN/LRP8/Fyn	-0.001	0.059	-9999	-0.25	15	15
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.043	0.1	-9999	-0.2	79	79
MAPK8	0.002	0.059	-9999	-0.44	5	5
RELN/VLDLR/DAB1	-0.003	0.054	-9999	-0.23	15	15
ITGB1	0.01	0	-9999	-10000	0	0
MAP1B	-0.003	0.05	-9999	-0.21	15	15
RELN/LRP8	-0.001	0.059	-9999	-0.25	15	15
GRIN2B/RELN/LRP8/DAB1/Fyn	0.002	0.05	-9999	-0.2	15	15
PI3K	0.015	0	-9999	-10000	0	0
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	0.014	0.003	-9999	-10000	0	0
RAP1A	0.029	0.057	-9999	-0.19	12	12
PAFAH1B1	0.01	0	-9999	-10000	0	0
MAPK8IP1	0.01	0	-9999	-10000	0	0
CRLK/C3G	0.015	0	-9999	-10000	0	0
GRIN2B	0.005	0.005	-9999	-10000	0	0
NCK2	0.01	0	-9999	-10000	0	0
neuron differentiation	0.015	0.046	-9999	-10000	0	0
neuron adhesion	0.034	0.057	-9999	-10000	0	0
LRP8	0.01	0.001	-9999	-10000	0	0
GSK3B	-0.003	0.044	-9999	-0.19	14	14
RELN/VLDLR/DAB1/Fyn	0	0.051	-9999	-0.21	15	15
MAP3K11	0.01	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.004	0.05	-9999	-0.22	15	15
CDK5	0.01	0	-9999	-10000	0	0
MAPT	-0.012	0.073	-9999	-0.4	10	10
neuron migration	0.019	0.067	-9999	-0.25	15	15
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	0.015	0.047	-9999	-10000	0	0
RELN/VLDLR	0.003	0.054	-9999	-0.22	15	15

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.01	0.003	-9999	-10000	0	0
VDR	0.002	0.059	-9999	-0.44	5	5
FAM120B	0.01	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.027	0.035	-9999	-0.25	3	3
RXRs/LXRs/DNA/Oxysterols	0.023	0.042	-9999	-0.39	3	3
MED1	0.01	0	-9999	-10000	0	0
mol:9cRA	0.003	0.007	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	0.008	0.044	-9999	-0.21	11	11
RXRs/NUR77	-0.079	0.13	-9999	-0.23	122	122
RXRs/PPAR	0.019	0.01	-9999	-10000	0	0
NCOR2	0.01	0	-9999	-10000	0	0
VDR/VDR/Vit D3	0.002	0.042	-9999	-0.31	5	5
RARs/VDR/DNA/Vit D3	0.019	0.031	-9999	-0.22	5	5
RARA	0.01	0	-9999	-10000	0	0
NCOA1	0.01	0	-9999	-10000	0	0
VDR/VDR/DNA	0.002	0.058	-9999	-0.44	5	5
RARs/RARs/DNA/9cRA	0.019	0.004	-9999	-10000	0	0
RARG	0.01	0.001	-9999	-10000	0	0
RPS6KB1	0.008	0.006	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	0.008	0.044	-9999	-0.21	11	11
THRA	0.01	0	-9999	-10000	0	0
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	0.002	0.042	-9999	-0.31	5	5
RXRs/PPAR/9cRA/PGJ2/DNA	0.026	0.024	-9999	-10000	0	0
NR1H4	0.004	0.052	-9999	-0.44	4	4
RXRs/LXRs/DNA	0.04	0.029	-9999	-10000	0	0
NR1H2	0.013	0.007	-9999	-10000	0	0
NR1H3	0.013	0.007	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.022	0.036	-9999	-0.23	5	5
NR4A1	-0.18	0.22	-9999	-0.44	122	122
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	0.014	0.029	-9999	-0.2	4	4
RXRG	0.006	0.008	-9999	-10000	0	0
RXR alpha/CCPG	0.017	0.005	-9999	-10000	0	0
RXRA	0.013	0.007	-9999	-10000	0	0
RXRB	0.013	0.007	-9999	-10000	0	0
THRB	-0.007	0.086	-9999	-0.44	11	11
PPARG	0.01	0.001	-9999	-10000	0	0
PPARD	0.01	0	-9999	-10000	0	0
TNF	0.017	0.1	-9999	-0.96	3	3
mol:Oxysterols	0.003	0.006	-9999	-10000	0	0
cholesterol transport	0.025	0.044	-9999	-0.38	3	3
PPARA	0.01	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	0.01	0	-9999	-10000	0	0
RXRs/NUR77/BCL2	-0.083	0.12	-9999	-0.22	122	122
SREBF1	0.03	0.046	-9999	-10000	0	0
RXRs/RXRs/DNA/9cRA	0.026	0.024	-9999	-10000	0	0
ABCA1	0.031	0.046	-9999	-10000	0	0
RARs/THRs	0.02	0.047	-9999	-0.22	11	11
RXRs/FXR	0.025	0.033	-9999	-0.22	4	4
BCL2	0.01	0	-9999	-10000	0	0

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.088	0.1	-9999	-0.46	1	1
RAD9A	0.01	0.001	-9999	-10000	0	0
AP1	-0.032	0.12	-9999	-0.31	44	44
IFNAR2	0.012	0.004	-9999	-10000	0	0
AKT1	0.001	0.044	-9999	-0.17	17	17
ER alpha/Oestrogen	-0.01	0.075	-9999	-0.31	17	17
NFX1/SIN3/HDAC complex	0.022	0.007	-9999	-10000	0	0
EGF	-0.39	0.14	-9999	-0.44	261	261
SMG5	0.01	0	-9999	-10000	0	0
SMG6	0.01	0	-9999	-10000	0	0
SP3/HDAC2	0.018	0.007	-9999	-10000	0	0
TERT/c-Abl	-0.086	0.084	-9999	-0.43	1	1
SAP18	0.01	0.001	-9999	-10000	0	0
MRN complex	0.019	0.016	-9999	-0.26	1	1
WT1	-0.24	0.22	-9999	-0.44	161	161
WRN	0.01	0	-9999	-10000	0	0
SP1	0.013	0.006	-9999	-10000	0	0
SP3	0.011	0.002	-9999	-10000	0	0
TERF2IP	0.01	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.081	0.075	-9999	-0.4	1	1
Mad/Max	0.017	0.005	-9999	-10000	0	0
TERT	-0.09	0.1	-9999	-0.47	1	1
CCND1	-0.079	0.11	-9999	-1.1	1	1
MAX	0.011	0.002	-9999	-10000	0	0
RBBP7	0.01	0.001	-9999	-10000	0	0
RBBP4	0.01	0.001	-9999	-10000	0	0
TERF2	0.009	0	-9999	-10000	0	0
PTGES3	0.01	0	-9999	-10000	0	0
SIN3A	0.01	0.001	-9999	-10000	0	0
Telomerase/911	0.001	0.021	-9999	-10000	0	0
CDKN1B	0.014	0.005	-9999	-10000	0	0
RAD1	0.01	0	-9999	-10000	0	0
XRCC5	0.01	0	-9999	-10000	0	0
XRCC6	0.01	0	-9999	-10000	0	0
SAP30	0.01	0.001	-9999	-10000	0	0
TRF2/PARP2	0.014	0	-9999	-10000	0	0
UBE3A	0.011	0.002	-9999	-10000	0	0
JUN	0.011	0.002	-9999	-10000	0	0
E6	0.001	0.002	-9999	-10000	0	0
HPV-16 E6/E6AP	0.009	0.004	-9999	-10000	0	0
FOS	-0.058	0.16	-9999	-0.44	44	44
IFN-gamma/IRF1	0.018	0.007	-9999	-10000	0	0
PARP2	0.01	0	-9999	-10000	0	0
BLM	0.009	0.002	-9999	-10000	0	0
Telomerase	-0.005	0.022	-9999	-10000	0	0
IRF1	0.013	0.002	-9999	-10000	0	0
ESR1	-0.016	0.11	-9999	-0.44	17	17
KU/TER	0.015	0	-9999	-10000	0	0
ATM/TRF2	0.015	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.025	0.007	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.026	0.007	-9999	-10000	0	0
HDAC1	0.01	0.001	-9999	-10000	0	0
HDAC2	0.012	0.005	-9999	-10000	0	0
ATM	0.003	0	-9999	-10000	0	0
SMAD3	0.007	0.004	-9999	-10000	0	0
ABL1	0.01	0	-9999	-10000	0	0
MXD1	0.011	0.002	-9999	-10000	0	0
MRE11A	0.01	0	-9999	-10000	0	0
HUS1	0.01	0	-9999	-10000	0	0
RPS6KB1	0.01	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.053	0.091	-9999	-0.4	1	1
NR2F2	0.007	0.006	-9999	-10000	0	0
MAPK3	0.008	0.004	-9999	-10000	0	0
MAPK1	0.008	0.004	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.009	0.001	-9999	-10000	0	0
NFKB1	0.01	0	-9999	-10000	0	0
HNRNPC	0.01	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.003	0	-9999	-10000	0	0
NBN	0.01	0	-9999	-10000	0	0
EGFR	0.01	0.001	-9999	-10000	0	0
mol:Oestrogen	0.001	0.001	-9999	-10000	0	0
EGF/EGFR	-0.28	0.098	-9999	-0.31	261	261
MYC	0.011	0.003	-9999	-10000	0	0
IL2	0.006	0.008	-9999	-10000	0	0
KU	0.015	0	-9999	-10000	0	0
RAD50	0.008	0.026	-9999	-0.44	1	1
HSP90AA1	0.01	0	-9999	-10000	0	0
TGFB1	0.009	0.001	-9999	-10000	0	0
TRF2/BLM	0.013	0.004	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.077	0.098	-9999	-0.43	1	1
SP1/HDAC2	0.02	0.012	-9999	-10000	0	0
PINX1	0.01	0	-9999	-10000	0	0
Telomerase/EST1A	-0.081	0.075	-9999	-0.4	1	1
Smad3/Myc	0.013	0.003	-9999	-10000	0	0
911 complex	0.02	0.001	-9999	-10000	0	0
IFNG	0.008	0.005	-9999	-10000	0	0
Telomerase/PinX1	-0.081	0.075	-9999	-0.4	1	1
Telomerase/AKT1/mTOR/p70S6K	-0.006	0.036	-9999	-10000	0	0
SIN3B	0.01	0.001	-9999	-10000	0	0
YWHAE	0.01	0	-9999	-10000	0	0
Telomerase/EST1B	-0.081	0.075	-9999	-0.4	1	1
response to DNA damage stimulus	0.002	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0.027	0.014	-9999	-0.21	1	1
TRF2/WRN	0.014	0	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.081	0.075	-9999	-0.4	1	1
E2F1	0.008	0.006	-9999	-10000	0	0
ZNFX1	0.01	0.001	-9999	-10000	0	0
PIF1	0.009	0.003	-9999	-10000	0	0
NCL	0.01	0	-9999	-10000	0	0
DKC1	0.01	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.01	0	-9999	-10000	0	0
GNAT1/GTP	0.002	0.003	-9999	-10000	0	0
Metarhodopsin II/Arrestin	0.003	0.004	-9999	-10000	0	0
PDE6G/GNAT1/GTP	0.002	0.038	-9999	-0.26	6	6
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.002	0.004	-9999	-10000	0	0
GRK1	0.002	0.004	-9999	-10000	0	0
CNG Channel	-0.048	0.098	-9999	-0.2	79	79
mol:Na +	-0.039	0.088	-9999	-0.2	62	62
mol:ADP	0.002	0.004	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.015	0.035	-9999	-0.24	5	5
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.038	0.091	-9999	-0.2	62	62
CNGB1	0.007	0.005	-9999	-10000	0	0
RDH5	0.006	0.037	-9999	-0.44	2	2
SAG	0	0.002	-9999	-10000	0	0
mol:Ca2+	-0.029	0.093	-9999	-0.19	62	62
Na + (4 Units)	-0.038	0.083	-9999	-0.19	62	62
RGS9	0.003	0.052	-9999	-0.44	4	4
GNB1/GNGT1	0.01	0.005	-9999	-10000	0	0
GNAT1/GDP	0.014	0.029	-9999	-0.2	5	5
GUCY2D	0.007	0.004	-9999	-10000	0	0
GNGT1	0.006	0.005	-9999	-10000	0	0
GUCY2F	0.001	0.003	-9999	-10000	0	0
GNB5	0.01	0	-9999	-10000	0	0
mol:GMP (4 units)	0.005	0.038	-9999	-0.22	8	8
mol:11-cis-retinal	0.006	0.037	-9999	-0.44	2	2
mol:cGMP	0.012	0.007	-9999	-10000	0	0
GNB1	0.01	0	-9999	-10000	0	0
Rhodopsin	0.008	0.027	-9999	-0.31	2	2
SLC24A1	0.01	0	-9999	-10000	0	0
CNGA1	-0.11	0.2	-9999	-0.44	78	78
Metarhodopsin II	0.004	0.004	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	0.014	0.008	-9999	-10000	0	0
RGS9BP	0.008	0.026	-9999	-0.44	1	1
Metarhodopsin II/Transducin	0.006	0.003	-9999	-10000	0	0
GCAP Family/Ca ++	0.012	0.005	-9999	-10000	0	0
PDE6A/B	0.01	0.027	-9999	-0.31	2	2
mol:Pi	0.014	0.034	-9999	-0.24	5	5
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	0.01	0.006	-9999	-10000	0	0
PDE6B	0.007	0.037	-9999	-0.44	2	2
PDE6A	0.007	0.004	-9999	-10000	0	0
PDE6G	0	0.064	-9999	-0.44	6	6
RHO	0.005	0.005	-9999	-10000	0	0
PDE6	0.016	0.05	-9999	-0.23	10	10
GUCA1A	0.004	0.005	-9999	-10000	0	0
GC2/GCAP Family	0.012	0.005	-9999	-10000	0	0
GUCA1C	0.005	0.005	-9999	-10000	0	0
GUCA1B	0.01	0.001	-9999	-10000	0	0

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.01	0	-9999	-10000	0	0
SPHK1	0.005	0.005	-9999	-10000	0	0
GNAI2	0.01	0	-9999	-10000	0	0
mol:S1P	0.005	0.005	-9999	-10000	0	0
GNAO1	-0.029	0.13	-9999	-0.44	25	25
mol:Sphinganine-1-P	0.005	0.005	-9999	-10000	0	0
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.038	0.013	-9999	-10000	0	0
GNAI3	0.01	0	-9999	-10000	0	0
G12/G13	0.015	0.001	-9999	-10000	0	0
S1PR3	-0.026	0.12	-9999	-0.44	23	23
S1PR2	0.01	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	0.003	0.003	-9999	-10000	0	0
S1PR5	0.005	0.046	-9999	-0.44	3	3
S1PR4	0.01	0.001	-9999	-10000	0	0
GNAI1	0.007	0.037	-9999	-0.44	2	2
S1P/S1P5/G12	0.03	0.028	-9999	-0.2	3	3
S1P/S1P3/Gq	-0.046	0.13	-9999	-0.26	66	66
S1P/S1P4/Gi	0.006	0.065	-9999	-0.2	27	27
GNAQ	0.01	0	-9999	-10000	0	0
GNAZ	0.01	0	-9999	-10000	0	0
GNA14	-0.085	0.18	-9999	-0.44	61	61
GNA15	0.009	0.002	-9999	-10000	0	0
GNA12	0.01	0	-9999	-10000	0	0
GNA13	0.01	0.001	-9999	-10000	0	0
GNA11	-0.001	0.069	-9999	-0.44	7	7
ABCC1	0.01	0	-9999	-10000	0	0

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.01	0	-10000	0	-10000	0	0
LAT2	0.002	0.034	-10000	0	-0.2	2	2
AP1	-0.006	0.088	-10000	0	-0.34	9	9
mol:PIP3	0.063	0.082	0.21	34	-0.24	8	42
IKBKB	0.048	0.057	0.16	32	-0.17	2	34
AKT1	0.046	0.059	0.15	21	-0.18	8	29
IKBKG	0.048	0.057	0.16	32	-0.17	2	34
MS4A2	0.005	0.026	-10000	0	-0.43	1	1
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.01	0.001	-10000	0	-10000	0	0
MAP3K1	0.048	0.056	0.17	1	-0.24	2	3
mol:Ca2+	0.057	0.071	0.18	40	-0.19	8	48
LYN	0.013	0.003	-10000	0	-10000	0	0
CBLB	0.002	0.033	-10000	0	-0.22	1	1
SHC1	0.01	0	-10000	0	-10000	0	0
RasGAP/p62DOK	0.018	0.015	-10000	0	-0.23	1	1
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	0.009	0.002	-10000	0	-10000	0	0
PLD2	0.043	0.062	0.15	27	-0.21	9	36
PTPN13	0.033	0.042	-10000	0	-10000	0	0
PTPN11	0.011	0.005	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	0.046	0.051	0.16	3	-0.18	1	4
SYK	0.011	0.027	-10000	0	-0.45	1	1
GRB2	0.01	0	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.007	0.04	-10000	0	-0.24	8	8
LAT	0.002	0.031	-10000	0	-0.2	2	2
PAK2	0.049	0.06	0.18	1	-0.26	2	3
NFATC2	-0.031	0.11	-10000	0	-0.42	22	22
HRAS	0.049	0.062	0.17	3	-0.28	2	5
GAB2	0.01	0	-10000	0	-10000	0	0
PLA2G1B	0.006	0.009	-10000	0	-10000	0	0
Fc epsilon R1	0.002	0.049	-10000	0	-0.27	9	9
Antigen/IgE/Fc epsilon R1	0.002	0.045	-10000	0	-0.24	9	9
mol:GDP	0.033	0.058	-10000	0	-0.29	2	2
JUN	0.01	0	-10000	0	-10000	0	0
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.01	0.001	-10000	0	-10000	0	0
FOS	-0.058	0.16	-10000	0	-0.44	44	44
Antigen/IgE/Fc epsilon R1/LYN/SYK	0.002	0.035	-10000	0	-0.18	8	8
CHUK	0.048	0.057	0.15	38	-0.17	2	40
KLRG1	0.002	0.033	-10000	0	-0.17	8	8
VAV1	0.001	0.038	-10000	0	-0.3	2	2
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	0.002	0.033	-10000	0	-0.2	2	2
negative regulation of mast cell degranulation	0.004	0.032	-10000	0	-0.17	2	2
BTK	0.004	0.034	-10000	0	-0.22	2	2
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	0.002	0.05	-10000	0	-0.25	9	9
GAB2/PI3K/SHP2	-0.006	0.033	-10000	0	-0.2	8	8
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	0.011	0.042	-10000	0	-0.19	9	9
RAF1	0.002	0.011	-10000	0	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	0.006	0.048	-10000	0	-0.24	9	9
FCER1G	0.006	0.005	-10000	0	-10000	0	0
FCER1A	0	0.076	-10000	0	-0.45	8	8
Antigen/IgE/Fc epsilon R1/Fyn	0.005	0.042	-10000	0	-0.22	9	9
MAPK3	0.005	0.009	-10000	0	-10000	0	0
MAPK1	0.005	0.009	-10000	0	-10000	0	0
NFKB1	0.01	0	-10000	0	-10000	0	0
MAPK8	0.021	0.074	-10000	0	-0.52	5	5
DUSP1	0.008	0.026	-10000	0	-0.44	1	1
NF-kappa-B/RelA	0.008	0.02	-10000	0	-0.12	1	1
actin cytoskeleton reorganization	0.033	0.044	-10000	0	-10000	0	0
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	0.016	0.041	-10000	0	-0.28	2	2
FER	0.002	0.033	-10000	0	-0.2	2	2
RELA	0.01	0	-10000	0	-10000	0	0
ITK	0.003	0.01	-10000	0	-10000	0	0
SOS1	0.01	0	-10000	0	-10000	0	0
PLCG1	0.051	0.066	0.17	13	-0.3	2	15
cytokine secretion	0.002	0.013	-10000	0	-10000	0	0
SPHK1	0	0.029	-10000	0	-0.2	2	2
PTK2	0.033	0.044	-10000	0	-10000	0	0
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.008	0.042	-10000	0	-0.24	8	8
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	0.061	0.078	0.22	21	-0.23	8	29
MAP2K2	0.003	0.01	-10000	0	-10000	0	0
MAP2K1	0.003	0.01	-10000	0	-10000	0	0
MAP2K7	0.01	0	-10000	0	-10000	0	0
KLRG1/SHP2	0.003	0.033	-10000	0	-0.18	1	1
MAP2K4	0.018	0.005	-10000	0	-10000	0	0
Fc epsilon R1/FcgammaRIIB	0.004	0.051	-10000	0	-0.26	9	9
mol:Choline	0.042	0.062	0.14	27	-0.2	9	36
SHC/Grb2/SOS1	0.018	0.037	-10000	0	-0.21	1	1
FYN	0.01	0	-10000	0	-10000	0	0
DOK1	0.01	0.001	-10000	0	-10000	0	0
PXN	0.033	0.042	-10000	0	-10000	0	0
HCLS1	0.002	0.033	-10000	0	-0.2	2	2
PRKCB	0.054	0.068	0.18	32	-0.19	8	40
FCGR2B	0.005	0.027	-10000	0	-0.44	1	1
IGHE	0.003	0.004	-10000	0	-10000	0	0
KLRG1/SHIP	0.004	0.033	-10000	0	-0.17	2	2
LCP2	0.01	0.002	-10000	0	-10000	0	0
PLA2G4A	-0.003	0.051	-10000	0	-0.25	7	7
RASA1	0.01	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.042	0.062	0.14	27	-0.2	9	36
IKK complex	0.046	0.05	0.14	32	-0.15	1	33
WIPF1	0.01	0.001	-10000	0	-10000	0	0

×

IL23-mediated signaling events

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
CCL2	0.083	0.28	0.59	3	-0.98	7	10
IL23A	0.086	0.28	0.64	3	-0.85	10	13
NF kappa B1 p50/RelA/I kappa B alpha	-0.011	0.19	-10000	0	-0.72	8	8
positive regulation of T cell mediated cytotoxicity	0.091	0.27	0.62	6	-0.8	8	14
ITGA3	0.09	0.26	0.64	3	-0.8	6	9
IL17F	0.077	0.2	0.46	5	-0.56	6	11
IL12B	0.029	0.04	0.17	1	-10000	0	1
STAT1 (dimer)	0.078	0.25	0.54	4	-0.77	8	12
CD4	0.092	0.26	0.59	5	-0.77	6	11
IL23	0.076	0.27	0.61	2	-0.83	10	12
IL23R	0.055	0.092	0.42	2	-10000	0	2
IL1B	0.081	0.3	0.63	3	-1.1	8	11
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	0.089	0.25	0.62	3	-0.77	6	9
TYK2	0.023	0.027	-10000	0	-10000	0	0
STAT4	0.009	0.003	-10000	0	-10000	0	0
STAT3	0.01	0.001	-10000	0	-10000	0	0
IL18RAP	0.009	0.004	-10000	0	-10000	0	0
IL12RB1	0.02	0.026	-10000	0	-10000	0	0
PIK3CA	0.01	0.001	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	0.025	0.031	-10000	0	-10000	0	0
IL23R/JAK2	0.073	0.11	0.42	1	-10000	0	1
positive regulation of chronic inflammatory response	0.091	0.27	0.62	6	-0.8	8	14
natural killer cell activation	-0.004	0.008	-10000	0	-0.033	3	3
JAK2	0.033	0.04	0.15	7	-10000	0	7
PIK3R1	0.01	0.001	-10000	0	-10000	0	0
NFKB1	0.012	0.004	-10000	0	-10000	0	0
RELA	0.012	0.004	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	0.077	0.26	0.6	2	-0.8	10	12
ALOX12B	0.091	0.25	0.59	3	-0.77	6	9
CXCL1	0.087	0.31	0.61	7	-0.93	12	19
T cell proliferation	0.091	0.27	0.62	6	-0.8	8	14
NFKBIA	0.012	0.004	-10000	0	-10000	0	0
IL17A	0.085	0.18	0.43	7	-0.44	6	13
PI3K	0.02	0.21	-10000	0	-0.75	8	8
IFNG	0.012	0.024	0.098	10	-10000	0	10
STAT3 (dimer)	-0.013	0.19	-10000	0	-0.72	8	8
IL18R1	0.009	0.027	-10000	0	-0.44	1	1
IL23/IL23R/JAK2/TYK2/SOCS3	0.086	0.19	0.47	8	-0.57	3	11
IL18/IL18R	0.017	0.023	-10000	0	-0.26	1	1
macrophage activation	-0.003	0.012	-10000	0	-0.04	10	10
TNF	0.085	0.28	0.62	4	-0.94	8	12
STAT3/STAT4	0.017	0.21	-10000	0	-0.74	8	8
STAT4 (dimer)	0.066	0.25	0.55	3	-0.77	8	11
IL18	0.01	0.003	-10000	0	-10000	0	0
IL19	0.087	0.25	0.59	3	-0.77	6	9
STAT5A (dimer)	0.08	0.26	0.55	3	-0.77	8	11
STAT1	0.01	0.001	-10000	0	-10000	0	0
SOCS3	0.008	0.026	-10000	0	-0.44	1	1
CXCL9	0.089	0.26	0.6	4	-0.81	7	11
MPO	0.093	0.25	0.6	4	-0.76	6	10
positive regulation of humoral immune response	0.091	0.27	0.62	6	-0.8	8	14
IL23/IL23R/JAK2/TYK2	0.09	0.28	0.63	5	-0.82	8	13
IL6	0.016	0.41	0.62	4	-1	32	36
STAT5A	0.01	0	-10000	0	-10000	0	0
IL2	0.003	0.01	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	-0.004	0.008	-10000	0	-0.033	3	3
CD3E	0.093	0.27	0.61	6	-0.85	6	12
keratinocyte proliferation	0.091	0.27	0.62	6	-0.8	8	14
NOS2	0.036	0.37	0.59	3	-0.98	26	29

×

Regulation of Androgen receptor activity

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.009	0.001	-9999	-10000	0	0
SMARCC1	0.003	0.009	-9999	-10000	0	0
REL	0.001	0.059	-9999	-0.44	5	5
HDAC7	-0.1	0.098	-9999	-0.4	5	5
JUN	0.01	0.001	-9999	-10000	0	0
EP300	0.01	0	-9999	-10000	0	0
KAT2B	0.01	0	-9999	-10000	0	0
KAT5	0.01	0	-9999	-10000	0	0
MAPK14	-0.011	0.017	-9999	-10000	0	0
FOXO1	0.01	0	-9999	-10000	0	0
T-DHT/AR	-0.1	0.11	-9999	-0.38	6	6
MAP2K6	-0.005	0.012	-9999	-10000	0	0
BRM/BAF57	0.016	0.004	-9999	-10000	0	0
MAP2K4	-0.005	0.012	-9999	-10000	0	0
SMARCA2	0.01	0.002	-9999	-10000	0	0
PDE9A	-0.13	0.12	-9999	-0.39	2	2
NCOA2	-0.03	0.13	-9999	-0.44	26	26
CEBPA	0.007	0.026	-9999	-0.44	1	1
EHMT2	0.01	0.001	-9999	-10000	0	0
cell proliferation	-0.15	0.14	-9999	-0.4	46	46
NR0B1	0.004	0.005	-9999	-10000	0	0
EGR1	-0.025	0.12	-9999	-0.44	23	23
RXRs/9cRA	0.016	0.005	-9999	-10000	0	0
AR/RACK1/Src	-0.03	0.06	-9999	-0.34	4	4
AR/GR	-0.021	0.058	-9999	-0.24	14	14
GNB2L1	0.01	0.001	-9999	-10000	0	0
PKN1	0.01	0	-9999	-10000	0	0
RCHY1	0.01	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0.001	-9999	-10000	0	0
MAPK8	-0.016	0.045	-9999	-0.33	5	5
T-DHT/AR/TIF2/CARM1	-0.05	0.097	-9999	-0.31	24	24
SRC	-0.03	0.043	-9999	-0.25	5	5
NR3C1	0.01	0	-9999	-10000	0	0
KLK3	-0.013	0.1	-9999	-10000	0	0
APPBP2	-0.006	0.012	-9999	-10000	0	0
TRIM24	0.011	0.002	-9999	-10000	0	0
T-DHT/AR/TIP60	-0.041	0.057	-9999	-0.33	5	5
TMPRSS2	-0.66	0.48	-9999	-1	186	186
RXRG	0.003	0.005	-9999	-10000	0	0
mol:9cRA	0	0	-9999	-10000	0	0
RXRA	0.01	0	-9999	-10000	0	0
RXRB	0.01	0	-9999	-10000	0	0
CARM1	0.01	0.001	-9999	-10000	0	0
NR2C2	0.005	0.046	-9999	-0.44	3	3
KLK2	-0.039	0.075	-9999	-0.44	4	4
AR	-0.027	0.063	-9999	-0.27	14	14
SENP1	0.01	0	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
MDM2	0.008	0.005	-9999	-10000	0	0
SRY	-0.001	0.004	-9999	-10000	0	0
GATA2	-0.083	0.18	-9999	-0.44	60	60
MYST2	0.01	0	-9999	-10000	0	0
HOXB13	0.006	0.006	-9999	-10000	0	0
T-DHT/AR/RACK1/Src	-0.035	0.057	-9999	-0.35	4	4
positive regulation of transcription	-0.083	0.18	-9999	-0.44	60	60
DNAJA1	-0.006	0.012	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.012	0.001	-9999	-10000	0	0
NCOA1	0.016	0.003	-9999	-10000	0	0
SPDEF	0.009	0.005	-9999	-10000	0	0
T-DHT/AR/TIF2	-0.029	0.075	-9999	-0.26	19	19
T-DHT/AR/Hsp90	-0.041	0.057	-9999	-0.33	5	5
GSK3B	0.007	0.003	-9999	-10000	0	0
NR2C1	0.01	0.001	-9999	-10000	0	0
mol:T-DHT	-0.035	0.046	-9999	-0.28	5	5
SIRT1	0.01	0	-9999	-10000	0	0
ZMIZ2	0.008	0.005	-9999	-10000	0	0
POU2F1	-0.051	0.049	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.035	0.054	-9999	-0.3	5	5
CREBBP	0.01	0	-9999	-10000	0	0
SMARCE1	0.01	0.002	-9999	-10000	0	0

×

Caspase cascade in apoptosis

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
TOP1	0.017	0.017	-10000	0	-10000	0	0
ACTA1	0.01	0.02	-10000	0	-10000	0	0
NUMA1	0.017	0.017	-10000	0	-10000	0	0
SPTAN1	0.01	0.02	-10000	0	-10000	0	0
LIMK1	0.011	0.022	-10000	0	-10000	0	0
BIRC3	0.009	0.002	-10000	0	-10000	0	0
BIRC2	0.01	0	-10000	0	-10000	0	0
BAX	0.01	0.001	-10000	0	-10000	0	0
CASP10	0.008	0.002	-10000	0	-10000	0	0
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.01	0	-10000	0	-10000	0	0
PTK2	0.017	0.017	-10000	0	-10000	0	0
DIABLO	0.01	0	-10000	0	-10000	0	0
apoptotic nuclear changes	0.01	0.02	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.01	0	-10000	0	-10000	0	0
GSN	0.01	0.02	-10000	0	-10000	0	0
MADD	0.01	0	-10000	0	-10000	0	0
TFAP2A	-0.37	0.21	-10000	0	-0.48	229	229
BID	0.007	0.002	-10000	0	-10000	0	0
MAP3K1	0.009	0.01	-10000	0	-10000	0	0
TRADD	0.01	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.014	0	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	0.01	0.022	-10000	0	-10000	0	0
CASP9	0.01	0	-10000	0	-10000	0	0
DNA repair	-0.004	0.012	-10000	0	-10000	0	0
neuron apoptosis	0.015	0.004	-10000	0	-10000	0	0
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.015	0.019	-10000	0	-10000	0	0
APAF1	0.01	0	-10000	0	-10000	0	0
CASP6	0.02	0.014	-10000	0	-10000	0	0
TRAF2	0.01	0	-10000	0	-10000	0	0
ICAD/CAD	0.011	0.019	-10000	0	-10000	0	0
CASP7	-0.01	0.021	-10000	0	-10000	0	0
KRT18	0.013	0.005	-10000	0	-10000	0	0
apoptosis	0.014	0.021	0.17	1	-10000	0	1
DFFA	0.01	0.02	-10000	0	-10000	0	0
DFFB	0.01	0.02	-10000	0	-10000	0	0
PARP1	0.004	0.012	-10000	0	-10000	0	0
actin filament polymerization	-0.012	0.021	-10000	0	-10000	0	0
TNF	0.005	0.046	-10000	0	-0.44	3	3
CYCS	0.013	0.016	0.1	2	-10000	0	2
SATB1	0.02	0.018	-10000	0	-10000	0	0
SLK	0.01	0.02	-10000	0	-10000	0	0
p15 BID/BAX	0.017	0.013	-10000	0	-10000	0	0
CASP2	0.018	0.021	-10000	0	-10000	0	0
JNK cascade	-0.009	0.01	-10000	0	-10000	0	0
CASP3	0.009	0.021	-10000	0	-10000	0	0
LMNB2	0.025	0.016	-10000	0	-10000	0	0
RIPK1	0.01	0	-10000	0	-10000	0	0
CASP4	0.01	0	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	0.024	0.006	-10000	0	-10000	0	0
negative regulation of DNA binding	-0.37	0.21	-10000	0	-0.47	229	229
stress fiber formation	0.01	0.02	-10000	0	-10000	0	0
GZMB	0.008	0.002	-10000	0	-10000	0	0
CASP1	0.008	0.001	-10000	0	-10000	0	0
LMNB1	0.025	0.016	-10000	0	-10000	0	0
APP	0.015	0.004	-10000	0	-10000	0	0
TNFRSF1A	0.01	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.005	0	-10000	0	-10000	0	0
VIM	0.013	0.021	0.17	1	-10000	0	1
LMNA	0.025	0.016	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.018	0.022	-10000	0	-0.18	3	3
LRDD	0.01	0.001	-10000	0	-10000	0	0
SREBF1	0.01	0.02	-10000	0	-10000	0	0
APAF-1/Caspase 9	0.005	0.002	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0.017	0.017	-10000	0	-10000	0	0
CFL2	0.012	0.021	-10000	0	-10000	0	0
GAS2	0.007	0.029	-10000	0	-0.23	2	2
positive regulation of apoptosis	0.027	0.017	-10000	0	-10000	0	0
PRF1	0.01	0.001	-10000	0	-10000	0	0

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.004	0.001	-10000	0	-10000	0	0
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.011	0.004	-10000	0	-10000	0	0
STXBP1	0.01	0	-10000	0	-10000	0	0
ACh/CHRNA1	0.004	0.008	-10000	0	-10000	0	0
RAB3GAP2/RIMS1/UNC13B	0.016	0.005	-10000	0	-10000	0	0
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	0.005	0.005	-10000	0	-10000	0	0
mol:ACh	0.014	0.015	0.057	3	-0.11	1	4
RAB3GAP2	0.01	0	-10000	0	-10000	0	0
STX1A/SNAP25/VAMP2	0.009	0.012	-10000	0	-10000	0	0
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	0.004	0.008	-10000	0	-10000	0	0
UNC13B	0.01	0	-10000	0	-10000	0	0
CHRNA1	0.002	0.004	-10000	0	-10000	0	0
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	-0.07	0.13	-10000	0	-0.27	86	86
SNAP25	0.001	0.015	-10000	0	-0.26	1	1
VAMP2	0.003	0	-10000	0	-10000	0	0
SYT1	-0.12	0.2	-10000	0	-0.44	86	86
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.011	0.001	-10000	0	-10000	0	0
STX1A/SNAP25 fragment 1/VAMP2	0.009	0.012	-10000	0	-10000	0	0

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.003	0.06	-9999	-0.22	20	20
FZD6	0.01	0	-9999	-10000	0	0
WNT6	0.007	0.026	-9999	-0.44	1	1
WNT4	-0.004	0.078	-9999	-0.44	9	9
FZD3	0.01	0	-9999	-10000	0	0
WNT5A	0.008	0.003	-9999	-10000	0	0
WNT11	-0.009	0.09	-9999	-0.44	12	12

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.001	0.026	-9999	-10000	0	0
Syndecan-4/Syndesmos	-0.088	0.12	-9999	-0.5	4	4
positive regulation of JNK cascade	-0.1	0.13	-9999	-0.38	21	21
Syndecan-4/ADAM12	-0.088	0.12	-9999	-0.5	4	4
CCL5	0.009	0.003	-9999	-10000	0	0
Rac1/GDP	0.007	0	-9999	-10000	0	0
DNM2	0.01	0	-9999	-10000	0	0
ITGA5	0.01	0	-9999	-10000	0	0
SDCBP	0.01	0	-9999	-10000	0	0
PLG	-0.24	0.21	-9999	-0.43	164	164
ADAM12	0.009	0.003	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.01	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.006	0.007	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.092	0.13	-9999	-0.44	9	9
Syndecan-4/CXCL12/CXCR4	-0.11	0.13	-9999	-0.4	21	21
Syndecan-4/Laminin alpha3	-0.083	0.11	-9999	-0.47	4	4
MDK	0.007	0.004	-9999	-10000	0	0
Syndecan-4/FZD7	-0.093	0.13	-9999	-0.44	7	7
Syndecan-4/Midkine	-0.085	0.11	-9999	-0.47	4	4
FZD7	-0.003	0.074	-9999	-0.44	8	8
Syndecan-4/FGFR1/FGF	-0.088	0.11	-9999	-0.43	6	6
THBS1	-0.007	0.086	-9999	-0.44	11	11
integrin-mediated signaling pathway	-0.087	0.12	-9999	-0.45	6	6
positive regulation of MAPKKK cascade	-0.1	0.13	-9999	-0.38	21	21
Syndecan-4/TACI	-0.093	0.12	-9999	-0.5	4	4
CXCR4	0.009	0.002	-9999	-10000	0	0
cell adhesion	0.018	0.009	-9999	-10000	0	0
Syndecan-4/Dynamin	-0.088	0.12	-9999	-0.5	4	4
Syndecan-4/TSP1	-0.096	0.13	-9999	-0.43	10	10
Syndecan-4/GIPC	-0.088	0.12	-9999	-0.5	4	4
Syndecan-4/RANTES	-0.087	0.12	-9999	-0.5	4	4
ITGB1	0.01	0	-9999	-10000	0	0
LAMA1	-0.003	0.074	-9999	-0.44	8	8
LAMA3	0.007	0.004	-9999	-10000	0	0
RAC1	0.01	0	-9999	-10000	0	0
PRKCA	0.035	0.034	-9999	-10000	0	0
Syndecan-4/alpha-Actinin	-0.088	0.12	-9999	-0.5	4	4
TFPI	0.008	0.026	-9999	-0.44	1	1
F2	0.01	0.007	-9999	-10000	0	0
alpha5/beta1 Integrin	0.015	0	-9999	-10000	0	0
positive regulation of cell adhesion	-0.082	0.11	-9999	-0.41	9	9
ACTN1	0.01	0	-9999	-10000	0	0
TNC	0.003	0.052	-9999	-0.44	4	4
Syndecan-4/CXCL12	-0.11	0.14	-9999	-0.42	21	21
FGF6	0	0.002	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
CXCL12	-0.046	0.15	-9999	-0.44	36	36
TNFRSF13B	0.006	0.005	-9999	-10000	0	0
FGF2	0.005	0.046	-9999	-0.44	3	3
FGFR1	0.01	0	-9999	-10000	0	0
Syndecan-4/PI-4-5-P2	-0.1	0.11	-9999	-0.51	4	4
mol:GDP	0	0	-9999	-10000	0	0
FN1	0.013	0.007	-9999	-10000	0	0
cell migration	0.002	0.004	-9999	-10000	0	0
PRKCD	0.013	0.007	-9999	-10000	0	0
vasculogenesis	-0.093	0.13	-9999	-0.42	10	10
SDC4	-0.095	0.12	-9999	-0.53	4	4
Syndecan-4/Tenascin C	-0.089	0.12	-9999	-0.47	6	6
Syndecan-4/PI-4-5-P2/PKC alpha	-0.005	0.006	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.088	0.12	-9999	-0.5	4	4
MMP9	0.002	0.052	-9999	-0.43	4	4
Rac1/GTP	0.018	0.009	-9999	-10000	0	0
cytoskeleton organization	-0.086	0.12	-9999	-0.49	4	4
GIPC1	0.01	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.088	0.12	-9999	-0.5	4	4

×

Class IB PI3K non-lipid kinase events

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

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

Entity	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	0.064	0.44	6	-10000	0	6
PI3K Class IB/PDE3B	0.064	-10000	0	-0.44	6	6
PDE3B	0.064	-10000	0	-0.44	6	6

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.012	0.004	-9999	-10000	0	0
EPHB2	0.01	0.001	-9999	-10000	0	0
Syndecan-2/TACI	0.01	0.004	-9999	-10000	0	0
LAMA1	-0.003	0.074	-9999	-0.44	8	8
Syndecan-2/alpha2 ITGB1	0.015	0.026	-9999	-0.22	3	3
HRAS	0.01	0	-9999	-10000	0	0
Syndecan-2/CASK	0.006	0.001	-9999	-10000	0	0
ITGA5	0.01	0	-9999	-10000	0	0
BAX	0.009	0.031	-9999	-10000	0	0
EPB41	0.01	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	0.012	0.001	-9999	-10000	0	0
LAMA3	0.007	0.004	-9999	-10000	0	0
EZR	0.01	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	0.01	0.001	-9999	-10000	0	0
Syndecan-2/MMP2	0.012	0.016	-9999	-0.26	1	1
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	0.011	0.033	-9999	-0.31	3	3
dendrite morphogenesis	0.013	0.002	-9999	-10000	0	0
Syndecan-2/GM-CSF	0.009	0.004	-9999	-10000	0	0
determination of left/right symmetry	0.009	0.005	-9999	-10000	0	0
Syndecan-2/PKC delta	0.013	0.001	-9999	-10000	0	0
GNB2L1	0.01	0	-9999	-10000	0	0
MAPK3	0.01	0.005	-9999	-10000	0	0
MAPK1	0.01	0.005	-9999	-10000	0	0
Syndecan-2/RACK1	0.018	0.003	-9999	-10000	0	0
NF1	0.01	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.009	0.005	-9999	-10000	0	0
ITGA2	0.005	0.046	-9999	-0.44	3	3
MAPK8	0.007	0.035	-9999	-0.26	5	5
Syndecan-2/alpha2/beta1 Integrin	0.014	0.046	-9999	-0.22	11	11
Syndecan-2/Kininogen	-0.15	0.13	-9999	-0.26	169	169
ITGB1	0.01	0	-9999	-10000	0	0
SRC	0.013	0.004	-9999	-10000	0	0
Syndecan-2/CASK/Protein 4.1	0.012	0.001	-9999	-10000	0	0
extracellular matrix organization	0.013	0.002	-9999	-10000	0	0
actin cytoskeleton reorganization	0.012	0.004	-9999	-10000	0	0
Syndecan-2/Caveolin-2/Ras	0.019	0.004	-9999	-10000	0	0
Syndecan-2/Laminin alpha3	0.009	0.006	-9999	-10000	0	0
Syndecan-2/RasGAP	0.023	0.003	-9999	-10000	0	0
alpha5/beta1 Integrin	0.015	0	-9999	-10000	0	0
PRKCD	0.01	0	-9999	-10000	0	0
Syndecan-2 dimer	0.013	0.002	-9999	-10000	0	0
GO:0007205	0.002	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.021	0.004	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
SDCBP	0.01	0	-9999	-10000	0	0
TNFRSF13B	0.006	0.005	-9999	-10000	0	0
RASA1	0.01	0	-9999	-10000	0	0
alpha2/beta1 Integrin	0.011	0.033	-9999	-0.31	3	3
Syndecan-2/Synbindin	0.013	0.001	-9999	-10000	0	0
TGFB1	0.01	0.001	-9999	-10000	0	0
CASP3	0.012	0.004	-9999	-10000	0	0
FN1	0.009	0.003	-9999	-10000	0	0
Syndecan-2/IL8	0.009	0.017	-9999	-0.26	1	1
SDC2	0.009	0.005	-9999	-10000	0	0
KNG1	-0.26	0.22	-9999	-0.44	169	169
Syndecan-2/Neurofibromin	0.013	0.001	-9999	-10000	0	0
TRAPPC4	0.01	0	-9999	-10000	0	0
CSF2	0.004	0.005	-9999	-10000	0	0
Syndecan-2/TGFB1	0.013	0.002	-9999	-10000	0	0
Syndecan-2/Syntenin/PI-4-5-P2	0.012	0.001	-9999	-10000	0	0
Syndecan-2/Ezrin	0.019	0.004	-9999	-10000	0	0
PRKACA	0.012	0.004	-9999	-10000	0	0
angiogenesis	0.009	0.017	-9999	-0.26	1	1
MMP2	0.008	0.026	-9999	-0.44	1	1
IL8	0.006	0.027	-9999	-0.44	1	1
calcineurin-NFAT signaling pathway	0.01	0.004	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	0.013	0.005	-9999	-10000	0	0
CRKL	0.009	0.046	-9999	-10000	0	0
mol:PIP3	-0.005	0.003	-9999	-10000	0	0
AKT1	-0.001	0.002	-9999	-10000	0	0
PTK2B	0.01	0	-9999	-10000	0	0
RAPGEF1	0.01	0.044	-9999	-10000	0	0
RANBP10	0.01	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
HGF/MET/SHIP2	0.003	0.06	-9999	-0.24	17	17
MAP3K5	0.017	0.043	-9999	-10000	0	0
HGF/MET/CIN85/CBL/ENDOPHILINS	0.009	0.056	-9999	-0.21	17	17
AP1	-0.027	0.1	-9999	-0.27	44	44
mol:SU11274	0	0	-9999	-10000	0	0
SHC1	0.01	0	-9999	-10000	0	0
apoptosis	-0.091	0.26	-9999	-0.7	44	44
STAT3 (dimer)	0.008	0.054	-9999	-0.21	12	12
GAB1/CRKL/SHP2/PI3K	0.022	0.044	-9999	-10000	0	0
INPP5D	0.009	0.002	-9999	-10000	0	0
CBL/CRK	0.014	0.045	-9999	-10000	0	0
PTPN11	0.01	0	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
PLCG1	0.01	0	-9999	-10000	0	0
PTEN	0.01	0	-9999	-10000	0	0
ELK1	0.006	0.027	-9999	-10000	0	0
mol:SU5416	0	0	-9999	-10000	0	0
SHP2/GRB2/SOS1GAB1	0.004	0.032	-9999	-10000	0	0
PAK1	0.001	0.002	-9999	-10000	0	0
HGF/MET/RANBP10	0.003	0.06	-9999	-0.24	17	17
HRAS	0.001	0.06	-9999	-10000	0	0
DOCK1	0.01	0.044	-9999	-10000	0	0
GAB1	0.008	0.048	-9999	-10000	0	0
CRK	0.009	0.046	-9999	-10000	0	0
mol:PHA665752	0	0	-9999	-10000	0	0
mol:GDP	-0.01	0.1	-9999	-0.42	17	17
JUN	0.01	0	-9999	-10000	0	0
EntrezGene:200958	0	0	-9999	-10000	0	0
HGF/MET	-0.003	0.039	-9999	-0.16	17	17
PIK3R1	0.01	0	-9999	-10000	0	0
cell morphogenesis	0.013	0.057	-9999	-0.22	12	12
GRB2/SHC	0.013	0.039	-9999	-0.15	12	12
FOS	-0.058	0.16	-9999	-0.44	44	44
GLMN	0.002	0	-9999	-10000	0	0
cell motility	0.006	0.027	-9999	-10000	0	0
HGF/MET/MUC20	-0.003	0.059	-9999	-0.24	17	17
cell migration	0.007	0.037	-9999	-0.15	12	12
GRB2	0.01	0	-9999	-10000	0	0
CBL	0.01	0	-9999	-10000	0	0
MET/RANBP10	0.013	0.005	-9999	-10000	0	0
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.002	0.052	-9999	-0.2	17	17
MET/MUC20	0.006	0.002	-9999	-10000	0	0
RAP1B	0.011	0.042	-9999	-10000	0	0
RAP1A	0.011	0.042	-9999	-10000	0	0
HGF/MET/RANBP9	0.003	0.06	-9999	-0.24	17	17
RAF1	0.007	0.058	-9999	-10000	0	0
STAT3	0.002	0.052	-9999	-0.22	12	12
cell proliferation	0.005	0.074	-9999	-0.29	17	17
RPS6KB1	0.006	0.017	-9999	-10000	0	0
MAPK3	0.002	0.025	-9999	-10000	0	0
MAPK1	0.002	0.025	-9999	-10000	0	0
RANBP9	0.01	0	-9999	-10000	0	0
MAPK8	0.015	0.068	-9999	-0.41	5	5
SRC	0.002	0.048	-9999	-0.2	12	12
PI3K	0.013	0.039	-9999	-0.15	12	12
MET/Glomulin	0.008	0.003	-9999	-10000	0	0
SOS1	0.01	0	-9999	-10000	0	0
MAP2K1	0.008	0.055	-9999	-10000	0	0
MET	0.009	0.003	-9999	-10000	0	0
MAP4K1	0.016	0.045	-9999	-10000	0	0
PTK2	0.01	0	-9999	-10000	0	0
MAP2K2	0.008	0.055	-9999	-10000	0	0
BAD	0.001	0.002	-9999	-10000	0	0
MAP2K4	0.017	0.04	-9999	-10000	0	0
SHP2/GRB2/SOS1/GAB1	0.01	0.041	-9999	-10000	0	0
INPPL1	0.01	0	-9999	-10000	0	0
PXN	0.01	0	-9999	-10000	0	0
SH3KBP1	0.01	0	-9999	-10000	0	0
HGS	-0.002	0.036	-9999	-0.16	12	12
PLCgamma1/PKC	0.007	0	-9999	-10000	0	0
HGF	-0.017	0.11	-9999	-0.44	17	17
RASA1	0.01	0	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
PTPRJ	0.01	0	-9999	-10000	0	0
NCK/PLCgamma1	0.012	0.043	-9999	-0.17	12	12
PDPK1	-0.002	0.003	-9999	-10000	0	0
HGF/MET/SHIP	0.002	0.06	-9999	-0.24	17	17

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.009	0.003	-9999	-10000	0	0
PRKCZ	0.01	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
ERC1	0.01	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	0.012	0.02	-9999	-10000	0	0
IRAK/TOLLIP	0.015	0.001	-9999	-10000	0	0
IKBKB	0.01	0	-9999	-10000	0	0
IKBKG	0.01	0	-9999	-10000	0	0
IL1 alpha/IL1R2	-0.071	0.14	-9999	-0.3	76	76
IL1A	0.008	0.004	-9999	-10000	0	0
IL1B	0.003	0.042	-9999	-0.31	5	5
IRAK/TRAF6/p62/Atypical PKCs	0.027	0.005	-9999	-10000	0	0
IL1R2	-0.11	0.2	-9999	-0.44	76	76
IL1R1	0.01	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.013	0.018	-9999	-10000	0	0
TOLLIP	0.01	0	-9999	-10000	0	0
TICAM2	0.008	0.026	-9999	-0.44	1	1
MAP3K3	0.01	0	-9999	-10000	0	0
TAK1/TAB1/TAB2	0.007	0	-9999	-10000	0	0
IKK complex/ELKS	0.025	0.004	-9999	-10000	0	0
JUN	0.007	0.025	-9999	-0.18	5	5
MAP3K7	0.01	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.024	0.031	-9999	-0.2	5	5
IL1 alpha/IL1R1/IL1RAP/MYD88	0.021	0.009	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.025	0.01	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP	0.015	0.033	-9999	-0.23	5	5
NFKB1	0.01	0	-9999	-10000	0	0
MAPK8	0.007	0.027	-9999	-0.2	5	5
IRAK1	0.009	0.001	-9999	-10000	0	0
IL1RN/IL1R1	0.013	0.019	-9999	-0.31	1	1
IRAK4	0.01	0	-9999	-10000	0	0
PRKCI	0.01	0	-9999	-10000	0	0
TRAF6	0.01	0	-9999	-10000	0	0
PI3K	0.015	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.015	0.022	-9999	-10000	0	0
CHUK	0.01	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.015	0.033	-9999	-0.23	5	5
IL1 beta/IL1R2	-0.061	0.12	-9999	-0.26	80	80
IRAK/TRAF6/TAK1/TAB1/TAB2	0.017	0.001	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.017	0.027	-9999	-0.19	5	5
IRAK3	0.01	0.001	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.023	0.038	-9999	-0.25	5	5
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.014	0.006	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP	0.017	0.007	-9999	-10000	0	0
RELA	0.01	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
SQSTM1	0.009	0.002	-9999	-10000	0	0
MYD88	0.01	0	-9999	-10000	0	0
IRAK/TRAF6/MEKK3	0.02	0.001	-9999	-10000	0	0
IL1RAP	0.01	0.001	-9999	-10000	0	0
UBE2N	0.01	0	-9999	-10000	0	0
IRAK/TRAF6	0.012	0.031	-9999	-0.36	1	1
CASP1	0.01	0.001	-9999	-10000	0	0
IL1RN/IL1R2	-0.071	0.14	-9999	-0.31	77	77
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.02	0.031	-9999	-0.22	5	5
TMEM189-UBE2V1	0.002	0.004	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.016	0.006	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
IL1RN	0.008	0.026	-9999	-0.44	1	1
TRAF6/TAK1/TAB1/TAB2	0.015	0.002	-9999	-10000	0	0
MAP2K6	0.011	0.001	-9999	-10000	0	0

×

BCR signaling pathway

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
JUN	0.024	0.051	-10000	0	-0.29	4	4
IKBKB	0.027	0.042	-10000	0	-0.21	1	1
AKT1	0.023	0.043	0.15	7	-0.18	4	11
IKBKG	0.026	0.043	-10000	0	-0.19	3	3
CALM1	-0.002	0.075	0.17	8	-0.32	10	18
PIK3CA	0.01	0	-10000	0	-10000	0	0
MAP3K1	0.031	0.062	-10000	0	-0.42	3	3
MAP3K7	0.01	0	-10000	0	-10000	0	0
mol:Ca2+	-0.004	0.079	0.17	8	-0.34	10	18
DOK1	0.01	0.001	-10000	0	-10000	0	0
AP-1	0	0.059	0.13	1	-0.18	12	13
LYN	0.01	0	-10000	0	-10000	0	0
BLNK	-0.006	0.082	-10000	0	-0.44	10	10
SHC1	0.01	0	-10000	0	-10000	0	0
BCR complex	0.007	0.042	-10000	0	-0.31	5	5
CD22	0	0.051	-10000	0	-0.33	6	6
CAMK2G	-0.001	0.071	-10000	0	-0.31	9	9
CSNK2A1	0.01	0	-10000	0	-10000	0	0
INPP5D	0.009	0.002	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0	0.049	-10000	0	-0.2	15	15
GO:0007205	-0.004	0.08	0.17	8	-0.34	10	18
SYK	0.008	0.026	-10000	0	-0.44	1	1
ELK1	-0.003	0.076	0.17	8	-0.32	10	18
NFATC1	0.019	0.056	-10000	0	-0.3	5	5
B-cell antigen/BCR complex	0.007	0.042	-10000	0	-0.31	5	5
PAG1/CSK	0.015	0	-10000	0	-10000	0	0
NFKBIB	0.018	0.017	-10000	0	-10000	0	0
HRAS	-0.002	0.069	-10000	0	-0.3	10	10
NFKBIA	0.018	0.017	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.02	0.015	-10000	0	-10000	0	0
RasGAP/Csk	0.013	0.036	-10000	0	-0.22	6	6
mol:GDP	-0.007	0.078	0.17	8	-0.33	10	18
PTEN	0.01	0	-10000	0	-10000	0	0
CD79B	0.005	0.045	-10000	0	-0.44	3	3
NF-kappa-B/RelA/I kappa B alpha	0.02	0.015	-10000	0	-10000	0	0
GRB2	0.01	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	0.026	0.081	-10000	0	-0.48	4	4
PIK3R1	0.01	0	-10000	0	-10000	0	0
mol:IP3	-0.003	0.081	0.17	8	-0.34	10	18
CSK	0.01	0	-10000	0	-10000	0	0
FOS	-0.031	0.11	0.16	6	-0.24	45	51
CHUK	0.026	0.043	-10000	0	-0.19	3	3
IBTK	0.01	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	0	0.062	-10000	0	-0.33	7	7
PTPN6	0.009	0.051	-10000	0	-0.32	6	6
RELA	0.01	0	-10000	0	-10000	0	0
BCL2A1	0.017	0.018	-10000	0	-10000	0	0
VAV2	0.01	0.058	-10000	0	-0.38	5	5
ubiquitin-dependent protein catabolic process	0.019	0.016	-10000	0	-10000	0	0
BTK	-0.003	0.03	-10000	0	-10000	0	0
CD19	0.001	0.052	-10000	0	-0.36	5	5
MAP4K1	0.008	0.003	-10000	0	-10000	0	0
CD72	0.009	0.002	-10000	0	-10000	0	0
PAG1	0.01	0	-10000	0	-10000	0	0
MAPK14	0.031	0.056	-10000	0	-0.36	3	3
SH3BP5	-0.009	0.09	-10000	0	-0.44	12	12
PIK3AP1	-0.001	0.083	0.19	8	-0.34	10	18
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.004	0.093	-10000	0	-0.43	10	10
RAF1	0	0.066	-10000	0	-0.28	10	10
RasGAP/p62DOK/SHIP	0.013	0.035	-10000	0	-0.2	6	6
CD79A	0.005	0.037	-10000	0	-0.44	2	2
re-entry into mitotic cell cycle	0	0.059	0.13	1	-0.18	12	13
RASA1	0.01	0	-10000	0	-10000	0	0
MAPK3	0.003	0.057	-10000	0	-0.27	7	7
MAPK1	0.003	0.057	-10000	0	-0.27	7	7
CD72/SHP1	0.025	0.055	-10000	0	-0.3	6	6
NFKB1	0.01	0	-10000	0	-10000	0	0
MAPK8	0.028	0.061	-10000	0	-0.36	3	3
actin cytoskeleton organization	0.025	0.061	-10000	0	-0.33	5	5
NF-kappa-B/RelA	0.041	0.03	-10000	0	-10000	0	0
Calcineurin	0.006	0.063	-10000	0	-0.32	7	7
PI3K	-0.008	0.04	-10000	0	-0.3	4	4
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.006	0.085	0.2	8	-0.36	10	18
SOS1	0.01	0	-10000	0	-10000	0	0
Bam32/HPK1	0.016	0.076	-10000	0	-0.57	4	4
DAPP1	0.009	0.082	-10000	0	-0.63	4	4
cytokine secretion	0.019	0.053	-10000	0	-0.29	5	5
mol:DAG	-0.003	0.081	0.17	8	-0.34	10	18
PLCG2	-0.015	0.1	-10000	0	-0.44	16	16
MAP2K1	0.002	0.062	-10000	0	-0.3	7	7
B-cell antigen/BCR complex/FcgammaRIIB	0.007	0.04	-10000	0	-0.26	6	6
mol:PI-3-4-5-P3	-0.001	0.032	-10000	0	-0.22	4	4
ETS1	0.001	0.066	-10000	0	-0.32	7	7
B-cell antigen/BCR complex/LYN/SYK/BLNK	0.012	0.059	-10000	0	-0.23	15	15
B-cell antigen/BCR complex/LYN	0	0.056	-10000	0	-0.36	6	6
MALT1	0.01	0	-10000	0	-10000	0	0
TRAF6	0.01	0	-10000	0	-10000	0	0
RAC1	0.025	0.064	-10000	0	-0.38	4	4
B-cell antigen/BCR complex/LYN/SYK	0.011	0.052	-10000	0	-0.32	5	5
CARD11	0.015	0.084	0.17	8	-0.32	10	18
FCGR2B	0.005	0.027	-10000	0	-0.44	1	1
PPP3CA	0.01	0	-10000	0	-10000	0	0
BCL10	0.01	0	-10000	0	-10000	0	0
IKK complex	0.02	0.021	0.081	3	-10000	0	3
PTPRC	0.008	0.026	-10000	0	-0.44	1	1
PDPK1	0.021	0.038	0.14	7	-0.16	4	11
PPP3CB	0.01	0	-10000	0	-10000	0	0
PPP3CC	0.01	0	-10000	0	-10000	0	0
POU2F2	0.016	0.012	-10000	0	-10000	0	0

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.001	0.069	-9999	-0.36	10	10
PDGFB-D/PDGFRB/SLAP	0.004	0.058	-9999	-0.3	10	10
PDGFB-D/PDGFRB/APS/CBL	0.011	0.05	-9999	-0.26	10	10
AKT1	0.011	0.035	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	-0.002	0.075	-9999	-0.39	10	10
PIK3CA	0.01	0	-9999	-10000	0	0
FGR	-0.006	0.058	-9999	-0.29	11	11
mol:Ca2+	0.012	0.084	-9999	-0.43	10	10
MYC	0.031	0.063	-9999	-10000	0	0
SHC1	0.01	0	-9999	-10000	0	0
HRAS/GDP	0.011	0.041	-9999	-0.2	10	10
LRP1/PDGFRB/PDGFB	0.01	0.053	-9999	-0.26	11	11
GRB10	0.01	0	-9999	-10000	0	0
PTPN11	0.01	0	-9999	-10000	0	0
GO:0007205	0.011	0.086	-9999	-0.44	10	10
PTEN	0.01	0	-9999	-10000	0	0
GRB2	0.01	0	-9999	-10000	0	0
GRB7	0.01	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHP2	0.004	0.059	-9999	-0.31	10	10
PDGFB-D/PDGFRB/GRB10	0.004	0.059	-9999	-0.31	10	10
cell cycle arrest	0.004	0.057	-9999	-0.3	10	10
HRAS	0.01	0	-9999	-10000	0	0
HIF1A	0.011	0.032	-9999	-10000	0	0
GAB1	0.022	0.08	-9999	-0.39	10	10
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.025	0.075	-9999	-0.36	10	10
PDGFB-D/PDGFRB	0.013	0.052	-9999	-0.26	10	10
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.004	0.059	-9999	-0.31	10	10
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.002	0.063	-9999	-0.33	10	10
positive regulation of MAPKKK cascade	0.004	0.059	-9999	-0.31	10	10
PIK3R1	0.01	0	-9999	-10000	0	0
mol:IP3	0.012	0.086	-9999	-0.44	10	10
E5	0	0.001	-9999	-10000	0	0
CSK	0.009	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	0.004	0.059	-9999	-0.31	10	10
SHB	0.01	0	-9999	-10000	0	0
BLK	-0.005	0.051	-9999	-0.27	10	10
PTPN2	0.01	0.002	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.004	0.059	-9999	-0.31	10	10
BCAR1	0.01	0	-9999	-10000	0	0
VAV2	0.025	0.081	-9999	-0.38	10	10
CBL	0.01	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.004	0.059	-9999	-0.31	10	10
LCK	-0.004	0.051	-9999	-0.27	10	10
PDGFRB	-0.005	0.083	-9999	-0.44	10	10
ACP1	0.01	0	-9999	-10000	0	0
HCK	-0.006	0.058	-9999	-0.29	11	11
ABL1	0.018	0.068	-9999	-0.33	10	10
PDGFB-D/PDGFRB/CBL	0.018	0.092	-9999	-0.46	10	10
PTPN1	0.01	0.002	-9999	-10000	0	0
SNX15	0.01	0	-9999	-10000	0	0
STAT3	0.01	0	-9999	-10000	0	0
STAT1	0.01	0.001	-9999	-10000	0	0
cell proliferation	0.031	0.06	-9999	-10000	0	0
SLA	0.009	0.002	-9999	-10000	0	0
actin cytoskeleton reorganization	0.014	0.04	-9999	-0.2	10	10
SRC	-0.004	0.051	-9999	-0.27	10	10
PI3K	-0.006	0.034	-9999	-0.19	10	10
PDGFB-D/PDGFRB/GRB7/SHC	0.011	0.05	-9999	-0.26	10	10
SH2B2	0.01	0.001	-9999	-10000	0	0
PLCgamma1/SPHK1	-0.002	0.077	-9999	-0.4	10	10
LYN	-0.004	0.051	-9999	-0.27	10	10
LRP1	0.01	0	-9999	-10000	0	0
SOS1	0.01	0	-9999	-10000	0	0
STAT5B	0.01	0	-9999	-10000	0	0
STAT5A	0.01	0	-9999	-10000	0	0
NCK1-2/p130 Cas	0.024	0.043	-9999	-0.2	10	10
SPHK1	0.005	0.005	-9999	-10000	0	0
EDG1	0.001	0.001	-9999	-10000	0	0
mol:DAG	0.012	0.086	-9999	-0.44	10	10
PLCG1	0.011	0.088	-9999	-0.45	10	10
NHERF/PDGFRB	0.011	0.05	-9999	-0.26	10	10
YES1	-0.004	0.051	-9999	-0.27	10	10
cell migration	0.011	0.05	-9999	-0.26	10	10
SHC/Grb2/SOS1	0.024	0.043	-9999	-0.2	10	10
SLC9A3R2	0.01	0	-9999	-10000	0	0
SLC9A3R1	0.01	0	-9999	-10000	0	0
NHERF1-2/PDGFRB/PTEN	0.017	0.047	-9999	-0.23	10	10
FYN	-0.004	0.051	-9999	-0.27	10	10
DOK1	0.005	0.045	-9999	-0.23	10	10
HRAS/GTP	0.007	0	-9999	-10000	0	0
PDGFB	0.008	0.026	-9999	-0.44	1	1
RAC1	0.026	0.075	-9999	-0.35	10	10
PRKCD	0.006	0.045	-9999	-0.23	10	10
FER	0.006	0.045	-9999	-0.23	10	10
MAPKKK cascade	-0.007	0.037	-9999	-0.2	10	10
RASA1	0.006	0.045	-9999	-0.23	10	10
NCK1	0.01	0	-9999	-10000	0	0
NCK2	0.01	0	-9999	-10000	0	0
p62DOK/Csk	0.009	0.042	-9999	-0.21	10	10
PDGFB-D/PDGFRB/SHB	0.004	0.059	-9999	-0.31	10	10
chemotaxis	0.018	0.067	-9999	-0.32	10	10
STAT1-3-5/STAT1-3-5	0.017	0.041	-9999	-0.2	10	10
Bovine Papilomavirus E5/PDGFRB	-0.002	0.059	-9999	-0.31	10	10
PTPRJ	0.01	0	-9999	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.021	0.13	-9999	-0.32	44	44
MAP3K8	0.008	0.006	-9999	-10000	0	0
FOS	-0.007	0.076	-9999	-0.59	1	1
PRKCA	0.007	0.008	-9999	-10000	0	0
PTPN7	0.004	0.029	-9999	-0.45	1	1
HRAS	0.009	0.001	-9999	-10000	0	0
PRKCB	0.007	0.008	-9999	-10000	0	0
NRAS	0.009	0.001	-9999	-10000	0	0
RAS family/GTP	0.015	0.011	-9999	-10000	0	0
MAPK3	0.003	0.046	-9999	-0.5	1	1
MAP2K1	0.006	0.03	-9999	-10000	0	0
ELK1	0.005	0.012	-9999	-10000	0	0
BRAF	0.007	0.018	-9999	-10000	0	0
mol:GTP	-0.001	0.002	-9999	-0.005	44	44
MAPK1	0.003	0.046	-9999	-0.5	1	1
RAF1	0.007	0.018	-9999	-10000	0	0
KRAS	0.009	0.001	-9999	-10000	0	0

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.01	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.025	0.091	-9999	-0.19	64	64
Syndecan-3/Neurocan	0.011	0.006	-9999	-10000	0	0
POMC	0.004	0.052	-9999	-0.44	4	4
EGFR	0.01	0	-9999	-10000	0	0
Syndecan-3/EGFR	0.014	0.004	-9999	-10000	0	0
AGRP	0.007	0.005	-9999	-10000	0	0
NCSTN	0.01	0	-9999	-10000	0	0
PSENEN	0.01	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.008	0.026	-9999	-0.44	1	1
APH1A	0.01	0	-9999	-10000	0	0
NCAN	0.007	0.005	-9999	-10000	0	0
long-term memory	0.019	0.004	-9999	-10000	0	0
Syndecan-3/IL8	0.01	0.015	-9999	-0.21	1	1
PSEN1	0.01	0	-9999	-10000	0	0
Src/Cortactin	0.015	0.001	-9999	-10000	0	0
FYN	0.01	0	-9999	-10000	0	0
limb bud formation	0.008	0.004	-9999	-10000	0	0
MC4R	0.002	0.004	-9999	-10000	0	0
SRC	0.01	0.001	-9999	-10000	0	0
PTN	-0.091	0.19	-9999	-0.44	65	65
FGFR/FGF/Syndecan-3	0.008	0.004	-9999	-10000	0	0
neuron projection morphogenesis	-0.03	0.082	-9999	-0.24	1	1
Syndecan-3/AgRP	0.012	0.005	-9999	-10000	0	0
Syndecan-3/AgRP/MC4R	0.012	0.006	-9999	-10000	0	0
Fyn/Cortactin	0.015	0	-9999	-10000	0	0
SDC3	0.008	0.004	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	0.01	0.014	-9999	-0.21	1	1
IL8	0.006	0.027	-9999	-0.44	1	1
Syndecan-3/Fyn/Cortactin	0.019	0.004	-9999	-10000	0	0
Syndecan-3/CASK	0.007	0.003	-9999	-10000	0	0
alpha-MSH/MC4R	0.005	0.038	-9999	-0.31	4	4
Gamma Secretase	0.028	0.014	-9999	-0.22	1	1

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.013	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.01	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.01	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.01	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.011	0.001	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
YES1	0.01	0	-9999	-10000	0	0
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.01	0	-9999	-10000	0	0
FYN	0.01	0	-9999	-10000	0	0
MAP3K12	0.01	0.001	-9999	-10000	0	0
FGR	0.008	0.026	-9999	-0.44	1	1
p38 alpha/TAB1	-0.001	0.011	-9999	-0.19	1	1
PRKG1	-0.1	0.2	-9999	-0.44	73	73
DUSP8	0.01	0	-9999	-10000	0	0
PGK/cGMP/p38 alpha	-0.027	0.083	-9999	-0.17	64	64
apoptosis	-0.001	0.011	-9999	-0.18	1	1
RAL/GTP	0.013	0	-9999	-10000	0	0
LYN	0.01	0	-9999	-10000	0	0
DUSP1	0.008	0.026	-9999	-0.44	1	1
PAK1	0.01	0	-9999	-10000	0	0
SRC	0.01	0.001	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.025	0	-9999	-10000	0	0
TRAF6	0.01	0	-9999	-10000	0	0
RAC1	0.01	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0.01	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0.013	0	-9999	-10000	0	0
MAPK11	0.03	0.021	-9999	-0.27	1	1
BLK	0.008	0.004	-9999	-10000	0	0
HCK	0.007	0.026	-9999	-0.44	1	1
MAP2K3	0.01	0	-9999	-10000	0	0
DUSP16	0.01	0	-9999	-10000	0	0
DUSP10	0.009	0.003	-9999	-10000	0	0
TRAF6/MEKK3	0.013	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.028	0.016	-9999	-0.2	1	1
positive regulation of innate immune response	0.035	0.023	-9999	-0.3	1	1
LCK	0.01	0.001	-9999	-10000	0	0
p38alpha-beta/MKP7	0.039	0.022	-9999	-0.28	1	1
p38alpha-beta/MKP5	0.035	0.024	-9999	-0.28	1	1
PGK/cGMP	-0.073	0.14	-9999	-0.31	73	73
PAK2	0.01	0	-9999	-10000	0	0
p38alpha-beta/MKP1	0.038	0.025	-9999	-0.28	1	1
CDC42	0.01	0	-9999	-10000	0	0
RALB	0.01	0	-9999	-10000	0	0
RALA	0.01	0	-9999	-10000	0	0
PAK3	0.008	0.004	-9999	-10000	0	0

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.022	0.014	-10000	0	-0.21	1	1
NF kappa B1 p50/RelA/I kappa B alpha	0.015	0.038	-10000	0	-10000	0	0
AP1	-0.009	0.084	-10000	0	-0.2	44	44
mol:PIP3	-0.001	0.01	-10000	0	-10000	0	0
AKT1	0.02	0.014	-10000	0	-10000	0	0
PTK2B	0.008	0.02	-10000	0	-0.17	1	1
RHOA	0.01	0.011	-10000	0	-10000	0	0
PIK3CB	0.01	0.001	-10000	0	-10000	0	0
mol:Ca2+	-0.006	0.045	0.14	1	-0.19	1	2
MAGI3	0.01	0	-10000	0	-10000	0	0
RELA	0.01	0	-10000	0	-10000	0	0
apoptosis	0.01	0.013	-10000	0	-0.21	1	1
HRAS/GDP	0.007	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.003	0.038	-10000	0	-0.18	9	9
NF kappa B1 p50/RelA	0.01	0.043	-10000	0	-10000	0	0
endothelial cell migration	0.01	0.032	-10000	0	-0.54	1	1
ADCY4	-0.01	0.077	-10000	0	-0.4	5	5
ADCY5	-0.01	0.071	-10000	0	-0.4	3	3
ADCY6	0.001	0.055	-10000	0	-0.39	1	1
ADCY7	0	0.055	-10000	0	-0.39	1	1
ADCY1	-0.085	0.12	-10000	0	-0.39	19	19
ADCY2	-0.006	0.05	-10000	0	-0.37	1	1
ADCY3	0.001	0.055	-10000	0	-0.39	1	1
ADCY8	0	0.055	-10000	0	-0.4	1	1
ADCY9	0.001	0.055	-10000	0	-0.39	1	1
GSK3B	0.009	0.019	-10000	0	-0.16	1	1
arachidonic acid secretion	-0.001	0.063	-10000	0	-0.2	25	25
GNG2	0.01	0	-10000	0	-10000	0	0
TRIP6	0.012	0.005	-10000	0	-10000	0	0
GNAO1	-0.011	0.08	-10000	0	-0.27	25	25
HRAS	0.01	0	-10000	0	-10000	0	0
NFKBIA	0.004	0.037	-10000	0	-10000	0	0
GAB1	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	0.018	0	-10000	0	-10000	0	0
JUN	0.01	0	-10000	0	-10000	0	0
LPA/LPA2/NHERF2	0.015	0.006	-10000	0	-10000	0	0
TIAM1	0.014	0.002	-10000	0	-10000	0	0
PIK3R1	0.01	0	-10000	0	-10000	0	0
mol:IP3	-0.006	0.045	0.14	1	-0.2	1	2
PLCB3	0.012	0.007	-10000	0	-10000	0	0
FOS	-0.058	0.16	-10000	0	-0.44	44	44
positive regulation of mitosis	-0.001	0.063	-10000	0	-0.2	25	25
LPA/LPA1-2-3	0.019	0.015	-10000	0	-0.21	1	1
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0	-10000	0	-10000	0	0
BCAR1	0.01	0	-10000	0	-10000	0	0
stress fiber formation	0.014	0.019	-10000	0	-0.17	1	1
GNAZ	0.012	0.019	-10000	0	-0.23	1	1
EGFR/PI3K-beta/Gab1	0.007	0.011	-10000	0	-10000	0	0
positive regulation of dendritic cell cytokine production	0.019	0.014	-10000	0	-0.21	1	1
LPA/LPA2/MAGI-3	0.014	0.006	-10000	0	-10000	0	0
ARHGEF1	0.015	0.017	-10000	0	-0.19	1	1
GNAI2	0.012	0.019	-10000	0	-0.23	1	1
GNAI3	0.012	0.019	-10000	0	-0.23	1	1
GNAI1	0.01	0.029	-10000	0	-0.25	3	3
LPA/LPA3	0.004	0.007	-10000	0	-0.11	1	1
LPA/LPA2	0.009	0.007	-10000	0	-0.1	1	1
LPA/LPA1	0.011	0.017	-10000	0	-0.28	1	1
HB-EGF/EGFR	0.004	0.039	-10000	0	-0.26	6	6
HBEGF	-0.001	0.045	-10000	0	-0.31	6	6
mol:DAG	-0.006	0.045	0.14	1	-0.2	1	2
cAMP biosynthetic process	-0.017	0.073	-10000	0	-0.24	25	25
NFKB1	0.01	0	-10000	0	-10000	0	0
SRC	0.01	0.001	-10000	0	-10000	0	0
GNB1	0.01	0	-10000	0	-10000	0	0
LYN	0.004	0.037	-10000	0	-10000	0	0
GNAQ	0.01	0.007	-10000	0	-10000	0	0
LPAR2	0.01	0.001	-10000	0	-10000	0	0
LPAR3	0.004	0.005	-10000	0	-10000	0	0
LPAR1	0.011	0.01	-10000	0	-0.16	1	1
IL8	0.051	0.11	0.22	40	-0.32	6	46
PTK2	0.015	0.018	-10000	0	-0.19	1	1
Rac1/GDP	0.007	0	-10000	0	-10000	0	0
CASP3	0.01	0.013	-10000	0	-0.21	1	1
EGFR	0.01	0.001	-10000	0	-10000	0	0
PLCG1	-0.014	0.05	-10000	0	-0.23	1	1
PLD2	0.015	0.018	-10000	0	-0.19	1	1
G12/G13	0.022	0.014	-10000	0	-0.21	1	1
PI3K-beta	-0.001	0.009	-10000	0	-10000	0	0
cell migration	0.021	0.009	-10000	0	-10000	0	0
SLC9A3R2	0.01	0	-10000	0	-10000	0	0
PXN	0.015	0.019	-10000	0	-0.17	1	1
HRAS/GTP	-0.002	0.064	-10000	0	-0.2	25	25
RAC1	0.01	0	-10000	0	-10000	0	0
MMP9	0	0.052	-10000	0	-0.44	4	4
PRKCE	0.01	0	-10000	0	-10000	0	0
PRKCD	-0.004	0.043	-10000	0	-0.19	1	1
Gi(beta/gamma)	0.002	0.056	-10000	0	-0.38	1	1
mol:LPA	0.002	0.01	-10000	0	-0.17	1	1
TRIP6/p130 Cas/FAK1/Paxillin	0.027	0.017	-10000	0	-10000	0	0
MAPKKK cascade	-0.001	0.063	-10000	0	-0.2	25	25
contractile ring contraction involved in cytokinesis	0.01	0.011	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.043	0.1	-10000	0	-0.24	61	61
GNA15	0.009	0.007	-10000	0	-10000	0	0
GNA12	0.01	0	-10000	0	-10000	0	0
GNA13	0.01	0.001	-10000	0	-10000	0	0
MAPT	0.003	0.039	-10000	0	-0.19	9	9
GNA11	0.004	0.039	-10000	0	-0.24	7	7
Rac1/GTP	0.019	0	-10000	0	-10000	0	0
MMP2	0.01	0.032	-10000	0	-0.54	1	1

×

ErbB2/ErbB3 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.006	0.002	-9999	-10000	0	0
RAS family/GTP	0.049	0.052	-9999	-0.19	5	5
NFATC4	0.008	0.036	-9999	-0.17	10	10
ERBB2IP	0.009	0.001	-9999	-10000	0	0
HSP90 (dimer)	0.01	0	-9999	-10000	0	0
mammary gland morphogenesis	0.021	0.044	-9999	-0.21	8	8
JUN	0.047	0.067	-9999	-10000	0	0
HRAS	0.011	0.001	-9999	-10000	0	0
DOCK7	0.011	0.039	-9999	-0.2	8	8
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.016	0.041	-9999	-0.22	8	8
AKT1	0.005	0.002	-9999	-10000	0	0
BAD	0.006	0.001	-9999	-10000	0	0
MAPK10	0.01	0.023	-9999	-0.12	1	1
mol:GTP	0.001	0.001	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	0.024	0.048	-9999	-0.22	8	8
RAF1	0.059	0.061	-9999	-0.23	1	1
ErbB2/ErbB3/neuregulin 2	0.01	0.036	-9999	-0.24	6	6
STAT3	0.014	0.002	-9999	-10000	0	0
cell migration	0.012	0.028	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0.001	-9999	-10000	0	0
cell proliferation	0.087	0.16	-9999	-0.44	1	1
FOS	0.04	0.22	-9999	-0.46	44	44
NRAS	0.011	0.001	-9999	-10000	0	0
mol:Ca2+	0.021	0.044	-9999	-0.21	8	8
MAPK3	0.087	0.12	-9999	-0.34	1	1
MAPK1	0.087	0.12	-9999	-0.34	1	1
JAK2	0.011	0.039	-9999	-0.2	8	8
NF2	0.008	0.004	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0.01	0.041	-9999	-0.23	8	8
NRG1	0.003	0.059	-9999	-0.44	5	5
GRB2/SOS1	0.015	0.001	-9999	-10000	0	0
MAPK8	0.012	0.058	-9999	-0.24	13	13
MAPK9	0.01	0.023	-9999	-0.12	1	1
ERBB2	0	0.003	-9999	-10000	0	0
ERBB3	0.006	0.046	-9999	-0.44	3	3
SHC1	0.011	0.001	-9999	-10000	0	0
RAC1	0.01	0	-9999	-10000	0	0
apoptosis	-0.005	0.005	-9999	-10000	0	0
STAT3 (dimer)	0.014	0.002	-9999	-10000	0	0
RNF41	0.006	0.003	-9999	-10000	0	0
FRAP1	0.003	0.001	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.004	0.026	-9999	-0.15	8	8
ErbB2/ErbB2/HSP90 (dimer)	0.008	0.003	-9999	-10000	0	0
CHRNA1	0.11	0.12	-9999	-0.26	1	1
myelination	0.006	0.034	-9999	-0.17	10	10
PPP3CB	0.011	0.037	-9999	-0.19	8	8
KRAS	0.011	0.001	-9999	-10000	0	0
RAC1-CDC42/GDP	0.02	0.037	-9999	-0.2	8	8
NRG2	0.005	0.046	-9999	-0.44	3	3
mol:GDP	0.009	0.04	-9999	-0.23	8	8
SOS1	0.01	0.001	-9999	-10000	0	0
MAP2K2	0.064	0.068	-9999	-0.24	1	1
SRC	0.01	0.001	-9999	-10000	0	0
mol:cAMP	0	0.001	-9999	-10000	0	0
PTPN11	0.01	0.038	-9999	-0.2	8	8
MAP2K1	0.072	0.12	-9999	-0.41	1	1
heart morphogenesis	0.021	0.044	-9999	-0.21	8	8
RAS family/GDP	0.036	0.042	-9999	-0.19	5	5
GRB2	0.01	0.001	-9999	-10000	0	0
PRKACA	0.007	0.004	-9999	-10000	0	0
CHRNE	0.017	0.017	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
activation of caspase activity	-0.005	0.002	-9999	-10000	0	0
nervous system development	0.021	0.044	-9999	-0.21	8	8
CDC42	0.01	0	-9999	-10000	0	0

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.01	0	-10000	0	-10000	0	0
ANTXR2	0.01	0	-10000	0	-10000	0	0
negative regulation of myeloid dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
monocyte activation	0.003	0.045	-10000	0	-0.38	4	4
MAP2K2	0.007	0	-10000	0	-10000	0	0
MAP2K1	0.003	0	-10000	0	-10000	0	0
MAP2K7	0.003	0	-10000	0	-10000	0	0
MAP2K6	0.003	0	-10000	0	-10000	0	0
CYAA	0.003	0	-10000	0	-10000	0	0
MAP2K4	0.003	0	-10000	0	-10000	0	0
IL1B	0.001	0.029	-10000	0	-0.21	5	5
Channel	0.013	0	-10000	0	-10000	0	0
NLRP1	0.003	0	-10000	0	-10000	0	0
CALM1	0.01	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	0.007	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0	0	-10000	0	-10000	0	0
MAPK3	0.003	0	-10000	0	-10000	0	0
MAPK1	0.003	0	-10000	0	-10000	0	0
PGR	-0.091	0.11	-10000	0	-0.22	121	121
PA/Cellular Receptors	0.013	0	-10000	0	-10000	0	0
apoptosis	0	0	-10000	0	-10000	0	0
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.012	0	-10000	0	-10000	0	0
macrophage activation	0.004	0	-10000	0	-10000	0	0
TNF	0.005	0.046	-10000	0	-0.44	3	3
VCAM1	0.003	0.045	-10000	0	-0.38	4	4
platelet activation	0.007	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.004	0	-10000	0	-10000	0	0
IL18	0.006	0.01	0.076	5	-10000	0	5
negative regulation of macrophage activation	0	0	-10000	0	-10000	0	0
LEF	0	0	-10000	0	-10000	0	0
CASP1	0.003	0	-10000	0	-10000	0	0
mol:cAMP	0.007	0	-10000	0	-10000	0	0
necrosis	0	0	-10000	0	-10000	0	0
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.012	0	-10000	0	-10000	0	0
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.023	0.008	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0.001	-10000	0	-10000	0	0
CRKL	0.01	0	-10000	0	-10000	0	0
STAT1 (dimer)/Cbp/p300	0.033	0.013	-10000	0	-10000	0	0
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.021	0.003	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.025	0.05	-10000	0	-0.17	1	1
CaM/Ca2+	0.024	0.007	-10000	0	-10000	0	0
RAP1A	0.01	0	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	0.022	0.013	-10000	0	-10000	0	0
AKT1	0.019	0.013	-10000	0	-10000	0	0
MAP2K1	0.018	0.014	-10000	0	-10000	0	0
MAP3K11	0.018	0.014	-10000	0	-10000	0	0
IFNGR1	0.011	0.001	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.13	0.17	-10000	0	-0.33	119	119
Rap1/GTP	0	0	-10000	0	-10000	0	0
CRKL/C3G	0.015	0	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.026	0.008	-10000	0	-10000	0	0
CEBPB	0.031	0.016	-10000	0	-10000	0	0
STAT3	0.01	0	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.019	0.089	-10000	0	-1	2	2
STAT1	0.018	0.014	-10000	0	-10000	0	0
CALM1	0.01	0	-10000	0	-10000	0	0
IFN-gamma (dimer)	0.006	0.005	-10000	0	-10000	0	0
PIK3CA	0.01	0	-10000	0	-10000	0	0
STAT1 (dimer)/PIAS1	0.023	0.014	-10000	0	-10000	0	0
CEBPB/PTGES2/Cbp/p300	0.026	0.009	-10000	0	-10000	0	0
mol:Ca2+	0.022	0.007	-10000	0	-10000	0	0
MAPK3	0.023	0.014	-10000	0	-10000	0	0
STAT1 (dimer)	-0.03	0.067	-10000	0	-0.23	1	1
MAPK1	0.023	0.014	-10000	0	-10000	0	0
JAK2	0.011	0.001	-10000	0	-10000	0	0
PIK3R1	0.01	0	-10000	0	-10000	0	0
JAK1	0.011	0.001	-10000	0	-10000	0	0
CAMK2D	0.01	0	-10000	0	-10000	0	0
DAPK1	0.029	0.013	-10000	0	-10000	0	0
SMAD7	-0.006	0.035	-10000	0	-10000	0	0
CBL/CRKL/C3G	0.027	0.012	-10000	0	-10000	0	0
PI3K	0.023	0.007	-10000	0	-10000	0	0
IFNG	0.006	0.005	-10000	0	-10000	0	0
apoptosis	0.019	0.015	-10000	0	-10000	0	0
CAMK2G	0.01	0	-10000	0	-10000	0	0
STAT3 (dimer)	0.01	0	-10000	0	-10000	0	0
CAMK2A	-0.17	0.22	-10000	0	-0.44	116	116
CAMK2B	0.002	0.052	-10000	0	-0.44	4	4
FRAP1	0.016	0.013	-10000	0	-10000	0	0
PRKCD	0.02	0.014	-10000	0	-10000	0	0
RAP1B	0.01	0	-10000	0	-10000	0	0
negative regulation of cell growth	-0.025	0.05	-10000	0	-0.17	1	1
PTPN2	0.01	0	-10000	0	-10000	0	0
EP300	0.01	0	-10000	0	-10000	0	0
IRF1	0.022	0.03	-10000	0	-0.29	2	2
STAT1 (dimer)/PIASy	0.022	0.017	0.16	2	-10000	0	2
SOCS1	0	0.1	-10000	0	-1.2	2	2
mol:GDP	0.025	0.011	-10000	0	-10000	0	0
CASP1	-0.006	0.035	-10000	0	-10000	0	0
PTGES2	0.01	0	-10000	0	-10000	0	0
IRF9	0.021	0.006	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.017	0.005	-10000	0	-10000	0	0
RAP1/GDP	0.018	0.005	-10000	0	-10000	0	0
CBL	0.018	0.014	-10000	0	-10000	0	0
MAP3K1	0.018	0.014	-10000	0	-10000	0	0
PIAS1	0.01	0	-10000	0	-10000	0	0
PIAS4	0.01	0.001	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.025	0.05	-10000	0	-0.17	1	1
PTPN11	0.017	0.015	-10000	0	-10000	0	0
CREBBP	0.01	0	-10000	0	-10000	0	0
RAPGEF1	0.01	0	-10000	0	-10000	0	0

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.006	0.082	-9999	-0.44	10	10
alphaV beta3 Integrin	-0.001	0.069	-9999	-0.31	14	14
PTK2	0.009	0.062	-9999	-0.44	4	4
positive regulation of JNK cascade	-0.005	0.036	-9999	-0.31	4	4
CDC42/GDP	0.023	0.053	-9999	-0.41	4	4
Rac1/GDP	0.023	0.053	-9999	-0.41	4	4
RAP1B	0.01	0	-9999	-10000	0	0
RAP1A	0.01	0	-9999	-10000	0	0
CTNNB1	0.01	0	-9999	-10000	0	0
CDC42/GTP	0.018	0.048	-9999	-0.38	4	4
nectin-3/I-afadin	0.01	0.038	-9999	-0.31	4	4
RAPGEF1	0.015	0.057	-9999	-0.46	4	4
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.014	0.065	-9999	-0.52	4	4
PDGFB-D/PDGFRB	-0.006	0.082	-9999	-0.44	10	10
TLN1	0.007	0.018	-9999	-10000	0	0
Rap1/GTP	-0.006	0.039	-9999	-0.33	4	4
IQGAP1	0.01	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.019	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.01	0.038	-9999	-0.31	4	4
PVR	0.01	0.001	-9999	-10000	0	0
Necl-5(dimer)	0.01	0.001	-9999	-10000	0	0
mol:GDP	0.02	0.063	-9999	-0.5	4	4
MLLT4	0.01	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
PI3K	0.017	0.052	-9999	-0.22	14	14
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.015	0.001	-9999	-10000	0	0
positive regulation of lamellipodium assembly	0.014	0.041	-9999	-0.32	4	4
PVRL1	0.01	0.001	-9999	-10000	0	0
PVRL3	0.004	0.052	-9999	-0.44	4	4
PVRL2	0.01	0	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
CDH1	-0.027	0.12	-9999	-0.44	24	24
CLDN1	0.007	0.005	-9999	-10000	0	0
JAM-A/CLDN1	0.014	0.03	-9999	-0.21	4	4
SRC	0.012	0.071	-9999	-0.57	4	4
ITGB3	-0.012	0.096	-9999	-0.44	14	14
nectin-1(dimer)/I-afadin/I-afadin	0.015	0.001	-9999	-10000	0	0
FARP2	0.018	0.062	-9999	-0.49	4	4
RAC1	0.01	0	-9999	-10000	0	0
CTNNA1	0.01	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.016	0.033	-9999	-0.26	4	4
nectin-1/I-afadin	0.015	0.001	-9999	-10000	0	0
nectin-2/I-afadin	0.015	0	-9999	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0.013	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.016	0.033	-9999	-0.26	4	4
CDC42/GTP/IQGAP1/filamentous actin	0.013	0	-9999	-10000	0	0
F11R	0.01	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.005	0.036	-9999	-0.31	4	4
alphaV/beta3 Integrin/Talin	0.008	0.053	-9999	-0.22	14	14
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.015	0	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.015	0	-9999	-10000	0	0
PIP5K1C	0.007	0.019	-9999	-0.16	4	4
VAV2	0.019	0.063	-9999	-0.5	4	4
RAP1/GDP	0.023	0.05	-9999	-0.38	4	4
ITGAV	0.01	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.016	0.032	-9999	-0.26	4	4
nectin-3(dimer)/I-afadin/I-afadin	0.01	0.038	-9999	-0.31	4	4
Rac1/GTP	0.019	0.05	-9999	-0.39	4	4
PTPRM	0.006	0.022	-9999	-0.18	4	4
E-cadherin/beta catenin/alpha catenin	0.009	0.065	-9999	-0.21	24	24
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.01	0	-9999	-10000	0	0

×

HIF-2-alpha transcription factor network

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
MMP14	0.015	0.024	-10000	0	-10000	0	0
oxygen homeostasis	0.005	0.011	-10000	0	-10000	0	0
TCEB2	0.01	0.001	-10000	0	-10000	0	0
TCEB1	0.01	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	0.042	0.05	-10000	0	-0.31	1	1
EPO	0.063	0.12	0.46	1	-0.49	1	2
FIH (dimer)	0.014	0.012	-10000	0	-10000	0	0
APEX1	0.012	0.012	-10000	0	-10000	0	0
SERPINE1	0.052	0.16	0.48	3	-0.54	11	14
FLT1	-0.015	0.11	-10000	0	-1.1	2	2
ADORA2A	0.059	0.12	0.49	3	-0.48	2	5
germ cell development	0.04	0.1	-10000	0	-0.47	2	2
SLC11A2	0.065	0.12	0.48	3	-0.49	2	5
BHLHE40	0.065	0.12	0.48	3	-0.49	2	5
HIF1AN	0.014	0.012	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	0.045	0.075	-10000	0	-0.4	1	1
ETS1	-0.004	0.042	-10000	0	-0.16	2	2
CITED2	0.014	0.02	-10000	0	-10000	0	0
KDR	-0.16	0.39	-10000	0	-0.99	53	53
PGK1	0.065	0.12	0.48	3	-0.49	2	5
SIRT1	0.01	0.001	-10000	0	-10000	0	0
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	0.084	0.13	-10000	0	-0.51	3	3
EPAS1	0.037	0.065	0.35	3	-0.36	1	4
SP1	0.016	0.014	-10000	0	-10000	0	0
ABCG2	0.063	0.13	0.48	3	-0.51	4	7
EFNA1	0.065	0.12	0.48	3	-0.49	2	5
FXN	0.059	0.12	0.49	3	-0.48	2	5
POU5F1	0.04	0.11	-10000	0	-0.49	2	2
neuron apoptosis	-0.082	0.13	0.5	3	-10000	0	3
EP300	0.01	0	-10000	0	-10000	0	0
EGLN3	0.012	0.01	-10000	0	-10000	0	0
EGLN2	0.014	0.012	-10000	0	-10000	0	0
EGLN1	0.014	0.012	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.02	0.002	-10000	0	-10000	0	0
VHL	0.01	0	-10000	0	-10000	0	0
ARNT	0.012	0.012	-10000	0	-10000	0	0
SLC2A1	0.05	0.11	0.37	1	-0.48	2	3
TWIST1	0.055	0.12	0.49	3	-0.59	2	5
ELK1	0.013	0	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.054	0.078	-10000	0	-0.4	1	1
VEGFA	0.06	0.12	-10000	0	-0.49	2	2
CREBBP	0.01	0	-10000	0	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.01	0	-9999	-10000	0	0
NFATC1	0.015	0.01	-9999	-10000	0	0
NFATC2	-0.023	0.053	-9999	-0.19	14	14
NFATC3	0.004	0.008	-9999	-10000	0	0
YWHAE	0.01	0	-9999	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.018	0.032	-9999	-10000	0	0
Exportin 1/Ran/NUP214	0.017	0.004	-9999	-10000	0	0
mol:DAG	-0.002	0.003	-9999	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	0.012	0.032	-9999	-10000	0	0
BCL2/BAX	0.014	0.001	-9999	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.002	0.011	-9999	-10000	0	0
CaM/Ca2+	-0.002	0.011	-9999	-10000	0	0
BAX	0.01	0.001	-9999	-10000	0	0
MAPK14	0.007	0.003	-9999	-10000	0	0
BAD	0.01	0	-9999	-10000	0	0
CABIN1/MEF2D	0.019	0.031	-9999	-10000	0	0
Calcineurin A alpha-beta B1/BCL2	0.01	0	-9999	-10000	0	0
FKBP8	0.01	0	-9999	-10000	0	0
activation-induced cell death of T cells	-0.019	0.031	-9999	-10000	0	0
KPNB1	0.01	0	-9999	-10000	0	0
KPNA2	0.01	0	-9999	-10000	0	0
XPO1	0.009	0.001	-9999	-10000	0	0
SFN	-0.002	0.058	-9999	-0.44	5	5
MAP3K8	0.005	0.006	-9999	-10000	0	0
NFAT4/CK1 alpha	0.004	0.015	-9999	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.093	0.14	-9999	-0.26	123	123
CABIN1	0.018	0.033	-9999	-10000	0	0
CALM1	0.003	0.008	-9999	-10000	0	0
RAN	0.009	0.001	-9999	-10000	0	0
MAP3K1	0.01	0	-9999	-10000	0	0
CAMK4	0.009	0.002	-9999	-10000	0	0
mol:Ca2+	-0.006	0.007	-9999	-10000	0	0
MAPK3	0.01	0	-9999	-10000	0	0
YWHAH	0.01	0	-9999	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.013	0.002	-9999	-10000	0	0
YWHAB	0.01	0	-9999	-10000	0	0
MAPK8	-0.003	0.059	-9999	-0.44	5	5
MAPK9	0.01	0	-9999	-10000	0	0
YWHAG	0.01	0	-9999	-10000	0	0
FKBP1A	0.01	0	-9999	-10000	0	0
NFAT1-c-4/YWHAQ	0.006	0.033	-9999	-10000	0	0
PRKCH	0.01	0	-9999	-10000	0	0
CABIN1/Cbp/p300	-0.001	0.018	-9999	-10000	0	0
CASP3	0.007	0.003	-9999	-10000	0	0
PIM1	0.01	0.001	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.002	0.006	-9999	-10000	0	0
apoptosis	0.009	0.001	-9999	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.005	0.023	-9999	-10000	0	0
PRKCB	0.01	0.001	-9999	-10000	0	0
PRKCE	0.01	0	-9999	-10000	0	0
JNK2/NFAT4	0.011	0.006	-9999	-10000	0	0
BAD/BCL-XL	0.015	0	-9999	-10000	0	0
PRKCD	0.01	0	-9999	-10000	0	0
NUP214	0.009	0.001	-9999	-10000	0	0
PRKCZ	0.005	0.006	-9999	-10000	0	0
PRKCA	0.01	0	-9999	-10000	0	0
PRKCG	0.005	0.005	-9999	-10000	0	0
PRKCQ	-0.003	0.074	-9999	-0.44	8	8
FKBP38/BCL2	0.015	0	-9999	-10000	0	0
EP300	0	0.012	-9999	-10000	0	0
PRKCB1	0	0	-9999	-10000	0	0
CSNK2A1	0.01	0	-9999	-10000	0	0
NFATc/JNK1	0.013	0.031	-9999	-10000	0	0
CaM/Ca2+/FKBP38	0.004	0.012	-9999	-10000	0	0
FKBP12/FK506	0.007	0	-9999	-10000	0	0
CSNK1A1	-0.002	0.012	-9999	-10000	0	0
CaM/Ca2+/CAMK IV	0.004	0.012	-9999	-10000	0	0
NFATc/ERK1	0.021	0.009	-9999	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	0.015	0.03	-9999	-10000	0	0
NR4A1	-0.18	0.23	-9999	-0.45	122	122
GSK3B	0.005	0.006	-9999	-10000	0	0
positive T cell selection	0.004	0.008	-9999	-10000	0	0
NFAT1/CK1 alpha	-0.02	0.045	-9999	-0.16	14	14
RCH1/ KPNB1	0.015	0	-9999	-10000	0	0
YWHAQ	0.01	0	-9999	-10000	0	0
PRKACA	0.007	0.003	-9999	-10000	0	0
AKAP5	0.01	0.001	-9999	-10000	0	0
MEF2D	0	0.012	-9999	-10000	0	0
mol:FK506	0	0	-9999	-10000	0	0
YWHAZ	0.01	0	-9999	-10000	0	0
NFATc/p38 alpha	0.018	0.013	-9999	-10000	0	0
CREBBP	0	0.012	-9999	-10000	0	0
BCL2	0.01	0	-9999	-10000	0	0

×

Canonical Wnt 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
HDAC1	0.007	0.005	-10000	0	-10000	0	0
AES	0.008	0.004	-10000	0	-10000	0	0
FBXW11	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
LRP6/FZD1	0.015	0.003	-10000	0	-10000	0	0
SMAD4	0.01	0	-10000	0	-10000	0	0
DKK2	0.008	0.026	-10000	0	-0.44	1	1
TLE1	0.008	0.004	-10000	0	-10000	0	0
MACF1	0.01	0	-10000	0	-10000	0	0
CTNNB1	0.042	0.032	-10000	0	-10000	0	0
WIF1	0.006	0.005	-10000	0	-10000	0	0
beta catenin/RanBP3	0	0.021	0.34	1	-10000	0	1
KREMEN2	0.008	0.004	-10000	0	-10000	0	0
DKK1	0.008	0.004	-10000	0	-10000	0	0
beta catenin/beta TrCP1	0.046	0.03	-10000	0	-10000	0	0
FZD1	0.01	0.002	-10000	0	-10000	0	0
AXIN2	0.011	0.019	-10000	0	-10000	0	0
AXIN1	0.01	0	-10000	0	-10000	0	0
RAN	0.01	0	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.021	0.011	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.016	0.057	-10000	0	-10000	0	0
Axin1/APC/GSK3	0.043	0.042	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin/Macf1	0.037	0.022	-10000	0	-10000	0	0
HNF1A	0.001	0.053	-10000	0	-0.44	4	4
CTBP1	0.008	0.005	-10000	0	-10000	0	0
MYC	0.014	0.028	-10000	0	-10000	0	0
RANBP3	0.01	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.016	0.017	-10000	0	-0.26	1	1
NKD1	-0.12	0.2	-10000	0	-0.44	82	82
TCF4	0.008	0.005	-10000	0	-10000	0	0
TCF3	0.008	0.005	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0.022	0.009	-10000	0	-10000	0	0
Ran/GTP	0.007	0	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	-0.013	0.058	0.42	1	-10000	0	1
LEF1	-0.028	0.12	-10000	0	-0.44	23	23
DVL1	0.012	0.005	-10000	0	-10000	0	0
CSNK2A1	0.01	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.022	0.058	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	0.015	0.007	-10000	0	-10000	0	0
LRP6	0.01	0	-10000	0	-10000	0	0
CSNK1A1	0.008	0.005	-10000	0	-10000	0	0
NLK	0.01	0.001	-10000	0	-10000	0	0
CCND1	0.008	0.077	-10000	0	-1.3	1	1
WNT1	0.008	0.004	-10000	0	-10000	0	0
GSK3A	0.01	0	-10000	0	-10000	0	0
GSK3B	0.01	0	-10000	0	-10000	0	0
FRAT1	0.01	0	-10000	0	-10000	0	0
PPP2R5D	0.074	0.1	0.23	82	-10000	0	82
APC	0.021	0.02	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.013	0.007	-10000	0	-10000	0	0
CREBBP	0.008	0.005	-10000	0	-10000	0	0

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.01	0	-9999	-10000	0	0
PTK2	0.01	0	-9999	-10000	0	0
CRKL	0.003	0.038	-9999	-0.18	11	11
GRB2/SOS1/SHC	0.02	0	-9999	-10000	0	0
HRAS	0.01	0	-9999	-10000	0	0
IRS1/Crk	0.006	0.038	-9999	-0.18	11	11
IGF-1R heterotetramer/IGF1/PTP1B	0.013	0.038	-9999	-0.24	6	6
AKT1	0.006	0.032	-9999	-0.18	6	6
BAD	0.006	0.031	-9999	-0.17	6	6
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.003	0.038	-9999	-0.18	11	11
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.007	0.039	-9999	-0.18	11	11
RAF1	0.011	0.03	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.017	0.038	-9999	-0.21	6	6
YWHAZ	0.01	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.006	0.042	-9999	-0.2	11	11
PIK3CA	0.01	0	-9999	-10000	0	0
RPS6KB1	0.006	0.032	-9999	-0.18	6	6
GNB2L1	0.01	0	-9999	-10000	0	0
positive regulation of MAPKKK cascade	0.007	0.026	-9999	-10000	0	0
PXN	0.01	0	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
cell adhesion	0	0	-9999	-10000	0	0
GRB2/SOS1	0.015	0	-9999	-10000	0	0
HRAS/GTP	0.006	0.032	-9999	-0.18	6	6
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.024	0.032	-9999	-0.19	6	6
IGF-1R heterotetramer	0.008	0.012	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	0.012	0.039	-9999	-0.18	11	11
Crk/p130 Cas/Paxillin	0.017	0.037	-9999	-0.2	6	6
IGF1R	0.008	0.012	-9999	-10000	0	0
IGF1	0	0.066	-9999	-0.45	6	6
IRS2/Crk	0.008	0.036	-9999	-0.2	6	6
PI3K	0.017	0.038	-9999	-0.17	11	11
apoptosis	-0.011	0.028	-9999	-10000	0	0
HRAS/GDP	0.007	0	-9999	-10000	0	0
PRKCD	0.007	0.048	-9999	-0.31	6	6
RAF1/14-3-3 E	0.016	0.028	-9999	-10000	0	0
BAD/14-3-3	0.012	0.03	-9999	-10000	0	0
PRKCZ	0.006	0.032	-9999	-0.18	6	6
Crk/p130 Cas/Paxillin/FAK1	0.015	0.03	-9999	-10000	0	0
PTPN1	0.01	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.007	0.051	-9999	-0.33	6	6
BCAR1	0.01	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.019	0.034	-9999	-0.21	6	6
mol:GDP	0	0	-9999	-10000	0	0
SOS1	0.01	0	-9999	-10000	0	0
IRS1/NCK2	0.007	0.038	-9999	-0.18	11	11
GRB10	0.01	0	-9999	-10000	0	0
PTPN11	0.003	0.038	-9999	-0.18	11	11
IRS1	0.001	0.041	-9999	-0.2	11	11
IRS2	0.003	0.038	-9999	-0.18	11	11
IGF-1R heterotetramer/IGF1	0.006	0.049	-9999	-0.33	6	6
GRB2	0.01	0	-9999	-10000	0	0
PDPK1	0.007	0.034	-9999	-0.19	6	6
YWHAE	0.01	0	-9999	-10000	0	0
PRKD1	0.007	0.048	-9999	-0.31	6	6
SHC1	0.01	0	-9999	-10000	0	0

×

Insulin Pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	0.014	0.028	-9999	-0.2	5	5
TC10/GTP	0.018	0.001	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	0.016	0.034	-9999	-0.24	5	5
HRAS	0.01	0	-9999	-10000	0	0
APS homodimer	0.01	0.001	-9999	-10000	0	0
GRB14	-0.021	0.11	-9999	-0.44	20	20
FOXO3	0.01	0.014	-9999	-10000	0	0
AKT1	-0.002	0.06	-9999	-0.2	23	23
INSR	0.011	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0.021	0.002	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.01	0	-9999	-10000	0	0
SORBS1	0.01	0	-9999	-10000	0	0
CRK	0.01	0	-9999	-10000	0	0
PTPN1	0.009	0.003	-9999	-10000	0	0
CAV1	0.007	0.03	-9999	-0.22	5	5
CBL/APS/CAP/Crk-II/C3G	0.029	0.002	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/NCK2	0.016	0.034	-9999	-0.24	5	5
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.013	0.029	-9999	-0.21	5	5
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.013	0.025	-9999	-10000	0	0
RPS6KB1	-0.002	0.055	-9999	-0.18	23	23
PARD6A	0.01	0	-9999	-10000	0	0
CBL	0.01	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0.008	0.001	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	0.002	0.057	-9999	-0.24	5	5
HRAS/GTP	-0.003	0.022	-9999	-0.18	4	4
Insulin Receptor	0.01	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.021	0.032	-9999	-0.22	5	5
PRKCI	0.012	0.02	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.007	0.062	-9999	-0.21	23	23
SHC1	0.01	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0.019	0.002	-9999	-10000	0	0
PI3K	0.017	0.03	-9999	-0.21	5	5
NCK2	0.01	0	-9999	-10000	0	0
RHOQ	0.01	0	-9999	-10000	0	0
mol:H2O2	0	0	-9999	-10000	0	0
HRAS/GDP	0.007	0	-9999	-10000	0	0
AKT2	-0.002	0.06	-9999	-0.2	23	23
PRKCZ	0.012	0.02	-9999	-10000	0	0
SH2B2	0.01	0.001	-9999	-10000	0	0
SHC/SHIP	0.012	0.028	-9999	-0.19	5	5
F2RL2	-0.005	0.078	-9999	-0.44	9	9
TRIP10	0.01	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	0.014	0.001	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.013	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.025	0.002	-9999	-10000	0	0
RAPGEF1	0.01	0	-9999	-10000	0	0
RASA1	0.01	0	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	0.025	0.001	-9999	-10000	0	0
TC10/GDP	0.007	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.02	0.002	-9999	-10000	0	0
INPP5D	0.007	0.029	-9999	-0.21	5	5
SOS1	0.01	0	-9999	-10000	0	0
SGK1	0.006	0.007	-9999	-10000	0	0
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.01	0	-9999	-10000	0	0
IRS1	0.002	0.059	-9999	-0.44	5	5
p62DOK/RasGAP	0.019	0.002	-9999	-10000	0	0
INS	0.001	0.002	-9999	-10000	0	0
mol:PI-3-4-P2	0.007	0.029	-9999	-0.21	5	5
GRB2	0.01	0	-9999	-10000	0	0
EIF4EBP1	-0.002	0.054	-9999	-0.18	20	20
PTPRA	0.011	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
TC10/GTP/CIP4	0.013	0	-9999	-10000	0	0
PDPK1	0.01	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.011	0.03	-9999	-0.21	5	5
Insulin Receptor/Insulin/IRS1	0.01	0.033	-9999	-0.24	5	5
Insulin Receptor/Insulin/IRS3	0.009	0.001	-9999	-10000	0	0
Par3/Par6	0.014	0.042	-9999	-0.22	9	9

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.025	0	-10000	0	-10000	0	0
HDAC3	0.01	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.001	0.011	-10000	0	-0.19	1	1
GATA1/HDAC4	0.011	0.019	-10000	0	-0.31	1	1
GATA1/HDAC5	0.012	0.004	-10000	0	-10000	0	0
GATA2/HDAC5	-0.053	0.13	-10000	0	-0.31	60	60
HDAC5/BCL6/BCoR	0.02	0.001	-10000	0	-10000	0	0
HDAC9	0.01	0	-10000	0	-10000	0	0
Glucocorticoid receptor/Hsp90/HDAC6	0.02	0	-10000	0	-10000	0	0
HDAC4/ANKRA2	0.013	0.019	-10000	0	-0.31	1	1
HDAC5/YWHAB	0.015	0	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.009	0	-10000	0	-10000	0	0
GATA2	-0.083	0.18	-10000	0	-0.44	60	60
HDAC4/RFXANK	0.013	0.019	-10000	0	-0.31	1	1
BCOR	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.01	0	-10000	0	-10000	0	0
HDAC5	0.01	0	-10000	0	-10000	0	0
GNB1/GNG2	0.015	0	-10000	0	-10000	0	0
Histones	0.017	0.012	-10000	0	-0.18	1	1
ADRBK1	0.01	0	-10000	0	-10000	0	0
HDAC4	0.008	0.026	-10000	0	-0.44	1	1
XPO1	0.01	0	-10000	0	-10000	0	0
HDAC5/ANKRA2	0.015	0	-10000	0	-10000	0	0
HDAC4/Ubc9	0.013	0.019	-10000	0	-0.31	1	1
HDAC7	0.01	0	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.015	0	-10000	0	-10000	0	0
TUBA1B	0.01	0	-10000	0	-10000	0	0
HDAC6	0.01	0	-10000	0	-10000	0	0
HDAC5/RFXANK	0.015	0	-10000	0	-10000	0	0
CAMK4	0.009	0.002	-10000	0	-10000	0	0
Tubulin/HDAC6	0.02	0	-10000	0	-10000	0	0
SUMO1	0.01	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.01	0	-10000	0	-10000	0	0
GATA1	0.007	0.004	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.01	0	-10000	0	-10000	0	0
NR3C1	0.01	0	-10000	0	-10000	0	0
SUMO1/HDAC4	0.018	0.013	-10000	0	-0.2	1	1
SRF	0.01	0	-10000	0	-10000	0	0
HDAC4/YWHAB	0.013	0.019	-10000	0	-0.31	1	1
Tubulin	0.015	0	-10000	0	-10000	0	0
HDAC4/14-3-3 E	0.013	0.019	-10000	0	-0.31	1	1
GNB1	0.01	0	-10000	0	-10000	0	0
RANGAP1	0.01	0	-10000	0	-10000	0	0
BCL6/BCoR	0.015	0.001	-10000	0	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0.019	0.016	-10000	0	-0.26	1	1
HDAC4/SRF	0.019	0.016	-10000	0	-0.26	1	1
HDAC4/ER alpha	-0.006	0.078	-10000	0	-0.31	18	18
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.017	0.012	-10000	0	-0.18	1	1
cell motility	0.02	0	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.01	0	-10000	0	-10000	0	0
HDAC7/HDAC3	0.015	0	-10000	0	-10000	0	0
BCL6	0.01	0.001	-10000	0	-10000	0	0
HDAC4/CaMK II delta B	0.008	0.026	-10000	0	-0.44	1	1
Hsp90/HDAC6	0.015	0	-10000	0	-10000	0	0
ESR1	-0.017	0.11	-10000	0	-0.44	17	17
HDAC6/HDAC11	0.015	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.019	0	-10000	0	-10000	0	0
NPC	0.006	0	-10000	0	-10000	0	0
MEF2C	0.01	0	-10000	0	-10000	0	0
RAN	0.01	0	-10000	0	-10000	0	0
HDAC4/MEF2C	0.028	0.014	-10000	0	-0.22	1	1
GNG2	0.01	0	-10000	0	-10000	0	0
NCOR2	0.01	0	-10000	0	-10000	0	0
TUBB2A	0.01	0	-10000	0	-10000	0	0
HDAC11	0.01	0	-10000	0	-10000	0	0
HSP90AA1	0.01	0	-10000	0	-10000	0	0
RANBP2	0.01	0	-10000	0	-10000	0	0
ANKRA2	0.01	0	-10000	0	-10000	0	0
RFXANK	0.01	0	-10000	0	-10000	0	0
nuclear import	-0.015	0.016	0.26	1	-10000	0	1

×

BARD1 signaling events

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
BARD1/CSTF1	0.006	0.05	-10000	0	-0.31	7	7
ATM	0.01	0	-10000	0	-10000	0	0
UBE2D3	0.01	0	-10000	0	-10000	0	0
PRKDC	0.01	0	-10000	0	-10000	0	0
ATR	0.01	0	-10000	0	-10000	0	0
UBE2L3	0.01	0	-10000	0	-10000	0	0
FANCD2	0.012	0.001	-10000	0	-10000	0	0
protein ubiquitination	0.019	0.037	-10000	0	-0.21	7	7
XRCC5	0.01	0	-10000	0	-10000	0	0
XRCC6	0.01	0	-10000	0	-10000	0	0
M/R/N Complex	0.019	0.016	-10000	0	-0.26	1	1
MRE11A	0.01	0	-10000	0	-10000	0	0
DNA-PK	0.02	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.03	0.016	-10000	0	-10000	0	0
FANCF	0.01	0	-10000	0	-10000	0	0
BRCA1	0.01	0.001	-10000	0	-10000	0	0
CCNE1	0.009	0.002	-10000	0	-10000	0	0
CDK2/Cyclin E1	0.014	0.004	-10000	0	-10000	0	0
FANCG	0.01	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.006	0.05	-10000	0	-0.31	7	7
FANCE	0.01	0	-10000	0	-10000	0	0
FANCC	0.01	0	-10000	0	-10000	0	0
NBN	0.01	0	-10000	0	-10000	0	0
FANCA	0.006	0.005	-10000	0	-10000	0	0
DNA repair	0.039	0.044	0.21	2	-10000	0	2
BRCA1/BARD1/ubiquitin	0.006	0.05	-10000	0	-0.31	7	7
BARD1/DNA-PK	0.019	0.039	-10000	0	-0.23	7	7
FANCL	0.01	0	-10000	0	-10000	0	0
mRNA polyadenylation	-0.006	0.05	0.31	7	-10000	0	7
BRCA1/BARD1/CTIP/M/R/N Complex	0.009	0.038	-10000	0	-0.21	8	8
BRCA1/BACH1/BARD1/TopBP1	0.013	0.043	-10000	0	-0.26	7	7
BRCA1/BARD1/P53	0.019	0.04	-10000	0	-0.23	7	7
BARD1/CSTF1/BRCA1	0.013	0.043	-10000	0	-0.26	7	7
BRCA1/BACH1	0.01	0.001	-10000	0	-10000	0	0
BARD1	-0.001	0.069	-10000	0	-0.44	7	7
PCNA	0.01	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	0.013	0.043	-10000	0	-0.26	7	7
BRCA1/BARD1/UbcH7	0.013	0.043	-10000	0	-0.26	7	7
BRCA1/BARD1/RAD51/PCNA	0.016	0.04	-10000	0	-0.23	7	7
BARD1/DNA-PK/P53	0.023	0.038	-10000	0	-0.22	7	7
BRCA1/BARD1/Ubiquitin	0.006	0.05	-10000	0	-0.31	7	7
BRCA1/BARD1/CTIP	0.012	0.041	-10000	0	-0.23	8	8
FA complex	0.01	0.009	-10000	0	-10000	0	0
BARD1/EWS	0.006	0.05	-10000	0	-0.31	7	7
RBBP8	0.008	0.019	-10000	0	-0.31	1	1
TP53	0.01	0	-10000	0	-10000	0	0
TOPBP1	0.01	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.018	0.039	0.23	7	-10000	0	7
BRCA1/BARD1	0.021	0.038	-10000	0	-0.22	7	7
CSTF1	0.01	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.001	0.049	-10000	0	-0.31	7	7
CDK2	0.01	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.009	0.003	-10000	0	-10000	0	0
RAD50	0.008	0.026	-10000	0	-0.44	1	1
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.006	0.05	-10000	0	-0.31	7	7
EWSR1	0.01	0	-10000	0	-10000	0	0

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.01	0	-9999	-10000	0	0
VLDLR	0.01	0	-9999	-10000	0	0
LRPAP1	0.01	0	-9999	-10000	0	0
NUDC	0.01	0	-9999	-10000	0	0
RELN/LRP8	-0.001	0.059	-9999	-0.25	15	15
CaM/Ca2+	0.007	0	-9999	-10000	0	0
KATNA1	0.01	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	0.024	0.065	-9999	-0.22	15	15
IQGAP1/CaM	0.015	0	-9999	-10000	0	0
DAB1	0.004	0.005	-9999	-10000	0	0
IQGAP1	0.01	0	-9999	-10000	0	0
PLA2G7	0.002	0.004	-9999	-10000	0	0
CALM1	0.01	0	-9999	-10000	0	0
DYNLT1	0.01	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	0.014	0.002	-9999	-10000	0	0
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.01	0	-9999	-10000	0	0
CDK5R1	0.01	0.001	-9999	-10000	0	0
LIS1/Poliovirus Protein 3A	0.007	0	-9999	-10000	0	0
CDK5R2	0.006	0.005	-9999	-10000	0	0
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.004	0.059	-9999	-0.25	15	15
YWHAE	0.01	0	-9999	-10000	0	0
NDEL1/14-3-3 E	0.024	0.055	-9999	-10000	0	0
MAP1B	0.003	0	-9999	-10000	0	0
RAC1	0.009	0	-9999	-10000	0	0
p35/CDK5	0.028	0.06	-9999	-0.2	13	13
RELN	-0.017	0.099	-9999	-0.44	15	15
PAFAH/LIS1	0.003	0.005	-9999	-10000	0	0
LIS1/CLIP170	0.014	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	0.002	0.035	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.002	0.049	-9999	-0.21	14	14
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	0.021	0.056	-9999	-0.19	11	11
LIS1/IQGAP1	0.014	0	-9999	-10000	0	0
RHOA	0.009	0	-9999	-10000	0	0
PAFAH1B1	0.009	0	-9999	-10000	0	0
PAFAH1B3	0.01	0.001	-9999	-10000	0	0
PAFAH1B2	0.008	0.026	-9999	-0.44	1	1
MAP1B/LIS1/Dynein heavy chain	0.014	0.002	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	0.035	0.053	-9999	-10000	0	0
LRP8	0.01	0.001	-9999	-10000	0	0
NDEL1/Katanin 60	0.024	0.055	-9999	-10000	0	0
P39/CDK5	0.02	0.057	-9999	-0.2	11	11
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.014	0	-9999	-10000	0	0
CDK5	0.025	0.063	-9999	-0.21	13	13
PPP2R5D	0.01	0.001	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.012	0	-9999	-10000	0	0
CSNK2A1	0.01	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	0.001	0.051	-9999	-0.22	14	14
RELN/VLDLR	0.003	0.054	-9999	-0.22	15	15
CDC42	0.009	0	-9999	-10000	0	0

×

FAS signaling pathway (CD95)

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
SPTAN1	0.001	0.003	-9999	-10000	0	0
RFC1	0.001	0.003	-9999	-10000	0	0
PRKDC	0.001	0.003	-9999	-10000	0	0
RIPK1	0.01	0.003	-9999	-10000	0	0
CASP7	0.004	0.024	-9999	-10000	0	0
FASLG/FAS/FADD/FAF1	0.002	0.018	-9999	-10000	0	0
MAP2K4	0.002	0.086	-9999	-0.26	25	25
mol:ceramide	0.006	0.053	-9999	-10000	0	0
GSN	0.001	0.003	-9999	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 8	0.005	0.03	-9999	-10000	0	0
FAS	0.008	0.008	-9999	-10000	0	0
BID	0	0.003	-9999	-10000	0	0
MAP3K1	0.004	0.051	-9999	-10000	0	0
MAP3K7	0.009	0.005	-9999	-10000	0	0
RB1	0.001	0.003	-9999	-10000	0	0
CFLAR	0.01	0.003	-9999	-10000	0	0
HGF/MET	0.003	0.06	-9999	-0.24	17	17
ARHGDIB	0.001	0.003	-9999	-10000	0	0
FADD	0.008	0.008	-9999	-10000	0	0
actin filament polymerization	-0.001	0.003	-9999	-10000	0	0
NFKB1	-0.006	0.064	-9999	-10000	0	0
MAPK8	-0.016	0.14	-9999	-0.44	29	29
DFFA	0.001	0.003	-9999	-10000	0	0
DNA fragmentation during apoptosis	0.001	0.003	-9999	-10000	0	0
FAS/FADD/MET	0.015	0.013	-9999	-10000	0	0
CFLAR/RIP1	0.015	0.007	-9999	-10000	0	0
FAIM3	0.009	0.003	-9999	-10000	0	0
FAF1	0.008	0.01	-9999	-10000	0	0
PARP1	0.001	0.003	-9999	-10000	0	0
DFFB	0.001	0.003	-9999	-10000	0	0
CHUK	-0.004	0.058	-9999	-10000	0	0
FASLG	0.007	0.01	-9999	-10000	0	0
FAS/FADD	0.012	0.012	-9999	-10000	0	0
HGF	-0.017	0.11	-9999	-0.44	17	17
LMNA	0.002	0.002	-9999	-10000	0	0
CASP6	0.001	0.003	-9999	-10000	0	0
CASP10	0.008	0.008	-9999	-10000	0	0
CASP3	-0.001	0.003	-9999	-10000	0	0
PTPN13	0.01	0	-9999	-10000	0	0
CASP8	-0.004	0.003	-9999	-10000	0	0
IL6	-0.089	0.36	-9999	-1.1	29	29
MET	0.009	0.003	-9999	-10000	0	0
ICAD/CAD	0.002	0.002	-9999	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 10	0.006	0.053	-9999	-10000	0	0
activation of caspase activity by cytochrome c	0	0.003	-9999	-10000	0	0
PAK2	0.001	0.004	-9999	-10000	0	0
BCL2	0.01	0.001	-9999	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.005	0.027	-9999	-0.26	3	3
SNTA1	0.005	0.046	-9999	-0.44	3	3
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.005	0.027	-9999	-0.26	3	3
MAPK12	0.007	0.014	-9999	-0.23	1	1
CCND1	0.007	0.024	-9999	-0.4	1	1
p38 gamma/SNTA1	0.012	0.027	-9999	-0.21	4	4
MAP2K3	0.01	0	-9999	-10000	0	0
PKN1	0.01	0	-9999	-10000	0	0
G2/M transition checkpoint	0.007	0.014	-9999	-0.23	1	1
MAP2K6	0.008	0	-9999	-10000	0	0
MAPT	-0.002	0.056	-9999	-0.26	13	13
MAPK13	0.006	0.032	-9999	-0.31	3	3
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.008	0	-9999	-10000	0	0

×

IL2 signaling events mediated by PI3K

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
BCL2L1	0.032	0.015	-10000	0	-10000	0	0
UGCG	0.013	0.049	-10000	0	-0.57	2	2
AKT1/mTOR/p70S6K/Hsp90/TERT	0.062	0.035	0.21	3	-10000	0	3
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.015	0.049	-10000	0	-0.57	2	2
mol:DAG	0.004	0.002	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0.044	0.021	-10000	0	-10000	0	0
FRAP1	0.062	0.034	0.23	1	-10000	0	1
FOXO3	0.058	0.031	0.22	1	-10000	0	1
AKT1	0.057	0.031	0.22	2	-10000	0	2
GAB2	0.011	0.001	-10000	0	-10000	0	0
SMPD1	0.017	0.008	-10000	0	-10000	0	0
SGMS1	0.017	0.008	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
mol:GDP	0.009	0.002	-10000	0	-10000	0	0
CALM1	0.01	0	-10000	0	-10000	0	0
cell proliferation	0.035	0.032	-10000	0	-0.28	2	2
EIF3A	0.01	0	-10000	0	-10000	0	0
PI3K	0.018	0.002	-10000	0	-10000	0	0
RPS6KB1	0.034	0.031	-10000	0	-10000	0	0
mol:sphingomyelin	0.004	0.002	-10000	0	-10000	0	0
natural killer cell activation	0.001	0.001	-10000	0	-10000	0	0
JAK3	0.009	0.005	-10000	0	-10000	0	0
PIK3R1	0.012	0.001	-10000	0	-10000	0	0
JAK1	0.011	0.001	-10000	0	-10000	0	0
NFKB1	0.01	0	-10000	0	-10000	0	0
MYC	0.059	0.034	-10000	0	-10000	0	0
MYB	0.058	0.068	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.047	0.024	0.2	1	-10000	0	1
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.042	0.026	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.047	0.024	0.2	1	-10000	0	1
Rac1/GDP	0.015	0.002	-10000	0	-10000	0	0
T cell proliferation	0.05	0.026	0.19	1	-10000	0	1
SHC1	0.011	0.001	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.013	0.019	0.048	67	-10000	0	67
PRKCZ	0.049	0.024	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.063	0.028	0.21	1	-10000	0	1
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.019	0.012	-10000	0	-10000	0	0
HSP90AA1	0.01	0	-10000	0	-10000	0	0
RELA	0.01	0	-10000	0	-10000	0	0
IL2RA	0.009	0.003	-10000	0	-10000	0	0
IL2RB	0.01	0.004	-10000	0	-10000	0	0
TERT	0.002	0.004	-10000	0	-10000	0	0
E2F1	0.019	0.022	-10000	0	-10000	0	0
SOS1	0.011	0.001	-10000	0	-10000	0	0
RPS6	0.01	0	-10000	0	-10000	0	0
mol:cAMP	-0.007	0.011	-10000	0	-0.027	67	67
PTPN11	0.011	0.001	-10000	0	-10000	0	0
IL2RG	0.011	0.002	-10000	0	-10000	0	0
actin cytoskeleton organization	0.05	0.026	0.19	1	-10000	0	1
GRB2	0.011	0.001	-10000	0	-10000	0	0
IL2	0.005	0.005	-10000	0	-10000	0	0
PIK3CA	0.012	0.001	-10000	0	-10000	0	0
Rac1/GTP	0.026	0.008	-10000	0	-10000	0	0
LCK	0.011	0.002	-10000	0	-10000	0	0
BCL2	0.06	0.032	-10000	0	-10000	0	0

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	0.01	0.024	-10000	0	-0.17	5	5
DAPP1	0.026	0.039	-10000	0	-0.55	1	1
Src family/SYK family/BLNK-LAT/BTK-ITK	0.036	0.054	-10000	0	-0.52	1	1
mol:DAG	0.028	0.049	0.14	6	-0.17	8	14
HRAS	0.01	0.003	-10000	0	-10000	0	0
RAP1A	0.01	0.003	-10000	0	-10000	0	0
ARF5/GDP	0.023	0.026	-10000	0	-0.25	2	2
PLCG2	-0.015	0.1	-10000	0	-0.44	16	16
PLCG1	0.01	0	-10000	0	-10000	0	0
ARF5	0.01	0	-10000	0	-10000	0	0
mol:GTP	0.002	0.024	-10000	0	-0.18	5	5
ARF1/GTP	0.006	0.026	-10000	0	-0.19	5	5
RHOA	0.01	0	-10000	0	-10000	0	0
YES1	0.01	0	-10000	0	-10000	0	0
RAP1A/GTP	0.007	0.025	-10000	0	-0.18	5	5
ADAP1	0.004	0.023	-10000	0	-0.17	5	5
ARAP3	0.002	0.025	-10000	0	-0.18	5	5
INPPL1	0.01	0	-10000	0	-10000	0	0
PREX1	0.007	0.037	-10000	0	-0.44	2	2
ARHGEF6	0.01	0	-10000	0	-10000	0	0
ARHGEF7	0.01	0	-10000	0	-10000	0	0
ARF1	0.01	0	-10000	0	-10000	0	0
NRAS	0.01	0.003	-10000	0	-10000	0	0
FYN	0.01	0	-10000	0	-10000	0	0
ARF6	0.01	0	-10000	0	-10000	0	0
FGR	0.008	0.026	-10000	0	-0.44	1	1
mol:Ca2+	0.018	0.026	0.1	2	-0.12	1	3
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.01	0	-10000	0	-10000	0	0
ZAP70	0.009	0.003	-10000	0	-10000	0	0
mol:IP3	0.022	0.035	0.12	3	-0.18	1	4
LYN	0.01	0	-10000	0	-10000	0	0
ARF1/GDP	0.023	0.026	-10000	0	-0.25	2	2
RhoA/GDP	0.021	0.028	-10000	0	-0.23	1	1
PDK1/Src/Hsp90	0.02	0.001	-10000	0	-10000	0	0
BLNK	-0.006	0.082	-10000	0	-0.44	10	10
actin cytoskeleton reorganization	0.021	0.038	-10000	0	-0.32	2	2
SRC	0.01	0.001	-10000	0	-10000	0	0
PLEKHA2	0.008	0.001	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
PTEN	0.009	0.002	-10000	0	-10000	0	0
HSP90AA1	0.01	0	-10000	0	-10000	0	0
ARF6/GTP	0.01	0.024	-10000	0	-10000	0	0
RhoA/GTP	0.008	0.024	-10000	0	-0.17	5	5
Src family/SYK family/BLNK-LAT	0.01	0.04	-10000	0	-0.33	1	1
BLK	0.008	0.004	-10000	0	-10000	0	0
PDPK1	0.01	0	-10000	0	-10000	0	0
CYTH1	0.004	0.023	-10000	0	-0.17	5	5
HCK	0.007	0.026	-10000	0	-0.44	1	1
CYTH3	0.004	0.023	-10000	0	-0.17	5	5
CYTH2	0.004	0.023	-10000	0	-0.17	5	5
KRAS	0.01	0.003	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.014	0.014	-10000	0	-10000	0	0
SGK1	0.014	0.015	-10000	0	-10000	0	0
INPP5D	0.009	0.002	-10000	0	-10000	0	0
mol:GDP	0.017	0.027	-10000	0	-0.27	2	2
SOS1	0.01	0	-10000	0	-10000	0	0
SYK	0.008	0.026	-10000	0	-0.44	1	1
ARF6/GDP	0.017	0.028	-10000	0	-0.23	1	1
mol:PI-3-4-5-P3	0.002	0.024	-10000	0	-0.18	5	5
ARAP3/RAP1A/GTP	0.007	0.025	-10000	0	-0.18	5	5
VAV1	0.006	0.027	-10000	0	-0.44	1	1
mol:PI-3-4-P2	0.009	0.002	-10000	0	-10000	0	0
RAS family/GTP/PI3K Class I	0.014	0.026	-10000	0	-0.18	5	5
PLEKHA1	0.008	0.001	-10000	0	-10000	0	0
Rac1/GDP	0.023	0.026	-10000	0	-0.25	2	2
LAT	0.009	0.003	-10000	0	-10000	0	0
Rac1/GTP	0.011	0.03	-10000	0	-0.31	2	2
ITK	0.003	0.023	-10000	0	-0.17	5	5
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.032	0.062	0.17	6	-0.23	8	14
LCK	0.01	0.001	-10000	0	-10000	0	0
BTK	0.002	0.023	-10000	0	-0.17	5	5

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.013	0.051	-9999	-0.6	2	2
VEGFR1 homodimer/NRP1	0.006	0.05	-9999	-0.6	2	2
mol:DAG	0.01	0.046	-9999	-0.55	2	2
VEGFR1 homodimer/NRP1/VEGFR 121	0.012	0.047	-9999	-0.55	2	2
CaM/Ca2+	0.015	0.044	-9999	-0.52	2	2
HIF1A	0.012	0.028	-9999	-0.32	2	2
GAB1	0.01	0	-9999	-10000	0	0
AKT1	0.016	0.043	-9999	-0.49	2	2
PLCG1	0.01	0.047	-9999	-0.55	2	2
NOS3	0.008	0.07	-9999	-0.32	12	12
CBL	0.01	0	-9999	-10000	0	0
mol:NO	0.009	0.068	-9999	-0.31	12	12
FLT1	0.009	0.058	-9999	-0.68	2	2
PGF	0.01	0.001	-9999	-10000	0	0
VEGFR1 homodimer/NRP2/VEGFR121	0.017	0.05	-9999	-0.44	3	3
CALM1	0.01	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
eNOS/Hsp90	0.014	0.067	-9999	-0.46	2	2
endothelial cell proliferation	0.014	0.047	-9999	-0.54	2	2
mol:Ca2+	0.01	0.046	-9999	-0.54	2	2
MAPK3	0.009	0.041	-9999	-0.48	2	2
MAPK1	0.009	0.041	-9999	-0.48	2	2
PIK3R1	0.01	0	-9999	-10000	0	0
PLGF homodimer	0.01	0.001	-9999	-10000	0	0
PRKACA	0.01	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	0.01	0.001	-9999	-10000	0	0
VEGFA homodimer	0.01	0.001	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0.013	0.051	-9999	-0.6	2	2
platelet activating factor biosynthetic process	0.011	0.041	-9999	-0.47	2	2
PI3K	0.024	0.046	-9999	-0.52	2	2
PRKCA	0.009	0.043	-9999	-0.51	2	2
PRKCB	0.009	0.043	-9999	-0.51	2	2
VEGFR1 homodimer/PLGF homodimer	0.013	0.051	-9999	-0.6	2	2
VEGFA	0.01	0.001	-9999	-10000	0	0
VEGFB	0.01	0	-9999	-10000	0	0
mol:IP3	0.01	0.046	-9999	-0.55	2	2
RASA1	0.01	0.047	-9999	-0.55	2	2
NRP2	0.008	0.026	-9999	-0.44	1	1
VEGFR1 homodimer	0.009	0.057	-9999	-0.68	2	2
VEGFB homodimer	0.01	0	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.014	0.067	-9999	-0.46	2	2
PTPN11	0.01	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.023	0.045	-9999	-0.51	2	2
mol:L-citrulline	0.009	0.068	-9999	-0.31	12	12
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.024	0.046	-9999	-0.52	2	2
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.019	0.048	-9999	-0.55	2	2
CD2AP	0.01	0	-9999	-10000	0	0
PI3K/GAB1	0.027	0.044	-9999	-0.5	2	2
PDPK1	0.014	0.043	-9999	-0.49	2	2
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.019	0.048	-9999	-0.55	2	2
mol:NADP	0.009	0.068	-9999	-0.31	12	12
HSP90AA1	0.01	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.023	0.045	-9999	-0.52	2	2
VEGFR1 homodimer/NRP2	0.012	0.053	-9999	-0.48	3	3

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.016	0.015	-9999	-10000	0	0
STMN1	0.006	0.006	-9999	-10000	0	0
Aurora B/RasGAP/Survivin	0.013	0.014	-9999	-10000	0	0
Chromosomal passenger complex/Cul3 protein complex	0.007	0.042	-9999	-0.18	10	10
BIRC5	0.008	0.006	-9999	-10000	0	0
DES	-0.21	0.25	-9999	-0.5	122	122
Aurora C/Aurora B/INCENP	0.013	0.014	-9999	-10000	0	0
Aurora B/TACC1	0.009	0.009	-9999	-10000	0	0
Aurora B/PP2A	0.01	0.01	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CBX5	0.004	0.004	-9999	-10000	0	0
mitotic metaphase/anaphase transition	0	0.001	-9999	-10000	0	0
NDC80	0.006	0.006	-9999	-10000	0	0
Cul3 protein complex	0	0.072	-9999	-0.26	21	21
KIF2C	0.014	0.016	-9999	-10000	0	0
PEBP1	0.013	0.003	-9999	-10000	0	0
KIF20A	0.006	0.004	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	0.01	0.01	-9999	-10000	0	0
SEPT1	0.01	0.001	-9999	-10000	0	0
SMC2	0.01	0	-9999	-10000	0	0
SMC4	0.01	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	0.004	0.008	-9999	-10000	0	0
PSMA3	0.01	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0	0	-9999	-10000	0	0
H3F3B	0.005	0.005	-9999	-10000	0	0
AURKB	0.008	0.009	-9999	-10000	0	0
AURKC	0.01	0.001	-9999	-10000	0	0
CDCA8	0.012	0.005	-9999	-10000	0	0
cytokinesis	0.006	0.011	-9999	-10000	0	0
Aurora B/Septin1	0.017	0.016	-9999	-10000	0	0
AURKA	0.009	0.002	-9999	-10000	0	0
INCENP	0.014	0.004	-9999	-10000	0	0
KLHL13	-0.021	0.11	-9999	-0.44	20	20
BUB1	0.006	0.005	-9999	-10000	0	0
hSgo1/Aurora B/Survivin	0.013	0.014	-9999	-10000	0	0
EVI5	0.012	0.001	-9999	-10000	0	0
RhoA/GTP	0.022	0.021	-9999	-10000	0	0
SGOL1	0.009	0.003	-9999	-10000	0	0
CENPA	0.015	0.019	-9999	-10000	0	0
NCAPG	0.007	0.004	-9999	-10000	0	0
Aurora B/HC8 Proteasome	0.01	0.01	-9999	-10000	0	0
NCAPD2	0.01	0	-9999	-10000	0	0
Aurora B/PP1-gamma	0.01	0.01	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
NCAPH	0.008	0.004	-9999	-10000	0	0
NPM1	0.004	0.008	-9999	-10000	0	0
RASA1	0.01	0	-9999	-10000	0	0
KLHL9	0.008	0.026	-9999	-0.44	1	1
mitotic prometaphase	0.003	0.003	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.01	0.01	-9999	-10000	0	0
PPP1CC	0.01	0	-9999	-10000	0	0
Centraspindlin	0.027	0.026	-9999	-10000	0	0
RhoA/GDP	0.007	0	-9999	-10000	0	0
NSUN2	0.004	0.008	-9999	-10000	0	0
MYLK	-0.004	0.048	-9999	-0.26	10	10
KIF23	0.012	0.002	-9999	-10000	0	0
VIM	0.006	0.006	-9999	-10000	0	0
RACGAP1	0.012	0.002	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
NCL	0.004	0.008	-9999	-10000	0	0
Chromosomal passenger complex	0.022	0.026	-9999	-10000	0	0
Chromosomal passenger complex/EVI5	0.032	0.037	-9999	-10000	0	0
TACC1	0.01	0	-9999	-10000	0	0
PPP2R5D	0.01	0.001	-9999	-10000	0	0
CUL3	0.01	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.01	0	-9999	-10000	0	0
HDAC2	0.01	0	-9999	-10000	0	0
GNB1/GNG2	0.019	0.023	-9999	-0.26	2	2
forebrain development	0.018	0.057	-9999	-0.36	4	4
GNAO1	-0.029	0.13	-9999	-0.44	25	25
SMO/beta Arrestin2	0.014	0.027	-9999	-0.31	2	2
SMO	0.008	0.037	-9999	-0.44	2	2
ARRB2	0.01	0.001	-9999	-10000	0	0
GLI3/SPOP	0.024	0.018	-9999	-10000	0	0
mol:GTP	0	0.001	-9999	-10000	0	0
GSK3B	0.01	0	-9999	-10000	0	0
GNAI2	0.01	0.001	-9999	-10000	0	0
SIN3/HDAC complex	0.024	0.002	-9999	-10000	0	0
GNAI1	0.007	0.037	-9999	-0.44	2	2
XPO1	0.012	0.004	-9999	-10000	0	0
GLI1/Su(fu)	0.022	0.047	-9999	-10000	0	0
SAP30	0.01	0.001	-9999	-10000	0	0
mol:GDP	0.008	0.037	-9999	-0.44	2	2
MIM/GLI2A	0.014	0.031	-9999	-0.44	1	1
IFT88	0.01	0	-9999	-10000	0	0
GNAI3	0.01	0.001	-9999	-10000	0	0
GLI2	0.01	0.038	-9999	-10000	0	0
GLI3	0.019	0.019	-9999	-0.23	1	1
CSNK1D	0.01	0	-9999	-10000	0	0
CSNK1E	0.01	0	-9999	-10000	0	0
SAP18	0.01	0	-9999	-10000	0	0
embryonic digit morphogenesis	0.01	0	-9999	-10000	0	0
GNG2	0.01	0	-9999	-10000	0	0
Gi family/GTP	-0.004	0.068	-9999	-0.21	29	29
SIN3B	0.01	0	-9999	-10000	0	0
SIN3A	0.01	0	-9999	-10000	0	0
GLI3/Su(fu)	0.027	0.012	-9999	-10000	0	0
GLI2/Su(fu)	0.018	0.036	-9999	-10000	0	0
FOXA2	0.006	0.041	-9999	-0.66	1	1
neural tube patterning	0.018	0.057	-9999	-0.36	4	4
SPOP	0.01	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.018	0.014	-9999	-10000	0	0
GNB1	0.01	0	-9999	-10000	0	0
CSNK1G2	0.01	0	-9999	-10000	0	0
CSNK1G3	0.01	0	-9999	-10000	0	0
MTSS1	0.014	0.031	-9999	-0.44	1	1
embryonic limb morphogenesis	0.018	0.057	-9999	-0.36	4	4
SUFU	0.013	0.016	-9999	-10000	0	0
LGALS3	0.008	0.026	-9999	-0.44	1	1
catabolic process	0.027	0.031	-9999	-10000	0	0
GLI3A/CBP	0.011	0.04	-9999	-0.32	4	4
KIF3A	0.01	0	-9999	-10000	0	0
GLI1	0.018	0.058	-9999	-0.37	4	4
RAB23	0.01	0	-9999	-10000	0	0
CSNK1A1	0.01	0	-9999	-10000	0	0
IFT172	0.01	0	-9999	-10000	0	0
RBBP7	0.01	0	-9999	-10000	0	0
Su(fu)/Galectin3	0.017	0.019	-9999	-0.23	1	1
GNAZ	0.01	0.001	-9999	-10000	0	0
RBBP4	0.01	0	-9999	-10000	0	0
CSNK1G1	0.01	0	-9999	-10000	0	0
PIAS1	0.01	0	-9999	-10000	0	0
PRKACA	0.01	0	-9999	-10000	0	0
GLI2/SPOP	0.015	0.036	-9999	-10000	0	0
STK36	0.012	0.003	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	0	0.06	-9999	-10000	0	0
PTCH1	0.021	0.054	-9999	-10000	0	0
MIM/GLI1	0.028	0.064	-9999	-0.35	4	4
CREBBP	0.011	0.04	-9999	-0.32	4	4
Su(fu)/SIN3/HDAC complex	0.02	0.005	-9999	-10000	0	0

×

mTOR signaling 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.01	0	-10000	0	-10000	0	0
mol:PIP3	0.001	0.035	-10000	0	-0.26	5	5
FRAP1	0.005	0.006	-10000	0	-10000	0	0
AKT1	0.004	0.029	-10000	0	-0.22	5	5
INSR	0.01	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.007	0.001	-10000	0	-10000	0	0
mol:GTP	0.013	0.025	-10000	0	-0.17	5	5
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.001	0.008	-10000	0	-10000	0	0
TSC2	0.01	0	-10000	0	-10000	0	0
RHEB/GDP	0.01	0.021	-10000	0	-0.15	5	5
TSC1	0.01	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.005	0.042	-10000	0	-0.31	5	5
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.013	0.011	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.01	0	-10000	0	-10000	0	0
RPS6KB1	0.009	0.015	-10000	0	-10000	0	0
MAP3K5	0.004	0	-10000	0	-10000	0	0
PIK3R1	0.01	0	-10000	0	-10000	0	0
apoptosis	0.004	0	-10000	0	-10000	0	0
mol:LY294002	0	0	-10000	0	-0.001	5	5
EIF4B	0.009	0.014	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.017	0.014	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	0.009	0.004	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.011	0.039	-10000	0	-0.28	5	5
mTOR/RHEB/GTP/Raptor/GBL	0.008	0.009	-10000	0	-10000	0	0
FKBP1A	0.01	0	-10000	0	-10000	0	0
RHEB/GTP	0.015	0.021	-10000	0	-0.15	5	5
mol:Amino Acids	0	0	-10000	0	-0.001	5	5
FKBP12/Rapamycin	0.007	0	-10000	0	-10000	0	0
PDPK1	0.002	0.032	-10000	0	-0.24	5	5
EIF4E	0.01	0	-10000	0	-10000	0	0
ASK1/PP5C	0.015	0.004	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.008	0	-10000	0	-10000	0	0
TSC1/TSC2	0.015	0.026	-10000	0	-0.18	5	5
tumor necrosis factor receptor activity	0	0	0.001	5	-10000	0	5
RPS6	0.01	0	-10000	0	-10000	0	0
PPP5C	0.01	0	-10000	0	-10000	0	0
EIF4G1	0.01	0	-10000	0	-10000	0	0
IRS1	-0.002	0.044	-10000	0	-0.33	5	5
INS	0	0.002	-10000	0	-10000	0	0
PTEN	0.01	0	-10000	0	-10000	0	0
PDK2	0.002	0.032	-10000	0	-0.24	5	5
EIF4EBP1	0.01	0.001	-10000	0	-10000	0	0
PIK3CA	0.01	0	-10000	0	-10000	0	0
PPP2R5D	0.007	0.006	-10000	0	-10000	0	0
peptide biosynthetic process	0.008	0.001	-10000	0	-10000	0	0
RHEB	0.01	0	-10000	0	-10000	0	0
EIF4A1	0.01	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	-10000	0	-10000	0	0
EEF2	0.008	0.001	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.014	0	-10000	0	-10000	0	0

×

Ephrin B reverse signaling

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
EFNB2	0.01	0	-10000	0	-10000	0	0
EPHB2	0.01	0.001	-10000	0	-10000	0	0
EFNB1	0.005	0.019	-10000	0	-0.31	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.016	0.026	-10000	0	-0.2	2	2
Ephrin B2/EPHB1-2	0.016	0.025	-10000	0	-0.23	3	3
neuron projection morphogenesis	0.01	0.022	-10000	0	-0.19	2	2
Ephrin B1/EPHB1-2/Tiam1	0.014	0.026	-10000	0	-0.18	4	4
DNM1	0.005	0.027	-10000	0	-0.44	1	1
cell-cell signaling	0	0	-10000	0	-10000	0	0
MAP2K4	0.01	0.003	-10000	0	-10000	0	0
YES1	0.005	0.005	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK2	0.014	0.026	-10000	0	-0.18	4	4
PI3K	0.02	0.003	-10000	0	-10000	0	0
mol:GDP	0.013	0.026	-10000	0	-0.18	4	4
ITGA2B	0.009	0.003	-10000	0	-10000	0	0
endothelial cell proliferation	0.013	0	-10000	0	-10000	0	0
FYN	0.005	0.005	-10000	0	-10000	0	0
MAP3K7	0.004	0.004	-10000	0	-10000	0	0
FGR	0.004	0.011	-10000	0	-10000	0	0
TIAM1	0.01	0	-10000	0	-10000	0	0
PIK3R1	0.01	0	-10000	0	-10000	0	0
RGS3	0.01	0	-10000	0	-10000	0	0
cell adhesion	0.008	0.046	-10000	0	-0.2	12	12
LYN	0.005	0.005	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/Src Family Kinases	0.003	0.004	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2	0.003	0.004	-10000	0	-10000	0	0
SRC	0.005	0.005	-10000	0	-10000	0	0
ITGB3	-0.012	0.096	-10000	0	-0.44	14	14
EPHB1	0.005	0.045	-10000	0	-0.44	3	3
EPHB4	0.01	0	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.013	0	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.003	0.069	-10000	0	-0.31	14	14
BLK	0.005	0.005	-10000	0	-10000	0	0
HCK	0.004	0.011	-10000	0	-10000	0	0
regulation of stress fiber formation	-0.013	0.026	0.18	4	-10000	0	4
MAPK8	0.007	0.028	-10000	0	-0.2	5	5
Ephrin B1/EPHB1-2/RGS3	0.014	0.026	-10000	0	-0.18	4	4
endothelial cell migration	0.004	0.004	-10000	0	-10000	0	0
NCK2	0.01	0	-10000	0	-10000	0	0
PTPN13	0.007	0.003	-10000	0	-10000	0	0
regulation of focal adhesion formation	-0.013	0.026	0.18	4	-10000	0	4
chemotaxis	-0.013	0.026	0.18	4	-10000	0	4
PIK3CA	0.01	0	-10000	0	-10000	0	0
Rac1/GTP	0.013	0.024	-10000	0	-0.2	2	2
angiogenesis	0.003	0.003	-10000	0	-10000	0	0
LCK	0.005	0.005	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	0.022	0.031	-9999	-0.27	3	3
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.022	0.031	-9999	-0.27	3	3
SUMO1	0.01	0	-9999	-10000	0	0
ZFPM1	0.01	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.009	0	-9999	-10000	0	0
FKBP3	0.01	0	-9999	-10000	0	0
Histones	0.028	0.017	-9999	-10000	0	0
YY1/LSF	0.016	0	-9999	-10000	0	0
SMG5	0.01	0	-9999	-10000	0	0
RAN	0.01	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	0.012	0.024	-9999	-0.22	3	3
I kappa B alpha/HDAC1	0.015	0.018	-9999	-10000	0	0
SAP18	0.01	0	-9999	-10000	0	0
RELA	0.016	0.025	-9999	-0.21	3	3
HDAC1/Smad7	0.02	0	-9999	-10000	0	0
RANGAP1	0.01	0	-9999	-10000	0	0
HDAC3/TR2	0.015	0.018	-9999	-0.15	3	3
NuRD/MBD3 Complex	0.02	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.02	0.023	-9999	-0.19	3	3
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.083	0.18	-9999	-0.44	60	60
GATA1	0.007	0.004	-9999	-10000	0	0
Mad/Max	0.015	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.023	0.006	-9999	-10000	0	0
RBBP7	0.01	0	-9999	-10000	0	0
NPC	0.006	0	-9999	-10000	0	0
RBBP4	0.01	0	-9999	-10000	0	0
MAX	0.01	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.01	0	-9999	-10000	0	0
NFKBIA	0.011	0.019	-9999	-0.17	3	3
KAT2B	0.01	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.018	0.002	-9999	-10000	0	0
SIN3 complex	0.025	0.002	-9999	-10000	0	0
SMURF1	0.01	0	-9999	-10000	0	0
CHD3	0.01	0	-9999	-10000	0	0
SAP30	0.01	0.001	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.01	0	-9999	-10000	0	0
YY1/HDAC3	0.017	0.016	-9999	-10000	0	0
YY1/HDAC2	0.016	0	-9999	-10000	0	0
YY1/HDAC1	0.016	0	-9999	-10000	0	0
NuRD/MBD2 Complex (MeCP1)	0.02	0	-9999	-10000	0	0
PPARG	0.013	0.029	-9999	-0.27	3	3
HDAC8/hEST1B	0.02	0	-9999	-10000	0	0
UBE2I	0.01	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.01	0	-9999	-10000	0	0
TNFRSF1A	0.01	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.015	0.018	-9999	-10000	0	0
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.02	0	-9999	-10000	0	0
CREBBP	0.01	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.022	0	-9999	-10000	0	0
HDAC1	0.01	0	-9999	-10000	0	0
HDAC3	0.011	0.019	-9999	-0.17	3	3
HDAC2	0.01	0	-9999	-10000	0	0
YY1	0.013	0	-9999	-10000	0	0
HDAC8	0.01	0	-9999	-10000	0	0
SMAD7	0.01	0	-9999	-10000	0	0
NCOR2	0.01	0	-9999	-10000	0	0
MXD1	0.01	0	-9999	-10000	0	0
STAT3	0.012	0	-9999	-10000	0	0
NFKB1	0.01	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.01	0	-9999	-10000	0	0
YY1/LSF/HDAC1	0.022	0	-9999	-10000	0	0
YY1/SAP30/HDAC1	0.021	0.002	-9999	-10000	0	0
EP300	0.01	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.012	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.01	0.019	-9999	-0.17	3	3
histone deacetylation	0.02	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.016	0.016	-9999	-10000	0	0
nuclear export	-0.02	0	-9999	-10000	0	0
PRKACA	0.01	0	-9999	-10000	0	0
GATAD2B	0.01	0	-9999	-10000	0	0
GATAD2A	0.01	0	-9999	-10000	0	0
GATA2/HDAC3	-0.035	0.1	-9999	-0.23	60	60
GATA1/HDAC1	0.012	0.004	-9999	-10000	0	0
GATA1/HDAC3	0.013	0.018	-9999	-10000	0	0
CHD4	0.01	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	0.01	0.033	-9999	-0.31	3	3
SIN3/HDAC complex/Mad/Max	0.02	0.002	-9999	-10000	0	0
NuRD Complex	0.024	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.026	0.017	-9999	-10000	0	0
SIN3B	0.01	0	-9999	-10000	0	0
MTA2	0.01	0	-9999	-10000	0	0
SIN3A	0.01	0	-9999	-10000	0	0
XPO1	0.01	0	-9999	-10000	0	0
SUMO1/HDAC1	0.018	0	-9999	-10000	0	0
HDAC complex	0.025	0	-9999	-10000	0	0
GATA1/Fog1	0.012	0.004	-9999	-10000	0	0
FKBP25/HDAC1/HDAC2	0.02	0	-9999	-10000	0	0
TNF	0.005	0.046	-9999	-0.44	3	3
negative regulation of cell growth	0.02	0.002	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.02	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.019	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.014	0.03	-9999	-0.28	3	3
SIN3/HDAC complex/NCoR1	0.019	0.002	-9999	-10000	0	0
TFCP2	0.01	0	-9999	-10000	0	0
NR2C1	0.01	0	-9999	-10000	0	0
MBD3	0.01	0	-9999	-10000	0	0
MBD2	0.01	0	-9999	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.01	0	-9999	-10000	0	0
HDAC3	0.01	0	-9999	-10000	0	0
VDR	0.002	0.059	-9999	-0.44	5	5
Cbp/p300/PCAF	0.02	0	-9999	-10000	0	0
EP300	0.01	0	-9999	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.022	0.013	-9999	-10000	0	0
KAT2B	0.01	0	-9999	-10000	0	0
MAPK14	0.01	0	-9999	-10000	0	0
AKT1	0.013	0.015	-9999	-10000	0	0
RAR alpha/9cRA/Cyclin H	0.027	0.027	-9999	-10000	0	0
mol:9cRA	0	0	-9999	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.021	0.013	-9999	-10000	0	0
CDC2	0	0	-9999	-10000	0	0
response to UV	0.001	0	-9999	-10000	0	0
RAR alpha/Jnk1	0.012	0.049	-9999	-0.35	5	5
NCOR2	0.01	0	-9999	-10000	0	0
VDR/VDR/Vit D3	0.002	0.042	-9999	-0.31	5	5
RXRs/RARs/NRIP1/9cRA	0.029	0.021	-9999	-10000	0	0
NCOA2	-0.031	0.13	-9999	-0.44	26	26
NCOA3	0.01	0	-9999	-10000	0	0
NCOA1	0.01	0	-9999	-10000	0	0
VDR/VDR/DNA	0.002	0.058	-9999	-0.44	5	5
RARG	0.01	0.001	-9999	-10000	0	0
RAR gamma1/9cRA	0.014	0.001	-9999	-10000	0	0
MAPK3	0.01	0	-9999	-10000	0	0
MAPK1	0.01	0	-9999	-10000	0	0
MAPK8	0.002	0.059	-9999	-0.44	5	5
mol:Vit D3	0	0	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.012	0.03	-9999	-10000	0	0
RARA	0.006	0.027	-9999	-0.19	5	5
negative regulation of phosphoinositide 3-kinase cascade	0	0	-9999	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.003	0.061	-9999	-0.2	18	18
PRKCA	0.011	0	-9999	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	0.029	0.02	-9999	-10000	0	0
RXRG	0.007	0.005	-9999	-10000	0	0
RXRA	0.007	0.023	-9999	-0.19	1	1
RXRB	0.009	0.005	-9999	-10000	0	0
VDR/Vit D3/DNA	0.002	0.042	-9999	-0.31	5	5
RBP1	0.01	0	-9999	-10000	0	0
CRBP1/9-cic-RA	0.007	0	-9999	-10000	0	0
RARB	0.011	0	-9999	-10000	0	0
PRKCG	0.006	0.005	-9999	-10000	0	0
MNAT1	0.01	0	-9999	-10000	0	0
RAR alpha/RXRs	0.014	0.021	-9999	-10000	0	0
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.028	0.02	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.023	0.022	-9999	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC3	0.029	0.02	-9999	-10000	0	0
positive regulation of DNA binding	0.013	0.024	-9999	-10000	0	0
NRIP1	0.029	0.019	-9999	-10000	0	0
RXRs/RARs	0.028	0.02	-9999	-10000	0	0
RXRs/RXRs/DNA/9cRA	0.011	0.017	-9999	-10000	0	0
PRKACA	0.01	0	-9999	-10000	0	0
CDK7	0.01	0	-9999	-10000	0	0
TFIIH	0.02	0	-9999	-10000	0	0
RAR alpha/9cRA	0.027	0.021	-9999	-10000	0	0
CCNH	0.01	0	-9999	-10000	0	0
CREBBP	0.01	0	-9999	-10000	0	0
RAR gamma2/9cRA	0.019	0.001	-9999	-10000	0	0

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.038	0.14	-9999	-0.44	31	31
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.01	0.001	-9999	-10000	0	0
TCEB1	0.01	0	-9999	-10000	0	0
HIF1A/p53	0.016	0.005	-9999	-10000	0	0
HIF1A	0.008	0.002	-9999	-10000	0	0
COPS5	0.01	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.029	0.002	-9999	-10000	0	0
FIH (dimer)	0.01	0	-9999	-10000	0	0
CDKN2A	0.002	0.004	-9999	-10000	0	0
ARNT/IPAS	-0.02	0.1	-9999	-0.31	31	31
HIF1AN	0.01	0	-9999	-10000	0	0
GNB2L1	0.01	0	-9999	-10000	0	0
HIF1A/ARNT	0.016	0.005	-9999	-10000	0	0
CUL2	0.01	0	-9999	-10000	0	0
OS9	0.01	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	0.02	0.002	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.016	0.005	-9999	-10000	0	0
PHD1-3/OS9	0.024	0.005	-9999	-10000	0	0
HIF1A/RACK1/Elongin B/Elongin C	0.024	0.004	-9999	-10000	0	0
VHL	0.01	0	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
HIF1A/JAB1	0.016	0.005	-9999	-10000	0	0
EGLN3	0.009	0.002	-9999	-10000	0	0
EGLN2	0.01	0	-9999	-10000	0	0
EGLN1	0.01	0	-9999	-10000	0	0
TP53	0.01	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.02	0.002	-9999	-10000	0	0
ARNT	0.01	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.01	0	-9999	-10000	0	0
HIF1A/p19ARF	0.003	0.006	-9999	-10000	0	0

×

Signaling events mediated by PRL

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
CCNE1	0.009	0.002	-9999	-10000	0	0
mol:Halofuginone	0.003	0	-9999	-10000	0	0
ITGA1	0.007	0.037	-9999	-0.44	2	2
CDKN1A	0.006	0.03	-9999	-10000	0	0
PRL-3/alpha Tubulin	0.015	0	-9999	-10000	0	0
mol:Ca2+	-0.018	0.065	-9999	-0.32	13	13
AGT	-0.01	0.093	-9999	-0.44	13	13
CCNA2	-0.007	0.058	-9999	-10000	0	0
TUBA1B	0.01	0	-9999	-10000	0	0
EGR1	-0.015	0.086	-9999	-0.31	23	23
CDK2/Cyclin E1	0.015	0.029	-9999	-10000	0	0
MAPK3	0.009	0	-9999	-10000	0	0
PRL-2 /Rab GGTase beta	0.015	0	-9999	-10000	0	0
MAPK1	0.009	0	-9999	-10000	0	0
PTP4A1	-0.007	0.064	-9999	-10000	0	0
PTP4A3	0.01	0	-9999	-10000	0	0
PTP4A2	0.01	0	-9999	-10000	0	0
ITGB1	0.009	0	-9999	-10000	0	0
SRC	0.01	0.001	-9999	-10000	0	0
RAC1	0.006	0.03	-9999	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0.015	0	-9999	-10000	0	0
PRL-1/ATF-5	-0.001	0.061	-9999	-10000	0	0
RABGGTA	0.01	0	-9999	-10000	0	0
BCAR1	-0.004	0	-9999	-10000	0	0
RHOC	0.006	0.03	-9999	-10000	0	0
RHOA	0.006	0.03	-9999	-10000	0	0
cell motility	0.008	0.033	-9999	-10000	0	0
PRL-1/alpha Tubulin	-0.001	0.061	-9999	-10000	0	0
PRL-3/alpha1 Integrin	0.012	0.027	-9999	-0.31	2	2
ROCK1	0.008	0.033	-9999	-10000	0	0
RABGGTB	0.01	0	-9999	-10000	0	0
CDK2	0.01	0	-9999	-10000	0	0
mitosis	-0.007	0.064	-9999	-10000	0	0
ATF5	0.01	0.001	-9999	-10000	0	0

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.01	0	-9999	-10000	0	0
SMAD2	0.005	0	-9999	-10000	0	0
SMAD3	0.015	0	-9999	-10000	0	0
SMAD3/SMAD4	0.022	0	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	0.02	0	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	0.026	0	-9999	-10000	0	0
PPM1A	0.01	0	-9999	-10000	0	0
CALM1	0.01	0	-9999	-10000	0	0
SMAD2/SMAD4	0.011	0	-9999	-10000	0	0
MAP3K1	0.01	0	-9999	-10000	0	0
TRAP-1/SMAD4	0.009	0.042	-9999	-0.31	5	5
MAPK3	0.01	0	-9999	-10000	0	0
MAPK1	0.01	0	-9999	-10000	0	0
NUP214	0.01	0	-9999	-10000	0	0
CTDSP1	0.01	0	-9999	-10000	0	0
CTDSP2	0.01	0	-9999	-10000	0	0
CTDSPL	0.01	0	-9999	-10000	0	0
KPNB1	0.01	0	-9999	-10000	0	0
TGFBRAP1	0.002	0.059	-9999	-0.44	5	5
UBE2I	0.01	0	-9999	-10000	0	0
NUP153	0.01	0	-9999	-10000	0	0
KPNA2	0.01	0	-9999	-10000	0	0
PIAS4	0.01	0	-9999	-10000	0	0

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.011	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.035	0.005	-9999	-10000	0	0
ERC1	0.01	0	-9999	-10000	0	0
RIP2/NOD2	0.014	0.004	-9999	-10000	0	0
NFKBIA	0.013	0	-9999	-10000	0	0
BIRC2	0.01	0	-9999	-10000	0	0
IKBKB	0.01	0	-9999	-10000	0	0
RIPK2	0.01	0	-9999	-10000	0	0
IKBKG	0.018	0.005	-9999	-10000	0	0
IKK complex/A20	0.031	0.023	-9999	-10000	0	0
NEMO/A20/RIP2	0.01	0	-9999	-10000	0	0
XPO1	0.01	0	-9999	-10000	0	0
NEMO/ATM	0.026	0.007	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.01	0	-9999	-10000	0	0
Exportin 1/RanGTP	0.013	0	-9999	-10000	0	0
IKK complex/ELKS	0.025	0.006	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0.02	0	-9999	-10000	0	0
NOD2	0.009	0.002	-9999	-10000	0	0
NFKB1	0.011	0	-9999	-10000	0	0
RELA	0.011	0	-9999	-10000	0	0
MALT1	0.01	0	-9999	-10000	0	0
cIAP1/UbcH5C	0.015	0	-9999	-10000	0	0
ATM	0.01	0	-9999	-10000	0	0
TNF/TNFR1A	0.01	0.033	-9999	-0.31	3	3
TRAF6	0.01	0	-9999	-10000	0	0
PRKCA	0.01	0	-9999	-10000	0	0
CHUK	0.01	0	-9999	-10000	0	0
UBE2D3	0.01	0	-9999	-10000	0	0
TNF	0.005	0.046	-9999	-0.44	3	3
NF kappa B1 p50/RelA	0.025	0	-9999	-10000	0	0
BCL10	0.01	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.013	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.011	0	-9999	-10000	0	0
TNFRSF1A	0.01	0	-9999	-10000	0	0
IKK complex	0.031	0.007	-9999	-10000	0	0
CYLD	0.01	0	-9999	-10000	0	0
IKK complex/PKC alpha	0.035	0.006	-9999	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
PLK2	0.009	0.003	-9999	-9999
PLK4	0.01	0.001	-9999	-9999
regulation of centriole replication	0.008	0.002	-9999	-9999

×

Visual signal transduction: Cones

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.015	0.014	-9999	-0.22	1	1
RGS9BP	0.008	0.026	-9999	-0.44	1	1
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0.002	0.004	-9999	-10000	0	0
mol:Na +	0.004	0.004	-9999	-10000	0	0
mol:ADP	0.003	0.003	-9999	-10000	0	0
GNAT2	0.008	0.004	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.015	0.035	-9999	-0.24	5	5
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0.007	0.004	-9999	-10000	0	0
GRK7	0.005	0.005	-9999	-10000	0	0
CNGB3	0.003	0.004	-9999	-10000	0	0
Cone Metarhodopsin II/X-Arrestin	0.002	0.003	-9999	-10000	0	0
mol:Ca2+	0.002	0.002	-9999	-10000	0	0
Cone PDE6	0.016	0.03	-9999	-0.22	4	4
Cone Metarhodopsin II	0.005	0.004	-9999	-10000	0	0
Na + (4 Units)	0.004	0.005	-9999	-10000	0	0
GNAT2/GDP	0.017	0.03	-9999	-0.2	5	5
GNB5	0.01	0	-9999	-10000	0	0
mol:GMP (4 units)	0.004	0.003	-9999	-10000	0	0
Cone Transducin	0.016	0.015	-9999	-0.23	1	1
SLC24A2	0.001	0.003	-9999	-10000	0	0
GNB3/GNGT2	0.013	0.019	-9999	-0.31	1	1
GNB3	0.009	0.002	-9999	-10000	0	0
GNAT2/GTP	0.006	0.003	-9999	-10000	0	0
CNGA3	0.003	0.005	-9999	-10000	0	0
ARR3	0.002	0.004	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	0.004	0.004	-9999	-10000	0	0
mol:Pi	0.014	0.034	-9999	-0.24	5	5
Cone CNG Channel	0.009	0.005	-9999	-10000	0	0
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	0.001	0.003	-9999	-10000	0	0
RGS9	0.003	0.052	-9999	-0.44	4	4
PDE6C	0.003	0.005	-9999	-10000	0	0
GNGT2	0.008	0.026	-9999	-0.44	1	1
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.002	0.004	-9999	-10000	0	0

×

Circadian rhythm 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.025	0.012	-9999	-10000	0	0
CLOCK	0.007	0.046	-9999	-0.44	3	3
TIMELESS/CRY2	0.021	0.013	-9999	-10000	0	0
DEC1/BMAL1	0.01	0.003	-9999	-10000	0	0
ATR	0.01	0	-9999	-10000	0	0
NR1D1	0.015	0.009	-9999	-10000	0	0
ARNTL	0.011	0.002	-9999	-10000	0	0
TIMELESS	0.017	0.015	-9999	-10000	0	0
NPAS2	0.01	0.026	-9999	-0.44	1	1
CRY2	0.01	0	-9999	-10000	0	0
mol:CO	-0.007	0.007	-9999	-10000	0	0
CHEK1	0.01	0	-9999	-10000	0	0
mol:HEME	0.007	0.007	-9999	-10000	0	0
PER1	0.01	0	-9999	-10000	0	0
BMAL/CLOCK/NPAS2	0.024	0.034	-9999	-0.26	4	4
BMAL1/CLOCK	0.021	0.038	-9999	-10000	0	0
S phase of mitotic cell cycle	0.025	0.012	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	0.026	0.012	-9999	-10000	0	0
mol:NADPH	0.007	0.007	-9999	-10000	0	0
PER1/TIMELESS	0.021	0.013	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	0.002	0.004	-9999	-10000	0	0

×

JNK signaling in the CD4+ TCR 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
LAT/GRAP2/SLP76/HPK1	0.02	0.01	-10000	0	-10000	0	0
MAP4K1	0.008	0.003	-10000	0	-10000	0	0
MAP3K8	0.01	0	-10000	0	-10000	0	0
PRKCB	0.01	0.001	-10000	0	-10000	0	0
DBNL	0.01	0	-10000	0	-10000	0	0
CRKL	0.01	0	-10000	0	-10000	0	0
MAP3K1	0.021	0.012	-10000	0	-10000	0	0
JUN	0.012	0.065	-10000	0	-0.48	5	5
MAP3K7	0.021	0.012	-10000	0	-10000	0	0
GRAP2	0.009	0.002	-10000	0	-10000	0	0
CRK	0.01	0	-10000	0	-10000	0	0
MAP2K4	0.028	0.021	0.16	2	-10000	0	2
LAT	0.009	0.003	-10000	0	-10000	0	0
LCP2	0.01	0.002	-10000	0	-10000	0	0
MAPK8	0.011	0.069	-10000	0	-0.5	5	5
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.021	0.012	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/HPK1/HIP-55	0.023	0.012	-10000	0	-10000	0	0

×

a4b1 and a4b7 Integrin 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	Mean.of.Down.Perturbations
ITGB1	0.01	0	-9999	-9999
ITGB7	0.01	0	-9999	-9999
ITGA4	0.01	0.001	-9999	-9999
alpha4/beta7 Integrin	0.015	0.001	-9999	-9999
alpha4/beta1 Integrin	0.015	0.001	-9999	-9999

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.014	0.002	-9999	-10000	0	0
BIRC5	0.006	0.005	-9999	-10000	0	0
NFKBIA	0.01	0.002	-9999	-10000	0	0
CPEB1	0.003	0.052	-9999	-0.44	4	4
AKT1	0.01	0.002	-9999	-10000	0	0
NDEL1	0.01	0	-9999	-10000	0	0
Aurora A/BRCA1	0.013	0.002	-9999	-10000	0	0
NDEL1/TACC3	0.018	0.003	-9999	-10000	0	0
GADD45A	0.01	0	-9999	-10000	0	0
GSK3B	0.009	0.001	-9999	-10000	0	0
PAK1/Aurora A	0.014	0.002	-9999	-10000	0	0
MDM2	0.01	0	-9999	-10000	0	0
JUB	0.01	0	-9999	-10000	0	0
TPX2	0.007	0.004	-9999	-10000	0	0
TP53	0.013	0.002	-9999	-10000	0	0
DLG7	0.005	0.004	-9999	-10000	0	0
AURKAIP1	0.01	0	-9999	-10000	0	0
ARHGEF7	0.01	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	0.019	0.003	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.013	0.002	-9999	-10000	0	0
AURKA	0.007	0.005	-9999	-10000	0	0
AURKB	0.004	0.004	-9999	-10000	0	0
CDC25B	0.012	0.002	-9999	-10000	0	0
G2/M transition checkpoint	0.013	0.002	-9999	-10000	0	0
mRNA polyadenylation	0.008	0.028	-9999	-0.23	4	4
Aurora A/CPEB	0.009	0.028	-9999	-0.23	4	4
Aurora A/TACC1/TRAP/chTOG	0.025	0.003	-9999	-10000	0	0
BRCA1	0.01	0.001	-9999	-10000	0	0
centrosome duplication	0.014	0.002	-9999	-10000	0	0
regulation of centrosome cycle	0.018	0.003	-9999	-10000	0	0
spindle assembly	0.024	0.003	-9999	-10000	0	0
TDRD7	0.01	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	0.015	0.011	-9999	-10000	0	0
CENPA	0.005	0.005	-9999	-10000	0	0
Aurora A/PP2A	0.014	0.002	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.013	0.003	-9999	-10000	0	0
negative regulation of DNA binding	0.013	0.002	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0.015	0	-9999	-10000	0	0
RASA1	0.01	0	-9999	-10000	0	0
Ajuba/Aurora A	0.013	0.002	-9999	-10000	0	0
mitotic prometaphase	0	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.007	0.005	-9999	-10000	0	0
TACC1	0.01	0	-9999	-10000	0	0
TACC3	0.01	0.001	-9999	-10000	0	0
Aurora A/Antizyme1	0.02	0.003	-9999	-10000	0	0
Aurora A/RasGAP	0.014	0.002	-9999	-10000	0	0
OAZ1	0.01	0	-9999	-10000	0	0
RAN	0.01	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.009	0.001	-9999	-10000	0	0
GIT1	0.01	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0.02	0	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	0.007	0.004	-9999	-10000	0	0
PPP2R5D	0.01	0.001	-9999	-10000	0	0
Aurora A/TPX2	0.01	0.006	-9999	-10000	0	0
PAK1	0.01	0	-9999	-10000	0	0
CKAP5	0.01	0	-9999	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
PLAUR	0.016	0.004	-9999	-9999
regulation of axonogenesis	-0.015	0.012	-9999	-9999
myoblast fusion	-0.017	0.023	-9999	-9999
mol:GTP	0.008	0.002	-9999	-9999
regulation of calcium-dependent cell-cell adhesion	-0.027	0.019	-9999	-9999
ARF1/GTP	0.013	0.004	-9999	-9999
mol:GM1	0.009	0.013	-9999	-9999
mol:Choline	0.014	0.012	-9999	-9999
lamellipodium assembly	0.011	0.004	-9999	-9999
MAPK3	0.021	0.024	-9999	-9999
ARF6/GTP/NME1/Tiam1	0.028	0.019	-9999	-9999
ARF1	0.01	0	-9999	-9999
ARF6/GDP	0.017	0.023	-9999	-9999
ARF1/GDP	0.02	0.021	-9999	-9999
ARF6	0.013	0.007	-9999	-9999
RAB11A	0.01	0	-9999	-9999
TIAM1	0.011	0.002	-9999	-9999
fibronectin binding	0	0	-9999	-9999
MAPK1	0.021	0.024	-9999	-9999
actin filament bundle formation	-0.015	0.004	-9999	-9999
KALRN	0.009	0.003	-9999	-9999
RAB11FIP3/RAB11A	0.015	0	-9999	-9999
RhoA/GDP	0.015	0.004	-9999	-9999
NME1	0.011	0.002	-9999	-9999
Rac1/GDP	0.015	0.004	-9999	-9999
substrate adhesion-dependent cell spreading	0.008	0.002	-9999	-9999
cortical actin cytoskeleton organization	0.011	0.004	-9999	-9999
RAC1	0.01	0	-9999	-9999
liver development	0.008	0.002	-9999	-9999
ARF6/GTP	0.008	0.002	-9999	-9999
RhoA/GTP	0.013	0.004	-9999	-9999
mol:GDP	0.009	0.003	-9999	-9999
ARF6/GTP/RAB11FIP3/RAB11A	0.023	0.01	-9999	-9999
RHOA	0.01	0	-9999	-9999
PLD1	0.014	0.013	-9999	-9999
RAB11FIP3	0.01	0	-9999	-9999
tube morphogenesis	0.011	0.004	-9999	-9999
ruffle organization	0.015	0.012	-9999	-9999
regulation of epithelial cell migration	0.008	0.002	-9999	-9999
PLD2	0.014	0.013	-9999	-9999
PIP5K1A	0.015	0.012	-9999	-9999
mol:Phosphatidic acid	0.014	0.012	-9999	-9999
Rac1/GTP	0.011	0.004	-9999	-9999

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
INCENP	0.01	0	-9999	-9999
Aurora C/Aurora B/INCENP	0.01	0.009	-9999	-9999
metaphase	0	0	-9999	-9999
mitosis	0	0	-9999	-9999
H3F3B	0.004	0.004	-9999	-9999
AURKB	0.005	0.005	-9999	-9999
AURKC	0.01	0.001	-9999	-9999

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.03	0.005	-9999	-10000	0	0
CRKL	0.017	0.004	-9999	-10000	0	0
mol:DAG	0.022	0.002	-9999	-10000	0	0
HRAS	0.02	0.004	-9999	-10000	0	0
MAPK8	0.01	0.033	-9999	-0.24	5	5
RAP1A	0.017	0.004	-9999	-10000	0	0
GAB1	0.017	0.004	-9999	-10000	0	0
MAPK14	0.014	0.005	-9999	-10000	0	0
EPO	0.008	0.005	-9999	-10000	0	0
PLCG1	0.022	0.002	-9999	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0.011	0	-9999	-10000	0	0
RAPGEF1	0.01	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.019	0.017	-9999	-0.27	1	1
GAB1/SHC/GRB2/SOS1	0.028	0.003	-9999	-10000	0	0
EPO/EPOR (dimer)	0.015	0.004	-9999	-10000	0	0
IRS2	0.017	0.005	-9999	-10000	0	0
STAT1	0.026	0.004	-9999	-10000	0	0
STAT5B	0.024	0.003	-9999	-10000	0	0
cell proliferation	0.009	0.031	-9999	-0.22	5	5
GAB1/SHIP/PIK3R1/SHP2/SHC	0.021	0.004	-9999	-10000	0	0
TEC	0.017	0.004	-9999	-10000	0	0
SOCS3	0.008	0.026	-9999	-0.44	1	1
STAT1 (dimer)	0.026	0.004	-9999	-10000	0	0
JAK2	0.011	0	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.032	0.004	-9999	-10000	0	0
EPO/EPOR	0.015	0.004	-9999	-10000	0	0
LYN	0.011	0	-9999	-10000	0	0
TEC/VAV2	0.023	0.004	-9999	-10000	0	0
elevation of cytosolic calcium ion concentration	0.011	0	-9999	-10000	0	0
SHC1	0.01	0	-9999	-10000	0	0
EPO/EPOR (dimer)/LYN	0.023	0.004	-9999	-10000	0	0
mol:IP3	0.022	0.002	-9999	-10000	0	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.026	0.007	-9999	-10000	0	0
SH2B3	0.011	0	-9999	-10000	0	0
NFKB1	0.014	0.005	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2/SOCS3	0.006	0.012	-9999	-0.2	1	1
PTPN6	0.016	0.005	-9999	-10000	0	0
TEC/VAV2/GRB2	0.028	0.004	-9999	-10000	0	0
EPOR	0.011	0	-9999	-10000	0	0
INPP5D	0.009	0.002	-9999	-10000	0	0
mol:GDP	0.027	0.003	-9999	-10000	0	0
SOS1	0.01	0	-9999	-10000	0	0
PLCG2	-0.015	0.1	-9999	-0.44	16	16
CRKL/CBL/C3G	0.028	0.004	-9999	-10000	0	0
VAV2	0.017	0.004	-9999	-10000	0	0
CBL	0.017	0.004	-9999	-10000	0	0
SHC/Grb2/SOS1	0.019	0.002	-9999	-10000	0	0
STAT5A	0.024	0.003	-9999	-10000	0	0
GRB2	0.01	0	-9999	-10000	0	0
STAT5 (dimer)	0.035	0.003	-9999	-10000	0	0
LYN/PLCgamma2	-0.003	0.074	-9999	-0.31	16	16
PTPN11	0.01	0	-9999	-10000	0	0
BTK	0.012	0.009	-9999	-10000	0	0
BCL2	0.03	0.005	-9999	-10000	0	0

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.009	0.013	-10000	0	-10000	0	0
BUB1B	0.019	0.021	0.088	7	-10000	0	7
PLK1	0.011	0.008	-10000	0	-10000	0	0
PLK1S1	0.009	0.004	-10000	0	-10000	0	0
KIF2A	0.011	0.007	-10000	0	-10000	0	0
regulation of mitotic centrosome separation	0.011	0.008	-10000	0	-10000	0	0
GOLGA2	0.01	0	-10000	0	-10000	0	0
Hec1/SPC24	0.015	0.008	-10000	0	-10000	0	0
WEE1	0.016	0.008	-10000	0	-10000	0	0
cytokinesis	0.031	0.039	0.12	4	-0.16	5	9
PP2A-alpha B56	0.028	0.005	-10000	0	-10000	0	0
AURKA	0.01	0.006	-10000	0	-10000	0	0
PICH/PLK1	0.017	0.008	-10000	0	-10000	0	0
CENPE	0.017	0.026	0.11	22	-10000	0	22
RhoA/GTP	0.007	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.011	0.007	-10000	0	-10000	0	0
PPP2CA	0.01	0	-10000	0	-10000	0	0
FZR1	0.01	0	-10000	0	-10000	0	0
TPX2	0.014	0.012	-10000	0	-10000	0	0
PAK1	0.01	0	-10000	0	-10000	0	0
SPC24	0.008	0.004	-10000	0	-10000	0	0
FBXW11	0.01	0	-10000	0	-10000	0	0
CLSPN	0.013	0.011	-10000	0	-10000	0	0
GORASP1	0.01	0	-10000	0	-10000	0	0
metaphase	0.001	0.002	0.006	6	-10000	0	6
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.006	0.004	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
STAG2	0.01	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.013	0.002	-10000	0	-10000	0	0
spindle elongation	0.011	0.008	-10000	0	-10000	0	0
ODF2	0.01	0	-10000	0	-10000	0	0
BUB1	0.009	0.007	-10000	0	-10000	0	0
TPT1	0.009	0.004	-10000	0	-10000	0	0
CDC25C	0.017	0.014	-10000	0	-10000	0	0
CDC25B	0.01	0.001	-10000	0	-10000	0	0
SGOL1	0.009	0.013	-10000	0	-10000	0	0
RHOA	0.01	0	-10000	0	-10000	0	0
CCNB1/CDK1	0.014	0.007	-10000	0	-10000	0	0
CDC14B	0.004	0	-10000	0	-10000	0	0
CDC20	0.009	0.003	-10000	0	-10000	0	0
PLK1/PBIP1	0.009	0.007	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
FBXO5	0.011	0.007	-10000	0	-10000	0	0
CDC2	0.001	0	-10000	0	-10000	0	0
NDC80	0.009	0.003	-10000	0	-10000	0	0
metaphase plate congression	0.01	0.006	-10000	0	-10000	0	0
ERCC6L	0.017	0.007	-10000	0	-10000	0	0
NLP/gamma Tubulin	0.008	0.005	-10000	0	-10000	0	0
microtubule cytoskeleton organization	0.009	0.004	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	0	0	-10000	0	-10000	0	0
PPP1R12A	0.01	0	-10000	0	-10000	0	0
interphase	0	0	-10000	0	-10000	0	0
PLK1/PRC1-2	0.012	0.009	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP/PLK1	0.024	0.005	-10000	0	-10000	0	0
RAB1A	0.01	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.009	0.006	-10000	0	-10000	0	0
mitotic prometaphase	0	0	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.014	0.005	-10000	0	-10000	0	0
microtubule-based process	0.008	0.006	-10000	0	-10000	0	0
Golgi organization	0.011	0.008	-10000	0	-10000	0	0
Cohesin/SA2	0.015	0.007	-10000	0	-10000	0	0
PPP1CB/MYPT1	0.014	0	-10000	0	-10000	0	0
KIF20A	0.006	0.005	-10000	0	-10000	0	0
APC/C/CDC20	0.013	0.006	-10000	0	-10000	0	0
PPP2R1A	0.01	0	-10000	0	-10000	0	0
chromosome segregation	0.009	0.007	-10000	0	-10000	0	0
PRC1	0.009	0.002	-10000	0	-10000	0	0
ECT2	0.012	0.01	0.1	2	-10000	0	2
C13orf34	0.01	0.006	-10000	0	-10000	0	0
NUDC	0.01	0.006	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	0.019	0.021	0.088	7	-10000	0	7
spindle assembly	0.01	0.007	-10000	0	-10000	0	0
spindle stabilization	0.009	0.004	-10000	0	-10000	0	0
APC/C/HCDH1	0.011	0	-10000	0	-10000	0	0
MKLP2/PLK1	0.009	0.006	-10000	0	-10000	0	0
CCNB1	0.01	0.001	-10000	0	-10000	0	0
PPP1CB	0.01	0	-10000	0	-10000	0	0
BTRC	0.01	0	-10000	0	-10000	0	0
ROCK2	0.007	0.052	-10000	0	-0.38	5	5
TUBG1	0.009	0.004	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.006	0.005	-10000	0	-10000	0	0
MLF1IP	0.004	0.002	-10000	0	-10000	0	0
INCENP	0.01	0	-10000	0	-10000	0	0

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.001	0.042	-9999	-0.23	1	1
CaM/Ca2+	0.007	0	-9999	-10000	0	0
AKT1	0.01	0	-9999	-10000	0	0
AKT2	0.01	0	-9999	-10000	0	0
STXBP4	0.01	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
mol:glucose	-0.006	0.043	-9999	-0.25	1	1
YWHAZ	0.01	0	-9999	-10000	0	0
CALM1	0.01	0	-9999	-10000	0	0
YWHAQ	0.01	0	-9999	-10000	0	0
TBC1D4	0.009	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
YWHAH	0.01	0	-9999	-10000	0	0
YWHAB	0.01	0	-9999	-10000	0	0
SNARE/Synip	0.02	0	-9999	-10000	0	0
YWHAG	0.01	0	-9999	-10000	0	0
ASIP	0.005	0.005	-9999	-10000	0	0
PRKCI	0.01	0	-9999	-10000	0	0
AS160/CaM/Ca2+	0.007	0	-9999	-10000	0	0
RHOQ	0.01	0	-9999	-10000	0	0
GYS1	0.011	0	-9999	-10000	0	0
PRKCZ	0.01	0	-9999	-10000	0	0
TRIP10	0.01	0	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.013	0	-9999	-10000	0	0
AS160/14-3-3	0.007	0.026	-9999	-10000	0	0
VAMP2	0.01	0	-9999	-10000	0	0
SLC2A4	-0.007	0.046	-9999	-0.27	1	1
STX4	0.01	0	-9999	-10000	0	0
GSK3B	0.012	0	-9999	-10000	0	0
SFN	-0.002	0.058	-9999	-0.44	5	5
LNPEP	0.01	0	-9999	-10000	0	0
YWHAE	0.01	0	-9999	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.009	0	-9999	-10000	0	0
BAD/BCL-XL/YWHAZ	0.02	0	-9999	-10000	0	0
CDKN1B	0.014	0.002	-9999	-10000	0	0
CDKN1A	0.015	0.011	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
PRKDC	0.01	0	-9999	-10000	0	0
FOXO3	0.014	0.002	-9999	-10000	0	0
AKT1	0.013	0.001	-9999	-10000	0	0
BAD	0.01	0	-9999	-10000	0	0
AKT3	0.008	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
FOXO4	0.014	0.002	-9999	-10000	0	0
AKT1/ASK1	0.018	0.001	-9999	-10000	0	0
BAD/YWHAZ	0.02	0	-9999	-10000	0	0
RICTOR	0.01	0	-9999	-10000	0	0
RAF1	0.01	0	-9999	-10000	0	0
JNK cascade	-0.017	0.001	-9999	-10000	0	0
TSC1	0.014	0.002	-9999	-10000	0	0
YWHAZ	0.01	0	-9999	-10000	0	0
AKT1/RAF1	0.018	0.001	-9999	-10000	0	0
EP300	0.01	0	-9999	-10000	0	0
mol:GDP	0.013	0.001	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
TSC2	0.014	0.002	-9999	-10000	0	0
YWHAQ	0.01	0	-9999	-10000	0	0
TBC1D4	0.008	0	-9999	-10000	0	0
MAP3K5	0.01	0	-9999	-10000	0	0
MAPKAP1	0.01	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.026	0.021	-9999	-10000	0	0
YWHAH	0.01	0	-9999	-10000	0	0
AKT1S1	0.014	0.002	-9999	-10000	0	0
CASP9	0.014	0.002	-9999	-10000	0	0
YWHAB	0.01	0	-9999	-10000	0	0
p27Kip1/KPNA1	0.019	0.001	-9999	-10000	0	0
GBL	0	0	-9999	-10000	0	0
PDK1/Src/Hsp90	0.02	0.001	-9999	-10000	0	0
YWHAE	0.01	0	-9999	-10000	0	0
SRC	0.01	0.001	-9999	-10000	0	0
AKT2/p21CIP1	0.017	0.01	-9999	-10000	0	0
KIAA1303	0	0	-9999	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.009	0.001	-9999	-10000	0	0
CHUK	0.014	0.002	-9999	-10000	0	0
BAD/BCL-XL	0.023	0.001	-9999	-10000	0	0
mTORC2	0.013	0	-9999	-10000	0	0
AKT2	0.008	0	-9999	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.032	0.024	-9999	-10000	0	0
PDPK1	0.01	0	-9999	-10000	0	0
MDM2	0.014	0.002	-9999	-10000	0	0
MAPKKK cascade	-0.018	0.001	-9999	-10000	0	0
MDM2/Cbp/p300	0.024	0.001	-9999	-10000	0	0
TSC1/TSC2	0.015	0.001	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.023	0.001	-9999	-10000	0	0
glucose import	0.007	0.019	-9999	-0.23	2	2
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.012	0.001	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	0.007	0.02	-9999	-0.23	2	2
GSK3A	0.014	0.002	-9999	-10000	0	0
FOXO1	0.014	0.002	-9999	-10000	0	0
GSK3B	0.014	0.002	-9999	-10000	0	0
SFN	-0.002	0.058	-9999	-0.44	5	5
G1/S transition of mitotic cell cycle	0.015	0.001	-9999	-10000	0	0
p27Kip1/14-3-3 family	0.008	0.025	-9999	-10000	0	0
PRKACA	0.01	0	-9999	-10000	0	0
KPNA1	0.01	0	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
YWHAG	0.01	0	-9999	-10000	0	0
RHEB	0.01	0	-9999	-10000	0	0
CREBBP	0.01	0	-9999	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.014	0.001	-9999	-10000	0	0
CRKL	0.01	0	-9999	-10000	0	0
Rac1/GDP	0.007	0	-9999	-10000	0	0
DOCK1	0.01	0	-9999	-10000	0	0
ITGA4	0.01	0.001	-9999	-10000	0	0
alpha4/beta7 Integrin/MAdCAM1	0.021	0.009	-9999	-10000	0	0
EPO	0.007	0.005	-9999	-10000	0	0
alpha4/beta7 Integrin	0.015	0.001	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin	0.015	0.001	-9999	-10000	0	0
EPO/EPOR (dimer)	0.012	0.004	-9999	-10000	0	0
lamellipodium assembly	0.016	0.003	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
PI3K	0.015	0	-9999	-10000	0	0
ARF6	0.01	0	-9999	-10000	0	0
JAK2	0.015	0.002	-9999	-10000	0	0
PXN	0.01	0	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
MADCAM1	0.007	0.004	-9999	-10000	0	0
cell adhesion	0.02	0.008	-9999	-10000	0	0
CRKL/CBL	0.015	0	-9999	-10000	0	0
ITGB1	0.01	0	-9999	-10000	0	0
SRC	0.02	0.026	-9999	-0.23	1	1
ITGB7	0.01	0	-9999	-10000	0	0
RAC1	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.016	0.017	-9999	-0.26	1	1
p130Cas/Crk/Dock1	0.029	0.024	-9999	-0.19	1	1
VCAM1	0.007	0.026	-9999	-0.44	1	1
RHOA	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.025	0.001	-9999	-10000	0	0
BCAR1	0.019	0.027	-9999	-0.21	1	1
EPOR	0.01	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.01	0	-9999	-10000	0	0
GIT1	0.01	0	-9999	-10000	0	0
Rac1/GTP	0.017	0.003	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.01	0	-9999	-10000	0	0
HDAC4	0.008	0.026	-9999	-0.44	1	1
induction of apoptosis	0	0	-9999	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.007	0.001	-9999	-10000	0	0
CDKN1A	0.003	0	-9999	-10000	0	0
KAT2B	0.01	0	-9999	-10000	0	0
BAX	0.01	0.001	-9999	-10000	0	0
FOXO3	-0.003	0	-9999	-10000	0	0
FOXO1	0.01	0	-9999	-10000	0	0
FOXO4	0.01	0	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
XRCC6	0.01	0	-9999	-10000	0	0
TAT	0.008	0.004	-9999	-10000	0	0
mol:Lysophosphatidic acid	0	0	-9999	-10000	0	0
MYOD1	0.005	0.002	-9999	-10000	0	0
PPARGC1A	-0.001	0.069	-9999	-0.44	7	7
FHL2	0.008	0.026	-9999	-0.44	1	1
response to nutrient levels	0	0	-9999	-10000	0	0
KU70/SIRT1	0.013	0.002	-9999	-10000	0	0
HIST2H4A	0.007	0.001	-9999	-10000	0	0
SIRT1/FOXO3a	0.004	0.001	-9999	-10000	0	0
SIRT1	0.008	0.001	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
SIRT1/MEF2D/HDAC4	0.017	0.017	-9999	-0.26	1	1
SIRT1/Histone H1b	0.012	0.004	-9999	-10000	0	0
apoptosis	-0.018	0.003	-9999	-10000	0	0
SIRT1/PGC1A	0.005	0.042	-9999	-0.26	7	7
p53/SIRT1	0.01	0.002	-9999	-10000	0	0
SIRT1/FOXO4	0.012	0.002	-9999	-10000	0	0
FOXO1/FHL2/SIRT1	0.016	0.015	-9999	-0.23	1	1
HIST1H1E	0.009	0.001	-9999	-10000	0	0
SIRT1/p300	0.013	0.002	-9999	-10000	0	0
muscle cell differentiation	-0.012	0.003	-9999	-10000	0	0
TP53	0.008	0.001	-9999	-10000	0	0
KU70/SIRT1/BAX	0.018	0.003	-9999	-10000	0	0
CREBBP	0.01	0	-9999	-10000	0	0
MEF2D	0.01	0	-9999	-10000	0	0
HIV-1 Tat/SIRT1	0.011	0.004	-9999	-10000	0	0
ACSS2	0.007	0.001	-9999	-10000	0	0
SIRT1/PCAF/MYOD	0.012	0.003	-9999	-10000	0	0

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.01	0.001	-9999	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0.014	0.001	-9999	-10000	0	0
MAP2K4	0.018	0.003	-9999	-10000	0	0
IKBKB	0.01	0	-9999	-10000	0	0
TNFRSF10B	0.01	0.001	-9999	-10000	0	0
TNFRSF10A	0.01	0	-9999	-10000	0	0
SMPD1	0.008	0.001	-9999	-10000	0	0
IKBKG	0.01	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
TNFRSF10D	0.01	0	-9999	-10000	0	0
TRAIL/TRAILR2	0.014	0.002	-9999	-10000	0	0
TRAIL/TRAILR3	0.012	0.019	-9999	-0.31	1	1
TRAIL/TRAILR1	0.014	0.001	-9999	-10000	0	0
TRAIL/TRAILR4	0.014	0.001	-9999	-10000	0	0
TRAIL/TRAILR1/DAP3/GTP	0.019	0.002	-9999	-10000	0	0
IKK complex	0.018	0.003	-9999	-10000	0	0
RIPK1	0.01	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
DAP3/GTP	0.007	0	-9999	-10000	0	0
MAPK3	0.009	0.001	-9999	-10000	0	0
MAP3K1	0.018	0.003	-9999	-10000	0	0
TRAILR4 (trimer)	0.01	0	-9999	-10000	0	0
TRADD	0.01	0	-9999	-10000	0	0
TRAILR1 (trimer)	0.01	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.017	0.002	-9999	-10000	0	0
CFLAR	0.01	0	-9999	-10000	0	0
MAPK1	0.009	0.001	-9999	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP	0.029	0.003	-9999	-10000	0	0
mol:ceramide	0.008	0.001	-9999	-10000	0	0
FADD	0.01	0	-9999	-10000	0	0
MAPK8	0.016	0.028	-9999	-10000	0	0
TRAF2	0.01	0	-9999	-10000	0	0
TRAILR3 (trimer)	0.008	0.026	-9999	-0.44	1	1
CHUK	0.01	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD	0.02	0.002	-9999	-10000	0	0
DAP3	0.01	0	-9999	-10000	0	0
CASP10	0.008	0.001	-9999	-10000	0	0
JNK cascade	0.014	0.001	-9999	-10000	0	0
TRAIL (trimer)	0.01	0.001	-9999	-10000	0	0
TNFRSF10C	0.008	0.026	-9999	-0.44	1	1
TRAIL/TRAILR1/DAP3/GTP/FADD	0.023	0.002	-9999	-10000	0	0
TRAIL/TRAILR2/FADD	0.02	0.003	-9999	-10000	0	0
cell death	0.008	0.001	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.017	0.002	-9999	-10000	0	0
TRAILR2 (trimer)	0.01	0.001	-9999	-10000	0	0
CASP8	0.006	0.001	-9999	-10000	0	0
negative regulation of caspase activity	0	0	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.029	0.004	-9999	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.02	0.02	-9999	-10000	0	0
BAG4	0.01	0	-9999	-10000	0	0
BAD	0.012	0.009	-9999	-10000	0	0
NFKBIA	0.01	0	-9999	-10000	0	0
BIRC3	0.009	0.002	-9999	-10000	0	0
BAX	0.012	0.011	-9999	-10000	0	0
EnzymeConsortium:3.1.4.12	0.007	0.007	-9999	-10000	0	0
IKBKB	0.023	0.02	-9999	-10000	0	0
MAP2K2	0.014	0.011	-9999	-10000	0	0
MAP2K1	0.014	0.011	-9999	-10000	0	0
SMPD1	0.009	0.007	-9999	-10000	0	0
GO:0005551	0	0	-9999	-10000	0	0
FADD/Caspase 8	0.025	0.02	-9999	-10000	0	0
MAP2K4	0.013	0.009	-9999	-10000	0	0
protein ubiquitination	0.023	0.02	-9999	-10000	0	0
EnzymeConsortium:2.7.1.37	0.015	0.013	-9999	-10000	0	0
response to UV	0	0	-9999	-0.001	3	3
RAF1	0.013	0.011	-9999	-10000	0	0
CRADD	0.01	0	-9999	-10000	0	0
mol:ceramide	0.011	0.01	-9999	-10000	0	0
I-kappa-B-alpha/RELA/p50/ubiquitin	0.013	0	-9999	-10000	0	0
MADD	0.01	0	-9999	-10000	0	0
MAP3K1	0.012	0.009	-9999	-10000	0	0
TRADD	0.01	0	-9999	-10000	0	0
RELA/p50	0.01	0	-9999	-10000	0	0
MAPK3	0.015	0.011	-9999	-10000	0	0
MAPK1	0.015	0.011	-9999	-10000	0	0
p50/RELA/I-kappa-B-alpha	0.015	0	-9999	-10000	0	0
FADD	0.02	0.02	-9999	-10000	0	0
KSR1	0.012	0.011	-9999	-10000	0	0
MAPK8	0.01	0.027	-9999	-0.18	5	5
TRAF2	0.01	0	-9999	-10000	0	0
response to radiation	0	0	-9999	-10000	0	0
CHUK	0.023	0.02	-9999	-10000	0	0
TNF R/SODD	0.015	0	-9999	-10000	0	0
TNF	0.005	0.046	-9999	-0.44	3	3
CYCS	0.012	0.009	-9999	-10000	0	0
IKBKG	0.023	0.02	-9999	-10000	0	0
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.02	0.02	-9999	-10000	0	0
RELA	0.01	0	-9999	-10000	0	0
RIPK1	0.01	0	-9999	-10000	0	0
AIFM1	0.012	0.009	-9999	-10000	0	0
TNF/TNF R/SODD	0.016	0.028	-9999	-0.26	3	3
TNFRSF1A	0.01	0	-9999	-10000	0	0
response to heat	0	0	-9999	-10000	0	0
CASP8	0.017	0.007	-9999	-10000	0	0
NSMAF	0.02	0.02	-9999	-10000	0	0
response to hydrogen peroxide	0	0	-9999	-0.001	3	3
BCL2	0.01	0	-9999	-10000	0	0

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
CDKN2A	0.001	0.002	-9999	-9999
TP53	0	0	-9999	-9999
Senescence	0	0	-9999	-9999
Apoptosis	0	0	-9999	-9999
Activated_Oncogenes	0	0	-9999	-9999
MDM2	0	0	-9999	-9999
MDM4	0.01	0	-9999	-9999

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.01	0	-9999	-10000	0	0
Rac1/GDP	0.008	0	-9999	-10000	0	0
DOCK1	0.01	0	-9999	-10000	0	0
ITGA4	0.01	0.001	-9999	-10000	0	0
RAC1	0.01	0	-9999	-10000	0	0
alpha4/beta7 Integrin	0.015	0.001	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin	0.02	0.001	-9999	-10000	0	0
alpha4/beta7 Integrin/Paxillin	0.019	0.001	-9999	-10000	0	0
lamellipodium assembly	0.021	0.001	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
PI3K	0.015	0	-9999	-10000	0	0
ARF6	0.01	0	-9999	-10000	0	0
TLN1	0.01	0	-9999	-10000	0	0
PXN	0.009	0	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
ARF6/GTP	0.023	0.001	-9999	-10000	0	0
cell adhesion	0.024	0.001	-9999	-10000	0	0
CRKL/CBL	0.015	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.019	0.001	-9999	-10000	0	0
ITGB1	0.01	0	-9999	-10000	0	0
ITGB7	0.01	0	-9999	-10000	0	0
ARF6/GDP	0.008	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.021	0.016	-9999	-0.22	1	1
p130Cas/Crk/Dock1	0.02	0	-9999	-10000	0	0
VCAM1	0.007	0.026	-9999	-0.44	1	1
alpha4/beta1 Integrin/Paxillin/Talin	0.025	0.001	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.025	0.001	-9999	-10000	0	0
BCAR1	0.01	0	-9999	-10000	0	0
mol:GDP	-0.024	0.001	-9999	-10000	0	0
CBL	0.01	0	-9999	-10000	0	0
PRKACA	0.01	0	-9999	-10000	0	0
GIT1	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.025	0.001	-9999	-10000	0	0
Rac1/GTP	0.022	0.001	-9999	-10000	0	0

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.014	0.001	-9999	-10000	0	0
FBXW11	0.01	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.009	0.035	-9999	-0.26	5	5
NF kappa B1 p50/RelA/I kappa B alpha	0.022	0.012	-9999	-10000	0	0
NFKBIA	0.01	0.012	-9999	-0.19	1	1
MAPK14	0.01	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.014	0	-9999	-10000	0	0
ARRB2	0.008	0	-9999	-10000	0	0
REL	0.002	0.059	-9999	-0.44	5	5
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.014	0.001	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.014	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
NF kappa B1 p50 dimer	0.01	0	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
NFKB1	0.009	0	-9999	-10000	0	0
RELA	0.01	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.014	0.013	-9999	-0.18	1	1
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.023	0.012	-9999	-10000	0	0
SRC	0.01	0.001	-9999	-10000	0	0
PI3K	0.015	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.014	0.013	-9999	-0.18	1	1
IKBKB	0.01	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.01	0	-9999	-10000	0	0
SYK	0.008	0.026	-9999	-0.44	1	1
I kappa B alpha/PIK3R1	0.017	0.013	-9999	-0.18	1	1
cell death	0.022	0.011	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	0.009	0.035	-9999	-0.26	5	5
LCK	0.01	0.001	-9999	-10000	0	0
BCL3	0.01	0.001	-9999	-10000	0	0

×

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

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
BAG4	0.01	0	-10000	0	-10000	0	0
Caspase 8 (4 units)	0.021	0.008	-10000	0	-10000	0	0
NEF	0.002	0.001	-10000	0	-10000	0	0
NFKBIA	0.013	0.008	-10000	0	-10000	0	0
BIRC3	0.014	0.004	-10000	0	-10000	0	0
CYCS	0.027	0.029	-10000	0	-10000	0	0
RIPK1	0.01	0	-10000	0	-10000	0	0
CD247	0.01	0.004	-10000	0	-10000	0	0
MAP2K7	0.034	0.025	-10000	0	-10000	0	0
protein ubiquitination	0.031	0.023	-10000	0	-10000	0	0
CRADD	0.01	0	-10000	0	-10000	0	0
DAXX	0.01	0	-10000	0	-10000	0	0
FAS	0.01	0	-10000	0	-10000	0	0
BID	0.027	0.03	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha	0.024	0.006	-10000	0	-10000	0	0
TRADD	0.01	0	-10000	0	-10000	0	0
MAP3K5	0.01	0	-10000	0	-10000	0	0
CFLAR	0.01	0	-10000	0	-10000	0	0
FADD	0.01	0	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.024	0.006	-10000	0	-10000	0	0
MAPK8	0.031	0.034	-10000	0	-10000	0	0
APAF1	0.01	0	-10000	0	-10000	0	0
TRAF1	0.01	0.001	-10000	0	-10000	0	0
TRAF2	0.01	0	-10000	0	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.015	0.006	-10000	0	-10000	0	0
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.028	0.023	-10000	0	-10000	0	0
CHUK	0.031	0.024	-10000	0	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.029	0	-10000	0	-10000	0	0
TCRz/NEF	0.011	0.004	-10000	0	-10000	0	0
TNF	0.005	0.046	-10000	0	-0.44	3	3
FASLG	0.01	0.004	-10000	0	-10000	0	0
NFKB1	0.013	0.008	-10000	0	-10000	0	0
TNFR1A/BAG4/TNF-alpha	0.016	0.028	-10000	0	-0.26	3	3
CASP6	0.033	0.021	-10000	0	-10000	0	0
CASP7	0.047	0.041	0.25	3	-10000	0	3
RELA	0.013	0.008	-10000	0	-10000	0	0
CASP2	0.01	0	-10000	0	-10000	0	0
CASP3	0.047	0.041	0.25	3	-10000	0	3
TNFRSF1A	0.01	0	-10000	0	-10000	0	0
TNFR1A/BAG4	0.015	0	-10000	0	-10000	0	0
CASP8	0.01	0	-10000	0	-10000	0	0
CASP9	0.01	0	-10000	0	-10000	0	0
MAP3K14	0.032	0.025	-10000	0	-10000	0	0
APAF-1/Caspase 9	0.02	0.009	-10000	0	-10000	0	0
BCL2	0.031	0.032	-10000	0	-10000	0	0

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
MDK	0.007	0.004	-9999	-9999
GPC2	0.005	0.005	-9999	-9999
GPC2/Midkine	0.007	0.007	-9999	-9999
neuron projection morphogenesis	0.007	0.007	-9999	-9999

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.01	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.001	0.011	-9999	-0.18	1	1
MDM2/SUMO1	0.018	0	-9999	-10000	0	0
HDAC4	0.008	0.026	-9999	-0.44	1	1
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
SUMO1	0.01	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.007	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.01	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.01	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.01	0	-9999	-10000	0	0
SUMO1/HDAC4	0.018	0.013	-9999	-0.2	1	1
SUMO1/HDAC1	0.018	0	-9999	-10000	0	0
RANGAP1	0.01	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	0.025	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.009	0	-9999	-10000	0	0
Ran/GTP	0.014	0	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.01	0	-9999	-10000	0	0
UBE2I	0.01	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.015	0	-9999	-10000	0	0
NPC	0.006	0	-9999	-10000	0	0
PIAS2	0.01	0	-9999	-10000	0	0
PIAS1	0.01	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

IL2 signaling events mediated by STAT5

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
GAB2	0.01	0.001	-9999	-9999
ELF1	0.013	0.004	-9999	-9999
CCNA2	0.008	0.003	-9999	-9999
PIK3CA	0.01	0.001	-9999	-9999
JAK3	0.008	0.004	-9999	-9999
PIK3R1	0.01	0.001	-9999	-9999
JAK1	0.01	0.001	-9999	-9999
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.039	0.019	-9999	-9999
SHC1	0.01	0.001	-9999	-9999
SP1	0.012	0.005	-9999	-9999
IL2RA	0.013	0.004	-9999	-9999
IL2RB	0.009	0.003	-9999	-9999
SOS1	0.01	0.001	-9999	-9999
IL2RG	0.01	0.002	-9999	-9999
G1/S transition of mitotic cell cycle	0.041	0.034	-9999	-9999
PTPN11	0.01	0.001	-9999	-9999
CCND2	0.012	0.005	-9999	-9999
LCK	0.01	0.002	-9999	-9999
GRB2	0.01	0.001	-9999	-9999
IL2	0.004	0.005	-9999	-9999
CDK6	0.01	0	-9999	-9999
CCND3	0.048	0.031	-9999	-9999

×

Arf6 trafficking 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	0.007	0.037	-10000	0	-0.44	2	2
CLTC	0.014	0.005	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.011	0.001	-10000	0	-10000	0	0
Dynamin 2/GTP	0.013	0.001	-10000	0	-10000	0	0
EXOC4	0.01	0	-10000	0	-10000	0	0
CD59	0.012	0.003	-10000	0	-10000	0	0
CPE	0.008	0.001	-10000	0	-10000	0	0
CTNNB1	0.01	0	-10000	0	-10000	0	0
membrane fusion	0.01	0	-10000	0	-10000	0	0
CTNND1	0.012	0.007	-10000	0	-10000	0	0
DNM2	0.01	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.012	0.002	-10000	0	-10000	0	0
TSHR	0.007	0.002	-10000	0	-10000	0	0
INS	0.005	0.001	-10000	0	-10000	0	0
BIN1	0.007	0.037	-10000	0	-0.44	2	2
mol:Choline	0.01	0	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.008	0.001	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.01	0	-10000	0	-10000	0	0
mol:Ca2+	0.013	0.001	-10000	0	-10000	0	0
JUP	0.012	0.003	-10000	0	-10000	0	0
ASAP2/amphiphysin II	0.016	0.026	-10000	0	-0.23	3	3
ARF6/GTP	0.007	0	-10000	0	-10000	0	0
CDH1	-0.004	0.051	-10000	0	-10000	0	0
clathrin-independent pinocytosis	0.007	0	-10000	0	-10000	0	0
MAPK8IP3	0.01	0.001	-10000	0	-10000	0	0
positive regulation of endocytosis	0.007	0	-10000	0	-10000	0	0
EXOC2	0.01	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.018	0	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.01	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.009	0.039	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.008	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.013	0.002	-10000	0	-10000	0	0
ACAP1	0.01	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.01	0.003	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.013	0.007	-10000	0	-10000	0	0
JIP4/KLC1	0.019	0	-10000	0	-10000	0	0
EXOC1	0.01	0	-10000	0	-10000	0	0
exocyst	0.019	0	-10000	0	-10000	0	0
RALA/GTP	0.007	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.013	0	-10000	0	-10000	0	0
receptor recycling	0.007	0	-10000	0	-10000	0	0
CTNNA1	0.012	0.007	-10000	0	-10000	0	0
NME1	0.008	0.001	-10000	0	-10000	0	0
clathrin coat assembly	0.014	0.005	-10000	0	-10000	0	0
IL2RA	0.011	0.005	-10000	0	-10000	0	0
VAMP3	0.008	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	0.017	0.017	-10000	0	-10000	0	0
EXOC6	0.01	0	-10000	0	-10000	0	0
PLD1	0.009	0	-10000	0	-10000	0	0
PLD2	0.009	0	-10000	0	-10000	0	0
EXOC5	0.01	0	-10000	0	-10000	0	0
PIP5K1C	0.012	0.002	-10000	0	-10000	0	0
SDC1	0.011	0.011	-10000	0	-10000	0	0
ARF6/GDP	0.011	0.001	-10000	0	-10000	0	0
EXOC7	0.01	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.01	0.04	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.01	0	-10000	0	-10000	0	0
endocytosis	-0.016	0.025	0.23	3	-10000	0	3
SCAMP2	0.01	0	-10000	0	-10000	0	0
ADRB2	0.019	0.016	-10000	0	-10000	0	0
EXOC3	0.01	0	-10000	0	-10000	0	0
ASAP2	0.008	0.026	-10000	0	-0.44	1	1
Dynamin 2/GDP	0.014	0.001	-10000	0	-10000	0	0
KLC1	0.01	0	-10000	0	-10000	0	0
AVPR2	-0.16	0.082	-10000	0	-10000	0	0
RALA	0.01	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.011	0.038	-10000	0	-10000	0	0

×

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	0.008	0.004	-9999	-10000	0	0
CDKN2C	-0.009	0.01	-9999	-10000	0	0
CDKN2A	0.002	0.004	-9999	-10000	0	0
CCND2	-0.001	0.002	-9999	-10000	0	0
RB1	0.033	0.022	-9999	-10000	0	0
CDK4	-0.001	0.002	-9999	-10000	0	0
CDK6	-0.001	0.002	-9999	-10000	0	0
G1/S progression	-0.035	0.024	-9999	-0.1	5	5

×

Rapid glucocorticoid 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0.017	0.014	-10000	0	-0.22	1	1
MAPK9	0.004	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	0.002	0.002	-10000	0	-10000	0	0
GNB1/GNG2	0.013	0	-10000	0	-10000	0	0
GNB1	0.01	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.004	0	-10000	0	-10000	0	0
Gs family/GTP	0.005	0.014	-10000	0	-0.24	1	1
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	0.004	0.065	1	-10000	0	1
GNAL	0.008	0.026	-10000	0	-0.44	1	1
GNG2	0.01	0	-10000	0	-10000	0	0
CRH	0.004	0.005	-10000	0	-10000	0	0
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	-0.001	0.039	-10000	0	-0.3	5	5
MAPK11	0.004	0	-10000	0	-10000	0	0

×

p38 MAPK signaling 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.009	0	-9999	-10000	0	0
TRAF2/ASK1	0.013	0	-9999	-10000	0	0
ATM	0.01	0	-9999	-10000	0	0
MAP2K3	0.018	0.011	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.02	0.011	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
GADD45G	0.007	0.037	-9999	-0.44	2	2
TXN	0.004	0	-9999	-10000	0	0
CALM1	0.01	0	-9999	-10000	0	0
GADD45A	0.01	0	-9999	-10000	0	0
GADD45B	0.008	0.026	-9999	-0.44	1	1
MAP3K1	0.01	0	-9999	-10000	0	0
MAP3K6	0.01	0	-9999	-10000	0	0
MAP3K7	0.01	0	-9999	-10000	0	0
MAP3K4	0.01	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
ASK1/ASK2	0.015	0	-9999	-10000	0	0
TAK1/TAB family	-0.001	0	-9999	-10000	0	0
RAC1/OSM/MEKK3	0.019	0	-9999	-10000	0	0
TRAF2	0.01	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.023	0.009	-9999	-10000	0	0
TRAF6	0.004	0	-9999	-10000	0	0
RAC1	0.01	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
CAMK2B	0.002	0.052	-9999	-0.44	4	4
CCM2	0.01	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB	0.008	0.032	-9999	-0.26	4	4
MAPK11	0.01	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.013	0.03	-9999	-0.23	4	4
OSM/MEKK3	0.015	0	-9999	-10000	0	0
TAOK1	0.007	0.018	-9999	-0.29	1	1
TAOK2	0.008	0	-9999	-10000	0	0
TAOK3	0.008	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.01	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
MAP3K5	0.01	0	-9999	-10000	0	0
MAP3K10	0.01	0	-9999	-10000	0	0
MAP3K3	0.01	0	-9999	-10000	0	0
TRX/ASK1	0.01	0.001	-9999	-10000	0	0
GADD45/MTK1/MTK1	0.021	0.024	-9999	-0.22	3	3

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
coatomer protein complex	0.008	0	-9999	-9999
EntrezGene:79658	0	0	-9999	-9999
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.009	0	-9999	-9999
AP2	0.015	0	-9999	-9999
mol:DAG	0	0	-9999	-9999
Arfaptin 2/Rac/GTP	0.014	0	-9999	-9999
CLTB	0.01	0	-9999	-9999
coatomer protein complex/ARF1/GTP/ER cargo protein	0.011	0	-9999	-9999
CD4	0.009	0.002	-9999	-9999
CLTA	0.01	0	-9999	-9999
mol:GTP	0	0	-9999	-9999
ARFGAP1	0.005	0	-9999	-9999
mol:PI-4-5-P2	0.005	0	-9999	-9999
ARF1/GTP	0.012	0	-9999	-9999
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.01	0	-9999	-9999
mol:Choline	0.005	0	-9999	-9999
mol:GDP	0	0	-9999	-9999
ARF1	0.01	0	-9999	-9999
DDEF1	0.005	0	-9999	-9999
ARF1/GDP	0.004	0	-9999	-9999
AP2M1	0.01	0	-9999	-9999
EntrezGene:1313	0	0	-9999	-9999
actin filament polymerization	0.007	0	-9999	-9999
Rac/GTP	0.008	0	-9999	-9999
ARF1/GTP/GGA3/ARF-GAP1	0.016	0	-9999	-9999
ARFIP2	0.009	0	-9999	-9999
COPA	0.01	0	-9999	-9999
RAC1	0.01	0	-9999	-9999
ARF1/GTP/coatomer protein complex	0.01	0	-9999	-9999
ARF1/GTP/ARHGAP10	0.007	0	-9999	-9999
GGA3	0.01	0	-9999	-9999
ARF1/GTP/Membrin	0.011	0	-9999	-9999
AP2A1	0.01	0	-9999	-9999
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.011	0	-9999	-9999
ARF1/GDP/Membrin	0.011	0	-9999	-9999
Arfaptin 2/Rac/GDP	0.013	0	-9999	-9999
CYTH2	0.01	0	-9999	-9999
ARF1/GTP/GGA3	0.014	0	-9999	-9999
mol:ATP	0	0	-9999	-9999
Rac/GDP	0.007	0	-9999	-9999
mol:Brefeldin A	0	0	-9999	-9999
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.014	0.003	-9999	-9999
PLD2	0.005	0	-9999	-9999
ARF-GAP1/v-SNARE	0.005	0	-9999	-9999
PIP5K1A	0.005	0	-9999	-9999
ARF1/GTP/Membrin/GBF1/p115	0.011	0	-9999	-9999
mol:Phosphatic acid	0	0	-9999	-9999
mol:Phosphatidic acid	0.005	0	-9999	-9999
KDEL Receptor/Ligand/ARF-GAP1	0.005	0	-9999	-9999
GOSR2	0.007	0	-9999	-9999
USO1	0.007	0	-9999	-9999
GBF1	0.007	0	-9999	-9999
ARF1/GTP/Arfaptin 2	0.014	0	-9999	-9999
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.019	0.004	-9999	-9999

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
IKK alpha homodimer	0.015	-9999	-9999
FBXW11	0.01	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	0	-9999	-9999
beta TrCP1/SCF ubiquitin ligase complex	0.01	-9999	-9999
CHUK	0.01	-9999	-9999
NF kappa B2 p100/RelB	0.029	-9999	-9999
NFKB1	0.01	-9999	-9999
MAP3K14	0.01	-9999	-9999
NF kappa B1 p50/RelB	0.015	-9999	-9999
RELB	0.01	-9999	-9999
NFKB2	0.01	-9999	-9999
NF kappa B2 p52/RelB	0.013	-9999	-9999
regulation of B cell activation	0.013	-9999	-9999

pid_entity	TCGA.Y8.A8S1	TCGA.Y8.A8S0	TCGA.Y8.A8RZ	TCGA.Y8.A8RY
109_MAP3K5	0.038	0.021	0.021	0.021
47_PPARGC1A	0.0098	0.0098	0.0098	0.0098
105_BMP4	0.0098	0.0098	0.0098	0.0098
105_BMP6	0.0098	0.0098	0.0098	0.0098
105_BMP7	0.0098	0.0098	-0.44	0.0098
105_BMP2	0.0098	0.0098	0.0098	0.0098
131_RELN/VLDLR	0.025	0	0.025	0
30_TGFB1/TGF beta receptor Type II	0.0097	0.0097	0.0097	0.0097
84_STAT5B	-0.042	-0.14	-0.13	-0.14
84_STAT5A	-0.042	-0.14	-0.13	-0.14