PARADIGM pathway analysis of mRNA expression data

Pathway.Name	Avg.Num.Perturbations
HIF-1-alpha transcription factor network	145
Syndecan-4-mediated signaling events	101
FOXM1 transcription factor network	91
Angiopoietin receptor Tie2-mediated signaling	78
Endothelins	73
EGFR-dependent Endothelin signaling events	73
Syndecan-1-mediated signaling events	69
HIF-2-alpha transcription factor network	68
Wnt signaling	68
PDGFR-alpha signaling pathway	67

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
HIF-1-alpha transcription factor network	0.2746	145	11053	76	-0.37	0.022	1000	-1000	-0.035	-1000
Syndecan-4-mediated signaling events	0.1913	101	6832	67	-0.18	0.022	1000	-1000	-0.01	-1000
FOXM1 transcription factor network	0.1723	91	4681	51	-0.42	0.019	1000	-1000	-0.11	-1000
Angiopoietin receptor Tie2-mediated signaling	0.1477	78	6944	88	-0.31	0.066	1000	-1000	-0.048	-1000
Endothelins	0.1383	73	7074	96	-0.17	0.042	1000	-1000	-0.012	-1000
EGFR-dependent Endothelin signaling events	0.1383	73	1546	21	-0.08	0.014	1000	-1000	0	-1000
Syndecan-1-mediated signaling events	0.1307	69	2354	34	-0.096	0.019	1000	-1000	-0.002	-1000
HIF-2-alpha transcription factor network	0.1288	68	2959	43	-0.17	0.13	1000	-1000	-0.068	-1000
Wnt signaling	0.1288	68	476	7	-0.033	0.019	1000	-1000	0.002	-1000
PDGFR-alpha signaling pathway	0.1269	67	2986	44	-0.12	0.02	1000	-1000	-0.001	-1000
LPA receptor mediated events	0.1269	67	6935	102	-0.2	0.019	1000	-1000	-0.024	-1000
Glypican 2 network	0.1250	66	267	4	-0.025	0	1000	-1000	0	-1000
S1P4 pathway	0.1174	62	1566	25	-0.047	0.017	1000	-1000	0	-1000
Fc-epsilon receptor I signaling in mast cells	0.1136	60	5876	97	-0.076	0.021	1000	-1000	-0.024	-1000
Syndecan-3-mediated signaling events	0.1136	60	2129	35	-0.091	0.041	1000	-1000	0	-1000
Effects of Botulinum toxin	0.1136	60	1564	26	-0.087	0.024	1000	-1000	-0.002	-1000
S1P5 pathway	0.1117	59	1010	17	-0.047	0.035	1000	-1000	-0.006	-1000
Thromboxane A2 receptor signaling	0.1061	56	5904	105	-0.11	0.039	1000	-1000	-0.032	-1000
Syndecan-2-mediated signaling events	0.1061	56	3929	69	-0.091	0.019	1000	-1000	-0.014	-1000
amb2 Integrin signaling	0.1042	55	4568	82	-0.096	0.025	1000	-1000	-0.022	-1000
ErbB2/ErbB3 signaling events	0.1023	54	3513	65	-0.082	0.025	1000	-1000	-0.021	-1000
Nongenotropic Androgen signaling	0.0966	51	2656	52	-0.1	0.052	1000	-1000	-0.016	-1000
Osteopontin-mediated events	0.0928	49	1894	38	-0.068	0.018	1000	-1000	-0.013	-1000
EPHB forward signaling	0.0928	49	4201	85	-0.04	0.027	1000	-1000	-0.025	-1000
Noncanonical Wnt signaling pathway	0.0909	48	1260	26	-0.033	0.019	1000	-1000	-0.02	-1000
BCR signaling pathway	0.0909	48	4832	99	-0.076	0.029	1000	-1000	-0.026	-1000
S1P3 pathway	0.0890	47	1990	42	-0.065	0.016	1000	-1000	-0.007	-1000
E-cadherin signaling in keratinocytes	0.0871	46	1986	43	-0.08	0.027	1000	-1000	-0.004	-1000
PLK2 and PLK4 events	0.0833	44	132	3	-0.013	0.017	1000	-1000	0.006	-1000
Glypican 1 network	0.0833	44	2135	48	-0.078	0.019	1000	-1000	-0.007	-1000
S1P1 pathway	0.0814	43	1550	36	-0.07	0.015	1000	-1000	-0.025	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0814	43	5490	125	-0.08	0.023	1000	-1000	-0.03	-1000
Signaling events mediated by PTP1B	0.0758	40	3101	76	-0.082	0.045	1000	-1000	-0.022	-1000
TCGA08_rtk_signaling	0.0758	40	1043	26	-0.08	0.028	1000	-1000	-0.014	-1000
IL6-mediated signaling events	0.0758	40	3001	75	-0.084	0.035	1000	-1000	-0.014	-1000
IGF1 pathway	0.0758	40	2314	57	-0.021	0.021	1000	-1000	-0.016	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0739	39	2677	68	-0.12	0.037	1000	-1000	-0.046	-1000
IL2 signaling events mediated by STAT5	0.0739	39	864	22	-0.12	0.022	1000	-1000	-0.004	-1000
TCGA08_retinoblastoma	0.0739	39	316	8	-0.016	0.005	1000	-1000	-0.001	-1000
Reelin signaling pathway	0.0720	38	2177	56	-0.03	0.051	1000	-1000	-0.002	-1000
Class I PI3K signaling events	0.0720	38	2832	73	-0.058	0.038	1000	-1000	-0.012	-1000
Ceramide signaling pathway	0.0701	37	2838	76	-0.045	0.037	1000	-1000	-0.011	-1000
Ras signaling in the CD4+ TCR pathway	0.0701	37	643	17	-0.015	0.016	1000	-1000	-0.004	-1000
Signaling events mediated by HDAC Class III	0.0682	36	1469	40	-0.052	0.038	1000	-1000	-0.015	-1000
IL1-mediated signaling events	0.0682	36	2274	62	-0.034	0.035	1000	-1000	-0.024	-1000
Integrins in angiogenesis	0.0682	36	3042	84	-0.068	0.03	1000	-1000	-0.019	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0682	36	2707	74	-0.08	0.033	1000	-1000	-0.022	-1000
Ephrin B reverse signaling	0.0663	35	1684	48	-0.077	0.032	1000	-1000	-0.022	-1000
Aurora B signaling	0.0663	35	2362	67	-0.052	0.028	1000	-1000	-0.012	-1000
PLK1 signaling events	0.0644	34	2942	85	-0.064	0.024	1000	-1000	-0.016	-1000
mTOR signaling pathway	0.0625	33	1790	53	-0.042	0.026	1000	-1000	-0.021	-1000
IL2 signaling events mediated by PI3K	0.0625	33	1926	58	-0.068	0.035	1000	-1000	-0.012	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0625	33	4078	120	-0.066	0.048	1000	-1000	-0.025	-1000
FoxO family signaling	0.0606	32	2089	64	-0.16	0.022	1000	-1000	-0.018	-1000
Regulation of nuclear SMAD2/3 signaling	0.0587	31	4324	136	-0.28	0.28	1000	-1000	-0.024	-1000
Aurora A signaling	0.0587	31	1892	60	-0.03	0.027	1000	-1000	-0.001	-1000
IFN-gamma pathway	0.0587	31	2130	68	-0.047	0.039	1000	-1000	-0.029	-1000
Signaling events mediated by PRL	0.0587	31	1057	34	-0.037	0.022	1000	-1000	-0.002	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0568	30	843	28	-0.047	0.024	1000	-1000	0	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0568	30	1656	54	-0.022	0.021	1000	-1000	-0.001	-1000
IL4-mediated signaling events	0.0568	30	2805	91	-0.39	0.091	1000	-1000	-0.1	-1000
Presenilin action in Notch and Wnt signaling	0.0530	28	1729	61	-0.12	0.04	1000	-1000	-0.028	-1000
Arf6 downstream pathway	0.0530	28	1212	43	-0.031	0.021	1000	-1000	-0.013	-1000
Plasma membrane estrogen receptor signaling	0.0530	28	2460	86	-0.083	0.035	1000	-1000	-0.027	-1000
VEGFR1 specific signals	0.0530	28	1615	56	-0.071	0.031	1000	-1000	0	-1000
p75(NTR)-mediated signaling	0.0511	27	3478	125	-0.1	0.041	1000	-1000	-0.022	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0511	27	1001	37	-0.078	0.047	1000	-1000	-0.002	-1000
BMP receptor signaling	0.0492	26	2111	81	-0.051	0.048	1000	-1000	-0.035	-1000
EPO signaling pathway	0.0492	26	1431	55	-0.017	0.044	1000	-1000	-0.002	-1000
Paxillin-dependent events mediated by a4b1	0.0492	26	943	36	-0.078	0.048	1000	-1000	-0.021	-1000
Regulation of p38-alpha and p38-beta	0.0492	26	1445	54	-0.04	0.034	1000	-1000	-0.002	-1000
E-cadherin signaling in the nascent adherens junction	0.0492	26	2042	76	-0.031	0.04	1000	-1000	-0.025	-1000
Regulation of Telomerase	0.0492	26	2676	102	-0.08	0.036	1000	-1000	-0.032	-1000
p38 MAPK signaling pathway	0.0492	26	1171	44	-0.047	0.022	1000	-1000	-0.025	-1000
FAS signaling pathway (CD95)	0.0473	25	1185	47	-0.028	0.024	1000	-1000	-0.023	-1000
PDGFR-beta signaling pathway	0.0473	25	2485	97	-0.074	0.035	1000	-1000	-0.026	-1000
Arf6 signaling events	0.0455	24	1497	62	-0.08	0.048	1000	-1000	-0.001	-1000
Canonical Wnt signaling pathway	0.0455	24	1262	51	-0.14	0.079	1000	-1000	-0.022	-1000
IL23-mediated signaling events	0.0455	24	1477	60	-0.21	0.03	1000	-1000	-0.026	-1000
BARD1 signaling events	0.0436	23	1344	57	-0.02	0.036	1000	-1000	-0.026	-1000
Hedgehog signaling events mediated by Gli proteins	0.0436	23	1496	65	-0.046	0.04	1000	-1000	-0.015	-1000
Signaling mediated by p38-gamma and p38-delta	0.0436	23	346	15	-0.019	0.022	1000	-1000	0	-1000
ErbB4 signaling events	0.0417	22	1547	69	-0.084	0.034	1000	-1000	-0.008	-1000
Class I PI3K signaling events mediated by Akt	0.0417	22	1534	68	-0.014	0.038	1000	-1000	-0.008	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0417	22	1770	78	-0.019	0.035	1000	-1000	-0.025	-1000
Coregulation of Androgen receptor activity	0.0398	21	1616	76	-0.045	0.038	1000	-1000	-0.01	-1000
Glucocorticoid receptor regulatory network	0.0398	21	2399	114	-0.21	0.062	1000	-1000	-0.039	-1000
TRAIL signaling pathway	0.0398	21	1030	48	-0.014	0.033	1000	-1000	-0.01	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0398	21	984	45	-0.028	0.027	1000	-1000	-0.025	-1000
Insulin Pathway	0.0398	21	1568	74	-0.031	0.04	1000	-1000	-0.023	-1000
E-cadherin signaling events	0.0398	21	109	5	0.007	0.027	1000	-1000	0.007	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0379	20	471	23	-0.011	0.024	1000	-1000	-0.003	-1000
Circadian rhythm pathway	0.0379	20	450	22	-0.014	0.019	1000	-1000	-0.012	-1000
Calcium signaling in the CD4+ TCR pathway	0.0379	20	627	31	-0.042	0.083	1000	-1000	-0.046	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0360	19	1619	85	-0.12	0.031	1000	-1000	-0.02	-1000
Retinoic acid receptors-mediated signaling	0.0360	19	1127	58	-0.051	0.045	1000	-1000	-0.013	-1000
JNK signaling in the CD4+ TCR pathway	0.0341	18	318	17	-0.012	0.028	1000	-1000	-0.006	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0341	18	608	33	-0.019	0.038	1000	-1000	-0.002	-1000
IL12-mediated signaling events	0.0322	17	1540	87	-0.17	0.04	1000	-1000	-0.076	-1000
Insulin-mediated glucose transport	0.0322	17	549	32	-0.006	0.019	1000	-1000	-0.002	-1000
Signaling events mediated by HDAC Class I	0.0322	17	1798	104	-0.025	0.031	1000	-1000	-0.015	-1000
Visual signal transduction: Cones	0.0303	16	622	38	-0.066	0.042	1000	-1000	0	-1000
TCGA08_p53	0.0303	16	116	7	-0.021	0.013	1000	-1000	-0.001	-1000
Atypical NF-kappaB pathway	0.0303	16	507	31	-0.015	0.028	1000	-1000	-0.002	-1000
Signaling events mediated by HDAC Class II	0.0284	15	1199	75	-0.017	0.044	1000	-1000	-0.015	-1000
Cellular roles of Anthrax toxin	0.0284	15	593	39	-0.086	0.018	1000	-1000	-0.008	-1000
Signaling events regulated by Ret tyrosine kinase	0.0284	15	1281	82	-0.032	0.047	1000	-1000	-0.031	-1000
ceramide signaling pathway	0.0284	15	783	49	-0.01	0.024	1000	-1000	-0.003	-1000
FOXA2 and FOXA3 transcription factor networks	0.0265	14	668	46	-0.021	0.15	1000	-1000	-0.019	-1000
Nectin adhesion pathway	0.0265	14	933	63	-0.015	0.046	1000	-1000	-0.031	-1000
TCR signaling in naïve CD8+ T cells	0.0265	14	1363	93	-0.031	0.039	1000	-1000	-0.025	-1000
Arf6 trafficking events	0.0265	14	1010	71	-0.028	0.03	1000	-1000	-0.012	-1000
Caspase cascade in apoptosis	0.0246	13	984	74	-0.056	0.031	1000	-1000	-0.018	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0246	13	1113	83	-0.035	0.05	1000	-1000	-0.005	-1000
IL27-mediated signaling events	0.0227	12	648	51	-0.009	0.026	1000	-1000	-0.022	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0227	12	334	27	-0.01	0.036	1000	-1000	-0.018	-1000
Regulation of Androgen receptor activity	0.0227	12	892	70	-0.032	0.064	1000	-1000	-0.019	-1000
Canonical NF-kappaB pathway	0.0208	11	451	39	-0.01	0.061	1000	-1000	-0.002	-1000
Signaling mediated by p38-alpha and p38-beta	0.0208	11	526	44	-0.001	0.03	1000	-1000	-0.003	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0189	10	558	52	-0.029	0.057	1000	-1000	-0.008	-1000
Signaling events mediated by the Hedgehog family	0.0170	9	499	52	-0.015	0.053	1000	-1000	-0.011	-1000
Aurora C signaling	0.0170	9	66	7	0	0.03	1000	-1000	-0.004	-1000
Arf1 pathway	0.0152	8	463	54	-0.003	0.028	1000	-1000	-0.003	-1000
LPA4-mediated signaling events	0.0133	7	89	12	0	0.015	1000	-1000	0	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0133	7	254	34	-0.028	0.047	1000	-1000	-0.012	-1000
Alternative NF-kappaB pathway	0.0114	6	87	13	0	0.048	1000	-1000	0	-1000
Rapid glucocorticoid signaling	0.0076	4	91	20	0	0.018	1000	-1000	0	-1000
a4b1 and a4b7 Integrin signaling	0.0057	3	17	5	0.016	0.026	1000	-1000	0.007	-1000
Visual signal transduction: Rods	0.0038	2	135	52	0	0.043	1000	-1000	-0.001	-1000
Ephrin A reverse signaling	0.0000	0	1	7	0	0.026	1000	-1000	0	-1000
Class IB PI3K non-lipid kinase events	0.0000	0	0	3	-0.019	0.019	1000	-1000	-0.006	-1000
Total	NA	4249	247521	7203	-8.8	4.8	131000	-131000	-2.1	-131000

HIF-1-alpha transcription factor 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
PKM2	-0.32	0.52	-9999	-0.88	201	201
HDAC7	-0.003	0.006	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.22	0.45	-9999	-0.78	165	165
SMAD4	-0.003	0.079	-9999	-0.29	36	36
ID2	-0.32	0.53	-9999	-0.89	199	199
AP1	-0.029	0.11	-9999	-0.24	93	93
ABCG2	-0.34	0.53	-9999	-0.89	209	209
HIF1A	-0.04	0.095	-9999	-0.14	175	175
TFF3	-0.32	0.52	-9999	-0.88	199	199
GATA2	0.019	0.012	-9999	-0.12	1	1
AKT1	-0.043	0.11	-9999	-0.17	143	143
response to hypoxia	-0.043	0.072	-9999	-0.12	175	175
MCL1	-0.32	0.52	-9999	-0.87	200	200
NDRG1	-0.34	0.54	-9999	-0.89	211	211
SERPINE1	-0.35	0.54	-9999	-0.9	214	214
FECH	-0.32	0.52	-9999	-0.87	200	200
FURIN	-0.32	0.52	-9999	-0.87	199	199
NCOA2	0.02	0.01	-9999	-10000	0	0
EP300	-0.038	0.12	-9999	-0.37	32	32
HMOX1	-0.34	0.54	-9999	-0.91	207	207
BHLHE40	-0.32	0.51	-9999	-0.87	200	200
BHLHE41	-0.32	0.51	-9999	-0.87	200	200
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.015	0.13	-9999	-0.21	67	67
ENG	-0.028	0.1	-9999	-0.23	44	44
JUN	-0.001	0.077	-9999	-0.28	37	37
RORA	-0.32	0.52	-9999	-0.88	202	202
ABCB1	-0.16	0.34	-9999	-1.2	45	45
TFRC	-0.33	0.53	-9999	-0.88	203	203
CXCR4	-0.34	0.53	-9999	-0.89	207	207
TF	-0.37	0.53	-9999	-0.88	225	225
CITED2	-0.32	0.52	-9999	-0.89	200	200
HIF1A/ARNT	-0.35	0.7	-9999	-1.1	177	177
LDHA	-0.11	0.32	-9999	-1.2	38	38
ETS1	-0.32	0.52	-9999	-0.88	198	198
PGK1	-0.32	0.53	-9999	-0.88	203	203
NOS2	-0.32	0.51	-9999	-0.87	200	200
ITGB2	-0.34	0.53	-9999	-0.9	203	203
ALDOA	-0.32	0.52	-9999	-0.88	198	198
Cbp/p300/CITED2	-0.32	0.55	-9999	-0.96	183	183
FOS	-0.045	0.12	-9999	-0.22	146	146
HK2	-0.32	0.52	-9999	-0.88	199	199
SP1	0.019	0.021	-9999	-10000	0	0
GCK	-0.047	0.16	-9999	-0.55	13	13
HK1	-0.32	0.52	-9999	-0.88	198	198
NPM1	-0.32	0.52	-9999	-0.88	199	199
EGLN1	-0.32	0.52	-9999	-0.88	201	201
CREB1	0.019	0.038	-9999	-0.27	7	7
PGM1	-0.32	0.52	-9999	-0.87	201	201
SMAD3	0.019	0.006	-9999	-0.11	1	1
EDN1	-0.046	0.16	-9999	-0.61	20	20
IGFBP1	-0.32	0.52	-9999	-0.87	200	200
VEGFA	-0.26	0.4	-9999	-0.7	198	198
HIF1A/JAB1	-0.013	0.074	-9999	-0.19	32	32
CP	-0.35	0.54	-9999	-0.9	208	208
CXCL12	-0.32	0.52	-9999	-0.87	204	204
COPS5	0.017	0.03	-9999	-0.29	5	5
SMAD3/SMAD4	0.013	0.056	-9999	-0.19	36	36
BNIP3	-0.32	0.53	-9999	-0.89	200	200
EGLN3	-0.32	0.52	-9999	-0.86	207	207
CA9	-0.32	0.52	-9999	-0.86	209	209
TERT	-0.32	0.52	-9999	-0.87	199	199
ENO1	-0.32	0.52	-9999	-0.88	200	200
PFKL	-0.32	0.52	-9999	-0.88	198	198
NCOA1	-0.005	0.083	-9999	-0.28	43	43
ADM	-0.35	0.54	-9999	-0.89	215	215
ARNT	-0.033	0.074	-9999	-0.13	123	123
HNF4A	0.022	0.004	-9999	-10000	0	0
ADFP	-0.34	0.54	-9999	-0.9	210	210
SLC2A1	-0.23	0.39	-9999	-0.68	186	186
LEP	-0.32	0.52	-9999	-0.87	199	199
HIF1A/ARNT/Cbp/p300	-0.23	0.46	-9999	-0.78	172	172
EPO	-0.14	0.3	-9999	-0.55	122	122
CREBBP	-0.032	0.11	-9999	-0.33	25	25
HIF1A/ARNT/Cbp/p300/HDAC7	-0.25	0.48	-9999	-0.82	171	171
PFKFB3	-0.33	0.53	-9999	-0.89	204	204
NT5E	-0.34	0.53	-9999	-0.88	213	213

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.038	0.15	-10000	0	-0.48	45	45
Syndecan-4/Syndesmos	-0.17	0.28	-10000	0	-0.47	204	204
positive regulation of JNK cascade	-0.16	0.26	-10000	0	-0.45	205	205
Syndecan-4/ADAM12	-0.16	0.28	-10000	0	-0.46	204	204
CCL5	0.006	0.039	-10000	0	-0.11	52	52
Rac1/GDP	0.011	0.024	-10000	0	-0.2	7	7
DNM2	0.019	0	-10000	0	-10000	0	0
ITGA5	-0.002	0.07	-10000	0	-0.19	53	53
SDCBP	0.011	0.05	-10000	0	-0.29	14	14
PLG	0.022	0.006	-10000	0	-10000	0	0
ADAM12	0.016	0.019	-10000	0	-0.11	11	11
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.002	0.01	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	-0.17	0.28	-10000	0	-0.47	204	204
Syndecan-4/CXCL12/CXCR4	-0.18	0.29	-10000	0	-0.48	205	205
Syndecan-4/Laminin alpha3	-0.16	0.28	-10000	0	-0.46	205	205
MDK	-0.025	0.1	-10000	0	-0.24	89	89
Syndecan-4/FZD7	-0.18	0.3	-10000	0	-0.5	205	205
Syndecan-4/Midkine	-0.18	0.3	-10000	0	-0.49	204	204
FZD7	-0.047	0.12	-10000	0	-0.22	148	148
Syndecan-4/FGFR1/FGF	-0.14	0.27	-10000	0	-0.42	204	204
THBS1	0	0.046	-10000	0	-0.11	79	79
integrin-mediated signaling pathway	-0.17	0.28	-10000	0	-0.47	206	206
positive regulation of MAPKKK cascade	-0.16	0.26	-10000	0	-0.45	205	205
Syndecan-4/TACI	-0.16	0.28	-10000	0	-0.46	204	204
CXCR4	-0.032	0.11	-10000	0	-0.22	111	111
cell adhesion	0.002	0.074	-10000	0	-0.26	33	33
Syndecan-4/Dynamin	-0.16	0.28	-10000	0	-0.46	204	204
Syndecan-4/TSP1	-0.17	0.28	-10000	0	-0.46	205	205
Syndecan-4/GIPC	-0.16	0.28	-10000	0	-0.46	204	204
Syndecan-4/RANTES	-0.17	0.28	-10000	0	-0.46	204	204
ITGB1	0.019	0	-10000	0	-10000	0	0
LAMA1	0	0	-10000	0	-10000	0	0
LAMA3	0.01	0.034	-10000	0	-0.11	38	38
RAC1	0.015	0.035	-10000	0	-0.29	7	7
PRKCA	0.022	0.028	0.12	2	-10000	0	2
Syndecan-4/alpha-Actinin	-0.18	0.3	-10000	0	-0.5	204	204
TFPI	-0.019	0.086	-10000	0	-0.17	105	105
F2	0.007	0.016	-10000	0	-0.13	2	2
alpha5/beta1 Integrin	0.013	0.049	-10000	0	-0.19	24	24
positive regulation of cell adhesion	-0.16	0.27	-10000	0	-0.45	205	205
ACTN1	-0.033	0.11	-10000	0	-0.24	108	108
TNC	-0.041	0.12	-10000	0	-0.25	119	119
Syndecan-4/CXCL12	-0.17	0.28	-10000	0	-0.47	204	204
FGF6	0.019	0	-10000	0	-10000	0	0
RHOA	0.015	0.035	-10000	0	-0.29	7	7
CXCL12	-0.001	0.048	-10000	0	-0.11	78	78
TNFRSF13B	0.019	0.006	-10000	0	-10000	0	0
FGF2	0.013	0.036	-10000	0	-0.16	19	19
FGFR1	0.019	0.008	-10000	0	-0.11	2	2
Syndecan-4/PI-4-5-P2	-0.17	0.28	-10000	0	-0.47	204	204
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.004	0.066	-10000	0	-0.24	34	34
cell migration	-0.003	0.003	-10000	0	-10000	0	0
PRKCD	0.015	0.029	-10000	0	-0.11	27	27
vasculogenesis	-0.16	0.27	-10000	0	-0.44	205	205
SDC4	-0.18	0.3	-10000	0	-0.5	204	204
Syndecan-4/Tenascin C	-0.18	0.3	-10000	0	-0.5	206	206
Syndecan-4/PI-4-5-P2/PKC alpha	-0.003	0.007	-10000	0	-10000	0	0
Syndecan-4/Syntenin	-0.16	0.29	-10000	0	-0.46	205	205
MMP9	-0.1	0.13	-10000	0	-0.21	268	268
Rac1/GTP	0.002	0.076	-10000	0	-0.27	33	33
cytoskeleton organization	-0.16	0.26	-10000	0	-0.45	204	204
GIPC1	0.019	0	-10000	0	-10000	0	0
Syndecan-4/TFPI	-0.18	0.29	-10000	0	-0.48	204	204

×

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	-0.22	0.6	-9999	-1.2	115	115
PLK1	0.014	0.063	-9999	-10000	0	0
BIRC5	-0.15	0.45	-9999	-1.3	64	64
HSPA1B	-0.22	0.6	-9999	-1.2	122	122
MAP2K1	0.013	0.058	-9999	-0.29	8	8
BRCA2	-0.22	0.6	-9999	-1.2	113	113
FOXM1	-0.42	1	-9999	-2	122	122
XRCC1	-0.22	0.6	-9999	-1.2	113	113
FOXM1B/p19	-0.4	0.6	-9999	-1.4	123	123
Cyclin D1/CDK4	-0.22	0.56	-9999	-1.1	126	126
CDC2	-0.26	0.67	-9999	-1.4	117	117
TGFA	-0.18	0.53	-9999	-1	121	121
SKP2	-0.22	0.6	-9999	-1.2	113	113
CCNE1	0.01	0.035	-9999	-0.12	37	37
CKS1B	-0.24	0.62	-9999	-1.3	119	119
RB1	-0.17	0.34	-9999	-0.94	65	65
FOXM1C/SP1	-0.31	0.74	-9999	-1.5	122	122
AURKB	0.012	0.087	-9999	-1.4	1	1
CENPF	-0.26	0.64	-9999	-1.3	128	128
CDK4	-0.008	0.07	-9999	-0.15	80	80
MYC	-0.2	0.54	-9999	-1.1	124	124
CHEK2	0.01	0.057	-9999	-0.14	30	30
ONECUT1	-0.22	0.58	-9999	-1.2	122	122
CDKN2A	-0.021	0.059	-9999	-0.11	141	141
LAMA4	-0.22	0.6	-9999	-1.2	114	114
FOXM1B/HNF6	-0.3	0.74	-9999	-1.5	122	122
FOS	-0.3	0.66	-9999	-1.2	153	153
SP1	0.018	0.009	-9999	-10000	0	0
CDC25B	-0.23	0.61	-9999	-1.3	117	117
response to radiation	0.002	0.034	-9999	-10000	0	0
CENPB	-0.22	0.6	-9999	-1.2	113	113
CENPA	-0.23	0.61	-9999	-1.2	118	118
NEK2	-0.22	0.6	-9999	-1.2	113	113
HIST1H2BA	-0.22	0.6	-9999	-1.2	122	122
CCNA2	-0.027	0.1	-9999	-0.2	117	117
EP300	0.012	0.046	-9999	-0.24	15	15
CCNB1/CDK1	-0.34	0.8	-9999	-1.6	128	128
CCNB2	-0.25	0.64	-9999	-1.3	122	122
CCNB1	-0.27	0.68	-9999	-1.4	129	129
ETV5	-0.26	0.64	-9999	-1.2	136	136
ESR1	-0.22	0.6	-9999	-1.2	114	114
CCND1	-0.22	0.57	-9999	-1.1	126	126
GSK3A	0.018	0.037	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	0.003	0.087	-9999	-0.18	71	71
CDK2	0.011	0.037	-9999	-0.13	29	29
G2/M transition of mitotic cell cycle	0.001	0.041	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.26	0.67	-9999	-1.4	121	121
GAS1	-0.23	0.61	-9999	-1.2	120	120
MMP2	-0.26	0.64	-9999	-1.3	128	128
RB1/FOXM1C	-0.23	0.6	-9999	-1.2	127	127
CREBBP	0.019	0	-9999	-10000	0	0

×

Angiopoietin receptor Tie2-mediated 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.24	0.42	-10000	0	-0.86	146	146
NCK1/PAK1/Dok-R	-0.13	0.18	-10000	0	-0.4	148	148
NCK1/Dok-R	-0.14	0.37	-10000	0	-0.91	99	99
PIK3CA	-0.01	0.085	-10000	0	-0.22	65	65
mol:beta2-estradiol	0.043	0.091	0.23	99	-10000	0	99
RELA	0.018	0.02	-10000	0	-0.23	3	3
SHC1	0.003	0.052	-10000	0	-0.15	48	48
Rac/GDP	0.011	0.024	-10000	0	-0.2	7	7
F2	0.066	0.094	0.26	99	-10000	0	99
TNIP2	0.016	0.031	-10000	0	-0.24	7	7
NF kappa B/RelA	-0.12	0.36	-10000	0	-0.86	99	99
FN1	0.001	0.07	-10000	0	-0.26	34	34
PLD2	-0.15	0.38	-10000	0	-0.94	99	99
PTPN11	0.015	0.033	-10000	0	-0.26	7	7
GRB14	0.001	0.047	-10000	0	-0.29	2	2
ELK1	-0.13	0.35	-10000	0	-0.86	99	99
GRB7	0.016	0.019	-10000	0	-0.11	11	11
PAK1	0.017	0.017	-10000	0	-0.11	9	9
Tie2/Ang1/alpha5/beta1 Integrin	-0.14	0.38	-10000	0	-0.91	99	99
CDKN1A	-0.2	0.36	-10000	0	-0.74	141	141
ITGA5	-0.002	0.07	-10000	0	-0.19	53	53
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.15	0.37	-10000	0	-0.91	99	99
CRK	0.009	0.053	-10000	0	-0.28	17	17
mol:NO	-0.17	0.31	-10000	0	-0.62	152	152
PLG	-0.15	0.38	-10000	0	-0.94	99	99
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.2	0.38	-10000	0	-0.81	129	129
GRB2	0.014	0.039	-10000	0	-0.26	10	10
PIK3R1	-0.016	0.095	-10000	0	-0.27	62	62
ANGPT2	-0.27	0.47	-10000	0	-1.1	123	123
BMX	-0.15	0.38	-10000	0	-0.94	99	99
ANGPT1	-0.21	0.45	-10000	0	-1.1	99	99
tube development	-0.22	0.37	-10000	0	-0.71	177	177
ANGPT4	0.016	0.007	-10000	0	-10000	0	0
response to hypoxia	-0.012	0.026	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.16	0.39	-10000	0	-0.97	99	99
alpha5/beta1 Integrin	0.013	0.049	-10000	0	-0.19	24	24
FGF2	0.015	0.036	-10000	0	-0.16	17	17
STAT5A (dimer)	-0.25	0.44	-10000	0	-0.82	184	184
mol:L-citrulline	-0.17	0.31	-10000	0	-0.62	152	152
AGTR1	0.01	0.025	-10000	0	-0.12	13	13
MAPK14	-0.17	0.39	-10000	0	-0.95	99	99
Tie2/SHP2	-0.019	0.13	-10000	0	-0.79	6	6
TEK	-0.028	0.14	-10000	0	-1.1	4	4
RPS6KB1	-0.21	0.38	-10000	0	-0.8	141	141
Angiotensin II/AT1	0.004	0.026	-10000	0	-0.11	6	6
Tie2/Ang1/GRB2	-0.15	0.39	-10000	0	-0.96	99	99
MAPK3	-0.14	0.36	-10000	0	-0.88	99	99
MAPK1	-0.14	0.36	-10000	0	-0.88	99	99
Tie2/Ang1/GRB7	-0.15	0.39	-10000	0	-0.96	99	99
NFKB1	0.014	0.038	-10000	0	-0.22	12	12
MAPK8	-0.15	0.38	-10000	0	-0.94	99	99
PI3K	-0.26	0.46	-10000	0	-0.97	134	134
FES	-0.17	0.38	-10000	0	-0.94	99	99
Crk/Dok-R	-0.15	0.37	-10000	0	-0.91	99	99
Tie2/Ang1/ABIN2	-0.15	0.39	-10000	0	-0.96	99	99
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.21	0.37	-10000	0	-0.76	151	151
STAT5A	0.018	0.008	-10000	0	-0.11	2	2
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.22	0.38	-10000	0	-0.8	141	141
Tie2/Ang2	-0.31	0.52	-10000	0	-0.99	176	176
Tie2/Ang1	-0.16	0.4	-10000	0	-1	99	99
FOXO1	-0.24	0.41	-10000	0	-0.79	177	177
ELF1	0.017	0.046	-10000	0	-0.25	14	14
ELF2	-0.15	0.38	-10000	0	-0.92	99	99
mol:Choline	-0.14	0.37	-10000	0	-0.91	99	99
cell migration	-0.072	0.098	-10000	0	-0.22	150	150
FYN	-0.25	0.42	-10000	0	-0.82	177	177
DOK2	0	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.18	0.32	-10000	0	-0.65	144	144
ETS1	-0.024	0.093	-10000	0	-0.21	99	99
PXN	-0.17	0.32	-10000	0	-0.66	145	145
ITGB1	0.019	0	-10000	0	-10000	0	0
NOS3	-0.2	0.35	-10000	0	-0.71	151	151
RAC1	0.015	0.035	-10000	0	-0.29	7	7
TNF	-0.027	0.096	-10000	0	-0.22	99	99
MAPKKK cascade	-0.14	0.37	-10000	0	-0.91	99	99
RASA1	0.003	0.069	-10000	0	-0.28	29	29
Tie2/Ang1/Shc	-0.16	0.39	-10000	0	-0.97	99	99
NCK1	0.014	0.036	-10000	0	-0.19	14	14
vasculogenesis	-0.15	0.28	-10000	0	-0.55	156	156
mol:Phosphatidic acid	-0.14	0.37	-10000	0	-0.91	99	99
mol:Angiotensin II	-0.005	0.012	-10000	0	-10000	0	0
mol:NADP	-0.17	0.31	-10000	0	-0.62	152	152
Rac1/GTP	-0.2	0.36	-10000	0	-0.74	144	144
MMP2	-0.16	0.39	-10000	0	-0.97	99	99

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.078	0.14	-9999	-0.29	136	136
PTK2B	0.018	0.013	-9999	-0.11	5	5
mol:Ca2+	-0.023	0.16	-9999	-0.56	30	30
EDN1	-0.04	0.086	-9999	-0.18	110	110
EDN3	0.015	0.022	-9999	-0.11	15	15
EDN2	0.018	0.01	-9999	-0.11	3	3
HRAS/GDP	-0.047	0.15	-9999	-0.33	84	84
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.034	0.11	-9999	-0.26	75	75
ADCY4	-0.062	0.11	-9999	-0.25	106	106
ADCY5	-0.062	0.11	-9999	-0.25	106	106
ADCY6	-0.054	0.11	-9999	-0.25	103	103
ADCY7	-0.058	0.12	-9999	-0.25	110	110
ADCY1	-0.054	0.11	-9999	-0.26	97	97
ADCY2	-0.054	0.11	-9999	-0.25	102	102
ADCY3	-0.062	0.11	-9999	-0.25	106	106
ADCY8	-0.06	0.11	-9999	-0.25	111	111
ADCY9	-0.055	0.11	-9999	-0.24	107	107
arachidonic acid secretion	-0.095	0.24	-9999	-0.49	113	113
ETB receptor/Endothelin-1/Gq/GTP	-0.043	0.11	-9999	-0.22	112	112
GNAO1	-0.014	0.085	-9999	-0.2	81	81
HRAS	0.008	0.055	-9999	-0.28	18	18
ETA receptor/Endothelin-1/G12/GTP	-0.066	0.15	-9999	-0.3	116	116
ETA receptor/Endothelin-1/Gs/GTP	-0.052	0.13	-9999	-0.27	97	97
mol:GTP	0	0.005	-9999	-10000	0	0
COL3A1	-0.12	0.2	-9999	-0.44	132	132
EDNRB	-0.062	0.12	-9999	-0.25	140	140
response to oxidative stress	0	0	-9999	-10000	0	0
CYSLTR2	-0.07	0.14	-9999	-0.32	91	91
CYSLTR1	-0.08	0.13	-9999	-0.28	131	131
SLC9A1	-0.042	0.09	-9999	-0.21	84	84
mol:GDP	-0.054	0.15	-9999	-0.34	83	83
SLC9A3	-0.11	0.24	-9999	-0.5	109	109
RAF1	-0.071	0.19	-9999	-0.41	101	101
JUN	-0.056	0.28	-9999	-1.1	34	34
JAK2	-0.075	0.14	-9999	-0.3	108	108
mol:IP3	-0.039	0.11	-9999	-0.27	67	67
ETA receptor/Endothelin-1	-0.087	0.17	-9999	-0.34	129	129
PLCB1	0.014	0.024	-9999	-0.12	17	17
PLCB2	0.018	0.004	-9999	-10000	0	0
ETA receptor/Endothelin-3	-0.038	0.099	-9999	-0.23	79	79
FOS	-0.14	0.34	-9999	-0.89	87	87
Gai/GDP	-0.095	0.29	-9999	-0.82	67	67
CRK	0.009	0.054	-9999	-0.28	17	17
mol:Ca ++	-0.091	0.18	-9999	-0.37	122	122
BCAR1	0	0	-9999	-10000	0	0
PRKCB1	-0.044	0.12	-9999	-0.27	82	82
GNAQ	0.014	0.024	-9999	-0.11	17	17
GNAZ	-0.007	0.082	-9999	-0.24	55	55
GNAL	0.018	0.01	-9999	-0.11	3	3
Gs family/GDP	-0.044	0.14	-9999	-0.32	76	76
ETA receptor/Endothelin-1/Gq/GTP	-0.044	0.13	-9999	-0.29	83	83
MAPK14	-0.028	0.099	-9999	-0.22	76	76
TRPC6	-0.025	0.17	-9999	-0.59	30	30
GNAI2	0	0.073	-9999	-0.28	34	34
GNAI3	0.014	0.038	-9999	-0.29	8	8
GNAI1	-0.047	0.11	-9999	-0.2	158	158
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.033	0.1	-9999	-0.23	81	81
ETB receptor/Endothelin-2	-0.028	0.088	-9999	-0.19	108	108
ETB receptor/Endothelin-3	-0.03	0.089	-9999	-0.19	108	108
ETB receptor/Endothelin-1	-0.069	0.12	-9999	-0.22	175	175
MAPK3	-0.12	0.31	-9999	-0.79	88	88
MAPK1	-0.13	0.33	-9999	-0.81	91	91
Rac1/GDP	-0.045	0.15	-9999	-0.34	76	76
cAMP biosynthetic process	-0.036	0.1	-9999	-0.24	82	82
MAPK8	-0.038	0.19	-9999	-0.65	36	36
SRC	0.019	0	-9999	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.097	0.18	-9999	-0.34	130	130
p130Cas/CRK/Src/PYK2	-0.035	0.16	-9999	-0.46	51	51
mol:K +	0	0	-9999	-10000	0	0
G12/GDP	-0.052	0.16	-9999	-0.34	89	89
COL1A2	-0.16	0.26	-9999	-0.54	139	139
EntrezGene:2778	0	0	-9999	-10000	0	0
ETA receptor/Endothelin-2	-0.037	0.099	-9999	-0.2	109	109
mol:DAG	-0.039	0.11	-9999	-0.28	67	67
MAP2K2	-0.093	0.24	-9999	-0.58	92	92
MAP2K1	-0.095	0.25	-9999	-0.59	93	93
EDNRA	-0.071	0.14	-9999	-0.24	157	157
positive regulation of muscle contraction	-0.063	0.13	-9999	-0.29	102	102
Gq family/GDP	-0.025	0.15	-9999	-0.33	71	71
HRAS/GTP	-0.05	0.14	-9999	-0.32	82	82
PRKCH	-0.037	0.11	-9999	-0.28	66	66
RAC1	0.015	0.035	-9999	-0.29	7	7
PRKCA	-0.036	0.11	-9999	-0.27	66	66
PRKCB	-0.041	0.11	-9999	-0.27	69	69
PRKCE	-0.036	0.11	-9999	-0.27	66	66
PRKCD	-0.039	0.12	-9999	-0.28	69	69
PRKCG	-0.036	0.11	-9999	-0.28	65	65
regulation of vascular smooth muscle contraction	-0.17	0.41	-9999	-1.1	87	87
PRKCQ	-0.038	0.11	-9999	-0.28	67	67
PLA2G4A	-0.11	0.26	-9999	-0.54	113	113
GNA14	0.015	0.023	-9999	-0.11	15	15
GNA15	0.011	0.034	-9999	-0.13	26	26
GNA12	-0.005	0.082	-9999	-0.27	43	43
GNA11	0.003	0.07	-9999	-0.3	27	27
Rac1/GTP	-0.057	0.14	-9999	-0.3	98	98
MMP1	0.042	0.084	-9999	-10000	0	0

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.009	0.055	-9999	-0.28	18	18
EGFR	-0.08	0.12	-9999	-0.18	267	267
EGF/EGFR	-0.041	0.072	-9999	-0.14	144	144
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.023	0.069	-9999	-0.13	110	110
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.028	0.099	-9999	-0.2	116	116
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	0.014	0.025	-9999	-0.11	21	21
EGF/EGFR dimer/SHC	-0.034	0.075	-9999	-0.15	120	120
mol:GDP	-0.024	0.067	-9999	-0.13	110	110
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.007	0.039	-9999	-0.12	47	47
GRB2/SOS1	0.011	0.026	-9999	-0.17	10	10
HRAS/GTP	-0.027	0.064	-9999	-0.12	120	120
SHC1	0.004	0.052	-9999	-0.14	48	48
HRAS/GDP	-0.024	0.069	-9999	-0.13	120	120
FRAP1	-0.024	0.059	-9999	-0.12	110	110
EGF/EGFR dimer	-0.045	0.082	-9999	-0.18	107	107
SOS1	0	0	-9999	-10000	0	0
GRB2	0.014	0.039	-9999	-0.26	10	10
ETA receptor/Endothelin-1	-0.013	0.074	-9999	-0.18	68	68

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.007	0.049	-9999	-0.16	37	37
CCL5	0.006	0.039	-9999	-0.11	52	52
SDCBP	0.011	0.05	-9999	-0.29	14	14
FGFR/FGF2/Syndecan-1	-0.052	0.088	-9999	-0.17	147	147
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.045	0.09	-9999	-0.22	55	55
Syndecan-1/Syntenin	-0.043	0.09	-9999	-0.22	54	54
MAPK3	-0.042	0.092	-9999	-0.23	58	58
HGF/MET	0.018	0.03	-9999	-0.14	4	4
TGFB1/TGF beta receptor Type II	0.007	0.049	-9999	-0.16	37	37
BSG	0.001	0.067	-9999	-0.22	39	39
keratinocyte migration	-0.045	0.089	-9999	-0.22	55	55
Syndecan-1/RANTES	-0.046	0.09	-9999	-0.21	63	63
Syndecan-1/CD147	-0.046	0.099	-9999	-0.23	70	70
Syndecan-1/Syntenin/PIP2	-0.043	0.087	-9999	-0.21	54	54
LAMA5	0.007	0.053	-9999	-0.18	32	32
positive regulation of cell-cell adhesion	-0.043	0.086	-9999	-0.21	54	54
MMP7	-0.014	0.057	-9999	-0.11	134	134
HGF	0.016	0.02	-9999	-0.11	13	13
Syndecan-1/CASK	-0.05	0.083	-9999	-0.16	147	147
Syndecan-1/HGF/MET	-0.037	0.091	-9999	-0.2	59	59
regulation of cell adhesion	-0.042	0.094	-9999	-0.23	61	61
HPSE	0.003	0.054	-9999	-0.15	51	51
positive regulation of cell migration	-0.052	0.088	-9999	-0.17	147	147
SDC1	-0.053	0.089	-9999	-0.17	147	147
Syndecan-1/Collagen	-0.052	0.088	-9999	-0.17	147	147
PPIB	0.004	0.066	-9999	-0.28	27	27
MET	0.007	0.037	-9999	-0.11	47	47
PRKACA	0.019	0	-9999	-10000	0	0
MMP9	-0.096	0.13	-9999	-0.21	270	270
MAPK1	-0.046	0.097	-9999	-0.24	62	62
homophilic cell adhesion	-0.052	0.088	-9999	-0.17	147	147
MMP1	0.002	0.044	-9999	-0.11	70	70

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	-0.005	0.039	-10000	0	-10000	0	0
oxygen homeostasis	-0.008	0.014	-10000	0	-10000	0	0
TCEB2	0.019	0	-10000	0	-10000	0	0
TCEB1	0.014	0.041	-10000	0	-0.27	10	10
VHL/Elongin B/Elongin C/HIF2A	-0.029	0.11	-10000	0	-0.24	60	60
EPO	-0.11	0.25	-10000	0	-0.48	125	125
FIH (dimer)	0.009	0.016	-10000	0	-10000	0	0
APEX1	0.003	0.039	-10000	0	-0.33	5	5
SERPINE1	-0.17	0.3	-10000	0	-0.57	153	153
FLT1	-0.003	0.043	-10000	0	-10000	0	0
ADORA2A	-0.13	0.26	-10000	0	-0.5	131	131
germ cell development	-0.13	0.26	-10000	0	-0.46	158	158
SLC11A2	-0.13	0.27	-10000	0	-0.52	131	131
BHLHE40	-0.14	0.26	-10000	0	-0.48	158	158
HIF1AN	0.009	0.016	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.057	0.16	-10000	0	-0.3	117	117
ETS1	0.029	0.014	-10000	0	-10000	0	0
CITED2	-0.063	0.24	-10000	0	-1.1	27	27
KDR	-0.03	0.17	-10000	0	-1.1	11	11
PGK1	-0.14	0.28	-10000	0	-0.54	135	135
SIRT1	0.008	0.048	-10000	0	-0.16	32	32
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF2A/ARNT	-0.14	0.33	-10000	0	-0.55	156	156
EPAS1	-0.044	0.12	-10000	0	-0.22	107	107
SP1	0.026	0.004	-10000	0	-10000	0	0
ABCG2	-0.16	0.3	-10000	0	-0.55	156	156
EFNA1	-0.14	0.28	-10000	0	-0.54	134	134
FXN	-0.13	0.26	-10000	0	-0.5	131	131
POU5F1	-0.14	0.26	-10000	0	-0.48	158	158
neuron apoptosis	0.13	0.32	0.54	156	-10000	0	156
EP300	0.012	0.046	-10000	0	-0.24	15	15
EGLN3	-0.014	0.068	-10000	0	-0.16	71	71
EGLN2	0.009	0.016	-10000	0	-10000	0	0
EGLN1	0	0.055	-10000	0	-0.25	20	20
VHL/Elongin B/Elongin C	0.023	0.024	-10000	0	-0.16	9	9
VHL	0	0	-10000	0	-10000	0	0
ARNT	0.006	0.022	-10000	0	-0.093	1	1
SLC2A1	-0.14	0.27	-10000	0	-0.52	136	136
TWIST1	-0.17	0.28	-10000	0	-0.5	180	180
ELK1	0.022	0.017	-10000	0	-0.11	1	1
HIF2A/ARNT/Cbp/p300	-0.054	0.16	-10000	0	-0.3	113	113
VEGFA	-0.17	0.3	-10000	0	-0.56	162	162
CREBBP	0.019	0	-10000	0	-10000	0	0

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.033	0.11	-9999	-0.2	134	134
FZD6	-0.02	0.076	-9999	-0.14	128	128
WNT6	0.019	0	-9999	-10000	0	0
WNT4	0.018	0.013	-9999	-0.11	5	5
FZD3	-0.028	0.1	-9999	-0.22	103	103
WNT5A	-0.028	0.1	-9999	-0.24	98	98
WNT11	0.017	0.016	-9999	-0.11	8	8

×

PDGFR-alpha signaling pathway

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.022	0.079	-10000	0	-0.16	100	100
PDGF/PDGFRA/CRKL	-0.017	0.075	-10000	0	-0.19	72	72
positive regulation of JUN kinase activity	-0.01	0.067	-10000	0	-0.15	85	85
CRKL	0.018	0.01	-10000	0	-0.11	3	3
PDGF/PDGFRA/Caveolin-3	-0.017	0.075	-10000	0	-0.19	72	72
AP1	-0.12	0.27	-10000	0	-0.68	92	92
mol:IP3	-0.012	0.061	-10000	0	-0.11	100	100
PLCG1	-0.012	0.061	-10000	0	-0.11	100	100
PDGF/PDGFRA/alphaV Integrin	-0.027	0.091	-10000	0	-0.21	89	89
RAPGEF1	0.019	0	-10000	0	-10000	0	0
CRK	0.009	0.053	-10000	0	-0.28	17	17
mol:Ca2+	-0.012	0.061	-10000	0	-0.11	100	100
CAV3	0.019	0.008	-10000	0	-0.11	2	2
CAV1	-0.071	0.13	-10000	0	-0.22	197	197
SHC/Grb2/SOS1	-0.009	0.068	-10000	0	-0.15	85	85
PDGF/PDGFRA/Shf	-0.03	0.072	-10000	0	-0.18	79	79
FOS	-0.12	0.27	-10000	0	-0.68	91	91
JUN	-0.018	0.069	0.25	10	-0.25	28	38
oligodendrocyte development	-0.027	0.091	-10000	0	-0.21	89	89
GRB2	0.014	0.039	-10000	0	-0.26	10	10
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
mol:DAG	-0.012	0.061	-10000	0	-0.11	100	100
PDGF/PDGFRA	-0.022	0.079	-10000	0	-0.16	100	100
actin cytoskeleton reorganization	-0.018	0.077	-10000	0	-0.19	73	73
SRF	0.02	0.029	-10000	0	-0.18	10	10
SHC1	0.004	0.052	-10000	0	-0.14	48	48
PI3K	-0.036	0.1	-10000	0	-0.19	144	144
PDGF/PDGFRA/Crk/C3G	-0.006	0.073	-10000	0	-0.16	84	84
JAK1	-0.016	0.071	-10000	0	-0.2	49	49
ELK1/SRF	-0.009	0.071	-10000	0	-0.16	79	79
SHB	0.016	0.02	-10000	0	-0.11	13	13
SHF	0	0	-10000	0	-10000	0	0
CSNK2A1	0.02	0.043	-10000	0	-0.27	10	10
GO:0007205	-0.037	0.092	-10000	0	-0.25	71	71
SOS1	0	0	-10000	0	-10000	0	0
Ras protein signal transduction	-0.01	0.067	-10000	0	-0.15	85	85
PDGF/PDGFRA/SHB	-0.018	0.077	-10000	0	-0.19	73	73
PDGF/PDGFRA/Caveolin-1	-0.078	0.12	-10000	0	-0.23	176	176
ITGAV	0.003	0.067	-10000	0	-0.25	32	32
ELK1	-0.033	0.083	-10000	0	-0.2	79	79
PIK3CA	-0.011	0.085	-10000	0	-0.22	65	65
PDGF/PDGFRA/Crk	-0.023	0.084	-10000	0	-0.2	84	84
JAK-STAT cascade	-0.015	0.071	-10000	0	-0.2	49	49
cell proliferation	-0.03	0.072	-10000	0	-0.18	79	79

×

LPA receptor 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.011	0.072	-10000	0	-0.18	68	68
NF kappa B1 p50/RelA/I kappa B alpha	0.007	0.077	-10000	0	-0.21	41	41
AP1	-0.045	0.094	-10000	0	-0.19	125	125
mol:PIP3	-0.061	0.08	-10000	0	-0.16	168	168
AKT1	-0.011	0.094	-10000	0	-0.25	51	51
PTK2B	-0.006	0.056	-10000	0	-0.16	60	60
RHOA	-0.005	0.059	-10000	0	-0.42	7	7
PIK3CB	0.018	0.013	-10000	0	-0.11	5	5
mol:Ca2+	0.007	0.035	-10000	0	-0.13	20	20
MAGI3	0	0	0.001	9	-10000	0	9
RELA	0.018	0.02	-10000	0	-0.23	3	3
apoptosis	-0.014	0.072	-10000	0	-0.2	61	61
HRAS/GDP	0.007	0.037	-10000	0	-0.19	18	18
positive regulation of microtubule depolymerization	-0.024	0.087	-10000	0	-0.17	116	116
NF kappa B1 p50/RelA	-0.022	0.053	-10000	0	-0.15	63	63
endothelial cell migration	-0.038	0.13	-10000	0	-0.4	60	60
ADCY4	-0.055	0.12	-10000	0	-0.27	101	101
ADCY5	-0.055	0.12	-10000	0	-0.27	101	101
ADCY6	-0.05	0.12	-10000	0	-0.27	99	99
ADCY7	-0.054	0.13	-10000	0	-0.28	97	97
ADCY1	-0.05	0.12	-10000	0	-0.27	99	99
ADCY2	-0.05	0.12	-10000	0	-0.27	98	98
ADCY3	-0.055	0.12	-10000	0	-0.27	101	101
ADCY8	-0.053	0.12	-10000	0	-0.27	100	100
ADCY9	-0.05	0.12	-10000	0	-0.27	99	99
GSK3B	-0.008	0.066	-10000	0	-0.16	72	72
arachidonic acid secretion	-0.055	0.14	-10000	0	-0.27	111	111
GNG2	0	0.001	0.001	54	-10000	0	54
TRIP6	-0.031	0.11	-10000	0	-0.29	81	81
GNAO1	-0.021	0.079	-10000	0	-0.2	76	76
HRAS	0.009	0.055	-10000	0	-0.28	18	18
NFKBIA	-0.006	0.075	-10000	0	-0.22	40	40
GAB1	0.003	0.056	-10000	0	-0.15	50	50
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	-0.008	0.2	-10000	0	-0.93	23	23
JUN	-0.002	0.077	-10000	0	-0.28	37	37
LPA/LPA2/NHERF2	0.004	0.026	-10000	0	-0.064	45	45
TIAM1	-0.021	0.23	-10000	0	-1.1	23	23
PIK3R1	-0.015	0.094	-10000	0	-0.27	62	62
mol:IP3	0.007	0.036	-10000	0	-0.14	20	20
PLCB3	0.009	0.023	-10000	0	-10000	0	0
FOS	-0.046	0.12	-10000	0	-0.22	146	146
positive regulation of mitosis	-0.055	0.14	-10000	0	-0.27	111	111
LPA/LPA1-2-3	-0.017	0.056	-10000	0	-0.16	63	63
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0	-10000	0	-0.001	76	76
BCAR1	0	0	-10000	0	-10000	0	0
stress fiber formation	-0.004	0.067	-10000	0	-0.16	68	68
GNAZ	-0.019	0.081	-10000	0	-0.21	72	72
EGFR/PI3K-beta/Gab1	-0.063	0.083	-10000	0	-0.16	168	168
positive regulation of dendritic cell cytokine production	-0.018	0.055	-10000	0	-0.16	63	63
LPA/LPA2/MAGI-3	-0.007	0.023	-10000	0	-0.066	63	63
ARHGEF1	-0.008	0.074	-10000	0	-0.17	81	81
GNAI2	-0.015	0.078	-10000	0	-0.22	60	60
GNAI3	-0.011	0.069	-10000	0	-0.19	60	60
GNAI1	-0.027	0.08	-10000	0	-0.21	73	73
LPA/LPA3	-0.01	0.029	-10000	0	-0.082	65	65
LPA/LPA2	-0.01	0.028	-10000	0	-0.083	63	63
LPA/LPA1	-0.023	0.075	-10000	0	-0.22	60	60
HB-EGF/EGFR	-0.092	0.093	-10000	0	-0.18	260	260
HBEGF	-0.059	0.088	-10000	0	-0.19	152	152
mol:DAG	0.007	0.036	-10000	0	-0.14	20	20
cAMP biosynthetic process	-0.053	0.13	-10000	0	-0.27	105	105
NFKB1	0.014	0.038	-10000	0	-0.22	12	12
SRC	0.019	0	-10000	0	-10000	0	0
GNB1	0.007	0.06	-10000	0	-0.29	21	21
LYN	-0.022	0.096	-10000	0	-0.23	75	75
GNAQ	-0.001	0.026	-10000	0	-0.06	77	77
LPAR2	0	0.001	0.001	6	-0.002	79	85
LPAR3	0	0.001	-10000	0	-0.001	91	91
LPAR1	-0.015	0.045	-10000	0	-0.14	60	60
IL8	-0.2	0.2	-10000	0	-0.42	225	225
PTK2	-0.009	0.062	-10000	0	-0.17	61	61
Rac1/GDP	0.011	0.024	-10000	0	-0.2	7	7
CASP3	-0.015	0.073	-10000	0	-0.2	61	61
EGFR	-0.08	0.12	-10000	0	-0.18	267	267
PLCG1	0.001	0.04	-10000	0	-0.093	62	62
PLD2	-0.007	0.054	-10000	0	-0.15	60	60
G12/G13	-0.008	0.083	-10000	0	-0.18	82	82
PI3K-beta	-0.035	0.081	-10000	0	-0.25	48	48
cell migration	-0.003	0.073	-10000	0	-0.26	29	29
SLC9A3R2	0.019	0	-10000	0	-10000	0	0
PXN	-0.004	0.068	-10000	0	-0.17	68	68
HRAS/GTP	-0.056	0.14	-10000	0	-0.28	111	111
RAC1	0.015	0.035	-10000	0	-0.29	7	7
MMP9	-0.097	0.13	-10000	0	-0.21	270	270
PRKCE	0.019	0	-10000	0	-10000	0	0
PRKCD	0.008	0.036	-10000	0	-0.13	20	20
Gi(beta/gamma)	-0.056	0.14	-10000	0	-0.29	103	103
mol:LPA	-0.016	0.045	-10000	0	-0.14	60	60
TRIP6/p130 Cas/FAK1/Paxillin	-0.021	0.1	-10000	0	-0.24	70	70
MAPKKK cascade	-0.055	0.14	-10000	0	-0.27	111	111
contractile ring contraction involved in cytokinesis	-0.005	0.058	-10000	0	-0.41	7	7
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.001	0.025	-10000	0	-0.06	75	75
GNA15	-0.002	0.029	-10000	0	-0.063	84	84
GNA12	-0.005	0.081	-10000	0	-0.27	43	43
GNA13	0.016	0.021	-10000	0	-0.11	14	14
MAPT	-0.024	0.089	-10000	0	-0.17	114	114
GNA11	-0.006	0.05	-10000	0	-0.12	61	61
Rac1/GTP	-0.01	0.21	-10000	0	-1	23	23
MMP2	-0.039	0.13	-10000	0	-0.4	60	60

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.025	0.1	-9999	-0.24	89	89
GPC2	0	0	-9999	-10000	0	0
GPC2/Midkine	-0.016	0.07	-9999	-0.16	89	89
neuron projection morphogenesis	-0.016	0.07	-9999	-0.16	89	89

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.014	0.085	-9999	-0.2	81	81
CDC42/GTP	-0.034	0.11	-9999	-0.19	143	143
PLCG1	-0.041	0.12	-9999	-0.2	143	143
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0	0.073	-9999	-0.28	34	34
GNAI3	0.014	0.038	-9999	-0.29	8	8
G12/G13	0.009	0.059	-9999	-0.19	39	39
cell migration	-0.034	0.11	-9999	-0.19	143	143
S1PR5	0	0	-9999	-10000	0	0
S1PR4	0	0	-9999	-10000	0	0
MAPK3	-0.04	0.11	-9999	-0.2	143	143
MAPK1	-0.043	0.12	-9999	-0.21	143	143
S1P/S1P5/Gi	-0.047	0.12	-9999	-0.22	143	143
GNAI1	-0.047	0.11	-9999	-0.2	158	158
CDC42/GDP	0.013	0.01	-9999	-0.07	8	8
S1P/S1P5/G12	0	0.046	-9999	-0.16	39	39
RHOA	0.008	0.043	-9999	-0.14	39	39
S1P/S1P4/Gi	-0.047	0.12	-9999	-0.22	143	143
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.007	0.082	-9999	-0.24	55	55
S1P/S1P4/G12/G13	0.01	0.044	-9999	-0.14	39	39
GNA12	-0.005	0.082	-9999	-0.27	43	43
GNA13	0.016	0.021	-9999	-0.11	14	14
CDC42	0.017	0.016	-9999	-0.11	8	8

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	-0.013	0.093	-9999	-0.27	60	60
LAT2	-0.027	0.13	-9999	-0.3	83	83
AP1	-0.035	0.16	-9999	-0.36	79	79
mol:PIP3	-0.019	0.14	-9999	-0.3	85	85
IKBKB	-0.006	0.084	-9999	-0.18	84	84
AKT1	-0.034	0.13	-9999	-0.29	82	82
IKBKG	-0.006	0.084	-9999	-0.18	84	84
MS4A2	0.021	0.006	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	-0.011	0.085	-9999	-0.22	65	65
MAP3K1	-0.022	0.13	-9999	-0.31	68	68
mol:Ca2+	-0.011	0.11	-9999	-0.23	86	86
LYN	-0.019	0.1	-9999	-0.26	72	72
CBLB	-0.027	0.13	-9999	-0.29	83	83
SHC1	0.004	0.052	-9999	-0.14	48	48
RasGAP/p62DOK	0.014	0.054	-9999	-0.15	39	39
positive regulation of cell migration	-0.001	0.045	-9999	-0.15	39	39
INPP5D	0	0	-9999	-10000	0	0
PLD2	-0.012	0.07	-9999	-0.14	104	104
PTPN13	-0.052	0.2	-9999	-0.52	63	63
PTPN11	0.013	0.036	-9999	-0.28	7	7
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.026	0.13	-9999	-0.28	81	81
SYK	-0.005	0.075	-9999	-0.19	62	62
GRB2	0.014	0.039	-9999	-0.26	10	10
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.051	0.12	-9999	-0.3	86	86
LAT	-0.028	0.13	-9999	-0.3	83	83
PAK2	-0.029	0.14	-9999	-0.3	87	87
NFATC2	-0.01	0.019	-9999	-10000	0	0
HRAS	-0.034	0.15	-9999	-0.33	87	87
GAB2	-0.005	0.082	-9999	-0.27	44	44
PLA2G1B	-0.003	0.18	-9999	-0.95	18	18
Fc epsilon R1	0.001	0.067	-9999	-0.14	84	84
Antigen/IgE/Fc epsilon R1	0.003	0.059	-9999	-0.12	84	84
mol:GDP	-0.034	0.15	-9999	-0.34	86	86
JUN	-0.002	0.077	-9999	-0.28	37	37
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	-0.015	0.095	-9999	-0.27	62	62
FOS	-0.046	0.12	-9999	-0.22	146	146
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.032	0.14	-9999	-0.31	83	83
CHUK	-0.007	0.084	-9999	-0.18	84	84
KLRG1	-0.019	0.12	-9999	-0.29	70	70
VAV1	-0.03	0.13	-9999	-0.3	84	84
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.027	0.13	-9999	-0.29	83	83
negative regulation of mast cell degranulation	-0.024	0.11	-9999	-0.29	61	61
BTK	-0.034	0.15	-9999	-0.34	82	82
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.05	0.11	-9999	-0.2	151	151
GAB2/PI3K/SHP2	-0.058	0.11	-9999	-0.27	89	89
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.032	0.14	-9999	-0.34	69	69
RAF1	-0.011	0.19	-9999	-1	18	18
Fc epsilon R1/FcgammaRIIB/SHIP	-0.036	0.094	-9999	-0.17	145	145
FCER1G	-0.023	0.098	-9999	-0.23	86	86
FCER1A	0.013	0.027	-9999	-0.11	12	12
Antigen/IgE/Fc epsilon R1/Fyn	-0.006	0.081	-9999	-0.14	125	125
MAPK3	-0.003	0.18	-9999	-0.94	18	18
MAPK1	-0.007	0.19	-9999	-0.99	18	18
NFKB1	0.014	0.038	-9999	-0.22	12	12
MAPK8	0.015	0.076	-9999	-0.61	5	5
DUSP1	-0.005	0.065	-9999	-0.15	74	74
NF-kappa-B/RelA	0.001	0.056	-9999	-0.12	66	66
actin cytoskeleton reorganization	-0.047	0.19	-9999	-0.52	60	60
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.039	0.16	-9999	-0.36	78	78
FER	-0.028	0.13	-9999	-0.29	83	83
RELA	0.018	0.02	-9999	-0.23	3	3
ITK	0.002	0.033	-9999	-0.11	21	21
SOS1	0	0	-9999	-10000	0	0
PLCG1	-0.029	0.15	-9999	-0.33	86	86
cytokine secretion	-0.013	0.033	-9999	-0.1	45	45
SPHK1	-0.031	0.13	-9999	-0.29	85	85
PTK2	-0.05	0.2	-9999	-0.55	60	60
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.052	0.13	-9999	-0.31	86	86
EDG1	-0.001	0.045	-9999	-0.15	39	39
mol:DAG	-0.032	0.15	-9999	-0.32	94	94
MAP2K2	-0.007	0.18	-9999	-0.95	18	18
MAP2K1	-0.009	0.18	-9999	-0.96	18	18
MAP2K7	0.019	0	-9999	-10000	0	0
KLRG1/SHP2	-0.016	0.11	-9999	-0.29	56	56
MAP2K4	0.016	0.098	-9999	-0.98	5	5
Fc epsilon R1/FcgammaRIIB	-0.039	0.1	-9999	-0.18	145	145
mol:Choline	-0.012	0.069	-9999	-0.14	104	104
SHC/Grb2/SOS1	-0.02	0.13	-9999	-0.29	84	84
FYN	-0.019	0.1	-9999	-0.28	68	68
DOK1	0.019	0	-9999	-10000	0	0
PXN	-0.041	0.19	-9999	-0.5	60	60
HCLS1	-0.047	0.16	-9999	-0.35	95	95
PRKCB	-0.017	0.11	-9999	-0.24	87	87
FCGR2B	-0.076	0.12	-9999	-0.2	230	230
IGHE	-0.001	0.004	-9999	-10000	0	0
KLRG1/SHIP	-0.024	0.11	-9999	-0.3	61	61
LCP2	-0.012	0.086	-9999	-0.22	70	70
PLA2G4A	-0.044	0.15	-9999	-0.32	96	96
RASA1	0.003	0.069	-9999	-0.28	29	29
mol:Phosphatidic acid	-0.012	0.069	-9999	-0.14	104	104
IKK complex	0.004	0.067	-9999	-0.15	66	66
WIPF1	0.013	0.038	-9999	-0.18	17	17

×

Syndecan-3-mediated signaling events

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
CTTN	0.018	0.017	-9999	-0.16	4	4
Syndecan-3/Src/Cortactin	-0.045	0.21	-9999	-0.52	79	79
Syndecan-3/Neurocan	-0.076	0.22	-9999	-0.6	77	77
POMC	0.018	0.013	-9999	-0.11	5	5
EGFR	-0.08	0.12	-9999	-0.18	267	267
Syndecan-3/EGFR	-0.084	0.2	-9999	-0.52	85	85
AGRP	0.019	0	-9999	-10000	0	0
NCSTN	0.008	0.055	-9999	-0.26	20	20
PSENEN	0.014	0.041	-9999	-0.27	10	10
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.018	0.02	-9999	-0.29	2	2
APH1A	0.015	0.036	-9999	-0.27	8	8
NCAN	-0.074	0.13	-9999	-0.24	185	185
long-term memory	-0.055	0.21	-9999	-0.54	79	79
Syndecan-3/IL8	-0.08	0.2	-9999	-0.46	98	98
PSEN1	0.011	0.047	-9999	-0.26	15	15
Src/Cortactin	0.027	0.012	-9999	-0.19	1	1
FYN	-0.019	0.1	-9999	-0.28	68	68
limb bud formation	-0.065	0.19	-9999	-0.52	76	76
MC4R	0.019	0.006	-9999	-0.11	1	1
SRC	0.019	0	-9999	-10000	0	0
PTN	-0.015	0.097	-9999	-0.29	58	58
FGFR/FGF/Syndecan-3	-0.066	0.19	-9999	-0.53	76	76
neuron projection morphogenesis	-0.072	0.23	-9999	-0.57	84	84
Syndecan-3/AgRP	-0.053	0.19	-9999	-0.5	76	76
Syndecan-3/AgRP/MC4R	-0.041	0.18	-9999	-0.48	76	76
Fyn/Cortactin	0.001	0.073	-9999	-0.2	63	63
SDC3	-0.066	0.2	-9999	-0.54	76	76
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.079	0.2	-9999	-0.46	98	98
IL8	-0.091	0.13	-9999	-0.21	254	254
Syndecan-3/Fyn/Cortactin	-0.057	0.21	-9999	-0.55	79	79
Syndecan-3/CASK	-0.064	0.18	-9999	-0.51	76	76
alpha-MSH/MC4R	0.027	0.01	-9999	-10000	0	0
Gamma Secretase	0.041	0.063	-9999	-0.17	33	33

×

Effects of Botulinum toxin

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
STX1A	0.007	0.016	-9999	-0.07	22	22
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	0.016	0.047	-9999	-0.19	24	24
STXBP1	-0.02	0.093	-9999	-0.21	91	91
ACh/CHRNA1	-0.009	0.038	-9999	-0.066	149	149
RAB3GAP2/RIMS1/UNC13B	0.024	0.052	-9999	-0.17	32	32
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	0.018	0.011	-9999	-0.11	4	4
mol:ACh	-0.026	0.045	-9999	-0.095	140	140
RAB3GAP2	0.012	0.045	-9999	-0.26	13	13
STX1A/SNAP25/VAMP2	-0.027	0.091	-9999	-0.22	61	61
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.009	0.038	-9999	-0.066	149	149
UNC13B	0.002	0.066	-9999	-0.24	34	34
CHRNA1	0.015	0.022	-9999	-0.11	16	16
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.054	0.083	-9999	-0.11	287	287
SNAP25	-0.061	0.092	-9999	-0.22	134	134
VAMP2	0.001	0.026	-9999	-0.2	8	8
SYT1	-0.087	0.12	-9999	-0.18	274	274
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.003	0.056	-9999	-0.14	65	65
STX1A/SNAP25 fragment 1/VAMP2	-0.027	0.091	-9999	-0.22	61	61

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.035	0.11	0.19	144	-10000	0	144
GNAI2	0	0.073	-10000	0	-0.28	34	34
S1P/S1P5/G12	0	0.046	-10000	0	-0.15	43	43
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.014	0.085	-10000	0	-0.2	81	81
RhoA/GTP	-0.035	0.12	-10000	0	-0.2	144	144
negative regulation of cAMP metabolic process	-0.046	0.12	-10000	0	-0.21	143	143
GNAZ	-0.007	0.082	-10000	0	-0.24	55	55
GNAI3	0.014	0.038	-10000	0	-0.29	8	8
GNA12	-0.005	0.082	-10000	0	-0.27	43	43
S1PR5	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.047	0.12	-10000	0	-0.22	143	143
RhoA/GDP	0.011	0.024	-10000	0	-0.2	7	7
RHOA	0.015	0.035	-10000	0	-0.29	7	7
GNAI1	-0.047	0.11	-10000	0	-0.2	158	158

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.016	0.019	-10000	0	-0.11	11	11
GNB1/GNG2	-0.047	0.074	-10000	0	-0.17	139	139
AKT1	-0.027	0.12	-10000	0	-0.2	156	156
EGF	0.014	0.025	-10000	0	-0.11	21	21
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.024	0.035	-10000	0	-0.18	4	4
mol:Ca2+	-0.036	0.15	-10000	0	-0.28	139	139
LYN	0.022	0.039	-10000	0	-0.19	9	9
RhoA/GTP	-0.03	0.057	-10000	0	-0.12	139	139
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.05	0.17	-10000	0	-0.32	139	139
GNG2	0	0	-10000	0	-10000	0	0
ARRB2	0.013	0.039	-10000	0	-0.2	15	15
TP alpha/Gq family/GDP/G beta5/gamma2	0.015	0.067	-10000	0	-0.25	30	30
G beta5/gamma2	-0.06	0.095	-10000	0	-0.22	139	139
PRKCH	-0.048	0.17	-10000	0	-0.32	139	139
DNM1	0.017	0.017	-10000	0	-0.11	9	9
TXA2/TP beta/beta Arrestin3	0.017	0.015	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-0.002	139	139
PTGDR	0.019	0	-10000	0	-10000	0	0
G12 family/GTP	-0.08	0.13	-10000	0	-0.29	139	139
ADRBK1	0.018	0.014	-10000	0	-0.11	6	6
ADRBK2	0.019	0.006	-10000	0	-0.11	1	1
RhoA/GTP/ROCK1	0.021	0.029	-10000	0	-0.17	11	11
mol:GDP	0.003	0.086	0.15	7	-10000	0	7
mol:NADP	0.019	0.006	-10000	0	-0.11	1	1
RAB11A	0.016	0.033	-10000	0	-0.29	6	6
PRKG1	0.019	0	-10000	0	-10000	0	0
mol:IP3	-0.05	0.18	-10000	0	-0.34	139	139
cell morphogenesis	0.021	0.029	-10000	0	-0.17	11	11
PLCB2	-0.077	0.23	-10000	0	-0.45	139	139
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	0.028	0.03	-10000	0	-0.12	1	1
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.017	0.044	-10000	0	-0.19	14	14
RHOA	0.015	0.035	-10000	0	-0.29	7	7
PTGIR	0.019	0	-10000	0	-10000	0	0
PRKCB1	-0.056	0.18	-10000	0	-0.35	139	139
GNAQ	0.015	0.023	-10000	0	-0.11	17	17
mol:L-citrulline	0.019	0.006	-10000	0	-0.11	1	1
TXA2/TXA2-R family	-0.084	0.24	-10000	0	-0.48	139	139
LCK	0.028	0.03	-10000	0	-0.12	2	2
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.037	0.015	-10000	0	-10000	0	0
TXA2-R family/G12 family/GDP/G beta/gamma	-0.018	0.16	-10000	0	-0.51	47	47
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.034	0.022	-10000	0	-10000	0	0
MAPK14	-0.026	0.12	-10000	0	-0.22	139	139
TGM2/GTP	-0.055	0.2	-10000	0	-0.37	139	139
MAPK11	-0.026	0.12	-10000	0	-0.22	139	139
ARHGEF1	-0.018	0.094	-10000	0	-0.17	139	139
GNAI2	0	0.073	-10000	0	-0.28	34	34
JNK cascade	-0.055	0.19	-10000	0	-0.36	139	139
RAB11/GDP	0.015	0.032	-10000	0	-0.29	6	6
ICAM1	-0.039	0.14	-10000	0	-0.27	139	139
cAMP biosynthetic process	-0.046	0.16	-10000	0	-0.31	139	139
Gq family/GTP/EBP50	0.009	0.051	-10000	0	-0.17	34	34
actin cytoskeleton reorganization	0.021	0.029	-10000	0	-0.17	11	11
SRC	0.028	0.029	-10000	0	-10000	0	0
GNB5	0.017	0.019	-10000	0	-0.14	7	7
GNB1	0.007	0.061	-10000	0	-0.29	21	21
EGF/EGFR	-0.019	0.095	-10000	0	-0.2	83	83
VCAM1	-0.064	0.18	-10000	0	-0.36	139	139
TP beta/Gq family/GDP/G beta5/gamma2	0.015	0.067	-10000	0	-0.25	30	30
platelet activation	-0.034	0.16	-10000	0	-0.28	139	139
PGI2/IP	0.014	0.001	-10000	0	-10000	0	0
PRKACA	0.022	0.002	-10000	0	-10000	0	0
Gq family/GDP/G beta5/gamma2	0.015	0.061	-10000	0	-0.23	30	30
TXA2/TP beta/beta Arrestin2	0.015	0.029	-10000	0	-0.19	6	6
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.024	0.002	-10000	0	-10000	0	0
mol:DAG	-0.061	0.2	-10000	0	-0.38	139	139
EGFR	-0.08	0.12	-10000	0	-0.18	267	267
TXA2/TP alpha	-0.066	0.22	-10000	0	-0.42	139	139
Gq family/GTP	0.009	0.037	-10000	0	-0.14	29	29
YES1	0.025	0.038	-10000	0	-0.18	9	9
GNAI2/GTP	0	0.026	-10000	0	-10000	0	0
PGD2/DP	0.014	0.001	-10000	0	-10000	0	0
SLC9A3R1	0.01	0.042	-10000	0	-0.15	29	29
FYN	0.02	0.052	-10000	0	-0.19	26	26
mol:NO	0.019	0.006	-10000	0	-0.11	1	1
GNA15	0.012	0.033	-10000	0	-0.12	26	26
PGK/cGMP	0.025	0.003	-10000	0	-10000	0	0
RhoA/GDP	0.015	0.035	-10000	0	-0.28	7	7
TP alpha/TGM2/GDP/G beta/gamma	0.034	0.028	-10000	0	-10000	0	0
NOS3	0.019	0.006	-10000	0	-0.11	1	1
RAC1	0.015	0.035	-10000	0	-0.29	7	7
PRKCA	-0.047	0.17	-10000	0	-0.32	139	139
PRKCB	-0.052	0.17	-10000	0	-0.33	139	139
PRKCE	-0.049	0.17	-10000	0	-0.33	139	139
PRKCD	-0.057	0.18	-10000	0	-0.36	139	139
PRKCG	-0.055	0.18	-10000	0	-0.35	139	139
muscle contraction	-0.075	0.23	-10000	0	-0.44	139	139
PRKCZ	-0.048	0.17	-10000	0	-0.32	139	139
ARR3	0.019	0	-10000	0	-10000	0	0
TXA2/TP beta	0.039	0.009	-10000	0	-10000	0	0
PRKCQ	-0.05	0.17	-10000	0	-0.33	139	139
MAPKKK cascade	-0.066	0.21	-10000	0	-0.4	139	139
SELE	-0.039	0.15	-10000	0	-0.28	139	139
TP beta/GNAI2/GDP/G beta/gamma	0.027	0.051	-10000	0	-0.22	15	15
ROCK1	0.016	0.031	-10000	0	-0.26	6	6
GNA14	0.015	0.022	-10000	0	-0.11	15	15
chemotaxis	-0.11	0.29	-10000	0	-0.58	139	139
GNA12	-0.005	0.082	-10000	0	-0.27	43	43
GNA13	0.016	0.021	-10000	0	-0.11	14	14
GNA11	0.003	0.068	-10000	0	-0.29	27	27
Rac1/GTP	0.011	0.024	-10000	0	-0.2	7	7

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.012	0.08	-9999	-0.17	91	91
EPHB2	0.013	0.027	-9999	-0.11	24	24
Syndecan-2/TACI	-0.003	0.065	-9999	-0.15	74	74
LAMA1	0	0	-9999	-10000	0	0
Syndecan-2/alpha2 ITGB1	-0.007	0.08	-9999	-0.14	113	113
HRAS	0.009	0.055	-9999	-0.28	18	18
Syndecan-2/CASK	-0.015	0.061	-9999	-0.16	74	74
ITGA5	-0.002	0.07	-9999	-0.19	53	53
BAX	0.013	0.097	-9999	-0.94	5	5
EPB41	0.019	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.006	0.066	-9999	-0.15	80	80
LAMA3	0.01	0.034	-9999	-0.11	38	38
EZR	0	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.037	0.11	-9999	-0.21	129	129
Syndecan-2/MMP2	-0.027	0.091	-9999	-0.18	117	117
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.003	0.067	-9999	-0.19	49	49
dendrite morphogenesis	-0.006	0.066	-9999	-0.16	74	74
Syndecan-2/GM-CSF	-0.003	0.064	-9999	-0.15	74	74
determination of left/right symmetry	0.007	0.036	-9999	-0.21	9	9
Syndecan-2/PKC delta	-0.006	0.066	-9999	-0.16	75	75
GNB2L1	0.018	0.019	-9999	-0.29	2	2
MAPK3	0.001	0.057	-9999	-0.13	74	74
MAPK1	-0.002	0.064	-9999	-0.15	75	75
Syndecan-2/RACK1	0.004	0.067	-9999	-0.14	85	85
NF1	0.019	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.007	0.036	-9999	-0.21	9	9
ITGA2	-0.026	0.095	-9999	-0.19	113	113
MAPK8	0.014	0.048	-9999	-0.38	6	6
Syndecan-2/alpha2/beta1 Integrin	-0.012	0.075	-9999	-0.14	110	110
Syndecan-2/Kininogen	-0.003	0.064	-9999	-0.15	74	74
ITGB1	0.019	0	-9999	-10000	0	0
SRC	0.002	0.06	-9999	-0.12	85	85
Syndecan-2/CASK/Protein 4.1	-0.002	0.058	-9999	-0.14	74	74
extracellular matrix organization	-0.009	0.07	-9999	-0.16	82	82
actin cytoskeleton reorganization	-0.012	0.079	-9999	-0.17	91	91
Syndecan-2/Caveolin-2/Ras	-0.024	0.094	-9999	-0.17	129	129
Syndecan-2/Laminin alpha3	-0.007	0.067	-9999	-0.16	75	75
Syndecan-2/RasGAP	0.005	0.078	-9999	-0.14	100	100
alpha5/beta1 Integrin	0.013	0.049	-9999	-0.19	24	24
PRKCD	0.012	0.029	-9999	-0.11	27	27
Syndecan-2 dimer	-0.006	0.066	-9999	-0.16	74	74
GO:0007205	0.002	0.014	-9999	-0.14	4	4
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.007	0.074	-9999	-0.22	24	24
RHOA	0.015	0.035	-9999	-0.29	7	7
SDCBP	0.011	0.05	-9999	-0.29	14	14
TNFRSF13B	0.019	0.006	-9999	-10000	0	0
RASA1	0.003	0.069	-9999	-0.28	29	29
alpha2/beta1 Integrin	-0.003	0.067	-9999	-0.19	49	49
Syndecan-2/Synbindin	-0.005	0.071	-9999	-0.16	76	76
TGFB1	0.007	0.049	-9999	-0.16	37	37
CASP3	-0.005	0.065	-9999	-0.15	75	75
FN1	0.001	0.07	-9999	-0.26	34	34
Syndecan-2/IL8	-0.062	0.1	-9999	-0.2	169	169
SDC2	0.007	0.036	-9999	-0.21	9	9
KNG1	0.019	0.006	-9999	-0.11	1	1
Syndecan-2/Neurofibromin	-0.003	0.064	-9999	-0.15	74	74
TRAPPC4	0.014	0.038	-9999	-0.27	9	9
CSF2	0.019	0	-9999	-10000	0	0
Syndecan-2/TGFB1	-0.009	0.07	-9999	-0.16	82	82
Syndecan-2/Syntenin/PI-4-5-P2	-0.006	0.067	-9999	-0.15	80	80
Syndecan-2/Ezrin	-0.004	0.063	-9999	-0.15	76	76
PRKACA	0.001	0.057	-9999	-0.13	74	74
angiogenesis	-0.062	0.1	-9999	-0.2	169	169
MMP2	-0.027	0.1	-9999	-0.22	103	103
IL8	-0.091	0.13	-9999	-0.21	254	254
calcineurin-NFAT signaling pathway	-0.003	0.064	-9999	-0.15	74	74

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.018	0.094	-9999	-0.18	117	117
alphaM/beta2 Integrin/GPIbA	0.008	0.067	-9999	-0.15	74	74
alphaM/beta2 Integrin/proMMP-9	-0.06	0.1	-9999	-0.17	201	201
PLAUR	-0.009	0.078	-9999	-0.18	73	73
HMGB1	0.019	0.014	-9999	-0.29	1	1
alphaM/beta2 Integrin/Talin	-0.004	0.08	-9999	-0.16	90	90
AGER	0.019	0.012	-9999	-0.12	4	4
RAP1A	0.018	0.019	-9999	-0.29	2	2
SELPLG	0.018	0.014	-9999	-0.11	6	6
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	0.024	0.068	-9999	-0.19	8	8
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.096	0.13	-9999	-0.21	270	270
CYR61	-0.058	0.12	-9999	-0.22	167	167
TLN1	-0.003	0.065	-9999	-0.16	64	64
Rap1/GTP	-0.014	0.055	-9999	-0.24	16	16
RHOA	0.015	0.035	-9999	-0.29	7	7
P-selectin oligomer	0.018	0.011	-9999	-0.11	4	4
MYH2	0.015	0.061	-9999	-0.22	16	16
MST1R	0.017	0.015	-9999	-0.11	7	7
leukocyte activation during inflammatory response	0.015	0.057	-9999	-0.12	74	74
APOB	0.018	0.011	-9999	-0.11	4	4
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.027	0.1	-9999	-0.22	103	103
JAM3	-0.007	0.085	-9999	-0.28	46	46
GP1BA	0.019	0	-9999	-10000	0	0
alphaM/beta2 Integrin/CTGF	-0.024	0.097	-9999	-0.18	133	133
alphaM/beta2 Integrin	0.001	0.072	-9999	-0.27	16	16
JAM3 homodimer	-0.007	0.085	-9999	-0.28	46	46
ICAM2	0.011	0.041	-9999	-0.15	26	26
ICAM1	0.005	0.04	-9999	-0.11	57	57
phagocytosis triggered by activation of immune response cell surface activating receptor	0.001	0.072	-9999	-0.27	16	16
cell adhesion	0.008	0.066	-9999	-0.15	74	74
NFKB1	0.013	0.067	-9999	-0.2	12	12
THY1	-0.019	0.097	-9999	-0.24	78	78
RhoA/GDP	0.011	0.024	-9999	-0.2	7	7
Lipoprotein(a)	0.025	0.007	-9999	-10000	0	0
alphaM/beta2 Integrin/LRP/tPA	-0.027	0.11	-9999	-0.18	142	142
IL6	0.005	0.073	-9999	-0.28	1	1
ITGB2	-0.032	0.11	-9999	-0.23	109	109
elevation of cytosolic calcium ion concentration	-0.017	0.1	-9999	-0.18	118	118
alphaM/beta2 Integrin/JAM2/JAM3	-0.007	0.11	-9999	-0.19	115	115
JAM2	-0.008	0.087	-9999	-0.28	49	49
alphaM/beta2 Integrin/ICAM1	0.017	0.067	-9999	-0.12	74	74
alphaM/beta2 Integrin/uPA/Plg	-0.003	0.085	-9999	-0.16	95	95
RhoA/GTP	0.011	0.064	-9999	-0.24	16	16
positive regulation of phagocytosis	-0.014	0.11	-9999	-0.26	78	78
Ron/MSP	0.025	0.017	-9999	-10000	0	0
alphaM/beta2 Integrin/uPAR/uPA	-0.016	0.1	-9999	-0.18	118	118
alphaM/beta2 Integrin/uPAR	-0.008	0.087	-9999	-0.17	102	102
PLAU	-0.023	0.087	-9999	-0.16	120	120
PLAT	-0.042	0.11	-9999	-0.22	135	135
actin filament polymerization	0.015	0.06	-9999	-0.22	16	16
MST1	0.016	0.02	-9999	-0.11	13	13
alphaM/beta2 Integrin/lipoprotein(a)	0.018	0.059	-9999	-0.12	74	74
TNF	0.015	0.061	-9999	-0.28	1	1
RAP1B	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.016	0.09	-9999	-0.17	104	104
fibrinolysis	-0.004	0.084	-9999	-0.16	95	95
HCK	-0.034	0.11	-9999	-0.21	121	121
dendritic cell antigen processing and presentation	0.001	0.072	-9999	-0.27	16	16
VTN	0.018	0.01	-9999	-0.11	3	3
alphaM/beta2 Integrin/CYR61	-0.036	0.1	-9999	-0.17	164	164
LPA	0.019	0	-9999	-10000	0	0
LRP1	-0.007	0.079	-9999	-0.29	33	33
cell migration	-0.07	0.11	-9999	-0.18	207	207
FN1	0.001	0.07	-9999	-0.26	34	34
alphaM/beta2 Integrin/Thy1	-0.014	0.092	-9999	-0.17	114	114
MPO	0.019	0	-9999	-10000	0	0
KNG1	0.019	0.006	-9999	-0.11	1	1
RAP1/GDP	0.012	0.011	-9999	-0.16	2	2
ROCK1	0.014	0.064	-9999	-0.24	16	16
ELA2	0.019	0	-9999	-10000	0	0
PLG	0.019	0	-9999	-10000	0	0
CTGF	-0.037	0.11	-9999	-0.29	79	79
alphaM/beta2 Integrin/Hck	-0.02	0.11	-9999	-0.21	116	116
ITGAM	0.02	0.003	-9999	-10000	0	0
alphaM/beta2 Integrin/P-Selectin/PSGL1	0.019	0.064	-9999	-0.13	74	74
HP	-0.014	0.056	-9999	-0.11	132	132
leukocyte adhesion	-0.016	0.13	-9999	-0.31	58	58
SELP	0.018	0.011	-9999	-0.11	4	4

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.011	0.014	-10000	0	-0.081	8	8
RAS family/GTP	-0.022	0.098	-10000	0	-0.2	72	72
NFATC4	-0.01	0.064	0.15	13	-0.14	29	42
ERBB2IP	0	0.074	-10000	0	-0.28	34	34
HSP90 (dimer)	0.018	0.019	-10000	0	-0.29	2	2
mammary gland morphogenesis	-0.021	0.073	0.17	4	-0.14	111	115
JUN	0.001	0.081	-10000	0	-0.37	8	8
HRAS	0.009	0.055	-10000	0	-0.28	18	18
DOCK7	-0.023	0.069	0.16	9	-0.14	111	120
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.022	0.072	0.17	7	-0.14	110	117
AKT1	0.001	0.039	-10000	0	-0.17	25	25
BAD	0.012	0.015	-10000	0	-0.082	9	9
MAPK10	-0.011	0.055	0.12	5	-0.15	40	45
mol:GTP	0	0.001	-10000	0	-0.004	41	41
ErbB2/ErbB3/neuregulin 1 beta	-0.021	0.078	0.18	6	-0.15	111	117
RAF1	-0.027	0.1	-10000	0	-0.22	77	77
ErbB2/ErbB3/neuregulin 2	-0.028	0.065	-10000	0	-0.14	105	105
STAT3	-0.043	0.25	-10000	0	-0.95	37	37
cell migration	-0.011	0.06	0.13	5	-0.16	37	42
mol:PI-3-4-5-P3	-0.001	0.001	0.003	6	-0.003	115	121
cell proliferation	-0.062	0.23	-10000	0	-0.58	66	66
FOS	-0.058	0.2	-10000	0	-0.45	97	97
NRAS	-0.01	0.086	-10000	0	-0.28	44	44
mol:Ca2+	-0.021	0.073	0.17	4	-0.14	111	115
MAPK3	-0.043	0.18	-10000	0	-0.5	49	49
MAPK1	-0.053	0.21	-10000	0	-0.56	54	54
JAK2	-0.019	0.072	0.16	10	-0.14	112	122
NF2	0.013	0.007	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.031	0.084	-10000	0	-0.18	112	112
NRG1	0.018	0.002	-10000	0	-10000	0	0
GRB2/SOS1	0.011	0.026	-10000	0	-0.17	10	10
MAPK8	-0.022	0.093	0.18	4	-0.19	107	111
MAPK9	-0.003	0.046	0.12	10	-0.12	14	24
ERBB2	0.013	0.072	0.29	33	-10000	0	33
ERBB3	-0.082	0.12	-10000	0	-0.19	257	257
SHC1	0.004	0.052	-10000	0	-0.14	48	48
RAC1	0.015	0.035	-10000	0	-0.29	7	7
apoptosis	0.001	0.046	0.24	16	-10000	0	16
STAT3 (dimer)	-0.041	0.24	-10000	0	-0.93	37	37
RNF41	0.012	0.014	-10000	0	-0.056	15	15
FRAP1	0.012	0.011	-10000	0	-0.065	8	8
RAC1-CDC42/GTP	-0.025	0.045	-10000	0	-0.13	29	29
ErbB2/ErbB2/HSP90 (dimer)	0.025	0.048	0.21	32	-0.17	1	33
CHRNA1	-0.025	0.14	-10000	0	-0.37	49	49
myelination	-0.008	0.063	0.15	13	-0.17	12	25
PPP3CB	-0.017	0.069	0.16	10	-0.13	112	122
KRAS	0.011	0.048	-10000	0	-0.28	14	14
RAC1-CDC42/GDP	-0.01	0.081	-10000	0	-0.15	114	114
NRG2	0.019	0.006	-10000	0	-0.11	1	1
mol:GDP	-0.031	0.084	-10000	0	-0.18	112	112
SOS1	0	0.001	-10000	0	-0.003	17	17
MAP2K2	-0.025	0.1	-10000	0	-0.23	69	69
SRC	0.019	0	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.001	-10000	0	-0.003	7	7
PTPN11	-0.017	0.073	0.17	11	-0.13	112	123
MAP2K1	-0.058	0.19	-10000	0	-0.46	64	64
heart morphogenesis	-0.021	0.073	0.17	4	-0.14	111	115
RAS family/GDP	-0.02	0.099	-10000	0	-0.2	71	71
GRB2	0.014	0.039	-10000	0	-0.26	10	10
PRKACA	0.009	0.008	-10000	0	-10000	0	0
CHRNE	0.008	0.026	-10000	0	-0.15	8	8
HSP90AA1	0.018	0.019	-10000	0	-0.29	2	2
activation of caspase activity	-0.001	0.039	0.17	25	-10000	0	25
nervous system development	-0.021	0.073	0.17	4	-0.14	111	115
CDC42	0.017	0.016	-10000	0	-0.11	8	8

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.004	0.036	-10000	0	-0.18	18	18
GNB1/GNG2	0.015	0.035	-10000	0	-0.14	21	21
regulation of S phase of mitotic cell cycle	-0.011	0.09	-10000	0	-0.2	83	83
GNAO1	-0.014	0.085	-10000	0	-0.2	81	81
HRAS	0.008	0.055	-10000	0	-0.28	18	18
SHBG/T-DHT	0.013	0	-10000	0	-10000	0	0
PELP1	0.014	0.036	-10000	0	-0.29	7	7
AKT1	0.001	0.042	-10000	0	-0.17	28	28
MAP2K1	0	0.07	-10000	0	-0.14	76	76
T-DHT/AR	0.01	0.017	-10000	0	-0.071	22	22
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	-10000	0	-0.007	83	83
GNAI2	0	0.073	-10000	0	-0.28	34	34
GNAI3	0.014	0.038	-10000	0	-0.29	8	8
GNAI1	-0.047	0.11	-10000	0	-0.2	158	158
mol:GDP	-0.019	0.044	-10000	0	-0.19	16	16
cell proliferation	-0.05	0.18	-10000	0	-0.41	92	92
PIK3CA	-0.011	0.085	-10000	0	-0.22	65	65
FOS	-0.1	0.29	-10000	0	-0.74	89	89
mol:Ca2+	-0.012	0.03	-10000	0	-0.058	132	132
MAPK3	-0.027	0.12	-10000	0	-0.27	94	94
MAPK1	-0.031	0.14	-10000	0	-0.27	92	92
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
mol:IP3	-0.001	0.002	-10000	0	-0.004	83	83
cAMP biosynthetic process	0.012	0.02	0.065	35	-10000	0	35
GNG2	0	0	-10000	0	-10000	0	0
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.004	83	83
HRAS/GTP	0.017	0.046	-10000	0	-0.15	22	22
actin cytoskeleton reorganization	-0.002	0.068	-10000	0	-0.14	84	84
SRC	0.019	0.001	-10000	0	-10000	0	0
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.004	83	83
PI3K	-0.011	0.078	-10000	0	-0.17	87	87
apoptosis	0.052	0.18	0.43	91	-10000	0	91
T-DHT/AR/PELP1	0.019	0.026	-10000	0	-0.16	7	7
HRAS/GDP	-0.001	0.061	-10000	0	-0.22	20	20
CREB1	-0.057	0.2	-10000	0	-0.46	90	90
RAC1-CDC42/GTP	0.003	0.071	-10000	0	-0.14	84	84
AR	0.013	0.026	-10000	0	-0.11	22	22
GNB1	0.007	0.061	-10000	0	-0.29	21	21
RAF1	0.005	0.06	-10000	0	-0.19	26	26
RAC1-CDC42/GDP	0.012	0.057	-10000	0	-0.19	19	19
T-DHT/AR/PELP1/Src	0.029	0.026	-10000	0	-0.14	7	7
MAP2K2	0.001	0.067	-10000	0	-0.13	73	73
T-DHT/AR/PELP1/Src/PI3K	-0.011	0.091	-10000	0	-0.2	83	83
GNAZ	-0.008	0.082	-10000	0	-0.24	55	55
SHBG	0.019	0	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.064	0.2	-10000	0	-0.48	73	73
mol:T-DHT	0	0.001	0.002	2	-0.002	77	79
RAC1	0.015	0.035	-10000	0	-0.29	7	7
GNRH1	0.01	0	-10000	0	-10000	0	0
Gi family/GTP	-0.041	0.1	-10000	0	-0.2	135	135
CDC42	0.017	0.016	-10000	0	-0.11	8	8

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.006	0.086	-9999	-0.21	50	50
NF kappa B1 p50/RelA/I kappa B alpha	0.003	0.12	-9999	-0.29	57	57
alphaV/beta3 Integrin/Osteopontin/Src	-0.006	0.095	-9999	-0.23	73	73
AP1	-0.033	0.17	-9999	-0.35	93	93
ILK	-0.004	0.097	-9999	-0.28	44	44
bone resorption	-0.016	0.11	-9999	-0.25	74	74
PTK2B	0.018	0.013	-9999	-0.11	5	5
PYK2/p130Cas	0.009	0.095	-9999	-0.22	58	58
ITGAV	0	0.071	-9999	-0.26	32	32
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.015	0.083	-9999	-0.19	89	89
alphaV/beta3 Integrin/Osteopontin	0.008	0.095	-9999	-0.21	73	73
MAP3K1	-0.002	0.084	-9999	-0.19	74	74
JUN	-0.002	0.077	-9999	-0.28	37	37
MAPK3	-0.006	0.095	-9999	-0.22	65	65
MAPK1	-0.009	0.1	-9999	-0.24	66	66
Rac1/GDP	0.011	0.024	-9999	-0.2	7	7
NFKB1	0.014	0.038	-9999	-0.22	12	12
MAPK8	-0.001	0.08	-9999	-0.2	57	57
ITGB3	0.016	0.019	-9999	-0.12	2	2
NFKBIA	-0.012	0.12	-9999	-0.3	59	59
FOS	-0.047	0.12	-9999	-0.22	146	146
CD44	-0.039	0.12	-9999	-0.25	115	115
CHUK	0.016	0.024	-9999	-0.15	9	9
PLAU	-0.068	0.28	-9999	-1	39	39
NF kappa B1 p50/RelA	0.005	0.12	-9999	-0.3	53	53
BCAR1	0	0	-9999	-10000	0	0
RELA	0.018	0.02	-9999	-0.23	3	3
alphaV beta3 Integrin	0.013	0.058	-9999	-0.18	35	35
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.008	0.098	-9999	-0.22	75	75
VAV3	-0.019	0.1	-9999	-0.24	79	79
MAP3K14	-0.003	0.089	-9999	-0.19	77	77
ROCK2	0.015	0.022	-9999	-0.11	15	15
SPP1	-0.013	0.095	-9999	-0.3	51	51
RAC1	0.015	0.035	-9999	-0.29	7	7
Rac1/GTP	-0.016	0.1	-9999	-0.25	69	69
MMP2	-0.05	0.17	-9999	-0.37	94	94

×

EPHB forward 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	0.022	0.016	-10000	0	-10000	0	0
cell-cell adhesion	0.027	0.054	0.17	50	-10000	0	50
Ephrin B/EPHB2/RasGAP	0.013	0.08	-10000	0	-0.14	94	94
ITSN1	0.016	0.031	-10000	0	-0.24	7	7
PIK3CA	-0.011	0.085	-10000	0	-0.22	65	65
SHC1	0.004	0.052	-10000	0	-0.14	48	48
Ephrin B1/EPHB3	0.021	0.019	-10000	0	-10000	0	0
Ephrin B1/EPHB1	0.012	0.033	-10000	0	-0.16	6	6
HRAS/GDP	-0.037	0.086	-10000	0	-0.21	88	88
Ephrin B/EPHB1/GRB7	0.01	0.074	-10000	0	-0.14	88	88
Endophilin/SYNJ1	0.001	0.054	-10000	0	-0.12	83	83
KRAS	0.011	0.048	-10000	0	-0.28	14	14
Ephrin B/EPHB1/Src	0.011	0.073	-10000	0	-0.13	88	88
endothelial cell migration	-0.017	0.097	-10000	0	-0.17	134	134
GRB2	0.014	0.039	-10000	0	-0.26	10	10
GRB7	0.016	0.019	-10000	0	-0.11	11	11
PAK1	0.005	0.054	-10000	0	-0.11	83	83
HRAS	0.009	0.055	-10000	0	-0.28	18	18
RRAS	-0.006	0.067	-10000	0	-0.14	89	89
DNM1	0.017	0.017	-10000	0	-0.11	9	9
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.008	0.067	-10000	0	-0.14	88	88
lamellipodium assembly	-0.027	0.054	-10000	0	-0.17	50	50
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.011	0.092	-10000	0	-0.24	45	45
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
EPHB2	0.013	0.027	-10000	0	-0.11	24	24
EPHB3	0.01	0.032	-10000	0	-0.11	35	35
EPHB1	-0.005	0.057	-10000	0	-0.12	91	91
EPHB4	0.019	0.006	-10000	0	-0.11	1	1
mol:GDP	-0.017	0.1	-10000	0	-0.24	83	83
Ephrin B/EPHB2	0.011	0.063	-10000	0	-0.12	83	83
Ephrin B/EPHB3	0.01	0.063	-10000	0	-0.12	83	83
JNK cascade	0.011	0.043	-10000	0	-0.17	18	18
Ephrin B/EPHB1	0.002	0.07	-10000	0	-0.14	88	88
RAP1/GDP	-0.008	0.095	-10000	0	-0.21	83	83
EFNB2	-0.035	0.11	-10000	0	-0.25	105	105
EFNB3	0.016	0.022	-10000	0	-0.13	11	11
EFNB1	0.019	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.009	0.072	-10000	0	-0.15	97	97
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0.018	0.019	-10000	0	-0.29	2	2
CDC42/GTP	0.002	0.087	-10000	0	-0.18	84	84
Rap1/GTP	-0.03	0.061	-10000	0	-0.19	51	51
axon guidance	0.022	0.016	-10000	0	-10000	0	0
MAPK3	-0.004	0.085	-10000	0	-0.22	46	46
MAPK1	-0.007	0.092	-10000	0	-0.23	52	52
Rac1/GDP	-0.008	0.1	-10000	0	-0.23	83	83
actin cytoskeleton reorganization	-0.037	0.077	-10000	0	-0.2	68	68
CDC42/GDP	-0.007	0.098	-10000	0	-0.22	83	83
PI3K	-0.015	0.099	-10000	0	-0.17	134	134
EFNA5	0.019	0.006	-10000	0	-0.11	1	1
Ephrin B2/EPHB4	-0.006	0.066	-10000	0	-0.16	83	83
Ephrin B/EPHB2/Intersectin/N-WASP	-0.001	0.081	-10000	0	-0.17	85	85
CDC42	0.017	0.016	-10000	0	-0.11	8	8
RAS family/GTP	-0.036	0.076	-10000	0	-0.2	70	70
PTK2	0.002	0.052	-10000	0	-0.27	18	18
MAP4K4	0.011	0.043	-10000	0	-0.17	18	18
SRC	0.019	0	-10000	0	-10000	0	0
KALRN	0.017	0.018	-10000	0	-0.11	10	10
Intersectin/N-WASP	0.024	0.03	-10000	0	-0.19	10	10
neuron projection morphogenesis	0.009	0.079	-10000	0	-0.18	54	54
MAP2K1	-0.008	0.089	-10000	0	-0.23	47	47
WASL	0.016	0.03	-10000	0	-0.29	5	5
Ephrin B1/EPHB1-2/NCK1	0.027	0.044	-10000	0	-0.14	12	12
cell migration	-0.01	0.097	-10000	0	-0.24	51	51
NRAS	-0.01	0.086	-10000	0	-0.29	42	42
SYNJ1	0.001	0.054	-10000	0	-0.12	83	83
PXN	0.018	0.011	-10000	0	-0.11	4	4
TF	-0.026	0.073	-10000	0	-0.16	104	104
HRAS/GTP	0.001	0.079	-10000	0	-0.18	54	54
Ephrin B1/EPHB1-2	0.019	0.036	-10000	0	-0.11	14	14
cell adhesion mediated by integrin	0.01	0.052	0.12	81	-10000	0	81
RAC1	0.015	0.035	-10000	0	-0.29	7	7
mol:GTP	0.002	0.078	-10000	0	-0.14	99	99
RAC1-CDC42/GTP	-0.026	0.055	-10000	0	-0.16	54	54
RASA1	0.003	0.069	-10000	0	-0.28	29	29
RAC1-CDC42/GDP	0	0.1	-10000	0	-0.22	83	83
ruffle organization	-0.002	0.077	-10000	0	-0.19	54	54
NCK1	0.014	0.036	-10000	0	-0.19	14	14
receptor internalization	0.003	0.052	-10000	0	-0.11	83	83
Ephrin B/EPHB2/KALRN	0.019	0.066	-10000	0	-0.12	83	83
ROCK1	0.019	0.016	-10000	0	-10000	0	0
RAS family/GDP	-0.04	0.083	-10000	0	-0.22	68	68
Rac1/GTP	-0.028	0.056	-10000	0	-0.18	50	50
Ephrin B/EPHB1/Src/Paxillin	-0.005	0.076	-10000	0	-0.17	88	88

×

Noncanonical Wnt signaling pathway

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
NFATC2	0	0	-9999	-10000	0	0
GNB1/GNG2	-0.026	0.11	-9999	-0.28	55	55
mol:DAG	-0.023	0.1	-9999	-0.26	55	55
PLCG1	-0.024	0.11	-9999	-0.27	55	55
YES1	-0.032	0.11	-9999	-0.28	58	58
FZD3	-0.028	0.1	-9999	-0.22	103	103
FZD6	-0.02	0.076	-9999	-0.14	128	128
G protein	-0.024	0.11	-9999	-0.29	55	55
MAP3K7	-0.018	0.097	-9999	-0.23	62	62
mol:Ca2+	-0.022	0.1	-9999	-0.26	55	55
mol:IP3	-0.023	0.1	-9999	-0.26	55	55
NLK	-0.006	0.16	-9999	-0.91	16	16
GNB1	0.007	0.061	-9999	-0.29	21	21
CAMK2A	-0.018	0.097	-9999	-0.24	57	57
MAP3K7IP1	0.019	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.033	0.11	-9999	-0.2	134	134
CSNK1A1	0.014	0.038	-9999	-0.29	8	8
GNAS	-0.03	0.11	-9999	-0.27	54	54
GO:0007205	-0.025	0.1	-9999	-0.27	55	55
WNT6	0.019	0	-9999	-10000	0	0
WNT4	0.018	0.013	-9999	-0.11	5	5
NFAT1/CK1 alpha	-0.019	0.11	-9999	-0.25	61	61
GNG2	0	0	-9999	-10000	0	0
WNT5A	-0.028	0.1	-9999	-0.24	98	98
WNT11	0.017	0.016	-9999	-0.11	8	8
CDC42	-0.028	0.1	-9999	-0.25	62	62

×

BCR 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
JUN	-0.017	0.12	0.19	1	-0.29	70	71
IKBKB	0.008	0.072	0.2	6	-0.21	24	30
AKT1	-0.018	0.072	0.16	3	-0.17	66	69
IKBKG	0.005	0.073	0.18	2	-0.21	32	34
CALM1	-0.03	0.14	0.18	18	-0.36	64	82
PIK3CA	-0.011	0.085	-10000	0	-0.22	65	65
MAP3K1	-0.017	0.13	-10000	0	-0.39	44	44
MAP3K7	0.006	0.059	-10000	0	-0.24	26	26
mol:Ca2+	-0.031	0.15	0.18	20	-0.38	61	81
DOK1	0.019	0	-10000	0	-10000	0	0
AP-1	-0.016	0.09	0.14	6	-0.21	75	81
LYN	-0.018	0.097	-10000	0	-0.25	72	72
BLNK	-0.036	0.1	-10000	0	-0.2	130	130
SHC1	0.004	0.052	-10000	0	-0.14	48	48
BCR complex	0.027	0.013	-10000	0	-0.14	2	2
CD22	-0.029	0.11	-10000	0	-0.3	59	59
CAMK2G	-0.027	0.14	0.18	18	-0.33	65	83
CSNK2A1	0.01	0.053	-10000	0	-0.29	16	16
INPP5D	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.041	0.081	-10000	0	-0.27	46	46
GO:0007205	-0.032	0.15	0.18	20	-0.38	61	81
SYK	-0.005	0.072	-10000	0	-0.18	62	62
ELK1	-0.025	0.14	0.18	20	-0.36	61	81
NFATC1	-0.018	0.1	-10000	0	-0.3	48	48
B-cell antigen/BCR complex	0.027	0.013	-10000	0	-0.14	2	2
PAG1/CSK	0.01	0.03	-10000	0	-0.2	11	11
NFKBIB	0.011	0.033	0.09	1	-0.11	16	17
HRAS	-0.026	0.13	0.17	8	-0.31	67	75
NFKBIA	0.013	0.029	0.09	1	-0.11	8	9
NF-kappa-B/RelA/I kappa B beta	0.016	0.03	0.092	1	-0.13	9	10
RasGAP/Csk	-0.011	0.081	-10000	0	-0.13	142	142
mol:GDP	-0.028	0.15	0.18	20	-0.36	62	82
PTEN	0.013	0.037	-10000	0	-0.18	16	16
CD79B	0.018	0.011	-10000	0	-0.11	4	4
NF-kappa-B/RelA/I kappa B alpha	0.017	0.028	0.092	2	-0.11	9	11
GRB2	0.014	0.039	-10000	0	-0.26	10	10
PI3K/BCAP/CD19	-0.052	0.17	-10000	0	-0.42	73	73
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
mol:IP3	-0.032	0.15	0.18	20	-0.39	61	81
CSK	0.013	0.044	-10000	0	-0.29	11	11
FOS	-0.044	0.14	0.17	13	-0.35	68	81
CHUK	0.003	0.075	0.18	2	-0.22	34	36
IBTK	0.014	0.039	-10000	0	-0.26	10	10
CARD11/BCL10/MALT1/TAK1	-0.019	0.13	0.22	2	-0.32	64	66
PTPN6	-0.029	0.12	-10000	0	-0.36	46	46
RELA	0.018	0.02	-10000	0	-0.23	3	3
BCL2A1	0.007	0.03	-10000	0	-0.082	32	32
VAV2	-0.028	0.12	-10000	0	-0.37	47	47
ubiquitin-dependent protein catabolic process	0.015	0.032	0.092	1	-0.11	13	14
BTK	0.012	0.009	-10000	0	-10000	0	0
CD19	-0.029	0.11	-10000	0	-0.36	42	42
MAP4K1	0.019	0.006	-10000	0	-0.11	1	1
CD72	0.016	0.019	-10000	0	-0.11	12	12
PAG1	0	0	-10000	0	-10000	0	0
MAPK14	-0.01	0.11	-10000	0	-0.33	45	45
SH3BP5	-0.003	0.075	-10000	0	-0.22	49	49
PIK3AP1	-0.034	0.16	0.19	20	-0.41	62	82
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.035	0.19	-10000	0	-0.48	66	66
RAF1	-0.024	0.13	0.16	8	-0.32	60	68
RasGAP/p62DOK/SHIP	-0.012	0.069	-10000	0	-0.12	139	139
CD79A	0.018	0.013	-10000	0	-0.11	5	5
re-entry into mitotic cell cycle	-0.016	0.09	0.14	6	-0.2	77	83
RASA1	0.003	0.069	-10000	0	-0.28	29	29
MAPK3	-0.013	0.11	0.15	7	-0.3	48	55
MAPK1	-0.016	0.11	0.15	7	-0.3	54	61
CD72/SHP1	-0.02	0.11	-10000	0	-0.34	45	45
NFKB1	0.014	0.038	-10000	0	-0.22	12	12
MAPK8	-0.009	0.11	-10000	0	-0.33	44	44
actin cytoskeleton organization	-0.021	0.11	-10000	0	-0.33	48	48
NF-kappa-B/RelA	0.029	0.072	0.18	1	-0.24	19	20
Calcineurin	-0.016	0.13	-10000	0	-0.3	71	71
PI3K	-0.052	0.11	-10000	0	-0.3	63	63
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.036	0.17	0.2	20	-0.43	62	82
SOS1	0	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.018	0.14	-10000	0	-0.46	40	40
DAPP1	-0.031	0.15	-10000	0	-0.5	40	40
cytokine secretion	-0.017	0.096	-10000	0	-0.28	49	49
mol:DAG	-0.032	0.15	0.18	20	-0.39	61	81
PLCG2	-0.002	0.068	-10000	0	-0.19	52	52
MAP2K1	-0.019	0.12	0.16	7	-0.32	52	59
B-cell antigen/BCR complex/FcgammaRIIB	-0.021	0.076	-10000	0	-0.15	115	115
mol:PI-3-4-5-P3	-0.04	0.078	0.16	4	-0.23	59	63
ETS1	-0.02	0.12	0.18	18	-0.3	64	82
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.005	0.11	-10000	0	-0.19	106	106
B-cell antigen/BCR complex/LYN	-0.034	0.12	-10000	0	-0.31	68	68
MALT1	0.013	0.036	-10000	0	-0.16	18	18
TRAF6	0.018	0.019	-10000	0	-0.29	2	2
RAC1	-0.023	0.12	-10000	0	-0.35	48	48
B-cell antigen/BCR complex/LYN/SYK	-0.01	0.12	-10000	0	-0.33	56	56
CARD11	-0.03	0.14	0.18	20	-0.36	61	81
FCGR2B	-0.076	0.12	-10000	0	-0.2	230	230
PPP3CA	0.002	0.069	-10000	0	-0.27	31	31
BCL10	0.016	0.028	-10000	0	-0.23	6	6
IKK complex	0.011	0.034	0.1	8	-0.085	18	26
PTPRC	-0.031	0.11	-10000	0	-0.23	108	108
PDPK1	-0.015	0.062	0.15	3	-0.16	57	60
PPP3CB	0.016	0.028	-10000	0	-0.16	10	10
PPP3CC	0.019	0	-10000	0	-10000	0	0
POU2F2	0.013	0.025	-10000	0	-0.082	17	17

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.011	0.043	-9999	-0.18	21	21
mol:S1P	0.001	0.001	-9999	-10000	0	0
S1P1/S1P/Gi	-0.048	0.14	-9999	-0.24	143	143
GNAO1	-0.012	0.085	-9999	-0.19	81	81
S1P/S1P3/G12/G13	0.012	0.045	-9999	-0.14	39	39
AKT1	-0.026	0.15	-9999	-0.6	31	31
AKT3	-0.056	0.14	-9999	-0.55	18	18
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.011	0.043	-9999	-0.18	21	21
GNAI2	0.002	0.074	-9999	-0.27	34	34
GNAI3	0.016	0.038	-9999	-0.29	8	8
GNAI1	-0.045	0.11	-9999	-0.2	158	158
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.001	0.001	-9999	-10000	0	0
S1PR2	0	0	-9999	-10000	0	0
EDG1	0.001	0.067	-9999	-0.22	39	39
mol:Ca2+	-0.037	0.12	-9999	-0.28	73	73
MAPK3	-0.031	0.11	-9999	-0.28	63	63
MAPK1	-0.035	0.12	-9999	-0.27	77	77
JAK2	-0.04	0.13	-9999	-0.28	87	87
CXCR4	-0.049	0.13	-9999	-0.27	97	97
FLT1	0.021	0.008	-9999	-0.11	2	2
RhoA/GDP	0.011	0.024	-9999	-0.2	7	7
Rac1/GDP	0.011	0.024	-9999	-0.2	7	7
SRC	-0.031	0.11	-9999	-0.26	73	73
S1P/S1P3/Gi	-0.037	0.12	-9999	-0.28	73	73
RAC1	0.015	0.035	-9999	-0.29	7	7
RhoA/GTP	-0.027	0.12	-9999	-0.3	55	55
VEGFA	-0.065	0.13	-9999	-0.22	188	188
S1P/S1P2/Gi	-0.041	0.12	-9999	-0.21	143	143
VEGFR1 homodimer/VEGFA homodimer	-0.028	0.092	-9999	-0.19	119	119
RHOA	0.015	0.035	-9999	-0.29	7	7
S1P/S1P3/Gq	0.012	0.045	-9999	-0.16	29	29
GNAQ	0.015	0.023	-9999	-0.11	17	17
GNAZ	-0.006	0.082	-9999	-0.24	55	55
G12/G13	0.009	0.059	-9999	-0.19	39	39
GNA14	0.015	0.022	-9999	-0.11	15	15
GNA15	0.012	0.033	-9999	-0.12	26	26
GNA12	-0.005	0.082	-9999	-0.27	43	43
GNA13	0.016	0.021	-9999	-0.11	14	14
GNA11	0.003	0.068	-9999	-0.29	27	27
Rac1/GTP	-0.027	0.12	-9999	-0.31	54	54

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	-0.016	0.14	-10000	0	-0.28	84	84
adherens junction organization	0	0.097	-10000	0	-0.3	38	38
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.033	0.13	-10000	0	-0.29	70	70
FMN1	0.001	0.086	-10000	0	-0.3	28	28
mol:IP3	-0.009	0.11	-10000	0	-0.26	57	57
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.002	0.091	-10000	0	-0.32	28	28
CTNNB1	0.017	0.024	-10000	0	-0.3	3	3
AKT1	-0.008	0.12	-10000	0	-0.34	48	48
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.016	0.085	-10000	0	-0.39	16	16
CTNND1	0	0.075	-10000	0	-0.3	31	31
mol:PI-4-5-P2	0.005	0.085	-10000	0	-0.28	31	31
VASP	0.005	0.088	-10000	0	-0.3	29	29
ZYX	-0.006	0.11	-10000	0	-0.34	40	40
JUB	0.001	0.086	-10000	0	-0.3	28	28
EGFR(dimer)	-0.02	0.11	-10000	0	-0.29	50	50
E-cadherin/beta catenin-gamma catenin	0.027	0.037	-10000	0	-0.11	28	28
mol:PI-3-4-5-P3	-0.003	0.12	-10000	0	-0.27	57	57
PIK3CA	-0.011	0.087	-10000	0	-0.23	65	65
PI3K	-0.003	0.12	-10000	0	-0.28	57	57
FYN	-0.028	0.16	-10000	0	-0.4	70	70
mol:Ca2+	-0.008	0.11	-10000	0	-0.26	57	57
JUP	0.007	0.037	-10000	0	-0.11	47	47
PIK3R1	-0.015	0.096	-10000	0	-0.27	62	62
mol:DAG	-0.009	0.11	-10000	0	-0.26	57	57
CDH1	0.012	0.03	-10000	0	-0.11	28	28
RhoA/GDP	-0.033	0.12	-10000	0	-0.29	70	70
establishment of polarity of embryonic epithelium	0.005	0.087	-10000	0	-0.3	30	30
SRC	0.019	0	-10000	0	-10000	0	0
RAC1	0.015	0.035	-10000	0	-0.29	7	7
RHOA	0.015	0.035	-10000	0	-0.29	7	7
EGFR	-0.08	0.12	-10000	0	-0.18	267	267
CASR	-0.004	0.1	-10000	0	-0.24	57	57
RhoA/GTP	0	0.1	-10000	0	-0.28	45	45
AKT2	-0.003	0.11	-10000	0	-0.28	48	48
actin cable formation	0.004	0.086	-10000	0	-0.29	30	30
apoptosis	0.012	0.13	0.25	84	-10000	0	84
CTNNA1	0.011	0.05	-10000	0	-0.3	13	13
mol:GDP	-0.035	0.13	-10000	0	-0.28	81	81
PIP5K1A	0.005	0.087	-10000	0	-0.29	31	31
PLCG1	-0.009	0.11	-10000	0	-0.27	57	57
Rac1/GTP	-0.024	0.11	-10000	0	-0.28	50	50
homophilic cell adhesion	-0.001	0.003	-10000	0	-10000	0	0

×

PLK2 and PLK4 events

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
PLK2	-0.013	0.083	-9999	-0.19	83	83
PLK4	0.017	0.017	-9999	-0.11	9	9
regulation of centriole replication	-0.002	0.058	-9999	-0.18	40	40

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	0.018	0.057	-10000	0	-0.16	41	41
fibroblast growth factor receptor signaling pathway	0.017	0.057	-10000	0	-0.16	41	41
LAMA1	0	0	-10000	0	-10000	0	0
PRNP	-0.002	0.076	-10000	0	-0.26	41	41
GPC1/SLIT2	-0.007	0.068	-10000	0	-0.2	40	40
SMAD2	0.01	0.05	-10000	0	-0.15	41	41
GPC1/PrPc/Cu2+	-0.002	0.071	-10000	0	-0.19	57	57
GPC1/Laminin alpha1	-0.005	0.056	-10000	0	-0.14	62	62
TDGF1	0.018	0.014	-10000	0	-0.11	6	6
CRIPTO/GPC1	0.008	0.06	-10000	0	-0.2	37	37
APP/GPC1	0.005	0.069	-10000	0	-0.22	41	41
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0.006	0.059	-10000	0	-0.18	40	40
FLT1	0.019	0.008	-10000	0	-0.11	2	2
GPC1/TGFB/TGFBR1/TGFBR2	0.018	0.056	-10000	0	-0.16	42	42
SERPINC1	0.019	0.006	-10000	0	-0.11	1	1
FYN	-0.001	0.079	-10000	0	-0.27	38	38
FGR	0.003	0.058	-10000	0	-0.18	39	39
positive regulation of MAPKKK cascade	-0.037	0.15	-10000	0	-0.34	78	78
SLIT2	-0.005	0.05	-10000	0	-0.11	97	97
GPC1/NRG	0.009	0.058	-10000	0	-0.19	37	37
NRG1	0.019	0	-10000	0	-10000	0	0
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.031	0.094	-10000	0	-0.17	144	144
LYN	0.002	0.06	-10000	0	-0.19	39	39
mol:Spermine	-0.008	0.054	-10000	0	-0.2	37	37
cell growth	0.017	0.057	-10000	0	-0.16	41	41
BMP signaling pathway	0.009	0.082	0.22	62	-10000	0	62
SRC	0.009	0.049	-10000	0	-0.16	37	37
TGFBR1	0.019	0.006	-10000	0	-0.11	1	1
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.078	0.11	-10000	0	-0.17	272	272
GPC1	-0.009	0.082	-10000	0	-0.22	62	62
TGFBR1 (dimer)	0.019	0.006	-10000	0	-0.11	1	1
VEGFA	-0.068	0.13	-10000	0	-0.22	188	188
BLK	0.009	0.049	-10000	0	-0.16	37	37
HCK	-0.004	0.067	-10000	0	-0.21	41	41
FGF2	0.013	0.036	-10000	0	-0.16	19	19
FGFR1	0.019	0.008	-10000	0	-0.11	2	2
VEGFR1 homodimer	0.019	0.008	-10000	0	-0.11	2	2
TGFBR2	0.012	0.035	-10000	0	-0.15	21	21
cell death	0.005	0.069	-10000	0	-0.22	41	41
ATIII/GPC1	0.009	0.058	-10000	0	-0.19	37	37
PLA2G2A/GPC1	-0.058	0.094	-10000	0	-0.2	124	124
LCK	0.008	0.051	-10000	0	-0.17	37	37
neuron differentiation	0.009	0.058	-10000	0	-0.19	37	37
PrPc/Cu2+	0	0.052	-10000	0	-0.17	41	41
APP	0.013	0.042	-10000	0	-0.29	10	10
TGFBR2 (dimer)	0.012	0.035	-10000	0	-0.14	21	21

×

S1P1 pathway

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
VEGFR2 homodimer/VEGFA homodimer	-0.047	0.11	-9999	-0.2	149	149
PDGFRB	0.01	0.044	-9999	-0.18	21	21
SPHK1	-0.005	0.025	-9999	-10000	0	0
mol:S1P	0.001	0.037	-9999	-10000	0	0
S1P1/S1P/Gi	-0.064	0.19	-9999	-0.43	82	82
GNAO1	-0.014	0.086	-9999	-0.2	81	81
PDGFB-D/PDGFRB/PLCgamma1	-0.055	0.17	-9999	-0.44	62	62
PLCG1	-0.058	0.18	-9999	-0.45	68	68
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.01	0.043	-9999	-0.18	21	21
GNAI2	0	0.074	-9999	-0.28	34	34
GNAI3	0.014	0.038	-9999	-0.29	8	8
GNAI1	-0.047	0.11	-9999	-0.2	158	158
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.045	0.12	-9999	-0.35	42	42
S1P1/S1P	-0.034	0.11	-9999	-0.35	35	35
negative regulation of cAMP metabolic process	-0.063	0.19	-9999	-0.42	84	84
MAPK3	-0.059	0.18	-9999	-0.48	62	62
calcium-dependent phospholipase C activity	-0.001	0.002	-9999	-10000	0	0
Rac1/GDP	0.011	0.024	-9999	-0.2	7	7
RhoA/GDP	0.011	0.024	-9999	-0.2	7	7
KDR	-0.002	0.067	-9999	-0.19	38	38
PLCB2	-0.027	0.098	-9999	-0.31	35	35
RAC1	0.015	0.035	-9999	-0.29	7	7
RhoA/GTP	-0.042	0.085	-9999	-0.3	37	37
receptor internalization	-0.033	0.1	-9999	-0.32	36	36
PTGS2	-0.064	0.17	-9999	-0.55	41	41
Rac1/GTP	-0.042	0.087	-9999	-0.31	35	35
RHOA	0.015	0.035	-9999	-0.29	7	7
VEGFA	-0.07	0.13	-9999	-0.28	131	131
negative regulation of T cell proliferation	-0.063	0.19	-9999	-0.42	84	84
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.008	0.084	-9999	-0.24	55	55
MAPK1	-0.062	0.19	-9999	-0.49	64	64
S1P1/S1P/PDGFB-D/PDGFRB	-0.034	0.12	-9999	-0.36	42	42
ABCC1	0.014	0.024	-9999	-0.12	17	17

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	0.016	0.048	-9999	-0.19	25	25
AKT1	-0.08	0.21	-9999	-0.45	90	90
PTK2B	-0.034	0.11	-9999	-0.29	55	55
VEGFR2 homodimer/Frs2	0.006	0.089	-9999	-0.37	19	19
CAV1	-0.071	0.13	-9999	-0.22	197	197
CALM1	0.007	0.056	-9999	-0.21	28	28
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.034	0.12	-9999	-0.32	46	46
endothelial cell proliferation	-0.049	0.17	-9999	-0.39	66	66
mol:Ca2+	-0.041	0.13	-9999	-0.34	56	56
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.035	0.13	-9999	-0.31	62	62
RP11-342D11.1	-0.048	0.13	-9999	-0.34	53	53
CDH5	-0.016	0.087	-9999	-0.2	84	84
VEGFA homodimer	-0.017	0.079	-9999	-0.15	122	122
SHC1	0.004	0.052	-9999	-0.14	48	48
SHC2	0.001	0.071	-9999	-0.25	36	36
HRAS/GDP	-0.061	0.11	-9999	-0.31	64	64
SH2D2A	0.019	0.006	-9999	-0.11	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.027	0.14	-9999	-0.4	41	41
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.033	0.12	-9999	-0.32	46	46
VEGFR1 homodimer	0.019	0.008	-9999	-0.11	2	2
SHC/GRB2/SOS1	-0.033	0.14	-9999	-0.32	62	62
GRB10	-0.057	0.16	-9999	-0.41	67	67
PTPN11	0.015	0.033	-9999	-0.26	7	7
GRB2	0.014	0.039	-9999	-0.26	10	10
PAK1	0.017	0.017	-9999	-0.11	9	9
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.04	0.14	-9999	-0.32	70	70
HRAS	0.009	0.055	-9999	-0.28	18	18
VEGF/Rho/ROCK1/Integrin Complex	-0.033	0.14	-9999	-0.42	36	36
HIF1A	0.011	0.047	-9999	-0.26	14	14
FRS2	0.018	0.013	-9999	-0.11	5	5
oxygen and reactive oxygen species metabolic process	-0.035	0.13	-9999	-0.31	62	62
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.019	0.006	-9999	-0.11	1	1
Nck/Pak	0.023	0.029	-9999	-0.18	8	8
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.051	0.14	-9999	-0.35	64	64
mol:GDP	-0.038	0.13	-9999	-0.32	62	62
mol:NADP	-0.027	0.12	-9999	-0.38	35	35
eNOS/Hsp90	-0.018	0.12	-9999	-0.37	33	33
PIK3R1	-0.015	0.095	-9999	-0.27	62	62
mol:IP3	-0.042	0.13	-9999	-0.34	56	56
HIF1A/ARNT	0.023	0.033	-9999	-0.19	12	12
SHB	0.016	0.02	-9999	-0.11	13	13
VEGFA	-0.072	0.13	-9999	-0.23	188	188
VEGFC	0.01	0.033	-9999	-0.11	37	37
FAK1/Vinculin	-0.046	0.17	-9999	-0.43	55	55
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.015	0.035	-9999	-0.29	7	7
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.028	0.13	-9999	-0.31	55	55
PTPN6	0.005	0.057	-9999	-0.2	33	33
EPAS1	0.004	0.075	-9999	-0.27	28	28
mol:L-citrulline	-0.027	0.12	-9999	-0.38	35	35
ITGAV	0.003	0.067	-9999	-0.25	32	32
PIK3CA	-0.011	0.085	-9999	-0.22	65	65
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.023	0.12	-9999	-0.31	46	46
VEGFR2 homodimer/VEGFA homodimer	-0.04	0.15	-9999	-0.36	55	55
VEGFR2/3 heterodimer	0.006	0.089	-9999	-0.37	19	19
VEGFB	0.017	0.023	-9999	-0.29	3	3
MAPK11	-0.047	0.14	-9999	-0.36	52	52
VEGFR2 homodimer	-0.003	0.1	-9999	-0.4	23	23
FLT1	0.019	0.008	-9999	-0.11	2	2
NEDD4	0.009	0.033	-9999	-0.14	9	9
MAPK3	-0.037	0.12	-9999	-0.3	56	56
MAPK1	-0.039	0.12	-9999	-0.31	57	57
VEGFA145/NRP2	-0.037	0.093	-9999	-0.19	125	125
VEGFR1/2 heterodimer	0.006	0.089	-9999	-0.37	19	19
KDR	-0.003	0.1	-9999	-0.4	23	23
VEGFA165/NRP1/VEGFR2 homodimer	-0.031	0.13	-9999	-0.34	53	53
SRC	0.019	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	-0.038	0.12	-9999	-0.31	56	56
PI3K	-0.06	0.18	-9999	-0.4	83	83
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.036	0.12	-9999	-0.32	49	49
FES	-0.042	0.13	-9999	-0.35	53	53
GAB1	-0.062	0.17	-9999	-0.39	76	76
VEGFR2 homodimer/VEGFA homodimer/Src	-0.033	0.12	-9999	-0.32	46	46
CTNNB1	0.017	0.023	-9999	-0.29	3	3
SOS1	0	0	-9999	-10000	0	0
ARNT	0.019	0.006	-9999	-0.11	1	1
eNOS/Caveolin-1	-0.043	0.14	-9999	-0.34	58	58
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.04	0.13	-9999	-0.32	56	56
PI3K/GAB1	-0.076	0.2	-9999	-0.43	93	93
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.015	0.12	-9999	-0.29	47	47
PRKACA	0.019	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.014	0.088	-9999	-0.38	17	17
HSP90AA1	0.018	0.019	-9999	-0.29	2	2
CDC42	-0.042	0.13	-9999	-0.35	53	53
actin cytoskeleton reorganization	-0.033	0.12	-9999	-0.32	46	46
PTK2	-0.056	0.18	-9999	-0.46	53	53
EDG1	-0.048	0.15	-9999	-0.36	70	70
mol:DAG	-0.042	0.13	-9999	-0.34	56	56
CaM/Ca2+	-0.036	0.13	-9999	-0.34	57	57
MAP2K3	-0.037	0.12	-9999	-0.32	53	53
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.047	0.17	-9999	-0.41	67	67
PLCG1	-0.042	0.13	-9999	-0.34	56	56
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.021	0.12	-9999	-0.3	44	44
IQGAP1	-0.008	0.086	-9999	-0.27	49	49
YES1	0.005	0.061	-9999	-0.24	28	28
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.035	0.12	-9999	-0.33	47	47
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.04	0.12	-9999	-0.32	51	51
cell migration	-0.047	0.18	-9999	-0.41	68	68
mol:PI-3-4-5-P3	-0.056	0.17	-9999	-0.37	83	83
FYN	-0.019	0.1	-9999	-0.28	68	68
VEGFB/NRP1	-0.038	0.12	-9999	-0.32	53	53
mol:NO	-0.027	0.12	-9999	-0.38	35	35
PXN	0.018	0.011	-9999	-0.11	4	4
HRAS/GTP	-0.062	0.11	-9999	-0.31	64	64
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.05	0.16	-9999	-0.41	67	67
VHL	0	0	-9999	-10000	0	0
ITGB3	0.019	0.008	-9999	-0.11	2	2
NOS3	-0.032	0.14	-9999	-0.43	33	33
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.042	0.14	-9999	-0.35	53	53
RAC1	0.015	0.035	-9999	-0.29	7	7
PRKCA	-0.036	0.12	-9999	-0.31	56	56
PRKCB	-0.042	0.12	-9999	-0.32	56	56
VCL	0.017	0.023	-9999	-0.29	3	3
VEGFA165/NRP1	-0.045	0.13	-9999	-0.34	55	55
VEGFR1/2 heterodimer/VEGFA homodimer	-0.033	0.12	-9999	-0.31	47	47
VEGFA165/NRP2	-0.037	0.093	-9999	-0.19	125	125
MAPKKK cascade	-0.041	0.15	-9999	-0.39	64	64
NRP2	0.017	0.015	-9999	-0.11	7	7
VEGFC homodimer	0.01	0.033	-9999	-0.11	37	37
NCK1	0.014	0.036	-9999	-0.19	14	14
ROCK1	0.016	0.031	-9999	-0.26	6	6
FAK1/Paxillin	-0.045	0.17	-9999	-0.43	53	53
MAP3K13	-0.041	0.13	-9999	-0.34	53	53
PDPK1	-0.052	0.15	-9999	-0.33	83	83

×

Signaling events mediated by PTP1B

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
PDGFRB	0.011	0.043	-10000	0	-0.18	21	21
Jak2/Leptin Receptor	-0.002	0.063	-10000	0	-0.23	9	9
PTP1B/AKT1	-0.036	0.11	-10000	0	-0.26	67	67
FYN	-0.019	0.1	-10000	0	-0.28	68	68
p210 bcr-abl/PTP1B	-0.045	0.1	-10000	0	-0.27	62	62
EGFR	-0.082	0.12	-10000	0	-0.18	267	267
EGF/EGFR	-0.066	0.11	-10000	0	-0.28	77	77
CSF1	0.019	0	-10000	0	-10000	0	0
AKT1	0.005	0.064	-10000	0	-0.26	28	28
INSR	0.019	0.002	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.043	0.12	-10000	0	-0.28	78	78
Insulin Receptor/Insulin	-0.012	0.096	-10000	0	-0.27	41	41
HCK	-0.034	0.11	-10000	0	-0.21	121	121
CRK	0.009	0.053	-10000	0	-0.28	17	17
TYK2	-0.043	0.11	-10000	0	-0.29	62	62
EGF	0.01	0.026	-10000	0	-0.11	21	21
YES1	0.005	0.061	-10000	0	-0.24	28	28
CAV1	-0.076	0.13	-10000	0	-0.3	90	90
TXN	0.006	0.051	-10000	0	-0.2	25	25
PTP1B/IRS1/GRB2	-0.035	0.11	-10000	0	-0.27	68	68
cell migration	0.045	0.1	0.27	62	-10000	0	62
STAT3	-0.003	0.08	-10000	0	-0.29	37	37
PRLR	0.023	0	-10000	0	-10000	0	0
ITGA2B	0.018	0.001	-10000	0	-10000	0	0
CSF1R	-0.042	0.11	-10000	0	-0.22	131	131
Prolactin Receptor/Prolactin	0.035	0.014	-10000	0	-10000	0	0
FGR	0.005	0.048	-10000	0	-0.29	7	7
PTP1B/p130 Cas	-0.043	0.097	-10000	0	-0.26	63	63
Crk/p130 Cas	-0.037	0.1	-10000	0	-0.25	70	70
DOK1	-0.029	0.099	-10000	0	-0.29	43	43
JAK2	-0.007	0.061	-10000	0	-0.23	9	9
Jak2/Leptin Receptor/Leptin	-0.011	0.11	-10000	0	-0.26	53	53
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
PTPN1	-0.045	0.1	-10000	0	-0.27	62	62
LYN	-0.018	0.097	-10000	0	-0.25	72	72
CDH2	-0.006	0.082	-10000	0	-0.26	46	46
SRC	-0.008	0.09	-10000	0	-0.56	11	11
ITGB3	0.018	0.008	-10000	0	-0.11	2	2
CAT1/PTP1B	-0.07	0.17	-10000	0	-0.38	93	93
CAPN1	0.017	0.006	-10000	0	-0.11	1	1
CSK	0.013	0.044	-10000	0	-0.29	11	11
PI3K	-0.026	0.12	-10000	0	-0.29	65	65
mol:H2O2	-0.001	0.003	-10000	0	-10000	0	0
STAT3 (dimer)	-0.007	0.099	-10000	0	-0.25	52	52
negative regulation of transcription	-0.007	0.06	-10000	0	-0.23	9	9
FCGR2A	-0.032	0.1	-10000	0	-0.21	115	115
FER	0.014	0.018	-10000	0	-0.11	10	10
alphaIIb/beta3 Integrin	0.025	0.006	-10000	0	-10000	0	0
BLK	0.018	0.011	-10000	0	-0.11	4	4
Insulin Receptor/Insulin/Shc	0.029	0.033	-10000	0	-0.16	9	9
RHOA	0.013	0.036	-10000	0	-0.3	7	7
LEPR	0.016	0.019	-10000	0	-0.11	11	11
BCAR1	0	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.014	0.039	-10000	0	-0.26	10	10
mol:NADPH	-0.002	0.002	-10000	0	-10000	0	0
TRPV6	-0.047	0.16	-10000	0	-0.39	77	77
PRL	0.02	0.019	-10000	0	-10000	0	0
SOCS3	0.012	0.012	-10000	0	-10000	0	0
SPRY2	-0.051	0.13	-10000	0	-0.27	127	127
Insulin Receptor/Insulin/IRS1	0.024	0.044	-10000	0	-0.15	25	25
CSF1/CSF1R	-0.05	0.12	-10000	0	-0.28	79	79
Ras protein signal transduction	0.018	0.038	0.11	12	-0.18	9	21
IRS1	-0.003	0.071	-10000	0	-0.19	54	54
INS	0.019	0.002	-10000	0	-10000	0	0
LEP	0.019	0.001	-10000	0	-10000	0	0
STAT5B	-0.025	0.085	-10000	0	-0.24	42	42
STAT5A	-0.025	0.085	-10000	0	-0.24	42	42
GRB2	0.014	0.039	-10000	0	-0.26	10	10
PDGFB-D/PDGFRB	-0.037	0.1	-10000	0	-0.26	65	65
CSN2	0.034	0.02	-10000	0	-10000	0	0
PIK3CA	-0.011	0.085	-10000	0	-0.22	65	65
LAT	-0.063	0.18	-10000	0	-0.52	66	66
YBX1	0.017	0.061	-10000	0	-0.31	17	17
LCK	0.017	0.016	-10000	0	-0.11	8	8
SHC1	0.004	0.052	-10000	0	-0.14	48	48
NOX4	-0.015	0.086	-10000	0	-0.2	78	78

×

TCGA08_rtk_signaling

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
PDGFRA	-0.042	0.11	-10000	0	-0.29	71	71
HRAS	0.009	0.055	-10000	0	-0.28	18	18
EGFR	-0.08	0.12	-10000	0	-0.18	267	267
AKT	0.019	0.026	0.13	3	-0.12	4	7
FOXO3	0.002	0.07	-10000	0	-0.27	32	32
AKT1	0.005	0.063	-10000	0	-0.25	28	28
FOXO1	-0.012	0.088	-10000	0	-0.23	67	67
AKT3	0.018	0.011	-10000	0	-0.11	4	4
FOXO4	0.019	0	-10000	0	-10000	0	0
MET	0.007	0.037	-10000	0	-0.11	47	47
PIK3CA	-0.011	0.085	-10000	0	-0.22	65	65
PIK3CB	0.018	0.013	-10000	0	-0.11	5	5
NRAS	-0.01	0.086	-10000	0	-0.29	42	42
PIK3CG	0.019	0	-10000	0	-10000	0	0
PIK3R3	0.017	0.015	-10000	0	-0.11	7	7
PIK3R2	0.018	0.01	-10000	0	-0.11	3	3
NF1	0.019	0	-10000	0	-10000	0	0
RAS	-0.049	0.085	-10000	0	-0.17	130	130
ERBB2	0.019	0.008	-10000	0	-0.11	2	2
proliferation/survival/translation	-0.015	0.085	0.33	23	-0.16	3	26
PI3K	-0.021	0.069	0.13	3	-0.13	120	123
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
KRAS	0.011	0.048	-10000	0	-0.28	14	14
FOXO	0.028	0.028	0.14	3	-0.049	4	7
AKT2	0.019	0	-10000	0	-10000	0	0
PTEN	0.013	0.037	-10000	0	-0.18	16	16

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.009	0.26	-10000	0	-0.74	34	34
CRP	-0.008	0.26	-10000	0	-0.76	32	32
cell cycle arrest	-0.025	0.3	-10000	0	-0.75	55	55
TIMP1	-0.084	0.36	-10000	0	-0.82	89	89
IL6ST	0.003	0.075	-10000	0	-0.27	35	35
Rac1/GDP	0.031	0.11	0.23	8	-0.33	25	33
AP1	-0.032	0.22	-10000	0	-0.56	60	60
GAB2	-0.004	0.082	-10000	0	-0.27	44	44
TNFSF11	-0.008	0.26	-10000	0	-0.7	40	40
HSP90B1	-0.035	0.29	-10000	0	-1	38	38
GAB1	0.004	0.056	-10000	0	-0.15	50	50
MAPK14	0.033	0.075	-10000	0	-0.31	11	11
AKT1	-0.018	0.2	-10000	0	-0.5	53	53
FOXO1	-0.026	0.2	-10000	0	-0.5	56	56
MAP2K6	0.029	0.085	0.22	8	-0.27	23	31
mol:GTP	0	0.003	-10000	0	-10000	0	0
MAP2K4	0.029	0.14	-10000	0	-0.37	33	33
MITF	0.023	0.098	0.23	8	-0.29	27	35
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.007	0.059	-10000	0	-0.28	21	21
A2M	-0.072	0.32	-10000	0	-1.3	36	36
CEBPB	0.002	0.078	-10000	0	-0.22	51	51
GRB2/SOS1/GAB family/SHP2	-0.016	0.16	-10000	0	-0.47	47	47
STAT3	-0.03	0.32	-10000	0	-0.8	55	55
STAT1	0.011	0.066	-10000	0	-0.79	3	3
CEBPD	-0.042	0.34	-10000	0	-0.96	52	52
PIK3CA	-0.009	0.085	-10000	0	-0.22	65	65
PI3K	-0.013	0.093	-10000	0	-0.21	87	87
JUN	-0.002	0.077	-10000	0	-0.28	37	37
PIAS3/MITF	0.028	0.1	0.22	7	-0.27	31	38
MAPK11	0.034	0.075	-10000	0	-0.31	10	10
STAT3 (dimer)/FOXO1	-0.035	0.31	-10000	0	-0.68	78	78
GRB2/SOS1/GAB family	-0.006	0.13	-10000	0	-0.31	60	60
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.016	0.13	-10000	0	-0.28	70	70
GRB2	0.015	0.039	-10000	0	-0.25	10	10
JAK2	0.013	0.027	-10000	0	-0.11	23	23
LBP	-0.006	0.25	-10000	0	-0.65	44	44
PIK3R1	-0.014	0.095	-10000	0	-0.27	62	62
JAK1	0.003	0.073	-10000	0	-0.26	34	34
MYC	-0.068	0.37	-10000	0	-0.9	74	74
FGG	-0.009	0.26	-10000	0	-0.77	32	32
macrophage differentiation	-0.025	0.3	-10000	0	-0.75	55	55
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0.034	0.07	-10000	0	-0.19	31	31
JUNB	-0.026	0.29	-10000	0	-0.8	45	45
FOS	-0.046	0.12	-10000	0	-0.22	146	146
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	0.024	0.1	0.24	8	-0.3	26	34
STAT1/PIAS1	0.024	0.12	0.26	8	-0.32	29	37
GRB2/SOS1/GAB family/SHP2/PI3K	-0.02	0.19	-10000	0	-0.41	68	68
STAT3 (dimer)	-0.029	0.31	-10000	0	-0.79	55	55
PRKCD	0.026	0.18	-10000	0	-0.43	43	43
IL6R	0.021	0.007	-10000	0	-10000	0	0
SOCS3	0.035	0.069	-10000	0	-10000	0	0
gp130 (dimer)/JAK1/JAK1/LMO4	0.02	0.088	-10000	0	-0.21	54	54
Rac1/GTP	0.029	0.12	0.24	1	-0.34	26	27
HCK	-0.034	0.11	-10000	0	-0.21	121	121
MAPKKK cascade	-0.026	0.21	-10000	0	-0.64	46	46
bone resorption	-0.004	0.24	-10000	0	-0.66	40	40
IRF1	-0.023	0.29	-10000	0	-0.8	45	45
mol:GDP	0.026	0.1	0.24	8	-0.3	25	33
SOS1	0.001	0.004	-10000	0	-10000	0	0
VAV1	0.025	0.1	0.24	8	-0.3	25	33
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	0.026	0.089	-10000	0	-0.35	21	21
PTPN11	0.012	0.094	-10000	0	-0.84	6	6
IL6/IL6RA	0.014	0.038	-10000	0	-10000	0	0
gp130 (dimer)/TYK2/TYK2/LMO4	0.021	0.081	-10000	0	-0.22	46	46
gp130 (dimer)/JAK2/JAK2/LMO4	0.024	0.065	-10000	0	-0.19	38	38
IL6	-0.004	0.052	-10000	0	-0.12	17	17
PIAS3	0.014	0.033	-10000	0	-0.19	12	12
PTPRE	-0.016	0.085	-10000	0	-0.23	62	62
PIAS1	0.008	0.056	-10000	0	-0.29	18	18
RAC1	0.015	0.036	-10000	0	-0.29	7	7
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	0.021	0.08	0.2	14	-0.24	31	45
LMO4	0.014	0.052	-10000	0	-0.3	14	14
STAT3 (dimer)/PIAS3	-0.02	0.3	-10000	0	-0.74	55	55
MCL1	-0.012	0.18	-10000	0	-0.63	29	29

×

IGF1 pathway

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
NCK2	0.009	0.053	-10000	0	-0.28	17	17
PTK2	0.009	0.054	-10000	0	-0.27	18	18
CRKL	0.006	0.047	-10000	0	-0.14	38	38
GRB2/SOS1/SHC	0.014	0.039	-10000	0	-0.17	16	16
HRAS	0.009	0.055	-10000	0	-0.28	18	18
IRS1/Crk	0.007	0.055	-10000	0	-0.16	41	41
IGF-1R heterotetramer/IGF1/PTP1B	0.018	0.055	-10000	0	-0.17	33	33
AKT1	-0.014	0.089	-10000	0	-0.17	99	99
BAD	-0.011	0.087	-10000	0	-0.16	99	99
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.005	0.05	-10000	0	-0.14	40	40
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.01	0.052	-10000	0	-0.16	32	32
RAF1	-0.021	0.16	-10000	0	-0.51	38	38
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.014	0.052	-10000	0	-0.15	35	35
YWHAZ	0.014	0.037	-10000	0	-0.29	7	7
IGF-1R heterotetramer/IGF1/IRS1	0.006	0.053	-10000	0	-0.13	55	55
PIK3CA	-0.011	0.085	-10000	0	-0.22	65	65
RPS6KB1	-0.009	0.074	-10000	0	-0.14	99	99
GNB2L1	0.018	0.019	-10000	0	-0.29	2	2
positive regulation of MAPKKK cascade	-0.018	0.12	0.2	2	-0.4	38	40
PXN	0.018	0.011	-10000	0	-0.11	4	4
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.011	0.026	-10000	0	-0.17	10	10
HRAS/GTP	-0.02	0.049	-10000	0	-0.15	54	54
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.021	0.054	-10000	0	-0.13	43	43
IGF-1R heterotetramer	0.009	0.048	-10000	0	-0.17	28	28
IGF-1R heterotetramer/IGF1/IRS/Nck	0.013	0.06	-10000	0	-0.17	41	41
Crk/p130 Cas/Paxillin	0.015	0.053	-10000	0	-0.14	41	41
IGF1R	0.009	0.048	-10000	0	-0.17	28	28
IGF1	0.011	0.029	-10000	0	-0.075	46	46
IRS2/Crk	-0.007	0.078	-10000	0	-0.17	82	82
PI3K	-0.004	0.089	-10000	0	-0.17	99	99
apoptosis	0.003	0.084	0.21	51	-10000	0	51
HRAS/GDP	0.007	0.037	-10000	0	-0.19	18	18
PRKCD	0.006	0.063	-10000	0	-0.22	31	31
RAF1/14-3-3 E	-0.009	0.14	-10000	0	-0.42	40	40
BAD/14-3-3	-0.003	0.088	-10000	0	-0.23	51	51
PRKCZ	-0.014	0.073	-10000	0	-0.15	99	99
Crk/p130 Cas/Paxillin/FAK1	-0.003	0.08	-10000	0	-0.2	53	53
PTPN1	0.013	0.042	-10000	0	-0.29	10	10
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.004	0.065	-10000	0	-0.23	30	30
BCAR1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.003	0.078	-10000	0	-0.15	84	84
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
IRS1/NCK2	0.007	0.058	-10000	0	-0.17	41	41
GRB10	-0.018	0.091	-10000	0	-0.2	89	89
PTPN11	0.006	0.048	-10000	0	-0.14	38	38
IRS1	0.003	0.049	-10000	0	-0.15	37	37
IRS2	-0.004	0.067	-10000	0	-0.18	52	52
IGF-1R heterotetramer/IGF1	0.008	0.058	-10000	0	-0.18	38	38
GRB2	0.014	0.039	-10000	0	-0.26	10	10
PDPK1	-0.011	0.078	-10000	0	-0.16	99	99
YWHAE	0.011	0.045	-10000	0	-0.21	19	19
PRKD1	-0.001	0.078	-10000	0	-0.23	46	46
SHC1	0.004	0.052	-10000	0	-0.14	48	48

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	0.025	0.006	-10000	0	-10000	0	0
NFATC2	0.016	0.16	-10000	0	-0.44	32	32
NFATC3	-0.005	0.1	0.29	12	-0.23	67	79
CD40LG	-0.079	0.3	-10000	0	-0.73	73	73
ITCH	0.019	0.047	-10000	0	-0.2	7	7
CBLB	0.019	0.046	-10000	0	-0.2	7	7
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.013	0.2	-10000	0	-0.51	41	41
JUNB	-0.003	0.067	-10000	0	-0.17	63	63
CaM/Ca2+/Calcineurin A alpha-beta B1	0.018	0.057	-10000	0	-0.21	16	16
T cell anergy	0.006	0.06	-10000	0	-0.28	9	9
TLE4	0.023	0.11	-10000	0	-0.3	30	30
Jun/NFAT1-c-4/p21SNFT	-0.051	0.31	-10000	0	-0.73	78	78
AP-1/NFAT1-c-4	-0.063	0.36	-10000	0	-0.83	73	73
IKZF1	0.024	0.1	-10000	0	-0.32	19	19
T-helper 2 cell differentiation	0.006	0.14	-10000	0	-0.53	11	11
AP-1/NFAT1	-0.005	0.16	-10000	0	-0.33	73	73
CALM1	0.014	0.051	-10000	0	-0.23	16	16
EGR2	-0.087	0.42	0.5	2	-1	77	79
EGR3	-0.094	0.42	-10000	0	-1.1	67	67
NFAT1/FOXP3	0.037	0.11	-10000	0	-0.29	32	32
EGR1	-0.031	0.11	-10000	0	-0.29	74	74
JUN	-0.001	0.073	-10000	0	-0.28	32	32
EGR4	0.019	0.013	-10000	0	-0.11	5	5
mol:Ca2+	0.003	0.02	-10000	0	-10000	0	0
GBP3	0.011	0.1	0.2	2	-0.3	32	34
FOSL1	0.007	0.038	-10000	0	-0.11	51	51
NFAT1-c-4/MAF/IRF4	-0.029	0.31	-10000	0	-0.71	78	78
DGKA	0.023	0.1	-10000	0	-0.32	18	18
CREM	0.017	0.014	-10000	0	-0.11	6	6
NFAT1-c-4/PPARG	-0.042	0.31	-10000	0	-0.74	78	78
CTLA4	0.027	0.084	-10000	0	-0.24	25	25
NFAT1-c-4 (dimer)/EGR1	-0.057	0.33	-10000	0	-0.8	78	78
NFAT1-c-4 (dimer)/EGR4	-0.033	0.31	-10000	0	-0.73	78	78
FOS	-0.041	0.11	-10000	0	-0.21	133	133
IFNG	0.011	0.13	-10000	0	-0.43	11	11
T cell activation	-0.034	0.2	-10000	0	-0.6	37	37
MAF	0.008	0.058	-10000	0	-0.27	21	21
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.032	0.25	0.6	74	-0.49	4	78
TNF	-0.055	0.3	-10000	0	-0.71	78	78
FASLG	-0.1	0.43	-10000	0	-1.1	79	79
TBX21	0.025	0.007	-10000	0	-10000	0	0
BATF3	0	0	-10000	0	-10000	0	0
PRKCQ	0.018	0.024	-10000	0	-0.11	3	3
PTPN1	0.018	0.13	-10000	0	-0.42	24	24
NFAT1-c-4/ICER1	-0.043	0.31	-10000	0	-0.73	78	78
GATA3	0.02	0.018	-10000	0	-0.11	10	10
T-helper 1 cell differentiation	0.011	0.13	-10000	0	-0.43	11	11
IL2RA	-0.017	0.2	-10000	0	-0.49	51	51
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	0.013	0.13	-10000	0	-0.38	40	40
E2F1	0.012	0.045	-10000	0	-0.22	15	15
PPARG	0.015	0.024	-10000	0	-0.11	18	18
SLC3A2	0.01	0.14	-10000	0	-0.42	40	40
IRF4	0.019	0.006	-10000	0	-0.11	1	1
PTGS2	-0.088	0.3	-10000	0	-0.73	73	73
CSF2	-0.079	0.3	-10000	0	-0.73	73	73
JunB/Fra1/NFAT1-c-4	-0.041	0.31	-10000	0	-0.72	78	78
IL4	0.005	0.15	-10000	0	-0.55	11	11
IL5	-0.08	0.3	-10000	0	-0.73	73	73
IL2	-0.035	0.2	-10000	0	-0.61	37	37
IL3	-0.006	0.06	-10000	0	-0.64	2	2
RNF128	0.005	0.065	-10000	0	-0.26	7	7
NFATC1	-0.033	0.25	0.49	4	-0.6	72	76
CDK4	-0.013	0.26	0.53	16	-1.1	15	31
PTPRK	-0.002	0.17	-10000	0	-0.5	46	46
IL8	-0.12	0.32	-10000	0	-0.77	78	78
POU2F1	0.022	0.028	-10000	0	-0.29	2	2

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	-0.005	0.082	-9999	-0.27	44	44
ELF1	0.016	0.051	-9999	-0.28	12	12
CCNA2	-0.027	0.095	-9999	-0.19	117	117
PIK3CA	-0.01	0.085	-9999	-0.22	65	65
JAK3	0.019	0.002	-9999	-10000	0	0
PIK3R1	-0.014	0.095	-9999	-0.27	62	62
JAK1	0.002	0.071	-9999	-0.26	34	34
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.006	0.2	-9999	-0.53	47	47
SHC1	0.004	0.052	-9999	-0.14	48	48
SP1	-0.034	0.12	-9999	-0.28	99	99
IL2RA	0.022	0.035	-9999	-0.18	3	3
IL2RB	0.015	0.024	-9999	-0.11	19	19
SOS1	0	0.002	-9999	-10000	0	0
IL2RG	0.013	0.027	-9999	-0.11	24	24
G1/S transition of mitotic cell cycle	-0.12	0.28	-9999	-0.56	135	135
PTPN11	0.016	0.033	-9999	-0.27	7	7
CCND2	-0.088	0.22	-9999	-0.55	99	99
LCK	0.017	0.016	-9999	-0.11	8	8
GRB2	0.014	0.039	-9999	-0.26	10	10
IL2	0.019	0.006	-9999	-0.11	1	1
CDK6	0.019	0	-9999	-10000	0	0
CCND3	-0.006	0.21	-9999	-0.75	30	30

×

TCGA08_retinoblastoma

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
CDKN2B	0.011	0.019	-10000	0	-10000	0	0
CDKN2C	-0.011	0.09	-10000	0	-0.26	60	60
CDKN2A	-0.016	0.058	-10000	0	-0.11	108	108
CCND2	0.002	0.033	0.13	27	-0.099	2	29
RB1	-0.002	0.036	-10000	0	-0.14	27	27
CDK4	0.003	0.039	0.15	27	-0.13	3	30
CDK6	0.005	0.037	0.15	27	-10000	0	27
G1/S progression	0	0.042	0.14	35	-10000	0	35

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.014	0.049	-9999	-0.19	25	25
VLDLR	-0.02	0.092	-9999	-0.2	96	96
CRKL	0.018	0.01	-9999	-0.11	3	3
LRPAP1	0.013	0.043	-9999	-0.28	11	11
FYN	-0.019	0.1	-9999	-0.28	68	68
ITGA3	0.005	0.042	-9999	-0.11	57	57
RELN/VLDLR/Fyn	-0.015	0.085	-9999	-0.17	107	107
MAPK8IP1/MKK7/MAP3K11/JNK1	0.051	0.028	-9999	-0.14	7	7
AKT1	-0.03	0.11	-9999	-0.2	121	121
MAP2K7	0.019	0	-9999	-10000	0	0
RAPGEF1	0.019	0	-9999	-10000	0	0
DAB1	0.019	0.006	-9999	-0.11	1	1
RELN/LRP8/DAB1	0.024	0.033	-9999	-0.12	11	11
LRPAP1/LRP8	0.017	0.044	-9999	-0.2	16	16
RELN/LRP8/DAB1/Fyn	0.013	0.066	-9999	-0.14	67	67
DAB1/alpha3/beta1 Integrin	0.015	0.054	-9999	-0.16	15	15
long-term memory	0.024	0.066	-9999	-0.13	63	63
DAB1/LIS1	0.015	0.071	-9999	-0.14	68	68
DAB1/CRLK/C3G	0.019	0.052	-9999	-0.17	11	11
PIK3CA	-0.011	0.085	-9999	-0.22	65	65
DAB1/NCK2	0.016	0.071	-9999	-0.14	69	69
ARHGEF2	0.014	0.034	-9999	-0.18	13	13
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	0.017	0.016	-9999	-0.11	8	8
CDK5R1	0.014	0.025	-9999	-0.11	21	21
RELN	0.007	0.038	-9999	-0.11	50	50
PIK3R1	-0.015	0.095	-9999	-0.27	62	62
RELN/LRP8/Fyn	0.003	0.075	-9999	-0.18	67	67
GRIN2A/RELN/LRP8/DAB1/Fyn	0.022	0.069	-9999	-0.14	63	63
MAPK8	0.019	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	0.008	0.055	-9999	-0.13	53	53
ITGB1	0.019	0	-9999	-10000	0	0
MAP1B	-0.005	0.067	-9999	-0.16	67	67
RELN/LRP8	0.021	0.045	-9999	-0.15	21	21
GRIN2B/RELN/LRP8/DAB1/Fyn	0.023	0.069	-9999	-0.14	63	63
PI3K	-0.015	0.092	-9999	-0.21	87	87
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	0.018	0.03	-9999	-0.19	1	1
RAP1A	0.013	0.05	-9999	-0.16	12	12
PAFAH1B1	0.009	0.055	-9999	-0.28	18	18
MAPK8IP1	0.016	0.019	-9999	-0.11	11	11
CRLK/C3G	0.028	0.007	-9999	-10000	0	0
GRIN2B	0.019	0	-9999	-10000	0	0
NCK2	0.009	0.053	-9999	-0.28	17	17
neuron differentiation	0.015	0.068	-9999	-0.28	13	13
neuron adhesion	0.017	0.049	-9999	-0.15	14	14
LRP8	0.009	0.043	-9999	-0.16	29	29
GSK3B	-0.03	0.12	-9999	-0.21	121	121
RELN/VLDLR/DAB1/Fyn	-0.003	0.075	-9999	-0.14	108	108
MAP3K11	0.017	0.021	-9999	-0.18	5	5
RELN/VLDLR/DAB1/P13K	-0.029	0.1	-9999	-0.2	121	121
CDK5	0.004	0.064	-9999	-0.24	31	31
MAPT	-0.028	0.088	-9999	-0.24	70	70
neuron migration	-0.022	0.12	-9999	-0.28	71	71
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	0.015	0.068	-9999	-0.29	13	13
RELN/VLDLR	0.01	0.067	-9999	-0.14	66	66

×

Class I PI3K signaling events

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	0.002	0.064	0.18	6	-0.27	15	21
DAPP1	-0.031	0.13	-10000	0	-0.32	69	69
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.058	0.21	-10000	0	-0.48	81	81
mol:DAG	-0.014	0.096	0.17	3	-0.2	84	87
HRAS	0.013	0.04	-10000	0	-0.28	9	9
RAP1A	0.017	0.015	-10000	0	-0.3	1	1
ARF5/GDP	-0.008	0.11	-10000	0	-0.26	65	65
PLCG2	-0.002	0.069	-10000	0	-0.19	52	52
PLCG1	0.017	0.025	-10000	0	-0.22	5	5
ARF5	0.014	0.04	-10000	0	-0.29	9	9
mol:GTP	-0.015	0.056	0.18	6	-0.15	58	64
ARF1/GTP	-0.006	0.06	0.17	6	-0.16	58	64
RHOA	0.015	0.035	-10000	0	-0.29	7	7
YES1	0.005	0.061	-10000	0	-0.24	28	28
RAP1A/GTP	0	0.06	0.18	6	-0.15	59	65
ADAP1	-0.006	0.056	0.17	6	-0.14	59	65
ARAP3	-0.015	0.055	0.18	6	-0.15	58	64
INPPL1	0.016	0.033	-10000	0	-0.29	6	6
PREX1	0	0	-10000	0	-10000	0	0
ARHGEF6	-0.008	0.088	-10000	0	-0.28	48	48
ARHGEF7	0	0.071	-10000	0	-0.25	37	37
ARF1	0.014	0.036	-10000	0	-0.25	9	9
NRAS	0.008	0.049	-10000	0	-0.18	27	27
FYN	-0.019	0.1	-10000	0	-0.28	68	68
ARF6	0.018	0.015	-10000	0	-0.2	2	2
FGR	0.005	0.048	-10000	0	-0.29	7	7
mol:Ca2+	-0.002	0.05	-10000	0	-0.1	80	80
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.002	0.066	-10000	0	-0.23	36	36
ZAP70	0.019	0.006	-10000	0	-0.11	1	1
mol:IP3	-0.006	0.069	-10000	0	-0.14	80	80
LYN	-0.018	0.097	-10000	0	-0.25	72	72
ARF1/GDP	-0.008	0.11	-10000	0	-0.26	63	63
RhoA/GDP	0	0.083	0.18	4	-0.26	33	37
PDK1/Src/Hsp90	0.038	0.012	-10000	0	-0.15	2	2
BLNK	-0.036	0.1	-10000	0	-0.2	130	130
actin cytoskeleton reorganization	-0.005	0.1	0.18	4	-0.3	37	41
SRC	0.019	0	-10000	0	-10000	0	0
PLEKHA2	0.011	0.015	-10000	0	-0.051	29	29
RAC1	0.015	0.035	-10000	0	-0.29	7	7
PTEN	0.013	0.035	-10000	0	-0.17	16	16
HSP90AA1	0.018	0.019	-10000	0	-0.29	2	2
ARF6/GTP	0.004	0.059	0.18	6	-0.14	58	64
RhoA/GTP	0.003	0.062	0.18	6	-0.25	15	21
Src family/SYK family/BLNK-LAT	-0.057	0.2	-10000	0	-0.46	80	80
BLK	0.018	0.011	-10000	0	-0.11	4	4
PDPK1	0.019	0	-10000	0	-10000	0	0
CYTH1	-0.006	0.056	0.17	6	-0.14	59	65
HCK	-0.034	0.11	-10000	0	-0.21	121	121
CYTH3	-0.006	0.056	0.17	6	-0.14	59	65
CYTH2	-0.006	0.056	0.17	6	-0.14	59	65
KRAS	0.013	0.04	-10000	0	-0.28	9	9
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.01	0.052	0.14	5	-0.22	13	18
SGK1	0.01	0.04	-10000	0	-0.16	14	14
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	-0.018	0.11	-10000	0	-0.27	62	62
SOS1	0	0	-10000	0	-10000	0	0
SYK	-0.005	0.072	-10000	0	-0.18	62	62
ARF6/GDP	-0.003	0.079	0.16	6	-0.24	35	41
mol:PI-3-4-5-P3	-0.006	0.059	0.18	6	-0.15	59	65
ARAP3/RAP1A/GTP	0	0.06	0.18	6	-0.15	59	65
VAV1	0.016	0.019	-10000	0	-0.11	12	12
mol:PI-3-4-P2	0.008	0.022	-10000	0	-0.2	6	6
RAS family/GTP/PI3K Class I	0.012	0.065	0.18	6	-0.15	59	65
PLEKHA1	0.01	0.022	-10000	0	-0.069	27	27
Rac1/GDP	-0.008	0.12	-10000	0	-0.27	62	62
LAT	0.018	0.014	-10000	0	-0.11	6	6
Rac1/GTP	-0.02	0.16	-10000	0	-0.42	54	54
ITK	-0.001	0.057	0.18	6	-0.14	58	64
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.026	0.13	0.19	3	-0.28	84	87
LCK	0.017	0.016	-10000	0	-0.11	8	8
BTK	-0.001	0.057	0.18	6	-0.14	58	64

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	-0.022	0.079	-10000	0	-0.19	87	87
MAP4K4	0.015	0.061	-10000	0	-0.25	13	13
BAG4	0.018	0.011	-10000	0	-0.11	4	4
PKC zeta/ceramide	0.011	0.03	0.075	87	-10000	0	87
NFKBIA	0.002	0.066	-10000	0	-0.24	34	34
BIRC3	-0.001	0.048	-10000	0	-0.11	78	78
BAX	0.011	0.042	-10000	0	-0.38	5	5
RIPK1	0.016	0.019	-10000	0	-0.11	11	11
AKT1	-0.004	0.058	-10000	0	-0.24	28	28
BAD	0.014	0.036	0.085	85	-0.14	5	90
SMPD1	0.008	0.044	-10000	0	-0.15	13	13
RB1	0.015	0.034	0.085	85	-0.14	2	87
FADD/Caspase 8	0.028	0.051	-10000	0	-0.2	5	5
MAP2K4	0.017	0.035	0.085	81	-0.12	4	85
NSMAF	0.006	0.062	-10000	0	-0.28	24	24
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.016	0.037	0.085	80	-0.13	11	91
EGF	0.014	0.025	-10000	0	-0.11	21	21
mol:ceramide	0.013	0.035	0.087	87	-10000	0	87
MADD	0.018	0.015	-10000	0	-0.2	2	2
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.021	0.078	-10000	0	-0.19	84	84
ASAH1	0.017	0.023	-10000	0	-0.29	3	3
negative regulation of cell cycle	0.015	0.034	0.085	85	-0.14	2	87
cell proliferation	0.034	0.038	-10000	0	-0.095	14	14
BID	-0.006	0.15	-10000	0	-0.61	27	27
MAP3K1	0.015	0.034	0.085	86	-0.069	1	87
EIF2A	0.014	0.037	0.082	82	-0.12	14	96
TRADD	0.019	0	-10000	0	-10000	0	0
CRADD	0.017	0.015	-10000	0	-0.11	7	7
MAPK3	0.022	0.037	0.09	14	-0.11	14	28
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.019	0.048	0.089	74	-0.17	18	92
Cathepsin D/ceramide	0.019	0.034	0.088	78	-0.051	29	107
FADD	0.021	0.05	-10000	0	-0.17	10	10
KSR1	0.016	0.032	0.085	87	-10000	0	87
MAPK8	0.02	0.032	0.09	2	-10000	0	2
PRKRA	0.012	0.04	0.085	82	-0.14	14	96
PDGFA	-0.045	0.12	-10000	0	-0.22	141	141
TRAF2	0.019	0	-10000	0	-10000	0	0
IGF1	0.014	0.025	-10000	0	-0.11	21	21
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	0.013	0.035	0.087	87	-10000	0	87
CTSD	0.005	0.053	-10000	0	-0.16	43	43
regulation of nitric oxide biosynthetic process	0.023	0.03	-10000	0	-0.19	9	9
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	0.037	0.04	-10000	0	-0.1	14	14
PRKCD	0.012	0.029	-10000	0	-0.11	27	27
PRKCZ	0	0	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.021	0.078	-10000	0	-0.19	84	84
RelA/NF kappa B1	0.024	0.03	-10000	0	-0.19	9	9
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.019	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.019	0.053	-10000	0	-0.18	9	9
TNFR1A/BAG4/TNF-alpha	0.02	0.057	-10000	0	-0.15	50	50
mol:Sphingosine-1-phosphate	-0.022	0.078	-10000	0	-0.19	87	87
MAP2K1	0.017	0.039	0.086	77	-0.12	16	93
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.018	0.02	-10000	0	-0.23	3	3
CYCS	0.011	0.033	-10000	0	-0.16	9	9
TNFRSF1A	-0.01	0.091	-10000	0	-0.29	50	50
NFKB1	0.014	0.038	-10000	0	-0.22	12	12
TNFR1A/BAG4	0.007	0.065	-10000	0	-0.19	50	50
EIF2AK2	0.015	0.039	0.085	82	-0.12	14	96
TNF-alpha/TNFR1A/FAN	0.013	0.071	-10000	0	-0.17	65	65
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.027	0.046	-10000	0	-0.33	2	2
MAP2K2	0.019	0.037	0.086	78	-0.12	12	90
SMPD3	0.011	0.047	-10000	0	-0.15	16	16
TNF	0.018	0.01	-10000	0	-0.11	3	3
PKC zeta/PAR4	0.014	0	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	0.01	0.033	0.088	52	-10000	0	52
NF kappa B1/RelA/I kappa B alpha	0.033	0.044	-10000	0	-0.13	30	30
AIFM1	0.01	0.034	-10000	0	-0.18	7	7
BCL2	0.019	0	-10000	0	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

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
ERK1-2/ELK1	-0.015	0.14	-9999	-0.29	89	89
MAP3K8	0.003	0.042	-9999	-0.11	62	62
FOS	-0.006	0.095	-9999	-0.35	19	19
PRKCA	0.016	0.008	-9999	-10000	0	0
PTPN7	0.014	0.017	-9999	-0.12	5	5
HRAS	0.008	0.055	-9999	-0.28	18	18
PRKCB	-0.002	0.006	-9999	-0.011	144	144
NRAS	-0.01	0.086	-9999	-0.28	45	45
RAS family/GTP	0.008	0.069	-9999	-0.17	59	59
MAPK3	0.012	0.041	-9999	-10000	0	0
MAP2K1	0.001	0.057	-9999	-0.24	17	17
ELK1	0.014	0.013	-9999	-0.11	1	1
BRAF	0.008	0.025	-9999	-10000	0	0
mol:GTP	-0.001	0.002	-9999	-0.003	139	139
MAPK1	-0.002	0.1	-9999	-0.57	13	13
RAF1	-0.003	0.077	-9999	-0.39	18	18
KRAS	0.011	0.048	-9999	-0.28	14	14

×

Signaling events mediated by HDAC Class III

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
EP300	0.012	0.046	-10000	0	-0.24	15	15
HDAC4	0.007	0.056	-10000	0	-0.22	27	27
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.015	0.043	0.2	5	-0.13	40	45
CDKN1A	-0.052	0.17	-10000	0	-0.51	62	62
KAT2B	0	0	-10000	0	-10000	0	0
BAX	0.014	0.035	-10000	0	-0.29	5	5
FOXO3	-0.007	0.043	0.29	5	-0.16	18	23
FOXO1	-0.012	0.088	-10000	0	-0.23	67	67
FOXO4	0.017	0.032	-10000	0	-0.2	11	11
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.018	0.019	-10000	0	-0.29	2	2
TAT	0.019	0	-10000	0	-10000	0	0
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.01	0	-10000	0	-10000	0	0
PPARGC1A	-0.006	0.067	-10000	0	-0.15	76	76
FHL2	-0.027	0.088	-10000	0	-0.16	134	134
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.031	0.046	0.14	40	-0.22	6	46
HIST2H4A	0.015	0.043	0.13	40	-0.2	5	45
SIRT1/FOXO3a	0.013	0.05	0.14	43	-0.12	18	61
SIRT1	0.025	0.061	0.18	40	-0.16	19	59
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.035	0.053	0.14	34	-0.16	21	55
SIRT1/Histone H1b	0.03	0.049	0.15	37	-0.19	10	47
apoptosis	-0.037	0.046	0.17	10	-0.14	38	48
SIRT1/PGC1A	0.015	0.052	0.13	31	-0.15	21	52
p53/SIRT1	0.031	0.11	0.34	47	-0.19	27	74
SIRT1/FOXO4	0.031	0.048	0.15	39	-0.18	10	49
FOXO1/FHL2/SIRT1	-0.003	0.072	0.14	17	-0.15	69	86
HIST1H1E	0.015	0.033	-10000	0	-0.2	11	11
SIRT1/p300	0.027	0.055	0.14	39	-0.2	16	55
muscle cell differentiation	-0.022	0.038	0.16	5	-0.13	40	45
TP53	0.012	0.082	0.18	44	-0.2	42	86
KU70/SIRT1/BAX	0.038	0.047	0.14	38	-0.17	10	48
CREBBP	0.019	0	-10000	0	-10000	0	0
MEF2D	0.019	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.032	0.043	0.14	40	-0.19	5	45
ACSS2	0.015	0.043	0.13	40	-0.2	5	45
SIRT1/PCAF/MYOD	0.022	0.038	0.13	40	-0.16	5	45

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.011	0.024	-9999	-0.2	7	7
PRKCZ	0	0	-9999	-10000	0	0
MAP3K7IP2	0.008	0.057	-9999	-0.27	20	20
ERC1	-0.002	0.074	-9999	-0.24	43	43
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.032	0.12	-9999	-0.31	69	69
IRAK/TOLLIP	0.019	0.038	-9999	-0.15	23	23
IKBKB	0.019	0	-9999	-10000	0	0
IKBKG	0.019	0	-9999	-10000	0	0
IL1 alpha/IL1R2	0.009	0.039	-9999	-0.14	6	6
IL1A	0.013	0.027	-9999	-0.11	23	23
IL1B	-0.027	0.075	-9999	-0.18	83	83
IRAK/TRAF6/p62/Atypical PKCs	0.027	0.053	-9999	-0.15	38	38
IL1R2	-0.003	0.049	-9999	-0.11	91	91
IL1R1	0.016	0.02	-9999	-0.11	13	13
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.023	0.1	-9999	-0.34	37	37
TOLLIP	0.016	0.021	-9999	-0.11	14	14
TICAM2	0	0	-9999	-10000	0	0
MAP3K3	0.019	0.006	-9999	-0.11	1	1
TAK1/TAB1/TAB2	0.025	0.055	-9999	-0.18	31	31
IKK complex/ELKS	0.027	0.089	-9999	-0.29	32	32
JUN	0.021	0.05	-9999	-0.23	15	15
MAP3K7	0.006	0.059	-9999	-0.24	26	26
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.034	0.1	-9999	-0.22	83	83
IL1 alpha/IL1R1/IL1RAP/MYD88	0.015	0.069	-9999	-0.15	61	61
PIK3R1	-0.015	0.095	-9999	-0.27	62	62
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.023	0.067	-9999	-0.14	61	61
IL1 beta fragment/IL1R1/IL1RAP	-0.023	0.085	-9999	-0.17	107	107
NFKB1	0.014	0.038	-9999	-0.22	12	12
MAPK8	0.023	0.045	-9999	-0.23	10	10
IRAK1	0.015	0.027	-9999	-0.2	7	7
IL1RN/IL1R1	0.025	0.016	-9999	-10000	0	0
IRAK4	0.019	0.008	-9999	-0.11	2	2
PRKCI	0.015	0.028	-9999	-0.14	15	15
TRAF6	0.018	0.019	-9999	-0.29	2	2
PI3K	-0.015	0.092	-9999	-0.21	87	87
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.027	0.12	-9999	-0.3	69	69
CHUK	0.016	0.024	-9999	-0.15	9	9
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.023	0.085	-9999	-0.17	107	107
IL1 beta/IL1R2	-0.029	0.078	-9999	-0.15	118	118
IRAK/TRAF6/TAK1/TAB1/TAB2	0.035	0.063	-9999	-0.27	12	12
NF kappa B1 p50/RelA	-0.028	0.095	-9999	-0.2	86	86
IRAK3	0.018	0.014	-9999	-0.11	6	6
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.013	0.079	-9999	-0.14	107	107
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.004	0.076	-9999	-0.18	61	61
IL1 alpha/IL1R1/IL1RAP	0.014	0.055	-9999	-0.14	43	43
RELA	0.018	0.02	-9999	-0.23	3	3
MAP3K7IP1	0.019	0	-9999	-10000	0	0
SQSTM1	0.004	0.062	-9999	-0.29	20	20
MYD88	0	0.075	-9999	-0.29	33	33
IRAK/TRAF6/MEKK3	0.032	0.038	-9999	-0.13	25	25
IL1RAP	-0.012	0.084	-9999	-0.2	76	76
UBE2N	0.015	0.035	-9999	-0.29	7	7
IRAK/TRAF6	-0.03	0.06	-9999	-0.19	43	43
CASP1	-0.033	0.11	-9999	-0.29	75	75
IL1RN/IL1R2	0.012	0.036	-9999	-0.14	3	3
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.021	0.097	-9999	-0.17	118	118
TMEM189-UBE2V1	0	0	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.002	0.099	-9999	-0.32	35	35
PIK3CA	-0.011	0.085	-9999	-0.22	65	65
IL1RN	0.018	0.011	-9999	-0.11	4	4
TRAF6/TAK1/TAB1/TAB2	0.033	0.054	-9999	-0.16	34	34
MAP2K6	0.021	0.048	-9999	-0.14	34	34

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	-0.045	0.095	-9999	-0.2	132	132
alphaV beta3 Integrin	0.025	0.049	-9999	-0.16	31	31
PTK2	-0.031	0.14	-9999	-0.32	59	59
IGF1R	-0.001	0.07	-9999	-0.21	46	46
PI4KB	0.018	0.016	-9999	-0.17	3	3
MFGE8	0.016	0.025	-9999	-0.15	10	10
SRC	0.019	0	-9999	-10000	0	0
CDKN1B	0.003	0.092	-9999	-0.36	29	29
VEGFA	-0.068	0.13	-9999	-0.22	188	188
ILK	0.013	0.07	-9999	-0.37	15	15
ROCK1	0.016	0.031	-9999	-0.26	6	6
AKT1	0.012	0.076	-9999	-0.38	17	17
PTK2B	-0.025	0.075	-9999	-0.14	136	136
alphaV/beta3 Integrin/JAM-A	0.03	0.054	-9999	-0.15	34	34
CBL	0.019	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.028	0.042	-9999	-0.15	25	25
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.02	0.065	-9999	-0.14	60	60
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.021	0.1	-9999	-0.32	29	29
alphaV/beta3 Integrin/Syndecan-1	0.017	0.052	-9999	-0.16	28	28
PI4KA	-0.007	0.083	-9999	-0.26	49	49
IGF-1R heterotetramer/IGF1/IRS1	0.009	0.076	-9999	-0.14	84	84
PI4 Kinase	0.01	0.06	-9999	-0.19	40	40
PIK3CA	-0.011	0.085	-9999	-0.22	65	65
alphaV/beta3 Integrin/Osteopontin	0.011	0.075	-9999	-0.18	63	63
RPS6KB1	0.005	0.071	-9999	-0.23	28	28
TLN1	-0.003	0.065	-9999	-0.16	64	64
MAPK3	0.008	0.1	-9999	-0.38	28	28
GPR124	0.014	0.024	-9999	-0.11	19	19
MAPK1	0.004	0.11	-9999	-0.4	29	29
PXN	0.018	0.011	-9999	-0.11	4	4
PIK3R1	-0.015	0.095	-9999	-0.27	62	62
alphaV/beta3 Integrin/Tumstatin	0.028	0.041	-9999	-0.15	25	25
cell adhesion	0.027	0.053	-9999	-0.17	33	33
ANGPTL3	0.019	0.006	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src	-0.025	0.083	-9999	-0.16	132	132
IGF-1R heterotetramer	-0.001	0.069	-9999	-0.21	46	46
Rac1/GDP	0.011	0.024	-9999	-0.2	7	7
TGFBR2	0.012	0.035	-9999	-0.15	21	21
ITGB3	0.019	0.008	-9999	-0.11	2	2
IGF1	0.014	0.025	-9999	-0.11	21	21
RAC1	0.015	0.035	-9999	-0.29	7	7
regulation of cell-matrix adhesion	0.025	0.043	-9999	-0.15	25	25
apoptosis	0.003	0.067	-9999	-0.25	32	32
CD47	0.012	0.043	-9999	-0.21	16	16
alphaV/beta3 Integrin/CD47	0.024	0.051	-9999	-0.16	32	32
VCL	0.017	0.023	-9999	-0.29	3	3
alphaV/beta3 Integrin/Del1	0.028	0.041	-9999	-0.15	25	25
CSF1	0.019	0	-9999	-10000	0	0
PIK3C2A	0.013	0.023	-9999	-0.13	4	4
PI4 Kinase/Pyk2	-0.035	0.069	-9999	-0.2	49	49
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.021	0.089	-9999	-0.15	136	136
FAK1/Vinculin	-0.016	0.12	-9999	-0.26	60	60
alphaV beta3/Integrin/ppsTEM5	0.025	0.044	-9999	-0.15	25	25
RHOA	0.015	0.035	-9999	-0.29	7	7
VTN	0.018	0.01	-9999	-0.11	3	3
BCAR1	0	0	-9999	-10000	0	0
FGF2	0.013	0.036	-9999	-0.16	19	19
F11R	0.008	0.043	-9999	-0.21	13	13
alphaV/beta3 Integrin/Lactadherin	0.027	0.045	-9999	-0.16	27	27
alphaV/beta3 Integrin/TGFBR2	0.024	0.047	-9999	-0.15	32	32
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.028	0.037	-9999	-0.14	25	25
HSP90AA1	0.018	0.019	-9999	-0.29	2	2
alphaV/beta3 Integrin/Talin	0.015	0.053	-9999	-0.14	44	44
mol:GDP	0	0	-9999	-10000	0	0
FN1	0.001	0.07	-9999	-0.26	34	34
alphaV/beta3 Integrin/Pyk2	-0.018	0.081	-9999	-0.14	136	136
SDC1	0	0.046	-9999	-0.11	76	76
VAV3	0.008	0.044	-9999	-0.16	25	25
PTPN11	0.015	0.033	-9999	-0.26	7	7
IRS1	-0.003	0.071	-9999	-0.19	54	54
FAK1/Paxillin	-0.016	0.12	-9999	-0.25	59	59
cell migration	-0.01	0.11	-9999	-0.25	51	51
ITGAV	0.003	0.067	-9999	-0.25	32	32
PI3K	0.012	0.09	-9999	-0.22	45	45
SPP1	-0.011	0.092	-9999	-0.29	51	51
KDR	0.001	0.057	-9999	-0.14	59	59
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.003	0.067	-9999	-0.25	32	32
COL4A3	0.019	0	-9999	-10000	0	0
angiogenesis	0.008	0.11	-9999	-0.42	28	28
Rac1/GTP	0.008	0.058	-9999	-0.13	65	65
EDIL3	0.019	0	-9999	-10000	0	0
cell proliferation	0.024	0.047	-9999	-0.15	32	32

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	-0.006	0.1	-10000	0	-0.25	65	65
epithelial cell differentiation	0.024	0.059	-10000	0	-0.18	34	34
CYFIP2	-0.019	0.098	-10000	0	-0.25	74	74
ENAH	0.014	0.068	-10000	0	-0.21	33	33
EGFR	-0.08	0.12	-10000	0	-0.18	267	267
EPHA2	0.008	0.036	-10000	0	-0.11	44	44
MYO6	0.011	0.065	-10000	0	-0.2	36	36
CTNNB1	0.017	0.023	-10000	0	-0.29	3	3
ABI1/Sra1/Nap1	0.009	0.071	-10000	0	-0.16	69	69
AQP5	0.017	0.089	-10000	0	-0.38	20	20
CTNND1	0.001	0.073	-10000	0	-0.29	31	31
mol:PI-4-5-P2	0.01	0.068	-10000	0	-0.21	39	39
regulation of calcium-dependent cell-cell adhesion	0.015	0.052	-10000	0	-0.16	34	34
EGF	0.014	0.025	-10000	0	-0.11	21	21
NCKAP1	0.019	0	-10000	0	-10000	0	0
AQP3	0.016	0.09	-10000	0	-0.38	20	20
cortical microtubule organization	0.024	0.059	-10000	0	-0.18	34	34
GO:0000145	0.005	0.063	-10000	0	-0.2	39	39
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.028	0.06	-10000	0	-0.18	34	34
MLLT4	0.019	0	-10000	0	-10000	0	0
ARF6/GDP	-0.018	0.054	-10000	0	-0.21	27	27
ARF6	0.018	0.015	-10000	0	-0.2	2	2
Ephrin A1/EPHA2/NCK1/GIT1	0.028	0.053	-10000	0	-0.14	36	36
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.017	0.13	-10000	0	-0.32	64	64
PVRL2	0.016	0.026	-10000	0	-0.19	7	7
ZYX	0.002	0.078	-10000	0	-0.23	44	44
ARF6/GTP	0.033	0.052	-10000	0	-0.14	31	31
CDH1	0.012	0.029	-10000	0	-0.11	28	28
EGFR/EGFR/EGF/EGF	-0.024	0.078	-10000	0	-0.15	101	101
RhoA/GDP	0.024	0.06	-10000	0	-0.17	38	38
actin cytoskeleton organization	0.012	0.065	-10000	0	-0.2	36	36
IGF-1R heterotetramer	-0.001	0.069	-10000	0	-0.21	46	46
GIT1	0.019	0.006	-10000	0	-0.11	1	1
IGF1R	-0.001	0.07	-10000	0	-0.21	46	46
IGF1	0.014	0.025	-10000	0	-0.11	21	21
DIAPH1	-0.034	0.21	-10000	0	-0.57	68	68
Wnt receptor signaling pathway	-0.024	0.059	0.18	34	-10000	0	34
RHOA	0.015	0.035	-10000	0	-0.29	7	7
RhoA/GTP	-0.019	0.057	-10000	0	-0.22	28	28
CTNNA1	0.011	0.048	-10000	0	-0.29	13	13
VCL	0.012	0.066	-10000	0	-0.2	36	36
EFNA1	-0.001	0.07	-10000	0	-0.21	47	47
LPP	0.004	0.075	-10000	0	-0.24	36	36
Ephrin A1/EPHA2	0.009	0.065	-10000	0	-0.15	59	59
SEC6/SEC8	-0.011	0.043	-10000	0	-0.22	16	16
MGAT3	0.015	0.053	-10000	0	-0.17	34	34
HGF/MET	0.016	0.055	-10000	0	-0.16	34	34
HGF	0.016	0.02	-10000	0	-0.11	13	13
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.006	0.11	-10000	0	-0.25	65	65
actin cable formation	-0.006	0.11	-10000	0	-0.27	60	60
KIAA1543	0.004	0.048	-10000	0	-0.16	34	34
KIFC3	0.015	0.053	-10000	0	-0.17	34	34
NCK1	0.014	0.036	-10000	0	-0.19	14	14
EXOC3	0.017	0.021	-10000	0	-0.2	4	4
ACTN1	0.003	0.073	-10000	0	-0.24	36	36
NCK1/GIT1	0.024	0.026	-10000	0	-0.19	6	6
mol:GDP	0.024	0.059	-10000	0	-0.18	34	34
EXOC4	0	0	-10000	0	-10000	0	0
STX4	0.013	0.064	-10000	0	-0.2	35	35
PIP5K1C	0.01	0.069	-10000	0	-0.21	39	39
LIMA1	-0.013	0.09	-10000	0	-0.24	65	65
ABI1	0.008	0.055	-10000	0	-0.24	22	22
ROCK1	0.017	0.066	-10000	0	-0.2	29	29
adherens junction assembly	0.007	0.088	-10000	0	-0.35	26	26
IGF-1R heterotetramer/IGF1	0.011	0.066	-10000	0	-0.16	50	50
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.026	0.018	-10000	0	-0.19	3	3
MET	0.007	0.037	-10000	0	-0.11	47	47
PLEKHA7	0.004	0.051	-10000	0	-0.17	34	34
mol:GTP	0.026	0.052	-10000	0	-0.14	36	36
establishment of epithelial cell apical/basal polarity	0.022	0.06	-10000	0	-0.25	18	18
cortical actin cytoskeleton stabilization	-0.006	0.1	-10000	0	-0.25	65	65
regulation of cell-cell adhesion	0.012	0.065	-10000	0	-0.2	36	36
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.006	0.11	-10000	0	-0.25	65	65

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	-0.035	0.11	-10000	0	-0.25	105	105
EPHB2	0.014	0.027	-10000	0	-0.11	24	24
EFNB1	0.02	0.011	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.028	0.052	-10000	0	-0.17	12	12
Ephrin B2/EPHB1-2	-0.008	0.072	-10000	0	-0.14	96	96
neuron projection morphogenesis	0.016	0.044	-10000	0	-0.16	12	12
Ephrin B1/EPHB1-2/Tiam1	0.024	0.048	-10000	0	-0.12	20	20
DNM1	0.017	0.017	-10000	0	-0.11	9	9
cell-cell signaling	0	0.002	-10000	0	-10000	0	0
MAP2K4	-0.041	0.17	-10000	0	-0.56	49	49
YES1	-0.06	0.24	-10000	0	-0.81	48	48
Ephrin B1/EPHB1-2/NCK2	0.028	0.044	-10000	0	-0.11	17	17
PI3K	-0.049	0.2	-10000	0	-0.63	52	52
mol:GDP	0.023	0.047	-10000	0	-0.11	20	20
ITGA2B	0.019	0	-10000	0	-10000	0	0
endothelial cell proliferation	-0.006	0.066	-10000	0	-0.16	83	83
FYN	-0.071	0.25	-10000	0	-0.84	48	48
MAP3K7	-0.046	0.18	-10000	0	-0.59	48	48
FGR	-0.059	0.23	-10000	0	-0.78	48	48
TIAM1	0.002	0.066	-10000	0	-0.23	36	36
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
RGS3	0.017	0.016	-10000	0	-0.11	8	8
cell adhesion	-0.038	0.19	-10000	0	-0.58	51	51
LYN	-0.073	0.23	-10000	0	-0.79	48	48
Ephrin B1/EPHB1-2/Src Family Kinases	-0.058	0.22	-10000	0	-0.74	48	48
Ephrin B1/EPHB1-2	-0.049	0.18	-10000	0	-0.63	48	48
SRC	-0.056	0.23	-10000	0	-0.77	48	48
ITGB3	0.019	0.008	-10000	0	-0.11	2	2
EPHB1	-0.005	0.057	-10000	0	-0.12	91	91
EPHB4	0.019	0.006	-10000	0	-0.11	1	1
RAC1	0.015	0.035	-10000	0	-0.29	7	7
Ephrin B2/EPHB4	-0.006	0.066	-10000	0	-0.16	83	83
alphaIIb/beta3 Integrin	0.028	0.006	-10000	0	-10000	0	0
BLK	-0.056	0.23	-10000	0	-0.77	48	48
HCK	-0.077	0.24	-10000	0	-0.8	48	48
regulation of stress fiber formation	-0.026	0.043	0.11	17	-10000	0	17
MAPK8	-0.035	0.16	-10000	0	-0.53	49	49
Ephrin B1/EPHB1-2/RGS3	0.032	0.038	-10000	0	-0.12	6	6
endothelial cell migration	-0.051	0.16	-10000	0	-0.55	48	48
NCK2	0.009	0.053	-10000	0	-0.28	17	17
PTPN13	-0.004	0.094	-10000	0	-0.36	31	31
regulation of focal adhesion formation	-0.026	0.043	0.11	17	-10000	0	17
chemotaxis	-0.03	0.037	0.11	6	-10000	0	6
PIK3CA	-0.011	0.085	-10000	0	-0.22	65	65
Rac1/GTP	0.022	0.048	-10000	0	-0.16	12	12
angiogenesis	-0.048	0.18	-10000	0	-0.62	48	48
LCK	-0.056	0.23	-10000	0	-0.78	48	48

×

Aurora B signaling

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
Condensin I complex	-0.026	0.13	-9999	-0.29	74	74
STMN1	0.007	0.044	-9999	-0.17	22	22
Aurora B/RasGAP/Survivin	-0.007	0.082	-9999	-0.16	107	107
Chromosomal passenger complex/Cul3 protein complex	-0.036	0.092	-9999	-0.21	76	76
BIRC5	-0.032	0.11	-9999	-0.22	111	111
DES	0.015	0.054	-9999	-1.1	1	1
Aurora C/Aurora B/INCENP	0.028	0.025	-9999	-0.11	5	5
Aurora B/TACC1	0.015	0.036	-9999	-0.17	15	15
Aurora B/PP2A	0.021	0.026	-9999	-0.16	3	3
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.002	0.06	-9999	-0.21	35	35
mitotic metaphase/anaphase transition	0	0.002	-9999	-10000	0	0
NDC80	-0.01	0.068	-9999	-0.18	65	65
Cul3 protein complex	-0.016	0.077	-9999	-0.16	116	116
KIF2C	-0.027	0.14	-9999	-0.38	53	53
PEBP1	0.011	0.048	-9999	-0.27	14	14
KIF20A	-0.029	0.1	-9999	-0.21	109	109
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	0.01	0.054	-9999	-0.2	29	29
SEPT1	0	0	-9999	-10000	0	0
SMC2	0	0.064	-9999	-0.17	53	53
SMC4	-0.009	0.083	-9999	-0.22	62	62
NSUN2/NPM1/Nucleolin	0	0.063	-9999	-0.39	4	4
PSMA3	0.012	0.043	-9999	-0.25	13	13
G2/M transition of mitotic cell cycle	0	0.003	-9999	-10000	0	0
H3F3B	0.008	0.039	-9999	-0.23	12	12
AURKB	0.01	0.035	-9999	-0.12	33	33
AURKC	0.015	0.022	-9999	-0.11	16	16
CDCA8	0.003	0.059	-9999	-0.17	44	44
cytokinesis	-0.036	0.17	-9999	-0.47	59	59
Aurora B/Septin1	-0.032	0.16	-9999	-0.44	59	59
AURKA	0.006	0.056	-9999	-0.2	32	32
INCENP	0.018	0.007	-9999	-0.12	1	1
KLHL13	0	0	-9999	-10000	0	0
BUB1	0.017	0.018	-9999	-0.11	10	10
hSgo1/Aurora B/Survivin	-0.007	0.061	-9999	-0.14	84	84
EVI5	0.018	0.008	-9999	-0.11	2	2
RhoA/GTP	-0.02	0.15	-9999	-0.34	72	72
SGOL1	0	0	-9999	-10000	0	0
CENPA	-0.016	0.12	-9999	-0.39	38	38
NCAPG	-0.018	0.089	-9999	-0.2	89	89
Aurora B/HC8 Proteasome	0.017	0.039	-9999	-0.18	14	14
NCAPD2	-0.008	0.079	-9999	-0.2	66	66
Aurora B/PP1-gamma	0.019	0.033	-9999	-0.2	7	7
RHOA	0.015	0.035	-9999	-0.29	7	7
NCAPH	0.011	0.034	-9999	-0.12	28	28
NPM1	0.005	0.053	-9999	-0.37	8	8
RASA1	0.003	0.069	-9999	-0.28	29	29
KLHL9	-0.052	0.13	-9999	-0.27	128	128
mitotic prometaphase	-0.001	0.003	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.017	0.039	-9999	-0.18	14	14
PPP1CC	0.016	0.033	-9999	-0.29	6	6
Centraspindlin	-0.027	0.16	-9999	-0.36	74	74
RhoA/GDP	0.011	0.024	-9999	-0.2	7	7
NSUN2	0.003	0.03	-9999	-0.47	1	1
MYLK	-0.033	0.091	-9999	-0.24	82	82
KIF23	-0.01	0.077	-9999	-0.18	78	78
VIM	-0.002	0.065	-9999	-0.21	44	44
RACGAP1	-0.013	0.091	-9999	-0.23	68	68
mitosis	0	0	-9999	-10000	0	0
NCL	0.002	0.065	-9999	-0.35	15	15
Chromosomal passenger complex	-0.021	0.12	-9999	-0.3	67	67
Chromosomal passenger complex/EVI5	0.011	0.081	-9999	-0.16	77	77
TACC1	0.01	0.049	-9999	-0.25	17	17
PPP2R5D	0.018	0.013	-9999	-0.11	5	5
CUL3	0.018	0.019	-9999	-0.29	2	2
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.001	0.005	0.02	3	-10000	0	3
BUB1B	-0.027	0.099	-10000	0	-0.28	60	60
PLK1	0.005	0.021	-10000	0	-0.07	21	21
PLK1S1	0.003	0.01	-10000	0	-0.035	8	8
KIF2A	-0.004	0.05	-10000	0	-0.14	52	52
regulation of mitotic centrosome separation	0.005	0.021	-10000	0	-0.07	21	21
GOLGA2	0.015	0.036	-10000	0	-0.27	8	8
Hec1/SPC24	-0.002	0.054	-10000	0	-0.14	61	61
WEE1	-0.03	0.15	-10000	0	-0.62	29	29
cytokinesis	-0.04	0.14	-10000	0	-0.38	64	64
PP2A-alpha B56	0.024	0.055	-10000	0	-0.29	4	4
AURKA	0.002	0.042	-10000	0	-0.23	15	15
PICH/PLK1	-0.028	0.12	-10000	0	-0.21	122	122
CENPE	-0.002	0.044	-10000	0	-0.13	40	40
RhoA/GTP	0.011	0.024	-10000	0	-0.2	7	7
positive regulation of microtubule depolymerization	-0.004	0.05	-10000	0	-0.14	52	52
PPP2CA	0.011	0.05	-10000	0	-0.28	15	15
FZR1	0.019	0	-10000	0	-10000	0	0
TPX2	-0.033	0.093	-10000	0	-0.24	90	90
PAK1	0.016	0.017	-10000	0	-0.11	9	9
SPC24	0	0	-10000	0	-10000	0	0
FBXW11	0.011	0.047	-10000	0	-0.26	14	14
CLSPN	0.01	0.012	-10000	0	-10000	0	0
GORASP1	0.006	0.061	-10000	0	-0.28	22	22
metaphase	-0.001	0.001	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.003	0.01	-10000	0	-0.035	8	8
G2 phase of mitotic cell cycle	-0.001	0.002	-10000	0	-0.01	15	15
STAG2	0.005	0.065	-10000	0	-0.29	24	24
GRASP65/GM130/RAB1/GTP	-0.018	0.15	-10000	0	-0.68	22	22
spindle elongation	0.005	0.021	-10000	0	-0.07	21	21
ODF2	0.016	0.018	-10000	0	-0.11	10	10
BUB1	0.014	0.027	-10000	0	-10000	0	0
TPT1	0.009	0.01	-10000	0	-10000	0	0
CDC25C	0.011	0.012	-10000	0	-10000	0	0
CDC25B	0.002	0.065	-10000	0	-0.27	26	26
SGOL1	0.001	0.005	-10000	0	-0.02	3	3
RHOA	0.015	0.035	-10000	0	-0.29	7	7
CCNB1/CDK1	-0.037	0.14	-10000	0	-0.29	108	108
CDC14B	0.003	0.036	-10000	0	-0.19	17	17
CDC20	-0.042	0.12	-10000	0	-0.24	127	127
PLK1/PBIP1	-0.018	0.058	-10000	0	-0.13	94	94
mitosis	0	0.006	0.032	15	-10000	0	15
FBXO5	-0.014	0.07	-10000	0	-0.21	49	49
CDC2	-0.032	0.1	-10000	0	-0.25	75	75
NDC80	-0.019	0.093	-10000	0	-0.21	89	89
metaphase plate congression	0.001	0.054	-10000	0	-0.3	16	16
ERCC6L	-0.037	0.14	-10000	0	-0.27	109	109
NLP/gamma Tubulin	0.001	0.027	-10000	0	-0.11	23	23
microtubule cytoskeleton organization	0.009	0.01	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	0	0.001	-10000	0	-10000	0	0
PPP1R12A	0.011	0.046	-10000	0	-0.24	15	15
interphase	0	0.001	-10000	0	-10000	0	0
PLK1/PRC1-2	-0.022	0.1	-10000	0	-0.19	118	118
GRASP65/GM130/RAB1/GTP/PLK1	0.023	0.051	-10000	0	-0.15	34	34
RAB1A	0.012	0.046	-10000	0	-0.29	12	12
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.004	0.025	-10000	0	-0.079	30	30
mitotic prometaphase	0	0.004	0.023	16	-10000	0	16
proteasomal ubiquitin-dependent protein catabolic process	0.009	0.073	-10000	0	-0.35	15	15
microtubule-based process	0.004	0.047	-10000	0	-0.13	43	43
Golgi organization	0.005	0.021	-10000	0	-0.07	21	21
Cohesin/SA2	0.008	0.037	-10000	0	-0.14	26	26
PPP1CB/MYPT1	0.02	0.041	-10000	0	-0.2	16	16
KIF20A	-0.028	0.1	-10000	0	-0.21	109	109
APC/C/CDC20	0.004	0.047	-10000	0	-0.13	41	41
PPP2R1A	0.003	0.068	-10000	0	-0.29	27	27
chromosome segregation	-0.018	0.057	-10000	0	-0.13	94	94
PRC1	-0.041	0.12	-10000	0	-0.24	122	122
ECT2	-0.011	0.058	-10000	0	-0.14	80	80
C13orf34	0.005	0.023	-10000	0	-0.069	29	29
NUDC	0.001	0.054	-10000	0	-0.3	16	16
regulation of attachment of spindle microtubules to kinetochore	-0.027	0.098	-10000	0	-0.28	60	60
spindle assembly	0.003	0.024	-10000	0	-0.076	29	29
spindle stabilization	0.003	0.01	-10000	0	-0.035	8	8
APC/C/HCDH1	0.016	0.031	-10000	0	-0.16	16	16
MKLP2/PLK1	0.004	0.047	-10000	0	-0.13	43	43
CCNB1	-0.04	0.12	-10000	0	-0.24	119	119
PPP1CB	0.015	0.034	-10000	0	-0.27	7	7
BTRC	0.019	0	-10000	0	-10000	0	0
ROCK2	0.013	0.027	-10000	0	-0.16	7	7
TUBG1	-0.001	0.052	-10000	0	-0.25	22	22
G2/M transition of mitotic cell cycle	-0.064	0.13	-10000	0	-0.29	107	107
MLF1IP	-0.033	0.078	-10000	0	-0.2	84	84
INCENP	0.019	0.006	-10000	0	-0.11	1	1

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0.016	0.029	-10000	0	-0.2	8	8
MKNK1	0.003	0.068	-10000	0	-0.27	30	30
mol:PIP3	-0.025	0.083	0.19	4	-0.18	93	97
FRAP1	-0.003	0.09	-10000	0	-0.55	12	12
AKT1	-0.022	0.093	0.19	4	-0.19	96	100
INSR	0.019	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.026	0	-10000	0	-10000	0	0
mol:GTP	-0.007	0.098	0.17	4	-0.24	55	59
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.022	0.055	-10000	0	-0.18	41	41
TSC2	0.009	0.05	-10000	0	-0.22	21	21
RHEB/GDP	-0.011	0.085	-10000	0	-0.21	54	54
TSC1	0.008	0.055	-10000	0	-0.25	21	21
Insulin Receptor/IRS1	0.004	0.063	-10000	0	-0.27	25	25
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.002	0.068	-10000	0	-0.2	39	39
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.011	0.047	-10000	0	-0.29	12	12
RPS6KB1	-0.001	0.066	0.16	3	-0.22	24	27
MAP3K5	-0.02	0.087	-10000	0	-0.29	49	49
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
apoptosis	-0.019	0.087	-10000	0	-0.29	49	49
mol:LY294002	0	0	0.001	24	-0.001	20	44
EIF4B	0.002	0.066	0.16	3	-0.22	22	25
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.011	0.068	0.15	3	-0.21	27	30
eIF4E/eIF4G1/eIF4A1	-0.022	0.065	-10000	0	-0.29	22	22
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	-0.013	0.091	-10000	0	-0.18	99	99
mTOR/RHEB/GTP/Raptor/GBL	0.009	0.057	0.15	4	-0.19	21	25
FKBP1A	0.007	0.052	-10000	0	-0.18	31	31
RHEB/GTP	-0.002	0.088	-10000	0	-0.22	48	48
mol:Amino Acids	0	0	0.001	24	-0.001	20	44
FKBP12/Rapamycin	0.006	0.035	-10000	0	-0.12	31	31
PDPK1	-0.019	0.079	0.19	4	-0.16	93	97
EIF4E	0.002	0.07	-10000	0	-0.27	31	31
ASK1/PP5C	-0.038	0.19	-10000	0	-0.57	58	58
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.002	0.097	-10000	0	-0.37	31	31
TSC1/TSC2	-0.007	0.11	0.19	4	-0.26	55	59
tumor necrosis factor receptor activity	0	0	0.001	20	-0.001	24	44
RPS6	0.015	0.035	-10000	0	-0.29	7	7
PPP5C	0.017	0.015	-10000	0	-0.11	7	7
EIF4G1	0	0.072	-10000	0	-0.27	34	34
IRS1	-0.009	0.065	-10000	0	-0.3	25	25
INS	0.019	0	-10000	0	-10000	0	0
PTEN	0.013	0.037	-10000	0	-0.18	16	16
PDK2	-0.019	0.079	0.19	4	-0.16	93	97
EIF4EBP1	-0.042	0.26	-10000	0	-1.1	27	27
PIK3CA	-0.011	0.085	-10000	0	-0.22	65	65
PPP2R5D	0.002	0.08	-10000	0	-0.48	12	12
peptide biosynthetic process	0.023	0.003	-10000	0	-10000	0	0
RHEB	0.019	0	-10000	0	-10000	0	0
EIF4A1	0.015	0.033	-10000	0	-0.26	7	7
mol:Rapamycin	0	0.001	0.003	5	-0.002	36	41
EEF2	0.023	0.003	-10000	0	-10000	0	0
eIF4E/4E-BP1	-0.032	0.25	-10000	0	-1.1	27	27

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.011	0.097	-9999	-0.45	6	6
UGCG	-0.029	0.19	-9999	-0.81	28	28
AKT1/mTOR/p70S6K/Hsp90/TERT	0.01	0.14	-9999	-0.35	44	44
mol:GTP	0	0	-9999	-10000	0	0
mol:glucosylceramide	-0.028	0.19	-9999	-0.79	28	28
mol:DAG	-0.013	0.12	-9999	-0.92	9	9
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.01	0.19	-9999	-0.41	79	79
FRAP1	-0.016	0.21	-9999	-0.45	80	80
FOXO3	-0.028	0.22	-9999	-0.47	86	86
AKT1	-0.031	0.23	-9999	-0.49	83	83
GAB2	-0.005	0.082	-9999	-0.27	44	44
SMPD1	0.013	0.034	-9999	-10000	0	0
SGMS1	-0.002	0.097	-9999	-0.67	9	9
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
mol:GDP	-0.018	0.074	-9999	-0.17	87	87
CALM1	0.007	0.056	-9999	-0.21	28	28
cell proliferation	-0.035	0.2	-9999	-0.38	86	86
EIF3A	0.011	0.047	-9999	-0.29	12	12
PI3K	-0.013	0.093	-9999	-0.21	87	87
RPS6KB1	0.02	0.024	-9999	-10000	0	0
mol:sphingomyelin	-0.013	0.12	-9999	-0.92	9	9
natural killer cell activation	0	0.003	-9999	-0.01	48	48
JAK3	0.02	0.004	-9999	-10000	0	0
PIK3R1	-0.013	0.095	-9999	-0.27	62	62
JAK1	0.002	0.071	-9999	-0.26	34	34
NFKB1	0.014	0.038	-9999	-0.22	12	12
MYC	-0.068	0.31	-9999	-0.82	70	70
MYB	0.028	0.029	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.012	0.17	-9999	-0.4	60	60
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.035	0.039	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.01	0.17	-9999	-0.39	60	60
Rac1/GDP	-0.007	0.076	-9999	-0.16	88	88
T cell proliferation	-0.009	0.16	-9999	-0.37	60	60
SHC1	0.004	0.052	-9999	-0.14	48	48
RAC1	0.015	0.035	-9999	-0.29	7	7
positive regulation of cyclin-dependent protein kinase activity	0.004	0.004	-9999	-10000	0	0
PRKCZ	-0.011	0.16	-9999	-0.38	60	60
NF kappa B1 p50/RelA	0.001	0.19	-9999	-0.4	77	77
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.006	0.1	-9999	-0.34	27	27
HSP90AA1	0.018	0.019	-9999	-0.29	2	2
RELA	0.018	0.02	-9999	-0.23	3	3
IL2RA	0.012	0.029	-9999	-0.11	28	28
IL2RB	0.016	0.024	-9999	-0.11	19	19
TERT	0.019	0.008	-9999	-0.11	2	2
E2F1	0.026	0.021	-9999	-10000	0	0
SOS1	0	0.003	-9999	-0.009	48	48
RPS6	0.015	0.035	-9999	-0.29	7	7
mol:cAMP	-0.002	0.002	-9999	-10000	0	0
PTPN11	0.015	0.034	-9999	-0.26	7	7
IL2RG	0.014	0.027	-9999	-0.11	24	24
actin cytoskeleton organization	-0.009	0.16	-9999	-0.37	60	60
GRB2	0.014	0.039	-9999	-0.26	10	10
IL2	0.02	0.007	-9999	-0.12	1	1
PIK3CA	-0.009	0.085	-9999	-0.22	65	65
Rac1/GTP	0.005	0.078	-9999	-0.15	88	88
LCK	0.018	0.016	-9999	-0.11	8	8
BCL2	0.002	0.16	-9999	-0.44	36	36

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.018	0.01	-10000	0	-0.11	3	3
RAS family/GTP/Tiam1	-0.006	0.096	-10000	0	-0.32	30	30
NT3 (dimer)/TRKC	0.021	0.033	-10000	0	-0.2	8	8
NT3 (dimer)/TRKB	-0.011	0.074	-10000	0	-0.15	96	96
SHC/Grb2/SOS1/GAB1/PI3K	-0.022	0.11	-10000	0	-0.23	92	92
RAPGEF1	0.019	0	-10000	0	-10000	0	0
BDNF	0.004	0.042	-10000	0	-0.11	61	61
PIK3CA	-0.011	0.085	-10000	0	-0.22	65	65
DYNLT1	0.012	0.045	-10000	0	-0.28	12	12
NTRK1	0.018	0.011	-10000	0	-0.11	4	4
NTRK2	-0.044	0.12	-10000	0	-0.23	133	133
NTRK3	0.009	0.045	-10000	0	-0.16	29	29
NT-4/5 (dimer)/TRKB	-0.021	0.07	-10000	0	-0.16	96	96
neuron apoptosis	0.033	0.13	0.33	61	-10000	0	61
SHC 2-3/Grb2	-0.036	0.14	-10000	0	-0.36	61	61
SHC1	0.004	0.052	-10000	0	-0.14	48	48
SHC2	-0.04	0.13	-10000	0	-0.4	48	48
SHC3	-0.041	0.13	-10000	0	-0.4	46	46
STAT3 (dimer)	-0.024	0.12	-10000	0	-0.32	63	63
NT3 (dimer)/TRKA	0.027	0.03	-10000	0	-0.1	2	2
RIN/GDP	0.001	0.075	-10000	0	-0.2	43	43
GIPC1	0.019	0	-10000	0	-10000	0	0
KRAS	0.011	0.048	-10000	0	-0.28	14	14
DNAJA3	-0.004	0.044	0.18	3	-0.17	8	11
RIN/GTP	-0.019	0.056	-10000	0	-0.092	163	163
CCND1	-0.039	0.15	-10000	0	-0.4	63	63
MAGED1	0.004	0.066	-10000	0	-0.28	26	26
PTPN11	0.015	0.033	-10000	0	-0.26	7	7
RICS	0.001	0.066	-10000	0	-0.21	41	41
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.014	0.039	-10000	0	-0.17	16	16
GRB2	0.014	0.039	-10000	0	-0.26	10	10
NGF (dimer)/TRKA/MATK	0.025	0.009	-10000	0	-10000	0	0
TRKA/NEDD4-2	0.022	0.024	-10000	0	-0.19	1	1
ELMO1	-0.046	0.11	-10000	0	-0.21	153	153
RhoG/GTP/ELMO1/DOCK1	-0.017	0.073	-10000	0	-0.16	90	90
NGF	0	0	-10000	0	-10000	0	0
HRAS	0.009	0.055	-10000	0	-0.28	18	18
DOCK1	0.011	0.046	-10000	0	-0.22	18	18
GAB2	-0.005	0.082	-10000	0	-0.27	44	44
RIT2	-0.031	0.084	-10000	0	-0.14	163	163
RIT1	-0.008	0.082	-10000	0	-0.23	57	57
FRS2	0.018	0.013	-10000	0	-0.11	5	5
DNM1	0.017	0.017	-10000	0	-0.11	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.009	0.053	-10000	0	-0.28	17	17
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.022	0.069	0.17	3	-0.2	37	40
mol:GDP	0.005	0.1	-10000	0	-0.29	40	40
NGF (dimer)	0	0	-10000	0	-10000	0	0
RhoG/GDP	-0.03	0.076	-10000	0	-0.14	153	153
RIT1/GDP	0.007	0.081	-10000	0	-0.2	49	49
TIAM1	0.002	0.066	-10000	0	-0.23	36	36
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
BDNF (dimer)/TRKB	-0.016	0.083	-10000	0	-0.17	108	108
KIDINS220/CRKL/C3G	0.028	0.007	-10000	0	-10000	0	0
SHC/RasGAP	0.007	0.062	-10000	0	-0.2	35	35
FRS2 family/SHP2	0.036	0.022	-10000	0	-0.15	6	6
SHC/GRB2/SOS1/GAB1	0.016	0.047	-10000	0	-0.14	29	29
RIT1/GTP	-0.004	0.056	-10000	0	-0.15	57	57
NT3 (dimer)	0.018	0.01	-10000	0	-0.11	3	3
RAP1/GDP	-0.017	0.049	-10000	0	-0.16	44	44
KIDINS220/CRKL	0.018	0.01	-10000	0	-0.11	3	3
BDNF (dimer)	0.004	0.042	-10000	0	-0.11	61	61
ubiquitin-dependent protein catabolic process	0.02	0.02	-10000	0	-0.16	1	1
Schwann cell development	-0.014	0.021	-10000	0	-0.087	11	11
EHD4	0.006	0.058	-10000	0	-0.29	18	18
FRS2 family/GRB2/SOS1	0.033	0.023	-10000	0	-0.14	8	8
FRS2 family/SHP2/CRK family/C3G/GAB2	0.018	0.071	-10000	0	-0.34	12	12
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0.018	0.019	-10000	0	-0.29	2	2
CDC42/GTP	-0.017	0.089	-10000	0	-0.21	65	65
ABL1	-0.012	0.093	-10000	0	-0.28	55	55
SH2B family/GRB2/SOS1	0.011	0.026	-10000	0	-0.17	10	10
Rap1/GTP	0.01	0.055	-10000	0	-0.2	11	11
STAT3	-0.024	0.12	-10000	0	-0.32	63	63
axon guidance	-0.023	0.083	-10000	0	-0.2	65	65
MAPK3	0.022	0.008	-10000	0	-10000	0	0
MAPK1	0.021	0.014	-10000	0	-0.19	1	1
CDC42/GDP	0.013	0.072	-10000	0	-0.2	36	36
NTF3	0.018	0.01	-10000	0	-0.11	3	3
NTF4	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/FAIM	0.021	0.027	-10000	0	-0.16	10	10
PI3K	-0.015	0.092	-10000	0	-0.21	87	87
FRS3	0.019	0.006	-10000	0	-0.11	1	1
FAIM	0.011	0.045	-10000	0	-0.21	18	18
GAB1	0.003	0.056	-10000	0	-0.15	50	50
RASGRF1	-0.003	0.043	0.16	4	-0.15	9	13
SOS1	0	0	-10000	0	-10000	0	0
MCF2L	0.012	0.042	-10000	0	-0.19	15	15
RGS19	0.013	0.041	-10000	0	-0.26	11	11
CDC42	0.017	0.016	-10000	0	-0.11	8	8
RAS family/GTP	0.008	0.099	-10000	0	-0.39	23	23
Rac1/GDP	0.012	0.075	-10000	0	-0.21	36	36
NGF (dimer)/TRKA/GRIT	0.015	0.039	-10000	0	-0.16	22	22
neuron projection morphogenesis	-0.066	0.26	-10000	0	-0.84	45	45
NGF (dimer)/TRKA/NEDD4-2	0.021	0.02	-10000	0	-0.16	1	1
MAP2K1	0.009	0.045	-10000	0	-0.15	29	29
NGFR	0.002	0.044	-10000	0	-0.11	70	70
NGF (dimer)/TRKA/GIPC/GAIP	0.023	0.047	-10000	0	-0.22	16	16
RAS family/GTP/PI3K	-0.032	0.12	-10000	0	-0.22	126	126
FRS2 family/SHP2/GRB2/SOS1	0.04	0.033	-10000	0	-0.18	10	10
NRAS	-0.01	0.086	-10000	0	-0.29	42	42
GRB2/SOS1	0.011	0.026	-10000	0	-0.17	10	10
PRKCI	0.015	0.028	-10000	0	-0.14	15	15
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.015	0.035	-10000	0	-0.29	7	7
PRKCZ	0	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.008	0.079	-10000	0	-0.52	10	10
RASA1	0.003	0.069	-10000	0	-0.28	29	29
TRKA/c-Abl	0.006	0.066	-10000	0	-0.19	52	52
SQSTM1	0.004	0.062	-10000	0	-0.29	20	20
BDNF (dimer)/TRKB/GIPC	0	0.077	-10000	0	-0.15	95	95
NGF (dimer)/TRKA/p62/Atypical PKCs	0.024	0.035	-10000	0	-0.13	22	22
MATK	0.018	0.01	-10000	0	-0.11	3	3
NEDD4L	0.011	0.033	-10000	0	-0.12	31	31
RAS family/GDP	-0.025	0.056	-10000	0	-0.17	55	55
NGF (dimer)/TRKA	-0.007	0.045	0.18	4	-0.16	9	13
Rac1/GTP	-0.035	0.068	-10000	0	-0.22	49	49
FRS2 family/SHP2/CRK family	0.048	0.038	-10000	0	-0.13	20	20

×

FoxO family signaling

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
G6PC	0.013	0.082	-9999	-0.46	2	2
PLK1	-0.042	0.22	-9999	-0.67	24	24
CDKN1B	-0.037	0.19	-9999	-0.38	84	84
FOXO3	-0.051	0.24	-9999	-0.46	105	105
KAT2B	-0.003	0.02	-9999	-0.043	90	90
FOXO1/SIRT1	0.005	0.09	-9999	-0.29	34	34
CAT	-0.054	0.27	-9999	-0.98	25	25
CTNNB1	0.017	0.023	-9999	-0.29	3	3
AKT1	0.002	0.069	-9999	-0.26	28	28
FOXO1	0.006	0.09	-9999	-0.33	24	24
MAPK10	-0.002	0.069	-9999	-0.18	60	60
mol:GTP	-0.001	0.004	-9999	-10000	0	0
FOXO4	-0.029	0.21	-9999	-0.49	62	62
response to oxidative stress	-0.001	0.022	-9999	-0.044	69	69
FOXO3A/SIRT1	-0.066	0.23	-9999	-0.46	109	109
XPO1	0.017	0.023	-9999	-0.29	3	3
EP300	0.013	0.046	-9999	-0.24	15	15
BCL2L11	0.018	0.031	-9999	-10000	0	0
FOXO1/SKP2	0.013	0.085	-9999	-0.31	24	24
mol:GDP	-0.001	0.022	-9999	-0.044	69	69
RAN	0.015	0.031	-9999	-0.24	7	7
GADD45A	-0.1	0.34	-9999	-0.9	74	74
YWHAQ	0.018	0.019	-9999	-0.29	2	2
FOXO1/14-3-3 family	0.018	0.16	-9999	-0.55	24	24
MST1	0.011	0.03	-9999	-0.12	13	13
CSNK1D	0.01	0.052	-9999	-0.27	17	17
CSNK1E	0.003	0.064	-9999	-0.23	34	34
FOXO4/14-3-3 family	0	0.16	-9999	-0.44	38	38
YWHAB	0.015	0.035	-9999	-0.29	7	7
MAPK8	0.01	0.047	-9999	-0.15	29	29
MAPK9	0.009	0.05	-9999	-0.16	31	31
YWHAG	0	0	-9999	-10000	0	0
YWHAE	0.011	0.045	-9999	-0.21	19	19
YWHAZ	0.014	0.037	-9999	-0.29	7	7
SIRT1	0.004	0.048	-9999	-0.17	32	32
SOD2	-0.13	0.36	-9999	-0.81	104	104
RBL2	-0.061	0.3	-9999	-1	32	32
RAL/GDP	0.012	0.051	-9999	-0.17	28	28
CHUK	0.012	0.033	-9999	-0.16	9	9
Ran/GTP	0.011	0.023	-9999	-0.17	7	7
CSNK1G2	0.018	0.013	-9999	-0.29	1	1
RAL/GTP	0.013	0.051	-9999	-0.16	29	29
CSNK1G1	0.019	0	-9999	-10000	0	0
FASLG	0.018	0.031	-9999	-10000	0	0
SKP2	0.017	0.018	-9999	-0.11	10	10
USP7	0.014	0.039	-9999	-0.27	9	9
IKBKB	0.014	0.023	-9999	-10000	0	0
CCNB1	-0.16	0.45	-9999	-1.1	97	97
FOXO1-3a-4/beta catenin	-0.033	0.21	-9999	-0.4	87	87
proteasomal ubiquitin-dependent protein catabolic process	0.013	0.085	-9999	-0.31	24	24
CSNK1A1	0.014	0.038	-9999	-0.29	8	8
SGK1	-0.003	0.02	-9999	-0.043	90	90
CSNK1G3	0.017	0.025	-9999	-0.29	3	3
Ran/GTP/Exportin 1	0.022	0.029	-9999	-0.21	6	6
ZFAND5	-0.013	0.18	-9999	-0.55	32	32
SFN	0.002	0.044	-9999	-0.11	70	70
CDK2	0.014	0.034	-9999	-0.17	6	6
FOXO3A/14-3-3	-0.004	0.17	-9999	-0.48	36	36
CREBBP	0.022	0.002	-9999	-10000	0	0
FBXO32	-0.046	0.22	-9999	-0.42	105	105
BCL6	-0.085	0.34	-9999	-1.1	42	42
RALB	0.013	0.037	-9999	-0.19	15	15
RALA	0.005	0.063	-9999	-0.26	26	26
YWHAH	-0.006	0.082	-9999	-0.25	49	49

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.002	0.048	-10000	0	-0.25	15	15
HSPA8	0.01	0.056	-10000	0	-0.29	18	18
SMAD3/SMAD4/ER alpha	0.045	0.078	0.2	33	-0.16	21	54
AKT1	0.006	0.064	-10000	0	-0.25	28	28
GSC	0.013	0.024	-10000	0	-10000	0	0
NKX2-5	0.014	0.025	-10000	0	-0.11	18	18
muscle cell differentiation	-0.009	0.11	0.31	44	-10000	0	44
SMAD2-3/SMAD4/SP1	0.018	0.12	-10000	0	-0.26	55	55
SMAD4	0.007	0.069	-10000	0	-0.21	31	31
CBFB	0.017	0.018	-10000	0	-0.15	5	5
SAP18	0.011	0.052	-10000	0	-0.29	15	15
Cbp/p300/MSG1	-0.023	0.081	-10000	0	-0.17	107	107
SMAD3/SMAD4/VDR	0.021	0.09	-10000	0	-0.22	41	41
MYC	-0.026	0.097	-10000	0	-0.22	95	95
CDKN2B	0.029	0.048	-10000	0	-10000	0	0
AP1	-0.007	0.13	-10000	0	-0.32	61	61
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.007	0.15	-10000	0	-0.46	32	32
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.025	0.18	-10000	0	-0.45	56	56
SP3	0.012	0.047	-10000	0	-0.29	12	12
CREB1	0.015	0.033	-10000	0	-0.26	7	7
FOXH1	0.019	0.01	-10000	0	-10000	0	0
SMAD3/SMAD4/GR	0.036	0.083	-10000	0	-0.2	32	32
GATA3	0.023	0.018	-10000	0	-0.1	2	2
SKI/SIN3/HDAC complex/NCoR1	0.012	0.1	-10000	0	-0.36	23	23
MEF2C/TIF2	0.028	0.076	-10000	0	-0.27	24	24
endothelial cell migration	0.28	0.51	1.3	112	-10000	0	112
MAX	0.029	0.018	-10000	0	-10000	0	0
RBBP7	0.016	0.034	-10000	0	-0.24	8	8
RBBP4	-0.005	0.079	-10000	0	-0.24	50	50
RUNX2	0.019	0	-10000	0	-10000	0	0
RUNX3	0.014	0.024	-10000	0	-0.11	19	19
RUNX1	0.019	0	-10000	0	-10000	0	0
CTBP1	0.007	0.059	-10000	0	-0.29	20	20
NR3C1	0.024	0.041	-10000	0	-0.29	7	7
VDR	0.019	0.008	-10000	0	-0.11	2	2
CDKN1A	-0.12	0.39	-10000	0	-1.2	62	62
KAT2B	-0.004	0.007	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	0.025	0.072	-10000	0	-0.21	31	31
DCP1A	0.012	0.046	-10000	0	-0.29	12	12
SKI	0.02	0.001	-10000	0	-10000	0	0
SERPINE1	-0.28	0.52	-10000	0	-1.3	112	112
SMAD3/SMAD4/ATF2	0.022	0.071	-10000	0	-0.18	27	27
SMAD3/SMAD4/ATF3	-0.009	0.11	-10000	0	-0.2	90	90
SAP30	0.017	0.027	-10000	0	-0.29	4	4
Cbp/p300/PIAS3	0.014	0.046	-10000	0	-0.17	17	17
JUN	-0.014	0.13	-10000	0	-0.32	61	61
SMAD3/SMAD4/IRF7	0.024	0.077	-10000	0	-0.18	31	31
TFE3	-0.006	0.065	-10000	0	-0.19	40	40
COL1A2	-0.13	0.26	-10000	0	-0.72	81	81
mesenchymal cell differentiation	-0.023	0.07	0.18	27	-10000	0	27
DLX1	0	0	-10000	0	-10000	0	0
TCF3	0.019	0	-10000	0	-10000	0	0
FOS	-0.018	0.093	-10000	0	-0.19	93	93
SMAD3/SMAD4/Max	0.041	0.072	0.17	19	-0.17	23	42
Cbp/p300/SNIP1	0.024	0.033	-10000	0	-0.16	11	11
ZBTB17	0.017	0.006	-10000	0	-0.11	1	1
LAMC1	-0.009	0.12	-10000	0	-0.34	50	50
TGIF2/HDAC complex/SMAD3/SMAD4	0.021	0.072	-10000	0	-0.16	43	43
IRF7	0.014	0.043	-10000	0	-0.17	24	24
ESR1	0.029	0.025	-10000	0	-10000	0	0
HNF4A	0.019	0	-10000	0	-10000	0	0
MEF2C	0.018	0.078	-10000	0	-0.29	24	24
SMAD2-3/SMAD4	0.022	0.087	-10000	0	-0.24	30	30
Cbp/p300/Src-1	0.007	0.064	-10000	0	-0.18	48	48
IGHV3OR16-13	-0.005	0.063	-10000	0	-0.59	6	6
TGIF2/HDAC complex	0.014	0.024	-10000	0	-0.11	19	19
CREBBP	0.012	0.013	-10000	0	-10000	0	0
SKIL	0.019	0.006	-10000	0	-0.11	1	1
HDAC1	0.014	0.04	-10000	0	-0.22	13	13
HDAC2	0.005	0.061	-10000	0	-0.21	33	33
SNIP1	0.02	0.01	-10000	0	-0.11	2	2
GCN5L2	0.008	0.03	-10000	0	-0.18	9	9
SMAD3/SMAD4/TFE3	0.009	0.11	-10000	0	-0.24	63	63
MSG1/HSC70	-0.027	0.093	-10000	0	-0.2	111	111
SMAD2	0.013	0.05	-10000	0	-0.29	13	13
SMAD3	0.015	0.041	-10000	0	-0.11	27	27
SMAD3/E2F4-5/DP1/p107/SMAD4	0.013	0.073	-10000	0	-0.2	38	38
SMAD2/SMAD2/SMAD4	-0.011	0.065	0.13	1	-0.22	37	38
NCOR1	0.01	0.054	-10000	0	-0.27	18	18
NCOA2	0.018	0.01	-10000	0	-10000	0	0
NCOA1	-0.006	0.083	-10000	0	-0.28	43	43
MYOD/E2A	0.028	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.03	0.12	-10000	0	-0.25	47	47
IFNB1	0.023	0.062	-10000	0	-0.2	15	15
SMAD3/SMAD4/MEF2C	0.034	0.094	-10000	0	-0.28	27	27
CITED1	-0.054	0.12	-10000	0	-0.22	162	162
SMAD2-3/SMAD4/ARC105	0.036	0.082	-10000	0	-0.24	23	23
RBL1	0	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.01	0.17	-10000	0	-0.45	47	47
RUNX1-3/PEBPB2	0.035	0.019	-10000	0	-0.15	1	1
SMAD7	-0.041	0.2	-10000	0	-0.52	59	59
MYC/MIZ-1	-0.007	0.068	-10000	0	-0.2	53	53
SMAD3/SMAD4	-0.1	0.21	-10000	0	-0.46	118	118
IL10	0.03	0.059	-10000	0	-0.2	11	11
PIASy/HDAC complex	0.025	0.012	-10000	0	-0.11	1	1
PIAS3	0.011	0.034	-10000	0	-0.19	12	12
CDK2	0.005	0.037	-10000	0	-0.13	29	29
IL5	0.03	0.059	-10000	0	-0.21	11	11
CDK4	-0.013	0.067	-10000	0	-0.15	80	80
PIAS4	0.025	0.012	-10000	0	-0.11	1	1
ATF3	-0.036	0.11	-10000	0	-0.22	121	121
SMAD3/SMAD4/SP1	0.001	0.12	-10000	0	-0.23	73	73
FOXG1	-0.029	0.11	-10000	0	-0.26	89	89
FOXO3	0.012	0.049	-10000	0	-0.22	19	19
FOXO1	0.003	0.059	-10000	0	-0.2	35	35
FOXO4	0.013	0.044	-10000	0	-0.19	22	22
heart looping	0.018	0.078	-10000	0	-0.29	24	24
CEBPB	-0.003	0.076	-10000	0	-0.22	51	51
SMAD3/SMAD4/DLX1	0.012	0.067	-10000	0	-0.15	49	49
MYOD1	0.019	0	-10000	0	-10000	0	0
SMAD3/SMAD4/HNF4	0.023	0.07	-10000	0	-0.18	27	27
SMAD3/SMAD4/GATA3	0.036	0.075	-10000	0	-0.19	20	20
SnoN/SIN3/HDAC complex/NCoR1	0.019	0.006	-10000	0	-0.11	1	1
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.042	0.066	-10000	0	-0.18	13	13
SMAD3/SMAD4/SP1-3	0.014	0.12	-10000	0	-0.25	57	57
MED15	0.018	0.013	-10000	0	-0.11	5	5
SP1	-0.011	0.057	-10000	0	-0.11	100	100
SIN3B	0.017	0.025	-10000	0	-0.29	3	3
SIN3A	0.001	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.038	0.076	-10000	0	-0.22	29	29
ITGB5	-0.004	0.11	-10000	0	-0.27	50	50
TGIF/SIN3/HDAC complex/CtBP	-0.004	0.13	-10000	0	-0.43	29	29
SMAD3/SMAD4/AR	0.02	0.071	-10000	0	-0.18	29	29
AR	0.014	0.026	-10000	0	-0.11	22	22
negative regulation of cell growth	-0.018	0.14	-10000	0	-0.32	69	69
SMAD3/SMAD4/MYOD	0.023	0.07	-10000	0	-0.18	27	27
E2F5	0.019	0	-10000	0	-10000	0	0
E2F4	0.019	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.031	0.08	-10000	0	-0.22	32	32
SMAD2-3/SMAD4/FOXO1-3a-4	-0.01	0.16	-10000	0	-0.47	40	40
TFDP1	0.005	0.058	-10000	0	-0.2	33	33
SMAD3/SMAD4/AP1	0.002	0.14	-10000	0	-0.32	61	61
SMAD3/SMAD4/RUNX2	0.023	0.07	-10000	0	-0.18	27	27
TGIF2	0.014	0.024	-10000	0	-0.11	19	19
TGIF1	-0.005	0.076	-10000	0	-0.21	54	54
ATF2	0.017	0.017	-10000	0	-0.11	9	9

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.005	0.079	-10000	0	-0.25	38	38
BIRC5	-0.03	0.1	-10000	0	-0.22	111	111
NFKBIA	0.007	0.06	-10000	0	-0.18	43	43
CPEB1	-0.004	0.076	-10000	0	-0.22	50	50
AKT1	0.009	0.066	-10000	0	-0.24	29	29
NDEL1	0.013	0.043	-10000	0	-0.28	11	11
Aurora A/BRCA1	0.015	0.049	-10000	0	-0.18	25	25
NDEL1/TACC3	0.013	0.071	-10000	0	-0.18	47	47
GADD45A	-0.022	0.1	-10000	0	-0.26	78	78
GSK3B	0.007	0.064	-10000	0	-0.26	26	26
PAK1/Aurora A	0.016	0.056	-10000	0	-0.2	25	25
MDM2	0.011	0.032	-10000	0	-0.11	34	34
JUB	0	0	-10000	0	-10000	0	0
TPX2	-0.019	0.079	-10000	0	-0.19	89	89
TP53	0.004	0.081	-10000	0	-0.28	33	33
DLG7	-0.011	0.069	-10000	0	-0.17	66	66
AURKAIP1	0.018	0.015	-10000	0	-0.2	2	2
ARHGEF7	0	0.071	-10000	0	-0.25	37	37
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.014	0.075	-10000	0	-0.2	47	47
G2/M transition of mitotic cell cycle	0.015	0.049	-10000	0	-0.18	25	25
AURKA	0.012	0.063	0.14	16	-0.24	25	41
AURKB	0.006	0.037	-10000	0	-0.16	17	17
CDC25B	0.002	0.095	-10000	0	-0.32	36	36
G2/M transition checkpoint	0.003	0.047	-10000	0	-0.18	25	25
mRNA polyadenylation	0.004	0.064	-10000	0	-0.16	57	57
Aurora A/CPEB	0.005	0.064	-10000	0	-0.16	57	57
Aurora A/TACC1/TRAP/chTOG	0.021	0.087	-10000	0	-0.25	35	35
BRCA1	0.017	0.015	-10000	0	-0.11	7	7
centrosome duplication	0.016	0.056	-10000	0	-0.2	25	25
regulation of centrosome cycle	0.012	0.07	-10000	0	-0.18	47	47
spindle assembly	0.02	0.085	-10000	0	-0.24	35	35
TDRD7	0.004	0.065	-10000	0	-0.27	27	27
Aurora A/RasGAP/Survivin	0.004	0.086	-10000	0	-0.23	42	42
CENPA	-0.006	0.092	-10000	0	-0.35	31	31
Aurora A/PP2A	0.017	0.055	-10000	0	-0.2	25	25
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	0	0.077	-10000	0	-0.24	37	37
negative regulation of DNA binding	0	0.084	-10000	0	-0.28	33	33
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.015	0.05	-10000	0	-0.19	28	28
RASA1	0.003	0.069	-10000	0	-0.28	29	29
Ajuba/Aurora A	0.004	0.047	-10000	0	-0.18	25	25
mitotic prometaphase	-0.001	0.005	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.012	0.063	0.14	16	-0.24	25	41
TACC1	0.01	0.049	-10000	0	-0.25	17	17
TACC3	-0.004	0.074	-10000	0	-0.21	54	54
Aurora A/Antizyme1	0.027	0.053	-10000	0	-0.18	27	27
Aurora A/RasGAP	0.012	0.073	-10000	0	-0.29	25	25
OAZ1	0.017	0.023	-10000	0	-0.29	3	3
RAN	0.016	0.031	-10000	0	-0.24	7	7
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	0.021	0.011	-10000	0	-10000	0	0
GIT1	0.019	0.006	-10000	0	-0.11	1	1
GIT1/beta-PIX/PAK1	0.026	0.045	-10000	0	-0.15	29	29
Importin alpha/Importin beta/TPX2	-0.019	0.079	-10000	0	-0.19	89	89
PPP2R5D	0.018	0.013	-10000	0	-0.11	5	5
Aurora A/TPX2	-0.009	0.087	-10000	0	-0.18	85	85
PAK1	0.017	0.017	-10000	0	-0.11	9	9
CKAP5	0.004	0.066	-10000	0	-0.29	25	25

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.024	0.061	-10000	0	-0.14	53	53
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	0.018	0.01	-10000	0	-0.11	3	3
STAT1 (dimer)/Cbp/p300	0.026	0.083	-10000	0	-0.22	34	34
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.014	0.066	-10000	0	-0.17	54	54
antigen processing and presentation of peptide antigen via MHC class I	-0.047	0.091	-10000	0	-0.22	83	83
CaM/Ca2+	0.022	0.07	-10000	0	-0.17	44	44
RAP1A	0.018	0.019	-10000	0	-0.29	2	2
STAT1 (dimer)/SHP2	0.012	0.062	-10000	0	-0.2	19	19
AKT1	-0.012	0.1	-10000	0	-0.26	55	55
MAP2K1	0.013	0.057	-10000	0	-0.18	24	24
MAP3K11	0.012	0.055	-10000	0	-0.13	53	53
IFNGR1	0.014	0.035	-10000	0	-0.2	11	11
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.028	0.13	-10000	0	-0.29	81	81
Rap1/GTP	-0.01	0.032	-10000	0	-0.15	16	16
CRKL/C3G	0.028	0.007	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.033	0.06	-10000	0	-0.13	52	52
CEBPB	0.02	0.12	-10000	0	-0.42	24	24
STAT3	-0.003	0.079	-10000	0	-0.29	37	37
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.039	0.052	-10000	0	-10000	0	0
STAT1	0.006	0.059	-10000	0	-0.14	56	56
CALM1	0.007	0.056	-10000	0	-0.21	28	28
IFN-gamma (dimer)	0.017	0.012	-10000	0	-0.12	3	3
PIK3CA	-0.011	0.085	-10000	0	-0.22	65	65
STAT1 (dimer)/PIAS1	0.012	0.072	-10000	0	-0.24	26	26
CEBPB/PTGES2/Cbp/p300	-0.022	0.088	-10000	0	-0.32	31	31
mol:Ca2+	0.022	0.06	-10000	0	-0.14	53	53
MAPK3	0.024	0.065	-10000	0	-0.4	4	4
STAT1 (dimer)	-0.035	0.14	-10000	0	-0.31	81	81
MAPK1	0.005	0.15	-10000	0	-0.79	16	16
JAK2	0.013	0.028	-10000	0	-0.11	23	23
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
JAK1	0.013	0.04	-10000	0	-0.22	13	13
CAMK2D	0	0	-10000	0	-10000	0	0
DAPK1	0.026	0.091	-10000	0	-0.39	14	14
SMAD7	-0.007	0.064	-10000	0	-0.15	45	45
CBL/CRKL/C3G	0.031	0.053	-10000	0	-0.17	14	14
PI3K	-0.001	0.095	-10000	0	-0.21	62	62
IFNG	0.017	0.012	-10000	0	-0.12	3	3
apoptosis	0.021	0.075	0.21	3	-0.33	12	15
CAMK2G	0.007	0.047	-10000	0	-0.14	40	40
STAT3 (dimer)	-0.003	0.079	-10000	0	-0.29	37	37
CAMK2A	0.018	0.01	-10000	0	-0.11	3	3
CAMK2B	-0.047	0.11	-10000	0	-0.29	75	75
FRAP1	-0.008	0.094	-10000	0	-0.24	54	54
PRKCD	-0.009	0.087	-10000	0	-0.22	54	54
RAP1B	0	0	-10000	0	-10000	0	0
negative regulation of cell growth	-0.047	0.091	-10000	0	-0.22	83	83
PTPN2	0.018	0.013	-10000	0	-0.11	5	5
EP300	0.012	0.046	-10000	0	-0.24	15	15
IRF1	0.013	0.083	-10000	0	-0.27	27	27
STAT1 (dimer)/PIASy	0.013	0.059	-10000	0	-0.2	17	17
SOCS1	0.021	0.002	-10000	0	-10000	0	0
mol:GDP	0.028	0.05	-10000	0	-0.17	14	14
CASP1	-0.023	0.091	-10000	0	-0.2	95	95
PTGES2	0.019	0	-10000	0	-10000	0	0
IRF9	0.019	0.064	-10000	0	-0.19	31	31
mol:PI-3-4-5-P3	-0.01	0.088	-10000	0	-0.21	59	59
RAP1/GDP	0.018	0.043	-10000	0	-0.15	16	16
CBL	0.012	0.052	-10000	0	-0.13	53	53
MAP3K1	0.012	0.054	-10000	0	-0.14	40	40
PIAS1	0.008	0.056	-10000	0	-0.29	18	18
PIAS4	0.018	0.006	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.047	0.091	-10000	0	-0.22	83	83
PTPN11	0.008	0.054	-10000	0	-0.14	52	52
CREBBP	0.019	0.001	-10000	0	-10000	0	0
RAPGEF1	0.019	0	-10000	0	-10000	0	0

×

Signaling events mediated by PRL

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.01	0.033	-10000	0	-0.11	37	37
mol:Halofuginone	-0.001	0.034	-10000	0	-0.19	16	16
ITGA1	0	0	-10000	0	-10000	0	0
CDKN1A	-0.037	0.16	-10000	0	-0.4	76	76
PRL-3/alpha Tubulin	0.011	0.05	-10000	0	-0.19	24	24
mol:Ca2+	-0.023	0.088	0.29	12	-0.2	73	85
AGT	-0.035	0.11	-10000	0	-0.26	104	104
CCNA2	-0.012	0.13	-10000	0	-0.65	18	18
TUBA1B	0.018	0.013	-10000	0	-0.29	1	1
EGR1	0.001	0.074	-10000	0	-0.36	19	19
CDK2/Cyclin E1	-0.025	0.15	-10000	0	-0.36	76	76
MAPK3	0.005	0.047	-10000	0	-0.19	23	23
PRL-2 /Rab GGTase beta	0.022	0.039	-10000	0	-0.22	12	12
MAPK1	0	0.056	-10000	0	-0.19	36	36
PTP4A1	-0.003	0.13	-10000	0	-0.72	16	16
PTP4A3	-0.004	0.07	-10000	0	-0.18	63	63
PTP4A2	0.017	0.025	-10000	0	-0.2	6	6
ITGB1	0.005	0.047	-10000	0	-0.19	23	23
SRC	0.019	0	-10000	0	-10000	0	0
RAC1	-0.011	0.12	-10000	0	-0.39	44	44
Rab GGTase beta/Rab GGTase alpha	0.022	0.034	-10000	0	-0.19	11	11
PRL-1/ATF-5	-0.009	0.13	-10000	0	-0.67	16	16
RABGGTA	0.017	0.016	-10000	0	-0.11	8	8
BCAR1	0.006	0.062	0.28	23	-10000	0	23
RHOC	-0.014	0.13	-10000	0	-0.39	47	47
RHOA	-0.013	0.14	-10000	0	-0.44	41	41
cell motility	-0.015	0.13	-10000	0	-0.4	44	44
PRL-1/alpha Tubulin	-0.008	0.13	-10000	0	-0.67	16	16
PRL-3/alpha1 Integrin	-0.001	0.047	-10000	0	-0.12	63	63
ROCK1	-0.015	0.14	-10000	0	-0.4	44	44
RABGGTB	0.012	0.045	-10000	0	-0.25	14	14
CDK2	0.011	0.034	-10000	0	-0.12	29	29
mitosis	-0.003	0.13	-10000	0	-0.63	19	19
ATF5	0.018	0.01	-10000	0	-0.11	3	3

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.019	0	-9999	-10000	0	0
SPHK1	0.008	0.036	-9999	-0.11	45	45
GNAI2	0	0.073	-9999	-0.28	34	34
mol:S1P	0.016	0.016	-9999	-10000	0	0
GNAO1	-0.014	0.085	-9999	-0.2	81	81
mol:Sphinganine-1-P	0.014	0.023	-9999	-10000	0	0
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.021	0.045	-9999	-0.13	39	39
GNAI3	0.014	0.038	-9999	-0.29	8	8
G12/G13	0.009	0.059	-9999	-0.19	39	39
S1PR3	0	0	-9999	-10000	0	0
S1PR2	0	0	-9999	-10000	0	0
EDG1	0.001	0.067	-9999	-0.22	39	39
S1P1/S1P	0.019	0.033	-9999	-0.18	10	10
S1PR5	0	0	-9999	-10000	0	0
S1PR4	0	0	-9999	-10000	0	0
GNAI1	-0.047	0.11	-9999	-0.2	158	158
S1P/S1P5/G12	0.01	0.044	-9999	-0.14	39	39
S1P/S1P3/Gq	0.024	0.03	-9999	-0.18	8	8
S1P/S1P4/Gi	-0.038	0.12	-9999	-0.22	129	129
GNAQ	0.015	0.023	-9999	-0.11	17	17
GNAZ	-0.007	0.082	-9999	-0.24	55	55
GNA14	0.015	0.022	-9999	-0.11	15	15
GNA15	0.012	0.033	-9999	-0.12	26	26
GNA12	-0.005	0.082	-9999	-0.27	43	43
GNA13	0.016	0.021	-9999	-0.11	14	14
GNA11	0.003	0.068	-9999	-0.29	27	27
ABCC1	0.015	0.023	-9999	-0.11	17	17

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.008	0.056	-9999	-0.29	18	18
VLDLR	-0.02	0.092	-9999	-0.2	96	96
LRPAP1	0.013	0.043	-9999	-0.28	11	11
NUDC	0.01	0.053	-9999	-0.29	16	16
RELN/LRP8	0.021	0.045	-9999	-0.15	21	21
CaM/Ca2+	0.006	0.038	-9999	-0.2	16	16
KATNA1	0.012	0.045	-9999	-0.28	12	12
GO:0030286	0	0	-9999	-10000	0	0
ABL1	0.009	0.054	-9999	-0.2	25	25
IQGAP1/CaM	0.001	0.074	-9999	-0.2	57	57
DAB1	0.019	0.006	-9999	-0.11	1	1
IQGAP1	-0.008	0.086	-9999	-0.27	49	49
PLA2G7	0.007	0.038	-9999	-0.11	49	49
CALM1	0.007	0.056	-9999	-0.21	28	28
DYNLT1	0.012	0.045	-9999	-0.28	12	12
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	0.017	0.044	-9999	-0.2	16	16
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.012	0.036	-9999	-0.14	22	22
CDK5R1	0.014	0.025	-9999	-0.11	21	21
LIS1/Poliovirus Protein 3A	0.005	0.049	-9999	-0.2	26	26
CDK5R2	0.015	0.023	-9999	-0.11	17	17
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	0.007	0.061	-9999	-0.15	53	53
YWHAE	0.011	0.045	-9999	-0.21	19	19
NDEL1/14-3-3 E	0.01	0.09	-9999	-0.29	29	29
MAP1B	-0.022	0.082	-9999	-0.24	62	62
RAC1	-0.001	0.071	-9999	-0.29	18	18
p35/CDK5	0.004	0.072	-9999	-0.15	74	74
RELN	0.007	0.038	-9999	-0.11	50	50
PAFAH/LIS1	0.012	0.055	-9999	-0.2	26	26
LIS1/CLIP170	0.015	0.056	-9999	-0.2	28	28
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	0.006	0.1	-9999	-0.28	45	45
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.011	0.099	-9999	-0.22	81	81
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	0.002	0.086	-9999	-0.29	26	26
LIS1/IQGAP1	0.003	0.076	-9999	-0.19	61	61
RHOA	-0.001	0.076	-9999	-0.32	16	16
PAFAH1B1	0.013	0.039	-9999	-0.19	19	19
PAFAH1B3	-0.005	0.077	-9999	-0.22	55	55
PAFAH1B2	0.019	0	-9999	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	-0.004	0.093	-9999	-0.21	71	71
NDEL1/Katanin 60/Dynein heavy chain	0.014	0.098	-9999	-0.29	33	33
LRP8	0.009	0.043	-9999	-0.16	29	29
NDEL1/Katanin 60	0.01	0.09	-9999	-0.28	30	30
P39/CDK5	0.004	0.071	-9999	-0.15	72	72
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.014	0.07	-9999	-0.26	28	28
CDK5	0.008	0.059	-9999	-0.24	21	21
PPP2R5D	0.018	0.013	-9999	-0.11	5	5
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.013	0.047	-9999	-0.17	28	28
CSNK2A1	0.01	0.053	-9999	-0.29	16	16
RELN/VLDLR/DAB1/LIS1	0.012	0.07	-9999	-0.14	68	68
RELN/VLDLR	0.01	0.067	-9999	-0.14	66	66
CDC42	0.004	0.046	-9999	-0.18	14	14

×

IL4-mediated signaling events

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
BCL2L1	-0.081	0.36	-10000	0	-1	26	26
STAT6 (cleaved dimer)	-0.17	0.27	-10000	0	-0.86	49	49
IGHG1	-0.038	0.23	-10000	0	-0.62	38	38
IGHG3	-0.087	0.34	-10000	0	-0.87	42	42
AKT1	-0.035	0.26	-10000	0	-0.73	33	33
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	0.003	0.17	-10000	0	-0.48	17	17
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.031	0.25	-10000	0	-0.73	26	26
THY1	-0.16	0.5	-10000	0	-1.3	65	65
MYB	0.013	0.028	-10000	0	-0.11	26	26
HMGA1	0.016	0.019	-10000	0	-0.11	12	12
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.021	0.23	-10000	0	-0.54	31	31
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.026	0.24	-10000	0	-0.71	24	24
SP1	-0.001	0.05	-10000	0	-0.14	36	36
INPP5D	0	0	-10000	0	-10000	0	0
SOCS5	0.012	0.032	-10000	0	-0.21	6	6
STAT6 (dimer)/ETS1	-0.07	0.34	-10000	0	-0.91	38	38
SOCS1	-0.032	0.27	-10000	0	-0.66	35	35
SOCS3	-0.003	0.2	-10000	0	-0.65	3	3
FCER2	-0.05	0.29	-10000	0	-0.7	38	38
PARP14	0.002	0.001	-10000	0	-10000	0	0
CCL17	-0.079	0.35	-10000	0	-1	26	26
GRB2	0.014	0.039	-10000	0	-0.26	10	10
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.016	0.2	-10000	0	-0.61	22	22
T cell proliferation	-0.086	0.36	-10000	0	-0.97	40	40
IL4R/JAK1	-0.092	0.36	-10000	0	-0.96	40	40
EGR2	-0.14	0.48	-10000	0	-1.3	59	59
JAK2	0.013	0.048	-10000	0	-0.14	16	16
JAK3	0.023	0.004	-10000	0	-10000	0	0
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
JAK1	0.005	0.072	-10000	0	-0.26	34	34
COL1A2	-0.18	0.47	-10000	0	-1.2	81	81
CCL26	-0.087	0.35	-10000	0	-0.94	38	38
IL4R	-0.087	0.38	-10000	0	-1.1	30	30
PTPN6	0.005	0.057	-10000	0	-0.21	27	27
IL13RA2	-0.39	0.65	-10000	0	-1.2	203	203
IL13RA1	-0.007	0.091	-10000	0	-0.27	45	45
IRF4	0.029	0.098	-10000	0	-10000	0	0
ARG1	-0.003	0.16	-10000	0	-0.57	13	13
CBL	-0.018	0.22	-10000	0	-0.51	31	31
GTF3A	0.02	0.024	-10000	0	-0.17	4	4
PIK3CA	-0.011	0.085	-10000	0	-0.22	65	65
IL13RA1/JAK2	0.008	0.084	-10000	0	-0.18	52	52
IRF4/BCL6	0.018	0.1	-10000	0	-10000	0	0
CD40LG	0.028	0.001	-10000	0	-10000	0	0
MAPK14	-0.013	0.22	-10000	0	-0.54	21	21
mitosis	-0.031	0.25	-10000	0	-0.68	33	33
STAT6	-0.093	0.4	-10000	0	-1	38	38
SPI1	0.019	0.029	-10000	0	-10000	0	0
RPS6KB1	-0.026	0.24	-10000	0	-0.66	32	32
STAT6 (dimer)	-0.093	0.4	-10000	0	-1	38	38
STAT6 (dimer)/PARP14	-0.099	0.36	-10000	0	-0.98	38	38
mast cell activation	-0.001	0.014	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.008	0.2	-10000	0	-0.5	21	21
FRAP1	-0.035	0.26	-10000	0	-0.73	32	32
LTA	-0.079	0.36	-10000	0	-1.1	26	26
FES	0.017	0.016	-10000	0	-0.11	8	8
T-helper 1 cell differentiation	0.091	0.39	1	38	-10000	0	38
CCL11	-0.081	0.34	-10000	0	-1	28	28
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.004	0.2	-10000	0	-0.51	18	18
IL2RG	0.017	0.027	-10000	0	-0.11	24	24
IL10	-0.079	0.35	-10000	0	-1	28	28
IRS1	-0.003	0.071	-10000	0	-0.19	54	54
IRS2	-0.02	0.099	-10000	0	-0.25	78	78
IL4	0.013	0.12	-10000	0	-10000	0	0
IL5	-0.079	0.35	-10000	0	-1	26	26
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.076	0.34	-10000	0	-0.83	42	42
COL1A1	-0.019	0.21	-10000	0	-1.2	6	6
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.092	0.36	-10000	0	-1.1	30	30
IL2R gamma/JAK3	0.031	0.02	-10000	0	-10000	0	0
TFF3	-0.083	0.36	-10000	0	-1	29	29
ALOX15	-0.079	0.35	-10000	0	-1	26	26
MYBL1	-0.017	0.085	-10000	0	-0.18	93	93
T-helper 2 cell differentiation	-0.064	0.31	-10000	0	-0.77	42	42
SHC1	0.004	0.052	-10000	0	-0.14	48	48
CEBPB	0.002	0.077	-10000	0	-0.22	51	51
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.035	0.25	-10000	0	-0.68	33	33
mol:PI-3-4-5-P3	-0.035	0.26	-10000	0	-0.73	32	32
PI3K	-0.039	0.27	-10000	0	-0.79	32	32
DOK2	0	0	-10000	0	-10000	0	0
ETS1	0.016	0.018	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.014	0.2	-10000	0	-0.58	27	27
ITGB3	-0.079	0.36	-10000	0	-1	27	27
PIGR	-0.08	0.36	-10000	0	-1.1	26	26
IGHE	0.005	0.077	0.2	35	-0.19	22	57
MAPKKK cascade	-0.013	0.2	-10000	0	-0.57	27	27
BCL6	-0.008	0.082	-10000	0	-0.29	37	37
OPRM1	-0.079	0.35	-10000	0	-1	26	26
RETNLB	-0.087	0.35	-10000	0	-0.94	38	38
SELP	-0.08	0.36	-10000	0	-1.1	26	26
AICDA	-0.08	0.34	-10000	0	-1	26	26

×

Presenilin action in Notch and Wnt 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.033	0.16	-10000	0	-0.51	52	52
HDAC1	0.019	0.033	-10000	0	-0.2	8	8
AES	0.013	0.045	-10000	0	-0.22	16	16
FBXW11	0.011	0.047	-10000	0	-0.26	14	14
DTX1	0	0	-10000	0	-10000	0	0
LRP6/FZD1	0.021	0.026	-10000	0	-0.16	2	2
TLE1	0.017	0.026	-10000	0	-0.19	7	7
AP1	-0.025	0.099	-10000	0	-0.23	84	84
NCSTN	0.008	0.056	-10000	0	-0.26	20	20
ADAM10	0.008	0.036	-10000	0	-0.11	45	45
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.009	0.12	-10000	0	-0.46	16	16
NICD/RBPSUH	-0.024	0.16	-10000	0	-0.51	53	53
WIF1	-0.006	0.051	-10000	0	-0.11	100	100
NOTCH1	-0.033	0.17	-10000	0	-0.53	52	52
PSENEN	0.013	0.041	-10000	0	-0.27	10	10
KREMEN2	0.019	0.006	-10000	0	-0.11	1	1
DKK1	-0.018	0.059	-10000	0	-0.11	149	149
beta catenin/beta TrCP1	0.017	0.067	-10000	0	-0.31	14	14
APH1B	0.018	0.02	-10000	0	-0.29	2	2
APH1A	0.015	0.036	-10000	0	-0.27	8	8
AXIN1	-0.004	0.057	0.19	9	-0.18	40	49
CtBP/CBP/TCF1/TLE1/AES	0.034	0.071	0.26	9	-0.32	5	14
PSEN1	0.011	0.047	-10000	0	-0.26	15	15
FOS	-0.046	0.12	-10000	0	-0.22	146	146
JUN	-0.002	0.077	-10000	0	-0.28	37	37
MAP3K7	0.011	0.049	-10000	0	-0.22	19	19
CTNNB1	0.009	0.06	-10000	0	-0.28	12	12
MAPK3	0.019	0.006	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.031	0.026	-10000	0	-0.13	2	2
HNF1A	0.02	0.005	-10000	0	-10000	0	0
CTBP1	0.01	0.054	-10000	0	-0.29	17	17
MYC	-0.12	0.39	-10000	0	-1.3	53	53
NKD1	0	0.002	-10000	0	-10000	0	0
FZD1	0.015	0.023	-10000	0	-0.11	17	17
NOTCH1 precursor/Deltex homolog 1	-0.033	0.16	-10000	0	-0.5	52	52
apoptosis	-0.025	0.099	-10000	0	-0.23	84	84
Delta 1/NOTCHprecursor	-0.033	0.16	-10000	0	-0.5	52	52
DLL1	0	0	-10000	0	-10000	0	0
PPARD	0.008	0.033	-10000	0	-10000	0	0
Gamma Secretase	0.04	0.063	-10000	0	-0.18	33	33
APC	-0.039	0.17	0.18	10	-0.45	55	65
DVL1	0.007	0.1	-10000	0	-0.45	22	22
CSNK2A1	0.009	0.053	-10000	0	-0.29	16	16
MAP3K7IP1	0.021	0.007	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	0.011	0.041	-10000	0	-0.12	6	6
LRP6	0.013	0.029	-10000	0	-0.12	23	23
CSNK1A1	0.014	0.038	-10000	0	-0.29	8	8
NLK	0.012	0.064	-10000	0	-0.25	25	25
CCND1	-0.095	0.33	-10000	0	-1.3	38	38
WNT1	0.019	0.006	-10000	0	-0.11	1	1
Axin1/APC/beta catenin	-0.01	0.13	0.2	3	-0.37	48	51
DKK2	0.013	0.028	-10000	0	-0.11	25	25
NOTCH1 precursor/DVL1	-0.023	0.19	-10000	0	-0.51	60	60
GSK3B	0.004	0.066	-10000	0	-0.26	29	29
FRAT1	0.016	0.023	-10000	0	-0.12	12	12
NOTCH/Deltex homolog 1	-0.033	0.16	-10000	0	-0.51	52	52
PPP2R5D	0.014	0.041	-10000	0	-0.23	9	9
MAPK1	0.009	0.051	-10000	0	-0.22	22	22
WNT1/LRP6/FZD1	0.027	0.039	-10000	0	-0.14	2	2
RBPJ	0.012	0.041	-10000	0	-0.29	8	8
CREBBP	0.018	0.008	-10000	0	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	-0.031	0.22	-10000	0	-0.88	31	31
regulation of axonogenesis	-0.012	0.041	0.15	30	-10000	0	30
myoblast fusion	0.005	0.098	0.38	31	-10000	0	31
mol:GTP	-0.001	0.056	-10000	0	-0.22	31	31
regulation of calcium-dependent cell-cell adhesion	-0.004	0.068	0.19	53	-10000	0	53
ARF1/GTP	0.01	0.05	-10000	0	-0.16	36	36
mol:GM1	-0.002	0.041	-10000	0	-0.16	31	31
mol:Choline	0.012	0.037	-10000	0	-0.13	30	30
lamellipodium assembly	-0.006	0.11	-10000	0	-0.42	31	31
MAPK3	0.003	0.08	-10000	0	-0.3	31	31
ARF6/GTP/NME1/Tiam1	0.004	0.068	-10000	0	-0.19	53	53
ARF1	0.014	0.036	-10000	0	-0.25	9	9
ARF6/GDP	-0.005	0.098	-10000	0	-0.39	31	31
ARF1/GDP	0.003	0.094	-10000	0	-0.35	33	33
ARF6	0.01	0.033	-10000	0	-0.12	31	31
RAB11A	0.016	0.033	-10000	0	-0.29	6	6
TIAM1	0.001	0.067	-10000	0	-0.23	36	36
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.001	0.082	-10000	0	-0.31	32	32
actin filament bundle formation	-0.001	0.095	0.35	33	-10000	0	33
KALRN	-0.001	0.075	-10000	0	-0.29	31	31
RAB11FIP3/RAB11A	0.021	0.039	-10000	0	-0.22	12	12
RhoA/GDP	0.001	0.096	-10000	0	-0.36	33	33
NME1	-0.001	0.008	-10000	0	-10000	0	0
Rac1/GDP	0.001	0.094	-10000	0	-0.35	32	32
substrate adhesion-dependent cell spreading	-0.001	0.056	-10000	0	-0.22	31	31
cortical actin cytoskeleton organization	-0.006	0.11	-10000	0	-0.42	31	31
RAC1	0.015	0.035	-10000	0	-0.29	7	7
liver development	-0.001	0.056	-10000	0	-0.22	31	31
ARF6/GTP	-0.001	0.056	-10000	0	-0.22	31	31
RhoA/GTP	0.011	0.051	-10000	0	-0.17	35	35
mol:GDP	-0.006	0.098	-10000	0	-0.39	31	31
ARF6/GTP/RAB11FIP3/RAB11A	0.019	0.052	-10000	0	-0.14	41	41
RHOA	0.015	0.035	-10000	0	-0.29	7	7
PLD1	0.008	0.043	-10000	0	-0.16	31	31
RAB11FIP3	0.013	0.041	-10000	0	-0.21	15	15
tube morphogenesis	-0.006	0.11	-10000	0	-0.42	31	31
ruffle organization	0.012	0.041	-10000	0	-0.15	30	30
regulation of epithelial cell migration	-0.001	0.056	-10000	0	-0.22	31	31
PLD2	0.009	0.043	-10000	0	-0.15	31	31
PIP5K1A	0.012	0.041	-10000	0	-0.15	30	30
mol:Phosphatidic acid	0.012	0.037	-10000	0	-0.13	30	30
Rac1/GTP	-0.006	0.11	-10000	0	-0.42	31	31

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.028	0.031	-10000	0	-0.12	21	21
ER alpha/Gai/GDP/Gbeta gamma	-0.037	0.18	-10000	0	-0.41	72	72
AKT1	-0.038	0.19	-10000	0	-0.58	45	45
PIK3CA	-0.011	0.085	-10000	0	-0.22	65	65
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.035	0.19	-10000	0	-0.6	43	43
mol:Ca2+	0.024	0.039	-10000	0	-0.16	2	2
IGF1R	-0.001	0.07	-10000	0	-0.21	46	46
E2/ER alpha (dimer)/Striatin	0.026	0	-10000	0	-10000	0	0
SHC1	0.004	0.052	-10000	0	-0.14	48	48
apoptosis	0.035	0.18	0.56	45	-10000	0	45
RhoA/GTP	-0.017	0.049	-10000	0	-0.25	14	14
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.051	0.13	-10000	0	-0.38	51	51
regulation of stress fiber formation	-0.008	0.06	0.2	29	-10000	0	29
E2/ERA-ERB (dimer)	0.026	0	-10000	0	-10000	0	0
KRAS	0.011	0.048	-10000	0	-0.28	14	14
G13/GTP	0.023	0.011	-10000	0	-10000	0	0
pseudopodium formation	0.008	0.06	-10000	0	-0.2	29	29
E2/ER alpha (dimer)/PELP1	0.023	0.021	-10000	0	-0.16	7	7
GRB2	0.014	0.039	-10000	0	-0.26	10	10
GNG2	0	0	-10000	0	-10000	0	0
GNAO1	-0.014	0.085	-10000	0	-0.2	81	81
HRAS	0.009	0.055	-10000	0	-0.28	18	18
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.024	0.13	-10000	0	-0.36	53	53
E2/ER beta (dimer)	0.014	0	-10000	0	-10000	0	0
mol:GDP	0.016	0.033	-10000	0	-0.13	12	12
mol:NADP	-0.024	0.13	-10000	0	-0.36	53	53
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
mol:IP3	0.024	0.039	-10000	0	-0.16	2	2
IGF-1R heterotetramer	-0.001	0.069	-10000	0	-0.21	46	46
PLCB1	0.021	0.041	-10000	0	-0.17	2	2
PLCB2	0.023	0.04	-10000	0	-0.17	2	2
IGF1	0.014	0.025	-10000	0	-0.11	21	21
mol:L-citrulline	-0.024	0.13	-10000	0	-0.36	53	53
RHOA	0.015	0.035	-10000	0	-0.29	7	7
Gai/GDP	-0.083	0.24	-10000	0	-0.7	64	64
JNK cascade	0.014	0	-10000	0	-10000	0	0
BCAR1	0	0	-10000	0	-10000	0	0
ESR2	0.019	0	-10000	0	-10000	0	0
GNAQ	0.015	0.023	-10000	0	-0.11	17	17
ESR1	0.019	0	-10000	0	-10000	0	0
Gq family/GDP/Gbeta gamma	-0.004	0.15	-10000	0	-0.51	36	36
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.004	0.14	-10000	0	-0.73	16	16
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.026	0.14	-10000	0	-0.37	56	56
GNAZ	-0.007	0.082	-10000	0	-0.24	55	55
E2/ER alpha (dimer)	0.014	0	-10000	0	-10000	0	0
STRN	0.019	0	-10000	0	-10000	0	0
GNAL	0.018	0.01	-10000	0	-0.11	3	3
PELP1	0.015	0.035	-10000	0	-0.29	7	7
MAPK11	0.018	0	-10000	0	-10000	0	0
GNAI2	0	0.073	-10000	0	-0.28	34	34
GNAI3	0.014	0.038	-10000	0	-0.29	8	8
GNAI1	-0.047	0.11	-10000	0	-0.2	158	158
HBEGF	-0.068	0.16	-10000	0	-0.4	75	75
cAMP biosynthetic process	0.022	0.004	-10000	0	-10000	0	0
SRC	-0.042	0.17	-10000	0	-0.39	72	72
PI3K	-0.015	0.092	-10000	0	-0.21	87	87
GNB1	0.007	0.061	-10000	0	-0.29	21	21
G13/GDP/Gbeta gamma	0.019	0.045	-10000	0	-0.18	14	14
SOS1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.051	0.11	-10000	0	-0.29	65	65
Gs family/GTP	0.028	0.005	-10000	0	-10000	0	0
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.011	0.068	-10000	0	-0.17	59	59
vasodilation	-0.023	0.13	-10000	0	-0.35	53	53
mol:DAG	0.024	0.039	-10000	0	-0.16	2	2
Gs family/GDP/Gbeta gamma	-0.01	0.032	-10000	0	-0.19	10	10
MSN	0.008	0.064	-10000	0	-0.22	28	28
Gq family/GTP	0.021	0.042	-10000	0	-0.19	2	2
mol:PI-3-4-5-P3	-0.034	0.18	-10000	0	-0.58	43	43
NRAS	-0.01	0.086	-10000	0	-0.29	42	42
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.023	0.13	0.35	53	-10000	0	53
GRB2/SOS1	0.011	0.026	-10000	0	-0.17	10	10
RhoA/GDP	0.024	0.04	-10000	0	-0.22	4	4
NOS3	-0.026	0.14	-10000	0	-0.38	53	53
GNA11	0.003	0.068	-10000	0	-0.29	27	27
MAPKKK cascade	-0.001	0.11	-10000	0	-0.41	20	20
E2/ER alpha (dimer)/PELP1/Src	-0.027	0.14	-10000	0	-0.4	51	51
ruffle organization	0.008	0.06	-10000	0	-0.2	29	29
ROCK2	0.012	0.056	-10000	0	-0.22	15	15
GNA14	0.015	0.022	-10000	0	-0.11	15	15
GNA15	0.012	0.033	-10000	0	-0.12	26	26
GNA13	0.016	0.021	-10000	0	-0.11	14	14
MMP9	-0.07	0.16	-10000	0	-0.37	90	90
MMP2	-0.05	0.17	-10000	0	-0.41	73	73

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.031	0.031	-9999	-0.14	15	15
VEGFR1 homodimer/NRP1	0.018	0.027	-9999	-0.15	12	12
mol:DAG	0.025	0.029	-9999	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	-0.016	0.073	-9999	-0.14	118	118
CaM/Ca2+	0.027	0.044	-9999	-0.23	5	5
HIF1A	0.021	0.047	-9999	-0.28	12	12
GAB1	0.003	0.056	-9999	-0.15	50	50
AKT1	-0.005	0.1	-9999	-0.32	36	36
PLCG1	0.025	0.03	-9999	-10000	0	0
NOS3	0.02	0.072	-9999	-0.28	21	21
CBL	0.019	0	-9999	-10000	0	0
mol:NO	0.02	0.07	-9999	-0.27	21	21
FLT1	0.025	0.033	-9999	-0.18	12	12
PGF	0.009	0.036	-9999	-0.12	39	39
VEGFR1 homodimer/NRP2/VEGFR121	-0.006	0.077	-9999	-0.26	9	9
CALM1	0.007	0.056	-9999	-0.21	28	28
PIK3CA	-0.011	0.085	-9999	-0.22	65	65
eNOS/Hsp90	0.029	0.073	-9999	-0.27	21	21
endothelial cell proliferation	0.021	0.04	-9999	-0.25	4	4
mol:Ca2+	0.025	0.029	-9999	-10000	0	0
MAPK3	0.027	0.025	-9999	-10000	0	0
MAPK1	0.025	0.029	-9999	-0.23	2	2
PIK3R1	-0.015	0.095	-9999	-0.27	62	62
PLGF homodimer	0.009	0.036	-9999	-0.12	39	39
PRKACA	0.019	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.071	0.13	-9999	-0.22	197	197
VEGFA homodimer	-0.067	0.13	-9999	-0.22	188	188
VEGFR1 homodimer/VEGFA homodimer	-0.018	0.082	-9999	-0.16	122	122
platelet activating factor biosynthetic process	0.027	0.028	-9999	-0.22	2	2
PI3K	0.013	0.08	-9999	-0.24	23	23
PRKCA	0.025	0.027	-9999	-10000	0	0
PRKCB	0.019	0.026	-9999	-10000	0	0
VEGFR1 homodimer/PLGF homodimer	0.026	0.034	-9999	-0.14	13	13
VEGFA	-0.068	0.13	-9999	-0.22	188	188
VEGFB	0.017	0.023	-9999	-0.29	3	3
mol:IP3	0.025	0.029	-9999	-10000	0	0
RASA1	0.026	0.04	-9999	-0.27	7	7
NRP2	0.017	0.015	-9999	-0.11	7	7
VEGFR1 homodimer	0.025	0.033	-9999	-0.18	12	12
VEGFB homodimer	0.017	0.023	-9999	-0.29	3	3
NCK1	0.014	0.036	-9999	-0.19	14	14
eNOS/Caveolin-1	0.009	0.087	-9999	-0.32	25	25
PTPN11	0.015	0.033	-9999	-0.26	7	7
mol:PI-3-4-5-P3	0.012	0.079	-9999	-0.24	23	23
mol:L-citrulline	0.02	0.07	-9999	-0.27	21	21
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.003	0.081	-9999	-0.22	18	18
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.008	0.081	-9999	-0.25	14	14
CD2AP	0.003	0.061	-9999	-0.19	39	39
PI3K/GAB1	0.017	0.083	-9999	-0.23	31	31
PDPK1	0.005	0.069	-9999	-0.22	23	23
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.007	0.081	-9999	-0.29	11	11
mol:NADP	0.02	0.07	-9999	-0.27	21	21
HSP90AA1	0.018	0.019	-9999	-0.29	2	2
ubiquitin-dependent protein catabolic process	-0.004	0.08	-9999	-0.22	18	18
VEGFR1 homodimer/NRP2	0.031	0.029	-9999	-0.14	12	12

×

p75(NTR)-mediated signaling

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
Sortilin/TRAF6	0.025	0.026	-10000	0	-0.19	7	7
Necdin/E2F1	-0.059	0.096	-10000	0	-0.19	168	168
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.025	0.048	-10000	0	-0.14	24	24
NGF (dimer)/p75(NTR)/BEX1	-0.023	0.073	-10000	0	-0.15	112	112
NT-4/5 (dimer)/p75(NTR)	0.003	0.029	-10000	0	-0.07	70	70
IKBKB	0.019	0	-10000	0	-10000	0	0
AKT1	-0.016	0.079	-10000	0	-0.16	94	94
IKBKG	0.019	0	-10000	0	-10000	0	0
BDNF	0.004	0.042	-10000	0	-0.11	61	61
MGDIs/NGR/p75(NTR)/LINGO1	0.004	0.023	-10000	0	-10000	0	0
FURIN	0.018	0.01	-10000	0	-0.11	3	3
proBDNF (dimer)/p75(NTR)/Sortilin	0.017	0.043	-10000	0	-0.12	20	20
LINGO1	0	0	-10000	0	-10000	0	0
Sortilin/TRAF6/NRIF	-0.016	0.058	-10000	0	-0.3	15	15
proBDNF (dimer)	0.004	0.042	-10000	0	-0.11	61	61
NTRK1	0.018	0.011	-10000	0	-0.11	4	4
RTN4R	0	0	-10000	0	-10000	0	0
neuron apoptosis	-0.006	0.12	-10000	0	-0.38	34	34
IRAK1	0.008	0.057	-10000	0	-0.27	20	20
SHC1	0.004	0.029	-10000	0	-0.11	6	6
ARHGDIA	0.015	0.022	-10000	0	-0.11	16	16
RhoA/GTP	0.011	0.024	-10000	0	-0.2	7	7
Gamma Secretase	0.041	0.063	-10000	0	-0.17	33	33
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.005	0.06	-10000	0	-0.14	68	68
MAGEH1	-0.018	0.097	-10000	0	-0.25	71	71
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.043	0.078	-10000	0	-0.14	188	188
Mammalian IAPs/DIABLO	0.023	0.038	-10000	0	-0.2	7	7
proNGF (dimer)	0	0	-10000	0	-10000	0	0
MAGED1	0.004	0.066	-10000	0	-0.28	26	26
APP	0.013	0.042	-10000	0	-0.29	10	10
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
ZNF274	0	0.072	-10000	0	-0.26	36	36
RhoA/GDP/RHOGDI	0.018	0.031	-10000	0	-0.11	14	14
NGF	0	0	-10000	0	-10000	0	0
cell cycle arrest	0.023	0.047	0.11	96	-0.1	12	108
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.006	0.067	-10000	0	-0.19	46	46
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.015	0.028	-10000	0	-0.16	2	2
NCSTN	0.008	0.055	-10000	0	-0.26	20	20
mol:GTP	0.003	0.05	-10000	0	-0.16	35	35
PSENEN	0.014	0.041	-10000	0	-0.27	10	10
mol:ceramide	0.013	0.027	-10000	0	-0.13	7	7
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.01	0.061	-10000	0	-0.3	12	12
p75(NTR)/beta APP	0.012	0.042	-10000	0	-0.19	10	10
BEX1	-0.048	0.12	-10000	0	-0.26	126	126
mol:GDP	-0.001	0.021	-10000	0	-10000	0	0
NGF (dimer)	0.017	0.034	-10000	0	-0.093	1	1
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.014	0.027	-10000	0	-0.098	7	7
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
RAC1/GTP	0.012	0.027	-10000	0	-0.13	7	7
MYD88	0	0.075	-10000	0	-0.29	33	33
CHUK	0.016	0.024	-10000	0	-0.15	9	9
NGF (dimer)/p75(NTR)/PKA	0.004	0.05	-10000	0	-0.16	35	35
RHOB	-0.012	0.087	-10000	0	-0.23	66	66
RHOA	0.015	0.035	-10000	0	-0.29	7	7
MAGE-G1/E2F1	0.014	0.004	-10000	0	-0.07	1	1
NT3 (dimer)	0.018	0.01	-10000	0	-0.11	3	3
TP53	0.004	0.054	-10000	0	-0.14	41	41
PRDM4	0.013	0.027	-10000	0	-0.13	7	7
BDNF (dimer)	0.017	0.045	-10000	0	-0.14	4	4
PIK3CA	-0.011	0.085	-10000	0	-0.22	65	65
SORT1	0.016	0.031	-10000	0	-0.24	7	7
activation of caspase activity	0.022	0.046	-10000	0	-0.14	24	24
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.024	0.033	-10000	0	-0.13	9	9
RHOC	0.012	0.045	-10000	0	-0.28	12	12
XIAP	0	0	-10000	0	-10000	0	0
MAPK10	-0.004	0.099	-10000	0	-0.28	44	44
DIABLO	0.016	0.027	-10000	0	-0.26	5	5
SMPD2	0.013	0.027	-10000	0	-0.13	7	7
APH1B	0.018	0.02	-10000	0	-0.29	2	2
APH1A	0.015	0.036	-10000	0	-0.27	8	8
proNGF (dimer)/p75(NTR)/Sortilin	0.014	0.032	-10000	0	-0.15	7	7
PSEN1	0.011	0.047	-10000	0	-0.26	15	15
APAF-1/Pro-Caspase 9	0.025	0.021	-10000	0	-0.19	2	2
NT3 (dimer)/p75(NTR)	0.016	0.032	-10000	0	-0.14	1	1
MAPK8	0.016	0.059	-10000	0	-0.24	16	16
MAPK9	0.015	0.065	-10000	0	-0.26	18	18
APAF1	0.019	0	-10000	0	-10000	0	0
NTF3	0.018	0.01	-10000	0	-0.11	3	3
NTF4	0	0	-10000	0	-10000	0	0
NDN	-0.1	0.14	-10000	0	-0.22	269	269
RAC1/GDP	0.011	0.024	-10000	0	-0.2	7	7
RhoA-B-C/GDP	0.005	0.075	-10000	0	-0.17	65	65
p75 CTF/Sortilin/TRAF6/NRIF	0.035	0.048	-10000	0	-0.14	35	35
RhoA-B-C/GTP	0.003	0.049	-10000	0	-0.15	35	35
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.024	0.057	-10000	0	-0.13	35	35
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.027	0.044	-10000	0	-0.15	7	7
PRKACB	-0.002	0.076	-10000	0	-0.26	39	39
proBDNF (dimer)/p75 ECD	0.017	0.032	-10000	0	-0.14	3	3
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.001	0.048	-10000	0	-0.11	78	78
BIRC2	0.016	0.03	-10000	0	-0.29	5	5
neuron projection morphogenesis	-0.032	0.074	0.12	31	-0.17	62	93
BAD	0.01	0.079	-10000	0	-0.26	28	28
RIPK2	0.017	0.021	-10000	0	-0.18	5	5
NGFR	0.002	0.044	-10000	0	-0.11	70	70
CYCS	0.01	0.042	-10000	0	-0.14	28	28
ADAM17	0.017	0.015	-10000	0	-0.11	7	7
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.025	0.03	-10000	0	-0.14	4	4
BCL2L11	0.011	0.078	-10000	0	-0.26	27	27
BDNF (dimer)/p75(NTR)	0.006	0.043	-10000	0	-0.14	13	13
PI3K	-0.007	0.074	-10000	0	-0.15	93	93
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.014	0.029	-10000	0	-0.14	7	7
NDNL2	0	0	-10000	0	-10000	0	0
YWHAE	0.011	0.045	-10000	0	-0.21	19	19
PRKCI	0.015	0.028	-10000	0	-0.14	15	15
NGF (dimer)/p75(NTR)	0.003	0.029	-10000	0	-0.07	70	70
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.017	0.048	-10000	0	-0.14	30	30
TRAF6	0.018	0.019	-10000	0	-0.29	2	2
RAC1	0.015	0.035	-10000	0	-0.29	7	7
PRKCZ	0	0	-10000	0	-10000	0	0
PLG	0.019	0	-10000	0	-10000	0	0
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	0.012	0.035	-10000	0	-0.18	6	6
SQSTM1	0.004	0.062	-10000	0	-0.29	20	20
NGFRAP1	0.011	0.048	-10000	0	-0.29	13	13
CASP3	0.01	0.078	-10000	0	-0.26	27	27
E2F1	0.019	0.006	-10000	0	-0.11	1	1
CASP9	0.014	0.029	-10000	0	-0.13	18	18
IKK complex	0.031	0.054	-10000	0	-0.27	10	10
NGF (dimer)/TRKA	0.014	0.007	-10000	0	-0.07	4	4
MMP7	-0.014	0.057	-10000	0	-0.11	134	134
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.023	0.049	-10000	0	-0.13	35	35
MMP3	0.015	0.022	-10000	0	-0.11	15	15
APAF-1/Caspase 9	-0.01	0.037	-10000	0	-0.16	20	20

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.027	0.017	-9999	-0.26	1	1
CRKL	0.018	0.01	-9999	-0.11	3	3
Rac1/GDP	0.011	0.024	-9999	-0.2	7	7
DOCK1	0.011	0.046	-9999	-0.22	18	18
ITGA4	0.016	0.019	-9999	-0.11	12	12
alpha4/beta7 Integrin/MAdCAM1	0.044	0.025	-9999	-0.13	7	7
EPO	0.019	0	-9999	-10000	0	0
alpha4/beta7 Integrin	0.026	0.016	-9999	-0.14	2	2
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.009	0.053	-9999	-0.28	17	17
alpha4/beta1 Integrin	0.026	0.014	-9999	-10000	0	0
EPO/EPOR (dimer)	0.028	0	-9999	-10000	0	0
lamellipodium assembly	-0.011	0.1	-9999	-0.33	23	23
PIK3CA	-0.011	0.085	-9999	-0.22	65	65
PI3K	-0.015	0.092	-9999	-0.21	87	87
ARF6	0.018	0.015	-9999	-0.2	2	2
JAK2	0.031	0.015	-9999	-10000	0	0
PXN	0.018	0.011	-9999	-0.11	4	4
PIK3R1	-0.015	0.095	-9999	-0.27	62	62
MADCAM1	0.019	0.006	-9999	-0.11	1	1
cell adhesion	0.043	0.025	-9999	-0.13	7	7
CRKL/CBL	0.028	0.007	-9999	-10000	0	0
ITGB1	0.019	0	-9999	-10000	0	0
SRC	-0.021	0.069	-9999	-0.13	139	139
ITGB7	0.018	0.01	-9999	-0.11	3	3
RAC1	0.015	0.035	-9999	-0.29	7	7
alpha4/beta1 Integrin/VCAM1	-0.023	0.083	-9999	-0.15	143	143
p130Cas/Crk/Dock1	-0.011	0.074	-9999	-0.21	21	21
VCAM1	-0.078	0.13	-9999	-0.24	201	201
RHOA	0.015	0.035	-9999	-0.29	7	7
alpha4/beta1 Integrin/Paxillin/GIT1	0.047	0.015	-9999	-10000	0	0
BCAR1	-0.023	0.062	-9999	-0.12	139	139
EPOR	0.019	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.019	0	-9999	-10000	0	0
GIT1	0.019	0.006	-9999	-0.11	1	1
Rac1/GTP	-0.012	0.1	-9999	-0.35	22	22

×

BMP receptor signaling

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
BMP7/BMPR2/BMPR1A-1B/FS	0.041	0.041	-9999	-0.12	18	18
SMAD6-7/SMURF1	0.034	0.022	-9999	-0.15	3	3
NOG	0	0	-9999	-10000	0	0
SMAD9	0.017	0.046	-9999	-0.49	3	3
SMAD4	-0.004	0.079	-9999	-0.29	36	36
SMAD5	0.007	0.082	-9999	-0.3	27	27
BMP7/USAG1	0.022	0.024	-9999	-10000	0	0
SMAD5/SKI	0.017	0.08	-9999	-0.28	27	27
SMAD1	-0.013	0.16	-9999	-0.41	56	56
BMP2	-0.02	0.089	-9999	-0.18	101	101
SMAD1/SMAD1/SMAD4	-0.038	0.12	-9999	-0.42	37	37
BMPR1A	0.011	0.045	-9999	-0.22	17	17
BMPR1B	0.018	0.011	-9999	-0.11	4	4
BMPR1A-1B/BAMBI	-0.01	0.075	-9999	-0.15	96	96
AHSG	0.019	0.008	-9999	-0.11	2	2
CER1	0.019	0	-9999	-10000	0	0
BMP2-4/CER1	0.011	0.057	-9999	-0.15	45	45
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	0.002	0.077	-9999	-0.24	26	26
BMP2-4 (homodimer)	-0.003	0.065	-9999	-0.19	45	45
RGMB	0	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	0.038	0.039	-9999	-0.13	21	21
RGMA	0	0	-9999	-10000	0	0
SMURF1	0.019	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	0.001	0.054	-9999	-0.14	55	55
BMP2-4/USAG1	0.007	0.062	-9999	-0.15	54	54
SMAD6/SMURF1/SMAD5	0.017	0.08	-9999	-0.28	27	27
SOSTDC1	0.011	0.031	-9999	-0.11	32	32
BMP7/BMPR2/BMPR1A-1B	0.04	0.036	-9999	-0.13	18	18
SKI	0.019	0	-9999	-10000	0	0
BMP6 (homodimer)	0.014	0.025	-9999	-0.11	20	20
HFE2	0	0	-9999	-10000	0	0
ZFYVE16	0.004	0.063	-9999	-0.25	29	29
MAP3K7	0.006	0.059	-9999	-0.24	26	26
BMP2-4/CHRD	0.011	0.057	-9999	-0.15	45	45
SMAD5/SMAD5/SMAD4	0.012	0.091	-9999	-0.3	31	31
MAPK1	0.009	0.051	-9999	-0.22	22	22
TAK1/TAB family	0.025	0.072	-9999	-0.22	23	23
BMP7 (homodimer)	0.017	0.015	-9999	-0.11	7	7
NUP214	0.019	0	-9999	-10000	0	0
BMP6/FETUA	0.025	0.019	-9999	-0.14	1	1
SMAD1/SKI	-0.001	0.15	-9999	-0.38	56	56
SMAD6	0.019	0	-9999	-10000	0	0
CTDSP2	0.004	0.052	-9999	-0.14	50	50
BMP2-4/FETUA	0.011	0.058	-9999	-0.15	47	47
MAP3K7IP1	0.019	0	-9999	-10000	0	0
GREM1	0.006	0.039	-9999	-0.11	52	52
BMPR2 (homodimer)	0.014	0.039	-9999	-0.26	10	10
GADD34/PP1CA	0.02	0.055	-9999	-0.16	36	36
BMPR1A-1B (homodimer)	0.022	0.032	-9999	-0.19	10	10
CHRDL1	0	0	-9999	-10000	0	0
ENDOFIN/SMAD1	-0.006	0.16	-9999	-0.41	56	56
SMAD6-7/SMURF1/SMAD1	0.013	0.15	-9999	-0.45	35	35
SMAD6/SMURF1	0.019	0	-9999	-10000	0	0
BAMBI	-0.051	0.12	-9999	-0.2	167	167
SMURF2	0.011	0.047	-9999	-0.26	15	15
BMP2-4/CHRDL1	0	0.055	-9999	-0.16	45	45
BMP2-4/GREM1	0.003	0.062	-9999	-0.15	52	52
SMAD7	0.011	0.035	-9999	-0.29	3	3
SMAD8A/SMAD8A/SMAD4	0.021	0.057	-9999	-0.28	12	12
SMAD1/SMAD6	-0.001	0.15	-9999	-0.38	56	56
TAK1/SMAD6	0.019	0.042	-9999	-0.19	19	19
BMP7	0.017	0.015	-9999	-0.11	7	7
BMP6	0.014	0.025	-9999	-0.11	20	20
MAP3K7IP2	0.008	0.057	-9999	-0.27	20	20
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	0.007	0.057	-9999	-0.21	14	14
PPM1A	0.017	0.023	-9999	-0.29	3	3
SMAD1/SMURF2	-0.004	0.16	-9999	-0.41	56	56
SMAD7/SMURF1	0.023	0.025	-9999	-0.19	3	3
CTDSPL	0.019	0.006	-9999	-0.11	1	1
PPP1CA	0.009	0.055	-9999	-0.29	17	17
XIAP	0	0	-9999	-10000	0	0
CTDSP1	0.011	0.049	-9999	-0.27	15	15
PPP1R15A	0.013	0.028	-9999	-0.11	25	25
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	0.003	0.055	-9999	-0.14	55	55
CHRD	0.019	0	-9999	-10000	0	0
BMPR2	0.014	0.039	-9999	-0.26	10	10
BMP2-4/BMPR2/BMPR1A-1B/RGM	0	0.06	-9999	-0.16	55	55
BMP4	0.013	0.028	-9999	-0.11	25	25
FST	0.007	0.037	-9999	-0.11	47	47
BMP2-4/NOG	0	0.055	-9999	-0.16	45	45
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	0.048	0.035	-9999	-0.12	18	18

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.025	0.093	-10000	0	-0.37	5	5
CRKL	0.021	0.048	-10000	0	-0.17	8	8
mol:DAG	0.011	0.09	-10000	0	-0.21	58	58
HRAS	0.015	0.067	-10000	0	-0.21	27	27
MAPK8	0.012	0.054	-10000	0	-0.14	57	57
RAP1A	0.021	0.05	-10000	0	-0.18	10	10
GAB1	0.016	0.053	-10000	0	-0.19	12	12
MAPK14	0.011	0.054	-10000	0	-0.14	57	57
EPO	0.02	0.006	-10000	0	-10000	0	0
PLCG1	0.011	0.091	-10000	0	-0.22	58	58
EPOR/TRPC2/IP3 Receptors	0.02	0.006	-10000	0	-10000	0	0
RAPGEF1	0.019	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.04	0.009	-10000	0	-10000	0	0
GAB1/SHC/GRB2/SOS1	0.018	0.064	-10000	0	-0.2	24	24
EPO/EPOR (dimer)	0.029	0.013	-10000	0	-10000	0	0
IRS2	0.011	0.068	-10000	0	-0.21	32	32
STAT1	0.015	0.094	-10000	0	-0.3	25	25
STAT5B	0.015	0.09	-10000	0	-0.21	57	57
cell proliferation	0.013	0.049	-10000	0	-0.12	57	57
GAB1/SHIP/PIK3R1/SHP2/SHC	0.002	0.075	-10000	0	-0.2	43	43
TEC	0.021	0.048	-10000	0	-0.17	8	8
SOCS3	0.019	0	-10000	0	-10000	0	0
STAT1 (dimer)	0.016	0.092	-10000	0	-0.29	25	25
JAK2	0.014	0.028	-10000	0	-0.11	23	23
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
EPO/EPOR (dimer)/JAK2	0.044	0.061	-10000	0	-0.12	45	45
EPO/EPOR	0.029	0.013	-10000	0	-10000	0	0
LYN	-0.017	0.097	-10000	0	-0.25	72	72
TEC/VAV2	0.033	0.05	-10000	0	-0.16	8	8
elevation of cytosolic calcium ion concentration	0.02	0.006	-10000	0	-10000	0	0
SHC1	0.004	0.052	-10000	0	-0.14	48	48
EPO/EPOR (dimer)/LYN	0.022	0.067	-10000	0	-0.16	57	57
mol:IP3	0.011	0.09	-10000	0	-0.21	58	58
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.002	0.09	-10000	0	-0.23	50	50
SH2B3	0.013	0.037	-10000	0	-0.15	20	20
NFKB1	0.01	0.057	-10000	0	-0.14	59	59
EPO/EPOR (dimer)/JAK2/SOCS3	0.031	0.052	0.2	43	-10000	0	43
PTPN6	0.018	0.048	-10000	0	-0.12	46	46
TEC/VAV2/GRB2	0.039	0.057	-10000	0	-0.22	10	10
EPOR	0.02	0.006	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	0.018	0.064	-10000	0	-0.2	24	24
SOS1	0	0	-10000	0	-10000	0	0
PLCG2	-0.002	0.069	-10000	0	-0.19	52	52
CRKL/CBL/C3G	0.041	0.05	-10000	0	-0.19	4	4
VAV2	0.021	0.048	-10000	0	-0.17	8	8
CBL	0.021	0.048	-10000	0	-0.17	8	8
SHC/Grb2/SOS1	0.013	0.058	-10000	0	-0.2	21	21
STAT5A	0.015	0.09	-10000	0	-0.28	24	24
GRB2	0.014	0.039	-10000	0	-0.26	10	10
STAT5 (dimer)	0.036	0.089	-10000	0	-0.25	23	23
LYN/PLCgamma2	-0.009	0.095	-10000	0	-0.23	72	72
PTPN11	0.015	0.033	-10000	0	-0.26	7	7
BTK	0.02	0.05	-10000	0	-0.17	9	9
BCL2	0.027	0.092	-10000	0	-0.37	5	5

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.018	0.01	-9999	-0.11	3	3
Rac1/GDP	0.01	0.034	-9999	-0.29	7	7
DOCK1	0.011	0.046	-9999	-0.22	18	18
ITGA4	0.016	0.019	-9999	-0.11	12	12
RAC1	0.015	0.035	-9999	-0.29	7	7
alpha4/beta7 Integrin	0.026	0.016	-9999	-0.14	2	2
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.009	0.053	-9999	-0.28	17	17
alpha4/beta1 Integrin	0.037	0.012	-9999	-10000	0	0
alpha4/beta7 Integrin/Paxillin	0.037	0.015	-9999	-10000	0	0
lamellipodium assembly	-0.027	0.15	-9999	-0.34	86	86
PIK3CA	-0.011	0.085	-9999	-0.22	65	65
PI3K	-0.015	0.092	-9999	-0.21	87	87
ARF6	0.018	0.015	-9999	-0.2	2	2
TLN1	-0.003	0.065	-9999	-0.16	64	64
PXN	0.02	0.007	-9999	-10000	0	0
PIK3R1	-0.015	0.095	-9999	-0.27	62	62
ARF6/GTP	0.044	0.014	-9999	-0.1	1	1
cell adhesion	0.034	0.038	-9999	-0.12	18	18
CRKL/CBL	0.028	0.007	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.038	0.013	-9999	-10000	0	0
ITGB1	0.019	0	-9999	-10000	0	0
ITGB7	0.018	0.01	-9999	-0.11	3	3
ARF6/GDP	0.013	0.014	-9999	-0.2	2	2
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.004	0.073	-9999	-0.12	139	139
p130Cas/Crk/Dock1	0.016	0.044	-9999	-0.18	24	24
VCAM1	-0.078	0.13	-9999	-0.24	201	201
alpha4/beta1 Integrin/Paxillin/Talin	0.036	0.039	-9999	-0.12	18	18
alpha4/beta1 Integrin/Paxillin/GIT1	0.048	0.014	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
mol:GDP	-0.046	0.013	-9999	-10000	0	0
CBL	0.019	0	-9999	-10000	0	0
PRKACA	0.019	0	-9999	-10000	0	0
GIT1	0.019	0.006	-9999	-0.11	1	1
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.036	0.039	-9999	-0.12	18	18
Rac1/GTP	-0.032	0.16	-9999	-0.37	86	86

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	0.024	0.011	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.016	0.019	-9999	-0.11	11	11
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.019	0.006	-9999	-0.11	1	1
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.014	0.034	-9999	-0.18	13	13
RAC1-CDC42/GTP/PAK family	-0.006	0.063	-9999	-0.16	71	71
response to UV	0	0	-9999	-10000	0	0
YES1	0.005	0.061	-9999	-0.24	28	28
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.019	0.006	-9999	-0.11	1	1
FYN	-0.019	0.1	-9999	-0.28	68	68
MAP3K12	0.019	0	-9999	-10000	0	0
FGR	0.005	0.048	-9999	-0.29	7	7
p38 alpha/TAB1	0	0.1	-9999	-0.23	64	64
PRKG1	0.019	0	-9999	-10000	0	0
DUSP8	0.013	0.027	-9999	-0.11	24	24
PGK/cGMP/p38 alpha	-0.003	0.1	-9999	-0.23	63	63
apoptosis	-0.001	0.1	-9999	-0.22	64	64
RAL/GTP	0.014	0.043	-9999	-0.16	27	27
LYN	-0.018	0.097	-9999	-0.25	72	72
DUSP1	-0.005	0.065	-9999	-0.15	74	74
PAK1	0.017	0.017	-9999	-0.11	9	9
SRC	0.019	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.034	0.021	-9999	-0.14	7	7
TRAF6	0.018	0.019	-9999	-0.29	2	2
RAC1	0.015	0.035	-9999	-0.29	7	7
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0.022	0.023	-9999	-0.16	7	7
MAPK11	-0.019	0.13	-9999	-0.29	77	77
BLK	0.018	0.011	-9999	-0.11	4	4
HCK	-0.034	0.11	-9999	-0.21	121	121
MAP2K3	0.018	0.01	-9999	-0.11	3	3
DUSP16	0	0	-9999	-10000	0	0
DUSP10	0.01	0.035	-9999	-0.12	35	35
TRAF6/MEKK3	0.024	0.011	-9999	-0.14	2	2
MAP3K7IP1	0.019	0	-9999	-10000	0	0
MAPK14	-0.009	0.11	-9999	-0.25	65	65
positive regulation of innate immune response	-0.019	0.15	-9999	-0.33	73	73
LCK	0.017	0.016	-9999	-0.11	8	8
p38alpha-beta/MKP7	-0.02	0.14	-9999	-0.32	73	73
p38alpha-beta/MKP5	-0.012	0.14	-9999	-0.32	73	73
PGK/cGMP	0.014	0	-9999	-10000	0	0
PAK2	0.014	0.028	-9999	-0.12	21	21
p38alpha-beta/MKP1	-0.017	0.15	-9999	-0.32	76	76
CDC42	0.017	0.016	-9999	-0.11	8	8
RALB	0.013	0.037	-9999	-0.18	15	15
RALA	0.005	0.063	-9999	-0.26	26	26
PAK3	-0.04	0.11	-9999	-0.19	145	145

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	0.017	0.074	-9999	-0.37	14	14
KLHL20	0.012	0.065	-9999	-0.19	34	34
CYFIP2	-0.019	0.098	-9999	-0.25	74	74
Rac1/GDP	0.028	0.072	-9999	-0.28	23	23
ENAH	0.012	0.087	-9999	-0.38	19	19
AP1M1	0	0	-9999	-10000	0	0
RAP1B	0	0	-9999	0	31	31
RAP1A	0.018	0.019	-9999	-0.29	2	2
CTNNB1	0.017	0.023	-9999	-0.29	3	3
CDC42/GTP	-0.012	0.052	-9999	-0.24	22	22
ABI1/Sra1/Nap1	-0.019	0.043	-9999	-0.14	49	49
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.04	0.033	-9999	-0.15	9	9
RAPGEF1	0.02	0.074	-9999	-0.31	21	21
CTNND1	0.001	0.073	-9999	-0.29	31	31
regulation of calcium-dependent cell-cell adhesion	0.015	0.076	-9999	-0.4	13	13
CRK	0.017	0.08	-9999	-0.33	21	21
E-cadherin/gamma catenin/alpha catenin	0.023	0.046	-9999	-0.13	36	36
alphaE/beta7 Integrin	0.024	0.027	-9999	-0.19	7	7
IQGAP1	-0.008	0.086	-9999	-0.27	49	49
NCKAP1	0.019	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.024	0.01	-9999	-0.14	2	2
DLG1	0.015	0.078	-9999	-0.39	14	14
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.02	0.054	-9999	-0.2	36	36
MLLT4	0.019	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.015	0.036	-9999	-0.14	24	24
PI3K	-0.026	0.071	-9999	-0.26	36	36
ARF6	0.018	0.015	-9999	-0.2	2	2
mol:Ca2+	0	0	-9999	0	97	97
E-cadherin/gamma catenin	0.016	0.039	-9999	-0.14	25	25
TIAM1	0.002	0.066	-9999	-0.23	36	36
E-cadherin(dimer)/Ca2+	0.027	0.06	-9999	-0.18	34	34
AKT1	0.006	0.061	-9999	-0.18	38	38
PIK3R1	-0.015	0.095	-9999	-0.27	62	62
CDH1	0.012	0.029	-9999	-0.11	28	28
RhoA/GDP	0.029	0.069	-9999	-0.26	23	23
actin cytoskeleton organization	0.011	0.049	-9999	-0.12	51	51
CDC42/GDP	0.029	0.067	-9999	-0.26	22	22
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.004	0.068	-9999	-0.24	33	33
ITGB7	0.018	0.01	-9999	-0.11	3	3
RAC1	0.015	0.035	-9999	-0.29	7	7
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.03	0.064	-9999	-0.19	34	34
E-cadherin/Ca2+/beta catenin/alpha catenin	0.025	0.033	-9999	-0.14	15	15
mol:GDP	0.021	0.075	-9999	-0.31	21	21
CDC42/GTP/IQGAP1	0.009	0.052	-9999	-0.16	44	44
JUP	0.007	0.037	-9999	-0.11	47	47
p120 catenin/RhoA/GDP	0.029	0.077	-9999	-0.25	32	32
RAC1/GTP/IQGAP1	0.008	0.055	-9999	-0.16	50	50
PIP5K1C/AP1M1	0.005	0.041	-9999	-0.16	27	27
RHOA	0.015	0.035	-9999	-0.29	7	7
CDC42	0.017	0.016	-9999	-0.11	8	8
CTNNA1	0.011	0.048	-9999	-0.29	13	13
positive regulation of S phase of mitotic cell cycle	0.001	0.054	-9999	-0.14	52	52
NME1	0	0	-9999	0	107	107
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.015	0.081	-9999	-0.38	16	16
regulation of cell-cell adhesion	-0.011	0.045	-9999	-0.21	22	22
WASF2	-0.011	0.023	-9999	-0.074	49	49
Rap1/GTP	0.019	0.067	-9999	-0.26	22	22
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.039	0.049	-9999	-0.14	20	20
CCND1	0	0.066	-9999	-0.18	49	49
VAV2	0.024	0.079	-9999	-0.4	13	13
RAP1/GDP	0.022	0.068	-9999	-0.27	21	21
adherens junction assembly	0.015	0.078	-9999	-0.37	16	16
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.008	0.055	-9999	-0.24	22	22
PIP5K1C	0.006	0.061	-9999	-0.24	27	27
regulation of heterotypic cell-cell adhesion	0.038	0.048	-9999	-0.2	7	7
E-cadherin/beta catenin	0.008	0.033	-9999	-0.15	16	16
mol:GTP	0	0	-9999	0	107	107
SRC	0.017	0.074	-9999	-0.38	13	13
PIK3CA	-0.011	0.085	-9999	-0.22	65	65
Rac1/GTP	-0.031	0.082	-9999	-0.3	34	34
E-cadherin/beta catenin/alpha catenin	0.029	0.039	-9999	-0.17	15	15
ITGAE	0.014	0.037	-9999	-0.29	7	7
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.015	0.078	-9999	-0.4	13	13

×

Regulation of Telomerase

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
Telomerase catalytic core complex	0.001	0.15	-10000	0	-0.52	22	22
RAD9A	0.018	0.013	-10000	0	-0.11	5	5
AP1	-0.03	0.11	-10000	0	-0.24	93	93
IFNAR2	0.018	0.02	-10000	0	-0.29	2	2
AKT1	0.012	0.061	-10000	0	-0.27	22	22
ER alpha/Oestrogen	0.014	0.004	-10000	0	-10000	0	0
NFX1/SIN3/HDAC complex	0.005	0.092	-10000	0	-0.37	21	21
EGF	0.014	0.025	-10000	0	-0.11	21	21
SMG5	0.019	0.008	-10000	0	-0.11	2	2
SMG6	0.016	0.019	-10000	0	-0.11	11	11
SP3/HDAC2	0.014	0.058	-10000	0	-0.21	29	29
TERT/c-Abl	-0.005	0.16	-10000	0	-0.52	27	27
SAP18	0.01	0.052	-10000	0	-0.29	15	15
MRN complex	0.036	0.019	-10000	0	-0.15	4	4
WT1	0.017	0.017	-10000	0	-0.11	8	8
WRN	0.014	0.025	-10000	0	-0.11	20	20
SP1	0.019	0.008	-10000	0	-10000	0	0
SP3	0.012	0.046	-10000	0	-0.29	12	12
TERF2IP	0.006	0.061	-10000	0	-0.28	23	23
Telomerase/Nucleolin	-0.002	0.14	-10000	0	-0.5	24	24
Mad/Max	0.028	0.009	-10000	0	-10000	0	0
TERT	0	0.16	-10000	0	-0.55	20	20
CCND1	-0.044	0.29	-10000	0	-1	39	39
MAX	0.019	0.006	-10000	0	-0.11	1	1
RBBP7	0.015	0.034	-10000	0	-0.25	8	8
RBBP4	-0.005	0.079	-10000	0	-0.24	50	50
TERF2	-0.002	0.068	-10000	0	-0.23	43	43
PTGES3	0.016	0.03	-10000	0	-0.29	5	5
SIN3A	0	0.001	-10000	0	-10000	0	0
Telomerase/911	0.029	0.1	-10000	0	-0.52	11	11
CDKN1B	0	0.1	-10000	0	-0.4	29	29
RAD1	0.014	0.034	-10000	0	-0.18	13	13
XRCC5	0.014	0.038	-10000	0	-0.27	9	9
XRCC6	0.018	0.019	-10000	0	-0.29	2	2
SAP30	0.017	0.027	-10000	0	-0.29	4	4
TRF2/PARP2	0.005	0.072	-10000	0	-0.2	50	50
UBE3A	0.017	0.027	-10000	0	-0.29	4	4
JUN	-0.002	0.077	-10000	0	-0.28	37	37
E6	0	0.003	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.013	0.019	-10000	0	-0.2	4	4
FOS	-0.046	0.12	-10000	0	-0.22	146	146
IFN-gamma/IRF1	0.011	0.072	-10000	0	-0.21	45	45
PARP2	0.006	0.059	-10000	0	-0.25	25	25
BLM	-0.036	0.11	-10000	0	-0.24	110	110
Telomerase	0.014	0.075	-10000	0	-0.44	9	9
IRF1	-0.004	0.07	-10000	0	-0.15	85	85
ESR1	0.019	0.001	-10000	0	-10000	0	0
KU/TER	0.024	0.03	-10000	0	-0.19	10	10
ATM/TRF2	0.015	0.041	-10000	0	-0.097	45	45
ubiquitin-dependent protein catabolic process	0.01	0.092	-10000	0	-0.34	22	22
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.009	0.095	-10000	0	-0.35	22	22
HDAC1	0.013	0.04	-10000	0	-0.22	13	13
HDAC2	0.004	0.062	-10000	0	-0.22	33	33
ATM	0.011	0.05	0.15	39	-0.22	6	45
SMAD3	0.013	0.032	-10000	0	-0.19	8	8
ABL1	-0.012	0.093	-10000	0	-0.28	55	55
MXD1	0.019	0.006	-10000	0	-10000	0	0
MRE11A	0.019	0.006	-10000	0	-0.11	1	1
HUS1	0.019	0.006	-10000	0	-0.11	1	1
RPS6KB1	0.019	0.008	-10000	0	-0.11	2	2
TERT/NF kappa B1/14-3-3	0.016	0.16	-10000	0	-0.52	21	21
NR2F2	-0.029	0.1	-10000	0	-0.22	104	104
MAPK3	0.021	0.007	-10000	0	-10000	0	0
MAPK1	0.014	0.035	-10000	0	-0.19	13	13
TGFB1/TGF beta receptor Type II	0.007	0.049	-10000	0	-0.16	37	37
NFKB1	0.014	0.038	-10000	0	-0.22	12	12
HNRNPC	0.018	0.019	-10000	0	-0.29	2	2
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.011	0.05	0.15	39	-0.22	6	45
NBN	0.017	0.027	-10000	0	-0.29	4	4
EGFR	-0.08	0.12	-10000	0	-0.18	267	267
mol:Oestrogen	0	0.002	-10000	0	-10000	0	0
EGF/EGFR	-0.044	0.082	-10000	0	-0.18	107	107
MYC	-0.022	0.097	-10000	0	-0.21	95	95
IL2	0.019	0.01	-10000	0	-0.11	1	1
KU	0.024	0.03	-10000	0	-0.19	10	10
RAD50	0.018	0.013	-10000	0	-0.11	5	5
HSP90AA1	0.018	0.019	-10000	0	-0.29	2	2
TGFB1	0.007	0.049	-10000	0	-0.16	37	37
TRF2/BLM	-0.022	0.096	-10000	0	-0.2	104	104
FRAP1	0.019	0.006	-10000	0	-0.11	1	1
KU/TERT	0.015	0.15	-10000	0	-0.49	25	25
SP1/HDAC2	0.019	0.046	-10000	0	-0.18	21	21
PINX1	0	0	-10000	0	-10000	0	0
Telomerase/EST1A	0.001	0.14	-10000	0	-0.47	24	24
Smad3/Myc	-0.001	0.062	-10000	0	-0.15	66	66
911 complex	0.035	0.023	-10000	0	-0.15	5	5
IFNG	0.015	0.035	-10000	0	-0.12	30	30
Telomerase/PinX1	-0.032	0.12	-10000	0	-0.47	24	24
Telomerase/AKT1/mTOR/p70S6K	0.029	0.1	-10000	0	-0.56	9	9
SIN3B	0.017	0.025	-10000	0	-0.29	3	3
YWHAE	0.011	0.045	-10000	0	-0.21	19	19
Telomerase/EST1B	0	0.14	-10000	0	-0.47	24	24
response to DNA damage stimulus	0.006	0.017	0.055	39	-0.077	6	45
MRN complex/TRF2/Rap1	0.034	0.067	-10000	0	-0.17	45	45
TRF2/WRN	0.009	0.054	-10000	0	-0.16	43	43
Telomerase/hnRNP C1/C2	0	0.14	-10000	0	-0.48	24	24
E2F1	0.019	0.009	-10000	0	-0.12	1	1
ZNFX1	0	0.001	-10000	0	-10000	0	0
PIF1	0	0	-10000	0	-10000	0	0
NCL	0.01	0.05	-10000	0	-0.27	16	16
DKC1	0.012	0.042	-10000	0	-0.19	18	18
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

p38 MAPK signaling pathway

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
TRAF6/ASK1	0.001	0.061	-9999	-0.16	60	60
TRAF2/ASK1	0.007	0.054	-9999	-0.16	49	49
ATM	0.009	0.042	-9999	-0.15	31	31
MAP2K3	0.001	0.085	-9999	-0.3	26	26
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.002	0.088	-9999	-0.24	54	54
hyperosmotic response	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
GADD45G	0.005	0.041	-9999	-0.11	58	58
TXN	0.002	0.037	-9999	-0.24	12	12
CALM1	0.007	0.056	-9999	-0.21	28	28
GADD45A	-0.022	0.1	-9999	-0.26	78	78
GADD45B	-0.005	0.072	-9999	-0.29	24	24
MAP3K1	0.015	0.022	-9999	-0.11	16	16
MAP3K6	0.016	0.019	-9999	-0.11	11	11
MAP3K7	0.006	0.059	-9999	-0.24	26	26
MAP3K4	-0.002	0.076	-9999	-0.26	39	39
mol:Ca2+	0	0	-9999	-10000	0	0
ASK1/ASK2	0.003	0.065	-9999	-0.19	51	51
TAK1/TAB family	-0.004	0.074	-9999	-0.28	30	30
RAC1/OSM/MEKK3	0.022	0.019	-9999	-0.14	7	7
TRAF2	0.019	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.015	0.064	-9999	-0.26	24	24
TRAF6	0.008	0.047	-9999	-0.23	20	20
RAC1	0.015	0.035	-9999	-0.29	7	7
mol:LPS	0	0	-9999	-10000	0	0
CAMK2B	-0.047	0.11	-9999	-0.29	75	75
CCM2	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.019	0.079	-9999	-0.18	87	87
MAPK11	0.019	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.023	0.092	-9999	-0.16	127	127
OSM/MEKK3	0.014	0.004	-9999	-0.07	1	1
TAOK1	0.003	0.028	-9999	-0.24	6	6
TAOK2	0.012	0.028	-9999	-0.23	6	6
TAOK3	0.005	0.052	-9999	-0.24	20	20
MAP3K7IP1	0.019	0	-9999	-10000	0	0
MAPK14	0.018	0.013	-9999	-0.11	5	5
MAP3K7IP2	0.008	0.057	-9999	-0.27	20	20
MAP3K5	-0.014	0.091	-9999	-0.25	65	65
MAP3K10	0.019	0	-9999	-10000	0	0
MAP3K3	0.019	0.006	-9999	-0.11	1	1
TRX/ASK1	0.009	0.043	-9999	-0.24	12	12
GADD45/MTK1/MTK1	-0.007	0.086	-9999	-0.16	95	95

×

FAS signaling pathway (CD95)

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
SPTAN1	-0.015	0.058	-10000	0	-0.19	48	48
RFC1	-0.009	0.052	-10000	0	-0.2	31	31
PRKDC	-0.011	0.056	-10000	0	-0.21	31	31
RIPK1	0.016	0.019	-10000	0	-0.11	11	11
CASP7	-0.01	0.11	-10000	0	-0.61	16	16
FASLG/FAS/FADD/FAF1	-0.005	0.083	0.16	34	-0.18	70	104
MAP2K4	-0.002	0.098	-10000	0	-0.31	22	22
mol:ceramide	0.005	0.08	-10000	0	-0.24	24	24
GSN	-0.013	0.055	-10000	0	-0.21	30	30
FASLG/FAS/FADD/FAF1/Caspase 8	0.005	0.085	0.16	26	-0.24	22	48
FAS	-0.028	0.099	-10000	0	-0.22	91	91
BID	-0.007	0.04	-10000	0	-0.17	26	26
MAP3K1	-0.004	0.083	-10000	0	-0.36	19	19
MAP3K7	0.006	0.059	-10000	0	-0.24	26	26
RB1	-0.005	0.046	-10000	0	-0.24	18	18
CFLAR	0.016	0.024	-10000	0	-0.2	4	4
HGF/MET	0.012	0.062	-10000	0	-0.16	53	53
ARHGDIB	-0.015	0.061	-10000	0	-0.19	47	47
FADD	0.017	0.021	-10000	0	-0.2	4	4
actin filament polymerization	0.013	0.055	0.21	30	-10000	0	30
NFKB1	-0.001	0.095	-10000	0	-0.78	7	7
MAPK8	0.002	0.094	-10000	0	-0.52	5	5
DFFA	-0.005	0.046	-10000	0	-0.23	20	20
DNA fragmentation during apoptosis	-0.004	0.042	-10000	0	-0.24	15	15
FAS/FADD/MET	0.002	0.066	-10000	0	-0.15	69	69
CFLAR/RIP1	0.024	0.021	-10000	0	-0.19	2	2
FAIM3	0.019	0.008	-10000	0	-0.11	2	2
FAF1	0.006	0.061	-10000	0	-0.28	22	22
PARP1	-0.005	0.048	-10000	0	-0.24	20	20
DFFB	-0.004	0.042	-10000	0	-0.25	15	15
CHUK	0.002	0.089	-10000	0	-0.73	7	7
FASLG	0.019	0.003	-10000	0	-10000	0	0
FAS/FADD	-0.006	0.072	-10000	0	-0.19	57	57
HGF	0.016	0.02	-10000	0	-0.11	13	13
LMNA	-0.002	0.046	-10000	0	-0.21	21	21
CASP6	-0.006	0.048	-10000	0	-0.24	19	19
CASP10	0.019	0.002	-10000	0	-10000	0	0
CASP3	-0.01	0.048	-10000	0	-0.28	15	15
PTPN13	-0.011	0.09	-10000	0	-0.27	54	54
CASP8	-0.006	0.014	-10000	0	-10000	0	0
IL6	-0.004	0.093	-10000	0	-0.64	6	6
MET	0.007	0.037	-10000	0	-0.11	47	47
ICAD/CAD	0	0.043	-10000	0	-0.21	20	20
FASLG/FAS/FADD/FAF1/Caspase 10	0.005	0.08	-10000	0	-0.24	24	24
activation of caspase activity by cytochrome c	-0.007	0.04	-10000	0	-0.17	26	26
PAK2	-0.006	0.044	-10000	0	-0.24	16	16
BCL2	0.019	0	-10000	0	-10000	0	0

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.003	0.1	-10000	0	-0.35	25	25
PDGFB-D/PDGFRB/SLAP	-0.019	0.09	-10000	0	-0.21	82	82
PDGFB-D/PDGFRB/APS/CBL	0.021	0.025	-10000	0	-0.16	8	8
AKT1	0	0.082	-10000	0	-0.22	46	46
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.001	0.098	-10000	0	-0.39	20	20
PIK3CA	-0.011	0.085	-10000	0	-0.22	65	65
FGR	-0.014	0.097	-10000	0	-0.67	8	8
mol:Ca2+	-0.003	0.099	-10000	0	-0.42	20	20
MYC	-0.065	0.25	-10000	0	-0.72	61	61
SHC1	0.004	0.052	-10000	0	-0.14	48	48
HRAS/GDP	0.016	0.059	-10000	0	-0.15	50	50
LRP1/PDGFRB/PDGFB	0.017	0.059	-10000	0	-0.17	37	37
GRB10	-0.018	0.091	-10000	0	-0.2	89	89
PTPN11	0.015	0.033	-10000	0	-0.26	7	7
GO:0007205	-0.004	0.1	-10000	0	-0.42	20	20
PTEN	0.013	0.037	-10000	0	-0.18	16	16
GRB2	0.014	0.039	-10000	0	-0.26	10	10
GRB7	0.016	0.019	-10000	0	-0.11	11	11
PDGFB-D/PDGFRB/SHP2	0.02	0.038	-10000	0	-0.2	14	14
PDGFB-D/PDGFRB/GRB10	-0.004	0.071	-10000	0	-0.2	52	52
cell cycle arrest	-0.019	0.09	-10000	0	-0.21	82	82
HRAS	0.009	0.055	-10000	0	-0.28	18	18
HIF1A	0.001	0.081	-10000	0	-0.22	47	47
GAB1	-0.016	0.12	-10000	0	-0.45	25	25
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	-0.012	0.11	-10000	0	-0.37	30	30
PDGFB-D/PDGFRB	0.027	0.041	-10000	0	-0.17	18	18
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.016	0.047	-10000	0	-0.2	22	22
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.001	0.11	-10000	0	-0.33	31	31
positive regulation of MAPKKK cascade	0.02	0.038	-10000	0	-0.19	14	14
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
mol:IP3	-0.004	0.1	-10000	0	-0.43	20	20
E5	0	0.001	-10000	0	-10000	0	0
CSK	0.013	0.044	-10000	0	-0.29	11	11
PDGFB-D/PDGFRB/GRB7	0.021	0.035	-10000	0	-0.21	9	9
SHB	0.016	0.02	-10000	0	-0.11	13	13
BLK	-0.001	0.044	-10000	0	-0.24	7	7
PTPN2	0.017	0.013	-10000	0	-0.11	5	5
PDGFB-D/PDGFRB/SNX15	0.022	0.03	-10000	0	-0.2	8	8
BCAR1	0	0	-10000	0	-10000	0	0
VAV2	-0.029	0.15	-10000	0	-0.42	46	46
CBL	0.019	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.022	0.03	-10000	0	-0.2	8	8
LCK	-0.003	0.045	-10000	0	-0.26	6	6
PDGFRB	0.01	0.044	-10000	0	-0.18	21	21
ACP1	0.01	0.051	-10000	0	-0.25	18	18
HCK	-0.074	0.19	-10000	0	-0.54	69	69
ABL1	-0.017	0.11	-10000	0	-0.35	35	35
PDGFB-D/PDGFRB/CBL	-0.018	0.13	-10000	0	-0.46	28	28
PTPN1	0.013	0.043	-10000	0	-0.3	10	10
SNX15	0.019	0	-10000	0	-10000	0	0
STAT3	-0.003	0.079	-10000	0	-0.29	37	37
STAT1	0.008	0.04	-10000	0	-0.12	40	40
cell proliferation	-0.055	0.22	-10000	0	-0.64	61	61
SLA	-0.04	0.11	-10000	0	-0.22	127	127
actin cytoskeleton reorganization	0.024	0.049	-10000	0	-0.19	15	15
SRC	-0.002	0.043	-10000	0	-0.23	9	9
PI3K	-0.027	0.061	-10000	0	-0.2	39	39
PDGFB-D/PDGFRB/GRB7/SHC	0.023	0.045	-10000	0	-0.16	21	21
SH2B2	0	0	-10000	0	-10000	0	0
PLCgamma1/SPHK1	0.001	0.1	-10000	0	-0.41	20	20
LYN	-0.057	0.16	-10000	0	-0.48	63	63
LRP1	-0.007	0.079	-10000	0	-0.29	33	33
SOS1	0	0	-10000	0	-10000	0	0
STAT5B	0.018	0.015	-10000	0	-0.2	2	2
STAT5A	0.019	0.008	-10000	0	-0.11	2	2
NCK1-2/p130 Cas	0.03	0.053	-10000	0	-0.15	32	32
SPHK1	0.008	0.037	-10000	0	-0.11	45	45
EDG1	0.001	0.068	-10000	0	-0.22	39	39
mol:DAG	-0.004	0.1	-10000	0	-0.43	20	20
PLCG1	-0.004	0.1	-10000	0	-0.44	20	20
NHERF/PDGFRB	0.028	0.038	-10000	0	-0.16	15	15
YES1	-0.024	0.12	-10000	0	-0.49	28	28
cell migration	0.027	0.038	-10000	0	-0.16	15	15
SHC/Grb2/SOS1	0.027	0.052	-10000	0	-0.15	30	30
SLC9A3R2	0.019	0	-10000	0	-10000	0	0
SLC9A3R1	0.01	0.042	-10000	0	-0.15	29	29
NHERF1-2/PDGFRB/PTEN	0.035	0.043	-10000	0	-0.14	20	20
FYN	-0.067	0.2	-10000	0	-0.56	66	66
DOK1	0.02	0.032	-10000	0	-0.14	18	18
HRAS/GTP	0.007	0.037	-10000	0	-0.2	17	17
PDGFB	0.019	0	-10000	0	-10000	0	0
RAC1	-0.042	0.19	-10000	0	-0.48	69	69
PRKCD	0.017	0.037	-10000	0	-0.15	18	18
FER	0.019	0.034	-10000	0	-0.14	18	18
MAPKKK cascade	-0.008	0.038	0.091	3	-0.16	20	23
RASA1	0.017	0.041	-10000	0	-0.18	18	18
NCK1	0.014	0.036	-10000	0	-0.19	14	14
NCK2	0.009	0.053	-10000	0	-0.28	17	17
p62DOK/Csk	0.029	0.04	-10000	0	-0.13	26	26
PDGFB-D/PDGFRB/SHB	0.02	0.035	-10000	0	-0.2	9	9
chemotaxis	-0.016	0.11	-10000	0	-0.34	35	35
STAT1-3-5/STAT1-3-5	0.024	0.054	-10000	0	-0.17	15	15
Bovine Papilomavirus E5/PDGFRB	0.008	0.03	-10000	0	-0.21	8	8
PTPRJ	0.019	0	-10000	0	-10000	0	0

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.003	0.048	-10000	0	-0.13	57	57
ARNO/beta Arrestin1-2	0.022	0.022	-10000	0	-0.098	8	8
EGFR	-0.08	0.12	-10000	0	-0.18	267	267
EPHA2	0.008	0.036	-10000	0	-0.11	44	44
USP6	0.017	0.017	-10000	0	-10000	0	0
IQSEC1	0.016	0.022	-10000	0	-0.29	1	1
EGFR/EGFR/EGF/EGF	-0.044	0.082	-10000	0	-0.18	107	107
ARRB2	0.013	0.029	-10000	0	-0.23	7	7
mol:GTP	0.006	0.01	0.042	14	-10000	0	14
ARRB1	0.018	0.011	-10000	0	-0.11	4	4
FBXO8	0	0	-10000	0	-10000	0	0
TSHR	0.015	0.022	-10000	0	-0.11	16	16
EGF	0.014	0.025	-10000	0	-0.11	21	21
somatostatin receptor activity	0	0	-10000	0	0	8	8
ARAP2	0	0	-10000	0	0	1	1
mol:GDP	0.016	0.034	-10000	0	-0.14	6	6
mol:PI-3-4-5-P3	0	0	-10000	0	0	6	6
ITGA2B	0.019	0	-10000	0	-10000	0	0
ARF6	0.018	0.015	-10000	0	-0.2	2	2
Ephrin A1/EPHA2/NCK1/GIT1	0.028	0.053	-10000	0	-0.14	36	36
ADAP1	0	0	-10000	0	-10000	0	0
KIF13B	-0.009	0.085	-10000	0	-0.24	57	57
HGF/MET	0.018	0.03	-10000	0	-0.14	4	4
PXN	0.018	0.011	-10000	0	-0.11	4	4
ARF6/GTP	0.022	0.039	-10000	0	-0.16	4	4
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.027	0.072	-10000	0	-0.15	108	108
ADRB2	0.01	0.032	-10000	0	-0.11	35	35
receptor agonist activity	0	0	-10000	0	0	4	4
actin filament binding	0	0	-10000	0	0	7	7
SRC	0.019	0	-10000	0	-10000	0	0
ITGB3	0.019	0.008	-10000	0	-0.11	2	2
GNAQ	0.015	0.023	-10000	0	-0.11	17	17
EFA6/PI-4-5-P2	0	0	-10000	0	-0.001	5	5
ARF6/GDP	0.026	0.03	-10000	0	-0.37	1	1
ARF6/GDP/GULP/ACAP1	0.005	0.055	-10000	0	-0.16	11	11
alphaIIb/beta3 Integrin/paxillin/GIT1	0.048	0.01	-10000	0	-10000	0	0
ACAP1	0	0	-10000	0	-10000	0	0
ACAP2	0	0	-10000	0	0	1	1
LHCGR/beta Arrestin2	0.017	0.022	-10000	0	-0.17	7	7
EFNA1	-0.001	0.07	-10000	0	-0.21	47	47
HGF	0.016	0.02	-10000	0	-0.11	13	13
CYTH3	0	0	-10000	0	0	4	4
CYTH2	0	0.001	-10000	0	-0.003	7	7
NCK1	0.014	0.036	-10000	0	-0.19	14	14
fibronectin binding	0	0	-10000	0	0	5	5
endosomal lumen acidification	0	0	-10000	0	0	16	16
microtubule-based process	0	0	-10000	0	-10000	0	0
GULP1	-0.047	0.11	-10000	0	-0.18	174	174
GNAQ/ARNO	0.012	0.01	-10000	0	-0.042	17	17
mol:Phosphatidic acid	0	0	-10000	0	0	1	1
PIP3-E	0.002	0.049	-10000	0	-0.12	64	64
MET	0.007	0.037	-10000	0	-0.11	47	47
GNA14	0.015	0.022	-10000	0	-0.11	15	15
GNA15	0.012	0.033	-10000	0	-0.12	26	26
GIT1	0.019	0.006	-10000	0	-0.11	1	1
mol:PI-4-5-P2	0	0	-10000	0	0	4	4
GNA11	0.003	0.068	-10000	0	-0.29	27	27
LHCGR	0.019	0	-10000	0	-10000	0	0
AGTR1	0.016	0.02	-10000	0	-0.11	13	13
desensitization of G-protein coupled receptor protein signaling pathway	0.017	0.022	-10000	0	-0.17	7	7
IPCEF1/ARNO	-0.022	0.058	-10000	0	-0.11	123	123
alphaIIb/beta3 Integrin	0.028	0.006	-10000	0	-10000	0	0

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.027	0.045	0.19	10	-0.23	6	16
AES	0.024	0.046	0.17	12	-0.21	9	21
FBXW11	0.011	0.047	-10000	0	-0.26	14	14
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.021	0.026	-10000	0	-0.16	2	2
SMAD4	-0.004	0.079	-10000	0	-0.29	36	36
DKK2	0.013	0.028	-10000	0	-0.11	25	25
TLE1	0.027	0.034	0.16	11	-0.15	5	16
MACF1	-0.004	0.081	-10000	0	-0.28	41	41
CTNNB1	0.029	0.085	0.2	2	-0.35	17	19
WIF1	-0.006	0.051	-10000	0	-0.11	100	100
beta catenin/RanBP3	0.062	0.15	0.39	72	-0.32	6	78
KREMEN2	0.019	0.006	-10000	0	-0.11	1	1
DKK1	-0.018	0.059	-10000	0	-0.11	149	149
beta catenin/beta TrCP1	0.037	0.089	0.2	2	-0.36	18	20
FZD1	0.015	0.023	-10000	0	-0.11	17	17
AXIN2	-0.039	0.093	0.12	2	-0.25	71	73
AXIN1	0.019	0.001	-10000	0	-10000	0	0
RAN	0.016	0.031	-10000	0	-0.24	7	7
Axin1/APC/GSK3/beta catenin	0.009	0.16	-10000	0	-0.64	26	26
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.028	0.13	0.25	5	-0.46	23	28
Axin1/APC/GSK3	0.02	0.096	0.19	1	-0.37	23	24
Axin1/APC/GSK3/beta catenin/Macf1	0.013	0.12	-10000	0	-0.39	35	35
HNF1A	0.03	0.03	0.16	12	-10000	0	12
CTBP1	0.023	0.048	0.16	9	-0.29	8	17
MYC	-0.14	0.4	-10000	0	-1.3	53	53
RANBP3	0.019	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.031	0.026	-10000	0	-0.13	2	2
NKD1	0	0	-10000	0	-10000	0	0
TCF4	0.011	0.075	0.18	7	-0.26	30	37
TCF3	0.03	0.03	0.16	12	-10000	0	12
WNT1/LRP6/FZD1/Axin1	0.043	0.024	-10000	0	-0.11	2	2
Ran/GTP	0.013	0.021	-10000	0	-0.19	5	5
CtBP/CBP/TCF/TLE1/AES	0.079	0.18	0.48	69	-0.39	6	75
LEF1	0.029	0.035	0.18	12	-0.11	5	17
DVL1	0.018	0.11	-10000	0	-0.41	22	22
CSNK2A1	0.01	0.053	-10000	0	-0.29	16	16
beta catenin/TCF/CtBP/CBP/TLE1/AES	-0.004	0.18	-10000	0	-0.51	39	39
DKK1/LRP6/Kremen 2	0.012	0.041	-10000	0	-0.12	6	6
LRP6	0.013	0.029	-10000	0	-0.12	23	23
CSNK1A1	0.028	0.044	0.19	11	-0.29	4	15
NLK	0.002	0.059	-10000	0	-0.18	41	41
CCND1	-0.12	0.35	-10000	0	-1.3	38	38
WNT1	0.019	0.006	-10000	0	-0.11	1	1
GSK3A	0.019	0.001	-10000	0	-10000	0	0
GSK3B	0.004	0.066	-10000	0	-0.26	29	29
FRAT1	0.016	0.023	-10000	0	-0.13	12	12
PPP2R5D	0.021	0.044	-10000	0	-0.22	12	12
APC	0.024	0.027	-10000	0	-0.18	5	5
WNT1/LRP6/FZD1	0.024	0.05	-10000	0	-0.23	11	11
CREBBP	0.03	0.03	0.16	12	-10000	0	12

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.21	0.53	-9999	-1.1	134	134
IL23A	-0.025	0.28	-9999	-1	18	18
NF kappa B1 p50/RelA/I kappa B alpha	-0.01	0.27	-9999	-0.75	32	32
positive regulation of T cell mediated cytotoxicity	-0.024	0.28	-9999	-0.82	32	32
ITGA3	-0.022	0.27	-9999	-0.88	20	20
IL17F	-0.026	0.22	-9999	-0.56	37	37
IL12B	0.022	0.03	-9999	-10000	0	0
STAT1 (dimer)	-0.025	0.27	-9999	-0.79	32	32
CD4	-0.044	0.34	-9999	-1.1	35	35
IL23	-0.024	0.28	-9999	-0.99	18	18
IL23R	0.006	0.069	-9999	-0.15	19	19
IL1B	-0.038	0.32	-9999	-1.2	23	23
T-helper cell lineage commitment	0	0	-9999	-10000	0	0
IL24	-0.014	0.26	-9999	-0.83	19	19
TYK2	0.012	0.052	-9999	-0.29	12	12
STAT4	0.012	0.03	-9999	-0.11	30	30
STAT3	-0.003	0.079	-9999	-0.29	37	37
IL18RAP	0.018	0.015	-9999	-0.11	7	7
IL12RB1	0.019	0.024	-9999	-0.15	1	1
PIK3CA	-0.01	0.085	-9999	-0.22	65	65
IL12Rbeta1/TYK2	0.018	0.049	-9999	-0.18	21	21
IL23R/JAK2	0.018	0.093	-9999	-0.18	17	17
positive regulation of chronic inflammatory response	-0.024	0.28	-9999	-0.82	32	32
natural killer cell activation	0	0.006	-9999	-10000	0	0
JAK2	0.016	0.042	-9999	-0.13	16	16
PIK3R1	-0.014	0.095	-9999	-0.27	62	62
NFKB1	0.014	0.038	-9999	-0.22	12	12
RELA	0.018	0.02	-9999	-0.23	3	3
positive regulation of dendritic cell antigen processing and presentation	-0.021	0.27	-9999	-0.94	18	18
ALOX12B	-0.014	0.26	-9999	-0.83	19	19
CXCL1	-0.02	0.26	-9999	-0.85	18	18
T cell proliferation	-0.024	0.28	-9999	-0.82	32	32
NFKBIA	0.003	0.067	-9999	-0.24	34	34
IL17A	-0.001	0.19	-9999	-0.44	37	37
PI3K	-0.038	0.28	-9999	-0.78	37	37
IFNG	0.012	0.016	-9999	-10000	0	0
STAT3 (dimer)	-0.037	0.28	-9999	-0.78	37	37
IL18R1	0.019	0.011	-9999	-0.11	4	4
IL23/IL23R/JAK2/TYK2/SOCS3	0.005	0.18	-9999	-0.48	23	23
IL18/IL18R	0.03	0.039	-9999	-0.14	13	13
macrophage activation	-0.002	0.016	-9999	-0.043	16	16
TNF	-0.02	0.27	-9999	-0.91	19	19
STAT3/STAT4	-0.023	0.27	-9999	-0.77	34	34
STAT4 (dimer)	-0.023	0.27	-9999	-0.79	32	32
IL18	0	0.056	-9999	-0.13	70	70
IL19	-0.014	0.26	-9999	-0.84	18	18
STAT5A (dimer)	-0.021	0.27	-9999	-0.79	32	32
STAT1	0.008	0.04	-9999	-0.12	40	40
SOCS3	0.019	0	-9999	-10000	0	0
CXCL9	-0.023	0.26	-9999	-0.81	21	21
MPO	-0.013	0.26	-9999	-0.81	21	21
positive regulation of humoral immune response	-0.024	0.28	-9999	-0.82	32	32
IL23/IL23R/JAK2/TYK2	-0.025	0.29	-9999	-0.84	32	32
IL6	-0.025	0.26	-9999	-0.88	18	18
STAT5A	0.019	0.008	-9999	-0.11	2	2
IL2	0.021	0.007	-9999	-0.1	1	1
positive regulation of tyrosine phosphorylation of STAT protein	0	0.006	-9999	-10000	0	0
CD3E	-0.014	0.26	-9999	-0.83	19	19
keratinocyte proliferation	-0.024	0.28	-9999	-0.82	32	32
NOS2	-0.021	0.26	-9999	-0.74	32	32

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.019	0.044	-10000	0	-0.19	22	22
ATM	0.009	0.042	-10000	0	-0.15	31	31
UBE2D3	0.017	0.023	-10000	0	-0.29	3	3
PRKDC	0.002	0.063	-10000	0	-0.2	40	40
ATR	0.011	0.049	-10000	0	-0.26	16	16
UBE2L3	0.014	0.038	-10000	0	-0.29	8	8
FANCD2	0.005	0.053	-10000	0	-0.26	17	17
protein ubiquitination	0.029	0.052	-10000	0	-0.13	34	34
XRCC5	0.014	0.038	-10000	0	-0.27	9	9
XRCC6	0.018	0.019	-10000	0	-0.29	2	2
M/R/N Complex	0.036	0.019	-10000	0	-0.15	4	4
MRE11A	0.019	0.006	-10000	0	-0.11	1	1
DNA-PK	0.025	0.052	-10000	0	-0.19	25	25
FA complex/FANCD2/Ubiquitin	0.017	0.072	-10000	0	-0.29	22	22
FANCF	0.011	0.048	-10000	0	-0.24	17	17
BRCA1	0.017	0.015	-10000	0	-0.11	7	7
CCNE1	0.01	0.033	-10000	0	-0.11	37	37
CDK2/Cyclin E1	0.017	0.036	-10000	0	-0.14	14	14
FANCG	0	0.064	-10000	0	-0.18	50	50
BRCA1/BACH1/BARD1	0.018	0.045	-10000	0	-0.19	23	23
FANCE	0.018	0.011	-10000	0	-0.11	4	4
FANCC	0.019	0.008	-10000	0	-0.11	2	2
NBN	0.017	0.027	-10000	0	-0.29	4	4
FANCA	0.019	0.006	-10000	0	-0.11	1	1
DNA repair	0.021	0.077	-10000	0	-0.23	30	30
BRCA1/BARD1/ubiquitin	0.018	0.045	-10000	0	-0.19	23	23
BARD1/DNA-PK	0.029	0.064	-10000	0	-0.17	40	40
FANCL	0	0	-10000	0	-10000	0	0
mRNA polyadenylation	-0.019	0.044	0.19	22	-10000	0	22
BRCA1/BARD1/CTIP/M/R/N Complex	0.014	0.067	-10000	0	-0.23	28	28
BRCA1/BACH1/BARD1/TopBP1	0.017	0.064	-10000	0	-0.16	54	54
BRCA1/BARD1/P53	0.021	0.067	-10000	0	-0.15	61	61
BARD1/CSTF1/BRCA1	0.029	0.039	-10000	0	-0.15	23	23
BRCA1/BACH1	0.017	0.015	-10000	0	-0.11	7	7
BARD1	0.006	0.062	-10000	0	-0.28	24	24
PCNA	0.004	0.065	-10000	0	-0.25	30	30
BRCA1/BARD1/UbcH5C	0.029	0.044	-10000	0	-0.16	24	24
BRCA1/BARD1/UbcH7	0.027	0.047	-10000	0	-0.16	29	29
BRCA1/BARD1/RAD51/PCNA	0.032	0.057	-10000	0	-0.15	41	41
BARD1/DNA-PK/P53	0.023	0.076	-10000	0	-0.15	67	67
BRCA1/BARD1/Ubiquitin	0.018	0.045	-10000	0	-0.19	23	23
BRCA1/BARD1/CTIP	0.015	0.064	-10000	0	-0.16	52	52
FA complex	0.016	0.059	-10000	0	-0.18	37	37
BARD1/EWS	0.019	0.044	-10000	0	-0.19	22	22
RBBP8	0.001	0.055	-10000	0	-0.19	34	34
TP53	-0.007	0.077	-10000	0	-0.2	62	62
TOPBP1	-0.003	0.078	-10000	0	-0.27	40	40
G1/S transition of mitotic cell cycle	-0.02	0.066	0.15	61	-10000	0	61
BRCA1/BARD1	0.033	0.054	-10000	0	-0.13	34	34
CSTF1	0.019	0.006	-10000	0	-0.11	1	1
BARD1/EWS-Fli1	0.005	0.042	-10000	0	-0.2	22	22
CDK2	0.011	0.034	-10000	0	-0.12	29	29
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.018	0.01	-10000	0	-0.11	3	3
RAD50	0.018	0.013	-10000	0	-0.11	5	5
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.018	0.045	-10000	0	-0.19	23	23
EWSR1	0.019	0	-10000	0	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.013	0.04	-9999	-0.22	13	13
HDAC2	0.004	0.061	-9999	-0.22	33	33
GNB1/GNG2	0.019	0.036	-9999	-0.16	21	21
forebrain development	0.021	0.067	-9999	-0.37	6	6
GNAO1	-0.013	0.085	-9999	-0.2	81	81
SMO/beta Arrestin2	0.026	0.029	-9999	-0.19	7	7
SMO	0.019	0.011	-9999	-0.11	4	4
ARRB2	0.014	0.039	-9999	-0.2	15	15
GLI3/SPOP	-0.003	0.11	-9999	-0.29	58	58
mol:GTP	0.001	0.001	-9999	-10000	0	0
GSK3B	0.004	0.066	-9999	-0.26	29	29
GNAI2	0.001	0.073	-9999	-0.28	34	34
SIN3/HDAC complex	0.029	0.038	-9999	-0.16	19	19
GNAI1	-0.046	0.11	-9999	-0.2	158	158
XPO1	0.02	0.024	-9999	-0.29	3	3
GLI1/Su(fu)	0.022	0.063	-9999	-0.32	9	9
SAP30	0.016	0.027	-9999	-0.29	4	4
mol:GDP	0.019	0.011	-9999	-0.11	4	4
MIM/GLI2A	0.026	0.005	-9999	-10000	0	0
IFT88	0.017	0.022	-9999	-0.17	6	6
GNAI3	0.015	0.038	-9999	-0.29	8	8
GLI2	0.018	0.093	-9999	-0.38	21	21
GLI3	-0.01	0.11	-9999	-0.28	56	56
CSNK1D	0.01	0.052	-9999	-0.27	17	17
CSNK1E	0.003	0.064	-9999	-0.23	34	34
SAP18	0.01	0.051	-9999	-0.29	15	15
embryonic digit morphogenesis	0.017	0.022	-9999	-0.17	6	6
GNG2	0	0	-9999	-10000	0	0
Gi family/GTP	-0.036	0.12	-9999	-0.28	72	72
SIN3B	0.016	0.025	-9999	-0.29	3	3
SIN3A	0	0	-9999	-10000	0	0
GLI3/Su(fu)	0	0.091	-9999	-0.27	41	41
GLI2/Su(fu)	0.021	0.084	-9999	-0.33	22	22
FOXA2	0.033	0.027	-9999	-10000	0	0
neural tube patterning	0.021	0.067	-9999	-0.37	6	6
SPOP	0.008	0.058	-9999	-0.29	19	19
Su(fu)/PIAS1	0.015	0.033	-9999	-0.13	23	23
GNB1	0.007	0.061	-9999	-0.29	21	21
CSNK1G2	0.018	0.013	-9999	-0.29	1	1
CSNK1G3	0.017	0.025	-9999	-0.29	3	3
MTSS1	0.026	0.005	-9999	-10000	0	0
embryonic limb morphogenesis	0.021	0.067	-9999	-0.37	6	6
SUFU	0.009	0.017	-9999	-0.13	7	7
LGALS3	-0.039	0.12	-9999	-0.27	107	107
catabolic process	0.011	0.14	-9999	-0.44	39	39
GLI3A/CBP	0.027	0.016	-9999	-10000	0	0
KIF3A	-0.007	0.083	-9999	-0.26	49	49
GLI1	0.021	0.068	-9999	-0.38	6	6
RAB23	0.01	0.041	-9999	-0.14	31	31
CSNK1A1	0.014	0.038	-9999	-0.29	8	8
IFT172	0	0	-9999	-10000	0	0
RBBP7	0.015	0.034	-9999	-0.25	8	8
Su(fu)/Galectin3	-0.009	0.062	-9999	-0.14	99	99
GNAZ	-0.007	0.082	-9999	-0.24	55	55
RBBP4	-0.005	0.079	-9999	-0.24	50	50
CSNK1G1	0.019	0	-9999	-10000	0	0
PIAS1	0.008	0.056	-9999	-0.29	18	18
PRKACA	0.019	0	-9999	-10000	0	0
GLI2/SPOP	0.023	0.098	-9999	-0.37	25	25
STK36	0.003	0.002	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.042	0.14	-9999	-0.37	58	58
PTCH1	0.026	0.065	-9999	-0.53	2	2
MIM/GLI1	0.04	0.07	-9999	-0.39	5	5
CREBBP	0.027	0.016	-9999	-10000	0	0
Su(fu)/SIN3/HDAC complex	0.006	0.098	-9999	-0.25	51	51

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	0.01	0.017	-9999	-0.05	37	37
SNTA1	0.007	0.043	-9999	-0.13	45	45
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.014	0.021	-9999	-0.045	59	59
MAPK12	0.016	0.028	-9999	-0.16	11	11
CCND1	-0.016	0.1	-9999	-0.37	40	40
p38 gamma/SNTA1	0.022	0.031	-9999	-0.15	11	11
MAP2K3	0.018	0.01	-9999	-0.11	3	3
PKN1	0.008	0.049	-9999	-0.18	28	28
G2/M transition checkpoint	0.016	0.028	-9999	-0.16	11	11
MAP2K6	0.014	0.031	-9999	-0.19	11	11
MAPT	-0.019	0.097	-9999	-0.24	79	79
MAPK13	0.015	0.021	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.01	0.036	-9999	-0.23	11	11

×

ErbB4 signaling events

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
ErbB4/ErbB4/HBEGF/HBEGF	0.008	0.13	-10000	0	-0.63	19	19
epithelial cell differentiation	0.013	0.12	-10000	0	-0.63	18	18
ITCH	0.015	0.024	-10000	0	-0.11	5	5
WWP1	-0.015	0.23	-10000	0	-1.2	18	18
FYN	-0.019	0.1	-10000	0	-0.28	68	68
EGFR	-0.08	0.12	-10000	0	-0.18	267	267
PRL	0.016	0.019	-10000	0	-0.11	12	12
neuron projection morphogenesis	0.02	0.11	-10000	0	-0.46	21	21
PTPRZ1	-0.01	0.09	-10000	0	-0.29	49	49
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.031	0.11	-10000	0	-0.5	20	20
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	0.01	0.11	-10000	0	-0.56	19	19
ADAM17	0.014	0.025	-10000	0	-0.11	7	7
ErbB4/ErbB4	0.004	0.14	-10000	0	-0.69	19	19
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.003	0.12	-10000	0	-0.63	19	19
NCOR1	0.009	0.054	-10000	0	-0.27	18	18
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	0.01	0.12	-10000	0	-0.58	20	20
GRIN2B	0.01	0.12	-10000	0	-0.55	20	20
ErbB4/ErbB2/betacellulin	0.02	0.11	-10000	0	-0.55	18	18
STAT1	0.008	0.04	-10000	0	-0.12	40	40
HBEGF	0.015	0.022	-10000	0	-0.11	15	15
PRLR	0.019	0	-10000	0	-10000	0	0
E4ICDs/ETO2	0.009	0.13	-10000	0	-0.63	19	19
axon guidance	-0.001	0.16	-10000	0	-0.8	18	18
NEDD4	0.01	0.034	-10000	0	-0.13	6	6
Prolactin receptor/Prolactin receptor/Prolactin	0.026	0.014	-10000	0	-10000	0	0
CBFA2T3	0.016	0.019	-10000	0	-0.11	11	11
ErbB4/ErbB2/HBEGF	0.018	0.11	-10000	0	-0.53	19	19
MAPK3	0.021	0.1	-10000	0	-0.47	20	20
STAT1 (dimer)	0.006	0.13	-10000	0	-0.62	19	19
MAPK1	0.019	0.11	-10000	0	-0.47	22	22
JAK2	0.013	0.027	-10000	0	-0.11	23	23
ErbB4/ErbB2/neuregulin 1 beta	0.015	0.11	-10000	0	-0.55	18	18
NRG1	0.018	0.016	-10000	0	-10000	0	0
NRG3	0	0	-10000	0	-10000	0	0
NRG2	0.019	0.006	-10000	0	-0.11	1	1
NRG4	0	0	-10000	0	-10000	0	0
heart development	-0.001	0.16	-10000	0	-0.8	18	18
neural crest cell migration	0.015	0.11	-10000	0	-0.54	18	18
ERBB2	0.018	0.016	-10000	0	-10000	0	0
WWOX/E4ICDs	0.01	0.13	-10000	0	-0.63	19	19
SHC1	0.004	0.052	-10000	0	-0.14	48	48
ErbB4/EGFR/neuregulin 4	-0.038	0.13	-10000	0	-0.59	21	21
apoptosis	-0.004	0.12	0.58	19	-10000	0	19
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	0.01	0.13	-10000	0	-0.63	19	19
ErbB4/ErbB2/epiregulin	0.018	0.11	-10000	0	-0.55	18	18
ErbB4/ErbB4/betacellulin/betacellulin	0.01	0.13	-10000	0	-0.63	19	19
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.034	0.12	-10000	0	-0.54	19	19
MDM2	0.003	0.13	-10000	0	-0.63	19	19
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	0.016	0.1	-10000	0	-0.51	18	18
STAT5A	0.002	0.15	-10000	0	-0.76	18	18
ErbB4/EGFR/neuregulin 1 beta	-0.01	0.12	-10000	0	-0.59	18	18
DLG4	0.019	0	-10000	0	-10000	0	0
GRB2/SHC	0.014	0.046	-10000	0	-0.2	16	16
E4ICDs/TAB2/NCoR1	0.011	0.13	-10000	0	-0.66	18	18
STAT5A (dimer)	0.023	0.14	-10000	0	-0.7	18	18
MAP3K7IP2	0.008	0.057	-10000	0	-0.27	20	20
STAT5B (dimer)	0.008	0.15	-10000	0	-0.76	18	18
LRIG1	-0.02	0.098	-10000	0	-0.24	80	80
EREG	0.015	0.023	-10000	0	-0.11	17	17
BTC	0.019	0.006	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.001	0.16	-10000	0	-0.81	18	18
ERBB4	0.004	0.14	-10000	0	-0.7	19	19
STAT5B	0.018	0.015	-10000	0	-0.2	2	2
YAP1	-0.084	0.21	-10000	0	-0.51	96	96
GRB2	0.014	0.039	-10000	0	-0.26	10	10
ErbB4/ErbB2/neuregulin 4	0.007	0.11	-10000	0	-0.55	18	18
glial cell differentiation	-0.011	0.13	0.65	18	-10000	0	18
WWOX	0.019	0.008	-10000	0	-0.11	2	2
cell proliferation	0.019	0.11	-10000	0	-0.57	18	18

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	0.018	0.015	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.032	0.032	-10000	0	-0.14	13	13
CDKN1B	-0.002	0.12	-10000	0	-0.39	39	39
CDKN1A	-0.008	0.12	-10000	0	-0.4	39	39
FRAP1	0.019	0.006	-10000	0	-0.11	1	1
PRKDC	0.002	0.063	-10000	0	-0.2	40	40
FOXO3	-0.004	0.13	-10000	0	-0.42	39	39
AKT1	-0.003	0.12	-10000	0	-0.39	39	39
BAD	0.014	0.036	-10000	0	-0.25	9	9
AKT3	0.017	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.001	0.11	-10000	0	-0.37	39	39
AKT1/ASK1	-0.007	0.12	-10000	0	-0.41	39	39
BAD/YWHAZ	0.033	0.033	-10000	0	-0.16	13	13
RICTOR	0	0	-10000	0	-10000	0	0
RAF1	0.008	0.057	-10000	0	-0.28	19	19
JNK cascade	0.007	0.12	0.4	39	-10000	0	39
TSC1	-0.002	0.12	-10000	0	-0.41	39	39
YWHAZ	0.014	0.037	-10000	0	-0.29	7	7
AKT1/RAF1	0.004	0.13	-10000	0	-0.42	39	39
EP300	0.012	0.046	-10000	0	-0.24	15	15
mol:GDP	-0.003	0.11	-10000	0	-0.38	39	39
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	-0.002	0.12	-10000	0	-0.4	39	39
YWHAQ	0.018	0.019	-10000	0	-0.29	2	2
TBC1D4	0.018	0.01	-10000	0	-10000	0	0
MAP3K5	-0.014	0.091	-10000	0	-0.25	65	65
MAPKAP1	0.013	0.038	-10000	0	-0.21	13	13
negative regulation of cell cycle	0.001	0.12	0.38	28	-10000	0	28
YWHAH	-0.006	0.082	-10000	0	-0.25	49	49
AKT1S1	-0.003	0.11	-10000	0	-0.37	39	39
CASP9	-0.001	0.11	-10000	0	-0.37	39	39
YWHAB	0.015	0.035	-10000	0	-0.29	7	7
p27Kip1/KPNA1	0.003	0.12	-10000	0	-0.38	41	41
GBL	0.016	0.029	-10000	0	-0.2	8	8
PDK1/Src/Hsp90	0.038	0.012	-10000	0	-0.15	2	2
YWHAE	0.011	0.045	-10000	0	-0.21	19	19
SRC	0.019	0	-10000	0	-10000	0	0
AKT2/p21CIP1	-0.008	0.11	-10000	0	-0.34	39	39
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.02	0.055	-10000	0	-0.48	4	4
CHUK	0	0.11	-10000	0	-0.37	39	39
BAD/BCL-XL	0.018	0.11	-10000	0	-0.35	39	39
mTORC2	0.032	0.028	-10000	0	-0.15	10	10
AKT2	0.017	0	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	-0.002	0.15	-10000	0	-0.41	45	45
PDPK1	0.019	0	-10000	0	-10000	0	0
MDM2	-0.002	0.11	-10000	0	-0.37	39	39
MAPKKK cascade	-0.004	0.12	0.41	39	-10000	0	39
MDM2/Cbp/p300	0.017	0.11	-10000	0	-0.36	39	39
TSC1/TSC2	-0.002	0.13	-10000	0	-0.42	39	39
proteasomal ubiquitin-dependent protein catabolic process	0.016	0.11	-10000	0	-0.34	39	39
glucose import	0.02	0.011	-10000	0	-0.13	1	1
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.015	0.073	-10000	0	-0.22	42	42
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	0.02	0.009	-10000	0	-10000	0	0
GSK3A	0.001	0.11	-10000	0	-0.37	39	39
FOXO1	-0.007	0.13	-10000	0	-0.42	39	39
GSK3B	-0.004	0.13	-10000	0	-0.43	39	39
SFN	0.002	0.044	-10000	0	-0.11	70	70
G1/S transition of mitotic cell cycle	-0.001	0.12	-10000	0	-0.41	39	39
p27Kip1/14-3-3 family	0.008	0.13	-10000	0	-0.43	24	24
PRKACA	0.019	0	-10000	0	-10000	0	0
KPNA1	0.013	0.042	-10000	0	-0.29	10	10
HSP90AA1	0.018	0.019	-10000	0	-0.29	2	2
YWHAG	0	0	-10000	0	-10000	0	0
RHEB	0.019	0	-10000	0	-10000	0	0
CREBBP	0.019	0	-10000	0	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	0.012	0.093	-10000	0	-0.37	24	24
CRKL	0.009	0.097	-10000	0	-0.4	24	24
HRAS	0.024	0.095	-10000	0	-0.32	28	28
mol:PIP3	-0.005	0.096	0.28	3	-0.38	24	27
SPRED1	0	0	-10000	0	-10000	0	0
SPRED2	0.019	0.006	-10000	0	-0.11	1	1
GAB1	0.006	0.1	-10000	0	-0.42	24	24
FOXO3	-0.015	0.14	0.21	2	-0.42	47	49
AKT1	-0.014	0.13	-10000	0	-0.41	46	46
BAD	-0.01	0.12	0.21	2	-0.38	46	48
megakaryocyte differentiation	0	0.1	-10000	0	-0.43	24	24
GSK3B	-0.014	0.13	0.21	2	-0.41	48	50
RAF1	0.023	0.084	-10000	0	-0.28	30	30
SHC1	0.004	0.052	-10000	0	-0.14	48	48
STAT3	0.005	0.1	-10000	0	-0.42	24	24
STAT1	0.005	0.21	-10000	0	-0.92	24	24
HRAS/SPRED1	0.018	0.081	-10000	0	-0.27	28	28
cell proliferation	0.011	0.098	-10000	0	-0.4	24	24
PIK3CA	-0.011	0.085	-10000	0	-0.22	65	65
TEC	0.019	0	-10000	0	-10000	0	0
RPS6KB1	0.006	0.1	-10000	0	-0.41	24	24
HRAS/SPRED2	0.029	0.084	-10000	0	-0.27	27	27
LYN/TEC/p62DOK	0.016	0.1	-10000	0	-0.4	24	24
MAPK3	0.023	0.071	-10000	0	-0.21	32	32
STAP1	0.01	0.1	-10000	0	-0.41	24	24
GRAP2	0.019	0	-10000	0	-10000	0	0
JAK2	0.009	0.18	-10000	0	-0.78	24	24
STAT1 (dimer)	0.006	0.2	-10000	0	-0.9	24	24
mol:Gleevec	-0.001	0.004	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	0.029	0.098	-10000	0	-0.38	24	24
actin filament polymerization	0.006	0.097	-10000	0	-0.41	24	24
LYN	-0.018	0.097	-10000	0	-0.25	72	72
STAP1/STAT5A (dimer)	0.017	0.13	-10000	0	-0.56	24	24
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
CBL/CRKL/GRB2	0.024	0.094	-10000	0	-0.36	24	24
PI3K	-0.003	0.12	-10000	0	-0.36	36	36
PTEN	0.013	0.037	-10000	0	-0.18	16	16
SCF/KIT/EPO/EPOR	0.007	0.25	-10000	0	-1.1	24	24
MAPK8	0.011	0.099	-10000	0	-0.41	24	24
STAT3 (dimer)	0.006	0.099	-10000	0	-0.41	24	24
positive regulation of transcription	0.023	0.06	-10000	0	-0.17	32	32
mol:GDP	0.026	0.091	-10000	0	-0.34	24	24
PIK3C2B	0.005	0.1	-10000	0	-0.42	24	24
CBL/CRKL	0.018	0.095	-10000	0	-0.37	24	24
FER	0.01	0.1	-10000	0	-0.41	24	24
SH2B3	0.003	0.1	-10000	0	-0.43	24	24
PDPK1	-0.002	0.091	0.27	3	-0.35	24	27
SNAI2	-0.004	0.11	-10000	0	-0.45	24	24
positive regulation of cell proliferation	0.009	0.16	-10000	0	-0.69	24	24
KITLG	0.021	0.01	-10000	0	-10000	0	0
cell motility	0.009	0.16	-10000	0	-0.69	24	24
PTPN6	0.005	0.056	-10000	0	-0.2	33	33
EPOR	0.034	0.065	-10000	0	-10000	0	0
STAT5A (dimer)	0.016	0.13	-10000	0	-0.57	24	24
SOCS1	0.019	0	-10000	0	-10000	0	0
cell migration	-0.011	0.098	0.4	24	-10000	0	24
SOS1	0	0	-10000	0	-10000	0	0
EPO	0.02	0.006	-10000	0	-10000	0	0
VAV1	0.016	0.019	-10000	0	-0.11	12	12
GRB10	0.001	0.1	-10000	0	-0.43	24	24
PTPN11	0.014	0.033	-10000	0	-0.26	7	7
SCF/KIT	0.006	0.1	-10000	0	-0.43	24	24
GO:0007205	-0.001	0.005	-10000	0	-10000	0	0
MAP2K1	0.022	0.074	-10000	0	-0.22	32	32
CBL	0.019	0	-10000	0	-10000	0	0
KIT	-0.019	0.26	-10000	0	-1.2	24	24
MAP2K2	0.023	0.072	-10000	0	-0.22	31	31
SHC/Grb2/SOS1	0.011	0.097	-10000	0	-0.39	24	24
STAT5A	0.015	0.14	-10000	0	-0.58	24	24
GRB2	0.014	0.039	-10000	0	-0.26	10	10
response to radiation	-0.004	0.11	-10000	0	-0.44	24	24
SHC/GRAP2	0.018	0.036	-10000	0	-0.19	9	9
PTPRO	0	0.1	-10000	0	-0.44	24	24
SH2B2	0.006	0.099	-10000	0	-0.41	24	24
DOK1	0.019	0	-10000	0	-10000	0	0
MATK	0.01	0.1	-10000	0	-0.41	24	24
CREBBP	0.031	0.029	-10000	0	-10000	0	0
BCL2	0.035	0.064	-10000	0	-10000	0	0

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	-0.001	0.078	-9999	-0.27	39	39
SVIL	0.008	0.038	-9999	-0.11	49	49
ZNF318	0.015	0.013	-9999	-0.12	5	5
JMJD2C	0.026	0	-9999	-10000	0	0
T-DHT/AR/Ubc9	0.027	0.029	-9999	-10000	0	0
CARM1	0.018	0.015	-9999	-0.2	2	2
PRDX1	0.012	0.044	-9999	-0.24	14	14
PELP1	0.014	0.035	-9999	-0.29	7	7
CTNNB1	0.018	0.023	-9999	-0.29	3	3
AKT1	0.004	0.063	-9999	-0.25	28	28
PTK2B	0.019	0.013	-9999	-0.11	5	5
MED1	-0.003	0.078	-9999	-0.29	36	36
MAK	0.01	0.026	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	-0.01	0.079	-9999	-0.18	79	79
GSN	0	0.065	-9999	-0.16	59	59
NCOA2	0.018	0.01	-9999	-10000	0	0
NCOA6	0.004	0.07	-9999	-0.28	29	29
DNA-PK	0.022	0.051	-9999	-0.19	25	25
NCOA4	0.014	0.038	-9999	-0.29	8	8
PIAS3	0.015	0.033	-9999	-0.18	12	12
cell proliferation	0.006	0.028	-9999	-10000	0	0
XRCC5	0.013	0.038	-9999	-0.27	9	9
UBE3A	0.019	0.027	-9999	-0.29	4	4
T-DHT/AR/SNURF	0.013	0.027	-9999	-10000	0	0
FHL2	-0.045	0.2	-9999	-0.74	37	37
RANBP9	0.012	0.05	-9999	-0.29	14	14
JMJD1A	0.022	0.062	-9999	-0.29	20	20
CDK6	0.019	0	-9999	-10000	0	0
TGFB1I1	-0.01	0.089	-9999	-0.25	58	58
T-DHT/AR/CyclinD1	0.004	0.059	-9999	-0.14	52	52
XRCC6	0.017	0.019	-9999	-0.29	2	2
T-DHT/AR	0.019	0.074	-9999	-0.15	46	46
CTDSP1	0.011	0.049	-9999	-0.27	15	15
CTDSP2	0.002	0.052	-9999	-0.15	50	50
BRCA1	0.019	0.015	-9999	-0.11	7	7
TCF4	-0.009	0.085	-9999	-0.28	47	47
CDKN2A	-0.02	0.059	-9999	-0.11	155	155
SRF	0.007	0.039	-9999	-0.12	37	37
NKX3-1	0.017	0.096	-9999	-0.44	20	20
KLK3	0.02	0.035	-9999	-10000	0	0
TMF1	0.015	0.034	-9999	-0.23	9	9
HNRNPA1	0.016	0.027	-9999	-0.29	4	4
AOF2	0.004	0.066	-9999	-0.22	37	37
APPL1	0.006	0.046	-9999	-0.19	25	25
T-DHT/AR/Caspase 8	0.023	0.032	-9999	-0.11	2	2
AR	0.014	0.03	-9999	-0.12	2	2
UBA3	0	0	-9999	-10000	0	0
PATZ1	0.018	0	-9999	-10000	0	0
PAWR	0.019	0	-9999	-10000	0	0
PRKDC	0.002	0.063	-9999	-0.2	40	40
PA2G4	0.014	0.031	-9999	-0.24	7	7
UBE2I	0.019	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	0.019	0.039	-9999	-0.13	18	18
RPS6KA3	0.015	0.032	-9999	-0.29	3	3
T-DHT/AR/ARA70	0.024	0.036	-9999	-0.15	8	8
LATS2	-0.001	0	-9999	-10000	0	0
T-DHT/AR/PRX1	0.02	0.035	-9999	-0.15	10	10
Cyclin D3/CDK11 p58	0.006	0.037	-9999	-0.15	24	24
VAV3	-0.022	0.091	-9999	-0.18	110	110
KLK2	0.027	0.031	-9999	-10000	0	0
CASP8	0.015	0.022	-9999	-0.11	15	15
T-DHT/AR/TIF2/CARM1	0.038	0.03	-9999	-0.13	1	1
TMPRSS2	0.016	0.096	-9999	-0.44	20	20
CCND1	-0.021	0.087	-9999	-0.17	111	111
PIAS1	0.011	0.056	-9999	-0.29	18	18
mol:T-DHT	0	0.016	-9999	-0.054	37	37
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.022	0.006	-9999	-10000	0	0
T-DHT/AR/CDK6	0.026	0.029	-9999	-10000	0	0
CMTM2	0	0	-9999	-10000	0	0
SNURF	0	0	-9999	-10000	0	0
ZMIZ1	-0.008	0.087	-9999	-0.28	47	47
CCND3	0.008	0.055	-9999	-0.23	24	24
TGIF1	-0.006	0.076	-9999	-0.22	54	54
FKBP4	0.016	0.029	-9999	-0.13	17	17

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	-0.029	0.12	0.25	7	-0.72	13	20
SMARCC2	0	0.074	-10000	0	-0.28	35	35
SMARCC1	0.012	0.038	-10000	0	-0.15	23	23
TBX21	0.039	0.036	-10000	0	-10000	0	0
SUMO2	0.02	0.007	-10000	0	-10000	0	0
STAT1 (dimer)	0.007	0.055	-10000	0	-0.17	36	36
FKBP4	0.014	0.029	-10000	0	-0.13	17	17
FKBP5	-0.023	0.087	-10000	0	-0.16	121	121
GR alpha/HSP90/FKBP51/HSP90	-0.01	0.067	-10000	0	-0.2	26	26
PRL	0.042	0.041	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/TIF2	-0.03	0.073	-10000	0	-0.32	1	1
RELA	-0.031	0.077	-10000	0	-0.15	138	138
FGG	-0.019	0.082	-10000	0	-0.31	2	2
GR beta/TIF2	-0.001	0.052	-10000	0	-0.23	9	9
IFNG	0.042	0.068	-10000	0	-10000	0	0
apoptosis	-0.001	0.21	0.47	23	-0.59	26	49
CREB1	0.024	0.036	-10000	0	-0.29	6	6
histone acetylation	0.024	0.043	-10000	0	-0.23	7	7
BGLAP	0.037	0.049	-10000	0	-10000	0	0
GR/PKAc	0.02	0.062	-10000	0	-0.2	20	20
NF kappa B1 p50/RelA	-0.055	0.13	-10000	0	-0.24	144	144
SMARCD1	0.018	0.013	-10000	0	-0.11	5	5
MDM2	-0.006	0.033	-10000	0	-0.13	1	1
GATA3	0.032	0.018	-10000	0	-10000	0	0
AKT1	0.005	0.066	0.16	13	-0.26	26	39
CSF2	0.028	0.032	-10000	0	-10000	0	0
GSK3B	0.005	0.066	-10000	0	-0.27	28	28
NR1I3	0.011	0.19	0.46	19	-0.51	23	42
CSN2	-0.016	0.073	-10000	0	-0.29	1	1
BRG1/BAF155/BAF170/BAF60A	0.021	0.079	-10000	0	-0.21	48	48
NFATC1	0.029	0	-10000	0	-10000	0	0
POU2F1	0.021	0.028	-10000	0	-0.24	3	3
CDKN1A	-0.15	0.44	-10000	0	-1.3	62	62
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.001	0.008	-10000	0	-10000	0	0
SFN	0.002	0.044	-10000	0	-0.11	70	70
GR alpha/HSP90/FKBP51/HSP90/14-3-3	-0.002	0.069	-10000	0	-0.19	32	32
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.055	0.3	0.46	10	-0.72	76	86
JUN	0.05	0.063	-10000	0	-0.26	2	2
IL4	0.045	0.035	-10000	0	-10000	0	0
CDK5R1	0.014	0.025	-10000	0	-0.11	16	16
PRKACA	0.019	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.028	0.073	-10000	0	-0.25	35	35
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.006	0.064	-10000	0	-0.19	19	19
cortisol/GR alpha (monomer)	-0.047	0.082	-10000	0	-0.38	1	1
NCOA2	0.018	0.01	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	0.007	0.076	-10000	0	-0.23	33	33
AP-1/NFAT1-c-4	0.062	0.1	-10000	0	-0.38	5	5
AFP	0.05	0.066	-10000	0	-10000	0	0
SUV420H1	-0.009	0.088	-10000	0	-0.28	49	49
IRF1	-0.027	0.14	-10000	0	-0.73	17	17
TP53	-0.04	0.18	-10000	0	-0.5	66	66
PPP5C	0.017	0.015	-10000	0	-0.11	7	7
KRT17	0.038	0.077	-10000	0	-10000	0	0
KRT14	0.026	0.048	0.39	1	-10000	0	1
TBP	0.023	0.031	-10000	0	-0.28	4	4
CREBBP	0.01	0.007	-10000	0	-10000	0	0
HDAC1	0.007	0.037	-10000	0	-0.22	12	12
HDAC2	0.003	0.061	-10000	0	-0.22	33	33
AP-1	0.062	0.1	-10000	0	-0.39	5	5
MAPK14	0.019	0.015	-10000	0	-0.11	5	5
MAPK10	-0.016	0.097	-10000	0	-0.26	67	67
MAPK11	0.02	0.007	-10000	0	-10000	0	0
KRT5	0.04	0.074	-10000	0	-10000	0	0
interleukin-1 receptor activity	-0.002	0	-10000	0	-10000	0	0
NCOA1	-0.006	0.084	-10000	0	-0.28	43	43
STAT1	0.007	0.055	-10000	0	-0.17	36	36
CGA	0.039	0.047	-10000	0	-0.35	1	1
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	-0.047	0.07	-10000	0	-0.42	8	8
MAPK3	0.02	0.01	-10000	0	-0.11	1	1
MAPK1	0.011	0.05	-10000	0	-0.22	21	21
ICAM1	-0.019	0.11	-10000	0	-10000	0	0
NFKB1	-0.033	0.082	-10000	0	-0.15	142	142
MAPK8	0.053	0.045	-10000	0	-10000	0	0
MAPK9	0.017	0.029	-10000	0	-0.23	6	6
cortisol/GR alpha (dimer)	-0.003	0.22	0.48	23	-0.62	27	50
BAX	-0.038	0.18	-10000	0	-1.4	5	5
POMC	0.035	0.06	-10000	0	-10000	0	0
EP300	0.002	0.046	-10000	0	-0.3	11	11
cortisol/GR alpha (dimer)/p53	-0.057	0.12	-10000	0	-0.43	17	17
proteasomal ubiquitin-dependent protein catabolic process	0.006	0.073	0.24	39	-10000	0	39
SGK1	-0.006	0.05	-10000	0	-0.31	11	11
IL13	0.048	0.058	-10000	0	-10000	0	0
IL6	-0.027	0.11	-10000	0	-10000	0	0
PRKACG	0.019	0	-10000	0	-10000	0	0
IL5	0.043	0.051	-10000	0	-10000	0	0
IL2	0.043	0.067	-10000	0	-10000	0	0
CDK5	0.006	0.06	-10000	0	-0.23	28	28
PRKACB	-0.002	0.076	-10000	0	-0.26	39	39
HSP90AA1	0.018	0.019	-10000	0	-0.29	2	2
IL8	-0.21	0.39	-10000	0	-0.85	138	138
CDK5R1/CDK5	0.015	0.049	-10000	0	-0.18	25	25
NF kappa B1 p50/RelA/PKAc	-0.018	0.11	-10000	0	-0.22	34	34
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	-0.011	0.081	-10000	0	-0.55	1	1
SMARCA4	-0.004	0.08	-10000	0	-0.29	37	37
chromatin remodeling	-0.024	0.12	-10000	0	-0.43	28	28
NF kappa B1 p50/RelA/Cbp	-0.032	0.11	-10000	0	-0.24	24	24
JUN (dimer)	0.05	0.063	-10000	0	-0.26	2	2
YWHAH	-0.006	0.082	-10000	0	-0.25	49	49
VIPR1	0.037	0.042	-10000	0	-10000	0	0
NR3C1	-0.019	0.069	-10000	0	-0.35	9	9
NR4A1	0.024	0.01	-10000	0	-10000	0	0
TIF2/SUV420H1	0.008	0.062	-10000	0	-0.19	46	46
MAPKKK cascade	-0.001	0.21	0.47	23	-0.59	26	49
cortisol/GR alpha (dimer)/Src-1	-0.034	0.097	-10000	0	-0.37	12	12
PBX1	0.021	0.032	-10000	0	-0.23	7	7
POU1F1	0.025	0.008	-10000	0	-10000	0	0
SELE	-0.011	0.11	-10000	0	-10000	0	0
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	-0.025	0.12	-10000	0	-0.43	28	28
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	-0.011	0.081	-10000	0	-0.55	1	1
mol:cortisol	-0.028	0.05	-10000	0	-0.2	1	1
MMP1	0.013	0.064	-10000	0	-10000	0	0

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	-0.014	0.078	-9999	-0.16	95	95
positive regulation of NF-kappaB transcription factor activity	0.005	0.055	-9999	-0.19	27	27
MAP2K4	0.021	0.049	-9999	-0.16	29	29
IKBKB	0.019	0	-9999	-10000	0	0
TNFRSF10B	0.015	0.022	-9999	-0.11	15	15
TNFRSF10A	0	0	-9999	-10000	0	0
SMPD1	0.005	0.034	-9999	-0.12	27	27
IKBKG	0.019	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
TNFRSF10D	0.019	0.006	-9999	-0.11	1	1
TRAIL/TRAILR2	0.003	0.057	-9999	-0.19	32	32
TRAIL/TRAILR3	0.005	0.055	-9999	-0.19	29	29
TRAIL/TRAILR1	-0.007	0.052	-9999	-0.11	95	95
TRAIL/TRAILR4	0.005	0.055	-9999	-0.19	27	27
TRAIL/TRAILR1/DAP3/GTP	0.003	0.049	-9999	-0.15	39	39
IKK complex	0.029	0.029	-9999	-0.27	2	2
RIPK1	0.016	0.019	-9999	-0.11	11	11
response to oxidative stress	0	0	-9999	-10000	0	0
DAP3/GTP	0.009	0.033	-9999	-0.19	14	14
MAPK3	-0.001	0.052	-9999	-0.19	27	27
MAP3K1	0.019	0.048	-9999	-0.17	29	29
TRAILR4 (trimer)	0.019	0.006	-9999	-0.11	1	1
TRADD	0.019	0	-9999	-10000	0	0
TRAILR1 (trimer)	0	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.014	0.045	-9999	-0.16	29	29
CFLAR	0.016	0.024	-9999	-0.15	9	9
MAPK1	-0.007	0.062	-9999	-0.2	41	41
TRAIL/TRAILR1/FADD/TRADD/RIP	0.025	0.046	-9999	-0.12	29	29
mol:ceramide	0.005	0.034	-9999	-0.12	27	27
FADD	0.017	0.021	-9999	-0.2	4	4
MAPK8	0.024	0.047	-9999	-0.19	8	8
TRAF2	0.019	0	-9999	-10000	0	0
TRAILR3 (trimer)	0.019	0.008	-9999	-0.11	2	2
CHUK	0.016	0.024	-9999	-0.15	9	9
TRAIL/TRAILR1/FADD	0.006	0.047	-9999	-0.16	30	30
DAP3	0.011	0.048	-9999	-0.28	14	14
CASP10	-0.002	0.049	-9999	-0.19	29	29
JNK cascade	0.005	0.055	-9999	-0.19	27	27
TRAIL (trimer)	-0.014	0.078	-9999	-0.16	95	95
TNFRSF10C	0.019	0.008	-9999	-0.11	2	2
TRAIL/TRAILR1/DAP3/GTP/FADD	0.012	0.05	-9999	-0.14	40	40
TRAIL/TRAILR2/FADD	0.015	0.052	-9999	-0.15	35	35
cell death	0.005	0.034	-9999	-0.12	27	27
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.019	0.046	-9999	-0.15	29	29
TRAILR2 (trimer)	0.015	0.022	-9999	-0.11	15	15
CASP8	0.014	0.022	-9999	-10000	0	0
negative regulation of caspase activity	0	0	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.033	0.05	-9999	-0.12	29	29

×

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

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
BAG4	0.018	0.011	-9999	-0.11	4	4
Caspase 8 (4 units)	0.005	0.09	-9999	-0.31	20	20
NEF	0.005	0	-9999	-10000	0	0
NFKBIA	-0.001	0.067	-9999	-0.24	34	34
BIRC3	0.006	0.064	-9999	-0.21	14	14
CYCS	-0.004	0.088	-9999	-0.28	30	30
RIPK1	0.016	0.019	-9999	-0.11	11	11
CD247	0.022	0.015	-9999	-0.1	7	7
MAP2K7	0.006	0.098	-9999	-0.41	15	15
protein ubiquitination	0.026	0.064	-9999	-0.21	17	17
CRADD	0.017	0.015	-9999	-0.11	7	7
DAXX	0.017	0.018	-9999	-0.15	5	5
FAS	-0.027	0.099	-9999	-0.2	111	111
BID	-0.007	0.09	-9999	-0.28	31	31
NF-kappa-B/RelA/I kappa B alpha	0.021	0.063	-9999	-0.16	38	38
TRADD	0.019	0	-9999	-10000	0	0
MAP3K5	-0.014	0.091	-9999	-0.25	65	65
CFLAR	0.016	0.024	-9999	-0.15	9	9
FADD	0.017	0.021	-9999	-0.2	4	4
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.021	0.063	-9999	-0.16	38	38
MAPK8	0.01	0.093	-9999	-0.38	15	15
APAF1	0.019	0	-9999	-10000	0	0
TRAF1	0.017	0.015	-9999	-0.11	7	7
TRAF2	0.019	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.006	0.088	-9999	-0.3	22	22
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.022	0.076	-9999	-0.26	19	19
CHUK	0.026	0.067	-9999	-0.23	17	17
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.009	0.08	-9999	-0.14	93	93
TCRz/NEF	0.024	0.01	-9999	-10000	0	0
TNF	0.018	0.01	-9999	-0.11	3	3
FASLG	0.027	0.008	-9999	-10000	0	0
NFKB1	0.01	0.04	-9999	-0.22	12	12
TNFR1A/BAG4/TNF-alpha	0.02	0.057	-9999	-0.15	50	50
CASP6	0.007	0.11	-9999	-0.45	19	19
CASP7	0.002	0.11	-9999	-0.33	28	28
RELA	0.014	0.025	-9999	-0.24	3	3
CASP2	0.017	0.017	-9999	-0.11	9	9
CASP3	0.004	0.1	-9999	-0.32	25	25
TNFRSF1A	-0.01	0.091	-9999	-0.29	50	50
TNFR1A/BAG4	0.007	0.065	-9999	-0.19	50	50
CASP8	0.015	0.022	-9999	-0.11	15	15
CASP9	0.014	0.029	-9999	-0.13	18	18
MAP3K14	0.024	0.072	-9999	-0.24	18	18
APAF-1/Caspase 9	-0.028	0.067	-9999	-0.23	36	36
BCL2	0.015	0.087	-9999	-0.35	15	15

×

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	0.023	0.034	-9999	-0.11	25	25
TC10/GTP	0.023	0.035	-9999	-0.13	25	25
Insulin Receptor/Insulin/IRS1/Shp2	0.034	0.049	-9999	-0.14	31	31
HRAS	0.009	0.055	-9999	-0.28	18	18
APS homodimer	0	0	-9999	-10000	0	0
GRB14	0.001	0.047	-9999	-0.29	2	2
FOXO3	-0.031	0.18	-9999	-0.79	28	28
AKT1	-0.006	0.083	-9999	-0.23	43	43
INSR	0.019	0.007	-9999	-10000	0	0
Insulin Receptor/Insulin	0.039	0.064	-9999	-0.34	10	10
mol:GTP	0	0	-9999	-10000	0	0
GRB10	-0.018	0.091	-9999	-0.2	89	89
SORBS1	0.019	0	-9999	-10000	0	0
CRK	0.009	0.053	-9999	-0.28	17	17
PTPN1	0.014	0.058	-9999	-0.33	10	10
CAV1	-0.002	0.058	-9999	-0.19	36	36
CBL/APS/CAP/Crk-II/C3G	0.04	0.029	-9999	-0.12	16	16
Insulin Receptor/Insulin/IRS1/NCK2	0.031	0.058	-9999	-0.16	37	37
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.078	-9999	-0.15	99	99
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.021	0.07	-9999	-0.35	14	14
RPS6KB1	-0.003	0.077	-9999	-0.22	41	41
PARD6A	0.015	0.026	-9999	-0.14	12	12
CBL	0.019	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0.02	0.013	-9999	-10000	0	0
PIK3R1	-0.015	0.095	-9999	-0.27	62	62
Insulin Receptor/Insuli/IRS1/GRB2/Shc	0.005	0.084	-9999	-0.25	36	36
HRAS/GTP	-0.015	0.04	-9999	-0.17	20	20
Insulin Receptor	0.019	0.007	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.033	0.058	-9999	-0.14	40	40
PRKCI	0.01	0.095	-9999	-0.48	17	17
Insulin Receptor/Insulin/GRB14/PDK1	-0.03	0.06	-9999	-0.21	36	36
SHC1	0.004	0.052	-9999	-0.14	48	48
negative regulation of MAPKKK cascade	0.028	0.045	-9999	-0.26	5	5
PI3K	0.006	0.082	-9999	-0.15	99	99
NCK2	0.009	0.053	-9999	-0.28	17	17
RHOQ	0.011	0.048	-9999	-0.28	14	14
mol:H2O2	-0.002	0.007	-9999	-10000	0	0
HRAS/GDP	0.007	0.037	-9999	-0.19	18	18
AKT2	-0.001	0.069	-9999	-0.19	36	36
PRKCZ	-0.017	0.082	-9999	-0.47	16	16
SH2B2	0	0	-9999	-10000	0	0
SHC/SHIP	0.01	0.042	-9999	-0.13	33	33
F2RL2	0.019	0.008	-9999	-0.11	2	2
TRIP10	0.015	0.029	-9999	-0.15	13	13
Insulin Receptor/Insulin/Shc	0.028	0.033	-9999	-0.15	9	9
TC10/GTP/CIP4/Exocyst	0.019	0.033	-9999	-0.16	16	16
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.034	0.04	-9999	-0.15	16	16
RAPGEF1	0.019	0	-9999	-10000	0	0
RASA1	0.003	0.069	-9999	-0.28	29	29
NCK1	0.014	0.036	-9999	-0.19	14	14
CBL/APS/CAP/Crk-II	0.032	0.03	-9999	-0.14	16	16
TC10/GDP	0.009	0.033	-9999	-0.19	14	14
Insulin Receptor/Insulin/SHC/GRB10	0.018	0.065	-9999	-0.15	51	51
INPP5D	0.005	0.034	-9999	-0.13	25	25
SOS1	0	0	-9999	-10000	0	0
SGK1	-0.003	0.007	-9999	-10000	0	0
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.015	0.033	-9999	-0.26	7	7
IRS1	-0.003	0.071	-9999	-0.19	54	54
p62DOK/RasGAP	0.028	0.045	-9999	-0.26	5	5
INS	0.019	0.007	-9999	-10000	0	0
mol:PI-3-4-P2	0.005	0.033	-9999	-0.13	25	25
GRB2	0.014	0.039	-9999	-0.26	10	10
EIF4EBP1	-0.006	0.082	-9999	-0.23	44	44
PTPRA	0.017	0.024	-9999	-0.22	4	4
PIK3CA	-0.011	0.085	-9999	-0.22	65	65
TC10/GTP/CIP4	0.019	0.033	-9999	-0.16	16	16
PDPK1	0.019	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.011	0.056	-9999	-0.17	40	40
Insulin Receptor/Insulin/IRS1	0.024	0.043	-9999	-0.14	25	25
Insulin Receptor/Insulin/IRS3	0.028	0.014	-9999	-10000	0	0
Par3/Par6	0.036	0.033	-9999	-0.12	18	18

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.027	0.037	-9999	-0.11	28	28
E-cadherin/beta catenin	0.022	0.026	-9999	-0.19	3	3
CTNNB1	0.017	0.023	-9999	-0.29	3	3
JUP	0.007	0.037	-9999	-0.11	47	47
CDH1	0.012	0.029	-9999	-0.11	28	28

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	-0.004	0.079	-10000	0	-0.29	36	36
SMAD2	0.003	0.051	0.2	2	-0.21	19	21
SMAD3	0.019	0.064	-10000	0	-0.35	10	10
SMAD3/SMAD4	-0.011	0.18	-10000	0	-0.5	51	51
SMAD4/Ubc9/PIASy	0.024	0.049	-10000	0	-0.15	36	36
SMAD2/SMAD2/SMAD4	0.016	0.091	-10000	0	-0.31	22	22
PPM1A	0.017	0.023	-10000	0	-0.29	3	3
CALM1	0.007	0.056	-10000	0	-0.21	28	28
SMAD2/SMAD4	0.009	0.056	-10000	0	-0.21	24	24
MAP3K1	0.015	0.022	-10000	0	-0.11	16	16
TRAP-1/SMAD4	0.009	0.06	-10000	0	-0.19	43	43
MAPK3	0.019	0.006	-10000	0	-10000	0	0
MAPK1	0.009	0.051	-10000	0	-0.22	22	22
NUP214	0.019	0	-10000	0	-10000	0	0
CTDSP1	0.011	0.049	-10000	0	-0.27	15	15
CTDSP2	0.004	0.052	-10000	0	-0.14	50	50
CTDSPL	0.019	0.006	-10000	0	-0.11	1	1
KPNB1	0.007	0.059	-10000	0	-0.28	21	21
TGFBRAP1	0.015	0.033	-10000	0	-0.26	7	7
UBE2I	0.019	0	-10000	0	-10000	0	0
NUP153	0.004	0.065	-10000	0	-0.26	28	28
KPNA2	-0.001	0.074	-10000	0	-0.26	37	37
PIAS4	0.019	0.006	-10000	0	-10000	0	0

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.004	0.17	-10000	0	-1.1	12	12
CLOCK	0.009	0.054	-10000	0	-0.22	25	25
TIMELESS/CRY2	0.001	0.18	-10000	0	-1.1	12	12
DEC1/BMAL1	0.005	0.065	-10000	0	-0.19	49	49
ATR	0.011	0.049	-10000	0	-0.26	16	16
NR1D1	0.013	0.07	-10000	0	-0.48	2	2
ARNTL	-0.014	0.093	-10000	0	-0.28	53	53
TIMELESS	-0.007	0.18	-10000	0	-1.2	12	12
NPAS2	0.018	0.019	-10000	0	-0.11	9	9
CRY2	0.017	0.016	-10000	0	-0.11	8	8
mol:CO	-0.006	0.024	0.14	12	-10000	0	12
CHEK1	0.005	0.046	-10000	0	-0.13	48	48
mol:HEME	0.006	0.024	-10000	0	-0.14	12	12
PER1	-0.004	0.078	-10000	0	-0.25	45	45
BMAL/CLOCK/NPAS2	0.017	0.076	-10000	0	-0.16	67	67
BMAL1/CLOCK	-0.01	0.14	-10000	0	-0.56	20	20
S phase of mitotic cell cycle	0.004	0.17	-10000	0	-1.1	12	12
TIMELESS/CHEK1/ATR	0.003	0.18	-10000	0	-1.1	12	12
mol:NADPH	0.006	0.024	-10000	0	-0.14	12	12
PER1/TIMELESS	-0.005	0.18	-10000	0	-1.1	12	12
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.019	0	-10000	0	-10000	0	0

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.02	0.033	-9999	-0.15	16	16
NFATC2	0.009	0.032	-9999	-0.16	16	16
NFATC3	0.02	0.033	-9999	-0.15	16	16
CD40LG	0.045	0.084	-9999	-0.27	12	12
PTGS2	0.036	0.093	-9999	-0.28	14	14
JUNB	-0.003	0.067	-9999	-0.17	63	63
CaM/Ca2+/Calcineurin A alpha-beta B1	0.011	0.038	-9999	-0.2	16	16
CaM/Ca2+	0.011	0.038	-9999	-0.2	16	16
CALM1	0.009	0.056	-9999	-0.29	16	16
JUN	0.002	0.077	-9999	-0.27	37	37
mol:Ca2+	0.002	0.003	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.008	0.029	-9999	-0.096	31	31
FOSL1	0.006	0.038	-9999	-0.11	51	51
CREM	0.017	0.014	-9999	-0.11	6	6
Jun/NFAT1-c-4/p21SNFT	0.055	0.061	-9999	-0.21	14	14
FOS	-0.042	0.11	-9999	-0.21	146	146
IFNG	0.045	0.084	-9999	-0.27	13	13
AP-1/NFAT1-c-4	0.083	0.11	-9999	-0.31	12	12
FASLG	0.045	0.084	-9999	-0.27	12	12
NFAT1-c-4/ICER1	0.043	0.034	-9999	-0.13	7	7
IL2RA	0.043	0.087	-9999	-0.27	13	13
FKBP12/FK506	0.006	0.035	-9999	-0.12	31	31
CSF2	0.045	0.084	-9999	-0.27	12	12
JunB/Fra1/NFAT1-c-4	0.04	0.053	-9999	-0.15	10	10
IL4	0.045	0.084	-9999	-0.27	12	12
IL2	0.005	0.009	-9999	-10000	0	0
IL3	0.009	0.05	-9999	-0.75	2	2
FKBP1A	0.007	0.052	-9999	-0.18	31	31
BATF3	0	0	-9999	-10000	0	0
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.022	0.028	-9999	-0.29	2	2

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	0.014	0.043	-10000	0	-0.2	14	14
CRKL	0.015	0.078	-10000	0	-0.47	12	12
mol:PIP3	-0.01	0.037	0.21	10	-10000	0	10
AKT1	-0.005	0.038	0.2	6	-0.15	20	26
PTK2B	0.018	0.013	-10000	0	-0.11	5	5
RAPGEF1	0.018	0.074	-10000	0	-0.44	12	12
RANBP10	0.019	0	-10000	0	-10000	0	0
PIK3CA	-0.011	0.085	-10000	0	-0.22	65	65
HGF/MET/SHIP2	0.027	0.035	-10000	0	-0.14	10	10
MAP3K5	0.014	0.084	-10000	0	-0.36	17	17
HGF/MET/CIN85/CBL/ENDOPHILINS	0.028	0.025	-10000	0	-0.093	4	4
AP1	-0.027	0.092	-10000	0	-0.2	97	97
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.004	0.052	-10000	0	-0.14	48	48
apoptosis	-0.12	0.31	-10000	0	-0.78	93	93
STAT3 (dimer)	0.015	0.072	-10000	0	-0.23	36	36
GAB1/CRKL/SHP2/PI3K	0.013	0.11	-10000	0	-0.39	24	24
INPP5D	0	0	-10000	0	-10000	0	0
CBL/CRK	0.021	0.082	-10000	0	-0.41	14	14
PTPN11	0.015	0.033	-10000	0	-0.26	7	7
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.017	0.025	-10000	0	-0.22	5	5
PTEN	0.013	0.037	-10000	0	-0.18	16	16
ELK1	-0.001	0.04	0.23	13	-10000	0	13
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	0.016	0.043	-10000	0	-0.17	19	19
PAK1	-0.001	0.037	0.21	5	-0.14	19	24
HGF/MET/RANBP10	0.029	0.028	-10000	0	-0.1	4	4
HRAS	0.011	0.098	-10000	0	-0.52	14	14
DOCK1	0.015	0.078	-10000	0	-0.45	12	12
GAB1	0.011	0.082	-10000	0	-0.49	12	12
CRK	0.011	0.084	-10000	0	-0.42	15	15
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	0.016	0.08	-10000	0	-0.44	14	14
JUN	-0.002	0.077	-10000	0	-0.28	37	37
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	0.012	0.014	-10000	0	-10000	0	0
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
cell morphogenesis	0.008	0.099	-10000	0	-0.29	38	38
GRB2/SHC	0.024	0.037	-10000	0	-0.13	15	15
FOS	-0.046	0.12	-10000	0	-0.22	146	146
GLMN	0.002	0.016	0.086	2	-0.19	3	5
cell motility	-0.001	0.04	0.23	13	-10000	0	13
HGF/MET/MUC20	0.017	0.025	-10000	0	-0.11	4	4
cell migration	0.023	0.036	-10000	0	-0.13	15	15
GRB2	0.014	0.039	-10000	0	-0.26	10	10
CBL	0.019	0	-10000	0	-10000	0	0
MET/RANBP10	0.02	0.026	-10000	0	-10000	0	0
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.016	0.062	-10000	0	-0.2	35	35
MET/MUC20	0.007	0.024	-10000	0	-0.07	47	47
RAP1B	0.018	0.07	-10000	0	-0.41	12	12
RAP1A	0.022	0.071	-10000	0	-0.41	12	12
HGF/MET/RANBP9	0.025	0.04	-10000	0	-0.14	18	18
RAF1	0.01	0.1	-10000	0	-0.47	19	19
STAT3	0.015	0.073	-10000	0	-0.24	36	36
cell proliferation	0.019	0.068	-10000	0	-0.29	16	16
RPS6KB1	0.013	0.011	-10000	0	-10000	0	0
MAPK3	-0.014	0.016	-10000	0	-10000	0	0
MAPK1	0.005	0.11	0.71	13	-10000	0	13
RANBP9	0.011	0.05	-10000	0	-0.29	14	14
MAPK8	0.019	0.082	-10000	0	-0.33	17	17
SRC	0.019	0.058	-10000	0	-0.18	35	35
PI3K	0.003	0.067	-10000	0	-0.14	82	82
MET/Glomulin	0.009	0.025	-10000	0	-0.15	4	4
SOS1	0	0	-10000	0	-10000	0	0
MAP2K1	0.013	0.1	-10000	0	-0.46	19	19
MET	0.007	0.037	-10000	0	-0.11	47	47
MAP4K1	0.023	0.076	-10000	0	-0.44	12	12
PTK2	0.009	0.054	-10000	0	-0.27	18	18
MAP2K2	0.014	0.099	-10000	0	-0.44	19	19
BAD	-0.003	0.041	0.21	5	-0.15	23	28
MAP2K4	0.016	0.08	-10000	0	-0.33	18	18
SHP2/GRB2/SOS1/GAB1	-0.013	0.067	-10000	0	-0.35	18	18
INPPL1	0.016	0.033	-10000	0	-0.29	6	6
PXN	0.018	0.011	-10000	0	-0.11	4	4
SH3KBP1	0	0	-10000	0	-10000	0	0
HGS	0.013	0.017	-10000	0	-0.16	2	2
PLCgamma1/PKC	0.013	0.017	-10000	0	-0.15	5	5
HGF	0.016	0.02	-10000	0	-0.11	13	13
RASA1	0.003	0.069	-10000	0	-0.28	29	29
NCK1	0.014	0.036	-10000	0	-0.19	14	14
PTPRJ	0.019	0	-10000	0	-10000	0	0
NCK/PLCgamma1	0.031	0.027	-10000	0	-0.13	7	7
PDPK1	-0.004	0.031	0.19	9	-10000	0	9
HGF/MET/SHIP	0.017	0.025	-10000	0	-0.11	4	4

×

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	0.013	0.04	-10000	0	-0.22	13	13
HDAC3	0.018	0.013	-10000	0	-0.29	1	1
VDR	0.019	0.008	-10000	0	-0.11	2	2
Cbp/p300/PCAF	0.021	0.027	-10000	0	-0.16	11	11
EP300	0.012	0.046	-10000	0	-0.24	15	15
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.032	0.034	-10000	0	-0.21	5	5
KAT2B	0	0	-10000	0	-10000	0	0
MAPK14	0.018	0.013	-10000	0	-0.11	5	5
AKT1	0.045	0.073	0.18	87	-0.18	16	103
RAR alpha/9cRA/Cyclin H	0.021	0.085	-10000	0	-0.27	25	25
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.024	0.055	-10000	0	-0.26	16	16
CDC2	-0.03	0.099	-10000	0	-0.19	123	123
response to UV	-0.001	0.007	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.023	0.022	-10000	0	-10000	0	0
NCOR2	0.019	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.014	0.005	-10000	0	-0.07	2	2
RXRs/RARs/NRIP1/9cRA	0.019	0.15	-10000	0	-0.52	35	35
NCOA2	0.018	0.01	-10000	0	-10000	0	0
NCOA3	0.018	0.013	-10000	0	-0.11	5	5
NCOA1	-0.006	0.083	-10000	0	-0.28	43	43
VDR/VDR/DNA	0.019	0.008	-10000	0	-0.11	2	2
RARG	0.019	0.005	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.025	0.004	-10000	0	-10000	0	0
MAPK3	0.018	0.008	-10000	0	-10000	0	0
MAPK1	0.009	0.051	-10000	0	-0.22	22	22
MAPK8	0.018	0.009	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.018	0.097	-10000	0	-0.32	35	35
RARA	0.023	0.024	-10000	0	-10000	0	0
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.031	0.028	-10000	0	-0.2	5	5
PRKCA	0.018	0.016	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	0.007	0.16	-10000	0	-0.59	35	35
RXRG	0.023	0.026	-10000	0	-10000	0	0
RXRA	0.004	0.074	-10000	0	-0.26	14	14
RXRB	0.024	0.024	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.014	0.005	-10000	0	-0.07	2	2
RBP1	-0.051	0.12	-10000	0	-0.24	146	146
CRBP1/9-cic-RA	-0.033	0.083	-10000	0	-0.16	146	146
RARB	0.019	0.01	-10000	0	-0.11	2	2
PRKCG	0.018	0.016	-10000	0	-10000	0	0
MNAT1	0.015	0.033	-10000	0	-0.19	11	11
RAR alpha/RXRs	0.039	0.12	-10000	0	-0.37	26	26
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.038	0.081	-10000	0	-0.26	24	24
proteasomal ubiquitin-dependent protein catabolic process	0.034	0.033	-10000	0	-0.16	5	5
RXRs/RARs/NRIP1/9cRA/HDAC3	0.007	0.16	-10000	0	-0.59	35	35
positive regulation of DNA binding	0.014	0.078	-10000	0	-0.25	25	25
NRIP1	-0.027	0.29	-10000	0	-1.1	35	35
RXRs/RARs	0.017	0.12	-10000	0	-0.41	35	35
RXRs/RXRs/DNA/9cRA	0.008	0.097	-10000	0	-0.33	35	35
PRKACA	0.019	0	-10000	0	-10000	0	0
CDK7	0.011	0.048	-10000	0	-0.29	12	12
TFIIH	0.027	0.056	-10000	0	-0.2	24	24
RAR alpha/9cRA	0.039	0.05	-10000	0	-0.24	10	10
CCNH	0.011	0.048	-10000	0	-0.28	14	14
CREBBP	0.019	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	0.028	0.044	-10000	0	-0.15	23	23

×

JNK signaling in the CD4+ TCR pathway

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
LAT/GRAP2/SLP76/HPK1	0.03	0.051	-9999	-0.13	40	40
MAP4K1	0.019	0.006	-9999	-0.11	1	1
MAP3K8	0.004	0.042	-9999	-0.11	62	62
PRKCB	0	0	-9999	-10000	0	0
DBNL	0	0	-9999	-10000	0	0
CRKL	0.018	0.01	-9999	-0.11	3	3
MAP3K1	0.013	0.055	-9999	-0.22	6	6
JUN	0.01	0.041	-9999	-0.22	1	1
MAP3K7	0.012	0.063	-9999	-0.24	15	15
GRAP2	0.019	0	-9999	-10000	0	0
CRK	0.009	0.053	-9999	-0.28	17	17
MAP2K4	0.012	0.063	-9999	-0.21	17	17
LAT	0.018	0.014	-9999	-0.11	6	6
LCP2	-0.012	0.085	-9999	-0.21	70	70
MAPK8	0.016	0.018	-9999	-10000	0	0
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.012	0.058	-9999	-0.16	40	40
LAT/GRAP2/SLP76/HPK1/HIP-55	0.028	0.048	-9999	-0.12	40	40

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	0.017	0.018	-9999	-0.11	10	10
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.019	0	-9999	-10000	0	0
TCEB1	0.014	0.041	-9999	-0.27	10	10
HIF1A/p53	0.018	0.044	-9999	-0.19	14	14
HIF1A	0.013	0.035	-9999	-0.2	8	8
COPS5	0.016	0.03	-9999	-0.29	5	5
VHL/Elongin B/Elongin C/RBX1/CUL2	0.032	0.053	-9999	-0.15	33	33
FIH (dimer)	0.019	0	-9999	-10000	0	0
CDKN2A	-0.019	0.059	-9999	-0.11	155	155
ARNT/IPAS	0.026	0.013	-9999	-10000	0	0
HIF1AN	0.019	0	-9999	-10000	0	0
GNB2L1	0.018	0.019	-9999	-0.29	2	2
HIF1A/ARNT	0.024	0.035	-9999	-0.18	8	8
CUL2	0.005	0.064	-9999	-0.26	27	27
OS9	-0.005	0.069	-9999	-0.17	67	67
RACK1/Elongin B/Elongin C	0.035	0.029	-9999	-0.17	10	10
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.024	0.038	-9999	-0.19	9	9
PHD1-3/OS9	0.016	0.067	-9999	-0.17	42	42
HIF1A/RACK1/Elongin B/Elongin C	0.038	0.042	-9999	-0.2	7	7
VHL	0	0	-9999	-10000	0	0
HSP90AA1	0.018	0.019	-9999	-0.29	2	2
HIF1A/JAB1	0.023	0.039	-9999	-0.19	11	11
EGLN3	-0.004	0.065	-9999	-0.15	71	71
EGLN2	0.019	0	-9999	-10000	0	0
EGLN1	0.009	0.051	-9999	-0.24	20	20
TP53	-0.007	0.077	-9999	-0.2	62	62
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.015	0.095	-9999	-0.57	11	11
ARNT	0.019	0.006	-9999	-0.11	1	1
ARD1A	0.018	0.017	-9999	-0.16	4	4
RBX1	0.014	0.041	-9999	-0.27	10	10
HIF1A/p19ARF	0.008	0.045	-9999	-0.2	9	9

×

IL12-mediated signaling events

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
IL12/IL12R/TYK2/JAK2/SOCS1	0.036	0.064	-10000	0	-0.21	15	15
TBX21	0.015	0.17	-10000	0	-0.64	5	5
B2M	0.017	0.027	-10000	0	-0.29	4	4
TYK2	0.008	0.066	-10000	0	-0.3	21	21
IL12RB1	0.02	0.018	-10000	0	-0.13	1	1
GADD45B	-0.016	0.28	-10000	0	-1.1	25	25
IL12RB2	0.021	0.017	-10000	0	-10000	0	0
GADD45G	0.019	0.16	-10000	0	-0.54	8	8
natural killer cell activation	0.002	0.015	-10000	0	-10000	0	0
RELB	0.018	0.011	-10000	0	-0.11	4	4
RELA	0.018	0.02	-10000	0	-0.23	3	3
IL18	0	0.058	-10000	0	-0.13	70	70
IL2RA	0.012	0.029	-10000	0	-0.11	28	28
IFNG	0.018	0.01	-10000	0	-0.11	3	3
STAT3 (dimer)	0.01	0.21	-10000	0	-0.59	31	31
HLA-DRB5	-0.003	0.008	-10000	0	-10000	0	0
FASLG	0.015	0.17	-10000	0	-0.63	6	6
NF kappa B2 p52/RelB	0.017	0.16	-10000	0	-0.53	15	15
CD4	-0.007	0.071	-10000	0	-0.19	56	56
SOCS1	0.019	0	-10000	0	-10000	0	0
EntrezGene:6955	-0.003	0.009	-10000	0	-10000	0	0
CD3D	0.005	0.036	-10000	0	-0.12	40	40
CD3E	0.015	0.013	-10000	0	-0.13	1	1
CD3G	0.012	0.022	-10000	0	-0.12	11	11
IL12Rbeta2/JAK2	0.028	0.034	-10000	0	-10000	0	0
CCL3	0.008	0.17	-10000	0	-0.53	16	16
CCL4	-0.042	0.31	-10000	0	-1	36	36
HLA-A	0.012	0.046	-10000	0	-0.29	12	12
IL18/IL18R	0.04	0.053	-10000	0	-0.14	15	15
NOS2	0.012	0.16	-10000	0	-0.46	20	20
IL12/IL12R/TYK2/JAK2/SPHK2	0.036	0.064	-10000	0	-0.21	15	15
IL1R1	0.014	0.17	-10000	0	-0.64	5	5
IL4	0.017	0.015	-10000	0	-10000	0	0
JAK2	0.015	0.032	-10000	0	-0.11	23	23
EntrezGene:6957	-0.003	0.008	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	0.016	0.039	-10000	0	-0.17	11	11
RAB7A	0.009	0.24	-10000	0	-0.8	30	30
lysosomal transport	0.012	0.23	-10000	0	-0.74	31	31
FOS	-0.17	0.46	-10000	0	-1.2	85	85
STAT4 (dimer)	0.028	0.19	-10000	0	-0.56	23	23
STAT5A (dimer)	0.017	0.16	-10000	0	-0.52	16	16
GZMA	0.01	0.17	-10000	0	-0.64	6	6
GZMB	0.011	0.17	-10000	0	-0.64	6	6
HLX	0.015	0.023	-10000	0	-0.11	17	17
LCK	0.011	0.17	-10000	0	-0.55	16	16
TCR/CD3/MHC II/CD4	-0.045	0.12	-10000	0	-0.24	103	103
IL2/IL2R	0.039	0.032	-10000	0	-0.096	13	13
MAPK14	0.01	0.23	-10000	0	-0.73	30	30
CCR5	0.02	0.17	-10000	0	-1	3	3
IL1B	-0.008	0.068	-10000	0	-0.14	96	96
STAT6	0.019	0.071	-10000	0	-0.25	1	1
STAT4	0.012	0.03	-10000	0	-0.11	30	30
STAT3	-0.003	0.079	-10000	0	-0.29	37	37
STAT1	0.008	0.04	-10000	0	-0.12	40	40
NFKB1	0.014	0.038	-10000	0	-0.22	12	12
NFKB2	0.019	0.008	-10000	0	-0.11	2	2
IL12B	0.021	0.017	-10000	0	-10000	0	0
CD8A	0	0	-10000	0	-10000	0	0
CD8B	0.018	0.011	-10000	0	-0.11	4	4
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.036	0.064	0.21	15	-10000	0	15
IL2RB	0.014	0.024	-10000	0	-0.11	19	19
proteasomal ubiquitin-dependent protein catabolic process	0.03	0.18	-10000	0	-0.53	23	23
IL2RG	0.013	0.027	-10000	0	-0.11	24	24
IL12	0.032	0.027	-10000	0	-10000	0	0
STAT5A	0.019	0.008	-10000	0	-0.11	2	2
CD247	0.014	0.018	-10000	0	-0.11	7	7
IL2	0.019	0.006	-10000	0	-0.11	1	1
SPHK2	0.019	0	-10000	0	-10000	0	0
FRAP1	0.019	0.006	-10000	0	-0.11	1	1
IL12A	0.02	0.017	-10000	0	-10000	0	0
IL12/IL12R/TYK2/JAK2	0.009	0.18	-10000	0	-0.58	16	16
MAP2K3	0.01	0.21	-10000	0	-0.69	26	26
RIPK2	0.017	0.021	-10000	0	-0.18	5	5
MAP2K6	0.01	0.21	-10000	0	-0.66	29	29
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.051	0.12	-10000	0	-0.23	140	140
IL18RAP	0.019	0.017	-10000	0	-0.11	7	7
IL12Rbeta1/TYK2	0.021	0.053	-10000	0	-0.22	20	20
EOMES	-0.001	0.021	0.062	2	-10000	0	2
STAT1 (dimer)	0.028	0.16	-10000	0	-0.48	17	17
T cell proliferation	0.018	0.16	-10000	0	-0.48	24	24
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.019	0.014	-10000	0	-0.11	4	4
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.051	0.14	-10000	0	-0.54	27	27
ATF2	0.014	0.21	-10000	0	-0.67	30	30

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	0.017	0.069	-9999	-0.25	23	23
CaM/Ca2+	0.006	0.038	-9999	-0.2	16	16
AKT1	0.005	0.063	-9999	-0.25	28	28
AKT2	0.019	0	-9999	-10000	0	0
STXBP4	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
mol:glucose	0.007	0.069	-9999	-0.28	21	21
YWHAZ	0.014	0.037	-9999	-0.29	7	7
CALM1	0.007	0.056	-9999	-0.21	28	28
YWHAQ	0.018	0.019	-9999	-0.29	2	2
TBC1D4	0.009	0.045	-9999	-0.19	23	23
mol:Ca2+	0	0	-9999	-10000	0	0
YWHAH	-0.006	0.082	-9999	-0.25	49	49
YWHAB	0.015	0.035	-9999	-0.29	7	7
SNARE/Synip	0.014	0.041	-9999	-0.17	19	19
YWHAG	0	0	-9999	-10000	0	0
ASIP	0.019	0	-9999	-10000	0	0
PRKCI	0.015	0.028	-9999	-0.14	15	15
AS160/CaM/Ca2+	0.006	0.038	-9999	-0.2	16	16
RHOQ	0.011	0.048	-9999	-0.28	14	14
GYS1	-0.003	0.11	-9999	-0.41	31	31
PRKCZ	0	0	-9999	-10000	0	0
TRIP10	0.015	0.029	-9999	-0.15	13	13
TC10/GTP/CIP4/Exocyst	0.019	0.033	-9999	-0.16	16	16
AS160/14-3-3	0.002	0.12	-9999	-0.43	23	23
VAMP2	0.006	0.048	-9999	-0.15	40	40
SLC2A4	0.006	0.076	-9999	-0.3	21	21
STX4	0.011	0.048	-9999	-0.29	13	13
GSK3B	0.003	0.095	-9999	-0.35	31	31
SFN	0.002	0.044	-9999	-0.11	70	70
LNPEP	0.018	0.011	-9999	-0.11	4	4
YWHAE	0.011	0.045	-9999	-0.21	19	19

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	0.02	0.086	-9999	-0.2	58	58
Ran/GTP/Exportin 1/HDAC1	-0.008	0.034	-9999	-0.13	28	28
NF kappa B1 p50/RelA/I kappa B alpha	0.008	0.11	-9999	-0.27	60	60
SUMO1	0.017	0.027	-9999	-0.29	4	4
ZFPM1	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.013	0.036	-9999	-0.16	21	21
FKBP3	0.016	0.033	-9999	-0.29	6	6
Histones	0.017	0.074	-9999	-0.24	26	26
YY1/LSF	0.023	0.043	-9999	-0.23	12	12
SMG5	0.019	0.008	-9999	-0.11	2	2
RAN	0.016	0.031	-9999	-0.24	7	7
I kappa B alpha/HDAC3	0	0.094	-9999	-0.22	68	68
I kappa B alpha/HDAC1	0.002	0.1	-9999	-0.32	39	39
SAP18	0.01	0.052	-9999	-0.29	15	15
RELA	0.011	0.079	-9999	-0.18	60	60
HDAC1/Smad7	0.03	0.033	-9999	-0.16	11	11
RANGAP1	0.017	0.015	-9999	-0.11	7	7
HDAC3/TR2	0.017	0.064	-9999	-0.28	15	15
NuRD/MBD3 Complex	-0.003	0.13	-9999	-0.4	36	36
NF kappa B1 p50/RelA	0.017	0.078	-9999	-0.26	18	18
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	0.018	0.011	-9999	-10000	0	0
GATA1	0.019	0	-9999	-10000	0	0
Mad/Max	0.028	0.006	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.002	0.13	-9999	-0.39	36	36
RBBP7	0.015	0.034	-9999	-0.25	8	8
NPC	0.006	0.027	-9999	-0.14	18	18
RBBP4	-0.005	0.079	-9999	-0.24	50	50
MAX	0.019	0.006	-9999	-0.11	1	1
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.011	0.047	-9999	-0.26	14	14
NFKBIA	-0.007	0.1	-9999	-0.37	33	33
KAT2B	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.004	0.097	-9999	-0.38	22	22
SIN3 complex	0.029	0.038	-9999	-0.16	19	19
SMURF1	0.019	0	-9999	-10000	0	0
CHD3	0.019	0.006	-9999	-0.11	1	1
SAP30	0.017	0.027	-9999	-0.29	4	4
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.009	0.054	-9999	-0.27	18	18
YY1/HDAC3	0.016	0.072	-9999	-0.35	13	13
YY1/HDAC2	0.021	0.041	-9999	-0.22	11	11
YY1/HDAC1	0.023	0.041	-9999	-0.22	11	11
NuRD/MBD2 Complex (MeCP1)	0.003	0.11	-9999	-0.34	31	31
PPARG	0.003	0.088	-9999	-0.22	64	64
HDAC8/hEST1B	0.026	0.005	-9999	-10000	0	0
UBE2I	0.019	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.011	0.047	-9999	-0.26	14	14
TNFRSF1A	-0.01	0.091	-9999	-0.29	50	50
HDAC3/SMRT (N-CoR2)	0.017	0.064	-9999	-0.29	14	14
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.03	0.033	-9999	-0.16	11	11
CREBBP	0.019	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.001	0.12	-9999	-0.37	37	37
HDAC1	0.013	0.04	-9999	-0.22	13	13
HDAC3	0.007	0.069	-9999	-0.31	15	15
HDAC2	0.004	0.061	-9999	-0.22	33	33
YY1	0.016	0.041	-9999	-0.25	11	11
HDAC8	0	0	-9999	-10000	0	0
SMAD7	0.011	0.035	-9999	-0.29	3	3
NCOR2	0.019	0	-9999	-10000	0	0
MXD1	0.019	0.006	-9999	-10000	0	0
STAT3	0.003	0.08	-9999	-0.25	43	43
NFKB1	0.014	0.038	-9999	-0.22	12	12
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.007	0.057	-9999	-0.26	22	22
YY1/LSF/HDAC1	0.028	0.05	-9999	-0.22	12	12
YY1/SAP30/HDAC1	0.031	0.044	-9999	-0.2	11	11
EP300	0.012	0.046	-9999	-0.24	15	15
STAT3 (dimer non-phopshorylated)	0.003	0.08	-9999	-0.25	43	43
proteasomal ubiquitin-dependent protein catabolic process	-0.006	0.1	-9999	-0.36	33	33
histone deacetylation	0.003	0.1	-9999	-0.34	31	31
STAT3 (dimer non-phopshorylated)/HDAC3	0.007	0.1	-9999	-0.37	25	25
nuclear export	-0.025	0.005	-9999	-10000	0	0
PRKACA	0.019	0	-9999	-10000	0	0
GATAD2B	0	0	-9999	-10000	0	0
GATAD2A	0	0.075	-9999	-0.29	33	33
GATA2/HDAC3	0.017	0.065	-9999	-0.29	14	14
GATA1/HDAC1	0.024	0.028	-9999	-0.19	8	8
GATA1/HDAC3	0.017	0.064	-9999	-0.29	14	14
CHD4	0.007	0.059	-9999	-0.29	20	20
TNF-alpha/TNFR1A	0.007	0.065	-9999	-0.19	50	50
SIN3/HDAC complex/Mad/Max	0.012	0.088	-9999	-0.34	21	21
NuRD Complex	0.004	0.12	-9999	-0.38	37	37
positive regulation of chromatin silencing	0.015	0.072	-9999	-0.24	26	26
SIN3B	0.017	0.025	-9999	-0.29	3	3
MTA2	0.019	0.006	-9999	-0.11	1	1
SIN3A	0	0	-9999	-10000	0	0
XPO1	0.017	0.023	-9999	-0.29	3	3
SUMO1/HDAC1	0.027	0.043	-9999	-0.27	5	5
HDAC complex	0.022	0.075	-9999	-0.18	49	49
GATA1/Fog1	0.014	0	-9999	-10000	0	0
FKBP25/HDAC1/HDAC2	0.024	0.052	-9999	-0.17	29	29
TNF	0.018	0.01	-9999	-0.11	3	3
negative regulation of cell growth	0.012	0.087	-9999	-0.34	21	21
NuRD/MBD2/PRMT5 Complex	0.003	0.11	-9999	-0.34	31	31
Ran/GTP/Exportin 1	0.03	0.046	-9999	-0.16	21	21
NF kappa B/RelA/I kappa B alpha	0.002	0.11	-9999	-0.28	59	59
SIN3/HDAC complex/NCoR1	0.002	0.11	-9999	-0.39	24	24
TFCP2	0.012	0.043	-9999	-0.25	13	13
NR2C1	0.019	0	-9999	-10000	0	0
MBD3	0.008	0.056	-9999	-0.29	18	18
MBD2	0.019	0	-9999	-10000	0	0

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	0.023	0	-9999	-10000	0	0
RGS9BP	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0	0	-9999	-10000	0	0
mol:Na +	-0.024	0.07	-9999	-0.16	99	99
mol:ADP	0	0	-9999	-10000	0	0
GNAT2	0.019	0	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.023	0.016	-9999	-0.16	1	1
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0.026	0	-9999	-10000	0	0
GRK7	0	0	-9999	-10000	0	0
CNGB3	0.019	0	-9999	-10000	0	0
Cone Metarhodopsin II/X-Arrestin	0.014	0	-9999	-10000	0	0
mol:Ca2+	-0.019	0.06	-9999	-0.13	99	99
Cone PDE6	0.042	0.016	-9999	-0.12	1	1
Cone Metarhodopsin II	0	0	-9999	-10000	0	0
Na + (4 Units)	-0.011	0.066	-9999	-0.13	99	99
GNAT2/GDP	0.031	0.015	-9999	-0.12	1	1
GNB5	0.017	0.019	-9999	-0.14	7	7
mol:GMP (4 units)	0.023	0	-9999	-10000	0	0
Cone Transducin	0.025	0	-9999	-10000	0	0
SLC24A2	0.019	0.008	-9999	-0.11	2	2
GNB3/GNGT2	0.014	0	-9999	-10000	0	0
GNB3	0.019	0	-9999	-10000	0	0
GNAT2/GTP	0.014	0	-9999	-10000	0	0
CNGA3	-0.066	0.12	-9999	-0.29	99	99
ARR3	0.019	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.024	0.07	-9999	-0.16	99	99
mol:Pi	0.022	0.016	-9999	-0.16	1	1
Cone CNG Channel	0.003	0.062	-9999	-0.11	99	99
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	0.019	0.008	-9999	-0.11	2	2
RGS9	0.016	0.02	-9999	-0.11	13	13
PDE6C	0.019	0	-9999	-10000	0	0
GNGT2	0	0	-9999	-10000	0	0
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.019	0	-9999	-10000	0	0

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.013	0.037	-9999	-10000	0	0
TP53	-0.021	0.065	-9999	-0.27	31	31
Senescence	-0.021	0.065	-9999	-0.27	31	31
Apoptosis	-0.021	0.065	-9999	-0.27	31	31
Activated_Oncogenes	0	0	-9999	-10000	0	0
MDM2	0.011	0.025	-9999	-10000	0	0
MDM4	0.013	0.027	-9999	-0.11	23	23

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.027	0.015	-9999	-0.19	2	2
FBXW11	0.011	0.047	-9999	-0.26	14	14
NF kappa B1 p50/c-Rel	0.027	0.022	-9999	-0.15	7	7
NF kappa B1 p50/RelA/I kappa B alpha	0.026	0.063	-9999	-0.27	13	13
NFKBIA	0.006	0.062	-9999	-0.19	41	41
MAPK14	0.018	0.013	-9999	-0.11	5	5
NF kappa B1 p105/p50	0.022	0.036	-9999	-0.16	18	18
ARRB2	0.013	0.029	-9999	-0.23	7	7
REL	0.019	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.026	0.022	-9999	-0.15	7	7
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.026	0.025	-9999	-0.15	9	9
PIK3CA	-0.011	0.085	-9999	-0.22	65	65
NF kappa B1 p50 dimer	0.018	0.025	-9999	-0.19	7	7
PIK3R1	-0.015	0.095	-9999	-0.27	62	62
NFKB1	0.017	0.025	-9999	-0.19	7	7
RELA	0.018	0.02	-9999	-0.23	3	3
positive regulation of anti-apoptosis	0.019	0.039	-9999	-0.2	2	2
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.028	0.064	-9999	-0.26	15	15
SRC	0.019	0	-9999	-10000	0	0
PI3K	-0.015	0.092	-9999	-0.21	87	87
NF kappa B1 p50/RelA	0.019	0.04	-9999	-0.2	2	2
IKBKB	0.019	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.011	0.047	-9999	-0.26	14	14
SYK	-0.005	0.072	-9999	-0.18	62	62
I kappa B alpha/PIK3R1	0.009	0.076	-9999	-0.28	26	26
cell death	0.027	0.062	-9999	-0.25	15	15
NF kappa B1 p105/c-Rel	0.027	0.022	-9999	-0.15	7	7
LCK	0.017	0.016	-9999	-0.11	8	8
BCL3	0.019	0.008	-9999	-0.11	2	2

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.027	0.037	-10000	0	-0.14	21	21
HDAC3	0.018	0.013	-10000	0	-0.29	1	1
Ran/GTP/Exportin 1/HDAC4	-0.009	0.034	-10000	0	-0.12	37	37
GATA1/HDAC4	0.02	0.039	-10000	0	-0.19	16	16
GATA1/HDAC5	0.026	0.016	-10000	0	-0.19	1	1
GATA2/HDAC5	0.025	0.018	-10000	0	-0.19	1	1
HDAC5/BCL6/BCoR	0.016	0.058	-10000	0	-0.16	44	44
HDAC9	-0.017	0.094	-10000	0	-0.24	74	74
Glucocorticoid receptor/Hsp90/HDAC6	0.033	0.035	-10000	0	-0.16	16	16
HDAC4/ANKRA2	0.017	0.047	-10000	0	-0.2	21	21
HDAC5/YWHAB	0.023	0.031	-10000	0	-0.22	7	7
NPC/RanGAP1/SUMO1/Ubc9	0.013	0.036	-10000	0	-0.16	21	21
GATA2	0.018	0.011	-10000	0	-10000	0	0
HDAC4/RFXANK	0.011	0.058	-10000	0	-0.2	34	34
BCOR	0.01	0.032	-10000	0	-0.11	35	35
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0	0	-10000	0	-10000	0	0
HDAC5	0.016	0.023	-10000	0	-0.13	12	12
GNB1/GNG2	0.006	0.041	-10000	0	-0.2	21	21
Histones	0.002	0.069	-10000	0	-0.17	60	60
ADRBK1	0.018	0.014	-10000	0	-0.11	6	6
HDAC4	0.007	0.056	-10000	0	-0.22	27	27
XPO1	0.017	0.023	-10000	0	-0.29	3	3
HDAC5/ANKRA2	0.023	0.029	-10000	0	-0.19	7	7
HDAC4/Ubc9	0.02	0.039	-10000	0	-0.19	16	16
HDAC7	0	0	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.02	0.036	-10000	0	-0.19	12	12
TUBA1B	0.018	0.013	-10000	0	-0.29	1	1
HDAC6	0.019	0	-10000	0	-10000	0	0
HDAC5/RFXANK	0.017	0.045	-10000	0	-0.19	21	21
CAMK4	0.018	0.011	-10000	0	-0.11	4	4
Tubulin/HDAC6	0.024	0.051	-10000	0	-0.16	39	39
SUMO1	0.017	0.027	-10000	0	-0.29	4	4
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.015	0.035	-10000	0	-0.29	7	7
GATA1	0.019	0	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.011	0.045	-10000	0	-0.21	19	19
NR3C1	0.01	0.052	-10000	0	-0.28	16	16
SUMO1/HDAC4	0.024	0.045	-10000	0	-0.27	5	5
SRF	0.019	0	-10000	0	-10000	0	0
HDAC4/YWHAB	0.017	0.049	-10000	0	-0.21	21	21
Tubulin	0.012	0.059	-10000	0	-0.2	39	39
HDAC4/14-3-3 E	0.014	0.051	-10000	0	-0.2	26	26
GNB1	0.007	0.061	-10000	0	-0.29	21	21
RANGAP1	0.017	0.015	-10000	0	-0.11	7	7
BCL6/BCoR	0.004	0.062	-10000	0	-0.19	40	40
HDAC4/HDAC3/SMRT (N-CoR2)	0.031	0.035	-10000	0	-0.15	17	17
HDAC4/SRF	0.031	0.035	-10000	0	-0.15	16	16
HDAC4/ER alpha	0.02	0.039	-10000	0	-0.19	16	16
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.002	0.069	-10000	0	-0.17	60	60
cell motility	0.024	0.051	-10000	0	-0.15	39	39
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.019	0	-10000	0	-10000	0	0
HDAC7/HDAC3	0.014	0.009	-10000	0	-0.2	1	1
BCL6	-0.007	0.082	-10000	0	-0.29	37	37
HDAC4/CaMK II delta B	0.007	0.056	-10000	0	-0.22	27	27
Hsp90/HDAC6	0.028	0.013	-10000	0	-0.19	2	2
ESR1	0.019	0	-10000	0	-10000	0	0
HDAC6/HDAC11	0.028	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.03	0.046	-10000	0	-0.16	21	21
NPC	0.006	0.027	-10000	0	-0.14	18	18
MEF2C	0.009	0.051	-10000	0	-0.21	24	24
RAN	0.016	0.031	-10000	0	-0.24	7	7
HDAC4/MEF2C	0.044	0.044	-10000	0	-0.12	29	29
GNG2	0	0	-10000	0	-10000	0	0
NCOR2	0.019	0	-10000	0	-10000	0	0
TUBB2A	-0.004	0.081	-10000	0	-0.29	40	40
HDAC11	0.019	0	-10000	0	-10000	0	0
HSP90AA1	0.018	0.019	-10000	0	-0.29	2	2
RANBP2	0.007	0.057	-10000	0	-0.26	22	22
ANKRA2	0.015	0.034	-10000	0	-0.23	9	9
RFXANK	0.007	0.06	-10000	0	-0.28	22	22
nuclear import	-0.017	0.064	0.23	27	-10000	0	27

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.015	0.022	-10000	0	-0.11	16	16
ANTXR2	0	0	-10000	0	-10000	0	0
negative regulation of myeloid dendritic cell antigen processing and presentation	0	0.002	-10000	0	-10000	0	0
monocyte activation	-0.086	0.16	-10000	0	-0.36	139	139
MAP2K2	0.012	0.03	-10000	0	-0.68	1	1
MAP2K1	0.005	0.005	-10000	0	-0.045	4	4
MAP2K7	0.006	0.002	-10000	0	-10000	0	0
MAP2K6	0.006	0.003	-10000	0	-0.045	1	1
CYAA	0.003	0.009	-10000	0	-0.046	16	16
MAP2K4	0.005	0.007	-10000	0	-0.046	8	8
IL1B	-0.013	0.039	-10000	0	-0.16	18	18
Channel	0.01	0.011	-10000	0	-0.05	16	16
NLRP1	0.006	0.002	-10000	0	-10000	0	0
CALM1	0.007	0.056	-10000	0	-0.21	28	28
negative regulation of phagocytosis	-0.004	0.083	-10000	0	-0.47	16	16
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0	0.002	-10000	0	-10000	0	0
MAPK3	0.006	0.003	-10000	0	-0.045	1	1
MAPK1	0.005	0.007	-10000	0	-0.046	9	9
PGR	0.006	0.003	-10000	0	-0.045	1	1
PA/Cellular Receptors	0.011	0.012	-10000	0	-0.056	16	16
apoptosis	0	0.002	-10000	0	-10000	0	0
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.01	0.009	-10000	0	-0.043	16	16
macrophage activation	0.006	0.022	-10000	0	-0.12	13	13
TNF	0.018	0.01	-10000	0	-0.11	3	3
VCAM1	-0.086	0.16	-10000	0	-0.36	139	139
platelet activation	-0.004	0.083	-10000	0	-0.47	16	16
MAPKKK cascade	-0.008	0.009	0.07	3	-10000	0	3
IL18	-0.008	0.034	-10000	0	-0.072	80	80
negative regulation of macrophage activation	0	0.002	-10000	0	-10000	0	0
LEF	0	0.002	-10000	0	-10000	0	0
CASP1	0.004	0.005	-10000	0	-0.08	1	1
mol:cAMP	-0.004	0.083	-10000	0	-0.47	16	16
necrosis	0	0.002	-10000	0	-10000	0	0
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.01	0.01	-10000	0	-0.046	16	16
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.012	0.089	-9999	-0.43	20	20
Crk/p130 Cas/Paxillin	-0.032	0.071	-9999	-0.24	42	42
JUN	0.022	0.058	-9999	-0.27	14	14
HRAS	0.009	0.055	-9999	-0.28	18	18
RET51/GFRalpha1/GDNF/GRB10	0.024	0.055	-9999	-0.13	45	45
RAP1A	0.018	0.019	-9999	-0.29	2	2
FRS2	0.018	0.013	-9999	-0.11	5	5
RAP1A/GDP	0.013	0.013	-9999	-0.2	2	2
RET51/GFRalpha1/GDNF/DOK1	0.047	0.015	-9999	-10000	0	0
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.015	0.033	-9999	-0.26	7	7
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.009	0.053	-9999	-0.28	17	17
RET9/GFRalpha1/GDNF/Enigma	0.037	0.005	-9999	-10000	0	0
RHOA	0.015	0.035	-9999	-0.29	7	7
RAP1A/GTP	0.043	0.016	-9999	-0.11	2	2
GRB7	0.016	0.019	-9999	-0.11	11	11
RET51/GFRalpha1/GDNF	0.047	0.015	-9999	-10000	0	0
MAPKKK cascade	0.026	0.044	-9999	-0.21	12	12
BCAR1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	0.024	0.04	-9999	-0.13	26	26
lamellipodium assembly	-0.03	0.072	-9999	-0.24	39	39
RET51/GFRalpha1/GDNF/SHC	0.037	0.034	-9999	-0.13	9	9
PIK3CA	-0.011	0.085	-9999	-0.22	65	65
RET9/GFRalpha1/GDNF/SHC	0.028	0.03	-9999	-0.13	11	11
RET9/GFRalpha1/GDNF/Shank3	0.024	0.004	-9999	-10000	0	0
MAPK3	0.031	0.013	-9999	-10000	0	0
DOK1	0.019	0	-9999	-10000	0	0
DOK6	0	0	-9999	-10000	0	0
PXN	0.018	0.011	-9999	-0.11	4	4
neurite development	0.031	0.037	-9999	-0.18	13	13
DOK5	-0.026	0.11	-9999	-0.27	82	82
GFRA1	0.019	0.008	-9999	-0.11	2	2
MAPK8	0.025	0.048	-9999	-0.25	7	7
HRAS/GTP	0.035	0.042	-9999	-0.19	9	9
tube development	0.025	0.019	-9999	-0.12	8	8
MAPK1	0.03	0.015	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	0.026	0.037	-9999	-0.23	10	10
Rac1/GDP	0.011	0.024	-9999	-0.2	7	7
SRC	0.019	0	-9999	-10000	0	0
PDLIM7	0.019	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	0.043	0.014	-9999	-10000	0	0
SHC1	0.004	0.052	-9999	-0.14	48	48
RET51/GFRalpha1/GDNF/Dok4	0.047	0.015	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok5	0.02	0.063	-9999	-0.13	73	73
PRKCA	0.019	0	-9999	-10000	0	0
HRAS/GDP	0.007	0.037	-9999	-0.2	17	17
CREB1	0.02	0.049	-9999	-0.22	17	17
PIK3R1	-0.015	0.095	-9999	-0.27	62	62
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	0.014	0.046	-9999	-0.16	28	28
RET51/GFRalpha1/GDNF/Grb7	0.045	0.019	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
RET	0.015	0.022	-9999	-0.11	15	15
DOK4	0.019	0	-9999	-10000	0	0
JNK cascade	0.022	0.058	-9999	-0.26	14	14
RET9/GFRalpha1/GDNF/FRS2	0.036	0.009	-9999	-10000	0	0
SHANK3	0	0	-9999	-10000	0	0
RASA1	0.003	0.069	-9999	-0.28	29	29
NCK1	0.014	0.036	-9999	-0.19	14	14
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	0.016	0.037	-9999	-0.18	16	16
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	0.031	0.038	-9999	-0.32	4	4
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	0.024	0.051	-9999	-0.18	29	29
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	0.02	0.038	-9999	-0.17	16	16
PI3K	-0.002	0.11	-9999	-0.35	32	32
SOS1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	0.031	0.02	-9999	-0.12	8	8
GRB10	-0.018	0.091	-9999	-0.2	89	89
activation of MAPKK activity	0.029	0.043	-9999	-0.29	8	8
RET51/GFRalpha1/GDNF/FRS2	0.046	0.017	-9999	-10000	0	0
GAB1	0.003	0.056	-9999	-0.15	50	50
IRS1	-0.003	0.071	-9999	-0.19	54	54
IRS2	-0.02	0.099	-9999	-0.25	78	78
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	0.019	0.048	-9999	-0.26	3	3
RET51/GFRalpha1/GDNF/PKC alpha	0.047	0.015	-9999	-10000	0	0
GRB2	0.014	0.039	-9999	-0.26	10	10
PRKACA	0.019	0	-9999	-10000	0	0
GDNF	0.019	0	-9999	-10000	0	0
RAC1	0.015	0.035	-9999	-0.29	7	7
RET51/GFRalpha1/GDNF/IRS1	0.034	0.044	-9999	-0.13	25	25
Rac1/GTP	-0.007	0.098	-9999	-0.28	39	39
RET9/GFRalpha1/GDNF	0.026	0.005	-9999	-10000	0	0
GFRalpha1/GDNF	0.028	0.006	-9999	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.013	0.084	-9999	-0.27	23	23
BAG4	0.018	0.011	-9999	-0.11	4	4
BAD	0.014	0.033	-9999	-0.14	11	11
NFKBIA	0.002	0.066	-9999	-0.24	34	34
BIRC3	-0.001	0.048	-9999	-0.11	78	78
BAX	0.014	0.031	-9999	-0.12	9	9
EnzymeConsortium:3.1.4.12	0.007	0.019	-9999	-0.058	17	17
IKBKB	0.013	0.083	-9999	-0.31	13	13
MAP2K2	0.02	0.035	-9999	-0.14	14	14
MAP2K1	0.019	0.038	-9999	-0.14	17	17
SMPD1	0.011	0.019	-9999	-0.095	1	1
GO:0005551	0	0	-9999	-10000	0	0
FADD/Caspase 8	0.024	0.074	-9999	-0.25	12	12
MAP2K4	0.017	0.031	-9999	-0.12	9	9
protein ubiquitination	0.013	0.084	-9999	-0.32	13	13
EnzymeConsortium:2.7.1.37	0.022	0.038	-9999	-0.16	12	12
response to UV	0	0	-9999	-0.001	12	12
RAF1	0.017	0.036	-9999	-0.13	19	19
CRADD	0.017	0.015	-9999	-0.11	7	7
mol:ceramide	0.012	0.027	-9999	-0.094	11	11
I-kappa-B-alpha/RELA/p50/ubiquitin	0.015	0.041	-9999	-0.16	26	26
MADD	0.018	0.015	-9999	-0.2	2	2
MAP3K1	0.015	0.028	-9999	-0.099	9	9
TRADD	0.019	0	-9999	-10000	0	0
RELA/p50	0.018	0.02	-9999	-0.23	3	3
MAPK3	0.022	0.036	-9999	-0.15	12	12
MAPK1	0.02	0.046	-9999	-0.21	14	14
p50/RELA/I-kappa-B-alpha	0.016	0.049	-9999	-0.19	26	26
FADD	0.018	0.075	-9999	-0.2	50	50
KSR1	0.016	0.026	-9999	-0.11	5	5
MAPK8	0.02	0.029	-9999	-0.12	6	6
TRAF2	0.019	0	-9999	-10000	0	0
response to radiation	0	0	-9999	-0.001	5	5
CHUK	0.012	0.083	-9999	-0.32	13	13
TNF R/SODD	0.007	0.065	-9999	-0.19	50	50
TNF	0.018	0.01	-9999	-0.11	3	3
CYCS	0.013	0.031	-9999	-0.12	12	12
IKBKG	0.013	0.083	-9999	-0.31	13	13
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.015	0.078	-9999	-0.22	50	50
RELA	0.018	0.02	-9999	-0.23	3	3
RIPK1	0.016	0.019	-9999	-0.11	11	11
AIFM1	0.012	0.033	-9999	-0.13	14	14
TNF/TNF R/SODD	0.02	0.057	-9999	-0.15	50	50
TNFRSF1A	-0.01	0.091	-9999	-0.29	50	50
response to heat	0	0	-9999	-0.001	5	5
CASP8	0.024	0.047	-9999	-0.63	2	2
NSMAF	0.016	0.079	-9999	-0.26	21	21
response to hydrogen peroxide	0	0	-9999	-0.001	12	12
BCL2	0.019	0	-9999	-10000	0	0

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	0.084	0.22	-10000	0	-0.72	24	24
PCK1	0.084	0.14	-10000	0	-0.66	4	4
HNF4A	0.11	0.18	-10000	0	-0.79	7	7
KCNJ11	0.1	0.2	-10000	0	-0.67	15	15
AKT1	0.069	0.13	-10000	0	-0.39	20	20
response to starvation	0.006	0.003	-10000	0	-10000	0	0
DLK1	0.1	0.21	-10000	0	-0.77	11	11
NKX2-1	0.077	0.12	-10000	0	-0.43	1	1
ACADM	0.095	0.2	-10000	0	-0.8	13	13
TAT	0.082	0.14	-10000	0	-0.65	6	6
CEBPB	0.001	0.076	-10000	0	-0.22	51	51
CEBPA	-0.021	0.1	-10000	0	-0.22	103	103
TTR	0.04	0.18	-10000	0	-0.67	11	11
PKLR	0.099	0.18	-10000	0	-0.71	11	11
APOA1	0.12	0.22	-10000	0	-0.92	8	8
CPT1C	0.091	0.18	-10000	0	-0.71	11	11
ALAS1	0.058	0.26	-10000	0	-1.4	15	15
TFRC	0.042	0.33	-10000	0	-1	40	40
FOXF1	-0.002	0.041	-10000	0	-0.12	55	55
NF1	0.022	0.028	-10000	0	-0.14	13	13
HNF1A (dimer)	0.038	0.003	-10000	0	-10000	0	0
CPT1A	0.099	0.18	-10000	0	-0.71	11	11
HMGCS1	0.095	0.18	-10000	0	-0.71	12	12
NR3C1	0.021	0.054	-10000	0	-0.28	15	15
CPT1B	0.099	0.18	-10000	0	-0.71	11	11
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.026	0	-10000	0	-10000	0	0
GCK	0.098	0.18	-10000	0	-0.71	11	11
CREB1	0.024	0.035	-10000	0	-0.28	6	6
IGFBP1	0.069	0.14	-10000	0	-0.57	10	10
PDX1	0.11	0.12	-10000	0	-10000	0	0
UCP2	0.049	0.28	-10000	0	-0.69	57	57
ALDOB	0.11	0.2	-10000	0	-0.76	11	11
AFP	0.023	0.033	-10000	0	-10000	0	0
BDH1	0.085	0.21	-10000	0	-0.71	23	23
HADH	0.11	0.22	-10000	0	-0.85	15	15
F2	0.12	0.22	-10000	0	-0.92	8	8
HNF1A	0.038	0.003	-10000	0	-10000	0	0
G6PC	0.02	0.091	-10000	0	-10000	0	0
SLC2A2	0.11	0.14	-10000	0	-0.51	1	1
INS	0.012	0.029	0.18	10	-10000	0	10
FOXA1	0.013	0.011	-10000	0	-10000	0	0
FOXA3	0.026	0.058	-10000	0	-0.2	26	26
FOXA2	0.15	0.24	-10000	0	-0.87	11	11
ABCC8	0.11	0.2	-10000	0	-0.76	11	11
ALB	0.024	0.03	-10000	0	-10000	0	0

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.011	0.043	-9999	-0.18	21	21
alphaV beta3 Integrin	0.016	0.048	-9999	-0.19	25	25
PTK2	0.014	0.087	-9999	-0.36	21	21
positive regulation of JNK cascade	-0.003	0.034	-9999	-0.28	5	5
CDC42/GDP	0.044	0.057	-9999	-0.38	5	5
Rac1/GDP	0.045	0.062	-9999	-0.34	8	8
RAP1B	0	0	-9999	-10000	0	0
RAP1A	0.018	0.019	-9999	-0.29	2	2
CTNNB1	0.017	0.023	-9999	-0.29	3	3
CDC42/GTP	0.035	0.05	-9999	-0.35	5	5
nectin-3/I-afadin	0.018	0.033	-9999	-0.19	5	5
RAPGEF1	0.03	0.063	-9999	-0.37	7	7
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.028	0.068	-9999	-0.39	9	9
PDGFB-D/PDGFRB	0.011	0.043	-9999	-0.18	21	21
TLN1	0	0.065	-9999	-0.22	33	33
Rap1/GTP	-0.007	0.038	-9999	-0.27	7	7
IQGAP1	-0.008	0.086	-9999	-0.27	49	49
Rap1/GTP/I-afadin	0.024	0.01	-9999	-0.14	2	2
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.018	0.033	-9999	-0.19	5	5
PVR	0.019	0.008	-9999	-10000	0	0
Necl-5(dimer)	0.019	0.008	-9999	-10000	0	0
mol:GDP	0.039	0.066	-9999	-0.47	5	5
MLLT4	0.019	0	-9999	-10000	0	0
PIK3CA	-0.011	0.085	-9999	-0.22	65	65
PI3K	0.01	0.085	-9999	-0.16	88	88
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.028	0	-9999	-10000	0	0
positive regulation of lamellipodium assembly	-0.004	0.039	-9999	-0.27	8	8
PVRL1	0.019	0	-9999	-10000	0	0
PVRL3	0.005	0.047	-9999	-0.13	51	51
PVRL2	0.016	0.026	-9999	-0.19	7	7
PIK3R1	-0.015	0.095	-9999	-0.27	62	62
CDH1	0.012	0.029	-9999	-0.11	28	28
CLDN1	0.016	0.019	-9999	-0.11	11	11
JAM-A/CLDN1	0.031	0.044	-9999	-0.14	15	15
SRC	0.029	0.067	-9999	-0.53	5	5
ITGB3	0.019	0.008	-9999	-0.11	2	2
nectin-1(dimer)/I-afadin/I-afadin	0.028	0	-9999	-10000	0	0
FARP2	0.037	0.062	-9999	-0.46	5	5
RAC1	0.015	0.035	-9999	-0.29	7	7
CTNNA1	0.011	0.048	-9999	-0.29	13	13
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.03	0.03	-9999	-0.14	7	7
nectin-1/I-afadin	0.028	0	-9999	-10000	0	0
nectin-2/I-afadin	0.026	0.018	-9999	-0.19	3	3
RAC1/GTP/IQGAP1/filamentous actin	0.008	0.055	-9999	-0.16	50	50
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.03	0.029	-9999	-0.15	5	5
CDC42/GTP/IQGAP1/filamentous actin	0.009	0.052	-9999	-0.16	44	44
F11R	0.005	0.049	-9999	-0.14	48	48
positive regulation of filopodium formation	-0.003	0.034	-9999	-0.28	5	5
alphaV/beta3 Integrin/Talin	0.008	0.078	-9999	-0.24	32	32
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.026	0.018	-9999	-0.19	3	3
nectin-2(dimer)/I-afadin/I-afadin	0.026	0.018	-9999	-0.19	3	3
PIP5K1C	0.003	0.061	-9999	-0.24	28	28
VAV2	0.038	0.063	-9999	-0.47	5	5
RAP1/GDP	0.036	0.053	-9999	-0.35	5	5
ITGAV	0.003	0.067	-9999	-0.25	32	32
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.028	0.035	-9999	-0.16	8	8
nectin-3(dimer)/I-afadin/I-afadin	0.018	0.033	-9999	-0.19	5	5
Rac1/GTP	0.037	0.056	-9999	-0.33	8	8
PTPRM	0.001	0.061	-9999	-0.26	25	25
E-cadherin/beta catenin/alpha catenin	0.046	0.037	-9999	-0.17	4	4
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.017	0.016	-9999	-0.11	8	8

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	0.029	0.06	-9999	-0.24	13	13
FYN	0.003	0.1	-9999	-0.29	36	36
LAT/GRAP2/SLP76	0.031	0.073	-9999	-0.26	15	15
IKBKB	0.019	0	-9999	-10000	0	0
AKT1	0.028	0.069	-9999	-0.22	22	22
B2M	0.018	0.027	-9999	-0.29	4	4
IKBKG	0.021	0.027	-9999	-0.081	15	15
MAP3K8	0.004	0.042	-9999	-0.11	62	62
mol:Ca2+	-0.001	0.004	-9999	-0.026	6	6
integrin-mediated signaling pathway	0.012	0.011	-9999	-0.16	2	2
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.029	0.085	-9999	-0.29	20	20
TRPV6	0.003	0.004	-9999	-10000	0	0
CD28	0.019	0.001	-9999	-10000	0	0
SHC1	0.028	0.062	-9999	-0.29	10	10
receptor internalization	0.034	0.042	-9999	-0.19	2	2
PRF1	0.031	0.047	-9999	-10000	0	0
KRAS	0.011	0.048	-9999	-0.28	14	14
GRB2	0.014	0.039	-9999	-0.26	10	10
COT/AKT1	0.029	0.063	-9999	-0.18	21	21
LAT	0.032	0.058	-9999	-0.27	9	9
EntrezGene:6955	0.001	0.002	-9999	-10000	0	0
CD3D	0.01	0.035	-9999	-0.11	40	40
CD3E	0.019	0.009	-9999	-10000	0	0
CD3G	0.017	0.019	-9999	-0.11	11	11
RASGRP2	0.011	0.01	-9999	-10000	0	0
RASGRP1	-0.013	0.12	-9999	-0.23	101	101
HLA-A	0.013	0.047	-9999	-0.3	12	12
RASSF5	0	0	-9999	-10000	0	0
RAP1A/GTP/RAPL	0.012	0.011	-9999	-0.16	2	2
mol:GTP	0	0	-9999	-10000	0	0
mol:GDP	0.008	0.042	-9999	-0.095	35	35
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.009	0.028	-9999	-0.12	23	23
PRKCA	0.026	0.041	-9999	-0.14	12	12
GRAP2	0.019	0	-9999	-10000	0	0
mol:IP3	-0.014	0.041	-9999	-0.2	15	15
EntrezGene:6957	0.001	0.002	-9999	-10000	0	0
TCR/CD3/MHC I/CD8	0.028	0.034	-9999	-10000	0	0
ORAI1	0	0	-9999	-10000	0	0
CSK	0.03	0.059	-9999	-0.28	8	8
B7 family/CD28	0.039	0.072	-9999	-0.23	16	16
CHUK	0.016	0.024	-9999	-0.15	9	9
TCR/CD3/MHC I/CD8/LCK/ZAP-70	0.03	0.061	-9999	-0.29	9	9
PTPN6	0.025	0.067	-9999	-0.25	15	15
VAV1	0.032	0.059	-9999	-0.27	8	8
Monovalent TCR/CD3	0.023	0.021	-9999	-0.14	1	1
CBL	0.019	0	-9999	-10000	0	0
LCK	0.016	0.082	-9999	-0.29	19	19
PAG1	0.028	0.057	-9999	-0.27	9	9
RAP1A	0.018	0.019	-9999	-0.29	2	2
TCR/CD3/MHC I/CD8/LCK	0.027	0.062	-9999	-0.29	9	9
CD80	0.019	0.006	-9999	-0.11	1	1
CD86	-0.003	0.074	-9999	-0.21	53	53
PDK1/CARD11/BCL10/MALT1	-0.011	0.034	-9999	-0.14	24	24
HRAS	0.009	0.055	-9999	-0.28	18	18
GO:0035030	0.025	0.062	-9999	-0.21	16	16
CD8A	0.001	0.002	-9999	-10000	0	0
CD8B	0.019	0.012	-9999	-0.11	4	4
PTPRC	-0.031	0.11	-9999	-0.23	108	108
PDK1/PKC theta	0.035	0.075	-9999	-0.27	15	15
CSK/PAG1	0.029	0.058	-9999	-0.27	8	8
SOS1	0	0	-9999	-10000	0	0
peptide-MHC class I	0.023	0.039	-9999	-0.19	16	16
GRAP2/SLP76	0.031	0.079	-9999	-0.33	11	11
STIM1	0.003	0.004	-9999	-10000	0	0
RAS family/GTP	0.006	0.066	-9999	-0.16	42	42
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	0.035	0.043	-9999	-0.2	2	2
mol:DAG	-0.013	0.037	-9999	-0.18	16	16
RAP1A/GDP	0.006	0.021	-9999	-0.048	27	27
PLCG1	0.017	0.025	-9999	-0.22	5	5
CD247	0.018	0.015	-9999	-0.11	7	7
cytotoxic T cell degranulation	0.031	0.047	-9999	-10000	0	0
RAP1A/GTP	0	0.004	-9999	-0.052	2	2
mol:PI-3-4-5-P3	0.029	0.076	-9999	-0.26	20	20
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.015	0.049	-9999	-0.24	15	15
NRAS	-0.01	0.086	-9999	-0.29	42	42
ZAP70	0.019	0.006	-9999	-0.11	1	1
GRB2/SOS1	0.011	0.026	-9999	-0.17	10	10
LAT/GRAP2/SLP76/VAV1	0.028	0.068	-9999	-0.24	16	16
MALT1	0.013	0.036	-9999	-0.16	18	18
TRAF6	0.018	0.019	-9999	-0.29	2	2
CD8 heterodimer	0.015	0.009	-9999	-0.072	4	4
CARD11	0	0	-9999	-10000	0	0
PRKCB	-0.01	0.028	-9999	-0.14	16	16
PRKCE	0.026	0.041	-9999	-0.14	12	12
PRKCQ	0.032	0.08	-9999	-0.3	15	15
LCP2	-0.012	0.085	-9999	-0.21	70	70
BCL10	0.016	0.028	-9999	-0.23	6	6
regulation of survival gene product expression	0.027	0.063	-9999	-0.19	22	22
IKK complex	0.03	0.025	-9999	-0.064	6	6
RAS family/GDP	-0.007	0.014	-9999	-0.042	57	57
MAP3K14	0.027	0.051	-9999	-0.15	16	16
PDPK1	0.031	0.066	-9999	-0.21	20	20
TCR/CD3/MHC I/CD8/Fyn	0.029	0.05	-9999	-0.28	3	3

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	0.019	0	-10000	0	-10000	0	0
CLTC	0.014	0.052	-10000	0	-0.45	3	3
calcium ion-dependent exocytosis	0.006	0.064	-10000	0	-0.19	43	43
Dynamin 2/GTP	0.02	0.007	-10000	0	-0.14	1	1
EXOC4	0	0	-10000	0	-10000	0	0
CD59	0.009	0.056	-10000	0	-0.37	5	5
CPE	0.014	0.016	-10000	0	-0.073	12	12
CTNNB1	0.017	0.023	-10000	0	-0.29	3	3
membrane fusion	0.006	0.062	-10000	0	-0.18	43	43
CTNND1	0.02	0.013	-10000	0	-0.26	1	1
DNM2	0.019	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.009	0.06	-10000	0	-0.24	21	21
TSHR	0.016	0.014	-10000	0	-0.056	18	18
INS	0.015	0.018	-10000	0	-10000	0	0
BIN1	-0.016	0.092	-10000	0	-0.23	74	74
mol:Choline	0.006	0.062	-10000	0	-0.18	43	43
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.007	0.008	-10000	0	-0.16	1	1
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.018	0.015	-10000	0	-0.2	2	2
mol:Ca2+	0.019	0.007	-10000	0	-0.14	1	1
JUP	0.011	0.043	-10000	0	-0.76	1	1
ASAP2/amphiphysin II	0.006	0.05	-10000	0	-0.14	49	49
ARF6/GTP	0.014	0.01	-10000	0	-0.13	2	2
CDH1	0.013	0.043	-10000	0	-0.76	1	1
clathrin-independent pinocytosis	0.014	0.01	-10000	0	-0.13	2	2
MAPK8IP3	0.019	0	-10000	0	-10000	0	0
positive regulation of endocytosis	0.014	0.01	-10000	0	-0.13	2	2
EXOC2	0.015	0.022	-10000	0	-0.11	16	16
substrate adhesion-dependent cell spreading	0.011	0.052	-10000	0	-0.15	38	38
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.001	0.07	-10000	0	-0.26	33	33
regulation of calcium-dependent cell-cell adhesion	-0.028	0.042	0.47	2	-10000	0	2
positive regulation of phagocytosis	0.016	0.018	-10000	0	-0.19	3	3
ARF6/GTP/JIP3	0.025	0.009	-10000	0	-0.16	1	1
ACAP1	0.005	0.059	-10000	0	-0.17	43	43
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.014	0.041	-10000	0	-0.76	1	1
clathrin heavy chain/ACAP1	0.012	0.064	-10000	0	-0.26	14	14
JIP4/KLC1	0.016	0.069	-10000	0	-0.2	43	43
EXOC1	0.008	0.051	-10000	0	-0.2	25	25
exocyst	0.011	0.052	-10000	0	-0.16	38	38
RALA/GTP	0.005	0.043	-10000	0	-0.18	26	26
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.015	0.044	-10000	0	-0.16	28	28
receptor recycling	0.014	0.01	-10000	0	-0.13	2	2
CTNNA1	0.02	0.013	-10000	0	-0.26	1	1
NME1	0.007	0.008	-10000	0	-0.16	1	1
clathrin coat assembly	0.014	0.051	-10000	0	-0.44	3	3
IL2RA	0.013	0.042	-10000	0	-0.76	1	1
VAMP3	0.016	0.018	-10000	0	-0.19	3	3
GLUT4/clathrin heavy chain/ACAP1	0.018	0.06	-10000	0	-0.24	14	14
EXOC6	0	0	-10000	0	-10000	0	0
PLD1	0.006	0.056	-10000	0	-0.22	22	22
PLD2	0.006	0.055	-10000	0	-0.22	22	22
EXOC5	-0.006	0.073	-10000	0	-0.18	65	65
PIP5K1C	0.009	0.061	-10000	0	-0.24	21	21
SDC1	0.01	0.043	-10000	0	-0.76	1	1
ARF6/GDP	0.014	0.008	-10000	0	-0.11	2	2
EXOC7	0.018	0.013	-10000	0	-0.29	1	1
E-cadherin/beta catenin	0.03	0.044	-10000	0	-0.49	2	2
mol:Phosphatidic acid	0.006	0.062	-10000	0	-0.18	43	43
endocytosis	-0.005	0.05	0.14	49	-10000	0	49
SCAMP2	0.006	0.062	-10000	0	-0.29	22	22
ADRB2	0.015	0.05	-10000	0	-0.43	3	3
EXOC3	0.017	0.021	-10000	0	-0.2	4	4
ASAP2	0	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.019	0.007	-10000	0	-0.14	1	1
KLC1	-0.002	0.077	-10000	0	-0.28	37	37
AVPR2	0.018	0.048	-10000	0	-0.41	3	3
RALA	0.005	0.063	-10000	0	-0.26	26	26
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.025	0.07	-10000	0	-0.25	22	22

×

Caspase cascade in apoptosis

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
TOP1	0.02	0.064	0.16	1	-0.25	21	22
ACTA1	0.016	0.04	0.2	1	-0.17	10	11
NUMA1	0.026	0.044	0.16	1	-0.23	7	8
SPTAN1	0.01	0.053	0.2	1	-0.18	16	17
LIMK1	0.02	0.037	0.2	1	-0.16	7	8
BIRC3	-0.001	0.048	-10000	0	-0.11	78	78
BIRC2	0.016	0.03	-10000	0	-0.29	5	5
BAX	0.014	0.035	-10000	0	-0.29	5	5
CASP10	0.013	0.025	-10000	0	-0.053	62	62
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	0.019	0.064	0.16	1	-0.25	21	22
DIABLO	0.016	0.027	-10000	0	-0.26	5	5
apoptotic nuclear changes	0.01	0.053	0.2	1	-0.17	16	17
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.017	0.015	-10000	0	-0.11	7	7
GSN	0.011	0.047	0.2	1	-0.18	13	14
MADD	0.018	0.015	-10000	0	-0.2	2	2
TFAP2A	0.029	0.021	-10000	0	-10000	0	0
BID	0.002	0.049	-10000	0	-0.2	26	26
MAP3K1	0.016	0.018	-10000	0	-10000	0	0
TRADD	0.019	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.025	0.02	-10000	0	-0.19	2	2
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	0.009	0.05	0.2	1	-0.21	9	10
CASP9	0.014	0.029	-10000	0	-0.13	18	18
DNA repair	-0.009	0.043	0.28	8	-0.17	1	9
neuron apoptosis	0.013	0.097	-10000	0	-0.67	10	10
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.026	0.042	0.2	1	-0.22	5	6
APAF1	0.019	0	-10000	0	-10000	0	0
CASP6	0.022	0.1	-10000	0	-0.88	6	6
TRAF2	0.019	0	-10000	0	-10000	0	0
ICAD/CAD	0.022	0.04	0.2	1	-0.18	5	6
CASP7	-0.005	0.067	0.21	1	-0.36	16	17
KRT18	0.015	0.025	-10000	0	-10000	0	0
apoptosis	0.015	0.069	0.21	1	-0.27	16	17
DFFA	0.018	0.041	0.2	1	-0.19	6	7
DFFB	0.02	0.037	0.2	1	-0.16	6	7
PARP1	0.009	0.044	0.17	1	-0.28	8	9
actin filament polymerization	-0.019	0.035	0.15	8	-0.19	1	9
TNF	0.018	0.01	-10000	0	-0.11	3	3
CYCS	0.01	0.03	-10000	0	-0.26	4	4
SATB1	0.005	0.11	-10000	0	-0.84	6	6
SLK	0.016	0.043	0.2	1	-0.17	9	10
p15 BID/BAX	0.011	0.046	-10000	0	-0.17	26	26
CASP2	0.025	0.046	-10000	0	-0.22	2	2
JNK cascade	-0.016	0.018	-10000	0	-10000	0	0
CASP3	0.016	0.04	0.21	1	-0.16	10	11
LMNB2	0.028	0.07	-10000	0	-0.38	9	9
RIPK1	0.016	0.019	-10000	0	-0.11	11	11
CASP4	-0.026	0.1	-10000	0	-0.23	97	97
Mammalian IAPs/DIABLO	0.023	0.038	-10000	0	-0.2	7	7
negative regulation of DNA binding	0.029	0.021	-10000	0	-10000	0	0
stress fiber formation	0.016	0.043	0.2	1	-0.17	9	10
GZMB	0.01	0.032	-10000	0	-0.14	9	9
CASP1	-0.056	0.15	-10000	0	-0.34	98	98
LMNB1	0.009	0.1	-10000	0	-0.28	45	45
APP	0.013	0.098	-10000	0	-0.68	10	10
TNFRSF1A	-0.01	0.091	-10000	0	-0.29	50	50
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.008	0.013	-10000	0	-0.07	15	15
VIM	0.015	0.068	0.21	1	-0.29	14	15
LMNA	0.031	0.054	-10000	0	-0.33	7	7
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.023	0.049	-10000	0	-0.24	2	2
LRDD	0.018	0.01	-10000	0	-0.11	3	3
SREBF1	0.015	0.041	0.2	1	-0.16	7	8
APAF-1/Caspase 9	0.002	0.049	-10000	0	-0.69	2	2
nuclear fragmentation during apoptosis	0.025	0.043	0.16	1	-0.23	7	8
CFL2	0.019	0.036	0.19	1	-0.15	7	8
GAS2	0.013	0.04	0.2	1	-0.16	9	10
positive regulation of apoptosis	0.023	0.078	-10000	0	-0.35	12	12
PRF1	0.008	0.036	-10000	0	-0.11	44	44

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.015	0.023	-10000	0	-0.11	17	17
NFATC1	0.012	0.12	-10000	0	-0.44	25	25
NFATC2	0.013	0.054	-10000	0	-0.25	12	12
NFATC3	0.01	0.025	-10000	0	-0.12	16	16
YWHAE	0.011	0.045	-10000	0	-0.21	19	19
Calcineurin A alpha-beta B1/CABIN1	0.026	0.029	-10000	0	-0.17	1	1
Exportin 1/Ran/NUP214	0.036	0.027	-10000	0	-0.2	6	6
mol:DAG	0	0	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	0.043	0.038	-10000	0	-0.17	1	1
BCL2/BAX	0.025	0.024	-10000	0	-0.19	5	5
CaM/Ca2+/Calcineurin A alpha-beta B1	0.007	0.038	-10000	0	-0.2	16	16
CaM/Ca2+	0.007	0.038	-10000	0	-0.2	16	16
BAX	0.014	0.035	-10000	0	-0.29	5	5
MAPK14	0.018	0.013	-10000	0	-0.11	5	5
BAD	0.014	0.036	-10000	0	-0.25	9	9
CABIN1/MEF2D	0.035	0.029	-10000	0	-0.15	1	1
Calcineurin A alpha-beta B1/BCL2	0.019	0	-10000	0	-10000	0	0
FKBP8	0.018	0.014	-10000	0	-0.11	6	6
activation-induced cell death of T cells	-0.035	0.029	0.15	1	-10000	0	1
KPNB1	0.007	0.059	-10000	0	-0.28	21	21
KPNA2	-0.001	0.074	-10000	0	-0.26	37	37
XPO1	0.017	0.023	-10000	0	-0.29	3	3
SFN	0.002	0.044	-10000	0	-0.11	70	70
MAP3K8	0.004	0.042	-10000	0	-0.11	62	62
NFAT4/CK1 alpha	0.022	0.046	-10000	0	-0.19	19	19
MEF2D/NFAT1/Cbp/p300	0.05	0.063	-10000	0	-0.26	13	13
CABIN1	0.026	0.03	-10000	0	-0.17	1	1
CALM1	0.007	0.056	-10000	0	-0.29	16	16
RAN	0.016	0.031	-10000	0	-0.24	7	7
MAP3K1	0.015	0.022	-10000	0	-0.11	16	16
CAMK4	0.018	0.011	-10000	0	-0.11	4	4
mol:Ca2+	0.001	0	-10000	0	-10000	0	0
MAPK3	0.019	0.006	-10000	0	-10000	0	0
YWHAH	-0.006	0.082	-10000	0	-0.25	49	49
Calcineurin A alpha-beta B1/AKAP79/PKA	0.028	0.004	-10000	0	-10000	0	0
YWHAB	0.015	0.035	-10000	0	-0.29	7	7
MAPK8	0.019	0	-10000	0	-10000	0	0
MAPK9	0.016	0.028	-10000	0	-0.23	6	6
YWHAG	0	0	-10000	0	-10000	0	0
FKBP1A	0.007	0.052	-10000	0	-0.18	31	31
NFAT1-c-4/YWHAQ	0.03	0.1	-10000	0	-0.42	19	19
PRKCH	0.016	0.019	-10000	0	-0.11	12	12
CABIN1/Cbp/p300	0.024	0.032	-10000	0	-0.19	11	11
CASP3	0.009	0.053	-10000	0	-0.25	20	20
PIM1	0.017	0.017	-10000	0	-0.11	9	9
Calcineurin A alpha-beta B1/FKBP12/FK506	0.007	0.029	-10000	0	-0.16	12	12
apoptosis	0.013	0.033	-10000	0	-0.19	12	12
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.004	0.11	-10000	0	-0.41	23	23
PRKCB	0	0	-10000	0	-10000	0	0
PRKCE	0.019	0	-10000	0	-10000	0	0
JNK2/NFAT4	0.02	0.026	-10000	0	-0.12	16	16
BAD/BCL-XL	0.022	0.03	-10000	0	-0.19	7	7
PRKCD	0.012	0.029	-10000	0	-0.11	27	27
NUP214	0.019	0	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
PRKCA	0.019	0	-10000	0	-10000	0	0
PRKCG	0.019	0	-10000	0	-10000	0	0
PRKCQ	0.014	0.024	-10000	0	-0.11	19	19
FKBP38/BCL2	0.027	0.01	-10000	0	-10000	0	0
EP300	0.012	0.046	-10000	0	-0.24	15	15
PRKCB1	-0.003	0.057	-10000	0	-0.13	77	77
CSNK2A1	0.01	0.053	-10000	0	-0.29	16	16
NFATc/JNK1	0.023	0.11	-10000	0	-0.41	25	25
CaM/Ca2+/FKBP38	0.019	0.035	-10000	0	-0.15	20	20
FKBP12/FK506	0.006	0.035	-10000	0	-0.12	31	31
CSNK1A1	0.011	0.041	-10000	0	-0.2	16	16
CaM/Ca2+/CAMK IV	0.019	0.034	-10000	0	-0.16	17	17
NFATc/ERK1	0.023	0.11	-10000	0	-0.41	25	25
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	0.041	0.04	-10000	0	-0.19	3	3
NR4A1	0.038	0.054	-10000	0	-0.25	11	11
GSK3B	0.004	0.066	-10000	0	-0.26	29	29
positive T cell selection	0.01	0.024	-10000	0	-0.12	16	16
NFAT1/CK1 alpha	0.013	0.064	-10000	0	-0.27	18	18
RCH1/ KPNB1	0.006	0.068	-10000	0	-0.2	49	49
YWHAQ	0.018	0.019	-10000	0	-0.29	2	2
PRKACA	0.019	0	-10000	0	-10000	0	0
AKAP5	0.019	0.006	-10000	0	-0.11	1	1
MEF2D	0.02	0	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.014	0.037	-10000	0	-0.29	7	7
NFATc/p38 alpha	0.023	0.11	-10000	0	-0.41	25	25
CREBBP	0.02	0	-10000	0	-10000	0	0
BCL2	0.019	0	-10000	0	-10000	0	0

×

IL27-mediated signaling events

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.015	0.049	-10000	0	-0.28	9	9
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	-0.009	0.076	0.4	12	-10000	0	12
IL27/IL27R/JAK1	0.022	0.065	-10000	0	-10000	0	0
TBX21	0.016	0.066	-10000	0	-0.33	9	9
IL12B	0.02	0	-10000	0	-10000	0	0
IL12A	0.011	0	-10000	0	-10000	0	0
IL6ST	0	0.074	-10000	0	-0.27	35	35
IL27RA/JAK1	0.018	0.029	-10000	0	-10000	0	0
IL27	0	0.002	-10000	0	-10000	0	0
TYK2	0.008	0.061	-10000	0	-0.29	21	21
T-helper cell lineage commitment	0.018	0.038	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.009	0.076	0.4	12	-10000	0	12
T cell proliferation during immune response	-0.009	0.076	0.4	12	-10000	0	12
MAPKKK cascade	0.009	0.076	-10000	0	-0.4	12	12
STAT3	-0.003	0.079	-10000	0	-0.29	37	37
STAT2	0.019	0	-10000	0	-10000	0	0
STAT1	0.008	0.04	-10000	0	-0.12	40	40
IL12RB1	0.019	0.006	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	0.017	0.066	-10000	0	-0.33	9	9
IL27/IL27R/JAK2/TYK2	0.009	0.076	-10000	0	-0.41	12	12
positive regulation of T cell mediated cytotoxicity	0.009	0.076	-10000	0	-0.4	12	12
STAT1 (dimer)	0.022	0.083	-10000	0	-0.42	9	9
JAK2	0.013	0.027	-10000	0	-0.11	23	23
JAK1	0.001	0.07	-10000	0	-0.26	34	34
STAT2 (dimer)	0.019	0.074	-10000	0	-0.38	12	12
T cell proliferation	0.006	0.076	-10000	0	-0.4	12	12
IL12/IL12R/TYK2/JAK2	0.015	0.17	-10000	0	-0.83	20	20
IL17A	0.018	0.039	-10000	0	-10000	0	0
mast cell activation	-0.009	0.076	0.4	12	-10000	0	12
IFNG	0.007	0.019	-10000	0	-0.096	12	12
T cell differentiation	0	0.003	-10000	0	-0.018	12	12
STAT3 (dimer)	0.014	0.091	-10000	0	-0.47	12	12
STAT5A (dimer)	0.019	0.074	-10000	0	-0.38	12	12
STAT4 (dimer)	0.016	0.077	-10000	0	-0.4	12	12
STAT4	0.012	0.03	-10000	0	-0.11	30	30
T cell activation	-0.008	0.004	-10000	0	-10000	0	0
IL27R/JAK2/TYK2	0.026	0.065	-10000	0	-10000	0	0
GATA3	0.007	0.017	-10000	0	-10000	0	0
IL18	-0.002	0.036	-10000	0	-0.086	70	70
positive regulation of mast cell cytokine production	0.014	0.089	-10000	0	-0.46	12	12
IL27/EBI3	0.012	0.014	-10000	0	-10000	0	0
IL27RA	0.011	0.012	-10000	0	-10000	0	0
IL6	0.001	0.052	-10000	0	-10000	0	0
STAT5A	0.019	0.008	-10000	0	-0.11	2	2
monocyte differentiation	0	0	-10000	0	-10000	0	0
IL2	-0.005	0.006	-10000	0	-10000	0	0
IL1B	-0.009	0.046	-10000	0	-0.092	102	102
EBI3	0.015	0.022	-10000	0	-0.11	15	15
TNF	0.01	0.006	-10000	0	-0.07	3	3

×

Sumoylation by RanBP2 regulates transcriptional repression

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
HDAC1	0.013	0.04	-9999	-0.22	13	13
Ran/GTP/Exportin 1/HDAC4	-0.01	0.038	-9999	-0.16	21	21
MDM2/SUMO1	0.026	0.038	-9999	-0.25	4	4
HDAC4	0.007	0.056	-9999	-0.22	27	27
Ran/GTP/Exportin 1/HDAC1	-0.008	0.038	-9999	-0.17	19	19
SUMO1	0.017	0.027	-9999	-0.29	4	4
NPC/RanGAP1/SUMO1	0.009	0.037	-9999	-0.16	21	21
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.016	0.04	-9999	-0.16	21	21
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.016	0.031	-9999	-0.24	7	7
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.007	0.057	-9999	-0.26	22	22
SUMO1/HDAC4	0.024	0.045	-9999	-0.27	5	5
SUMO1/HDAC1	0.027	0.043	-9999	-0.27	5	5
RANGAP1	0.017	0.015	-9999	-0.11	7	7
MDM2/SUMO1/SUMO1	0.036	0.042	-9999	-0.14	21	21
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.013	0.036	-9999	-0.16	21	21
Ran/GTP	0.021	0.04	-9999	-0.15	21	21
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.011	0.032	-9999	-0.11	34	34
UBE2I	0.019	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.024	0.044	-9999	-0.16	21	21
NPC	0.006	0.027	-9999	-0.14	18	18
PIAS2	0.018	0.011	-9999	-0.11	4	4
PIAS1	0.008	0.056	-9999	-0.29	18	18
EntrezGene:9972	0	0	-9999	-10000	0	0

×

Regulation of Androgen receptor activity

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.007	0.026	-10000	0	-0.15	13	13
SMARCC1	0	0.14	-10000	0	-1.2	5	5
REL	0.018	0	-10000	0	-10000	0	0
HDAC7	0.03	0.064	-10000	0	-0.24	15	15
JUN	-0.001	0.077	-10000	0	-0.28	37	37
EP300	0.012	0.046	-10000	0	-0.24	15	15
KAT2B	0	0	-10000	0	-10000	0	0
KAT5	0	0	-10000	0	-10000	0	0
MAPK14	0.023	0.012	-10000	0	-0.15	1	1
FOXO1	-0.012	0.088	-10000	0	-0.23	67	67
T-DHT/AR	0.051	0.074	-10000	0	-0.25	15	15
MAP2K6	0.02	0.007	-10000	0	-0.12	1	1
BRM/BAF57	0.028	0.019	-10000	0	-0.19	3	3
MAP2K4	0.016	0.031	-10000	0	-0.17	12	12
SMARCA2	0.018	0.015	-10000	0	-0.11	7	7
PDE9A	-0.002	0.2	-10000	0	-0.92	24	24
NCOA2	0.019	0.01	-10000	0	-10000	0	0
CEBPA	-0.028	0.1	-10000	0	-0.22	103	103
EHMT2	0.019	0.006	-10000	0	-0.11	1	1
cell proliferation	0.064	0.076	0.24	3	-0.3	8	11
NR0B1	-0.004	0.049	-10000	0	-0.11	92	92
EGR1	-0.032	0.11	-10000	0	-0.29	74	74
RXRs/9cRA	0.037	0.011	-10000	0	-0.13	1	1
AR/RACK1/Src	0.048	0.033	-10000	0	-0.26	2	2
AR/GR	0.026	0.057	-10000	0	-0.2	26	26
GNB2L1	0.018	0.019	-10000	0	-0.29	2	2
PKN1	0.009	0.049	-10000	0	-0.18	28	28
RCHY1	0.013	0.044	-10000	0	-0.29	11	11
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
MAPK8	0.021	0.022	-10000	0	-0.19	4	4
T-DHT/AR/TIF2/CARM1	0.054	0.035	-10000	0	-0.22	3	3
SRC	0.03	0.017	-10000	0	-0.1	3	3
NR3C1	0.01	0.052	-10000	0	-0.28	16	16
KLK3	0.01	0.07	-10000	0	-0.41	1	1
APPBP2	0.008	0.06	-10000	0	-0.28	22	22
TRIM24	0.007	0.061	-10000	0	-0.29	20	20
T-DHT/AR/TIP60	0.025	0.03	-10000	0	-0.17	5	5
TMPRSS2	0.033	0.063	-10000	0	-0.73	2	2
RXRG	0.018	0.013	-10000	0	-0.11	5	5
mol:9cRA	0	0	-10000	0	-10000	0	0
RXRA	0.019	0.013	-10000	0	-0.29	1	1
RXRB	0.019	0	-10000	0	-10000	0	0
CARM1	0.019	0.015	-10000	0	-0.2	2	2
NR2C2	0.019	0	-10000	0	-10000	0	0
KLK2	0.057	0.031	-10000	0	-0.24	2	2
AR	0.022	0.05	-10000	0	-0.19	24	24
SENP1	0	0	-10000	0	-10000	0	0
HSP90AA1	0.018	0.019	-10000	0	-0.29	2	2
MDM2	0.009	0.032	-10000	0	-0.11	34	34
SRY	0.017	0.01	-10000	0	-0.11	3	3
GATA2	0.018	0.011	-10000	0	-10000	0	0
MYST2	0.001	0.071	-10000	0	-0.26	34	34
HOXB13	0.02	0.006	-10000	0	-0.11	1	1
T-DHT/AR/RACK1/Src	0.044	0.033	-10000	0	-0.26	2	2
positive regulation of transcription	0.018	0.011	-10000	0	-10000	0	0
DNAJA1	0.006	0.063	-10000	0	-0.28	24	24
proteasomal ubiquitin-dependent protein catabolic process	0.012	0.044	-10000	0	-0.27	11	11
NCOA1	0.017	0.037	-10000	0	-0.24	8	8
SPDEF	0.021	0.006	-10000	0	-0.11	1	1
T-DHT/AR/TIF2	0.03	0.06	-10000	0	-0.26	13	13
T-DHT/AR/Hsp90	0.037	0.034	-10000	0	-0.19	5	5
GSK3B	0.004	0.066	-10000	0	-0.26	29	29
NR2C1	0.019	0	-10000	0	-10000	0	0
mol:T-DHT	0.028	0.019	-10000	0	-0.12	3	3
SIRT1	0.008	0.048	-10000	0	-0.16	32	32
ZMIZ2	0.017	0	-10000	0	-10000	0	0
POU2F1	0.023	0.036	-10000	0	-0.21	4	4
T-DHT/AR/DAX-1	0.028	0.039	-10000	0	-0.16	7	7
CREBBP	0.019	0	-10000	0	-10000	0	0
SMARCE1	0.018	0.023	-10000	0	-0.29	3	3

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.01	0.052	-9999	-0.28	14	14
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.052	0.069	-9999	-0.26	12	12
ERC1	-0.002	0.074	-9999	-0.24	43	43
RIP2/NOD2	0.025	0.021	-9999	-0.19	2	2
NFKBIA	0.01	0.086	-9999	-0.34	27	27
BIRC2	0.016	0.03	-9999	-0.29	5	5
IKBKB	0.019	0	-9999	-10000	0	0
RIPK2	0.017	0.021	-9999	-0.18	5	5
IKBKG	0.037	0.034	-9999	-0.27	4	4
IKK complex/A20	0.049	0.055	-9999	-0.24	5	5
NEMO/A20/RIP2	0.017	0.021	-9999	-0.18	5	5
XPO1	0.017	0.023	-9999	-0.29	3	3
NEMO/ATM	0.043	0.037	-9999	-0.27	4	4
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.016	0.031	-9999	-0.24	7	7
Exportin 1/RanGTP	0.023	0.026	-9999	-0.21	6	6
IKK complex/ELKS	0.042	0.047	-9999	-0.27	5	5
BCL10/MALT1/TRAF6	0.032	0.03	-9999	-0.15	11	11
NOD2	0.016	0.02	-9999	-0.11	13	13
NFKB1	0.012	0.044	-9999	-0.23	12	12
RELA	0.016	0.026	-9999	-0.23	3	3
MALT1	0.013	0.036	-9999	-0.16	18	18
cIAP1/UbcH5C	0.025	0.031	-9999	-0.25	6	6
ATM	0.009	0.042	-9999	-0.15	31	31
TNF/TNFR1A	0.007	0.065	-9999	-0.19	50	50
TRAF6	0.018	0.019	-9999	-0.29	2	2
PRKCA	0.019	0	-9999	-10000	0	0
CHUK	0.016	0.024	-9999	-0.15	9	9
UBE2D3	0.017	0.023	-9999	-0.29	3	3
TNF	0.018	0.01	-9999	-0.11	3	3
NF kappa B1 p50/RelA	0.03	0.068	-9999	-0.2	39	39
BCL10	0.016	0.028	-9999	-0.23	6	6
proteasomal ubiquitin-dependent protein catabolic process	0.01	0.086	-9999	-0.34	27	27
beta TrCP1/SCF ubiquitin ligase complex	0.01	0.052	-9999	-0.28	14	14
TNFRSF1A	-0.01	0.091	-9999	-0.29	50	50
IKK complex	0.055	0.035	-9999	-0.27	3	3
CYLD	0.018	0.016	-9999	-0.29	1	1
IKK complex/PKC alpha	0.061	0.035	-9999	-0.26	3	3

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	0.012	0.056	-9999	-10000	0	0
MKNK1	0.003	0.068	-9999	-0.27	30	30
MAPK14	0.013	0.037	-9999	-0.13	11	11
ATF2/c-Jun	0.003	0.11	-9999	-0.43	34	34
MAPK11	0.014	0.033	-9999	-0.12	8	8
MITF	0.016	0.046	-9999	-0.22	7	7
MAPKAPK5	0.022	0.033	-9999	-10000	0	0
KRT8	0.018	0.041	-9999	-0.22	1	1
MAPKAPK3	0.016	0.023	-9999	-0.16	8	8
MAPKAPK2	0.019	0.008	-9999	-0.11	2	2
p38alpha-beta/CK2	0.019	0.046	-9999	-0.23	1	1
CEBPB	0.005	0.07	-9999	-0.23	31	31
SLC9A1	0.021	0.038	-9999	-0.28	2	2
mol:GDP	0	0	-9999	-10000	0	0
ATF2	0.019	0.051	-9999	-0.2	8	8
p38alpha-beta/MNK1	0.02	0.06	-9999	-0.18	27	27
JUN	0.002	0.11	-9999	-0.42	34	34
PPARGC1A	0.007	0.059	-9999	-0.24	18	18
USF1	0.013	0.033	-9999	-0.17	1	1
RAB5/GDP/GDI1	0.002	0.082	-9999	-0.26	39	39
NOS2	0.013	0.033	-9999	-0.17	1	1
DDIT3	0.003	0.065	-9999	-0.22	28	28
RAB5A	0.003	0.068	-9999	-0.29	27	27
HSPB1	0.009	0.051	-9999	-0.16	34	34
p38alpha-beta/HBP1	0.03	0.039	-9999	-0.17	1	1
CREB1	0.024	0.036	-9999	-0.19	2	2
RAB5/GDP	0.003	0.046	-9999	-0.2	27	27
EIF4E	0.01	0.055	-9999	-0.17	31	31
RPS6KA4	0.022	0.033	-9999	-10000	0	0
PLA2G4A	-0.001	0.061	-9999	-0.19	35	35
GDI1	0.003	0.086	-9999	-0.28	40	40
TP53	0.011	0.044	-9999	-0.22	3	3
RPS6KA5	0.018	0.037	-9999	-0.2	1	1
ESR1	0.022	0.033	-9999	-10000	0	0
HBP1	0.019	0	-9999	-10000	0	0
MEF2C	0.014	0.057	-9999	-0.27	13	13
MEF2A	0.017	0.048	-9999	-0.25	9	9
EIF4EBP1	0.02	0.041	-9999	-0.19	5	5
KRT19	0.018	0.041	-9999	-0.22	1	1
ELK4	0.022	0.033	-9999	-10000	0	0
ATF6	0.021	0.036	-9999	-0.27	1	1
ATF1	0.022	0.037	-9999	-0.19	1	1
p38alpha-beta/MAPKAPK2	0.03	0.04	-9999	-0.17	1	1
p38alpha-beta/MAPKAPK3	0.029	0.042	-9999	-0.18	3	3

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.001	0.14	-10000	0	-1.1	9	9
VDR	0.019	0.008	-10000	0	-0.11	2	2
FAM120B	0	0	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.025	0.097	-10000	0	-0.26	50	50
RXRs/LXRs/DNA/Oxysterols	0.015	0.15	-10000	0	-0.41	52	52
MED1	-0.002	0.078	-10000	0	-0.29	36	36
mol:9cRA	0	0.017	-10000	0	-0.073	5	5
RARs/THRs/DNA/Src-1	0.022	0.053	-10000	0	-0.16	41	41
RXRs/NUR77	0.05	0.04	0.16	1	-0.13	2	3
RXRs/PPAR	0.036	0.027	-10000	0	-0.18	1	1
NCOR2	0.019	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.014	0.005	-10000	0	-0.07	2	2
RARs/VDR/DNA/Vit D3	0.045	0.007	-10000	0	-10000	0	0
RARA	0.019	0	-10000	0	-10000	0	0
NCOA1	-0.006	0.083	-10000	0	-0.28	43	43
VDR/VDR/DNA	0.019	0.008	-10000	0	-0.11	2	2
RARs/RARs/DNA/9cRA	0.033	0.014	-10000	0	-10000	0	0
RARG	0.019	0	-10000	0	-10000	0	0
RPS6KB1	-0.005	0.055	-10000	0	-0.39	9	9
RARs/THRs/DNA/SMRT	0.036	0.01	-10000	0	-0.15	1	1
THRA	0.017	0.02	-10000	0	-0.13	8	8
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.014	0.005	-10000	0	-0.07	2	2
RXRs/PPAR/9cRA/PGJ2/DNA	0.04	0.058	0.29	2	-0.17	8	10
NR1H4	0.019	0.008	-10000	0	-0.11	2	2
RXRs/LXRs/DNA	0.057	0.076	-10000	0	-0.16	50	50
NR1H2	0.018	0.02	-10000	0	-0.1	3	3
NR1H3	0.014	0.038	-10000	0	-0.15	16	16
RXRs/VDR/DNA/Vit D3	0.046	0.037	-10000	0	-0.12	2	2
NR4A1	0.019	0.008	-10000	0	-0.11	2	2
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	0.016	0.061	-10000	0	-0.17	37	37
RXRG	0.018	0.021	-10000	0	-0.12	1	1
RXR alpha/CCPG	0.014	0.015	-10000	0	-0.2	1	1
RXRA	0.018	0.022	-10000	0	-0.3	1	1
RXRB	0.019	0.019	-10000	0	-10000	0	0
THRB	0.019	0	-10000	0	-10000	0	0
PPARG	0.015	0.024	-10000	0	-0.11	18	18
PPARD	0.019	0	-10000	0	-10000	0	0
TNF	0.021	0.14	-10000	0	-0.55	13	13
mol:Oxysterols	0.001	0.015	-10000	0	-0.067	2	2
cholesterol transport	0.016	0.15	-10000	0	-0.4	52	52
PPARA	0.019	0	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.019	0.008	-10000	0	-0.11	2	2
RXRs/NUR77/BCL2	0.03	0.016	-10000	0	-0.17	1	1
SREBF1	0.008	0.19	-10000	0	-0.78	19	19
RXRs/RXRs/DNA/9cRA	0.04	0.058	0.29	2	-0.17	8	10
ABCA1	-0.029	0.28	-10000	0	-0.92	47	47
RARs/THRs	0.055	0.013	-10000	0	-0.12	1	1
RXRs/FXR	0.05	0.04	-10000	0	-0.13	2	2
BCL2	0.019	0	-10000	0	-10000	0	0

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	0.043	0.041	-10000	0	-10000	0	0
IHH	0.028	0.014	-10000	0	-0.094	1	1
SHH Np/Cholesterol/GAS1	0.012	0.039	-10000	0	-0.14	24	24
LRPAP1	0.013	0.043	-10000	0	-0.28	11	11
dorsoventral neural tube patterning	-0.012	0.039	0.14	24	-10000	0	24
SMO/beta Arrestin2	0.053	0.031	-10000	0	-10000	0	0
SMO	0.047	0.027	-10000	0	-10000	0	0
AKT1	-0.012	0.15	-10000	0	-0.32	85	85
ARRB2	0.013	0.039	-10000	0	-0.2	15	15
BOC	0	0	-10000	0	-10000	0	0
ADRBK1	0.018	0.014	-10000	0	-0.11	6	6
heart looping	0.047	0.027	-10000	0	-10000	0	0
STIL	0.035	0.032	-10000	0	-0.17	3	3
DHH N/PTCH2	0.014	0	-10000	0	-10000	0	0
DHH N/PTCH1	0.031	0.029	-10000	0	-10000	0	0
PIK3CA	-0.011	0.085	-10000	0	-0.22	65	65
DHH	0	0	-10000	0	-10000	0	0
PTHLH	0.044	0.04	-10000	0	-10000	0	0
determination of left/right symmetry	0.047	0.027	-10000	0	-10000	0	0
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
skeletal system development	0.044	0.04	-10000	0	-10000	0	0
IHH N/Hhip	0.019	0.008	-10000	0	-10000	0	0
DHH N/Hhip	0	0	-10000	0	-10000	0	0
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	0.047	0.027	-10000	0	-10000	0	0
pancreas development	0	0	-10000	0	-10000	0	0
HHAT	0.018	0.014	-10000	0	-0.11	6	6
PI3K	-0.015	0.092	-10000	0	-0.21	87	87
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.008	0.072	-10000	0	-0.16	78	78
somite specification	0.047	0.027	-10000	0	-10000	0	0
SHH Np/Cholesterol/PTCH1	0.043	0.029	-10000	0	-0.16	1	1
SHH Np/Cholesterol/PTCH2	0.026	0.007	-10000	0	-10000	0	0
SHH Np/Cholesterol/Megalin	0.025	0.011	-10000	0	-10000	0	0
SHH	0.02	0.009	-10000	0	-10000	0	0
catabolic process	0.038	0.034	-10000	0	-0.16	3	3
SMO/Vitamin D3	0.051	0.029	-10000	0	-0.17	1	1
SHH Np/Cholesterol/Hhip	0.014	0.006	-10000	0	-10000	0	0
LRP2	0.017	0.018	-10000	0	-0.11	10	10
receptor-mediated endocytosis	0.05	0.031	-10000	0	-10000	0	0
SHH Np/Cholesterol/BOC	0.014	0.006	-10000	0	-10000	0	0
SHH Np/Cholesterol/CDO	0.026	0.007	-10000	0	-10000	0	0
mesenchymal cell differentiation	-0.013	0.006	-10000	0	-10000	0	0
mol:Vitamin D3	0.045	0.03	-10000	0	-0.16	1	1
IHH N/PTCH2	0.034	0.008	-10000	0	-10000	0	0
CDON	0.019	0	-10000	0	-10000	0	0
IHH N/PTCH1	0.045	0.037	-10000	0	-0.16	3	3
Megalin/LRPAP1	0.022	0.032	-10000	0	-0.19	10	10
PTCH2	0.019	0	-10000	0	-10000	0	0
SHH Np/Cholesterol	0.016	0.006	-10000	0	-10000	0	0
PTCH1	0.038	0.034	-10000	0	-0.16	3	3
HHIP	0	0	-10000	0	-10000	0	0

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.019	0.006	-9999	-0.11	1	1
Aurora C/Aurora B/INCENP	0.03	0.024	-9999	-0.1	5	5
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	0.006	0.062	-9999	-0.42	11	11
AURKB	0.011	0.034	-9999	-0.12	33	33
AURKC	0.015	0.022	-9999	-0.11	16	16

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.017	0.018	-10000	0	-0.25	2	2
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.015	0.028	-10000	0	-0.21	7	7
AP2	0.008	0.036	-10000	0	-0.17	19	19
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.019	0.039	-10000	0	-0.17	19	19
CLTB	0.018	0.013	-10000	0	-0.29	1	1
coatomer protein complex/ARF1/GTP/ER cargo protein	0.02	0.032	-10000	0	-0.2	10	10
CD4	-0.003	0.07	-10000	0	-0.19	56	56
CLTA	0.017	0.023	-10000	0	-0.29	3	3
mol:GTP	0	0.003	-10000	0	-10000	0	0
ARFGAP1	0.01	0.013	-10000	0	-0.2	2	2
mol:PI-4-5-P2	0.011	0.021	0.12	13	-10000	0	13
ARF1/GTP	0.008	0.019	-10000	0	-0.13	8	8
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.018	0.032	-10000	0	-0.19	11	11
mol:Choline	0.011	0.021	0.12	13	-10000	0	13
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.018	0.008	-10000	0	-0.11	2	2
DDEF1	0.009	0.019	0.12	10	-10000	0	10
ARF1/GDP	0.007	0.013	-10000	0	-0.18	2	2
AP2M1	0.009	0.053	-10000	0	-0.25	19	19
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	0.011	0.027	-10000	0	-0.15	13	13
Rac/GTP	0.012	0.025	-10000	0	-0.2	7	7
ARF1/GTP/GGA3/ARF-GAP1	0.028	0.02	-10000	0	-0.12	9	9
ARFIP2	0.009	0.047	-10000	0	-0.25	17	17
COPA	0.017	0.018	-10000	0	-0.15	5	5
RAC1	0.015	0.035	-10000	0	-0.29	7	7
ARF1/GTP/coatomer protein complex	0.019	0.031	-10000	0	-0.2	9	9
ARF1/GTP/ARHGAP10	0.009	0.02	-10000	0	-0.14	9	9
GGA3	0.019	0	-10000	0	-10000	0	0
ARF1/GTP/Membrin	0.016	0.018	-10000	0	-0.14	5	5
AP2A1	0	0	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.02	0.032	-10000	0	-0.18	10	10
ARF1/GDP/Membrin	0.018	0.017	-10000	0	-0.13	5	5
Arfaptin 2/Rac/GDP	0.018	0.039	-10000	0	-0.17	19	19
CYTH2	0	0.003	-10000	0	-10000	0	0
ARF1/GTP/GGA3	0.022	0.021	-10000	0	-0.16	7	7
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.011	0.024	-10000	0	-0.2	7	7
mol:Brefeldin A	0	0	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.01	0.063	-10000	0	-0.19	39	39
PLD2	0.011	0.021	0.12	13	-10000	0	13
ARF-GAP1/v-SNARE	0.01	0.013	-10000	0	-0.2	2	2
PIP5K1A	0.008	0.011	-10000	0	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0.015	0.019	-10000	0	-0.14	7	7
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.011	0.021	0.12	13	-10000	0	13
KDEL Receptor/Ligand/ARF-GAP1	0.01	0.013	-10000	0	-0.2	2	2
GOSR2	0.013	0.006	-10000	0	-10000	0	0
USO1	0.01	0.033	-10000	0	-0.32	5	5
GBF1	0.012	0.009	-10000	0	-10000	0	0
ARF1/GTP/Arfaptin 2	0.018	0.038	-10000	0	-0.16	20	20
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.007	0.053	-10000	0	-0.17	36	36

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.007	0	-9999	-10000	0	0
ADCY5	0.007	0	-9999	-10000	0	0
ADCY6	0.014	0.003	-9999	-0.051	1	1
ADCY7	0.012	0.011	-9999	-0.051	15	15
ADCY1	0.014	0	-9999	-10000	0	0
ADCY2	0.014	0.005	-9999	-0.051	3	3
ADCY3	0.007	0	-9999	-10000	0	0
ADCY8	0.007	0.021	-9999	-0.051	64	64
PRKCE	0.01	0	-9999	-10000	0	0
ADCY9	0.014	0.007	-9999	-0.051	6	6
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	0.015	0.012	-9999	-10000	0	0

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	-0.028	0.011	-9999	-10000	0	0
KIRREL	0.019	0.013	-9999	-0.12	5	5
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.028	0.011	-9999	-10000	0	0
PLCG1	0.017	0.025	-9999	-0.22	5	5
ARRB2	0.013	0.039	-9999	-0.2	15	15
WASL	0.016	0.03	-9999	-0.29	5	5
Nephrin/NEPH1/podocin/CD2AP	0.037	0.043	-9999	-0.15	18	18
ChemicalAbstracts:57-88-5	0	0	-9999	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.026	0.047	-9999	-0.2	19	19
FYN	0.021	0.01	-9999	-10000	0	0
mol:Ca2+	0.045	0.02	-9999	-0.17	3	3
mol:DAG	0.046	0.02	-9999	-0.17	3	3
NPHS2	0.02	0.003	-9999	-10000	0	0
mol:IP3	0.046	0.02	-9999	-0.17	3	3
regulation of endocytosis	0.027	0.045	-9999	-0.16	9	9
Nephrin/NEPH1/podocin/Cholesterol	0.036	0.01	-9999	-10000	0	0
establishment of cell polarity	0.028	0.011	-9999	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2	0.047	0.046	-9999	-0.16	21	21
Nephrin/NEPH1/beta Arrestin2	0.028	0.046	-9999	-0.17	9	9
NPHS1	0.02	0.006	-9999	-0.11	1	1
Nephrin/NEPH1/podocin	0.023	0.04	-9999	-0.13	2	2
TJP1	0.01	0.046	-9999	-0.19	22	22
NCK1	0.014	0.036	-9999	-0.19	14	14
NCK2	0.009	0.053	-9999	-0.28	17	17
heterophilic cell adhesion	0	0	-9999	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.047	0.02	-9999	-0.17	3	3
CD2AP	0.003	0.061	-9999	-0.19	39	39
Nephrin/NEPH1/podocin/GRB2	0.045	0.029	-9999	-0.18	8	8
GRB2	0.014	0.039	-9999	-0.26	10	10
homophilic cell adhesion	0	0	-9999	-10000	0	0
TRPC6	0.021	0.016	-9999	-0.079	1	1
cytoskeleton organization	0.028	0.044	-9999	-0.22	12	12
Nephrin/NEPH1	0.024	0.007	-9999	-10000	0	0
Nephrin/NEPH1/ZO-1	0.032	0.033	-9999	-0.18	10	10

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.025	0.021	-9999	-0.19	2	2
FBXW11	0.011	0.047	-9999	-0.26	14	14
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.011	0.047	-9999	-0.26	14	14
CHUK	0.016	0.024	-9999	-0.15	9	9
NF kappa B2 p100/RelB	0.048	0.033	-9999	-0.12	14	14
NFKB1	0.014	0.038	-9999	-0.22	12	12
MAP3K14	0.017	0.017	-9999	-0.11	9	9
NF kappa B1 p50/RelB	0.024	0.027	-9999	-0.19	7	7
RELB	0.018	0.011	-9999	-0.11	4	4
NFKB2	0.019	0.008	-9999	-0.11	2	2
NF kappa B2 p52/RelB	0.025	0.008	-9999	-10000	0	0
regulation of B cell activation	0.025	0.008	-9999	-10000	0	0

×

Rapid glucocorticoid signaling

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
Gs family/GDP/Gbeta gamma	0.016	0.03	-9999	-0.13	21	21
MAPK9	0.007	0.022	-9999	-0.24	4	4
adrenocorticotropin secretion	0.009	0.01	-9999	-0.07	9	9
GNB1/GNG2	0.006	0.034	-9999	-0.16	21	21
GNB1	0.007	0.061	-9999	-0.29	21	21
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
MAPK14	0.008	0.005	-9999	-10000	0	0
Gs family/GTP	0.012	0.005	-9999	-0.05	3	3
EntrezGene:2778	0	0	-9999	-10000	0	0
vasopressin secretion	0	0	-9999	-10000	0	0
G-protein coupled receptor activity	0	0	-9999	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
glutamate secretion	0	0.001	-9999	-10000	0	0
GNAL	0.018	0.01	-9999	-0.11	3	3
GNG2	0	0	-9999	-10000	0	0
CRH	0.017	0.017	-9999	-0.11	9	9
mol:cortisol	0	0	-9999	-10000	0	0
MAPK8	0.009	0	-9999	-10000	0	0
MAPK11	0.009	0	-9999	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.019	0	-9999	-10000	0	0
ITGB7	0.018	0.01	-9999	-0.11	3	3
ITGA4	0.016	0.019	-9999	-0.11	12	12
alpha4/beta7 Integrin	0.026	0.016	-9999	-0.14	2	2
alpha4/beta1 Integrin	0.026	0.014	-9999	-10000	0	0

×

Visual signal transduction: Rods

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
mol:K +	0.019	0	-9999	-10000	0	0
GNAT1/GTP	0.014	0	-9999	-10000	0	0
Metarhodopsin II/Arrestin	0.026	0.005	-9999	-10000	0	0
PDE6G/GNAT1/GTP	0.026	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.019	0	-9999	-10000	0	0
GRK1	0	0	-9999	-10000	0	0
CNG Channel	0.037	0.008	-9999	-10000	0	0
mol:Na +	0.03	0.004	-9999	-10000	0	0
mol:ADP	0	0	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.023	0.016	-9999	-0.16	1	1
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	0.038	0.005	-9999	-10000	0	0
CNGB1	0.019	0	-9999	-10000	0	0
RDH5	0.017	0.016	-9999	-0.11	8	8
SAG	0.019	0.008	-9999	-0.11	2	2
mol:Ca2+	0.032	0.004	-9999	-10000	0	0
Na + (4 Units)	0.027	0.004	-9999	-10000	0	0
RGS9	0.016	0.02	-9999	-0.11	13	13
GNB1/GNGT1	0.019	0.044	-9999	-0.19	21	21
GNAT1/GDP	0.031	0.015	-9999	-0.12	1	1
GUCY2D	0.019	0	-9999	-10000	0	0
GNGT1	0.019	0.008	-9999	-10000	0	0
GUCY2F	0.019	0	-9999	-10000	0	0
GNB5	0.017	0.019	-9999	-0.14	7	7
mol:GMP (4 units)	0.032	0.007	-9999	-10000	0	0
mol:11-cis-retinal	0.017	0.016	-9999	-0.11	8	8
mol:cGMP	0.026	0	-9999	-10000	0	0
GNB1	0.007	0.061	-9999	-0.29	21	21
Rhodopsin	0.027	0.011	-9999	-10000	0	0
SLC24A1	0.019	0	-9999	-10000	0	0
CNGA1	0.018	0.01	-9999	-0.11	3	3
Metarhodopsin II	0.012	0	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	0.025	0	-9999	-10000	0	0
RGS9BP	0	0	-9999	-10000	0	0
Metarhodopsin II/Transducin	0.018	0.037	-9999	-0.16	21	21
GCAP Family/Ca ++	0.012	0	-9999	-10000	0	0
PDE6A/B	0.027	0.01	-9999	-10000	0	0
mol:Pi	0.022	0.016	-9999	-0.16	1	1
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	0.03	0.034	-9999	-0.14	21	21
PDE6B	0.018	0.013	-9999	-0.11	5	5
PDE6A	0.019	0.006	-9999	-0.11	1	1
PDE6G	0.019	0	-9999	-10000	0	0
RHO	0.019	0	-9999	-10000	0	0
PDE6	0.043	0.017	-9999	-0.11	1	1
GUCA1A	0	0	-9999	-10000	0	0
GC2/GCAP Family	0.025	0	-9999	-10000	0	0
GUCA1C	0	0	-9999	-10000	0	0
GUCA1B	0.019	0	-9999	-10000	0	0

×

Ephrin A reverse signaling

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
MAPKKK cascade	0.025	0.003	-9999	-10000	0	0
EFNA5	0.019	0.006	-9999	-0.11	1	1
FYN	0.02	0.01	-9999	-10000	0	0
neuron projection morphogenesis	0.025	0.003	-9999	-10000	0	0
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	0.026	0.003	-9999	-10000	0	0
EPHA5	0.019	0	-9999	-10000	0	0

×

Class IB PI3K non-lipid kinase events

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
cAMP biosynthetic process	-0.019	-9999	-9999
PI3K Class IB/PDE3B	0.019	-9999	-9999
PDE3B	0.019	-9999	-9999

pid_entity	TCGA.87.5896	TCGA.81.5910	TCGA.76.6285	TCGA.76.6282
109_MAP3K5	-0.052	0.049	0.014	0.035
47_PPARGC1A	0.019	0.019	0.019	-0.11
105_BMP4	0.019	0.019	0.019	0.019
105_BMP6	0.019	0.019	0.019	0.019
105_BMP7	0.019	0.019	0.019	0.019
105_BMP2	0.019	0.019	-0.11	0.019
131_RELN/VLDLR	-0.034	-0.035	0.049	0.049
30_TGFB1/TGF beta receptor Type II	-0.11	0.018	0.02	-0.11
84_STAT5B	-0.052	-0.051	0.019	0.027
84_STAT5A	-0.052	-0.051	0.019	0.011