PARADIGM pathway analysis of mRNASeq expression data - Lung Squamous Cell Carcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
Signaling events mediated by the Hedgehog family	169
Angiopoietin receptor Tie2-mediated signaling	157
Aurora B signaling	125
FOXM1 transcription factor network	116
Endothelins	84
TCGA08_retinoblastoma	64
Glypican 2 network	61
amb2 Integrin signaling	60
Thromboxane A2 receptor signaling	54
Fc-epsilon receptor I signaling in mast cells	53

Pathway.Name	Significance.Ratio	Avg.Num.Perturbations	Total.Perturbations	Num.Entities	Min.Mean.Truth	Max.Mean.Truth	Min.Mean.Within	Max.Mean.Within	Min.Mean.Any	Max.Mean.Within.1
Signaling events mediated by the Hedgehog family	0.3373	169	8830	52	-0.64	0.34	1000	-1000	-0.092	-1000
Angiopoietin receptor Tie2-mediated signaling	0.3134	157	13822	88	-0.75	0.06	1000	-1000	-0.13	-1000
Aurora B signaling	0.2495	125	8435	67	-0.62	0.005	1000	-1000	-0.085	-1000
FOXM1 transcription factor network	0.2315	116	5936	51	-0.71	0.002	1000	-1000	-0.2	-1000
Endothelins	0.1677	84	8133	96	-0.44	0.036	1000	-1000	-0.097	-1000
TCGA08_retinoblastoma	0.1277	64	516	8	-0.28	0.087	1000	-1000	-0.031	-1000
Glypican 2 network	0.1218	61	247	4	-0.085	-0.068	1000	-1000	-0.036	-1000
amb2 Integrin signaling	0.1198	60	4946	82	-0.68	0	1000	-1000	-0.1	-1000
Thromboxane A2 receptor signaling	0.1078	54	5731	105	-0.18	0.041	1000	-1000	-0.095	-1000
Fc-epsilon receptor I signaling in mast cells	0.1058	53	5171	97	-0.26	0.033	1000	-1000	-0.12	-1000
Aurora C signaling	0.1018	51	363	7	-0.41	0	1000	-1000	-0.051	-1000
IL4-mediated signaling events	0.0978	49	4538	91	-0.81	0.45	1000	-1000	-0.2	-1000
Signaling events regulated by Ret tyrosine kinase	0.0918	46	3777	82	-0.2	0	1000	-1000	-0.11	-1000
Glucocorticoid receptor regulatory network	0.0898	45	5170	114	-0.56	0.36	1000	-1000	-0.093	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0858	43	2238	52	-0.38	0.057	1000	-1000	-0.083	-1000
PLK1 signaling events	0.0838	42	3647	85	-0.38	0.072	1000	-1000	-0.062	-1000
Arf6 signaling events	0.0798	40	2490	62	-0.3	0.015	1000	-1000	-0.072	-1000
BMP receptor signaling	0.0798	40	3275	81	-0.39	0.037	1000	-1000	-0.11	-1000
Canonical Wnt signaling pathway	0.0778	39	2002	51	-0.47	0.16	1000	-1000	-0.071	-1000
Visual signal transduction: Cones	0.0758	38	1456	38	-0.29	0.009	1000	-1000	-0.081	-1000
Glypican 1 network	0.0758	38	1863	48	-0.22	0.032	1000	-1000	-0.059	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0758	38	2973	78	-0.13	0.036	1000	-1000	-0.094	-1000
Presenilin action in Notch and Wnt signaling	0.0699	35	2154	61	-0.47	0.016	1000	-1000	-0.087	-1000
Integrins in angiogenesis	0.0699	35	2954	84	-0.46	0.031	1000	-1000	-0.11	-1000
Nongenotropic Androgen signaling	0.0699	35	1857	52	-0.15	0.048	1000	-1000	-0.071	-1000
Nectin adhesion pathway	0.0679	34	2164	63	-0.27	0	1000	-1000	-0.09	-1000
TCGA08_p53	0.0679	34	242	7	-0.19	0.097	1000	-1000	-0.034	-1000
Calcium signaling in the CD4+ TCR pathway	0.0639	32	1007	31	-0.21	0.012	1000	-1000	-0.13	-1000
FOXA2 and FOXA3 transcription factor networks	0.0599	30	1418	46	-0.77	0.072	1000	-1000	-0.12	-1000
HIF-1-alpha transcription factor network	0.0579	29	2230	76	-0.44	0.017	1000	-1000	-0.22	-1000
Coregulation of Androgen receptor activity	0.0539	27	2092	76	-0.4	0.031	1000	-1000	-0.061	-1000
IL23-mediated signaling events	0.0539	27	1635	60	-0.24	0.018	1000	-1000	-0.19	-1000
LPA4-mediated signaling events	0.0519	26	323	12	-0.14	0.017	1000	-1000	-0.037	-1000
Syndecan-3-mediated signaling events	0.0519	26	938	35	-0.34	0	1000	-1000	-0.079	-1000
Reelin signaling pathway	0.0499	25	1412	56	-0.13	0.003	1000	-1000	-0.12	-1000
IL6-mediated signaling events	0.0499	25	1911	75	-0.48	0.05	1000	-1000	-0.12	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0499	25	1706	68	-0.23	0.015	1000	-1000	-0.15	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0459	23	2960	125	-0.2	0	1000	-1000	-0.12	-1000
ErbB4 signaling events	0.0439	22	1583	69	-0.38	0.2	1000	-1000	-0.1	-1000
Aurora A signaling	0.0439	22	1335	60	-0.49	0.028	1000	-1000	-0.075	-1000
Wnt signaling	0.0439	22	155	7	-0.094	0	1000	-1000	-0.059	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0439	22	2668	120	-0.27	0.13	1000	-1000	-0.093	-1000
Regulation of Androgen receptor activity	0.0439	22	1600	70	-0.42	0.018	1000	-1000	-0.082	-1000
Syndecan-1-mediated signaling events	0.0419	21	725	34	-0.36	0	1000	-1000	-0.087	-1000
Signaling mediated by p38-alpha and p38-beta	0.0419	21	957	44	-0.13	0	1000	-1000	-0.065	-1000
p75(NTR)-mediated signaling	0.0399	20	2514	125	-0.34	0	1000	-1000	-0.13	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0399	20	686	33	-0.27	0	1000	-1000	-0.071	-1000
IL12-mediated signaling events	0.0379	19	1704	87	-0.16	0.019	1000	-1000	-0.16	-1000
Osteopontin-mediated events	0.0379	19	728	38	-0.29	0	1000	-1000	-0.13	-1000
Plasma membrane estrogen receptor signaling	0.0379	19	1705	86	-0.18	0.031	1000	-1000	-0.098	-1000
Visual signal transduction: Rods	0.0379	19	999	52	-0.18	0	1000	-1000	-0.11	-1000
HIF-2-alpha transcription factor network	0.0339	17	753	43	-0.38	0.21	1000	-1000	-0.12	-1000
TCR signaling in naïve CD8+ T cells	0.0339	17	1599	93	-0.066	0.035	1000	-1000	-0.1	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0319	16	894	54	-0.15	0.02	1000	-1000	-0.12	-1000
PDGFR-alpha signaling pathway	0.0319	16	716	44	-0.2	0.021	1000	-1000	-0.074	-1000
Ephrin A reverse signaling	0.0279	14	100	7	-0.024	0.002	1000	-1000	-0.041	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0279	14	1273	85	-0.16	0.011	1000	-1000	-0.095	-1000
EGFR-dependent Endothelin signaling events	0.0259	13	276	21	-0.065	0	1000	-1000	-0.08	-1000
Noncanonical Wnt signaling pathway	0.0240	12	317	26	-0.1	0	1000	-1000	-0.098	-1000
Caspase cascade in apoptosis	0.0220	11	849	74	-0.071	0.035	1000	-1000	-0.071	-1000
Regulation of nuclear SMAD2/3 signaling	0.0220	11	1552	136	-0.34	0.094	1000	-1000	-0.11	-1000
Syndecan-2-mediated signaling events	0.0220	11	770	69	-0.17	0.031	1000	-1000	-0.073	-1000
Signaling events mediated by HDAC Class III	0.0220	11	443	40	-0.15	0.05	1000	-1000	-0.056	-1000
FAS signaling pathway (CD95)	0.0220	11	541	47	-0.19	0.009	1000	-1000	-0.058	-1000
Ras signaling in the CD4+ TCR pathway	0.0220	11	194	17	-0.057	0.008	1000	-1000	-0.074	-1000
JNK signaling in the CD4+ TCR pathway	0.0200	10	175	17	-0.044	0.022	1000	-1000	-0.08	-1000
S1P1 pathway	0.0200	10	378	36	-0.061	0.01	1000	-1000	-0.086	-1000
Effects of Botulinum toxin	0.0200	10	274	26	-0.071	0.005	1000	-1000	-0.07	-1000
BCR signaling pathway	0.0200	10	1080	99	-0.11	0.04	1000	-1000	-0.11	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0180	9	328	34	-0.029	0	1000	-1000	-0.072	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0180	9	734	74	-0.17	0.068	1000	-1000	-0.12	-1000
Syndecan-4-mediated signaling events	0.0180	9	623	67	-0.17	0.01	1000	-1000	-0.11	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0160	8	242	28	-0.18	0.02	1000	-1000	-0.065	-1000
Hedgehog signaling events mediated by Gli proteins	0.0160	8	583	65	-0.6	0.044	1000	-1000	-0.091	-1000
IL2 signaling events mediated by STAT5	0.0160	8	183	22	-0.15	0.06	1000	-1000	-0.071	-1000
S1P4 pathway	0.0160	8	220	25	-0.065	0.003	1000	-1000	-0.059	-1000
Signaling events mediated by PTP1B	0.0140	7	550	76	-0.1	0.033	1000	-1000	-0.1	-1000
TRAIL signaling pathway	0.0140	7	366	48	-0.096	0.046	1000	-1000	-0.083	-1000
Cellular roles of Anthrax toxin	0.0120	6	263	39	-0.092	0.017	1000	-1000	-0.042	-1000
Retinoic acid receptors-mediated signaling	0.0120	6	381	58	-0.22	0.034	1000	-1000	-0.092	-1000
Regulation of p38-alpha and p38-beta	0.0120	6	353	54	-0.087	0.036	1000	-1000	-0.086	-1000
LPA receptor mediated events	0.0120	6	635	102	-0.1	0.035	1000	-1000	-0.11	-1000
S1P3 pathway	0.0120	6	273	42	-0.18	0.041	1000	-1000	-0.065	-1000
Signaling events mediated by PRL	0.0120	6	209	34	-0.13	0.028	1000	-1000	-0.074	-1000
BARD1 signaling events	0.0100	5	304	57	-0.13	0.022	1000	-1000	-0.077	-1000
IL2 signaling events mediated by PI3K	0.0100	5	307	58	-0.23	0.074	1000	-1000	-0.099	-1000
IL27-mediated signaling events	0.0100	5	295	51	-0.12	0.011	1000	-1000	-0.11	-1000
IGF1 pathway	0.0100	5	326	57	-0.021	0.04	1000	-1000	-0.12	-1000
Insulin Pathway	0.0100	5	381	74	-0.1	0.032	1000	-1000	-0.12	-1000
ErbB2/ErbB3 signaling events	0.0080	4	274	65	-0.078	0.054	1000	-1000	-0.087	-1000
Signaling events mediated by HDAC Class II	0.0080	4	350	75	-0.081	0	1000	-1000	-0.076	-1000
a4b1 and a4b7 Integrin signaling	0.0080	4	20	5	-0.009	-0.001	1000	-1000	-0.041	-1000
IL1-mediated signaling events	0.0080	4	298	62	-0.061	0.042	1000	-1000	-0.13	-1000
Ephrin B reverse signaling	0.0080	4	215	48	-0.071	0.04	1000	-1000	-0.081	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0080	4	384	83	-0.069	0.05	1000	-1000	-0.096	-1000
EPHB forward signaling	0.0080	4	349	85	-0.072	0.033	1000	-1000	-0.11	-1000
Class I PI3K signaling events	0.0080	4	341	73	-0.054	0.026	1000	-1000	-0.076	-1000
Arf6 trafficking events	0.0080	4	301	71	-0.085	0.032	1000	-1000	-0.09	-1000
Regulation of Telomerase	0.0080	4	408	102	-0.12	0.025	1000	-1000	-0.12	-1000
p38 MAPK signaling pathway	0.0080	4	219	44	-0.069	0.034	1000	-1000	-0.073	-1000
IFN-gamma pathway	0.0060	3	244	68	-0.069	0.065	1000	-1000	-0.13	-1000
Signaling events mediated by HDAC Class I	0.0060	3	396	104	-0.081	0.041	1000	-1000	-0.088	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0060	3	139	45	-0.027	0.061	1000	-1000	-0.12	-1000
TCGA08_rtk_signaling	0.0060	3	90	26	-0.065	0.038	1000	-1000	-0.038	-1000
VEGFR1 specific signals	0.0060	3	212	56	-0.2	0.043	1000	-1000	-0.096	-1000
Circadian rhythm pathway	0.0040	2	59	22	-0.032	0.038	1000	-1000	-0.077	-1000
Ceramide signaling pathway	0.0040	2	159	76	-0.028	0.041	1000	-1000	-0.074	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0040	2	101	37	-0.012	0.025	1000	-1000	-0.093	-1000
PDGFR-beta signaling pathway	0.0040	2	224	97	-0.044	0.054	1000	-1000	-0.12	-1000
Class IB PI3K non-lipid kinase events	0.0040	2	6	3	-0.003	-1000	1000	-1000	-0.022	-1000
Insulin-mediated glucose transport	0.0020	1	52	32	-0.057	0.034	1000	-1000	-0.073	-1000
S1P5 pathway	0.0020	1	30	17	-0.01	0.006	1000	-1000	-0.059	-1000
FoxO family signaling	0.0020	1	97	64	-0.089	0.081	1000	-1000	-0.1	-1000
Signaling mediated by p38-gamma and p38-delta	0.0020	1	17	15	-0.001	0.027	1000	-1000	-0.057	-1000
Paxillin-dependent events mediated by a4b1	0.0020	1	43	36	-0.01	0.02	1000	-1000	-0.082	-1000
Rapid glucocorticoid signaling	0.0020	1	31	20	-0.007	0.007	1000	-1000	-0.047	-1000
E-cadherin signaling in keratinocytes	0.0020	1	62	43	-0.023	0.043	1000	-1000	-0.091	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	2	23	-0.001	0.036	1000	-1000	-0.086	-1000
Canonical NF-kappaB pathway	0.0000	0	33	39	-0.019	0.072	1000	-1000	-0.11	-1000
PLK2 and PLK4 events	0.0000	0	2	3	-0.001	0.019	1000	-1000	-0.03	-1000
Arf6 downstream pathway	0.0000	0	21	43	-0.024	0.025	1000	-1000	-0.046	-1000
EPO signaling pathway	0.0000	0	52	55	-0.007	0.066	1000	-1000	-0.12	-1000
mTOR signaling pathway	0.0000	0	14	53	-0.004	0.03	1000	-1000	-0.078	-1000
Class I PI3K signaling events mediated by Akt	0.0000	0	60	68	-0.057	0.043	1000	-1000	-0.086	-1000
ceramide signaling pathway	0.0000	0	47	49	-0.013	0.044	1000	-1000	-0.071	-1000
Atypical NF-kappaB pathway	0.0000	0	11	31	-0.001	0.03	1000	-1000	-0.083	-1000
E-cadherin signaling in the nascent adherens junction	0.0000	0	54	76	-0.026	0.053	1000	-1000	-0.11	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	1	27	-0.001	0.025	1000	-1000	-0.068	-1000
E-cadherin signaling events	0.0000	0	0	5	0	0	1000	-1000	-0.051	-1000
Arf1 pathway	0.0000	0	32	54	-0.022	0.022	1000	-1000	-0.062	-1000
Alternative NF-kappaB pathway	0.0000	0	4	13	-0.001	0	1000	-1000	-0.079	-1000
Total	NA	2623	165115	7203	-25	-990	131000	-131000	-12	-131000

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.43	0.29	-10000	0	-0.69	233	233
IHH	-0.47	0.38	-10000	0	-0.81	278	278
SHH Np/Cholesterol/GAS1	-0.069	0.16	-10000	0	-0.45	72	72
LRPAP1	0	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.068	0.16	0.45	72	-10000	0	72
SMO/beta Arrestin2	-0.36	0.25	-10000	0	-0.59	240	240
SMO	-0.38	0.27	-10000	0	-0.6	282	282
AKT1	-0.15	0.11	-10000	0	-10000	0	0
ARRB2	0	0	-10000	0	-10000	0	0
BOC	-0.004	0.049	-10000	0	-0.63	3	3
ADRBK1	0	0	-10000	0	-10000	0	0
heart looping	-0.37	0.26	-10000	0	-0.59	283	283
STIL	-0.32	0.24	-10000	0	-0.52	258	258
DHH N/PTCH2	-0.046	0.16	-10000	0	-0.56	41	41
DHH N/PTCH1	-0.36	0.24	-10000	0	-0.57	246	246
PIK3CA	0	0	-10000	0	-10000	0	0
DHH	-0.053	0.19	-10000	0	-0.74	36	36
PTHLH	-0.58	0.36	-10000	0	-0.92	233	233
determination of left/right symmetry	-0.37	0.26	-10000	0	-0.59	283	283
PIK3R1	0	0	-10000	0	-10000	0	0
skeletal system development	-0.58	0.35	-10000	0	-0.91	233	233
IHH N/Hhip	-0.64	0.38	-10000	0	-0.81	396	396
DHH N/Hhip	-0.4	0.3	-10000	0	-0.59	339	339
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.37	0.26	-10000	0	-0.59	283	283
pancreas development	-0.48	0.35	-10000	0	-0.74	330	330
HHAT	0	0	-10000	0	-10000	0	0
PI3K	0	0	-10000	0	-10000	0	0
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.013	0.098	-10000	0	-0.74	9	9
somite specification	-0.37	0.26	-10000	0	-0.59	283	283
SHH Np/Cholesterol/PTCH1	-0.35	0.25	-10000	0	-0.55	256	256
SHH Np/Cholesterol/PTCH2	-0.066	0.16	-10000	0	-0.43	77	77
SHH Np/Cholesterol/Megalin	-0.28	0.26	-10000	0	-0.49	284	284
SHH	-0.062	0.2	-10000	0	-0.54	72	72
catabolic process	-0.37	0.25	-10000	0	-0.57	288	288
SMO/Vitamin D3	-0.37	0.26	-10000	0	-0.59	255	255
SHH Np/Cholesterol/Hhip	-0.35	0.26	-10000	0	-0.5	351	351
LRP2	-0.37	0.37	-10000	0	-0.74	250	250
receptor-mediated endocytosis	-0.49	0.31	-10000	0	-0.71	289	289
SHH Np/Cholesterol/BOC	-0.063	0.15	-10000	0	-0.43	74	74
SHH Np/Cholesterol/CDO	-0.066	0.16	-10000	0	-0.43	77	77
mesenchymal cell differentiation	0.34	0.26	0.49	351	-10000	0	351
mol:Vitamin D3	-0.35	0.26	-10000	0	-0.56	256	256
IHH N/PTCH2	-0.3	0.27	-10000	0	-0.54	278	278
CDON	-0.007	0.073	-10000	0	-0.74	5	5
IHH N/PTCH1	-0.38	0.26	-10000	0	-0.58	288	288
Megalin/LRPAP1	-0.28	0.28	-10000	0	-0.56	250	250
PTCH2	-0.008	0.075	-10000	0	-0.68	6	6
SHH Np/Cholesterol	-0.062	0.15	-10000	0	-0.43	72	72
PTCH1	-0.37	0.25	-10000	0	-0.57	288	288
HHIP	-0.49	0.35	-10000	0	-0.74	330	330

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.51	0.54	-10000	0	-1	263	263
NCK1/PAK1/Dok-R	-0.24	0.23	-10000	0	-0.46	263	263
NCK1/Dok-R	-0.67	0.67	-10000	0	-1.3	263	263
PIK3CA	0.007	0.006	-10000	0	-10000	0	0
mol:beta2-estradiol	0.06	0.1	0.25	108	-10000	0	108
RELA	0	0	-10000	0	-10000	0	0
SHC1	0.003	0.005	-10000	0	-10000	0	0
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	0.05	0.14	-10000	0	-0.57	10	10
TNIP2	0	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.59	0.58	-10000	0	-1.1	263	263
FN1	-0.019	0.12	-10000	0	-0.74	13	13
PLD2	-0.66	0.72	-10000	0	-1.3	263	263
PTPN11	0	0	-10000	0	-10000	0	0
GRB14	-0.044	0.17	-10000	0	-0.73	30	30
ELK1	-0.56	0.61	-10000	0	-1.1	263	263
GRB7	-0.005	0.051	-10000	0	-0.57	4	4
PAK1	-0.001	0.026	-10000	0	-0.57	1	1
Tie2/Ang1/alpha5/beta1 Integrin	-0.64	0.63	-10000	0	-1.2	263	263
CDKN1A	-0.34	0.36	-10000	0	-0.68	252	252
ITGA5	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.67	0.67	-10000	0	-1.3	263	263
CRK	0	0	-10000	0	-10000	0	0
mol:NO	-0.35	0.38	-10000	0	-0.71	263	263
PLG	-0.66	0.72	-10000	0	-1.3	263	263
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.49	0.49	-10000	0	-0.95	263	263
GRB2	0	0	-10000	0	-10000	0	0
PIK3R1	0.003	0.005	-10000	0	-10000	0	0
ANGPT2	-0.33	0.34	-10000	0	-0.74	173	173
BMX	-0.73	0.76	-10000	0	-1.4	263	263
ANGPT1	-0.37	0.62	-10000	0	-1.5	118	118
tube development	-0.4	0.41	-10000	0	-0.78	260	260
ANGPT4	-0.33	0.37	-10000	0	-0.74	222	222
response to hypoxia	-0.034	0.037	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.73	0.72	-10000	0	-1.4	263	263
alpha5/beta1 Integrin	0	0	-10000	0	-10000	0	0
FGF2	-0.015	0.12	-10000	0	-0.74	14	14
STAT5A (dimer)	-0.47	0.48	-10000	0	-0.92	252	252
mol:L-citrulline	-0.35	0.38	-10000	0	-0.71	263	263
AGTR1	-0.3	0.37	-10000	0	-0.74	205	205
MAPK14	-0.68	0.71	-10000	0	-1.3	263	263
Tie2/SHP2	-0.59	0.62	-10000	0	-1.2	229	229
TEK	-0.66	0.69	-10000	0	-1.4	229	229
RPS6KB1	-0.48	0.51	-10000	0	-0.96	263	263
Angiotensin II/AT1	-0.23	0.28	-10000	0	-0.56	205	205
Tie2/Ang1/GRB2	-0.71	0.72	-10000	0	-1.4	263	263
MAPK3	-0.58	0.63	-10000	0	-1.2	263	263
MAPK1	-0.58	0.63	-10000	0	-1.2	263	263
Tie2/Ang1/GRB7	-0.71	0.72	-10000	0	-1.4	263	263
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	-0.66	0.72	-10000	0	-1.3	263	263
PI3K	-0.61	0.64	-10000	0	-1.2	263	263
FES	-0.67	0.71	-10000	0	-1.3	263	263
Crk/Dok-R	-0.67	0.67	-10000	0	-1.3	263	263
Tie2/Ang1/ABIN2	-0.71	0.72	-10000	0	-1.4	263	263
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.44	0.47	-10000	0	-0.88	263	263
STAT5A	0.004	0.005	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.48	0.51	-10000	0	-0.96	263	263
Tie2/Ang2	-0.6	0.6	-10000	0	-1.2	256	256
Tie2/Ang1	-0.75	0.83	-10000	0	-1.5	263	263
FOXO1	-0.44	0.47	-10000	0	-0.89	263	263
ELF1	-0.032	0.052	-10000	0	-10000	0	0
ELF2	-0.67	0.73	-10000	0	-1.3	263	263
mol:Choline	-0.61	0.66	-10000	0	-1.2	263	263
cell migration	-0.13	0.12	-10000	0	-0.25	146	146
FYN	-0.47	0.48	-10000	0	-0.93	252	252
DOK2	-0.068	0.21	-10000	0	-0.74	46	46
negative regulation of cell cycle	-0.31	0.32	-10000	0	-0.62	252	252
ETS1	-0.061	0.15	-10000	0	-0.82	12	12
PXN	-0.38	0.41	-10000	0	-0.77	263	263
ITGB1	0	0	-10000	0	-10000	0	0
NOS3	-0.41	0.44	-10000	0	-0.83	263	263
RAC1	0	0	-10000	0	-10000	0	0
TNF	-0.062	0.16	-10000	0	-0.81	13	13
MAPKKK cascade	-0.61	0.66	-10000	0	-1.2	263	263
RASA1	0	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.7	0.74	-10000	0	-1.4	263	263
NCK1	0	0	-10000	0	-10000	0	0
vasculogenesis	-0.31	0.34	-10000	0	-0.63	263	263
mol:Phosphatidic acid	-0.61	0.66	-10000	0	-1.2	263	263
mol:Angiotensin II	0.001	0.001	-10000	0	-10000	0	0
mol:NADP	-0.35	0.38	-10000	0	-0.71	263	263
Rac1/GTP	-0.47	0.44	-10000	0	-0.88	263	263
MMP2	-0.66	0.72	-10000	0	-1.3	263	263

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.18	0.15	-9999	-0.4	85	85
STMN1	-0.29	0.19	-9999	-0.41	359	359
Aurora B/RasGAP/Survivin	-0.51	0.22	-9999	-0.64	338	338
Chromosomal passenger complex/Cul3 protein complex	-0.2	0.1	-9999	-0.33	124	124
BIRC5	-0.49	0.21	-9999	-0.58	426	426
DES	-0.56	0.38	-9999	-0.83	322	322
Aurora C/Aurora B/INCENP	-0.22	0.15	-9999	-0.69	2	2
Aurora B/TACC1	-0.25	0.16	-9999	-0.35	359	359
Aurora B/PP2A	-0.29	0.19	-9999	-0.41	359	359
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.059	0.044	-9999	-10000	0	0
mitotic metaphase/anaphase transition	-0.005	0.003	-9999	-10000	0	0
NDC80	-0.41	0.29	-9999	-0.56	374	374
Cul3 protein complex	-0.01	0.062	-9999	-0.37	14	14
KIF2C	-0.17	0.087	-9999	-0.24	241	241
PEBP1	-0.002	0.048	-9999	-0.75	2	2
KIF20A	-0.3	0.29	-9999	-0.58	259	259
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.29	0.19	-9999	-0.41	359	359
SEPT1	-0.001	0.026	-9999	-0.57	1	1
SMC2	0	0	-9999	-10000	0	0
SMC4	0	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.11	0.067	-9999	-10000	0	0
PSMA3	0	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.004	-9999	-10000	0	0
H3F3B	-0.15	0.1	-9999	-10000	0	0
AURKB	-0.41	0.26	-9999	-0.58	359	359
AURKC	-0.003	0.042	-9999	-0.66	2	2
CDCA8	-0.15	0.26	-9999	-0.59	130	130
cytokinesis	-0.32	0.16	-9999	-0.49	176	176
Aurora B/Septin1	-0.3	0.16	-9999	-0.47	166	166
AURKA	-0.018	0.13	-9999	-0.58	24	24
INCENP	0.001	0.003	-9999	-10000	0	0
KLHL13	-0.013	0.084	-9999	-0.57	11	11
BUB1	-0.05	0.17	-9999	-0.58	47	47
hSgo1/Aurora B/Survivin	-0.62	0.31	-9999	-0.79	369	369
EVI5	0.005	0.004	-9999	-10000	0	0
RhoA/GTP	-0.27	0.18	-9999	-0.5	153	153
SGOL1	-0.3	0.29	-9999	-0.57	261	261
CENPA	-0.24	0.12	-9999	-0.31	342	342
NCAPG	-0.11	0.23	-9999	-0.57	98	98
Aurora B/HC8 Proteasome	-0.29	0.19	-9999	-0.41	359	359
NCAPD2	-0.001	0.026	-9999	-0.57	1	1
Aurora B/PP1-gamma	-0.29	0.19	-9999	-0.41	359	359
RHOA	0	0	-9999	-10000	0	0
NCAPH	-0.3	0.29	-9999	-0.57	257	257
NPM1	-0.14	0.084	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
KLHL9	-0.004	0.057	-9999	-0.74	3	3
mitotic prometaphase	-0.012	0.006	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.29	0.19	-9999	-0.4	359	359
PPP1CC	0	0	-9999	-10000	0	0
Centraspindlin	-0.3	0.2	-9999	-0.51	180	180
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.14	0.084	-9999	-10000	0	0
MYLK	-0.15	0.11	-9999	-0.61	3	3
KIF23	-0.11	0.23	-9999	-0.58	99	99
VIM	-0.3	0.21	-9999	-0.42	360	360
RACGAP1	0.001	0.003	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
NCL	-0.14	0.084	-9999	-10000	0	0
Chromosomal passenger complex	-0.27	0.15	-9999	-0.35	341	341
Chromosomal passenger complex/EVI5	-0.49	0.25	-9999	-0.63	350	350
TACC1	-0.003	0.046	-9999	-0.74	2	2
PPP2R5D	0	0	-9999	-10000	0	0
CUL3	0	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.58	0.44	-9999	-1	146	146
PLK1	-0.18	0.2	-9999	-10000	0	0
BIRC5	-0.33	0.16	-9999	-10000	0	0
HSPA1B	-0.58	0.44	-9999	-1	141	141
MAP2K1	-0.012	0.024	-9999	-10000	0	0
BRCA2	-0.58	0.44	-9999	-1	139	139
FOXM1	-0.71	0.56	-9999	-1.2	202	202
XRCC1	-0.58	0.44	-9999	-1	139	139
FOXM1B/p19	-0.6	0.44	-9999	-1	177	177
Cyclin D1/CDK4	-0.54	0.41	-9999	-1	118	118
CDC2	-0.61	0.46	-9999	-1.1	186	186
TGFA	-0.52	0.39	-9999	-0.95	117	117
SKP2	-0.58	0.44	-9999	-1	141	141
CCNE1	-0.13	0.24	-9999	-0.59	111	111
CKS1B	-0.58	0.44	-9999	-1.1	125	125
RB1	-0.26	0.16	-9999	-0.63	6	6
FOXM1C/SP1	-0.64	0.49	-9999	-1.1	178	178
AURKB	-0.28	0.19	-9999	-10000	0	0
CENPF	-0.64	0.48	-9999	-1.1	210	210
CDK4	0.002	0.028	-9999	-0.6	1	1
MYC	-0.51	0.39	-9999	-0.91	141	141
CHEK2	-0.012	0.024	-9999	-10000	0	0
ONECUT1	-0.57	0.44	-9999	-1	150	150
CDKN2A	-0.26	0.29	-9999	-0.57	233	233
LAMA4	-0.58	0.44	-9999	-1.1	147	147
FOXM1B/HNF6	-0.66	0.51	-9999	-1.2	150	150
FOS	-0.64	0.51	-9999	-1.2	155	155
SP1	0	0	-9999	-10000	0	0
CDC25B	-0.58	0.44	-9999	-1	146	146
response to radiation	-0.024	0.023	-9999	-10000	0	0
CENPB	-0.58	0.44	-9999	-1	140	140
CENPA	-0.7	0.47	-9999	-1.1	242	242
NEK2	-0.68	0.49	-9999	-1.1	233	233
HIST1H2BA	-0.58	0.44	-9999	-1.1	141	141
CCNA2	-0.15	0.26	-9999	-0.59	129	129
EP300	0	0	-9999	-10000	0	0
CCNB1/CDK1	-0.66	0.51	-9999	-1.2	163	163
CCNB2	-0.66	0.49	-9999	-1.1	218	218
CCNB1	-0.62	0.47	-9999	-1.1	154	154
ETV5	-0.58	0.44	-9999	-1.1	146	146
ESR1	-0.6	0.46	-9999	-1.1	151	151
CCND1	-0.55	0.42	-9999	-1	124	124
GSK3A	-0.004	0.019	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	-0.17	0.24	-9999	-0.44	197	197
CDK2	0.002	0.006	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.03	0.028	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.64	0.42	-9999	-1	215	215
GAS1	-0.58	0.45	-9999	-1.1	139	139
MMP2	-0.58	0.44	-9999	-1.1	137	137
RB1/FOXM1C	-0.58	0.45	-9999	-1.1	148	148
CREBBP	0	0	-9999	-10000	0	0

×

Endothelins

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
AKT1	-0.032	0.24	-9999	-0.6	56	56
PTK2B	0.003	0.005	-9999	-10000	0	0
mol:Ca2+	-0.086	0.3	-9999	-0.93	39	39
EDN1	-0.043	0.26	-9999	-0.79	44	44
EDN3	-0.086	0.23	-9999	-0.7	62	62
EDN2	-0.088	0.21	-9999	-0.59	74	74
HRAS/GDP	-0.19	0.31	-9999	-0.63	133	133
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.057	0.21	-9999	-0.49	65	65
ADCY4	-0.08	0.23	-9999	-0.58	65	65
ADCY5	-0.091	0.24	-9999	-0.56	77	77
ADCY6	-0.056	0.2	-9999	-0.62	36	36
ADCY7	-0.054	0.19	-9999	-0.59	39	39
ADCY1	-0.055	0.2	-9999	-0.59	38	38
ADCY2	-0.087	0.22	-9999	-0.58	56	56
ADCY3	-0.054	0.19	-9999	-0.61	36	36
ADCY8	-0.18	0.25	-9999	-0.55	95	95
ADCY9	-0.055	0.2	-9999	-0.58	41	41
arachidonic acid secretion	-0.15	0.28	-9999	-0.55	123	123
ETB receptor/Endothelin-1/Gq/GTP	-0.32	0.36	-9999	-0.62	232	232
GNAO1	-0.004	0.049	-9999	-0.63	3	3
HRAS	0.006	0.005	-9999	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	0.035	0.27	-9999	-0.56	56	56
ETA receptor/Endothelin-1/Gs/GTP	0.029	0.26	-9999	-0.54	58	58
mol:GTP	0	0.004	-9999	-10000	0	0
COL3A1	-0.047	0.26	-9999	-0.73	35	35
EDNRB	-0.44	0.36	-9999	-0.73	302	302
response to oxidative stress	0	0	-9999	-10000	0	0
CYSLTR2	-0.048	0.29	-9999	-0.8	43	43
CYSLTR1	-0.094	0.37	-9999	-0.87	78	78
SLC9A1	-0.008	0.13	-9999	-0.34	31	31
mol:GDP	-0.21	0.34	-9999	-0.69	136	136
SLC9A3	-0.37	0.4	-9999	-0.63	315	315
RAF1	-0.21	0.33	-9999	-0.66	148	148
JUN	-0.061	0.24	-9999	-0.67	35	35
JAK2	-0.032	0.24	-9999	-0.6	56	56
mol:IP3	-0.22	0.31	-9999	-0.66	139	139
ETA receptor/Endothelin-1	0.015	0.33	-9999	-0.69	56	56
PLCB1	0.002	0.033	-9999	-0.74	1	1
PLCB2	-0.005	0.094	-9999	-0.74	8	8
ETA receptor/Endothelin-3	-0.054	0.21	-9999	-0.54	68	68
FOS	-0.21	0.36	-9999	-0.87	90	90
Gai/GDP	-0.005	0.067	-9999	-0.95	1	1
CRK	0.003	0.005	-9999	-10000	0	0
mol:Ca ++	-0.26	0.38	-9999	-0.76	146	146
BCAR1	0.007	0.005	-9999	-10000	0	0
PRKCB1	-0.2	0.3	-9999	-0.62	141	141
GNAQ	0.008	0.034	-9999	-0.74	1	1
GNAZ	-0.009	0.08	-9999	-0.74	6	6
GNAL	-0.004	0.057	-9999	-0.74	3	3
Gs family/GDP	-0.21	0.27	-9999	-0.61	136	136
ETA receptor/Endothelin-1/Gq/GTP	-0.069	0.24	-9999	-0.55	69	69
MAPK14	-0.24	0.29	-9999	-0.65	139	139
TRPC6	-0.094	0.32	-9999	-1.1	36	36
GNAI2	0	0	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
GNAI1	-0.001	0.033	-9999	-0.74	1	1
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.26	0.31	-9999	-0.61	175	175
ETB receptor/Endothelin-2	-0.39	0.3	-9999	-0.59	333	333
ETB receptor/Endothelin-3	-0.39	0.31	-9999	-0.6	328	328
ETB receptor/Endothelin-1	-0.37	0.34	-9999	-0.61	315	315
MAPK3	-0.22	0.37	-9999	-0.77	124	124
MAPK1	-0.22	0.37	-9999	-0.8	113	113
Rac1/GDP	-0.18	0.31	-9999	-0.63	133	133
cAMP biosynthetic process	-0.079	0.21	-9999	-0.59	50	50
MAPK8	-0.085	0.28	-9999	-0.7	57	57
SRC	0	0	-9999	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.17	0.17	-9999	-0.41	88	88
p130Cas/CRK/Src/PYK2	-0.19	0.33	-9999	-0.67	135	135
mol:K +	0	0	-9999	-10000	0	0
G12/GDP	-0.18	0.31	-9999	-0.63	133	133
COL1A2	-0.26	0.32	-9999	-0.78	95	95
EntrezGene:2778	0	0	-9999	-10000	0	0
ETA receptor/Endothelin-2	-0.051	0.2	-9999	-0.46	78	78
mol:DAG	-0.22	0.31	-9999	-0.66	139	139
MAP2K2	-0.21	0.33	-9999	-0.65	150	150
MAP2K1	-0.21	0.33	-9999	-0.65	150	150
EDNRA	0.015	0.15	-9999	-0.93	6	6
positive regulation of muscle contraction	-0.033	0.21	-9999	-0.63	33	33
Gq family/GDP	-0.21	0.31	-9999	-0.69	126	126
HRAS/GTP	-0.22	0.33	-9999	-0.68	142	142
PRKCH	-0.2	0.3	-9999	-0.65	127	127
RAC1	0	0	-9999	-10000	0	0
PRKCA	-0.2	0.3	-9999	-0.66	128	128
PRKCB	-0.22	0.33	-9999	-0.7	136	136
PRKCE	-0.2	0.3	-9999	-0.65	127	127
PRKCD	-0.2	0.3	-9999	-0.65	127	127
PRKCG	-0.22	0.31	-9999	-0.66	140	140
regulation of vascular smooth muscle contraction	-0.25	0.43	-9999	-1	90	90
PRKCQ	-0.24	0.34	-9999	-0.71	145	145
PLA2G4A	-0.17	0.3	-9999	-0.61	123	123
GNA14	-0.17	0.32	-9999	-0.74	123	123
GNA15	0.008	0.006	-9999	-10000	0	0
GNA12	0	0	-9999	-10000	0	0
GNA11	0.008	0.006	-9999	-10000	0	0
Rac1/GTP	0.036	0.27	-9999	-0.56	56	56
MMP1	-0.23	0.24	-9999	-0.44	260	260

×

TCGA08_retinoblastoma

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
CDKN2B	-0.065	0.2	-10000	0	-0.71	46	46
CDKN2C	0.03	0.033	-10000	0	-10000	0	0
CDKN2A	-0.28	0.3	-10000	0	-0.6	233	233
CCND2	0.075	0.084	0.27	47	-10000	0	47
RB1	-0.082	0.087	-10000	0	-0.27	48	48
CDK4	0.087	0.09	0.27	47	-10000	0	47
CDK6	0.084	0.092	0.29	47	-10000	0	47
G1/S progression	0.075	0.094	0.27	48	-10000	0	48

×

Glypican 2 network

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
MDK	-0.01	0.076	-9999	-0.57	9	9
GPC2	-0.085	0.2	-9999	-0.57	74	74
GPC2/Midkine	-0.069	0.16	-9999	-0.42	82	82
neuron projection morphogenesis	-0.068	0.16	-9999	-0.42	82	82

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.063	0.22	-9999	-0.71	44	44
alphaM/beta2 Integrin/GPIbA	-0.064	0.21	-9999	-0.7	45	45
alphaM/beta2 Integrin/proMMP-9	-0.079	0.21	-9999	-0.67	46	46
PLAUR	0	0	-9999	-10000	0	0
HMGB1	0	0.002	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.059	0.2	-9999	-0.69	43	43
AGER	-0.68	0.21	-9999	-0.74	459	459
RAP1A	0	0	-9999	-10000	0	0
SELPLG	-0.05	0.18	-9999	-0.74	34	34
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.47	0.26	-9999	-0.52	459	459
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.032	0.13	-9999	-0.57	28	28
CYR61	-0.04	0.17	-9999	-0.74	27	27
TLN1	0	0	-9999	-10000	0	0
Rap1/GTP	-0.2	0.29	-9999	-0.63	116	116
RHOA	0	0	-9999	-10000	0	0
P-selectin oligomer	-0.19	0.32	-9999	-0.74	131	131
MYH2	-0.31	0.35	-9999	-0.7	175	175
MST1R	-0.047	0.18	-9999	-0.74	32	32
leukocyte activation during inflammatory response	-0.088	0.22	-9999	-0.58	67	67
APOB	-0.047	0.18	-9999	-0.72	33	33
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.006	0.066	-9999	-0.74	4	4
JAM3	-0.001	0.033	-9999	-0.74	1	1
GP1BA	-0.007	0.07	-9999	-0.7	5	5
alphaM/beta2 Integrin/CTGF	-0.077	0.25	-9999	-0.74	52	52
alphaM/beta2 Integrin	-0.26	0.37	-9999	-0.76	120	120
JAM3 homodimer	-0.001	0.033	-9999	-0.74	1	1
ICAM2	-0.051	0.19	-9999	-0.74	35	35
ICAM1	-0.06	0.2	-9999	-0.74	41	41
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.24	0.36	-9999	-0.74	120	120
cell adhesion	-0.063	0.21	-9999	-0.7	45	45
NFKB1	-0.46	0.31	-9999	-0.94	111	111
THY1	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.043	0.14	-9999	-0.45	48	48
alphaM/beta2 Integrin/LRP/tPA	-0.059	0.19	-9999	-0.64	43	43
IL6	-0.48	0.38	-9999	-1.1	112	112
ITGB2	-0.031	0.15	-9999	-0.74	21	21
elevation of cytosolic calcium ion concentration	-0.074	0.2	-9999	-0.64	43	43
alphaM/beta2 Integrin/JAM2/JAM3	-0.12	0.28	-9999	-0.64	97	97
JAM2	-0.12	0.27	-9999	-0.74	80	80
alphaM/beta2 Integrin/ICAM1	-0.11	0.28	-9999	-0.73	63	63
alphaM/beta2 Integrin/uPA/Plg	-0.078	0.2	-9999	-0.66	43	43
RhoA/GTP	-0.29	0.36	-9999	-0.86	117	117
positive regulation of phagocytosis	-0.18	0.27	-9999	-0.75	72	72
Ron/MSP	-0.036	0.14	-9999	-0.55	33	33
alphaM/beta2 Integrin/uPAR/uPA	-0.074	0.2	-9999	-0.65	43	43
alphaM/beta2 Integrin/uPAR	-0.059	0.2	-9999	-0.69	43	43
PLAU	-0.037	0.14	-9999	-0.57	32	32
PLAT	-0.007	0.063	-9999	-0.57	6	6
actin filament polymerization	-0.29	0.32	-9999	-0.65	175	175
MST1	-0.001	0.026	-9999	-0.57	1	1
alphaM/beta2 Integrin/lipoprotein(a)	-0.089	0.22	-9999	-0.59	67	67
TNF	-0.42	0.28	-9999	-0.85	111	111
RAP1B	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.081	0.22	-9999	-0.69	45	45
fibrinolysis	-0.078	0.2	-9999	-0.66	43	43
HCK	-0.009	0.08	-9999	-0.74	6	6
dendritic cell antigen processing and presentation	-0.24	0.36	-9999	-0.74	120	120
VTN	-0.28	0.36	-9999	-0.74	191	191
alphaM/beta2 Integrin/CYR61	-0.084	0.25	-9999	-0.74	57	57
LPA	-0.021	0.11	-9999	-0.57	18	18
LRP1	0	0	-9999	-10000	0	0
cell migration	-0.075	0.21	-9999	-0.66	44	44
FN1	-0.019	0.12	-9999	-0.74	13	13
alphaM/beta2 Integrin/Thy1	-0.059	0.2	-9999	-0.69	43	43
MPO	-0.035	0.16	-9999	-0.74	24	24
KNG1	-0.015	0.091	-9999	-0.57	13	13
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.25	0.34	-9999	-0.77	115	115
ELA2	0	0	-9999	-10000	0	0
PLG	-0.006	0.057	-9999	-0.57	5	5
CTGF	-0.029	0.14	-9999	-0.74	20	20
alphaM/beta2 Integrin/Hck	-0.065	0.22	-9999	-0.72	45	45
ITGAM	-0.063	0.21	-9999	-0.74	42	42
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.19	0.36	-9999	-0.66	146	146
HP	-0.22	0.34	-9999	-0.74	151	151
leukocyte adhesion	-0.44	0.31	-9999	-0.82	150	150
SELP	-0.19	0.32	-9999	-0.74	131	131

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	-0.061	0.21	-10000	0	-0.74	45	45
GNB1/GNG2	-0.071	0.09	-10000	0	-0.22	55	55
AKT1	-0.038	0.13	-10000	0	-0.22	40	40
EGF	-0.014	0.097	-10000	0	-0.69	10	10
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	-0.039	0.13	-10000	0	-0.6	18	18
mol:Ca2+	-0.078	0.18	-10000	0	-0.31	179	179
LYN	-0.016	0.076	-10000	0	-0.52	7	7
RhoA/GTP	-0.048	0.059	-10000	0	-10000	0	0
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.086	0.2	-10000	0	-0.35	174	174
GNG2	-0.007	0.073	-10000	0	-0.74	5	5
ARRB2	0	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.019	0.099	-10000	0	-0.54	5	5
G beta5/gamma2	-0.094	0.12	-10000	0	-0.29	72	72
PRKCH	-0.092	0.21	-10000	0	-0.36	163	163
DNM1	-0.002	0.036	-10000	0	-0.57	2	2
TXA2/TP beta/beta Arrestin3	-0.002	0.013	-10000	0	-10000	0	0
mol:GTP	0	0.002	-10000	0	-10000	0	0
PTGDR	-0.024	0.13	-10000	0	-0.74	16	16
G12 family/GTP	-0.12	0.14	-10000	0	-0.31	175	175
ADRBK1	0	0	-10000	0	-10000	0	0
ADRBK2	-0.001	0.033	-10000	0	-0.74	1	1
RhoA/GTP/ROCK1	0	0	-10000	0	-10000	0	0
mol:GDP	0.041	0.13	0.41	21	-10000	0	21
mol:NADP	-0.007	0.073	-10000	0	-0.74	5	5
RAB11A	0	0	-10000	0	-10000	0	0
PRKG1	-0.068	0.21	-10000	0	-0.74	46	46
mol:IP3	-0.1	0.22	-10000	0	-0.39	182	182
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	-0.16	0.3	-10000	0	-0.54	179	179
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.03	0.1	-10000	0	-0.64	7	7
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.019	0.088	-10000	0	-0.59	8	8
RHOA	0	0	-10000	0	-10000	0	0
PTGIR	-0.016	0.11	-10000	0	-0.74	11	11
PRKCB1	-0.1	0.22	-10000	0	-0.39	176	176
GNAQ	-0.001	0.033	-10000	0	-0.74	1	1
mol:L-citrulline	-0.007	0.073	-10000	0	-0.74	5	5
TXA2/TXA2-R family	-0.15	0.3	-10000	0	-0.55	175	175
LCK	-0.016	0.075	-10000	0	-0.52	7	7
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.018	0.089	-10000	0	-0.71	5	5
TXA2-R family/G12 family/GDP/G beta/gamma	0.019	0.042	-10000	0	-0.5	1	1
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.018	0.088	-10000	0	-0.71	5	5
MAPK14	-0.046	0.14	-10000	0	-0.25	46	46
TGM2/GTP	-0.13	0.26	-10000	0	-0.46	186	186
MAPK11	-0.046	0.14	-10000	0	-0.25	45	45
ARHGEF1	-0.037	0.11	-10000	0	-0.2	34	34
GNAI2	0	0	-10000	0	-10000	0	0
JNK cascade	-0.1	0.23	-10000	0	-0.4	175	175
RAB11/GDP	0	0	-10000	0	-10000	0	0
ICAM1	-0.078	0.19	-10000	0	-0.32	173	173
cAMP biosynthetic process	-0.099	0.21	-10000	0	-0.36	186	186
Gq family/GTP/EBP50	-0.037	0.11	-10000	0	-0.53	3	3
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	-0.015	0.071	-10000	0	-0.52	6	6
GNB5	0	0	-10000	0	-10000	0	0
GNB1	-0.001	0.033	-10000	0	-0.74	1	1
EGF/EGFR	0.023	0.097	-10000	0	-0.42	11	11
VCAM1	-0.072	0.17	-10000	0	-0.3	174	174
TP beta/Gq family/GDP/G beta5/gamma2	-0.019	0.099	-10000	0	-0.54	5	5
platelet activation	-0.064	0.19	-10000	0	-0.31	173	173
PGI2/IP	-0.012	0.083	-10000	0	-0.56	11	11
PRKACA	-0.02	0.1	-10000	0	-0.44	23	23
Gq family/GDP/G beta5/gamma2	-0.021	0.1	-10000	0	-0.56	5	5
TXA2/TP beta/beta Arrestin2	-0.002	0.011	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.006	0.11	-10000	0	-0.5	15	15
mol:DAG	-0.12	0.25	-10000	0	-0.44	176	176
EGFR	-0.023	0.12	-10000	0	-0.63	18	18
TXA2/TP alpha	-0.14	0.29	-10000	0	-0.5	186	186
Gq family/GTP	-0.068	0.12	-10000	0	-0.28	123	123
YES1	-0.015	0.071	-10000	0	-0.52	6	6
GNAI2/GTP	-0.017	0.084	-10000	0	-0.62	6	6
PGD2/DP	-0.018	0.099	-10000	0	-0.56	16	16
SLC9A3R1	-0.005	0.051	-10000	0	-0.57	4	4
FYN	-0.016	0.076	-10000	0	-0.56	6	6
mol:NO	-0.007	0.073	-10000	0	-0.74	5	5
GNA15	0	0	-10000	0	-10000	0	0
PGK/cGMP	-0.049	0.15	-10000	0	-0.51	48	48
RhoA/GDP	0	0	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.054	0.16	-10000	0	-0.73	19	19
NOS3	-0.007	0.073	-10000	0	-0.74	5	5
RAC1	0	0	-10000	0	-10000	0	0
PRKCA	-0.093	0.21	-10000	0	-0.37	164	164
PRKCB	-0.1	0.22	-10000	0	-0.39	176	176
PRKCE	-0.092	0.21	-10000	0	-0.37	162	162
PRKCD	-0.1	0.22	-10000	0	-0.39	172	172
PRKCG	-0.11	0.23	-10000	0	-0.41	175	175
muscle contraction	-0.14	0.28	-10000	0	-0.5	177	177
PRKCZ	-0.085	0.2	-10000	0	-0.35	174	174
ARR3	0	0	-10000	0	-10000	0	0
TXA2/TP beta	-0.02	0.095	-10000	0	-0.72	6	6
PRKCQ	-0.11	0.23	-10000	0	-0.4	180	180
MAPKKK cascade	-0.13	0.27	-10000	0	-0.48	177	177
SELE	-0.11	0.23	-10000	0	-0.42	173	173
TP beta/GNAI2/GDP/G beta/gamma	-0.022	0.099	-10000	0	-0.69	7	7
ROCK1	0	0	-10000	0	-10000	0	0
GNA14	-0.18	0.32	-10000	0	-0.74	123	123
chemotaxis	-0.18	0.34	-10000	0	-0.62	174	174
GNA12	0	0	-10000	0	-10000	0	0
GNA13	0	0	-10000	0	-10000	0	0
GNA11	0	0	-10000	0	-10000	0	0
Rac1/GTP	0	0	-10000	0	-10000	0	0

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0	0	-9999	-10000	0	0
LAT2	-0.16	0.25	-9999	-0.66	78	78
AP1	-0.2	0.27	-9999	-0.64	113	113
mol:PIP3	-0.16	0.29	-9999	-0.65	91	91
IKBKB	-0.072	0.16	-9999	-0.33	83	83
AKT1	-0.18	0.24	-9999	-0.67	72	72
IKBKG	-0.072	0.16	-9999	-0.34	82	82
MS4A2	-0.17	0.32	-9999	-0.74	118	118
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.006	0.005	-9999	-10000	0	0
MAP3K1	-0.1	0.23	-9999	-0.53	85	85
mol:Ca2+	-0.11	0.21	-9999	-0.46	91	91
LYN	0.005	0.049	-9999	-0.76	2	2
CBLB	-0.16	0.24	-9999	-0.64	76	76
SHC1	0.001	0.004	-9999	-10000	0	0
RasGAP/p62DOK	-0.052	0.14	-9999	-0.44	59	59
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	-0.001	0.033	-9999	-0.74	1	1
PLD2	-0.21	0.28	-9999	-0.75	76	76
PTPN13	-0.13	0.24	-9999	-0.6	76	76
PTPN11	0.005	0.011	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.083	0.19	-9999	-0.41	78	78
SYK	0.006	0.035	-9999	-0.77	1	1
GRB2	0	0	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.2	0.27	-9999	-0.69	91	91
LAT	-0.16	0.24	-9999	-0.64	76	76
PAK2	-0.13	0.26	-9999	-0.6	90	90
NFATC2	-0.18	0.32	-9999	-0.92	71	71
HRAS	-0.15	0.29	-9999	-0.68	92	92
GAB2	-0.021	0.12	-9999	-0.74	14	14
PLA2G1B	-0.002	0.037	-9999	-10000	0	0
Fc epsilon R1	-0.26	0.34	-9999	-0.63	205	205
Antigen/IgE/Fc epsilon R1	-0.24	0.32	-9999	-0.58	205	205
mol:GDP	-0.16	0.32	-9999	-0.74	92	92
JUN	0	0	-9999	-10000	0	0
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.006	0.005	-9999	-10000	0	0
FOS	-0.09	0.24	-9999	-0.74	61	61
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.17	0.26	-9999	-0.54	125	125
CHUK	-0.072	0.16	-9999	-0.34	82	82
KLRG1	-0.16	0.24	-9999	-0.63	77	77
VAV1	-0.16	0.25	-9999	-0.65	79	79
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.16	0.24	-9999	-0.64	76	76
negative regulation of mast cell degranulation	-0.14	0.22	-9999	-0.58	76	76
BTK	-0.21	0.33	-9999	-0.8	95	95
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.2	0.31	-9999	-0.88	70	70
GAB2/PI3K/SHP2	-0.2	0.27	-9999	-0.75	72	72
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.17	0.25	-9999	-0.67	78	78
RAF1	0.025	0.028	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.23	0.32	-9999	-0.82	77	77
FCER1G	-0.015	0.13	-9999	-0.75	14	14
FCER1A	-0.22	0.35	-9999	-0.75	148	148
Antigen/IgE/Fc epsilon R1/Fyn	-0.22	0.3	-9999	-0.55	205	205
MAPK3	0.033	0.023	-9999	-10000	0	0
MAPK1	0.033	0.023	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
MAPK8	-0.022	0.071	-9999	-10000	0	0
DUSP1	-0.087	0.24	-9999	-0.74	59	59
NF-kappa-B/RelA	-0.06	0.076	-9999	-10000	0	0
actin cytoskeleton reorganization	-0.14	0.25	-9999	-0.61	80	80
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.16	0.24	-9999	-0.62	85	85
FER	-0.16	0.24	-9999	-0.64	76	76
RELA	0	0	-9999	-10000	0	0
ITK	-0.078	0.18	-9999	-0.66	38	38
SOS1	0.001	0.004	-9999	-10000	0	0
PLCG1	-0.16	0.32	-9999	-0.73	92	92
cytokine secretion	-0.044	0.055	-9999	-10000	0	0
SPHK1	-0.16	0.24	-9999	-0.64	76	76
PTK2	-0.14	0.26	-9999	-0.65	78	78
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.21	0.29	-9999	-0.72	91	91
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.15	0.28	-9999	-0.63	91	91
MAP2K2	0.03	0.024	-9999	-10000	0	0
MAP2K1	0.03	0.024	-9999	-10000	0	0
MAP2K7	0	0	-9999	-10000	0	0
KLRG1/SHP2	-0.15	0.22	-9999	-0.58	77	77
MAP2K4	0.009	0.013	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.24	0.33	-9999	-0.59	206	206
mol:Choline	-0.2	0.28	-9999	-0.74	76	76
SHC/Grb2/SOS1	-0.15	0.22	-9999	-0.6	75	75
FYN	-0.001	0.033	-9999	-0.74	1	1
DOK1	0	0	-9999	-10000	0	0
PXN	-0.13	0.24	-9999	-0.59	76	76
HCLS1	-0.16	0.24	-9999	-0.62	80	80
PRKCB	-0.12	0.22	-9999	-0.48	92	92
FCGR2B	-0.013	0.098	-9999	-0.74	9	9
IGHE	-0.005	0.009	-9999	-10000	0	0
KLRG1/SHIP	-0.15	0.22	-9999	-0.6	76	76
LCP2	-0.009	0.081	-9999	-0.74	6	6
PLA2G4A	-0.16	0.24	-9999	-0.64	78	78
RASA1	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.2	0.28	-9999	-0.74	76	76
IKK complex	-0.04	0.12	-9999	-0.28	24	24
WIPF1	0	0	-9999	-10000	0	0

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.23	0.14	-9999	-0.68	2	2
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.064	0.041	-9999	-10000	0	0
AURKB	-0.41	0.26	-9999	-0.57	359	359
AURKC	-0.003	0.042	-9999	-0.66	2	2

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.4	0.54	-10000	0	-1.2	106	106
STAT6 (cleaved dimer)	-0.46	0.48	-10000	0	-1.1	134	134
IGHG1	-0.12	0.19	-10000	0	-0.41	2	2
IGHG3	-0.39	0.52	-10000	0	-1.1	122	122
AKT1	-0.14	0.26	-10000	0	-1	6	6
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.1	0.22	-10000	0	-1.1	6	6
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.16	0.27	-10000	0	-1	7	7
THY1	-0.4	0.54	-10000	0	-1.2	106	106
MYB	-0.02	0.11	-10000	0	-0.59	17	17
HMGA1	-0.005	0.051	-10000	0	-0.57	4	4
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.2	0.31	-10000	0	-0.68	51	51
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.16	0.27	-10000	0	-1.1	7	7
SP1	0.017	0.002	-10000	0	-10000	0	0
INPP5D	-0.001	0.033	-10000	0	-0.74	1	1
SOCS5	0.019	0.014	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.45	0.48	-10000	0	-1.2	115	115
SOCS1	-0.23	0.36	-10000	0	-0.78	68	68
SOCS3	-0.16	0.27	-10000	0	-1.1	6	6
FCER2	-0.34	0.5	-10000	0	-1.3	66	66
PARP14	0.008	0.005	-10000	0	-10000	0	0
CCL17	-0.47	0.62	-10000	0	-1.3	131	131
GRB2	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.12	0.22	-10000	0	-0.89	6	6
T cell proliferation	-0.39	0.55	-10000	0	-1.2	112	112
IL4R/JAK1	-0.4	0.54	-10000	0	-1.2	111	111
EGR2	-0.42	0.57	-10000	0	-1.3	115	115
JAK2	-0.004	0.034	-10000	0	-10000	0	0
JAK3	0.013	0.007	-10000	0	-10000	0	0
PIK3R1	0	0	-10000	0	-10000	0	0
JAK1	0.009	0.014	-10000	0	-10000	0	0
COL1A2	-0.1	0.18	-10000	0	-0.66	2	2
CCL26	-0.43	0.56	-10000	0	-1.2	121	121
IL4R	-0.42	0.58	-10000	0	-1.3	111	111
PTPN6	0.019	0.014	-10000	0	-10000	0	0
IL13RA2	-0.43	0.57	-10000	0	-1.3	116	116
IL13RA1	-0.004	0.034	-10000	0	-10000	0	0
IRF4	-0.17	0.36	-10000	0	-0.92	74	74
ARG1	-0.12	0.24	-10000	0	-0.84	28	28
CBL	-0.18	0.29	-10000	0	-0.74	22	22
GTF3A	0.013	0.013	-10000	0	-10000	0	0
PIK3CA	0	0	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.003	0.051	-10000	0	-10000	0	0
IRF4/BCL6	-0.18	0.31	-10000	0	-0.86	73	73
CD40LG	-0.11	0.28	-10000	0	-0.74	86	86
MAPK14	-0.18	0.29	-10000	0	-0.95	10	10
mitosis	-0.14	0.25	-10000	0	-0.91	6	6
STAT6	-0.47	0.64	-10000	0	-1.4	111	111
SPI1	-0.045	0.2	-10000	0	-0.74	37	37
RPS6KB1	-0.13	0.24	-10000	0	-0.87	6	6
STAT6 (dimer)	-0.47	0.64	-10000	0	-1.4	111	111
STAT6 (dimer)/PARP14	-0.43	0.58	-10000	0	-1.3	111	111
mast cell activation	0.008	0.015	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.17	0.29	-10000	0	-0.82	31	31
FRAP1	-0.14	0.26	-10000	0	-1	6	6
LTA	-0.4	0.54	-10000	0	-1.2	108	108
FES	-0.001	0.033	-10000	0	-0.74	1	1
T-helper 1 cell differentiation	0.45	0.62	1.4	111	-10000	0	111
CCL11	-0.4	0.53	-10000	0	-1.2	111	111
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.15	0.26	-10000	0	-1.1	7	7
IL2RG	0.002	0.087	-10000	0	-0.73	7	7
IL10	-0.4	0.55	-10000	0	-1.2	111	111
IRS1	0	0	-10000	0	-10000	0	0
IRS2	-0.004	0.057	-10000	0	-0.74	3	3
IL4	-0.079	0.14	-10000	0	-10000	0	0
IL5	-0.4	0.54	-10000	0	-1.2	106	106
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.31	0.42	-10000	0	-0.9	107	107
COL1A1	-0.14	0.23	-10000	0	-0.66	27	27
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.41	0.55	-10000	0	-1.3	106	106
IL2R gamma/JAK3	-0.001	0.066	-10000	0	-0.55	7	7
TFF3	-0.45	0.62	-10000	0	-1.4	118	118
ALOX15	-0.63	0.77	-10000	0	-1.5	188	188
MYBL1	-0.001	0.026	-10000	0	-0.57	1	1
T-helper 2 cell differentiation	-0.32	0.43	-10000	0	-0.92	112	112
SHC1	0	0	-10000	0	-10000	0	0
CEBPB	0.009	0.013	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.15	0.26	-10000	0	-0.99	8	8
mol:PI-3-4-5-P3	-0.14	0.26	-10000	0	-1	6	6
PI3K	-0.15	0.27	-10000	0	-1.1	6	6
DOK2	-0.068	0.21	-10000	0	-0.74	46	46
ETS1	0.001	0.11	-10000	0	-0.7	12	12
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.11	0.21	-10000	0	-0.86	6	6
ITGB3	-0.41	0.56	-10000	0	-1.3	108	108
PIGR	-0.81	0.83	-10000	0	-1.6	263	263
IGHE	0.029	0.044	-10000	0	-10000	0	0
MAPKKK cascade	-0.11	0.21	-10000	0	-0.84	6	6
BCL6	0.001	0.004	-10000	0	-10000	0	0
OPRM1	-0.4	0.54	-10000	0	-1.2	107	107
RETNLB	-0.4	0.54	-10000	0	-1.2	110	110
SELP	-0.58	0.75	-10000	0	-1.6	161	161
AICDA	-0.39	0.52	-10000	0	-1.2	107	107

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.044	0.055	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.099	0.14	-9999	-0.43	19	19
JUN	-0.063	0.14	-9999	-0.42	16	16
HRAS	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.17	0.22	-9999	-0.48	129	129
RAP1A	0	0	-9999	-10000	0	0
FRS2	0	0	-9999	-10000	0	0
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.17	0.22	-9999	-0.48	129	129
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.16	0.22	-9999	-0.48	125	125
RHOA	0	0	-9999	-10000	0	0
RAP1A/GTP	-0.15	0.2	-9999	-0.66	20	20
GRB7	-0.005	0.051	-9999	-0.57	4	4
RET51/GFRalpha1/GDNF	-0.17	0.22	-9999	-0.48	129	129
MAPKKK cascade	-0.13	0.17	-9999	-0.59	18	18
BCAR1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.16	0.22	-9999	-0.48	125	125
lamellipodium assembly	-0.095	0.13	-9999	-0.4	19	19
RET51/GFRalpha1/GDNF/SHC	-0.17	0.22	-9999	-0.48	129	129
PIK3CA	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.16	0.22	-9999	-0.48	125	125
RET9/GFRalpha1/GDNF/Shank3	-0.16	0.22	-9999	-0.48	125	125
MAPK3	-0.14	0.18	-9999	-0.62	20	20
DOK1	0	0	-9999	-10000	0	0
DOK6	-0.063	0.21	-9999	-0.74	43	43
PXN	0	0	-9999	-10000	0	0
neurite development	-0.14	0.18	-9999	-0.54	40	40
DOK5	-0.005	0.059	-9999	-0.66	4	4
GFRA1	-0.18	0.32	-9999	-0.74	125	125
MAPK8	-0.074	0.15	-9999	-0.44	16	16
HRAS/GTP	-0.14	0.19	-9999	-0.49	53	53
tube development	-0.15	0.2	-9999	-0.45	125	125
MAPK1	-0.14	0.18	-9999	-0.62	20	20
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.1	0.14	-9999	-0.33	125	125
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
PDLIM7	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.19	0.25	-9999	-0.62	72	72
SHC1	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.17	0.22	-9999	-0.48	129	129
RET51/GFRalpha1/GDNF/Dok5	-0.17	0.22	-9999	-0.49	129	129
PRKCA	-0.003	0.046	-9999	-0.74	2	2
HRAS/GDP	0	0	-9999	-10000	0	0
CREB1	-0.11	0.15	-9999	-0.36	125	125
PIK3R1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.1	0.14	-9999	-0.33	125	125
RET51/GFRalpha1/GDNF/Grb7	-0.17	0.22	-9999	-0.48	130	130
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.02	0.1	-9999	-0.57	17	17
DOK4	0	0	-9999	-10000	0	0
JNK cascade	-0.062	0.14	-9999	-0.41	16	16
RET9/GFRalpha1/GDNF/FRS2	-0.16	0.22	-9999	-0.48	125	125
SHANK3	-0.003	0.046	-9999	-0.74	2	2
RASA1	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.1	0.14	-9999	-0.33	125	125
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.1	0.14	-9999	-0.47	16	16
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.1	0.14	-9999	-0.47	16	16
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.1	0.14	-9999	-0.48	16	16
PI3K	-0.14	0.2	-9999	-0.65	19	19
SOS1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.15	0.2	-9999	-0.45	125	125
GRB10	0	0	-9999	-10000	0	0
activation of MAPKK activity	-0.1	0.14	-9999	-0.48	16	16
RET51/GFRalpha1/GDNF/FRS2	-0.17	0.22	-9999	-0.48	129	129
GAB1	0	0	-9999	-10000	0	0
IRS1	0	0	-9999	-10000	0	0
IRS2	-0.004	0.057	-9999	-0.74	3	3
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.1	0.14	-9999	-0.48	16	16
RET51/GFRalpha1/GDNF/PKC alpha	-0.17	0.22	-9999	-0.48	130	130
GRB2	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GDNF	-0.093	0.21	-9999	-0.57	81	81
RAC1	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.17	0.22	-9999	-0.48	129	129
Rac1/GTP	-0.11	0.16	-9999	-0.49	19	19
RET9/GFRalpha1/GDNF	-0.18	0.24	-9999	-0.46	191	191
GFRalpha1/GDNF	-0.2	0.27	-9999	-0.54	191	191

×

Glucocorticoid receptor regulatory 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
PCK2	0.059	0.098	-10000	0	-10000	0	0
SMARCC2	0.012	0	-10000	0	-10000	0	0
SMARCC1	0.012	0	-10000	0	-10000	0	0
TBX21	-0.2	0.35	-10000	0	-0.98	68	68
SUMO2	0.002	0.006	-10000	0	-10000	0	0
STAT1 (dimer)	0.017	0	-10000	0	-10000	0	0
FKBP4	-0.001	0.026	-10000	0	-0.57	1	1
FKBP5	0	0	-10000	0	-10000	0	0
GR alpha/HSP90/FKBP51/HSP90	0.13	0.1	0.34	39	-10000	0	39
PRL	-0.083	0.12	-10000	0	-0.63	1	1
cortisol/GR alpha (dimer)/TIF2	0.31	0.25	0.6	147	-10000	0	147
RELA	-0.046	0.1	-10000	0	-10000	0	0
FGG	-0.13	0.47	0.56	47	-0.62	228	275
GR beta/TIF2	0.14	0.12	0.37	49	-0.38	1	50
IFNG	-0.34	0.24	-10000	0	-0.8	56	56
apoptosis	0.026	0.12	0.46	2	-0.57	2	4
CREB1	0.001	0.028	-10000	0	-10000	0	0
histone acetylation	-0.011	0.15	0.31	4	-0.38	26	30
BGLAP	-0.094	0.14	-10000	0	-0.53	10	10
GR/PKAc	0.12	0.099	0.34	26	-10000	0	26
NF kappa B1 p50/RelA	-0.084	0.18	-10000	0	-0.49	36	36
SMARCD1	0.012	0	-10000	0	-10000	0	0
MDM2	0.11	0.097	0.29	56	-0.31	1	57
GATA3	-0.013	0.13	-10000	0	-0.71	17	17
AKT1	0	0	-10000	0	-10000	0	0
CSF2	-0.16	0.41	-10000	0	-1.3	52	52
GSK3B	0.002	0.006	-10000	0	-10000	0	0
NR1I3	0.045	0.11	0.47	1	-10000	0	1
CSN2	0.16	0.16	0.45	35	-10000	0	35
BRG1/BAF155/BAF170/BAF60A	0	0	-10000	0	-10000	0	0
NFATC1	0.001	0.034	-10000	0	-0.74	1	1
POU2F1	0.005	0.014	-10000	0	-10000	0	0
CDKN1A	0.025	0.024	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0	0.004	-10000	0	-10000	0	0
SFN	-0.057	0.17	-10000	0	-0.58	49	49
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.093	0.14	0.33	36	-10000	0	36
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	0.031	0.16	0.46	1	-0.9	11	12
JUN	-0.29	0.16	-10000	0	-0.55	74	74
IL4	-0.11	0.15	-10000	0	-0.59	6	6
CDK5R1	-0.01	0.081	-10000	0	-0.58	10	10
PRKACA	0	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.45	0.24	-10000	0	-0.61	256	256
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.13	0.099	0.34	27	-10000	0	27
cortisol/GR alpha (monomer)	0.36	0.32	0.73	159	-10000	0	159
NCOA2	-0.001	0.033	-10000	0	-0.74	1	1
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.18	0.25	-10000	0	-0.82	61	61
AP-1/NFAT1-c-4	-0.53	0.25	-10000	0	-0.75	193	193
AFP	-0.19	0.15	-10000	0	-0.71	10	10
SUV420H1	0	0	-10000	0	-10000	0	0
IRF1	0.18	0.15	0.49	38	-10000	0	38
TP53	0.028	0.034	-10000	0	-0.72	1	1
PPP5C	0	0	-10000	0	-10000	0	0
KRT17	-0.54	0.25	-10000	0	-0.68	320	320
KRT14	-0.37	0.23	-10000	0	-0.65	95	95
TBP	0.018	0	-10000	0	-10000	0	0
CREBBP	0.11	0.067	0.34	1	-10000	0	1
HDAC1	0	0.004	-10000	0	-10000	0	0
HDAC2	0.01	0.03	-10000	0	-10000	0	0
AP-1	-0.54	0.25	-10000	0	-0.75	198	198
MAPK14	0.002	0.005	-10000	0	-10000	0	0
MAPK10	-0.01	0.093	-10000	0	-0.74	8	8
MAPK11	0.002	0.006	-10000	0	-10000	0	0
KRT5	-0.56	0.26	-10000	0	-0.72	271	271
interleukin-1 receptor activity	0.007	0.028	-10000	0	-10000	0	0
NCOA1	0.013	0.001	-10000	0	-10000	0	0
STAT1	0.017	0	-10000	0	-10000	0	0
CGA	-0.12	0.17	-10000	0	-0.52	35	35
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.2	0.19	0.5	97	-10000	0	97
MAPK3	0.002	0.006	-10000	0	-10000	0	0
MAPK1	0.002	0.005	-10000	0	-10000	0	0
ICAM1	-0.26	0.43	-10000	0	-1.2	69	69
NFKB1	-0.046	0.1	-10000	0	-0.33	2	2
MAPK8	-0.24	0.17	-10000	0	-0.52	81	81
MAPK9	0.002	0.005	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.023	0.12	0.46	2	-0.6	2	4
BAX	0.025	0.024	-10000	0	-10000	0	0
POMC	-0.21	0.26	-10000	0	-0.95	21	21
EP300	0.11	0.068	0.34	1	-10000	0	1
cortisol/GR alpha (dimer)/p53	0.32	0.25	0.62	152	-10000	0	152
proteasomal ubiquitin-dependent protein catabolic process	0.075	0.074	0.27	10	-0.27	1	11
SGK1	0.17	0.077	-10000	0	-10000	0	0
IL13	-0.27	0.2	-10000	0	-0.89	24	24
IL6	-0.34	0.52	-10000	0	-1.3	103	103
PRKACG	-0.001	0.026	-10000	0	-0.57	1	1
IL5	-0.24	0.17	-10000	0	-0.8	19	19
IL2	-0.34	0.2	-10000	0	-0.75	49	49
CDK5	0.001	0.004	-10000	0	-10000	0	0
PRKACB	0	0	-10000	0	-10000	0	0
HSP90AA1	0	0	-10000	0	-10000	0	0
IL8	-0.2	0.28	-10000	0	-0.72	69	69
CDK5R1/CDK5	-0.006	0.059	-10000	0	-0.42	10	10
NF kappa B1 p50/RelA/PKAc	-0.058	0.13	-10000	0	-0.49	5	5
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.3	0.23	0.58	134	-10000	0	134
SMARCA4	0.012	0	-10000	0	-10000	0	0
chromatin remodeling	0.19	0.14	0.4	101	-10000	0	101
NF kappa B1 p50/RelA/Cbp	0.035	0.18	0.38	14	-0.52	4	18
JUN (dimer)	-0.29	0.16	-10000	0	-0.55	74	74
YWHAH	0	0	-10000	0	-10000	0	0
VIPR1	-0.41	0.51	-10000	0	-1	185	185
NR3C1	0.2	0.2	0.51	94	-10000	0	94
NR4A1	-0.096	0.26	-10000	0	-0.73	67	67
TIF2/SUV420H1	-0.001	0.025	-10000	0	-0.56	1	1
MAPKKK cascade	0.026	0.12	0.46	2	-0.57	2	4
cortisol/GR alpha (dimer)/Src-1	0.32	0.25	0.61	153	-10000	0	153
PBX1	0.002	0.049	-10000	0	-0.74	2	2
POU1F1	-0.002	0.046	-10000	0	-0.57	3	3
SELE	-0.47	0.61	-10000	0	-1.3	161	161
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.19	0.14	0.4	101	-10000	0	101
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.3	0.23	0.58	134	-10000	0	134
mol:cortisol	0.19	0.2	0.42	164	-0.24	3	167
MMP1	-0.33	0.19	-10000	0	-0.48	286	286

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.032	0.03	-9999	-10000	0	0
VDR	-0.001	0.033	-9999	-0.74	1	1
FAM120B	0	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.13	0.18	-9999	-0.54	10	10
RXRs/LXRs/DNA/Oxysterols	-0.097	0.16	-9999	-0.58	13	13
MED1	0	0	-9999	-10000	0	0
mol:9cRA	0.004	0.006	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	-0.013	0.061	-9999	-10000	0	0
RXRs/NUR77	-0.28	0.26	-9999	-0.48	289	289
RXRs/PPAR	-0.18	0.2	-9999	-0.56	43	43
NCOR2	-0.001	0.033	-9999	-0.74	1	1
VDR/VDR/Vit D3	-0.001	0.025	-9999	-0.56	1	1
RARs/VDR/DNA/Vit D3	-0.003	0.036	-9999	-0.41	4	4
RARA	0	0	-9999	-10000	0	0
NCOA1	0	0	-9999	-10000	0	0
VDR/VDR/DNA	-0.001	0.033	-9999	-0.74	1	1
RARs/RARs/DNA/9cRA	-0.002	0.032	-9999	-0.41	3	3
RARG	0	0	-9999	-10000	0	0
RPS6KB1	0.057	0.053	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	-0.013	0.063	-9999	-0.3	22	22
THRA	0	0	-9999	-10000	0	0
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	-0.001	0.025	-9999	-0.56	1	1
RXRs/PPAR/9cRA/PGJ2/DNA	-0.23	0.21	-9999	-0.43	265	265
NR1H4	-0.005	0.051	-9999	-0.57	4	4
RXRs/LXRs/DNA	-0.21	0.19	-9999	-0.56	10	10
NR1H2	0.015	0.004	-9999	-10000	0	0
NR1H3	0.014	0.005	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.21	0.2	-9999	-0.4	266	266
NR4A1	-0.096	0.25	-9999	-0.74	65	65
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.12	0.14	-9999	-0.33	11	11
RXRG	-0.38	0.37	-9999	-0.73	265	265
RXR alpha/CCPG	0	0	-9999	-10000	0	0
RXRA	0.015	0.004	-9999	-10000	0	0
RXRB	0.014	0.005	-9999	-10000	0	0
THRB	-0.026	0.14	-9999	-0.74	18	18
PPARG	-0.084	0.23	-9999	-0.74	57	57
PPARD	0	0	-9999	-10000	0	0
TNF	-0.1	0.23	-9999	-1.2	13	13
mol:Oxysterols	0.005	0.007	-9999	-10000	0	0
cholesterol transport	-0.097	0.16	-9999	-0.58	13	13
PPARA	0	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	-0.004	0.057	-9999	-0.74	3	3
RXRs/NUR77/BCL2	-0.2	0.19	-9999	-0.35	289	289
SREBF1	-0.082	0.15	-9999	-0.6	9	9
RXRs/RXRs/DNA/9cRA	-0.23	0.21	-9999	-0.43	265	265
ABCA1	-0.082	0.15	-9999	-0.6	9	9
RARs/THRs	-0.017	0.08	-9999	-0.4	21	21
RXRs/FXR	-0.23	0.22	-9999	-0.43	265	265
BCL2	-0.001	0.026	-9999	-0.57	1	1

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0.072	0.075	0.14	261	-10000	0	261
BUB1B	-0.13	0.1	-10000	0	-0.22	200	200
PLK1	-0.014	0.037	-10000	0	-0.13	10	10
PLK1S1	-0.003	0.02	-10000	0	-10000	0	0
KIF2A	-0.005	0.034	-10000	0	-10000	0	0
regulation of mitotic centrosome separation	-0.014	0.037	-10000	0	-0.13	10	10
GOLGA2	0	0	-10000	0	-10000	0	0
Hec1/SPC24	-0.2	0.23	-10000	0	-0.41	240	240
WEE1	-0.007	0.039	-10000	0	-10000	0	0
cytokinesis	-0.11	0.13	-10000	0	-0.29	47	47
PP2A-alpha B56	-0.008	0.023	-10000	0	-10000	0	0
AURKA	-0.007	0.03	-10000	0	-0.13	5	5
PICH/PLK1	-0.12	0.17	-10000	0	-0.46	59	59
CENPE	-0.039	0.11	-10000	0	-0.36	52	52
RhoA/GTP	0	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.005	0.033	-10000	0	-10000	0	0
PPP2CA	0	0	-10000	0	-10000	0	0
FZR1	0	0	-10000	0	-10000	0	0
TPX2	-0.061	0.049	-10000	0	-10000	0	0
PAK1	0.003	0.026	-10000	0	-0.57	1	1
SPC24	-0.16	0.26	-10000	0	-0.57	138	138
FBXW11	0	0	-10000	0	-10000	0	0
CLSPN	-0.012	0.038	-10000	0	-0.12	34	34
GORASP1	0	0	-10000	0	-10000	0	0
metaphase	-0.001	0.003	-10000	0	-0.011	25	25
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	-0.007	0.02	-10000	0	-0.067	5	5
G2 phase of mitotic cell cycle	0	0.002	-10000	0	-10000	0	0
STAG2	0	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.003	0.011	-10000	0	-10000	0	0
spindle elongation	-0.014	0.037	-10000	0	-0.13	10	10
ODF2	0.004	0.005	-10000	0	-10000	0	0
BUB1	-0.006	0.033	-10000	0	-10000	0	0
TPT1	-0.003	0.02	-10000	0	-10000	0	0
CDC25C	-0.078	0.058	-10000	0	-0.17	5	5
CDC25B	0.009	0.003	-10000	0	-10000	0	0
SGOL1	-0.072	0.075	-10000	0	-0.14	261	261
RHOA	0	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.031	0.082	-10000	0	-0.3	5	5
CDC14B	0.01	0.002	-10000	0	-10000	0	0
CDC20	-0.38	0.27	-10000	0	-0.57	331	331
PLK1/PBIP1	-0.028	0.059	-10000	0	-0.33	15	15
mitosis	-0.001	0.005	0.022	14	-10000	0	14
FBXO5	-0.004	0.032	-10000	0	-10000	0	0
CDC2	-0.001	0.004	-10000	0	-0.012	20	20
NDC80	-0.2	0.27	-10000	0	-0.57	175	175
metaphase plate congression	-0.007	0.026	-10000	0	-10000	0	0
ERCC6L	-0.12	0.17	-10000	0	-0.44	59	59
NLP/gamma Tubulin	-0.005	0.022	-10000	0	-10000	0	0
microtubule cytoskeleton organization	-0.003	0.02	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	0	0.001	-10000	0	-10000	0	0
PPP1R12A	0.003	0.005	-10000	0	-10000	0	0
interphase	0	0.001	-10000	0	-10000	0	0
PLK1/PRC1-2	-0.2	0.2	-10000	0	-0.4	183	183
GRASP65/GM130/RAB1/GTP/PLK1	-0.009	0.016	-10000	0	-10000	0	0
RAB1A	0	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	-0.001	0.029	-10000	0	-10000	0	0
mitotic prometaphase	-0.003	0.003	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.045	0.035	-10000	0	-10000	0	0
microtubule-based process	-0.18	0.17	-10000	0	-0.34	259	259
Golgi organization	-0.014	0.037	-10000	0	-0.13	10	10
Cohesin/SA2	-0.019	0.025	-10000	0	-10000	0	0
PPP1CB/MYPT1	0	0	-10000	0	-10000	0	0
KIF20A	-0.3	0.29	-10000	0	-0.57	259	259
APC/C/CDC20	-0.23	0.16	-10000	0	-0.34	331	331
PPP2R1A	0	0	-10000	0	-10000	0	0
chromosome segregation	-0.028	0.058	-10000	0	-0.32	15	15
PRC1	-0.055	0.17	-10000	0	-0.57	48	48
ECT2	-0.016	0.073	-10000	0	-0.35	18	18
C13orf34	-0.003	0.029	-10000	0	-10000	0	0
NUDC	-0.007	0.026	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.13	0.099	-10000	0	-0.22	200	200
spindle assembly	-0.009	0.03	-10000	0	-10000	0	0
spindle stabilization	-0.003	0.02	-10000	0	-10000	0	0
APC/C/HCDH1	0	0	-10000	0	-10000	0	0
MKLP2/PLK1	-0.18	0.17	-10000	0	-0.35	259	259
CCNB1	-0.063	0.19	-10000	0	-0.57	63	63
PPP1CB	0.003	0.005	-10000	0	-10000	0	0
BTRC	0	0	-10000	0	-10000	0	0
ROCK2	0.001	0.025	-10000	0	-10000	0	0
TUBG1	-0.003	0.02	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.033	0.079	-10000	0	-0.29	5	5
MLF1IP	-0.007	0.075	-10000	0	-0.43	15	15
INCENP	0.005	0.006	-10000	0	-10000	0	0

×

Arf6 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
CENTA1/KIF3B	-0.015	0.089	-9999	0	-0.51	15	15
ARNO/beta Arrestin1-2	-0.17	0.24	-9999	0	-0.7	50	50
EGFR	-0.023	0.12	-9999	0	-0.63	18	18
EPHA2	-0.004	0.057	-9999	0	-0.74	3	3
USP6	0	0	-9999	0	-10000	0	0
IQSEC1	0	0	-9999	0	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.027	0.12	-9999	0	-0.5	27	27
ARRB2	0.008	0.011	-9999	0	-0.22	1	1
mol:GTP	0.015	0.024	-9999	0	-0.15	7	7
ARRB1	-0.14	0.29	-9999	0	-0.74	98	98
FBXO8	0	0	-9999	0	-10000	0	0
TSHR	-0.017	0.098	-9999	0	-0.57	15	15
EGF	-0.014	0.097	-9999	0	-0.69	10	10
somatostatin receptor activity	0	0	-9999	0	-0.001	153	153
ARAP2	-0.001	0.033	-9999	0	-0.74	1	1
mol:GDP	-0.12	0.15	-9999	0	-0.33	140	140
mol:PI-3-4-5-P3	0	0	-9999	0	-0.001	92	92
ITGA2B	-0.022	0.13	-9999	0	-0.74	15	15
ARF6	0	0	-9999	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.003	0.033	-9999	0	-0.43	3	3
ADAP1	-0.012	0.092	-9999	0	-0.74	8	8
KIF13B	-0.012	0.092	-9999	0	-0.74	8	8
HGF/MET	-0.12	0.23	-9999	0	-0.56	111	111
PXN	0	0	-9999	0	-10000	0	0
ARF6/GTP	-0.12	0.15	-9999	0	-0.31	153	153
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.023	0.099	-9999	0	-0.42	27	27
ADRB2	-0.21	0.33	-9999	0	-0.74	143	143
receptor agonist activity	0	0	-9999	0	0	157	157
actin filament binding	0	0	-9999	0	-0.001	153	153
SRC	0	0	-9999	0	-10000	0	0
ITGB3	-0.016	0.11	-9999	0	-0.74	11	11
GNAQ	0	0.033	-9999	0	-0.74	1	1
EFA6/PI-4-5-P2	0	0.001	-9999	0	-0.001	128	128
ARF6/GDP	-0.013	0.07	-9999	0	-0.35	3	3
ARF6/GDP/GULP/ACAP1	-0.11	0.14	-9999	0	-0.42	46	46
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.022	0.096	-9999	0	-0.43	26	26
ACAP1	-0.003	0.042	-9999	0	-0.66	2	2
ACAP2	0	0	-9999	0	-10000	0	0
LHCGR/beta Arrestin2	-0.001	0.014	-9999	0	-0.32	1	1
EFNA1	0	0	-9999	0	-10000	0	0
HGF	-0.16	0.3	-9999	0	-0.74	108	108
CYTH3	0.01	0	-9999	0	-10000	0	0
CYTH2	0.005	0.002	-9999	0	-10000	0	0
NCK1	0	0	-9999	0	-10000	0	0
fibronectin binding	0	0	-9999	0	0	112	112
endosomal lumen acidification	0	0	0	1	-0.001	99	100
microtubule-based process	0	0	-9999	0	-10000	0	0
GULP1	-0.013	0.098	-9999	0	-0.74	9	9
GNAQ/ARNO	0.004	0.02	-9999	0	-0.41	1	1
mol:Phosphatidic acid	0	0	-9999	0	-10000	0	0
PIP3-E	0	0	-9999	0	0	11	11
MET	-0.004	0.053	-9999	0	-0.68	3	3
GNA14	-0.18	0.32	-9999	0	-0.74	123	123
GNA15	0	0	-9999	0	-10000	0	0
GIT1	0	0	-9999	0	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	0	-0.001	152	152
GNA11	0	0	-9999	0	-10000	0	0
LHCGR	-0.001	0.026	-9999	0	-0.57	1	1
AGTR1	-0.3	0.36	-9999	0	-0.74	205	205
desensitization of G-protein coupled receptor protein signaling pathway	-0.001	0.014	-9999	0	-0.32	1	1
IPCEF1/ARNO	-0.017	0.078	-9999	0	-0.41	12	12
alphaIIb/beta3 Integrin	-0.029	0.12	-9999	0	-0.56	26	26

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.18	0.21	-9999	-0.56	76	76
SMAD6-7/SMURF1	-0.047	0.14	-9999	-0.48	49	49
NOG	-0.031	0.15	-9999	-0.73	21	21
SMAD9	-0.1	0.21	-9999	-0.59	73	73
SMAD4	0	0	-9999	-10000	0	0
SMAD5	-0.022	0.13	-9999	-0.47	23	23
BMP7/USAG1	-0.24	0.27	-9999	-0.5	242	242
SMAD5/SKI	-0.049	0.11	-9999	-0.44	22	22
SMAD1	0.033	0.029	-9999	-10000	0	0
BMP2	-0.093	0.24	-9999	-0.74	63	63
SMAD1/SMAD1/SMAD4	-0.031	0.091	-9999	-10000	0	0
BMPR1A	0	0	-9999	-10000	0	0
BMPR1B	-0.056	0.2	-9999	-0.74	38	38
BMPR1A-1B/BAMBI	-0.04	0.13	-9999	-0.48	41	41
AHSG	-0.02	0.1	-9999	-0.57	17	17
CER1	-0.002	0.036	-9999	-0.57	2	2
BMP2-4/CER1	-0.073	0.18	-9999	-0.5	72	72
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.066	0.13	-9999	-0.49	29	29
BMP2-4 (homodimer)	-0.082	0.2	-9999	-0.57	72	72
RGMB	0	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.043	0.13	-9999	-0.45	48	48
RGMA	-0.065	0.18	-9999	-0.58	56	56
SMURF1	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.062	0.12	-9999	-0.44	29	29
BMP2-4/USAG1	-0.16	0.26	-9999	-0.54	147	147
SMAD6/SMURF1/SMAD5	-0.049	0.11	-9999	-0.44	22	22
SOSTDC1	-0.14	0.29	-9999	-0.74	95	95
BMP7/BMPR2/BMPR1A-1B	-0.14	0.19	-9999	-0.52	44	44
SKI	0	0	-9999	-10000	0	0
BMP6 (homodimer)	-0.018	0.11	-9999	-0.74	12	12
HFE2	-0.002	0.036	-9999	-0.57	2	2
ZFYVE16	0	0	-9999	-10000	0	0
MAP3K7	0	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.073	0.18	-9999	-0.5	72	72
SMAD5/SMAD5/SMAD4	-0.049	0.11	-9999	-0.44	22	22
MAPK1	0	0	-9999	-10000	0	0
TAK1/TAB family	-0.05	0.1	-9999	-0.45	16	16
BMP7 (homodimer)	-0.2	0.28	-9999	-0.58	170	170
NUP214	0	0	-9999	-10000	0	0
BMP6/FETUA	-0.027	0.11	-9999	-0.48	29	29
SMAD1/SKI	0.037	0.028	-9999	-10000	0	0
SMAD6	-0.072	0.22	-9999	-0.74	49	49
CTDSP2	0	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.083	0.19	-9999	-0.5	71	71
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.35	0.28	-9999	-0.57	303	303
BMPR2 (homodimer)	0	0	-9999	-10000	0	0
GADD34/PP1CA	0	0	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.042	0.15	-9999	-0.56	38	38
CHRDL1	-0.39	0.37	-9999	-0.74	263	263
ENDOFIN/SMAD1	0.037	0.028	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.036	0.1	-9999	-10000	0	0
SMAD6/SMURF1	0	0	-9999	-10000	0	0
BAMBI	-0.007	0.067	-9999	-0.67	5	5
SMURF2	0	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.32	0.3	-9999	-0.55	288	288
BMP2-4/GREM1	-0.28	0.22	-9999	-0.62	71	71
SMAD7	0	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.094	0.2	-9999	-0.55	73	73
SMAD1/SMAD6	0.037	0.028	-9999	-10000	0	0
TAK1/SMAD6	0	0	-9999	-10000	0	0
BMP7	-0.2	0.28	-9999	-0.58	170	170
BMP6	-0.018	0.11	-9999	-0.74	12	12
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.057	0.11	-9999	-0.4	29	29
PPM1A	0	0	-9999	-10000	0	0
SMAD1/SMURF2	0.037	0.028	-9999	-10000	0	0
SMAD7/SMURF1	0	0	-9999	-10000	0	0
CTDSPL	-0.001	0.033	-9999	-0.74	1	1
PPP1CA	0	0	-9999	-10000	0	0
XIAP	0	0	-9999	-10000	0	0
CTDSP1	0	0	-9999	-10000	0	0
PPP1R15A	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.084	0.14	-9999	-0.46	43	43
CHRD	-0.004	0.053	-9999	-0.68	3	3
BMPR2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.071	0.14	-9999	-0.49	29	29
BMP4	-0.017	0.11	-9999	-0.72	12	12
FST	-0.097	0.22	-9999	-0.58	84	84
BMP2-4/NOG	-0.09	0.21	-9999	-0.53	83	83
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.13	0.17	-9999	-0.49	44	44

×

Canonical Wnt signaling pathway

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
HDAC1	0.004	0.018	-10000	0	-10000	0	0
AES	0.003	0.015	-10000	0	-10000	0	0
FBXW11	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0	0	-10000	0	-10000	0	0
SMAD4	0	0	-10000	0	-10000	0	0
DKK2	-0.14	0.29	-10000	0	-0.74	93	93
TLE1	0.002	0.031	-10000	0	-0.61	1	1
MACF1	0.004	0.047	-10000	0	-0.74	2	2
CTNNB1	0.066	0.099	0.28	12	-10000	0	12
WIF1	-0.47	0.36	-10000	0	-0.74	318	318
beta catenin/RanBP3	0.002	0.091	0.39	22	-10000	0	22
KREMEN2	-0.37	0.28	-10000	0	-0.57	325	325
DKK1	-0.039	0.15	-10000	0	-0.62	31	31
beta catenin/beta TrCP1	0.068	0.093	0.28	10	-10000	0	10
FZD1	0.004	0.005	-10000	0	-10000	0	0
AXIN2	-0.036	0.28	-10000	0	-1.5	17	17
AXIN1	0.008	0.005	-10000	0	-10000	0	0
RAN	0.001	0.003	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.005	0.021	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.092	0.054	-10000	0	-10000	0	0
Axin1/APC/GSK3	0.02	0.063	0.24	30	-10000	0	30
Axin1/APC/GSK3/beta catenin/Macf1	0.065	0.042	-10000	0	-10000	0	0
HNF1A	-0.006	0.075	-10000	0	-0.58	8	8
CTBP1	0.004	0.017	-10000	0	-10000	0	0
MYC	0.008	0.048	-10000	0	-10000	0	0
RANBP3	0.001	0.003	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.31	0.25	-10000	0	-0.44	349	349
NKD1	-0.071	0.22	-10000	0	-0.72	49	49
TCF4	-0.001	0.058	-10000	0	-0.72	3	3
TCF3	0.004	0.017	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	-0.002	0.023	-10000	0	-10000	0	0
Ran/GTP	0	0.002	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.017	0.094	0.45	21	-10000	0	21
LEF1	0.002	0.031	-10000	0	-0.58	1	1
DVL1	0.08	0.061	0.21	1	-10000	0	1
CSNK2A1	0.003	0.005	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.097	0.071	-10000	0	-0.56	1	1
DKK1/LRP6/Kremen 2	-0.25	0.19	-10000	0	-0.37	334	334
LRP6	0.007	0.005	-10000	0	-10000	0	0
CSNK1A1	0.004	0.018	-10000	0	-10000	0	0
NLK	0.01	0.002	-10000	0	-10000	0	0
CCND1	-0.008	0.17	-10000	0	-1.5	6	6
WNT1	0.003	0.045	-10000	0	-0.57	3	3
GSK3A	0.008	0.005	-10000	0	-10000	0	0
GSK3B	0.003	0.004	-10000	0	-10000	0	0
FRAT1	-0.001	0.033	-10000	0	-0.74	1	1
PPP2R5D	0.076	0.1	0.37	49	-10000	0	49
APC	0	0.023	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.16	0.12	0.26	315	-10000	0	315
CREBBP	0.004	0.017	-10000	0	-10000	0	0

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	-0.019	0.082	-9999	-0.42	16	16
RGS9BP	-0.013	0.098	-9999	-0.74	9	9
mol:GTP	0	0	-9999	-10000	0	0
GRK1	-0.002	0.036	-9999	-0.57	2	2
mol:Na +	-0.18	0.18	-9999	-0.36	253	253
mol:ADP	-0.012	0.099	-9999	-0.42	28	28
GNAT2	0	0	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.059	0.16	-9999	-0.49	60	60
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0	0	-9999	-10000	0	0
GRK7	-0.03	0.13	-9999	-0.57	26	26
CNGB3	-0.29	0.29	-9999	-0.57	251	251
Cone Metarhodopsin II/X-Arrestin	0	0	-9999	-10000	0	0
mol:Ca2+	-0.21	0.21	-9999	-0.63	46	46
Cone PDE6	-0.051	0.14	-9999	-0.68	3	3
Cone Metarhodopsin II	-0.018	0.075	-9999	-0.33	28	28
Na + (4 Units)	-0.22	0.2	-9999	-0.62	46	46
GNAT2/GDP	-0.05	0.14	-9999	-0.42	60	60
GNB5	0	0	-9999	-10000	0	0
mol:GMP (4 units)	0.009	0.005	-9999	-10000	0	0
Cone Transducin	-0.02	0.087	-9999	-0.44	16	16
SLC24A2	-0.11	0.23	-9999	-0.57	97	97
GNB3/GNGT2	-0.025	0.11	-9999	-0.5	25	25
GNB3	-0.01	0.076	-9999	-0.57	9	9
GNAT2/GTP	0	0	-9999	-10000	0	0
CNGA3	-0.002	0.036	-9999	-0.57	2	2
ARR3	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.18	0.18	-9999	-0.36	253	253
mol:Pi	-0.058	0.16	-9999	-0.49	60	60
Cone CNG Channel	-0.14	0.14	-9999	-10000	0	0
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.11	0.23	-9999	-0.57	97	97
RGS9	-0.078	0.23	-9999	-0.74	53	53
PDE6C	0	0	-9999	-10000	0	0
GNGT2	-0.024	0.13	-9999	-0.74	16	16
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0	0	-9999	-10000	0	0

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	-0.034	0.11	-10000	0	-0.39	43	43
fibroblast growth factor receptor signaling pathway	-0.033	0.11	-10000	0	-0.39	43	43
LAMA1	-0.17	0.26	-10000	0	-0.58	146	146
PRNP	0	0	-10000	0	-10000	0	0
GPC1/SLIT2	-0.14	0.25	-10000	0	-0.56	130	130
SMAD2	-0.023	0.14	-10000	0	-0.43	37	37
GPC1/PrPc/Cu2+	-0.02	0.081	-10000	0	-0.35	28	28
GPC1/Laminin alpha1	-0.14	0.22	-10000	0	-0.45	158	158
TDGF1	-0.003	0.044	-10000	0	-0.57	3	3
CRIPTO/GPC1	-0.026	0.1	-10000	0	-0.42	31	31
APP/GPC1	-0.023	0.095	-10000	0	-0.42	28	28
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.001	0.089	-10000	0	-0.35	31	31
FLT1	0	0	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	-0.055	0.14	-10000	0	-0.48	37	37
SERPINC1	-0.007	0.063	-10000	0	-0.57	6	6
FYN	-0.002	0.092	-10000	0	-0.35	32	32
FGR	-0.037	0.16	-10000	0	-0.43	66	66
positive regulation of MAPKKK cascade	-0.001	0.12	-10000	0	-0.47	16	16
SLIT2	-0.16	0.3	-10000	0	-0.74	110	110
GPC1/NRG	-0.04	0.13	-10000	0	-0.46	43	43
NRG1	-0.022	0.13	-10000	0	-0.74	15	15
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.019	0.08	-10000	0	-0.35	28	28
LYN	-0.003	0.094	-10000	0	-0.36	33	33
mol:Spermine	-0.014	0.1	-10000	0	-0.42	28	28
cell growth	-0.033	0.11	-10000	0	-0.39	43	43
BMP signaling pathway	0.032	0.13	0.57	28	-10000	0	28
SRC	-0.001	0.089	-10000	0	-0.35	31	31
TGFBR1	0	0	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.22	0.34	-10000	0	-0.74	152	152
GPC1	-0.032	0.13	-10000	0	-0.57	28	28
TGFBR1 (dimer)	0	0	-10000	0	-10000	0	0
VEGFA	0	0	-10000	0	-10000	0	0
BLK	-0.024	0.13	-10000	0	-0.39	57	57
HCK	-0.007	0.1	-10000	0	-0.37	37	37
FGF2	-0.021	0.12	-10000	0	-0.74	14	14
FGFR1	-0.001	0.033	-10000	0	-0.74	1	1
VEGFR1 homodimer	0	0	-10000	0	-10000	0	0
TGFBR2	-0.054	0.19	-10000	0	-0.74	37	37
cell death	-0.023	0.095	-10000	0	-0.41	28	28
ATIII/GPC1	-0.028	0.1	-10000	0	-0.42	34	34
PLA2G2A/GPC1	-0.19	0.27	-10000	0	-0.56	169	169
LCK	-0.002	0.092	-10000	0	-0.35	32	32
neuron differentiation	-0.04	0.13	-10000	0	-0.46	43	43
PrPc/Cu2+	0	0	-10000	0	-10000	0	0
APP	0	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	-0.054	0.19	-10000	0	-0.74	37	37

×

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

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
MAP4K1	-0.009	0.14	-10000	0	-0.38	63	63
CRKL	-0.014	0.15	-10000	0	-0.41	63	63
HRAS	-0.06	0.14	-10000	0	-0.62	14	14
mol:PIP3	-0.025	0.14	-10000	0	-0.39	61	61
SPRED1	0	0	-10000	0	-10000	0	0
SPRED2	0	0	-10000	0	-10000	0	0
GAB1	-0.022	0.16	-10000	0	-0.43	63	63
FOXO3	-0.007	0.14	-10000	0	-0.37	61	61
AKT1	-0.016	0.14	-10000	0	-0.4	63	63
BAD	-0.007	0.14	-10000	0	-0.37	61	61
megakaryocyte differentiation	-0.051	0.21	-10000	0	-0.49	84	84
GSK3B	-0.007	0.14	-10000	0	-0.37	61	61
RAF1	0.004	0.14	-10000	0	-0.48	14	14
SHC1	0	0	-10000	0	-10000	0	0
STAT3	-0.022	0.16	-10000	0	-0.43	63	63
STAT1	-0.075	0.36	-10000	0	-1	63	63
HRAS/SPRED1	-0.048	0.11	-10000	0	-0.48	14	14
cell proliferation	-0.021	0.15	-10000	0	-0.42	63	63
PIK3CA	0	0	-10000	0	-10000	0	0
TEC	-0.003	0.046	-10000	0	-0.74	2	2
RPS6KB1	-0.022	0.16	-10000	0	-0.43	63	63
HRAS/SPRED2	-0.048	0.11	-10000	0	-0.48	14	14
LYN/TEC/p62DOK	-0.053	0.14	-10000	0	-0.41	63	63
MAPK3	0.018	0.1	-10000	0	-0.32	14	14
STAP1	-0.044	0.2	-10000	0	-0.5	76	76
GRAP2	-0.044	0.18	-10000	0	-0.74	30	30
JAK2	-0.11	0.28	-10000	0	-0.85	63	63
STAT1 (dimer)	-0.072	0.35	-10000	0	-0.99	63	63
mol:Gleevec	0	0.006	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.054	0.14	-10000	0	-0.4	63	63
actin filament polymerization	-0.021	0.15	-10000	0	-0.42	63	63
LYN	-0.003	0.046	-10000	0	-0.74	2	2
STAP1/STAT5A (dimer)	-0.049	0.25	-10000	0	-0.67	63	63
PIK3R1	0	0	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.045	0.12	-10000	0	-10000	0	0
PI3K	-0.05	0.13	-10000	0	-0.4	63	63
PTEN	-0.003	0.046	-10000	0	-0.74	2	2
SCF/KIT/EPO/EPOR	-0.1	0.44	-10000	0	-1.3	63	63
MAPK8	-0.022	0.16	-10000	0	-0.43	63	63
STAT3 (dimer)	-0.021	0.15	-10000	0	-0.42	63	63
positive regulation of transcription	0.019	0.085	-10000	0	-0.3	1	1
mol:GDP	-0.064	0.15	-10000	0	-0.66	14	14
PIK3C2B	-0.022	0.16	-10000	0	-0.43	63	63
CBL/CRKL	-0.007	0.14	-10000	0	-0.38	63	63
FER	-0.022	0.16	-10000	0	-0.43	63	63
SH2B3	-0.024	0.16	-10000	0	-0.43	65	65
PDPK1	-0.016	0.13	-10000	0	-0.36	61	61
SNAI2	-0.022	0.16	-10000	0	-0.43	63	63
positive regulation of cell proliferation	-0.045	0.26	-10000	0	-0.74	63	63
KITLG	0.013	0.005	-10000	0	-10000	0	0
cell motility	-0.045	0.26	-10000	0	-0.74	63	63
PTPN6	0.004	0.011	-10000	0	-10000	0	0
EPOR	0.01	0.1	-10000	0	-10000	0	0
STAT5A (dimer)	-0.032	0.22	-10000	0	-0.61	63	63
SOCS1	-0.001	0.033	-10000	0	-0.74	1	1
cell migration	0.036	0.18	0.44	76	-10000	0	76
SOS1	0	0	-10000	0	-10000	0	0
EPO	0.002	0.063	-10000	0	-0.57	6	6
VAV1	-0.007	0.073	-10000	0	-0.74	5	5
GRB10	-0.022	0.16	-10000	0	-0.43	63	63
PTPN11	0.003	0.009	-10000	0	-10000	0	0
SCF/KIT	-0.058	0.15	-10000	0	-0.46	63	63
GO:0007205	0	0.008	-10000	0	-10000	0	0
MAP2K1	0.015	0.11	-10000	0	-0.36	14	14
CBL	0	0	-10000	0	-10000	0	0
KIT	-0.13	0.47	-10000	0	-1.4	63	63
MAP2K2	0.015	0.11	-10000	0	-0.36	14	14
SHC/Grb2/SOS1	-0.05	0.13	-10000	0	-0.4	63	63
STAT5A	-0.035	0.22	-10000	0	-0.63	63	63
GRB2	0	0	-10000	0	-10000	0	0
response to radiation	-0.021	0.15	-10000	0	-0.42	63	63
SHC/GRAP2	-0.033	0.13	-10000	0	-0.56	30	30
PTPRO	-0.053	0.21	-10000	0	-0.5	84	84
SH2B2	-0.022	0.16	-10000	0	-0.43	63	63
DOK1	0	0	-10000	0	-10000	0	0
MATK	-0.037	0.18	-10000	0	-0.46	76	76
CREBBP	0.028	0.011	-10000	0	-10000	0	0
BCL2	0.01	0.1	-10000	0	-10000	0	0

×

Presenilin action in Notch and Wnt 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
Delta 1/NOTCH/NOTCH(cleaved)	0	0	-10000	0	-10000	0	0
HDAC1	0.001	0.005	-10000	0	-10000	0	0
AES	0	0.002	-10000	0	-10000	0	0
FBXW11	0	0	-10000	0	-10000	0	0
DTX1	-0.002	0.036	-10000	0	-0.57	2	2
LRP6/FZD1	0	0	-10000	0	-10000	0	0
TLE1	-0.001	0.032	-10000	0	-0.73	1	1
AP1	-0.08	0.19	-10000	0	-0.43	92	92
NCSTN	0	0	-10000	0	-10000	0	0
ADAM10	0	0.001	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.002	0.042	-10000	0	-0.55	1	1
NICD/RBPSUH	0	0	-10000	0	-10000	0	0
WIF1	-0.47	0.36	-10000	0	-0.74	318	318
NOTCH1	0	0	-10000	0	-10000	0	0
PSENEN	0	0	-10000	0	-10000	0	0
KREMEN2	-0.37	0.28	-10000	0	-0.57	325	325
DKK1	-0.039	0.15	-10000	0	-0.62	31	31
beta catenin/beta TrCP1	0.016	0.06	-10000	0	-10000	0	0
APH1B	0	0	-10000	0	-10000	0	0
APH1A	0	0	-10000	0	-10000	0	0
AXIN1	-0.004	0.026	0.3	1	-10000	0	1
CtBP/CBP/TCF1/TLE1/AES	-0.001	0.027	-10000	0	-10000	0	0
PSEN1	0	0	-10000	0	-10000	0	0
FOS	-0.09	0.24	-10000	0	-0.74	61	61
JUN	0	0	-10000	0	-10000	0	0
MAP3K7	0	0.003	-10000	0	-10000	0	0
CTNNB1	0.01	0.065	0.22	16	-10000	0	16
MAPK3	0	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.31	0.25	-10000	0	-0.44	349	349
HNF1A	-0.009	0.072	-10000	0	-0.58	8	8
CTBP1	0	0.002	-10000	0	-10000	0	0
MYC	0.002	0.012	-10000	0	-10000	0	0
NKD1	-0.071	0.22	-10000	0	-0.72	49	49
FZD1	0	0	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.001	0.018	-10000	0	-10000	0	0
apoptosis	-0.079	0.19	-10000	0	-0.42	92	92
Delta 1/NOTCHprecursor	0	0	-10000	0	-10000	0	0
DLL1	0	0	-10000	0	-10000	0	0
PPARD	0.002	0.012	-10000	0	-10000	0	0
Gamma Secretase	0	0	-10000	0	-10000	0	0
APC	-0.004	0.026	0.3	1	-10000	0	1
DVL1	-0.045	0.043	-10000	0	-0.67	1	1
CSNK2A1	0.01	0.001	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.25	0.19	-10000	0	-0.37	334	334
LRP6	0	0	-10000	0	-10000	0	0
CSNK1A1	0.01	0.001	-10000	0	-10000	0	0
NLK	0.001	0.006	-10000	0	-10000	0	0
CCND1	-0.015	0.16	-10000	0	-1.4	6	6
WNT1	-0.003	0.044	-10000	0	-0.58	3	3
Axin1/APC/beta catenin	0.011	0.045	0.27	1	-0.36	1	2
DKK2	-0.14	0.29	-10000	0	-0.74	93	93
NOTCH1 precursor/DVL1	-0.022	0.028	-10000	0	-0.55	1	1
GSK3B	0	0.002	-10000	0	-10000	0	0
FRAT1	-0.001	0.033	-10000	0	-0.74	1	1
NOTCH/Deltex homolog 1	-0.001	0.018	-10000	0	-10000	0	0
PPP2R5D	0.01	0.1	0.31	49	-10000	0	49
MAPK1	0	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.28	0.21	-10000	0	-0.43	317	317
RBPJ	0	0	-10000	0	-10000	0	0
CREBBP	0.013	0.002	-10000	0	-10000	0	0

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.031	0.13	-9999	-0.56	28	28
alphaV beta3 Integrin	-0.024	0.11	-9999	-0.49	24	24
PTK2	-0.19	0.23	-9999	-0.7	43	43
IGF1R	0	0	-9999	-10000	0	0
PI4KB	0	0	-9999	-10000	0	0
MFGE8	0	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
CDKN1B	-0.22	0.29	-9999	-0.58	189	189
VEGFA	0	0	-9999	-10000	0	0
ILK	-0.22	0.29	-9999	-0.58	189	189
ROCK1	0	0	-9999	-10000	0	0
AKT1	-0.21	0.27	-9999	-0.54	189	189
PTK2B	0.002	0.13	-9999	-0.48	32	32
alphaV/beta3 Integrin/JAM-A	-0.17	0.22	-9999	-0.43	194	194
CBL	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.013	0.076	-9999	-0.44	15	15
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.016	0.081	-9999	-0.43	18	18
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.12	0.16	-9999	-0.66	20	20
alphaV/beta3 Integrin/Syndecan-1	-0.011	0.073	-9999	-0.48	12	12
PI4KA	0	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.041	0.14	-9999	-0.78	11	11
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.19	0.18	-9999	-0.59	11	11
RPS6KB1	-0.038	0.13	-9999	-0.72	11	11
TLN1	0	0	-9999	-10000	0	0
MAPK3	-0.1	0.18	-9999	-0.75	24	24
GPR124	-0.001	0.033	-9999	-0.74	1	1
MAPK1	-0.1	0.18	-9999	-0.75	24	24
PXN	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.31	0.25	-9999	-0.49	313	313
cell adhesion	-0.014	0.073	-9999	-0.44	11	11
ANGPTL3	-0.005	0.051	-9999	-0.57	4	4
VEGFR2 homodimer/VEGFA homodimer/Src	-0.027	0.11	-9999	-0.48	28	28
IGF-1R heterotetramer	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	-0.054	0.19	-9999	-0.74	37	37
ITGB3	-0.016	0.11	-9999	-0.74	11	11
IGF1	-0.028	0.14	-9999	-0.73	19	19
RAC1	0	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.011	0.072	-9999	-0.47	12	12
apoptosis	0	0	-9999	-10000	0	0
CD47	-0.004	0.057	-9999	-0.74	3	3
alphaV/beta3 Integrin/CD47	-0.013	0.078	-9999	-0.48	14	14
VCL	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.04	0.14	-9999	-0.5	40	40
CSF1	-0.006	0.066	-9999	-0.74	4	4
PIK3C2A	-0.22	0.29	-9999	-0.58	189	189
PI4 Kinase/Pyk2	-0.16	0.21	-9999	-0.76	25	25
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.033	0.14	-9999	-0.52	32	32
FAK1/Vinculin	-0.14	0.18	-9999	-0.52	43	43
alphaV beta3/Integrin/ppsTEM5	-0.011	0.073	-9999	-0.48	12	12
RHOA	0	0	-9999	-10000	0	0
VTN	-0.28	0.36	-9999	-0.74	191	191
BCAR1	0	0	-9999	-10000	0	0
FGF2	-0.021	0.12	-9999	-0.74	14	14
F11R	0.004	0.095	-9999	-0.56	14	14
alphaV/beta3 Integrin/Lactadherin	-0.01	0.07	-9999	-0.48	11	11
alphaV/beta3 Integrin/TGFBR2	-0.045	0.16	-9999	-0.55	41	41
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.003	0.038	-9999	-0.43	4	4
HSP90AA1	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.01	0.064	-9999	-0.44	11	11
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.019	0.12	-9999	-0.74	13	13
alphaV/beta3 Integrin/Pyk2	-0.031	0.13	-9999	-0.49	32	32
SDC1	-0.001	0.033	-9999	-0.74	1	1
VAV3	0.031	0.043	-9999	-0.4	5	5
PTPN11	0	0	-9999	-10000	0	0
IRS1	0	0	-9999	-10000	0	0
FAK1/Paxillin	-0.14	0.18	-9999	-0.52	43	43
cell migration	-0.13	0.16	-9999	-0.48	35	35
ITGAV	0	0	-9999	-10000	0	0
PI3K	-0.15	0.2	-9999	-0.76	13	13
SPP1	-0.29	0.29	-9999	-0.57	255	255
KDR	-0.041	0.17	-9999	-0.74	28	28
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0	0	-9999	-10000	0	0
COL4A3	-0.46	0.36	-9999	-0.74	313	313
angiogenesis	-0.11	0.22	-9999	-0.74	26	26
Rac1/GTP	-0.004	0.036	-9999	-10000	0	0
EDIL3	-0.046	0.18	-9999	-0.74	31	31
cell proliferation	-0.045	0.16	-9999	-0.55	41	41

×

Nongenotropic Androgen signaling

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
PTK2	0.01	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.095	0.18	-10000	0	-0.44	109	109
regulation of S phase of mitotic cell cycle	-0.062	0.13	-10000	0	-0.31	103	103
GNAO1	-0.004	0.049	-10000	0	-0.63	3	3
HRAS	0	0	-10000	0	-10000	0	0
SHBG/T-DHT	0	0	-10000	0	-10000	0	0
PELP1	0	0	-10000	0	-10000	0	0
AKT1	0.01	0	-10000	0	-10000	0	0
MAP2K1	-0.049	0.16	-10000	0	-0.46	18	18
T-DHT/AR	-0.12	0.23	-10000	0	-0.56	103	103
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.002	-10000	0	-0.007	61	61
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.001	0.033	-10000	0	-0.74	1	1
mol:GDP	-0.11	0.22	-10000	0	-0.55	103	103
cell proliferation	-0.058	0.2	-10000	0	-0.65	18	18
PIK3CA	0	0	-10000	0	-10000	0	0
FOS	-0.09	0.3	-10000	0	-0.86	61	61
mol:Ca2+	-0.012	0.022	-10000	0	-0.069	26	26
MAPK3	-0.052	0.18	-10000	0	-0.58	18	18
MAPK1	-0.022	0.096	-10000	0	-0.3	18	18
PIK3R1	0	0	-10000	0	-10000	0	0
mol:IP3	0	0.002	-10000	0	-0.004	61	61
cAMP biosynthetic process	0.011	0.021	-10000	0	-10000	0	0
GNG2	-0.007	0.073	-10000	0	-0.74	5	5
potassium channel inhibitor activity	0	0.002	-10000	0	-0.004	61	61
HRAS/GTP	-0.084	0.16	-10000	0	-0.4	103	103
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0	0	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.002	-10000	0	-0.004	61	61
PI3K	0	0	-10000	0	-10000	0	0
apoptosis	0.048	0.18	0.45	61	-10000	0	61
T-DHT/AR/PELP1	-0.1	0.2	-10000	0	-0.49	103	103
HRAS/GDP	-0.11	0.21	-10000	0	-0.52	103	103
CREB1	-0.053	0.19	-10000	0	-0.48	61	61
RAC1-CDC42/GTP	0	0	-10000	0	-10000	0	0
AR	-0.15	0.3	-10000	0	-0.74	103	103
GNB1	-0.001	0.033	-10000	0	-0.74	1	1
RAF1	-0.056	0.17	-10000	0	-0.38	103	103
RAC1-CDC42/GDP	-0.1	0.2	-10000	0	-0.5	103	103
T-DHT/AR/PELP1/Src	-0.091	0.18	-10000	0	-0.44	103	103
MAP2K2	-0.049	0.16	-10000	0	-0.46	18	18
T-DHT/AR/PELP1/Src/PI3K	-0.063	0.13	-10000	0	-0.31	103	103
GNAZ	-0.009	0.08	-10000	0	-0.74	6	6
SHBG	0	0	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.023	0.064	-10000	0	-0.62	3	3
mol:T-DHT	0	0.001	-10000	0	-0.003	43	43
RAC1	0	0	-10000	0	-10000	0	0
GNRH1	0.007	0.036	-10000	0	-0.56	2	2
Gi family/GTP	-0.042	0.084	-10000	0	-0.36	8	8
CDC42	0	0	-10000	0	-10000	0	0

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.001	0.033	-9999	-0.74	1	1
alphaV beta3 Integrin	-0.012	0.081	-9999	-0.56	11	11
PTK2	-0.11	0.17	-9999	-0.58	44	44
positive regulation of JNK cascade	-0.035	0.092	-9999	-0.34	40	40
CDC42/GDP	-0.023	0.14	-9999	-0.47	40	40
Rac1/GDP	-0.021	0.14	-9999	-0.46	40	40
RAP1B	0	0	-9999	-10000	0	0
RAP1A	0	0	-9999	-10000	0	0
CTNNB1	0	0	-9999	-10000	0	0
CDC42/GTP	-0.043	0.11	-9999	-0.42	40	40
nectin-3/I-afadin	-0.044	0.15	-9999	-0.56	40	40
RAPGEF1	-0.034	0.15	-9999	-0.54	40	40
mol:GTP	0	0	-9999	-10000	0	0
CRK	-0.048	0.18	-9999	-0.62	40	40
PDGFB-D/PDGFRB	-0.001	0.033	-9999	-0.74	1	1
TLN1	-0.021	0.15	-9999	-0.52	33	33
Rap1/GTP	-0.036	0.099	-9999	-0.4	22	22
IQGAP1	0	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.044	0.15	-9999	-0.56	40	40
PVR	0	0	-9999	-10000	0	0
Necl-5(dimer)	0	0	-9999	-10000	0	0
mol:GDP	-0.035	0.17	-9999	-0.58	40	40
MLLT4	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
PI3K	-0.033	0.11	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.2	0.21	-9999	-0.42	238	238
positive regulation of lamellipodium assembly	-0.038	0.098	-9999	-0.36	43	43
PVRL1	-0.27	0.29	-9999	-0.57	238	238
PVRL3	-0.059	0.2	-9999	-0.74	40	40
PVRL2	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
CDH1	0	0	-9999	-10000	0	0
CLDN1	-0.1	0.22	-9999	-0.58	88	88
JAM-A/CLDN1	-0.089	0.17	-9999	-0.48	41	41
SRC	-0.079	0.19	-9999	-0.71	40	40
ITGB3	-0.016	0.11	-9999	-0.74	11	11
nectin-1(dimer)/I-afadin/I-afadin	-0.2	0.21	-9999	-0.42	238	238
FARP2	-0.039	0.16	-9999	-0.57	40	40
RAC1	0	0	-9999	-10000	0	0
CTNNA1	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.038	0.13	-9999	-0.48	40	40
nectin-1/I-afadin	-0.2	0.21	-9999	-0.42	238	238
nectin-2/I-afadin	0	0	-9999	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.2	0.21	-9999	-0.63	40	40
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.035	0.092	-9999	-0.34	40	40
alphaV/beta3 Integrin/Talin	-0.051	0.15	-9999	-0.78	14	14
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
PIP5K1C	-0.052	0.16	-9999	-0.56	33	33
VAV2	-0.043	0.17	-9999	-0.58	43	43
RAP1/GDP	-0.04	0.12	-9999	-0.43	40	40
ITGAV	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.038	0.13	-9999	-0.48	40	40
nectin-3(dimer)/I-afadin/I-afadin	-0.044	0.15	-9999	-0.56	40	40
Rac1/GTP	-0.046	0.12	-9999	-0.44	43	43
PTPRM	-0.057	0.17	-9999	-0.45	64	64
E-cadherin/beta catenin/alpha catenin	-0.12	0.13	-9999	-10000	0	0
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.19	0.22	-10000	0	-0.43	233	233
TP53	-0.052	0.058	-10000	0	-0.38	1	1
Senescence	-0.051	0.058	-10000	0	-0.38	1	1
Apoptosis	-0.051	0.058	-10000	0	-0.38	1	1
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.097	0.11	0.31	5	-0.43	1	6
MDM4	0	0	-10000	0	-10000	0	0

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.011	0.037	-9999	-0.53	1	1
NFATC2	-0.06	0.18	-9999	-0.51	70	70
NFATC3	0.012	0.028	-9999	-10000	0	0
CD40LG	-0.17	0.38	-9999	-0.78	115	115
PTGS2	-0.14	0.34	-9999	-0.69	114	114
JUNB	-0.001	0.033	-9999	-0.74	1	1
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.005	0.011	-9999	-10000	0	0
CaM/Ca2+	-0.005	0.011	-9999	-10000	0	0
CALM1	-0.001	0.003	-9999	-10000	0	0
JUN	-0.001	0.003	-9999	-10000	0	0
mol:Ca2+	-0.006	0.01	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0.002	-9999	-10000	0	0
FOSL1	-0.003	0.044	-9999	-0.57	3	3
CREM	0	0	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.1	0.17	-9999	-0.55	47	47
FOS	-0.091	0.24	-9999	-0.74	61	61
IFNG	-0.11	0.29	-9999	-0.64	75	75
AP-1/NFAT1-c-4	-0.21	0.3	-9999	-0.75	94	94
FASLG	-0.12	0.31	-9999	-0.68	81	81
NFAT1-c-4/ICER1	-0.082	0.16	-9999	-0.5	47	47
IL2RA	-0.11	0.29	-9999	-0.64	77	77
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	-0.14	0.34	-9999	-0.69	106	106
JunB/Fra1/NFAT1-c-4	-0.08	0.15	-9999	-0.49	46	46
IL4	-0.11	0.29	-9999	-0.64	69	69
IL2	-0.004	0.014	-9999	-10000	0	0
IL3	-0.019	0.023	-9999	-10000	0	0
FKBP1A	0	0	-9999	-10000	0	0
BATF3	0	0	-9999	-10000	0	0
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0	0.003	-9999	-10000	0	0

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.26	0.34	-10000	0	-0.83	53	53
PCK1	-0.13	0.21	-10000	0	-0.73	18	18
HNF4A	-0.31	0.4	-10000	0	-1	51	51
KCNJ11	-0.27	0.38	-10000	0	-1	32	32
AKT1	0	0.088	-10000	0	-10000	0	0
response to starvation	-0.01	0.034	-10000	0	-10000	0	0
DLK1	-0.29	0.37	-10000	0	-0.95	46	46
NKX2-1	-0.77	0.79	0.48	1	-1.5	260	261
ACADM	-0.26	0.34	-10000	0	-0.83	52	52
TAT	-0.12	0.19	-10000	0	-0.75	9	9
CEBPB	0.003	0.006	-10000	0	-10000	0	0
CEBPA	0.002	0.034	-10000	0	-0.74	1	1
TTR	-0.052	0.19	-10000	0	-0.75	20	20
PKLR	-0.27	0.34	-10000	0	-0.85	53	53
APOA1	-0.43	0.56	-10000	0	-1.3	92	92
CPT1C	-0.26	0.34	-10000	0	-0.83	53	53
ALAS1	-0.11	0.18	-10000	0	-10000	0	0
TFRC	-0.16	0.25	-10000	0	-0.87	11	11
FOXF1	0	0.24	0.26	10	-0.62	58	68
NF1	0.016	0	-10000	0	-10000	0	0
HNF1A (dimer)	-0.012	0.081	-10000	0	-0.6	8	8
CPT1A	-0.26	0.34	-10000	0	-0.83	53	53
HMGCS1	-0.26	0.34	-10000	0	-0.83	53	53
NR3C1	0.017	0.012	-10000	0	-10000	0	0
CPT1B	-0.26	0.34	-10000	0	-0.86	40	40
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	-0.005	0.029	-10000	0	-10000	0	0
GCK	-0.26	0.34	-10000	0	-0.84	53	53
CREB1	0.007	0.017	-10000	0	-10000	0	0
IGFBP1	-0.12	0.17	-10000	0	-0.67	3	3
PDX1	-0.17	0.24	-10000	0	-0.74	5	5
UCP2	-0.26	0.34	-10000	0	-0.83	53	53
ALDOB	-0.26	0.36	-10000	0	-0.91	33	33
AFP	0.017	0.14	-10000	0	-0.68	5	5
BDH1	-0.26	0.34	-10000	0	-0.91	27	27
HADH	-0.26	0.36	-10000	0	-0.89	32	32
F2	-0.34	0.42	-10000	0	-1.1	50	50
HNF1A	-0.012	0.082	-10000	0	-0.6	8	8
G6PC	0.01	0.088	-10000	0	-0.63	2	2
SLC2A2	-0.17	0.23	-10000	0	-0.87	2	2
INS	-0.009	0.011	-10000	0	-10000	0	0
FOXA1	0.072	0.14	0.3	35	-0.57	11	46
FOXA3	-0.009	0.15	-10000	0	-0.7	18	18
FOXA2	-0.31	0.41	-10000	0	-0.91	66	66
ABCC8	-0.28	0.38	-10000	0	-1	35	35
ALB	0.025	0.13	-10000	0	-0.63	6	6

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.2	0.44	-9999	-1.2	35	35
HDAC7	-0.006	0.013	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.2	0.34	-9999	-0.91	36	36
SMAD4	0	0.002	-9999	-10000	0	0
ID2	-0.2	0.44	-9999	-1.2	36	36
AP1	-0.07	0.18	-9999	-0.56	61	61
ABCG2	-0.25	0.5	-9999	-1.3	59	59
HIF1A	-0.024	0.071	-9999	-10000	0	0
TFF3	-0.24	0.48	-9999	-1.3	46	46
GATA2	-0.073	0.23	-9999	-0.74	55	55
AKT1	-0.033	0.059	-9999	-10000	0	0
response to hypoxia	-0.047	0.065	-9999	-10000	0	0
MCL1	-0.2	0.44	-9999	-1.2	35	35
NDRG1	-0.21	0.44	-9999	-1.3	34	34
SERPINE1	-0.2	0.44	-9999	-1.3	33	33
FECH	-0.2	0.44	-9999	-1.2	36	36
FURIN	-0.2	0.44	-9999	-1.2	36	36
NCOA2	0.008	0.034	-9999	-0.74	1	1
EP300	-0.024	0.09	-9999	-10000	0	0
HMOX1	-0.21	0.44	-9999	-1.2	37	37
BHLHE40	-0.2	0.44	-9999	-1.2	35	35
BHLHE41	-0.21	0.45	-9999	-1.3	36	36
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.033	0.084	-9999	-0.5	6	6
ENG	0.001	0.14	-9999	-0.83	9	9
JUN	0.008	0.005	-9999	-10000	0	0
RORA	-0.2	0.44	-9999	-1.2	36	36
ABCB1	-0.2	0.44	-9999	-1.4	59	59
TFRC	-0.2	0.44	-9999	-1.2	36	36
CXCR4	-0.2	0.44	-9999	-1.2	34	34
TF	-0.23	0.46	-9999	-1.3	40	40
CITED2	-0.21	0.45	-9999	-1.3	35	35
HIF1A/ARNT	-0.25	0.5	-9999	-1.4	44	44
LDHA	-0.034	0.047	-9999	-10000	0	0
ETS1	-0.21	0.45	-9999	-1.3	36	36
PGK1	-0.2	0.44	-9999	-1.2	35	35
NOS2	-0.25	0.48	-9999	-1.3	47	47
ITGB2	-0.22	0.46	-9999	-1.3	39	39
ALDOA	-0.2	0.44	-9999	-1.2	36	36
Cbp/p300/CITED2	-0.25	0.44	-9999	-1.3	41	41
FOS	-0.082	0.25	-9999	-0.74	61	61
HK2	-0.2	0.44	-9999	-1.2	36	36
SP1	0.011	0.025	-9999	-10000	0	0
GCK	-0.03	0.14	-9999	-0.74	1	1
HK1	-0.2	0.44	-9999	-1.2	36	36
NPM1	-0.2	0.44	-9999	-1.2	35	35
EGLN1	-0.2	0.44	-9999	-1.2	35	35
CREB1	0.017	0	-9999	-10000	0	0
PGM1	-0.2	0.44	-9999	-1.2	36	36
SMAD3	0	0.002	-9999	-10000	0	0
EDN1	-0.17	0.4	-9999	-1.2	53	53
IGFBP1	-0.21	0.44	-9999	-1.2	35	35
VEGFA	-0.24	0.32	-9999	-0.86	28	28
HIF1A/JAB1	-0.018	0.029	-9999	-10000	0	0
CP	-0.23	0.47	-9999	-1.3	39	39
CXCL12	-0.23	0.49	-9999	-1.3	48	48
COPS5	0.009	0.005	-9999	-10000	0	0
SMAD3/SMAD4	-0.001	0.004	-9999	-10000	0	0
BNIP3	-0.2	0.44	-9999	-1.2	39	39
EGLN3	-0.25	0.47	-9999	-1.3	45	45
CA9	-0.43	0.47	-9999	-1.3	65	65
TERT	-0.31	0.49	-9999	-1.3	51	51
ENO1	-0.2	0.44	-9999	-1.2	33	33
PFKL	-0.2	0.44	-9999	-1.2	33	33
NCOA1	0.003	0.005	-9999	-10000	0	0
ADM	-0.21	0.44	-9999	-1.3	32	32
ARNT	-0.024	0.07	-9999	-10000	0	0
HNF4A	0.002	0.074	-9999	-0.58	8	8
ADFP	-0.21	0.44	-9999	-1.2	42	42
SLC2A1	-0.44	0.36	-9999	-0.97	82	82
LEP	-0.26	0.48	-9999	-1.2	49	49
HIF1A/ARNT/Cbp/p300	-0.21	0.35	-9999	-0.92	44	44
EPO	-0.084	0.25	-9999	-0.83	3	3
CREBBP	-0.024	0.09	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/HDAC7	-0.26	0.38	-9999	-0.98	48	48
PFKFB3	-0.2	0.44	-9999	-1.2	36	36
NT5E	-0.21	0.44	-9999	-1.3	33	33

×

Coregulation of Androgen receptor activity

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
NRIP1	0.002	0.004	-9999	-10000	0	0
SVIL	0.002	0.004	-9999	-10000	0	0
ZNF318	0	0.005	-9999	-10000	0	0
JMJD2C	-0.004	0.026	-9999	-0.081	50	50
T-DHT/AR/Ubc9	-0.13	0.2	-9999	-0.52	103	103
CARM1	0	0	-9999	-10000	0	0
PRDX1	0	0.001	-9999	-10000	0	0
PELP1	0	0.001	-9999	-10000	0	0
CTNNB1	0.001	0.004	-9999	-10000	0	0
AKT1	0	0.002	-9999	-10000	0	0
PTK2B	0.001	0.004	-9999	-10000	0	0
MED1	0	0.002	-9999	-10000	0	0
MAK	-0.066	0.21	-9999	-0.74	45	45
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	0.002	0.004	-9999	-10000	0	0
GSN	0.002	0.004	-9999	-10000	0	0
NCOA2	-0.001	0.033	-9999	-0.74	1	1
NCOA6	0.002	0.004	-9999	-10000	0	0
DNA-PK	0	0.006	-9999	-10000	0	0
NCOA4	0	0	-9999	-10000	0	0
PIAS3	0.001	0.004	-9999	-10000	0	0
cell proliferation	-0.11	0.27	-9999	-0.94	45	45
XRCC5	0	0.002	-9999	-10000	0	0
UBE3A	0.002	0.004	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.14	0.22	-9999	-0.54	114	114
FHL2	-0.054	0.08	-9999	-0.56	2	2
RANBP9	0.002	0.004	-9999	-10000	0	0
JMJD1A	-0.034	0.07	-9999	-0.13	162	162
CDK6	-0.002	0.036	-9999	-0.57	2	2
TGFB1I1	0.002	0.004	-9999	-10000	0	0
T-DHT/AR/CyclinD1	-0.14	0.21	-9999	-0.53	108	108
XRCC6	0	0.002	-9999	-10000	0	0
T-DHT/AR	-0.14	0.24	-9999	-0.55	104	104
CTDSP1	0.001	0.004	-9999	-10000	0	0
CTDSP2	0	0.004	-9999	-10000	0	0
BRCA1	0.002	0.004	-9999	-10000	0	0
TCF4	-0.004	0.057	-9999	-0.74	3	3
CDKN2A	-0.27	0.29	-9999	-0.58	233	233
SRF	0.016	0.007	-9999	-10000	0	0
NKX3-1	-0.11	0.14	-9999	-0.95	2	2
KLK3	0.031	0.054	-9999	-10000	0	0
TMF1	0.001	0.003	-9999	-10000	0	0
HNRNPA1	0	0.002	-9999	-10000	0	0
AOF2	0	0.002	-9999	-10000	0	0
APPL1	0.02	0.003	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.13	0.21	-9999	-0.52	103	103
AR	-0.16	0.31	-9999	-0.76	103	103
UBA3	0.001	0.004	-9999	-10000	0	0
PATZ1	0	0.002	-9999	-10000	0	0
PAWR	0.001	0.003	-9999	-10000	0	0
PRKDC	0	0.002	-9999	-10000	0	0
PA2G4	0	0.003	-9999	-10000	0	0
UBE2I	0	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.12	0.19	-9999	-0.48	103	103
RPS6KA3	0.002	0.004	-9999	-10000	0	0
T-DHT/AR/ARA70	-0.13	0.2	-9999	-0.52	103	103
LATS2	0	0.002	-9999	-10000	0	0
T-DHT/AR/PRX1	-0.12	0.19	-9999	-0.48	103	103
Cyclin D3/CDK11 p58	0	0	-9999	-10000	0	0
VAV3	0	0.033	-9999	-0.74	1	1
KLK2	-0.093	0.14	-9999	-0.51	28	28
CASP8	0	0.001	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.12	0.19	-9999	-0.48	104	104
TMPRSS2	-0.4	0.54	-9999	-1.2	161	161
CCND1	-0.01	0.084	-9999	-0.71	7	7
PIAS1	0.002	0.004	-9999	-10000	0	0
mol:T-DHT	-0.019	0.036	-9999	-0.078	118	118
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.002	0.005	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.13	0.21	-9999	-0.52	105	105
CMTM2	-0.09	0.24	-9999	-0.74	61	61
SNURF	-0.024	0.13	-9999	-0.74	16	16
ZMIZ1	-0.007	0.047	-9999	-0.8	1	1
CCND3	0	0.001	-9999	-10000	0	0
TGIF1	0	0.002	-9999	-10000	0	0
FKBP4	0	0.026	-9999	-0.57	1	1

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.14	0.44	-10000	0	-1.3	39	39
IL23A	-0.14	0.43	-10000	0	-1.2	38	38
NF kappa B1 p50/RelA/I kappa B alpha	-0.21	0.36	-10000	0	-1.1	51	51
positive regulation of T cell mediated cytotoxicity	-0.15	0.46	-10000	0	-1.2	51	51
ITGA3	-0.13	0.41	-10000	0	-1.1	40	40
IL17F	-0.064	0.28	-10000	0	-0.74	29	29
IL12B	0.016	0.025	-10000	0	-10000	0	0
STAT1 (dimer)	-0.21	0.38	-10000	0	-1.1	51	51
CD4	-0.13	0.43	-10000	0	-1.3	37	37
IL23	-0.15	0.41	-10000	0	-1.2	38	38
IL23R	0.003	0.085	-10000	0	-10000	0	0
IL1B	-0.14	0.44	-10000	0	-1.3	36	36
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.13	0.4	-10000	0	-1.1	38	38
TYK2	0.011	0.019	-10000	0	-10000	0	0
STAT4	-0.012	0.092	-10000	0	-0.74	8	8
STAT3	0	0	-10000	0	-10000	0	0
IL18RAP	-0.023	0.15	-10000	0	-0.74	21	21
IL12RB1	-0.038	0.19	-10000	0	-0.77	32	32
PIK3CA	0	0	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	-0.026	0.15	-10000	0	-0.59	32	32
IL23R/JAK2	0.002	0.1	-10000	0	-10000	0	0
positive regulation of chronic inflammatory response	-0.15	0.46	-10000	0	-1.2	51	51
natural killer cell activation	0	0.007	-10000	0	-10000	0	0
JAK2	0.018	0.023	-10000	0	-10000	0	0
PIK3R1	0	0	-10000	0	-10000	0	0
NFKB1	0.006	0.006	-10000	0	-10000	0	0
RELA	0.006	0.006	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.14	0.39	-10000	0	-1.1	38	38
ALOX12B	-0.17	0.42	-10000	0	-1.1	47	47
CXCL1	-0.15	0.46	-10000	0	-1.3	46	46
T cell proliferation	-0.15	0.46	-10000	0	-1.2	51	51
NFKBIA	0.006	0.006	-10000	0	-10000	0	0
IL17A	-0.043	0.24	-10000	0	-0.6	20	20
PI3K	-0.21	0.36	-10000	0	-1.1	51	51
IFNG	0	0.028	0.099	1	-0.13	7	8
STAT3 (dimer)	-0.2	0.34	-10000	0	-1	48	48
IL18R1	0	0.074	-10000	0	-0.73	5	5
IL23/IL23R/JAK2/TYK2/SOCS3	-0.062	0.28	-10000	0	-0.83	23	23
IL18/IL18R	-0.026	0.12	-10000	0	-0.54	25	25
macrophage activation	-0.012	0.017	-10000	0	-0.045	27	27
TNF	-0.15	0.45	-10000	0	-1.3	41	41
STAT3/STAT4	-0.21	0.36	-10000	0	-1.1	51	51
STAT4 (dimer)	-0.22	0.39	-10000	0	-1.2	51	51
IL18	0.003	0.058	-10000	0	-0.74	3	3
IL19	-0.13	0.4	-10000	0	-1.1	34	34
STAT5A (dimer)	-0.21	0.38	-10000	0	-1.1	51	51
STAT1	0	0	-10000	0	-10000	0	0
SOCS3	-0.003	0.046	-10000	0	-0.74	2	2
CXCL9	-0.14	0.43	-10000	0	-1.3	38	38
MPO	-0.15	0.46	-10000	0	-1.2	53	53
positive regulation of humoral immune response	-0.15	0.46	-10000	0	-1.2	51	51
IL23/IL23R/JAK2/TYK2	-0.16	0.52	-10000	0	-1.3	51	51
IL6	-0.24	0.58	-10000	0	-1.3	96	96
STAT5A	0	0	-10000	0	-10000	0	0
IL2	0.006	0.008	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0	0.007	-10000	0	-10000	0	0
CD3E	-0.12	0.41	-10000	0	-1.2	32	32
keratinocyte proliferation	-0.15	0.46	-10000	0	-1.2	51	51
NOS2	-0.17	0.48	-10000	0	-1.3	49	49

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.016	0.13	-9999	-0.5	33	33
ADCY5	-0.028	0.15	-9999	-0.49	45	45
ADCY6	0.015	0.039	-9999	-0.48	3	3
ADCY7	0.017	0.022	-9999	-0.48	1	1
ADCY1	0.016	0.032	-9999	-0.48	2	2
ADCY2	-0.025	0.13	-9999	-0.41	50	50
ADCY3	0.017	0.022	-9999	-0.48	1	1
ADCY8	-0.14	0.23	-9999	-0.48	158	158
PRKCE	0.009	0.026	-9999	-0.56	1	1
ADCY9	0.016	0.032	-9999	-0.48	2	2
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.069	0.13	-9999	-0.44	27	27

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.01	0.059	-9999	-10000	0	0
Syndecan-3/Neurocan	-0.02	0.073	-9999	-10000	0	0
POMC	-0.055	0.17	-9999	-0.59	47	47
EGFR	-0.023	0.12	-9999	-0.63	18	18
Syndecan-3/EGFR	-0.012	0.061	-9999	-0.4	6	6
AGRP	-0.34	0.37	-9999	-0.74	233	233
NCSTN	0	0	-9999	-10000	0	0
PSENEN	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0	0	-9999	-10000	0	0
APH1A	0	0	-9999	-10000	0	0
NCAN	-0.04	0.15	-9999	-0.57	35	35
long-term memory	-0.001	0.017	-9999	-0.38	1	1
Syndecan-3/IL8	-0.011	0.059	-9999	-0.4	4	4
PSEN1	0	0	-9999	-10000	0	0
Src/Cortactin	0	0	-9999	-10000	0	0
FYN	-0.001	0.033	-9999	-0.74	1	1
limb bud formation	0	0	-9999	-10000	0	0
MC4R	-0.024	0.12	-9999	-0.57	21	21
SRC	0	0	-9999	-10000	0	0
PTN	-0.021	0.12	-9999	-0.7	15	15
FGFR/FGF/Syndecan-3	0	0	-9999	-10000	0	0
neuron projection morphogenesis	-0.027	0.082	-9999	-10000	0	0
Syndecan-3/AgRP	-0.19	0.2	-9999	-0.4	233	233
Syndecan-3/AgRP/MC4R	-0.19	0.2	-9999	-0.39	233	233
Fyn/Cortactin	-0.001	0.025	-9999	-0.56	1	1
SDC3	0	0	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.011	0.058	-9999	-0.4	4	4
IL8	-0.022	0.11	-9999	-0.61	18	18
Syndecan-3/Fyn/Cortactin	-0.001	0.017	-9999	-0.38	1	1
Syndecan-3/CASK	0	0	-9999	-10000	0	0
alpha-MSH/MC4R	-0.057	0.15	-9999	-0.43	67	67
Gamma Secretase	0	0	-9999	-10000	0	0

×

Reelin signaling pathway

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
CDK5R1/CDK5	-0.008	0.058	-9999	-0.42	10	10
VLDLR	-0.003	0.046	-9999	-0.74	2	2
CRKL	0	0	-9999	-10000	0	0
LRPAP1	0	0	-9999	-10000	0	0
FYN	-0.001	0.033	-9999	-0.74	1	1
ITGA3	-0.006	0.066	-9999	-0.74	4	4
RELN/VLDLR/Fyn	-0.086	0.19	-9999	-0.49	87	87
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.001	0.022	-9999	-10000	0	0
AKT1	-0.035	0.13	-9999	-0.49	3	3
MAP2K7	0	0	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0
DAB1	-0.033	0.13	-9999	-0.57	29	29
RELN/LRP8/DAB1	-0.098	0.18	-9999	-0.42	117	117
LRPAP1/LRP8	-0.002	0.032	-9999	-0.42	3	3
RELN/LRP8/DAB1/Fyn	-0.092	0.17	-9999	-0.43	88	88
DAB1/alpha3/beta1 Integrin	-0.085	0.16	-9999	-0.69	6	6
long-term memory	-0.12	0.19	-9999	-0.73	16	16
DAB1/LIS1	-0.085	0.16	-9999	-0.64	5	5
DAB1/CRLK/C3G	-0.082	0.15	-9999	-0.62	5	5
PIK3CA	0	0	-9999	-10000	0	0
DAB1/NCK2	-0.086	0.16	-9999	-0.64	5	5
ARHGEF2	0	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.065	0.2	-9999	-0.66	50	50
CDK5R1	-0.011	0.08	-9999	-0.57	10	10
RELN	-0.13	0.28	-9999	-0.73	89	89
PIK3R1	0	0	-9999	-10000	0	0
RELN/LRP8/Fyn	-0.087	0.18	-9999	-0.48	86	86
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.12	0.2	-9999	-0.45	106	106
MAPK8	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.097	0.18	-9999	-0.42	115	115
ITGB1	0	0	-9999	-10000	0	0
MAP1B	-0.092	0.17	-9999	-0.42	90	90
RELN/LRP8	-0.086	0.18	-9999	-0.48	86	86
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.094	0.17	-9999	-0.42	88	88
PI3K	0	0	-9999	-10000	0	0
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.004	0.049	-9999	-0.56	4	4
RAP1A	-0.076	0.14	-9999	-0.58	5	5
PAFAH1B1	0	0	-9999	-10000	0	0
MAPK8IP1	-0.003	0.042	-9999	-0.66	2	2
CRLK/C3G	0	0	-9999	-10000	0	0
GRIN2B	-0.006	0.057	-9999	-0.57	5	5
NCK2	0	0	-9999	-10000	0	0
neuron differentiation	-0.013	0.097	-9999	-0.4	3	3
neuron adhesion	-0.073	0.14	-9999	-0.62	5	5
LRP8	-0.003	0.044	-9999	-0.57	3	3
GSK3B	-0.026	0.12	-9999	-0.46	3	3
RELN/VLDLR/DAB1/Fyn	-0.091	0.17	-9999	-0.43	89	89
MAP3K11	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.065	0.12	-9999	-0.32	89	89
CDK5	0	0	-9999	-10000	0	0
MAPT	0.003	0.083	-9999	-0.66	7	7
neuron migration	-0.03	0.17	-9999	-0.55	6	6
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.043	0.082	-9999	-0.4	3	3
RELN/VLDLR	-0.079	0.17	-9999	-0.44	87	87

×

IL6-mediated signaling events

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
BCL2L1	-0.14	0.25	-10000	0	-0.75	13	13
CRP	-0.15	0.25	-10000	0	-0.77	13	13
cell cycle arrest	-0.17	0.28	-10000	0	-0.66	57	57
TIMP1	-0.11	0.21	-10000	0	-0.66	8	8
IL6ST	-0.018	0.14	-10000	0	-0.74	18	18
Rac1/GDP	-0.064	0.19	-10000	0	-0.69	21	21
AP1	-0.007	0.16	-10000	0	-0.55	15	15
GAB2	-0.004	0.12	-10000	0	-0.73	14	14
TNFSF11	-0.16	0.26	-10000	0	-0.67	35	35
HSP90B1	0	0.05	-10000	0	-10000	0	0
GAB1	0.014	0.008	-10000	0	-10000	0	0
MAPK14	-0.028	0.17	-10000	0	-0.72	17	17
AKT1	0.042	0.057	-10000	0	-10000	0	0
FOXO1	0.049	0.053	-10000	0	-10000	0	0
MAP2K6	-0.051	0.18	-10000	0	-0.75	17	17
mol:GTP	-0.002	0.003	-10000	0	-10000	0	0
MAP2K4	-0.075	0.2	-10000	0	-0.73	17	17
MITF	-0.069	0.19	-10000	0	-0.52	49	49
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0	0	-10000	0	-10000	0	0
A2M	-0.47	0.69	-10000	0	-1.5	165	165
CEBPB	0.016	0.004	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.029	0.12	0.22	30	-0.62	6	36
STAT3	-0.18	0.29	-10000	0	-0.69	57	57
STAT1	-0.007	0.016	-10000	0	-10000	0	0
CEBPD	-0.14	0.25	-10000	0	-0.82	13	13
PIK3CA	0.01	0.003	-10000	0	-10000	0	0
PI3K	0	0	-10000	0	-10000	0	0
JUN	0.006	0.005	-10000	0	-10000	0	0
PIAS3/MITF	-0.085	0.17	-10000	0	-0.63	25	25
MAPK11	-0.028	0.17	-10000	0	-0.72	17	17
STAT3 (dimer)/FOXO1	-0.19	0.31	-10000	0	-0.76	58	58
GRB2/SOS1/GAB family	-0.03	0.17	-10000	0	-0.67	19	19
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.051	0.19	-10000	0	-0.53	43	43
GRB2	0.014	0.008	-10000	0	-10000	0	0
JAK2	0	0	-10000	0	-10000	0	0
LBP	-0.11	0.21	-10000	0	-0.68	7	7
PIK3R1	0.008	0.005	-10000	0	-10000	0	0
JAK1	0.011	0.005	-10000	0	-10000	0	0
MYC	-0.14	0.25	-10000	0	-0.75	13	13
FGG	-0.48	0.57	-10000	0	-1.1	234	234
macrophage differentiation	-0.17	0.28	-10000	0	-0.66	57	57
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.089	0.2	-10000	0	-0.54	59	59
JUNB	-0.14	0.24	-10000	0	-0.74	14	14
FOS	-0.084	0.24	-10000	0	-0.74	61	61
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.07	0.19	-10000	0	-0.49	61	61
STAT1/PIAS1	-0.084	0.18	-10000	0	-0.49	50	50
GRB2/SOS1/GAB family/SHP2/PI3K	0.02	0.061	-10000	0	-0.31	1	1
STAT3 (dimer)	-0.18	0.29	-10000	0	-0.68	57	57
PRKCD	-0.09	0.22	-10000	0	-0.74	16	16
IL6R	-0.004	0.1	-10000	0	-0.74	10	10
SOCS3	-0.014	0.17	-10000	0	-0.84	10	10
gp130 (dimer)/JAK1/JAK1/LMO4	-0.011	0.092	-10000	0	-0.46	19	19
Rac1/GTP	-0.1	0.17	-10000	0	-0.7	21	21
HCK	-0.004	0.081	-10000	0	-0.74	6	6
MAPKKK cascade	0.044	0.13	-10000	0	-0.56	14	14
bone resorption	-0.15	0.25	-10000	0	-0.64	35	35
IRF1	-0.14	0.25	-10000	0	-0.75	13	13
mol:GDP	-0.065	0.19	-10000	0	-0.56	40	40
SOS1	0.015	0.013	-10000	0	-10000	0	0
VAV1	-0.068	0.2	-10000	0	-0.57	40	40
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.043	0.18	-10000	0	-0.81	17	17
PTPN11	-0.006	0.014	-10000	0	-10000	0	0
IL6/IL6RA	-0.098	0.23	-10000	0	-0.59	86	86
gp130 (dimer)/TYK2/TYK2/LMO4	-0.014	0.091	-10000	0	-0.47	19	19
gp130 (dimer)/JAK2/JAK2/LMO4	-0.014	0.091	-10000	0	-0.47	18	18
IL6	-0.11	0.28	-10000	0	-0.74	82	82
PIAS3	0	0	-10000	0	-10000	0	0
PTPRE	0.011	0.049	-10000	0	-0.73	2	2
PIAS1	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.075	0.18	-10000	0	-0.46	64	64
LMO4	0.007	0.029	-10000	0	-0.6	1	1
STAT3 (dimer)/PIAS3	-0.21	0.23	-10000	0	-0.66	57	57
MCL1	0.05	0.051	-10000	0	-10000	0	0

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	0.001	0.093	-10000	0	-0.59	12	12
NFATC2	-0.054	0.3	-10000	0	-0.73	72	72
NFATC3	0.013	0.054	-10000	0	-10000	0	0
CD40LG	-0.17	0.45	-10000	0	-1.1	70	70
ITCH	-0.008	0.11	-10000	0	-10000	0	0
CBLB	-0.008	0.11	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.14	0.28	-10000	0	-1	34	34
JUNB	-0.001	0.033	-10000	0	-0.74	1	1
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.053	0.12	-10000	0	-10000	0	0
T cell anergy	-0.061	0.18	-10000	0	-0.46	70	70
TLE4	-0.021	0.23	-10000	0	-0.74	27	27
Jun/NFAT1-c-4/p21SNFT	-0.12	0.27	-10000	0	-1.1	24	24
AP-1/NFAT1-c-4	-0.23	0.39	-10000	0	-1.3	39	39
IKZF1	-0.031	0.28	-10000	0	-1	24	24
T-helper 2 cell differentiation	-0.045	0.28	-10000	0	-0.88	36	36
AP-1/NFAT1	-0.14	0.24	-10000	0	-0.57	87	87
CALM1	-0.028	0.064	-10000	0	-10000	0	0
EGR2	-0.022	0.33	-10000	0	-1.4	17	17
EGR3	-0.024	0.33	-10000	0	-1.4	18	18
NFAT1/FOXP3	-0.09	0.21	-10000	0	-0.68	31	31
EGR1	-0.007	0.11	-10000	0	-0.74	11	11
JUN	0.003	0.022	-10000	0	-10000	0	0
EGR4	-0.005	0.086	-10000	0	-0.58	11	11
mol:Ca2+	-0.032	0.073	-10000	0	-10000	0	0
GBP3	-0.038	0.28	-10000	0	-0.89	32	32
FOSL1	-0.003	0.044	-10000	0	-0.57	3	3
NFAT1-c-4/MAF/IRF4	-0.099	0.27	-10000	0	-1.1	22	22
DGKA	-0.018	0.23	-10000	0	-0.76	22	22
CREM	0	0	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.14	0.3	-10000	0	-1.1	27	27
CTLA4	-0.017	0.21	-10000	0	-0.78	16	16
NFAT1-c-4 (dimer)/EGR1	-0.11	0.29	-10000	0	-1.2	23	23
NFAT1-c-4 (dimer)/EGR4	-0.11	0.27	-10000	0	-1.1	21	21
FOS	-0.088	0.25	-10000	0	-0.74	61	61
IFNG	-0.16	0.35	-10000	0	-1	51	51
T cell activation	-0.04	0.24	-10000	0	-0.84	17	17
MAF	0	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	-0.003	0.2	0.86	13	-10000	0	13
TNF	-0.037	0.3	-10000	0	-1	25	25
FASLG	-0.089	0.46	-10000	0	-1.6	36	36
TBX21	-0.062	0.23	-10000	0	-0.74	51	51
BATF3	0	0	-10000	0	-10000	0	0
PRKCQ	-0.059	0.22	-10000	0	-0.74	47	47
PTPN1	-0.018	0.23	-10000	0	-0.76	22	22
NFAT1-c-4/ICER1	-0.1	0.27	-10000	0	-1.1	22	22
GATA3	-0.023	0.13	-10000	0	-0.71	17	17
T-helper 1 cell differentiation	-0.15	0.34	-10000	0	-1	51	51
IL2RA	-0.15	0.28	-10000	0	-0.82	56	56
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.018	0.23	-10000	0	-0.76	22	22
E2F1	0.015	0.004	-10000	0	-10000	0	0
PPARG	-0.084	0.23	-10000	0	-0.74	57	57
SLC3A2	-0.018	0.23	-10000	0	-0.76	22	22
IRF4	-0.009	0.08	-10000	0	-0.74	6	6
PTGS2	-0.15	0.41	-10000	0	-1	58	58
CSF2	-0.14	0.41	-10000	0	-1.1	48	48
JunB/Fra1/NFAT1-c-4	-0.097	0.25	-10000	0	-1.1	21	21
IL4	-0.049	0.3	-10000	0	-0.93	36	36
IL5	-0.11	0.36	-10000	0	-1.1	35	35
IL2	-0.041	0.24	-10000	0	-0.88	16	16
IL3	-0.037	0.048	-10000	0	-10000	0	0
RNF128	-0.097	0.31	-10000	0	-0.8	81	81
NFATC1	0.002	0.2	-10000	0	-0.86	13	13
CDK4	0.008	0.16	0.66	7	-10000	0	7
PTPRK	-0.018	0.23	-10000	0	-0.7	28	28
IL8	-0.12	0.37	-10000	0	-1.1	37	37
POU2F1	0	0.003	-10000	0	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.012	0.081	-9999	-0.56	11	11
AKT1	-0.012	0.2	-9999	-0.65	28	28
PTK2B	-0.06	0.26	-9999	-0.89	31	31
VEGFR2 homodimer/Frs2	-0.12	0.27	-9999	-0.61	95	95
CAV1	-0.2	0.33	-9999	-0.74	137	137
CALM1	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.11	0.25	-9999	-0.93	28	28
endothelial cell proliferation	-0.009	0.2	-9999	-0.62	30	30
mol:Ca2+	-0.054	0.24	-9999	-0.84	28	28
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.1	0.23	-9999	-0.88	28	28
RP11-342D11.1	-0.061	0.24	-9999	-0.84	28	28
CDH5	-0.15	0.3	-9999	-0.74	102	102
VEGFA homodimer	0	0	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
SHC2	-0.004	0.057	-9999	-0.74	3	3
HRAS/GDP	-0.08	0.19	-9999	-0.71	28	28
SH2D2A	-0.001	0.033	-9999	-0.74	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.077	0.18	-9999	-0.67	29	29
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.11	0.25	-9999	-0.93	28	28
VEGFR1 homodimer	0	0	-9999	-10000	0	0
SHC/GRB2/SOS1	-0.09	0.21	-9999	-0.81	28	28
GRB10	-0.054	0.24	-9999	-0.84	28	28
PTPN11	0	0	-9999	-10000	0	0
GRB2	0	0	-9999	-10000	0	0
PAK1	-0.001	0.026	-9999	-0.57	1	1
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.17	0.32	-9999	-0.95	57	57
HRAS	0	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	-0.057	0.13	-9999	-0.46	31	31
HIF1A	0	0	-9999	-10000	0	0
FRS2	0	0	-9999	-10000	0	0
oxygen and reactive oxygen species metabolic process	-0.098	0.23	-9999	-0.86	28	28
mol:GTP	0	0	-9999	-10000	0	0
FLT4	-0.038	0.16	-9999	-0.74	26	26
Nck/Pak	-0.001	0.019	-9999	-0.42	1	1
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.11	0.25	-9999	-0.94	28	28
mol:GDP	-0.087	0.2	-9999	-0.77	28	28
mol:NADP	-0.01	0.18	-9999	-0.56	29	29
eNOS/Hsp90	-0.005	0.17	-9999	-0.52	29	29
PIK3R1	0	0	-9999	-10000	0	0
mol:IP3	-0.056	0.24	-9999	-0.86	28	28
HIF1A/ARNT	0	0	-9999	-10000	0	0
SHB	0	0	-9999	-10000	0	0
VEGFA	0	0	-9999	-10000	0	0
VEGFC	-0.003	0.046	-9999	-0.74	2	2
FAK1/Vinculin	-0.045	0.25	-9999	-0.85	31	31
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.11	0.26	-9999	-0.96	31	31
PTPN6	0	0	-9999	-10000	0	0
EPAS1	-0.13	0.29	-9999	-0.78	79	79
mol:L-citrulline	-0.01	0.18	-9999	-0.56	29	29
ITGAV	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.1	0.23	-9999	-0.88	28	28
VEGFR2 homodimer/VEGFA homodimer	-0.11	0.25	-9999	-0.94	28	28
VEGFR2/3 heterodimer	-0.14	0.31	-9999	-0.66	106	106
VEGFB	0	0	-9999	-10000	0	0
MAPK11	-0.053	0.25	-9999	-0.87	28	28
VEGFR2 homodimer	-0.11	0.31	-9999	-0.7	95	95
FLT1	0	0	-9999	-10000	0	0
NEDD4	-0.001	0.033	-9999	-0.74	1	1
MAPK3	-0.048	0.23	-9999	-0.78	30	30
MAPK1	-0.048	0.23	-9999	-0.78	30	30
VEGFA145/NRP2	-0.004	0.049	-9999	-0.56	4	4
VEGFR1/2 heterodimer	-0.12	0.27	-9999	-0.61	95	95
KDR	-0.11	0.31	-9999	-0.7	95	95
VEGFA165/NRP1/VEGFR2 homodimer	-0.099	0.24	-9999	-0.9	28	28
SRC	0	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	-0.049	0.24	-9999	-0.8	30	30
PI3K	-0.09	0.21	-9999	-0.82	28	28
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.11	0.25	-9999	-0.93	28	28
FES	-0.058	0.25	-9999	-0.89	28	28
GAB1	-0.094	0.22	-9999	-0.84	28	28
VEGFR2 homodimer/VEGFA homodimer/Src	-0.11	0.25	-9999	-0.93	28	28
CTNNB1	0	0	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
ARNT	0	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.095	0.24	-9999	-0.57	63	63
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.11	0.25	-9999	-0.93	28	28
PI3K/GAB1	-0.013	0.2	-9999	-0.67	28	28
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.096	0.22	-9999	-0.86	28	28
PRKACA	0	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.13	0.29	-9999	-0.61	106	106
HSP90AA1	0	0	-9999	-10000	0	0
CDC42	-0.057	0.25	-9999	-0.88	28	28
actin cytoskeleton reorganization	-0.11	0.24	-9999	-0.91	28	28
PTK2	-0.056	0.28	-9999	-0.95	31	31
EDG1	-0.061	0.24	-9999	-0.84	28	28
mol:DAG	-0.056	0.24	-9999	-0.86	28	28
CaM/Ca2+	-0.088	0.21	-9999	-0.78	28	28
MAP2K3	-0.046	0.24	-9999	-0.82	28	28
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.1	0.24	-9999	-0.89	28	28
PLCG1	-0.057	0.25	-9999	-0.88	28	28
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.1	0.23	-9999	-0.88	28	28
IQGAP1	0	0	-9999	-10000	0	0
YES1	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.11	0.25	-9999	-0.93	28	28
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.11	0.25	-9999	-0.93	28	28
cell migration	-0.041	0.24	-9999	-0.75	31	31
mol:PI-3-4-5-P3	-0.083	0.19	-9999	-0.73	28	28
FYN	-0.001	0.033	-9999	-0.74	1	1
VEGFB/NRP1	-0.091	0.21	-9999	-0.79	28	28
mol:NO	-0.01	0.18	-9999	-0.56	29	29
PXN	0	0	-9999	-10000	0	0
HRAS/GTP	-0.08	0.19	-9999	-0.71	28	28
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.1	0.24	-9999	-0.89	28	28
VHL	0	0	-9999	-10000	0	0
ITGB3	-0.016	0.11	-9999	-0.74	11	11
NOS3	-0.017	0.2	-9999	-0.65	29	29
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.11	0.25	-9999	-0.94	29	29
RAC1	0	0	-9999	-10000	0	0
PRKCA	-0.045	0.23	-9999	-0.8	29	29
PRKCB	-0.065	0.26	-9999	-0.89	29	29
VCL	0	0	-9999	-10000	0	0
VEGFA165/NRP1	-0.097	0.22	-9999	-0.85	28	28
VEGFR1/2 heterodimer/VEGFA homodimer	-0.11	0.25	-9999	-0.93	28	28
VEGFA165/NRP2	-0.004	0.049	-9999	-0.56	4	4
MAPKKK cascade	-0.08	0.19	-9999	-0.71	28	28
NRP2	-0.006	0.066	-9999	-0.74	4	4
VEGFC homodimer	-0.003	0.046	-9999	-0.74	2	2
NCK1	0	0	-9999	-10000	0	0
ROCK1	0	0	-9999	-10000	0	0
FAK1/Paxillin	-0.045	0.25	-9999	-0.85	31	31
MAP3K13	-0.057	0.25	-9999	-0.88	28	28
PDPK1	-0.014	0.19	-9999	-0.63	28	28

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.08	0.12	-10000	0	-0.52	19	19
epithelial cell differentiation	-0.036	0.1	-10000	0	-0.57	9	9
ITCH	0.023	0.027	-10000	0	-10000	0	0
WWP1	-0.038	0.088	-10000	0	-10000	0	0
FYN	-0.001	0.033	-10000	0	-0.74	1	1
EGFR	-0.023	0.12	-10000	0	-0.63	18	18
PRL	-0.009	0.072	-10000	0	-0.57	8	8
neuron projection morphogenesis	0.002	0.089	-10000	0	-10000	0	0
PTPRZ1	-0.38	0.27	-10000	0	-0.58	332	332
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.043	0.077	-10000	0	-0.48	7	7
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.057	0.097	-10000	0	-0.49	15	15
ADAM17	0.023	0.027	-10000	0	-10000	0	0
ErbB4/ErbB4	-0.058	0.11	-10000	0	-0.49	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.18	0.22	-10000	0	-0.53	131	131
NCOR1	0	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.053	0.091	-10000	0	-0.47	16	16
GRIN2B	-0.028	0.1	-10000	0	-0.52	8	8
ErbB4/ErbB2/betacellulin	-0.072	0.13	-10000	0	-0.48	38	38
STAT1	0	0	-10000	0	-10000	0	0
HBEGF	-0.026	0.14	-10000	0	-0.74	18	18
PRLR	-0.04	0.16	-10000	0	-0.63	32	32
E4ICDs/ETO2	-0.071	0.1	-10000	0	-0.6	8	8
axon guidance	0.054	0.073	-10000	0	-10000	0	0
NEDD4	0.021	0.042	-10000	0	-0.71	1	1
Prolactin receptor/Prolactin receptor/Prolactin	-0.036	0.13	-10000	0	-0.47	39	39
CBFA2T3	-0.012	0.092	-10000	0	-0.74	8	8
ErbB4/ErbB2/HBEGF	-0.056	0.093	-10000	0	-0.51	9	9
MAPK3	-0.038	0.071	-10000	0	-0.45	7	7
STAT1 (dimer)	-0.064	0.079	-10000	0	-0.42	1	1
MAPK1	-0.038	0.071	-10000	0	-0.45	7	7
JAK2	0	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.053	0.088	-10000	0	-0.46	15	15
NRG1	0.013	0.1	-10000	0	-0.56	15	15
NRG3	-0.19	0.32	-10000	0	-0.74	130	130
NRG2	-0.078	0.23	-10000	0	-0.74	53	53
NRG4	-0.07	0.19	-10000	0	-0.57	61	61
heart development	0.054	0.073	-10000	0	-10000	0	0
neural crest cell migration	-0.053	0.087	-10000	0	-0.45	15	15
ERBB2	0.029	0.032	-10000	0	-0.42	2	2
WWOX/E4ICDs	-0.064	0.079	-10000	0	-0.43	1	1
SHC1	0	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.1	0.14	-10000	0	-0.48	33	33
apoptosis	0.2	0.26	0.56	131	-10000	0	131
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.11	0.16	-10000	0	-0.53	53	53
ErbB4/ErbB2/epiregulin	-0.12	0.18	-10000	0	-0.51	56	56
ErbB4/ErbB4/betacellulin/betacellulin	-0.098	0.15	-10000	0	-0.55	38	38
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.085	0.14	-10000	0	-0.62	17	17
MDM2	-0.042	0.098	-10000	0	-0.43	1	1
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.041	0.081	-10000	0	-0.46	15	15
STAT5A	0.057	0.068	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.064	0.12	-10000	0	-0.53	20	20
DLG4	0	0	-10000	0	-10000	0	0
GRB2/SHC	0	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.058	0.072	-10000	0	-0.4	1	1
STAT5A (dimer)	-0.039	0.11	-10000	0	-0.63	9	9
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.045	0.068	-10000	0	-10000	0	0
LRIG1	-0.001	0.033	-10000	0	-0.74	1	1
EREG	-0.15	0.29	-10000	0	-0.72	104	104
BTC	-0.056	0.2	-10000	0	-0.74	38	38
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.054	0.074	-10000	0	-10000	0	0
ERBB4	-0.076	0.098	-10000	0	-0.49	1	1
STAT5B	0	0	-10000	0	-10000	0	0
YAP1	-0.02	0.025	-10000	0	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.077	0.11	-10000	0	-0.42	27	27
glial cell differentiation	0.058	0.072	0.4	1	-10000	0	1
WWOX	0	0	-10000	0	-10000	0	0
cell proliferation	-0.02	0.15	-10000	0	-0.6	12	12

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.015	0.042	-9999	-10000	0	0
BIRC5	-0.49	0.2	-9999	-0.57	426	426
NFKBIA	0.018	0.042	-9999	-10000	0	0
CPEB1	-0.05	0.18	-9999	-0.74	34	34
AKT1	0.018	0.042	-9999	-10000	0	0
NDEL1	0	0	-9999	-10000	0	0
Aurora A/BRCA1	0.014	0.037	-9999	-10000	0	0
NDEL1/TACC3	0.017	0.04	-9999	-10000	0	0
GADD45A	0	0	-9999	-10000	0	0
GSK3B	0.013	0.006	-9999	-10000	0	0
PAK1/Aurora A	0.015	0.045	-9999	-0.35	1	1
MDM2	-0.001	0.026	-9999	-0.57	1	1
JUB	0	0	-9999	-10000	0	0
TPX2	-0.28	0.2	-9999	-0.42	349	349
TP53	0.018	0.033	-9999	-0.35	1	1
DLG7	0.01	0.042	-9999	-10000	0	0
AURKAIP1	0	0	-9999	-10000	0	0
ARHGEF7	0	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	0.018	0.043	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.014	0.037	-9999	-10000	0	0
AURKA	0.016	0.052	-9999	-10000	0	0
AURKB	-0.088	0.051	-9999	-0.16	23	23
CDC25B	0.019	0.036	-9999	-10000	0	0
G2/M transition checkpoint	0.014	0.037	-9999	-10000	0	0
mRNA polyadenylation	-0.018	0.12	-9999	-0.44	34	34
Aurora A/CPEB	-0.018	0.12	-9999	-0.44	34	34
Aurora A/TACC1/TRAP/chTOG	0.022	0.045	-9999	-0.4	2	2
BRCA1	0	0	-9999	-10000	0	0
centrosome duplication	0.015	0.045	-9999	-0.35	1	1
regulation of centrosome cycle	0.017	0.04	-9999	-10000	0	0
spindle assembly	0.015	0.044	-9999	-0.4	2	2
TDRD7	0	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.24	0.1	-9999	-0.42	24	24
CENPA	-0.076	0.043	-9999	-0.18	23	23
Aurora A/PP2A	0.015	0.042	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.028	0.033	-9999	-10000	0	0
negative regulation of DNA binding	0.018	0.033	-9999	-0.35	1	1
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0	0	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
Ajuba/Aurora A	0.014	0.037	-9999	-10000	0	0
mitotic prometaphase	0.025	0.017	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.016	0.052	-9999	-10000	0	0
TACC1	-0.003	0.046	-9999	-0.74	2	2
TACC3	-0.002	0.036	-9999	-0.57	2	2
Aurora A/Antizyme1	0.02	0.038	-9999	-10000	0	0
Aurora A/RasGAP	0.015	0.042	-9999	-10000	0	0
OAZ1	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.013	0.006	-9999	-10000	0	0
GIT1	0	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	-0.001	0.015	-9999	-0.35	1	1
Importin alpha/Importin beta/TPX2	-0.28	0.2	-9999	-0.42	349	349
PPP2R5D	0	0	-9999	-10000	0	0
Aurora A/TPX2	-0.22	0.16	-9999	-0.46	24	24
PAK1	-0.001	0.026	-9999	-0.57	1	1
CKAP5	0	0	-9999	-10000	0	0

×

Wnt 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
Noncanonical Wnts/FZD	-0.045	0.091	-9999	-0.34	25	25
FZD6	0	0	-9999	-10000	0	0
WNT6	-0.094	0.21	-9999	-0.57	82	82
WNT4	-0.01	0.083	-9999	-0.66	8	8
FZD3	0	0	-9999	-10000	0	0
WNT5A	-0.014	0.093	-9999	-0.6	12	12
WNT11	-0.038	0.16	-9999	-0.68	28	28

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.065	0.1	-10000	0	-0.36	5	5
NT3 (dimer)/TRKC	-0.17	0.26	-10000	0	-0.56	153	153
NT3 (dimer)/TRKB	-0.12	0.19	-10000	0	-0.4	156	156
SHC/Grb2/SOS1/GAB1/PI3K	0	0	-10000	0	-10000	0	0
RAPGEF1	0	0	-10000	0	-10000	0	0
BDNF	-0.093	0.24	-10000	0	-0.74	63	63
PIK3CA	0	0	-10000	0	-10000	0	0
DYNLT1	0	0	-10000	0	-10000	0	0
NTRK1	-0.007	0.073	-10000	0	-0.74	5	5
NTRK2	-0.14	0.26	-10000	0	-0.62	112	112
NTRK3	-0.22	0.34	-10000	0	-0.73	148	148
NT-4/5 (dimer)/TRKB	-0.12	0.19	-10000	0	-0.39	156	156
neuron apoptosis	0.13	0.19	0.46	91	-10000	0	91
SHC 2-3/Grb2	-0.14	0.21	-10000	0	-0.51	91	91
SHC1	0	0	-10000	0	-10000	0	0
SHC2	-0.056	0.1	-10000	0	-0.44	16	16
SHC3	-0.16	0.26	-10000	0	-0.66	96	96
STAT3 (dimer)	-0.005	0.042	-10000	0	-0.37	6	6
NT3 (dimer)/TRKA	-0.043	0.12	-10000	0	-0.37	57	57
RIN/GDP	-0.045	0.092	-10000	0	-0.27	2	2
GIPC1	0	0	-10000	0	-10000	0	0
KRAS	0	0	-10000	0	-10000	0	0
DNAJA3	-0.024	0.07	-10000	0	-0.46	3	3
RIN/GTP	0	0	-10000	0	-10000	0	0
CCND1	0.014	0.11	-10000	0	-0.88	7	7
MAGED1	0	0	-10000	0	-10000	0	0
PTPN11	0	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.012	0.092	-10000	0	-0.74	8	8
SHC/GRB2/SOS1	0	0	-10000	0	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.035	0.12	-10000	0	-0.47	38	38
TRKA/NEDD4-2	-0.006	0.055	-10000	0	-0.56	5	5
ELMO1	-0.013	0.098	-10000	0	-0.74	9	9
RhoG/GTP/ELMO1/DOCK1	-0.009	0.064	-10000	0	-0.48	9	9
NGF	-0.02	0.12	-10000	0	-0.7	14	14
HRAS	0	0	-10000	0	-10000	0	0
DOCK1	0	0	-10000	0	-10000	0	0
GAB2	-0.021	0.12	-10000	0	-0.74	14	14
RIT2	0	0	-10000	0	-10000	0	0
RIT1	0	0	-10000	0	-10000	0	0
FRS2	0	0	-10000	0	-10000	0	0
DNM1	-0.002	0.036	-10000	0	-0.57	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.03	0.085	-10000	0	-0.41	12	12
mol:GDP	-0.067	0.13	-10000	0	-0.4	3	3
NGF (dimer)	-0.02	0.12	-10000	0	-0.7	14	14
RhoG/GDP	-0.01	0.075	-10000	0	-0.56	9	9
RIT1/GDP	-0.041	0.092	-10000	0	-0.28	1	1
TIAM1	-0.001	0.033	-10000	0	-0.74	1	1
PIK3R1	0	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.14	0.23	-10000	0	-0.45	161	161
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0	0	-10000	0	-10000	0	0
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.013	0.093	-10000	0	-0.7	9	9
RAP1/GDP	-0.047	0.067	-10000	0	-10000	0	0
KIDINS220/CRKL	0	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.093	0.24	-10000	0	-0.74	63	63
ubiquitin-dependent protein catabolic process	-0.017	0.087	-10000	0	-0.45	19	19
Schwann cell development	-0.054	0.036	-10000	0	-10000	0	0
EHD4	0	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	-0.007	0.041	-10000	0	-10000	0	0
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
CDC42/GTP	-0.22	0.27	-10000	0	-0.72	77	77
ABL1	0	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
Rap1/GTP	-0.049	0.076	-10000	0	-10000	0	0
STAT3	-0.005	0.042	-10000	0	-0.37	6	6
axon guidance	-0.21	0.25	-10000	0	-0.68	77	77
MAPK3	-0.005	0.12	-10000	0	-0.43	35	35
MAPK1	-0.005	0.12	-10000	0	-0.43	35	35
CDC42/GDP	-0.041	0.092	-10000	0	-0.28	1	1
NTF3	-0.013	0.094	-10000	0	-0.7	9	9
NTF4	-0.012	0.092	-10000	0	-0.74	8	8
NGF (dimer)/TRKA/FAIM	-0.017	0.088	-10000	0	-0.46	19	19
PI3K	0	0	-10000	0	-10000	0	0
FRS3	0	0	-10000	0	-10000	0	0
FAIM	0	0	-10000	0	-10000	0	0
GAB1	0	0	-10000	0	-10000	0	0
RASGRF1	-0.27	0.2	-10000	0	-0.42	311	311
SOS1	0	0	-10000	0	-10000	0	0
MCF2L	-0.13	0.24	-10000	0	-0.49	150	150
RGS19	0	0	-10000	0	-10000	0	0
CDC42	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.055	0.081	-10000	0	-10000	0	0
Rac1/GDP	-0.041	0.092	-10000	0	-0.27	2	2
NGF (dimer)/TRKA/GRIT	-0.018	0.089	-10000	0	-0.46	19	19
neuron projection morphogenesis	0.003	0.075	-10000	0	-0.47	1	1
NGF (dimer)/TRKA/NEDD4-2	-0.017	0.088	-10000	0	-0.46	19	19
MAP2K1	0.035	0	-10000	0	-10000	0	0
NGFR	-0.049	0.16	-10000	0	-0.57	43	43
NGF (dimer)/TRKA/GIPC/GAIP	-0.011	0.055	-10000	0	-10000	0	0
RAS family/GTP/PI3K	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	0	0	-10000	0	-10000	0	0
NRAS	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
PRKCI	0	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.048	0.12	-10000	0	-0.66	16	16
RASA1	0	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.006	0.055	-10000	0	-0.56	5	5
SQSTM1	0	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.13	0.21	-10000	0	-0.5	83	83
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.015	0.074	-10000	0	-0.4	16	16
MATK	-0.028	0.14	-10000	0	-0.74	19	19
NEDD4L	0	0	-10000	0	-10000	0	0
RAS family/GDP	-0.043	0.064	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.026	0.076	-10000	0	-0.34	16	16
Rac1/GTP	-0.17	0.13	-10000	0	-0.32	143	143
FRS2 family/SHP2/CRK family	0	0	-10000	0	-10000	0	0

×

Regulation 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.02	0	-9999	-10000	0	0
SMARCC1	0.006	0.008	-9999	-10000	0	0
REL	0	0.002	-9999	-10000	0	0
HDAC7	-0.029	0.12	-9999	-10000	0	0
JUN	0.001	0.004	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
KAT2B	-0.001	0.033	-9999	-0.74	1	1
KAT5	0	0.001	-9999	-10000	0	0
MAPK14	0.012	0.026	-9999	-0.45	1	1
FOXO1	0	0	-9999	-10000	0	0
T-DHT/AR	-0.036	0.13	-9999	-0.44	1	1
MAP2K6	0.006	0.028	-9999	-0.6	1	1
BRM/BAF57	-0.001	0.025	-9999	-0.56	1	1
MAP2K4	0.007	0.007	-9999	-10000	0	0
SMARCA2	0	0.033	-9999	-0.74	1	1
PDE9A	-0.11	0.23	-9999	-0.85	28	28
NCOA2	0.005	0.034	-9999	-0.74	1	1
CEBPA	-0.001	0.033	-9999	-0.74	1	1
EHMT2	0.001	0.004	-9999	-10000	0	0
cell proliferation	-0.047	0.17	-9999	-0.52	24	24
NR0B1	-0.18	0.27	-9999	-0.57	161	161
EGR1	-0.015	0.11	-9999	-0.74	11	11
RXRs/9cRA	-0.23	0.22	-9999	-0.44	265	265
AR/RACK1/Src	-0.014	0.074	-9999	-10000	0	0
AR/GR	-0.063	0.12	-9999	-0.34	42	42
GNB2L1	0.005	0.005	-9999	-10000	0	0
PKN1	0	0	-9999	-10000	0	0
RCHY1	0	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0.002	-9999	-10000	0	0
MAPK8	0.013	0.016	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.013	0.074	-9999	-0.45	1	1
SRC	0.018	0.04	-9999	-10000	0	0
NR3C1	0	0	-9999	-10000	0	0
KLK3	-0.13	0.15	-9999	-0.55	27	27
APPBP2	0.008	0.006	-9999	-10000	0	0
TRIM24	0.001	0.004	-9999	-10000	0	0
T-DHT/AR/TIP60	-0.037	0.053	-9999	-10000	0	0
TMPRSS2	-0.42	0.57	-9999	-1.2	161	161
RXRG	-0.39	0.37	-9999	-0.74	265	265
mol:9cRA	0	0	-9999	-10000	0	0
RXRA	0	0	-9999	-10000	0	0
RXRB	0	0	-9999	-10000	0	0
CARM1	0.006	0.005	-9999	-10000	0	0
NR2C2	0	0	-9999	-10000	0	0
KLK2	-0.019	0.13	-9999	-0.48	3	3
AR	-0.052	0.15	-9999	-0.33	103	103
SENP1	0	0	-9999	-10000	0	0
HSP90AA1	0	0	-9999	-10000	0	0
MDM2	-0.001	0.026	-9999	-0.57	1	1
SRY	-0.005	0.051	-9999	-0.57	4	4
GATA2	-0.081	0.23	-9999	-0.74	55	55
MYST2	0	0.001	-9999	-10000	0	0
HOXB13	-0.34	0.28	-9999	-0.57	294	294
T-DHT/AR/RACK1/Src	-0.014	0.07	-9999	-10000	0	0
positive regulation of transcription	-0.081	0.23	-9999	-0.74	55	55
DNAJA1	0.008	0.006	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0.006	-9999	-10000	0	0
NCOA1	0.014	0.004	-9999	-10000	0	0
SPDEF	-0.096	0.25	-9999	-0.73	67	67
T-DHT/AR/TIF2	0.013	0.056	-9999	-10000	0	0
T-DHT/AR/Hsp90	-0.037	0.053	-9999	-10000	0	0
GSK3B	0.007	0.006	-9999	-10000	0	0
NR2C1	0	0.001	-9999	-10000	0	0
mol:T-DHT	0.012	0.043	-9999	-0.38	1	1
SIRT1	0	0	-9999	-10000	0	0
ZMIZ2	0	0.002	-9999	-10000	0	0
POU2F1	-0.001	0.042	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.13	0.15	-9999	-0.47	24	24
CREBBP	0	0	-9999	-10000	0	0
SMARCE1	0.001	0.004	-9999	-10000	0	0

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0	0	-9999	-10000	0	0
CCL5	-0.013	0.098	-9999	-0.74	9	9
SDCBP	0	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.09	0.1	-9999	-0.43	4	4
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.093	0.079	-9999	-0.4	5	5
Syndecan-1/Syntenin	-0.092	0.078	-9999	-0.4	4	4
MAPK3	-0.059	0.087	-9999	-0.48	1	1
HGF/MET	-0.12	0.23	-9999	-0.56	111	111
TGFB1/TGF beta receptor Type II	0	0	-9999	-10000	0	0
BSG	0	0	-9999	-10000	0	0
keratinocyte migration	-0.092	0.078	-9999	-0.39	5	5
Syndecan-1/RANTES	-0.1	0.1	-9999	-0.52	12	12
Syndecan-1/CD147	-0.084	0.072	-9999	-0.43	2	2
Syndecan-1/Syntenin/PIP2	-0.089	0.075	-9999	-0.39	4	4
LAMA5	-0.001	0.033	-9999	-0.74	1	1
positive regulation of cell-cell adhesion	-0.087	0.074	-9999	-0.38	4	4
MMP7	-0.039	0.15	-9999	-0.62	31	31
HGF	-0.16	0.3	-9999	-0.74	108	108
Syndecan-1/CASK	-0.086	0.094	-9999	-0.41	4	4
Syndecan-1/HGF/MET	-0.17	0.17	-9999	-0.54	61	61
regulation of cell adhesion	-0.05	0.086	-9999	-0.46	1	1
HPSE	0	0	-9999	-10000	0	0
positive regulation of cell migration	-0.09	0.1	-9999	-0.43	4	4
SDC1	-0.09	0.1	-9999	-0.43	4	4
Syndecan-1/Collagen	-0.09	0.1	-9999	-0.43	4	4
PPIB	0	0	-9999	-10000	0	0
MET	-0.004	0.053	-9999	-0.68	3	3
PRKACA	0	0	-9999	-10000	0	0
MMP9	-0.032	0.13	-9999	-0.57	28	28
MAPK1	-0.059	0.087	-9999	-0.48	1	1
homophilic cell adhesion	-0.089	0.1	-9999	-0.42	4	4
MMP1	-0.36	0.28	-9999	-0.57	310	310

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.12	0.39	-9999	-1.2	51	51
MKNK1	0	0	-9999	-10000	0	0
MAPK14	-0.036	0.12	-9999	-0.43	8	8
ATF2/c-Jun	-0.01	0.098	-9999	-0.43	3	3
MAPK11	-0.036	0.12	-9999	-0.43	8	8
MITF	-0.041	0.16	-9999	-0.37	86	86
MAPKAPK5	-0.032	0.15	-9999	-0.53	8	8
KRT8	-0.032	0.15	-9999	-0.53	8	8
MAPKAPK3	0	0	-9999	-10000	0	0
MAPKAPK2	0	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.054	0.18	-9999	-0.46	75	75
CEBPB	-0.032	0.15	-9999	-0.36	75	75
SLC9A1	-0.032	0.15	-9999	-0.53	8	8
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.026	0.15	-9999	-0.52	8	8
p38alpha-beta/MNK1	-0.065	0.13	-9999	-0.58	8	8
JUN	-0.009	0.098	-9999	-0.42	3	3
PPARGC1A	-0.13	0.28	-9999	-0.49	151	151
USF1	-0.032	0.15	-9999	-0.53	8	8
RAB5/GDP/GDI1	-0.045	0.095	-9999	-0.4	8	8
NOS2	-0.097	0.32	-9999	-1.2	32	32
DDIT3	-0.032	0.15	-9999	-0.36	75	75
RAB5A	0	0	-9999	-10000	0	0
HSPB1	-0.018	0.12	-9999	-0.44	8	8
p38alpha-beta/HBP1	-0.065	0.13	-9999	-0.58	8	8
CREB1	-0.03	0.15	-9999	-0.38	75	75
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	-0.021	0.13	-9999	-0.52	8	8
RPS6KA4	-0.032	0.15	-9999	-0.53	8	8
PLA2G4A	-0.025	0.14	-9999	-0.53	13	13
GDI1	-0.032	0.15	-9999	-0.53	8	8
TP53	-0.044	0.19	-9999	-0.7	9	9
RPS6KA5	-0.032	0.15	-9999	-0.53	8	8
ESR1	-0.055	0.2	-9999	-0.6	31	31
HBP1	0	0	-9999	-10000	0	0
MEF2C	-0.044	0.18	-9999	-0.57	21	21
MEF2A	-0.032	0.15	-9999	-0.53	8	8
EIF4EBP1	-0.032	0.16	-9999	-0.51	10	10
KRT19	-0.038	0.17	-9999	-0.69	12	12
ELK4	-0.032	0.15	-9999	-0.36	75	75
ATF6	-0.032	0.15	-9999	-0.53	8	8
ATF1	-0.03	0.15	-9999	-0.54	8	8
p38alpha-beta/MAPKAPK2	-0.065	0.13	-9999	-0.58	8	8
p38alpha-beta/MAPKAPK3	-0.065	0.13	-9999	-0.58	8	8

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	-0.007	0.06	-9999	-0.56	6	6
Necdin/E2F1	-0.009	0.07	-9999	-0.56	8	8
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.04	0.11	-9999	-0.45	17	17
NGF (dimer)/p75(NTR)/BEX1	-0.099	0.2	-9999	-0.45	111	111
NT-4/5 (dimer)/p75(NTR)	-0.044	0.13	-9999	-0.44	51	51
IKBKB	-0.001	0.026	-9999	-0.57	1	1
AKT1	-0.004	0.12	-9999	-0.48	11	11
IKBKG	0	0	-9999	-10000	0	0
BDNF	-0.093	0.24	-9999	-0.74	63	63
MGDIs/NGR/p75(NTR)/LINGO1	-0.061	0.14	-9999	-0.38	82	82
FURIN	0	0	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.095	0.19	-9999	-0.45	105	105
LINGO1	-0.051	0.16	-9999	-0.57	44	44
Sortilin/TRAF6/NRIF	-0.004	0.038	-9999	-10000	0	0
proBDNF (dimer)	-0.093	0.24	-9999	-0.74	63	63
NTRK1	-0.007	0.073	-9999	-0.74	5	5
RTN4R	-0.003	0.042	-9999	-0.66	2	2
neuron apoptosis	-0.031	0.16	-9999	-0.56	13	13
IRAK1	0	0	-9999	-10000	0	0
SHC1	-0.021	0.13	-9999	-0.56	11	11
ARHGDIA	0	0	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
Gamma Secretase	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.043	0.12	-9999	-0.48	17	17
MAGEH1	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.05	0.13	-9999	-0.49	24	24
Mammalian IAPs/DIABLO	-0.005	0.047	-9999	-0.43	6	6
proNGF (dimer)	-0.02	0.12	-9999	-0.7	14	14
MAGED1	0	0	-9999	-10000	0	0
APP	0	0	-9999	-10000	0	0
NT-4/5 (dimer)	-0.012	0.092	-9999	-0.74	8	8
ZNF274	0	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	-0.035	0.11	-9999	-0.48	11	11
NGF	-0.02	0.12	-9999	-0.7	14	14
cell cycle arrest	-0.023	0.14	-9999	-0.45	17	17
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.02	0.064	-9999	-0.47	3	3
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.037	0.11	-9999	-0.37	51	51
NCSTN	0	0	-9999	-10000	0	0
mol:GTP	-0.042	0.13	-9999	-0.39	54	54
PSENEN	0	0	-9999	-10000	0	0
mol:ceramide	-0.017	0.13	-9999	-0.48	17	17
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.015	0.049	-9999	-0.37	3	3
p75(NTR)/beta APP	-0.036	0.12	-9999	-0.42	43	43
BEX1	-0.091	0.23	-9999	-0.68	67	67
mol:GDP	-0.029	0.13	-9999	-0.4	54	54
NGF (dimer)	-0.036	0.12	-9999	-0.51	19	19
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.055	0.13	-9999	-0.63	7	7
PIK3R1	0	0	-9999	-10000	0	0
RAC1/GTP	-0.036	0.11	-9999	-0.34	54	54
MYD88	0	0	-9999	-10000	0	0
CHUK	0	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.042	0.13	-9999	-0.39	54	54
RHOB	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
MAGE-G1/E2F1	0	0	-9999	-10000	0	0
NT3 (dimer)	-0.013	0.093	-9999	-0.7	9	9
TP53	-0.075	0.15	-9999	-0.67	7	7
PRDM4	-0.017	0.13	-9999	-0.48	17	17
BDNF (dimer)	-0.27	0.24	-9999	-0.65	86	86
PIK3CA	0	0	-9999	-10000	0	0
SORT1	-0.009	0.08	-9999	-0.74	6	6
activation of caspase activity	-0.039	0.11	-9999	-0.45	17	17
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.043	0.12	-9999	-0.48	17	17
RHOC	0	0	-9999	-10000	0	0
XIAP	0	0	-9999	-10000	0	0
MAPK10	-0.014	0.14	-9999	-0.5	15	15
DIABLO	0	0	-9999	-10000	0	0
SMPD2	-0.017	0.13	-9999	-0.48	17	17
APH1B	0	0	-9999	-10000	0	0
APH1A	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.048	0.14	-9999	-0.4	60	60
PSEN1	0	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-9999	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.045	0.13	-9999	-0.43	52	52
MAPK8	-0.01	0.14	-9999	-0.49	13	13
MAPK9	-0.01	0.14	-9999	-0.49	13	13
APAF1	0	0	-9999	-10000	0	0
NTF3	-0.013	0.094	-9999	-0.7	9	9
NTF4	-0.012	0.092	-9999	-0.74	8	8
NDN	-0.012	0.092	-9999	-0.74	8	8
RAC1/GDP	0	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.032	0.097	-9999	-0.65	3	3
p75 CTF/Sortilin/TRAF6/NRIF	-0.005	0.047	-9999	-0.43	6	6
RhoA-B-C/GTP	-0.042	0.12	-9999	-0.39	54	54
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.08	0.16	-9999	-0.43	68	68
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.086	0.17	-9999	-0.46	68	68
PRKACB	0	0	-9999	-10000	0	0
proBDNF (dimer)/p75 ECD	-0.07	0.18	-9999	-0.56	63	63
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.009	0.08	-9999	-0.74	6	6
BIRC2	0	0	-9999	-10000	0	0
neuron projection morphogenesis	-0.015	0.13	-9999	-0.46	16	16
BAD	-0.003	0.14	-9999	-0.54	7	7
RIPK2	0	0	-9999	-10000	0	0
NGFR	-0.049	0.16	-9999	-0.57	43	43
CYCS	-0.009	0.12	-9999	-0.45	17	17
ADAM17	0	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.038	0.11	-9999	-0.51	11	11
BCL2L11	-0.003	0.14	-9999	-0.54	7	7
BDNF (dimer)/p75(NTR)	-0.1	0.22	-9999	-0.52	100	100
PI3K	-0.038	0.11	-9999	-0.51	11	11
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.043	0.12	-9999	-0.48	17	17
NDNL2	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
PRKCI	0	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)	-0.05	0.15	-9999	-0.46	54	54
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.043	0.12	-9999	-0.48	17	17
TRAF6	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
PRKCZ	0	0	-9999	-10000	0	0
PLG	-0.006	0.057	-9999	-0.57	5	5
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.084	0.17	-9999	-0.43	76	76
SQSTM1	0	0	-9999	-10000	0	0
NGFRAP1	0	0	-9999	-10000	0	0
CASP3	0	0.13	-9999	-0.49	7	7
E2F1	0	0	-9999	-10000	0	0
CASP9	0	0	-9999	-10000	0	0
IKK complex	-0.019	0.075	-9999	-0.51	3	3
NGF (dimer)/TRKA	-0.02	0.1	-9999	-0.53	19	19
MMP7	-0.039	0.15	-9999	-0.62	31	31
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.04	0.11	-9999	-0.45	17	17
MMP3	-0.34	0.28	-9999	-0.57	300	300
APAF-1/Caspase 9	-0.031	0.087	-9999	-0.54	4	4

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	-0.25	0.35	-9999	-0.74	168	168
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0	0	-9999	-10000	0	0
TCEB1	0	0	-9999	-10000	0	0
HIF1A/p53	-0.01	0.03	-9999	-0.46	1	1
HIF1A	-0.011	0.026	-9999	-10000	0	0
COPS5	0	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0	0	-9999	-10000	0	0
FIH (dimer)	0	0	-9999	-10000	0	0
CDKN2A	-0.27	0.29	-9999	-0.58	233	233
ARNT/IPAS	-0.19	0.26	-9999	-0.56	168	168
HIF1AN	0	0	-9999	-10000	0	0
GNB2L1	0	0	-9999	-10000	0	0
HIF1A/ARNT	-0.009	0.022	-9999	-10000	0	0
CUL2	0	0	-9999	-10000	0	0
OS9	0	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	0	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	-0.009	0.022	-9999	-10000	0	0
PHD1-3/OS9	-0.047	0.11	-9999	-10000	0	0
HIF1A/RACK1/Elongin B/Elongin C	-0.007	0.017	-9999	-10000	0	0
VHL	0	0	-9999	-10000	0	0
HSP90AA1	0	0	-9999	-10000	0	0
HIF1A/JAB1	-0.009	0.022	-9999	-10000	0	0
EGLN3	-0.087	0.21	-9999	-0.57	76	76
EGLN2	0	0	-9999	-10000	0	0
EGLN1	0	0	-9999	-10000	0	0
TP53	-0.001	0.033	-9999	-0.74	1	1
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0	0	-9999	-10000	0	0
ARNT	0	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.14	0.14	-9999	-0.36	39	39

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	0	0.13	-10000	0	-0.38	28	28
TBX21	-0.093	0.5	-10000	0	-1.4	57	57
B2M	0.006	0.058	-10000	0	-0.74	3	3
TYK2	0.016	0.017	-10000	0	-10000	0	0
IL12RB1	-0.033	0.19	-10000	0	-0.77	32	32
GADD45B	-0.028	0.36	-10000	0	-1.2	34	34
IL12RB2	-0.046	0.18	-10000	0	-0.57	54	54
GADD45G	-0.015	0.33	-10000	0	-1.1	28	28
natural killer cell activation	0.006	0.019	-10000	0	-10000	0	0
RELB	-0.001	0.026	-10000	0	-0.57	1	1
RELA	0	0	-10000	0	-10000	0	0
IL18	0.009	0.059	-10000	0	-0.75	3	3
IL2RA	-0.008	0.072	-10000	0	-0.66	6	6
IFNG	-0.008	0.075	-10000	0	-0.68	6	6
STAT3 (dimer)	-0.003	0.29	-10000	0	-0.84	34	34
HLA-DRB5	-0.062	0.22	-10000	0	-0.74	48	48
FASLG	-0.047	0.41	-10000	0	-1.2	40	40
NF kappa B2 p52/RelB	-0.13	0.3	-10000	0	-1	38	38
CD4	-0.013	0.13	-10000	0	-0.74	15	15
SOCS1	-0.001	0.033	-10000	0	-0.74	1	1
EntrezGene:6955	-0.001	0.01	-10000	0	-10000	0	0
CD3D	-0.006	0.11	-10000	0	-0.74	11	11
CD3E	-0.003	0.1	-10000	0	-0.74	9	9
CD3G	-0.037	0.18	-10000	0	-0.74	32	32
IL12Rbeta2/JAK2	-0.02	0.14	-10000	0	-0.41	54	54
CCL3	-0.027	0.35	-10000	0	-1.1	32	32
CCL4	-0.03	0.36	-10000	0	-1.1	37	37
HLA-A	0.009	0.034	-10000	0	-0.74	1	1
IL18/IL18R	0.019	0.14	-10000	0	-0.57	25	25
NOS2	-0.077	0.44	-10000	0	-1.3	48	48
IL12/IL12R/TYK2/JAK2/SPHK2	0.001	0.13	-10000	0	-0.37	31	31
IL1R1	-0.025	0.34	-10000	0	-1.1	29	29
IL4	-0.004	0.019	-10000	0	-10000	0	0
JAK2	0.016	0.017	-10000	0	-10000	0	0
EntrezGene:6957	-0.001	0.009	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.03	0.31	-10000	0	-1.1	26	26
RAB7A	0.01	0.28	-10000	0	-0.83	28	28
lysosomal transport	0.014	0.26	-10000	0	-0.78	28	28
FOS	-0.16	0.5	-10000	0	-1.3	82	82
STAT4 (dimer)	-0.006	0.34	-10000	0	-0.99	36	36
STAT5A (dimer)	-0.13	0.3	-10000	0	-1	40	40
GZMA	-0.033	0.37	-10000	0	-1.2	30	30
GZMB	-0.033	0.37	-10000	0	-1.1	36	36
HLX	0	0	-10000	0	-10000	0	0
LCK	-0.036	0.39	-10000	0	-1.1	38	38
TCR/CD3/MHC II/CD4	-0.089	0.33	-10000	0	-0.9	50	50
IL2/IL2R	-0.013	0.1	-10000	0	-0.69	8	8
MAPK14	-0.012	0.34	-10000	0	-1	34	34
CCR5	-0.023	0.35	-10000	0	-1.2	27	27
IL1B	-0.001	0.12	-10000	0	-0.76	11	11
STAT6	0.018	0.1	-10000	0	-10000	0	0
STAT4	-0.012	0.092	-10000	0	-0.74	8	8
STAT3	0	0	-10000	0	-10000	0	0
STAT1	0	0	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
NFKB2	0	0	-10000	0	-10000	0	0
IL12B	0.017	0.016	-10000	0	-10000	0	0
CD8A	0	0.088	-10000	0	-0.74	7	7
CD8B	-0.013	0.13	-10000	0	-0.7	17	17
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0	0.13	0.38	28	-10000	0	28
IL2RB	-0.004	0.057	-10000	0	-0.74	3	3
proteasomal ubiquitin-dependent protein catabolic process	0.003	0.3	-10000	0	-0.87	36	36
IL2RG	-0.01	0.087	-10000	0	-0.74	7	7
IL12	0.017	0.08	-10000	0	-0.57	8	8
STAT5A	0	0	-10000	0	-10000	0	0
CD247	-0.008	0.12	-10000	0	-0.74	12	12
IL2	0	0	-10000	0	-10000	0	0
SPHK2	0	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.004	0.098	-10000	0	-0.75	8	8
IL12/IL12R/TYK2/JAK2	-0.051	0.44	-10000	0	-1.3	39	39
MAP2K3	-0.016	0.34	-10000	0	-1	35	35
RIPK2	0	0	-10000	0	-10000	0	0
MAP2K6	-0.016	0.34	-10000	0	-1	35	35
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.059	0.22	-10000	0	-0.74	46	46
IL18RAP	-0.018	0.15	-10000	0	-0.75	21	21
IL12Rbeta1/TYK2	-0.015	0.15	-10000	0	-0.59	32	32
EOMES	-0.028	0.23	-10000	0	-1.4	13	13
STAT1 (dimer)	-0.001	0.29	-10000	0	-0.84	32	32
T cell proliferation	0.008	0.25	-10000	0	-0.71	33	33
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.006	0.076	-10000	0	-0.75	5	5
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.1	0.22	-10000	0	-0.78	35	35
ATF2	0	0.31	-10000	0	-0.93	33	33

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.14	0.14	-9999	-0.66	4	4
NF kappa B1 p50/RelA/I kappa B alpha	-0.12	0.11	-9999	-0.58	4	4
alphaV/beta3 Integrin/Osteopontin/Src	-0.21	0.2	-9999	-0.4	255	255
AP1	-0.16	0.16	-9999	-0.61	33	33
ILK	-0.14	0.17	-9999	-0.7	4	4
bone resorption	-0.12	0.12	-9999	-0.59	5	5
PTK2B	0	0	-9999	-10000	0	0
PYK2/p130Cas	-0.14	0.14	-9999	-0.65	4	4
ITGAV	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.001	0.025	-9999	-0.56	1	1
alphaV/beta3 Integrin/Osteopontin	-0.18	0.18	-9999	-0.58	11	11
MAP3K1	-0.14	0.18	-9999	-0.53	11	11
JUN	0	0	-9999	-10000	0	0
MAPK3	-0.12	0.17	-9999	-0.66	4	4
MAPK1	-0.12	0.17	-9999	-0.66	4	4
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
MAPK8	-0.12	0.17	-9999	-0.6	6	6
ITGB3	-0.016	0.11	-9999	-0.73	11	11
NFKBIA	-0.1	0.16	-9999	-0.64	4	4
FOS	-0.09	0.24	-9999	-0.74	61	61
CD44	-0.001	0.033	-9999	-0.74	1	1
CHUK	0	0	-9999	-10000	0	0
PLAU	-0.099	0.17	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.12	0.12	-9999	-0.56	4	4
BCAR1	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.012	0.081	-9999	-0.55	11	11
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.14	0.18	-9999	-0.52	12	12
VAV3	-0.12	0.17	-9999	-0.76	4	4
MAP3K14	-0.14	0.18	-9999	-0.62	6	6
ROCK2	0	0	-9999	-10000	0	0
SPP1	-0.29	0.28	-9999	-0.57	255	255
RAC1	0	0	-9999	-10000	0	0
Rac1/GTP	-0.13	0.13	-9999	-0.7	4	4
MMP2	-0.1	0.17	-9999	-0.64	9	9

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.024	0.11	-10000	0	-0.45	27	27
ER alpha/Gai/GDP/Gbeta gamma	-0.027	0.11	-10000	0	-0.46	25	25
AKT1	-0.007	0.18	-10000	0	-0.82	24	24
PIK3CA	0	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.011	0.18	-10000	0	-0.83	24	24
mol:Ca2+	-0.093	0.23	-10000	0	-0.48	124	124
IGF1R	0	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	-0.023	0.1	-10000	0	-0.48	24	24
SHC1	0	0	-10000	0	-10000	0	0
apoptosis	0.005	0.17	0.78	24	-10000	0	24
RhoA/GTP	-0.017	0.076	-10000	0	-0.36	24	24
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.029	0.12	-10000	0	-0.52	25	25
regulation of stress fiber formation	-0.031	0.076	0.57	2	-10000	0	2
E2/ERA-ERB (dimer)	-0.023	0.1	-10000	0	-0.48	24	24
KRAS	0	0	-10000	0	-10000	0	0
G13/GTP	-0.021	0.095	-10000	0	-0.44	24	24
pseudopodium formation	0.031	0.076	-10000	0	-0.57	2	2
E2/ER alpha (dimer)/PELP1	-0.023	0.1	-10000	0	-0.48	24	24
GRB2	0	0	-10000	0	-10000	0	0
GNG2	-0.007	0.073	-10000	0	-0.74	5	5
GNAO1	-0.004	0.049	-10000	0	-0.63	3	3
HRAS	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.014	0.13	-10000	0	-0.54	25	25
E2/ER beta (dimer)	0	0	-10000	0	-10000	0	0
mol:GDP	-0.024	0.11	-10000	0	-0.5	24	24
mol:NADP	0.014	0.13	-10000	0	-0.54	25	25
PIK3R1	0	0	-10000	0	-10000	0	0
mol:IP3	-0.098	0.24	-10000	0	-0.5	124	124
IGF-1R heterotetramer	0	0	-10000	0	-10000	0	0
PLCB1	-0.13	0.23	-10000	0	-0.51	124	124
PLCB2	-0.13	0.23	-10000	0	-0.52	128	128
IGF1	-0.028	0.14	-10000	0	-0.73	19	19
mol:L-citrulline	0.014	0.13	-10000	0	-0.54	25	25
RHOA	0	0	-10000	0	-10000	0	0
Gai/GDP	-0.007	0.045	-10000	0	-0.67	1	1
JNK cascade	0	0	-10000	0	-10000	0	0
BCAR1	0	0	-10000	0	-10000	0	0
ESR2	0	0	-10000	0	-10000	0	0
GNAQ	-0.001	0.033	-10000	0	-0.74	1	1
ESR1	-0.035	0.16	-10000	0	-0.74	24	24
Gq family/GDP/Gbeta gamma	-0.075	0.14	-10000	0	-0.81	6	6
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.018	0.074	-10000	0	-0.36	1	1
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.029	0.12	-10000	0	-0.52	25	25
GNAZ	-0.009	0.08	-10000	0	-0.74	6	6
E2/ER alpha (dimer)	-0.027	0.12	-10000	0	-0.56	24	24
STRN	0	0	-10000	0	-10000	0	0
GNAL	-0.004	0.057	-10000	0	-0.74	3	3
PELP1	0	0	-10000	0	-10000	0	0
MAPK11	0.016	0	-10000	0	-10000	0	0
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.001	0.033	-10000	0	-0.74	1	1
HBEGF	0.013	0.12	-10000	0	-0.68	6	6
cAMP biosynthetic process	-0.021	0.091	-10000	0	-0.4	26	26
SRC	0.018	0.11	-10000	0	-0.43	25	25
PI3K	0	0	-10000	0	-10000	0	0
GNB1	-0.001	0.033	-10000	0	-0.74	1	1
G13/GDP/Gbeta gamma	-0.025	0.11	-10000	0	-0.48	24	24
SOS1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.032	0.11	-10000	0	-0.46	26	26
Gs family/GTP	-0.021	0.093	-10000	0	-0.41	26	26
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0	0	-10000	0	-10000	0	0
vasodilation	0.015	0.13	-10000	0	-0.52	25	25
mol:DAG	-0.098	0.24	-10000	0	-0.5	124	124
Gs family/GDP/Gbeta gamma	-0.025	0.1	-10000	0	-0.45	24	24
MSN	0.031	0.082	-10000	0	-0.64	2	2
Gq family/GTP	-0.14	0.24	-10000	0	-0.54	123	123
mol:PI-3-4-5-P3	-0.009	0.18	-10000	0	-0.79	24	24
NRAS	0	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.015	0.13	0.52	25	-10000	0	25
GRB2/SOS1	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.022	0.1	-10000	0	-0.47	24	24
NOS3	0.013	0.14	-10000	0	-0.57	25	25
GNA11	0	0	-10000	0	-10000	0	0
MAPKKK cascade	0.018	0.15	-10000	0	-0.63	24	24
E2/ER alpha (dimer)/PELP1/Src	-0.03	0.12	-10000	0	-0.54	25	25
ruffle organization	0.031	0.076	-10000	0	-0.57	2	2
ROCK2	-0.016	0.07	-10000	0	-10000	0	0
GNA14	-0.18	0.32	-10000	0	-0.74	123	123
GNA15	0	0	-10000	0	-10000	0	0
GNA13	0	0	-10000	0	-10000	0	0
MMP9	0.008	0.12	-10000	0	-0.59	5	5
MMP2	0.022	0.12	-10000	0	-0.79	5	5

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0	0	-9999	-10000	0	0
GNAT1/GTP	-0.007	0.053	-9999	-0.42	8	8
Metarhodopsin II/Arrestin	-0.001	0.023	-9999	-0.36	2	2
PDE6G/GNAT1/GTP	-0.015	0.081	-9999	-0.43	18	18
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	-0.009	0.072	-9999	-0.57	8	8
GRK1	-0.002	0.036	-9999	-0.57	2	2
CNG Channel	-0.054	0.13	-9999	-0.6	7	7
mol:Na +	-0.096	0.15	-9999	-0.53	23	23
mol:ADP	-0.002	0.036	-9999	-0.57	2	2
RGS9-1/Gbeta5/R9AP	-0.059	0.16	-9999	-0.49	60	60
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.098	0.15	-9999	-0.54	23	23
CNGB1	-0.051	0.16	-9999	-0.57	44	44
RDH5	-0.003	0.046	-9999	-0.74	2	2
SAG	0	0	-9999	-10000	0	0
mol:Ca2+	-0.091	0.14	-9999	-0.51	23	23
Na + (4 Units)	-0.089	0.14	-9999	-0.49	23	23
RGS9	-0.078	0.23	-9999	-0.74	53	53
GNB1/GNGT1	-0.13	0.19	-9999	-0.42	157	157
GNAT1/GDP	-0.055	0.14	-9999	-0.43	60	60
GUCY2D	0	0	-9999	-10000	0	0
GNGT1	-0.18	0.27	-9999	-0.57	156	156
GUCY2F	0	0	-9999	-10000	0	0
GNB5	0	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.031	0.11	-9999	-0.43	30	30
mol:11-cis-retinal	-0.003	0.046	-9999	-0.74	2	2
mol:cGMP	-0.081	0.13	-9999	-10000	0	0
GNB1	-0.001	0.033	-9999	-0.74	1	1
Rhodopsin	-0.004	0.044	-9999	-0.49	4	4
SLC24A1	0	0	-9999	-10000	0	0
CNGA1	-0.007	0.063	-9999	-0.57	6	6
Metarhodopsin II	-0.003	0.029	-9999	-0.32	4	4
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.086	0.14	-9999	-10000	0	0
RGS9BP	-0.013	0.098	-9999	-0.74	9	9
Metarhodopsin II/Transducin	-0.052	0.077	-9999	-0.34	3	3
GCAP Family/Ca ++	-0.088	0.14	-9999	-10000	0	0
PDE6A/B	-0.025	0.11	-9999	-0.54	23	23
mol:Pi	-0.058	0.16	-9999	-0.49	60	60
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.1	0.15	-9999	-0.56	3	3
PDE6B	-0.016	0.11	-9999	-0.72	11	11
PDE6A	-0.017	0.11	-9999	-0.71	12	12
PDE6G	-0.015	0.1	-9999	-0.74	10	10
RHO	-0.002	0.036	-9999	-0.57	2	2
PDE6	-0.071	0.17	-9999	-0.8	11	11
GUCA1A	-0.16	0.26	-9999	-0.57	137	137
GC2/GCAP Family	-0.088	0.14	-9999	-10000	0	0
GUCA1C	0	0	-9999	-10000	0	0
GUCA1B	0	0	-9999	-10000	0	0

×

HIF-2-alpha transcription factor network

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
MMP14	-0.013	0.03	-10000	0	-10000	0	0
oxygen homeostasis	-0.01	0.013	-10000	0	-10000	0	0
TCEB2	0	0	-10000	0	-10000	0	0
TCEB1	0	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.1	0.12	-10000	0	-0.43	18	18
EPO	-0.15	0.22	-10000	0	-0.69	14	14
FIH (dimer)	0.003	0.009	-10000	0	-10000	0	0
APEX1	0.004	0.013	-10000	0	-10000	0	0
SERPINE1	-0.2	0.25	-10000	0	-0.8	17	17
FLT1	-0.038	0.16	-10000	0	-1	12	12
ADORA2A	-0.19	0.24	-10000	0	-0.78	16	16
germ cell development	-0.2	0.24	-10000	0	-0.77	21	21
SLC11A2	-0.2	0.25	-10000	0	-0.8	17	17
BHLHE40	-0.2	0.25	-10000	0	-0.8	17	17
HIF1AN	0.003	0.009	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.14	0.16	-10000	0	-0.5	36	36
ETS1	0.004	0.12	-10000	0	-0.75	12	12
CITED2	-0.037	0.18	-10000	0	-1.3	10	10
KDR	-0.096	0.34	-10000	0	-1.3	34	34
PGK1	-0.2	0.25	-10000	0	-0.8	17	17
SIRT1	0	0	-10000	0	-10000	0	0
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	-0.21	0.3	-10000	0	-0.83	40	40
EPAS1	-0.12	0.16	-10000	0	-0.41	76	76
SP1	0.017	0	-10000	0	-10000	0	0
ABCG2	-0.25	0.34	-10000	0	-0.96	63	63
EFNA1	-0.2	0.25	-10000	0	-0.8	17	17
FXN	-0.19	0.24	-10000	0	-0.78	16	16
POU5F1	-0.2	0.25	-10000	0	-0.81	21	21
neuron apoptosis	0.21	0.29	0.8	40	-10000	0	40
EP300	0	0	-10000	0	-10000	0	0
EGLN3	-0.087	0.21	-10000	0	-0.59	76	76
EGLN2	0.003	0.01	-10000	0	-10000	0	0
EGLN1	0.003	0.009	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0	0	-10000	0	-10000	0	0
VHL	0	0	-10000	0	-10000	0	0
ARNT	0.004	0.013	-10000	0	-10000	0	0
SLC2A1	-0.38	0.29	-10000	0	-0.8	74	74
TWIST1	-0.27	0.31	-10000	0	-0.8	55	55
ELK1	0.016	0.002	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.14	0.16	-10000	0	-0.54	17	17
VEGFA	-0.2	0.25	-10000	0	-0.8	17	17
CREBBP	0	0	-10000	0	-10000	0	0

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.041	0.14	-10000	0	-0.6	25	25
FYN	0.001	0.23	-10000	0	-0.86	27	27
LAT/GRAP2/SLP76	-0.056	0.18	-10000	0	-0.67	34	34
IKBKB	-0.001	0.026	-10000	0	-0.57	1	1
AKT1	0.022	0.14	-10000	0	-0.47	32	32
B2M	0.006	0.058	-10000	0	-0.74	3	3
IKBKG	-0.01	0.031	-10000	0	-0.18	1	1
MAP3K8	-0.003	0.046	-10000	0	-0.74	2	2
mol:Ca2+	-0.006	0.021	-10000	0	-0.13	7	7
integrin-mediated signaling pathway	-0.001	0.021	-10000	0	-0.48	1	1
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.008	0.21	-10000	0	-0.73	32	32
TRPV6	-0.017	0.11	-10000	0	-0.7	13	13
CD28	0.002	0.075	-10000	0	-0.74	5	5
SHC1	0.005	0.21	-10000	0	-0.78	27	27
receptor internalization	-0.011	0.23	-10000	0	-0.81	32	32
PRF1	-0.037	0.32	-10000	0	-1.2	31	31
KRAS	0	0	-10000	0	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
COT/AKT1	0.026	0.11	-10000	0	-0.4	25	25
LAT	0.005	0.21	-10000	0	-0.77	28	28
EntrezGene:6955	0.001	0.004	-10000	0	-10000	0	0
CD3D	-0.006	0.11	-10000	0	-0.75	11	11
CD3E	-0.003	0.1	-10000	0	-0.75	9	9
CD3G	-0.037	0.18	-10000	0	-0.74	32	32
RASGRP2	-0.013	0.066	-10000	0	-0.18	68	68
RASGRP1	0.022	0.15	-10000	0	-0.49	28	28
HLA-A	0.009	0.034	-10000	0	-0.75	1	1
RASSF5	-0.001	0.033	-10000	0	-0.74	1	1
RAP1A/GTP/RAPL	-0.001	0.022	-10000	0	-0.48	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.022	0.05	-10000	0	-0.13	25	25
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.018	0.055	-10000	0	-0.25	14	14
PRKCA	-0.024	0.077	-10000	0	-0.31	25	25
GRAP2	-0.044	0.18	-10000	0	-0.74	30	30
mol:IP3	-0.036	0.13	0.25	9	-0.49	29	38
EntrezGene:6957	0.001	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.017	0.23	-10000	0	-0.83	28	28
ORAI1	0.009	0.061	0.35	13	-0.57	1	14
CSK	0.003	0.21	-10000	0	-0.8	27	27
B7 family/CD28	-0.064	0.22	-10000	0	-0.91	28	28
CHUK	0	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.01	0.25	-10000	0	-0.94	28	28
PTPN6	0	0.21	-10000	0	-0.82	26	26
VAV1	0.002	0.21	-10000	0	-0.8	28	28
Monovalent TCR/CD3	-0.025	0.21	-10000	0	-0.62	39	39
CBL	0	0	-10000	0	-10000	0	0
LCK	-0.002	0.23	-10000	0	-0.88	27	27
PAG1	0	0.22	-10000	0	-0.81	27	27
RAP1A	0	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.011	0.25	-10000	0	-0.94	28	28
CD80	-0.016	0.14	-10000	0	-0.74	17	17
CD86	0.002	0.075	-10000	0	-0.74	5	5
PDK1/CARD11/BCL10/MALT1	-0.021	0.066	-10000	0	-0.3	15	15
HRAS	0	0	-10000	0	-10000	0	0
GO:0035030	0.005	0.19	-10000	0	-0.7	28	28
CD8A	0	0.089	-10000	0	-0.75	7	7
CD8B	-0.013	0.13	-10000	0	-0.7	17	17
PTPRC	-0.04	0.19	-10000	0	-0.74	33	33
PDK1/PKC theta	0.016	0.18	-10000	0	-0.59	34	34
CSK/PAG1	0.006	0.2	-10000	0	-0.83	23	23
SOS1	0	0	-10000	0	-10000	0	0
peptide-MHC class I	-0.004	0.058	-10000	0	-0.72	3	3
GRAP2/SLP76	-0.066	0.21	-10000	0	-0.78	35	35
STIM1	0.006	0.03	-10000	0	-10000	0	0
RAS family/GTP	0.035	0.059	-10000	0	-0.18	19	19
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.016	0.26	-10000	0	-0.91	32	32
mol:DAG	-0.034	0.11	-10000	0	-0.43	29	29
RAP1A/GDP	0.01	0.022	-10000	0	-10000	0	0
PLCG1	0.001	0.003	-10000	0	-10000	0	0
CD247	-0.008	0.12	-10000	0	-0.75	12	12
cytotoxic T cell degranulation	-0.03	0.29	-10000	0	-1.1	32	32
RAP1A/GTP	-0.009	0.022	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.016	0.17	-10000	0	-0.57	32	32
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.047	0.17	0.27	9	-0.65	29	38
NRAS	0	0	-10000	0	-10000	0	0
ZAP70	-0.011	0.093	-10000	0	-0.74	8	8
GRB2/SOS1	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.052	0.16	-10000	0	-0.64	32	32
MALT1	0	0	-10000	0	-10000	0	0
TRAF6	0	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.025	0.13	-10000	0	-0.65	19	19
CARD11	-0.004	0.049	-10000	0	-0.63	3	3
PRKCB	-0.035	0.1	-10000	0	-0.37	36	36
PRKCE	-0.024	0.075	-10000	0	-0.3	25	25
PRKCQ	0.004	0.21	-10000	0	-0.68	35	35
LCP2	-0.008	0.08	-10000	0	-0.74	6	6
BCL10	0	0	-10000	0	-10000	0	0
regulation of survival gene product expression	0.025	0.12	-10000	0	-0.39	32	32
IKK complex	0.035	0.047	-10000	0	-0.13	10	10
RAS family/GDP	-0.003	0.008	-10000	0	-10000	0	0
MAP3K14	0.031	0.089	-10000	0	-0.31	20	20
PDPK1	0.025	0.13	-10000	0	-0.47	27	27
TCR/CD3/MHC I/CD8/Fyn	-0.013	0.25	-10000	0	-0.96	26	26

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0	0	-9999	-10000	0	0
VLDLR	-0.003	0.046	-9999	-0.74	2	2
LRPAP1	0	0	-9999	-10000	0	0
NUDC	0	0	-9999	-10000	0	0
RELN/LRP8	-0.086	0.18	-9999	-0.48	86	86
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.053	0.18	-9999	-0.43	86	86
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	-0.033	0.13	-9999	-0.57	29	29
IQGAP1	0	0	-9999	-10000	0	0
PLA2G7	-0.006	0.066	-9999	-0.74	4	4
CALM1	0	0	-9999	-10000	0	0
DYNLT1	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.002	0.032	-9999	-0.42	3	3
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0	0	-9999	-10000	0	0
CDK5R1	-0.011	0.08	-9999	-0.57	10	10
LIS1/Poliovirus Protein 3A	0	0	-9999	-10000	0	0
CDK5R2	-0.15	0.25	-9999	-0.57	131	131
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.11	0.2	-9999	-0.46	115	115
YWHAE	0	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.093	0.14	-9999	-0.48	29	29
MAP1B	-0.002	0.019	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.072	0.15	-9999	-0.62	3	3
RELN	-0.13	0.28	-9999	-0.73	89	89
PAFAH/LIS1	-0.004	0.042	-9999	-0.48	4	4
LIS1/CLIP170	0	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.069	0.11	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.062	0.12	-9999	-0.51	5	5
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.1	0.15	-9999	-0.51	29	29
LIS1/IQGAP1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.02	0	-9999	-10000	0	0
PAFAH1B3	-0.006	0.061	-9999	-0.61	5	5
PAFAH1B2	0	0	-9999	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	-0.001	0.012	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.087	0.14	-9999	-0.46	29	29
LRP8	-0.003	0.044	-9999	-0.57	3	3
NDEL1/Katanin 60	-0.093	0.14	-9999	-0.48	29	29
P39/CDK5	-0.14	0.19	-9999	-0.66	27	27
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0	0	-9999	-10000	0	0
CDK5	-0.042	0.16	-9999	-10000	0	0
PPP2R5D	0	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0	-9999	-10000	0	0
CSNK2A1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.089	0.17	-9999	-0.42	89	89
RELN/VLDLR	-0.079	0.17	-9999	-0.44	87	87
CDC42	0	0	-9999	-10000	0	0

×

PDGFR-alpha signaling pathway

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
PDGFRA	-0.003	0.087	-9999	-0.73	7	7
PDGF/PDGFRA/CRKL	-0.008	0.063	-9999	-0.53	7	7
positive regulation of JUN kinase activity	-0.006	0.047	-9999	-0.42	6	6
CRKL	0	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.095	0.21	-9999	-0.56	83	83
AP1	-0.14	0.36	-9999	-1.1	61	61
mol:IP3	0.008	0.07	-9999	-0.55	7	7
PLCG1	0.008	0.07	-9999	-0.55	7	7
PDGF/PDGFRA/alphaV Integrin	-0.008	0.063	-9999	-0.53	7	7
RAPGEF1	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
mol:Ca2+	0.008	0.07	-9999	-0.55	7	7
CAV3	-0.11	0.26	-9999	-0.74	76	76
CAV1	-0.2	0.33	-9999	-0.74	137	137
SHC/Grb2/SOS1	-0.006	0.048	-9999	-0.42	6	6
PDGF/PDGFRA/Shf	-0.008	0.063	-9999	-0.53	7	7
FOS	-0.096	0.36	-9999	-1.1	61	61
JUN	-0.008	0.02	-9999	-10000	0	0
oligodendrocyte development	-0.008	0.063	-9999	-0.53	7	7
GRB2	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
mol:DAG	0.008	0.07	-9999	-0.55	7	7
PDGF/PDGFRA	-0.003	0.087	-9999	-0.72	7	7
actin cytoskeleton reorganization	-0.008	0.063	-9999	-0.53	7	7
SRF	0.021	0.009	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
PI3K	-0.006	0.053	-9999	-0.47	6	6
PDGF/PDGFRA/Crk/C3G	-0.006	0.053	-9999	-0.47	6	6
JAK1	0.011	0.065	-9999	-0.53	7	7
ELK1/SRF	-0.007	0.048	-9999	-0.48	2	2
SHB	0	0	-9999	-10000	0	0
SHF	0	0	-9999	-10000	0	0
CSNK2A1	0.007	0.019	-9999	-10000	0	0
GO:0007205	0.008	0.072	-9999	-0.56	7	7
SOS1	0	0	-9999	-10000	0	0
Ras protein signal transduction	-0.006	0.047	-9999	-0.42	6	6
PDGF/PDGFRA/SHB	-0.008	0.063	-9999	-0.53	7	7
PDGF/PDGFRA/Caveolin-1	-0.16	0.26	-9999	-0.58	141	141
ITGAV	0	0	-9999	-10000	0	0
ELK1	0.011	0.071	-9999	-0.53	6	6
PIK3CA	0	0	-9999	-10000	0	0
PDGF/PDGFRA/Crk	-0.008	0.063	-9999	-0.53	7	7
JAK-STAT cascade	0.011	0.065	-9999	-0.53	7	7
cell proliferation	-0.008	0.063	-9999	-0.53	7	7

×

Ephrin A reverse signaling

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
MAPKKK cascade	-0.018	0.079	-9999	-0.37	24	24
EFNA5	-0.004	0.057	-9999	-0.74	3	3
FYN	0.002	0.078	-9999	-0.44	4	4
neuron projection morphogenesis	-0.018	0.079	-9999	-0.37	24	24
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.018	0.08	-9999	-0.37	24	24
EPHA5	-0.024	0.12	-9999	-0.57	21	21

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.003	0.04	-10000	0	-0.51	3	3
CRKL	-0.027	0.12	-10000	0	-0.43	2	2
mol:PIP3	-0.014	0.043	0.66	2	-10000	0	2
AKT1	0.004	0.028	0.43	2	-10000	0	2
PTK2B	0	0	-10000	0	-10000	0	0
RAPGEF1	-0.018	0.11	-10000	0	-0.4	2	2
RANBP10	0	0	-10000	0	-10000	0	0
PIK3CA	0	0	-10000	0	-10000	0	0
HGF/MET/SHIP2	-0.1	0.2	-10000	0	-0.48	110	110
MAP3K5	-0.011	0.11	-10000	0	-0.44	4	4
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.097	0.18	-10000	0	-0.44	110	110
AP1	-0.061	0.16	-10000	0	-0.5	61	61
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
apoptosis	-0.079	0.24	-10000	0	-0.73	61	61
STAT3 (dimer)	-0.035	0.14	-10000	0	-10000	0	0
GAB1/CRKL/SHP2/PI3K	-0.045	0.086	-10000	0	-10000	0	0
INPP5D	-0.001	0.033	-10000	0	-0.74	1	1
CBL/CRK	-0.02	0.11	-10000	0	-0.4	2	2
PTPN11	0	0	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0	0	-10000	0	-10000	0	0
PTEN	-0.003	0.046	-10000	0	-0.74	2	2
ELK1	-0.004	0.022	-10000	0	-0.24	3	3
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.04	0.076	-10000	0	-0.46	2	2
PAK1	0.01	0.029	0.4	2	-10000	0	2
HGF/MET/RANBP10	-0.1	0.2	-10000	0	-0.48	110	110
HRAS	-0.081	0.16	-10000	0	-0.59	4	4
DOCK1	-0.018	0.11	-10000	0	-0.4	2	2
GAB1	-0.035	0.12	-10000	0	-0.39	4	4
CRK	-0.027	0.12	-10000	0	-0.43	2	2
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.12	0.22	-10000	0	-0.54	110	110
JUN	0	0	-10000	0	-10000	0	0
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.055	0.1	-10000	0	-0.25	110	110
PIK3R1	0	0	-10000	0	-10000	0	0
cell morphogenesis	-0.012	0.14	-10000	0	-10000	0	0
GRB2/SHC	-0.046	0.088	-10000	0	-0.5	2	2
FOS	-0.09	0.24	-10000	0	-0.74	61	61
GLMN	0	0	-10000	0	-10000	0	0
cell motility	-0.004	0.022	-10000	0	-0.24	3	3
HGF/MET/MUC20	-0.11	0.2	-10000	0	-0.48	111	111
cell migration	-0.045	0.087	-10000	0	-0.49	2	2
GRB2	0	0	-10000	0	-10000	0	0
CBL	0	0	-10000	0	-10000	0	0
MET/RANBP10	-0.003	0.04	-10000	0	-0.51	3	3
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.067	0.13	-10000	0	-10000	0	0
MET/MUC20	-0.003	0.04	-10000	0	-0.52	3	3
RAP1B	-0.01	0.11	-10000	0	-10000	0	0
RAP1A	-0.01	0.11	-10000	0	-10000	0	0
HGF/MET/RANBP9	-0.1	0.2	-10000	0	-0.48	110	110
RAF1	-0.045	0.16	-10000	0	-0.55	4	4
STAT3	-0.064	0.12	-10000	0	-10000	0	0
cell proliferation	-0.049	0.19	-10000	0	-0.52	4	4
RPS6KB1	-0.019	0.036	-10000	0	-10000	0	0
MAPK3	-0.007	0.019	-10000	0	-0.23	2	2
MAPK1	-0.007	0.019	-10000	0	-0.23	2	2
RANBP9	0	0	-10000	0	-10000	0	0
MAPK8	0.008	0.095	-10000	0	-0.39	1	1
SRC	-0.032	0.13	-10000	0	-10000	0	0
PI3K	-0.046	0.088	-10000	0	-0.5	2	2
MET/Glomulin	-0.003	0.036	-10000	0	-0.46	3	3
SOS1	0	0	-10000	0	-10000	0	0
MAP2K1	-0.035	0.15	-10000	0	-0.59	2	2
MET	-0.004	0.053	-10000	0	-0.68	3	3
MAP4K1	-0.019	0.12	-10000	0	-0.47	4	4
PTK2	0	0	-10000	0	-10000	0	0
MAP2K2	-0.035	0.15	-10000	0	-0.59	2	2
BAD	0.011	0.025	0.4	2	-10000	0	2
MAP2K4	-0.003	0.1	-10000	0	-0.39	4	4
SHP2/GRB2/SOS1/GAB1	-0.048	0.091	-10000	0	-0.44	2	2
INPPL1	0	0	-10000	0	-10000	0	0
PXN	0	0	-10000	0	-10000	0	0
SH3KBP1	-0.003	0.046	-10000	0	-0.74	2	2
HGS	-0.049	0.095	-10000	0	-0.42	4	4
PLCgamma1/PKC	0	0	-10000	0	-10000	0	0
HGF	-0.16	0.3	-10000	0	-0.74	108	108
RASA1	0	0	-10000	0	-10000	0	0
NCK1	0	0	-10000	0	-10000	0	0
PTPRJ	-0.003	0.046	-10000	0	-0.74	2	2
NCK/PLCgamma1	-0.052	0.099	-10000	0	-0.52	2	2
PDPK1	-0.004	0.032	0.5	2	-10000	0	2
HGF/MET/SHIP	-0.11	0.2	-10000	0	-0.48	110	110

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0	0	-9999	-10000	0	0
EGFR	-0.023	0.12	-9999	-0.63	18	18
EGF/EGFR	-0.058	0.15	-9999	-0.45	56	56
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.019	0.083	-9999	-0.44	12	12
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.009	0.08	-9999	-0.74	6	6
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.014	0.097	-9999	-0.69	10	10
EGF/EGFR dimer/SHC	-0.023	0.098	-9999	-0.42	27	27
mol:GDP	-0.019	0.082	-9999	-0.43	12	12
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.065	0.21	-9999	-0.74	44	44
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.017	0.075	-9999	-0.74	1	1
SHC1	0	0	-9999	-10000	0	0
HRAS/GDP	-0.017	0.076	-9999	-0.75	1	1
FRAP1	-0.018	0.079	-9999	-0.41	12	12
EGF/EGFR dimer	-0.027	0.12	-9999	-0.49	27	27
SOS1	0	0	-9999	-10000	0	0
GRB2	0	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.055	0.17	-9999	-0.56	50	50

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.1	0.26	-9999	-0.74	70	70
GNB1/GNG2	-0.042	0.091	-9999	-0.58	5	5
mol:DAG	-0.003	0.099	-9999	-0.53	5	5
PLCG1	-0.003	0.1	-9999	-0.55	5	5
YES1	-0.012	0.098	-9999	-0.64	2	2
FZD3	0	0	-9999	-10000	0	0
FZD6	0	0	-9999	-10000	0	0
G protein	-0.039	0.086	-9999	-0.59	4	4
MAP3K7	-0.016	0.14	-9999	-0.54	14	14
mol:Ca2+	-0.002	0.097	-9999	-0.51	5	5
mol:IP3	-0.003	0.099	-9999	-0.53	5	5
NLK	-0.003	0.007	-9999	-10000	0	0
GNB1	-0.001	0.033	-9999	-0.74	1	1
CAMK2A	-0.025	0.15	-9999	-0.58	15	15
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.045	0.091	-9999	-0.34	25	25
CSNK1A1	0	0	-9999	-10000	0	0
GNAS	-0.012	0.098	-9999	-0.64	2	2
GO:0007205	-0.002	0.098	-9999	-0.56	4	4
WNT6	-0.094	0.21	-9999	-0.57	82	82
WNT4	-0.01	0.083	-9999	-0.66	8	8
NFAT1/CK1 alpha	-0.081	0.15	-9999	-0.56	18	18
GNG2	-0.007	0.073	-9999	-0.74	5	5
WNT5A	-0.014	0.093	-9999	-0.6	12	12
WNT11	-0.038	0.16	-9999	-0.68	28	28
CDC42	-0.004	0.094	-9999	-0.6	2	2

×

Caspase cascade in apoptosis

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
TOP1	0.001	0.12	-10000	0	-0.48	25	25
ACTA1	-0.011	0.16	-10000	0	-0.64	25	25
NUMA1	0.001	0.12	-10000	0	-0.48	25	25
SPTAN1	-0.009	0.15	-10000	0	-0.64	25	25
LIMK1	-0.009	0.15	-10000	0	-0.64	25	25
BIRC3	-0.009	0.08	-10000	0	-0.74	6	6
BIRC2	0	0.002	-10000	0	-10000	0	0
BAX	0	0	-10000	0	-10000	0	0
CASP10	-0.01	0.16	-10000	0	-0.63	28	28
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	0.001	0.12	-10000	0	-0.48	25	25
DIABLO	0	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.009	0.15	-10000	0	-0.62	25	25
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0	0	-10000	0	-10000	0	0
GSN	-0.009	0.16	-10000	0	-0.64	25	25
MADD	0	0	-10000	0	-10000	0	0
TFAP2A	-0.071	0.12	-10000	0	-0.78	12	12
BID	0.005	0.073	-10000	0	-0.3	27	27
MAP3K1	0.004	0.046	-10000	0	-0.23	10	10
TRADD	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.01	0.16	-10000	0	-0.63	26	26
CASP9	0.001	0.002	-10000	0	-10000	0	0
DNA repair	-0.002	0.034	-10000	0	-0.21	2	2
neuron apoptosis	0.019	0.016	-10000	0	-10000	0	0
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.003	0.15	-10000	0	-0.61	25	25
APAF1	0.001	0.003	-10000	0	-10000	0	0
CASP6	0.018	0.072	-10000	0	-0.42	4	4
TRAF2	0	0	-10000	0	-10000	0	0
ICAD/CAD	-0.002	0.15	-10000	0	-0.61	25	25
CASP7	-0.005	0.042	0.36	6	-10000	0	6
KRT18	0.013	0.019	-10000	0	-10000	0	0
apoptosis	-0.001	0.14	-10000	0	-0.56	25	25
DFFA	-0.009	0.15	-10000	0	-0.64	25	25
DFFB	-0.009	0.15	-10000	0	-0.64	25	25
PARP1	0.002	0.034	0.21	2	-10000	0	2
actin filament polymerization	0.001	0.14	0.58	25	-10000	0	25
TNF	-0.019	0.12	-10000	0	-0.72	13	13
CYCS	0.008	0.055	-10000	0	-0.26	12	12
SATB1	0.021	0.078	-10000	0	-0.5	4	4
SLK	-0.009	0.15	-10000	0	-0.64	25	25
p15 BID/BAX	-0.014	0.061	-10000	0	-0.34	10	10
CASP2	0.035	0.051	-10000	0	-0.44	1	1
JNK cascade	-0.004	0.046	0.23	10	-10000	0	10
CASP3	-0.017	0.16	-10000	0	-0.68	25	25
LMNB2	0.033	0.048	-10000	0	-0.48	1	1
RIPK1	0	0	-10000	0	-10000	0	0
CASP4	-0.001	0.033	-10000	0	-0.74	1	1
Mammalian IAPs/DIABLO	-0.005	0.047	-10000	0	-0.43	6	6
negative regulation of DNA binding	-0.07	0.12	-10000	0	-0.77	12	12
stress fiber formation	-0.009	0.15	-10000	0	-0.62	25	25
GZMB	-0.02	0.18	-10000	0	-0.72	27	27
CASP1	0.012	0.051	-10000	0	-0.72	2	2
LMNB1	0.033	0.048	-10000	0	-0.48	1	1
APP	0.019	0.016	-10000	0	-10000	0	0
TNFRSF1A	0	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.01	0	-10000	0	-10000	0	0
VIM	-0.007	0.14	-10000	0	-0.55	25	25
LMNA	0.033	0.048	-10000	0	-0.48	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.009	0.046	-10000	0	-0.46	1	1
LRDD	-0.001	0.033	-10000	0	-0.74	1	1
SREBF1	-0.009	0.15	-10000	0	-0.64	25	25
APAF-1/Caspase 9	-0.002	0.022	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0.001	0.12	-10000	0	-0.47	25	25
CFL2	-0.002	0.15	-10000	0	-0.6	25	25
GAS2	-0.061	0.21	-10000	0	-0.52	72	72
positive regulation of apoptosis	0.035	0.048	-10000	0	-0.47	1	1
PRF1	-0.037	0.16	-10000	0	-0.74	25	25

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.007	0.013	-10000	0	-10000	0	0
HSPA8	0	0.001	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.027	0.11	-10000	0	-0.52	24	24
AKT1	0.006	0.022	-10000	0	-10000	0	0
GSC	-0.037	0.14	-10000	0	-0.48	2	2
NKX2-5	-0.3	0.29	-10000	0	-0.57	258	258
muscle cell differentiation	0.094	0.1	0.45	6	-10000	0	6
SMAD2-3/SMAD4/SP1	-0.009	0.037	-10000	0	-10000	0	0
SMAD4	0.016	0.027	-10000	0	-10000	0	0
CBFB	0	0	-10000	0	-10000	0	0
SAP18	0	0.001	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.01	0.035	-10000	0	-0.46	1	1
SMAD3/SMAD4/VDR	0.009	0.032	-10000	0	-10000	0	0
MYC	0.008	0.025	-10000	0	-10000	0	0
CDKN2B	-0.1	0.43	-10000	0	-1.5	46	46
AP1	-0.038	0.12	-10000	0	-0.41	2	2
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0	0.006	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.031	0.09	-10000	0	-0.42	4	4
SP3	0	0	-10000	0	-10000	0	0
CREB1	0	0	-10000	0	-10000	0	0
FOXH1	-0.044	0.16	-10000	0	-0.58	42	42
SMAD3/SMAD4/GR	-0.003	0.015	-10000	0	-10000	0	0
GATA3	-0.025	0.13	-10000	0	-0.71	17	17
SKI/SIN3/HDAC complex/NCoR1	0	0.003	-10000	0	-10000	0	0
MEF2C/TIF2	-0.17	0.2	-10000	0	-0.71	33	33
endothelial cell migration	-0.011	0.068	1.4	1	-10000	0	1
MAX	0	0.003	-10000	0	-10000	0	0
RBBP7	0	0.001	-10000	0	-10000	0	0
RBBP4	0	0.001	-10000	0	-10000	0	0
RUNX2	0	0	-10000	0	-10000	0	0
RUNX3	0	0	-10000	0	-10000	0	0
RUNX1	0	0	-10000	0	-10000	0	0
CTBP1	0	0	-10000	0	-10000	0	0
NR3C1	0	0.003	-10000	0	-10000	0	0
VDR	-0.001	0.033	-10000	0	-0.74	1	1
CDKN1A	0.058	0.043	-10000	0	-10000	0	0
KAT2B	0.002	0.034	-10000	0	-0.74	1	1
SMAD2/SMAD2/SMAD4/FOXH1	-0.045	0.11	-10000	0	-0.48	12	12
DCP1A	0	0	-10000	0	-10000	0	0
SKI	0	0.001	-10000	0	-10000	0	0
SERPINE1	0.01	0.069	-10000	0	-1.4	1	1
SMAD3/SMAD4/ATF2	-0.001	0.017	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	-0.003	0.039	-10000	0	-0.57	2	2
SAP30	0	0.001	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.016	0.032	-10000	0	-10000	0	0
JUN	0.004	0.14	-10000	0	-10000	0	0
SMAD3/SMAD4/IRF7	-0.004	0.038	-10000	0	-0.54	2	2
TFE3	0.016	0.002	-10000	0	-10000	0	0
COL1A2	0.006	0.052	-10000	0	-10000	0	0
mesenchymal cell differentiation	0.001	0.017	-10000	0	-10000	0	0
DLX1	-0.34	0.28	-10000	0	-0.57	292	292
TCF3	0	0	-10000	0	-10000	0	0
FOS	-0.076	0.24	-10000	0	-0.73	61	61
SMAD3/SMAD4/Max	-0.003	0.015	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0	0.015	-10000	0	-10000	0	0
ZBTB17	0.006	0.019	-10000	0	-10000	0	0
LAMC1	0.047	0.029	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	-0.001	0.017	-10000	0	-10000	0	0
IRF7	-0.003	0.047	-10000	0	-0.74	2	2
ESR1	-0.035	0.16	-10000	0	-0.74	24	24
HNF4A	-0.009	0.072	-10000	0	-0.57	8	8
MEF2C	-0.17	0.23	-10000	0	-0.74	34	34
SMAD2-3/SMAD4	-0.01	0.031	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.011	0.022	-10000	0	-10000	0	0
IGHV3OR16-13	0	0.001	-10000	0	-10000	0	0
TGIF2/HDAC complex	0	0	-10000	0	-10000	0	0
CREBBP	0.006	0.01	-10000	0	-10000	0	0
SKIL	0	0	-10000	0	-10000	0	0
HDAC1	0	0.001	-10000	0	-10000	0	0
HDAC2	0	0.001	-10000	0	-10000	0	0
SNIP1	-0.001	0.026	-10000	0	-0.58	1	1
GCN5L2	0.003	0.008	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.003	0.022	-10000	0	-10000	0	0
MSG1/HSC70	-0.002	0.031	-10000	0	-0.49	2	2
SMAD2	0.003	0.029	-10000	0	-10000	0	0
SMAD3	0.019	0.022	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.038	0.027	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.014	0.023	-10000	0	-0.42	1	1
NCOR1	0	0.001	-10000	0	-10000	0	0
NCOA2	-0.001	0.033	-10000	0	-0.74	1	1
NCOA1	0	0	-10000	0	-10000	0	0
MYOD/E2A	-0.059	0.14	-10000	0	-0.42	71	71
SMAD2-3/SMAD4/SP1/MIZ-1	0.018	0.055	-10000	0	-10000	0	0
IFNB1	0.034	0.048	-10000	0	-0.48	3	3
SMAD3/SMAD4/MEF2C	-0.17	0.2	-10000	0	-0.77	26	26
CITED1	-0.003	0.042	-10000	0	-0.66	2	2
SMAD2-3/SMAD4/ARC105	-0.008	0.025	-10000	0	-10000	0	0
RBL1	0	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.008	0.16	-10000	0	-0.48	46	46
RUNX1-3/PEBPB2	0	0	-10000	0	-10000	0	0
SMAD7	-0.025	0.097	-10000	0	-10000	0	0
MYC/MIZ-1	0.014	0.044	-10000	0	-10000	0	0
SMAD3/SMAD4	0.035	0.076	0.3	8	-0.45	1	9
IL10	0.026	0.11	-10000	0	-0.67	6	6
PIASy/HDAC complex	0.007	0.006	-10000	0	-10000	0	0
PIAS3	0.004	0.007	-10000	0	-10000	0	0
CDK2	0.006	0.01	-10000	0	-10000	0	0
IL5	0.023	0.095	-10000	0	-0.57	2	2
CDK4	0.005	0.028	-10000	0	-0.58	1	1
PIAS4	0.007	0.006	-10000	0	-10000	0	0
ATF3	-0.003	0.046	-10000	0	-0.74	2	2
SMAD3/SMAD4/SP1	0.001	0.027	-10000	0	-10000	0	0
FOXG1	-0.064	0.18	-10000	0	-0.58	55	55
FOXO3	0.015	0.029	-10000	0	-10000	0	0
FOXO1	0.015	0.029	-10000	0	-10000	0	0
FOXO4	0.015	0.029	-10000	0	-10000	0	0
heart looping	-0.16	0.22	-10000	0	-0.72	34	34
CEBPB	0.008	0.011	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.21	0.18	-10000	0	-0.41	63	63
MYOD1	-0.082	0.2	-10000	0	-0.57	71	71
SMAD3/SMAD4/HNF4	-0.007	0.047	-10000	0	-10000	0	0
SMAD3/SMAD4/GATA3	-0.02	0.093	-10000	0	-0.51	15	15
SnoN/SIN3/HDAC complex/NCoR1	0	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.001	0.009	-10000	0	-10000	0	0
SMAD3/SMAD4/SP1-3	0.004	0.025	-10000	0	-10000	0	0
MED15	0	0	-10000	0	-10000	0	0
SP1	0.017	0.011	-10000	0	-10000	0	0
SIN3B	0	0.001	-10000	0	-10000	0	0
SIN3A	0	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.2	0.19	-10000	0	-0.64	35	35
ITGB5	0.055	0.035	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0	0.002	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.1	0.2	-10000	0	-0.5	103	103
AR	-0.15	0.3	-10000	0	-0.74	103	103
negative regulation of cell growth	0.003	0.027	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	-0.053	0.13	-10000	0	-0.41	16	16
E2F5	0	0	-10000	0	-10000	0	0
E2F4	0	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.03	0.086	-10000	0	-0.46	3	3
SMAD2-3/SMAD4/FOXO1-3a-4	-0.02	0.098	-10000	0	-0.36	2	2
TFDP1	-0.003	0.044	-10000	0	-0.57	3	3
SMAD3/SMAD4/AP1	-0.038	0.12	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX2	-0.001	0.017	-10000	0	-10000	0	0
TGIF2	0	0	-10000	0	-10000	0	0
TGIF1	0	0	-10000	0	-10000	0	0
ATF2	0	0	-10000	0	-10000	0	0

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.017	0.093	-9999	-0.5	17	17
EPHB2	-0.009	0.072	-9999	-0.57	8	8
Syndecan-2/TACI	-0.015	0.079	-9999	-0.42	18	18
LAMA1	-0.17	0.26	-9999	-0.58	146	146
Syndecan-2/alpha2 ITGB1	-0.014	0.079	-9999	-0.43	17	17
HRAS	0	0	-9999	-10000	0	0
Syndecan-2/CASK	-0.005	0.048	-9999	-0.48	5	5
ITGA5	0	0	-9999	-10000	0	0
BAX	0.031	0.045	-9999	-10000	0	0
EPB41	0	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.004	0.043	-9999	-0.43	5	5
LAMA3	-0.019	0.12	-9999	-0.74	13	13
EZR	0	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.018	0.11	-9999	-0.74	12	12
Syndecan-2/MMP2	-0.008	0.069	-9999	-0.53	8	8
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	0	0	-9999	-10000	0	0
dendrite morphogenesis	-0.01	0.064	-9999	-0.4	13	13
Syndecan-2/GM-CSF	-0.052	0.15	-9999	-0.48	54	54
determination of left/right symmetry	0.012	0.057	-9999	-0.55	5	5
Syndecan-2/PKC delta	-0.005	0.047	-9999	-0.48	5	5
GNB2L1	0	0	-9999	-10000	0	0
MAPK3	-0.021	0.14	-9999	-0.43	54	54
MAPK1	-0.021	0.14	-9999	-0.43	54	54
Syndecan-2/RACK1	-0.004	0.04	-9999	-0.41	5	5
NF1	0	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.012	0.057	-9999	-0.55	5	5
ITGA2	0	0	-9999	-10000	0	0
MAPK8	0.025	0.05	-9999	-0.47	5	5
Syndecan-2/alpha2/beta1 Integrin	-0.087	0.14	-9999	-0.55	6	6
Syndecan-2/Kininogen	-0.014	0.072	-9999	-0.38	18	18
ITGB1	0	0	-9999	-10000	0	0
SRC	0.028	0.041	-9999	-0.38	5	5
Syndecan-2/CASK/Protein 4.1	-0.004	0.043	-9999	-0.44	5	5
extracellular matrix organization	-0.005	0.047	-9999	-0.47	5	5
actin cytoskeleton reorganization	-0.017	0.092	-9999	-0.5	17	17
Syndecan-2/Caveolin-2/Ras	-0.015	0.082	-9999	-0.46	16	16
Syndecan-2/Laminin alpha3	-0.017	0.093	-9999	-0.5	17	17
Syndecan-2/RasGAP	-0.004	0.038	-9999	-0.38	5	5
alpha5/beta1 Integrin	0	0	-9999	-10000	0	0
PRKCD	0	0	-9999	-10000	0	0
Syndecan-2 dimer	-0.01	0.064	-9999	-0.4	13	13
GO:0007205	0	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	-0.004	0.037	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
SDCBP	0	0	-9999	-10000	0	0
TNFRSF13B	-0.017	0.1	-9999	-0.64	13	13
RASA1	0	0	-9999	-10000	0	0
alpha2/beta1 Integrin	0	0	-9999	-10000	0	0
Syndecan-2/Synbindin	-0.005	0.047	-9999	-0.48	5	5
TGFB1	0	0	-9999	-10000	0	0
CASP3	0.024	0.045	-9999	-0.43	5	5
FN1	-0.019	0.12	-9999	-0.74	13	13
Syndecan-2/IL8	-0.018	0.084	-9999	-0.4	23	23
SDC2	0.012	0.057	-9999	-0.56	5	5
KNG1	-0.015	0.091	-9999	-0.57	13	13
Syndecan-2/Neurofibromin	-0.005	0.047	-9999	-0.48	5	5
TRAPPC4	0	0	-9999	-10000	0	0
CSF2	-0.072	0.22	-9999	-0.74	49	49
Syndecan-2/TGFB1	-0.005	0.047	-9999	-0.48	5	5
Syndecan-2/Syntenin/PI-4-5-P2	-0.004	0.043	-9999	-0.44	5	5
Syndecan-2/Ezrin	-0.004	0.043	-9999	-0.43	5	5
PRKACA	0.024	0.045	-9999	-0.43	5	5
angiogenesis	-0.018	0.084	-9999	-0.4	23	23
MMP2	-0.006	0.066	-9999	-0.74	4	4
IL8	-0.022	0.11	-9999	-0.61	18	18
calcineurin-NFAT signaling pathway	-0.015	0.079	-9999	-0.42	18	18

×

Signaling events mediated by HDAC Class III

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
EP300	0	0	-10000	0	-10000	0	0
HDAC4	0	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.011	0.054	0.42	8	-10000	0	8
CDKN1A	0	0.006	-10000	0	-10000	0	0
KAT2B	-0.001	0.033	-10000	0	-0.74	1	1
BAX	0	0	-10000	0	-10000	0	0
FOXO3	0	0	-10000	0	-10000	0	0
FOXO1	0	0	-10000	0	-10000	0	0
FOXO4	0.02	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0	0	-10000	0	-10000	0	0
TAT	-0.002	0.036	-10000	0	-0.57	2	2
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.048	0.15	-10000	0	-0.42	72	72
PPARGC1A	-0.15	0.3	-10000	0	-0.74	100	100
FHL2	-0.005	0.051	-10000	0	-0.57	4	4
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0	0	-10000	0	-10000	0	0
HIST2H4A	0.011	0.054	-10000	0	-0.42	8	8
SIRT1/FOXO3a	0	0	-10000	0	-10000	0	0
SIRT1	0	0	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0	0	-10000	0	-10000	0	0
SIRT1/Histone H1b	-0.011	0.037	-10000	0	-10000	0	0
apoptosis	0	0	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.097	0.19	-10000	0	-0.48	100	100
p53/SIRT1	-0.001	0.025	-10000	0	-0.56	1	1
SIRT1/FOXO4	0	0	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	-0.003	0.028	-10000	0	-10000	0	0
HIST1H1E	0.004	0.052	-10000	0	-10000	0	0
SIRT1/p300	0	0	-10000	0	-10000	0	0
muscle cell differentiation	0.05	0.12	0.35	72	-10000	0	72
TP53	-0.001	0.033	-10000	0	-0.74	1	1
KU70/SIRT1/BAX	0	0	-10000	0	-10000	0	0
CREBBP	0	0	-10000	0	-10000	0	0
MEF2D	0	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.002	0.026	-10000	0	-0.42	2	2
ACSS2	0.018	0	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	-0.05	0.12	-10000	0	-0.35	72	72

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.002	0.02	-10000	0	-10000	0	0
RFC1	0.002	0.02	-10000	0	-10000	0	0
PRKDC	0.002	0.02	-10000	0	-10000	0	0
RIPK1	0	0.002	-10000	0	-10000	0	0
CASP7	-0.012	0.037	0.26	1	-10000	0	1
FASLG/FAS/FADD/FAF1	-0.018	0.074	0.24	4	-0.34	21	25
MAP2K4	-0.01	0.13	-10000	0	-0.51	7	7
mol:ceramide	-0.006	0.11	-10000	0	-0.43	21	21
GSN	0.002	0.02	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 8	-0.027	0.088	-10000	0	-0.42	19	19
FAS	0.006	0.048	-10000	0	-0.74	2	2
BID	0.003	0.028	0.31	4	-10000	0	4
MAP3K1	0.004	0.079	0.22	1	-10000	0	1
MAP3K7	0.009	0.004	-10000	0	-10000	0	0
RB1	0.001	0.029	-10000	0	-0.47	1	1
CFLAR	0	0.002	-10000	0	-10000	0	0
HGF/MET	-0.11	0.2	-10000	0	-0.48	112	112
ARHGDIB	0.001	0.023	-10000	0	-0.32	1	1
FADD	0.009	0.004	-10000	0	-10000	0	0
actin filament polymerization	-0.002	0.02	-10000	0	-10000	0	0
NFKB1	-0.037	0.078	-10000	0	-0.28	6	6
MAPK8	-0.029	0.19	-10000	0	-0.44	80	80
DFFA	0.002	0.02	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.002	0.02	-10000	0	-10000	0	0
FAS/FADD/MET	-0.005	0.045	-10000	0	-0.45	5	5
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	-0.005	0.071	-10000	0	-0.7	5	5
FAF1	0.009	0.004	-10000	0	-10000	0	0
PARP1	0.002	0.02	-10000	0	-10000	0	0
DFFB	0.002	0.02	-10000	0	-10000	0	0
CHUK	-0.032	0.069	-10000	0	-10000	0	0
FASLG	-0.021	0.15	-10000	0	-0.74	20	20
FAS/FADD	-0.003	0.036	-10000	0	-0.57	2	2
HGF	-0.16	0.3	-10000	0	-0.74	108	108
LMNA	0.002	0.018	-10000	0	-10000	0	0
CASP6	0.002	0.02	-10000	0	-10000	0	0
CASP10	0.007	0.034	-10000	0	-0.74	1	1
CASP3	0.002	0.023	0.24	2	-10000	0	2
PTPN13	-0.004	0.057	-10000	0	-0.74	3	3
CASP8	0.004	0.04	0.43	4	-10000	0	4
IL6	-0.19	0.5	-10000	0	-1.3	82	82
MET	-0.004	0.053	-10000	0	-0.68	3	3
ICAD/CAD	0.002	0.019	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 10	-0.006	0.11	-10000	0	-0.43	21	21
activation of caspase activity by cytochrome c	0.003	0.028	0.31	4	-10000	0	4
PAK2	0.002	0.019	-10000	0	-10000	0	0
BCL2	0.001	0.026	-10000	0	-0.58	1	1

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.057	0.13	-9999	-0.56	7	7
MAP3K8	0.006	0.047	-9999	-0.74	2	2
FOS	0	0.1	-9999	-0.46	7	7
PRKCA	0.007	0.048	-9999	-0.74	2	2
PTPN7	0.008	0.042	-9999	-0.66	2	2
HRAS	0	0	-9999	-10000	0	0
PRKCB	-0.031	0.17	-9999	-0.74	27	27
NRAS	0	0	-9999	-10000	0	0
RAS family/GTP	0	0	-9999	-10000	0	0
MAPK3	0.007	0.063	-9999	-0.45	1	1
MAP2K1	-0.003	0.13	-9999	-0.52	28	28
ELK1	-0.001	0.004	-9999	-10000	0	0
BRAF	-0.032	0.12	-9999	-0.52	28	28
mol:GTP	-0.001	0.002	-9999	-0.006	61	61
MAPK1	0.007	0.063	-9999	-0.45	1	1
RAF1	-0.032	0.12	-9999	-0.52	28	28
KRAS	0	0	-9999	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.034	0.12	-9999	-0.46	37	37
MAP4K1	-0.006	0.066	-9999	-0.74	4	4
MAP3K8	-0.003	0.046	-9999	-0.74	2	2
PRKCB	-0.04	0.17	-9999	-0.74	27	27
DBNL	0	0	-9999	-10000	0	0
CRKL	0	0	-9999	-10000	0	0
MAP3K1	0.015	0.098	-9999	-0.72	3	3
JUN	-0.007	0.16	-9999	-0.66	27	27
MAP3K7	0.015	0.098	-9999	-0.72	3	3
GRAP2	-0.044	0.18	-9999	-0.74	30	30
CRK	0	0	-9999	-10000	0	0
MAP2K4	0.022	0.1	-9999	-0.76	3	3
LAT	0	0	-9999	-10000	0	0
LCP2	-0.009	0.08	-9999	-0.74	6	6
MAPK8	-0.015	0.17	-9999	-0.7	27	27
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.025	0.095	-9999	-0.76	3	3
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.032	0.12	-9999	-0.81	3	3

×

S1P1 pathway

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
VEGFR2 homodimer/VEGFA homodimer	-0.031	0.13	-9999	-0.56	28	28
PDGFRB	0.008	0.034	-9999	-0.74	1	1
SPHK1	-0.008	0.021	-9999	-10000	0	0
mol:S1P	-0.01	0.029	-9999	-10000	0	0
S1P1/S1P/Gi	-0.001	0.14	-9999	-0.59	7	7
GNAO1	0.006	0.05	-9999	-0.64	3	3
PDGFB-D/PDGFRB/PLCgamma1	-0.04	0.1	-9999	-0.5	8	8
PLCG1	0.006	0.13	-9999	-0.54	7	7
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.008	0.034	-9999	-0.74	1	1
GNAI2	0.01	0.004	-9999	-10000	0	0
GNAI3	0.01	0.004	-9999	-10000	0	0
GNAI1	0.008	0.034	-9999	-0.75	1	1
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.013	0.11	-9999	-0.48	28	28
S1P1/S1P	-0.033	0.092	-9999	-0.38	28	28
negative regulation of cAMP metabolic process	0	0.13	-9999	-0.57	7	7
MAPK3	-0.011	0.19	-9999	-0.55	51	51
calcium-dependent phospholipase C activity	-0.001	0.003	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
KDR	-0.041	0.17	-9999	-0.74	28	28
PLCB2	0.003	0.11	-9999	-0.4	15	15
RAC1	0	0	-9999	-10000	0	0
RhoA/GTP	-0.028	0.078	-9999	-0.41	7	7
receptor internalization	-0.031	0.087	-9999	-0.35	28	28
PTGS2	-0.061	0.34	-9999	-1.1	51	51
Rac1/GTP	-0.028	0.078	-9999	-0.41	7	7
RHOA	0	0	-9999	-10000	0	0
VEGFA	0	0.001	-9999	-10000	0	0
negative regulation of T cell proliferation	0	0.13	-9999	-0.57	7	7
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.001	0.082	-9999	-0.74	6	6
MAPK1	-0.011	0.19	-9999	-0.55	51	51
S1P1/S1P/PDGFB-D/PDGFRB	0.005	0.11	-9999	-0.55	7	7
ABCC1	-0.001	0.026	-9999	-0.57	1	1

×

Effects of Botulinum toxin

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
STX1A	0.006	0.039	-9999	-0.42	4	4
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.057	0.17	-9999	-0.56	51	51
STXBP1	-0.006	0.066	-9999	-0.74	4	4
ACh/CHRNA1	-0.014	0.072	-9999	-0.43	14	14
RAB3GAP2/RIMS1/UNC13B	-0.049	0.15	-9999	-0.48	51	51
mol:Ca2+	0	0	-9999	-10000	0	0
UniProt:P30996	0	0	-9999	-10000	0	0
UniProt:Q60393	0	0	-9999	-10000	0	0
CST086	0	0	-9999	-10000	0	0
RIMS1	-0.071	0.22	-9999	-0.73	49	49
mol:ACh	0.005	0.024	-9999	-0.15	11	11
RAB3GAP2	0	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.043	0.12	-9999	-0.61	4	4
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.014	0.072	-9999	-0.42	14	14
UNC13B	-0.004	0.057	-9999	-0.74	3	3
CHRNA1	-0.018	0.1	-9999	-0.63	14	14
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.014	0.07	-9999	-0.39	16	16
SNAP25	-0.001	0.05	-9999	-0.32	11	11
VAMP2	0	0	-9999	-10000	0	0
SYT1	-0.018	0.1	-9999	-0.57	16	16
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.007	0.053	-9999	-0.42	8	8
STX1A/SNAP25 fragment 1/VAMP2	-0.043	0.12	-9999	-0.61	4	4

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	0.014	0.098	-10000	0	-0.47	12	12
IKBKB	0.015	0.052	-10000	0	-0.28	2	2
AKT1	0.004	0.085	0.23	1	-0.27	19	20
IKBKG	0.017	0.055	-10000	0	-0.29	3	3
CALM1	-0.011	0.1	-10000	0	-0.49	14	14
PIK3CA	0	0	-10000	0	-10000	0	0
MAP3K1	0	0.14	-10000	0	-0.68	14	14
MAP3K7	0	0.001	-10000	0	-10000	0	0
mol:Ca2+	-0.018	0.11	-10000	0	-0.52	14	14
DOK1	0	0	-10000	0	-10000	0	0
AP-1	-0.002	0.083	-10000	0	-0.29	7	7
LYN	-0.003	0.047	-10000	0	-0.74	2	2
BLNK	-0.001	0.033	-10000	0	-0.74	1	1
SHC1	0	0	-10000	0	-10000	0	0
BCR complex	-0.03	0.13	-10000	0	-0.56	27	27
CD22	-0.077	0.22	-10000	0	-0.64	51	51
CAMK2G	-0.003	0.094	-10000	0	-0.62	6	6
CSNK2A1	0	0	-10000	0	-10000	0	0
INPP5D	-0.001	0.033	-10000	0	-0.74	1	1
SHC/GRB2/SOS1	-0.021	0.094	-10000	0	-0.73	4	4
GO:0007205	-0.019	0.11	-10000	0	-0.54	14	14
SYK	-0.001	0.033	-10000	0	-0.74	1	1
ELK1	-0.011	0.1	-10000	0	-0.5	14	14
NFATC1	-0.007	0.12	-10000	0	-0.55	16	16
B-cell antigen/BCR complex	-0.03	0.13	-10000	0	-0.56	27	27
PAG1/CSK	-0.008	0.065	-10000	0	-0.56	7	7
NFKBIB	0.014	0.02	0.078	2	-10000	0	2
HRAS	-0.003	0.097	-10000	0	-0.48	14	14
NFKBIA	0.014	0.019	0.078	2	-10000	0	2
NF-kappa-B/RelA/I kappa B beta	0.018	0.016	-10000	0	-10000	0	0
RasGAP/Csk	-0.029	0.12	-10000	0	-0.51	24	24
mol:GDP	-0.021	0.1	-10000	0	-0.51	14	14
PTEN	-0.003	0.046	-10000	0	-0.74	2	2
CD79B	-0.007	0.07	-10000	0	-0.7	5	5
NF-kappa-B/RelA/I kappa B alpha	0.018	0.016	-10000	0	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.015	0.15	-10000	0	-0.57	20	20
PIK3R1	0	0	-10000	0	-10000	0	0
mol:IP3	-0.028	0.11	-10000	0	-0.54	14	14
CSK	0	0	-10000	0	-10000	0	0
FOS	-0.05	0.16	-10000	0	-0.42	65	65
CHUK	0.017	0.055	-10000	0	-0.3	2	2
IBTK	0	0.001	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.023	0.084	-10000	0	-0.59	7	7
PTPN6	-0.071	0.2	-10000	0	-0.82	26	26
RELA	0	0.001	-10000	0	-10000	0	0
BCL2A1	0.015	0.025	-10000	0	-0.12	13	13
VAV2	-0.06	0.17	-10000	0	-0.7	22	22
ubiquitin-dependent protein catabolic process	0.018	0.019	0.081	2	-10000	0	2
BTK	-0.11	0.34	-10000	0	-1.1	49	49
CD19	-0.066	0.18	-10000	0	-0.72	22	22
MAP4K1	-0.006	0.066	-10000	0	-0.74	4	4
CD72	-0.001	0.026	-10000	0	-0.57	1	1
PAG1	-0.01	0.087	-10000	0	-0.74	7	7
MAPK14	0.01	0.12	-10000	0	-0.57	13	13
SH3BP5	-0.012	0.092	-10000	0	-0.74	8	8
PIK3AP1	-0.014	0.13	0.26	4	-0.57	20	24
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.03	0.14	-10000	0	-0.62	21	21
RAF1	0.004	0.092	-10000	0	-0.6	6	6
RasGAP/p62DOK/SHIP	-0.028	0.12	-10000	0	-0.74	8	8
CD79A	-0.034	0.15	-10000	0	-0.68	25	25
re-entry into mitotic cell cycle	-0.002	0.082	0.18	2	-0.29	7	9
RASA1	0	0	-10000	0	-10000	0	0
MAPK3	0.018	0.077	-10000	0	-0.48	6	6
MAPK1	0.018	0.077	-10000	0	-0.48	6	6
CD72/SHP1	-0.065	0.19	-10000	0	-0.75	26	26
NFKB1	0	0.001	-10000	0	-10000	0	0
MAPK8	0.01	0.12	-10000	0	-0.57	13	13
actin cytoskeleton organization	-0.014	0.15	-10000	0	-0.68	15	15
NF-kappa-B/RelA	0.04	0.032	0.16	2	-10000	0	2
Calcineurin	-0.021	0.076	-10000	0	-0.55	6	6
PI3K	-0.063	0.14	-10000	0	-0.61	19	19
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.024	0.1	0.26	4	-0.52	14	18
SOS1	0	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.039	0.16	-10000	0	-0.9	14	14
DAPP1	-0.044	0.18	-10000	0	-1.1	13	13
cytokine secretion	-0.005	0.12	-10000	0	-0.5	16	16
mol:DAG	-0.028	0.11	-10000	0	-0.54	14	14
PLCG2	0	0.001	-10000	0	-10000	0	0
MAP2K1	0.011	0.085	-10000	0	-0.55	6	6
B-cell antigen/BCR complex/FcgammaRIIB	-0.034	0.14	-10000	0	-0.53	32	32
mol:PI-3-4-5-P3	-0.045	0.1	0.32	1	-0.4	19	20
ETS1	-0.004	0.11	-10000	0	-0.57	12	12
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.025	0.11	-10000	0	-0.48	21	21
B-cell antigen/BCR complex/LYN	-0.044	0.17	-10000	0	-0.74	21	21
MALT1	0	0.001	-10000	0	-10000	0	0
TRAF6	0.001	0.003	-10000	0	-10000	0	0
RAC1	-0.017	0.16	-10000	0	-0.74	15	15
B-cell antigen/BCR complex/LYN/SYK	-0.068	0.2	-10000	0	-0.79	26	26
CARD11	-0.013	0.11	-10000	0	-0.54	14	14
FCGR2B	-0.013	0.098	-10000	0	-0.74	9	9
PPP3CA	0	0	-10000	0	-10000	0	0
BCL10	0	0.001	-10000	0	-10000	0	0
IKK complex	0.016	0.026	-10000	0	-10000	0	0
PTPRC	-0.049	0.18	-10000	0	-0.74	33	33
PDPK1	-0.03	0.068	0.21	1	-0.28	13	14
PPP3CB	0	0	-10000	0	-10000	0	0
PPP3CC	0	0	-10000	0	-10000	0	0
POU2F2	0.018	0.013	-10000	0	-0.1	1	1

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.029	0.11	0.45	32	-10000	0	32
KIRREL	-0.004	0.095	-10000	0	-0.75	8	8
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.029	0.11	-10000	0	-0.45	32	32
PLCG1	0	0	-10000	0	-10000	0	0
ARRB2	0	0	-10000	0	-10000	0	0
WASL	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.022	0.085	-10000	0	-0.45	9	9
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.013	0.053	-10000	0	-0.34	8	8
FYN	-0.007	0.085	-10000	0	-0.46	9	9
mol:Ca2+	-0.022	0.085	-10000	0	-0.45	9	9
mol:DAG	-0.022	0.085	-10000	0	-0.45	9	9
NPHS2	-0.003	0.047	-10000	0	-0.58	3	3
mol:IP3	-0.022	0.085	-10000	0	-0.45	9	9
regulation of endocytosis	-0.019	0.075	-10000	0	-0.42	9	9
Nephrin/NEPH1/podocin/Cholesterol	-0.023	0.087	-10000	0	-0.46	9	9
establishment of cell polarity	-0.029	0.11	-10000	0	-0.45	32	32
Nephrin/NEPH1/podocin/NCK1-2	-0.02	0.077	-10000	0	-0.41	9	9
Nephrin/NEPH1/beta Arrestin2	-0.019	0.076	-10000	0	-0.43	9	9
NPHS1	-0.021	0.12	-10000	0	-0.57	24	24
Nephrin/NEPH1/podocin	-0.021	0.082	-10000	0	-0.46	9	9
TJP1	0	0	-10000	0	-10000	0	0
NCK1	0	0	-10000	0	-10000	0	0
NCK2	0	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.022	0.085	-10000	0	-0.45	9	9
CD2AP	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.022	0.085	-10000	0	-0.45	9	9
GRB2	0	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.024	0.14	-10000	0	-0.5	31	31
cytoskeleton organization	-0.016	0.066	-10000	0	-0.41	9	9
Nephrin/NEPH1	-0.021	0.08	-10000	0	-0.32	32	32
Nephrin/NEPH1/ZO-1	-0.023	0.088	-10000	0	-0.46	9	9

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	0	0	-9999	-10000	0	0
epithelial cell differentiation	0	0	-9999	-10000	0	0
CYFIP2	-0.026	0.14	-9999	-0.74	18	18
ENAH	0.058	0.023	-9999	-10000	0	0
EGFR	-0.023	0.12	-9999	-0.63	18	18
EPHA2	-0.004	0.057	-9999	-0.74	3	3
MYO6	0	0	-9999	-10000	0	0
CTNNB1	0	0	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.017	0.089	-9999	-0.48	18	18
AQP5	-0.17	0.25	-9999	-0.55	157	157
CTNND1	0	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.11	0.17	-9999	-0.38	141	141
EGF	-0.014	0.097	-9999	-0.69	10	10
NCKAP1	0	0	-9999	-10000	0	0
AQP3	-0.076	0.19	-9999	-0.55	70	70
cortical microtubule organization	0	0	-9999	-10000	0	0
GO:0000145	0.033	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0	0	-9999	-10000	0	0
MLLT4	0	0	-9999	-10000	0	0
ARF6/GDP	-0.002	0.025	-9999	-10000	0	0
ARF6	0	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.003	0.033	-9999	-0.43	3	3
mol:Ca2+	0	0	-9999	-10000	0	0
VASP	0.044	0	-9999	-10000	0	0
PVRL2	0	0	-9999	-10000	0	0
ZYX	0	0	-9999	-10000	0	0
ARF6/GTP	-0.002	0.03	-9999	-0.4	3	3
CDH1	0	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.017	0.076	-9999	-0.75	1	1
RhoA/GDP	0	0	-9999	-10000	0	0
actin cytoskeleton organization	0.039	0	-9999	-10000	0	0
IGF-1R heterotetramer	0	0	-9999	-10000	0	0
GIT1	0	0	-9999	-10000	0	0
IGF1R	0	0	-9999	-10000	0	0
IGF1	-0.028	0.14	-9999	-0.73	19	19
DIAPH1	-0.023	0.12	-9999	-0.64	18	18
Wnt receptor signaling pathway	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
RhoA/GTP	-0.002	0.024	-9999	-10000	0	0
CTNNA1	0	0	-9999	-10000	0	0
VCL	0.04	0	-9999	-10000	0	0
EFNA1	0	0	-9999	-10000	0	0
LPP	0.04	0	-9999	-10000	0	0
Ephrin A1/EPHA2	-0.002	0.028	-9999	-10000	0	0
SEC6/SEC8	0	0	-9999	-10000	0	0
MGAT3	-0.11	0.17	-9999	-0.39	141	141
HGF/MET	-0.081	0.15	-9999	-10000	0	0
HGF	-0.16	0.3	-9999	-0.74	108	108
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0	0	-9999	-10000	0	0
actin cable formation	0.068	0.029	-9999	-10000	0	0
KIAA1543	0.039	0.018	-9999	-10000	0	0
KIFC3	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
EXOC3	0	0	-9999	-10000	0	0
ACTN1	0	0	-9999	-10000	0	0
NCK1/GIT1	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
EXOC4	0	0	-9999	-10000	0	0
STX4	0	0	-9999	-10000	0	0
PIP5K1C	0	0	-9999	-10000	0	0
LIMA1	0	0	-9999	-10000	0	0
ABI1	0	0	-9999	-10000	0	0
ROCK1	-0.002	0.021	-9999	-10000	0	0
adherens junction assembly	0.053	0.018	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.014	0.069	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
MET	-0.004	0.053	-9999	-0.68	3	3
PLEKHA7	0	0	-9999	-10000	0	0
mol:GTP	-0.003	0.033	-9999	-0.43	3	3
establishment of epithelial cell apical/basal polarity	0	0	-9999	-10000	0	0
cortical actin cytoskeleton stabilization	0	0	-9999	-10000	0	0
regulation of cell-cell adhesion	0.039	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0	0	-9999	-10000	0	0

×

Syndecan-4-mediated signaling events

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
PTK2	0.007	0.1	-9999	-0.61	13	13
Syndecan-4/Syndesmos	0.01	0.075	-9999	-10000	0	0
positive regulation of JNK cascade	-0.048	0.12	-9999	-0.59	12	12
Syndecan-4/ADAM12	-0.06	0.14	-9999	-0.57	2	2
CCL5	-0.013	0.098	-9999	-0.74	9	9
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0	0	-9999	-10000	0	0
ITGA5	0	0	-9999	-10000	0	0
SDCBP	0	0	-9999	-10000	0	0
PLG	-0.007	0.058	-9999	-0.58	5	5
ADAM12	-0.14	0.25	-9999	-0.57	121	121
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.012	0.035	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.075	0.15	-9999	-0.62	2	2
Syndecan-4/CXCL12/CXCR4	-0.051	0.13	-9999	-0.63	12	12
Syndecan-4/Laminin alpha3	0	0.099	-9999	-0.6	2	2
MDK	-0.01	0.076	-9999	-0.57	9	9
Syndecan-4/FZD7	0.01	0.076	-9999	-10000	0	0
Syndecan-4/Midkine	0.005	0.086	-9999	-0.57	1	1
FZD7	-0.001	0.026	-9999	-0.57	1	1
Syndecan-4/FGFR1/FGF	-0.03	0.089	-9999	-0.59	3	3
THBS1	-0.013	0.098	-9999	-0.74	9	9
integrin-mediated signaling pathway	-0.01	0.08	-9999	-10000	0	0
positive regulation of MAPKKK cascade	-0.048	0.12	-9999	-0.59	12	12
Syndecan-4/TACI	0.001	0.091	-9999	-10000	0	0
CXCR4	-0.001	0.033	-9999	-0.74	1	1
cell adhesion	-0.008	0.062	-9999	-0.36	15	15
Syndecan-4/Dynamin	0.01	0.075	-9999	-10000	0	0
Syndecan-4/TSP1	0.003	0.11	-9999	-0.66	8	8
Syndecan-4/GIPC	0.01	0.075	-9999	-10000	0	0
Syndecan-4/RANTES	0.003	0.095	-9999	-0.68	2	2
ITGB1	0	0	-9999	-10000	0	0
LAMA1	-0.17	0.26	-9999	-0.58	146	146
LAMA3	-0.019	0.12	-9999	-0.74	13	13
RAC1	0	0	-9999	-10000	0	0
PRKCA	0.005	0.05	-9999	-0.69	2	2
Syndecan-4/alpha-Actinin	0.01	0.075	-9999	-10000	0	0
TFPI	-0.054	0.19	-9999	-0.74	37	37
F2	-0.015	0.1	-9999	-0.57	16	16
alpha5/beta1 Integrin	0	0	-9999	-10000	0	0
positive regulation of cell adhesion	-0.076	0.16	-9999	-0.64	7	7
ACTN1	0	0	-9999	-10000	0	0
TNC	-0.013	0.087	-9999	-0.59	11	11
Syndecan-4/CXCL12	-0.023	0.15	-9999	-0.65	11	11
FGF6	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
CXCL12	-0.062	0.2	-9999	-0.74	42	42
TNFRSF13B	-0.017	0.1	-9999	-0.64	13	13
FGF2	-0.021	0.12	-9999	-0.74	14	14
FGFR1	-0.001	0.033	-9999	-0.74	1	1
Syndecan-4/PI-4-5-P2	0.004	0.075	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.017	0.12	-9999	-0.72	13	13
cell migration	-0.005	0.014	-9999	-10000	0	0
PRKCD	0.002	0.006	-9999	-10000	0	0
vasculogenesis	-0.01	0.1	-9999	-0.63	8	8
SDC4	0.005	0.078	-9999	-10000	0	0
Syndecan-4/Tenascin C	0.004	0.085	-9999	-10000	0	0
Syndecan-4/PI-4-5-P2/PKC alpha	-0.01	0.027	-9999	-10000	0	0
Syndecan-4/Syntenin	0.01	0.075	-9999	-10000	0	0
MMP9	-0.022	0.14	-9999	-0.58	28	28
Rac1/GTP	-0.009	0.064	-9999	-0.37	15	15
cytoskeleton organization	-0.004	0.07	-9999	-10000	0	0
GIPC1	0	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.019	0.14	-9999	-0.64	7	7

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0	0	-9999	-10000	0	0
SPHK1	0	0	-9999	-10000	0	0
GNAI2	0	0	-9999	-10000	0	0
mol:S1P	0.019	0.008	-9999	-10000	0	0
GNAO1	-0.004	0.049	-9999	-0.63	3	3
mol:Sphinganine-1-P	0.02	0	-9999	-10000	0	0
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0	0.004	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
S1PR3	0	0	-9999	-10000	0	0
S1PR2	0	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	0	0.006	-9999	-10000	0	0
S1PR5	-0.01	0.075	-9999	-0.6	8	8
S1PR4	-0.065	0.21	-9999	-0.74	44	44
GNAI1	-0.001	0.033	-9999	-0.74	1	1
S1P/S1P5/G12	-0.005	0.04	-9999	-0.32	8	8
S1P/S1P3/Gq	-0.069	0.12	-9999	-0.64	2	2
S1P/S1P4/Gi	-0.03	0.092	-9999	-0.31	45	45
GNAQ	-0.001	0.033	-9999	-0.74	1	1
GNAZ	-0.009	0.08	-9999	-0.74	6	6
GNA14	-0.18	0.32	-9999	-0.74	123	123
GNA15	0	0	-9999	-10000	0	0
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
GNA11	0	0	-9999	-10000	0	0
ABCC1	-0.001	0.026	-9999	-0.57	1	1

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.006	0.006	-9999	-10000	0	0
HDAC2	0.006	0.006	-9999	-10000	0	0
GNB1/GNG2	-0.007	0.057	-9999	-0.48	6	6
forebrain development	-0.086	0.14	-9999	-0.49	9	9
GNAO1	0.001	0.05	-9999	-0.63	3	3
SMO/beta Arrestin2	-0.002	0.027	-9999	-0.42	2	2
SMO	0.003	0.038	-9999	-0.58	2	2
ARRB2	0.005	0.005	-9999	-10000	0	0
GLI3/SPOP	0.044	0.015	-9999	-10000	0	0
mol:GTP	-0.003	0.004	-9999	-10000	0	0
GSK3B	0	0	-9999	-10000	0	0
GNAI2	0.005	0.005	-9999	-10000	0	0
SIN3/HDAC complex	0	0.004	-9999	-10000	0	0
GNAI1	0.004	0.034	-9999	-0.74	1	1
XPO1	0.006	0.006	-9999	-10000	0	0
GLI1/Su(fu)	-0.1	0.11	-9999	-0.58	3	3
SAP30	0.006	0.006	-9999	-10000	0	0
mol:GDP	0.003	0.037	-9999	-0.58	2	2
MIM/GLI2A	-0.033	0.05	-9999	-10000	0	0
IFT88	0	0	-9999	-10000	0	0
GNAI3	0.005	0.005	-9999	-10000	0	0
GLI2	0.037	0.023	-9999	-10000	0	0
GLI3	0.04	0.016	-9999	-0.28	1	1
CSNK1D	0	0	-9999	-10000	0	0
CSNK1E	0	0	-9999	-10000	0	0
SAP18	0.006	0.006	-9999	-10000	0	0
embryonic digit morphogenesis	0	0	-9999	-10000	0	0
GNG2	-0.007	0.073	-9999	-0.74	5	5
Gi family/GTP	0.002	0.049	-9999	-0.32	5	5
SIN3B	0.006	0.006	-9999	-10000	0	0
SIN3A	0.006	0.006	-9999	-10000	0	0
GLI3/Su(fu)	-0.001	0.009	-9999	-10000	0	0
GLI2/Su(fu)	0.023	0.033	-9999	-10000	0	0
FOXA2	-0.6	0.6	-9999	-1.2	250	250
neural tube patterning	-0.086	0.14	-9999	-0.49	9	9
SPOP	0	0	-9999	-10000	0	0
Su(fu)/PIAS1	-0.001	0.009	-9999	-10000	0	0
GNB1	-0.001	0.033	-9999	-0.74	1	1
CSNK1G2	0	0	-9999	-10000	0	0
CSNK1G3	0	0	-9999	-10000	0	0
MTSS1	-0.033	0.05	-9999	-10000	0	0
embryonic limb morphogenesis	-0.086	0.14	-9999	-0.49	9	9
SUFU	0.012	0.017	-9999	-10000	0	0
LGALS3	0	0	-9999	-10000	0	0
catabolic process	-0.001	0.013	-9999	-10000	0	0
GLI3A/CBP	0.005	0.033	-9999	-0.38	1	1
KIF3A	0	0	-9999	-10000	0	0
GLI1	-0.088	0.15	-9999	-0.5	9	9
RAB23	0	0	-9999	-10000	0	0
CSNK1A1	0	0	-9999	-10000	0	0
IFT172	0	0	-9999	-10000	0	0
RBBP7	0.006	0.006	-9999	-10000	0	0
Su(fu)/Galectin3	-0.001	0.009	-9999	-10000	0	0
GNAZ	-0.004	0.081	-9999	-0.74	6	6
RBBP4	0.006	0.006	-9999	-10000	0	0
CSNK1G1	0	0	-9999	-10000	0	0
PIAS1	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GLI2/SPOP	0.039	0.021	-9999	-10000	0	0
STK36	0.006	0.006	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.009	0.054	-9999	-0.62	2	2
PTCH1	-0.079	0.16	-9999	-1	6	6
MIM/GLI1	-0.23	0.29	-9999	-0.51	250	250
CREBBP	0.005	0.032	-9999	-0.38	1	1
Su(fu)/SIN3/HDAC complex	0.029	0.029	-9999	-10000	0	0

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	-0.01	0.12	-9999	-0.74	14	14
ELF1	-0.004	0.033	-9999	-0.37	3	3
CCNA2	-0.15	0.25	-9999	-0.57	129	129
PIK3CA	0.01	0	-9999	-10000	0	0
JAK3	0.01	0	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
JAK1	0.01	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.056	0.073	-9999	-0.68	3	3
SHC1	0.01	0	-9999	-10000	0	0
SP1	-0.003	0.033	-9999	-0.37	4	4
IL2RA	0.018	0.083	-9999	-0.69	6	6
IL2RB	0.006	0.058	-9999	-0.74	3	3
SOS1	0.01	0	-9999	-10000	0	0
IL2RG	0	0.088	-9999	-0.74	7	7
G1/S transition of mitotic cell cycle	-0.016	0.12	-9999	-0.9	4	4
PTPN11	0.01	0	-9999	-10000	0	0
CCND2	0.018	0.087	-9999	-0.95	4	4
LCK	0.009	0.033	-9999	-0.74	1	1
GRB2	0.01	0	-9999	-10000	0	0
IL2	0.005	0.005	-9999	-10000	0	0
CDK6	-0.002	0.036	-9999	-0.57	2	2
CCND3	0.06	0.063	-9999	-0.56	3	3

×

S1P4 pathway

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
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.004	0.049	-9999	-0.63	3	3
CDC42/GTP	-0.028	0.086	-9999	-0.47	3	3
PLCG1	0.003	0.099	-9999	-0.48	3	3
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0	0	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
cell migration	-0.028	0.084	-9999	-0.46	3	3
S1PR5	-0.01	0.075	-9999	-0.6	8	8
S1PR4	-0.065	0.21	-9999	-0.74	44	44
MAPK3	0.003	0.099	-9999	-0.48	3	3
MAPK1	0.003	0.099	-9999	-0.48	3	3
S1P/S1P5/Gi	-0.007	0.04	-9999	-0.31	2	2
GNAI1	-0.001	0.033	-9999	-0.74	1	1
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.006	0.047	-9999	-0.37	8	8
RHOA	-0.01	0.12	-9999	-0.4	44	44
S1P/S1P4/Gi	-0.032	0.096	-9999	-0.32	45	45
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.009	0.08	-9999	-0.74	6	6
S1P/S1P4/G12/G13	-0.038	0.12	-9999	-0.44	44	44
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0

×

Signaling events mediated by PTP1B

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
PDGFRB	-0.001	0.033	-10000	0	-0.74	1	1
Jak2/Leptin Receptor	-0.026	0.097	-10000	0	-0.38	28	28
PTP1B/AKT1	-0.006	0.023	-10000	0	-10000	0	0
FYN	-0.001	0.033	-10000	0	-0.74	1	1
p210 bcr-abl/PTP1B	0.024	0.036	-10000	0	-0.31	1	1
EGFR	-0.013	0.12	-10000	0	-0.63	18	18
EGF/EGFR	-0.02	0.084	-10000	0	-0.48	12	12
CSF1	-0.006	0.066	-10000	0	-0.74	4	4
AKT1	0.009	0.003	-10000	0	-10000	0	0
INSR	0.009	0.003	-10000	0	-10000	0	0
PTP1B/N-cadherin	0.01	0.085	-10000	0	-0.36	15	15
Insulin Receptor/Insulin	-0.004	0.018	-10000	0	-10000	0	0
HCK	-0.009	0.08	-10000	0	-0.74	6	6
CRK	0	0	-10000	0	-10000	0	0
TYK2	0.029	0.034	-10000	0	-10000	0	0
EGF	-0.004	0.099	-10000	0	-0.69	10	10
YES1	0	0	-10000	0	-10000	0	0
CAV1	-0.024	0.11	-10000	0	-0.46	10	10
TXN	0.008	0.005	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.005	0.021	-10000	0	-10000	0	0
cell migration	-0.024	0.036	0.31	1	-10000	0	1
STAT3	0.007	0.005	-10000	0	-10000	0	0
PRLR	-0.04	0.16	-10000	0	-0.63	32	32
ITGA2B	-0.022	0.13	-10000	0	-0.74	15	15
CSF1R	-0.015	0.1	-10000	0	-0.74	10	10
Prolactin Receptor/Prolactin	-0.036	0.13	-10000	0	-0.47	39	39
FGR	-0.054	0.19	-10000	0	-0.74	37	37
PTP1B/p130 Cas	0.027	0.033	-10000	0	-10000	0	0
Crk/p130 Cas	-0.005	0.021	-10000	0	-10000	0	0
DOK1	0.033	0.035	-10000	0	-0.33	1	1
JAK2	0.014	0.05	-10000	0	-0.32	2	2
Jak2/Leptin Receptor/Leptin	-0.045	0.084	-10000	0	-0.47	3	3
PIK3R1	0	0	-10000	0	-10000	0	0
PTPN1	0.024	0.036	-10000	0	-0.31	1	1
LYN	-0.003	0.046	-10000	0	-0.74	2	2
CDH2	-0.033	0.14	-10000	0	-0.59	28	28
SRC	0.023	0.015	-10000	0	-10000	0	0
ITGB3	-0.016	0.11	-10000	0	-0.74	11	11
CAT1/PTP1B	0.015	0.12	-10000	0	-0.52	16	16
CAPN1	0.007	0.005	-10000	0	-10000	0	0
CSK	0	0	-10000	0	-10000	0	0
PI3K	-0.003	0.014	-10000	0	-10000	0	0
mol:H2O2	0	0.002	-10000	0	-10000	0	0
STAT3 (dimer)	-0.041	0.077	-10000	0	-0.54	2	2
negative regulation of transcription	0.014	0.05	-10000	0	-0.31	2	2
FCGR2A	-0.015	0.1	-10000	0	-0.74	10	10
FER	0.008	0.005	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.029	0.12	-10000	0	-0.56	26	26
BLK	-0.036	0.15	-10000	0	-0.66	27	27
Insulin Receptor/Insulin/Shc	0	0	-10000	0	-10000	0	0
RHOA	0.007	0.005	-10000	0	-10000	0	0
LEPR	-0.038	0.17	-10000	0	-0.74	28	28
BCAR1	0	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0	0	-10000	0	-10000	0	0
mol:NADPH	0	0.002	-10000	0	-10000	0	0
TRPV6	-0.003	0.14	-10000	0	-0.63	17	17
PRL	-0.009	0.072	-10000	0	-0.58	8	8
SOCS3	0.003	0.091	-10000	0	-1.4	2	2
SPRY2	0.004	0.048	-10000	0	-0.74	2	2
Insulin Receptor/Insulin/IRS1	0	0	-10000	0	-10000	0	0
CSF1/CSF1R	-0.016	0.075	-10000	0	-0.45	12	12
Ras protein signal transduction	0.005	0.012	-10000	0	-10000	0	0
IRS1	0	0	-10000	0	-10000	0	0
INS	0.001	0.001	-10000	0	-10000	0	0
LEP	-0.1	0.23	-10000	0	-0.57	94	94
STAT5B	0.022	0.037	-10000	0	-0.25	1	1
STAT5A	0.022	0.037	-10000	0	-0.25	1	1
GRB2	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.027	0.04	-10000	0	-0.47	1	1
CSN2	-0.012	0.041	-10000	0	-10000	0	0
PIK3CA	0	0	-10000	0	-10000	0	0
LAT	0.013	0.073	-10000	0	-0.48	10	10
YBX1	0.012	0.007	-10000	0	-10000	0	0
LCK	-0.001	0.033	-10000	0	-0.74	1	1
SHC1	0	0	-10000	0	-10000	0	0
NOX4	0.004	0.037	-10000	0	-0.57	2	2

×

TRAIL signaling 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
TNFSF10	0	0	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	-0.029	0.12	-10000	0	-0.55	26	26
MAP2K4	0.041	0.011	-10000	0	-10000	0	0
IKBKB	-0.001	0.026	-10000	0	-0.57	1	1
TNFRSF10B	0	0	-10000	0	-10000	0	0
TNFRSF10A	-0.003	0.046	-10000	0	-0.74	2	2
SMPD1	0	0	-10000	0	-10000	0	0
IKBKG	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	-0.038	0.16	-10000	0	-0.74	26	26
TRAIL/TRAILR2	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR3	-0.072	0.19	-10000	0	-0.56	65	65
TRAIL/TRAILR1	-0.002	0.035	-10000	0	-0.56	2	2
TRAIL/TRAILR4	-0.029	0.12	-10000	0	-0.56	26	26
TRAIL/TRAILR1/DAP3/GTP	-0.002	0.028	-10000	0	-0.44	2	2
IKK complex	-0.001	0.009	-10000	0	-10000	0	0
RIPK1	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0	0	-10000	0	-10000	0	0
MAPK3	0.02	0	-10000	0	-10000	0	0
MAP3K1	-0.001	0.009	-10000	0	-10000	0	0
TRAILR4 (trimer)	-0.038	0.16	-10000	0	-0.74	26	26
TRADD	0	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	-0.003	0.046	-10000	0	-0.74	2	2
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.001	0.019	-10000	0	-10000	0	0
CFLAR	0	0	-10000	0	-10000	0	0
MAPK1	0.02	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.002	0.025	-10000	0	-0.4	2	2
mol:ceramide	0	0	-10000	0	-10000	0	0
FADD	0	0	-10000	0	-10000	0	0
MAPK8	0.046	0.01	-10000	0	-10000	0	0
TRAF2	0	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	-0.095	0.25	-10000	0	-0.74	65	65
CHUK	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.002	0.03	-10000	0	-0.48	2	2
DAP3	0	0	-10000	0	-10000	0	0
CASP10	0.014	0.067	0.29	25	-0.39	1	26
JNK cascade	-0.029	0.12	-10000	0	-0.55	26	26
TRAIL (trimer)	0	0	-10000	0	-10000	0	0
TNFRSF10C	-0.096	0.25	-10000	0	-0.74	65	65
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.002	0.026	-10000	0	-0.41	2	2
TRAIL/TRAILR2/FADD	0	0	-10000	0	-10000	0	0
cell death	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0	0	-10000	0	-10000	0	0
TRAILR2 (trimer)	0	0	-10000	0	-10000	0	0
CASP8	0	0.003	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0	0	-10000	0	-10000	0	0

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	-0.003	0.046	-10000	0	-0.74	2	2
ANTXR2	-0.01	0.087	-10000	0	-0.74	7	7
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.001	0.013	-10000	0	-0.1	7	7
monocyte activation	-0.002	0.082	-10000	0	-0.45	16	16
MAP2K2	-0.001	0.005	-10000	0	-10000	0	0
MAP2K1	-0.001	0.011	-10000	0	-10000	0	0
MAP2K7	-0.001	0.011	-10000	0	-10000	0	0
MAP2K6	-0.002	0.017	-10000	0	-0.31	1	1
CYAA	0.006	0.067	-10000	0	-0.53	7	7
MAP2K4	-0.001	0.011	-10000	0	-10000	0	0
IL1B	0.004	0.072	-10000	0	-0.44	12	12
Channel	-0.008	0.07	-10000	0	-0.56	7	7
NLRP1	-0.004	0.037	-10000	0	-0.47	3	3
CALM1	0	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.002	0.015	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.001	0.013	0.1	7	-10000	0	7
MAPK3	-0.001	0.011	-10000	0	-10000	0	0
MAPK1	-0.001	0.011	-10000	0	-10000	0	0
PGR	-0.092	0.18	-10000	0	-0.43	106	106
PA/Cellular Receptors	-0.008	0.075	-10000	0	-0.61	7	7
apoptosis	-0.001	0.013	-10000	0	-0.1	7	7
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.007	0.066	-10000	0	-0.53	7	7
macrophage activation	0.017	0.012	-10000	0	-10000	0	0
TNF	-0.019	0.12	-10000	0	-0.72	13	13
VCAM1	-0.016	0.08	-10000	0	-0.45	16	16
platelet activation	-0.002	0.015	-10000	0	-10000	0	0
MAPKKK cascade	-0.013	0.013	0.12	2	-10000	0	2
IL18	0.011	0.045	-10000	0	-0.45	4	4
negative regulation of macrophage activation	-0.001	0.013	-10000	0	-0.1	7	7
LEF	-0.001	0.013	-10000	0	-0.1	7	7
CASP1	-0.003	0.031	-10000	0	-0.28	4	4
mol:cAMP	-0.002	0.015	-10000	0	-10000	0	0
necrosis	-0.001	0.013	-10000	0	-0.1	7	7
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.008	0.067	-10000	0	-0.54	7	7
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0	0	-9999	-10000	0	0
HDAC3	0	0	-9999	-10000	0	0
VDR	-0.001	0.033	-9999	-0.74	1	1
Cbp/p300/PCAF	-0.001	0.021	-9999	-0.48	1	1
EP300	0	0	-9999	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.034	0.028	-9999	-0.31	1	1
KAT2B	-0.001	0.033	-9999	-0.74	1	1
MAPK14	0	0	-9999	-10000	0	0
AKT1	0.02	0.037	-9999	-0.31	3	3
RAR alpha/9cRA/Cyclin H	-0.007	0.029	-9999	-10000	0	0
mol:9cRA	0	0	-9999	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.032	0.033	-9999	-0.41	1	1
CDC2	0.001	0	-9999	-10000	0	0
response to UV	0.001	0	-9999	-10000	0	0
RAR alpha/Jnk1	-0.008	0.03	-9999	-10000	0	0
NCOR2	-0.001	0.033	-9999	-0.74	1	1
VDR/VDR/Vit D3	-0.001	0.025	-9999	-0.56	1	1
RXRs/RARs/NRIP1/9cRA	-0.024	0.083	-9999	-0.6	2	2
NCOA2	-0.001	0.033	-9999	-0.74	1	1
NCOA3	0	0	-9999	-10000	0	0
NCOA1	0	0	-9999	-10000	0	0
VDR/VDR/DNA	-0.001	0.033	-9999	-0.74	1	1
RARG	0.01	0	-9999	-10000	0	0
RAR gamma1/9cRA	0	0	-9999	-10000	0	0
MAPK3	0.01	0	-9999	-10000	0	0
MAPK1	0	0	-9999	-10000	0	0
MAPK8	0.011	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.065	0.072	-9999	-0.66	2	2
RARA	0.014	0.043	-9999	-0.29	2	2
negative regulation of phosphoinositide 3-kinase cascade	0	0	-9999	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.031	0.035	-9999	-0.41	1	1
PRKCA	0.01	0.047	-9999	-0.74	2	2
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.041	0.091	-9999	-0.63	2	2
RXRG	-0.22	0.22	-9999	-0.42	266	266
RXRA	0.021	0.041	-9999	-0.31	2	2
RXRB	0.006	0.065	-9999	-0.41	2	2
VDR/Vit D3/DNA	-0.001	0.025	-9999	-0.56	1	1
RBP1	-0.021	0.11	-9999	-0.57	18	18
CRBP1/9-cic-RA	-0.015	0.079	-9999	-0.42	18	18
RARB	0.007	0.058	-9999	-0.74	3	3
PRKCG	-0.031	0.15	-9999	-0.57	36	36
MNAT1	0	0	-9999	-10000	0	0
RAR alpha/RXRs	-0.031	0.082	-9999	-0.66	2	2
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.013	0.071	-9999	-0.5	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.034	0.038	-9999	-0.4	1	1
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.041	0.091	-9999	-0.63	2	2
positive regulation of DNA binding	-0.006	0.027	-9999	-10000	0	0
NRIP1	-0.037	0.085	-9999	-0.69	1	1
RXRs/RARs	-0.048	0.092	-9999	-0.63	2	2
RXRs/RXRs/DNA/9cRA	-0.07	0.075	-9999	-0.69	2	2
PRKACA	0	0	-9999	-10000	0	0
CDK7	0	0	-9999	-10000	0	0
TFIIH	0	0	-9999	-10000	0	0
RAR alpha/9cRA	-0.005	0.018	-9999	-10000	0	0
CCNH	0	0	-9999	-10000	0	0
CREBBP	0	0	-9999	-10000	0	0
RAR gamma2/9cRA	0	0	-9999	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.001	0.026	-9999	-0.57	1	1
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	-0.001	0.018	-9999	-0.26	2	2
response to UV	0	0	-9999	-10000	0	0
YES1	0	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	0	-9999	-10000	0	0
FYN	-0.001	0.033	-9999	-0.74	1	1
MAP3K12	0	0	-9999	-10000	0	0
FGR	-0.054	0.19	-9999	-0.74	37	37
p38 alpha/TAB1	-0.013	0.05	-9999	-0.42	3	3
PRKG1	-0.068	0.21	-9999	-0.74	46	46
DUSP8	-0.015	0.1	-9999	-0.74	10	10
PGK/cGMP/p38 alpha	-0.043	0.12	-9999	-0.38	46	46
apoptosis	-0.013	0.048	-9999	-0.4	3	3
RAL/GTP	0	0	-9999	-10000	0	0
LYN	-0.003	0.046	-9999	-0.74	2	2
DUSP1	-0.087	0.24	-9999	-0.74	59	59
PAK1	-0.001	0.026	-9999	-0.57	1	1
SRC	0	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0	0	-9999	-10000	0	0
TRAF6	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.03	0.087	-9999	-0.38	12	12
BLK	-0.036	0.15	-9999	-0.66	27	27
HCK	-0.009	0.08	-9999	-0.74	6	6
MAP2K3	0	0	-9999	-10000	0	0
DUSP16	0	0	-9999	-10000	0	0
DUSP10	-0.001	0.033	-9999	-0.74	1	1
TRAF6/MEKK3	0	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.032	0.067	-9999	-0.45	3	3
positive regulation of innate immune response	0.036	0.094	-9999	-0.4	13	13
LCK	-0.001	0.033	-9999	-0.74	1	1
p38alpha-beta/MKP7	-0.02	0.072	-9999	-0.44	6	6
p38alpha-beta/MKP5	-0.021	0.075	-9999	-0.46	7	7
PGK/cGMP	-0.052	0.16	-9999	-0.56	46	46
PAK2	0	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.056	0.13	-9999	-0.52	17	17
CDC42	0	0	-9999	-10000	0	0
RALB	0	0	-9999	-10000	0	0
RALA	0	0	-9999	-10000	0	0
PAK3	-0.004	0.053	-9999	-0.68	3	3

×

LPA receptor mediated events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.009	0.079	-9999	-0.66	6	6
NF kappa B1 p50/RelA/I kappa B alpha	-0.017	0.046	-9999	-10000	0	0
AP1	-0.056	0.14	-9999	-0.51	8	8
mol:PIP3	-0.02	0.077	-9999	-0.58	3	3
AKT1	-0.006	0.05	-9999	-0.57	3	3
PTK2B	0.017	0.037	-9999	-0.34	2	2
RHOA	0.027	0.02	-9999	-10000	0	0
PIK3CB	0	0.001	-9999	-10000	0	0
mol:Ca2+	0	0.081	-9999	-0.45	3	3
MAGI3	-0.001	0.033	-9999	-0.74	1	1
RELA	0	0	-9999	-10000	0	0
apoptosis	-0.011	0.057	-9999	-0.41	6	6
HRAS/GDP	0	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.024	0.06	-9999	-0.39	8	8
NF kappa B1 p50/RelA	-0.023	0.065	-9999	-0.64	1	1
endothelial cell migration	0.016	0.087	-9999	-0.82	5	5
ADCY4	0.017	0.097	-9999	-0.61	6	6
ADCY5	0.012	0.094	-9999	-0.66	4	4
ADCY6	0.031	0.069	-9999	-0.59	4	4
ADCY7	0.032	0.067	-9999	-0.66	3	3
ADCY1	0.032	0.068	-9999	-0.66	3	3
ADCY2	0.018	0.081	-9999	-0.6	4	4
ADCY3	0.032	0.067	-9999	-0.66	3	3
ADCY8	-0.036	0.12	-9999	-0.65	5	5
ADCY9	0.031	0.072	-9999	-0.65	4	4
GSK3B	0.024	0.035	-9999	-0.38	1	1
arachidonic acid secretion	0.035	0.069	-9999	-0.58	4	4
GNG2	-0.007	0.073	-9999	-0.74	5	5
TRIP6	0	0.004	-9999	-10000	0	0
GNAO1	0.018	0.062	-9999	-0.54	5	5
HRAS	0	0	-9999	-10000	0	0
NFKBIA	0.017	0.073	-9999	-10000	0	0
GAB1	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.003	0.058	-9999	-0.92	2	2
JUN	0	0	-9999	-10000	0	0
LPA/LPA2/NHERF2	-0.003	0.038	-9999	-0.48	3	3
TIAM1	-0.004	0.069	-9999	-1.1	2	2
PIK3R1	0	0.001	-9999	-10000	0	0
mol:IP3	-0.001	0.082	-9999	-0.46	3	3
PLCB3	0.022	0.036	-9999	-0.43	3	3
FOS	-0.09	0.24	-9999	-0.74	61	61
positive regulation of mitosis	0.035	0.069	-9999	-0.58	4	4
LPA/LPA1-2-3	-0.013	0.071	-9999	-0.48	6	6
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
stress fiber formation	0.025	0.047	-9999	-0.42	2	2
GNAZ	0.014	0.073	-9999	-0.52	8	8
EGFR/PI3K-beta/Gab1	-0.02	0.08	-9999	-0.61	3	3
positive regulation of dendritic cell cytokine production	-0.013	0.071	-9999	-0.48	6	6
LPA/LPA2/MAGI-3	-0.002	0.023	-9999	-0.48	1	1
ARHGEF1	-0.003	0.04	-9999	-0.54	2	2
GNAI2	0.02	0.049	-9999	-0.64	2	2
GNAI3	0.02	0.049	-9999	-0.64	2	2
GNAI1	0.019	0.064	-9999	-0.84	2	2
LPA/LPA3	-0.014	0.077	-9999	-0.46	14	14
LPA/LPA2	-0.001	0.01	-9999	-10000	0	0
LPA/LPA1	-0.005	0.054	-9999	-0.5	5	5
HB-EGF/EGFR	-0.05	0.14	-9999	-0.41	61	61
HBEGF	-0.025	0.14	-9999	-0.48	45	45
mol:DAG	-0.001	0.082	-9999	-0.46	3	3
cAMP biosynthetic process	0.02	0.075	-9999	-0.66	4	4
NFKB1	0	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
GNB1	-0.001	0.033	-9999	-0.74	1	1
LYN	0.015	0.084	-9999	-0.64	2	2
GNAQ	-0.009	0.05	-9999	-0.38	5	5
LPAR2	0	0.001	-9999	-10000	0	0
LPAR3	-0.017	0.1	-9999	-0.62	14	14
LPAR1	-0.004	0.055	-9999	-0.83	2	2
IL8	0.001	0.13	-9999	-0.46	14	14
PTK2	0.021	0.072	-9999	-0.45	6	6
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.011	0.058	-9999	-0.41	6	6
EGFR	-0.015	0.12	-9999	-0.63	18	18
PLCG1	-0.016	0.084	-9999	-0.36	10	10
PLD2	0.021	0.072	-9999	-0.45	6	6
G12/G13	-0.004	0.043	-9999	-0.58	2	2
PI3K-beta	-0.007	0.061	-9999	-0.69	3	3
cell migration	0.002	0.032	-9999	-0.26	2	2
SLC9A3R2	-0.004	0.057	-9999	-0.74	3	3
PXN	0.025	0.048	-9999	-0.43	2	2
HRAS/GTP	-0.009	0.066	-9999	-0.61	4	4
RAC1	0	0	-9999	-10000	0	0
MMP9	-0.032	0.13	-9999	-0.57	28	28
PRKCE	0.008	0.033	-9999	-0.74	1	1
PRKCD	0.006	0.079	-9999	-0.47	2	2
Gi(beta/gamma)	-0.01	0.078	-9999	-0.65	5	5
mol:LPA	-0.001	0.016	-9999	-0.21	3	3
TRIP6/p130 Cas/FAK1/Paxillin	-0.001	0.059	-9999	-0.64	1	1
MAPKKK cascade	0.035	0.069	-9999	-0.58	4	4
contractile ring contraction involved in cytokinesis	0.027	0.019	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.1	0.17	-9999	-0.39	127	127
GNA15	-0.008	0.047	-9999	-0.38	4	4
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
MAPT	0.024	0.061	-9999	-0.4	8	8
GNA11	-0.008	0.047	-9999	-0.38	4	4
Rac1/GTP	-0.004	0.062	-9999	-0.98	2	2
MMP2	0.016	0.088	-9999	-0.83	5	5

×

S1P3 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
PDGFRB	-0.001	0.033	-9999	-0.74	1	1
mol:S1P	0.001	0.003	-9999	-10000	0	0
S1P1/S1P/Gi	-0.006	0.039	-9999	-0.31	7	7
GNAO1	0.007	0.05	-9999	-0.63	3	3
S1P/S1P3/G12/G13	0	0.001	-9999	-10000	0	0
AKT1	-0.003	0.024	-9999	-0.46	1	1
AKT3	0.036	0.1	-9999	-1.3	3	3
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.001	0.033	-9999	-0.74	1	1
GNAI2	0.011	0.002	-9999	-10000	0	0
GNAI3	0.011	0.002	-9999	-10000	0	0
GNAI1	0.01	0.033	-9999	-0.74	1	1
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.011	0.002	-9999	-10000	0	0
S1PR2	0	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.033	0.043	-9999	-10000	0	0
MAPK3	0.038	0.041	-9999	-10000	0	0
MAPK1	0.038	0.041	-9999	-10000	0	0
JAK2	0.041	0.044	-9999	-0.43	1	1
CXCR4	0.038	0.049	-9999	-0.63	1	1
FLT1	0.012	0.001	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.038	0.041	-9999	-10000	0	0
S1P/S1P3/Gi	0.033	0.043	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
RhoA/GTP	-0.005	0.033	-9999	-10000	0	0
VEGFA	0.012	0.001	-9999	-10000	0	0
S1P/S1P2/Gi	0.03	0.04	-9999	-0.3	1	1
VEGFR1 homodimer/VEGFA homodimer	0.022	0.005	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.078	0.14	-9999	-0.32	123	123
GNAQ	-0.001	0.033	-9999	-0.74	1	1
GNAZ	0.002	0.081	-9999	-0.74	6	6
G12/G13	0	0	-9999	-10000	0	0
GNA14	-0.18	0.32	-9999	-0.74	123	123
GNA15	0	0	-9999	-10000	0	0
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
GNA11	0	0	-9999	-10000	0	0
Rac1/GTP	-0.005	0.033	-9999	-10000	0	0

×

Signaling events mediated by PRL

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
CCNE1	-0.13	0.24	-9999	-0.57	111	111
mol:Halofuginone	0	0	-9999	-10000	0	0
ITGA1	-0.009	0.08	-9999	-0.74	6	6
CDKN1A	-0.004	0.024	-9999	-10000	0	0
PRL-3/alpha Tubulin	0	0	-9999	-10000	0	0
mol:Ca2+	-0.028	0.12	-9999	-0.56	25	25
AGT	-0.036	0.16	-9999	-0.73	25	25
CCNA2	-0.054	0.16	-9999	-0.69	4	4
TUBA1B	0	0	-9999	-10000	0	0
EGR1	0.008	0.084	-9999	-0.55	11	11
CDK2/Cyclin E1	-0.063	0.12	-9999	-0.43	3	3
MAPK3	0.02	0	-9999	-10000	0	0
PRL-2 /Rab GGTase beta	0	0	-9999	-10000	0	0
MAPK1	0.02	0	-9999	-10000	0	0
PTP4A1	0.023	0.067	-9999	-10000	0	0
PTP4A3	0	0	-9999	-10000	0	0
PTP4A2	0	0	-9999	-10000	0	0
ITGB1	0.02	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
RAC1	-0.004	0.024	-9999	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0	0	-9999	-10000	0	0
PRL-1/ATF-5	-0.012	0.065	-9999	-10000	0	0
RABGGTA	0	0	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
RHOC	-0.004	0.024	-9999	-10000	0	0
RHOA	-0.004	0.024	-9999	-10000	0	0
cell motility	0.028	0.031	-9999	-10000	0	0
PRL-1/alpha Tubulin	-0.009	0.057	-9999	-10000	0	0
PRL-3/alpha1 Integrin	-0.007	0.06	-9999	-0.56	6	6
ROCK1	0.028	0.031	-9999	-10000	0	0
RABGGTB	0	0	-9999	-10000	0	0
CDK2	0	0	-9999	-10000	0	0
mitosis	0.023	0.066	-9999	-0.42	11	11
ATF5	-0.008	0.068	-9999	-0.57	7	7

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0	0	-10000	0	-10000	0	0
ATM	0	0	-10000	0	-10000	0	0
UBE2D3	0	0	-10000	0	-10000	0	0
PRKDC	0	0	-10000	0	-10000	0	0
ATR	0	0	-10000	0	-10000	0	0
UBE2L3	0	0	-10000	0	-10000	0	0
FANCD2	0.022	0	-10000	0	-10000	0	0
protein ubiquitination	-0.062	0.12	-10000	0	-10000	0	0
XRCC5	0	0	-10000	0	-10000	0	0
XRCC6	0	0	-10000	0	-10000	0	0
M/R/N Complex	0	0	-10000	0	-10000	0	0
MRE11A	0	0	-10000	0	-10000	0	0
DNA-PK	0	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	-0.002	0.012	-10000	0	-10000	0	0
FANCF	0	0	-10000	0	-10000	0	0
BRCA1	0	0	-10000	0	-10000	0	0
CCNE1	-0.13	0.24	-10000	0	-0.57	111	111
CDK2/Cyclin E1	-0.092	0.17	-10000	0	-0.42	111	111
FANCG	-0.002	0.036	-10000	0	-0.57	2	2
BRCA1/BACH1/BARD1	0	0	-10000	0	-10000	0	0
FANCE	0	0	-10000	0	-10000	0	0
FANCC	0	0	-10000	0	-10000	0	0
NBN	0	0	-10000	0	-10000	0	0
FANCA	-0.002	0.036	-10000	0	-0.57	2	2
DNA repair	0.007	0.1	-10000	0	-10000	0	0
BRCA1/BARD1/ubiquitin	0	0	-10000	0	-10000	0	0
BARD1/DNA-PK	0	0	-10000	0	-10000	0	0
FANCL	-0.001	0.026	-10000	0	-0.57	1	1
mRNA polyadenylation	0	0	-10000	0	-10000	0	0
BRCA1/BARD1/CTIP/M/R/N Complex	0	0.005	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1/TopBP1	0	0	-10000	0	-10000	0	0
BRCA1/BARD1/P53	-0.001	0.019	-10000	0	-0.43	1	1
BARD1/CSTF1/BRCA1	0	0	-10000	0	-10000	0	0
BRCA1/BACH1	0	0	-10000	0	-10000	0	0
BARD1	0	0	-10000	0	-10000	0	0
PCNA	0	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	0	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH7	0	0	-10000	0	-10000	0	0
BRCA1/BARD1/RAD51/PCNA	-0.044	0.11	-10000	0	-10000	0	0
BARD1/DNA-PK/P53	-0.001	0.018	-10000	0	-0.4	1	1
BRCA1/BARD1/Ubiquitin	0	0	-10000	0	-10000	0	0
BRCA1/BARD1/CTIP	-0.001	0.014	-10000	0	-10000	0	0
FA complex	-0.001	0.016	-10000	0	-10000	0	0
BARD1/EWS	0	0	-10000	0	-10000	0	0
RBBP8	0.019	0.019	-10000	0	-0.42	1	1
TP53	-0.001	0.033	-10000	0	-0.74	1	1
TOPBP1	0	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.001	0.019	0.43	1	-10000	0	1
BRCA1/BARD1	-0.063	0.12	-10000	0	-10000	0	0
CSTF1	0	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0	0	-10000	0	-10000	0	0
CDK2	0	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.083	0.2	-10000	0	-0.57	72	72
RAD50	0	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0	0	-10000	0	-10000	0	0
EWSR1	0	0	-10000	0	-10000	0	0

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.05	0.056	-10000	0	-0.82	1	1
UGCG	-0.002	0.009	-10000	0	-10000	0	0
AKT1/mTOR/p70S6K/Hsp90/TERT	0.034	0.067	-10000	0	-0.46	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.024	0.015	-10000	0	-10000	0	0
mol:DAG	0	0.002	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.007	0.042	-10000	0	-0.48	3	3
FRAP1	0.072	0.066	-10000	0	-0.56	3	3
FOXO3	0.074	0.063	-10000	0	-0.55	3	3
AKT1	0.069	0.067	-10000	0	-0.6	3	3
GAB2	-0.01	0.12	-10000	0	-0.74	14	14
SMPD1	-0.002	0.009	-10000	0	-10000	0	0
SGMS1	-0.002	0.009	-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	0.02	0.001	-10000	0	-10000	0	0
CALM1	0	0	-10000	0	-10000	0	0
cell proliferation	0.045	0.029	-10000	0	-10000	0	0
EIF3A	0	0	-10000	0	-10000	0	0
PI3K	0	0	-10000	0	-10000	0	0
RPS6KB1	0.022	0.026	-10000	0	-0.26	1	1
mol:sphingomyelin	0	0.002	-10000	0	-10000	0	0
natural killer cell activation	0.001	0	-10000	0	-10000	0	0
JAK3	0.013	0.001	-10000	0	-10000	0	0
PIK3R1	0.013	0.001	-10000	0	-10000	0	0
JAK1	0.013	0.001	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
MYC	0.072	0.058	-10000	0	-0.48	3	3
MYB	0.015	0.1	-10000	0	-1.3	2	2
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.059	0.074	-10000	0	-0.68	3	3
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.003	0.017	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.059	0.072	-10000	0	-0.65	3	3
Rac1/GDP	0	0	-10000	0	-10000	0	0
T cell proliferation	0.065	0.067	-10000	0	-0.6	3	3
SHC1	0.01	0.002	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.003	0.008	-10000	0	-0.04	17	17
PRKCZ	0.065	0.069	-10000	0	-0.63	3	3
NF kappa B1 p50/RelA	-0.007	0.042	-10000	0	-0.47	3	3
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.044	0.061	-10000	0	-0.64	3	3
HSP90AA1	0	0	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
IL2RA	0.002	0.073	-10000	0	-0.66	6	6
IL2RB	0.008	0.058	-10000	0	-0.74	3	3
TERT	-0.23	0.28	-10000	0	-0.57	197	197
E2F1	0.019	0.047	-10000	0	-0.45	2	2
SOS1	0.01	0.002	-10000	0	-10000	0	0
RPS6	0	0	-10000	0	-10000	0	0
mol:cAMP	-0.002	0.004	0.019	17	-10000	0	17
PTPN11	0.011	0.002	-10000	0	-10000	0	0
IL2RG	0.002	0.088	-10000	0	-0.74	7	7
actin cytoskeleton organization	0.065	0.067	-10000	0	-0.6	3	3
GRB2	0.01	0.002	-10000	0	-10000	0	0
IL2	0.007	0.005	-10000	0	-10000	0	0
PIK3CA	0.013	0.001	-10000	0	-10000	0	0
Rac1/GTP	0.029	0.005	-10000	0	-10000	0	0
LCK	0.011	0.033	-10000	0	-0.74	1	1
BCL2	0.074	0.056	-10000	0	-0.53	1	1

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.004	0.026	-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	-0.003	0.07	-10000	0	-10000	0	0
IL27/IL27R/JAK1	-0.028	0.097	-10000	0	-10000	0	0
TBX21	-0.028	0.22	-10000	0	-0.62	43	43
IL12B	0.009	0.004	-10000	0	-10000	0	0
IL12A	0.001	0.072	-10000	0	-0.56	8	8
IL6ST	-0.018	0.14	-10000	0	-0.74	18	18
IL27RA/JAK1	-0.003	0.013	-10000	0	-10000	0	0
IL27	0.008	0.007	-10000	0	-10000	0	0
TYK2	0.011	0.003	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.06	0.14	-10000	0	-0.7	3	3
T-helper 2 cell differentiation	-0.003	0.07	-10000	0	-10000	0	0
T cell proliferation during immune response	-0.003	0.07	-10000	0	-10000	0	0
MAPKKK cascade	0.003	0.07	-10000	0	-10000	0	0
STAT3	0	0	-10000	0	-10000	0	0
STAT2	0	0	-10000	0	-10000	0	0
STAT1	0.001	0.003	-10000	0	-10000	0	0
IL12RB1	-0.038	0.18	-10000	0	-0.74	32	32
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.019	0.19	-10000	0	-0.63	13	13
IL27/IL27R/JAK2/TYK2	0.002	0.071	-10000	0	-10000	0	0
positive regulation of T cell mediated cytotoxicity	0.003	0.07	-10000	0	-10000	0	0
STAT1 (dimer)	-0.058	0.16	0.51	4	-0.75	7	11
JAK2	0.006	0.006	-10000	0	-10000	0	0
JAK1	0.001	0.003	-10000	0	-10000	0	0
STAT2 (dimer)	0.004	0.066	-10000	0	-10000	0	0
T cell proliferation	-0.049	0.18	-10000	0	-0.59	14	14
IL12/IL12R/TYK2/JAK2	0.008	0.092	-10000	0	-0.59	2	2
IL17A	-0.06	0.14	-10000	0	-0.7	3	3
mast cell activation	-0.003	0.07	-10000	0	-10000	0	0
IFNG	0.006	0.02	-10000	0	-0.13	4	4
T cell differentiation	-0.003	0.005	-10000	0	-0.023	3	3
STAT3 (dimer)	0.004	0.066	-10000	0	-10000	0	0
STAT5A (dimer)	0.004	0.066	-10000	0	-10000	0	0
STAT4 (dimer)	-0.003	0.087	-10000	0	-0.5	4	4
STAT4	-0.012	0.092	-10000	0	-0.74	8	8
T cell activation	-0.007	0.003	-10000	0	-10000	0	0
IL27R/JAK2/TYK2	-0.019	0.08	-10000	0	-10000	0	0
GATA3	-0.033	0.24	-10000	0	-1.4	14	14
IL18	0.007	0.044	-10000	0	-0.56	3	3
positive regulation of mast cell cytokine production	-0.012	0.058	-10000	0	-10000	0	0
IL27/EBI3	-0.002	0.041	-10000	0	-0.52	3	3
IL27RA	0.007	0.017	-10000	0	-10000	0	0
IL6	-0.12	0.28	-10000	0	-0.74	82	82
STAT5A	0	0	-10000	0	-10000	0	0
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	0.001	0.006	-10000	0	-10000	0	0
IL1B	-0.003	0.084	-10000	0	-0.56	11	11
EBI3	0.001	0.054	-10000	0	-0.69	3	3
TNF	-0.005	0.09	-10000	0	-0.55	13	13

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0	0	-9999	-10000	0	0
PTK2	0	0	-9999	-10000	0	0
CRKL	0.008	0.076	-9999	-0.38	18	18
GRB2/SOS1/SHC	0	0	-9999	-10000	0	0
HRAS	0	0	-9999	-10000	0	0
IRS1/Crk	-0.014	0.072	-9999	-0.38	18	18
IGF-1R heterotetramer/IGF1/PTP1B	-0.017	0.084	-9999	-0.45	18	18
AKT1	0.028	0.067	-9999	-10000	0	0
BAD	0.034	0.064	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.008	0.076	-9999	-0.38	18	18
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.014	0.072	-9999	-0.39	18	18
RAF1	0.037	0.061	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.013	0.068	-9999	-10000	0	0
YWHAZ	0	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.016	0.079	-9999	-0.42	18	18
PIK3CA	0	0	-9999	-10000	0	0
RPS6KB1	0.028	0.067	-9999	-10000	0	0
GNB2L1	0	0	-9999	-10000	0	0
positive regulation of MAPKKK cascade	0.032	0.054	-9999	-10000	0	0
PXN	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
cell adhesion	0	0	-9999	-10000	0	0
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.012	0.06	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.013	0.066	-9999	-10000	0	0
IGF-1R heterotetramer	0.007	0.017	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.014	0.072	-9999	-0.39	18	18
Crk/p130 Cas/Paxillin	-0.013	0.064	-9999	-10000	0	0
IGF1R	0.007	0.017	-9999	-10000	0	0
IGF1	-0.018	0.14	-9999	-0.74	19	19
IRS2/Crk	-0.016	0.074	-9999	-0.4	3	3
PI3K	-0.013	0.067	-9999	-10000	0	0
apoptosis	0.009	0.047	-9999	-10000	0	0
HRAS/GDP	0	0	-9999	-10000	0	0
PRKCD	0.019	0.092	-9999	-0.46	18	18
RAF1/14-3-3 E	0.04	0.055	-9999	-10000	0	0
BAD/14-3-3	0.038	0.06	-9999	-10000	0	0
PRKCZ	0.028	0.067	-9999	-10000	0	0
Crk/p130 Cas/Paxillin/FAK1	-0.01	0.049	-9999	-10000	0	0
PTPN1	0	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.018	0.091	-9999	-0.49	18	18
BCAR1	0	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.014	0.073	-9999	-0.39	18	18
mol:GDP	0	0	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
IRS1/NCK2	-0.014	0.072	-9999	-0.38	18	18
GRB10	0	0	-9999	-10000	0	0
PTPN11	0.008	0.076	-9999	-0.38	18	18
IRS1	0.001	0.082	-9999	-0.42	18	18
IRS2	0.006	0.084	-9999	-0.39	21	21
IGF-1R heterotetramer/IGF1	-0.021	0.11	-9999	-0.56	19	19
GRB2	0	0	-9999	-10000	0	0
PDPK1	-0.012	0.063	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
PRKD1	0.006	0.13	-9999	-0.48	30	30
SHC1	0	0	-9999	-10000	0	0

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.044	0.12	-9999	-10000	0	0
TC10/GTP	-0.042	0.12	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	0	0	-9999	-10000	0	0
HRAS	0	0	-9999	-10000	0	0
APS homodimer	0	0	-9999	-10000	0	0
GRB14	-0.044	0.17	-9999	-0.73	30	30
FOXO3	-0.003	0.014	-9999	-10000	0	0
AKT1	-0.02	0.078	-9999	-10000	0	0
INSR	0.011	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0	0	-9999	-10000	0	0
SORBS1	-0.085	0.24	-9999	-0.74	58	58
CRK	0	0	-9999	-10000	0	0
PTPN1	0.032	0	-9999	-10000	0	0
CAV1	-0.098	0.2	-9999	-0.42	137	137
CBL/APS/CAP/Crk-II/C3G	-0.046	0.13	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/NCK2	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0	0	-9999	-10000	0	0
RPS6KB1	0.03	0.084	-9999	-10000	0	0
PARD6A	-0.001	0.033	-9999	-0.74	1	1
CBL	0	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.017	0.069	-9999	-10000	0	0
HRAS/GTP	-0.001	0.015	-9999	-10000	0	0
Insulin Receptor	0.011	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0	0	-9999	-10000	0	0
PRKCI	-0.005	0.021	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.021	0.085	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
NCK2	0	0	-9999	-10000	0	0
RHOQ	0	0	-9999	-10000	0	0
mol:H2O2	0	0	-9999	-10000	0	0
HRAS/GDP	0	0	-9999	-10000	0	0
AKT2	-0.02	0.078	-9999	-10000	0	0
PRKCZ	-0.005	0.021	-9999	-10000	0	0
SH2B2	0	0	-9999	-10000	0	0
SHC/SHIP	-0.001	0.018	-9999	-10000	0	0
F2RL2	-0.1	0.22	-9999	-0.58	91	91
TRIP10	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	0	0	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0	0	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	-0.05	0.14	-9999	-0.43	58	58
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0	0	-9999	-10000	0	0
INPP5D	0.023	0.02	-9999	-0.42	1	1
SOS1	0	0	-9999	-10000	0	0
SGK1	-0.002	0.006	-9999	-10000	0	0
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
IRS1	0	0	-9999	-10000	0	0
p62DOK/RasGAP	0	0	-9999	-10000	0	0
INS	0.003	0	-9999	-10000	0	0
mol:PI-3-4-P2	0.023	0.02	-9999	-0.42	1	1
GRB2	0	0	-9999	-10000	0	0
EIF4EBP1	0.015	0.1	-9999	-10000	0	0
PTPRA	0.011	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS3	0	0	-9999	-10000	0	0
Par3/Par6	-0.054	0.12	-9999	-0.48	4	4

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.018	0.003	-9999	-10000	0	0
RAS family/GTP	-0.008	0.045	-9999	-0.33	1	1
NFATC4	0.031	0.056	-9999	-10000	0	0
ERBB2IP	0.002	0.004	-9999	-10000	0	0
HSP90 (dimer)	0	0	-9999	-10000	0	0
mammary gland morphogenesis	-0.011	0.061	-9999	-10000	0	0
JUN	0.043	0.059	-9999	-0.49	1	1
HRAS	0	0	-9999	-10000	0	0
DOCK7	0.028	0.067	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.014	0.073	-9999	-0.41	15	15
AKT1	0.01	0.002	-9999	-10000	0	0
BAD	0.018	0.001	-9999	-10000	0	0
MAPK10	-0.009	0.045	-9999	-0.35	3	3
mol:GTP	0	0.001	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.012	0.066	-9999	-10000	0	0
RAF1	0.047	0.059	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 2	-0.048	0.14	-9999	-0.44	53	53
STAT3	0	0	-9999	-10000	0	0
cell migration	0.04	0.046	-9999	-0.3	2	2
mol:PI-3-4-5-P3	0	0.001	-9999	-10000	0	0
cell proliferation	0.036	0.15	-9999	-0.56	8	8
FOS	0.005	0.2	-9999	-0.5	66	66
NRAS	0	0	-9999	-10000	0	0
mol:Ca2+	-0.011	0.061	-9999	-10000	0	0
MAPK3	0.044	0.11	-9999	-0.47	5	5
MAPK1	0.044	0.11	-9999	-0.47	5	5
JAK2	0.028	0.067	-9999	-10000	0	0
NF2	-0.001	0.018	-9999	-0.4	1	1
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0.013	0.062	-9999	-0.33	15	15
NRG1	-0.013	0.13	-9999	-0.74	15	15
GRB2/SOS1	0	0	-9999	-10000	0	0
MAPK8	0.031	0.062	-9999	-10000	0	0
MAPK9	-0.005	0.029	-9999	-10000	0	0
ERBB2	-0.002	0.027	-9999	-0.43	2	2
ERBB3	0.009	0.004	-9999	-10000	0	0
SHC1	0.008	0.004	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
apoptosis	0.003	0.008	-9999	-10000	0	0
STAT3 (dimer)	0	0	-9999	-10000	0	0
RNF41	0.025	0.005	-9999	-10000	0	0
FRAP1	0.009	0.002	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.008	0.041	-9999	-10000	0	0
ErbB2/ErbB2/HSP90 (dimer)	-0.001	0.022	-9999	-0.36	2	2
CHRNA1	0.041	0.12	-9999	-0.63	6	6
myelination	0.036	0.054	-9999	-10000	0	0
PPP3CB	0.026	0.063	-9999	-10000	0	0
KRAS	0	0	-9999	-10000	0	0
RAC1-CDC42/GDP	-0.009	0.048	-9999	-10000	0	0
NRG2	-0.078	0.23	-9999	-0.74	53	53
mol:GDP	0.014	0.062	-9999	-0.33	15	15
SOS1	0.008	0.004	-9999	-10000	0	0
MAP2K2	0.054	0.06	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
mol:cAMP	0	0.001	-9999	-10000	0	0
PTPN11	0.026	0.067	-9999	-10000	0	0
MAP2K1	0.034	0.11	-9999	-0.48	5	5
heart morphogenesis	-0.011	0.061	-9999	-10000	0	0
RAS family/GDP	-0.008	0.046	-9999	-10000	0	0
GRB2	0.008	0.004	-9999	-10000	0	0
PRKACA	-0.001	0.005	-9999	-10000	0	0
CHRNE	0.02	0.018	-9999	-0.24	1	1
HSP90AA1	0	0	-9999	-10000	0	0
activation of caspase activity	-0.01	0.002	-9999	-10000	0	0
nervous system development	-0.011	0.061	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	-0.005	0.047	-9999	-0.43	6	6
HDAC3	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC4	-0.05	0.16	-9999	-0.56	45	45
GATA1/HDAC5	-0.05	0.16	-9999	-0.56	45	45
GATA2/HDAC5	-0.061	0.17	-9999	-0.56	55	55
HDAC5/BCL6/BCoR	0	0	-9999	-10000	0	0
HDAC9	-0.005	0.055	-9999	-0.62	4	4
Glucocorticoid receptor/Hsp90/HDAC6	0	0	-9999	-10000	0	0
HDAC4/ANKRA2	0	0	-9999	-10000	0	0
HDAC5/YWHAB	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0	0	-9999	-10000	0	0
GATA2	-0.081	0.23	-9999	-0.74	55	55
HDAC4/RFXANK	0	0	-9999	-10000	0	0
BCOR	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0	0	-9999	-10000	0	0
HDAC5	0	0	-9999	-10000	0	0
GNB1/GNG2	-0.007	0.06	-9999	-0.56	6	6
Histones	-0.001	0.014	-9999	-10000	0	0
ADRBK1	0	0	-9999	-10000	0	0
HDAC4	0	0	-9999	-10000	0	0
XPO1	0	0	-9999	-10000	0	0
HDAC5/ANKRA2	0	0	-9999	-10000	0	0
HDAC4/Ubc9	0	0	-9999	-10000	0	0
HDAC7	0	0	-9999	-10000	0	0
HDAC5/14-3-3 E	0	0	-9999	-10000	0	0
TUBA1B	0	0	-9999	-10000	0	0
HDAC6	0	0	-9999	-10000	0	0
HDAC5/RFXANK	0	0	-9999	-10000	0	0
CAMK4	-0.004	0.057	-9999	-0.74	3	3
Tubulin/HDAC6	0	0	-9999	-10000	0	0
SUMO1	0	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0	0	-9999	-10000	0	0
GATA1	-0.066	0.21	-9999	-0.74	45	45
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
NR3C1	0	0	-9999	-10000	0	0
SUMO1/HDAC4	0	0	-9999	-10000	0	0
SRF	0	0	-9999	-10000	0	0
HDAC4/YWHAB	0	0	-9999	-10000	0	0
Tubulin	0	0	-9999	-10000	0	0
HDAC4/14-3-3 E	0	0	-9999	-10000	0	0
GNB1	-0.001	0.033	-9999	-0.74	1	1
RANGAP1	0	0	-9999	-10000	0	0
BCL6/BCoR	0	0	-9999	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	-0.001	0.021	-9999	-0.48	1	1
HDAC4/SRF	-0.003	0.037	-9999	-0.48	3	3
HDAC4/ER alpha	-0.027	0.12	-9999	-0.56	24	24
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.001	0.013	-9999	-10000	0	0
cell motility	0	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0	0	-9999	-10000	0	0
HDAC7/HDAC3	0	0	-9999	-10000	0	0
BCL6	0	0	-9999	-10000	0	0
HDAC4/CaMK II delta B	0	0	-9999	-10000	0	0
Hsp90/HDAC6	0	0	-9999	-10000	0	0
ESR1	-0.035	0.16	-9999	-0.74	24	24
HDAC6/HDAC11	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
MEF2C	-0.019	0.12	-9999	-0.74	13	13
RAN	0	0	-9999	-10000	0	0
HDAC4/MEF2C	-0.011	0.066	-9999	-0.4	14	14
GNG2	-0.007	0.073	-9999	-0.74	5	5
NCOR2	-0.001	0.033	-9999	-0.74	1	1
TUBB2A	0	0	-9999	-10000	0	0
HDAC11	0	0	-9999	-10000	0	0
HSP90AA1	0	0	-9999	-10000	0	0
RANBP2	0	0	-9999	-10000	0	0
ANKRA2	0	0	-9999	-10000	0	0
RFXANK	0	0	-9999	-10000	0	0
nuclear import	0	0	-9999	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0	0	-9999	-10000	0	0
ITGB7	-0.001	0.033	-9999	-0.74	1	1
ITGA4	-0.009	0.08	-9999	-0.74	6	6
alpha4/beta7 Integrin	-0.008	0.065	-9999	-0.56	7	7
alpha4/beta1 Integrin	-0.007	0.06	-9999	-0.56	6	6

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0	0	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.006	0.034	-10000	0	-10000	0	0
IRAK/TOLLIP	0	0	-10000	0	-10000	0	0
IKBKB	-0.001	0.026	-10000	0	-0.57	1	1
IKBKG	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.061	0.16	-10000	0	-0.47	65	65
IL1A	-0.051	0.18	-10000	0	-0.65	39	39
IL1B	0.005	0.092	-10000	0	-0.56	13	13
IRAK/TRAF6/p62/Atypical PKCs	0	0	-10000	0	-10000	0	0
IL1R2	-0.033	0.13	-10000	0	-0.57	29	29
IL1R1	-0.001	0.033	-10000	0	-0.74	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.001	0.041	0.22	9	-10000	0	9
TOLLIP	0	0	-10000	0	-10000	0	0
TICAM2	-0.009	0.08	-10000	0	-0.74	6	6
MAP3K3	0	0	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0	0	-10000	0	-10000	0	0
IKK complex/ELKS	0	0.004	-10000	0	-10000	0	0
JUN	0.042	0.012	-10000	0	-10000	0	0
MAP3K7	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.011	0.062	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.029	0.1	-10000	0	-0.45	18	18
PIK3R1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.027	0.097	-10000	0	-0.81	1	1
IL1 beta fragment/IL1R1/IL1RAP	-0.012	0.071	-10000	0	-0.43	14	14
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	0.037	0.013	-10000	0	-10000	0	0
IRAK1	0.022	0.004	-10000	0	-10000	0	0
IL1RN/IL1R1	-0.004	0.055	-10000	0	-0.66	3	3
IRAK4	0	0	-10000	0	-10000	0	0
PRKCI	0	0	-10000	0	-10000	0	0
TRAF6	0	0	-10000	0	-10000	0	0
PI3K	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.007	0.039	-10000	0	-10000	0	0
CHUK	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.012	0.071	-10000	0	-0.43	14	14
IL1 beta/IL1R2	-0.032	0.11	-10000	0	-0.5	13	13
IRAK/TRAF6/TAK1/TAB1/TAB2	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.009	0.056	-10000	0	-10000	0	0
IRAK3	-0.019	0.12	-10000	0	-0.74	13	13
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.015	0.078	-10000	0	-0.78	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.018	0.067	-10000	0	-0.62	1	1
IL1 alpha/IL1R1/IL1RAP	-0.032	0.12	-10000	0	-0.5	18	18
RELA	0	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0	0	-10000	0	-10000	0	0
MYD88	0	0	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0	0	-10000	0	-10000	0	0
IL1RAP	0	0	-10000	0	-10000	0	0
UBE2N	0	0	-10000	0	-10000	0	0
IRAK/TRAF6	-0.012	0.064	-10000	0	-0.63	1	1
CASP1	-0.003	0.046	-10000	0	-0.74	2	2
IL1RN/IL1R2	-0.027	0.1	-10000	0	-0.42	32	32
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.011	0.066	-10000	0	-10000	0	0
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.013	0.052	-10000	0	-0.61	1	1
PIK3CA	0	0	-10000	0	-10000	0	0
IL1RN	-0.004	0.053	-10000	0	-0.68	3	3
TRAF6/TAK1/TAB1/TAB2	0	0	-10000	0	-10000	0	0
MAP2K6	-0.001	0.012	-10000	0	-10000	0	0

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	-0.001	0.033	-10000	0	-0.74	1	1
EPHB2	-0.001	0.073	-10000	0	-0.57	8	8
EFNB1	0.018	0.027	-10000	0	-0.41	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.038	0.094	-10000	0	-0.43	3	3
Ephrin B2/EPHB1-2	-0.045	0.11	-10000	0	-0.43	5	5
neuron projection morphogenesis	-0.036	0.09	-10000	0	-0.41	3	3
Ephrin B1/EPHB1-2/Tiam1	-0.041	0.1	-10000	0	-0.47	3	3
DNM1	-0.002	0.036	-10000	0	-0.57	2	2
cell-cell signaling	0	0.001	-10000	0	-10000	0	0
MAP2K4	0.016	0.059	-10000	0	-0.72	3	3
YES1	-0.005	0.074	-10000	0	-0.95	3	3
Ephrin B1/EPHB1-2/NCK2	-0.041	0.1	-10000	0	-0.5	2	2
PI3K	-0.005	0.057	-10000	0	-0.73	3	3
mol:GDP	-0.041	0.1	-10000	0	-0.46	3	3
ITGA2B	-0.022	0.13	-10000	0	-0.74	15	15
endothelial cell proliferation	-0.001	0.022	-10000	0	-0.48	1	1
FYN	-0.005	0.074	-10000	0	-0.95	3	3
MAP3K7	-0.005	0.06	-10000	0	-0.77	3	3
FGR	-0.018	0.089	-10000	0	-0.99	3	3
TIAM1	-0.001	0.033	-10000	0	-0.74	1	1
PIK3R1	0	0	-10000	0	-10000	0	0
RGS3	0	0	-10000	0	-10000	0	0
cell adhesion	-0.023	0.098	-10000	0	-0.66	3	3
LYN	-0.006	0.075	-10000	0	-0.95	3	3
Ephrin B1/EPHB1-2/Src Family Kinases	-0.005	0.07	-10000	0	-0.9	3	3
Ephrin B1/EPHB1-2	-0.008	0.065	-10000	0	-0.83	3	3
SRC	-0.005	0.073	-10000	0	-0.94	3	3
ITGB3	-0.016	0.11	-10000	0	-0.74	11	11
EPHB1	-0.071	0.19	-10000	0	-0.58	62	62
EPHB4	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	-0.001	0.022	-10000	0	-0.48	1	1
alphaIIb/beta3 Integrin	-0.029	0.12	-10000	0	-0.56	26	26
BLK	-0.012	0.08	-10000	0	-0.95	3	3
HCK	-0.008	0.076	-10000	0	-0.95	3	3
regulation of stress fiber formation	0.04	0.1	0.49	2	-10000	0	2
MAPK8	0.023	0.056	-10000	0	-0.68	3	3
Ephrin B1/EPHB1-2/RGS3	-0.041	0.1	-10000	0	-0.5	2	2
endothelial cell migration	-0.004	0.056	-10000	0	-0.6	4	4
NCK2	0	0	-10000	0	-10000	0	0
PTPN13	-0.001	0.067	-10000	0	-0.85	3	3
regulation of focal adhesion formation	0.04	0.1	0.49	2	-10000	0	2
chemotaxis	0.04	0.1	0.49	2	-10000	0	2
PIK3CA	0	0	-10000	0	-10000	0	0
Rac1/GTP	-0.037	0.092	-10000	0	-0.42	3	3
angiogenesis	-0.008	0.064	-10000	0	-0.82	3	3
LCK	-0.006	0.077	-10000	0	-0.99	3	3

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0	0	-10000	0	-10000	0	0
NFATC1	0.046	0.019	-10000	0	-10000	0	0
NFATC2	0.002	0.069	-10000	0	-0.22	15	15
NFATC3	0	0	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.013	0.12	-10000	0	-0.5	20	20
Exportin 1/Ran/NUP214	0	0	-10000	0	-10000	0	0
mol:DAG	-0.001	0.002	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.035	0.1	-10000	0	-0.48	19	19
BCL2/BAX	-0.001	0.019	-10000	0	-0.42	1	1
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.001	0.004	-10000	0	-10000	0	0
CaM/Ca2+	-0.001	0.004	-10000	0	-10000	0	0
BAX	0	0	-10000	0	-10000	0	0
MAPK14	0.009	0.003	-10000	0	-10000	0	0
BAD	0	0	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.016	0.11	-10000	0	-0.51	17	17
Calcineurin A alpha-beta B1/BCL2	-0.001	0.026	-10000	0	-0.57	1	1
FKBP8	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.015	0.11	0.5	17	-10000	0	17
KPNB1	0	0	-10000	0	-10000	0	0
KPNA2	0	0	-10000	0	-10000	0	0
XPO1	0	0	-10000	0	-10000	0	0
SFN	-0.057	0.17	-10000	0	-0.58	49	49
MAP3K8	0.006	0.047	-10000	0	-0.74	2	2
NFAT4/CK1 alpha	0	0	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.053	0.12	-10000	0	-0.45	14	14
CABIN1	-0.014	0.12	-10000	0	-0.51	20	20
CALM1	0.009	0.003	-10000	0	-10000	0	0
RAN	0	0	-10000	0	-10000	0	0
MAP3K1	0	0	-10000	0	-10000	0	0
CAMK4	-0.004	0.057	-10000	0	-0.74	3	3
mol:Ca2+	-0.001	0.006	-10000	0	-10000	0	0
MAPK3	0	0	-10000	0	-10000	0	0
YWHAH	0	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.002	0.035	-10000	0	-0.56	2	2
YWHAB	0	0	-10000	0	-10000	0	0
MAPK8	0.009	0.003	-10000	0	-10000	0	0
MAPK9	0	0	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
FKBP1A	0	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	-0.003	0.017	-10000	0	-10000	0	0
PRKCH	0	0	-10000	0	-10000	0	0
CABIN1/Cbp/p300	-0.001	0.004	-10000	0	-10000	0	0
CASP3	0.009	0.003	-10000	0	-10000	0	0
PIM1	0	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0	-10000	0	-10000	0	0
apoptosis	0	0.007	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	-0.008	0.024	-10000	0	-10000	0	0
PRKCB	-0.04	0.17	-10000	0	-0.74	27	27
PRKCE	-0.001	0.033	-10000	0	-0.74	1	1
JNK2/NFAT4	0	0	-10000	0	-10000	0	0
BAD/BCL-XL	0	0	-10000	0	-10000	0	0
PRKCD	0	0	-10000	0	-10000	0	0
NUP214	0	0	-10000	0	-10000	0	0
PRKCZ	0.009	0.003	-10000	0	-10000	0	0
PRKCA	-0.003	0.046	-10000	0	-0.74	2	2
PRKCG	-0.041	0.15	-10000	0	-0.57	36	36
PRKCQ	-0.069	0.22	-10000	0	-0.74	47	47
FKBP38/BCL2	-0.001	0.019	-10000	0	-0.42	1	1
EP300	0	0.001	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0	0	-10000	0	-10000	0	0
NFATc/JNK1	0.046	0.024	-10000	0	-10000	0	0
CaM/Ca2+/FKBP38	0	0	-10000	0	-10000	0	0
FKBP12/FK506	0	0	-10000	0	-10000	0	0
CSNK1A1	0.015	0.008	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.003	0.038	-10000	0	-0.49	3	3
NFATc/ERK1	0.05	0.018	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.035	0.1	-10000	0	-0.48	19	19
NR4A1	-0.049	0.25	-10000	0	-0.68	65	65
GSK3B	0.009	0.003	-10000	0	-10000	0	0
positive T cell selection	0.018	0.007	-10000	0	-10000	0	0
NFAT1/CK1 alpha	-0.021	0.045	-10000	0	-10000	0	0
RCH1/ KPNB1	0	0	-10000	0	-10000	0	0
YWHAQ	0	0	-10000	0	-10000	0	0
PRKACA	0.009	0.003	-10000	0	-10000	0	0
AKAP5	-0.003	0.046	-10000	0	-0.74	2	2
MEF2D	0	0.001	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.046	0.024	-10000	0	-10000	0	0
CREBBP	0	0.001	-10000	0	-10000	0	0
BCL2	-0.001	0.026	-10000	0	-0.57	1	1

×

EPHB forward 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
Ephrin A5/EPHB2	-0.009	0.058	-10000	0	-0.39	11	11
cell-cell adhesion	0.033	0.08	0.47	1	-10000	0	1
Ephrin B/EPHB2/RasGAP	-0.006	0.043	-10000	0	-0.4	1	1
ITSN1	0	0	-10000	0	-10000	0	0
PIK3CA	0	0	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.013	0.066	-10000	0	-0.35	18	18
Ephrin B1/EPHB1	-0.044	0.12	-10000	0	-0.36	62	62
HRAS/GDP	-0.032	0.081	-10000	0	-0.39	1	1
Ephrin B/EPHB1/GRB7	-0.039	0.099	-10000	0	-0.4	2	2
Endophilin/SYNJ1	-0.006	0.041	-10000	0	-0.38	1	1
KRAS	0	0	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.037	0.097	-10000	0	-0.4	2	2
endothelial cell migration	-0.001	0.018	-10000	0	-0.4	1	1
GRB2	0	0	-10000	0	-10000	0	0
GRB7	-0.005	0.051	-10000	0	-0.57	4	4
PAK1	-0.011	0.058	-10000	0	-10000	0	0
HRAS	0	0	-10000	0	-10000	0	0
RRAS	-0.006	0.041	-10000	0	-0.38	1	1
DNM1	-0.002	0.036	-10000	0	-0.57	2	2
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.035	0.092	-10000	0	-0.38	2	2
lamellipodium assembly	-0.033	0.08	-10000	0	-0.47	1	1
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.019	0.049	-10000	0	-10000	0	0
PIK3R1	0	0	-10000	0	-10000	0	0
EPHB2	-0.009	0.072	-10000	0	-0.57	8	8
EPHB3	-0.021	0.11	-10000	0	-0.57	18	18
EPHB1	-0.072	0.19	-10000	0	-0.58	62	62
EPHB4	0	0	-10000	0	-10000	0	0
mol:GDP	-0.023	0.081	-10000	0	-0.43	1	1
Ephrin B/EPHB2	-0.007	0.044	-10000	0	-0.41	1	1
Ephrin B/EPHB3	-0.012	0.059	-10000	0	-0.41	1	1
JNK cascade	-0.009	0.11	-10000	0	-0.48	2	2
Ephrin B/EPHB1	-0.038	0.099	-10000	0	-0.41	2	2
RAP1/GDP	-0.019	0.07	-10000	0	-10000	0	0
EFNB2	-0.001	0.033	-10000	0	-0.74	1	1
EFNB3	-0.002	0.036	-10000	0	-0.57	2	2
EFNB1	0	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.045	0.11	-10000	0	-0.5	3	3
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
CDC42/GTP	-0.033	0.081	-10000	0	-0.46	1	1
Rap1/GTP	-0.032	0.079	-10000	0	-0.47	1	1
axon guidance	-0.009	0.057	-10000	0	-0.39	11	11
MAPK3	0.025	0.055	-10000	0	-10000	0	0
MAPK1	0.025	0.055	-10000	0	-10000	0	0
Rac1/GDP	-0.02	0.074	-10000	0	-0.39	1	1
actin cytoskeleton reorganization	-0.027	0.067	-10000	0	-0.38	1	1
CDC42/GDP	-0.02	0.074	-10000	0	-0.39	1	1
PI3K	-0.001	0.018	-10000	0	-0.41	1	1
EFNA5	-0.004	0.057	-10000	0	-0.74	3	3
Ephrin B2/EPHB4	-0.001	0.022	-10000	0	-0.48	1	1
Ephrin B/EPHB2/Intersectin/N-WASP	-0.003	0.024	-10000	0	-0.3	1	1
CDC42	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.031	0.078	-10000	0	-0.46	1	1
PTK2	0.01	0.026	-10000	0	-10000	0	0
MAP4K4	-0.009	0.11	-10000	0	-0.49	2	2
SRC	0	0	-10000	0	-10000	0	0
KALRN	-0.009	0.08	-10000	0	-0.74	6	6
Intersectin/N-WASP	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.026	0.064	-10000	0	-0.48	1	1
MAP2K1	0.019	0.057	-10000	0	-10000	0	0
WASL	0	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.043	0.11	-10000	0	-0.52	2	2
cell migration	0.027	0.058	-10000	0	-10000	0	0
NRAS	0	0	-10000	0	-10000	0	0
SYNJ1	-0.006	0.041	-10000	0	-0.38	1	1
PXN	0	0	-10000	0	-10000	0	0
TF	0.01	0.092	-10000	0	-10000	0	0
HRAS/GTP	-0.035	0.087	-10000	0	-0.5	1	1
Ephrin B1/EPHB1-2	-0.044	0.11	-10000	0	-0.32	69	69
cell adhesion mediated by integrin	-0.002	0.041	0.41	1	-10000	0	1
RAC1	0	0	-10000	0	-10000	0	0
mol:GTP	-0.038	0.093	-10000	0	-0.54	1	1
RAC1-CDC42/GTP	-0.04	0.087	-10000	0	-0.47	2	2
RASA1	0	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.019	0.07	-10000	0	-10000	0	0
ruffle organization	-0.032	0.08	-10000	0	-0.47	1	1
NCK1	0	0	-10000	0	-10000	0	0
receptor internalization	0.032	0.048	-10000	0	-10000	0	0
Ephrin B/EPHB2/KALRN	-0.011	0.061	-10000	0	-0.4	7	7
ROCK1	0.01	0.063	-10000	0	-0.31	18	18
RAS family/GDP	-0.023	0.058	-10000	0	-10000	0	0
Rac1/GTP	-0.034	0.084	-10000	0	-0.5	1	1
Ephrin B/EPHB1/Src/Paxillin	-0.019	0.05	-10000	0	-0.3	2	2

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.001	0.031	0.28	2	-10000	0	2
DAPP1	0.007	0.12	-10000	0	-0.58	15	15
Src family/SYK family/BLNK-LAT/BTK-ITK	0.002	0.17	-10000	0	-0.65	24	24
mol:DAG	0.025	0.089	0.2	1	-0.27	24	25
HRAS	0.01	0.002	-10000	0	-10000	0	0
RAP1A	0	0.001	-10000	0	-10000	0	0
ARF5/GDP	0.026	0.057	-10000	0	-0.31	8	8
PLCG2	0	0	-10000	0	-10000	0	0
PLCG1	0	0	-10000	0	-10000	0	0
ARF5	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.032	0.25	2	-0.35	3	5
ARF1/GTP	-0.001	0.031	0.26	2	-10000	0	2
RHOA	0	0	-10000	0	-10000	0	0
YES1	0	0	-10000	0	-10000	0	0
RAP1A/GTP	-0.001	0.031	0.24	2	-0.35	3	5
ADAP1	-0.007	0.056	0.25	2	-0.38	8	10
ARAP3	-0.001	0.032	0.25	2	-0.35	3	5
INPPL1	0	0	-10000	0	-10000	0	0
PREX1	-0.012	0.092	-10000	0	-0.74	8	8
ARHGEF6	-0.028	0.14	-10000	0	-0.74	19	19
ARHGEF7	0	0	-10000	0	-10000	0	0
ARF1	0	0	-10000	0	-10000	0	0
NRAS	0.01	0.002	-10000	0	-10000	0	0
FYN	-0.001	0.033	-10000	0	-0.74	1	1
ARF6	0	0	-10000	0	-10000	0	0
FGR	-0.054	0.19	-10000	0	-0.74	37	37
mol:Ca2+	0.023	0.048	-10000	0	-10000	0	0
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	-0.001	0.033	-10000	0	-0.74	1	1
ZAP70	-0.012	0.092	-10000	0	-0.74	8	8
mol:IP3	0.026	0.066	-10000	0	-0.23	1	1
LYN	-0.003	0.046	-10000	0	-0.74	2	2
ARF1/GDP	0.026	0.057	-10000	0	-0.31	8	8
RhoA/GDP	-0.005	0.038	0.26	2	-10000	0	2
PDK1/Src/Hsp90	0	0	-10000	0	-10000	0	0
BLNK	-0.001	0.033	-10000	0	-0.74	1	1
actin cytoskeleton reorganization	0.046	0.068	-10000	0	-0.49	3	3
SRC	0	0	-10000	0	-10000	0	0
PLEKHA2	0.026	0.022	-10000	0	-0.48	1	1
RAC1	0	0	-10000	0	-10000	0	0
PTEN	-0.003	0.045	-10000	0	-0.71	2	2
HSP90AA1	0	0	-10000	0	-10000	0	0
ARF6/GTP	-0.001	0.031	0.28	2	-10000	0	2
RhoA/GTP	-0.001	0.03	0.24	2	-10000	0	2
Src family/SYK family/BLNK-LAT	-0.034	0.11	-10000	0	-0.52	18	18
BLK	-0.036	0.15	-10000	0	-0.66	27	27
PDPK1	0	0	-10000	0	-10000	0	0
CYTH1	-0.001	0.03	-10000	0	-10000	0	0
HCK	-0.009	0.08	-10000	0	-0.74	6	6
CYTH3	-0.001	0.03	0.25	2	-10000	0	2
CYTH2	-0.001	0.03	0.25	2	-10000	0	2
KRAS	0.01	0.002	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0	0.018	-10000	0	-10000	0	0
SGK1	0	0.02	-10000	0	-10000	0	0
INPP5D	-0.001	0.033	-10000	0	-0.74	1	1
mol:GDP	0.022	0.06	-10000	0	-0.33	8	8
SOS1	0	0	-10000	0	-10000	0	0
SYK	-0.001	0.033	-10000	0	-0.74	1	1
ARF6/GDP	-0.005	0.038	0.27	2	-10000	0	2
mol:PI-3-4-5-P3	-0.001	0.035	0.34	2	-0.35	3	5
ARAP3/RAP1A/GTP	-0.001	0.031	0.24	2	-0.35	3	5
VAV1	-0.007	0.073	-10000	0	-0.74	5	5
mol:PI-3-4-P2	0.019	0.026	-10000	0	-0.56	1	1
RAS family/GTP/PI3K Class I	-0.002	0.027	-10000	0	-0.35	3	3
PLEKHA1	0.026	0.022	-10000	0	-0.48	1	1
Rac1/GDP	0.026	0.057	-10000	0	-0.31	8	8
LAT	0	0	-10000	0	-10000	0	0
Rac1/GTP	-0.02	0.1	-10000	0	-0.46	21	21
ITK	-0.029	0.1	-10000	0	-10000	0	0
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.023	0.12	0.22	1	-0.4	24	25
LCK	-0.001	0.033	-10000	0	-0.74	1	1
BTK	-0.038	0.11	-10000	0	-10000	0	0

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.006	0.066	-10000	0	-0.74	4	4
CLTC	0.027	0.009	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.023	0.008	-10000	0	-10000	0	0
Dynamin 2/GTP	-0.001	0.014	-10000	0	-0.32	1	1
EXOC4	0	0	-10000	0	-10000	0	0
CD59	0.025	0.007	-10000	0	-10000	0	0
CPE	0.014	0.028	-10000	0	-0.42	2	2
CTNNB1	0	0	-10000	0	-10000	0	0
membrane fusion	-0.001	0.007	-10000	0	-10000	0	0
CTNND1	0.028	0.014	-10000	0	-10000	0	0
DNM2	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.028	0.006	-10000	0	-10000	0	0
TSHR	0.005	0.063	-10000	0	-0.36	15	15
INS	0.01	0.002	-10000	0	-10000	0	0
BIN1	-0.003	0.046	-10000	0	-0.74	2	2
mol:Choline	-0.001	0.007	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.015	0.016	-10000	0	-0.35	1	1
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.001	0.014	-10000	0	-0.31	1	1
JUP	0.025	0.007	-10000	0	-10000	0	0
ASAP2/amphiphysin II	-0.002	0.028	-10000	0	-0.44	2	2
ARF6/GTP	0	0	-10000	0	-10000	0	0
CDH1	0.025	0.007	-10000	0	-10000	0	0
clathrin-independent pinocytosis	0	0	-10000	0	-10000	0	0
MAPK8IP3	0	0	-10000	0	-10000	0	0
positive regulation of endocytosis	0	0	-10000	0	-10000	0	0
EXOC2	0	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0	0	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0	0.01	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.016	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0	0	-10000	0	-10000	0	0
ACAP1	-0.001	0.007	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	-0.039	0.12	-10000	0	-0.36	3	3
clathrin heavy chain/ACAP1	0.032	0.01	-10000	0	-10000	0	0
JIP4/KLC1	0	0	-10000	0	-10000	0	0
EXOC1	0	0	-10000	0	-10000	0	0
exocyst	0	0	-10000	0	-10000	0	0
RALA/GTP	0	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0	0	-10000	0	-10000	0	0
receptor recycling	0	0	-10000	0	-10000	0	0
CTNNA1	0.028	0.014	-10000	0	-10000	0	0
NME1	0.015	0.017	-10000	0	-0.36	1	1
clathrin coat assembly	0.027	0.009	-10000	0	-10000	0	0
IL2RA	0.022	0.025	-10000	0	-10000	0	0
VAMP3	0.016	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.003	0.032	-10000	0	-0.35	4	4
EXOC6	0	0	-10000	0	-10000	0	0
PLD1	-0.001	0.01	-10000	0	-10000	0	0
PLD2	0	0	-10000	0	-10000	0	0
EXOC5	0	0	-10000	0	-10000	0	0
PIP5K1C	0.028	0.006	-10000	0	-10000	0	0
SDC1	0.024	0.014	-10000	0	-10000	0	0
ARF6/GDP	-0.001	0.016	-10000	0	-0.35	1	1
EXOC7	0	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	0	0.01	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.001	0.007	-10000	0	-10000	0	0
endocytosis	0.002	0.027	0.44	2	-10000	0	2
SCAMP2	0	0	-10000	0	-10000	0	0
ADRB2	-0.085	0.19	-10000	0	-0.38	143	143
EXOC3	0	0	-10000	0	-10000	0	0
ASAP2	0	0	-10000	0	-10000	0	0
Dynamin 2/GDP	-0.001	0.014	-10000	0	-0.31	1	1
KLC1	0	0	-10000	0	-10000	0	0
AVPR2	-0.065	0.18	-10000	0	-0.38	118	118
RALA	0	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0	0.009	-10000	0	-10000	0	0

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.092	0.19	-9999	-0.77	5	5
RAD9A	0	0	-9999	-10000	0	0
AP1	-0.068	0.18	-9999	-0.56	61	61
IFNAR2	0.007	0.006	-9999	-10000	0	0
AKT1	-0.005	0.064	-9999	-0.3	11	11
ER alpha/Oestrogen	-0.027	0.12	-9999	-0.57	24	24
NFX1/SIN3/HDAC complex	0.025	0.021	-9999	-10000	0	0
EGF	-0.008	0.098	-9999	-0.69	10	10
SMG5	0	0	-9999	-10000	0	0
SMG6	0	0	-9999	-10000	0	0
SP3/HDAC2	0	0.001	-9999	-10000	0	0
TERT/c-Abl	-0.12	0.15	-9999	-0.72	5	5
SAP18	0.006	0.005	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	-0.025	0.13	-9999	-0.58	27	27
WRN	-0.001	0.033	-9999	-0.74	1	1
SP1	0.008	0.006	-9999	-10000	0	0
SP3	0.007	0.005	-9999	-10000	0	0
TERF2IP	0	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.1	0.14	-9999	-0.64	5	5
Mad/Max	0	0	-9999	-10000	0	0
TERT	-0.094	0.2	-9999	-0.79	5	5
CCND1	-0.085	0.22	-9999	-1.3	6	6
MAX	0.007	0.005	-9999	-10000	0	0
RBBP7	0.006	0.005	-9999	-10000	0	0
RBBP4	0.006	0.005	-9999	-10000	0	0
TERF2	0	0	-9999	-10000	0	0
PTGES3	0	0	-9999	-10000	0	0
SIN3A	0.006	0.005	-9999	-10000	0	0
Telomerase/911	0.016	0.032	-9999	-10000	0	0
CDKN1B	0.015	0.051	-9999	-0.46	4	4
RAD1	0	0	-9999	-10000	0	0
XRCC5	0	0	-9999	-10000	0	0
XRCC6	0	0	-9999	-10000	0	0
SAP30	0.006	0.005	-9999	-10000	0	0
TRF2/PARP2	0	0	-9999	-10000	0	0
UBE3A	0.006	0.005	-9999	-10000	0	0
JUN	0.006	0.005	-9999	-10000	0	0
E6	-0.003	0.004	-9999	-10000	0	0
HPV-16 E6/E6AP	0	0.001	-9999	-10000	0	0
FOS	-0.084	0.24	-9999	-0.74	61	61
IFN-gamma/IRF1	-0.006	0.055	-9999	-0.5	6	6
PARP2	0	0	-9999	-10000	0	0
BLM	-0.011	0.08	-9999	-0.57	10	10
Telomerase	-0.028	0.055	-9999	-10000	0	0
IRF1	0.009	0.007	-9999	-10000	0	0
ESR1	-0.03	0.16	-9999	-0.74	24	24
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0	0	-9999	-10000	0	0
HDAC1	0.006	0.005	-9999	-10000	0	0
HDAC2	0.007	0.006	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.023	0.005	-9999	-10000	0	0
ABL1	0	0	-9999	-10000	0	0
MXD1	0.007	0.005	-9999	-10000	0	0
MRE11A	0	0	-9999	-10000	0	0
HUS1	0	0	-9999	-10000	0	0
RPS6KB1	0	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.12	0.15	-9999	-0.72	5	5
NR2F2	0.01	0.012	-9999	-10000	0	0
MAPK3	0.01	0.009	-9999	-10000	0	0
MAPK1	0.01	0.009	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.005	0.007	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
HNRNPC	0	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0	0	-9999	-10000	0	0
NBN	0	0	-9999	-10000	0	0
EGFR	-0.017	0.12	-9999	-0.63	18	18
mol:Oestrogen	-0.002	0.003	-9999	-10000	0	0
EGF/EGFR	-0.027	0.12	-9999	-0.5	27	27
MYC	0.007	0.005	-9999	-10000	0	0
IL2	0	0.012	-9999	-10000	0	0
KU	0	0	-9999	-10000	0	0
RAD50	0	0	-9999	-10000	0	0
HSP90AA1	0	0	-9999	-10000	0	0
TGFB1	0.005	0.007	-9999	-10000	0	0
TRF2/BLM	-0.008	0.054	-9999	-0.38	10	10
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.12	0.15	-9999	-0.71	5	5
SP1/HDAC2	0	0.002	-9999	-10000	0	0
PINX1	0	0	-9999	-10000	0	0
Telomerase/EST1A	-0.1	0.14	-9999	-0.64	5	5
Smad3/Myc	0.011	0.015	-9999	-10000	0	0
911 complex	0	0	-9999	-10000	0	0
IFNG	0.001	0.076	-9999	-0.68	6	6
Telomerase/PinX1	-0.1	0.14	-9999	-0.64	5	5
Telomerase/AKT1/mTOR/p70S6K	-0.003	0.063	-9999	-10000	0	0
SIN3B	0.006	0.005	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
Telomerase/EST1B	-0.1	0.14	-9999	-0.64	5	5
response to DNA damage stimulus	0.003	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0	0	-9999	-10000	0	0
TRF2/WRN	-0.001	0.023	-9999	-0.52	1	1
Telomerase/hnRNP C1/C2	-0.1	0.14	-9999	-0.64	5	5
E2F1	0.007	0.006	-9999	-10000	0	0
ZNFX1	0.006	0.005	-9999	-10000	0	0
PIF1	-0.059	0.17	-9999	-0.57	51	51
NCL	0	0	-9999	-10000	0	0
DKC1	0	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0	0	-9999	-10000	0	0
TRAF2/ASK1	0	0	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
MAP2K3	0.027	0.024	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.034	0.022	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
GADD45G	-0.009	0.08	-9999	-0.74	6	6
TXN	0.007	0	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
GADD45A	0	0	-9999	-10000	0	0
GADD45B	-0.019	0.12	-9999	-0.74	13	13
MAP3K1	0	0	-9999	-10000	0	0
MAP3K6	0	0	-9999	-10000	0	0
MAP3K7	0	0	-9999	-10000	0	0
MAP3K4	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
ASK1/ASK2	0	0	-9999	-10000	0	0
TAK1/TAB family	0	0	-9999	-10000	0	0
RAC1/OSM/MEKK3	0	0	-9999	-10000	0	0
TRAF2	0	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.002	0.005	-9999	-10000	0	0
TRAF6	0.007	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
CAMK2B	-0.069	0.19	-9999	-0.57	60	60
CCM2	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.042	0.12	-9999	-0.35	60	60
MAPK11	0	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.038	0.1	-9999	-0.32	60	60
OSM/MEKK3	0	0	-9999	-10000	0	0
TAOK1	0.014	0.019	-9999	-0.42	1	1
TAOK2	0.015	0	-9999	-10000	0	0
TAOK3	0.015	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
MAP3K5	0	0	-9999	-10000	0	0
MAP3K10	-0.001	0.026	-9999	-0.57	1	1
MAP3K3	0	0	-9999	-10000	0	0
TRX/ASK1	0	0	-9999	-10000	0	0
GADD45/MTK1/MTK1	-0.015	0.082	-9999	-0.43	18	18

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.005	0.041	-9999	-0.4	2	2
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
CRKL	0	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	-0.004	0.033	-9999	-10000	0	0
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.002	0.022	-9999	-0.48	1	1
antigen processing and presentation of peptide antigen via MHC class I	-0.013	0.044	-9999	-10000	0	0
CaM/Ca2+	-0.004	0.038	-9999	-10000	0	0
RAP1A	0	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.004	0.039	-9999	-10000	0	0
AKT1	-0.004	0.034	-9999	-10000	0	0
MAP2K1	0.042	0.044	-9999	-10000	0	0
MAP3K11	0.034	0.045	-9999	-10000	0	0
IFNGR1	0.009	0.034	-9999	-0.74	1	1
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.051	0.13	-9999	-0.48	39	39
Rap1/GTP	-0.003	0.028	-9999	-10000	0	0
CRKL/C3G	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.005	0.043	-9999	-0.41	1	1
CEBPB	0.039	0.13	-9999	-0.72	2	2
STAT3	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.007	0.066	-9999	-1.2	1	1
STAT1	-0.004	0.038	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
IFN-gamma (dimer)	0.002	0.075	-9999	-0.68	6	6
PIK3CA	0	0	-9999	-10000	0	0
STAT1 (dimer)/PIAS1	-0.004	0.036	-9999	-10000	0	0
CEBPB/PTGES2/Cbp/p300	-0.02	0.068	-9999	-0.41	2	2
mol:Ca2+	-0.005	0.041	-9999	-0.4	2	2
MAPK3	0.042	0.064	-9999	-10000	0	0
STAT1 (dimer)	-0.016	0.058	-9999	-10000	0	0
MAPK1	0.042	0.064	-9999	-10000	0	0
JAK2	0.01	0.005	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
JAK1	0.01	0.005	-9999	-10000	0	0
CAMK2D	0	0	-9999	-10000	0	0
DAPK1	0.016	0.19	-9999	-0.64	38	38
SMAD7	0.038	0.042	-9999	-10000	0	0
CBL/CRKL/C3G	-0.004	0.034	-9999	-10000	0	0
PI3K	-0.004	0.036	-9999	-10000	0	0
IFNG	0.002	0.076	-9999	-0.68	6	6
apoptosis	0.015	0.13	-9999	-0.44	38	38
CAMK2G	0	0	-9999	-10000	0	0
STAT3 (dimer)	0	0	-9999	-10000	0	0
CAMK2A	-0.057	0.2	-9999	-0.74	39	39
CAMK2B	-0.069	0.19	-9999	-0.57	60	60
FRAP1	0.044	0.038	-9999	-10000	0	0
PRKCD	-0.004	0.034	-9999	-10000	0	0
RAP1B	0	0	-9999	-10000	0	0
negative regulation of cell growth	-0.013	0.044	-9999	-10000	0	0
PTPN2	0	0	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
IRF1	0.065	0.037	-9999	-10000	0	0
STAT1 (dimer)/PIASy	-0.004	0.037	-9999	-10000	0	0
SOCS1	-0.002	0.065	-9999	-1.5	1	1
mol:GDP	-0.004	0.033	-9999	-10000	0	0
CASP1	0.037	0.047	-9999	-0.33	2	2
PTGES2	0	0	-9999	-10000	0	0
IRF9	0.043	0.043	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.004	0.036	-9999	-10000	0	0
RAP1/GDP	-0.003	0.029	-9999	-10000	0	0
CBL	0.033	0.044	-9999	-10000	0	0
MAP3K1	0.034	0.045	-9999	-0.4	1	1
PIAS1	0	0	-9999	-10000	0	0
PIAS4	0	0.001	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.013	0.044	-9999	-10000	0	0
PTPN11	0.027	0.045	-9999	-0.4	2	2
CREBBP	0	0	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	-0.011	0.069	-9999	-0.44	12	12
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.009	0.059	-9999	-0.38	12	12
SUMO1	0	0	-9999	-10000	0	0
ZFPM1	-0.001	0.033	-9999	-0.74	1	1
NPC/RanGAP1/SUMO1/Ubc9	0	0	-9999	-10000	0	0
FKBP3	0	0	-9999	-10000	0	0
Histones	-0.005	0.03	-9999	-10000	0	0
YY1/LSF	-0.001	0.013	-9999	-10000	0	0
SMG5	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	-0.008	0.052	-9999	-0.34	12	12
I kappa B alpha/HDAC1	-0.006	0.035	-9999	-10000	0	0
SAP18	0	0	-9999	-10000	0	0
RELA	-0.007	0.046	-9999	-0.3	12	12
HDAC1/Smad7	0	0	-9999	-10000	0	0
RANGAP1	0	0	-9999	-10000	0	0
HDAC3/TR2	-0.006	0.035	-9999	-10000	0	0
NuRD/MBD3 Complex	0	0.009	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.007	0.041	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.081	0.23	-9999	-0.74	55	55
GATA1	-0.066	0.21	-9999	-0.74	45	45
Mad/Max	0	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	-0.019	0.062	-9999	-0.45	1	1
RBBP7	0	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
RBBP4	0	0	-9999	-10000	0	0
MAX	0	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
NFKBIA	-0.007	0.04	-9999	-10000	0	0
KAT2B	-0.001	0.033	-9999	-0.74	1	1
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0	0	-9999	-10000	0	0
SIN3 complex	0	0	-9999	-10000	0	0
SMURF1	0	0	-9999	-10000	0	0
CHD3	0	0	-9999	-10000	0	0
SAP30	0	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0	0	-9999	-10000	0	0
YY1/HDAC3	-0.005	0.033	-9999	-10000	0	0
YY1/HDAC2	-0.001	0.013	-9999	-10000	0	0
YY1/HDAC1	-0.001	0.013	-9999	-10000	0	0
NuRD/MBD2 Complex (MeCP1)	0	0	-9999	-10000	0	0
PPARG	-0.05	0.13	-9999	-0.45	12	12
HDAC8/hEST1B	0	0	-9999	-10000	0	0
UBE2I	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
TNFRSF1A	0	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	-0.007	0.04	-9999	-0.43	1	1
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
CREBBP	0	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0	0.009	-9999	-10000	0	0
HDAC1	0	0	-9999	-10000	0	0
HDAC3	-0.007	0.04	-9999	-10000	0	0
HDAC2	0	0	-9999	-10000	0	0
YY1	0.025	0.016	-9999	-0.34	1	1
HDAC8	0	0	-9999	-10000	0	0
SMAD7	0	0	-9999	-10000	0	0
NCOR2	-0.001	0.033	-9999	-0.74	1	1
MXD1	0	0	-9999	-10000	0	0
STAT3	0.022	0	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0	0	-9999	-10000	0	0
YY1/LSF/HDAC1	-0.001	0.011	-9999	-10000	0	0
YY1/SAP30/HDAC1	-0.001	0.011	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.022	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.007	0.04	-9999	-10000	0	0
histone deacetylation	0.041	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	-0.005	0.031	-9999	-10000	0	0
nuclear export	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GATAD2B	0	0	-9999	-10000	0	0
GATAD2A	0	0	-9999	-10000	0	0
GATA2/HDAC3	-0.053	0.14	-9999	-0.44	55	55
GATA1/HDAC1	-0.05	0.16	-9999	-0.56	45	45
GATA1/HDAC3	-0.044	0.13	-9999	-0.44	45	45
CHD4	0	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.014	0.087	-9999	-0.55	13	13
SIN3/HDAC complex/Mad/Max	0	0	-9999	-10000	0	0
NuRD Complex	0	0.009	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.005	0.029	-9999	-10000	0	0
SIN3B	0	0	-9999	-10000	0	0
MTA2	0	0	-9999	-10000	0	0
SIN3A	0	0	-9999	-10000	0	0
XPO1	0	0	-9999	-10000	0	0
SUMO1/HDAC1	0	0	-9999	-10000	0	0
HDAC complex	0	0	-9999	-10000	0	0
GATA1/Fog1	-0.051	0.16	-9999	-0.56	46	46
FKBP25/HDAC1/HDAC2	0	0	-9999	-10000	0	0
TNF	-0.019	0.12	-9999	-0.72	13	13
negative regulation of cell growth	0.041	0	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.01	0.062	-9999	-0.4	12	12
SIN3/HDAC complex/NCoR1	0	0	-9999	-10000	0	0
TFCP2	0	0	-9999	-10000	0	0
NR2C1	0	0	-9999	-10000	0	0
MBD3	-0.001	0.033	-9999	-0.74	1	1
MBD2	0	0	-9999	-10000	0	0

×

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

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	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	-0.001	0.026	-9999	-0.57	1	1
Caspase 8 (4 units)	-0.011	0.048	-9999	-10000	0	0
NEF	-0.007	0.037	-9999	-10000	0	0
NFKBIA	-0.001	0.012	-9999	-10000	0	0
BIRC3	0.03	0.086	-9999	-0.75	6	6
CYCS	0.032	0.065	-9999	-10000	0	0
RIPK1	0	0	-9999	-10000	0	0
CD247	-0.025	0.13	-9999	-0.82	12	12
MAP2K7	0.034	0.051	-9999	-10000	0	0
protein ubiquitination	0.057	0.038	-9999	-10000	0	0
CRADD	0	0	-9999	-10000	0	0
DAXX	0	0	-9999	-10000	0	0
FAS	-0.003	0.046	-9999	-0.74	2	2
BID	0.026	0.068	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha	-0.004	0.035	-9999	-10000	0	0
TRADD	0	0	-9999	-10000	0	0
MAP3K5	0	0	-9999	-10000	0	0
CFLAR	0	0	-9999	-10000	0	0
FADD	0	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.004	0.035	-9999	-10000	0	0
MAPK8	0.04	0.049	-9999	-10000	0	0
APAF1	0	0	-9999	-10000	0	0
TRAF1	0	0	-9999	-10000	0	0
TRAF2	0	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.015	0.062	-9999	-0.3	16	16
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	-0.006	0.034	-9999	-10000	0	0
CHUK	0.058	0.04	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.002	0.025	-9999	-0.4	2	2
TCRz/NEF	-0.027	0.12	-9999	-0.51	27	27
TNF	-0.019	0.12	-9999	-0.72	13	13
FASLG	-0.02	0.2	-9999	-0.8	27	27
NFKB1	-0.001	0.012	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.013	0.076	-9999	-0.46	14	14
CASP6	-0.007	0.029	-9999	-10000	0	0
CASP7	0.061	0.084	-9999	-0.6	6	6
RELA	-0.001	0.012	-9999	-10000	0	0
CASP2	0	0	-9999	-10000	0	0
CASP3	0.061	0.084	-9999	-0.6	6	6
TNFRSF1A	0	0	-9999	-10000	0	0
TNFR1A/BAG4	-0.001	0.019	-9999	-0.42	1	1
CASP8	0	0	-9999	-10000	0	0
CASP9	0	0	-9999	-10000	0	0
MAP3K14	0.054	0.042	-9999	-10000	0	0
APAF-1/Caspase 9	-0.013	0.061	-9999	-0.48	6	6
BCL2	0.045	0.048	-9999	-10000	0	0

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.01	0.084	-10000	0	-0.71	7	7
HRAS	0	0	-10000	0	-10000	0	0
EGFR	-0.023	0.12	-10000	0	-0.63	18	18
AKT	0.031	0.035	-10000	0	-0.38	3	3
FOXO3	0	0	-10000	0	-10000	0	0
AKT1	0	0	-10000	0	-10000	0	0
FOXO1	0	0	-10000	0	-10000	0	0
AKT3	-0.004	0.057	-10000	0	-0.74	3	3
FOXO4	0	0	-10000	0	-10000	0	0
MET	-0.004	0.053	-10000	0	-0.68	3	3
PIK3CA	0	0	-10000	0	-10000	0	0
PIK3CB	0	0	-10000	0	-10000	0	0
NRAS	0	0	-10000	0	-10000	0	0
PIK3CG	-0.065	0.21	-10000	0	-0.74	44	44
PIK3R3	-0.001	0.033	-10000	0	-0.74	1	1
PIK3R2	0	0	-10000	0	-10000	0	0
NF1	0	0	-10000	0	-10000	0	0
RAS	0.015	0.036	-10000	0	-10000	0	0
ERBB2	-0.002	0.036	-10000	0	-0.57	2	2
proliferation/survival/translation	-0.019	0.036	0.22	2	-10000	0	2
PI3K	0.014	0.053	-10000	0	-0.25	5	5
PIK3R1	0	0	-10000	0	-10000	0	0
KRAS	0	0	-10000	0	-10000	0	0
FOXO	0.038	0.015	-10000	0	-10000	0	0
AKT2	0	0	-10000	0	-10000	0	0
PTEN	-0.003	0.046	-10000	0	-0.74	2	2

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP1	0	0	-9999	-10000	0	0
mol:DAG	0.017	0.076	-9999	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	0	0	-9999	-10000	0	0
CaM/Ca2+	-0.015	0.062	-9999	-10000	0	0
HIF1A	0	0	-9999	-10000	0	0
GAB1	0	0	-9999	-10000	0	0
AKT1	-0.011	0.047	-9999	-10000	0	0
PLCG1	0.017	0.076	-9999	-10000	0	0
NOS3	0.039	0.072	-9999	-0.58	1	1
CBL	0	0	-9999	-10000	0	0
mol:NO	0.039	0.07	-9999	-0.55	1	1
FLT1	0.026	0	-9999	-10000	0	0
PGF	-0.031	0.13	-9999	-0.57	27	27
VEGFR1 homodimer/NRP2/VEGFR121	-0.003	0.038	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
eNOS/Hsp90	0.043	0.068	-9999	-0.53	1	1
endothelial cell proliferation	0.016	0.096	-9999	-0.61	1	1
mol:Ca2+	0.017	0.075	-9999	-10000	0	0
MAPK3	0.029	0.072	-9999	-10000	0	0
MAPK1	0.029	0.072	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
PLGF homodimer	-0.031	0.13	-9999	-0.57	27	27
PRKACA	0	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.2	0.33	-9999	-0.74	137	137
VEGFA homodimer	0	0	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.035	0.07	-9999	-10000	0	0
PI3K	-0.015	0.063	-9999	-10000	0	0
PRKCA	0.023	0.076	-9999	-10000	0	0
PRKCB	0.001	0.12	-9999	-10000	0	0
VEGFR1 homodimer/PLGF homodimer	-0.018	0.077	-9999	-10000	0	0
VEGFA	0	0	-9999	-10000	0	0
VEGFB	0	0	-9999	-10000	0	0
mol:IP3	0.017	0.076	-9999	-10000	0	0
RASA1	0.035	0	-9999	-10000	0	0
NRP2	-0.006	0.066	-9999	-0.74	4	4
VEGFR1 homodimer	0.026	0	-9999	-10000	0	0
VEGFB homodimer	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.064	0.18	-9999	-0.59	7	7
PTPN11	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.015	0.062	-9999	-10000	0	0
mol:L-citrulline	0.039	0.07	-9999	-0.55	1	1
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0	0	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	0	0	-9999	-10000	0	0
CD2AP	0	0	-9999	-10000	0	0
PI3K/GAB1	-0.014	0.058	-9999	-10000	0	0
PDPK1	-0.014	0.057	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/SHP2	0	0	-9999	-10000	0	0
mol:NADP	0.039	0.07	-9999	-0.55	1	1
HSP90AA1	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP2	-0.004	0.042	-9999	-0.47	4	4

×

Circadian rhythm 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	-0.001	0.012	-9999	-10000	0	0
CLOCK	0.013	0	-9999	-10000	0	0
TIMELESS/CRY2	0	0	-9999	-10000	0	0
DEC1/BMAL1	-0.023	0.095	-9999	-0.41	28	28
ATR	0	0	-9999	-10000	0	0
NR1D1	0.038	0	-9999	-10000	0	0
ARNTL	0.013	0	-9999	-10000	0	0
TIMELESS	0.038	0	-9999	-10000	0	0
NPAS2	0.013	0	-9999	-10000	0	0
CRY2	0	0	-9999	-10000	0	0
mol:CO	-0.012	0	-9999	-10000	0	0
CHEK1	-0.001	0.026	-9999	-0.57	1	1
mol:HEME	0.012	0	-9999	-10000	0	0
PER1	-0.003	0.046	-9999	-0.74	2	2
BMAL/CLOCK/NPAS2	0.035	0	-9999	-10000	0	0
BMAL1/CLOCK	0.037	0.038	-9999	-10000	0	0
S phase of mitotic cell cycle	-0.001	0.012	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	-0.001	0.012	-9999	-10000	0	0
mol:NADPH	0.012	0	-9999	-10000	0	0
PER1/TIMELESS	-0.002	0.026	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	-0.032	0.13	-9999	-0.57	28	28

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.019	0.026	-10000	0	-0.56	1	1
MAP4K4	0.033	0.056	-10000	0	-0.64	1	1
BAG4	-0.001	0.026	-10000	0	-0.57	1	1
PKC zeta/ceramide	-0.002	0.016	-10000	0	-10000	0	0
NFKBIA	0	0	-10000	0	-10000	0	0
BIRC3	-0.009	0.08	-10000	0	-0.74	6	6
BAX	0.001	0.008	-10000	0	-10000	0	0
RIPK1	0	0	-10000	0	-10000	0	0
AKT1	0.017	0.003	-10000	0	-10000	0	0
BAD	-0.001	0.016	0.19	1	-10000	0	1
SMPD1	0.02	0.041	-10000	0	-0.23	12	12
RB1	-0.002	0.025	-10000	0	-0.43	1	1
FADD/Caspase 8	0.041	0.053	-10000	0	-0.61	1	1
MAP2K4	0.005	0.015	-10000	0	-10000	0	0
NSMAF	0	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.005	0.015	-10000	0	-10000	0	0
EGF	-0.014	0.097	-10000	0	-0.69	10	10
mol:ceramide	-0.01	0.017	0.2	1	-10000	0	1
MADD	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.019	0.026	-10000	0	-0.56	1	1
ASAH1	0	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.002	0.025	0.19	1	-0.42	1	2
cell proliferation	-0.013	0.062	-10000	0	-0.33	17	17
BID	0.024	0.038	-10000	0	-0.38	1	1
MAP3K1	-0.001	0.016	0.19	1	-10000	0	1
EIF2A	0.012	0.015	-10000	0	-10000	0	0
TRADD	0	0	-10000	0	-10000	0	0
CRADD	0	0	-10000	0	-10000	0	0
MAPK3	0.015	0.015	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.015	0.015	-10000	0	-10000	0	0
Cathepsin D/ceramide	-0.002	0.016	0.17	1	-10000	0	1
FADD	0.033	0.056	-10000	0	-0.64	1	1
KSR1	-0.001	0.016	-10000	0	-10000	0	0
MAPK8	0.009	0.015	-10000	0	-10000	0	0
PRKRA	-0.001	0.016	0.19	1	-10000	0	1
PDGFA	-0.001	0.033	-10000	0	-0.74	1	1
TRAF2	0	0	-10000	0	-10000	0	0
IGF1	-0.028	0.14	-10000	0	-0.73	19	19
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.01	0.017	0.2	1	-10000	0	1
CTSD	0	0	-10000	0	-10000	0	0
regulation of nitric oxide biosynthetic process	0	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.014	0.066	-10000	0	-0.35	17	17
PRKCD	0	0	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.019	0.026	-10000	0	-0.56	1	1
RelA/NF kappa B1	0	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.009	0.052	-10000	0	-0.68	1	1
TNFR1A/BAG4/TNF-alpha	-0.013	0.076	-10000	0	-0.46	14	14
mol:Sphingosine-1-phosphate	0.019	0.026	-10000	0	-0.55	1	1
MAP2K1	0.012	0.015	-10000	0	-10000	0	0
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
CYCS	0.001	0.012	-10000	0	-10000	0	0
TNFRSF1A	0	0	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
TNFR1A/BAG4	-0.001	0.019	-10000	0	-0.42	1	1
EIF2AK2	0.005	0.015	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.012	0.074	-10000	0	-0.48	12	12
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	-0.005	0.027	-10000	0	-10000	0	0
MAP2K2	0.012	0.015	-10000	0	-10000	0	0
SMPD3	0.018	0.063	-10000	0	-0.42	6	6
TNF	-0.019	0.12	-10000	0	-0.72	13	13
PKC zeta/PAR4	0	0	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	-0.005	0.037	0.23	10	-10000	0	10
NF kappa B1/RelA/I kappa B alpha	0	0	-10000	0	-10000	0	0
AIFM1	0.001	0.012	0.14	1	-10000	0	1
BCL2	-0.001	0.026	-10000	0	-0.57	1	1

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.007	0.058	-9999	-0.49	7	7
CRKL	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0	0	-9999	-10000	0	0
ITGA4	-0.009	0.08	-9999	-0.74	6	6
alpha4/beta7 Integrin/MAdCAM1	-0.008	0.057	-9999	-0.43	7	7
EPO	-0.007	0.063	-9999	-0.57	6	6
alpha4/beta7 Integrin	-0.008	0.065	-9999	-0.56	7	7
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.007	0.06	-9999	-0.56	6	6
EPO/EPOR (dimer)	-0.005	0.045	-9999	-0.42	6	6
lamellipodium assembly	0.001	0.005	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
ARF6	0	0	-9999	-10000	0	0
JAK2	-0.006	0.041	-9999	-10000	0	0
PXN	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
MADCAM1	-0.005	0.051	-9999	-0.57	4	4
cell adhesion	-0.008	0.057	-9999	-0.43	7	7
CRKL/CBL	0	0	-9999	-10000	0	0
ITGB1	0	0	-9999	-10000	0	0
SRC	0.018	0.079	-9999	-0.53	8	8
ITGB7	-0.001	0.033	-9999	-0.74	1	1
RAC1	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.012	0.083	-9999	-0.5	12	12
p130Cas/Crk/Dock1	-0.009	0.063	-9999	-0.72	2	2
VCAM1	-0.01	0.083	-9999	-0.66	8	8
RHOA	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.005	0.047	-9999	-0.43	6	6
BCAR1	0.025	0.075	-9999	-0.5	8	8
EPOR	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
GIT1	0	0	-9999	-10000	0	0
Rac1/GTP	0.001	0.005	-9999	-10000	0	0

×

PDGFR-beta signaling 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	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.005	0.032	-9999	-0.62	1	1
PDGFB-D/PDGFRB/SLAP	-0.031	0.13	-9999	-0.58	27	27
PDGFB-D/PDGFRB/APS/CBL	-0.001	0.021	-9999	-0.48	1	1
AKT1	-0.005	0.042	-9999	-0.53	1	1
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.031	0.04	-9999	-0.66	1	1
PIK3CA	0	0	-9999	-10000	0	0
FGR	-0.044	0.16	-9999	-0.6	37	37
mol:Ca2+	0.027	0.041	-9999	-0.7	1	1
MYC	0.043	0.052	-9999	-0.46	1	1
SHC1	0	0	-9999	-10000	0	0
HRAS/GDP	-0.001	0.017	-9999	-10000	0	0
LRP1/PDGFRB/PDGFB	-0.001	0.021	-9999	-0.48	1	1
GRB10	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
GO:0007205	0.027	0.042	-9999	-0.71	1	1
PTEN	-0.003	0.046	-9999	-0.74	2	2
GRB2	0	0	-9999	-10000	0	0
GRB7	-0.005	0.051	-9999	-0.57	4	4
PDGFB-D/PDGFRB/SHP2	-0.001	0.025	-9999	-0.56	1	1
PDGFB-D/PDGFRB/GRB10	-0.001	0.025	-9999	-0.56	1	1
cell cycle arrest	-0.031	0.13	-9999	-0.58	27	27
HRAS	0	0	-9999	-10000	0	0
HIF1A	0.054	0.044	-9999	-0.46	1	1
GAB1	0.027	0.055	-9999	-0.72	1	1
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.032	0.051	-9999	-0.66	1	1
PDGFB-D/PDGFRB	0.002	0.024	-9999	-0.49	1	1
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	-0.001	0.025	-9999	-0.56	1	1
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.006	0.036	-9999	-0.62	1	1
positive regulation of MAPKKK cascade	-0.001	0.025	-9999	-0.56	1	1
PIK3R1	0	0	-9999	-10000	0	0
mol:IP3	0.027	0.042	-9999	-0.72	1	1
E5	0	0.001	-9999	-10000	0	0
CSK	0.001	0.003	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.004	0.045	-9999	-0.45	5	5
SHB	0	0	-9999	-10000	0	0
BLK	-0.021	0.1	-9999	-0.59	16	16
PTPN2	0.01	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	-0.001	0.025	-9999	-0.56	1	1
BCAR1	0	0	-9999	-10000	0	0
VAV2	0.028	0.069	-9999	-0.76	1	1
CBL	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	-0.003	0.043	-9999	-0.56	3	3
LCK	-0.002	0.035	-9999	-0.55	2	2
PDGFRB	0.009	0.034	-9999	-0.74	1	1
ACP1	0	0	-9999	-10000	0	0
HCK	-0.007	0.07	-9999	-0.59	7	7
ABL1	0.024	0.054	-9999	-0.65	1	1
PDGFB-D/PDGFRB/CBL	0.025	0.06	-9999	-0.77	1	1
PTPN1	0.01	0.001	-9999	-10000	0	0
SNX15	0	0	-9999	-10000	0	0
STAT3	0	0	-9999	-10000	0	0
STAT1	0	0	-9999	-10000	0	0
cell proliferation	0.042	0.05	-9999	-0.42	1	1
SLA	-0.04	0.17	-9999	-0.74	27	27
actin cytoskeleton reorganization	0.002	0.02	-9999	-10000	0	0
SRC	0	0.022	-9999	-0.49	1	1
PI3K	-0.006	0.046	-9999	-0.6	1	1
PDGFB-D/PDGFRB/GRB7/SHC	-0.004	0.037	-9999	-0.48	1	1
SH2B2	0	0	-9999	-10000	0	0
PLCgamma1/SPHK1	0.031	0.041	-9999	-0.69	1	1
LYN	-0.002	0.044	-9999	-0.56	3	3
LRP1	0	0	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
STAT5B	0	0	-9999	-10000	0	0
STAT5A	0	0	-9999	-10000	0	0
NCK1-2/p130 Cas	0	0.018	-9999	-10000	0	0
SPHK1	0.01	0.003	-9999	-10000	0	0
EDG1	0.001	0.001	-9999	-10000	0	0
mol:DAG	0.027	0.042	-9999	-0.72	1	1
PLCG1	0.027	0.043	-9999	-0.74	1	1
NHERF/PDGFRB	-0.007	0.057	-9999	-0.56	4	4
YES1	0	0.022	-9999	-0.48	1	1
cell migration	-0.006	0.057	-9999	-0.55	4	4
SHC/Grb2/SOS1	0	0.018	-9999	-10000	0	0
SLC9A3R2	-0.004	0.057	-9999	-0.74	3	3
SLC9A3R1	-0.005	0.051	-9999	-0.57	4	4
NHERF1-2/PDGFRB/PTEN	-0.008	0.059	-9999	-0.48	6	6
FYN	-0.001	0.034	-9999	-0.53	2	2
DOK1	0.029	0.021	-9999	-0.44	1	1
HRAS/GTP	0	0	-9999	-10000	0	0
PDGFB	0	0	-9999	-10000	0	0
RAC1	0.039	0.065	-9999	-0.66	1	1
PRKCD	0.029	0.021	-9999	-0.44	1	1
FER	0.029	0.021	-9999	-0.44	1	1
MAPKKK cascade	-0.001	0.017	-9999	-10000	0	0
RASA1	0.029	0.021	-9999	-0.44	1	1
NCK1	0	0	-9999	-10000	0	0
NCK2	0	0	-9999	-10000	0	0
p62DOK/Csk	0.002	0.02	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHB	-0.001	0.025	-9999	-0.56	1	1
chemotaxis	0.024	0.053	-9999	-0.63	1	1
STAT1-3-5/STAT1-3-5	-0.001	0.016	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	-0.001	0.025	-9999	-0.57	1	1
PTPRJ	-0.003	0.046	-9999	-0.74	2	2

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	0.003	0.046	0.73	2	-10000	0	2
PI3K Class IB/PDE3B	-0.003	0.046	-10000	0	-0.74	2	2
PDE3B	-0.003	0.046	-10000	0	-0.74	2	2

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.001	0.021	-10000	0	-10000	0	0
CaM/Ca2+	0	0	-10000	0	-10000	0	0
AKT1	0	0	-10000	0	-10000	0	0
AKT2	0	0	-10000	0	-10000	0	0
STXBP4	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.034	0.032	0.23	1	-10000	0	1
YWHAZ	0	0	-10000	0	-10000	0	0
CALM1	0	0	-10000	0	-10000	0	0
YWHAQ	0	0	-10000	0	-10000	0	0
TBC1D4	0.02	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0	0	-10000	0	-10000	0	0
YWHAB	0	0	-10000	0	-10000	0	0
SNARE/Synip	0	0	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
ASIP	-0.002	0.036	-10000	0	-0.57	2	2
PRKCI	0	0	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0	0	-10000	0	-10000	0	0
RHOQ	0	0	-10000	0	-10000	0	0
GYS1	0.028	0	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
TRIP10	0	0	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-10000	0	-10000	0	0
AS160/14-3-3	-0.009	0.029	-10000	0	-10000	0	0
VAMP2	0	0	-10000	0	-10000	0	0
SLC2A4	0.034	0.034	-10000	0	-10000	0	0
STX4	0	0	-10000	0	-10000	0	0
GSK3B	0.022	0	-10000	0	-10000	0	0
SFN	-0.057	0.17	-10000	0	-0.58	49	49
LNPEP	0	0	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
telencephalon oligodendrocyte cell migration	0.006	0.034	-9999	-10000	0	0
GNAI2	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.006	0.047	-9999	-0.37	8	8
mol:GDP	0	0	-9999	-10000	0	0
GNAO1	-0.004	0.049	-9999	-0.63	3	3
RhoA/GTP	-0.006	0.035	-9999	-10000	0	0
negative regulation of cAMP metabolic process	-0.007	0.04	-9999	-0.3	2	2
GNAZ	-0.009	0.08	-9999	-0.74	6	6
GNAI3	0	0	-9999	-10000	0	0
GNA12	0	0	-9999	-10000	0	0
S1PR5	-0.01	0.075	-9999	-0.6	8	8
mol:GTP	0	0	-9999	-10000	0	0
S1P/S1P5/Gi	-0.007	0.04	-9999	-0.31	2	2
RhoA/GDP	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
GNAI1	-0.001	0.033	-9999	-0.74	1	1

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.024	0.037	-9999	-10000	0	0
PLK1	-0.089	0.22	-9999	-0.73	3	3
CDKN1B	0.05	0.087	-9999	-10000	0	0
FOXO3	-0.023	0.16	-9999	-0.64	3	3
KAT2B	0.007	0.037	-9999	-0.75	1	1
FOXO1/SIRT1	0.018	0.026	-9999	-10000	0	0
CAT	-0.017	0.17	-9999	-1.4	2	2
CTNNB1	0	0	-9999	-10000	0	0
AKT1	0.009	0.016	-9999	-10000	0	0
FOXO1	0.027	0.022	-9999	-10000	0	0
MAPK10	0.023	0.056	-9999	-0.41	8	8
mol:GTP	0.002	0	-9999	-10000	0	0
FOXO4	0.08	0.032	-9999	-10000	0	0
response to oxidative stress	-0.003	0.02	-9999	-10000	0	0
FOXO3A/SIRT1	-0.064	0.1	-9999	-0.61	2	2
XPO1	0.01	0	-9999	-10000	0	0
EP300	0.006	0.006	-9999	-10000	0	0
BCL2L11	0.015	0.028	-9999	-10000	0	0
FOXO1/SKP2	-0.003	0.028	-9999	-10000	0	0
mol:GDP	-0.003	0.02	-9999	-10000	0	0
RAN	0.011	0	-9999	-10000	0	0
GADD45A	0.046	0.074	-9999	-10000	0	0
YWHAQ	0	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.054	0.031	-9999	-10000	0	0
MST1	0.007	0.029	-9999	-0.56	1	1
CSNK1D	0	0	-9999	-10000	0	0
CSNK1E	0	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.038	0.038	-9999	-10000	0	0
YWHAB	0	0	-9999	-10000	0	0
MAPK8	0.03	0.008	-9999	-10000	0	0
MAPK9	0.03	0.008	-9999	-10000	0	0
YWHAG	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
YWHAZ	0	0	-9999	-10000	0	0
SIRT1	0.008	0.013	-9999	-10000	0	0
SOD2	0.054	0.098	-9999	-10000	0	0
RBL2	0.018	0.11	-9999	-10000	0	0
RAL/GDP	0.014	0.015	-9999	-10000	0	0
CHUK	0.008	0.015	-9999	-10000	0	0
Ran/GTP	0	0	-9999	-10000	0	0
CSNK1G2	0	0	-9999	-10000	0	0
RAL/GTP	0.017	0.018	-9999	-10000	0	0
CSNK1G1	0	0	-9999	-10000	0	0
FASLG	-0.042	0.29	-9999	-1.5	20	20
SKP2	-0.003	0.044	-9999	-0.57	3	3
USP7	0.011	0	-9999	-10000	0	0
IKBKB	0.007	0.029	-9999	-0.56	1	1
CCNB1	-0.034	0.18	-9999	-0.73	3	3
FOXO1-3a-4/beta catenin	-0.015	0.04	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.003	0.028	-9999	-10000	0	0
CSNK1A1	0	0	-9999	-10000	0	0
SGK1	0.008	0.015	-9999	-10000	0	0
CSNK1G3	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
ZFAND5	0.081	0.028	-9999	-10000	0	0
SFN	-0.057	0.17	-9999	-0.58	49	49
CDK2	0.006	0.007	-9999	-10000	0	0
FOXO3A/14-3-3	0.02	0.053	-9999	-10000	0	0
CREBBP	0.006	0.007	-9999	-10000	0	0
FBXO32	-0.018	0.15	-9999	-0.7	1	1
BCL6	0.018	0.11	-9999	-10000	0	0
RALB	0.011	0	-9999	-10000	0	0
RALA	0.011	0	-9999	-10000	0	0
YWHAH	0	0	-9999	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	0.027	0	-9999	-10000	0	0
SNTA1	0	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.025	0.024	-9999	-0.35	2	2
MAPK12	0.027	0.015	-9999	-0.31	1	1
CCND1	0.014	0.051	-9999	-0.44	6	6
p38 gamma/SNTA1	-0.001	0.013	-9999	-10000	0	0
MAP2K3	0	0	-9999	-10000	0	0
PKN1	0	0	-9999	-10000	0	0
G2/M transition checkpoint	0.027	0.015	-9999	-0.3	1	1
MAP2K6	0.021	0.016	-9999	-0.34	1	1
MAPT	0.023	0.045	-9999	-0.37	6	6
MAPK13	0.02	0	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.015	0	-9999	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0	0	-9999	-10000	0	0
Rac1/GDP	0.001	0.007	-9999	-10000	0	0
DOCK1	0	0	-9999	-10000	0	0
ITGA4	-0.009	0.08	-9999	-0.74	6	6
RAC1	0	0	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.008	0.065	-9999	-0.56	7	7
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.006	0.052	-9999	-0.48	6	6
alpha4/beta7 Integrin/Paxillin	-0.006	0.051	-9999	-0.43	7	7
lamellipodium assembly	0.001	0.006	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
ARF6	0	0	-9999	-10000	0	0
TLN1	0	0	-9999	-10000	0	0
PXN	0.02	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
ARF6/GTP	-0.004	0.04	-9999	-10000	0	0
cell adhesion	-0.005	0.043	-9999	-10000	0	0
CRKL/CBL	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	-0.005	0.047	-9999	-0.43	6	6
ITGB1	0	0	-9999	-10000	0	0
ITGB7	-0.001	0.033	-9999	-0.74	1	1
ARF6/GDP	0.001	0.007	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.01	0.071	-9999	-0.81	2	2
p130Cas/Crk/Dock1	0	0	-9999	-10000	0	0
VCAM1	-0.01	0.083	-9999	-0.66	8	8
alpha4/beta1 Integrin/Paxillin/Talin	-0.005	0.044	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.005	0.044	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
mol:GDP	0.005	0.043	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GIT1	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.005	0.044	-9999	-10000	0	0
Rac1/GTP	0.001	0.006	-9999	-10000	0	0

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.007	0.061	-10000	0	-0.46	8	8
MAPK9	0.007	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	0.001	0.019	-10000	0	-0.42	1	1
GNB1/GNG2	-0.006	0.053	-10000	0	-0.48	6	6
GNB1	-0.001	0.033	-10000	0	-0.74	1	1
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.007	0	-10000	0	-10000	0	0
Gs family/GTP	-0.003	0.035	-10000	0	-0.45	3	3
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	0.001	0.008	0.11	3	-10000	0	3
GNAL	-0.004	0.057	-10000	0	-0.74	3	3
GNG2	-0.007	0.073	-10000	0	-0.74	5	5
CRH	-0.001	0.026	-10000	0	-0.57	1	1
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.007	0	-10000	0	-10000	0	0
MAPK11	0.007	0	-10000	0	-10000	0	0

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0	0	-9999	-10000	0	0
adherens junction organization	0.032	0.033	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
Rac1/GDP	-0.009	0.049	-9999	-10000	0	0
FMN1	0.012	0.1	-9999	-0.38	32	32
mol:IP3	0	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0	0	-9999	-10000	0	0
CTNNB1	0	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0	0	-9999	-10000	0	0
CTNND1	0.011	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.039	0	-9999	-10000	0	0
VASP	0.039	0	-9999	-10000	0	0
ZYX	0.039	0	-9999	-10000	0	0
JUB	0.039	0	-9999	-10000	0	0
EGFR(dimer)	-0.011	0.057	-9999	-0.38	6	6
E-cadherin/beta catenin-gamma catenin	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
PIK3CA	0.011	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
FYN	0.043	0.036	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
JUP	0	0	-9999	-10000	0	0
PIK3R1	0.011	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
CDH1	0	0	-9999	-10000	0	0
RhoA/GDP	-0.009	0.049	-9999	-10000	0	0
establishment of polarity of embryonic epithelium	0.039	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
EGFR	-0.023	0.12	-9999	-0.63	18	18
CASR	0.036	0.039	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
AKT2	0	0	-9999	-10000	0	0
actin cable formation	0.019	0.099	-9999	-10000	0	0
apoptosis	0	0	-9999	-10000	0	0
CTNNA1	0.011	0	-9999	-10000	0	0
mol:GDP	-0.01	0.053	-9999	-10000	0	0
PIP5K1A	0.039	0	-9999	-10000	0	0
PLCG1	0	0	-9999	-10000	0	0
Rac1/GTP	-0.01	0.052	-9999	-0.34	6	6
homophilic cell adhesion	0.001	0	-9999	-10000	0	0

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0	0	-9999	-10000	0	0
SMAD2	0.012	0.014	-9999	-0.29	1	1
SMAD3	0.036	0.013	-9999	-10000	0	0
SMAD3/SMAD4	0	0.003	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	0	0	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	0	0.01	-9999	-10000	0	0
PPM1A	0	0	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
SMAD2/SMAD4	-0.001	0.012	-9999	-10000	0	0
MAP3K1	0	0	-9999	-10000	0	0
TRAP-1/SMAD4	0	0	-9999	-10000	0	0
MAPK3	0	0	-9999	-10000	0	0
MAPK1	0	0	-9999	-10000	0	0
NUP214	0	0	-9999	-10000	0	0
CTDSP1	0	0	-9999	-10000	0	0
CTDSP2	0	0	-9999	-10000	0	0
CTDSPL	-0.001	0.033	-9999	-0.74	1	1
KPNB1	0	0	-9999	-10000	0	0
TGFBRAP1	0	0	-9999	-10000	0	0
UBE2I	0	0	-9999	-10000	0	0
NUP153	0	0	-9999	-10000	0	0
KPNA2	0	0	-9999	-10000	0	0
PIAS4	0	0	-9999	-10000	0	0

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.072	0.018	-9999	-10000	0	0
ERC1	0	0	-9999	-10000	0	0
RIP2/NOD2	-0.002	0.035	-9999	-0.56	2	2
NFKBIA	0.042	0	-9999	-10000	0	0
BIRC2	0	0	-9999	-10000	0	0
IKBKB	-0.001	0.026	-9999	-0.57	1	1
RIPK2	0	0	-9999	-10000	0	0
IKBKG	-0.001	0.015	-9999	-10000	0	0
IKK complex/A20	-0.01	0.055	-9999	-10000	0	0
NEMO/A20/RIP2	0	0	-9999	-10000	0	0
XPO1	0	0	-9999	-10000	0	0
NEMO/ATM	-0.001	0.014	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
Exportin 1/RanGTP	0	0	-9999	-10000	0	0
IKK complex/ELKS	-0.001	0.016	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0	0	-9999	-10000	0	0
NOD2	-0.003	0.046	-9999	-0.74	2	2
NFKB1	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
MALT1	0	0	-9999	-10000	0	0
cIAP1/UbcH5C	0	0	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
TNF/TNFR1A	-0.014	0.087	-9999	-0.55	13	13
TRAF6	0	0	-9999	-10000	0	0
PRKCA	-0.003	0.046	-9999	-0.74	2	2
CHUK	0	0	-9999	-10000	0	0
UBE2D3	0	0	-9999	-10000	0	0
TNF	-0.019	0.12	-9999	-0.72	13	13
NF kappa B1 p50/RelA	0	0	-9999	-10000	0	0
BCL10	0	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.041	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
TNFRSF1A	0	0	-9999	-10000	0	0
IKK complex	-0.001	0.017	-9999	-10000	0	0
CYLD	0	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.003	0.027	-9999	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0	0	-9999	-10000	0	0
PLK4	-0.001	0.026	-9999	-0.57	1	1
regulation of centriole replication	0.019	0.019	-9999	-0.42	1	1

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.038	0.004	-10000	0	-10000	0	0
regulation of axonogenesis	-0.024	0.019	-10000	0	-10000	0	0
myoblast fusion	0.002	0.015	-10000	0	-10000	0	0
mol:GTP	-0.001	0.006	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.002	0.025	0.39	2	-10000	0	2
ARF1/GTP	0	0.003	-10000	0	-10000	0	0
mol:GM1	0.009	0.005	-10000	0	-10000	0	0
mol:Choline	0.023	0.028	-10000	0	-0.33	3	3
lamellipodium assembly	-0.001	0.018	-10000	0	-10000	0	0
MAPK3	0.025	0.004	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.002	0.025	-10000	0	-0.39	2	2
ARF1	0	0	-10000	0	-10000	0	0
ARF6/GDP	-0.002	0.015	-10000	0	-10000	0	0
ARF1/GDP	-0.001	0.014	-10000	0	-10000	0	0
ARF6	0.008	0.003	-10000	0	-10000	0	0
RAB11A	0	0	-10000	0	-10000	0	0
TIAM1	0.01	0.033	-10000	0	-0.74	1	1
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.025	0.004	-10000	0	-10000	0	0
actin filament bundle formation	0.001	0.013	-10000	0	-10000	0	0
KALRN	-0.005	0.048	-10000	0	-0.44	6	6
RAB11FIP3/RAB11A	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.001	0.013	-10000	0	-10000	0	0
NME1	0.01	0.026	-10000	0	-0.57	1	1
Rac1/GDP	-0.001	0.013	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	-0.001	0.006	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	-0.001	0.018	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
liver development	-0.001	0.006	-10000	0	-10000	0	0
ARF6/GTP	-0.001	0.006	-10000	0	-10000	0	0
RhoA/GTP	0	0.003	-10000	0	-10000	0	0
mol:GDP	-0.001	0.016	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	0	0.001	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
PLD1	0.015	0.031	-10000	0	-0.38	3	3
RAB11FIP3	0	0	-10000	0	-10000	0	0
tube morphogenesis	-0.001	0.018	-10000	0	-10000	0	0
ruffle organization	0.024	0.019	-10000	0	-10000	0	0
regulation of epithelial cell migration	-0.001	0.006	-10000	0	-10000	0	0
PLD2	0.018	0.005	-10000	0	-10000	0	0
PIP5K1A	-0.001	0.016	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.023	0.028	-10000	0	-0.33	3	3
Rac1/GTP	-0.001	0.018	-10000	0	-10000	0	0

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.066	0.037	-10000	0	-10000	0	0
CRKL	0.039	0.038	-10000	0	-10000	0	0
mol:DAG	-0.004	0.033	-10000	0	-10000	0	0
HRAS	-0.003	0.025	-10000	0	-10000	0	0
MAPK8	0.028	0.045	-10000	0	-0.44	2	2
RAP1A	0.039	0.038	-10000	0	-10000	0	0
GAB1	0.039	0.038	-10000	0	-10000	0	0
MAPK14	0.028	0.045	-10000	0	-0.44	2	2
EPO	0.004	0.063	-10000	0	-0.57	6	6
PLCG1	-0.005	0.034	-10000	0	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0.012	0.004	-10000	0	-10000	0	0
RAPGEF1	0	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.006	0.047	-10000	0	-0.49	2	2
GAB1/SHC/GRB2/SOS1	-0.003	0.027	-10000	0	-10000	0	0
EPO/EPOR (dimer)	-0.003	0.045	-10000	0	-0.4	6	6
IRS2	0.037	0.049	-10000	0	-10000	0	0
STAT1	0.052	0.041	-10000	0	-10000	0	0
STAT5B	-0.005	0.034	-10000	0	-10000	0	0
cell proliferation	0.034	0.042	-10000	0	-0.4	2	2
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.004	0.029	-10000	0	-10000	0	0
TEC	0.038	0.046	-10000	0	-10000	0	0
SOCS3	-0.003	0.046	-10000	0	-0.74	2	2
STAT1 (dimer)	0.051	0.04	-10000	0	-10000	0	0
JAK2	0.011	0.004	-10000	0	-10000	0	0
PIK3R1	0	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.041	0.04	-10000	0	-0.37	2	2
EPO/EPOR	-0.003	0.045	-10000	0	-0.4	6	6
LYN	0.009	0.047	-10000	0	-0.74	2	2
TEC/VAV2	0.041	0.064	-10000	0	-0.72	2	2
elevation of cytosolic calcium ion concentration	0.012	0.004	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	0.024	0.05	-10000	0	-0.49	2	2
mol:IP3	-0.004	0.033	-10000	0	-10000	0	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.006	0.041	-10000	0	-10000	0	0
SH2B3	0.009	0.047	-10000	0	-0.73	2	2
NFKB1	0.028	0.045	-10000	0	-0.44	2	2
EPO/EPOR (dimer)/JAK2/SOCS3	-0.002	0.031	0.3	2	-10000	0	2
PTPN6	0.033	0.039	-10000	0	-0.36	2	2
TEC/VAV2/GRB2	-0.007	0.055	-10000	0	-0.7	2	2
EPOR	0.012	0.004	-10000	0	-10000	0	0
INPP5D	-0.001	0.033	-10000	0	-0.74	1	1
mol:GDP	-0.003	0.027	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
PLCG2	0	0	-10000	0	-10000	0	0
CRKL/CBL/C3G	-0.004	0.029	-10000	0	-10000	0	0
VAV2	0.037	0.055	-10000	0	-0.74	1	1
CBL	0.039	0.038	-10000	0	-10000	0	0
SHC/Grb2/SOS1	-0.004	0.029	-10000	0	-10000	0	0
STAT5A	-0.005	0.034	-10000	0	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
STAT5 (dimer)	0.063	0.042	-10000	0	-10000	0	0
LYN/PLCgamma2	-0.002	0.035	-10000	0	-0.55	2	2
PTPN11	0	0	-10000	0	-10000	0	0
BTK	-0.002	0.13	-10000	0	-0.74	2	2
BCL2	0.066	0.039	-10000	0	-10000	0	0

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0	0	-10000	0	-10000	0	0
mol:PIP3	0.001	0.02	0.31	2	-10000	0	2
FRAP1	0.014	0.007	-10000	0	-10000	0	0
AKT1	0.001	0.015	0.23	2	-10000	0	2
INSR	0	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0	0	-10000	0	-10000	0	0
TSC2	0	0	-10000	0	-10000	0	0
RHEB/GDP	0	0	-10000	0	-10000	0	0
TSC1	0	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0	0	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0	0	-10000	0	-10000	0	0
RPS6KB1	0.026	0.01	-10000	0	-10000	0	0
MAP3K5	0.009	0	-10000	0	-10000	0	0
PIK3R1	0	0	-10000	0	-10000	0	0
apoptosis	0.009	0	-10000	0	-10000	0	0
mol:LY294002	0	0	-10000	0	-10000	0	0
EIF4B	0.03	0.01	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0	0	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	0	0	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.029	0.009	0.17	2	-10000	0	2
FKBP1A	0	0.001	-10000	0	-10000	0	0
RHEB/GTP	0	0	-10000	0	-10000	0	0
mol:Amino Acids	0	0	-10000	0	-10000	0	0
FKBP12/Rapamycin	0	0.001	-10000	0	-10000	0	0
PDPK1	0.001	0.016	0.25	2	-10000	0	2
EIF4E	0	0	-10000	0	-10000	0	0
ASK1/PP5C	0	0.006	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.014	0.001	-10000	0	-10000	0	0
TSC1/TSC2	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RPS6	0	0	-10000	0	-10000	0	0
PPP5C	0	0	-10000	0	-10000	0	0
EIF4G1	0	0	-10000	0	-10000	0	0
IRS1	0.007	0.001	-10000	0	-10000	0	0
INS	0	0	-10000	0	-10000	0	0
PTEN	-0.003	0.046	-10000	0	-0.74	2	2
PDK2	0.001	0.016	0.25	2	-10000	0	2
EIF4EBP1	0.004	0.021	-10000	0	-10000	0	0
PIK3CA	0	0	-10000	0	-10000	0	0
PPP2R5D	0.02	0.006	-10000	0	-10000	0	0
peptide biosynthetic process	0.015	0	-10000	0	-10000	0	0
RHEB	0	0	-10000	0	-10000	0	0
EIF4A1	0	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	0.004	2	-10000	0	2
EEF2	0.015	0	-10000	0	-10000	0	0
eIF4E/4E-BP1	-0.004	0.015	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	0.02	0	-9999	-10000	0	0
BAD/BCL-XL/YWHAZ	0	0	-9999	-10000	0	0
CDKN1B	0.033	0	-9999	-10000	0	0
CDKN1A	0.033	0	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
PRKDC	0	0	-9999	-10000	0	0
FOXO3	0.033	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
BAD	0	0	-9999	-10000	0	0
AKT3	0.012	0.033	-9999	-0.42	3	3
mol:GTP	0	0	-9999	-10000	0	0
FOXO4	0.033	0	-9999	-10000	0	0
AKT1/ASK1	0	0	-9999	-10000	0	0
BAD/YWHAZ	0	0	-9999	-10000	0	0
RICTOR	0	0	-9999	-10000	0	0
RAF1	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
TSC1	0.033	0	-9999	-10000	0	0
YWHAZ	0	0	-9999	-10000	0	0
AKT1/RAF1	0	0	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
TSC2	0.033	0	-9999	-10000	0	0
YWHAQ	0	0	-9999	-10000	0	0
TBC1D4	0.022	0	-9999	-10000	0	0
MAP3K5	0	0	-9999	-10000	0	0
MAPKAP1	0	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.03	0.025	-9999	-10000	0	0
YWHAH	0	0	-9999	-10000	0	0
AKT1S1	0.033	0	-9999	-10000	0	0
CASP9	0.033	0	-9999	-10000	0	0
YWHAB	0	0	-9999	-10000	0	0
p27Kip1/KPNA1	0	0	-9999	-10000	0	0
GBL	0	0	-9999	-10000	0	0
PDK1/Src/Hsp90	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
AKT2/p21CIP1	0	0	-9999	-10000	0	0
KIAA1303	0	0	-9999	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.015	0	-9999	-10000	0	0
CHUK	0.033	0	-9999	-10000	0	0
BAD/BCL-XL	0	0	-9999	-10000	0	0
mTORC2	0	0	-9999	-10000	0	0
AKT2	0.015	0	-9999	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.043	0.027	-9999	-10000	0	0
PDPK1	0	0	-9999	-10000	0	0
MDM2	0.032	0.014	-9999	-10000	0	0
MAPKKK cascade	0	0	-9999	-10000	0	0
MDM2/Cbp/p300	0	0.011	-9999	-10000	0	0
TSC1/TSC2	0.039	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0.01	-9999	-10000	0	0
glucose import	0.024	0.04	-9999	-0.43	4	4
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.028	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	0.024	0.041	-9999	-0.43	4	4
GSK3A	0.033	0	-9999	-10000	0	0
FOXO1	0.033	0	-9999	-10000	0	0
GSK3B	0.033	0	-9999	-10000	0	0
SFN	-0.057	0.17	-9999	-0.58	49	49
G1/S transition of mitotic cell cycle	0.039	0	-9999	-10000	0	0
p27Kip1/14-3-3 family	0.029	0.039	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
KPNA1	0	0	-9999	-10000	0	0
HSP90AA1	0	0	-9999	-10000	0	0
YWHAG	0	0	-9999	-10000	0	0
RHEB	0	0	-9999	-10000	0	0
CREBBP	0	0	-9999	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.037	0.056	-9999	-0.53	1	1
BAG4	-0.001	0.026	-9999	-0.57	1	1
BAD	0.027	0.021	-9999	-10000	0	0
NFKBIA	0	0	-9999	-10000	0	0
BIRC3	-0.009	0.08	-9999	-0.74	6	6
BAX	0.027	0.021	-9999	-10000	0	0
EnzymeConsortium:3.1.4.12	0.012	0.015	-9999	-0.12	1	1
IKBKB	0.042	0.055	-9999	-0.49	1	1
MAP2K2	0.038	0.022	-9999	-10000	0	0
MAP2K1	0.038	0.022	-9999	-10000	0	0
SMPD1	0.017	0.015	-9999	-10000	0	0
GO:0005551	0	0	-9999	-10000	0	0
FADD/Caspase 8	0.043	0.055	-9999	-0.51	1	1
MAP2K4	0.033	0.021	-9999	-10000	0	0
protein ubiquitination	0.044	0.054	-9999	-0.5	1	1
EnzymeConsortium:2.7.1.37	0.043	0.025	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
RAF1	0.033	0.022	-9999	-10000	0	0
CRADD	0.01	0.001	-9999	-10000	0	0
mol:ceramide	0.021	0.021	-9999	-0.16	1	1
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-9999	-10000	0	0
MADD	0.01	0.001	-9999	-10000	0	0
MAP3K1	0.027	0.021	-9999	-10000	0	0
TRADD	0.01	0.001	-9999	-10000	0	0
RELA/p50	0	0	-9999	-10000	0	0
MAPK3	0.04	0.022	-9999	-10000	0	0
MAPK1	0.04	0.022	-9999	-10000	0	0
p50/RELA/I-kappa-B-alpha	0	0	-9999	-10000	0	0
FADD	0.037	0.056	-9999	-0.53	1	1
KSR1	0.028	0.022	-9999	-10000	0	0
MAPK8	0.038	0.02	-9999	-10000	0	0
TRAF2	0	0.001	-9999	-10000	0	0
response to radiation	0	0	-9999	-10000	0	0
CHUK	0.042	0.053	-9999	-0.49	1	1
TNF R/SODD	-0.001	0.019	-9999	-0.42	1	1
TNF	-0.009	0.12	-9999	-0.72	13	13
CYCS	0.028	0.02	-9999	-10000	0	0
IKBKG	0.042	0.053	-9999	-0.49	1	1
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.031	0.059	-9999	-0.56	1	1
RELA	0	0	-9999	-10000	0	0
RIPK1	0	0.001	-9999	-10000	0	0
AIFM1	0.028	0.02	-9999	-10000	0	0
TNF/TNF R/SODD	-0.013	0.076	-9999	-0.46	14	14
TNFRSF1A	0	0.001	-9999	-10000	0	0
response to heat	0	0	-9999	-10000	0	0
CASP8	0.023	0.015	-9999	-10000	0	0
NSMAF	0.037	0.055	-9999	-0.52	1	1
response to hydrogen peroxide	0	0	-9999	-10000	0	0
BCL2	-0.001	0.026	-9999	-0.57	1	1

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0	0	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	-0.001	0.015	-9999	-0.34	1	1
NF kappa B1 p50/RelA/I kappa B alpha	-0.001	0.017	-9999	-10000	0	0
NFKBIA	0.025	0.018	-9999	-0.26	2	2
MAPK14	0	0	-9999	-10000	0	0
NF kappa B1 p105/p50	-0.001	0.015	-9999	-0.34	1	1
ARRB2	0.015	0	-9999	-10000	0	0
REL	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	-0.001	0.015	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	-0.001	0.015	-9999	-0.34	1	1
PIK3CA	0	0	-9999	-10000	0	0
NF kappa B1 p50 dimer	-0.001	0.019	-9999	-0.42	1	1
PIK3R1	0	0	-9999	-10000	0	0
NFKB1	0.019	0.019	-9999	-0.42	1	1
RELA	0	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.03	0.019	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	-0.001	0.017	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.001	0.017	-9999	-10000	0	0
IKBKB	-0.001	0.026	-9999	-0.57	1	1
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
SYK	-0.001	0.033	-9999	-0.74	1	1
I kappa B alpha/PIK3R1	-0.001	0.015	-9999	-10000	0	0
cell death	-0.001	0.016	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	-0.001	0.015	-9999	-0.34	1	1
LCK	-0.001	0.033	-9999	-0.74	1	1
BCL3	0	0	-9999	-10000	0	0

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	0	0	-9999	-10000	0	0
KLHL20	-0.004	0.03	-9999	-0.38	1	1
CYFIP2	-0.026	0.14	-9999	-0.74	18	18
Rac1/GDP	0.053	0.011	-9999	-10000	0	0
ENAH	0	0	-9999	-10000	0	0
AP1M1	0	0	-9999	-10000	0	0
RAP1B	0	0	-9999	-10000	0	0
RAP1A	0	0	-9999	-10000	0	0
CTNNB1	0	0	-9999	-10000	0	0
CDC42/GTP	0	0	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.007	0.035	-9999	-0.25	5	5
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.001	0.019	-9999	-0.43	1	1
RAPGEF1	0.048	0.002	-9999	-10000	0	0
CTNND1	0	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0	0	-9999	-10000	0	0
CRK	0.043	0.005	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin	0	0	-9999	-10000	0	0
alphaE/beta7 Integrin	-0.001	0.025	-9999	-0.56	1	1
IQGAP1	0	0	-9999	-10000	0	0
NCKAP1	0	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0	0	-9999	-10000	0	0
DLG1	0	0	-9999	-10000	0	0
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
MLLT4	0	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.002	0.024	-9999	-0.38	2	2
PI3K	0	0	-9999	-10000	0	0
ARF6	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	0	0	-9999	-10000	0	0
TIAM1	-0.001	0.033	-9999	-0.74	1	1
E-cadherin(dimer)/Ca2+	0	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
CDH1	0	0	-9999	-10000	0	0
RhoA/GDP	0.053	0.01	-9999	-10000	0	0
actin cytoskeleton organization	-0.003	0.022	-9999	-0.26	1	1
CDC42/GDP	0.053	0.01	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0	0	-9999	-10000	0	0
ITGB7	-0.001	0.033	-9999	-0.74	1	1
RAC1	0	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin	0	0	-9999	-10000	0	0
mol:GDP	0.052	0.012	-9999	-10000	0	0
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	0	0	-9999	-10000	0	0
p120 catenin/RhoA/GDP	0	0.006	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0
CTNNA1	0	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	-0.004	0.03	-9999	-0.25	7	7
NME1	-0.001	0.026	-9999	-0.57	1	1
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0	0	-9999	-10000	0	0
regulation of cell-cell adhesion	0	0	-9999	-10000	0	0
WASF2	-0.004	0.018	-9999	-0.14	1	1
Rap1/GTP	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.001	0.018	-9999	-0.4	1	1
CCND1	-0.005	0.038	-9999	-0.32	7	7
VAV2	0.041	0.061	-9999	-0.74	3	3
RAP1/GDP	0	0.001	-9999	-10000	0	0
adherens junction assembly	0	0	-9999	-10000	0	0
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0	0	-9999	-10000	0	0
PIP5K1C	0	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.001	0.017	-9999	-10000	0	0
E-cadherin/beta catenin	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
Rac1/GTP	-0.007	0.052	-9999	-0.49	3	3
E-cadherin/beta catenin/alpha catenin	0	0	-9999	-10000	0	0
ITGAE	0	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0	0	-9999	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
MDM2/SUMO1	-0.001	0.013	-9999	-10000	0	0
HDAC4	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
SUMO1	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.025	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0	0	-9999	-10000	0	0
SUMO1/HDAC4	0	0	-9999	-10000	0	0
SUMO1/HDAC1	0	0	-9999	-10000	0	0
RANGAP1	0	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	-0.001	0.014	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0	0	-9999	-10000	0	0
Ran/GTP	0	0	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	-0.001	0.026	-9999	-0.57	1	1
UBE2I	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
PIAS2	0	0	-9999	-10000	0	0
PIAS1	0	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

E-cadherin signaling events

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

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

Entity	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
E-cadherin/beta catenin-gamma catenin	-9999	-9999
E-cadherin/beta catenin	-9999	-9999
CTNNB1	-9999	-9999
JUP	-9999	-9999
CDH1	-9999	-9999

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0	0	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.018	0	-9999	-10000	0	0
AP2	-0.001	0.019	-9999	-0.42	1	1
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0	-9999	-10000	0	0
CLTB	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0	0	-9999	-10000	0	0
CD4	-0.022	0.13	-9999	-0.74	15	15
CLTA	0	0	-9999	-10000	0	0
mol:GTP	0.001	0	-9999	-10000	0	0
ARFGAP1	0.01	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
ARF1/GTP	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0	0	-9999	-10000	0	0
mol:Choline	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0	0	-9999	-10000	0	0
DDEF1	0	0	-9999	-10000	0	0
ARF1/GDP	0	0	-9999	-10000	0	0
AP2M1	-0.001	0.026	-9999	-0.57	1	1
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0	0	-9999	-10000	0	0
Rac/GTP	0	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0	0	-9999	-10000	0	0
ARFIP2	0	0	-9999	-10000	0	0
COPA	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.022	0	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0	-9999	-10000	0	0
GGA3	0	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0	0	-9999	-10000	0	0
AP2A1	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0	0	-9999	-10000	0	0
CYTH2	0	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0	0	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0	0	-9999	-10000	0	0
mol:Brefeldin A	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	-0.008	0.044	-9999	-10000	0	0
PLD2	0	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.01	0	-9999	-10000	0	0
PIP5K1A	0	0	-9999	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0	0	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	0.01	0	-9999	-10000	0	0
GOSR2	0	0	-9999	-10000	0	0
USO1	0	0	-9999	-10000	0	0
GBF1	0	0	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	-0.015	0.082	-9999	-0.48	15	15

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0	0	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
CHUK	0	0	-9999	-10000	0	0
NF kappa B2 p100/RelB	-0.001	0.013	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
MAP3K14	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelB	-0.001	0.019	-9999	-0.42	1	1
RELB	-0.001	0.026	-9999	-0.57	1	1
NFKB2	0	0	-9999	-10000	0	0
NF kappa B2 p52/RelB	-0.001	0.016	-9999	-0.35	1	1
regulation of B cell activation	-0.001	0.016	-9999	-0.35	1	1

pid_entity	TCGA.XC.AA0X	TCGA.O2.A5IB	TCGA.O2.A52W	TCGA.O2.A52V
109_MAP3K5	0.048	0.048	0.048	0.048
47_PPARGC1A	0	0	0	0
105_BMP4	0	0	0	0
105_BMP6	0	0	0	0
105_BMP7	-0.58	0	-0.58	-0.58
105_BMP2	0	-0.74	0	0
131_RELN/VLDLR	0	0	0	0
30_TGFB1/TGF beta receptor Type II	0.014	0.016	0.014	0.014
84_STAT5B	0.023	-0.0056	0.038	0.038
84_STAT5A	0.023	-0.0056	0.038	0.038