PARADIGM pathway analysis of mRNASeq expression data - Lung Adenocarcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
Glypican 2 network	186
Angiopoietin receptor Tie2-mediated signaling	141
FOXM1 transcription factor network	133
Aurora B signaling	121
Signaling events mediated by the Hedgehog family	100
Aurora C signaling	74
Endothelins	71
PLK1 signaling events	69
HIF-1-alpha transcription factor network	66
Visual signal transduction: Cones	60

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
Glypican 2 network	0.3811	186	746	4	-0.21	-0.13	1000	-1000	-0.028	-1000
Angiopoietin receptor Tie2-mediated signaling	0.2889	141	12424	88	-0.6	0.057	1000	-1000	-0.095	-1000
FOXM1 transcription factor network	0.2725	133	6794	51	-0.56	0.01	1000	-1000	-0.19	-1000
Aurora B signaling	0.2480	121	8142	67	-0.41	0.01	1000	-1000	-0.062	-1000
Signaling events mediated by the Hedgehog family	0.2049	100	5203	52	-0.37	0.18	1000	-1000	-0.066	-1000
Aurora C signaling	0.1516	74	519	7	-0.27	0.005	1000	-1000	-0.035	-1000
Endothelins	0.1455	71	6826	96	-0.3	0.022	1000	-1000	-0.071	-1000
PLK1 signaling events	0.1414	69	5895	85	-0.3	0.06	1000	-1000	-0.041	-1000
HIF-1-alpha transcription factor network	0.1352	66	5090	76	-0.49	0.016	1000	-1000	-0.16	-1000
Visual signal transduction: Cones	0.1230	60	2284	38	-0.17	0.01	1000	-1000	-0.053	-1000
Signaling mediated by p38-alpha and p38-beta	0.1209	59	2631	44	-0.12	0.01	1000	-1000	-0.046	-1000
Osteopontin-mediated events	0.1189	58	2205	38	-0.36	0.011	1000	-1000	-0.084	-1000
Signaling events regulated by Ret tyrosine kinase	0.1127	55	4542	82	-0.16	0.01	1000	-1000	-0.072	-1000
IL4-mediated signaling events	0.1086	53	4836	91	-0.79	0.52	1000	-1000	-0.18	-1000
amb2 Integrin signaling	0.1045	51	4245	82	-0.46	0.01	1000	-1000	-0.067	-1000
BMP receptor signaling	0.1004	49	4021	81	-0.35	0.027	1000	-1000	-0.078	-1000
Fc-epsilon receptor I signaling in mast cells	0.0984	48	4679	97	-0.15	0.028	1000	-1000	-0.076	-1000
FOXA2 and FOXA3 transcription factor networks	0.0963	47	2165	46	-0.49	0.016	1000	-1000	-0.085	-1000
TCGA08_retinoblastoma	0.0922	45	366	8	-0.15	0.05	1000	-1000	-0.016	-1000
Glucocorticoid receptor regulatory network	0.0861	42	4849	114	-0.42	0.25	1000	-1000	-0.059	-1000
TCGA08_p53	0.0861	42	294	7	-0.1	0.054	1000	-1000	-0.01	-1000
Syndecan-1-mediated signaling events	0.0820	40	1365	34	-0.34	0.01	1000	-1000	-0.049	-1000
Visual signal transduction: Rods	0.0779	38	1992	52	-0.15	0.01	1000	-1000	-0.072	-1000
Arf6 signaling events	0.0758	37	2350	62	-0.19	0.012	1000	-1000	-0.059	-1000
p75(NTR)-mediated signaling	0.0758	37	4711	125	-0.29	0.019	1000	-1000	-0.089	-1000
LPA4-mediated signaling events	0.0738	36	436	12	-0.12	0.013	1000	-1000	-0.019	-1000
Canonical Wnt signaling pathway	0.0717	35	1817	51	-0.34	0.15	1000	-1000	-0.058	-1000
Thromboxane A2 receptor signaling	0.0697	34	3664	105	-0.089	0.029	1000	-1000	-0.061	-1000
Glypican 1 network	0.0676	33	1584	48	-0.12	0.019	1000	-1000	-0.039	-1000
Effects of Botulinum toxin	0.0656	32	833	26	-0.09	0.01	1000	-1000	-0.053	-1000
Ephrin B reverse signaling	0.0635	31	1515	48	-0.093	0.054	1000	-1000	-0.051	-1000
Integrins in angiogenesis	0.0635	31	2670	84	-0.36	0.025	1000	-1000	-0.071	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0635	31	3761	120	-0.25	0.2	1000	-1000	-0.066	-1000
EGFR-dependent Endothelin signaling events	0.0615	30	633	21	-0.089	0.01	1000	-1000	-0.061	-1000
ErbB4 signaling events	0.0574	28	2000	69	-0.19	0.21	1000	-1000	-0.073	-1000
IL23-mediated signaling events	0.0574	28	1699	60	-0.28	0.015	1000	-1000	-0.16	-1000
Presenilin action in Notch and Wnt signaling	0.0533	26	1597	61	-0.34	0.021	1000	-1000	-0.066	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0533	26	1815	68	-0.14	0.028	1000	-1000	-0.12	-1000
IL6-mediated signaling events	0.0512	25	1898	75	-0.33	0.042	1000	-1000	-0.089	-1000
Aurora A signaling	0.0492	24	1451	60	-0.29	0.015	1000	-1000	-0.059	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0492	24	808	33	-0.15	0.025	1000	-1000	-0.048	-1000
PDGFR-alpha signaling pathway	0.0471	23	1012	44	-0.32	0.027	1000	-1000	-0.047	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0430	21	1143	52	-0.26	0.044	1000	-1000	-0.051	-1000
Nongenotropic Androgen signaling	0.0430	21	1141	52	-0.057	0.01	1000	-1000	-0.052	-1000
Wnt signaling	0.0430	21	147	7	-0.059	0.009	1000	-1000	-0.029	-1000
Class IB PI3K non-lipid kinase events	0.0430	21	63	3	-0.012	-1000	1000	-1000	-0.015	-1000
HIF-2-alpha transcription factor network	0.0410	20	866	43	-0.13	0.064	1000	-1000	-0.087	-1000
Reelin signaling pathway	0.0389	19	1082	56	-0.095	0.01	1000	-1000	-0.066	-1000
Regulation of Androgen receptor activity	0.0389	19	1357	70	-0.26	0.027	1000	-1000	-0.062	-1000
PLK2 and PLK4 events	0.0369	18	54	3	-0.018	-0.003	1000	-1000	-0.017	-1000
Syndecan-4-mediated signaling events	0.0369	18	1224	67	-0.17	0.016	1000	-1000	-0.074	-1000
Coregulation of Androgen receptor activity	0.0328	16	1252	76	-0.15	0.018	1000	-1000	-0.047	-1000
Syndecan-2-mediated signaling events	0.0328	16	1123	69	-0.096	0.032	1000	-1000	-0.049	-1000
Nectin adhesion pathway	0.0328	16	1015	63	-0.041	0.013	1000	-1000	-0.063	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0307	15	541	34	-0.04	0.01	1000	-1000	-0.053	-1000
Noncanonical Wnt signaling pathway	0.0307	15	405	26	-0.059	0.01	1000	-1000	-0.076	-1000
IL12-mediated signaling events	0.0287	14	1256	87	-0.097	0.038	1000	-1000	-0.12	-1000
Syndecan-3-mediated signaling events	0.0287	14	517	35	-0.2	0.01	1000	-1000	-0.057	-1000
Caspase cascade in apoptosis	0.0266	13	962	74	-0.041	0.032	1000	-1000	-0.043	-1000
Signaling events mediated by PTP1B	0.0266	13	1034	76	-0.092	0.017	1000	-1000	-0.07	-1000
Signaling events mediated by HDAC Class III	0.0266	13	526	40	-0.11	0.018	1000	-1000	-0.039	-1000
FAS signaling pathway (CD95)	0.0266	13	612	47	-0.24	0.012	1000	-1000	-0.042	-1000
EPHB forward signaling	0.0266	13	1122	85	-0.066	0.049	1000	-1000	-0.08	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0266	13	1682	125	-0.32	0.034	1000	-1000	-0.084	-1000
LPA receptor mediated events	0.0266	13	1378	102	-0.12	0.03	1000	-1000	-0.074	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0266	13	1060	78	-0.039	0.038	1000	-1000	-0.072	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0246	12	659	54	-0.14	0.021	1000	-1000	-0.085	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0246	12	1053	85	-0.041	0.03	1000	-1000	-0.068	-1000
IL1-mediated signaling events	0.0246	12	759	62	-0.15	0.049	1000	-1000	-0.083	-1000
S1P1 pathway	0.0246	12	462	36	-0.063	0.011	1000	-1000	-0.05	-1000
TCR signaling in naïve CD8+ T cells	0.0246	12	1136	93	-0.075	0.043	1000	-1000	-0.069	-1000
BCR signaling pathway	0.0246	12	1256	99	-0.13	0.026	1000	-1000	-0.078	-1000
Signaling events mediated by PRL	0.0246	12	429	34	-0.18	0.021	1000	-1000	-0.034	-1000
BARD1 signaling events	0.0225	11	656	57	-0.18	0.03	1000	-1000	-0.053	-1000
Ephrin A reverse signaling	0.0225	11	77	7	-0.01	0.008	1000	-1000	-0.024	-1000
S1P5 pathway	0.0225	11	199	17	-0.033	0.03	1000	-1000	-0.048	-1000
S1P4 pathway	0.0225	11	280	25	-0.033	0.011	1000	-1000	-0.046	-1000
Calcium signaling in the CD4+ TCR pathway	0.0205	10	339	31	-0.073	0.012	1000	-1000	-0.085	-1000
ErbB2/ErbB3 signaling events	0.0184	9	631	65	-0.095	0.019	1000	-1000	-0.063	-1000
Regulation of p38-alpha and p38-beta	0.0184	9	523	54	-0.075	0.018	1000	-1000	-0.053	-1000
IL2 signaling events mediated by STAT5	0.0184	9	203	22	-0.12	0.055	1000	-1000	-0.061	-1000
Regulation of nuclear SMAD2/3 signaling	0.0164	8	1142	136	-0.11	0.051	1000	-1000	-0.06	-1000
Plasma membrane estrogen receptor signaling	0.0164	8	763	86	-0.035	0.03	1000	-1000	-0.074	-1000
Signaling mediated by p38-gamma and p38-delta	0.0143	7	119	15	0	0.022	1000	-1000	-0.025	-1000
IL27-mediated signaling events	0.0143	7	378	51	-0.11	0.011	1000	-1000	-0.064	-1000
Ras signaling in the CD4+ TCR pathway	0.0143	7	133	17	-0.014	0.021	1000	-1000	-0.043	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0123	6	192	28	-0.033	0.021	1000	-1000	-0.048	-1000
Cellular roles of Anthrax toxin	0.0123	6	238	39	-0.045	0.015	1000	-1000	-0.022	-1000
Retinoic acid receptors-mediated signaling	0.0123	6	362	58	-0.17	0.032	1000	-1000	-0.063	-1000
Arf6 trafficking events	0.0123	6	465	71	-0.081	0.034	1000	-1000	-0.064	-1000
Regulation of Telomerase	0.0123	6	712	102	-0.092	0.03	1000	-1000	-0.094	-1000
Insulin Pathway	0.0123	6	469	74	-0.15	0.03	1000	-1000	-0.079	-1000
VEGFR1 specific signals	0.0123	6	375	56	-0.32	0.042	1000	-1000	-0.069	-1000
p38 MAPK signaling pathway	0.0123	6	287	44	-0.082	0.025	1000	-1000	-0.058	-1000
Signaling events mediated by HDAC Class II	0.0102	5	400	75	-0.046	0.027	1000	-1000	-0.054	-1000
JNK signaling in the CD4+ TCR pathway	0.0102	5	89	17	-0.013	0.031	1000	-1000	-0.055	-1000
Hedgehog signaling events mediated by Gli proteins	0.0102	5	382	65	-0.17	0.054	1000	-1000	-0.056	-1000
Ceramide signaling pathway	0.0102	5	417	76	-0.089	0.036	1000	-1000	-0.052	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0102	5	433	83	-0.067	0.04	1000	-1000	-0.072	-1000
FoxO family signaling	0.0102	5	330	64	-0.13	0.055	1000	-1000	-0.081	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0102	5	373	74	-0.11	0.06	1000	-1000	-0.076	-1000
IFN-gamma pathway	0.0082	4	310	68	-0.082	0.047	1000	-1000	-0.084	-1000
Signaling events mediated by HDAC Class I	0.0082	4	484	104	-0.046	0.043	1000	-1000	-0.059	-1000
IL2 signaling events mediated by PI3K	0.0082	4	272	58	-0.15	0.066	1000	-1000	-0.079	-1000
Class I PI3K signaling events	0.0082	4	362	73	-0.075	0.023	1000	-1000	-0.067	-1000
Circadian rhythm pathway	0.0061	3	79	22	-0.029	0.034	1000	-1000	-0.064	-1000
Arf6 downstream pathway	0.0061	3	164	43	-0.039	0.026	1000	-1000	-0.037	-1000
TCGA08_rtk_signaling	0.0061	3	96	26	-0.023	0.037	1000	-1000	-0.02	-1000
S1P3 pathway	0.0061	3	154	42	-0.032	0.023	1000	-1000	-0.053	-1000
TRAIL signaling pathway	0.0041	2	128	48	-0.008	0.04	1000	-1000	-0.055	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0041	2	117	45	-0.012	0.062	1000	-1000	-0.083	-1000
E-cadherin signaling in the nascent adherens junction	0.0041	2	187	76	-0.041	0.05	1000	-1000	-0.069	-1000
IGF1 pathway	0.0041	2	168	57	-0.037	0.04	1000	-1000	-0.083	-1000
Rapid glucocorticoid signaling	0.0041	2	59	20	-0.007	0.01	1000	-1000	-0.029	-1000
PDGFR-beta signaling pathway	0.0041	2	226	97	-0.036	0.048	1000	-1000	-0.07	-1000
Canonical NF-kappaB pathway	0.0020	1	44	39	-0.014	0.066	1000	-1000	-0.069	-1000
a4b1 and a4b7 Integrin signaling	0.0020	1	8	5	-0.002	0.009	1000	-1000	-0.032	-1000
EPO signaling pathway	0.0020	1	83	55	-0.006	0.058	1000	-1000	-0.085	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0020	1	59	37	-0.005	0.037	1000	-1000	-0.048	-1000
ceramide signaling pathway	0.0020	1	55	49	-0.012	0.04	1000	-1000	-0.043	-1000
E-cadherin signaling events	0.0020	1	8	5	-0.002	0.01	1000	-1000	-0.039	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	11	23	-0.003	0.036	1000	-1000	-0.06	-1000
Insulin-mediated glucose transport	0.0000	0	24	32	-0.003	0.035	1000	-1000	-0.059	-1000
mTOR signaling pathway	0.0000	0	13	53	-0.001	0.026	1000	-1000	-0.05	-1000
Class I PI3K signaling events mediated by Akt	0.0000	0	25	68	-0.034	0.046	1000	-1000	-0.055	-1000
Paxillin-dependent events mediated by a4b1	0.0000	0	21	36	-0.003	0.018	1000	-1000	-0.059	-1000
Atypical NF-kappaB pathway	0.0000	0	17	31	-0.002	0.038	1000	-1000	-0.045	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	11	27	-0.001	0.024	1000	-1000	-0.049	-1000
E-cadherin signaling in keratinocytes	0.0000	0	28	43	-0.007	0.037	1000	-1000	-0.055	-1000
Arf1 pathway	0.0000	0	30	54	-0.006	0.024	1000	-1000	-0.035	-1000
Alternative NF-kappaB pathway	0.0000	0	0	13	0	0.01	1000	-1000	-0.053	-1000
Total	NA	2938	169893	7203	-19	-1000	131000	-131000	-8.2	-131000

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.15	0.24	-9999	-0.52	151	151
GPC2	-0.13	0.23	-9999	-0.52	131	131
GPC2/Midkine	-0.21	0.23	-9999	-0.43	232	232
neuron projection morphogenesis	-0.21	0.23	-9999	-0.43	232	232

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.42	0.52	-10000	0	-0.95	229	229
NCK1/PAK1/Dok-R	-0.21	0.22	-10000	0	-0.43	229	229
NCK1/Dok-R	-0.54	0.61	-10000	0	-1.1	229	229
PIK3CA	0.011	0.001	-10000	0	-10000	0	0
mol:beta2-estradiol	0.057	0.1	0.24	113	-10000	0	113
RELA	0.01	0	-10000	0	-10000	0	0
SHC1	0.006	0.024	-10000	0	-0.52	1	1
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	0.003	0.21	0.25	110	-0.52	53	163
TNIP2	0.01	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.49	0.54	-10000	0	-1	229	229
FN1	0.005	0.052	-10000	0	-0.5	5	5
PLD2	-0.52	0.66	-10000	0	-1.2	229	229
PTPN11	0.01	0	-10000	0	-10000	0	0
GRB14	-0.026	0.13	-10000	0	-0.51	33	33
ELK1	-0.45	0.57	-10000	0	-1	229	229
GRB7	0.004	0.057	-10000	0	-0.51	6	6
PAK1	0.01	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.52	0.58	-10000	0	-1.1	229	229
CDKN1A	-0.28	0.35	-10000	0	-0.65	227	227
ITGA5	0.008	0.033	-10000	0	-0.51	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.54	0.61	-10000	0	-1.1	229	229
CRK	0.01	0	-10000	0	-10000	0	0
mol:NO	-0.29	0.37	-10000	0	-0.68	229	229
PLG	-0.53	0.66	-10000	0	-1.2	229	229
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.39	0.48	-10000	0	-0.89	229	229
GRB2	0.01	0	-10000	0	-10000	0	0
PIK3R1	0.005	0.024	-10000	0	-0.5	1	1
ANGPT2	-0.21	0.29	-10000	0	-0.64	127	127
BMX	-0.6	0.7	-10000	0	-1.3	229	229
ANGPT1	-0.3	0.53	-10000	0	-1.3	113	113
tube development	-0.32	0.4	-10000	0	-0.73	228	228
ANGPT4	-0.25	0.25	-10000	0	-0.5	248	248
response to hypoxia	-0.029	0.035	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.56	0.69	-10000	0	-1.2	229	229
alpha5/beta1 Integrin	-0.001	0.023	-10000	0	-0.36	2	2
FGF2	-0.059	0.17	-10000	0	-0.5	66	66
STAT5A (dimer)	-0.37	0.46	-10000	0	-0.85	227	227
mol:L-citrulline	-0.29	0.37	-10000	0	-0.68	229	229
AGTR1	-0.15	0.24	-10000	0	-0.5	153	153
MAPK14	-0.55	0.67	-10000	0	-1.2	229	229
Tie2/SHP2	-0.47	0.55	-10000	0	-1.1	203	203
TEK	-0.51	0.62	-10000	0	-1.2	203	203
RPS6KB1	-0.39	0.49	-10000	0	-0.91	229	229
Angiotensin II/AT1	-0.11	0.17	-10000	0	-0.36	153	153
Tie2/Ang1/GRB2	-0.54	0.69	-10000	0	-1.2	229	229
MAPK3	-0.46	0.59	-10000	0	-1.1	229	229
MAPK1	-0.46	0.59	-10000	0	-1.1	229	229
Tie2/Ang1/GRB7	-0.55	0.69	-10000	0	-1.2	229	229
NFKB1	0.01	0	-10000	0	-10000	0	0
MAPK8	-0.52	0.66	-10000	0	-1.2	229	229
PI3K	-0.5	0.61	-10000	0	-1.1	229	229
FES	-0.55	0.67	-10000	0	-1.2	229	229
Crk/Dok-R	-0.54	0.61	-10000	0	-1.1	229	229
Tie2/Ang1/ABIN2	-0.54	0.69	-10000	0	-1.2	229	229
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.36	0.45	-10000	0	-0.83	229	229
STAT5A	0.009	0.023	-10000	0	-0.5	1	1
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.39	0.49	-10000	0	-0.91	229	229
Tie2/Ang2	-0.47	0.57	-10000	0	-1.1	228	228
Tie2/Ang1	-0.59	0.75	-10000	0	-1.3	229	229
FOXO1	-0.36	0.46	-10000	0	-0.84	229	229
ELF1	-0.028	0.051	-10000	0	-10000	0	0
ELF2	-0.53	0.67	-10000	0	-1.2	229	229
mol:Choline	-0.49	0.62	-10000	0	-1.1	229	229
cell migration	-0.11	0.12	-10000	0	-0.24	229	229
FYN	-0.38	0.46	-10000	0	-0.85	228	228
DOK2	-0.031	0.14	-10000	0	-0.5	39	39
negative regulation of cell cycle	-0.25	0.32	-10000	0	-0.58	227	227
ETS1	-0.045	0.1	-10000	0	-0.26	19	19
PXN	-0.31	0.4	-10000	0	-0.73	229	229
ITGB1	0.01	0	-10000	0	-10000	0	0
NOS3	-0.34	0.43	-10000	0	-0.78	229	229
RAC1	0.01	0	-10000	0	-10000	0	0
TNF	-0.064	0.14	-10000	0	-0.54	19	19
MAPKKK cascade	-0.49	0.62	-10000	0	-1.1	229	229
RASA1	0.01	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.56	0.68	-10000	0	-1.2	229	229
NCK1	0.01	0	-10000	0	-10000	0	0
vasculogenesis	-0.25	0.33	-10000	0	-0.6	229	229
mol:Phosphatidic acid	-0.49	0.62	-10000	0	-1.1	229	229
mol:Angiotensin II	0.001	0.002	-10000	0	-10000	0	0
mol:NADP	-0.29	0.37	-10000	0	-0.68	229	229
Rac1/GTP	-0.4	0.42	-10000	0	-0.84	229	229
MMP2	-0.52	0.66	-10000	0	-1.2	229	229

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.43	0.55	-9999	-1	163	163
PLK1	-0.15	0.2	-9999	-0.37	216	216
BIRC5	-0.19	0.2	-9999	-10000	0	0
HSPA1B	-0.44	0.55	-9999	-1	173	173
MAP2K1	-0.001	0.034	-9999	-10000	0	0
BRCA2	-0.44	0.55	-9999	-1	163	163
FOXM1	-0.56	0.7	-9999	-1.3	192	192
XRCC1	-0.43	0.55	-9999	-1	161	161
FOXM1B/p19	-0.51	0.49	-9999	-1.1	181	181
Cyclin D1/CDK4	-0.43	0.51	-9999	-0.97	173	173
CDC2	-0.46	0.58	-9999	-1.1	191	191
TGFA	-0.42	0.5	-9999	-0.95	167	167
SKP2	-0.44	0.55	-9999	-1	167	167
CCNE1	-0.19	0.26	-9999	-0.53	178	178
CKS1B	-0.44	0.55	-9999	-1	168	168
RB1	-0.22	0.18	-9999	-0.44	138	138
FOXM1C/SP1	-0.5	0.61	-9999	-1.2	180	180
AURKB	-0.17	0.2	-9999	-10000	0	0
CENPF	-0.49	0.59	-9999	-1.1	195	195
CDK4	0.002	0.05	-9999	-0.54	4	4
MYC	-0.38	0.48	-9999	-0.9	167	167
CHEK2	-0.008	0.071	-9999	-0.57	6	6
ONECUT1	-0.47	0.55	-9999	-1	182	182
CDKN2A	-0.14	0.24	-9999	-0.51	145	145
LAMA4	-0.44	0.55	-9999	-1	172	172
FOXM1B/HNF6	-0.56	0.65	-9999	-1.2	182	182
FOS	-0.46	0.57	-9999	-1.1	172	172
SP1	0.01	0.001	-9999	-10000	0	0
CDC25B	-0.43	0.55	-9999	-1	167	167
response to radiation	-0.012	0.032	-9999	-10000	0	0
CENPB	-0.43	0.55	-9999	-1	163	163
CENPA	-0.51	0.6	-9999	-1.1	191	191
NEK2	-0.51	0.6	-9999	-1.1	202	202
HIST1H2BA	-0.44	0.55	-9999	-1	163	163
CCNA2	-0.12	0.23	-9999	-0.53	119	119
EP300	0.01	0	-9999	-10000	0	0
CCNB1/CDK1	-0.52	0.64	-9999	-1.2	175	175
CCNB2	-0.5	0.6	-9999	-1.1	192	192
CCNB1	-0.48	0.6	-9999	-1.1	174	174
ETV5	-0.44	0.55	-9999	-1.1	162	162
ESR1	-0.45	0.56	-9999	-1.1	166	166
CCND1	-0.44	0.52	-9999	-0.99	175	175
GSK3A	0.002	0.028	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	-0.18	0.26	-9999	-0.45	210	210
CDK2	0.006	0.008	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.016	0.038	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.55	0.5	-9999	-1.1	197	197
GAS1	-0.45	0.56	-9999	-1.1	160	160
MMP2	-0.44	0.55	-9999	-1	161	161
RB1/FOXM1C	-0.47	0.56	-9999	-1.1	181	181
CREBBP	0.01	0	-9999	-10000	0	0

×

Aurora B signaling

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
Condensin I complex	-0.15	0.17	-9999	-0.33	202	202
STMN1	-0.18	0.19	-9999	-0.36	255	255
Aurora B/RasGAP/Survivin	-0.31	0.27	-9999	-0.51	304	304
Chromosomal passenger complex/Cul3 protein complex	-0.13	0.14	-9999	-0.3	155	155
BIRC5	-0.3	0.26	-9999	-0.53	281	281
DES	-0.41	0.37	-9999	-0.74	262	262
Aurora C/Aurora B/INCENP	-0.14	0.15	-9999	-0.28	259	259
Aurora B/TACC1	-0.16	0.17	-9999	-0.32	261	261
Aurora B/PP2A	-0.18	0.19	-9999	-0.36	255	255
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.033	0.045	-9999	-10000	0	0
mitotic metaphase/anaphase transition	-0.003	0.004	-9999	-10000	0	0
NDC80	-0.34	0.32	-9999	-0.59	284	284
Cul3 protein complex	-0.013	0.063	-9999	-0.31	21	21
KIF2C	-0.12	0.11	-9999	-0.22	264	264
PEBP1	0.004	0.005	-9999	-10000	0	0
KIF20A	-0.28	0.26	-9999	-0.52	267	267
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.18	0.19	-9999	-0.36	255	255
SEPT1	0.009	0.023	-9999	-0.5	1	1
SMC2	0.01	0	-9999	-10000	0	0
SMC4	0.01	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.064	0.076	-9999	-10000	0	0
PSMA3	0.01	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.002	0.004	-9999	-10000	0	0
H3F3B	-0.09	0.1	-9999	-0.18	255	255
AURKB	-0.26	0.27	-9999	-0.52	255	255
AURKC	0.005	0.052	-9999	-0.51	5	5
CDCA8	-0.17	0.25	-9999	-0.53	162	162
cytokinesis	-0.23	0.21	-9999	-0.45	207	207
Aurora B/Septin1	-0.21	0.2	-9999	-0.44	183	183
AURKA	-0.094	0.21	-9999	-0.52	96	96
INCENP	0.003	0.007	-9999	-10000	0	0
KLHL13	-0.01	0.099	-9999	-0.5	19	19
BUB1	-0.13	0.24	-9999	-0.52	131	131
hSgo1/Aurora B/Survivin	-0.41	0.36	-9999	-0.65	311	311
EVI5	0.009	0.002	-9999	-10000	0	0
RhoA/GTP	-0.22	0.22	-9999	-0.48	177	177
SGOL1	-0.24	0.26	-9999	-0.52	228	228
CENPA	-0.16	0.16	-9999	-0.31	241	241
NCAPG	-0.23	0.26	-9999	-0.52	220	220
Aurora B/HC8 Proteasome	-0.18	0.19	-9999	-0.36	255	255
NCAPD2	0.009	0.024	-9999	-0.52	1	1
Aurora B/PP1-gamma	-0.18	0.19	-9999	-0.36	255	255
RHOA	0.01	0	-9999	-10000	0	0
NCAPH	-0.22	0.26	-9999	-0.52	211	211
NPM1	-0.085	0.083	-9999	-10000	0	0
RASA1	0.01	0	-9999	-10000	0	0
KLHL9	0.007	0.04	-9999	-0.5	3	3
mitotic prometaphase	-0.009	0.008	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.18	0.19	-9999	-0.36	255	255
PPP1CC	0.01	0	-9999	-10000	0	0
Centraspindlin	-0.24	0.24	-9999	-0.47	215	215
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.085	0.083	-9999	-10000	0	0
MYLK	-0.1	0.12	-9999	-0.2	258	258
KIF23	-0.11	0.22	-9999	-0.53	104	104
VIM	-0.18	0.19	-9999	-0.36	255	255
RACGAP1	0	0.054	-9999	-0.53	5	5
mitosis	0	0	-9999	-10000	0	0
NCL	-0.085	0.083	-9999	-10000	0	0
Chromosomal passenger complex	-0.2	0.2	-9999	-0.38	245	245
Chromosomal passenger complex/EVI5	-0.33	0.32	-9999	-0.63	244	244
TACC1	-0.011	0.1	-9999	-0.5	20	20
PPP2R5D	0.01	0	-9999	-10000	0	0
CUL3	0.01	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.21	0.25	-10000	0	-0.65	85	85
IHH	-0.31	0.27	-10000	0	-0.54	276	276
SHH Np/Cholesterol/GAS1	-0.04	0.1	-10000	0	-0.28	71	71
LRPAP1	0.01	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.04	0.1	0.28	71	-10000	0	71
SMO/beta Arrestin2	-0.21	0.21	-10000	0	-0.5	97	97
SMO	-0.22	0.23	-10000	0	-0.51	110	110
AKT1	-0.092	0.11	-10000	0	-0.34	10	10
ARRB2	0.01	0	-10000	0	-10000	0	0
BOC	0.008	0.033	-10000	0	-0.51	2	2
ADRBK1	0.01	0	-10000	0	-10000	0	0
heart looping	-0.22	0.22	-10000	0	-0.5	110	110
STIL	-0.19	0.22	-10000	0	-0.48	134	134
DHH N/PTCH2	-0.029	0.097	-10000	0	-0.35	40	40
DHH N/PTCH1	-0.19	0.19	-10000	0	-0.49	93	93
PIK3CA	0.01	0	-10000	0	-10000	0	0
DHH	-0.031	0.14	-10000	0	-0.5	39	39
PTHLH	-0.27	0.29	-10000	0	-0.77	85	85
determination of left/right symmetry	-0.22	0.22	-10000	0	-0.5	110	110
PIK3R1	0.009	0.023	-10000	0	-0.5	1	1
skeletal system development	-0.27	0.28	-10000	0	-0.76	85	85
IHH N/Hhip	-0.37	0.26	-10000	0	-0.49	368	368
DHH N/Hhip	-0.22	0.2	-10000	0	-0.38	280	280
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.22	0.22	-10000	0	-0.5	110	110
pancreas development	-0.27	0.25	-10000	0	-0.5	268	268
HHAT	0.008	0.032	-10000	0	-0.5	2	2
PI3K	-0.001	0.016	-10000	0	-0.35	1	1
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.004	0.082	-10000	0	-0.5	13	13
somite specification	-0.22	0.22	-10000	0	-0.5	110	110
SHH Np/Cholesterol/PTCH1	-0.17	0.19	-10000	0	-0.46	108	108
SHH Np/Cholesterol/PTCH2	-0.034	0.088	-10000	0	-0.26	63	63
SHH Np/Cholesterol/Megalin	-0.1	0.15	-10000	0	-0.29	173	173
SHH	-0.029	0.12	-10000	0	-0.35	62	62
catabolic process	-0.2	0.2	-10000	0	-0.49	86	86
SMO/Vitamin D3	-0.2	0.21	-10000	0	-0.51	105	105
SHH Np/Cholesterol/Hhip	-0.18	0.16	-10000	0	-0.3	288	288
LRP2	-0.13	0.22	-10000	0	-0.5	130	130
receptor-mediated endocytosis	-0.25	0.22	-10000	0	-0.52	166	166
SHH Np/Cholesterol/BOC	-0.035	0.089	-10000	0	-0.26	64	64
SHH Np/Cholesterol/CDO	-0.039	0.097	-10000	0	-0.27	71	71
mesenchymal cell differentiation	0.18	0.16	0.3	288	-10000	0	288
mol:Vitamin D3	-0.18	0.2	-10000	0	-0.46	108	108
IHH N/PTCH2	-0.18	0.16	-10000	0	-0.32	276	276
CDON	-0.002	0.075	-10000	0	-0.5	11	11
IHH N/PTCH1	-0.2	0.2	-10000	0	-0.49	86	86
Megalin/LRPAP1	-0.094	0.16	-10000	0	-0.35	130	130
PTCH2	0.009	0.023	-10000	0	-0.5	1	1
SHH Np/Cholesterol	-0.034	0.09	-10000	0	-0.27	62	62
PTCH1	-0.2	0.2	-10000	0	-0.49	86	86
HHIP	-0.27	0.25	-10000	0	-0.5	268	268

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.01	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.15	0.14	-9999	-0.28	259	259
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.042	0.04	-9999	-10000	0	0
AURKB	-0.27	0.26	-9999	-0.52	255	255
AURKC	0.005	0.052	-9999	-0.51	5	5

×

Endothelins

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
AKT1	-0.052	0.2	-10000	0	-0.53	37	37
PTK2B	0.008	0.033	-10000	0	-0.5	2	2
mol:Ca2+	-0.051	0.28	-10000	0	-0.94	37	37
EDN1	-0.07	0.23	-10000	0	-0.54	79	79
EDN3	-0.13	0.22	-10000	0	-0.5	134	134
EDN2	-0.14	0.24	-10000	0	-0.52	139	139
HRAS/GDP	-0.083	0.2	-10000	0	-0.46	68	68
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.006	0.13	-10000	0	-0.39	26	26
ADCY4	-0.069	0.17	-10000	0	-0.48	46	46
ADCY5	-0.089	0.2	-10000	0	-0.52	59	59
ADCY6	-0.056	0.16	-10000	0	-0.47	39	39
ADCY7	-0.057	0.16	-10000	0	-0.47	40	40
ADCY1	-0.062	0.16	-10000	0	-0.47	43	43
ADCY2	-0.082	0.18	-10000	0	-0.5	53	53
ADCY3	-0.056	0.16	-10000	0	-0.47	38	38
ADCY8	-0.17	0.19	-10000	0	-0.45	97	97
ADCY9	-0.061	0.16	-10000	0	-0.48	41	41
arachidonic acid secretion	-0.071	0.2	-10000	0	-0.49	63	63
ETB receptor/Endothelin-1/Gq/GTP	-0.16	0.2	-10000	0	-0.36	172	172
GNAO1	0.004	0.057	-10000	0	-0.51	6	6
HRAS	0.01	0.002	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	0.022	0.22	0.23	154	-0.5	37	191
ETA receptor/Endothelin-1/Gs/GTP	0.013	0.22	0.22	152	-0.48	42	194
mol:GTP	0	0.005	-10000	0	-10000	0	0
COL3A1	-0.11	0.26	-10000	0	-0.49	123	123
EDNRB	-0.29	0.25	-10000	0	-0.5	287	287
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.061	0.22	-10000	0	-0.63	38	38
CYSLTR1	-0.065	0.23	-10000	0	-0.66	40	40
SLC9A1	-0.024	0.11	0.18	1	-0.29	33	34
mol:GDP	-0.095	0.22	-10000	0	-0.5	70	70
SLC9A3	-0.3	0.36	-10000	0	-0.54	292	292
RAF1	-0.094	0.21	-10000	0	-0.51	63	63
JUN	-0.02	0.19	-10000	0	-0.67	25	25
JAK2	-0.053	0.2	0.26	1	-0.52	41	42
mol:IP3	-0.093	0.18	-10000	0	-0.39	82	82
ETA receptor/Endothelin-1	-0.028	0.28	0.26	163	-0.52	62	225
PLCB1	0.008	0.024	-10000	0	-0.52	1	1
PLCB2	-0.001	0.072	-10000	0	-0.5	10	10
ETA receptor/Endothelin-3	-0.096	0.18	-10000	0	-0.37	136	136
FOS	-0.09	0.26	-10000	0	-0.83	42	42
Gai/GDP	-0.009	0.083	-10000	0	-0.58	3	3
CRK	0.01	0.001	-10000	0	-10000	0	0
mol:Ca ++	-0.15	0.25	-10000	0	-0.56	101	101
BCAR1	0.009	0.023	-10000	0	-0.5	1	1
PRKCB1	-0.089	0.17	-10000	0	-0.37	85	85
GNAQ	0.01	0.024	-10000	0	-0.5	1	1
GNAZ	-0.033	0.14	-10000	0	-0.5	41	41
GNAL	-0.002	0.076	-10000	0	-0.5	11	11
Gs family/GDP	-0.12	0.17	-10000	0	-0.45	74	74
ETA receptor/Endothelin-1/Gq/GTP	-0.011	0.14	-10000	0	-0.36	42	42
MAPK14	-0.12	0.18	-10000	0	-0.4	89	89
TRPC6	-0.057	0.3	-10000	0	-1	37	37
GNAI2	0.01	0	-10000	0	-10000	0	0
GNAI3	0.01	0	-10000	0	-10000	0	0
GNAI1	0.008	0.032	-10000	0	-0.5	2	2
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.14	0.19	-10000	0	-0.38	127	127
ETB receptor/Endothelin-2	-0.3	0.23	-10000	0	-0.44	337	337
ETB receptor/Endothelin-3	-0.3	0.23	-10000	0	-0.43	337	337
ETB receptor/Endothelin-1	-0.26	0.26	-10000	0	-0.44	293	293
MAPK3	-0.096	0.26	-10000	0	-0.74	49	49
MAPK1	-0.096	0.26	-10000	0	-0.74	49	49
Rac1/GDP	-0.083	0.2	-10000	0	-0.46	68	68
cAMP biosynthetic process	-0.1	0.18	-10000	0	-0.48	66	66
MAPK8	-0.03	0.2	-10000	0	-0.59	40	40
SRC	0.01	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.15	0.18	-10000	0	-0.38	129	129
p130Cas/CRK/Src/PYK2	-0.092	0.23	-10000	0	-0.58	62	62
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.083	0.2	-10000	0	-0.46	68	68
COL1A2	-0.2	0.28	-10000	0	-0.64	105	105
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.1	0.19	-10000	0	-0.38	141	141
mol:DAG	-0.093	0.18	-10000	0	-0.39	82	82
MAP2K2	-0.09	0.22	-10000	0	-0.6	54	54
MAP2K1	-0.09	0.22	-10000	0	-0.61	53	53
EDNRA	0.008	0.1	-10000	0	-0.42	6	6
positive regulation of muscle contraction	-0.037	0.17	-10000	0	-0.48	33	33
Gq family/GDP	-0.076	0.17	-10000	0	-0.49	45	45
HRAS/GTP	-0.099	0.2	-10000	0	-0.45	74	74
PRKCH	-0.083	0.17	-10000	0	-0.45	49	49
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCA	-0.084	0.18	-10000	0	-0.46	50	50
PRKCB	-0.089	0.19	-10000	0	-0.49	54	54
PRKCE	-0.085	0.18	-10000	0	-0.46	51	51
PRKCD	-0.083	0.17	-10000	0	-0.46	49	49
PRKCG	-0.11	0.19	-10000	0	-0.46	73	73
regulation of vascular smooth muscle contraction	-0.11	0.3	-10000	0	-0.98	42	42
PRKCQ	-0.12	0.21	-10000	0	-0.44	102	102
PLA2G4A	-0.078	0.22	-10000	0	-0.54	63	63
GNA14	-0.004	0.086	-10000	0	-0.51	14	14
GNA15	0.01	0.004	-10000	0	-10000	0	0
GNA12	0.01	0	-10000	0	-10000	0	0
GNA11	0.008	0.033	-10000	0	-0.5	2	2
Rac1/GTP	0.022	0.22	0.23	154	-0.5	37	191
MMP1	-0.22	0.2	-10000	0	-0.38	267	267

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0.06	0.072	0.14	228	-10000	0	228
BUB1B	-0.12	0.12	-10000	0	-0.2	296	296
PLK1	-0.025	0.049	-10000	0	-0.11	87	87
PLK1S1	-0.009	0.026	-10000	0	-0.11	1	1
KIF2A	-0.016	0.045	-10000	0	-0.18	1	1
regulation of mitotic centrosome separation	-0.025	0.049	-10000	0	-0.11	87	87
GOLGA2	0.01	0	-10000	0	-10000	0	0
Hec1/SPC24	-0.22	0.26	-10000	0	-0.44	248	248
WEE1	-0.022	0.054	-10000	0	-0.19	1	1
cytokinesis	-0.11	0.13	-10000	0	-0.24	209	209
PP2A-alpha B56	-0.014	0.035	-10000	0	-10000	0	0
AURKA	-0.019	0.044	-10000	0	-0.11	86	86
PICH/PLK1	-0.14	0.22	-10000	0	-0.4	185	185
CENPE	-0.076	0.15	-10000	0	-0.35	103	103
RhoA/GTP	0	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.016	0.044	-10000	0	-0.18	1	1
PPP2CA	0.01	0	-10000	0	-10000	0	0
FZR1	0.01	0	-10000	0	-10000	0	0
TPX2	-0.045	0.053	-10000	0	-0.098	211	211
PAK1	0.008	0.004	-10000	0	-10000	0	0
SPC24	-0.14	0.24	-10000	0	-0.52	143	143
FBXW11	0.01	0	-10000	0	-10000	0	0
CLSPN	-0.038	0.059	-10000	0	-0.13	102	102
GORASP1	0.01	0	-10000	0	-10000	0	0
metaphase	-0.002	0.004	-10000	0	-0.011	85	85
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	-0.013	0.026	-10000	0	-0.058	86	86
G2 phase of mitotic cell cycle	-0.001	0.003	-10000	0	-0.011	2	2
STAG2	0.01	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0	0.011	-10000	0	-10000	0	0
spindle elongation	-0.025	0.049	-10000	0	-0.11	87	87
ODF2	0.008	0.004	-10000	0	-10000	0	0
BUB1	-0.023	0.042	-10000	0	-10000	0	0
TPT1	-0.009	0.026	-10000	0	-0.11	1	1
CDC25C	-0.065	0.061	-10000	0	-0.14	86	86
CDC25B	0.008	0.003	-10000	0	-10000	0	0
SGOL1	-0.06	0.072	-10000	0	-0.14	228	228
RHOA	0.01	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.066	0.11	-10000	0	-0.24	128	128
CDC14B	0.008	0.004	-10000	0	-10000	0	0
CDC20	-0.3	0.26	-10000	0	-0.52	286	286
PLK1/PBIP1	-0.045	0.087	-10000	0	-0.34	34	34
mitosis	-0.003	0.008	0.02	19	-0.018	77	96
FBXO5	-0.016	0.043	-10000	0	-0.17	1	1
CDC2	-0.003	0.005	-10000	0	-0.011	128	128
NDC80	-0.25	0.26	-10000	0	-0.52	237	237
metaphase plate congression	-0.014	0.032	-10000	0	-0.11	1	1
ERCC6L	-0.14	0.19	-10000	0	-0.39	166	166
NLP/gamma Tubulin	-0.011	0.027	-10000	0	-0.11	2	2
microtubule cytoskeleton organization	-0.009	0.026	-10000	0	-0.11	1	1
G2/M transition DNA damage checkpoint	-0.001	0.002	-10000	0	-0.011	1	1
PPP1R12A	0.009	0.001	-10000	0	-10000	0	0
interphase	-0.001	0.002	-10000	0	-0.011	1	1
PLK1/PRC1-2	-0.19	0.22	-10000	0	-0.37	267	267
GRASP65/GM130/RAB1/GTP/PLK1	-0.017	0.027	-10000	0	-10000	0	0
RAB1A	0.01	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	-0.015	0.046	-10000	0	-0.37	1	1
mitotic prometaphase	-0.003	0.003	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.04	0.036	-10000	0	-10000	0	0
microtubule-based process	-0.17	0.17	-10000	0	-0.32	267	267
Golgi organization	-0.025	0.049	-10000	0	-0.11	87	87
Cohesin/SA2	-0.028	0.036	-10000	0	-0.17	1	1
PPP1CB/MYPT1	0	0	-10000	0	-10000	0	0
KIF20A	-0.28	0.26	-10000	0	-0.52	267	267
APC/C/CDC20	-0.18	0.17	-10000	0	-0.32	286	286
PPP2R1A	0.01	0	-10000	0	-10000	0	0
chromosome segregation	-0.045	0.086	-10000	0	-0.33	34	34
PRC1	-0.066	0.18	-10000	0	-0.52	70	70
ECT2	-0.032	0.091	-10000	0	-0.36	29	29
C13orf34	-0.015	0.044	-10000	0	-0.36	1	1
NUDC	-0.014	0.032	-10000	0	-0.11	1	1
regulation of attachment of spindle microtubules to kinetochore	-0.12	0.12	-10000	0	-0.2	296	296
spindle assembly	-0.017	0.04	-10000	0	-0.09	77	77
spindle stabilization	-0.009	0.026	-10000	0	-0.11	1	1
APC/C/HCDH1	0.012	0.005	-10000	0	-10000	0	0
MKLP2/PLK1	-0.17	0.17	-10000	0	-0.33	267	267
CCNB1	-0.13	0.23	-10000	0	-0.52	134	134
PPP1CB	0.009	0.001	-10000	0	-10000	0	0
BTRC	0.01	0	-10000	0	-10000	0	0
ROCK2	-0.008	0.038	-10000	0	-0.4	1	1
TUBG1	-0.009	0.026	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.066	0.1	-10000	0	-0.23	128	128
MLF1IP	-0.022	0.1	-10000	0	-0.39	34	34
INCENP	0.01	0.001	-10000	0	-10000	0	0

×

HIF-1-alpha transcription factor network

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.34	0.47	-9999	-1.1	91	91
HDAC7	0.008	0.007	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.28	0.36	-9999	-0.84	90	90
SMAD4	0.011	0.003	-9999	-10000	0	0
ID2	-0.34	0.47	-9999	-1.1	91	91
AP1	-0.028	0.094	-9999	-0.36	36	36
ABCG2	-0.36	0.5	-9999	-1.1	97	97
HIF1A	-0.041	0.071	-9999	-10000	0	0
TFF3	-0.39	0.51	-9999	-1.1	115	115
GATA2	-0.035	0.14	-9999	-0.5	41	41
AKT1	-0.046	0.08	-9999	-10000	0	0
response to hypoxia	-0.064	0.083	-9999	-0.24	8	8
MCL1	-0.34	0.47	-9999	-1.1	91	91
NDRG1	-0.34	0.47	-9999	-1.1	92	92
SERPINE1	-0.34	0.47	-9999	-1.1	92	92
FECH	-0.34	0.47	-9999	-1.1	91	91
FURIN	-0.34	0.48	-9999	-1.1	93	93
NCOA2	0.007	0.046	-9999	-0.5	4	4
EP300	-0.048	0.11	-9999	-0.33	14	14
HMOX1	-0.34	0.47	-9999	-1.1	90	90
BHLHE40	-0.34	0.47	-9999	-1.1	91	91
BHLHE41	-0.34	0.48	-9999	-1.1	95	95
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.039	0.071	-9999	-0.4	4	4
ENG	-0.012	0.11	-9999	-0.58	6	6
JUN	0.004	0.046	-9999	-0.5	4	4
RORA	-0.34	0.47	-9999	-1.1	92	92
ABCB1	-0.12	0.25	-9999	-1.2	21	21
TFRC	-0.34	0.47	-9999	-1.1	96	96
CXCR4	-0.34	0.47	-9999	-1.1	91	91
TF	-0.39	0.52	-9999	-1.1	117	117
CITED2	-0.34	0.47	-9999	-1.1	91	91
HIF1A/ARNT	-0.38	0.55	-9999	-1.2	104	104
LDHA	-0.046	0.059	-9999	-0.46	1	1
ETS1	-0.34	0.47	-9999	-1.1	91	91
PGK1	-0.34	0.47	-9999	-1.1	92	92
NOS2	-0.36	0.49	-9999	-1.1	107	107
ITGB2	-0.34	0.48	-9999	-1.1	94	94
ALDOA	-0.34	0.47	-9999	-1.1	92	92
Cbp/p300/CITED2	-0.33	0.48	-9999	-1.1	89	89
FOS	-0.025	0.13	-9999	-0.5	32	32
HK2	-0.34	0.47	-9999	-1.1	95	95
SP1	0.015	0.014	-9999	-10000	0	0
GCK	-0.11	0.27	-9999	-1.2	17	17
HK1	-0.34	0.47	-9999	-1.1	91	91
NPM1	-0.34	0.47	-9999	-1.1	91	91
EGLN1	-0.34	0.47	-9999	-1.1	91	91
CREB1	0.016	0.001	-9999	-10000	0	0
PGM1	-0.34	0.47	-9999	-1.1	92	92
SMAD3	0.011	0.003	-9999	-10000	0	0
EDN1	-0.21	0.45	-9999	-1.2	82	82
IGFBP1	-0.37	0.49	-9999	-1.1	104	104
VEGFA	-0.25	0.36	-9999	-0.78	80	80
HIF1A/JAB1	-0.025	0.032	-9999	-10000	0	0
CP	-0.45	0.53	-9999	-1.1	138	138
CXCL12	-0.35	0.48	-9999	-1.1	97	97
COPS5	0.011	0.001	-9999	-10000	0	0
SMAD3/SMAD4	0	0.003	-9999	-10000	0	0
BNIP3	-0.34	0.47	-9999	-1.1	92	92
EGLN3	-0.39	0.52	-9999	-1.1	118	118
CA9	-0.49	0.51	-9999	-1.1	143	143
TERT	-0.4	0.52	-9999	-1.1	114	114
ENO1	-0.34	0.47	-9999	-1.1	91	91
PFKL	-0.34	0.47	-9999	-1.1	90	90
NCOA1	0.01	0	-9999	-10000	0	0
ADM	-0.34	0.47	-9999	-1.1	92	92
ARNT	-0.042	0.071	-9999	-10000	0	0
HNF4A	-0.11	0.22	-9999	-0.52	107	107
ADFP	-0.34	0.47	-9999	-1	103	103
SLC2A1	-0.34	0.42	-9999	-0.88	119	119
LEP	-0.36	0.48	-9999	-1.1	101	101
HIF1A/ARNT/Cbp/p300	-0.29	0.38	-9999	-0.86	96	96
EPO	-0.15	0.27	-9999	-0.78	7	7
CREBBP	-0.048	0.11	-9999	-0.35	12	12
HIF1A/ARNT/Cbp/p300/HDAC7	-0.31	0.39	-9999	-0.91	92	92
PFKFB3	-0.34	0.47	-9999	-1.1	91	91
NT5E	-0.35	0.48	-9999	-1.1	98	98

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	-0.022	0.072	-9999	-0.26	42	42
RGS9BP	-0.066	0.18	-9999	-0.5	73	73
mol:GTP	0	0	-9999	-10000	0	0
GRK1	-0.028	0.13	-9999	-0.52	31	31
mol:Na +	-0.16	0.18	-9999	-0.35	228	228
mol:ADP	-0.014	0.094	-9999	-0.37	32	32
GNAT2	0.007	0.024	-9999	-0.52	1	1
RGS9-1/Gbeta5/R9AP	-0.13	0.17	-9999	-0.32	201	201
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.001	0.02	-9999	-0.31	2	2
GRK7	0.005	0.024	-9999	-0.52	1	1
CNGB3	-0.093	0.2	-9999	-0.52	91	91
Cone Metarhodopsin II/X-Arrestin	-0.002	0.024	-9999	-0.38	2	2
mol:Ca2+	-0.16	0.19	-9999	-0.33	251	251
Cone PDE6	-0.11	0.15	-9999	-0.49	26	26
Cone Metarhodopsin II	-0.019	0.07	-9999	-0.28	32	32
Na + (4 Units)	-0.17	0.18	-9999	-0.33	251	251
GNAT2/GDP	-0.11	0.14	-9999	-0.49	26	26
GNB5	0.01	0	-9999	-10000	0	0
mol:GMP (4 units)	0.008	0.019	-9999	-0.28	2	2
Cone Transducin	-0.024	0.077	-9999	-0.27	42	42
SLC24A2	-0.036	0.14	-9999	-0.52	40	40
GNB3/GNGT2	-0.031	0.1	-9999	-0.36	41	41
GNB3	-0.025	0.13	-9999	-0.52	32	32
GNAT2/GTP	-0.001	0.017	-9999	-0.38	1	1
CNGA3	-0.17	0.25	-9999	-0.52	166	166
ARR3	0	0.033	-9999	-0.52	2	2
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.16	0.19	-9999	-0.35	228	228
mol:Pi	-0.13	0.17	-9999	-0.32	201	201
Cone CNG Channel	-0.13	0.15	-9999	-0.47	36	36
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.036	0.14	-9999	-0.52	40	40
RGS9	-0.15	0.24	-9999	-0.5	153	153
PDE6C	0.003	0.004	-9999	-10000	0	0
GNGT2	0.001	0.068	-9999	-0.5	9	9
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.001	0.024	-9999	-0.52	1	1

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	-0.098	0.33	-9999	-0.98	52	52
MKNK1	0.01	0	-9999	-10000	0	0
MAPK14	-0.031	0.12	-9999	-0.42	9	9
ATF2/c-Jun	-0.016	0.12	-9999	-0.49	13	13
MAPK11	-0.035	0.13	-9999	-0.47	12	12
MITF	-0.037	0.16	-9999	-0.36	90	90
MAPKAPK5	-0.031	0.15	-9999	-0.34	86	86
KRT8	-0.033	0.15	-9999	-0.35	86	86
MAPKAPK3	0.01	0	-9999	-10000	0	0
MAPKAPK2	0.01	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.049	0.18	-9999	-0.43	86	86
CEBPB	-0.031	0.15	-9999	-0.34	86	86
SLC9A1	-0.031	0.15	-9999	-0.34	86	86
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.027	0.15	-9999	-0.34	86	86
p38alpha-beta/MNK1	-0.03	0.15	-9999	-0.34	86	86
JUN	-0.015	0.12	-9999	-0.5	12	12
PPARGC1A	-0.12	0.22	-9999	-0.37	181	181
USF1	-0.031	0.15	-9999	-0.34	86	86
RAB5/GDP/GDI1	-0.045	0.096	-9999	-0.37	12	12
NOS2	-0.091	0.31	-9999	-1	44	44
DDIT3	-0.032	0.15	-9999	-0.34	86	86
RAB5A	0.01	0	-9999	-10000	0	0
HSPB1	-0.019	0.13	-9999	-0.44	13	13
p38alpha-beta/HBP1	-0.03	0.15	-9999	-0.34	86	86
CREB1	-0.032	0.16	-9999	-0.37	86	86
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	-0.021	0.13	-9999	-0.45	12	12
RPS6KA4	-0.031	0.15	-9999	-0.34	86	86
PLA2G4A	-0.061	0.16	-9999	-0.5	22	22
GDI1	-0.031	0.15	-9999	-0.34	86	86
TP53	-0.042	0.18	-9999	-0.42	86	86
RPS6KA5	-0.033	0.15	-9999	-0.35	87	87
ESR1	-0.047	0.18	-9999	-0.38	92	92
HBP1	0.01	0	-9999	-10000	0	0
MEF2C	-0.031	0.15	-9999	-0.34	86	86
MEF2A	-0.031	0.15	-9999	-0.34	86	86
EIF4EBP1	-0.034	0.16	-9999	-0.37	86	86
KRT19	-0.034	0.15	-9999	-0.34	88	88
ELK4	-0.031	0.15	-9999	-0.34	86	86
ATF6	-0.031	0.15	-9999	-0.34	86	86
ATF1	-0.032	0.16	-9999	-0.37	86	86
p38alpha-beta/MAPKAPK2	-0.03	0.15	-9999	-0.34	86	86
p38alpha-beta/MAPKAPK3	-0.03	0.15	-9999	-0.34	86	86

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.18	0.15	-9999	-0.35	85	85
NF kappa B1 p50/RelA/I kappa B alpha	-0.15	0.12	-9999	-0.46	21	21
alphaV/beta3 Integrin/Osteopontin/Src	-0.26	0.16	-9999	-0.36	345	345
AP1	-0.17	0.13	-9999	-0.45	47	47
ILK	-0.19	0.15	-9999	-0.36	86	86
bone resorption	-0.16	0.11	-9999	-0.44	27	27
PTK2B	0.008	0.032	-9999	-0.5	2	2
PYK2/p130Cas	-0.18	0.12	-9999	-0.49	24	24
ITGAV	0.011	0.003	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.006	0.047	-9999	-0.35	9	9
alphaV/beta3 Integrin/Osteopontin	-0.23	0.16	-9999	-0.32	351	351
MAP3K1	-0.19	0.15	-9999	-0.36	86	86
JUN	0.006	0.046	-9999	-0.5	4	4
MAPK3	-0.18	0.15	-9999	-0.38	85	85
MAPK1	-0.18	0.15	-9999	-0.38	85	85
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0.01	0	-9999	-10000	0	0
MAPK8	-0.17	0.15	-9999	-0.34	86	86
ITGB3	-0.018	0.12	-9999	-0.51	27	27
NFKBIA	-0.16	0.15	-9999	-0.37	85	85
FOS	-0.023	0.13	-9999	-0.5	32	32
CD44	0.002	0.065	-9999	-0.5	8	8
CHUK	0.01	0	-9999	-10000	0	0
PLAU	-0.17	0.18	-9999	-0.51	75	75
NF kappa B1 p50/RelA	-0.16	0.12	-9999	-0.48	21	21
BCAR1	0.009	0.023	-9999	-0.5	1	1
RELA	0.01	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.02	0.083	-9999	-0.36	27	27
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.19	0.15	-9999	-0.36	86	86
VAV3	-0.18	0.15	-9999	-0.52	25	25
MAP3K14	-0.19	0.16	-9999	-0.38	86	86
ROCK2	0.009	0.023	-9999	-0.5	1	1
SPP1	-0.36	0.24	-9999	-0.51	345	345
RAC1	0.01	0	-9999	-10000	0	0
Rac1/GTP	-0.17	0.12	-9999	-0.47	25	25
MMP2	-0.12	0.13	-9999	-0.43	18	18

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.033	0.042	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.085	0.12	-9999	-0.36	31	31
JUN	-0.052	0.12	-9999	-0.35	25	25
HRAS	0.01	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.12	0.16	-9999	-0.3	194	194
RAP1A	0.01	0	-9999	-10000	0	0
FRS2	0.008	0.034	-9999	-0.52	2	2
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.12	0.16	-9999	-0.3	194	194
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.01	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.083	0.13	-9999	-0.27	149	149
RHOA	0.01	0	-9999	-10000	0	0
RAP1A/GTP	-0.1	0.14	-9999	-0.48	25	25
GRB7	0.004	0.057	-9999	-0.51	6	6
RET51/GFRalpha1/GDNF	-0.12	0.16	-9999	-0.3	194	194
MAPKKK cascade	-0.095	0.13	-9999	-0.44	29	29
BCAR1	0.009	0.023	-9999	-0.5	1	1
RET9/GFRalpha1/GDNF/IRS1	-0.084	0.13	-9999	-0.27	149	149
lamellipodium assembly	-0.081	0.11	-9999	-0.34	31	31
RET51/GFRalpha1/GDNF/SHC	-0.12	0.16	-9999	-0.32	136	136
PIK3CA	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.084	0.13	-9999	-0.27	149	149
RET9/GFRalpha1/GDNF/Shank3	-0.087	0.14	-9999	-0.28	150	150
MAPK3	-0.077	0.14	-9999	-0.45	25	25
DOK1	0.01	0	-9999	-10000	0	0
DOK6	-0.039	0.15	-9999	-0.5	47	47
PXN	0.01	0	-9999	-10000	0	0
neurite development	-0.074	0.15	-9999	-0.37	55	55
DOK5	-0.068	0.19	-9999	-0.52	72	72
GFRA1	-0.14	0.23	-9999	-0.5	143	143
MAPK8	-0.059	0.12	-9999	-0.35	24	24
HRAS/GTP	-0.1	0.14	-9999	-0.47	25	25
tube development	-0.08	0.13	-9999	-0.26	150	150
MAPK1	-0.077	0.14	-9999	-0.45	25	25
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.054	0.12	-9999	-0.23	142	142
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
PDLIM7	0.01	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.13	0.18	-9999	-0.52	55	55
SHC1	0.009	0.024	-9999	-0.52	1	1
RET51/GFRalpha1/GDNF/Dok4	-0.12	0.16	-9999	-0.3	194	194
RET51/GFRalpha1/GDNF/Dok5	-0.16	0.18	-9999	-0.32	245	245
PRKCA	0.008	0.032	-9999	-0.5	2	2
HRAS/GDP	0	0	-9999	-10000	0	0
CREB1	-0.07	0.14	-9999	-0.28	142	142
PIK3R1	0.009	0.023	-9999	-0.5	1	1
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.056	0.12	-9999	-0.24	142	142
RET51/GFRalpha1/GDNF/Grb7	-0.12	0.16	-9999	-0.32	139	139
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.062	0.18	-9999	-0.52	67	67
DOK4	0.01	0	-9999	-10000	0	0
JNK cascade	-0.051	0.12	-9999	-0.34	25	25
RET9/GFRalpha1/GDNF/FRS2	-0.084	0.13	-9999	-0.27	151	151
SHANK3	0.002	0.065	-9999	-0.5	8	8
RASA1	0.01	0	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.054	0.12	-9999	-0.23	142	142
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.07	0.13	-9999	-0.37	24	24
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.069	0.13	-9999	-0.27	84	84
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.072	0.14	-9999	-0.42	25	25
PI3K	-0.089	0.19	-9999	-0.52	31	31
SOS1	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.08	0.13	-9999	-0.26	150	150
GRB10	0.01	0	-9999	-10000	0	0
activation of MAPKK activity	-0.064	0.12	-9999	-0.35	23	23
RET51/GFRalpha1/GDNF/FRS2	-0.12	0.16	-9999	-0.32	137	137
GAB1	0.007	0.04	-9999	-0.5	3	3
IRS1	0.009	0.023	-9999	-0.5	1	1
IRS2	0.009	0.023	-9999	-0.5	1	1
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.074	0.14	-9999	-0.44	27	27
RET51/GFRalpha1/GDNF/PKC alpha	-0.12	0.16	-9999	-0.32	136	136
GRB2	0.01	0	-9999	-10000	0	0
PRKACA	0.01	0	-9999	-10000	0	0
GDNF	-0.004	0.071	-9999	-0.52	9	9
RAC1	0.01	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.12	0.16	-9999	-0.36	75	75
Rac1/GTP	-0.095	0.13	-9999	-0.4	31	31
RET9/GFRalpha1/GDNF	-0.094	0.14	-9999	-0.31	149	149
GFRalpha1/GDNF	-0.11	0.17	-9999	-0.36	149	149

×

IL4-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
BCL2L1	-0.46	0.53	-10000	0	-1.2	116	116
STAT6 (cleaved dimer)	-0.49	0.5	-10000	0	-1.2	143	143
IGHG1	-0.15	0.17	-10000	0	-0.38	1	1
IGHG3	-0.45	0.51	-10000	0	-1.2	124	124
AKT1	-0.18	0.24	-10000	0	-0.75	13	13
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.13	0.2	-10000	0	-0.83	9	9
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.19	0.25	-10000	0	-0.88	10	10
THY1	-0.46	0.53	-10000	0	-1.2	117	117
MYB	0.003	0.061	-10000	0	-0.51	7	7
HMGA1	-0.04	0.15	-10000	0	-0.52	46	46
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.24	0.28	-10000	0	-0.63	88	88
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.19	0.25	-10000	0	-0.84	12	12
SP1	0.016	0.004	-10000	0	-10000	0	0
INPP5D	0.007	0.04	-10000	0	-0.5	3	3
SOCS5	0.021	0.014	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.47	0.49	-10000	0	-1.2	124	124
SOCS1	-0.27	0.33	-10000	0	-0.77	89	89
SOCS3	-0.2	0.26	-10000	0	-0.89	15	15
FCER2	-0.35	0.43	-10000	0	-0.99	97	97
PARP14	0.01	0.003	-10000	0	-10000	0	0
CCL17	-0.51	0.6	-10000	0	-1.4	128	128
GRB2	0.01	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.15	0.2	-10000	0	-0.73	8	8
T cell proliferation	-0.44	0.54	-10000	0	-1.2	117	117
IL4R/JAK1	-0.46	0.53	-10000	0	-1.2	117	117
EGR2	-0.48	0.57	-10000	0	-1.3	113	113
JAK2	-0.013	0.045	-10000	0	-0.54	2	2
JAK3	0.015	0.004	-10000	0	-10000	0	0
PIK3R1	0.009	0.023	-10000	0	-0.5	1	1
JAK1	0.006	0.011	-10000	0	-10000	0	0
COL1A2	-0.14	0.19	-10000	0	-0.74	13	13
CCL26	-0.48	0.54	-10000	0	-1.3	115	115
IL4R	-0.49	0.56	-10000	0	-1.3	116	116
PTPN6	0.021	0.013	-10000	0	-10000	0	0
IL13RA2	-0.5	0.58	-10000	0	-1.3	129	129
IL13RA1	-0.011	0.03	-10000	0	-10000	0	0
IRF4	-0.11	0.25	-10000	0	-0.96	26	26
ARG1	-0.12	0.19	-10000	0	-0.71	21	21
CBL	-0.22	0.27	-10000	0	-0.61	74	74
GTF3A	0.005	0.031	-10000	0	-0.51	1	1
PIK3CA	0.01	0	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.015	0.05	-10000	0	-0.4	2	2
IRF4/BCL6	-0.094	0.23	-10000	0	-0.96	22	22
CD40LG	-0.008	0.11	-10000	0	-0.5	22	22
MAPK14	-0.22	0.27	-10000	0	-0.63	60	60
mitosis	-0.17	0.23	-10000	0	-0.7	13	13
STAT6	-0.54	0.63	-10000	0	-1.4	122	122
SPI1	-0.013	0.11	-10000	0	-0.5	25	25
RPS6KB1	-0.16	0.23	-10000	0	-0.72	10	10
STAT6 (dimer)	-0.54	0.63	-10000	0	-1.4	122	122
STAT6 (dimer)/PARP14	-0.49	0.58	-10000	0	-1.3	121	121
mast cell activation	0.01	0.013	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.2	0.26	-10000	0	-0.76	29	29
FRAP1	-0.18	0.24	-10000	0	-0.75	13	13
LTA	-0.46	0.53	-10000	0	-1.2	112	112
FES	0.009	0.023	-10000	0	-0.5	1	1
T-helper 1 cell differentiation	0.52	0.6	1.4	122	-10000	0	122
CCL11	-0.47	0.54	-10000	0	-1.2	124	124
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.18	0.24	-10000	0	-0.79	13	13
IL2RG	0.009	0.051	-10000	0	-0.49	5	5
IL10	-0.46	0.54	-10000	0	-1.3	117	117
IRS1	0.009	0.023	-10000	0	-0.5	1	1
IRS2	0.009	0.023	-10000	0	-0.5	1	1
IL4	-0.099	0.12	-10000	0	-10000	0	0
IL5	-0.46	0.53	-10000	0	-1.2	117	117
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.36	0.4	-10000	0	-0.92	117	117
COL1A1	-0.23	0.24	-10000	0	-0.65	45	45
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.46	0.55	-10000	0	-1.3	107	107
IL2R gamma/JAK3	0.014	0.037	-10000	0	-0.34	5	5
TFF3	-0.51	0.56	-10000	0	-1.3	126	126
ALOX15	-0.79	0.73	-10000	0	-1.4	260	260
MYBL1	-0.002	0.078	-10000	0	-0.52	11	11
T-helper 2 cell differentiation	-0.36	0.41	-10000	0	-0.93	119	119
SHC1	0.009	0.024	-10000	0	-0.52	1	1
CEBPB	0.013	0.006	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.18	0.24	-10000	0	-0.82	11	11
mol:PI-3-4-5-P3	-0.18	0.24	-10000	0	-0.75	13	13
PI3K	-0.18	0.25	-10000	0	-0.81	13	13
DOK2	-0.031	0.14	-10000	0	-0.5	39	39
ETS1	0.019	0.025	-10000	0	-0.46	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.14	0.19	-10000	0	-0.69	8	8
ITGB3	-0.47	0.54	-10000	0	-1.2	120	120
PIGR	-0.6	0.69	-10000	0	-1.5	155	155
IGHE	0.034	0.042	-10000	0	-10000	0	0
MAPKKK cascade	-0.14	0.19	-10000	0	-0.68	8	8
BCL6	0.01	0.003	-10000	0	-10000	0	0
OPRM1	-0.46	0.53	-10000	0	-1.2	117	117
RETNLB	-0.46	0.53	-10000	0	-1.2	113	113
SELP	-0.58	0.68	-10000	0	-1.5	153	153
AICDA	-0.47	0.54	-10000	0	-1.2	125	125

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.022	0.092	-9999	-0.42	22	22
alphaM/beta2 Integrin/GPIbA	-0.027	0.1	-9999	-0.4	29	29
alphaM/beta2 Integrin/proMMP-9	-0.083	0.15	-9999	-0.33	119	119
PLAUR	0.01	0	-9999	-10000	0	0
HMGB1	0.006	0.011	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.022	0.095	-9999	-0.44	21	21
AGER	-0.46	0.15	-9999	-0.51	445	445
RAP1A	0.01	0	-9999	-10000	0	0
SELPLG	-0.009	0.096	-9999	-0.5	18	18
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.29	0.16	-9999	-0.5	125	125
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.097	0.21	-9999	-0.52	99	99
CYR61	-0.017	0.11	-9999	-0.5	26	26
TLN1	0.009	0.023	-9999	-0.5	1	1
Rap1/GTP	-0.083	0.14	-9999	-0.43	45	45
RHOA	0.01	0	-9999	-10000	0	0
P-selectin oligomer	-0.1	0.21	-9999	-0.5	109	109
MYH2	-0.15	0.2	-9999	-0.48	95	95
MST1R	0.008	0.032	-9999	-0.5	2	2
leukocyte activation during inflammatory response	-0.045	0.11	-9999	-0.3	69	69
APOB	-0.043	0.16	-9999	-0.51	49	49
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	0.009	0.024	-9999	-0.52	1	1
JAM3	0.005	0.051	-9999	-0.5	5	5
GP1BA	0	0.069	-9999	-0.5	9	9
alphaM/beta2 Integrin/CTGF	-0.038	0.12	-9999	-0.4	43	43
alphaM/beta2 Integrin	-0.085	0.18	-9999	-0.44	62	62
JAM3 homodimer	0.005	0.051	-9999	-0.5	5	5
ICAM2	0.005	0.051	-9999	-0.5	5	5
ICAM1	0.003	0.06	-9999	-0.5	7	7
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.084	0.18	-9999	-0.44	62	62
cell adhesion	-0.027	0.1	-9999	-0.4	29	29
NFKB1	-0.3	0.22	-9999	-0.62	125	125
THY1	-0.005	0.088	-9999	-0.52	14	14
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.033	0.096	-9999	-0.31	52	52
alphaM/beta2 Integrin/LRP/tPA	-0.051	0.14	-9999	-0.34	67	67
IL6	-0.35	0.33	-9999	-0.85	132	132
ITGB2	-0.005	0.074	-9999	-0.51	10	10
elevation of cytosolic calcium ion concentration	-0.066	0.13	-9999	-0.3	103	103
alphaM/beta2 Integrin/JAM2/JAM3	-0.048	0.14	-9999	-0.36	65	65
JAM2	-0.046	0.16	-9999	-0.5	54	54
alphaM/beta2 Integrin/ICAM1	-0.026	0.1	-9999	-0.5	16	16
alphaM/beta2 Integrin/uPA/Plg	-0.075	0.14	-9999	-0.3	116	116
RhoA/GTP	-0.1	0.19	-9999	-0.49	60	60
positive regulation of phagocytosis	-0.077	0.16	-9999	-0.64	27	27
Ron/MSP	-0.013	0.067	-9999	-0.36	17	17
alphaM/beta2 Integrin/uPAR/uPA	-0.067	0.13	-9999	-0.3	103	103
alphaM/beta2 Integrin/uPAR	-0.021	0.091	-9999	-0.43	21	21
PLAU	-0.087	0.2	-9999	-0.52	90	90
PLAT	-0.052	0.17	-9999	-0.52	57	57
actin filament polymerization	-0.14	0.19	-9999	-0.46	95	95
MST1	-0.006	0.091	-9999	-0.52	15	15
alphaM/beta2 Integrin/lipoprotein(a)	-0.045	0.11	-9999	-0.31	69	69
TNF	-0.28	0.23	-9999	-0.6	125	125
RAP1B	0.01	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.077	0.14	-9999	-0.33	110	110
fibrinolysis	-0.074	0.14	-9999	-0.3	116	116
HCK	-0.012	0.1	-9999	-0.5	21	21
dendritic cell antigen processing and presentation	-0.084	0.18	-9999	-0.44	62	62
VTN	-0.084	0.2	-9999	-0.5	90	90
alphaM/beta2 Integrin/CYR61	-0.037	0.12	-9999	-0.39	43	43
LPA	0	0.04	-9999	-0.51	3	3
LRP1	0.006	0.046	-9999	-0.5	4	4
cell migration	-0.073	0.13	-9999	-0.3	112	112
FN1	0.005	0.052	-9999	-0.5	5	5
alphaM/beta2 Integrin/Thy1	-0.03	0.1	-9999	-0.38	35	35
MPO	-0.003	0.079	-9999	-0.5	12	12
KNG1	-0.03	0.13	-9999	-0.52	32	32
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.09	0.18	-9999	-0.47	55	55
ELA2	0	0	-9999	-10000	0	0
PLG	-0.007	0.07	-9999	-0.52	9	9
CTGF	-0.019	0.12	-9999	-0.5	28	28
alphaM/beta2 Integrin/Hck	-0.033	0.13	-9999	-0.53	28	28
ITGAM	-0.016	0.1	-9999	-0.51	20	20
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.084	0.18	-9999	-0.35	116	116
HP	-0.13	0.23	-9999	-0.5	136	136
leukocyte adhesion	-0.27	0.18	-9999	-0.47	164	164
SELP	-0.1	0.21	-9999	-0.5	109	109

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.078	0.13	-9999	-0.51	18	18
SMAD6-7/SMURF1	-0.043	0.1	-9999	-0.29	72	72
NOG	-0.028	0.13	-9999	-0.5	36	36
SMAD9	-0.12	0.2	-9999	-0.48	108	108
SMAD4	0.01	0	-9999	-10000	0	0
SMAD5	-0.029	0.12	-9999	-0.37	26	26
BMP7/USAG1	-0.27	0.19	-9999	-0.39	346	346
SMAD5/SKI	-0.022	0.11	-9999	-0.43	12	12
SMAD1	0.023	0.029	-9999	-10000	0	0
BMP2	-0.063	0.18	-9999	-0.5	70	70
SMAD1/SMAD1/SMAD4	-0.028	0.068	-9999	-0.41	1	1
BMPR1A	0.01	0	-9999	-10000	0	0
BMPR1B	-0.045	0.16	-9999	-0.5	53	53
BMPR1A-1B/BAMBI	-0.044	0.11	-9999	-0.31	70	70
AHSG	-0.036	0.14	-9999	-0.52	38	38
CER1	-0.004	0.057	-9999	-0.52	6	6
BMP2-4/CER1	-0.055	0.13	-9999	-0.32	83	83
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.021	0.12	-9999	-0.41	23	23
BMP2-4 (homodimer)	-0.061	0.14	-9999	-0.38	79	79
RGMB	0.01	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.067	0.13	-9999	-0.52	18	18
RGMA	-0.001	0.074	-9999	-0.51	10	10
SMURF1	0.01	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.028	0.12	-9999	-0.38	23	23
BMP2-4/USAG1	-0.24	0.18	-9999	-0.34	342	342
SMAD6/SMURF1/SMAD5	-0.022	0.11	-9999	-0.42	13	13
SOSTDC1	-0.33	0.24	-9999	-0.5	324	324
BMP7/BMPR2/BMPR1A-1B	-0.061	0.12	-9999	-0.34	28	28
SKI	0.01	0	-9999	-10000	0	0
BMP6 (homodimer)	-0.067	0.18	-9999	-0.5	74	74
HFE2	-0.007	0.081	-9999	-0.52	12	12
ZFYVE16	0.01	0	-9999	-10000	0	0
MAP3K7	0.01	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.065	0.14	-9999	-0.32	97	97
SMAD5/SMAD5/SMAD4	-0.022	0.11	-9999	-0.43	12	12
MAPK1	0.01	0	-9999	-10000	0	0
TAK1/TAB family	-0.043	0.085	-9999	-0.37	15	15
BMP7 (homodimer)	-0.054	0.17	-9999	-0.5	61	61
NUP214	0.01	0	-9999	-10000	0	0
BMP6/FETUA	-0.082	0.16	-9999	-0.37	107	107
SMAD1/SKI	0.027	0.028	-9999	-10000	0	0
SMAD6	-0.065	0.18	-9999	-0.5	72	72
CTDSP2	0.01	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.074	0.14	-9999	-0.33	111	111
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.35	0.24	-9999	-0.52	335	335
BMPR2 (homodimer)	0.01	0	-9999	-10000	0	0
GADD34/PP1CA	-0.001	0.019	-9999	-0.29	2	2
BMPR1A-1B (homodimer)	-0.038	0.11	-9999	-0.35	53	53
CHRDL1	-0.17	0.24	-9999	-0.5	171	171
ENDOFIN/SMAD1	0.027	0.028	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.033	0.077	-9999	-0.46	1	1
SMAD6/SMURF1	0.01	0	-9999	-10000	0	0
BAMBI	-0.013	0.11	-9999	-0.51	21	21
SMURF2	0.01	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.15	0.2	-9999	-0.37	200	200
BMP2-4/GREM1	-0.26	0.18	-9999	-0.35	357	357
SMAD7	0.009	0.023	-9999	-0.5	1	1
SMAD8A/SMAD8A/SMAD4	-0.093	0.2	-9999	-0.45	108	108
SMAD1/SMAD6	0.027	0.028	-9999	-10000	0	0
TAK1/SMAD6	0	0	-9999	-10000	0	0
BMP7	-0.054	0.17	-9999	-0.5	61	61
BMP6	-0.067	0.18	-9999	-0.5	74	74
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.022	0.11	-9999	-0.36	23	23
PPM1A	0.01	0	-9999	-10000	0	0
SMAD1/SMURF2	0.027	0.028	-9999	-10000	0	0
SMAD7/SMURF1	-0.001	0.016	-9999	-0.35	1	1
CTDSPL	0.01	0	-9999	-10000	0	0
PPP1CA	0.01	0	-9999	-10000	0	0
XIAP	0.01	0	-9999	-10000	0	0
CTDSP1	0.01	0	-9999	-10000	0	0
PPP1R15A	0.008	0.032	-9999	-0.5	2	2
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.043	0.13	-9999	-0.39	36	36
CHRD	-0.015	0.11	-9999	-0.52	23	23
BMPR2	0.01	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.034	0.12	-9999	-0.41	23	23
BMP4	-0.006	0.088	-9999	-0.5	15	15
FST	-0.038	0.15	-9999	-0.51	45	45
BMP2-4/NOG	-0.072	0.15	-9999	-0.35	101	101
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.056	0.11	-9999	-0.49	8	8

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.009	0.024	-9999	-0.52	1	1
LAT2	-0.089	0.2	-9999	-0.48	76	76
AP1	-0.13	0.21	-9999	-0.5	96	96
mol:PIP3	-0.094	0.22	-9999	-0.5	85	85
IKBKB	-0.04	0.12	-9999	-0.27	79	79
AKT1	-0.061	0.16	-9999	-0.38	73	73
IKBKG	-0.04	0.12	-9999	-0.27	79	79
MS4A2	-0.11	0.21	-9999	-0.5	111	111
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.009	0.002	-9999	-10000	0	0
MAP3K1	-0.063	0.18	-9999	-0.4	85	85
mol:Ca2+	-0.066	0.17	-9999	-0.37	85	85
LYN	0.008	0.005	-9999	-10000	0	0
CBLB	-0.084	0.18	-9999	-0.45	74	74
SHC1	0.009	0.024	-9999	-0.52	1	1
RasGAP/p62DOK	-0.027	0.08	-9999	-0.26	50	50
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0.007	0.04	-9999	-0.5	3	3
PLD2	-0.093	0.18	-9999	-0.46	71	71
PTPN13	-0.11	0.22	-9999	-0.5	93	93
PTPN11	0.007	0.008	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.041	0.15	-9999	-0.32	73	73
SYK	0.005	0.042	-9999	-0.53	3	3
GRB2	0.01	0.001	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.13	0.2	-9999	-0.52	85	85
LAT	-0.085	0.19	-9999	-0.45	76	76
PAK2	-0.077	0.2	-9999	-0.46	85	85
NFATC2	-0.069	0.16	-9999	-0.74	20	20
HRAS	-0.092	0.22	-9999	-0.51	85	85
GAB2	0.006	0.046	-9999	-0.5	4	4
PLA2G1B	-0.002	0.031	-9999	-10000	0	0
Fc epsilon R1	-0.15	0.21	-9999	-0.4	177	177
Antigen/IgE/Fc epsilon R1	-0.13	0.2	-9999	-0.36	177	177
mol:GDP	-0.1	0.24	-9999	-0.55	87	87
JUN	0.006	0.046	-9999	-0.5	4	4
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.008	0.023	-9999	-0.5	1	1
FOS	-0.023	0.13	-9999	-0.5	32	32
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.11	0.18	-9999	-0.39	116	116
CHUK	-0.04	0.12	-9999	-0.27	79	79
KLRG1	-0.08	0.18	-9999	-0.42	74	74
VAV1	-0.087	0.19	-9999	-0.46	76	76
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.084	0.18	-9999	-0.45	76	76
negative regulation of mast cell degranulation	-0.071	0.17	-9999	-0.4	74	74
BTK	-0.12	0.26	-9999	-0.6	88	88
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.11	0.22	-9999	-0.41	132	132
GAB2/PI3K/SHP2	-0.1	0.15	-9999	-0.42	73	73
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.095	0.19	-9999	-0.5	71	71
RAF1	0.02	0.023	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.12	0.18	-9999	-0.5	71	71
FCER1G	-0.002	0.087	-9999	-0.51	14	14
FCER1A	-0.13	0.23	-9999	-0.51	128	128
Antigen/IgE/Fc epsilon R1/Fyn	-0.12	0.18	-9999	-0.49	73	73
MAPK3	0.028	0.019	-9999	-10000	0	0
MAPK1	0.028	0.019	-9999	-10000	0	0
NFKB1	0.01	0	-9999	-10000	0	0
MAPK8	-0.01	0.061	-9999	-10000	0	0
DUSP1	-0.042	0.15	-9999	-0.5	50	50
NF-kappa-B/RelA	-0.042	0.061	-9999	-0.23	7	7
actin cytoskeleton reorganization	-0.092	0.2	-9999	-0.49	73	73
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.11	0.18	-9999	-0.45	83	83
FER	-0.084	0.18	-9999	-0.45	75	75
RELA	0.01	0	-9999	-10000	0	0
ITK	-0.037	0.087	-9999	-0.53	12	12
SOS1	0.01	0	-9999	-10000	0	0
PLCG1	-0.1	0.24	-9999	-0.55	85	85
cytokine secretion	-0.031	0.044	-9999	-10000	0	0
SPHK1	-0.086	0.19	-9999	-0.46	75	75
PTK2	-0.096	0.21	-9999	-0.51	73	73
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.14	0.21	-9999	-0.54	86	86
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.09	0.22	-9999	-0.49	86	86
MAP2K2	0.025	0.02	-9999	-10000	0	0
MAP2K1	0.025	0.02	-9999	-10000	0	0
MAP2K7	0.01	0	-9999	-10000	0	0
KLRG1/SHP2	-0.091	0.15	-9999	-0.38	74	74
MAP2K4	0.011	0.011	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.13	0.19	-9999	-0.4	135	135
mol:Choline	-0.092	0.18	-9999	-0.46	71	71
SHC/Grb2/SOS1	-0.098	0.16	-9999	-0.42	73	73
FYN	0.009	0.023	-9999	-0.5	1	1
DOK1	0.01	0	-9999	-10000	0	0
PXN	-0.084	0.19	-9999	-0.47	73	73
HCLS1	-0.086	0.19	-9999	-0.46	76	76
PRKCB	-0.067	0.17	-9999	-0.38	86	86
FCGR2B	0.009	0.023	-9999	-0.5	1	1
IGHE	-0.002	0.006	-9999	-10000	0	0
KLRG1/SHIP	-0.072	0.17	-9999	-0.41	74	74
LCP2	0.006	0.04	-9999	-0.5	3	3
PLA2G4A	-0.12	0.21	-9999	-0.48	96	96
RASA1	0.01	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.092	0.18	-9999	-0.46	71	71
IKK complex	-0.018	0.098	-9999	-0.23	24	24
WIPF1	0.01	0	-9999	-10000	0	0

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.21	0.32	-10000	0	-0.83	51	51
PCK1	-0.18	0.24	-10000	0	-0.66	45	45
HNF4A	-0.39	0.5	-10000	0	-1	146	146
KCNJ11	-0.18	0.33	-10000	0	-0.87	53	53
AKT1	-0.073	0.14	-10000	0	-0.42	6	6
response to starvation	-0.028	0.046	-10000	0	-10000	0	0
DLK1	-0.2	0.32	-10000	0	-0.88	46	46
NKX2-1	-0.11	0.38	-10000	0	-1.3	35	35
ACADM	-0.21	0.32	-10000	0	-0.81	55	55
TAT	-0.17	0.22	-10000	0	-0.59	56	56
CEBPB	0.009	0.005	-10000	0	-10000	0	0
CEBPA	-0.016	0.11	-10000	0	-0.5	25	25
TTR	-0.2	0.25	-10000	0	-0.75	48	48
PKLR	-0.22	0.32	-10000	0	-0.86	51	51
APOA1	-0.49	0.63	-10000	0	-1.3	167	167
CPT1C	-0.22	0.32	-10000	0	-0.87	51	51
ALAS1	-0.073	0.16	-10000	0	-10000	0	0
TFRC	-0.16	0.26	-10000	0	-0.76	30	30
FOXF1	-0.085	0.2	0.22	2	-0.48	93	95
NF1	0.016	0	-10000	0	-10000	0	0
HNF1A (dimer)	-0.12	0.24	-10000	0	-0.57	100	100
CPT1A	-0.21	0.32	-10000	0	-0.81	55	55
HMGCS1	-0.21	0.32	-10000	0	-0.83	51	51
NR3C1	0.004	0.033	-10000	0	-10000	0	0
CPT1B	-0.22	0.32	-10000	0	-0.84	51	51
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	-0.001	0.026	-10000	0	-10000	0	0
GCK	-0.23	0.34	-10000	0	-0.86	63	63
CREB1	0.005	0.021	-10000	0	-10000	0	0
IGFBP1	-0.13	0.2	-10000	0	-0.57	32	32
PDX1	-0.16	0.26	-10000	0	-0.68	56	56
UCP2	-0.21	0.32	-10000	0	-0.83	50	50
ALDOB	-0.2	0.34	-10000	0	-0.86	59	59
AFP	-0.073	0.14	-10000	0	-0.44	31	31
BDH1	-0.21	0.32	-10000	0	-0.84	50	50
HADH	-0.17	0.31	-10000	0	-0.82	48	48
F2	-0.32	0.43	-10000	0	-1	78	78
HNF1A	-0.12	0.24	-10000	0	-0.58	100	100
G6PC	-0.083	0.16	-10000	0	-0.63	12	12
SLC2A2	-0.15	0.24	-10000	0	-0.66	32	32
INS	0.001	0.028	-10000	0	-10000	0	0
FOXA1	-0.015	0.11	0.25	6	-0.54	13	19
FOXA3	-0.17	0.27	-10000	0	-0.58	138	138
FOXA2	-0.21	0.36	-10000	0	-0.9	57	57
ABCC8	-0.24	0.4	-10000	0	-0.94	86	86
ALB	-0.085	0.16	-10000	0	-0.47	37	37

×

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	-0.023	0.12	-10000	0	-0.47	35	35
CDKN2C	0.022	0.032	-10000	0	-0.46	1	1
CDKN2A	-0.15	0.25	-10000	0	-0.53	145	145
CCND2	0.042	0.066	0.2	36	-0.12	5	41
RB1	-0.046	0.069	-10000	0	-0.2	36	36
CDK4	0.05	0.072	0.21	37	-10000	0	37
CDK6	0.047	0.071	0.22	35	-10000	0	35
G1/S progression	0.038	0.074	0.2	36	-10000	0	36

×

Glucocorticoid receptor regulatory network

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
PCK2	0.031	0.086	0.32	6	-10000	0	6
SMARCC2	0.011	0.007	-10000	0	-10000	0	0
SMARCC1	0.011	0.007	-10000	0	-10000	0	0
TBX21	-0.11	0.22	-10000	0	-0.52	75	75
SUMO2	0.009	0.005	-10000	0	-10000	0	0
STAT1 (dimer)	0.017	0	-10000	0	-10000	0	0
FKBP4	0.009	0.024	-10000	0	-0.52	1	1
FKBP5	0.007	0.04	-10000	0	-0.5	3	3
GR alpha/HSP90/FKBP51/HSP90	0.091	0.11	0.29	57	-10000	0	57
PRL	-0.07	0.13	-10000	0	-0.51	9	9
cortisol/GR alpha (dimer)/TIF2	0.21	0.26	0.53	150	-10000	0	150
RELA	-0.033	0.089	-10000	0	-0.3	2	2
FGG	0.004	0.33	0.47	62	-0.46	111	173
GR beta/TIF2	0.096	0.12	0.3	72	-0.25	3	75
IFNG	-0.24	0.28	-10000	0	-0.7	84	84
apoptosis	-0.013	0.15	0.48	9	-0.56	14	23
CREB1	-0.005	0.048	-10000	0	-10000	0	0
histone acetylation	-0.033	0.15	0.27	6	-0.36	38	44
BGLAP	-0.066	0.14	-10000	0	-0.47	13	13
GR/PKAc	0.09	0.1	0.28	54	-10000	0	54
NF kappa B1 p50/RelA	-0.057	0.16	-10000	0	-0.44	29	29
SMARCD1	0.011	0.007	-10000	0	-10000	0	0
MDM2	0.077	0.097	0.25	72	-0.24	1	73
GATA3	0.012	0.041	-10000	0	-0.5	3	3
AKT1	0	0	-10000	0	-10000	0	0
CSF2	-0.12	0.31	-10000	0	-0.98	46	46
GSK3B	0.009	0.005	-10000	0	-10000	0	0
NR1I3	0.011	0.14	0.48	6	-0.56	4	10
CSN2	0.12	0.17	0.39	62	-10000	0	62
BRG1/BAF155/BAF170/BAF60A	0.021	0.029	-10000	0	-0.31	2	2
NFATC1	0.008	0.046	-10000	0	-0.5	4	4
POU2F1	0.01	0.015	-10000	0	-10000	0	0
CDKN1A	0.025	0.061	-10000	0	-1.3	1	1
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0	0.005	-10000	0	-10000	0	0
SFN	0	0.071	-10000	0	-0.52	9	9
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.087	0.11	0.28	54	-10000	0	54
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.021	0.22	0.45	8	-0.8	31	39
JUN	-0.18	0.18	-10000	0	-0.45	100	100
IL4	-0.079	0.15	-10000	0	-0.62	11	11
CDK5R1	-0.007	0.091	-10000	0	-0.52	15	15
PRKACA	0.01	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.13	0.22	0.2	2	-0.46	101	103
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.092	0.1	0.28	53	-10000	0	53
cortisol/GR alpha (monomer)	0.25	0.32	0.63	152	-10000	0	152
NCOA2	0.006	0.046	-10000	0	-0.5	4	4
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.076	0.14	-10000	0	-0.57	32	32
AP-1/NFAT1-c-4	-0.29	0.28	-10000	0	-0.64	149	149
AFP	-0.14	0.17	-10000	0	-0.52	37	37
SUV420H1	0.01	0	-10000	0	-10000	0	0
IRF1	0.13	0.15	0.42	51	-10000	0	51
TP53	0.027	0.023	-10000	0	-0.48	1	1
PPP5C	0.01	0	-10000	0	-10000	0	0
KRT17	-0.27	0.34	-10000	0	-0.76	114	114
KRT14	-0.18	0.2	-10000	0	-0.51	79	79
TBP	0.017	0	-10000	0	-10000	0	0
CREBBP	0.051	0.064	-10000	0	-0.26	2	2
HDAC1	0.008	0.004	-10000	0	-10000	0	0
HDAC2	0.015	0.023	-10000	0	-10000	0	0
AP-1	-0.29	0.28	-10000	0	-0.65	149	149
MAPK14	0.009	0.005	-10000	0	-10000	0	0
MAPK10	-0.047	0.16	-10000	0	-0.5	54	54
MAPK11	0.006	0.04	-10000	0	-0.5	3	3
KRT5	-0.42	0.51	-10000	0	-1.1	162	162
interleukin-1 receptor activity	0.005	0.023	-10000	0	-10000	0	0
NCOA1	0.012	0.001	-10000	0	-10000	0	0
STAT1	0.017	0	-10000	0	-10000	0	0
CGA	-0.11	0.19	-10000	0	-0.55	46	46
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.12	0.19	0.43	88	-10000	0	88
MAPK3	0.009	0.005	-10000	0	-10000	0	0
MAPK1	0.009	0.005	-10000	0	-10000	0	0
ICAM1	-0.14	0.24	-10000	0	-0.64	53	53
NFKB1	-0.033	0.089	-10000	0	-0.27	7	7
MAPK8	-0.15	0.17	-10000	0	-0.42	97	97
MAPK9	0.009	0.005	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.017	0.16	0.48	9	-0.59	14	23
BAX	0.027	0.021	-10000	0	-10000	0	0
POMC	-0.19	0.32	-10000	0	-1.1	33	33
EP300	0.052	0.064	0.22	5	-0.26	2	7
cortisol/GR alpha (dimer)/p53	0.23	0.26	0.55	147	-10000	0	147
proteasomal ubiquitin-dependent protein catabolic process	0.054	0.075	0.22	26	-0.2	1	27
SGK1	0.094	0.11	-10000	0	-1.1	2	2
IL13	-0.16	0.2	-10000	0	-0.6	36	36
IL6	-0.3	0.44	-10000	0	-0.97	132	132
PRKACG	0.002	0.004	-10000	0	-10000	0	0
IL5	-0.15	0.17	-10000	0	-0.55	24	24
IL2	-0.21	0.24	-10000	0	-0.62	72	72
CDK5	0.009	0.003	-10000	0	-10000	0	0
PRKACB	0.009	0.024	-10000	0	-0.52	1	1
HSP90AA1	0.01	0	-10000	0	-10000	0	0
IL8	-0.14	0.23	-10000	0	-0.6	60	60
CDK5R1/CDK5	-0.01	0.064	-10000	0	-0.37	15	15
NF kappa B1 p50/RelA/PKAc	-0.025	0.12	-10000	0	-0.37	16	16
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.21	0.24	0.51	142	-10000	0	142
SMARCA4	0.01	0.024	-10000	0	-0.5	1	1
chromatin remodeling	0.14	0.15	0.37	83	-10000	0	83
NF kappa B1 p50/RelA/Cbp	0.009	0.15	0.32	14	-0.39	17	31
JUN (dimer)	-0.18	0.18	-10000	0	-0.45	101	101
YWHAH	0.01	0	-10000	0	-10000	0	0
VIPR1	-0.36	0.43	-10000	0	-0.85	207	207
NR3C1	0.14	0.19	0.43	98	-10000	0	98
NR4A1	-0.1	0.22	-10000	0	-0.5	109	109
TIF2/SUV420H1	-0.003	0.032	-10000	0	-0.35	4	4
MAPKKK cascade	-0.013	0.15	0.48	9	-0.56	14	23
cortisol/GR alpha (dimer)/Src-1	0.22	0.26	0.55	144	-10000	0	144
PBX1	-0.006	0.089	-10000	0	-0.5	15	15
POU1F1	0.001	0.033	-10000	0	-0.62	1	1
SELE	-0.25	0.43	-10000	0	-1	103	103
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.14	0.15	0.38	81	-10000	0	81
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.21	0.24	0.51	142	-10000	0	142
mol:cortisol	0.13	0.19	0.37	142	-0.21	13	155
MMP1	-0.27	0.2	-10000	0	-0.47	151	151

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.1	0.18	-10000	0	-0.38	145	145
TP53	-0.028	0.046	0.18	1	-10000	0	1
Senescence	-0.028	0.045	0.18	1	-10000	0	1
Apoptosis	-0.028	0.045	0.18	1	-10000	0	1
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.054	0.089	0.19	144	-0.33	2	146
MDM4	0.01	0	-10000	0	-10000	0	0

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.01	0	-9999	-10000	0	0
CCL5	0.005	0.051	-9999	-0.5	5	5
SDCBP	0.01	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.11	0.11	-9999	-0.27	72	72
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.1	0.11	-9999	-0.33	31	31
Syndecan-1/Syntenin	-0.1	0.1	-9999	-0.32	27	27
MAPK3	-0.081	0.097	-9999	-0.5	2	2
HGF/MET	-0.042	0.12	-9999	-0.37	55	55
TGFB1/TGF beta receptor Type II	0.01	0	-9999	-10000	0	0
BSG	0.01	0	-9999	-10000	0	0
keratinocyte migration	-0.1	0.11	-9999	-0.33	31	31
Syndecan-1/RANTES	-0.1	0.11	-9999	-0.33	31	31
Syndecan-1/CD147	-0.091	0.1	-9999	-0.31	28	28
Syndecan-1/Syntenin/PIP2	-0.11	0.088	-9999	-0.31	27	27
LAMA5	0.006	0.046	-9999	-0.5	4	4
positive regulation of cell-cell adhesion	-0.1	0.086	-9999	-0.3	27	27
MMP7	-0.084	0.2	-9999	-0.52	87	87
HGF	-0.018	0.12	-9999	-0.5	27	27
Syndecan-1/CASK	-0.11	0.1	-9999	-0.26	72	72
Syndecan-1/HGF/MET	-0.12	0.14	-9999	-0.38	65	65
regulation of cell adhesion	-0.073	0.095	-9999	-0.48	2	2
HPSE	0.008	0.034	-9999	-0.52	2	2
positive regulation of cell migration	-0.11	0.11	-9999	-0.27	72	72
SDC1	-0.11	0.11	-9999	-0.28	72	72
Syndecan-1/Collagen	-0.11	0.11	-9999	-0.27	72	72
PPIB	0.009	0.024	-9999	-0.52	1	1
MET	-0.023	0.13	-9999	-0.51	31	31
PRKACA	0.01	0	-9999	-10000	0	0
MMP9	-0.097	0.21	-9999	-0.52	99	99
MAPK1	-0.081	0.097	-9999	-0.29	28	28
homophilic cell adhesion	-0.11	0.11	-9999	-0.27	72	72
MMP1	-0.34	0.25	-9999	-0.52	323	323

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.01	0	-9999	-10000	0	0
GNAT1/GTP	-0.007	0.05	-9999	-0.38	9	9
Metarhodopsin II/Arrestin	-0.001	0.014	-9999	-0.32	1	1
PDE6G/GNAT1/GTP	-0.009	0.059	-9999	-0.35	13	13
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	-0.007	0.07	-9999	-0.52	9	9
GRK1	-0.028	0.13	-9999	-0.52	31	31
CNG Channel	-0.1	0.15	-9999	-0.49	38	38
mol:Na +	-0.12	0.16	-9999	-0.5	40	40
mol:ADP	-0.028	0.13	-9999	-0.52	31	31
RGS9-1/Gbeta5/R9AP	-0.13	0.17	-9999	-0.32	201	201
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.12	0.16	-9999	-0.51	40	40
CNGB1	-0.087	0.2	-9999	-0.52	90	90
RDH5	-0.001	0.075	-9999	-0.52	10	10
SAG	0.001	0.024	-9999	-0.52	1	1
mol:Ca2+	-0.093	0.16	-9999	-0.48	40	40
Na + (4 Units)	-0.11	0.14	-9999	-0.46	40	40
RGS9	-0.15	0.24	-9999	-0.5	153	153
GNB1/GNGT1	-0.073	0.15	-9999	-0.37	97	97
GNAT1/GDP	-0.12	0.15	-9999	-0.49	30	30
GUCY2D	0	0.07	-9999	-0.51	9	9
GNGT1	-0.098	0.21	-9999	-0.52	97	97
GUCY2F	0.001	0.024	-9999	-0.52	1	1
GNB5	0.01	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.013	0.094	-9999	-0.42	6	6
mol:11-cis-retinal	-0.001	0.075	-9999	-0.52	10	10
mol:cGMP	-0.051	0.11	-9999	-0.52	5	5
GNB1	0.01	0	-9999	-10000	0	0
Rhodopsin	-0.008	0.053	-9999	-0.37	10	10
SLC24A1	0.01	0	-9999	-10000	0	0
CNGA1	-0.063	0.18	-9999	-0.52	67	67
Metarhodopsin II	-0.018	0.07	-9999	-0.29	31	31
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.055	0.12	-9999	-0.29	92	92
RGS9BP	-0.066	0.18	-9999	-0.5	73	73
Metarhodopsin II/Transducin	-0.021	0.062	-9999	-0.23	3	3
GCAP Family/Ca ++	-0.051	0.11	-9999	-0.3	84	84
PDE6A/B	-0.033	0.1	-9999	-0.35	46	46
mol:Pi	-0.13	0.17	-9999	-0.32	201	201
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.061	0.12	-9999	-0.29	103	103
PDE6B	0.003	0.06	-9999	-0.5	7	7
PDE6A	-0.031	0.14	-9999	-0.5	39	39
PDE6G	0.004	0.057	-9999	-0.5	6	6
RHO	0.004	0.005	-9999	-10000	0	0
PDE6	-0.13	0.16	-9999	-0.48	55	55
GUCA1A	-0.078	0.19	-9999	-0.52	80	80
GC2/GCAP Family	-0.051	0.11	-9999	-0.29	85	85
GUCA1C	0	0.002	-9999	-10000	0	0
GUCA1B	0.001	0.066	-9999	-0.51	8	8

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.002	0.023	-9999	-0.3	3	3
ARNO/beta Arrestin1-2	-0.094	0.11	-9999	-0.35	21	21
EGFR	-0.005	0.086	-9999	-0.51	14	14
EPHA2	-0.001	0.072	-9999	-0.5	10	10
USP6	0.01	0	-9999	-10000	0	0
IQSEC1	0.009	0.023	-9999	-0.5	1	1
EGFR/EGFR/EGF/EGF	-0.079	0.16	-9999	-0.38	103	103
ARRB2	-0.007	0.057	-9999	-0.19	43	43
mol:GTP	0.012	0.021	-9999	-0.13	2	2
ARRB1	0.005	0.051	-9999	-0.5	5	5
FBXO8	0.01	0	-9999	-10000	0	0
TSHR	-0.043	0.16	-9999	-0.52	48	48
EGF	-0.089	0.21	-9999	-0.52	92	92
somatostatin receptor activity	0	0	-9999	-0.001	121	121
ARAP2	-0.008	0.093	-9999	-0.5	17	17
mol:GDP	-0.086	0.12	-9999	-0.26	113	113
mol:PI-3-4-5-P3	0	0	-9999	-0.001	79	79
ITGA2B	-0.043	0.16	-9999	-0.5	50	50
ARF6	0.01	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.006	0.038	-9999	-10000	0	0
ADAP1	0.009	0.023	-9999	-0.5	1	1
KIF13B	0.008	0.032	-9999	-0.5	2	2
HGF/MET	-0.042	0.12	-9999	-0.37	55	55
PXN	0.01	0	-9999	-10000	0	0
ARF6/GTP	-0.082	0.11	-9999	-0.24	111	111
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.066	0.13	-9999	-0.31	103	103
ADRB2	-0.19	0.25	-9999	-0.5	189	189
receptor agonist activity	0	0	-9999	0	125	125
actin filament binding	0	0	-9999	0	121	121
SRC	0.01	0	-9999	-10000	0	0
ITGB3	-0.019	0.12	-9999	-0.51	27	27
GNAQ	0.009	0.023	-9999	-0.5	1	1
EFA6/PI-4-5-P2	0	0	-9999	-0.001	81	81
ARF6/GDP	-0.009	0.074	-9999	-0.37	8	8
ARF6/GDP/GULP/ACAP1	-0.079	0.097	-9999	-0.32	27	27
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.041	0.097	-9999	-0.26	76	76
ACAP1	0.008	0.032	-9999	-0.5	2	2
ACAP2	0.009	0.024	-9999	-0.52	1	1
LHCGR/beta Arrestin2	-0.021	0.079	-9999	-0.28	43	43
EFNA1	0.009	0.023	-9999	-0.5	1	1
HGF	-0.018	0.12	-9999	-0.5	27	27
CYTH3	0.007	0.025	-9999	-0.38	2	2
CYTH2	0.006	0.002	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	0	79	79
endosomal lumen acidification	0	0	-9999	0	35	35
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	0.006	0.046	-9999	-0.5	4	4
GNAQ/ARNO	0.007	0.013	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	35	35
MET	-0.023	0.13	-9999	-0.51	31	31
GNA14	-0.005	0.085	-9999	-0.5	14	14
GNA15	0.01	0	-9999	-10000	0	0
GIT1	0.01	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	107	107
GNA11	0.008	0.033	-9999	-0.5	2	2
LHCGR	-0.041	0.15	-9999	-0.52	43	43
AGTR1	-0.15	0.24	-9999	-0.5	153	153
desensitization of G-protein coupled receptor protein signaling pathway	-0.021	0.079	-9999	-0.28	43	43
IPCEF1/ARNO	-0.044	0.1	-9999	-0.46	3	3
alphaIIb/beta3 Integrin	-0.056	0.13	-9999	-0.36	76	76

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	-0.001	0.022	-10000	0	-0.35	2	2
Necdin/E2F1	-0.01	0.058	-10000	0	-0.36	13	13
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.029	0.079	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/BEX1	-0.12	0.17	-10000	0	-0.33	176	176
NT-4/5 (dimer)/p75(NTR)	-0.03	0.1	-10000	0	-0.37	39	39
IKBKB	0.01	0	-10000	0	-10000	0	0
AKT1	0.002	0.084	-10000	0	-10000	0	0
IKBKG	0.01	0	-10000	0	-10000	0	0
BDNF	-0.25	0.25	-10000	0	-0.5	252	252
MGDIs/NGR/p75(NTR)/LINGO1	-0.049	0.12	-10000	0	-0.31	76	76
FURIN	-0.004	0.085	-10000	0	-0.52	13	13
proBDNF (dimer)/p75(NTR)/Sortilin	-0.16	0.15	-10000	0	-0.3	261	261
LINGO1	-0.057	0.18	-10000	0	-0.52	62	62
Sortilin/TRAF6/NRIF	-0.002	0.02	-10000	0	-10000	0	0
proBDNF (dimer)	-0.25	0.25	-10000	0	-0.5	252	252
NTRK1	-0.011	0.1	-10000	0	-0.5	20	20
RTN4R	0.009	0.023	-10000	0	-0.5	1	1
neuron apoptosis	-0.11	0.14	-10000	0	-0.41	29	29
IRAK1	0.009	0.024	-10000	0	-0.52	1	1
SHC1	-0.013	0.099	-10000	0	-0.3	53	53
ARHGDIA	0.01	0	-10000	0	-10000	0	0
RhoA/GTP	0	0	-10000	0	-10000	0	0
Gamma Secretase	-0.001	0.019	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.029	0.083	-10000	0	-0.26	54	54
MAGEH1	0.01	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.032	0.09	-10000	0	-0.27	58	58
Mammalian IAPs/DIABLO	-0.003	0.029	-10000	0	-0.27	4	4
proNGF (dimer)	-0.028	0.14	-10000	0	-0.51	36	36
MAGED1	0.009	0.024	-10000	0	-0.52	1	1
APP	0.01	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.016	0.11	-10000	0	-0.5	25	25
ZNF274	0.01	0	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.026	0.076	-10000	0	-0.25	52	52
NGF	-0.029	0.14	-10000	0	-0.51	36	36
cell cycle arrest	0.012	0.11	-10000	0	-0.29	22	22
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.008	0.063	-10000	0	-10000	0	0
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.025	0.085	-10000	0	-0.31	39	39
NCSTN	0.01	0	-10000	0	-10000	0	0
mol:GTP	-0.032	0.093	-10000	0	-0.3	53	53
PSENEN	0.009	0.024	-10000	0	-0.52	1	1
mol:ceramide	-0.005	0.09	-10000	0	-0.26	54	54
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.015	0.057	-10000	0	-0.39	1	1
p75(NTR)/beta APP	-0.012	0.064	-10000	0	-0.36	16	16
BEX1	-0.14	0.23	-10000	0	-0.5	144	144
mol:GDP	-0.02	0.098	-10000	0	-0.3	52	52
NGF (dimer)	-0.081	0.13	-10000	0	-0.29	138	138
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.043	0.1	-10000	0	-0.28	76	76
PIK3R1	0.009	0.023	-10000	0	-0.5	1	1
RAC1/GTP	-0.027	0.078	-10000	0	-0.25	52	52
MYD88	0.01	0	-10000	0	-10000	0	0
CHUK	0.01	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.032	0.093	-10000	0	-0.3	53	53
RHOB	0.01	0	-10000	0	-10000	0	0
RHOA	0.01	0	-10000	0	-10000	0	0
MAGE-G1/E2F1	-0.005	0.044	-10000	0	-0.37	7	7
NT3 (dimer)	-0.018	0.12	-10000	0	-0.5	27	27
TP53	-0.1	0.14	-10000	0	-0.46	9	9
PRDM4	-0.005	0.091	-10000	0	-0.26	54	54
BDNF (dimer)	-0.29	0.22	-10000	0	-0.39	368	368
PIK3CA	0.01	0	-10000	0	-10000	0	0
SORT1	0.008	0.032	-10000	0	-0.5	2	2
activation of caspase activity	-0.029	0.078	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.029	0.083	-10000	0	-0.26	54	54
RHOC	0.01	0	-10000	0	-10000	0	0
XIAP	0.01	0	-10000	0	-10000	0	0
MAPK10	-0.096	0.15	-10000	0	-0.41	50	50
DIABLO	0.01	0	-10000	0	-10000	0	0
SMPD2	-0.005	0.091	-10000	0	-0.26	54	54
APH1B	0.008	0.032	-10000	0	-0.5	2	2
APH1A	0.01	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.033	0.093	-10000	0	-0.3	54	54
PSEN1	0.01	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.031	0.11	-10000	0	-0.39	39	39
MAPK8	-0.073	0.12	-10000	0	-0.37	27	27
MAPK9	-0.073	0.12	-10000	0	-0.37	27	27
APAF1	0.01	0	-10000	0	-10000	0	0
NTF3	-0.018	0.12	-10000	0	-0.5	27	27
NTF4	-0.016	0.11	-10000	0	-0.5	25	25
NDN	0.004	0.056	-10000	0	-0.5	6	6
RAC1/GDP	0	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.024	0.068	-10000	0	-10000	0	0
p75 CTF/Sortilin/TRAF6/NRIF	-0.001	0.016	-10000	0	-10000	0	0
RhoA-B-C/GTP	-0.032	0.092	-10000	0	-0.3	53	53
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.13	0.13	-10000	0	-0.49	9	9
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.14	0.14	-10000	0	-0.27	261	261
PRKACB	0.009	0.024	-10000	0	-0.52	1	1
proBDNF (dimer)/p75 ECD	-0.18	0.18	-10000	0	-0.35	252	252
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.004	0.057	-10000	0	-0.51	6	6
BIRC2	0.01	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.019	0.11	0.17	104	-0.27	14	118
BAD	-0.076	0.13	-10000	0	-0.41	23	23
RIPK2	0.01	0	-10000	0	-10000	0	0
NGFR	-0.007	0.092	-10000	0	-0.51	16	16
CYCS	0.001	0.087	-10000	0	-0.5	1	1
ADAM17	0.01	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.028	0.081	-10000	0	-0.26	52	52
BCL2L11	-0.076	0.13	-10000	0	-0.41	23	23
BDNF (dimer)/p75(NTR)	-0.19	0.18	-10000	0	-0.36	261	261
PI3K	-0.029	0.082	-10000	0	-0.27	31	31
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.029	0.083	-10000	0	-0.26	54	54
NDNL2	0.01	0	-10000	0	-10000	0	0
YWHAE	0.01	0	-10000	0	-10000	0	0
PRKCI	0.01	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.038	0.11	-10000	0	-0.36	52	52
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.03	0.085	-10000	0	-0.28	31	31
TRAF6	0.01	0	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCZ	0.007	0.04	-10000	0	-0.5	3	3
PLG	-0.007	0.07	-10000	0	-0.52	9	9
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.13	0.16	-10000	0	-0.47	33	33
SQSTM1	0.009	0.024	-10000	0	-0.52	1	1
NGFRAP1	0.005	0.051	-10000	0	-0.5	5	5
CASP3	-0.07	0.12	-10000	0	-0.38	23	23
E2F1	0.002	0.063	-10000	0	-0.52	7	7
CASP9	0.01	0	-10000	0	-10000	0	0
IKK complex	-0.026	0.068	-10000	0	-0.39	3	3
NGF (dimer)/TRKA	-0.041	0.12	-10000	0	-0.36	55	55
MMP7	-0.084	0.2	-10000	0	-0.52	87	87
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.027	0.076	-10000	0	-10000	0	0
MMP3	-0.2	0.26	-10000	0	-0.52	189	189
APAF-1/Caspase 9	-0.021	0.058	-10000	0	-0.37	2	2

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.003	0.077	-9999	-0.31	29	29
ADCY5	-0.029	0.11	-9999	-0.31	68	68
ADCY6	0.012	0.034	-9999	-0.3	6	6
ADCY7	0.011	0.037	-9999	-0.3	7	7
ADCY1	0.005	0.057	-9999	-0.3	16	16
ADCY2	-0.02	0.1	-9999	-0.31	54	54
ADCY3	0.013	0.032	-9999	-0.3	5	5
ADCY8	-0.12	0.15	-9999	-0.3	204	204
PRKCE	0.005	0.037	-9999	-0.36	5	5
ADCY9	0.006	0.054	-9999	-0.3	15	15
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.062	0.098	-9999	-0.34	27	27

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.004	0.018	-10000	0	-10000	0	0
AES	0.003	0.015	-10000	0	-10000	0	0
FBXW11	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0	0	-10000	0	-10000	0	0
SMAD4	0.01	0	-10000	0	-10000	0	0
DKK2	-0.094	0.2	-10000	0	-0.5	100	100
TLE1	0.003	0.015	-10000	0	-10000	0	0
MACF1	0.006	0.046	-10000	0	-0.5	4	4
CTNNB1	0.088	0.079	0.23	18	-10000	0	18
WIF1	-0.34	0.23	-10000	0	-0.5	339	339
beta catenin/RanBP3	0.011	0.085	0.39	21	-10000	0	21
KREMEN2	-0.13	0.23	-10000	0	-0.52	126	126
DKK1	-0.13	0.23	-10000	0	-0.51	129	129
beta catenin/beta TrCP1	0.089	0.074	0.23	18	-10000	0	18
FZD1	0.01	0.001	-10000	0	-10000	0	0
AXIN2	-0.023	0.23	-10000	0	-1.3	16	16
AXIN1	0.011	0.001	-10000	0	-10000	0	0
RAN	0.009	0.024	-10000	0	-0.52	1	1
Axin1/APC/GSK3/beta catenin	0.008	0.024	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.072	0.061	0.27	1	-10000	0	1
Axin1/APC/GSK3	0.021	0.061	0.2	43	-10000	0	43
Axin1/APC/GSK3/beta catenin/Macf1	0.065	0.045	-10000	0	-10000	0	0
HNF1A	-0.1	0.21	-10000	0	-0.52	100	100
CTBP1	0.003	0.017	-10000	0	-10000	0	0
MYC	0.007	0.1	-10000	0	-1.4	2	2
RANBP3	0.01	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.14	0.19	-10000	0	-0.36	186	186
NKD1	-0.051	0.16	-10000	0	-0.5	58	58
TCF4	0.001	0.036	-10000	0	-0.5	2	2
TCF3	0.003	0.016	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	-0.005	0.038	-10000	0	-0.27	4	4
Ran/GTP	0	0.017	-10000	0	-0.38	1	1
CtBP/CBP/TCF/TLE1/AES	0	0.1	0.44	22	-10000	0	22
LEF1	0.001	0.037	-10000	0	-0.52	2	2
DVL1	0.074	0.052	0.19	1	-0.27	1	2
CSNK2A1	0.01	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.076	0.067	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.16	0.19	-10000	0	-0.35	216	216
LRP6	0.011	0.001	-10000	0	-10000	0	0
CSNK1A1	0.004	0.018	-10000	0	-10000	0	0
NLK	0.01	0.002	-10000	0	-10000	0	0
CCND1	-0.002	0.16	-10000	0	-1.3	6	6
WNT1	-0.001	0.075	-10000	0	-0.52	10	10
GSK3A	0.011	0.001	-10000	0	-10000	0	0
GSK3B	0.01	0.001	-10000	0	-10000	0	0
FRAT1	0.01	0.001	-10000	0	-10000	0	0
PPP2R5D	0.073	0.086	0.3	58	-10000	0	58
APC	0.025	0.04	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.15	0.1	0.22	332	-10000	0	332
CREBBP	0.003	0.016	-10000	0	-10000	0	0

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.004	0.046	-10000	0	-0.5	4	4
GNB1/GNG2	-0.039	0.071	-10000	0	-0.18	94	94
AKT1	-0.003	0.1	-10000	0	-0.19	94	94
EGF	-0.089	0.21	-10000	0	-0.52	92	92
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.012	0.083	-10000	0	-0.41	9	9
mol:Ca2+	-0.022	0.14	-10000	0	-0.3	95	95
LYN	0.029	0.048	-10000	0	-0.37	4	4
RhoA/GTP	-0.026	0.048	-10000	0	-0.13	42	42
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.025	0.16	-10000	0	-0.34	95	95
GNG2	0.008	0.033	-10000	0	-0.5	2	2
ARRB2	0.01	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.024	0.042	-10000	0	-0.33	3	3
G beta5/gamma2	-0.05	0.093	-10000	0	-0.23	94	94
PRKCH	-0.028	0.16	-10000	0	-0.34	95	95
DNM1	0.003	0.058	-10000	0	-0.52	6	6
TXA2/TP beta/beta Arrestin3	-0.003	0.017	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	-0.002	0.076	-10000	0	-0.5	11	11
G12 family/GTP	-0.064	0.12	-10000	0	-0.3	95	95
ADRBK1	0.01	0	-10000	0	-10000	0	0
ADRBK2	0.009	0.023	-10000	0	-0.5	1	1
RhoA/GTP/ROCK1	0	0	-10000	0	-10000	0	0
mol:GDP	0.005	0.095	0.34	10	-10000	0	10
mol:NADP	-0.003	0.08	-10000	0	-0.51	12	12
RAB11A	0.01	0	-10000	0	-10000	0	0
PRKG1	-0.047	0.16	-10000	0	-0.5	55	55
mol:IP3	-0.034	0.18	-10000	0	-0.37	95	95
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	-0.057	0.23	-10000	0	-0.5	95	95
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.009	0.095	-10000	0	-0.37	5	5
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.019	0.072	-10000	0	-0.39	8	8
RHOA	0.01	0	-10000	0	-10000	0	0
PTGIR	0.001	0.069	-10000	0	-0.5	9	9
PRKCB1	-0.034	0.17	-10000	0	-0.37	95	95
GNAQ	0.009	0.023	-10000	0	-0.5	1	1
mol:L-citrulline	-0.003	0.08	-10000	0	-0.51	12	12
TXA2/TXA2-R family	-0.058	0.23	-10000	0	-0.52	95	95
LCK	0.027	0.054	-10000	0	-0.37	6	6
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.009	0.051	-10000	0	-0.5	3	3
TXA2-R family/G12 family/GDP/G beta/gamma	0.022	0.021	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.008	0.049	-10000	0	-0.49	3	3
MAPK14	-0.007	0.11	-10000	0	-0.22	93	93
TGM2/GTP	-0.041	0.19	-10000	0	-0.41	95	95
MAPK11	-0.008	0.11	-10000	0	-0.22	93	93
ARHGEF1	-0.006	0.086	-10000	0	-0.17	93	93
GNAI2	0.01	0	-10000	0	-10000	0	0
JNK cascade	-0.035	0.18	-10000	0	-0.38	95	95
RAB11/GDP	0.01	0.001	-10000	0	-10000	0	0
ICAM1	-0.02	0.14	-10000	0	-0.28	93	93
cAMP biosynthetic process	-0.034	0.16	-10000	0	-0.34	95	95
Gq family/GTP/EBP50	0.015	0.047	-10000	0	-0.34	4	4
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0.029	0.048	-10000	0	-0.37	4	4
GNB5	0.01	0	-10000	0	-10000	0	0
GNB1	0.01	0	-10000	0	-10000	0	0
EGF/EGFR	0.008	0.078	-10000	0	-0.32	13	13
VCAM1	-0.022	0.14	-10000	0	-0.29	93	93
TP beta/Gq family/GDP/G beta5/gamma2	0.024	0.042	-10000	0	-0.33	3	3
platelet activation	-0.01	0.15	-10000	0	-0.29	95	95
PGI2/IP	-0.007	0.048	-10000	0	-0.36	9	9
PRKACA	0.005	0.065	-10000	0	-0.31	17	17
Gq family/GDP/G beta5/gamma2	0.022	0.044	-10000	0	-0.28	6	6
TXA2/TP beta/beta Arrestin2	-0.002	0.014	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.012	0.061	-10000	0	-0.37	7	7
mol:DAG	-0.04	0.19	-10000	0	-0.41	95	95
EGFR	-0.005	0.086	-10000	0	-0.51	14	14
TXA2/TP alpha	-0.051	0.22	-10000	0	-0.47	95	95
Gq family/GTP	-0.007	0.049	-10000	0	-0.24	16	16
YES1	0.029	0.048	-10000	0	-0.37	4	4
GNAI2/GTP	-0.008	0.048	-10000	0	-0.43	4	4
PGD2/DP	-0.008	0.053	-10000	0	-0.36	11	11
SLC9A3R1	0.008	0.034	-10000	0	-0.52	2	2
FYN	0.028	0.049	-10000	0	-0.37	4	4
mol:NO	-0.003	0.08	-10000	0	-0.51	12	12
GNA15	0.01	0	-10000	0	-10000	0	0
PGK/cGMP	-0.041	0.11	-10000	0	-0.31	65	65
RhoA/GDP	0.01	0.001	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.011	0.056	-10000	0	-0.46	5	5
NOS3	-0.003	0.08	-10000	0	-0.51	12	12
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCA	-0.028	0.16	-10000	0	-0.34	96	96
PRKCB	-0.03	0.17	-10000	0	-0.35	97	97
PRKCE	-0.027	0.16	-10000	0	-0.34	96	96
PRKCD	-0.033	0.17	-10000	0	-0.37	95	95
PRKCG	-0.044	0.18	-10000	0	-0.39	95	95
muscle contraction	-0.051	0.22	-10000	0	-0.48	95	95
PRKCZ	-0.026	0.16	-10000	0	-0.34	95	95
ARR3	0	0.033	-10000	0	-0.52	2	2
TXA2/TP beta	-0.009	0.053	-10000	0	-0.48	4	4
PRKCQ	-0.05	0.18	-10000	0	-0.38	97	97
MAPKKK cascade	-0.049	0.21	-10000	0	-0.45	95	95
SELE	-0.042	0.18	-10000	0	-0.39	95	95
TP beta/GNAI2/GDP/G beta/gamma	-0.009	0.052	-10000	0	-0.47	4	4
ROCK1	0.01	0	-10000	0	-10000	0	0
GNA14	-0.005	0.085	-10000	0	-0.5	14	14
chemotaxis	-0.072	0.26	-10000	0	-0.59	95	95
GNA12	0.01	0	-10000	0	-10000	0	0
GNA13	0.01	0	-10000	0	-10000	0	0
GNA11	0.008	0.032	-10000	0	-0.5	2	2
Rac1/GTP	0	0	-10000	0	-10000	0	0

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.043	0.11	-10000	0	-0.31	68	68
fibroblast growth factor receptor signaling pathway	-0.043	0.11	-10000	0	-0.31	68	68
LAMA1	-0.018	0.12	-10000	0	-0.51	26	26
PRNP	0.007	0.04	-10000	0	-0.5	3	3
GPC1/SLIT2	-0.089	0.15	-10000	0	-0.35	123	123
SMAD2	0.019	0.046	-10000	0	-0.27	1	1
GPC1/PrPc/Cu2+	-0.004	0.033	-10000	0	-0.3	6	6
GPC1/Laminin alpha1	-0.021	0.088	-10000	0	-0.37	28	28
TDGF1	-0.02	0.12	-10000	0	-0.51	27	27
CRIPTO/GPC1	-0.022	0.087	-10000	0	-0.36	30	30
APP/GPC1	-0.002	0.027	-10000	0	-0.35	3	3
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0.002	0.077	-10000	0	-0.3	30	30
FLT1	0.01	0	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	-0.008	0.047	-10000	0	-0.29	13	13
SERPINC1	-0.002	0.071	-10000	0	-0.52	9	9
FYN	0.001	0.08	-10000	0	-0.31	30	30
FGR	-0.022	0.12	-10000	0	-0.32	62	62
positive regulation of MAPKKK cascade	-0.017	0.12	-10000	0	-0.37	33	33
SLIT2	-0.12	0.22	-10000	0	-0.5	121	121
GPC1/NRG	-0.075	0.15	-10000	0	-0.36	102	102
NRG1	-0.095	0.21	-10000	0	-0.5	101	101
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.002	0.023	-10000	0	-0.29	3	3
LYN	0.002	0.077	-10000	0	-0.3	30	30
mol:Spermine	0.007	0.029	-10000	0	-0.36	3	3
cell growth	-0.043	0.11	-10000	0	-0.31	68	68
BMP signaling pathway	-0.007	0.04	0.5	3	-10000	0	3
SRC	0.002	0.077	-10000	0	-0.3	30	30
TGFBR1	0.009	0.024	-10000	0	-0.52	1	1
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.075	0.19	-10000	0	-0.5	81	81
GPC1	0.007	0.04	-10000	0	-0.5	3	3
TGFBR1 (dimer)	0.009	0.024	-10000	0	-0.52	1	1
VEGFA	0.01	0	-10000	0	-10000	0	0
BLK	-0.051	0.14	-10000	0	-0.31	106	106
HCK	-0.012	0.1	-10000	0	-0.31	48	48
FGF2	-0.059	0.17	-10000	0	-0.5	66	66
FGFR1	0.007	0.04	-10000	0	-0.5	3	3
VEGFR1 homodimer	0.01	0	-10000	0	-10000	0	0
TGFBR2	0.001	0.068	-10000	0	-0.5	9	9
cell death	-0.002	0.027	-10000	0	-0.35	3	3
ATIII/GPC1	-0.009	0.056	-10000	0	-0.36	12	12
PLA2G2A/GPC1	-0.061	0.14	-10000	0	-0.36	83	83
LCK	0	0.08	-10000	0	-0.3	33	33
neuron differentiation	-0.075	0.15	-10000	0	-0.36	102	102
PrPc/Cu2+	-0.002	0.028	-10000	0	-0.36	3	3
APP	0.01	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.001	0.068	-10000	0	-0.5	9	9

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	-0.09	0.17	-9999	-0.38	126	126
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.039	0.11	-9999	-0.36	54	54
STXBP1	0.007	0.04	-9999	-0.5	3	3
ACh/CHRNA1	-0.034	0.099	-9999	-0.34	42	42
RAB3GAP2/RIMS1/UNC13B	-0.033	0.093	-9999	-0.3	54	54
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	-0.048	0.16	-9999	-0.5	54	54
mol:ACh	-0.016	0.04	-9999	-0.079	129	129
RAB3GAP2	0.01	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.081	0.11	-9999	-0.36	24	24
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.033	0.099	-9999	-0.34	42	42
UNC13B	0.01	0	-9999	-10000	0	0
CHRNA1	-0.034	0.14	-9999	-0.51	41	41
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.036	0.11	-9999	-0.36	45	45
SNAP25	-0.002	0.039	-9999	-0.18	21	21
VAMP2	0.005	0	-9999	-10000	0	0
SYT1	-0.038	0.15	-9999	-0.51	45	45
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.072	0.14	-9999	-0.31	129	129
STX1A/SNAP25 fragment 1/VAMP2	-0.081	0.11	-9999	-0.36	24	24

×

Ephrin B reverse signaling

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.002	0.065	-10000	0	-0.5	8	8
EPHB2	-0.047	0.16	-10000	0	-0.52	53	53
EFNB1	0.011	0.051	-10000	0	-0.36	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.058	0.12	-10000	0	-0.5	15	15
Ephrin B2/EPHB1-2	-0.06	0.13	-10000	0	-0.3	107	107
neuron projection morphogenesis	-0.055	0.11	-10000	0	-0.47	15	15
Ephrin B1/EPHB1-2/Tiam1	-0.058	0.13	-10000	0	-0.49	18	18
DNM1	0.003	0.058	-10000	0	-0.52	6	6
cell-cell signaling	0.001	0.002	-10000	0	-10000	0	0
MAP2K4	-0.045	0.18	-10000	0	-0.58	50	50
YES1	-0.081	0.24	-10000	0	-0.81	50	50
Ephrin B1/EPHB1-2/NCK2	-0.054	0.12	-10000	0	-0.4	22	22
PI3K	-0.046	0.18	-10000	0	-0.59	50	50
mol:GDP	-0.058	0.13	-10000	0	-0.42	24	24
ITGA2B	-0.043	0.16	-10000	0	-0.5	50	50
endothelial cell proliferation	-0.005	0.038	-10000	0	-0.3	8	8
FYN	-0.082	0.24	-10000	0	-0.81	50	50
MAP3K7	-0.063	0.19	-10000	0	-0.62	50	50
FGR	-0.093	0.25	-10000	0	-0.82	50	50
TIAM1	0.002	0.065	-10000	0	-0.5	8	8
PIK3R1	0.009	0.023	-10000	0	-0.5	1	1
RGS3	0.01	0	-10000	0	-10000	0	0
cell adhesion	-0.07	0.2	-10000	0	-0.58	50	50
LYN	-0.081	0.24	-10000	0	-0.81	50	50
Ephrin B1/EPHB1-2/Src Family Kinases	-0.076	0.23	-10000	0	-0.74	50	50
Ephrin B1/EPHB1-2	-0.071	0.2	-10000	0	-0.67	50	50
SRC	-0.081	0.24	-10000	0	-0.8	50	50
ITGB3	-0.019	0.12	-10000	0	-0.51	27	27
EPHB1	-0.051	0.17	-10000	0	-0.52	56	56
EPHB4	0.01	0	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	-0.005	0.038	-10000	0	-0.3	8	8
alphaIIb/beta3 Integrin	-0.056	0.13	-10000	0	-0.36	76	76
BLK	-0.087	0.24	-10000	0	-0.81	50	50
HCK	-0.087	0.25	-10000	0	-0.82	50	50
regulation of stress fiber formation	0.054	0.12	0.4	22	-10000	0	22
MAPK8	-0.037	0.17	-10000	0	-0.55	50	50
Ephrin B1/EPHB1-2/RGS3	-0.054	0.12	-10000	0	-0.4	22	22
endothelial cell migration	-0.055	0.17	-10000	0	-0.53	51	51
NCK2	0.01	0	-10000	0	-10000	0	0
PTPN13	-0.057	0.19	-10000	0	-0.61	50	50
regulation of focal adhesion formation	0.054	0.12	0.4	22	-10000	0	22
chemotaxis	0.054	0.12	0.4	22	-10000	0	22
PIK3CA	0.01	0	-10000	0	-10000	0	0
Rac1/GTP	-0.057	0.12	-10000	0	-0.49	15	15
angiogenesis	-0.071	0.2	-10000	0	-0.67	50	50
LCK	-0.082	0.24	-10000	0	-0.8	50	50

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	-0.009	0.054	-9999	-0.35	12	12
alphaV beta3 Integrin	-0.056	0.12	-9999	-0.31	89	89
PTK2	-0.056	0.15	-9999	-0.44	36	36
IGF1R	0.008	0.032	-9999	-0.5	2	2
PI4KB	0.01	0	-9999	-10000	0	0
MFGE8	0.01	0	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
CDKN1B	-0.1	0.2	-9999	-0.5	84	84
VEGFA	0.01	0	-9999	-10000	0	0
ILK	-0.1	0.2	-9999	-0.5	84	84
ROCK1	0.01	0	-9999	-10000	0	0
AKT1	-0.094	0.18	-9999	-0.46	84	84
PTK2B	0.009	0.079	-9999	-0.48	2	2
alphaV/beta3 Integrin/JAM-A	-0.09	0.15	-9999	-0.51	29	29
CBL	0.01	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.032	0.094	-9999	-0.3	52	52
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.007	0.046	-9999	-0.52	1	1
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.017	0.097	-9999	-0.37	9	9
alphaV/beta3 Integrin/Syndecan-1	-0.017	0.069	-9999	-0.3	27	27
PI4KA	0.01	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.049	0.11	-9999	-0.53	11	11
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.23	0.16	-9999	-0.32	351	351
RPS6KB1	-0.009	0.12	-9999	-0.49	11	11
TLN1	0.009	0.023	-9999	-0.5	1	1
MAPK3	-0.093	0.19	-9999	-0.51	69	69
GPR124	0.007	0.04	-9999	-0.5	3	3
MAPK1	-0.093	0.19	-9999	-0.51	69	69
PXN	0.01	0	-9999	-10000	0	0
PIK3R1	0.009	0.023	-9999	-0.5	1	1
alphaV/beta3 Integrin/Tumstatin	-0.097	0.14	-9999	-0.3	156	156
cell adhesion	-0.025	0.07	-9999	-0.28	5	5
ANGPTL3	-0.021	0.12	-9999	-0.52	25	25
VEGFR2 homodimer/VEGFA homodimer/Src	-0.007	0.045	-9999	-0.29	12	12
IGF-1R heterotetramer	0.008	0.032	-9999	-0.5	2	2
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	0.001	0.068	-9999	-0.5	9	9
ITGB3	-0.019	0.12	-9999	-0.51	27	27
IGF1	-0.002	0.076	-9999	-0.5	11	11
RAC1	0.01	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.018	0.076	-9999	-0.32	28	28
apoptosis	0.01	0	-9999	-10000	0	0
CD47	0.008	0.032	-9999	-0.5	2	2
alphaV/beta3 Integrin/CD47	-0.018	0.071	-9999	-0.3	29	29
VCL	0.01	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.041	0.11	-9999	-0.32	63	63
CSF1	0.005	0.051	-9999	-0.5	5	5
PIK3C2A	-0.1	0.2	-9999	-0.5	84	84
PI4 Kinase/Pyk2	-0.078	0.13	-9999	-0.44	32	32
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.021	0.074	-9999	-0.27	38	38
FAK1/Vinculin	-0.04	0.12	-9999	-0.34	36	36
alphaV beta3/Integrin/ppsTEM5	-0.018	0.076	-9999	-0.32	28	28
RHOA	0.01	0	-9999	-10000	0	0
VTN	-0.084	0.2	-9999	-0.5	90	90
BCAR1	0.009	0.023	-9999	-0.5	1	1
FGF2	-0.059	0.17	-9999	-0.5	66	66
F11R	-0.033	0.13	-9999	-0.35	67	67
alphaV/beta3 Integrin/Lactadherin	-0.017	0.069	-9999	-0.3	27	27
alphaV/beta3 Integrin/TGFBR2	-0.022	0.078	-9999	-0.3	36	36
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.003	0.028	-9999	-0.26	6	6
HSP90AA1	0.01	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.016	0.066	-9999	-0.28	27	27
mol:GDP	0	0	-9999	-10000	0	0
FN1	0.005	0.052	-9999	-0.5	5	5
alphaV/beta3 Integrin/Pyk2	-0.02	0.071	-9999	-0.48	2	2
SDC1	0.01	0	-9999	-10000	0	0
VAV3	0.025	0.045	-9999	-0.49	1	1
PTPN11	0.01	0	-9999	-10000	0	0
IRS1	0.009	0.023	-9999	-0.5	1	1
FAK1/Paxillin	-0.04	0.12	-9999	-0.34	36	36
cell migration	-0.03	0.12	-9999	-0.36	16	16
ITGAV	0.01	0	-9999	-10000	0	0
PI3K	-0.08	0.13	-9999	-0.46	29	29
SPP1	-0.36	0.24	-9999	-0.52	345	345
KDR	-0.003	0.079	-9999	-0.5	12	12
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.01	0	-9999	-10000	0	0
COL4A3	-0.13	0.23	-9999	-0.5	135	135
angiogenesis	-0.072	0.21	-9999	-0.51	71	71
Rac1/GTP	-0.005	0.036	-9999	-0.44	1	1
EDIL3	-0.033	0.14	-9999	-0.5	41	41
cell proliferation	-0.022	0.078	-9999	-0.3	36	36

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.01	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.038	0.075	-10000	0	-0.28	18	18
NT3 (dimer)/TRKC	-0.087	0.17	-10000	0	-0.39	110	110
NT3 (dimer)/TRKB	-0.13	0.17	-10000	0	-0.32	200	200
SHC/Grb2/SOS1/GAB1/PI3K	0.027	0.024	-10000	0	-10000	0	0
RAPGEF1	0.01	0	-10000	0	-10000	0	0
BDNF	-0.25	0.25	-10000	0	-0.5	252	252
PIK3CA	0.01	0	-10000	0	-10000	0	0
DYNLT1	0.01	0	-10000	0	-10000	0	0
NTRK1	-0.011	0.1	-10000	0	-0.5	20	20
NTRK2	-0.18	0.24	-10000	0	-0.5	179	179
NTRK3	-0.09	0.2	-10000	0	-0.5	96	96
NT-4/5 (dimer)/TRKB	-0.13	0.17	-10000	0	-0.32	196	196
neuron apoptosis	0.2	0.19	0.52	104	-10000	0	104
SHC 2-3/Grb2	-0.21	0.22	-10000	0	-0.57	104	104
SHC1	0.009	0.024	-10000	0	-0.52	1	1
SHC2	-0.14	0.14	-10000	0	-0.47	44	44
SHC3	-0.22	0.26	-10000	0	-0.64	112	112
STAT3 (dimer)	0.012	0.038	-10000	0	-0.32	6	6
NT3 (dimer)/TRKA	-0.038	0.11	-10000	0	-0.32	58	58
RIN/GDP	-0.024	0.075	-10000	0	-0.27	5	5
GIPC1	0.01	0	-10000	0	-10000	0	0
KRAS	0.009	0.024	-10000	0	-0.52	1	1
DNAJA3	-0.027	0.07	-10000	0	-0.31	10	10
RIN/GTP	-0.002	0.029	-10000	0	-0.38	3	3
CCND1	0.015	0.083	-10000	0	-0.73	6	6
MAGED1	0.009	0.024	-10000	0	-0.52	1	1
PTPN11	0.01	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.016	0.11	-10000	0	-0.5	25	25
SHC/GRB2/SOS1	-0.001	0.014	-10000	0	-0.3	1	1
GRB2	0.01	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.046	0.12	-10000	0	-0.33	68	68
TRKA/NEDD4-2	-0.014	0.07	-10000	0	-0.35	20	20
ELMO1	0.005	0.052	-10000	0	-0.5	5	5
RhoG/GTP/ELMO1/DOCK1	-0.003	0.03	-10000	0	-0.3	5	5
NGF	-0.029	0.14	-10000	0	-0.51	36	36
HRAS	0.01	0	-10000	0	-10000	0	0
DOCK1	0.01	0	-10000	0	-10000	0	0
GAB2	0.006	0.046	-10000	0	-0.5	4	4
RIT2	-0.002	0.041	-10000	0	-0.52	3	3
RIT1	0.01	0	-10000	0	-10000	0	0
FRS2	0.008	0.034	-10000	0	-0.52	2	2
DNM1	0.003	0.058	-10000	0	-0.52	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.01	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.028	0.075	-10000	0	-0.32	14	14
mol:GDP	-0.034	0.1	-10000	0	-0.32	11	11
NGF (dimer)	-0.028	0.14	-10000	0	-0.51	36	36
RhoG/GDP	-0.004	0.036	-10000	0	-0.36	5	5
RIT1/GDP	-0.019	0.074	-10000	0	-0.24	3	3
TIAM1	0.002	0.065	-10000	0	-0.5	8	8
PIK3R1	0.009	0.023	-10000	0	-0.5	1	1
BDNF (dimer)/TRKB	-0.25	0.21	-10000	0	-0.38	328	328
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	-0.001	0.017	-10000	0	-0.37	1	1
FRS2 family/SHP2	-0.001	0.019	-10000	0	-0.3	2	2
SHC/GRB2/SOS1/GAB1	-0.002	0.023	-10000	0	-0.27	1	1
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.018	0.12	-10000	0	-0.5	27	27
RAP1/GDP	-0.031	0.051	-10000	0	-0.24	1	1
KIDINS220/CRKL	0.01	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.25	0.25	-10000	0	-0.5	252	252
ubiquitin-dependent protein catabolic process	-0.034	0.096	-10000	0	-0.3	55	55
Schwann cell development	-0.047	0.034	-10000	0	-10000	0	0
EHD4	0.01	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	-0.001	0.017	-10000	0	-0.27	2	2
FRS2 family/SHP2/CRK family/C3G/GAB2	0.03	0.021	-10000	0	-10000	0	0
RAP1B	0.01	0	-10000	0	-10000	0	0
RAP1A	0.01	0	-10000	0	-10000	0	0
CDC42/GTP	-0.24	0.21	-10000	0	-0.5	166	166
ABL1	0.01	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
Rap1/GTP	-0.091	0.074	-10000	0	-0.28	1	1
STAT3	0.012	0.038	-10000	0	-0.32	6	6
axon guidance	-0.23	0.2	-10000	0	-0.48	166	166
MAPK3	-0.018	0.12	-10000	0	-0.3	68	68
MAPK1	-0.018	0.12	-10000	0	-0.3	68	68
CDC42/GDP	-0.019	0.074	-10000	0	-0.24	3	3
NTF3	-0.018	0.12	-10000	0	-0.5	27	27
NTF4	-0.016	0.11	-10000	0	-0.5	25	25
NGF (dimer)/TRKA/FAIM	-0.034	0.096	-10000	0	-0.3	55	55
PI3K	-0.001	0.016	-10000	0	-0.35	1	1
FRS3	0.01	0	-10000	0	-10000	0	0
FAIM	0.01	0	-10000	0	-10000	0	0
GAB1	0.007	0.04	-10000	0	-0.5	3	3
RASGRF1	-0.12	0.14	-10000	0	-0.27	209	209
SOS1	0.01	0	-10000	0	-10000	0	0
MCF2L	-0.058	0.15	-10000	0	-0.32	113	113
RGS19	0.01	0	-10000	0	-10000	0	0
CDC42	0.01	0	-10000	0	-10000	0	0
RAS family/GTP	-0.009	0.064	-10000	0	-10000	0	0
Rac1/GDP	-0.019	0.074	-10000	0	-0.24	3	3
NGF (dimer)/TRKA/GRIT	-0.035	0.098	-10000	0	-0.31	55	55
neuron projection morphogenesis	-0.001	0.08	-10000	0	-0.45	2	2
NGF (dimer)/TRKA/NEDD4-2	-0.034	0.096	-10000	0	-0.3	55	55
MAP2K1	0.029	0.024	-10000	0	-10000	0	0
NGFR	-0.007	0.092	-10000	0	-0.51	16	16
NGF (dimer)/TRKA/GIPC/GAIP	0.004	0.071	-10000	0	-0.36	1	1
RAS family/GTP/PI3K	0.024	0.013	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	-0.001	0.016	-10000	0	-10000	0	0
NRAS	0.01	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
PRKCI	0.01	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCZ	0.007	0.04	-10000	0	-0.5	3	3
MAPKKK cascade	-0.085	0.16	-10000	0	-0.65	33	33
RASA1	0.01	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.014	0.07	-10000	0	-0.35	20	20
SQSTM1	0.009	0.024	-10000	0	-0.52	1	1
BDNF (dimer)/TRKB/GIPC	-0.23	0.19	-10000	0	-0.52	103	103
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.03	0.082	-10000	0	-0.49	2	2
MATK	-0.012	0.1	-10000	0	-0.5	21	21
NEDD4L	0.01	0	-10000	0	-10000	0	0
RAS family/GDP	-0.026	0.048	-10000	0	-0.22	1	1
NGF (dimer)/TRKA	-0.029	0.076	-10000	0	-0.25	40	40
Rac1/GTP	-0.086	0.097	-10000	0	-0.29	46	46
FRS2 family/SHP2/CRK family	-0.001	0.016	-10000	0	-10000	0	0

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.01	0	-9999	-10000	0	0
EGFR	-0.005	0.086	-9999	-0.51	14	14
EGF/EGFR	-0.088	0.14	-9999	-0.28	156	156
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.054	0.11	-9999	-0.5	3	3
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.008	0.032	-9999	-0.5	2	2
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.089	0.21	-9999	-0.52	92	92
EGF/EGFR dimer/SHC	-0.066	0.13	-9999	-0.31	104	104
mol:GDP	-0.054	0.1	-9999	-0.49	3	3
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.065	0.18	-9999	-0.5	72	72
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.048	0.095	-9999	-0.46	3	3
SHC1	0.009	0.024	-9999	-0.52	1	1
HRAS/GDP	-0.05	0.097	-9999	-0.46	3	3
FRAP1	-0.028	0.11	-9999	-0.48	3	3
EGF/EGFR dimer	-0.079	0.16	-9999	-0.38	103	103
SOS1	0.01	0	-9999	-10000	0	0
GRB2	0.01	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.053	0.13	-9999	-0.35	74	74

×

ErbB4 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
ErbB4/ErbB4/HBEGF/HBEGF	-0.074	0.14	-10000	0	-0.41	42	42
epithelial cell differentiation	-0.077	0.12	-10000	0	-0.43	24	24
ITCH	0.023	0.018	-10000	0	-10000	0	0
WWP1	-0.02	0.068	-10000	0	-10000	0	0
FYN	0.009	0.023	-10000	0	-0.5	1	1
EGFR	-0.005	0.086	-10000	0	-0.51	14	14
PRL	-0.01	0.084	-10000	0	-0.52	13	13
neuron projection morphogenesis	-0.027	0.11	-10000	0	-0.44	2	2
PTPRZ1	-0.11	0.22	-10000	0	-0.51	114	114
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.067	0.1	-10000	0	-0.49	2	2
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.068	0.14	-10000	0	-0.36	51	51
ADAM17	0.023	0.018	-10000	0	-10000	0	0
ErbB4/ErbB4	-0.034	0.089	-10000	0	-0.38	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.14	0.17	-10000	0	-0.41	85	85
NCOR1	0.01	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.077	0.12	-10000	0	-0.34	51	51
GRIN2B	-0.059	0.13	-10000	0	-0.5	5	5
ErbB4/ErbB2/betacellulin	-0.033	0.061	-10000	0	-0.34	11	11
STAT1	0.01	0	-10000	0	-10000	0	0
HBEGF	-0.077	0.19	-10000	0	-0.5	83	83
PRLR	-0.054	0.17	-10000	0	-0.51	60	60
E4ICDs/ETO2	-0.043	0.11	-10000	0	-0.42	18	18
axon guidance	0.002	0.076	-10000	0	-10000	0	0
NEDD4	0.022	0.029	-10000	0	-0.47	1	1
Prolactin receptor/Prolactin receptor/Prolactin	-0.055	0.13	-10000	0	-0.38	71	71
CBFA2T3	-0.023	0.13	-10000	0	-0.5	32	32
ErbB4/ErbB2/HBEGF	-0.069	0.11	-10000	0	-0.34	44	44
MAPK3	-0.034	0.12	-10000	0	-0.46	2	2
STAT1 (dimer)	-0.025	0.074	-10000	0	-0.32	1	1
MAPK1	-0.034	0.12	-10000	0	-0.46	2	2
JAK2	0.008	0.032	-10000	0	-0.5	2	2
ErbB4/ErbB2/neuregulin 1 beta	-0.078	0.12	-10000	0	-0.34	54	54
NRG1	-0.052	0.15	-10000	0	-0.35	101	101
NRG3	-0.19	0.25	-10000	0	-0.5	192	192
NRG2	-0.048	0.16	-10000	0	-0.5	55	55
NRG4	-0.036	0.15	-10000	0	-0.51	42	42
heart development	0.002	0.076	-10000	0	-10000	0	0
neural crest cell migration	-0.059	0.13	-10000	0	-0.34	54	54
ERBB2	0.024	0.032	-10000	0	-0.36	3	3
WWOX/E4ICDs	-0.025	0.074	-10000	0	-0.32	1	1
SHC1	0.009	0.024	-10000	0	-0.52	1	1
ErbB4/EGFR/neuregulin 4	-0.068	0.11	-10000	0	-0.4	27	27
apoptosis	0.21	0.23	0.45	191	-10000	0	191
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.058	0.12	-10000	0	-0.4	31	31
ErbB4/ErbB2/epiregulin	-0.11	0.13	-10000	0	-0.34	70	70
ErbB4/ErbB4/betacellulin/betacellulin	-0.032	0.091	-10000	0	-0.4	10	10
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.11	0.15	-10000	0	-0.4	76	76
MDM2	-0.023	0.078	-10000	0	-0.32	1	1
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.07	0.11	-10000	0	-0.32	51	51
STAT5A	0.007	0.072	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.084	0.12	-10000	0	-0.36	55	55
DLG4	0.01	0	-10000	0	-10000	0	0
GRB2/SHC	-0.001	0.017	-10000	0	-0.37	1	1
E4ICDs/TAB2/NCoR1	-0.04	0.055	-10000	0	-0.3	1	1
STAT5A (dimer)	-0.082	0.13	-10000	0	-0.47	24	24
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.006	0.069	-10000	0	-10000	0	0
LRIG1	0.008	0.032	-10000	0	-0.5	2	2
EREG	-0.15	0.24	-10000	0	-0.51	154	154
BTC	-0.003	0.079	-10000	0	-0.5	12	12
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.001	0.074	-10000	0	-10000	0	0
ERBB4	-0.034	0.089	-10000	0	-0.38	1	1
STAT5B	0.01	0	-10000	0	-10000	0	0
YAP1	-0.001	0.024	-10000	0	-0.53	1	1
GRB2	0.01	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.049	0.086	-10000	0	-0.34	22	22
glial cell differentiation	0.04	0.055	0.3	1	-10000	0	1
WWOX	0.01	0	-10000	0	-10000	0	0
cell proliferation	-0.067	0.15	-10000	0	-0.44	34	34

×

IL23-mediated signaling events

Figure S36. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S36. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.12	0.4	-10000	0	-1.1	45	45
IL23A	-0.15	0.42	-10000	0	-1.2	39	39
NF kappa B1 p50/RelA/I kappa B alpha	-0.2	0.34	-10000	0	-1.1	45	45
positive regulation of T cell mediated cytotoxicity	-0.15	0.44	-10000	0	-1.2	46	46
ITGA3	-0.13	0.4	-10000	0	-1.2	38	38
IL17F	-0.068	0.28	-10000	0	-0.72	34	34
IL12B	0.011	0.06	-10000	0	-0.53	5	5
STAT1 (dimer)	-0.14	0.42	-10000	0	-1.2	45	45
CD4	-0.12	0.4	-10000	0	-1.1	41	41
IL23	-0.15	0.4	-10000	0	-1.2	40	40
IL23R	0	0.083	-10000	0	-10000	0	0
IL1B	-0.16	0.46	-10000	0	-1.3	47	47
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.12	0.38	-10000	0	-1.1	37	37
TYK2	0.01	0.019	-10000	0	-10000	0	0
STAT4	0.01	0	-10000	0	-10000	0	0
STAT3	0.01	0	-10000	0	-10000	0	0
IL18RAP	-0.009	0.096	-10000	0	-0.5	18	18
IL12RB1	-0.005	0.095	-10000	0	-0.53	15	15
PIK3CA	0.01	0	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	-0.001	0.073	-10000	0	-0.39	15	15
IL23R/JAK2	0.003	0.1	-10000	0	-10000	0	0
positive regulation of chronic inflammatory response	-0.15	0.44	-10000	0	-1.2	46	46
natural killer cell activation	0.001	0.007	0.035	2	-10000	0	2
JAK2	0.015	0.042	-10000	0	-0.52	2	2
PIK3R1	0.009	0.023	-10000	0	-0.5	1	1
NFKB1	0.009	0.003	-10000	0	-10000	0	0
RELA	0.009	0.003	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.14	0.38	-10000	0	-1.1	40	40
ALOX12B	-0.14	0.4	-10000	0	-1.1	46	46
CXCL1	-0.14	0.43	-10000	0	-1.2	48	48
T cell proliferation	-0.15	0.44	-10000	0	-1.2	46	46
NFKBIA	0.009	0.003	-10000	0	-10000	0	0
IL17A	-0.047	0.23	-10000	0	-0.58	25	25
PI3K	-0.2	0.35	-10000	0	-1.1	45	45
IFNG	-0.006	0.032	-10000	0	-0.12	11	11
STAT3 (dimer)	-0.19	0.33	-10000	0	-1.1	45	45
IL18R1	-0.012	0.1	-10000	0	-0.5	21	21
IL23/IL23R/JAK2/TYK2/SOCS3	-0.058	0.25	-10000	0	-0.69	28	28
IL18/IL18R	-0.016	0.11	-10000	0	-0.35	39	39
macrophage activation	-0.013	0.016	-10000	0	-0.044	36	36
TNF	-0.15	0.44	-10000	0	-1.2	44	44
STAT3/STAT4	-0.2	0.35	-10000	0	-1.1	46	46
STAT4 (dimer)	-0.14	0.42	-10000	0	-1.2	45	45
IL18	0	0.068	-10000	0	-0.5	9	9
IL19	-0.13	0.39	-10000	0	-1.1	42	42
STAT5A (dimer)	-0.14	0.42	-10000	0	-1.2	45	45
STAT1	0.01	0	-10000	0	-10000	0	0
SOCS3	0.006	0.046	-10000	0	-0.5	4	4
CXCL9	-0.14	0.41	-10000	0	-1.1	48	48
MPO	-0.13	0.41	-10000	0	-1.1	47	47
positive regulation of humoral immune response	-0.15	0.44	-10000	0	-1.2	46	46
IL23/IL23R/JAK2/TYK2	-0.16	0.48	-10000	0	-1.3	46	46
IL6	-0.28	0.58	-10000	0	-1.2	121	121
STAT5A	0.009	0.023	-10000	0	-0.5	1	1
IL2	0.007	0.009	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0.001	0.007	0.035	2	-10000	0	2
CD3E	-0.12	0.39	-10000	0	-1.1	44	44
keratinocyte proliferation	-0.15	0.44	-10000	0	-1.2	46	46
NOS2	-0.18	0.47	-10000	0	-1.1	72	72

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.01	0.061	-10000	0	-0.54	5	5
HDAC1	0.002	0.007	-10000	0	-10000	0	0
AES	0.009	0.002	-10000	0	-10000	0	0
FBXW11	0.01	0	-10000	0	-10000	0	0
DTX1	0.007	0.041	-10000	0	-0.52	3	3
LRP6/FZD1	0	0	-10000	0	-10000	0	0
TLE1	0.009	0.002	-10000	0	-10000	0	0
AP1	-0.031	0.12	-10000	0	-0.29	79	79
NCSTN	0.01	0	-10000	0	-10000	0	0
ADAM10	0.01	0	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.01	0.057	-10000	0	-0.33	2	2
NICD/RBPSUH	-0.006	0.054	-10000	0	-0.54	5	5
WIF1	-0.34	0.23	-10000	0	-0.5	339	339
NOTCH1	-0.006	0.058	-10000	0	-0.57	5	5
PSENEN	0.009	0.024	-10000	0	-0.52	1	1
KREMEN2	-0.13	0.23	-10000	0	-0.52	126	126
DKK1	-0.13	0.23	-10000	0	-0.51	129	129
beta catenin/beta TrCP1	0.018	0.052	-10000	0	-10000	0	0
APH1B	0.008	0.032	-10000	0	-0.5	2	2
APH1A	0.01	0	-10000	0	-10000	0	0
AXIN1	-0.005	0.026	-10000	0	-0.19	3	3
CtBP/CBP/TCF1/TLE1/AES	-0.013	0.065	0.28	1	-10000	0	1
PSEN1	0.01	0	-10000	0	-10000	0	0
FOS	-0.023	0.13	-10000	0	-0.5	32	32
JUN	0.006	0.046	-10000	0	-0.5	4	4
MAP3K7	0.009	0.002	-10000	0	-10000	0	0
CTNNB1	0.013	0.055	-10000	0	-10000	0	0
MAPK3	0.01	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.14	0.19	-10000	0	-0.36	186	186
HNF1A	-0.099	0.21	-10000	0	-0.52	100	100
CTBP1	0.009	0.002	-10000	0	-10000	0	0
MYC	0.016	0.086	-10000	0	-1.3	2	2
NKD1	-0.051	0.16	-10000	0	-0.5	58	58
FZD1	0.01	0	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.007	0.057	-10000	0	-0.54	5	5
apoptosis	-0.031	0.12	-10000	0	-0.28	79	79
Delta 1/NOTCHprecursor	-0.01	0.061	-10000	0	-0.54	5	5
DLL1	0.002	0.065	-10000	0	-0.5	8	8
PPARD	0.021	0.013	-10000	0	-10000	0	0
Gamma Secretase	-0.001	0.019	-10000	0	-10000	0	0
APC	-0.005	0.026	-10000	0	-0.19	3	3
DVL1	-0.031	0.033	-10000	0	-0.43	2	2
CSNK2A1	0.01	0.001	-10000	0	-10000	0	0
MAP3K7IP1	-0.001	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.16	0.19	-10000	0	-0.35	216	216
LRP6	0.01	0	-10000	0	-10000	0	0
CSNK1A1	0.01	0.001	-10000	0	-10000	0	0
NLK	0.011	0.005	-10000	0	-10000	0	0
CCND1	0.006	0.14	-10000	0	-1.3	6	6
WNT1	-0.002	0.075	-10000	0	-0.52	10	10
Axin1/APC/beta catenin	0.012	0.041	-10000	0	-0.28	1	1
DKK2	-0.094	0.2	-10000	0	-0.5	100	100
NOTCH1 precursor/DVL1	-0.016	0.055	-10000	0	-0.49	6	6
GSK3B	0.01	0	-10000	0	-10000	0	0
FRAT1	0.009	0.001	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.007	0.057	-10000	0	-0.54	5	5
PPP2R5D	0.015	0.084	0.24	58	-10000	0	58
MAPK1	0.01	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.18	0.12	-10000	0	-0.41	11	11
RBPJ	0.01	0	-10000	0	-10000	0	0
CREBBP	0.013	0.002	-10000	0	-10000	0	0

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	-0.068	0.19	-10000	0	-0.52	74	74
NFATC2	0.004	0.17	-10000	0	-0.73	15	15
NFATC3	-0.009	0.08	-10000	0	-0.3	7	7
CD40LG	-0.071	0.36	-10000	0	-0.95	51	51
ITCH	-0.01	0.099	-10000	0	-10000	0	0
CBLB	-0.01	0.099	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.12	0.23	-10000	0	-0.94	22	22
JUNB	0.007	0.04	-10000	0	-0.5	3	3
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.051	0.1	-10000	0	-10000	0	0
T cell anergy	-0.06	0.16	-10000	0	-0.38	92	92
TLE4	0.02	0.16	-10000	0	-0.9	9	9
Jun/NFAT1-c-4/p21SNFT	-0.12	0.3	-10000	0	-0.93	48	48
AP-1/NFAT1-c-4	-0.082	0.4	-10000	0	-1.1	49	49
IKZF1	0.021	0.16	-10000	0	-0.85	10	10
T-helper 2 cell differentiation	0.007	0.19	-10000	0	-0.84	12	12
AP-1/NFAT1	-0.051	0.13	-10000	0	-0.51	23	23
CALM1	-0.011	0.066	-10000	0	-10000	0	0
EGR2	-0.047	0.39	-10000	0	-1.5	26	26
EGR3	-0.088	0.46	-10000	0	-1.4	53	53
NFAT1/FOXP3	-0.046	0.18	-10000	0	-0.53	27	27
EGR1	-0.022	0.12	-10000	0	-0.5	31	31
JUN	0.004	0.049	-10000	0	-0.5	4	4
EGR4	-0.044	0.16	-10000	0	-0.52	49	49
mol:Ca2+	-0.022	0.07	-10000	0	-10000	0	0
GBP3	0.005	0.19	-10000	0	-0.74	25	25
FOSL1	-0.015	0.11	-10000	0	-0.52	23	23
NFAT1-c-4/MAF/IRF4	-0.11	0.29	-10000	0	-0.9	46	46
DGKA	0.025	0.13	-10000	0	-0.7	8	8
CREM	0.009	0	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.14	0.32	-10000	0	-0.98	50	50
CTLA4	-0.03	0.17	-10000	0	-0.62	16	16
NFAT1-c-4 (dimer)/EGR1	-0.12	0.33	-10000	0	-0.98	52	52
NFAT1-c-4 (dimer)/EGR4	-0.13	0.31	-10000	0	-0.94	50	50
FOS	-0.026	0.13	-10000	0	-0.52	32	32
IFNG	-0.092	0.23	-10000	0	-0.91	26	26
T cell activation	0.012	0.2	-10000	0	-0.77	13	13
MAF	0.009	0.023	-10000	0	-0.5	1	1
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.028	0.28	0.92	25	-10000	0	25
TNF	-0.071	0.33	-10000	0	-0.92	51	51
FASLG	-0.11	0.48	-10000	0	-1.3	61	61
TBX21	-0.015	0.11	-10000	0	-0.5	23	23
BATF3	0.009	0.024	-10000	0	-0.52	1	1
PRKCQ	-0.065	0.18	-10000	0	-0.5	74	74
PTPN1	0.026	0.13	-10000	0	-0.74	7	7
NFAT1-c-4/ICER1	-0.11	0.3	-10000	0	-0.92	49	49
GATA3	0.008	0.04	-10000	0	-0.5	3	3
T-helper 1 cell differentiation	-0.053	0.24	-10000	0	-0.89	26	26
IL2RA	-0.12	0.22	-10000	0	-0.78	29	29
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	0.026	0.13	-10000	0	-0.74	7	7
E2F1	0.007	0.063	-10000	0	-0.51	7	7
PPARG	-0.053	0.17	-10000	0	-0.5	61	61
SLC3A2	0.026	0.13	-10000	0	-0.74	7	7
IRF4	-0.007	0.093	-10000	0	-0.51	16	16
PTGS2	-0.087	0.37	-10000	0	-0.98	54	54
CSF2	-0.08	0.36	-10000	0	-0.95	53	53
JunB/Fra1/NFAT1-c-4	-0.11	0.3	-10000	0	-0.91	47	47
IL4	0.006	0.19	-10000	0	-0.89	12	12
IL5	-0.065	0.34	-10000	0	-0.91	49	49
IL2	0.011	0.2	-10000	0	-0.78	13	13
IL3	-0.026	0.046	-10000	0	-10000	0	0
RNF128	-0.08	0.24	-10000	0	-0.57	93	93
NFATC1	-0.029	0.28	-10000	0	-0.93	25	25
CDK4	0.007	0.17	0.57	18	-10000	0	18
PTPRK	0.026	0.13	-10000	0	-0.74	7	7
IL8	-0.071	0.35	-10000	0	-0.91	50	50
POU2F1	0.01	0.001	-10000	0	-10000	0	0

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.14	0.22	-10000	0	-0.64	19	19
CRP	-0.15	0.23	-10000	0	-0.68	16	16
cell cycle arrest	-0.17	0.25	-10000	0	-0.57	83	83
TIMP1	-0.11	0.19	-10000	0	-0.66	9	9
IL6ST	-0.011	0.093	-10000	0	-0.5	17	17
Rac1/GDP	-0.067	0.14	-10000	0	-0.42	24	24
AP1	0.001	0.09	-10000	0	-0.59	3	3
GAB2	0.008	0.046	-10000	0	-0.5	4	4
TNFSF11	-0.19	0.25	-10000	0	-0.64	45	45
HSP90B1	-0.004	0.044	-10000	0	-10000	0	0
GAB1	0.008	0.04	-10000	0	-0.5	3	3
MAPK14	-0.045	0.14	-10000	0	-0.52	17	17
AKT1	0.036	0.033	-10000	0	-10000	0	0
FOXO1	0.041	0.031	-10000	0	-10000	0	0
MAP2K6	-0.063	0.14	-10000	0	-0.47	20	20
mol:GTP	-0.002	0.002	-10000	0	-10000	0	0
MAP2K4	-0.08	0.16	-10000	0	-0.48	19	19
MITF	-0.069	0.14	-10000	0	-0.35	55	55
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.01	0	-10000	0	-10000	0	0
A2M	-0.081	0.34	-10000	0	-1.3	37	37
CEBPB	0.015	0.003	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	-0.009	0.082	0.22	1	-0.5	4	5
STAT3	-0.17	0.26	-10000	0	-0.59	83	83
STAT1	-0.002	0.012	-10000	0	-10000	0	0
CEBPD	-0.14	0.23	-10000	0	-0.69	19	19
PIK3CA	0.011	0	-10000	0	-10000	0	0
PI3K	0.015	0.017	-10000	0	-0.35	1	1
JUN	0.006	0.046	-10000	0	-0.5	4	4
PIAS3/MITF	-0.059	0.14	-10000	0	-0.42	23	23
MAPK11	-0.047	0.14	-10000	0	-0.52	18	18
STAT3 (dimer)/FOXO1	-0.12	0.23	-10000	0	-0.65	29	29
GRB2/SOS1/GAB family	-0.058	0.12	-10000	0	-0.44	20	20
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.064	0.15	-10000	0	-0.34	75	75
GRB2	0.011	0.004	-10000	0	-10000	0	0
JAK2	0.008	0.032	-10000	0	-0.5	2	2
LBP	-0.13	0.2	-10000	0	-0.6	14	14
PIK3R1	0.01	0.023	-10000	0	-0.5	1	1
JAK1	0.009	0.005	-10000	0	-10000	0	0
MYC	-0.14	0.23	-10000	0	-0.65	21	21
FGG	-0.33	0.46	-10000	0	-0.99	148	148
macrophage differentiation	-0.17	0.25	-10000	0	-0.57	83	83
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.071	0.12	-10000	0	-0.43	15	15
JUNB	-0.14	0.22	-10000	0	-0.73	14	14
FOS	-0.023	0.13	-10000	0	-0.5	32	32
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.076	0.14	-10000	0	-0.35	68	68
STAT1/PIAS1	-0.079	0.14	-10000	0	-0.34	61	61
GRB2/SOS1/GAB family/SHP2/PI3K	0.018	0.038	-10000	0	-0.26	2	2
STAT3 (dimer)	-0.17	0.26	-10000	0	-0.59	83	83
PRKCD	-0.095	0.18	-10000	0	-0.55	16	16
IL6R	-0.002	0.076	-10000	0	-0.5	11	11
SOCS3	-0.035	0.16	-10000	0	-0.73	11	11
gp130 (dimer)/JAK1/JAK1/LMO4	0.001	0.061	-10000	0	-0.29	18	18
Rac1/GTP	-0.078	0.15	-10000	0	-0.39	40	40
HCK	-0.012	0.1	-10000	0	-0.5	21	21
MAPKKK cascade	0.009	0.08	-10000	0	-0.59	4	4
bone resorption	-0.18	0.24	-10000	0	-0.61	45	45
IRF1	-0.14	0.22	-10000	0	-0.67	15	15
mol:GDP	-0.07	0.14	-10000	0	-0.38	40	40
SOS1	0.012	0.006	-10000	0	-10000	0	0
VAV1	-0.071	0.15	-10000	0	-0.39	40	40
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.04	0.14	-10000	0	-0.5	20	20
PTPN11	-0.001	0.01	-10000	0	-10000	0	0
IL6/IL6RA	-0.082	0.16	-10000	0	-0.36	120	120
gp130 (dimer)/TYK2/TYK2/LMO4	-0.001	0.059	-10000	0	-0.29	18	18
gp130 (dimer)/JAK2/JAK2/LMO4	-0.002	0.062	-10000	0	-0.29	20	20
IL6	-0.11	0.21	-10000	0	-0.5	111	111
PIAS3	0.01	0	-10000	0	-10000	0	0
PTPRE	0.012	0.034	-10000	0	-0.49	2	2
PIAS1	0.01	0	-10000	0	-10000	0	0
RAC1	0.009	0.001	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.066	0.13	-10000	0	-0.3	89	89
LMO4	0.006	0.024	-10000	0	-0.5	1	1
STAT3 (dimer)/PIAS3	-0.19	0.21	-10000	0	-0.58	64	64
MCL1	0.042	0.03	-10000	0	-10000	0	0

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	-0.011	0.069	-9999	-0.3	2	2
BIRC5	-0.29	0.26	-9999	-0.52	281	281
NFKBIA	-0.009	0.067	-9999	-10000	0	0
CPEB1	-0.064	0.18	-9999	-0.5	70	70
AKT1	-0.009	0.067	-9999	-10000	0	0
NDEL1	0.01	0	-9999	-10000	0	0
Aurora A/BRCA1	-0.017	0.063	-9999	-0.36	3	3
NDEL1/TACC3	-0.012	0.058	-9999	-0.38	2	2
GADD45A	0.008	0.033	-9999	-0.51	2	2
GSK3B	0.012	0.003	-9999	-10000	0	0
PAK1/Aurora A	-0.01	0.067	-9999	-10000	0	0
MDM2	0.008	0.034	-9999	-0.52	2	2
JUB	0.008	0.032	-9999	-0.5	2	2
TPX2	-0.19	0.19	-9999	-0.37	268	268
TP53	0.002	0.045	-9999	-10000	0	0
DLG7	-0.017	0.067	-9999	-10000	0	0
AURKAIP1	0.009	0.023	-9999	-0.5	1	1
ARHGEF7	0.01	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	-0.013	0.061	-9999	-0.41	2	2
G2/M transition of mitotic cell cycle	-0.017	0.063	-9999	-0.36	3	3
AURKA	-0.019	0.083	-9999	-10000	0	0
AURKB	-0.058	0.055	-9999	-10000	0	0
CDC25B	-0.012	0.054	-9999	-0.22	1	1
G2/M transition checkpoint	-0.017	0.06	-9999	-0.33	2	2
mRNA polyadenylation	-0.056	0.12	-9999	-0.3	70	70
Aurora A/CPEB	-0.056	0.12	-9999	-0.3	70	70
Aurora A/TACC1/TRAP/chTOG	-0.017	0.075	-9999	-0.37	6	6
BRCA1	0.007	0.041	-9999	-0.52	3	3
centrosome duplication	-0.01	0.067	-9999	-10000	0	0
regulation of centrosome cycle	-0.013	0.057	-9999	-0.38	2	2
spindle assembly	-0.018	0.073	-9999	-0.36	6	6
TDRD7	0.01	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.16	0.15	-9999	-0.37	91	91
CENPA	-0.054	0.054	-9999	-10000	0	0
Aurora A/PP2A	-0.01	0.067	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.004	0.051	-9999	-10000	0	0
negative regulation of DNA binding	0.002	0.045	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0	0	-9999	-10000	0	0
RASA1	0.01	0	-9999	-10000	0	0
Ajuba/Aurora A	-0.017	0.06	-9999	-0.33	2	2
mitotic prometaphase	0.015	0.015	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.018	0.083	-9999	-10000	0	0
TACC1	-0.011	0.1	-9999	-0.5	20	20
TACC3	0.008	0.034	-9999	-0.52	2	2
Aurora A/Antizyme1	-0.012	0.058	-9999	-0.26	1	1
Aurora A/RasGAP	-0.01	0.067	-9999	-10000	0	0
OAZ1	0.01	0	-9999	-10000	0	0
RAN	0.009	0.024	-9999	-0.52	1	1
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.012	0.003	-9999	-10000	0	0
GIT1	0.01	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0	0	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.19	0.19	-9999	-0.37	268	268
PPP2R5D	0.01	0	-9999	-10000	0	0
Aurora A/TPX2	-0.16	0.18	-9999	-0.32	268	268
PAK1	0.01	0	-9999	-10000	0	0
CKAP5	0.01	0	-9999	-10000	0	0

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	-0.13	0.23	-9999	-0.5	132	132
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.01	0	-9999	-10000	0	0
TCEB1	0.008	0.034	-9999	-0.52	2	2
HIF1A/p53	0.005	0.035	-9999	-10000	0	0
HIF1A	-0.001	0.037	-9999	-10000	0	0
COPS5	0.01	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	-0.001	0.016	-9999	-10000	0	0
FIH (dimer)	0.01	0	-9999	-10000	0	0
CDKN2A	-0.15	0.24	-9999	-0.52	145	145
ARNT/IPAS	-0.095	0.16	-9999	-0.35	132	132
HIF1AN	0.01	0	-9999	-10000	0	0
GNB2L1	0.01	0	-9999	-10000	0	0
HIF1A/ARNT	0.005	0.035	-9999	-10000	0	0
CUL2	0.01	0	-9999	-10000	0	0
OS9	0.01	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	-0.001	0.019	-9999	-0.3	2	2
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.005	0.035	-9999	-10000	0	0
PHD1-3/OS9	-0.069	0.12	-9999	-0.27	124	124
HIF1A/RACK1/Elongin B/Elongin C	-0.011	0.023	-9999	-0.28	1	1
VHL	0.01	0	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
HIF1A/JAB1	0.005	0.035	-9999	-10000	0	0
EGLN3	-0.12	0.23	-9999	-0.52	125	125
EGLN2	0.01	0	-9999	-10000	0	0
EGLN1	0.01	0	-9999	-10000	0	0
TP53	0.01	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.025	0.01	-9999	-10000	0	0
ARNT	0.01	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.01	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.071	0.13	-9999	-0.26	145	145

×

PDGFR-alpha 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
PDGFRA	0.005	0.047	-9999	-0.5	4	4
PDGF/PDGFRA/CRKL	-0.003	0.031	-9999	-0.34	4	4
positive regulation of JUN kinase activity	-0.003	0.025	-9999	-0.27	1	1
CRKL	0.01	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.084	0.15	-9999	-0.36	113	113
AP1	-0.06	0.22	-9999	-0.87	32	32
mol:IP3	0.014	0.037	-9999	-0.35	4	4
PLCG1	0.014	0.037	-9999	-0.35	4	4
PDGF/PDGFRA/alphaV Integrin	-0.003	0.031	-9999	-0.34	4	4
RAPGEF1	0.01	0	-9999	-10000	0	0
CRK	0.01	0	-9999	-10000	0	0
mol:Ca2+	0.014	0.037	-9999	-0.35	4	4
CAV3	-0.11	0.21	-9999	-0.5	109	109
CAV1	-0.32	0.24	-9999	-0.5	313	313
SHC/Grb2/SOS1	-0.003	0.025	-9999	-0.27	1	1
PDGF/PDGFRA/Shf	-0.005	0.039	-9999	-0.35	6	6
FOS	-0.025	0.22	-9999	-0.86	32	32
JUN	-0.007	0.035	-9999	-0.36	4	4
oligodendrocyte development	-0.003	0.031	-9999	-0.34	4	4
GRB2	0.01	0	-9999	-10000	0	0
PIK3R1	0.009	0.023	-9999	-0.5	1	1
mol:DAG	0.014	0.037	-9999	-0.35	4	4
PDGF/PDGFRA	0.005	0.047	-9999	-0.5	4	4
actin cytoskeleton reorganization	-0.004	0.035	-9999	-0.35	5	5
SRF	0.018	0.006	-9999	-10000	0	0
SHC1	0.009	0.024	-9999	-0.52	1	1
PI3K	-0.003	0.028	-9999	-0.28	5	5
PDGF/PDGFRA/Crk/C3G	-0.002	0.025	-9999	-0.28	4	4
JAK1	0.015	0.033	-9999	-0.34	4	4
ELK1/SRF	0.027	0.028	-9999	-10000	0	0
SHB	0.009	0.023	-9999	-0.5	1	1
SHF	0.008	0.034	-9999	-0.52	2	2
CSNK2A1	0.004	0.014	-9999	-10000	0	0
GO:0007205	0.014	0.039	-9999	-0.37	4	4
SOS1	0.01	0	-9999	-10000	0	0
Ras protein signal transduction	-0.003	0.025	-9999	-0.27	1	1
PDGF/PDGFRA/SHB	-0.004	0.035	-9999	-0.35	5	5
PDGF/PDGFRA/Caveolin-1	-0.23	0.18	-9999	-0.36	314	314
ITGAV	0.01	0	-9999	-10000	0	0
ELK1	0.018	0.04	-9999	-0.31	4	4
PIK3CA	0.01	0	-9999	-10000	0	0
PDGF/PDGFRA/Crk	-0.003	0.031	-9999	-0.34	4	4
JAK-STAT cascade	0.015	0.033	-9999	-0.34	4	4
cell proliferation	-0.005	0.039	-9999	-0.35	6	6

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.027	0.024	-9999	-10000	0	0
VDR	0.008	0.033	-9999	-0.51	2	2
FAM120B	0.01	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.094	0.14	-9999	-0.46	11	11
RXRs/LXRs/DNA/Oxysterols	-0.075	0.14	-9999	-0.48	20	20
MED1	0.01	0	-9999	-10000	0	0
mol:9cRA	0.003	0.009	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	0.003	0.078	-9999	-0.46	1	1
RXRs/NUR77	-0.17	0.18	-9999	-0.48	63	63
RXRs/PPAR	-0.13	0.16	-9999	-0.43	50	50
NCOR2	0.01	0	-9999	-10000	0	0
VDR/VDR/Vit D3	-0.002	0.023	-9999	-0.37	2	2
RARs/VDR/DNA/Vit D3	-0.002	0.022	-9999	-0.24	4	4
RARA	0.01	0	-9999	-10000	0	0
NCOA1	0.01	0	-9999	-10000	0	0
VDR/VDR/DNA	0.008	0.033	-9999	-0.51	2	2
RARs/RARs/DNA/9cRA	-0.001	0.016	-9999	-0.25	2	2
RARG	0.01	0	-9999	-10000	0	0
RPS6KB1	0.044	0.04	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	0.003	0.078	-9999	-0.46	1	1
THRA	0.01	0	-9999	-10000	0	0
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	-0.002	0.023	-9999	-0.37	2	2
RXRs/PPAR/9cRA/PGJ2/DNA	-0.12	0.14	-9999	-0.37	11	11
NR1H4	-0.032	0.14	-9999	-0.52	35	35
RXRs/LXRs/DNA	-0.097	0.14	-9999	-0.39	11	11
NR1H2	0.014	0.007	-9999	-10000	0	0
NR1H3	0.013	0.008	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.11	0.14	-9999	-0.32	13	13
NR4A1	-0.091	0.2	-9999	-0.5	97	97
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.1	0.12	-9999	-0.31	31	31
RXRG	-0.26	0.25	-9999	-0.5	259	259
RXR alpha/CCPG	0.018	0.004	-9999	-10000	0	0
RXRA	0.013	0.007	-9999	-10000	0	0
RXRB	0.013	0.008	-9999	-10000	0	0
THRB	-0.041	0.15	-9999	-0.5	49	49
PPARG	-0.054	0.17	-9999	-0.5	61	61
PPARD	0.01	0	-9999	-10000	0	0
TNF	-0.086	0.22	-9999	-1	19	19
mol:Oxysterols	0.003	0.009	-9999	-10000	0	0
cholesterol transport	-0.075	0.14	-9999	-0.48	20	20
PPARA	0.01	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	0.008	0.032	-9999	-0.5	2	2
RXRs/NUR77/BCL2	-0.16	0.16	-9999	-0.26	306	306
SREBF1	-0.062	0.13	-9999	-0.53	11	11
RXRs/RXRs/DNA/9cRA	-0.12	0.14	-9999	-0.37	11	11
ABCA1	-0.065	0.14	-9999	-0.61	12	12
RARs/THRs	-0.025	0.074	-9999	-0.49	1	1
RXRs/FXR	-0.14	0.16	-9999	-0.46	31	31
BCL2	0.007	0.041	-9999	-0.51	3	3

×

Nongenotropic Androgen signaling

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
PTK2	0.009	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.035	0.092	-10000	0	-0.27	65	65
regulation of S phase of mitotic cell cycle	-0.009	0.085	-10000	0	-0.23	62	62
GNAO1	0.004	0.057	-10000	0	-0.51	6	6
HRAS	0.01	0.001	-10000	0	-10000	0	0
SHBG/T-DHT	-0.001	0.02	-10000	0	-0.32	2	2
PELP1	0.01	0.001	-10000	0	-10000	0	0
AKT1	0.009	0	-10000	0	-10000	0	0
MAP2K1	0.001	0.09	-10000	0	-0.31	12	12
T-DHT/AR	-0.047	0.12	-10000	0	-0.36	64	64
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.002	-10000	0	-0.006	32	32
GNAI2	0.01	0	-10000	0	-10000	0	0
GNAI3	0.01	0	-10000	0	-10000	0	0
GNAI1	0.008	0.032	-10000	0	-0.5	2	2
mol:GDP	-0.051	0.13	-10000	0	-0.4	62	62
cell proliferation	0	0.14	-10000	0	-0.42	32	32
PIK3CA	0.01	0	-10000	0	-10000	0	0
FOS	-0.02	0.21	-10000	0	-0.79	32	32
mol:Ca2+	-0.01	0.022	-10000	0	-0.064	49	49
MAPK3	0.001	0.11	-10000	0	-0.45	12	12
MAPK1	0.005	0.067	-10000	0	-0.26	12	12
PIK3R1	0.009	0.023	-10000	0	-0.5	1	1
mol:IP3	0	0.001	-10000	0	-0.004	32	32
cAMP biosynthetic process	0.008	0.028	-10000	0	-0.31	2	2
GNG2	0.008	0.032	-10000	0	-0.5	2	2
potassium channel inhibitor activity	0	0.001	-10000	0	-0.004	32	32
HRAS/GTP	-0.033	0.081	-10000	0	-0.28	13	13
actin cytoskeleton reorganization	0	0.01	-10000	0	-10000	0	0
SRC	0.01	0.001	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.004	32	32
PI3K	-0.001	0.013	-10000	0	-0.3	1	1
apoptosis	0.001	0.12	0.43	32	-10000	0	32
T-DHT/AR/PELP1	-0.039	0.1	-10000	0	-0.3	64	64
HRAS/GDP	-0.048	0.12	-10000	0	-0.37	62	62
CREB1	-0.003	0.13	-10000	0	-0.46	32	32
RAC1-CDC42/GTP	0	0.01	-10000	0	-10000	0	0
AR	-0.057	0.17	-10000	0	-0.5	64	64
GNB1	0.01	0	-10000	0	-10000	0	0
RAF1	-0.004	0.089	-10000	0	-0.3	12	12
RAC1-CDC42/GDP	-0.045	0.12	-10000	0	-0.35	62	62
T-DHT/AR/PELP1/Src	-0.035	0.09	-10000	0	-0.27	64	64
MAP2K2	0.001	0.09	-10000	0	-0.31	12	12
T-DHT/AR/PELP1/Src/PI3K	-0.009	0.086	-10000	0	-0.23	62	62
GNAZ	-0.033	0.14	-10000	0	-0.5	41	41
SHBG	0.007	0.034	-10000	0	-0.52	2	2
Gi family/GNB1/GNG2/GDP	0.005	0.079	-10000	0	-0.39	4	4
mol:T-DHT	0	0.001	0.001	1	-0.003	20	21
RAC1	0.01	0	-10000	0	-10000	0	0
GNRH1	0.006	0.033	-10000	0	-0.36	4	4
Gi family/GTP	-0.035	0.082	-10000	0	-0.25	44	44
CDC42	0.01	0	-10000	0	-10000	0	0

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.031	0.12	-9999	-0.47	16	16
FZD6	0.009	0.023	-9999	-0.5	1	1
WNT6	-0.021	0.12	-9999	-0.52	28	28
WNT4	-0.022	0.12	-9999	-0.5	30	30
FZD3	0.009	0.024	-9999	-0.52	1	1
WNT5A	0.005	0.051	-9999	-0.5	5	5
WNT11	-0.059	0.17	-9999	-0.5	66	66

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	0.012	0.1	0.5	21	-10000	0	21
PI3K Class IB/PDE3B	-0.012	0.1	-10000	0	-0.5	21	21
PDE3B	-0.012	0.1	-10000	0	-0.5	21	21

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	-0.009	0.037	-10000	0	-10000	0	0
oxygen homeostasis	0	0.014	-10000	0	-10000	0	0
TCEB2	0.01	0	-10000	0	-10000	0	0
TCEB1	0.008	0.034	-10000	0	-0.52	2	2
VHL/Elongin B/Elongin C/HIF2A	-0.069	0.12	-10000	0	-0.38	39	39
EPO	-0.032	0.23	-10000	0	-0.66	15	15
FIH (dimer)	0.01	0.012	-10000	0	-10000	0	0
APEX1	0.012	0.012	-10000	0	-10000	0	0
SERPINE1	-0.054	0.26	-10000	0	-0.7	27	27
FLT1	-0.009	0.053	-10000	0	-0.89	1	1
ADORA2A	-0.049	0.25	-10000	0	-0.65	26	26
germ cell development	-0.066	0.26	-10000	0	-0.65	32	32
SLC11A2	-0.052	0.26	-10000	0	-0.67	26	26
BHLHE40	-0.052	0.26	-10000	0	-0.67	26	26
HIF1AN	0.01	0.012	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.091	0.15	-10000	0	-0.44	45	45
ETS1	0.021	0.025	-10000	0	-0.52	1	1
CITED2	-0.009	0.048	-10000	0	-0.96	1	1
KDR	-0.033	0.18	-10000	0	-1.2	12	12
PGK1	-0.052	0.26	-10000	0	-0.66	27	27
SIRT1	0.01	0	-10000	0	-10000	0	0
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	-0.066	0.29	-10000	0	-0.77	30	30
EPAS1	-0.047	0.17	-10000	0	-0.39	57	57
SP1	0.016	0.001	-10000	0	-10000	0	0
ABCG2	-0.078	0.3	-10000	0	-0.76	44	44
EFNA1	-0.052	0.26	-10000	0	-0.67	27	27
FXN	-0.049	0.25	-10000	0	-0.65	26	26
POU5F1	-0.07	0.27	-10000	0	-0.68	32	32
neuron apoptosis	0.064	0.28	0.74	30	-10000	0	30
EP300	0.01	0	-10000	0	-10000	0	0
EGLN3	-0.13	0.24	-10000	0	-0.53	125	125
EGLN2	0.01	0.012	-10000	0	-10000	0	0
EGLN1	0.01	0.012	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	-0.001	0.019	-10000	0	-0.3	2	2
VHL	0.01	0	-10000	0	-10000	0	0
ARNT	0.012	0.012	-10000	0	-10000	0	0
SLC2A1	-0.13	0.32	-10000	0	-0.65	84	84
TWIST1	-0.09	0.3	-10000	0	-0.67	59	59
ELK1	0.016	0.004	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.089	0.14	-10000	0	-0.44	43	43
VEGFA	-0.052	0.26	-10000	0	-0.66	27	27
CREBBP	0.01	0	-10000	0	-10000	0	0

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	-0.011	0.063	-9999	-0.37	15	15
VLDLR	-0.002	0.075	-9999	-0.5	11	11
CRKL	0.01	0	-9999	-10000	0	0
LRPAP1	0.01	0	-9999	-10000	0	0
FYN	0.009	0.023	-9999	-0.5	1	1
ITGA3	0.006	0.046	-9999	-0.5	4	4
RELN/VLDLR/Fyn	-0.052	0.12	-9999	-0.31	81	81
MAPK8IP1/MKK7/MAP3K11/JNK1	0	0.011	-9999	-10000	0	0
AKT1	-0.015	0.097	-9999	-0.39	8	8
MAP2K7	0.01	0	-9999	-10000	0	0
RAPGEF1	0.01	0	-9999	-10000	0	0
DAB1	-0.003	0.067	-9999	-0.52	8	8
RELN/LRP8/DAB1	-0.052	0.11	-9999	-0.28	90	90
LRPAP1/LRP8	-0.008	0.054	-9999	-0.37	11	11
RELN/LRP8/DAB1/Fyn	-0.048	0.1	-9999	-0.3	25	25
DAB1/alpha3/beta1 Integrin	-0.048	0.1	-9999	-0.45	10	10
long-term memory	-0.095	0.14	-9999	-0.51	25	25
DAB1/LIS1	-0.048	0.1	-9999	-0.47	9	9
DAB1/CRLK/C3G	-0.046	0.098	-9999	-0.45	9	9
PIK3CA	0.01	0	-9999	-10000	0	0
DAB1/NCK2	-0.049	0.1	-9999	-0.47	9	9
ARHGEF2	0.01	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.089	0.2	-9999	-0.51	93	93
CDK5R1	-0.006	0.091	-9999	-0.52	15	15
RELN	-0.069	0.18	-9999	-0.5	75	75
PIK3R1	0.009	0.023	-9999	-0.5	1	1
RELN/LRP8/Fyn	-0.052	0.11	-9999	-0.3	86	86
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.094	0.14	-9999	-0.52	21	21
MAPK8	0.01	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.052	0.12	-9999	-0.29	86	86
ITGB1	0.01	0	-9999	-10000	0	0
MAP1B	-0.033	0.12	-9999	-0.48	12	12
RELN/LRP8	-0.052	0.11	-9999	-0.29	86	86
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.053	0.11	-9999	-0.51	10	10
PI3K	-0.001	0.016	-9999	-0.35	1	1
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.003	0.032	-9999	-0.35	4	4
RAP1A	-0.008	0.11	-9999	-0.42	9	9
PAFAH1B1	0.01	0	-9999	-10000	0	0
MAPK8IP1	0.01	0	-9999	-10000	0	0
CRLK/C3G	0	0	-9999	-10000	0	0
GRIN2B	-0.009	0.074	-9999	-0.52	10	10
NCK2	0.01	0	-9999	-10000	0	0
neuron differentiation	0.001	0.072	-9999	-0.31	3	3
neuron adhesion	0.002	0.11	-9999	-0.4	10	10
LRP8	-0.002	0.078	-9999	-0.52	11	11
GSK3B	-0.008	0.093	-9999	-0.38	7	7
RELN/VLDLR/DAB1/Fyn	-0.048	0.11	-9999	-0.27	86	86
MAP3K11	0.009	0.023	-9999	-0.5	1	1
RELN/VLDLR/DAB1/P13K	-0.023	0.1	-9999	-0.25	76	76
CDK5	0.01	0	-9999	-10000	0	0
MAPT	-0.018	0.11	-9999	-0.46	27	27
neuron migration	-0.01	0.13	-9999	-0.43	10	10
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	0.001	0.073	-9999	-0.31	3	3
RELN/VLDLR	-0.052	0.11	-9999	-0.32	23	23

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.018	0.001	-9999	-10000	0	0
SMARCC1	0.003	0.006	-9999	-10000	0	0
REL	0.01	0.001	-9999	-10000	0	0
HDAC7	0.023	0.091	-9999	-0.41	5	5
JUN	0.006	0.046	-9999	-0.5	4	4
EP300	0.01	0	-9999	-10000	0	0
KAT2B	0.01	0	-9999	-10000	0	0
KAT5	0.01	0	-9999	-10000	0	0
MAPK14	0.004	0.075	-9999	-0.37	19	19
FOXO1	0.01	0	-9999	-10000	0	0
T-DHT/AR	0.02	0.096	-9999	-0.42	6	6
MAP2K6	-0.01	0.1	-9999	-0.52	19	19
BRM/BAF57	-0.003	0.032	-9999	-0.35	4	4
MAP2K4	0.01	0.004	-9999	-10000	0	0
SMARCA2	0.006	0.046	-9999	-0.5	4	4
PDE9A	-0.045	0.17	-9999	-1.2	8	8
NCOA2	0.006	0.046	-9999	-0.5	4	4
CEBPA	-0.016	0.11	-9999	-0.5	25	25
EHMT2	0.01	0.001	-9999	-10000	0	0
cell proliferation	0.019	0.13	-9999	-0.45	19	19
NR0B1	-0.1	0.21	-9999	-0.52	97	97
EGR1	-0.022	0.12	-9999	-0.5	31	31
RXRs/9cRA	-0.14	0.13	-9999	-0.26	259	259
AR/RACK1/Src	-0.002	0.067	-9999	-0.36	3	3
AR/GR	-0.006	0.096	-9999	-0.3	24	24
GNB2L1	0.01	0.001	-9999	-10000	0	0
PKN1	0.01	0	-9999	-10000	0	0
RCHY1	0.01	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0.002	-9999	-10000	0	0
MAPK8	0.019	0.009	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.003	0.07	-9999	-0.38	3	3
SRC	0.022	0.059	-9999	-0.29	5	5
NR3C1	0.01	0	-9999	-10000	0	0
KLK3	-0.066	0.1	-9999	-0.52	2	2
APPBP2	0.01	0.004	-9999	-10000	0	0
TRIM24	0.01	0.001	-9999	-10000	0	0
T-DHT/AR/TIP60	0.013	0.072	-9999	-0.4	3	3
TMPRSS2	-0.1	0.3	-9999	-1.1	40	40
RXRG	-0.26	0.25	-9999	-0.5	259	259
mol:9cRA	0	0	-9999	-10000	0	0
RXRA	0.01	0	-9999	-10000	0	0
RXRB	0.01	0	-9999	-10000	0	0
CARM1	0.01	0.002	-9999	-10000	0	0
NR2C2	0.01	0	-9999	-10000	0	0
KLK2	0.013	0.098	-9999	-0.4	8	8
AR	-0.011	0.11	-9999	-0.33	27	27
SENP1	0.01	0	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
MDM2	0.008	0.034	-9999	-0.52	2	2
SRY	0.001	0.004	-9999	-10000	0	0
GATA2	-0.033	0.14	-9999	-0.5	41	41
MYST2	0.01	0	-9999	-10000	0	0
HOXB13	-0.19	0.25	-9999	-0.52	179	179
T-DHT/AR/RACK1/Src	0.018	0.071	-9999	-0.38	3	3
positive regulation of transcription	-0.033	0.14	-9999	-0.5	41	41
DNAJA1	0.01	0.004	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.023	0.009	-9999	-10000	0	0
NCOA1	0.013	0.003	-9999	-10000	0	0
SPDEF	-0.17	0.25	-9999	-0.52	167	167
T-DHT/AR/TIF2	0.027	0.052	-9999	-10000	0	0
T-DHT/AR/Hsp90	0.013	0.072	-9999	-0.37	4	4
GSK3B	0.01	0.003	-9999	-10000	0	0
NR2C1	0.01	0	-9999	-10000	0	0
mol:T-DHT	0.017	0.063	-9999	-0.29	9	9
SIRT1	0.01	0	-9999	-10000	0	0
ZMIZ2	0.01	0.002	-9999	-10000	0	0
POU2F1	0.016	0.023	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.06	0.13	-9999	-0.38	33	33
CREBBP	0.01	0	-9999	-10000	0	0
SMARCE1	0.01	0.001	-9999	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.009	0.023	-9999	-0.5	1	1
PLK4	-0.018	0.12	-9999	-0.52	26	26
regulation of centriole replication	-0.003	0.088	-9999	-0.37	27	27

×

Syndecan-4-mediated signaling events

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
PTK2	0.01	0.048	-9999	-0.48	4	4
Syndecan-4/Syndesmos	-0.024	0.087	-9999	-0.53	2	2
positive regulation of JNK cascade	-0.054	0.085	-9999	-0.35	15	15
Syndecan-4/ADAM12	-0.11	0.16	-9999	-0.38	88	88
CCL5	0.005	0.051	-9999	-0.5	5	5
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0.01	0	-9999	-10000	0	0
ITGA5	0.008	0.033	-9999	-0.51	2	2
SDCBP	0.01	0	-9999	-10000	0	0
PLG	-0.006	0.072	-9999	-0.52	9	9
ADAM12	-0.17	0.25	-9999	-0.52	166	166
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.01	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.036	0.05	-9999	-0.16	1	1
Syndecan-4/Laminin alpha1	-0.037	0.11	-9999	-0.41	14	14
Syndecan-4/CXCL12/CXCR4	-0.033	0.1	-9999	-0.37	14	14
Syndecan-4/Laminin alpha3	-0.073	0.13	-9999	-0.37	37	37
MDK	-0.15	0.24	-9999	-0.52	151	151
Syndecan-4/FZD7	-0.024	0.089	-9999	-0.47	3	3
Syndecan-4/Midkine	-0.1	0.15	-9999	-0.38	57	57
FZD7	0.009	0.023	-9999	-0.5	1	1
Syndecan-4/FGFR1/FGF	-0.07	0.11	-9999	-0.48	10	10
THBS1	0.007	0.04	-9999	-0.5	3	3
integrin-mediated signaling pathway	-0.04	0.11	-9999	-0.41	11	11
positive regulation of MAPKKK cascade	-0.054	0.085	-9999	-0.35	15	15
Syndecan-4/TACI	-0.044	0.12	-9999	-0.39	23	23
CXCR4	0.01	0	-9999	-10000	0	0
cell adhesion	0.007	0.039	-9999	-0.33	4	4
Syndecan-4/Dynamin	-0.024	0.087	-9999	-0.53	2	2
Syndecan-4/TSP1	-0.025	0.092	-9999	-0.63	2	2
Syndecan-4/GIPC	-0.024	0.087	-9999	-0.53	2	2
Syndecan-4/RANTES	-0.026	0.089	-9999	-0.53	2	2
ITGB1	0.01	0	-9999	-10000	0	0
LAMA1	-0.018	0.12	-9999	-0.51	26	26
LAMA3	-0.093	0.2	-9999	-0.5	99	99
RAC1	0.01	0	-9999	-10000	0	0
PRKCA	0.016	0.04	-9999	-0.46	2	2
Syndecan-4/alpha-Actinin	-0.024	0.087	-9999	-0.53	2	2
TFPI	-0.012	0.1	-9999	-0.5	21	21
F2	-0.073	0.18	-9999	-0.52	71	71
alpha5/beta1 Integrin	-0.001	0.023	-9999	-0.36	2	2
positive regulation of cell adhesion	-0.078	0.14	-9999	-0.39	32	32
ACTN1	0.01	0	-9999	-10000	0	0
TNC	-0.028	0.14	-9999	-0.51	35	35
Syndecan-4/CXCL12	-0.039	0.11	-9999	-0.39	15	15
FGF6	0	0.001	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
CXCL12	-0.022	0.12	-9999	-0.5	31	31
TNFRSF13B	-0.033	0.14	-9999	-0.51	40	40
FGF2	-0.059	0.17	-9999	-0.5	66	66
FGFR1	0.007	0.04	-9999	-0.5	3	3
Syndecan-4/PI-4-5-P2	-0.03	0.087	-9999	-0.53	2	2
mol:GDP	0	0	-9999	-10000	0	0
FN1	0.007	0.051	-9999	-0.49	5	5
cell migration	-0.015	0.021	-9999	-10000	0	0
PRKCD	0.012	0.006	-9999	-10000	0	0
vasculogenesis	-0.024	0.089	-9999	-0.6	2	2
SDC4	-0.031	0.091	-9999	-0.56	2	2
Syndecan-4/Tenascin C	-0.042	0.11	-9999	-0.42	11	11
Syndecan-4/PI-4-5-P2/PKC alpha	-0.028	0.04	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.024	0.087	-9999	-0.53	2	2
MMP9	-0.098	0.21	-9999	-0.52	99	99
Rac1/GTP	0.005	0.039	-9999	-0.34	4	4
cytoskeleton organization	-0.023	0.085	-9999	-0.51	2	2
GIPC1	0.01	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.034	0.1	-9999	-0.43	7	7

×

Coregulation of Androgen receptor activity

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
NRIP1	0.01	0.001	-9999	-10000	0	0
SVIL	0.01	0.001	-9999	-10000	0	0
ZNF318	0.009	0.007	-9999	-10000	0	0
JMJD2C	-0.001	0.018	-9999	-0.079	24	24
T-DHT/AR/Ubc9	-0.036	0.12	-9999	-0.33	64	64
CARM1	0.01	0	-9999	-10000	0	0
PRDX1	0.009	0.024	-9999	-0.52	1	1
PELP1	0.01	0.001	-9999	-10000	0	0
CTNNB1	0.01	0.001	-9999	-10000	0	0
AKT1	0.01	0.002	-9999	-10000	0	0
PTK2B	0.008	0.033	-9999	-0.5	2	2
MED1	0.01	0.002	-9999	-10000	0	0
MAK	-0.007	0.088	-9999	-0.5	15	15
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	0.005	0.051	-9999	-0.5	5	5
GSN	0.01	0.001	-9999	-10000	0	0
NCOA2	0.006	0.046	-9999	-0.5	4	4
NCOA6	0.01	0.001	-9999	-10000	0	0
DNA-PK	0.001	0.009	-9999	-10000	0	0
NCOA4	0.01	0	-9999	-10000	0	0
PIAS3	0.01	0.001	-9999	-10000	0	0
cell proliferation	-0.034	0.13	-9999	-0.73	15	15
XRCC5	0.01	0.001	-9999	-10000	0	0
UBE3A	0.01	0.003	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.048	0.13	-9999	-0.33	81	81
FHL2	-0.053	0.14	-9999	-0.44	22	22
RANBP9	0.01	0.001	-9999	-10000	0	0
JMJD1A	0	0.04	-9999	-0.12	45	45
CDK6	0.007	0.04	-9999	-0.5	3	3
TGFB1I1	0.007	0.04	-9999	-0.5	3	3
T-DHT/AR/CyclinD1	-0.039	0.12	-9999	-0.33	69	69
XRCC6	0.01	0.001	-9999	-10000	0	0
T-DHT/AR	-0.038	0.14	-9999	-0.34	73	73
CTDSP1	0.01	0.001	-9999	-10000	0	0
CTDSP2	0.01	0.004	-9999	-10000	0	0
BRCA1	0.007	0.041	-9999	-0.52	3	3
TCF4	0.008	0.033	-9999	-0.5	2	2
CDKN2A	-0.15	0.24	-9999	-0.52	145	145
SRF	0.005	0.027	-9999	-10000	0	0
NKX3-1	-0.045	0.13	-9999	-0.94	6	6
KLK3	0.016	0.047	-9999	-10000	0	0
TMF1	0.01	0.001	-9999	-10000	0	0
HNRNPA1	0.01	0.002	-9999	-10000	0	0
AOF2	0	0.003	-9999	-10000	0	0
APPL1	0.018	0.004	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.039	0.12	-9999	-0.33	65	65
AR	-0.064	0.18	-9999	-0.52	64	64
UBA3	0.01	0.001	-9999	-10000	0	0
PATZ1	0.01	0.002	-9999	-10000	0	0
PAWR	0.01	0.001	-9999	-10000	0	0
PRKDC	0.01	0.001	-9999	-10000	0	0
PA2G4	0.01	0.003	-9999	-10000	0	0
UBE2I	0.01	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.031	0.11	-9999	-0.3	64	64
RPS6KA3	0.01	0.001	-9999	-10000	0	0
T-DHT/AR/ARA70	-0.035	0.12	-9999	-0.33	64	64
LATS2	0.01	0.002	-9999	-10000	0	0
T-DHT/AR/PRX1	-0.033	0.11	-9999	-0.3	64	64
Cyclin D3/CDK11 p58	0	0	-9999	-10000	0	0
VAV3	0.004	0.057	-9999	-0.5	6	6
KLK2	-0.042	0.091	-9999	-0.44	10	10
CASP8	0.009	0.023	-9999	-0.5	1	1
T-DHT/AR/TIF2/CARM1	-0.027	0.11	-9999	-0.29	68	68
TMPRSS2	-0.096	0.27	-9999	-0.98	40	40
CCND1	0.004	0.056	-9999	-0.5	6	6
PIAS1	0.01	0.003	-9999	-10000	0	0
mol:T-DHT	-0.007	0.026	-9999	-0.079	34	34
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.01	0.006	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.038	0.12	-9999	-0.33	67	67
CMTM2	-0.091	0.2	-9999	-0.5	97	97
SNURF	-0.01	0.098	-9999	-0.5	19	19
ZMIZ1	0.004	0.023	-9999	-10000	0	0
CCND3	0.01	0	-9999	-10000	0	0
TGIF1	0.01	0.002	-9999	-10000	0	0
FKBP4	0.009	0.024	-9999	-0.52	1	1

×

Syndecan-2-mediated 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
Syndecan-2/Fibronectin	0.014	0.045	-9999	-0.33	8	8
EPHB2	-0.047	0.16	-9999	-0.52	53	53
Syndecan-2/TACI	-0.01	0.092	-9999	-0.3	44	44
LAMA1	-0.018	0.12	-9999	-0.51	26	26
Syndecan-2/alpha2 ITGB1	-0.058	0.11	-9999	-0.33	16	16
HRAS	0.01	0	-9999	-10000	0	0
Syndecan-2/CASK	-0.002	0.027	-9999	-0.3	4	4
ITGA5	0.008	0.033	-9999	-0.51	2	2
BAX	0.03	0.025	-9999	-10000	0	0
EPB41	0.01	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.002	0.024	-9999	-0.26	4	4
LAMA3	-0.093	0.2	-9999	-0.5	99	99
EZR	0.01	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.096	0.21	-9999	-0.5	102	102
Syndecan-2/MMP2	0.016	0.031	-9999	-0.29	5	5
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.011	0.063	-9999	-0.36	15	15
dendrite morphogenesis	-0.019	0.1	-9999	-0.3	57	57
Syndecan-2/GM-CSF	-0.01	0.092	-9999	-0.3	44	44
determination of left/right symmetry	0.013	0.033	-9999	-0.35	4	4
Syndecan-2/PKC delta	0.017	0.028	-9999	-0.29	4	4
GNB2L1	0.01	0	-9999	-10000	0	0
MAPK3	-0.001	0.084	-9999	-0.26	44	44
MAPK1	-0.001	0.084	-9999	-0.26	44	44
Syndecan-2/RACK1	-0.002	0.022	-9999	-10000	0	0
NF1	0.01	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.013	0.033	-9999	-0.35	4	4
ITGA2	-0.006	0.091	-9999	-0.52	15	15
MAPK8	0.025	0.028	-9999	-0.28	4	4
Syndecan-2/alpha2/beta1 Integrin	-0.023	0.08	-9999	-0.29	30	30
Syndecan-2/Kininogen	-0.014	0.082	-9999	-0.3	36	36
ITGB1	0.01	0	-9999	-10000	0	0
SRC	0.027	0.023	-9999	-10000	0	0
Syndecan-2/CASK/Protein 4.1	-0.002	0.024	-9999	-0.26	4	4
extracellular matrix organization	0.017	0.028	-9999	-0.29	4	4
actin cytoskeleton reorganization	0.014	0.045	-9999	-0.33	8	8
Syndecan-2/Caveolin-2/Ras	-0.056	0.11	-9999	-10000	0	0
Syndecan-2/Laminin alpha3	-0.046	0.13	-9999	-0.29	103	103
Syndecan-2/RasGAP	-0.002	0.02	-9999	-10000	0	0
alpha5/beta1 Integrin	-0.001	0.023	-9999	-0.36	2	2
PRKCD	0.01	0	-9999	-10000	0	0
Syndecan-2 dimer	-0.019	0.1	-9999	-0.3	57	57
GO:0007205	0.003	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.032	0.022	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
SDCBP	0.01	0	-9999	-10000	0	0
TNFRSF13B	-0.033	0.14	-9999	-0.51	40	40
RASA1	0.01	0	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.011	0.063	-9999	-0.36	15	15
Syndecan-2/Synbindin	0.017	0.028	-9999	-0.29	4	4
TGFB1	0.01	0	-9999	-10000	0	0
CASP3	0.023	0.025	-9999	-0.26	4	4
FN1	0.005	0.052	-9999	-0.5	5	5
Syndecan-2/IL8	0.003	0.071	-9999	-0.3	25	25
SDC2	0.013	0.033	-9999	-0.35	4	4
KNG1	-0.03	0.13	-9999	-0.52	32	32
Syndecan-2/Neurofibromin	0.017	0.028	-9999	-0.29	4	4
TRAPPC4	0.01	0	-9999	-10000	0	0
CSF2	-0.033	0.14	-9999	-0.5	41	41
Syndecan-2/TGFB1	0.017	0.028	-9999	-0.29	4	4
Syndecan-2/Syntenin/PI-4-5-P2	-0.002	0.024	-9999	-0.26	4	4
Syndecan-2/Ezrin	-0.002	0.023	-9999	-0.26	4	4
PRKACA	0.023	0.025	-9999	-0.26	4	4
angiogenesis	0.003	0.07	-9999	-0.3	25	25
MMP2	0.009	0.024	-9999	-0.52	1	1
IL8	-0.013	0.11	-9999	-0.51	21	21
calcineurin-NFAT signaling pathway	-0.01	0.092	-9999	-0.3	44	44

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.009	0.023	-9999	-0.5	1	1
alphaV beta3 Integrin	-0.02	0.083	-9999	-0.36	27	27
PTK2	-0.037	0.11	-9999	-0.39	35	35
positive regulation of JNK cascade	-0.021	0.074	-9999	-0.29	35	35
CDC42/GDP	0.012	0.11	-9999	-0.38	35	35
Rac1/GDP	0.013	0.11	-9999	-0.38	35	35
RAP1B	0.01	0	-9999	-10000	0	0
RAP1A	0.01	0	-9999	-10000	0	0
CTNNB1	0.01	0	-9999	-10000	0	0
CDC42/GTP	-0.026	0.091	-9999	-0.35	35	35
nectin-3/I-afadin	-0.026	0.092	-9999	-0.35	36	36
RAPGEF1	0.006	0.12	-9999	-0.42	35	35
mol:GTP	0	0	-9999	-10000	0	0
CRK	-0.002	0.14	-9999	-0.48	35	35
PDGFB-D/PDGFRB	0.009	0.023	-9999	-0.5	1	1
TLN1	0.002	0.09	-9999	-0.42	15	15
Rap1/GTP	-0.022	0.078	-9999	-0.3	35	35
IQGAP1	0.01	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.026	0.092	-9999	-0.35	36	36
PVR	0.01	0	-9999	-10000	0	0
Necl-5(dimer)	0.01	0	-9999	-10000	0	0
mol:GDP	0.006	0.13	-9999	-0.46	35	35
MLLT4	0.01	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
PI3K	-0.018	0.067	-9999	-0.49	2	2
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.008	0.054	-9999	-0.37	11	11
positive regulation of lamellipodium assembly	-0.023	0.079	-9999	-0.3	36	36
PVRL1	-0.002	0.078	-9999	-0.52	11	11
PVRL3	-0.028	0.13	-9999	-0.5	36	36
PVRL2	0.01	0	-9999	-10000	0	0
PIK3R1	0.009	0.023	-9999	-0.5	1	1
CDH1	0.008	0.032	-9999	-0.5	2	2
CLDN1	-0.009	0.098	-9999	-0.51	18	18
JAM-A/CLDN1	-0.029	0.089	-9999	-0.52	4	4
SRC	-0.041	0.14	-9999	-0.54	35	35
ITGB3	-0.019	0.12	-9999	-0.51	27	27
nectin-1(dimer)/I-afadin/I-afadin	-0.008	0.054	-9999	-0.37	11	11
FARP2	0.002	0.13	-9999	-0.46	35	35
RAC1	0.01	0	-9999	-10000	0	0
CTNNA1	0.01	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.021	0.076	-9999	-0.29	36	36
nectin-1/I-afadin	-0.008	0.054	-9999	-0.37	11	11
nectin-2/I-afadin	0	0	-9999	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.028	0.089	-9999	-0.3	46	46
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0.009	0.023	-9999	-0.5	1	1
positive regulation of filopodium formation	-0.021	0.074	-9999	-0.29	35	35
alphaV/beta3 Integrin/Talin	-0.001	0.1	-9999	-0.39	17	17
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
PIP5K1C	-0.004	0.093	-9999	-0.44	15	15
VAV2	0	0.13	-9999	-0.47	36	36
RAP1/GDP	-0.026	0.091	-9999	-0.35	35	35
ITGAV	0.01	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.021	0.076	-9999	-0.29	36	36
nectin-3(dimer)/I-afadin/I-afadin	-0.026	0.092	-9999	-0.35	36	36
Rac1/GTP	-0.028	0.095	-9999	-0.36	36	36
PTPRM	-0.026	0.097	-9999	-0.48	15	15
E-cadherin/beta catenin/alpha catenin	-0.006	0.037	-9999	-10000	0	0
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.01	0	-9999	-10000	0	0

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0.04	0.11	0.36	54	-10000	0	54
KIRREL	-0.008	0.085	-10000	0	-0.5	14	14
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.04	0.11	-10000	0	-0.36	54	54
PLCG1	0.01	0	-10000	0	-10000	0	0
ARRB2	0.01	0	-10000	0	-10000	0	0
WASL	0.01	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.028	0.079	-10000	0	-10000	0	0
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.006	0.057	-10000	0	-10000	0	0
FYN	-0.011	0.076	-10000	0	-0.24	14	14
mol:Ca2+	-0.028	0.078	-10000	0	-0.25	13	13
mol:DAG	-0.028	0.079	-10000	0	-0.25	13	13
NPHS2	-0.002	0.015	-10000	0	-10000	0	0
mol:IP3	-0.028	0.079	-10000	0	-0.25	13	13
regulation of endocytosis	-0.023	0.065	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/Cholesterol	-0.029	0.081	-10000	0	-0.26	54	54
establishment of cell polarity	-0.04	0.11	-10000	0	-0.36	54	54
Nephrin/NEPH1/podocin/NCK1-2	-0.025	0.07	-10000	0	-10000	0	0
Nephrin/NEPH1/beta Arrestin2	-0.01	0.071	-10000	0	-10000	0	0
NPHS1	-0.035	0.14	-10000	0	-0.51	40	40
Nephrin/NEPH1/podocin	-0.025	0.071	-10000	0	-0.24	14	14
TJP1	0.01	0	-10000	0	-10000	0	0
NCK1	0.01	0	-10000	0	-10000	0	0
NCK2	0.01	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.028	0.079	-10000	0	-0.26	13	13
CD2AP	0.01	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.028	0.079	-10000	0	-0.26	4	4
GRB2	0.01	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.028	0.1	-10000	0	-0.26	79	79
cytoskeleton organization	0.008	0.066	-10000	0	-10000	0	0
Nephrin/NEPH1	-0.028	0.078	-10000	0	-0.25	54	54
Nephrin/NEPH1/ZO-1	-0.031	0.087	-10000	0	-0.28	54	54

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.011	0.1	-9999	-0.5	20	20
GNB1/GNG2	-0.047	0.1	-9999	-0.43	16	16
mol:DAG	-0.009	0.11	-9999	-0.39	16	16
PLCG1	-0.01	0.11	-9999	-0.4	16	16
YES1	-0.022	0.12	-9999	-0.44	16	16
FZD3	0.009	0.024	-9999	-0.52	1	1
FZD6	0.009	0.023	-9999	-0.5	1	1
G protein	-0.041	0.096	-9999	-0.41	16	16
MAP3K7	-0.017	0.12	-9999	-0.38	29	29
mol:Ca2+	-0.009	0.1	-9999	-0.38	16	16
mol:IP3	-0.009	0.11	-9999	-0.39	16	16
NLK	-0.002	0.006	-9999	-10000	0	0
GNB1	0.01	0	-9999	-10000	0	0
CAMK2A	-0.025	0.13	-9999	-0.42	30	30
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.031	0.12	-9999	-0.47	16	16
CSNK1A1	0.01	0	-9999	-10000	0	0
GNAS	-0.022	0.12	-9999	-0.44	16	16
GO:0007205	-0.009	0.1	-9999	-0.39	16	16
WNT6	-0.021	0.12	-9999	-0.52	28	28
WNT4	-0.022	0.12	-9999	-0.5	30	30
NFAT1/CK1 alpha	-0.049	0.099	-9999	-0.42	17	17
GNG2	0.008	0.032	-9999	-0.5	2	2
WNT5A	0.005	0.051	-9999	-0.5	5	5
WNT11	-0.059	0.17	-9999	-0.5	66	66
CDC42	-0.015	0.11	-9999	-0.41	16	16

×

IL12-mediated signaling 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	0.024	0.093	-10000	0	-0.35	12	12
TBX21	-0.008	0.34	-10000	0	-1.2	30	30
B2M	0.011	0.005	-10000	0	-10000	0	0
TYK2	0.017	0.015	-10000	0	-10000	0	0
IL12RB1	0.001	0.094	-10000	0	-0.52	15	15
GADD45B	0.013	0.28	-10000	0	-1	20	20
IL12RB2	-0.026	0.15	-10000	0	-0.51	41	41
GADD45G	0.014	0.27	-10000	0	-1	21	21
natural killer cell activation	0.008	0.016	-10000	0	-10000	0	0
RELB	0.01	0	-10000	0	-10000	0	0
RELA	0.01	0	-10000	0	-10000	0	0
IL18	0.005	0.07	-10000	0	-0.5	9	9
IL2RA	-0.028	0.14	-10000	0	-0.52	35	35
IFNG	-0.034	0.14	-10000	0	-0.51	40	40
STAT3 (dimer)	0.025	0.23	-10000	0	-0.79	21	21
HLA-DRB5	-0.044	0.16	-10000	0	-0.5	52	52
FASLG	0.012	0.29	-10000	0	-1	22	22
NF kappa B2 p52/RelB	-0.083	0.22	-10000	0	-0.88	25	25
CD4	0	0.072	-10000	0	-0.5	10	10
SOCS1	0.009	0.024	-10000	0	-0.52	1	1
EntrezGene:6955	0	0.008	-10000	0	-10000	0	0
CD3D	0.008	0.041	-10000	0	-0.5	3	3
CD3E	0.006	0.052	-10000	0	-0.5	5	5
CD3G	0	0.076	-10000	0	-0.5	11	11
IL12Rbeta2/JAK2	-0.004	0.11	-10000	0	-0.36	43	43
CCL3	0.016	0.27	-10000	0	-0.96	22	22
CCL4	0.015	0.28	-10000	0	-1	22	22
HLA-A	0.011	0.004	-10000	0	-10000	0	0
IL18/IL18R	0.018	0.12	-10000	0	-0.36	39	39
NOS2	-0.044	0.41	-10000	0	-1.2	50	50
IL12/IL12R/TYK2/JAK2/SPHK2	0.024	0.094	-10000	0	-0.35	12	12
IL1R1	0.016	0.28	-10000	0	-1	21	21
IL4	-0.004	0.017	-10000	0	-10000	0	0
JAK2	0.015	0.036	-10000	0	-0.5	2	2
EntrezGene:6957	0	0.008	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	0.013	0.16	-10000	0	-0.87	11	11
RAB7A	0.035	0.23	-10000	0	-0.82	15	15
lysosomal transport	0.037	0.22	-10000	0	-0.76	16	16
FOS	-0.048	0.35	-10000	0	-1.1	42	42
STAT4 (dimer)	0.034	0.26	-10000	0	-0.87	22	22
STAT5A (dimer)	-0.097	0.23	-10000	0	-0.84	31	31
GZMA	0.013	0.28	-10000	0	-1.1	21	21
GZMB	-0.001	0.32	-10000	0	-1.2	26	26
HLX	0.005	0.052	-10000	0	-0.5	5	5
LCK	0.014	0.29	-10000	0	-1	23	23
TCR/CD3/MHC II/CD4	-0.023	0.17	-10000	0	-0.55	30	30
IL2/IL2R	-0.023	0.081	-10000	0	-0.28	40	40
MAPK14	0.021	0.27	-10000	0	-0.93	22	22
CCR5	0.016	0.26	-10000	0	-1	18	18
IL1B	-0.012	0.12	-10000	0	-0.5	28	28
STAT6	0.028	0.085	-10000	0	-0.26	4	4
STAT4	0.01	0	-10000	0	-10000	0	0
STAT3	0.01	0	-10000	0	-10000	0	0
STAT1	0.01	0	-10000	0	-10000	0	0
NFKB1	0.01	0	-10000	0	-10000	0	0
NFKB2	0.01	0	-10000	0	-10000	0	0
IL12B	0.013	0.057	-10000	0	-0.53	5	5
CD8A	0.004	0.061	-10000	0	-0.5	7	7
CD8B	0.003	0.066	-10000	0	-0.5	8	8
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.024	0.093	0.34	12	-10000	0	12
IL2RB	0.008	0.032	-10000	0	-0.5	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.038	0.24	-10000	0	-0.78	22	22
IL2RG	0.005	0.051	-10000	0	-0.5	5	5
IL12	0.021	0.064	-10000	0	-0.37	11	11
STAT5A	0.009	0.023	-10000	0	-0.5	1	1
CD247	0.005	0.057	-10000	0	-0.5	6	6
IL2	0.006	0.005	-10000	0	-10000	0	0
SPHK2	0.009	0.023	-10000	0	-0.5	1	1
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.011	0.06	-10000	0	-0.51	6	6
IL12/IL12R/TYK2/JAK2	0.009	0.32	-10000	0	-1	26	26
MAP2K3	0.018	0.28	-10000	0	-0.96	21	21
RIPK2	0.01	0	-10000	0	-10000	0	0
MAP2K6	0.016	0.28	-10000	0	-0.93	23	23
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.011	0.1	-10000	0	-0.5	20	20
IL18RAP	-0.005	0.098	-10000	0	-0.5	18	18
IL12Rbeta1/TYK2	0.014	0.072	-10000	0	-0.37	15	15
EOMES	-0.007	0.14	-10000	0	-1.2	6	6
STAT1 (dimer)	0.018	0.24	-10000	0	-0.78	22	22
T cell proliferation	0.03	0.21	-10000	0	-0.68	19	19
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.008	0.1	-10000	0	-0.5	21	21
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.077	0.18	-10000	0	-0.73	21	21
ATF2	0.029	0.25	-10000	0	-0.87	20	20

×

Syndecan-3-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
CTTN	0.01	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.029	0.073	-9999	-10000	0	0
Syndecan-3/Neurocan	-0.008	0.044	-9999	-0.25	15	15
POMC	-0.014	0.11	-9999	-0.5	23	23
EGFR	-0.005	0.086	-9999	-0.51	14	14
Syndecan-3/EGFR	-0.007	0.041	-9999	-0.25	7	7
AGRP	-0.2	0.25	-9999	-0.5	203	203
NCSTN	0.01	0	-9999	-10000	0	0
PSENEN	0.009	0.024	-9999	-0.52	1	1
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.008	0.032	-9999	-0.5	2	2
APH1A	0.01	0	-9999	-10000	0	0
NCAN	-0.01	0.091	-9999	-0.52	15	15
long-term memory	-0.001	0.01	-9999	-10000	0	0
Syndecan-3/IL8	-0.011	0.05	-9999	-0.25	17	17
PSEN1	0.01	0	-9999	-10000	0	0
Src/Cortactin	0	0	-9999	-10000	0	0
FYN	0.009	0.023	-9999	-0.5	1	1
limb bud formation	0	0.004	-9999	-10000	0	0
MC4R	-0.032	0.14	-9999	-0.52	36	36
SRC	0.01	0	-9999	-10000	0	0
PTN	-0.059	0.17	-9999	-0.5	66	66
FGFR/FGF/Syndecan-3	0	0.004	-9999	-10000	0	0
neuron projection morphogenesis	-0.034	0.082	-9999	-0.44	4	4
Syndecan-3/AgRP	-0.099	0.12	-9999	-0.3	2	2
Syndecan-3/AgRP/MC4R	-0.11	0.13	-9999	-0.45	16	16
Fyn/Cortactin	-0.001	0.016	-9999	-0.35	1	1
SDC3	0	0.004	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.011	0.05	-9999	-0.25	17	17
IL8	-0.013	0.11	-9999	-0.51	21	21
Syndecan-3/Fyn/Cortactin	-0.001	0.01	-9999	-10000	0	0
Syndecan-3/CASK	0	0.004	-9999	-10000	0	0
alpha-MSH/MC4R	-0.044	0.12	-9999	-0.38	56	56
Gamma Secretase	-0.001	0.019	-9999	-10000	0	0

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	0.004	0.084	-10000	0	-0.29	33	33
ACTA1	-0.008	0.1	-10000	0	-0.36	34	34
NUMA1	0.004	0.084	-10000	0	-0.33	16	16
SPTAN1	-0.004	0.1	-10000	0	-0.36	34	34
LIMK1	-0.004	0.1	-10000	0	-0.36	34	34
BIRC3	0.004	0.057	-10000	0	-0.51	6	6
BIRC2	0.01	0	-10000	0	-10000	0	0
BAX	0.01	0	-10000	0	-10000	0	0
CASP10	-0.002	0.096	-10000	0	-0.33	36	36
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.01	0	-10000	0	-10000	0	0
PTK2	0.004	0.084	-10000	0	-0.29	33	33
DIABLO	0.01	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.004	0.1	-10000	0	-0.35	34	34
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.009	0.024	-10000	0	-0.52	1	1
GSN	-0.004	0.1	-10000	0	-0.36	34	34
MADD	0.01	0	-10000	0	-10000	0	0
TFAP2A	-0.041	0.12	-10000	0	-0.64	18	18
BID	0.004	0.057	-10000	0	-0.2	35	35
MAP3K1	0.004	0.038	-10000	0	-0.2	5	5
TRADD	0.01	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0	0.002	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.004	0.1	-10000	0	-0.36	34	34
CASP9	0.01	0	-10000	0	-10000	0	0
DNA repair	-0.002	0.028	-10000	0	-10000	0	0
neuron apoptosis	0.017	0.021	-10000	0	-0.35	1	1
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.002	0.1	-10000	0	-0.34	33	33
APAF1	0.01	0	-10000	0	-10000	0	0
CASP6	0.016	0.052	-10000	0	-0.32	1	1
TRAF2	0.01	0	-10000	0	-10000	0	0
ICAD/CAD	0.002	0.1	-10000	0	-0.34	33	33
CASP7	-0.005	0.028	0.22	6	-10000	0	6
KRT18	0.012	0.017	-10000	0	-10000	0	0
apoptosis	0.006	0.091	-10000	0	-0.52	6	6
DFFA	-0.004	0.1	-10000	0	-0.36	34	34
DFFB	-0.004	0.1	-10000	0	-0.36	34	34
PARP1	0.002	0.028	-10000	0	-10000	0	0
actin filament polymerization	-0.002	0.097	0.33	32	-10000	0	32
TNF	-0.01	0.099	-10000	0	-0.5	19	19
CYCS	0.008	0.041	-10000	0	-0.22	5	5
SATB1	0.016	0.066	-10000	0	-0.4	3	3
SLK	-0.004	0.1	-10000	0	-0.36	34	34
p15 BID/BAX	0.009	0.051	-10000	0	-0.28	5	5
CASP2	0.03	0.043	-10000	0	-10000	0	0
JNK cascade	-0.004	0.037	0.2	5	-10000	0	5
CASP3	-0.011	0.11	-10000	0	-0.38	34	34
LMNB2	0.029	0.037	-10000	0	-10000	0	0
RIPK1	0.01	0	-10000	0	-10000	0	0
CASP4	0.01	0	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	-0.003	0.029	-10000	0	-0.27	4	4
negative regulation of DNA binding	-0.041	0.12	-10000	0	-0.63	18	18
stress fiber formation	-0.004	0.1	-10000	0	-0.35	34	34
GZMB	-0.011	0.11	-10000	0	-0.4	34	34
CASP1	0.01	0.033	-10000	0	-0.31	5	5
LMNB1	0.029	0.038	-10000	0	-0.22	1	1
APP	0.017	0.021	-10000	0	-0.35	1	1
TNFRSF1A	0.01	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.008	0.017	-10000	0	-0.36	1	1
VIM	0.002	0.089	-10000	0	-0.3	33	33
LMNA	0.029	0.037	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.025	0.045	-10000	0	-10000	0	0
LRDD	0.008	0.032	-10000	0	-0.5	2	2
SREBF1	-0.004	0.1	-10000	0	-0.36	34	34
APAF-1/Caspase 9	-0.003	0.016	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0.004	0.083	-10000	0	-0.28	33	33
CFL2	0.002	0.099	-10000	0	-0.34	32	32
GAS2	-0.018	0.12	-10000	0	-0.37	35	35
positive regulation of apoptosis	0.032	0.037	-10000	0	-10000	0	0
PRF1	-0.014	0.11	-10000	0	-0.5	23	23

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.009	0.023	-10000	0	-0.5	1	1
Jak2/Leptin Receptor	-0.038	0.094	0.18	1	-0.36	19	20
PTP1B/AKT1	0.011	0.037	-10000	0	-0.22	1	1
FYN	0.009	0.023	-10000	0	-0.5	1	1
p210 bcr-abl/PTP1B	0.006	0.041	-10000	0	-0.23	2	2
EGFR	-0.006	0.087	-10000	0	-0.51	14	14
EGF/EGFR	-0.049	0.09	-10000	0	-0.29	20	20
CSF1	0.005	0.051	-10000	0	-0.5	5	5
AKT1	0.01	0.001	-10000	0	-10000	0	0
INSR	0.01	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.019	0.094	-10000	0	-0.26	56	56
Insulin Receptor/Insulin	-0.006	0.021	-10000	0	-10000	0	0
HCK	-0.012	0.1	-10000	0	-0.5	21	21
CRK	0.01	0	-10000	0	-10000	0	0
TYK2	0.012	0.039	-10000	0	-0.23	1	1
EGF	-0.088	0.2	-10000	0	-0.51	92	92
YES1	0.01	0	-10000	0	-10000	0	0
CAV1	-0.092	0.096	-10000	0	-0.25	72	72
TXN	0.006	0.033	-10000	0	-0.51	2	2
PTP1B/IRS1/GRB2	0.016	0.039	-10000	0	-0.3	1	1
cell migration	-0.006	0.041	0.23	2	-10000	0	2
STAT3	0.01	0.001	-10000	0	-10000	0	0
PRLR	-0.054	0.17	-10000	0	-0.51	60	60
ITGA2B	-0.043	0.16	-10000	0	-0.5	50	50
CSF1R	0.003	0.06	-10000	0	-0.5	7	7
Prolactin Receptor/Prolactin	-0.054	0.13	-10000	0	-0.38	71	71
FGR	-0.029	0.14	-10000	0	-0.5	37	37
PTP1B/p130 Cas	0.011	0.04	-10000	0	-0.25	2	2
Crk/p130 Cas	0.016	0.039	-10000	0	-0.26	1	1
DOK1	0.017	0.038	-10000	0	-0.25	1	1
JAK2	-0.005	0.066	-10000	0	-0.3	13	13
Jak2/Leptin Receptor/Leptin	-0.027	0.067	-10000	0	-0.41	5	5
PIK3R1	0.009	0.023	-10000	0	-0.5	1	1
PTPN1	0.006	0.041	-10000	0	-0.23	2	2
LYN	0.01	0	-10000	0	-10000	0	0
CDH2	-0.049	0.17	-10000	0	-0.52	55	55
SRC	0.015	0.018	-10000	0	-10000	0	0
ITGB3	-0.02	0.12	-10000	0	-0.51	27	27
CAT1/PTP1B	-0.03	0.13	-10000	0	-0.48	22	22
CAPN1	0.01	0.001	-10000	0	-10000	0	0
CSK	0.01	0	-10000	0	-10000	0	0
PI3K	-0.003	0.02	-10000	0	-10000	0	0
mol:H2O2	-0.001	0.002	-10000	0	-10000	0	0
STAT3 (dimer)	-0.023	0.065	-10000	0	-0.42	5	5
negative regulation of transcription	-0.005	0.065	-10000	0	-0.29	13	13
FCGR2A	0.001	0.068	-10000	0	-0.5	9	9
FER	0.008	0.004	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.056	0.13	-10000	0	-0.36	76	76
BLK	-0.075	0.19	-10000	0	-0.52	79	79
Insulin Receptor/Insulin/Shc	-0.001	0.014	-10000	0	-0.31	1	1
RHOA	0.01	0.001	-10000	0	-10000	0	0
LEPR	-0.042	0.15	-10000	0	-0.5	50	50
BCAR1	0.009	0.023	-10000	0	-0.5	1	1
p210 bcr-abl/Grb2	0.01	0	-10000	0	-10000	0	0
mol:NADPH	0	0.002	-10000	0	-10000	0	0
TRPV6	-0.039	0.14	-10000	0	-0.54	22	22
PRL	-0.011	0.084	-10000	0	-0.52	13	13
SOCS3	0	0.11	-10000	0	-1.2	4	4
SPRY2	0.007	0.023	-10000	0	-0.5	1	1
Insulin Receptor/Insulin/IRS1	-0.001	0.014	-10000	0	-0.3	1	1
CSF1/CSF1R	0.011	0.061	-10000	0	-0.36	6	6
Ras protein signal transduction	0.01	0.014	-10000	0	-10000	0	0
IRS1	0.009	0.023	-10000	0	-0.5	1	1
INS	0	0.001	-10000	0	-10000	0	0
LEP	-0.045	0.16	-10000	0	-0.52	50	50
STAT5B	0.004	0.044	-10000	0	-0.23	2	2
STAT5A	0.004	0.045	-10000	0	-0.23	3	3
GRB2	0.01	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.011	0.041	-10000	0	-0.26	2	2
CSN2	-0.015	0.045	-10000	0	-10000	0	0
PIK3CA	0.01	0	-10000	0	-10000	0	0
LAT	0.006	0.066	-10000	0	-0.45	9	9
YBX1	0.016	0.001	-10000	0	-10000	0	0
LCK	0.007	0.04	-10000	0	-0.5	3	3
SHC1	0.009	0.024	-10000	0	-0.52	1	1
NOX4	-0.01	0.096	-10000	0	-0.51	17	17

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.01	0	-10000	0	-10000	0	0
HDAC4	0.009	0.024	-10000	0	-0.52	1	1
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.005	0.088	0.37	27	-10000	0	27
CDKN1A	-0.001	0.031	-10000	0	-0.68	1	1
KAT2B	0.01	0	-10000	0	-10000	0	0
BAX	0.01	0	-10000	0	-10000	0	0
FOXO3	0	0	-10000	0	-10000	0	0
FOXO1	0.01	0	-10000	0	-10000	0	0
FOXO4	0.018	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.01	0	-10000	0	-10000	0	0
TAT	-0.038	0.15	-10000	0	-0.52	44	44
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.007	0.03	-10000	0	-0.37	3	3
PPARGC1A	-0.11	0.22	-10000	0	-0.5	119	119
FHL2	-0.061	0.18	-10000	0	-0.52	66	66
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0	0.006	-10000	0	-10000	0	0
HIST2H4A	-0.005	0.088	-10000	0	-0.37	27	27
SIRT1/FOXO3a	0	0.006	-10000	0	-10000	0	0
SIRT1	0	0.008	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0	0.015	-10000	0	-0.3	1	1
SIRT1/Histone H1b	-0.01	0.034	-10000	0	-10000	0	0
apoptosis	0	0.006	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.072	0.13	-10000	0	-0.3	119	119
p53/SIRT1	0.001	0.017	0.38	1	-10000	0	1
SIRT1/FOXO4	0	0.007	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	-0.037	0.095	-10000	0	-0.28	66	66
HIST1H1E	0.003	0.047	-10000	0	-10000	0	0
SIRT1/p300	0	0.006	-10000	0	-10000	0	0
muscle cell differentiation	0.002	0.025	0.3	3	-10000	0	3
TP53	0	0.008	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0	0.006	-10000	0	-10000	0	0
CREBBP	0.01	0	-10000	0	-10000	0	0
MEF2D	0.01	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.033	0.11	-10000	0	-0.37	44	44
ACSS2	0.015	0.018	-10000	0	-0.35	1	1
SIRT1/PCAF/MYOD	-0.002	0.025	-10000	0	-0.3	3	3

×

FAS signaling pathway (CD95)

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
SPTAN1	0.001	0.019	0.2	2	-10000	0	2
RFC1	0.001	0.019	0.2	2	-10000	0	2
PRKDC	0.001	0.019	0.2	2	-10000	0	2
RIPK1	0.012	0.004	-10000	0	-10000	0	0
CASP7	-0.016	0.04	0.23	1	-0.5	1	2
FASLG/FAS/FADD/FAF1	0.006	0.073	0.21	34	-0.26	8	42
MAP2K4	-0.024	0.13	-10000	0	-0.46	7	7
mol:ceramide	-0.008	0.091	-10000	0	-0.37	10	10
GSN	0.001	0.019	0.21	1	-10000	0	1
FASLG/FAS/FADD/FAF1/Caspase 8	0.012	0.076	0.29	1	-0.33	8	9
FAS	0.004	0.047	-10000	0	-0.51	4	4
BID	0.001	0.02	0.28	1	-0.3	1	2
MAP3K1	-0.006	0.081	0.19	1	-0.32	4	5
MAP3K7	0.008	0.004	-10000	0	-10000	0	0
RB1	0.001	0.019	0.2	2	-10000	0	2
CFLAR	0.012	0.004	-10000	0	-10000	0	0
HGF/MET	-0.064	0.14	-10000	0	-0.34	91	91
ARHGDIB	0.001	0.019	0.2	2	-10000	0	2
FADD	0.008	0.005	-10000	0	-10000	0	0
actin filament polymerization	-0.001	0.019	-10000	0	-0.21	1	1
NFKB1	-0.046	0.084	-10000	0	-0.26	6	6
MAPK8	-0.055	0.2	-10000	0	-0.42	112	112
DFFA	0.001	0.019	0.2	2	-10000	0	2
DNA fragmentation during apoptosis	0.001	0.019	0.2	2	-10000	0	2
FAS/FADD/MET	-0.021	0.077	-10000	0	-0.3	35	35
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	0.007	0.047	-10000	0	-0.51	4	4
FAF1	0.009	0.005	-10000	0	-10000	0	0
PARP1	0.001	0.019	0.2	2	-10000	0	2
DFFB	0.001	0.019	0.2	2	-10000	0	2
CHUK	-0.041	0.074	-10000	0	-10000	0	0
FASLG	0.001	0.062	-10000	0	-0.51	7	7
FAS/FADD	-0.005	0.033	-10000	0	-0.36	4	4
HGF	-0.018	0.12	-10000	0	-0.5	27	27
LMNA	0.001	0.018	0.2	1	-10000	0	1
CASP6	0.001	0.019	0.2	2	-10000	0	2
CASP10	0.006	0.033	-10000	0	-0.51	2	2
CASP3	0.002	0.023	0.21	4	-0.23	1	5
PTPN13	-0.042	0.15	-10000	0	-0.5	50	50
CASP8	0.001	0.028	0.24	4	-0.36	1	5
IL6	-0.24	0.51	-10000	0	-1.2	111	111
MET	-0.023	0.13	-10000	0	-0.51	31	31
ICAD/CAD	0.001	0.018	0.2	1	-10000	0	1
FASLG/FAS/FADD/FAF1/Caspase 10	-0.008	0.092	-10000	0	-0.38	10	10
activation of caspase activity by cytochrome c	0.001	0.02	0.28	1	-0.3	1	2
PAK2	0.001	0.019	0.2	2	-10000	0	2
BCL2	0.007	0.041	-10000	0	-0.51	3	3

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.038	0.11	-10000	0	-0.32	57	57
cell-cell adhesion	0.049	0.097	0.42	12	-10000	0	12
Ephrin B/EPHB2/RasGAP	-0.034	0.088	-10000	0	-0.49	2	2
ITSN1	0.01	0	-10000	0	-10000	0	0
PIK3CA	0.01	0	-10000	0	-10000	0	0
SHC1	0.009	0.024	-10000	0	-0.52	1	1
Ephrin B1/EPHB3	-0.009	0.051	-10000	0	-0.31	14	14
Ephrin B1/EPHB1	-0.037	0.1	-10000	0	-0.32	58	58
HRAS/GDP	-0.035	0.085	-10000	0	-0.52	4	4
Ephrin B/EPHB1/GRB7	-0.039	0.1	-10000	0	-0.54	6	6
Endophilin/SYNJ1	-0.006	0.092	-10000	0	-0.46	2	2
KRAS	0.009	0.024	-10000	0	-0.52	1	1
Ephrin B/EPHB1/Src	-0.036	0.095	-10000	0	-0.55	4	4
endothelial cell migration	-0.004	0.032	-10000	0	-10000	0	0
GRB2	0.01	0	-10000	0	-10000	0	0
GRB7	0.004	0.057	-10000	0	-0.51	6	6
PAK1	-0.002	0.096	-10000	0	-0.46	3	3
HRAS	0.01	0	-10000	0	-10000	0	0
RRAS	-0.008	0.098	-10000	0	-0.47	4	4
DNM1	0.003	0.058	-10000	0	-0.52	6	6
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.008	0.1	-10000	0	-0.53	4	4
lamellipodium assembly	-0.049	0.097	-10000	0	-0.42	12	12
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.007	0.071	-10000	0	-0.46	4	4
PIK3R1	0.009	0.023	-10000	0	-0.5	1	1
EPHB2	-0.047	0.16	-10000	0	-0.52	53	53
EPHB3	-0.002	0.078	-10000	0	-0.52	11	11
EPHB1	-0.05	0.17	-10000	0	-0.52	56	56
EPHB4	0.01	0	-10000	0	-10000	0	0
mol:GDP	-0.032	0.085	-10000	0	-0.4	9	9
Ephrin B/EPHB2	-0.035	0.09	-10000	0	-0.26	57	57
Ephrin B/EPHB3	-0.013	0.06	-10000	0	-0.27	24	24
JNK cascade	-0.031	0.12	-10000	0	-0.5	9	9
Ephrin B/EPHB1	-0.037	0.097	-10000	0	-0.27	58	58
RAP1/GDP	-0.026	0.074	-10000	0	-0.47	4	4
EFNB2	0.002	0.065	-10000	0	-0.5	8	8
EFNB3	0.006	0.047	-10000	0	-0.51	4	4
EFNB1	0.007	0.04	-10000	0	-0.5	3	3
Ephrin B2/EPHB1-2	-0.066	0.13	-10000	0	-0.3	107	107
RAP1B	0.01	0	-10000	0	-10000	0	0
RAP1A	0.01	0	-10000	0	-10000	0	0
CDC42/GTP	-0.048	0.098	-10000	0	-0.44	12	12
Rap1/GTP	-0.049	0.097	-10000	0	-0.43	12	12
axon guidance	-0.038	0.11	-10000	0	-0.32	57	57
MAPK3	0.019	0.064	-10000	0	-0.41	4	4
MAPK1	0.019	0.064	-10000	0	-0.41	4	4
Rac1/GDP	0.002	0.09	-10000	0	-0.49	4	4
actin cytoskeleton reorganization	-0.04	0.079	-10000	0	-0.35	12	12
CDC42/GDP	0.002	0.09	-10000	0	-0.49	4	4
PI3K	-0.004	0.032	-10000	0	-10000	0	0
EFNA5	0.002	0.062	-10000	0	-0.51	7	7
Ephrin B2/EPHB4	-0.005	0.038	-10000	0	-0.3	8	8
Ephrin B/EPHB2/Intersectin/N-WASP	0.006	0.064	-10000	0	-0.46	2	2
CDC42	0.01	0	-10000	0	-10000	0	0
RAS family/GTP	-0.048	0.095	-10000	0	-0.42	12	12
PTK2	0.015	0.028	-10000	0	-10000	0	0
MAP4K4	-0.032	0.13	-10000	0	-0.5	9	9
SRC	0.01	0	-10000	0	-10000	0	0
KALRN	0.007	0.04	-10000	0	-0.5	3	3
Intersectin/N-WASP	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.009	0.095	-10000	0	-0.32	13	13
MAP2K1	0.013	0.067	-10000	0	-0.43	4	4
WASL	0.01	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.062	0.12	-10000	0	-0.29	103	103
cell migration	0.019	0.07	-10000	0	-0.47	4	4
NRAS	0.01	0	-10000	0	-10000	0	0
SYNJ1	-0.006	0.094	-10000	0	-0.46	2	2
PXN	0.01	0	-10000	0	-10000	0	0
TF	-0.065	0.14	-10000	0	-0.48	19	19
HRAS/GTP	-0.053	0.1	-10000	0	-0.45	12	12
Ephrin B1/EPHB1-2	-0.063	0.13	-10000	0	-0.3	103	103
cell adhesion mediated by integrin	0.003	0.054	0.3	11	-10000	0	11
RAC1	0.01	0	-10000	0	-10000	0	0
mol:GTP	-0.057	0.11	-10000	0	-0.49	12	12
RAC1-CDC42/GTP	-0.053	0.1	-10000	0	-0.44	14	14
RASA1	0.01	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.026	0.074	-10000	0	-0.47	4	4
ruffle organization	-0.01	0.12	-10000	0	-0.43	12	12
NCK1	0.01	0	-10000	0	-10000	0	0
receptor internalization	-0.003	0.094	-10000	0	-0.44	3	3
Ephrin B/EPHB2/KALRN	-0.036	0.091	-10000	0	-0.49	3	3
ROCK1	0.012	0.049	-10000	0	-0.27	14	14
RAS family/GDP	-0.037	0.075	-10000	0	-0.34	11	11
Rac1/GTP	-0.052	0.1	-10000	0	-0.45	12	12
Ephrin B/EPHB1/Src/Paxillin	0.004	0.072	-10000	0	-0.31	12	12

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.02	0.083	-9999	-0.36	27	27
AKT1	0.028	0.12	-9999	-0.52	13	13
PTK2B	-0.011	0.13	-9999	-0.57	14	14
VEGFR2 homodimer/Frs2	-0.023	0.14	-9999	-0.7	12	12
CAV1	-0.32	0.24	-9999	-0.5	313	313
CALM1	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.042	0.12	-9999	-0.64	12	12
endothelial cell proliferation	0.034	0.12	-9999	-0.5	13	13
mol:Ca2+	0.002	0.12	-9999	-0.56	13	13
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.038	0.11	-9999	-0.59	12	12
RP11-342D11.1	-0.004	0.12	-9999	-0.56	13	13
CDH5	-0.058	0.17	-9999	-0.5	65	65
VEGFA homodimer	0	0	-9999	-10000	0	0
SHC1	0.009	0.024	-9999	-0.52	1	1
SHC2	0.001	0.069	-9999	-0.5	9	9
HRAS/GDP	-0.031	0.091	-9999	-0.48	13	13
SH2D2A	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.033	0.098	-9999	-0.49	15	15
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.041	0.12	-9999	-0.62	12	12
VEGFR1 homodimer	0.01	0	-9999	-10000	0	0
SHC/GRB2/SOS1	-0.034	0.1	-9999	-0.52	13	13
GRB10	0.003	0.12	-9999	-0.56	13	13
PTPN11	0.01	0	-9999	-10000	0	0
GRB2	0.01	0	-9999	-10000	0	0
PAK1	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.066	0.16	-9999	-0.55	36	36
HRAS	0.01	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	0.005	0.085	-9999	-0.35	13	13
HIF1A	0.01	0	-9999	-10000	0	0
FRS2	0.008	0.034	-9999	-0.52	2	2
oxygen and reactive oxygen species metabolic process	-0.038	0.11	-9999	-0.58	12	12
mol:GTP	0	0	-9999	-10000	0	0
FLT4	-0.004	0.082	-9999	-0.5	13	13
Nck/Pak	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.042	0.12	-9999	-0.62	12	12
mol:GDP	-0.033	0.097	-9999	-0.51	13	13
mol:NADP	0.023	0.11	-9999	-0.42	17	17
eNOS/Hsp90	0.027	0.1	-9999	-0.41	14	14
PIK3R1	0.009	0.023	-9999	-0.5	1	1
mol:IP3	0.002	0.12	-9999	-0.56	13	13
HIF1A/ARNT	0	0	-9999	-10000	0	0
SHB	0.009	0.023	-9999	-0.5	1	1
VEGFA	0.012	0	-9999	-10000	0	0
VEGFC	0.007	0.04	-9999	-0.5	3	3
FAK1/Vinculin	0.004	0.14	-9999	-0.6	14	14
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.051	0.12	-9999	-0.6	13	13
PTPN6	0.01	0	-9999	-10000	0	0
EPAS1	-0.049	0.17	-9999	-0.48	65	65
mol:L-citrulline	0.023	0.11	-9999	-0.42	17	17
ITGAV	0.01	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.039	0.11	-9999	-0.61	12	12
VEGFR2 homodimer/VEGFA homodimer	-0.041	0.12	-9999	-0.61	13	13
VEGFR2/3 heterodimer	-0.029	0.16	-9999	-0.69	17	17
VEGFB	0.01	0	-9999	-10000	0	0
MAPK11	0.003	0.13	-9999	-0.56	14	14
VEGFR2 homodimer	-0.03	0.16	-9999	-0.42	65	65
FLT1	0.01	0	-9999	-10000	0	0
NEDD4	0.011	0.023	-9999	-0.5	1	1
MAPK3	0.007	0.12	-9999	-0.53	13	13
MAPK1	0.007	0.12	-9999	-0.53	13	13
VEGFA145/NRP2	-0.002	0.027	-9999	-0.35	3	3
VEGFR1/2 heterodimer	-0.022	0.14	-9999	-0.68	12	12
KDR	-0.03	0.16	-9999	-0.42	65	65
VEGFA165/NRP1/VEGFR2 homodimer	-0.038	0.11	-9999	-0.56	14	14
SRC	0.01	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.008	0.12	-9999	-0.54	13	13
PI3K	-0.037	0.11	-9999	-0.57	14	14
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.041	0.12	-9999	-0.62	12	12
FES	0.002	0.12	-9999	-0.57	13	13
GAB1	-0.04	0.11	-9999	-0.58	14	14
VEGFR2 homodimer/VEGFA homodimer/Src	-0.041	0.12	-9999	-0.62	12	12
CTNNB1	0.01	0	-9999	-10000	0	0
SOS1	0.01	0	-9999	-10000	0	0
ARNT	0.01	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.11	0.14	-9999	-0.4	53	53
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.041	0.12	-9999	-0.62	12	12
PI3K/GAB1	0.026	0.12	-9999	-0.52	14	14
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.037	0.11	-9999	-0.58	12	12
PRKACA	0.01	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.05	0.14	-9999	-0.63	18	18
HSP90AA1	0.01	0	-9999	-10000	0	0
CDC42	0.002	0.12	-9999	-0.57	13	13
actin cytoskeleton reorganization	-0.041	0.12	-9999	-0.62	12	12
PTK2	-0.002	0.14	-9999	-0.65	14	14
EDG1	-0.004	0.12	-9999	-0.56	13	13
mol:DAG	0.002	0.12	-9999	-0.56	13	13
CaM/Ca2+	-0.034	0.099	-9999	-0.52	13	13
MAP2K3	0.009	0.12	-9999	-0.54	13	13
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.038	0.11	-9999	-0.58	13	13
PLCG1	0.002	0.12	-9999	-0.57	13	13
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.039	0.11	-9999	-0.58	13	13
IQGAP1	0.01	0	-9999	-10000	0	0
YES1	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.041	0.12	-9999	-0.62	12	12
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.041	0.12	-9999	-0.62	12	12
cell migration	0.01	0.14	-9999	-0.58	13	13
mol:PI-3-4-5-P3	-0.035	0.1	-9999	-0.52	14	14
FYN	0.009	0.023	-9999	-0.5	1	1
VEGFB/NRP1	0.002	0.12	-9999	-0.53	13	13
mol:NO	0.023	0.11	-9999	-0.42	17	17
PXN	0.01	0	-9999	-10000	0	0
HRAS/GTP	-0.031	0.09	-9999	-0.48	13	13
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.001	0.12	-9999	-0.58	13	13
VHL	0.01	0	-9999	-10000	0	0
ITGB3	-0.019	0.12	-9999	-0.51	27	27
NOS3	0.022	0.12	-9999	-0.47	17	17
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.046	0.13	-9999	-0.63	15	15
RAC1	0.01	0	-9999	-10000	0	0
PRKCA	0.008	0.12	-9999	-0.52	13	13
PRKCB	0.003	0.13	-9999	-0.56	15	15
VCL	0.01	0	-9999	-10000	0	0
VEGFA165/NRP1	-0.004	0.12	-9999	-0.56	13	13
VEGFR1/2 heterodimer/VEGFA homodimer	-0.041	0.12	-9999	-0.62	12	12
VEGFA165/NRP2	-0.002	0.027	-9999	-0.35	3	3
MAPKKK cascade	-0.03	0.089	-9999	-0.48	12	12
NRP2	0.007	0.04	-9999	-0.5	3	3
VEGFC homodimer	0.007	0.04	-9999	-0.5	3	3
NCK1	0.01	0	-9999	-10000	0	0
ROCK1	0.01	0	-9999	-10000	0	0
FAK1/Paxillin	0.004	0.14	-9999	-0.6	14	14
MAP3K13	0.002	0.12	-9999	-0.57	13	13
PDPK1	0.025	0.11	-9999	-0.48	13	13

×

LPA receptor mediated 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
GNB1/GNG2	-0.001	0.018	-9999	-0.25	2	2
NF kappa B1 p50/RelA/I kappa B alpha	-0.025	0.068	-9999	-0.36	3	3
AP1	-0.039	0.087	-9999	-0.45	4	4
mol:PIP3	-0.028	0.073	-9999	-0.48	3	3
AKT1	-0.002	0.014	-9999	-10000	0	0
PTK2B	0.018	0.032	-9999	-0.27	2	2
RHOA	0.025	0.024	-9999	-10000	0	0
PIK3CB	0.01	0	-9999	-10000	0	0
mol:Ca2+	0.005	0.085	-9999	-0.37	4	4
MAGI3	0.004	0.056	-9999	-0.5	6	6
RELA	0.01	0	-9999	-10000	0	0
apoptosis	-0.005	0.083	-9999	-0.25	46	46
HRAS/GDP	0	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.015	0.064	-9999	-0.26	8	8
NF kappa B1 p50/RelA	-0.025	0.07	-9999	-0.38	2	2
endothelial cell migration	0.022	0.021	-9999	-0.44	1	1
ADCY4	0.011	0.069	-9999	-0.36	5	5
ADCY5	-0.002	0.084	-9999	-0.29	18	18
ADCY6	0.02	0.052	-9999	-0.35	1	1
ADCY7	0.019	0.052	-9999	-0.35	1	1
ADCY1	0.018	0.058	-9999	-0.3	4	4
ADCY2	0.004	0.075	-9999	-0.3	11	11
ADCY3	0.02	0.051	-9999	-0.35	1	1
ADCY8	-0.055	0.1	-9999	-0.3	21	21
ADCY9	0.016	0.061	-9999	-0.33	5	5
GSK3B	0.024	0.03	-9999	-0.25	2	2
arachidonic acid secretion	0.024	0.049	-9999	-0.31	1	1
GNG2	0.008	0.032	-9999	-0.5	2	2
TRIP6	0.017	0.03	-9999	-0.36	3	3
GNAO1	0.018	0.037	-9999	-0.3	6	6
HRAS	0.01	0	-9999	-10000	0	0
NFKBIA	0.012	0.095	-9999	-0.41	3	3
GAB1	0.007	0.04	-9999	-0.5	3	3
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.021	0.14	-9999	-0.87	12	12
JUN	0.006	0.046	-9999	-0.5	4	4
LPA/LPA2/NHERF2	-0.004	0.035	-9999	-0.3	7	7
TIAM1	-0.025	0.16	-9999	-1	12	12
PIK3R1	0.009	0.023	-9999	-0.5	1	1
mol:IP3	0.004	0.086	-9999	-0.38	4	4
PLCB3	0.019	0.034	-9999	-0.26	7	7
FOS	-0.023	0.13	-9999	-0.5	32	32
positive regulation of mitosis	0.024	0.049	-9999	-0.31	1	1
LPA/LPA1-2-3	-0.028	0.08	-9999	-0.26	52	52
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.009	0.023	-9999	-0.5	1	1
stress fiber formation	0.017	0.051	-9999	-10000	0	0
GNAZ	-0.004	0.087	-9999	-0.29	41	41
EGFR/PI3K-beta/Gab1	-0.029	0.076	-9999	-0.5	3	3
positive regulation of dendritic cell cytokine production	-0.028	0.079	-9999	-0.26	52	52
LPA/LPA2/MAGI-3	-0.004	0.035	-9999	-0.3	7	7
ARHGEF1	0.03	0.014	-9999	-10000	0	0
GNAI2	0.022	0.01	-9999	-10000	0	0
GNAI3	0.022	0.01	-9999	-10000	0	0
GNAI1	0.021	0.022	-9999	-0.29	2	2
LPA/LPA3	-0.037	0.11	-9999	-0.36	51	51
LPA/LPA2	-0.001	0.017	-9999	-0.37	1	1
LPA/LPA1	0	0.011	-9999	-0.24	1	1
HB-EGF/EGFR	-0.11	0.18	-9999	-0.33	177	177
HBEGF	-0.12	0.19	-9999	-0.38	172	172
mol:DAG	0.004	0.086	-9999	-0.38	4	4
cAMP biosynthetic process	0.006	0.061	-9999	-0.37	1	1
NFKB1	0.01	0	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
GNB1	0.01	0	-9999	-10000	0	0
LYN	0.012	0.095	-9999	-0.41	3	3
GNAQ	-0.01	0.087	-9999	-0.26	52	52
LPAR2	0.009	0.024	-9999	-0.52	1	1
LPAR3	-0.044	0.16	-9999	-0.5	51	51
LPAR1	0.013	0.007	-9999	-10000	0	0
IL8	-0.043	0.14	-9999	-0.38	32	32
PTK2	0.003	0.082	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.005	0.083	-9999	-0.25	46	46
EGFR	-0.005	0.086	-9999	-0.51	14	14
PLCG1	-0.007	0.096	-9999	-0.28	47	47
PLD2	0.003	0.082	-9999	-10000	0	0
G12/G13	0	0.007	-9999	-10000	0	0
PI3K-beta	-0.002	0.016	-9999	-10000	0	0
cell migration	-0.014	0.046	-9999	-0.25	12	12
SLC9A3R2	0.004	0.056	-9999	-0.5	6	6
PXN	0.017	0.051	-9999	-10000	0	0
HRAS/GTP	0.024	0.05	-9999	-0.32	1	1
RAC1	0.01	0	-9999	-10000	0	0
MMP9	-0.097	0.21	-9999	-0.52	99	99
PRKCE	0.005	0.051	-9999	-0.5	5	5
PRKCD	0.01	0.083	-9999	-0.35	4	4
Gi(beta/gamma)	0.022	0.052	-9999	-0.34	1	1
mol:LPA	0.003	0.007	-9999	-0.15	1	1
TRIP6/p130 Cas/FAK1/Paxillin	-0.022	0.063	-9999	-10000	0	0
MAPKKK cascade	0.024	0.049	-9999	-0.31	1	1
contractile ring contraction involved in cytokinesis	0.024	0.024	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.017	0.098	-9999	-0.26	64	64
GNA15	-0.009	0.084	-9999	-0.25	52	52
GNA12	0.01	0	-9999	-10000	0	0
GNA13	0.01	0	-9999	-10000	0	0
MAPT	0.015	0.066	-9999	-0.27	8	8
GNA11	-0.01	0.089	-9999	-0.26	52	52
Rac1/GTP	-0.022	0.14	-9999	-0.93	12	12
MMP2	0.022	0.021	-9999	-0.45	1	1

×

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

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
MAP4K1	0.019	0.097	-10000	0	-0.4	21	21
CRKL	0.016	0.097	-10000	0	-0.42	21	21
HRAS	0.028	0.1	-10000	0	-0.47	10	10
mol:PIP3	0.005	0.092	0.22	2	-0.41	20	22
SPRED1	0.01	0	-10000	0	-10000	0	0
SPRED2	0.01	0	-10000	0	-10000	0	0
GAB1	0.01	0.1	-10000	0	-0.44	21	21
FOXO3	0.021	0.087	-10000	0	-0.38	20	20
AKT1	0.015	0.094	-10000	0	-0.42	20	20
BAD	0.021	0.087	-10000	0	-0.38	20	20
megakaryocyte differentiation	-0.012	0.13	-10000	0	-0.46	26	26
GSK3B	0.021	0.087	-10000	0	-0.38	20	20
RAF1	0.034	0.085	-10000	0	-0.38	10	10
SHC1	0.009	0.024	-10000	0	-0.52	1	1
STAT3	0.011	0.099	-10000	0	-0.45	20	20
STAT1	0.008	0.21	-10000	0	-0.95	21	21
HRAS/SPRED1	-0.019	0.071	-10000	0	-0.38	10	10
cell proliferation	0.012	0.098	-10000	0	-0.44	20	20
PIK3CA	0.01	0	-10000	0	-10000	0	0
TEC	0.01	0	-10000	0	-10000	0	0
RPS6KB1	0.011	0.1	-10000	0	-0.45	20	20
HRAS/SPRED2	-0.019	0.071	-10000	0	-0.38	10	10
LYN/TEC/p62DOK	-0.019	0.085	-10000	0	-0.41	20	20
MAPK3	0.038	0.064	-10000	0	-0.27	8	8
STAP1	0.004	0.11	-10000	0	-0.45	23	23
GRAP2	-0.006	0.088	-10000	0	-0.5	15	15
JAK2	-0.039	0.17	-10000	0	-0.8	22	22
STAT1 (dimer)	0.009	0.2	-10000	0	-0.93	21	21
mol:Gleevec	-0.002	0.004	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.022	0.088	-10000	0	-0.41	21	21
actin filament polymerization	0.011	0.098	-10000	0	-0.44	20	20
LYN	0.01	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	0.011	0.14	-10000	0	-0.59	23	23
PIK3R1	0.009	0.023	-10000	0	-0.5	1	1
CBL/CRKL/GRB2	-0.018	0.079	-10000	0	-0.38	20	20
PI3K	0.02	0.096	-10000	0	-0.42	20	20
PTEN	0.01	0	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	0.005	0.25	-10000	0	-1.2	20	20
MAPK8	0.011	0.099	-10000	0	-0.45	20	20
STAT3 (dimer)	0.012	0.098	-10000	0	-0.44	20	20
positive regulation of transcription	0.036	0.054	-10000	0	-0.22	8	8
mol:GDP	-0.025	0.092	-10000	0	-0.4	23	23
PIK3C2B	0.01	0.1	-10000	0	-0.46	20	20
CBL/CRKL	0.021	0.092	-10000	0	-0.39	21	21
FER	0.011	0.099	-10000	0	-0.45	20	20
SH2B3	0.01	0.1	-10000	0	-0.45	21	21
PDPK1	0.011	0.085	-10000	0	-0.38	20	20
SNAI2	0.009	0.11	-10000	0	-0.47	21	21
positive regulation of cell proliferation	0.013	0.16	-10000	0	-0.72	21	21
KITLG	0.009	0.049	-10000	0	-0.52	4	4
cell motility	0.013	0.16	-10000	0	-0.72	21	21
PTPN6	0.002	0.007	-10000	0	-10000	0	0
EPOR	0.031	0.064	-10000	0	-10000	0	0
STAT5A (dimer)	0.015	0.14	-10000	0	-0.61	20	20
SOCS1	0.009	0.024	-10000	0	-0.52	1	1
cell migration	-0.001	0.11	0.45	21	-10000	0	21
SOS1	0.01	0	-10000	0	-10000	0	0
EPO	0.004	0.048	-10000	0	-0.52	4	4
VAV1	0.005	0.051	-10000	0	-0.5	5	5
GRB10	0.011	0.099	-10000	0	-0.45	20	20
PTPN11	0.009	0.004	-10000	0	-10000	0	0
SCF/KIT	0.005	0.1	-10000	0	-0.46	21	21
GO:0007205	-0.002	0.005	-10000	0	-10000	0	0
MAP2K1	0.037	0.069	-10000	0	-0.3	8	8
CBL	0.01	0	-10000	0	-10000	0	0
KIT	-0.01	0.25	-10000	0	-1.2	20	20
MAP2K2	0.037	0.069	-10000	0	-0.3	8	8
SHC/Grb2/SOS1	-0.02	0.088	-10000	0	-0.42	20	20
STAT5A	0.014	0.14	-10000	0	-0.63	20	20
GRB2	0.01	0	-10000	0	-10000	0	0
response to radiation	0.009	0.1	-10000	0	-0.46	21	21
SHC/GRAP2	-0.012	0.063	-10000	0	-0.35	16	16
PTPRO	-0.012	0.13	-10000	0	-0.47	26	26
SH2B2	0.011	0.1	-10000	0	-0.45	20	20
DOK1	0.01	0	-10000	0	-10000	0	0
MATK	0	0.11	-10000	0	-0.46	21	21
CREBBP	0.029	0.007	-10000	0	-10000	0	0
BCL2	0.028	0.085	-10000	0	-1.2	1	1

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.01	0	-9999	-10000	0	0
VLDLR	-0.002	0.075	-9999	-0.5	11	11
LRPAP1	0.01	0	-9999	-10000	0	0
NUDC	0.01	0	-9999	-10000	0	0
RELN/LRP8	-0.052	0.11	-9999	-0.29	86	86
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0.01	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.024	0.11	-9999	-0.27	18	18
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	-0.003	0.067	-9999	-0.52	8	8
IQGAP1	0.01	0	-9999	-10000	0	0
PLA2G7	-0.001	0.074	-9999	-0.51	10	10
CALM1	0.01	0	-9999	-10000	0	0
DYNLT1	0.01	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.008	0.054	-9999	-0.37	11	11
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.01	0	-9999	-10000	0	0
CDK5R1	-0.006	0.091	-9999	-0.52	15	15
LIS1/Poliovirus Protein 3A	0	0	-9999	-10000	0	0
CDK5R2	-0.14	0.23	-9999	-0.52	133	133
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.057	0.13	-9999	-0.32	86	86
YWHAE	0.01	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.038	0.11	-9999	-0.33	28	28
MAP1B	-0.002	0.02	-9999	-0.28	1	1
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.017	0.1	-9999	-0.47	1	1
RELN	-0.069	0.18	-9999	-0.5	75	75
PAFAH/LIS1	0.014	0.046	-9999	-0.3	10	10
LIS1/CLIP170	0.021	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.048	0.072	-9999	-0.33	1	1
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.019	0.11	-9999	-0.37	15	15
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.046	0.12	-9999	-0.35	28	28
LIS1/IQGAP1	0.021	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.018	0	-9999	-10000	0	0
PAFAH1B3	-0.015	0.11	-9999	-0.52	23	23
PAFAH1B2	0.01	0	-9999	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0.018	0.014	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.061	0.088	-9999	-0.4	1	1
LRP8	-0.002	0.078	-9999	-0.52	11	11
NDEL1/Katanin 60	-0.038	0.11	-9999	-0.33	28	28
P39/CDK5	-0.082	0.16	-9999	-0.47	28	28
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.021	0	-9999	-10000	0	0
CDK5	-0.015	0.1	-9999	-10000	0	0
PPP2R5D	0.01	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0	-9999	-10000	0	0
CSNK2A1	0.01	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.046	0.1	-9999	-0.49	8	8
RELN/VLDLR	-0.052	0.11	-9999	-0.32	23	23
CDC42	0	0	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.023	0.088	-9999	-0.36	31	31
CRKL	0.006	0.081	-9999	-0.4	7	7
mol:PIP3	-0.016	0.006	-9999	-10000	0	0
AKT1	0.001	0.004	-9999	-10000	0	0
PTK2B	0.008	0.032	-9999	-0.5	2	2
RAPGEF1	0.012	0.078	-9999	-0.4	6	6
RANBP10	0.01	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
HGF/MET/SHIP2	-0.035	0.1	-9999	-0.31	55	55
MAP3K5	0.017	0.08	-9999	-0.4	7	7
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.031	0.089	-9999	-0.28	55	55
AP1	-0.028	0.085	-9999	-0.32	36	36
mol:SU11274	0	0	-9999	-10000	0	0
SHC1	0.009	0.024	-9999	-0.52	1	1
apoptosis	-0.041	0.19	-9999	-0.7	36	36
STAT3 (dimer)	0.008	0.077	-9999	-0.39	4	4
GAB1/CRKL/SHP2/PI3K	-0.019	0.064	-9999	-0.42	5	5
INPP5D	0.007	0.04	-9999	-0.5	3	3
CBL/CRK	0.011	0.078	-9999	-0.4	6	6
PTPN11	0.01	0	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
PLCG1	0.01	0	-9999	-10000	0	0
PTEN	0.01	0	-9999	-10000	0	0
ELK1	-0.011	0.047	-9999	-0.19	31	31
mol:SU5416	0	0	-9999	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.014	0.043	-9999	-0.25	4	4
PAK1	0.007	0.004	-9999	-10000	0	0
HGF/MET/RANBP10	-0.035	0.1	-9999	-0.31	55	55
HRAS	-0.007	0.12	-9999	-0.56	18	18
DOCK1	0.012	0.078	-9999	-0.4	6	6
GAB1	0	0.085	-9999	-0.31	21	21
CRK	0.006	0.081	-9999	-0.29	21	21
mol:PHA665752	0	0	-9999	-10000	0	0
mol:GDP	-0.041	0.13	-9999	-0.49	38	38
JUN	0.006	0.046	-9999	-0.5	4	4
EntrezGene:200958	0	0	-9999	-10000	0	0
HGF/MET	-0.022	0.065	-9999	-0.22	38	38
PIK3R1	0.009	0.023	-9999	-0.5	1	1
cell morphogenesis	0.028	0.085	-9999	-0.43	4	4
GRB2/SHC	0.002	0.062	-9999	-0.3	4	4
FOS	-0.023	0.13	-9999	-0.5	32	32
GLMN	0	0	-9999	-10000	0	0
cell motility	-0.011	0.047	-9999	-0.19	31	31
HGF/MET/MUC20	-0.036	0.1	-9999	-0.32	55	55
cell migration	0.002	0.061	-9999	-0.29	4	4
GRB2	0.01	0	-9999	-10000	0	0
CBL	0.01	0	-9999	-10000	0	0
MET/RANBP10	-0.023	0.088	-9999	-0.36	31	31
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.003	0.079	-9999	-0.41	4	4
MET/MUC20	-0.023	0.089	-9999	-0.37	31	31
RAP1B	0.017	0.074	-9999	-0.43	4	4
RAP1A	0.017	0.074	-9999	-0.43	4	4
HGF/MET/RANBP9	-0.035	0.1	-9999	-0.31	55	55
RAF1	0	0.12	-9999	-0.52	18	18
STAT3	0.008	0.078	-9999	-0.4	4	4
cell proliferation	0.01	0.1	-9999	-0.33	38	38
RPS6KB1	0.002	0.027	-9999	-10000	0	0
MAPK3	-0.014	0.042	-9999	-10000	0	0
MAPK1	-0.014	0.042	-9999	-10000	0	0
RANBP9	0.01	0	-9999	-10000	0	0
MAPK8	0.03	0.068	-9999	-0.38	3	3
SRC	0.009	0.074	-9999	-0.38	4	4
PI3K	0.002	0.064	-9999	-0.34	4	4
MET/Glomulin	-0.011	0.08	-9999	-0.32	31	31
SOS1	0.01	0	-9999	-10000	0	0
MAP2K1	0.007	0.11	-9999	-0.5	16	16
MET	-0.023	0.13	-9999	-0.51	31	31
MAP4K1	0.011	0.085	-9999	-0.4	9	9
PTK2	0.01	0	-9999	-10000	0	0
MAP2K2	0.007	0.11	-9999	-0.5	16	16
BAD	0.007	0.004	-9999	-10000	0	0
MAP2K4	0.022	0.074	-9999	-0.38	6	6
SHP2/GRB2/SOS1/GAB1	-0.024	0.078	-9999	-0.34	20	20
INPPL1	0.01	0	-9999	-10000	0	0
PXN	0.01	0	-9999	-10000	0	0
SH3KBP1	0.01	0	-9999	-10000	0	0
HGS	-0.004	0.064	-9999	-0.24	18	18
PLCgamma1/PKC	0	0	-9999	-10000	0	0
HGF	-0.018	0.12	-9999	-0.5	27	27
RASA1	0.01	0	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
PTPRJ	0.01	0	-9999	-10000	0	0
NCK/PLCgamma1	0.003	0.064	-9999	-0.33	3	3
PDPK1	-0.006	0.005	-9999	-10000	0	0
HGF/MET/SHIP	-0.037	0.11	-9999	-0.32	55	55

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	-0.001	0.017	-10000	0	-0.37	1	1
PRKCZ	0.007	0.04	-10000	0	-0.5	3	3
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.01	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.01	0.039	-10000	0	-0.26	2	2
IRAK/TOLLIP	0.021	0.019	-10000	0	-0.27	2	2
IKBKB	0.01	0	-10000	0	-10000	0	0
IKBKG	0.01	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.12	0.17	-10000	0	-0.36	168	168
IL1A	-0.15	0.24	-10000	0	-0.5	151	151
IL1B	-0.007	0.093	-10000	0	-0.35	33	33
IRAK/TRAF6/p62/Atypical PKCs	-0.003	0.024	-10000	0	-10000	0	0
IL1R2	-0.012	0.1	-10000	0	-0.51	20	20
IL1R1	0.007	0.04	-10000	0	-0.5	3	3
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.023	0.051	0.19	9	-0.38	2	11
TOLLIP	0.01	0	-10000	0	-10000	0	0
TICAM2	0.006	0.046	-10000	0	-0.5	4	4
MAP3K3	0.009	0.023	-10000	0	-0.5	1	1
TAK1/TAB1/TAB2	0	0	-10000	0	-10000	0	0
IKK complex/ELKS	0.049	0.017	-10000	0	-10000	0	0
JUN	0.024	0.053	-10000	0	-0.43	1	1
MAP3K7	0.01	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.017	0.062	-10000	0	-0.46	2	2
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.081	0.12	-10000	0	-0.39	4	4
PIK3R1	0.009	0.023	-10000	0	-0.5	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.074	0.11	-10000	0	-0.49	2	2
IL1 beta fragment/IL1R1/IL1RAP	-0.019	0.071	-10000	0	-0.27	34	34
NFKB1	0.01	0	-10000	0	-10000	0	0
MAPK8	0.021	0.049	-10000	0	-10000	0	0
IRAK1	0.016	0.021	-10000	0	-0.31	2	2
IL1RN/IL1R1	-0.007	0.05	-10000	0	-0.35	10	10
IRAK4	0.01	0	-10000	0	-10000	0	0
PRKCI	0.01	0	-10000	0	-10000	0	0
TRAF6	0.01	0	-10000	0	-10000	0	0
PI3K	-0.001	0.016	-10000	0	-0.35	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.018	0.054	-10000	0	-0.39	2	2
CHUK	0.01	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.019	0.071	-10000	0	-0.27	34	34
IL1 beta/IL1R2	-0.032	0.097	-10000	0	-0.31	50	50
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.001	0.015	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.015	0.055	-10000	0	-0.42	2	2
IRAK3	-0.003	0.079	-10000	0	-0.5	12	12
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.018	0.064	-10000	0	-0.46	2	2
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.049	0.12	-10000	0	-0.46	2	2
IL1 alpha/IL1R1/IL1RAP	-0.092	0.14	-10000	0	-0.29	152	152
RELA	0.01	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.009	0.024	-10000	0	-0.52	1	1
MYD88	0.01	0	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0.014	0.024	-10000	0	-10000	0	0
IL1RAP	0.01	0	-10000	0	-10000	0	0
UBE2N	0.01	0	-10000	0	-10000	0	0
IRAK/TRAF6	-0.015	0.053	-10000	0	-0.38	2	2
CASP1	0.005	0.051	-10000	0	-0.5	5	5
IL1RN/IL1R2	-0.02	0.085	-10000	0	-0.37	26	26
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.017	0.065	-10000	0	-0.49	2	2
TMEM189-UBE2V1	0.003	0.024	-10000	0	-0.52	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.031	0.099	-10000	0	-0.42	3	3
PIK3CA	0.01	0	-10000	0	-10000	0	0
IL1RN	0.003	0.06	-10000	0	-0.5	7	7
TRAF6/TAK1/TAB1/TAB2	0	0.011	-10000	0	-10000	0	0
MAP2K6	0.015	0.051	-10000	0	-10000	0	0

×

S1P1 pathway

Figure S70. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S70. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.009	0.055	-9999	-0.36	12	12
PDGFRB	0.008	0.023	-9999	-0.5	1	1
SPHK1	-0.009	0.021	-9999	-10000	0	0
mol:S1P	-0.011	0.027	-9999	-10000	0	0
S1P1/S1P/Gi	-0.013	0.14	-9999	-0.36	49	49
GNAO1	0.003	0.058	-9999	-0.52	6	6
PDGFB-D/PDGFRB/PLCgamma1	-0.005	0.12	-9999	-0.45	11	11
PLCG1	-0.008	0.13	-9999	-0.34	47	47
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.008	0.023	-9999	-0.5	1	1
GNAI2	0.01	0.004	-9999	-10000	0	0
GNAI3	0.01	0.003	-9999	-10000	0	0
GNAI1	0.008	0.033	-9999	-0.51	2	2
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.005	0.05	-9999	-0.3	12	12
S1P1/S1P	-0.02	0.053	-9999	-0.35	4	4
negative regulation of cAMP metabolic process	-0.012	0.13	-9999	-0.35	49	49
MAPK3	-0.023	0.18	-9999	-0.53	47	47
calcium-dependent phospholipase C activity	-0.001	0.003	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
KDR	-0.003	0.079	-9999	-0.5	12	12
PLCB2	0.01	0.071	-9999	-0.34	7	7
RAC1	0.01	0	-9999	-10000	0	0
RhoA/GTP	-0.017	0.045	-9999	-0.3	4	4
receptor internalization	-0.019	0.05	-9999	-0.3	6	6
PTGS2	-0.063	0.31	-9999	-0.98	47	47
Rac1/GTP	-0.017	0.045	-9999	-0.3	4	4
RHOA	0.01	0	-9999	-10000	0	0
VEGFA	0.009	0.003	-9999	-10000	0	0
negative regulation of T cell proliferation	-0.012	0.13	-9999	-0.35	49	49
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.033	0.14	-9999	-0.5	41	41
MAPK1	-0.023	0.18	-9999	-0.53	47	47
S1P1/S1P/PDGFB-D/PDGFRB	0.011	0.074	-9999	-0.37	4	4
ABCC1	0.01	0.002	-9999	-10000	0	0

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.02	0.085	-10000	0	-0.49	12	12
FYN	0.03	0.13	-10000	0	-0.61	15	15
LAT/GRAP2/SLP76	-0.016	0.11	-10000	0	-0.5	18	18
IKBKB	0.01	0	-10000	0	-10000	0	0
AKT1	0.037	0.095	-10000	0	-0.41	15	15
B2M	0.011	0.003	-10000	0	-10000	0	0
IKBKG	-0.009	0.024	-10000	0	-0.14	6	6
MAP3K8	0.008	0.032	-10000	0	-0.5	2	2
mol:Ca2+	-0.01	0.025	-10000	0	-0.11	13	13
integrin-mediated signaling pathway	-0.001	0.019	-10000	0	-0.3	2	2
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.034	0.14	-10000	0	-0.6	16	16
TRPV6	-0.075	0.18	-10000	0	-0.51	72	72
CD28	0.009	0.023	-10000	0	-0.5	1	1
SHC1	0.029	0.12	-10000	0	-0.57	15	15
receptor internalization	0.022	0.13	-10000	0	-0.53	17	17
PRF1	-0.017	0.26	-10000	0	-1.1	25	25
KRAS	0.009	0.024	-10000	0	-0.52	1	1
GRB2	0.01	0	-10000	0	-10000	0	0
COT/AKT1	0.038	0.08	-10000	0	-0.35	14	14
LAT	0.029	0.12	-10000	0	-0.58	14	14
EntrezGene:6955	0	0.005	-10000	0	-10000	0	0
CD3D	0.008	0.041	-10000	0	-0.51	3	3
CD3E	0.006	0.053	-10000	0	-0.52	5	5
CD3G	-0.001	0.076	-10000	0	-0.5	11	11
RASGRP2	0.002	0.041	-10000	0	-0.16	26	26
RASGRP1	0.035	0.1	-10000	0	-0.4	18	18
HLA-A	0.011	0.003	-10000	0	-10000	0	0
RASSF5	0.008	0.032	-10000	0	-0.5	2	2
RAP1A/GTP/RAPL	-0.001	0.019	-10000	0	-0.3	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.029	0.037	-10000	0	-0.12	11	11
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.015	0.043	-10000	0	-0.23	9	9
PRKCA	-0.005	0.053	-10000	0	-0.26	12	12
GRAP2	-0.006	0.088	-10000	0	-0.5	15	15
mol:IP3	0.01	0.11	0.21	62	-0.42	12	74
EntrezGene:6957	0.001	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	0.014	0.11	-10000	0	-0.57	12	12
ORAI1	0.043	0.1	0.28	72	-10000	0	72
CSK	0.029	0.12	-10000	0	-0.64	12	12
B7 family/CD28	-0.034	0.14	-10000	0	-0.65	18	18
CHUK	0.01	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	0.023	0.14	-10000	0	-0.63	16	16
PTPN6	0.026	0.12	-10000	0	-0.59	14	14
VAV1	0.028	0.13	-10000	0	-0.58	16	16
Monovalent TCR/CD3	0.007	0.088	-10000	0	-0.37	18	18
CBL	0.01	0	-10000	0	-10000	0	0
LCK	0.027	0.13	-10000	0	-0.64	14	14
PAG1	0.028	0.12	-10000	0	-0.64	12	12
RAP1A	0.01	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	0.022	0.14	-10000	0	-0.68	14	14
CD80	-0.001	0.076	-10000	0	-0.5	11	11
CD86	0.001	0.069	-10000	0	-0.5	9	9
PDK1/CARD11/BCL10/MALT1	-0.018	0.052	-10000	0	-0.26	11	11
HRAS	0.01	0	-10000	0	-10000	0	0
GO:0035030	0.024	0.13	-10000	0	-0.55	17	17
CD8A	0.004	0.062	-10000	0	-0.51	7	7
CD8B	0.003	0.066	-10000	0	-0.51	8	8
PTPRC	-0.005	0.089	-10000	0	-0.5	15	15
PDK1/PKC theta	0.032	0.12	-10000	0	-0.47	20	20
CSK/PAG1	0.032	0.12	-10000	0	-0.64	11	11
SOS1	0.01	0	-10000	0	-10000	0	0
peptide-MHC class I	0.016	0.007	-10000	0	-10000	0	0
GRAP2/SLP76	-0.02	0.13	-10000	0	-0.58	18	18
STIM1	0.021	0.05	-10000	0	-10000	0	0
RAS family/GTP	0.038	0.042	-10000	0	-0.18	6	6
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	0.021	0.14	-10000	0	-0.57	17	17
mol:DAG	-0.006	0.077	-10000	0	-0.35	15	15
RAP1A/GDP	0.013	0.016	-10000	0	-10000	0	0
PLCG1	0.01	0	-10000	0	-10000	0	0
CD247	0.004	0.057	-10000	0	-0.5	6	6
cytotoxic T cell degranulation	-0.013	0.24	-10000	0	-1.1	25	25
RAP1A/GTP	-0.004	0.013	-10000	0	-0.066	5	5
mol:PI-3-4-5-P3	0.036	0.11	-10000	0	-0.48	16	16
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.007	0.13	0.23	62	-0.52	14	76
NRAS	0.01	0	-10000	0	-10000	0	0
ZAP70	0.004	0.056	-10000	0	-0.5	6	6
GRB2/SOS1	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.016	0.1	-10000	0	-0.52	15	15
MALT1	0.01	0	-10000	0	-10000	0	0
TRAF6	0.01	0	-10000	0	-10000	0	0
CD8 heterodimer	0.005	0.076	-10000	0	-0.48	11	11
CARD11	-0.022	0.13	-10000	0	-0.52	30	30
PRKCB	-0.008	0.067	-10000	0	-0.3	18	18
PRKCE	-0.006	0.055	-10000	0	-0.27	12	12
PRKCQ	0.024	0.14	-10000	0	-0.52	22	22
LCP2	0.007	0.04	-10000	0	-0.5	3	3
BCL10	0.01	0	-10000	0	-10000	0	0
regulation of survival gene product expression	0.037	0.082	-10000	0	-0.35	15	15
IKK complex	0.037	0.034	-10000	0	-0.11	11	11
RAS family/GDP	-0.002	0.006	-10000	0	-10000	0	0
MAP3K14	0.039	0.062	-10000	0	-0.29	10	10
PDPK1	0.039	0.091	-10000	0	-0.4	14	14
TCR/CD3/MHC I/CD8/Fyn	0.02	0.14	-10000	0	-0.72	12	12

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.016	0.086	-10000	0	-0.41	5	5
IKBKB	-0.002	0.048	-10000	0	-0.25	3	3
AKT1	-0.03	0.08	-10000	0	-0.26	4	4
IKBKG	0	0.05	-10000	0	-0.26	4	4
CALM1	-0.014	0.079	0.23	1	-0.59	5	6
PIK3CA	0.01	0	-10000	0	-10000	0	0
MAP3K1	-0.035	0.11	-10000	0	-0.56	4	4
MAP3K7	0.01	0	-10000	0	-10000	0	0
mol:Ca2+	-0.02	0.084	0.2	5	-0.63	5	10
DOK1	0.01	0	-10000	0	-10000	0	0
AP-1	-0.005	0.058	0.16	3	-0.25	6	9
LYN	0.01	0	-10000	0	-10000	0	0
BLNK	0.008	0.032	-10000	0	-0.5	2	2
SHC1	0.009	0.024	-10000	0	-0.52	1	1
BCR complex	-0.075	0.16	-10000	0	-0.39	93	93
CD22	-0.05	0.11	-10000	0	-0.44	16	16
CAMK2G	-0.007	0.074	0.22	1	-0.54	5	6
CSNK2A1	0.01	0	-10000	0	-10000	0	0
INPP5D	0.007	0.04	-10000	0	-0.5	3	3
SHC/GRB2/SOS1	-0.045	0.098	-10000	0	-0.44	11	11
GO:0007205	-0.021	0.086	0.2	5	-0.65	5	10
SYK	0.007	0.04	-10000	0	-0.5	3	3
ELK1	-0.014	0.081	0.23	1	-0.6	5	6
NFATC1	-0.055	0.12	-10000	0	-0.41	14	14
B-cell antigen/BCR complex	-0.075	0.16	-10000	0	-0.39	93	93
PAG1/CSK	-0.001	0.016	-10000	0	-0.35	1	1
NFKBIB	0.006	0.019	-10000	0	-10000	0	0
HRAS	-0.012	0.079	0.21	1	-0.54	5	6
NFKBIA	0.007	0.019	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.011	0.016	-10000	0	-10000	0	0
RasGAP/Csk	-0.052	0.11	-10000	0	-0.5	9	9
mol:GDP	-0.021	0.083	0.24	1	-0.63	5	6
PTEN	0.01	0	-10000	0	-10000	0	0
CD79B	0	0.071	-10000	0	-0.52	9	9
NF-kappa-B/RelA/I kappa B alpha	0.011	0.016	-10000	0	-10000	0	0
GRB2	0.01	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.065	0.13	-10000	0	-0.43	12	12
PIK3R1	0.009	0.023	-10000	0	-0.5	1	1
mol:IP3	-0.026	0.085	0.2	5	-0.66	5	10
CSK	0.01	0	-10000	0	-10000	0	0
FOS	-0.022	0.096	0.22	1	-0.44	11	12
CHUK	0	0.05	-10000	0	-0.26	4	4
IBTK	0.01	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.033	0.077	-10000	0	-0.42	9	9
PTPN6	-0.046	0.098	-10000	0	-0.54	9	9
RELA	0.01	0	-10000	0	-10000	0	0
BCL2A1	0.01	0.02	-10000	0	-0.089	13	13
VAV2	-0.11	0.15	-10000	0	-0.37	91	91
ubiquitin-dependent protein catabolic process	0.01	0.018	-10000	0	-10000	0	0
BTK	-0.069	0.25	0.32	1	-1	32	33
CD19	-0.13	0.17	-10000	0	-0.42	91	91
MAP4K1	0.005	0.051	-10000	0	-0.5	5	5
CD72	0.008	0.032	-10000	0	-0.5	2	2
PAG1	0.009	0.023	-10000	0	-0.5	1	1
MAPK14	-0.024	0.1	-10000	0	-0.46	4	4
SH3BP5	0.004	0.056	-10000	0	-0.5	6	6
PIK3AP1	-0.015	0.1	0.21	4	-0.55	11	15
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.011	0.11	-10000	0	-0.84	6	6
RAF1	-0.006	0.075	0.21	1	-0.5	5	6
RasGAP/p62DOK/SHIP	-0.05	0.11	-10000	0	-0.48	10	10
CD79A	-0.089	0.21	-10000	0	-0.52	92	92
re-entry into mitotic cell cycle	-0.005	0.058	0.16	3	-0.25	6	9
RASA1	0.01	0	-10000	0	-10000	0	0
MAPK3	0.007	0.064	0.2	1	-0.4	5	6
MAPK1	0.007	0.064	-10000	0	-0.4	5	5
CD72/SHP1	-0.015	0.11	-10000	0	-0.52	9	9
NFKB1	0.01	0	-10000	0	-10000	0	0
MAPK8	-0.024	0.1	-10000	0	-0.46	4	4
actin cytoskeleton organization	-0.074	0.15	-10000	0	-0.32	91	91
NF-kappa-B/RelA	0.026	0.029	0.14	1	-10000	0	1
Calcineurin	-0.02	0.058	-10000	0	-0.48	5	5
PI3K	-0.097	0.12	-10000	0	-0.44	12	12
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.026	0.084	0.22	4	-0.67	5	9
SOS1	0.01	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.009	0.1	-10000	0	-0.69	6	6
DAPP1	-0.028	0.094	-10000	0	-0.85	4	4
cytokine secretion	-0.051	0.12	-10000	0	-0.38	14	14
mol:DAG	-0.026	0.085	0.2	5	-0.66	5	10
PLCG2	0.007	0.04	-10000	0	-0.5	3	3
MAP2K1	0.001	0.07	0.2	1	-0.46	5	6
B-cell antigen/BCR complex/FcgammaRIIB	-0.063	0.14	-10000	0	-0.33	93	93
mol:PI-3-4-5-P3	-0.074	0.091	-10000	0	-0.31	12	12
ETS1	-0.001	0.07	0.22	1	-0.46	6	7
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.054	0.12	-10000	0	-0.5	11	11
B-cell antigen/BCR complex/LYN	-0.039	0.091	-10000	0	-0.43	10	10
MALT1	0.01	0	-10000	0	-10000	0	0
TRAF6	0.01	0	-10000	0	-10000	0	0
RAC1	-0.078	0.16	-10000	0	-0.34	88	88
B-cell antigen/BCR complex/LYN/SYK	-0.054	0.11	-10000	0	-0.42	17	17
CARD11	-0.03	0.1	0.23	1	-0.31	34	35
FCGR2B	0.009	0.023	-10000	0	-0.5	1	1
PPP3CA	0.01	0	-10000	0	-10000	0	0
BCL10	0.01	0	-10000	0	-10000	0	0
IKK complex	0.004	0.025	-10000	0	-0.092	2	2
PTPRC	-0.006	0.088	-10000	0	-0.5	15	15
PDPK1	-0.032	0.079	-10000	0	-0.25	4	4
PPP3CB	0.01	0	-10000	0	-10000	0	0
PPP3CC	0.01	0	-10000	0	-10000	0	0
POU2F2	0.012	0.012	-10000	0	-0.1	1	1

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	-0.18	0.25	-10000	0	-0.52	178	178
mol:Halofuginone	0.004	0	-10000	0	-10000	0	0
ITGA1	0.006	0.046	-10000	0	-0.5	4	4
CDKN1A	0.017	0.042	-10000	0	-0.61	1	1
PRL-3/alpha Tubulin	-0.001	0.017	-10000	0	-0.37	1	1
mol:Ca2+	-0.064	0.14	0.2	1	-0.38	83	84
AGT	-0.079	0.2	-10000	0	-0.52	83	83
CCNA2	-0.051	0.14	-10000	0	-0.49	15	15
TUBA1B	0.01	0	-10000	0	-10000	0	0
EGR1	-0.004	0.09	-10000	0	-0.35	31	31
CDK2/Cyclin E1	-0.072	0.14	-10000	0	-0.37	20	20
MAPK3	0.017	0.017	-10000	0	-0.37	1	1
PRL-2 /Rab GGTase beta	0	0	-10000	0	-10000	0	0
MAPK1	0.017	0.017	-10000	0	-0.37	1	1
PTP4A1	0.012	0.068	-10000	0	-10000	0	0
PTP4A3	0.009	0.024	-10000	0	-0.52	1	1
PTP4A2	0.01	0	-10000	0	-10000	0	0
ITGB1	0.017	0.017	-10000	0	-0.37	1	1
SRC	0.01	0	-10000	0	-10000	0	0
RAC1	0.018	0.032	-10000	0	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0	0	-10000	0	-10000	0	0
PRL-1/ATF-5	0.015	0.065	-10000	0	-10000	0	0
RABGGTA	0.01	0	-10000	0	-10000	0	0
BCAR1	0	0.019	0.2	1	-0.36	1	2
RHOC	0.018	0.032	-10000	0	-10000	0	0
RHOA	0.018	0.032	-10000	0	-10000	0	0
cell motility	0.021	0.035	-10000	0	-10000	0	0
PRL-1/alpha Tubulin	0.016	0.063	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	-0.004	0.036	-10000	0	-0.36	5	5
ROCK1	0.021	0.035	-10000	0	-10000	0	0
RABGGTB	0.01	0	-10000	0	-10000	0	0
CDK2	0.01	0	-10000	0	-10000	0	0
mitosis	0.012	0.068	-10000	0	-10000	0	0
ATF5	0.009	0.024	-10000	0	-0.52	1	1

×

BARD1 signaling events

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
BARD1/CSTF1	-0.002	0.028	-10000	0	-0.36	3	3
ATM	0.01	0	-10000	0	-10000	0	0
UBE2D3	0.01	0	-10000	0	-10000	0	0
PRKDC	0.01	0	-10000	0	-10000	0	0
ATR	0.01	0	-10000	0	-10000	0	0
UBE2L3	0.01	0	-10000	0	-10000	0	0
FANCD2	0.02	0.013	-10000	0	-10000	0	0
protein ubiquitination	-0.092	0.12	-10000	0	-0.5	4	4
XRCC5	0.01	0	-10000	0	-10000	0	0
XRCC6	0.01	0	-10000	0	-10000	0	0
M/R/N Complex	0	0	-10000	0	-10000	0	0
MRE11A	0.01	0	-10000	0	-10000	0	0
DNA-PK	0	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	-0.006	0.02	-10000	0	-10000	0	0
FANCF	0.01	0	-10000	0	-10000	0	0
BRCA1	0.007	0.041	-10000	0	-0.52	3	3
CCNE1	-0.18	0.25	-10000	0	-0.52	178	178
CDK2/Cyclin E1	-0.13	0.18	-10000	0	-0.37	178	178
FANCG	0.01	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	-0.004	0.04	-10000	0	-0.36	6	6
FANCE	0.01	0	-10000	0	-10000	0	0
FANCC	0.01	0	-10000	0	-10000	0	0
NBN	0.01	0	-10000	0	-10000	0	0
FANCA	-0.01	0.099	-10000	0	-0.52	18	18
DNA repair	-0.017	0.12	-10000	0	-0.4	13	13
BRCA1/BARD1/ubiquitin	-0.004	0.04	-10000	0	-0.36	6	6
BARD1/DNA-PK	-0.002	0.02	-10000	0	-0.27	1	1
FANCL	0.01	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.002	0.028	0.36	3	-10000	0	3
BRCA1/BARD1/CTIP/M/R/N Complex	0.03	0.019	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1/TopBP1	-0.004	0.033	-10000	0	-0.3	6	6
BRCA1/BARD1/P53	-0.003	0.029	-10000	0	-0.26	6	6
BARD1/CSTF1/BRCA1	-0.004	0.033	-10000	0	-0.3	6	6
BRCA1/BACH1	0.007	0.041	-10000	0	-0.52	3	3
BARD1	0.007	0.04	-10000	0	-0.5	3	3
PCNA	0.008	0.034	-10000	0	-0.52	2	2
BRCA1/BARD1/UbcH5C	-0.004	0.033	-10000	0	-0.3	6	6
BRCA1/BARD1/UbcH7	-0.004	0.033	-10000	0	-0.3	6	6
BRCA1/BARD1/RAD51/PCNA	-0.052	0.11	-10000	0	-0.28	87	87
BARD1/DNA-PK/P53	-0.001	0.019	-10000	0	-10000	0	0
BRCA1/BARD1/Ubiquitin	-0.004	0.04	-10000	0	-0.36	6	6
BRCA1/BARD1/CTIP	-0.003	0.029	-10000	0	-0.27	4	4
FA complex	0.026	0.029	-10000	0	-10000	0	0
BARD1/EWS	-0.002	0.028	-10000	0	-0.36	3	3
RBBP8	0.018	0	-10000	0	-10000	0	0
TP53	0.01	0	-10000	0	-10000	0	0
TOPBP1	0.01	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.003	0.029	0.26	6	-10000	0	6
BRCA1/BARD1	-0.093	0.12	-10000	0	-0.51	4	4
CSTF1	0.01	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.002	0.028	-10000	0	-0.36	3	3
CDK2	0.01	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.083	0.2	-10000	0	-0.52	86	86
RAD50	0.01	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.004	0.04	-10000	0	-0.36	6	6
EWSR1	0.01	0	-10000	0	-10000	0	0

×

Ephrin A 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.01	0.058	-9999	-0.33	15	15
EFNA5	0.002	0.062	-9999	-0.51	7	7
FYN	0.008	0.056	-9999	-0.29	16	16
neuron projection morphogenesis	-0.01	0.058	-9999	-0.33	15	15
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.01	0.058	-9999	-0.33	15	15
EPHA5	-0.003	0.071	-9999	-0.52	9	9

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.03	0.073	0.4	5	-10000	0	5
GNAI2	0.01	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.021	0.076	-10000	0	-0.3	34	34
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.004	0.057	-10000	0	-0.51	6	6
RhoA/GTP	-0.03	0.075	-10000	0	-0.41	5	5
negative regulation of cAMP metabolic process	-0.011	0.093	-10000	0	-0.25	36	36
GNAZ	-0.033	0.14	-10000	0	-0.5	41	41
GNAI3	0.01	0	-10000	0	-10000	0	0
GNA12	0.01	0	-10000	0	-10000	0	0
S1PR5	-0.026	0.13	-10000	0	-0.5	34	34
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.011	0.094	-10000	0	-0.25	36	36
RhoA/GDP	0	0	-10000	0	-10000	0	0
RHOA	0.01	0	-10000	0	-10000	0	0
GNAI1	0.008	0.032	-10000	0	-0.5	2	2

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	0.004	0.057	-9999	-0.51	6	6
CDC42/GTP	-0.027	0.069	-9999	-0.4	4	4
PLCG1	0	0.083	-9999	-0.41	4	4
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.01	0	-9999	-10000	0	0
GNAI3	0.01	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
cell migration	-0.027	0.068	-9999	-0.39	4	4
S1PR5	-0.026	0.13	-9999	-0.5	34	34
S1PR4	-0.017	0.11	-9999	-0.5	26	26
MAPK3	0	0.083	-9999	-0.41	4	4
MAPK1	0	0.083	-9999	-0.41	4	4
S1P/S1P5/Gi	-0.011	0.094	-9999	-0.25	36	36
GNAI1	0.008	0.032	-9999	-0.5	2	2
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.021	0.076	-9999	-0.3	34	34
RHOA	0.011	0.059	-9999	-0.24	26	26
S1P/S1P4/Gi	-0.007	0.088	-9999	-0.25	29	29
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.033	0.14	-9999	-0.5	41	41
S1P/S1P4/G12/G13	-0.014	0.059	-9999	-0.26	26	26
GNA12	0.01	0	-9999	-10000	0	0
GNA13	0.01	0	-9999	-10000	0	0
CDC42	0.01	0	-9999	-10000	0	0

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.009	0.039	-9999	-0.32	4	4
NFATC2	-0.001	0.068	-9999	-0.31	20	20
NFATC3	0.012	0.025	-9999	-10000	0	0
CD40LG	-0.031	0.22	-9999	-0.71	23	23
PTGS2	-0.047	0.24	-9999	-0.66	34	34
JUNB	0.007	0.04	-9999	-0.5	3	3
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.005	0.009	-9999	-10000	0	0
CaM/Ca2+	-0.005	0.009	-9999	-10000	0	0
CALM1	0.009	0.007	-9999	-10000	0	0
JUN	0.005	0.046	-9999	-0.5	4	4
mol:Ca2+	-0.005	0.01	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0.002	-9999	-10000	0	0
FOSL1	-0.015	0.11	-9999	-0.52	23	23
CREM	0.01	0	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.048	0.095	-9999	-0.48	11	11
FOS	-0.024	0.13	-9999	-0.51	32	32
IFNG	-0.04	0.23	-9999	-0.65	37	37
AP-1/NFAT1-c-4	-0.073	0.21	-9999	-0.7	25	25
FASLG	-0.024	0.2	-9999	-0.66	21	21
NFAT1-c-4/ICER1	-0.031	0.069	-9999	-0.4	9	9
IL2RA	-0.037	0.22	-9999	-0.62	33	33
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	-0.041	0.23	-9999	-0.69	29	29
JunB/Fra1/NFAT1-c-4	-0.04	0.086	-9999	-0.43	10	10
IL4	-0.026	0.2	-9999	-0.62	20	20
IL2	-0.002	0.01	-9999	-10000	0	0
IL3	-0.01	0.016	-9999	-10000	0	0
FKBP1A	0.01	0	-9999	-10000	0	0
BATF3	0.009	0.024	-9999	-0.52	1	1
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.01	0.001	-9999	-10000	0	0

×

ErbB2/ErbB3 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
USP8	0.015	0.005	-9999	-10000	0	0
RAS family/GTP	-0.04	0.077	-9999	-0.34	1	1
NFATC4	-0.007	0.087	-9999	-0.35	2	2
ERBB2IP	0.01	0.002	-9999	-10000	0	0
HSP90 (dimer)	0.01	0	-9999	-10000	0	0
mammary gland morphogenesis	-0.048	0.091	-9999	-0.42	1	1
JUN	0.019	0.064	-9999	-0.21	4	4
HRAS	0.01	0.001	-9999	-10000	0	0
DOCK7	-0.017	0.1	-9999	-0.4	1	1
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.054	0.1	-9999	-0.51	2	2
AKT1	0.008	0.003	-9999	-10000	0	0
BAD	0.015	0.002	-9999	-10000	0	0
MAPK10	-0.04	0.071	-9999	-0.26	23	23
mol:GTP	0	0.001	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.025	0.11	-9999	-0.46	1	1
RAF1	0.002	0.095	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 2	-0.033	0.089	-9999	-0.27	60	60
STAT3	0.001	0.002	-9999	-10000	0	0
cell migration	-0.003	0.079	-9999	-0.22	23	23
mol:PI-3-4-5-P3	-0.001	0.002	-9999	-10000	0	0
cell proliferation	-0.007	0.17	-9999	-0.53	23	23
FOS	-0.006	0.16	-9999	-0.44	44	44
NRAS	0.01	0.001	-9999	-10000	0	0
mol:Ca2+	-0.048	0.091	-9999	-0.42	1	1
MAPK3	-0.001	0.14	-9999	-0.49	12	12
MAPK1	-0.001	0.14	-9999	-0.49	12	12
JAK2	-0.018	0.1	-9999	-0.41	2	2
NF2	-0.002	0.004	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.032	0.11	-9999	-0.24	102	102
NRG1	-0.095	0.21	-9999	-0.5	101	101
GRB2/SOS1	0	0	-9999	-10000	0	0
MAPK8	-0.019	0.11	-9999	-0.34	1	1
MAPK9	-0.023	0.045	-9999	-0.2	1	1
ERBB2	-0.002	0.03	-9999	-0.38	3	3
ERBB3	0.006	0.033	-9999	-0.5	2	2
SHC1	0.009	0.024	-9999	-0.52	1	1
RAC1	0.01	0	-9999	-10000	0	0
apoptosis	0	0.007	-9999	-10000	0	0
STAT3 (dimer)	0.002	0.004	-9999	-10000	0	0
RNF41	0.019	0.007	-9999	-10000	0	0
FRAP1	0.007	0.002	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.032	0.062	-9999	-0.28	1	1
ErbB2/ErbB2/HSP90 (dimer)	-0.002	0.025	-9999	-0.31	3	3
CHRNA1	-0.001	0.14	-9999	-0.46	22	22
myelination	-0.005	0.087	-9999	-0.33	2	2
PPP3CB	-0.016	0.096	-9999	-0.37	1	1
KRAS	0.009	0.024	-9999	-0.52	1	1
RAC1-CDC42/GDP	-0.039	0.084	-9999	-0.32	2	2
NRG2	-0.048	0.16	-9999	-0.5	55	55
mol:GDP	-0.032	0.11	-9999	-0.24	102	102
SOS1	0.01	0.001	-9999	-10000	0	0
MAP2K2	0.009	0.094	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
mol:cAMP	-0.001	0.001	-9999	-10000	0	0
PTPN11	-0.018	0.1	-9999	-0.4	1	1
MAP2K1	-0.014	0.14	-9999	-0.48	11	11
heart morphogenesis	-0.048	0.091	-9999	-0.42	1	1
RAS family/GDP	-0.04	0.078	-9999	-0.35	1	1
GRB2	0.01	0.001	-9999	-10000	0	0
PRKACA	-0.004	0.007	-9999	-10000	0	0
CHRNE	0.012	0.022	-9999	-0.16	4	4
HSP90AA1	0.01	0	-9999	-10000	0	0
activation of caspase activity	-0.008	0.003	-9999	-10000	0	0
nervous system development	-0.048	0.091	-9999	-0.42	1	1
CDC42	0.01	0	-9999	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	-0.001	0.013	-9999	-0.3	1	1
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.01	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.011	0.1	-9999	-0.52	19	19
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.01	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.005	0.043	-9999	-0.2	4	4
response to UV	0	0	-9999	-10000	0	0
YES1	0.01	0	-9999	-10000	0	0
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.009	0.023	-9999	-0.5	1	1
FYN	0.009	0.023	-9999	-0.5	1	1
MAP3K12	0.01	0	-9999	-10000	0	0
FGR	-0.029	0.14	-9999	-0.5	37	37
p38 alpha/TAB1	-0.016	0.051	-9999	-0.28	10	10
PRKG1	-0.047	0.16	-9999	-0.5	55	55
DUSP8	-0.002	0.075	-9999	-0.5	11	11
PGK/cGMP/p38 alpha	-0.036	0.094	-9999	-0.37	24	24
apoptosis	-0.015	0.049	-9999	-0.33	6	6
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0.01	0	-9999	-10000	0	0
DUSP1	-0.042	0.15	-9999	-0.5	50	50
PAK1	0.01	0	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.001	0.012	-9999	-0.26	1	1
TRAF6	0.01	0	-9999	-10000	0	0
RAC1	0.01	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0.01	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.008	0.094	-9999	-0.37	18	18
BLK	-0.075	0.19	-9999	-0.52	79	79
HCK	-0.012	0.1	-9999	-0.5	21	21
MAP2K3	0.01	0	-9999	-10000	0	0
DUSP16	0.01	0	-9999	-10000	0	0
DUSP10	0.008	0.032	-9999	-0.5	2	2
TRAF6/MEKK3	-0.001	0.012	-9999	-0.27	1	1
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.016	0.068	-9999	-0.37	6	6
positive regulation of innate immune response	0.013	0.099	-9999	-0.39	17	17
LCK	0.007	0.04	-9999	-0.5	3	3
p38alpha-beta/MKP7	0.018	0.095	-9999	-0.42	11	11
p38alpha-beta/MKP5	0.017	0.099	-9999	-0.44	12	12
PGK/cGMP	-0.04	0.11	-9999	-0.36	55	55
PAK2	0.01	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.004	0.12	-9999	-0.45	16	16
CDC42	0.01	0	-9999	-10000	0	0
RALB	0.01	0	-9999	-10000	0	0
RALA	0.01	0	-9999	-10000	0	0
PAK3	-0.058	0.18	-9999	-0.52	62	62

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.006	0.046	-9999	-0.5	4	4
ELF1	0	0.059	-9999	-0.32	1	1
CCNA2	-0.12	0.23	-9999	-0.52	119	119
PIK3CA	0.011	0	-9999	-10000	0	0
JAK3	0.011	0	-9999	-10000	0	0
PIK3R1	0.009	0.023	-9999	-0.5	1	1
JAK1	0.011	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.051	0.047	-9999	-0.5	1	1
SHC1	0.009	0.024	-9999	-0.52	1	1
SP1	0.01	0.046	-9999	-0.32	9	9
IL2RA	-0.005	0.11	-9999	-0.4	35	35
IL2RB	0.008	0.033	-9999	-0.5	2	2
SOS1	0.011	0	-9999	-10000	0	0
IL2RG	0.005	0.051	-9999	-0.5	5	5
G1/S transition of mitotic cell cycle	-0.017	0.13	-9999	-0.72	10	10
PTPN11	0.011	0	-9999	-10000	0	0
CCND2	0.01	0.1	-9999	-0.73	9	9
LCK	0.007	0.04	-9999	-0.5	3	3
GRB2	0.011	0	-9999	-10000	0	0
IL2	0.007	0.005	-9999	-10000	0	0
CDK6	0.007	0.04	-9999	-0.5	3	3
CCND3	0.055	0.043	-9999	-10000	0	0

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.013	0.008	-10000	0	-10000	0	0
HSPA8	0.009	0.004	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.012	0.078	0.2	1	-0.32	24	25
AKT1	0.007	0.02	-10000	0	-10000	0	0
GSC	-0.026	0.1	-10000	0	-0.43	1	1
NKX2-5	-0.028	0.13	-10000	0	-0.51	31	31
muscle cell differentiation	0.021	0.054	0.33	2	-10000	0	2
SMAD2-3/SMAD4/SP1	0.044	0.056	-10000	0	-10000	0	0
SMAD4	0.018	0.024	-10000	0	-10000	0	0
CBFB	0.01	0	-10000	0	-10000	0	0
SAP18	0.01	0.001	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.012	0.078	-10000	0	-0.29	34	34
SMAD3/SMAD4/VDR	0.01	0.032	-10000	0	-0.31	1	1
MYC	0.011	0.038	-10000	0	-0.5	2	2
CDKN2B	-0.062	0.34	-10000	0	-1.3	35	35
AP1	0.027	0.084	-10000	0	-0.49	4	4
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.045	0.022	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.011	0.095	-10000	0	-0.32	23	23
SP3	0.012	0	-10000	0	-10000	0	0
CREB1	0.01	0	-10000	0	-10000	0	0
FOXH1	-0.057	0.17	-10000	0	-0.52	61	61
SMAD3/SMAD4/GR	0.002	0.022	-10000	0	-10000	0	0
GATA3	0.009	0.044	-10000	0	-0.5	3	3
SKI/SIN3/HDAC complex/NCoR1	0.032	0.015	-10000	0	-10000	0	0
MEF2C/TIF2	-0.036	0.1	-10000	0	-0.46	7	7
endothelial cell migration	-0.005	0.068	1.3	1	-10000	0	1
MAX	0.009	0.003	-10000	0	-10000	0	0
RBBP7	0.01	0.001	-10000	0	-10000	0	0
RBBP4	0.01	0.001	-10000	0	-10000	0	0
RUNX2	0.002	0.063	-10000	0	-0.52	7	7
RUNX3	0.007	0.04	-10000	0	-0.5	3	3
RUNX1	0.01	0	-10000	0	-10000	0	0
CTBP1	0.01	0	-10000	0	-10000	0	0
NR3C1	0.009	0.003	-10000	0	-10000	0	0
VDR	0.008	0.033	-10000	0	-0.51	2	2
CDKN1A	0.049	0.068	-10000	0	-1.2	1	1
KAT2B	0.011	0.002	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	-0.043	0.1	-10000	0	-0.31	60	60
DCP1A	0.01	0	-10000	0	-10000	0	0
SKI	0.01	0.001	-10000	0	-10000	0	0
SERPINE1	0.005	0.069	-10000	0	-1.3	1	1
SMAD3/SMAD4/ATF2	0.003	0.022	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	-0.013	0.069	-10000	0	-0.3	23	23
SAP30	0.01	0.001	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.012	0.027	-10000	0	-10000	0	0
JUN	0.027	0.083	-10000	0	-0.49	4	4
SMAD3/SMAD4/IRF7	0.001	0.037	-10000	0	-0.43	2	2
TFE3	0.015	0.003	-10000	0	-10000	0	0
COL1A2	-0.01	0.093	-10000	0	-0.41	20	20
mesenchymal cell differentiation	0.002	0.044	0.32	7	-10000	0	7
DLX1	-0.026	0.13	-10000	0	-0.52	31	31
TCF3	0.01	0	-10000	0	-10000	0	0
FOS	-0.019	0.13	-10000	0	-0.5	32	32
SMAD3/SMAD4/Max	0.002	0.022	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.006	0.013	-10000	0	-10000	0	0
ZBTB17	0.012	0.015	-10000	0	-10000	0	0
LAMC1	0.044	0.026	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.003	0.022	-10000	0	-10000	0	0
IRF7	0.008	0.038	-10000	0	-0.58	2	2
ESR1	-0.017	0.11	-10000	0	-0.51	25	25
HNF4A	-0.11	0.22	-10000	0	-0.52	107	107
MEF2C	-0.016	0.12	-10000	0	-0.46	6	6
SMAD2-3/SMAD4	-0.006	0.027	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.008	0.019	-10000	0	-10000	0	0
IGHV3OR16-13	-0.001	0.006	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.01	0	-10000	0	-10000	0	0
CREBBP	0.012	0.005	-10000	0	-10000	0	0
SKIL	0.01	0	-10000	0	-10000	0	0
HDAC1	0.01	0.001	-10000	0	-10000	0	0
HDAC2	0.01	0.001	-10000	0	-10000	0	0
SNIP1	0.009	0.003	-10000	0	-10000	0	0
GCN5L2	0.002	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.005	0.025	-10000	0	-10000	0	0
MSG1/HSC70	-0.025	0.091	-10000	0	-0.36	34	34
SMAD2	0.007	0.022	-10000	0	-10000	0	0
SMAD3	0.019	0.022	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.036	0.026	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.016	0.012	-10000	0	-10000	0	0
NCOR1	0.01	0.001	-10000	0	-10000	0	0
NCOA2	0.006	0.046	-10000	0	-0.5	4	4
NCOA1	0.01	0	-10000	0	-10000	0	0
MYOD/E2A	-0.002	0.029	-10000	0	-0.37	3	3
SMAD2-3/SMAD4/SP1/MIZ-1	0.049	0.055	-10000	0	-10000	0	0
IFNB1	0.032	0.049	-10000	0	-0.58	2	2
SMAD3/SMAD4/MEF2C	-0.003	0.12	-10000	0	-0.47	5	5
CITED1	-0.027	0.13	-10000	0	-0.5	34	34
SMAD2-3/SMAD4/ARC105	-0.003	0.023	-10000	0	-10000	0	0
RBL1	0.01	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.017	0.13	-10000	0	-0.46	35	35
RUNX1-3/PEBPB2	-0.002	0.023	-10000	0	-0.29	3	3
SMAD7	0.051	0.091	-10000	0	-0.57	3	3
MYC/MIZ-1	0.009	0.045	-10000	0	-0.36	2	2
SMAD3/SMAD4	0.025	0.065	0.28	2	-0.44	1	3
IL10	0.033	0.078	-10000	0	-0.49	9	9
PIASy/HDAC complex	0.008	0.004	-10000	0	-10000	0	0
PIAS3	0.011	0.003	-10000	0	-10000	0	0
CDK2	0.012	0.005	-10000	0	-10000	0	0
IL5	0.033	0.045	-10000	0	-10000	0	0
CDK4	0.008	0.048	-10000	0	-0.52	4	4
PIAS4	0.008	0.005	-10000	0	-10000	0	0
ATF3	-0.015	0.11	-10000	0	-0.5	24	24
SMAD3/SMAD4/SP1	0.003	0.037	-10000	0	-10000	0	0
FOXG1	-0.054	0.16	-10000	0	-0.52	53	53
FOXO3	0.015	0.026	-10000	0	-10000	0	0
FOXO1	0.015	0.026	-10000	0	-10000	0	0
FOXO4	0.015	0.026	-10000	0	-10000	0	0
heart looping	-0.016	0.12	-10000	0	-0.46	6	6
CEBPB	0.009	0.01	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.019	0.083	-10000	0	-0.33	31	31
MYOD1	-0.002	0.041	-10000	0	-0.52	3	3
SMAD3/SMAD4/HNF4	-0.067	0.13	-10000	0	-0.31	107	107
SMAD3/SMAD4/GATA3	-0.001	0.044	-10000	0	-0.35	1	1
SnoN/SIN3/HDAC complex/NCoR1	0.01	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.003	0.032	-10000	0	-0.31	3	3
SMAD3/SMAD4/SP1-3	0.023	0.042	-10000	0	-10000	0	0
MED15	0.01	0	-10000	0	-10000	0	0
SP1	0.013	0.022	-10000	0	-10000	0	0
SIN3B	0.01	0.001	-10000	0	-10000	0	0
SIN3A	0.01	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.035	0.13	-10000	0	-0.38	23	23
ITGB5	0.05	0.035	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.037	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.037	0.11	-10000	0	-0.31	63	63
AR	-0.057	0.17	-10000	0	-0.5	64	64
negative regulation of cell growth	0.035	0.045	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	-0.001	0.033	-10000	0	-0.32	3	3
E2F5	0.006	0.048	-10000	0	-0.52	4	4
E2F4	0.01	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.031	0.083	-10000	0	-0.33	6	6
SMAD2-3/SMAD4/FOXO1-3a-4	0.024	0.095	-10000	0	-0.31	35	35
TFDP1	0.009	0.024	-10000	0	-0.52	1	1
SMAD3/SMAD4/AP1	0.03	0.085	-10000	0	-0.5	4	4
SMAD3/SMAD4/RUNX2	-0.002	0.045	-10000	0	-0.32	7	7
TGIF2	0.01	0	-10000	0	-10000	0	0
TGIF1	0.01	0	-10000	0	-10000	0	0
ATF2	0.01	0	-10000	0	-10000	0	0

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.015	0.061	-10000	0	-0.26	27	27
ER alpha/Gai/GDP/Gbeta gamma	0.005	0.09	-10000	0	-0.37	14	14
AKT1	0.008	0.12	-10000	0	-0.72	12	12
PIK3CA	0.01	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	0.005	0.12	-10000	0	-0.73	12	12
mol:Ca2+	0.014	0.089	-10000	0	-0.41	15	15
IGF1R	0.008	0.032	-10000	0	-0.5	2	2
E2/ER alpha (dimer)/Striatin	-0.016	0.068	-10000	0	-0.3	26	26
SHC1	0.009	0.024	-10000	0	-0.52	1	1
apoptosis	-0.008	0.11	0.69	12	-10000	0	12
RhoA/GTP	-0.011	0.047	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.025	0.074	-10000	0	-0.38	14	14
regulation of stress fiber formation	-0.029	0.051	0.36	1	-10000	0	1
E2/ERA-ERB (dimer)	-0.017	0.07	-10000	0	-0.3	27	27
KRAS	0.009	0.024	-10000	0	-0.52	1	1
G13/GTP	-0.014	0.061	-10000	0	-0.28	25	25
pseudopodium formation	0.029	0.051	-10000	0	-0.36	1	1
E2/ER alpha (dimer)/PELP1	-0.016	0.067	-10000	0	-0.3	25	25
GRB2	0.01	0	-10000	0	-10000	0	0
GNG2	0.008	0.032	-10000	0	-0.5	2	2
GNAO1	0.004	0.057	-10000	0	-0.51	6	6
HRAS	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.012	0.091	-10000	0	-0.43	14	14
E2/ER beta (dimer)	-0.002	0.023	-10000	0	-0.37	2	2
mol:GDP	-0.014	0.061	-10000	0	-0.34	13	13
mol:NADP	0.012	0.091	-10000	0	-0.43	14	14
PIK3R1	0.009	0.023	-10000	0	-0.5	1	1
mol:IP3	0.014	0.093	-10000	0	-0.43	15	15
IGF-1R heterotetramer	0.008	0.032	-10000	0	-0.5	2	2
PLCB1	0.013	0.083	-10000	0	-0.42	14	14
PLCB2	0.008	0.095	-10000	0	-0.45	15	15
IGF1	-0.002	0.076	-10000	0	-0.5	11	11
mol:L-citrulline	0.012	0.091	-10000	0	-0.43	14	14
RHOA	0.01	0	-10000	0	-10000	0	0
Gai/GDP	-0.021	0.074	-10000	0	-0.65	3	3
JNK cascade	-0.002	0.023	-10000	0	-0.37	2	2
BCAR1	0.009	0.023	-10000	0	-0.5	1	1
ESR2	0.008	0.033	-10000	0	-0.51	2	2
GNAQ	0.009	0.023	-10000	0	-0.5	1	1
ESR1	-0.017	0.11	-10000	0	-0.51	25	25
Gq family/GDP/Gbeta gamma	0.023	0.055	-10000	0	-0.43	3	3
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.019	0.047	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.025	0.073	-10000	0	-0.39	13	13
GNAZ	-0.033	0.14	-10000	0	-0.5	41	41
E2/ER alpha (dimer)	-0.019	0.081	-10000	0	-0.37	25	25
STRN	0.009	0.023	-10000	0	-0.5	1	1
GNAL	-0.002	0.076	-10000	0	-0.5	11	11
PELP1	0.01	0	-10000	0	-10000	0	0
MAPK11	0.012	0.032	-10000	0	-0.3	5	5
GNAI2	0.01	0	-10000	0	-10000	0	0
GNAI3	0.01	0	-10000	0	-10000	0	0
GNAI1	0.008	0.032	-10000	0	-0.5	2	2
HBEGF	-0.031	0.11	-10000	0	-0.39	19	19
cAMP biosynthetic process	-0.019	0.067	-10000	0	-0.25	36	36
SRC	0.011	0.086	-10000	0	-0.36	13	13
PI3K	-0.001	0.016	-10000	0	-0.35	1	1
GNB1	0.01	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.013	0.056	-10000	0	-0.32	12	12
SOS1	0.01	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.024	0.07	-10000	0	-0.45	5	5
Gs family/GTP	-0.019	0.068	-10000	0	-0.26	36	36
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.001	0.012	-10000	0	-0.28	1	1
vasodilation	0.013	0.088	-10000	0	-0.41	14	14
mol:DAG	0.014	0.093	-10000	0	-0.43	15	15
Gs family/GDP/Gbeta gamma	-0.016	0.062	-10000	0	-0.34	12	12
MSN	0.03	0.054	-10000	0	-0.39	1	1
Gq family/GTP	-0.018	0.08	-10000	0	-0.45	14	14
mol:PI-3-4-5-P3	0.005	0.12	-10000	0	-0.7	12	12
NRAS	0.01	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.013	0.088	0.41	14	-10000	0	14
GRB2/SOS1	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.013	0.057	-10000	0	-0.32	13	13
NOS3	0.012	0.095	-10000	0	-0.45	14	14
GNA11	0.008	0.032	-10000	0	-0.5	2	2
MAPKKK cascade	0.02	0.097	-10000	0	-0.53	12	12
E2/ER alpha (dimer)/PELP1/Src	-0.026	0.077	-10000	0	-0.41	13	13
ruffle organization	0.029	0.051	-10000	0	-0.36	1	1
ROCK2	0.026	0.053	-10000	0	-10000	0	0
GNA14	-0.005	0.085	-10000	0	-0.5	14	14
GNA15	0.01	0	-10000	0	-10000	0	0
GNA13	0.01	0	-10000	0	-10000	0	0
MMP9	-0.035	0.13	-10000	0	-0.45	13	13
MMP2	0.016	0.083	-10000	0	-0.5	3	3

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	0.024	0	-9999	-10000	0	0
SNTA1	0.006	0.048	-9999	-0.52	4	4
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.022	0.026	-9999	-0.3	3	3
MAPK12	0.012	0.057	-9999	-0.26	20	20
CCND1	0.007	0.056	-9999	-0.43	6	6
p38 gamma/SNTA1	0.015	0.059	-9999	-0.25	21	21
MAP2K3	0.01	0	-9999	-10000	0	0
PKN1	0.01	0	-9999	-10000	0	0
G2/M transition checkpoint	0.012	0.057	-9999	-0.26	20	20
MAP2K6	0.006	0.063	-9999	-0.3	20	20
MAPT	0.006	0.072	-9999	-0.29	24	24
MAPK13	0.018	0	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.013	0.015	-9999	-0.31	1	1

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.009	0.023	-10000	0	-10000	0	0
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	-0.002	0.078	0.52	2	-10000	0	2
IL27/IL27R/JAK1	-0.027	0.085	-10000	0	-0.76	2	2
TBX21	-0.001	0.14	-10000	0	-0.49	24	24
IL12B	0.004	0.053	-10000	0	-0.52	5	5
IL12A	0.004	0.041	-10000	0	-0.36	6	6
IL6ST	-0.008	0.094	-10000	0	-0.5	17	17
IL27RA/JAK1	0.011	0.056	-10000	0	-1.2	1	1
IL27	-0.005	0.083	-10000	0	-0.5	13	13
TYK2	0.011	0.004	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.064	0.12	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.002	0.078	0.52	2	-10000	0	2
T cell proliferation during immune response	-0.002	0.078	0.52	2	-10000	0	2
MAPKKK cascade	0.002	0.078	-10000	0	-0.52	2	2
STAT3	0.01	0	-10000	0	-10000	0	0
STAT2	0.01	0	-10000	0	-10000	0	0
STAT1	0.01	0.002	-10000	0	-10000	0	0
IL12RB1	-0.006	0.088	-10000	0	-0.5	15	15
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.009	0.16	-10000	0	-0.51	20	20
IL27/IL27R/JAK2/TYK2	0.002	0.079	-10000	0	-0.53	2	2
positive regulation of T cell mediated cytotoxicity	0.002	0.078	-10000	0	-0.52	2	2
STAT1 (dimer)	-0.046	0.13	0.48	1	-0.63	9	10
JAK2	0.008	0.033	-10000	0	-0.5	2	2
JAK1	0.01	0.002	-10000	0	-10000	0	0
STAT2 (dimer)	0.007	0.075	-10000	0	-0.5	2	2
T cell proliferation	-0.05	0.13	-10000	0	-0.45	16	16
IL12/IL12R/TYK2/JAK2	0.008	0.079	-10000	0	-0.6	2	2
IL17A	-0.064	0.12	-10000	0	-10000	0	0
mast cell activation	-0.002	0.078	0.52	2	-10000	0	2
IFNG	0.001	0.027	-10000	0	-0.12	9	9
T cell differentiation	-0.003	0.005	-10000	0	-0.021	20	20
STAT3 (dimer)	0.007	0.075	-10000	0	-0.5	2	2
STAT5A (dimer)	0.007	0.079	-10000	0	-0.61	2	2
STAT4 (dimer)	0.007	0.075	-10000	0	-0.5	2	2
STAT4	0.01	0	-10000	0	-10000	0	0
T cell activation	-0.006	0.006	0.12	1	-10000	0	1
IL27R/JAK2/TYK2	-0.011	0.074	-10000	0	-0.74	2	2
GATA3	0.003	0.082	-10000	0	-1.2	2	2
IL18	0.002	0.05	-10000	0	-0.36	9	9
positive regulation of mast cell cytokine production	0.007	0.074	-10000	0	-0.49	2	2
IL27/EBI3	-0.005	0.064	-10000	0	-0.36	15	15
IL27RA	0.001	0.058	-10000	0	-1.2	1	1
IL6	-0.11	0.21	-10000	0	-0.5	111	111
STAT5A	0.009	0.023	-10000	0	-0.5	1	1
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	0.003	0.022	0.46	1	-10000	0	1
IL1B	-0.012	0.086	-10000	0	-0.36	28	28
EBI3	0.007	0.033	-10000	0	-0.51	2	2
TNF	-0.005	0.071	-10000	0	-0.36	19	19

×

Ras signaling in the CD4+ TCR pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	0.019	0.1	-9999	-0.33	32	32
MAP3K8	0.008	0.033	-9999	-0.5	2	2
FOS	0.021	0.07	-9999	-0.37	5	5
PRKCA	0.008	0.033	-9999	-0.5	2	2
PTPN7	0.011	0.003	-9999	-10000	0	0
HRAS	0.01	0.001	-9999	-10000	0	0
PRKCB	-0.003	0.082	-9999	-0.5	13	13
NRAS	0.01	0.001	-9999	-10000	0	0
RAS family/GTP	-0.001	0.013	-9999	-0.3	1	1
MAPK3	0.02	0.041	-9999	-10000	0	0
MAP2K1	0.017	0.08	-9999	-0.41	15	15
ELK1	0.009	0.005	-9999	-10000	0	0
BRAF	-0.014	0.067	-9999	-0.39	15	15
mol:GTP	0	0.001	-9999	-0.005	32	32
MAPK1	0.02	0.041	-9999	-10000	0	0
RAF1	-0.014	0.067	-9999	-0.39	15	15
KRAS	0.009	0.024	-9999	-0.52	1	1

×

Sphingosine 1-phosphate (S1P) 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
SPHK2	0.009	0.023	-9999	-0.5	1	1
SPHK1	0.006	0.048	-9999	-0.52	4	4
GNAI2	0.01	0	-9999	-10000	0	0
mol:S1P	0.016	0.019	-9999	-0.27	1	1
GNAO1	0.004	0.057	-9999	-0.51	6	6
mol:Sphinganine-1-P	0.014	0.038	-9999	-0.36	5	5
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	-0.001	0.011	-9999	-10000	0	0
GNAI3	0.01	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
S1PR3	0.009	0.024	-9999	-0.52	1	1
S1PR2	0.01	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.001	0.015	-9999	-0.23	1	1
S1PR5	-0.026	0.13	-9999	-0.5	34	34
S1PR4	-0.017	0.11	-9999	-0.5	26	26
GNAI1	0.008	0.032	-9999	-0.5	2	2
S1P/S1P5/G12	-0.019	0.065	-9999	-0.25	34	34
S1P/S1P3/Gq	0.021	0.056	-9999	-0.27	14	14
S1P/S1P4/Gi	-0.001	0.089	-9999	-0.42	5	5
GNAQ	0.009	0.023	-9999	-0.5	1	1
GNAZ	-0.033	0.14	-9999	-0.5	41	41
GNA14	-0.005	0.085	-9999	-0.5	14	14
GNA15	0.01	0	-9999	-10000	0	0
GNA12	0.01	0	-9999	-10000	0	0
GNA13	0.01	0	-9999	-10000	0	0
GNA11	0.008	0.032	-9999	-0.5	2	2
ABCC1	0.01	0	-9999	-10000	0	0

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.008	0.032	-10000	0	-0.5	2	2
ANTXR2	0.009	0.023	-10000	0	-0.5	1	1
negative regulation of myeloid dendritic cell antigen processing and presentation	0	0.005	-10000	0	-0.066	3	3
monocyte activation	-0.005	0.092	-10000	0	-0.44	19	19
MAP2K2	0	0.002	-10000	0	-10000	0	0
MAP2K1	0	0.004	-10000	0	-10000	0	0
MAP2K7	0	0.004	-10000	0	-10000	0	0
MAP2K6	-0.011	0.052	-10000	0	-0.27	19	19
CYAA	0.011	0.021	-10000	0	-0.25	3	3
MAP2K4	0	0.004	-10000	0	-10000	0	0
IL1B	-0.002	0.064	-10000	0	-0.26	29	29
Channel	-0.002	0.021	-10000	0	-0.27	3	3
NLRP1	-0.001	0.017	-10000	0	-0.26	2	2
CALM1	0.01	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	0	0.006	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0	0.005	0.066	3	-10000	0	3
MAPK3	0	0.004	-10000	0	-10000	0	0
MAPK1	0	0.004	-10000	0	-10000	0	0
PGR	-0.045	0.098	-10000	0	-0.26	84	84
PA/Cellular Receptors	-0.002	0.023	-10000	0	-0.3	3	3
apoptosis	0	0.005	-10000	0	-0.066	3	3
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.011	0.021	-10000	0	-0.25	3	3
macrophage activation	0.015	0.005	-10000	0	-10000	0	0
TNF	-0.01	0.099	-10000	0	-0.5	19	19
VCAM1	-0.005	0.093	-10000	0	-0.44	19	19
platelet activation	0	0.006	-10000	0	-10000	0	0
MAPKKK cascade	-0.01	0.015	-10000	0	-10000	0	0
IL18	0.008	0.045	-10000	0	-0.31	9	9
negative regulation of macrophage activation	0	0.005	-10000	0	-0.066	3	3
LEF	0	0.005	-10000	0	-0.066	3	3
CASP1	-0.002	0.017	-10000	0	-0.22	2	2
mol:cAMP	0	0.006	-10000	0	-10000	0	0
necrosis	0	0.005	-10000	0	-0.066	3	3
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.002	0.02	-10000	0	-0.25	3	3
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.01	0	-10000	0	-10000	0	0
HDAC3	0.01	0	-10000	0	-10000	0	0
VDR	0.008	0.033	-10000	0	-0.51	2	2
Cbp/p300/PCAF	0	0	-10000	0	-10000	0	0
EP300	0.01	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.032	0.02	-10000	0	-10000	0	0
KAT2B	0.01	0	-10000	0	-10000	0	0
MAPK14	0.01	0	-10000	0	-10000	0	0
AKT1	0.016	0.027	0.2	1	-0.23	2	3
RAR alpha/9cRA/Cyclin H	-0.007	0.024	-10000	0	-10000	0	0
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.029	0.021	-10000	0	-10000	0	0
CDC2	0	0	-10000	0	-10000	0	0
response to UV	0.001	0	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.006	0.03	-10000	0	-10000	0	0
NCOR2	0.01	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	-0.002	0.023	-10000	0	-0.37	2	2
RXRs/RARs/NRIP1/9cRA	-0.013	0.068	-10000	0	-0.55	2	2
NCOA2	0.006	0.046	-10000	0	-0.5	4	4
NCOA3	0.01	0	-10000	0	-10000	0	0
NCOA1	0.01	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.008	0.033	-10000	0	-0.51	2	2
RARG	0.011	0	-10000	0	-10000	0	0
RAR gamma1/9cRA	0	0	-10000	0	-10000	0	0
MAPK3	0.011	0	-10000	0	-10000	0	0
MAPK1	0.01	0	-10000	0	-10000	0	0
MAPK8	0.011	0	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.045	0.058	-10000	0	-0.5	3	3
RARA	0.01	0.041	-10000	0	-0.23	2	2
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.028	0.028	-10000	0	-10000	0	0
PRKCA	0.011	0.033	-10000	0	-0.5	2	2
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.027	0.076	-10000	0	-0.59	2	2
RXRG	-0.17	0.18	-10000	0	-0.33	259	259
RXRA	0.017	0.038	-10000	0	-0.22	2	2
RXRB	0.002	0.062	-10000	0	-0.31	2	2
VDR/Vit D3/DNA	-0.002	0.023	-10000	0	-0.37	2	2
RBP1	0.003	0.058	-10000	0	-0.51	6	6
CRBP1/9-cic-RA	-0.005	0.041	-10000	0	-0.37	6	6
RARB	0.01	0.033	-10000	0	-0.5	2	2
PRKCG	-0.039	0.15	-10000	0	-0.51	46	46
MNAT1	0.01	0	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.014	0.067	-10000	0	-0.59	2	2
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.005	0.06	-10000	0	-0.45	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.03	0.03	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.027	0.076	-10000	0	-0.59	2	2
positive regulation of DNA binding	-0.007	0.023	-10000	0	-10000	0	0
NRIP1	-0.025	0.072	-10000	0	-0.54	2	2
RXRs/RARs	-0.034	0.078	-10000	0	-0.49	3	3
RXRs/RXRs/DNA/9cRA	-0.048	0.06	-10000	0	-0.61	2	2
PRKACA	0.01	0	-10000	0	-10000	0	0
CDK7	0.01	0	-10000	0	-10000	0	0
TFIIH	0	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.005	0.016	-10000	0	-10000	0	0
CCNH	0.01	0	-10000	0	-10000	0	0
CREBBP	0.01	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	0	0	-10000	0	-10000	0	0

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	0.004	0.056	-9999	-0.5	6	6
CLTC	0.01	0.047	-9999	-10000	0	0
calcium ion-dependent exocytosis	0.02	0.003	-9999	-10000	0	0
Dynamin 2/GTP	-0.027	0.081	-9999	-0.28	47	47
EXOC4	0.01	0	-9999	-10000	0	0
CD59	0.013	0.031	-9999	-10000	0	0
CPE	0.003	0.06	-9999	-0.31	17	17
CTNNB1	0.01	0	-9999	-10000	0	0
membrane fusion	0.021	0	-9999	-10000	0	0
CTNND1	-0.001	0.082	-9999	-0.25	47	47
DNM2	0.01	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.019	0.022	-9999	-10000	0	0
TSHR	-0.018	0.097	-9999	-0.31	48	48
INS	0.007	0.008	-9999	-10000	0	0
BIN1	0.01	0	-9999	-10000	0	0
mol:Choline	0.021	0	-9999	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-9999	-10000	0	0
mol:GDP	-0.017	0.096	-9999	-0.31	47	47
membrane depolarization	0	0	-9999	-10000	0	0
ARF6	0.01	0	-9999	-10000	0	0
mol:Ca2+	-0.026	0.081	-9999	-0.27	47	47
JUP	0.013	0.032	-9999	-10000	0	0
ASAP2/amphiphysin II	0	0	-9999	-10000	0	0
ARF6/GTP	0	0	-9999	-10000	0	0
CDH1	0.012	0.033	-9999	-10000	0	0
clathrin-independent pinocytosis	0	0	-9999	-10000	0	0
MAPK8IP3	0.008	0.034	-9999	-0.52	2	2
positive regulation of endocytosis	0	0	-9999	-10000	0	0
EXOC2	0.01	0	-9999	-10000	0	0
substrate adhesion-dependent cell spreading	0.034	0	-9999	-10000	0	0
insulin receptor binding	0	0	-9999	-10000	0	0
SPAG9	0.01	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.019	0.056	-9999	-10000	0	0
positive regulation of phagocytosis	0.015	0	-9999	-10000	0	0
ARF6/GTP/JIP3	-0.001	0.02	-9999	-0.31	2	2
ACAP1	0.02	0.008	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CHRM2	-0.027	0.088	-9999	-0.34	10	10
clathrin heavy chain/ACAP1	0.015	0.044	-9999	-10000	0	0
JIP4/KLC1	0	0	-9999	-10000	0	0
EXOC1	0.01	0	-9999	-10000	0	0
exocyst	0.034	0	-9999	-10000	0	0
RALA/GTP	0	0	-9999	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0	0	-9999	-10000	0	0
receptor recycling	0	0	-9999	-10000	0	0
CTNNA1	-0.001	0.082	-9999	-10000	0	0
NME1	-0.017	0.096	-9999	-0.31	47	47
clathrin coat assembly	0.01	0.047	-9999	-10000	0	0
IL2RA	0.003	0.047	-9999	-10000	0	0
VAMP3	0.015	0	-9999	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.013	0.043	-9999	-0.34	3	3
EXOC6	0.01	0	-9999	-10000	0	0
PLD1	0	0	-9999	-10000	0	0
PLD2	0	0	-9999	-10000	0	0
EXOC5	0.01	0	-9999	-10000	0	0
PIP5K1C	0.019	0.022	-9999	-10000	0	0
SDC1	0.013	0.031	-9999	-10000	0	0
ARF6/GDP	-0.017	0.096	-9999	-0.31	47	47
EXOC7	0.01	0	-9999	-10000	0	0
E-cadherin/beta catenin	-0.019	0.058	-9999	-10000	0	0
mol:Phosphatidic acid	0.021	0	-9999	-10000	0	0
endocytosis	0	0	-9999	-10000	0	0
SCAMP2	0.01	0	-9999	-10000	0	0
ADRB2	-0.081	0.14	-9999	-0.37	32	32
EXOC3	0.01	0	-9999	-10000	0	0
ASAP2	0.01	0	-9999	-10000	0	0
Dynamin 2/GDP	-0.009	0.087	-9999	-0.27	47	47
KLC1	0.01	0	-9999	-10000	0	0
AVPR2	-0.039	0.12	-9999	-0.37	16	16
RALA	0.01	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.017	0.051	-9999	-10000	0	0

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.063	0.18	-9999	-0.57	13	13
RAD9A	0.01	0	-9999	-10000	0	0
AP1	-0.016	0.096	-9999	-0.36	36	36
IFNAR2	0.008	0.005	-9999	-10000	0	0
AKT1	0.002	0.044	-9999	-0.22	6	6
ER alpha/Oestrogen	-0.015	0.082	-9999	-0.37	25	25
NFX1/SIN3/HDAC complex	0.028	0.018	-9999	-10000	0	0
EGF	-0.092	0.21	-9999	-0.52	92	92
SMG5	0.01	0	-9999	-10000	0	0
SMG6	0.01	0	-9999	-10000	0	0
SP3/HDAC2	0.012	0.009	-9999	-10000	0	0
TERT/c-Abl	-0.086	0.14	-9999	-0.56	11	11
SAP18	0.008	0.004	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	-0.034	0.14	-9999	-0.51	39	39
WRN	0.01	0	-9999	-10000	0	0
SP1	0.009	0.006	-9999	-10000	0	0
SP3	0.008	0.005	-9999	-10000	0	0
TERF2IP	0.01	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.079	0.12	-9999	-0.66	5	5
Mad/Max	0.011	0.008	-9999	-10000	0	0
TERT	-0.065	0.18	-9999	-0.6	12	12
CCND1	-0.058	0.19	-9999	-1.2	6	6
MAX	0.008	0.005	-9999	-10000	0	0
RBBP7	0.008	0.004	-9999	-10000	0	0
RBBP4	0.008	0.004	-9999	-10000	0	0
TERF2	0	0	-9999	-10000	0	0
PTGES3	0.01	0	-9999	-10000	0	0
SIN3A	0.008	0.004	-9999	-10000	0	0
Telomerase/911	0.022	0.029	-9999	-10000	0	0
CDKN1B	-0.004	0.087	-9999	-10000	0	0
RAD1	0.01	0	-9999	-10000	0	0
XRCC5	0.01	0	-9999	-10000	0	0
XRCC6	0.01	0	-9999	-10000	0	0
SAP30	0.008	0.004	-9999	-10000	0	0
TRF2/PARP2	0	0	-9999	-10000	0	0
UBE3A	0.007	0.005	-9999	-10000	0	0
JUN	0.004	0.046	-9999	-0.5	4	4
E6	-0.002	0.004	-9999	-10000	0	0
HPV-16 E6/E6AP	0.006	0.005	-9999	-10000	0	0
FOS	-0.026	0.13	-9999	-0.5	32	32
IFN-gamma/IRF1	-0.029	0.097	-9999	-0.36	40	40
PARP2	0.01	0	-9999	-10000	0	0
BLM	-0.042	0.16	-9999	-0.52	48	48
Telomerase	-0.021	0.058	-9999	-10000	0	0
IRF1	0.01	0.007	-9999	-10000	0	0
ESR1	-0.018	0.11	-9999	-0.51	25	25
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.03	0.02	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.03	0.02	-9999	-10000	0	0
HDAC1	0.008	0.004	-9999	-10000	0	0
HDAC2	0.009	0.006	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.02	0.004	-9999	-10000	0	0
ABL1	0.01	0	-9999	-10000	0	0
MXD1	0.008	0.005	-9999	-10000	0	0
MRE11A	0.01	0	-9999	-10000	0	0
HUS1	0.01	0	-9999	-10000	0	0
RPS6KB1	0.01	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.08	0.14	-9999	-0.61	7	7
NR2F2	0.013	0.007	-9999	-10000	0	0
MAPK3	0.011	0.008	-9999	-10000	0	0
MAPK1	0.011	0.008	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.011	0.002	-9999	-10000	0	0
NFKB1	0.01	0	-9999	-10000	0	0
HNRNPC	0.01	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0	0	-9999	-10000	0	0
NBN	0.01	0	-9999	-10000	0	0
EGFR	-0.007	0.087	-9999	-0.51	14	14
mol:Oestrogen	-0.001	0.002	-9999	-10000	0	0
EGF/EGFR	-0.08	0.16	-9999	-0.38	103	103
MYC	0.006	0.033	-9999	-0.5	2	2
IL2	0.004	0.011	-9999	-10000	0	0
KU	0	0	-9999	-10000	0	0
RAD50	0.01	0	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
TGFB1	0.011	0.002	-9999	-10000	0	0
TRF2/BLM	-0.033	0.1	-9999	-0.34	48	48
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.081	0.14	-9999	-0.64	7	7
SP1/HDAC2	0.013	0.011	-9999	-10000	0	0
PINX1	0.01	0	-9999	-10000	0	0
Telomerase/EST1A	-0.079	0.12	-9999	-0.66	5	5
Smad3/Myc	0.021	0.02	-9999	-0.29	2	2
911 complex	0	0	-9999	-10000	0	0
IFNG	-0.033	0.14	-9999	-0.51	40	40
Telomerase/PinX1	-0.079	0.12	-9999	-0.66	5	5
Telomerase/AKT1/mTOR/p70S6K	0.006	0.054	-9999	-10000	0	0
SIN3B	0.008	0.004	-9999	-10000	0	0
YWHAE	0.01	0	-9999	-10000	0	0
Telomerase/EST1B	-0.079	0.12	-9999	-0.66	5	5
response to DNA damage stimulus	0.003	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0	0	-9999	-10000	0	0
TRF2/WRN	0	0	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.079	0.12	-9999	-0.66	5	5
E2F1	0.001	0.064	-9999	-0.52	7	7
ZNFX1	0.008	0.004	-9999	-10000	0	0
PIF1	-0.064	0.18	-9999	-0.52	68	68
NCL	0.01	0	-9999	-10000	0	0
DKC1	0.01	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

Insulin Pathway

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
CBL/APS/CAP	-0.013	0.054	-9999	-0.46	1	1
TC10/GTP	-0.012	0.051	-9999	-0.44	1	1
Insulin Receptor/Insulin/IRS1/Shp2	-0.001	0.012	-9999	-10000	0	0
HRAS	0.01	0	-9999	-10000	0	0
APS homodimer	0.009	0.023	-9999	-0.5	1	1
GRB14	-0.026	0.13	-9999	-0.51	33	33
FOXO3	-0.005	0.04	-9999	-0.6	2	2
AKT1	0.024	0.062	-9999	-10000	0	0
INSR	0.011	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.01	0	-9999	-10000	0	0
SORBS1	-0.018	0.12	-9999	-0.5	27	27
CRK	0.01	0	-9999	-10000	0	0
PTPN1	0.028	0	-9999	-10000	0	0
CAV1	-0.15	0.13	-9999	-0.25	313	313
CBL/APS/CAP/Crk-II/C3G	-0.014	0.057	-9999	-0.49	1	1
Insulin Receptor/Insulin/IRS1/NCK2	-0.001	0.012	-9999	-0.27	1	1
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.015	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.03	0.012	-9999	-10000	0	0
RPS6KB1	0.029	0.058	-9999	-10000	0	0
PARD6A	0.009	0.023	-9999	-0.5	1	1
CBL	0.01	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0.001	-9999	-10000	0	0
PIK3R1	0.009	0.023	-9999	-0.5	1	1
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.012	0.045	-9999	-10000	0	0
HRAS/GTP	-0.002	0.019	-9999	-10000	0	0
Insulin Receptor	0.011	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.001	0.016	-9999	-10000	0	0
PRKCI	-0.004	0.013	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.015	0.056	-9999	-10000	0	0
SHC1	0.009	0.024	-9999	-0.52	1	1
negative regulation of MAPKKK cascade	0	0.002	-9999	-10000	0	0
PI3K	-0.001	0.015	-9999	-10000	0	0
NCK2	0.01	0	-9999	-10000	0	0
RHOQ	0.01	0	-9999	-10000	0	0
mol:H2O2	0	0	-9999	-10000	0	0
HRAS/GDP	0	0	-9999	-10000	0	0
AKT2	0.024	0.062	-9999	-10000	0	0
PRKCZ	-0.007	0.037	-9999	-0.45	3	3
SH2B2	0.009	0.023	-9999	-0.5	1	1
SHC/SHIP	0.024	0.026	-9999	-10000	0	0
F2RL2	-0.031	0.14	-9999	-0.52	38	38
TRIP10	0.01	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	-0.001	0.013	-9999	-0.29	1	1
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	-0.001	0.012	-9999	-10000	0	0
RAPGEF1	0.01	0	-9999	-10000	0	0
RASA1	0.01	0	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	-0.015	0.062	-9999	-0.27	27	27
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	-0.001	0.013	-9999	-0.28	1	1
INPP5D	0.019	0.024	-9999	-0.25	4	4
SOS1	0.01	0	-9999	-10000	0	0
SGK1	-0.005	0.054	-9999	-0.85	2	2
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.01	0	-9999	-10000	0	0
IRS1	0.009	0.023	-9999	-0.5	1	1
p62DOK/RasGAP	0	0.002	-9999	-10000	0	0
INS	0.002	0	-9999	-10000	0	0
mol:PI-3-4-P2	0.019	0.024	-9999	-0.25	4	4
GRB2	0.01	0	-9999	-10000	0	0
EIF4EBP1	0.021	0.075	-9999	-0.42	3	3
PTPRA	0.011	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0.01	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.026	0.013	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1	-0.001	0.012	-9999	-0.28	1	1
Insulin Receptor/Insulin/IRS3	0	0	-9999	-10000	0	0
Par3/Par6	-0.02	0.068	-9999	-10000	0	0

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.025	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP1	0	0	-9999	-10000	0	0
mol:DAG	0.021	0.054	-9999	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	0	0	-9999	-10000	0	0
CaM/Ca2+	0.026	0.051	-9999	-10000	0	0
HIF1A	0.016	0	-9999	-10000	0	0
GAB1	0.007	0.04	-9999	-0.5	3	3
AKT1	0.038	0.045	-9999	-10000	0	0
PLCG1	0.022	0.054	-9999	-10000	0	0
NOS3	0.038	0.053	-9999	-10000	0	0
CBL	0.01	0	-9999	-10000	0	0
mol:NO	0.038	0.052	-9999	-10000	0	0
FLT1	0.024	0	-9999	-10000	0	0
PGF	-0.008	0.097	-9999	-0.52	17	17
VEGFR1 homodimer/NRP2/VEGFR121	-0.002	0.02	-9999	-10000	0	0
CALM1	0.01	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
eNOS/Hsp90	0.042	0.051	-9999	-10000	0	0
endothelial cell proliferation	0.029	0.06	-9999	-0.38	3	3
mol:Ca2+	0.021	0.054	-9999	-10000	0	0
MAPK3	0.031	0.053	-9999	-0.46	1	1
MAPK1	0.031	0.053	-9999	-0.46	1	1
PIK3R1	0.009	0.023	-9999	-0.5	1	1
PLGF homodimer	-0.008	0.097	-9999	-0.52	17	17
PRKACA	0.01	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.32	0.24	-9999	-0.5	313	313
VEGFA homodimer	0.01	0	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0.025	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.036	0.051	-9999	-0.44	1	1
PI3K	-0.009	0.045	-9999	-10000	0	0
PRKCA	0.026	0.055	-9999	-0.49	1	1
PRKCB	0.02	0.069	-9999	-0.49	2	2
VEGFR1 homodimer/PLGF homodimer	0.014	0.06	-9999	-10000	0	0
VEGFA	0.01	0	-9999	-10000	0	0
VEGFB	0.01	0	-9999	-10000	0	0
mol:IP3	0.021	0.054	-9999	-10000	0	0
RASA1	0.032	0	-9999	-10000	0	0
NRP2	0.007	0.04	-9999	-0.5	3	3
VEGFR1 homodimer	0.024	0	-9999	-10000	0	0
VEGFB homodimer	0.01	0	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.11	0.12	-9999	-0.4	12	12
PTPN11	0.01	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.009	0.045	-9999	-10000	0	0
mol:L-citrulline	0.038	0.052	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0	0	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	0	0	-9999	-10000	0	0
CD2AP	0.01	0	-9999	-10000	0	0
PI3K/GAB1	-0.01	0.045	-9999	-10000	0	0
PDPK1	0.03	0.049	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/SHP2	0	0	-9999	-10000	0	0
mol:NADP	0.038	0.052	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP2	0.024	0.024	-9999	-10000	0	0

×

p38 MAPK 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0	0	-10000	0	-10000	0	0
TRAF2/ASK1	0	0	-10000	0	-10000	0	0
ATM	0.01	0	-10000	0	-10000	0	0
MAP2K3	0.021	0.026	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.025	0.031	-10000	0	-10000	0	0
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.004	0.057	-10000	0	-0.5	6	6
TXN	0.006	0.013	-10000	0	-0.2	2	2
CALM1	0.01	0	-10000	0	-10000	0	0
GADD45A	0.008	0.033	-10000	0	-0.51	2	2
GADD45B	0.005	0.051	-10000	0	-0.5	5	5
MAP3K1	0.01	0	-10000	0	-10000	0	0
MAP3K6	0.01	0	-10000	0	-10000	0	0
MAP3K7	0.01	0	-10000	0	-10000	0	0
MAP3K4	0.01	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0	0	-10000	0	-10000	0	0
TAK1/TAB family	0.001	0.013	0.17	3	-10000	0	3
RAC1/OSM/MEKK3	-0.001	0.012	-10000	0	-0.26	1	1
TRAF2	0.01	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.003	0.009	-10000	0	-10000	0	0
TRAF6	0.007	0	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.082	0.2	-10000	0	-0.52	85	85
CCM2	0.01	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.054	0.12	-10000	0	-0.31	85	85
MAPK11	0.007	0.04	-10000	0	-0.5	3	3
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.048	0.1	-10000	0	-0.28	85	85
OSM/MEKK3	-0.001	0.016	-10000	0	-0.35	1	1
TAOK1	0.013	0.015	-10000	0	-0.31	1	1
TAOK2	0.014	0	-10000	0	-10000	0	0
TAOK3	0.014	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.01	0	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.01	0	-10000	0	-10000	0	0
MAP3K10	0.007	0.04	-10000	0	-0.5	3	3
MAP3K3	0.009	0.023	-10000	0	-0.5	1	1
TRX/ASK1	0.012	0.011	-10000	0	-10000	0	0
GADD45/MTK1/MTK1	-0.007	0.046	-10000	0	-0.38	4	4

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	-0.001	0.016	-9999	-0.26	2	2
HDAC3	0.01	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.001	0.014	-9999	-10000	0	0
GATA1/HDAC4	-0.038	0.11	-9999	-0.35	53	53
GATA1/HDAC5	-0.037	0.11	-9999	-0.35	52	52
GATA2/HDAC5	-0.03	0.098	-9999	-0.35	41	41
HDAC5/BCL6/BCoR	0	0	-9999	-10000	0	0
HDAC9	-0.003	0.08	-9999	-0.51	12	12
Glucocorticoid receptor/Hsp90/HDAC6	-0.001	0.014	-9999	-0.3	1	1
HDAC4/ANKRA2	-0.001	0.017	-9999	-0.37	1	1
HDAC5/YWHAB	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.017	0	-9999	-10000	0	0
GATA2	-0.033	0.14	-9999	-0.5	41	41
HDAC4/RFXANK	-0.001	0.017	-9999	-0.37	1	1
BCOR	0.01	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.009	0.023	-9999	-0.5	1	1
HDAC5	0.01	0	-9999	-10000	0	0
GNB1/GNG2	-0.001	0.022	-9999	-0.35	2	2
Histones	0.027	0.031	-9999	-10000	0	0
ADRBK1	0.01	0	-9999	-10000	0	0
HDAC4	0.009	0.024	-9999	-0.52	1	1
XPO1	0.01	0	-9999	-10000	0	0
HDAC5/ANKRA2	0	0	-9999	-10000	0	0
HDAC4/Ubc9	-0.001	0.017	-9999	-0.37	1	1
HDAC7	0.01	0	-9999	-10000	0	0
HDAC5/14-3-3 E	0	0	-9999	-10000	0	0
TUBA1B	0.01	0	-9999	-10000	0	0
HDAC6	0.009	0.024	-9999	-0.52	1	1
HDAC5/RFXANK	0	0	-9999	-10000	0	0
CAMK4	0	0.069	-9999	-0.5	9	9
Tubulin/HDAC6	-0.009	0.053	-9999	-0.3	15	15
SUMO1	0.01	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.01	0	-9999	-10000	0	0
GATA1	-0.046	0.16	-9999	-0.5	52	52
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.01	0	-9999	-10000	0	0
NR3C1	0.01	0	-9999	-10000	0	0
SUMO1/HDAC4	0.023	0.012	-9999	-0.24	1	1
SRF	0.01	0	-9999	-10000	0	0
HDAC4/YWHAB	-0.001	0.017	-9999	-0.37	1	1
Tubulin	-0.011	0.061	-9999	-0.37	14	14
HDAC4/14-3-3 E	-0.001	0.017	-9999	-0.37	1	1
GNB1	0.01	0	-9999	-10000	0	0
RANGAP1	0.01	0	-9999	-10000	0	0
BCL6/BCoR	0	0	-9999	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	-0.001	0.014	-9999	-0.3	1	1
HDAC4/SRF	-0.006	0.042	-9999	-0.29	10	10
HDAC4/ER alpha	-0.019	0.081	-9999	-0.36	26	26
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.027	0.031	-9999	-10000	0	0
cell motility	-0.009	0.052	-9999	-0.3	15	15
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.01	0	-9999	-10000	0	0
HDAC7/HDAC3	0	0	-9999	-10000	0	0
BCL6	0.01	0	-9999	-10000	0	0
HDAC4/CaMK II delta B	0.009	0.024	-9999	-0.52	1	1
Hsp90/HDAC6	-0.001	0.017	-9999	-0.37	1	1
ESR1	-0.017	0.11	-9999	-0.51	25	25
HDAC6/HDAC11	-0.001	0.017	-9999	-0.37	1	1
Ran/GTP/Exportin 1	0	0.01	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
MEF2C	0.01	0	-9999	-10000	0	0
RAN	0.009	0.024	-9999	-0.52	1	1
HDAC4/MEF2C	-0.001	0.011	-9999	-10000	0	0
GNG2	0.008	0.032	-9999	-0.5	2	2
NCOR2	0.01	0	-9999	-10000	0	0
TUBB2A	-0.005	0.088	-9999	-0.52	14	14
HDAC11	0.01	0	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
RANBP2	0.01	0	-9999	-10000	0	0
ANKRA2	0.01	0	-9999	-10000	0	0
RFXANK	0.01	0	-9999	-10000	0	0
nuclear import	0	0.009	-9999	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.013	0.073	-9999	-0.64	4	4
MAP4K1	0.005	0.051	-9999	-0.5	5	5
MAP3K8	0.008	0.032	-9999	-0.5	2	2
PRKCB	-0.004	0.082	-9999	-0.5	13	13
DBNL	0.01	0	-9999	-10000	0	0
CRKL	0.01	0	-9999	-10000	0	0
MAP3K1	0.025	0.069	-9999	-0.6	4	4
JUN	0.011	0.11	-9999	-0.62	13	13
MAP3K7	0.025	0.069	-9999	-0.6	4	4
GRAP2	-0.006	0.088	-9999	-0.5	15	15
CRK	0.01	0	-9999	-10000	0	0
MAP2K4	0.031	0.075	-9999	-0.67	4	4
LAT	0.009	0.024	-9999	-0.52	1	1
LCP2	0.007	0.04	-9999	-0.5	3	3
MAPK8	0.007	0.11	-9999	-0.64	13	13
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.02	0.073	-9999	-0.64	4	4
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.012	0.068	-9999	-0.61	4	4

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.01	0.001	-9999	-10000	0	0
HDAC2	0.01	0.001	-9999	-10000	0	0
GNB1/GNG2	-0.004	0.033	-9999	-0.3	6	6
forebrain development	-0.013	0.14	-9999	-0.53	18	18
GNAO1	0.003	0.057	-9999	-0.51	6	6
SMO/beta Arrestin2	0.012	0.035	-9999	-0.37	4	4
SMO	0.005	0.048	-9999	-0.52	4	4
ARRB2	0.009	0.004	-9999	-10000	0	0
GLI3/SPOP	0.034	0.036	-9999	-10000	0	0
mol:GTP	-0.001	0.003	-9999	-10000	0	0
GSK3B	0.01	0	-9999	-10000	0	0
GNAI2	0.009	0.004	-9999	-10000	0	0
SIN3/HDAC complex	0.006	0.013	-9999	-10000	0	0
GNAI1	0.007	0.033	-9999	-0.5	2	2
XPO1	0.011	0.005	-9999	-10000	0	0
GLI1/Su(fu)	-0.045	0.11	-9999	-0.53	12	12
SAP30	0.01	0.001	-9999	-10000	0	0
mol:GDP	0.005	0.047	-9999	-0.51	4	4
MIM/GLI2A	0.003	0.04	-9999	-0.53	1	1
IFT88	0.01	0	-9999	-10000	0	0
GNAI3	0.009	0.004	-9999	-10000	0	0
GLI2	0.036	0.012	-9999	-10000	0	0
GLI3	0.03	0.038	-9999	-10000	0	0
CSNK1D	0.01	0	-9999	-10000	0	0
CSNK1E	0.01	0	-9999	-10000	0	0
SAP18	0.01	0.001	-9999	-10000	0	0
embryonic digit morphogenesis	0.01	0	-9999	-10000	0	0
GNG2	0.008	0.032	-9999	-0.5	2	2
Gi family/GTP	0.001	0.079	-9999	-0.27	20	20
SIN3B	0.01	0.001	-9999	-10000	0	0
SIN3A	0.01	0.001	-9999	-10000	0	0
GLI3/Su(fu)	0.038	0.033	-9999	-10000	0	0
GLI2/Su(fu)	0.04	0.027	-9999	-10000	0	0
FOXA2	-0.17	0.39	-9999	-1	82	82
neural tube patterning	-0.013	0.14	-9999	-0.53	18	18
SPOP	0.01	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.021	0.017	-9999	-10000	0	0
GNB1	0.01	0	-9999	-10000	0	0
CSNK1G2	0.01	0	-9999	-10000	0	0
CSNK1G3	0.01	0	-9999	-10000	0	0
MTSS1	0.003	0.04	-9999	-0.53	1	1
embryonic limb morphogenesis	-0.013	0.14	-9999	-0.53	18	18
SUFU	0.019	0.018	-9999	-10000	0	0
LGALS3	0.01	0	-9999	-10000	0	0
catabolic process	0.054	0.034	-9999	-10000	0	0
GLI3A/CBP	0.005	0.055	-9999	-0.33	12	12
KIF3A	0.01	0	-9999	-10000	0	0
GLI1	-0.014	0.14	-9999	-0.55	18	18
RAB23	0.01	0	-9999	-10000	0	0
CSNK1A1	0.01	0	-9999	-10000	0	0
IFT172	0.01	0	-9999	-10000	0	0
RBBP7	0.01	0.001	-9999	-10000	0	0
Su(fu)/Galectin3	0.021	0.017	-9999	-10000	0	0
GNAZ	-0.034	0.14	-9999	-0.5	41	41
RBBP4	0.01	0.001	-9999	-10000	0	0
CSNK1G1	0.01	0	-9999	-10000	0	0
PIAS1	0.01	0	-9999	-10000	0	0
PRKACA	0.01	0	-9999	-10000	0	0
GLI2/SPOP	0.038	0.011	-9999	-10000	0	0
STK36	0.01	0.005	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.008	0.074	-9999	-0.5	2	2
PTCH1	-0.012	0.17	-9999	-0.86	12	12
MIM/GLI1	-0.044	0.22	-9999	-0.49	87	87
CREBBP	0.005	0.055	-9999	-0.33	12	12
Su(fu)/SIN3/HDAC complex	0.041	0.007	-9999	-10000	0	0

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.01	0.055	-10000	0	-0.35	11	11
MAP4K4	0.029	0.042	-10000	0	-10000	0	0
BAG4	0.009	0.024	-10000	0	-0.52	1	1
PKC zeta/ceramide	-0.011	0.034	0.13	5	-0.24	2	7
NFKBIA	0.01	0	-10000	0	-10000	0	0
BIRC3	0.004	0.057	-10000	0	-0.51	6	6
BAX	-0.002	0.016	-10000	0	-10000	0	0
RIPK1	0.01	0	-10000	0	-10000	0	0
AKT1	0.017	0.007	-10000	0	-10000	0	0
BAD	-0.009	0.032	0.14	6	-10000	0	6
SMPD1	0.017	0.036	-10000	0	-0.16	18	18
RB1	-0.009	0.032	0.14	6	-10000	0	6
FADD/Caspase 8	0.036	0.045	-10000	0	-0.45	1	1
MAP2K4	-0.003	0.03	-10000	0	-10000	0	0
NSMAF	0.01	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.003	0.03	-10000	0	-10000	0	0
EGF	-0.089	0.21	-10000	0	-0.52	92	92
mol:ceramide	-0.017	0.034	0.14	6	-10000	0	6
MADD	0.01	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.01	0.055	-10000	0	-0.35	11	11
ASAH1	0.009	0.023	-10000	0	-0.5	1	1
negative regulation of cell cycle	-0.009	0.031	0.14	6	-10000	0	6
cell proliferation	-0.01	0.03	-10000	0	-10000	0	0
BID	0.02	0.033	-10000	0	-10000	0	0
MAP3K1	-0.009	0.032	0.14	6	-10000	0	6
EIF2A	0.003	0.029	-10000	0	-10000	0	0
TRADD	0.01	0	-10000	0	-10000	0	0
CRADD	0.009	0.024	-10000	0	-0.52	1	1
MAPK3	0.006	0.028	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.006	0.028	-10000	0	-10000	0	0
Cathepsin D/ceramide	-0.01	0.031	0.13	6	-10000	0	6
FADD	0.029	0.042	-10000	0	-10000	0	0
KSR1	-0.009	0.032	0.14	6	-10000	0	6
MAPK8	-0.001	0.032	0.14	5	-0.2	2	7
PRKRA	-0.009	0.032	0.14	6	-10000	0	6
PDGFA	0	0.072	-10000	0	-0.5	10	10
TRAF2	0.01	0	-10000	0	-10000	0	0
IGF1	-0.002	0.076	-10000	0	-0.5	11	11
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.017	0.034	0.14	6	-10000	0	6
CTSD	0.01	0	-10000	0	-10000	0	0
regulation of nitric oxide biosynthetic process	0	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	0.008	0.039	-10000	0	-10000	0	0
PRKCD	0.01	0	-10000	0	-10000	0	0
PRKCZ	0.007	0.04	-10000	0	-0.5	3	3
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.01	0.055	-10000	0	-0.35	11	11
RelA/NF kappa B1	0	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.01	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.024	0.045	-10000	0	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.012	0.058	-10000	0	-0.29	20	20
mol:Sphingosine-1-phosphate	0.01	0.055	-10000	0	-0.35	11	11
MAP2K1	0.003	0.029	-10000	0	-10000	0	0
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.01	0	-10000	0	-10000	0	0
CYCS	-0.004	0.024	0.15	1	-10000	0	1
TNFRSF1A	0.01	0	-10000	0	-10000	0	0
NFKB1	0.01	0	-10000	0	-10000	0	0
TNFR1A/BAG4	-0.001	0.017	-10000	0	-0.37	1	1
EIF2AK2	-0.003	0.03	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.011	0.056	-10000	0	-0.29	19	19
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.028	0.038	-10000	0	-0.58	1	1
MAP2K2	0.003	0.029	-10000	0	-10000	0	0
SMPD3	0.016	0.042	-10000	0	-0.29	1	1
TNF	-0.01	0.099	-10000	0	-0.5	19	19
PKC zeta/PAR4	-0.002	0.027	-10000	0	-0.35	3	3
mol:PHOSPHOCHOLINE	0.022	0.067	0.15	92	-10000	0	92
NF kappa B1/RelA/I kappa B alpha	-0.001	0.018	-10000	0	-10000	0	0
AIFM1	-0.004	0.024	0.15	1	-10000	0	1
BCL2	0.007	0.041	-10000	0	-0.51	3	3

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

Figure S99. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S99. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.01	0	-10000	0	-10000	0	0
NFATC1	0.036	0.04	-10000	0	-0.4	1	1
NFATC2	0.013	0.044	-10000	0	-0.26	2	2
NFATC3	0.013	0.031	-10000	0	-0.37	3	3
YWHAE	0.01	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.016	0.097	-10000	0	-0.36	18	18
Exportin 1/Ran/NUP214	-0.001	0.014	-10000	0	-0.3	1	1
mol:DAG	-0.001	0.003	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.035	0.082	-10000	0	-0.39	15	15
BCL2/BAX	-0.002	0.028	-10000	0	-0.36	3	3
CaM/Ca2+/Calcineurin A alpha-beta B1	0.005	0.007	-10000	0	-10000	0	0
CaM/Ca2+	0.005	0.007	-10000	0	-10000	0	0
BAX	0.01	0	-10000	0	-10000	0	0
MAPK14	0.008	0.004	-10000	0	-10000	0	0
BAD	0.01	0	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.011	0.092	-10000	0	-0.34	18	18
Calcineurin A alpha-beta B1/BCL2	0.007	0.041	-10000	0	-0.51	3	3
FKBP8	0.009	0.023	-10000	0	-0.5	1	1
activation-induced cell death of T cells	0.011	0.091	0.34	18	-10000	0	18
KPNB1	0.01	0	-10000	0	-10000	0	0
KPNA2	0.002	0.063	-10000	0	-0.52	7	7
XPO1	0.01	0.001	-10000	0	-10000	0	0
SFN	0	0.071	-10000	0	-0.52	9	9
MAP3K8	0.006	0.033	-10000	0	-0.5	2	2
NFAT4/CK1 alpha	-0.001	0.016	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.052	0.099	-10000	0	-0.39	5	5
CABIN1	-0.016	0.098	-10000	0	-0.37	18	18
CALM1	0.008	0.004	-10000	0	-10000	0	0
RAN	0.009	0.024	-10000	0	-0.52	1	1
MAP3K1	0.01	0	-10000	0	-10000	0	0
CAMK4	0	0.069	-10000	0	-0.5	9	9
mol:Ca2+	-0.002	0.007	-10000	0	-10000	0	0
MAPK3	0.01	0	-10000	0	-10000	0	0
YWHAH	0.01	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.002	0.028	-10000	0	-0.35	3	3
YWHAB	0.01	0	-10000	0	-10000	0	0
MAPK8	0.008	0.004	-10000	0	-10000	0	0
MAPK9	0.01	0	-10000	0	-10000	0	0
YWHAG	0.01	0	-10000	0	-10000	0	0
FKBP1A	0.01	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	-0.003	0.035	-10000	0	-0.34	3	3
PRKCH	0.01	0	-10000	0	-10000	0	0
CABIN1/Cbp/p300	-0.002	0.004	-10000	0	-10000	0	0
CASP3	0.008	0.004	-10000	0	-10000	0	0
PIM1	0.01	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0	-10000	0	-10000	0	0
apoptosis	0	0.014	0.21	1	-10000	0	1
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.031	0.016	-10000	0	-10000	0	0
PRKCB	-0.004	0.082	-10000	0	-0.5	13	13
PRKCE	0.005	0.051	-10000	0	-0.5	5	5
JNK2/NFAT4	0.016	0.029	-10000	0	-0.33	3	3
BAD/BCL-XL	0	0	-10000	0	-10000	0	0
PRKCD	0.01	0	-10000	0	-10000	0	0
NUP214	0.01	0.001	-10000	0	-10000	0	0
PRKCZ	0.005	0.04	-10000	0	-0.5	3	3
PRKCA	0.008	0.032	-10000	0	-0.5	2	2
PRKCG	-0.042	0.15	-10000	0	-0.52	46	46
PRKCQ	-0.067	0.18	-10000	0	-0.5	74	74
FKBP38/BCL2	-0.003	0.032	-10000	0	-0.36	4	4
EP300	0.008	0.005	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.01	0	-10000	0	-10000	0	0
NFATc/JNK1	0.035	0.041	-10000	0	-0.38	1	1
CaM/Ca2+/FKBP38	-0.001	0.014	-10000	0	-0.31	1	1
FKBP12/FK506	0	0	-10000	0	-10000	0	0
CSNK1A1	0.012	0.009	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.005	0.04	-10000	0	-0.3	9	9
NFATc/ERK1	0.04	0.038	-10000	0	-0.38	1	1
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.034	0.081	-10000	0	-0.39	15	15
NR4A1	-0.053	0.21	-10000	0	-0.47	97	97
GSK3B	0.008	0.004	-10000	0	-10000	0	0
positive T cell selection	0.013	0.031	-10000	0	-0.37	3	3
NFAT1/CK1 alpha	-0.011	0.025	-10000	0	-0.26	1	1
RCH1/ KPNB1	-0.005	0.044	-10000	0	-0.37	7	7
YWHAQ	0.01	0	-10000	0	-10000	0	0
PRKACA	0.008	0.004	-10000	0	-10000	0	0
AKAP5	0.007	0.04	-10000	0	-0.5	3	3
MEF2D	0.008	0.005	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.01	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.035	0.041	-10000	0	-0.38	1	1
CREBBP	0.008	0.005	-10000	0	-10000	0	0
BCL2	0.007	0.041	-10000	0	-0.51	3	3

×

FoxO family signaling

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
G6PC	0.016	0.048	-9999	-10000	0	0
PLK1	-0.13	0.26	-9999	-0.6	47	47
CDKN1B	0.014	0.11	-9999	-10000	0	0
FOXO3	-0.073	0.21	-9999	-0.52	44	44
KAT2B	0.004	0.019	-9999	-10000	0	0
FOXO1/SIRT1	0.014	0.029	-9999	-10000	0	0
CAT	-0.071	0.24	-9999	-1.3	7	7
CTNNB1	0.01	0	-9999	-10000	0	0
AKT1	0.005	0.02	-9999	-10000	0	0
FOXO1	0.021	0.029	-9999	-10000	0	0
MAPK10	-0.005	0.088	-9999	-0.25	54	54
mol:GTP	0.002	0	-9999	-10000	0	0
FOXO4	0.052	0.064	-9999	-10000	0	0
response to oxidative stress	-0.008	0.024	-9999	-10000	0	0
FOXO3A/SIRT1	-0.12	0.16	-9999	-0.49	42	42
XPO1	0.011	0	-9999	-10000	0	0
EP300	0.01	0.004	-9999	-10000	0	0
BCL2L11	0.008	0.032	-9999	-10000	0	0
FOXO1/SKP2	0.021	0.037	-9999	-0.28	2	2
mol:GDP	-0.008	0.024	-9999	-10000	0	0
RAN	0.01	0.024	-9999	-0.52	1	1
GADD45A	0.008	0.12	-9999	-0.71	2	2
YWHAQ	0.01	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.055	0.016	-9999	-10000	0	0
MST1	-0.013	0.094	-9999	-0.53	15	15
CSNK1D	0.01	0	-9999	-10000	0	0
CSNK1E	0.01	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.042	0.021	-9999	-10000	0	0
YWHAB	0.01	0	-9999	-10000	0	0
MAPK8	0.025	0.01	-9999	-10000	0	0
MAPK9	0.025	0.01	-9999	-10000	0	0
YWHAG	0.01	0	-9999	-10000	0	0
YWHAE	0.01	0	-9999	-10000	0	0
YWHAZ	0.01	0	-9999	-10000	0	0
SIRT1	0.007	0.009	-9999	-10000	0	0
SOD2	0.012	0.14	-9999	-10000	0	0
RBL2	-0.023	0.15	-9999	-0.49	4	4
RAL/GDP	0.013	0.015	-9999	-10000	0	0
CHUK	0.004	0.019	-9999	-10000	0	0
Ran/GTP	0.01	0.017	-9999	-0.37	1	1
CSNK1G2	0.01	0	-9999	-10000	0	0
RAL/GTP	0.019	0.015	-9999	-10000	0	0
CSNK1G1	0.01	0	-9999	-10000	0	0
FASLG	-0.008	0.15	-9999	-1.3	6	6
SKP2	0.006	0.048	-9999	-0.52	4	4
USP7	0.011	0.001	-9999	-10000	0	0
IKBKB	0.004	0.019	-9999	-10000	0	0
CCNB1	-0.1	0.25	-9999	-0.6	45	45
FOXO1-3a-4/beta catenin	-0.035	0.074	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.021	0.037	-9999	-0.28	2	2
CSNK1A1	0.01	0	-9999	-10000	0	0
SGK1	0.002	0.039	-9999	-0.52	2	2
CSNK1G3	0.01	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.018	0.015	-9999	-0.31	1	1
ZFAND5	0.055	0.057	-9999	-10000	0	0
SFN	0	0.071	-9999	-0.52	9	9
CDK2	0.01	0.006	-9999	-10000	0	0
FOXO3A/14-3-3	0.022	0.047	-9999	-0.37	1	1
CREBBP	0.01	0.006	-9999	-10000	0	0
FBXO32	-0.081	0.22	-9999	-0.6	37	37
BCL6	-0.023	0.15	-9999	-0.49	4	4
RALB	0.011	0	-9999	-10000	0	0
RALA	0.011	0	-9999	-10000	0	0
YWHAH	0.01	0	-9999	-10000	0	0

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	0.024	0.016	-10000	0	-0.22	2	2
epithelial cell differentiation	-0.001	0.015	-10000	0	-0.24	2	2
CYFIP2	0.003	0.06	-10000	0	-0.5	7	7
ENAH	0.048	0.031	-10000	0	-10000	0	0
EGFR	-0.005	0.086	-10000	0	-0.51	14	14
EPHA2	0	0.072	-10000	0	-0.5	10	10
MYO6	0.029	0.016	-10000	0	-10000	0	0
CTNNB1	0.01	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.004	0.035	-10000	0	-0.29	7	7
AQP5	-0.1	0.17	-10000	0	-0.42	108	108
CTNND1	0.01	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.029	0.016	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.11	0.13	-10000	0	-0.46	1	1
EGF	-0.089	0.21	-10000	0	-0.52	92	92
NCKAP1	0.01	0	-10000	0	-10000	0	0
AQP3	-0.017	0.084	-10000	0	-0.44	18	18
cortical microtubule organization	-0.001	0.015	-10000	0	-0.24	2	2
GO:0000145	0.028	0.015	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.001	0.015	-10000	0	-0.24	2	2
MLLT4	0.01	0	-10000	0	-10000	0	0
ARF6/GDP	-0.005	0.032	-10000	0	-0.39	1	1
ARF6	0.01	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.006	0.038	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.037	0.02	-10000	0	-10000	0	0
PVRL2	0.01	0	-10000	0	-10000	0	0
ZYX	0.029	0.02	-10000	0	-10000	0	0
ARF6/GTP	-0.005	0.034	-10000	0	-10000	0	0
CDH1	0.008	0.032	-10000	0	-0.5	2	2
EGFR/EGFR/EGF/EGF	-0.049	0.096	-10000	0	-0.46	3	3
RhoA/GDP	-0.001	0.014	-10000	0	-10000	0	0
actin cytoskeleton organization	0.034	0.016	-10000	0	-10000	0	0
IGF-1R heterotetramer	0.008	0.032	-10000	0	-0.5	2	2
GIT1	0.01	0	-10000	0	-10000	0	0
IGF1R	0.008	0.032	-10000	0	-0.5	2	2
IGF1	-0.002	0.076	-10000	0	-0.5	11	11
DIAPH1	-0.008	0.067	-10000	0	-0.56	7	7
Wnt receptor signaling pathway	0.001	0.015	0.24	2	-10000	0	2
RHOA	0.01	0	-10000	0	-10000	0	0
RhoA/GTP	-0.005	0.032	-10000	0	-0.39	1	1
CTNNA1	0.01	0	-10000	0	-10000	0	0
VCL	0.034	0.016	-10000	0	-10000	0	0
EFNA1	0.009	0.023	-10000	0	-0.5	1	1
LPP	0.034	0.019	-10000	0	-10000	0	0
Ephrin A1/EPHA2	-0.006	0.037	-10000	0	-0.45	1	1
SEC6/SEC8	-0.001	0.012	-10000	0	-10000	0	0
MGAT3	-0.11	0.13	-10000	0	-0.47	1	1
HGF/MET	-0.027	0.077	-10000	0	-0.46	4	4
HGF	-0.018	0.12	-10000	0	-0.5	27	27
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.024	0.016	-10000	0	-0.22	2	2
actin cable formation	0.06	0.031	-10000	0	-10000	0	0
KIAA1543	0.034	0.027	-10000	0	-0.45	1	1
KIFC3	0.029	0.02	-10000	0	-10000	0	0
NCK1	0.01	0	-10000	0	-10000	0	0
EXOC3	0.01	0	-10000	0	-10000	0	0
ACTN1	0.029	0.016	-10000	0	-10000	0	0
NCK1/GIT1	0	0	-10000	0	-10000	0	0
mol:GDP	-0.001	0.015	-10000	0	-0.24	2	2
EXOC4	0.01	0	-10000	0	-10000	0	0
STX4	0.029	0.016	-10000	0	-10000	0	0
PIP5K1C	0.029	0.016	-10000	0	-10000	0	0
LIMA1	0.01	0	-10000	0	-10000	0	0
ABI1	0.01	0	-10000	0	-10000	0	0
ROCK1	-0.004	0.028	-10000	0	-0.34	1	1
adherens junction assembly	0.045	0.038	-10000	0	-0.52	2	2
IGF-1R heterotetramer/IGF1	-0.007	0.037	-10000	0	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-10000	0	-10000	0	0
MET	-0.023	0.13	-10000	0	-0.51	31	31
PLEKHA7	0.029	0.016	-10000	0	-10000	0	0
mol:GTP	-0.006	0.038	-10000	0	-10000	0	0
establishment of epithelial cell apical/basal polarity	0.049	0.015	-10000	0	-10000	0	0
cortical actin cytoskeleton stabilization	0.024	0.016	-10000	0	-0.22	2	2
regulation of cell-cell adhesion	0.034	0.016	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.024	0.016	-10000	0	-0.22	2	2

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.01	0.069	-9999	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
CRKL	0.01	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	-0.013	0.045	-9999	-10000	0	0
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.004	0.021	-9999	-0.29	2	2
antigen processing and presentation of peptide antigen via MHC class I	-0.014	0.043	-9999	-0.33	3	3
CaM/Ca2+	-0.017	0.054	-9999	-10000	0	0
RAP1A	0.01	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	0.017	0.065	-9999	-10000	0	0
AKT1	0.026	0.06	-9999	-10000	0	0
MAP2K1	0.024	0.063	-9999	-10000	0	0
MAP3K11	0.016	0.066	-9999	-10000	0	0
IFNGR1	0.009	0.007	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.054	0.11	-9999	-0.37	46	46
Rap1/GTP	-0.012	0.04	-9999	-10000	0	0
CRKL/C3G	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.02	0.065	-9999	-10000	0	0
CEBPB	0.044	0.085	-9999	-0.42	9	9
STAT3	0.01	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.018	0.057	-9999	-10000	0	0
STAT1	0.017	0.065	-9999	-10000	0	0
CALM1	0.01	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.032	0.14	-9999	-0.51	40	40
PIK3CA	0.01	0	-9999	-10000	0	0
STAT1 (dimer)/PIAS1	0.022	0.062	-9999	-10000	0	0
CEBPB/PTGES2/Cbp/p300	-0.011	0.04	-9999	-0.35	2	2
mol:Ca2+	-0.018	0.059	-9999	-10000	0	0
MAPK3	0.033	0.062	-9999	-10000	0	0
STAT1 (dimer)	-0.017	0.058	-9999	-0.47	3	3
MAPK1	0.033	0.062	-9999	-10000	0	0
JAK2	0.007	0.033	-9999	-0.5	2	2
PIK3R1	0.009	0.023	-9999	-0.5	1	1
JAK1	0.009	0.007	-9999	-10000	0	0
CAMK2D	0.01	0	-9999	-10000	0	0
DAPK1	0.04	0.096	-9999	-0.6	9	9
SMAD7	0.028	0.041	-9999	-0.26	1	1
CBL/CRKL/C3G	-0.015	0.048	-9999	-10000	0	0
PI3K	-0.016	0.052	-9999	-10000	0	0
IFNG	-0.032	0.14	-9999	-0.51	40	40
apoptosis	0.029	0.073	-9999	-0.44	9	9
CAMK2G	0.01	0	-9999	-10000	0	0
STAT3 (dimer)	0.01	0	-9999	-10000	0	0
CAMK2A	-0.039	0.15	-9999	-0.5	47	47
CAMK2B	-0.082	0.2	-9999	-0.52	85	85
FRAP1	0.026	0.057	-9999	-10000	0	0
PRKCD	0.027	0.061	-9999	-10000	0	0
RAP1B	0.01	0	-9999	-10000	0	0
negative regulation of cell growth	-0.014	0.043	-9999	-0.33	3	3
PTPN2	0.01	0	-9999	-10000	0	0
EP300	0.01	0	-9999	-10000	0	0
IRF1	0.047	0.052	-9999	-10000	0	0
STAT1 (dimer)/PIASy	-0.015	0.052	-9999	-10000	0	0
SOCS1	0.002	0.016	-9999	-10000	0	0
mol:GDP	-0.014	0.047	-9999	-10000	0	0
CASP1	0.026	0.048	-9999	-0.3	5	5
PTGES2	0.01	0	-9999	-10000	0	0
IRF9	0.041	0.029	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.016	0.051	-9999	-10000	0	0
RAP1/GDP	-0.012	0.04	-9999	-10000	0	0
CBL	0.016	0.065	-9999	-10000	0	0
MAP3K1	0.017	0.066	-9999	-10000	0	0
PIAS1	0.01	0	-9999	-10000	0	0
PIAS4	0.01	0	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.014	0.043	-9999	-0.33	3	3
PTPN11	0.01	0.068	-9999	-10000	0	0
CREBBP	0.01	0	-9999	-10000	0	0
RAPGEF1	0.01	0	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	-0.011	0.055	-9999	-0.29	18	18
Ran/GTP/Exportin 1/HDAC1	0	0.01	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.026	0.059	-9999	-0.27	18	18
SUMO1	0.01	0	-9999	-10000	0	0
ZFPM1	0.009	0.024	-9999	-0.52	1	1
NPC/RanGAP1/SUMO1/Ubc9	0.017	0	-9999	-10000	0	0
FKBP3	0.009	0.024	-9999	-0.52	1	1
Histones	-0.005	0.025	-9999	-10000	0	0
YY1/LSF	0.024	0	-9999	-10000	0	0
SMG5	0.01	0	-9999	-10000	0	0
RAN	0.009	0.024	-9999	-0.52	1	1
I kappa B alpha/HDAC3	0.017	0.049	-9999	-10000	0	0
I kappa B alpha/HDAC1	0.019	0.035	-9999	-10000	0	0
SAP18	0.01	0	-9999	-10000	0	0
RELA	0.021	0.047	-9999	-0.22	18	18
HDAC1/Smad7	-0.001	0.013	-9999	-0.29	1	1
RANGAP1	0.01	0	-9999	-10000	0	0
HDAC3/TR2	0.019	0.035	-9999	-10000	0	0
NuRD/MBD3 Complex	0.037	0.012	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.024	0.043	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.033	0.14	-9999	-0.5	41	41
GATA1	-0.046	0.16	-9999	-0.5	52	52
Mad/Max	0	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.024	0.063	-9999	-0.28	1	1
RBBP7	0.01	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
RBBP4	0.01	0	-9999	-10000	0	0
MAX	0.01	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.01	0	-9999	-10000	0	0
NFKBIA	0.015	0.039	-9999	-10000	0	0
KAT2B	0.01	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.035	0	-9999	-10000	0	0
SIN3 complex	0	0	-9999	-10000	0	0
SMURF1	0.01	0	-9999	-10000	0	0
CHD3	0.01	0	-9999	-10000	0	0
SAP30	0.01	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.01	0	-9999	-10000	0	0
YY1/HDAC3	0.028	0.033	-9999	-10000	0	0
YY1/HDAC2	0.024	0	-9999	-10000	0	0
YY1/HDAC1	0.024	0	-9999	-10000	0	0
NuRD/MBD2 Complex (MeCP1)	0.038	0	-9999	-10000	0	0
PPARG	-0.046	0.12	-9999	-0.3	73	73
HDAC8/hEST1B	0	0	-9999	-10000	0	0
UBE2I	0.01	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.01	0	-9999	-10000	0	0
TNFRSF1A	0.01	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.019	0.035	-9999	-10000	0	0
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.001	0.013	-9999	-0.29	1	1
CREBBP	0.01	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.04	0.013	-9999	-10000	0	0
HDAC1	0.01	0	-9999	-10000	0	0
HDAC3	0.015	0.039	-9999	-10000	0	0
HDAC2	0.01	0	-9999	-10000	0	0
YY1	0.024	0	-9999	-10000	0	0
HDAC8	0.01	0	-9999	-10000	0	0
SMAD7	0.009	0.023	-9999	-0.5	1	1
NCOR2	0.01	0	-9999	-10000	0	0
MXD1	0.01	0	-9999	-10000	0	0
STAT3	0.02	0	-9999	-10000	0	0
NFKB1	0.01	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.01	0	-9999	-10000	0	0
YY1/LSF/HDAC1	0	0	-9999	-10000	0	0
YY1/SAP30/HDAC1	0	0	-9999	-10000	0	0
EP300	0.01	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.02	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.015	0.039	-9999	-10000	0	0
histone deacetylation	0.038	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.026	0.033	-9999	-10000	0	0
nuclear export	0	0	-9999	-10000	0	0
PRKACA	0.01	0	-9999	-10000	0	0
GATAD2B	0.01	0	-9999	-10000	0	0
GATAD2A	0.01	0	-9999	-10000	0	0
GATA2/HDAC3	-0.005	0.088	-9999	-0.27	41	41
GATA1/HDAC1	-0.037	0.11	-9999	-0.35	52	52
GATA1/HDAC3	-0.014	0.092	-9999	-0.26	52	52
CHD4	0.01	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.014	0.068	-9999	-0.35	19	19
SIN3/HDAC complex/Mad/Max	0.038	0	-9999	-10000	0	0
NuRD Complex	0.043	0.013	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.005	0.024	-9999	-10000	0	0
SIN3B	0.01	0	-9999	-10000	0	0
MTA2	0.01	0	-9999	-10000	0	0
SIN3A	0.01	0	-9999	-10000	0	0
XPO1	0.01	0	-9999	-10000	0	0
SUMO1/HDAC1	0.024	0	-9999	-10000	0	0
HDAC complex	0	0	-9999	-10000	0	0
GATA1/Fog1	-0.038	0.11	-9999	-0.36	52	52
FKBP25/HDAC1/HDAC2	-0.001	0.014	-9999	-0.3	1	1
TNF	-0.01	0.099	-9999	-0.5	19	19
negative regulation of cell growth	0.038	0	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.038	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0.01	-9999	-0.23	1	1
NF kappa B/RelA/I kappa B alpha	-0.011	0.055	-9999	-0.29	18	18
SIN3/HDAC complex/NCoR1	0.036	0	-9999	-10000	0	0
TFCP2	0.01	0	-9999	-10000	0	0
NR2C1	0.01	0	-9999	-10000	0	0
MBD3	0.008	0.032	-9999	-0.5	2	2
MBD2	0.01	0	-9999	-10000	0	0

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.047	0.037	-10000	0	-0.43	1	1
UGCG	-0.002	0.029	-10000	0	-0.62	1	1
AKT1/mTOR/p70S6K/Hsp90/TERT	0.04	0.056	-10000	0	-0.31	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.021	0.031	-10000	0	-0.61	1	1
mol:DAG	0	0.001	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.005	0.038	-10000	0	-0.34	5	5
FRAP1	0.064	0.059	-10000	0	-0.39	5	5
FOXO3	0.066	0.052	-10000	0	-0.35	4	4
AKT1	0.062	0.055	-10000	0	-0.38	4	4
GAB2	0.007	0.046	-10000	0	-0.5	4	4
SMPD1	-0.001	0.007	-10000	0	-10000	0	0
SGMS1	-0.001	0.007	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
mol:GDP	0.018	0.014	-10000	0	-0.29	1	1
CALM1	0.01	0	-10000	0	-10000	0	0
cell proliferation	0.039	0.033	-10000	0	-0.27	3	3
EIF3A	0.01	0	-10000	0	-10000	0	0
PI3K	0.019	0.017	-10000	0	-0.35	1	1
RPS6KB1	0.021	0.022	-10000	0	-10000	0	0
mol:sphingomyelin	0	0.001	-10000	0	-10000	0	0
natural killer cell activation	0.001	0.001	-10000	0	-0.011	2	2
JAK3	0.012	0.001	-10000	0	-10000	0	0
PIK3R1	0.012	0.023	-10000	0	-0.5	1	1
JAK1	0.012	0.001	-10000	0	-10000	0	0
NFKB1	0.01	0	-10000	0	-10000	0	0
MYC	0.062	0.076	-10000	0	-0.92	2	2
MYB	0.016	0.11	-10000	0	-1.2	4	4
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.055	0.05	-10000	0	-0.38	2	2
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.031	0.02	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.055	0.049	-10000	0	-0.37	2	2
Rac1/GDP	0.022	0.013	-10000	0	-0.26	1	1
T cell proliferation	0.057	0.052	-10000	0	-0.37	2	2
SHC1	0.01	0.024	-10000	0	-0.52	1	1
RAC1	0.01	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.004	0.007	-10000	0	-0.051	7	7
PRKCZ	0.057	0.053	-10000	0	-0.38	2	2
NF kappa B1 p50/RelA	-0.004	0.038	-10000	0	-0.37	3	3
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.043	0.04	-10000	0	-0.43	2	2
HSP90AA1	0.01	0	-10000	0	-10000	0	0
RELA	0.01	0	-10000	0	-10000	0	0
IL2RA	-0.027	0.14	-10000	0	-0.52	35	35
IL2RB	0.01	0.033	-10000	0	-0.5	2	2
TERT	-0.15	0.24	-10000	0	-0.52	146	146
E2F1	0.019	0.044	-10000	0	-0.42	4	4
SOS1	0.011	0.001	-10000	0	-10000	0	0
RPS6	0.01	0	-10000	0	-10000	0	0
mol:cAMP	-0.002	0.003	0.025	7	-10000	0	7
PTPN11	0.011	0.001	-10000	0	-10000	0	0
IL2RG	0.007	0.051	-10000	0	-0.5	5	5
actin cytoskeleton organization	0.057	0.052	-10000	0	-0.37	2	2
GRB2	0.011	0.001	-10000	0	-10000	0	0
IL2	0.009	0.005	-10000	0	-10000	0	0
PIK3CA	0.013	0.001	-10000	0	-10000	0	0
Rac1/GTP	0.028	0.013	-10000	0	-0.24	1	1
LCK	0.009	0.04	-10000	0	-0.5	3	3
BCL2	0.065	0.065	-10000	0	-0.65	2	2

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.002	0.021	-9999	-10000	0	0
DAPP1	-0.003	0.11	-9999	-0.48	17	17
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.002	0.15	-9999	-0.61	22	22
mol:DAG	0.023	0.068	-9999	-0.31	8	8
HRAS	0.011	0.001	-9999	-10000	0	0
RAP1A	0.01	0.001	-9999	-10000	0	0
ARF5/GDP	0.022	0.07	-9999	-0.44	8	8
PLCG2	0.007	0.04	-9999	-0.5	3	3
PLCG1	0.01	0	-9999	-10000	0	0
ARF5	0.01	0	-9999	-10000	0	0
mol:GTP	-0.002	0.018	-9999	-10000	0	0
ARF1/GTP	-0.002	0.019	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
YES1	0.01	0	-9999	-10000	0	0
RAP1A/GTP	-0.002	0.018	-9999	-10000	0	0
ADAP1	-0.002	0.024	-9999	-0.42	1	1
ARAP3	-0.002	0.018	-9999	-10000	0	0
INPPL1	0.01	0	-9999	-10000	0	0
PREX1	0.004	0.056	-9999	-0.5	6	6
ARHGEF6	-0.008	0.093	-9999	-0.5	17	17
ARHGEF7	0.01	0	-9999	-10000	0	0
ARF1	0.01	0	-9999	-10000	0	0
NRAS	0.011	0.001	-9999	-10000	0	0
FYN	0.009	0.023	-9999	-0.5	1	1
ARF6	0.01	0	-9999	-10000	0	0
FGR	-0.029	0.14	-9999	-0.5	37	37
mol:Ca2+	0.02	0.037	-9999	-10000	0	0
mol:IP4	0	0	-9999	-10000	0	0
TIAM1	0.002	0.065	-9999	-0.5	8	8
ZAP70	0.004	0.056	-9999	-0.5	6	6
mol:IP3	0.023	0.05	-9999	-0.21	6	6
LYN	0.01	0	-9999	-10000	0	0
ARF1/GDP	0.022	0.07	-9999	-0.44	8	8
RhoA/GDP	-0.006	0.035	-9999	-0.36	2	2
PDK1/Src/Hsp90	0	0	-9999	-10000	0	0
BLNK	0.008	0.032	-9999	-0.5	2	2
actin cytoskeleton reorganization	0.04	0.062	-9999	-0.46	4	4
SRC	0.01	0	-9999	-10000	0	0
PLEKHA2	0.021	0.028	-9999	-0.29	4	4
RAC1	0.01	0	-9999	-10000	0	0
PTEN	0	0.003	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
ARF6/GTP	-0.001	0.016	-9999	-10000	0	0
RhoA/GTP	-0.002	0.017	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.002	0.12	-9999	-0.49	17	17
BLK	-0.075	0.19	-9999	-0.52	79	79
PDPK1	0.01	0	-9999	-10000	0	0
CYTH1	-0.002	0.017	-9999	-10000	0	0
HCK	-0.012	0.1	-9999	-0.5	21	21
CYTH3	-0.002	0.022	-9999	-10000	0	0
CYTH2	-0.002	0.017	-9999	-10000	0	0
KRAS	0.01	0.024	-9999	-0.51	1	1
GO:0030676	0	0	-9999	-10000	0	0
FOXO3	-0.003	0.033	-9999	-0.49	2	2
SGK1	-0.003	0.036	-9999	-0.54	2	2
INPP5D	0.007	0.04	-9999	-0.5	3	3
mol:GDP	0.016	0.074	-9999	-0.44	9	9
SOS1	0.01	0	-9999	-10000	0	0
SYK	0.007	0.04	-9999	-0.5	3	3
ARF6/GDP	-0.006	0.035	-9999	-0.36	2	2
mol:PI-3-4-5-P3	-0.002	0.018	-9999	-10000	0	0
ARAP3/RAP1A/GTP	-0.002	0.018	-9999	-10000	0	0
VAV1	0.005	0.051	-9999	-0.5	5	5
mol:PI-3-4-P2	0.016	0.029	-9999	-0.35	3	3
RAS family/GTP/PI3K Class I	-0.002	0.018	-9999	-10000	0	0
PLEKHA1	0.022	0.024	-9999	-0.29	3	3
Rac1/GDP	0.022	0.07	-9999	-0.42	9	9
LAT	0.009	0.024	-9999	-0.52	1	1
Rac1/GTP	0.013	0.11	-9999	-0.46	19	19
ITK	-0.007	0.038	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.023	0.092	-9999	-0.35	18	18
LCK	0.007	0.04	-9999	-0.5	3	3
BTK	-0.016	0.06	-9999	-0.42	2	2

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	-0.021	0.076	-9999	-0.5	5	5
CLOCK	0.012	0.003	-9999	-10000	0	0
TIMELESS/CRY2	0.03	0.036	-9999	-10000	0	0
DEC1/BMAL1	0	0.001	-9999	-10000	0	0
ATR	0.01	0	-9999	-10000	0	0
NR1D1	0.032	0.021	-9999	-10000	0	0
ARNTL	0.012	0.003	-9999	-10000	0	0
TIMELESS	0.029	0.04	-9999	-10000	0	0
NPAS2	0.009	0.041	-9999	-0.51	3	3
CRY2	0.01	0	-9999	-10000	0	0
mol:CO	-0.01	0.009	-9999	-10000	0	0
CHEK1	-0.029	0.14	-9999	-0.52	36	36
mol:HEME	0.01	0.009	-9999	-10000	0	0
PER1	-0.012	0.1	-9999	-0.5	21	21
BMAL/CLOCK/NPAS2	0.031	0.027	-9999	-0.3	3	3
BMAL1/CLOCK	0.034	0.035	-9999	-10000	0	0
S phase of mitotic cell cycle	-0.021	0.076	-9999	-0.5	5	5
TIMELESS/CHEK1/ATR	-0.021	0.077	-9999	-0.51	5	5
mol:NADPH	0.01	0.009	-9999	-10000	0	0
PER1/TIMELESS	0.018	0.068	-9999	-0.52	1	1
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	0.002	0.004	-9999	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.031	0.011	-10000	0	-10000	0	0
regulation of axonogenesis	-0.023	0.003	-10000	0	-10000	0	0
myoblast fusion	-0.015	0.011	-10000	0	-10000	0	0
mol:GTP	0	0.003	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.007	0.1	0.29	53	-10000	0	53
ARF1/GTP	0	0.001	-10000	0	-10000	0	0
mol:GM1	0.009	0.003	-10000	0	-10000	0	0
mol:Choline	0.023	0.002	-10000	0	-10000	0	0
lamellipodium assembly	0.009	0.029	-10000	0	-10000	0	0
MAPK3	0.021	0.007	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.007	0.1	-10000	0	-0.29	53	53
ARF1	0.01	0	-10000	0	-10000	0	0
ARF6/GDP	0.015	0.011	-10000	0	-10000	0	0
ARF1/GDP	0.026	0.016	-10000	0	-10000	0	0
ARF6	0.01	0.002	-10000	0	-10000	0	0
RAB11A	0.01	0	-10000	0	-10000	0	0
TIAM1	0.003	0.065	-10000	0	-0.5	8	8
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.021	0.007	-10000	0	-10000	0	0
actin filament bundle formation	0	0.005	-10000	0	-10000	0	0
KALRN	0.005	0.029	-10000	0	-0.26	3	3
RAB11FIP3/RAB11A	0	0	-10000	0	-10000	0	0
RhoA/GDP	0	0.005	-10000	0	-10000	0	0
NME1	-0.039	0.16	-10000	0	-0.51	47	47
Rac1/GDP	0	0.005	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0	0.003	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	0.009	0.029	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
liver development	0	0.003	-10000	0	-10000	0	0
ARF6/GTP	0	0.003	-10000	0	-10000	0	0
RhoA/GTP	0	0.001	-10000	0	-10000	0	0
mol:GDP	0.008	0.024	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	0	0.001	-10000	0	-10000	0	0
RHOA	0.01	0	-10000	0	-10000	0	0
PLD1	0.017	0.003	-10000	0	-10000	0	0
RAB11FIP3	0.01	0	-10000	0	-10000	0	0
tube morphogenesis	0.009	0.029	-10000	0	-10000	0	0
ruffle organization	0.023	0.003	-10000	0	-10000	0	0
regulation of epithelial cell migration	0	0.003	-10000	0	-10000	0	0
PLD2	0.017	0.003	-10000	0	-10000	0	0
PIP5K1A	0.023	0.004	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.023	0.002	-10000	0	-10000	0	0
Rac1/GTP	0.009	0.029	-10000	0	-10000	0	0

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.006	0.046	-10000	0	-0.5	4	4
HRAS	0.01	0	-10000	0	-10000	0	0
EGFR	-0.005	0.086	-10000	0	-0.51	14	14
AKT	0.029	0.031	-10000	0	-0.34	3	3
FOXO3	0.01	0	-10000	0	-10000	0	0
AKT1	0.01	0	-10000	0	-10000	0	0
FOXO1	0.01	0	-10000	0	-10000	0	0
AKT3	0.007	0.04	-10000	0	-0.5	3	3
FOXO4	0.01	0	-10000	0	-10000	0	0
MET	-0.023	0.13	-10000	0	-0.51	31	31
PIK3CA	0.01	0	-10000	0	-10000	0	0
PIK3CB	0.01	0	-10000	0	-10000	0	0
NRAS	0.01	0	-10000	0	-10000	0	0
PIK3CG	-0.007	0.091	-10000	0	-0.5	16	16
PIK3R3	0.009	0.023	-10000	0	-0.5	1	1
PIK3R2	0.01	0	-10000	0	-10000	0	0
NF1	0.01	0	-10000	0	-10000	0	0
RAS	0.009	0.044	-10000	0	-0.24	4	4
ERBB2	0.007	0.041	-10000	0	-0.52	3	3
proliferation/survival/translation	-0.02	0.03	0.18	5	-10000	0	5
PI3K	0.014	0.05	-10000	0	-0.22	10	10
PIK3R1	0.009	0.023	-10000	0	-0.5	1	1
KRAS	0.009	0.024	-10000	0	-0.52	1	1
FOXO	0.037	0.014	-10000	0	-10000	0	0
AKT2	0.01	0	-10000	0	-10000	0	0
PTEN	0.01	0	-10000	0	-10000	0	0

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.009	0.023	-9999	-0.5	1	1
mol:S1P	0.001	0.002	-9999	-10000	0	0
S1P1/S1P/Gi	0.003	0.076	-9999	-0.23	43	43
GNAO1	0.005	0.058	-9999	-0.51	6	6
S1P/S1P3/G12/G13	-0.001	0.012	-9999	-0.27	1	1
AKT1	-0.008	0.035	-9999	-0.62	1	1
AKT3	0.023	0.1	-9999	-1.1	3	3
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.009	0.023	-9999	-0.5	1	1
GNAI2	0.011	0.002	-9999	-10000	0	0
GNAI3	0.011	0.002	-9999	-10000	0	0
GNAI1	0.009	0.033	-9999	-0.5	2	2
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.01	0.024	-9999	-0.52	1	1
S1PR2	0.01	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.013	0.072	-9999	-0.47	2	2
MAPK3	0.019	0.068	-9999	-0.45	2	2
MAPK1	0.019	0.068	-9999	-0.45	2	2
JAK2	0.021	0.069	-9999	-0.4	3	3
CXCR4	0.019	0.068	-9999	-0.45	2	2
FLT1	0.012	0.003	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.019	0.068	-9999	-0.45	2	2
S1P/S1P3/Gi	0.013	0.072	-9999	-0.48	2	2
RAC1	0.01	0	-9999	-10000	0	0
RhoA/GTP	-0.017	0.054	-9999	-0.43	2	2
VEGFA	0.012	0.003	-9999	-10000	0	0
S1P/S1P2/Gi	0.011	0.069	-9999	-0.41	2	2
VEGFR1 homodimer/VEGFA homodimer	0.021	0.005	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
S1P/S1P3/Gq	0.016	0.052	-9999	-0.25	16	16
GNAQ	0.009	0.023	-9999	-0.5	1	1
GNAZ	-0.032	0.14	-9999	-0.5	41	41
G12/G13	0	0	-9999	-10000	0	0
GNA14	-0.005	0.085	-9999	-0.5	14	14
GNA15	0.01	0	-9999	-10000	0	0
GNA12	0.01	0	-9999	-10000	0	0
GNA13	0.01	0	-9999	-10000	0	0
GNA11	0.008	0.032	-9999	-0.5	2	2
Rac1/GTP	-0.017	0.054	-9999	-0.43	2	2

×

TRAIL signaling pathway

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
TNFSF10	0.005	0.052	-10000	0	-0.5	5	5
positive regulation of NF-kappaB transcription factor activity	-0.005	0.046	-10000	0	-0.4	6	6
MAP2K4	0.035	0.027	-10000	0	-0.33	1	1
IKBKB	0.01	0	-10000	0	-10000	0	0
TNFRSF10B	0.01	0	-10000	0	-10000	0	0
TNFRSF10A	0.008	0.032	-10000	0	-0.5	2	2
SMPD1	-0.002	0.018	-10000	0	-0.19	4	4
IKBKG	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.008	0.032	-10000	0	-0.5	2	2
TRAIL/TRAILR2	-0.004	0.036	-10000	0	-0.36	5	5
TRAIL/TRAILR3	-0.008	0.061	-10000	0	-0.41	10	10
TRAIL/TRAILR1	-0.005	0.046	-10000	0	-0.4	6	6
TRAIL/TRAILR4	-0.005	0.046	-10000	0	-0.4	6	6
TRAIL/TRAILR1/DAP3/GTP	-0.004	0.036	-10000	0	-0.31	6	6
IKK complex	-0.001	0.013	-10000	0	-10000	0	0
RIPK1	0.01	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0	0	-10000	0	-10000	0	0
MAPK3	0.014	0.037	-10000	0	-0.35	5	5
MAP3K1	-0.003	0.025	-10000	0	-0.36	1	1
TRAILR4 (trimer)	0.008	0.032	-10000	0	-0.5	2	2
TRADD	0.01	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.008	0.032	-10000	0	-0.5	2	2
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.026	0.032	-10000	0	-0.46	1	1
CFLAR	0.01	0	-10000	0	-10000	0	0
MAPK1	0.014	0.037	-10000	0	-0.35	5	5
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.003	0.032	-10000	0	-0.49	1	1
mol:ceramide	-0.002	0.018	-10000	0	-0.19	4	4
FADD	0.01	0	-10000	0	-10000	0	0
MAPK8	0.04	0.025	-10000	0	-0.31	1	1
TRAF2	0.01	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.003	0.06	-10000	0	-0.5	7	7
CHUK	0.01	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.004	0.039	-10000	0	-0.34	6	6
DAP3	0.01	0	-10000	0	-10000	0	0
CASP10	-0.004	0.043	0.24	1	-0.36	5	6
JNK cascade	-0.005	0.046	-10000	0	-0.4	6	6
TRAIL (trimer)	0.005	0.052	-10000	0	-0.5	5	5
TNFRSF10C	0.003	0.06	-10000	0	-0.5	7	7
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.004	0.033	-10000	0	-0.28	6	6
TRAIL/TRAILR2/FADD	-0.003	0.03	-10000	0	-0.29	5	5
cell death	0.014	0.02	-10000	0	-0.19	4	4
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.027	0.024	-10000	0	-10000	0	0
TRAILR2 (trimer)	0.01	0	-10000	0	-10000	0	0
CASP8	-0.001	0.04	-10000	0	-0.86	1	1
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.002	0.024	-10000	0	-10000	0	0

×

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

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
BAG4	0.009	0.024	-9999	-0.52	1	1
Caspase 8 (4 units)	-0.006	0.038	-9999	-0.34	4	4
NEF	0.002	0.02	-9999	-10000	0	0
NFKBIA	0.011	0.011	-9999	-10000	0	0
BIRC3	0.029	0.057	-9999	-0.48	6	6
CYCS	0.036	0.043	-9999	-0.3	4	4
RIPK1	0.01	0	-9999	-10000	0	0
CD247	0.005	0.062	-9999	-0.52	6	6
MAP2K7	0.037	0.036	-9999	-0.33	1	1
protein ubiquitination	0.051	0.033	-9999	-10000	0	0
CRADD	0.009	0.024	-9999	-0.52	1	1
DAXX	0.01	0	-9999	-10000	0	0
FAS	0.006	0.046	-9999	-0.5	4	4
BID	0.031	0.045	-9999	-0.32	4	4
NF-kappa-B/RelA/I kappa B alpha	-0.003	0.027	-9999	-10000	0	0
TRADD	0.01	0	-9999	-10000	0	0
MAP3K5	0.01	0	-9999	-10000	0	0
CFLAR	0.01	0	-9999	-10000	0	0
FADD	0.01	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.003	0.027	-9999	-10000	0	0
MAPK8	0.042	0.035	-9999	-0.31	1	1
APAF1	0.01	0	-9999	-10000	0	0
TRAF1	0.01	0	-9999	-10000	0	0
TRAF2	0.01	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.026	0.047	-9999	-0.29	10	10
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.044	0.038	-9999	-10000	0	0
CHUK	0.052	0.034	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.002	0.029	-9999	-0.49	1	1
TCRz/NEF	-0.008	0.055	-9999	-0.34	12	12
TNF	-0.01	0.099	-9999	-0.5	19	19
FASLG	0.011	0.081	-9999	-0.47	12	12
NFKB1	0.011	0.011	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.012	0.058	-9999	-0.29	20	20
CASP6	-0.004	0.034	-9999	-0.59	1	1
CASP7	0.062	0.056	-9999	-0.47	3	3
RELA	0.011	0.011	-9999	-10000	0	0
CASP2	0.01	0	-9999	-10000	0	0
CASP3	0.062	0.056	-9999	-0.47	3	3
TNFRSF1A	0.01	0	-9999	-10000	0	0
TNFR1A/BAG4	-0.001	0.017	-9999	-0.37	1	1
CASP8	0.009	0.023	-9999	-0.5	1	1
CASP9	0.01	0	-9999	-10000	0	0
MAP3K14	0.048	0.036	-9999	-10000	0	0
APAF-1/Caspase 9	-0.007	0.041	-9999	-0.48	1	1
BCL2	0.044	0.041	-9999	-0.37	1	1

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.031	0.029	-9999	-0.42	2	2
KLHL20	-0.011	0.033	-9999	-0.25	2	2
CYFIP2	0.003	0.06	-9999	-0.5	7	7
Rac1/GDP	0.05	0.02	-9999	-10000	0	0
ENAH	0.031	0.029	-9999	-0.42	2	2
AP1M1	0.01	0	-9999	-10000	0	0
RAP1B	0.01	0	-9999	-10000	0	0
RAP1A	0.01	0	-9999	-10000	0	0
CTNNB1	0.01	0	-9999	-10000	0	0
CDC42/GTP	-0.001	0.01	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.009	0.024	-9999	-0.17	2	2
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.002	0.02	-9999	-0.26	3	3
RAPGEF1	0.041	0.025	-9999	-0.35	2	2
CTNND1	0.01	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.002	0.028	-9999	-0.43	2	2
CRK	0.037	0.027	-9999	-0.39	2	2
E-cadherin/gamma catenin/alpha catenin	-0.002	0.023	-9999	-0.3	3	3
alphaE/beta7 Integrin	-0.001	0.016	-9999	-0.35	1	1
IQGAP1	0.01	0	-9999	-10000	0	0
NCKAP1	0.01	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0	0	-9999	-10000	0	0
DLG1	0.032	0.029	-9999	-0.42	2	2
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.009	-9999	-10000	0	0
MLLT4	0.01	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.031	0.09	-9999	-0.28	53	53
PI3K	-0.001	0.011	-9999	-10000	0	0
ARF6	0.01	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.002	0.028	-9999	-0.36	3	3
TIAM1	0.002	0.065	-9999	-0.5	8	8
E-cadherin(dimer)/Ca2+	-0.001	0.015	-9999	-0.24	2	2
AKT1	-0.001	0.006	-9999	-10000	0	0
PIK3R1	0.009	0.023	-9999	-0.5	1	1
CDH1	0.008	0.032	-9999	-0.5	2	2
RhoA/GDP	0.05	0.02	-9999	-10000	0	0
actin cytoskeleton organization	-0.009	0.025	-9999	-0.18	2	2
CDC42/GDP	0.05	0.02	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.018	0.017	-9999	-0.23	2	2
ITGB7	0.009	0.023	-9999	-0.5	1	1
RAC1	0.01	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.001	0.016	-9999	-0.26	2	2
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.001	0.016	-9999	-0.25	2	2
mol:GDP	0.048	0.023	-9999	-0.28	2	2
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	0.009	0.024	-9999	-0.52	1	1
p120 catenin/RhoA/GDP	-0.001	0.015	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0	0	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
CDC42	0.01	0	-9999	-10000	0	0
CTNNA1	0.01	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.019	0.034	-9999	-0.21	6	6
NME1	-0.041	0.16	-9999	-0.52	47	47
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.031	0.029	-9999	-0.42	2	2
regulation of cell-cell adhesion	-0.001	0.009	-9999	-10000	0	0
WASF2	-0.004	0.012	-9999	-10000	0	0
Rap1/GTP	-0.001	0.012	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.002	0.021	-9999	-10000	0	0
CCND1	0.021	0.041	-9999	-0.26	6	6
VAV2	0.039	0.041	-9999	-0.46	3	3
RAP1/GDP	0	0.013	-9999	-10000	0	0
adherens junction assembly	0.032	0.028	-9999	-0.4	2	2
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.01	0	-9999	-10000	0	0
PIP5K1C	0.01	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.002	0.02	-9999	-10000	0	0
E-cadherin/beta catenin	-0.001	0.022	-9999	-0.34	2	2
mol:GTP	0	0	-9999	-10000	0	0
SRC	0.032	0.029	-9999	-0.42	2	2
PIK3CA	0.01	0	-9999	-10000	0	0
Rac1/GTP	-0.018	0.053	-9999	-0.42	2	2
E-cadherin/beta catenin/alpha catenin	-0.001	0.019	-9999	-0.29	2	2
ITGAE	0.01	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.002	0.028	-9999	-0.44	2	2

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.01	0	-10000	0	-10000	0	0
PTK2	0.01	0	-10000	0	-10000	0	0
CRKL	0.014	0.045	-10000	0	-0.46	1	1
GRB2/SOS1/SHC	-0.001	0.014	-10000	0	-0.3	1	1
HRAS	0.01	0	-10000	0	-10000	0	0
IRS1/Crk	0.014	0.045	-10000	0	-0.26	12	12
IGF-1R heterotetramer/IGF1/PTP1B	-0.007	0.045	-10000	0	-0.28	13	13
AKT1	0.03	0.04	-10000	0	-0.38	1	1
BAD	0.035	0.038	-10000	0	-0.36	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.014	0.045	-10000	0	-0.26	12	12
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.014	0.045	-10000	0	-0.46	1	1
RAF1	0.038	0.037	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.006	0.039	-10000	0	-0.43	1	1
YWHAZ	0.01	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.007	0.046	-10000	0	-0.28	12	12
PIK3CA	0.01	0	-10000	0	-10000	0	0
RPS6KB1	0.03	0.04	-10000	0	-0.38	1	1
GNB2L1	0.01	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	0.032	0.033	-10000	0	-10000	0	0
PXN	0.01	0	-10000	0	-10000	0	0
PIK3R1	0.009	0.023	-10000	0	-0.5	1	1
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
HRAS/GTP	-0.006	0.035	-10000	0	-0.39	1	1
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.006	0.035	-10000	0	-10000	0	0
IGF-1R heterotetramer	0.007	0.035	-10000	0	-0.51	2	2
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.007	0.042	-10000	0	-0.26	12	12
Crk/p130 Cas/Paxillin	-0.006	0.037	-10000	0	-0.41	1	1
IGF1R	0.007	0.035	-10000	0	-0.51	2	2
IGF1	-0.002	0.078	-10000	0	-0.51	11	11
IRS2/Crk	0.019	0.044	-10000	0	-0.43	1	1
PI3K	-0.007	0.04	-10000	0	-0.43	1	1
apoptosis	-0.037	0.035	0.31	1	-10000	0	1
HRAS/GDP	0	0	-10000	0	-10000	0	0
PRKCD	0.024	0.057	-10000	0	-0.34	10	10
RAF1/14-3-3 E	0.04	0.034	-10000	0	-10000	0	0
BAD/14-3-3	0.039	0.036	-10000	0	-0.32	1	1
PRKCZ	0.028	0.044	-10000	0	-0.38	1	1
Crk/p130 Cas/Paxillin/FAK1	-0.005	0.029	-10000	0	-0.32	1	1
PTPN1	0.01	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.019	0.06	-10000	0	-0.37	10	10
BCAR1	0.009	0.023	-10000	0	-0.5	1	1
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.007	0.04	-10000	0	-0.29	2	2
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.01	0	-10000	0	-10000	0	0
IRS1/NCK2	0.014	0.045	-10000	0	-0.26	12	12
GRB10	0.01	0	-10000	0	-10000	0	0
PTPN11	0.014	0.045	-10000	0	-0.46	1	1
IRS1	0.008	0.048	-10000	0	-0.28	12	12
IRS2	0.014	0.046	-10000	0	-0.36	2	2
IGF-1R heterotetramer/IGF1	-0.01	0.06	-10000	0	-0.37	13	13
GRB2	0.01	0	-10000	0	-10000	0	0
PDPK1	0.024	0.042	-10000	0	-0.4	1	1
YWHAE	0.01	0	-10000	0	-10000	0	0
PRKD1	0.014	0.079	-10000	0	-0.38	11	11
SHC1	0.009	0.024	-10000	0	-0.52	1	1

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.007	0.04	-10000	0	-0.25	13	13
MAPK9	0.007	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	0.001	0.03	-10000	0	-0.38	3	3
GNB1/GNG2	-0.001	0.019	-10000	0	-0.3	2	2
GNB1	0.01	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.007	0	-10000	0	-10000	0	0
Gs family/GTP	-0.006	0.042	-10000	0	-0.28	11	11
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	0.002	0.011	0.075	11	-10000	0	11
GNAL	-0.002	0.076	-10000	0	-0.5	11	11
GNG2	0.008	0.032	-10000	0	-0.5	2	2
CRH	0	0.041	-10000	0	-0.52	3	3
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.007	0	-10000	0	-10000	0	0
MAPK11	0.005	0.026	-10000	0	-0.32	3	3

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.003	0.034	-9999	-0.55	1	1
PDGFB-D/PDGFRB/SLAP	-0.009	0.061	-9999	-0.38	12	12
PDGFB-D/PDGFRB/APS/CBL	-0.001	0.019	-9999	-0.29	2	2
AKT1	0.044	0.032	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.024	0.042	-9999	-0.59	1	1
PIK3CA	0.01	0	-9999	-10000	0	0
FGR	-0.036	0.14	-9999	-0.51	37	37
mol:Ca2+	0.022	0.039	-9999	-0.63	1	1
MYC	0.032	0.071	-9999	-0.68	3	3
SHC1	0.009	0.024	-9999	-0.52	1	1
HRAS/GDP	0.002	0.013	-9999	-10000	0	0
LRP1/PDGFRB/PDGFB	-0.006	0.055	-9999	-0.39	8	8
GRB10	0.01	0	-9999	-10000	0	0
PTPN11	0.01	0	-9999	-10000	0	0
GO:0007205	0.022	0.039	-9999	-0.64	1	1
PTEN	0.01	0	-9999	-10000	0	0
GRB2	0.01	0	-9999	-10000	0	0
GRB7	0.004	0.057	-9999	-0.51	6	6
PDGFB-D/PDGFRB/SHP2	0	0.016	-9999	-0.36	1	1
PDGFB-D/PDGFRB/GRB10	0	0.016	-9999	-0.36	1	1
cell cycle arrest	-0.009	0.06	-9999	-0.38	12	12
HRAS	0.01	0	-9999	-10000	0	0
HIF1A	0.048	0.029	-9999	-10000	0	0
GAB1	0.02	0.05	-9999	-0.64	1	1
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.024	0.046	-9999	-0.57	1	1
PDGFB-D/PDGFRB	0.006	0.018	-9999	-0.31	1	1
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0	0.016	-9999	-0.36	1	1
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.004	0.035	-9999	-0.51	1	1
positive regulation of MAPKKK cascade	0	0.016	-9999	-0.35	1	1
PIK3R1	0.009	0.023	-9999	-0.5	1	1
mol:IP3	0.022	0.039	-9999	-0.65	1	1
E5	0	0.001	-9999	-10000	0	0
CSK	0.009	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.005	0.043	-9999	-0.36	7	7
SHB	0.009	0.023	-9999	-0.5	1	1
BLK	-0.016	0.054	-9999	-0.47	5	5
PTPN2	0.01	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0	0.016	-9999	-0.36	1	1
BCAR1	0.009	0.023	-9999	-0.5	1	1
VAV2	0.02	0.066	-9999	-0.55	2	2
CBL	0.01	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0	0.016	-9999	-0.36	1	1
LCK	0	0.037	-9999	-0.45	3	3
PDGFRB	0.01	0.023	-9999	-0.51	1	1
ACP1	0.01	0	-9999	-10000	0	0
HCK	-0.019	0.11	-9999	-0.53	21	21
ABL1	0.017	0.051	-9999	-0.6	1	1
PDGFB-D/PDGFRB/CBL	0.018	0.055	-9999	-0.73	1	1
PTPN1	0.01	0.001	-9999	-10000	0	0
SNX15	0.01	0	-9999	-10000	0	0
STAT3	0.01	0	-9999	-10000	0	0
STAT1	0.01	0	-9999	-10000	0	0
cell proliferation	0.032	0.064	-9999	-0.6	3	3
SLA	-0.003	0.079	-9999	-0.5	12	12
actin cytoskeleton reorganization	0.039	0.02	-9999	-10000	0	0
SRC	0.002	0.017	-9999	-0.34	1	1
PI3K	-0.004	0.028	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	-0.005	0.038	-9999	-0.3	8	8
SH2B2	0.009	0.023	-9999	-0.5	1	1
PLCgamma1/SPHK1	0.025	0.043	-9999	-0.62	1	1
LYN	0.003	0.017	-9999	-0.33	1	1
LRP1	0.006	0.046	-9999	-0.5	4	4
SOS1	0.01	0	-9999	-10000	0	0
STAT5B	0.01	0	-9999	-10000	0	0
STAT5A	0.009	0.023	-9999	-0.5	1	1
NCK1-2/p130 Cas	0.002	0.017	-9999	-10000	0	0
SPHK1	0.006	0.047	-9999	-0.51	4	4
EDG1	0.001	0.001	-9999	-10000	0	0
mol:DAG	0.022	0.039	-9999	-0.65	1	1
PLCG1	0.022	0.04	-9999	-0.67	1	1
NHERF/PDGFRB	-0.005	0.04	-9999	-0.3	9	9
YES1	0.002	0.017	-9999	-0.34	1	1
cell migration	-0.005	0.04	-9999	-0.29	9	9
SHC/Grb2/SOS1	0.002	0.018	-9999	-10000	0	0
SLC9A3R2	0.004	0.056	-9999	-0.5	6	6
SLC9A3R1	0.008	0.034	-9999	-0.52	2	2
NHERF1-2/PDGFRB/PTEN	-0.005	0.035	-9999	-0.27	2	2
FYN	0.002	0.029	-9999	-0.42	2	2
DOK1	0.026	0.013	-9999	-0.26	1	1
HRAS/GTP	0	0	-9999	-10000	0	0
PDGFB	0.004	0.056	-9999	-0.5	6	6
RAC1	0.029	0.066	-9999	-0.53	3	3
PRKCD	0.027	0.014	-9999	-0.27	1	1
FER	0.027	0.014	-9999	-0.27	1	1
MAPKKK cascade	-0.001	0.014	-9999	-10000	0	0
RASA1	0.027	0.014	-9999	-0.27	1	1
NCK1	0.01	0	-9999	-10000	0	0
NCK2	0.01	0	-9999	-10000	0	0
p62DOK/Csk	0.007	0.017	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHB	-0.001	0.023	-9999	-0.36	2	2
chemotaxis	0.017	0.05	-9999	-0.58	1	1
STAT1-3-5/STAT1-3-5	-0.001	0.014	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	-0.001	0.017	-9999	-0.37	1	1
PTPRJ	0.01	0	-9999	-10000	0	0

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.066	0.012	-9999	-10000	0	0
ERC1	0.01	0	-9999	-10000	0	0
RIP2/NOD2	-0.001	0.016	-9999	-0.35	1	1
NFKBIA	0.037	0	-9999	-10000	0	0
BIRC2	0.01	0	-9999	-10000	0	0
IKBKB	0.01	0	-9999	-10000	0	0
RIPK2	0.01	0	-9999	-10000	0	0
IKBKG	0	0.008	-9999	-10000	0	0
IKK complex/A20	-0.008	0.037	-9999	-10000	0	0
NEMO/A20/RIP2	0.01	0	-9999	-10000	0	0
XPO1	0.01	0	-9999	-10000	0	0
NEMO/ATM	0.04	0.009	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.009	0.024	-9999	-0.52	1	1
Exportin 1/RanGTP	-0.001	0.014	-9999	-0.31	1	1
IKK complex/ELKS	0	0.006	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0	0	-9999	-10000	0	0
NOD2	0.009	0.023	-9999	-0.5	1	1
NFKB1	0.013	0	-9999	-10000	0	0
RELA	0.013	0	-9999	-10000	0	0
MALT1	0.01	0	-9999	-10000	0	0
cIAP1/UbcH5C	0	0	-9999	-10000	0	0
ATM	0.01	0	-9999	-10000	0	0
TNF/TNFR1A	-0.014	0.068	-9999	-0.35	19	19
TRAF6	0.01	0	-9999	-10000	0	0
PRKCA	0.008	0.032	-9999	-0.5	2	2
CHUK	0.01	0	-9999	-10000	0	0
UBE2D3	0.01	0	-9999	-10000	0	0
TNF	-0.01	0.099	-9999	-0.5	19	19
NF kappa B1 p50/RelA	0	0	-9999	-10000	0	0
BCL10	0.01	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.037	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.013	0	-9999	-10000	0	0
TNFRSF1A	0.01	0	-9999	-10000	0	0
IKK complex	0	0.007	-9999	-10000	0	0
CYLD	0.01	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.001	0.014	-9999	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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
ITGB1	0.01	0	-9999	-10000	0	0
ITGB7	0.009	0.023	-9999	-0.5	1	1
ITGA4	0.008	0.032	-9999	-0.5	2	2
alpha4/beta7 Integrin	-0.002	0.027	-9999	-0.35	3	3
alpha4/beta1 Integrin	-0.001	0.022	-9999	-0.35	2	2

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.06	0.032	-10000	0	-10000	0	0
CRKL	0.035	0.034	-10000	0	-0.43	1	1
mol:DAG	0.04	0.027	-10000	0	-0.31	1	1
HRAS	0.05	0.039	-10000	0	-0.54	1	1
MAPK8	0.027	0.026	-10000	0	-0.28	1	1
RAP1A	0.035	0.034	-10000	0	-0.43	1	1
GAB1	0.033	0.044	-10000	0	-0.67	1	1
MAPK14	0.027	0.026	-10000	0	-0.28	1	1
EPO	0.005	0.048	-10000	0	-0.52	4	4
PLCG1	0.04	0.027	-10000	0	-0.32	1	1
EPOR/TRPC2/IP3 Receptors	0.012	0.004	-10000	0	-10000	0	0
RAPGEF1	0.01	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.005	0.038	-10000	0	-0.3	8	8
GAB1/SHC/GRB2/SOS1	-0.004	0.035	-10000	0	-0.58	1	1
EPO/EPOR (dimer)	0.014	0.035	-10000	0	-0.37	4	4
IRS2	0.034	0.039	-10000	0	-0.43	2	2
STAT1	0.048	0.03	-10000	0	-10000	0	0
STAT5B	0.044	0.029	-10000	0	-10000	0	0
cell proliferation	0.032	0.024	-10000	0	-10000	0	0
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.006	0.038	-10000	0	-0.46	2	2
TEC	0.035	0.034	-10000	0	-0.43	1	1
SOCS3	0.006	0.046	-10000	0	-0.5	4	4
STAT1 (dimer)	0.047	0.029	-10000	0	-10000	0	0
JAK2	0.009	0.034	-10000	0	-0.51	2	2
PIK3R1	0.009	0.023	-10000	0	-0.5	1	1
EPO/EPOR (dimer)/JAK2	0.039	0.037	-10000	0	-0.46	1	1
EPO/EPOR	0.014	0.035	-10000	0	-0.37	4	4
LYN	0.011	0.001	-10000	0	-10000	0	0
TEC/VAV2	0.04	0.035	-10000	0	-0.42	1	1
elevation of cytosolic calcium ion concentration	0.012	0.004	-10000	0	-10000	0	0
SHC1	0.009	0.024	-10000	0	-0.52	1	1
EPO/EPOR (dimer)/LYN	0.025	0.029	-10000	0	-0.29	4	4
mol:IP3	0.04	0.027	-10000	0	-0.31	1	1
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.005	0.037	-10000	0	-0.4	3	3
SH2B3	0.009	0.033	-10000	0	-0.5	2	2
NFKB1	0.027	0.026	-10000	0	-0.28	1	1
EPO/EPOR (dimer)/JAK2/SOCS3	-0.003	0.035	0.24	2	-0.35	2	4
PTPN6	0.029	0.035	-10000	0	-0.46	1	1
TEC/VAV2/GRB2	0.043	0.034	-10000	0	-0.4	1	1
EPOR	0.012	0.004	-10000	0	-10000	0	0
INPP5D	0.007	0.04	-10000	0	-0.5	3	3
mol:GDP	-0.004	0.035	-10000	0	-0.59	1	1
SOS1	0.01	0	-10000	0	-10000	0	0
PLCG2	0.007	0.04	-10000	0	-0.5	3	3
CRKL/CBL/C3G	0.044	0.032	-10000	0	-0.4	1	1
VAV2	0.034	0.036	-10000	0	-0.43	1	1
CBL	0.035	0.034	-10000	0	-0.43	1	1
SHC/Grb2/SOS1	-0.003	0.028	-10000	0	-0.4	1	1
STAT5A	0.043	0.037	-10000	0	-0.49	1	1
GRB2	0.01	0	-10000	0	-10000	0	0
STAT5 (dimer)	0.057	0.04	-10000	0	-0.44	1	1
LYN/PLCgamma2	-0.002	0.027	-10000	0	-0.35	3	3
PTPN11	0.01	0	-10000	0	-10000	0	0
BTK	0.018	0.079	-10000	0	-0.46	5	5
BCL2	0.058	0.052	-10000	0	-0.81	1	1

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.023	0.026	-9999	-0.31	3	3
CRKL	0.01	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0.01	0	-9999	-10000	0	0
ITGA4	0.008	0.032	-9999	-0.5	2	2
alpha4/beta7 Integrin/MAdCAM1	-0.005	0.036	-9999	-0.27	6	6
EPO	0.002	0.047	-9999	-0.52	4	4
alpha4/beta7 Integrin	-0.002	0.027	-9999	-0.35	3	3
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.001	0.022	-9999	-0.35	2	2
EPO/EPOR (dimer)	-0.003	0.033	-9999	-0.37	4	4
lamellipodium assembly	0	0.012	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
PI3K	-0.001	0.016	-9999	-0.35	1	1
ARF6	0.01	0	-9999	-10000	0	0
JAK2	0.021	0.037	-9999	-0.44	2	2
PXN	0.01	0	-9999	-10000	0	0
PIK3R1	0.009	0.023	-9999	-0.5	1	1
MADCAM1	0.002	0.058	-9999	-0.52	6	6
cell adhesion	-0.005	0.036	-9999	-0.27	6	6
CRKL/CBL	0	0	-9999	-10000	0	0
ITGB1	0.01	0	-9999	-10000	0	0
SRC	0.023	0.031	-9999	-0.26	6	6
ITGB7	0.009	0.023	-9999	-0.5	1	1
RAC1	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.004	0.032	-9999	-0.29	6	6
p130Cas/Crk/Dock1	0.037	0.029	-9999	-10000	0	0
VCAM1	0.006	0.046	-9999	-0.5	4	4
RHOA	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.001	0.016	-9999	-0.26	2	2
BCAR1	0.028	0.032	-9999	-10000	0	0
EPOR	0.01	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.01	0	-9999	-10000	0	0
GIT1	0.01	0	-9999	-10000	0	0
Rac1/GTP	0	0.012	-9999	-10000	0	0

×

ceramide signaling pathway

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
MAP4K4	0.034	0.041	-10000	0	-10000	0	0
BAG4	0.009	0.024	-10000	0	-0.52	1	1
BAD	0.024	0.018	-10000	0	-10000	0	0
NFKBIA	0.01	0	-10000	0	-10000	0	0
BIRC3	0.003	0.057	-10000	0	-0.51	6	6
BAX	0.024	0.018	-10000	0	-10000	0	0
EnzymeConsortium:3.1.4.12	0.011	0.013	-10000	0	-10000	0	0
IKBKB	0.038	0.04	-10000	0	-10000	0	0
MAP2K2	0.033	0.02	-10000	0	-10000	0	0
MAP2K1	0.033	0.02	-10000	0	-10000	0	0
SMPD1	0.015	0.013	-10000	0	-10000	0	0
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.038	0.043	-10000	0	-0.29	1	1
MAP2K4	0.029	0.018	-10000	0	-10000	0	0
protein ubiquitination	0.04	0.04	-10000	0	-10000	0	0
EnzymeConsortium:2.7.1.37	0.037	0.023	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.029	0.02	-10000	0	-10000	0	0
CRADD	0.009	0.024	-10000	0	-0.52	1	1
mol:ceramide	0.019	0.018	-10000	0	-10000	0	0
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-10000	0	-10000	0	0
MADD	0.01	0	-10000	0	-10000	0	0
MAP3K1	0.024	0.018	-10000	0	-10000	0	0
TRADD	0.01	0	-10000	0	-10000	0	0
RELA/p50	0.01	0	-10000	0	-10000	0	0
MAPK3	0.035	0.02	-10000	0	-10000	0	0
MAPK1	0.035	0.02	-10000	0	-10000	0	0
p50/RELA/I-kappa-B-alpha	0	0	-10000	0	-10000	0	0
FADD	0.034	0.041	-10000	0	-10000	0	0
KSR1	0.024	0.019	-10000	0	-10000	0	0
MAPK8	0.033	0.017	-10000	0	-10000	0	0
TRAF2	0.01	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	0.038	0.04	-10000	0	-10000	0	0
TNF R/SODD	-0.001	0.017	-10000	0	-0.37	1	1
TNF	-0.01	0.099	-10000	0	-0.5	19	19
CYCS	0.025	0.018	0.13	1	-10000	0	1
IKBKG	0.038	0.04	-10000	0	-10000	0	0
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.029	0.043	-10000	0	-10000	0	0
RELA	0.01	0	-10000	0	-10000	0	0
RIPK1	0.01	0	-10000	0	-10000	0	0
AIFM1	0.025	0.018	0.13	1	-10000	0	1
TNF/TNF R/SODD	-0.012	0.058	-10000	0	-0.29	20	20
TNFRSF1A	0.01	0	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.021	0.034	-10000	0	-0.68	1	1
NSMAF	0.033	0.041	-10000	0	-10000	0	0
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
BCL2	0.007	0.041	-10000	0	-0.51	3	3

×

E-cadherin signaling 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.002	0.023	-9999	-0.3	3	3
E-cadherin/beta catenin	-0.001	0.022	-9999	-0.35	2	2
CTNNB1	0.01	0	-9999	-10000	0	0
JUP	0.009	0.024	-9999	-0.52	1	1
CDH1	0.008	0.032	-9999	-0.5	2	2

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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
SMAD4	0.01	0	-9999	-10000	0	0
SMAD2	0.011	0	-9999	-10000	0	0
SMAD3	0.033	0	-9999	-10000	0	0
SMAD3/SMAD4	0.036	0.008	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	0	0	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	-0.003	0.027	-9999	-10000	0	0
PPM1A	0.01	0	-9999	-10000	0	0
CALM1	0.01	0	-9999	-10000	0	0
SMAD2/SMAD4	0.016	0	-9999	-10000	0	0
MAP3K1	0.01	0	-9999	-10000	0	0
TRAP-1/SMAD4	-0.001	0.022	-9999	-0.35	2	2
MAPK3	0.01	0	-9999	-10000	0	0
MAPK1	0.01	0	-9999	-10000	0	0
NUP214	0.01	0	-9999	-10000	0	0
CTDSP1	0.01	0	-9999	-10000	0	0
CTDSP2	0.01	0	-9999	-10000	0	0
CTDSPL	0.01	0	-9999	-10000	0	0
KPNB1	0.01	0	-9999	-10000	0	0
TGFBRAP1	0.008	0.032	-9999	-0.5	2	2
UBE2I	0.01	0	-9999	-10000	0	0
NUP153	0.01	0	-9999	-10000	0	0
KPNA2	0.002	0.063	-9999	-0.52	7	7
PIAS4	0.01	0	-9999	-10000	0	0

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.003	0.028	-10000	0	-0.29	3	3
CaM/Ca2+	0	0	-10000	0	-10000	0	0
AKT1	0.01	0	-10000	0	-10000	0	0
AKT2	0.01	0	-10000	0	-10000	0	0
STXBP4	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.032	0.037	0.21	1	-0.32	3	4
YWHAZ	0.01	0	-10000	0	-10000	0	0
CALM1	0.01	0	-10000	0	-10000	0	0
YWHAQ	0.01	0	-10000	0	-10000	0	0
TBC1D4	0.018	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.01	0	-10000	0	-10000	0	0
YWHAB	0.01	0	-10000	0	-10000	0	0
SNARE/Synip	0	0	-10000	0	-10000	0	0
YWHAG	0.01	0	-10000	0	-10000	0	0
ASIP	0.005	0.024	-10000	0	-0.52	1	1
PRKCI	0.01	0	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0	0	-10000	0	-10000	0	0
RHOQ	0.01	0	-10000	0	-10000	0	0
GYS1	0.025	0	-10000	0	-10000	0	0
PRKCZ	0.007	0.04	-10000	0	-0.5	3	3
TRIP10	0.01	0	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-10000	0	-10000	0	0
AS160/14-3-3	0.035	0.018	-10000	0	-10000	0	0
VAMP2	0.01	0	-10000	0	-10000	0	0
SLC2A4	0.032	0.04	0.21	1	-0.36	3	4
STX4	0.01	0	-10000	0	-10000	0	0
GSK3B	0.02	0	-10000	0	-10000	0	0
SFN	0	0.071	-10000	0	-0.52	9	9
LNPEP	0.01	0	-10000	0	-10000	0	0
YWHAE	0.01	0	-10000	0	-10000	0	0

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.01	0	-10000	0	-10000	0	0
mol:PIP3	-0.001	0.016	-10000	0	-0.25	2	2
FRAP1	0.012	0.005	-10000	0	-10000	0	0
AKT1	0.022	0.015	-10000	0	-10000	0	0
INSR	0.01	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.011	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0	0.004	-10000	0	-10000	0	0
TSC2	0.01	0	-10000	0	-10000	0	0
RHEB/GDP	-0.001	0.013	-10000	0	-10000	0	0
TSC1	0.01	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.012	0.015	-10000	0	-0.32	1	1
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0	0.005	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.01	0	-10000	0	-10000	0	0
RPS6KB1	0.022	0.01	-10000	0	-10000	0	0
MAP3K5	0.008	0	-10000	0	-10000	0	0
PIK3R1	0.009	0.023	-10000	0	-0.5	1	1
apoptosis	0.008	0	-10000	0	-10000	0	0
mol:LY294002	0	0	-10000	0	-0.001	1	1
EIF4B	0.026	0.009	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0	0.006	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	0	0.002	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.018	0.018	-10000	0	-0.26	2	2
mTOR/RHEB/GTP/Raptor/GBL	0.025	0.009	-10000	0	-10000	0	0
FKBP1A	0.01	0	-10000	0	-10000	0	0
RHEB/GTP	-0.001	0.013	-10000	0	-10000	0	0
mol:Amino Acids	0	0	-10000	0	-0.001	1	1
FKBP12/Rapamycin	0	0	-10000	0	-10000	0	0
PDPK1	-0.001	0.015	-10000	0	-0.24	1	1
EIF4E	0.01	0	-10000	0	-10000	0	0
ASK1/PP5C	0.017	0.003	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.013	0.006	-10000	0	-10000	0	0
TSC1/TSC2	-0.001	0.012	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	0.001	1	-10000	0	1
RPS6	0.01	0	-10000	0	-10000	0	0
PPP5C	0.01	0	-10000	0	-10000	0	0
EIF4G1	0.01	0	-10000	0	-10000	0	0
IRS1	0.006	0.016	-10000	0	-0.35	1	1
INS	0	0	-10000	0	-10000	0	0
PTEN	0.01	0	-10000	0	-10000	0	0
PDK2	-0.001	0.015	-10000	0	-0.24	1	1
EIF4EBP1	0.007	0.012	-10000	0	-10000	0	0
PIK3CA	0.01	0	-10000	0	-10000	0	0
PPP2R5D	0.017	0.005	-10000	0	-10000	0	0
peptide biosynthetic process	0.014	0	-10000	0	-10000	0	0
RHEB	0.009	0.024	-10000	0	-0.52	1	1
EIF4A1	0.01	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	-10000	0	-10000	0	0
EEF2	0.014	0	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.012	0.011	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	0.018	0	-9999	-10000	0	0
BAD/BCL-XL/YWHAZ	0	0	-9999	-10000	0	0
CDKN1B	0.03	0	-9999	-10000	0	0
CDKN1A	0.029	0.011	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
PRKDC	0.01	0	-9999	-10000	0	0
FOXO3	0.03	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
BAD	0.01	0	-9999	-10000	0	0
AKT3	0.012	0.026	-9999	-0.31	3	3
mol:GTP	0	0	-9999	-10000	0	0
FOXO4	0.03	0	-9999	-10000	0	0
AKT1/ASK1	0	0	-9999	-10000	0	0
BAD/YWHAZ	0	0	-9999	-10000	0	0
RICTOR	0.01	0	-9999	-10000	0	0
RAF1	0.01	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
TSC1	0.03	0	-9999	-10000	0	0
YWHAZ	0.01	0	-9999	-10000	0	0
AKT1/RAF1	0.029	0	-9999	-10000	0	0
EP300	0.01	0	-9999	-10000	0	0
mol:GDP	0.024	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
TSC2	0.03	0	-9999	-10000	0	0
YWHAQ	0.01	0	-9999	-10000	0	0
TBC1D4	0.019	0	-9999	-10000	0	0
MAP3K5	0.01	0	-9999	-10000	0	0
MAPKAP1	0.01	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.034	0.012	-9999	-10000	0	0
YWHAH	0.01	0	-9999	-10000	0	0
AKT1S1	0.03	0	-9999	-10000	0	0
CASP9	0.03	0	-9999	-10000	0	0
YWHAB	0.01	0	-9999	-10000	0	0
p27Kip1/KPNA1	0.034	0	-9999	-10000	0	0
GBL	0	0	-9999	-10000	0	0
PDK1/Src/Hsp90	0	0	-9999	-10000	0	0
YWHAE	0.01	0	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
AKT2/p21CIP1	0	0.01	-9999	-10000	0	0
KIAA1303	0	0	-9999	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.014	0.003	-9999	-10000	0	0
CHUK	0.03	0	-9999	-10000	0	0
BAD/BCL-XL	0.039	0	-9999	-10000	0	0
mTORC2	0	0	-9999	-10000	0	0
AKT2	0.014	0	-9999	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.046	0.012	-9999	-10000	0	0
PDPK1	0.01	0	-9999	-10000	0	0
MDM2	0.029	0.017	-9999	-10000	0	0
MAPKKK cascade	-0.029	0	-9999	-10000	0	0
MDM2/Cbp/p300	0.038	0.016	-9999	-10000	0	0
TSC1/TSC2	0.035	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.001	0.013	-9999	-10000	0	0
glucose import	0.021	0.031	-9999	-0.26	6	6
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.025	0.003	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	0.021	0.031	-9999	-0.26	6	6
GSK3A	0.03	0	-9999	-10000	0	0
FOXO1	0.03	0	-9999	-10000	0	0
GSK3B	0.03	0	-9999	-10000	0	0
SFN	0	0.071	-9999	-0.52	9	9
G1/S transition of mitotic cell cycle	0.035	0	-9999	-10000	0	0
p27Kip1/14-3-3 family	0.036	0.017	-9999	-10000	0	0
PRKACA	0.01	0	-9999	-10000	0	0
KPNA1	0.01	0	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
YWHAG	0.01	0	-9999	-10000	0	0
RHEB	0.009	0.024	-9999	-0.52	1	1
CREBBP	0.01	0	-9999	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.01	0	-9999	-10000	0	0
Rac1/GDP	0	0.003	-9999	-10000	0	0
DOCK1	0.01	0	-9999	-10000	0	0
ITGA4	0.008	0.032	-9999	-0.5	2	2
RAC1	0.01	0	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.002	0.027	-9999	-0.35	3	3
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.001	0.019	-9999	-0.29	2	2
alpha4/beta7 Integrin/Paxillin	-0.002	0.02	-9999	-10000	0	0
lamellipodium assembly	-0.001	0.019	-9999	-0.34	1	1
PIK3CA	0.01	0	-9999	-10000	0	0
PI3K	-0.001	0.016	-9999	-0.35	1	1
ARF6	0.01	0	-9999	-10000	0	0
TLN1	0.009	0.023	-9999	-0.5	1	1
PXN	0.018	0	-9999	-10000	0	0
PIK3R1	0.009	0.023	-9999	-0.5	1	1
ARF6/GTP	-0.001	0.013	-9999	-10000	0	0
cell adhesion	-0.001	0.018	-9999	-10000	0	0
CRKL/CBL	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	-0.001	0.016	-9999	-0.26	2	2
ITGB1	0.01	0	-9999	-10000	0	0
ITGB7	0.009	0.023	-9999	-0.5	1	1
ARF6/GDP	0	0.003	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.003	0.026	-9999	-10000	0	0
p130Cas/Crk/Dock1	-0.001	0.013	-9999	-0.29	1	1
VCAM1	0.006	0.046	-9999	-0.5	4	4
alpha4/beta1 Integrin/Paxillin/Talin	-0.001	0.018	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.001	0.015	-9999	-10000	0	0
BCAR1	0.009	0.023	-9999	-0.5	1	1
mol:GDP	0.001	0.015	-9999	-10000	0	0
CBL	0.01	0	-9999	-10000	0	0
PRKACA	0.01	0	-9999	-10000	0	0
GIT1	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.001	0.018	-9999	-10000	0	0
Rac1/GTP	-0.001	0.021	-9999	-0.38	1	1

×

Atypical NF-kappaB 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
BCL3/RelA	-0.001	0.016	-9999	-0.35	1	1
FBXW11	0.01	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.021	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.036	0.02	-9999	-10000	0	0
NFKBIA	0.021	0.023	-9999	-0.2	5	5
MAPK14	0.01	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.021	0	-9999	-10000	0	0
ARRB2	0.014	0	-9999	-10000	0	0
REL	0.01	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.02	0.014	-9999	-0.29	1	1
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.021	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
NF kappa B1 p50 dimer	0.016	0	-9999	-10000	0	0
PIK3R1	0.009	0.023	-9999	-0.5	1	1
NFKB1	0.018	0	-9999	-10000	0	0
RELA	0.01	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.026	0.022	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.038	0.02	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
PI3K	-0.001	0.016	-9999	-0.35	1	1
NF kappa B1 p50/RelA	0.026	0.023	-9999	-10000	0	0
IKBKB	0.01	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.01	0	-9999	-10000	0	0
SYK	0.007	0.04	-9999	-0.5	3	3
I kappa B alpha/PIK3R1	0.025	0.024	-9999	-0.23	1	1
cell death	-0.002	0.015	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	0.021	0	-9999	-10000	0	0
LCK	0.007	0.04	-9999	-0.5	3	3
BCL3	0.009	0.023	-9999	-0.5	1	1

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.01	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.001	0.013	-9999	-10000	0	0
MDM2/SUMO1	0.022	0.017	-9999	-0.24	2	2
HDAC4	0.009	0.024	-9999	-0.52	1	1
Ran/GTP/Exportin 1/HDAC1	0	0.009	-9999	-10000	0	0
SUMO1	0.01	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.014	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.023	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.009	0.024	-9999	-0.52	1	1
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.01	0	-9999	-10000	0	0
SUMO1/HDAC4	0.023	0.012	-9999	-0.24	1	1
SUMO1/HDAC1	0.024	0	-9999	-10000	0	0
RANGAP1	0.01	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	-0.001	0.017	-9999	-0.27	2	2
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.017	0	-9999	-10000	0	0
Ran/GTP	0	0.011	-9999	-0.24	1	1
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.008	0.034	-9999	-0.52	2	2
UBE2I	0.01	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0.01	-9999	-0.23	1	1
NPC	0	0	-9999	-10000	0	0
PIAS2	0.01	0	-9999	-10000	0	0
PIAS1	0.01	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0.039	0.017	-9999	-10000	0	0
adherens junction organization	0.032	0.025	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
Rac1/GDP	0.036	0.043	-9999	-10000	0	0
FMN1	0.025	0.049	-9999	-10000	0	0
mol:IP3	-0.001	0.012	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.029	0.018	-9999	-0.23	2	2
CTNNB1	0.01	0.001	-9999	-10000	0	0
AKT1	0.037	0.016	-9999	-10000	0	0
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.029	0.028	-9999	-0.36	2	2
CTNND1	0.011	0.001	-9999	-10000	0	0
mol:PI-4-5-P2	0.034	0.017	-9999	-10000	0	0
VASP	0.034	0.017	-9999	-10000	0	0
ZYX	0.033	0.021	-9999	-10000	0	0
JUB	0.033	0.024	-9999	-10000	0	0
EGFR(dimer)	0.026	0.047	-9999	-0.32	1	1
E-cadherin/beta catenin-gamma catenin	-0.002	0.022	-9999	-0.29	3	3
mol:PI-3-4-5-P3	-0.001	0.014	-9999	-10000	0	0
PIK3CA	0.011	0.001	-9999	-10000	0	0
PI3K	-0.001	0.014	-9999	-10000	0	0
FYN	0.02	0.064	-9999	-10000	0	0
mol:Ca2+	0.032	0.015	-9999	-10000	0	0
JUP	0.009	0.024	-9999	-0.52	1	1
PIK3R1	0.01	0.023	-9999	-0.5	1	1
mol:DAG	-0.001	0.012	-9999	-10000	0	0
CDH1	0.008	0.032	-9999	-0.5	2	2
RhoA/GDP	0.036	0.043	-9999	-10000	0	0
establishment of polarity of embryonic epithelium	0.034	0.017	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
RAC1	0.01	0	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
EGFR	-0.005	0.086	-9999	-0.51	14	14
CASR	0.01	0.078	-9999	-10000	0	0
RhoA/GTP	-0.001	0.011	-9999	-10000	0	0
AKT2	0.037	0.016	-9999	-10000	0	0
actin cable formation	0.03	0.048	-9999	-10000	0	0
apoptosis	0.001	0.013	-9999	-10000	0	0
CTNNA1	0.011	0.001	-9999	-10000	0	0
mol:GDP	0.032	0.045	-9999	-0.29	1	1
PIP5K1A	0.034	0.017	-9999	-10000	0	0
PLCG1	-0.001	0.013	-9999	-10000	0	0
Rac1/GTP	-0.007	0.037	-9999	-0.3	1	1
homophilic cell adhesion	0.001	0.001	-9999	-10000	0	0

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0	0	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.016	0	-9999	-10000	0	0
AP2	0	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0	-9999	-10000	0	0
CLTB	0.01	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.02	0	-9999	-10000	0	0
CD4	0	0.072	-9999	-0.5	10	10
CLTA	0.01	0	-9999	-10000	0	0
mol:GTP	0.001	0	-9999	-10000	0	0
ARFGAP1	0.009	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
ARF1/GTP	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.022	0	-9999	-10000	0	0
mol:Choline	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.01	0	-9999	-10000	0	0
DDEF1	0	0	-9999	-10000	0	0
ARF1/GDP	0	0	-9999	-10000	0	0
AP2M1	0.01	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0	0	-9999	-10000	0	0
Rac/GTP	0	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0	0	-9999	-10000	0	0
ARFIP2	0	0	-9999	-10000	0	0
COPA	0.01	0	-9999	-10000	0	0
RAC1	0.01	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.02	0	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0	-9999	-10000	0	0
GGA3	0.01	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0	0	-9999	-10000	0	0
AP2A1	0.01	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.022	0	-9999	-10000	0	0
ARF1/GDP/Membrin	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0	0	-9999	-10000	0	0
CYTH2	0.01	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0	0	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0	0	-9999	-10000	0	0
mol:Brefeldin A	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.024	0.031	-9999	-0.19	10	10
PLD2	0	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.009	0	-9999	-10000	0	0
PIP5K1A	0	0	-9999	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0	0	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	0.009	0	-9999	-10000	0	0
GOSR2	0	0	-9999	-10000	0	0
USO1	0	0	-9999	-10000	0	0
GBF1	0	0	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	-0.006	0.041	-9999	-0.29	10	10

×

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	-9999	-9999
FBXW11	0.01	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	0	-9999	-9999
beta TrCP1/SCF ubiquitin ligase complex	0.01	-9999	-9999
CHUK	0.01	-9999	-9999
NF kappa B2 p100/RelB	0	-9999	-9999
NFKB1	0.01	-9999	-9999
MAP3K14	0.01	-9999	-9999
NF kappa B1 p50/RelB	0	-9999	-9999
RELB	0.01	-9999	-9999
NFKB2	0.01	-9999	-9999
NF kappa B2 p52/RelB	0	-9999	-9999
regulation of B cell activation	0	-9999	-9999

pid_entity	TCGA.O1.A52J	TCGA.NJ.A55R	TCGA.NJ.A55O	TCGA.NJ.A55A
109_MAP3K5	0.043	0.043	0.043	0.043
47_PPARGC1A	0.0099	0.0099	0.0099	0.0099
105_BMP4	0.0099	0.0099	0.0099	0.0099
105_BMP6	-0.5	0.0099	0.0099	0.0099
105_BMP7	0.0099	0.0099	0.0099	0.0099
105_BMP2	0.0099	0.0099	0.0099	0.0099
131_RELN/VLDLR	-0.26	0	0	0
30_TGFB1/TGF beta receptor Type II	0.0094	0.014	0.0094	0.0094
84_STAT5B	0.035	0.037	0.022	-0.056
84_STAT5A	0.035	0.037	0.022	-0.056