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

Pathway.Name	Avg.Num.Perturbations
Glypican 2 network	145
Angiopoietin receptor Tie2-mediated signaling	106
FOXM1 transcription factor network	106
Aurora B signaling	101
Signaling events mediated by the Hedgehog family	79
Aurora C signaling	60
Endothelins	58
PLK1 signaling events	57
HIF-1-alpha transcription factor network	55
Visual signal transduction: Cones	47

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	0.3690	145	580	4	-0.2	-0.12	1000	-1000	-0.035	-1000
Angiopoietin receptor Tie2-mediated signaling	0.2697	106	9384	88	-0.56	0.053	1000	-1000	-0.11	-1000
FOXM1 transcription factor network	0.2697	106	5440	51	-0.6	0.01	1000	-1000	-0.19	-1000
Aurora B signaling	0.2570	101	6816	67	-0.43	0.01	1000	-1000	-0.059	-1000
Signaling events mediated by the Hedgehog family	0.2010	79	4129	52	-0.37	0.18	1000	-1000	-0.069	-1000
Aurora C signaling	0.1527	60	425	7	-0.27	0.005	1000	-1000	-0.031	-1000
Endothelins	0.1476	58	5603	96	-0.29	0.031	1000	-1000	-0.067	-1000
PLK1 signaling events	0.1450	57	4880	85	-0.31	0.064	1000	-1000	-0.049	-1000
HIF-1-alpha transcription factor network	0.1399	55	4205	76	-0.5	0.016	1000	-1000	-0.16	-1000
Visual signal transduction: Cones	0.1196	47	1796	38	-0.16	0.01	1000	-1000	-0.051	-1000
Osteopontin-mediated events	0.1170	46	1767	38	-0.38	0.011	1000	-1000	-0.088	-1000
IL4-mediated signaling events	0.1170	46	4264	91	-0.81	0.54	1000	-1000	-0.17	-1000
amb2 Integrin signaling	0.1043	41	3414	82	-0.47	0.01	1000	-1000	-0.071	-1000
BMP receptor signaling	0.1018	40	3261	81	-0.37	0.027	1000	-1000	-0.076	-1000
Fc-epsilon receptor I signaling in mast cells	0.0967	38	3722	97	-0.15	0.028	1000	-1000	-0.075	-1000
Signaling mediated by p38-alpha and p38-beta	0.0967	38	1674	44	-0.11	0.01	1000	-1000	-0.048	-1000
Signaling events regulated by Ret tyrosine kinase	0.0916	36	3033	82	-0.17	0.01	1000	-1000	-0.079	-1000
FOXA2 and FOXA3 transcription factor networks	0.0891	35	1634	46	-0.49	0.016	1000	-1000	-0.09	-1000
TCGA08_retinoblastoma	0.0891	35	280	8	-0.15	0.047	1000	-1000	-0.019	-1000
TCGA08_p53	0.0840	33	234	7	-0.1	0.052	1000	-1000	-0.017	-1000
Visual signal transduction: Rods	0.0789	31	1623	52	-0.16	0.01	1000	-1000	-0.074	-1000
LPA4-mediated signaling events	0.0763	30	360	12	-0.12	0.013	1000	-1000	-0.027	-1000
Glucocorticoid receptor regulatory network	0.0763	30	3525	114	-0.4	0.24	1000	-1000	-0.072	-1000
p75(NTR)-mediated signaling	0.0738	29	3648	125	-0.29	0.019	1000	-1000	-0.084	-1000
Arf6 signaling events	0.0712	28	1762	62	-0.19	0.011	1000	-1000	-0.056	-1000
Canonical Wnt signaling pathway	0.0687	27	1404	51	-0.34	0.15	1000	-1000	-0.057	-1000
Ephrin B reverse signaling	0.0662	26	1275	48	-0.1	0.061	1000	-1000	-0.062	-1000
Integrins in angiogenesis	0.0662	26	2193	84	-0.38	0.025	1000	-1000	-0.071	-1000
Effects of Botulinum toxin	0.0636	25	652	26	-0.081	0.01	1000	-1000	-0.053	-1000
EGFR-dependent Endothelin signaling events	0.0636	25	525	21	-0.095	0.01	1000	-1000	-0.054	-1000
Syndecan-1-mediated signaling events	0.0611	24	817	34	-0.35	0.01	1000	-1000	-0.055	-1000
Glypican 1 network	0.0611	24	1199	48	-0.1	0.019	1000	-1000	-0.043	-1000
Thromboxane A2 receptor signaling	0.0585	23	2465	105	-0.095	0.03	1000	-1000	-0.067	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0585	23	1627	68	-0.14	0.032	1000	-1000	-0.12	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0585	23	2855	120	-0.24	0.2	1000	-1000	-0.06	-1000
ErbB4 signaling events	0.0560	22	1528	69	-0.19	0.2	1000	-1000	-0.083	-1000
Aurora A signaling	0.0560	22	1358	60	-0.3	0.016	1000	-1000	-0.053	-1000
Presenilin action in Notch and Wnt signaling	0.0509	20	1240	61	-0.34	0.02	1000	-1000	-0.063	-1000
IL6-mediated signaling events	0.0509	20	1573	75	-0.33	0.042	1000	-1000	-0.091	-1000
IL23-mediated signaling events	0.0509	20	1234	60	-0.28	0.015	1000	-1000	-0.18	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0509	20	670	33	-0.14	0.024	1000	-1000	-0.053	-1000
PDGFR-alpha signaling pathway	0.0458	18	812	44	-0.3	0.026	1000	-1000	-0.051	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0458	18	951	52	-0.24	0.042	1000	-1000	-0.048	-1000
Class IB PI3K non-lipid kinase events	0.0458	18	54	3	-0.014	-1000	1000	-1000	-0.021	-1000
Nongenotropic Androgen signaling	0.0433	17	924	52	-0.056	0.01	1000	-1000	-0.056	-1000
Wnt signaling	0.0433	17	124	7	-0.062	0.009	1000	-1000	-0.028	-1000
PLK2 and PLK4 events	0.0407	16	48	3	-0.021	-0.005	1000	-1000	-0.014	-1000
HIF-2-alpha transcription factor network	0.0407	16	696	43	-0.14	0.069	1000	-1000	-0.088	-1000
Syndecan-3-mediated signaling events	0.0407	16	593	35	-0.2	0.01	1000	-1000	-0.054	-1000
Regulation of Androgen receptor activity	0.0382	15	1077	70	-0.25	0.028	1000	-1000	-0.059	-1000
Syndecan-2-mediated signaling events	0.0356	14	996	69	-0.097	0.032	1000	-1000	-0.047	-1000
Syndecan-4-mediated signaling events	0.0356	14	967	67	-0.19	0.014	1000	-1000	-0.073	-1000
Coregulation of Androgen receptor activity	0.0331	13	990	76	-0.14	0.018	1000	-1000	-0.053	-1000
Reelin signaling pathway	0.0331	13	760	56	-0.097	0.01	1000	-1000	-0.072	-1000
Noncanonical Wnt signaling pathway	0.0305	12	334	26	-0.062	0.01	1000	-1000	-0.07	-1000
IL12-mediated signaling events	0.0280	11	1023	87	-0.095	0.04	1000	-1000	-0.12	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0280	11	599	54	-0.14	0.021	1000	-1000	-0.082	-1000
Nectin adhesion pathway	0.0280	11	728	63	-0.035	0.018	1000	-1000	-0.064	-1000
LPA receptor mediated events	0.0280	11	1131	102	-0.11	0.03	1000	-1000	-0.073	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0280	11	892	78	-0.041	0.037	1000	-1000	-0.078	-1000
Caspase cascade in apoptosis	0.0254	10	766	74	-0.052	0.029	1000	-1000	-0.044	-1000
Ephrin A reverse signaling	0.0254	10	72	7	-0.012	0.006	1000	-1000	-0.022	-1000
Signaling events mediated by PTP1B	0.0254	10	824	76	-0.094	0.016	1000	-1000	-0.071	-1000
Signaling events mediated by HDAC Class III	0.0254	10	424	40	-0.11	0.018	1000	-1000	-0.037	-1000
FAS signaling pathway (CD95)	0.0254	10	483	47	-0.24	0.013	1000	-1000	-0.045	-1000
Signaling events mediated by PRL	0.0254	10	341	34	-0.18	0.02	1000	-1000	-0.037	-1000
BARD1 signaling events	0.0229	9	513	57	-0.18	0.031	1000	-1000	-0.055	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0229	9	849	85	-0.046	0.032	1000	-1000	-0.064	-1000
IL1-mediated signaling events	0.0229	9	600	62	-0.14	0.049	1000	-1000	-0.078	-1000
S1P1 pathway	0.0229	9	354	36	-0.06	0.012	1000	-1000	-0.052	-1000
Calcium signaling in the CD4+ TCR pathway	0.0229	9	284	31	-0.1	0.011	1000	-1000	-0.082	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0229	9	1215	125	-0.3	0.039	1000	-1000	-0.086	-1000
BCR signaling pathway	0.0229	9	982	99	-0.13	0.027	1000	-1000	-0.074	-1000
ErbB2/ErbB3 signaling events	0.0204	8	528	65	-0.089	0.02	1000	-1000	-0.06	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0204	8	304	34	-0.031	0.013	1000	-1000	-0.054	-1000
TCR signaling in naïve CD8+ T cells	0.0204	8	781	93	-0.07	0.042	1000	-1000	-0.073	-1000
IL2 signaling events mediated by STAT5	0.0204	8	178	22	-0.13	0.055	1000	-1000	-0.056	-1000
Arf6 trafficking events	0.0204	8	577	71	-0.084	0.034	1000	-1000	-0.056	-1000
EPHB forward signaling	0.0178	7	656	85	-0.067	0.05	1000	-1000	-0.078	-1000
Regulation of p38-alpha and p38-beta	0.0178	7	386	54	-0.066	0.02	1000	-1000	-0.056	-1000
Plasma membrane estrogen receptor signaling	0.0178	7	622	86	-0.036	0.03	1000	-1000	-0.074	-1000
S1P4 pathway	0.0178	7	188	25	-0.036	0.01	1000	-1000	-0.049	-1000
Regulation of nuclear SMAD2/3 signaling	0.0153	6	921	136	-0.11	0.051	1000	-1000	-0.064	-1000
S1P5 pathway	0.0153	6	113	17	-0.036	0.03	1000	-1000	-0.049	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0127	5	159	28	-0.036	0.02	1000	-1000	-0.051	-1000
Cellular roles of Anthrax toxin	0.0127	5	207	39	-0.043	0.016	1000	-1000	-0.025	-1000
Signaling mediated by p38-gamma and p38-delta	0.0127	5	80	15	0	0.02	1000	-1000	-0.029	-1000
IL27-mediated signaling events	0.0127	5	275	51	-0.1	0.011	1000	-1000	-0.068	-1000
Regulation of Telomerase	0.0127	5	589	102	-0.097	0.032	1000	-1000	-0.096	-1000
Insulin Pathway	0.0127	5	387	74	-0.15	0.03	1000	-1000	-0.08	-1000
VEGFR1 specific signals	0.0127	5	297	56	-0.3	0.042	1000	-1000	-0.063	-1000
Signaling events mediated by HDAC Class II	0.0102	4	324	75	-0.046	0.027	1000	-1000	-0.051	-1000
Hedgehog signaling events mediated by Gli proteins	0.0102	4	324	65	-0.17	0.054	1000	-1000	-0.059	-1000
Ceramide signaling pathway	0.0102	4	328	76	-0.095	0.032	1000	-1000	-0.057	-1000
Signaling events mediated by HDAC Class I	0.0102	4	456	104	-0.055	0.043	1000	-1000	-0.056	-1000
Retinoic acid receptors-mediated signaling	0.0102	4	278	58	-0.16	0.033	1000	-1000	-0.065	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0102	4	316	74	-0.11	0.061	1000	-1000	-0.072	-1000
Class I PI3K signaling events	0.0102	4	304	73	-0.06	0.025	1000	-1000	-0.054	-1000
p38 MAPK signaling pathway	0.0102	4	218	44	-0.077	0.026	1000	-1000	-0.06	-1000
Ras signaling in the CD4+ TCR pathway	0.0102	4	82	17	-0.013	0.02	1000	-1000	-0.036	-1000
Circadian rhythm pathway	0.0076	3	84	22	-0.033	0.034	1000	-1000	-0.052	-1000
JNK signaling in the CD4+ TCR pathway	0.0076	3	67	17	-0.013	0.031	1000	-1000	-0.057	-1000
Arf6 downstream pathway	0.0076	3	161	43	-0.052	0.027	1000	-1000	-0.04	-1000
IFN-gamma pathway	0.0076	3	241	68	-0.076	0.047	1000	-1000	-0.086	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0076	3	317	83	-0.064	0.04	1000	-1000	-0.078	-1000
FoxO family signaling	0.0076	3	250	64	-0.14	0.055	1000	-1000	-0.09	-1000
IL2 signaling events mediated by PI3K	0.0076	3	201	58	-0.14	0.066	1000	-1000	-0.078	-1000
S1P3 pathway	0.0076	3	134	42	-0.035	0.021	1000	-1000	-0.052	-1000
TRAIL signaling pathway	0.0051	2	108	48	-0.01	0.04	1000	-1000	-0.056	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0051	2	122	45	-0.02	0.061	1000	-1000	-0.084	-1000
TCGA08_rtk_signaling	0.0051	2	75	26	-0.025	0.037	1000	-1000	-0.021	-1000
E-cadherin signaling in the nascent adherens junction	0.0051	2	175	76	-0.053	0.05	1000	-1000	-0.072	-1000
IGF1 pathway	0.0051	2	118	57	-0.039	0.042	1000	-1000	-0.081	-1000
Rapid glucocorticoid signaling	0.0051	2	48	20	-0.006	0.01	1000	-1000	-0.035	-1000
PDGFR-beta signaling pathway	0.0051	2	199	97	-0.041	0.049	1000	-1000	-0.07	-1000
Canonical NF-kappaB pathway	0.0025	1	54	39	-0.021	0.066	1000	-1000	-0.073	-1000
a4b1 and a4b7 Integrin signaling	0.0025	1	8	5	-0.003	0.009	1000	-1000	-0.035	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0025	1	47	37	-0.005	0.028	1000	-1000	-0.058	-1000
ceramide signaling pathway	0.0025	1	72	49	-0.02	0.036	1000	-1000	-0.046	-1000
E-cadherin signaling events	0.0025	1	8	5	-0.002	0.01	1000	-1000	-0.038	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	9	23	-0.003	0.036	1000	-1000	-0.061	-1000
EPO signaling pathway	0.0000	0	44	55	-0.005	0.06	1000	-1000	-0.076	-1000
Insulin-mediated glucose transport	0.0000	0	23	32	-0.004	0.035	1000	-1000	-0.058	-1000
mTOR signaling pathway	0.0000	0	10	53	-0.001	0.027	1000	-1000	-0.052	-1000
Class I PI3K signaling events mediated by Akt	0.0000	0	22	68	-0.034	0.046	1000	-1000	-0.056	-1000
Paxillin-dependent events mediated by a4b1	0.0000	0	15	36	-0.004	0.018	1000	-1000	-0.063	-1000
Atypical NF-kappaB pathway	0.0000	0	12	31	-0.002	0.038	1000	-1000	-0.058	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	14	27	-0.002	0.023	1000	-1000	-0.047	-1000
E-cadherin signaling in keratinocytes	0.0000	0	26	43	-0.008	0.038	1000	-1000	-0.057	-1000
Arf1 pathway	0.0000	0	16	54	-0.006	0.024	1000	-1000	-0.038	-1000
Alternative NF-kappaB pathway	0.0000	0	0	13	0	0.01	1000	-1000	-0.047	-1000
Total	NA	2309	134038	7203	-19	-1000	131000	-131000	-8.3	-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	-0.16	0.25	-9999	-0.52	126	126
GPC2	-0.12	0.22	-9999	-0.52	94	94
GPC2/Midkine	-0.2	0.24	-9999	-0.44	180	180
neuron projection morphogenesis	-0.2	0.24	-9999	-0.44	180	180

×

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	-0.39	0.51	-10000	0	-0.95	173	173
NCK1/PAK1/Dok-R	-0.2	0.21	-10000	0	-0.43	173	173
NCK1/Dok-R	-0.51	0.6	-10000	0	-1.1	173	173
PIK3CA	0.011	0.001	-10000	0	-10000	0	0
mol:beta2-estradiol	0.053	0.1	0.24	86	-10000	0	86
RELA	0.01	0	-10000	0	-10000	0	0
SHC1	0.006	0.005	-10000	0	-10000	0	0
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	0.004	0.2	0.25	82	-0.52	39	121
TNIP2	0.01	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.46	0.54	-10000	0	-1	173	173
FN1	0.005	0.051	-10000	0	-0.5	4	4
PLD2	-0.49	0.66	-10000	0	-1.2	173	173
PTPN11	0.01	0	-10000	0	-10000	0	0
GRB14	-0.028	0.14	-10000	0	-0.52	28	28
ELK1	-0.42	0.57	-10000	0	-1	173	173
GRB7	0.003	0.058	-10000	0	-0.51	5	5
PAK1	0.01	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.48	0.58	-10000	0	-1.1	173	173
CDKN1A	-0.26	0.35	-10000	0	-0.65	169	169
ITGA5	0.007	0.037	-10000	0	-0.51	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.51	0.6	-10000	0	-1.1	173	173
CRK	0.01	0	-10000	0	-10000	0	0
mol:NO	-0.27	0.37	-10000	0	-0.68	173	173
PLG	-0.5	0.66	-10000	0	-1.2	173	173
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.37	0.48	-10000	0	-0.89	173	173
GRB2	0.01	0	-10000	0	-10000	0	0
PIK3R1	0.006	0.005	-10000	0	-10000	0	0
ANGPT2	-0.2	0.28	-10000	0	-0.68	78	78
BMX	-0.56	0.68	-10000	0	-1.3	173	173
ANGPT1	-0.28	0.52	-10000	0	-1.3	86	86
tube development	-0.3	0.39	-10000	0	-0.73	171	171
ANGPT4	-0.26	0.25	-10000	0	-0.5	203	203
response to hypoxia	-0.027	0.035	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.52	0.69	-10000	0	-1.2	173	173
alpha5/beta1 Integrin	-0.002	0.026	-10000	0	-0.36	2	2
FGF2	-0.056	0.17	-10000	0	-0.5	49	49
STAT5A (dimer)	-0.35	0.46	-10000	0	-0.85	169	169
mol:L-citrulline	-0.27	0.37	-10000	0	-0.68	173	173
AGTR1	-0.14	0.23	-10000	0	-0.5	116	116
MAPK14	-0.51	0.66	-10000	0	-1.2	173	173
Tie2/SHP2	-0.44	0.54	-10000	0	-1.1	151	151
TEK	-0.48	0.61	-10000	0	-1.2	151	151
RPS6KB1	-0.37	0.49	-10000	0	-0.9	173	173
Angiotensin II/AT1	-0.1	0.17	-10000	0	-0.36	116	116
Tie2/Ang1/GRB2	-0.51	0.68	-10000	0	-1.2	173	173
MAPK3	-0.43	0.58	-10000	0	-1.1	173	173
MAPK1	-0.43	0.58	-10000	0	-1.1	173	173
Tie2/Ang1/GRB7	-0.51	0.68	-10000	0	-1.2	173	173
NFKB1	0.01	0	-10000	0	-10000	0	0
MAPK8	-0.49	0.66	-10000	0	-1.2	173	173
PI3K	-0.46	0.6	-10000	0	-1.1	173	173
FES	-0.51	0.66	-10000	0	-1.2	173	173
Crk/Dok-R	-0.51	0.6	-10000	0	-1.1	173	173
Tie2/Ang1/ABIN2	-0.51	0.68	-10000	0	-1.2	173	173
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.34	0.45	-10000	0	-0.83	173	173
STAT5A	0.009	0.026	-10000	0	-0.5	1	1
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.37	0.49	-10000	0	-0.9	173	173
Tie2/Ang2	-0.44	0.56	-10000	0	-1.1	171	171
Tie2/Ang1	-0.55	0.74	-10000	0	-1.3	173	173
FOXO1	-0.34	0.45	-10000	0	-0.84	173	173
ELF1	-0.024	0.05	-10000	0	-10000	0	0
ELF2	-0.5	0.66	-10000	0	-1.2	173	173
mol:Choline	-0.46	0.61	-10000	0	-1.1	173	173
cell migration	-0.11	0.12	-10000	0	-0.24	173	173
FYN	-0.35	0.45	-10000	0	-0.85	171	171
DOK2	-0.034	0.14	-10000	0	-0.5	34	34
negative regulation of cell cycle	-0.23	0.32	-10000	0	-0.58	169	169
ETS1	-0.04	0.096	-10000	0	-0.25	15	15
PXN	-0.29	0.4	-10000	0	-0.73	173	173
ITGB1	0.01	0	-10000	0	-10000	0	0
NOS3	-0.32	0.42	-10000	0	-0.78	173	173
RAC1	0.01	0	-10000	0	-10000	0	0
TNF	-0.071	0.15	-10000	0	-0.55	23	23
MAPKKK cascade	-0.46	0.61	-10000	0	-1.1	173	173
RASA1	0.01	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.52	0.67	-10000	0	-1.2	173	173
NCK1	0.01	0	-10000	0	-10000	0	0
vasculogenesis	-0.24	0.33	-10000	0	-0.6	173	173
mol:Phosphatidic acid	-0.46	0.61	-10000	0	-1.1	173	173
mol:Angiotensin II	0.001	0.002	-10000	0	-10000	0	0
mol:NADP	-0.27	0.37	-10000	0	-0.68	173	173
Rac1/GTP	-0.37	0.42	-10000	0	-0.84	173	173
MMP2	-0.49	0.66	-10000	0	-1.2	173	173

×

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	-0.47	0.55	-9999	-1	141	141
PLK1	-0.16	0.2	-9999	-10000	0	0
BIRC5	-0.2	0.2	-9999	-10000	0	0
HSPA1B	-0.47	0.55	-9999	-1	142	142
MAP2K1	-0.003	0.034	-9999	-10000	0	0
BRCA2	-0.47	0.55	-9999	-1.1	140	140
FOXM1	-0.6	0.71	-9999	-1.3	155	155
XRCC1	-0.47	0.55	-9999	-1	142	142
FOXM1B/p19	-0.54	0.49	-9999	-1.1	152	152
Cyclin D1/CDK4	-0.46	0.51	-9999	-0.98	143	143
CDC2	-0.5	0.58	-9999	-1.1	152	152
TGFA	-0.45	0.5	-9999	-0.95	143	143
SKP2	-0.47	0.55	-9999	-1.1	140	140
CCNE1	-0.19	0.26	-9999	-0.53	142	142
CKS1B	-0.47	0.55	-9999	-1.1	141	141
RB1	-0.23	0.18	-9999	-0.47	29	29
FOXM1C/SP1	-0.53	0.62	-9999	-1.2	151	151
AURKB	-0.18	0.2	-9999	-10000	0	0
CENPF	-0.53	0.59	-9999	-1.1	157	157
CDK4	0.002	0.048	-9999	-0.54	3	3
MYC	-0.4	0.48	-9999	-0.91	140	140
CHEK2	-0.011	0.077	-9999	-0.57	6	6
ONECUT1	-0.5	0.55	-9999	-1	156	156
CDKN2A	-0.14	0.24	-9999	-0.51	115	115
LAMA4	-0.47	0.55	-9999	-1.1	145	145
FOXM1B/HNF6	-0.59	0.65	-9999	-1.3	154	154
FOS	-0.49	0.58	-9999	-1.1	144	144
SP1	0.01	0.001	-9999	-10000	0	0
CDC25B	-0.47	0.55	-9999	-1	142	142
response to radiation	-0.014	0.031	-9999	-10000	0	0
CENPB	-0.47	0.55	-9999	-1.1	135	135
CENPA	-0.54	0.6	-9999	-1.1	169	169
NEK2	-0.55	0.6	-9999	-1.1	172	172
HIST1H2BA	-0.47	0.55	-9999	-1.1	140	140
CCNA2	-0.13	0.24	-9999	-0.53	103	103
EP300	0.01	0	-9999	-10000	0	0
CCNB1/CDK1	-0.56	0.64	-9999	-1.3	143	143
CCNB2	-0.53	0.6	-9999	-1.1	166	166
CCNB1	-0.52	0.6	-9999	-1.2	143	143
ETV5	-0.47	0.56	-9999	-1.1	136	136
ESR1	-0.48	0.56	-9999	-1.1	139	139
CCND1	-0.47	0.52	-9999	-1	144	144
GSK3A	0.001	0.028	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	-0.19	0.26	-9999	-0.47	168	168
CDK2	0.006	0.008	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.017	0.038	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.58	0.5	-9999	-1.1	167	167
GAS1	-0.48	0.56	-9999	-1.1	147	147
MMP2	-0.47	0.55	-9999	-1	142	142
RB1/FOXM1C	-0.5	0.56	-9999	-1.1	151	151
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	170	170
STMN1	-0.19	0.2	-9999	-0.37	209	209
Aurora B/RasGAP/Survivin	-0.32	0.27	-9999	-0.51	249	249
Chromosomal passenger complex/Cul3 protein complex	-0.14	0.14	-9999	-0.3	134	134
BIRC5	-0.31	0.26	-9999	-0.53	233	233
DES	-0.42	0.37	-9999	-0.75	215	215
Aurora C/Aurora B/INCENP	-0.14	0.15	-9999	-0.28	212	212
Aurora B/TACC1	-0.17	0.17	-9999	-0.32	214	214
Aurora B/PP2A	-0.19	0.19	-9999	-0.36	209	209
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.034	0.045	-9999	-10000	0	0
mitotic metaphase/anaphase transition	-0.003	0.004	-9999	-10000	0	0
NDC80	-0.35	0.32	-9999	-0.6	234	234
Cul3 protein complex	-0.013	0.065	-9999	-0.31	17	17
KIF2C	-0.13	0.11	-9999	-0.23	203	203
PEBP1	0.004	0.005	-9999	-10000	0	0
KIF20A	-0.29	0.26	-9999	-0.52	223	223
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.19	0.19	-9999	-0.36	209	209
SEPT1	0.009	0.026	-9999	-0.5	1	1
SMC2	0.01	0	-9999	-10000	0	0
SMC4	0.01	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.066	0.076	-9999	-10000	0	0
PSMA3	0.01	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.002	0.003	-9999	-10000	0	0
H3F3B	-0.092	0.1	-9999	-0.19	209	209
AURKB	-0.27	0.27	-9999	-0.52	209	209
AURKC	0.005	0.052	-9999	-0.51	4	4
CDCA8	-0.19	0.26	-9999	-0.53	143	143
cytokinesis	-0.24	0.21	-9999	-0.43	195	195
Aurora B/Septin1	-0.22	0.2	-9999	-0.43	173	173
AURKA	-0.1	0.22	-9999	-0.52	84	84
INCENP	0.002	0.007	-9999	-10000	0	0
KLHL13	-0.011	0.1	-9999	-0.5	16	16
BUB1	-0.14	0.24	-9999	-0.52	112	112
hSgo1/Aurora B/Survivin	-0.43	0.36	-9999	-0.67	254	254
EVI5	0.009	0.002	-9999	-10000	0	0
RhoA/GTP	-0.23	0.23	-9999	-0.47	166	166
SGOL1	-0.25	0.26	-9999	-0.52	194	194
CENPA	-0.17	0.16	-9999	-0.31	207	207
NCAPG	-0.23	0.26	-9999	-0.52	175	175
Aurora B/HC8 Proteasome	-0.19	0.19	-9999	-0.36	209	209
NCAPD2	0.008	0.027	-9999	-0.52	1	1
Aurora B/PP1-gamma	-0.19	0.19	-9999	-0.36	209	209
RHOA	0.01	0	-9999	-10000	0	0
NCAPH	-0.23	0.26	-9999	-0.52	179	179
NPM1	-0.087	0.083	-9999	-10000	0	0
RASA1	0.01	0	-9999	-10000	0	0
KLHL9	0.007	0.036	-9999	-0.5	2	2
mitotic prometaphase	-0.009	0.008	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.19	0.19	-9999	-0.36	209	209
PPP1CC	0.01	0	-9999	-10000	0	0
Centraspindlin	-0.25	0.25	-9999	-0.48	187	187
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.087	0.083	-9999	-10000	0	0
MYLK	-0.1	0.12	-9999	-0.2	211	211
KIF23	-0.12	0.23	-9999	-0.53	97	97
VIM	-0.18	0.19	-9999	-0.37	209	209
RACGAP1	-0.001	0.054	-9999	-0.53	4	4
mitosis	0	0	-9999	-10000	0	0
NCL	-0.087	0.083	-9999	-10000	0	0
Chromosomal passenger complex	-0.2	0.2	-9999	-0.38	205	205
Chromosomal passenger complex/EVI5	-0.35	0.33	-9999	-0.64	205	205
TACC1	-0.011	0.1	-9999	-0.5	16	16
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	-0.66	70	70
IHH	-0.31	0.27	-10000	0	-0.54	221	221
SHH Np/Cholesterol/GAS1	-0.041	0.1	-10000	0	-0.28	58	58
LRPAP1	0.01	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.041	0.1	0.28	58	-10000	0	58
SMO/beta Arrestin2	-0.21	0.22	-10000	0	-0.51	79	79
SMO	-0.22	0.23	-10000	0	-0.54	80	80
AKT1	-0.091	0.1	-10000	0	-0.3	8	8
ARRB2	0.01	0	-10000	0	-10000	0	0
BOC	0.007	0.037	-10000	0	-0.51	2	2
ADRBK1	0.01	0	-10000	0	-10000	0	0
heart looping	-0.22	0.22	-10000	0	-0.53	80	80
STIL	-0.2	0.22	-10000	0	-0.48	112	112
DHH N/PTCH2	-0.025	0.091	-10000	0	-0.35	28	28
DHH N/PTCH1	-0.19	0.19	-10000	0	-0.48	75	75
PIK3CA	0.01	0	-10000	0	-10000	0	0
DHH	-0.026	0.13	-10000	0	-0.5	27	27
PTHLH	-0.28	0.29	-10000	0	-0.78	70	70
determination of left/right symmetry	-0.22	0.22	-10000	0	-0.53	80	80
PIK3R1	0.01	0	-10000	0	-10000	0	0
skeletal system development	-0.27	0.29	-10000	0	-0.77	70	70
IHH N/Hhip	-0.37	0.26	-10000	0	-0.49	297	297
DHH N/Hhip	-0.22	0.2	-10000	0	-0.38	223	223
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.22	0.22	-10000	0	-0.53	80	80
pancreas development	-0.27	0.25	-10000	0	-0.5	214	214
HHAT	0.007	0.036	-10000	0	-0.5	2	2
PI3K	0	0	-10000	0	-10000	0	0
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.004	0.084	-10000	0	-0.5	11	11
somite specification	-0.22	0.22	-10000	0	-0.53	80	80
SHH Np/Cholesterol/PTCH1	-0.18	0.2	-10000	0	-0.46	88	88
SHH Np/Cholesterol/PTCH2	-0.034	0.089	-10000	0	-0.26	51	51
SHH Np/Cholesterol/Megalin	-0.11	0.15	-10000	0	-0.3	141	141
SHH	-0.03	0.12	-10000	0	-0.36	50	50
catabolic process	-0.2	0.2	-10000	0	-0.52	62	62
SMO/Vitamin D3	-0.2	0.22	-10000	0	-0.51	85	85
SHH Np/Cholesterol/Hhip	-0.18	0.16	-10000	0	-0.3	232	232
LRP2	-0.13	0.23	-10000	0	-0.5	108	108
receptor-mediated endocytosis	-0.26	0.23	-10000	0	-0.53	131	131
SHH Np/Cholesterol/BOC	-0.035	0.09	-10000	0	-0.26	52	52
SHH Np/Cholesterol/CDO	-0.04	0.098	-10000	0	-0.27	57	57
mesenchymal cell differentiation	0.18	0.16	0.3	232	-10000	0	232
mol:Vitamin D3	-0.18	0.2	-10000	0	-0.47	88	88
IHH N/PTCH2	-0.18	0.17	-10000	0	-0.32	221	221
CDON	-0.002	0.076	-10000	0	-0.5	9	9
IHH N/PTCH1	-0.2	0.2	-10000	0	-0.53	62	62
Megalin/LRPAP1	-0.097	0.16	-10000	0	-0.35	108	108
PTCH2	0.008	0.026	-10000	0	-0.5	1	1
SHH Np/Cholesterol	-0.035	0.091	-10000	0	-0.27	50	50
PTCH1	-0.2	0.2	-10000	0	-0.52	62	62
HHIP	-0.27	0.25	-10000	0	-0.5	214	214

×

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	212	212
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.043	0.04	-9999	-10000	0	0
AURKB	-0.27	0.26	-9999	-0.52	209	209
AURKC	0.005	0.052	-9999	-0.51	4	4

×

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	-0.045	0.2	0.26	1	-0.45	49	50
PTK2B	0.007	0.036	-10000	0	-0.5	2	2
mol:Ca2+	-0.045	0.27	-10000	0	-0.94	29	29
EDN1	-0.061	0.22	0.21	1	-0.54	60	61
EDN3	-0.14	0.23	-10000	0	-0.5	109	109
EDN2	-0.14	0.24	-10000	0	-0.52	110	110
HRAS/GDP	-0.076	0.2	-10000	0	-0.47	52	52
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.003	0.14	-10000	0	-0.37	26	26
ADCY4	-0.065	0.17	-10000	0	-0.48	36	36
ADCY5	-0.09	0.2	-10000	0	-0.51	52	52
ADCY6	-0.052	0.16	-10000	0	-0.46	32	32
ADCY7	-0.053	0.16	-10000	0	-0.45	34	34
ADCY1	-0.057	0.16	-10000	0	-0.46	35	35
ADCY2	-0.078	0.18	-10000	0	-0.48	43	43
ADCY3	-0.052	0.16	-10000	0	-0.46	32	32
ADCY8	-0.16	0.18	-10000	0	-0.44	79	79
ADCY9	-0.058	0.16	-10000	0	-0.46	35	35
arachidonic acid secretion	-0.068	0.2	-10000	0	-0.48	56	56
ETB receptor/Endothelin-1/Gq/GTP	-0.15	0.2	-10000	0	-0.36	134	134
GNAO1	0.005	0.052	-10000	0	-0.51	4	4
HRAS	0.009	0.002	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	0.031	0.22	0.23	144	-0.41	49	193
ETA receptor/Endothelin-1/Gs/GTP	0.021	0.22	0.22	141	-0.41	52	193
mol:GTP	0	0.005	-10000	0	-10000	0	0
COL3A1	-0.098	0.26	-10000	0	-0.45	122	122
EDNRB	-0.27	0.25	-10000	0	-0.5	219	219
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.054	0.22	-10000	0	-0.64	29	29
CYSLTR1	-0.055	0.23	-10000	0	-0.61	35	35
SLC9A1	-0.019	0.11	0.18	1	-0.3	23	24
mol:GDP	-0.087	0.22	-10000	0	-0.51	53	53
SLC9A3	-0.28	0.35	-10000	0	-0.54	225	225
RAF1	-0.09	0.22	-10000	0	-0.52	53	53
JUN	-0.013	0.19	-10000	0	-0.67	17	17
JAK2	-0.046	0.2	0.26	1	-0.45	50	51
mol:IP3	-0.088	0.18	-10000	0	-0.41	61	61
ETA receptor/Endothelin-1	-0.015	0.28	0.26	144	-0.49	59	203
PLCB1	0.008	0.027	-10000	0	-0.52	1	1
PLCB2	-0.002	0.077	-10000	0	-0.5	9	9
ETA receptor/Endothelin-3	-0.096	0.18	-10000	0	-0.37	111	111
FOS	-0.092	0.28	-10000	0	-0.87	36	36
Gai/GDP	-0.01	0.088	-10000	0	-0.58	3	3
CRK	0.01	0.001	-10000	0	-10000	0	0
mol:Ca ++	-0.14	0.26	-10000	0	-0.57	75	75
BCAR1	0.009	0.026	-10000	0	-0.5	1	1
PRKCB1	-0.085	0.18	-10000	0	-0.39	63	63
GNAQ	0.009	0.026	-10000	0	-0.5	1	1
GNAZ	-0.036	0.15	-10000	0	-0.5	35	35
GNAL	-0.002	0.078	-10000	0	-0.51	9	9
Gs family/GDP	-0.11	0.17	-10000	0	-0.46	54	54
ETA receptor/Endothelin-1/Gq/GTP	-0.006	0.14	-10000	0	-0.36	33	33
MAPK14	-0.12	0.18	-10000	0	-0.42	65	65
TRPC6	-0.051	0.29	-10000	0	-1	29	29
GNAI2	0.01	0	-10000	0	-10000	0	0
GNAI3	0.01	0	-10000	0	-10000	0	0
GNAI1	0.007	0.036	-10000	0	-0.5	2	2
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.13	0.19	-10000	0	-0.37	103	103
ETB receptor/Endothelin-2	-0.29	0.24	-10000	0	-0.44	260	260
ETB receptor/Endothelin-3	-0.29	0.23	-10000	0	-0.43	264	264
ETB receptor/Endothelin-1	-0.24	0.26	-10000	0	-0.44	226	226
MAPK3	-0.096	0.27	-10000	0	-0.76	43	43
MAPK1	-0.096	0.27	-10000	0	-0.77	42	42
Rac1/GDP	-0.076	0.2	-10000	0	-0.47	51	51
cAMP biosynthetic process	-0.1	0.19	-10000	0	-0.49	53	53
MAPK8	-0.023	0.2	-10000	0	-0.58	31	31
SRC	0.01	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.14	0.18	-10000	0	-0.4	88	88
p130Cas/CRK/Src/PYK2	-0.084	0.23	-10000	0	-0.58	47	47
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.076	0.2	-10000	0	-0.47	51	51
COL1A2	-0.19	0.27	-10000	0	-0.62	85	85
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.099	0.19	-10000	0	-0.38	112	112
mol:DAG	-0.088	0.18	-10000	0	-0.41	61	61
MAP2K2	-0.088	0.23	-10000	0	-0.62	45	45
MAP2K1	-0.088	0.23	-10000	0	-0.62	45	45
EDNRA	0.011	0.11	-10000	0	-0.38	8	8
positive regulation of muscle contraction	-0.031	0.17	0.23	1	-0.46	29	30
Gq family/GDP	-0.076	0.17	-10000	0	-0.51	35	35
HRAS/GTP	-0.093	0.21	-10000	0	-0.46	57	57
PRKCH	-0.079	0.18	-10000	0	-0.47	38	38
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCA	-0.08	0.18	-10000	0	-0.48	39	39
PRKCB	-0.084	0.19	-10000	0	-0.51	40	40
PRKCE	-0.08	0.18	-10000	0	-0.47	40	40
PRKCD	-0.079	0.18	-10000	0	-0.47	38	38
PRKCG	-0.098	0.19	-10000	0	-0.48	51	51
regulation of vascular smooth muscle contraction	-0.11	0.32	-10000	0	-1	36	36
PRKCQ	-0.12	0.22	-10000	0	-0.46	78	78
PLA2G4A	-0.075	0.22	-10000	0	-0.52	56	56
GNA14	-0.005	0.09	-10000	0	-0.51	12	12
GNA15	0.01	0.004	-10000	0	-10000	0	0
GNA12	0.01	0	-10000	0	-10000	0	0
GNA11	0.009	0.026	-10000	0	-0.5	1	1
Rac1/GTP	0.031	0.22	0.23	144	-0.41	49	193
MMP1	-0.24	0.2	-10000	0	-0.38	228	228

×

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	0.064	0.072	0.14	194	-10000	0	194
BUB1B	-0.12	0.12	-10000	0	-0.21	245	245
PLK1	-0.028	0.051	-10000	0	-0.12	77	77
PLK1S1	-0.01	0.027	-10000	0	-0.11	1	1
KIF2A	-0.018	0.046	-10000	0	-0.18	1	1
regulation of mitotic centrosome separation	-0.028	0.051	-10000	0	-0.12	77	77
GOLGA2	0.01	0	-10000	0	-10000	0	0
Hec1/SPC24	-0.24	0.26	-10000	0	-0.45	214	214
WEE1	-0.026	0.056	-10000	0	-0.19	1	1
cytokinesis	-0.12	0.13	-10000	0	-0.25	170	170
PP2A-alpha B56	-0.016	0.035	-10000	0	-10000	0	0
AURKA	-0.022	0.046	-10000	0	-0.1	77	77
PICH/PLK1	-0.16	0.23	-10000	0	-0.41	165	165
CENPE	-0.083	0.15	-10000	0	-0.36	89	89
RhoA/GTP	0	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.018	0.046	-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	-0.047	0.053	-10000	0	-0.11	70	70
PAK1	0.008	0.004	-10000	0	-10000	0	0
SPC24	-0.16	0.25	-10000	0	-0.52	125	125
FBXW11	0.01	0	-10000	0	-10000	0	0
CLSPN	-0.04	0.058	-10000	0	-0.13	88	88
GORASP1	0.01	0	-10000	0	-10000	0	0
metaphase	-0.002	0.004	-10000	0	-0.011	76	76
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	-0.014	0.027	-10000	0	-0.059	71	71
G2 phase of mitotic cell cycle	-0.002	0.003	-10000	0	-0.014	1	1
STAG2	0.01	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	-0.001	0.011	-10000	0	-10000	0	0
spindle elongation	-0.028	0.051	-10000	0	-0.12	77	77
ODF2	0.008	0.004	-10000	0	-10000	0	0
BUB1	-0.025	0.042	-10000	0	-10000	0	0
TPT1	-0.01	0.027	-10000	0	-0.11	1	1
CDC25C	-0.067	0.061	-10000	0	-0.14	71	71
CDC25B	0.008	0.003	-10000	0	-10000	0	0
SGOL1	-0.064	0.072	-10000	0	-0.14	194	194
RHOA	0.01	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.075	0.11	-10000	0	-0.25	91	91
CDC14B	0.007	0.004	-10000	0	-10000	0	0
CDC20	-0.31	0.26	-10000	0	-0.52	237	237
PLK1/PBIP1	-0.052	0.094	-10000	0	-0.34	34	34
mitosis	-0.003	0.008	0.02	13	-0.018	71	84
FBXO5	-0.019	0.045	-10000	0	-0.17	1	1
CDC2	-0.003	0.005	-10000	0	-0.011	94	94
NDC80	-0.26	0.26	-10000	0	-0.52	203	203
metaphase plate congression	-0.016	0.033	-10000	0	-10000	0	0
ERCC6L	-0.16	0.2	-10000	0	-0.4	145	145
NLP/gamma Tubulin	-0.013	0.028	-10000	0	-0.11	2	2
microtubule cytoskeleton organization	-0.01	0.027	-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	-0.21	0.23	-10000	0	-0.39	223	223
GRASP65/GM130/RAB1/GTP/PLK1	-0.019	0.028	-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	-0.018	0.048	-10000	0	-0.37	1	1
mitotic prometaphase	-0.003	0.003	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.041	0.036	-10000	0	-10000	0	0
microtubule-based process	-0.18	0.17	-10000	0	-0.33	223	223
Golgi organization	-0.028	0.051	-10000	0	-0.12	77	77
Cohesin/SA2	-0.03	0.038	-10000	0	-0.17	1	1
PPP1CB/MYPT1	0	0	-10000	0	-10000	0	0
KIF20A	-0.29	0.26	-10000	0	-0.52	223	223
APC/C/CDC20	-0.19	0.17	-10000	0	-0.33	237	237
PPP2R1A	0.01	0	-10000	0	-10000	0	0
chromosome segregation	-0.051	0.093	-10000	0	-0.33	34	34
PRC1	-0.083	0.2	-10000	0	-0.52	69	69
ECT2	-0.037	0.097	-10000	0	-0.36	27	27
C13orf34	-0.017	0.046	-10000	0	-0.36	1	1
NUDC	-0.016	0.033	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.12	0.12	-10000	0	-0.21	245	245
spindle assembly	-0.02	0.041	-10000	0	-0.091	64	64
spindle stabilization	-0.01	0.027	-10000	0	-0.11	1	1
APC/C/HCDH1	0.011	0.006	-10000	0	-10000	0	0
MKLP2/PLK1	-0.18	0.17	-10000	0	-0.33	223	223
CCNB1	-0.16	0.24	-10000	0	-0.52	124	124
PPP1CB	0.009	0.001	-10000	0	-10000	0	0
BTRC	0.01	0	-10000	0	-10000	0	0
ROCK2	-0.009	0.035	-10000	0	-10000	0	0
TUBG1	-0.01	0.027	-10000	0	-0.11	2	2
G2/M transition of mitotic cell cycle	-0.075	0.11	-10000	0	-0.24	91	91
MLF1IP	-0.029	0.11	-10000	0	-0.39	34	34
INCENP	0.009	0.002	-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	78	78
HDAC7	0.007	0.007	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.28	0.37	-9999	-0.89	60	60
SMAD4	0.011	0.003	-9999	-10000	0	0
ID2	-0.34	0.47	-9999	-1.1	78	78
AP1	-0.031	0.099	-9999	-0.36	32	32
ABCG2	-0.36	0.5	-9999	-1.1	82	82
HIF1A	-0.041	0.071	-9999	-10000	0	0
TFF3	-0.4	0.52	-9999	-1.1	95	95
GATA2	-0.039	0.15	-9999	-0.51	36	36
AKT1	-0.046	0.08	-9999	-10000	0	0
response to hypoxia	-0.064	0.084	-9999	-0.24	8	8
MCL1	-0.34	0.47	-9999	-1.1	78	78
NDRG1	-0.34	0.47	-9999	-1.1	78	78
SERPINE1	-0.34	0.47	-9999	-1.1	80	80
FECH	-0.34	0.47	-9999	-1.1	78	78
FURIN	-0.34	0.48	-9999	-1.1	79	79
NCOA2	0.008	0.036	-9999	-0.5	2	2
EP300	-0.047	0.12	-9999	-0.34	12	12
HMOX1	-0.34	0.47	-9999	-1.1	78	78
BHLHE40	-0.34	0.47	-9999	-1.1	78	78
BHLHE41	-0.35	0.48	-9999	-1.1	80	80
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.039	0.068	-9999	-0.39	3	3
ENG	-0.011	0.1	-9999	-0.57	4	4
JUN	0.006	0.037	-9999	-0.51	2	2
RORA	-0.34	0.47	-9999	-1.1	79	79
ABCB1	-0.12	0.24	-9999	-1.2	16	16
TFRC	-0.34	0.47	-9999	-1.1	78	78
CXCR4	-0.34	0.47	-9999	-1.1	78	78
TF	-0.4	0.52	-9999	-1.1	95	95
CITED2	-0.34	0.47	-9999	-1.1	78	78
HIF1A/ARNT	-0.39	0.55	-9999	-1.2	87	87
LDHA	-0.047	0.06	-9999	-0.46	1	1
ETS1	-0.34	0.47	-9999	-1.1	78	78
PGK1	-0.34	0.47	-9999	-1.1	78	78
NOS2	-0.36	0.49	-9999	-1.1	87	87
ITGB2	-0.34	0.48	-9999	-1.1	80	80
ALDOA	-0.34	0.47	-9999	-1.1	78	78
Cbp/p300/CITED2	-0.34	0.49	-9999	-1.1	69	69
FOS	-0.031	0.14	-9999	-0.51	30	30
HK2	-0.34	0.47	-9999	-1.1	79	79
SP1	0.015	0.014	-9999	-10000	0	0
GCK	-0.12	0.28	-9999	-1.2	15	15
HK1	-0.34	0.47	-9999	-1.1	78	78
NPM1	-0.34	0.47	-9999	-1.1	78	78
EGLN1	-0.34	0.47	-9999	-1.1	78	78
CREB1	0.016	0.001	-9999	-10000	0	0
PGM1	-0.34	0.47	-9999	-1.1	78	78
SMAD3	0.011	0.003	-9999	-10000	0	0
EDN1	-0.2	0.44	-9999	-1.2	63	63
IGFBP1	-0.37	0.49	-9999	-1.1	86	86
VEGFA	-0.26	0.36	-9999	-0.83	50	50
HIF1A/JAB1	-0.026	0.032	-9999	-10000	0	0
CP	-0.46	0.53	-9999	-1.1	108	108
CXCL12	-0.35	0.49	-9999	-1.1	82	82
COPS5	0.01	0.001	-9999	-10000	0	0
SMAD3/SMAD4	0	0.003	-9999	-10000	0	0
BNIP3	-0.34	0.47	-9999	-1.1	78	78
EGLN3	-0.4	0.53	-9999	-1.1	97	97
CA9	-0.5	0.52	-9999	-1.1	114	114
TERT	-0.4	0.52	-9999	-1.1	92	92
ENO1	-0.34	0.47	-9999	-1.1	78	78
PFKL	-0.34	0.47	-9999	-1.1	78	78
NCOA1	0.01	0	-9999	-10000	0	0
ADM	-0.34	0.47	-9999	-1.1	78	78
ARNT	-0.042	0.071	-9999	-10000	0	0
HNF4A	-0.11	0.22	-9999	-0.52	86	86
ADFP	-0.34	0.47	-9999	-1.1	82	82
SLC2A1	-0.34	0.42	-9999	-0.91	91	91
LEP	-0.36	0.49	-9999	-1.1	85	85
HIF1A/ARNT/Cbp/p300	-0.3	0.38	-9999	-0.89	72	72
EPO	-0.15	0.26	-9999	-0.78	4	4
CREBBP	-0.047	0.12	-9999	-0.35	11	11
HIF1A/ARNT/Cbp/p300/HDAC7	-0.32	0.4	-9999	-0.94	72	72
PFKFB3	-0.34	0.47	-9999	-1.1	74	74
NT5E	-0.35	0.48	-9999	-1.1	85	85

×

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	-0.018	0.065	-9999	-0.26	27	27
RGS9BP	-0.065	0.18	-9999	-0.5	57	57
mol:GTP	0	0	-9999	-10000	0	0
GRK1	-0.028	0.13	-9999	-0.52	25	25
mol:Na +	-0.16	0.18	-9999	-0.35	178	178
mol:ADP	-0.015	0.095	-9999	-0.37	26	26
GNAT2	0.007	0.027	-9999	-0.52	1	1
RGS9-1/Gbeta5/R9AP	-0.14	0.18	-9999	-0.33	163	163
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.002	0.022	-9999	-0.32	2	2
GRK7	0.005	0.027	-9999	-0.52	1	1
CNGB3	-0.09	0.2	-9999	-0.52	71	71
Cone Metarhodopsin II/X-Arrestin	-0.001	0.019	-9999	-0.38	1	1
mol:Ca2+	-0.16	0.19	-9999	-0.33	197	197
Cone PDE6	-0.12	0.15	-9999	-0.5	24	24
Cone Metarhodopsin II	-0.019	0.071	-9999	-0.28	26	26
Na + (4 Units)	-0.16	0.18	-9999	-0.33	197	197
GNAT2/GDP	-0.12	0.15	-9999	-0.48	26	26
GNB5	0.01	0	-9999	-10000	0	0
mol:GMP (4 units)	0.007	0.021	-9999	-0.28	2	2
Cone Transducin	-0.019	0.069	-9999	-0.27	27	27
SLC24A2	-0.039	0.15	-9999	-0.52	34	34
GNB3/GNGT2	-0.024	0.09	-9999	-0.36	26	26
GNB3	-0.016	0.11	-9999	-0.52	19	19
GNAT2/GTP	-0.001	0.019	-9999	-0.38	1	1
CNGA3	-0.16	0.25	-9999	-0.52	129	129
ARR3	0.001	0.027	-9999	-0.52	1	1
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.16	0.18	-9999	-0.35	178	178
mol:Pi	-0.14	0.17	-9999	-0.33	163	163
Cone CNG Channel	-0.13	0.15	-9999	-0.52	23	23
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.039	0.15	-9999	-0.52	34	34
RGS9	-0.16	0.24	-9999	-0.5	129	129
PDE6C	0.002	0.004	-9999	-10000	0	0
GNGT2	0.001	0.068	-9999	-0.5	7	7
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.001	0.027	-9999	-0.52	1	1

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.19	0.14	-9999	-0.36	70	70
NF kappa B1 p50/RelA/I kappa B alpha	-0.16	0.11	-9999	-0.46	20	20
alphaV/beta3 Integrin/Osteopontin/Src	-0.27	0.16	-9999	-0.36	293	293
AP1	-0.18	0.13	-9999	-0.45	45	45
ILK	-0.2	0.15	-9999	-0.54	20	20
bone resorption	-0.17	0.11	-9999	-0.44	24	24
PTK2B	0.007	0.036	-9999	-0.5	2	2
PYK2/p130Cas	-0.19	0.12	-9999	-0.49	23	23
ITGAV	0.011	0.003	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.004	0.036	-9999	-0.35	4	4
alphaV/beta3 Integrin/Osteopontin	-0.24	0.15	-9999	-0.32	298	298
MAP3K1	-0.2	0.15	-9999	-0.37	71	71
JUN	0.007	0.036	-9999	-0.5	2	2
MAPK3	-0.19	0.15	-9999	-0.39	70	70
MAPK1	-0.19	0.15	-9999	-0.39	70	70
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0.01	0	-9999	-10000	0	0
MAPK8	-0.18	0.14	-9999	-0.5	21	21
ITGB3	-0.022	0.13	-9999	-0.52	25	25
NFKBIA	-0.17	0.14	-9999	-0.38	70	70
FOS	-0.029	0.14	-9999	-0.5	30	30
CD44	0.005	0.051	-9999	-0.5	4	4
CHUK	0.01	0	-9999	-10000	0	0
PLAU	-0.18	0.18	-9999	-0.52	60	60
NF kappa B1 p50/RelA	-0.17	0.12	-9999	-0.48	20	20
BCAR1	0.009	0.026	-9999	-0.5	1	1
RELA	0.01	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.023	0.089	-9999	-0.37	25	25
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.21	0.15	-9999	-0.37	71	71
VAV3	-0.19	0.14	-9999	-0.52	24	24
MAP3K14	-0.21	0.15	-9999	-0.39	71	71
ROCK2	0.01	0	-9999	-10000	0	0
SPP1	-0.38	0.23	-9999	-0.52	293	293
RAC1	0.01	0	-9999	-10000	0	0
Rac1/GTP	-0.18	0.12	-9999	-0.47	24	24
MMP2	-0.14	0.13	-9999	-0.44	16	16

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.47	0.53	-10000	0	-1.2	98	98
STAT6 (cleaved dimer)	-0.51	0.5	-10000	0	-1.1	128	128
IGHG1	-0.15	0.17	-10000	0	-0.37	23	23
IGHG3	-0.46	0.51	-10000	0	-1.1	126	126
AKT1	-0.18	0.24	-10000	0	-0.77	9	9
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.13	0.19	-10000	0	-0.89	6	6
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.2	0.25	-10000	0	-0.81	10	10
THY1	-0.48	0.54	-10000	0	-1.2	100	100
MYB	0.003	0.058	-10000	0	-0.51	5	5
HMGA1	-0.052	0.17	-10000	0	-0.52	46	46
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.25	0.28	-10000	0	-0.62	79	79
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.2	0.25	-10000	0	-0.88	9	9
SP1	0.016	0.005	-10000	0	-10000	0	0
INPP5D	0.006	0.045	-10000	0	-0.5	3	3
SOCS5	0.021	0.014	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.49	0.5	-10000	0	-1.1	122	122
SOCS1	-0.28	0.33	-10000	0	-0.75	88	88
SOCS3	-0.2	0.25	-10000	0	-0.87	10	10
FCER2	-0.36	0.42	-10000	0	-1	69	69
PARP14	0.01	0.003	-10000	0	-10000	0	0
CCL17	-0.53	0.61	-10000	0	-1.4	107	107
GRB2	0.01	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.16	0.2	-10000	0	-0.73	7	7
T cell proliferation	-0.46	0.54	-10000	0	-1.2	100	100
IL4R/JAK1	-0.47	0.53	-10000	0	-1.2	100	100
EGR2	-0.49	0.57	-10000	0	-1.3	99	99
JAK2	-0.013	0.04	-10000	0	-0.54	1	1
JAK3	0.015	0.004	-10000	0	-10000	0	0
PIK3R1	0.01	0	-10000	0	-10000	0	0
JAK1	0.006	0.011	-10000	0	-10000	0	0
COL1A2	-0.14	0.2	-10000	0	-0.74	12	12
CCL26	-0.49	0.55	-10000	0	-1.3	101	101
IL4R	-0.5	0.57	-10000	0	-1.3	100	100
PTPN6	0.021	0.013	-10000	0	-10000	0	0
IL13RA2	-0.52	0.59	-10000	0	-1.3	112	112
IL13RA1	-0.011	0.03	-10000	0	-10000	0	0
IRF4	-0.11	0.24	-10000	0	-0.83	26	26
ARG1	-0.13	0.19	-10000	0	-0.7	19	19
CBL	-0.23	0.26	-10000	0	-0.6	64	64
GTF3A	0.005	0.032	-10000	0	-0.51	1	1
PIK3CA	0.01	0	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.015	0.047	-10000	0	-0.4	1	1
IRF4/BCL6	-0.12	0.2	-10000	0	-0.78	25	25
CD40LG	-0.009	0.11	-10000	0	-0.5	19	19
MAPK14	-0.22	0.27	-10000	0	-0.61	59	59
mitosis	-0.18	0.23	-10000	0	-0.72	9	9
STAT6	-0.56	0.64	-10000	0	-1.4	120	120
SPI1	-0.016	0.12	-10000	0	-0.5	22	22
RPS6KB1	-0.16	0.22	-10000	0	-0.74	7	7
STAT6 (dimer)	-0.56	0.64	-10000	0	-1.4	120	120
STAT6 (dimer)/PARP14	-0.51	0.58	-10000	0	-1.3	108	108
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	23	23
FRAP1	-0.18	0.24	-10000	0	-0.77	9	9
LTA	-0.48	0.53	-10000	0	-1.2	101	101
FES	0.009	0.026	-10000	0	-0.5	1	1
T-helper 1 cell differentiation	0.54	0.61	1.3	120	-10000	0	120
CCL11	-0.48	0.54	-10000	0	-1.2	104	104
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.19	0.24	-10000	0	-0.82	9	9
IL2RG	0.009	0.051	-10000	0	-0.49	4	4
IL10	-0.48	0.54	-10000	0	-1.2	103	103
IRS1	0.009	0.026	-10000	0	-0.5	1	1
IRS2	0.009	0.026	-10000	0	-0.5	1	1
IL4	-0.1	0.12	-10000	0	-10000	0	0
IL5	-0.48	0.53	-10000	0	-1.2	98	98
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.38	0.4	-10000	0	-0.92	99	99
COL1A1	-0.23	0.24	-10000	0	-0.64	51	51
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.48	0.55	-10000	0	-1.3	97	97
IL2R gamma/JAK3	0.014	0.037	-10000	0	-0.34	4	4
TFF3	-0.53	0.57	-10000	0	-1.3	111	111
ALOX15	-0.81	0.73	-10000	0	-1.4	215	215
MYBL1	-0.001	0.075	-10000	0	-0.52	8	8
T-helper 2 cell differentiation	-0.38	0.41	-10000	0	-0.93	101	101
SHC1	0.01	0	-10000	0	-10000	0	0
CEBPB	0.012	0.006	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.19	0.24	-10000	0	-0.86	8	8
mol:PI-3-4-5-P3	-0.18	0.24	-10000	0	-0.77	9	9
PI3K	-0.19	0.25	-10000	0	-0.84	9	9
DOK2	-0.034	0.14	-10000	0	-0.5	34	34
ETS1	0.02	0.013	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.14	0.19	-10000	0	-0.68	7	7
ITGB3	-0.48	0.54	-10000	0	-1.3	99	99
PIGR	-0.63	0.69	-10000	0	-1.5	136	136
IGHE	0.034	0.042	-10000	0	-10000	0	0
MAPKKK cascade	-0.14	0.19	-10000	0	-0.67	7	7
BCL6	0.01	0.002	-10000	0	-10000	0	0
OPRM1	-0.48	0.53	-10000	0	-1.2	99	99
RETNLB	-0.48	0.54	-10000	0	-1.3	95	95
SELP	-0.59	0.67	-10000	0	-1.5	122	122
AICDA	-0.5	0.55	-10000	0	-1.2	109	109

×

amb2 Integrin signaling

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
alphaM/beta2 Integrin/proMMP-2	-0.024	0.097	-9999	-0.43	19	19
alphaM/beta2 Integrin/GPIbA	-0.028	0.11	-9999	-0.42	24	24
alphaM/beta2 Integrin/proMMP-9	-0.076	0.15	-9999	-0.34	85	85
PLAUR	0.01	0	-9999	-10000	0	0
HMGB1	0.005	0.011	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.024	0.1	-9999	-0.45	18	18
AGER	-0.47	0.14	-9999	-0.51	363	363
RAP1A	0.01	0	-9999	-10000	0	0
SELPLG	-0.007	0.091	-9999	-0.5	13	13
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.3	0.16	-9999	-0.51	104	104
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.082	0.2	-9999	-0.52	68	68
CYR61	-0.019	0.12	-9999	-0.5	22	22
TLN1	0.009	0.026	-9999	-0.5	1	1
Rap1/GTP	-0.082	0.14	-9999	-0.43	35	35
RHOA	0.01	0	-9999	-10000	0	0
P-selectin oligomer	-0.099	0.21	-9999	-0.5	84	84
MYH2	-0.15	0.2	-9999	-0.47	79	79
MST1R	0.006	0.045	-9999	-0.51	3	3
leukocyte activation during inflammatory response	-0.045	0.12	-9999	-0.31	55	55
APOB	-0.041	0.15	-9999	-0.51	38	38
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	0.008	0.027	-9999	-0.52	1	1
JAM3	0.003	0.057	-9999	-0.5	5	5
GP1BA	0	0.068	-9999	-0.5	7	7
alphaM/beta2 Integrin/CTGF	-0.037	0.12	-9999	-0.4	34	34
alphaM/beta2 Integrin	-0.085	0.18	-9999	-0.44	50	50
JAM3 homodimer	0.003	0.057	-9999	-0.5	5	5
ICAM2	0.005	0.051	-9999	-0.5	4	4
ICAM1	0.002	0.063	-9999	-0.5	6	6
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.084	0.18	-9999	-0.43	50	50
cell adhesion	-0.028	0.11	-9999	-0.42	24	24
NFKB1	-0.31	0.23	-9999	-0.63	104	104
THY1	-0.006	0.091	-9999	-0.52	12	12
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.032	0.094	-9999	-0.31	40	40
alphaM/beta2 Integrin/LRP/tPA	-0.056	0.14	-9999	-0.35	58	58
IL6	-0.36	0.33	-9999	-0.85	109	109
ITGB2	-0.007	0.079	-9999	-0.52	9	9
elevation of cytosolic calcium ion concentration	-0.068	0.13	-9999	-0.3	89	89
alphaM/beta2 Integrin/JAM2/JAM3	-0.049	0.14	-9999	-0.47	28	28
JAM2	-0.042	0.16	-9999	-0.5	40	40
alphaM/beta2 Integrin/ICAM1	-0.03	0.11	-9999	-0.49	15	15
alphaM/beta2 Integrin/uPA/Plg	-0.077	0.14	-9999	-0.31	96	96
RhoA/GTP	-0.1	0.19	-9999	-0.47	50	50
positive regulation of phagocytosis	-0.078	0.16	-9999	-0.65	22	22
Ron/MSP	-0.015	0.072	-9999	-0.37	16	16
alphaM/beta2 Integrin/uPAR/uPA	-0.068	0.13	-9999	-0.3	89	89
alphaM/beta2 Integrin/uPAR	-0.023	0.096	-9999	-0.44	18	18
PLAU	-0.087	0.2	-9999	-0.52	72	72
PLAT	-0.056	0.17	-9999	-0.52	49	49
actin filament polymerization	-0.14	0.19	-9999	-0.44	79	79
MST1	-0.008	0.094	-9999	-0.52	13	13
alphaM/beta2 Integrin/lipoprotein(a)	-0.045	0.12	-9999	-0.31	55	55
TNF	-0.29	0.25	-9999	-0.64	104	104
RAP1B	0.01	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.079	0.15	-9999	-0.34	89	89
fibrinolysis	-0.077	0.14	-9999	-0.31	96	96
HCK	-0.011	0.1	-9999	-0.5	16	16
dendritic cell antigen processing and presentation	-0.084	0.18	-9999	-0.43	50	50
VTN	-0.083	0.2	-9999	-0.5	71	71
alphaM/beta2 Integrin/CYR61	-0.04	0.12	-9999	-0.39	37	37
LPA	0	0.037	-9999	-0.52	2	2
LRP1	0.005	0.051	-9999	-0.5	4	4
cell migration	-0.067	0.13	-9999	-0.3	85	85
FN1	0.005	0.051	-9999	-0.5	4	4
alphaM/beta2 Integrin/Thy1	-0.032	0.11	-9999	-0.39	30	30
MPO	-0.001	0.073	-9999	-0.5	8	8
KNG1	-0.033	0.14	-9999	-0.52	28	28
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.089	0.18	-9999	-0.44	48	48
ELA2	0	0	-9999	-10000	0	0
PLG	-0.01	0.078	-9999	-0.52	9	9
CTGF	-0.015	0.11	-9999	-0.5	19	19
alphaM/beta2 Integrin/Hck	-0.034	0.14	-9999	-0.54	23	23
ITGAM	-0.017	0.11	-9999	-0.51	17	17
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.083	0.19	-9999	-0.36	90	90
HP	-0.13	0.23	-9999	-0.5	107	107
leukocyte adhesion	-0.28	0.19	-9999	-0.48	133	133
SELP	-0.099	0.21	-9999	-0.5	84	84

×

BMP receptor signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.082	0.14	-9999	-0.52	15	15
SMAD6-7/SMURF1	-0.039	0.1	-9999	-0.3	52	52
NOG	-0.031	0.14	-9999	-0.51	31	31
SMAD9	-0.11	0.19	-9999	-0.48	79	79
SMAD4	0.01	0	-9999	-10000	0	0
SMAD5	-0.027	0.11	-9999	-0.35	19	19
BMP7/USAG1	-0.28	0.2	-9999	-0.39	279	279
SMAD5/SKI	-0.02	0.11	-9999	-0.44	6	6
SMAD1	0.022	0.029	-9999	-10000	0	0
BMP2	-0.059	0.18	-9999	-0.5	53	53
SMAD1/SMAD1/SMAD4	-0.026	0.067	-9999	-0.41	1	1
BMPR1A	0.01	0	-9999	-10000	0	0
BMPR1B	-0.045	0.16	-9999	-0.5	42	42
BMPR1A-1B/BAMBI	-0.044	0.11	-9999	-0.31	55	55
AHSG	-0.038	0.14	-9999	-0.52	32	32
CER1	-0.003	0.052	-9999	-0.52	4	4
BMP2-4/CER1	-0.051	0.12	-9999	-0.32	62	62
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.018	0.12	-9999	-0.39	16	16
BMP2-4 (homodimer)	-0.057	0.14	-9999	-0.38	60	60
RGMB	0.01	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.068	0.13	-9999	-0.46	17	17
RGMA	-0.001	0.074	-9999	-0.51	8	8
SMURF1	0.01	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.025	0.11	-9999	-0.36	17	17
BMP2-4/USAG1	-0.24	0.18	-9999	-0.34	273	273
SMAD6/SMURF1/SMAD5	-0.02	0.11	-9999	-0.4	8	8
SOSTDC1	-0.33	0.24	-9999	-0.5	258	258
BMP7/BMPR2/BMPR1A-1B	-0.065	0.12	-9999	-0.28	92	92
SKI	0.01	0	-9999	-10000	0	0
BMP6 (homodimer)	-0.07	0.18	-9999	-0.5	61	61
HFE2	-0.005	0.074	-9999	-0.52	8	8
ZFYVE16	0.01	0	-9999	-10000	0	0
MAP3K7	0.01	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.059	0.13	-9999	-0.33	71	71
SMAD5/SMAD5/SMAD4	-0.02	0.11	-9999	-0.42	7	7
MAPK1	0.01	0	-9999	-10000	0	0
TAK1/TAB family	-0.04	0.081	-9999	-0.35	10	10
BMP7 (homodimer)	-0.064	0.18	-9999	-0.51	56	56
NUP214	0.01	0	-9999	-10000	0	0
BMP6/FETUA	-0.085	0.16	-9999	-0.38	89	89
SMAD1/SKI	0.027	0.028	-9999	-10000	0	0
SMAD6	-0.058	0.17	-9999	-0.5	52	52
CTDSP2	0.01	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.073	0.14	-9999	-0.33	87	87
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.37	0.24	-9999	-0.52	281	281
BMPR2 (homodimer)	0.01	0	-9999	-10000	0	0
GADD34/PP1CA	-0.001	0.021	-9999	-0.29	2	2
BMPR1A-1B (homodimer)	-0.038	0.11	-9999	-0.36	42	42
CHRDL1	-0.16	0.24	-9999	-0.5	134	134
ENDOFIN/SMAD1	0.027	0.028	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.03	0.076	-9999	-0.46	1	1
SMAD6/SMURF1	0.01	0	-9999	-10000	0	0
BAMBI	-0.012	0.1	-9999	-0.52	16	16
SMURF2	0.01	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.15	0.2	-9999	-0.36	158	158
BMP2-4/GREM1	-0.26	0.18	-9999	-0.35	299	299
SMAD7	0.009	0.026	-9999	-0.5	1	1
SMAD8A/SMAD8A/SMAD4	-0.082	0.19	-9999	-0.45	78	78
SMAD1/SMAD6	0.027	0.028	-9999	-10000	0	0
TAK1/SMAD6	0	0	-9999	-10000	0	0
BMP7	-0.064	0.18	-9999	-0.51	56	56
BMP6	-0.07	0.18	-9999	-0.5	61	61
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.019	0.11	-9999	-0.34	17	17
PPM1A	0.01	0	-9999	-10000	0	0
SMAD1/SMURF2	0.027	0.028	-9999	-10000	0	0
SMAD7/SMURF1	-0.001	0.018	-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	0.007	0.036	-9999	-0.5	2	2
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.039	0.13	-9999	-0.39	27	27
CHRD	-0.01	0.1	-9999	-0.52	15	15
BMPR2	0.01	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.031	0.12	-9999	-0.39	17	17
BMP4	-0.005	0.085	-9999	-0.5	11	11
FST	-0.037	0.15	-9999	-0.51	35	35
BMP2-4/NOG	-0.071	0.15	-9999	-0.34	81	81
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.06	0.11	-9999	-0.5	6	6

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.008	0.027	-9999	-0.52	1	1
LAT2	-0.093	0.2	-9999	-0.48	61	61
AP1	-0.13	0.21	-9999	-0.5	76	76
mol:PIP3	-0.098	0.22	-9999	-0.51	68	68
IKBKB	-0.042	0.12	-9999	-0.27	62	62
AKT1	-0.064	0.16	-9999	-0.39	59	59
IKBKG	-0.042	0.12	-9999	-0.27	63	63
MS4A2	-0.11	0.22	-9999	-0.5	93	93
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.009	0.002	-9999	-10000	0	0
MAP3K1	-0.065	0.18	-9999	-0.4	68	68
mol:Ca2+	-0.069	0.17	-9999	-0.37	68	68
LYN	0.008	0.005	-9999	-10000	0	0
CBLB	-0.087	0.19	-9999	-0.45	61	61
SHC1	0.01	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.024	0.076	-9999	-0.26	36	36
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0.006	0.045	-9999	-0.5	3	3
PLD2	-0.097	0.19	-9999	-0.47	58	58
PTPN13	-0.11	0.22	-9999	-0.51	75	75
PTPN11	0.007	0.008	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.044	0.15	-9999	-0.32	59	59
SYK	0.004	0.047	-9999	-0.53	3	3
GRB2	0.009	0.001	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.14	0.2	-9999	-0.52	68	68
LAT	-0.088	0.19	-9999	-0.46	59	59
PAK2	-0.08	0.2	-9999	-0.46	68	68
NFATC2	-0.067	0.15	-9999	-0.78	14	14
HRAS	-0.094	0.23	-9999	-0.51	68	68
GAB2	0.005	0.051	-9999	-0.5	4	4
PLA2G1B	-0.001	0.031	-9999	-10000	0	0
Fc epsilon R1	-0.15	0.22	-9999	-0.4	147	147
Antigen/IgE/Fc epsilon R1	-0.14	0.2	-9999	-0.37	147	147
mol:GDP	-0.11	0.24	-9999	-0.55	70	70
JUN	0.007	0.036	-9999	-0.5	2	2
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.009	0.002	-9999	-10000	0	0
FOS	-0.029	0.14	-9999	-0.5	30	30
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.12	0.18	-9999	-0.39	97	97
CHUK	-0.042	0.12	-9999	-0.27	63	63
KLRG1	-0.082	0.18	-9999	-0.43	59	59
VAV1	-0.09	0.2	-9999	-0.47	61	61
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.087	0.19	-9999	-0.45	60	60
negative regulation of mast cell degranulation	-0.073	0.17	-9999	-0.4	59	59
BTK	-0.14	0.25	-9999	-0.59	70	70
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.11	0.22	-9999	-0.58	58	58
GAB2/PI3K/SHP2	-0.1	0.16	-9999	-0.42	59	59
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.098	0.2	-9999	-0.5	59	59
RAF1	0.021	0.023	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.12	0.19	-9999	-0.5	58	58
FCER1G	-0.002	0.087	-9999	-0.51	11	11
FCER1A	-0.13	0.23	-9999	-0.51	105	105
Antigen/IgE/Fc epsilon R1/Fyn	-0.13	0.18	-9999	-0.5	59	59
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	-0.011	0.061	-9999	-10000	0	0
DUSP1	-0.037	0.15	-9999	-0.5	36	36
NF-kappa-B/RelA	-0.043	0.061	-9999	-0.23	5	5
actin cytoskeleton reorganization	-0.095	0.2	-9999	-0.48	61	61
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.11	0.18	-9999	-0.45	66	66
FER	-0.087	0.19	-9999	-0.45	60	60
RELA	0.01	0	-9999	-10000	0	0
ITK	-0.037	0.083	-9999	-0.52	9	9
SOS1	0.01	0	-9999	-10000	0	0
PLCG1	-0.1	0.24	-9999	-0.55	68	68
cytokine secretion	-0.031	0.044	-9999	-10000	0	0
SPHK1	-0.089	0.19	-9999	-0.45	62	62
PTK2	-0.1	0.21	-9999	-0.5	61	61
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.14	0.22	-9999	-0.55	68	68
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.093	0.22	-9999	-0.49	69	69
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	-0.092	0.15	-9999	-0.38	59	59
MAP2K4	0.011	0.011	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.13	0.19	-9999	-0.4	108	108
mol:Choline	-0.095	0.18	-9999	-0.46	58	58
SHC/Grb2/SOS1	-0.1	0.16	-9999	-0.42	59	59
FYN	0.009	0.026	-9999	-0.5	1	1
DOK1	0.01	0	-9999	-10000	0	0
PXN	-0.086	0.19	-9999	-0.46	59	59
HCLS1	-0.089	0.19	-9999	-0.46	60	60
PRKCB	-0.07	0.17	-9999	-0.37	69	69
FCGR2B	0.01	0	-9999	-10000	0	0
IGHE	-0.002	0.006	-9999	-10000	0	0
KLRG1/SHIP	-0.075	0.17	-9999	-0.41	59	59
LCP2	0.007	0.037	-9999	-0.5	2	2
PLA2G4A	-0.13	0.22	-9999	-0.49	78	78
RASA1	0.01	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.095	0.18	-9999	-0.46	58	58
IKK complex	-0.02	0.098	-9999	-0.23	18	18
WIPF1	0.01	0	-9999	-10000	0	0

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	-0.091	0.32	-9999	-1	38	38
MKNK1	0.01	0	-9999	-10000	0	0
MAPK14	-0.027	0.12	-9999	-0.43	6	6
ATF2/c-Jun	-0.011	0.11	-9999	-0.52	7	7
MAPK11	-0.032	0.13	-9999	-0.49	9	9
MITF	-0.031	0.16	-9999	-0.36	65	65
MAPKAPK5	-0.027	0.15	-9999	-0.34	65	65
KRT8	-0.029	0.15	-9999	-0.35	65	65
MAPKAPK3	0.01	0	-9999	-10000	0	0
MAPKAPK2	0.01	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.044	0.18	-9999	-0.43	65	65
CEBPB	-0.027	0.15	-9999	-0.34	65	65
SLC9A1	-0.027	0.15	-9999	-0.34	65	65
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.022	0.14	-9999	-0.34	65	65
p38alpha-beta/MNK1	-0.026	0.14	-9999	-0.52	9	9
JUN	-0.011	0.11	-9999	-0.51	7	7
PPARGC1A	-0.11	0.22	-9999	-0.45	67	67
USF1	-0.027	0.15	-9999	-0.34	65	65
RAB5/GDP/GDI1	-0.042	0.094	-9999	-0.37	9	9
NOS2	-0.081	0.3	-9999	-1	31	31
DDIT3	-0.028	0.15	-9999	-0.34	65	65
RAB5A	0.01	0	-9999	-10000	0	0
HSPB1	-0.016	0.12	-9999	-0.45	10	10
p38alpha-beta/HBP1	-0.026	0.14	-9999	-0.52	9	9
CREB1	-0.028	0.16	-9999	-0.37	65	65
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	-0.017	0.13	-9999	-0.5	7	7
RPS6KA4	-0.027	0.15	-9999	-0.34	65	65
PLA2G4A	-0.063	0.16	-9999	-0.53	15	15
GDI1	-0.027	0.15	-9999	-0.34	65	65
TP53	-0.037	0.18	-9999	-0.42	65	65
RPS6KA5	-0.029	0.15	-9999	-0.35	66	66
ESR1	-0.045	0.18	-9999	-0.39	66	66
HBP1	0.01	0	-9999	-10000	0	0
MEF2C	-0.027	0.15	-9999	-0.34	65	65
MEF2A	-0.027	0.15	-9999	-0.34	65	65
EIF4EBP1	-0.029	0.16	-9999	-0.37	65	65
KRT19	-0.03	0.15	-9999	-0.34	65	65
ELK4	-0.027	0.15	-9999	-0.34	65	65
ATF6	-0.027	0.15	-9999	-0.34	65	65
ATF1	-0.028	0.16	-9999	-0.37	65	65
p38alpha-beta/MAPKAPK2	-0.026	0.14	-9999	-0.52	9	9
p38alpha-beta/MAPKAPK3	-0.026	0.14	-9999	-0.52	9	9

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.035	0.043	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.088	0.12	-9999	-0.36	25	25
JUN	-0.056	0.12	-9999	-0.35	22	22
HRAS	0.01	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.13	0.16	-9999	-0.42	41	41
RAP1A	0.01	0	-9999	-10000	0	0
FRS2	0.007	0.038	-9999	-0.52	2	2
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.13	0.16	-9999	-0.54	23	23
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	-0.089	0.13	-9999	-0.28	127	127
RHOA	0.01	0	-9999	-10000	0	0
RAP1A/GTP	-0.11	0.14	-9999	-0.48	23	23
GRB7	0.003	0.058	-9999	-0.51	5	5
RET51/GFRalpha1/GDNF	-0.13	0.16	-9999	-0.54	23	23
MAPKKK cascade	-0.1	0.13	-9999	-0.44	26	26
BCAR1	0.009	0.026	-9999	-0.5	1	1
RET9/GFRalpha1/GDNF/IRS1	-0.09	0.13	-9999	-0.28	127	127
lamellipodium assembly	-0.085	0.11	-9999	-0.34	25	25
RET51/GFRalpha1/GDNF/SHC	-0.13	0.16	-9999	-0.32	113	113
PIK3CA	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.089	0.13	-9999	-0.28	127	127
RET9/GFRalpha1/GDNF/Shank3	-0.094	0.14	-9999	-0.29	128	128
MAPK3	-0.084	0.15	-9999	-0.45	23	23
DOK1	0.01	0	-9999	-10000	0	0
DOK6	-0.037	0.15	-9999	-0.5	36	36
PXN	0.01	0	-9999	-10000	0	0
neurite development	-0.088	0.15	-9999	-0.38	46	46
DOK5	-0.071	0.19	-9999	-0.52	60	60
GFRA1	-0.15	0.24	-9999	-0.5	120	120
MAPK8	-0.064	0.12	-9999	-0.35	21	21
HRAS/GTP	-0.11	0.14	-9999	-0.47	23	23
tube development	-0.086	0.13	-9999	-0.38	17	17
MAPK1	-0.084	0.15	-9999	-0.45	23	23
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.058	0.12	-9999	-0.23	119	119
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	-0.14	0.18	-9999	-0.52	46	46
SHC1	0.01	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.13	0.16	-9999	-0.32	113	113
RET51/GFRalpha1/GDNF/Dok5	-0.17	0.19	-9999	-0.34	158	158
PRKCA	0.007	0.036	-9999	-0.5	2	2
HRAS/GDP	0	0	-9999	-10000	0	0
CREB1	-0.075	0.14	-9999	-0.28	119	119
PIK3R1	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.058	0.12	-9999	-0.24	119	119
RET51/GFRalpha1/GDNF/Grb7	-0.13	0.16	-9999	-0.3	167	167
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.067	0.19	-9999	-0.52	57	57
DOK4	0.01	0	-9999	-10000	0	0
JNK cascade	-0.055	0.12	-9999	-0.34	22	22
RET9/GFRalpha1/GDNF/FRS2	-0.09	0.13	-9999	-0.28	129	129
SHANK3	0.001	0.068	-9999	-0.5	7	7
RASA1	0.01	0	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.058	0.12	-9999	-0.23	119	119
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.076	0.13	-9999	-0.37	22	22
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.075	0.13	-9999	-0.37	22	22
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.077	0.14	-9999	-0.42	22	22
PI3K	-0.095	0.19	-9999	-0.52	25	25
SOS1	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.086	0.13	-9999	-0.38	17	17
GRB10	0.01	0	-9999	-10000	0	0
activation of MAPKK activity	-0.07	0.12	-9999	-0.34	22	22
RET51/GFRalpha1/GDNF/FRS2	-0.13	0.16	-9999	-0.32	115	115
GAB1	0.009	0.026	-9999	-0.5	1	1
IRS1	0.009	0.026	-9999	-0.5	1	1
IRS2	0.009	0.026	-9999	-0.5	1	1
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.078	0.14	-9999	-0.43	23	23
RET51/GFRalpha1/GDNF/PKC alpha	-0.13	0.16	-9999	-0.55	23	23
GRB2	0.01	0	-9999	-10000	0	0
PRKACA	0.01	0	-9999	-10000	0	0
GDNF	-0.008	0.083	-9999	-0.52	10	10
RAC1	0.01	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.13	0.16	-9999	-0.37	66	66
Rac1/GTP	-0.1	0.13	-9999	-0.4	25	25
RET9/GFRalpha1/GDNF	-0.1	0.15	-9999	-0.31	127	127
GFRalpha1/GDNF	-0.12	0.17	-9999	-0.37	127	127

×

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	-0.2	0.32	-10000	0	-0.83	39	39
PCK1	-0.17	0.23	-10000	0	-0.64	37	37
HNF4A	-0.39	0.49	-10000	0	-1	115	115
KCNJ11	-0.18	0.33	-10000	0	-0.9	36	36
AKT1	-0.07	0.14	-10000	0	-0.41	5	5
response to starvation	-0.027	0.046	-10000	0	-10000	0	0
DLK1	-0.2	0.32	-10000	0	-0.88	35	35
NKX2-1	-0.13	0.4	-10000	0	-1.4	32	32
ACADM	-0.2	0.32	-10000	0	-0.84	38	38
TAT	-0.16	0.22	-10000	0	-0.7	18	18
CEBPB	0.009	0.005	-10000	0	-10000	0	0
CEBPA	-0.021	0.12	-10000	0	-0.5	23	23
TTR	-0.2	0.25	-10000	0	-0.71	48	48
PKLR	-0.21	0.32	-10000	0	-0.88	37	37
APOA1	-0.49	0.63	-10000	0	-1.3	132	132
CPT1C	-0.21	0.32	-10000	0	-0.86	39	39
ALAS1	-0.07	0.16	-10000	0	-10000	0	0
TFRC	-0.16	0.27	-10000	0	-0.81	22	22
FOXF1	-0.061	0.18	0.22	2	-0.48	57	59
NF1	0.016	0	-10000	0	-10000	0	0
HNF1A (dimer)	-0.1	0.23	-10000	0	-0.58	72	72
CPT1A	-0.2	0.32	-10000	0	-0.85	36	36
HMGCS1	-0.2	0.32	-10000	0	-0.83	39	39
NR3C1	0.005	0.031	-10000	0	-10000	0	0
CPT1B	-0.21	0.32	-10000	0	-0.83	42	42
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0	0.025	-10000	0	-10000	0	0
GCK	-0.22	0.34	-10000	0	-0.87	49	49
CREB1	0.005	0.021	-10000	0	-10000	0	0
IGFBP1	-0.12	0.2	-10000	0	-0.56	25	25
PDX1	-0.16	0.26	-10000	0	-0.64	57	57
UCP2	-0.2	0.32	-10000	0	-0.83	39	39
ALDOB	-0.19	0.34	-10000	0	-0.84	49	49
AFP	-0.074	0.14	-10000	0	-0.53	16	16
BDH1	-0.21	0.32	-10000	0	-0.85	36	36
HADH	-0.17	0.31	-10000	0	-0.85	31	31
F2	-0.31	0.43	-10000	0	-1	62	62
HNF1A	-0.1	0.23	-10000	0	-0.58	72	72
G6PC	-0.082	0.16	-10000	0	-0.59	14	14
SLC2A2	-0.14	0.24	-10000	0	-0.68	21	21
INS	0	0.028	-10000	0	-10000	0	0
FOXA1	-0.014	0.11	0.27	4	-0.55	10	14
FOXA3	-0.17	0.27	-10000	0	-0.58	111	111
FOXA2	-0.2	0.36	-10000	0	-0.91	41	41
ABCC8	-0.22	0.38	-10000	0	-0.92	60	60
ALB	-0.085	0.16	-10000	0	-0.46	33	33

×

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	-0.021	0.12	-10000	0	-0.47	26	26
CDKN2C	0.022	0.034	-10000	0	-0.46	1	1
CDKN2A	-0.15	0.25	-10000	0	-0.54	115	115
CCND2	0.04	0.064	0.2	26	-0.12	5	31
RB1	-0.044	0.066	-10000	0	-0.2	27	27
CDK4	0.047	0.069	0.2	27	-10000	0	27
CDK6	0.045	0.068	0.21	26	-10000	0	26
G1/S progression	0.035	0.072	0.2	27	-10000	0	27

×

TCGA08_p53

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
CDKN2A	-0.1	0.18	-10000	0	-0.38	115	115
TP53	-0.027	0.045	0.18	1	-10000	0	1
Senescence	-0.027	0.045	0.18	1	-10000	0	1
Apoptosis	-0.027	0.045	0.18	1	-10000	0	1
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.052	0.089	0.19	114	-0.34	2	116
MDM4	0.01	0	-10000	0	-10000	0	0

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.01	0	-9999	-10000	0	0
GNAT1/GTP	-0.008	0.053	-9999	-0.38	8	8
Metarhodopsin II/Arrestin	-0.001	0.016	-9999	-0.32	1	1
PDE6G/GNAT1/GTP	-0.011	0.064	-9999	-0.36	12	12
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	-0.008	0.074	-9999	-0.52	8	8
GRK1	-0.028	0.13	-9999	-0.52	25	25
CNG Channel	-0.11	0.15	-9999	-0.5	30	30
mol:Na +	-0.12	0.15	-9999	-0.49	32	32
mol:ADP	-0.028	0.13	-9999	-0.52	25	25
RGS9-1/Gbeta5/R9AP	-0.14	0.18	-9999	-0.33	163	163
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.13	0.16	-9999	-0.51	32	32
CNGB1	-0.088	0.2	-9999	-0.52	73	73
RDH5	-0.001	0.075	-9999	-0.52	8	8
SAG	0.001	0.027	-9999	-0.52	1	1
mol:Ca2+	-0.098	0.16	-9999	-0.47	32	32
Na + (4 Units)	-0.11	0.14	-9999	-0.46	32	32
RGS9	-0.16	0.24	-9999	-0.5	129	129
GNB1/GNGT1	-0.075	0.15	-9999	-0.37	80	80
GNAT1/GDP	-0.12	0.15	-9999	-0.5	26	26
GUCY2D	0	0.069	-9999	-0.51	7	7
GNGT1	-0.1	0.21	-9999	-0.52	80	80
GUCY2F	0.001	0.027	-9999	-0.52	1	1
GNB5	0.01	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.014	0.098	-9999	-0.33	13	13
mol:11-cis-retinal	-0.001	0.075	-9999	-0.52	8	8
mol:cGMP	-0.054	0.11	-9999	-0.52	3	3
GNB1	0.01	0	-9999	-10000	0	0
Rhodopsin	-0.008	0.053	-9999	-0.37	8	8
SLC24A1	0.01	0	-9999	-10000	0	0
CNGA1	-0.068	0.19	-9999	-0.52	58	58
Metarhodopsin II	-0.018	0.07	-9999	-0.29	25	25
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.057	0.12	-9999	-0.29	71	71
RGS9BP	-0.065	0.18	-9999	-0.5	57	57
Metarhodopsin II/Transducin	-0.022	0.063	-9999	-0.23	2	2
GCAP Family/Ca ++	-0.053	0.12	-9999	-0.29	71	71
PDE6A/B	-0.033	0.1	-9999	-0.36	37	37
mol:Pi	-0.14	0.17	-9999	-0.33	163	163
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.063	0.12	-9999	-0.29	86	86
PDE6B	0.002	0.063	-9999	-0.5	6	6
PDE6A	-0.031	0.14	-9999	-0.5	31	31
PDE6G	0.002	0.063	-9999	-0.51	6	6
RHO	0.004	0.005	-9999	-10000	0	0
PDE6	-0.13	0.17	-9999	-0.49	47	47
GUCA1A	-0.085	0.2	-9999	-0.52	69	69
GC2/GCAP Family	-0.054	0.12	-9999	-0.3	52	52
GUCA1C	0	0.001	-9999	-10000	0	0
GUCA1B	0.003	0.058	-9999	-0.51	5	5

×

LPA4-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
ADCY4	-0.003	0.078	-9999	-0.31	23	23
ADCY5	-0.035	0.12	-9999	-0.31	61	61
ADCY6	0.012	0.035	-9999	-0.3	5	5
ADCY7	0.011	0.039	-9999	-0.3	6	6
ADCY1	0.006	0.055	-9999	-0.3	12	12
ADCY2	-0.02	0.1	-9999	-0.31	43	43
ADCY3	0.013	0.032	-9999	-0.3	4	4
ADCY8	-0.12	0.15	-9999	-0.3	164	164
PRKCE	0.005	0.037	-9999	-0.36	4	4
ADCY9	0.005	0.059	-9999	-0.3	14	14
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.064	0.1	-9999	-0.35	24	24

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.03	0.085	0.31	7	-10000	0	7
SMARCC2	0.011	0.006	-10000	0	-10000	0	0
SMARCC1	0.011	0.006	-10000	0	-10000	0	0
TBX21	-0.11	0.22	-10000	0	-0.62	42	42
SUMO2	0.009	0.005	-10000	0	-10000	0	0
STAT1 (dimer)	0.017	0	-10000	0	-10000	0	0
FKBP4	0.008	0.027	-10000	0	-0.52	1	1
FKBP5	0.007	0.036	-10000	0	-0.5	2	2
GR alpha/HSP90/FKBP51/HSP90	0.09	0.1	0.28	44	-10000	0	44
PRL	-0.066	0.13	-10000	0	-0.6	3	3
cortisol/GR alpha (dimer)/TIF2	0.21	0.26	0.54	106	-10000	0	106
RELA	-0.029	0.085	-10000	0	-10000	0	0
FGG	-0.01	0.33	0.48	44	-0.48	86	130
GR beta/TIF2	0.094	0.12	0.31	52	-10000	0	52
IFNG	-0.22	0.26	-10000	0	-0.69	55	55
apoptosis	-0.02	0.16	0.46	10	-0.57	12	22
CREB1	-0.007	0.05	-10000	0	-10000	0	0
histone acetylation	-0.029	0.14	0.28	6	-0.36	27	33
BGLAP	-0.062	0.13	-10000	0	-0.48	9	9
GR/PKAc	0.088	0.099	0.28	40	-10000	0	40
NF kappa B1 p50/RelA	-0.049	0.15	-10000	0	-0.44	15	15
SMARCD1	0.011	0.006	-10000	0	-10000	0	0
MDM2	0.073	0.097	0.25	52	-0.24	1	53
GATA3	0.011	0.045	-10000	0	-0.5	3	3
AKT1	0	0	-10000	0	-10000	0	0
CSF2	-0.12	0.31	-10000	0	-1.1	33	33
GSK3B	0.009	0.005	-10000	0	-10000	0	0
NR1I3	0.004	0.15	0.48	7	-0.55	5	12
CSN2	0.11	0.17	0.4	41	-10000	0	41
BRG1/BAF155/BAF170/BAF60A	0.017	0.027	-10000	0	-0.32	1	1
NFATC1	0.008	0.045	-10000	0	-0.5	3	3
POU2F1	0.01	0.015	-10000	0	-10000	0	0
CDKN1A	0.025	0.067	-10000	0	-1.3	1	1
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.001	0.006	-10000	0	-10000	0	0
SFN	-0.001	0.074	-10000	0	-0.52	8	8
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.084	0.1	0.28	40	-10000	0	40
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.033	0.24	0.46	7	-0.81	29	36
JUN	-0.17	0.18	-10000	0	-0.47	61	61
IL4	-0.077	0.15	-10000	0	-0.56	12	12
CDK5R1	-0.006	0.087	-10000	0	-0.52	11	11
PRKACA	0.01	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.13	0.22	0.21	1	-0.49	69	70
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.091	0.1	0.28	42	-10000	0	42
cortisol/GR alpha (monomer)	0.24	0.32	0.64	110	-10000	0	110
NCOA2	0.007	0.036	-10000	0	-0.5	2	2
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.08	0.15	-10000	0	-0.56	30	30
AP-1/NFAT1-c-4	-0.28	0.28	-10000	0	-0.65	107	107
AFP	-0.13	0.17	-10000	0	-0.63	13	13
SUV420H1	0.01	0	-10000	0	-10000	0	0
IRF1	0.13	0.15	0.41	41	-10000	0	41
TP53	0.026	0.026	-10000	0	-0.48	1	1
PPP5C	0.01	0	-10000	0	-10000	0	0
KRT17	-0.25	0.31	-10000	0	-0.73	84	84
KRT14	-0.18	0.19	-10000	0	-0.52	48	48
TBP	0.017	0	-10000	0	-10000	0	0
CREBBP	0.051	0.062	-10000	0	-0.26	1	1
HDAC1	0.007	0.004	-10000	0	-10000	0	0
HDAC2	0.014	0.023	-10000	0	-10000	0	0
AP-1	-0.28	0.28	-10000	0	-0.66	107	107
MAPK14	0.009	0.005	-10000	0	-10000	0	0
MAPK10	-0.051	0.16	-10000	0	-0.5	46	46
MAPK11	0.005	0.045	-10000	0	-0.5	3	3
KRT5	-0.4	0.5	-10000	0	-1.1	114	114
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	-0.51	46	46
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.12	0.18	0.49	50	-10000	0	50
MAPK3	0.009	0.006	-10000	0	-10000	0	0
MAPK1	0.009	0.005	-10000	0	-10000	0	0
ICAM1	-0.13	0.24	-10000	0	-0.62	44	44
NFKB1	-0.029	0.085	-10000	0	-0.26	7	7
MAPK8	-0.14	0.17	-10000	0	-0.44	61	61
MAPK9	0.009	0.005	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.024	0.17	0.47	10	-0.6	12	22
BAX	0.028	0.022	-10000	0	-10000	0	0
POMC	-0.18	0.31	-10000	0	-0.99	32	32
EP300	0.051	0.063	-10000	0	-0.26	1	1
cortisol/GR alpha (dimer)/p53	0.22	0.26	0.55	105	-10000	0	105
proteasomal ubiquitin-dependent protein catabolic process	0.051	0.074	0.24	13	-0.2	1	14
SGK1	0.095	0.096	-10000	0	-1.1	1	1
IL13	-0.16	0.19	-10000	0	-0.62	23	23
IL6	-0.28	0.44	-10000	0	-0.95	108	108
PRKACG	0.002	0.004	-10000	0	-10000	0	0
IL5	-0.14	0.16	-10000	0	-0.57	15	15
IL2	-0.2	0.23	-10000	0	-0.63	54	54
CDK5	0.009	0.004	-10000	0	-10000	0	0
PRKACB	0.008	0.027	-10000	0	-0.52	1	1
HSP90AA1	0.01	0	-10000	0	-10000	0	0
IL8	-0.13	0.22	-10000	0	-0.61	42	42
CDK5R1/CDK5	-0.009	0.062	-10000	0	-0.37	11	11
NF kappa B1 p50/RelA/PKAc	-0.019	0.11	-10000	0	-0.36	9	9
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.21	0.24	0.52	105	-10000	0	105
SMARCA4	0.01	0.026	-10000	0	-0.5	1	1
chromatin remodeling	0.13	0.14	0.37	64	-10000	0	64
NF kappa B1 p50/RelA/Cbp	0.016	0.14	0.37	3	-0.39	8	11
JUN (dimer)	-0.17	0.18	-10000	0	-0.47	61	61
YWHAH	0.01	0	-10000	0	-10000	0	0
VIPR1	-0.36	0.43	-10000	0	-0.86	166	166
NR3C1	0.14	0.19	0.45	68	-10000	0	68
NR4A1	-0.1	0.22	-10000	0	-0.5	89	89
TIF2/SUV420H1	-0.002	0.025	-10000	0	-0.35	2	2
MAPKKK cascade	-0.02	0.16	0.46	10	-0.57	12	22
cortisol/GR alpha (dimer)/Src-1	0.22	0.26	0.55	107	-10000	0	107
PBX1	-0.005	0.086	-10000	0	-0.5	11	11
POU1F1	0.001	0.035	-10000	0	-0.62	1	1
SELE	-0.22	0.4	-10000	0	-1	67	67
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.13	0.14	0.37	64	-10000	0	64
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.21	0.24	0.52	105	-10000	0	105
mol:cortisol	0.13	0.19	0.38	106	-0.21	9	115
MMP1	-0.28	0.19	-10000	0	-0.47	125	125

×

p75(NTR)-mediated signaling

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
Sortilin/TRAF6	-0.002	0.025	-9999	-0.35	2	2
Necdin/E2F1	-0.011	0.062	-9999	-0.36	12	12
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.03	0.08	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/BEX1	-0.12	0.16	-9999	-0.32	146	146
NT-4/5 (dimer)/p75(NTR)	-0.031	0.1	-9999	-0.37	33	33
IKBKB	0.01	0	-9999	-10000	0	0
AKT1	0.002	0.085	-9999	-10000	0	0
IKBKG	0.01	0	-9999	-10000	0	0
BDNF	-0.23	0.26	-9999	-0.5	186	186
MGDIs/NGR/p75(NTR)/LINGO1	-0.053	0.12	-9999	-0.31	66	66
FURIN	-0.005	0.087	-9999	-0.52	11	11
proBDNF (dimer)/p75(NTR)/Sortilin	-0.15	0.16	-9999	-0.3	194	194
LINGO1	-0.063	0.18	-9999	-0.52	54	54
Sortilin/TRAF6/NRIF	-0.002	0.02	-9999	-10000	0	0
proBDNF (dimer)	-0.23	0.26	-9999	-0.5	186	186
NTRK1	-0.014	0.11	-9999	-0.5	18	18
RTN4R	0.009	0.026	-9999	-0.5	1	1
neuron apoptosis	-0.099	0.15	-9999	-0.41	23	23
IRAK1	0.008	0.027	-9999	-0.52	1	1
SHC1	-0.013	0.1	-9999	-0.3	43	43
ARHGDIA	0.01	0	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
Gamma Secretase	-0.001	0.017	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.03	0.084	-9999	-0.26	45	45
MAGEH1	0.01	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.034	0.093	-9999	-0.29	27	27
Mammalian IAPs/DIABLO	-0.004	0.033	-9999	-0.27	4	4
proNGF (dimer)	-0.03	0.14	-9999	-0.51	30	30
MAGED1	0.008	0.027	-9999	-0.52	1	1
APP	0.01	0	-9999	-10000	0	0
NT-4/5 (dimer)	-0.018	0.12	-9999	-0.5	21	21
ZNF274	0.01	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	-0.027	0.077	-9999	-0.25	26	26
NGF	-0.03	0.14	-9999	-0.51	30	30
cell cycle arrest	0.011	0.11	-9999	-0.29	19	19
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.008	0.063	-9999	-0.23	1	1
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.026	0.086	-9999	-0.3	33	33
NCSTN	0.01	0	-9999	-10000	0	0
mol:GTP	-0.033	0.094	-9999	-0.3	44	44
PSENEN	0.008	0.027	-9999	-0.52	1	1
mol:ceramide	-0.007	0.092	-9999	-0.26	45	45
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.015	0.058	-9999	-0.39	1	1
p75(NTR)/beta APP	-0.012	0.065	-9999	-0.36	13	13
BEX1	-0.14	0.23	-9999	-0.5	116	116
mol:GDP	-0.021	0.1	-9999	-0.31	43	43
NGF (dimer)	-0.082	0.13	-9999	-0.29	112	112
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.047	0.1	-9999	-0.28	66	66
PIK3R1	0.01	0	-9999	-10000	0	0
RAC1/GTP	-0.028	0.08	-9999	-0.26	43	43
MYD88	0.01	0	-9999	-10000	0	0
CHUK	0.01	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.034	0.095	-9999	-0.3	44	44
RHOB	0.01	0	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
MAGE-G1/E2F1	-0.006	0.045	-9999	-0.37	6	6
NT3 (dimer)	-0.023	0.12	-9999	-0.5	25	25
TP53	-0.094	0.14	-9999	-0.46	7	7
PRDM4	-0.007	0.093	-9999	-0.26	45	45
BDNF (dimer)	-0.29	0.22	-9999	-0.39	290	290
PIK3CA	0.01	0	-9999	-10000	0	0
SORT1	0.007	0.036	-9999	-0.5	2	2
activation of caspase activity	-0.03	0.079	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.03	0.084	-9999	-0.26	45	45
RHOC	0.01	0	-9999	-10000	0	0
XIAP	0.01	0	-9999	-10000	0	0
MAPK10	-0.09	0.15	-9999	-0.4	41	41
DIABLO	0.01	0	-9999	-10000	0	0
SMPD2	-0.007	0.093	-9999	-0.26	45	45
APH1B	0.009	0.026	-9999	-0.5	1	1
APH1A	0.01	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.034	0.095	-9999	-0.3	45	45
PSEN1	0.01	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-9999	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.034	0.12	-9999	-0.39	34	34
MAPK8	-0.066	0.12	-9999	-0.37	21	21
MAPK9	-0.066	0.12	-9999	-0.37	21	21
APAF1	0.01	0	-9999	-10000	0	0
NTF3	-0.023	0.12	-9999	-0.5	25	25
NTF4	-0.018	0.12	-9999	-0.5	21	21
NDN	0.002	0.063	-9999	-0.5	6	6
RAC1/GDP	0	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.025	0.069	-9999	-10000	0	0
p75 CTF/Sortilin/TRAF6/NRIF	-0.001	0.018	-9999	-0.26	2	2
RhoA-B-C/GTP	-0.033	0.094	-9999	-0.3	44	44
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.12	0.13	-9999	-0.49	7	7
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.13	0.14	-9999	-0.27	194	194
PRKACB	0.008	0.027	-9999	-0.52	1	1
proBDNF (dimer)/p75 ECD	-0.17	0.18	-9999	-0.35	186	186
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	0.002	0.064	-9999	-0.51	6	6
BIRC2	0.01	0	-9999	-10000	0	0
neuron projection morphogenesis	0.019	0.11	-9999	-0.27	13	13
BAD	-0.069	0.13	-9999	-0.42	17	17
RIPK2	0.01	0	-9999	-10000	0	0
NGFR	-0.007	0.093	-9999	-0.51	13	13
CYCS	0	0.09	-9999	-0.5	1	1
ADAM17	0.01	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.029	0.083	-9999	-0.27	26	26
BCL2L11	-0.069	0.13	-9999	-0.42	17	17
BDNF (dimer)/p75(NTR)	-0.18	0.18	-9999	-0.36	194	194
PI3K	-0.029	0.083	-9999	-0.27	26	26
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.03	0.084	-9999	-0.26	45	45
NDNL2	0.01	0	-9999	-10000	0	0
YWHAE	0.01	0	-9999	-10000	0	0
PRKCI	0.01	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)	-0.04	0.11	-9999	-0.36	43	43
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.031	0.087	-9999	-0.27	45	45
TRAF6	0.01	0	-9999	-10000	0	0
RAC1	0.01	0	-9999	-10000	0	0
PRKCZ	0.006	0.045	-9999	-0.5	3	3
PLG	-0.01	0.078	-9999	-0.52	9	9
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.12	0.16	-9999	-0.47	26	26
SQSTM1	0.008	0.027	-9999	-0.52	1	1
NGFRAP1	0.005	0.051	-9999	-0.5	4	4
CASP3	-0.063	0.12	-9999	-0.39	17	17
E2F1	0.002	0.065	-9999	-0.52	6	6
CASP9	0.01	0	-9999	-10000	0	0
IKK complex	-0.028	0.071	-9999	-0.39	3	3
NGF (dimer)/TRKA	-0.044	0.12	-9999	-0.37	47	47
MMP7	-0.081	0.2	-9999	-0.52	68	68
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.028	0.077	-9999	-10000	0	0
MMP3	-0.21	0.26	-9999	-0.52	161	161
APAF-1/Caspase 9	-0.022	0.06	-9999	-0.37	2	2

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.002	0.021	-9999	-0.3	2	2
ARNO/beta Arrestin1-2	-0.093	0.11	-9999	-0.36	17	17
EGFR	-0.007	0.093	-9999	-0.51	13	13
EPHA2	0.001	0.068	-9999	-0.5	7	7
USP6	0.01	0	-9999	-10000	0	0
IQSEC1	0.008	0.026	-9999	-0.5	1	1
EGFR/EGFR/EGF/EGF	-0.085	0.16	-9999	-0.38	88	88
ARRB2	-0.005	0.053	-9999	-0.19	30	30
mol:GTP	0.011	0.023	-9999	-0.13	2	2
ARRB1	0.005	0.051	-9999	-0.5	4	4
FBXO8	0.01	0	-9999	-10000	0	0
TSHR	-0.046	0.16	-9999	-0.52	41	41
EGF	-0.095	0.21	-9999	-0.52	78	78
somatostatin receptor activity	0	0	-9999	-0.001	79	79
ARAP2	-0.011	0.1	-9999	-0.5	16	16
mol:GDP	-0.083	0.12	-9999	-0.26	86	86
mol:PI-3-4-5-P3	0	0	-9999	-0.001	57	57
ITGA2B	-0.047	0.16	-9999	-0.5	43	43
ARF6	0.01	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.005	0.037	-9999	-0.26	8	8
ADAP1	0.008	0.026	-9999	-0.5	1	1
KIF13B	0.009	0.026	-9999	-0.5	1	1
HGF/MET	-0.042	0.12	-9999	-0.38	43	43
PXN	0.01	0	-9999	-10000	0	0
ARF6/GTP	-0.08	0.11	-9999	-0.25	78	78
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.071	0.14	-9999	-0.32	88	88
ADRB2	-0.19	0.25	-9999	-0.5	151	151
receptor agonist activity	0	0	-9999	0	89	89
actin filament binding	0	0	-9999	0	92	92
SRC	0.01	0	-9999	-10000	0	0
ITGB3	-0.024	0.13	-9999	-0.52	25	25
GNAQ	0.008	0.026	-9999	-0.5	1	1
EFA6/PI-4-5-P2	0	0	-9999	-0.001	63	63
ARF6/GDP	-0.01	0.078	-9999	-0.33	11	11
ARF6/GDP/GULP/ACAP1	-0.076	0.095	-9999	-0.31	25	25
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.045	0.1	-9999	-0.52	1	1
ACAP1	0.007	0.036	-9999	-0.5	2	2
ACAP2	0.008	0.027	-9999	-0.52	1	1
LHCGR/beta Arrestin2	-0.021	0.073	-9999	-0.28	30	30
EFNA1	0.009	0.026	-9999	-0.5	1	1
HGF	-0.016	0.11	-9999	-0.5	20	20
CYTH3	0.007	0.027	-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	61	61
endosomal lumen acidification	0	0	-9999	0	28	28
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	0.009	0.026	-9999	-0.5	1	1
GNAQ/ARNO	0.007	0.015	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	26	26
MET	-0.025	0.13	-9999	-0.51	26	26
GNA14	-0.006	0.088	-9999	-0.5	12	12
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	64	64
GNA11	0.008	0.026	-9999	-0.5	1	1
LHCGR	-0.035	0.14	-9999	-0.52	30	30
AGTR1	-0.14	0.23	-9999	-0.5	116	116
desensitization of G-protein coupled receptor protein signaling pathway	-0.021	0.073	-9999	-0.28	30	30
IPCEF1/ARNO	-0.05	0.1	-9999	-0.47	3	3
alphaIIb/beta3 Integrin	-0.062	0.14	-9999	-0.36	67	67

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.004	0.019	-10000	0	-10000	0	0
AES	0.003	0.016	-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	-0.081	0.2	-10000	0	-0.5	70	70
TLE1	0.004	0.016	-10000	0	-10000	0	0
MACF1	0.005	0.051	-10000	0	-0.5	4	4
CTNNB1	0.092	0.079	0.25	11	-10000	0	11
WIF1	-0.34	0.24	-10000	0	-0.5	269	269
beta catenin/RanBP3	0.012	0.088	0.39	18	-10000	0	18
KREMEN2	-0.12	0.23	-10000	0	-0.52	95	95
DKK1	-0.12	0.23	-10000	0	-0.51	99	99
beta catenin/beta TrCP1	0.092	0.075	0.24	11	-10000	0	11
FZD1	0.01	0.001	-10000	0	-10000	0	0
AXIN2	-0.027	0.24	-10000	0	-1.3	14	14
AXIN1	0.011	0.001	-10000	0	-10000	0	0
RAN	0.007	0.038	-10000	0	-0.52	2	2
Axin1/APC/GSK3/beta catenin	0.006	0.021	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.075	0.061	0.27	1	-10000	0	1
Axin1/APC/GSK3	0.022	0.062	0.2	35	-10000	0	35
Axin1/APC/GSK3/beta catenin/Macf1	0.067	0.044	-10000	0	-10000	0	0
HNF1A	-0.092	0.2	-10000	0	-0.52	72	72
CTBP1	0.004	0.017	-10000	0	-10000	0	0
MYC	0.005	0.11	-10000	0	-1.4	2	2
RANBP3	0.01	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.12	0.19	-10000	0	-0.36	135	135
NKD1	-0.055	0.17	-10000	0	-0.5	49	49
TCF4	0.001	0.04	-10000	0	-0.5	2	2
TCF3	0.004	0.017	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	-0.005	0.035	-10000	0	-0.27	3	3
Ran/GTP	-0.001	0.027	-10000	0	-0.38	2	2
CtBP/CBP/TCF/TLE1/AES	0.003	0.11	0.44	19	-10000	0	19
LEF1	0.001	0.041	-10000	0	-0.52	2	2
DVL1	0.073	0.054	0.19	1	-0.27	1	2
CSNK2A1	0.01	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.077	0.068	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.15	0.19	-10000	0	-0.36	162	162
LRP6	0.01	0.001	-10000	0	-10000	0	0
CSNK1A1	0.004	0.019	-10000	0	-10000	0	0
NLK	0.01	0.002	-10000	0	-10000	0	0
CCND1	-0.004	0.16	-10000	0	-1.4	5	5
WNT1	0	0.07	-10000	0	-0.52	7	7
GSK3A	0.011	0.001	-10000	0	-10000	0	0
GSK3B	0.01	0.002	-10000	0	-10000	0	0
FRAT1	0.009	0.002	-10000	0	-10000	0	0
PPP2R5D	0.074	0.088	0.3	49	-10000	0	49
APC	0.025	0.038	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.15	0.1	0.22	264	-10000	0	264
CREBBP	0.004	0.017	-10000	0	-10000	0	0

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.006	0.045	-10000	0	-0.5	3	3
EPHB2	-0.053	0.17	-10000	0	-0.52	47	47
EFNB1	0.011	0.05	-10000	0	-0.36	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.061	0.12	-10000	0	-0.48	13	13
Ephrin B2/EPHB1-2	-0.064	0.13	-10000	0	-0.3	88	88
neuron projection morphogenesis	-0.059	0.11	-10000	0	-0.46	13	13
Ephrin B1/EPHB1-2/Tiam1	-0.063	0.13	-10000	0	-0.52	13	13
DNM1	0.003	0.059	-10000	0	-0.52	5	5
cell-cell signaling	0.001	0.002	-10000	0	-10000	0	0
MAP2K4	-0.051	0.19	-10000	0	-0.57	45	45
YES1	-0.091	0.26	-10000	0	-0.8	45	45
Ephrin B1/EPHB1-2/NCK2	-0.059	0.12	-10000	0	-0.5	11	11
PI3K	-0.052	0.19	-10000	0	-0.58	45	45
mol:GDP	-0.066	0.13	-10000	0	-0.52	13	13
ITGA2B	-0.047	0.16	-10000	0	-0.5	43	43
endothelial cell proliferation	-0.002	0.026	-10000	0	-0.3	3	3
FYN	-0.091	0.26	-10000	0	-0.8	45	45
MAP3K7	-0.07	0.2	-10000	0	-0.61	45	45
FGR	-0.1	0.26	-10000	0	-0.82	45	45
TIAM1	0.001	0.068	-10000	0	-0.5	7	7
PIK3R1	0.01	0	-10000	0	-10000	0	0
RGS3	0.01	0	-10000	0	-10000	0	0
cell adhesion	-0.079	0.2	-10000	0	-0.57	45	45
LYN	-0.091	0.26	-10000	0	-0.8	45	45
Ephrin B1/EPHB1-2/Src Family Kinases	-0.085	0.24	-10000	0	-0.74	45	45
Ephrin B1/EPHB1-2	-0.079	0.21	-10000	0	-0.67	45	45
SRC	-0.09	0.25	-10000	0	-0.8	45	45
ITGB3	-0.024	0.13	-10000	0	-0.52	25	25
EPHB1	-0.052	0.17	-10000	0	-0.52	46	46
EPHB4	0.01	0	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	-0.002	0.026	-10000	0	-0.3	3	3
alphaIIb/beta3 Integrin	-0.062	0.14	-10000	0	-0.36	67	67
BLK	-0.095	0.26	-10000	0	-0.8	45	45
HCK	-0.096	0.26	-10000	0	-0.82	45	45
regulation of stress fiber formation	0.061	0.12	0.5	11	-10000	0	11
MAPK8	-0.042	0.18	-10000	0	-0.54	45	45
Ephrin B1/EPHB1-2/RGS3	-0.059	0.12	-10000	0	-0.5	11	11
endothelial cell migration	-0.058	0.17	-10000	0	-0.52	46	46
NCK2	0.01	0	-10000	0	-10000	0	0
PTPN13	-0.065	0.2	-10000	0	-0.62	45	45
regulation of focal adhesion formation	0.061	0.12	0.5	11	-10000	0	11
chemotaxis	0.061	0.12	0.5	11	-10000	0	11
PIK3CA	0.01	0	-10000	0	-10000	0	0
Rac1/GTP	-0.06	0.12	-10000	0	-0.48	13	13
angiogenesis	-0.078	0.21	-10000	0	-0.66	45	45
LCK	-0.091	0.25	-10000	0	-0.8	45	45

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.007	0.05	-9999	-0.35	8	8
alphaV beta3 Integrin	-0.056	0.12	-9999	-0.31	70	70
PTK2	-0.056	0.15	-9999	-0.44	28	28
IGF1R	0.009	0.026	-9999	-0.5	1	1
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	0.19	-9999	-0.5	66	66
VEGFA	0.01	0	-9999	-10000	0	0
ILK	-0.1	0.19	-9999	-0.5	66	66
ROCK1	0.01	0	-9999	-10000	0	0
AKT1	-0.092	0.18	-9999	-0.47	65	65
PTK2B	0.007	0.082	-9999	-0.49	2	2
alphaV/beta3 Integrin/JAM-A	-0.09	0.15	-9999	-0.52	23	23
CBL	0.01	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.037	0.1	-9999	-0.3	48	48
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.005	0.041	-9999	-0.3	7	7
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.016	0.096	-9999	-0.36	8	8
alphaV/beta3 Integrin/Syndecan-1	-0.019	0.074	-9999	-0.3	25	25
PI4KA	0.01	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.047	0.11	-9999	-0.52	9	9
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.25	0.15	-9999	-0.32	298	298
RPS6KB1	-0.006	0.12	-9999	-0.48	9	9
TLN1	0.009	0.026	-9999	-0.5	1	1
MAPK3	-0.089	0.18	-9999	-0.52	51	51
GPR124	0.006	0.045	-9999	-0.5	3	3
MAPK1	-0.089	0.18	-9999	-0.52	51	51
PXN	0.01	0	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.11	0.15	-9999	-0.3	142	142
cell adhesion	-0.028	0.074	-9999	-0.28	4	4
ANGPTL3	-0.025	0.12	-9999	-0.52	23	23
VEGFR2 homodimer/VEGFA homodimer/Src	-0.006	0.041	-9999	-0.29	8	8
IGF-1R heterotetramer	0.009	0.026	-9999	-0.5	1	1
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	0.001	0.068	-9999	-0.5	7	7
ITGB3	-0.024	0.13	-9999	-0.52	25	25
IGF1	0.002	0.063	-9999	-0.5	6	6
RAC1	0.01	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.021	0.082	-9999	-0.32	26	26
apoptosis	0.01	0	-9999	-10000	0	0
CD47	0.009	0.026	-9999	-0.5	1	1
alphaV/beta3 Integrin/CD47	-0.02	0.075	-9999	-0.3	26	26
VCL	0.01	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.04	0.11	-9999	-0.32	49	49
CSF1	0.006	0.045	-9999	-0.5	3	3
PIK3C2A	-0.1	0.19	-9999	-0.5	66	66
PI4 Kinase/Pyk2	-0.077	0.13	-9999	-0.45	26	26
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.022	0.076	-9999	-0.28	32	32
FAK1/Vinculin	-0.04	0.12	-9999	-0.35	28	28
alphaV beta3/Integrin/ppsTEM5	-0.021	0.083	-9999	-0.32	26	26
RHOA	0.01	0	-9999	-10000	0	0
VTN	-0.083	0.2	-9999	-0.5	71	71
BCAR1	0.009	0.026	-9999	-0.5	1	1
FGF2	-0.054	0.17	-9999	-0.5	49	49
F11R	-0.029	0.12	-9999	-0.35	50	50
alphaV/beta3 Integrin/Lactadherin	-0.019	0.074	-9999	-0.3	25	25
alphaV/beta3 Integrin/TGFBR2	-0.024	0.082	-9999	-0.3	32	32
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.003	0.026	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.018	0.071	-9999	-0.28	25	25
mol:GDP	0	0	-9999	-10000	0	0
FN1	0.005	0.051	-9999	-0.5	4	4
alphaV/beta3 Integrin/Pyk2	-0.022	0.074	-9999	-0.49	2	2
SDC1	0.01	0	-9999	-10000	0	0
VAV3	0.025	0.044	-9999	-0.49	1	1
PTPN11	0.01	0	-9999	-10000	0	0
IRS1	0.009	0.026	-9999	-0.5	1	1
FAK1/Paxillin	-0.04	0.12	-9999	-0.36	22	22
cell migration	-0.03	0.12	-9999	-0.37	12	12
ITGAV	0.01	0	-9999	-10000	0	0
PI3K	-0.079	0.13	-9999	-0.47	23	23
SPP1	-0.38	0.23	-9999	-0.52	293	293
KDR	-0.001	0.072	-9999	-0.5	8	8
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.01	0	-9999	-10000	0	0
COL4A3	-0.15	0.24	-9999	-0.5	122	122
angiogenesis	-0.066	0.21	-9999	-0.52	53	53
Rac1/GTP	-0.005	0.036	-9999	-0.45	1	1
EDIL3	-0.027	0.13	-9999	-0.5	28	28
cell proliferation	-0.024	0.082	-9999	-0.3	32	32

×

Effects of Botulinum toxin

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	-0.081	0.16	-9999	-0.38	92	92
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.042	0.12	-9999	-0.36	46	46
STXBP1	0.006	0.045	-9999	-0.5	3	3
ACh/CHRNA1	-0.034	0.1	-9999	-0.35	34	34
RAB3GAP2/RIMS1/UNC13B	-0.035	0.095	-9999	-0.3	46	46
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	-0.051	0.17	-9999	-0.51	46	46
mol:ACh	-0.015	0.04	-9999	-0.08	95	95
RAB3GAP2	0.01	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.078	0.11	-9999	-0.37	20	20
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.033	0.1	-9999	-0.35	34	34
UNC13B	0.01	0	-9999	-10000	0	0
CHRNA1	-0.036	0.15	-9999	-0.52	34	34
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.033	0.11	-9999	-0.36	34	34
SNAP25	-0.003	0.042	-9999	-0.18	19	19
VAMP2	0.005	0	-9999	-10000	0	0
SYT1	-0.036	0.15	-9999	-0.52	34	34
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.065	0.14	-9999	-0.31	95	95
STX1A/SNAP25 fragment 1/VAMP2	-0.078	0.11	-9999	-0.37	20	20

×

EGFR-dependent Endothelin signaling events

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
HRAS	0.01	0	-9999	-10000	0	0
EGFR	-0.007	0.093	-9999	-0.51	13	13
EGF/EGFR	-0.09	0.14	-9999	-0.27	131	131
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.057	0.11	-9999	-0.5	3	3
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.007	0.036	-9999	-0.5	2	2
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.095	0.21	-9999	-0.52	78	78
EGF/EGFR dimer/SHC	-0.07	0.13	-9999	-0.31	88	88
mol:GDP	-0.057	0.11	-9999	-0.5	3	3
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.06	0.18	-9999	-0.5	54	54
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.051	0.098	-9999	-0.46	3	3
SHC1	0.01	0	-9999	-10000	0	0
HRAS/GDP	-0.053	0.1	-9999	-0.47	3	3
FRAP1	-0.031	0.12	-9999	-0.48	3	3
EGF/EGFR dimer	-0.085	0.16	-9999	-0.38	88	88
SOS1	0.01	0	-9999	-10000	0	0
GRB2	0.01	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.05	0.12	-9999	-0.35	56	56

×

Syndecan-1-mediated signaling events

Figure S31. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S31. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.01	0	-9999	-10000	0	0
CCL5	0.005	0.051	-9999	-0.5	4	4
SDCBP	0.01	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.11	0.11	-9999	-0.35	19	19
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	0.1	-9999	-0.34	22	22
Syndecan-1/Syntenin	-0.1	0.1	-9999	-0.33	19	19
MAPK3	-0.081	0.095	-9999	-0.5	2	2
HGF/MET	-0.042	0.12	-9999	-0.38	43	43
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	0.1	-9999	-0.33	22	22
Syndecan-1/RANTES	-0.1	0.1	-9999	-0.33	22	22
Syndecan-1/CD147	-0.1	0.085	-9999	-0.31	20	20
Syndecan-1/Syntenin/PIP2	-0.11	0.086	-9999	-0.32	19	19
LAMA5	0.006	0.045	-9999	-0.5	3	3
positive regulation of cell-cell adhesion	-0.1	0.084	-9999	-0.31	19	19
MMP7	-0.081	0.2	-9999	-0.52	68	68
HGF	-0.016	0.11	-9999	-0.5	20	20
Syndecan-1/CASK	-0.11	0.1	-9999	-0.33	19	19
Syndecan-1/HGF/MET	-0.13	0.12	-9999	-0.38	49	49
regulation of cell adhesion	-0.073	0.093	-9999	-0.48	2	2
HPSE	0.007	0.038	-9999	-0.52	2	2
positive regulation of cell migration	-0.11	0.11	-9999	-0.35	19	19
SDC1	-0.11	0.11	-9999	-0.35	19	19
Syndecan-1/Collagen	-0.11	0.11	-9999	-0.35	19	19
PPIB	0.008	0.027	-9999	-0.52	1	1
MET	-0.025	0.13	-9999	-0.51	26	26
PRKACA	0.01	0	-9999	-10000	0	0
MMP9	-0.082	0.2	-9999	-0.52	68	68
MAPK1	-0.081	0.095	-9999	-0.5	2	2
homophilic cell adhesion	-0.11	0.11	-9999	-0.35	19	19
MMP1	-0.35	0.24	-9999	-0.52	270	270

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.04	0.11	-10000	0	-0.31	51	51
fibroblast growth factor receptor signaling pathway	-0.04	0.11	-10000	0	-0.31	51	51
LAMA1	-0.021	0.12	-10000	0	-0.51	23	23
PRNP	0.007	0.036	-10000	0	-0.5	2	2
GPC1/SLIT2	-0.08	0.15	-10000	0	-0.35	89	89
SMAD2	0.019	0.045	-10000	0	-10000	0	0
GPC1/PrPc/Cu2+	-0.003	0.03	-10000	0	-0.3	4	4
GPC1/Laminin alpha1	-0.023	0.091	-10000	0	-0.38	24	24
TDGF1	-0.02	0.12	-10000	0	-0.51	22	22
CRIPTO/GPC1	-0.022	0.087	-10000	0	-0.36	24	24
APP/GPC1	-0.002	0.025	-10000	0	-0.35	2	2
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0.002	0.077	-10000	0	-0.3	24	24
FLT1	0.01	0	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	-0.007	0.046	-10000	0	-0.29	10	10
SERPINC1	-0.002	0.07	-10000	0	-0.52	7	7
FYN	0.001	0.081	-10000	0	-0.31	24	24
FGR	-0.024	0.12	-10000	0	-0.32	52	52
positive regulation of MAPKKK cascade	-0.014	0.12	-10000	0	-0.38	25	25
SLIT2	-0.1	0.21	-10000	0	-0.5	87	87
GPC1/NRG	-0.07	0.14	-10000	0	-0.35	78	78
NRG1	-0.089	0.2	-10000	0	-0.5	76	76
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.001	0.021	-10000	0	-0.29	2	2
LYN	0.002	0.077	-10000	0	-0.3	24	24
mol:Spermine	0.007	0.026	-10000	0	-0.36	2	2
cell growth	-0.04	0.11	-10000	0	-0.31	51	51
BMP signaling pathway	-0.007	0.036	0.5	2	-10000	0	2
SRC	0.002	0.077	-10000	0	-0.3	24	24
TGFBR1	0.008	0.027	-10000	0	-0.52	1	1
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.067	0.18	-10000	0	-0.5	59	59
GPC1	0.007	0.036	-10000	0	-0.5	2	2
TGFBR1 (dimer)	0.008	0.027	-10000	0	-0.52	1	1
VEGFA	0.01	0	-10000	0	-10000	0	0
BLK	-0.041	0.13	-10000	0	-0.31	74	74
HCK	-0.011	0.1	-10000	0	-0.31	38	38
FGF2	-0.054	0.17	-10000	0	-0.5	49	49
FGFR1	0.006	0.045	-10000	0	-0.51	3	3
VEGFR1 homodimer	0.01	0	-10000	0	-10000	0	0
TGFBR2	0.001	0.068	-10000	0	-0.5	7	7
cell death	-0.002	0.025	-10000	0	-0.35	2	2
ATIII/GPC1	-0.008	0.055	-10000	0	-0.36	9	9
PLA2G2A/GPC1	-0.055	0.13	-10000	0	-0.36	61	61
LCK	0	0.08	-10000	0	-0.3	26	26
neuron differentiation	-0.07	0.14	-10000	0	-0.35	78	78
PrPc/Cu2+	-0.002	0.026	-10000	0	-0.36	2	2
APP	0.01	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.001	0.068	-10000	0	-0.5	7	7

×

Thromboxane A2 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
TGM2	0.003	0.052	-10000	0	-0.5	4	4
GNB1/GNG2	-0.032	0.067	-10000	0	-0.18	61	61
AKT1	0.007	0.095	-10000	0	-0.2	62	62
EGF	-0.095	0.21	-10000	0	-0.52	78	78
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.012	0.086	-10000	0	-0.42	7	7
mol:Ca2+	-0.009	0.14	-10000	0	-0.3	63	63
LYN	0.03	0.047	-10000	0	-0.37	3	3
RhoA/GTP	-0.022	0.045	-10000	0	-0.14	16	16
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.01	0.15	-10000	0	-0.34	63	63
GNG2	0.009	0.026	-10000	0	-0.5	1	1
ARRB2	0.01	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.024	0.041	-10000	0	-0.34	2	2
G beta5/gamma2	-0.041	0.088	-10000	0	-0.24	61	61
PRKCH	-0.013	0.15	-10000	0	-0.34	63	63
DNM1	0.003	0.059	-10000	0	-0.52	5	5
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	-0.001	0.072	-10000	0	-0.5	8	8
G12 family/GTP	-0.053	0.11	-10000	0	-0.3	63	63
ADRBK1	0.01	0	-10000	0	-10000	0	0
ADRBK2	0.009	0.026	-10000	0	-0.5	1	1
RhoA/GTP/ROCK1	0	0	-10000	0	-10000	0	0
mol:GDP	-0.003	0.092	0.34	9	-10000	0	9
mol:NADP	-0.004	0.082	-10000	0	-0.51	10	10
RAB11A	0.01	0	-10000	0	-10000	0	0
PRKG1	-0.04	0.15	-10000	0	-0.5	38	38
mol:IP3	-0.018	0.17	-10000	0	-0.38	63	63
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	-0.036	0.22	-10000	0	-0.52	63	63
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.001	0.09	-10000	0	-0.37	4	4
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.021	0.071	-10000	0	-0.4	6	6
RHOA	0.01	0	-10000	0	-10000	0	0
PTGIR	0.001	0.068	-10000	0	-0.5	7	7
PRKCB1	-0.019	0.16	-10000	0	-0.37	63	63
GNAQ	0.009	0.026	-10000	0	-0.5	1	1
mol:L-citrulline	-0.004	0.082	-10000	0	-0.51	10	10
TXA2/TXA2-R family	-0.036	0.22	-10000	0	-0.52	63	63
LCK	0.029	0.051	-10000	0	-0.37	4	4
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.008	0.048	-10000	0	-0.5	2	2
TXA2-R family/G12 family/GDP/G beta/gamma	0.023	0.02	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.008	0.046	-10000	0	-0.49	2	2
MAPK14	0.004	0.1	-10000	0	-0.22	61	61
TGM2/GTP	-0.023	0.18	-10000	0	-0.42	63	63
MAPK11	0.003	0.11	-10000	0	-0.23	61	61
ARHGEF1	0.002	0.081	-10000	0	-0.17	61	61
GNAI2	0.01	0	-10000	0	-10000	0	0
JNK cascade	-0.018	0.17	-10000	0	-0.38	63	63
RAB11/GDP	0.01	0.001	-10000	0	-10000	0	0
ICAM1	-0.007	0.13	-10000	0	-0.29	62	62
cAMP biosynthetic process	-0.018	0.15	-10000	0	-0.35	63	63
Gq family/GTP/EBP50	0.015	0.05	-10000	0	-0.38	3	3
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0.03	0.047	-10000	0	-0.37	3	3
GNB5	0.01	0	-10000	0	-10000	0	0
GNB1	0.01	0	-10000	0	-10000	0	0
EGF/EGFR	0.009	0.079	-10000	0	-0.32	10	10
VCAM1	-0.009	0.13	-10000	0	-0.29	61	61
TP beta/Gq family/GDP/G beta5/gamma2	0.024	0.041	-10000	0	-0.34	2	2
platelet activation	0.004	0.14	-10000	0	-0.3	63	63
PGI2/IP	-0.006	0.048	-10000	0	-0.36	7	7
PRKACA	0.005	0.061	-10000	0	-0.3	13	13
Gq family/GDP/G beta5/gamma2	0.023	0.043	-10000	0	-0.29	4	4
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	0.013	0.058	-10000	0	-0.57	2	2
mol:DAG	-0.023	0.18	-10000	0	-0.42	63	63
EGFR	-0.007	0.093	-10000	0	-0.51	13	13
TXA2/TP alpha	-0.031	0.21	-10000	0	-0.48	63	63
Gq family/GTP	-0.008	0.052	-10000	0	-0.25	13	13
YES1	0.03	0.047	-10000	0	-0.37	3	3
GNAI2/GTP	-0.008	0.046	-10000	0	-0.43	3	3
PGD2/DP	-0.007	0.051	-10000	0	-0.36	8	8
SLC9A3R1	0.007	0.038	-10000	0	-0.52	2	2
FYN	0.029	0.048	-10000	0	-0.37	3	3
mol:NO	-0.004	0.082	-10000	0	-0.51	10	10
GNA15	0.01	0	-10000	0	-10000	0	0
PGK/cGMP	-0.037	0.1	-10000	0	-0.31	47	47
RhoA/GDP	0.01	0.001	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.01	0.055	-10000	0	-0.45	4	4
NOS3	-0.004	0.082	-10000	0	-0.51	10	10
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCA	-0.014	0.15	-10000	0	-0.35	64	64
PRKCB	-0.014	0.16	-10000	0	-0.36	64	64
PRKCE	-0.012	0.16	-10000	0	-0.35	64	64
PRKCD	-0.016	0.16	-10000	0	-0.37	63	63
PRKCG	-0.025	0.17	-10000	0	-0.39	63	63
muscle contraction	-0.031	0.21	-10000	0	-0.48	63	63
PRKCZ	-0.01	0.15	-10000	0	-0.34	63	63
ARR3	0.001	0.027	-10000	0	-0.52	1	1
TXA2/TP beta	-0.009	0.052	-10000	0	-0.48	3	3
PRKCQ	-0.034	0.17	-10000	0	-0.38	64	64
MAPKKK cascade	-0.03	0.2	-10000	0	-0.45	63	63
SELE	-0.024	0.16	-10000	0	-0.39	61	61
TP beta/GNAI2/GDP/G beta/gamma	-0.008	0.049	-10000	0	-0.46	3	3
ROCK1	0.01	0	-10000	0	-10000	0	0
GNA14	-0.006	0.088	-10000	0	-0.5	12	12
chemotaxis	-0.046	0.25	-10000	0	-0.59	63	63
GNA12	0.01	0	-10000	0	-10000	0	0
GNA13	0.01	0	-10000	0	-10000	0	0
GNA11	0.009	0.026	-10000	0	-0.5	1	1
Rac1/GTP	0	0	-10000	0	-10000	0	0

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	-0.067	0.19	-10000	0	-0.52	59	59
NFATC2	0.007	0.16	-10000	0	-0.66	13	13
NFATC3	-0.012	0.081	-10000	0	-0.3	7	7
CD40LG	-0.079	0.36	-10000	0	-0.94	42	42
ITCH	-0.011	0.1	-10000	0	-10000	0	0
CBLB	-0.011	0.1	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.12	0.23	-10000	0	-0.94	16	16
JUNB	0.007	0.036	-10000	0	-0.5	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.053	0.11	-10000	0	-0.27	77	77
T cell anergy	-0.061	0.16	-10000	0	-0.38	77	77
TLE4	0.024	0.14	-10000	0	-0.79	7	7
Jun/NFAT1-c-4/p21SNFT	-0.12	0.3	-10000	0	-0.92	40	40
AP-1/NFAT1-c-4	-0.094	0.39	-10000	0	-1.1	39	39
IKZF1	0.025	0.14	-10000	0	-0.81	7	7
T-helper 2 cell differentiation	0.009	0.18	-10000	0	-0.84	9	9
AP-1/NFAT1	-0.051	0.12	-10000	0	-0.48	18	18
CALM1	-0.012	0.067	-10000	0	-10000	0	0
EGR2	-0.049	0.39	-10000	0	-1.3	25	25
EGR3	-0.092	0.47	-10000	0	-1.4	44	44
NFAT1/FOXP3	-0.043	0.17	-10000	0	-0.49	20	20
EGR1	-0.028	0.13	-10000	0	-0.5	29	29
JUN	0.005	0.04	-10000	0	-0.5	2	2
EGR4	-0.043	0.16	-10000	0	-0.52	38	38
mol:Ca2+	-0.023	0.071	-10000	0	-10000	0	0
GBP3	0.011	0.17	-10000	0	-0.72	17	17
FOSL1	-0.022	0.13	-10000	0	-0.52	24	24
NFAT1-c-4/MAF/IRF4	-0.11	0.29	-10000	0	-0.86	44	44
DGKA	0.028	0.12	-10000	0	-0.66	5	5
CREM	0.009	0	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.14	0.33	-10000	0	-0.91	50	50
CTLA4	-0.026	0.16	-10000	0	-0.6	10	10
NFAT1-c-4 (dimer)/EGR1	-0.13	0.34	-10000	0	-0.94	48	48
NFAT1-c-4 (dimer)/EGR4	-0.13	0.31	-10000	0	-0.88	48	48
FOS	-0.032	0.14	-10000	0	-0.51	30	30
IFNG	-0.083	0.22	-10000	0	-0.9	17	17
T cell activation	0.01	0.19	-10000	0	-0.7	12	12
MAF	0.009	0.026	-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	0.032	0.27	0.73	40	-10000	0	40
TNF	-0.083	0.35	-10000	0	-0.93	45	45
FASLG	-0.11	0.48	-10000	0	-1.3	51	51
TBX21	-0.016	0.11	-10000	0	-0.5	19	19
BATF3	0.009	0.027	-10000	0	-0.52	1	1
PRKCQ	-0.062	0.18	-10000	0	-0.5	57	57
PTPN1	0.029	0.12	-10000	0	-0.66	5	5
NFAT1-c-4/ICER1	-0.11	0.3	-10000	0	-0.87	47	47
GATA3	0.007	0.045	-10000	0	-0.51	3	3
T-helper 1 cell differentiation	-0.056	0.22	-10000	0	-0.87	17	17
IL2RA	-0.12	0.22	-10000	0	-0.76	23	23
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	0.029	0.12	-10000	0	-0.73	4	4
E2F1	0.006	0.065	-10000	0	-0.51	6	6
PPARG	-0.059	0.18	-10000	0	-0.5	53	53
SLC3A2	0.029	0.12	-10000	0	-0.66	5	5
IRF4	-0.007	0.094	-10000	0	-0.52	13	13
PTGS2	-0.094	0.37	-10000	0	-0.98	43	43
CSF2	-0.087	0.36	-10000	0	-0.96	43	43
JunB/Fra1/NFAT1-c-4	-0.12	0.3	-10000	0	-0.88	43	43
IL4	0.007	0.19	-10000	0	-0.89	9	9
IL5	-0.073	0.34	-10000	0	-0.91	39	39
IL2	0.01	0.2	-10000	0	-0.73	11	11
IL3	-0.027	0.046	-10000	0	-10000	0	0
RNF128	-0.083	0.24	-10000	0	-0.58	77	77
NFATC1	-0.032	0.28	-10000	0	-0.74	40	40
CDK4	0.008	0.17	0.57	12	-10000	0	12
PTPRK	0.029	0.12	-10000	0	-0.73	4	4
IL8	-0.081	0.35	-10000	0	-0.91	40	40
POU2F1	0.01	0.001	-10000	0	-10000	0	0

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.01	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.04	0.076	-10000	0	-0.26	19	19
NT3 (dimer)/TRKC	-0.09	0.17	-10000	0	-0.4	90	90
NT3 (dimer)/TRKB	-0.13	0.17	-10000	0	-0.33	153	153
SHC/Grb2/SOS1/GAB1/PI3K	0.029	0.013	-10000	0	-10000	0	0
RAPGEF1	0.01	0	-10000	0	-10000	0	0
BDNF	-0.23	0.26	-10000	0	-0.5	186	186
PIK3CA	0.01	0	-10000	0	-10000	0	0
DYNLT1	0.01	0	-10000	0	-10000	0	0
NTRK1	-0.014	0.11	-10000	0	-0.5	18	18
NTRK2	-0.16	0.24	-10000	0	-0.5	134	134
NTRK3	-0.091	0.2	-10000	0	-0.5	77	77
NT-4/5 (dimer)/TRKB	-0.12	0.17	-10000	0	-0.33	149	149
neuron apoptosis	0.2	0.2	0.49	102	-10000	0	102
SHC 2-3/Grb2	-0.21	0.22	-10000	0	-0.54	102	102
SHC1	0.01	0	-10000	0	-10000	0	0
SHC2	-0.13	0.14	-10000	0	-0.42	51	51
SHC3	-0.22	0.27	-10000	0	-0.64	98	98
STAT3 (dimer)	0.012	0.038	-10000	0	-0.33	5	5
NT3 (dimer)/TRKA	-0.042	0.11	-10000	0	-0.32	51	51
RIN/GDP	-0.023	0.077	-10000	0	-0.24	7	7
GIPC1	0.01	0	-10000	0	-10000	0	0
KRAS	0.01	0	-10000	0	-10000	0	0
DNAJA3	-0.027	0.071	-10000	0	-0.33	7	7
RIN/GTP	-0.002	0.027	-10000	0	-0.38	2	2
CCND1	0.015	0.084	-10000	0	-0.73	5	5
MAGED1	0.008	0.027	-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)	-0.018	0.12	-10000	0	-0.5	21	21
SHC/GRB2/SOS1	0	0	-10000	0	-10000	0	0
GRB2	0.01	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.05	0.12	-10000	0	-0.34	59	59
TRKA/NEDD4-2	-0.016	0.074	-10000	0	-0.36	18	18
ELMO1	0.005	0.052	-10000	0	-0.51	4	4
RhoG/GTP/ELMO1/DOCK1	-0.003	0.03	-10000	0	-0.3	4	4
NGF	-0.03	0.14	-10000	0	-0.51	30	30
HRAS	0.01	0	-10000	0	-10000	0	0
DOCK1	0.01	0	-10000	0	-10000	0	0
GAB2	0.005	0.051	-10000	0	-0.5	4	4
RIT2	-0.002	0.037	-10000	0	-0.52	2	2
RIT1	0.01	0	-10000	0	-10000	0	0
FRS2	0.007	0.038	-10000	0	-0.52	2	2
DNM1	0.003	0.059	-10000	0	-0.52	5	5
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	-0.029	0.076	-10000	0	-0.34	10	10
mol:GDP	-0.033	0.11	-10000	0	-0.31	13	13
NGF (dimer)	-0.03	0.14	-10000	0	-0.51	30	30
RhoG/GDP	-0.004	0.037	-10000	0	-0.36	4	4
RIT1/GDP	-0.018	0.076	-10000	0	-0.22	9	9
TIAM1	0.001	0.068	-10000	0	-0.5	7	7
PIK3R1	0.01	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.24	0.2	-10000	0	-0.37	253	253
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2	-0.002	0.022	-10000	0	-0.3	2	2
SHC/GRB2/SOS1/GAB1	-0.001	0.013	-10000	0	-10000	0	0
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.023	0.12	-10000	0	-0.5	25	25
RAP1/GDP	-0.031	0.053	-10000	0	-0.24	1	1
KIDINS220/CRKL	0.01	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.23	0.26	-10000	0	-0.5	186	186
ubiquitin-dependent protein catabolic process	-0.036	0.099	-10000	0	-0.3	47	47
Schwann cell development	-0.045	0.034	-10000	0	-10000	0	0
EHD4	0.01	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	-0.001	0.019	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.029	0.023	-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	-0.23	0.21	-10000	0	-0.51	121	121
ABL1	0.01	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
Rap1/GTP	-0.085	0.072	-10000	0	-0.28	1	1
STAT3	0.012	0.038	-10000	0	-0.32	5	5
axon guidance	-0.22	0.2	-10000	0	-0.48	121	121
MAPK3	-0.022	0.12	-10000	0	-0.3	59	59
MAPK1	-0.022	0.12	-10000	0	-0.36	23	23
CDC42/GDP	-0.018	0.076	-10000	0	-0.22	7	7
NTF3	-0.023	0.12	-10000	0	-0.5	25	25
NTF4	-0.018	0.12	-10000	0	-0.5	21	21
NGF (dimer)/TRKA/FAIM	-0.036	0.1	-10000	0	-0.3	47	47
PI3K	0	0	-10000	0	-10000	0	0
FRS3	0.01	0	-10000	0	-10000	0	0
FAIM	0.01	0	-10000	0	-10000	0	0
GAB1	0.009	0.026	-10000	0	-0.5	1	1
RASGRF1	-0.13	0.14	-10000	0	-0.43	35	35
SOS1	0.01	0	-10000	0	-10000	0	0
MCF2L	-0.061	0.16	-10000	0	-0.33	92	92
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	-0.018	0.076	-10000	0	-0.22	7	7
NGF (dimer)/TRKA/GRIT	-0.037	0.1	-10000	0	-0.31	47	47
neuron projection morphogenesis	-0.002	0.081	-10000	0	-0.45	2	2
NGF (dimer)/TRKA/NEDD4-2	-0.036	0.1	-10000	0	-0.3	47	47
MAP2K1	0.031	0.013	-10000	0	-10000	0	0
NGFR	-0.007	0.093	-10000	0	-0.51	13	13
NGF (dimer)/TRKA/GIPC/GAIP	0.002	0.074	-10000	0	-0.36	1	1
RAS family/GTP/PI3K	0.025	0	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	-0.001	0.018	-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	0.006	0.045	-10000	0	-0.5	3	3
MAPKKK cascade	-0.088	0.17	-10000	0	-0.65	29	29
RASA1	0.01	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.016	0.074	-10000	0	-0.36	18	18
SQSTM1	0.008	0.027	-10000	0	-0.52	1	1
BDNF (dimer)/TRKB/GIPC	-0.21	0.18	-10000	0	-0.52	69	69
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.032	0.086	-10000	0	-0.5	2	2
MATK	-0.015	0.11	-10000	0	-0.5	19	19
NEDD4L	0.01	0	-10000	0	-10000	0	0
RAS family/GDP	-0.026	0.048	-10000	0	-0.23	1	1
NGF (dimer)/TRKA	-0.03	0.077	-10000	0	-0.35	7	7
Rac1/GTP	-0.086	0.098	-10000	0	-0.3	38	38
FRS2 family/SHP2/CRK family	-0.001	0.018	-10000	0	-10000	0	0

×

ErbB4 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
ErbB4/ErbB4/HBEGF/HBEGF	-0.07	0.14	-10000	0	-0.42	29	29
epithelial cell differentiation	-0.074	0.12	-10000	0	-0.44	14	14
ITCH	0.023	0.018	-10000	0	-10000	0	0
WWP1	-0.018	0.068	-10000	0	-10000	0	0
FYN	0.009	0.026	-10000	0	-0.5	1	1
EGFR	-0.007	0.093	-10000	0	-0.51	13	13
PRL	-0.01	0.082	-10000	0	-0.52	10	10
neuron projection morphogenesis	-0.022	0.11	-10000	0	-0.4	1	1
PTPRZ1	-0.12	0.23	-10000	0	-0.51	99	99
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.063	0.1	-10000	0	-0.44	1	1
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.063	0.13	-10000	0	-0.37	39	39
ADAM17	0.023	0.018	-10000	0	-10000	0	0
ErbB4/ErbB4	-0.032	0.089	-10000	0	-0.38	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.14	0.17	-10000	0	-0.41	70	70
NCOR1	0.01	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.074	0.11	-10000	0	-0.35	39	39
GRIN2B	-0.056	0.13	-10000	0	-0.51	5	5
ErbB4/ErbB2/betacellulin	-0.034	0.063	-10000	0	-0.34	10	10
STAT1	0.01	0	-10000	0	-10000	0	0
HBEGF	-0.073	0.19	-10000	0	-0.5	64	64
PRLR	-0.054	0.17	-10000	0	-0.51	48	48
E4ICDs/ETO2	-0.045	0.12	-10000	0	-0.42	17	17
axon guidance	0.006	0.076	-10000	0	-10000	0	0
NEDD4	0.021	0.031	-10000	0	-0.48	1	1
Prolactin receptor/Prolactin receptor/Prolactin	-0.054	0.13	-10000	0	-0.38	57	57
CBFA2T3	-0.029	0.14	-10000	0	-0.5	30	30
ErbB4/ErbB2/HBEGF	-0.067	0.1	-10000	0	-0.34	30	30
MAPK3	-0.029	0.11	-10000	0	-0.41	1	1
STAT1 (dimer)	-0.023	0.074	-10000	0	-0.32	1	1
MAPK1	-0.029	0.11	-10000	0	-0.41	1	1
JAK2	0.009	0.026	-10000	0	-0.5	1	1
ErbB4/ErbB2/neuregulin 1 beta	-0.074	0.12	-10000	0	-0.34	41	41
NRG1	-0.048	0.15	-10000	0	-0.35	76	76
NRG3	-0.19	0.25	-10000	0	-0.5	154	154
NRG2	-0.052	0.17	-10000	0	-0.5	47	47
NRG4	-0.038	0.15	-10000	0	-0.52	35	35
heart development	0.006	0.076	-10000	0	-10000	0	0
neural crest cell migration	-0.074	0.11	-10000	0	-0.34	41	41
ERBB2	0.024	0.03	-10000	0	-0.37	2	2
WWOX/E4ICDs	-0.023	0.074	-10000	0	-0.33	1	1
SHC1	0.01	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.069	0.11	-10000	0	-0.4	21	21
apoptosis	0.2	0.22	0.44	154	-10000	0	154
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.058	0.13	-10000	0	-0.4	26	26
ErbB4/ErbB2/epiregulin	-0.1	0.13	-10000	0	-0.35	49	49
ErbB4/ErbB4/betacellulin/betacellulin	-0.031	0.094	-10000	0	-0.4	10	10
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.1	0.14	-10000	0	-0.53	14	14
MDM2	-0.022	0.078	-10000	0	-0.33	1	1
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.067	0.11	-10000	0	-0.32	39	39
STAT5A	0.012	0.072	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.082	0.12	-10000	0	-0.36	44	44
DLG4	0.01	0	-10000	0	-10000	0	0
GRB2/SHC	0	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.039	0.055	-10000	0	-10000	0	0
STAT5A (dimer)	-0.078	0.12	-10000	0	-0.47	14	14
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.01	0.068	-10000	0	-10000	0	0
LRIG1	0.007	0.036	-10000	0	-0.5	2	2
EREG	-0.15	0.24	-10000	0	-0.51	119	119
BTC	-0.005	0.084	-10000	0	-0.5	11	11
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.003	0.074	-10000	0	-10000	0	0
ERBB4	-0.032	0.089	-10000	0	-0.38	1	1
STAT5B	0.01	0	-10000	0	-10000	0	0
YAP1	-0.002	0.027	-10000	0	-0.53	1	1
GRB2	0.01	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.049	0.085	-10000	0	-0.34	16	16
glial cell differentiation	0.039	0.055	-10000	0	-10000	0	0
WWOX	0.01	0	-10000	0	-10000	0	0
cell proliferation	-0.062	0.15	-10000	0	-0.44	26	26

×

Aurora A 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	-0.015	0.072	-9999	-0.3	2	2
BIRC5	-0.3	0.26	-9999	-0.52	233	233
NFKBIA	-0.011	0.07	-9999	-10000	0	0
CPEB1	-0.065	0.18	-9999	-0.5	57	57
AKT1	-0.011	0.07	-9999	-10000	0	0
NDEL1	0.01	0	-9999	-10000	0	0
Aurora A/BRCA1	-0.019	0.062	-9999	-0.41	1	1
NDEL1/TACC3	-0.014	0.057	-9999	-0.39	1	1
GADD45A	0.007	0.037	-9999	-0.51	2	2
GSK3B	0.011	0.004	-9999	-10000	0	0
PAK1/Aurora A	-0.013	0.069	-9999	-10000	0	0
MDM2	0.007	0.038	-9999	-0.52	2	2
JUB	0.007	0.036	-9999	-0.5	2	2
TPX2	-0.2	0.19	-9999	-0.37	223	223
TP53	-0.008	0.043	-9999	-10000	0	0
DLG7	-0.019	0.069	-9999	-10000	0	0
AURKAIP1	0.01	0	-9999	-10000	0	0
ARHGEF7	0.01	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	-0.015	0.061	-9999	-0.41	1	1
G2/M transition of mitotic cell cycle	-0.019	0.061	-9999	-0.41	1	1
AURKA	-0.022	0.085	-9999	-10000	0	0
AURKB	-0.059	0.055	-9999	-0.13	78	78
CDC25B	-0.014	0.055	-9999	-0.22	1	1
G2/M transition checkpoint	-0.02	0.062	-9999	-0.33	2	2
mRNA polyadenylation	-0.059	0.12	-9999	-0.3	57	57
Aurora A/CPEB	-0.059	0.12	-9999	-0.3	57	57
Aurora A/TACC1/TRAP/chTOG	-0.02	0.075	-9999	-0.37	5	5
BRCA1	0.008	0.027	-9999	-0.52	1	1
centrosome duplication	-0.013	0.069	-9999	-10000	0	0
regulation of centrosome cycle	-0.014	0.056	-9999	-0.38	1	1
spindle assembly	-0.02	0.074	-9999	-0.36	5	5
TDRD7	0.01	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.17	0.15	-9999	-0.37	81	81
CENPA	-0.055	0.054	-9999	-0.14	78	78
Aurora A/PP2A	-0.013	0.069	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.002	0.052	-9999	-10000	0	0
negative regulation of DNA binding	0	0.046	-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	-0.02	0.063	-9999	-0.33	2	2
mitotic prometaphase	0.016	0.015	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.022	0.085	-9999	-10000	0	0
TACC1	-0.011	0.1	-9999	-0.5	16	16
TACC3	0.008	0.027	-9999	-0.52	1	1
Aurora A/Antizyme1	-0.014	0.058	-9999	-10000	0	0
Aurora A/RasGAP	-0.013	0.069	-9999	-10000	0	0
OAZ1	0.01	0	-9999	-10000	0	0
RAN	0.007	0.038	-9999	-0.52	2	2
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.011	0.004	-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	-0.2	0.19	-9999	-0.37	223	223
PPP2R5D	0.01	0	-9999	-10000	0	0
Aurora A/TPX2	-0.17	0.18	-9999	-0.32	223	223
PAK1	0.01	0	-9999	-10000	0	0
CKAP5	0.01	0	-9999	-10000	0	0

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.011	0.068	-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	0.006	0.046	-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	-0.035	0.13	-10000	0	-0.29	68	68
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	0.012	0.057	-10000	0	-0.36	1	1
NICD/RBPSUH	-0.007	0.061	-10000	0	-0.54	5	5
WIF1	-0.34	0.24	-10000	0	-0.5	269	269
NOTCH1	-0.008	0.064	-10000	0	-0.57	5	5
PSENEN	0.009	0.027	-10000	0	-0.52	1	1
KREMEN2	-0.12	0.23	-10000	0	-0.52	95	95
DKK1	-0.12	0.23	-10000	0	-0.51	99	99
beta catenin/beta TrCP1	0.019	0.053	-10000	0	-10000	0	0
APH1B	0.009	0.026	-10000	0	-0.5	1	1
APH1A	0.01	0	-10000	0	-10000	0	0
AXIN1	-0.006	0.028	-10000	0	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	-0.022	0.058	0.28	1	-10000	0	1
PSEN1	0.01	0	-10000	0	-10000	0	0
FOS	-0.029	0.14	-10000	0	-0.5	30	30
JUN	0.007	0.036	-10000	0	-0.5	2	2
MAP3K7	0.009	0.002	-10000	0	-10000	0	0
CTNNB1	0.014	0.057	-10000	0	-10000	0	0
MAPK3	0.01	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.12	0.19	-10000	0	-0.36	135	135
HNF1A	-0.088	0.2	-10000	0	-0.52	72	72
CTBP1	0.009	0.002	-10000	0	-10000	0	0
MYC	0.014	0.096	-10000	0	-1.3	2	2
NKD1	-0.054	0.17	-10000	0	-0.5	49	49
FZD1	0.01	0	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.009	0.064	-10000	0	-0.54	5	5
apoptosis	-0.035	0.13	-10000	0	-0.29	68	68
Delta 1/NOTCHprecursor	-0.011	0.067	-10000	0	-0.54	5	5
DLL1	0.001	0.068	-10000	0	-0.5	7	7
PPARD	0.02	0.013	-10000	0	-10000	0	0
Gamma Secretase	-0.001	0.017	-10000	0	-10000	0	0
APC	-0.006	0.028	-10000	0	-10000	0	0
DVL1	-0.032	0.035	-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	-0.15	0.19	-10000	0	-0.36	162	162
LRP6	0.01	0	-10000	0	-10000	0	0
CSNK1A1	0.01	0.001	-10000	0	-10000	0	0
NLK	0.011	0.006	-10000	0	-10000	0	0
CCND1	0.005	0.15	-10000	0	-1.3	5	5
WNT1	0	0.07	-10000	0	-0.52	7	7
Axin1/APC/beta catenin	0.012	0.043	-10000	0	-0.28	1	1
DKK2	-0.081	0.2	-10000	0	-0.5	70	70
NOTCH1 precursor/DVL1	-0.018	0.061	-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	-0.009	0.064	-10000	0	-0.54	5	5
PPP2R5D	0.016	0.086	0.24	49	-0.2	1	50
MAPK1	0.01	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.18	0.12	-10000	0	-0.53	4	4
RBPJ	0.01	0	-10000	0	-10000	0	0
CREBBP	0.013	0.002	-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	-0.68	12	12
CRP	-0.15	0.23	-10000	0	-0.63	19	19
cell cycle arrest	-0.17	0.25	-10000	0	-0.57	69	69
TIMP1	-0.11	0.2	-10000	0	-0.57	16	16
IL6ST	-0.007	0.081	-10000	0	-0.5	10	10
Rac1/GDP	-0.065	0.14	-10000	0	-0.4	17	17
AP1	-0.002	0.095	-10000	0	-0.59	3	3
GAB2	0.007	0.052	-10000	0	-0.5	4	4
TNFSF11	-0.19	0.25	-10000	0	-0.64	38	38
HSP90B1	-0.004	0.044	-10000	0	-10000	0	0
GAB1	0.01	0.026	-10000	0	-0.5	1	1
MAPK14	-0.039	0.13	-10000	0	-0.5	9	9
AKT1	0.037	0.032	-10000	0	-10000	0	0
FOXO1	0.042	0.03	-10000	0	-10000	0	0
MAP2K6	-0.058	0.13	-10000	0	-0.43	14	14
mol:GTP	-0.002	0.002	-10000	0	-10000	0	0
MAP2K4	-0.078	0.16	-10000	0	-0.48	13	13
MITF	-0.064	0.13	-10000	0	-0.32	48	48
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	-0.075	0.34	-10000	0	-1.3	28	28
CEBPB	0.015	0.003	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	-0.009	0.082	0.22	2	-0.56	3	5
STAT3	-0.17	0.26	-10000	0	-0.59	69	69
STAT1	-0.002	0.011	-10000	0	-10000	0	0
CEBPD	-0.14	0.24	-10000	0	-0.79	11	11
PIK3CA	0.011	0	-10000	0	-10000	0	0
PI3K	0.004	0.007	-10000	0	-10000	0	0
JUN	0.007	0.036	-10000	0	-0.5	2	2
PIAS3/MITF	-0.056	0.12	-10000	0	-0.42	10	10
MAPK11	-0.041	0.13	-10000	0	-0.52	10	10
STAT3 (dimer)/FOXO1	-0.11	0.23	-10000	0	-0.66	22	22
GRB2/SOS1/GAB family	-0.055	0.11	0.18	2	-0.44	13	15
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.06	0.15	-10000	0	-0.33	56	56
GRB2	0.011	0.003	-10000	0	-10000	0	0
JAK2	0.009	0.026	-10000	0	-0.5	1	1
LBP	-0.13	0.21	-10000	0	-0.55	22	22
PIK3R1	0.011	0	-10000	0	-10000	0	0
JAK1	0.009	0.004	-10000	0	-10000	0	0
MYC	-0.14	0.23	-10000	0	-0.68	15	15
FGG	-0.33	0.46	-10000	0	-0.99	122	122
macrophage differentiation	-0.17	0.25	-10000	0	-0.57	69	69
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.068	0.12	-10000	0	-0.41	6	6
JUNB	-0.14	0.22	-10000	0	-0.65	17	17
FOS	-0.029	0.14	-10000	0	-0.5	30	30
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.072	0.14	-10000	0	-0.32	58	58
STAT1/PIAS1	-0.076	0.13	-10000	0	-0.33	47	47
GRB2/SOS1/GAB family/SHP2/PI3K	0.018	0.037	-10000	0	-0.26	1	1
STAT3 (dimer)	-0.17	0.26	-10000	0	-0.59	69	69
PRKCD	-0.094	0.18	-10000	0	-0.56	12	12
IL6R	-0.004	0.081	-10000	0	-0.51	10	10
SOCS3	-0.027	0.14	-10000	0	-0.86	4	4
gp130 (dimer)/JAK1/JAK1/LMO4	0.005	0.053	-10000	0	-0.3	10	10
Rac1/GTP	-0.096	0.12	-10000	0	-0.35	48	48
HCK	-0.011	0.1	-10000	0	-0.5	16	16
MAPKKK cascade	0.009	0.082	-10000	0	-0.59	4	4
bone resorption	-0.18	0.24	-10000	0	-0.61	38	38
IRF1	-0.14	0.22	-10000	0	-0.63	17	17
mol:GDP	-0.067	0.14	-10000	0	-0.33	50	50
SOS1	0.011	0.006	-10000	0	-10000	0	0
VAV1	-0.068	0.14	-10000	0	-0.34	51	51
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.035	0.13	-10000	0	-0.44	15	15
PTPN11	-0.001	0.01	-10000	0	-10000	0	0
IL6/IL6RA	-0.083	0.16	-10000	0	-0.37	96	96
gp130 (dimer)/TYK2/TYK2/LMO4	0.003	0.051	-10000	0	-0.3	10	10
gp130 (dimer)/JAK2/JAK2/LMO4	0.002	0.053	-10000	0	-0.3	11	11
IL6	-0.11	0.21	-10000	0	-0.5	88	88
PIAS3	0.01	0	-10000	0	-10000	0	0
PTPRE	0.012	0.038	-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	-0.062	0.12	-10000	0	-0.28	70	70
LMO4	0.006	0.008	-10000	0	-10000	0	0
STAT3 (dimer)/PIAS3	-0.19	0.21	-10000	0	-0.56	63	63
MCL1	0.042	0.029	-10000	0	-10000	0	0

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.13	0.39	-10000	0	-1.2	25	25
IL23A	-0.16	0.43	-10000	0	-1.3	29	29
NF kappa B1 p50/RelA/I kappa B alpha	-0.21	0.34	-10000	0	-1.1	36	36
positive regulation of T cell mediated cytotoxicity	-0.15	0.44	-10000	0	-1.2	36	36
ITGA3	-0.14	0.4	-10000	0	-1.2	27	27
IL17F	-0.071	0.27	-10000	0	-0.74	23	23
IL12B	0.011	0.06	-10000	0	-0.53	4	4
STAT1 (dimer)	-0.14	0.42	-10000	0	-1.2	35	35
CD4	-0.13	0.4	-10000	0	-1.2	24	24
IL23	-0.16	0.41	-10000	0	-1.2	29	29
IL23R	-0.001	0.083	-10000	0	-10000	0	0
IL1B	-0.17	0.46	-10000	0	-1.4	33	33
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.13	0.38	-10000	0	-1.1	28	28
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	-0.011	0.1	-10000	0	-0.5	16	16
IL12RB1	-0.004	0.091	-10000	0	-0.53	11	11
PIK3CA	0.01	0	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	-0.001	0.07	-10000	0	-0.39	11	11
IL23R/JAK2	0.001	0.1	-10000	0	-10000	0	0
positive regulation of chronic inflammatory response	-0.15	0.44	-10000	0	-1.2	36	36
natural killer cell activation	0.001	0.007	0.036	1	-10000	0	1
JAK2	0.015	0.036	-10000	0	-0.5	1	1
PIK3R1	0.01	0	-10000	0	-10000	0	0
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	-0.15	0.39	-10000	0	-1.1	29	29
ALOX12B	-0.15	0.4	-10000	0	-1.1	33	33
CXCL1	-0.14	0.42	-10000	0	-1.2	32	32
T cell proliferation	-0.15	0.44	-10000	0	-1.2	36	36
NFKBIA	0.009	0.003	-10000	0	-10000	0	0
IL17A	-0.049	0.23	-10000	0	-0.59	16	16
PI3K	-0.2	0.35	-10000	0	-1.1	36	36
IFNG	-0.007	0.031	-10000	0	-0.11	5	5
STAT3 (dimer)	-0.2	0.33	-10000	0	-1.1	34	34
IL18R1	-0.011	0.1	-10000	0	-0.5	16	16
IL23/IL23R/JAK2/TYK2/SOCS3	-0.06	0.24	-10000	0	-0.72	15	15
IL18/IL18R	-0.017	0.11	-10000	0	-0.35	33	33
macrophage activation	-0.014	0.016	-10000	0	-0.045	22	22
TNF	-0.16	0.46	-10000	0	-1.4	33	33
STAT3/STAT4	-0.2	0.35	-10000	0	-1.1	36	36
STAT4 (dimer)	-0.14	0.42	-10000	0	-1.2	35	35
IL18	-0.001	0.072	-10000	0	-0.5	8	8
IL19	-0.13	0.39	-10000	0	-1.1	28	28
STAT5A (dimer)	-0.14	0.42	-10000	0	-1.2	35	35
STAT1	0.01	0	-10000	0	-10000	0	0
SOCS3	0.007	0.036	-10000	0	-0.5	2	2
CXCL9	-0.15	0.41	-10000	0	-1.2	31	31
MPO	-0.13	0.4	-10000	0	-1.2	28	28
positive regulation of humoral immune response	-0.15	0.44	-10000	0	-1.2	36	36
IL23/IL23R/JAK2/TYK2	-0.16	0.47	-10000	0	-1.3	35	35
IL6	-0.28	0.57	-10000	0	-1.2	97	97
STAT5A	0.009	0.026	-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	0.036	1	-10000	0	1
CD3E	-0.13	0.39	-10000	0	-1.2	27	27
keratinocyte proliferation	-0.15	0.44	-10000	0	-1.2	36	36
NOS2	-0.18	0.47	-10000	0	-1.2	53	53

×

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	-0.14	0.23	-9999	-0.5	112	112
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.01	0	-9999	-10000	0	0
TCEB1	0.007	0.038	-9999	-0.52	2	2
HIF1A/p53	0.004	0.036	-9999	-10000	0	0
HIF1A	-0.002	0.037	-9999	-10000	0	0
COPS5	0.01	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	-0.001	0.018	-9999	-10000	0	0
FIH (dimer)	0.01	0	-9999	-10000	0	0
CDKN2A	-0.14	0.24	-9999	-0.52	115	115
ARNT/IPAS	-0.1	0.16	-9999	-0.35	112	112
HIF1AN	0.01	0	-9999	-10000	0	0
GNB2L1	0.01	0	-9999	-10000	0	0
HIF1A/ARNT	0.004	0.036	-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	-0.002	0.022	-9999	-0.3	2	2
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.004	0.036	-9999	-10000	0	0
PHD1-3/OS9	-0.073	0.12	-9999	-0.27	105	105
HIF1A/RACK1/Elongin B/Elongin C	-0.012	0.025	-9999	-0.28	1	1
VHL	0.01	0	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
HIF1A/JAB1	0.004	0.036	-9999	-10000	0	0
EGLN3	-0.13	0.24	-9999	-0.52	106	106
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	0.024	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	115	115

×

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	0.003	0.052	-9999	-0.5	4	4
PDGF/PDGFRA/CRKL	-0.004	0.034	-9999	-0.34	4	4
positive regulation of JUN kinase activity	-0.002	0.024	-9999	-10000	0	0
CRKL	0.01	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.084	0.15	-9999	-0.36	91	91
AP1	-0.07	0.23	-9999	-0.87	30	30
mol:IP3	0.013	0.041	-9999	-0.35	4	4
PLCG1	0.013	0.041	-9999	-0.35	4	4
PDGF/PDGFRA/alphaV Integrin	-0.004	0.034	-9999	-0.34	4	4
RAPGEF1	0.01	0	-9999	-10000	0	0
CRK	0.01	0	-9999	-10000	0	0
mol:Ca2+	0.013	0.041	-9999	-0.35	4	4
CAV3	-0.11	0.21	-9999	-0.5	87	87
CAV1	-0.3	0.25	-9999	-0.5	241	241
SHC/Grb2/SOS1	-0.002	0.024	-9999	-10000	0	0
PDGF/PDGFRA/Shf	-0.006	0.043	-9999	-0.35	6	6
FOS	-0.035	0.24	-9999	-0.86	30	30
JUN	-0.007	0.03	-9999	-0.36	2	2
oligodendrocyte development	-0.004	0.034	-9999	-0.34	4	4
GRB2	0.01	0	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
mol:DAG	0.013	0.041	-9999	-0.35	4	4
PDGF/PDGFRA	0.003	0.052	-9999	-0.5	4	4
actin cytoskeleton reorganization	-0.005	0.039	-9999	-0.35	5	5
SRF	0.018	0.007	-9999	-10000	0	0
SHC1	0.01	0	-9999	-10000	0	0
PI3K	-0.003	0.028	-9999	-0.28	4	4
PDGF/PDGFRA/Crk/C3G	-0.003	0.028	-9999	-0.28	4	4
JAK1	0.014	0.037	-9999	-0.34	4	4
ELK1/SRF	0.026	0.031	-9999	-10000	0	0
SHB	0.009	0.026	-9999	-0.5	1	1
SHF	0.007	0.038	-9999	-0.52	2	2
CSNK2A1	0.005	0.014	-9999	-10000	0	0
GO:0007205	0.013	0.044	-9999	-0.38	4	4
SOS1	0.01	0	-9999	-10000	0	0
Ras protein signal transduction	-0.002	0.024	-9999	-10000	0	0
PDGF/PDGFRA/SHB	-0.005	0.039	-9999	-0.35	5	5
PDGF/PDGFRA/Caveolin-1	-0.22	0.18	-9999	-0.37	242	242
ITGAV	0.01	0	-9999	-10000	0	0
ELK1	0.017	0.043	-9999	-0.32	4	4
PIK3CA	0.01	0	-9999	-10000	0	0
PDGF/PDGFRA/Crk	-0.004	0.034	-9999	-0.34	4	4
JAK-STAT cascade	0.014	0.037	-9999	-0.34	4	4
cell proliferation	-0.006	0.043	-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	0.026	0.025	-9999	-10000	0	0
VDR	0.007	0.037	-9999	-0.51	2	2
FAM120B	0.01	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.091	0.14	-9999	-0.46	12	12
RXRs/LXRs/DNA/Oxysterols	-0.076	0.15	-9999	-0.48	22	22
MED1	0.01	0	-9999	-10000	0	0
mol:9cRA	0.002	0.011	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	0.004	0.078	-9999	-0.46	1	1
RXRs/NUR77	-0.17	0.18	-9999	-0.47	52	52
RXRs/PPAR	-0.13	0.16	-9999	-0.43	43	43
NCOR2	0.01	0	-9999	-10000	0	0
VDR/VDR/Vit D3	-0.002	0.026	-9999	-0.37	2	2
RARs/VDR/DNA/Vit D3	-0.002	0.025	-9999	-0.24	4	4
RARA	0.01	0	-9999	-10000	0	0
NCOA1	0.01	0	-9999	-10000	0	0
VDR/VDR/DNA	0.007	0.037	-9999	-0.51	2	2
RARs/RARs/DNA/9cRA	-0.001	0.018	-9999	-0.25	2	2
RARG	0.01	0	-9999	-10000	0	0
RPS6KB1	0.042	0.04	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	0.004	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	0.026	-9999	-0.37	2	2
RXRs/PPAR/9cRA/PGJ2/DNA	-0.12	0.15	-9999	-0.37	12	12
NR1H4	-0.032	0.14	-9999	-0.52	28	28
RXRs/LXRs/DNA	-0.093	0.14	-9999	-0.39	12	12
NR1H2	0.013	0.008	-9999	-10000	0	0
NR1H3	0.013	0.009	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.11	0.14	-9999	-0.32	14	14
NR4A1	-0.092	0.2	-9999	-0.5	78	78
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.095	0.12	-9999	-0.31	26	26
RXRG	-0.24	0.26	-9999	-0.5	197	197
RXR alpha/CCPG	0.009	0.009	-9999	-10000	0	0
RXRA	0.013	0.008	-9999	-10000	0	0
RXRB	0.012	0.009	-9999	-10000	0	0
THRB	-0.04	0.15	-9999	-0.5	38	38
PPARG	-0.059	0.18	-9999	-0.5	53	53
PPARD	0.01	0	-9999	-10000	0	0
TNF	-0.098	0.25	-9999	-1.1	22	22
mol:Oxysterols	0.003	0.01	-9999	-10000	0	0
cholesterol transport	-0.075	0.15	-9999	-0.48	22	22
PPARA	0.01	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	0.007	0.036	-9999	-0.5	2	2
RXRs/NUR77/BCL2	-0.15	0.16	-9999	-0.26	237	237
SREBF1	-0.063	0.14	-9999	-0.53	12	12
RXRs/RXRs/DNA/9cRA	-0.12	0.15	-9999	-0.37	12	12
ABCA1	-0.063	0.14	-9999	-0.53	12	12
RARs/THRs	-0.024	0.074	-9999	-0.49	1	1
RXRs/FXR	-0.13	0.16	-9999	-0.44	26	26
BCL2	0.007	0.038	-9999	-0.52	2	2

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	0.014	0.11	0.5	18	-10000	0	18
PI3K Class IB/PDE3B	-0.014	0.11	-10000	0	-0.5	18	18
PDE3B	-0.014	0.11	-10000	0	-0.5	18	18

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.009	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.035	0.089	-10000	0	-0.27	51	51
regulation of S phase of mitotic cell cycle	-0.007	0.083	-10000	0	-0.23	49	49
GNAO1	0.005	0.052	-10000	0	-0.51	4	4
HRAS	0.01	0.001	-10000	0	-10000	0	0
SHBG/T-DHT	-0.001	0.023	-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	-0.32	10	10
T-DHT/AR	-0.046	0.12	-10000	0	-0.36	50	50
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.002	-10000	0	-0.007	30	30
GNAI2	0.01	0	-10000	0	-10000	0	0
GNAI3	0.01	0	-10000	0	-10000	0	0
GNAI1	0.007	0.036	-10000	0	-0.5	2	2
mol:GDP	-0.05	0.13	-10000	0	-0.39	49	49
cell proliferation	-0.004	0.14	-10000	0	-0.42	30	30
PIK3CA	0.01	0	-10000	0	-10000	0	0
FOS	-0.029	0.22	-10000	0	-0.79	30	30
mol:Ca2+	-0.011	0.022	-10000	0	-0.066	38	38
MAPK3	-0.001	0.12	-10000	0	-0.45	10	10
MAPK1	0.003	0.07	-10000	0	-0.26	10	10
PIK3R1	0.01	0	-10000	0	-10000	0	0
mol:IP3	0	0.001	-10000	0	-0.004	30	30
cAMP biosynthetic process	0.008	0.03	-10000	0	-0.31	2	2
GNG2	0.009	0.026	-10000	0	-0.5	1	1
potassium channel inhibitor activity	0	0.001	-10000	0	-0.004	30	30
HRAS/GTP	-0.032	0.08	-10000	0	-0.29	10	10
actin cytoskeleton reorganization	0	0	-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	30	30
PI3K	0	0	-10000	0	-10000	0	0
apoptosis	0.005	0.13	0.42	30	-10000	0	30
T-DHT/AR/PELP1	-0.038	0.1	-10000	0	-0.3	50	50
HRAS/GDP	-0.046	0.12	-10000	0	-0.37	49	49
CREB1	-0.007	0.14	-10000	0	-0.46	30	30
RAC1-CDC42/GTP	0	0	-10000	0	-10000	0	0
AR	-0.056	0.17	-10000	0	-0.5	50	50
GNB1	0.01	0	-10000	0	-10000	0	0
RAF1	-0.004	0.089	-10000	0	-0.3	10	10
RAC1-CDC42/GDP	-0.043	0.12	-10000	0	-0.35	49	49
T-DHT/AR/PELP1/Src	-0.034	0.09	-10000	0	-0.27	50	50
MAP2K2	0.001	0.09	-10000	0	-0.32	10	10
T-DHT/AR/PELP1/Src/PI3K	-0.008	0.084	-10000	0	-0.23	49	49
GNAZ	-0.036	0.15	-10000	0	-0.5	35	35
SHBG	0.006	0.038	-10000	0	-0.52	2	2
Gi family/GNB1/GNG2/GDP	0.004	0.081	-10000	0	-0.43	3	3
mol:T-DHT	0	0.001	-10000	0	-0.003	20	20
RAC1	0.01	0	-10000	0	-10000	0	0
GNRH1	0.005	0.037	-10000	0	-0.36	4	4
Gi family/GTP	-0.036	0.085	-10000	0	-0.35	15	15
CDC42	0.01	0	-10000	0	-10000	0	0

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.034	0.13	-9999	-0.47	14	14
FZD6	0.009	0.026	-9999	-0.5	1	1
WNT6	-0.021	0.12	-9999	-0.52	22	22
WNT4	-0.024	0.13	-9999	-0.5	26	26
FZD3	0.008	0.027	-9999	-0.52	1	1
WNT5A	0.003	0.057	-9999	-0.5	5	5
WNT11	-0.062	0.18	-9999	-0.5	55	55

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.009	0.026	-9999	-0.5	1	1
PLK4	-0.021	0.12	-9999	-0.52	23	23
regulation of centriole replication	-0.005	0.092	-9999	-0.37	24	24

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	-0.009	0.035	-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	0.007	0.038	-10000	0	-0.52	2	2
VHL/Elongin B/Elongin C/HIF2A	-0.068	0.12	-10000	0	-0.39	27	27
EPO	-0.036	0.22	-10000	0	-0.65	11	11
FIH (dimer)	0.01	0.012	-10000	0	-10000	0	0
APEX1	0.011	0.012	-10000	0	-10000	0	0
SERPINE1	-0.059	0.26	-10000	0	-0.7	23	23
FLT1	-0.007	0.034	-10000	0	-10000	0	0
ADORA2A	-0.053	0.25	-10000	0	-0.64	22	22
germ cell development	-0.067	0.26	-10000	0	-0.65	26	26
SLC11A2	-0.055	0.25	-10000	0	-0.66	22	22
BHLHE40	-0.055	0.25	-10000	0	-0.66	22	22
HIF1AN	0.01	0.012	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.09	0.14	-10000	0	-0.45	33	33
ETS1	0.022	0.003	-10000	0	-10000	0	0
CITED2	-0.009	0.053	-10000	0	-0.96	1	1
KDR	-0.027	0.17	-10000	0	-1.2	8	8
PGK1	-0.055	0.25	-10000	0	-0.65	24	24
SIRT1	0.01	0	-10000	0	-10000	0	0
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	-0.059	0.29	-10000	0	-0.76	25	25
EPAS1	-0.049	0.17	-10000	0	-0.37	50	50
SP1	0.016	0.001	-10000	0	-10000	0	0
ABCG2	-0.082	0.3	-10000	0	-0.73	39	39
EFNA1	-0.056	0.26	-10000	0	-0.66	24	24
FXN	-0.053	0.25	-10000	0	-0.64	22	22
POU5F1	-0.071	0.27	-10000	0	-0.68	26	26
neuron apoptosis	0.069	0.28	0.73	26	-10000	0	26
EP300	0.01	0	-10000	0	-10000	0	0
EGLN3	-0.13	0.24	-10000	0	-0.53	106	106
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	-0.002	0.022	-10000	0	-0.3	2	2
VHL	0.01	0	-10000	0	-10000	0	0
ARNT	0.011	0.012	-10000	0	-10000	0	0
SLC2A1	-0.14	0.32	-10000	0	-0.68	57	57
TWIST1	-0.096	0.3	-10000	0	-0.68	45	45
ELK1	0.016	0.005	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.088	0.14	-10000	0	-0.45	31	31
VEGFA	-0.055	0.25	-10000	0	-0.66	22	22
CREBBP	0.01	0	-10000	0	-10000	0	0

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.01	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.031	0.075	-9999	-10000	0	0
Syndecan-3/Neurocan	-0.007	0.042	-9999	-0.26	11	11
POMC	-0.017	0.11	-9999	-0.51	20	20
EGFR	-0.007	0.093	-9999	-0.51	13	13
Syndecan-3/EGFR	-0.008	0.044	-9999	-0.24	13	13
AGRP	-0.2	0.25	-9999	-0.5	156	156
NCSTN	0.01	0	-9999	-10000	0	0
PSENEN	0.008	0.027	-9999	-0.52	1	1
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.009	0.026	-9999	-0.5	1	1
APH1A	0.01	0	-9999	-10000	0	0
NCAN	-0.008	0.087	-9999	-0.52	11	11
long-term memory	-0.001	0.011	-9999	-10000	0	0
Syndecan-3/IL8	-0.013	0.055	-9999	-0.25	20	20
PSEN1	0.01	0	-9999	-10000	0	0
Src/Cortactin	0	0	-9999	-10000	0	0
FYN	0.009	0.026	-9999	-0.5	1	1
limb bud formation	0	0.004	-9999	-10000	0	0
MC4R	-0.032	0.14	-9999	-0.52	29	29
SRC	0.01	0	-9999	-10000	0	0
PTN	-0.065	0.18	-9999	-0.5	57	57
FGFR/FGF/Syndecan-3	0	0.004	-9999	-10000	0	0
neuron projection morphogenesis	-0.036	0.083	-9999	-0.44	3	3
Syndecan-3/AgRP	-0.095	0.12	-9999	-0.24	156	156
Syndecan-3/AgRP/MC4R	-0.11	0.13	-9999	-0.45	14	14
Fyn/Cortactin	-0.001	0.018	-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	-0.013	0.054	-9999	-0.25	20	20
IL8	-0.017	0.12	-9999	-0.52	20	20
Syndecan-3/Fyn/Cortactin	-0.001	0.012	-9999	-10000	0	0
Syndecan-3/CASK	0	0.004	-9999	-10000	0	0
alpha-MSH/MC4R	-0.045	0.13	-9999	-0.38	46	46
Gamma Secretase	-0.001	0.017	-9999	-10000	0	0

×

Regulation of Androgen receptor activity

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
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	0.093	-9999	-0.47	3	3
JUN	0.007	0.036	-9999	-0.5	2	2
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	0.005	0.073	-9999	-0.37	14	14
FOXO1	0.01	0	-9999	-10000	0	0
T-DHT/AR	0.02	0.099	-9999	-0.5	3	3
MAP2K6	-0.009	0.098	-9999	-0.52	14	14
BRM/BAF57	-0.003	0.031	-9999	-0.35	3	3
MAP2K4	0.01	0.004	-9999	-10000	0	0
SMARCA2	0.006	0.045	-9999	-0.5	3	3
PDE9A	-0.049	0.18	-9999	-1.2	7	7
NCOA2	0.007	0.036	-9999	-0.5	2	2
CEBPA	-0.02	0.12	-9999	-0.5	23	23
EHMT2	0.01	0.001	-9999	-10000	0	0
cell proliferation	0.018	0.14	-9999	-0.45	17	17
NR0B1	-0.11	0.21	-9999	-0.52	82	82
EGR1	-0.028	0.13	-9999	-0.5	29	29
RXRs/9cRA	-0.13	0.13	-9999	-0.26	197	197
AR/RACK1/Src	-0.001	0.068	-9999	-0.37	3	3
AR/GR	-0.005	0.096	-9999	-0.3	20	20
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	-0.002	0.07	-9999	-0.38	3	3
SRC	0.023	0.058	-9999	-0.32	2	2
NR3C1	0.01	0	-9999	-10000	0	0
KLK3	-0.065	0.1	-9999	-0.45	6	6
APPBP2	0.01	0.004	-9999	-10000	0	0
TRIM24	0.01	0.001	-9999	-10000	0	0
T-DHT/AR/TIP60	0.014	0.072	-9999	-0.4	3	3
TMPRSS2	-0.11	0.31	-9999	-1.1	34	34
RXRG	-0.25	0.26	-9999	-0.5	197	197
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	0.015	0.098	-9999	-0.41	6	6
AR	-0.01	0.11	-9999	-0.34	21	21
SENP1	0.01	0	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
MDM2	0.007	0.038	-9999	-0.52	2	2
SRY	0.001	0.004	-9999	-10000	0	0
GATA2	-0.037	0.15	-9999	-0.5	36	36
MYST2	0.01	0	-9999	-10000	0	0
HOXB13	-0.18	0.25	-9999	-0.52	136	136
T-DHT/AR/RACK1/Src	0.019	0.071	-9999	-0.38	3	3
positive regulation of transcription	-0.037	0.15	-9999	-0.5	36	36
DNAJA1	0.01	0.004	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.023	0.01	-9999	-10000	0	0
NCOA1	0.012	0.003	-9999	-10000	0	0
SPDEF	-0.17	0.25	-9999	-0.52	134	134
T-DHT/AR/TIF2	0.028	0.051	-9999	-10000	0	0
T-DHT/AR/Hsp90	0.014	0.072	-9999	-0.4	3	3
GSK3B	0.01	0.003	-9999	-10000	0	0
NR2C1	0.01	0	-9999	-10000	0	0
mol:T-DHT	0.018	0.062	-9999	-0.32	5	5
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	-0.062	0.13	-9999	-0.38	28	28
CREBBP	0.01	0	-9999	-10000	0	0
SMARCE1	0.01	0.001	-9999	-10000	0	0

×

Syndecan-2-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
Syndecan-2/Fibronectin	0.014	0.046	-9999	-0.34	6	6
EPHB2	-0.053	0.17	-9999	-0.52	47	47
Syndecan-2/TACI	-0.01	0.092	-9999	-0.3	35	35
LAMA1	-0.021	0.12	-9999	-0.51	23	23
Syndecan-2/alpha2 ITGB1	-0.06	0.11	-9999	-0.34	14	14
HRAS	0.01	0	-9999	-10000	0	0
Syndecan-2/CASK	-0.002	0.026	-9999	-0.3	3	3
ITGA5	0.007	0.037	-9999	-0.51	2	2
BAX	0.03	0.024	-9999	-10000	0	0
EPB41	0.01	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.002	0.023	-9999	-0.26	3	3
LAMA3	-0.097	0.21	-9999	-0.5	82	82
EZR	0.01	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.088	0.2	-9999	-0.5	75	75
Syndecan-2/MMP2	0.016	0.032	-9999	-0.3	4	4
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.013	0.068	-9999	-0.37	14	14
dendrite morphogenesis	-0.022	0.11	-9999	-0.3	50	50
Syndecan-2/GM-CSF	-0.009	0.09	-9999	-0.3	35	35
determination of left/right symmetry	0.013	0.032	-9999	-0.35	3	3
Syndecan-2/PKC delta	0.017	0.027	-9999	-0.29	3	3
GNB2L1	0.01	0	-9999	-10000	0	0
MAPK3	0	0.081	-9999	-0.26	35	35
MAPK1	0	0.081	-9999	-0.26	35	35
Syndecan-2/RACK1	-0.002	0.021	-9999	-0.24	3	3
NF1	0.01	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.013	0.032	-9999	-0.35	3	3
ITGA2	-0.009	0.098	-9999	-0.52	14	14
MAPK8	0.025	0.027	-9999	-0.29	3	3
Syndecan-2/alpha2/beta1 Integrin	-0.025	0.083	-9999	-0.51	4	4
Syndecan-2/Kininogen	-0.016	0.085	-9999	-0.31	31	31
ITGB1	0.01	0	-9999	-10000	0	0
SRC	0.027	0.022	-9999	-0.22	3	3
Syndecan-2/CASK/Protein 4.1	-0.002	0.023	-9999	-0.26	3	3
extracellular matrix organization	0.017	0.027	-9999	-0.29	3	3
actin cytoskeleton reorganization	0.014	0.046	-9999	-0.34	6	6
Syndecan-2/Caveolin-2/Ras	-0.052	0.1	-9999	-0.26	78	78
Syndecan-2/Laminin alpha3	-0.049	0.13	-9999	-0.29	85	85
Syndecan-2/RasGAP	-0.002	0.02	-9999	-0.23	3	3
alpha5/beta1 Integrin	-0.002	0.026	-9999	-0.36	2	2
PRKCD	0.01	0	-9999	-10000	0	0
Syndecan-2 dimer	-0.022	0.11	-9999	-0.31	50	50
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	-0.52	32	32
RASA1	0.01	0	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.013	0.068	-9999	-0.37	14	14
Syndecan-2/Synbindin	0.017	0.027	-9999	-0.29	3	3
TGFB1	0.01	0	-9999	-10000	0	0
CASP3	0.024	0.025	-9999	-0.26	3	3
FN1	0.005	0.051	-9999	-0.5	4	4
Syndecan-2/IL8	0	0.076	-9999	-0.3	23	23
SDC2	0.013	0.032	-9999	-0.35	3	3
KNG1	-0.033	0.14	-9999	-0.52	28	28
Syndecan-2/Neurofibromin	0.017	0.027	-9999	-0.29	3	3
TRAPPC4	0.01	0	-9999	-10000	0	0
CSF2	-0.032	0.14	-9999	-0.5	32	32
Syndecan-2/TGFB1	0.017	0.027	-9999	-0.29	3	3
Syndecan-2/Syntenin/PI-4-5-P2	-0.002	0.023	-9999	-0.26	3	3
Syndecan-2/Ezrin	-0.002	0.022	-9999	-0.26	3	3
PRKACA	0.024	0.025	-9999	-0.26	3	3
angiogenesis	0	0.076	-9999	-0.3	23	23
MMP2	0.008	0.027	-9999	-0.52	1	1
IL8	-0.017	0.12	-9999	-0.52	20	20
calcineurin-NFAT signaling pathway	-0.01	0.091	-9999	-0.3	35	35

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.01	0.052	-9999	-0.48	4	4
Syndecan-4/Syndesmos	-0.019	0.085	-9999	-0.53	2	2
positive regulation of JNK cascade	-0.05	0.082	-9999	-0.37	10	10
Syndecan-4/ADAM12	-0.11	0.16	-9999	-0.38	67	67
CCL5	0.005	0.051	-9999	-0.5	4	4
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0.01	0	-9999	-10000	0	0
ITGA5	0.007	0.037	-9999	-0.51	2	2
SDCBP	0.01	0	-9999	-10000	0	0
PLG	-0.009	0.08	-9999	-0.53	9	9
ADAM12	-0.19	0.26	-9999	-0.52	146	146
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	-0.033	0.049	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.033	0.1	-9999	-0.41	11	11
Syndecan-4/CXCL12/CXCR4	-0.038	0.095	-9999	-0.47	4	4
Syndecan-4/Laminin alpha3	-0.07	0.13	-9999	-0.37	28	28
MDK	-0.16	0.25	-9999	-0.52	126	126
Syndecan-4/FZD7	-0.019	0.086	-9999	-0.47	3	3
Syndecan-4/Midkine	-0.1	0.15	-9999	-0.39	44	44
FZD7	0.009	0.026	-9999	-0.5	1	1
Syndecan-4/FGFR1/FGF	-0.065	0.1	-9999	-0.48	7	7
THBS1	0.007	0.036	-9999	-0.5	2	2
integrin-mediated signaling pathway	-0.039	0.11	-9999	-0.41	11	11
positive regulation of MAPKKK cascade	-0.05	0.082	-9999	-0.37	10	10
Syndecan-4/TACI	-0.039	0.11	-9999	-0.39	19	19
CXCR4	0.01	0	-9999	-10000	0	0
cell adhesion	0.004	0.042	-9999	-0.33	4	4
Syndecan-4/Dynamin	-0.019	0.085	-9999	-0.53	2	2
Syndecan-4/TSP1	-0.02	0.09	-9999	-0.64	2	2
Syndecan-4/GIPC	-0.019	0.085	-9999	-0.53	2	2
Syndecan-4/RANTES	-0.021	0.087	-9999	-0.53	2	2
ITGB1	0.01	0	-9999	-10000	0	0
LAMA1	-0.021	0.12	-9999	-0.51	23	23
LAMA3	-0.097	0.21	-9999	-0.5	82	82
RAC1	0.01	0	-9999	-10000	0	0
PRKCA	0.014	0.042	-9999	-0.46	2	2
Syndecan-4/alpha-Actinin	-0.019	0.085	-9999	-0.53	2	2
TFPI	-0.01	0.098	-9999	-0.5	15	15
F2	-0.069	0.18	-9999	-0.52	54	54
alpha5/beta1 Integrin	-0.002	0.026	-9999	-0.36	2	2
positive regulation of cell adhesion	-0.076	0.14	-9999	-0.44	12	12
ACTN1	0.01	0	-9999	-10000	0	0
TNC	-0.034	0.15	-9999	-0.52	33	33
Syndecan-4/CXCL12	-0.034	0.1	-9999	-0.41	10	10
FGF6	0	0.001	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
CXCL12	-0.021	0.12	-9999	-0.5	24	24
TNFRSF13B	-0.033	0.14	-9999	-0.52	32	32
FGF2	-0.054	0.17	-9999	-0.5	49	49
FGFR1	0.006	0.045	-9999	-0.51	3	3
Syndecan-4/PI-4-5-P2	-0.025	0.085	-9999	-0.53	2	2
mol:GDP	0	0	-9999	-10000	0	0
FN1	0.006	0.05	-9999	-0.49	4	4
cell migration	-0.014	0.021	-9999	-10000	0	0
PRKCD	0.011	0.006	-9999	-10000	0	0
vasculogenesis	-0.019	0.087	-9999	-0.6	2	2
SDC4	-0.026	0.089	-9999	-0.56	2	2
Syndecan-4/Tenascin C	-0.04	0.11	-9999	-0.42	11	11
Syndecan-4/PI-4-5-P2/PKC alpha	-0.026	0.039	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.019	0.085	-9999	-0.53	2	2
MMP9	-0.082	0.2	-9999	-0.52	68	68
Rac1/GTP	0.004	0.043	-9999	-0.34	4	4
cytoskeleton organization	-0.018	0.083	-9999	-0.51	2	2
GIPC1	0.01	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.028	0.098	-9999	-0.47	5	5

×

Coregulation of Androgen receptor activity

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
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	19	19
T-DHT/AR/Ubc9	-0.044	0.11	-9999	-0.33	50	50
CARM1	0.01	0	-9999	-10000	0	0
PRDX1	0.008	0.027	-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	0.007	0.036	-9999	-0.5	2	2
MED1	0.01	0.002	-9999	-10000	0	0
MAK	-0.01	0.095	-9999	-0.5	14	14
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	0.005	0.051	-9999	-0.5	4	4
GSN	0.01	0.001	-9999	-10000	0	0
NCOA2	0.007	0.036	-9999	-0.5	2	2
NCOA6	0.01	0.001	-9999	-10000	0	0
DNA-PK	0.001	0.008	-9999	-10000	0	0
NCOA4	0.01	0	-9999	-10000	0	0
PIAS3	0.01	0.001	-9999	-10000	0	0
cell proliferation	-0.036	0.13	-9999	-0.74	13	13
XRCC5	0.01	0.001	-9999	-10000	0	0
UBE3A	0.01	0.003	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.053	0.13	-9999	-0.33	60	60
FHL2	-0.067	0.13	-9999	-0.45	13	13
RANBP9	0.01	0.001	-9999	-10000	0	0
JMJD1A	-0.001	0.042	-9999	-0.13	38	38
CDK6	0.007	0.037	-9999	-0.51	2	2
TGFB1I1	0.007	0.036	-9999	-0.5	2	2
T-DHT/AR/CyclinD1	-0.048	0.12	-9999	-0.33	54	54
XRCC6	0.01	0.001	-9999	-10000	0	0
T-DHT/AR	-0.039	0.14	-9999	-0.34	58	58
CTDSP1	0.01	0.001	-9999	-10000	0	0
CTDSP2	0.01	0.004	-9999	-10000	0	0
BRCA1	0.009	0.027	-9999	-0.52	1	1
TCF4	0.007	0.036	-9999	-0.5	2	2
CDKN2A	-0.14	0.24	-9999	-0.52	115	115
SRF	0.004	0.028	-9999	-10000	0	0
NKX3-1	-0.047	0.13	-9999	-0.92	5	5
KLK3	0.017	0.046	-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	0.003	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.047	0.11	-9999	-0.33	51	51
AR	-0.063	0.18	-9999	-0.52	50	50
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	-0.032	0.11	-9999	-0.3	50	50
RPS6KA3	0.01	0.001	-9999	-10000	0	0
T-DHT/AR/ARA70	-0.044	0.11	-9999	-0.33	50	50
LATS2	0.01	0.002	-9999	-10000	0	0
T-DHT/AR/PRX1	-0.034	0.11	-9999	-0.3	50	50
Cyclin D3/CDK11 p58	0	0	-9999	-10000	0	0
VAV3	0.003	0.058	-9999	-0.51	5	5
KLK2	-0.041	0.089	-9999	-0.38	19	19
CASP8	0.009	0.026	-9999	-0.5	1	1
T-DHT/AR/TIF2/CARM1	-0.035	0.1	-9999	-0.29	52	52
TMPRSS2	-0.1	0.28	-9999	-0.98	34	34
CCND1	0.003	0.057	-9999	-0.5	5	5
PIAS1	0.01	0.003	-9999	-10000	0	0
mol:T-DHT	-0.008	0.027	-9999	-0.081	27	27
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.01	0.005	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.047	0.11	-9999	-0.33	52	52
CMTM2	-0.089	0.2	-9999	-0.5	76	76
SNURF	-0.006	0.088	-9999	-0.5	12	12
ZMIZ1	0.004	0.024	-9999	-10000	0	0
CCND3	0.01	0	-9999	-10000	0	0
TGIF1	0.01	0.002	-9999	-10000	0	0
FKBP4	0.009	0.027	-9999	-0.52	1	1

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	-0.01	0.061	-9999	-0.37	11	11
VLDLR	-0.002	0.076	-9999	-0.5	9	9
CRKL	0.01	0	-9999	-10000	0	0
LRPAP1	0.01	0	-9999	-10000	0	0
FYN	0.009	0.026	-9999	-0.5	1	1
ITGA3	0.006	0.045	-9999	-0.5	3	3
RELN/VLDLR/Fyn	-0.05	0.12	-9999	-0.31	63	63
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.001	0.012	-9999	-10000	0	0
AKT1	-0.012	0.094	-9999	-0.4	5	5
MAP2K7	0.01	0	-9999	-10000	0	0
RAPGEF1	0.01	0	-9999	-10000	0	0
DAB1	-0.002	0.065	-9999	-0.52	6	6
RELN/LRP8/DAB1	-0.05	0.11	-9999	-0.28	71	71
LRPAP1/LRP8	-0.009	0.058	-9999	-0.37	10	10
RELN/LRP8/DAB1/Fyn	-0.047	0.1	-9999	-0.36	5	5
DAB1/alpha3/beta1 Integrin	-0.047	0.099	-9999	-0.46	7	7
long-term memory	-0.097	0.14	-9999	-0.51	20	20
DAB1/LIS1	-0.047	0.1	-9999	-0.47	6	6
DAB1/CRLK/C3G	-0.045	0.096	-9999	-0.46	6	6
PIK3CA	0.01	0	-9999	-10000	0	0
DAB1/NCK2	-0.048	0.1	-9999	-0.48	6	6
ARHGEF2	0.01	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.094	0.21	-9999	-0.51	78	78
CDK5R1	-0.005	0.087	-9999	-0.52	11	11
RELN	-0.065	0.18	-9999	-0.5	57	57
PIK3R1	0.01	0	-9999	-10000	0	0
RELN/LRP8/Fyn	-0.051	0.11	-9999	-0.3	68	68
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.095	0.14	-9999	-0.52	16	16
MAPK8	0.01	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.049	0.11	-9999	-0.29	67	67
ITGB1	0.01	0	-9999	-10000	0	0
MAP1B	-0.031	0.12	-9999	-0.47	9	9
RELN/LRP8	-0.05	0.11	-9999	-0.3	67	67
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.053	0.11	-9999	-0.51	7	7
PI3K	0	0	-9999	-10000	0	0
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.003	0.031	-9999	-0.35	3	3
RAP1A	-0.006	0.11	-9999	-0.43	6	6
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	-0.011	0.082	-9999	-0.52	10	10
NCK2	0.01	0	-9999	-10000	0	0
neuron differentiation	0.003	0.069	-9999	-10000	0	0
neuron adhesion	0.003	0.1	-9999	-0.4	7	7
LRP8	-0.004	0.083	-9999	-0.52	10	10
GSK3B	-0.006	0.09	-9999	-0.41	4	4
RELN/VLDLR/DAB1/Fyn	-0.046	0.1	-9999	-0.5	5	5
MAP3K11	0.009	0.026	-9999	-0.5	1	1
RELN/VLDLR/DAB1/P13K	-0.02	0.1	-9999	-0.25	58	58
CDK5	0.01	0	-9999	-10000	0	0
MAPT	-0.021	0.12	-9999	-0.47	24	24
neuron migration	-0.007	0.12	-9999	-0.45	4	4
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	0.002	0.069	-9999	-10000	0	0
RELN/VLDLR	-0.05	0.11	-9999	-0.32	19	19

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.008	0.095	-9999	-0.5	14	14
GNB1/GNG2	-0.049	0.1	-9999	-0.42	14	14
mol:DAG	-0.012	0.11	-9999	-0.4	12	12
PLCG1	-0.012	0.11	-9999	-0.41	12	12
YES1	-0.025	0.12	-9999	-0.44	14	14
FZD3	0.008	0.027	-9999	-0.52	1	1
FZD6	0.009	0.026	-9999	-0.5	1	1
G protein	-0.045	0.095	-9999	-0.4	14	14
MAP3K7	-0.02	0.13	-9999	-0.39	25	25
mol:Ca2+	-0.011	0.1	-9999	-0.39	12	12
mol:IP3	-0.012	0.11	-9999	-0.4	12	12
NLK	-0.003	0.007	-9999	-10000	0	0
GNB1	0.01	0	-9999	-10000	0	0
CAMK2A	-0.028	0.14	-9999	-0.42	26	26
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.034	0.13	-9999	-0.47	14	14
CSNK1A1	0.01	0	-9999	-10000	0	0
GNAS	-0.025	0.12	-9999	-0.44	14	14
GO:0007205	-0.011	0.11	-9999	-0.39	12	12
WNT6	-0.021	0.12	-9999	-0.52	22	22
WNT4	-0.024	0.13	-9999	-0.5	26	26
NFAT1/CK1 alpha	-0.05	0.1	-9999	-0.43	14	14
GNG2	0.009	0.026	-9999	-0.5	1	1
WNT5A	0.003	0.057	-9999	-0.5	5	5
WNT11	-0.062	0.18	-9999	-0.5	55	55
CDC42	-0.018	0.11	-9999	-0.42	14	14

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	0.024	0.093	-10000	0	-0.36	9	9
TBX21	-0.007	0.34	-10000	0	-1.2	24	24
B2M	0.011	0.004	-10000	0	-10000	0	0
TYK2	0.018	0.015	-10000	0	-10000	0	0
IL12RB1	0.003	0.09	-10000	0	-0.52	11	11
GADD45B	0.019	0.26	-10000	0	-0.99	16	16
IL12RB2	-0.029	0.15	-10000	0	-0.51	35	35
GADD45G	0.018	0.27	-10000	0	-1	16	16
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	0.004	0.073	-10000	0	-0.5	8	8
IL2RA	-0.032	0.14	-10000	0	-0.52	31	31
IFNG	-0.035	0.15	-10000	0	-0.52	33	33
STAT3 (dimer)	0.027	0.23	-10000	0	-0.76	18	18
HLA-DRB5	-0.04	0.15	-10000	0	-0.5	38	38
FASLG	0.015	0.28	-10000	0	-1	18	18
NF kappa B2 p52/RelB	-0.08	0.22	-10000	0	-0.86	20	20
CD4	0	0.072	-10000	0	-0.5	8	8
SOCS1	0.01	0	-10000	0	-10000	0	0
EntrezGene:6955	0	0.008	-10000	0	-10000	0	0
CD3D	0.008	0.037	-10000	0	-0.51	2	2
CD3E	0.007	0.045	-10000	0	-0.5	3	3
CD3G	0.001	0.073	-10000	0	-0.51	8	8
IL12Rbeta2/JAK2	-0.006	0.12	-10000	0	-0.36	36	36
CCL3	0.017	0.27	-10000	0	-0.94	19	19
CCL4	0.018	0.27	-10000	0	-0.96	18	18
HLA-A	0.011	0.003	-10000	0	-10000	0	0
IL18/IL18R	0.018	0.12	-10000	0	-0.36	33	33
NOS2	-0.035	0.4	-10000	0	-1.2	38	38
IL12/IL12R/TYK2/JAK2/SPHK2	0.024	0.094	-10000	0	-0.36	9	9
IL1R1	0.019	0.27	-10000	0	-0.97	17	17
IL4	-0.004	0.017	-10000	0	-10000	0	0
JAK2	0.016	0.03	-10000	0	-0.5	1	1
EntrezGene:6957	0	0.007	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	0.015	0.17	-10000	0	-1.2	6	6
RAB7A	0.038	0.22	-10000	0	-0.81	12	12
lysosomal transport	0.04	0.21	-10000	0	-0.76	12	12
FOS	-0.056	0.36	-10000	0	-1.1	38	38
STAT4 (dimer)	0.036	0.25	-10000	0	-0.86	18	18
STAT5A (dimer)	-0.095	0.22	-10000	0	-0.82	25	25
GZMA	0.017	0.27	-10000	0	-1	16	16
GZMB	0.001	0.32	-10000	0	-1.1	22	22
HLX	0.003	0.058	-10000	0	-0.5	5	5
LCK	0.018	0.28	-10000	0	-0.96	20	20
TCR/CD3/MHC II/CD4	-0.021	0.16	-10000	0	-0.53	22	22
IL2/IL2R	-0.025	0.085	-10000	0	-0.29	35	35
MAPK14	0.025	0.27	-10000	0	-0.95	16	16
CCR5	0.019	0.26	-10000	0	-1	13	13
IL1B	-0.014	0.13	-10000	0	-0.51	24	24
STAT6	0.029	0.085	-10000	0	-0.25	7	7
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	0.056	-10000	0	-0.52	4	4
CD8A	0.004	0.058	-10000	0	-0.51	5	5
CD8B	0.002	0.069	-10000	0	-0.51	7	7
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.024	0.093	0.35	9	-10000	0	9
IL2RB	0.007	0.036	-10000	0	-0.5	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.04	0.23	-10000	0	-0.77	18	18
IL2RG	0.005	0.051	-10000	0	-0.5	4	4
IL12	0.02	0.067	-10000	0	-0.37	10	10
STAT5A	0.009	0.026	-10000	0	-0.5	1	1
CD247	0.004	0.058	-10000	0	-0.51	5	5
IL2	0.006	0.005	-10000	0	-10000	0	0
SPHK2	0.009	0.026	-10000	0	-0.5	1	1
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.01	0.066	-10000	0	-0.51	6	6
IL12/IL12R/TYK2/JAK2	0.013	0.31	-10000	0	-0.99	22	22
MAP2K3	0.022	0.27	-10000	0	-0.92	18	18
RIPK2	0.01	0	-10000	0	-10000	0	0
MAP2K6	0.02	0.27	-10000	0	-0.88	20	20
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.01	0.098	-10000	0	-0.5	15	15
IL18RAP	-0.007	0.1	-10000	0	-0.51	16	16
IL12Rbeta1/TYK2	0.015	0.07	-10000	0	-0.38	11	11
EOMES	-0.005	0.13	-10000	0	-1.2	4	4
STAT1 (dimer)	0.023	0.23	-10000	0	-0.74	19	19
T cell proliferation	0.033	0.21	-10000	0	-0.65	17	17
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.007	0.1	-10000	0	-0.5	16	16
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.075	0.18	-10000	0	-0.72	17	17
ATF2	0.033	0.25	-10000	0	-0.85	16	16

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.01	0	-9999	-10000	0	0
VLDLR	-0.002	0.076	-9999	-0.5	9	9
LRPAP1	0.01	0	-9999	-10000	0	0
NUDC	0.01	0	-9999	-10000	0	0
RELN/LRP8	-0.05	0.11	-9999	-0.3	67	67
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	-0.022	0.11	-9999	-0.26	67	67
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	-0.002	0.065	-9999	-0.52	6	6
IQGAP1	0.01	0	-9999	-10000	0	0
PLA2G7	-0.002	0.079	-9999	-0.52	9	9
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	-0.009	0.058	-9999	-0.37	10	10
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.01	0	-9999	-10000	0	0
CDK5R1	-0.005	0.087	-9999	-0.52	11	11
LIS1/Poliovirus Protein 3A	0	0	-9999	-10000	0	0
CDK5R2	-0.14	0.24	-9999	-0.52	113	113
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.054	0.12	-9999	-0.32	67	67
YWHAE	0.01	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.038	0.11	-9999	-0.33	22	22
MAP1B	-0.002	0.021	-9999	-0.28	1	1
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.015	0.1	-9999	-10000	0	0
RELN	-0.065	0.18	-9999	-0.5	57	57
PAFAH/LIS1	0.013	0.048	-9999	-0.3	9	9
LIS1/CLIP170	0.021	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.048	0.07	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.018	0.1	-9999	-0.41	8	8
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.047	0.12	-9999	-0.35	22	22
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	-0.018	0.12	-9999	-0.52	21	21
PAFAH1B2	0.01	0	-9999	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0.018	0.015	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.061	0.087	-9999	-0.31	22	22
LRP8	-0.004	0.083	-9999	-0.52	10	10
NDEL1/Katanin 60	-0.038	0.11	-9999	-0.33	22	22
P39/CDK5	-0.085	0.16	-9999	-0.48	22	22
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.021	0	-9999	-10000	0	0
CDK5	-0.013	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	-0.044	0.1	-9999	-0.5	5	5
RELN/VLDLR	-0.05	0.11	-9999	-0.32	19	19
CDC42	0	0	-9999	-10000	0	0

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.009	0.026	-9999	-0.5	1	1
alphaV beta3 Integrin	-0.023	0.089	-9999	-0.37	25	25
PTK2	-0.034	0.1	-9999	-0.4	23	23
positive regulation of JNK cascade	-0.018	0.068	-9999	-0.29	23	23
CDC42/GDP	0.017	0.1	-9999	-0.39	23	23
Rac1/GDP	0.018	0.1	-9999	-0.38	23	23
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	-0.022	0.083	-9999	-0.35	23	23
nectin-3/I-afadin	-0.022	0.085	-9999	-0.36	24	24
RAPGEF1	0.011	0.11	-9999	-0.43	23	23
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.004	0.12	-9999	-0.49	23	23
PDGFB-D/PDGFRB	0.009	0.026	-9999	-0.5	1	1
TLN1	0.005	0.086	-9999	-0.41	12	12
Rap1/GTP	-0.018	0.072	-9999	-0.3	23	23
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	-0.022	0.085	-9999	-0.36	24	24
PVR	0.01	0	-9999	-10000	0	0
Necl-5(dimer)	0.01	0	-9999	-10000	0	0
mol:GDP	0.012	0.12	-9999	-0.47	23	23
MLLT4	0.01	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
PI3K	-0.015	0.06	-9999	-0.49	1	1
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.01	0.061	-9999	-0.37	11	11
positive regulation of lamellipodium assembly	-0.019	0.073	-9999	-0.3	24	24
PVRL1	-0.005	0.087	-9999	-0.52	11	11
PVRL3	-0.021	0.12	-9999	-0.5	24	24
PVRL2	0.01	0	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
CDH1	0.007	0.036	-9999	-0.5	2	2
CLDN1	-0.012	0.1	-9999	-0.52	16	16
JAM-A/CLDN1	-0.027	0.087	-9999	-0.32	16	16
SRC	-0.035	0.13	-9999	-0.54	23	23
ITGB3	-0.024	0.13	-9999	-0.52	25	25
nectin-1(dimer)/I-afadin/I-afadin	-0.01	0.061	-9999	-0.37	11	11
FARP2	0.008	0.12	-9999	-0.46	23	23
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)	-0.018	0.07	-9999	-0.29	24	24
nectin-1/I-afadin	-0.01	0.061	-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	-0.026	0.087	-9999	-0.3	34	34
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0.009	0.026	-9999	-0.5	1	1
positive regulation of filopodium formation	-0.018	0.068	-9999	-0.29	23	23
alphaV/beta3 Integrin/Talin	0	0.1	-9999	-0.39	13	13
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	-0.001	0.091	-9999	-0.46	11	11
VAV2	0.006	0.12	-9999	-0.47	24	24
RAP1/GDP	-0.022	0.084	-9999	-0.36	23	23
ITGAV	0.01	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.018	0.07	-9999	-0.29	24	24
nectin-3(dimer)/I-afadin/I-afadin	-0.022	0.085	-9999	-0.36	24	24
Rac1/GTP	-0.023	0.088	-9999	-0.36	24	24
PTPRM	-0.023	0.095	-9999	-0.5	11	11
E-cadherin/beta catenin/alpha catenin	-0.008	0.041	-9999	-10000	0	0
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.01	0	-9999	-10000	0	0

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.001	0.015	-9999	-0.26	1	1
NF kappa B1 p50/RelA/I kappa B alpha	-0.026	0.07	-9999	-0.38	2	2
AP1	-0.042	0.091	-9999	-0.45	4	4
mol:PIP3	-0.029	0.073	-9999	-0.41	3	3
AKT1	-0.002	0.013	-9999	-10000	0	0
PTK2B	0.018	0.034	-9999	-0.27	2	2
RHOA	0.025	0.025	-9999	-10000	0	0
PIK3CB	0.01	0	-9999	-10000	0	0
mol:Ca2+	0.004	0.086	-9999	-0.38	3	3
MAGI3	0.003	0.057	-9999	-0.5	5	5
RELA	0.01	0	-9999	-10000	0	0
apoptosis	-0.006	0.085	-9999	-0.25	39	39
HRAS/GDP	0	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.013	0.068	-9999	-0.26	9	9
NF kappa B1 p50/RelA	-0.025	0.071	-9999	-0.38	2	2
endothelial cell migration	0.021	0.024	-9999	-0.44	1	1
ADCY4	0.01	0.07	-9999	-0.38	4	4
ADCY5	-0.005	0.089	-9999	-0.3	18	18
ADCY6	0.019	0.054	-9999	-0.35	1	1
ADCY7	0.019	0.054	-9999	-0.35	1	1
ADCY1	0.017	0.06	-9999	-0.31	4	4
ADCY2	0.004	0.076	-9999	-0.3	9	9
ADCY3	0.019	0.053	-9999	-0.35	1	1
ADCY8	-0.055	0.1	-9999	-0.3	17	17
ADCY9	0.015	0.065	-9999	-0.33	5	5
GSK3B	0.023	0.032	-9999	-0.25	2	2
arachidonic acid secretion	0.023	0.05	-9999	-0.32	1	1
GNG2	0.008	0.026	-9999	-0.5	1	1
TRIP6	0.018	0.028	-9999	-0.36	2	2
GNAO1	0.019	0.034	-9999	-0.3	4	4
HRAS	0.01	0	-9999	-10000	0	0
NFKBIA	0.011	0.097	-9999	-0.44	2	2
GAB1	0.009	0.026	-9999	-0.5	1	1
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.023	0.14	-9999	-0.84	11	11
JUN	0.007	0.036	-9999	-0.5	2	2
LPA/LPA2/NHERF2	-0.004	0.034	-9999	-0.3	5	5
TIAM1	-0.027	0.16	-9999	-0.98	11	11
PIK3R1	0.01	0	-9999	-10000	0	0
mol:IP3	0.003	0.088	-9999	-0.39	3	3
PLCB3	0.019	0.032	-9999	-0.26	5	5
FOS	-0.029	0.14	-9999	-0.5	30	30
positive regulation of mitosis	0.023	0.05	-9999	-0.32	1	1
LPA/LPA1-2-3	-0.029	0.082	-9999	-0.26	44	44
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.009	0.026	-9999	-0.5	1	1
stress fiber formation	0.016	0.052	-9999	-10000	0	0
GNAZ	-0.006	0.09	-9999	-0.29	35	35
EGFR/PI3K-beta/Gab1	-0.03	0.076	-9999	-0.43	3	3
positive regulation of dendritic cell cytokine production	-0.029	0.081	-9999	-0.26	44	44
LPA/LPA2/MAGI-3	-0.005	0.037	-9999	-0.3	6	6
ARHGEF1	0.03	0.016	-9999	-10000	0	0
GNAI2	0.022	0.011	-9999	-10000	0	0
GNAI3	0.022	0.011	-9999	-10000	0	0
GNAI1	0.02	0.025	-9999	-0.29	2	2
LPA/LPA3	-0.039	0.11	-9999	-0.36	43	43
LPA/LPA2	-0.001	0.019	-9999	-0.37	1	1
LPA/LPA1	-0.001	0.012	-9999	-0.24	1	1
HB-EGF/EGFR	-0.096	0.17	-9999	-0.32	133	133
HBEGF	-0.11	0.18	-9999	-0.37	128	128
mol:DAG	0.003	0.088	-9999	-0.39	3	3
cAMP biosynthetic process	0.005	0.063	-9999	-0.31	2	2
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	0.011	0.097	-9999	-0.44	2	2
GNAQ	-0.012	0.09	-9999	-0.26	44	44
LPAR2	0.008	0.027	-9999	-0.52	1	1
LPAR3	-0.046	0.16	-9999	-0.5	43	43
LPAR1	0.013	0.007	-9999	-10000	0	0
IL8	-0.041	0.14	-9999	-0.38	29	29
PTK2	0.001	0.085	-9999	-0.25	5	5
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.007	0.085	-9999	-0.25	39	39
EGFR	-0.008	0.093	-9999	-0.51	13	13
PLCG1	-0.009	0.099	-9999	-0.28	40	40
PLD2	0.001	0.085	-9999	-10000	0	0
G12/G13	0	0.008	-9999	-10000	0	0
PI3K-beta	-0.002	0.015	-9999	-10000	0	0
cell migration	-0.016	0.048	-9999	-0.25	11	11
SLC9A3R2	0.005	0.051	-9999	-0.5	4	4
PXN	0.016	0.053	-9999	-10000	0	0
HRAS/GTP	0.023	0.051	-9999	-0.32	1	1
RAC1	0.01	0	-9999	-10000	0	0
MMP9	-0.082	0.2	-9999	-0.52	68	68
PRKCE	0.004	0.052	-9999	-0.5	4	4
PRKCD	0.009	0.084	-9999	-0.36	3	3
Gi(beta/gamma)	0.021	0.053	-9999	-0.34	1	1
mol:LPA	0.003	0.008	-9999	-0.15	1	1
TRIP6/p130 Cas/FAK1/Paxillin	-0.023	0.064	-9999	-10000	0	0
MAPKKK cascade	0.023	0.05	-9999	-0.32	1	1
contractile ring contraction involved in cytokinesis	0.025	0.025	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.02	0.1	-9999	-0.27	54	54
GNA15	-0.011	0.086	-9999	-0.25	44	44
GNA12	0.01	0	-9999	-10000	0	0
GNA13	0.01	0	-9999	-10000	0	0
MAPT	0.013	0.069	-9999	-0.26	9	9
GNA11	-0.012	0.089	-9999	-0.26	44	44
Rac1/GTP	-0.025	0.15	-9999	-0.89	11	11
MMP2	0.021	0.024	-9999	-0.45	1	1

×

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

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
MAP4K1	0.018	0.1	-10000	0	-0.41	18	18
CRKL	0.015	0.099	-10000	0	-0.43	17	17
HRAS	0.028	0.1	-10000	0	-0.39	19	19
mol:PIP3	0.004	0.095	-10000	0	-0.42	17	17
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	-0.45	17	17
FOXO3	0.02	0.091	-10000	0	-0.39	17	17
AKT1	0.014	0.097	-10000	0	-0.42	17	17
BAD	0.02	0.091	-10000	0	-0.39	17	17
megakaryocyte differentiation	-0.012	0.13	-10000	0	-0.48	21	21
GSK3B	0.02	0.091	-10000	0	-0.39	17	17
RAF1	0.033	0.087	-10000	0	-0.38	8	8
SHC1	0.01	0	-10000	0	-10000	0	0
STAT3	0.01	0.1	-10000	0	-0.45	17	17
STAT1	0.007	0.22	-10000	0	-0.98	17	17
HRAS/SPRED1	-0.02	0.072	-10000	0	-0.38	8	8
cell proliferation	0.011	0.1	-10000	0	-0.44	17	17
PIK3CA	0.01	0	-10000	0	-10000	0	0
TEC	0.01	0	-10000	0	-10000	0	0
RPS6KB1	0.01	0.1	-10000	0	-0.46	17	17
HRAS/SPRED2	-0.02	0.072	-10000	0	-0.38	8	8
LYN/TEC/p62DOK	-0.02	0.088	-10000	0	-0.42	17	17
MAPK3	0.037	0.065	-10000	0	-0.27	7	7
STAP1	0.003	0.11	-10000	0	-0.44	19	19
GRAP2	-0.006	0.088	-10000	0	-0.5	12	12
JAK2	-0.041	0.18	-10000	0	-0.84	17	17
STAT1 (dimer)	0.008	0.21	-10000	0	-0.96	17	17
mol:Gleevec	-0.002	0.004	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.023	0.091	-10000	0	-0.42	18	18
actin filament polymerization	0.01	0.1	-10000	0	-0.44	17	17
LYN	0.01	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	0.011	0.14	-10000	0	-0.58	19	19
PIK3R1	0.01	0	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.019	0.08	-10000	0	-0.38	17	17
PI3K	-0.021	0.09	-10000	0	-0.43	17	17
PTEN	0.01	0	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	0.003	0.26	-10000	0	-1.2	17	17
MAPK8	0.01	0.1	-10000	0	-0.45	17	17
STAT3 (dimer)	0.011	0.1	-10000	0	-0.44	17	17
positive regulation of transcription	0.036	0.055	-10000	0	-0.22	7	7
mol:GDP	-0.025	0.093	-10000	0	-0.4	19	19
PIK3C2B	0.009	0.11	-10000	0	-0.47	17	17
CBL/CRKL	0.021	0.094	-10000	0	-0.4	17	17
FER	0.01	0.1	-10000	0	-0.45	17	17
SH2B3	0.009	0.1	-10000	0	-0.45	18	18
PDPK1	0.01	0.088	-10000	0	-0.38	17	17
SNAI2	0.007	0.11	-10000	0	-0.48	18	18
positive regulation of cell proliferation	0.012	0.16	-10000	0	-0.74	17	17
KITLG	0.008	0.055	-10000	0	-0.53	4	4
cell motility	0.012	0.16	-10000	0	-0.74	17	17
PTPN6	0.002	0.007	-10000	0	-10000	0	0
EPOR	0.03	0.064	-10000	0	-10000	0	0
STAT5A (dimer)	0.014	0.14	-10000	0	-0.62	17	17
SOCS1	0.01	0	-10000	0	-10000	0	0
cell migration	0.002	0.12	0.46	17	-10000	0	17
SOS1	0.01	0	-10000	0	-10000	0	0
EPO	0.004	0.047	-10000	0	-0.52	3	3
VAV1	0.003	0.057	-10000	0	-0.5	5	5
GRB10	0.01	0.1	-10000	0	-0.46	17	17
PTPN11	0.001	0.005	-10000	0	-10000	0	0
SCF/KIT	-0.013	0.1	-10000	0	-0.48	17	17
GO:0007205	-0.002	0.005	-10000	0	-10000	0	0
MAP2K1	0.037	0.07	-10000	0	-0.3	7	7
CBL	0.01	0	-10000	0	-10000	0	0
KIT	-0.013	0.26	-10000	0	-1.2	17	17
MAP2K2	0.037	0.07	-10000	0	-0.3	8	8
SHC/Grb2/SOS1	-0.02	0.088	-10000	0	-0.42	17	17
STAT5A	0.013	0.14	-10000	0	-0.64	17	17
GRB2	0.01	0	-10000	0	-10000	0	0
response to radiation	0.007	0.11	-10000	0	-0.47	18	18
SHC/GRAP2	-0.011	0.061	-10000	0	-0.35	12	12
PTPRO	-0.013	0.14	-10000	0	-0.49	21	21
SH2B2	0.01	0.1	-10000	0	-0.45	17	17
DOK1	0.01	0	-10000	0	-10000	0	0
MATK	-0.002	0.12	-10000	0	-0.47	17	17
CREBBP	0.029	0.007	-10000	0	-10000	0	0
BCL2	0.03	0.067	-10000	0	-10000	0	0

×

Caspase cascade in apoptosis

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
TOP1	0.006	0.082	-10000	0	-0.3	24	24
ACTA1	-0.004	0.1	-10000	0	-0.37	24	24
NUMA1	0.006	0.082	-10000	0	-0.3	24	24
SPTAN1	-0.001	0.1	-10000	0	-0.37	24	24
LIMK1	-0.001	0.1	-10000	0	-0.37	24	24
BIRC3	0.002	0.064	-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	0.001	0.092	-10000	0	-0.34	25	25
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.01	0	-10000	0	-10000	0	0
PTK2	0.006	0.082	-10000	0	-0.3	24	24
DIABLO	0.01	0	-10000	0	-10000	0	0
apoptotic nuclear changes	0	0.099	-10000	0	-0.36	24	24
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.008	0.027	-10000	0	-0.52	1	1
GSN	-0.001	0.1	-10000	0	-0.37	24	24
MADD	0.01	0	-10000	0	-10000	0	0
TFAP2A	-0.052	0.15	-10000	0	-0.66	22	22
BID	0.006	0.055	-10000	0	-0.2	25	25
MAP3K1	0.005	0.036	-10000	0	-0.2	4	4
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	-0.001	0.1	-10000	0	-0.37	24	24
CASP9	0.01	0	-10000	0	-10000	0	0
DNA repair	-0.003	0.028	-10000	0	-10000	0	0
neuron apoptosis	0.017	0.021	-10000	0	-0.3	1	1
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.005	0.097	-10000	0	-0.35	24	24
APAF1	0.01	0	-10000	0	-10000	0	0
CASP6	0.016	0.053	-10000	0	-0.42	1	1
TRAF2	0.01	0	-10000	0	-10000	0	0
ICAD/CAD	0.005	0.097	-10000	0	-0.35	24	24
CASP7	-0.004	0.031	0.29	2	-10000	0	2
KRT18	0.012	0.017	-10000	0	-10000	0	0
apoptosis	0.01	0.087	-10000	0	-0.3	24	24
DFFA	-0.001	0.1	-10000	0	-0.37	24	24
DFFB	-0.001	0.1	-10000	0	-0.37	24	24
PARP1	0.003	0.028	-10000	0	-10000	0	0
actin filament polymerization	-0.006	0.093	0.34	24	-10000	0	24
TNF	-0.02	0.12	-10000	0	-0.5	23	23
CYCS	0.009	0.039	-10000	0	-0.22	4	4
SATB1	0.017	0.066	-10000	0	-0.42	3	3
SLK	-0.001	0.1	-10000	0	-0.37	24	24
p15 BID/BAX	0.01	0.049	-10000	0	-0.28	4	4
CASP2	0.026	0.053	-10000	0	-0.34	1	1
JNK cascade	-0.005	0.036	0.2	4	-10000	0	4
CASP3	-0.007	0.11	-10000	0	-0.39	24	24
LMNB2	0.027	0.044	-10000	0	-0.36	1	1
RIPK1	0.01	0	-10000	0	-10000	0	0
CASP4	0.01	0	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	-0.004	0.033	-10000	0	-0.27	4	4
negative regulation of DNA binding	-0.051	0.15	-10000	0	-0.65	22	22
stress fiber formation	0	0.099	-10000	0	-0.36	24	24
GZMB	-0.008	0.1	-10000	0	-0.4	24	24
CASP1	0.011	0.029	-10000	0	-0.32	3	3
LMNB1	0.026	0.045	-10000	0	-0.39	1	1
APP	0.017	0.021	-10000	0	-0.3	1	1
TNFRSF1A	0.01	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.008	0.019	-10000	0	-0.36	1	1
VIM	0.005	0.085	-10000	0	-0.3	24	24
LMNA	0.027	0.044	-10000	0	-0.36	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.021	0.056	-10000	0	-0.36	1	1
LRDD	0.007	0.036	-10000	0	-0.5	2	2
SREBF1	-0.001	0.1	-10000	0	-0.37	24	24
APAF-1/Caspase 9	-0.002	0.016	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0.006	0.08	-10000	0	-0.29	24	24
CFL2	0.006	0.096	-10000	0	-0.34	24	24
GAS2	-0.016	0.12	-10000	0	-0.35	35	35
positive regulation of apoptosis	0.029	0.045	-10000	0	-0.37	1	1
PRF1	-0.01	0.098	-10000	0	-0.5	15	15

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.012	0.063	-9999	-0.33	14	14
EFNA5	0.001	0.069	-9999	-0.51	7	7
FYN	0.006	0.061	-9999	-0.29	15	15
neuron projection morphogenesis	-0.012	0.063	-9999	-0.33	14	14
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.012	0.063	-9999	-0.33	14	14
EPHA5	-0.004	0.074	-9999	-0.52	8	8

×

Signaling events mediated by PTP1B

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
PDGFRB	0.009	0.026	-10000	0	-0.5	1	1
Jak2/Leptin Receptor	-0.03	0.084	-10000	0	-0.37	13	13
PTP1B/AKT1	0.008	0.039	-10000	0	-10000	0	0
FYN	0.009	0.026	-10000	0	-0.5	1	1
p210 bcr-abl/PTP1B	0.004	0.043	-10000	0	-0.23	2	2
EGFR	-0.008	0.093	-10000	0	-0.51	13	13
EGF/EGFR	-0.053	0.093	-10000	0	-0.29	20	20
CSF1	0.006	0.045	-10000	0	-0.5	3	3
AKT1	0.01	0.001	-10000	0	-10000	0	0
INSR	0.01	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.022	0.094	-10000	0	-0.26	46	46
Insulin Receptor/Insulin	-0.007	0.022	-10000	0	-10000	0	0
HCK	-0.011	0.1	-10000	0	-0.5	16	16
CRK	0.01	0	-10000	0	-10000	0	0
TYK2	0.01	0.04	-10000	0	-0.23	1	1
EGF	-0.094	0.21	-10000	0	-0.51	78	78
YES1	0.01	0	-10000	0	-10000	0	0
CAV1	-0.091	0.1	-10000	0	-0.25	61	61
TXN	0.005	0.037	-10000	0	-0.51	2	2
PTP1B/IRS1/GRB2	-0.005	0.033	-10000	0	-0.3	1	1
cell migration	-0.004	0.043	0.23	2	-10000	0	2
STAT3	0.01	0.001	-10000	0	-10000	0	0
PRLR	-0.055	0.17	-10000	0	-0.51	48	48
ITGA2B	-0.047	0.16	-10000	0	-0.5	43	43
CSF1R	0.002	0.063	-10000	0	-0.5	6	6
Prolactin Receptor/Prolactin	-0.054	0.13	-10000	0	-0.38	57	57
FGR	-0.033	0.14	-10000	0	-0.5	33	33
PTP1B/p130 Cas	0.008	0.042	-10000	0	-0.26	2	2
Crk/p130 Cas	-0.005	0.033	-10000	0	-0.26	1	1
DOK1	0.015	0.04	-10000	0	-0.25	1	1
JAK2	-0.005	0.06	-10000	0	-0.3	8	8
Jak2/Leptin Receptor/Leptin	-0.027	0.06	-10000	0	-0.36	2	2
PIK3R1	0.01	0	-10000	0	-10000	0	0
PTPN1	0.004	0.043	-10000	0	-0.23	2	2
LYN	0.01	0	-10000	0	-10000	0	0
CDH2	-0.051	0.17	-10000	0	-0.52	45	45
SRC	0.014	0.018	-10000	0	-10000	0	0
ITGB3	-0.025	0.13	-10000	0	-0.52	25	25
CAT1/PTP1B	-0.03	0.13	-10000	0	-0.49	18	18
CAPN1	0.01	0.001	-10000	0	-10000	0	0
CSK	0.01	0	-10000	0	-10000	0	0
PI3K	-0.003	0.019	-10000	0	-10000	0	0
mol:H2O2	-0.001	0.002	-10000	0	-10000	0	0
STAT3 (dimer)	-0.022	0.058	-10000	0	-0.39	2	2
negative regulation of transcription	-0.005	0.06	-10000	0	-0.29	8	8
FCGR2A	0.002	0.063	-10000	0	-0.5	6	6
FER	0.008	0.004	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.062	0.14	-10000	0	-0.36	67	67
BLK	-0.06	0.18	-10000	0	-0.52	52	52
Insulin Receptor/Insulin/Shc	0	0	-10000	0	-10000	0	0
RHOA	0.01	0.001	-10000	0	-10000	0	0
LEPR	-0.025	0.13	-10000	0	-0.5	27	27
BCAR1	0.009	0.026	-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	-0.037	0.14	-10000	0	-0.54	18	18
PRL	-0.01	0.082	-10000	0	-0.52	10	10
SOCS3	0.005	0.09	-10000	0	-1.2	2	2
SPRY2	0.007	0.026	-10000	0	-0.5	1	1
Insulin Receptor/Insulin/IRS1	-0.001	0.015	-10000	0	-0.3	1	1
CSF1/CSF1R	-0.009	0.056	-10000	0	-0.38	5	5
Ras protein signal transduction	0.011	0.014	-10000	0	-10000	0	0
IRS1	0.009	0.026	-10000	0	-0.5	1	1
INS	0	0.001	-10000	0	-10000	0	0
LEP	-0.048	0.16	-10000	0	-0.52	42	42
STAT5B	0.002	0.044	-10000	0	-0.23	2	2
STAT5A	0.002	0.045	-10000	0	-0.23	3	3
GRB2	0.01	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.008	0.043	-10000	0	-0.29	1	1
CSN2	-0.014	0.044	-10000	0	-10000	0	0
PIK3CA	0.01	0	-10000	0	-10000	0	0
LAT	0.007	0.06	-10000	0	-0.45	6	6
YBX1	0.016	0.002	-10000	0	-10000	0	0
LCK	0.007	0.037	-10000	0	-0.51	2	2
SHC1	0.01	0	-10000	0	-10000	0	0
NOX4	-0.014	0.1	-10000	0	-0.52	16	16

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.01	0	-10000	0	-10000	0	0
HDAC4	0.008	0.027	-10000	0	-0.52	1	1
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.008	0.094	0.37	25	-10000	0	25
CDKN1A	-0.002	0.034	-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	-0.028	0.14	-10000	0	-0.52	28	28
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.007	0.033	-10000	0	-0.37	3	3
PPARGC1A	-0.11	0.22	-10000	0	-0.5	95	95
FHL2	-0.067	0.19	-10000	0	-0.52	57	57
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0	0.007	-10000	0	-10000	0	0
HIST2H4A	-0.008	0.094	-10000	0	-0.37	25	25
SIRT1/FOXO3a	0	0.007	-10000	0	-10000	0	0
SIRT1	0	0.009	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0	0.017	-10000	0	-0.31	1	1
SIRT1/Histone H1b	-0.01	0.033	-10000	0	-10000	0	0
apoptosis	0	0.007	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.072	0.13	-10000	0	-0.3	95	95
p53/SIRT1	0.001	0.019	0.38	1	-10000	0	1
SIRT1/FOXO4	0	0.007	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	-0.04	0.098	-10000	0	-0.28	57	57
HIST1H1E	0.004	0.045	-10000	0	-10000	0	0
SIRT1/p300	0	0.007	-10000	0	-10000	0	0
muscle cell differentiation	0.002	0.027	0.3	3	-10000	0	3
TP53	0	0.009	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0	0.007	-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	-0.026	0.095	-10000	0	-0.37	28	28
ACSS2	0.015	0.02	-10000	0	-0.36	1	1
SIRT1/PCAF/MYOD	-0.002	0.028	-10000	0	-0.31	3	3

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.001	0.016	-10000	0	-10000	0	0
RFC1	0.001	0.016	-10000	0	-10000	0	0
PRKDC	0.001	0.016	-10000	0	-10000	0	0
RIPK1	0.011	0.004	-10000	0	-10000	0	0
CASP7	-0.016	0.036	-10000	0	-0.38	1	1
FASLG/FAS/FADD/FAF1	0.008	0.075	0.2	31	-0.26	7	38
MAP2K4	-0.023	0.13	-10000	0	-0.42	7	7
mol:ceramide	-0.007	0.089	-10000	0	-0.36	8	8
GSN	0.001	0.016	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 8	0.013	0.078	-10000	0	-0.34	7	7
FAS	0.003	0.052	-10000	0	-0.51	4	4
BID	0	0.017	-10000	0	-0.3	1	1
MAP3K1	-0.005	0.079	-10000	0	-0.26	7	7
MAP3K7	0.008	0.004	-10000	0	-10000	0	0
RB1	0.001	0.016	-10000	0	-10000	0	0
CFLAR	0.011	0.004	-10000	0	-10000	0	0
HGF/MET	-0.068	0.15	-10000	0	-0.34	77	77
ARHGDIB	0.001	0.016	-10000	0	-10000	0	0
FADD	0.008	0.004	-10000	0	-10000	0	0
actin filament polymerization	-0.001	0.016	-10000	0	-10000	0	0
NFKB1	-0.046	0.084	-10000	0	-0.26	6	6
MAPK8	-0.053	0.2	-10000	0	-0.42	88	88
DFFA	0.001	0.016	-10000	0	-0.2	1	1
DNA fragmentation during apoptosis	0.001	0.016	-10000	0	-10000	0	0
FAS/FADD/MET	-0.023	0.08	-10000	0	-0.3	30	30
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	0.008	0.038	-10000	0	-0.52	2	2
FAF1	0.009	0.005	-10000	0	-10000	0	0
PARP1	0.001	0.016	-10000	0	-10000	0	0
DFFB	0.001	0.016	-10000	0	-10000	0	0
CHUK	-0.04	0.074	-10000	0	-10000	0	0
FASLG	0.002	0.059	-10000	0	-0.51	5	5
FAS/FADD	-0.006	0.037	-10000	0	-0.37	4	4
HGF	-0.016	0.11	-10000	0	-0.5	20	20
LMNA	0.001	0.015	-10000	0	-10000	0	0
CASP6	0.001	0.016	-10000	0	-10000	0	0
CASP10	0.007	0.027	-10000	0	-0.52	1	1
CASP3	0.001	0.019	0.2	2	-0.23	1	3
PTPN13	-0.049	0.16	-10000	0	-0.5	45	45
CASP8	0	0.024	0.21	2	-0.37	1	3
IL6	-0.24	0.51	-10000	0	-1.2	88	88
MET	-0.025	0.13	-10000	0	-0.51	26	26
ICAD/CAD	0.001	0.015	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 10	-0.007	0.09	-10000	0	-0.36	8	8
activation of caspase activity by cytochrome c	0	0.017	-10000	0	-0.3	1	1
PAK2	0.001	0.016	-10000	0	-10000	0	0
BCL2	0.008	0.038	-10000	0	-0.52	2	2

×

Signaling events mediated by PRL

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
CCNE1	-0.18	0.25	-10000	0	-0.52	142	142
mol:Halofuginone	0.004	0	-10000	0	-10000	0	0
ITGA1	0.009	0.026	-10000	0	-0.5	1	1
CDKN1A	0.016	0.046	-10000	0	-0.61	1	1
PRL-3/alpha Tubulin	-0.001	0.019	-10000	0	-0.37	1	1
mol:Ca2+	-0.061	0.14	-10000	0	-0.38	63	63
AGT	-0.075	0.19	-10000	0	-0.52	63	63
CCNA2	-0.059	0.15	-10000	0	-0.5	14	14
TUBA1B	0.01	0	-10000	0	-10000	0	0
EGR1	-0.008	0.097	-10000	0	-0.35	29	29
CDK2/Cyclin E1	-0.094	0.12	-10000	0	-0.37	18	18
MAPK3	0.017	0.019	-10000	0	-0.37	1	1
PRL-2 /Rab GGTase beta	0	0	-10000	0	-10000	0	0
MAPK1	0.017	0.019	-10000	0	-0.37	1	1
PTP4A1	0.009	0.074	-10000	0	-10000	0	0
PTP4A3	0.008	0.027	-10000	0	-0.52	1	1
PTP4A2	0.01	0	-10000	0	-10000	0	0
ITGB1	0.017	0.019	-10000	0	-0.37	1	1
SRC	0.01	0	-10000	0	-10000	0	0
RAC1	0.017	0.035	-10000	0	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0	0	-10000	0	-10000	0	0
PRL-1/ATF-5	0.013	0.07	-10000	0	-10000	0	0
RABGGTA	0.01	0	-10000	0	-10000	0	0
BCAR1	0	0.021	0.2	1	-0.37	1	2
RHOC	0.017	0.035	-10000	0	-10000	0	0
RHOA	0.017	0.035	-10000	0	-10000	0	0
cell motility	0.02	0.037	-10000	0	-10000	0	0
PRL-1/alpha Tubulin	0.013	0.068	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	-0.002	0.026	-10000	0	-0.36	2	2
ROCK1	0.02	0.038	-10000	0	-10000	0	0
RABGGTB	0.01	0	-10000	0	-10000	0	0
CDK2	0.01	0	-10000	0	-10000	0	0
mitosis	0.009	0.073	-10000	0	-10000	0	0
ATF5	0.008	0.027	-10000	0	-0.52	1	1

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	-0.002	0.026	-10000	0	-0.36	2	2
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	0.019	0.015	-10000	0	-10000	0	0
protein ubiquitination	-0.09	0.12	-10000	0	-0.51	2	2
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	-0.005	0.018	-10000	0	-10000	0	0
FANCF	0.01	0	-10000	0	-10000	0	0
BRCA1	0.008	0.027	-10000	0	-0.52	1	1
CCNE1	-0.18	0.25	-10000	0	-0.52	142	142
CDK2/Cyclin E1	-0.13	0.18	-10000	0	-0.37	142	142
FANCG	0.01	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	-0.003	0.032	-10000	0	-0.36	3	3
FANCE	0.01	0	-10000	0	-10000	0	0
FANCC	0.01	0	-10000	0	-10000	0	0
NBN	0.01	0	-10000	0	-10000	0	0
FANCA	-0.006	0.091	-10000	0	-0.52	12	12
DNA repair	-0.02	0.13	-10000	0	-0.4	10	10
BRCA1/BARD1/ubiquitin	-0.003	0.032	-10000	0	-0.36	3	3
BARD1/DNA-PK	-0.001	0.019	-10000	0	-0.27	1	1
FANCL	0.01	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.002	0.026	0.36	2	-10000	0	2
BRCA1/BARD1/CTIP/M/R/N Complex	0.031	0.015	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1/TopBP1	-0.002	0.026	-10000	0	-0.3	3	3
BRCA1/BARD1/P53	-0.002	0.023	-10000	0	-0.27	3	3
BARD1/CSTF1/BRCA1	-0.002	0.026	-10000	0	-0.3	3	3
BRCA1/BACH1	0.008	0.027	-10000	0	-0.52	1	1
BARD1	0.007	0.037	-10000	0	-0.51	2	2
PCNA	0.007	0.038	-10000	0	-0.52	2	2
BRCA1/BARD1/UbcH5C	-0.002	0.026	-10000	0	-0.3	3	3
BRCA1/BARD1/UbcH7	-0.002	0.026	-10000	0	-0.3	3	3
BRCA1/BARD1/RAD51/PCNA	-0.057	0.12	-10000	0	-0.28	78	78
BARD1/DNA-PK/P53	-0.001	0.017	-10000	0	-10000	0	0
BRCA1/BARD1/Ubiquitin	-0.003	0.032	-10000	0	-0.36	3	3
BRCA1/BARD1/CTIP	-0.002	0.023	-10000	0	-0.27	2	2
FA complex	0.027	0.026	-10000	0	-10000	0	0
BARD1/EWS	-0.002	0.026	-10000	0	-0.36	2	2
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	0.002	0.023	0.26	3	-10000	0	3
BRCA1/BARD1	-0.091	0.12	-10000	0	-0.51	2	2
CSTF1	0.01	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.002	0.026	-10000	0	-0.37	2	2
CDK2	0.01	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.095	0.21	-10000	0	-0.52	78	78
RAD50	0.01	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.003	0.032	-10000	0	-0.36	3	3
EWSR1	0.01	0	-10000	0	-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	-0.024	0.09	-9999	-0.36	26	26
CRKL	0.008	0.073	-9999	-0.26	17	17
mol:PIP3	-0.016	0.005	-9999	-10000	0	0
AKT1	0.001	0.004	-9999	-10000	0	0
PTK2B	0.007	0.036	-9999	-0.5	2	2
RAPGEF1	0.014	0.07	-9999	-0.33	4	4
RANBP10	0.01	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
HGF/MET/SHIP2	-0.035	0.1	-9999	-0.32	43	43
MAP3K5	0.018	0.075	-9999	-0.37	5	5
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.031	0.091	-9999	-0.32	17	17
AP1	-0.031	0.09	-9999	-0.32	32	32
mol:SU11274	0	0	-9999	-10000	0	0
SHC1	0.01	0	-9999	-10000	0	0
apoptosis	-0.046	0.2	-9999	-0.7	32	32
STAT3 (dimer)	0.009	0.078	-9999	-0.4	4	4
GAB1/CRKL/SHP2/PI3K	-0.017	0.054	-9999	-0.37	2	2
INPP5D	0.006	0.045	-9999	-0.5	3	3
CBL/CRK	0.013	0.07	-9999	-0.33	4	4
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	0.048	-9999	-0.19	26	26
mol:SU5416	0	0	-9999	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.014	0.042	-9999	-0.25	3	3
PAK1	0.007	0.004	-9999	-10000	0	0
HGF/MET/RANBP10	-0.035	0.1	-9999	-0.32	43	43
HRAS	-0.006	0.12	-9999	-0.55	15	15
DOCK1	0.014	0.07	-9999	-0.33	4	4
GAB1	0.002	0.077	-9999	-0.28	17	17
CRK	0.008	0.073	-9999	-0.33	5	5
mol:PHA665752	0	0	-9999	-10000	0	0
mol:GDP	-0.04	0.13	-9999	-0.49	29	29
JUN	0.007	0.036	-9999	-0.5	2	2
EntrezGene:200958	0	0	-9999	-10000	0	0
HGF/MET	-0.022	0.066	-9999	-0.23	29	29
PIK3R1	0.01	0	-9999	-10000	0	0
cell morphogenesis	0.03	0.081	-9999	-0.36	4	4
GRB2/SHC	-0.018	0.055	-9999	-0.23	15	15
FOS	-0.029	0.14	-9999	-0.5	30	30
GLMN	0	0	-9999	-10000	0	0
cell motility	-0.011	0.048	-9999	-0.19	26	26
HGF/MET/MUC20	-0.035	0.1	-9999	-0.32	43	43
cell migration	-0.018	0.054	-9999	-0.23	15	15
GRB2	0.01	0	-9999	-10000	0	0
CBL	0.01	0	-9999	-10000	0	0
MET/RANBP10	-0.024	0.09	-9999	-0.36	26	26
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.003	0.079	-9999	-0.41	4	4
MET/MUC20	-0.024	0.092	-9999	-0.37	26	26
RAP1B	0.019	0.067	-9999	-0.36	2	2
RAP1A	0.019	0.067	-9999	-0.36	2	2
HGF/MET/RANBP9	-0.035	0.1	-9999	-0.32	43	43
RAF1	0.001	0.12	-9999	-0.52	15	15
STAT3	0.009	0.078	-9999	-0.4	4	4
cell proliferation	0.012	0.1	-9999	-0.34	29	29
RPS6KB1	0.002	0.027	-9999	-10000	0	0
MAPK3	-0.014	0.044	-9999	-10000	0	0
MAPK1	-0.014	0.044	-9999	-10000	0	0
RANBP9	0.01	0	-9999	-10000	0	0
MAPK8	0.032	0.064	-9999	-0.3	4	4
SRC	0.01	0.075	-9999	-0.38	4	4
PI3K	-0.018	0.055	-9999	-0.32	3	3
MET/Glomulin	-0.013	0.082	-9999	-0.32	26	26
SOS1	0.01	0	-9999	-10000	0	0
MAP2K1	0.008	0.11	-9999	-0.48	15	15
MET	-0.025	0.13	-9999	-0.51	26	26
MAP4K1	0.013	0.079	-9999	-0.36	7	7
PTK2	0.01	0	-9999	-10000	0	0
MAP2K2	0.008	0.11	-9999	-0.48	15	15
BAD	0.007	0.004	-9999	-10000	0	0
MAP2K4	0.024	0.07	-9999	-0.35	4	4
SHP2/GRB2/SOS1/GAB1	-0.023	0.072	-9999	-0.32	16	16
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	-0.003	0.065	-9999	-0.25	15	15
PLCgamma1/PKC	0	0	-9999	-10000	0	0
HGF	-0.016	0.11	-9999	-0.5	20	20
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	-0.007	0.004	-9999	-10000	0	0
HGF/MET/SHIP	-0.037	0.11	-9999	-0.34	43	43

×

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	0.019	-10000	0	-0.37	1	1
PRKCZ	0.006	0.045	-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	0.038	-10000	0	-0.26	1	1
IRAK/TOLLIP	0.021	0.021	-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	130	130
IL1A	-0.14	0.23	-10000	0	-0.5	114	114
IL1B	-0.008	0.094	-10000	0	-0.36	27	27
IRAK/TRAF6/p62/Atypical PKCs	-0.003	0.026	-10000	0	-10000	0	0
IL1R2	-0.016	0.11	-10000	0	-0.52	19	19
IL1R1	0.007	0.036	-10000	0	-0.5	2	2
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.005	0.046	0.19	8	-0.3	2	10
TOLLIP	0.01	0	-10000	0	-10000	0	0
TICAM2	0.007	0.036	-10000	0	-0.5	2	2
MAP3K3	0.009	0.026	-10000	0	-0.5	1	1
TAK1/TAB1/TAB2	0	0	-10000	0	-10000	0	0
IKK complex/ELKS	0.049	0.019	-10000	0	-10000	0	0
JUN	0.026	0.051	-10000	0	-0.43	1	1
MAP3K7	0.01	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.016	0.06	-10000	0	-0.47	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.076	0.12	-10000	0	-0.35	3	3
PIK3R1	0.01	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.07	0.11	-10000	0	-0.49	1	1
IL1 beta fragment/IL1R1/IL1RAP	-0.019	0.07	-10000	0	-0.27	28	28
NFKB1	0.01	0	-10000	0	-10000	0	0
MAPK8	0.022	0.048	-10000	0	-10000	0	0
IRAK1	0.016	0.024	-10000	0	-0.31	2	2
IL1RN/IL1R1	-0.009	0.056	-10000	0	-0.36	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	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.018	0.052	-10000	0	-0.39	1	1
CHUK	0.01	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.019	0.07	-10000	0	-0.27	28	28
IL1 beta/IL1R2	-0.035	0.1	-10000	0	-0.32	42	42
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.001	0.017	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.014	0.053	-10000	0	-0.42	1	1
IRAK3	-0.003	0.081	-10000	0	-0.5	10	10
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.017	0.062	-10000	0	-0.47	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.044	0.12	-10000	0	-0.46	1	1
IL1 alpha/IL1R1/IL1RAP	-0.086	0.14	-10000	0	-0.3	115	115
RELA	0.01	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.008	0.027	-10000	0	-0.52	1	1
MYD88	0.01	0	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	-0.002	0.022	-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	0.051	-10000	0	-0.39	1	1
CASP1	0.006	0.045	-10000	0	-0.5	3	3
IL1RN/IL1R2	-0.025	0.094	-10000	0	-0.38	26	26
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.018	0.064	-10000	0	-0.49	1	1
TMEM189-UBE2V1	0.003	0.027	-10000	0	-0.52	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.038	0.09	-10000	0	-0.39	2	2
PIK3CA	0.01	0	-10000	0	-10000	0	0
IL1RN	-0.001	0.073	-10000	0	-0.5	8	8
TRAF6/TAK1/TAB1/TAB2	-0.001	0.012	-10000	0	-10000	0	0
MAP2K6	0.016	0.05	-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	-0.007	0.051	-9999	-0.36	8	8
PDGFRB	0.008	0.026	-9999	-0.5	1	1
SPHK1	-0.009	0.02	-9999	-10000	0	0
mol:S1P	-0.011	0.026	-9999	-10000	0	0
S1P1/S1P/Gi	-0.012	0.13	-9999	-0.36	37	37
GNAO1	0.004	0.053	-9999	-0.52	4	4
PDGFB-D/PDGFRB/PLCgamma1	-0.005	0.12	-9999	-0.47	8	8
PLCG1	-0.007	0.13	-9999	-0.34	36	36
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.008	0.026	-9999	-0.5	1	1
GNAI2	0.01	0.003	-9999	-10000	0	0
GNAI3	0.01	0.003	-9999	-10000	0	0
GNAI1	0.007	0.037	-9999	-0.51	2	2
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.007	0.046	-9999	-0.31	8	8
S1P1/S1P	-0.019	0.05	-9999	-0.33	4	4
negative regulation of cAMP metabolic process	-0.012	0.13	-9999	-0.35	37	37
MAPK3	-0.022	0.18	-9999	-0.54	36	36
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	-0.001	0.073	-9999	-0.51	8	8
PLCB2	0.011	0.069	-9999	-0.33	6	6
RAC1	0.01	0	-9999	-10000	0	0
RhoA/GTP	-0.016	0.042	-9999	-0.3	3	3
receptor internalization	-0.018	0.047	-9999	-0.31	4	4
PTGS2	-0.06	0.3	-9999	-0.98	36	36
Rac1/GTP	-0.016	0.042	-9999	-0.3	3	3
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	37	37
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.036	0.15	-9999	-0.5	35	35
MAPK1	-0.022	0.18	-9999	-0.54	36	36
S1P1/S1P/PDGFB-D/PDGFRB	0.012	0.071	-9999	-0.35	4	4
ABCC1	0.01	0.002	-9999	-10000	0	0

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.009	0.039	-9999	-0.32	3	3
NFATC2	0	0.066	-9999	-0.32	14	14
NFATC3	0.011	0.026	-9999	-10000	0	0
CD40LG	-0.034	0.22	-9999	-0.7	17	17
PTGS2	-0.049	0.23	-9999	-0.65	26	26
JUNB	0.007	0.036	-9999	-0.5	2	2
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	0.007	0.037	-9999	-0.5	2	2
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	-0.022	0.13	-9999	-0.52	24	24
CREM	0.01	0	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.047	0.09	-9999	-0.45	9	9
FOS	-0.03	0.14	-9999	-0.51	30	30
IFNG	-0.042	0.22	-9999	-0.62	28	28
AP-1/NFAT1-c-4	-0.1	0.18	-9999	-0.67	19	19
FASLG	-0.026	0.2	-9999	-0.62	17	17
NFAT1-c-4/ICER1	-0.03	0.068	-9999	-0.39	8	8
IL2RA	-0.041	0.22	-9999	-0.6	27	27
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	-0.042	0.23	-9999	-0.68	23	23
JunB/Fra1/NFAT1-c-4	-0.042	0.09	-9999	-0.36	19	19
IL4	-0.028	0.19	-9999	-0.6	15	15
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	0.008	0.027	-9999	-0.52	1	1
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.01	0.001	-9999	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.023	0.089	-9999	-0.37	25	25
AKT1	0.033	0.11	-9999	-0.5	9	9
PTK2B	-0.009	0.13	-9999	-0.59	10	10
VEGFR2 homodimer/Frs2	-0.018	0.14	-9999	-0.72	8	8
CAV1	-0.3	0.25	-9999	-0.5	241	241
CALM1	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.038	0.12	-9999	-0.66	8	8
endothelial cell proliferation	0.039	0.11	-9999	-0.47	9	9
mol:Ca2+	0.007	0.12	-9999	-0.56	9	9
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.034	0.1	-9999	-0.6	8	8
RP11-342D11.1	0.001	0.12	-9999	-0.56	9	9
CDH5	-0.053	0.17	-9999	-0.5	48	48
VEGFA homodimer	0	0	-9999	-10000	0	0
SHC1	0.01	0	-9999	-10000	0	0
SHC2	0.001	0.068	-9999	-0.5	7	7
HRAS/GDP	-0.027	0.086	-9999	-0.48	9	9
SH2D2A	0.008	0.027	-9999	-0.52	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.029	0.091	-9999	-0.47	11	11
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.037	0.11	-9999	-0.63	8	8
VEGFR1 homodimer	0.01	0	-9999	-10000	0	0
SHC/GRB2/SOS1	-0.03	0.095	-9999	-0.53	9	9
GRB10	0.007	0.12	-9999	-0.56	9	9
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	-0.06	0.15	-9999	-0.55	26	26
HRAS	0.01	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	0.007	0.083	-9999	-0.36	9	9
HIF1A	0.01	0	-9999	-10000	0	0
FRS2	0.007	0.038	-9999	-0.52	2	2
oxygen and reactive oxygen species metabolic process	-0.034	0.1	-9999	-0.59	8	8
mol:GTP	0	0	-9999	-10000	0	0
FLT4	-0.003	0.081	-9999	-0.5	10	10
Nck/Pak	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.037	0.11	-9999	-0.63	8	8
mol:GDP	-0.029	0.092	-9999	-0.51	9	9
mol:NADP	0.028	0.1	-9999	-0.41	12	12
eNOS/Hsp90	0.031	0.095	-9999	-0.4	10	10
PIK3R1	0.01	0	-9999	-10000	0	0
mol:IP3	0.007	0.12	-9999	-0.57	9	9
HIF1A/ARNT	0	0	-9999	-10000	0	0
SHB	0.009	0.026	-9999	-0.5	1	1
VEGFA	0.012	0	-9999	-10000	0	0
VEGFC	0.006	0.045	-9999	-0.51	3	3
FAK1/Vinculin	0.008	0.13	-9999	-0.6	10	10
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.049	0.12	-9999	-0.61	9	9
PTPN6	0.01	0	-9999	-10000	0	0
EPAS1	-0.043	0.17	-9999	-0.49	47	47
mol:L-citrulline	0.028	0.1	-9999	-0.41	12	12
ITGAV	0.01	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.035	0.11	-9999	-0.63	8	8
VEGFR2 homodimer/VEGFA homodimer	-0.037	0.11	-9999	-0.61	9	9
VEGFR2/3 heterodimer	-0.024	0.15	-9999	-0.67	12	12
VEGFB	0.01	0	-9999	-10000	0	0
MAPK11	0.008	0.12	-9999	-0.56	10	10
VEGFR2 homodimer	-0.024	0.16	-9999	-0.41	47	47
FLT1	0.01	0	-9999	-10000	0	0
NEDD4	0.01	0.026	-9999	-0.5	1	1
MAPK3	0.012	0.11	-9999	-0.52	9	9
MAPK1	0.012	0.11	-9999	-0.52	9	9
VEGFA145/NRP2	-0.002	0.025	-9999	-0.35	2	2
VEGFR1/2 heterodimer	-0.016	0.13	-9999	-0.69	8	8
KDR	-0.024	0.16	-9999	-0.41	47	47
VEGFA165/NRP1/VEGFR2 homodimer	-0.034	0.11	-9999	-0.59	9	9
SRC	0.01	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.013	0.11	-9999	-0.53	9	9
PI3K	-0.033	0.1	-9999	-0.55	10	10
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.037	0.11	-9999	-0.63	8	8
FES	0.006	0.12	-9999	-0.57	9	9
GAB1	-0.034	0.11	-9999	-0.58	9	9
VEGFR2 homodimer/VEGFA homodimer/Src	-0.037	0.11	-9999	-0.63	8	8
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	-0.1	0.14	-9999	-0.4	37	37
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.037	0.11	-9999	-0.63	8	8
PI3K/GAB1	0.032	0.12	-9999	-0.52	9	9
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.033	0.1	-9999	-0.6	8	8
PRKACA	0.01	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.046	0.13	-9999	-0.61	13	13
HSP90AA1	0.01	0	-9999	-10000	0	0
CDC42	0.007	0.12	-9999	-0.57	9	9
actin cytoskeleton reorganization	-0.037	0.11	-9999	-0.63	8	8
PTK2	0.002	0.14	-9999	-0.65	10	10
EDG1	0.001	0.12	-9999	-0.56	9	9
mol:DAG	0.007	0.12	-9999	-0.57	9	9
CaM/Ca2+	-0.03	0.094	-9999	-0.52	9	9
MAP2K3	0.014	0.11	-9999	-0.54	9	9
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.034	0.11	-9999	-0.58	9	9
PLCG1	0.007	0.12	-9999	-0.57	9	9
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.035	0.11	-9999	-0.58	9	9
IQGAP1	0.01	0	-9999	-10000	0	0
YES1	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.037	0.11	-9999	-0.63	8	8
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.037	0.11	-9999	-0.63	8	8
cell migration	0.015	0.14	-9999	-0.6	9	9
mol:PI-3-4-5-P3	-0.031	0.096	-9999	-0.51	10	10
FYN	0.009	0.026	-9999	-0.5	1	1
VEGFB/NRP1	-0.031	0.097	-9999	-0.53	9	9
mol:NO	0.028	0.1	-9999	-0.41	12	12
PXN	0.01	0	-9999	-10000	0	0
HRAS/GTP	-0.027	0.085	-9999	-0.48	9	9
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.006	0.12	-9999	-0.58	9	9
VHL	0.01	0	-9999	-10000	0	0
ITGB3	-0.024	0.13	-9999	-0.52	25	25
NOS3	0.027	0.11	-9999	-0.46	12	12
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.041	0.12	-9999	-0.62	11	11
RAC1	0.01	0	-9999	-10000	0	0
PRKCA	0.013	0.11	-9999	-0.53	9	9
PRKCB	0.008	0.12	-9999	-0.53	11	11
VCL	0.01	0	-9999	-10000	0	0
VEGFA165/NRP1	0	0.12	-9999	-0.57	9	9
VEGFR1/2 heterodimer/VEGFA homodimer	-0.037	0.11	-9999	-0.63	8	8
VEGFA165/NRP2	-0.002	0.025	-9999	-0.35	2	2
MAPKKK cascade	-0.027	0.084	-9999	-0.49	8	8
NRP2	0.007	0.036	-9999	-0.5	2	2
VEGFC homodimer	0.006	0.045	-9999	-0.51	3	3
NCK1	0.01	0	-9999	-10000	0	0
ROCK1	0.01	0	-9999	-10000	0	0
FAK1/Paxillin	0.008	0.13	-9999	-0.6	10	10
MAP3K13	0.007	0.12	-9999	-0.57	9	9
PDPK1	0.03	0.1	-9999	-0.47	9	9

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.016	0.085	-10000	0	-0.43	3	3
IKBKB	-0.002	0.047	-10000	0	-0.25	2	2
AKT1	-0.03	0.081	-10000	0	-0.26	3	3
IKBKG	0	0.049	-10000	0	-0.25	3	3
CALM1	-0.015	0.082	0.23	1	-0.61	4	5
PIK3CA	0.01	0	-10000	0	-10000	0	0
MAP3K1	-0.036	0.11	-10000	0	-0.57	3	3
MAP3K7	0.01	0	-10000	0	-10000	0	0
mol:Ca2+	-0.022	0.086	0.23	1	-0.66	4	5
DOK1	0.01	0	-10000	0	-10000	0	0
AP-1	-0.006	0.06	-10000	0	-0.26	4	4
LYN	0.01	0	-10000	0	-10000	0	0
BLNK	0.009	0.026	-10000	0	-0.5	1	1
SHC1	0.01	0	-10000	0	-10000	0	0
BCR complex	-0.079	0.16	-10000	0	-0.4	78	78
CD22	-0.05	0.1	-10000	0	-0.54	8	8
CAMK2G	-0.008	0.076	0.22	1	-0.56	4	5
CSNK2A1	0.01	0	-10000	0	-10000	0	0
INPP5D	0.006	0.045	-10000	0	-0.5	3	3
SHC/GRB2/SOS1	-0.048	0.1	-10000	0	-0.44	10	10
GO:0007205	-0.022	0.088	0.23	1	-0.68	4	5
SYK	0.006	0.044	-10000	0	-0.5	3	3
ELK1	-0.015	0.083	0.23	1	-0.63	4	5
NFATC1	-0.056	0.12	-10000	0	-0.41	12	12
B-cell antigen/BCR complex	-0.079	0.16	-10000	0	-0.4	78	78
PAG1/CSK	0	0	-10000	0	-10000	0	0
NFKBIB	0.006	0.019	-10000	0	-10000	0	0
HRAS	-0.014	0.081	0.21	1	-0.56	4	5
NFKBIA	0.007	0.018	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.011	0.016	-10000	0	-10000	0	0
RasGAP/Csk	-0.054	0.12	-10000	0	-0.51	8	8
mol:GDP	-0.022	0.085	0.24	1	-0.66	4	5
PTEN	0.01	0	-10000	0	-10000	0	0
CD79B	-0.002	0.079	-10000	0	-0.52	9	9
NF-kappa-B/RelA/I kappa B alpha	0.011	0.015	-10000	0	-10000	0	0
GRB2	0.01	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.065	0.13	-10000	0	-0.59	4	4
PIK3R1	0.01	0	-10000	0	-10000	0	0
mol:IP3	-0.027	0.087	0.23	1	-0.69	4	5
CSK	0.01	0	-10000	0	-10000	0	0
FOS	-0.026	0.1	0.23	1	-0.41	13	14
CHUK	0	0.049	-10000	0	-0.25	3	3
IBTK	0.01	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.032	0.074	-10000	0	-0.48	5	5
PTPN6	-0.046	0.098	-10000	0	-0.5	8	8
RELA	0.01	0	-10000	0	-10000	0	0
BCL2A1	0.01	0.019	-10000	0	-0.098	5	5
VAV2	-0.11	0.15	-10000	0	-0.37	75	75
ubiquitin-dependent protein catabolic process	0.01	0.018	-10000	0	-10000	0	0
BTK	-0.067	0.25	-10000	0	-1	25	25
CD19	-0.13	0.17	-10000	0	-0.42	75	75
MAP4K1	0.003	0.057	-10000	0	-0.5	5	5
CD72	0.007	0.037	-10000	0	-0.51	2	2
PAG1	0.01	0	-10000	0	-10000	0	0
MAPK14	-0.025	0.1	-10000	0	-0.56	2	2
SH3BP5	0.005	0.051	-10000	0	-0.5	4	4
PIK3AP1	-0.015	0.1	0.21	3	-0.56	8	11
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.013	0.11	-10000	0	-0.81	5	5
RAF1	-0.007	0.077	0.21	1	-0.52	4	5
RasGAP/p62DOK/SHIP	-0.053	0.11	-10000	0	-0.48	9	9
CD79A	-0.094	0.21	-10000	0	-0.52	77	77
re-entry into mitotic cell cycle	-0.006	0.06	-10000	0	-0.26	4	4
RASA1	0.01	0	-10000	0	-10000	0	0
MAPK3	0.006	0.066	-10000	0	-0.42	4	4
MAPK1	0.006	0.066	-10000	0	-0.42	4	4
CD72/SHP1	-0.016	0.1	-10000	0	-0.47	8	8
NFKB1	0.01	0	-10000	0	-10000	0	0
MAPK8	-0.025	0.1	-10000	0	-0.47	3	3
actin cytoskeleton organization	-0.075	0.15	-10000	0	-0.32	75	75
NF-kappa-B/RelA	0.027	0.028	-10000	0	-10000	0	0
Calcineurin	-0.021	0.059	-10000	0	-0.5	4	4
PI3K	-0.098	0.12	-10000	0	-0.42	11	11
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.028	0.087	0.22	3	-0.71	4	7
SOS1	0.01	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.01	0.1	-10000	0	-0.7	5	5
DAPP1	-0.029	0.095	-10000	0	-0.89	3	3
cytokine secretion	-0.052	0.12	-10000	0	-0.38	12	12
mol:DAG	-0.027	0.087	0.23	1	-0.69	4	5
PLCG2	0.006	0.044	-10000	0	-0.5	3	3
MAP2K1	0	0.072	0.2	1	-0.47	4	5
B-cell antigen/BCR complex/FcgammaRIIB	-0.066	0.14	-10000	0	-0.34	78	78
mol:PI-3-4-5-P3	-0.075	0.093	-10000	0	-0.3	11	11
ETS1	-0.001	0.07	0.22	1	-0.5	4	5
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.057	0.12	-10000	0	-0.51	10	10
B-cell antigen/BCR complex/LYN	-0.04	0.091	-10000	0	-0.4	9	9
MALT1	0.01	0	-10000	0	-10000	0	0
TRAF6	0.01	0	-10000	0	-10000	0	0
RAC1	-0.079	0.16	-10000	0	-0.34	75	75
B-cell antigen/BCR complex/LYN/SYK	-0.056	0.11	-10000	0	-0.41	16	16
CARD11	-0.029	0.098	0.23	1	-0.54	6	7
FCGR2B	0.01	0	-10000	0	-10000	0	0
PPP3CA	0.01	0	-10000	0	-10000	0	0
BCL10	0.01	0	-10000	0	-10000	0	0
IKK complex	0.004	0.024	-10000	0	-0.093	1	1
PTPRC	-0.003	0.081	-10000	0	-0.5	10	10
PDPK1	-0.032	0.08	-10000	0	-0.25	3	3
PPP3CB	0.01	0	-10000	0	-10000	0	0
PPP3CC	0.01	0	-10000	0	-10000	0	0
POU2F2	0.012	0.013	-10000	0	-0.096	2	2

×

ErbB2/ErbB3 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.015	0.004	-9999	-10000	0	0
RAS family/GTP	-0.037	0.073	-9999	-0.26	4	4
NFATC4	-0.005	0.085	-9999	-0.32	1	1
ERBB2IP	0.01	0.002	-9999	-10000	0	0
HSP90 (dimer)	0.01	0	-9999	-10000	0	0
mammary gland morphogenesis	-0.045	0.09	-9999	-0.42	1	1
JUN	0.02	0.064	-9999	-0.32	1	1
HRAS	0.01	0.001	-9999	-10000	0	0
DOCK7	-0.014	0.099	-9999	-0.4	1	1
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.05	0.1	-9999	-0.27	16	16
AKT1	0.009	0.003	-9999	-10000	0	0
BAD	0.015	0.002	-9999	-10000	0	0
MAPK10	-0.04	0.072	-9999	-0.27	19	19
mol:GTP	0	0.001	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.022	0.11	-9999	-0.46	1	1
RAF1	0.006	0.092	-9999	-0.28	3	3
ErbB2/ErbB3/neuregulin 2	-0.035	0.091	-9999	-0.27	51	51
STAT3	0.001	0.001	-9999	-10000	0	0
cell migration	-0.002	0.079	-9999	-0.22	18	18
mol:PI-3-4-5-P3	-0.001	0.002	-9999	-10000	0	0
cell proliferation	-0.006	0.17	-9999	-0.52	18	18
FOS	-0.009	0.17	-9999	-0.45	39	39
NRAS	0.01	0.001	-9999	-10000	0	0
mol:Ca2+	-0.045	0.09	-9999	-0.42	1	1
MAPK3	0.001	0.13	-9999	-0.47	9	9
MAPK1	0.001	0.13	-9999	-0.47	9	9
JAK2	-0.015	0.1	-9999	-0.4	1	1
NF2	-0.002	0.004	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.029	0.11	-9999	-0.24	77	77
NRG1	-0.089	0.2	-9999	-0.5	76	76
GRB2/SOS1	0	0	-9999	-10000	0	0
MAPK8	-0.016	0.11	-9999	-0.26	6	6
MAPK9	-0.022	0.044	-9999	-0.2	1	1
ERBB2	-0.002	0.027	-9999	-0.38	2	2
ERBB3	0.005	0.037	-9999	-0.5	2	2
SHC1	0.01	0.002	-9999	-10000	0	0
RAC1	0.01	0	-9999	-10000	0	0
apoptosis	0.001	0.007	-9999	-10000	0	0
STAT3 (dimer)	0.001	0.002	-9999	-10000	0	0
RNF41	0.018	0.009	-9999	-10000	0	0
FRAP1	0.007	0.002	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.031	0.061	-9999	-0.28	1	1
ErbB2/ErbB2/HSP90 (dimer)	-0.002	0.022	-9999	-0.32	2	2
CHRNA1	0	0.14	-9999	-0.46	18	18
myelination	-0.002	0.085	-9999	-0.31	1	1
PPP3CB	-0.013	0.094	-9999	-0.37	1	1
KRAS	0.01	0.001	-9999	-10000	0	0
RAC1-CDC42/GDP	-0.039	0.08	-9999	-0.28	1	1
NRG2	-0.052	0.17	-9999	-0.5	47	47
mol:GDP	-0.028	0.11	-9999	-0.24	77	77
SOS1	0.01	0.001	-9999	-10000	0	0
MAP2K2	0.012	0.091	-9999	-0.31	3	3
SRC	0.01	0	-9999	-10000	0	0
mol:cAMP	-0.001	0.001	-9999	-10000	0	0
PTPN11	-0.015	0.099	-9999	-0.4	1	1
MAP2K1	-0.012	0.14	-9999	-0.42	13	13
heart morphogenesis	-0.045	0.09	-9999	-0.42	1	1
RAS family/GDP	-0.037	0.075	-9999	-0.26	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	3	3
HSP90AA1	0.01	0	-9999	-10000	0	0
activation of caspase activity	-0.009	0.003	-9999	-10000	0	0
nervous system development	-0.045	0.09	-9999	-0.42	1	1
CDC42	0.01	0	-9999	-10000	0	0

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0.031	0.1	0.36	34	-10000	0	34
KIRREL	-0.005	0.081	-10000	0	-0.5	10	10
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.031	0.1	-10000	0	-0.36	34	34
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	-0.022	0.071	-10000	0	-10000	0	0
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.01	0.052	-10000	0	-0.24	9	9
FYN	-0.005	0.069	-10000	0	-0.24	10	10
mol:Ca2+	-0.022	0.071	-10000	0	-0.26	2	2
mol:DAG	-0.022	0.071	-10000	0	-0.26	2	2
NPHS2	-0.001	0.014	-10000	0	-10000	0	0
mol:IP3	-0.022	0.071	-10000	0	-0.26	2	2
regulation of endocytosis	-0.018	0.059	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/Cholesterol	-0.023	0.073	-10000	0	-0.26	34	34
establishment of cell polarity	-0.031	0.1	-10000	0	-0.36	34	34
Nephrin/NEPH1/podocin/NCK1-2	-0.019	0.063	-10000	0	-10000	0	0
Nephrin/NEPH1/beta Arrestin2	-0.019	0.059	-10000	0	-10000	0	0
NPHS1	-0.025	0.12	-10000	0	-0.51	24	24
Nephrin/NEPH1/podocin	-0.02	0.065	-10000	0	-0.25	10	10
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	-0.022	0.071	-10000	0	-0.26	2	2
CD2AP	0.01	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.022	0.071	-10000	0	-0.26	2	2
GRB2	0.01	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.022	0.099	-10000	0	-0.28	27	27
cytoskeleton organization	0.013	0.061	-10000	0	-10000	0	0
Nephrin/NEPH1	-0.022	0.071	-10000	0	-0.25	34	34
Nephrin/NEPH1/ZO-1	-0.024	0.078	-10000	0	-0.28	34	34

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.017	0.079	-10000	0	-0.54	7	7
FYN	0.034	0.12	-10000	0	-0.65	9	9
LAT/GRAP2/SLP76	-0.015	0.1	-10000	0	-0.57	9	9
IKBKB	0.01	0	-10000	0	-10000	0	0
AKT1	0.039	0.09	-10000	0	-0.44	9	9
B2M	0.011	0.003	-10000	0	-10000	0	0
IKBKG	-0.008	0.023	-10000	0	-0.13	4	4
MAP3K8	0.007	0.036	-10000	0	-0.5	2	2
mol:Ca2+	-0.009	0.023	-10000	0	-0.1	8	8
integrin-mediated signaling pathway	-0.002	0.021	-10000	0	-0.3	2	2
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.037	0.13	-10000	0	-0.66	9	9
TRPV6	-0.07	0.18	-10000	0	-0.51	54	54
CD28	0.01	0.002	-10000	0	-10000	0	0
SHC1	0.034	0.12	-10000	0	-0.71	7	7
receptor internalization	0.025	0.12	-10000	0	-0.58	11	11
PRF1	-0.006	0.24	-10000	0	-1.1	17	17
KRAS	0.01	0	-10000	0	-10000	0	0
GRB2	0.01	0	-10000	0	-10000	0	0
COT/AKT1	0.039	0.077	-10000	0	-0.37	9	9
LAT	0.033	0.12	-10000	0	-0.71	7	7
EntrezGene:6955	0.001	0.004	-10000	0	-10000	0	0
CD3D	0.008	0.037	-10000	0	-0.51	2	2
CD3E	0.007	0.046	-10000	0	-0.52	3	3
CD3G	0	0.073	-10000	0	-0.51	8	8
RASGRP2	0.002	0.043	-10000	0	-0.16	24	24
RASGRP1	0.038	0.1	-10000	0	-0.44	11	11
HLA-A	0.011	0.003	-10000	0	-10000	0	0
RASSF5	0.007	0.036	-10000	0	-0.5	2	2
RAP1A/GTP/RAPL	-0.002	0.021	-10000	0	-0.3	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.029	0.036	-10000	0	-0.12	9	9
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.014	0.04	-10000	0	-0.21	7	7
PRKCA	-0.005	0.051	-10000	0	-0.28	7	7
GRAP2	-0.006	0.088	-10000	0	-0.5	12	12
mol:IP3	0.009	0.1	0.21	46	-0.43	8	54
EntrezGene:6957	0.001	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	0.017	0.11	-10000	0	-0.67	7	7
ORAI1	0.04	0.098	0.28	54	-10000	0	54
CSK	0.032	0.12	-10000	0	-0.72	7	7
B7 family/CD28	-0.031	0.13	-10000	0	-0.67	12	12
CHUK	0.01	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	0.027	0.14	-10000	0	-0.78	8	8
PTPN6	0.03	0.12	-10000	0	-0.71	7	7
VAV1	0.031	0.12	-10000	0	-0.64	10	10
Monovalent TCR/CD3	0.01	0.085	-10000	0	-0.36	13	13
CBL	0.01	0	-10000	0	-10000	0	0
LCK	0.032	0.12	-10000	0	-0.7	8	8
PAG1	0.032	0.12	-10000	0	-0.72	7	7
RAP1A	0.01	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	0.026	0.13	-10000	0	-0.76	8	8
CD80	-0.003	0.081	-10000	0	-0.5	10	10
CD86	0.001	0.068	-10000	0	-0.51	7	7
PDK1/CARD11/BCL10/MALT1	-0.017	0.048	-10000	0	-0.26	7	7
HRAS	0.01	0	-10000	0	-10000	0	0
GO:0035030	0.027	0.12	-10000	0	-0.55	12	12
CD8A	0.004	0.059	-10000	0	-0.51	5	5
CD8B	0.002	0.07	-10000	0	-0.52	7	7
PTPRC	-0.003	0.081	-10000	0	-0.5	10	10
PDK1/PKC theta	0.035	0.12	-10000	0	-0.45	15	15
CSK/PAG1	0.036	0.11	-10000	0	-0.68	7	7
SOS1	0.01	0	-10000	0	-10000	0	0
peptide-MHC class I	0.016	0.006	-10000	0	-10000	0	0
GRAP2/SLP76	-0.018	0.12	-10000	0	-0.56	13	13
STIM1	0.02	0.048	-10000	0	-10000	0	0
RAS family/GTP	0.039	0.041	-10000	0	-0.16	6	6
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	0.024	0.14	-10000	0	-0.63	11	11
mol:DAG	-0.005	0.073	-10000	0	-0.37	9	9
RAP1A/GDP	0.014	0.016	-10000	0	-0.063	1	1
PLCG1	0.01	0	-10000	0	-10000	0	0
CD247	0.004	0.058	-10000	0	-0.51	5	5
cytotoxic T cell degranulation	-0.003	0.22	-10000	0	-1	17	17
RAP1A/GTP	-0.004	0.014	-10000	0	-0.065	5	5
mol:PI-3-4-5-P3	0.039	0.11	-10000	0	-0.53	9	9
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.006	0.12	0.23	46	-0.55	9	55
NRAS	0.01	0	-10000	0	-10000	0	0
ZAP70	0.002	0.063	-10000	0	-0.5	6	6
GRB2/SOS1	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.014	0.1	-10000	0	-0.55	9	9
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	-0.47	9	9
CARD11	-0.018	0.12	-10000	0	-0.52	21	21
PRKCB	-0.007	0.063	-10000	0	-0.3	13	13
PRKCE	-0.005	0.052	-10000	0	-0.28	7	7
PRKCQ	0.028	0.13	-10000	0	-0.5	17	17
LCP2	0.007	0.036	-10000	0	-0.5	2	2
BCL10	0.01	0	-10000	0	-10000	0	0
regulation of survival gene product expression	0.039	0.078	-10000	0	-0.37	9	9
IKK complex	0.038	0.033	-10000	0	-0.11	8	8
RAS family/GDP	-0.001	0.005	-10000	0	-10000	0	0
MAP3K14	0.04	0.06	-10000	0	-0.28	8	8
PDPK1	0.042	0.086	-10000	0	-0.43	8	8
TCR/CD3/MHC I/CD8/Fyn	0.024	0.13	-10000	0	-0.82	7	7

×

IL2 signaling events mediated by STAT5

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
GAB2	0.005	0.051	-9999	-0.5	4	4
ELF1	-0.001	0.061	-9999	-0.33	1	1
CCNA2	-0.13	0.23	-9999	-0.52	103	103
PIK3CA	0.01	0	-9999	-10000	0	0
JAK3	0.01	0	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
JAK1	0.01	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.051	0.049	-9999	-0.51	1	1
SHC1	0.01	0	-9999	-10000	0	0
SP1	0.008	0.051	-9999	-0.33	9	9
IL2RA	-0.008	0.12	-9999	-0.4	31	31
IL2RB	0.008	0.036	-9999	-0.5	2	2
SOS1	0.01	0	-9999	-10000	0	0
IL2RG	0.005	0.051	-9999	-0.5	4	4
G1/S transition of mitotic cell cycle	-0.022	0.13	-9999	-0.68	10	10
PTPN11	0.01	0	-9999	-10000	0	0
CCND2	0.007	0.11	-9999	-0.73	9	9
LCK	0.008	0.037	-9999	-0.51	2	2
GRB2	0.01	0	-9999	-10000	0	0
IL2	0.006	0.005	-9999	-10000	0	0
CDK6	0.007	0.037	-9999	-0.51	2	2
CCND3	0.055	0.044	-9999	-10000	0	0

×

Arf6 trafficking events

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
SLC2A4	0.003	0.058	-9999	-0.5	5	5
CLTC	0.006	0.052	-9999	-10000	0	0
calcium ion-dependent exocytosis	0.02	0.003	-9999	-10000	0	0
Dynamin 2/GTP	-0.033	0.09	-9999	-0.28	47	47
EXOC4	0.01	0	-9999	-10000	0	0
CD59	0.011	0.034	-9999	-10000	0	0
CPE	0.002	0.065	-9999	-0.31	16	16
CTNNB1	0.01	0	-9999	-10000	0	0
membrane fusion	0	0	-9999	-10000	0	0
CTNND1	-0.008	0.09	-9999	-0.25	47	47
DNM2	0.01	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.017	0.024	-9999	-10000	0	0
TSHR	-0.02	0.1	-9999	-0.31	41	41
INS	0.006	0.009	-9999	-10000	0	0
BIN1	0.01	0	-9999	-10000	0	0
mol:Choline	0	0	-9999	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-9999	-10000	0	0
mol:GDP	-0.024	0.11	-9999	-0.31	47	47
membrane depolarization	0	0	-9999	-10000	0	0
ARF6	0.01	0	-9999	-10000	0	0
mol:Ca2+	-0.033	0.089	-9999	-0.28	47	47
JUP	0.01	0.035	-9999	-10000	0	0
ASAP2/amphiphysin II	0	0	-9999	-10000	0	0
ARF6/GTP	0	0	-9999	-10000	0	0
CDH1	0.009	0.037	-9999	-10000	0	0
clathrin-independent pinocytosis	0	0	-9999	-10000	0	0
MAPK8IP3	0.01	0	-9999	-10000	0	0
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	0.023	0.062	-9999	-10000	0	0
positive regulation of phagocytosis	0.015	0	-9999	-10000	0	0
ARF6/GTP/JIP3	0	0	-9999	-10000	0	0
ACAP1	0.02	0.009	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CHRM2	-0.032	0.093	-9999	-0.34	11	11
clathrin heavy chain/ACAP1	0.012	0.049	-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	-0.008	0.09	-9999	-0.25	47	47
NME1	-0.024	0.11	-9999	-0.31	47	47
clathrin coat assembly	0.006	0.052	-9999	-10000	0	0
IL2RA	0	0.05	-9999	-0.22	3	3
VAMP3	0.015	0	-9999	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.016	0.045	-9999	-0.34	2	2
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	0.017	0.025	-9999	-10000	0	0
SDC1	0.011	0.034	-9999	-10000	0	0
ARF6/GDP	-0.025	0.11	-9999	-0.31	47	47
EXOC7	0.01	0	-9999	-10000	0	0
E-cadherin/beta catenin	-0.024	0.063	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
endocytosis	0	0	-9999	-10000	0	0
SCAMP2	0.01	0	-9999	-10000	0	0
ADRB2	-0.084	0.14	-9999	-0.37	30	30
EXOC3	0.01	0	-9999	-10000	0	0
ASAP2	0.01	0	-9999	-10000	0	0
Dynamin 2/GDP	-0.016	0.096	-9999	-0.28	47	47
KLC1	0.01	0	-9999	-10000	0	0
AVPR2	-0.047	0.12	-9999	-0.25	93	93
RALA	0.01	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.021	0.057	-9999	-10000	0	0

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.043	0.11	-10000	0	-0.33	51	51
cell-cell adhesion	0.05	0.095	0.41	8	-10000	0	8
Ephrin B/EPHB2/RasGAP	-0.035	0.086	-10000	0	-10000	0	0
ITSN1	0.01	0	-10000	0	-10000	0	0
PIK3CA	0.01	0	-10000	0	-10000	0	0
SHC1	0.01	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.009	0.053	-10000	0	-0.31	12	12
Ephrin B1/EPHB1	-0.038	0.1	-10000	0	-0.31	48	48
HRAS/GDP	-0.034	0.074	-10000	0	-0.29	7	7
Ephrin B/EPHB1/GRB7	-0.037	0.092	-10000	0	-0.51	2	2
Endophilin/SYNJ1	-0.006	0.091	-10000	0	-10000	0	0
KRAS	0.01	0	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.034	0.085	-10000	0	-10000	0	0
endothelial cell migration	-0.002	0.021	-10000	0	-10000	0	0
GRB2	0.01	0	-10000	0	-10000	0	0
GRB7	0.003	0.058	-10000	0	-0.51	5	5
PAK1	-0.003	0.095	-10000	0	-0.46	1	1
HRAS	0.01	0	-10000	0	-10000	0	0
RRAS	-0.008	0.097	-10000	0	-0.48	2	2
DNM1	0.003	0.059	-10000	0	-0.52	5	5
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.006	0.091	-10000	0	-10000	0	0
lamellipodium assembly	-0.05	0.095	-10000	0	-0.41	8	8
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.01	0.057	-10000	0	-10000	0	0
PIK3R1	0.01	0	-10000	0	-10000	0	0
EPHB2	-0.053	0.17	-10000	0	-0.52	47	47
EPHB3	-0.004	0.083	-10000	0	-0.52	10	10
EPHB1	-0.052	0.17	-10000	0	-0.52	46	46
EPHB4	0.01	0	-10000	0	-10000	0	0
mol:GDP	-0.029	0.073	-10000	0	-0.29	3	3
Ephrin B/EPHB2	-0.035	0.088	-10000	0	-10000	0	0
Ephrin B/EPHB3	-0.011	0.052	-10000	0	-0.25	12	12
JNK cascade	-0.035	0.13	-10000	0	-0.5	8	8
Ephrin B/EPHB1	-0.035	0.087	-10000	0	-10000	0	0
RAP1/GDP	-0.024	0.063	-10000	0	-10000	0	0
EFNB2	0.006	0.045	-10000	0	-0.5	3	3
EFNB3	0.006	0.046	-10000	0	-0.51	3	3
EFNB1	0.007	0.036	-10000	0	-0.5	2	2
Ephrin B2/EPHB1-2	-0.067	0.13	-10000	0	-0.3	88	88
RAP1B	0.01	0	-10000	0	-10000	0	0
RAP1A	0.01	0	-10000	0	-10000	0	0
CDC42/GTP	-0.048	0.092	-10000	0	-0.4	8	8
Rap1/GTP	-0.049	0.094	-10000	0	-0.42	8	8
axon guidance	-0.042	0.11	-10000	0	-0.33	51	51
MAPK3	0.022	0.051	-10000	0	-10000	0	0
MAPK1	0.022	0.051	-10000	0	-10000	0	0
Rac1/GDP	0.004	0.08	-10000	0	-10000	0	0
actin cytoskeleton reorganization	-0.04	0.076	-10000	0	-0.34	8	8
CDC42/GDP	0.004	0.08	-10000	0	-10000	0	0
PI3K	-0.002	0.021	-10000	0	-10000	0	0
EFNA5	0.001	0.069	-10000	0	-0.51	7	7
Ephrin B2/EPHB4	-0.002	0.026	-10000	0	-0.3	3	3
Ephrin B/EPHB2/Intersectin/N-WASP	0.007	0.058	-10000	0	-10000	0	0
CDC42	0.01	0	-10000	0	-10000	0	0
RAS family/GTP	-0.048	0.092	-10000	0	-0.4	8	8
PTK2	0.015	0.029	-10000	0	-10000	0	0
MAP4K4	-0.035	0.13	-10000	0	-0.51	8	8
SRC	0.01	0	-10000	0	-10000	0	0
KALRN	0.006	0.045	-10000	0	-0.5	3	3
Intersectin/N-WASP	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.009	0.092	-10000	0	-0.34	1	1
MAP2K1	0.016	0.053	-10000	0	-10000	0	0
WASL	0.01	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.065	0.13	-10000	0	-0.55	8	8
cell migration	0.022	0.055	-10000	0	-10000	0	0
NRAS	0.01	0	-10000	0	-10000	0	0
SYNJ1	-0.007	0.092	-10000	0	-10000	0	0
PXN	0.01	0	-10000	0	-10000	0	0
TF	-0.066	0.14	-10000	0	-0.47	15	15
HRAS/GTP	-0.054	0.1	-10000	0	-0.44	8	8
Ephrin B1/EPHB1-2	-0.067	0.13	-10000	0	-0.3	87	87
cell adhesion mediated by integrin	0	0.045	0.26	8	-10000	0	8
RAC1	0.01	0	-10000	0	-10000	0	0
mol:GTP	-0.058	0.11	-10000	0	-0.47	8	8
RAC1-CDC42/GTP	-0.054	0.1	-10000	0	-0.43	10	10
RASA1	0.01	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.024	0.063	-10000	0	-10000	0	0
ruffle organization	-0.011	0.11	-10000	0	-0.42	8	8
NCK1	0.01	0	-10000	0	-10000	0	0
receptor internalization	-0.003	0.091	-10000	0	-10000	0	0
Ephrin B/EPHB2/KALRN	-0.036	0.089	-10000	0	-0.49	1	1
ROCK1	0.011	0.051	-10000	0	-0.27	12	12
RAS family/GDP	-0.037	0.071	-10000	0	-0.32	7	7
Rac1/GTP	-0.052	0.099	-10000	0	-0.44	8	8
Ephrin B/EPHB1/Src/Paxillin	0.007	0.058	-10000	0	-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	0.015	-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	-0.009	0.098	-9999	-0.52	14	14
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.01	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.003	0.045	-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	0.026	-9999	-0.5	1	1
FYN	0.009	0.026	-9999	-0.5	1	1
MAP3K12	0.01	0	-9999	-10000	0	0
FGR	-0.033	0.14	-9999	-0.5	33	33
p38 alpha/TAB1	-0.015	0.049	-9999	-0.32	5	5
PRKG1	-0.04	0.15	-9999	-0.5	38	38
DUSP8	-0.001	0.072	-9999	-0.5	8	8
PGK/cGMP/p38 alpha	-0.033	0.091	-9999	-0.37	19	19
apoptosis	-0.015	0.047	-9999	-0.33	4	4
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0.01	0	-9999	-10000	0	0
DUSP1	-0.037	0.15	-9999	-0.5	36	36
PAK1	0.01	0	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.001	0.013	-9999	-10000	0	0
TRAF6	0.01	0	-9999	-10000	0	0
RAC1	0.01	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0.01	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.01	0.094	-9999	-0.37	15	15
BLK	-0.06	0.18	-9999	-0.52	52	52
HCK	-0.011	0.1	-9999	-0.5	16	16
MAP2K3	0.01	0	-9999	-10000	0	0
DUSP16	0.01	0	-9999	-10000	0	0
DUSP10	0.009	0.026	-9999	-0.5	1	1
TRAF6/MEKK3	-0.001	0.014	-9999	-0.27	1	1
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.018	0.066	-9999	-0.37	4	4
positive regulation of innate immune response	0.015	0.098	-9999	-0.38	14	14
LCK	0.007	0.037	-9999	-0.51	2	2
p38alpha-beta/MKP7	0.02	0.094	-9999	-0.47	6	6
p38alpha-beta/MKP5	0.019	0.096	-9999	-0.47	7	7
PGK/cGMP	-0.035	0.11	-9999	-0.36	38	38
PAK2	0.01	0	-9999	-10000	0	0
p38alpha-beta/MKP1	0	0.12	-9999	-0.51	10	10
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	-0.066	0.18	-9999	-0.52	56	56

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.016	0.061	-10000	0	-10000	0	0
ER alpha/Gai/GDP/Gbeta gamma	0.002	0.094	-10000	0	-0.37	12	12
AKT1	0.005	0.12	-10000	0	-0.71	11	11
PIK3CA	0.01	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	0.002	0.12	-10000	0	-0.72	11	11
mol:Ca2+	0.012	0.095	-10000	0	-0.43	13	13
IGF1R	0.009	0.026	-10000	0	-0.5	1	1
E2/ER alpha (dimer)/Striatin	-0.018	0.072	-10000	0	-0.31	23	23
SHC1	0.01	0	-10000	0	-10000	0	0
apoptosis	-0.006	0.12	0.68	11	-10000	0	11
RhoA/GTP	-0.012	0.05	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.027	0.077	-10000	0	-0.38	13	13
regulation of stress fiber formation	-0.029	0.052	0.36	1	-10000	0	1
E2/ERA-ERB (dimer)	-0.019	0.073	-10000	0	-0.31	24	24
KRAS	0.01	0	-10000	0	-10000	0	0
G13/GTP	-0.016	0.065	-10000	0	-0.28	23	23
pseudopodium formation	0.029	0.052	-10000	0	-0.36	1	1
E2/ER alpha (dimer)/PELP1	-0.018	0.072	-10000	0	-0.31	23	23
GRB2	0.01	0	-10000	0	-10000	0	0
GNG2	0.009	0.026	-10000	0	-0.5	1	1
GNAO1	0.005	0.052	-10000	0	-0.51	4	4
HRAS	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.011	0.093	-10000	0	-0.43	12	12
E2/ER beta (dimer)	-0.001	0.019	-10000	0	-0.38	1	1
mol:GDP	-0.015	0.064	-10000	0	-0.35	11	11
mol:NADP	0.011	0.093	-10000	0	-0.43	12	12
PIK3R1	0.01	0	-10000	0	-10000	0	0
mol:IP3	0.012	0.099	-10000	0	-0.45	13	13
IGF-1R heterotetramer	0.009	0.026	-10000	0	-0.5	1	1
PLCB1	0.011	0.087	-10000	0	-0.44	12	12
PLCB2	0.006	0.1	-10000	0	-0.47	13	13
IGF1	0.002	0.063	-10000	0	-0.5	6	6
mol:L-citrulline	0.011	0.093	-10000	0	-0.43	12	12
RHOA	0.01	0	-10000	0	-10000	0	0
Gai/GDP	-0.023	0.079	-10000	0	-0.66	3	3
JNK cascade	-0.001	0.019	-10000	0	-0.38	1	1
BCAR1	0.009	0.026	-10000	0	-0.5	1	1
ESR2	0.008	0.027	-10000	0	-0.52	1	1
GNAQ	0.009	0.026	-10000	0	-0.5	1	1
ESR1	-0.021	0.12	-10000	0	-0.51	23	23
Gq family/GDP/Gbeta gamma	0.024	0.054	-10000	0	-0.46	2	2
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.018	0.05	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.027	0.076	-10000	0	-0.38	12	12
GNAZ	-0.036	0.15	-10000	0	-0.5	35	35
E2/ER alpha (dimer)	-0.022	0.087	-10000	0	-0.37	23	23
STRN	0.01	0	-10000	0	-10000	0	0
GNAL	-0.002	0.078	-10000	0	-0.51	9	9
PELP1	0.01	0	-10000	0	-10000	0	0
MAPK11	0.012	0.032	-10000	0	-0.3	4	4
GNAI2	0.01	0	-10000	0	-10000	0	0
GNAI3	0.01	0	-10000	0	-10000	0	0
GNAI1	0.007	0.036	-10000	0	-0.5	2	2
HBEGF	-0.027	0.11	-10000	0	-0.46	7	7
cAMP biosynthetic process	-0.02	0.071	-10000	0	-0.26	31	31
SRC	0.008	0.09	-10000	0	-0.35	12	12
PI3K	0	0	-10000	0	-10000	0	0
GNB1	0.01	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.014	0.056	-10000	0	-0.3	11	11
SOS1	0.01	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.024	0.07	-10000	0	-0.43	5	5
Gs family/GTP	-0.02	0.072	-10000	0	-0.26	31	31
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0	0	-10000	0	-10000	0	0
vasodilation	0.011	0.09	-10000	0	-0.41	12	12
mol:DAG	0.012	0.099	-10000	0	-0.45	13	13
Gs family/GDP/Gbeta gamma	-0.017	0.063	-10000	0	-0.32	11	11
MSN	0.03	0.055	-10000	0	-0.39	1	1
Gq family/GTP	-0.019	0.085	-10000	0	-0.47	12	12
mol:PI-3-4-5-P3	0.003	0.12	-10000	0	-0.7	11	11
NRAS	0.01	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.011	0.09	0.41	12	-10000	0	12
GRB2/SOS1	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.014	0.059	-10000	0	-0.33	11	11
NOS3	0.01	0.097	-10000	0	-0.45	12	12
GNA11	0.009	0.026	-10000	0	-0.5	1	1
MAPKKK cascade	0.019	0.1	-10000	0	-0.52	11	11
E2/ER alpha (dimer)/PELP1/Src	-0.028	0.08	-10000	0	-0.4	12	12
ruffle organization	0.029	0.052	-10000	0	-0.36	1	1
ROCK2	0.025	0.055	-10000	0	-10000	0	0
GNA14	-0.006	0.088	-10000	0	-0.5	12	12
GNA15	0.01	0	-10000	0	-10000	0	0
GNA13	0.01	0	-10000	0	-10000	0	0
MMP9	-0.03	0.13	-10000	0	-0.47	9	9
MMP2	0.014	0.086	-10000	0	-0.54	2	2

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	0.005	0.052	-9999	-0.51	4	4
CDC42/GTP	-0.03	0.072	-9999	-0.41	3	3
PLCG1	-0.003	0.086	-9999	-0.42	3	3
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	-0.029	0.071	-9999	-0.4	3	3
S1PR5	-0.024	0.13	-9999	-0.5	26	26
S1PR4	-0.021	0.12	-9999	-0.5	24	24
MAPK3	-0.003	0.086	-9999	-0.42	3	3
MAPK1	-0.003	0.086	-9999	-0.42	3	3
S1P/S1P5/Gi	-0.012	0.096	-9999	-0.46	5	5
GNAI1	0.007	0.036	-9999	-0.5	2	2
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.02	0.075	-9999	-0.3	26	26
RHOA	0.009	0.064	-9999	-10000	0	0
S1P/S1P4/Gi	-0.01	0.091	-9999	-0.25	27	27
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.036	0.15	-9999	-0.5	35	35
S1P/S1P4/G12/G13	-0.016	0.063	-9999	-0.26	24	24
GNA12	0.01	0	-9999	-10000	0	0
GNA13	0.01	0	-9999	-10000	0	0
CDC42	0.01	0	-9999	-10000	0	0

×

Regulation of nuclear SMAD2/3 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
EP300	0.013	0.007	-10000	0	-10000	0	0
HSPA8	0.008	0.004	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.015	0.082	0.2	1	-0.32	22	23
AKT1	0.007	0.019	-10000	0	-10000	0	0
GSC	-0.026	0.11	-10000	0	-10000	0	0
NKX2-5	-0.034	0.14	-10000	0	-0.52	29	29
muscle cell differentiation	0.021	0.057	0.33	3	-10000	0	3
SMAD2-3/SMAD4/SP1	0.043	0.055	-10000	0	-10000	0	0
SMAD4	0.018	0.023	-10000	0	-10000	0	0
CBFB	0.01	0	-10000	0	-10000	0	0
SAP18	0.009	0.001	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.012	0.078	-10000	0	-0.29	27	27
SMAD3/SMAD4/VDR	0.01	0.033	-10000	0	-0.32	1	1
MYC	0.01	0.042	-10000	0	-0.5	2	2
CDKN2B	-0.055	0.32	-10000	0	-1.3	26	26
AP1	0.025	0.083	-10000	0	-0.5	2	2
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.043	0.023	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.013	0.091	-10000	0	-0.3	24	24
SP3	0.012	0	-10000	0	-10000	0	0
CREB1	0.01	0	-10000	0	-10000	0	0
FOXH1	-0.055	0.17	-10000	0	-0.52	47	47
SMAD3/SMAD4/GR	0.003	0.023	-10000	0	-10000	0	0
GATA3	0.008	0.048	-10000	0	-0.5	3	3
SKI/SIN3/HDAC complex/NCoR1	0.032	0.015	-10000	0	-10000	0	0
MEF2C/TIF2	-0.045	0.1	-10000	0	-0.46	6	6
endothelial cell migration	-0.004	0.076	1.3	1	-10000	0	1
MAX	0.009	0.004	-10000	0	-10000	0	0
RBBP7	0.009	0.001	-10000	0	-10000	0	0
RBBP4	0.009	0.001	-10000	0	-10000	0	0
RUNX2	0	0.07	-10000	0	-0.52	7	7
RUNX3	0.007	0.036	-10000	0	-0.5	2	2
RUNX1	0.01	0	-10000	0	-10000	0	0
CTBP1	0.01	0	-10000	0	-10000	0	0
NR3C1	0.009	0.004	-10000	0	-10000	0	0
VDR	0.007	0.037	-10000	0	-0.51	2	2
CDKN1A	0.049	0.073	-10000	0	-1.2	1	1
KAT2B	0.011	0.002	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	-0.042	0.1	-10000	0	-0.32	47	47
DCP1A	0.01	0	-10000	0	-10000	0	0
SKI	0.009	0.001	-10000	0	-10000	0	0
SERPINE1	0.003	0.077	-10000	0	-1.3	1	1
SMAD3/SMAD4/ATF2	0.003	0.022	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	-0.009	0.064	-10000	0	-0.3	16	16
SAP30	0.009	0.001	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.012	0.026	-10000	0	-10000	0	0
JUN	0.026	0.082	-10000	0	-0.5	2	2
SMAD3/SMAD4/IRF7	0.001	0.04	-10000	0	-0.43	2	2
TFE3	0.015	0.004	-10000	0	-10000	0	0
COL1A2	-0.01	0.097	-10000	0	-0.42	16	16
mesenchymal cell differentiation	0.003	0.048	0.32	7	-10000	0	7
DLX1	-0.023	0.12	-10000	0	-0.52	22	22
TCF3	0.01	0	-10000	0	-10000	0	0
FOS	-0.024	0.14	-10000	0	-0.5	30	30
SMAD3/SMAD4/Max	0.003	0.023	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.003	0.01	-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	0.043	-10000	0	-0.58	2	2
ESR1	-0.021	0.12	-10000	0	-0.51	23	23
HNF4A	-0.11	0.22	-10000	0	-0.52	86	86
MEF2C	-0.018	0.12	-10000	0	-0.49	5	5
SMAD2-3/SMAD4	-0.005	0.026	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.008	0.018	-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	0.009	0.001	-10000	0	-10000	0	0
HDAC2	0.009	0.001	-10000	0	-10000	0	0
SNIP1	0.008	0.004	-10000	0	-10000	0	0
GCN5L2	0.002	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.005	0.024	-10000	0	-10000	0	0
MSG1/HSC70	-0.024	0.091	-10000	0	-0.36	27	27
SMAD2	0.007	0.021	-10000	0	-10000	0	0
SMAD3	0.019	0.021	-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	0.009	0.001	-10000	0	-10000	0	0
NCOA2	0.007	0.036	-10000	0	-0.5	2	2
NCOA1	0.01	0	-10000	0	-10000	0	0
MYOD/E2A	-0.003	0.032	-10000	0	-0.37	3	3
SMAD2-3/SMAD4/SP1/MIZ-1	0.049	0.053	-10000	0	-10000	0	0
IFNB1	0.031	0.054	-10000	0	-0.58	2	2
SMAD3/SMAD4/MEF2C	-0.004	0.12	-10000	0	-0.48	5	5
CITED1	-0.026	0.13	-10000	0	-0.51	27	27
SMAD2-3/SMAD4/ARC105	-0.003	0.021	-10000	0	-10000	0	0
RBL1	0.01	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.02	0.13	-10000	0	-0.46	26	26
RUNX1-3/PEBPB2	-0.001	0.021	-10000	0	-0.29	2	2
SMAD7	0.049	0.092	-10000	0	-0.83	1	1
MYC/MIZ-1	0.008	0.046	-10000	0	-0.36	2	2
SMAD3/SMAD4	0.025	0.065	0.28	1	-0.38	1	2
IL10	0.033	0.079	-10000	0	-0.49	7	7
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	0.047	-10000	0	-10000	0	0
CDK4	0.008	0.047	-10000	0	-0.52	3	3
PIAS4	0.008	0.004	-10000	0	-10000	0	0
ATF3	-0.011	0.1	-10000	0	-0.5	16	16
SMAD3/SMAD4/SP1	-0.001	0.034	-10000	0	-10000	0	0
FOXG1	-0.052	0.16	-10000	0	-0.52	41	41
FOXO3	0.015	0.025	-10000	0	-10000	0	0
FOXO1	0.015	0.025	-10000	0	-10000	0	0
FOXO4	0.015	0.025	-10000	0	-10000	0	0
heart looping	-0.017	0.12	-10000	0	-0.49	5	5
CEBPB	0.009	0.01	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.016	0.08	-10000	0	-0.33	22	22
MYOD1	-0.003	0.045	-10000	0	-0.52	3	3
SMAD3/SMAD4/HNF4	-0.067	0.13	-10000	0	-0.31	86	86
SMAD3/SMAD4/GATA3	-0.002	0.045	-10000	0	-0.35	1	1
SnoN/SIN3/HDAC complex/NCoR1	0.01	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.004	0.031	-10000	0	-0.32	2	2
SMAD3/SMAD4/SP1-3	0.004	0.031	-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	0.009	0.001	-10000	0	-10000	0	0
SIN3A	0.009	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.049	0.12	-10000	0	-0.37	24	24
ITGB5	0.051	0.035	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.035	0.009	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.036	0.11	-10000	0	-0.31	49	49
AR	-0.055	0.17	-10000	0	-0.5	50	50
negative regulation of cell growth	0.037	0.042	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	-0.001	0.036	-10000	0	-0.34	3	3
E2F5	0.006	0.046	-10000	0	-0.52	3	3
E2F4	0.01	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.03	0.083	-10000	0	-0.32	6	6
SMAD2-3/SMAD4/FOXO1-3a-4	0.025	0.092	-10000	0	-0.31	26	26
TFDP1	0.008	0.027	-10000	0	-0.52	1	1
SMAD3/SMAD4/AP1	0.029	0.084	-10000	0	-0.51	2	2
SMAD3/SMAD4/RUNX2	-0.003	0.048	-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

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.075	0.4	5	-10000	0	5
GNAI2	0.01	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.02	0.075	-10000	0	-0.3	26	26
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.005	0.052	-10000	0	-0.51	4	4
RhoA/GTP	-0.031	0.077	-10000	0	-0.41	5	5
negative regulation of cAMP metabolic process	-0.011	0.095	-10000	0	-0.45	5	5
GNAZ	-0.036	0.15	-10000	0	-0.5	35	35
GNAI3	0.01	0	-10000	0	-10000	0	0
GNA12	0.01	0	-10000	0	-10000	0	0
S1PR5	-0.024	0.13	-10000	0	-0.5	26	26
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.012	0.096	-10000	0	-0.46	5	5
RhoA/GDP	0	0	-10000	0	-10000	0	0
RHOA	0.01	0	-10000	0	-10000	0	0
GNAI1	0.007	0.036	-10000	0	-0.5	2	2

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.009	0.026	-9999	-0.5	1	1
SPHK1	0.006	0.046	-9999	-0.52	3	3
GNAI2	0.01	0	-9999	-10000	0	0
mol:S1P	0.016	0.02	-9999	-0.27	1	1
GNAO1	0.005	0.052	-9999	-0.51	4	4
mol:Sphinganine-1-P	0.014	0.038	-9999	-0.36	4	4
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	-0.001	0.012	-9999	-10000	0	0
GNAI3	0.01	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
S1PR3	0.008	0.027	-9999	-0.52	1	1
S1PR2	0.01	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.002	0.016	-9999	-0.23	1	1
S1PR5	-0.024	0.13	-9999	-0.5	26	26
S1PR4	-0.021	0.12	-9999	-0.5	24	24
GNAI1	0.007	0.036	-9999	-0.5	2	2
S1P/S1P5/G12	-0.018	0.064	-9999	-0.25	26	26
S1P/S1P3/Gq	0.02	0.059	-9999	-0.27	13	13
S1P/S1P4/Gi	-0.005	0.093	-9999	-0.43	4	4
GNAQ	0.009	0.026	-9999	-0.5	1	1
GNAZ	-0.036	0.15	-9999	-0.5	35	35
GNA14	-0.006	0.088	-9999	-0.5	12	12
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	0.009	0.026	-9999	-0.5	1	1
ABCC1	0.01	0	-9999	-10000	0	0

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.009	0.026	-10000	0	-0.5	1	1
ANTXR2	0.009	0.026	-10000	0	-0.5	1	1
negative regulation of myeloid dendritic cell antigen processing and presentation	0	0.005	-10000	0	-0.066	2	2
monocyte activation	-0.013	0.11	-10000	0	-0.45	22	22
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	-0.01	0.05	-10000	0	-0.27	14	14
CYAA	0.011	0.019	-10000	0	-0.25	2	2
MAP2K4	0	0.004	-10000	0	-10000	0	0
IL1B	-0.003	0.067	-10000	0	-0.26	25	25
Channel	-0.001	0.019	-10000	0	-0.27	2	2
NLRP1	-0.002	0.019	-10000	0	-0.26	2	2
CALM1	0.01	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	0	0.005	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0	0.005	0.066	2	-10000	0	2
MAPK3	0	0.004	-10000	0	-10000	0	0
MAPK1	0	0.004	-10000	0	-10000	0	0
PGR	-0.043	0.097	-10000	0	-0.26	65	65
PA/Cellular Receptors	-0.002	0.021	-10000	0	-0.3	2	2
apoptosis	0	0.005	-10000	0	-0.066	2	2
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.011	0.019	-10000	0	-0.26	2	2
macrophage activation	0.016	0.004	-10000	0	-10000	0	0
TNF	-0.02	0.12	-10000	0	-0.5	23	23
VCAM1	-0.013	0.12	-10000	0	-0.46	22	22
platelet activation	0	0.005	-10000	0	-10000	0	0
MAPKKK cascade	-0.01	0.014	-10000	0	-10000	0	0
IL18	0.007	0.048	-10000	0	-0.31	8	8
negative regulation of macrophage activation	0	0.005	-10000	0	-0.066	2	2
LEF	0	0.005	-10000	0	-0.066	2	2
CASP1	-0.002	0.018	-10000	0	-0.23	2	2
mol:cAMP	0	0.005	-10000	0	-10000	0	0
necrosis	0	0.005	-10000	0	-0.066	2	2
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.001	0.018	-10000	0	-0.26	2	2
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	0.024	0	-9999	-10000	0	0
SNTA1	0.006	0.046	-9999	-0.52	3	3
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.02	0.033	-9999	-0.31	4	4
MAPK12	0.013	0.055	-9999	-0.26	15	15
CCND1	0.008	0.057	-9999	-0.44	5	5
p38 gamma/SNTA1	0.016	0.057	-9999	-10000	0	0
MAP2K3	0.01	0	-9999	-10000	0	0
PKN1	0.01	0	-9999	-10000	0	0
G2/M transition checkpoint	0.013	0.055	-9999	-0.26	15	15
MAP2K6	0.007	0.061	-9999	-0.3	15	15
MAPT	0.005	0.074	-9999	-0.29	22	22
MAPK13	0.018	0	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.013	0.017	-9999	-0.32	1	1

×

IL27-mediated signaling events

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
TGFB1	0.01	0.02	-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	-0.005	0.073	0.6	1	-10000	0	1
IL27/IL27R/JAK1	-0.026	0.085	-10000	0	-1.1	1	1
TBX21	0.001	0.14	-10000	0	-0.59	10	10
IL12B	0.004	0.053	-10000	0	-0.52	4	4
IL12A	0.003	0.046	-10000	0	-0.36	6	6
IL6ST	-0.004	0.081	-10000	0	-0.51	10	10
IL27RA/JAK1	0.011	0.062	-10000	0	-1.2	1	1
IL27	-0.005	0.082	-10000	0	-0.51	10	10
TYK2	0.01	0.004	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.061	0.12	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.005	0.073	0.6	1	-10000	0	1
T cell proliferation during immune response	-0.005	0.073	0.6	1	-10000	0	1
MAPKKK cascade	0.005	0.073	-10000	0	-0.6	1	1
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	-0.005	0.084	-10000	0	-0.5	11	11
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.008	0.16	-10000	0	-0.52	15	15
IL27/IL27R/JAK2/TYK2	0.005	0.074	-10000	0	-0.61	1	1
positive regulation of T cell mediated cytotoxicity	0.005	0.073	-10000	0	-0.6	1	1
STAT1 (dimer)	-0.045	0.13	0.48	1	-0.84	3	4
JAK2	0.008	0.026	-10000	0	-0.5	1	1
JAK1	0.01	0.002	-10000	0	-10000	0	0
STAT2 (dimer)	0.01	0.07	-10000	0	-0.58	1	1
T cell proliferation	-0.047	0.13	-10000	0	-0.47	9	9
IL12/IL12R/TYK2/JAK2	0.009	0.074	-10000	0	-0.69	1	1
IL17A	-0.062	0.12	-10000	0	-10000	0	0
mast cell activation	-0.005	0.073	0.6	1	-10000	0	1
IFNG	0.001	0.024	-10000	0	-0.11	4	4
T cell differentiation	-0.003	0.005	-10000	0	-0.02	14	14
STAT3 (dimer)	0.01	0.07	-10000	0	-0.58	1	1
STAT5A (dimer)	0.009	0.075	-10000	0	-0.81	1	1
STAT4 (dimer)	0.01	0.07	-10000	0	-0.58	1	1
STAT4	0.01	0	-10000	0	-10000	0	0
T cell activation	-0.006	0.007	0.12	1	-10000	0	1
IL27R/JAK2/TYK2	-0.014	0.07	-10000	0	-1.1	1	1
GATA3	0.001	0.09	-10000	0	-1.2	2	2
IL18	0.001	0.052	-10000	0	-0.36	8	8
positive regulation of mast cell cytokine production	0.01	0.069	-10000	0	-0.56	1	1
IL27/EBI3	-0.004	0.061	-10000	0	-0.36	11	11
IL27RA	0.001	0.064	-10000	0	-1.2	1	1
IL6	-0.1	0.21	-10000	0	-0.5	88	88
STAT5A	0.009	0.026	-10000	0	-0.5	1	1
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	0.003	0.024	0.46	1	-10000	0	1
IL1B	-0.014	0.089	-10000	0	-0.36	24	24
EBI3	0.008	0.027	-10000	0	-0.51	1	1
TNF	-0.013	0.087	-10000	0	-0.36	23	23

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.056	0.18	-9999	-0.76	5	5
RAD9A	0.01	0	-9999	-10000	0	0
AP1	-0.029	0.098	-9999	-0.36	32	32
IFNAR2	0.008	0.005	-9999	-10000	0	0
AKT1	0.001	0.047	-9999	-0.22	7	7
ER alpha/Oestrogen	-0.022	0.087	-9999	-0.37	23	23
NFX1/SIN3/HDAC complex	0.029	0.018	-9999	-10000	0	0
EGF	-0.097	0.21	-9999	-0.52	78	78
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	-0.079	0.14	-9999	-0.71	5	5
SAP18	0.008	0.004	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	-0.032	0.14	-9999	-0.51	30	30
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	-0.074	0.12	-9999	-0.64	5	5
Mad/Max	0	0	-9999	-10000	0	0
TERT	-0.057	0.18	-9999	-0.79	5	5
CCND1	-0.051	0.2	-9999	-1.2	5	5
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	0.023	0.028	-9999	-10000	0	0
CDKN1B	-0.004	0.088	-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	0.008	0.005	-9999	-10000	0	0
JUN	0.006	0.037	-9999	-0.5	2	2
E6	-0.001	0.003	-9999	-10000	0	0
HPV-16 E6/E6AP	0.006	0.004	-9999	-10000	0	0
FOS	-0.031	0.14	-9999	-0.5	30	30
IFN-gamma/IRF1	-0.03	0.099	-9999	-0.36	33	33
PARP2	0.01	0	-9999	-10000	0	0
BLM	-0.047	0.16	-9999	-0.52	42	42
Telomerase	-0.018	0.056	-9999	-10000	0	0
IRF1	0.011	0.007	-9999	-10000	0	0
ESR1	-0.023	0.12	-9999	-0.51	23	23
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.031	0.019	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.032	0.02	-9999	-10000	0	0
HDAC1	0.008	0.004	-9999	-10000	0	0
HDAC2	0.009	0.005	-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	-0.077	0.13	-9999	-0.72	4	4
NR2F2	0.012	0.007	-9999	-10000	0	0
MAPK3	0.012	0.008	-9999	-10000	0	0
MAPK1	0.012	0.008	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.01	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	-0.009	0.094	-9999	-0.52	13	13
mol:Oestrogen	-0.001	0.002	-9999	-10000	0	0
EGF/EGFR	-0.085	0.16	-9999	-0.38	88	88
MYC	0.005	0.037	-9999	-0.51	2	2
IL2	0.004	0.01	-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	0.01	0.002	-9999	-10000	0	0
TRF2/BLM	-0.036	0.1	-9999	-0.34	42	42
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.077	0.14	-9999	-0.71	5	5
SP1/HDAC2	0.013	0.011	-9999	-10000	0	0
PINX1	0.01	0	-9999	-10000	0	0
Telomerase/EST1A	-0.074	0.12	-9999	-0.64	5	5
Smad3/Myc	0.02	0.023	-9999	-0.29	2	2
911 complex	0	0	-9999	-10000	0	0
IFNG	-0.034	0.14	-9999	-0.51	33	33
Telomerase/PinX1	-0.074	0.12	-9999	-0.64	5	5
Telomerase/AKT1/mTOR/p70S6K	0.008	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	-0.074	0.12	-9999	-0.64	5	5
response to DNA damage stimulus	0.003	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0	0	-9999	-10000	0	0
TRF2/WRN	0	0	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.074	0.12	-9999	-0.64	5	5
E2F1	0	0.066	-9999	-0.53	6	6
ZNFX1	0.008	0.004	-9999	-10000	0	0
PIF1	-0.056	0.18	-9999	-0.52	49	49
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 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
CBL/APS/CAP	-0.012	0.05	-9999	-10000	0	0
TC10/GTP	-0.011	0.048	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	-0.001	0.014	-9999	-10000	0	0
HRAS	0.01	0	-9999	-10000	0	0
APS homodimer	0.009	0.026	-9999	-0.5	1	1
GRB14	-0.028	0.14	-9999	-0.52	28	28
FOXO3	-0.004	0.028	-9999	-0.52	1	1
AKT1	0.023	0.063	-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	-0.016	0.11	-9999	-0.5	20	20
CRK	0.01	0	-9999	-10000	0	0
PTPN1	0.028	0	-9999	-10000	0	0
CAV1	-0.15	0.13	-9999	-0.25	241	241
CBL/APS/CAP/Crk-II/C3G	-0.013	0.053	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/NCK2	-0.001	0.014	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.012	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.03	0.011	-9999	-10000	0	0
RPS6KB1	0.029	0.059	-9999	-10000	0	0
PARD6A	0.009	0.026	-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	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.013	0.046	-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	0.012	-9999	-10000	0	0
PRKCI	-0.004	0.014	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.016	0.057	-9999	-10000	0	0
SHC1	0.01	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0	0	-9999	-10000	0	0
PI3K	-0.001	0.012	-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	0.023	0.063	-9999	-10000	0	0
PRKCZ	-0.007	0.041	-9999	-0.45	3	3
SH2B2	0.009	0.026	-9999	-0.5	1	1
SHC/SHIP	0.024	0.026	-9999	-10000	0	0
F2RL2	-0.037	0.15	-9999	-0.52	35	35
TRIP10	0.01	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	0	0	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0	0	-9999	-10000	0	0
RAPGEF1	0.01	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	-0.014	0.058	-9999	-0.26	21	21
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0	0	-9999	-10000	0	0
INPP5D	0.019	0.027	-9999	-10000	0	0
SOS1	0.01	0	-9999	-10000	0	0
SGK1	-0.003	0.04	-9999	-0.79	1	1
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.01	0	-9999	-10000	0	0
IRS1	0.009	0.026	-9999	-0.5	1	1
p62DOK/RasGAP	0	0	-9999	-10000	0	0
INS	0.003	0	-9999	-10000	0	0
mol:PI-3-4-P2	0.019	0.027	-9999	-10000	0	0
GRB2	0.01	0	-9999	-10000	0	0
EIF4EBP1	0.021	0.074	-9999	-0.42	1	1
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	0.012	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1	-0.001	0.014	-9999	-0.28	1	1
Insulin Receptor/Insulin/IRS3	0	0	-9999	-10000	0	0
Par3/Par6	-0.023	0.073	-9999	-0.25	31	31

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.025	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP1	0	0	-9999	-10000	0	0
mol:DAG	0.02	0.058	-9999	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	0	0	-9999	-10000	0	0
CaM/Ca2+	0.024	0.055	-9999	-10000	0	0
HIF1A	0.016	0	-9999	-10000	0	0
GAB1	0.009	0.026	-9999	-0.5	1	1
AKT1	0.038	0.046	-9999	-10000	0	0
PLCG1	0.02	0.059	-9999	-10000	0	0
NOS3	0.038	0.054	-9999	-10000	0	0
CBL	0.01	0	-9999	-10000	0	0
mol:NO	0.037	0.052	-9999	-10000	0	0
FLT1	0.024	0	-9999	-10000	0	0
PGF	-0.012	0.1	-9999	-0.52	16	16
VEGFR1 homodimer/NRP2/VEGFR121	-0.001	0.018	-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	0.062	-9999	-0.38	3	3
mol:Ca2+	0.02	0.058	-9999	-10000	0	0
MAPK3	0.03	0.057	-9999	-0.46	1	1
MAPK1	0.03	0.057	-9999	-0.46	1	1
PIK3R1	0.01	0	-9999	-10000	0	0
PLGF homodimer	-0.012	0.1	-9999	-0.52	16	16
PRKACA	0.01	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.3	0.25	-9999	-0.5	241	241
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	0.035	0.056	-9999	-0.44	1	1
PI3K	-0.01	0.048	-9999	-10000	0	0
PRKCA	0.024	0.06	-9999	-0.49	1	1
PRKCB	0.02	0.072	-9999	-0.49	2	2
VEGFR1 homodimer/PLGF homodimer	0.012	0.064	-9999	-10000	0	0
VEGFA	0.01	0	-9999	-10000	0	0
VEGFB	0.01	0	-9999	-10000	0	0
mol:IP3	0.02	0.058	-9999	-10000	0	0
RASA1	0.032	0	-9999	-10000	0	0
NRP2	0.007	0.036	-9999	-0.5	2	2
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	-0.1	0.13	-9999	-0.4	12	12
PTPN11	0.01	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.01	0.048	-9999	-10000	0	0
mol:L-citrulline	0.037	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	0.046	-9999	-10000	0	0
PDPK1	0.03	0.052	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/SHP2	0	0	-9999	-10000	0	0
mol:NADP	0.037	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	0.022	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	-0.001	0.013	-9999	-10000	0	0
HDAC3	0.01	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.002	0.019	-9999	-0.22	3	3
GATA1/HDAC4	-0.039	0.11	-9999	-0.35	43	43
GATA1/HDAC5	-0.038	0.11	-9999	-0.35	42	42
GATA2/HDAC5	-0.032	0.1	-9999	-0.35	36	36
HDAC5/BCL6/BCoR	0	0	-9999	-10000	0	0
HDAC9	-0.003	0.082	-9999	-0.51	10	10
Glucocorticoid receptor/Hsp90/HDAC6	-0.001	0.015	-9999	-0.3	1	1
HDAC4/ANKRA2	-0.001	0.019	-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	-0.037	0.15	-9999	-0.5	36	36
HDAC4/RFXANK	-0.001	0.019	-9999	-0.37	1	1
BCOR	0.01	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.009	0.026	-9999	-0.5	1	1
HDAC5	0.01	0	-9999	-10000	0	0
GNB1/GNG2	-0.001	0.018	-9999	-0.35	1	1
Histones	0.027	0.031	-9999	-10000	0	0
ADRBK1	0.01	0	-9999	-10000	0	0
HDAC4	0.008	0.027	-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	0.019	-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	0.008	0.027	-9999	-0.52	1	1
HDAC5/RFXANK	0	0	-9999	-10000	0	0
CAMK4	0.003	0.058	-9999	-0.5	5	5
Tubulin/HDAC6	-0.007	0.046	-9999	-0.3	9	9
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	42	42
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	-0.001	0.012	-9999	-0.24	1	1
SRF	0.01	0	-9999	-10000	0	0
HDAC4/YWHAB	-0.001	0.019	-9999	-0.37	1	1
Tubulin	-0.007	0.052	-9999	-0.37	8	8
HDAC4/14-3-3 E	-0.001	0.019	-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	0.015	-9999	-0.3	1	1
HDAC4/SRF	-0.005	0.036	-9999	-0.3	6	6
HDAC4/ER alpha	-0.022	0.087	-9999	-0.36	24	24
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.027	0.031	-9999	-10000	0	0
cell motility	-0.007	0.046	-9999	-0.3	9	9
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	0.008	0.027	-9999	-0.52	1	1
Hsp90/HDAC6	-0.001	0.019	-9999	-0.37	1	1
ESR1	-0.021	0.12	-9999	-0.51	23	23
HDAC6/HDAC11	-0.001	0.019	-9999	-0.37	1	1
Ran/GTP/Exportin 1	-0.001	0.016	-9999	-0.23	2	2
NPC	0	0	-9999	-10000	0	0
MEF2C	0.01	0	-9999	-10000	0	0
RAN	0.007	0.038	-9999	-0.52	2	2
HDAC4/MEF2C	-0.001	0.012	-9999	-10000	0	0
GNG2	0.009	0.026	-9999	-0.5	1	1
NCOR2	0.01	0	-9999	-10000	0	0
TUBB2A	-0.001	0.075	-9999	-0.52	8	8
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	0.01	-9999	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.01	0.001	-9999	-10000	0	0
HDAC2	0.01	0.001	-9999	-10000	0	0
GNB1/GNG2	-0.004	0.034	-9999	-0.3	5	5
forebrain development	-0.016	0.15	-9999	-0.54	17	17
GNAO1	0.004	0.052	-9999	-0.51	4	4
SMO/beta Arrestin2	0.011	0.039	-9999	-0.37	4	4
SMO	0.004	0.053	-9999	-0.52	4	4
ARRB2	0.009	0.004	-9999	-10000	0	0
GLI3/SPOP	0.034	0.038	-9999	-10000	0	0
mol:GTP	0	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	0.005	0.012	-9999	-10000	0	0
GNAI1	0.006	0.037	-9999	-0.51	2	2
XPO1	0.011	0.005	-9999	-10000	0	0
GLI1/Su(fu)	-0.047	0.11	-9999	-0.56	10	10
SAP30	0.01	0.001	-9999	-10000	0	0
mol:GDP	0.004	0.053	-9999	-0.52	4	4
MIM/GLI2A	0.004	0.041	-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	0.014	-9999	-10000	0	0
GLI3	0.03	0.04	-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	0.009	0.026	-9999	-0.5	1	1
Gi family/GTP	-0.001	0.083	-9999	-0.28	17	17
SIN3B	0.01	0.001	-9999	-10000	0	0
SIN3A	0.01	0.001	-9999	-10000	0	0
GLI3/Su(fu)	0.037	0.034	-9999	-10000	0	0
GLI2/Su(fu)	0.04	0.028	-9999	-10000	0	0
FOXA2	-0.17	0.39	-9999	-1	64	64
neural tube patterning	-0.016	0.15	-9999	-0.54	17	17
SPOP	0.01	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.021	0.018	-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	0.004	0.041	-9999	-0.53	1	1
embryonic limb morphogenesis	-0.016	0.15	-9999	-0.54	17	17
SUFU	0.019	0.02	-9999	-10000	0	0
LGALS3	0.01	0	-9999	-10000	0	0
catabolic process	0.054	0.036	-9999	-10000	0	0
GLI3A/CBP	0.003	0.061	-9999	-0.33	12	12
KIF3A	0.01	0	-9999	-10000	0	0
GLI1	-0.016	0.15	-9999	-0.55	17	17
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	0.018	-9999	-10000	0	0
GNAZ	-0.037	0.15	-9999	-0.5	35	35
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	0.013	-9999	-10000	0	0
STK36	0.01	0.005	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.007	0.077	-9999	-0.5	2	2
PTCH1	-0.014	0.18	-9999	-0.88	10	10
MIM/GLI1	-0.045	0.22	-9999	-0.5	68	68
CREBBP	0.003	0.061	-9999	-0.33	12	12
Su(fu)/SIN3/HDAC complex	0.041	0.007	-9999	-10000	0	0

×

Ceramide 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
SPHK2	0.01	0.056	-10000	0	-0.35	9	9
MAP4K4	0.025	0.055	-10000	0	-0.46	1	1
BAG4	0.008	0.027	-10000	0	-0.52	1	1
PKC zeta/ceramide	-0.012	0.034	-10000	0	-0.25	2	2
NFKBIA	0.01	0	-10000	0	-10000	0	0
BIRC3	0.002	0.064	-10000	0	-0.51	6	6
BAX	-0.003	0.016	-10000	0	-10000	0	0
RIPK1	0.01	0	-10000	0	-10000	0	0
AKT1	0.017	0.008	-10000	0	-10000	0	0
BAD	-0.01	0.032	0.14	4	-10000	0	4
SMPD1	0.013	0.044	-10000	0	-0.23	1	1
RB1	-0.01	0.032	-10000	0	-10000	0	0
FADD/Caspase 8	0.032	0.057	-10000	0	-0.45	2	2
MAP2K4	-0.004	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	-0.004	0.03	-10000	0	-10000	0	0
EGF	-0.095	0.21	-10000	0	-0.52	78	78
mol:ceramide	-0.018	0.034	0.14	4	-10000	0	4
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	0.056	-10000	0	-0.35	9	9
ASAH1	0.009	0.026	-10000	0	-0.5	1	1
negative regulation of cell cycle	-0.01	0.031	-10000	0	-10000	0	0
cell proliferation	-0.009	0.025	-10000	0	-10000	0	0
BID	0.016	0.04	-10000	0	-0.3	1	1
MAP3K1	-0.01	0.032	0.14	4	-10000	0	4
EIF2A	0.002	0.029	-10000	0	-10000	0	0
TRADD	0.01	0	-10000	0	-10000	0	0
CRADD	0.008	0.027	-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	-0.011	0.031	-10000	0	-10000	0	0
FADD	0.025	0.055	-10000	0	-0.46	1	1
KSR1	-0.01	0.032	0.14	4	-10000	0	4
MAPK8	-0.002	0.032	-10000	0	-0.2	2	2
PRKRA	-0.01	0.032	0.14	4	-10000	0	4
PDGFA	-0.001	0.072	-10000	0	-0.5	8	8
TRAF2	0.01	0	-10000	0	-10000	0	0
IGF1	0.002	0.063	-10000	0	-0.5	6	6
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.018	0.034	0.14	4	-10000	0	4
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	0.01	0.034	-10000	0	-10000	0	0
PRKCD	0.01	0	-10000	0	-10000	0	0
PRKCZ	0.006	0.045	-10000	0	-0.5	3	3
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.01	0.056	-10000	0	-0.35	9	9
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	0.019	0.058	-10000	0	-0.49	1	1
TNFR1A/BAG4/TNF-alpha	-0.018	0.07	-10000	0	-0.29	24	24
mol:Sphingosine-1-phosphate	0.01	0.056	-10000	0	-0.35	9	9
MAP2K1	0.002	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	-0.005	0.023	-10000	0	-10000	0	0
TNFRSF1A	0.01	0	-10000	0	-10000	0	0
NFKB1	0.01	0	-10000	0	-10000	0	0
TNFR1A/BAG4	-0.001	0.019	-10000	0	-0.37	1	1
EIF2AK2	-0.004	0.03	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.017	0.069	-10000	0	-0.29	23	23
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.025	0.046	-10000	0	-0.42	2	2
MAP2K2	0.002	0.029	-10000	0	-10000	0	0
SMPD3	0.012	0.051	-10000	0	-0.28	2	2
TNF	-0.02	0.12	-10000	0	-0.5	23	23
PKC zeta/PAR4	-0.003	0.031	-10000	0	-0.35	3	3
mol:PHOSPHOCHOLINE	0.023	0.069	0.16	73	-10000	0	73
NF kappa B1/RelA/I kappa B alpha	-0.002	0.021	-10000	0	-10000	0	0
AIFM1	-0.005	0.023	-10000	0	-10000	0	0
BCL2	0.007	0.038	-10000	0	-0.52	2	2

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	-0.017	0.067	-9999	-0.29	22	22
Ran/GTP/Exportin 1/HDAC1	-0.001	0.016	-9999	-0.22	2	2
NF kappa B1 p50/RelA/I kappa B alpha	-0.016	0.063	-9999	-0.27	22	22
SUMO1	0.01	0	-9999	-10000	0	0
ZFPM1	0.008	0.027	-9999	-0.52	1	1
NPC/RanGAP1/SUMO1/Ubc9	0.017	0	-9999	-10000	0	0
FKBP3	0.008	0.027	-9999	-0.52	1	1
Histones	-0.007	0.03	-9999	-10000	0	0
YY1/LSF	0.024	0	-9999	-10000	0	0
SMG5	0.01	0	-9999	-10000	0	0
RAN	0.007	0.038	-9999	-0.52	2	2
I kappa B alpha/HDAC3	-0.013	0.054	-9999	-10000	0	0
I kappa B alpha/HDAC1	-0.009	0.037	-9999	-10000	0	0
SAP18	0.01	0	-9999	-10000	0	0
RELA	0.016	0.058	-9999	-0.22	22	22
HDAC1/Smad7	-0.001	0.015	-9999	-0.29	1	1
RANGAP1	0.01	0	-9999	-10000	0	0
HDAC3/TR2	-0.009	0.037	-9999	-10000	0	0
NuRD/MBD3 Complex	0.037	0.014	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.019	0.052	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.037	0.15	-9999	-0.5	36	36
GATA1	-0.046	0.16	-9999	-0.5	42	42
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	0.011	0.048	-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	-0.008	0.032	-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	-0.055	0.13	-9999	-0.32	67	67
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)	-0.009	0.037	-9999	-10000	0	0
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.001	0.015	-9999	-0.29	1	1
CREBBP	0.01	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.04	0.014	-9999	-10000	0	0
HDAC1	0.01	0	-9999	-10000	0	0
HDAC3	0.011	0.048	-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	0.026	-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	0.011	0.048	-9999	-10000	0	0
histone deacetylation	0.038	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	-0.008	0.032	-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	-0.033	0.085	-9999	-0.28	36	36
GATA1/HDAC1	-0.038	0.11	-9999	-0.35	42	42
GATA1/HDAC3	-0.037	0.087	-9999	-0.26	42	42
CHD4	0.01	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.021	0.083	-9999	-0.36	23	23
SIN3/HDAC complex/Mad/Max	0.038	0	-9999	-10000	0	0
NuRD Complex	0.043	0.014	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.007	0.03	-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	0	-9999	-10000	0	0
HDAC complex	0	0	-9999	-10000	0	0
GATA1/Fog1	-0.039	0.11	-9999	-0.36	42	42
FKBP25/HDAC1/HDAC2	-0.001	0.015	-9999	-0.3	1	1
TNF	-0.02	0.12	-9999	-0.5	23	23
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	-0.001	0.016	-9999	-0.23	2	2
NF kappa B/RelA/I kappa B alpha	-0.017	0.067	-9999	-0.29	22	22
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	0.007	0.036	-9999	-0.5	2	2
MBD2	0.01	0	-9999	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.01	0	-10000	0	-10000	0	0
HDAC3	0.01	0	-10000	0	-10000	0	0
VDR	0.007	0.037	-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	0.033	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	0.017	0.028	0.2	1	-0.23	2	3
RAR alpha/9cRA/Cyclin H	-0.006	0.024	-10000	0	-10000	0	0
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.03	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	-0.007	0.026	-10000	0	-10000	0	0
NCOR2	0.01	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	-0.002	0.026	-10000	0	-0.37	2	2
RXRs/RARs/NRIP1/9cRA	-0.008	0.069	-10000	0	-0.55	2	2
NCOA2	0.007	0.036	-10000	0	-0.5	2	2
NCOA3	0.01	0	-10000	0	-10000	0	0
NCOA1	0.01	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.007	0.037	-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	0.01	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	-0.041	0.059	-10000	0	-0.59	2	2
RARA	0.013	0.038	-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	0.029	0.026	-10000	0	-10000	0	0
PRKCA	0.01	0.037	-10000	0	-0.5	2	2
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.022	0.077	-10000	0	-0.59	2	2
RXRG	-0.16	0.18	-10000	0	-0.32	197	197
RXRA	0.019	0.036	-10000	0	-0.22	2	2
RXRB	0.006	0.057	-10000	0	-0.31	2	2
VDR/Vit D3/DNA	-0.002	0.026	-10000	0	-0.37	2	2
RBP1	0.002	0.064	-10000	0	-0.52	6	6
CRBP1/9-cic-RA	-0.006	0.046	-10000	0	-0.37	6	6
RARB	0.009	0.037	-10000	0	-0.5	2	2
PRKCG	-0.027	0.14	-10000	0	-0.52	28	28
MNAT1	0.01	0	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.009	0.068	-10000	0	-0.59	2	2
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.001	0.06	-10000	0	-0.45	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.032	0.028	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.022	0.077	-10000	0	-0.59	2	2
positive regulation of DNA binding	-0.005	0.023	-10000	0	-10000	0	0
NRIP1	-0.02	0.072	-10000	0	-0.54	2	2
RXRs/RARs	-0.029	0.078	-10000	0	-0.59	2	2
RXRs/RXRs/DNA/9cRA	-0.044	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	-0.004	0.015	-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

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	0.023	0.018	-9999	-0.22	2	2
epithelial cell differentiation	-0.001	0.017	-9999	-10000	0	0
CYFIP2	0.002	0.063	-9999	-0.5	6	6
ENAH	0.049	0.031	-9999	-0.29	1	1
EGFR	-0.007	0.093	-9999	-0.51	13	13
EPHA2	0.001	0.068	-9999	-0.5	7	7
MYO6	0.029	0.018	-9999	-10000	0	0
CTNNB1	0.01	0	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.004	0.036	-9999	-0.29	6	6
AQP5	-0.1	0.17	-9999	-0.42	85	85
CTNND1	0.01	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.029	0.018	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.11	0.13	-9999	-0.46	1	1
EGF	-0.095	0.21	-9999	-0.52	78	78
NCKAP1	0.01	0	-9999	-10000	0	0
AQP3	-0.02	0.091	-9999	-0.44	17	17
cortical microtubule organization	-0.001	0.017	-9999	-10000	0	0
GO:0000145	0.028	0.017	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.001	0.017	-9999	-10000	0	0
MLLT4	0.01	0	-9999	-10000	0	0
ARF6/GDP	-0.005	0.032	-9999	-0.4	1	1
ARF6	0.01	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.005	0.036	-9999	-0.26	8	8
mol:Ca2+	0	0	-9999	-10000	0	0
VASP	0.038	0.019	-9999	-10000	0	0
PVRL2	0.01	0	-9999	-10000	0	0
ZYX	0.029	0.018	-9999	-10000	0	0
ARF6/GTP	-0.005	0.033	-9999	-10000	0	0
CDH1	0.007	0.036	-9999	-0.5	2	2
EGFR/EGFR/EGF/EGF	-0.053	0.1	-9999	-0.46	3	3
RhoA/GDP	-0.001	0.016	-9999	-10000	0	0
actin cytoskeleton organization	0.034	0.018	-9999	-10000	0	0
IGF-1R heterotetramer	0.009	0.026	-9999	-0.5	1	1
GIT1	0.01	0	-9999	-10000	0	0
IGF1R	0.009	0.026	-9999	-0.5	1	1
IGF1	0.002	0.063	-9999	-0.5	6	6
DIAPH1	-0.009	0.067	-9999	-0.55	6	6
Wnt receptor signaling pathway	0.001	0.017	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
RhoA/GTP	-0.005	0.032	-9999	-0.4	1	1
CTNNA1	0.01	0	-9999	-10000	0	0
VCL	0.034	0.018	-9999	-10000	0	0
EFNA1	0.009	0.026	-9999	-0.5	1	1
LPP	0.034	0.021	-9999	-10000	0	0
Ephrin A1/EPHA2	-0.005	0.038	-9999	-0.45	1	1
SEC6/SEC8	-0.001	0.013	-9999	-10000	0	0
MGAT3	-0.11	0.13	-9999	-0.47	1	1
HGF/MET	-0.027	0.079	-9999	-0.46	4	4
HGF	-0.016	0.11	-9999	-0.5	20	20
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.023	0.018	-9999	-0.23	2	2
actin cable formation	0.061	0.029	-9999	-10000	0	0
KIAA1543	0.033	0.03	-9999	-0.45	1	1
KIFC3	0.029	0.022	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
EXOC3	0.01	0	-9999	-10000	0	0
ACTN1	0.029	0.018	-9999	-10000	0	0
NCK1/GIT1	0	0	-9999	-10000	0	0
mol:GDP	-0.001	0.017	-9999	-10000	0	0
EXOC4	0.01	0	-9999	-10000	0	0
STX4	0.029	0.018	-9999	-10000	0	0
PIP5K1C	0.029	0.018	-9999	-10000	0	0
LIMA1	0.01	0	-9999	-10000	0	0
ABI1	0.01	0	-9999	-10000	0	0
ROCK1	-0.004	0.028	-9999	-0.34	1	1
adherens junction assembly	0.045	0.043	-9999	-0.53	2	2
IGF-1R heterotetramer/IGF1	-0.005	0.032	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
MET	-0.025	0.13	-9999	-0.51	26	26
PLEKHA7	0.029	0.018	-9999	-10000	0	0
mol:GTP	-0.005	0.036	-9999	-0.26	8	8
establishment of epithelial cell apical/basal polarity	0.049	0.016	-9999	-10000	0	0
cortical actin cytoskeleton stabilization	0.023	0.018	-9999	-0.22	2	2
regulation of cell-cell adhesion	0.034	0.018	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.023	0.018	-9999	-0.23	2	2

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.002	0.022	-9999	-10000	0	0
DAPP1	-0.002	0.11	-9999	-0.51	13	13
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.001	0.16	-9999	-0.64	16	16
mol:DAG	0.024	0.068	-9999	-0.24	15	15
HRAS	0.01	0.001	-9999	-10000	0	0
RAP1A	0.01	0.001	-9999	-10000	0	0
ARF5/GDP	0.02	0.074	-9999	-0.42	8	8
PLCG2	0.006	0.045	-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	0.017	-9999	-10000	0	0
ADAP1	-0.002	0.025	-9999	-0.43	1	1
ARAP3	-0.002	0.018	-9999	-10000	0	0
INPPL1	0.01	0	-9999	-10000	0	0
PREX1	0.002	0.063	-9999	-0.5	6	6
ARHGEF6	-0.008	0.095	-9999	-0.5	14	14
ARHGEF7	0.01	0	-9999	-10000	0	0
ARF1	0.01	0	-9999	-10000	0	0
NRAS	0.01	0.001	-9999	-10000	0	0
FYN	0.009	0.026	-9999	-0.5	1	1
ARF6	0.01	0	-9999	-10000	0	0
FGR	-0.033	0.14	-9999	-0.5	33	33
mol:Ca2+	0.021	0.037	-9999	-10000	0	0
mol:IP4	0	0	-9999	-10000	0	0
TIAM1	0.001	0.068	-9999	-0.5	7	7
ZAP70	0.002	0.063	-9999	-0.5	6	6
mol:IP3	0.025	0.05	-9999	-0.22	5	5
LYN	0.01	0	-9999	-10000	0	0
ARF1/GDP	0.02	0.074	-9999	-0.42	8	8
RhoA/GDP	-0.007	0.037	-9999	-0.36	2	2
PDK1/Src/Hsp90	0	0	-9999	-10000	0	0
BLNK	0.009	0.026	-9999	-0.5	1	1
actin cytoskeleton reorganization	0.039	0.066	-9999	-0.43	5	5
SRC	0.01	0	-9999	-10000	0	0
PLEKHA2	0.021	0.032	-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	-0.001	0.016	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT	0	0.12	-9999	-0.49	14	14
BLK	-0.06	0.18	-9999	-0.52	52	52
PDPK1	0.01	0	-9999	-10000	0	0
CYTH1	-0.001	0.016	-9999	-10000	0	0
HCK	-0.011	0.1	-9999	-0.5	16	16
CYTH3	-0.003	0.023	-9999	-10000	0	0
CYTH2	-0.001	0.016	-9999	-10000	0	0
KRAS	0.01	0.001	-9999	-10000	0	0
GO:0030676	0	0	-9999	-10000	0	0
FOXO3	-0.002	0.029	-9999	-0.57	1	1
SGK1	-0.002	0.032	-9999	-0.62	1	1
INPP5D	0.006	0.045	-9999	-0.5	3	3
mol:GDP	0.015	0.078	-9999	-0.45	8	8
SOS1	0.01	0	-9999	-10000	0	0
SYK	0.006	0.045	-9999	-0.5	3	3
ARF6/GDP	-0.007	0.037	-9999	-0.33	3	3
mol:PI-3-4-5-P3	-0.002	0.017	-9999	-10000	0	0
ARAP3/RAP1A/GTP	-0.002	0.018	-9999	-10000	0	0
VAV1	0.003	0.057	-9999	-0.5	5	5
mol:PI-3-4-P2	0.015	0.032	-9999	-0.35	3	3
RAS family/GTP/PI3K Class I	-0.002	0.018	-9999	-10000	0	0
PLEKHA1	0.021	0.027	-9999	-0.29	3	3
Rac1/GDP	0.02	0.074	-9999	-0.42	8	8
LAT	0.008	0.027	-9999	-0.52	1	1
Rac1/GTP	0.011	0.11	-9999	-0.47	16	16
ITK	-0.006	0.036	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.025	0.093	-9999	-0.35	15	15
LCK	0.007	0.037	-9999	-0.51	2	2
BTK	-0.015	0.06	-9999	-0.43	2	2

×

p38 MAPK signaling pathway

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
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	0.022	0.026	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.026	0.03	-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	0.005	0.052	-10000	0	-0.51	4	4
TXN	0.006	0.014	-10000	0	-0.2	2	2
CALM1	0.01	0	-10000	0	-10000	0	0
GADD45A	0.007	0.037	-10000	0	-0.51	2	2
GADD45B	0.006	0.045	-10000	0	-0.5	3	3
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	0.015	0.17	3	-10000	0	3
RAC1/OSM/MEKK3	-0.001	0.013	-10000	0	-0.26	1	1
TRAF2	0.01	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.002	0.01	-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	-0.077	0.2	-10000	0	-0.52	64	64
CCM2	0.01	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.051	0.12	-10000	0	-0.31	64	64
MAPK11	0.006	0.045	-10000	0	-0.5	3	3
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.045	0.1	-10000	0	-0.28	64	64
OSM/MEKK3	-0.001	0.018	-10000	0	-0.35	1	1
TAOK1	0.014	0	-10000	0	-10000	0	0
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	0.006	0.045	-10000	0	-0.5	3	3
MAP3K3	0.009	0.026	-10000	0	-0.5	1	1
TRX/ASK1	0.011	0.012	-10000	0	-10000	0	0
GADD45/MTK1/MTK1	-0.006	0.041	-10000	0	-0.34	3	3

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	0.016	0.11	-9999	-0.53	3	3
MAP3K8	0.007	0.036	-9999	-0.5	2	2
FOS	0.02	0.072	-9999	-0.4	3	3
PRKCA	0.007	0.037	-9999	-0.51	2	2
PTPN7	0.011	0.003	-9999	-10000	0	0
HRAS	0.01	0.001	-9999	-10000	0	0
PRKCB	-0.002	0.077	-9999	-0.5	9	9
NRAS	0.01	0.001	-9999	-10000	0	0
RAS family/GTP	0	0	-9999	-10000	0	0
MAPK3	0.019	0.041	-9999	-10000	0	0
MAP2K1	0.017	0.078	-9999	-0.42	11	11
ELK1	0.009	0.006	-9999	-10000	0	0
BRAF	-0.013	0.064	-9999	-0.39	11	11
mol:GTP	0	0.001	-9999	-0.005	30	30
MAPK1	0.019	0.041	-9999	-10000	0	0
RAF1	-0.013	0.064	-9999	-0.39	11	11
KRAS	0.01	0.001	-9999	-10000	0	0

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	-0.023	0.079	-10000	0	-0.5	4	4
CLOCK	0.012	0.003	-10000	0	-10000	0	0
TIMELESS/CRY2	0.03	0.037	-10000	0	-10000	0	0
DEC1/BMAL1	0	0.001	-10000	0	-10000	0	0
ATR	0.01	0	-10000	0	-10000	0	0
NR1D1	0.032	0.021	-10000	0	-10000	0	0
ARNTL	0.012	0.003	-10000	0	-10000	0	0
TIMELESS	0.029	0.041	-10000	0	-10000	0	0
NPAS2	0.009	0.038	-10000	0	-0.51	2	2
CRY2	0.01	0	-10000	0	-10000	0	0
mol:CO	-0.01	0.009	0.064	6	-10000	0	6
CHEK1	-0.033	0.14	-10000	0	-0.52	32	32
mol:HEME	0.01	0.009	-10000	0	-0.064	6	6
PER1	-0.012	0.1	-10000	0	-0.5	17	17
BMAL/CLOCK/NPAS2	0.031	0.025	-10000	0	-0.3	2	2
BMAL1/CLOCK	0.034	0.036	-10000	0	-10000	0	0
S phase of mitotic cell cycle	-0.023	0.079	-10000	0	-0.5	4	4
TIMELESS/CHEK1/ATR	-0.023	0.08	-10000	0	-0.51	4	4
mol:NADPH	0.01	0.009	-10000	0	-0.064	6	6
PER1/TIMELESS	0.018	0.07	-10000	0	-0.52	1	1
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.002	0.004	-10000	0	-10000	0	0

×

JNK signaling in the CD4+ TCR 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
LAT/GRAP2/SLP76/HPK1	-0.013	0.075	-9999	-0.69	3	3
MAP4K1	0.003	0.057	-9999	-0.5	5	5
MAP3K8	0.007	0.036	-9999	-0.5	2	2
PRKCB	-0.002	0.076	-9999	-0.5	9	9
DBNL	0.01	0	-9999	-10000	0	0
CRKL	0.01	0	-9999	-10000	0	0
MAP3K1	0.025	0.07	-9999	-0.62	3	3
JUN	0.014	0.098	-9999	-0.59	9	9
MAP3K7	0.025	0.07	-9999	-0.62	3	3
GRAP2	-0.006	0.088	-9999	-0.5	12	12
CRK	0.01	0	-9999	-10000	0	0
MAP2K4	0.031	0.077	-9999	-0.71	3	3
LAT	0.008	0.027	-9999	-0.52	1	1
LCP2	0.007	0.036	-9999	-0.5	2	2
MAPK8	0.01	0.1	-9999	-0.63	9	9
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.02	0.074	-9999	-0.66	3	3
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.012	0.07	-9999	-0.65	3	3

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.03	0.012	-10000	0	-10000	0	0
regulation of axonogenesis	-0.023	0.004	-10000	0	-10000	0	0
myoblast fusion	0	0.011	-10000	0	-10000	0	0
mol:GTP	0	0.003	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.015	0.11	0.29	52	-10000	0	52
ARF1/GTP	0	0.001	-10000	0	-10000	0	0
mol:GM1	0.008	0.003	-10000	0	-10000	0	0
mol:Choline	0.023	0.003	-10000	0	-10000	0	0
lamellipodium assembly	0.011	0.032	-10000	0	-10000	0	0
MAPK3	0.02	0.008	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.015	0.11	-10000	0	-0.29	52	52
ARF1	0.01	0	-10000	0	-10000	0	0
ARF6/GDP	0	0.011	-10000	0	-10000	0	0
ARF1/GDP	0.027	0.017	-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	0.002	0.068	-10000	0	-0.5	7	7
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.02	0.008	-10000	0	-10000	0	0
actin filament bundle formation	0	0.006	-10000	0	-10000	0	0
KALRN	0.006	0.032	-10000	0	-0.26	3	3
RAB11FIP3/RAB11A	0	0	-10000	0	-10000	0	0
RhoA/GDP	0	0.006	-10000	0	-10000	0	0
NME1	-0.052	0.17	-10000	0	-0.52	47	47
Rac1/GDP	0	0.006	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0	0.003	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	0.011	0.032	-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	0.009	0.027	-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	0.004	-10000	0	-10000	0	0
RAB11FIP3	0.01	0	-10000	0	-10000	0	0
tube morphogenesis	0.011	0.032	-10000	0	-10000	0	0
ruffle organization	0.023	0.004	-10000	0	-10000	0	0
regulation of epithelial cell migration	0	0.003	-10000	0	-10000	0	0
PLD2	0.017	0.004	-10000	0	-10000	0	0
PIP5K1A	0.023	0.004	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.023	0.003	-10000	0	-10000	0	0
Rac1/GTP	0.011	0.032	-10000	0	-10000	0	0

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.018	0.059	-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	-0.014	0.045	-9999	-10000	0	0
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.004	0.018	-9999	-0.29	1	1
antigen processing and presentation of peptide antigen via MHC class I	-0.013	0.038	-9999	-0.28	1	1
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	0.059	-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	-0.055	0.11	-9999	-0.37	39	39
Rap1/GTP	-0.012	0.039	-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	0.045	0.081	-9999	-0.4	7	7
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)	-0.033	0.14	-9999	-0.51	33	33
PIK3CA	0.01	0	-9999	-10000	0	0
STAT1 (dimer)/PIAS1	0.022	0.062	-9999	-10000	0	0
CEBPB/PTGES2/Cbp/p300	-0.01	0.038	-9999	-0.34	1	1
mol:Ca2+	-0.018	0.059	-9999	-10000	0	0
MAPK3	0.034	0.06	-9999	-10000	0	0
STAT1 (dimer)	-0.016	0.051	-9999	-0.39	1	1
MAPK1	0.034	0.06	-9999	-10000	0	0
JAK2	0.008	0.026	-9999	-0.5	1	1
PIK3R1	0.01	0	-9999	-10000	0	0
JAK1	0.009	0.007	-9999	-10000	0	0
CAMK2D	0.01	0	-9999	-10000	0	0
DAPK1	0.04	0.095	-9999	-0.6	7	7
SMAD7	0.028	0.04	-9999	-0.26	1	1
CBL/CRKL/C3G	-0.015	0.048	-9999	-10000	0	0
PI3K	-0.016	0.051	-9999	-10000	0	0
IFNG	-0.033	0.14	-9999	-0.51	33	33
apoptosis	0.029	0.071	-9999	-0.43	7	7
CAMK2G	0.01	0	-9999	-10000	0	0
STAT3 (dimer)	0.01	0	-9999	-10000	0	0
CAMK2A	-0.042	0.16	-9999	-0.5	40	40
CAMK2B	-0.076	0.2	-9999	-0.52	64	64
FRAP1	0.026	0.056	-9999	-10000	0	0
PRKCD	0.027	0.06	-9999	-10000	0	0
RAP1B	0.01	0	-9999	-10000	0	0
negative regulation of cell growth	-0.013	0.038	-9999	-0.28	1	1
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	-0.016	0.051	-9999	-10000	0	0
SOCS1	0.002	0.007	-9999	-10000	0	0
mol:GDP	-0.014	0.046	-9999	-10000	0	0
CASP1	0.027	0.045	-9999	-0.28	3	3
PTGES2	0.01	0	-9999	-10000	0	0
IRF9	0.041	0.029	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.015	0.05	-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	0.065	-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	-0.013	0.038	-9999	-0.28	1	1
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

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.01	0	-10000	0	-10000	0	0
NFATC1	0.036	0.041	-10000	0	-0.4	1	1
NFATC2	0.013	0.045	-10000	0	-0.26	2	2
NFATC3	0.013	0.034	-10000	0	-0.37	3	3
YWHAE	0.01	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.012	0.094	-10000	0	-0.4	10	10
Exportin 1/Ran/NUP214	-0.002	0.022	-10000	0	-0.3	2	2
mol:DAG	-0.001	0.003	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.031	0.078	-10000	0	-0.39	11	11
BCL2/BAX	-0.002	0.026	-10000	0	-0.37	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.002	0.004	-10000	0	-10000	0	0
CaM/Ca2+	-0.002	0.004	-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	0.088	-10000	0	-0.38	10	10
Calcineurin A alpha-beta B1/BCL2	0.007	0.038	-10000	0	-0.52	2	2
FKBP8	0.009	0.026	-10000	0	-0.5	1	1
activation-induced cell death of T cells	0.011	0.087	0.38	10	-10000	0	10
KPNB1	0.01	0	-10000	0	-10000	0	0
KPNA2	0.003	0.059	-10000	0	-0.52	5	5
XPO1	0.01	0.001	-10000	0	-10000	0	0
SFN	-0.001	0.074	-10000	0	-0.52	8	8
MAP3K8	0.006	0.037	-10000	0	-0.5	2	2
NFAT4/CK1 alpha	-0.002	0.018	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.052	0.1	-10000	0	-0.39	5	5
CABIN1	-0.012	0.094	-10000	0	-0.41	10	10
CALM1	0.008	0.004	-10000	0	-10000	0	0
RAN	0.007	0.038	-10000	0	-0.52	2	2
MAP3K1	0.01	0	-10000	0	-10000	0	0
CAMK4	0.003	0.058	-10000	0	-0.5	5	5
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	0.025	-10000	0	-0.36	2	2
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	-0.005	0.037	-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	0.017	-10000	0	-10000	0	0
PRKCB	-0.002	0.076	-10000	0	-0.5	9	9
PRKCE	0.005	0.051	-10000	0	-0.5	4	4
JNK2/NFAT4	0.016	0.032	-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	0.004	0.045	-10000	0	-0.5	3	3
PRKCA	0.007	0.036	-10000	0	-0.5	2	2
PRKCG	-0.03	0.14	-10000	0	-0.52	28	28
PRKCQ	-0.064	0.18	-10000	0	-0.5	57	57
FKBP38/BCL2	-0.003	0.032	-10000	0	-0.36	3	3
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	0.042	-10000	0	-0.38	1	1
CaM/Ca2+/FKBP38	-0.001	0.016	-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	-0.004	0.034	-10000	0	-0.3	5	5
NFATc/ERK1	0.04	0.039	-10000	0	-0.38	1	1
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.031	0.077	-10000	0	-0.39	11	11
NR4A1	-0.053	0.21	-10000	0	-0.48	78	78
GSK3B	0.008	0.004	-10000	0	-10000	0	0
positive T cell selection	0.013	0.034	-10000	0	-0.37	3	3
NFAT1/CK1 alpha	-0.011	0.026	-10000	0	-0.26	1	1
RCH1/ KPNB1	-0.005	0.041	-10000	0	-0.37	5	5
YWHAQ	0.01	0	-10000	0	-10000	0	0
PRKACA	0.008	0.004	-10000	0	-10000	0	0
AKAP5	0.007	0.036	-10000	0	-0.5	2	2
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	0.042	-10000	0	-0.38	1	1
CREBBP	0.008	0.005	-10000	0	-10000	0	0
BCL2	0.007	0.038	-10000	0	-0.52	2	2

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.015	0.051	-9999	-10000	0	0
PLK1	-0.14	0.26	-9999	-0.6	37	37
CDKN1B	0.009	0.12	-9999	-10000	0	0
FOXO3	-0.082	0.21	-9999	-0.51	37	37
KAT2B	0.003	0.019	-9999	-10000	0	0
FOXO1/SIRT1	0.014	0.03	-9999	-10000	0	0
CAT	-0.076	0.23	-9999	-1.4	4	4
CTNNB1	0.01	0	-9999	-10000	0	0
AKT1	0.004	0.021	-9999	-10000	0	0
FOXO1	0.02	0.031	-9999	-10000	0	0
MAPK10	-0.007	0.091	-9999	-0.26	46	46
mol:GTP	0.002	0.001	-9999	-10000	0	0
FOXO4	0.049	0.067	-9999	-10000	0	0
response to oxidative stress	-0.009	0.024	-9999	-10000	0	0
FOXO3A/SIRT1	-0.12	0.16	-9999	-0.48	35	35
XPO1	0.01	0	-9999	-10000	0	0
EP300	0.01	0.004	-9999	-10000	0	0
BCL2L11	0.007	0.032	-9999	-10000	0	0
FOXO1/SKP2	0.02	0.04	-9999	-0.28	3	3
mol:GDP	-0.009	0.024	-9999	-10000	0	0
RAN	0.008	0.038	-9999	-0.52	2	2
GADD45A	0.002	0.12	-9999	-0.71	2	2
YWHAQ	0.01	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.055	0.017	-9999	-10000	0	0
MST1	-0.015	0.097	-9999	-0.53	13	13
CSNK1D	0.01	0	-9999	-10000	0	0
CSNK1E	0.01	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.042	0.023	-9999	-10000	0	0
YWHAB	0.01	0	-9999	-10000	0	0
MAPK8	0.025	0.01	-9999	-10000	0	0
MAPK9	0.024	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	0.005	0.14	-9999	-10000	0	0
RBL2	-0.03	0.15	-9999	-10000	0	0
RAL/GDP	0.012	0.015	-9999	-10000	0	0
CHUK	0.003	0.019	-9999	-10000	0	0
Ran/GTP	0.009	0.027	-9999	-0.37	2	2
CSNK1G2	0.01	0	-9999	-10000	0	0
RAL/GTP	0.018	0.016	-9999	-10000	0	0
CSNK1G1	0.01	0	-9999	-10000	0	0
FASLG	-0.009	0.15	-9999	-1.3	5	5
SKP2	0.004	0.053	-9999	-0.52	4	4
USP7	0.011	0.001	-9999	-10000	0	0
IKBKB	0.003	0.019	-9999	-10000	0	0
CCNB1	-0.11	0.25	-9999	-0.68	10	10
FOXO1-3a-4/beta catenin	-0.039	0.074	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.02	0.04	-9999	-0.27	3	3
CSNK1A1	0.01	0	-9999	-10000	0	0
SGK1	0.002	0.033	-9999	-0.53	1	1
CSNK1G3	0.01	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.017	0.023	-9999	-0.31	2	2
ZFAND5	0.053	0.059	-9999	-10000	0	0
SFN	-0.001	0.074	-9999	-0.52	8	8
CDK2	0.01	0.006	-9999	-10000	0	0
FOXO3A/14-3-3	0.02	0.048	-9999	-0.37	1	1
CREBBP	0.01	0.006	-9999	-10000	0	0
FBXO32	-0.089	0.22	-9999	-0.58	35	35
BCL6	-0.03	0.15	-9999	-10000	0	0
RALB	0.011	0	-9999	-10000	0	0
RALA	0.011	0	-9999	-10000	0	0
YWHAH	0.01	0	-9999	-10000	0	0

×

IL2 signaling events mediated by PI3K

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
BCL2L1	0.048	0.037	-10000	0	-10000	0	0
UGCG	-0.001	0.007	-10000	0	-10000	0	0
AKT1/mTOR/p70S6K/Hsp90/TERT	0.042	0.055	-10000	0	-0.31	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.022	0.012	-10000	0	-10000	0	0
mol:DAG	0	0.001	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.005	0.035	-10000	0	-0.31	4	4
FRAP1	0.065	0.055	-10000	0	-0.36	4	4
FOXO3	0.066	0.052	-10000	0	-0.36	3	3
AKT1	0.062	0.055	-10000	0	-0.38	3	3
GAB2	0.005	0.051	-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	0.002	-10000	0	-10000	0	0
CALM1	0.01	0	-10000	0	-10000	0	0
cell proliferation	0.04	0.029	-10000	0	-0.24	2	2
EIF3A	0.01	0	-10000	0	-10000	0	0
PI3K	0.02	0.003	-10000	0	-10000	0	0
RPS6KB1	0.022	0.019	-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	0.001	-10000	0	-10000	0	0
JAK1	0.012	0.001	-10000	0	-10000	0	0
NFKB1	0.01	0	-10000	0	-10000	0	0
MYC	0.061	0.081	-10000	0	-0.92	2	2
MYB	0.019	0.088	-10000	0	-1.2	2	2
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.055	0.051	-10000	0	-0.38	2	2
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.031	0.018	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.055	0.05	-10000	0	-0.37	2	2
Rac1/GDP	0.023	0.003	-10000	0	-10000	0	0
T cell proliferation	0.057	0.053	-10000	0	-0.37	2	2
SHC1	0.011	0.001	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.004	0.006	-10000	0	-0.046	5	5
PRKCZ	0.057	0.055	-10000	0	-0.38	2	2
NF kappa B1 p50/RelA	-0.004	0.034	-10000	0	-0.33	1	1
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	-0.031	0.14	-10000	0	-0.52	31	31
IL2RB	0.01	0.036	-10000	0	-0.5	2	2
TERT	-0.14	0.24	-10000	0	-0.52	107	107
E2F1	0.02	0.037	-10000	0	-0.42	2	2
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	0.022	5	-10000	0	5
PTPN11	0.011	0.001	-10000	0	-10000	0	0
IL2RG	0.007	0.052	-10000	0	-0.5	4	4
actin cytoskeleton organization	0.057	0.053	-10000	0	-0.37	2	2
GRB2	0.011	0.001	-10000	0	-10000	0	0
IL2	0.008	0.005	-10000	0	-10000	0	0
PIK3CA	0.012	0.001	-10000	0	-10000	0	0
Rac1/GTP	0.028	0.004	-10000	0	-10000	0	0
LCK	0.01	0.037	-10000	0	-0.51	2	2
BCL2	0.066	0.052	-10000	0	-0.42	1	1

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.009	0.026	-9999	-0.5	1	1
mol:S1P	0.001	0.003	-9999	-10000	0	0
S1P1/S1P/Gi	0.001	0.08	-9999	-0.23	37	37
GNAO1	0.006	0.053	-9999	-0.52	4	4
S1P/S1P3/G12/G13	-0.001	0.014	-9999	-0.28	1	1
AKT1	-0.009	0.038	-9999	-0.62	1	1
AKT3	0.021	0.11	-9999	-1.1	3	3
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.009	0.026	-9999	-0.5	1	1
GNAI2	0.011	0.002	-9999	-10000	0	0
GNAI3	0.011	0.002	-9999	-10000	0	0
GNAI1	0.008	0.036	-9999	-0.5	2	2
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.01	0.027	-9999	-0.52	1	1
S1PR2	0.01	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.011	0.075	-9999	-0.47	2	2
MAPK3	0.017	0.071	-9999	-0.45	2	2
MAPK1	0.017	0.071	-9999	-0.45	2	2
JAK2	0.02	0.072	-9999	-0.4	3	3
CXCR4	0.017	0.071	-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	0.017	0.071	-9999	-0.45	2	2
S1P/S1P3/Gi	0.011	0.076	-9999	-0.48	2	2
RAC1	0.01	0	-9999	-10000	0	0
RhoA/GTP	-0.019	0.057	-9999	-0.43	2	2
VEGFA	0.012	0.003	-9999	-10000	0	0
S1P/S1P2/Gi	0.009	0.072	-9999	-0.42	2	2
VEGFR1 homodimer/VEGFA homodimer	0.021	0.006	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
S1P/S1P3/Gq	0.016	0.054	-9999	-0.26	13	13
GNAQ	0.009	0.026	-9999	-0.5	1	1
GNAZ	-0.035	0.15	-9999	-0.5	35	35
G12/G13	0	0	-9999	-10000	0	0
GNA14	-0.006	0.088	-9999	-0.5	12	12
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	0.009	0.026	-9999	-0.5	1	1
Rac1/GTP	-0.019	0.057	-9999	-0.43	2	2

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.005	0.052	-10000	0	-0.51	4	4
positive regulation of NF-kappaB transcription factor activity	-0.005	0.044	-10000	0	-0.36	6	6
MAP2K4	0.035	0.024	-10000	0	-10000	0	0
IKBKB	0.01	0	-10000	0	-10000	0	0
TNFRSF10B	0.01	0	-10000	0	-10000	0	0
TNFRSF10A	0.007	0.036	-10000	0	-0.5	2	2
SMPD1	-0.002	0.018	-10000	0	-0.19	3	3
IKBKG	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.007	0.036	-10000	0	-0.5	2	2
TRAIL/TRAILR2	-0.004	0.036	-10000	0	-0.36	4	4
TRAIL/TRAILR3	-0.01	0.062	-10000	0	-0.39	10	10
TRAIL/TRAILR1	-0.005	0.044	-10000	0	-0.36	6	6
TRAIL/TRAILR4	-0.005	0.044	-10000	0	-0.36	6	6
TRAIL/TRAILR1/DAP3/GTP	-0.004	0.033	-10000	0	-0.27	6	6
IKK complex	-0.001	0.011	-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	0.038	-10000	0	-0.36	4	4
MAP3K1	-0.003	0.022	-10000	0	-10000	0	0
TRAILR4 (trimer)	0.007	0.036	-10000	0	-0.5	2	2
TRADD	0.01	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.007	0.036	-10000	0	-0.5	2	2
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.026	0.029	-10000	0	-10000	0	0
CFLAR	0.01	0	-10000	0	-10000	0	0
MAPK1	0.014	0.038	-10000	0	-0.36	4	4
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.004	0.029	-10000	0	-10000	0	0
mol:ceramide	-0.002	0.018	-10000	0	-0.19	3	3
FADD	0.01	0	-10000	0	-10000	0	0
MAPK8	0.04	0.023	-10000	0	-10000	0	0
TRAF2	0.01	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.001	0.068	-10000	0	-0.5	7	7
CHUK	0.01	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.004	0.036	-10000	0	-0.3	6	6
DAP3	0.01	0	-10000	0	-10000	0	0
CASP10	-0.003	0.035	0.24	1	-0.29	4	5
JNK cascade	-0.005	0.044	-10000	0	-0.36	6	6
TRAIL (trimer)	0.005	0.052	-10000	0	-0.5	4	4
TNFRSF10C	0.001	0.068	-10000	0	-0.5	7	7
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.004	0.03	-10000	0	-0.25	1	1
TRAIL/TRAILR2/FADD	-0.003	0.03	-10000	0	-0.3	4	4
cell death	-0.002	0.018	-10000	0	-0.19	3	3
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.027	0.023	-10000	0	-10000	0	0
TRAILR2 (trimer)	0.01	0	-10000	0	-10000	0	0
CASP8	-0.001	0.045	-10000	0	-0.87	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 S110. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.008	0.027	-9999	-0.52	1	1
Caspase 8 (4 units)	-0.006	0.041	-9999	-0.34	4	4
NEF	0.002	0.019	-9999	-10000	0	0
NFKBIA	0.011	0.012	-9999	-10000	0	0
BIRC3	0.028	0.063	-9999	-0.48	6	6
CYCS	0.036	0.046	-9999	-0.3	4	4
RIPK1	0.01	0	-9999	-10000	0	0
CD247	0.005	0.064	-9999	-0.53	5	5
MAP2K7	0.036	0.041	-9999	-0.31	3	3
protein ubiquitination	0.048	0.04	-9999	-10000	0	0
CRADD	0.008	0.027	-9999	-0.52	1	1
DAXX	0.01	0	-9999	-10000	0	0
FAS	0.005	0.051	-9999	-0.5	4	4
BID	0.031	0.048	-9999	-0.32	4	4
NF-kappa-B/RelA/I kappa B alpha	-0.004	0.03	-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	-0.004	0.03	-9999	-10000	0	0
MAPK8	0.04	0.039	-9999	-0.3	2	2
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	0.05	-9999	-0.29	9	9
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.04	0.047	-9999	-10000	0	0
CHUK	0.049	0.042	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.003	0.032	-9999	-0.49	1	1
TCRz/NEF	-0.008	0.056	-9999	-0.36	9	9
TNF	-0.02	0.12	-9999	-0.5	23	23
FASLG	0.011	0.081	-9999	-0.48	9	9
NFKB1	0.011	0.012	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.018	0.07	-9999	-0.29	24	24
CASP6	-0.005	0.038	-9999	-0.6	1	1
CASP7	0.061	0.062	-9999	-0.48	3	3
RELA	0.011	0.012	-9999	-10000	0	0
CASP2	0.01	0	-9999	-10000	0	0
CASP3	0.061	0.062	-9999	-0.48	3	3
TNFRSF1A	0.01	0	-9999	-10000	0	0
TNFR1A/BAG4	-0.001	0.019	-9999	-0.37	1	1
CASP8	0.009	0.026	-9999	-0.5	1	1
CASP9	0.01	0	-9999	-10000	0	0
MAP3K14	0.045	0.045	-9999	-10000	0	0
APAF-1/Caspase 9	-0.008	0.045	-9999	-0.48	1	1
BCL2	0.043	0.044	-9999	-0.31	3	3

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.005	0.051	-10000	0	-0.5	4	4
HRAS	0.01	0	-10000	0	-10000	0	0
EGFR	-0.007	0.093	-10000	0	-0.51	13	13
AKT	0.029	0.035	-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	0.006	0.045	-10000	0	-0.5	3	3
FOXO4	0.01	0	-10000	0	-10000	0	0
MET	-0.025	0.13	-10000	0	-0.51	26	26
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	-0.003	0.081	-10000	0	-0.5	10	10
PIK3R3	0.009	0.026	-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	0.008	0.046	-10000	0	-0.24	4	4
ERBB2	0.007	0.038	-10000	0	-0.52	2	2
proliferation/survival/translation	-0.021	0.028	0.2	3	-10000	0	3
PI3K	0.014	0.049	-10000	0	-0.22	6	6
PIK3R1	0.01	0	-10000	0	-10000	0	0
KRAS	0.01	0	-10000	0	-10000	0	0
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

×

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	0.032	-9999	-0.42	2	2
KLHL20	-0.014	0.036	-9999	-0.25	2	2
CYFIP2	0.002	0.063	-9999	-0.5	6	6
Rac1/GDP	0.05	0.023	-9999	-10000	0	0
ENAH	0.031	0.032	-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	0.012	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.01	0.025	-9999	-0.17	2	2
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.002	0.023	-9999	-0.26	3	3
RAPGEF1	0.041	0.028	-9999	-0.35	2	2
CTNND1	0.01	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.002	0.031	-9999	-0.43	2	2
CRK	0.037	0.031	-9999	-0.39	2	2
E-cadherin/gamma catenin/alpha catenin	-0.002	0.026	-9999	-0.3	3	3
alphaE/beta7 Integrin	-0.001	0.018	-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	0.031	0.032	-9999	-0.42	2	2
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.008	-9999	-10000	0	0
MLLT4	0.01	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.038	0.099	-9999	-0.29	52	52
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	-0.003	0.031	-9999	-0.36	3	3
TIAM1	0.001	0.068	-9999	-0.5	7	7
E-cadherin(dimer)/Ca2+	-0.001	0.017	-9999	-10000	0	0
AKT1	0	0.006	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
CDH1	0.007	0.036	-9999	-0.5	2	2
RhoA/GDP	0.05	0.022	-9999	-10000	0	0
actin cytoskeleton organization	-0.01	0.027	-9999	-0.18	2	2
CDC42/GDP	0.05	0.022	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.018	0.019	-9999	-0.23	2	2
ITGB7	0.009	0.026	-9999	-0.5	1	1
RAC1	0.01	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.001	0.018	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.001	0.018	-9999	-0.25	2	2
mol:GDP	0.049	0.025	-9999	-10000	0	0
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	0.008	0.027	-9999	-0.52	1	1
p120 catenin/RhoA/GDP	-0.001	0.017	-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	0.017	0.035	-9999	-0.21	5	5
NME1	-0.053	0.17	-9999	-0.52	47	47
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.031	0.032	-9999	-0.42	2	2
regulation of cell-cell adhesion	-0.001	0.01	-9999	-10000	0	0
WASF2	-0.005	0.013	-9999	-10000	0	0
Rap1/GTP	-0.001	0.013	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.002	0.024	-9999	-10000	0	0
CCND1	0.019	0.043	-9999	-0.26	5	5
VAV2	0.038	0.046	-9999	-0.47	3	3
RAP1/GDP	-0.001	0.015	-9999	-10000	0	0
adherens junction assembly	0.031	0.031	-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	0.022	-9999	-10000	0	0
E-cadherin/beta catenin	-0.002	0.024	-9999	-0.34	2	2
mol:GTP	0	0	-9999	-10000	0	0
SRC	0.031	0.032	-9999	-0.42	2	2
PIK3CA	0.01	0	-9999	-10000	0	0
Rac1/GTP	-0.021	0.057	-9999	-0.42	2	2
E-cadherin/beta catenin/alpha catenin	-0.001	0.021	-9999	-0.29	2	2
ITGAE	0.01	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.002	0.031	-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	0.017	0.039	-10000	0	-0.28	6	6
GRB2/SOS1/SHC	0	0	-10000	0	-10000	0	0
HRAS	0.01	0	-10000	0	-10000	0	0
IRS1/Crk	0.016	0.039	-10000	0	-0.28	6	6
IGF-1R heterotetramer/IGF1/PTP1B	-0.005	0.038	-10000	0	-0.28	7	7
AKT1	0.032	0.034	-10000	0	-0.38	1	1
BAD	0.037	0.032	-10000	0	-0.36	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.017	0.039	-10000	0	-0.28	6	6
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.005	0.037	-10000	0	-0.28	6	6
RAF1	0.04	0.031	-10000	0	-0.34	1	1
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.004	0.034	-10000	0	-0.44	1	1
YWHAZ	0.01	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.005	0.04	-10000	0	-0.29	7	7
PIK3CA	0.01	0	-10000	0	-10000	0	0
RPS6KB1	0.032	0.034	-10000	0	-0.38	1	1
GNB2L1	0.01	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	0.035	0.028	-10000	0	-0.3	1	1
PXN	0.01	0	-10000	0	-10000	0	0
PIK3R1	0.01	0	-10000	0	-10000	0	0
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
HRAS/GTP	-0.004	0.03	-10000	0	-0.39	1	1
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.004	0.028	-10000	0	-10000	0	0
IGF-1R heterotetramer	0.008	0.028	-10000	0	-0.51	1	1
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.005	0.037	-10000	0	-0.28	6	6
Crk/p130 Cas/Paxillin	-0.005	0.034	-10000	0	-0.41	1	1
IGF1R	0.008	0.028	-10000	0	-0.51	1	1
IGF1	0.002	0.065	-10000	0	-0.52	6	6
IRS2/Crk	0.021	0.039	-10000	0	-0.43	1	1
PI3K	-0.004	0.034	-10000	0	-0.43	1	1
apoptosis	-0.039	0.029	0.31	1	-10000	0	1
HRAS/GDP	0	0	-10000	0	-10000	0	0
PRKCD	0.028	0.047	-10000	0	-0.36	5	5
RAF1/14-3-3 E	0.042	0.028	-10000	0	-10000	0	0
BAD/14-3-3	0.041	0.03	-10000	0	-0.33	1	1
PRKCZ	0.031	0.04	-10000	0	-0.38	1	1
Crk/p130 Cas/Paxillin/FAK1	-0.003	0.025	-10000	0	-0.32	1	1
PTPN1	0.01	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.022	0.049	-10000	0	-0.36	6	6
BCAR1	0.009	0.026	-10000	0	-0.5	1	1
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.004	0.032	-10000	0	-0.29	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.01	0	-10000	0	-10000	0	0
IRS1/NCK2	0.016	0.039	-10000	0	-0.28	6	6
GRB10	0.01	0	-10000	0	-10000	0	0
PTPN11	0.017	0.039	-10000	0	-0.28	6	6
IRS1	0.01	0.042	-10000	0	-0.29	7	7
IRS2	0.016	0.041	-10000	0	-0.27	7	7
IGF-1R heterotetramer/IGF1	-0.007	0.05	-10000	0	-0.38	7	7
GRB2	0.01	0	-10000	0	-10000	0	0
PDPK1	0.027	0.036	-10000	0	-0.41	1	1
YWHAE	0.01	0	-10000	0	-10000	0	0
PRKD1	0.017	0.072	-10000	0	-0.41	5	5
SHC1	0.01	0	-10000	0	-10000	0	0

×

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	-0.006	0.04	-10000	0	-0.25	10	10
MAPK9	0.007	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	0	0.033	-10000	0	-0.38	3	3
GNB1/GNG2	-0.001	0.015	-10000	0	-0.3	1	1
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	9	9
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	9	-10000	0	9
GNAL	-0.002	0.078	-10000	0	-0.51	9	9
GNG2	0.009	0.026	-10000	0	-0.5	1	1
CRH	-0.001	0.046	-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	0.004	0.029	-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	-0.004	0.036	-9999	-0.55	1	1
PDGFB-D/PDGFRB/SLAP	-0.009	0.06	-9999	-0.39	9	9
PDGFB-D/PDGFRB/APS/CBL	-0.002	0.021	-9999	-0.3	2	2
AKT1	0.045	0.03	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.024	0.044	-9999	-0.59	1	1
PIK3CA	0.01	0	-9999	-10000	0	0
FGR	-0.041	0.14	-9999	-0.51	33	33
mol:Ca2+	0.022	0.041	-9999	-0.63	1	1
MYC	0.031	0.076	-9999	-0.68	3	3
SHC1	0.01	0	-9999	-10000	0	0
HRAS/GDP	0.002	0.014	-9999	-10000	0	0
LRP1/PDGFRB/PDGFB	-0.008	0.062	-9999	-0.4	8	8
GRB10	0.01	0	-9999	-10000	0	0
PTPN11	0.01	0	-9999	-10000	0	0
GO:0007205	0.022	0.042	-9999	-0.65	1	1
PTEN	0.01	0	-9999	-10000	0	0
GRB2	0.01	0	-9999	-10000	0	0
GRB7	0.003	0.058	-9999	-0.51	5	5
PDGFB-D/PDGFRB/SHP2	0	0.018	-9999	-0.36	1	1
PDGFB-D/PDGFRB/GRB10	0	0.018	-9999	-0.36	1	1
cell cycle arrest	-0.009	0.06	-9999	-0.39	9	9
HRAS	0.01	0	-9999	-10000	0	0
HIF1A	0.049	0.028	-9999	-10000	0	0
GAB1	0.02	0.052	-9999	-0.64	1	1
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.025	0.048	-9999	-0.57	1	1
PDGFB-D/PDGFRB	0.005	0.019	-9999	-0.31	1	1
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0	0.018	-9999	-0.36	1	1
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.004	0.036	-9999	-0.51	1	1
positive regulation of MAPKKK cascade	0	0.018	-9999	-0.36	1	1
PIK3R1	0.01	0	-9999	-10000	0	0
mol:IP3	0.022	0.042	-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	0.045	-9999	-0.36	6	6
SHB	0.009	0.026	-9999	-0.5	1	1
BLK	-0.014	0.057	-9999	-0.47	5	5
PTPN2	0.01	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0	0.018	-9999	-0.36	1	1
BCAR1	0.009	0.026	-9999	-0.5	1	1
VAV2	0.02	0.069	-9999	-0.55	2	2
CBL	0.01	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0	0.018	-9999	-0.36	1	1
LCK	0	0.031	-9999	-0.41	2	2
PDGFRB	0.009	0.026	-9999	-0.51	1	1
ACP1	0.01	0	-9999	-10000	0	0
HCK	-0.019	0.11	-9999	-0.54	16	16
ABL1	0.017	0.053	-9999	-0.6	1	1
PDGFB-D/PDGFRB/CBL	0.018	0.058	-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	0.031	0.069	-9999	-0.6	3	3
SLA	-0.002	0.076	-9999	-0.5	9	9
actin cytoskeleton reorganization	0.007	0.026	-9999	-10000	0	0
SRC	0.002	0.019	-9999	-0.34	1	1
PI3K	-0.003	0.026	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	-0.005	0.037	-9999	-0.3	6	6
SH2B2	0.009	0.026	-9999	-0.5	1	1
PLCgamma1/SPHK1	0.025	0.045	-9999	-0.62	1	1
LYN	0.002	0.019	-9999	-0.34	1	1
LRP1	0.005	0.051	-9999	-0.5	4	4
SOS1	0.01	0	-9999	-10000	0	0
STAT5B	0.01	0	-9999	-10000	0	0
STAT5A	0.009	0.026	-9999	-0.5	1	1
NCK1-2/p130 Cas	0.002	0.019	-9999	-10000	0	0
SPHK1	0.006	0.046	-9999	-0.52	3	3
EDG1	0.001	0.001	-9999	-10000	0	0
mol:DAG	0.022	0.042	-9999	-0.65	1	1
PLCG1	0.022	0.043	-9999	-0.67	1	1
NHERF/PDGFRB	-0.005	0.039	-9999	-0.3	7	7
YES1	0.002	0.019	-9999	-0.34	1	1
cell migration	-0.005	0.039	-9999	-0.3	7	7
SHC/Grb2/SOS1	0.002	0.015	-9999	-10000	0	0
SLC9A3R2	0.005	0.051	-9999	-0.5	4	4
SLC9A3R1	0.007	0.038	-9999	-0.52	2	2
NHERF1-2/PDGFRB/PTEN	-0.005	0.035	-9999	-0.26	7	7
FYN	0.001	0.032	-9999	-0.43	2	2
DOK1	0.026	0.015	-9999	-0.27	1	1
HRAS/GTP	0	0	-9999	-10000	0	0
PDGFB	0.002	0.063	-9999	-0.5	6	6
RAC1	0.029	0.07	-9999	-0.53	3	3
PRKCD	0.027	0.015	-9999	-0.27	1	1
FER	0.027	0.015	-9999	-0.27	1	1
MAPKKK cascade	-0.001	0.011	-9999	-10000	0	0
RASA1	0.027	0.015	-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	0.018	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHB	-0.001	0.026	-9999	-0.36	2	2
chemotaxis	0.017	0.052	-9999	-0.58	1	1
STAT1-3-5/STAT1-3-5	-0.001	0.015	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	-0.001	0.019	-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	0.014	-9999	-10000	0	0
ERC1	0.01	0	-9999	-10000	0	0
RIP2/NOD2	-0.001	0.018	-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	0.009	-9999	-10000	0	0
IKK complex/A20	-0.011	0.045	-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	0.01	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.007	0.038	-9999	-0.52	2	2
Exportin 1/RanGTP	-0.002	0.022	-9999	-0.31	2	2
IKK complex/ELKS	0	0.007	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0	0	-9999	-10000	0	0
NOD2	0.009	0.026	-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	-0.021	0.083	-9999	-0.36	23	23
TRAF6	0.01	0	-9999	-10000	0	0
PRKCA	0.007	0.036	-9999	-0.5	2	2
CHUK	0.01	0	-9999	-10000	0	0
UBE2D3	0.01	0	-9999	-10000	0	0
TNF	-0.02	0.12	-9999	-0.5	23	23
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	0.008	-9999	-10000	0	0
CYLD	0.01	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.001	0.015	-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	0.026	-9999	-0.5	1	1
ITGA4	0.007	0.036	-9999	-0.5	2	2
alpha4/beta7 Integrin	-0.003	0.031	-9999	-0.35	3	3
alpha4/beta1 Integrin	-0.002	0.025	-9999	-0.35	2	2

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.022	0.029	-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	0.007	0.036	-9999	-0.5	2	2
alpha4/beta7 Integrin/MAdCAM1	-0.005	0.035	-9999	-0.27	7	7
EPO	0.002	0.046	-9999	-0.52	3	3
alpha4/beta7 Integrin	-0.003	0.031	-9999	-0.35	3	3
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.002	0.025	-9999	-0.35	2	2
EPO/EPOR (dimer)	-0.003	0.032	-9999	-0.37	3	3
lamellipodium assembly	0	0.003	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
ARF6	0.01	0	-9999	-10000	0	0
JAK2	0.005	0.03	-9999	-0.32	1	1
PXN	0.01	0	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
MADCAM1	0.003	0.053	-9999	-0.52	4	4
cell adhesion	-0.005	0.035	-9999	-0.26	7	7
CRKL/CBL	0	0	-9999	-10000	0	0
ITGB1	0.01	0	-9999	-10000	0	0
SRC	0.022	0.035	-9999	-0.27	1	1
ITGB7	0.009	0.026	-9999	-0.5	1	1
RAC1	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.004	0.036	-9999	-0.3	6	6
p130Cas/Crk/Dock1	-0.004	0.027	-9999	-10000	0	0
VCAM1	0.005	0.052	-9999	-0.51	4	4
RHOA	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.001	0.018	-9999	-10000	0	0
BCAR1	0.028	0.036	-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	0.003	-9999	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.029	0.052	-9999	-0.42	1	1
BAG4	0.008	0.027	-9999	-0.52	1	1
BAD	0.022	0.022	-9999	-10000	0	0
NFKBIA	0.01	0	-9999	-10000	0	0
BIRC3	0.002	0.064	-9999	-0.51	6	6
BAX	0.022	0.022	-9999	-10000	0	0
EnzymeConsortium:3.1.4.12	0.01	0.016	-9999	-0.099	1	1
IKBKB	0.034	0.05	-9999	-0.39	1	1
MAP2K2	0.031	0.025	-9999	-10000	0	0
MAP2K1	0.031	0.025	-9999	-10000	0	0
SMPD1	0.014	0.016	-9999	-10000	0	0
GO:0005551	0	0	-9999	-10000	0	0
FADD/Caspase 8	0.034	0.053	-9999	-0.35	2	2
MAP2K4	0.027	0.022	-9999	-10000	0	0
protein ubiquitination	0.036	0.051	-9999	-0.4	1	1
EnzymeConsortium:2.7.1.37	0.035	0.028	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
RAF1	0.027	0.024	-9999	-10000	0	0
CRADD	0.009	0.027	-9999	-0.52	1	1
mol:ceramide	0.017	0.022	-9999	-0.14	1	1
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-9999	-10000	0	0
MADD	0.01	0	-9999	-10000	0	0
MAP3K1	0.022	0.022	-9999	-10000	0	0
TRADD	0.01	0	-9999	-10000	0	0
RELA/p50	0.01	0	-9999	-10000	0	0
MAPK3	0.033	0.025	-9999	-10000	0	0
MAPK1	0.033	0.025	-9999	-10000	0	0
p50/RELA/I-kappa-B-alpha	0	0	-9999	-10000	0	0
FADD	0.029	0.052	-9999	-0.42	1	1
KSR1	0.022	0.023	-9999	-10000	0	0
MAPK8	0.032	0.021	-9999	-10000	0	0
TRAF2	0.01	0	-9999	-10000	0	0
response to radiation	0	0	-9999	-10000	0	0
CHUK	0.034	0.05	-9999	-0.39	1	1
TNF R/SODD	-0.001	0.019	-9999	-0.37	1	1
TNF	-0.02	0.12	-9999	-0.5	23	23
CYCS	0.023	0.021	-9999	-10000	0	0
IKBKG	0.034	0.05	-9999	-0.39	1	1
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.024	0.054	-9999	-0.35	2	2
RELA	0.01	0	-9999	-10000	0	0
RIPK1	0.01	0	-9999	-10000	0	0
AIFM1	0.023	0.021	-9999	-10000	0	0
TNF/TNF R/SODD	-0.018	0.07	-9999	-0.29	24	24
TNFRSF1A	0.01	0	-9999	-10000	0	0
response to heat	0	0	-9999	-10000	0	0
CASP8	0.019	0.038	-9999	-0.68	1	1
NSMAF	0.029	0.052	-9999	-0.41	1	1
response to hydrogen peroxide	0	0	-9999	-10000	0	0
BCL2	0.007	0.038	-9999	-0.52	2	2

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.002	0.026	-9999	-0.3	3	3
E-cadherin/beta catenin	-0.002	0.025	-9999	-0.35	2	2
CTNNB1	0.01	0	-9999	-10000	0	0
JUP	0.008	0.027	-9999	-0.52	1	1
CDH1	0.007	0.036	-9999	-0.5	2	2

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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
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	0.025	-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	-0.002	0.025	-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	0.007	0.036	-9999	-0.5	2	2
UBE2I	0.01	0	-9999	-10000	0	0
NUP153	0.01	0	-9999	-10000	0	0
KPNA2	0.003	0.059	-9999	-0.52	5	5
PIAS4	0.01	0	-9999	-10000	0	0

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.061	0.027	-10000	0	-10000	0	0
CRKL	0.035	0.029	-10000	0	-10000	0	0
mol:DAG	0.04	0.023	-10000	0	-10000	0	0
HRAS	0.052	0.028	-10000	0	-10000	0	0
MAPK8	0.027	0.024	-10000	0	-10000	0	0
RAP1A	0.035	0.029	-10000	0	-10000	0	0
GAB1	0.034	0.032	-10000	0	-10000	0	0
MAPK14	0.027	0.024	-10000	0	-10000	0	0
EPO	0.005	0.046	-10000	0	-0.51	3	3
PLCG1	0.04	0.024	-10000	0	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0.012	0.003	-10000	0	-10000	0	0
RAPGEF1	0.01	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.004	0.033	-10000	0	-0.29	5	5
GAB1/SHC/GRB2/SOS1	-0.003	0.022	-10000	0	-10000	0	0
EPO/EPOR (dimer)	0.014	0.033	-10000	0	-0.36	3	3
IRS2	0.034	0.036	-10000	0	-0.44	1	1
STAT1	0.048	0.025	-10000	0	-10000	0	0
STAT5B	0.044	0.024	-10000	0	-10000	0	0
cell proliferation	0.032	0.022	-10000	0	-10000	0	0
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.004	0.029	-10000	0	-0.37	1	1
TEC	0.035	0.029	-10000	0	-10000	0	0
SOCS3	0.007	0.036	-10000	0	-0.5	2	2
STAT1 (dimer)	0.048	0.025	-10000	0	-10000	0	0
JAK2	0.01	0.026	-10000	0	-0.5	1	1
PIK3R1	0.01	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.039	0.032	-10000	0	-10000	0	0
EPO/EPOR	0.014	0.033	-10000	0	-0.36	3	3
LYN	0.011	0.001	-10000	0	-10000	0	0
TEC/VAV2	0.04	0.031	-10000	0	-10000	0	0
elevation of cytosolic calcium ion concentration	0.012	0.003	-10000	0	-10000	0	0
SHC1	0.01	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	0.025	0.027	-10000	0	-0.28	3	3
mol:IP3	0.04	0.023	-10000	0	-10000	0	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.005	0.036	-10000	0	-0.4	2	2
SH2B3	0.009	0.036	-10000	0	-0.5	2	2
NFKB1	0.027	0.024	-10000	0	-10000	0	0
EPO/EPOR (dimer)/JAK2/SOCS3	-0.002	0.029	0.24	2	-0.25	1	3
PTPN6	0.03	0.03	-10000	0	-10000	0	0
TEC/VAV2/GRB2	0.014	0.034	-10000	0	-10000	0	0
EPOR	0.012	0.003	-10000	0	-10000	0	0
INPP5D	0.006	0.045	-10000	0	-0.5	3	3
mol:GDP	-0.003	0.022	-10000	0	-10000	0	0
SOS1	0.01	0	-10000	0	-10000	0	0
PLCG2	0.006	0.045	-10000	0	-0.5	3	3
CRKL/CBL/C3G	0.014	0.032	-10000	0	-10000	0	0
VAV2	0.034	0.032	-10000	0	-10000	0	0
CBL	0.035	0.029	-10000	0	-10000	0	0
SHC/Grb2/SOS1	-0.003	0.021	-10000	0	-10000	0	0
STAT5A	0.044	0.035	-10000	0	-0.49	1	1
GRB2	0.01	0	-10000	0	-10000	0	0
STAT5 (dimer)	0.058	0.036	-10000	0	-0.44	1	1
LYN/PLCgamma2	-0.003	0.031	-10000	0	-0.35	3	3
PTPN11	0.01	0	-10000	0	-10000	0	0
BTK	0.019	0.074	-10000	0	-0.4	4	4
BCL2	0.06	0.034	-10000	0	-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	-0.004	0.03	-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	0.031	0.04	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	0.027	-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	0.006	0.045	-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	0.019	-10000	0	-10000	0	0
VAMP2	0.01	0	-10000	0	-10000	0	0
SLC2A4	0.032	0.043	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	-0.001	0.074	-10000	0	-0.52	8	8
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	0.013	-10000	0	-0.27	1	1
FRAP1	0.012	0.003	-10000	0	-10000	0	0
AKT1	-0.001	0.011	-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	0.008	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0	0.002	-10000	0	-10000	0	0
TSC2	0.01	0	-10000	0	-10000	0	0
RHEB/GDP	-0.001	0.012	-10000	0	-10000	0	0
TSC1	0.01	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.012	0.017	-10000	0	-0.32	1	1
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0	0.003	-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	0.007	-10000	0	-10000	0	0
MAP3K5	0.008	0	-10000	0	-10000	0	0
PIK3R1	0.01	0	-10000	0	-10000	0	0
apoptosis	0.008	0	-10000	0	-10000	0	0
mol:LY294002	0	0	-10000	0	-0.001	1	1
EIF4B	0.027	0.006	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0	0.004	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	0	0	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.018	0.016	-10000	0	-0.29	1	1
mTOR/RHEB/GTP/Raptor/GBL	0.025	0.008	-10000	0	-10000	0	0
FKBP1A	0.01	0	-10000	0	-10000	0	0
RHEB/GTP	-0.001	0.012	-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	0.012	-10000	0	-0.24	1	1
EIF4E	0.01	0	-10000	0	-10000	0	0
ASK1/PP5C	0.017	0.002	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.013	0.007	-10000	0	-10000	0	0
TSC1/TSC2	0	0.009	-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	0.018	-10000	0	-0.35	1	1
INS	0	0	-10000	0	-10000	0	0
PTEN	0.009	0	-10000	0	-10000	0	0
PDK2	-0.001	0.012	-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	0.003	-10000	0	-10000	0	0
peptide biosynthetic process	0.014	0	-10000	0	-10000	0	0
RHEB	0.009	0.027	-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	0.01	-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	0.013	-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	0.011	0.029	-9999	-0.32	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	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	0.013	-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	-0.001	0.011	-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	0.013	-9999	-10000	0	0
PDPK1	0.01	0	-9999	-10000	0	0
MDM2	0.028	0.019	-9999	-10000	0	0
MAPKKK cascade	-0.029	0	-9999	-10000	0	0
MDM2/Cbp/p300	0.037	0.018	-9999	-10000	0	0
TSC1/TSC2	0.035	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.001	0.014	-9999	-10000	0	0
glucose import	0.021	0.032	-9999	-0.26	5	5
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.025	0.004	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	0.021	0.032	-9999	-0.26	5	5
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	-0.001	0.074	-9999	-0.52	8	8
G1/S transition of mitotic cell cycle	0.035	0	-9999	-10000	0	0
p27Kip1/14-3-3 family	0.036	0.018	-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	0.008	0.027	-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	0.007	0.036	-9999	-0.5	2	2
RAC1	0.01	0	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.003	0.031	-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	0.021	-9999	-0.29	2	2
alpha4/beta7 Integrin/Paxillin	-0.002	0.022	-9999	-10000	0	0
lamellipodium assembly	0	0.012	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
ARF6	0.01	0	-9999	-10000	0	0
TLN1	0.009	0.026	-9999	-0.5	1	1
PXN	0.018	0	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
ARF6/GTP	-0.001	0.015	-9999	-10000	0	0
cell adhesion	-0.002	0.02	-9999	-10000	0	0
CRKL/CBL	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	-0.001	0.018	-9999	-10000	0	0
ITGB1	0.01	0	-9999	-10000	0	0
ITGB7	0.009	0.026	-9999	-0.5	1	1
ARF6/GDP	0	0.003	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.004	0.029	-9999	-10000	0	0
p130Cas/Crk/Dock1	-0.001	0.015	-9999	-0.29	1	1
VCAM1	0.005	0.052	-9999	-0.51	4	4
alpha4/beta1 Integrin/Paxillin/Talin	-0.002	0.021	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.001	0.017	-9999	-10000	0	0
BCAR1	0.009	0.026	-9999	-0.5	1	1
mol:GDP	0.001	0.017	-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	-0.002	0.021	-9999	-10000	0	0
Rac1/GTP	0	0.013	-9999	-10000	0	0

×

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	0.018	-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	4	4
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	0.016	-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	0.01	0	-9999	-10000	0	0
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	0	-9999	-10000	0	0
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	0.006	0.045	-9999	-0.5	3	3
I kappa B alpha/PIK3R1	0.025	0.021	-9999	-10000	0	0
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	0.037	-9999	-0.51	2	2
BCL3	0.009	0.026	-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	-0.002	0.018	-9999	-10000	0	0
MDM2/SUMO1	-0.001	0.017	-9999	-0.24	2	2
HDAC4	0.008	0.027	-9999	-0.52	1	1
Ran/GTP/Exportin 1/HDAC1	-0.001	0.015	-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	0.007	0.038	-9999	-0.52	2	2
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.01	0	-9999	-10000	0	0
SUMO1/HDAC4	-0.001	0.012	-9999	-0.24	1	1
SUMO1/HDAC1	0	0	-9999	-10000	0	0
RANGAP1	0.01	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	-0.001	0.019	-9999	-0.27	2	2
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.017	0	-9999	-10000	0	0
Ran/GTP	-0.001	0.017	-9999	-0.24	2	2
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.007	0.038	-9999	-0.52	2	2
UBE2I	0.01	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	-0.001	0.016	-9999	-0.23	2	2
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	0.011	-9999	-10000	0	0
adherens junction organization	0.032	0.026	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
Rac1/GDP	0.035	0.045	-9999	-10000	0	0
FMN1	0.025	0.049	-9999	-10000	0	0
mol:IP3	-0.001	0.009	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.029	0.02	-9999	-0.23	2	2
CTNNB1	0.01	0.001	-9999	-10000	0	0
AKT1	0.038	0.013	-9999	-10000	0	0
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.029	0.031	-9999	-0.36	2	2
CTNND1	0.011	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.034	0.019	-9999	-10000	0	0
VASP	0.034	0.019	-9999	-10000	0	0
ZYX	0.034	0.019	-9999	-10000	0	0
JUB	0.033	0.026	-9999	-10000	0	0
EGFR(dimer)	0.024	0.051	-9999	-0.32	1	1
E-cadherin/beta catenin-gamma catenin	-0.002	0.025	-9999	-0.29	3	3
mol:PI-3-4-5-P3	-0.001	0.011	-9999	-10000	0	0
PIK3CA	0.011	0	-9999	-10000	0	0
PI3K	-0.001	0.011	-9999	-10000	0	0
FYN	0.023	0.061	-9999	-10000	0	0
mol:Ca2+	-0.001	0.008	-9999	-10000	0	0
JUP	0.008	0.027	-9999	-0.52	1	1
PIK3R1	0.011	0	-9999	-10000	0	0
mol:DAG	-0.001	0.009	-9999	-10000	0	0
CDH1	0.007	0.036	-9999	-0.5	2	2
RhoA/GDP	0.035	0.045	-9999	-10000	0	0
establishment of polarity of embryonic epithelium	0.034	0.019	-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	-0.007	0.093	-9999	-0.51	13	13
CASR	0.014	0.073	-9999	-10000	0	0
RhoA/GTP	-0.001	0.007	-9999	-10000	0	0
AKT2	0.038	0.013	-9999	-10000	0	0
actin cable formation	0.031	0.048	-9999	-10000	0	0
apoptosis	0.001	0.01	-9999	-10000	0	0
CTNNA1	0.011	0	-9999	-10000	0	0
mol:GDP	0.031	0.047	-9999	-0.29	1	1
PIP5K1A	0.034	0.019	-9999	-10000	0	0
PLCG1	-0.001	0.009	-9999	-10000	0	0
Rac1/GTP	-0.008	0.04	-9999	-0.3	1	1
homophilic cell adhesion	0.001	0	-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	-0.001	0.072	-9999	-0.5	8	8
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	0.021	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	-10000	0	0
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	8	8

×

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.J2.8194	TCGA.J2.8192	TCGA.99.8033	TCGA.99.8032
109_MAP3K5	0.043	0.043	0.043	0.043
47_PPARGC1A	0.0098	0.0098	0.0098	0.0098
105_BMP4	0.0098	0.0098	0.0098	0.0098
105_BMP6	0.0098	0.0098	0.0098	0.0098
105_BMP7	0.0098	0.0098	-0.5	0.0098
105_BMP2	0.0098	0.0098	0.0098	0.0098
131_RELN/VLDLR	0	0	0	0
30_TGFB1/TGF beta receptor Type II	0.0096	0.0093	0.0094	0.014
84_STAT5B	-0.03	-0.03	-0.01	0.024
84_STAT5A	-0.03	-0.03	-0.01	0.024