PARADIGM pathway analysis of mRNASeq expression data - Skin Cutaneous Melanoma (Metastatic)

Pathway.Name	Avg.Num.Perturbations
IL4-mediated signaling events	139
BCR signaling pathway	136
TCR signaling in naïve CD8+ T cells	103
IL23-mediated signaling events	102
Nephrin/Neph1 signaling in the kidney podocyte	91
IL12-mediated signaling events	80
Caspase cascade in apoptosis	65
FAS signaling pathway (CD95)	65
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	63
E-cadherin signaling events	62

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
IL4-mediated signaling events	0.3798	139	12732	91	-1.3	1	1000	-1000	-0.1	-1000
BCR signaling pathway	0.3716	136	13536	99	-0.76	0.026	1000	-1000	-0.057	-1000
TCR signaling in naïve CD8+ T cells	0.2814	103	9621	93	-0.59	0.028	1000	-1000	-0.047	-1000
IL23-mediated signaling events	0.2787	102	6177	60	-0.74	0.019	1000	-1000	-0.051	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.2486	91	3110	34	-0.21	0.019	1000	-1000	-0.013	-1000
IL12-mediated signaling events	0.2186	80	7003	87	-0.68	0.11	1000	-1000	-0.091	-1000
Caspase cascade in apoptosis	0.1776	65	4881	74	-0.21	0.14	1000	-1000	-0.026	-1000
FAS signaling pathway (CD95)	0.1776	65	3095	47	-0.16	0.12	1000	-1000	-0.012	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.1721	63	4308	68	-0.62	0.12	1000	-1000	-0.044	-1000
E-cadherin signaling events	0.1694	62	314	5	-0.13	0.019	1000	-1000	-0.005	-1000
Calcium signaling in the CD4+ TCR pathway	0.1585	58	1807	31	-0.43	0.019	1000	-1000	-0.038	-1000
JNK signaling in the CD4+ TCR pathway	0.1530	56	959	17	-0.2	0.019	1000	-1000	-0.015	-1000
Ras signaling in the CD4+ TCR pathway	0.1530	56	952	17	-0.17	0.037	1000	-1000	-0.011	-1000
IL27-mediated signaling events	0.1448	53	2704	51	-0.27	0.16	1000	-1000	-0.037	-1000
S1P4 pathway	0.1448	53	1330	25	-0.16	0.028	1000	-1000	-0.008	-1000
Glypican 1 network	0.1366	50	2429	48	-0.3	0.068	1000	-1000	-0.017	-1000
Signaling events regulated by Ret tyrosine kinase	0.1339	49	4078	82	-0.13	0.019	1000	-1000	-0.053	-1000
Wnt signaling	0.1311	48	341	7	-0.082	0.008	1000	-1000	-0.011	-1000
amb2 Integrin signaling	0.1257	46	3806	82	-0.27	0.026	1000	-1000	-0.025	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.1257	46	3466	74	-0.13	0.05	1000	-1000	-0.05	-1000
a4b1 and a4b7 Integrin signaling	0.1202	44	222	5	-0.076	-0.019	1000	-1000	-0.002	-1000
Glucocorticoid receptor regulatory network	0.1148	42	4892	114	-0.52	0.31	1000	-1000	-0.041	-1000
Thromboxane A2 receptor signaling	0.1120	41	4340	105	-0.12	0.041	1000	-1000	-0.039	-1000
Endothelins	0.1120	41	3951	96	-0.18	0.02	1000	-1000	-0.04	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.1120	41	1855	45	-0.28	0.046	1000	-1000	-0.051	-1000
TCGA08_retinoblastoma	0.1120	41	331	8	-0.11	0.03	1000	-1000	-0.005	-1000
E-cadherin signaling in the nascent adherens junction	0.1093	40	3043	76	-0.13	0.028	1000	-1000	-0.055	-1000
Syndecan-4-mediated signaling events	0.1093	40	2681	67	-0.26	0.025	1000	-1000	-0.021	-1000
Angiopoietin receptor Tie2-mediated signaling	0.1066	39	3471	88	-0.23	0.03	1000	-1000	-0.056	-1000
IL2 signaling events mediated by PI3K	0.1038	38	2241	58	-0.19	0.046	1000	-1000	-0.021	-1000
IL2 signaling events mediated by STAT5	0.1038	38	839	22	-0.19	0.02	1000	-1000	-0.022	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.1011	37	1387	37	-0.29	0.041	1000	-1000	-0.015	-1000
Regulation of p38-alpha and p38-beta	0.1011	37	2012	54	-0.34	0.049	1000	-1000	-0.034	-1000
LPA receptor mediated events	0.0956	35	3659	102	-0.13	0.025	1000	-1000	-0.051	-1000
Class I PI3K signaling events	0.0929	34	2506	73	-0.45	0.048	1000	-1000	-0.023	-1000
Fc-epsilon receptor I signaling in mast cells	0.0874	32	3137	97	-0.13	0.033	1000	-1000	-0.05	-1000
HIF-1-alpha transcription factor network	0.0847	31	2401	76	-0.12	0.084	1000	-1000	-0.045	-1000
Ephrin A reverse signaling	0.0820	30	213	7	-0.071	0.008	1000	-1000	-0.004	-1000
Atypical NF-kappaB pathway	0.0792	29	900	31	-0.2	0.033	1000	-1000	-0.007	-1000
Syndecan-1-mediated signaling events	0.0765	28	961	34	-0.15	0.019	1000	-1000	-0.018	-1000
Visual signal transduction: Cones	0.0765	28	1087	38	-0.21	0.017	1000	-1000	-0.007	-1000
ceramide signaling pathway	0.0765	28	1394	49	-0.18	0.028	1000	-1000	-0.013	-1000
Visual signal transduction: Rods	0.0765	28	1463	52	-0.21	0.019	1000	-1000	-0.039	-1000
TRAIL signaling pathway	0.0738	27	1303	48	-0.057	0.021	1000	-1000	-0.022	-1000
FOXA2 and FOXA3 transcription factor networks	0.0683	25	1176	46	-0.5	0.027	1000	-1000	-0.029	-1000
TCGA08_p53	0.0683	25	177	7	-0.071	0.051	1000	-1000	-0.005	-1000
Noncanonical Wnt signaling pathway	0.0656	24	645	26	-0.082	0.019	1000	-1000	-0.019	-1000
BMP receptor signaling	0.0656	24	1969	81	-0.23	0.059	1000	-1000	-0.059	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0628	23	660	28	-0.16	0.049	1000	-1000	-0.01	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0628	23	1226	52	-0.19	0.031	1000	-1000	-0.02	-1000
Aurora C signaling	0.0601	22	156	7	-0.098	0.017	1000	-1000	-0.01	-1000
IL6-mediated signaling events	0.0601	22	1701	75	-0.19	0.068	1000	-1000	-0.02	-1000
Arf6 signaling events	0.0546	20	1259	62	-0.18	0.045	1000	-1000	-0.016	-1000
Signaling events mediated by PTP1B	0.0546	20	1554	76	-0.34	0.032	1000	-1000	-0.032	-1000
IFN-gamma pathway	0.0546	20	1411	68	-0.18	0.028	1000	-1000	-0.056	-1000
Paxillin-dependent events mediated by a4b1	0.0546	20	734	36	-0.077	0.059	1000	-1000	-0.026	-1000
Osteopontin-mediated events	0.0519	19	756	38	-0.049	0.035	1000	-1000	-0.026	-1000
Syndecan-2-mediated signaling events	0.0519	19	1333	69	-0.26	0.046	1000	-1000	-0.019	-1000
p75(NTR)-mediated signaling	0.0519	19	2417	125	-0.18	0.054	1000	-1000	-0.051	-1000
Integrins in angiogenesis	0.0519	19	1656	84	-0.2	0.043	1000	-1000	-0.053	-1000
Effects of Botulinum toxin	0.0464	17	445	26	-0.066	0.026	1000	-1000	-0.015	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0464	17	1361	78	-0.15	0.056	1000	-1000	-0.023	-1000
EPO signaling pathway	0.0437	16	898	55	-0.079	0.029	1000	-1000	-0.047	-1000
EPHB forward signaling	0.0437	16	1440	85	-0.059	0.041	1000	-1000	-0.048	-1000
EGFR-dependent Endothelin signaling events	0.0437	16	348	21	-0.031	0.028	1000	-1000	-0.039	-1000
Signaling events mediated by the Hedgehog family	0.0410	15	805	52	-0.28	0.044	1000	-1000	-0.015	-1000
Cellular roles of Anthrax toxin	0.0410	15	611	39	-0.15	0.019	1000	-1000	-0.008	-1000
Nectin adhesion pathway	0.0410	15	951	63	-0.24	0.045	1000	-1000	-0.043	-1000
Ceramide signaling pathway	0.0410	15	1169	76	-0.18	0.042	1000	-1000	-0.012	-1000
E-cadherin signaling in keratinocytes	0.0410	15	665	43	-0.13	0.022	1000	-1000	-0.02	-1000
S1P5 pathway	0.0383	14	254	17	-0.094	0.019	1000	-1000	-0.005	-1000
Plasma membrane estrogen receptor signaling	0.0383	14	1273	86	-0.094	0.048	1000	-1000	-0.048	-1000
Coregulation of Androgen receptor activity	0.0355	13	1048	76	-0.11	0.038	1000	-1000	-0.021	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0355	13	1111	85	-0.075	0.041	1000	-1000	-0.05	-1000
Ephrin B reverse signaling	0.0355	13	658	48	-0.12	0.021	1000	-1000	-0.029	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0355	13	1111	83	-0.16	0.085	1000	-1000	-0.02	-1000
Nongenotropic Androgen signaling	0.0355	13	694	52	-0.094	0.037	1000	-1000	-0.025	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0355	13	1643	120	-0.12	0.078	1000	-1000	-0.043	-1000
LPA4-mediated signaling events	0.0328	12	155	12	-0.056	0.02	1000	-1000	-0.007	-1000
Reelin signaling pathway	0.0328	12	704	56	-0.1	0.052	1000	-1000	-0.048	-1000
IL1-mediated signaling events	0.0328	12	744	62	-0.069	0.07	1000	-1000	-0.049	-1000
Syndecan-3-mediated signaling events	0.0301	11	410	35	-0.054	0.054	1000	-1000	-0.02	-1000
Glypican 2 network	0.0301	11	47	4	0.004	0.01	1000	-1000	-0.006	-1000
S1P3 pathway	0.0301	11	488	42	-0.092	0.037	1000	-1000	-0.017	-1000
ErbB2/ErbB3 signaling events	0.0273	10	713	65	-0.023	0.042	1000	-1000	-0.041	-1000
Presenilin action in Notch and Wnt signaling	0.0273	10	617	61	-0.11	0.055	1000	-1000	-0.029	-1000
S1P1 pathway	0.0273	10	364	36	-0.094	0.021	1000	-1000	-0.038	-1000
Canonical Wnt signaling pathway	0.0273	10	519	51	-0.078	0.071	1000	-1000	-0.026	-1000
ErbB4 signaling events	0.0246	9	683	69	-0.12	0.052	1000	-1000	-0.049	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0246	9	496	54	-0.13	0.033	1000	-1000	-0.056	-1000
Regulation of Androgen receptor activity	0.0246	9	681	70	-0.14	0.056	1000	-1000	-0.026	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0219	8	266	33	-0.11	0.055	1000	-1000	-0.017	-1000
Rapid glucocorticoid signaling	0.0219	8	170	20	-0.02	0.02	1000	-1000	-0.004	-1000
PDGFR-beta signaling pathway	0.0219	8	861	97	-0.34	0.061	1000	-1000	-0.05	-1000
Regulation of nuclear SMAD2/3 signaling	0.0191	7	1021	136	-0.11	0.082	1000	-1000	-0.026	-1000
Signaling events mediated by HDAC Class I	0.0164	6	669	104	-0.095	0.063	1000	-1000	-0.026	-1000
Signaling mediated by p38-gamma and p38-delta	0.0164	6	104	15	-0.03	0.027	1000	-1000	-0.012	-1000
Signaling mediated by p38-alpha and p38-beta	0.0164	6	301	44	-0.038	0.028	1000	-1000	-0.007	-1000
Regulation of Telomerase	0.0164	6	706	102	-0.17	0.069	1000	-1000	-0.053	-1000
Insulin Pathway	0.0164	6	459	74	-0.061	0.048	1000	-1000	-0.051	-1000
Signaling events mediated by PRL	0.0164	6	206	34	-0.089	0.049	1000	-1000	-0.016	-1000
Class IB PI3K non-lipid kinase events	0.0164	6	18	3	-0.01	0.01	1000	-1000	-0.003	-1000
Aurora B signaling	0.0164	6	445	67	-0.15	0.057	1000	-1000	-0.029	-1000
Canonical NF-kappaB pathway	0.0137	5	232	39	-0.095	0.085	1000	-1000	-0.049	-1000
Hedgehog signaling events mediated by Gli proteins	0.0137	5	388	65	-0.093	0.085	1000	-1000	-0.044	-1000
TCGA08_rtk_signaling	0.0137	5	145	26	-0.056	0.05	1000	-1000	-0.007	-1000
FOXM1 transcription factor network	0.0137	5	270	51	-0.11	0.29	1000	-1000	-0.11	-1000
PDGFR-alpha signaling pathway	0.0109	4	202	44	-0.013	0.041	1000	-1000	-0.012	-1000
Signaling events mediated by HDAC Class III	0.0109	4	199	40	-0.094	0.035	1000	-1000	-0.012	-1000
Insulin-mediated glucose transport	0.0082	3	117	32	-0.034	0.049	1000	-1000	-0.019	-1000
FoxO family signaling	0.0082	3	201	64	-0.43	0.18	1000	-1000	-0.032	-1000
Retinoic acid receptors-mediated signaling	0.0082	3	225	58	-0.05	0.057	1000	-1000	-0.039	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0082	3	415	125	-0.12	0.082	1000	-1000	-0.059	-1000
p38 MAPK signaling pathway	0.0082	3	152	44	-0.046	0.042	1000	-1000	-0.043	-1000
Signaling events mediated by HDAC Class II	0.0055	2	182	75	-0.063	0.054	1000	-1000	-0.024	-1000
Arf6 downstream pathway	0.0055	2	91	43	-0.031	0.036	1000	-1000	-0.021	-1000
IGF1 pathway	0.0055	2	114	57	-0.046	0.054	1000	-1000	-0.052	-1000
Aurora A signaling	0.0027	1	102	60	-0.023	0.052	1000	-1000	-0.009	-1000
Class I PI3K signaling events mediated by Akt	0.0027	1	86	68	-0.044	0.059	1000	-1000	-0.022	-1000
HIF-2-alpha transcription factor network	0.0027	1	75	43	-0.16	0.16	1000	-1000	-0.047	-1000
Arf6 trafficking events	0.0027	1	119	71	-0.028	0.049	1000	-1000	-0.036	-1000
VEGFR1 specific signals	0.0027	1	111	56	-0.052	0.064	1000	-1000	-0.022	-1000
Arf1 pathway	0.0027	1	105	54	-0.034	0.034	1000	-1000	-0.01	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	0	23	0.015	0.056	1000	-1000	-0.015	-1000
BARD1 signaling events	0.0000	0	4	57	-0.047	0.08	1000	-1000	-0.015	-1000
PLK2 and PLK4 events	0.0000	0	2	3	0.017	0.025	1000	-1000	0	-1000
Circadian rhythm pathway	0.0000	0	12	22	-0.016	0.06	1000	-1000	-0.024	-1000
PLK1 signaling events	0.0000	0	45	85	-0.013	0.05	1000	-1000	-0.024	-1000
mTOR signaling pathway	0.0000	0	18	53	-0.005	0.041	1000	-1000	-0.039	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	9	27	-0.001	0.046	1000	-1000	-0.031	-1000
Alternative NF-kappaB pathway	0.0000	0	0	13	0	0.056	1000	-1000	-0.005	-1000
Total	NA	3147	187721	7203	-22	7.6	131000	-131000	-3.9	-131000

IL4-mediated signaling events

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
BCL2L1	-0.89	0.59	-10000	0	-1.3	230	230
STAT6 (cleaved dimer)	-0.98	0.6	-10000	0	-1.3	265	265
IGHG1	-0.25	0.16	-10000	0	-0.35	194	194
IGHG3	-0.87	0.56	-10000	0	-1.2	254	254
AKT1	-0.54	0.45	-10000	0	-0.94	166	166
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.58	0.61	-10000	0	-1.3	129	129
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.61	0.54	-10000	0	-0.99	192	192
THY1	-0.89	0.59	-10000	0	-1.3	224	224
MYB	-0.01	0.12	-10000	0	-0.54	19	19
HMGA1	0.017	0.029	-10000	0	-0.54	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.66	0.54	-10000	0	-0.94	238	238
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.64	0.59	-10000	0	-1.1	188	188
SP1	0.022	0.013	-10000	0	-10000	0	0
INPP5D	-0.075	0.21	-10000	0	-0.54	62	62
SOCS5	0.034	0.015	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.95	0.64	-10000	0	-1.3	250	250
SOCS1	-0.55	0.35	-10000	0	-0.78	234	234
SOCS3	-0.51	0.4	-10000	0	-0.95	131	131
FCER2	-1.3	0.69	-10000	0	-1.6	295	295
PARP14	0.007	0.051	-10000	0	-0.54	3	3
CCL17	-0.92	0.62	-10000	0	-1.3	233	233
GRB2	0.019	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.48	0.44	-10000	0	-0.96	132	132
T cell proliferation	-0.94	0.63	-10000	0	-1.3	241	241
IL4R/JAK1	-0.9	0.59	-10000	0	-1.3	236	236
EGR2	-1	0.61	-10000	0	-1.3	257	257
JAK2	-0.037	0.076	-10000	0	-0.53	7	7
JAK3	-0.013	0.14	-10000	0	-0.51	25	25
PIK3R1	0.019	0	-10000	0	-10000	0	0
JAK1	0.005	0.013	-10000	0	-10000	0	0
COL1A2	-0.26	0.19	-10000	0	-0.57	47	47
CCL26	-0.9	0.58	-10000	0	-1.3	228	228
IL4R	-0.96	0.64	-10000	0	-1.4	235	235
PTPN6	-0.1	0.24	-10000	0	-0.52	92	92
IL13RA2	-0.95	0.6	-10000	0	-1.3	250	250
IL13RA1	-0.026	0.03	-10000	0	-10000	0	0
IRF4	-0.7	0.61	-10000	0	-1.2	202	202
ARG1	-0.22	0.21	-10000	0	-0.73	34	34
CBL	-0.61	0.49	-10000	0	-0.88	230	230
GTF3A	0.02	0.015	-10000	0	-10000	0	0
PIK3CA	0.018	0.014	-10000	0	-0.24	1	1
IL13RA1/JAK2	-0.041	0.065	-10000	0	-0.39	7	7
IRF4/BCL6	-0.6	0.56	-10000	0	-1.1	202	202
CD40LG	-0.28	0.28	-10000	0	-0.54	195	195
MAPK14	-0.6	0.49	-10000	0	-0.89	226	226
mitosis	-0.49	0.41	-10000	0	-0.86	166	166
STAT6	-1.1	0.8	-10000	0	-1.5	244	244
SPI1	-0.023	0.15	-10000	0	-0.54	28	28
RPS6KB1	-0.47	0.39	-10000	0	-0.85	151	151
STAT6 (dimer)	-1.1	0.81	-10000	0	-1.5	244	244
STAT6 (dimer)/PARP14	-1.1	0.7	-10000	0	-1.4	262	262
mast cell activation	0.018	0.012	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.62	0.59	-10000	0	-1.1	178	178
FRAP1	-0.54	0.46	-10000	0	-0.94	166	166
LTA	-1.1	0.73	-10000	0	-1.6	243	243
FES	0.007	0.081	-10000	0	-0.54	8	8
T-helper 1 cell differentiation	1	0.72	1.4	245	-10000	0	245
CCL11	-0.9	0.56	-10000	0	-1.2	241	241
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.61	0.57	-10000	0	-1.1	181	181
IL2RG	-0.14	0.25	-10000	0	-0.52	112	112
IL10	-0.92	0.61	-10000	0	-1.3	226	226
IRS1	-0.003	0.072	-10000	0	-0.24	30	30
IRS2	0.019	0	-10000	0	-10000	0	0
IL4	-0.17	0.11	-10000	0	-10000	0	0
IL5	-0.9	0.58	-10000	0	-1.3	234	234
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.66	0.41	-10000	0	-0.91	236	236
COL1A1	-0.29	0.21	-10000	0	-0.59	67	67
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.93	0.63	-10000	0	-1.3	225	225
IL2R gamma/JAK3	-0.12	0.23	-10000	0	-0.44	112	112
TFF3	-0.97	0.65	-10000	0	-1.4	241	241
ALOX15	-0.9	0.6	-10000	0	-1.3	233	233
MYBL1	0.016	0.041	-10000	0	-0.54	2	2
T-helper 2 cell differentiation	-0.83	0.58	-10000	0	-1.2	246	246
SHC1	0.019	0	-10000	0	-10000	0	0
CEBPB	0.02	0.011	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.59	0.54	-10000	0	-0.98	187	187
mol:PI-3-4-5-P3	-0.54	0.46	-10000	0	-0.94	166	166
PI3K	-0.59	0.53	-10000	0	-1.1	164	164
DOK2	-0.037	0.17	-10000	0	-0.54	37	37
ETS1	0.037	0.013	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.44	0.4	-10000	0	-0.91	128	128
ITGB3	-0.92	0.6	-10000	0	-1.3	235	235
PIGR	-0.98	0.66	-10000	0	-1.4	241	241
IGHE	0.057	0.039	0.28	2	-10000	0	2
MAPKKK cascade	-0.43	0.39	-10000	0	-0.88	128	128
BCL6	0.024	0.008	-10000	0	-10000	0	0
OPRM1	-0.9	0.58	-10000	0	-1.3	234	234
RETNLB	-0.9	0.58	-10000	0	-1.3	225	225
SELP	-1	0.7	-10000	0	-1.5	242	242
AICDA	-1.1	0.67	-10000	0	-1.5	267	267

×

BCR signaling pathway

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
JUN	-0.32	0.28	-10000	0	-0.52	227	227
IKBKB	-0.14	0.14	-10000	0	-0.27	137	137
AKT1	-0.18	0.15	-10000	0	-0.29	236	236
IKBKG	-0.14	0.15	-10000	0	-0.26	203	203
CALM1	-0.37	0.37	-10000	0	-0.62	218	218
PIK3CA	0.018	0.014	-10000	0	-0.24	1	1
MAP3K1	-0.49	0.4	-10000	0	-0.76	240	240
MAP3K7	0.019	0	-10000	0	-10000	0	0
mol:Ca2+	-0.41	0.4	-10000	0	-0.68	218	218
DOK1	0.019	0	-10000	0	-10000	0	0
AP-1	-0.16	0.15	-10000	0	-0.27	224	224
LYN	-0.004	0.11	-10000	0	-0.54	15	15
BLNK	-0.19	0.27	-10000	0	-0.54	140	140
SHC1	0.019	0	-10000	0	-10000	0	0
BCR complex	-0.39	0.33	-10000	0	-0.62	235	235
CD22	-0.62	0.51	-10000	0	-0.98	229	229
CAMK2G	-0.33	0.33	-10000	0	-0.56	218	218
CSNK2A1	0.019	0	-10000	0	-10000	0	0
INPP5D	-0.075	0.21	-10000	0	-0.54	62	62
SHC/GRB2/SOS1	-0.38	0.34	-10000	0	-0.65	202	202
GO:0007205	-0.42	0.42	-10000	0	-0.7	218	218
SYK	-0.052	0.19	-10000	0	-0.54	47	47
ELK1	-0.38	0.38	-10000	0	-0.64	218	218
NFATC1	-0.43	0.36	-10000	0	-0.68	236	236
B-cell antigen/BCR complex	-0.39	0.33	-10000	0	-0.62	235	235
PAG1/CSK	0.026	0.03	-10000	0	-0.38	2	2
NFKBIB	-0.031	0.046	-10000	0	-0.083	19	19
HRAS	-0.37	0.36	-10000	0	-0.62	218	218
NFKBIA	-0.031	0.046	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	-0.017	0.037	-10000	0	-10000	0	0
RasGAP/Csk	-0.28	0.27	-10000	0	-0.47	236	236
mol:GDP	-0.39	0.38	-10000	0	-0.65	218	218
PTEN	0.017	0.029	-10000	0	-0.54	1	1
CD79B	-0.27	0.28	-10000	0	-0.54	191	191
NF-kappa-B/RelA/I kappa B alpha	-0.016	0.037	-10000	0	-10000	0	0
GRB2	0.019	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.45	0.36	-10000	0	-0.7	236	236
PIK3R1	0.019	0	-10000	0	-10000	0	0
mol:IP3	-0.43	0.43	-10000	0	-0.72	218	218
CSK	0.019	0	-10000	0	-10000	0	0
FOS	-0.34	0.34	-10000	0	-0.57	221	221
CHUK	-0.14	0.15	-10000	0	-0.29	137	137
IBTK	0.019	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.34	0.34	-10000	0	-0.6	204	204
PTPN6	-0.62	0.52	-10000	0	-0.98	229	229
RELA	0.019	0	-10000	0	-10000	0	0
BCL2A1	-0.012	0.036	-10000	0	-0.1	22	22
VAV2	-0.66	0.52	-10000	0	-1	236	236
ubiquitin-dependent protein catabolic process	-0.025	0.045	-10000	0	-10000	0	0
BTK	-0.17	0.41	0.34	19	-1	65	84
CD19	-0.66	0.52	-10000	0	-1	237	237
MAP4K1	-0.081	0.21	-10000	0	-0.54	66	66
CD72	-0.14	0.25	-10000	0	-0.54	104	104
PAG1	0.016	0.041	-10000	0	-0.54	2	2
MAPK14	-0.38	0.32	-10000	0	-0.6	240	240
SH3BP5	0.019	0	-10000	0	-10000	0	0
PIK3AP1	-0.46	0.47	-10000	0	-0.76	224	224
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.59	0.64	-10000	0	-1	218	218
RAF1	-0.33	0.33	-10000	0	-0.58	209	209
RasGAP/p62DOK/SHIP	-0.31	0.31	-10000	0	-0.52	236	236
CD79A	-0.31	0.27	-10000	0	-0.54	214	214
re-entry into mitotic cell cycle	-0.16	0.15	-10000	0	-0.27	224	224
RASA1	0.017	0.029	-10000	0	-0.54	1	1
MAPK3	-0.26	0.26	-10000	0	-0.47	200	200
MAPK1	-0.26	0.26	-10000	0	-0.47	200	200
CD72/SHP1	-0.6	0.52	-10000	0	-0.96	230	230
NFKB1	0.019	0	-10000	0	-10000	0	0
MAPK8	-0.38	0.32	-10000	0	-0.6	240	240
actin cytoskeleton organization	-0.5	0.4	-10000	0	-0.78	236	236
NF-kappa-B/RelA	-0.026	0.072	-10000	0	-10000	0	0
Calcineurin	-0.29	0.3	-10000	0	-0.52	200	200
PI3K	-0.46	0.32	-10000	0	-0.67	245	245
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.49	0.5	-10000	0	-0.81	222	222
SOS1	0.019	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.62	0.53	-10000	0	-1	226	226
DAPP1	-0.76	0.65	-10000	0	-1.2	226	226
cytokine secretion	-0.39	0.32	-10000	0	-0.61	236	236
mol:DAG	-0.43	0.43	-10000	0	-0.72	218	218
PLCG2	-0.03	0.16	-10000	0	-0.54	32	32
MAP2K1	-0.3	0.3	-10000	0	-0.53	200	200
B-cell antigen/BCR complex/FcgammaRIIB	-0.34	0.3	-10000	0	-0.55	236	236
mol:PI-3-4-5-P3	-0.3	0.2	-10000	0	-0.43	245	245
ETS1	-0.29	0.29	-10000	0	-0.52	200	200
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.42	0.41	-10000	0	-0.68	237	237
B-cell antigen/BCR complex/LYN	-0.57	0.48	-10000	0	-0.88	236	236
MALT1	0.017	0.029	-10000	0	-0.54	1	1
TRAF6	0.019	0	-10000	0	-10000	0	0
RAC1	-0.56	0.45	-10000	0	-0.87	236	236
B-cell antigen/BCR complex/LYN/SYK	-0.59	0.51	-10000	0	-0.95	228	228
CARD11	-0.44	0.44	-10000	0	-0.73	223	223
FCGR2B	-0.005	0.11	-10000	0	-0.52	16	16
PPP3CA	0.019	0	-10000	0	-10000	0	0
BCL10	0.018	0.014	-10000	0	-0.24	1	1
IKK complex	-0.044	0.056	-10000	0	-0.097	122	122
PTPRC	-0.18	0.27	-10000	0	-0.54	131	131
PDPK1	-0.18	0.15	-10000	0	-0.28	245	245
PPP3CB	0.019	0	-10000	0	-10000	0	0
PPP3CC	0.019	0	-10000	0	-10000	0	0
POU2F2	-0.02	0.048	-10000	0	-0.11	62	62

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.27	0.4	-10000	0	-0.71	159	159
FYN	-0.44	0.59	-10000	0	-1.1	162	162
LAT/GRAP2/SLP76	-0.33	0.38	-10000	0	-0.74	163	163
IKBKB	0.019	0	-10000	0	-10000	0	0
AKT1	-0.2	0.31	-10000	0	-0.54	162	162
B2M	0.004	0.082	-10000	0	-0.55	8	8
IKBKG	-0.043	0.1	-10000	0	-0.16	153	153
MAP3K8	-0.003	0.11	-10000	0	-0.52	15	15
mol:Ca2+	-0.019	0.022	-10000	0	-0.077	10	10
integrin-mediated signaling pathway	-0.02	0.12	-10000	0	-0.32	48	48
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.35	0.5	-10000	0	-0.89	162	162
TRPV6	-0.01	0.053	-10000	0	-0.25	16	16
CD28	-0.071	0.2	-10000	0	-0.54	58	58
SHC1	-0.4	0.55	-10000	0	-1	160	160
receptor internalization	-0.48	0.64	-10000	0	-1.2	162	162
PRF1	-0.51	0.69	-10000	0	-1.3	146	146
KRAS	0.018	0.014	-10000	0	-0.24	1	1
GRB2	0.019	0	-10000	0	-10000	0	0
COT/AKT1	-0.15	0.25	-10000	0	-0.42	159	159
LAT	-0.41	0.56	-10000	0	-1	161	161
EntrezGene:6955	-0.002	0.005	-10000	0	-10000	0	0
CD3D	-0.22	0.28	-10000	0	-0.55	154	154
CD3E	-0.19	0.28	-10000	0	-0.55	136	136
CD3G	-0.18	0.27	-10000	0	-0.54	126	126
RASGRP2	-0.089	0.1	-10000	0	-0.19	186	186
RASGRP1	-0.22	0.34	-10000	0	-0.58	164	164
HLA-A	0.012	0.042	-10000	0	-0.55	2	2
RASSF5	-0.054	0.19	-10000	0	-0.54	48	48
RAP1A/GTP/RAPL	-0.02	0.12	-10000	0	-0.32	48	48
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	-0.042	0.095	-10000	0	-0.14	161	161
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.13	0.14	-10000	0	-0.29	155	155
PRKCA	-0.13	0.16	-10000	0	-0.32	157	157
GRAP2	-0.045	0.18	-10000	0	-0.54	42	42
mol:IP3	-0.23	0.27	0.15	7	-0.52	161	168
EntrezGene:6957	-0.003	0.006	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.59	0.78	-10000	0	-1.4	156	156
ORAI1	0.016	0.04	-10000	0	-0.38	1	1
CSK	-0.42	0.57	-10000	0	-1	160	160
B7 family/CD28	-0.45	0.61	-10000	0	-1.1	160	160
CHUK	0.019	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.54	0.71	-10000	0	-1.3	160	160
PTPN6	-0.46	0.61	-10000	0	-1.1	158	158
VAV1	-0.42	0.57	-10000	0	-1	160	160
Monovalent TCR/CD3	-0.45	0.59	-10000	0	-1	168	168
CBL	0.019	0	-10000	0	-10000	0	0
LCK	-0.5	0.67	-10000	0	-1.2	161	161
PAG1	-0.42	0.57	-10000	0	-1	160	160
RAP1A	0.019	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.55	0.72	-10000	0	-1.3	162	162
CD80	-0.099	0.23	-10000	0	-0.54	76	76
CD86	-0.053	0.19	-10000	0	-0.54	46	46
PDK1/CARD11/BCL10/MALT1	-0.16	0.18	-10000	0	-0.35	158	158
HRAS	0.019	0	-10000	0	-10000	0	0
GO:0035030	-0.32	0.44	-10000	0	-0.81	160	160
CD8A	-0.19	0.27	-10000	0	-0.55	133	133
CD8B	-0.19	0.27	-10000	0	-0.55	136	136
PTPRC	-0.18	0.27	-10000	0	-0.54	131	131
PDK1/PKC theta	-0.26	0.4	-10000	0	-0.7	161	161
CSK/PAG1	-0.4	0.55	-10000	0	-1	159	159
SOS1	0.019	0	-10000	0	-10000	0	0
peptide-MHC class I	0.009	0.069	-10000	0	-0.4	10	10
GRAP2/SLP76	-0.37	0.51	-10000	0	-0.92	162	162
STIM1	0.009	0.018	-10000	0	-10000	0	0
RAS family/GTP	-0.044	0.13	-10000	0	-0.19	151	151
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.58	0.76	-10000	0	-1.4	162	162
mol:DAG	-0.21	0.23	-10000	0	-0.46	162	162
RAP1A/GDP	-0.016	0.042	-10000	0	-0.064	134	134
PLCG1	0.019	0	-10000	0	-10000	0	0
CD247	-0.18	0.27	-10000	0	-0.54	128	128
cytotoxic T cell degranulation	-0.46	0.63	-10000	0	-1.2	146	146
RAP1A/GTP	-0.035	0.033	-10000	0	-0.067	186	186
mol:PI-3-4-5-P3	-0.26	0.38	-10000	0	-0.67	162	162
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.32	0.37	-10000	0	-0.72	161	161
NRAS	0.019	0	-10000	0	-10000	0	0
ZAP70	-0.17	0.26	-10000	0	-0.54	126	126
GRB2/SOS1	0.028	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.32	0.37	-10000	0	-0.72	162	162
MALT1	0.017	0.029	-10000	0	-0.54	1	1
TRAF6	0.019	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.25	0.35	-10000	0	-0.66	148	148
CARD11	-0.14	0.25	-10000	0	-0.54	108	108
PRKCB	-0.17	0.21	-10000	0	-0.38	165	165
PRKCE	-0.13	0.16	-10000	0	-0.31	157	157
PRKCQ	-0.32	0.47	-10000	0	-0.84	162	162
LCP2	-0.016	0.14	-10000	0	-0.54	23	23
BCL10	0.018	0.014	-10000	0	-0.24	1	1
regulation of survival gene product expression	-0.16	0.26	-10000	0	-0.45	162	162
IKK complex	-0.02	0.09	-10000	0	-0.12	152	152
RAS family/GDP	-0.015	0.016	-10000	0	-10000	0	0
MAP3K14	-0.099	0.19	-10000	0	-0.31	156	156
PDPK1	-0.18	0.3	-10000	0	-0.51	159	159
TCR/CD3/MHC I/CD8/Fyn	-0.57	0.74	-10000	0	-1.4	157	157

×

IL23-mediated signaling events

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
CCL2	-0.48	0.67	-9999	-1.2	151	151
IL23A	-0.52	0.71	-9999	-1.3	148	148
NF kappa B1 p50/RelA/I kappa B alpha	-0.6	0.65	-9999	-1.3	154	154
positive regulation of T cell mediated cytotoxicity	-0.62	0.85	-9999	-1.5	157	157
ITGA3	-0.5	0.68	-9999	-1.2	153	153
IL17F	-0.28	0.43	-9999	-0.75	153	153
IL12B	-0.009	0.1	-9999	-0.57	9	9
STAT1 (dimer)	-0.58	0.79	-9999	-1.4	156	156
CD4	-0.5	0.69	-9999	-1.3	150	150
IL23	-0.5	0.68	-9999	-1.3	147	147
IL23R	-0.041	0.11	-9999	-10000	0	0
IL1B	-0.54	0.74	-9999	-1.3	152	152
T-helper cell lineage commitment	0	0	-9999	-10000	0	0
IL24	-0.6	0.74	-9999	-1.3	181	181
TYK2	0.008	0.029	-9999	-10000	0	0
STAT4	-0.12	0.24	-9999	-0.54	92	92
STAT3	0.019	0	-9999	-10000	0	0
IL18RAP	-0.17	0.26	-9999	-0.54	119	119
IL12RB1	-0.14	0.26	-9999	-0.57	97	97
PIK3CA	0.018	0.014	-9999	-0.24	1	1
IL12Rbeta1/TYK2	-0.097	0.2	-9999	-0.43	97	97
IL23R/JAK2	-0.047	0.15	-9999	-0.44	6	6
positive regulation of chronic inflammatory response	-0.62	0.85	-9999	-1.5	157	157
natural killer cell activation	0.005	0.01	-9999	-10000	0	0
JAK2	0	0.085	-9999	-0.53	7	7
PIK3R1	0.019	0	-9999	-10000	0	0
NFKB1	0.017	0.005	-9999	-10000	0	0
RELA	0.017	0.005	-9999	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.46	0.63	-9999	-1.2	150	150
ALOX12B	-0.48	0.67	-9999	-1.2	151	151
CXCL1	-0.5	0.67	-9999	-1.2	155	155
T cell proliferation	-0.62	0.85	-9999	-1.5	157	157
NFKBIA	0.017	0.005	-9999	-10000	0	0
IL17A	-0.2	0.35	-9999	-0.58	140	140
PI3K	-0.54	0.74	-9999	-1.3	154	154
IFNG	-0.05	0.07	-9999	-0.12	174	174
STAT3 (dimer)	-0.57	0.62	-9999	-1.2	153	153
IL18R1	-0.073	0.2	-9999	-0.54	58	58
IL23/IL23R/JAK2/TYK2/SOCS3	-0.28	0.44	-9999	-0.75	146	146
IL18/IL18R	-0.23	0.33	-9999	-0.58	151	151
macrophage activation	-0.023	0.02	-9999	-0.045	155	155
TNF	-0.57	0.77	-9999	-1.4	153	153
STAT3/STAT4	-0.57	0.77	-9999	-1.4	158	158
STAT4 (dimer)	-0.62	0.82	-9999	-1.5	160	160
IL18	-0.14	0.25	-9999	-0.54	99	99
IL19	-0.48	0.66	-9999	-1.2	151	151
STAT5A (dimer)	-0.58	0.79	-9999	-1.4	156	156
STAT1	0.016	0.041	-9999	-0.54	2	2
SOCS3	0.014	0.05	-9999	-0.54	3	3
CXCL9	-0.65	0.81	-9999	-1.5	172	172
MPO	-0.51	0.7	-9999	-1.3	158	158
positive regulation of humoral immune response	-0.62	0.85	-9999	-1.5	157	157
IL23/IL23R/JAK2/TYK2	-0.74	1.1	-9999	-1.8	156	156
IL6	-0.5	0.69	-9999	-1.2	155	155
STAT5A	0.017	0.029	-9999	-0.54	1	1
IL2	0.002	0.021	-9999	-0.24	1	1
positive regulation of tyrosine phosphorylation of STAT protein	0.005	0.01	-9999	-10000	0	0
CD3E	-0.6	0.79	-9999	-1.5	156	156
keratinocyte proliferation	-0.62	0.85	-9999	-1.5	157	157
NOS2	-0.48	0.67	-9999	-1.2	151	151

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0.15	0.2	0.39	148	-10000	0	148
KIRREL	-0.004	0.047	-10000	0	-0.54	2	2
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.15	0.2	-10000	0	-0.39	148	148
PLCG1	0.019	0	-10000	0	-10000	0	0
ARRB2	0.019	0	-10000	0	-10000	0	0
WASL	0.019	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.096	0.15	-10000	0	-0.28	149	149
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.084	0.14	-10000	0	-0.26	148	148
FYN	-0.096	0.14	-10000	0	-0.26	148	148
mol:Ca2+	-0.095	0.15	-10000	0	-0.27	148	148
mol:DAG	-0.095	0.15	-10000	0	-0.28	148	148
NPHS2	-0.019	0.026	-10000	0	-10000	0	0
mol:IP3	-0.095	0.15	-10000	0	-0.28	148	148
regulation of endocytosis	-0.079	0.14	-10000	0	-0.24	148	148
Nephrin/NEPH1/podocin/Cholesterol	-0.1	0.15	-10000	0	-0.28	148	148
establishment of cell polarity	-0.15	0.2	-10000	0	-0.39	148	148
Nephrin/NEPH1/podocin/NCK1-2	-0.076	0.14	-10000	0	-0.24	148	148
Nephrin/NEPH1/beta Arrestin2	-0.079	0.14	-10000	0	-0.25	148	148
NPHS1	-0.21	0.27	-10000	0	-0.54	146	146
Nephrin/NEPH1/podocin	-0.096	0.14	-10000	0	-0.27	148	148
TJP1	0.019	0	-10000	0	-10000	0	0
NCK1	0.019	0	-10000	0	-10000	0	0
NCK2	0.019	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.095	0.15	-10000	0	-0.28	148	148
CD2AP	0.017	0.029	-10000	0	-0.54	1	1
Nephrin/NEPH1/podocin/GRB2	-0.095	0.15	-10000	0	-0.28	148	148
GRB2	0.019	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.098	0.14	-10000	0	-0.26	148	148
cytoskeleton organization	-0.1	0.17	-10000	0	-0.31	148	148
Nephrin/NEPH1	-0.1	0.14	-10000	0	-0.27	148	148
Nephrin/NEPH1/ZO-1	-0.1	0.16	-10000	0	-0.3	148	148

×

IL12-mediated signaling events

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
IL12/IL12R/TYK2/JAK2/SOCS1	-0.12	0.27	-10000	0	-0.48	106	106
TBX21	-0.47	0.81	-10000	0	-1.5	132	132
B2M	0.008	0.082	-10000	0	-0.54	8	8
TYK2	0.013	0.03	-10000	0	-10000	0	0
IL12RB1	-0.13	0.27	-10000	0	-0.57	97	97
GADD45B	-0.37	0.67	-10000	0	-1.2	126	126
IL12RB2	-0.057	0.13	-10000	0	-0.26	95	95
GADD45G	-0.4	0.71	-10000	0	-1.3	131	131
natural killer cell activation	-0.002	0.029	-10000	0	-10000	0	0
RELB	0.019	0	-10000	0	-10000	0	0
RELA	0.019	0	-10000	0	-10000	0	0
IL18	-0.13	0.25	-10000	0	-0.55	99	99
IL2RA	-0.12	0.24	-10000	0	-0.54	93	93
IFNG	-0.18	0.26	-10000	0	-0.54	128	128
STAT3 (dimer)	-0.3	0.57	-10000	0	-1	134	134
HLA-DRB5	-0.015	0.13	-10000	0	-0.5	24	24
FASLG	-0.5	0.83	-10000	0	-1.5	137	137
NF kappa B2 p52/RelB	-0.51	0.68	-10000	0	-1.4	134	134
CD4	-0.034	0.16	-10000	0	-0.54	35	35
SOCS1	-0.01	0.12	-10000	0	-0.54	19	19
EntrezGene:6955	0.002	0.003	-10000	0	-10000	0	0
CD3D	-0.21	0.28	-10000	0	-0.54	154	154
CD3E	-0.19	0.27	-10000	0	-0.54	136	136
CD3G	-0.17	0.26	-10000	0	-0.54	126	126
IL12Rbeta2/JAK2	-0.034	0.11	-10000	0	-0.28	38	38
CCL3	-0.41	0.73	-10000	0	-1.4	128	128
CCL4	-0.45	0.79	-10000	0	-1.5	128	128
HLA-A	0.017	0.041	-10000	0	-0.54	2	2
IL18/IL18R	-0.19	0.36	-10000	0	-0.58	151	151
NOS2	-0.42	0.75	-10000	0	-1.4	129	129
IL12/IL12R/TYK2/JAK2/SPHK2	-0.098	0.24	-10000	0	-0.43	104	104
IL1R1	-0.4	0.72	-10000	0	-1.3	129	129
IL4	0.004	0.031	-10000	0	-0.27	1	1
JAK2	0.004	0.081	-10000	0	-0.52	7	7
EntrezGene:6957	0.002	0.003	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.6	0.83	-10000	0	-1.5	155	155
RAB7A	-0.24	0.52	-10000	0	-0.93	120	120
lysosomal transport	-0.22	0.48	-10000	0	-0.86	122	122
FOS	-0.38	0.64	-10000	0	-1.2	132	132
STAT4 (dimer)	-0.39	0.7	-10000	0	-1.2	136	136
STAT5A (dimer)	-0.56	0.69	-10000	0	-1.3	153	153
GZMA	-0.48	0.82	-10000	0	-1.5	130	130
GZMB	-0.5	0.82	-10000	0	-1.5	140	140
HLX	0.017	0.019	-10000	0	-0.24	2	2
LCK	-0.55	0.9	-10000	0	-1.6	143	143
TCR/CD3/MHC II/CD4	-0.46	0.66	-10000	0	-1.2	146	146
IL2/IL2R	-0.19	0.32	-10000	0	-0.56	138	138
MAPK14	-0.38	0.7	-10000	0	-1.2	134	134
CCR5	-0.4	0.72	-10000	0	-1.3	130	130
IL1B	-0.045	0.17	-10000	0	-0.5	43	43
STAT6	-0.043	0.16	-10000	0	-0.25	113	113
STAT4	-0.12	0.24	-10000	0	-0.54	92	92
STAT3	0.019	0	-10000	0	-10000	0	0
STAT1	0.016	0.041	-10000	0	-0.54	2	2
NFKB1	0.019	0	-10000	0	-10000	0	0
NFKB2	0.019	0	-10000	0	-10000	0	0
IL12B	-0.001	0.094	-10000	0	-0.55	9	9
CD8A	-0.18	0.27	-10000	0	-0.54	133	133
CD8B	-0.19	0.27	-10000	0	-0.54	136	136
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.11	0.26	0.48	106	-10000	0	106
IL2RB	-0.083	0.22	-10000	0	-0.54	67	67
proteasomal ubiquitin-dependent protein catabolic process	-0.31	0.6	-10000	0	-1	136	136
IL2RG	-0.15	0.26	-10000	0	-0.54	112	112
IL12	-0.011	0.13	-10000	0	-0.42	29	29
STAT5A	0.017	0.029	-10000	0	-0.54	1	1
CD247	-0.17	0.27	-10000	0	-0.54	128	128
IL2	0.005	0.016	-10000	0	-0.24	1	1
SPHK2	0.019	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.019	0.14	-10000	0	-0.55	21	21
IL12/IL12R/TYK2/JAK2	-0.68	1.2	-10000	0	-2.1	134	134
MAP2K3	-0.39	0.72	-10000	0	-1.3	135	135
RIPK2	0.019	0	-10000	0	-10000	0	0
MAP2K6	-0.4	0.72	-10000	0	-1.3	135	135
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.1	0.23	-10000	0	-0.54	81	81
IL18RAP	-0.16	0.27	-10000	0	-0.54	119	119
IL12Rbeta1/TYK2	-0.088	0.21	-10000	0	-0.43	97	97
EOMES	-0.15	0.4	-10000	0	-1.4	32	32
STAT1 (dimer)	-0.38	0.59	-10000	0	-1	161	161
T cell proliferation	-0.22	0.46	-10000	0	-0.79	138	138
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.067	0.21	-10000	0	-0.55	58	58
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.36	0.42	-10000	0	-0.86	141	141
ATF2	-0.31	0.61	-10000	0	-1.1	131	131

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	-0.12	0.26	-10000	0	-0.49	114	114
ACTA1	-0.16	0.31	0.2	7	-0.59	114	121
NUMA1	-0.12	0.26	-10000	0	-0.49	114	114
SPTAN1	-0.16	0.31	0.23	1	-0.59	114	115
LIMK1	-0.16	0.31	0.23	1	-0.59	114	115
BIRC3	-0.18	0.26	-10000	0	-0.54	128	128
BIRC2	0.013	0.052	-10000	0	-0.46	4	4
BAX	0.019	0	-10000	0	-10000	0	0
CASP10	-0.18	0.29	-10000	0	-0.54	136	136
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.019	0	-10000	0	-10000	0	0
PTK2	-0.12	0.26	0.19	1	-0.49	114	115
DIABLO	0.019	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.15	0.3	0.23	1	-0.57	114	115
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.018	0.014	-10000	0	-0.24	1	1
GSN	-0.16	0.31	0.24	1	-0.59	114	115
MADD	0.019	0	-10000	0	-10000	0	0
TFAP2A	-0.16	0.34	-10000	0	-0.8	80	80
BID	-0.09	0.16	-10000	0	-0.29	136	136
MAP3K1	-0.036	0.1	-10000	0	-0.21	37	37
TRADD	0.019	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.029	0.001	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.18	0.35	0.23	1	-0.65	116	117
CASP9	0.019	0	-10000	0	-10000	0	0
DNA repair	-0.019	0.08	0.15	31	-0.18	43	74
neuron apoptosis	-0.003	0.091	-10000	0	-0.65	5	5
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.14	0.3	0.22	1	-0.56	114	115
APAF1	0.019	0	-10000	0	-10000	0	0
CASP6	-0.084	0.19	-10000	0	-0.42	74	74
TRAF2	0.019	0	-10000	0	-10000	0	0
ICAD/CAD	-0.14	0.3	0.23	1	-0.56	114	115
CASP7	0.11	0.15	0.31	128	-10000	0	128
KRT18	-0.094	0.24	-10000	0	-0.69	48	48
apoptosis	-0.1	0.25	0.22	35	-0.45	113	148
DFFA	-0.16	0.31	0.23	1	-0.59	114	115
DFFB	-0.16	0.31	0.23	1	-0.59	114	115
PARP1	0.019	0.081	0.18	43	-0.15	31	74
actin filament polymerization	0.14	0.29	0.54	114	-0.23	1	115
TNF	-0.095	0.22	-10000	0	-0.54	75	75
CYCS	-0.063	0.11	-10000	0	-0.22	116	116
SATB1	-0.091	0.21	-10000	0	-0.49	56	56
SLK	-0.16	0.31	0.23	1	-0.59	114	115
p15 BID/BAX	-0.073	0.14	-10000	0	-0.3	94	94
CASP2	-0.054	0.14	-10000	0	-0.34	53	53
JNK cascade	0.035	0.1	0.21	37	-10000	0	37
CASP3	-0.17	0.33	0.21	7	-0.62	114	121
LMNB2	-0.053	0.15	-10000	0	-0.32	64	64
RIPK1	0.019	0	-10000	0	-10000	0	0
CASP4	0.013	0.058	-10000	0	-0.54	4	4
Mammalian IAPs/DIABLO	-0.069	0.16	-10000	0	-0.29	128	128
negative regulation of DNA binding	-0.16	0.34	-10000	0	-0.78	80	80
stress fiber formation	-0.15	0.3	0.23	1	-0.57	114	115
GZMB	-0.21	0.32	-10000	0	-0.6	136	136
CASP1	-0.003	0.099	-10000	0	-0.37	22	22
LMNB1	-0.053	0.15	-10000	0	-0.33	62	62
APP	-0.003	0.092	-10000	0	-0.66	5	5
TNFRSF1A	0.019	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.011	0.03	-10000	0	-0.39	2	2
VIM	-0.099	0.25	0.21	41	-0.44	113	154
LMNA	-0.054	0.15	-10000	0	-0.33	61	61
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.064	0.15	-10000	0	-0.37	53	53
LRDD	0.017	0.029	-10000	0	-0.54	1	1
SREBF1	-0.16	0.31	0.23	1	-0.59	114	115
APAF-1/Caspase 9	0.03	0.073	0.42	3	-10000	0	3
nuclear fragmentation during apoptosis	-0.12	0.26	-10000	0	-0.48	114	114
CFL2	-0.14	0.3	0.23	1	-0.55	114	115
GAS2	-0.17	0.32	0.23	1	-0.6	120	121
positive regulation of apoptosis	-0.048	0.15	-10000	0	-0.32	61	61
PRF1	-0.15	0.25	-10000	0	-0.54	109	109

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.066	0.086	0.19	116	-10000	0	116
RFC1	0.066	0.086	0.19	116	-10000	0	116
PRKDC	0.066	0.086	0.19	116	-10000	0	116
RIPK1	0.019	0.002	-10000	0	-10000	0	0
CASP7	0.064	0.11	0.25	54	-0.26	1	55
FASLG/FAS/FADD/FAF1	-0.007	0.15	0.22	57	-0.28	64	121
MAP2K4	-0.018	0.16	-10000	0	-0.38	24	24
mol:ceramide	-0.073	0.19	-10000	0	-0.33	120	120
GSN	0.066	0.085	0.19	115	-10000	0	115
FASLG/FAS/FADD/FAF1/Caspase 8	-0.04	0.17	-10000	0	-0.32	66	66
FAS	0.007	0.081	-10000	0	-0.54	8	8
BID	0.1	0.13	0.3	116	-10000	0	116
MAP3K1	0.033	0.11	0.21	54	-0.27	9	63
MAP3K7	0.019	0.002	-10000	0	-10000	0	0
RB1	0.065	0.088	0.19	116	-0.31	1	117
CFLAR	0.019	0.002	-10000	0	-10000	0	0
HGF/MET	-0.004	0.11	-10000	0	-0.34	31	31
ARHGDIB	0.034	0.13	0.19	106	-0.31	26	132
FADD	0.018	0.014	-10000	0	-0.24	1	1
actin filament polymerization	-0.065	0.085	-10000	0	-0.19	115	115
NFKB1	-0.015	0.065	-10000	0	-0.27	8	8
MAPK8	-0.013	0.16	-10000	0	-0.44	23	23
DFFA	0.066	0.086	0.19	116	-10000	0	116
DNA fragmentation during apoptosis	0.066	0.085	0.19	116	-10000	0	116
FAS/FADD/MET	0.004	0.1	-10000	0	-0.33	29	29
CFLAR/RIP1	0.027	0.005	-10000	0	-10000	0	0
FAIM3	-0.16	0.26	-10000	0	-0.54	118	118
FAF1	0.019	0.005	-10000	0	-10000	0	0
PARP1	0.066	0.086	0.19	116	-10000	0	116
DFFB	0.066	0.086	0.19	116	-10000	0	116
CHUK	-0.006	0.06	-10000	0	-0.26	2	2
FASLG	-0.16	0.26	-10000	0	-0.54	120	120
FAS/FADD	0.019	0.061	-10000	0	-0.38	8	8
HGF	0	0.085	-10000	0	-0.34	19	19
LMNA	0.066	0.077	0.18	109	-10000	0	109
CASP6	0.066	0.086	0.19	116	-10000	0	116
CASP10	0.008	0.076	-10000	0	-0.54	7	7
CASP3	0.069	0.1	0.22	116	-10000	0	116
PTPN13	0.011	0.062	-10000	0	-0.41	7	7
CASP8	0.12	0.18	0.38	116	-10000	0	116
IL6	-0.044	0.27	-10000	0	-1.2	16	16
MET	-0.024	0.14	-10000	0	-0.43	35	35
ICAD/CAD	0.067	0.077	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 10	-0.075	0.19	-10000	0	-0.33	120	120
activation of caspase activity by cytochrome c	0.1	0.13	0.3	116	-10000	0	116
PAK2	0.066	0.086	0.19	114	-10000	0	114
BCL2	0.019	0	-10000	0	-10000	0	0

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	-0.089	0.23	-10000	0	-0.55	68	68
NFATC2	-0.16	0.39	-10000	0	-0.68	109	109
NFATC3	-0.006	0.065	-10000	0	-0.23	4	4
CD40LG	-0.51	0.55	-10000	0	-1	182	182
ITCH	0.004	0.065	-10000	0	-10000	0	0
CBLB	0.004	0.067	-10000	0	-0.35	1	1
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.5	0.7	-10000	0	-1.3	142	142
JUNB	0.017	0.019	-10000	0	-0.24	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.01	0.079	-10000	0	-0.28	2	2
T cell anergy	-0.04	0.099	-10000	0	-0.31	8	8
TLE4	-0.13	0.35	-10000	0	-0.74	68	68
Jun/NFAT1-c-4/p21SNFT	-0.28	0.46	-10000	0	-0.86	108	108
AP-1/NFAT1-c-4	-0.44	0.59	-10000	0	-1.1	144	144
IKZF1	-0.22	0.46	-10000	0	-0.91	104	104
T-helper 2 cell differentiation	-0.24	0.42	-10000	0	-0.91	95	95
AP-1/NFAT1	-0.15	0.29	-10000	0	-0.52	105	105
CALM1	0.001	0.046	-10000	0	-10000	0	0
EGR2	-0.15	0.33	-10000	0	-0.8	39	39
EGR3	-0.17	0.39	-10000	0	-1	35	35
NFAT1/FOXP3	-0.19	0.41	-10000	0	-0.74	113	113
EGR1	-0.004	0.073	-10000	0	-0.25	30	30
JUN	-0.03	0.085	-10000	0	-0.28	36	36
EGR4	0	0.061	-10000	0	-0.24	21	21
mol:Ca2+	-0.018	0.047	-10000	0	-0.17	2	2
GBP3	-0.14	0.36	-10000	0	-0.76	76	76
FOSL1	-0.014	0.12	-10000	0	-0.45	26	26
NFAT1-c-4/MAF/IRF4	-0.21	0.42	-10000	0	-0.85	82	82
DGKA	-0.12	0.34	-10000	0	-0.71	69	69
CREM	0.018	0.001	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.21	0.43	-10000	0	-0.89	75	75
CTLA4	-0.21	0.43	-10000	0	-0.81	109	109
NFAT1-c-4 (dimer)/EGR1	-0.23	0.44	-10000	0	-0.88	87	87
NFAT1-c-4 (dimer)/EGR4	-0.22	0.44	-10000	0	-0.89	86	86
FOS	-0.012	0.053	-10000	0	-0.27	11	11
IFNG	-0.62	0.76	-10000	0	-1.4	177	177
T cell activation	-0.14	0.27	-10000	0	-0.74	33	33
MAF	0.019	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	0.12	0.31	1.1	18	-10000	0	18
TNF	-0.27	0.48	-10000	0	-0.99	99	99
FASLG	-0.58	0.85	-10000	0	-1.7	127	127
TBX21	-0.16	0.25	-10000	0	-0.56	104	104
BATF3	0.007	0.081	-10000	0	-0.54	8	8
PRKCQ	-0.17	0.27	-10000	0	-0.56	116	116
PTPN1	-0.11	0.3	-10000	0	-0.62	69	69
NFAT1-c-4/ICER1	-0.21	0.42	-10000	0	-0.87	77	77
GATA3	-0.1	0.23	-10000	0	-0.54	80	80
T-helper 1 cell differentiation	-0.59	0.72	-10000	0	-1.3	177	177
IL2RA	-0.45	0.64	-10000	0	-1.2	143	143
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.11	0.3	-10000	0	-0.66	62	62
E2F1	0.026	0.006	-10000	0	-10000	0	0
PPARG	0.011	0.064	-10000	0	-0.54	5	5
SLC3A2	-0.11	0.3	-10000	0	-0.65	64	64
IRF4	-0.031	0.16	-10000	0	-0.54	33	33
PTGS2	-0.4	0.49	-10000	0	-0.93	145	145
CSF2	-0.39	0.48	-10000	0	-0.91	144	144
JunB/Fra1/NFAT1-c-4	-0.2	0.41	-10000	0	-0.89	70	70
IL4	-0.26	0.45	-10000	0	-0.96	95	95
IL5	-0.39	0.48	-10000	0	-0.92	144	144
IL2	-0.14	0.27	-10000	0	-0.76	32	32
IL3	-0.067	0.06	-10000	0	-10000	0	0
RNF128	-0.049	0.13	-10000	0	-0.48	2	2
NFATC1	-0.12	0.31	-10000	0	-1.1	18	18
CDK4	0.1	0.21	0.66	13	-10000	0	13
PTPRK	-0.11	0.3	-10000	0	-0.63	69	69
IL8	-0.41	0.48	-10000	0	-0.94	145	145
POU2F1	0.019	0	-10000	0	-10000	0	0

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.064	0.16	-9999	-0.32	101	101
E-cadherin/beta catenin	-0.085	0.18	-9999	-0.38	101	101
CTNNB1	0.019	0	-9999	-10000	0	0
JUP	0.011	0.045	-9999	-0.24	11	11
CDH1	-0.13	0.25	-9999	-0.54	101	101

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.027	0.072	-9999	-0.4	9	9
NFATC2	-0.043	0.1	-9999	-0.36	26	26
NFATC3	-0.017	0.042	-9999	-10000	0	0
CD40LG	-0.43	0.44	-9999	-0.75	221	221
PTGS2	-0.32	0.37	-9999	-0.65	183	183
JUNB	0.017	0.019	-9999	-0.24	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.012	0.027	-9999	-10000	0	0
CaM/Ca2+	-0.012	0.026	-9999	-10000	0	0
CALM1	0.005	0.016	-9999	-10000	0	0
JUN	-0.022	0.081	-9999	-0.26	36	36
mol:Ca2+	-0.017	0.017	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.004	0.01	-9999	-10000	0	0
FOSL1	-0.014	0.12	-9999	-0.45	26	26
CREM	0.019	0	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.16	0.22	-9999	-0.41	125	125
FOS	-0.003	0.049	-9999	-0.26	11	11
IFNG	-0.39	0.43	-9999	-0.75	191	191
AP-1/NFAT1-c-4	-0.38	0.46	-9999	-0.78	182	182
FASLG	-0.38	0.44	-9999	-0.77	179	179
NFAT1-c-4/ICER1	-0.082	0.15	-9999	-0.43	31	31
IL2RA	-0.36	0.42	-9999	-0.74	178	178
FKBP12/FK506	0.014	0	-9999	-10000	0	0
CSF2	-0.31	0.36	-9999	-0.64	177	177
JunB/Fra1/NFAT1-c-4	-0.087	0.16	-9999	-0.4	46	46
IL4	-0.31	0.36	-9999	-0.64	176	176
IL2	-0.013	0.021	-9999	-10000	0	0
IL3	-0.029	0.026	-9999	-10000	0	0
FKBP1A	0.019	0	-9999	-10000	0	0
BATF3	0.007	0.081	-9999	-0.54	8	8
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.019	0	-9999	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.1	0.27	-9999	-0.49	100	100
MAP4K1	-0.081	0.21	-9999	-0.54	66	66
MAP3K8	-0.003	0.11	-9999	-0.52	15	15
PRKCB	-0.15	0.26	-9999	-0.54	110	110
DBNL	0.019	0	-9999	-10000	0	0
CRKL	0.018	0.014	-9999	-0.24	1	1
MAP3K1	-0.073	0.24	-9999	-0.6	53	53
JUN	-0.2	0.35	-9999	-0.71	110	110
MAP3K7	-0.073	0.24	-9999	-0.6	53	53
GRAP2	-0.045	0.18	-9999	-0.54	42	42
CRK	0.019	0	-9999	-10000	0	0
MAP2K4	-0.07	0.25	-9999	-0.59	57	57
LAT	-0.049	0.18	-9999	-0.54	45	45
LCP2	-0.016	0.14	-9999	-0.54	23	23
MAPK8	-0.2	0.37	-9999	-0.74	110	110
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.084	0.26	-9999	-0.52	74	74
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.086	0.26	-9999	-0.46	100	100

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.15	0.33	-9999	-0.66	97	97
MAP3K8	-0.003	0.11	-9999	-0.52	15	15
FOS	-0.17	0.34	-9999	-0.69	98	98
PRKCA	0.014	0.044	-9999	-0.28	7	7
PTPN7	-0.12	0.24	-9999	-0.54	95	95
HRAS	0.019	0	-9999	-10000	0	0
PRKCB	-0.15	0.26	-9999	-0.54	110	110
NRAS	0.019	0	-9999	-10000	0	0
RAS family/GTP	0.037	0.008	-9999	-10000	0	0
MAPK3	-0.16	0.33	-9999	-0.69	96	96
MAP2K1	-0.093	0.22	-9999	-0.42	110	110
ELK1	0.02	0.002	-9999	-10000	0	0
BRAF	-0.096	0.21	-9999	-0.41	110	110
mol:GTP	0	0	-9999	-0.003	8	8
MAPK1	-0.16	0.33	-9999	-0.7	95	95
RAF1	-0.094	0.2	-9999	-0.4	110	110
KRAS	0.018	0.014	-9999	-0.24	1	1

×

IL27-mediated signaling events

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
TGFB1	0.016	0.041	-10000	0	-0.54	2	2
CD4-positive alpha-beta T cell lineage commitment	0	0.001	-10000	0	-10000	0	0
cytokine production during immune response	0.16	0.31	0.63	80	-10000	0	80
IL27/IL27R/JAK1	-0.17	0.35	-10000	0	-0.72	72	72
TBX21	-0.22	0.32	-10000	0	-0.64	119	119
IL12B	-0.004	0.085	-10000	0	-0.54	9	9
IL12A	-0.014	0.092	-10000	0	-0.38	21	21
IL6ST	-0.001	0.082	-10000	0	-0.55	8	8
IL27RA/JAK1	-0.07	0.3	-10000	0	-1.3	20	20
IL27	-0.051	0.17	-10000	0	-0.55	39	39
TYK2	0.011	0.013	-10000	0	-10000	0	0
T-helper cell lineage commitment	0.003	0.07	-10000	0	-0.67	1	1
T-helper 2 cell differentiation	0.16	0.31	0.63	80	-10000	0	80
T cell proliferation during immune response	0.16	0.31	0.63	80	-10000	0	80
MAPKKK cascade	-0.16	0.31	-10000	0	-0.63	80	80
STAT3	0.019	0	-10000	0	-10000	0	0
STAT2	0.019	0	-10000	0	-10000	0	0
STAT1	0.015	0.041	-10000	0	-0.54	2	2
IL12RB1	-0.13	0.24	-10000	0	-0.54	97	97
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.19	0.27	-10000	0	-0.55	107	107
IL27/IL27R/JAK2/TYK2	-0.17	0.32	-10000	0	-0.64	80	80
positive regulation of T cell mediated cytotoxicity	-0.16	0.31	-10000	0	-0.63	80	80
STAT1 (dimer)	-0.26	0.36	0.4	2	-0.83	82	84
JAK2	0.006	0.073	-10000	0	-0.5	7	7
JAK1	0.018	0.002	-10000	0	-10000	0	0
STAT2 (dimer)	-0.15	0.3	-10000	0	-0.6	80	80
T cell proliferation	-0.16	0.3	-10000	0	-0.6	85	85
IL12/IL12R/TYK2/JAK2	-0.17	0.28	-10000	0	-0.61	75	75
IL17A	0.003	0.07	-10000	0	-0.67	1	1
mast cell activation	0.16	0.31	0.63	80	-10000	0	80
IFNG	-0.046	0.067	-10000	0	-0.12	144	144
T cell differentiation	-0.01	0.011	0.012	1	-0.023	140	141
STAT3 (dimer)	-0.15	0.3	-10000	0	-0.6	80	80
STAT5A (dimer)	-0.15	0.3	-10000	0	-0.6	81	81
STAT4 (dimer)	-0.22	0.35	-10000	0	-0.65	115	115
STAT4	-0.12	0.24	-10000	0	-0.54	92	92
T cell activation	-0.003	0.032	0.13	20	-10000	0	20
IL27R/JAK2/TYK2	-0.08	0.3	-10000	0	-1.2	23	23
GATA3	-0.27	0.57	-10000	0	-1.3	80	80
IL18	-0.098	0.18	-10000	0	-0.39	99	99
positive regulation of mast cell cytokine production	-0.15	0.28	-10000	0	-0.58	80	80
IL27/EBI3	-0.11	0.23	-10000	0	-0.47	98	98
IL27RA	-0.083	0.32	-10000	0	-1.4	20	20
IL6	-0.008	0.11	-10000	0	-0.43	22	22
STAT5A	0.017	0.029	-10000	0	-0.54	1	1
monocyte differentiation	-0.002	0.003	-10000	0	-10000	0	0
IL2	0.031	0.12	0.5	20	-10000	0	20
IL1B	-0.03	0.12	-10000	0	-0.34	43	43
EBI3	-0.11	0.23	-10000	0	-0.55	81	81
TNF	-0.071	0.16	-10000	0	-0.39	75	75

×

S1P4 pathway

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
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.094	0.13	-9999	-0.24	156	156
CDC42/GTP	-0.088	0.14	-9999	-0.27	121	121
PLCG1	-0.093	0.14	-9999	-0.28	121	121
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.019	0	-9999	-10000	0	0
GNAI3	0.019	0	-9999	-10000	0	0
G12/G13	0.028	0	-9999	-10000	0	0
cell migration	-0.087	0.14	-9999	-0.26	121	121
S1PR5	0.008	0.052	-9999	-0.24	15	15
S1PR4	-0.16	0.26	-9999	-0.54	121	121
MAPK3	-0.093	0.14	-9999	-0.28	121	121
MAPK1	-0.093	0.14	-9999	-0.28	121	121
S1P/S1P5/Gi	-0.017	0.065	-9999	-0.24	5	5
GNAI1	0.005	0.058	-9999	-0.24	19	19
CDC42/GDP	0.014	0	-9999	-10000	0	0
S1P/S1P5/G12	0.019	0.03	-9999	-10000	0	0
RHOA	-0.063	0.14	-9999	-0.26	121	121
S1P/S1P4/Gi	-0.11	0.15	-9999	-0.3	121	121
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.016	0.094	-9999	-0.26	46	46
S1P/S1P4/G12/G13	-0.071	0.15	-9999	-0.29	121	121
GNA12	0.019	0	-9999	-10000	0	0
GNA13	0.019	0	-9999	-10000	0	0
CDC42	0.019	0	-9999	-10000	0	0

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	-0.037	0.099	-10000	0	-0.28	26	26
fibroblast growth factor receptor signaling pathway	-0.037	0.099	-10000	0	-0.27	26	26
LAMA1	-0.2	0.1	-10000	0	-0.24	302	302
PRNP	0.017	0.029	-10000	0	-0.54	1	1
GPC1/SLIT2	-0.051	0.11	-10000	0	-0.33	21	21
SMAD2	-0.007	0.062	-10000	0	-10000	0	0
GPC1/PrPc/Cu2+	-0.025	0.072	-10000	0	-0.32	1	1
GPC1/Laminin alpha1	-0.17	0.1	-10000	0	-0.3	105	105
TDGF1	-0.088	0.21	-10000	0	-0.54	64	64
CRIPTO/GPC1	-0.11	0.16	-10000	0	-0.42	64	64
APP/GPC1	-0.035	0.09	-10000	0	-0.38	3	3
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.081	0.14	-10000	0	-0.35	64	64
FLT1	0.018	0.014	-10000	0	-0.24	1	1
GPC1/TGFB/TGFBR1/TGFBR2	-0.013	0.072	-10000	0	-10000	0	0
SERPINC1	0.006	0.045	-10000	0	-0.24	11	11
FYN	-0.081	0.14	-10000	0	-0.35	64	64
FGR	-0.11	0.17	-10000	0	-0.37	95	95
positive regulation of MAPKKK cascade	-0.3	0.28	-10000	0	-0.51	196	196
SLIT2	-0.012	0.094	-10000	0	-0.27	38	38
GPC1/NRG	-0.044	0.1	-10000	0	-0.33	16	16
NRG1	-0.001	0.073	-10000	0	-0.29	20	20
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.021	0.082	-10000	0	-0.25	12	12
LYN	-0.095	0.15	-10000	0	-0.36	77	77
mol:Spermine	-0.045	0.082	-10000	0	-0.16	122	122
cell growth	-0.037	0.099	-10000	0	-0.27	26	26
BMP signaling pathway	0.068	0.12	0.24	122	-10000	0	122
SRC	-0.081	0.14	-10000	0	-0.35	64	64
TGFBR1	0.019	0	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.062	0.16	-10000	0	-0.32	86	86
GPC1	-0.069	0.12	-10000	0	-0.24	122	122
TGFBR1 (dimer)	0.019	0	-10000	0	-10000	0	0
VEGFA	0.004	0.061	-10000	0	-0.24	21	21
BLK	-0.3	0.21	-10000	0	-0.42	255	255
HCK	-0.11	0.16	-10000	0	-0.36	91	91
FGF2	-0.004	0.08	-10000	0	-0.26	30	30
FGFR1	-0.003	0.072	-10000	0	-0.24	30	30
VEGFR1 homodimer	0.018	0.014	-10000	0	-0.24	1	1
TGFBR2	0.019	0	-10000	0	-10000	0	0
cell death	-0.035	0.09	-10000	0	-0.38	3	3
ATIII/GPC1	-0.04	0.09	-10000	0	-0.3	6	6
PLA2G2A/GPC1	-0.086	0.14	-10000	0	-0.37	44	44
LCK	-0.21	0.22	-10000	0	-0.41	179	179
neuron differentiation	-0.044	0.1	-10000	0	-0.33	16	16
PrPc/Cu2+	0.013	0.021	-10000	0	-0.39	1	1
APP	0.014	0.05	-10000	0	-0.54	3	3
TGFBR2 (dimer)	0.019	0	-10000	0	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0	0.047	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.069	0.11	-9999	-0.3	15	15
JUN	-0.039	0.12	-9999	-0.31	14	14
HRAS	0.019	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.064	0.15	-9999	-0.29	106	106
RAP1A	0.019	0	-9999	-10000	0	0
FRS2	0.017	0.024	-9999	-0.24	3	3
RAP1A/GDP	0.014	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.064	0.15	-9999	-0.28	105	105
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.019	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.019	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.072	0.15	-9999	-0.29	103	103
RHOA	0.019	0	-9999	-10000	0	0
RAP1A/GTP	-0.053	0.13	-9999	-0.25	102	102
GRB7	-0.003	0.067	-9999	-0.24	26	26
RET51/GFRalpha1/GDNF	-0.064	0.15	-9999	-0.28	105	105
MAPKKK cascade	-0.073	0.11	-9999	-0.26	23	23
BCAR1	0.019	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.082	0.15	-9999	-0.3	106	106
lamellipodium assembly	-0.07	0.1	-9999	-0.24	101	101
RET51/GFRalpha1/GDNF/SHC	-0.064	0.15	-9999	-0.28	105	105
PIK3CA	0.018	0.014	-9999	-0.24	1	1
RET9/GFRalpha1/GDNF/SHC	-0.072	0.15	-9999	-0.29	103	103
RET9/GFRalpha1/GDNF/Shank3	-0.072	0.15	-9999	-0.29	103	103
MAPK3	-0.046	0.12	-9999	-0.23	102	102
DOK1	0.019	0	-9999	-10000	0	0
DOK6	-0.011	0.1	-9999	-0.31	33	33
PXN	0.019	0	-9999	-10000	0	0
neurite development	-0.036	0.12	-9999	-0.32	12	12
DOK5	-0.049	0.12	-9999	-0.25	91	91
GFRA1	-0.13	0.24	-9999	-0.52	101	101
MAPK8	-0.037	0.12	-9999	-0.33	4	4
HRAS/GTP	-0.063	0.14	-9999	-0.28	102	102
tube development	-0.061	0.14	-9999	-0.27	103	103
MAPK1	-0.046	0.12	-9999	-0.23	102	102
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.051	0.12	-9999	-0.24	101	101
Rac1/GDP	0.014	0	-9999	-10000	0	0
SRC	0.019	0	-9999	-10000	0	0
PDLIM7	0.019	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.065	0.15	-9999	-0.28	105	105
SHC1	0.019	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.064	0.15	-9999	-0.28	105	105
RET51/GFRalpha1/GDNF/Dok5	-0.098	0.16	-9999	-0.3	121	121
PRKCA	0.013	0.044	-9999	-0.28	7	7
HRAS/GDP	0.014	0	-9999	-10000	0	0
CREB1	-0.052	0.14	-9999	-0.27	101	101
PIK3R1	0.019	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.051	0.12	-9999	-0.24	101	101
RET51/GFRalpha1/GDNF/Grb7	-0.075	0.15	-9999	-0.29	111	111
mol:GDP	0	0	-9999	-10000	0	0
RET	0.014	0.04	-9999	-0.3	5	5
DOK4	0.019	0	-9999	-10000	0	0
JNK cascade	-0.038	0.11	-9999	-0.3	14	14
RET9/GFRalpha1/GDNF/FRS2	-0.073	0.14	-9999	-0.29	103	103
SHANK3	0.017	0.019	-9999	-0.24	2	2
RASA1	0.017	0.029	-9999	-0.54	1	1
NCK1	0.019	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.051	0.12	-9999	-0.24	101	101
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.046	0.12	-9999	-0.23	102	102
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.046	0.12	-9999	-0.23	103	103
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.045	0.12	-9999	-0.23	102	102
PI3K	-0.063	0.18	-9999	-0.34	101	101
SOS1	0.019	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.059	0.14	-9999	-0.27	103	103
GRB10	0.017	0.019	-9999	-0.24	2	2
activation of MAPKK activity	-0.047	0.12	-9999	-0.33	11	11
RET51/GFRalpha1/GDNF/FRS2	-0.065	0.15	-9999	-0.28	106	106
GAB1	0.019	0	-9999	-10000	0	0
IRS1	-0.003	0.072	-9999	-0.24	30	30
IRS2	0.019	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.045	0.12	-9999	-0.23	102	102
RET51/GFRalpha1/GDNF/PKC alpha	-0.067	0.15	-9999	-0.29	108	108
GRB2	0.019	0	-9999	-10000	0	0
PRKACA	0.019	0	-9999	-10000	0	0
GDNF	-0.022	0.11	-9999	-0.3	44	44
RAC1	0.019	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.074	0.15	-9999	-0.3	108	108
Rac1/GTP	-0.082	0.12	-9999	-0.28	101	101
RET9/GFRalpha1/GDNF	-0.091	0.16	-9999	-0.33	103	103
GFRalpha1/GDNF	-0.11	0.18	-9999	-0.39	103	103

×

Wnt 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
Noncanonical Wnts/FZD	-0.048	0.11	-9999	-0.32	31	31
FZD6	-0.01	0.12	-9999	-0.54	19	19
WNT6	0.008	0.052	-9999	-0.24	15	15
WNT4	-0.082	0.13	-9999	-0.24	141	141
FZD3	0.019	0	-9999	-10000	0	0
WNT5A	0	0.091	-9999	-0.37	18	18
WNT11	-0.065	0.12	-9999	-0.24	117	117

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.047	0.17	-9999	-0.46	45	45
alphaM/beta2 Integrin/GPIbA	-0.2	0.25	-9999	-0.4	201	201
alphaM/beta2 Integrin/proMMP-9	-0.086	0.23	-9999	-0.47	86	86
PLAUR	0.013	0.044	-9999	-0.28	7	7
HMGB1	0.011	0.021	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.027	0.16	-9999	-0.44	44	44
AGER	0.01	0.028	-9999	-0.24	2	2
RAP1A	0.019	0	-9999	-10000	0	0
SELPLG	-0.036	0.16	-9999	-0.54	36	36
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.038	0.2	-9999	-0.47	48	48
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.082	0.21	-9999	-0.52	68	68
CYR61	0.012	0.053	-9999	-0.32	8	8
TLN1	0.019	0	-9999	-10000	0	0
Rap1/GTP	-0.11	0.19	-9999	-0.47	61	61
RHOA	0.019	0	-9999	-10000	0	0
P-selectin oligomer	-0.17	0.26	-9999	-0.54	123	123
MYH2	-0.12	0.22	-9999	-0.41	96	96
MST1R	-0.014	0.13	-9999	-0.48	24	24
leukocyte activation during inflammatory response	-0.04	0.14	-9999	-0.4	44	44
APOB	-0.012	0.07	-9999	-0.24	30	30
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.018	0.096	-9999	-0.26	49	49
JAM3	-0.006	0.077	-9999	-0.24	35	35
GP1BA	-0.27	0.28	-9999	-0.54	190	190
alphaM/beta2 Integrin/CTGF	-0.034	0.16	-9999	-0.43	46	46
alphaM/beta2 Integrin	-0.12	0.24	-9999	-0.43	94	94
JAM3 homodimer	-0.006	0.077	-9999	-0.24	35	35
ICAM2	-0.019	0.14	-9999	-0.54	25	25
ICAM1	0.008	0.076	-9999	-0.54	7	7
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.12	0.24	-9999	-0.42	94	94
cell adhesion	-0.2	0.25	-9999	-0.4	201	201
NFKB1	-0.066	0.25	-9999	-0.46	87	87
THY1	0.015	0.043	-9999	-0.44	3	3
RhoA/GDP	0.014	0	-9999	-10000	0	0
Lipoprotein(a)	-0.006	0.038	-9999	-10000	0	0
alphaM/beta2 Integrin/LRP/tPA	-0.018	0.15	-9999	-0.39	46	46
IL6	-0.07	0.26	-9999	-0.48	87	87
ITGB2	-0.057	0.19	-9999	-0.57	44	44
elevation of cytosolic calcium ion concentration	-0.02	0.16	-9999	-0.4	46	46
alphaM/beta2 Integrin/JAM2/JAM3	-0.027	0.16	-9999	-0.42	45	45
JAM2	0.015	0.043	-9999	-0.44	3	3
alphaM/beta2 Integrin/ICAM1	-0.026	0.18	-9999	-0.38	63	63
alphaM/beta2 Integrin/uPA/Plg	-0.027	0.15	-9999	-0.41	44	44
RhoA/GTP	-0.13	0.23	-9999	-0.36	142	142
positive regulation of phagocytosis	-0.099	0.25	-9999	-0.58	63	63
Ron/MSP	0.002	0.096	-9999	-0.38	21	21
alphaM/beta2 Integrin/uPAR/uPA	-0.019	0.16	-9999	-0.4	46	46
alphaM/beta2 Integrin/uPAR	-0.03	0.17	-9999	-0.45	44	44
PLAU	0.012	0.048	-9999	-0.28	9	9
PLAT	0.012	0.051	-9999	-0.33	7	7
actin filament polymerization	-0.11	0.21	-9999	-0.39	96	96
MST1	0.016	0.035	-9999	-0.34	3	3
alphaM/beta2 Integrin/lipoprotein(a)	-0.038	0.15	-9999	-0.4	44	44
TNF	-0.14	0.38	-9999	-0.83	79	79
RAP1B	0.019	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.031	0.17	-9999	-0.45	44	44
fibrinolysis	-0.028	0.15	-9999	-0.41	44	44
HCK	-0.028	0.16	-9999	-0.54	31	31
dendritic cell antigen processing and presentation	-0.12	0.24	-9999	-0.42	94	94
VTN	-0.058	0.19	-9999	-0.5	54	54
alphaM/beta2 Integrin/CYR61	-0.031	0.16	-9999	-0.44	46	46
LPA	0	0	-9999	-10000	0	0
LRP1	0.015	0.033	-9999	-0.24	6	6
cell migration	-0.089	0.22	-9999	-0.43	89	89
FN1	0	0.1	-9999	-0.51	13	13
alphaM/beta2 Integrin/Thy1	-0.029	0.16	-9999	-0.44	46	46
MPO	-0.033	0.16	-9999	-0.53	34	34
KNG1	-0.003	0.047	-9999	-0.24	13	13
RAP1/GDP	0.026	0	-9999	-10000	0	0
ROCK1	-0.11	0.22	-9999	-0.38	107	107
ELA2	0	0	-9999	-10000	0	0
PLG	0	0	-9999	-10000	0	0
CTGF	0.007	0.058	-9999	-0.26	15	15
alphaM/beta2 Integrin/Hck	-0.052	0.23	-9999	-0.62	46	46
ITGAM	-0.006	0.099	-9999	-0.55	11	11
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.14	0.29	-9999	-0.45	139	139
HP	-0.12	0.23	-9999	-0.5	93	93
leukocyte adhesion	-0.034	0.19	-9999	-0.52	37	37
SELP	-0.17	0.26	-9999	-0.54	123	123

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	-0.037	0.12	-10000	0	-0.23	101	101
epithelial cell differentiation	-0.042	0.14	-10000	0	-0.26	101	101
CYFIP2	-0.01	0.12	-10000	0	-0.54	19	19
ENAH	0.005	0.095	-10000	0	-0.31	2	2
EGFR	-0.007	0.086	-10000	0	-0.27	32	32
EPHA2	0.013	0.058	-10000	0	-0.54	4	4
MYO6	-0.039	0.13	-10000	0	-0.24	101	101
CTNNB1	0.019	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.02	0.079	-10000	0	-0.32	19	19
AQP5	-0.043	0.12	-10000	0	-0.32	15	15
CTNND1	0.019	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.037	0.12	-10000	0	-0.24	101	101
regulation of calcium-dependent cell-cell adhesion	-0.046	0.13	-10000	0	-0.24	110	110
EGF	-0.031	0.15	-10000	0	-0.42	41	41
NCKAP1	0.019	0	-10000	0	-10000	0	0
AQP3	-0.086	0.2	-10000	0	-0.52	49	49
cortical microtubule organization	-0.042	0.14	-10000	0	-0.26	101	101
GO:0000145	-0.038	0.12	-10000	0	-0.23	101	101
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.04	0.14	-10000	0	-0.26	101	101
MLLT4	0	0.067	-10000	0	-0.24	26	26
ARF6/GDP	-0.055	0.089	-10000	0	-0.43	2	2
ARF6	0.019	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.045	0.034	-10000	0	-0.28	4	4
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.024	0.12	-10000	0	-0.29	2	2
PVRL2	0.019	0	-10000	0	-10000	0	0
ZYX	-0.038	0.13	-10000	0	-0.24	101	101
ARF6/GTP	0.05	0.032	-10000	0	-0.25	4	4
CDH1	-0.13	0.25	-10000	0	-0.54	101	101
EGFR/EGFR/EGF/EGF	-0.092	0.13	-10000	0	-0.27	119	119
RhoA/GDP	-0.036	0.13	-10000	0	-0.24	101	101
actin cytoskeleton organization	-0.033	0.12	-10000	0	-0.23	101	101
IGF-1R heterotetramer	0.016	0.027	-10000	0	-0.24	4	4
GIT1	0.019	0	-10000	0	-10000	0	0
IGF1R	0.016	0.027	-10000	0	-0.24	4	4
IGF1	0.009	0.065	-10000	0	-0.37	9	9
DIAPH1	-0.026	0.14	-10000	0	-0.63	19	19
Wnt receptor signaling pathway	0.042	0.14	0.26	101	-10000	0	101
RHOA	0.019	0	-10000	0	-10000	0	0
RhoA/GTP	-0.055	0.09	-10000	0	-0.43	2	2
CTNNA1	0.019	0	-10000	0	-10000	0	0
VCL	-0.034	0.13	-10000	0	-0.24	101	101
EFNA1	0.019	0	-10000	0	-10000	0	0
LPP	-0.031	0.12	-10000	0	-0.23	1	1
Ephrin A1/EPHA2	-0.066	0.11	-10000	0	-0.23	103	103
SEC6/SEC8	-0.061	0.094	-10000	0	-0.3	7	7
MGAT3	-0.047	0.13	-10000	0	-0.25	110	110
HGF/MET	-0.088	0.14	-10000	0	-0.27	115	115
HGF	0	0.085	-10000	0	-0.34	19	19
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.038	0.12	-10000	0	-0.23	101	101
actin cable formation	0.021	0.097	-10000	0	-0.24	2	2
KIAA1543	-0.059	0.14	-10000	0	-0.25	115	115
KIFC3	-0.038	0.13	-10000	0	-0.24	101	101
NCK1	0.019	0	-10000	0	-10000	0	0
EXOC3	0.018	0.014	-10000	0	-0.24	1	1
ACTN1	-0.039	0.13	-10000	0	-0.24	102	102
NCK1/GIT1	0.028	0	-10000	0	-10000	0	0
mol:GDP	-0.042	0.14	-10000	0	-0.26	101	101
EXOC4	0.019	0	-10000	0	-10000	0	0
STX4	-0.038	0.13	-10000	0	-0.24	101	101
PIP5K1C	-0.038	0.13	-10000	0	-0.24	101	101
LIMA1	0.019	0	-10000	0	-10000	0	0
ABI1	0.019	0	-10000	0	-10000	0	0
ROCK1	-0.003	0.11	-10000	0	-0.37	2	2
adherens junction assembly	-0.039	0.14	-10000	0	-0.36	20	20
IGF-1R heterotetramer/IGF1	-0.068	0.11	-10000	0	-0.24	104	104
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.015	0.046	-10000	0	-10000	0	0
MET	-0.024	0.14	-10000	0	-0.43	35	35
PLEKHA7	-0.049	0.14	-10000	0	-0.25	112	112
mol:GTP	0.043	0.034	-10000	0	-0.28	4	4
establishment of epithelial cell apical/basal polarity	-0.015	0.12	-10000	0	-0.29	7	7
cortical actin cytoskeleton stabilization	-0.037	0.12	-10000	0	-0.23	101	101
regulation of cell-cell adhesion	-0.033	0.12	-10000	0	-0.23	101	101
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.038	0.12	-10000	0	-0.23	101	101

×

a4b1 and a4b7 Integrin signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.017	0.019	-9999	-0.24	2	2
ITGB7	-0.063	0.2	-9999	-0.54	54	54
ITGA4	-0.043	0.18	-9999	-0.54	41	41
alpha4/beta7 Integrin	-0.076	0.2	-9999	-0.42	84	84
alpha4/beta1 Integrin	-0.019	0.13	-9999	-0.38	41	41

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.07	0.11	0.32	21	-10000	0	21
SMARCC2	0.021	0	-10000	0	-10000	0	0
SMARCC1	0.021	0	-10000	0	-10000	0	0
TBX21	-0.28	0.41	-10000	0	-0.84	119	119
SUMO2	0.021	0.009	-10000	0	-10000	0	0
STAT1 (dimer)	-0.012	0.12	-10000	0	-0.33	39	39
FKBP4	0.018	0.014	-10000	0	-0.24	1	1
FKBP5	-0.021	0.14	-10000	0	-0.54	26	26
GR alpha/HSP90/FKBP51/HSP90	0.1	0.14	0.31	72	-0.26	8	80
PRL	-0.11	0.17	-10000	0	-0.54	20	20
cortisol/GR alpha (dimer)/TIF2	0.26	0.29	0.59	134	-10000	0	134
RELA	-0.006	0.066	-10000	0	-0.22	5	5
FGG	0.2	0.23	0.5	99	-0.47	1	100
GR beta/TIF2	0.14	0.14	0.33	94	-10000	0	94
IFNG	-0.52	0.6	-10000	0	-1.2	140	140
apoptosis	0.086	0.15	0.49	36	-10000	0	36
CREB1	0.019	0.016	-10000	0	-10000	0	0
histone acetylation	-0.078	0.17	-10000	0	-0.37	68	68
BGLAP	-0.091	0.17	-10000	0	-0.53	11	11
GR/PKAc	0.13	0.11	0.3	76	-10000	0	76
NF kappa B1 p50/RelA	-0.006	0.12	-10000	0	-0.3	21	21
SMARCD1	0.021	0	-10000	0	-10000	0	0
MDM2	0.1	0.11	0.25	114	-10000	0	114
GATA3	-0.1	0.23	-10000	0	-0.54	80	80
AKT1	0.01	0.001	-10000	0	-10000	0	0
CSF2	-0.1	0.18	-10000	0	-0.5	31	31
GSK3B	0.021	0.009	-10000	0	-10000	0	0
NR1I3	0.096	0.14	0.48	30	-10000	0	30
CSN2	0.16	0.18	0.42	83	-10000	0	83
BRG1/BAF155/BAF170/BAF60A	0.058	0.001	-10000	0	-10000	0	0
NFATC1	0.007	0.086	-10000	0	-0.54	9	9
POU2F1	0.013	0.027	-10000	0	-10000	0	0
CDKN1A	0.033	0.032	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.002	0.009	-10000	0	-10000	0	0
SFN	-0.034	0.1	-10000	0	-0.24	73	73
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.084	0.14	0.31	53	-0.3	9	62
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	0.083	0.15	0.46	31	-10000	0	31
JUN	-0.19	0.22	-10000	0	-0.46	111	111
IL4	-0.12	0.19	-10000	0	-0.52	39	39
CDK5R1	0.018	0.029	-10000	0	-0.54	1	1
PRKACA	0.019	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.095	0.17	0.22	19	-0.39	59	78
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.11	0.13	0.31	66	-0.26	3	69
cortisol/GR alpha (monomer)	0.31	0.36	0.72	134	-0.42	1	135
NCOA2	0.018	0.014	-10000	0	-0.24	1	1
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.035	0.073	-10000	0	-0.29	11	11
AP-1/NFAT1-c-4	-0.27	0.31	-10000	0	-0.64	116	116
AFP	-0.14	0.15	-10000	0	-0.51	5	5
SUV420H1	0.019	0	-10000	0	-10000	0	0
IRF1	0.061	0.34	0.46	57	-0.76	43	100
TP53	0.043	0.013	-10000	0	-10000	0	0
PPP5C	0.019	0	-10000	0	-10000	0	0
KRT17	-0.27	0.31	-10000	0	-0.7	87	87
KRT14	-0.18	0.19	-10000	0	-0.58	29	29
TBP	0.03	0.007	-10000	0	-10000	0	0
CREBBP	0.044	0.044	-10000	0	-10000	0	0
HDAC1	0.017	0.029	-10000	0	-0.54	1	1
HDAC2	0.017	0.005	-10000	0	-10000	0	0
AP-1	-0.27	0.32	-10000	0	-0.64	118	118
MAPK14	0.02	0.008	-10000	0	-10000	0	0
MAPK10	-0.03	0.1	-10000	0	-0.24	70	70
MAPK11	0.021	0.009	-10000	0	-10000	0	0
KRT5	-0.33	0.43	-10000	0	-0.94	92	92
interleukin-1 receptor activity	-0.002	0.005	-10000	0	-10000	0	0
NCOA1	0.023	0.002	-10000	0	-10000	0	0
STAT1	-0.012	0.12	-10000	0	-0.33	39	39
CGA	-0.11	0.17	-10000	0	-0.47	35	35
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.15	0.14	0.35	84	-10000	0	84
MAPK3	0.021	0.009	-10000	0	-10000	0	0
MAPK1	0.02	0.008	-10000	0	-10000	0	0
ICAM1	-0.15	0.26	-10000	0	-0.6	68	68
NFKB1	-0.006	0.066	-10000	0	-0.21	7	7
MAPK8	-0.17	0.21	-10000	0	-0.43	112	112
MAPK9	0.02	0.008	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.081	0.16	0.5	36	-10000	0	36
BAX	0.034	0.019	-10000	0	-10000	0	0
POMC	-0.27	0.52	-10000	0	-1.7	42	42
EP300	0.044	0.044	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/p53	0.28	0.29	0.61	134	-10000	0	134
proteasomal ubiquitin-dependent protein catabolic process	0.069	0.085	0.2	77	-10000	0	77
SGK1	0.1	0.064	-10000	0	-10000	0	0
IL13	-0.29	0.36	-10000	0	-0.82	92	92
IL6	-0.17	0.3	-10000	0	-0.61	83	83
PRKACG	0.002	0.02	-10000	0	-0.24	2	2
IL5	-0.26	0.31	-10000	0	-0.77	76	76
IL2	-0.25	0.29	-10000	0	-0.7	73	73
CDK5	0.02	0.004	-10000	0	-10000	0	0
PRKACB	0.018	0.014	-10000	0	-0.24	1	1
HSP90AA1	0.017	0.029	-10000	0	-0.54	1	1
IL8	-0.18	0.27	-10000	0	-0.64	67	67
CDK5R1/CDK5	0.029	0.024	-10000	0	-0.38	1	1
NF kappa B1 p50/RelA/PKAc	0.021	0.09	-10000	0	-0.28	5	5
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.26	0.27	0.56	133	-10000	0	133
SMARCA4	0.021	0	-10000	0	-10000	0	0
chromatin remodeling	0.19	0.17	0.41	103	-10000	0	103
NF kappa B1 p50/RelA/Cbp	0.046	0.11	0.32	1	-0.31	2	3
JUN (dimer)	-0.19	0.22	-10000	0	-0.46	111	111
YWHAH	0.019	0	-10000	0	-10000	0	0
VIPR1	-0.25	0.39	-10000	0	-0.78	119	119
NR3C1	0.19	0.23	0.48	114	-10000	0	114
NR4A1	-0.027	0.15	-10000	0	-0.42	43	43
TIF2/SUV420H1	0.028	0.009	-10000	0	-10000	0	0
MAPKKK cascade	0.086	0.15	0.49	36	-10000	0	36
cortisol/GR alpha (dimer)/Src-1	0.27	0.29	0.6	135	-0.35	1	136
PBX1	-0.005	0.079	-10000	0	-0.28	25	25
POU1F1	-0.002	0.028	-10000	0	-10000	0	0
SELE	-0.23	0.41	-10000	0	-0.97	71	71
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.19	0.17	0.41	103	-10000	0	103
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.26	0.27	0.56	133	-10000	0	133
mol:cortisol	0.18	0.23	0.43	132	-0.24	1	133
MMP1	-0.17	0.34	-10000	0	-1.3	27	27

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.014	0.04	-10000	0	-0.3	5	5
GNB1/GNG2	-0.057	0.085	-10000	0	-0.2	93	93
AKT1	-0.011	0.12	-10000	0	-0.2	93	93
EGF	-0.031	0.15	-10000	0	-0.42	41	41
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.013	0.097	-10000	0	-0.25	36	36
mol:Ca2+	-0.04	0.17	-10000	0	-0.31	94	94
LYN	0.027	0.08	-10000	0	-0.29	15	15
RhoA/GTP	-0.035	0.055	-10000	0	-0.13	93	93
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.064	0.21	-10000	0	-0.37	107	107
GNG2	0.01	0.071	-10000	0	-0.54	6	6
ARRB2	0.019	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0	0.11	-10000	0	-0.48	12	12
G beta5/gamma2	-0.073	0.11	-10000	0	-0.26	93	93
PRKCH	-0.047	0.18	-10000	0	-0.34	95	95
DNM1	-0.008	0.08	-10000	0	-0.24	38	38
TXA2/TP beta/beta Arrestin3	-0.006	0.024	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	0.002	0.095	-10000	0	-0.54	11	11
G12 family/GTP	-0.087	0.13	-10000	0	-0.31	94	94
ADRBK1	0.019	0	-10000	0	-10000	0	0
ADRBK2	0.014	0.05	-10000	0	-0.54	3	3
RhoA/GTP/ROCK1	0.025	0.001	-10000	0	-10000	0	0
mol:GDP	0.012	0.12	0.3	19	-10000	0	19
mol:NADP	0.014	0.042	-10000	0	-0.29	6	6
RAB11A	0.019	0	-10000	0	-10000	0	0
PRKG1	-0.087	0.13	-10000	0	-0.24	148	148
mol:IP3	-0.058	0.2	-10000	0	-0.39	94	94
cell morphogenesis	0.025	0.001	-10000	0	-10000	0	0
PLCB2	-0.091	0.27	-10000	0	-0.53	94	94
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.12	0.13	-10000	0	-0.24	117	117
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.016	0.095	-10000	0	-0.27	27	27
RHOA	0.019	0	-10000	0	-10000	0	0
PTGIR	0.014	0.05	-10000	0	-0.54	3	3
PRKCB1	-0.056	0.2	-10000	0	-0.37	94	94
GNAQ	0.019	0	-10000	0	-10000	0	0
mol:L-citrulline	0.014	0.042	-10000	0	-0.29	6	6
TXA2/TXA2-R family	-0.097	0.28	-10000	0	-0.55	94	94
LCK	-0.057	0.14	-10000	0	-0.23	129	129
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.024	0.05	-10000	0	-0.24	4	4
TXA2-R family/G12 family/GDP/G beta/gamma	0.034	0.029	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.033	0.051	-10000	0	-0.26	2	2
MAPK14	-0.03	0.14	-10000	0	-0.24	101	101
TGM2/GTP	-0.083	0.22	-10000	0	-0.44	94	94
MAPK11	-0.03	0.14	-10000	0	-0.24	101	101
ARHGEF1	-0.014	0.1	-10000	0	-0.18	93	93
GNAI2	0.019	0	-10000	0	-10000	0	0
JNK cascade	-0.061	0.21	-10000	0	-0.4	94	94
RAB11/GDP	0.019	0.002	-10000	0	-10000	0	0
ICAM1	-0.037	0.16	-10000	0	-0.29	93	93
cAMP biosynthetic process	-0.06	0.19	-10000	0	-0.37	94	94
Gq family/GTP/EBP50	-0.012	0.095	-10000	0	-0.2	72	72
actin cytoskeleton reorganization	0.025	0.001	-10000	0	-10000	0	0
SRC	0.037	0.05	-10000	0	-0.24	2	2
GNB5	0.017	0.029	-10000	0	-0.54	1	1
GNB1	0.019	0	-10000	0	-10000	0	0
EGF/EGFR	-0.11	0.15	-10000	0	-0.28	125	125
VCAM1	-0.06	0.2	-10000	0	-0.38	93	93
TP beta/Gq family/GDP/G beta5/gamma2	0	0.11	-10000	0	-0.48	12	12
platelet activation	-0.034	0.18	-10000	0	-0.32	94	94
PGI2/IP	0.011	0.037	-10000	0	-0.39	3	3
PRKACA	0.014	0.055	-10000	0	-0.26	14	14
Gq family/GDP/G beta5/gamma2	0	0.11	-10000	0	-0.46	12	12
TXA2/TP beta/beta Arrestin2	-0.01	0.03	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.018	0.056	-10000	0	-0.25	15	15
mol:DAG	-0.065	0.22	-10000	0	-0.42	94	94
EGFR	-0.007	0.086	-10000	0	-0.27	32	32
TXA2/TP alpha	-0.089	0.26	-10000	0	-0.51	94	94
Gq family/GTP	-0.045	0.097	-10000	0	-0.24	72	72
YES1	0.037	0.05	-10000	0	-0.24	2	2
GNAI2/GTP	-0.01	0.044	-10000	0	-0.24	5	5
PGD2/DP	0.002	0.069	-10000	0	-0.39	11	11
SLC9A3R1	0.019	0	-10000	0	-10000	0	0
FYN	0.037	0.05	-10000	0	-0.24	2	2
mol:NO	0.014	0.042	-10000	0	-0.29	6	6
GNA15	0.002	0.095	-10000	0	-0.54	11	11
PGK/cGMP	-0.038	0.078	-10000	0	-0.32	3	3
RhoA/GDP	0.019	0.002	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0.039	0.066	-10000	0	-0.37	2	2
NOS3	0.014	0.042	-10000	0	-0.29	6	6
RAC1	0.019	0	-10000	0	-10000	0	0
PRKCA	-0.047	0.18	-10000	0	-0.34	94	94
PRKCB	-0.088	0.23	-10000	0	-0.44	95	95
PRKCE	-0.04	0.18	-10000	0	-0.34	94	94
PRKCD	-0.054	0.2	-10000	0	-0.38	94	94
PRKCG	-0.057	0.2	-10000	0	-0.38	94	94
muscle contraction	-0.093	0.26	-10000	0	-0.52	94	94
PRKCZ	-0.048	0.19	-10000	0	-0.35	94	94
ARR3	0.003	0.015	-10000	0	-0.24	1	1
TXA2/TP beta	0.032	0.06	-10000	0	-0.23	14	14
PRKCQ	-0.091	0.23	-10000	0	-0.44	96	96
MAPKKK cascade	-0.089	0.25	-10000	0	-0.5	94	94
SELE	-0.056	0.19	-10000	0	-0.36	93	93
TP beta/GNAI2/GDP/G beta/gamma	0.041	0.064	-10000	0	-0.37	2	2
ROCK1	0.019	0	-10000	0	-10000	0	0
GNA14	-0.084	0.22	-10000	0	-0.53	69	69
chemotaxis	-0.12	0.32	-10000	0	-0.64	93	93
GNA12	0.019	0	-10000	0	-10000	0	0
GNA13	0.019	0	-10000	0	-10000	0	0
GNA11	0.019	0	-10000	0	-10000	0	0
Rac1/GTP	0.014	0.002	-10000	0	-10000	0	0

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.024	0.18	0.29	21	-0.42	32	53
PTK2B	0.008	0.076	-10000	0	-0.54	7	7
mol:Ca2+	-0.029	0.18	-10000	0	-0.46	17	17
EDN1	-0.016	0.13	0.24	21	-0.35	19	40
EDN3	-0.063	0.15	-10000	0	-0.3	86	86
EDN2	0	0	-10000	0	-10000	0	0
HRAS/GDP	-0.069	0.22	-10000	0	-0.46	60	60
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.038	0.18	-10000	0	-0.42	43	43
ADCY4	-0.036	0.16	-10000	0	-0.37	38	38
ADCY5	-0.095	0.19	-10000	0	-0.34	107	107
ADCY6	-0.034	0.15	-10000	0	-0.36	38	38
ADCY7	-0.035	0.15	-10000	0	-0.35	43	43
ADCY1	-0.077	0.18	-10000	0	-0.38	60	60
ADCY2	-0.087	0.16	-10000	0	-0.36	65	65
ADCY3	-0.033	0.15	-10000	0	-0.36	37	37
ADCY8	-0.049	0.16	-10000	0	-0.35	50	50
ADCY9	-0.033	0.15	-10000	0	-0.36	36	36
arachidonic acid secretion	-0.035	0.18	-10000	0	-0.39	47	47
ETB receptor/Endothelin-1/Gq/GTP	-0.039	0.14	-10000	0	-0.32	55	55
GNAO1	-0.094	0.13	-10000	0	-0.24	156	156
HRAS	0.019	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	-0.003	0.18	0.37	23	-0.38	32	55
ETA receptor/Endothelin-1/Gs/GTP	-0.023	0.18	0.35	19	-0.36	44	63
mol:GTP	0.001	0.004	-10000	0	-10000	0	0
COL3A1	-0.044	0.2	0.29	12	-0.4	51	63
EDNRB	-0.025	0.095	-10000	0	-0.25	51	51
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.063	0.25	-10000	0	-0.62	46	46
CYSLTR1	-0.071	0.27	-10000	0	-0.62	56	56
SLC9A1	-0.006	0.1	0.21	20	-0.27	15	35
mol:GDP	-0.084	0.23	-10000	0	-0.49	64	64
SLC9A3	-0.18	0.3	-10000	0	-0.59	103	103
RAF1	-0.066	0.21	-10000	0	-0.46	55	55
JUN	-0.033	0.18	-10000	0	-0.5	14	14
JAK2	-0.031	0.18	0.29	20	-0.42	36	56
mol:IP3	-0.053	0.2	-10000	0	-0.42	58	58
ETA receptor/Endothelin-1	-0.027	0.23	0.44	23	-0.49	32	55
PLCB1	-0.001	0.1	-10000	0	-0.54	13	13
PLCB2	0.001	0.099	-10000	0	-0.54	12	12
ETA receptor/Endothelin-3	-0.055	0.14	-10000	0	-0.3	59	59
FOS	-0.03	0.17	-10000	0	-0.46	21	21
Gai/GDP	-0.034	0.091	-10000	0	-0.62	2	2
CRK	0.019	0.001	-10000	0	-10000	0	0
mol:Ca ++	-0.068	0.23	-10000	0	-0.49	54	54
BCAR1	0.019	0.001	-10000	0	-10000	0	0
PRKCB1	-0.049	0.19	-10000	0	-0.4	58	58
GNAQ	0.02	0.005	-10000	0	-10000	0	0
GNAZ	-0.016	0.094	-10000	0	-0.26	46	46
GNAL	-0.02	0.1	-10000	0	-0.27	49	49
Gs family/GDP	-0.093	0.21	-10000	0	-0.46	63	63
ETA receptor/Endothelin-1/Gq/GTP	-0.04	0.17	0.23	15	-0.39	47	62
MAPK14	-0.027	0.15	-10000	0	-0.36	37	37
TRPC6	-0.031	0.18	-10000	0	-0.49	16	16
GNAI2	0.019	0	-10000	0	-10000	0	0
GNAI3	0.019	0	-10000	0	-10000	0	0
GNAI1	0.005	0.058	-10000	0	-0.24	19	19
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.036	0.16	-10000	0	-0.35	49	49
ETB receptor/Endothelin-2	-0.015	0.064	-10000	0	-0.24	5	5
ETB receptor/Endothelin-3	-0.058	0.12	-10000	0	-0.27	49	49
ETB receptor/Endothelin-1	-0.025	0.12	-10000	0	-0.33	19	19
MAPK3	-0.042	0.19	-10000	0	-0.46	38	38
MAPK1	-0.042	0.19	-10000	0	-0.47	36	36
Rac1/GDP	-0.069	0.22	-10000	0	-0.46	62	62
cAMP biosynthetic process	-0.089	0.18	-10000	0	-0.38	64	64
MAPK8	-0.037	0.19	-10000	0	-0.43	41	41
SRC	0.019	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.027	0.079	-10000	0	-0.26	11	11
p130Cas/CRK/Src/PYK2	-0.073	0.23	-10000	0	-0.47	63	63
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.069	0.22	-10000	0	-0.46	62	62
COL1A2	-0.055	0.2	-10000	0	-0.49	29	29
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.011	0.087	-10000	0	-0.23	18	18
mol:DAG	-0.052	0.2	-10000	0	-0.42	58	58
MAP2K2	-0.051	0.2	-10000	0	-0.44	48	48
MAP2K1	-0.051	0.2	-10000	0	-0.44	49	49
EDNRA	-0.021	0.13	0.24	21	-0.31	28	49
positive regulation of muscle contraction	-0.012	0.15	0.25	21	-0.36	30	51
Gq family/GDP	-0.12	0.22	-10000	0	-0.5	72	72
HRAS/GTP	-0.081	0.22	-10000	0	-0.45	71	71
PRKCH	-0.043	0.19	-10000	0	-0.41	52	52
RAC1	0.019	0	-10000	0	-10000	0	0
PRKCA	-0.044	0.19	-10000	0	-0.42	51	51
PRKCB	-0.12	0.26	-10000	0	-0.48	94	94
PRKCE	-0.04	0.19	-10000	0	-0.41	51	51
PRKCD	-0.041	0.19	-10000	0	-0.41	52	52
PRKCG	-0.045	0.19	-10000	0	-0.42	51	51
regulation of vascular smooth muscle contraction	-0.039	0.2	-10000	0	-0.56	19	19
PRKCQ	-0.13	0.25	-10000	0	-0.45	105	105
PLA2G4A	-0.04	0.2	-10000	0	-0.42	47	47
GNA14	-0.083	0.22	-10000	0	-0.53	69	69
GNA15	0.003	0.095	-10000	0	-0.54	11	11
GNA12	0.019	0	-10000	0	-10000	0	0
GNA11	0.02	0.004	-10000	0	-10000	0	0
Rac1/GTP	-0.004	0.18	0.38	23	-0.38	32	55
MMP1	-0.059	0.26	-10000	0	-0.89	27	27

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.017	0.029	-9999	-0.54	1	1
Caspase 8 (4 units)	-0.038	0.13	-9999	-0.44	11	11
NEF	-0.029	0.054	-9999	-0.19	19	19
NFKBIA	-0.017	0.054	-9999	-10000	0	0
BIRC3	-0.16	0.29	-9999	-0.56	128	128
CYCS	-0.049	0.14	-9999	-0.44	11	11
RIPK1	0.019	0	-9999	-10000	0	0
CD247	-0.23	0.33	-9999	-0.67	128	128
MAP2K7	-0.042	0.14	-9999	-0.37	17	17
protein ubiquitination	-0.012	0.12	-9999	-0.37	13	13
CRADD	0.018	0.014	-9999	-0.24	1	1
DAXX	0.019	0	-9999	-10000	0	0
FAS	0.007	0.081	-9999	-0.54	8	8
BID	-0.059	0.15	-9999	-0.25	121	121
NF-kappa-B/RelA/I kappa B alpha	-0.06	0.15	-9999	-0.27	128	128
TRADD	0.019	0	-9999	-10000	0	0
MAP3K5	0.016	0.041	-9999	-0.54	2	2
CFLAR	0.019	0	-9999	-10000	0	0
FADD	0.018	0.014	-9999	-0.24	1	1
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.06	0.15	-9999	-0.27	128	128
MAPK8	-0.033	0.13	-9999	-0.36	15	15
APAF1	0.019	0	-9999	-10000	0	0
TRAF1	-0.001	0.098	-9999	-0.46	15	15
TRAF2	0.019	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.069	0.15	-9999	-0.27	122	122
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	-0.034	0.15	-9999	-0.33	59	59
CHUK	-0.015	0.13	-9999	-0.4	13	13
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.046	0.056	-9999	-0.26	12	12
TCRz/NEF	-0.21	0.31	-9999	-0.57	147	147
TNF	-0.095	0.22	-9999	-0.54	75	75
FASLG	-0.28	0.4	-9999	-0.74	147	147
NFKB1	-0.017	0.054	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.035	0.14	-9999	-0.32	76	76
CASP6	-0.01	0.11	-9999	-0.7	2	2
CASP7	-0.15	0.3	-9999	-0.55	128	128
RELA	-0.017	0.054	-9999	-10000	0	0
CASP2	0.019	0	-9999	-10000	0	0
CASP3	-0.15	0.3	-9999	-0.55	128	128
TNFRSF1A	0.019	0	-9999	-10000	0	0
TNFR1A/BAG4	0.027	0.021	-9999	-0.38	1	1
CASP8	0.016	0.041	-9999	-0.54	2	2
CASP9	0.019	0	-9999	-10000	0	0
MAP3K14	-0.024	0.14	-9999	-0.3	58	58
APAF-1/Caspase 9	-0.16	0.2	-9999	-0.43	128	128
BCL2	-0.024	0.12	-9999	-0.36	10	10

×

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	-0.008	0.088	-10000	0	-0.28	31	31
CDKN2C	0.029	0.012	-10000	0	-10000	0	0
CDKN2A	-0.11	0.14	-10000	0	-0.25	171	171
CCND2	0.022	0.064	0.18	23	-0.13	13	36
RB1	-0.026	0.063	-10000	0	-0.18	23	23
CDK4	0.03	0.063	0.19	23	-10000	0	23
CDK6	0.028	0.066	0.2	23	-0.16	1	24
G1/S progression	0.026	0.063	0.18	23	-10000	0	23

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.091	0.22	-9999	-0.44	101	101
KLHL20	-0.003	0.089	-9999	-0.22	7	7
CYFIP2	-0.01	0.12	-9999	-0.54	19	19
Rac1/GDP	-0.022	0.14	-9999	-0.25	99	99
ENAH	-0.091	0.22	-9999	-0.44	101	101
AP1M1	0.019	0	-9999	-10000	0	0
RAP1B	0.019	0	-9999	-10000	0	0
RAP1A	0.019	0	-9999	-10000	0	0
CTNNB1	0.019	0	-9999	-10000	0	0
CDC42/GTP	-0.048	0.079	-9999	-0.24	7	7
ABI1/Sra1/Nap1	-0.032	0.046	-9999	-0.17	15	15
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.088	0.19	-9999	-0.32	134	134
RAPGEF1	-0.064	0.19	-9999	-0.38	101	101
CTNND1	0.019	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.099	0.23	-9999	-0.46	101	101
CRK	-0.078	0.21	-9999	-0.41	101	101
E-cadherin/gamma catenin/alpha catenin	-0.064	0.16	-9999	-0.32	101	101
alphaE/beta7 Integrin	-0.032	0.14	-9999	-0.38	54	54
IQGAP1	0.019	0	-9999	-10000	0	0
NCKAP1	0.019	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.027	0.036	-9999	-10000	0	0
DLG1	-0.09	0.22	-9999	-0.44	101	101
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.035	0.057	-9999	-0.17	8	8
MLLT4	0	0.067	-9999	-0.24	26	26
ARF6/GTP/NME1/Tiam1	0.017	0.077	-9999	-0.29	22	22
PI3K	-0.044	0.072	-9999	-0.22	8	8
ARF6	0.019	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.09	0.19	-9999	-0.39	101	101
TIAM1	-0.015	0.13	-9999	-0.54	22	22
E-cadherin(dimer)/Ca2+	-0.04	0.14	-9999	-0.26	101	101
AKT1	-0.025	0.042	-9999	-10000	0	0
PIK3R1	0.019	0	-9999	-10000	0	0
CDH1	-0.13	0.25	-9999	-0.54	101	101
RhoA/GDP	-0.022	0.14	-9999	-0.25	99	99
actin cytoskeleton organization	0	0.068	-9999	-0.16	7	7
CDC42/GDP	-0.022	0.14	-9999	-0.25	99	99
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.048	0.12	-9999	-0.25	101	101
ITGB7	-0.063	0.2	-9999	-0.54	54	54
RAC1	0.019	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.042	0.15	-9999	-0.28	101	101
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.05	0.14	-9999	-0.27	101	101
mol:GDP	-0.038	0.16	-9999	-0.29	101	101
CDC42/GTP/IQGAP1	0.026	0	-9999	-10000	0	0
JUP	0.011	0.045	-9999	-0.24	11	11
p120 catenin/RhoA/GDP	-0.022	0.14	-9999	-0.3	10	10
RAC1/GTP/IQGAP1	0.026	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0.028	0	-9999	-10000	0	0
RHOA	0.019	0	-9999	-10000	0	0
CDC42	0.019	0	-9999	-10000	0	0
CTNNA1	0.019	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.003	0.051	-9999	-0.14	4	4
NME1	0.019	0	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	-0.09	0.22	-9999	-0.44	101	101
regulation of cell-cell adhesion	-0.043	0.071	-9999	-0.21	7	7
WASF2	-0.016	0.025	-9999	-0.11	2	2
Rap1/GTP	-0.016	0.12	-9999	-0.27	7	7
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.078	0.18	-9999	-0.3	134	134
CCND1	0.003	0.06	-9999	-0.16	4	4
VAV2	-0.073	0.22	-9999	-0.55	12	12
RAP1/GDP	-0.019	0.12	-9999	-0.27	9	9
adherens junction assembly	-0.086	0.21	-9999	-0.43	101	101
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.019	0	-9999	-10000	0	0
PIP5K1C	0.019	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.069	0.18	-9999	-0.28	134	134
E-cadherin/beta catenin	-0.086	0.17	-9999	-0.36	101	101
mol:GTP	0	0	-9999	-10000	0	0
SRC	-0.09	0.22	-9999	-0.44	101	101
PIK3CA	0.018	0.014	-9999	-0.24	1	1
Rac1/GTP	-0.066	0.095	-9999	-0.35	8	8
E-cadherin/beta catenin/alpha catenin	-0.059	0.16	-9999	-0.32	101	101
ITGAE	0.019	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.1	0.23	-9999	-0.47	101	101

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.003	0.11	-9999	-0.56	12	12
Syndecan-4/Syndesmos	-0.055	0.21	-9999	-0.49	65	65
positive regulation of JNK cascade	-0.07	0.22	-9999	-0.5	68	68
Syndecan-4/ADAM12	-0.063	0.21	-9999	-0.49	65	65
CCL5	-0.15	0.26	-9999	-0.54	110	110
Rac1/GDP	0.014	0	-9999	-10000	0	0
DNM2	0.019	0	-9999	-10000	0	0
ITGA5	0.015	0.03	-9999	-0.24	5	5
SDCBP	0.019	0	-9999	-10000	0	0
PLG	0	0.006	-9999	-10000	0	0
ADAM12	-0.001	0.069	-9999	-0.24	27	27
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.019	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.005	0.01	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.14	0.2	-9999	-0.56	66	66
Syndecan-4/CXCL12/CXCR4	-0.074	0.24	-9999	-0.53	68	68
Syndecan-4/Laminin alpha3	-0.064	0.21	-9999	-0.5	66	66
MDK	0.004	0.07	-9999	-0.3	17	17
Syndecan-4/FZD7	-0.056	0.21	-9999	-0.49	65	65
Syndecan-4/Midkine	-0.061	0.21	-9999	-0.49	65	65
FZD7	0.015	0.037	-9999	-0.32	4	4
Syndecan-4/FGFR1/FGF	-0.063	0.2	-9999	-0.46	65	65
THBS1	-0.005	0.075	-9999	-0.24	33	33
integrin-mediated signaling pathway	-0.061	0.21	-9999	-0.49	67	67
positive regulation of MAPKKK cascade	-0.07	0.22	-9999	-0.5	68	68
Syndecan-4/TACI	-0.19	0.25	-9999	-0.61	72	72
CXCR4	-0.024	0.15	-9999	-0.54	28	28
cell adhesion	0.019	0.059	-9999	-0.27	13	13
Syndecan-4/Dynamin	-0.055	0.21	-9999	-0.49	65	65
Syndecan-4/TSP1	-0.065	0.21	-9999	-0.49	65	65
Syndecan-4/GIPC	-0.055	0.21	-9999	-0.49	65	65
Syndecan-4/RANTES	-0.13	0.26	-9999	-0.63	67	67
ITGB1	0.017	0.019	-9999	-0.24	2	2
LAMA1	-0.2	0.1	-9999	-0.24	302	302
LAMA3	0	0.1	-9999	-0.51	13	13
RAC1	0.019	0	-9999	-10000	0	0
PRKCA	0.018	0.053	-9999	-0.27	6	6
Syndecan-4/alpha-Actinin	-0.056	0.21	-9999	-0.49	65	65
TFPI	0.014	0.04	-9999	-0.3	5	5
F2	-0.009	0.05	-9999	-0.24	15	15
alpha5/beta1 Integrin	0.025	0.029	-9999	-0.3	2	2
positive regulation of cell adhesion	-0.14	0.2	-9999	-0.53	72	72
ACTN1	0.017	0.029	-9999	-0.54	1	1
TNC	-0.002	0.1	-9999	-0.48	15	15
Syndecan-4/CXCL12	-0.066	0.22	-9999	-0.5	66	66
FGF6	0	0	-9999	-10000	0	0
RHOA	0.019	0	-9999	-10000	0	0
CXCL12	-0.005	0.11	-9999	-0.54	16	16
TNFRSF13B	-0.26	0.28	-9999	-0.54	179	179
FGF2	-0.004	0.08	-9999	-0.26	30	30
FGFR1	-0.003	0.072	-9999	-0.24	30	30
Syndecan-4/PI-4-5-P2	-0.066	0.2	-9999	-0.49	65	65
mol:GDP	0	0	-9999	-10000	0	0
FN1	0.001	0.096	-9999	-0.5	13	13
cell migration	0.002	0.006	-9999	-10000	0	0
PRKCD	0.02	0.005	-9999	-10000	0	0
vasculogenesis	-0.062	0.2	-9999	-0.47	65	65
SDC4	-0.069	0.22	-9999	-0.52	65	65
Syndecan-4/Tenascin C	-0.064	0.22	-9999	-0.51	67	67
Syndecan-4/PI-4-5-P2/PKC alpha	-0.004	0.008	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.055	0.21	-9999	-0.49	65	65
MMP9	-0.081	0.21	-9999	-0.52	68	68
Rac1/GTP	0.019	0.06	-9999	-0.28	13	13
cytoskeleton organization	-0.052	0.2	-9999	-0.47	65	65
GIPC1	0.019	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.057	0.21	-9999	-0.49	65	65

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.085	0.36	-10000	0	-0.84	63	63
NCK1/PAK1/Dok-R	-0.087	0.16	-10000	0	-0.42	63	63
NCK1/Dok-R	-0.16	0.44	-10000	0	-1.1	63	63
PIK3CA	0.018	0.014	-10000	0	-0.24	1	1
mol:beta2-estradiol	0.03	0.089	0.22	62	-10000	0	62
RELA	0.019	0	-10000	0	-10000	0	0
SHC1	0.019	0.002	-10000	0	-10000	0	0
Rac/GDP	0.014	0	-10000	0	-10000	0	0
F2	0.023	0.11	0.24	43	-0.26	14	57
TNIP2	0.019	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.12	0.4	-10000	0	-0.99	63	63
FN1	0	0.1	-10000	0	-0.51	13	13
PLD2	-0.15	0.44	-10000	0	-1.1	63	63
PTPN11	0.019	0	-10000	0	-10000	0	0
GRB14	-0.026	0.095	-10000	0	-0.24	59	59
ELK1	-0.12	0.4	-10000	0	-0.97	63	63
GRB7	-0.003	0.067	-10000	0	-0.24	26	26
PAK1	0.018	0.014	-10000	0	-0.24	1	1
Tie2/Ang1/alpha5/beta1 Integrin	-0.14	0.42	-10000	0	-1	63	63
CDKN1A	-0.021	0.23	-10000	0	-0.5	61	61
ITGA5	0.015	0.03	-10000	0	-0.24	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.16	0.44	-10000	0	-1.1	63	63
CRK	0.019	0	-10000	0	-10000	0	0
mol:NO	-0.047	0.28	-10000	0	-0.63	63	63
PLG	-0.16	0.44	-10000	0	-1.1	63	63
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.082	0.35	-10000	0	-0.83	63	63
GRB2	0.019	0	-10000	0	-10000	0	0
PIK3R1	0.019	0.002	-10000	0	-10000	0	0
ANGPT2	-0.036	0.18	-10000	0	-0.43	1	1
BMX	-0.2	0.45	-10000	0	-1.1	63	63
ANGPT1	-0.23	0.52	-10000	0	-1.3	62	62
tube development	-0.035	0.25	-10000	0	-0.55	63	63
ANGPT4	0.001	0.002	-10000	0	-10000	0	0
response to hypoxia	-0.01	0.028	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.18	0.45	-10000	0	-1.1	63	63
alpha5/beta1 Integrin	0.025	0.029	-10000	0	-0.3	2	2
FGF2	-0.005	0.08	-10000	0	-0.26	30	30
STAT5A (dimer)	-0.036	0.28	-10000	0	-0.62	61	61
mol:L-citrulline	-0.047	0.28	-10000	0	-0.63	63	63
AGTR1	0.001	0.003	-10000	0	-10000	0	0
MAPK14	-0.13	0.41	-10000	0	-1	63	63
Tie2/SHP2	-0.004	0.14	-10000	0	-1.2	2	2
TEK	-0.012	0.16	-10000	0	-1.4	2	2
RPS6KB1	-0.079	0.34	-10000	0	-0.81	63	63
Angiotensin II/AT1	0.004	0.005	-10000	0	-10000	0	0
Tie2/Ang1/GRB2	-0.16	0.45	-10000	0	-1.1	63	63
MAPK3	-0.13	0.41	-10000	0	-1	63	63
MAPK1	-0.13	0.41	-10000	0	-1	63	63
Tie2/Ang1/GRB7	-0.17	0.45	-10000	0	-1.1	63	63
NFKB1	0.019	0	-10000	0	-10000	0	0
MAPK8	-0.15	0.44	-10000	0	-1.1	63	63
PI3K	-0.11	0.4	-10000	0	-0.96	63	63
FES	-0.13	0.42	-10000	0	-1	63	63
Crk/Dok-R	-0.16	0.44	-10000	0	-1.1	63	63
Tie2/Ang1/ABIN2	-0.16	0.45	-10000	0	-1.1	63	63
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.07	0.32	-10000	0	-0.75	63	63
STAT5A	0.018	0.029	-10000	0	-0.54	1	1
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.079	0.34	-10000	0	-0.81	63	63
Tie2/Ang2	-0.064	0.31	-10000	0	-0.71	61	61
Tie2/Ang1	-0.17	0.47	-10000	0	-1.2	63	63
FOXO1	-0.068	0.32	-10000	0	-0.76	63	63
ELF1	0.027	0.011	-10000	0	-10000	0	0
ELF2	-0.15	0.43	-10000	0	-1.1	63	63
mol:Choline	-0.14	0.42	-10000	0	-1	63	63
cell migration	-0.049	0.088	-10000	0	-0.23	64	64
FYN	-0.045	0.28	-10000	0	-0.62	61	61
DOK2	-0.037	0.17	-10000	0	-0.54	37	37
negative regulation of cell cycle	-0.015	0.22	-10000	0	-0.46	61	61
ETS1	-0.012	0.087	-10000	0	-0.22	40	40
PXN	-0.052	0.29	-10000	0	-0.67	63	63
ITGB1	0.017	0.019	-10000	0	-0.24	2	2
NOS3	-0.061	0.31	-10000	0	-0.71	63	63
RAC1	0.019	0	-10000	0	-10000	0	0
TNF	-0.13	0.25	-10000	0	-0.46	115	115
MAPKKK cascade	-0.14	0.42	-10000	0	-1	63	63
RASA1	0.017	0.029	-10000	0	-0.54	1	1
Tie2/Ang1/Shc	-0.16	0.45	-10000	0	-1.1	63	63
NCK1	0.019	0	-10000	0	-10000	0	0
vasculogenesis	-0.037	0.25	-10000	0	-0.56	63	63
mol:Phosphatidic acid	-0.14	0.42	-10000	0	-1	63	63
mol:Angiotensin II	0.001	0.003	-10000	0	-10000	0	0
mol:NADP	-0.047	0.28	-10000	0	-0.63	63	63
Rac1/GTP	-0.14	0.28	-10000	0	-0.76	63	63
MMP2	-0.17	0.44	-10000	0	-1.1	63	63

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.15	0.32	-10000	0	-0.72	71	71
UGCG	-0.011	0.082	-10000	0	-0.78	2	2
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.061	0.21	-10000	0	-0.38	97	97
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.011	0.081	-10000	0	-0.76	2	2
mol:DAG	-0.011	0.079	-10000	0	-1.1	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.16	0.22	-10000	0	-0.47	112	112
FRAP1	-0.12	0.31	-10000	0	-0.55	112	112
FOXO3	-0.12	0.3	-10000	0	-0.55	112	112
AKT1	-0.14	0.33	-10000	0	-0.6	112	112
GAB2	0.016	0.031	-10000	0	-0.24	5	5
SMPD1	-0.007	0.058	-10000	0	-10000	0	0
SGMS1	-0.012	0.096	-10000	0	-1	2	2
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	0.023	0.008	-10000	0	-10000	0	0
CALM1	0.019	0	-10000	0	-10000	0	0
cell proliferation	-0.032	0.14	-10000	0	-0.25	58	58
EIF3A	0.019	0	-10000	0	-10000	0	0
PI3K	0.034	0.01	-10000	0	-10000	0	0
RPS6KB1	0.005	0.063	-10000	0	-10000	0	0
mol:sphingomyelin	-0.011	0.079	-10000	0	-1.1	2	2
natural killer cell activation	0.001	0.001	-10000	0	-10000	0	0
JAK3	-0.016	0.14	-10000	0	-0.54	25	25
PIK3R1	0.022	0.002	-10000	0	-10000	0	0
JAK1	0.022	0.002	-10000	0	-10000	0	0
NFKB1	0.019	0	-10000	0	-10000	0	0
MYC	-0.099	0.27	-10000	0	-0.52	95	95
MYB	-0.031	0.29	-10000	0	-1.3	19	19
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.17	0.36	-10000	0	-0.66	121	121
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.024	0.061	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.17	0.35	-10000	0	-0.64	121	121
Rac1/GDP	0.034	0.007	-10000	0	-10000	0	0
T cell proliferation	-0.15	0.33	-10000	0	-0.59	119	119
SHC1	0.02	0.001	-10000	0	-10000	0	0
RAC1	0.019	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.003	0.016	-10000	0	-0.066	19	19
PRKCZ	-0.16	0.34	-10000	0	-0.62	119	119
NF kappa B1 p50/RelA	-0.086	0.27	-10000	0	-0.47	112	112
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.17	0.35	-10000	0	-0.65	112	112
HSP90AA1	0.017	0.029	-10000	0	-0.54	1	1
RELA	0.019	0	-10000	0	-10000	0	0
IL2RA	-0.12	0.24	-10000	0	-0.54	93	93
IL2RB	-0.08	0.22	-10000	0	-0.54	67	67
TERT	0.001	0.072	-10000	0	-0.27	22	22
E2F1	0.007	0.11	-10000	0	-0.45	19	19
SOS1	0.02	0.001	-10000	0	-10000	0	0
RPS6	0.019	0	-10000	0	-10000	0	0
mol:cAMP	-0.002	0.008	0.031	19	-10000	0	19
PTPN11	0.02	0.001	-10000	0	-10000	0	0
IL2RG	-0.15	0.26	-10000	0	-0.54	112	112
actin cytoskeleton organization	-0.15	0.33	-10000	0	-0.59	119	119
GRB2	0.02	0.001	-10000	0	-10000	0	0
IL2	0.008	0.016	-10000	0	-0.24	1	1
PIK3CA	0.021	0.014	-10000	0	-0.24	1	1
Rac1/GTP	0.046	0.013	-10000	0	-10000	0	0
LCK	-0.19	0.27	-10000	0	-0.54	141	141
BCL2	-0.075	0.24	-10000	0	-0.44	95	95

×

IL2 signaling events mediated by STAT5

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
GAB2	0.016	0.03	-9999	-0.24	5	5
ELF1	-0.063	0.16	-9999	-0.34	93	93
CCNA2	0.017	0.029	-9999	-0.54	1	1
PIK3CA	0.019	0.014	-9999	-0.24	1	1
JAK3	-0.018	0.14	-9999	-0.54	25	25
PIK3R1	0.019	0	-9999	-10000	0	0
JAK1	0.02	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.18	0.37	-9999	-0.68	121	121
SHC1	0.02	0	-9999	-10000	0	0
SP1	0.004	0.093	-9999	-0.34	25	25
IL2RA	-0.17	0.36	-9999	-0.78	93	93
IL2RB	-0.082	0.22	-9999	-0.54	67	67
SOS1	0.019	0	-9999	-10000	0	0
IL2RG	-0.15	0.26	-9999	-0.54	112	112
G1/S transition of mitotic cell cycle	-0.03	0.23	-9999	-0.81	29	29
PTPN11	0.02	0	-9999	-10000	0	0
CCND2	-0.02	0.21	-9999	-0.78	25	25
LCK	-0.19	0.27	-9999	-0.54	141	141
GRB2	0.019	0	-9999	-10000	0	0
IL2	0.006	0.016	-9999	-0.24	1	1
CDK6	0.014	0.052	-9999	-0.46	4	4
CCND3	-0.14	0.31	-9999	-0.61	96	96

×

Paxillin-independent events mediated by a4b1 and a4b7

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.053	0.17	-9999	-0.35	84	84
CRKL	0.018	0.014	-9999	-0.24	1	1
Rac1/GDP	0.014	0	-9999	-10000	0	0
DOCK1	0.019	0	-9999	-10000	0	0
ITGA4	-0.043	0.18	-9999	-0.54	41	41
alpha4/beta7 Integrin/MAdCAM1	-0.21	0.22	-9999	-0.36	236	236
EPO	0.011	0.021	-9999	-0.24	2	2
alpha4/beta7 Integrin	-0.076	0.2	-9999	-0.42	84	84
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.019	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.019	0.13	-9999	-0.38	41	41
EPO/EPOR (dimer)	0.022	0.017	-9999	-10000	0	0
lamellipodium assembly	0.041	0.01	-9999	-10000	0	0
PIK3CA	0.018	0.014	-9999	-0.24	1	1
PI3K	0.028	0.009	-9999	-10000	0	0
ARF6	0.019	0	-9999	-10000	0	0
JAK2	-0.002	0.12	-9999	-0.31	41	41
PXN	0.019	0	-9999	-10000	0	0
PIK3R1	0.019	0	-9999	-10000	0	0
MADCAM1	-0.29	0.27	-9999	-0.54	203	203
cell adhesion	-0.21	0.22	-9999	-0.35	236	236
CRKL/CBL	0.028	0.009	-9999	-10000	0	0
ITGB1	0.017	0.019	-9999	-0.24	2	2
SRC	-0.051	0.18	-9999	-0.38	76	76
ITGB7	-0.063	0.2	-9999	-0.54	54	54
RAC1	0.019	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.059	0.2	-9999	-0.43	76	76
p130Cas/Crk/Dock1	-0.018	0.16	-9999	-0.47	28	28
VCAM1	-0.077	0.21	-9999	-0.54	63	63
RHOA	0.019	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.011	0.1	-9999	-0.28	41	41
BCAR1	-0.041	0.17	-9999	-0.35	76	76
EPOR	0.018	0.014	-9999	-0.24	1	1
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.019	0	-9999	-10000	0	0
GIT1	0.019	0	-9999	-10000	0	0
Rac1/GTP	0.041	0.01	-9999	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	0.026	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.019	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.008	0.076	-9999	-0.54	7	7
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.019	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.021	0.024	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
YES1	0.019	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	0.019	0	-9999	-10000	0	0
FYN	0.019	0	-9999	-10000	0	0
MAP3K12	0.019	0	-9999	-10000	0	0
FGR	-0.036	0.16	-9999	-0.54	36	36
p38 alpha/TAB1	-0.13	0.15	-9999	-0.29	126	126
PRKG1	-0.087	0.13	-9999	-0.24	148	148
DUSP8	-0.026	0.099	-9999	-0.24	63	63
PGK/cGMP/p38 alpha	-0.16	0.16	-9999	-0.32	145	145
apoptosis	-0.12	0.14	-9999	-0.28	123	123
RAL/GTP	0.026	0	-9999	-10000	0	0
LYN	-0.004	0.11	-9999	-0.54	15	15
DUSP1	0.015	0.033	-9999	-0.24	6	6
PAK1	0.018	0.014	-9999	-0.24	1	1
SRC	0.019	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.049	0	-9999	-10000	0	0
TRAF6	0.019	0	-9999	-10000	0	0
RAC1	0.019	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	0.019	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0.026	0	-9999	-10000	0	0
MAPK11	-0.16	0.21	-9999	-0.39	125	125
BLK	-0.34	0.26	-9999	-0.54	235	235
HCK	-0.028	0.16	-9999	-0.54	31	31
MAP2K3	0.019	0	-9999	-10000	0	0
DUSP16	0.019	0	-9999	-10000	0	0
DUSP10	0.013	0.058	-9999	-0.54	4	4
TRAF6/MEKK3	0.024	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	-0.12	0.18	-9999	-0.32	122	122
positive regulation of innate immune response	-0.17	0.23	-9999	-0.42	128	128
LCK	-0.2	0.27	-9999	-0.54	141	141
p38alpha-beta/MKP7	-0.15	0.22	-9999	-0.4	122	122
p38alpha-beta/MKP5	-0.16	0.22	-9999	-0.4	125	125
PGK/cGMP	-0.057	0.086	-9999	-0.16	148	148
PAK2	0.019	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.16	0.22	-9999	-0.4	122	122
CDC42	0.019	0	-9999	-10000	0	0
RALB	0.019	0	-9999	-10000	0	0
RALA	0.019	0	-9999	-10000	0	0
PAK3	-0.013	0.08	-9999	-0.24	39	39

×

LPA receptor mediated 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
GNB1/GNG2	-0.033	0.14	-9999	-0.31	66	66
NF kappa B1 p50/RelA/I kappa B alpha	-0.001	0.092	-9999	-0.31	10	10
AP1	-0.082	0.11	-9999	-0.28	70	70
mol:PIP3	-0.067	0.096	-9999	-0.32	23	23
AKT1	0.012	0.1	-9999	-0.32	11	11
PTK2B	-0.035	0.12	-9999	-0.26	66	66
RHOA	0.01	0.045	-9999	-0.29	1	1
PIK3CB	0.019	0.001	-9999	-10000	0	0
mol:Ca2+	-0.008	0.077	-9999	-0.33	7	7
MAGI3	0.019	0	-9999	-10000	0	0
RELA	0.019	0	-9999	-10000	0	0
apoptosis	-0.061	0.13	-9999	-0.29	73	73
HRAS/GDP	0.014	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	-0.07	0.12	-9999	-0.3	59	59
NF kappa B1 p50/RelA	-0.062	0.11	-9999	-0.31	44	44
endothelial cell migration	-0.065	0.16	-9999	-0.3	106	106
ADCY4	-0.086	0.18	-9999	-0.45	65	65
ADCY5	-0.13	0.22	-9999	-0.49	84	84
ADCY6	-0.084	0.18	-9999	-0.45	63	63
ADCY7	-0.085	0.18	-9999	-0.45	63	63
ADCY1	-0.12	0.2	-9999	-0.46	79	79
ADCY2	-0.11	0.18	-9999	-0.47	66	66
ADCY3	-0.084	0.18	-9999	-0.45	63	63
ADCY8	-0.093	0.18	-9999	-0.45	64	64
ADCY9	-0.084	0.18	-9999	-0.45	63	63
GSK3B	-0.026	0.12	-9999	-0.27	48	48
arachidonic acid secretion	-0.077	0.17	-9999	-0.42	63	63
GNG2	0.01	0.07	-9999	-0.54	6	6
TRIP6	0.025	0.022	-9999	-10000	0	0
GNAO1	-0.11	0.16	-9999	-0.38	77	77
HRAS	0.019	0	-9999	-10000	0	0
NFKBIA	-0.018	0.099	-9999	-0.32	16	16
GAB1	0.019	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.023	0.23	-9999	-0.94	22	22
JUN	-0.007	0.078	-9999	-0.24	36	36
LPA/LPA2/NHERF2	0.018	0.037	-9999	-0.32	3	3
TIAM1	-0.06	0.27	-9999	-1.1	22	22
PIK3R1	0.019	0.001	-9999	-10000	0	0
mol:IP3	-0.008	0.078	-9999	-0.34	7	7
PLCB3	0.023	0.033	-9999	-0.28	3	3
FOS	0.011	0.045	-9999	-0.24	11	11
positive regulation of mitosis	-0.077	0.17	-9999	-0.42	63	63
LPA/LPA1-2-3	-0.063	0.14	-9999	-0.3	75	75
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.019	0	-9999	-10000	0	0
stress fiber formation	-0.035	0.12	-9999	-0.29	48	48
GNAZ	-0.066	0.15	-9999	-0.34	70	70
EGFR/PI3K-beta/Gab1	-0.07	0.1	-9999	-0.33	23	23
positive regulation of dendritic cell cytokine production	-0.063	0.14	-9999	-0.3	75	75
LPA/LPA2/MAGI-3	0.019	0.037	-9999	-0.32	3	3
ARHGEF1	-0.024	0.12	-9999	-0.26	64	64
GNAI2	-0.047	0.14	-9999	-0.32	65	65
GNAI3	-0.047	0.14	-9999	-0.32	65	65
GNAI1	-0.054	0.14	-9999	-0.33	68	68
LPA/LPA3	-0.033	0.075	-9999	-0.16	85	85
LPA/LPA2	0.006	0.042	-9999	-0.39	3	3
LPA/LPA1	-0.067	0.16	-9999	-0.39	65	65
HB-EGF/EGFR	-0.046	0.14	-9999	-0.32	68	68
HBEGF	-0.049	0.16	-9999	-0.38	65	65
mol:DAG	-0.008	0.078	-9999	-0.34	7	7
cAMP biosynthetic process	-0.11	0.18	-9999	-0.46	67	67
NFKB1	0.019	0	-9999	-10000	0	0
SRC	0.019	0	-9999	-10000	0	0
GNB1	0.019	0.001	-9999	-10000	0	0
LYN	-0.036	0.15	-9999	-0.44	28	28
GNAQ	-0.007	0.056	-9999	-0.25	4	4
LPAR2	0.014	0.05	-9999	-0.54	3	3
LPAR3	-0.044	0.11	-9999	-0.24	85	85
LPAR1	-0.085	0.21	-9999	-0.53	64	64
IL8	-0.094	0.17	-9999	-0.38	57	57
PTK2	-0.055	0.13	-9999	-0.29	67	67
Rac1/GDP	0.014	0	-9999	-10000	0	0
CASP3	-0.061	0.13	-9999	-0.29	73	73
EGFR	-0.007	0.086	-9999	-0.27	32	32
PLCG1	-0.025	0.087	-9999	-0.25	27	27
PLD2	-0.055	0.13	-9999	-0.29	66	66
G12/G13	-0.028	0.13	-9999	-0.29	65	65
PI3K-beta	-0.041	0.086	-9999	-0.37	11	11
cell migration	-0.006	0.091	-9999	-0.27	23	23
SLC9A3R2	0.018	0.014	-9999	-0.24	1	1
PXN	-0.036	0.12	-9999	-0.29	48	48
HRAS/GTP	-0.079	0.17	-9999	-0.43	63	63
RAC1	0.019	0	-9999	-10000	0	0
MMP9	-0.082	0.21	-9999	-0.52	68	68
PRKCE	0.019	0	-9999	-10000	0	0
PRKCD	-0.001	0.075	-9999	-0.34	6	6
Gi(beta/gamma)	-0.076	0.17	-9999	-0.42	63	63
mol:LPA	-0.008	0.035	-9999	-0.18	2	2
TRIP6/p130 Cas/FAK1/Paxillin	-0.029	0.14	-9999	-0.35	27	27
MAPKKK cascade	-0.077	0.17	-9999	-0.42	63	63
contractile ring contraction involved in cytokinesis	0.01	0.045	-9999	-0.29	1	1
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.064	0.14	-9999	-0.32	69	69
GNA15	-0.016	0.083	-9999	-0.35	13	13
GNA12	0.019	0	-9999	-10000	0	0
GNA13	0.019	0	-9999	-10000	0	0
MAPT	-0.072	0.13	-9999	-0.31	59	59
GNA11	-0.007	0.056	-9999	-0.25	4	4
Rac1/GTP	-0.026	0.25	-9999	-1	22	22
MMP2	-0.065	0.16	-9999	-0.3	106	106

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	0.042	0.014	0.25	1	-10000	0	1
DAPP1	-0.34	0.43	-10000	0	-0.75	153	153
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.42	0.46	-10000	0	-0.86	166	166
mol:DAG	-0.13	0.16	-10000	0	-0.31	144	144
HRAS	0.02	0.001	-10000	0	-10000	0	0
RAP1A	0.02	0.001	-10000	0	-10000	0	0
ARF5/GDP	-0.005	0.12	-10000	0	-0.36	22	22
PLCG2	-0.03	0.16	-10000	0	-0.54	32	32
PLCG1	0.019	0	-10000	0	-10000	0	0
ARF5	0.019	0	-10000	0	-10000	0	0
mol:GTP	0.026	0.013	0.23	1	-10000	0	1
ARF1/GTP	0.04	0.013	0.24	1	-10000	0	1
RHOA	0.019	0	-10000	0	-10000	0	0
YES1	0.019	0	-10000	0	-10000	0	0
RAP1A/GTP	0.031	0.013	0.22	1	-10000	0	1
ADAP1	0.023	0.049	-10000	0	-0.24	12	12
ARAP3	0.026	0.013	0.23	1	-10000	0	1
INPPL1	0.019	0	-10000	0	-10000	0	0
PREX1	0.016	0.041	-10000	0	-0.54	2	2
ARHGEF6	-0.005	0.11	-10000	0	-0.54	16	16
ARHGEF7	0.019	0	-10000	0	-10000	0	0
ARF1	0.019	0	-10000	0	-10000	0	0
NRAS	0.02	0.001	-10000	0	-10000	0	0
FYN	0.019	0	-10000	0	-10000	0	0
ARF6	0.019	0	-10000	0	-10000	0	0
FGR	-0.036	0.16	-10000	0	-0.54	36	36
mol:Ca2+	-0.053	0.081	-10000	0	-0.16	61	61
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	-0.015	0.13	-10000	0	-0.54	22	22
ZAP70	-0.17	0.26	-10000	0	-0.54	126	126
mol:IP3	-0.079	0.11	-10000	0	-0.21	137	137
LYN	-0.004	0.11	-10000	0	-0.54	15	15
ARF1/GDP	-0.005	0.12	-10000	0	-0.36	22	22
RhoA/GDP	0.029	0.062	-10000	0	-0.34	2	2
PDK1/Src/Hsp90	0.037	0.019	-10000	0	-0.32	1	1
BLNK	-0.19	0.27	-10000	0	-0.54	140	140
actin cytoskeleton reorganization	0.019	0.099	-10000	0	-0.48	3	3
SRC	0.019	0	-10000	0	-10000	0	0
PLEKHA2	-0.03	0.14	-10000	0	-0.32	62	62
RAC1	0.019	0	-10000	0	-10000	0	0
PTEN	0.013	0.028	-10000	0	-0.51	1	1
HSP90AA1	0.017	0.029	-10000	0	-0.54	1	1
ARF6/GTP	0.042	0.013	0.25	1	-10000	0	1
RhoA/GTP	0.037	0.012	0.23	1	-10000	0	1
Src family/SYK family/BLNK-LAT	-0.45	0.54	-10000	0	-0.94	166	166
BLK	-0.34	0.26	-10000	0	-0.54	235	235
PDPK1	0.019	0	-10000	0	-10000	0	0
CYTH1	0.032	0.012	0.23	1	-10000	0	1
HCK	-0.028	0.16	-10000	0	-0.54	31	31
CYTH3	0.032	0.014	0.23	1	-10000	0	1
CYTH2	0.032	0.012	0.23	1	-10000	0	1
KRAS	0.019	0.014	-10000	0	-0.24	1	1
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.048	0.015	-10000	0	-10000	0	0
SGK1	0.042	0.016	-10000	0	-10000	0	0
INPP5D	-0.075	0.21	-10000	0	-0.54	62	62
mol:GDP	-0.016	0.12	-10000	0	-0.38	22	22
SOS1	0.019	0	-10000	0	-10000	0	0
SYK	-0.052	0.19	-10000	0	-0.54	47	47
ARF6/GDP	0.027	0.061	-10000	0	-0.34	2	2
mol:PI-3-4-5-P3	0	0.016	0.28	1	-10000	0	1
ARAP3/RAP1A/GTP	0.031	0.013	0.23	1	-10000	0	1
VAV1	-0.09	0.22	-10000	0	-0.54	72	72
mol:PI-3-4-P2	-0.043	0.15	-10000	0	-0.38	62	62
RAS family/GTP/PI3K Class I	0.04	0.012	-10000	0	-10000	0	0
PLEKHA1	-0.028	0.13	-10000	0	-0.32	62	62
Rac1/GDP	-0.005	0.12	-10000	0	-0.36	22	22
LAT	-0.049	0.18	-10000	0	-0.54	45	45
Rac1/GTP	-0.027	0.16	-10000	0	-0.44	35	35
ITK	-0.047	0.12	-10000	0	-0.24	105	105
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.19	0.24	-10000	0	-0.47	144	144
LCK	-0.2	0.27	-10000	0	-0.54	141	141
BTK	-0.016	0.1	-10000	0	-0.24	64	64

×

Fc-epsilon receptor I signaling in mast cells

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.019	0	-9999	-10000	0	0
LAT2	-0.063	0.24	-9999	-0.54	60	60
AP1	-0.086	0.28	-9999	-0.6	77	77
mol:PIP3	-0.082	0.27	-9999	-0.58	75	75
IKBKB	-0.04	0.15	-9999	-0.29	76	76
AKT1	0.026	0.077	-9999	-0.26	7	7
IKBKG	-0.04	0.15	-9999	-0.28	83	83
MS4A2	0.01	0.037	-9999	-0.25	7	7
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.018	0.014	-9999	-0.24	1	1
MAP3K1	-0.057	0.23	-9999	-0.51	69	69
mol:Ca2+	-0.05	0.2	-9999	-0.41	75	75
LYN	-0.005	0.11	-9999	-0.55	15	15
CBLB	-0.028	0.17	-9999	-0.45	40	40
SHC1	0.019	0	-9999	-10000	0	0
RasGAP/p62DOK	0.033	0.024	-9999	-0.29	1	1
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	-0.075	0.21	-9999	-0.54	62	62
PLD2	0.007	0.084	-9999	-0.25	31	31
PTPN13	-0.022	0.17	-9999	-0.5	30	30
PTPN11	0.016	0.011	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	0.021	0.11	-9999	-0.29	27	27
SYK	-0.054	0.19	-9999	-0.55	47	47
GRB2	0.019	0.001	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.13	0.25	-9999	-0.6	73	73
LAT	-0.061	0.22	-9999	-0.47	66	66
PAK2	-0.076	0.27	-9999	-0.59	69	69
NFATC2	-0.029	0.14	-9999	-0.56	23	23
HRAS	-0.094	0.3	-9999	-0.66	69	69
GAB2	0.015	0.03	-9999	-0.24	5	5
PLA2G1B	0.03	0.015	-9999	-10000	0	0
Fc epsilon R1	-0.006	0.11	-9999	-0.32	33	33
Antigen/IgE/Fc epsilon R1	-0.005	0.096	-9999	-0.29	33	33
mol:GDP	-0.12	0.32	-9999	-0.68	80	80
JUN	-0.007	0.078	-9999	-0.24	36	36
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.019	0.001	-9999	-10000	0	0
FOS	0.011	0.045	-9999	-0.24	11	11
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.036	0.18	-9999	-0.43	49	49
CHUK	-0.04	0.15	-9999	-0.3	74	74
KLRG1	-0.033	0.17	-9999	-0.42	46	46
VAV1	-0.077	0.25	-9999	-0.52	74	74
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.027	0.17	-9999	-0.45	40	40
negative regulation of mast cell degranulation	-0.064	0.23	-9999	-0.5	69	69
BTK	-0.13	0.35	-9999	-0.77	76	76
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.039	0.18	-9999	-0.41	50	50
GAB2/PI3K/SHP2	-0.023	0.064	-9999	-0.28	8	8
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.045	0.21	-9999	-0.45	61	61
RAF1	0.018	0.018	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.046	0.19	-9999	-0.39	75	75
FCER1G	-0.029	0.16	-9999	-0.54	31	31
FCER1A	0.005	0.058	-9999	-0.26	15	15
Antigen/IgE/Fc epsilon R1/Fyn	0.006	0.091	-9999	-0.27	33	33
MAPK3	0.029	0.016	-9999	-10000	0	0
MAPK1	0.029	0.016	-9999	-10000	0	0
NFKB1	0.019	0	-9999	-10000	0	0
MAPK8	0.01	0.072	-9999	-10000	0	0
DUSP1	0.015	0.033	-9999	-0.24	6	6
NF-kappa-B/RelA	-0.043	0.07	-9999	-0.2	38	38
actin cytoskeleton reorganization	-0.026	0.17	-9999	-0.49	34	34
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.067	0.26	-9999	-0.58	66	66
FER	-0.027	0.17	-9999	-0.44	41	41
RELA	0.019	0	-9999	-10000	0	0
ITK	-0.12	0.22	-9999	-0.46	106	106
SOS1	0.019	0	-9999	-10000	0	0
PLCG1	-0.11	0.32	-9999	-0.7	72	72
cytokine secretion	-0.032	0.051	-9999	-0.16	2	2
SPHK1	-0.031	0.17	-9999	-0.46	41	41
PTK2	-0.028	0.18	-9999	-0.53	32	32
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.13	0.26	-9999	-0.62	71	71
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.065	0.25	-9999	-0.55	70	70
MAP2K2	0.024	0.016	-9999	-10000	0	0
MAP2K1	0.024	0.016	-9999	-10000	0	0
MAP2K7	0.019	0	-9999	-10000	0	0
KLRG1/SHP2	-0.028	0.16	-9999	-0.45	35	35
MAP2K4	0.025	0.013	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.005	0.13	-9999	-0.34	41	41
mol:Choline	0.007	0.083	-9999	-0.25	31	31
SHC/Grb2/SOS1	-0.006	0.16	-9999	-0.44	36	36
FYN	0.019	0	-9999	-10000	0	0
DOK1	0.019	0	-9999	-10000	0	0
PXN	-0.018	0.16	-9999	-0.52	27	27
HCLS1	-0.073	0.25	-9999	-0.55	65	65
PRKCB	-0.073	0.2	-9999	-0.41	84	84
FCGR2B	-0.005	0.11	-9999	-0.52	16	16
IGHE	-0.001	0.007	-9999	-10000	0	0
KLRG1/SHIP	-0.067	0.24	-9999	-0.51	69	69
LCP2	-0.016	0.14	-9999	-0.54	23	23
PLA2G4A	-0.032	0.17	-9999	-0.44	45	45
RASA1	0.017	0.029	-9999	-0.54	1	1
mol:Phosphatidic acid	0.007	0.083	-9999	-0.25	31	31
IKK complex	-0.015	0.11	-9999	-0.22	67	67
WIPF1	0.011	0.064	-9999	-0.54	5	5

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.002	0.38	-9999	-0.79	43	43
HDAC7	0.021	0.004	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	0.001	0.36	-9999	-0.72	35	35
SMAD4	0.02	0	-9999	-10000	0	0
ID2	-0.002	0.38	-9999	-0.79	43	43
AP1	0.008	0.066	-9999	-0.28	7	7
ABCG2	-0.022	0.41	-9999	-0.84	47	47
HIF1A	0.026	0.074	-9999	-10000	0	0
TFF3	-0.059	0.43	-9999	-0.82	62	62
GATA2	0.016	0.036	-9999	-0.24	7	7
AKT1	0.018	0.092	-9999	-0.22	10	10
response to hypoxia	-0.001	0.094	-9999	-0.2	23	23
MCL1	-0.002	0.38	-9999	-0.79	43	43
NDRG1	-0.004	0.38	-9999	-0.8	43	43
SERPINE1	-0.01	0.39	-9999	-0.79	45	45
FECH	-0.002	0.38	-9999	-0.79	43	43
FURIN	-0.002	0.38	-9999	-0.79	43	43
NCOA2	0.02	0.014	-9999	-0.24	1	1
EP300	0.025	0.15	-9999	-0.29	33	33
HMOX1	-0.003	0.38	-9999	-0.79	43	43
BHLHE40	-0.003	0.38	-9999	-0.79	43	43
BHLHE41	-0.007	0.39	-9999	-0.81	44	44
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.084	0.11	-9999	-10000	0	0
ENG	0.074	0.093	-9999	-10000	0	0
JUN	-0.006	0.078	-9999	-0.24	36	36
RORA	-0.003	0.38	-9999	-0.78	44	44
ABCB1	-0.12	0.34	-9999	-1.3	29	29
TFRC	-0.002	0.38	-9999	-0.79	43	43
CXCR4	-0.022	0.41	-9999	-0.84	50	50
TF	-0.082	0.42	-9999	-0.84	56	56
CITED2	-0.002	0.38	-9999	-0.79	43	43
HIF1A/ARNT	-0.007	0.45	-9999	-0.89	42	42
LDHA	-0.017	0.078	-9999	-1.3	1	1
ETS1	-0.002	0.38	-9999	-0.79	43	43
PGK1	-0.002	0.38	-9999	-0.79	43	43
NOS2	-0.011	0.38	-9999	-0.8	44	44
ITGB2	-0.034	0.43	-9999	-0.87	52	52
ALDOA	-0.002	0.38	-9999	-0.79	43	43
Cbp/p300/CITED2	-0.015	0.42	-9999	-0.87	42	42
FOS	0.012	0.045	-9999	-0.24	11	11
HK2	-0.002	0.38	-9999	-0.79	43	43
SP1	0.024	0.022	-9999	-10000	0	0
GCK	-0.086	0.48	-9999	-1.3	42	42
HK1	-0.002	0.38	-9999	-0.79	43	43
NPM1	-0.002	0.38	-9999	-0.79	43	43
EGLN1	-0.002	0.38	-9999	-0.79	43	43
CREB1	0.028	0.001	-9999	-10000	0	0
PGM1	-0.002	0.38	-9999	-0.79	43	43
SMAD3	0.02	0	-9999	-10000	0	0
EDN1	0.023	0.21	-9999	-0.8	7	7
IGFBP1	-0.012	0.38	-9999	-0.8	43	43
VEGFA	0.021	0.33	-9999	-0.65	30	30
HIF1A/JAB1	0.033	0.05	-9999	-10000	0	0
CP	-0.11	0.46	-9999	-0.86	68	68
CXCL12	-0.013	0.4	-9999	-0.82	49	49
COPS5	0.02	0.001	-9999	-10000	0	0
SMAD3/SMAD4	0.031	0.001	-9999	-10000	0	0
BNIP3	-0.002	0.38	-9999	-0.79	43	43
EGLN3	-0.004	0.38	-9999	-0.79	44	44
CA9	-0.035	0.39	-9999	-0.82	46	46
TERT	-0.011	0.39	-9999	-0.79	46	46
ENO1	-0.002	0.38	-9999	-0.79	43	43
PFKL	-0.002	0.38	-9999	-0.79	43	43
NCOA1	0.019	0.001	-9999	-10000	0	0
ADM	-0.042	0.39	-9999	-0.8	49	49
ARNT	0.025	0.074	-9999	-10000	0	0
HNF4A	-0.023	0.08	-9999	-0.25	33	33
ADFP	-0.012	0.38	-9999	-0.79	44	44
SLC2A1	0.027	0.32	-9999	-0.65	29	29
LEP	-0.034	0.38	-9999	-0.81	43	43
HIF1A/ARNT/Cbp/p300	-0.01	0.37	-9999	-0.74	37	37
EPO	0.056	0.26	-9999	-0.54	6	6
CREBBP	0.025	0.15	-9999	-0.28	41	41
HIF1A/ARNT/Cbp/p300/HDAC7	0.017	0.37	-9999	-0.76	29	29
PFKFB3	-0.002	0.38	-9999	-0.79	43	43
NT5E	-0.029	0.39	-9999	-0.79	48	48

×

Ephrin A reverse signaling

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
MAPKKK cascade	-0.034	0.1	-9999	-0.33	26	26
EFNA5	0.008	0.076	-9999	-0.54	7	7
FYN	-0.024	0.092	-9999	-0.3	26	26
neuron projection morphogenesis	-0.034	0.1	-9999	-0.33	26	26
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.034	0.1	-9999	-0.33	26	26
EPHA5	-0.071	0.15	-9999	-0.3	102	102

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.026	0.03	-9999	-0.38	2	2
FBXW11	0.019	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.033	0.001	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.065	0.18	-9999	-0.46	47	47
NFKBIA	-0.1	0.2	-9999	-0.31	141	141
MAPK14	0.019	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.033	0	-9999	-10000	0	0
ARRB2	0.02	0	-9999	-10000	0	0
REL	0.019	0.001	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.031	0.026	-9999	-0.32	2	2
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.033	0	-9999	-10000	0	0
PIK3CA	0.018	0.014	-9999	-0.24	1	1
NF kappa B1 p50 dimer	0.025	0	-9999	-10000	0	0
PIK3R1	0.019	0	-9999	-10000	0	0
NFKB1	0.026	0	-9999	-10000	0	0
RELA	0.019	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	-0.079	0.16	-9999	-0.27	141	141
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	-0.059	0.17	-9999	-0.45	47	47
SRC	0.019	0	-9999	-10000	0	0
PI3K	0.028	0.009	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.08	0.16	-9999	-0.27	141	141
IKBKB	0.019	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.019	0	-9999	-10000	0	0
SYK	-0.052	0.19	-9999	-0.54	47	47
I kappa B alpha/PIK3R1	-0.086	0.19	-9999	-0.29	141	141
cell death	-0.056	0.17	-9999	-0.43	47	47
NF kappa B1 p105/c-Rel	0.033	0.001	-9999	-10000	0	0
LCK	-0.2	0.27	-9999	-0.54	141	141
BCL3	0.016	0.041	-9999	-0.54	2	2

×

Syndecan-1-mediated signaling events

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
TGFB1	0.016	0.041	-9999	-0.54	2	2
CCL5	-0.15	0.26	-9999	-0.54	110	110
SDCBP	0.019	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.06	0.17	-9999	-0.52	29	29
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.049	0.17	-9999	-0.51	29	29
Syndecan-1/Syntenin	-0.049	0.17	-9999	-0.5	29	29
MAPK3	-0.031	0.15	-9999	-0.48	25	25
HGF/MET	-0.016	0.12	-9999	-0.4	27	27
TGFB1/TGF beta receptor Type II	0.016	0.041	-9999	-0.54	2	2
BSG	0.018	0.014	-9999	-0.24	1	1
keratinocyte migration	-0.049	0.17	-9999	-0.5	29	29
Syndecan-1/RANTES	-0.13	0.23	-9999	-0.4	122	122
Syndecan-1/CD147	-0.038	0.16	-9999	-0.5	26	26
Syndecan-1/Syntenin/PIP2	-0.048	0.16	-9999	-0.48	29	29
LAMA5	0.017	0.029	-9999	-0.54	1	1
positive regulation of cell-cell adhesion	-0.047	0.16	-9999	-0.47	29	29
MMP7	-0.016	0.11	-9999	-0.33	34	34
HGF	0	0.085	-9999	-0.34	19	19
Syndecan-1/CASK	-0.059	0.16	-9999	-0.5	29	29
Syndecan-1/HGF/MET	-0.066	0.19	-9999	-0.5	43	43
regulation of cell adhesion	-0.024	0.15	-9999	-0.46	25	25
HPSE	0.019	0	-9999	-10000	0	0
positive regulation of cell migration	-0.06	0.17	-9999	-0.52	29	29
SDC1	-0.061	0.18	-9999	-0.53	29	29
Syndecan-1/Collagen	-0.06	0.17	-9999	-0.52	29	29
PPIB	0.019	0	-9999	-10000	0	0
MET	-0.024	0.14	-9999	-0.43	35	35
PRKACA	0.019	0	-9999	-10000	0	0
MMP9	-0.082	0.21	-9999	-0.52	68	68
MAPK1	-0.031	0.15	-9999	-0.48	25	25
homophilic cell adhesion	-0.059	0.17	-9999	-0.52	29	29
MMP1	-0.058	0.16	-9999	-0.35	77	77

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	-0.033	0.12	-9999	-0.27	78	78
RGS9BP	0.017	0.019	-9999	-0.24	2	2
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0	0	-9999	-10000	0	0
mol:Na +	0.001	0.023	-9999	-10000	0	0
mol:ADP	0.007	0.011	-9999	-10000	0	0
GNAT2	0.017	0.015	-9999	-0.24	1	1
RGS9-1/Gbeta5/R9AP	-0.11	0.18	-9999	-0.32	150	150
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0.013	0.021	-9999	-10000	0	0
GRK7	0.01	0.016	-9999	-0.24	1	1
CNGB3	0	0.042	-9999	-0.24	10	10
Cone Metarhodopsin II/X-Arrestin	0.002	0.01	-9999	-0.16	1	1
mol:Ca2+	-0.001	0.02	-9999	-10000	0	0
Cone PDE6	-0.091	0.15	-9999	-0.27	150	150
Cone Metarhodopsin II	0.007	0.009	-9999	-10000	0	0
Na + (4 Units)	0.001	0.02	-9999	-10000	0	0
GNAT2/GDP	-0.084	0.15	-9999	-0.26	150	150
GNB5	0.017	0.029	-9999	-0.54	1	1
mol:GMP (4 units)	0.008	0.017	-9999	-10000	0	0
Cone Transducin	-0.034	0.13	-9999	-0.29	78	78
SLC24A2	0	0	-9999	-10000	0	0
GNB3/GNGT2	-0.06	0.17	-9999	-0.38	78	78
GNB3	0.013	0.052	-9999	-0.46	4	4
GNAT2/GTP	0.012	0.01	-9999	-0.16	1	1
CNGA3	0	0	-9999	-10000	0	0
ARR3	0.003	0.015	-9999	-0.24	1	1
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	0.001	0.023	-9999	-10000	0	0
mol:Pi	-0.11	0.18	-9999	-0.32	150	150
Cone CNG Channel	0.01	0.024	-9999	-10000	0	0
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	0	0	-9999	-10000	0	0
RGS9	-0.21	0.27	-9999	-0.54	150	150
PDE6C	0	0	-9999	-10000	0	0
GNGT2	-0.095	0.22	-9999	-0.54	75	75
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.002	0.033	-9999	-0.24	6	6

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	-0.083	0.19	-9999	-0.32	128	128
BAG4	0.017	0.029	-9999	-0.54	1	1
BAD	-0.012	0.063	-9999	-0.13	53	53
NFKBIA	0.019	0	-9999	-10000	0	0
BIRC3	-0.18	0.26	-9999	-0.54	128	128
BAX	-0.012	0.063	-9999	-10000	0	0
EnzymeConsortium:3.1.4.12	-0.017	0.046	-9999	-0.097	57	57
IKBKB	-0.072	0.18	-9999	-0.4	53	53
MAP2K2	0.001	0.062	-9999	-10000	0	0
MAP2K1	0.001	0.062	-9999	-10000	0	0
SMPD1	-0.011	0.046	-9999	-10000	0	0
GO:0005551	0	0	-9999	-10000	0	0
FADD/Caspase 8	-0.073	0.18	-9999	-0.41	56	56
MAP2K4	-0.005	0.061	-9999	-10000	0	0
protein ubiquitination	-0.072	0.18	-9999	-0.39	57	57
EnzymeConsortium:2.7.1.37	0.004	0.066	-9999	-10000	0	0
response to UV	0	0.001	-9999	-0.002	53	53
RAF1	-0.005	0.063	-9999	-10000	0	0
CRADD	0.018	0.014	-9999	-0.24	1	1
mol:ceramide	-0.02	0.065	-9999	-0.14	53	53
I-kappa-B-alpha/RELA/p50/ubiquitin	0.026	0	-9999	-10000	0	0
MADD	0.019	0	-9999	-10000	0	0
MAP3K1	-0.012	0.063	-9999	-10000	0	0
TRADD	0.019	0	-9999	-10000	0	0
RELA/p50	0.019	0	-9999	-10000	0	0
MAPK3	0.005	0.061	-9999	-10000	0	0
MAPK1	0.005	0.061	-9999	-10000	0	0
p50/RELA/I-kappa-B-alpha	0.028	0	-9999	-10000	0	0
FADD	-0.083	0.19	-9999	-0.32	128	128
KSR1	-0.012	0.064	-9999	-0.13	53	53
MAPK8	0.003	0.058	-9999	-10000	0	0
TRAF2	0.019	0.001	-9999	-10000	0	0
response to radiation	0	0	-9999	-10000	0	0
CHUK	-0.072	0.18	-9999	-0.4	53	53
TNF R/SODD	0.027	0.021	-9999	-0.38	1	1
TNF	-0.095	0.22	-9999	-0.54	75	75
CYCS	-0.01	0.061	-9999	-10000	0	0
IKBKG	-0.072	0.18	-9999	-0.29	128	128
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.094	0.19	-9999	-0.34	128	128
RELA	0.019	0	-9999	-10000	0	0
RIPK1	0.019	0.001	-9999	-10000	0	0
AIFM1	-0.01	0.061	-9999	-10000	0	0
TNF/TNF R/SODD	-0.035	0.14	-9999	-0.32	76	76
TNFRSF1A	0.019	0.001	-9999	-10000	0	0
response to heat	0	0	-9999	-10000	0	0
CASP8	-0.001	0.075	-9999	-0.78	2	2
NSMAF	-0.081	0.18	-9999	-0.41	57	57
response to hydrogen peroxide	0	0.001	-9999	-0.002	53	53
BCL2	0.019	0	-9999	-10000	0	0

×

Visual signal transduction: Rods

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
mol:K +	0.019	0	-9999	-10000	0	0
GNAT1/GTP	0	0	-9999	-10000	0	0
Metarhodopsin II/Arrestin	0	0	-9999	-10000	0	0
PDE6G/GNAT1/GTP	-0.041	0.12	-9999	-0.33	57	57
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0	0	-9999	-10000	0	0
GRK1	0	0	-9999	-10000	0	0
CNG Channel	-0.086	0.15	-9999	-0.32	95	95
mol:Na +	-0.008	0.061	-9999	-0.27	10	10
mol:ADP	0	0	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.11	0.18	-9999	-0.32	150	150
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	0.004	0.066	-9999	-0.28	10	10
CNGB1	0.01	0.009	-9999	-10000	0	0
RDH5	0.008	0.066	-9999	-0.36	10	10
SAG	0	0	-9999	-10000	0	0
mol:Ca2+	0.01	0.063	-9999	-0.26	10	10
Na + (4 Units)	-0.019	0.049	-9999	-0.25	10	10
RGS9	-0.21	0.27	-9999	-0.54	150	150
GNB1/GNGT1	-0.016	0.069	-9999	-10000	0	0
GNAT1/GDP	-0.092	0.15	-9999	-0.27	150	150
GUCY2D	0.008	0.043	-9999	-0.24	10	10
GNGT1	-0.044	0.1	-9999	-0.24	75	75
GUCY2F	0	0	-9999	-10000	0	0
GNB5	0.017	0.029	-9999	-0.54	1	1
mol:GMP (4 units)	-0.069	0.18	-9999	-0.35	91	91
mol:11-cis-retinal	0.008	0.066	-9999	-0.36	10	10
mol:cGMP	0.001	0.062	-9999	-0.29	7	7
GNB1	0.019	0	-9999	-10000	0	0
Rhodopsin	0.007	0.047	-9999	-0.39	4	4
SLC24A1	0.019	0	-9999	-10000	0	0
CNGA1	0.006	0.068	-9999	-0.43	8	8
Metarhodopsin II	0	0	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	0.002	0.067	-9999	-0.31	7	7
RGS9BP	0.017	0.019	-9999	-0.24	2	2
Metarhodopsin II/Transducin	-0.008	0.036	-9999	-10000	0	0
GCAP Family/Ca ++	-0.004	0.061	-9999	-0.32	5	5
PDE6A/B	-0.046	0.15	-9999	-0.38	61	61
mol:Pi	-0.11	0.18	-9999	-0.32	150	150
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.009	0.051	-9999	-10000	0	0
PDE6B	-0.074	0.21	-9999	-0.54	61	61
PDE6A	0.011	0.038	-9999	-0.24	8	8
PDE6G	-0.068	0.2	-9999	-0.54	57	57
RHO	0	0	-9999	-10000	0	0
PDE6	-0.16	0.24	-9999	-0.36	186	186
GUCA1A	-0.027	0.094	-9999	-0.24	58	58
GC2/GCAP Family	-0.004	0.061	-9999	-0.32	5	5
GUCA1C	0	0	-9999	-10000	0	0
GUCA1B	0.011	0.064	-9999	-0.54	5	5

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	-0.036	0.16	-10000	0	-0.54	36	36
positive regulation of NF-kappaB transcription factor activity	-0.026	0.13	-10000	0	-0.39	37	37
MAP2K4	0.009	0.1	-10000	0	-0.34	18	18
IKBKB	0.019	0	-10000	0	-10000	0	0
TNFRSF10B	0.008	0.076	-10000	0	-0.54	7	7
TNFRSF10A	-0.047	0.18	-10000	0	-0.54	43	43
SMPD1	-0.003	0.073	-10000	0	-0.2	41	41
IKBKG	0.019	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	-0.002	0.074	-10000	0	-0.25	28	28
TRAIL/TRAILR2	-0.02	0.14	-10000	0	-0.4	41	41
TRAIL/TRAILR3	-0.038	0.16	-10000	0	-0.41	55	55
TRAIL/TRAILR1	-0.057	0.19	-10000	0	-0.46	64	64
TRAIL/TRAILR4	-0.026	0.13	-10000	0	-0.39	37	37
TRAIL/TRAILR1/DAP3/GTP	-0.032	0.16	-10000	0	-0.36	64	64
IKK complex	0.021	0.064	-10000	0	-10000	0	0
RIPK1	0.019	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.014	0	-10000	0	-10000	0	0
MAPK3	-0.014	0.12	-10000	0	-0.38	36	36
MAP3K1	0.002	0.11	-10000	0	-0.29	39	39
TRAILR4 (trimer)	-0.002	0.074	-10000	0	-0.25	28	28
TRADD	0.019	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	-0.046	0.18	-10000	0	-0.54	43	43
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.014	0.13	-10000	0	-0.29	64	64
CFLAR	0.019	0	-10000	0	-10000	0	0
MAPK1	-0.014	0.12	-10000	0	-0.38	36	36
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.01	0.15	-10000	0	-0.32	64	64
mol:ceramide	-0.002	0.072	-10000	0	-0.2	41	41
FADD	0.018	0.014	-10000	0	-0.24	1	1
MAPK8	0.015	0.1	-10000	0	-0.34	15	15
TRAF2	0.019	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	-0.018	0.14	-10000	0	-0.54	24	24
CHUK	0.019	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.036	0.17	-10000	0	-0.39	64	64
DAP3	0.019	0	-10000	0	-10000	0	0
CASP10	-0.033	0.17	0.26	1	-0.44	42	43
JNK cascade	-0.026	0.13	-10000	0	-0.39	37	37
TRAIL (trimer)	-0.036	0.16	-10000	0	-0.54	36	36
TNFRSF10C	-0.018	0.14	-10000	0	-0.54	24	24
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.021	0.15	-10000	0	-0.33	64	64
TRAIL/TRAILR2/FADD	-0.003	0.12	-10000	0	-0.33	41	41
cell death	-0.002	0.072	-10000	0	-0.2	41	41
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.012	0.091	-10000	0	-0.24	41	41
TRAILR2 (trimer)	0.008	0.076	-10000	0	-0.54	7	7
CASP8	0.005	0.075	-10000	0	-0.88	2	2
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.019	0.1	-10000	0	-0.27	41	41

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.15	0.3	-9999	-0.77	36	36
PCK1	-0.1	0.18	-9999	-0.59	11	11
HNF4A	-0.17	0.32	-9999	-0.88	32	32
KCNJ11	-0.19	0.38	-9999	-0.91	54	54
AKT1	-0.087	0.16	-9999	-0.36	33	33
response to starvation	-0.001	0.011	-9999	-10000	0	0
DLK1	-0.2	0.37	-9999	-0.88	53	53
NKX2-1	-0.074	0.17	-9999	-10000	0	0
ACADM	-0.15	0.3	-9999	-0.77	36	36
TAT	-0.078	0.16	-9999	-0.6	4	4
CEBPB	0.017	0.009	-9999	-10000	0	0
CEBPA	-0.029	0.16	-9999	-0.54	31	31
TTR	-0.13	0.28	-9999	-0.92	27	27
PKLR	-0.5	0.52	-9999	-0.94	204	204
APOA1	-0.18	0.34	-9999	-0.92	33	33
CPT1C	-0.16	0.33	-9999	-0.86	40	40
ALAS1	-0.051	0.16	-9999	-0.58	1	1
TFRC	-0.1	0.21	-9999	-0.67	9	9
FOXF1	-0.021	0.14	-9999	-0.5	28	28
NF1	0.027	0.003	-9999	-10000	0	0
HNF1A (dimer)	0.019	0	-9999	-10000	0	0
CPT1A	-0.15	0.3	-9999	-0.77	36	36
HMGCS1	-0.15	0.3	-9999	-0.76	38	38
NR3C1	0.019	0	-9999	-10000	0	0
CPT1B	-0.16	0.31	-9999	-0.79	40	40
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.019	0	-9999	-10000	0	0
GCK	-0.22	0.4	-9999	-0.94	66	66
CREB1	0.009	0.029	-9999	-10000	0	0
IGFBP1	-0.061	0.14	-9999	-10000	0	0
PDX1	-0.062	0.16	-9999	-10000	0	0
UCP2	-0.21	0.4	-9999	-0.96	62	62
ALDOB	-0.16	0.32	-9999	-0.8	39	39
AFP	-0.012	0.071	-9999	-10000	0	0
BDH1	-0.15	0.31	-9999	-0.79	39	39
HADH	-0.16	0.32	-9999	-0.79	41	41
F2	-0.18	0.34	-9999	-0.95	30	30
HNF1A	0.019	0	-9999	-10000	0	0
G6PC	-0.014	0.096	-9999	-10000	0	0
SLC2A2	-0.088	0.19	-9999	-0.54	3	3
INS	-0.008	0.003	-9999	-10000	0	0
FOXA1	0.007	0.054	-9999	-0.26	11	11
FOXA3	-0.026	0.13	-9999	-0.41	30	30
FOXA2	-0.19	0.37	-9999	-0.76	68	68
ABCC8	-0.17	0.32	-9999	-0.79	40	40
ALB	-0.013	0.084	-9999	-0.36	1	1

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.071	0.093	-10000	0	-0.17	171	171
TP53	-0.027	0.033	-10000	0	-10000	0	0
Senescence	-0.028	0.032	-10000	0	-10000	0	0
Apoptosis	-0.028	0.032	-10000	0	-10000	0	0
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.051	0.059	0.25	4	-0.17	2	6
MDM4	0.019	0	-10000	0	-10000	0	0

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.019	0.14	-9999	-0.49	27	27
GNB1/GNG2	-0.031	0.12	-9999	-0.38	22	22
mol:DAG	-0.024	0.11	-9999	-0.35	22	22
PLCG1	-0.024	0.11	-9999	-0.36	22	22
YES1	-0.038	0.1	-9999	-0.37	18	18
FZD3	0.019	0	-9999	-10000	0	0
FZD6	-0.01	0.12	-9999	-0.54	19	19
G protein	-0.023	0.11	-9999	-0.36	22	22
MAP3K7	-0.022	0.1	-9999	-0.35	17	17
mol:Ca2+	-0.023	0.1	-9999	-0.34	22	22
mol:IP3	-0.024	0.11	-9999	-0.35	22	22
NLK	0.012	0.01	-9999	-10000	0	0
GNB1	0.019	0	-9999	-10000	0	0
CAMK2A	-0.031	0.11	-9999	-0.36	21	21
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.048	0.11	-9999	-0.32	31	31
CSNK1A1	0.019	0	-9999	-10000	0	0
GNAS	-0.038	0.1	-9999	-0.36	19	19
GO:0007205	-0.023	0.1	-9999	-0.37	17	17
WNT6	0.008	0.052	-9999	-0.24	15	15
WNT4	-0.082	0.13	-9999	-0.24	141	141
NFAT1/CK1 alpha	-0.029	0.13	-9999	-0.36	29	29
GNG2	0.01	0.071	-9999	-0.54	6	6
WNT5A	0	0.091	-9999	-0.37	18	18
WNT11	-0.065	0.12	-9999	-0.24	117	117
CDC42	-0.03	0.099	-9999	-0.34	18	18

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.11	0.13	-9999	-0.33	58	58
SMAD6-7/SMURF1	0.036	0.021	-9999	-10000	0	0
NOG	-0.15	0.25	-9999	-0.53	112	112
SMAD9	-0.006	0.087	-9999	-0.47	10	10
SMAD4	0.019	0	-9999	-10000	0	0
SMAD5	-0.016	0.062	-9999	-0.28	3	3
BMP7/USAG1	-0.22	0.21	-9999	-0.42	168	168
SMAD5/SKI	-0.007	0.061	-9999	-0.28	2	2
SMAD1	0.036	0.014	-9999	-10000	0	0
BMP2	-0.002	0.088	-9999	-0.32	23	23
SMAD1/SMAD1/SMAD4	-0.001	0.005	-9999	-10000	0	0
BMPR1A	0.018	0.014	-9999	-0.24	1	1
BMPR1B	-0.14	0.13	-9999	-0.24	214	214
BMPR1A-1B/BAMBI	-0.059	0.09	-9999	-0.39	8	8
AHSG	-0.009	0.063	-9999	-0.24	24	24
CER1	0.002	0.03	-9999	-0.24	5	5
BMP2-4/CER1	0.006	0.078	-9999	-0.33	15	15
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.009	0.071	-9999	-0.3	7	7
BMP2-4 (homodimer)	0.003	0.088	-9999	-0.39	14	14
RGMB	0.002	0.064	-9999	-0.24	23	23
BMP6/BMPR2/BMPR1A-1B	-0.037	0.071	-9999	-0.22	3	3
RGMA	-0.006	0.082	-9999	-0.26	32	32
SMURF1	0.019	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.024	0.074	-9999	-0.3	13	13
BMP2-4/USAG1	-0.14	0.18	-9999	-0.33	157	157
SMAD6/SMURF1/SMAD5	-0.007	0.061	-9999	-0.28	2	2
SOSTDC1	-0.23	0.26	-9999	-0.48	181	181
BMP7/BMPR2/BMPR1A-1B	-0.092	0.11	-9999	-0.25	78	78
SKI	0.019	0	-9999	-10000	0	0
BMP6 (homodimer)	0.015	0.033	-9999	-0.24	6	6
HFE2	0	0	-9999	-10000	0	0
ZFYVE16	0.019	0	-9999	-10000	0	0
MAP3K7	0.019	0	-9999	-10000	0	0
BMP2-4/CHRD	0.007	0.083	-9999	-0.32	15	15
SMAD5/SMAD5/SMAD4	-0.007	0.061	-9999	-0.28	2	2
MAPK1	0.019	0	-9999	-10000	0	0
TAK1/TAB family	-0.024	0.052	-9999	-0.28	8	8
BMP7 (homodimer)	-0.091	0.16	-9999	-0.29	129	129
NUP214	0.019	0	-9999	-10000	0	0
BMP6/FETUA	0.005	0.049	-9999	-0.3	1	1
SMAD1/SKI	0.046	0.013	-9999	-10000	0	0
SMAD6	0.014	0.036	-9999	-0.24	7	7
CTDSP2	0.019	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.001	0.082	-9999	-0.32	15	15
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.02	0.13	-9999	-0.37	37	37
BMPR2 (homodimer)	0.019	0	-9999	-10000	0	0
GADD34/PP1CA	0.038	0.008	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.077	0.088	-9999	-10000	0	0
CHRDL1	-0.062	0.18	-9999	-0.39	72	72
ENDOFIN/SMAD1	0.046	0.013	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	0.059	0.019	-9999	-10000	0	0
SMAD6/SMURF1	0.019	0	-9999	-10000	0	0
BAMBI	0.007	0.081	-9999	-0.54	8	8
SMURF2	0.019	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.032	0.14	-9999	-0.36	47	47
BMP2-4/GREM1	-0.007	0.11	-9999	-0.32	34	34
SMAD7	0.019	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	0.005	0.082	-9999	-0.44	10	10
SMAD1/SMAD6	0.046	0.013	-9999	-10000	0	0
TAK1/SMAD6	0.028	0	-9999	-10000	0	0
BMP7	-0.091	0.16	-9999	-0.29	129	129
BMP6	0.015	0.033	-9999	-0.24	6	6
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.013	0.067	-9999	-0.26	13	13
PPM1A	0.019	0	-9999	-10000	0	0
SMAD1/SMURF2	0.046	0.013	-9999	-10000	0	0
SMAD7/SMURF1	0.028	0	-9999	-10000	0	0
CTDSPL	0.019	0	-9999	-10000	0	0
PPP1CA	0.019	0	-9999	-10000	0	0
XIAP	0.019	0	-9999	-10000	0	0
CTDSP1	0.019	0	-9999	-10000	0	0
PPP1R15A	0.018	0.014	-9999	-0.24	1	1
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.048	0.1	-9999	-0.32	28	28
CHRD	0.003	0.062	-9999	-0.24	22	22
BMPR2	0.019	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.029	0.077	-9999	-0.32	13	13
BMP4	0.005	0.084	-9999	-0.46	11	11
FST	-0.045	0.15	-9999	-0.36	61	61
BMP2-4/NOG	-0.093	0.17	-9999	-0.33	120	120
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.078	0.1	-9999	-0.33	21	21

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.019	0	-9999	-10000	0	0
SPHK1	0.011	0.058	-9999	-0.35	8	8
GNAI2	0.019	0	-9999	-10000	0	0
mol:S1P	0.022	0.034	-9999	-0.28	4	4
GNAO1	-0.094	0.13	-9999	-0.24	156	156
mol:Sphinganine-1-P	0.02	0.042	-9999	-0.38	3	3
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.049	0.026	-9999	-10000	0	0
GNAI3	0.019	0	-9999	-10000	0	0
G12/G13	0.028	0	-9999	-10000	0	0
S1PR3	0.014	0.052	-9999	-0.46	4	4
S1PR2	0.019	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	0.014	0.028	-9999	-0.24	4	4
S1PR5	0.008	0.052	-9999	-0.24	15	15
S1PR4	-0.16	0.26	-9999	-0.54	121	121
GNAI1	0.005	0.058	-9999	-0.24	19	19
S1P/S1P5/G12	0.033	0.037	-9999	-0.2	4	4
S1P/S1P3/Gq	-0.017	0.13	-9999	-0.27	73	73
S1P/S1P4/Gi	-0.095	0.15	-9999	-0.29	122	122
GNAQ	0.019	0	-9999	-10000	0	0
GNAZ	-0.016	0.094	-9999	-0.26	46	46
GNA14	-0.084	0.22	-9999	-0.53	69	69
GNA15	0.002	0.095	-9999	-0.54	11	11
GNA12	0.019	0	-9999	-10000	0	0
GNA13	0.019	0	-9999	-10000	0	0
GNA11	0.019	0	-9999	-10000	0	0
ABCC1	0.017	0.029	-9999	-0.54	1	1

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.014	0.099	-10000	0	-1.3	2	2
VDR	0.016	0.041	-10000	0	-0.54	2	2
FAM120B	0.019	0	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.048	0.17	-10000	0	-0.46	20	20
RXRs/LXRs/DNA/Oxysterols	-0.061	0.21	-10000	0	-0.42	75	75
MED1	0.019	0	-10000	0	-10000	0	0
mol:9cRA	-0.003	0.022	-10000	0	-10000	0	0
RARs/THRs/DNA/Src-1	0.018	0.065	-10000	0	-0.24	15	15
RXRs/NUR77	-0.031	0.15	-10000	0	-0.29	82	82
RXRs/PPAR	-0.025	0.12	-10000	0	-0.23	87	87
NCOR2	0.019	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.012	0.03	-10000	0	-0.39	2	2
RARs/VDR/DNA/Vit D3	0.031	0.063	-10000	0	-0.26	16	16
RARA	0.019	0	-10000	0	-10000	0	0
NCOA1	0.019	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.016	0.041	-10000	0	-0.54	2	2
RARs/RARs/DNA/9cRA	0.02	0.061	-10000	0	-0.28	14	14
RARG	0.019	0	-10000	0	-10000	0	0
RPS6KB1	0.028	0.052	-10000	0	-0.41	2	2
RARs/THRs/DNA/SMRT	0.018	0.065	-10000	0	-0.24	15	15
THRA	0.019	0	-10000	0	-10000	0	0
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.012	0.03	-10000	0	-0.39	2	2
RXRs/PPAR/9cRA/PGJ2/DNA	-0.045	0.15	0.3	1	-0.3	82	83
NR1H4	0	0	-10000	0	-10000	0	0
RXRs/LXRs/DNA	-0.026	0.16	-10000	0	-0.4	21	21
NR1H2	0.017	0.019	-10000	0	-10000	0	0
NR1H3	0.013	0.047	-10000	0	-0.55	2	2
RXRs/VDR/DNA/Vit D3	-0.03	0.14	-10000	0	-0.27	84	84
NR4A1	0.016	0.035	-10000	0	-0.34	3	3
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.033	0.11	-10000	0	-0.21	82	82
RXRG	-0.11	0.23	-10000	0	-0.54	82	82
RXR alpha/CCPG	0.026	0.014	-10000	0	-10000	0	0
RXRA	0.016	0.019	-10000	0	-10000	0	0
RXRB	0.016	0.022	-10000	0	-10000	0	0
THRB	-0.025	0.1	-10000	0	-0.25	59	59
PPARG	0.011	0.064	-10000	0	-0.54	5	5
PPARD	0.017	0.019	-10000	0	-0.24	2	2
TNF	-0.19	0.46	-10000	0	-1.1	75	75
mol:Oxysterols	-0.002	0.02	-10000	0	-10000	0	0
cholesterol transport	-0.06	0.21	-10000	0	-0.42	75	75
PPARA	0.019	0	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	-0.003	0.11	-10000	0	-0.52	15	15
RXRs/NUR77/BCL2	-0.027	0.12	-10000	0	-0.24	82	82
SREBF1	-0.047	0.19	-10000	0	-0.53	20	20
RXRs/RXRs/DNA/9cRA	-0.044	0.15	0.3	1	-0.3	82	83
ABCA1	-0.047	0.19	-10000	0	-0.53	20	20
RARs/THRs	0.021	0.08	-10000	0	-0.28	15	15
RXRs/FXR	-0.04	0.14	-10000	0	-0.29	82	82
BCL2	0.019	0	-10000	0	-10000	0	0

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.019	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.033	0.13	-9999	-0.29	78	78
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.002	0.043	-9999	-10000	0	0
AURKB	0.017	0.029	-9999	-0.54	1	1
AURKC	-0.098	0.23	-9999	-0.54	77	77

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.044	0.27	-9999	-0.64	33	33
CRP	-0.052	0.27	-9999	-0.63	38	38
cell cycle arrest	-0.065	0.3	-9999	-0.64	58	58
TIMP1	-0.022	0.23	-9999	-0.54	24	24
IL6ST	0.008	0.082	-9999	-0.54	8	8
Rac1/GDP	-0.03	0.19	-9999	-0.39	62	62
AP1	0.033	0.087	-9999	-10000	0	0
GAB2	0.016	0.031	-9999	-0.24	5	5
TNFSF11	-0.18	0.49	-9999	-1	85	85
HSP90B1	0.029	0.055	-9999	-10000	0	0
GAB1	0.019	0.001	-9999	-10000	0	0
MAPK14	0.031	0.12	-9999	-0.66	5	5
AKT1	0.063	0.017	-9999	-10000	0	0
FOXO1	0.067	0.016	-9999	-10000	0	0
MAP2K6	0.02	0.12	-9999	-0.34	24	24
mol:GTP	0	0.003	-9999	-10000	0	0
MAP2K4	-0.032	0.22	-9999	-0.46	56	56
MITF	0.007	0.13	-9999	-0.31	34	34
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0.019	0	-9999	-10000	0	0
A2M	0.019	0.031	-9999	-10000	0	0
CEBPB	0.025	0.008	-9999	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.028	0.064	-9999	-10000	0	0
STAT3	-0.068	0.32	-9999	-0.67	58	58
STAT1	0.003	0.071	-9999	-0.92	2	2
CEBPD	-0.046	0.28	-9999	-0.65	37	37
PIK3CA	0.02	0.014	-9999	-0.24	1	1
PI3K	0.031	0.009	-9999	-10000	0	0
JUN	-0.007	0.078	-9999	-0.24	36	36
PIAS3/MITF	0.015	0.12	-9999	-0.31	28	28
MAPK11	0.031	0.12	-9999	-0.66	5	5
STAT3 (dimer)/FOXO1	0.008	0.24	-9999	-0.51	32	32
GRB2/SOS1/GAB family	0.023	0.12	-9999	-0.48	10	10
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	0	0.14	-9999	-0.33	46	46
GRB2	0.019	0.001	-9999	-10000	0	0
JAK2	0.009	0.072	-9999	-0.5	7	7
LBP	-0.19	0.44	-9999	-0.88	94	94
PIK3R1	0.02	0	-9999	-10000	0	0
JAK1	0.02	0.006	-9999	-10000	0	0
MYC	-0.044	0.27	-9999	-0.64	36	36
FGG	-0.056	0.27	-9999	-0.64	38	38
macrophage differentiation	-0.065	0.3	-9999	-0.64	58	58
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0.026	0.11	-9999	-0.32	30	30
JUNB	-0.043	0.26	-9999	-0.62	34	34
FOS	0.011	0.045	-9999	-0.24	11	11
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	0.013	0.12	-9999	-0.36	23	23
STAT1/PIAS1	0.01	0.13	-9999	-0.35	22	22
GRB2/SOS1/GAB family/SHP2/PI3K	0.052	0.018	-9999	-10000	0	0
STAT3 (dimer)	-0.067	0.31	-9999	-0.67	58	58
PRKCD	-0.036	0.25	-9999	-0.52	58	58
IL6R	0.012	0.067	-9999	-0.56	5	5
SOCS3	0.035	0.14	-9999	-0.91	5	5
gp130 (dimer)/JAK1/JAK1/LMO4	0.032	0.062	-9999	-0.32	9	9
Rac1/GTP	-0.035	0.2	-9999	-0.41	63	63
HCK	-0.029	0.16	-9999	-0.54	31	31
MAPKKK cascade	0.04	0.054	-9999	-10000	0	0
bone resorption	-0.16	0.45	-9999	-0.93	86	86
IRF1	-0.11	0.41	-9999	-0.99	54	54
mol:GDP	-0.039	0.19	-9999	-0.39	65	65
SOS1	0.019	0.002	-9999	-10000	0	0
VAV1	-0.04	0.19	-9999	-0.39	65	65
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	0.031	0.12	-9999	-0.54	8	8
PTPN11	0.017	0.022	-9999	-10000	0	0
IL6/IL6RA	0.005	0.1	-9999	-0.39	20	20
gp130 (dimer)/TYK2/TYK2/LMO4	0.031	0.058	-9999	-0.32	9	9
gp130 (dimer)/JAK2/JAK2/LMO4	0.025	0.083	-9999	-0.39	12	12
IL6	-0.007	0.11	-9999	-0.43	22	22
PIAS3	0.019	0	-9999	-10000	0	0
PTPRE	0.007	0.07	-9999	-0.52	6	6
PIAS1	0.019	0	-9999	-10000	0	0
RAC1	0.019	0.002	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	0.012	0.094	-9999	-0.29	27	27
LMO4	0.018	0.032	-9999	-0.54	1	1
STAT3 (dimer)/PIAS3	-0.058	0.3	-9999	-0.62	57	57
MCL1	0.068	0.016	-9999	-10000	0	0

×

Arf6 signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.013	0.065	-9999	-0.32	13	13
ARNO/beta Arrestin1-2	0.032	0.027	-9999	-10000	0	0
EGFR	-0.007	0.086	-9999	-0.27	32	32
EPHA2	0.013	0.058	-9999	-0.54	4	4
USP6	0.019	0	-9999	-10000	0	0
IQSEC1	0.019	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.025	0.12	-9999	-0.38	31	31
ARRB2	0.01	0	-9999	-10000	0	0
mol:GTP	-0.021	0.066	-9999	-0.21	19	19
ARRB1	0.019	0	-9999	-10000	0	0
FBXO8	0.019	0	-9999	-10000	0	0
TSHR	-0.03	0.16	-9999	-0.53	32	32
EGF	-0.031	0.15	-9999	-0.42	41	41
somatostatin receptor activity	0	0	-9999	-0.001	33	33
ARAP2	0.007	0.081	-9999	-0.54	8	8
mol:GDP	-0.001	0.07	-9999	-0.23	20	20
mol:PI-3-4-5-P3	0	0	-9999	-0.001	23	23
ITGA2B	-0.004	0.073	-9999	-0.24	31	31
ARF6	0.019	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.045	0.034	-9999	-0.28	4	4
ADAP1	-0.001	0.1	-9999	-0.54	13	13
KIF13B	0.019	0	-9999	-10000	0	0
HGF/MET	-0.016	0.12	-9999	-0.4	27	27
PXN	0.019	0	-9999	-10000	0	0
ARF6/GTP	-0.018	0.1	-9999	-0.25	32	32
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.008	0.1	-9999	-0.32	31	31
ADRB2	0.013	0.058	-9999	-0.54	4	4
receptor agonist activity	0	0	-9999	0	34	34
actin filament binding	0	0	-9999	0	34	34
SRC	0.019	0	-9999	-10000	0	0
ITGB3	-0.033	0.14	-9999	-0.35	51	51
GNAQ	0.019	0	-9999	-10000	0	0
EFA6/PI-4-5-P2	0	0	-9999	-0.001	28	28
ARF6/GDP	-0.066	0.18	-9999	-0.3	128	128
ARF6/GDP/GULP/ACAP1	-0.077	0.18	-9999	-0.29	136	136
alphaIIb/beta3 Integrin/paxillin/GIT1	0.007	0.089	-9999	-0.28	19	19
ACAP1	-0.18	0.26	-9999	-0.54	128	128
ACAP2	0.019	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	0	0	-9999	-10000	0	0
EFNA1	0.019	0	-9999	-10000	0	0
HGF	0	0.085	-9999	-0.34	19	19
CYTH3	0.012	0.009	-9999	-0.16	1	1
CYTH2	0.013	0.002	-9999	-10000	0	0
NCK1	0.019	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	0	46	46
endosomal lumen acidification	0	0	-9999	0	40	40
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.007	0.12	-9999	-0.54	17	17
GNAQ/ARNO	0.024	0.004	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	8	8
MET	-0.024	0.14	-9999	-0.43	35	35
GNA14	-0.084	0.22	-9999	-0.53	69	69
GNA15	0.002	0.095	-9999	-0.54	11	11
GIT1	0.019	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	29	29
GNA11	0.019	0	-9999	-10000	0	0
LHCGR	0	0	-9999	-10000	0	0
AGTR1	0	0	-9999	-10000	0	0
desensitization of G-protein coupled receptor protein signaling pathway	0	0	-9999	-10000	0	0
IPCEF1/ARNO	-0.001	0.08	-9999	-0.34	2	2
alphaIIb/beta3 Integrin	-0.024	0.11	-9999	-0.36	26	26

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.015	0.03	-10000	0	-0.24	5	5
Jak2/Leptin Receptor	-0.002	0.076	0.21	1	-0.46	6	7
PTP1B/AKT1	0.021	0.043	-10000	0	-0.23	3	3
FYN	0.019	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	0.012	0.047	-10000	0	-0.26	3	3
EGFR	-0.007	0.086	-10000	0	-0.27	32	32
EGF/EGFR	-0.005	0.098	-10000	0	-0.29	30	30
CSF1	0.01	0.071	-10000	0	-0.54	6	6
AKT1	0.019	0	-10000	0	-10000	0	0
INSR	0.019	0.014	-10000	0	-0.24	1	1
PTP1B/N-cadherin	-0.02	0.1	-10000	0	-0.27	42	42
Insulin Receptor/Insulin	0.028	0.034	-10000	0	-10000	0	0
HCK	-0.028	0.16	-10000	0	-0.54	31	31
CRK	0.019	0	-10000	0	-10000	0	0
TYK2	0.019	0.044	-10000	0	-0.24	3	3
EGF	-0.031	0.15	-10000	0	-0.43	41	41
YES1	0.019	0	-10000	0	-10000	0	0
CAV1	0.018	0.06	-10000	0	-0.25	2	2
TXN	0.018	0.002	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	0.022	0.056	-10000	0	-0.23	3	3
cell migration	-0.012	0.047	0.26	3	-10000	0	3
STAT3	0.019	0.001	-10000	0	-10000	0	0
PRLR	-0.047	0.11	-10000	0	-0.24	91	91
ITGA2B	-0.005	0.073	-10000	0	-0.24	31	31
CSF1R	-0.013	0.13	-10000	0	-0.54	21	21
Prolactin Receptor/Prolactin	-0.045	0.095	-10000	0	-0.3	15	15
FGR	-0.036	0.16	-10000	0	-0.54	36	36
PTP1B/p130 Cas	0.021	0.045	-10000	0	-0.24	3	3
Crk/p130 Cas	0.032	0.044	-10000	0	-0.23	3	3
DOK1	0.026	0.041	-10000	0	-10000	0	0
JAK2	-0.009	0.078	-10000	0	-0.48	6	6
Jak2/Leptin Receptor/Leptin	0.002	0.071	-10000	0	-0.34	8	8
PIK3R1	0.019	0	-10000	0	-10000	0	0
PTPN1	0.012	0.047	-10000	0	-0.26	3	3
LYN	-0.004	0.11	-10000	0	-0.54	15	15
CDH2	-0.063	0.18	-10000	0	-0.41	69	69
SRC	0.026	0.02	-10000	0	-10000	0	0
ITGB3	-0.033	0.14	-10000	0	-0.35	51	51
CAT1/PTP1B	-0.16	0.23	-10000	0	-0.42	129	129
CAPN1	0.019	0.001	-10000	0	-10000	0	0
CSK	0.019	0	-10000	0	-10000	0	0
PI3K	0.012	0.025	-10000	0	-10000	0	0
mol:H2O2	0	0.002	-10000	0	-10000	0	0
STAT3 (dimer)	0.011	0.071	-10000	0	-0.34	7	7
negative regulation of transcription	-0.009	0.078	-10000	0	-0.48	6	6
FCGR2A	0.013	0.058	-10000	0	-0.54	4	4
FER	0.018	0.002	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.025	0.11	-10000	0	-0.36	26	26
BLK	-0.34	0.26	-10000	0	-0.54	235	235
Insulin Receptor/Insulin/Shc	0.026	0.008	-10000	0	-10000	0	0
RHOA	0.019	0.001	-10000	0	-10000	0	0
LEPR	0.018	0.001	-10000	0	-10000	0	0
BCAR1	0.019	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.019	0	-10000	0	-10000	0	0
mol:NADPH	0	0.002	-10000	0	-10000	0	0
TRPV6	-0.28	0.32	-10000	0	-0.63	133	133
PRL	-0.022	0.082	-10000	0	-0.24	44	44
SOCS3	0.006	0.13	-10000	0	-1.4	3	3
SPRY2	0.017	0.019	-10000	0	-0.24	2	2
Insulin Receptor/Insulin/IRS1	0.014	0.042	-10000	0	-10000	0	0
CSF1/CSF1R	0.012	0.098	-10000	0	-0.31	25	25
Ras protein signal transduction	0.011	0.015	-10000	0	-10000	0	0
IRS1	-0.003	0.072	-10000	0	-0.24	30	30
INS	0.001	0.001	-10000	0	-10000	0	0
LEP	-0.035	0.1	-10000	0	-0.24	70	70
STAT5B	0.008	0.052	-10000	0	-0.27	4	4
STAT5A	0.007	0.053	-10000	0	-0.27	4	4
GRB2	0.019	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.019	0.048	-10000	0	-0.24	3	3
CSN2	-0.02	0.036	-10000	0	-10000	0	0
PIK3CA	0.018	0.014	-10000	0	-0.24	1	1
LAT	-0.038	0.18	-10000	0	-0.5	45	45
YBX1	0.029	0.001	-10000	0	-10000	0	0
LCK	-0.2	0.27	-10000	0	-0.54	141	141
SHC1	0.019	0	-10000	0	-10000	0	0
NOX4	-0.04	0.12	-10000	0	-0.26	78	78

×

IFN-gamma 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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.059	0.15	-9999	-0.25	125	125
positive regulation of NF-kappaB transcription factor activity	0	0.001	-9999	-10000	0	0
CRKL	0.018	0.014	-9999	-0.24	1	1
STAT1 (dimer)/Cbp/p300	-0.051	0.17	-9999	-0.41	30	30
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.006	0.06	-9999	-0.35	6	6
antigen processing and presentation of peptide antigen via MHC class I	-0.045	0.077	-9999	-0.28	21	21
CaM/Ca2+	-0.051	0.14	-9999	-0.28	27	27
RAP1A	0.019	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.057	0.14	-9999	-0.36	21	21
AKT1	-0.039	0.12	-9999	-0.29	16	16
MAP2K1	-0.044	0.13	-9999	-0.3	16	16
MAP3K11	-0.055	0.13	-9999	-0.31	19	19
IFNGR1	0.008	0.017	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.024	0.1	-9999	-0.42	6	6
Rap1/GTP	-0.059	0.081	-9999	-0.35	3	3
CRKL/C3G	0.028	0.009	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.056	0.15	-9999	-0.26	131	131
CEBPB	0.002	0.12	-9999	-0.35	3	3
STAT3	0.019	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.11	0.31	-9999	-1.2	22	22
STAT1	-0.06	0.14	-9999	-0.36	21	21
CALM1	0.019	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.18	0.26	-9999	-0.53	128	128
PIK3CA	0.018	0.014	-9999	-0.24	1	1
STAT1 (dimer)/PIAS1	-0.047	0.14	-9999	-0.35	18	18
CEBPB/PTGES2/Cbp/p300	-0.036	0.051	-9999	-10000	0	0
mol:Ca2+	-0.06	0.14	-9999	-0.25	125	125
MAPK3	-0.019	0.12	-9999	-0.37	3	3
STAT1 (dimer)	-0.058	0.11	-9999	-0.39	21	21
MAPK1	-0.019	0.12	-9999	-0.37	3	3
JAK2	-0.001	0.074	-9999	-0.51	7	7
PIK3R1	0.019	0	-9999	-10000	0	0
JAK1	0.008	0.017	-9999	-10000	0	0
CAMK2D	0.019	0	-9999	-10000	0	0
DAPK1	0.018	0.089	-9999	-10000	0	0
SMAD7	0.012	0.064	-9999	-0.17	5	5
CBL/CRKL/C3G	-0.035	0.13	-9999	-0.29	16	16
PI3K	-0.048	0.13	-9999	-0.31	16	16
IFNG	-0.18	0.26	-9999	-0.54	128	128
apoptosis	0.006	0.081	-9999	-0.23	1	1
CAMK2G	0.019	0	-9999	-10000	0	0
STAT3 (dimer)	0.019	0	-9999	-10000	0	0
CAMK2A	-0.018	0.1	-9999	-0.28	46	46
CAMK2B	-0.011	0.1	-9999	-0.33	31	31
FRAP1	-0.038	0.12	-9999	-0.27	16	16
PRKCD	-0.038	0.12	-9999	-0.29	16	16
RAP1B	0.019	0	-9999	-10000	0	0
negative regulation of cell growth	-0.045	0.077	-9999	-0.28	21	21
PTPN2	0.019	0	-9999	-10000	0	0
EP300	0.019	0.002	-9999	-10000	0	0
IRF1	-0.077	0.23	-9999	-0.56	55	55
STAT1 (dimer)/PIASy	-0.048	0.14	-9999	-0.36	18	18
SOCS1	-0.049	0.32	-9999	-1.4	19	19
mol:GDP	-0.036	0.12	-9999	-0.28	16	16
CASP1	0.003	0.092	-9999	-0.31	20	20
PTGES2	0.019	0	-9999	-10000	0	0
IRF9	0.026	0.052	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.077	0.1	-9999	-0.3	16	16
RAP1/GDP	-0.059	0.082	-9999	-0.35	3	3
CBL	-0.056	0.13	-9999	-0.28	27	27
MAP3K1	-0.054	0.13	-9999	-0.3	21	21
PIAS1	0.019	0	-9999	-10000	0	0
PIAS4	0.019	0.002	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.045	0.077	-9999	-0.28	21	21
PTPN11	-0.066	0.14	-9999	-0.25	125	125
CREBBP	0.019	0.002	-9999	-10000	0	0
RAPGEF1	0.019	0	-9999	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.018	0.014	-10000	0	-0.24	1	1
Rac1/GDP	0.015	0.014	-10000	0	-10000	0	0
DOCK1	0.019	0	-10000	0	-10000	0	0
ITGA4	-0.043	0.18	-10000	0	-0.54	41	41
RAC1	0.019	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	-0.076	0.2	-10000	0	-0.42	84	84
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.019	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	-0.002	0.11	-10000	0	-0.32	41	41
alpha4/beta7 Integrin/Paxillin	-0.04	0.16	-10000	0	-0.32	84	84
lamellipodium assembly	0.057	0.007	-10000	0	-10000	0	0
PIK3CA	0.018	0.014	-10000	0	-0.24	1	1
PI3K	0.028	0.009	-10000	0	-10000	0	0
ARF6	0.019	0	-10000	0	-10000	0	0
TLN1	0.019	0	-10000	0	-10000	0	0
PXN	0.026	0	-10000	0	-10000	0	0
PIK3R1	0.019	0	-10000	0	-10000	0	0
ARF6/GTP	0.017	0.088	-10000	0	-0.23	41	41
cell adhesion	0.016	0.096	-10000	0	-0.25	41	41
CRKL/CBL	0.028	0.009	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.006	0.1	-10000	0	-0.28	41	41
ITGB1	0.017	0.019	-10000	0	-0.24	2	2
ITGB7	-0.063	0.2	-10000	0	-0.54	54	54
ARF6/GDP	0.015	0.014	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.033	0.18	-10000	0	-0.36	76	76
p130Cas/Crk/Dock1	0.038	0	-10000	0	-10000	0	0
VCAM1	-0.077	0.21	-10000	0	-0.54	63	63
alpha4/beta1 Integrin/Paxillin/Talin	0.018	0.098	-10000	0	-0.26	41	41
alpha4/beta1 Integrin/Paxillin/GIT1	0.018	0.098	-10000	0	-0.26	41	41
BCAR1	0.019	0	-10000	0	-10000	0	0
mol:GDP	-0.016	0.096	0.25	41	-10000	0	41
CBL	0.019	0	-10000	0	-10000	0	0
PRKACA	0.019	0	-10000	0	-10000	0	0
GIT1	0.019	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.018	0.098	-10000	0	-0.26	41	41
Rac1/GTP	0.059	0.007	-10000	0	-10000	0	0

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.005	0.12	-9999	-0.44	10	10
NF kappa B1 p50/RelA/I kappa B alpha	0.032	0.12	-9999	-0.39	10	10
alphaV/beta3 Integrin/Osteopontin/Src	-0.006	0.12	-9999	-0.37	37	37
AP1	0.009	0.13	-9999	-0.41	9	9
ILK	-0.008	0.13	-9999	-0.3	50	50
bone resorption	-0.017	0.16	-9999	-0.44	25	25
PTK2B	0.008	0.076	-9999	-0.54	7	7
PYK2/p130Cas	-0.026	0.17	-9999	-0.46	27	27
ITGAV	0.022	0.014	-9999	-0.24	1	1
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.027	0.021	-9999	-0.38	1	1
alphaV/beta3 Integrin/Osteopontin	-0.012	0.14	-9999	-0.34	52	52
MAP3K1	-0.009	0.13	-9999	-0.3	50	50
JUN	-0.007	0.079	-9999	-0.24	36	36
MAPK3	0.005	0.12	-9999	-0.45	10	10
MAPK1	0.005	0.12	-9999	-0.45	10	10
Rac1/GDP	0.014	0	-9999	-10000	0	0
NFKB1	0.019	0	-9999	-10000	0	0
MAPK8	-0.002	0.12	-9999	-0.37	15	15
ITGB3	-0.028	0.14	-9999	-0.34	51	51
NFKBIA	0.015	0.12	-9999	-0.44	10	10
FOS	0.011	0.045	-9999	-0.24	11	11
CD44	0.017	0.029	-9999	-0.54	1	1
CHUK	0.019	0	-9999	-10000	0	0
PLAU	0.021	0.13	-9999	-1.2	1	1
NF kappa B1 p50/RelA	0.035	0.11	-9999	-0.4	9	9
BCAR1	0.019	0	-9999	-10000	0	0
RELA	0.019	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.001	0.1	-9999	-0.37	20	20
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.049	0.17	-9999	-0.33	85	85
VAV3	-0.044	0.17	-9999	-0.32	85	85
MAP3K14	-0.005	0.13	-9999	-0.3	50	50
ROCK2	0.019	0	-9999	-10000	0	0
SPP1	-0.034	0.17	-9999	-0.51	39	39
RAC1	0.019	0	-9999	-10000	0	0
Rac1/GTP	-0.032	0.16	-9999	-0.42	30	30
MMP2	-0.004	0.13	-9999	-0.36	14	14

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.013	0.077	-9999	-0.34	15	15
EPHB2	-0.005	0.11	-9999	-0.54	16	16
Syndecan-2/TACI	-0.15	0.17	-9999	-0.32	182	182
LAMA1	-0.2	0.1	-9999	-0.24	302	302
Syndecan-2/alpha2 ITGB1	0.031	0.076	-9999	-0.28	17	17
HRAS	0.019	0	-9999	-10000	0	0
Syndecan-2/CASK	0.01	0.04	-9999	-0.32	4	4
ITGA5	0.015	0.03	-9999	-0.24	5	5
BAX	0.037	0.037	-9999	-10000	0	0
EPB41	0.017	0.029	-9999	-0.54	1	1
positive regulation of cell-cell adhesion	0.022	0.037	-9999	-0.28	4	4
LAMA3	0	0.1	-9999	-0.51	13	13
EZR	0.011	0.064	-9999	-0.54	5	5
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	0.019	0	-9999	-10000	0	0
Syndecan-2/MMP2	0.004	0.068	-9999	-0.3	8	8
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	0.022	0.039	-9999	-0.33	3	3
dendrite morphogenesis	0.009	0.081	-9999	-0.32	20	20
Syndecan-2/GM-CSF	0.018	0.046	-9999	-0.32	5	5
determination of left/right symmetry	0.015	0.049	-9999	-0.38	4	4
Syndecan-2/PKC delta	0.024	0.041	-9999	-0.31	4	4
GNB2L1	0.019	0	-9999	-10000	0	0
MAPK3	0.025	0.041	-9999	-0.28	5	5
MAPK1	0.025	0.041	-9999	-0.28	5	5
Syndecan-2/RACK1	0.033	0.036	-9999	-0.26	4	4
NF1	0.019	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.015	0.049	-9999	-0.38	4	4
ITGA2	0.012	0.048	-9999	-0.28	9	9
MAPK8	0.03	0.041	-9999	-0.31	4	4
Syndecan-2/alpha2/beta1 Integrin	-0.067	0.063	-9999	-0.26	14	14
Syndecan-2/Kininogen	0.009	0.047	-9999	-0.32	4	4
ITGB1	0.017	0.019	-9999	-0.24	2	2
SRC	0.035	0.033	-9999	-0.24	4	4
Syndecan-2/CASK/Protein 4.1	0.021	0.041	-9999	-0.28	5	5
extracellular matrix organization	0.022	0.048	-9999	-0.31	6	6
actin cytoskeleton reorganization	0.012	0.077	-9999	-0.34	15	15
Syndecan-2/Caveolin-2/Ras	0.035	0.038	-9999	-0.28	4	4
Syndecan-2/Laminin alpha3	0.013	0.08	-9999	-0.36	14	14
Syndecan-2/RasGAP	0.041	0.038	-9999	-0.24	5	5
alpha5/beta1 Integrin	0.025	0.029	-9999	-0.3	2	2
PRKCD	0.019	0	-9999	-10000	0	0
Syndecan-2 dimer	0.009	0.081	-9999	-0.32	20	20
GO:0007205	0.004	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.046	0.037	-9999	-0.23	5	5
RHOA	0.019	0	-9999	-10000	0	0
SDCBP	0.019	0	-9999	-10000	0	0
TNFRSF13B	-0.26	0.28	-9999	-0.54	179	179
RASA1	0.017	0.029	-9999	-0.54	1	1
alpha2/beta1 Integrin	0.022	0.039	-9999	-0.33	3	3
Syndecan-2/Synbindin	0.024	0.041	-9999	-0.31	4	4
TGFB1	0.016	0.041	-9999	-0.54	2	2
CASP3	0.03	0.037	-9999	-0.28	4	4
FN1	0	0.1	-9999	-0.51	13	13
Syndecan-2/IL8	-0.015	0.078	-9999	-0.3	9	9
SDC2	0.015	0.049	-9999	-0.38	4	4
KNG1	-0.003	0.047	-9999	-0.24	13	13
Syndecan-2/Neurofibromin	0.024	0.041	-9999	-0.31	4	4
TRAPPC4	0.019	0	-9999	-10000	0	0
CSF2	0.01	0.033	-9999	-0.39	2	2
Syndecan-2/TGFB1	0.022	0.048	-9999	-0.32	6	6
Syndecan-2/Syntenin/PI-4-5-P2	0.022	0.037	-9999	-0.28	4	4
Syndecan-2/Ezrin	0.03	0.053	-9999	-0.28	9	9
PRKACA	0.03	0.037	-9999	-0.28	4	4
angiogenesis	-0.015	0.078	-9999	-0.3	9	9
MMP2	-0.018	0.096	-9999	-0.26	49	49
IL8	-0.05	0.12	-9999	-0.25	93	93
calcineurin-NFAT signaling pathway	-0.15	0.17	-9999	-0.32	182	182

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.024	0.043	-9999	-0.38	4	4
Necdin/E2F1	0.016	0.07	-9999	-0.38	11	11
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.005	0.086	-9999	-0.3	8	8
NGF (dimer)/p75(NTR)/BEX1	-0.025	0.1	-9999	-0.29	29	29
NT-4/5 (dimer)/p75(NTR)	-0.017	0.074	-9999	-0.39	4	4
IKBKB	0.019	0	-9999	-10000	0	0
AKT1	0.013	0.063	-9999	-0.25	4	4
IKBKG	0.019	0	-9999	-10000	0	0
BDNF	-0.12	0.24	-9999	-0.54	88	88
MGDIs/NGR/p75(NTR)/LINGO1	-0.028	0.1	-9999	-0.28	30	30
FURIN	0.019	0	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.077	0.16	-9999	-0.34	93	93
LINGO1	-0.026	0.1	-9999	-0.25	61	61
Sortilin/TRAF6/NRIF	-0.004	0.029	-9999	-10000	0	0
proBDNF (dimer)	-0.12	0.24	-9999	-0.54	88	88
NTRK1	-0.001	0.1	-9999	-0.5	14	14
RTN4R	-0.007	0.089	-9999	-0.28	32	32
neuron apoptosis	-0.032	0.13	-9999	-0.37	11	11
IRAK1	0.019	0	-9999	-10000	0	0
SHC1	-0.003	0.074	-9999	-0.27	14	14
ARHGDIA	0.019	0	-9999	-10000	0	0
RhoA/GTP	0.014	0	-9999	-10000	0	0
Gamma Secretase	0.054	0.028	-9999	-0.26	3	3
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.012	0.078	-9999	-0.24	18	18
MAGEH1	0.019	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	0.002	0.095	-9999	-0.27	29	29
Mammalian IAPs/DIABLO	-0.069	0.16	-9999	-0.29	128	128
proNGF (dimer)	0.002	0.062	-9999	-0.24	22	22
MAGED1	0.019	0	-9999	-10000	0	0
APP	0.014	0.05	-9999	-0.54	3	3
NT-4/5 (dimer)	0	0	-9999	-10000	0	0
ZNF274	0.019	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	0.01	0.065	-9999	-0.22	14	14
NGF	0.002	0.062	-9999	-0.24	22	22
cell cycle arrest	0.004	0.071	-9999	-0.22	18	18
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.021	0.052	-9999	-0.23	5	5
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.001	0.063	-9999	-0.32	4	4
NCSTN	0.019	0	-9999	-10000	0	0
mol:GTP	0.002	0.077	-9999	-0.27	14	14
PSENEN	0.019	0	-9999	-10000	0	0
mol:ceramide	0.002	0.076	-9999	-0.25	19	19
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.03	0.047	-9999	-0.28	1	1
p75(NTR)/beta APP	-0.007	0.084	-9999	-0.4	7	7
BEX1	-0.03	0.099	-9999	-0.24	65	65
mol:GDP	-0.015	0.073	-9999	-0.27	14	14
NGF (dimer)	0.009	0.071	-9999	-0.3	11	11
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.014	0.097	-9999	-0.25	30	30
PIK3R1	0.019	0	-9999	-10000	0	0
RAC1/GTP	0.003	0.065	-9999	-0.22	14	14
MYD88	0.017	0.029	-9999	-0.54	1	1
CHUK	0.019	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	0.002	0.077	-9999	-0.27	14	14
RHOB	0.017	0.019	-9999	-0.24	2	2
RHOA	0.019	0	-9999	-10000	0	0
MAGE-G1/E2F1	0.028	0	-9999	-10000	0	0
NT3 (dimer)	-0.004	0.068	-9999	-0.24	27	27
TP53	-0.044	0.13	-9999	-0.25	93	93
PRDM4	0.003	0.073	-9999	-0.24	18	18
BDNF (dimer)	-0.12	0.15	-9999	-0.32	113	113
PIK3CA	0.018	0.014	-9999	-0.24	1	1
SORT1	0.013	0.058	-9999	-0.54	4	4
activation of caspase activity	0.002	0.083	-9999	-0.29	8	8
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.012	0.078	-9999	-0.24	18	18
RHOC	0.019	0	-9999	-10000	0	0
XIAP	0.019	0	-9999	-10000	0	0
MAPK10	-0.029	0.11	-9999	-0.37	7	7
DIABLO	0.019	0	-9999	-10000	0	0
SMPD2	0.002	0.076	-9999	-0.25	19	19
APH1B	0.014	0.05	-9999	-0.54	3	3
APH1A	0.019	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.002	0.084	-9999	-0.28	18	18
PSEN1	0.019	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	0.028	0	-9999	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.019	0.091	-9999	-0.34	12	12
MAPK8	-0.014	0.11	-9999	-0.37	7	7
MAPK9	-0.014	0.11	-9999	-0.37	7	7
APAF1	0.019	0	-9999	-10000	0	0
NTF3	-0.004	0.068	-9999	-0.24	27	27
NTF4	0	0	-9999	-10000	0	0
NDN	0.002	0.095	-9999	-0.54	11	11
RAC1/GDP	0.014	0	-9999	-10000	0	0
RhoA-B-C/GDP	0.021	0.061	-9999	-0.23	4	4
p75 CTF/Sortilin/TRAF6/NRIF	0.045	0.034	-9999	-0.28	4	4
RhoA-B-C/GTP	0.001	0.077	-9999	-0.26	14	14
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.046	0.14	-9999	-0.27	93	93
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.058	0.15	-9999	-0.3	93	93
PRKACB	0.018	0.014	-9999	-0.24	1	1
proBDNF (dimer)/p75 ECD	-0.071	0.18	-9999	-0.38	88	88
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.18	0.26	-9999	-0.54	128	128
BIRC2	0.014	0.052	-9999	-0.46	4	4
neuron projection morphogenesis	-0.014	0.07	-9999	-0.27	7	7
BAD	-0.014	0.11	-9999	-0.37	7	7
RIPK2	0.019	0	-9999	-10000	0	0
NGFR	-0.027	0.11	-9999	-0.26	59	59
CYCS	0.01	0.069	-9999	-0.25	8	8
ADAM17	0.019	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.015	0.072	-9999	-0.23	14	14
BCL2L11	-0.014	0.11	-9999	-0.37	7	7
BDNF (dimer)/p75(NTR)	-0.1	0.18	-9999	-0.4	90	90
PI3K	0.015	0.072	-9999	-0.23	14	14
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.012	0.078	-9999	-0.24	18	18
NDNL2	0.019	0	-9999	-10000	0	0
YWHAE	0.019	0	-9999	-10000	0	0
PRKCI	0.019	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)	-0.014	0.09	-9999	-0.33	14	14
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.012	0.078	-9999	-0.24	18	18
TRAF6	0.019	0	-9999	-10000	0	0
RAC1	0.019	0	-9999	-10000	0	0
PRKCZ	0.016	0.041	-9999	-0.54	2	2
PLG	0	0	-9999	-10000	0	0
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.06	0.14	-9999	-0.27	93	93
SQSTM1	0.019	0	-9999	-10000	0	0
NGFRAP1	-0.013	0.085	-9999	-0.24	44	44
CASP3	-0.01	0.1	-9999	-0.34	7	7
E2F1	0.019	0	-9999	-10000	0	0
CASP9	0.019	0	-9999	-10000	0	0
IKK complex	-0.011	0.047	-9999	-0.38	1	1
NGF (dimer)/TRKA	0.002	0.083	-9999	-0.38	12	12
MMP7	-0.016	0.11	-9999	-0.33	34	34
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.021	0.074	-9999	-0.26	8	8
MMP3	-0.1	0.13	-9999	-0.24	161	161
APAF-1/Caspase 9	-0.079	0.1	-9999	-0.3	28	28

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.014	0.049	-9999	-0.3	1	1
alphaV beta3 Integrin	-0.007	0.1	-9999	-0.29	32	32
PTK2	-0.063	0.15	-9999	-0.41	32	32
IGF1R	0.016	0.027	-9999	-0.24	4	4
PI4KB	0.019	0	-9999	-10000	0	0
MFGE8	0.005	0.06	-9999	-0.24	20	20
SRC	0.019	0	-9999	-10000	0	0
CDKN1B	-0.051	0.18	-9999	-0.48	49	49
VEGFA	0.004	0.061	-9999	-0.24	21	21
ILK	-0.051	0.18	-9999	-0.48	49	49
ROCK1	0.019	0	-9999	-10000	0	0
AKT1	-0.04	0.17	-9999	-0.45	48	48
PTK2B	0.001	0.088	-9999	-0.26	26	26
alphaV/beta3 Integrin/JAM-A	-0.033	0.14	-9999	-0.3	69	69
CBL	0.019	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.006	0.086	-9999	-0.32	20	20
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.03	0.055	-9999	-0.27	5	5
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.007	0.1	-9999	-0.32	12	12
alphaV/beta3 Integrin/Syndecan-1	-0.002	0.1	-9999	-0.34	26	26
PI4KA	0.018	0.014	-9999	-0.24	1	1
IGF-1R heterotetramer/IGF1/IRS1	-0.042	0.088	-9999	-0.44	8	8
PI4 Kinase	0.028	0.009	-9999	-10000	0	0
PIK3CA	0.018	0.014	-9999	-0.24	1	1
alphaV/beta3 Integrin/Osteopontin	-0.029	0.14	-9999	-0.35	52	52
RPS6KB1	0.002	0.1	-9999	-0.41	8	8
TLN1	0.019	0	-9999	-10000	0	0
MAPK3	-0.024	0.14	-9999	-0.48	24	24
GPR124	0.016	0.027	-9999	-0.24	4	4
MAPK1	-0.024	0.14	-9999	-0.48	24	24
PXN	0.019	0	-9999	-10000	0	0
PIK3R1	0.019	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.13	0.19	-9999	-0.35	151	151
cell adhesion	0.003	0.088	-9999	-0.32	19	19
ANGPTL3	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src	0.027	0.042	-9999	-0.25	1	1
IGF-1R heterotetramer	0.016	0.027	-9999	-0.24	4	4
Rac1/GDP	0.014	0	-9999	-10000	0	0
TGFBR2	0.019	0	-9999	-10000	0	0
ITGB3	-0.033	0.14	-9999	-0.35	51	51
IGF1	0.009	0.065	-9999	-0.37	9	9
RAC1	0.019	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	0.004	0.089	-9999	-0.32	20	20
apoptosis	0.018	0.014	-9999	-0.24	1	1
CD47	0.019	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	0.006	0.088	-9999	-0.31	20	20
VCL	0.019	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.036	0.11	-9999	-0.29	41	41
CSF1	0.01	0.071	-9999	-0.54	6	6
PIK3C2A	-0.051	0.18	-9999	-0.48	49	49
PI4 Kinase/Pyk2	-0.059	0.1	-9999	-0.37	17	17
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.008	0.089	-9999	-0.26	27	27
FAK1/Vinculin	-0.044	0.13	-9999	-0.34	27	27
alphaV beta3/Integrin/ppsTEM5	0.005	0.09	-9999	-0.32	20	20
RHOA	0.019	0	-9999	-10000	0	0
VTN	-0.058	0.19	-9999	-0.5	54	54
BCAR1	0.019	0	-9999	-10000	0	0
FGF2	-0.004	0.08	-9999	-0.26	30	30
F11R	0.004	0.078	-9999	-0.42	8	8
alphaV/beta3 Integrin/Lactadherin	-0.002	0.095	-9999	-0.32	23	23
alphaV/beta3 Integrin/TGFBR2	0.006	0.088	-9999	-0.31	20	20
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.043	0.042	-9999	-0.28	6	6
HSP90AA1	0.017	0.029	-9999	-0.54	1	1
alphaV/beta3 Integrin/Talin	0.007	0.08	-9999	-0.28	20	20
mol:GDP	0	0	-9999	-10000	0	0
FN1	0	0.1	-9999	-0.51	13	13
alphaV/beta3 Integrin/Pyk2	0.007	0.092	-9999	-0.26	26	26
SDC1	0.005	0.08	-9999	-0.43	11	11
VAV3	0.031	0.054	-9999	-0.29	8	8
PTPN11	0.019	0	-9999	-10000	0	0
IRS1	-0.003	0.072	-9999	-0.24	30	30
FAK1/Paxillin	-0.044	0.13	-9999	-0.35	23	23
cell migration	-0.033	0.12	-9999	-0.32	21	21
ITGAV	0.018	0.014	-9999	-0.24	1	1
PI3K	-0.02	0.13	-9999	-0.41	15	15
SPP1	-0.039	0.17	-9999	-0.52	39	39
KDR	0.014	0.036	-9999	-0.24	7	7
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.018	0.014	-9999	-0.24	1	1
COL4A3	-0.2	0.27	-9999	-0.53	144	144
angiogenesis	-0.032	0.16	-9999	-0.5	25	25
Rac1/GTP	0.039	0.05	-9999	-0.26	8	8
EDIL3	-0.055	0.12	-9999	-0.24	103	103
cell proliferation	0.006	0.087	-9999	-0.31	20	20

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.004	0.039	-9999	-0.16	19	19
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	0.014	0.037	-9999	-0.39	1	1
STXBP1	0.019	0	-9999	-10000	0	0
ACh/CHRNA1	-0.047	0.13	-9999	-0.31	64	64
RAB3GAP2/RIMS1/UNC13B	0.026	0.032	-9999	-0.32	1	1
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	0.001	0.044	-9999	-0.24	11	11
mol:ACh	-0.007	0.024	-9999	-0.076	6	6
RAB3GAP2	0.019	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	0.012	0.043	-9999	-0.27	1	1
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.047	0.13	-9999	-0.3	64	64
UNC13B	0.017	0.029	-9999	-0.54	1	1
CHRNA1	-0.066	0.19	-9999	-0.46	64	64
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.016	0.064	-9999	-0.16	51	51
SNAP25	-0.024	0.049	-9999	-0.098	110	110
VAMP2	0.008	0	-9999	-10000	0	0
SYT1	-0.02	0.097	-9999	-0.26	51	51
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	0.016	0.033	-9999	-10000	0	0
STX1A/SNAP25 fragment 1/VAMP2	0.012	0.043	-9999	-0.27	1	1

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	-0.003	0.13	-10000	0	-0.37	15	15
CRKL	0.04	0.11	-10000	0	-0.36	8	8
HRAS	-0.004	0.15	-10000	0	-0.37	37	37
mol:PIP3	0.025	0.1	0.35	1	-0.35	8	9
SPRED1	0.016	0.041	-10000	0	-0.54	2	2
SPRED2	0.019	0	-10000	0	-10000	0	0
GAB1	0.036	0.12	0.22	1	-0.39	8	9
FOXO3	0.046	0.1	0.26	1	-0.36	6	7
AKT1	0.041	0.11	0.26	1	-0.35	8	9
BAD	0.046	0.1	0.26	1	-0.36	6	7
megakaryocyte differentiation	0.008	0.13	-10000	0	-0.31	27	27
GSK3B	0.046	0.1	0.26	1	-0.36	6	7
RAF1	0.006	0.13	-10000	0	-0.32	28	28
SHC1	0.019	0	-10000	0	-10000	0	0
STAT3	0.036	0.12	-10000	0	-0.39	8	8
STAT1	0.021	0.2	-10000	0	-0.87	10	10
HRAS/SPRED1	0.005	0.13	-10000	0	-0.33	30	30
cell proliferation	0.036	0.12	-10000	0	-0.38	8	8
PIK3CA	0.018	0.014	-10000	0	-0.24	1	1
TEC	0.005	0.086	-10000	0	-0.54	9	9
RPS6KB1	0.039	0.12	0.24	1	-0.38	8	9
HRAS/SPRED2	0.007	0.13	-10000	0	-0.3	37	37
LYN/TEC/p62DOK	0.035	0.12	-10000	0	-0.38	13	13
MAPK3	0.019	0.098	-10000	0	-0.24	20	20
STAP1	-0.15	0.16	-10000	0	-0.28	191	191
GRAP2	-0.045	0.18	-10000	0	-0.54	42	42
JAK2	0.023	0.18	-10000	0	-0.68	13	13
STAT1 (dimer)	0.022	0.19	-10000	0	-0.85	10	10
mol:Gleevec	-0.002	0.005	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.015	0.14	-10000	0	-0.37	26	26
actin filament polymerization	0.03	0.12	-10000	0	-0.32	14	14
LYN	-0.004	0.11	-10000	0	-0.54	15	15
STAP1/STAT5A (dimer)	-0.13	0.18	-10000	0	-0.44	50	50
PIK3R1	0.019	0	-10000	0	-10000	0	0
CBL/CRKL/GRB2	0.056	0.1	-10000	0	-0.35	6	6
PI3K	0.054	0.11	0.24	1	-0.36	8	9
PTEN	0.017	0.029	-10000	0	-0.54	1	1
SCF/KIT/EPO/EPOR	-0.013	0.2	-10000	0	-1.1	8	8
MAPK8	0.036	0.12	-10000	0	-0.39	8	8
STAT3 (dimer)	0.036	0.12	-10000	0	-0.38	8	8
positive regulation of transcription	0.02	0.085	0.17	14	-0.2	20	34
mol:GDP	-0.019	0.16	-10000	0	-0.39	42	42
PIK3C2B	0.036	0.12	-10000	0	-0.39	8	8
CBL/CRKL	0.049	0.11	-10000	0	-0.34	8	8
FER	0.036	0.12	-10000	0	-0.35	10	10
SH2B3	0.036	0.12	-10000	0	-0.39	8	8
PDPK1	0.031	0.099	0.34	1	-0.32	8	9
SNAI2	0.033	0.12	-10000	0	-0.39	9	9
positive regulation of cell proliferation	0.033	0.16	-10000	0	-0.63	10	10
KITLG	0.018	0.035	-10000	0	-0.4	2	2
cell motility	0.033	0.16	-10000	0	-0.63	10	10
PTPN6	-0.12	0.24	-10000	0	-0.53	92	92
EPOR	0.039	0.074	-10000	0	-10000	0	0
STAT5A (dimer)	0.035	0.14	-10000	0	-0.52	10	10
SOCS1	-0.01	0.12	-10000	0	-0.54	19	19
cell migration	-0.001	0.13	0.28	33	-10000	0	33
SOS1	0.019	0	-10000	0	-10000	0	0
EPO	0.013	0.021	-10000	0	-0.24	2	2
VAV1	-0.09	0.22	-10000	0	-0.54	72	72
GRB10	0.035	0.12	-10000	0	-0.39	8	8
PTPN11	0.017	0.005	-10000	0	-10000	0	0
SCF/KIT	0.031	0.12	0.22	59	-0.36	11	70
GO:0007205	0	0.006	-10000	0	-10000	0	0
MAP2K1	0.015	0.11	-10000	0	-0.26	24	24
CBL	0.019	0	-10000	0	-10000	0	0
KIT	-0.022	0.22	-10000	0	-1.3	7	7
MAP2K2	0.015	0.11	-10000	0	-0.27	20	20
SHC/Grb2/SOS1	0.053	0.11	-10000	0	-0.35	8	8
STAT5A	0.035	0.14	-10000	0	-0.54	10	10
GRB2	0.019	0	-10000	0	-10000	0	0
response to radiation	0.033	0.12	-10000	0	-0.38	9	9
SHC/GRAP2	-0.019	0.13	-10000	0	-0.38	42	42
PTPRO	0.007	0.13	-10000	0	-0.32	27	27
SH2B2	0.03	0.12	-10000	0	-0.32	14	14
DOK1	0.019	0	-10000	0	-10000	0	0
MATK	0.001	0.13	-10000	0	-0.29	33	33
CREBBP	0.035	0.027	-10000	0	-10000	0	0
BCL2	0.04	0.071	-10000	0	-10000	0	0

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.029	0.12	-9999	-0.43	13	13
CRKL	-0.014	0.11	-9999	-0.34	7	7
mol:DAG	-0.002	0.12	-9999	-0.42	18	18
HRAS	0.013	0.1	-9999	-0.38	3	3
MAPK8	0.019	0.07	-9999	-0.31	15	15
RAP1A	-0.014	0.11	-9999	-0.34	7	7
GAB1	-0.014	0.11	-9999	-0.34	7	7
MAPK14	0.019	0.07	-9999	-0.31	15	15
EPO	0.007	0.026	-9999	-0.26	2	2
PLCG1	-0.003	0.12	-9999	-0.43	18	18
EPOR/TRPC2/IP3 Receptors	0.013	0.02	-9999	-0.24	1	1
RAPGEF1	0.019	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.028	0.041	-9999	-0.35	3	3
GAB1/SHC/GRB2/SOS1	0.008	0.1	-9999	-0.4	3	3
EPO/EPOR (dimer)	0.016	0.029	-9999	-0.19	1	1
IRS2	-0.014	0.11	-9999	-0.34	7	7
STAT1	0.006	0.13	-9999	-0.47	16	16
STAT5B	0.003	0.13	-9999	-0.42	18	18
cell proliferation	0.024	0.065	-9999	-0.28	15	15
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.079	0.14	-9999	-0.39	59	59
TEC	-0.021	0.13	-9999	-0.34	17	17
SOCS3	0.014	0.05	-9999	-0.54	3	3
STAT1 (dimer)	0.007	0.13	-9999	-0.46	16	16
JAK2	0.004	0.074	-9999	-0.51	7	7
PIK3R1	0.019	0	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2	-0.004	0.13	-9999	-0.22	95	95
EPO/EPOR	0.016	0.029	-9999	-0.19	1	1
LYN	-0.002	0.11	-9999	-0.54	15	15
TEC/VAV2	-0.011	0.13	-9999	-0.41	12	12
elevation of cytosolic calcium ion concentration	0.013	0.02	-9999	-0.24	1	1
SHC1	0.019	0	-9999	-10000	0	0
EPO/EPOR (dimer)/LYN	0.025	0.081	-9999	-0.35	15	15
mol:IP3	-0.002	0.12	-9999	-0.42	18	18
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.038	0.19	-9999	-0.43	59	59
SH2B3	0.013	0.014	-9999	-10000	0	0
NFKB1	0.019	0.07	-9999	-0.31	15	15
EPO/EPOR (dimer)/JAK2/SOCS3	0.011	0.044	-9999	-0.24	9	9
PTPN6	-0.023	0.12	-9999	-0.22	95	95
TEC/VAV2/GRB2	-0.002	0.13	-9999	-0.41	11	11
EPOR	0.013	0.02	-9999	-0.24	1	1
INPP5D	-0.075	0.21	-9999	-0.54	62	62
mol:GDP	0.007	0.11	-9999	-0.37	4	4
SOS1	0.019	0	-9999	-10000	0	0
PLCG2	-0.03	0.16	-9999	-0.54	32	32
CRKL/CBL/C3G	0.006	0.11	-9999	-0.38	4	4
VAV2	-0.016	0.12	-9999	-0.35	10	10
CBL	-0.014	0.11	-9999	-0.34	7	7
SHC/Grb2/SOS1	-0.046	0.081	-9999	-0.38	4	4
STAT5A	0.002	0.13	-9999	-0.42	19	19
GRB2	0.019	0	-9999	-10000	0	0
STAT5 (dimer)	0.02	0.13	-9999	-0.43	16	16
LYN/PLCgamma2	-0.022	0.15	-9999	-0.42	42	42
PTPN11	0.019	0	-9999	-10000	0	0
BTK	-0.062	0.2	-9999	-0.44	67	67
BCL2	0.029	0.12	-9999	-0.43	13	13

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	0.004	0.085	-10000	0	-0.32	23	23
cell-cell adhesion	0.032	0.076	0.32	8	-10000	0	8
Ephrin B/EPHB2/RasGAP	0.014	0.1	-10000	0	-0.26	40	40
ITSN1	0.019	0	-10000	0	-10000	0	0
PIK3CA	0.018	0.014	-10000	0	-0.24	1	1
SHC1	0.019	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	0.009	0.048	-10000	0	-0.26	2	2
Ephrin B1/EPHB1	0.006	0.065	-10000	0	-0.3	11	11
HRAS/GDP	-0.024	0.073	-10000	0	-0.26	25	25
Ephrin B/EPHB1/GRB7	0.005	0.1	-10000	0	-0.26	39	39
Endophilin/SYNJ1	0.003	0.091	-10000	0	-0.24	42	42
KRAS	0.018	0.014	-10000	0	-0.24	1	1
Ephrin B/EPHB1/Src	0.016	0.098	-10000	0	-0.26	34	34
endothelial cell migration	0.037	0.022	-10000	0	-10000	0	0
GRB2	0.019	0	-10000	0	-10000	0	0
GRB7	-0.003	0.067	-10000	0	-0.24	26	26
PAK1	0.008	0.098	-10000	0	-0.26	39	39
HRAS	0.019	0	-10000	0	-10000	0	0
RRAS	0.003	0.092	-10000	0	-0.24	42	42
DNM1	-0.008	0.08	-10000	0	-0.24	38	38
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	0.004	0.088	-10000	0	-0.25	34	34
lamellipodium assembly	-0.032	0.076	-10000	0	-0.32	8	8
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.018	0.074	-10000	0	-0.24	11	11
PIK3R1	0.019	0	-10000	0	-10000	0	0
EPHB2	-0.005	0.11	-10000	0	-0.54	16	16
EPHB3	0	0.067	-10000	0	-0.24	26	26
EPHB1	-0.005	0.093	-10000	0	-0.32	25	25
EPHB4	0.018	0.014	-10000	0	-0.24	1	1
mol:GDP	0.011	0.092	-10000	0	-0.27	26	26
Ephrin B/EPHB2	0.004	0.1	-10000	0	-0.26	42	42
Ephrin B/EPHB3	0.008	0.088	-10000	0	-0.27	27	27
JNK cascade	0.013	0.085	-10000	0	-0.27	25	25
Ephrin B/EPHB1	0.005	0.096	-10000	0	-0.27	34	34
RAP1/GDP	0.029	0.085	-10000	0	-0.24	24	24
EFNB2	0.012	0.041	-10000	0	-0.24	9	9
EFNB3	-0.016	0.14	-10000	0	-0.54	23	23
EFNB1	0.009	0.05	-10000	0	-0.24	14	14
Ephrin B2/EPHB1-2	0.006	0.091	-10000	0	-0.31	23	23
RAP1B	0.019	0	-10000	0	-10000	0	0
RAP1A	0.019	0	-10000	0	-10000	0	0
CDC42/GTP	-0.037	0.088	-10000	0	-0.26	41	41
Rap1/GTP	-0.031	0.075	-10000	0	-0.32	8	8
axon guidance	0.003	0.085	-10000	0	-0.32	23	23
MAPK3	0.029	0.067	-10000	0	-0.28	2	2
MAPK1	0.029	0.067	-10000	0	-0.28	2	2
Rac1/GDP	0.022	0.088	-10000	0	-0.25	25	25
actin cytoskeleton reorganization	-0.026	0.064	-10000	0	-0.3	6	6
CDC42/GDP	0.022	0.088	-10000	0	-0.25	25	25
PI3K	0.041	0.022	-10000	0	-10000	0	0
EFNA5	0.008	0.076	-10000	0	-0.54	7	7
Ephrin B2/EPHB4	0.022	0.024	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	0.009	0.087	-10000	0	-0.23	39	39
CDC42	0.019	0	-10000	0	-10000	0	0
RAS family/GTP	-0.031	0.073	-10000	0	-0.34	6	6
PTK2	0.008	0.022	-10000	0	-10000	0	0
MAP4K4	0.013	0.086	-10000	0	-0.28	25	25
SRC	0.019	0	-10000	0	-10000	0	0
KALRN	0.014	0.045	-10000	0	-0.39	4	4
Intersectin/N-WASP	0.028	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.032	0.097	-10000	0	-0.32	8	8
MAP2K1	0.023	0.07	-10000	0	-0.22	9	9
WASL	0.019	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	0.016	0.095	-10000	0	-0.3	25	25
cell migration	0.026	0.082	-10000	0	-0.23	29	29
NRAS	0.019	0	-10000	0	-10000	0	0
SYNJ1	0.003	0.092	-10000	0	-0.24	42	42
PXN	0.019	0	-10000	0	-10000	0	0
TF	-0.059	0.14	-10000	0	-0.27	97	97
HRAS/GTP	0.004	0.1	-10000	0	-0.35	8	8
Ephrin B1/EPHB1-2	0.005	0.094	-10000	0	-0.31	25	25
cell adhesion mediated by integrin	0.022	0.072	0.26	26	-10000	0	26
RAC1	0.019	0	-10000	0	-10000	0	0
mol:GTP	0.006	0.11	-10000	0	-0.26	47	47
RAC1-CDC42/GTP	-0.035	0.077	-10000	0	-0.33	9	9
RASA1	0.017	0.029	-10000	0	-0.54	1	1
RAC1-CDC42/GDP	0.029	0.085	-10000	0	-0.24	24	24
ruffle organization	0.018	0.097	-10000	0	-0.32	8	8
NCK1	0.019	0	-10000	0	-10000	0	0
receptor internalization	-0.002	0.094	-10000	0	-0.23	40	40
Ephrin B/EPHB2/KALRN	0.013	0.11	-10000	0	-0.27	42	42
ROCK1	0.015	0.043	-10000	0	-0.22	2	2
RAS family/GDP	-0.026	0.064	-10000	0	-0.29	6	6
Rac1/GTP	-0.034	0.08	-10000	0	-0.34	8	8
Ephrin B/EPHB1/Src/Paxillin	0.012	0.082	-10000	0	-0.24	32	32

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.019	0	-9999	-10000	0	0
EGFR	-0.007	0.086	-9999	-0.27	32	32
EGF/EGFR	-0.008	0.095	-9999	-0.24	46	46
EGF/EGFR dimer/SHC/GRB2/SOS1	0.016	0.093	-9999	-0.26	28	28
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.007	0.055	-9999	-0.24	17	17
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.031	0.15	-9999	-0.42	41	41
EGF/EGFR dimer/SHC	-0.008	0.1	-9999	-0.32	31	31
mol:GDP	0.012	0.09	-9999	-0.26	28	28
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.013	0.054	-9999	-0.42	5	5
GRB2/SOS1	0.028	0	-9999	-10000	0	0
HRAS/GTP	-0.026	0.066	-9999	-0.24	28	28
SHC1	0.019	0	-9999	-10000	0	0
HRAS/GDP	0.013	0.084	-9999	-0.24	28	28
FRAP1	0	0.082	-9999	-0.25	28	28
EGF/EGFR dimer	-0.025	0.12	-9999	-0.38	31	31
SOS1	0.019	0	-9999	-10000	0	0
GRB2	0.019	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	0.016	0.056	-9999	-0.35	5	5

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	0.028	0.12	-10000	0	-0.49	12	12
IHH	0.015	0.048	-10000	0	-0.23	9	9
SHH Np/Cholesterol/GAS1	0.017	0.034	-10000	0	-0.3	4	4
LRPAP1	0.019	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	-0.017	0.034	0.29	4	-10000	0	4
SMO/beta Arrestin2	0.04	0.092	-10000	0	-0.5	4	4
SMO	0.032	0.096	-10000	0	-0.53	4	4
AKT1	0.044	0.048	-10000	0	-10000	0	0
ARRB2	0.019	0	-10000	0	-10000	0	0
BOC	0.015	0.03	-10000	0	-0.24	5	5
ADRBK1	0.019	0	-10000	0	-10000	0	0
heart looping	0.032	0.095	-10000	0	-0.52	4	4
STIL	0.035	0.064	-10000	0	-0.39	3	3
DHH N/PTCH2	0.002	0.084	-10000	0	-0.38	12	12
DHH N/PTCH1	0.02	0.099	-10000	0	-0.32	15	15
PIK3CA	0.018	0.014	-10000	0	-0.24	1	1
DHH	-0.011	0.11	-10000	0	-0.36	29	29
PTHLH	0.022	0.16	-10000	0	-0.7	12	12
determination of left/right symmetry	0.032	0.095	-10000	0	-0.52	4	4
PIK3R1	0.019	0	-10000	0	-10000	0	0
skeletal system development	0.022	0.16	-10000	0	-0.69	12	12
IHH N/Hhip	0.012	0.026	-10000	0	-10000	0	0
DHH N/Hhip	-0.007	0.077	-10000	0	-0.39	11	11
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	0.032	0.095	-10000	0	-0.52	4	4
pancreas development	0	0	-10000	0	-10000	0	0
HHAT	0.017	0.032	-10000	0	-0.39	2	2
PI3K	0.028	0.009	-10000	0	-10000	0	0
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	0.014	0.052	-10000	0	-0.46	4	4
somite specification	0.032	0.095	-10000	0	-0.52	4	4
SHH Np/Cholesterol/PTCH1	0.031	0.068	-10000	0	-0.42	3	3
SHH Np/Cholesterol/PTCH2	0.017	0.03	-10000	0	-0.29	2	2
SHH Np/Cholesterol/Megalin	-0.15	0.16	-10000	0	-0.3	194	194
SHH	0.011	0.023	-10000	0	-0.39	1	1
catabolic process	0.03	0.083	-10000	0	-0.36	8	8
SMO/Vitamin D3	0.036	0.08	-10000	0	-0.52	3	3
SHH Np/Cholesterol/Hhip	0.008	0.017	-10000	0	-0.3	1	1
LRP2	-0.28	0.28	-10000	0	-0.54	194	194
receptor-mediated endocytosis	-0.083	0.15	-10000	0	-0.48	12	12
SHH Np/Cholesterol/BOC	0.019	0.023	-10000	0	-0.29	1	1
SHH Np/Cholesterol/CDO	0.02	0.018	-10000	0	-0.29	1	1
mesenchymal cell differentiation	-0.007	0.017	0.3	1	-10000	0	1
mol:Vitamin D3	0.035	0.069	-10000	0	-0.42	3	3
IHH N/PTCH2	0.021	0.045	-10000	0	-0.27	3	3
CDON	0.019	0	-10000	0	-10000	0	0
IHH N/PTCH1	0.033	0.084	-10000	0	-0.37	8	8
Megalin/LRPAP1	-0.19	0.2	-10000	0	-0.38	194	194
PTCH2	0.012	0.046	-10000	0	-0.28	8	8
SHH Np/Cholesterol	0.011	0.018	-10000	0	-0.3	1	1
PTCH1	0.03	0.083	-10000	0	-0.36	8	8
HHIP	0	0	-10000	0	-10000	0	0

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.005	0.058	-10000	0	-0.24	19	19
ANTXR2	0.012	0.051	-10000	0	-0.33	7	7
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.002	0.009	-10000	0	-0.065	3	3
monocyte activation	-0.15	0.29	-10000	0	-0.56	105	105
MAP2K2	0.015	0.005	-10000	0	-10000	0	0
MAP2K1	0.01	0.009	-10000	0	-10000	0	0
MAP2K7	0.01	0.009	-10000	0	-10000	0	0
MAP2K6	0.004	0.041	-10000	0	-0.28	7	7
CYAA	0.006	0.036	-10000	0	-0.26	3	3
MAP2K4	0.01	0.009	-10000	0	-10000	0	0
IL1B	-0.039	0.12	-10000	0	-0.28	64	64
Channel	0.014	0.041	-10000	0	-0.27	3	3
NLRP1	-0.023	0.094	-10000	0	-0.29	41	41
CALM1	0.019	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	0.014	0.012	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.002	0.009	0.065	3	-10000	0	3
MAPK3	0.01	0.009	-10000	0	-10000	0	0
MAPK1	0.01	0.009	-10000	0	-10000	0	0
PGR	0.008	0.016	-10000	0	-0.12	4	4
PA/Cellular Receptors	0.014	0.046	-10000	0	-0.3	3	3
apoptosis	-0.002	0.009	-10000	0	-0.065	3	3
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.014	0.038	-10000	0	-0.25	3	3
macrophage activation	0.016	0.009	-10000	0	-10000	0	0
TNF	-0.095	0.22	-10000	0	-0.54	75	75
VCAM1	-0.15	0.29	-10000	0	-0.57	105	105
platelet activation	0.014	0.012	-10000	0	-10000	0	0
MAPKKK cascade	-0.012	0.014	0.061	7	-10000	0	7
IL18	-0.086	0.18	-10000	0	-0.34	103	103
negative regulation of macrophage activation	-0.002	0.009	-10000	0	-0.065	3	3
LEF	-0.002	0.009	-10000	0	-0.065	3	3
CASP1	-0.018	0.081	-10000	0	-0.22	41	41
mol:cAMP	0.014	0.012	-10000	0	-10000	0	0
necrosis	-0.002	0.009	-10000	0	-0.065	3	3
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.014	0.039	-10000	0	-0.26	3	3
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Nectin adhesion pathway

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
PDGFRB	0.015	0.03	-9999	-0.24	5	5
alphaV beta3 Integrin	-0.009	0.1	-9999	-0.38	20	20
PTK2	0.018	0.079	-9999	-0.36	8	8
positive regulation of JNK cascade	-0.011	0.043	-9999	-0.28	8	8
CDC42/GDP	0.044	0.076	-9999	-0.37	8	8
Rac1/GDP	0.045	0.076	-9999	-0.37	8	8
RAP1B	0.019	0	-9999	-10000	0	0
RAP1A	0.019	0	-9999	-10000	0	0
CTNNB1	0.019	0	-9999	-10000	0	0
CDC42/GTP	-0.01	0.054	-9999	-0.34	8	8
nectin-3/I-afadin	-0.004	0.084	-9999	-0.37	10	10
RAPGEF1	0.033	0.08	-9999	-0.4	9	9
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.028	0.088	-9999	-0.45	9	9
PDGFB-D/PDGFRB	0.015	0.03	-9999	-0.24	5	5
TLN1	0.021	0.036	-9999	-10000	0	0
Rap1/GTP	-0.01	0.045	-9999	-0.29	8	8
IQGAP1	0.019	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.027	0.036	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.004	0.084	-9999	-0.37	10	10
PVR	0.017	0.029	-9999	-0.54	1	1
Necl-5(dimer)	0.017	0.029	-9999	-0.54	1	1
mol:GDP	0.039	0.088	-9999	-0.45	8	8
MLLT4	0	0.067	-9999	-0.24	26	26
PIK3CA	0.018	0.014	-9999	-0.24	1	1
PI3K	0.03	0.066	-9999	-0.26	8	8
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.014	0.05	-9999	-0.3	1	1
positive regulation of lamellipodium assembly	-0.013	0.05	-9999	-0.28	11	11
PVRL1	0.017	0.024	-9999	-0.24	3	3
PVRL3	-0.008	0.1	-9999	-0.32	29	29
PVRL2	0.019	0	-9999	-10000	0	0
PIK3R1	0.019	0	-9999	-10000	0	0
CDH1	-0.13	0.25	-9999	-0.54	101	101
CLDN1	-0.24	0.28	-9999	-0.54	173	173
JAM-A/CLDN1	-0.14	0.18	-9999	-0.31	179	179
SRC	0.021	0.095	-9999	-0.5	9	9
ITGB3	-0.033	0.14	-9999	-0.35	51	51
nectin-1(dimer)/I-afadin/I-afadin	0.014	0.05	-9999	-0.3	1	1
FARP2	0.035	0.085	-9999	-0.45	8	8
RAC1	0.019	0	-9999	-10000	0	0
CTNNA1	0.019	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.01	0.076	-9999	-0.32	11	11
nectin-1/I-afadin	0.014	0.05	-9999	-0.3	1	1
nectin-2/I-afadin	0.015	0.046	-9999	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0.026	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.01	0.074	-9999	-0.3	11	11
CDC42/GTP/IQGAP1/filamentous actin	0.026	0	-9999	-10000	0	0
F11R	0.01	0.071	-9999	-0.54	6	6
positive regulation of filopodium formation	-0.011	0.043	-9999	-0.28	8	8
alphaV/beta3 Integrin/Talin	0.015	0.075	-9999	-0.23	19	19
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.015	0.046	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.015	0.046	-9999	-10000	0	0
PIP5K1C	0.015	0.039	-9999	-0.17	8	8
VAV2	0.03	0.096	-9999	-0.45	11	11
RAP1/GDP	0.045	0.07	-9999	-0.34	8	8
ITGAV	0.018	0.014	-9999	-0.24	1	1
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.011	0.072	-9999	-0.3	10	10
nectin-3(dimer)/I-afadin/I-afadin	-0.004	0.084	-9999	-0.37	10	10
Rac1/GTP	-0.013	0.061	-9999	-0.33	11	11
PTPRM	0.007	0.043	-9999	-0.2	8	8
E-cadherin/beta catenin/alpha catenin	-0.035	0.14	-9999	-0.25	101	101
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.019	0	-9999	-10000	0	0

×

Ceramide 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
SPHK2	0.015	0.064	-10000	0	-0.38	9	9
MAP4K4	-0.082	0.19	-10000	0	-0.48	53	53
BAG4	0.017	0.029	-10000	0	-0.54	1	1
PKC zeta/ceramide	0	0.038	0.14	9	-0.29	2	11
NFKBIA	0.019	0	-10000	0	-10000	0	0
BIRC3	-0.18	0.26	-10000	0	-0.54	128	128
BAX	0.005	0.017	-10000	0	-10000	0	0
RIPK1	0.019	0	-10000	0	-10000	0	0
AKT1	0.019	0.007	-10000	0	-10000	0	0
BAD	-0.004	0.032	0.15	9	-10000	0	9
SMPD1	-0.032	0.099	-10000	0	-0.22	75	75
RB1	-0.004	0.035	0.15	9	-0.29	1	10
FADD/Caspase 8	-0.069	0.19	-10000	0	-0.46	56	56
MAP2K4	0.004	0.03	0.15	8	-10000	0	8
NSMAF	0.019	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.004	0.03	0.15	8	-10000	0	8
EGF	-0.031	0.15	-10000	0	-0.42	41	41
mol:ceramide	-0.012	0.034	0.15	9	-10000	0	9
MADD	0.019	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.015	0.064	-10000	0	-0.38	9	9
ASAH1	0.019	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.004	0.035	0.14	9	-0.29	1	10
cell proliferation	0.026	0.034	-10000	0	-0.23	3	3
BID	-0.047	0.13	-10000	0	-0.31	49	49
MAP3K1	-0.004	0.032	0.15	9	-10000	0	9
EIF2A	0.01	0.029	0.15	8	-10000	0	8
TRADD	0.019	0	-10000	0	-10000	0	0
CRADD	0.018	0.014	-10000	0	-0.24	1	1
MAPK3	0.015	0.028	0.15	8	-10000	0	8
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.015	0.028	0.15	8	-10000	0	8
Cathepsin D/ceramide	0	0.034	0.14	9	-0.12	4	13
FADD	-0.082	0.19	-10000	0	-0.48	54	54
KSR1	-0.004	0.032	0.15	9	-10000	0	9
MAPK8	0.01	0.034	0.15	8	-0.22	2	10
PRKRA	-0.004	0.032	0.15	9	-10000	0	9
PDGFA	0.004	0.088	-10000	0	-0.48	11	11
TRAF2	0.019	0	-10000	0	-10000	0	0
IGF1	0.009	0.065	-10000	0	-0.37	9	9
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.012	0.034	0.15	9	-10000	0	9
CTSD	0.016	0.027	-10000	0	-0.24	4	4
regulation of nitric oxide biosynthetic process	0.028	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	0.031	0.04	-10000	0	-0.24	3	3
PRKCD	0.019	0	-10000	0	-10000	0	0
PRKCZ	0.016	0.041	-10000	0	-0.54	2	2
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.015	0.064	-10000	0	-0.38	9	9
RelA/NF kappa B1	0.028	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	-0.004	0.11	-10000	0	-0.54	15	15
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.094	0.2	-10000	0	-0.5	57	57
TNFR1A/BAG4/TNF-alpha	-0.035	0.14	-10000	0	-0.32	76	76
mol:Sphingosine-1-phosphate	0.015	0.064	-10000	0	-0.38	9	9
MAP2K1	0.01	0.029	0.15	8	-10000	0	8
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.019	0	-10000	0	-10000	0	0
CYCS	0.001	0.023	-10000	0	-10000	0	0
TNFRSF1A	0.019	0	-10000	0	-10000	0	0
NFKB1	0.019	0	-10000	0	-10000	0	0
TNFR1A/BAG4	0.027	0.021	-10000	0	-0.38	1	1
EIF2AK2	0.004	0.03	0.15	8	-10000	0	8
TNF-alpha/TNFR1A/FAN	-0.034	0.14	-10000	0	-0.32	75	75
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	-0.03	0.12	-10000	0	-0.26	55	55
MAP2K2	0.01	0.029	0.15	8	-10000	0	8
SMPD3	-0.04	0.12	-10000	0	-0.28	53	53
TNF	-0.095	0.22	-10000	0	-0.54	75	75
PKC zeta/PAR4	0.009	0.086	-10000	0	-0.38	17	17
mol:PHOSPHOCHOLINE	-0.001	0.066	0.19	30	-10000	0	30
NF kappa B1/RelA/I kappa B alpha	0.042	0.066	-10000	0	-0.26	17	17
AIFM1	0.001	0.023	-10000	0	-10000	0	0
BCL2	0.019	0	-10000	0	-10000	0	0

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.01	0.072	-10000	0	-10000	0	0
adherens junction organization	-0.03	0.13	-10000	0	-0.31	10	10
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.007	0.084	-10000	0	-0.3	2	2
FMN1	-0.034	0.13	-10000	0	-0.34	13	13
mol:IP3	0.001	0.073	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.037	0.13	-10000	0	-0.24	101	101
CTNNB1	0.022	0.005	-10000	0	-10000	0	0
AKT1	0.001	0.086	-10000	0	-0.23	1	1
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.069	0.19	-10000	0	-0.38	101	101
CTNND1	0.019	0.001	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.027	0.12	-10000	0	-0.3	5	5
VASP	-0.028	0.12	-10000	0	-0.3	5	5
ZYX	-0.029	0.12	-10000	0	-0.23	101	101
JUB	-0.029	0.12	-10000	0	-0.31	6	6
EGFR(dimer)	-0.036	0.13	-10000	0	-0.33	20	20
E-cadherin/beta catenin-gamma catenin	-0.061	0.15	-10000	0	-0.3	101	101
mol:PI-3-4-5-P3	-0.005	0.09	-10000	0	-0.23	5	5
PIK3CA	0.019	0.014	-10000	0	-0.25	1	1
PI3K	-0.005	0.092	-10000	0	-0.24	5	5
FYN	0.014	0.063	-10000	0	-10000	0	0
mol:Ca2+	0.002	0.072	-10000	0	-10000	0	0
JUP	0.014	0.045	-10000	0	-0.24	11	11
PIK3R1	0.019	0.001	-10000	0	-10000	0	0
mol:DAG	0.001	0.073	-10000	0	-10000	0	0
CDH1	-0.13	0.25	-10000	0	-0.54	101	101
RhoA/GDP	0.007	0.084	-10000	0	-0.3	2	2
establishment of polarity of embryonic epithelium	-0.027	0.12	-10000	0	-0.3	5	5
SRC	0.019	0	-10000	0	-10000	0	0
RAC1	0.019	0	-10000	0	-10000	0	0
RHOA	0.019	0	-10000	0	-10000	0	0
EGFR	-0.007	0.086	-10000	0	-0.27	32	32
CASR	0.002	0.069	-10000	0	-10000	0	0
RhoA/GTP	0.01	0.068	-10000	0	-10000	0	0
AKT2	0.001	0.086	-10000	0	-10000	0	0
actin cable formation	-0.027	0.13	-10000	0	-0.37	9	9
apoptosis	0	0.082	0.22	1	-10000	0	1
CTNNA1	0.019	0.001	-10000	0	-10000	0	0
mol:GDP	-0.003	0.087	-10000	0	-0.33	2	2
PIP5K1A	-0.028	0.12	-10000	0	-0.3	5	5
PLCG1	0.001	0.074	-10000	0	-10000	0	0
Rac1/GTP	-0.027	0.12	-10000	0	-0.3	20	20
homophilic cell adhesion	0	0.002	-10000	0	-10000	0	0

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.007	0.058	0.22	4	-10000	0	4
GNAI2	0.019	0	-10000	0	-10000	0	0
S1P/S1P5/G12	0.019	0.03	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.094	0.13	-10000	0	-0.24	156	156
RhoA/GTP	-0.007	0.06	-10000	0	-0.23	4	4
negative regulation of cAMP metabolic process	-0.017	0.064	-10000	0	-0.24	5	5
GNAZ	-0.016	0.094	-10000	0	-0.26	46	46
GNAI3	0.019	0	-10000	0	-10000	0	0
GNA12	0.019	0	-10000	0	-10000	0	0
S1PR5	0.008	0.052	-10000	0	-0.24	15	15
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.017	0.065	-10000	0	-0.24	5	5
RhoA/GDP	0.014	0	-10000	0	-10000	0	0
RHOA	0.019	0	-10000	0	-10000	0	0
GNAI1	0.005	0.058	-10000	0	-0.24	19	19

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.023	0.081	-10000	0	-0.27	24	24
ER alpha/Gai/GDP/Gbeta gamma	-0.007	0.09	-10000	0	-0.4	10	10
AKT1	0.023	0.12	-10000	0	-0.79	7	7
PIK3CA	0.018	0.014	-10000	0	-0.24	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	0.019	0.12	-10000	0	-0.81	7	7
mol:Ca2+	-0.052	0.19	-10000	0	-0.4	73	73
IGF1R	0.016	0.027	-10000	0	-0.24	4	4
E2/ER alpha (dimer)/Striatin	0.019	0.048	-10000	0	-0.32	7	7
SHC1	0.019	0	-10000	0	-10000	0	0
apoptosis	-0.023	0.11	0.75	7	-10000	0	7
RhoA/GTP	-0.004	0.031	-10000	0	-0.22	7	7
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.01	0.073	-10000	0	-0.41	9	9
regulation of stress fiber formation	-0.047	0.031	-10000	0	-10000	0	0
E2/ERA-ERB (dimer)	0.007	0.078	-10000	0	-0.32	19	19
KRAS	0.018	0.014	-10000	0	-0.24	1	1
G13/GTP	0.018	0.044	-10000	0	-0.29	7	7
pseudopodium formation	0.047	0.031	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1	0.019	0.048	-10000	0	-0.32	7	7
GRB2	0.019	0	-10000	0	-10000	0	0
GNG2	0.01	0.071	-10000	0	-0.54	6	6
GNAO1	-0.094	0.13	-10000	0	-0.24	156	156
HRAS	0.019	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.013	0.094	-10000	0	-0.5	8	8
E2/ER beta (dimer)	0	0.073	-10000	0	-0.36	14	14
mol:GDP	-0.017	0.071	-10000	0	-0.32	19	19
mol:NADP	0.013	0.094	-10000	0	-0.5	8	8
PIK3R1	0.019	0	-10000	0	-10000	0	0
mol:IP3	-0.055	0.2	-10000	0	-0.42	73	73
IGF-1R heterotetramer	0.016	0.027	-10000	0	-0.24	4	4
PLCB1	-0.055	0.19	-10000	0	-0.42	69	69
PLCB2	-0.054	0.2	-10000	0	-0.42	71	71
IGF1	0.009	0.065	-10000	0	-0.37	9	9
mol:L-citrulline	0.013	0.094	-10000	0	-0.5	8	8
RHOA	0.019	0	-10000	0	-10000	0	0
Gai/GDP	-0.023	0.081	-10000	0	-0.5	2	2
JNK cascade	0	0.073	-10000	0	-0.36	14	14
BCAR1	0.019	0	-10000	0	-10000	0	0
ESR2	-0.001	0.1	-10000	0	-0.5	14	14
GNAQ	0.019	0	-10000	0	-10000	0	0
ESR1	0.008	0.076	-10000	0	-0.54	7	7
Gq family/GDP/Gbeta gamma	-0.012	0.14	-10000	0	-0.56	11	11
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.034	0.042	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.01	0.073	-10000	0	-0.41	9	9
GNAZ	-0.016	0.094	-10000	0	-0.26	46	46
E2/ER alpha (dimer)	0.006	0.055	-10000	0	-0.39	7	7
STRN	0.019	0	-10000	0	-10000	0	0
GNAL	-0.02	0.1	-10000	0	-0.27	49	49
PELP1	0.019	0	-10000	0	-10000	0	0
MAPK11	0.01	0.062	-10000	0	-0.32	12	12
GNAI2	0.019	0	-10000	0	-10000	0	0
GNAI3	0.019	0	-10000	0	-10000	0	0
GNAI1	0.005	0.058	-10000	0	-0.24	19	19
HBEGF	-0.023	0.1	-10000	0	-0.37	12	12
cAMP biosynthetic process	-0.01	0.08	-10000	0	-0.27	25	25
SRC	0.001	0.086	-10000	0	-0.39	9	9
PI3K	0.028	0.009	-10000	0	-10000	0	0
GNB1	0.019	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	0.027	0.08	-10000	0	-0.28	19	19
SOS1	0.019	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.013	0.062	-10000	0	-0.35	9	9
Gs family/GTP	-0.006	0.083	-10000	0	-0.27	25	25
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.036	0.007	-10000	0	-10000	0	0
vasodilation	0.014	0.091	-10000	0	-0.48	8	8
mol:DAG	-0.055	0.2	-10000	0	-0.42	73	73
Gs family/GDP/Gbeta gamma	-0.025	0.073	-10000	0	-0.37	8	8
MSN	0.048	0.033	-10000	0	-10000	0	0
Gq family/GTP	-0.055	0.19	-10000	0	-0.43	67	67
mol:PI-3-4-5-P3	0.02	0.11	-10000	0	-0.78	7	7
NRAS	0.019	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.014	0.091	0.48	8	-10000	0	8
GRB2/SOS1	0.028	0	-10000	0	-10000	0	0
RhoA/GDP	0.025	0.076	-10000	0	-0.3	19	19
NOS3	0.013	0.098	-10000	0	-0.53	8	8
GNA11	0.019	0	-10000	0	-10000	0	0
MAPKKK cascade	0.031	0.094	-10000	0	-0.59	7	7
E2/ER alpha (dimer)/PELP1/Src	0.015	0.088	-10000	0	-0.43	9	9
ruffle organization	0.047	0.031	-10000	0	-10000	0	0
ROCK2	0.044	0.035	-10000	0	-10000	0	0
GNA14	-0.084	0.22	-10000	0	-0.53	69	69
GNA15	0.002	0.095	-10000	0	-0.54	11	11
GNA13	0.019	0	-10000	0	-10000	0	0
MMP9	-0.04	0.14	-10000	0	-0.33	46	46
MMP2	-0.007	0.089	-10000	0	-0.37	9	9

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.019	0	-9999	-10000	0	0
SVIL	0.017	0.029	-9999	-0.54	1	1
ZNF318	0.019	0	-9999	-10000	0	0
JMJD2C	-0.005	0.026	-9999	-0.064	60	60
T-DHT/AR/Ubc9	-0.037	0.083	-9999	-0.18	44	44
CARM1	0.019	0	-9999	-10000	0	0
PRDX1	0.011	0.064	-9999	-0.54	5	5
PELP1	0.019	0	-9999	-10000	0	0
CTNNB1	0.019	0	-9999	-10000	0	0
AKT1	0.019	0	-9999	-10000	0	0
PTK2B	0.008	0.076	-9999	-0.54	7	7
MED1	0.019	0	-9999	-10000	0	0
MAK	0.015	0.031	-9999	-0.24	5	5
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	0.016	0.027	-9999	-0.24	4	4
GSN	0.018	0.014	-9999	-0.24	1	1
NCOA2	0.018	0.014	-9999	-0.24	1	1
NCOA6	0.019	0	-9999	-10000	0	0
DNA-PK	0.038	0	-9999	-10000	0	0
NCOA4	0.019	0	-9999	-10000	0	0
PIAS3	0.019	0	-9999	-10000	0	0
cell proliferation	-0.007	0.026	-9999	-0.2	1	1
XRCC5	0.019	0	-9999	-10000	0	0
UBE3A	0.019	0	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.05	0.1	-9999	-0.22	57	57
FHL2	-0.003	0.14	-9999	-1.1	6	6
RANBP9	0.019	0	-9999	-10000	0	0
JMJD1A	0.001	0.046	-9999	-0.12	41	41
CDK6	0.014	0.052	-9999	-0.46	4	4
TGFB1I1	0.017	0.032	-9999	-0.39	2	2
T-DHT/AR/CyclinD1	-0.042	0.087	-9999	-0.19	50	50
XRCC6	0.019	0	-9999	-10000	0	0
T-DHT/AR	-0.036	0.11	-9999	-0.24	45	45
CTDSP1	0.019	0	-9999	-10000	0	0
CTDSP2	0.019	0	-9999	-10000	0	0
BRCA1	0.019	0	-9999	-10000	0	0
TCF4	0.011	0.057	-9999	-0.37	7	7
CDKN2A	-0.11	0.14	-9999	-0.25	171	171
SRF	0.026	0.017	-9999	-10000	0	0
NKX3-1	-0.054	0.24	-9999	-0.7	33	33
KLK3	0.011	0.017	-9999	-10000	0	0
TMF1	0.019	0	-9999	-10000	0	0
HNRNPA1	0.019	0	-9999	-10000	0	0
AOF2	0	0	-9999	-10000	0	0
APPL1	0.026	0	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.039	0.087	-9999	-0.23	23	23
AR	-0.09	0.13	-9999	-0.25	143	143
UBA3	0.019	0	-9999	-10000	0	0
PATZ1	0.019	0	-9999	-10000	0	0
PAWR	-0.004	0.11	-9999	-0.54	15	15
PRKDC	0.019	0	-9999	-10000	0	0
PA2G4	0.019	0	-9999	-10000	0	0
UBE2I	0.019	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.032	0.076	-9999	-0.19	21	21
RPS6KA3	0.019	0	-9999	-10000	0	0
T-DHT/AR/ARA70	-0.037	0.083	-9999	-0.18	44	44
LATS2	0.019	0	-9999	-10000	0	0
T-DHT/AR/PRX1	-0.037	0.081	-9999	-0.18	49	49
Cyclin D3/CDK11 p58	0.014	0	-9999	-10000	0	0
VAV3	0.007	0.065	-9999	-0.31	13	13
KLK2	-0.047	0.11	-9999	-0.31	25	25
CASP8	0.016	0.041	-9999	-0.54	2	2
T-DHT/AR/TIF2/CARM1	-0.022	0.078	-9999	-0.19	19	19
TMPRSS2	-0.048	0.22	-9999	-0.95	17	17
CCND1	0.01	0.049	-9999	-0.24	13	13
PIAS1	0.019	0	-9999	-10000	0	0
mol:T-DHT	-0.005	0.025	-9999	-0.064	44	44
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.019	0	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.041	0.088	-9999	-0.19	47	47
CMTM2	0.007	0.05	-9999	-0.24	14	14
SNURF	-0.001	0.1	-9999	-0.54	13	13
ZMIZ1	0.015	0.024	-9999	-10000	0	0
CCND3	0.019	0	-9999	-10000	0	0
TGIF1	0.019	0	-9999	-10000	0	0
FKBP4	0.018	0.014	-9999	-0.24	1	1

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.003	0.1	-10000	0	-0.38	22	22
CRKL	0.017	0.079	-10000	0	-0.26	23	23
mol:PIP3	-0.018	0.028	0.51	1	-10000	0	1
AKT1	0.001	0.019	0.36	1	-10000	0	1
PTK2B	0.008	0.076	-10000	0	-0.54	7	7
RAPGEF1	0.024	0.076	-10000	0	-0.32	4	4
RANBP10	0.019	0	-10000	0	-10000	0	0
PIK3CA	0.018	0.014	-10000	0	-0.24	1	1
HGF/MET/SHIP2	0.001	0.1	-10000	0	-0.33	27	27
MAP3K5	-0.013	0.14	-10000	0	-0.37	28	28
HGF/MET/CIN85/CBL/ENDOPHILINS	0.014	0.095	-10000	0	-0.3	27	27
AP1	-0.003	0.065	-10000	0	-0.25	10	10
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.019	0	-10000	0	-10000	0	0
apoptosis	0.003	0.055	-10000	0	-10000	0	0
STAT3 (dimer)	0.016	0.091	-10000	0	-0.47	4	4
GAB1/CRKL/SHP2/PI3K	0.041	0.075	-10000	0	-0.36	2	2
INPP5D	-0.075	0.21	-10000	0	-0.54	62	62
CBL/CRK	0.027	0.077	-10000	0	-0.32	4	4
PTPN11	0.019	0	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.019	0	-10000	0	-10000	0	0
PTEN	0.017	0.029	-10000	0	-0.54	1	1
ELK1	-0.017	0.049	-10000	0	-0.2	22	22
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	0.019	0.051	-10000	0	-0.24	3	3
PAK1	0.008	0.019	0.34	1	-10000	0	1
HGF/MET/RANBP10	0.001	0.1	-10000	0	-0.33	27	27
HRAS	-0.005	0.16	-10000	0	-0.61	22	22
DOCK1	0.024	0.076	-10000	0	-0.32	4	4
GAB1	0.011	0.083	-10000	0	-0.28	23	23
CRK	0.018	0.079	-10000	0	-0.26	23	23
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.009	0.16	-10000	0	-0.55	27	27
JUN	-0.007	0.078	-10000	0	-0.24	36	36
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.008	0.075	-10000	0	-0.26	27	27
PIK3R1	0.019	0	-10000	0	-10000	0	0
cell morphogenesis	0.041	0.092	-10000	0	-0.43	4	4
GRB2/SHC	0.015	0.07	-10000	0	-0.23	22	22
FOS	0.011	0.045	-10000	0	-0.24	11	11
GLMN	-0.003	0.027	-10000	0	-0.26	4	4
cell motility	-0.017	0.049	-10000	0	-0.2	22	22
HGF/MET/MUC20	-0.012	0.1	-10000	0	-0.34	27	27
cell migration	0.015	0.069	-10000	0	-0.23	22	22
GRB2	0.019	0	-10000	0	-10000	0	0
CBL	0.019	0	-10000	0	-10000	0	0
MET/RANBP10	-0.003	0.1	-10000	0	-0.38	22	22
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.011	0.092	-10000	0	-0.26	33	33
MET/MUC20	-0.017	0.1	-10000	0	-0.3	35	35
RAP1B	0.03	0.072	-10000	0	-0.32	3	3
RAP1A	0.03	0.072	-10000	0	-0.32	3	3
HGF/MET/RANBP9	0.001	0.1	-10000	0	-0.33	27	27
RAF1	0.003	0.15	-10000	0	-0.57	22	22
STAT3	0.016	0.092	-10000	0	-0.48	4	4
cell proliferation	0.019	0.12	-10000	0	-0.37	27	27
RPS6KB1	0.006	0.034	-10000	0	-0.19	2	2
MAPK3	-0.023	0.044	-10000	0	-10000	0	0
MAPK1	-0.023	0.044	-10000	0	-10000	0	0
RANBP9	0.019	0	-10000	0	-10000	0	0
MAPK8	0.017	0.11	-10000	0	-0.33	14	14
SRC	0.017	0.087	-10000	0	-0.44	4	4
PI3K	0.015	0.07	-10000	0	-0.23	22	22
MET/Glomulin	-0.012	0.092	-10000	0	-0.26	38	38
SOS1	0.019	0	-10000	0	-10000	0	0
MAP2K1	0.011	0.14	-10000	0	-0.52	22	22
MET	-0.024	0.14	-10000	0	-0.43	35	35
MAP4K1	-0.02	0.14	-10000	0	-0.38	27	27
PTK2	0.019	0	-10000	0	-10000	0	0
MAP2K2	0.011	0.14	-10000	0	-0.52	22	22
BAD	0.008	0.018	0.34	1	-10000	0	1
MAP2K4	-0.004	0.13	-10000	0	-0.36	22	22
SHP2/GRB2/SOS1/GAB1	-0.025	0.083	-10000	0	-0.34	22	22
INPPL1	0.019	0	-10000	0	-10000	0	0
PXN	0.019	0	-10000	0	-10000	0	0
SH3KBP1	0.019	0	-10000	0	-10000	0	0
HGS	0	0.07	-10000	0	-0.23	27	27
PLCgamma1/PKC	0.014	0	-10000	0	-10000	0	0
HGF	0	0.085	-10000	0	-0.34	19	19
RASA1	0.017	0.029	-10000	0	-0.54	1	1
NCK1	0.019	0	-10000	0	-10000	0	0
PTPRJ	0.019	0	-10000	0	-10000	0	0
NCK/PLCgamma1	0.017	0.071	-10000	0	-0.22	27	27
PDPK1	-0.008	0.022	0.4	1	-10000	0	1
HGF/MET/SHIP	-0.058	0.17	-10000	0	-0.37	78	78

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.012	0.041	-10000	0	-0.24	9	9
EPHB2	-0.006	0.12	-10000	0	-0.54	16	16
EFNB1	-0.001	0.068	-10000	0	-0.31	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.003	0.12	-10000	0	-0.3	41	41
Ephrin B2/EPHB1-2	0.005	0.093	-10000	0	-0.32	23	23
neuron projection morphogenesis	-0.025	0.11	-10000	0	-0.29	41	41
Ephrin B1/EPHB1-2/Tiam1	-0.012	0.13	-10000	0	-0.33	41	41
DNM1	-0.009	0.08	-10000	0	-0.24	38	38
cell-cell signaling	-0.001	0.003	-10000	0	-10000	0	0
MAP2K4	0.002	0.077	-10000	0	-0.7	4	4
YES1	-0.002	0.1	-10000	0	-0.94	4	4
Ephrin B1/EPHB1-2/NCK2	0.006	0.1	-10000	0	-0.31	23	23
PI3K	0.011	0.079	-10000	0	-0.7	4	4
mol:GDP	-0.013	0.13	-10000	0	-0.32	41	41
ITGA2B	-0.004	0.073	-10000	0	-0.24	31	31
endothelial cell proliferation	0.021	0.024	-10000	0	-0.13	1	1
FYN	-0.002	0.1	-10000	0	-0.94	4	4
MAP3K7	-0.005	0.081	-10000	0	-0.74	4	4
FGR	-0.019	0.12	-10000	0	-0.95	4	4
TIAM1	-0.015	0.13	-10000	0	-0.54	22	22
PIK3R1	0.019	0	-10000	0	-10000	0	0
RGS3	0.019	0	-10000	0	-10000	0	0
cell adhesion	-0.01	0.12	-10000	0	-0.49	10	10
LYN	-0.009	0.11	-10000	0	-0.94	4	4
Ephrin B1/EPHB1-2/Src Family Kinases	-0.013	0.093	-10000	0	-0.88	4	4
Ephrin B1/EPHB1-2	-0.019	0.085	-10000	0	-0.8	4	4
SRC	-0.002	0.099	-10000	0	-0.92	4	4
ITGB3	-0.033	0.14	-10000	0	-0.35	51	51
EPHB1	-0.006	0.094	-10000	0	-0.33	25	25
EPHB4	0.018	0.014	-10000	0	-0.24	1	1
RAC1	0.019	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.021	0.024	-10000	0	-0.13	1	1
alphaIIb/beta3 Integrin	-0.024	0.11	-10000	0	-0.36	26	26
BLK	-0.12	0.12	-10000	0	-0.76	6	6
HCK	-0.021	0.11	-10000	0	-0.96	4	4
regulation of stress fiber formation	-0.005	0.099	0.3	23	-10000	0	23
MAPK8	0.009	0.073	-10000	0	-0.66	4	4
Ephrin B1/EPHB1-2/RGS3	0.006	0.1	-10000	0	-0.3	24	24
endothelial cell migration	-0.002	0.073	-10000	0	-0.63	4	4
NCK2	0.019	0	-10000	0	-10000	0	0
PTPN13	0.018	0.077	-10000	0	-0.49	7	7
regulation of focal adhesion formation	-0.005	0.099	0.3	23	-10000	0	23
chemotaxis	-0.005	0.099	0.3	24	-10000	0	24
PIK3CA	0.018	0.014	-10000	0	-0.24	1	1
Rac1/GTP	-0.008	0.12	-10000	0	-0.29	41	41
angiogenesis	-0.019	0.085	-10000	0	-0.8	4	4
LCK	-0.068	0.14	-10000	0	-0.76	6	6

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

Figure S76. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S76. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.018	0.014	-10000	0	-0.24	1	1
NFATC1	0.056	0.055	-10000	0	-0.27	9	9
NFATC2	0.032	0.047	-10000	0	-0.25	2	2
NFATC3	0.027	0.03	-10000	0	-0.38	2	2
YWHAE	0.019	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.099	0.2	-10000	0	-0.44	81	81
Exportin 1/Ran/NUP214	0.039	0.001	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.1	0.22	-10000	0	-0.44	99	99
BCL2/BAX	0.028	0	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0.016	0.002	-10000	0	-10000	0	0
CaM/Ca2+	0.016	0.002	-10000	0	-10000	0	0
BAX	0.019	0	-10000	0	-10000	0	0
MAPK14	0.019	0.001	-10000	0	-10000	0	0
BAD	0.019	0	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.086	0.19	-10000	0	-0.42	81	81
Calcineurin A alpha-beta B1/BCL2	0.019	0	-10000	0	-10000	0	0
FKBP8	0.019	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.085	0.19	0.41	81	-10000	0	81
KPNB1	0.019	0	-10000	0	-10000	0	0
KPNA2	0.019	0	-10000	0	-10000	0	0
XPO1	0.019	0	-10000	0	-10000	0	0
SFN	-0.034	0.1	-10000	0	-0.24	73	73
MAP3K8	-0.003	0.11	-10000	0	-0.52	15	15
NFAT4/CK1 alpha	0.041	0.019	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	0.068	0.049	-10000	0	-0.24	1	1
CABIN1	-0.1	0.2	-10000	0	-0.45	81	81
CALM1	0.019	0.001	-10000	0	-10000	0	0
RAN	0.019	0	-10000	0	-10000	0	0
MAP3K1	0.019	0	-10000	0	-10000	0	0
CAMK4	-0.063	0.2	-10000	0	-0.54	54	54
mol:Ca2+	0.001	0.001	-10000	0	-10000	0	0
MAPK3	0.019	0	-10000	0	-10000	0	0
YWHAH	0.019	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.042	0.16	-10000	0	-0.38	63	63
YWHAB	0.019	0	-10000	0	-10000	0	0
MAPK8	0.019	0.001	-10000	0	-10000	0	0
MAPK9	0.019	0	-10000	0	-10000	0	0
YWHAG	0.019	0	-10000	0	-10000	0	0
FKBP1A	0.019	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.074	0.055	-10000	0	-0.27	2	2
PRKCH	0.016	0.041	-10000	0	-0.54	2	2
CABIN1/Cbp/p300	0.029	0.002	-10000	0	-10000	0	0
CASP3	0.019	0.001	-10000	0	-10000	0	0
PIM1	0.019	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.013	0.001	-10000	0	-10000	0	0
apoptosis	0	0.005	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.037	0.027	-10000	0	-10000	0	0
PRKCB	-0.15	0.26	-10000	0	-0.54	110	110
PRKCE	0.019	0	-10000	0	-10000	0	0
JNK2/NFAT4	0.035	0.028	-10000	0	-0.34	2	2
BAD/BCL-XL	0.028	0.009	-10000	0	-10000	0	0
PRKCD	0.019	0	-10000	0	-10000	0	0
NUP214	0.019	0	-10000	0	-10000	0	0
PRKCZ	0.016	0.041	-10000	0	-0.54	2	2
PRKCA	0.013	0.044	-10000	0	-0.28	7	7
PRKCG	0.01	0.025	-10000	0	-0.24	3	3
PRKCQ	-0.16	0.26	-10000	0	-0.54	116	116
FKBP38/BCL2	0.028	0	-10000	0	-10000	0	0
EP300	0.02	0.001	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.019	0	-10000	0	-10000	0	0
NFATc/JNK1	0.065	0.053	-10000	0	-0.27	1	1
CaM/Ca2+/FKBP38	0.027	0.002	-10000	0	-10000	0	0
FKBP12/FK506	0.014	0	-10000	0	-10000	0	0
CSNK1A1	0.024	0.002	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.025	0.12	-10000	0	-0.32	54	54
NFATc/ERK1	0.064	0.053	-10000	0	-0.27	1	1
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.1	0.22	-10000	0	-0.44	99	99
NR4A1	0.062	0.051	-10000	0	-0.49	1	1
GSK3B	0.019	0.001	-10000	0	-10000	0	0
positive T cell selection	0.027	0.03	-10000	0	-0.38	2	2
NFAT1/CK1 alpha	0.031	0.039	-10000	0	-0.22	2	2
RCH1/ KPNB1	0.028	0	-10000	0	-10000	0	0
YWHAQ	0.019	0	-10000	0	-10000	0	0
PRKACA	0.019	0.001	-10000	0	-10000	0	0
AKAP5	-0.077	0.21	-10000	0	-0.54	63	63
MEF2D	0.02	0.001	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.019	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.065	0.053	-10000	0	-0.27	1	1
CREBBP	0.02	0.001	-10000	0	-10000	0	0
BCL2	0.019	0	-10000	0	-10000	0	0

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.013	0	-9999	-10000	0	0
GNB1/GNG2	-0.024	0.076	-9999	-0.31	6	6
regulation of S phase of mitotic cell cycle	0	0.045	-9999	-10000	0	0
GNAO1	-0.094	0.13	-9999	-0.24	156	156
HRAS	0.019	0	-9999	-10000	0	0
SHBG/T-DHT	0.002	0.037	-9999	-0.13	26	26
PELP1	0.019	0	-9999	-10000	0	0
AKT1	0.013	0	-9999	-10000	0	0
MAP2K1	0.007	0.052	-9999	-10000	0	0
T-DHT/AR	-0.056	0.084	-9999	-0.16	143	143
G-protein coupled receptor activity	0	0	-9999	-10000	0	0
mol:GTP	0	0.001	-9999	-0.004	11	11
GNAI2	0.019	0	-9999	-10000	0	0
GNAI3	0.019	0	-9999	-10000	0	0
GNAI1	0.005	0.058	-9999	-0.24	19	19
mol:GDP	-0.039	0.048	-9999	-10000	0	0
cell proliferation	0.023	0.055	-9999	-10000	0	0
PIK3CA	0.018	0.014	-9999	-0.24	1	1
FOS	0.031	0.053	-9999	-10000	0	0
mol:Ca2+	-0.01	0.019	-9999	-0.051	19	19
MAPK3	0.016	0.052	-9999	-10000	0	0
MAPK1	0.019	0.03	-9999	-10000	0	0
PIK3R1	0.019	0	-9999	-10000	0	0
mol:IP3	0	0	-9999	-0.002	11	11
cAMP biosynthetic process	0.008	0.038	-9999	-0.12	24	24
GNG2	0.01	0.071	-9999	-0.54	6	6
potassium channel inhibitor activity	0	0	-9999	-0.002	11	11
HRAS/GTP	-0.008	0.058	-9999	-10000	0	0
actin cytoskeleton reorganization	0.029	0.006	-9999	-10000	0	0
SRC	0.019	0	-9999	-10000	0	0
voltage-gated calcium channel activity	0	0	-9999	-0.002	11	11
PI3K	0.025	0.008	-9999	-10000	0	0
apoptosis	-0.028	0.044	-9999	-10000	0	0
T-DHT/AR/PELP1	-0.033	0.072	-9999	-0.13	3	3
HRAS/GDP	-0.012	0.059	-9999	-10000	0	0
CREB1	0.029	0.045	-9999	-10000	0	0
RAC1-CDC42/GTP	0.037	0.006	-9999	-10000	0	0
AR	-0.085	0.13	-9999	-0.24	143	143
GNB1	0.019	0	-9999	-10000	0	0
RAF1	-0.001	0.055	-9999	-10000	0	0
RAC1-CDC42/GDP	-0.002	0.059	-9999	-10000	0	0
T-DHT/AR/PELP1/Src	-0.018	0.067	-9999	-10000	0	0
MAP2K2	0.007	0.052	-9999	-10000	0	0
T-DHT/AR/PELP1/Src/PI3K	0	0.045	-9999	-10000	0	0
GNAZ	-0.016	0.094	-9999	-0.26	46	46
SHBG	0	0.067	-9999	-0.24	26	26
Gi family/GNB1/GNG2/GDP	-0.018	0.075	-9999	-0.3	7	7
mol:T-DHT	0	0	-9999	-10000	0	0
RAC1	0.019	0	-9999	-10000	0	0
GNRH1	0.005	0.055	-9999	-0.39	7	7
Gi family/GTP	-0.038	0.065	-9999	-0.19	18	18
CDC42	0.019	0	-9999	-10000	0	0

×

Neurotrophic factor-mediated Trk receptor signaling

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
CRKL	0.018	0.014	-10000	0	-0.24	1	1
RAS family/GTP/Tiam1	0.004	0.08	-10000	0	-0.24	22	22
NT3 (dimer)/TRKC	-0.019	0.12	-10000	0	-0.39	28	28
NT3 (dimer)/TRKB	-0.023	0.1	-10000	0	-0.29	29	29
SHC/Grb2/SOS1/GAB1/PI3K	0.044	0.005	-10000	0	-10000	0	0
RAPGEF1	0.019	0	-10000	0	-10000	0	0
BDNF	-0.12	0.24	-10000	0	-0.54	88	88
PIK3CA	0.018	0.014	-10000	0	-0.24	1	1
DYNLT1	0.019	0	-10000	0	-10000	0	0
NTRK1	-0.001	0.1	-10000	0	-0.5	14	14
NTRK2	-0.019	0.1	-10000	0	-0.28	47	47
NTRK3	-0.025	0.14	-10000	0	-0.49	31	31
NT-4/5 (dimer)/TRKB	-0.022	0.089	-10000	0	-0.29	21	21
neuron apoptosis	0.078	0.12	0.29	44	-10000	0	44
SHC 2-3/Grb2	-0.083	0.12	-10000	0	-0.32	44	44
SHC1	0.019	0	-10000	0	-10000	0	0
SHC2	-0.073	0.12	-10000	0	-0.3	40	40
SHC3	-0.062	0.11	-10000	0	-0.32	22	22
STAT3 (dimer)	0.024	0.03	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	-0.014	0.1	-10000	0	-0.33	23	23
RIN/GDP	0.015	0.053	-10000	0	-10000	0	0
GIPC1	0.019	0	-10000	0	-10000	0	0
KRAS	0.018	0.014	-10000	0	-0.24	1	1
DNAJA3	-0.003	0.071	-10000	0	-0.26	15	15
RIN/GTP	0	0	-10000	0	-10000	0	0
CCND1	0.026	0.052	-10000	0	-10000	0	0
MAGED1	0.019	0	-10000	0	-10000	0	0
PTPN11	0.019	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.038	0	-10000	0	-10000	0	0
GRB2	0.019	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.026	0.14	-10000	0	-0.36	51	51
TRKA/NEDD4-2	0.01	0.084	-10000	0	-0.39	15	15
ELMO1	-0.007	0.12	-10000	0	-0.54	17	17
RhoG/GTP/ELMO1/DOCK1	0.009	0.074	-10000	0	-0.32	17	17
NGF	0.002	0.062	-10000	0	-0.24	22	22
HRAS	0.019	0	-10000	0	-10000	0	0
DOCK1	0.019	0	-10000	0	-10000	0	0
GAB2	0.015	0.03	-10000	0	-0.24	5	5
RIT2	0	0	-10000	0	-10000	0	0
RIT1	0.019	0	-10000	0	-10000	0	0
FRS2	0.017	0.024	-10000	0	-0.24	3	3
DNM1	-0.008	0.08	-10000	0	-0.24	38	38
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.019	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.013	0.089	-10000	0	-0.26	32	32
mol:GDP	0.019	0.072	-10000	0	-0.26	1	1
NGF (dimer)	0.002	0.062	-10000	0	-0.24	22	22
RhoG/GDP	-0.005	0.085	-10000	0	-0.39	17	17
RIT1/GDP	0.023	0.055	-10000	0	-10000	0	0
TIAM1	-0.015	0.13	-10000	0	-0.54	22	22
PIK3R1	0.019	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.069	0.16	-10000	0	-0.32	92	92
KIDINS220/CRKL/C3G	0.028	0.009	-10000	0	-10000	0	0
SHC/RasGAP	0.027	0.021	-10000	0	-0.38	1	1
FRS2 family/SHP2	0.037	0.014	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0.049	0	-10000	0	-10000	0	0
RIT1/GTP	0.014	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.004	0.068	-10000	0	-0.24	27	27
RAP1/GDP	-0.008	0.028	-10000	0	-10000	0	0
KIDINS220/CRKL	0.018	0.014	-10000	0	-0.24	1	1
BDNF (dimer)	-0.12	0.24	-10000	0	-0.54	88	88
ubiquitin-dependent protein catabolic process	0.013	0.079	-10000	0	-0.32	15	15
Schwann cell development	-0.023	0.026	-10000	0	-10000	0	0
EHD4	0.019	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.048	0.013	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.045	0.013	-10000	0	-10000	0	0
RAP1B	0.019	0	-10000	0	-10000	0	0
RAP1A	0.019	0	-10000	0	-10000	0	0
CDC42/GTP	-0.096	0.15	-10000	0	-0.33	70	70
ABL1	0.019	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.028	0	-10000	0	-10000	0	0
Rap1/GTP	0.014	0.07	-10000	0	-10000	0	0
STAT3	0.024	0.03	-10000	0	-10000	0	0
axon guidance	-0.11	0.13	-10000	0	-0.32	70	70
MAPK3	-0.02	0.13	-10000	0	-0.32	51	51
MAPK1	-0.02	0.13	-10000	0	-0.32	51	51
CDC42/GDP	0.023	0.055	-10000	0	-10000	0	0
NTF3	-0.004	0.068	-10000	0	-0.24	27	27
NTF4	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/FAIM	0.013	0.078	-10000	0	-0.32	15	15
PI3K	0.028	0.009	-10000	0	-10000	0	0
FRS3	0.019	0	-10000	0	-10000	0	0
FAIM	0.014	0.05	-10000	0	-0.54	3	3
GAB1	0.019	0	-10000	0	-10000	0	0
RASGRF1	-0.029	0.11	-10000	0	-0.28	42	42
SOS1	0.019	0	-10000	0	-10000	0	0
MCF2L	-0.056	0.11	-10000	0	-0.32	35	35
RGS19	0.019	0	-10000	0	-10000	0	0
CDC42	0.019	0	-10000	0	-10000	0	0
RAS family/GTP	0.046	0.046	-10000	0	-10000	0	0
Rac1/GDP	0.023	0.055	-10000	0	-10000	0	0
NGF (dimer)/TRKA/GRIT	0.004	0.071	-10000	0	-0.32	12	12
neuron projection morphogenesis	0.014	0.069	-10000	0	-0.5	1	1
NGF (dimer)/TRKA/NEDD4-2	0.013	0.079	-10000	0	-0.32	15	15
MAP2K1	0.042	0	-10000	0	-10000	0	0
NGFR	-0.027	0.11	-10000	0	-0.26	59	59
NGF (dimer)/TRKA/GIPC/GAIP	0.019	0.06	-10000	0	-0.23	12	12
RAS family/GTP/PI3K	0.036	0.007	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	0.055	0.012	-10000	0	-10000	0	0
NRAS	0.019	0	-10000	0	-10000	0	0
GRB2/SOS1	0.028	0	-10000	0	-10000	0	0
PRKCI	0.019	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.019	0	-10000	0	-10000	0	0
PRKCZ	0.016	0.041	-10000	0	-0.54	2	2
MAPKKK cascade	-0.031	0.12	-10000	0	-0.56	15	15
RASA1	0.017	0.029	-10000	0	-0.54	1	1
TRKA/c-Abl	0.013	0.074	-10000	0	-0.38	12	12
SQSTM1	0.019	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.051	0.14	-10000	0	-0.29	92	92
NGF (dimer)/TRKA/p62/Atypical PKCs	0.035	0.067	-10000	0	-0.26	14	14
MATK	-0.049	0.18	-10000	0	-0.53	45	45
NEDD4L	0.014	0.05	-10000	0	-0.54	3	3
RAS family/GDP	-0.01	0.025	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.011	0.075	-10000	0	-0.28	15	15
Rac1/GTP	-0.04	0.074	-10000	0	-0.25	24	24
FRS2 family/SHP2/CRK family	0.055	0.014	-10000	0	-10000	0	0

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.016	0.036	-9999	-0.32	4	4
ADCY5	-0.056	0.14	-9999	-0.32	80	80
ADCY6	0.019	0.013	-9999	-10000	0	0
ADCY7	0.018	0.025	-9999	-0.32	2	2
ADCY1	-0.035	0.13	-9999	-0.32	58	58
ADCY2	-0.045	0.071	-9999	-10000	0	0
ADCY3	0.02	0	-9999	-10000	0	0
ADCY8	0.001	0.042	-9999	-10000	0	0
PRKCE	0.013	0	-9999	-10000	0	0
ADCY9	0.02	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.029	0.057	-9999	-0.19	11	11

×

Reelin signaling pathway

Figure S80. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S80. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.027	0.021	-9999	-0.38	1	1
VLDLR	0.005	0.086	-9999	-0.54	9	9
CRKL	0.018	0.014	-9999	-0.24	1	1
LRPAP1	0.019	0	-9999	-10000	0	0
FYN	0.019	0	-9999	-10000	0	0
ITGA3	0.002	0.068	-9999	-0.26	23	23
RELN/VLDLR/Fyn	-0.009	0.084	-9999	-0.34	9	9
MAPK8IP1/MKK7/MAP3K11/JNK1	0.052	0.026	-9999	-0.26	1	1
AKT1	-0.002	0.068	-9999	-0.26	10	10
MAP2K7	0.019	0	-9999	-10000	0	0
RAPGEF1	0.019	0	-9999	-10000	0	0
DAB1	-0.027	0.087	-9999	-0.24	51	51
RELN/LRP8/DAB1	-0.022	0.079	-9999	-0.22	27	27
LRPAP1/LRP8	0.028	0	-9999	-10000	0	0
RELN/LRP8/DAB1/Fyn	-0.011	0.076	-9999	-0.2	27	27
DAB1/alpha3/beta1 Integrin	-0.039	0.067	-9999	-0.34	6	6
long-term memory	-0.023	0.098	-9999	-0.31	17	17
DAB1/LIS1	-0.004	0.085	-9999	-0.3	9	9
DAB1/CRLK/C3G	-0.033	0.062	-9999	-0.4	3	3
PIK3CA	0.018	0.014	-9999	-0.24	1	1
DAB1/NCK2	-0.003	0.086	-9999	-0.3	9	9
ARHGEF2	0.017	0.029	-9999	-0.54	1	1
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.003	0.071	-9999	-0.24	29	29
CDK5R1	0.017	0.029	-9999	-0.54	1	1
RELN	-0.047	0.11	-9999	-0.24	91	91
PIK3R1	0.019	0	-9999	-10000	0	0
RELN/LRP8/Fyn	0	0.066	-9999	-10000	0	0
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.011	0.088	-9999	-0.3	7	7
MAPK8	0.019	0.001	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.03	0.094	-9999	-0.26	34	34
ITGB1	0.017	0.019	-9999	-0.24	2	2
MAP1B	-0.018	0.087	-9999	-0.31	12	12
RELN/LRP8	0	0.066	-9999	-10000	0	0
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.022	0.094	-9999	-0.3	12	12
PI3K	0.028	0.009	-9999	-10000	0	0
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	0.015	0.05	-9999	-0.34	2	2
RAP1A	0.006	0.077	-9999	-0.37	3	3
PAFAH1B1	0.019	0	-9999	-10000	0	0
MAPK8IP1	0.013	0.038	-9999	-0.24	8	8
CRLK/C3G	0.028	0.009	-9999	-10000	0	0
GRIN2B	-0.025	0.087	-9999	-0.24	50	50
NCK2	0.019	0	-9999	-10000	0	0
neuron differentiation	0.02	0.045	-9999	-10000	0	0
neuron adhesion	0.011	0.08	-9999	-0.33	4	4
LRP8	0.019	0	-9999	-10000	0	0
GSK3B	0.005	0.065	-9999	-0.35	3	3
RELN/VLDLR/DAB1/Fyn	-0.018	0.09	-9999	-0.23	34	34
MAP3K11	0.019	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.01	0.072	-9999	-0.29	10	10
CDK5	0.019	0	-9999	-10000	0	0
MAPT	-0.1	0.12	-9999	-0.22	185	185
neuron migration	0.021	0.076	-9999	-0.35	3	3
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	0.02	0.045	-9999	-10000	0	0
RELN/VLDLR	0.005	0.079	-9999	-0.3	9	9

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.014	0	-10000	0	-10000	0	0
PRKCZ	0.016	0.041	-10000	0	-0.54	2	2
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.019	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	0.002	0.08	-10000	0	-0.32	9	9
IRAK/TOLLIP	0.032	0	-10000	0	-10000	0	0
IKBKB	0.019	0	-10000	0	-10000	0	0
IKBKG	0.019	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.042	0.15	-10000	0	-0.39	53	53
IL1A	0.004	0.053	-10000	0	-0.24	16	16
IL1B	-0.037	0.16	-10000	0	-0.42	48	48
IRAK/TRAF6/p62/Atypical PKCs	0.055	0.021	-10000	0	-10000	0	0
IL1R2	-0.062	0.2	-10000	0	-0.54	53	53
IL1R1	0.016	0.041	-10000	0	-0.54	2	2
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.014	0.075	0.21	4	-0.28	9	13
TOLLIP	0.019	0	-10000	0	-10000	0	0
TICAM2	0.009	0.071	-10000	0	-0.54	6	6
MAP3K3	0.019	0	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.013	0	-10000	0	-10000	0	0
IKK complex/ELKS	0.07	0.007	-10000	0	-10000	0	0
JUN	0.026	0.047	-10000	0	-0.22	7	7
MAP3K7	0.019	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.003	0.12	-10000	0	-0.28	49	49
IL1 alpha/IL1R1/IL1RAP/MYD88	0.028	0.055	-10000	0	-0.25	6	6
PIK3R1	0.019	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.037	0.053	-10000	0	-0.26	3	3
IL1 beta fragment/IL1R1/IL1RAP	-0.018	0.13	-10000	0	-0.32	50	50
NFKB1	0.019	0	-10000	0	-10000	0	0
MAPK8	0.032	0.036	-10000	0	-0.23	7	7
IRAK1	0.022	0	-10000	0	-10000	0	0
IL1RN/IL1R1	0.013	0.073	-10000	0	-0.38	11	11
IRAK4	0.019	0	-10000	0	-10000	0	0
PRKCI	0.019	0	-10000	0	-10000	0	0
TRAF6	0.019	0	-10000	0	-10000	0	0
PI3K	0.028	0.009	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.008	0.089	-10000	0	-0.34	10	10
CHUK	0.019	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.018	0.13	-10000	0	-0.32	50	50
IL1 beta/IL1R2	-0.069	0.19	-10000	0	-0.39	86	86
IRAK/TRAF6/TAK1/TAB1/TAB2	0.036	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.038	0.092	-10000	0	-0.45	8	8
IRAK3	0.011	0.064	-10000	0	-0.54	5	5
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.002	0.13	-10000	0	-0.29	52	52
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.03	0.04	-10000	0	-0.23	3	3
IL1 alpha/IL1R1/IL1RAP	0.017	0.057	-10000	0	-0.28	5	5
RELA	0.019	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.019	0	-10000	0	-10000	0	0
MYD88	0.017	0.029	-10000	0	-0.54	1	1
IRAK/TRAF6/MEKK3	0.043	0	-10000	0	-10000	0	0
IL1RAP	0.001	0.066	-10000	0	-0.24	25	25
UBE2N	0.019	0	-10000	0	-10000	0	0
IRAK/TRAF6	-0.038	0.092	-10000	0	-0.44	10	10
CASP1	-0.012	0.13	-10000	0	-0.54	20	20
IL1RN/IL1R2	-0.044	0.16	-10000	0	-0.39	60	60
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.006	0.13	-10000	0	-0.3	49	49
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.037	0.04	-10000	0	-0.3	3	3
PIK3CA	0.018	0.014	-10000	0	-0.24	1	1
IL1RN	0.002	0.091	-10000	0	-0.43	14	14
TRAF6/TAK1/TAB1/TAB2	0.028	0	-10000	0	-10000	0	0
MAP2K6	0.027	0.038	-10000	0	-0.24	7	7

×

Syndecan-3-mediated signaling 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
CTTN	0.017	0.024	-9999	-0.24	3	3
Syndecan-3/Src/Cortactin	0.021	0.051	-9999	-10000	0	0
Syndecan-3/Neurocan	0.017	0.028	-9999	-10000	0	0
POMC	-0.047	0.18	-9999	-0.52	45	45
EGFR	-0.007	0.086	-9999	-0.27	32	32
Syndecan-3/EGFR	0.02	0.041	-9999	-0.26	3	3
AGRP	0.003	0.044	-9999	-0.24	11	11
NCSTN	0.019	0	-9999	-10000	0	0
PSENEN	0.019	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.014	0.05	-9999	-0.54	3	3
APH1A	0.019	0	-9999	-10000	0	0
NCAN	0.001	0.055	-9999	-0.24	17	17
long-term memory	0.04	0.014	-9999	-10000	0	0
Syndecan-3/IL8	0	0.057	-9999	-0.28	3	3
PSEN1	0.019	0	-9999	-10000	0	0
Src/Cortactin	0.027	0.016	-9999	-10000	0	0
FYN	0.019	0	-9999	-10000	0	0
limb bud formation	-0.001	0.008	-9999	-10000	0	0
MC4R	-0.031	0.095	-9999	-0.24	60	60
SRC	0.019	0	-9999	-10000	0	0
PTN	-0.046	0.11	-9999	-0.24	90	90
FGFR/FGF/Syndecan-3	-0.001	0.008	-9999	-10000	0	0
neuron projection morphogenesis	0.015	0.051	-9999	-10000	0	0
Syndecan-3/AgRP	0.014	0.027	-9999	-0.21	1	1
Syndecan-3/AgRP/MC4R	0.008	0.047	-9999	-10000	0	0
Fyn/Cortactin	0.027	0.016	-9999	-10000	0	0
SDC3	-0.001	0.008	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	0	0.057	-9999	-0.28	3	3
IL8	-0.05	0.12	-9999	-0.25	93	93
Syndecan-3/Fyn/Cortactin	0.041	0.014	-9999	-10000	0	0
Syndecan-3/CASK	-0.001	0.007	-9999	-10000	0	0
alpha-MSH/MC4R	-0.054	0.14	-9999	-0.4	43	43
Gamma Secretase	0.054	0.028	-9999	-0.26	3	3

×

Glypican 2 network

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
MDK	0.004	0.07	-9999	-0.3	17	17
GPC2	0.008	0.073	-9999	-0.46	8	8
GPC2/Midkine	0.01	0.074	-9999	-0.37	11	11
neuron projection morphogenesis	0.01	0.074	-9999	-0.37	11	11

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.015	0.03	-9999	-0.24	5	5
mol:S1P	0.002	0	-9999	-10000	0	0
S1P1/S1P/Gi	-0.011	0.06	-9999	-0.24	4	4
GNAO1	-0.092	0.13	-9999	-0.24	156	156
S1P/S1P3/G12/G13	0.037	0.03	-9999	-0.29	3	3
AKT1	0.019	0.03	-9999	-10000	0	0
AKT3	0.026	0.043	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.015	0.03	-9999	-0.24	5	5
GNAI2	0.021	0	-9999	-10000	0	0
GNAI3	0.021	0	-9999	-10000	0	0
GNAI1	0.007	0.058	-9999	-0.24	19	19
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.016	0.052	-9999	-0.46	4	4
S1PR2	0.019	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	-0.004	0.067	-9999	-0.27	5	5
MAPK3	0.003	0.063	-9999	-0.29	3	3
MAPK1	0.003	0.063	-9999	-0.29	3	3
JAK2	-0.006	0.09	-9999	-0.35	12	12
CXCR4	-0.018	0.11	-9999	-0.33	29	29
FLT1	0.022	0.014	-9999	-0.24	1	1
RhoA/GDP	0.014	0	-9999	-10000	0	0
Rac1/GDP	0.014	0	-9999	-10000	0	0
SRC	0.003	0.063	-9999	-0.29	3	3
S1P/S1P3/Gi	-0.004	0.067	-9999	-0.27	5	5
RAC1	0.019	0	-9999	-10000	0	0
RhoA/GTP	0.005	0.062	-9999	-0.28	3	3
VEGFA	0.007	0.061	-9999	-0.24	21	21
S1P/S1P2/Gi	-0.006	0.061	-9999	-0.22	4	4
VEGFR1 homodimer/VEGFA homodimer	0.027	0.045	-9999	-0.3	1	1
RHOA	0.019	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.023	0.13	-9999	-0.26	73	73
GNAQ	0.019	0	-9999	-10000	0	0
GNAZ	-0.014	0.094	-9999	-0.26	46	46
G12/G13	0.028	0	-9999	-10000	0	0
GNA14	-0.084	0.22	-9999	-0.53	69	69
GNA15	0.002	0.095	-9999	-0.54	11	11
GNA12	0.019	0	-9999	-10000	0	0
GNA13	0.019	0	-9999	-10000	0	0
GNA11	0.019	0	-9999	-10000	0	0
Rac1/GTP	0.005	0.062	-9999	-0.28	3	3

×

ErbB2/ErbB3 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.021	0.003	-9999	-10000	0	0
RAS family/GTP	0.034	0.076	-9999	-0.29	10	10
NFATC4	0.018	0.067	-9999	-0.26	9	9
ERBB2IP	0.018	0.002	-9999	-10000	0	0
HSP90 (dimer)	0.017	0.029	-9999	-0.54	1	1
mammary gland morphogenesis	0.021	0.069	-9999	-0.26	17	17
JUN	0.042	0.074	-9999	-0.21	6	6
HRAS	0.019	0.001	-9999	-10000	0	0
DOCK7	0.026	0.066	-9999	-0.25	17	17
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.016	0.075	-9999	-0.3	17	17
AKT1	0.013	0.002	-9999	-10000	0	0
BAD	0.021	0.001	-9999	-10000	0	0
MAPK10	0.017	0.05	-9999	-0.18	8	8
mol:GTP	-0.001	0.002	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	0.023	0.074	-9999	-0.28	17	17
RAF1	0.036	0.085	-9999	-0.31	9	9
ErbB2/ErbB3/neuregulin 2	0.01	0.072	-9999	-0.32	16	16
STAT3	0.028	0.005	-9999	-10000	0	0
cell migration	0.032	0.045	-9999	-0.16	7	7
mol:PI-3-4-5-P3	0	0.001	-9999	-10000	0	0
cell proliferation	-0.006	0.25	-9999	-0.58	52	52
FOS	0.025	0.16	-9999	-0.33	52	52
NRAS	0.019	0.001	-9999	-10000	0	0
mol:Ca2+	0.021	0.069	-9999	-0.26	17	17
MAPK3	0.006	0.2	-9999	-0.45	52	52
MAPK1	0.006	0.2	-9999	-0.45	52	52
JAK2	0.022	0.072	-9999	-0.25	18	18
NF2	0.007	0.011	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0.015	0.07	-9999	-0.29	17	17
NRG1	-0.001	0.074	-9999	-0.29	20	20
GRB2/SOS1	0.028	0.001	-9999	-10000	0	0
MAPK8	0.032	0.069	-9999	-0.26	17	17
MAPK9	0.033	0.038	-9999	-0.16	4	4
ERBB2	-0.001	0.002	-9999	-10000	0	0
ERBB3	-0.002	0.11	-9999	-0.54	14	14
SHC1	0.019	0.001	-9999	-10000	0	0
RAC1	0.019	0	-9999	-10000	0	0
apoptosis	-0.019	0.009	-9999	-10000	0	0
STAT3 (dimer)	0.028	0.005	-9999	-10000	0	0
RNF41	0.026	0.004	-9999	-10000	0	0
FRAP1	0.01	0.001	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.009	0.038	-9999	-0.23	4	4
ErbB2/ErbB2/HSP90 (dimer)	0.013	0.018	-9999	-0.33	1	1
CHRNA1	-0.023	0.26	-9999	-0.64	52	52
myelination	0.018	0.064	-9999	-0.25	9	9
PPP3CB	0.025	0.062	-9999	-0.23	17	17
KRAS	0.018	0.014	-9999	-0.24	1	1
RAC1-CDC42/GDP	0.034	0.064	-9999	-0.24	17	17
NRG2	0.011	0.057	-9999	-0.37	7	7
mol:GDP	0.015	0.07	-9999	-0.29	17	17
SOS1	0.019	0.001	-9999	-10000	0	0
MAP2K2	0.035	0.097	-9999	-0.34	8	8
SRC	0.019	0	-9999	-10000	0	0
mol:cAMP	0	0.001	-9999	-10000	0	0
PTPN11	0.029	0.065	-9999	-0.25	17	17
MAP2K1	0.013	0.17	-9999	-0.35	53	53
heart morphogenesis	0.021	0.069	-9999	-0.26	17	17
RAS family/GDP	0.04	0.069	-9999	-0.28	9	9
GRB2	0.019	0.001	-9999	-10000	0	0
PRKACA	0	0.004	-9999	-10000	0	0
CHRNE	0.018	0.031	-9999	-0.1	17	17
HSP90AA1	0.017	0.029	-9999	-0.54	1	1
activation of caspase activity	-0.013	0.002	-9999	-10000	0	0
nervous system development	0.021	0.069	-9999	-0.26	17	17
CDC42	0.019	0	-9999	-10000	0	0

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0.038	0.027	-10000	0	-10000	0	0
HDAC1	0.013	0.029	-10000	0	-0.54	1	1
AES	0.018	0.001	-10000	0	-10000	0	0
FBXW11	0.019	0	-10000	0	-10000	0	0
DTX1	-0.11	0.23	-10000	0	-0.54	85	85
LRP6/FZD1	0.025	0.023	-10000	0	-10000	0	0
TLE1	0.016	0.029	-10000	0	-0.54	1	1
AP1	0.009	0.055	-10000	0	-0.27	8	8
NCSTN	0.019	0	-10000	0	-10000	0	0
ADAM10	0.019	0	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.052	0.025	-10000	0	-10000	0	0
NICD/RBPSUH	0.043	0.007	-10000	0	-10000	0	0
WIF1	-0.024	0.086	-10000	0	-0.24	48	48
NOTCH1	0.034	0.007	-10000	0	-10000	0	0
PSENEN	0.019	0	-10000	0	-10000	0	0
KREMEN2	-0.056	0.19	-10000	0	-0.54	49	49
DKK1	-0.078	0.2	-10000	0	-0.44	78	78
beta catenin/beta TrCP1	0.04	0.03	0.24	1	-10000	0	1
APH1B	0.014	0.05	-10000	0	-0.54	3	3
APH1A	0.019	0	-10000	0	-10000	0	0
AXIN1	0.008	0.016	0.26	1	-10000	0	1
CtBP/CBP/TCF1/TLE1/AES	0.027	0.024	-10000	0	-0.25	2	2
PSEN1	0.019	0	-10000	0	-10000	0	0
FOS	0.011	0.045	-10000	0	-0.24	11	11
JUN	-0.007	0.078	-10000	0	-0.24	36	36
MAP3K7	0.017	0.002	-10000	0	-10000	0	0
CTNNB1	0.029	0.033	0.21	6	-10000	0	6
MAPK3	0.019	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.019	0.13	-10000	0	-0.33	51	51
HNF1A	0.018	0.001	-10000	0	-10000	0	0
CTBP1	0.018	0.001	-10000	0	-10000	0	0
MYC	0.026	0.027	-10000	0	-10000	0	0
NKD1	-0.005	0.093	-10000	0	-0.33	25	25
FZD1	0.015	0.033	-10000	0	-0.24	6	6
NOTCH1 precursor/Deltex homolog 1	-0.024	0.12	-10000	0	-0.31	1	1
apoptosis	0.01	0.055	-10000	0	-0.27	8	8
Delta 1/NOTCHprecursor	0.04	0.028	-10000	0	-10000	0	0
DLL1	0.014	0.052	-10000	0	-0.46	4	4
PPARD	0.026	0.024	-10000	0	-10000	0	0
Gamma Secretase	0.055	0.028	-10000	0	-0.26	3	3
APC	0.008	0.016	0.26	1	-10000	0	1
DVL1	0.029	0.023	-10000	0	-10000	0	0
CSNK2A1	0.019	0.001	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.068	0.17	-10000	0	-0.35	91	91
LRP6	0.019	0	-10000	0	-10000	0	0
CSNK1A1	0.019	0.001	-10000	0	-10000	0	0
NLK	0.016	0.004	-10000	0	-10000	0	0
CCND1	0.019	0.055	-10000	0	-10000	0	0
WNT1	-0.031	0.15	-10000	0	-0.52	32	32
Axin1/APC/beta catenin	0.05	0.025	0.3	1	-10000	0	1
DKK2	0.001	0.075	-10000	0	-0.28	21	21
NOTCH1 precursor/DVL1	0.053	0.018	-10000	0	-10000	0	0
GSK3B	0.018	0	-10000	0	-10000	0	0
FRAT1	0.016	0.029	-10000	0	-0.54	1	1
NOTCH/Deltex homolog 1	-0.026	0.12	-10000	0	-0.31	1	1
PPP2R5D	0.027	0.047	0.29	7	-10000	0	7
MAPK1	0.019	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.006	0.1	-10000	0	-0.29	34	34
RBPJ	0.019	0	-10000	0	-10000	0	0
CREBBP	0.022	0.005	-10000	0	-10000	0	0

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.014	0.05	-9999	-0.31	1	1
PDGFRB	0.015	0.031	-9999	-0.24	5	5
SPHK1	-0.008	0.078	-9999	-0.83	3	3
mol:S1P	0.008	0.075	-9999	-0.63	4	4
S1P1/S1P/Gi	-0.018	0.095	-9999	-0.36	9	9
GNAO1	-0.094	0.13	-9999	-0.24	156	156
PDGFB-D/PDGFRB/PLCgamma1	-0.006	0.089	-9999	-0.4	5	5
PLCG1	-0.012	0.091	-9999	-0.39	6	6
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.015	0.031	-9999	-0.24	5	5
GNAI2	0.018	0.004	-9999	-10000	0	0
GNAI3	0.018	0.003	-9999	-10000	0	0
GNAI1	0.005	0.059	-9999	-0.25	19	19
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.008	0.041	-9999	-0.27	1	1
S1P1/S1P	0.015	0.071	-9999	-0.42	5	5
negative regulation of cAMP metabolic process	-0.018	0.093	-9999	-0.34	10	10
MAPK3	-0.016	0.11	-9999	-0.43	9	9
calcium-dependent phospholipase C activity	-0.001	0.002	-9999	-10000	0	0
Rac1/GDP	0.014	0	-9999	-10000	0	0
RhoA/GDP	0.014	0	-9999	-10000	0	0
KDR	0.014	0.036	-9999	-0.24	7	7
PLCB2	0.014	0.083	-9999	-0.37	9	9
RAC1	0.019	0	-9999	-10000	0	0
RhoA/GTP	-0.013	0.049	-9999	-0.35	5	5
receptor internalization	0.014	0.066	-9999	-0.39	5	5
PTGS2	-0.024	0.15	-9999	-0.93	4	4
Rac1/GTP	-0.013	0.049	-9999	-0.35	5	5
RHOA	0.019	0	-9999	-10000	0	0
VEGFA	0.004	0.062	-9999	-0.25	21	21
negative regulation of T cell proliferation	-0.018	0.093	-9999	-0.34	10	10
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.016	0.094	-9999	-0.26	46	46
MAPK1	-0.016	0.11	-9999	-0.45	8	8
S1P1/S1P/PDGFB-D/PDGFRB	0.021	0.074	-9999	-0.4	5	5
ABCC1	0.017	0.029	-9999	-0.54	1	1

×

Canonical Wnt signaling 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.012	0.03	-10000	0	-0.54	1	1
AES	0.015	0.007	-10000	0	-10000	0	0
FBXW11	0.019	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
LRP6/FZD1	0.025	0.023	-10000	0	-10000	0	0
SMAD4	0.019	0	-10000	0	-10000	0	0
DKK2	0.001	0.075	-10000	0	-0.28	21	21
TLE1	0.013	0.03	-10000	0	-0.54	1	1
MACF1	0.019	0	-10000	0	-10000	0	0
CTNNB1	0.018	0.074	-10000	0	-0.28	3	3
WIF1	-0.024	0.086	-10000	0	-0.24	48	48
beta catenin/RanBP3	-0.012	0.067	0.31	4	-10000	0	4
KREMEN2	-0.056	0.19	-10000	0	-0.54	49	49
DKK1	-0.078	0.2	-10000	0	-0.44	78	78
beta catenin/beta TrCP1	0.028	0.071	-10000	0	-0.26	1	1
FZD1	0.015	0.033	-10000	0	-0.24	6	6
AXIN2	0.012	0.09	-10000	0	-1.5	1	1
AXIN1	0.019	0.001	-10000	0	-10000	0	0
RAN	0.019	0	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.038	0.017	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.057	0.057	-10000	0	-0.4	1	1
Axin1/APC/GSK3	0.038	0.04	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin/Macf1	0.032	0.084	-10000	0	-0.27	1	1
HNF1A	0.014	0.007	-10000	0	-10000	0	0
CTBP1	0.014	0.007	-10000	0	-10000	0	0
MYC	0.017	0.037	-10000	0	-10000	0	0
RANBP3	0.019	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.019	0.13	-10000	0	-0.33	51	51
NKD1	-0.005	0.093	-10000	0	-0.33	25	25
TCF4	0.007	0.057	-10000	0	-0.37	7	7
TCF3	0.014	0.007	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0.017	0.091	-10000	0	-0.28	30	30
Ran/GTP	0.014	0.001	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.008	0.066	0.36	4	-10000	0	4
LEF1	-0.004	0.099	-10000	0	-0.54	12	12
DVL1	0.033	0.025	-10000	0	-10000	0	0
CSNK2A1	0.019	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.071	0.059	-10000	0	-0.38	1	1
DKK1/LRP6/Kremen 2	-0.068	0.17	-10000	0	-0.35	91	91
LRP6	0.019	0	-10000	0	-10000	0	0
CSNK1A1	0.014	0.008	-10000	0	-10000	0	0
NLK	0.02	0.002	-10000	0	-10000	0	0
CCND1	0.011	0.06	-10000	0	-10000	0	0
WNT1	-0.03	0.15	-10000	0	-0.52	32	32
GSK3A	0.019	0.001	-10000	0	-10000	0	0
GSK3B	0.019	0	-10000	0	-10000	0	0
FRAT1	0.017	0.029	-10000	0	-0.54	1	1
PPP2R5D	0.029	0.047	0.28	7	-10000	0	7
APC	0.015	0.082	-10000	0	-0.25	30	30
WNT1/LRP6/FZD1	0.025	0.071	-10000	0	-0.2	13	13
CREBBP	0.014	0.007	-10000	0	-10000	0	0

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.02	0.058	-10000	0	-10000	0	0
epithelial cell differentiation	-0.023	0.042	-10000	0	-10000	0	0
ITCH	0.026	0.014	-10000	0	-10000	0	0
WWP1	0.02	0.051	-10000	0	-10000	0	0
FYN	0.019	0	-10000	0	-10000	0	0
EGFR	-0.007	0.086	-10000	0	-0.27	32	32
PRL	-0.022	0.082	-10000	0	-0.24	44	44
neuron projection morphogenesis	0.047	0.052	-10000	0	-10000	0	0
PTPRZ1	-0.053	0.17	-10000	0	-0.43	59	59
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.043	0.058	-10000	0	-0.32	1	1
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	0.016	0.061	-10000	0	-0.31	3	3
ADAM17	0.026	0.014	-10000	0	-10000	0	0
ErbB4/ErbB4	0.015	0.067	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.058	0.13	-10000	0	-0.32	48	48
NCOR1	0.019	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	0.026	0.058	-10000	0	-0.36	1	1
GRIN2B	0.011	0.066	-10000	0	-0.31	2	2
ErbB4/ErbB2/betacellulin	0.015	0.056	-10000	0	-10000	0	0
STAT1	0.016	0.041	-10000	0	-0.54	2	2
HBEGF	0.017	0.019	-10000	0	-0.24	2	2
PRLR	-0.047	0.11	-10000	0	-0.24	91	91
E4ICDs/ETO2	-0.007	0.1	-10000	0	-0.3	30	30
axon guidance	0.042	0.06	-10000	0	-10000	0	0
NEDD4	0.024	0.024	-10000	0	-0.24	2	2
Prolactin receptor/Prolactin receptor/Prolactin	-0.044	0.095	-10000	0	-0.3	15	15
CBFA2T3	-0.028	0.15	-10000	0	-0.52	32	32
ErbB4/ErbB2/HBEGF	0.034	0.042	-10000	0	-10000	0	0
MAPK3	0.043	0.053	-10000	0	-0.3	1	1
STAT1 (dimer)	0.019	0.061	-10000	0	-0.29	2	2
MAPK1	0.043	0.053	-10000	0	-0.3	1	1
JAK2	0.009	0.072	-10000	0	-0.5	7	7
ErbB4/ErbB2/neuregulin 1 beta	0.023	0.057	-10000	0	-0.36	1	1
NRG1	0.016	0.053	-10000	0	-0.38	3	3
NRG3	-0.12	0.2	-10000	0	-0.34	142	142
NRG2	0.011	0.057	-10000	0	-0.37	7	7
NRG4	-0.002	0.094	-10000	0	-0.54	11	11
heart development	0.042	0.06	-10000	0	-10000	0	0
neural crest cell migration	0.023	0.057	-10000	0	-0.35	1	1
ERBB2	0.03	0.009	-10000	0	-10000	0	0
WWOX/E4ICDs	0.021	0.057	-10000	0	-10000	0	0
SHC1	0.019	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	0.007	0.089	-10000	0	-0.39	5	5
apoptosis	0.052	0.14	0.37	48	-10000	0	48
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	0.016	0.066	-10000	0	-0.33	3	3
ErbB4/ErbB2/epiregulin	0.021	0.054	-10000	0	-10000	0	0
ErbB4/ErbB4/betacellulin/betacellulin	-0.001	0.07	-10000	0	-10000	0	0
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.007	0.086	-10000	0	-10000	0	0
MDM2	0.018	0.06	-10000	0	-0.24	1	1
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	0.024	0.051	-10000	0	-0.34	1	1
STAT5A	0.046	0.058	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	0.014	0.074	-10000	0	-0.32	2	2
DLG4	0.017	0.029	-10000	0	-0.54	1	1
GRB2/SHC	0.028	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	0.018	0.052	-10000	0	-10000	0	0
STAT5A (dimer)	-0.011	0.058	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.048	0.054	-10000	0	-10000	0	0
LRIG1	0.017	0.029	-10000	0	-0.54	1	1
EREG	-0.009	0.071	-10000	0	-0.24	30	30
BTC	-0.02	0.082	-10000	0	-0.24	43	43
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.042	0.06	-10000	0	-10000	0	0
ERBB4	0.015	0.067	-10000	0	-10000	0	0
STAT5B	0.019	0	-10000	0	-10000	0	0
YAP1	0.015	0.022	-10000	0	-10000	0	0
GRB2	0.019	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0.023	0.069	-10000	0	-0.32	7	7
glial cell differentiation	-0.018	0.052	-10000	0	-10000	0	0
WWOX	0.019	0	-10000	0	-10000	0	0
cell proliferation	0.03	0.062	-10000	0	-0.31	1	1

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.019	0	-9999	-10000	0	0
VLDLR	0.005	0.086	-9999	-0.54	9	9
LRPAP1	0.019	0	-9999	-10000	0	0
NUDC	0.019	0	-9999	-10000	0	0
RELN/LRP8	0	0.066	-9999	-10000	0	0
CaM/Ca2+	0.014	0	-9999	-10000	0	0
KATNA1	0.019	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	0.004	0.056	-9999	-10000	0	0
IQGAP1/CaM	0.028	0	-9999	-10000	0	0
DAB1	-0.027	0.087	-9999	-0.24	51	51
IQGAP1	0.019	0	-9999	-10000	0	0
PLA2G7	-0.13	0.24	-9999	-0.54	96	96
CALM1	0.019	0	-9999	-10000	0	0
DYNLT1	0.019	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	0.028	0	-9999	-10000	0	0
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.019	0	-9999	-10000	0	0
CDK5R1	0.017	0.029	-9999	-0.54	1	1
LIS1/Poliovirus Protein 3A	0.019	0	-9999	-10000	0	0
CDK5R2	-0.044	0.11	-9999	-0.24	85	85
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.034	0.1	-9999	-0.28	34	34
YWHAE	0.019	0	-9999	-10000	0	0
NDEL1/14-3-3 E	0.017	0.061	-9999	-0.27	1	1
MAP1B	0.006	0.017	-9999	-10000	0	0
RAC1	0.025	0	-9999	-10000	0	0
p35/CDK5	0.02	0.054	-9999	-0.34	1	1
RELN	-0.047	0.11	-9999	-0.24	91	91
PAFAH/LIS1	-0.058	0.15	-9999	-0.32	96	96
LIS1/CLIP170	0.033	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.006	0.025	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	0.001	0.073	-9999	-0.29	10	10
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	0.008	0.062	-9999	-0.29	1	1
LIS1/IQGAP1	0.033	0	-9999	-10000	0	0
RHOA	0.025	0	-9999	-10000	0	0
PAFAH1B1	0.026	0	-9999	-10000	0	0
PAFAH1B3	0.017	0.029	-9999	-0.54	1	1
PAFAH1B2	0.019	0	-9999	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0.03	0.012	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	0.025	0.061	-9999	-10000	0	0
LRP8	0.019	0	-9999	-10000	0	0
NDEL1/Katanin 60	0.017	0.061	-9999	-0.27	1	1
P39/CDK5	-0.007	0.072	-9999	-10000	0	0
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.033	0	-9999	-10000	0	0
CDK5	0.011	0.052	-9999	-10000	0	0
PPP2R5D	0.019	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.029	0	-9999	-10000	0	0
CSNK2A1	0.019	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.011	0.09	-9999	-0.32	9	9
RELN/VLDLR	0.005	0.079	-9999	-0.3	9	9
CDC42	0.025	0	-9999	-10000	0	0

×

Regulation of Androgen receptor activity

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
HDAC1	0.025	0.021	-9999	-0.38	1	1
SMARCC1	0.019	0.017	-9999	-10000	0	0
REL	0.019	0.001	-9999	-10000	0	0
HDAC7	0.036	0.072	-9999	-0.25	3	3
JUN	-0.007	0.078	-9999	-0.24	36	36
EP300	0.019	0	-9999	-10000	0	0
KAT2B	0.016	0.041	-9999	-0.54	2	2
KAT5	0.019	0	-9999	-10000	0	0
MAPK14	0.018	0.057	-9999	-0.38	7	7
FOXO1	0.019	0	-9999	-10000	0	0
T-DHT/AR	0.042	0.08	-9999	-0.26	4	4
MAP2K6	0.008	0.076	-9999	-0.54	7	7
BRM/BAF57	0.027	0.021	-9999	-0.38	1	1
MAP2K4	0.019	0.005	-9999	-10000	0	0
SMARCA2	0.017	0.029	-9999	-0.54	1	1
PDE9A	0.007	0.14	-9999	-1.1	3	3
NCOA2	0.018	0.014	-9999	-0.24	1	1
CEBPA	-0.028	0.16	-9999	-0.54	31	31
EHMT2	0.019	0	-9999	-10000	0	0
cell proliferation	0.056	0.078	-9999	-10000	0	0
NR0B1	0	0	-9999	-10000	0	0
EGR1	-0.003	0.072	-9999	-0.24	30	30
RXRs/9cRA	-0.036	0.14	-9999	-0.29	82	82
AR/RACK1/Src	0.027	0.061	-9999	-0.27	6	6
AR/GR	0.007	0.051	-9999	-0.24	2	2
GNB2L1	0.019	0.002	-9999	-10000	0	0
PKN1	0.017	0.029	-9999	-0.54	1	1
RCHY1	0.019	0	-9999	-10000	0	0
epidermal growth factor receptor activity	-0.001	0.002	-9999	-10000	0	0
MAPK8	0.025	0.01	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	0.034	0.061	-9999	-0.26	7	7
SRC	0.031	0.046	-9999	-0.25	7	7
NR3C1	0.019	0	-9999	-10000	0	0
KLK3	-0.03	0.042	-9999	-10000	0	0
APPBP2	0.019	0.005	-9999	-10000	0	0
TRIM24	0.019	0	-9999	-10000	0	0
T-DHT/AR/TIP60	0.026	0.055	-9999	-0.28	7	7
TMPRSS2	-0.009	0.23	-9999	-1.1	15	15
RXRG	-0.11	0.23	-9999	-0.54	82	82
mol:9cRA	0	0	-9999	-10000	0	0
RXRA	0.019	0	-9999	-10000	0	0
RXRB	0.019	0	-9999	-10000	0	0
CARM1	0.018	0.002	-9999	-10000	0	0
NR2C2	0.019	0	-9999	-10000	0	0
KLK2	0.012	0.1	-9999	-0.41	2	2
AR	-0.003	0.058	-9999	-0.2	7	7
SENP1	0.019	0	-9999	-10000	0	0
HSP90AA1	0.017	0.029	-9999	-0.54	1	1
MDM2	0.015	0.033	-9999	-0.24	6	6
SRY	-0.001	0.026	-9999	-0.24	4	4
GATA2	0.014	0.036	-9999	-0.24	7	7
MYST2	0.019	0	-9999	-10000	0	0
HOXB13	-0.14	0.13	-9999	-0.24	218	218
T-DHT/AR/RACK1/Src	0.029	0.057	-9999	-0.26	7	7
positive regulation of transcription	0.014	0.036	-9999	-0.24	7	7
DNAJA1	0.019	0.005	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.031	0.019	-9999	-0.22	1	1
NCOA1	0.023	0.002	-9999	-10000	0	0
SPDEF	-0.029	0.098	-9999	-0.24	63	63
T-DHT/AR/TIF2	0.041	0.04	-9999	-10000	0	0
T-DHT/AR/Hsp90	0.025	0.056	-9999	-0.27	8	8
GSK3B	0.019	0.002	-9999	-10000	0	0
NR2C1	0.019	0	-9999	-10000	0	0
mol:T-DHT	0.027	0.048	-9999	-0.28	7	7
SIRT1	0.019	0	-9999	-10000	0	0
ZMIZ2	0.019	0	-9999	-10000	0	0
POU2F1	0.026	0.027	-9999	-10000	0	0
T-DHT/AR/DAX-1	0.014	0.053	-9999	-0.28	7	7
CREBBP	0.019	0	-9999	-10000	0	0
SMARCE1	0.019	0	-9999	-10000	0	0

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	-0.033	0.12	-9999	-0.29	61	61
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.017	0.029	-9999	-0.54	1	1
TCEB1	0.019	0	-9999	-10000	0	0
HIF1A/p53	0.036	0.026	-9999	-0.44	1	1
HIF1A	0.025	0.027	-9999	-0.48	1	1
COPS5	0.019	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.055	0.016	-9999	-0.26	1	1
FIH (dimer)	0.017	0.029	-9999	-0.54	1	1
CDKN2A	-0.11	0.14	-9999	-0.25	171	171
ARNT/IPAS	-0.008	0.086	-9999	-0.38	9	9
HIF1AN	0.017	0.029	-9999	-0.54	1	1
GNB2L1	0.019	0	-9999	-10000	0	0
HIF1A/ARNT	0.036	0.026	-9999	-0.44	1	1
CUL2	0.019	0	-9999	-10000	0	0
OS9	0.018	0.014	-9999	-0.24	1	1
RACK1/Elongin B/Elongin C	0.037	0.019	-9999	-0.32	1	1
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.035	0.03	-9999	-0.34	2	2
PHD1-3/OS9	0.046	0.027	-9999	-0.28	2	2
HIF1A/RACK1/Elongin B/Elongin C	0.051	0.029	-9999	-0.41	1	1
VHL	0.019	0	-9999	-10000	0	0
HSP90AA1	0.017	0.029	-9999	-0.54	1	1
HIF1A/JAB1	0.036	0.026	-9999	-0.44	1	1
EGLN3	0.014	0.045	-9999	-0.39	4	4
EGLN2	0.019	0	-9999	-10000	0	0
EGLN1	0.019	0	-9999	-10000	0	0
TP53	0.019	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.047	0.014	-9999	-10000	0	0
ARNT	0.019	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.019	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.018	0.066	-9999	-0.3	5	5

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0.009	0.064	-10000	0	-0.27	11	11
MAPK9	0.01	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	0	0	-10000	0	-10000	0	0
GNB1/GNG2	0.02	0.044	-10000	0	-0.32	6	6
GNB1	0.019	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.01	0	-10000	0	-10000	0	0
Gs family/GTP	-0.008	0.055	-10000	0	-0.14	49	49
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	0.005	0.014	0.04	49	-10000	0	49
GNAL	-0.02	0.1	-10000	0	-0.27	49	49
GNG2	0.01	0.071	-10000	0	-0.54	6	6
CRH	0	0	-10000	0	-10000	0	0
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.01	0.001	-10000	0	-10000	0	0
MAPK11	0.01	0	-10000	0	-10000	0	0

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.008	0.07	-9999	-0.41	3	3
PDGFB-D/PDGFRB/SLAP	-0.051	0.16	-9999	-0.39	68	68
PDGFB-D/PDGFRB/APS/CBL	0.03	0.052	-9999	-0.32	7	7
AKT1	0.054	0.019	-9999	-10000	0	0
mol:PI-4-5-P2	0	0.001	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	-0.011	0.07	-9999	-0.41	3	3
PIK3CA	0.018	0.014	-9999	-0.24	1	1
FGR	-0.048	0.17	-9999	-0.56	36	36
mol:Ca2+	-0.018	0.06	-9999	-10000	0	0
MYC	-0.014	0.085	-9999	-0.36	3	3
SHC1	0.019	0	-9999	-10000	0	0
HRAS/GDP	0.04	0.021	-9999	-0.26	1	1
LRP1/PDGFRB/PDGFB	0.034	0.029	-9999	-0.24	2	2
GRB10	0.017	0.019	-9999	-0.24	2	2
PTPN11	0.019	0	-9999	-10000	0	0
GO:0007205	-0.018	0.061	-9999	-10000	0	0
PTEN	0.017	0.029	-9999	-0.54	1	1
GRB2	0.019	0	-9999	-10000	0	0
GRB7	-0.003	0.067	-9999	-0.24	26	26
PDGFB-D/PDGFRB/SHP2	0.026	0.021	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB10	0.025	0.025	-9999	-10000	0	0
cell cycle arrest	-0.051	0.16	-9999	-0.39	68	68
HRAS	0.019	0	-9999	-10000	0	0
HIF1A	0.057	0.018	-9999	-10000	0	0
GAB1	-0.045	0.095	-9999	-0.37	5	5
mol:GTP	0	0	-9999	-10000	0	0
DNM2	-0.034	0.088	-9999	-0.4	3	3
PDGFB-D/PDGFRB	0.043	0.019	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.026	0.021	-9999	-10000	0	0
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.025	0.075	-9999	-0.48	3	3
positive regulation of MAPKKK cascade	0.026	0.021	-9999	-10000	0	0
PIK3R1	0.019	0	-9999	-10000	0	0
mol:IP3	-0.018	0.061	-9999	-10000	0	0
E5	-0.001	0.002	-9999	-10000	0	0
CSK	0.019	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	0.01	0.051	-9999	-0.3	1	1
SHB	0.006	0.071	-9999	-0.33	14	14
BLK	-0.34	0.26	-9999	-0.53	235	235
PTPN2	0.019	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.026	0.021	-9999	-10000	0	0
BCAR1	0.019	0	-9999	-10000	0	0
VAV2	-0.042	0.11	-9999	-0.41	6	6
CBL	0.019	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.026	0.021	-9999	-10000	0	0
LCK	-0.2	0.26	-9999	-0.53	141	141
PDGFRB	0.016	0.031	-9999	-0.24	5	5
ACP1	0.019	0	-9999	-10000	0	0
HCK	-0.031	0.16	-9999	-0.56	31	31
ABL1	-0.065	0.11	-9999	-0.34	27	27
PDGFB-D/PDGFRB/CBL	-0.053	0.1	-9999	-0.43	4	4
PTPN1	0.019	0.001	-9999	-10000	0	0
SNX15	0.019	0	-9999	-10000	0	0
STAT3	0.019	0	-9999	-10000	0	0
STAT1	0.016	0.041	-9999	-0.54	2	2
cell proliferation	-0.013	0.081	-9999	-0.34	3	3
SLA	-0.084	0.22	-9999	-0.54	68	68
actin cytoskeleton reorganization	0.048	0.038	-9999	-0.24	3	3
SRC	0.006	0.018	-9999	-10000	0	0
PI3K	-0.002	0.013	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	0.023	0.044	-9999	-0.24	1	1
SH2B2	0.008	0.076	-9999	-0.54	7	7
PLCgamma1/SPHK1	-0.011	0.072	-9999	-0.42	3	3
LYN	-0.013	0.11	-9999	-0.56	15	15
LRP1	0.015	0.033	-9999	-0.24	6	6
SOS1	0.019	0	-9999	-10000	0	0
STAT5B	0.019	0	-9999	-10000	0	0
STAT5A	0.017	0.029	-9999	-0.54	1	1
NCK1-2/p130 Cas	0.061	0.016	-9999	-10000	0	0
SPHK1	0.011	0.059	-9999	-0.36	8	8
EDG1	0	0.002	-9999	-10000	0	0
mol:DAG	-0.018	0.061	-9999	-10000	0	0
PLCG1	-0.018	0.062	-9999	-10000	0	0
NHERF/PDGFRB	0.036	0.019	-9999	-10000	0	0
YES1	0.008	0.018	-9999	-10000	0	0
cell migration	0.036	0.019	-9999	-10000	0	0
SHC/Grb2/SOS1	0.061	0.016	-9999	-10000	0	0
SLC9A3R2	0.018	0.014	-9999	-0.24	1	1
SLC9A3R1	0.019	0	-9999	-10000	0	0
NHERF1-2/PDGFRB/PTEN	0.046	0.025	-9999	-0.28	1	1
FYN	0.009	0.018	-9999	-10000	0	0
DOK1	0.033	0.015	-9999	-10000	0	0
HRAS/GTP	0.014	0	-9999	-10000	0	0
PDGFB	0.019	0	-9999	-10000	0	0
RAC1	-0.03	0.1	-9999	-0.4	5	5
PRKCD	0.033	0.016	-9999	-10000	0	0
FER	0.033	0.016	-9999	-10000	0	0
MAPKKK cascade	-0.001	0.01	-9999	-10000	0	0
RASA1	0.032	0.023	-9999	-0.29	1	1
NCK1	0.019	0	-9999	-10000	0	0
NCK2	0.019	0	-9999	-10000	0	0
p62DOK/Csk	0.045	0.014	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHB	0.016	0.056	-9999	-0.39	4	4
chemotaxis	-0.064	0.11	-9999	-0.32	31	31
STAT1-3-5/STAT1-3-5	0.033	0.035	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0.011	0.02	-9999	-0.16	5	5
PTPRJ	0.019	0	-9999	-10000	0	0

×

Regulation of nuclear SMAD2/3 signaling

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
EP300	0.021	0.008	-10000	0	-10000	0	0
HSPA8	0.018	0.002	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	0.055	0.072	-10000	0	-0.35	7	7
AKT1	0.019	0.013	-10000	0	-10000	0	0
GSC	-0.024	0.12	-10000	0	-10000	0	0
NKX2-5	-0.11	0.22	-10000	0	-0.49	87	87
muscle cell differentiation	-0.004	0.063	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1	0.073	0.06	-10000	0	-10000	0	0
SMAD4	0.027	0.028	-10000	0	-10000	0	0
CBFB	0.019	0	-10000	0	-10000	0	0
SAP18	0.019	0.001	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.018	0.08	-10000	0	-0.31	16	16
SMAD3/SMAD4/VDR	0.073	0.037	-10000	0	-0.26	2	2
MYC	0.017	0.027	-10000	0	-0.25	3	3
CDKN2B	0	0.18	-10000	0	-1.4	5	5
AP1	0.038	0.089	-10000	0	-0.31	6	6
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.069	0.019	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.042	0.055	-10000	0	-0.28	5	5
SP3	0.022	0	-10000	0	-10000	0	0
CREB1	0.019	0	-10000	0	-10000	0	0
FOXH1	0.012	0.03	-10000	0	-0.25	3	3
SMAD3/SMAD4/GR	0.054	0.033	-10000	0	-10000	0	0
GATA3	-0.11	0.24	-10000	0	-0.56	80	80
SKI/SIN3/HDAC complex/NCoR1	0.053	0.012	-10000	0	-10000	0	0
MEF2C/TIF2	-0.009	0.12	-10000	0	-0.4	5	5
endothelial cell migration	-0.001	0.1	1.4	1	-10000	0	1
MAX	0.018	0.006	-10000	0	-10000	0	0
RBBP7	0.019	0.001	-10000	0	-10000	0	0
RBBP4	0.019	0.001	-10000	0	-10000	0	0
RUNX2	0.015	0.043	-10000	0	-0.44	3	3
RUNX3	-0.018	0.14	-10000	0	-0.54	24	24
RUNX1	0.014	0.05	-10000	0	-0.54	3	3
CTBP1	0.019	0	-10000	0	-10000	0	0
NR3C1	0.018	0.006	-10000	0	-10000	0	0
VDR	0.016	0.041	-10000	0	-0.54	2	2
CDKN1A	0.057	0.046	-10000	0	-10000	0	0
KAT2B	0.016	0.041	-10000	0	-0.53	2	2
SMAD2/SMAD2/SMAD4/FOXH1	0.042	0.051	-10000	0	-10000	0	0
DCP1A	0.019	0	-10000	0	-10000	0	0
SKI	0.019	0.001	-10000	0	-10000	0	0
SERPINE1	-0.003	0.1	-10000	0	-1.4	1	1
SMAD3/SMAD4/ATF2	0.054	0.033	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	0.052	0.04	-10000	0	-10000	0	0
SAP30	0.019	0.001	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.044	0.02	-10000	0	-10000	0	0
JUN	0.032	0.087	-10000	0	-0.31	6	6
SMAD3/SMAD4/IRF7	0.05	0.057	-10000	0	-0.34	5	5
TFE3	0.025	0.007	-10000	0	-10000	0	0
COL1A2	-0.042	0.1	-10000	0	-10000	0	0
mesenchymal cell differentiation	-0.051	0.045	0.35	2	-10000	0	2
DLX1	-0.035	0.14	-10000	0	-0.35	53	53
TCF3	0.019	0	-10000	0	-10000	0	0
FOS	0.013	0.05	-10000	0	-0.26	11	11
SMAD3/SMAD4/Max	0.054	0.033	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.04	0.007	-10000	0	-10000	0	0
ZBTB17	0.019	0.01	-10000	0	-10000	0	0
LAMC1	0.056	0.031	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.054	0.033	-10000	0	-10000	0	0
IRF7	0.012	0.065	-10000	0	-0.54	5	5
ESR1	0.011	0.077	-10000	0	-0.54	7	7
HNF4A	-0.014	0.073	-10000	0	-0.24	33	33
MEF2C	-0.021	0.13	-10000	0	-0.33	15	15
SMAD2-3/SMAD4	0.055	0.043	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.042	0.012	-10000	0	-10000	0	0
IGHV3OR16-13	-0.002	0.019	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.019	0	-10000	0	-10000	0	0
CREBBP	0.02	0.005	-10000	0	-10000	0	0
SKIL	0.019	0	-10000	0	-10000	0	0
HDAC1	0.017	0.029	-10000	0	-0.54	1	1
HDAC2	0.019	0.001	-10000	0	-10000	0	0
SNIP1	0.018	0.002	-10000	0	-10000	0	0
GCN5L2	0.002	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.068	0.037	-10000	0	-10000	0	0
MSG1/HSC70	-0.001	0.091	-10000	0	-0.38	16	16
SMAD2	0.016	0.02	-10000	0	-10000	0	0
SMAD3	0.029	0.025	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.049	0.045	-10000	0	-0.25	3	3
SMAD2/SMAD2/SMAD4	0.015	0.029	-10000	0	-0.32	2	2
NCOR1	0.019	0.001	-10000	0	-10000	0	0
NCOA2	0.018	0.014	-10000	0	-0.24	1	1
NCOA1	0.019	0	-10000	0	-10000	0	0
MYOD/E2A	0.019	0.023	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.082	0.058	-10000	0	-10000	0	0
IFNB1	0.035	0.051	-10000	0	-0.29	5	5
SMAD3/SMAD4/MEF2C	0.005	0.13	-10000	0	-0.47	3	3
CITED1	-0.02	0.12	-10000	0	-0.37	36	36
SMAD2-3/SMAD4/ARC105	0.065	0.04	-10000	0	-10000	0	0
RBL1	0.019	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.053	0.076	-10000	0	-0.47	5	5
RUNX1-3/PEBPB2	0.013	0.098	-10000	0	-0.34	25	25
SMAD7	0.075	0.07	-10000	0	-10000	0	0
MYC/MIZ-1	0.026	0.029	-10000	0	-10000	0	0
SMAD3/SMAD4	0.048	0.062	-10000	0	-0.39	1	1
IL10	-0.051	0.23	-10000	0	-0.62	35	35
PIASy/HDAC complex	0.017	0.006	-10000	0	-10000	0	0
PIAS3	0.02	0.003	-10000	0	-10000	0	0
CDK2	0.02	0.005	-10000	0	-10000	0	0
IL5	-0.043	0.17	-10000	0	-0.38	50	50
CDK4	0.019	0.021	-10000	0	-0.25	2	2
PIAS4	0.017	0.006	-10000	0	-10000	0	0
ATF3	0.015	0.03	-10000	0	-0.24	5	5
SMAD3/SMAD4/SP1	0.059	0.052	-10000	0	-10000	0	0
FOXG1	-0.022	0.085	-10000	0	-0.24	46	46
FOXO3	0.027	0.017	-10000	0	-10000	0	0
FOXO1	0.027	0.017	-10000	0	-10000	0	0
FOXO4	0.027	0.017	-10000	0	-10000	0	0
heart looping	-0.02	0.12	-10000	0	-0.33	15	15
CEBPB	0.019	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	0.018	0.1	-10000	0	-0.32	20	20
MYOD1	0.006	0.034	-10000	0	-0.24	6	6
SMAD3/SMAD4/HNF4	0.032	0.059	-10000	0	-0.24	2	2
SMAD3/SMAD4/GATA3	-0.036	0.2	-10000	0	-0.38	84	84
SnoN/SIN3/HDAC complex/NCoR1	0.019	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.049	0.095	-10000	0	-0.28	25	25
SMAD3/SMAD4/SP1-3	0.077	0.047	-10000	0	-10000	0	0
MED15	0.019	0	-10000	0	-10000	0	0
SP1	0.017	0.027	-10000	0	-10000	0	0
SIN3B	0.019	0.001	-10000	0	-10000	0	0
SIN3A	0.019	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.019	0.14	-10000	0	-0.27	74	74
ITGB5	0.058	0.037	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.054	0.011	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.014	0.087	-10000	0	-0.23	3	3
AR	-0.085	0.13	-10000	0	-0.24	143	143
negative regulation of cell growth	0.058	0.04	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	0.045	0.04	-10000	0	-10000	0	0
E2F5	0.007	0.081	-10000	0	-0.54	8	8
E2F4	0.019	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.06	0.042	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4	0.054	0.057	-10000	0	-0.31	5	5
TFDP1	0.019	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.051	0.095	-10000	0	-0.31	6	6
SMAD3/SMAD4/RUNX2	0.051	0.045	-10000	0	-0.35	2	2
TGIF2	0.019	0	-10000	0	-10000	0	0
TGIF1	0.019	0	-10000	0	-10000	0	0
ATF2	0.019	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.021	0.14	-9999	-0.31	75	75
Ran/GTP/Exportin 1/HDAC1	-0.001	0.012	-9999	-0.23	1	1
NF kappa B1 p50/RelA/I kappa B alpha	-0.012	0.14	-9999	-0.28	75	75
SUMO1	0.019	0	-9999	-10000	0	0
ZFPM1	0.017	0.032	-9999	-0.39	2	2
NPC/RanGAP1/SUMO1/Ubc9	0.025	0	-9999	-10000	0	0
FKBP3	0.019	0	-9999	-10000	0	0
Histones	0.02	0.078	-9999	-0.23	1	1
YY1/LSF	0.03	0.053	-9999	-0.28	10	10
SMG5	0.019	0	-9999	-10000	0	0
RAN	0.019	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	-0.017	0.11	-9999	-0.24	75	75
I kappa B alpha/HDAC1	-0.001	0.083	-9999	-0.27	1	1
SAP18	0.019	0	-9999	-10000	0	0
RELA	-0.01	0.11	-9999	-0.22	75	75
HDAC1/Smad7	0.037	0.019	-9999	-0.32	1	1
RANGAP1	0.019	0	-9999	-10000	0	0
HDAC3/TR2	0	0.082	-9999	-10000	0	0
NuRD/MBD3 Complex	0.054	0.018	-9999	-10000	0	0
NF kappa B1 p50/RelA	0	0.099	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	0.014	0.036	-9999	-0.24	7	7
GATA1	0	0	-9999	-10000	0	0
Mad/Max	0.028	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.059	0.027	-9999	-0.35	1	1
RBBP7	0.019	0	-9999	-10000	0	0
NPC	0.011	0	-9999	-10000	0	0
RBBP4	0.019	0	-9999	-10000	0	0
MAX	0.019	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.019	0	-9999	-10000	0	0
NFKBIA	-0.012	0.09	-9999	-10000	0	0
KAT2B	0.016	0.041	-9999	-0.54	2	2
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.05	0.012	-9999	-10000	0	0
SIN3 complex	0.049	0	-9999	-10000	0	0
SMURF1	0.019	0	-9999	-10000	0	0
CHD3	0.019	0	-9999	-10000	0	0
SAP30	0.019	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.019	0	-9999	-10000	0	0
YY1/HDAC3	0.012	0.077	-9999	-0.35	1	1
YY1/HDAC2	0.037	0.019	-9999	-0.22	2	2
YY1/HDAC1	0.036	0.026	-9999	-0.25	3	3
NuRD/MBD2 Complex (MeCP1)	0.055	0.011	-9999	-10000	0	0
PPARG	-0.03	0.14	-9999	-0.3	79	79
HDAC8/hEST1B	0.038	0	-9999	-10000	0	0
UBE2I	0.019	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.019	0	-9999	-10000	0	0
TNFRSF1A	0.019	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	0	0.082	-9999	-10000	0	0
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.037	0.018	-9999	-0.32	1	1
CREBBP	0.019	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.058	0.019	-9999	-10000	0	0
HDAC1	0.017	0.029	-9999	-0.54	1	1
HDAC3	-0.012	0.09	-9999	-10000	0	0
HDAC2	0.019	0	-9999	-10000	0	0
YY1	0.033	0.022	-9999	-0.27	2	2
HDAC8	0.019	0	-9999	-10000	0	0
SMAD7	0.019	0	-9999	-10000	0	0
NCOR2	0.019	0	-9999	-10000	0	0
MXD1	0.019	0	-9999	-10000	0	0
STAT3	0.031	0	-9999	-10000	0	0
NFKB1	0.019	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.019	0	-9999	-10000	0	0
YY1/LSF/HDAC1	0.039	0.052	-9999	-0.27	9	9
YY1/SAP30/HDAC1	0.046	0.024	-9999	-0.27	1	1
EP300	0.019	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.031	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.012	0.089	-9999	-10000	0	0
histone deacetylation	0.054	0.01	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.011	0.075	-9999	-10000	0	0
nuclear export	-0.038	0	-9999	-10000	0	0
PRKACA	0.019	0	-9999	-10000	0	0
GATAD2B	0.019	0	-9999	-10000	0	0
GATAD2A	0.019	0	-9999	-10000	0	0
GATA2/HDAC3	-0.003	0.084	-9999	-0.28	2	2
GATA1/HDAC1	0.013	0.021	-9999	-0.39	1	1
GATA1/HDAC3	-0.013	0.079	-9999	-10000	0	0
CHD4	0.019	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.056	0.16	-9999	-0.38	75	75
SIN3/HDAC complex/Mad/Max	0.055	0.011	-9999	-10000	0	0
NuRD Complex	0.063	0.019	-9999	-10000	0	0
positive regulation of chromatin silencing	0.018	0.076	-9999	-0.23	1	1
SIN3B	0.019	0	-9999	-10000	0	0
MTA2	0.019	0	-9999	-10000	0	0
SIN3A	0.019	0	-9999	-10000	0	0
XPO1	0.019	0	-9999	-10000	0	0
SUMO1/HDAC1	0.039	0.015	-9999	-0.25	1	1
HDAC complex	0.048	0.017	-9999	-0.28	1	1
GATA1/Fog1	0.012	0.023	-9999	-0.39	1	1
FKBP25/HDAC1/HDAC2	0.037	0.019	-9999	-0.32	1	1
TNF	-0.095	0.22	-9999	-0.54	75	75
negative regulation of cell growth	0.054	0.01	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.055	0.011	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.043	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.023	0.14	-9999	-0.3	75	75
SIN3/HDAC complex/NCoR1	0.052	0.01	-9999	-10000	0	0
TFCP2	0.006	0.082	-9999	-0.5	9	9
NR2C1	0.019	0	-9999	-10000	0	0
MBD3	0.016	0.041	-9999	-0.54	2	2
MBD2	0.019	0	-9999	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.02	0.059	-9999	-0.32	11	11
SNTA1	0.014	0.036	-9999	-0.24	7	7
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.019	0.062	-9999	-0.32	12	12
MAPK12	0.02	0.06	-9999	-0.3	12	12
CCND1	0.016	0.033	-9999	-0.21	2	2
p38 gamma/SNTA1	0.027	0.059	-9999	-0.27	12	12
MAP2K3	0.019	0	-9999	-10000	0	0
PKN1	0.017	0.029	-9999	-0.54	1	1
G2/M transition checkpoint	0.02	0.06	-9999	-0.3	12	12
MAP2K6	0.018	0.049	-9999	-0.31	8	8
MAPT	-0.03	0.072	-9999	-0.27	15	15
MAPK13	0.014	0.07	-9999	-0.38	11	11
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.019	0.019	-9999	-0.33	1	1

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.007	0.15	-9999	-0.93	4	4
MKNK1	0.019	0	-9999	-10000	0	0
MAPK14	0.008	0.066	-9999	-0.28	5	5
ATF2/c-Jun	0.007	0.095	-9999	-0.32	10	10
MAPK11	0.008	0.066	-9999	-0.28	5	5
MITF	0.006	0.11	-9999	-0.38	20	20
MAPKAPK5	0.021	0.073	-9999	-0.32	5	5
KRT8	-0.035	0.14	-9999	-0.32	61	61
MAPKAPK3	0.019	0	-9999	-10000	0	0
MAPKAPK2	0.019	0	-9999	-10000	0	0
p38alpha-beta/CK2	0.013	0.093	-9999	-0.33	12	12
CEBPB	0.021	0.073	-9999	-0.32	5	5
SLC9A1	0.021	0.073	-9999	-0.32	5	5
mol:GDP	0	0	-9999	-10000	0	0
ATF2	0.02	0.081	-9999	-0.33	5	5
p38alpha-beta/MNK1	0.028	0.075	-9999	-0.32	5	5
JUN	0.006	0.095	-9999	-0.32	10	10
PPARGC1A	-0.038	0.11	-9999	-0.36	17	17
USF1	0.021	0.073	-9999	-0.32	5	5
RAB5/GDP/GDI1	0.021	0.05	-9999	-0.24	4	4
NOS2	0.012	0.11	-9999	-0.62	3	3
DDIT3	0.021	0.074	-9999	-0.32	5	5
RAB5A	0.019	0	-9999	-10000	0	0
HSPB1	0.025	0.058	-9999	-0.27	4	4
p38alpha-beta/HBP1	0.028	0.075	-9999	-0.32	5	5
CREB1	0.025	0.075	-9999	-0.32	6	6
RAB5/GDP	0.014	0	-9999	-10000	0	0
EIF4E	0.025	0.061	-9999	-0.28	4	4
RPS6KA4	0.021	0.073	-9999	-0.32	5	5
PLA2G4A	0.02	0.073	-9999	-0.29	11	11
GDI1	0.021	0.073	-9999	-0.32	5	5
TP53	0.017	0.086	-9999	-0.4	5	5
RPS6KA5	0.019	0.078	-9999	-0.33	7	7
ESR1	0.014	0.096	-9999	-0.39	12	12
HBP1	0.019	0	-9999	-10000	0	0
MEF2C	0.019	0.077	-9999	-0.31	7	7
MEF2A	0.021	0.073	-9999	-0.32	5	5
EIF4EBP1	0.025	0.076	-9999	-0.33	6	6
KRT19	0.001	0.085	-9999	-0.33	7	7
ELK4	0.021	0.073	-9999	-0.32	5	5
ATF6	0.021	0.073	-9999	-0.32	5	5
ATF1	0.025	0.075	-9999	-0.32	6	6
p38alpha-beta/MAPKAPK2	0.028	0.075	-9999	-0.32	5	5
p38alpha-beta/MAPKAPK3	0.028	0.075	-9999	-0.32	5	5

×

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	0.018	0.13	-9999	-1.2	2	2
RAD9A	0.019	0	-9999	-10000	0	0
AP1	0.007	0.067	-9999	-0.3	6	6
IFNAR2	0.02	0.004	-9999	-10000	0	0
AKT1	0.019	0.034	-9999	-0.23	3	3
ER alpha/Oestrogen	0.007	0.056	-9999	-0.39	7	7
NFX1/SIN3/HDAC complex	0.055	0.013	-9999	-10000	0	0
EGF	-0.031	0.15	-9999	-0.42	41	41
SMG5	0.019	0	-9999	-10000	0	0
SMG6	0.019	0	-9999	-10000	0	0
SP3/HDAC2	0.031	0.008	-9999	-10000	0	0
TERT/c-Abl	0.027	0.12	-9999	-1.1	2	2
SAP18	0.019	0.001	-9999	-10000	0	0
MRN complex	0.036	0.026	-9999	-0.32	2	2
WT1	0.002	0.004	-9999	-10000	0	0
WRN	0.019	0	-9999	-10000	0	0
SP1	0.021	0.006	-9999	-10000	0	0
SP3	0.02	0.002	-9999	-10000	0	0
TERF2IP	0.019	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.008	0.092	-9999	-0.94	2	2
Mad/Max	0.03	0.005	-9999	-10000	0	0
TERT	0.015	0.13	-9999	-1.3	2	2
CCND1	0.023	0.12	-9999	-0.99	2	2
MAX	0.02	0.002	-9999	-10000	0	0
RBBP7	0.019	0.001	-9999	-10000	0	0
RBBP4	0.019	0.001	-9999	-10000	0	0
TERF2	0.017	0	-9999	-10000	0	0
PTGES3	0.019	0	-9999	-10000	0	0
SIN3A	0.019	0.001	-9999	-10000	0	0
Telomerase/911	0.051	0.023	-9999	-10000	0	0
CDKN1B	-0.12	0.2	-9999	-0.33	154	154
RAD1	0.019	0	-9999	-10000	0	0
XRCC5	0.019	0	-9999	-10000	0	0
XRCC6	0.019	0	-9999	-10000	0	0
SAP30	0.019	0.001	-9999	-10000	0	0
TRF2/PARP2	0.028	0	-9999	-10000	0	0
UBE3A	0.019	0.002	-9999	-10000	0	0
JUN	-0.006	0.078	-9999	-0.24	36	36
E6	0.001	0.002	-9999	-10000	0	0
HPV-16 E6/E6AP	0.016	0.005	-9999	-10000	0	0
FOS	0.012	0.045	-9999	-0.24	11	11
IFN-gamma/IRF1	-0.15	0.23	-9999	-0.4	154	154
PARP2	0.019	0	-9999	-10000	0	0
BLM	0.019	0	-9999	-10000	0	0
Telomerase	0.069	0.069	-9999	-0.34	4	4
IRF1	-0.041	0.18	-9999	-0.53	43	43
ESR1	0.009	0.076	-9999	-0.54	7	7
KU/TER	0.028	0	-9999	-10000	0	0
ATM/TRF2	0.029	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.061	0.013	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.061	0.013	-9999	-10000	0	0
HDAC1	0.018	0.029	-9999	-0.54	1	1
HDAC2	0.021	0.005	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.023	0.03	-9999	-0.38	2	2
ABL1	0.019	0	-9999	-10000	0	0
MXD1	0.02	0.002	-9999	-10000	0	0
MRE11A	0.019	0	-9999	-10000	0	0
HUS1	0.019	0	-9999	-10000	0	0
RPS6KB1	0.019	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	0.044	0.12	-9999	-0.71	4	4
NR2F2	0.017	0.004	-9999	-10000	0	0
MAPK3	0.018	0.011	-9999	-10000	0	0
MAPK1	0.018	0.011	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.015	0.041	-9999	-0.54	2	2
NFKB1	0.019	0	-9999	-10000	0	0
HNRNPC	0.019	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	0.019	0	-9999	-10000	0	0
EGFR	-0.006	0.086	-9999	-0.27	32	32
mol:Oestrogen	0	0.001	-9999	-10000	0	0
EGF/EGFR	-0.024	0.12	-9999	-0.38	31	31
MYC	0.018	0.024	-9999	-0.24	3	3
IL2	0.007	0.017	-9999	-0.24	1	1
KU	0.028	0	-9999	-10000	0	0
RAD50	0.016	0.041	-9999	-0.54	2	2
HSP90AA1	0.017	0.029	-9999	-0.54	1	1
TGFB1	0.015	0.041	-9999	-0.54	2	2
TRF2/BLM	0.028	0	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	0.036	0.12	-9999	-1.1	2	2
SP1/HDAC2	0.033	0.011	-9999	-10000	0	0
PINX1	0.018	0.014	-9999	-0.24	1	1
Telomerase/EST1A	-0.008	0.092	-9999	-0.94	2	2
Smad3/Myc	0.029	0.029	-9999	-0.32	2	2
911 complex	0.038	0	-9999	-10000	0	0
IFNG	-0.17	0.26	-9999	-0.53	128	128
Telomerase/PinX1	-0.008	0.092	-9999	-0.94	2	2
Telomerase/AKT1/mTOR/p70S6K	0.043	0.04	-9999	-0.29	1	1
SIN3B	0.019	0.001	-9999	-10000	0	0
YWHAE	0.019	0	-9999	-10000	0	0
Telomerase/EST1B	-0.008	0.092	-9999	-0.94	2	2
response to DNA damage stimulus	0.004	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0.053	0.022	-9999	-0.25	2	2
TRF2/WRN	0.028	0	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.008	0.092	-9999	-0.94	2	2
E2F1	0.02	0.004	-9999	-10000	0	0
ZNFX1	0.019	0.001	-9999	-10000	0	0
PIF1	0.014	0.05	-9999	-0.54	3	3
NCL	0.019	0	-9999	-10000	0	0
DKC1	0.019	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

Insulin 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
CBL/APS/CAP	-0.013	0.045	-9999	-0.24	11	11
TC10/GTP	-0.007	0.039	-9999	-0.23	11	11
Insulin Receptor/Insulin/IRS1/Shp2	0.028	0.04	-9999	-10000	0	0
HRAS	0.019	0	-9999	-10000	0	0
APS homodimer	0.008	0.076	-9999	-0.54	7	7
GRB14	-0.026	0.095	-9999	-0.24	59	59
FOXO3	0.028	0.012	-9999	-10000	0	0
AKT1	0.025	0.05	-9999	-10000	0	0
INSR	0.02	0.014	-9999	-0.24	1	1
Insulin Receptor/Insulin	0.046	0.006	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.017	0.019	-9999	-0.24	2	2
SORBS1	0.012	0.059	-9999	-0.48	5	5
CRK	0.019	0	-9999	-10000	0	0
PTPN1	0.035	0.005	-9999	-10000	0	0
CAV1	0.02	0.034	-9999	-10000	0	0
CBL/APS/CAP/Crk-II/C3G	0.047	0.054	-9999	-0.26	11	11
Insulin Receptor/Insulin/IRS1/NCK2	0.028	0.04	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.024	0.032	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.038	0.023	-9999	-10000	0	0
RPS6KB1	0.03	0.047	-9999	-10000	0	0
PARD6A	0.019	0	-9999	-10000	0	0
CBL	0.019	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0.004	-9999	-10000	0	0
PIK3R1	0.019	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.011	0.024	-9999	-10000	0	0
HRAS/GTP	-0.04	0.079	-9999	-0.3	4	4
Insulin Receptor	0.02	0.014	-9999	-0.24	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.037	0.038	-9999	-10000	0	0
PRKCI	0.009	0.017	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.017	0.034	-9999	-10000	0	0
SHC1	0.019	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0.035	0.016	-9999	-0.27	1	1
PI3K	0.031	0.035	-9999	-10000	0	0
NCK2	0.019	0	-9999	-10000	0	0
RHOQ	0.019	0	-9999	-10000	0	0
mol:H2O2	0	0.001	-9999	-10000	0	0
HRAS/GDP	0.014	0	-9999	-10000	0	0
AKT2	0.025	0.05	-9999	-10000	0	0
PRKCZ	0.006	0.042	-9999	-0.52	2	2
SH2B2	0.008	0.076	-9999	-0.54	7	7
SHC/SHIP	-0.019	0.11	-9999	-0.26	62	62
F2RL2	-0.061	0.18	-9999	-0.43	65	65
TRIP10	0.018	0.014	-9999	-0.24	1	1
Insulin Receptor/Insulin/Shc	0.027	0.006	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.025	0.008	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.048	0.006	-9999	-10000	0	0
RAPGEF1	0.019	0	-9999	-10000	0	0
RASA1	0.017	0.029	-9999	-0.54	1	1
NCK1	0.019	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	0.038	0.057	-9999	-0.28	11	11
TC10/GDP	0.014	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.039	0.012	-9999	-10000	0	0
INPP5D	-0.031	0.12	-9999	-0.28	62	62
SOS1	0.019	0	-9999	-10000	0	0
SGK1	0.002	0.003	-9999	-10000	0	0
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.019	0	-9999	-10000	0	0
IRS1	-0.003	0.072	-9999	-0.24	30	30
p62DOK/RasGAP	0.036	0.016	-9999	-0.27	1	1
INS	0.003	0.001	-9999	-10000	0	0
mol:PI-3-4-P2	-0.031	0.12	-9999	-0.28	62	62
GRB2	0.019	0	-9999	-10000	0	0
EIF4EBP1	0.03	0.047	-9999	-10000	0	0
PTPRA	0.021	0	-9999	-10000	0	0
PIK3CA	0.018	0.014	-9999	-0.24	1	1
TC10/GTP/CIP4	0.025	0.008	-9999	-10000	0	0
PDPK1	0.019	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.031	0.026	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.016	0.038	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS3	0.018	0.009	-9999	-10000	0	0
Par3/Par6	0.001	0.1	-9999	-0.27	41	41

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.019	0	-10000	0	-10000	0	0
mol:Halofuginone	0.005	0.013	-10000	0	-10000	0	0
ITGA1	0.009	0.05	-10000	0	-0.24	14	14
CDKN1A	0.031	0.025	-10000	0	-10000	0	0
PRL-3/alpha Tubulin	0.026	0.025	-10000	0	-0.38	1	1
mol:Ca2+	-0.075	0.14	-10000	0	-0.32	87	87
AGT	-0.089	0.2	-10000	0	-0.43	88	88
CCNA2	0.029	0.047	-10000	0	-10000	0	0
TUBA1B	0.019	0	-10000	0	-10000	0	0
EGR1	0.011	0.053	-10000	0	-0.32	1	1
CDK2/Cyclin E1	0.049	0.022	-10000	0	-10000	0	0
MAPK3	0.024	0.025	-10000	0	-0.38	1	1
PRL-2 /Rab GGTase beta	0.028	0	-10000	0	-10000	0	0
MAPK1	0.024	0.025	-10000	0	-0.38	1	1
PTP4A1	0.025	0.049	-10000	0	-0.35	1	1
PTP4A3	0.016	0.035	-10000	0	-0.34	3	3
PTP4A2	0.019	0	-10000	0	-10000	0	0
ITGB1	0.023	0.028	-10000	0	-0.38	1	1
SRC	0.019	0	-10000	0	-10000	0	0
RAC1	0.031	0.033	-10000	0	-0.38	1	1
Rab GGTase beta/Rab GGTase alpha	0.028	0	-10000	0	-10000	0	0
PRL-1/ATF-5	0.033	0.046	-10000	0	-10000	0	0
RABGGTA	0.019	0	-10000	0	-10000	0	0
BCAR1	0.002	0.023	0.38	1	-10000	0	1
RHOC	0.031	0.033	-10000	0	-0.38	1	1
RHOA	0.031	0.033	-10000	0	-0.38	1	1
cell motility	0.036	0.034	-10000	0	-0.38	1	1
PRL-1/alpha Tubulin	0.033	0.046	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	0.019	0.042	-10000	0	-0.38	1	1
ROCK1	0.036	0.034	-10000	0	-0.38	1	1
RABGGTB	0.019	0	-10000	0	-10000	0	0
CDK2	0.019	0	-10000	0	-10000	0	0
mitosis	0.025	0.048	-10000	0	-0.35	1	1
ATF5	0.019	0	-10000	0	-10000	0	0

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	-0.01	0.07	0.54	6	-10000	0	6
PI3K Class IB/PDE3B	0.01	0.07	-10000	0	-0.54	6	6
PDE3B	0.01	0.071	-10000	0	-0.54	6	6

×

Aurora B signaling

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
Condensin I complex	0.038	0.033	-9999	-0.27	3	3
STMN1	0.025	0.03	-9999	-0.38	2	2
Aurora B/RasGAP/Survivin	0.038	0.027	-9999	-0.32	2	2
Chromosomal passenger complex/Cul3 protein complex	0.019	0.054	-9999	-0.22	4	4
BIRC5	0.02	0.001	-9999	-10000	0	0
DES	-0.057	0.16	-9999	-0.56	32	32
Aurora C/Aurora B/INCENP	-0.032	0.13	-9999	-0.29	78	78
Aurora B/TACC1	0.025	0.018	-9999	-0.31	1	1
Aurora B/PP2A	0.028	0.021	-9999	-0.37	1	1
mol:GTP	0	0	-9999	-10000	0	0
CBX5	0.018	0.009	-9999	-0.15	1	1
mitotic metaphase/anaphase transition	0	0.001	-9999	-10000	0	0
NDC80	0.022	0.043	-9999	-0.38	4	4
Cul3 protein complex	-0.002	0.091	-9999	-0.34	16	16
KIF2C	0.03	0.011	-9999	-0.15	1	1
PEBP1	0.02	0.001	-9999	-10000	0	0
KIF20A	0.017	0.029	-9999	-0.54	1	1
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	0.027	0.03	-9999	-0.38	2	2
SEPT1	-0.15	0.25	-9999	-0.54	109	109
SMC2	0.017	0.029	-9999	-0.54	1	1
SMC4	0.019	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	0.041	0.038	-9999	-0.68	1	1
PSMA3	0.019	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0	0.001	-9999	-10000	0	0
H3F3B	0.02	0.018	-9999	-0.33	1	1
AURKB	0.019	0.029	-9999	-0.54	1	1
AURKC	-0.098	0.23	-9999	-0.54	77	77
CDCA8	0.02	0.001	-9999	-10000	0	0
cytokinesis	0.047	0.035	-9999	-0.36	2	2
Aurora B/Septin1	-0.019	0.13	-9999	-0.32	3	3
AURKA	0.019	0.001	-9999	-10000	0	0
INCENP	0.02	0.001	-9999	-10000	0	0
KLHL13	-0.039	0.13	-9999	-0.29	69	69
BUB1	0.019	0.001	-9999	-10000	0	0
hSgo1/Aurora B/Survivin	0.037	0.018	-9999	-0.28	1	1
EVI5	0.02	0.001	-9999	-10000	0	0
RhoA/GTP	0.057	0.025	-9999	-0.27	2	2
SGOL1	0.019	0	-9999	-10000	0	0
CENPA	0.033	0.037	-9999	-0.42	2	2
NCAPG	0.016	0.041	-9999	-0.54	2	2
Aurora B/HC8 Proteasome	0.028	0.021	-9999	-0.37	1	1
NCAPD2	0.019	0	-9999	-10000	0	0
Aurora B/PP1-gamma	0.027	0.03	-9999	-0.38	2	2
RHOA	0.019	0	-9999	-10000	0	0
NCAPH	0.017	0.029	-9999	-0.54	1	1
NPM1	0.026	0.029	-9999	-0.54	1	1
RASA1	0.017	0.029	-9999	-0.54	1	1
KLHL9	0.01	0.071	-9999	-0.54	6	6
mitotic prometaphase	0.001	0.001	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.028	0.021	-9999	-0.37	1	1
PPP1CC	0.017	0.029	-9999	-0.54	1	1
Centraspindlin	0.054	0.027	-9999	-0.3	2	2
RhoA/GDP	0.014	0	-9999	-10000	0	0
NSUN2	0.026	0.029	-9999	-0.54	1	1
MYLK	0.017	0.036	-9999	-0.33	4	4
KIF23	0.019	0.029	-9999	-0.54	1	1
VIM	0.026	0.021	-9999	-0.37	1	1
RACGAP1	0.02	0.001	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
NCL	0.026	0.029	-9999	-0.54	1	1
Chromosomal passenger complex	0.042	0.022	-9999	-0.34	1	1
Chromosomal passenger complex/EVI5	0.057	0.025	-9999	-0.27	1	1
TACC1	0.019	0	-9999	-10000	0	0
PPP2R5D	0.019	0	-9999	-10000	0	0
CUL3	0.019	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.022	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.085	0.042	-9999	-10000	0	0
ERC1	0.019	0	-9999	-10000	0	0
RIP2/NOD2	0.005	0.095	-9999	-0.38	21	21
NFKBIA	0.048	0	-9999	-10000	0	0
BIRC2	0.014	0.052	-9999	-0.46	4	4
IKBKB	0.019	0	-9999	-10000	0	0
RIPK2	0.019	0	-9999	-10000	0	0
IKBKG	0.037	0.062	-9999	-0.48	1	1
IKK complex/A20	0.007	0.14	-9999	-0.41	18	18
NEMO/A20/RIP2	0.019	0	-9999	-10000	0	0
XPO1	0.019	0	-9999	-10000	0	0
NEMO/ATM	0.046	0.06	-9999	-0.45	1	1
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.019	0	-9999	-10000	0	0
Exportin 1/RanGTP	0.026	0	-9999	-10000	0	0
IKK complex/ELKS	-0.009	0.039	-9999	-0.4	1	1
BCL10/MALT1/TRAF6	0.037	0.02	-9999	-0.32	1	1
NOD2	-0.013	0.13	-9999	-0.54	21	21
NFKB1	0.022	0	-9999	-10000	0	0
RELA	0.022	0	-9999	-10000	0	0
MALT1	0.017	0.029	-9999	-0.54	1	1
cIAP1/UbcH5C	0.024	0.038	-9999	-0.38	3	3
ATM	0.019	0	-9999	-10000	0	0
TNF/TNFR1A	-0.056	0.16	-9999	-0.38	75	75
TRAF6	0.019	0	-9999	-10000	0	0
PRKCA	0.013	0.044	-9999	-0.28	7	7
CHUK	0.019	0	-9999	-10000	0	0
UBE2D3	0.019	0	-9999	-10000	0	0
TNF	-0.095	0.22	-9999	-0.54	75	75
NF kappa B1 p50/RelA	0.052	0	-9999	-10000	0	0
BCL10	0.018	0.014	-9999	-0.24	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.047	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.022	0	-9999	-10000	0	0
TNFRSF1A	0.019	0	-9999	-10000	0	0
IKK complex	0.055	0.059	-9999	-0.44	1	1
CYLD	0.019	0	-9999	-10000	0	0
IKK complex/PKC alpha	0.059	0.061	-9999	-0.42	1	1

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.017	0.029	-10000	0	-0.54	1	1
HDAC2	0.019	0	-10000	0	-10000	0	0
GNB1/GNG2	0.024	0.073	-10000	0	-0.32	16	16
forebrain development	0.033	0.06	-10000	0	-0.38	4	4
GNAO1	-0.093	0.13	-10000	0	-0.24	156	156
SMO/beta Arrestin2	0.019	0.067	-10000	0	-0.38	10	10
SMO	0.005	0.091	-10000	0	-0.54	10	10
ARRB2	0.02	0.001	-10000	0	-10000	0	0
GLI3/SPOP	0.059	0.035	-10000	0	-10000	0	0
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
GSK3B	0.019	0	-10000	0	-10000	0	0
GNAI2	0.019	0.001	-10000	0	-10000	0	0
SIN3/HDAC complex	0.048	0.001	-10000	0	-10000	0	0
GNAI1	0.006	0.058	-10000	0	-0.24	19	19
XPO1	0.021	0.002	-10000	0	-10000	0	0
GLI1/Su(fu)	0.039	0.069	-10000	0	-0.37	3	3
SAP30	0.019	0	-10000	0	-10000	0	0
mol:GDP	0.005	0.091	-10000	0	-0.54	10	10
MIM/GLI2A	0.014	0.05	-10000	0	-0.54	3	3
IFT88	0.017	0.029	-10000	0	-0.54	1	1
GNAI3	0.019	0.001	-10000	0	-10000	0	0
GLI2	0.049	0.017	-10000	0	-10000	0	0
GLI3	0.051	0.037	0.2	8	-0.23	3	11
CSNK1D	0.019	0	-10000	0	-10000	0	0
CSNK1E	0.019	0	-10000	0	-10000	0	0
SAP18	0.019	0	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.017	0.029	-10000	0	-0.54	1	1
GNG2	0.01	0.071	-10000	0	-0.54	6	6
Gi family/GTP	-0.017	0.082	-10000	0	-0.31	13	13
SIN3B	0.019	0	-10000	0	-10000	0	0
SIN3A	0.019	0	-10000	0	-10000	0	0
GLI3/Su(fu)	0.071	0.026	-10000	0	-10000	0	0
GLI2/Su(fu)	0.064	0.034	-10000	0	-0.27	1	1
FOXA2	-0.006	0.066	-10000	0	-0.72	3	3
neural tube patterning	0.033	0.06	-10000	0	-0.38	4	4
SPOP	0.019	0	-10000	0	-10000	0	0
Su(fu)/PIAS1	0.037	0.033	-10000	0	-10000	0	0
GNB1	0.019	0	-10000	0	-10000	0	0
CSNK1G2	0.019	0	-10000	0	-10000	0	0
CSNK1G3	0.019	0	-10000	0	-10000	0	0
MTSS1	0.014	0.05	-10000	0	-0.54	3	3
embryonic limb morphogenesis	0.033	0.06	-10000	0	-0.38	4	4
SUFU	0.03	0.036	-10000	0	-10000	0	0
LGALS3	-0.005	0.11	-10000	0	-0.54	16	16
catabolic process	0.085	0.034	-10000	0	-10000	0	0
GLI3A/CBP	0.028	0.03	-10000	0	-0.34	2	2
KIF3A	0.019	0	-10000	0	-10000	0	0
GLI1	0.034	0.061	-10000	0	-0.39	4	4
RAB23	0.019	0	-10000	0	-10000	0	0
CSNK1A1	0.019	0	-10000	0	-10000	0	0
IFT172	0.013	0.058	-10000	0	-0.54	4	4
RBBP7	0.019	0	-10000	0	-10000	0	0
Su(fu)/Galectin3	0.023	0.071	-10000	0	-0.27	16	16
GNAZ	-0.015	0.094	-10000	0	-0.26	46	46
RBBP4	0.019	0	-10000	0	-10000	0	0
CSNK1G1	0.019	0	-10000	0	-10000	0	0
PIAS1	0.019	0	-10000	0	-10000	0	0
PRKACA	0.019	0	-10000	0	-10000	0	0
GLI2/SPOP	0.055	0.017	-10000	0	-10000	0	0
STK36	0.021	0.002	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.007	0.081	-10000	0	-0.32	12	12
PTCH1	0.037	0.099	-10000	0	-1.1	2	2
MIM/GLI1	0.041	0.063	-10000	0	-0.37	4	4
CREBBP	0.028	0.029	-10000	0	-0.34	2	2
Su(fu)/SIN3/HDAC complex	0.055	0.019	-10000	0	-0.26	1	1

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.003	0.076	-9999	-0.31	18	18
HRAS	0.019	0	-9999	-10000	0	0
EGFR	-0.007	0.086	-9999	-0.27	32	32
AKT	0.039	0.026	-9999	-10000	0	0
FOXO3	0.019	0	-9999	-10000	0	0
AKT1	0.019	0	-9999	-10000	0	0
FOXO1	0.019	0	-9999	-10000	0	0
AKT3	0.019	0	-9999	-10000	0	0
FOXO4	0.019	0	-9999	-10000	0	0
MET	-0.024	0.14	-9999	-0.43	35	35
PIK3CA	0.018	0.014	-9999	-0.24	1	1
PIK3CB	0.019	0	-9999	-10000	0	0
NRAS	0.019	0	-9999	-10000	0	0
PIK3CG	-0.056	0.19	-9999	-0.54	49	49
PIK3R3	0.019	0	-9999	-10000	0	0
PIK3R2	0.019	0	-9999	-10000	0	0
NF1	0.019	0	-9999	-10000	0	0
RAS	0.009	0.049	-9999	-10000	0	0
ERBB2	0.019	0	-9999	-10000	0	0
proliferation/survival/translation	-0.03	0.039	-9999	-10000	0	0
PI3K	0.008	0.063	-9999	-0.23	8	8
PIK3R1	0.019	0	-9999	-10000	0	0
KRAS	0.018	0.014	-9999	-0.24	1	1
FOXO	0.05	0.029	-9999	-10000	0	0
AKT2	0.019	0	-9999	-10000	0	0
PTEN	0.017	0.029	-9999	-0.54	1	1

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	0.28	0.18	-9999	-0.98	2	2
PLK1	0.09	0.036	-9999	-10000	0	0
BIRC5	0.09	0.036	-9999	-10000	0	0
HSPA1B	0.27	0.19	-9999	-0.98	2	2
MAP2K1	0.065	0.026	-9999	-10000	0	0
BRCA2	0.27	0.23	-9999	-1.1	6	6
FOXM1	0.29	0.2	-9999	-1.2	2	2
XRCC1	0.28	0.18	-9999	-0.98	2	2
FOXM1B/p19	-0.022	0.1	-9999	-1	2	2
Cyclin D1/CDK4	0.22	0.2	-9999	-0.89	2	2
CDC2	0.28	0.19	-9999	-1	2	2
TGFA	0.21	0.23	-9999	-0.81	5	5
SKP2	0.28	0.18	-9999	-0.98	2	2
CCNE1	0.028	0.006	-9999	-10000	0	0
CKS1B	0.28	0.18	-9999	-0.98	2	2
RB1	-0.004	0.081	-9999	-0.96	2	2
FOXM1C/SP1	0.27	0.18	-9999	-1.1	2	2
AURKB	0.086	0.09	-9999	-1.5	1	1
CENPF	0.28	0.19	-9999	-1.2	2	2
CDK4	0.032	0.023	-9999	-0.24	2	2
MYC	0.27	0.17	-9999	-0.85	2	2
CHEK2	0.065	0.026	-9999	-10000	0	0
ONECUT1	0.18	0.24	-9999	-0.94	2	2
CDKN2A	-0.11	0.14	-9999	-0.26	171	171
LAMA4	0.27	0.19	-9999	-0.98	2	2
FOXM1B/HNF6	0.18	0.24	-9999	-1.1	2	2
FOS	0.27	0.19	-9999	-0.98	2	2
SP1	0.021	0.002	-9999	-10000	0	0
CDC25B	0.28	0.18	-9999	-0.98	2	2
response to radiation	0.039	0.024	-9999	-10000	0	0
CENPB	0.28	0.18	-9999	-0.98	2	2
CENPA	0.28	0.2	-9999	-1.4	2	2
NEK2	0.27	0.21	-9999	-1.3	3	3
HIST1H2BA	0.27	0.18	-9999	-0.99	2	2
CCNA2	0.027	0.031	-9999	-0.55	1	1
EP300	0.019	0	-9999	-10000	0	0
CCNB1/CDK1	0.28	0.19	-9999	-1.1	2	2
CCNB2	0.27	0.22	-9999	-0.96	6	6
CCNB1	0.28	0.19	-9999	-1	2	2
ETV5	0.28	0.2	-9999	-1.1	3	3
ESR1	0.26	0.25	-9999	-1	9	9
CCND1	0.22	0.21	-9999	-0.9	2	2
GSK3A	0.057	0.024	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	0.079	0.035	-9999	-0.35	1	1
CDK2	0.028	0.006	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.048	0.026	-9999	-10000	0	0
FOXM1B/Cbp/p300	0.1	0.16	-9999	-1.1	2	2
GAS1	0.27	0.22	-9999	-1	5	5
MMP2	0.26	0.22	-9999	-0.99	4	4
RB1/FOXM1C	0.24	0.2	-9999	-0.93	3	3
CREBBP	0.019	0	-9999	-10000	0	0

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.004	0.076	-9999	-0.31	18	18
PDGF/PDGFRA/CRKL	0.017	0.053	-9999	-0.37	4	4
positive regulation of JUN kinase activity	0.039	0.041	-9999	-0.26	4	4
CRKL	0.018	0.014	-9999	-0.24	1	1
PDGF/PDGFRA/Caveolin-3	0.004	0.052	-9999	-0.38	4	4
AP1	0.02	0.074	-9999	-0.44	1	1
mol:IP3	0.017	0.055	-9999	-0.34	5	5
PLCG1	0.017	0.055	-9999	-0.34	5	5
PDGF/PDGFRA/alphaV Integrin	0.017	0.053	-9999	-0.37	4	4
RAPGEF1	0.019	0	-9999	-10000	0	0
CRK	0.019	0	-9999	-10000	0	0
mol:Ca2+	0.017	0.055	-9999	-0.34	5	5
CAV3	0	0	-9999	-10000	0	0
CAV1	0.019	0	-9999	-10000	0	0
SHC/Grb2/SOS1	0.041	0.041	-9999	-0.27	4	4
PDGF/PDGFRA/Shf	0.017	0.054	-9999	-0.37	4	4
FOS	0.02	0.074	-9999	-0.39	2	2
JUN	-0.013	0.053	-9999	-0.17	36	36
oligodendrocyte development	0.017	0.053	-9999	-0.37	4	4
GRB2	0.019	0	-9999	-10000	0	0
PIK3R1	0.019	0	-9999	-10000	0	0
mol:DAG	0.017	0.055	-9999	-0.34	5	5
PDGF/PDGFRA	0.004	0.076	-9999	-0.31	18	18
actin cytoskeleton reorganization	0.008	0.073	-9999	-0.38	8	8
SRF	0.024	0.003	-9999	-10000	0	0
SHC1	0.019	0	-9999	-10000	0	0
PI3K	0.029	0.045	-9999	-0.3	4	4
PDGF/PDGFRA/Crk/C3G	0.03	0.045	-9999	-0.3	4	4
JAK1	0.016	0.052	-9999	-0.37	4	4
ELK1/SRF	0.034	0.039	-9999	-0.27	4	4
SHB	0.006	0.071	-9999	-0.33	14	14
SHF	0.017	0.019	-9999	-0.24	2	2
CSNK2A1	0.015	0.007	-9999	-10000	0	0
GO:0007205	0.016	0.056	-9999	-0.41	4	4
SOS1	0.019	0	-9999	-10000	0	0
Ras protein signal transduction	0.039	0.041	-9999	-0.26	4	4
PDGF/PDGFRA/SHB	0.008	0.073	-9999	-0.38	8	8
PDGF/PDGFRA/Caveolin-1	0.018	0.053	-9999	-0.37	4	4
ITGAV	0.018	0.014	-9999	-0.24	1	1
ELK1	0.022	0.049	-9999	-0.34	4	4
PIK3CA	0.018	0.014	-9999	-0.24	1	1
PDGF/PDGFRA/Crk	0.018	0.053	-9999	-0.37	4	4
JAK-STAT cascade	0.016	0.052	-9999	-0.37	4	4
cell proliferation	0.017	0.054	-9999	-0.37	4	4

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.019	0	-10000	0	-10000	0	0
HDAC4	0.019	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	0.066	0.38	10	-10000	0	10
CDKN1A	0.008	0.018	-10000	0	-0.2	3	3
KAT2B	0.016	0.041	-10000	0	-0.54	2	2
BAX	0.019	0	-10000	0	-10000	0	0
FOXO3	-0.007	0.001	-10000	0	-10000	0	0
FOXO1	0.019	0	-10000	0	-10000	0	0
FOXO4	0.026	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.019	0	-10000	0	-10000	0	0
TAT	0	0	-10000	0	-10000	0	0
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.015	0.041	-10000	0	-0.45	2	2
PPARGC1A	-0.094	0.15	-10000	0	-0.26	146	146
FHL2	0.01	0.071	-10000	0	-0.54	6	6
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.024	0.004	-10000	0	-10000	0	0
HIST2H4A	0.011	0.066	-10000	0	-0.38	10	10
SIRT1/FOXO3a	0.003	0.004	-10000	0	-10000	0	0
SIRT1	0.013	0.006	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.035	0.004	-10000	0	-10000	0	0
SIRT1/Histone H1b	0.028	0.005	-10000	0	-10000	0	0
apoptosis	-0.034	0.004	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.042	0.085	-10000	0	-0.32	10	10
p53/SIRT1	0.001	0.016	-10000	0	-10000	0	0
SIRT1/FOXO4	0.029	0.004	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	0.028	0.041	-10000	0	-0.29	6	6
HIST1H1E	0.026	0.002	-10000	0	-10000	0	0
SIRT1/p300	0.024	0.004	-10000	0	-10000	0	0
muscle cell differentiation	-0.023	0.035	0.38	2	-10000	0	2
TP53	0.013	0.006	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0.035	0.004	-10000	0	-10000	0	0
CREBBP	0.019	0	-10000	0	-10000	0	0
MEF2D	0.019	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.01	0.004	-10000	0	-10000	0	0
ACSS2	0.021	0.019	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	0.023	0.035	-10000	0	-0.38	2	2

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	0.05	0.038	0.22	1	-0.31	2	3
CaM/Ca2+	0.014	0	-10000	0	-10000	0	0
AKT1	0.019	0	-10000	0	-10000	0	0
AKT2	0.019	0	-10000	0	-10000	0	0
STXBP4	0.019	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.048	0.046	0.23	1	-0.35	2	3
YWHAZ	0.019	0	-10000	0	-10000	0	0
CALM1	0.019	0	-10000	0	-10000	0	0
YWHAQ	0.019	0	-10000	0	-10000	0	0
TBC1D4	0.023	0.028	-10000	0	-0.38	1	1
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.019	0	-10000	0	-10000	0	0
YWHAB	0.019	0	-10000	0	-10000	0	0
SNARE/Synip	0.038	0	-10000	0	-10000	0	0
YWHAG	0.019	0	-10000	0	-10000	0	0
ASIP	-0.007	0.072	-10000	0	-0.24	31	31
PRKCI	0.019	0	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0.014	0	-10000	0	-10000	0	0
RHOQ	0.019	0	-10000	0	-10000	0	0
GYS1	0.034	0	-10000	0	-10000	0	0
PRKCZ	0.016	0.041	-10000	0	-0.54	2	2
TRIP10	0.018	0.014	-10000	0	-0.24	1	1
TC10/GTP/CIP4/Exocyst	0.025	0.008	-10000	0	-10000	0	0
AS160/14-3-3	0.036	0.032	-10000	0	-10000	0	0
VAMP2	0.019	0	-10000	0	-10000	0	0
SLC2A4	0.049	0.048	0.23	1	-0.38	2	3
STX4	0.019	0	-10000	0	-10000	0	0
GSK3B	0.031	0	-10000	0	-10000	0	0
SFN	-0.034	0.1	-10000	0	-0.24	73	73
LNPEP	0.019	0	-10000	0	-10000	0	0
YWHAE	0.019	0	-10000	0	-10000	0	0

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.031	0.009	-9999	-10000	0	0
PLK1	0.058	0.14	-9999	-10000	0	0
CDKN1B	0.18	0.024	-9999	-10000	0	0
FOXO3	0.053	0.15	-9999	-0.38	1	1
KAT2B	0.019	0.044	-9999	-0.52	2	2
FOXO1/SIRT1	0.057	0.024	-9999	-10000	0	0
CAT	0.058	0.14	-9999	-10000	0	0
CTNNB1	0.019	0	-9999	-10000	0	0
AKT1	0.025	0.019	-9999	-10000	0	0
FOXO1	0.035	0.011	-9999	-10000	0	0
MAPK10	0.019	0.05	-9999	-10000	0	0
mol:GTP	0.003	0	-9999	-10000	0	0
FOXO4	0.1	0.03	-9999	-10000	0	0
response to oxidative stress	0.007	0.02	-9999	-10000	0	0
FOXO3A/SIRT1	0.15	0.042	-9999	-10000	0	0
XPO1	0.02	0	-9999	-10000	0	0
EP300	0.02	0	-9999	-10000	0	0
BCL2L11	0.018	0.088	-9999	-1.4	1	1
FOXO1/SKP2	0.042	0.009	-9999	-10000	0	0
mol:GDP	0.007	0.02	-9999	-10000	0	0
RAN	0.021	0	-9999	-10000	0	0
GADD45A	0.14	0.031	-9999	-10000	0	0
YWHAQ	0.019	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.074	0.023	-9999	-10000	0	0
MST1	0.019	0.041	-9999	-0.36	3	3
CSNK1D	0.019	0	-9999	-10000	0	0
CSNK1E	0.019	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.052	0.034	-9999	-10000	0	0
YWHAB	0.019	0	-9999	-10000	0	0
MAPK8	0.044	0.009	-9999	-10000	0	0
MAPK9	0.043	0.009	-9999	-10000	0	0
YWHAG	0.019	0	-9999	-10000	0	0
YWHAE	0.019	0	-9999	-10000	0	0
YWHAZ	0.019	0	-9999	-10000	0	0
SIRT1	0.037	0.034	-9999	-10000	0	0
SOD2	0.15	0.051	-9999	-10000	0	0
RBL2	0.079	0.11	-9999	-10000	0	0
RAL/GDP	0.037	0.014	-9999	-10000	0	0
CHUK	0.022	0.019	-9999	-10000	0	0
Ran/GTP	0.019	0.001	-9999	-10000	0	0
CSNK1G2	0.019	0	-9999	-10000	0	0
RAL/GTP	0.045	0.014	-9999	-10000	0	0
CSNK1G1	0.019	0	-9999	-10000	0	0
FASLG	-0.43	0.69	-9999	-1.4	120	120
SKP2	0.019	0	-9999	-10000	0	0
USP7	0.021	0	-9999	-10000	0	0
IKBKB	0.022	0.019	-9999	-10000	0	0
CCNB1	0.058	0.14	-9999	-10000	0	0
FOXO1-3a-4/beta catenin	0.12	0.11	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.042	0.009	-9999	-10000	0	0
CSNK1A1	0.019	0	-9999	-10000	0	0
SGK1	0.022	0.019	-9999	-10000	0	0
CSNK1G3	0.019	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.034	0.001	-9999	-10000	0	0
ZFAND5	0.1	0.028	-9999	-10000	0	0
SFN	-0.034	0.1	-9999	-0.24	73	73
CDK2	0.018	0	-9999	-10000	0	0
FOXO3A/14-3-3	0.056	0.046	-9999	-10000	0	0
CREBBP	0.018	0	-9999	-10000	0	0
FBXO32	0.056	0.15	-9999	-1.2	1	1
BCL6	0.079	0.11	-9999	-10000	0	0
RALB	0.02	0	-9999	-10000	0	0
RALA	0.02	0	-9999	-10000	0	0
YWHAH	0.019	0	-9999	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.017	0.029	-10000	0	-0.54	1	1
HDAC3	0.019	0	-10000	0	-10000	0	0
VDR	0.016	0.041	-10000	0	-0.54	2	2
Cbp/p300/PCAF	0.036	0.026	-10000	0	-0.32	2	2
EP300	0.019	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.044	0.043	-10000	0	-0.22	1	1
KAT2B	0.016	0.041	-10000	0	-0.54	2	2
MAPK14	0.019	0	-10000	0	-10000	0	0
AKT1	0.025	0.059	0.22	7	-0.24	13	20
RAR alpha/9cRA/Cyclin H	0.057	0.022	-10000	0	-0.26	1	1
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.04	0.049	-10000	0	-0.18	16	16
CDC2	0.001	0	-10000	0	-10000	0	0
response to UV	0.001	0	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.028	0.017	-10000	0	-10000	0	0
NCOR2	0.019	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.012	0.03	-10000	0	-0.39	2	2
RXRs/RARs/NRIP1/9cRA	0.035	0.072	-10000	0	-0.58	1	1
NCOA2	0.018	0.014	-10000	0	-0.24	1	1
NCOA3	0.019	0	-10000	0	-10000	0	0
NCOA1	0.019	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.016	0.041	-10000	0	-0.54	2	2
RARG	0.02	0	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.026	0	-10000	0	-10000	0	0
MAPK3	0.02	0	-10000	0	-10000	0	0
MAPK1	0.019	0	-10000	0	-10000	0	0
MAPK8	0.02	0.001	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.029	0.063	-10000	0	-0.63	1	1
RARA	0.03	0.021	-10000	0	-0.23	1	1
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.04	0.049	-10000	0	-0.25	1	1
PRKCA	0.017	0.044	-10000	0	-0.28	7	7
RXRs/RARs/NRIP1/9cRA/HDAC1	0.026	0.076	-10000	0	-0.35	5	5
RXRG	-0.05	0.15	-10000	0	-0.32	83	83
RXRA	0.037	0.021	-10000	0	-0.23	1	1
RXRB	0.028	0.028	-10000	0	-0.26	2	2
VDR/Vit D3/DNA	0.012	0.03	-10000	0	-0.39	2	2
RBP1	0	0.09	-10000	0	-0.38	17	17
CRBP1/9-cic-RA	0.001	0.065	-10000	0	-0.27	17	17
RARB	0	0.11	-10000	0	-0.52	15	15
PRKCG	0.014	0.025	-10000	0	-0.24	3	3
MNAT1	0.019	0	-10000	0	-10000	0	0
RAR alpha/RXRs	0.033	0.074	-10000	0	-0.63	1	1
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.038	0.065	-10000	0	-0.31	4	4
proteasomal ubiquitin-dependent protein catabolic process	0.046	0.043	-10000	0	-0.21	1	1
RXRs/RARs/NRIP1/9cRA/HDAC3	0.026	0.076	-10000	0	-0.35	5	5
positive regulation of DNA binding	-0.001	0.015	-10000	0	-0.25	1	1
NRIP1	0.027	0.072	-10000	0	-0.56	1	1
RXRs/RARs	0.019	0.077	-10000	0	-0.36	5	5
RXRs/RXRs/DNA/9cRA	0.021	0.06	-10000	0	-0.66	1	1
PRKACA	0.019	0	-10000	0	-10000	0	0
CDK7	0.019	0	-10000	0	-10000	0	0
TFIIH	0.038	0	-10000	0	-10000	0	0
RAR alpha/9cRA	0.052	0.014	-10000	0	-10000	0	0
CCNH	0.019	0	-10000	0	-10000	0	0
CREBBP	0.019	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	0	0	-10000	0	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	-0.009	0.1	-9999	-0.38	20	20
AKT1	0.077	0.052	-9999	-10000	0	0
PTK2B	0.02	0.087	-9999	-0.33	1	1
VEGFR2 homodimer/Frs2	0.039	0.034	-9999	-10000	0	0
CAV1	0.019	0	-9999	-10000	0	0
CALM1	0.019	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.044	0.046	-9999	-10000	0	0
endothelial cell proliferation	0.009	0.13	-9999	-0.36	4	4
mol:Ca2+	0.049	0.041	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.055	0.043	-9999	-10000	0	0
RP11-342D11.1	0.038	0.04	-9999	-10000	0	0
CDH5	0.018	0.014	-9999	-0.24	1	1
VEGFA homodimer	0.042	0.033	-9999	-10000	0	0
SHC1	0.019	0	-9999	-10000	0	0
SHC2	-0.062	0.12	-9999	-0.25	111	111
HRAS/GDP	-0.004	0.018	-9999	-10000	0	0
SH2D2A	-0.028	0.16	-9999	-0.54	31	31
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.02	0.12	-9999	-0.52	1	1
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.018	0.1	-9999	-0.38	3	3
VEGFR1 homodimer	0.018	0.014	-9999	-0.24	1	1
SHC/GRB2/SOS1	0.064	0.04	-9999	-10000	0	0
GRB10	0.049	0.044	-9999	-10000	0	0
PTPN11	0.019	0	-9999	-10000	0	0
GRB2	0.019	0	-9999	-10000	0	0
PAK1	0.018	0.014	-9999	-0.24	1	1
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.062	0.042	-9999	-10000	0	0
HRAS	0.019	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	0.033	0.06	-9999	-10000	0	0
HIF1A	0.019	0	-9999	-10000	0	0
FRS2	0.017	0.024	-9999	-0.24	3	3
oxygen and reactive oxygen species metabolic process	0.053	0.042	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.014	0.036	-9999	-0.24	7	7
Nck/Pak	0.028	0.009	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.046	0.044	-9999	-10000	0	0
mol:GDP	-0.005	0.02	-9999	-10000	0	0
mol:NADP	0.071	0.042	-9999	-0.33	1	1
eNOS/Hsp90	0.076	0.043	-9999	-0.31	1	1
PIK3R1	0.019	0	-9999	-10000	0	0
mol:IP3	0.049	0.041	-9999	-10000	0	0
HIF1A/ARNT	0.028	0	-9999	-10000	0	0
SHB	0.006	0.071	-9999	-0.33	14	14
VEGFA	0.006	0.061	-9999	-0.24	21	21
VEGFC	0.018	0.014	-9999	-0.24	1	1
FAK1/Vinculin	0.049	0.071	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.019	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.028	0.087	-9999	-10000	0	0
PTPN6	-0.12	0.24	-9999	-0.54	92	92
EPAS1	0.028	0.022	-9999	-10000	0	0
mol:L-citrulline	0.071	0.042	-9999	-0.33	1	1
ITGAV	0.018	0.014	-9999	-0.24	1	1
PIK3CA	0.018	0.014	-9999	-0.24	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.054	0.044	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer	0.052	0.047	-9999	-10000	0	0
VEGFR2/3 heterodimer	0.038	0.039	-9999	-0.32	1	1
VEGFB	0.019	0	-9999	-10000	0	0
MAPK11	0.05	0.041	-9999	-10000	0	0
VEGFR2 homodimer	0.036	0.038	-9999	-10000	0	0
FLT1	0.018	0.014	-9999	-0.24	1	1
NEDD4	0.02	0.019	-9999	-0.24	2	2
MAPK3	0.014	0.073	-9999	-10000	0	0
MAPK1	0.014	0.073	-9999	-10000	0	0
VEGFA145/NRP2	0.019	0.046	-9999	-0.38	1	1
VEGFR1/2 heterodimer	0.04	0.035	-9999	-0.32	1	1
KDR	0.036	0.038	-9999	-10000	0	0
VEGFA165/NRP1/VEGFR2 homodimer	0.056	0.045	-9999	-10000	0	0
SRC	0.019	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.018	0.07	-9999	-10000	0	0
PI3K	0.069	0.057	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.046	0.044	-9999	-10000	0	0
FES	0.043	0.059	-9999	-10000	0	0
GAB1	0.064	0.04	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src	0.046	0.044	-9999	-10000	0	0
CTNNB1	0.019	0	-9999	-10000	0	0
SOS1	0.019	0	-9999	-10000	0	0
ARNT	0.019	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.077	0.041	-9999	-0.31	1	1
VEGFR2 homodimer/VEGFA homodimer/Yes	0.046	0.044	-9999	-10000	0	0
PI3K/GAB1	0.082	0.053	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.06	0.043	-9999	-10000	0	0
PRKACA	0.019	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.047	0.037	-9999	-0.28	1	1
HSP90AA1	0.017	0.029	-9999	-0.54	1	1
CDC42	0.05	0.042	-9999	-10000	0	0
actin cytoskeleton reorganization	0.018	0.099	-9999	-0.38	3	3
PTK2	0.041	0.073	-9999	-10000	0	0
EDG1	0.038	0.04	-9999	-10000	0	0
mol:DAG	0.049	0.041	-9999	-10000	0	0
CaM/Ca2+	0.055	0.039	-9999	-10000	0	0
MAP2K3	0.052	0.042	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.059	0.048	-9999	-10000	0	0
PLCG1	0.05	0.042	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.048	0.056	-9999	-10000	0	0
IQGAP1	0.019	0	-9999	-10000	0	0
YES1	0.019	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.046	0.044	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.035	0.15	-9999	-0.38	12	12
cell migration	0.073	0.064	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.067	0.055	-9999	-10000	0	0
FYN	0.019	0	-9999	-10000	0	0
VEGFB/NRP1	0.047	0.039	-9999	-10000	0	0
mol:NO	0.071	0.042	-9999	-0.33	1	1
PXN	0.019	0	-9999	-10000	0	0
HRAS/GTP	-0.004	0.018	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.056	0.047	-9999	-10000	0	0
VHL	0.019	0	-9999	-10000	0	0
ITGB3	-0.033	0.14	-9999	-0.35	51	51
NOS3	0.073	0.044	-9999	-0.37	1	1
VEGFR2 homodimer/VEGFA homodimer/Sck	0.003	0.079	-9999	-10000	0	0
RAC1	0.019	0	-9999	-10000	0	0
PRKCA	0.05	0.048	-9999	-0.33	1	1
PRKCB	-0.033	0.14	-9999	-0.34	16	16
VCL	0.019	0	-9999	-10000	0	0
VEGFA165/NRP1	0.043	0.042	-9999	-10000	0	0
VEGFR1/2 heterodimer/VEGFA homodimer	0.045	0.047	-9999	-0.39	1	1
VEGFA165/NRP2	0.019	0.046	-9999	-0.38	1	1
MAPKKK cascade	0.075	0.04	-9999	-10000	0	0
NRP2	0.017	0.029	-9999	-0.54	1	1
VEGFC homodimer	0.018	0.014	-9999	-0.24	1	1
NCK1	0.019	0	-9999	-10000	0	0
ROCK1	0.019	0	-9999	-10000	0	0
FAK1/Paxillin	0.049	0.071	-9999	-10000	0	0
MAP3K13	0.049	0.045	-9999	-10000	0	0
PDPK1	0.068	0.051	-9999	-10000	0	0

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.017	0.022	-9999	-0.28	2	2
TRAF2/ASK1	0.024	0.026	-9999	-0.32	2	2
ATM	0.019	0	-9999	-10000	0	0
MAP2K3	0.042	0.02	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.042	0.05	-9999	-0.44	2	2
hyperosmotic response	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
GADD45G	-0.046	0.18	-9999	-0.53	43	43
TXN	0.01	0	-9999	-10000	0	0
CALM1	0.019	0	-9999	-10000	0	0
GADD45A	0.017	0.024	-9999	-0.24	3	3
GADD45B	0.019	0	-9999	-10000	0	0
MAP3K1	0.019	0	-9999	-10000	0	0
MAP3K6	0.018	0.014	-9999	-0.24	1	1
MAP3K7	0.019	0	-9999	-10000	0	0
MAP3K4	0.019	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
ASK1/ASK2	0.025	0.032	-9999	-0.38	2	2
TAK1/TAB family	-0.002	0	-9999	-10000	0	0
RAC1/OSM/MEKK3	0.036	0	-9999	-10000	0	0
TRAF2	0.019	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.001	0.011	-9999	-10000	0	0
TRAF6	0.01	0	-9999	-10000	0	0
RAC1	0.019	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
CAMK2B	-0.011	0.1	-9999	-0.33	31	31
CCM2	0.019	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB	0.008	0.064	-9999	-0.32	9	9
MAPK11	0.019	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.018	0.063	-9999	-0.29	11	11
OSM/MEKK3	0.028	0	-9999	-10000	0	0
TAOK1	0.02	0	-9999	-10000	0	0
TAOK2	0.02	0	-9999	-10000	0	0
TAOK3	0.02	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.019	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
MAP3K5	0.016	0.041	-9999	-0.54	2	2
MAP3K10	0.019	0	-9999	-10000	0	0
MAP3K3	0.019	0	-9999	-10000	0	0
TRX/ASK1	0.02	0.025	-9999	-0.32	2	2
GADD45/MTK1/MTK1	0.008	0.099	-9999	-0.26	42	42

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.043	0.042	-9999	-0.28	6	6
HDAC3	0.019	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC4	0.014	0	-9999	-10000	0	0
GATA1/HDAC5	0.014	0	-9999	-10000	0	0
GATA2/HDAC5	0.025	0.025	-9999	-0.15	7	7
HDAC5/BCL6/BCoR	0.038	0	-9999	-10000	0	0
HDAC9	-0.008	0.12	-9999	-0.54	18	18
Glucocorticoid receptor/Hsp90/HDAC6	0.037	0.019	-9999	-0.32	1	1
HDAC4/ANKRA2	0.027	0.021	-9999	-0.38	1	1
HDAC5/YWHAB	0.028	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.025	0	-9999	-10000	0	0
GATA2	0.014	0.036	-9999	-0.24	7	7
HDAC4/RFXANK	0.028	0	-9999	-10000	0	0
BCOR	0.019	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.019	0	-9999	-10000	0	0
HDAC5	0.019	0	-9999	-10000	0	0
GNB1/GNG2	0.021	0.052	-9999	-0.38	6	6
Histones	0.036	0.051	-9999	-10000	0	0
ADRBK1	0.019	0	-9999	-10000	0	0
HDAC4	0.019	0	-9999	-10000	0	0
XPO1	0.019	0	-9999	-10000	0	0
HDAC5/ANKRA2	0.027	0.021	-9999	-0.38	1	1
HDAC4/Ubc9	0.028	0	-9999	-10000	0	0
HDAC7	0.019	0	-9999	-10000	0	0
HDAC5/14-3-3 E	0.028	0	-9999	-10000	0	0
TUBA1B	0.019	0	-9999	-10000	0	0
HDAC6	0.019	0	-9999	-10000	0	0
HDAC5/RFXANK	0.028	0	-9999	-10000	0	0
CAMK4	-0.063	0.2	-9999	-0.54	54	54
Tubulin/HDAC6	0.038	0	-9999	-10000	0	0
SUMO1	0.019	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.019	0	-9999	-10000	0	0
GATA1	0	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.019	0	-9999	-10000	0	0
NR3C1	0.019	0	-9999	-10000	0	0
SUMO1/HDAC4	0.04	0	-9999	-10000	0	0
SRF	0.019	0	-9999	-10000	0	0
HDAC4/YWHAB	0.028	0	-9999	-10000	0	0
Tubulin	0.028	0	-9999	-10000	0	0
HDAC4/14-3-3 E	0.028	0	-9999	-10000	0	0
GNB1	0.019	0	-9999	-10000	0	0
RANGAP1	0.019	0	-9999	-10000	0	0
BCL6/BCoR	0.028	0	-9999	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0.038	0	-9999	-10000	0	0
HDAC4/SRF	-0.014	0.13	-9999	-0.32	54	54
HDAC4/ER alpha	0.02	0.056	-9999	-0.38	7	7
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.036	0.05	-9999	-10000	0	0
cell motility	0.038	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.019	0	-9999	-10000	0	0
HDAC7/HDAC3	0.028	0	-9999	-10000	0	0
BCL6	0.019	0	-9999	-10000	0	0
HDAC4/CaMK II delta B	0.019	0	-9999	-10000	0	0
Hsp90/HDAC6	0.027	0.021	-9999	-0.38	1	1
ESR1	0.008	0.076	-9999	-0.54	7	7
HDAC6/HDAC11	0.028	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.043	0	-9999	-10000	0	0
NPC	0.011	0	-9999	-10000	0	0
MEF2C	0.016	0.041	-9999	-0.54	2	2
RAN	0.019	0	-9999	-10000	0	0
HDAC4/MEF2C	0.054	0.023	-9999	-0.26	2	2
GNG2	0.01	0.071	-9999	-0.54	6	6
NCOR2	0.019	0	-9999	-10000	0	0
TUBB2A	0.019	0	-9999	-10000	0	0
HDAC11	0.019	0	-9999	-10000	0	0
HSP90AA1	0.017	0.029	-9999	-0.54	1	1
RANBP2	0.019	0	-9999	-10000	0	0
ANKRA2	0.017	0.029	-9999	-0.54	1	1
RFXANK	0.019	0	-9999	-10000	0	0
nuclear import	-0.037	0	-9999	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.038	0.07	-10000	0	-1.1	1	1
regulation of axonogenesis	-0.031	0.013	-10000	0	-10000	0	0
myoblast fusion	-0.025	0.035	0.41	1	-10000	0	1
mol:GTP	0.013	0.019	-10000	0	-0.23	1	1
regulation of calcium-dependent cell-cell adhesion	-0.024	0.084	0.29	23	-10000	0	23
ARF1/GTP	0.025	0.015	-10000	0	-10000	0	0
mol:GM1	0.011	0.014	-10000	0	-0.17	1	1
mol:Choline	0.03	0.012	-10000	0	-10000	0	0
lamellipodium assembly	0.029	0.037	-10000	0	-0.44	1	1
MAPK3	0.031	0.028	-10000	0	-0.33	1	1
ARF6/GTP/NME1/Tiam1	0.025	0.084	-10000	0	-0.29	23	23
ARF1	0.019	0	-10000	0	-10000	0	0
ARF6/GDP	0.025	0.035	-10000	0	-0.41	1	1
ARF1/GDP	0.034	0.033	-10000	0	-0.37	1	1
ARF6	0.018	0.011	-10000	0	-10000	0	0
RAB11A	0.019	0	-10000	0	-10000	0	0
TIAM1	-0.013	0.13	-10000	0	-0.54	22	22
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.031	0.028	-10000	0	-0.33	1	1
actin filament bundle formation	-0.028	0.03	0.37	1	-10000	0	1
KALRN	0	0.037	-10000	0	-0.3	3	3
RAB11FIP3/RAB11A	0.028	0	-10000	0	-10000	0	0
RhoA/GDP	0.029	0.031	-10000	0	-0.38	1	1
NME1	0.02	0.002	-10000	0	-10000	0	0
Rac1/GDP	0.029	0.031	-10000	0	-0.38	1	1
substrate adhesion-dependent cell spreading	0.013	0.019	-10000	0	-0.23	1	1
cortical actin cytoskeleton organization	0.029	0.038	-10000	0	-0.45	1	1
RAC1	0.019	0	-10000	0	-10000	0	0
liver development	0.013	0.019	-10000	0	-0.23	1	1
ARF6/GTP	0.013	0.019	-10000	0	-0.23	1	1
RhoA/GTP	0.025	0.015	-10000	0	-10000	0	0
mol:GDP	0.026	0.037	-10000	0	-0.41	1	1
ARF6/GTP/RAB11FIP3/RAB11A	0.036	0.013	-10000	0	-10000	0	0
RHOA	0.019	0	-10000	0	-10000	0	0
PLD1	0.024	0.015	-10000	0	-10000	0	0
RAB11FIP3	0.019	0	-10000	0	-10000	0	0
tube morphogenesis	0.029	0.037	-10000	0	-0.44	1	1
ruffle organization	0.031	0.013	-10000	0	-10000	0	0
regulation of epithelial cell migration	0.013	0.019	-10000	0	-0.23	1	1
PLD2	0.024	0.015	-10000	0	-10000	0	0
PIP5K1A	0.031	0.013	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.03	0.012	-10000	0	-10000	0	0
Rac1/GTP	0.029	0.038	-10000	0	-0.45	1	1

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.019	0	-9999	-10000	0	0
PTK2	0.019	0	-9999	-10000	0	0
CRKL	0.017	0.042	-9999	-0.26	4	4
GRB2/SOS1/SHC	0.038	0	-9999	-10000	0	0
HRAS	0.019	0	-9999	-10000	0	0
IRS1/Crk	0.019	0.043	-9999	-0.26	4	4
IGF-1R heterotetramer/IGF1/PTP1B	0.028	0.041	-9999	-0.3	4	4
AKT1	0.034	0.036	-9999	-10000	0	0
BAD	0.039	0.035	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.017	0.042	-9999	-0.26	4	4
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.02	0.043	-9999	-0.26	4	4
RAF1	0.047	0.033	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.034	0.043	-9999	-0.24	4	4
YWHAZ	0.019	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.013	0.047	-9999	-0.27	5	5
PIK3CA	0.018	0.014	-9999	-0.24	1	1
RPS6KB1	0.034	0.036	-9999	-10000	0	0
GNB2L1	0.019	0	-9999	-10000	0	0
positive regulation of MAPKKK cascade	0.038	0.03	-9999	-10000	0	0
PXN	0.019	0	-9999	-10000	0	0
PIK3R1	0.019	0	-9999	-10000	0	0
cell adhesion	0	0	-9999	-10000	0	0
GRB2/SOS1	0.028	0	-9999	-10000	0	0
HRAS/GTP	-0.006	0.024	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.048	0.034	-9999	-0.22	4	4
IGF-1R heterotetramer	0.014	0.03	-9999	-0.25	4	4
IGF-1R heterotetramer/IGF1/IRS/Nck	0.024	0.044	-9999	-0.26	4	4
Crk/p130 Cas/Paxillin	0.039	0.041	-9999	-0.22	4	4
IGF1R	0.014	0.03	-9999	-0.25	4	4
IGF1	0.008	0.066	-9999	-0.38	9	9
IRS2/Crk	0.027	0.041	-9999	-0.24	4	4
PI3K	0.033	0.043	-9999	-0.24	4	4
apoptosis	-0.046	0.033	-9999	-10000	0	0
HRAS/GDP	0.014	0	-9999	-10000	0	0
PRKCD	0.036	0.044	-9999	-0.34	4	4
RAF1/14-3-3 E	0.054	0.032	-9999	-10000	0	0
BAD/14-3-3	0.048	0.034	-9999	-10000	0	0
PRKCZ	0.033	0.041	-9999	-0.23	2	2
Crk/p130 Cas/Paxillin/FAK1	-0.002	0.018	-9999	-10000	0	0
PTPN1	0.019	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.031	0.047	-9999	-0.37	4	4
BCAR1	0.019	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.038	0.038	-9999	-0.25	4	4
mol:GDP	0	0	-9999	-10000	0	0
SOS1	0.019	0	-9999	-10000	0	0
IRS1/NCK2	0.02	0.043	-9999	-0.26	4	4
GRB10	0.017	0.019	-9999	-0.24	2	2
PTPN11	0.017	0.042	-9999	-0.26	4	4
IRS1	0.009	0.046	-9999	-0.27	5	5
IRS2	0.017	0.042	-9999	-0.26	4	4
IGF-1R heterotetramer/IGF1	0.014	0.052	-9999	-0.36	5	5
GRB2	0.019	0	-9999	-10000	0	0
PDPK1	0.03	0.038	-9999	-0.22	4	4
YWHAE	0.019	0	-9999	-10000	0	0
PRKD1	0.035	0.048	-9999	-0.34	5	5
SHC1	0.019	0	-9999	-10000	0	0

×

Aurora A 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
Aurora A/GADD45A	0.032	0.014	-9999	-10000	0	0
BIRC5	0.019	0	-9999	-10000	0	0
NFKBIA	0.032	0.006	-9999	-10000	0	0
CPEB1	-0.023	0.15	-9999	-0.53	28	28
AKT1	0.032	0.006	-9999	-10000	0	0
NDEL1	0.019	0	-9999	-10000	0	0
Aurora A/BRCA1	0.03	0.005	-9999	-10000	0	0
NDEL1/TACC3	0.041	0.004	-9999	-10000	0	0
GADD45A	0.017	0.024	-9999	-0.24	3	3
GSK3B	0.018	0.004	-9999	-10000	0	0
PAK1/Aurora A	0.033	0.009	-9999	-10000	0	0
MDM2	0.015	0.033	-9999	-0.24	6	6
JUB	0.018	0.014	-9999	-0.24	1	1
TPX2	0.026	0	-9999	-10000	0	0
TP53	0.033	0.014	-9999	-10000	0	0
DLG7	0.022	0.006	-9999	-10000	0	0
AURKAIP1	0.019	0	-9999	-10000	0	0
ARHGEF7	0.019	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	0.043	0.005	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.03	0.005	-9999	-10000	0	0
AURKA	0.028	0.008	-9999	-10000	0	0
AURKB	0.017	0.025	-9999	-0.43	1	1
CDC25B	0.033	0.006	-9999	-10000	0	0
G2/M transition checkpoint	0.029	0.008	-9999	-10000	0	0
mRNA polyadenylation	0.006	0.082	-9999	-0.28	27	27
Aurora A/CPEB	0.006	0.083	-9999	-0.29	27	27
Aurora A/TACC1/TRAP/chTOG	0.052	0.017	-9999	-0.25	1	1
BRCA1	0.019	0	-9999	-10000	0	0
centrosome duplication	0.033	0.009	-9999	-10000	0	0
regulation of centrosome cycle	0.039	0.004	-9999	-10000	0	0
spindle assembly	0.051	0.016	-9999	-0.25	1	1
TDRD7	0.017	0.029	-9999	-0.54	1	1
Aurora A/RasGAP/Survivin	0.048	0.016	-9999	-0.24	1	1
CENPA	0.021	0.027	-9999	-0.34	2	2
Aurora A/PP2A	0.033	0.005	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.038	0.008	-9999	-10000	0	0
negative regulation of DNA binding	0.033	0.014	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0.028	0	-9999	-10000	0	0
RASA1	0.017	0.029	-9999	-0.54	1	1
Ajuba/Aurora A	0.03	0.008	-9999	-10000	0	0
mitotic prometaphase	0	0.004	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.028	0.008	-9999	-10000	0	0
TACC1	0.019	0	-9999	-10000	0	0
TACC3	0.019	0	-9999	-10000	0	0
Aurora A/Antizyme1	0.043	0.005	-9999	-10000	0	0
Aurora A/RasGAP	0.032	0.019	-9999	-0.32	1	1
OAZ1	0.019	0	-9999	-10000	0	0
RAN	0.019	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.018	0.004	-9999	-10000	0	0
GIT1	0.019	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0.038	0.008	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	0.026	0	-9999	-10000	0	0
PPP2R5D	0.019	0	-9999	-10000	0	0
Aurora A/TPX2	0.039	0.005	-9999	-10000	0	0
PAK1	0.018	0.014	-9999	-0.24	1	1
CKAP5	0.019	0	-9999	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.025	0.009	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.043	0.007	-10000	0	-10000	0	0
CDKN1B	0.041	0.008	-10000	0	-10000	0	0
CDKN1A	0.04	0.013	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.019	0	-10000	0	-10000	0	0
FOXO3	0.041	0.008	-10000	0	-10000	0	0
AKT1	0.035	0.008	-10000	0	-10000	0	0
BAD	0.019	0	-10000	0	-10000	0	0
AKT3	0.02	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.041	0.008	-10000	0	-10000	0	0
AKT1/ASK1	0.041	0.022	-10000	0	-0.23	2	2
BAD/YWHAZ	0.038	0	-10000	0	-10000	0	0
RICTOR	0.017	0.029	-10000	0	-0.54	1	1
RAF1	0.019	0	-10000	0	-10000	0	0
JNK cascade	-0.039	0.021	0.22	2	-10000	0	2
TSC1	0.041	0.008	-10000	0	-10000	0	0
YWHAZ	0.019	0	-10000	0	-10000	0	0
AKT1/RAF1	0.045	0.008	-10000	0	-10000	0	0
EP300	0.019	0	-10000	0	-10000	0	0
mol:GDP	0.035	0.008	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.041	0.008	-10000	0	-10000	0	0
YWHAQ	0.019	0	-10000	0	-10000	0	0
TBC1D4	0.024	0.023	-10000	0	-0.31	1	1
MAP3K5	0.016	0.041	-10000	0	-0.54	2	2
MAPKAP1	0.019	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.041	0.02	-10000	0	-10000	0	0
YWHAH	0.019	0	-10000	0	-10000	0	0
AKT1S1	0.041	0.008	-10000	0	-10000	0	0
CASP9	0.041	0.008	-10000	0	-10000	0	0
YWHAB	0.019	0	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.05	0.008	-10000	0	-10000	0	0
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.037	0.019	-10000	0	-0.32	1	1
YWHAE	0.019	0	-10000	0	-10000	0	0
SRC	0.019	0	-10000	0	-10000	0	0
AKT2/p21CIP1	0.045	0.012	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.022	0.003	-10000	0	-10000	0	0
CHUK	0.041	0.008	-10000	0	-10000	0	0
BAD/BCL-XL	0.059	0.01	-10000	0	-10000	0	0
mTORC2	0.023	0.017	-10000	0	-0.3	1	1
AKT2	0.02	0	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.057	0.023	-10000	0	-10000	0	0
PDPK1	0.019	0	-10000	0	-10000	0	0
MDM2	0.039	0.016	-10000	0	-10000	0	0
MAPKKK cascade	-0.044	0.008	-10000	0	-10000	0	0
MDM2/Cbp/p300	0.058	0.016	-10000	0	-10000	0	0
TSC1/TSC2	0.046	0.007	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.055	0.015	-10000	0	-10000	0	0
glucose import	0.019	0.038	-10000	0	-0.28	1	1
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.035	0.006	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	0.019	0.039	-10000	0	-0.28	1	1
GSK3A	0.041	0.008	-10000	0	-10000	0	0
FOXO1	0.041	0.008	-10000	0	-10000	0	0
GSK3B	0.041	0.008	-10000	0	-10000	0	0
SFN	-0.034	0.1	-10000	0	-0.24	73	73
G1/S transition of mitotic cell cycle	0.046	0.007	-10000	0	-10000	0	0
p27Kip1/14-3-3 family	0.042	0.028	-10000	0	-10000	0	0
PRKACA	0.019	0	-10000	0	-10000	0	0
KPNA1	0.019	0	-10000	0	-10000	0	0
HSP90AA1	0.017	0.029	-10000	0	-0.54	1	1
YWHAG	0.019	0	-10000	0	-10000	0	0
RHEB	0.019	0	-10000	0	-10000	0	0
CREBBP	0.019	0	-10000	0	-10000	0	0

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	0.003	0.022	-10000	0	-10000	0	0
oxygen homeostasis	0.008	0.013	-10000	0	-10000	0	0
TCEB2	0.017	0.029	-10000	0	-0.54	1	1
TCEB1	0.019	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	0.092	0.065	-10000	0	-10000	0	0
EPO	0.14	0.14	-10000	0	-0.48	2	2
FIH (dimer)	0.026	0.032	-10000	0	-0.53	1	1
APEX1	0.028	0.014	-10000	0	-10000	0	0
SERPINE1	0.13	0.17	-10000	0	-0.6	2	2
FLT1	0.024	0.035	-10000	0	-10000	0	0
ADORA2A	0.11	0.18	-10000	0	-0.47	14	14
germ cell development	0.13	0.15	-10000	0	-0.58	2	2
SLC11A2	0.13	0.15	-10000	0	-0.56	2	2
BHLHE40	0.13	0.16	-10000	0	-0.56	2	2
HIF1AN	0.026	0.032	-10000	0	-0.53	1	1
HIF2A/ARNT/SIRT1	0.11	0.1	-10000	0	-0.29	1	1
ETS1	0.036	0.005	-10000	0	-10000	0	0
CITED2	0.021	0.027	-10000	0	-10000	0	0
KDR	0.021	0.045	-10000	0	-10000	0	0
PGK1	0.13	0.15	-10000	0	-0.56	2	2
SIRT1	0.019	0	-10000	0	-10000	0	0
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	0.16	0.18	-10000	0	-0.64	2	2
EPAS1	0.078	0.077	-10000	0	-0.28	1	1
SP1	0.028	0.002	-10000	0	-10000	0	0
ABCG2	0.11	0.21	-10000	0	-0.52	23	23
EFNA1	0.13	0.15	-10000	0	-0.56	2	2
FXN	0.13	0.15	-10000	0	-0.54	2	2
POU5F1	0.13	0.16	-10000	0	-0.6	2	2
neuron apoptosis	-0.16	0.18	0.63	2	-10000	0	2
EP300	0.019	0	-10000	0	-10000	0	0
EGLN3	0.023	0.047	-10000	0	-0.38	4	4
EGLN2	0.027	0.012	-10000	0	-10000	0	0
EGLN1	0.027	0.012	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.037	0.019	-10000	0	-0.32	1	1
VHL	0.019	0	-10000	0	-10000	0	0
ARNT	0.029	0.014	-10000	0	-10000	0	0
SLC2A1	0.12	0.15	-10000	0	-0.54	2	2
TWIST1	0.076	0.18	-10000	0	-0.64	2	2
ELK1	0.028	0	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.12	0.1	-10000	0	-10000	0	0
VEGFA	0.13	0.16	-10000	0	-0.6	2	2
CREBBP	0.019	0	-10000	0	-10000	0	0

×

Arf6 trafficking events

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
SLC2A4	-0.001	0.07	-10000	0	-0.24	28	28
CLTC	0.037	0	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.03	0	-10000	0	-10000	0	0
Dynamin 2/GTP	0.03	0	-10000	0	-10000	0	0
EXOC4	0.019	0	-10000	0	-10000	0	0
CD59	0.033	0	-10000	0	-10000	0	0
CPE	0.014	0.04	-10000	0	-0.32	3	3
CTNNB1	0.019	0	-10000	0	-10000	0	0
membrane fusion	0.03	0	-10000	0	-10000	0	0
CTNND1	0.034	0	-10000	0	-10000	0	0
DNM2	0.019	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.036	0	-10000	0	-10000	0	0
TSHR	-0.009	0.097	-10000	0	-0.32	31	31
INS	0.013	0	-10000	0	-10000	0	0
BIN1	-0.005	0.11	-10000	0	-0.54	16	16
mol:Choline	0.03	0	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.022	0	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.019	0	-10000	0	-10000	0	0
mol:Ca2+	0.03	0	-10000	0	-10000	0	0
JUP	0.03	0.013	-10000	0	-10000	0	0
ASAP2/amphiphysin II	0.022	0.066	-10000	0	-0.29	16	16
ARF6/GTP	0.014	0	-10000	0	-10000	0	0
CDH1	-0.028	0.098	-10000	0	-10000	0	0
clathrin-independent pinocytosis	0.014	0	-10000	0	-10000	0	0
MAPK8IP3	0.018	0.014	-10000	0	-0.24	1	1
positive regulation of endocytosis	0.014	0	-10000	0	-10000	0	0
EXOC2	0.019	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.049	0.016	-10000	0	-0.24	1	1
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.019	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.001	0.073	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.022	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.025	0.008	-10000	0	-10000	0	0
ACAP1	-0.016	0.064	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.027	0	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.032	0.015	-10000	0	-10000	0	0
JIP4/KLC1	0.036	0	-10000	0	-10000	0	0
EXOC1	0.019	0	-10000	0	-10000	0	0
exocyst	0.049	0.016	-10000	0	-0.24	1	1
RALA/GTP	0.014	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.026	0	-10000	0	-10000	0	0
receptor recycling	0.014	0	-10000	0	-10000	0	0
CTNNA1	0.034	0	-10000	0	-10000	0	0
NME1	0.022	0	-10000	0	-10000	0	0
clathrin coat assembly	0.037	0	-10000	0	-10000	0	0
IL2RA	-0.023	0.096	-10000	0	-10000	0	0
VAMP3	0.022	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.006	0.02	-10000	0	-10000	0	0
EXOC6	0.017	0.029	-10000	0	-0.54	1	1
PLD1	0.026	0	-10000	0	-10000	0	0
PLD2	0.026	0	-10000	0	-10000	0	0
EXOC5	0.019	0	-10000	0	-10000	0	0
PIP5K1C	0.036	0	-10000	0	-10000	0	0
SDC1	0.028	0.031	-10000	0	-10000	0	0
ARF6/GDP	0.024	0	-10000	0	-10000	0	0
EXOC7	0.019	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.002	0.075	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.03	0	-10000	0	-10000	0	0
endocytosis	-0.021	0.066	0.29	16	-10000	0	16
SCAMP2	0.019	0	-10000	0	-10000	0	0
ADRB2	0.04	0.029	-10000	0	-0.23	4	4
EXOC3	0.018	0.014	-10000	0	-0.24	1	1
ASAP2	0.019	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.032	0	-10000	0	-10000	0	0
KLC1	0.019	0	-10000	0	-10000	0	0
AVPR2	0.037	0.027	-10000	0	-10000	0	0
RALA	0.019	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.013	0.07	-10000	0	-10000	0	0

×

VEGFR1 specific signals

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.04	0.012	-9999	-10000	0	0
VEGFR1 homodimer/NRP1	0.026	0.012	-9999	-10000	0	0
mol:DAG	0.033	0.057	-9999	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	0.029	0.034	-9999	-0.29	1	1
CaM/Ca2+	0.042	0.054	-9999	-10000	0	0
HIF1A	0.029	0.008	-9999	-10000	0	0
GAB1	0.019	0	-9999	-10000	0	0
AKT1	0.052	0.055	-9999	-10000	0	0
PLCG1	0.033	0.057	-9999	-10000	0	0
NOS3	0.056	0.064	-9999	-0.59	1	1
CBL	0.019	0	-9999	-10000	0	0
mol:NO	0.056	0.062	-9999	-0.57	1	1
FLT1	0.036	0.015	-9999	-10000	0	0
PGF	0.001	0.099	-9999	-0.54	12	12
VEGFR1 homodimer/NRP2/VEGFR121	0.041	0.039	-9999	-0.28	1	1
CALM1	0.019	0	-9999	-10000	0	0
PIK3CA	0.018	0.014	-9999	-0.24	1	1
eNOS/Hsp90	0.064	0.062	-9999	-0.55	1	1
endothelial cell proliferation	-0.03	0.14	-9999	-0.53	9	9
mol:Ca2+	0.033	0.057	-9999	-10000	0	0
MAPK3	0.039	0.054	-9999	-10000	0	0
MAPK1	0.039	0.054	-9999	-10000	0	0
PIK3R1	0.019	0	-9999	-10000	0	0
PLGF homodimer	0.001	0.099	-9999	-0.54	12	12
PRKACA	0.019	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	0.019	0	-9999	-10000	0	0
VEGFA homodimer	0.004	0.061	-9999	-0.24	21	21
VEGFR1 homodimer/VEGFA homodimer	0.032	0.038	-9999	-0.32	1	1
platelet activating factor biosynthetic process	0.044	0.053	-9999	-10000	0	0
PI3K	0.049	0.056	-9999	-10000	0	0
PRKCA	0.034	0.058	-9999	-10000	0	0
PRKCB	-0.052	0.15	-9999	-0.52	8	8
VEGFR1 homodimer/PLGF homodimer	0.029	0.064	-9999	-0.31	12	12
VEGFA	0.004	0.061	-9999	-0.24	21	21
VEGFB	0.019	0	-9999	-10000	0	0
mol:IP3	0.033	0.057	-9999	-10000	0	0
RASA1	0.042	0.02	-9999	-10000	0	0
NRP2	0.017	0.029	-9999	-0.54	1	1
VEGFR1 homodimer	0.036	0.015	-9999	-10000	0	0
VEGFB homodimer	0.019	0	-9999	-10000	0	0
NCK1	0.019	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.064	0.061	-9999	-0.55	1	1
PTPN11	0.019	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.047	0.055	-9999	-10000	0	0
mol:L-citrulline	0.056	0.062	-9999	-0.57	1	1
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.051	0.038	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.042	0.036	-9999	-0.28	1	1
CD2AP	0.017	0.029	-9999	-0.54	1	1
PI3K/GAB1	0.056	0.054	-9999	-10000	0	0
PDPK1	0.044	0.051	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.042	0.036	-9999	-0.28	1	1
mol:NADP	0.056	0.062	-9999	-0.57	1	1
HSP90AA1	0.017	0.029	-9999	-0.54	1	1
ubiquitin-dependent protein catabolic process	0.049	0.037	-9999	-10000	0	0
VEGFR1 homodimer/NRP2	0.039	0.022	-9999	-0.31	1	1

×

Arf1 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.024	0	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.024	0	-9999	-10000	0	0
AP2	0.028	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0.027	0	-9999	-10000	0	0
CLTB	0.019	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.03	0	-9999	-10000	0	0
CD4	-0.034	0.16	-9999	-0.54	35	35
CLTA	0.019	0	-9999	-10000	0	0
mol:GTP	0.002	0	-9999	-10000	0	0
ARFGAP1	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.015	0	-9999	-10000	0	0
ARF1/GTP	0.023	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.03	0	-9999	-10000	0	0
mol:Choline	0.015	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.019	0	-9999	-10000	0	0
DDEF1	0.015	0	-9999	-10000	0	0
ARF1/GDP	0.01	0	-9999	-10000	0	0
AP2M1	0.019	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0.02	0	-9999	-10000	0	0
Rac/GTP	0.015	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.034	0	-9999	-10000	0	0
ARFIP2	0.017	0	-9999	-10000	0	0
COPA	0.019	0	-9999	-10000	0	0
RAC1	0.019	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.029	0	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0.013	0	-9999	-10000	0	0
GGA3	0.019	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0.024	0	-9999	-10000	0	0
AP2A1	0.019	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.031	0	-9999	-10000	0	0
ARF1/GDP/Membrin	0.024	0	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0.025	0	-9999	-10000	0	0
CYTH2	0.019	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0.026	0	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0.014	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	0.018	0.07	-9999	-0.2	35	35
PLD2	0.015	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.013	0	-9999	-10000	0	0
PIP5K1A	0.015	0	-9999	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0.027	0	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0.015	0	-9999	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	0.013	0	-9999	-10000	0	0
GOSR2	0.018	0	-9999	-10000	0	0
USO1	0.018	0	-9999	-10000	0	0
GBF1	0.018	0	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0.027	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.004	0.1	-9999	-0.32	35	35

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
SMAD4	0.019	-9999	-9999
SMAD2	0.015	-9999	-9999
SMAD3	0.046	-9999	-9999
SMAD3/SMAD4	0.056	-9999	-9999
SMAD4/Ubc9/PIASy	0.038	-9999	-9999
SMAD2/SMAD2/SMAD4	0.053	-9999	-9999
PPM1A	0.019	-9999	-9999
CALM1	0.019	-9999	-9999
SMAD2/SMAD4	0.026	-9999	-9999
MAP3K1	0.019	-9999	-9999
TRAP-1/SMAD4	0.028	-9999	-9999
MAPK3	0.019	-9999	-9999
MAPK1	0.019	-9999	-9999
NUP214	0.019	-9999	-9999
CTDSP1	0.019	-9999	-9999
CTDSP2	0.019	-9999	-9999
CTDSPL	0.019	-9999	-9999
KPNB1	0.019	-9999	-9999
TGFBRAP1	0.019	-9999	-9999
UBE2I	0.019	-9999	-9999
NUP153	0.019	-9999	-9999
KPNA2	0.019	-9999	-9999
PIAS4	0.019	-9999	-9999

×

BARD1 signaling events

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
BARD1/CSTF1	0.028	0.001	-9999	-10000	0	0
ATM	0.019	0	-9999	-10000	0	0
UBE2D3	0.019	0	-9999	-10000	0	0
PRKDC	0.019	0	-9999	-10000	0	0
ATR	0.019	0	-9999	-10000	0	0
UBE2L3	0.019	0	-9999	-10000	0	0
FANCD2	0.031	0	-9999	-10000	0	0
protein ubiquitination	0.051	0.001	-9999	-10000	0	0
XRCC5	0.019	0	-9999	-10000	0	0
XRCC6	0.019	0	-9999	-10000	0	0
M/R/N Complex	0.036	0.026	-9999	-0.32	2	2
MRE11A	0.019	0	-9999	-10000	0	0
DNA-PK	0.038	0	-9999	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.061	0	-9999	-10000	0	0
FANCF	0.019	0	-9999	-10000	0	0
BRCA1	0.019	0	-9999	-10000	0	0
CCNE1	0.019	0	-9999	-10000	0	0
CDK2/Cyclin E1	0.028	0	-9999	-10000	0	0
FANCG	0.019	0	-9999	-10000	0	0
BRCA1/BACH1/BARD1	0.028	0.001	-9999	-10000	0	0
FANCE	0.019	0	-9999	-10000	0	0
FANCC	0.019	0	-9999	-10000	0	0
NBN	0.019	0	-9999	-10000	0	0
FANCA	0.019	0	-9999	-10000	0	0
DNA repair	0.08	0	-9999	-10000	0	0
BRCA1/BARD1/ubiquitin	0.028	0.001	-9999	-10000	0	0
BARD1/DNA-PK	0.049	0.001	-9999	-10000	0	0
FANCL	0.019	0	-9999	-10000	0	0
mRNA polyadenylation	-0.028	0.001	-9999	-10000	0	0
BRCA1/BARD1/CTIP/M/R/N Complex	0.045	0.02	-9999	-10000	0	0
BRCA1/BACH1/BARD1/TopBP1	0.038	0.001	-9999	-10000	0	0
BRCA1/BARD1/P53	0.049	0.001	-9999	-10000	0	0
BARD1/CSTF1/BRCA1	0.038	0.001	-9999	-10000	0	0
BRCA1/BACH1	0.019	0	-9999	-10000	0	0
BARD1	0.019	0.001	-9999	-10000	0	0
PCNA	0.019	0	-9999	-10000	0	0
BRCA1/BARD1/UbcH5C	0.038	0.001	-9999	-10000	0	0
BRCA1/BARD1/UbcH7	0.038	0.001	-9999	-10000	0	0
BRCA1/BARD1/RAD51/PCNA	0.049	0.001	-9999	-10000	0	0
BARD1/DNA-PK/P53	0.056	0.001	-9999	-10000	0	0
BRCA1/BARD1/Ubiquitin	0.028	0.001	-9999	-10000	0	0
BRCA1/BARD1/CTIP	0.043	0.001	-9999	-10000	0	0
FA complex	0.047	0	-9999	-10000	0	0
BARD1/EWS	0.028	0.001	-9999	-10000	0	0
RBBP8	0.026	0	-9999	-10000	0	0
TP53	0.019	0	-9999	-10000	0	0
TOPBP1	0.019	0	-9999	-10000	0	0
G1/S transition of mitotic cell cycle	-0.047	0.001	-9999	-10000	0	0
BRCA1/BARD1	0.056	0.001	-9999	-10000	0	0
CSTF1	0.019	0	-9999	-10000	0	0
BARD1/EWS-Fli1	0.014	0.001	-9999	-10000	0	0
CDK2	0.019	0	-9999	-10000	0	0
UniProt:Q9BZD1	0	0	-9999	-10000	0	0
RAD51	0.019	0	-9999	-10000	0	0
RAD50	0.016	0.041	-9999	-0.54	2	2
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.028	0.001	-9999	-10000	0	0
EWSR1	0.019	0	-9999	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.019	0	-9999	-10000	0	0
PLK4	0.017	0.029	-9999	-0.54	1	1
regulation of centriole replication	0.025	0.021	-9999	-0.38	1	1

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.059	0.009	-9999	-10000	0	0
CLOCK	0.022	0.014	-9999	-0.24	1	1
TIMELESS/CRY2	0.051	0.01	-9999	-10000	0	0
DEC1/BMAL1	0.016	0.021	-9999	-0.39	1	1
ATR	0.019	0	-9999	-10000	0	0
NR1D1	0.047	0.011	-9999	-10000	0	0
ARNTL	0.021	0.029	-9999	-0.53	1	1
TIMELESS	0.047	0.011	-9999	-10000	0	0
NPAS2	0.017	0.058	-9999	-0.53	4	4
CRY2	0.019	0	-9999	-10000	0	0
mol:CO	-0.016	0	-9999	-10000	0	0
CHEK1	0.019	0	-9999	-10000	0	0
mol:HEME	0.016	0	-9999	-10000	0	0
PER1	0.019	0	-9999	-10000	0	0
BMAL/CLOCK/NPAS2	0.053	0.043	-9999	-0.3	5	5
BMAL1/CLOCK	0.057	0.025	-9999	-10000	0	0
S phase of mitotic cell cycle	0.059	0.009	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	0.06	0.01	-9999	-10000	0	0
mol:NADPH	0.016	0	-9999	-10000	0	0
PER1/TIMELESS	0.051	0.01	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	0	0	-9999	-10000	0	0

×

PLK1 signaling events

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
regulation of centriole-centriole cohesion	-0.013	0.001	-9999	-10000	0	0
BUB1B	0.027	0.016	-9999	-0.27	1	1
PLK1	0.022	0.002	-9999	-10000	0	0
PLK1S1	0.019	0.001	-9999	-10000	0	0
KIF2A	0.027	0.002	-9999	-10000	0	0
regulation of mitotic centrosome separation	0.022	0.002	-9999	-10000	0	0
GOLGA2	0.019	0	-9999	-10000	0	0
Hec1/SPC24	0.038	0.031	-9999	-0.26	4	4
WEE1	0.031	0.001	-9999	-10000	0	0
cytokinesis	0.038	0.022	-9999	-0.39	1	1
PP2A-alpha B56	0.05	0	-9999	-10000	0	0
AURKA	0.02	0.001	-9999	-10000	0	0
PICH/PLK1	0.042	0.02	-9999	-0.22	2	2
CENPE	0.021	0.042	-9999	-0.28	7	7
RhoA/GTP	0.014	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.027	0.002	-9999	-10000	0	0
PPP2CA	0.019	0	-9999	-10000	0	0
FZR1	0.019	0	-9999	-10000	0	0
TPX2	0.019	0.001	-9999	-10000	0	0
PAK1	0.018	0.014	-9999	-0.24	1	1
SPC24	0.017	0.029	-9999	-0.54	1	1
FBXW11	0.019	0	-9999	-10000	0	0
CLSPN	0.018	0.023	-9999	-0.29	2	2
GORASP1	0.019	0	-9999	-10000	0	0
metaphase	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NLP	0.012	0.001	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
STAG2	0.019	0	-9999	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.03	0	-9999	-10000	0	0
spindle elongation	0.022	0.002	-9999	-10000	0	0
ODF2	0.019	0	-9999	-10000	0	0
BUB1	0.031	0	-9999	-10000	0	0
TPT1	0.019	0.001	-9999	-10000	0	0
CDC25C	0.021	0.02	-9999	-0.36	1	1
CDC25B	0.02	0	-9999	-10000	0	0
SGOL1	0.013	0.001	-9999	-10000	0	0
RHOA	0.019	0	-9999	-10000	0	0
CCNB1/CDK1	0.033	0	-9999	-10000	0	0
CDC14B	0.013	0	-9999	-10000	0	0
CDC20	0.019	0	-9999	-10000	0	0
PLK1/PBIP1	0.02	0.033	-9999	-0.26	5	5
mitosis	0	0	-9999	-10000	0	0
FBXO5	0.025	0.001	-9999	-10000	0	0
CDC2	0.002	0	-9999	-10000	0	0
NDC80	0.014	0.05	-9999	-0.54	3	3
metaphase plate congression	0.02	0.001	-9999	-10000	0	0
ERCC6L	0.041	0.02	-9999	-0.23	2	2
NLP/gamma Tubulin	0.017	0.001	-9999	-10000	0	0
microtubule cytoskeleton organization	0.019	0.001	-9999	-10000	0	0
G2/M transition DNA damage checkpoint	0	0	-9999	-10000	0	0
PPP1R12A	0.019	0	-9999	-10000	0	0
interphase	0	0	-9999	-10000	0	0
PLK1/PRC1-2	0.041	0.016	-9999	-0.26	1	1
GRASP65/GM130/RAB1/GTP/PLK1	0.047	0.001	-9999	-10000	0	0
RAB1A	0.019	0	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
Aurora A/BORA	0.023	0.002	-9999	-10000	0	0
mitotic prometaphase	0	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.042	0.001	-9999	-10000	0	0
microtubule-based process	0.03	0.016	-9999	-0.28	1	1
Golgi organization	0.022	0.002	-9999	-10000	0	0
Cohesin/SA2	0.027	0.002	-9999	-10000	0	0
PPP1CB/MYPT1	0.028	0	-9999	-10000	0	0
KIF20A	0.017	0.029	-9999	-0.54	1	1
APC/C/CDC20	0.031	0.002	-9999	-10000	0	0
PPP2R1A	0.019	0	-9999	-10000	0	0
chromosome segregation	0.019	0.032	-9999	-0.25	5	5
PRC1	0.019	0	-9999	-10000	0	0
ECT2	0.027	0.002	-9999	-10000	0	0
C13orf34	0.023	0.002	-9999	-10000	0	0
NUDC	0.02	0.001	-9999	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	0.027	0.016	-9999	-0.27	1	1
spindle assembly	0.021	0.002	-9999	-10000	0	0
spindle stabilization	0.019	0.001	-9999	-10000	0	0
APC/C/HCDH1	0.024	0	-9999	-10000	0	0
MKLP2/PLK1	0.03	0.016	-9999	-0.28	1	1
CCNB1	0.02	0	-9999	-10000	0	0
PPP1CB	0.019	0	-9999	-10000	0	0
BTRC	0.019	0	-9999	-10000	0	0
ROCK2	0.03	0.001	-9999	-10000	0	0
TUBG1	0.019	0.001	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0	0	-9999	-10000	0	0
MLF1IP	0.008	0.048	-9999	-0.4	5	5
INCENP	0.019	0	-9999	-10000	0	0

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.019	0	-10000	0	-10000	0	0
mol:PIP3	-0.005	0.024	0.27	1	-10000	0	1
FRAP1	0.016	0.008	-10000	0	-10000	0	0
AKT1	0.023	0.024	0.22	1	-10000	0	1
INSR	0.018	0.014	-10000	0	-0.24	1	1
Insulin Receptor/Insulin	0.012	0.008	-10000	0	-10000	0	0
mol:GTP	0.036	0.02	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0	0	-10000	0	-10000	0	0
TSC2	0.019	0	-10000	0	-10000	0	0
RHEB/GDP	-0.001	0.005	-10000	0	-10000	0	0
TSC1	0.019	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.013	0.029	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.001	0.004	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.019	0	-10000	0	-10000	0	0
RPS6KB1	0.028	0.015	0.18	1	-10000	0	1
MAP3K5	0.01	0.028	-10000	0	-0.37	2	2
PIK3R1	0.019	0	-10000	0	-10000	0	0
apoptosis	0.01	0.028	-10000	0	-0.37	2	2
mol:LY294002	0	0	-10000	0	-10000	0	0
EIF4B	0.032	0.015	0.18	1	-10000	0	1
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.041	0.011	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	0	0	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.025	0.028	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.031	0.012	0.17	1	-10000	0	1
FKBP1A	0.019	0	-10000	0	-10000	0	0
RHEB/GTP	0.038	0.017	-10000	0	-10000	0	0
mol:Amino Acids	0	0	-10000	0	-10000	0	0
FKBP12/Rapamycin	0.014	0.001	-10000	0	-10000	0	0
PDPK1	0.018	0.025	0.23	1	-10000	0	1
EIF4E	0.019	0	-10000	0	-10000	0	0
ASK1/PP5C	0.026	0.048	-10000	0	-0.61	2	2
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.021	0.001	-10000	0	-10000	0	0
TSC1/TSC2	0.041	0.023	0.22	1	-10000	0	1
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RPS6	0.019	0	-10000	0	-10000	0	0
PPP5C	0.019	0	-10000	0	-10000	0	0
EIF4G1	0.019	0	-10000	0	-10000	0	0
IRS1	0.002	0.029	-10000	0	-10000	0	0
INS	0	0	-10000	0	-10000	0	0
PTEN	0.017	0.029	-10000	0	-0.54	1	1
PDK2	0.017	0.026	0.23	1	-10000	0	1
EIF4EBP1	0.017	0.013	-10000	0	-10000	0	0
PIK3CA	0.018	0.014	-10000	0	-0.24	1	1
PPP2R5D	0.021	0.008	-10000	0	-10000	0	0
peptide biosynthetic process	0.02	0.007	-10000	0	-10000	0	0
RHEB	0.019	0	-10000	0	-10000	0	0
EIF4A1	0.019	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	0.003	1	-10000	0	1
EEF2	0.02	0.007	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.027	0.012	-10000	0	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.017	0.029	-9999	-0.54	1	1
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
MDM2/SUMO1	0.038	0.015	-9999	-10000	0	0
HDAC4	0.019	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	-0.001	0.011	-9999	-0.21	1	1
SUMO1	0.019	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.02	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.031	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.019	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.019	0	-9999	-10000	0	0
SUMO1/HDAC4	0.04	0	-9999	-10000	0	0
SUMO1/HDAC1	0.039	0.015	-9999	-0.25	1	1
RANGAP1	0.019	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	0.046	0.018	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.025	0	-9999	-10000	0	0
Ran/GTP	0.033	0	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.015	0.033	-9999	-0.24	6	6
UBE2I	0.019	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.039	0	-9999	-10000	0	0
NPC	0.011	0	-9999	-10000	0	0
PIAS2	0.019	0	-9999	-10000	0	0
PIAS1	0.019	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
IKK alpha homodimer	0.028	-9999	-9999
FBXW11	0.019	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	0	-9999	-9999
beta TrCP1/SCF ubiquitin ligase complex	0.019	-9999	-9999
CHUK	0.019	-9999	-9999
NF kappa B2 p100/RelB	0.056	-9999	-9999
NFKB1	0.019	-9999	-9999
MAP3K14	0.019	-9999	-9999
NF kappa B1 p50/RelB	0.028	-9999	-9999
RELB	0.019	-9999	-9999
NFKB2	0.019	-9999	-9999
NF kappa B2 p52/RelB	0.026	-9999	-9999
regulation of B cell activation	0.025	-9999	-9999

pid_entity	TCGA.Z2.AA3V	TCGA.Z2.AA3S	TCGA.Z2.A8RT	TCGA.YG.AA3P
109_MAP3K5	0.061	-0.017	0.061	-0.28
47_PPARGC1A	0.019	0.019	0.019	0.019
105_BMP4	0.019	0.019	0.019	0.019
105_BMP6	0.019	0.019	0.019	0.019
105_BMP7	-0.24	0.019	0.019	0.019
105_BMP2	0.019	0.019	0.019	0.019
131_RELN/VLDLR	0.049	0.049	0.049	0.049
30_TGFB1/TGF beta receptor Type II	0.018	0.018	0.018	0.018
84_STAT5B	0.043	0.042	-0.029	0.055
84_STAT5A	0.043	0.042	-0.029	0.055