PARADIGM pathway analysis of mRNASeq expression and copy number data - Stomach Adenocarcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
Reelin signaling pathway	92
FOXA2 and FOXA3 transcription factor networks	75
Effects of Botulinum toxin	54
Lissencephaly gene (LIS1) in neuronal migration and development	51
Signaling events regulated by Ret tyrosine kinase	50
p75(NTR)-mediated signaling	49
Signaling events mediated by Stem cell factor receptor (c-Kit)	48
HIF-1-alpha transcription factor network	44
Wnt signaling	44
Signaling events mediated by the Hedgehog family	40

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
Reelin signaling pathway	0.2217	92	5184	56	-0.24	0.062	1000	-1000	-0.051	-1000
FOXA2 and FOXA3 transcription factor networks	0.1807	75	3469	46	-0.77	0.031	1000	-1000	-0.17	-1000
Effects of Botulinum toxin	0.1301	54	1407	26	-0.15	0.027	1000	-1000	-0.012	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.1229	51	2806	54	-0.19	0.038	1000	-1000	-0.046	-1000
Signaling events regulated by Ret tyrosine kinase	0.1205	50	4177	82	-0.12	0.028	1000	-1000	-0.062	-1000
p75(NTR)-mediated signaling	0.1181	49	6146	125	-0.17	0.072	1000	-1000	-0.073	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.1157	48	3765	78	-0.22	0.073	1000	-1000	-0.064	-1000
HIF-1-alpha transcription factor network	0.1060	44	3381	76	-0.38	0.036	1000	-1000	-0.15	-1000
Wnt signaling	0.1060	44	310	7	-0.08	-0.004	1000	-1000	-0.022	-1000
Signaling events mediated by the Hedgehog family	0.0964	40	2103	52	-0.067	0.043	1000	-1000	-0.046	-1000
IL4-mediated signaling events	0.0964	40	3664	91	-0.68	0.55	1000	-1000	-0.18	-1000
IL23-mediated signaling events	0.0940	39	2381	60	-0.49	0.028	1000	-1000	-0.15	-1000
Syndecan-1-mediated signaling events	0.0916	38	1293	34	-0.15	0.027	1000	-1000	-0.042	-1000
Glypican 2 network	0.0892	37	148	4	-0.006	0.002	1000	-1000	0.009	-1000
Noncanonical Wnt signaling pathway	0.0867	36	936	26	-0.08	0.027	1000	-1000	-0.043	-1000
Fc-epsilon receptor I signaling in mast cells	0.0867	36	3508	97	-0.12	0.042	1000	-1000	-0.06	-1000
EPHB forward signaling	0.0867	36	3112	85	-0.16	0.11	1000	-1000	-0.064	-1000
Visual signal transduction: Cones	0.0843	35	1361	38	-0.065	0.048	1000	-1000	-0.018	-1000
Glypican 1 network	0.0843	35	1715	48	-0.12	0.049	1000	-1000	-0.03	-1000
Syndecan-2-mediated signaling events	0.0795	33	2300	69	-0.16	0.042	1000	-1000	-0.042	-1000
Ephrin B reverse signaling	0.0795	33	1607	48	-0.16	0.089	1000	-1000	-0.033	-1000
TCGA08_p53	0.0795	33	232	7	-0.067	0.045	1000	-1000	-0.006	-1000
BMP receptor signaling	0.0723	30	2493	81	-0.16	0.049	1000	-1000	-0.059	-1000
TCGA08_retinoblastoma	0.0675	28	231	8	-0.086	0.04	1000	-1000	-0.003	-1000
Canonical Wnt signaling pathway	0.0651	27	1391	51	-0.15	0.12	1000	-1000	-0.06	-1000
Endothelins	0.0602	25	2461	96	-0.15	0.042	1000	-1000	-0.066	-1000
BCR signaling pathway	0.0602	25	2506	99	-0.11	0.034	1000	-1000	-0.059	-1000
Nongenotropic Androgen signaling	0.0578	24	1272	52	-0.074	0.043	1000	-1000	-0.042	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0554	23	800	34	-0.022	0.04	1000	-1000	-0.029	-1000
amb2 Integrin signaling	0.0554	23	1967	82	-0.14	0.038	1000	-1000	-0.049	-1000
Glucocorticoid receptor regulatory network	0.0554	23	2710	114	-0.32	0.21	1000	-1000	-0.065	-1000
TCR signaling in naïve CD8+ T cells	0.0554	23	2180	93	-0.12	0.059	1000	-1000	-0.048	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0554	23	2845	120	-0.11	0.09	1000	-1000	-0.05	-1000
Osteopontin-mediated events	0.0530	22	848	38	-0.15	0.039	1000	-1000	-0.052	-1000
Presenilin action in Notch and Wnt signaling	0.0530	22	1378	61	-0.15	0.072	1000	-1000	-0.047	-1000
LPA receptor mediated events	0.0530	22	2343	102	-0.11	0.037	1000	-1000	-0.052	-1000
Ephrin A reverse signaling	0.0506	21	147	7	-0.003	0.016	1000	-1000	-0.017	-1000
S1P5 pathway	0.0482	20	353	17	-0.055	0.029	1000	-1000	-0.016	-1000
Visual signal transduction: Rods	0.0458	19	1027	52	-0.058	0.037	1000	-1000	-0.036	-1000
Plasma membrane estrogen receptor signaling	0.0434	18	1580	86	-0.13	0.046	1000	-1000	-0.051	-1000
S1P4 pathway	0.0434	18	461	25	-0.055	0.044	1000	-1000	-0.027	-1000
Arf6 signaling events	0.0410	17	1070	62	-0.079	0.059	1000	-1000	-0.04	-1000
Integrins in angiogenesis	0.0410	17	1460	84	-0.15	0.061	1000	-1000	-0.041	-1000
LPA4-mediated signaling events	0.0361	15	187	12	-0.053	0.007	1000	-1000	-0.025	-1000
ErbB4 signaling events	0.0361	15	1078	69	-0.11	0.055	1000	-1000	-0.051	-1000
PDGFR-beta signaling pathway	0.0361	15	1469	97	-0.05	0.082	1000	-1000	-0.058	-1000
Regulation of Androgen receptor activity	0.0361	15	1085	70	-0.22	0.032	1000	-1000	-0.058	-1000
IL1-mediated signaling events	0.0337	14	901	62	-0.054	0.055	1000	-1000	-0.045	-1000
Syndecan-3-mediated signaling events	0.0337	14	511	35	-0.16	0.072	1000	-1000	-0.029	-1000
Syndecan-4-mediated signaling events	0.0337	14	973	67	-0.19	0.033	1000	-1000	-0.048	-1000
Aurora B signaling	0.0337	14	947	67	-0.3	0.08	1000	-1000	-0.044	-1000
ErbB2/ErbB3 signaling events	0.0313	13	897	65	-0.099	0.04	1000	-1000	-0.067	-1000
Coregulation of Androgen receptor activity	0.0313	13	1023	76	-0.087	0.05	1000	-1000	-0.024	-1000
IL12-mediated signaling events	0.0313	13	1206	87	-0.13	0.034	1000	-1000	-0.1	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0313	13	686	52	-0.14	0.056	1000	-1000	-0.064	-1000
S1P1 pathway	0.0313	13	486	36	-0.057	0.028	1000	-1000	-0.052	-1000
Calcium signaling in the CD4+ TCR pathway	0.0313	13	403	31	-0.11	0.027	1000	-1000	-0.056	-1000
IL27-mediated signaling events	0.0313	13	694	51	-0.24	0.062	1000	-1000	-0.065	-1000
IGF1 pathway	0.0313	13	791	57	-0.021	0.053	1000	-1000	-0.047	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0313	13	440	33	-0.088	0.064	1000	-1000	-0.041	-1000
Cellular roles of Anthrax toxin	0.0289	12	491	39	-0.022	0.027	1000	-1000	-0.023	-1000
PLK1 signaling events	0.0289	12	1071	85	-0.05	0.05	1000	-1000	-0.038	-1000
S1P3 pathway	0.0289	12	510	42	-0.054	0.046	1000	-1000	-0.047	-1000
JNK signaling in the CD4+ TCR pathway	0.0265	11	202	17	-0.032	0.056	1000	-1000	-0.037	-1000
Signaling events mediated by PTP1B	0.0265	11	863	76	-0.14	0.046	1000	-1000	-0.044	-1000
Nectin adhesion pathway	0.0265	11	708	63	-0.24	0.051	1000	-1000	-0.058	-1000
Ceramide signaling pathway	0.0265	11	883	76	-0.022	0.072	1000	-1000	-0.043	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0265	11	412	37	-0.086	0.062	1000	-1000	-0.034	-1000
ceramide signaling pathway	0.0265	11	542	49	0	0.04	1000	-1000	-0.046	-1000
Signaling mediated by p38-alpha and p38-beta	0.0265	11	516	44	-0.12	0.028	1000	-1000	-0.036	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0265	11	748	68	-0.21	0.032	1000	-1000	-0.11	-1000
EGFR-dependent Endothelin signaling events	0.0265	11	243	21	-0.028	0.04	1000	-1000	-0.043	-1000
FOXM1 transcription factor network	0.0265	11	599	51	-0.11	0.037	1000	-1000	-0.18	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0241	10	880	85	-0.035	0.041	1000	-1000	-0.055	-1000
FAS signaling pathway (CD95)	0.0241	10	497	47	-0.093	0.04	1000	-1000	-0.043	-1000
Ras signaling in the CD4+ TCR pathway	0.0241	10	170	17	0	0.043	1000	-1000	-0.027	-1000
Caspase cascade in apoptosis	0.0217	9	680	74	-0.048	0.063	1000	-1000	-0.04	-1000
Class I PI3K signaling events mediated by Akt	0.0217	9	630	68	-0.042	0.048	1000	-1000	-0.044	-1000
Signaling mediated by p38-gamma and p38-delta	0.0217	9	146	15	-0.05	0.027	1000	-1000	-0.037	-1000
Retinoic acid receptors-mediated signaling	0.0217	9	524	58	-0.15	0.05	1000	-1000	-0.049	-1000
Regulation of p38-alpha and p38-beta	0.0217	9	488	54	-0.041	0.06	1000	-1000	-0.052	-1000
IL6-mediated signaling events	0.0217	9	680	75	-0.18	0.04	1000	-1000	-0.088	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0217	9	667	74	-0.1	0.064	1000	-1000	-0.061	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0217	9	814	88	-0.077	0.063	1000	-1000	-0.079	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0193	8	238	28	-0.055	0.047	1000	-1000	-0.021	-1000
IFN-gamma pathway	0.0193	8	588	68	-0.066	0.039	1000	-1000	-0.059	-1000
IL2 signaling events mediated by PI3K	0.0193	8	496	58	-0.077	0.051	1000	-1000	-0.069	-1000
Class I PI3K signaling events	0.0193	8	603	73	-0.041	0.046	1000	-1000	-0.047	-1000
FoxO family signaling	0.0169	7	495	64	-0.1	0.057	1000	-1000	-0.08	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0169	7	325	45	-0.003	0.069	1000	-1000	-0.053	-1000
Regulation of nuclear SMAD2/3 signaling	0.0145	6	861	136	-0.085	0.068	1000	-1000	-0.048	-1000
PLK2 and PLK4 events	0.0145	6	20	3	0.006	0.023	1000	-1000	-0.015	-1000
Hedgehog signaling events mediated by Gli proteins	0.0145	6	451	65	-0.055	0.061	1000	-1000	-0.051	-1000
Aurora A signaling	0.0145	6	416	60	-0.08	0.055	1000	-1000	-0.02	-1000
Aurora C signaling	0.0145	6	44	7	0	0.035	1000	-1000	-0.021	-1000
E-cadherin signaling in the nascent adherens junction	0.0145	6	529	76	-0.01	0.059	1000	-1000	-0.057	-1000
Regulation of Telomerase	0.0145	6	641	102	-0.078	0.063	1000	-1000	-0.059	-1000
Rapid glucocorticoid signaling	0.0145	6	127	20	-0.012	0.035	1000	-1000	-0.006	-1000
Thromboxane A2 receptor signaling	0.0120	5	540	105	-0.053	0.04	1000	-1000	-0.061	-1000
EPO signaling pathway	0.0120	5	322	55	0.007	0.057	1000	-1000	-0.049	-1000
PDGFR-alpha signaling pathway	0.0120	5	244	44	-0.042	0.063	1000	-1000	-0.045	-1000
mTOR signaling pathway	0.0120	5	306	53	-0.031	0.043	1000	-1000	-0.041	-1000
Signaling events mediated by HDAC Class III	0.0120	5	212	40	-0.049	0.05	1000	-1000	-0.019	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0120	5	470	83	-0.13	0.054	1000	-1000	-0.043	-1000
TCGA08_rtk_signaling	0.0120	5	143	26	-0.041	0.073	1000	-1000	-0.028	-1000
IL2 signaling events mediated by STAT5	0.0120	5	110	22	-0.011	0.038	1000	-1000	-0.059	-1000
Arf6 trafficking events	0.0120	5	356	71	-0.091	0.05	1000	-1000	-0.034	-1000
Insulin Pathway	0.0120	5	384	74	-0.037	0.076	1000	-1000	-0.049	-1000
Signaling events mediated by PRL	0.0120	5	174	34	-0.048	0.04	1000	-1000	-0.048	-1000
E-cadherin signaling in keratinocytes	0.0120	5	219	43	-0.031	0.047	1000	-1000	-0.039	-1000
E-cadherin signaling events	0.0120	5	27	5	0.018	0.042	1000	-1000	0.007	-1000
p38 MAPK signaling pathway	0.0120	5	259	44	-0.047	0.057	1000	-1000	-0.033	-1000
Insulin-mediated glucose transport	0.0096	4	158	32	-0.075	0.052	1000	-1000	-0.037	-1000
VEGFR1 specific signals	0.0096	4	249	56	-0.014	0.06	1000	-1000	-0.049	-1000
Class IB PI3K non-lipid kinase events	0.0072	3	9	3	-0.025	0.025	1000	-1000	-0.01	-1000
Canonical NF-kappaB pathway	0.0048	2	114	39	0	0.058	1000	-1000	-0.045	-1000
a4b1 and a4b7 Integrin signaling	0.0048	2	13	5	0.025	0.036	1000	-1000	0.004	-1000
Arf6 downstream pathway	0.0048	2	119	43	-0.043	0.047	1000	-1000	-0.028	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0048	2	342	125	0	0.07	1000	-1000	-0.061	-1000
Signaling events mediated by HDAC Class II	0.0024	1	123	75	-0.027	0.07	1000	-1000	-0.035	-1000
BARD1 signaling events	0.0024	1	74	57	-0.059	0.066	1000	-1000	-0.045	-1000
TRAIL signaling pathway	0.0024	1	79	48	0	0.058	1000	-1000	-0.038	-1000
HIF-2-alpha transcription factor network	0.0024	1	79	43	-0.05	0.052	1000	-1000	-0.085	-1000
Signaling events mediated by HDAC Class I	0.0024	1	195	104	-0.052	0.066	1000	-1000	-0.046	-1000
Paxillin-dependent events mediated by a4b1	0.0024	1	60	36	-0.051	0.053	1000	-1000	-0.042	-1000
Atypical NF-kappaB pathway	0.0024	1	38	31	0	0.036	1000	-1000	-0.029	-1000
Arf1 pathway	0.0024	1	85	54	-0.001	0.048	1000	-1000	-0.025	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	16	23	0.011	0.047	1000	-1000	-0.04	-1000
Circadian rhythm pathway	0.0000	0	17	22	-0.008	0.062	1000	-1000	-0.04	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	10	27	0	0.059	1000	-1000	-0.036	-1000
Alternative NF-kappaB pathway	0.0000	0	4	13	0	0.072	1000	-1000	0	-1000
Total	NA	2120	125653	7203	-13	7.1	131000	-131000	-6.3	-131000

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.036	0.03	-10000	0	-0.25	4	4
VLDLR	-0.021	0.13	-10000	0	-0.38	45	45
CRKL	0.027	0.006	-10000	0	-10000	0	0
LRPAP1	0.026	0.007	-10000	0	-10000	0	0
FYN	0.027	0.005	-10000	0	-10000	0	0
ITGA3	0.026	0.027	-10000	0	-0.35	2	2
RELN/VLDLR/Fyn	-0.046	0.15	-10000	0	-0.28	116	116
MAPK8IP1/MKK7/MAP3K11/JNK1	0.062	0.057	-10000	0	-10000	0	0
AKT1	-0.16	0.17	-10000	0	-0.4	108	108
MAP2K7	0.027	0.006	-10000	0	-10000	0	0
RAPGEF1	0.027	0.005	-10000	0	-10000	0	0
DAB1	-0.19	0.2	-10000	0	-0.38	213	213
RELN/LRP8/DAB1	-0.2	0.2	-10000	0	-0.31	283	283
LRPAP1/LRP8	-0.072	0.14	-10000	0	-0.24	161	161
RELN/LRP8/DAB1/Fyn	-0.19	0.19	-10000	0	-0.3	275	275
DAB1/alpha3/beta1 Integrin	-0.19	0.19	-10000	0	-0.4	148	148
long-term memory	-0.24	0.22	-10000	0	-0.45	174	174
DAB1/LIS1	-0.19	0.2	-10000	0	-0.41	150	150
DAB1/CRLK/C3G	-0.19	0.19	-10000	0	-0.4	147	147
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
DAB1/NCK2	-0.19	0.2	-10000	0	-0.42	149	149
ARHGEF2	0.027	0.006	-10000	0	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	-0.068	0.17	-10000	0	-0.38	95	95
CDK5R1	0.024	0.038	-10000	0	-0.35	4	4
RELN	-0.082	0.18	-10000	0	-0.38	108	108
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
RELN/LRP8/Fyn	-0.11	0.17	-10000	0	-0.27	198	198
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.23	0.22	-10000	0	-0.44	175	175
MAPK8	0.027	0.005	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.15	0.18	-10000	0	-0.28	239	239
ITGB1	0.026	0.02	-10000	0	-0.35	1	1
MAP1B	-0.22	0.19	-10000	0	-0.36	229	229
RELN/LRP8	-0.11	0.17	-10000	0	-0.27	197	197
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.2	0.2	-10000	0	-0.42	156	156
PI3K	0.036	0.014	-10000	0	-10000	0	0
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.037	0.026	-10000	0	-0.25	3	3
RAP1A	-0.19	0.17	0.23	3	-0.38	146	149
PAFAH1B1	0.026	0.008	-10000	0	-10000	0	0
MAPK8IP1	0.009	0.084	-10000	0	-0.38	18	18
CRLK/C3G	0.039	0.011	-10000	0	-10000	0	0
GRIN2B	-0.015	0.12	-10000	0	-0.35	43	43
NCK2	0.028	0.004	-10000	0	-10000	0	0
neuron differentiation	-0.16	0.17	-10000	0	-0.36	138	138
neuron adhesion	-0.18	0.17	0.29	4	-0.38	138	142
LRP8	-0.12	0.19	-10000	0	-0.35	165	165
GSK3B	-0.15	0.17	-10000	0	-0.39	104	104
RELN/VLDLR/DAB1/Fyn	-0.14	0.17	-10000	0	-0.27	236	236
MAP3K11	0.027	0.005	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.17	0.19	-10000	0	-0.3	233	233
CDK5	0.027	0.006	-10000	0	-10000	0	0
MAPT	-0.043	0.19	0.85	8	-0.33	86	94
neuron migration	-0.22	0.18	0.22	1	-0.41	150	151
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.16	0.17	-10000	0	-0.36	143	143
RELN/VLDLR	-0.11	0.18	-10000	0	-0.28	188	188

×

FOXA2 and FOXA3 transcription factor networks

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.51	0.36	-9999	-0.93	128	128
PCK1	-0.36	0.34	-9999	-0.94	76	76
HNF4A	-0.59	0.44	-9999	-1.1	159	159
KCNJ11	-0.49	0.35	-9999	-0.96	102	102
AKT1	-0.28	0.2	-9999	-0.7	37	37
response to starvation	-0.025	0.037	-9999	-0.22	4	4
DLK1	-0.52	0.38	-9999	-1	114	114
NKX2-1	-0.2	0.15	-9999	-0.39	69	69
ACADM	-0.51	0.36	-9999	-0.94	121	121
TAT	-0.36	0.34	-9999	-1.1	55	55
CEBPB	0.002	0.037	-9999	-0.17	1	1
CEBPA	-0.005	0.059	-9999	-0.34	6	6
TTR	-0.46	0.49	-9999	-1.2	120	120
PKLR	-0.53	0.37	-9999	-0.96	130	130
APOA1	-0.77	0.58	-9999	-1.4	171	171
CPT1C	-0.52	0.36	-9999	-0.95	126	126
ALAS1	-0.23	0.15	-9999	-0.6	8	8
TFRC	-0.34	0.25	-9999	-0.87	37	37
FOXF1	0.013	0.072	-9999	-0.38	13	13
NF1	0.031	0.005	-9999	-10000	0	0
HNF1A (dimer)	-0.073	0.11	-9999	-0.26	57	57
CPT1A	-0.51	0.35	-9999	-0.94	120	120
HMGCS1	-0.49	0.36	-9999	-0.94	114	114
NR3C1	-0.018	0.074	-9999	-0.28	12	12
CPT1B	-0.51	0.36	-9999	-0.94	124	124
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.025	0.027	-9999	-10000	0	0
GCK	-0.52	0.37	-9999	-0.95	133	133
CREB1	-0.014	0.068	-9999	-0.19	12	12
IGFBP1	-0.32	0.21	-9999	-0.73	33	33
PDX1	-0.3	0.28	-9999	-1.1	23	23
UCP2	-0.51	0.35	-9999	-0.94	121	121
ALDOB	-0.6	0.43	-9999	-1	164	164
AFP	-0.077	0.13	-9999	-0.42	30	30
BDH1	-0.51	0.36	-9999	-0.95	119	119
HADH	-0.48	0.35	-9999	-0.95	104	104
F2	-0.61	0.43	-9999	-1.2	119	119
HNF1A	-0.073	0.11	-9999	-0.26	57	57
G6PC	-0.16	0.34	-9999	-1.1	45	45
SLC2A2	-0.71	0.54	-9999	-1.2	204	204
INS	0.014	0.05	-9999	-10000	0	0
FOXA1	-0.04	0.11	-9999	-0.33	33	33
FOXA3	-0.072	0.12	-9999	-0.37	33	33
FOXA2	-0.56	0.39	-9999	-1	130	130
ABCC8	-0.62	0.43	-9999	-1	174	174
ALB	-0.088	0.14	-9999	-0.44	31	31

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.003	0.03	-10000	0	-0.24	6	6
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	-0.055	0.14	-10000	0	-0.27	122	122
STXBP1	0.022	0.042	-10000	0	-0.35	5	5
ACh/CHRNA1	-0.1	0.12	-10000	0	-0.22	195	195
RAB3GAP2/RIMS1/UNC13B	-0.03	0.12	-10000	0	-0.23	117	117
mol:Ca2+	0	0	-10000	0	-10000	0	0
UniProt:P30996	0	0	-10000	0	-10000	0	0
UniProt:Q60393	0	0	-10000	0	-10000	0	0
CST086	0	0	-10000	0	-10000	0	0
RIMS1	-0.099	0.19	-10000	0	-0.38	125	125
mol:ACh	-0.014	0.055	0.082	37	-0.11	74	111
RAB3GAP2	0.027	0.005	-10000	0	-10000	0	0
STX1A/SNAP25/VAMP2	-0.048	0.12	-10000	0	-0.28	44	44
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	-0.1	0.12	-10000	0	-0.22	195	195
UNC13B	0.026	0.008	-10000	0	-10000	0	0
CHRNA1	-0.15	0.19	-10000	0	-0.35	188	188
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	-0.04	0.11	-10000	0	-0.23	83	83
SNAP25	-0.042	0.095	-10000	0	-0.23	82	82
VAMP2	0.005	0.001	-10000	0	-10000	0	0
SYT1	-0.049	0.15	-10000	0	-0.36	80	80
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.019	0.036	-10000	0	-0.2	10	10
STX1A/SNAP25 fragment 1/VAMP2	-0.048	0.12	-10000	0	-0.28	44	44

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.027	0.006	-10000	0	-10000	0	0
VLDLR	-0.021	0.13	-10000	0	-0.38	45	45
LRPAP1	0.026	0.007	-10000	0	-10000	0	0
NUDC	0.026	0.007	-10000	0	-10000	0	0
RELN/LRP8	-0.11	0.17	-10000	0	-0.27	197	197
CaM/Ca2+	0.02	0.004	-10000	0	-10000	0	0
KATNA1	0.027	0.006	-10000	0	-10000	0	0
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	-0.1	0.15	0.18	11	-0.31	98	109
IQGAP1/CaM	0.038	0.012	-10000	0	-10000	0	0
DAB1	-0.19	0.2	-10000	0	-0.38	213	213
IQGAP1	0.026	0.007	-10000	0	-10000	0	0
PLA2G7	-0.14	0.19	-10000	0	-0.35	176	176
CALM1	0.027	0.005	-10000	0	-10000	0	0
DYNLT1	0.027	0.006	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	-0.072	0.14	-10000	0	-0.24	161	161
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0.027	0.019	-10000	0	-0.35	1	1
CDK5R1	0.024	0.038	-10000	0	-0.35	4	4
LIS1/Poliovirus Protein 3A	0.008	0.004	-10000	0	-10000	0	0
CDK5R2	-0.063	0.17	-10000	0	-0.38	91	91
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.16	0.19	-10000	0	-0.31	239	239
YWHAE	0.026	0.008	-10000	0	-10000	0	0
NDEL1/14-3-3 E	-0.11	0.16	0.29	5	-0.33	93	98
MAP1B	0.002	0.021	-10000	0	-0.24	1	1
RAC1	0.011	0.007	-10000	0	-10000	0	0
p35/CDK5	-0.091	0.14	0.18	14	-0.34	61	75
RELN	-0.082	0.18	-10000	0	-0.38	108	108
PAFAH/LIS1	-0.07	0.11	-10000	0	-0.21	166	166
LIS1/CLIP170	0.025	0.017	-10000	0	-0.21	1	1
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.089	0.13	-10000	0	-0.3	54	54
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.18	0.21	-10000	0	-0.46	115	115
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	-0.12	0.16	0.21	10	-0.35	101	111
LIS1/IQGAP1	0.024	0.013	-10000	0	-10000	0	0
RHOA	0.012	0.006	-10000	0	-10000	0	0
PAFAH1B1	0.011	0.005	-10000	0	-10000	0	0
PAFAH1B3	0.027	0.006	-10000	0	-10000	0	0
PAFAH1B2	0.027	0.006	-10000	0	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0.013	0.037	-10000	0	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.1	0.16	0.31	4	-0.32	95	99
LRP8	-0.12	0.19	-10000	0	-0.35	165	165
NDEL1/Katanin 60	-0.11	0.16	0.29	5	-0.33	95	100
P39/CDK5	-0.13	0.16	0.18	13	-0.36	100	113
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.024	0.013	-10000	0	-10000	0	0
CDK5	-0.11	0.14	0.18	17	-0.35	60	77
PPP2R5D	0.026	0.007	-10000	0	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.021	0.014	-10000	0	-0.18	1	1
CSNK2A1	0.025	0.009	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.13	0.17	-10000	0	-0.36	98	98
RELN/VLDLR	-0.11	0.18	-10000	0	-0.28	188	188
CDC42	0.011	0.006	-10000	0	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.013	0.075	-10000	0	-0.41	10	10
Crk/p130 Cas/Paxillin	-0.083	0.13	-10000	0	-0.33	46	46
JUN	-0.072	0.13	-10000	0	-0.34	48	48
HRAS	0.026	0.007	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.053	0.16	-10000	0	-0.25	144	144
RAP1A	0.027	0.005	-10000	0	-10000	0	0
FRS2	0.026	0.007	-10000	0	-10000	0	0
RAP1A/GDP	0.02	0.003	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.057	0.16	-10000	0	-0.25	152	152
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.028	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.026	0.008	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.043	0.12	-10000	0	-0.21	137	137
RHOA	0.027	0.006	-10000	0	-10000	0	0
RAP1A/GTP	-0.048	0.14	-10000	0	-0.35	37	37
GRB7	0.019	0.044	-10000	0	-0.37	5	5
RET51/GFRalpha1/GDNF	-0.055	0.16	-10000	0	-0.25	150	150
MAPKKK cascade	-0.065	0.14	-10000	0	-0.37	36	36
BCAR1	0.027	0.006	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.04	0.12	-10000	0	-0.22	131	131
lamellipodium assembly	-0.069	0.12	-10000	0	-0.3	48	48
RET51/GFRalpha1/GDNF/SHC	-0.053	0.16	-10000	0	-0.25	144	144
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.038	0.12	-10000	0	-0.22	127	127
RET9/GFRalpha1/GDNF/Shank3	-0.04	0.12	-10000	0	-0.21	131	131
MAPK3	-0.075	0.12	0.19	20	-0.35	35	55
DOK1	0.027	0.019	-10000	0	-0.35	1	1
DOK6	0.017	0.053	-10000	0	-0.36	8	8
PXN	0.027	0.005	-10000	0	-10000	0	0
neurite development	-0.063	0.12	0.3	1	-0.33	34	35
DOK5	0.006	0.077	-10000	0	-0.36	17	17
GFRA1	-0.12	0.2	-10000	0	-0.38	142	142
MAPK8	-0.074	0.13	-10000	0	-0.35	49	49
HRAS/GTP	-0.063	0.16	-10000	0	-0.32	74	74
tube development	-0.038	0.12	0.21	1	-0.2	121	122
MAPK1	-0.072	0.13	0.2	23	-0.35	35	58
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.051	0.11	-10000	0	-0.23	57	57
Rac1/GDP	0.019	0.006	-10000	0	-10000	0	0
SRC	0.024	0.01	-10000	0	-10000	0	0
PDLIM7	0.022	0.042	-10000	0	-0.35	5	5
RET51/GFRalpha1/GDNF/Dok6	-0.042	0.14	-10000	0	-0.28	67	67
SHC1	0.027	0.005	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.055	0.16	-10000	0	-0.25	147	147
RET51/GFRalpha1/GDNF/Dok5	-0.054	0.14	-10000	0	-0.25	136	136
PRKCA	0.027	0.005	-10000	0	-10000	0	0
HRAS/GDP	0.02	0.005	-10000	0	-10000	0	0
CREB1	-0.078	0.14	-10000	0	-0.38	43	43
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.05	0.11	-10000	0	-0.21	122	122
RET51/GFRalpha1/GDNF/Grb7	-0.05	0.15	-10000	0	-0.25	131	131
mol:GDP	0	0	-10000	0	-10000	0	0
RET	-0.027	0.14	-10000	0	-0.37	56	56
DOK4	0.026	0.021	-10000	0	-0.38	1	1
JNK cascade	-0.071	0.13	-10000	0	-0.33	48	48
RET9/GFRalpha1/GDNF/FRS2	-0.04	0.12	-10000	0	-0.22	128	128
SHANK3	0.026	0.007	-10000	0	-10000	0	0
RASA1	0.025	0.008	-10000	0	-10000	0	0
NCK1	0.027	0.005	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.051	0.11	-10000	0	-0.21	124	124
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.07	0.14	-10000	0	-0.37	43	43
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.073	0.14	-10000	0	-0.29	91	91
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.076	0.15	-10000	0	-0.43	43	43
PI3K	-0.1	0.18	-10000	0	-0.45	52	52
SOS1	0.028	0.003	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.03	0.12	-10000	0	-0.2	127	127
GRB10	0.026	0.02	-10000	0	-0.35	1	1
activation of MAPKK activity	-0.061	0.13	-10000	0	-0.33	41	41
RET51/GFRalpha1/GDNF/FRS2	-0.057	0.16	-10000	0	-0.26	135	135
GAB1	0.027	0.006	-10000	0	-10000	0	0
IRS1	0.027	0.021	-10000	0	-0.38	1	1
IRS2	0.012	0.074	-10000	0	-0.38	14	14
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.075	0.16	-10000	0	-0.42	47	47
RET51/GFRalpha1/GDNF/PKC alpha	-0.057	0.16	-10000	0	-0.25	149	149
GRB2	0.027	0.005	-10000	0	-10000	0	0
PRKACA	0.027	0.005	-10000	0	-10000	0	0
GDNF	0.012	0.068	-10000	0	-0.38	12	12
RAC1	0.026	0.008	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.056	0.16	-10000	0	-0.26	138	138
Rac1/GTP	-0.077	0.15	-10000	0	-0.36	47	47
RET9/GFRalpha1/GDNF	-0.055	0.13	-10000	0	-0.24	132	132
GFRalpha1/GDNF	-0.068	0.15	-10000	0	-0.28	132	132

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.04	0.01	-10000	0	-10000	0	0
Necdin/E2F1	0.025	0.058	-10000	0	-0.27	14	14
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.026	0.15	-10000	0	-0.41	22	22
NGF (dimer)/p75(NTR)/BEX1	-0.14	0.19	-10000	0	-0.29	235	235
NT-4/5 (dimer)/p75(NTR)	-0.074	0.15	-10000	0	-0.27	150	150
IKBKB	0.025	0.009	-10000	0	-10000	0	0
AKT1	-0.065	0.12	0.19	20	-0.37	17	37
IKBKG	0.027	0.006	-10000	0	-10000	0	0
BDNF	0.017	0.062	-10000	0	-0.36	11	11
MGDIs/NGR/p75(NTR)/LINGO1	-0.053	0.14	-10000	0	-0.23	153	153
FURIN	0.027	0.006	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.04	0.13	-10000	0	-0.23	136	136
LINGO1	-0.005	0.11	-10000	0	-0.35	35	35
Sortilin/TRAF6/NRIF	0.03	0.027	-10000	0	-10000	0	0
proBDNF (dimer)	0.017	0.062	-10000	0	-0.36	11	11
NTRK1	0.009	0.084	-10000	0	-0.38	18	18
RTN4R	0.024	0.033	-10000	0	-0.35	3	3
neuron apoptosis	-0.071	0.16	0.31	2	-0.51	22	24
IRAK1	0.027	0.005	-10000	0	-10000	0	0
SHC1	-0.07	0.13	-10000	0	-0.25	130	130
ARHGDIA	0.027	0.005	-10000	0	-10000	0	0
RhoA/GTP	0.02	0.004	-10000	0	-10000	0	0
Gamma Secretase	0.072	0.03	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.035	0.15	-10000	0	-0.24	135	135
MAGEH1	0.021	0.053	-10000	0	-0.38	7	7
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.037	0.15	-10000	0	-0.24	137	137
Mammalian IAPs/DIABLO	0.063	0.036	-10000	0	-10000	0	0
proNGF (dimer)	0.003	0.096	-10000	0	-0.38	24	24
MAGED1	0.025	0.035	-10000	0	-0.38	3	3
APP	0.026	0.008	-10000	0	-10000	0	0
NT-4/5 (dimer)	0	0.092	-10000	0	-0.35	26	26
ZNF274	0.023	0.041	-10000	0	-0.38	4	4
RhoA/GDP/RHOGDI	-0.046	0.12	-10000	0	-0.22	134	134
NGF	0.003	0.096	-10000	0	-0.38	24	24
cell cycle arrest	-0.042	0.12	0.29	6	-0.34	18	24
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.04	0.11	-10000	0	-0.34	24	24
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.049	0.13	-10000	0	-0.23	147	147
NCSTN	0.027	0.005	-10000	0	-10000	0	0
mol:GTP	-0.048	0.15	-10000	0	-0.25	136	136
PSENEN	0.027	0.007	-10000	0	-10000	0	0
mol:ceramide	-0.061	0.12	0.18	5	-0.24	115	120
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.035	0.1	-10000	0	-0.3	33	33
p75(NTR)/beta APP	-0.058	0.14	-10000	0	-0.27	130	130
BEX1	-0.14	0.2	-10000	0	-0.38	163	163
mol:GDP	-0.087	0.12	-10000	0	-0.25	136	136
NGF (dimer)	-0.075	0.13	-10000	0	-0.2	198	198
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.036	0.14	-10000	0	-0.22	147	147
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
RAC1/GTP	-0.036	0.12	-10000	0	-0.21	128	128
MYD88	0.027	0.005	-10000	0	-10000	0	0
CHUK	0.027	0.006	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.048	0.15	-10000	0	-0.25	136	136
RHOB	0.028	0.003	-10000	0	-10000	0	0
RHOA	0.027	0.006	-10000	0	-10000	0	0
MAGE-G1/E2F1	0.029	0.043	-10000	0	-0.24	9	9
NT3 (dimer)	-0.007	0.11	-10000	0	-0.38	33	33
TP53	-0.059	0.1	0.31	4	-0.35	6	10
PRDM4	-0.064	0.12	0.18	5	-0.24	119	124
BDNF (dimer)	-0.17	0.15	-10000	0	-0.36	102	102
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
SORT1	0.027	0.005	-10000	0	-10000	0	0
activation of caspase activity	-0.029	0.15	-10000	0	-0.4	22	22
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.03	0.14	-10000	0	-0.23	130	130
RHOC	0.027	0.005	-10000	0	-10000	0	0
XIAP	0.028	0.004	-10000	0	-10000	0	0
MAPK10	-0.09	0.17	0.27	6	-0.43	52	58
DIABLO	0.027	0.005	-10000	0	-10000	0	0
SMPD2	-0.061	0.12	0.18	5	-0.24	115	120
APH1B	0.027	0.005	-10000	0	-10000	0	0
APH1A	0.027	0.006	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.047	0.15	-10000	0	-0.25	136	136
PSEN1	0.027	0.005	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.039	0.01	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.078	0.16	-10000	0	-0.3	144	144
MAPK8	-0.065	0.14	0.29	7	-0.36	27	34
MAPK9	-0.068	0.14	0.28	6	-0.36	29	35
APAF1	0.028	0.004	-10000	0	-10000	0	0
NTF3	-0.007	0.11	-10000	0	-0.38	33	33
NTF4	0	0.092	-10000	0	-0.35	26	26
NDN	0.017	0.064	-10000	0	-0.38	10	10
RAC1/GDP	0.019	0.006	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.022	0.13	-10000	0	-0.36	18	18
p75 CTF/Sortilin/TRAF6/NRIF	0.061	0.036	-10000	0	-0.21	4	4
RhoA-B-C/GTP	-0.048	0.15	-10000	0	-0.25	136	136
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.014	0.13	-10000	0	-0.37	6	6
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.024	0.13	-10000	0	-0.21	110	110
PRKACB	0.026	0.029	-10000	0	-0.38	2	2
proBDNF (dimer)/p75 ECD	0.032	0.047	-10000	0	-0.25	11	11
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.021	0.047	-10000	0	-0.36	6	6
BIRC2	0.027	0.006	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.043	0.14	0.25	5	-0.27	79	84
BAD	-0.081	0.16	0.25	11	-0.36	57	68
RIPK2	0.024	0.01	-10000	0	-10000	0	0
NGFR	-0.1	0.19	-10000	0	-0.38	130	130
CYCS	-0.072	0.11	0.24	6	-0.38	17	23
ADAM17	0.028	0.004	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.021	0.13	-10000	0	-0.23	111	111
BCL2L11	-0.081	0.16	0.25	12	-0.36	57	69
BDNF (dimer)/p75(NTR)	-0.064	0.15	-10000	0	-0.27	138	138
PI3K	-0.034	0.14	-10000	0	-0.24	107	107
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.031	0.14	-10000	0	-0.23	134	134
NDNL2	0.027	0.005	-10000	0	-10000	0	0
YWHAE	0.026	0.008	-10000	0	-10000	0	0
PRKCI	0.024	0.027	-10000	0	-0.35	2	2
NGF (dimer)/p75(NTR)	-0.072	0.16	-10000	0	-0.3	136	136
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.033	0.15	-10000	0	-0.24	134	134
TRAF6	0.027	0.005	-10000	0	-10000	0	0
RAC1	0.026	0.008	-10000	0	-10000	0	0
PRKCZ	0.026	0.007	-10000	0	-10000	0	0
PLG	0.015	0.041	-10000	0	-0.35	5	5
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.07	0.14	-10000	0	-0.26	117	117
SQSTM1	0.027	0.006	-10000	0	-10000	0	0
NGFRAP1	0.018	0.064	-10000	0	-0.38	10	10
CASP3	-0.08	0.15	0.25	10	-0.35	58	68
E2F1	0.016	0.056	-10000	0	-0.35	9	9
CASP9	0.027	0.006	-10000	0	-10000	0	0
IKK complex	-0.012	0.13	-10000	0	-0.36	20	20
NGF (dimer)/TRKA	0.008	0.095	-10000	0	-0.28	39	39
MMP7	-0.15	0.19	-10000	0	-0.35	193	193
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.021	0.14	-10000	0	-0.38	20	20
MMP3	-0.16	0.19	-10000	0	-0.36	199	199
APAF-1/Caspase 9	-0.07	0.083	-10000	0	-0.32	16	16

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	-0.065	0.16	0.3	2	-0.39	75	77
CRKL	-0.068	0.16	0.27	1	-0.39	78	79
HRAS	-0.048	0.16	-10000	0	-0.35	66	66
mol:PIP3	-0.055	0.16	-10000	0	-0.36	70	70
SPRED1	0.027	0.006	-10000	0	-10000	0	0
SPRED2	0.028	0.003	-10000	0	-10000	0	0
GAB1	-0.07	0.17	-10000	0	-0.4	80	80
FOXO3	-0.058	0.17	0.35	1	-0.38	71	72
AKT1	-0.062	0.18	0.26	1	-0.4	80	81
BAD	-0.058	0.17	0.25	1	-0.38	73	74
megakaryocyte differentiation	-0.09	0.18	-10000	0	-0.42	80	80
GSK3B	-0.056	0.17	0.27	2	-0.37	70	72
RAF1	-0.041	0.13	0.26	2	-0.34	20	22
SHC1	0.027	0.005	-10000	0	-10000	0	0
STAT3	-0.07	0.17	-10000	0	-0.4	79	79
STAT1	-0.18	0.39	-10000	0	-0.95	81	81
HRAS/SPRED1	-0.029	0.14	0.26	1	-0.33	24	25
cell proliferation	-0.07	0.17	-10000	0	-0.39	81	81
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
TEC	0.027	0.006	-10000	0	-10000	0	0
RPS6KB1	-0.062	0.18	-10000	0	-0.4	79	79
HRAS/SPRED2	-0.029	0.14	0.26	1	-0.35	20	21
LYN/TEC/p62DOK	-0.034	0.18	-10000	0	-0.39	66	66
MAPK3	-0.027	0.1	0.22	3	-0.28	12	15
STAP1	-0.09	0.19	-10000	0	-0.44	82	82
GRAP2	0.016	0.067	-10000	0	-0.38	11	11
JAK2	-0.15	0.36	-10000	0	-0.84	81	81
STAT1 (dimer)	-0.17	0.38	-10000	0	-0.92	81	81
mol:Gleevec	0.002	0.007	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.039	0.19	-10000	0	-0.4	76	76
actin filament polymerization	-0.069	0.16	-10000	0	-0.4	72	72
LYN	0.025	0.009	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.12	0.25	-10000	0	-0.6	82	82
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.037	0.16	0.27	1	-0.37	70	71
PI3K	-0.041	0.18	-10000	0	-0.39	71	71
PTEN	0.026	0.008	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.19	0.45	-10000	0	-1.1	82	82
MAPK8	-0.071	0.17	-10000	0	-0.4	80	80
STAT3 (dimer)	-0.069	0.17	-10000	0	-0.4	80	80
positive regulation of transcription	-0.021	0.085	0.19	4	-0.23	12	16
mol:GDP	-0.043	0.17	-10000	0	-0.37	70	70
PIK3C2B	-0.069	0.17	-10000	0	-0.4	78	78
CBL/CRKL	-0.049	0.16	0.27	1	-0.38	72	73
FER	-0.068	0.17	-10000	0	-0.41	79	79
SH2B3	-0.067	0.17	-10000	0	-0.4	80	80
PDPK1	-0.051	0.15	0.37	1	-0.35	63	64
SNAI2	-0.069	0.17	-10000	0	-0.41	69	69
positive regulation of cell proliferation	-0.13	0.29	-10000	0	-0.7	81	81
KITLG	0.015	0.034	-10000	0	-0.38	1	1
cell motility	-0.13	0.29	-10000	0	-0.7	81	81
PTPN6	0.028	0.021	-10000	0	-0.33	1	1
EPOR	-0.067	0.23	-10000	0	-0.88	18	18
STAT5A (dimer)	-0.1	0.24	-10000	0	-0.58	81	81
SOCS1	0.021	0.047	-10000	0	-0.36	6	6
cell migration	0.073	0.18	0.41	82	-10000	0	82
SOS1	0.028	0.003	-10000	0	-10000	0	0
EPO	0.004	0.058	-10000	0	-0.36	9	9
VAV1	0.022	0.043	-10000	0	-0.36	5	5
GRB10	-0.068	0.17	-10000	0	-0.41	72	72
PTPN11	0.029	0.008	-10000	0	-10000	0	0
SCF/KIT	-0.072	0.18	-10000	0	-0.42	81	81
GO:0007205	0.003	0.009	-10000	0	-10000	0	0
MAP2K1	-0.031	0.1	0.23	3	-0.29	14	17
CBL	0.027	0.006	-10000	0	-10000	0	0
KIT	-0.22	0.48	-10000	0	-1.1	89	89
MAP2K2	-0.031	0.1	0.23	3	-0.29	14	17
SHC/Grb2/SOS1	-0.034	0.18	-10000	0	-0.39	71	71
STAT5A	-0.1	0.25	-10000	0	-0.59	81	81
GRB2	0.027	0.005	-10000	0	-10000	0	0
response to radiation	-0.068	0.16	-10000	0	-0.4	70	70
SHC/GRAP2	0.031	0.051	-10000	0	-0.27	11	11
PTPRO	-0.092	0.18	-10000	0	-0.43	80	80
SH2B2	-0.07	0.17	-10000	0	-0.41	71	71
DOK1	0.027	0.019	-10000	0	-0.35	1	1
MATK	-0.074	0.18	-10000	0	-0.42	82	82
CREBBP	0.013	0.057	-10000	0	-10000	0	0
BCL2	-0.12	0.32	-10000	0	-0.94	39	39

×

HIF-1-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
PKM2	-0.33	0.33	-10000	0	-0.84	76	76
HDAC7	0.026	0.012	-10000	0	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.26	0.33	-10000	0	-0.92	45	45
SMAD4	0.025	0.01	-10000	0	-10000	0	0
ID2	-0.32	0.34	0.41	1	-0.87	65	66
AP1	0.024	0.07	-10000	0	-0.27	21	21
ABCG2	-0.33	0.34	0.41	1	-0.9	62	63
HIF1A	-0.063	0.065	-10000	0	-0.25	1	1
TFF3	-0.38	0.37	0.41	1	-0.91	85	86
GATA2	0.023	0.046	-10000	0	-0.38	5	5
AKT1	-0.066	0.076	-10000	0	-0.26	3	3
response to hypoxia	-0.069	0.066	-10000	0	-0.22	27	27
MCL1	-0.32	0.33	-10000	0	-0.89	60	60
NDRG1	-0.31	0.33	0.41	1	-0.88	60	61
SERPINE1	-0.34	0.34	0.41	1	-0.89	67	68
FECH	-0.32	0.33	0.41	1	-0.88	64	65
FURIN	-0.32	0.33	0.41	1	-0.88	60	61
NCOA2	0.024	0.023	-10000	0	-0.38	1	1
EP300	-0.064	0.1	-10000	0	-0.35	29	29
HMOX1	-0.32	0.34	0.41	1	-0.88	64	65
BHLHE40	-0.32	0.34	0.41	1	-0.88	63	64
BHLHE41	-0.32	0.33	-10000	0	-0.9	58	58
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.034	0.098	-10000	0	-10000	0	0
ENG	-0.043	0.082	0.31	2	-10000	0	2
JUN	0.028	0.006	-10000	0	-10000	0	0
RORA	-0.32	0.34	0.41	1	-0.88	65	66
ABCB1	-0.1	0.2	-10000	0	-0.9	20	20
TFRC	-0.32	0.33	0.41	1	-0.88	64	65
CXCR4	-0.33	0.34	0.41	1	-0.88	67	68
TF	-0.38	0.37	0.41	1	-0.91	87	88
CITED2	-0.32	0.34	0.41	1	-0.88	64	65
HIF1A/ARNT	-0.34	0.39	-10000	0	-0.97	65	65
LDHA	-0.039	0.11	-10000	0	-0.74	7	7
ETS1	-0.32	0.34	0.41	1	-0.87	65	66
PGK1	-0.32	0.34	0.41	1	-0.88	65	66
NOS2	-0.38	0.36	0.41	1	-0.92	82	83
ITGB2	-0.32	0.34	0.41	1	-0.88	65	66
ALDOA	-0.32	0.34	0.41	1	-0.88	64	65
Cbp/p300/CITED2	-0.33	0.37	-10000	0	-1	58	58
FOS	0.006	0.091	-10000	0	-0.38	21	21
HK2	-0.33	0.34	0.41	1	-0.89	66	67
SP1	0.027	0.026	-10000	0	-10000	0	0
GCK	-0.13	0.31	-10000	0	-1.3	24	24
HK1	-0.32	0.33	0.41	1	-0.88	64	65
NPM1	-0.32	0.33	0.41	1	-0.88	64	65
EGLN1	-0.32	0.33	-10000	0	-0.9	58	58
CREB1	0.032	0.004	-10000	0	-10000	0	0
PGM1	-0.32	0.34	0.41	1	-0.88	65	66
SMAD3	0.028	0.005	-10000	0	-10000	0	0
EDN1	-0.082	0.17	-10000	0	-0.74	12	12
IGFBP1	-0.37	0.36	0.41	1	-0.92	76	77
VEGFA	-0.23	0.27	0.37	1	-0.79	41	42
HIF1A/JAB1	-0.024	0.054	-10000	0	-10000	0	0
CP	-0.35	0.35	0.41	1	-0.92	70	71
CXCL12	-0.33	0.34	0.41	1	-0.88	72	73
COPS5	0.025	0.01	-10000	0	-10000	0	0
SMAD3/SMAD4	0.036	0.016	-10000	0	-10000	0	0
BNIP3	-0.32	0.34	0.41	1	-0.88	66	67
EGLN3	-0.32	0.33	0.41	1	-0.88	64	65
CA9	-0.37	0.36	0.41	1	-0.89	86	87
TERT	-0.35	0.35	0.41	1	-0.91	72	73
ENO1	-0.32	0.33	0.41	1	-0.87	65	66
PFKL	-0.32	0.34	0.41	1	-0.88	65	66
NCOA1	0.028	0.003	-10000	0	-10000	0	0
ADM	-0.32	0.34	0.41	1	-0.87	67	68
ARNT	-0.058	0.062	-10000	0	-10000	0	0
HNF4A	0.01	0.063	-10000	0	-0.38	9	9
ADFP	-0.33	0.33	-10000	0	-0.84	76	76
SLC2A1	-0.25	0.29	0.37	1	-0.82	48	49
LEP	-0.34	0.35	0.41	1	-0.9	71	72
HIF1A/ARNT/Cbp/p300	-0.28	0.34	-10000	0	-0.93	48	48
EPO	-0.17	0.2	-10000	0	-0.74	11	11
CREBBP	-0.068	0.11	-10000	0	-0.34	36	36
HIF1A/ARNT/Cbp/p300/HDAC7	-0.26	0.34	-10000	0	-0.95	43	43
PFKFB3	-0.32	0.33	0.41	1	-0.87	62	63
NT5E	-0.32	0.34	0.41	1	-0.89	65	66

×

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	-0.08	0.14	-9999	-0.38	51	51
FZD6	0.022	0.03	-9999	-0.38	2	2
WNT6	-0.031	0.14	-9999	-0.38	59	59
WNT4	-0.036	0.15	-9999	-0.38	62	62
FZD3	0.024	0.022	-9999	-0.38	1	1
WNT5A	-0.004	0.1	-9999	-0.35	34	34
WNT11	-0.068	0.17	-9999	-0.36	101	101

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.039	0.17	-10000	0	-0.54	27	27
IHH	-0.028	0.15	-10000	0	-0.43	48	48
SHH Np/Cholesterol/GAS1	-0.017	0.095	-10000	0	-0.22	71	71
LRPAP1	0.026	0.007	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.017	0.094	0.22	71	-10000	0	71
SMO/beta Arrestin2	-0.027	0.16	-10000	0	-0.5	26	26
SMO	-0.042	0.16	-10000	0	-0.51	27	27
AKT1	-0.025	0.15	-10000	0	-0.53	21	21
ARRB2	0.026	0.007	-10000	0	-10000	0	0
BOC	-0.014	0.12	-10000	0	-0.38	41	41
ADRBK1	0.027	0.006	-10000	0	-10000	0	0
heart looping	-0.039	0.16	-10000	0	-0.5	27	27
STIL	-0.056	0.14	-10000	0	-0.38	40	40
DHH N/PTCH2	-0.005	0.11	-10000	0	-0.25	64	64
DHH N/PTCH1	-0.016	0.13	-10000	0	-0.38	31	31
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
DHH	0.016	0.067	-10000	0	-0.38	11	11
PTHLH	-0.062	0.23	-10000	0	-0.76	32	32
determination of left/right symmetry	-0.039	0.16	-10000	0	-0.5	27	27
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
skeletal system development	-0.061	0.23	-10000	0	-0.75	32	32
IHH N/Hhip	-0.067	0.17	-10000	0	-0.34	113	113
DHH N/Hhip	-0.039	0.14	-10000	0	-0.28	99	99
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.039	0.16	-10000	0	-0.5	27	27
pancreas development	-0.067	0.17	-10000	0	-0.38	94	94
HHAT	0.021	0.05	-10000	0	-0.38	6	6
PI3K	0.036	0.014	-10000	0	-10000	0	0
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.021	0.13	-10000	0	-0.38	48	48
somite specification	-0.039	0.16	-10000	0	-0.5	27	27
SHH Np/Cholesterol/PTCH1	-0.031	0.12	-10000	0	-0.4	23	23
SHH Np/Cholesterol/PTCH2	-0.022	0.094	-10000	0	-0.2	85	85
SHH Np/Cholesterol/Megalin	-0.019	0.092	-10000	0	-0.2	79	79
SHH	-0.012	0.082	-10000	0	-0.28	34	34
catabolic process	-0.026	0.14	-10000	0	-0.41	27	27
SMO/Vitamin D3	-0.038	0.15	-10000	0	-0.46	25	25
SHH Np/Cholesterol/Hhip	-0.043	0.12	-10000	0	-0.24	105	105
LRP2	-0.025	0.13	-10000	0	-0.35	55	55
receptor-mediated endocytosis	-0.052	0.14	-10000	0	-0.44	28	28
SHH Np/Cholesterol/BOC	-0.013	0.093	-10000	0	-0.22	65	65
SHH Np/Cholesterol/CDO	0.001	0.072	-10000	0	-0.21	41	41
mesenchymal cell differentiation	0.043	0.12	0.24	105	-10000	0	105
mol:Vitamin D3	-0.029	0.13	-10000	0	-0.4	23	23
IHH N/PTCH2	-0.037	0.14	-10000	0	-0.27	99	99
CDON	0.018	0.058	-10000	0	-0.37	9	9
IHH N/PTCH1	-0.019	0.14	-10000	0	-0.42	27	27
Megalin/LRPAP1	0	0.096	-10000	0	-0.25	54	54
PTCH2	-0.022	0.13	-10000	0	-0.36	54	54
SHH Np/Cholesterol	-0.003	0.064	-10000	0	-0.21	34	34
PTCH1	-0.026	0.14	-10000	0	-0.41	27	27
HHIP	-0.067	0.17	-10000	0	-0.38	94	94

×

IL4-mediated signaling 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
BCL2L1	-0.48	0.44	-10000	0	-1.2	67	67
STAT6 (cleaved dimer)	-0.5	0.45	-10000	0	-1.2	89	89
IGHG1	-0.17	0.14	-10000	0	-10000	0	0
IGHG3	-0.48	0.42	-10000	0	-1.1	86	86
AKT1	-0.26	0.27	-10000	0	-0.92	35	35
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.2	0.27	-10000	0	-0.98	31	31
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.26	0.28	-10000	0	-0.99	27	27
THY1	-0.51	0.44	-10000	0	-1.2	81	81
MYB	-0.039	0.14	-10000	0	-0.35	71	71
HMGA1	0.026	0.02	-10000	0	-0.35	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.31	0.29	-10000	0	-0.87	45	45
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.26	0.28	-10000	0	-1	27	27
SP1	0.019	0.031	-10000	0	-10000	0	0
INPP5D	0.025	0.034	-10000	0	-0.36	3	3
SOCS5	0.04	0.019	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.49	0.45	-10000	0	-1.2	83	83
SOCS1	-0.34	0.28	-10000	0	-0.77	60	60
SOCS3	-0.26	0.24	-10000	0	-0.82	24	24
FCER2	-0.58	0.56	-10000	0	-1.4	111	111
PARP14	0.015	0.046	-10000	0	-0.35	5	5
CCL17	-0.53	0.48	-10000	0	-1.3	80	80
GRB2	0.027	0.005	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.21	0.21	-10000	0	-0.75	26	26
T cell proliferation	-0.49	0.45	-10000	0	-1.2	73	73
IL4R/JAK1	-0.5	0.44	-10000	0	-1.2	76	76
EGR2	-0.54	0.48	-10000	0	-1.3	79	79
JAK2	-0.03	0.038	-10000	0	-10000	0	0
JAK3	0.013	0.079	-10000	0	-0.35	18	18
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
JAK1	-0.003	0.024	-10000	0	-10000	0	0
COL1A2	-0.2	0.21	-10000	0	-0.87	12	12
CCL26	-0.52	0.45	-10000	0	-1.2	79	79
IL4R	-0.53	0.47	-10000	0	-1.3	72	72
PTPN6	0.037	0.024	-10000	0	-0.34	1	1
IL13RA2	-0.54	0.44	-10000	0	-1.2	82	82
IL13RA1	-0.032	0.039	-10000	0	-10000	0	0
IRF4	-0.16	0.3	-10000	0	-1.1	31	31
ARG1	-0.11	0.14	-10000	0	-0.81	4	4
CBL	-0.3	0.27	-10000	0	-0.82	43	43
GTF3A	0.001	0.041	-10000	0	-10000	0	0
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.037	0.051	-10000	0	-10000	0	0
IRF4/BCL6	-0.13	0.27	-10000	0	-1	28	28
CD40LG	0.007	0.078	-10000	0	-0.38	14	14
MAPK14	-0.29	0.27	-10000	0	-0.86	38	38
mitosis	-0.24	0.25	-10000	0	-0.84	35	35
STAT6	-0.57	0.53	-10000	0	-1.4	82	82
SPI1	0.027	0.03	-10000	0	-0.35	2	2
RPS6KB1	-0.24	0.24	-10000	0	-0.81	35	35
STAT6 (dimer)	-0.57	0.53	-10000	0	-1.4	82	82
STAT6 (dimer)/PARP14	-0.55	0.5	-10000	0	-1.3	87	87
mast cell activation	0.013	0.01	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.26	0.3	-10000	0	-1	34	34
FRAP1	-0.26	0.27	-10000	0	-0.91	35	35
LTA	-0.5	0.45	-10000	0	-1.3	71	71
FES	0.023	0.04	-10000	0	-0.38	4	4
T-helper 1 cell differentiation	0.55	0.5	1.3	82	-10000	0	82
CCL11	-0.53	0.49	-10000	0	-1.3	93	93
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.26	0.28	-10000	0	-0.96	33	33
IL2RG	0.022	0.06	-10000	0	-0.37	9	9
IL10	-0.5	0.44	-10000	0	-1.2	73	73
IRS1	0.027	0.021	-10000	0	-0.38	1	1
IRS2	0.012	0.074	-10000	0	-0.38	14	14
IL4	-0.17	0.26	-10000	0	-1.1	24	24
IL5	-0.5	0.44	-10000	0	-1.3	67	67
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.43	0.37	-10000	0	-1	77	77
COL1A1	-0.25	0.23	-10000	0	-0.82	14	14
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.51	0.46	-10000	0	-1.3	64	64
IL2R gamma/JAK3	0.02	0.074	-10000	0	-0.25	27	27
TFF3	-0.57	0.47	-10000	0	-1.3	93	93
ALOX15	-0.53	0.46	-10000	0	-1.3	77	77
MYBL1	0.015	0.062	-10000	0	-0.35	11	11
T-helper 2 cell differentiation	-0.44	0.38	-10000	0	-1	77	77
SHC1	0.027	0.005	-10000	0	-10000	0	0
CEBPB	0.023	0.016	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.25	0.26	-10000	0	-0.96	25	25
mol:PI-3-4-5-P3	-0.26	0.27	-10000	0	-0.91	35	35
PI3K	-0.27	0.3	-10000	0	-1	35	35
DOK2	0.023	0.03	-10000	0	-0.38	2	2
ETS1	0.037	0.02	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.2	0.19	-10000	0	-0.69	22	22
ITGB3	-0.5	0.44	-10000	0	-1.2	72	72
PIGR	-0.68	0.6	-10000	0	-1.4	154	154
IGHE	0.06	0.073	0.19	55	-10000	0	55
MAPKKK cascade	-0.19	0.19	-10000	0	-0.68	22	22
BCL6	0.029	0.01	-10000	0	-10000	0	0
OPRM1	-0.5	0.44	-10000	0	-1.2	75	75
RETNLB	-0.59	0.52	-10000	0	-1.3	101	101
SELP	-0.57	0.53	-10000	0	-1.4	90	90
AICDA	-0.49	0.43	-10000	0	-1.2	71	71

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.43	0.36	-10000	0	-1.1	60	60
IL23A	-0.44	0.37	-10000	0	-1.1	52	52
NF kappa B1 p50/RelA/I kappa B alpha	-0.44	0.36	-10000	0	-1	70	70
positive regulation of T cell mediated cytotoxicity	-0.47	0.4	-10000	0	-1.1	73	73
ITGA3	-0.42	0.35	-10000	0	-1.1	51	51
IL17F	-0.34	0.25	-10000	0	-0.72	71	71
IL12B	-0.034	0.049	-10000	0	-0.39	5	5
STAT1 (dimer)	-0.46	0.39	-10000	0	-1.1	72	72
CD4	-0.42	0.35	-10000	0	-1.1	54	54
IL23	-0.43	0.35	-10000	0	-1.1	50	50
IL23R	-0.11	0.25	-10000	0	-1.1	20	20
IL1B	-0.45	0.38	-10000	0	-1.2	58	58
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.46	0.36	-10000	0	-1	72	72
TYK2	-0.022	0.027	-10000	0	-10000	0	0
STAT4	0.024	0.038	-10000	0	-0.35	4	4
STAT3	0.027	0.007	-10000	0	-10000	0	0
IL18RAP	0.006	0.069	-10000	0	-0.38	12	12
IL12RB1	-0.026	0.046	-10000	0	-0.41	4	4
PIK3CA	0.025	0.008	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	-0.024	0.047	-10000	0	-0.3	4	4
IL23R/JAK2	-0.11	0.24	-10000	0	-1.1	18	18
positive regulation of chronic inflammatory response	-0.47	0.4	-10000	0	-1.1	73	73
natural killer cell activation	0.009	0.013	0.075	12	-10000	0	12
JAK2	-0.025	0.031	-10000	0	-10000	0	0
PIK3R1	0.025	0.009	-10000	0	-10000	0	0
NFKB1	0.024	0.005	-10000	0	-10000	0	0
RELA	0.024	0.005	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.41	0.34	-10000	0	-1	51	51
ALOX12B	-0.46	0.36	-10000	0	-1	70	70
CXCL1	-0.48	0.36	-10000	0	-1	75	75
T cell proliferation	-0.47	0.4	-10000	0	-1.1	73	73
NFKBIA	0.024	0.004	-10000	0	-10000	0	0
IL17A	-0.31	0.21	-10000	0	-0.58	92	92
PI3K	-0.44	0.37	-10000	0	-1.1	68	68
IFNG	-0.023	0.043	0.14	12	-0.12	9	21
STAT3 (dimer)	-0.44	0.37	-10000	0	-1.1	68	68
IL18R1	0.016	0.034	-10000	0	-0.37	2	2
IL23/IL23R/JAK2/TYK2/SOCS3	-0.27	0.24	-10000	0	-0.83	32	32
IL18/IL18R	0.025	0.069	-10000	0	-0.23	15	15
macrophage activation	-0.024	0.015	-10000	0	-0.045	30	30
TNF	-0.44	0.37	-10000	0	-1.2	50	50
STAT3/STAT4	-0.44	0.38	-10000	0	-1.1	71	71
STAT4 (dimer)	-0.45	0.39	-10000	0	-1.1	73	73
IL18	0.013	0.043	-10000	0	-0.36	4	4
IL19	-0.49	0.43	-10000	0	-1.2	86	86
STAT5A (dimer)	-0.45	0.39	-10000	0	-1.1	71	71
STAT1	0.018	0.059	-10000	0	-0.35	10	10
SOCS3	0.027	0.005	-10000	0	-10000	0	0
CXCL9	-0.47	0.36	-10000	0	-1	75	75
MPO	-0.43	0.35	-10000	0	-1	60	60
positive regulation of humoral immune response	-0.47	0.4	-10000	0	-1.1	73	73
IL23/IL23R/JAK2/TYK2	-0.48	0.43	-10000	0	-1.2	73	73
IL6	-0.46	0.41	-10000	0	-1.2	73	73
STAT5A	0.028	0.004	-10000	0	-10000	0	0
IL2	0.013	0.035	-10000	0	-0.35	2	2
positive regulation of tyrosine phosphorylation of STAT protein	0.009	0.013	0.075	12	-10000	0	12
CD3E	-0.42	0.35	-10000	0	-1.1	55	55
keratinocyte proliferation	-0.47	0.4	-10000	0	-1.1	73	73
NOS2	-0.48	0.37	-10000	0	-1	88	88

×

Syndecan-1-mediated signaling events

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.027	0.006	-10000	0	-10000	0	0
CCL5	0.019	0.059	-10000	0	-0.38	9	9
SDCBP	0.025	0.009	-10000	0	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.079	0.12	0.24	8	-0.31	43	51
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
Syndecan-1/Laminin-5	-0.076	0.11	0.23	3	-0.3	42	45
Syndecan-1/Syntenin	-0.069	0.12	0.25	6	-0.29	41	47
MAPK3	-0.072	0.11	0.21	5	-0.29	33	38
HGF/MET	0.014	0.082	-10000	0	-0.26	33	33
TGFB1/TGF beta receptor Type II	0.027	0.006	-10000	0	-10000	0	0
BSG	0.027	0.006	-10000	0	-10000	0	0
keratinocyte migration	-0.076	0.11	0.22	3	-0.3	42	45
Syndecan-1/RANTES	-0.075	0.12	0.24	8	-0.3	44	52
Syndecan-1/CD147	-0.065	0.12	0.24	8	-0.29	39	47
Syndecan-1/Syntenin/PIP2	-0.068	0.11	0.24	6	-0.28	41	47
LAMA5	0.022	0.022	-10000	0	-0.35	1	1
positive regulation of cell-cell adhesion	-0.067	0.11	0.23	6	-0.27	41	47
MMP7	-0.15	0.19	-10000	0	-0.35	193	193
HGF	0.014	0.07	-10000	0	-0.37	13	13
Syndecan-1/CASK	-0.084	0.11	-10000	0	-0.29	44	44
Syndecan-1/HGF/MET	-0.078	0.13	0.31	3	-0.36	23	26
regulation of cell adhesion	-0.07	0.11	0.23	8	-0.34	15	23
HPSE	0.016	0.065	-10000	0	-0.36	12	12
positive regulation of cell migration	-0.079	0.12	0.24	8	-0.31	43	51
SDC1	-0.083	0.12	0.18	1	-0.31	44	45
Syndecan-1/Collagen	-0.079	0.12	0.24	8	-0.31	43	51
PPIB	0.027	0.005	-10000	0	-10000	0	0
MET	0.005	0.088	-10000	0	-0.36	23	23
PRKACA	0.027	0.005	-10000	0	-10000	0	0
MMP9	-0.062	0.16	-10000	0	-0.35	92	92
MAPK1	-0.068	0.11	0.22	8	-0.29	33	41
homophilic cell adhesion	-0.078	0.12	0.26	9	-0.31	43	52
MMP1	-0.13	0.19	-10000	0	-0.36	165	165

×

Glypican 2 network

Figure S14. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S14. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	0.012	0.074	-9999	-0.36	16	16
GPC2	-0.006	0.1	-9999	-0.35	34	34
GPC2/Midkine	0.002	0.095	-9999	-0.25	49	49
neuron projection morphogenesis	0.002	0.094	-9999	-0.25	49	49

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	0.019	0.036	-10000	0	-0.38	3	3
GNB1/GNG2	-0.06	0.15	-10000	0	-0.36	50	50
mol:DAG	-0.059	0.13	0.21	7	-0.34	42	49
PLCG1	-0.061	0.13	0.21	7	-0.35	42	49
YES1	-0.078	0.14	-10000	0	-0.37	49	49
FZD3	0.024	0.022	-10000	0	-0.38	1	1
FZD6	0.022	0.03	-10000	0	-0.38	2	2
G protein	-0.034	0.16	0.26	8	-0.36	40	48
MAP3K7	-0.062	0.12	0.2	11	-0.34	32	43
mol:Ca2+	-0.057	0.13	0.21	7	-0.33	42	49
mol:IP3	-0.059	0.13	0.21	7	-0.34	42	49
NLK	0.007	0.047	-10000	0	-0.91	1	1
GNB1	0.026	0.007	-10000	0	-10000	0	0
CAMK2A	-0.064	0.13	0.21	11	-0.32	46	57
MAP3K7IP1	0	0	-10000	0	-10000	0	0
Noncanonical Wnts/FZD	-0.08	0.14	-10000	0	-0.38	51	51
CSNK1A1	0.027	0.006	-10000	0	-10000	0	0
GNAS	-0.07	0.13	0.18	1	-0.37	43	44
GO:0007205	-0.059	0.13	0.23	10	-0.34	43	53
WNT6	-0.031	0.14	-10000	0	-0.38	59	59
WNT4	-0.036	0.15	-10000	0	-0.38	62	62
NFAT1/CK1 alpha	-0.051	0.14	0.33	3	-0.4	27	30
GNG2	0.027	0.019	-10000	0	-0.35	1	1
WNT5A	-0.004	0.1	-10000	0	-0.35	34	34
WNT11	-0.068	0.17	-10000	0	-0.36	101	101
CDC42	-0.07	0.13	0.19	4	-0.36	47	51

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.026	0.007	-10000	0	-10000	0	0
LAT2	-0.07	0.13	-10000	0	-0.34	52	52
AP1	-0.06	0.17	0.26	2	-0.4	53	55
mol:PIP3	-0.084	0.16	0.3	9	-0.4	45	54
IKBKB	-0.043	0.11	0.22	17	-0.24	43	60
AKT1	-0.069	0.13	0.36	10	-0.31	24	34
IKBKG	-0.047	0.11	0.22	14	-0.24	47	61
MS4A2	-0.036	0.15	-10000	0	-0.39	62	62
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
MAP3K1	-0.054	0.13	0.29	11	-0.33	43	54
mol:Ca2+	-0.064	0.13	0.26	10	-0.31	45	55
LYN	0.024	0.01	-10000	0	-10000	0	0
CBLB	-0.07	0.13	-10000	0	-0.34	51	51
SHC1	0.027	0.005	-10000	0	-10000	0	0
RasGAP/p62DOK	0.042	0.043	-10000	0	-0.2	10	10
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	0.025	0.034	-10000	0	-0.36	3	3
PLD2	-0.085	0.13	0.28	13	-0.34	44	57
PTPN13	-0.074	0.16	0.36	1	-0.49	20	21
PTPN11	0.012	0.026	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	-0.055	0.12	0.32	8	-0.28	25	33
SYK	0.025	0.022	-10000	0	-0.4	1	1
GRB2	0.027	0.005	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.079	0.16	0.17	1	-0.4	50	51
LAT	-0.07	0.13	-10000	0	-0.34	55	55
PAK2	-0.059	0.15	0.28	14	-0.36	47	61
NFATC2	-0.025	0.066	-10000	0	-0.58	3	3
HRAS	-0.071	0.15	0.27	7	-0.38	51	58
GAB2	0.027	0.006	-10000	0	-10000	0	0
PLA2G1B	0.007	0.1	-10000	0	-0.87	5	5
Fc epsilon R1	-0.085	0.18	-10000	0	-0.29	166	166
Antigen/IgE/Fc epsilon R1	-0.075	0.16	-10000	0	-0.26	166	166
mol:GDP	-0.074	0.15	0.23	1	-0.39	53	54
JUN	0.028	0.004	-10000	0	-10000	0	0
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
FOS	0.006	0.091	-10000	0	-0.38	21	21
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.072	0.14	-10000	0	-0.33	65	65
CHUK	-0.051	0.1	0.22	11	-0.24	48	59
KLRG1	-0.068	0.12	-10000	0	-0.31	53	53
VAV1	-0.07	0.13	-10000	0	-0.34	55	55
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.068	0.13	-10000	0	-0.33	54	54
negative regulation of mast cell degranulation	-0.057	0.12	0.18	3	-0.3	48	51
BTK	-0.076	0.16	0.23	1	-0.41	54	55
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.11	0.18	-10000	0	-0.44	66	66
GAB2/PI3K/SHP2	-0.088	0.1	-10000	0	-0.32	37	37
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.077	0.14	-10000	0	-0.36	55	55
RAF1	0.025	0.11	-10000	0	-0.94	5	5
Fc epsilon R1/FcgammaRIIB/SHIP	-0.061	0.17	-10000	0	-0.27	148	148
FCER1G	0.02	0.057	-10000	0	-0.36	9	9
FCER1A	-0.12	0.2	-10000	0	-0.4	147	147
Antigen/IgE/Fc epsilon R1/Fyn	-0.061	0.15	-10000	0	-0.24	161	161
MAPK3	0.021	0.099	-10000	0	-0.83	5	5
MAPK1	0.019	0.1	-10000	0	-0.87	5	5
NFKB1	0.027	0.005	-10000	0	-10000	0	0
MAPK8	-0.058	0.22	-10000	0	-0.63	43	43
DUSP1	0.017	0.064	-10000	0	-0.38	10	10
NF-kappa-B/RelA	-0.024	0.066	-10000	0	-0.19	6	6
actin cytoskeleton reorganization	-0.069	0.16	0.37	1	-0.47	21	22
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.056	0.14	0.23	1	-0.36	42	43
FER	-0.065	0.13	-10000	0	-0.34	53	53
RELA	0.027	0.005	-10000	0	-10000	0	0
ITK	-0.025	0.061	-10000	0	-0.24	18	18
SOS1	0.028	0.003	-10000	0	-10000	0	0
PLCG1	-0.055	0.16	0.26	10	-0.39	45	55
cytokine secretion	-0.02	0.046	-10000	0	-10000	0	0
SPHK1	-0.077	0.14	-10000	0	-0.34	64	64
PTK2	-0.072	0.16	0.37	1	-0.5	19	20
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.078	0.17	0.19	2	-0.41	49	51
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	-0.083	0.16	0.28	9	-0.4	48	57
MAP2K2	0.016	0.1	-10000	0	-0.87	5	5
MAP2K1	0.019	0.099	-10000	0	-0.84	5	5
MAP2K7	0.027	0.006	-10000	0	-10000	0	0
KLRG1/SHP2	-0.057	0.12	0.19	3	-0.3	42	45
MAP2K4	-0.091	0.33	-10000	0	-0.92	55	55
Fc epsilon R1/FcgammaRIIB	-0.072	0.18	-10000	0	-0.27	169	169
mol:Choline	-0.084	0.13	0.28	13	-0.34	44	57
SHC/Grb2/SOS1	-0.04	0.15	0.24	1	-0.34	44	45
FYN	0.027	0.005	-10000	0	-10000	0	0
DOK1	0.027	0.019	-10000	0	-0.35	1	1
PXN	-0.067	0.15	0.36	1	-0.46	19	20
HCLS1	-0.07	0.13	-10000	0	-0.34	51	51
PRKCB	-0.071	0.14	0.25	10	-0.32	58	68
FCGR2B	0.012	0.077	-10000	0	-0.38	15	15
IGHE	-0.002	0.005	-10000	0	-10000	0	0
KLRG1/SHIP	-0.058	0.13	0.18	3	-0.31	48	51
LCP2	0.027	0.006	-10000	0	-10000	0	0
PLA2G4A	-0.076	0.14	-10000	0	-0.34	60	60
RASA1	0.025	0.008	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.084	0.13	0.28	13	-0.34	44	57
IKK complex	-0.028	0.09	0.21	20	-0.21	8	28
WIPF1	0.027	0.021	-10000	0	-0.38	1	1

×

EPHB forward signaling

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
Ephrin A5/EPHB2	-0.092	0.13	-10000	0	-0.22	205	205
cell-cell adhesion	0.097	0.1	0.3	55	-10000	0	55
Ephrin B/EPHB2/RasGAP	-0.053	0.13	-10000	0	-0.35	9	9
ITSN1	0.027	0.006	-10000	0	-10000	0	0
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
SHC1	0.027	0.005	-10000	0	-10000	0	0
Ephrin B1/EPHB3	0.029	0.04	-10000	0	-0.23	9	9
Ephrin B1/EPHB1	-0.009	0.094	-10000	0	-0.2	77	77
HRAS/GDP	-0.023	0.11	-10000	0	-0.29	19	19
Ephrin B/EPHB1/GRB7	0.01	0.1	-10000	0	-0.35	3	3
Endophilin/SYNJ1	-0.076	0.097	0.17	12	-0.33	9	21
KRAS	0.025	0.009	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	0.014	0.1	-10000	0	-0.24	11	11
endothelial cell migration	0.046	0.026	-10000	0	-10000	0	0
GRB2	0.027	0.005	-10000	0	-10000	0	0
GRB7	0.019	0.044	-10000	0	-0.37	5	5
PAK1	-0.075	0.1	0.18	15	-0.34	8	23
HRAS	0.026	0.007	-10000	0	-10000	0	0
RRAS	-0.079	0.097	0.17	8	-0.36	8	16
DNM1	0.016	0.064	-10000	0	-0.35	12	12
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.029	0.091	0.21	23	-0.34	3	26
lamellipodium assembly	-0.097	0.1	-10000	0	-0.3	55	55
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.002	0.064	-10000	0	-0.28	2	2
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
EPHB2	-0.16	0.19	-10000	0	-0.35	204	204
EPHB3	0.017	0.06	-10000	0	-0.38	9	9
EPHB1	-0.044	0.15	-10000	0	-0.35	77	77
EPHB4	0.026	0.008	-10000	0	-10000	0	0
mol:GDP	-0.046	0.093	0.24	2	-0.3	17	19
Ephrin B/EPHB2	-0.058	0.12	-10000	0	-0.19	174	174
Ephrin B/EPHB3	0.039	0.062	-10000	0	-0.19	23	23
JNK cascade	-0.11	0.13	0.3	9	-0.33	57	66
Ephrin B/EPHB1	0.006	0.099	-10000	0	-0.19	76	76
RAP1/GDP	-0.034	0.1	0.23	8	-0.3	12	20
EFNB2	0.026	0.008	-10000	0	-10000	0	0
EFNB3	0.008	0.083	-10000	0	-0.38	18	18
EFNB1	0.027	0.005	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.092	0.14	-10000	0	-0.23	203	203
RAP1B	0.027	0.007	-10000	0	-10000	0	0
RAP1A	0.027	0.005	-10000	0	-10000	0	0
CDC42/GTP	-0.078	0.13	-10000	0	-0.3	59	59
Rap1/GTP	-0.086	0.12	-10000	0	-0.3	61	61
axon guidance	-0.092	0.13	-10000	0	-0.22	205	205
MAPK3	-0.004	0.056	0.19	1	-0.26	2	3
MAPK1	-0.004	0.058	0.19	2	-0.26	2	4
Rac1/GDP	-0.042	0.097	0.23	4	-0.28	16	20
actin cytoskeleton reorganization	-0.078	0.097	-10000	0	-0.26	54	54
CDC42/GDP	-0.038	0.1	0.23	9	-0.28	18	27
PI3K	0.051	0.029	-10000	0	-10000	0	0
EFNA5	0.008	0.084	-10000	0	-0.38	18	18
Ephrin B2/EPHB4	0.032	0.014	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	-0.04	0.078	-10000	0	-0.29	11	11
CDC42	0.026	0.007	-10000	0	-10000	0	0
RAS family/GTP	-0.082	0.12	-10000	0	-0.29	58	58
PTK2	0.11	0.23	0.66	61	-10000	0	61
MAP4K4	-0.11	0.14	0.3	9	-0.34	57	66
SRC	0.024	0.01	-10000	0	-10000	0	0
KALRN	0.022	0.045	-10000	0	-0.38	5	5
Intersectin/N-WASP	0.038	0.012	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.057	0.12	0.28	15	-0.31	8	23
MAP2K1	-0.003	0.058	-10000	0	-0.26	2	2
WASL	0.027	0.006	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.094	0.16	-10000	0	-0.24	208	208
cell migration	0.004	0.09	0.25	9	-0.3	4	13
NRAS	0.027	0.005	-10000	0	-10000	0	0
SYNJ1	-0.077	0.098	0.17	12	-0.33	9	21
PXN	0.027	0.005	-10000	0	-10000	0	0
TF	-0.14	0.12	0.17	3	-0.34	74	77
HRAS/GTP	-0.081	0.13	-10000	0	-0.31	61	61
Ephrin B1/EPHB1-2	-0.1	0.15	-10000	0	-0.23	216	216
cell adhesion mediated by integrin	0.004	0.061	0.2	10	-0.2	18	28
RAC1	0.026	0.008	-10000	0	-10000	0	0
mol:GTP	-0.084	0.14	-10000	0	-0.32	61	61
RAC1-CDC42/GTP	-0.091	0.12	-10000	0	-0.3	58	58
RASA1	0.025	0.008	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.036	0.099	0.23	4	-0.3	8	12
ruffle organization	-0.073	0.15	0.37	14	-0.3	52	66
NCK1	0.027	0.005	-10000	0	-10000	0	0
receptor internalization	-0.078	0.1	0.17	7	-0.33	16	23
Ephrin B/EPHB2/KALRN	-0.056	0.13	-10000	0	-0.35	10	10
ROCK1	0.021	0.054	0.18	28	-0.21	9	37
RAS family/GDP	-0.084	0.087	-10000	0	-0.25	48	48
Rac1/GTP	-0.089	0.12	-10000	0	-0.31	55	55
Ephrin B/EPHB1/Src/Paxillin	-0.003	0.06	-10000	0	-0.27	4	4

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	0.045	0.024	-10000	0	-0.18	3	3
RGS9BP	-0.011	0.12	-10000	0	-0.38	37	37
mol:GTP	0	0	-10000	0	-10000	0	0
GRK1	0.015	0.041	-10000	0	-0.35	5	5
mol:Na +	-0.052	0.12	-10000	0	-0.22	132	132
mol:ADP	-0.016	0.04	-10000	0	-0.25	11	11
GNAT2	0.027	0.005	-10000	0	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.023	0.13	-10000	0	-0.25	101	101
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.029	0.022	-10000	0	-0.2	3	3
GRK7	0.019	0.046	-10000	0	-0.35	6	6
CNGB3	-0.065	0.16	-10000	0	-0.35	95	95
Cone Metarhodopsin II/X-Arrestin	0.015	0.019	-10000	0	-0.24	2	2
mol:Ca2+	-0.055	0.12	0.18	35	-0.22	123	158
Cone PDE6	-0.007	0.13	-10000	0	-0.22	84	84
Cone Metarhodopsin II	0.021	0.036	-10000	0	-0.18	11	11
Na + (4 Units)	-0.048	0.12	-10000	0	-0.21	141	141
GNAT2/GDP	-0.009	0.12	-10000	0	-0.21	98	98
GNB5	0.027	0.005	-10000	0	-10000	0	0
mol:GMP (4 units)	-0.007	0.035	0.18	8	-0.24	3	11
Cone Transducin	0.048	0.025	-10000	0	-0.19	3	3
SLC24A2	0.003	0.085	-10000	0	-0.35	22	22
GNB3/GNGT2	0.037	0.028	-10000	0	-0.26	3	3
GNB3	0.024	0.035	-10000	0	-0.38	3	3
GNAT2/GTP	0.02	0.003	-10000	0	-10000	0	0
CNGA3	-0.027	0.14	-10000	0	-0.38	54	54
ARR3	0.02	0.027	-10000	0	-0.35	2	2
absorption of light	0	0	-10000	0	-10000	0	0
cGMP/Cone CNG Channel	-0.052	0.12	-10000	0	-0.22	132	132
mol:Pi	-0.024	0.13	-10000	0	-0.25	101	101
Cone CNG Channel	-0.029	0.11	-10000	0	-0.23	32	32
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	0.003	0.085	-10000	0	-0.35	22	22
RGS9	-0.058	0.17	-10000	0	-0.38	85	85
PDE6C	0.022	0.02	-10000	0	-0.35	1	1
GNGT2	0.028	0.002	-10000	0	-10000	0	0
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	0.017	0.032	-10000	0	-0.35	3	3

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	0.035	0.064	-10000	0	-0.23	20	20
fibroblast growth factor receptor signaling pathway	0.034	0.064	-10000	0	-0.23	20	20
LAMA1	-0.044	0.15	-10000	0	-0.36	76	76
PRNP	0.024	0.022	-10000	0	-0.38	1	1
GPC1/SLIT2	-0.014	0.12	-10000	0	-0.27	71	71
SMAD2	0.012	0.027	0.18	3	-0.19	4	7
GPC1/PrPc/Cu2+	0.03	0.03	-10000	0	-0.21	5	5
GPC1/Laminin alpha1	-0.017	0.12	-10000	0	-0.25	78	78
TDGF1	-0.035	0.14	-10000	0	-0.37	65	65
CRIPTO/GPC1	-0.01	0.11	-10000	0	-0.26	68	68
APP/GPC1	0.034	0.031	-10000	0	-0.25	4	4
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.022	0.084	-10000	0	-0.22	63	63
FLT1	0.025	0.02	-10000	0	-0.35	1	1
GPC1/TGFB/TGFBR1/TGFBR2	0.049	0.033	-10000	0	-0.2	5	5
SERPINC1	0.017	0.053	-10000	0	-0.35	8	8
FYN	-0.022	0.086	-10000	0	-0.22	65	65
FGR	-0.023	0.086	-10000	0	-0.22	66	66
positive regulation of MAPKKK cascade	-0.015	0.13	0.22	23	-0.33	30	53
SLIT2	-0.041	0.15	-10000	0	-0.38	68	68
GPC1/NRG	-0.027	0.12	-10000	0	-0.27	84	84
NRG1	-0.056	0.16	-10000	0	-0.38	81	81
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.046	0.033	-10000	0	-0.21	4	4
LYN	-0.018	0.08	-10000	0	-0.22	55	55
mol:Spermine	0.005	0.025	-10000	0	-0.24	4	4
cell growth	0.034	0.064	-10000	0	-0.23	20	20
BMP signaling pathway	-0.024	0.038	0.35	4	-10000	0	4
SRC	-0.015	0.076	-10000	0	-0.22	47	47
TGFBR1	0.026	0.019	-10000	0	-0.35	1	1
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.12	0.19	-10000	0	-0.36	157	157
GPC1	0.024	0.038	-10000	0	-0.35	4	4
TGFBR1 (dimer)	0.026	0.019	-10000	0	-0.35	1	1
VEGFA	0.025	0.02	-10000	0	-0.35	1	1
BLK	-0.056	0.12	-10000	0	-0.25	105	105
HCK	-0.014	0.076	-10000	0	-0.22	47	47
FGF2	0.009	0.084	-10000	0	-0.38	18	18
FGFR1	0.022	0.035	-10000	0	-0.38	3	3
VEGFR1 homodimer	0.025	0.02	-10000	0	-0.35	1	1
TGFBR2	0.027	0.005	-10000	0	-10000	0	0
cell death	0.034	0.031	-10000	0	-0.25	4	4
ATIII/GPC1	0.029	0.049	-10000	0	-0.25	12	12
PLA2G2A/GPC1	-0.075	0.14	-10000	0	-0.26	157	157
LCK	-0.029	0.092	-10000	0	-0.22	76	76
neuron differentiation	-0.027	0.12	-10000	0	-0.27	84	84
PrPc/Cu2+	0.018	0.016	-10000	0	-0.27	1	1
APP	0.026	0.008	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.027	0.005	-10000	0	-10000	0	0

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.003	0.069	-10000	0	-0.2	41	41
EPHB2	-0.16	0.19	-10000	0	-0.35	204	204
Syndecan-2/TACI	-0.025	0.097	-10000	0	-0.22	78	78
LAMA1	-0.044	0.15	-10000	0	-0.36	76	76
Syndecan-2/alpha2 ITGB1	0.03	0.065	-10000	0	-0.25	7	7
HRAS	0.026	0.007	-10000	0	-10000	0	0
Syndecan-2/CASK	0.007	0.015	-10000	0	-0.21	2	2
ITGA5	0.021	0.049	-10000	0	-0.35	7	7
BAX	0.004	0.01	-10000	0	-10000	0	0
EPB41	0.027	0.006	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	0.022	0.018	-10000	0	-0.19	2	2
LAMA3	0.014	0.066	-10000	0	-0.36	12	12
EZR	0.027	0.006	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	0.024	0.027	-10000	0	-0.35	2	2
Syndecan-2/MMP2	0.022	0.026	-10000	0	-0.21	4	4
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.025	0.059	-10000	0	-0.24	18	18
dendrite morphogenesis	-0.067	0.11	-10000	0	-0.2	168	168
Syndecan-2/GM-CSF	-0.025	0.093	-10000	0	-0.2	89	89
determination of left/right symmetry	0.009	0.019	-10000	0	-0.25	2	2
Syndecan-2/PKC delta	0.024	0.02	-10000	0	-0.21	2	2
GNB2L1	0.027	0.005	-10000	0	-10000	0	0
MAPK3	-0.012	0.1	0.19	36	-0.18	85	121
MAPK1	-0.014	0.099	0.19	33	-0.18	83	116
Syndecan-2/RACK1	0.034	0.023	-10000	0	-0.18	2	2
NF1	0.028	0.004	-10000	0	-10000	0	0
FGFR/FGF/Syndecan-2	0.009	0.019	-10000	0	-0.25	2	2
ITGA2	0.008	0.082	-10000	0	-0.35	20	20
MAPK8	0.008	0.015	-10000	0	-0.22	1	1
Syndecan-2/alpha2/beta1 Integrin	0.008	0.089	-10000	0	-0.32	2	2
Syndecan-2/Kininogen	0.009	0.057	-10000	0	-0.21	25	25
ITGB1	0.026	0.02	-10000	0	-0.35	1	1
SRC	0.028	0.049	0.18	38	-10000	0	38
Syndecan-2/CASK/Protein 4.1	0.021	0.018	-10000	0	-0.19	2	2
extracellular matrix organization	0.024	0.017	-10000	0	-0.22	1	1
actin cytoskeleton reorganization	0.003	0.069	-10000	0	-0.2	41	41
Syndecan-2/Caveolin-2/Ras	0.034	0.027	-10000	0	-0.19	3	3
Syndecan-2/Laminin alpha3	0.018	0.039	-10000	0	-0.21	11	11
Syndecan-2/RasGAP	0.042	0.029	-10000	0	-0.18	1	1
alpha5/beta1 Integrin	0.033	0.043	-10000	0	-0.28	7	7
PRKCD	0.027	0.005	-10000	0	-10000	0	0
Syndecan-2 dimer	-0.067	0.11	-10000	0	-0.2	168	168
GO:0007205	0.002	0	-10000	0	-10000	0	0
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	0.028	0.022	0.18	3	-10000	0	3
RHOA	0.027	0.006	-10000	0	-10000	0	0
SDCBP	0.025	0.009	-10000	0	-10000	0	0
TNFRSF13B	-0.069	0.17	-10000	0	-0.38	94	94
RASA1	0.025	0.008	-10000	0	-10000	0	0
alpha2/beta1 Integrin	0.025	0.059	-10000	0	-0.24	18	18
Syndecan-2/Synbindin	0.024	0.02	-10000	0	-0.21	2	2
TGFB1	0.027	0.006	-10000	0	-10000	0	0
CASP3	0.032	0.058	0.19	45	-0.2	1	46
FN1	-0.01	0.11	-10000	0	-0.35	41	41
Syndecan-2/IL8	-0.072	0.11	-10000	0	-0.2	176	176
SDC2	0.009	0.019	-10000	0	-0.25	2	2
KNG1	-0.004	0.098	-10000	0	-0.35	30	30
Syndecan-2/Neurofibromin	0.024	0.02	-10000	0	-0.21	2	2
TRAPPC4	0.027	0.006	-10000	0	-10000	0	0
CSF2	-0.066	0.16	-10000	0	-0.35	99	99
Syndecan-2/TGFB1	0.024	0.017	-10000	0	-0.22	1	1
Syndecan-2/Syntenin/PI-4-5-P2	0.022	0.018	-10000	0	-0.19	2	2
Syndecan-2/Ezrin	0.036	0.024	-10000	0	-0.19	2	2
PRKACA	0.035	0.06	0.19	50	-0.19	2	52
angiogenesis	-0.072	0.11	-10000	0	-0.2	176	176
MMP2	0.025	0.028	-10000	0	-0.37	2	2
IL8	-0.16	0.19	-10000	0	-0.35	198	198
calcineurin-NFAT signaling pathway	-0.025	0.097	-10000	0	-0.22	78	78

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.026	0.008	-10000	0	-10000	0	0
EPHB2	-0.16	0.19	-10000	0	-0.35	204	204
EFNB1	-0.003	0.044	-10000	0	-0.25	12	12
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.083	0.14	-10000	0	-0.33	60	60
Ephrin B2/EPHB1-2	-0.09	0.14	-10000	0	-0.22	200	200
neuron projection morphogenesis	-0.086	0.13	-10000	0	-0.31	60	60
Ephrin B1/EPHB1-2/Tiam1	-0.096	0.15	-10000	0	-0.34	65	65
DNM1	0.016	0.064	-10000	0	-0.35	12	12
cell-cell signaling	0	0.004	-10000	0	-10000	0	0
MAP2K4	-0.025	0.11	0.26	1	-0.45	23	24
YES1	-0.027	0.16	-10000	0	-0.65	26	26
Ephrin B1/EPHB1-2/NCK2	-0.089	0.15	-10000	0	-0.34	60	60
PI3K	0.007	0.12	-10000	0	-0.43	26	26
mol:GDP	-0.096	0.15	-10000	0	-0.34	65	65
ITGA2B	0.015	0.067	-10000	0	-0.36	13	13
endothelial cell proliferation	0.032	0.014	-10000	0	-10000	0	0
FYN	-0.028	0.17	-10000	0	-0.65	27	27
MAP3K7	-0.026	0.12	0.22	1	-0.47	25	26
FGR	-0.024	0.16	-10000	0	-0.66	24	24
TIAM1	0.017	0.062	-10000	0	-0.37	10	10
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
RGS3	0.027	0.006	-10000	0	-10000	0	0
cell adhesion	-0.009	0.12	-10000	0	-0.43	23	23
LYN	-0.026	0.16	-10000	0	-0.66	25	25
Ephrin B1/EPHB1-2/Src Family Kinases	-0.03	0.15	-10000	0	-0.58	27	27
Ephrin B1/EPHB1-2	-0.022	0.12	-10000	0	-0.54	19	19
SRC	-0.026	0.16	-10000	0	-0.64	26	26
ITGB3	0.023	0.042	-10000	0	-0.36	5	5
EPHB1	-0.044	0.15	-10000	0	-0.35	77	77
EPHB4	0.026	0.008	-10000	0	-10000	0	0
RAC1	0.026	0.008	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.032	0.014	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	0.028	0.06	-10000	0	-0.25	18	18
BLK	-0.044	0.17	-10000	0	-0.69	24	24
HCK	-0.025	0.16	-10000	0	-0.64	25	25
regulation of stress fiber formation	0.089	0.15	0.34	60	-10000	0	60
MAPK8	-0.025	0.11	0.24	1	-0.43	22	23
Ephrin B1/EPHB1-2/RGS3	-0.089	0.15	-10000	0	-0.34	61	61
endothelial cell migration	0.003	0.11	0.24	16	-0.41	17	33
NCK2	0.028	0.004	-10000	0	-10000	0	0
PTPN13	0.009	0.096	-10000	0	-0.45	17	17
regulation of focal adhesion formation	0.089	0.15	0.34	60	-10000	0	60
chemotaxis	0.089	0.15	0.34	61	-10000	0	61
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
Rac1/GTP	-0.085	0.14	-10000	0	-0.32	60	60
angiogenesis	-0.025	0.12	-10000	0	-0.51	23	23
LCK	-0.027	0.16	-10000	0	-0.65	26	26

×

TCGA08_p53

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
CDKN2A	-0.067	0.11	-10000	0	-0.24	121	121
TP53	-0.025	0.065	0.18	1	-0.25	24	25
Senescence	-0.026	0.067	0.18	1	-0.25	25	26
Apoptosis	-0.026	0.067	0.18	1	-0.25	25	26
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.045	0.094	0.27	33	-0.34	1	34
MDM4	0.027	0.005	-10000	0	-10000	0	0

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.021	0.14	-10000	0	-0.4	18	18
SMAD6-7/SMURF1	0.045	0.023	-10000	0	-10000	0	0
NOG	0.002	0.097	-10000	0	-0.37	26	26
SMAD9	-0.053	0.19	-10000	0	-0.58	44	44
SMAD4	0.024	0.01	-10000	0	-10000	0	0
SMAD5	-0.037	0.12	-10000	0	-0.34	36	36
BMP7/USAG1	-0.12	0.18	-10000	0	-0.33	176	176
SMAD5/SKI	-0.041	0.14	-10000	0	-0.35	41	41
SMAD1	0.014	0.062	-10000	0	-0.43	4	4
BMP2	0.023	0.03	-10000	0	-0.38	2	2
SMAD1/SMAD1/SMAD4	0.024	0.059	-10000	0	-0.36	3	3
BMPR1A	0.025	0.021	-10000	0	-0.38	1	1
BMPR1B	-0.026	0.14	-10000	0	-0.38	53	53
BMPR1A-1B/BAMBI	-0.023	0.13	-10000	0	-0.24	106	106
AHSG	0.008	0.075	-10000	0	-0.35	17	17
CER1	0.01	0.057	-10000	0	-0.35	10	10
BMP2-4/CER1	0.031	0.055	-10000	0	-0.23	14	14
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.06	0.14	-10000	0	-0.36	51	51
BMP2-4 (homodimer)	0.031	0.046	-10000	0	-0.29	7	7
RGMB	0.025	0.022	-10000	0	-0.38	1	1
BMP6/BMPR2/BMPR1A-1B	0.027	0.094	-10000	0	-0.22	44	44
RGMA	-0.098	0.19	-10000	0	-0.38	125	125
SMURF1	0.025	0.009	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.051	0.13	-10000	0	-0.33	49	49
BMP2-4/USAG1	-0.079	0.14	-10000	0	-0.23	181	181
SMAD6/SMURF1/SMAD5	-0.039	0.13	-10000	0	-0.34	45	45
SOSTDC1	-0.16	0.2	-10000	0	-0.38	189	189
BMP7/BMPR2/BMPR1A-1B	-0.011	0.12	-10000	0	-0.24	76	76
SKI	0.026	0.007	-10000	0	-10000	0	0
BMP6 (homodimer)	0.025	0.021	-10000	0	-0.38	1	1
HFE2	0.012	0.061	-10000	0	-0.35	11	11
ZFYVE16	0.026	0.008	-10000	0	-10000	0	0
MAP3K7	0.027	0.006	-10000	0	-10000	0	0
BMP2-4/CHRD	0.039	0.057	-10000	0	-0.28	10	10
SMAD5/SMAD5/SMAD4	-0.041	0.14	-10000	0	-0.34	42	42
MAPK1	0.027	0.006	-10000	0	-10000	0	0
TAK1/TAB family	-0.034	0.12	-10000	0	-0.31	36	36
BMP7 (homodimer)	-0.037	0.14	-10000	0	-0.38	60	60
NUP214	0.027	0.005	-10000	0	-10000	0	0
BMP6/FETUA	0.024	0.055	-10000	0	-0.24	16	16
SMAD1/SKI	0.02	0.078	0.25	1	-0.42	6	7
SMAD6	0.027	0.005	-10000	0	-10000	0	0
CTDSP2	0.027	0.006	-10000	0	-10000	0	0
BMP2-4/FETUA	0.035	0.057	-10000	0	-0.22	16	16
MAP3K7IP1	0	0	-10000	0	-10000	0	0
GREM1	-0.045	0.15	-10000	0	-0.36	77	77
BMPR2 (homodimer)	0.028	0.003	-10000	0	-10000	0	0
GADD34/PP1CA	0.049	0.02	-10000	0	-10000	0	0
BMPR1A-1B (homodimer)	-0.002	0.1	-10000	0	-0.27	52	52
CHRDL1	-0.13	0.2	-10000	0	-0.38	153	153
ENDOFIN/SMAD1	0.02	0.077	0.25	1	-0.42	6	7
SMAD6-7/SMURF1/SMAD1	0.039	0.072	-10000	0	-0.39	4	4
SMAD6/SMURF1	0.025	0.009	-10000	0	-10000	0	0
BAMBI	-0.033	0.14	-10000	0	-0.35	65	65
SMURF2	0.027	0.005	-10000	0	-10000	0	0
BMP2-4/CHRDL1	-0.047	0.14	-10000	0	-0.24	135	135
BMP2-4/GREM1	-0.003	0.11	-10000	0	-0.21	80	80
SMAD7	0.025	0.009	-10000	0	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.048	0.19	-10000	0	-0.52	52	52
SMAD1/SMAD6	0.018	0.074	0.25	1	-0.4	5	6
TAK1/SMAD6	0.036	0.015	-10000	0	-10000	0	0
BMP7	-0.037	0.14	-10000	0	-0.38	60	60
BMP6	0.025	0.021	-10000	0	-0.38	1	1
MAP3K7IP2	0	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.045	0.14	-10000	0	-0.35	47	47
PPM1A	0.027	0.005	-10000	0	-10000	0	0
SMAD1/SMURF2	0.021	0.077	-10000	0	-0.44	5	5
SMAD7/SMURF1	0.033	0.017	-10000	0	-10000	0	0
CTDSPL	0.027	0.005	-10000	0	-10000	0	0
PPP1CA	0.027	0.006	-10000	0	-10000	0	0
XIAP	0.028	0.004	-10000	0	-10000	0	0
CTDSP1	0.028	0.004	-10000	0	-10000	0	0
PPP1R15A	0.027	0.006	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.085	0.18	-10000	0	-0.4	77	77
CHRD	0.018	0.057	-10000	0	-0.38	8	8
BMPR2	0.028	0.003	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.061	0.14	-10000	0	-0.33	61	61
BMP4	0.021	0.051	-10000	0	-0.36	7	7
FST	-0.009	0.11	-10000	0	-0.37	36	36
BMP2-4/NOG	0.027	0.077	-10000	0	-0.22	33	33
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.003	0.12	-10000	0	-0.39	9	9

×

TCGA08_retinoblastoma

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
CDKN2B	0.022	0.031	-10000	0	-0.35	2	2
CDKN2C	0.033	0.028	-10000	0	-0.32	1	1
CDKN2A	-0.086	0.17	-10000	0	-0.35	121	121
CCND2	0.017	0.041	0.14	9	-10000	0	9
RB1	-0.021	0.051	0.3	1	-0.18	11	12
CDK4	0.024	0.053	0.19	14	-10000	0	14
CDK6	0.023	0.052	0.17	21	-10000	0	21
G1/S progression	0.04	0.075	0.2	50	-0.3	1	51

×

Canonical 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.027	0.014	-10000	0	-10000	0	0
AES	0.026	0.013	-10000	0	-10000	0	0
FBXW11	0.027	0.006	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.035	0.016	-10000	0	-10000	0	0
SMAD4	0.024	0.01	-10000	0	-10000	0	0
DKK2	-0.075	0.17	-10000	0	-0.35	111	111
TLE1	0.026	0.024	-10000	0	-0.39	1	1
MACF1	0.027	0.019	-10000	0	-0.35	1	1
CTNNB1	0.016	0.12	0.33	11	-0.46	7	18
WIF1	-0.065	0.16	-10000	0	-0.38	86	86
beta catenin/RanBP3	0	0.11	0.38	11	-0.48	4	15
KREMEN2	-0.049	0.15	-10000	0	-0.35	82	82
DKK1	-0.15	0.19	-10000	0	-0.36	186	186
beta catenin/beta TrCP1	0.027	0.11	0.33	11	-0.48	5	16
FZD1	0.025	0.009	-10000	0	-10000	0	0
AXIN2	-0.012	0.19	0.64	7	-1.3	6	13
AXIN1	0.027	0.007	-10000	0	-10000	0	0
RAN	0.027	0.005	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.007	0.13	-10000	0	-0.56	16	16
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	-0.016	0.19	0.32	2	-0.64	25	27
Axin1/APC/GSK3	0.038	0.071	0.24	8	-0.36	3	11
Axin1/APC/GSK3/beta catenin/Macf1	0.013	0.11	0.25	6	-0.41	12	18
HNF1A	0.018	0.06	-10000	0	-0.35	10	10
CTBP1	0.026	0.013	-10000	0	-10000	0	0
MYC	0.12	0.26	0.59	81	-1.2	2	83
RANBP3	0.027	0.006	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.066	0.14	-10000	0	-0.22	171	171
NKD1	-0.02	0.13	-10000	0	-0.37	48	48
TCF4	0.024	0.014	-10000	0	-10000	0	0
TCF3	0.026	0.013	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0.046	0.062	-10000	0	-0.2	17	17
Ran/GTP	0.02	0.004	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	-0.015	0.12	0.41	6	-0.47	12	18
LEF1	0.016	0.064	-10000	0	-0.35	12	12
DVL1	0.026	0.044	-10000	0	-0.34	1	1
CSNK2A1	0.025	0.009	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.007	0.16	0.35	2	-0.6	19	21
DKK1/LRP6/Kremen 2	-0.11	0.15	-10000	0	-0.23	228	228
LRP6	0.027	0.007	-10000	0	-10000	0	0
CSNK1A1	0.027	0.014	-10000	0	-10000	0	0
NLK	0.028	0.005	-10000	0	-10000	0	0
CCND1	0.037	0.14	0.58	23	-10000	0	23
WNT1	0.006	0.09	-10000	0	-0.38	21	21
GSK3A	0.027	0.006	-10000	0	-10000	0	0
GSK3B	0.028	0.005	-10000	0	-10000	0	0
FRAT1	0.027	0.006	-10000	0	-10000	0	0
PPP2R5D	0.044	0.071	0.24	28	-0.34	2	30
APC	0.012	0.079	0.2	46	-10000	0	46
WNT1/LRP6/FZD1	0.035	0.083	0.2	58	-0.31	3	61
CREBBP	0.026	0.014	-10000	0	-10000	0	0

×

Endothelins

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
AKT1	-0.013	0.14	0.25	7	-0.42	11	18
PTK2B	0.025	0.009	-10000	0	-10000	0	0
mol:Ca2+	0.005	0.14	-10000	0	-0.62	6	6
EDN1	0.007	0.11	0.21	3	-0.33	12	15
EDN3	-0.06	0.16	-10000	0	-0.38	82	82
EDN2	-0.049	0.16	-10000	0	-0.38	77	77
HRAS/GDP	-0.019	0.13	0.26	4	-0.42	15	19
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	0.008	0.095	-10000	0	-0.34	12	12
ADCY4	-0.021	0.12	0.21	10	-0.37	15	25
ADCY5	-0.059	0.16	0.21	8	-0.36	53	61
ADCY6	-0.02	0.12	0.22	5	-0.38	14	19
ADCY7	-0.02	0.12	0.21	9	-0.37	15	24
ADCY1	-0.025	0.12	0.2	11	-0.36	18	29
ADCY2	-0.047	0.14	0.22	4	-0.36	36	40
ADCY3	-0.02	0.12	0.21	10	-0.37	15	25
ADCY8	-0.026	0.12	0.22	4	-0.36	15	19
ADCY9	-0.023	0.12	0.21	7	-0.37	15	22
arachidonic acid secretion	-0.026	0.15	0.24	5	-0.47	27	32
ETB receptor/Endothelin-1/Gq/GTP	0.004	0.07	-10000	0	-0.26	10	10
GNAO1	-0.055	0.16	-10000	0	-0.38	82	82
HRAS	0.026	0.007	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	0.042	0.16	0.3	8	-0.39	10	18
ETA receptor/Endothelin-1/Gs/GTP	0.021	0.16	0.29	7	-0.38	15	22
mol:GTP	0.001	0.002	-10000	0	-10000	0	0
COL3A1	-0.037	0.18	0.25	6	-0.42	58	64
EDNRB	0.01	0.053	-10000	0	-0.38	4	4
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.02	0.15	0.25	7	-0.5	13	20
CYSLTR1	-0.03	0.17	0.25	7	-0.49	31	38
SLC9A1	0	0.081	0.18	4	-0.25	12	16
mol:GDP	-0.029	0.14	0.25	5	-0.42	20	25
SLC9A3	-0.14	0.27	-10000	0	-0.6	65	65
RAF1	-0.036	0.14	0.24	7	-0.44	26	33
JUN	0.002	0.14	-10000	0	-0.68	6	6
JAK2	-0.015	0.13	0.25	7	-0.32	30	37
mol:IP3	0.005	0.091	-10000	0	-0.36	10	10
ETA receptor/Endothelin-1	0.028	0.19	0.36	6	-0.37	30	36
PLCB1	0.023	0.028	-10000	0	-0.35	2	2
PLCB2	0.023	0.038	-10000	0	-0.36	4	4
ETA receptor/Endothelin-3	-0.047	0.14	-10000	0	-0.29	91	91
FOS	-0.054	0.22	0.33	1	-0.82	27	28
Gai/GDP	-0.15	0.32	-10000	0	-0.68	104	104
CRK	0.026	0.008	-10000	0	-10000	0	0
mol:Ca ++	-0.011	0.13	0.23	6	-0.41	13	19
BCAR1	0.027	0.007	-10000	0	-10000	0	0
PRKCB1	0	0.1	0.19	2	-0.37	15	17
GNAQ	0.027	0.009	-10000	0	-10000	0	0
GNAZ	0.001	0.1	-10000	0	-0.38	26	26
GNAL	-0.001	0.1	-10000	0	-0.38	27	27
Gs family/GDP	-0.033	0.14	0.25	4	-0.4	21	25
ETA receptor/Endothelin-1/Gq/GTP	0.007	0.095	0.19	3	-0.34	9	12
MAPK14	0.001	0.074	0.23	2	-0.31	8	10
TRPC6	0.005	0.14	-10000	0	-0.66	6	6
GNAI2	0.027	0.005	-10000	0	-10000	0	0
GNAI3	0.027	0.005	-10000	0	-10000	0	0
GNAI1	0.02	0.054	-10000	0	-0.38	7	7
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	0.006	0.074	-10000	0	-0.31	7	7
ETB receptor/Endothelin-2	-0.029	0.12	-10000	0	-0.28	75	75
ETB receptor/Endothelin-3	-0.039	0.12	-10000	0	-0.28	81	81
ETB receptor/Endothelin-1	0.013	0.11	-10000	0	-0.3	12	12
MAPK3	-0.05	0.2	0.33	1	-0.7	28	29
MAPK1	-0.052	0.2	0.34	1	-0.7	28	29
Rac1/GDP	-0.02	0.13	0.22	2	-0.42	16	18
cAMP biosynthetic process	-0.042	0.15	0.24	11	-0.39	31	42
MAPK8	-0.001	0.16	-10000	0	-0.62	14	14
SRC	0.024	0.01	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.039	0.12	-10000	0	-0.36	34	34
p130Cas/CRK/Src/PYK2	-0.023	0.15	0.3	10	-0.54	11	21
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.019	0.13	0.22	3	-0.41	16	19
COL1A2	-0.027	0.18	0.25	4	-0.42	52	56
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.037	0.14	-10000	0	-0.28	83	83
mol:DAG	0.005	0.091	-10000	0	-0.36	10	10
MAP2K2	-0.041	0.16	0.3	2	-0.52	30	32
MAP2K1	-0.043	0.16	0.3	2	-0.52	30	32
EDNRA	0.004	0.12	0.21	3	-0.35	16	19
positive regulation of muscle contraction	-0.002	0.12	0.22	25	-0.38	10	35
Gq family/GDP	-0.012	0.12	-10000	0	-0.4	15	15
HRAS/GTP	-0.032	0.13	0.25	5	-0.41	24	29
PRKCH	0.003	0.092	0.2	2	-0.35	12	14
RAC1	0.026	0.008	-10000	0	-10000	0	0
PRKCA	0	0.1	0.2	4	-0.37	15	19
PRKCB	-0.01	0.11	0.19	1	-0.39	20	21
PRKCE	-0.001	0.1	0.25	3	-0.38	14	17
PRKCD	0.002	0.091	0.19	1	-0.34	12	13
PRKCG	-0.065	0.13	0.22	5	-0.37	24	29
regulation of vascular smooth muscle contraction	-0.066	0.26	0.34	1	-0.95	27	28
PRKCQ	-0.005	0.11	0.22	3	-0.4	15	18
PLA2G4A	-0.03	0.16	0.24	5	-0.52	27	32
GNA14	0.021	0.053	-10000	0	-0.38	7	7
GNA15	0.023	0.042	-10000	0	-0.35	5	5
GNA12	0.026	0.008	-10000	0	-10000	0	0
GNA11	0.027	0.007	-10000	0	-10000	0	0
Rac1/GTP	0.042	0.16	0.3	8	-0.39	10	18
MMP1	-0.12	0.19	0.4	2	-0.34	157	159

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.058	0.16	0.41	3	-0.43	42	45
IKBKB	-0.025	0.1	0.47	2	-0.33	17	19
AKT1	-0.028	0.11	0.32	9	-0.25	21	30
IKBKG	-0.017	0.091	0.42	2	-0.28	14	16
CALM1	-0.039	0.13	0.28	1	-0.41	32	33
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
MAP3K1	-0.067	0.2	0.44	2	-0.55	43	45
MAP3K7	0.027	0.006	-10000	0	-10000	0	0
mol:Ca2+	-0.037	0.14	-10000	0	-0.42	34	34
DOK1	0.027	0.019	-10000	0	-0.35	1	1
AP-1	-0.034	0.1	0.31	5	-0.26	34	39
LYN	0.025	0.009	-10000	0	-10000	0	0
BLNK	0.011	0.08	-10000	0	-0.38	16	16
SHC1	0.027	0.005	-10000	0	-10000	0	0
BCR complex	-0.031	0.15	-10000	0	-0.33	78	78
CD22	-0.073	0.18	-10000	0	-0.54	38	38
CAMK2G	-0.032	0.13	0.27	2	-0.38	30	32
CSNK2A1	0.025	0.009	-10000	0	-10000	0	0
INPP5D	0.025	0.034	-10000	0	-0.36	3	3
SHC/GRB2/SOS1	-0.015	0.11	-10000	0	-0.36	22	22
GO:0007205	-0.04	0.14	0.3	1	-0.42	37	38
SYK	0.026	0.021	-10000	0	-0.38	1	1
ELK1	-0.039	0.14	0.28	1	-0.41	34	35
NFATC1	-0.061	0.16	0.28	3	-0.42	50	53
B-cell antigen/BCR complex	-0.031	0.15	-10000	0	-0.33	78	78
PAG1/CSK	0.034	0.021	-10000	0	-0.25	1	1
NFKBIB	0.007	0.047	0.18	4	-0.12	15	19
HRAS	-0.034	0.13	0.3	2	-0.4	30	32
NFKBIA	0.007	0.047	0.18	4	-0.12	15	19
NF-kappa-B/RelA/I kappa B beta	0.012	0.042	0.18	4	-10000	0	4
RasGAP/Csk	0.006	0.14	-10000	0	-0.28	61	61
mol:GDP	-0.037	0.14	0.28	1	-0.41	35	36
PTEN	0.026	0.008	-10000	0	-10000	0	0
CD79B	-0.002	0.1	-10000	0	-0.38	30	30
NF-kappa-B/RelA/I kappa B alpha	0.012	0.041	0.18	4	-10000	0	4
GRB2	0.027	0.005	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.081	0.2	0.45	2	-0.52	50	52
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
mol:IP3	-0.039	0.14	-10000	0	-0.44	34	34
CSK	0.027	0.005	-10000	0	-10000	0	0
FOS	-0.045	0.14	0.28	3	-0.42	33	36
CHUK	-0.024	0.1	0.42	2	-0.3	26	28
IBTK	0.027	0.006	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.043	0.15	0.27	4	-0.4	32	36
PTPN6	-0.071	0.17	-10000	0	-0.57	31	31
RELA	0.027	0.005	-10000	0	-10000	0	0
BCL2A1	0.007	0.033	0.22	2	-10000	0	2
VAV2	-0.075	0.19	-10000	0	-0.54	47	47
ubiquitin-dependent protein catabolic process	0.01	0.046	0.18	4	-0.12	15	19
BTK	-0.006	0.16	-10000	0	-0.98	11	11
CD19	-0.075	0.19	-10000	0	-0.52	50	50
MAP4K1	0.013	0.073	-10000	0	-0.37	14	14
CD72	-0.029	0.13	-10000	0	-0.35	59	59
PAG1	0.023	0.021	-10000	0	-0.35	1	1
MAPK14	-0.054	0.18	0.43	3	-0.47	41	44
SH3BP5	0.028	0.004	-10000	0	-10000	0	0
PIK3AP1	-0.038	0.15	-10000	0	-0.45	34	34
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.068	0.19	-10000	0	-0.52	46	46
RAF1	-0.032	0.12	0.3	2	-0.4	26	28
RasGAP/p62DOK/SHIP	0.007	0.14	-10000	0	-0.39	28	28
CD79A	-0.048	0.16	-10000	0	-0.38	75	75
re-entry into mitotic cell cycle	-0.034	0.1	0.31	5	-0.26	33	38
RASA1	0.025	0.008	-10000	0	-10000	0	0
MAPK3	-0.026	0.11	0.35	3	-0.37	18	21
MAPK1	-0.026	0.11	0.3	3	-0.36	19	22
CD72/SHP1	-0.073	0.18	0.27	3	-0.48	47	50
NFKB1	0.027	0.005	-10000	0	-10000	0	0
MAPK8	-0.056	0.17	0.44	3	-0.46	41	44
actin cytoskeleton organization	-0.059	0.17	0.27	2	-0.46	43	45
NF-kappa-B/RelA	0.026	0.078	0.28	5	-0.2	6	11
Calcineurin	-0.009	0.12	0.26	1	-0.39	20	21
PI3K	-0.064	0.15	-10000	0	-0.42	48	48
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.034	0.15	-10000	0	-0.46	35	35
SOS1	0.028	0.003	-10000	0	-10000	0	0
Bam32/HPK1	-0.083	0.27	-10000	0	-0.79	45	45
DAPP1	-0.11	0.3	-10000	0	-0.9	46	46
cytokine secretion	-0.056	0.15	0.28	3	-0.39	50	53
mol:DAG	-0.039	0.14	-10000	0	-0.44	34	34
PLCG2	0.019	0.055	-10000	0	-0.37	8	8
MAP2K1	-0.03	0.12	0.28	2	-0.37	25	27
B-cell antigen/BCR complex/FcgammaRIIB	-0.017	0.15	-10000	0	-0.3	80	80
mol:PI-3-4-5-P3	-0.057	0.1	0.21	1	-0.32	37	38
ETS1	-0.03	0.12	0.28	3	-0.36	28	31
B-cell antigen/BCR complex/LYN/SYK/BLNK	0.008	0.13	-10000	0	-0.39	22	22
B-cell antigen/BCR complex/LYN	-0.052	0.17	-10000	0	-0.54	33	33
MALT1	0.025	0.009	-10000	0	-10000	0	0
TRAF6	0.027	0.005	-10000	0	-10000	0	0
RAC1	-0.062	0.18	0.29	1	-0.5	41	42
B-cell antigen/BCR complex/LYN/SYK	-0.043	0.18	-10000	0	-0.55	31	31
CARD11	-0.067	0.16	0.29	5	-0.41	48	53
FCGR2B	0.012	0.077	-10000	0	-0.38	15	15
PPP3CA	0.026	0.027	-10000	0	-0.35	2	2
BCL10	0.028	0.004	-10000	0	-10000	0	0
IKK complex	0	0.053	0.18	9	-0.12	9	18
PTPRC	0.01	0.08	-10000	0	-0.36	19	19
PDPK1	-0.035	0.082	0.2	8	-0.23	28	36
PPP3CB	0.027	0.006	-10000	0	-10000	0	0
PPP3CC	0.025	0.009	-10000	0	-10000	0	0
POU2F2	0.01	0.033	0.42	1	-10000	0	1

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.006	0.003	-10000	0	-10000	0	0
GNB1/GNG2	0.018	0.084	-10000	0	-0.2	50	50
regulation of S phase of mitotic cell cycle	-0.004	0.071	-10000	0	-0.21	39	39
GNAO1	-0.055	0.16	-10000	0	-0.38	82	82
HRAS	0.026	0.007	-10000	0	-10000	0	0
SHBG/T-DHT	0.007	0.044	-10000	0	-0.2	17	17
PELP1	0.026	0.007	-10000	0	-10000	0	0
AKT1	0.007	0.002	-10000	0	-10000	0	0
MAP2K1	-0.006	0.089	0.18	48	-0.28	3	51
T-DHT/AR	-0.016	0.095	-10000	0	-0.27	51	51
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.002	-10000	0	-0.008	23	23
GNAI2	0.027	0.005	-10000	0	-10000	0	0
GNAI3	0.027	0.005	-10000	0	-10000	0	0
GNAI1	0.02	0.054	-10000	0	-0.38	7	7
mol:GDP	-0.037	0.11	-10000	0	-0.32	51	51
cell proliferation	-0.015	0.13	0.29	7	-0.4	20	27
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
FOS	-0.026	0.19	0.26	2	-0.72	24	26
mol:Ca2+	-0.014	0.031	-10000	0	-0.08	57	57
MAPK3	-0.009	0.11	0.27	10	-0.3	17	27
MAPK1	-0.008	0.1	0.21	4	-0.43	13	17
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
mol:IP3	0	0.001	-10000	0	-0.005	23	23
cAMP biosynthetic process	0	0.048	0.25	1	-0.19	17	18
GNG2	0.027	0.019	-10000	0	-0.35	1	1
potassium channel inhibitor activity	0	0.001	-10000	0	-0.005	23	23
HRAS/GTP	0.016	0.073	-10000	0	-0.19	33	33
actin cytoskeleton reorganization	0.034	0.019	-10000	0	-10000	0	0
SRC	0.024	0.01	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.005	23	23
PI3K	0.033	0.013	-10000	0	-10000	0	0
apoptosis	0.006	0.12	0.37	26	-0.26	5	31
T-DHT/AR/PELP1	0.003	0.085	-10000	0	-0.22	51	51
HRAS/GDP	-0.023	0.11	-10000	0	-0.31	46	46
CREB1	-0.008	0.12	0.27	5	-0.4	26	31
RAC1-CDC42/GTP	0.043	0.023	-10000	0	-10000	0	0
AR	-0.024	0.14	-10000	0	-0.38	51	51
GNB1	0.026	0.007	-10000	0	-10000	0	0
RAF1	0.012	0.091	0.19	50	-0.26	3	53
RAC1-CDC42/GDP	0.003	0.11	-10000	0	-0.32	36	36
T-DHT/AR/PELP1/Src	0.017	0.077	-10000	0	-0.2	42	42
MAP2K2	-0.007	0.086	0.18	44	-0.28	3	47
T-DHT/AR/PELP1/Src/PI3K	-0.004	0.071	-10000	0	-0.21	39	39
GNAZ	0.001	0.1	-10000	0	-0.38	26	26
SHBG	0.008	0.075	-10000	0	-0.35	17	17
Gi family/GNB1/GNG2/GDP	-0.074	0.19	-10000	0	-0.4	80	80
mol:T-DHT	0	0.001	-10000	0	-0.003	17	17
RAC1	0.026	0.008	-10000	0	-10000	0	0
GNRH1	0.005	0.019	-10000	0	-0.27	2	2
Gi family/GTP	-0.051	0.12	-10000	0	-0.32	57	57
CDC42	0.026	0.007	-10000	0	-10000	0	0

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0	0.1	0.26	53	-10000	0	53
KIRREL	0.017	0.046	-10000	0	-0.37	4	4
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.001	0.1	-10000	0	-0.26	53	53
PLCG1	0.023	0.011	-10000	0	-10000	0	0
ARRB2	0.026	0.007	-10000	0	-10000	0	0
WASL	0.027	0.006	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	0.029	0.086	-10000	0	-0.22	17	17
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.004	0.061	-10000	0	-0.22	19	19
FYN	-0.004	0.08	0.24	12	-0.2	21	33
mol:Ca2+	0.024	0.081	-10000	0	-0.19	44	44
mol:DAG	0.025	0.081	-10000	0	-0.19	44	44
NPHS2	0.013	0.041	-10000	0	-0.36	3	3
mol:IP3	0.025	0.081	-10000	0	-0.19	44	44
regulation of endocytosis	0.022	0.075	-10000	0	-0.19	17	17
Nephrin/NEPH1/podocin/Cholesterol	0.015	0.082	-10000	0	-0.19	55	55
establishment of cell polarity	0	0.1	-10000	0	-0.26	53	53
Nephrin/NEPH1/podocin/NCK1-2	0.04	0.087	-10000	0	-0.31	1	1
Nephrin/NEPH1/beta Arrestin2	0.024	0.077	-10000	0	-0.2	17	17
NPHS1	-0.022	0.13	-10000	0	-0.36	51	51
Nephrin/NEPH1/podocin	0.018	0.077	-10000	0	-0.18	41	41
TJP1	0.027	0.005	-10000	0	-10000	0	0
NCK1	0.027	0.005	-10000	0	-10000	0	0
NCK2	0.028	0.004	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.026	0.082	-10000	0	-0.19	44	44
CD2AP	0.026	0.007	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	0.028	0.09	-10000	0	-0.2	41	41
GRB2	0.027	0.005	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.013	0.078	0.21	18	-0.19	18	36
cytoskeleton organization	-0.008	0.073	0.21	6	-0.26	19	25
Nephrin/NEPH1	0.006	0.07	-10000	0	-0.17	53	53
Nephrin/NEPH1/ZO-1	0.019	0.087	-10000	0	-0.2	52	52

×

amb2 Integrin signaling

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
alphaM/beta2 Integrin/proMMP-2	0.025	0.065	-10000	0	-0.22	14	14
alphaM/beta2 Integrin/GPIbA	0.016	0.08	-10000	0	-0.23	28	28
alphaM/beta2 Integrin/proMMP-9	-0.032	0.12	-10000	0	-0.23	90	90
PLAUR	0.023	0.038	-10000	0	-0.35	4	4
HMGB1	0.016	0.029	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Talin	0.027	0.06	-10000	0	-0.22	11	11
AGER	0.014	0.035	-10000	0	-0.35	1	1
RAP1A	0.027	0.005	-10000	0	-10000	0	0
SELPLG	0.028	0.004	-10000	0	-10000	0	0
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	0.021	0.1	-10000	0	-0.29	11	11
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	-0.062	0.16	-10000	0	-0.35	92	92
CYR61	0.023	0.043	-10000	0	-0.37	5	5
TLN1	0.026	0.008	-10000	0	-10000	0	0
Rap1/GTP	-0.023	0.092	-10000	0	-0.29	14	14
RHOA	0.027	0.006	-10000	0	-10000	0	0
P-selectin oligomer	-0.024	0.14	-10000	0	-0.38	51	51
MYH2	-0.044	0.097	-10000	0	-0.3	20	20
MST1R	0.023	0.04	-10000	0	-0.38	4	4
leukocyte activation during inflammatory response	-0.075	0.13	-10000	0	-0.27	52	52
APOB	-0.14	0.2	-10000	0	-0.38	176	176
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	0.025	0.028	-10000	0	-0.37	2	2
JAM3	0.027	0.006	-10000	0	-10000	0	0
GP1BA	0.01	0.078	-10000	0	-0.38	16	16
alphaM/beta2 Integrin/CTGF	0.026	0.066	-10000	0	-0.22	15	15
alphaM/beta2 Integrin	-0.036	0.092	-10000	0	-0.28	26	26
JAM3 homodimer	0.027	0.006	-10000	0	-10000	0	0
ICAM2	0.026	0.028	-10000	0	-0.37	2	2
ICAM1	0.018	0.059	-10000	0	-0.35	10	10
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.036	0.093	-10000	0	-0.28	26	26
cell adhesion	0.016	0.079	-10000	0	-0.23	28	28
NFKB1	-0.015	0.14	0.38	2	-0.37	37	39
THY1	-0.003	0.1	-10000	0	-0.35	32	32
RhoA/GDP	0.02	0.004	-10000	0	-10000	0	0
Lipoprotein(a)	-0.09	0.14	-10000	0	-0.23	192	192
alphaM/beta2 Integrin/LRP/tPA	0.038	0.063	-10000	0	-0.22	5	5
IL6	-0.05	0.2	0.37	1	-0.59	37	38
ITGB2	0.009	0.057	-10000	0	-0.36	7	7
elevation of cytosolic calcium ion concentration	0.015	0.094	-10000	0	-0.25	18	18
alphaM/beta2 Integrin/JAM2/JAM3	0.022	0.094	-10000	0	-0.23	35	35
JAM2	-0.009	0.12	-10000	0	-0.38	35	35
alphaM/beta2 Integrin/ICAM1	0.025	0.098	-10000	0	-0.31	5	5
alphaM/beta2 Integrin/uPA/Plg	0.01	0.093	-10000	0	-0.24	16	16
RhoA/GTP	-0.047	0.1	-10000	0	-0.29	30	30
positive regulation of phagocytosis	-0.019	0.082	-10000	0	-0.29	7	7
Ron/MSP	0.014	0.085	-10000	0	-0.25	37	37
alphaM/beta2 Integrin/uPAR/uPA	0.017	0.095	-10000	0	-0.25	17	17
alphaM/beta2 Integrin/uPAR	0.024	0.067	-10000	0	-0.22	17	17
PLAU	-0.007	0.11	-10000	0	-0.35	36	36
PLAT	0.025	0.009	-10000	0	-10000	0	0
actin filament polymerization	-0.043	0.094	-10000	0	-0.29	21	21
MST1	-0.004	0.1	-10000	0	-0.35	34	34
alphaM/beta2 Integrin/lipoprotein(a)	-0.074	0.13	-10000	0	-0.27	52	52
TNF	-0.032	0.15	-10000	0	-0.56	15	15
RAP1B	0.027	0.007	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPA	0.004	0.093	-10000	0	-0.22	47	47
fibrinolysis	0.009	0.092	-10000	0	-0.24	16	16
HCK	0.024	0.01	-10000	0	-10000	0	0
dendritic cell antigen processing and presentation	-0.036	0.093	-10000	0	-0.28	26	26
VTN	-0.051	0.16	-10000	0	-0.37	81	81
alphaM/beta2 Integrin/CYR61	0.025	0.07	-10000	0	-0.23	18	18
LPA	-0.005	0.098	-10000	0	-0.35	30	30
LRP1	0.027	0.005	-10000	0	-10000	0	0
cell migration	-0.032	0.1	-10000	0	-0.3	20	20
FN1	-0.01	0.11	-10000	0	-0.35	41	41
alphaM/beta2 Integrin/Thy1	0.009	0.091	-10000	0	-0.23	42	42
MPO	0.022	0.046	-10000	0	-0.35	6	6
KNG1	-0.004	0.098	-10000	0	-0.35	30	30
RAP1/GDP	0.035	0.01	-10000	0	-10000	0	0
ROCK1	-0.041	0.098	0.2	3	-0.3	20	23
ELA2	0	0	-10000	0	-10000	0	0
PLG	0.015	0.041	-10000	0	-0.35	5	5
CTGF	0.025	0.028	-10000	0	-0.37	2	2
alphaM/beta2 Integrin/Hck	0.024	0.062	-10000	0	-0.22	13	13
ITGAM	0.011	0.054	-10000	0	-0.37	6	6
alphaM/beta2 Integrin/P-Selectin/PSGL1	0.013	0.1	-10000	0	-0.22	50	50
HP	-0.03	0.13	-10000	0	-0.35	60	60
leukocyte adhesion	-0.013	0.11	-10000	0	-0.33	14	14
SELP	-0.024	0.14	-10000	0	-0.38	51	51

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.066	0.07	-10000	0	-10000	0	0
SMARCC2	0.028	0.01	-10000	0	-10000	0	0
SMARCC1	0.028	0.01	-10000	0	-10000	0	0
TBX21	-0.083	0.12	0.34	1	-0.46	18	19
SUMO2	0.027	0.008	-10000	0	-10000	0	0
STAT1 (dimer)	0.023	0.059	-10000	0	-0.35	10	10
FKBP4	0.026	0.007	-10000	0	-10000	0	0
FKBP5	0.025	0.029	-10000	0	-0.38	2	2
GR alpha/HSP90/FKBP51/HSP90	0.1	0.093	0.28	29	-0.27	1	30
PRL	-0.059	0.11	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/TIF2	0.18	0.2	0.52	62	-10000	0	62
RELA	-0.045	0.075	-10000	0	-0.22	10	10
FGG	0.089	0.22	0.42	50	-0.38	37	87
GR beta/TIF2	0.091	0.099	0.28	36	-0.32	1	37
IFNG	-0.24	0.21	-10000	0	-0.6	72	72
apoptosis	-0.007	0.16	0.48	11	-0.51	11	22
CREB1	0.002	0.089	-10000	0	-0.31	24	24
histone acetylation	-0.032	0.12	0.35	10	-0.34	16	26
BGLAP	-0.063	0.11	-10000	0	-1	1	1
GR/PKAc	0.1	0.094	0.29	17	-0.22	3	20
NF kappa B1 p50/RelA	-0.072	0.13	-10000	0	-0.32	28	28
SMARCD1	0.028	0.009	-10000	0	-10000	0	0
MDM2	0.064	0.074	0.2	55	-0.2	2	57
GATA3	0.019	0.061	-10000	0	-0.35	10	10
AKT1	0.023	0.005	-10000	0	-10000	0	0
CSF2	-0.095	0.14	-10000	0	-0.51	10	10
GSK3B	0.027	0.009	-10000	0	-10000	0	0
NR1I3	0	0.16	0.46	12	-0.57	6	18
CSN2	0.1	0.14	0.36	39	-0.28	2	41
BRG1/BAF155/BAF170/BAF60A	0.068	0.033	-10000	0	-0.25	2	2
NFATC1	0.021	0.037	-10000	0	-0.38	2	2
POU2F1	0.024	0.031	-10000	0	-0.35	1	1
CDKN1A	0.007	0.081	-10000	0	-1.2	1	1
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0	0.007	-10000	0	-10000	0	0
SFN	0.015	0.067	-10000	0	-0.37	12	12
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.098	0.1	0.29	21	-0.21	5	26
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.014	0.18	0.44	11	-0.71	14	25
JUN	-0.18	0.13	-10000	0	-0.43	43	43
IL4	-0.072	0.11	-10000	0	-0.47	9	9
CDK5R1	0.024	0.038	-10000	0	-0.35	4	4
PRKACA	0.027	0.005	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.16	0.16	0.19	6	-0.36	113	119
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.11	0.092	0.3	19	-0.24	1	20
cortisol/GR alpha (monomer)	0.21	0.23	0.6	68	-0.36	1	69
NCOA2	0.024	0.022	-10000	0	-0.38	1	1
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.082	0.095	-10000	0	-0.42	22	22
AP-1/NFAT1-c-4	-0.28	0.19	-10000	0	-0.56	87	87
AFP	-0.15	0.12	-10000	0	-0.55	5	5
SUV420H1	0.027	0.005	-10000	0	-10000	0	0
IRF1	0.11	0.12	0.39	19	-10000	0	19
TP53	0.037	0.029	-10000	0	-0.5	1	1
PPP5C	0.027	0.006	-10000	0	-10000	0	0
KRT17	-0.32	0.23	-10000	0	-0.64	83	83
KRT14	-0.16	0.3	-10000	0	-0.97	38	38
TBP	0.031	0.018	-10000	0	-0.29	1	1
CREBBP	0.059	0.078	0.31	26	-0.26	2	28
HDAC1	0.026	0.009	-10000	0	-10000	0	0
HDAC2	0.033	0.014	-10000	0	-10000	0	0
AP-1	-0.28	0.2	-10000	0	-0.56	87	87
MAPK14	0.027	0.01	-10000	0	-10000	0	0
MAPK10	-0.023	0.13	-10000	0	-0.38	50	50
MAPK11	0.026	0.01	-10000	0	-10000	0	0
KRT5	-0.25	0.22	-10000	0	-0.61	77	77
interleukin-1 receptor activity	0.006	0.013	-10000	0	-10000	0	0
NCOA1	0.03	0.003	-10000	0	-10000	0	0
STAT1	0.023	0.059	-10000	0	-0.35	10	10
CGA	-0.13	0.25	-10000	0	-0.9	31	31
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.1	0.14	0.37	49	-0.3	1	50
MAPK3	0.027	0.01	-10000	0	-10000	0	0
MAPK1	0.027	0.01	-10000	0	-10000	0	0
ICAM1	-0.13	0.16	-10000	0	-0.52	25	25
NFKB1	-0.046	0.077	-10000	0	-0.23	13	13
MAPK8	-0.14	0.12	-10000	0	-0.37	46	46
MAPK9	0.027	0.009	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.008	0.16	0.49	11	-0.54	11	22
BAX	0.01	0.063	-10000	0	-10000	0	0
POMC	-0.15	0.32	-10000	0	-1.3	25	25
EP300	0.061	0.078	0.31	27	-0.26	2	29
cortisol/GR alpha (dimer)/p53	0.19	0.2	0.53	61	-10000	0	61
proteasomal ubiquitin-dependent protein catabolic process	0.041	0.065	0.22	18	-0.18	2	20
SGK1	0.063	0.14	-10000	0	-1.2	2	2
IL13	-0.16	0.15	-10000	0	-0.55	22	22
IL6	-0.18	0.27	-10000	0	-0.72	63	63
PRKACG	0.018	0.042	-10000	0	-0.35	5	5
IL5	-0.14	0.13	-10000	0	-0.58	7	7
IL2	-0.21	0.18	-10000	0	-0.59	34	34
CDK5	0.027	0.007	-10000	0	-10000	0	0
PRKACB	0.026	0.029	-10000	0	-0.38	2	2
HSP90AA1	0.025	0.027	-10000	0	-0.35	2	2
IL8	-0.22	0.21	-10000	0	-0.5	97	97
CDK5R1/CDK5	0.037	0.031	-10000	0	-0.25	4	4
NF kappa B1 p50/RelA/PKAc	-0.039	0.11	-10000	0	-0.28	10	10
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.18	0.19	0.5	60	-10000	0	60
SMARCA4	0.027	0.01	-10000	0	-10000	0	0
chromatin remodeling	0.11	0.12	0.34	39	-0.32	1	40
NF kappa B1 p50/RelA/Cbp	0.001	0.13	0.37	9	-0.38	4	13
JUN (dimer)	-0.18	0.13	-10000	0	-0.43	44	44
YWHAH	0.027	0.005	-10000	0	-10000	0	0
VIPR1	-0.098	0.16	-10000	0	-0.57	30	30
NR3C1	0.12	0.14	0.38	59	-0.37	2	61
NR4A1	-0.01	0.14	-10000	0	-0.46	34	34
TIF2/SUV420H1	0.035	0.021	-10000	0	-0.27	1	1
MAPKKK cascade	-0.007	0.16	0.48	11	-0.51	11	22
cortisol/GR alpha (dimer)/Src-1	0.2	0.2	0.52	67	-10000	0	67
PBX1	0.017	0.061	-10000	0	-0.38	8	8
POU1F1	0.019	0.031	-10000	0	-0.35	1	1
SELE	-0.16	0.2	-10000	0	-0.5	68	68
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.11	0.12	0.34	39	-0.32	1	40
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.18	0.19	0.5	60	-10000	0	60
mol:cortisol	0.11	0.13	0.34	67	-10000	0	67
MMP1	-0.2	0.22	-10000	0	-0.48	96	96

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	0.014	0.13	0.28	13	-0.4	20	33
FYN	-0.008	0.14	0.26	15	-0.42	27	42
LAT/GRAP2/SLP76	0.006	0.13	0.25	7	-0.42	23	30
IKBKB	0.025	0.009	-10000	0	-10000	0	0
AKT1	-0.01	0.11	0.24	10	-0.35	26	36
B2M	0.027	0.008	-10000	0	-10000	0	0
IKBKG	-0.011	0.045	0.1	14	-0.14	11	25
MAP3K8	0.026	0.02	-10000	0	-0.35	1	1
mol:Ca2+	-0.021	0.021	0.086	1	-0.082	8	9
integrin-mediated signaling pathway	0.035	0.016	-10000	0	-0.23	1	1
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.018	0.15	0.26	9	-0.48	27	36
TRPV6	-0.12	0.23	1.1	5	-0.54	4	9
CD28	0.011	0.079	-10000	0	-0.36	18	18
SHC1	-0.012	0.15	0.28	13	-0.47	24	37
receptor internalization	-0.013	0.15	0.19	1	-0.51	27	28
PRF1	-0.009	0.18	-10000	0	-0.78	16	16
KRAS	0.025	0.009	-10000	0	-10000	0	0
GRB2	0.027	0.005	-10000	0	-10000	0	0
COT/AKT1	0.003	0.096	0.23	10	-0.29	22	32
LAT	-0.014	0.14	0.25	8	-0.44	27	35
EntrezGene:6955	0	0.002	-10000	0	-10000	0	0
CD3D	0.022	0.047	-10000	0	-0.39	5	5
CD3E	0.023	0.04	-10000	0	-0.38	4	4
CD3G	0.019	0.058	-10000	0	-0.39	8	8
RASGRP2	-0.005	0.05	0.072	3	-0.15	38	41
RASGRP1	0.002	0.12	0.26	12	-0.36	24	36
HLA-A	0	0.003	-10000	0	-10000	0	0
RASSF5	0.026	0.021	-10000	0	-0.38	1	1
RAP1A/GTP/RAPL	0.035	0.016	-10000	0	-0.23	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.02	0.054	0.14	27	-0.13	9	36
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.032	0.061	-10000	0	-0.21	19	19
PRKCA	0.012	0.074	0.16	24	-0.23	12	36
GRAP2	0.016	0.067	-10000	0	-0.38	11	11
mol:IP3	0.033	0.12	0.19	98	-0.35	15	113
EntrezGene:6957	0	0.003	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.004	0.12	-10000	0	-0.56	15	15
ORAI1	0.059	0.16	0.48	5	-0.97	5	10
CSK	-0.013	0.14	0.22	11	-0.44	28	39
B7 family/CD28	-0.017	0.16	0.25	5	-0.39	32	37
CHUK	0.027	0.006	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.021	0.16	0.19	6	-0.48	30	36
PTPN6	-0.016	0.14	0.26	8	-0.45	25	33
VAV1	-0.019	0.14	0.22	7	-0.45	28	35
Monovalent TCR/CD3	0.009	0.077	-10000	0	-0.36	12	12
CBL	0.027	0.006	-10000	0	-10000	0	0
LCK	-0.012	0.14	0.26	13	-0.42	29	42
PAG1	-0.005	0.15	0.21	37	-0.43	28	65
RAP1A	0.027	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.02	0.15	0.2	7	-0.49	27	34
CD80	-0.071	0.17	-10000	0	-0.35	107	107
CD86	0.02	0.053	-10000	0	-0.36	8	8
PDK1/CARD11/BCL10/MALT1	-0.029	0.078	-10000	0	-0.25	21	21
HRAS	0.026	0.007	-10000	0	-10000	0	0
GO:0035030	-0.037	0.12	0.2	7	-0.34	35	42
CD8A	0.016	0.07	-10000	0	-0.39	12	12
CD8B	-0.001	0.11	-10000	0	-0.38	30	30
PTPRC	0.01	0.08	-10000	0	-0.36	19	19
PDK1/PKC theta	-0.009	0.13	0.3	11	-0.43	22	33
CSK/PAG1	-0.005	0.15	0.21	39	-0.44	24	63
SOS1	0.028	0.003	-10000	0	-10000	0	0
peptide-MHC class I	0.02	0.009	-10000	0	-10000	0	0
GRAP2/SLP76	0.005	0.15	0.25	5	-0.46	27	32
STIM1	0.036	0.12	1.3	3	-10000	0	3
RAS family/GTP	0.022	0.069	0.18	21	-0.18	13	34
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.015	0.16	0.19	1	-0.54	27	28
mol:DAG	-0.006	0.084	-10000	0	-0.29	20	20
RAP1A/GDP	0.013	0.026	0.078	17	-0.064	3	20
PLCG1	0.023	0.011	-10000	0	-10000	0	0
CD247	0.021	0.05	-10000	0	-0.39	6	6
cytotoxic T cell degranulation	-0.007	0.18	-10000	0	-0.75	16	16
RAP1A/GTP	-0.002	0.019	-10000	0	-0.06	36	36
mol:PI-3-4-5-P3	-0.013	0.13	0.25	10	-0.4	27	37
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.035	0.14	0.21	61	-0.43	17	78
NRAS	0.027	0.005	-10000	0	-10000	0	0
ZAP70	0.008	0.085	-10000	0	-0.36	21	21
GRB2/SOS1	0.04	0.008	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.005	0.13	0.25	3	-0.41	22	25
MALT1	0.025	0.009	-10000	0	-10000	0	0
TRAF6	0.027	0.005	-10000	0	-10000	0	0
CD8 heterodimer	0.013	0.1	-10000	0	-0.32	34	34
CARD11	-0.069	0.16	-10000	0	-0.35	103	103
PRKCB	0.004	0.083	0.16	21	-0.28	15	36
PRKCE	0.011	0.076	0.16	25	-0.24	13	38
PRKCQ	-0.012	0.15	0.3	9	-0.48	24	33
LCP2	0.027	0.006	-10000	0	-10000	0	0
BCL10	0.028	0.004	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.007	0.1	0.21	13	-0.3	25	38
IKK complex	0.017	0.056	0.13	44	-0.11	10	54
RAS family/GDP	0	0.009	-10000	0	-10000	0	0
MAP3K14	-0.001	0.073	0.16	11	-0.23	19	30
PDPK1	-0.009	0.11	0.25	10	-0.34	22	32
TCR/CD3/MHC I/CD8/Fyn	-0.02	0.18	-10000	0	-0.54	34	34

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.027	0.006	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.027	0.086	-10000	0	-0.25	29	29
NT3 (dimer)/TRKC	-0.051	0.15	-10000	0	-0.3	107	107
NT3 (dimer)/TRKB	-0.09	0.19	-10000	0	-0.3	165	165
SHC/Grb2/SOS1/GAB1/PI3K	0.026	0.013	-10000	0	-10000	0	0
RAPGEF1	0.027	0.005	-10000	0	-10000	0	0
BDNF	0.017	0.062	-10000	0	-0.36	11	11
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
DYNLT1	0.027	0.006	-10000	0	-10000	0	0
NTRK1	0.009	0.084	-10000	0	-0.38	18	18
NTRK2	-0.042	0.15	-10000	0	-0.38	70	70
NTRK3	-0.065	0.17	-10000	0	-0.38	91	91
NT-4/5 (dimer)/TRKB	-0.087	0.17	-10000	0	-0.28	174	174
neuron apoptosis	0.09	0.18	0.41	68	-10000	0	68
SHC 2-3/Grb2	-0.098	0.2	-10000	0	-0.45	68	68
SHC1	0.027	0.005	-10000	0	-10000	0	0
SHC2	-0.1	0.2	-10000	0	-0.45	80	80
SHC3	-0.11	0.19	-10000	0	-0.46	74	74
STAT3 (dimer)	0.03	0.032	-10000	0	-0.28	4	4
NT3 (dimer)/TRKA	-0.059	0.16	-10000	0	-0.26	143	143
RIN/GDP	-0.006	0.092	0.22	8	-0.26	10	18
GIPC1	0.027	0.005	-10000	0	-10000	0	0
KRAS	0.025	0.009	-10000	0	-10000	0	0
DNAJA3	-0.081	0.14	-10000	0	-0.3	105	105
RIN/GTP	0.012	0.019	-10000	0	-0.24	2	2
CCND1	0.016	0.018	-10000	0	-0.32	1	1
MAGED1	0.025	0.035	-10000	0	-0.38	3	3
PTPN11	0.028	0.004	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	0	0.092	-10000	0	-0.35	26	26
SHC/GRB2/SOS1	0.053	0.015	-10000	0	-10000	0	0
GRB2	0.027	0.005	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	0.016	0.097	-10000	0	-0.24	47	47
TRKA/NEDD4-2	0.021	0.066	-10000	0	-0.27	19	19
ELMO1	0.026	0.02	-10000	0	-0.35	1	1
RhoG/GTP/ELMO1/DOCK1	0.034	0.017	-10000	0	-0.2	1	1
NGF	0.003	0.096	-10000	0	-0.38	24	24
HRAS	0.026	0.007	-10000	0	-10000	0	0
DOCK1	0.027	0.006	-10000	0	-10000	0	0
GAB2	0.027	0.006	-10000	0	-10000	0	0
RIT2	0.016	0.027	-10000	0	-0.35	2	2
RIT1	0.027	0.006	-10000	0	-10000	0	0
FRS2	0.026	0.007	-10000	0	-10000	0	0
DNM1	0.016	0.064	-10000	0	-0.35	12	12
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.026	0.008	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.066	0.15	-10000	0	-0.3	104	104
mol:GDP	-0.016	0.13	0.27	11	-0.4	12	23
NGF (dimer)	0.003	0.096	-10000	0	-0.38	24	24
RhoG/GDP	0.019	0.014	-10000	0	-0.24	1	1
RIT1/GDP	-0.004	0.092	0.21	7	-0.27	9	16
TIAM1	0.017	0.062	-10000	0	-0.37	10	10
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.002	0.11	-10000	0	-0.23	78	78
KIDINS220/CRKL/C3G	0.039	0.011	-10000	0	-10000	0	0
SHC/RasGAP	0.037	0.014	-10000	0	-10000	0	0
FRS2 family/SHP2	0.05	0.019	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0.065	0.023	-10000	0	-10000	0	0
RIT1/GTP	0.02	0.004	-10000	0	-10000	0	0
NT3 (dimer)	-0.007	0.11	-10000	0	-0.38	33	33
RAP1/GDP	-0.008	0.074	0.13	4	-0.22	9	13
KIDINS220/CRKL	0.027	0.006	-10000	0	-10000	0	0
BDNF (dimer)	0.017	0.062	-10000	0	-0.36	11	11
ubiquitin-dependent protein catabolic process	0.019	0.087	-10000	0	-0.24	40	40
Schwann cell development	-0.025	0.028	-10000	0	-10000	0	0
EHD4	0.027	0.006	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.061	0.026	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.027	0.033	-10000	0	-10000	0	0
RAP1B	0.027	0.007	-10000	0	-10000	0	0
RAP1A	0.027	0.005	-10000	0	-10000	0	0
CDC42/GTP	-0.046	0.14	-10000	0	-0.36	45	45
ABL1	0.027	0.006	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.04	0.008	-10000	0	-10000	0	0
Rap1/GTP	0.008	0.078	-10000	0	-0.44	4	4
STAT3	0.03	0.032	-10000	0	-0.28	4	4
axon guidance	-0.052	0.13	-10000	0	-0.35	45	45
MAPK3	-0.011	0.082	0.18	11	-0.22	43	54
MAPK1	-0.009	0.082	0.18	12	-0.23	41	53
CDC42/GDP	0	0.095	0.22	11	-0.26	11	22
NTF3	-0.007	0.11	-10000	0	-0.38	33	33
NTF4	0	0.092	-10000	0	-0.35	26	26
NGF (dimer)/TRKA/FAIM	0.023	0.088	-10000	0	-0.24	38	38
PI3K	0.036	0.014	-10000	0	-10000	0	0
FRS3	0.026	0.007	-10000	0	-10000	0	0
FAIM	0.026	0.021	-10000	0	-0.38	1	1
GAB1	0.027	0.006	-10000	0	-10000	0	0
RASGRF1	-0.09	0.15	-10000	0	-0.32	105	105
SOS1	0.028	0.003	-10000	0	-10000	0	0
MCF2L	-0.048	0.12	-10000	0	-0.25	94	94
RGS19	0.022	0.022	-10000	0	-0.35	1	1
CDC42	0.026	0.007	-10000	0	-10000	0	0
RAS family/GTP	0.012	0.099	0.27	7	-0.45	5	12
Rac1/GDP	-0.003	0.093	0.25	8	-0.26	11	19
NGF (dimer)/TRKA/GRIT	0.009	0.081	-10000	0	-0.24	39	39
neuron projection morphogenesis	-0.069	0.16	-10000	0	-0.82	4	4
NGF (dimer)/TRKA/NEDD4-2	0.019	0.087	-10000	0	-0.24	40	40
MAP2K1	0	0.052	0.2	24	-10000	0	24
NGFR	-0.1	0.19	-10000	0	-0.38	130	130
NGF (dimer)/TRKA/GIPC/GAIP	0.003	0.064	-10000	0	-0.28	6	6
RAS family/GTP/PI3K	0.02	0.012	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	0.071	0.031	-10000	0	-10000	0	0
NRAS	0.027	0.005	-10000	0	-10000	0	0
GRB2/SOS1	0.04	0.008	-10000	0	-10000	0	0
PRKCI	0.024	0.027	-10000	0	-0.35	2	2
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.026	0.008	-10000	0	-10000	0	0
PRKCZ	0.026	0.007	-10000	0	-10000	0	0
MAPKKK cascade	-0.066	0.2	-10000	0	-0.59	48	48
RASA1	0.025	0.008	-10000	0	-10000	0	0
TRKA/c-Abl	0.025	0.064	-10000	0	-0.27	18	18
SQSTM1	0.027	0.006	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	0.013	0.11	-10000	0	-0.21	62	62
NGF (dimer)/TRKA/p62/Atypical PKCs	0.04	0.085	-10000	0	-0.38	2	2
MATK	0.016	0.066	-10000	0	-0.38	11	11
NEDD4L	0.023	0.022	-10000	0	-0.38	1	1
RAS family/GDP	-0.028	0.049	-10000	0	-0.22	3	3
NGF (dimer)/TRKA	-0.085	0.15	-10000	0	-0.31	118	118
Rac1/GTP	-0.065	0.1	-10000	0	-0.25	65	65
FRS2 family/SHP2/CRK family	0.067	0.034	-10000	0	-10000	0	0

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.064	0.11	-10000	0	-0.28	5	5
NF kappa B1 p50/RelA/I kappa B alpha	-0.047	0.11	0.33	1	-0.28	3	4
alphaV/beta3 Integrin/Osteopontin/Src	-0.094	0.14	-10000	0	-0.24	194	194
AP1	-0.057	0.12	-10000	0	-0.37	7	7
ILK	-0.074	0.11	-10000	0	-0.31	3	3
bone resorption	-0.052	0.1	-10000	0	-0.32	3	3
PTK2B	0.025	0.009	-10000	0	-10000	0	0
PYK2/p130Cas	-0.042	0.12	-10000	0	-0.34	3	3
ITGAV	0.027	0.01	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.039	0.011	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.069	0.13	-10000	0	-0.21	186	186
MAP3K1	-0.075	0.1	0.19	3	-0.23	28	31
JUN	0.028	0.004	-10000	0	-10000	0	0
MAPK3	-0.076	0.1	0.23	5	-0.27	30	35
MAPK1	-0.075	0.1	0.19	4	-0.27	30	34
Rac1/GDP	0.019	0.006	-10000	0	-10000	0	0
NFKB1	0.027	0.005	-10000	0	-10000	0	0
MAPK8	-0.074	0.095	0.19	3	-0.3	3	6
ITGB3	0.024	0.043	-10000	0	-0.36	5	5
NFKBIA	-0.068	0.096	0.19	3	-0.27	29	32
FOS	0.006	0.091	-10000	0	-0.38	21	21
CD44	0.026	0.007	-10000	0	-10000	0	0
CHUK	0.027	0.006	-10000	0	-10000	0	0
PLAU	-0.072	0.13	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.049	0.12	-10000	0	-0.32	2	2
BCAR1	0.027	0.006	-10000	0	-10000	0	0
RELA	0.027	0.005	-10000	0	-10000	0	0
alphaV beta3 Integrin	0.037	0.035	-10000	0	-0.24	5	5
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	-0.076	0.11	0.19	5	-0.31	5	10
VAV3	-0.086	0.1	0.19	2	-0.33	14	16
MAP3K14	-0.075	0.11	0.19	5	-0.25	29	34
ROCK2	0.028	0.004	-10000	0	-10000	0	0
SPP1	-0.15	0.19	-10000	0	-0.35	195	195
RAC1	0.026	0.008	-10000	0	-10000	0	0
Rac1/GTP	-0.068	0.1	-10000	0	-0.31	13	13
MMP2	-0.061	0.096	0.31	1	-0.47	3	4

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0.032	0.082	-10000	0	-0.37	15	15
HDAC1	0.025	0.006	-10000	0	-10000	0	0
AES	0.026	0.007	-10000	0	-10000	0	0
FBXW11	0.027	0.006	-10000	0	-10000	0	0
DTX1	0.024	0.039	-10000	0	-0.37	4	4
LRP6/FZD1	0.035	0.016	-10000	0	-10000	0	0
TLE1	0.026	0.021	-10000	0	-0.39	1	1
AP1	-0.016	0.087	-10000	0	-0.24	44	44
NCSTN	0.027	0.005	-10000	0	-10000	0	0
ADAM10	0.027	0.005	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.006	0.17	-10000	0	-0.62	26	26
NICD/RBPSUH	0.03	0.083	-10000	0	-0.38	15	15
WIF1	-0.063	0.16	-10000	0	-0.38	86	86
NOTCH1	0.014	0.075	-10000	0	-0.39	13	13
PSENEN	0.027	0.007	-10000	0	-10000	0	0
KREMEN2	-0.049	0.15	-10000	0	-0.35	82	82
DKK1	-0.15	0.19	-10000	0	-0.36	186	186
beta catenin/beta TrCP1	0.037	0.077	0.25	4	-0.46	3	7
APH1B	0.027	0.005	-10000	0	-10000	0	0
APH1A	0.027	0.006	-10000	0	-10000	0	0
AXIN1	-0.011	0.092	-10000	0	-0.37	20	20
CtBP/CBP/TCF1/TLE1/AES	0.011	0.04	-10000	0	-10000	0	0
PSEN1	0.027	0.005	-10000	0	-10000	0	0
FOS	0.006	0.091	-10000	0	-0.38	21	21
JUN	0.028	0.004	-10000	0	-10000	0	0
MAP3K7	0.026	0.006	-10000	0	-10000	0	0
CTNNB1	0.024	0.079	0.25	4	-0.39	5	9
MAPK3	0.027	0.005	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.066	0.14	-10000	0	-0.22	171	171
HNF1A	0.017	0.061	-10000	0	-0.37	10	10
CTBP1	0.026	0.007	-10000	0	-10000	0	0
MYC	0.012	0.1	-10000	0	-1.1	3	3
NKD1	-0.02	0.13	-10000	0	-0.37	48	48
FZD1	0.025	0.009	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	0.029	0.084	-10000	0	-0.38	15	15
apoptosis	-0.015	0.087	-10000	0	-0.24	44	44
Delta 1/NOTCHprecursor	0.03	0.082	-10000	0	-0.37	15	15
DLL1	0.026	0.02	-10000	0	-0.35	1	1
PPARD	0.012	0.12	-10000	0	-0.85	7	7
Gamma Secretase	0.072	0.03	-10000	0	-10000	0	0
APC	-0.024	0.12	-10000	0	-0.39	31	31
DVL1	0.005	0.046	-10000	0	-0.43	2	2
CSNK2A1	0.025	0.009	-10000	0	-10000	0	0
MAP3K7IP1	-0.001	0.001	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.11	0.15	-10000	0	-0.23	226	226
LRP6	0.026	0.007	-10000	0	-10000	0	0
CSNK1A1	0.027	0.006	-10000	0	-10000	0	0
NLK	0.012	0.005	-10000	0	-10000	0	0
CCND1	0.014	0.097	-10000	0	-0.88	4	4
WNT1	0.006	0.09	-10000	0	-0.38	21	21
Axin1/APC/beta catenin	0.015	0.12	0.32	4	-0.41	14	18
DKK2	-0.075	0.17	-10000	0	-0.35	111	111
NOTCH1 precursor/DVL1	0.015	0.11	-10000	0	-0.57	9	9
GSK3B	0.027	0.005	-10000	0	-10000	0	0
FRAT1	0.026	0.006	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	0.031	0.084	-10000	0	-0.38	15	15
PPP2R5D	0.033	0.06	0.23	25	-0.29	1	26
MAPK1	0.027	0.006	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.002	0.11	-10000	0	-0.22	72	72
RBPJ	0.027	0.005	-10000	0	-10000	0	0
CREBBP	0.028	0.008	-10000	0	-10000	0	0

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.038	0.064	-10000	0	-0.21	23	23
NF kappa B1 p50/RelA/I kappa B alpha	-0.006	0.098	0.3	1	-0.36	5	6
AP1	-0.026	0.093	-10000	0	-0.33	8	8
mol:PIP3	-0.022	0.076	-10000	0	-0.35	6	6
AKT1	0.021	0.073	0.27	8	-0.31	2	10
PTK2B	-0.016	0.083	0.2	1	-0.28	22	23
RHOA	0.005	0.063	0.21	7	-0.34	8	15
PIK3CB	0.027	0.006	-10000	0	-10000	0	0
mol:Ca2+	-0.015	0.073	0.21	5	-0.34	4	9
MAGI3	0.027	0.005	-10000	0	-10000	0	0
RELA	0.027	0.005	-10000	0	-10000	0	0
apoptosis	-0.023	0.094	-10000	0	-0.23	62	62
HRAS/GDP	0.02	0.005	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.047	0.11	0.21	12	-0.33	24	36
NF kappa B1 p50/RelA	-0.032	0.092	-10000	0	-0.36	7	7
endothelial cell migration	0.004	0.063	-10000	0	-0.24	23	23
ADCY4	-0.039	0.13	-10000	0	-0.39	35	35
ADCY5	-0.08	0.18	-10000	0	-0.44	71	71
ADCY6	-0.038	0.12	-10000	0	-0.39	34	34
ADCY7	-0.039	0.13	-10000	0	-0.39	35	35
ADCY1	-0.042	0.12	-10000	0	-0.39	34	34
ADCY2	-0.061	0.16	-10000	0	-0.42	53	53
ADCY3	-0.039	0.12	-10000	0	-0.39	35	35
ADCY8	-0.038	0.12	-10000	0	-0.38	33	33
ADCY9	-0.042	0.13	-10000	0	-0.39	39	39
GSK3B	-0.013	0.085	0.19	11	-0.29	17	28
arachidonic acid secretion	-0.049	0.13	-10000	0	-0.38	41	41
GNG2	0.026	0.019	-10000	0	-0.35	1	1
TRIP6	0.018	0.01	-10000	0	-10000	0	0
GNAO1	-0.039	0.12	-10000	0	-0.25	85	85
HRAS	0.026	0.007	-10000	0	-10000	0	0
NFKBIA	-0.025	0.095	0.3	1	-0.36	7	8
GAB1	0.027	0.006	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	-0.024	0.23	-10000	0	-0.78	35	35
JUN	0.027	0.004	-10000	0	-10000	0	0
LPA/LPA2/NHERF2	0.036	0.012	-10000	0	-10000	0	0
TIAM1	-0.046	0.27	-10000	0	-0.92	35	35
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
mol:IP3	-0.016	0.065	0.21	5	-0.27	2	7
PLCB3	0.017	0.02	0.19	5	-10000	0	5
FOS	0.006	0.091	-10000	0	-0.38	21	21
positive regulation of mitosis	-0.049	0.13	-10000	0	-0.38	41	41
LPA/LPA1-2-3	0.009	0.1	-10000	0	-0.21	65	65
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0	-10000	0	-10000	0	0
BCAR1	0.027	0.006	-10000	0	-10000	0	0
stress fiber formation	-0.009	0.087	0.23	2	-0.32	16	18
GNAZ	-0.011	0.081	-10000	0	-0.23	48	48
EGFR/PI3K-beta/Gab1	-0.011	0.084	-10000	0	-0.36	6	6
positive regulation of dendritic cell cytokine production	0.008	0.098	-10000	0	-0.21	65	65
LPA/LPA2/MAGI-3	0.037	0.012	-10000	0	-10000	0	0
ARHGEF1	0.02	0.073	0.2	30	-0.36	1	31
GNAI2	0.004	0.058	-10000	0	-0.23	23	23
GNAI3	0.005	0.057	-10000	0	-0.23	22	22
GNAI1	0.001	0.07	-10000	0	-0.26	25	25
LPA/LPA3	-0.014	0.092	-10000	0	-0.26	50	50
LPA/LPA2	0.021	0.007	-10000	0	-10000	0	0
LPA/LPA1	0.008	0.07	-10000	0	-0.27	24	24
HB-EGF/EGFR	-0.031	0.096	-10000	0	-0.21	90	90
HBEGF	-0.047	0.11	-10000	0	-0.25	91	91
mol:DAG	-0.016	0.065	0.21	5	-0.27	2	7
cAMP biosynthetic process	-0.059	0.15	0.34	3	-0.41	40	43
NFKB1	0.027	0.005	-10000	0	-10000	0	0
SRC	0.024	0.01	-10000	0	-10000	0	0
GNB1	0.026	0.007	-10000	0	-10000	0	0
LYN	-0.019	0.1	0.3	4	-0.35	9	13
GNAQ	-0.009	0.07	-10000	0	-0.21	41	41
LPAR2	0.027	0.005	-10000	0	-10000	0	0
LPAR3	-0.026	0.13	-10000	0	-0.38	50	50
LPAR1	0.006	0.096	-10000	0	-0.39	23	23
IL8	-0.11	0.14	-10000	0	-0.36	35	35
PTK2	-0.019	0.076	0.18	2	-0.36	3	5
Rac1/GDP	0.019	0.006	-10000	0	-10000	0	0
CASP3	-0.023	0.094	-10000	0	-0.23	62	62
EGFR	0.017	0.057	-10000	0	-0.38	8	8
PLCG1	-0.015	0.072	0.16	1	-0.22	43	44
PLD2	-0.02	0.083	0.18	5	-0.36	4	9
G12/G13	0.037	0.063	-10000	0	-0.21	21	21
PI3K-beta	0.006	0.056	-10000	0	-0.33	3	3
cell migration	-0.003	0.081	-10000	0	-0.24	30	30
SLC9A3R2	0.027	0.006	-10000	0	-10000	0	0
PXN	-0.009	0.088	0.23	2	-0.32	16	18
HRAS/GTP	-0.049	0.14	-10000	0	-0.39	39	39
RAC1	0.026	0.008	-10000	0	-10000	0	0
MMP9	-0.063	0.16	-10000	0	-0.35	92	92
PRKCE	0.027	0.004	-10000	0	-10000	0	0
PRKCD	-0.02	0.074	0.2	5	-0.35	5	10
Gi(beta/gamma)	-0.035	0.12	-10000	0	-0.36	36	36
mol:LPA	0.002	0.007	-10000	0	-10000	0	0
TRIP6/p130 Cas/FAK1/Paxillin	0.006	0.093	-10000	0	-0.32	8	8
MAPKKK cascade	-0.049	0.13	-10000	0	-0.38	41	41
contractile ring contraction involved in cytokinesis	0.005	0.069	0.21	7	-0.33	9	16
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.013	0.075	-10000	0	-0.21	47	47
GNA15	-0.011	0.074	-10000	0	-0.22	45	45
GNA12	0.026	0.008	-10000	0	-10000	0	0
GNA13	0.027	0.005	-10000	0	-10000	0	0
MAPT	-0.048	0.12	0.21	12	-0.34	24	36
GNA11	-0.01	0.071	-10000	0	-0.22	41	41
Rac1/GTP	-0.026	0.24	-10000	0	-0.82	35	35
MMP2	0.004	0.063	-10000	0	-0.24	23	23

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	0.015	0.066	-10000	0	-0.22	29	29
EFNA5	0.008	0.084	-10000	0	-0.38	18	18
FYN	-0.003	0.056	0.18	3	-0.2	28	31
neuron projection morphogenesis	0.015	0.066	-10000	0	-0.22	29	29
cell-cell signaling	0	0	-10000	0	-10000	0	0
Ephrin A5/EPHA5	0.015	0.066	-10000	0	-0.22	29	29
EPHA5	0.016	0.064	-10000	0	-0.37	11	11

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.029	0.12	0.31	33	-10000	0	33
GNAI2	0.027	0.005	-10000	0	-10000	0	0
S1P/S1P5/G12	0.029	0.037	-10000	0	-0.2	9	9
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.055	0.16	-10000	0	-0.38	82	82
RhoA/GTP	-0.03	0.12	-10000	0	-0.32	31	31
negative regulation of cAMP metabolic process	-0.035	0.12	-10000	0	-0.25	77	77
GNAZ	0.001	0.1	-10000	0	-0.38	26	26
GNAI3	0.027	0.005	-10000	0	-10000	0	0
GNA12	0.026	0.008	-10000	0	-10000	0	0
S1PR5	0.017	0.062	-10000	0	-0.35	11	11
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.035	0.12	-10000	0	-0.25	77	77
RhoA/GDP	0.02	0.004	-10000	0	-10000	0	0
RHOA	0.027	0.006	-10000	0	-10000	0	0
GNAI1	0.02	0.054	-10000	0	-0.38	7	7

×

Visual signal transduction: Rods

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
mol:K +	0.027	0.004	-10000	0	-10000	0	0
GNAT1/GTP	0.01	0.04	-10000	0	-0.24	10	10
Metarhodopsin II/Arrestin	0.024	0.034	-10000	0	-0.24	6	6
PDE6G/GNAT1/GTP	0.02	0.054	-10000	0	-0.21	22	22
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	0.013	0.058	-10000	0	-0.35	10	10
GRK1	0.015	0.041	-10000	0	-0.35	5	5
CNG Channel	-0.001	0.1	-10000	0	-0.34	14	14
mol:Na +	0.001	0.095	-10000	0	-0.34	8	8
mol:ADP	0.015	0.041	-10000	0	-0.35	5	5
RGS9-1/Gbeta5/R9AP	-0.023	0.13	-10000	0	-0.25	101	101
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	0.009	0.1	-10000	0	-0.35	8	8
CNGB1	0.007	0.082	-10000	0	-0.36	20	20
RDH5	0.022	0.045	-10000	0	-0.38	5	5
SAG	0.02	0.019	-10000	0	-0.35	1	1
mol:Ca2+	-0.024	0.12	0.35	26	-0.33	8	34
Na + (4 Units)	-0.003	0.089	-10000	0	-0.32	8	8
RGS9	-0.058	0.17	-10000	0	-0.38	85	85
GNB1/GNGT1	0.009	0.078	-10000	0	-0.24	35	35
GNAT1/GDP	-0.017	0.12	-10000	0	-0.22	107	107
GUCY2D	0.013	0.064	-10000	0	-0.35	12	12
GNGT1	-0.011	0.1	-10000	0	-0.35	35	35
GUCY2F	0.02	0.004	-10000	0	-10000	0	0
GNB5	0.027	0.005	-10000	0	-10000	0	0
mol:GMP (4 units)	-0.003	0.076	-10000	0	-0.22	41	41
mol:11-cis-retinal	0.022	0.045	-10000	0	-0.38	5	5
mol:cGMP	0.022	0.072	-10000	0	-0.34	2	2
GNB1	0.026	0.007	-10000	0	-10000	0	0
Rhodopsin	0.028	0.046	-10000	0	-0.26	10	10
SLC24A1	0.028	0.004	-10000	0	-10000	0	0
CNGA1	0.002	0.098	-10000	0	-0.38	25	25
Metarhodopsin II	0.019	0.039	-10000	0	-0.22	9	9
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.032	0.078	-10000	0	-0.21	26	26
RGS9BP	-0.011	0.12	-10000	0	-0.38	37	37
Metarhodopsin II/Transducin	-0.004	0.053	-10000	0	-0.24	13	13
GCAP Family/Ca ++	0.027	0.063	-10000	0	-0.19	30	30
PDE6A/B	0.015	0.08	-10000	0	-0.26	30	30
mol:Pi	-0.024	0.13	-10000	0	-0.25	101	101
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	0.016	0.074	-10000	0	-0.2	41	41
PDE6B	0.013	0.072	-10000	0	-0.37	14	14
PDE6A	0.009	0.082	-10000	0	-0.36	19	19
PDE6G	0.016	0.065	-10000	0	-0.36	12	12
RHO	0.016	0.045	-10000	0	-0.35	6	6
PDE6	-0.019	0.14	-10000	0	-0.36	25	25
GUCA1A	0.001	0.092	-10000	0	-0.35	26	26
GC2/GCAP Family	0.037	0.068	-10000	0	-0.2	20	20
GUCA1C	0.018	0.027	-10000	0	-0.37	2	2
GUCA1B	0.024	0.028	-10000	0	-0.37	2	2

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.046	0.061	-10000	0	-0.19	22	22
ER alpha/Gai/GDP/Gbeta gamma	-0.072	0.2	-10000	0	-0.52	47	47
AKT1	-0.02	0.2	-10000	0	-0.78	25	25
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.018	0.2	-10000	0	-0.79	25	25
mol:Ca2+	0.012	0.076	0.18	28	-0.32	9	37
IGF1R	0.025	0.028	-10000	0	-0.37	2	2
E2/ER alpha (dimer)/Striatin	0.026	0.049	-10000	0	-0.22	15	15
SHC1	0.027	0.005	-10000	0	-10000	0	0
apoptosis	0.018	0.19	0.74	25	-10000	0	25
RhoA/GTP	0.016	0.036	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.02	0.17	0.21	1	-0.44	36	37
regulation of stress fiber formation	-0.005	0.063	-10000	0	-0.19	8	8
E2/ERA-ERB (dimer)	0.022	0.057	-10000	0	-0.22	22	22
KRAS	0.025	0.009	-10000	0	-10000	0	0
G13/GTP	0.025	0.045	-10000	0	-0.2	15	15
pseudopodium formation	0.005	0.063	0.19	8	-10000	0	8
E2/ER alpha (dimer)/PELP1	0.025	0.049	-10000	0	-0.22	15	15
GRB2	0.027	0.005	-10000	0	-10000	0	0
GNG2	0.027	0.019	-10000	0	-0.35	1	1
GNAO1	-0.055	0.16	-10000	0	-0.38	82	82
HRAS	0.026	0.007	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.039	0.18	0.21	2	-0.54	31	33
E2/ER beta (dimer)	0.015	0.037	-10000	0	-0.24	8	8
mol:GDP	0.004	0.065	-10000	0	-0.32	12	12
mol:NADP	-0.039	0.18	0.21	2	-0.54	31	33
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
mol:IP3	0	0.063	0.16	3	-0.32	10	13
IGF-1R heterotetramer	0.025	0.028	-10000	0	-0.37	2	2
PLCB1	0.007	0.057	-10000	0	-0.34	8	8
PLCB2	0.007	0.059	-10000	0	-0.34	8	8
IGF1	-0.022	0.13	-10000	0	-0.37	51	51
mol:L-citrulline	-0.039	0.18	0.21	2	-0.54	31	33
RHOA	0.027	0.006	-10000	0	-10000	0	0
Gai/GDP	-0.13	0.3	-10000	0	-0.63	104	104
JNK cascade	0.015	0.036	-10000	0	-0.24	8	8
BCAR1	0.027	0.006	-10000	0	-10000	0	0
ESR2	0.02	0.053	-10000	0	-0.35	8	8
GNAQ	0.027	0.006	-10000	0	-10000	0	0
ESR1	0.012	0.077	-10000	0	-0.38	15	15
Gq family/GDP/Gbeta gamma	-0.018	0.18	-10000	0	-0.67	25	25
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.018	0.1	-10000	0	-0.76	5	5
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.018	0.17	0.21	1	-0.44	35	36
GNAZ	0.001	0.1	-10000	0	-0.38	26	26
E2/ER alpha (dimer)	0.009	0.054	-10000	0	-0.27	15	15
STRN	0.028	0.004	-10000	0	-10000	0	0
GNAL	-0.001	0.1	-10000	0	-0.38	27	27
PELP1	0.026	0.007	-10000	0	-10000	0	0
MAPK11	0.009	0.03	-10000	0	-0.2	8	8
GNAI2	0.027	0.005	-10000	0	-10000	0	0
GNAI3	0.027	0.005	-10000	0	-10000	0	0
GNAI1	0.02	0.054	-10000	0	-0.38	7	7
HBEGF	-0.04	0.21	0.32	35	-0.46	45	80
cAMP biosynthetic process	0.005	0.072	-10000	0	-0.2	43	43
SRC	-0.048	0.19	0.21	28	-0.5	42	70
PI3K	0.036	0.014	-10000	0	-10000	0	0
GNB1	0.026	0.007	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	0.03	0.07	-10000	0	-0.28	13	13
SOS1	0.028	0.003	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.052	0.13	-10000	0	-0.38	39	39
Gs family/GTP	0.011	0.075	-10000	0	-0.2	43	43
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.044	0.021	-10000	0	-10000	0	0
vasodilation	-0.037	0.16	0.21	2	-0.51	31	33
mol:DAG	0	0.063	0.16	3	-0.32	10	13
Gs family/GDP/Gbeta gamma	0	0.079	-10000	0	-0.33	13	13
MSN	0.005	0.065	0.2	8	-10000	0	8
Gq family/GTP	0.015	0.06	-10000	0	-0.36	8	8
mol:PI-3-4-5-P3	-0.016	0.19	-10000	0	-0.75	25	25
NRAS	0.027	0.005	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.037	0.16	0.51	31	-0.21	2	33
GRB2/SOS1	0.04	0.008	-10000	0	-10000	0	0
RhoA/GDP	0.017	0.069	-10000	0	-0.31	12	12
NOS3	-0.043	0.19	0.22	1	-0.58	31	32
GNA11	0.026	0.007	-10000	0	-10000	0	0
MAPKKK cascade	-0.009	0.17	0.28	5	-0.58	25	30
E2/ER alpha (dimer)/PELP1/Src	-0.021	0.18	0.25	8	-0.46	36	44
ruffle organization	0.005	0.063	0.19	8	-10000	0	8
ROCK2	0.01	0.072	0.21	10	-10000	0	10
GNA14	0.02	0.053	-10000	0	-0.38	7	7
GNA15	0.022	0.042	-10000	0	-0.35	5	5
GNA13	0.027	0.005	-10000	0	-10000	0	0
MMP9	-0.059	0.21	0.32	38	-0.45	52	90
MMP2	-0.04	0.19	0.28	12	-0.49	38	50

×

S1P4 pathway

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
mol:S1P	0	0	-10000	0	-10000	0	0
GNAO1	-0.055	0.16	-10000	0	-0.38	82	82
CDC42/GTP	-0.031	0.12	-10000	0	-0.31	33	33
PLCG1	-0.032	0.1	-10000	0	-0.34	22	22
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.027	0.005	-10000	0	-10000	0	0
GNAI3	0.027	0.005	-10000	0	-10000	0	0
G12/G13	0.038	0.013	-10000	0	-10000	0	0
cell migration	-0.031	0.12	-10000	0	-0.3	33	33
S1PR5	0.017	0.062	-10000	0	-0.35	11	11
S1PR4	0.023	0.038	-10000	0	-0.35	4	4
MAPK3	-0.038	0.11	-10000	0	-0.34	25	25
MAPK1	-0.036	0.11	-10000	0	-0.35	23	23
S1P/S1P5/Gi	-0.035	0.12	-10000	0	-0.25	77	77
GNAI1	0.02	0.054	-10000	0	-0.38	7	7
CDC42/GDP	0.02	0.005	-10000	0	-10000	0	0
S1P/S1P5/G12	0.029	0.037	-10000	0	-0.2	9	9
RHOA	0.023	0.05	0.19	29	-10000	0	29
S1P/S1P4/Gi	-0.035	0.12	-10000	0	-0.25	76	76
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	0.001	0.1	-10000	0	-0.38	26	26
S1P/S1P4/G12/G13	0.044	0.03	-10000	0	-0.19	4	4
GNA12	0.026	0.008	-10000	0	-10000	0	0
GNA13	0.027	0.005	-10000	0	-10000	0	0
CDC42	0.026	0.007	-10000	0	-10000	0	0

×

Arf6 signaling events

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
CENTA1/KIF3B	0.03	0.022	-10000	0	-0.2	2	2
ARNO/beta Arrestin1-2	-0.03	0.16	-10000	0	-0.81	11	11
EGFR	0.017	0.057	-10000	0	-0.38	8	8
EPHA2	0.021	0.047	-10000	0	-0.36	6	6
USP6	0.022	0.039	-10000	0	-0.37	4	4
IQSEC1	0.028	0.004	-10000	0	-10000	0	0
EGFR/EGFR/EGF/EGF	0.001	0.093	-10000	0	-0.25	48	48
ARRB2	0.009	0.019	-10000	0	-10000	0	0
mol:GTP	0.014	0.041	0.14	16	-0.14	2	18
ARRB1	0.027	0.005	-10000	0	-10000	0	0
FBXO8	0.026	0.007	-10000	0	-10000	0	0
TSHR	0.013	0.075	-10000	0	-0.38	14	14
EGF	-0.016	0.12	-10000	0	-0.36	44	44
somatostatin receptor activity	0	0	0.001	10	-0.001	27	37
ARAP2	0.027	0.005	-10000	0	-10000	0	0
mol:GDP	-0.046	0.12	0.23	3	-0.27	54	57
mol:PI-3-4-5-P3	0	0	0.001	3	-0.001	8	11
ITGA2B	0.015	0.067	-10000	0	-0.36	13	13
ARF6	0.027	0.006	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.059	0.039	-10000	0	-0.19	6	6
ADAP1	0.024	0.028	-10000	0	-0.35	2	2
KIF13B	0.025	0.009	-10000	0	-10000	0	0
HGF/MET	0.014	0.082	-10000	0	-0.26	33	33
PXN	0.027	0.005	-10000	0	-10000	0	0
ARF6/GTP	-0.032	0.11	0.23	10	-0.27	29	39
EGFR/EGFR/EGF/EGF/ARFGEP100	0.017	0.086	-10000	0	-0.21	48	48
ADRB2	-0.079	0.18	-10000	0	-0.38	106	106
receptor agonist activity	0	0	0	8	0	28	36
actin filament binding	0	0	0.001	9	0	32	41
SRC	0.024	0.01	-10000	0	-10000	0	0
ITGB3	0.023	0.042	-10000	0	-0.36	5	5
GNAQ	0.027	0.006	-10000	0	-10000	0	0
EFA6/PI-4-5-P2	0	0.001	0.001	15	-0.001	19	34
ARF6/GDP	-0.017	0.14	0.22	5	-0.45	26	31
ARF6/GDP/GULP/ACAP1	-0.029	0.13	0.23	3	-0.32	35	38
alphaIIb/beta3 Integrin/paxillin/GIT1	0.057	0.056	-10000	0	-0.19	18	18
ACAP1	0.017	0.06	-10000	0	-0.36	10	10
ACAP2	0.026	0.007	-10000	0	-10000	0	0
LHCGR/beta Arrestin2	0.014	0.033	-10000	0	-0.2	6	6
EFNA1	0.026	0.019	-10000	0	-0.35	1	1
HGF	0.014	0.07	-10000	0	-0.37	13	13
CYTH3	0.006	0.002	-10000	0	-10000	0	0
CYTH2	-0.007	0.16	-10000	0	-1	11	11
NCK1	0.027	0.005	-10000	0	-10000	0	0
fibronectin binding	0	0	0.001	8	0	23	31
endosomal lumen acidification	0	0	0.001	26	0	13	39
microtubule-based process	0	0	-10000	0	0	1	1
GULP1	0.014	0.072	-10000	0	-0.38	13	13
GNAQ/ARNO	0.009	0.15	-10000	0	-0.92	11	11
mol:Phosphatidic acid	0	0	0	2	-10000	0	2
PIP3-E	0	0	0	3	0	4	7
MET	0.005	0.088	-10000	0	-0.36	23	23
GNA14	0.02	0.053	-10000	0	-0.38	7	7
GNA15	0.022	0.042	-10000	0	-0.35	5	5
GIT1	0.028	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	0.001	12	-0.001	25	37
GNA11	0.026	0.007	-10000	0	-10000	0	0
LHCGR	0.017	0.046	-10000	0	-0.35	6	6
AGTR1	-0.075	0.18	-10000	0	-0.38	102	102
desensitization of G-protein coupled receptor protein signaling pathway	0.014	0.033	-10000	0	-0.2	6	6
IPCEF1/ARNO	-0.005	0.15	-10000	0	-0.86	11	11
alphaIIb/beta3 Integrin	0.028	0.06	-10000	0	-0.25	18	18

×

Integrins in angiogenesis

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.037	0.019	-10000	0	-0.25	1	1
alphaV beta3 Integrin	0.036	0.065	-10000	0	-0.22	23	23
PTK2	0.01	0.12	0.29	25	-0.35	5	30
IGF1R	0.025	0.028	-10000	0	-0.37	2	2
PI4KB	0.027	0.006	-10000	0	-10000	0	0
MFGE8	0.027	0.006	-10000	0	-10000	0	0
SRC	0.024	0.01	-10000	0	-10000	0	0
CDKN1B	-0.042	0.14	-10000	0	-0.42	45	45
VEGFA	0.025	0.02	-10000	0	-0.35	1	1
ILK	-0.042	0.14	-10000	0	-0.41	45	45
ROCK1	0.027	0.006	-10000	0	-10000	0	0
AKT1	-0.043	0.13	-10000	0	-0.39	43	43
PTK2B	0	0.054	0.19	23	-10000	0	23
alphaV/beta3 Integrin/JAM-A	-0.001	0.11	-10000	0	-0.23	48	48
CBL	0.027	0.006	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.033	0.07	-10000	0	-0.22	29	29
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.033	0.09	-10000	0	-0.2	49	49
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.007	0.07	-10000	0	-0.29	6	6
alphaV/beta3 Integrin/Syndecan-1	0.047	0.04	-10000	0	-0.21	8	8
PI4KA	0.027	0.006	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.005	0.12	-10000	0	-0.35	18	18
PI4 Kinase	0.038	0.013	-10000	0	-10000	0	0
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.074	0.13	-10000	0	-0.21	197	197
RPS6KB1	-0.045	0.1	0.24	3	-0.34	18	21
TLN1	0.026	0.008	-10000	0	-10000	0	0
MAPK3	-0.041	0.13	-10000	0	-0.5	20	20
GPR124	0.025	0.009	-10000	0	-10000	0	0
MAPK1	-0.043	0.13	-10000	0	-0.48	22	22
PXN	0.027	0.005	-10000	0	-10000	0	0
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	0.008	0.1	-10000	0	-0.22	67	67
cell adhesion	0.03	0.058	-10000	0	-0.2	11	11
ANGPTL3	0.001	0.096	-10000	0	-0.37	26	26
VEGFR2 homodimer/VEGFA homodimer/Src	0.044	0.027	-10000	0	-0.21	1	1
IGF-1R heterotetramer	0.025	0.028	-10000	0	-0.37	2	2
Rac1/GDP	0.019	0.006	-10000	0	-10000	0	0
TGFBR2	0.027	0.005	-10000	0	-10000	0	0
ITGB3	0.023	0.042	-10000	0	-0.36	5	5
IGF1	-0.022	0.13	-10000	0	-0.37	51	51
RAC1	0.026	0.008	-10000	0	-10000	0	0
regulation of cell-matrix adhesion	0.044	0.035	-10000	0	-0.21	5	5
apoptosis	0.026	0.007	-10000	0	-10000	0	0
CD47	0.028	0.004	-10000	0	-10000	0	0
alphaV/beta3 Integrin/CD47	0.049	0.033	-10000	0	-0.21	5	5
VCL	0.026	0.007	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Del1	0.042	0.049	-10000	0	-0.24	10	10
CSF1	0.026	0.019	-10000	0	-0.35	1	1
PIK3C2A	-0.042	0.14	-10000	0	-0.41	45	45
PI4 Kinase/Pyk2	-0.012	0.092	-10000	0	-0.32	8	8
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.057	0.04	-10000	0	-0.19	6	6
FAK1/Vinculin	0.021	0.11	0.28	25	-0.32	3	28
alphaV beta3/Integrin/ppsTEM5	0.044	0.035	-10000	0	-0.21	5	5
RHOA	0.027	0.006	-10000	0	-10000	0	0
VTN	-0.051	0.16	-10000	0	-0.37	81	81
BCAR1	0.027	0.006	-10000	0	-10000	0	0
FGF2	0.009	0.084	-10000	0	-0.38	18	18
F11R	0.002	0.053	-10000	0	-0.27	15	15
alphaV/beta3 Integrin/Lactadherin	0.048	0.034	-10000	0	-0.21	5	5
alphaV/beta3 Integrin/TGFBR2	0.048	0.033	-10000	0	-0.21	5	5
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.061	0.029	-10000	0	-0.19	1	1
HSP90AA1	0.025	0.027	-10000	0	-0.35	2	2
alphaV/beta3 Integrin/Talin	0.044	0.032	-10000	0	-0.19	5	5
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	-0.01	0.11	-10000	0	-0.35	41	41
alphaV/beta3 Integrin/Pyk2	0.046	0.047	-10000	0	-10000	0	0
SDC1	0.024	0.035	-10000	0	-0.38	3	3
VAV3	-0.017	0.052	0.18	10	-10000	0	10
PTPN11	0.028	0.004	-10000	0	-10000	0	0
IRS1	0.027	0.021	-10000	0	-0.38	1	1
FAK1/Paxillin	0.022	0.11	0.27	26	-0.32	3	29
cell migration	0.016	0.1	0.25	31	-0.29	3	34
ITGAV	0.026	0.007	-10000	0	-10000	0	0
PI3K	0.01	0.11	-10000	0	-0.34	9	9
SPP1	-0.15	0.19	-10000	0	-0.35	195	195
KDR	0.027	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.026	0.007	-10000	0	-10000	0	0
COL4A3	-0.033	0.14	-10000	0	-0.37	63	63
angiogenesis	-0.05	0.14	-10000	0	-0.48	25	25
Rac1/GTP	0.018	0.051	-10000	0	-10000	0	0
EDIL3	0.02	0.05	-10000	0	-0.38	6	6
cell proliferation	0.048	0.033	-10000	0	-0.21	5	5

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.006	0.001	-10000	0	-10000	0	0
ADCY5	-0.053	0.09	-10000	0	-0.23	88	88
ADCY6	-0.006	0.001	-10000	0	-10000	0	0
ADCY7	-0.006	0.002	-10000	0	-10000	0	0
ADCY1	-0.012	0.035	-10000	0	-0.2	13	13
ADCY2	-0.035	0.075	-10000	0	-0.22	56	56
ADCY3	-0.006	0.001	-10000	0	-10000	0	0
ADCY8	-0.01	0.02	-10000	0	-0.2	4	4
PRKCE	0.007	0.001	-10000	0	-10000	0	0
ADCY9	-0.007	0.015	-10000	0	-0.23	2	2
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	0	0.084	0.22	22	-0.24	2	24

×

ErbB4 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.026	0.06	-10000	0	-10000	0	0
epithelial cell differentiation	0.018	0.076	-10000	0	-10000	0	0
ITCH	0.029	0.017	-10000	0	-10000	0	0
WWP1	0.017	0.062	-10000	0	-10000	0	0
FYN	0.027	0.005	-10000	0	-10000	0	0
EGFR	0.017	0.057	-10000	0	-0.38	8	8
PRL	0.01	0.068	-10000	0	-0.35	14	14
neuron projection morphogenesis	-0.007	0.1	0.29	20	-10000	0	20
PTPRZ1	-0.11	0.19	-10000	0	-0.38	133	133
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.003	0.1	-10000	0	-10000	0	0
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.026	0.091	-10000	0	-0.29	10	10
ADAM17	0.031	0.014	-10000	0	-10000	0	0
ErbB4/ErbB4	0.012	0.054	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	0.006	0.09	-10000	0	-0.34	6	6
NCOR1	0.026	0.008	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.014	0.094	-10000	0	-0.31	1	1
GRIN2B	-0.029	0.1	0.25	9	-0.33	3	12
ErbB4/ErbB2/betacellulin	0.018	0.068	-10000	0	-0.43	2	2
STAT1	0.018	0.059	-10000	0	-0.35	10	10
HBEGF	0.026	0.021	-10000	0	-0.38	1	1
PRLR	-0.01	0.12	-10000	0	-0.38	36	36
E4ICDs/ETO2	0.016	0.073	-10000	0	-0.31	3	3
axon guidance	0.035	0.08	0.31	7	-10000	0	7
NEDD4	0.031	0.015	-10000	0	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	0	0.096	-10000	0	-0.27	45	45
CBFA2T3	0	0.1	-10000	0	-0.38	26	26
ErbB4/ErbB2/HBEGF	0.024	0.05	-10000	0	-0.32	1	1
MAPK3	-0.004	0.11	0.3	16	-10000	0	16
STAT1 (dimer)	0.022	0.068	-10000	0	-10000	0	0
MAPK1	-0.002	0.11	0.3	16	-10000	0	16
JAK2	0.024	0.01	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.019	0.092	-10000	0	-0.3	12	12
NRG1	-0.042	0.11	-10000	0	-0.27	79	79
NRG3	-0.019	0.13	-10000	0	-0.38	45	45
NRG2	-0.099	0.19	-10000	0	-0.38	125	125
NRG4	-0.11	0.19	-10000	0	-0.38	135	135
heart development	0.035	0.08	0.31	7	-10000	0	7
neural crest cell migration	-0.018	0.092	-10000	0	-0.29	12	12
ERBB2	0.01	0.031	-10000	0	-0.28	4	4
WWOX/E4ICDs	0.021	0.048	-10000	0	-10000	0	0
SHC1	0.027	0.005	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.034	0.12	-10000	0	-0.31	18	18
apoptosis	0.019	0.12	0.37	29	-10000	0	29
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.034	0.12	-10000	0	-0.32	14	14
ErbB4/ErbB2/epiregulin	-0.016	0.094	-10000	0	-0.33	3	3
ErbB4/ErbB4/betacellulin/betacellulin	0.017	0.08	-10000	0	-0.33	4	4
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.025	0.094	-10000	0	-0.32	1	1
MDM2	0.014	0.062	0.26	12	-10000	0	12
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.017	0.086	-10000	0	-0.28	1	1
STAT5A	0.037	0.083	0.29	11	-10000	0	11
ErbB4/EGFR/neuregulin 1 beta	-0.017	0.096	-10000	0	-0.33	6	6
DLG4	0.026	0.008	-10000	0	-10000	0	0
GRB2/SHC	0.039	0.01	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	0.024	0.053	-10000	0	-10000	0	0
STAT5A (dimer)	0.034	0.094	0.29	2	-10000	0	2
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.055	0.085	0.32	5	-10000	0	5
LRIG1	0.026	0.021	-10000	0	-0.38	1	1
EREG	-0.09	0.18	-10000	0	-0.35	127	127
BTC	0.003	0.098	-10000	0	-0.38	25	25
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.028	0.074	0.31	7	-10000	0	7
ERBB4	0.004	0.043	-10000	0	-10000	0	0
STAT5B	0.027	0.005	-10000	0	-10000	0	0
YAP1	0.019	0.068	-10000	0	-0.39	8	8
GRB2	0.027	0.005	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.029	0.1	-10000	0	-0.38	4	4
glial cell differentiation	-0.024	0.053	-10000	0	-10000	0	0
WWOX	0.019	0.013	-10000	0	-10000	0	0
cell proliferation	-0.013	0.13	0.32	9	-0.45	5	14

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.029	0.083	0.23	12	-0.32	3	15
PDGFB-D/PDGFRB/SLAP	0.017	0.069	-10000	0	-0.24	26	26
PDGFB-D/PDGFRB/APS/CBL	0.034	0.064	-10000	0	-0.2	25	25
AKT1	0.032	0.1	0.28	26	-10000	0	26
mol:PI-4-5-P2	0	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.048	0.1	0.26	27	-0.37	3	30
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
FGR	0.008	0.1	0.35	2	-0.44	12	14
mol:Ca2+	0.041	0.1	0.25	27	-0.38	5	32
MYC	0.082	0.15	0.4	32	-0.74	2	34
SHC1	0.027	0.005	-10000	0	-10000	0	0
HRAS/GDP	0.036	0.073	-10000	0	-10000	0	0
LRP1/PDGFRB/PDGFB	0.035	0.069	-10000	0	-0.22	26	26
GRB10	0.026	0.02	-10000	0	-0.35	1	1
PTPN11	0.028	0.004	-10000	0	-10000	0	0
GO:0007205	0.04	0.1	0.25	27	-0.38	5	32
PTEN	0.026	0.008	-10000	0	-10000	0	0
GRB2	0.027	0.005	-10000	0	-10000	0	0
GRB7	0.019	0.044	-10000	0	-0.37	5	5
PDGFB-D/PDGFRB/SHP2	0.023	0.068	-10000	0	-0.24	25	25
PDGFB-D/PDGFRB/GRB10	0.021	0.069	-10000	0	-0.24	26	26
cell cycle arrest	0.017	0.069	-10000	0	-0.24	26	26
HRAS	0.026	0.007	-10000	0	-10000	0	0
HIF1A	0.027	0.098	0.26	28	-10000	0	28
GAB1	0.038	0.099	0.28	11	-0.37	3	14
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	0.04	0.099	0.25	32	-0.32	2	34
PDGFB-D/PDGFRB	0.026	0.064	-10000	0	-0.2	25	25
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.024	0.067	-10000	0	-0.24	24	24
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.015	0.061	0.23	1	-10000	0	1
positive regulation of MAPKKK cascade	0.023	0.068	-10000	0	-0.24	25	25
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
mol:IP3	0.041	0.1	0.25	27	-0.39	5	32
E5	0	0.001	-10000	0	-10000	0	0
CSK	0.026	0.008	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7	0.014	0.074	-10000	0	-0.24	30	30
SHB	0.026	0.007	-10000	0	-10000	0	0
BLK	-0.05	0.17	0.35	2	-0.47	51	53
PTPN2	0.028	0.008	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.023	0.068	-10000	0	-0.24	25	25
BCAR1	0.027	0.006	-10000	0	-10000	0	0
VAV2	0.044	0.11	0.27	24	-0.4	3	27
CBL	0.027	0.006	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.022	0.07	-10000	0	-0.24	26	26
LCK	0.011	0.097	0.35	2	-0.41	9	11
PDGFRB	0.006	0.091	-10000	0	-0.35	25	25
ACP1	0.028	0.004	-10000	0	-10000	0	0
HCK	0.019	0.063	0.36	3	-10000	0	3
ABL1	0.036	0.1	0.24	29	-0.36	5	34
PDGFB-D/PDGFRB/CBL	0.034	0.1	0.29	7	-0.42	5	12
PTPN1	0.022	0.012	-10000	0	-10000	0	0
SNX15	0.027	0.005	-10000	0	-10000	0	0
STAT3	0.028	0.004	-10000	0	-10000	0	0
STAT1	0.018	0.059	-10000	0	-0.35	10	10
cell proliferation	0.081	0.14	0.38	37	-0.66	2	39
SLA	0.022	0.028	-10000	0	-0.35	2	2
actin cytoskeleton reorganization	0.05	0.095	0.34	13	-10000	0	13
SRC	0.014	0.062	0.35	2	-0.34	1	3
PI3K	-0.005	0.041	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	0.028	0.069	-10000	0	-0.2	30	30
SH2B2	0.024	0.027	-10000	0	-0.35	2	2
PLCgamma1/SPHK1	0.048	0.11	0.26	27	-0.38	3	30
LYN	0.013	0.089	0.35	3	-0.42	7	10
LRP1	0.027	0.005	-10000	0	-10000	0	0
SOS1	0.028	0.003	-10000	0	-10000	0	0
STAT5B	0.027	0.005	-10000	0	-10000	0	0
STAT5A	0.028	0.004	-10000	0	-10000	0	0
NCK1-2/p130 Cas	0.045	0.067	-10000	0	-10000	0	0
SPHK1	0.013	0.078	-10000	0	-0.35	18	18
EDG1	0.001	0.003	-10000	0	-10000	0	0
mol:DAG	0.041	0.1	0.25	27	-0.39	5	32
PLCG1	0.041	0.1	0.26	26	-0.4	5	31
NHERF/PDGFRB	0.037	0.063	-10000	0	-0.2	25	25
YES1	0.015	0.093	0.36	1	-0.59	5	6
cell migration	0.036	0.063	-10000	0	-0.2	25	25
SHC/Grb2/SOS1	0.045	0.067	-10000	0	-10000	0	0
SLC9A3R2	0.027	0.006	-10000	0	-10000	0	0
SLC9A3R1	0.028	0.004	-10000	0	-10000	0	0
NHERF1-2/PDGFRB/PTEN	0.047	0.064	-10000	0	-10000	0	0
FYN	0.008	0.095	0.35	3	-0.38	11	14
DOK1	0.031	0.084	0.18	76	-10000	0	76
HRAS/GTP	0.02	0.005	-10000	0	-10000	0	0
PDGFB	0.024	0.033	-10000	0	-0.35	3	3
RAC1	0.054	0.12	0.36	21	-0.39	4	25
PRKCD	0.032	0.085	0.18	76	-10000	0	76
FER	0.027	0.081	0.18	63	-10000	0	63
MAPKKK cascade	0.016	0.092	0.29	12	-10000	0	12
RASA1	0.028	0.082	0.18	65	-10000	0	65
NCK1	0.027	0.005	-10000	0	-10000	0	0
NCK2	0.028	0.004	-10000	0	-10000	0	0
p62DOK/Csk	0.042	0.078	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SHB	0.022	0.068	-10000	0	-0.24	25	25
chemotaxis	0.036	0.1	0.24	30	-0.35	5	35
STAT1-3-5/STAT1-3-5	0.031	0.068	-10000	0	-0.32	1	1
Bovine Papilomavirus E5/PDGFRB	0.005	0.063	-10000	0	-0.24	25	25
PTPRJ	0.027	0.019	-10000	0	-0.35	1	1

×

Regulation of Androgen receptor activity

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
HDAC1	0.011	0.007	-10000	0	-10000	0	0
SMARCC1	0.013	0.011	-10000	0	-10000	0	0
REL	0.028	0.004	-10000	0	-10000	0	0
HDAC7	-0.017	0.089	0.22	2	-0.39	3	5
JUN	0.027	0.004	-10000	0	-10000	0	0
EP300	0.027	0.005	-10000	0	-10000	0	0
KAT2B	0.024	0.041	-10000	0	-0.38	4	4
KAT5	0.027	0.005	-10000	0	-10000	0	0
MAPK14	0.002	0.039	-10000	0	-0.28	6	6
FOXO1	0.026	0.008	-10000	0	-10000	0	0
T-DHT/AR	0.003	0.1	0.25	1	-0.41	3	4
MAP2K6	0.015	0.053	-10000	0	-0.39	6	6
BRM/BAF57	0.032	0.023	-10000	0	-0.27	1	1
MAP2K4	0.019	0.019	-10000	0	-10000	0	0
SMARCA2	0.023	0.023	-10000	0	-0.38	1	1
PDE9A	-0.11	0.33	-10000	0	-0.92	52	52
NCOA2	0.024	0.022	-10000	0	-0.38	1	1
CEBPA	0.021	0.044	-10000	0	-0.37	5	5
EHMT2	0.026	0.007	-10000	0	-10000	0	0
cell proliferation	0.009	0.13	0.28	23	-0.4	8	31
NR0B1	0.018	0.037	-10000	0	-0.35	4	4
EGR1	0.017	0.064	-10000	0	-0.38	10	10
RXRs/9cRA	-0.052	0.12	-10000	0	-0.21	159	159
AR/RACK1/Src	0.013	0.086	0.2	23	-0.3	2	25
AR/GR	-0.014	0.094	0.2	1	-0.26	30	31
GNB2L1	0.027	0.006	-10000	0	-10000	0	0
PKN1	0.027	0.005	-10000	0	-10000	0	0
RCHY1	0.027	0.005	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0.002	-10000	0	-0.015	2	2
MAPK8	0.006	0.018	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	0.007	0.071	0.24	2	-0.28	1	3
SRC	-0.01	0.049	0.19	14	-0.26	3	17
NR3C1	0.022	0.045	-10000	0	-0.38	5	5
KLK3	-0.1	0.12	-10000	0	-0.48	8	8
APPBP2	0.022	0.019	-10000	0	-10000	0	0
TRIM24	0.026	0.02	-10000	0	-0.35	1	1
T-DHT/AR/TIP60	-0.004	0.065	0.2	4	-0.32	2	6
TMPRSS2	-0.06	0.23	-10000	0	-0.83	27	27
RXRG	-0.14	0.2	-10000	0	-0.38	165	165
mol:9cRA	0	0.001	-10000	0	-10000	0	0
RXRA	0.026	0.021	-10000	0	-0.39	1	1
RXRB	0.027	0.006	-10000	0	-10000	0	0
CARM1	0.027	0.006	-10000	0	-10000	0	0
NR2C2	0.028	0.004	-10000	0	-10000	0	0
KLK2	-0.003	0.087	0.33	1	-0.32	5	6
AR	-0.021	0.085	0.17	2	-0.25	45	47
SENP1	0.027	0.005	-10000	0	-10000	0	0
HSP90AA1	0.025	0.027	-10000	0	-0.35	2	2
MDM2	0.025	0.028	-10000	0	-0.35	2	2
SRY	0	0.004	0.014	24	-10000	0	24
GATA2	0.022	0.045	-10000	0	-0.38	5	5
MYST2	0	0	-10000	0	-10000	0	0
HOXB13	-0.22	0.18	-10000	0	-0.36	270	270
T-DHT/AR/RACK1/Src	0.017	0.09	0.21	35	-0.31	2	37
positive regulation of transcription	0.022	0.045	-10000	0	-0.38	5	5
DNAJA1	0.02	0.019	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.017	0.011	-10000	0	-10000	0	0
NCOA1	0.032	0.013	-10000	0	-10000	0	0
SPDEF	-0.054	0.16	-10000	0	-0.38	79	79
T-DHT/AR/TIF2	0.003	0.072	0.22	4	-0.35	4	8
T-DHT/AR/Hsp90	-0.006	0.066	0.2	4	-0.32	2	6
GSK3B	0.027	0.005	-10000	0	-10000	0	0
NR2C1	0.028	0.004	-10000	0	-10000	0	0
mol:T-DHT	-0.017	0.038	0.25	1	-0.25	5	6
SIRT1	0.027	0.005	-10000	0	-10000	0	0
ZMIZ2	0.027	0.008	-10000	0	-10000	0	0
POU2F1	0.016	0.05	-10000	0	-0.35	1	1
T-DHT/AR/DAX-1	-0.01	0.069	0.22	3	-0.29	4	7
CREBBP	0.026	0.007	-10000	0	-10000	0	0
SMARCE1	0.026	0.008	-10000	0	-10000	0	0

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.02	0.003	-10000	0	-10000	0	0
PRKCZ	0.026	0.007	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.026	0.007	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	0.006	0.056	-10000	0	-0.42	2	2
IRAK/TOLLIP	0.03	0.009	-10000	0	-10000	0	0
IKBKB	0.025	0.009	-10000	0	-10000	0	0
IKBKG	0.027	0.006	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.054	0.14	-10000	0	-0.26	129	129
IL1A	-0.039	0.14	-10000	0	-0.35	72	72
IL1B	-0.017	0.085	-10000	0	-0.26	45	45
IRAK/TRAF6/p62/Atypical PKCs	0.055	0.034	-10000	0	-10000	0	0
IL1R2	-0.033	0.15	-10000	0	-0.38	61	61
IL1R1	0.027	0.019	-10000	0	-0.35	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.003	0.064	0.24	1	-0.42	3	4
TOLLIP	0.027	0.006	-10000	0	-10000	0	0
TICAM2	0.022	0.041	-10000	0	-0.38	4	4
MAP3K3	0.027	0.005	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.018	0.004	-10000	0	-10000	0	0
IKK complex/ELKS	0.022	0.067	-10000	0	-0.34	2	2
JUN	-0.009	0.032	0.16	10	-10000	0	10
MAP3K7	0.027	0.006	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.03	0.084	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88	0.018	0.1	-10000	0	-0.2	70	70
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.027	0.1	-10000	0	-0.34	3	3
IL1 beta fragment/IL1R1/IL1RAP	0.011	0.08	-10000	0	-0.19	53	53
NFKB1	0.027	0.005	-10000	0	-10000	0	0
MAPK8	-0.007	0.034	0.17	10	-10000	0	10
IRAK1	0.014	0.003	-10000	0	-10000	0	0
IL1RN/IL1R1	0.01	0.093	-10000	0	-0.27	42	42
IRAK4	0.027	0.005	-10000	0	-10000	0	0
PRKCI	0.024	0.027	-10000	0	-0.35	2	2
TRAF6	0.027	0.005	-10000	0	-10000	0	0
PI3K	0.036	0.014	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.01	0.054	-10000	0	-0.36	1	1
CHUK	0.027	0.006	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.011	0.08	-10000	0	-0.19	53	53
IL1 beta/IL1R2	-0.03	0.12	-10000	0	-0.23	100	100
IRAK/TRAF6/TAK1/TAB1/TAB2	0.036	0.013	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.02	0.075	-10000	0	-10000	0	0
IRAK3	0.02	0.053	-10000	0	-0.38	7	7
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.028	0.087	-10000	0	-0.33	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.004	0.053	-10000	0	-0.27	2	2
IL1 alpha/IL1R1/IL1RAP	0.005	0.1	-10000	0	-0.22	72	72
RELA	0.027	0.005	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.027	0.006	-10000	0	-10000	0	0
MYD88	0.027	0.005	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0.044	0.016	-10000	0	-10000	0	0
IL1RAP	0.019	0.053	-10000	0	-0.35	8	8
UBE2N	0.028	0.004	-10000	0	-10000	0	0
IRAK/TRAF6	0.006	0.068	-10000	0	-0.3	1	1
CASP1	0.021	0.049	-10000	0	-0.35	7	7
IL1RN/IL1R2	-0.032	0.15	-10000	0	-0.32	84	84
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.023	0.082	-10000	0	-10000	0	0
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.011	0.059	-10000	0	-0.28	4	4
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
IL1RN	-0.013	0.12	-10000	0	-0.38	41	41
TRAF6/TAK1/TAB1/TAB2	0.038	0.011	-10000	0	-10000	0	0
MAP2K6	0.014	0.034	0.18	10	-10000	0	10

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.026	0.007	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	0.017	0.093	-9999	-0.34	9	9
Syndecan-3/Neurocan	0.012	0.078	-9999	-0.37	13	13
POMC	0.001	0.1	-9999	-0.38	27	27
EGFR	0.017	0.057	-9999	-0.38	8	8
Syndecan-3/EGFR	0.015	0.071	-9999	-0.37	10	10
AGRP	0.015	0.058	-9999	-0.35	10	10
NCSTN	0.027	0.005	-9999	-10000	0	0
PSENEN	0.027	0.007	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.027	0.005	-9999	-10000	0	0
APH1A	0.027	0.006	-9999	-10000	0	0
NCAN	0.011	0.071	-9999	-0.35	15	15
long-term memory	0.034	0.069	-9999	-0.35	11	11
Syndecan-3/IL8	-0.067	0.12	-9999	-0.48	13	13
PSEN1	0.027	0.005	-9999	-10000	0	0
Src/Cortactin	0.034	0.017	-9999	-10000	0	0
FYN	0.027	0.005	-9999	-10000	0	0
limb bud formation	0.001	0.069	-9999	-0.38	13	13
MC4R	0.021	0.009	-9999	-10000	0	0
SRC	0.024	0.01	-9999	-10000	0	0
PTN	-0.032	0.14	-9999	-0.38	59	59
FGFR/FGF/Syndecan-3	0.001	0.069	-9999	-0.38	13	13
neuron projection morphogenesis	0.005	0.098	-9999	-0.33	10	10
Syndecan-3/AgRP	0.013	0.075	-9999	-0.36	13	13
Syndecan-3/AgRP/MC4R	0.023	0.076	-9999	-0.34	13	13
Fyn/Cortactin	0.038	0.012	-9999	-10000	0	0
SDC3	0.001	0.07	-9999	-0.38	13	13
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.067	0.12	-9999	-0.48	13	13
IL8	-0.16	0.19	-9999	-0.35	198	198
Syndecan-3/Fyn/Cortactin	0.035	0.07	-9999	-0.35	11	11
Syndecan-3/CASK	0	0.067	-9999	-0.36	13	13
alpha-MSH/MC4R	0.015	0.074	-9999	-0.26	26	26
Gamma Secretase	0.072	0.03	-9999	-10000	0	0

×

Syndecan-4-mediated 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
PTK2	0.002	0.072	-10000	0	-0.3	2	2
Syndecan-4/Syndesmos	-0.004	0.11	0.3	1	-0.44	1	2
positive regulation of JNK cascade	-0.013	0.13	0.29	2	-0.36	7	9
Syndecan-4/ADAM12	-0.09	0.15	0.3	1	-0.38	23	24
CCL5	0.019	0.059	-10000	0	-0.38	9	9
Rac1/GDP	0.019	0.006	-10000	0	-10000	0	0
DNM2	0.027	0.005	-10000	0	-10000	0	0
ITGA5	0.021	0.049	-10000	0	-0.35	7	7
SDCBP	0.025	0.009	-10000	0	-10000	0	0
PLG	0.004	0.047	-10000	0	-0.35	5	5
ADAM12	-0.19	0.19	-10000	0	-0.35	230	230
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0.027	0.006	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.041	0.034	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	-0.032	0.14	0.3	2	-0.37	15	17
Syndecan-4/CXCL12/CXCR4	-0.013	0.14	0.31	2	-0.39	6	8
Syndecan-4/Laminin alpha3	-0.008	0.12	0.31	1	-0.45	3	4
MDK	0.012	0.074	-10000	0	-0.36	16	16
Syndecan-4/FZD7	-0.002	0.12	0.3	2	-0.44	1	3
Syndecan-4/Midkine	-0.01	0.12	0.3	2	-0.44	3	5
FZD7	0.025	0.033	-10000	0	-0.36	3	3
Syndecan-4/FGFR1/FGF	-0.007	0.12	0.29	1	-0.4	4	5
THBS1	0.018	0.059	-10000	0	-0.36	10	10
integrin-mediated signaling pathway	-0.012	0.12	0.29	1	-0.36	6	7
positive regulation of MAPKKK cascade	-0.013	0.13	0.29	2	-0.36	7	9
Syndecan-4/TACI	-0.042	0.13	0.3	1	-0.39	14	15
CXCR4	0.005	0.091	-10000	0	-0.35	25	25
cell adhesion	0.002	0.05	0.19	6	-0.2	8	14
Syndecan-4/Dynamin	0	0.12	0.3	2	-0.44	1	3
Syndecan-4/TSP1	-0.006	0.12	0.3	2	-0.39	3	5
Syndecan-4/GIPC	0	0.12	0.3	2	-0.44	1	3
Syndecan-4/RANTES	-0.005	0.12	0.3	2	-0.44	1	3
ITGB1	0.026	0.02	-10000	0	-0.35	1	1
LAMA1	-0.044	0.15	-10000	0	-0.36	76	76
LAMA3	0.014	0.066	-10000	0	-0.36	12	12
RAC1	0.026	0.008	-10000	0	-10000	0	0
PRKCA	0.017	0.1	0.77	7	-10000	0	7
Syndecan-4/alpha-Actinin	-0.003	0.12	0.3	1	-0.44	1	2
TFPI	0.026	0.019	-10000	0	-0.35	1	1
F2	-0.031	0.13	-10000	0	-0.35	60	60
alpha5/beta1 Integrin	0.033	0.043	-10000	0	-0.28	7	7
positive regulation of cell adhesion	-0.039	0.13	0.28	2	-0.38	14	16
ACTN1	0.024	0.033	-10000	0	-0.35	3	3
TNC	0.001	0.096	-10000	0	-0.36	28	28
Syndecan-4/CXCL12	-0.012	0.12	0.3	2	-0.41	4	6
FGF6	0.017	0.026	-10000	0	-0.35	2	2
RHOA	0.027	0.006	-10000	0	-10000	0	0
CXCL12	0.001	0.1	-10000	0	-0.38	26	26
TNFRSF13B	-0.069	0.17	-10000	0	-0.38	94	94
FGF2	0.009	0.084	-10000	0	-0.38	18	18
FGFR1	0.022	0.035	-10000	0	-0.38	3	3
Syndecan-4/PI-4-5-P2	-0.036	0.082	-10000	0	-0.44	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	-0.02	0.11	-10000	0	-0.35	41	41
cell migration	-0.019	0.014	-10000	0	-10000	0	0
PRKCD	0.017	0.025	-10000	0	-10000	0	0
vasculogenesis	-0.005	0.12	0.3	2	-0.38	3	5
SDC4	-0.034	0.085	-10000	0	-0.46	1	1
Syndecan-4/Tenascin C	-0.012	0.13	0.3	1	-0.38	6	7
Syndecan-4/PI-4-5-P2/PKC alpha	-0.033	0.027	-10000	0	-10000	0	0
Syndecan-4/Syntenin	-0.004	0.11	0.3	2	-0.42	1	3
MMP9	-0.063	0.16	-10000	0	-0.35	92	92
Rac1/GTP	0.002	0.051	0.19	6	-0.2	8	14
cytoskeleton organization	-0.004	0.11	0.29	1	-0.43	1	2
GIPC1	0.027	0.005	-10000	0	-10000	0	0
Syndecan-4/TFPI	-0.003	0.12	0.3	1	-0.44	1	2

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.011	0.05	-9999	-0.26	7	7
STMN1	0.009	0.036	-9999	-0.24	8	8
Aurora B/RasGAP/Survivin	0.037	0.073	-9999	-0.24	20	20
Chromosomal passenger complex/Cul3 protein complex	-0.017	0.089	-9999	-0.31	18	18
BIRC5	0.01	0.084	-9999	-0.36	20	20
DES	-0.3	0.32	-9999	-0.59	217	217
Aurora C/Aurora B/INCENP	0.04	0.06	-9999	-0.21	20	20
Aurora B/TACC1	0.031	0.034	-9999	-0.2	7	7
Aurora B/PP2A	0.035	0.042	-9999	-0.24	8	8
mol:GTP	0	0	-9999	-10000	0	0
CBX5	0.008	0.012	-9999	-0.14	1	1
mitotic metaphase/anaphase transition	0.001	0.004	-9999	-10000	0	0
NDC80	0	0.064	-9999	-0.28	20	20
Cul3 protein complex	0.017	0.089	-9999	-0.23	46	46
KIF2C	0.004	0.067	-9999	-0.34	9	9
PEBP1	0.027	0.006	-9999	-10000	0	0
KIF20A	0.004	0.091	-9999	-0.35	25	25
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	0.033	0.044	-9999	-0.24	9	9
SEPT1	0.023	0.038	-9999	-0.36	4	4
SMC2	0.027	0.005	-9999	-10000	0	0
SMC4	0.027	0.006	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.026	0.16	-9999	-0.54	31	31
PSMA3	0.027	0.005	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.003	-9999	-10000	0	0
H3F3B	0.012	0.026	-9999	-0.28	1	1
AURKB	0.023	0.058	-9999	-0.36	9	9
AURKC	0.014	0.068	-9999	-0.36	13	13
CDCA8	0.027	0.021	-9999	-0.37	1	1
cytokinesis	-0.025	0.1	-9999	-0.44	13	13
Aurora B/Septin1	-0.002	0.12	-9999	-0.4	14	14
AURKA	0.011	0.064	-9999	-0.36	12	12
INCENP	0.028	0.008	-9999	-10000	0	0
KLHL13	-0.021	0.13	-9999	-0.38	49	49
BUB1	-0.024	0.13	-9999	-0.35	57	57
hSgo1/Aurora B/Survivin	0.029	0.087	-9999	-0.23	37	37
EVI5	0.028	0.005	-9999	-10000	0	0
RhoA/GTP	0.014	0.11	-9999	-0.37	11	11
SGOL1	0.011	0.078	-9999	-0.35	18	18
CENPA	0.01	0.079	-9999	-0.31	13	13
NCAPG	0.021	0.046	-9999	-0.35	6	6
Aurora B/HC8 Proteasome	0.036	0.044	-9999	-0.24	9	9
NCAPD2	0.027	0.006	-9999	-10000	0	0
Aurora B/PP1-gamma	0.036	0.044	-9999	-0.24	9	9
RHOA	0.027	0.006	-9999	-10000	0	0
NCAPH	0.026	0.027	-9999	-0.35	2	2
NPM1	-0.02	0.12	-9999	-0.39	29	29
RASA1	0.025	0.008	-9999	-10000	0	0
KLHL9	0.024	0.01	-9999	-10000	0	0
mitotic prometaphase	0	0.003	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.036	0.044	-9999	-0.24	9	9
PPP1CC	0.028	0.004	-9999	-10000	0	0
Centraspindlin	0.007	0.11	-9999	-0.35	17	17
RhoA/GDP	0.02	0.004	-9999	-10000	0	0
NSUN2	-0.01	0.096	-9999	-0.33	27	27
MYLK	-0.002	0.058	-9999	-0.26	13	13
KIF23	-0.02	0.13	-9999	-0.35	52	52
VIM	0.009	0.038	-9999	-0.24	9	9
RACGAP1	0.028	0.006	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
NCL	-0.012	0.099	-9999	-0.33	29	29
Chromosomal passenger complex	-0.001	0.081	-9999	-0.34	13	13
Chromosomal passenger complex/EVI5	0.08	0.087	-9999	-0.34	5	5
TACC1	0.025	0.009	-9999	-10000	0	0
PPP2R5D	0.026	0.007	-9999	-10000	0	0
CUL3	0.028	0.004	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	-0.004	0.01	-10000	0	-10000	0	0
RAS family/GTP	-0.015	0.094	0.23	1	-0.54	1	2
NFATC4	-0.019	0.093	0.28	13	-0.38	1	14
ERBB2IP	0.026	0.009	-10000	0	-10000	0	0
HSP90 (dimer)	0.025	0.027	-10000	0	-0.35	2	2
mammary gland morphogenesis	-0.032	0.087	-10000	0	-0.29	4	4
JUN	-0.009	0.07	0.18	9	-0.23	7	16
HRAS	0.026	0.007	-10000	0	-10000	0	0
DOCK7	-0.034	0.092	0.26	3	-0.47	1	4
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.002	0.1	-10000	0	-0.22	66	66
AKT1	0.004	0.008	-10000	0	-10000	0	0
BAD	-0.005	0.007	-10000	0	-10000	0	0
MAPK10	-0.02	0.08	0.19	17	-0.23	11	28
mol:GTP	-0.001	0.001	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.034	0.093	-10000	0	-0.31	4	4
RAF1	-0.024	0.099	0.26	6	-0.55	1	7
ErbB2/ErbB3/neuregulin 2	-0.043	0.11	-10000	0	-0.22	103	103
STAT3	0.024	0.056	-10000	0	-0.74	2	2
cell migration	-0.012	0.088	0.24	20	-0.22	9	29
mol:PI-3-4-5-P3	-0.001	0.002	-10000	0	-10000	0	0
cell proliferation	-0.08	0.17	-10000	0	-0.58	9	9
FOS	-0.058	0.14	0.31	3	-0.44	27	30
NRAS	0.027	0.005	-10000	0	-10000	0	0
mol:Ca2+	-0.032	0.087	-10000	0	-0.29	4	4
MAPK3	-0.063	0.15	0.3	2	-0.52	9	11
MAPK1	-0.069	0.16	0.31	2	-0.58	11	13
JAK2	-0.035	0.086	0.26	1	-0.47	1	2
NF2	-0.006	0.091	-10000	0	-0.65	8	8
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.019	0.097	0.18	8	-0.22	61	69
NRG1	-0.056	0.16	-10000	0	-0.38	81	81
GRB2/SOS1	0.04	0.008	-10000	0	-10000	0	0
MAPK8	-0.03	0.1	0.21	4	-0.24	55	59
MAPK9	-0.007	0.074	0.19	24	-0.24	1	25
ERBB2	-0.02	0.025	-10000	0	-0.29	3	3
ERBB3	0.024	0.03	-10000	0	-0.39	2	2
SHC1	0.027	0.005	-10000	0	-10000	0	0
RAC1	0.026	0.008	-10000	0	-10000	0	0
apoptosis	0.008	0.011	-10000	0	-10000	0	0
STAT3 (dimer)	0.024	0.055	-10000	0	-0.73	2	2
RNF41	-0.007	0.011	-10000	0	-10000	0	0
FRAP1	-0.002	0.005	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.03	0.059	-10000	0	-0.34	1	1
ErbB2/ErbB2/HSP90 (dimer)	-0.006	0.03	-10000	0	-0.24	4	4
CHRNA1	-0.081	0.15	0.28	2	-0.43	10	12
myelination	-0.007	0.11	0.28	28	-0.37	1	29
PPP3CB	-0.033	0.082	0.25	1	-0.44	1	2
KRAS	0.024	0.009	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0.005	0.098	-10000	0	-0.38	2	2
NRG2	-0.099	0.19	-10000	0	-0.38	125	125
mol:GDP	-0.019	0.096	0.18	8	-0.22	61	69
SOS1	0.027	0.003	-10000	0	-10000	0	0
MAP2K2	-0.035	0.098	0.26	5	-0.54	1	6
SRC	0.024	0.01	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.001	-10000	0	-10000	0	0
PTPN11	-0.034	0.091	0.26	3	-0.47	1	4
MAP2K1	-0.063	0.16	-10000	0	-0.57	10	10
heart morphogenesis	-0.032	0.087	-10000	0	-0.29	4	4
RAS family/GDP	0.009	0.098	0.25	1	-0.53	1	2
GRB2	0.027	0.005	-10000	0	-10000	0	0
PRKACA	-0.008	0.11	-10000	0	-0.66	11	11
CHRNE	0.001	0.026	0.08	2	-0.14	9	11
HSP90AA1	0.025	0.027	-10000	0	-0.35	2	2
activation of caspase activity	-0.004	0.008	-10000	0	-10000	0	0
nervous system development	-0.032	0.087	-10000	0	-0.29	4	4
CDC42	0.026	0.007	-10000	0	-10000	0	0

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.023	0.015	-9999	-10000	0	0
SVIL	0.022	0.03	-9999	-0.35	2	2
ZNF318	0.028	0.014	-9999	-10000	0	0
JMJD2C	-0.002	0.019	-9999	-0.073	26	26
T-DHT/AR/Ubc9	-0.002	0.091	-9999	-0.22	53	53
CARM1	0.027	0.005	-9999	-10000	0	0
PRDX1	0.028	0.004	-9999	-10000	0	0
PELP1	0.026	0.008	-9999	-10000	0	0
CTNNB1	0.024	0.014	-9999	-10000	0	0
AKT1	0.027	0.007	-9999	-10000	0	0
PTK2B	0.022	0.015	-9999	-10000	0	0
MED1	0.027	0.008	-9999	-10000	0	0
MAK	0.017	0.068	-9999	-0.35	13	13
response to oxidative stress	0	0.001	-9999	-10000	0	0
HIP1	0.024	0.014	-9999	-10000	0	0
GSN	0.017	0.055	-9999	-0.38	7	7
NCOA2	0.024	0.022	-9999	-0.38	1	1
NCOA6	0.022	0.015	-9999	-10000	0	0
DNA-PK	0.05	0.025	-9999	-10000	0	0
NCOA4	0.027	0.006	-9999	-10000	0	0
PIAS3	0.024	0.013	-9999	-10000	0	0
cell proliferation	-0.006	0.084	-9999	-0.44	11	11
XRCC5	0.028	0.005	-9999	-10000	0	0
UBE3A	0.024	0.017	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.046	0.13	-9999	-0.25	113	113
FHL2	0.005	0.1	-9999	-0.71	6	6
RANBP9	0.024	0.015	-9999	-10000	0	0
JMJD1A	-0.001	0.025	-9999	-0.13	15	15
CDK6	0.021	0.038	-9999	-0.35	4	4
TGFB1I1	0.02	0.04	-9999	-0.36	4	4
T-DHT/AR/CyclinD1	-0.002	0.09	-9999	-0.22	52	52
XRCC6	0.027	0.006	-9999	-10000	0	0
T-DHT/AR	0.002	0.1	-9999	-0.23	51	51
CTDSP1	0.027	0.004	-9999	-10000	0	0
CTDSP2	0.028	0.01	-9999	-10000	0	0
BRCA1	0.024	0.023	-9999	-0.35	1	1
TCF4	0.025	0.011	-9999	-10000	0	0
CDKN2A	-0.087	0.17	-9999	-0.35	121	121
SRF	0.029	0.019	-9999	-10000	0	0
NKX3-1	-0.015	0.055	-9999	-0.21	19	19
KLK3	-0.005	0.081	-9999	-10000	0	0
TMF1	0.027	0.005	-9999	-10000	0	0
HNRNPA1	0.028	0.007	-9999	-10000	0	0
AOF2	-0.001	0.005	-9999	-10000	0	0
APPL1	0.014	0.008	-9999	-10000	0	0
T-DHT/AR/Caspase 8	0.001	0.091	-9999	-0.23	50	50
AR	-0.028	0.14	-9999	-0.38	51	51
UBA3	0.027	0.005	-9999	-10000	0	0
PATZ1	0.028	0.007	-9999	-10000	0	0
PAWR	0.027	0.005	-9999	-10000	0	0
PRKDC	0.025	0.01	-9999	-10000	0	0
PA2G4	0.028	0.008	-9999	-10000	0	0
UBE2I	0.026	0.007	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	0.001	0.081	-9999	-0.2	48	48
RPS6KA3	0.024	0.015	-9999	-10000	0	0
T-DHT/AR/ARA70	-0.001	0.091	-9999	-0.22	53	53
LATS2	0.027	0.008	-9999	-10000	0	0
T-DHT/AR/PRX1	0.003	0.083	-9999	-0.2	50	50
Cyclin D3/CDK11 p58	0.019	0.006	-9999	-10000	0	0
VAV3	-0.001	0.096	-9999	-0.36	28	28
KLK2	-0.02	0.09	-9999	-0.31	29	29
CASP8	0.028	0.004	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	0.011	0.087	-9999	-0.21	46	46
TMPRSS2	-0.031	0.17	-9999	-0.73	20	20
CCND1	0.025	0.02	-9999	-0.35	1	1
PIAS1	0.024	0.016	-9999	-10000	0	0
mol:T-DHT	-0.002	0.017	-9999	-0.07	17	17
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.022	0.021	-9999	-10000	0	0
T-DHT/AR/CDK6	0	0.088	-9999	-0.23	47	47
CMTM2	0.015	0.065	-9999	-0.36	12	12
SNURF	-0.048	0.16	-9999	-0.38	72	72
ZMIZ1	0.021	0.027	-9999	-10000	0	0
CCND3	0.026	0.008	-9999	-10000	0	0
TGIF1	0.027	0.008	-9999	-10000	0	0
FKBP4	0.024	0.014	-9999	-10000	0	0

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.014	0.11	-10000	0	-0.39	14	14
TBX21	-0.088	0.26	0.52	1	-0.91	20	21
B2M	0.016	0.023	-10000	0	-10000	0	0
TYK2	0.015	0.031	-10000	0	-10000	0	0
IL12RB1	0.011	0.052	-10000	0	-0.41	4	4
GADD45B	-0.07	0.24	-10000	0	-0.78	20	20
IL12RB2	0.004	0.078	-10000	0	-0.38	14	14
GADD45G	-0.065	0.23	-10000	0	-0.78	17	17
natural killer cell activation	-0.002	0.017	0.044	1	-0.041	20	21
RELB	0.026	0.02	-10000	0	-0.35	1	1
RELA	0.027	0.005	-10000	0	-10000	0	0
IL18	0.016	0.042	-10000	0	-0.36	4	4
IL2RA	-0.004	0.1	-10000	0	-0.35	33	33
IFNG	-0.067	0.16	-10000	0	-0.35	101	101
STAT3 (dimer)	-0.068	0.22	-10000	0	-0.66	25	25
HLA-DRB5	0	0.005	-10000	0	-0.025	11	11
FASLG	-0.095	0.29	-10000	0	-1	23	23
NF kappa B2 p52/RelB	-0.078	0.25	-10000	0	-0.74	27	27
CD4	0.022	0.03	-10000	0	-0.35	2	2
SOCS1	0.021	0.047	-10000	0	-0.36	6	6
EntrezGene:6955	-0.004	0.011	-10000	0	-0.03	22	22
CD3D	0.009	0.051	-10000	0	-0.39	5	5
CD3E	0.011	0.046	-10000	0	-0.38	4	4
CD3G	0.006	0.061	-10000	0	-0.39	8	8
IL12Rbeta2/JAK2	0.017	0.064	-10000	0	-0.27	11	11
CCL3	-0.11	0.28	-10000	0	-0.84	25	25
CCL4	-0.089	0.27	-10000	0	-0.87	25	25
HLA-A	-0.004	0.009	-10000	0	-0.026	13	13
IL18/IL18R	0.021	0.077	-10000	0	-0.25	13	13
NOS2	-0.13	0.28	-10000	0	-0.85	30	30
IL12/IL12R/TYK2/JAK2/SPHK2	-0.012	0.11	-10000	0	-0.36	17	17
IL1R1	-0.082	0.25	0.51	1	-0.85	18	19
IL4	0.002	0.056	-10000	0	-0.35	7	7
JAK2	0.014	0.029	-10000	0	-10000	0	0
EntrezGene:6957	-0.004	0.01	-10000	0	-0.031	14	14
TCR/CD3/MHC I/CD8	-0.045	0.16	-10000	0	-0.64	16	16
RAB7A	-0.053	0.21	-10000	0	-0.73	11	11
lysosomal transport	-0.05	0.2	-10000	0	-0.69	11	11
FOS	-0.085	0.31	-10000	0	-1	33	33
STAT4 (dimer)	-0.056	0.24	0.38	3	-0.78	19	22
STAT5A (dimer)	-0.12	0.26	-10000	0	-0.77	29	29
GZMA	-0.1	0.3	-10000	0	-1	26	26
GZMB	-0.095	0.27	-10000	0	-0.92	22	22
HLX	0.026	0.019	-10000	0	-0.35	1	1
LCK	-0.096	0.26	-10000	0	-0.81	26	26
TCR/CD3/MHC II/CD4	-0.007	0.087	-10000	0	-0.4	12	12
IL2/IL2R	0.034	0.082	-10000	0	-0.26	6	6
MAPK14	-0.068	0.24	-10000	0	-0.81	17	17
CCR5	-0.067	0.23	-10000	0	-0.81	15	15
IL1B	-0.022	0.12	-10000	0	-0.38	41	41
STAT6	-0.014	0.1	-10000	0	-0.9	2	2
STAT4	0.024	0.038	-10000	0	-0.35	4	4
STAT3	0.028	0.004	-10000	0	-10000	0	0
STAT1	0.018	0.059	-10000	0	-0.35	10	10
NFKB1	0.027	0.005	-10000	0	-10000	0	0
NFKB2	0.027	0.006	-10000	0	-10000	0	0
IL12B	0.009	0.051	-10000	0	-0.35	5	5
CD8A	0.005	0.071	-10000	0	-0.38	12	12
CD8B	-0.012	0.1	-10000	0	-0.38	30	30
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.014	0.11	0.39	14	-10000	0	14
IL2RB	0.026	0.021	-10000	0	-0.38	1	1
proteasomal ubiquitin-dependent protein catabolic process	-0.05	0.22	0.38	3	-0.71	19	22
IL2RG	0.019	0.059	-10000	0	-0.38	9	9
IL12	0.003	0.083	-10000	0	-0.27	26	26
STAT5A	0.028	0.004	-10000	0	-10000	0	0
CD247	0.009	0.055	-10000	0	-0.39	6	6
IL2	0.021	0.027	-10000	0	-0.35	2	2
SPHK2	0.027	0.006	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.006	0.095	-10000	0	-0.4	21	21
IL12/IL12R/TYK2/JAK2	-0.097	0.27	-10000	0	-0.82	29	29
MAP2K3	-0.077	0.25	-10000	0	-0.77	24	24
RIPK2	0.024	0.01	-10000	0	-10000	0	0
MAP2K6	-0.066	0.24	-10000	0	-0.76	21	21
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.001	0.006	-10000	0	-0.026	18	18
IL18RAP	0.008	0.07	-10000	0	-0.38	12	12
IL12Rbeta1/TYK2	0.021	0.053	-10000	0	-0.3	4	4
EOMES	-0.038	0.15	-10000	0	-1	4	4
STAT1 (dimer)	-0.088	0.22	-10000	0	-0.68	24	24
T cell proliferation	-0.041	0.19	0.41	2	-0.55	20	22
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.018	0.033	-10000	0	-0.38	2	2
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.057	0.2	-10000	0	-0.62	19	19
ATF2	-0.063	0.23	0.51	1	-0.75	17	18

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.02	0.076	0.38	14	-10000	0	14
VDR	0.027	0.005	-10000	0	-10000	0	0
FAM120B	0.026	0.007	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.055	0.12	-10000	0	-0.31	17	17
RXRs/LXRs/DNA/Oxysterols	-0.044	0.11	-10000	0	-0.37	7	7
MED1	0.026	0.008	-10000	0	-10000	0	0
mol:9cRA	0.002	0.007	-10000	0	-10000	0	0
RARs/THRs/DNA/Src-1	0.01	0.061	-10000	0	-0.29	2	2
RXRs/NUR77	-0.045	0.14	-10000	0	-0.31	15	15
RXRs/PPAR	-0.061	0.12	-10000	0	-0.32	19	19
NCOR2	0.027	0.005	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.02	0.004	-10000	0	-10000	0	0
RARs/VDR/DNA/Vit D3	0.056	0.032	-10000	0	-0.2	2	2
RARA	0.026	0.008	-10000	0	-10000	0	0
NCOA1	0.028	0.003	-10000	0	-10000	0	0
VDR/VDR/DNA	0.027	0.005	-10000	0	-10000	0	0
RARs/RARs/DNA/9cRA	0.042	0.027	-10000	0	-0.19	3	3
RARG	0.026	0.02	-10000	0	-0.35	1	1
RPS6KB1	0.032	0.072	0.59	6	-10000	0	6
RARs/THRs/DNA/SMRT	0.009	0.062	-10000	0	-0.33	2	2
THRA	0.025	0.009	-10000	0	-10000	0	0
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.02	0.004	-10000	0	-10000	0	0
RXRs/PPAR/9cRA/PGJ2/DNA	-0.047	0.12	-10000	0	-0.26	9	9
NR1H4	-0.055	0.16	-10000	0	-0.37	85	85
RXRs/LXRs/DNA	-0.026	0.14	-10000	0	-0.28	9	9
NR1H2	0.027	0.015	-10000	0	-10000	0	0
NR1H3	0.028	0.016	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.038	0.12	-10000	0	-0.23	9	9
NR4A1	0.016	0.067	-10000	0	-0.38	11	11
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.078	0.12	-10000	0	-0.29	45	45
RXRG	-0.14	0.2	-10000	0	-0.38	165	165
RXR alpha/CCPG	0.039	0.021	-10000	0	-0.27	1	1
RXRA	0.027	0.025	-10000	0	-0.38	1	1
RXRB	0.027	0.015	-10000	0	-10000	0	0
THRB	-0.002	0.11	-10000	0	-0.38	30	30
PPARG	0.022	0.045	-10000	0	-0.38	5	5
PPARD	0.027	0.005	-10000	0	-10000	0	0
TNF	-0.052	0.14	-10000	0	-0.9	5	5
mol:Oxysterols	0.002	0.007	-10000	0	-10000	0	0
cholesterol transport	-0.043	0.11	-10000	0	-0.37	7	7
PPARA	0.026	0.007	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.025	0.035	-10000	0	-0.38	3	3
RXRs/NUR77/BCL2	-0.075	0.13	-10000	0	-0.22	162	162
SREBF1	-0.039	0.1	-10000	0	-10000	0	0
RXRs/RXRs/DNA/9cRA	-0.047	0.13	-10000	0	-0.26	9	9
ABCA1	-0.041	0.1	-10000	0	-10000	0	0
RARs/THRs	0.05	0.077	-10000	0	-10000	0	0
RXRs/FXR	-0.086	0.15	-10000	0	-0.35	41	41
BCL2	0.024	0.022	-10000	0	-0.38	1	1

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.037	0.02	-10000	0	-0.24	1	1
PDGFRB	0.004	0.091	-10000	0	-0.35	25	25
SPHK1	-0.006	0.074	-10000	0	-0.61	5	5
mol:S1P	-0.01	0.067	-10000	0	-0.51	5	5
S1P1/S1P/Gi	-0.05	0.15	-10000	0	-0.41	36	36
GNAO1	-0.057	0.16	-10000	0	-0.39	82	82
PDGFB-D/PDGFRB/PLCgamma1	-0.029	0.15	0.27	14	-0.38	28	42
PLCG1	-0.052	0.13	0.27	2	-0.4	29	31
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.004	0.091	-10000	0	-0.35	25	25
GNAI2	0.026	0.01	-10000	0	-10000	0	0
GNAI3	0.027	0.006	-10000	0	-10000	0	0
GNAI1	0.019	0.054	-10000	0	-0.39	7	7
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	0.002	0.014	-10000	0	-0.2	1	1
S1P1/S1P	-0.001	0.059	-10000	0	-0.32	5	5
negative regulation of cAMP metabolic process	-0.049	0.14	-10000	0	-0.4	36	36
MAPK3	-0.055	0.15	0.31	2	-0.45	30	32
calcium-dependent phospholipase C activity	-0.001	0.002	-10000	0	-10000	0	0
Rac1/GDP	0.019	0.006	-10000	0	-10000	0	0
RhoA/GDP	0.02	0.004	-10000	0	-10000	0	0
KDR	0.028	0.005	-10000	0	-10000	0	0
PLCB2	0.011	0.076	0.22	13	-0.29	5	18
RAC1	0.026	0.008	-10000	0	-10000	0	0
RhoA/GTP	-0.001	0.051	-10000	0	-0.28	5	5
receptor internalization	-0.002	0.055	-10000	0	-0.3	5	5
PTGS2	-0.057	0.18	0.38	1	-0.65	14	15
Rac1/GTP	0	0.05	-10000	0	-0.28	5	5
RHOA	0.027	0.006	-10000	0	-10000	0	0
VEGFA	0.025	0.02	-10000	0	-0.35	1	1
negative regulation of T cell proliferation	-0.049	0.14	-10000	0	-0.4	36	36
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	0	0.1	-10000	0	-0.39	26	26
MAPK1	-0.053	0.15	-10000	0	-0.46	27	27
S1P1/S1P/PDGFB-D/PDGFRB	0.013	0.09	0.24	13	-0.33	2	15
ABCC1	0.027	0.006	-10000	0	-10000	0	0

×

Calcium signaling in the CD4+ TCR 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
NFATC1	-0.014	0.037	-10000	0	-0.22	2	2
NFATC2	-0.011	0.035	-10000	0	-0.22	3	3
NFATC3	-0.013	0.036	-10000	0	-10000	0	0
CD40LG	-0.079	0.19	0.35	1	-0.52	27	28
PTGS2	-0.088	0.2	0.35	1	-0.52	40	41
JUNB	0.027	0.005	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.005	0.028	-10000	0	-10000	0	0
CaM/Ca2+	-0.005	0.028	-10000	0	-10000	0	0
CALM1	0.011	0.026	-10000	0	-10000	0	0
JUN	0.012	0.026	-10000	0	-10000	0	0
mol:Ca2+	-0.008	0.011	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.01	0.013	-10000	0	-10000	0	0
FOSL1	-0.001	0.1	-10000	0	-0.36	31	31
CREM	0.027	0.006	-10000	0	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.024	0.12	-10000	0	-0.34	5	5
FOS	-0.009	0.093	-10000	0	-0.39	21	21
IFNG	-0.11	0.22	0.35	1	-0.52	55	56
AP-1/NFAT1-c-4	-0.077	0.21	-10000	0	-0.57	27	27
FASLG	-0.08	0.19	0.35	1	-0.53	29	30
NFAT1-c-4/ICER1	-0.023	0.07	-10000	0	-10000	0	0
IL2RA	-0.086	0.2	0.35	1	-0.54	36	37
FKBP12/FK506	0.019	0.007	-10000	0	-10000	0	0
CSF2	-0.11	0.21	-10000	0	-0.53	49	49
JunB/Fra1/NFAT1-c-4	-0.01	0.1	-10000	0	-0.3	7	7
IL4	-0.082	0.18	-10000	0	-0.5	28	28
IL2	-0.017	0.16	-10000	0	-0.84	15	15
IL3	-0.025	0.14	-10000	0	-0.59	19	19
FKBP1A	0.025	0.009	-10000	0	-10000	0	0
BATF3	0.025	0.033	-10000	0	-0.35	3	3
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.026	0.021	-10000	0	-0.35	1	1

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.056	0.18	-10000	0	-0.42	78	78
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.019	0.099	0.39	3	-10000	0	3
IL27/IL27R/JAK1	0.047	0.12	0.4	1	-0.41	1	2
TBX21	0.008	0.12	0.34	2	-0.43	1	3
IL12B	0.018	0.043	-10000	0	-0.36	5	5
IL12A	-0.011	0.06	-10000	0	-0.27	21	21
IL6ST	0.016	0.041	-10000	0	-0.4	3	3
IL27RA/JAK1	0.019	0.041	-10000	0	-10000	0	0
IL27	0.005	0.071	-10000	0	-0.36	14	14
TYK2	0.016	0.023	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.24	0.51	0.43	4	-1.2	85	89
T-helper 2 cell differentiation	0.019	0.099	0.39	3	-10000	0	3
T cell proliferation during immune response	0.019	0.099	0.39	3	-10000	0	3
MAPKKK cascade	-0.019	0.099	-10000	0	-0.39	3	3
STAT3	0.028	0.004	-10000	0	-10000	0	0
STAT2	0.028	0.004	-10000	0	-10000	0	0
STAT1	0.02	0.059	-10000	0	-0.35	10	10
IL12RB1	0.022	0.041	-10000	0	-0.38	4	4
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	0.002	0.13	0.34	2	-0.42	6	8
IL27/IL27R/JAK2/TYK2	-0.019	0.098	-10000	0	-0.39	3	3
positive regulation of T cell mediated cytotoxicity	-0.019	0.099	-10000	0	-0.39	3	3
STAT1 (dimer)	0.062	0.18	0.42	39	-10000	0	39
JAK2	0.014	0.022	-10000	0	-10000	0	0
JAK1	0.029	0.005	-10000	0	-10000	0	0
STAT2 (dimer)	-0.013	0.1	-10000	0	-0.4	2	2
T cell proliferation	-0.07	0.12	-10000	0	-0.4	16	16
IL12/IL12R/TYK2/JAK2	-0.047	0.21	-10000	0	-0.78	28	28
IL17A	-0.23	0.51	0.43	4	-1.2	84	88
mast cell activation	0.019	0.099	0.39	3	-10000	0	3
IFNG	-0.011	0.037	-10000	0	-0.1	10	10
T cell differentiation	-0.002	0.006	0.01	2	-0.017	12	14
STAT3 (dimer)	-0.014	0.1	-10000	0	-0.37	4	4
STAT5A (dimer)	-0.014	0.1	-10000	0	-0.37	4	4
STAT4 (dimer)	-0.016	0.1	-10000	0	-0.36	4	4
STAT4	0.024	0.038	-10000	0	-0.35	4	4
T cell activation	-0.005	0.005	0.048	2	-10000	0	2
IL27R/JAK2/TYK2	0.024	0.065	-10000	0	-10000	0	0
GATA3	0.014	0.12	0.65	12	-10000	0	12
IL18	0.001	0.026	-10000	0	-0.25	4	4
positive regulation of mast cell cytokine production	-0.013	0.1	-10000	0	-0.36	4	4
IL27/EBI3	0.013	0.074	-10000	0	-0.26	24	24
IL27RA	0.004	0.034	-10000	0	-10000	0	0
IL6	-0.095	0.22	-10000	0	-0.44	108	108
STAT5A	0.028	0.004	-10000	0	-10000	0	0
monocyte differentiation	-0.001	0.002	-10000	0	-10000	0	0
IL2	-0.011	0.026	-10000	0	-10000	0	0
IL1B	-0.022	0.077	-10000	0	-0.25	41	41
EBI3	0.011	0.064	-10000	0	-0.37	10	10
TNF	-0.008	0.052	-10000	0	-0.25	18	18

×

IGF1 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.028	0.004	-10000	0	-10000	0	0
PTK2	0.024	0.01	-10000	0	-10000	0	0
CRKL	-0.006	0.063	0.16	2	-0.21	24	26
GRB2/SOS1/SHC	0.053	0.015	-10000	0	-10000	0	0
HRAS	0.026	0.007	-10000	0	-10000	0	0
IRS1/Crk	0.002	0.065	-10000	0	-0.2	25	25
IGF-1R heterotetramer/IGF1/PTP1B	0.016	0.078	-10000	0	-0.2	41	41
AKT1	-0.013	0.07	0.19	21	-0.32	1	22
BAD	-0.014	0.067	0.18	21	-0.31	1	22
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.005	0.06	0.16	2	-0.21	20	22
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.008	0.07	0.21	2	-0.21	25	27
RAF1	0.004	0.08	0.3	3	-0.42	4	7
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.033	0.077	-10000	0	-0.2	23	23
YWHAZ	0.023	0.011	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.008	0.074	-10000	0	-0.19	49	49
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
RPS6KB1	-0.013	0.07	0.18	22	-0.32	1	23
GNB2L1	0.027	0.005	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	0.005	0.075	0.33	5	-0.33	1	6
PXN	0.027	0.005	-10000	0	-10000	0	0
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.04	0.008	-10000	0	-10000	0	0
HRAS/GTP	0.009	0.061	-10000	0	-0.3	1	1
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.045	0.081	-10000	0	-0.34	1	1
IGF-1R heterotetramer	0.016	0.041	-10000	0	-0.4	2	2
IGF-1R heterotetramer/IGF1/IRS/Nck	0.022	0.076	-10000	0	-0.21	25	25
Crk/p130 Cas/Paxillin	0.032	0.074	0.22	2	-0.19	19	21
IGF1R	0.016	0.041	-10000	0	-0.4	2	2
IGF1	-0.021	0.13	-10000	0	-0.38	51	51
IRS2/Crk	-0.004	0.07	0.16	1	-0.2	30	31
PI3K	0.029	0.076	-10000	0	-0.2	20	20
apoptosis	0.011	0.058	0.27	1	-0.25	3	4
HRAS/GDP	0.02	0.005	-10000	0	-10000	0	0
PRKCD	-0.012	0.083	-10000	0	-0.31	22	22
RAF1/14-3-3 E	0.013	0.082	0.31	3	-0.35	5	8
BAD/14-3-3	-0.012	0.06	0.26	3	-0.29	1	4
PRKCZ	-0.012	0.069	0.18	21	-0.32	1	22
Crk/p130 Cas/Paxillin/FAK1	0.017	0.059	-10000	0	-0.26	1	1
PTPN1	0.022	0.012	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.011	0.091	-10000	0	-0.3	29	29
BCAR1	0.027	0.006	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.033	0.08	-10000	0	-0.2	22	22
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.028	0.003	-10000	0	-10000	0	0
IRS1/NCK2	0.01	0.072	-10000	0	-0.2	25	25
GRB10	0.026	0.02	-10000	0	-0.35	1	1
PTPN11	-0.007	0.064	0.16	2	-0.21	25	27
IRS1	-0.005	0.07	-10000	0	-0.19	47	47
IRS2	-0.013	0.07	0.16	1	-0.21	35	36
IGF-1R heterotetramer/IGF1	0.001	0.1	-10000	0	-0.27	49	49
GRB2	0.027	0.005	-10000	0	-10000	0	0
PDPK1	0.003	0.072	0.19	19	-0.33	1	20
YWHAE	0.026	0.008	-10000	0	-10000	0	0
PRKD1	-0.017	0.094	-10000	0	-0.33	27	27
SHC1	0.027	0.005	-10000	0	-10000	0	0

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.082	0.18	-10000	0	-0.38	110	110
oxygen homeostasis	0	0	-10000	0	-10000	0	0
TCEB2	0.026	0.007	-10000	0	-10000	0	0
TCEB1	0.024	0.01	-10000	0	-10000	0	0
HIF1A/p53	0.022	0.056	-10000	0	-0.24	14	14
HIF1A	0.006	0.051	-10000	0	-0.26	13	13
COPS5	0.025	0.009	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.064	0.036	-10000	0	-10000	0	0
FIH (dimer)	0.027	0.006	-10000	0	-10000	0	0
CDKN2A	-0.088	0.17	-10000	0	-0.35	121	121
ARNT/IPAS	-0.039	0.13	-10000	0	-0.27	103	103
HIF1AN	0.027	0.006	-10000	0	-10000	0	0
GNB2L1	0.027	0.005	-10000	0	-10000	0	0
HIF1A/ARNT	0.021	0.057	-10000	0	-0.25	14	14
CUL2	0.027	0.006	-10000	0	-10000	0	0
OS9	0.027	0.005	-10000	0	-10000	0	0
RACK1/Elongin B/Elongin C	0.046	0.023	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF1A/Hsp90	0.022	0.058	-10000	0	-0.25	13	13
PHD1-3/OS9	0.063	0.028	-10000	0	-0.21	1	1
HIF1A/RACK1/Elongin B/Elongin C	0.037	0.058	-10000	0	-0.24	7	7
VHL	0.028	0.004	-10000	0	-10000	0	0
HSP90AA1	0.025	0.027	-10000	0	-0.35	2	2
HIF1A/JAB1	0.018	0.057	0.18	1	-0.25	14	15
EGLN3	0.026	0.021	-10000	0	-0.38	1	1
EGLN2	0.027	0.006	-10000	0	-10000	0	0
EGLN1	0.027	0.005	-10000	0	-10000	0	0
TP53	0.026	0.008	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.028	0.078	-10000	0	-0.5	8	8
ARNT	0.027	0.006	-10000	0	-10000	0	0
ARD1A	0	0	-10000	0	-10000	0	0
RBX1	0.027	0.005	-10000	0	-10000	0	0
HIF1A/p19ARF	-0.029	0.096	-10000	0	-0.31	18	18

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.01	0.08	-10000	0	-0.35	19	19
ANTXR2	0.024	0.035	-10000	0	-0.38	3	3
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.003	0.01	-10000	0	-0.044	22	22
monocyte activation	0.001	0.079	-10000	0	-0.35	18	18
MAP2K2	-0.018	0.14	-10000	0	-0.56	24	24
MAP2K1	-0.005	0.009	-10000	0	-10000	0	0
MAP2K7	-0.005	0.009	-10000	0	-10000	0	0
MAP2K6	-0.008	0.024	-10000	0	-0.19	6	6
CYAA	-0.014	0.038	-10000	0	-0.17	22	22
MAP2K4	-0.005	0.009	-10000	0	-10000	0	0
IL1B	-0.02	0.055	0.19	3	-0.17	40	43
Channel	0.022	0.05	-10000	0	-0.19	22	22
NLRP1	-0.008	0.024	-10000	0	-0.17	7	7
CALM1	0.027	0.005	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.003	0.072	-10000	0	-0.38	14	14
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.003	0.01	0.044	22	-10000	0	22
MAPK3	-0.005	0.009	-10000	0	-10000	0	0
MAPK1	-0.005	0.009	-10000	0	-10000	0	0
PGR	-0.022	0.055	-10000	0	-0.19	38	38
PA/Cellular Receptors	0.023	0.056	-10000	0	-0.21	22	22
apoptosis	-0.003	0.01	-10000	0	-0.044	22	22
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.023	0.045	-10000	0	-0.16	22	22
macrophage activation	-0.007	0.009	-10000	0	-10000	0	0
TNF	0.01	0.08	-10000	0	-0.36	18	18
VCAM1	0.005	0.069	-10000	0	-0.34	14	14
platelet activation	-0.003	0.072	-10000	0	-0.38	14	14
MAPKKK cascade	0.003	0.016	-10000	0	-0.067	6	6
IL18	-0.006	0.024	0.19	1	-0.17	4	5
negative regulation of macrophage activation	-0.003	0.01	-10000	0	-0.044	22	22
LEF	-0.003	0.01	-10000	0	-0.045	22	22
CASP1	-0.003	0.014	-10000	0	-0.089	6	6
mol:cAMP	-0.003	0.072	-10000	0	-0.38	14	14
necrosis	-0.003	0.01	-10000	0	-0.044	22	22
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.022	0.047	-10000	0	-0.18	22	22
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.003	0.028	0.11	15	-0.1	1	16
BUB1B	-0.006	0.057	0.12	6	-0.14	23	29
PLK1	0.013	0.029	0.083	26	-0.096	1	27
PLK1S1	0.016	0.036	0.12	7	-0.2	5	12
KIF2A	0.009	0.029	0.16	5	-10000	0	5
regulation of mitotic centrosome separation	0.013	0.029	0.083	26	-0.096	1	27
GOLGA2	0.027	0.006	-10000	0	-10000	0	0
Hec1/SPC24	0.033	0.051	-10000	0	-0.18	13	13
WEE1	0.014	0.062	0.18	2	-0.33	10	12
cytokinesis	0.006	0.058	0.15	2	-0.22	8	10
PP2A-alpha B56	0.035	0.091	-10000	0	-0.53	7	7
AURKA	0.015	0.025	0.11	3	-10000	0	3
PICH/PLK1	0.009	0.039	0.15	2	-0.19	4	6
CENPE	-0.05	0.087	-10000	0	-0.17	120	120
RhoA/GTP	0.02	0.004	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.01	0.03	0.16	5	-10000	0	5
PPP2CA	0.026	0.007	-10000	0	-10000	0	0
FZR1	0.026	0.007	-10000	0	-10000	0	0
TPX2	0.017	0.035	0.1	31	-10000	0	31
PAK1	0.028	0.006	-10000	0	-10000	0	0
SPC24	0.024	0.033	-10000	0	-0.35	3	3
FBXW11	0.027	0.006	-10000	0	-10000	0	0
CLSPN	-0.013	0.053	0.15	1	-0.23	7	8
GORASP1	0.027	0.005	-10000	0	-10000	0	0
metaphase	0.001	0.003	0.016	15	-0.009	1	16
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.006	0.016	0.046	28	-0.047	1	29
G2 phase of mitotic cell cycle	0	0.003	0.013	12	-10000	0	12
STAG2	0.027	0.005	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.006	0.088	-10000	0	-0.49	12	12
spindle elongation	0.013	0.029	0.083	26	-0.096	1	27
ODF2	0.028	0.007	-10000	0	-10000	0	0
BUB1	0.006	0.087	-10000	0	-0.57	7	7
TPT1	0.014	0.031	0.1	10	-0.19	5	15
CDC25C	0.003	0.06	-10000	0	-0.25	19	19
CDC25B	0.022	0.029	-10000	0	-0.35	2	2
SGOL1	0.003	0.028	0.1	1	-0.11	15	16
RHOA	0.027	0.006	-10000	0	-10000	0	0
CCNB1/CDK1	0.031	0.039	-10000	0	-10000	0	0
CDC14B	0.007	0.003	-10000	0	-10000	0	0
CDC20	0.021	0.049	-10000	0	-0.35	7	7
PLK1/PBIP1	0.009	0.023	0.092	3	-0.16	1	4
mitosis	-0.001	0.004	0.017	12	-10000	0	12
FBXO5	0.011	0.034	0.13	13	-0.12	3	16
CDC2	0.001	0.002	-10000	0	-0.01	7	7
NDC80	0.013	0.071	-10000	0	-0.35	15	15
metaphase plate congression	0	0.066	-10000	0	-0.23	29	29
ERCC6L	0.008	0.044	-10000	0	-0.21	4	4
NLP/gamma Tubulin	0.009	0.018	0.076	11	-0.08	1	12
microtubule cytoskeleton organization	0.014	0.031	0.1	10	-0.19	5	15
G2/M transition DNA damage checkpoint	0	0.002	0.018	3	-10000	0	3
PPP1R12A	0.027	0.019	-10000	0	-0.35	1	1
interphase	0	0.002	0.018	3	-10000	0	3
PLK1/PRC1-2	0.026	0.061	-10000	0	-0.19	17	17
GRASP65/GM130/RAB1/GTP/PLK1	0.05	0.03	-10000	0	-10000	0	0
RAB1A	0.028	0.003	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.014	0.03	0.081	36	-0.075	1	37
mitotic prometaphase	0	0.005	0.017	29	-10000	0	29
proteasomal ubiquitin-dependent protein catabolic process	0.02	0.031	0.17	1	-0.26	1	2
microtubule-based process	0.015	0.054	0.13	2	-0.17	25	27
Golgi organization	0.013	0.029	0.083	26	-0.096	1	27
Cohesin/SA2	0.025	0.024	0.11	3	-10000	0	3
PPP1CB/MYPT1	0.04	0.017	-10000	0	-0.25	1	1
KIF20A	0.004	0.091	-10000	0	-0.35	25	25
APC/C/CDC20	0.024	0.041	0.12	3	-0.21	7	10
PPP2R1A	0.027	0.006	-10000	0	-10000	0	0
chromosome segregation	0.009	0.023	0.091	3	-0.16	1	4
PRC1	0.021	0.046	-10000	0	-0.35	6	6
ECT2	-0.014	0.1	0.21	31	-0.18	81	112
C13orf34	0.012	0.026	0.075	28	-10000	0	28
NUDC	0	0.066	-10000	0	-0.23	29	29
regulation of attachment of spindle microtubules to kinetochore	-0.006	0.056	0.12	6	-0.14	23	29
spindle assembly	0.011	0.026	0.094	16	-10000	0	16
spindle stabilization	0.016	0.036	0.12	7	-0.2	5	12
APC/C/HCDH1	0.024	0.008	-10000	0	-10000	0	0
MKLP2/PLK1	0.015	0.054	0.13	2	-0.17	25	27
CCNB1	0.024	0.033	-10000	0	-0.35	3	3
PPP1CB	0.028	0.003	-10000	0	-10000	0	0
BTRC	0.027	0.006	-10000	0	-10000	0	0
ROCK2	0.016	0.046	0.16	1	-0.28	5	6
TUBG1	0.013	0.022	0.15	1	-0.18	2	3
G2/M transition of mitotic cell cycle	0.002	0.03	-10000	0	-10000	0	0
MLF1IP	0.005	0.013	-10000	0	-0.25	1	1
INCENP	0.028	0.004	-10000	0	-10000	0	0

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.004	0.091	-9999	-0.35	25	25
mol:S1P	0.001	0.001	-9999	-10000	0	0
S1P1/S1P/Gi	-0.031	0.11	-9999	-0.28	36	36
GNAO1	-0.054	0.16	-9999	-0.38	82	82
S1P/S1P3/G12/G13	0.046	0.03	-9999	-0.2	4	4
AKT1	-0.016	0.11	-9999	-0.44	21	21
AKT3	0.006	0.071	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.004	0.091	-9999	-0.35	25	25
GNAI2	0.028	0.006	-9999	-10000	0	0
GNAI3	0.028	0.005	-9999	-10000	0	0
GNAI1	0.02	0.054	-9999	-0.38	7	7
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.024	0.039	-9999	-0.37	4	4
S1PR2	0.026	0.019	-9999	-0.35	1	1
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	-0.028	0.12	-9999	-0.37	25	25
MAPK3	-0.033	0.11	-9999	-0.34	25	25
MAPK1	-0.029	0.11	-9999	-0.36	20	20
JAK2	-0.03	0.13	-9999	-0.37	29	29
CXCR4	-0.044	0.12	-9999	-0.34	29	29
FLT1	0.027	0.02	-9999	-0.35	1	1
RhoA/GDP	0.02	0.004	-9999	-10000	0	0
Rac1/GDP	0.019	0.006	-9999	-10000	0	0
SRC	-0.03	0.11	-9999	-0.36	23	23
S1P/S1P3/Gi	-0.028	0.12	-9999	-0.37	25	25
RAC1	0.026	0.008	-9999	-10000	0	0
RhoA/GTP	-0.024	0.12	-9999	-0.33	28	28
VEGFA	0.026	0.021	-9999	-0.35	1	1
S1P/S1P2/Gi	-0.029	0.12	-9999	-0.35	26	26
VEGFR1 homodimer/VEGFA homodimer	0.039	0.022	-9999	-0.24	1	1
RHOA	0.027	0.006	-9999	-10000	0	0
S1P/S1P3/Gq	0.018	0.04	-9999	-0.23	8	8
GNAQ	0.027	0.006	-9999	-10000	0	0
GNAZ	0.002	0.1	-9999	-0.38	26	26
G12/G13	0.038	0.013	-9999	-10000	0	0
GNA14	0.02	0.053	-9999	-0.38	7	7
GNA15	0.022	0.042	-9999	-0.35	5	5
GNA12	0.026	0.008	-9999	-10000	0	0
GNA13	0.027	0.005	-9999	-10000	0	0
GNA11	0.026	0.007	-9999	-10000	0	0
Rac1/GTP	-0.023	0.12	-9999	-0.34	26	26

×

JNK signaling in the CD4+ TCR pathway

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
LAT/GRAP2/SLP76/HPK1	0.047	0.074	-10000	0	-0.24	21	21
MAP4K1	0.013	0.073	-10000	0	-0.37	14	14
MAP3K8	0.026	0.02	-10000	0	-0.35	1	1
PRKCB	0.003	0.096	-10000	0	-0.38	24	24
DBNL	0.026	0.007	-10000	0	-10000	0	0
CRKL	0.027	0.006	-10000	0	-10000	0	0
MAP3K1	0.008	0.06	-10000	0	-0.31	9	9
JUN	-0.032	0.19	-10000	0	-0.57	42	42
MAP3K7	0.009	0.062	-10000	0	-0.32	9	9
GRAP2	0.016	0.067	-10000	0	-0.38	11	11
CRK	0.026	0.008	-10000	0	-10000	0	0
MAP2K4	0.008	0.066	0.27	1	-0.32	8	9
LAT	0.026	0.019	-10000	0	-0.35	1	1
LCP2	0.027	0.006	-10000	0	-10000	0	0
MAPK8	-0.031	0.2	-10000	0	-0.6	42	42
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.017	0.064	-10000	0	-0.32	9	9
LAT/GRAP2/SLP76/HPK1/HIP-55	0.056	0.07	-10000	0	-0.27	10	10

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.004	0.091	-10000	0	-0.35	25	25
Jak2/Leptin Receptor	-0.032	0.14	-10000	0	-0.41	25	25
PTP1B/AKT1	0.001	0.073	-10000	0	-0.32	4	4
FYN	0.027	0.005	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.008	0.074	-10000	0	-0.32	5	5
EGFR	0.016	0.058	-10000	0	-0.39	8	8
EGF/EGFR	-0.014	0.087	-10000	0	-0.29	9	9
CSF1	0.026	0.019	-10000	0	-0.35	1	1
AKT1	0.027	0.006	-10000	0	-10000	0	0
INSR	0.027	0.007	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.014	0.084	-10000	0	-0.4	4	4
Insulin Receptor/Insulin	0.012	0.072	-10000	0	-0.29	2	2
HCK	0.024	0.01	-10000	0	-10000	0	0
CRK	0.026	0.008	-10000	0	-10000	0	0
TYK2	-0.008	0.071	0.32	1	-0.31	5	6
EGF	-0.018	0.12	-10000	0	-0.36	44	44
YES1	0.026	0.007	-10000	0	-10000	0	0
CAV1	0.003	0.088	0.22	13	-0.32	7	20
TXN	0.027	0.006	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	0.007	0.081	-10000	0	-0.32	4	4
cell migration	0.008	0.074	0.32	5	-10000	0	5
STAT3	0.027	0.004	-10000	0	-10000	0	0
PRLR	-0.012	0.12	-10000	0	-0.38	36	36
ITGA2B	0.014	0.067	-10000	0	-0.36	13	13
CSF1R	0.023	0.041	-10000	0	-0.38	4	4
Prolactin Receptor/Prolactin	-0.002	0.098	-10000	0	-0.27	45	45
FGR	0.027	0.006	-10000	0	-10000	0	0
PTP1B/p130 Cas	0	0.073	-10000	0	-0.3	5	5
Crk/p130 Cas	0.006	0.077	-10000	0	-0.3	4	4
DOK1	-0.01	0.076	-10000	0	-0.34	5	5
JAK2	-0.043	0.14	-10000	0	-0.4	31	31
Jak2/Leptin Receptor/Leptin	-0.022	0.1	-10000	0	-0.37	4	4
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
PTPN1	-0.008	0.074	-10000	0	-0.33	5	5
LYN	0.025	0.009	-10000	0	-10000	0	0
CDH2	-0.005	0.11	-10000	0	-0.37	32	32
SRC	0.015	0.079	-10000	0	-0.51	7	7
ITGB3	0.023	0.043	-10000	0	-0.36	5	5
CAT1/PTP1B	-0.042	0.15	0.25	16	-0.42	23	39
CAPN1	0.027	0.005	-10000	0	-10000	0	0
CSK	0.027	0.005	-10000	0	-10000	0	0
PI3K	0.03	0.065	-10000	0	-0.3	1	1
mol:H2O2	0.001	0.004	-10000	0	-10000	0	0
STAT3 (dimer)	-0.015	0.096	-10000	0	-0.35	3	3
negative regulation of transcription	-0.043	0.13	-10000	0	-0.39	32	32
FCGR2A	0.022	0.046	-10000	0	-0.35	6	6
FER	0.025	0.009	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	0.027	0.06	-10000	0	-0.25	18	18
BLK	-0.041	0.15	-10000	0	-0.38	66	66
Insulin Receptor/Insulin/Shc	0.046	0.017	-10000	0	-10000	0	0
RHOA	0.027	0.006	-10000	0	-10000	0	0
LEPR	0.025	0.034	-10000	0	-0.37	3	3
BCAR1	0.027	0.006	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.027	0.005	-10000	0	-10000	0	0
mol:NADPH	0	0.003	-10000	0	-10000	0	0
TRPV6	-0.057	0.17	0.28	4	-0.45	34	38
PRL	0.003	0.07	-10000	0	-0.36	14	14
SOCS3	0.018	0.12	-10000	0	-1	5	5
SPRY2	0.026	0.022	-10000	0	-0.4	1	1
Insulin Receptor/Insulin/IRS1	0.046	0.021	-10000	0	-0.24	1	1
CSF1/CSF1R	0.006	0.081	-10000	0	-0.32	3	3
Ras protein signal transduction	0.004	0.066	0.51	6	-10000	0	6
IRS1	0.027	0.021	-10000	0	-0.38	1	1
INS	0.015	0.012	-10000	0	-10000	0	0
LEP	-0.015	0.12	-10000	0	-0.38	41	41
STAT5B	-0.015	0.087	-10000	0	-0.34	12	12
STAT5A	-0.015	0.087	-10000	0	-0.34	12	12
GRB2	0.027	0.005	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.01	0.088	-10000	0	-0.3	6	6
CSN2	-0.008	0.072	-10000	0	-0.42	1	1
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
LAT	0.015	0.067	-10000	0	-0.44	6	6
YBX1	0.035	0.007	-10000	0	-10000	0	0
LCK	0.017	0.062	-10000	0	-0.35	11	11
SHC1	0.027	0.005	-10000	0	-10000	0	0
NOX4	-0.14	0.19	-10000	0	-0.35	179	179

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.004	0.091	-10000	0	-0.35	25	25
alphaV beta3 Integrin	0.035	0.033	-10000	0	-0.25	5	5
PTK2	0.014	0.074	-10000	0	-0.36	7	7
positive regulation of JNK cascade	0.012	0.084	-10000	0	-0.32	5	5
CDC42/GDP	0.038	0.12	0.3	2	-0.39	10	12
Rac1/GDP	0.035	0.11	0.31	2	-0.39	10	12
RAP1B	0.027	0.007	-10000	0	-10000	0	0
RAP1A	0.027	0.005	-10000	0	-10000	0	0
CTNNB1	0.027	0.006	-10000	0	-10000	0	0
CDC42/GTP	0.026	0.11	-10000	0	-0.4	5	5
nectin-3/I-afadin	0.027	0.061	-10000	0	-0.27	16	16
RAPGEF1	0.022	0.1	0.3	5	-0.41	6	11
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.007	0.098	-10000	0	-0.45	7	7
PDGFB-D/PDGFRB	0.004	0.091	-10000	0	-0.35	25	25
TLN1	-0.001	0.02	-10000	0	-10000	0	0
Rap1/GTP	0.014	0.072	-10000	0	-0.3	6	6
IQGAP1	0.026	0.007	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.048	0.018	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.027	0.061	-10000	0	-0.27	16	16
PVR	0.026	0.02	-10000	0	-0.35	1	1
Necl-5(dimer)	0.026	0.02	-10000	0	-0.35	1	1
mol:GDP	0.027	0.13	0.32	2	-0.48	10	12
MLLT4	0.026	0.007	-10000	0	-10000	0	0
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
PI3K	0.043	0.081	-10000	0	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.026	0.056	-10000	0	-0.25	16	16
positive regulation of lamellipodium assembly	0.017	0.088	-10000	0	-0.31	11	11
PVRL1	0.012	0.074	-10000	0	-0.35	16	16
PVRL3	0.011	0.08	-10000	0	-0.38	16	16
PVRL2	0.027	0.006	-10000	0	-10000	0	0
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
CDH1	0.018	0.06	-10000	0	-0.38	9	9
CLDN1	-0.24	0.17	-10000	0	-0.35	288	288
JAM-A/CLDN1	-0.12	0.12	-10000	0	-0.3	15	15
SRC	0.007	0.11	-10000	0	-0.49	8	8
ITGB3	0.023	0.042	-10000	0	-0.36	5	5
nectin-1(dimer)/I-afadin/I-afadin	0.026	0.056	-10000	0	-0.25	16	16
FARP2	0.022	0.14	-10000	0	-0.56	5	5
RAC1	0.026	0.008	-10000	0	-10000	0	0
CTNNA1	0.027	0.006	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.039	0.056	-10000	0	-0.23	15	15
nectin-1/I-afadin	0.026	0.056	-10000	0	-0.25	16	16
nectin-2/I-afadin	0.038	0.013	-10000	0	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0.033	0.013	-10000	0	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.033	0.071	-10000	0	-0.23	25	25
CDC42/GTP/IQGAP1/filamentous actin	0.034	0.012	-10000	0	-10000	0	0
F11R	0.027	0.005	-10000	0	-10000	0	0
positive regulation of filopodium formation	0.012	0.084	-10000	0	-0.32	5	5
alphaV/beta3 Integrin/Talin	0.033	0.059	0.2	15	-10000	0	15
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.038	0.013	-10000	0	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.038	0.013	-10000	0	-10000	0	0
PIP5K1C	0.001	0.031	-10000	0	-0.33	1	1
VAV2	0.027	0.14	-10000	0	-0.52	9	9
RAP1/GDP	0.04	0.1	0.27	2	-0.36	8	10
ITGAV	0.026	0.007	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.041	0.053	-10000	0	-0.23	13	13
nectin-3(dimer)/I-afadin/I-afadin	0.027	0.061	-10000	0	-0.27	16	16
Rac1/GTP	0.025	0.11	-10000	0	-0.38	11	11
PTPRM	0.006	0.036	-10000	0	-0.36	1	1
E-cadherin/beta catenin/alpha catenin	0.051	0.067	-10000	0	-10000	0	0
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.026	0.007	-10000	0	-10000	0	0

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.011	0.014	-10000	0	-0.25	1	1
MAP4K4	0.015	0.054	0.2	5	-0.39	2	7
BAG4	0.025	0.009	-10000	0	-10000	0	0
PKC zeta/ceramide	-0.004	0.067	-10000	0	-0.2	36	36
NFKBIA	0.028	0.004	-10000	0	-10000	0	0
BIRC3	0.021	0.047	-10000	0	-0.36	6	6
BAX	-0.006	0.068	-10000	0	-0.36	12	12
RIPK1	0.026	0.007	-10000	0	-10000	0	0
AKT1	-0.005	0.011	-10000	0	-10000	0	0
BAD	-0.02	0.065	0.2	3	-0.2	38	41
SMPD1	0.014	0.067	0.18	13	-0.27	9	22
RB1	-0.009	0.073	0.19	18	-0.2	30	48
FADD/Caspase 8	0.023	0.076	0.22	17	-0.48	3	20
MAP2K4	-0.022	0.057	-10000	0	-0.2	21	21
NSMAF	0.025	0.009	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.017	0.062	0.19	7	-0.24	8	15
EGF	-0.016	0.12	-10000	0	-0.36	44	44
mol:ceramide	-0.02	0.066	-10000	0	-0.21	38	38
MADD	0.027	0.005	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.01	0.014	-10000	0	-0.25	1	1
ASAH1	0.025	0.01	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.009	0.072	0.19	18	-0.2	30	48
cell proliferation	-0.012	0.085	0.19	2	-0.29	7	9
BID	-0.004	0.16	-10000	0	-0.67	19	19
MAP3K1	-0.021	0.061	-10000	0	-0.2	37	37
EIF2A	-0.014	0.069	0.17	17	-0.27	6	23
TRADD	0.027	0.006	-10000	0	-10000	0	0
CRADD	0.028	0.004	-10000	0	-10000	0	0
MAPK3	-0.015	0.061	0.19	3	-0.26	4	7
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.017	0.062	0.19	3	-0.26	6	9
Cathepsin D/ceramide	-0.004	0.069	-10000	0	-0.2	38	38
FADD	0.021	0.062	0.21	17	-0.39	2	19
KSR1	-0.018	0.062	0.2	4	-0.2	36	40
MAPK8	-0.016	0.071	-10000	0	-0.28	12	12
PRKRA	-0.02	0.065	0.19	3	-0.2	38	41
PDGFA	0.025	0.02	-10000	0	-0.35	1	1
TRAF2	0.027	0.006	-10000	0	-10000	0	0
IGF1	-0.022	0.13	-10000	0	-0.37	51	51
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.02	0.066	-10000	0	-0.21	38	38
CTSD	0.027	0.006	-10000	0	-10000	0	0
regulation of nitric oxide biosynthetic process	0.04	0.009	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.012	0.09	0.21	2	-0.31	7	9
PRKCD	0.027	0.005	-10000	0	-10000	0	0
PRKCZ	0.026	0.007	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.01	0.014	-10000	0	-0.25	1	1
RelA/NF kappa B1	0.04	0.009	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.027	0.005	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.017	0.041	-10000	0	-0.41	2	2
TNFR1A/BAG4/TNF-alpha	0.036	0.054	-10000	0	-0.21	16	16
mol:Sphingosine-1-phosphate	0.011	0.013	-10000	0	-0.25	1	1
MAP2K1	-0.018	0.06	0.18	4	-0.24	7	11
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.027	0.005	-10000	0	-10000	0	0
CYCS	0.004	0.05	0.22	1	-0.21	8	9
TNFRSF1A	0.027	0.006	-10000	0	-10000	0	0
NFKB1	0.027	0.005	-10000	0	-10000	0	0
TNFR1A/BAG4	0.036	0.015	-10000	0	-10000	0	0
EIF2AK2	-0.019	0.064	0.18	7	-0.2	24	31
TNF-alpha/TNFR1A/FAN	0.036	0.055	-10000	0	-0.21	16	16
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.027	0.053	-10000	0	-0.32	4	4
MAP2K2	-0.019	0.059	0.19	3	-0.24	6	9
SMPD3	0	0.091	0.26	3	-0.3	27	30
TNF	0.01	0.08	-10000	0	-0.36	18	18
PKC zeta/PAR4	0.038	0.012	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	0.004	0.056	0.19	5	-0.19	3	8
NF kappa B1/RelA/I kappa B alpha	0.072	0.029	-10000	0	-10000	0	0
AIFM1	-0.001	0.057	0.14	4	-0.23	9	13
BCL2	0.024	0.022	-10000	0	-0.38	1	1

×

Paxillin-independent events mediated by a4b1 and a4b7

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.017	0.025	-10000	0	-0.27	1	1
CRKL	0.027	0.006	-10000	0	-10000	0	0
Rac1/GDP	0.019	0.006	-10000	0	-10000	0	0
DOCK1	0.027	0.006	-10000	0	-10000	0	0
ITGA4	0.025	0.033	-10000	0	-0.35	3	3
alpha4/beta7 Integrin/MAdCAM1	-0.013	0.12	-10000	0	-0.21	112	112
EPO	0.013	0.055	-10000	0	-0.35	9	9
alpha4/beta7 Integrin	0.036	0.03	-10000	0	-0.25	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.026	0.008	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.036	0.03	-10000	0	-0.25	4	4
EPO/EPOR (dimer)	0.028	0.042	-10000	0	-0.24	9	9
lamellipodium assembly	0.016	0.069	-10000	0	-0.5	4	4
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
PI3K	0.036	0.014	-10000	0	-10000	0	0
ARF6	0.027	0.006	-10000	0	-10000	0	0
JAK2	0.016	0.032	-10000	0	-0.27	2	2
PXN	0.027	0.005	-10000	0	-10000	0	0
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
MADCAM1	-0.086	0.18	-10000	0	-0.38	113	113
cell adhesion	-0.014	0.12	-10000	0	-0.21	112	112
CRKL/CBL	0.038	0.012	-10000	0	-10000	0	0
ITGB1	0.026	0.02	-10000	0	-0.35	1	1
SRC	0.013	0.038	0.18	10	-10000	0	10
ITGB7	0.026	0.021	-10000	0	-0.38	1	1
RAC1	0.026	0.008	-10000	0	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.047	0.038	-10000	0	-0.21	7	7
p130Cas/Crk/Dock1	0.042	0.05	-10000	0	-10000	0	0
VCAM1	0.025	0.033	-10000	0	-0.35	3	3
RHOA	0.027	0.006	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.062	0.034	-10000	0	-0.19	4	4
BCAR1	-0.009	0.036	0.18	9	-10000	0	9
EPOR	0.027	0.005	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.027	0.006	-10000	0	-10000	0	0
GIT1	0.028	0.004	-10000	0	-10000	0	0
Rac1/GTP	0.016	0.07	-10000	0	-0.52	4	4

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.006	0.11	0.22	5	-0.49	12	17
BAG4	0.025	0.009	-10000	0	-10000	0	0
BAD	0.009	0.043	0.16	7	-0.18	7	14
NFKBIA	0.028	0.004	-10000	0	-10000	0	0
BIRC3	0.021	0.047	-10000	0	-0.36	6	6
BAX	0.012	0.049	0.18	14	-0.18	6	20
EnzymeConsortium:3.1.4.12	0.005	0.026	0.07	9	-0.1	11	20
IKBKB	0.017	0.11	0.25	9	-0.5	9	18
MAP2K2	0.009	0.048	0.19	12	-0.25	2	14
MAP2K1	0.009	0.049	0.19	13	-0.24	2	15
SMPD1	0.006	0.034	0.1	6	-0.17	8	14
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.021	0.11	0.22	19	-0.52	10	29
MAP2K4	0.009	0.035	0.15	4	-0.24	2	6
protein ubiquitination	0.014	0.11	0.24	5	-0.5	11	16
EnzymeConsortium:2.7.1.37	0.009	0.052	0.19	14	-0.28	2	16
response to UV	0	0.001	0.002	15	-0.002	2	17
RAF1	0.01	0.051	0.2	12	-0.22	4	16
CRADD	0.028	0.004	-10000	0	-10000	0	0
mol:ceramide	0.01	0.043	0.12	9	-0.17	10	19
I-kappa-B-alpha/RELA/p50/ubiquitin	0.036	0.008	-10000	0	-10000	0	0
MADD	0.027	0.005	-10000	0	-10000	0	0
MAP3K1	0.008	0.04	0.14	5	-0.2	5	10
TRADD	0.027	0.006	-10000	0	-10000	0	0
RELA/p50	0.027	0.005	-10000	0	-10000	0	0
MAPK3	0.011	0.053	0.19	13	-0.29	2	15
MAPK1	0.01	0.055	0.19	12	-0.28	3	15
p50/RELA/I-kappa-B-alpha	0.04	0.009	-10000	0	-10000	0	0
FADD	0.014	0.11	0.21	19	-0.5	10	29
KSR1	0.011	0.049	0.19	11	-0.21	5	16
MAPK8	0.007	0.041	0.21	4	-0.22	2	6
TRAF2	0.027	0.006	-10000	0	-10000	0	0
response to radiation	0	0	0.002	4	-10000	0	4
CHUK	0.011	0.098	0.22	3	-0.48	10	13
TNF R/SODD	0.036	0.015	-10000	0	-10000	0	0
TNF	0.01	0.08	-10000	0	-0.36	18	18
CYCS	0.021	0.052	0.16	23	-0.17	3	26
IKBKG	0.013	0.11	0.24	6	-0.49	10	16
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.006	0.11	-10000	0	-0.54	11	11
RELA	0.027	0.005	-10000	0	-10000	0	0
RIPK1	0.026	0.007	-10000	0	-10000	0	0
AIFM1	0.017	0.048	0.15	21	-0.17	3	24
TNF/TNF R/SODD	0.036	0.054	-10000	0	-0.21	16	16
TNFRSF1A	0.027	0.006	-10000	0	-10000	0	0
response to heat	0	0	0.002	4	-10000	0	4
CASP8	0.023	0.084	-10000	0	-0.62	6	6
NSMAF	0.017	0.11	0.21	27	-0.47	11	38
response to hydrogen peroxide	0	0.001	0.002	15	-0.002	2	17
BCL2	0.024	0.022	-10000	0	-0.38	1	1

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.066	0.14	-10000	0	-0.54	17	17
MKNK1	0.028	0.004	-10000	0	-10000	0	0
MAPK14	-0.045	0.096	-10000	0	-0.26	19	19
ATF2/c-Jun	-0.03	0.066	-10000	0	-0.34	1	1
MAPK11	-0.048	0.097	-10000	0	-0.28	20	20
MITF	-0.052	0.11	-10000	0	-0.38	16	16
MAPKAPK5	-0.047	0.093	-10000	0	-0.32	11	11
KRT8	-0.047	0.097	-10000	0	-0.35	12	12
MAPKAPK3	0.027	0.006	-10000	0	-10000	0	0
MAPKAPK2	0.027	0.006	-10000	0	-10000	0	0
p38alpha-beta/CK2	-0.06	0.13	-10000	0	-0.37	18	18
CEBPB	-0.038	0.083	-10000	0	-0.33	7	7
SLC9A1	-0.046	0.091	-10000	0	-0.32	9	9
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	-0.046	0.094	-10000	0	-0.32	9	9
p38alpha-beta/MNK1	-0.035	0.11	-10000	0	-0.3	18	18
JUN	-0.03	0.065	-10000	0	-0.34	1	1
PPARGC1A	-0.067	0.12	-10000	0	-0.38	24	24
USF1	-0.046	0.093	-10000	0	-0.32	11	11
RAB5/GDP/GDI1	-0.03	0.072	-10000	0	-0.24	9	9
NOS2	-0.12	0.19	-10000	0	-0.51	30	30
DDIT3	-0.047	0.093	-10000	0	-0.28	22	22
RAB5A	0.028	0.004	-10000	0	-10000	0	0
HSPB1	-0.034	0.092	0.28	11	-0.3	11	22
p38alpha-beta/HBP1	-0.035	0.11	-10000	0	-0.3	18	18
CREB1	-0.04	0.091	-10000	0	-0.34	11	11
RAB5/GDP	0.02	0.003	-10000	0	-10000	0	0
EIF4E	-0.046	0.084	-10000	0	-0.29	7	7
RPS6KA4	-0.045	0.092	-10000	0	-0.28	21	21
PLA2G4A	-0.052	0.092	-10000	0	-0.34	11	11
GDI1	-0.046	0.092	-10000	0	-0.32	10	10
TP53	-0.063	0.1	-10000	0	-0.34	20	20
RPS6KA5	-0.047	0.093	-10000	0	-0.32	11	11
ESR1	-0.056	0.1	-10000	0	-0.34	16	16
HBP1	0.027	0.006	-10000	0	-10000	0	0
MEF2C	-0.05	0.098	-10000	0	-0.34	14	14
MEF2A	-0.044	0.09	-10000	0	-0.32	10	10
EIF4EBP1	-0.043	0.097	-10000	0	-0.38	10	10
KRT19	-0.046	0.1	-10000	0	-0.36	14	14
ELK4	-0.045	0.092	-10000	0	-0.32	10	10
ATF6	-0.046	0.093	-10000	0	-0.32	11	11
ATF1	-0.041	0.091	-10000	0	-0.34	11	11
p38alpha-beta/MAPKAPK2	-0.036	0.11	-10000	0	-0.3	17	17
p38alpha-beta/MAPKAPK3	-0.036	0.11	-10000	0	-0.3	18	18

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	-0.027	0.14	-10000	0	-0.41	45	45
NFATC2	0.01	0.1	-10000	0	-0.52	1	1
NFATC3	-0.013	0.065	-10000	0	-0.27	7	7
CD40LG	-0.14	0.25	-10000	0	-0.8	21	21
ITCH	0.021	0.034	-10000	0	-10000	0	0
CBLB	0.024	0.036	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.12	0.21	-10000	0	-0.71	20	20
JUNB	0.027	0.005	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0.031	0.043	-10000	0	-0.24	8	8
T cell anergy	0.026	0.066	-10000	0	-0.35	9	9
TLE4	0.002	0.091	-10000	0	-0.64	5	5
Jun/NFAT1-c-4/p21SNFT	-0.05	0.19	-10000	0	-0.76	10	10
AP-1/NFAT1-c-4	-0.15	0.27	-10000	0	-0.86	19	19
IKZF1	-0.001	0.085	-10000	0	-0.37	4	4
T-helper 2 cell differentiation	-0.024	0.11	-10000	0	-0.56	2	2
AP-1/NFAT1	-0.023	0.11	-10000	0	-0.39	6	6
CALM1	0.032	0.029	-10000	0	-10000	0	0
EGR2	-0.023	0.16	-10000	0	-1	6	6
EGR3	-0.03	0.2	-10000	0	-1.1	11	11
NFAT1/FOXP3	-0.013	0.15	-10000	0	-0.46	22	22
EGR1	0.015	0.065	-10000	0	-0.38	10	10
JUN	-0.018	0.045	-10000	0	-10000	0	0
EGR4	-0.042	0.15	-10000	0	-0.36	74	74
mol:Ca2+	0.005	0.023	-10000	0	-10000	0	0
GBP3	0.003	0.082	-10000	0	-0.62	3	3
FOSL1	-0.001	0.1	-10000	0	-0.36	31	31
NFAT1-c-4/MAF/IRF4	-0.018	0.17	-10000	0	-0.78	9	9
DGKA	0.006	0.063	-10000	0	-10000	0	0
CREM	0.026	0.006	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.026	0.17	-10000	0	-0.77	10	10
CTLA4	-0.042	0.16	-10000	0	-0.46	40	40
NFAT1-c-4 (dimer)/EGR1	-0.027	0.18	-10000	0	-0.85	10	10
NFAT1-c-4 (dimer)/EGR4	-0.051	0.18	-10000	0	-0.78	10	10
FOS	-0.037	0.095	-10000	0	-0.4	21	21
IFNG	-0.061	0.15	-10000	0	-0.56	4	4
T cell activation	-0.023	0.12	-10000	0	-0.59	1	1
MAF	0.021	0.05	-10000	0	-0.38	6	6
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.023	0.14	0.65	13	-10000	0	13
TNF	-0.061	0.18	-10000	0	-0.79	10	10
FASLG	-0.053	0.29	-10000	0	-1.2	20	20
TBX21	0	0.065	-10000	0	-0.39	6	6
BATF3	0.025	0.033	-10000	0	-0.35	3	3
PRKCQ	0.01	0.08	-10000	0	-0.39	15	15
PTPN1	0.007	0.065	-10000	0	-10000	0	0
NFAT1-c-4/ICER1	-0.022	0.16	-10000	0	-0.79	9	9
GATA3	0.017	0.059	-10000	0	-0.35	10	10
T-helper 1 cell differentiation	-0.06	0.15	-10000	0	-0.55	4	4
IL2RA	-0.095	0.19	-10000	0	-0.66	16	16
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	0.005	0.062	-10000	0	-0.36	1	1
E2F1	0.019	0.056	-10000	0	-0.35	9	9
PPARG	0.023	0.045	-10000	0	-0.38	5	5
SLC3A2	0.007	0.065	-10000	0	-0.36	1	1
IRF4	0.012	0.074	-10000	0	-0.38	14	14
PTGS2	-0.15	0.26	-10000	0	-0.74	34	34
CSF2	-0.18	0.28	-10000	0	-0.73	39	39
JunB/Fra1/NFAT1-c-4	-0.024	0.17	-10000	0	-0.74	10	10
IL4	-0.026	0.11	-10000	0	-0.58	2	2
IL5	-0.14	0.24	-10000	0	-0.77	19	19
IL2	-0.024	0.13	-10000	0	-0.6	1	1
IL3	-0.04	0.13	-10000	0	-0.61	11	11
RNF128	0.018	0.077	-10000	0	-0.46	10	10
NFATC1	-0.023	0.14	-10000	0	-0.66	13	13
CDK4	0.011	0.087	0.59	2	-10000	0	2
PTPRK	0.007	0.063	-10000	0	-0.36	1	1
IL8	-0.21	0.29	-10000	0	-0.73	44	44
POU2F1	0.026	0.021	-10000	0	-0.35	1	1

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.026	0.007	-9999	-10000	0	0
EGFR	0.017	0.057	-9999	-0.38	8	8
EGF/EGFR	0.01	0.084	-9999	-0.18	59	59
EGF/EGFR dimer/SHC/GRB2/SOS1	0.04	0.083	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.017	0.062	-9999	-0.35	11	11
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.016	0.12	-9999	-0.36	44	44
EGF/EGFR dimer/SHC	0.018	0.084	-9999	-0.21	45	45
mol:GDP	0.034	0.08	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.02	0.05	-9999	-0.36	7	7
GRB2/SOS1	0.04	0.008	-9999	-10000	0	0
HRAS/GTP	0.019	0.069	-9999	-10000	0	0
SHC1	0.027	0.005	-9999	-10000	0	0
HRAS/GDP	0.032	0.078	-9999	-10000	0	0
FRAP1	-0.028	0.051	-9999	-0.19	3	3
EGF/EGFR dimer	0.001	0.093	-9999	-0.25	48	48
SOS1	0.028	0.003	-9999	-10000	0	0
GRB2	0.027	0.005	-9999	-10000	0	0
ETA receptor/Endothelin-1	0.025	0.06	-9999	-0.25	18	18

×

FOXM1 transcription factor network

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
NFATC3	-0.037	0.31	0.57	1	-1	8	9
PLK1	0.003	0.19	-10000	0	-1	11	11
BIRC5	0.008	0.16	-10000	0	-1	7	7
HSPA1B	-0.036	0.31	-10000	0	-1.1	7	7
MAP2K1	0.02	0.042	-10000	0	-10000	0	0
BRCA2	-0.033	0.31	-10000	0	-1	9	9
FOXM1	-0.051	0.35	-10000	0	-1.1	14	14
XRCC1	-0.035	0.31	0.57	1	-1	7	8
FOXM1B/p19	-0.091	0.33	-10000	0	-1.1	13	13
Cyclin D1/CDK4	-0.044	0.3	-10000	0	-0.94	10	10
CDC2	-0.041	0.32	-10000	0	-0.98	14	14
TGFA	-0.044	0.3	-10000	0	-0.92	9	9
SKP2	-0.025	0.31	0.55	2	-1.1	7	9
CCNE1	0.01	0.072	-10000	0	-0.36	15	15
CKS1B	-0.039	0.31	-10000	0	-0.94	14	14
RB1	-0.001	0.18	-10000	0	-0.91	6	6
FOXM1C/SP1	-0.04	0.33	-10000	0	-1	13	13
AURKB	-0.034	0.26	-10000	0	-0.92	30	30
CENPF	-0.072	0.33	0.57	1	-1	13	14
CDK4	0.022	0.023	-10000	0	-10000	0	0
MYC	-0.033	0.26	-10000	0	-0.93	6	6
CHEK2	0.021	0.041	-10000	0	-10000	0	0
ONECUT1	-0.048	0.32	-10000	0	-0.94	15	15
CDKN2A	-0.089	0.17	-10000	0	-0.35	121	121
LAMA4	-0.039	0.31	-10000	0	-1.1	7	7
FOXM1B/HNF6	-0.058	0.34	-10000	0	-1.1	13	13
FOS	-0.072	0.38	-10000	0	-1.1	28	28
SP1	0.027	0.007	-10000	0	-10000	0	0
CDC25B	-0.025	0.31	0.54	1	-1	7	8
response to radiation	0.004	0.023	-10000	0	-10000	0	0
CENPB	-0.023	0.3	0.54	1	-1	7	8
CENPA	-0.042	0.32	-10000	0	-1.1	8	8
NEK2	-0.047	0.32	0.57	1	-1	13	14
HIST1H2BA	-0.041	0.31	-10000	0	-1	8	8
CCNA2	0.026	0.015	-10000	0	-10000	0	0
EP300	0.027	0.005	-10000	0	-10000	0	0
CCNB1/CDK1	-0.049	0.33	-10000	0	-1.2	8	8
CCNB2	-0.039	0.31	-10000	0	-1.1	7	7
CCNB1	-0.041	0.32	-10000	0	-1.1	8	8
ETV5	-0.032	0.31	0.57	1	-1.1	8	9
ESR1	-0.055	0.36	-10000	0	-1.2	19	19
CCND1	-0.052	0.3	-10000	0	-0.96	10	10
GSK3A	0.02	0.037	-10000	0	-10000	0	0
Cyclin A-E1/CDK1-2	0.037	0.063	-10000	0	-0.22	9	9
CDK2	0.025	0.015	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.003	0.027	-10000	0	-10000	0	0
FOXM1B/Cbp/p300	-0.032	0.32	-10000	0	-1	12	12
GAS1	-0.11	0.44	0.57	1	-1.1	50	51
MMP2	-0.04	0.31	0.57	1	-1.1	8	9
RB1/FOXM1C	-0.034	0.3	-10000	0	-0.99	9	9
CREBBP	0.026	0.007	-10000	0	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	0.021	0.067	-10000	0	-0.25	23	23
CRKL	0.013	0.11	0.29	4	-0.47	12	16
mol:PIP3	-0.004	0.058	-10000	0	-0.82	2	2
AKT1	-0.007	0.054	-10000	0	-0.72	2	2
PTK2B	0.025	0.009	-10000	0	-10000	0	0
RAPGEF1	0.015	0.11	0.3	6	-0.46	11	17
RANBP10	0.027	0.007	-10000	0	-10000	0	0
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
HGF/MET/SHIP2	0.028	0.076	-10000	0	-0.22	33	33
MAP3K5	0.013	0.11	0.29	4	-0.43	13	17
HGF/MET/CIN85/CBL/ENDOPHILINS	0.041	0.075	-10000	0	-0.24	6	6
AP1	0.015	0.072	0.17	2	-0.24	21	23
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.027	0.005	-10000	0	-10000	0	0
apoptosis	-0.035	0.22	-10000	0	-0.71	39	39
STAT3 (dimer)	0.008	0.057	-10000	0	-0.27	8	8
GAB1/CRKL/SHP2/PI3K	0.039	0.11	0.31	2	-0.45	9	11
INPP5D	0.025	0.034	-10000	0	-0.36	3	3
CBL/CRK	0.027	0.11	0.29	5	-0.45	11	16
PTPN11	0.028	0.004	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.023	0.011	-10000	0	-10000	0	0
PTEN	0.026	0.008	-10000	0	-10000	0	0
ELK1	0.003	0.11	0.31	29	-0.32	1	30
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	0.006	0.047	-10000	0	-0.22	8	8
PAK1	-0.003	0.061	-10000	0	-0.69	2	2
HGF/MET/RANBP10	0.029	0.074	-10000	0	-0.22	32	32
HRAS	-0.002	0.11	-10000	0	-0.47	13	13
DOCK1	0.016	0.11	0.28	9	-0.45	11	20
GAB1	0.009	0.095	0.24	1	-0.48	10	11
CRK	0.011	0.11	0.29	5	-0.46	12	17
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.001	0.1	-10000	0	-0.43	16	16
JUN	0.028	0.004	-10000	0	-10000	0	0
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.006	0.041	-10000	0	-0.2	7	7
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
cell morphogenesis	0.034	0.11	0.3	27	-0.44	3	30
GRB2/SHC	0.02	0.059	-10000	0	-0.21	4	4
FOS	0.006	0.091	-10000	0	-0.38	21	21
GLMN	0.003	0.006	-10000	0	-10000	0	0
cell motility	0.003	0.1	0.31	29	-0.32	1	30
HGF/MET/MUC20	0.014	0.069	-10000	0	-0.22	33	33
cell migration	0.02	0.058	-10000	0	-0.21	4	4
GRB2	0.027	0.005	-10000	0	-10000	0	0
CBL	0.027	0.006	-10000	0	-10000	0	0
MET/RANBP10	0.022	0.065	-10000	0	-0.25	22	22
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.011	0.044	-10000	0	-0.24	7	7
MET/MUC20	0.005	0.061	-10000	0	-0.24	23	23
RAP1B	0.02	0.11	0.27	14	-0.43	11	25
RAP1A	0.014	0.1	0.29	7	-0.43	11	18
HGF/MET/RANBP9	0.028	0.076	-10000	0	-0.22	33	33
RAF1	0.001	0.11	-10000	0	-0.45	12	12
STAT3	0.008	0.057	-10000	0	-0.27	8	8
cell proliferation	0.015	0.084	0.3	9	-0.34	7	16
RPS6KB1	0.007	0.031	-10000	0	-0.34	2	2
MAPK3	-0.004	0.12	0.62	11	-10000	0	11
MAPK1	0.006	0.15	0.64	17	-10000	0	17
RANBP9	0.027	0.006	-10000	0	-10000	0	0
MAPK8	0.021	0.11	0.3	5	-0.44	10	15
SRC	0.007	0.037	-10000	0	-0.25	3	3
PI3K	0.019	0.055	-10000	0	-0.22	2	2
MET/Glomulin	-0.005	0.06	-10000	0	-0.21	25	25
SOS1	0.028	0.003	-10000	0	-10000	0	0
MAP2K1	0	0.1	-10000	0	-0.44	10	10
MET	0.005	0.088	-10000	0	-0.36	23	23
MAP4K1	0.012	0.12	0.3	3	-0.44	16	19
PTK2	0.024	0.01	-10000	0	-10000	0	0
MAP2K2	0.001	0.1	-10000	0	-0.44	10	10
BAD	-0.007	0.054	-10000	0	-0.69	2	2
MAP2K4	0.012	0.1	0.28	4	-0.42	10	14
SHP2/GRB2/SOS1/GAB1	0.025	0.099	-10000	0	-0.44	9	9
INPPL1	0.026	0.02	-10000	0	-0.35	1	1
PXN	0.027	0.005	-10000	0	-10000	0	0
SH3KBP1	0.028	0.004	-10000	0	-10000	0	0
HGS	-0.007	0.037	-10000	0	-0.19	5	5
PLCgamma1/PKC	0.017	0.008	-10000	0	-10000	0	0
HGF	0.014	0.07	-10000	0	-0.37	13	13
RASA1	0.025	0.008	-10000	0	-10000	0	0
NCK1	0.027	0.005	-10000	0	-10000	0	0
PTPRJ	0.027	0.019	-10000	0	-0.35	1	1
NCK/PLCgamma1	0.026	0.052	-10000	0	-0.22	2	2
PDPK1	-0.006	0.058	-10000	0	-0.76	2	2
HGF/MET/SHIP	0.027	0.078	-10000	0	-0.22	36	36

×

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	-0.001	0.033	0.23	5	-0.19	3	8
RFC1	-0.002	0.026	0.22	2	-0.19	2	4
PRKDC	0.011	0.057	0.22	26	-0.19	3	29
RIPK1	0.027	0.008	-10000	0	-10000	0	0
CASP7	0.002	0.11	-10000	0	-0.63	10	10
FASLG/FAS/FADD/FAF1	0.009	0.053	0.18	4	-0.25	6	10
MAP2K4	-0.018	0.14	0.32	2	-0.41	27	29
mol:ceramide	0.007	0.073	-10000	0	-0.28	10	10
GSN	-0.004	0.037	0.24	3	-0.24	5	8
FASLG/FAS/FADD/FAF1/Caspase 8	0.007	0.065	-10000	0	-0.27	9	9
FAS	0.022	0.016	-10000	0	-10000	0	0
BID	-0.014	0.023	-10000	0	-10000	0	0
MAP3K1	-0.001	0.1	0.3	2	-0.44	11	13
MAP3K7	0.026	0.008	-10000	0	-10000	0	0
RB1	0.006	0.047	0.22	17	-0.19	1	18
CFLAR	0.029	0.005	-10000	0	-10000	0	0
HGF/MET	0.019	0.092	-10000	0	-0.23	45	45
ARHGDIB	-0.002	0.031	0.22	4	-0.19	4	8
FADD	0.022	0.017	-10000	0	-10000	0	0
actin filament polymerization	0.014	0.054	0.25	4	-0.24	3	7
NFKB1	-0.007	0.11	-10000	0	-0.61	10	10
MAPK8	-0.034	0.17	0.31	3	-0.49	41	44
DFFA	-0.001	0.03	0.22	4	-0.19	3	7
DNA fragmentation during apoptosis	-0.011	0.048	0.22	3	-10000	0	3
FAS/FADD/MET	0.028	0.064	-10000	0	-0.21	23	23
CFLAR/RIP1	0.04	0.012	-10000	0	-10000	0	0
FAIM3	0.011	0.078	-10000	0	-0.35	18	18
FAF1	0.021	0.02	-10000	0	-10000	0	0
PARP1	-0.003	0.025	0.22	1	-0.19	4	5
DFFB	-0.002	0.028	0.22	3	-0.19	2	5
CHUK	-0.007	0.097	-10000	0	-0.57	8	8
FASLG	0.007	0.077	-10000	0	-0.38	15	15
FAS/FADD	0.031	0.023	-10000	0	-10000	0	0
HGF	0.014	0.07	-10000	0	-0.37	13	13
LMNA	-0.012	0.043	0.19	3	-10000	0	3
CASP6	-0.003	0.02	-10000	0	-0.19	2	2
CASP10	0.022	0.026	-10000	0	-0.38	1	1
CASP3	0	0.017	-10000	0	-10000	0	0
PTPN13	0.01	0.081	-10000	0	-0.38	17	17
CASP8	-0.013	0.037	0.16	18	-10000	0	18
IL6	-0.093	0.35	-10000	0	-1.1	41	41
MET	0.005	0.088	-10000	0	-0.36	23	23
ICAD/CAD	-0.001	0.041	0.36	4	-10000	0	4
FASLG/FAS/FADD/FAF1/Caspase 10	0.006	0.073	-10000	0	-0.29	10	10
activation of caspase activity by cytochrome c	-0.014	0.023	-10000	0	-10000	0	0
PAK2	0.004	0.046	0.22	15	-0.19	3	18
BCL2	0.024	0.022	-10000	0	-0.38	1	1

×

Ras signaling in the CD4+ TCR 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
ERK1-2/ELK1	0.021	0.12	0.25	1	-0.41	12	13
MAP3K8	0.026	0.02	-10000	0	-0.36	1	1
FOS	0.011	0.1	0.26	1	-0.38	13	14
PRKCA	0.025	0.012	-10000	0	-10000	0	0
PTPN7	0.02	0.048	-10000	0	-0.36	6	6
HRAS	0.026	0.007	-10000	0	-10000	0	0
PRKCB	0.001	0.097	-10000	0	-0.38	24	24
NRAS	0.027	0.005	-10000	0	-10000	0	0
RAS family/GTP	0.043	0.023	-10000	0	-10000	0	0
MAPK3	0.015	0.092	-10000	0	-0.51	9	9
MAP2K1	0.003	0.098	-10000	0	-0.36	22	22
ELK1	0.025	0.014	-10000	0	-10000	0	0
BRAF	0.001	0.084	-10000	0	-0.34	22	22
mol:GTP	0	0.001	-10000	0	-0.005	23	23
MAPK1	0.011	0.096	-10000	0	-0.42	14	14
RAF1	0.001	0.084	-10000	0	-0.34	22	22
KRAS	0.025	0.009	-10000	0	-10000	0	0

×

Caspase cascade in apoptosis

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
TOP1	-0.006	0.085	0.2	1	-0.34	13	14
ACTA1	-0.019	0.074	0.19	1	-0.27	10	11
NUMA1	-0.006	0.098	0.22	1	-0.38	14	15
SPTAN1	-0.013	0.073	0.24	4	-0.27	6	10
LIMK1	-0.012	0.079	0.3	4	-0.27	6	10
BIRC3	0.021	0.047	-10000	0	-0.36	6	6
BIRC2	0.027	0.006	-10000	0	-10000	0	0
BAX	0.027	0.006	-10000	0	-10000	0	0
CASP10	-0.024	0.053	-10000	0	-0.21	30	30
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.027	0.004	-10000	0	-10000	0	0
PTK2	-0.009	0.11	-10000	0	-0.43	14	14
DIABLO	0.027	0.005	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.012	0.072	0.24	4	-0.27	6	10
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.028	0.004	-10000	0	-10000	0	0
GSN	-0.018	0.075	-10000	0	-0.29	10	10
MADD	0.027	0.005	-10000	0	-10000	0	0
TFAP2A	-0.048	0.18	-10000	0	-0.64	27	27
BID	-0.003	0.035	-10000	0	-0.18	8	8
MAP3K1	-0.024	0.12	-10000	0	-0.4	32	32
TRADD	0.027	0.006	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.039	0.01	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.013	0.073	0.35	1	-0.26	8	9
CASP9	0.027	0.006	-10000	0	-10000	0	0
DNA repair	-0.003	0.036	0.19	2	-10000	0	2
neuron apoptosis	-0.03	0.19	-10000	0	-0.63	34	34
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.009	0.093	-10000	0	-0.38	10	10
APAF1	0.028	0.004	-10000	0	-10000	0	0
CASP6	-0.011	0.17	-10000	0	-0.9	13	13
TRAF2	0.027	0.006	-10000	0	-10000	0	0
ICAD/CAD	-0.011	0.079	0.35	6	-0.27	5	11
CASP7	-0.005	0.069	-10000	0	-0.41	4	4
KRT18	0	0.11	-10000	0	-0.56	12	12
apoptosis	-0.012	0.1	0.43	3	-0.42	14	17
DFFA	-0.013	0.075	0.27	4	-0.27	7	11
DFFB	-0.015	0.07	-10000	0	-0.27	6	6
PARP1	0.003	0.036	-10000	0	-0.19	2	2
actin filament polymerization	0.014	0.078	0.3	2	-0.27	5	7
TNF	0.01	0.08	-10000	0	-0.36	18	18
CYCS	0.01	0.036	0.16	3	-0.17	1	4
SATB1	-0.012	0.16	-10000	0	-0.84	13	13
SLK	-0.015	0.071	0.34	2	-0.27	6	8
p15 BID/BAX	0.014	0.046	0.2	1	-0.25	2	3
CASP2	0.009	0.055	0.21	3	-0.33	5	8
JNK cascade	0.024	0.12	0.4	32	-10000	0	32
CASP3	-0.017	0.072	0.21	1	-0.28	8	9
LMNB2	-0.001	0.12	0.23	2	-0.47	18	20
RIPK1	0.026	0.007	-10000	0	-10000	0	0
CASP4	0.027	0.006	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	0.063	0.036	-10000	0	-10000	0	0
negative regulation of DNA binding	-0.046	0.18	-10000	0	-0.62	27	27
stress fiber formation	-0.014	0.071	0.34	2	-0.27	6	8
GZMB	-0.006	0.068	-10000	0	-0.25	29	29
CASP1	0.012	0.02	-10000	0	-0.14	7	7
LMNB1	-0.007	0.14	0.23	2	-0.59	17	19
APP	-0.031	0.19	-10000	0	-0.64	34	34
TNFRSF1A	0.027	0.006	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.007	0.001	-10000	0	-10000	0	0
VIM	-0.012	0.1	0.32	3	-0.43	15	18
LMNA	0.014	0.093	0.23	2	-0.44	10	12
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.012	0.056	-10000	0	-0.32	6	6
LRDD	0	0	-10000	0	-10000	0	0
SREBF1	-0.015	0.069	0.22	1	-0.27	6	7
APAF-1/Caspase 9	0.009	0.088	-10000	0	-0.63	7	7
nuclear fragmentation during apoptosis	-0.006	0.096	0.22	1	-0.38	14	15
CFL2	-0.014	0.079	0.27	5	-0.27	4	9
GAS2	-0.023	0.078	-10000	0	-0.28	10	10
positive regulation of apoptosis	0.003	0.13	0.23	2	-0.52	16	18
PRF1	0.023	0.041	-10000	0	-0.39	4	4

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	0.011	0.005	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.034	0.021	-10000	0	-10000	0	0
CDKN1B	0.01	0.065	-10000	0	-0.3	12	12
CDKN1A	0.009	0.067	-10000	0	-0.3	11	11
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.025	0.009	-10000	0	-10000	0	0
FOXO3	0.009	0.068	0.2	2	-0.3	12	14
AKT1	0.005	0.058	-10000	0	-0.32	8	8
BAD	0.028	0.004	-10000	0	-10000	0	0
AKT3	0.013	0.009	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.007	0.069	-10000	0	-0.3	13	13
AKT1/ASK1	0.033	0.08	-10000	0	-0.29	12	12
BAD/YWHAZ	0.046	0.023	-10000	0	-10000	0	0
RICTOR	0.025	0.009	-10000	0	-10000	0	0
RAF1	0.028	0.004	-10000	0	-10000	0	0
JNK cascade	-0.031	0.078	0.28	12	-10000	0	12
TSC1	0.01	0.064	-10000	0	-0.3	10	10
YWHAZ	0.023	0.011	-10000	0	-10000	0	0
AKT1/RAF1	0.035	0.085	0.27	1	-0.3	14	15
EP300	0.027	0.005	-10000	0	-10000	0	0
mol:GDP	0.01	0.071	-10000	0	-0.31	13	13
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.011	0.061	-10000	0	-0.31	9	9
YWHAQ	0.028	0.004	-10000	0	-10000	0	0
TBC1D4	0.004	0.028	0.22	2	-0.19	6	8
MAP3K5	0.027	0.005	-10000	0	-10000	0	0
MAPKAP1	0.027	0.005	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.038	0.084	0.3	8	-0.2	20	28
YWHAH	0.027	0.005	-10000	0	-10000	0	0
AKT1S1	0.007	0.069	-10000	0	-0.3	13	13
CASP9	0.012	0.056	-10000	0	-0.28	8	8
YWHAB	0.022	0.011	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.036	0.087	0.3	5	-0.3	9	14
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.044	0.029	-10000	0	-0.21	2	2
YWHAE	0.026	0.008	-10000	0	-10000	0	0
SRC	0.024	0.01	-10000	0	-10000	0	0
AKT2/p21CIP1	0.012	0.072	0.26	3	-0.33	6	9
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.005	0.068	-10000	0	-0.32	14	14
CHUK	0.007	0.069	-10000	0	-0.3	13	13
BAD/BCL-XL	0.029	0.075	0.26	1	-0.5	1	2
mTORC2	0.032	0.012	-10000	0	-10000	0	0
AKT2	0.014	0.004	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.041	0.11	0.24	22	-0.43	8	30
PDPK1	0.027	0.007	-10000	0	-10000	0	0
MDM2	0.014	0.074	0.2	7	-0.3	12	19
MAPKKK cascade	-0.035	0.084	0.29	14	-0.27	1	15
MDM2/Cbp/p300	0.048	0.089	0.3	5	-0.37	2	7
TSC1/TSC2	0.01	0.059	0.31	1	-0.31	7	8
proteasomal ubiquitin-dependent protein catabolic process	0.045	0.086	0.29	5	-0.36	2	7
glucose import	-0.041	0.099	0.2	15	-0.2	98	113
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.012	0.063	0.18	5	-0.47	2	7
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.042	0.098	0.2	13	-0.2	98	111
GSK3A	0.008	0.068	-10000	0	-0.3	13	13
FOXO1	0.008	0.072	-10000	0	-0.3	14	14
GSK3B	0.008	0.07	-10000	0	-0.3	13	13
SFN	0.015	0.067	-10000	0	-0.37	12	12
G1/S transition of mitotic cell cycle	0.019	0.081	0.24	8	-0.3	9	17
p27Kip1/14-3-3 family	0.033	0.057	-10000	0	-0.39	2	2
PRKACA	0.027	0.005	-10000	0	-10000	0	0
KPNA1	0.027	0.005	-10000	0	-10000	0	0
HSP90AA1	0.025	0.027	-10000	0	-0.35	2	2
YWHAG	0.026	0.007	-10000	0	-10000	0	0
RHEB	0.027	0.006	-10000	0	-10000	0	0
CREBBP	0.026	0.007	-10000	0	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	-0.009	0.011	-10000	0	-0.23	1	1
SNTA1	0.013	0.067	-10000	0	-0.38	11	11
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	-0.009	0.011	-10000	0	-0.23	1	1
MAPK12	-0.008	0.031	-10000	0	-0.19	11	11
CCND1	0.007	0.03	-10000	0	-0.32	2	2
p38 gamma/SNTA1	0.009	0.051	0.19	6	-0.2	14	20
MAP2K3	0.026	0.008	-10000	0	-10000	0	0
PKN1	0.027	0.005	-10000	0	-10000	0	0
G2/M transition checkpoint	-0.008	0.031	-10000	0	-0.19	11	11
MAP2K6	0	0.026	-10000	0	-0.21	6	6
MAPT	-0.05	0.12	0.22	1	-0.28	81	82
MAPK13	0.011	0.015	-10000	0	-0.27	1	1
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.007	0.001	-10000	0	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.027	0.005	-10000	0	-10000	0	0
HDAC3	0.027	0.006	-10000	0	-10000	0	0
VDR	0.027	0.005	-10000	0	-10000	0	0
Cbp/p300/PCAF	0.048	0.033	-10000	0	-0.23	4	4
EP300	0.027	0.005	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.004	0.056	-10000	0	-0.35	5	5
KAT2B	0.024	0.041	-10000	0	-0.38	4	4
MAPK14	0.027	0.006	-10000	0	-10000	0	0
AKT1	-0.009	0.061	0.22	4	-0.24	6	10
RAR alpha/9cRA/Cyclin H	-0.001	0.075	-10000	0	-0.32	2	2
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.002	0.061	0.23	1	-0.28	9	10
CDC2	0	0	-10000	0	-10000	0	0
response to UV	0.001	0	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.006	0.062	-10000	0	-0.31	2	2
NCOR2	0.027	0.005	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.02	0.004	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA	-0.047	0.098	-10000	0	-0.42	6	6
NCOA2	0.024	0.022	-10000	0	-0.38	1	1
NCOA3	0.023	0.011	-10000	0	-10000	0	0
NCOA1	0.028	0.003	-10000	0	-10000	0	0
VDR/VDR/DNA	0.027	0.005	-10000	0	-10000	0	0
RARG	0.027	0.02	-10000	0	-0.35	1	1
RAR gamma1/9cRA	0.035	0.015	-10000	0	-0.2	1	1
MAPK3	0.028	0.005	-10000	0	-10000	0	0
MAPK1	0.027	0.006	-10000	0	-10000	0	0
MAPK8	0.028	0.005	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.053	0.096	-10000	0	-0.38	7	7
RARA	-0.025	0.057	-10000	0	-0.22	9	9
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.001	0.058	-10000	0	-0.28	9	9
PRKCA	0.029	0.005	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.054	0.1	0.35	1	-0.39	6	7
RXRG	-0.15	0.17	-10000	0	-0.34	161	161
RXRA	-0.019	0.06	-10000	0	-0.27	4	4
RXRB	-0.045	0.082	-10000	0	-0.28	8	8
VDR/Vit D3/DNA	0.02	0.004	-10000	0	-10000	0	0
RBP1	0.013	0.073	-10000	0	-0.36	15	15
CRBP1/9-cic-RA	0.01	0.051	-10000	0	-0.25	15	15
RARB	0.026	0.035	-10000	0	-0.38	3	3
PRKCG	-0.13	0.19	-10000	0	-0.35	174	174
MNAT1	0.027	0.005	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.051	0.095	0.26	2	-0.4	9	11
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.041	0.098	0.21	1	-0.36	11	12
proteasomal ubiquitin-dependent protein catabolic process	0.006	0.078	0.25	2	-0.3	7	9
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.054	0.1	0.35	1	-0.38	7	8
positive regulation of DNA binding	-0.007	0.067	-10000	0	-0.31	2	2
NRIP1	-0.05	0.097	-10000	0	-10000	0	0
RXRs/RARs	-0.056	0.1	-10000	0	-0.36	13	13
RXRs/RXRs/DNA/9cRA	-0.062	0.09	-10000	0	-0.38	8	8
PRKACA	0.027	0.005	-10000	0	-10000	0	0
CDK7	0.026	0.008	-10000	0	-10000	0	0
TFIIH	0.05	0.019	-10000	0	-10000	0	0
RAR alpha/9cRA	0.01	0.07	0.2	1	-0.25	2	3
CCNH	0.026	0.008	-10000	0	-10000	0	0
CREBBP	0.026	0.007	-10000	0	-10000	0	0
RAR gamma2/9cRA	0.046	0.024	-10000	0	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.035	0.011	-10000	0	-10000	0	0
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0.026	0.007	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.022	0.049	-10000	0	-0.38	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.025	0.009	-10000	0	-10000	0	0
RAC1-CDC42/GTP/PAK family	-0.007	0.062	-10000	0	-0.18	47	47
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.026	0.007	-10000	0	-10000	0	0
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	0.027	0.005	-10000	0	-10000	0	0
FYN	0.027	0.005	-10000	0	-10000	0	0
MAP3K12	0.027	0.006	-10000	0	-10000	0	0
FGR	0.027	0.006	-10000	0	-10000	0	0
p38 alpha/TAB1	-0.036	0.097	-10000	0	-0.4	21	21
PRKG1	0.022	0.044	-10000	0	-0.37	5	5
DUSP8	0.025	0.029	-10000	0	-0.38	2	2
PGK/cGMP/p38 alpha	0.005	0.12	0.17	3	-0.43	17	20
apoptosis	-0.034	0.093	-10000	0	-0.38	21	21
RAL/GTP	0.036	0.009	-10000	0	-10000	0	0
LYN	0.025	0.009	-10000	0	-10000	0	0
DUSP1	0.017	0.064	-10000	0	-0.38	10	10
PAK1	0.027	0.005	-10000	0	-10000	0	0
SRC	0.024	0.01	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.06	0.028	-10000	0	-10000	0	0
TRAF6	0.027	0.005	-10000	0	-10000	0	0
RAC1	0.026	0.008	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
mol:cGMP	0	0	-10000	0	-10000	0	0
CCM2	0.026	0.007	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0.033	0.013	-10000	0	-10000	0	0
MAPK11	0.014	0.12	0.26	18	-0.44	13	31
BLK	-0.041	0.15	-10000	0	-0.38	66	66
HCK	0.024	0.01	-10000	0	-10000	0	0
MAP2K3	0.026	0.008	-10000	0	-10000	0	0
DUSP16	0.026	0.007	-10000	0	-10000	0	0
DUSP10	0.026	0.027	-10000	0	-0.35	2	2
TRAF6/MEKK3	0.034	0.008	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.01	0.13	0.21	24	-0.44	20	44
positive regulation of innate immune response	0.014	0.15	0.26	21	-0.52	15	36
LCK	0.017	0.062	-10000	0	-0.35	11	11
p38alpha-beta/MKP7	0.024	0.14	0.27	19	-0.49	14	33
p38alpha-beta/MKP5	0.021	0.14	0.28	17	-0.51	14	31
PGK/cGMP	0.016	0.031	-10000	0	-0.26	5	5
PAK2	0.026	0.007	-10000	0	-10000	0	0
p38alpha-beta/MKP1	0.02	0.15	0.27	18	-0.47	18	36
CDC42	0.026	0.007	-10000	0	-10000	0	0
RALB	0.028	0.003	-10000	0	-10000	0	0
RALA	0.027	0.006	-10000	0	-10000	0	0
PAK3	-0.033	0.14	-10000	0	-0.38	61	61

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.099	0.18	-10000	0	-0.66	4	4
CRP	-0.12	0.19	-10000	0	-0.64	12	12
cell cycle arrest	-0.13	0.2	-10000	0	-0.65	13	13
TIMP1	-0.094	0.17	-10000	0	-0.61	8	8
IL6ST	0.013	0.04	-10000	0	-0.39	3	3
Rac1/GDP	-0.047	0.098	-10000	0	-0.35	10	10
AP1	0.022	0.1	-10000	0	-0.47	6	6
GAB2	0.027	0.006	-10000	0	-10000	0	0
TNFSF11	-0.17	0.21	-10000	0	-0.62	27	27
HSP90B1	-0.003	0.099	-10000	0	-0.64	8	8
GAB1	0.027	0.006	-10000	0	-10000	0	0
MAPK14	-0.021	0.084	-10000	0	-0.39	5	5
AKT1	0.027	0.049	-10000	0	-0.41	2	2
FOXO1	0.035	0.058	0.25	3	-0.38	2	5
MAP2K6	-0.034	0.085	-10000	0	-0.35	10	10
mol:GTP	-0.002	0.002	-10000	0	-10000	0	0
MAP2K4	-0.064	0.11	-10000	0	-0.39	8	8
MITF	-0.044	0.094	-10000	0	-0.34	20	20
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.027	0.005	-10000	0	-10000	0	0
A2M	-0.02	0.23	-10000	0	-1.1	17	17
CEBPB	0.025	0.014	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.009	0.081	-10000	0	-0.45	7	7
STAT3	-0.14	0.2	-10000	0	-0.69	12	12
STAT1	0.001	0.08	-10000	0	-0.76	4	4
CEBPD	-0.11	0.18	-10000	0	-0.7	6	6
PIK3CA	0.027	0.007	-10000	0	-10000	0	0
PI3K	0.038	0.015	-10000	0	-10000	0	0
JUN	0.027	0.004	-10000	0	-10000	0	0
PIAS3/MITF	-0.038	0.1	0.24	1	-0.35	15	16
MAPK11	-0.019	0.08	-10000	0	-0.4	4	4
STAT3 (dimer)/FOXO1	-0.084	0.16	-10000	0	-0.57	4	4
GRB2/SOS1/GAB family	0.028	0.094	-10000	0	-0.33	4	4
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.017	0.083	-10000	0	-0.3	17	17
GRB2	0.028	0.005	-10000	0	-10000	0	0
JAK2	0.024	0.01	-10000	0	-10000	0	0
LBP	-0.095	0.19	0.41	1	-0.54	14	15
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
JAK1	0.023	0.014	-10000	0	-10000	0	0
MYC	-0.088	0.2	-10000	0	-0.8	5	5
FGG	-0.18	0.3	-10000	0	-0.94	46	46
macrophage differentiation	-0.13	0.2	-10000	0	-0.65	13	13
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0.016	0.099	-10000	0	-0.26	13	13
JUNB	-0.12	0.17	-10000	0	-0.62	6	6
FOS	0.006	0.091	-10000	0	-0.38	21	21
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.042	0.096	-10000	0	-0.33	20	20
STAT1/PIAS1	-0.048	0.11	-10000	0	-0.33	11	11
GRB2/SOS1/GAB family/SHP2/PI3K	0.029	0.053	-10000	0	-0.4	3	3
STAT3 (dimer)	-0.14	0.2	-10000	0	-0.69	12	12
PRKCD	-0.077	0.14	0.32	2	-0.45	8	10
IL6R	0.011	0.07	-10000	0	-0.39	12	12
SOCS3	-0.005	0.085	-10000	0	-10000	0	0
gp130 (dimer)/JAK1/JAK1/LMO4	0.031	0.05	-10000	0	-0.23	6	6
Rac1/GTP	-0.054	0.1	-10000	0	-0.37	10	10
HCK	0.024	0.01	-10000	0	-10000	0	0
MAPKKK cascade	0.018	0.088	-10000	0	-0.5	7	7
bone resorption	-0.17	0.2	-10000	0	-0.58	28	28
IRF1	-0.12	0.17	-10000	0	-0.64	6	6
mol:GDP	-0.044	0.09	-10000	0	-0.33	16	16
SOS1	0.028	0.003	-10000	0	-10000	0	0
VAV1	-0.044	0.09	-10000	0	-0.33	15	15
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.005	0.099	-10000	0	-0.5	6	6
PTPN11	0.001	0.096	-10000	0	-0.77	6	6
IL6/IL6RA	-0.013	0.11	-10000	0	-0.28	55	55
gp130 (dimer)/TYK2/TYK2/LMO4	0.04	0.04	-10000	0	-0.23	6	6
gp130 (dimer)/JAK2/JAK2/LMO4	0.037	0.041	-10000	0	-0.23	6	6
IL6	-0.031	0.13	-10000	0	-0.38	49	49
PIAS3	0.027	0.006	-10000	0	-10000	0	0
PTPRE	0.03	0.029	-10000	0	-0.35	2	2
PIAS1	0.027	0.005	-10000	0	-10000	0	0
RAC1	0.025	0.007	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.027	0.09	-10000	0	-0.28	28	28
LMO4	0.014	0.039	-10000	0	-0.37	3	3
STAT3 (dimer)/PIAS3	-0.13	0.19	-10000	0	-0.65	12	12
MCL1	0.033	0.063	-10000	0	-10000	0	0

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	0.017	0.038	-10000	0	-0.22	9	9
epithelial cell differentiation	0.047	0.041	-10000	0	-0.19	9	9
CYFIP2	0.02	0.053	-10000	0	-0.38	7	7
ENAH	-0.007	0.053	0.23	5	-0.24	1	6
EGFR	0.017	0.057	-10000	0	-0.38	8	8
EPHA2	0.021	0.047	-10000	0	-0.36	6	6
MYO6	-0.006	0.043	0.18	13	-10000	0	13
CTNNB1	0.027	0.006	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.046	0.04	-10000	0	-0.22	7	7
AQP5	-0.1	0.18	-10000	0	-0.42	89	89
CTNND1	0.027	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.007	0.042	0.18	12	-10000	0	12
regulation of calcium-dependent cell-cell adhesion	-0.009	0.046	0.18	12	-0.34	1	13
EGF	-0.016	0.12	-10000	0	-0.36	44	44
NCKAP1	0.028	0.004	-10000	0	-10000	0	0
AQP3	-0.008	0.088	-10000	0	-0.42	13	13
cortical microtubule organization	0.047	0.041	-10000	0	-0.19	9	9
GO:0000145	-0.008	0.039	0.16	11	-10000	0	11
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.052	0.043	-10000	0	-0.19	9	9
MLLT4	0.026	0.007	-10000	0	-10000	0	0
ARF6/GDP	-0.02	0.031	-10000	0	-0.33	1	1
ARF6	0.027	0.006	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.06	0.039	-10000	0	-0.19	6	6
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.004	0.04	0.18	9	-0.33	1	10
PVRL2	0.027	0.006	-10000	0	-10000	0	0
ZYX	-0.007	0.043	0.18	13	-10000	0	13
ARF6/GTP	0.064	0.042	-10000	0	-0.2	1	1
CDH1	0.018	0.06	-10000	0	-0.38	9	9
EGFR/EGFR/EGF/EGF	0.012	0.078	-10000	0	-0.34	2	2
RhoA/GDP	0.048	0.041	-10000	0	-0.19	6	6
actin cytoskeleton organization	-0.007	0.04	0.16	13	-10000	0	13
IGF-1R heterotetramer	0.025	0.028	-10000	0	-0.37	2	2
GIT1	0.028	0.004	-10000	0	-10000	0	0
IGF1R	0.025	0.028	-10000	0	-0.37	2	2
IGF1	-0.022	0.13	-10000	0	-0.37	51	51
DIAPH1	0.013	0.15	-10000	0	-0.53	19	19
Wnt receptor signaling pathway	-0.047	0.041	0.19	9	-10000	0	9
RHOA	0.027	0.006	-10000	0	-10000	0	0
RhoA/GTP	-0.021	0.03	-10000	0	-0.31	1	1
CTNNA1	0.027	0.006	-10000	0	-10000	0	0
VCL	-0.007	0.041	0.17	13	-10000	0	13
EFNA1	0.026	0.019	-10000	0	-0.35	1	1
LPP	-0.011	0.047	0.17	9	-0.4	2	11
Ephrin A1/EPHA2	0.037	0.048	-10000	0	-0.35	1	1
SEC6/SEC8	-0.016	0.024	-10000	0	-10000	0	0
MGAT3	-0.009	0.047	0.18	12	-0.34	1	13
HGF/MET	0.023	0.07	-10000	0	-0.34	2	2
HGF	0.014	0.07	-10000	0	-0.37	13	13
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.017	0.038	-10000	0	-0.22	9	9
actin cable formation	0.019	0.081	0.26	19	-0.34	1	20
KIAA1543	-0.007	0.041	0.17	13	-10000	0	13
KIFC3	-0.009	0.039	0.18	9	-10000	0	9
NCK1	0.027	0.005	-10000	0	-10000	0	0
EXOC3	0.025	0.009	-10000	0	-10000	0	0
ACTN1	-0.008	0.046	0.18	12	-0.34	1	13
NCK1/GIT1	0.04	0.009	-10000	0	-10000	0	0
mol:GDP	0.047	0.041	-10000	0	-0.19	9	9
EXOC4	0.027	0.006	-10000	0	-10000	0	0
STX4	-0.008	0.041	0.18	11	-10000	0	11
PIP5K1C	-0.008	0.042	0.18	12	-10000	0	12
LIMA1	0.027	0.005	-10000	0	-10000	0	0
ABI1	0.027	0.006	-10000	0	-10000	0	0
ROCK1	0	0.069	0.29	9	-0.28	1	10
adherens junction assembly	-0.012	0.099	0.27	3	-0.66	6	9
IGF-1R heterotetramer/IGF1	0.014	0.082	-10000	0	-0.33	3	3
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.038	0.013	-10000	0	-10000	0	0
MET	0.005	0.088	-10000	0	-0.36	23	23
PLEKHA7	-0.007	0.043	0.18	13	-10000	0	13
mol:GTP	0.057	0.038	-10000	0	-0.19	6	6
establishment of epithelial cell apical/basal polarity	0.013	0.083	0.32	12	-10000	0	12
cortical actin cytoskeleton stabilization	0.017	0.038	-10000	0	-0.22	9	9
regulation of cell-cell adhesion	-0.007	0.04	0.16	13	-10000	0	13
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.017	0.038	-10000	0	-0.22	9	9

×

Angiopoietin receptor Tie2-mediated signaling

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
AKT1	0.032	0.14	-10000	0	-0.78	6	6
NCK1/PAK1/Dok-R	-0.015	0.055	-10000	0	-0.4	5	5
NCK1/Dok-R	0.047	0.12	-10000	0	-0.81	6	6
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
mol:beta2-estradiol	-0.005	0.022	0.24	3	-10000	0	3
RELA	0.027	0.005	-10000	0	-10000	0	0
SHC1	0.028	0.006	-10000	0	-10000	0	0
Rac/GDP	0.019	0.006	-10000	0	-10000	0	0
F2	-0.054	0.13	0.26	3	-0.36	60	63
TNIP2	0.026	0.007	-10000	0	-10000	0	0
NF kappa B/RelA	0.063	0.12	-10000	0	-0.81	6	6
FN1	-0.01	0.11	-10000	0	-0.35	41	41
PLD2	0.019	0.12	-10000	0	-0.86	6	6
PTPN11	0.028	0.004	-10000	0	-10000	0	0
GRB14	-0.037	0.14	-10000	0	-0.36	68	68
ELK1	0.03	0.11	-10000	0	-0.81	6	6
GRB7	0.019	0.044	-10000	0	-0.37	5	5
PAK1	0.027	0.005	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	0.04	0.14	-10000	0	-0.83	6	6
CDKN1A	0.027	0.14	0.35	1	-0.64	6	7
ITGA5	0.021	0.049	-10000	0	-0.35	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	0.045	0.12	-10000	0	-0.81	6	6
CRK	0.026	0.008	-10000	0	-10000	0	0
mol:NO	0.036	0.12	0.36	6	-0.59	6	12
PLG	0.015	0.12	-10000	0	-0.87	6	6
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.029	0.12	-10000	0	-0.75	6	6
GRB2	0.027	0.005	-10000	0	-10000	0	0
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
ANGPT2	-0.018	0.17	0.34	1	-0.56	13	14
BMX	0.003	0.13	-10000	0	-0.92	6	6
ANGPT1	0.023	0.11	0.31	1	-1.1	3	4
tube development	0.015	0.14	0.35	2	-0.65	6	8
ANGPT4	0.016	0.043	-10000	0	-0.36	5	5
response to hypoxia	0.001	0.01	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	0.016	0.14	-10000	0	-0.93	6	6
alpha5/beta1 Integrin	0.033	0.043	-10000	0	-0.28	7	7
FGF2	0.009	0.084	-10000	0	-0.38	18	18
STAT5A (dimer)	0.027	0.16	-10000	0	-0.76	6	6
mol:L-citrulline	0.036	0.12	0.36	6	-0.59	6	12
AGTR1	-0.077	0.18	-10000	0	-0.38	102	102
MAPK14	0.021	0.14	-10000	0	-0.93	6	6
Tie2/SHP2	0.027	0.11	-10000	0	-0.93	3	3
TEK	0.026	0.1	-10000	0	-1	3	3
RPS6KB1	0.033	0.13	-10000	0	-0.76	6	6
Angiotensin II/AT1	-0.052	0.12	-10000	0	-0.26	102	102
Tie2/Ang1/GRB2	0.042	0.12	-10000	0	-0.88	6	6
MAPK3	0.018	0.11	-10000	0	-0.82	6	6
MAPK1	0.017	0.11	-10000	0	-0.82	6	6
Tie2/Ang1/GRB7	0.031	0.13	-10000	0	-0.91	6	6
NFKB1	0.027	0.005	-10000	0	-10000	0	0
MAPK8	0.019	0.12	-10000	0	-0.87	6	6
PI3K	0.025	0.14	-10000	0	-0.88	6	6
FES	0.025	0.14	-10000	0	-0.97	6	6
Crk/Dok-R	0.047	0.12	-10000	0	-0.81	6	6
Tie2/Ang1/ABIN2	0.042	0.12	-10000	0	-0.88	6	6
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.035	0.13	0.36	2	-0.7	6	8
STAT5A	0.028	0.004	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.048	0.15	0.4	5	-0.8	5	10
Tie2/Ang2	0.002	0.15	-10000	0	-0.86	6	6
Tie2/Ang1	0.025	0.12	-10000	0	-0.91	6	6
FOXO1	0.038	0.14	0.4	4	-0.74	5	9
ELF1	0.032	0.018	-10000	0	-10000	0	0
ELF2	0.023	0.12	-10000	0	-0.87	6	6
mol:Choline	0.02	0.11	-10000	0	-0.84	6	6
cell migration	-0.006	0.04	-10000	0	-0.23	5	5
FYN	0.013	0.15	-10000	0	-0.73	6	6
DOK2	0.023	0.03	-10000	0	-0.38	2	2
negative regulation of cell cycle	0.028	0.13	0.34	2	-0.58	6	8
ETS1	0.031	0.026	-10000	0	-0.25	3	3
PXN	0.057	0.14	0.36	19	-0.67	5	24
ITGB1	0.026	0.02	-10000	0	-0.35	1	1
NOS3	0.034	0.13	0.38	5	-0.67	6	11
RAC1	0.026	0.008	-10000	0	-10000	0	0
TNF	0.014	0.084	-10000	0	-0.34	21	21
MAPKKK cascade	0.02	0.11	-10000	0	-0.84	6	6
RASA1	0.025	0.008	-10000	0	-10000	0	0
Tie2/Ang1/Shc	0.041	0.12	-10000	0	-0.86	6	6
NCK1	0.027	0.005	-10000	0	-10000	0	0
vasculogenesis	0.037	0.11	0.34	7	-0.53	6	13
mol:Phosphatidic acid	0.02	0.11	-10000	0	-0.84	6	6
mol:Angiotensin II	0	0.005	-10000	0	-10000	0	0
mol:NADP	0.036	0.12	0.36	6	-0.59	6	12
Rac1/GTP	0.033	0.12	-10000	0	-0.71	6	6
MMP2	0.018	0.12	-10000	0	-0.87	6	6

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.027	0.006	-9999	-10000	0	0
SPHK1	0.011	0.078	-9999	-0.35	18	18
GNAI2	0.027	0.005	-9999	-10000	0	0
mol:S1P	0.009	0.028	-9999	-0.24	1	1
GNAO1	-0.055	0.16	-9999	-0.38	82	82
mol:Sphinganine-1-P	0.002	0.051	-9999	-0.24	17	17
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.047	0.046	-9999	-10000	0	0
GNAI3	0.027	0.005	-9999	-10000	0	0
G12/G13	0.038	0.013	-9999	-10000	0	0
S1PR3	0.023	0.039	-9999	-0.37	4	4
S1PR2	0.026	0.019	-9999	-0.35	1	1
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	0.002	0.033	-9999	-0.2	4	4
S1PR5	0.017	0.062	-9999	-0.35	11	11
S1PR4	0.023	0.038	-9999	-0.35	4	4
GNAI1	0.02	0.054	-9999	-0.38	7	7
S1P/S1P5/G12	0.031	0.053	-9999	-0.26	3	3
S1P/S1P3/Gq	0.016	0.07	-9999	-0.3	15	15
S1P/S1P4/Gi	-0.033	0.12	-9999	-0.35	33	33
GNAQ	0.027	0.006	-9999	-10000	0	0
GNAZ	0.001	0.1	-9999	-0.38	26	26
GNA14	0.02	0.053	-9999	-0.38	7	7
GNA15	0.022	0.042	-9999	-0.35	5	5
GNA12	0.026	0.008	-9999	-10000	0	0
GNA13	0.027	0.005	-9999	-10000	0	0
GNA11	0.026	0.007	-9999	-10000	0	0
ABCC1	0.027	0.005	-9999	-10000	0	0

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.008	0.094	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0.001	-10000	0	-10000	0	0
CRKL	0.027	0.006	-10000	0	-10000	0	0
STAT1 (dimer)/Cbp/p300	0.01	0.097	0.29	4	-0.28	8	12
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.026	0.047	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.023	0.064	-10000	0	-0.23	9	9
CaM/Ca2+	0.01	0.091	-10000	0	-10000	0	0
RAP1A	0.027	0.005	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	-0.011	0.089	-10000	0	-0.3	8	8
AKT1	-0.006	0.088	0.3	6	-10000	0	6
MAP2K1	-0.027	0.075	0.28	3	-10000	0	3
MAP3K11	-0.017	0.078	0.28	1	-10000	0	1
IFNGR1	0.016	0.025	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.044	0.13	-10000	0	-0.34	36	36
Rap1/GTP	-0.014	0.063	-10000	0	-10000	0	0
CRKL/C3G	0.039	0.011	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.01	0.1	-10000	0	-10000	0	0
CEBPB	0.01	0.11	0.31	3	-0.52	5	8
STAT3	0.028	0.004	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.002	0.15	-10000	0	-0.66	12	12
STAT1	-0.021	0.086	0.22	2	-0.3	8	10
CALM1	0.027	0.005	-10000	0	-10000	0	0
IFN-gamma (dimer)	-0.066	0.16	-10000	0	-0.35	101	101
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
STAT1 (dimer)/PIAS1	-0.005	0.093	0.28	4	-0.29	8	12
CEBPB/PTGES2/Cbp/p300	0.011	0.073	-10000	0	-0.37	3	3
mol:Ca2+	0.006	0.091	-10000	0	-10000	0	0
MAPK3	-0.015	0.12	-10000	0	-0.68	8	8
STAT1 (dimer)	-0.025	0.088	-10000	0	-0.36	4	4
MAPK1	-0.027	0.14	-10000	0	-0.67	15	15
JAK2	0.013	0.025	-10000	0	-10000	0	0
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
JAK1	0.016	0.025	-10000	0	-10000	0	0
CAMK2D	0.027	0.005	-10000	0	-10000	0	0
DAPK1	0.013	0.096	0.28	5	-0.44	6	11
SMAD7	-0.001	0.049	0.15	12	-10000	0	12
CBL/CRKL/C3G	0.006	0.088	0.28	3	-10000	0	3
PI3K	0.007	0.087	-10000	0	-10000	0	0
IFNG	-0.066	0.16	-10000	0	-0.35	101	101
apoptosis	0.006	0.095	0.26	4	-0.42	9	13
CAMK2G	0.027	0.007	-10000	0	-10000	0	0
STAT3 (dimer)	0.027	0.004	-10000	0	-10000	0	0
CAMK2A	0.004	0.092	-10000	0	-0.36	24	24
CAMK2B	-0.047	0.16	-10000	0	-0.38	73	73
FRAP1	-0.015	0.081	0.29	6	-10000	0	6
PRKCD	-0.013	0.089	0.28	6	-10000	0	6
RAP1B	0.027	0.007	-10000	0	-10000	0	0
negative regulation of cell growth	-0.023	0.064	-10000	0	-0.23	9	9
PTPN2	0.026	0.007	-10000	0	-10000	0	0
EP300	0.027	0.005	-10000	0	-10000	0	0
IRF1	-0.014	0.075	0.27	5	-10000	0	5
STAT1 (dimer)/PIASy	-0.006	0.094	0.28	4	-0.29	8	12
SOCS1	-0.005	0.18	-10000	0	-1	12	12
mol:GDP	0.004	0.083	0.26	3	-10000	0	3
CASP1	-0.003	0.055	0.15	11	-0.22	7	18
PTGES2	0.027	0.006	-10000	0	-10000	0	0
IRF9	0.018	0.047	0.16	13	-10000	0	13
mol:PI-3-4-5-P3	-0.004	0.077	-10000	0	-10000	0	0
RAP1/GDP	0	0.073	-10000	0	-10000	0	0
CBL	-0.019	0.077	0.2	4	-10000	0	4
MAP3K1	-0.016	0.077	0.28	1	-10000	0	1
PIAS1	0.027	0.005	-10000	0	-10000	0	0
PIAS4	0.026	0.007	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.023	0.064	-10000	0	-0.23	9	9
PTPN11	-0.013	0.087	0.28	5	-10000	0	5
CREBBP	0.027	0.007	-10000	0	-10000	0	0
RAPGEF1	0.027	0.005	-10000	0	-10000	0	0

×

IL2 signaling events mediated by PI3K

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
BCL2L1	0.03	0.072	-10000	0	-10000	0	0
UGCG	0.008	0.095	-10000	0	-0.61	9	9
AKT1/mTOR/p70S6K/Hsp90/TERT	0.003	0.11	0.24	1	-0.44	12	13
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.01	0.094	-10000	0	-0.6	9	9
mol:DAG	-0.004	0.12	-10000	0	-0.79	9	9
CaM/Ca2+/Calcineurin A alpha-beta B1	0.026	0.1	-10000	0	-0.49	5	5
FRAP1	0.016	0.11	-10000	0	-0.55	6	6
FOXO3	0.02	0.096	-10000	0	-0.46	3	3
AKT1	0.019	0.1	-10000	0	-0.46	4	4
GAB2	0.027	0.006	-10000	0	-10000	0	0
SMPD1	0.001	0.12	-10000	0	-0.64	13	13
SGMS1	0.009	0.09	-10000	0	-0.57	9	9
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
mol:GDP	0.004	0.006	-10000	0	-10000	0	0
CALM1	0.027	0.005	-10000	0	-10000	0	0
cell proliferation	0.034	0.091	0.23	2	-0.38	8	10
EIF3A	0.027	0.006	-10000	0	-10000	0	0
PI3K	0.039	0.016	-10000	0	-10000	0	0
RPS6KB1	0.005	0.074	-10000	0	-0.88	2	2
mol:sphingomyelin	-0.004	0.12	-10000	0	-0.79	9	9
natural killer cell activation	0	0.001	-10000	0	-0.011	2	2
JAK3	0.012	0.078	-10000	0	-0.35	18	18
PIK3R1	0.027	0.008	-10000	0	-10000	0	0
JAK1	0.029	0.005	-10000	0	-10000	0	0
NFKB1	0.027	0.005	-10000	0	-10000	0	0
MYC	0.051	0.13	0.36	3	-0.9	2	5
MYB	-0.024	0.12	-10000	0	-0.52	2	2
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.022	0.079	-10000	0	-0.37	3	3
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.029	0.077	-10000	0	-0.8	2	2
mol:PI-3-4-5-P3	0.021	0.081	-10000	0	-0.35	4	4
Rac1/GDP	0.02	0.012	-10000	0	-10000	0	0
T cell proliferation	0.025	0.074	0.24	5	-0.33	3	8
SHC1	0.027	0.005	-10000	0	-10000	0	0
RAC1	0.026	0.008	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	-0.003	0.014	-10000	0	-0.033	76	76
PRKCZ	0.026	0.074	0.25	5	-0.34	3	8
NF kappa B1 p50/RelA	0.038	0.11	-10000	0	-0.5	5	5
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.019	0.047	-10000	0	-0.3	1	1
HSP90AA1	0.025	0.027	-10000	0	-0.35	2	2
RELA	0.027	0.005	-10000	0	-10000	0	0
IL2RA	-0.004	0.1	-10000	0	-0.35	33	33
IL2RB	0.028	0.021	-10000	0	-0.39	1	1
TERT	-0.077	0.17	-10000	0	-0.35	111	111
E2F1	-0.009	0.081	-10000	0	-0.41	3	3
SOS1	0.028	0.003	-10000	0	-10000	0	0
RPS6	0.025	0.009	-10000	0	-10000	0	0
mol:cAMP	0.001	0.007	0.016	75	-10000	0	75
PTPN11	0.028	0.005	-10000	0	-10000	0	0
IL2RG	0.02	0.059	-10000	0	-0.37	9	9
actin cytoskeleton organization	0.025	0.074	0.24	5	-0.33	3	8
GRB2	0.028	0.005	-10000	0	-10000	0	0
IL2	0.022	0.028	-10000	0	-0.35	2	2
PIK3CA	0.028	0.007	-10000	0	-10000	0	0
Rac1/GTP	0.044	0.024	-10000	0	-10000	0	0
LCK	0.019	0.062	-10000	0	-0.35	11	11
BCL2	0.014	0.12	-10000	0	-0.81	6	6

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	0.002	0.057	0.3	1	-10000	0	1
DAPP1	0.013	0.12	0.25	14	-0.36	14	28
Src family/SYK family/BLNK-LAT/BTK-ITK	0.002	0.14	0.27	1	-0.48	15	16
mol:DAG	0.023	0.086	0.2	40	-0.21	4	44
HRAS	0.028	0.009	-10000	0	-10000	0	0
RAP1A	0.029	0.008	-10000	0	-10000	0	0
ARF5/GDP	0.037	0.071	0.2	3	-0.3	6	9
PLCG2	0.019	0.055	-10000	0	-0.37	8	8
PLCG1	0.023	0.011	-10000	0	-10000	0	0
ARF5	0.027	0.005	-10000	0	-10000	0	0
mol:GTP	-0.001	0.05	0.17	4	-10000	0	4
ARF1/GTP	0.009	0.049	0.23	6	-10000	0	6
RHOA	0.027	0.006	-10000	0	-10000	0	0
YES1	0.026	0.007	-10000	0	-10000	0	0
RAP1A/GTP	0	0.052	0.15	40	-10000	0	40
ADAP1	-0.003	0.046	0.16	3	-10000	0	3
ARAP3	-0.001	0.05	0.16	4	-10000	0	4
INPPL1	0.026	0.02	-10000	0	-0.35	1	1
PREX1	0.023	0.011	-10000	0	-10000	0	0
ARHGEF6	0.023	0.041	-10000	0	-0.38	4	4
ARHGEF7	0.026	0.008	-10000	0	-10000	0	0
ARF1	0.027	0.005	-10000	0	-10000	0	0
NRAS	0.029	0.008	-10000	0	-10000	0	0
FYN	0.027	0.005	-10000	0	-10000	0	0
ARF6	0.027	0.006	-10000	0	-10000	0	0
FGR	0.027	0.006	-10000	0	-10000	0	0
mol:Ca2+	0.018	0.058	0.17	23	-10000	0	23
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.017	0.062	-10000	0	-0.37	10	10
ZAP70	0.008	0.085	-10000	0	-0.36	21	21
mol:IP3	0.016	0.067	0.19	22	-10000	0	22
LYN	0.025	0.009	-10000	0	-10000	0	0
ARF1/GDP	0.038	0.072	0.2	4	-0.3	6	10
RhoA/GDP	0.046	0.057	0.21	16	-10000	0	16
PDK1/Src/Hsp90	0.044	0.029	-10000	0	-0.21	2	2
BLNK	0.011	0.08	-10000	0	-0.38	16	16
actin cytoskeleton reorganization	0.043	0.078	0.24	27	-10000	0	27
SRC	0.024	0.01	-10000	0	-10000	0	0
PLEKHA2	-0.01	0.017	-10000	0	-0.2	3	3
RAC1	0.026	0.008	-10000	0	-10000	0	0
PTEN	0.022	0.016	-10000	0	-10000	0	0
HSP90AA1	0.025	0.027	-10000	0	-0.35	2	2
ARF6/GTP	-0.002	0.052	0.16	1	-10000	0	1
RhoA/GTP	-0.002	0.051	0.15	26	-10000	0	26
Src family/SYK family/BLNK-LAT	-0.004	0.099	-10000	0	-0.36	15	15
BLK	-0.041	0.15	-10000	0	-0.38	66	66
PDPK1	0.027	0.007	-10000	0	-10000	0	0
CYTH1	-0.002	0.05	0.16	4	-10000	0	4
HCK	0.024	0.01	-10000	0	-10000	0	0
CYTH3	-0.003	0.045	0.16	3	-10000	0	3
CYTH2	-0.002	0.049	0.16	5	-10000	0	5
KRAS	0.025	0.011	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.015	0.049	-10000	0	-0.38	3	3
SGK1	0.018	0.057	-10000	0	-0.36	5	5
INPP5D	0.025	0.034	-10000	0	-0.36	3	3
mol:GDP	0.026	0.071	0.19	6	-0.32	6	12
SOS1	0.028	0.003	-10000	0	-10000	0	0
SYK	0.026	0.021	-10000	0	-0.38	1	1
ARF6/GDP	0.033	0.056	0.21	16	-10000	0	16
mol:PI-3-4-5-P3	-0.003	0.046	-10000	0	-10000	0	0
ARAP3/RAP1A/GTP	0	0.052	0.16	40	-10000	0	40
VAV1	0.022	0.043	-10000	0	-0.36	5	5
mol:PI-3-4-P2	0.01	0.026	-10000	0	-0.25	4	4
RAS family/GTP/PI3K Class I	0.04	0.04	-10000	0	-10000	0	0
PLEKHA1	-0.01	0.017	-10000	0	-0.2	3	3
Rac1/GDP	0.033	0.07	0.19	3	-0.3	6	9
LAT	0.026	0.019	-10000	0	-0.35	1	1
Rac1/GTP	0.015	0.059	-10000	0	-0.41	3	3
ITK	-0.009	0.059	0.16	2	-10000	0	2
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.02	0.098	0.21	35	-0.28	6	41
LCK	0.017	0.062	-10000	0	-0.35	11	11
BTK	-0.008	0.056	0.16	4	-10000	0	4

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	-0.1	0.36	0.35	2	-1.2	40	42
PLK1	0.026	0.13	-10000	0	-1.4	1	1
CDKN1B	0.044	0.12	0.31	5	-0.36	6	11
FOXO3	0.04	0.11	-10000	0	-0.73	3	3
KAT2B	0.027	0.044	-10000	0	-0.38	4	4
FOXO1/SIRT1	-0.008	0.13	0.26	2	-0.39	36	38
CAT	0.035	0.12	0.43	1	-0.89	3	4
CTNNB1	0.027	0.006	-10000	0	-10000	0	0
AKT1	0.022	0.032	-10000	0	-10000	0	0
FOXO1	-0.021	0.14	0.33	2	-0.41	39	41
MAPK10	0.001	0.078	0.2	15	-0.19	46	61
mol:GTP	0.001	0	-10000	0	-10000	0	0
FOXO4	0.023	0.078	0.34	3	-0.36	1	4
response to oxidative stress	0.002	0.02	-10000	0	-0.13	1	1
FOXO3A/SIRT1	0.044	0.11	-10000	0	-0.55	5	5
XPO1	0.028	0.003	-10000	0	-10000	0	0
EP300	0.018	0.029	-10000	0	-10000	0	0
BCL2L11	0.029	0.062	-10000	0	-0.8	2	2
FOXO1/SKP2	-0.01	0.13	0.27	2	-0.39	36	38
mol:GDP	0.002	0.02	-10000	0	-0.13	1	1
RAN	0.028	0.005	-10000	0	-10000	0	0
GADD45A	0.043	0.12	-10000	0	-0.66	6	6
YWHAQ	0.028	0.004	-10000	0	-10000	0	0
FOXO1/14-3-3 family	0.019	0.13	0.24	1	-0.45	18	19
MST1	-0.001	0.11	-10000	0	-0.35	34	34
CSNK1D	0.027	0.005	-10000	0	-10000	0	0
CSNK1E	0.027	0.005	-10000	0	-10000	0	0
FOXO4/14-3-3 family	0.006	0.12	-10000	0	-0.45	16	16
YWHAB	0.022	0.011	-10000	0	-10000	0	0
MAPK8	0.026	0.042	0.2	19	-10000	0	19
MAPK9	0.027	0.043	0.2	21	-10000	0	21
YWHAG	0.026	0.007	-10000	0	-10000	0	0
YWHAE	0.026	0.008	-10000	0	-10000	0	0
YWHAZ	0.023	0.011	-10000	0	-10000	0	0
SIRT1	0.027	0.01	-10000	0	-10000	0	0
SOD2	0.034	0.12	0.37	1	-0.53	3	4
RBL2	0.023	0.17	-10000	0	-0.69	16	16
RAL/GDP	0.036	0.026	-10000	0	-10000	0	0
CHUK	0.03	0.018	-10000	0	-10000	0	0
Ran/GTP	0.023	0.004	-10000	0	-10000	0	0
CSNK1G2	0.026	0.007	-10000	0	-10000	0	0
RAL/GTP	0.039	0.024	-10000	0	-10000	0	0
CSNK1G1	0.027	0.005	-10000	0	-10000	0	0
FASLG	-0.003	0.2	-10000	0	-1.2	11	11
SKP2	0.023	0.028	-10000	0	-0.35	2	2
USP7	0.028	0.006	-10000	0	-10000	0	0
IKBKB	0.028	0.018	-10000	0	-10000	0	0
CCNB1	0.032	0.11	-10000	0	-0.94	1	1
FOXO1-3a-4/beta catenin	0.048	0.11	0.28	10	-0.39	1	11
proteasomal ubiquitin-dependent protein catabolic process	-0.01	0.13	0.27	2	-0.38	36	38
CSNK1A1	0.027	0.006	-10000	0	-10000	0	0
SGK1	0.028	0.034	-10000	0	-0.4	2	2
CSNK1G3	0.026	0.008	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.04	0.008	-10000	0	-10000	0	0
ZFAND5	0.024	0.073	0.43	2	-10000	0	2
SFN	0.015	0.067	-10000	0	-0.37	12	12
CDK2	0.015	0.038	-10000	0	-0.2	1	1
FOXO3A/14-3-3	0.014	0.11	-10000	0	-0.45	12	12
CREBBP	0.015	0.037	-10000	0	-0.19	1	1
FBXO32	0.057	0.16	0.44	4	-0.95	5	9
BCL6	0.046	0.098	-10000	0	-0.67	2	2
RALB	0.029	0.003	-10000	0	-10000	0	0
RALA	0.027	0.007	-10000	0	-10000	0	0
YWHAH	0.027	0.005	-10000	0	-10000	0	0

×

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

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.025	0.009	-10000	0	-10000	0	0
Caspase 8 (4 units)	0.04	0.055	-10000	0	-0.25	1	1
NEF	-0.003	0.029	-10000	0	-0.16	9	9
NFKBIA	0.028	0.013	-10000	0	-10000	0	0
BIRC3	0.018	0.05	-10000	0	-0.34	6	6
CYCS	0.019	0.055	0.19	23	-10000	0	23
RIPK1	0.026	0.007	-10000	0	-10000	0	0
CD247	0.018	0.06	-10000	0	-0.4	6	6
MAP2K7	0	0.17	0.28	1	-0.62	23	24
protein ubiquitination	0.021	0.085	0.22	13	-0.36	8	21
CRADD	0.028	0.004	-10000	0	-10000	0	0
DAXX	0.027	0.006	-10000	0	-10000	0	0
FAS	0.026	0.007	-10000	0	-10000	0	0
BID	0.014	0.048	0.18	6	-0.23	7	13
NF-kappa-B/RelA/I kappa B alpha	0.056	0.034	-10000	0	-0.2	5	5
TRADD	0.027	0.006	-10000	0	-10000	0	0
MAP3K5	0.027	0.005	-10000	0	-10000	0	0
CFLAR	0.028	0.003	-10000	0	-10000	0	0
FADD	0.026	0.007	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.056	0.035	-10000	0	-0.2	5	5
MAPK8	0.001	0.16	0.32	3	-0.57	23	26
APAF1	0.028	0.004	-10000	0	-10000	0	0
TRAF1	0.025	0.027	-10000	0	-0.35	2	2
TRAF2	0.027	0.006	-10000	0	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.021	0.05	0.19	6	-0.24	7	13
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.019	0.09	-10000	0	-0.44	10	10
CHUK	0.02	0.089	0.23	13	-0.39	8	21
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.069	0.032	-10000	0	-10000	0	0
TCRz/NEF	0.013	0.061	-10000	0	-0.25	20	20
TNF	0.01	0.08	-10000	0	-0.36	18	18
FASLG	0	0.09	-10000	0	-0.43	15	15
NFKB1	0.028	0.014	-10000	0	-10000	0	0
TNFR1A/BAG4/TNF-alpha	0.036	0.054	-10000	0	-0.21	16	16
CASP6	0.039	0.097	-10000	0	-0.47	6	6
CASP7	0.033	0.079	0.26	9	-0.45	2	11
RELA	0.028	0.014	-10000	0	-10000	0	0
CASP2	0.027	0.006	-10000	0	-10000	0	0
CASP3	0.022	0.085	0.25	9	-0.42	3	12
TNFRSF1A	0.027	0.006	-10000	0	-10000	0	0
TNFR1A/BAG4	0.036	0.015	-10000	0	-10000	0	0
CASP8	0.028	0.003	-10000	0	-10000	0	0
CASP9	0.027	0.006	-10000	0	-10000	0	0
MAP3K14	0.018	0.092	0.2	4	-0.4	11	15
APAF-1/Caspase 9	0.027	0.056	-10000	0	-0.28	1	1
BCL2	0	0.14	0.31	3	-0.52	23	26

×

Regulation of nuclear SMAD2/3 signaling

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.02	0.022	-10000	0	-10000	0	0
HSPA8	0.026	0.008	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	0.05	0.082	-10000	0	-0.26	10	10
AKT1	0.026	0.019	-10000	0	-10000	0	0
GSC	-0.061	0.25	-10000	0	-1.1	19	19
NKX2-5	0.001	0	-10000	0	-10000	0	0
muscle cell differentiation	-0.001	0.1	0.33	12	-10000	0	12
SMAD2-3/SMAD4/SP1	0.046	0.082	-10000	0	-10000	0	0
SMAD4	0.021	0.039	-10000	0	-10000	0	0
CBFB	0.027	0.006	-10000	0	-10000	0	0
SAP18	0.026	0.007	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.016	0.082	-10000	0	-0.21	39	39
SMAD3/SMAD4/VDR	0.068	0.056	-10000	0	-10000	0	0
MYC	0.019	0.031	-10000	0	-0.39	2	2
CDKN2B	-0.085	0.26	-10000	0	-0.92	21	21
AP1	0.03	0.061	-10000	0	-0.25	2	2
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.011	0.098	-10000	0	-0.44	9	9
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.004	0.084	-10000	0	-0.35	15	15
SP3	0.029	0.004	-10000	0	-10000	0	0
CREB1	0.028	0.004	-10000	0	-10000	0	0
FOXH1	-0.05	0.15	-10000	0	-0.36	74	74
SMAD3/SMAD4/GR	0.053	0.064	-10000	0	-0.25	5	5
GATA3	0.017	0.061	-10000	0	-0.35	10	10
SKI/SIN3/HDAC complex/NCoR1	0.018	0.069	-10000	0	-0.39	7	7
MEF2C/TIF2	-0.005	0.093	0.22	1	-0.36	4	5
endothelial cell migration	0.036	0.13	0.52	6	-10000	0	6
MAX	0.031	0.011	-10000	0	-10000	0	0
RBBP7	0.028	0.005	-10000	0	-10000	0	0
RBBP4	0.027	0.005	-10000	0	-10000	0	0
RUNX2	0.022	0.042	-10000	0	-0.35	5	5
RUNX3	0.025	0.027	-10000	0	-0.35	2	2
RUNX1	0.018	0.053	-10000	0	-0.35	8	8
CTBP1	0.026	0.007	-10000	0	-10000	0	0
NR3C1	0.025	0.047	-10000	0	-0.39	5	5
VDR	0.027	0.005	-10000	0	-10000	0	0
CDKN1A	0.008	0.094	-10000	0	-0.73	4	4
KAT2B	0.023	0.04	-10000	0	-0.38	4	4
SMAD2/SMAD2/SMAD4/FOXH1	-0.009	0.12	-10000	0	-0.27	29	29
DCP1A	0.027	0.005	-10000	0	-10000	0	0
SKI	0.027	0.007	-10000	0	-10000	0	0
SERPINE1	-0.037	0.13	-10000	0	-0.53	6	6
SMAD3/SMAD4/ATF2	0.051	0.049	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	0.048	0.057	-10000	0	-0.24	5	5
SAP30	0.026	0.007	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.039	0.043	-10000	0	-10000	0	0
JUN	0.017	0.056	-10000	0	-0.25	2	2
SMAD3/SMAD4/IRF7	0.049	0.059	-10000	0	-0.26	1	1
TFE3	0.018	0.029	-10000	0	-0.16	2	2
COL1A2	-0.023	0.11	-10000	0	-0.29	58	58
mesenchymal cell differentiation	-0.046	0.059	0.27	4	-10000	0	4
DLX1	-0.028	0.14	-10000	0	-0.38	56	56
TCF3	0.026	0.007	-10000	0	-10000	0	0
FOS	0.008	0.092	-10000	0	-0.39	21	21
SMAD3/SMAD4/Max	0.057	0.054	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.05	0.02	-10000	0	-10000	0	0
ZBTB17	0.026	0.009	-10000	0	-10000	0	0
LAMC1	0.015	0.042	-10000	0	-0.31	2	2
TGIF2/HDAC complex/SMAD3/SMAD4	0.048	0.047	-10000	0	-10000	0	0
IRF7	0.024	0.027	-10000	0	-0.35	1	1
ESR1	0.014	0.078	-10000	0	-0.38	15	15
HNF4A	0.013	0.06	-10000	0	-0.38	9	9
MEF2C	-0.006	0.099	0.2	3	-0.35	4	7
SMAD2-3/SMAD4	0.048	0.059	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.047	0.027	-10000	0	-10000	0	0
IGHV3OR16-13	0.011	0.026	-10000	0	-0.32	2	2
TGIF2/HDAC complex	0.024	0.01	-10000	0	-10000	0	0
CREBBP	0.019	0.02	-10000	0	-10000	0	0
SKIL	0.026	0.008	-10000	0	-10000	0	0
HDAC1	0.027	0.005	-10000	0	-10000	0	0
HDAC2	0.027	0.005	-10000	0	-10000	0	0
SNIP1	0.028	0.005	-10000	0	-10000	0	0
GCN5L2	0	0.008	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.048	0.057	-10000	0	-0.33	2	2
MSG1/HSC70	0.012	0.084	-10000	0	-0.25	39	39
SMAD2	0.018	0.034	-10000	0	-0.15	4	4
SMAD3	0.027	0.036	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.021	0.036	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	-0.016	0.062	-10000	0	-0.28	6	6
NCOR1	0.026	0.008	-10000	0	-10000	0	0
NCOA2	0.024	0.022	-10000	0	-0.38	1	1
NCOA1	0.028	0.003	-10000	0	-10000	0	0
MYOD/E2A	0.029	0.035	-10000	0	-0.25	6	6
SMAD2-3/SMAD4/SP1/MIZ-1	0.057	0.083	-10000	0	-10000	0	0
IFNB1	0.006	0.064	-10000	0	-0.42	7	7
SMAD3/SMAD4/MEF2C	0.016	0.11	0.24	1	-0.34	3	4
CITED1	-0.009	0.11	-10000	0	-0.36	39	39
SMAD2-3/SMAD4/ARC105	0.059	0.062	-10000	0	-0.26	1	1
RBL1	0.024	0.01	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.013	0.098	-10000	0	-0.54	8	8
RUNX1-3/PEBPB2	0.043	0.046	-10000	0	-0.22	9	9
SMAD7	0.024	0.07	-10000	0	-0.38	2	2
MYC/MIZ-1	0.028	0.028	-10000	0	-0.27	2	2
SMAD3/SMAD4	-0.006	0.083	0.26	10	-0.3	1	11
IL10	0.012	0.068	-10000	0	-0.34	7	7
PIASy/HDAC complex	0.024	0.017	-10000	0	-10000	0	0
PIAS3	0.026	0.007	-10000	0	-10000	0	0
CDK2	0.021	0.018	-10000	0	-10000	0	0
IL5	0.009	0.063	-10000	0	-0.32	5	5
CDK4	0.021	0.02	-10000	0	-10000	0	0
PIAS4	0.024	0.017	-10000	0	-10000	0	0
ATF3	0.022	0.045	-10000	0	-0.38	5	5
SMAD3/SMAD4/SP1	0.035	0.075	-10000	0	-10000	0	0
FOXG1	-0.009	0.061	-10000	0	-0.35	11	11
FOXO3	0.013	0.019	-10000	0	-10000	0	0
FOXO1	0.012	0.018	-10000	0	-10000	0	0
FOXO4	0.012	0.024	-10000	0	-0.27	1	1
heart looping	-0.006	0.098	0.2	4	-0.35	4	8
CEBPB	0.022	0.014	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	0.013	0.11	-10000	0	-0.25	40	40
MYOD1	0.014	0.045	-10000	0	-0.35	6	6
SMAD3/SMAD4/HNF4	0.039	0.063	-10000	0	-0.28	7	7
SMAD3/SMAD4/GATA3	0.044	0.071	-10000	0	-10000	0	0
SnoN/SIN3/HDAC complex/NCoR1	0.026	0.008	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.062	0.07	-10000	0	-0.31	2	2
SMAD3/SMAD4/SP1-3	0.049	0.076	-10000	0	-10000	0	0
MED15	0.026	0.02	-10000	0	-0.35	1	1
SP1	0.014	0.042	-10000	0	-10000	0	0
SIN3B	0.027	0.005	-10000	0	-10000	0	0
SIN3A	0.027	0.005	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.003	0.1	-10000	0	-0.26	19	19
ITGB5	0.01	0.049	0.22	1	-10000	0	1
TGIF/SIN3/HDAC complex/CtBP	0.023	0.055	-10000	0	-0.37	4	4
SMAD3/SMAD4/AR	0.018	0.11	-10000	0	-0.25	34	34
AR	-0.024	0.14	-10000	0	-0.38	51	51
negative regulation of cell growth	0.014	0.06	-10000	0	-0.28	4	4
SMAD3/SMAD4/MYOD	0.042	0.057	-10000	0	-0.28	1	1
E2F5	0.023	0.028	-10000	0	-0.35	2	2
E2F4	0.027	0.006	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.011	0.11	-10000	0	-0.27	10	10
SMAD2-3/SMAD4/FOXO1-3a-4	0.018	0.082	-10000	0	-0.4	11	11
TFDP1	0.026	0.008	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.049	0.07	-10000	0	-0.25	2	2
SMAD3/SMAD4/RUNX2	0.046	0.059	-10000	0	-0.28	4	4
TGIF2	0.024	0.01	-10000	0	-10000	0	0
TGIF1	0.027	0.006	-10000	0	-10000	0	0
ATF2	0.028	0.004	-10000	0	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.02	0.046	-9999	-0.35	6	6
PLK4	0.023	0.038	-9999	-0.35	4	4
regulation of centriole replication	0.006	0.039	-9999	-0.24	10	10

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.027	0.005	-10000	0	-10000	0	0
HDAC2	0.027	0.005	-10000	0	-10000	0	0
GNB1/GNG2	0.044	0.048	-10000	0	-0.23	11	11
forebrain development	-0.015	0.14	-10000	0	-0.57	14	14
GNAO1	-0.055	0.16	-10000	0	-0.38	82	82
SMO/beta Arrestin2	0.029	0.049	-10000	0	-0.26	10	10
SMO	0.016	0.064	-10000	0	-0.39	10	10
ARRB2	0.026	0.008	-10000	0	-10000	0	0
GLI3/SPOP	0.031	0.091	0.24	1	-0.53	4	5
mol:GTP	0	0.002	-10000	0	-10000	0	0
GSK3B	0.027	0.005	-10000	0	-10000	0	0
GNAI2	0.027	0.006	-10000	0	-10000	0	0
SIN3/HDAC complex	0.061	0.027	-10000	0	-10000	0	0
GNAI1	0.02	0.054	-10000	0	-0.38	7	7
XPO1	0.026	0.013	-10000	0	-10000	0	0
GLI1/Su(fu)	-0.008	0.13	-10000	0	-0.57	11	11
SAP30	0.026	0.007	-10000	0	-10000	0	0
mol:GDP	0.016	0.064	-10000	0	-0.38	10	10
MIM/GLI2A	0.019	0.038	-10000	0	-0.41	1	1
IFT88	0.026	0.007	-10000	0	-10000	0	0
GNAI3	0.027	0.005	-10000	0	-10000	0	0
GLI2	0.007	0.072	0.21	1	-0.27	14	15
GLI3	0.019	0.092	0.24	1	-0.46	6	7
CSNK1D	0.027	0.005	-10000	0	-10000	0	0
CSNK1E	0.027	0.005	-10000	0	-10000	0	0
SAP18	0.026	0.007	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.026	0.007	-10000	0	-10000	0	0
GNG2	0.027	0.019	-10000	0	-0.35	1	1
Gi family/GTP	-0.036	0.13	-10000	0	-0.38	32	32
SIN3B	0.027	0.005	-10000	0	-10000	0	0
SIN3A	0.027	0.005	-10000	0	-10000	0	0
GLI3/Su(fu)	0.026	0.088	0.23	1	-0.46	7	8
GLI2/Su(fu)	0.014	0.081	0.2	1	-0.35	7	8
FOXA2	-0.024	0.21	-10000	0	-0.93	20	20
neural tube patterning	-0.015	0.14	-10000	0	-0.57	14	14
SPOP	0.028	0.003	-10000	0	-10000	0	0
Su(fu)/PIAS1	0.028	0.044	-10000	0	-0.32	1	1
GNB1	0.026	0.007	-10000	0	-10000	0	0
CSNK1G2	0.026	0.007	-10000	0	-10000	0	0
CSNK1G3	0.026	0.008	-10000	0	-10000	0	0
MTSS1	0.019	0.038	-10000	0	-0.41	1	1
embryonic limb morphogenesis	-0.015	0.14	-10000	0	-0.57	14	14
SUFU	0.018	0.031	-10000	0	-0.34	1	1
LGALS3	0.025	0.029	-10000	0	-0.38	2	2
catabolic process	0.03	0.12	0.24	3	-0.45	12	15
GLI3A/CBP	0.021	0.057	-10000	0	-0.31	10	10
KIF3A	0.025	0.02	-10000	0	-0.35	1	1
GLI1	-0.016	0.14	-10000	0	-0.59	14	14
RAB23	0.013	0.071	-10000	0	-0.35	15	15
CSNK1A1	0.027	0.006	-10000	0	-10000	0	0
IFT172	0.028	0.003	-10000	0	-10000	0	0
RBBP7	0.027	0.005	-10000	0	-10000	0	0
Su(fu)/Galectin3	0.026	0.048	-10000	0	-0.32	1	1
GNAZ	0.001	0.1	-10000	0	-0.38	26	26
RBBP4	0.027	0.005	-10000	0	-10000	0	0
CSNK1G1	0.027	0.005	-10000	0	-10000	0	0
PIAS1	0.027	0.005	-10000	0	-10000	0	0
PRKACA	0.027	0.005	-10000	0	-10000	0	0
GLI2/SPOP	0.018	0.077	0.2	1	-0.31	8	9
STK36	0.026	0.013	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.031	0.12	-10000	0	-0.37	30	30
PTCH1	-0.014	0.14	0.41	1	-0.74	7	8
MIM/GLI1	-0.015	0.16	-10000	0	-0.58	15	15
CREBBP	0.021	0.057	-10000	0	-0.31	10	10
Su(fu)/SIN3/HDAC complex	0.017	0.088	-10000	0	-0.43	12	12

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.024	0.041	-10000	0	-0.26	3	3
BIRC5	0.009	0.083	-10000	0	-0.36	20	20
NFKBIA	0.003	0.034	0.25	2	-0.26	3	5
CPEB1	-0.08	0.18	-10000	0	-0.38	106	106
AKT1	0.002	0.029	-10000	0	-0.26	3	3
NDEL1	0.026	0.007	-10000	0	-10000	0	0
Aurora A/BRCA1	0.016	0.036	-10000	0	-0.22	4	4
NDEL1/TACC3	0.042	0.045	-10000	0	-0.3	2	2
GADD45A	0.028	0.004	-10000	0	-10000	0	0
GSK3B	0.026	0.007	-10000	0	-10000	0	0
PAK1/Aurora A	0.025	0.041	-10000	0	-0.26	3	3
MDM2	0.025	0.027	-10000	0	-0.35	2	2
JUB	0	0	-10000	0	-10000	0	0
TPX2	-0.001	0.056	-10000	0	-0.25	20	20
TP53	0.014	0.026	-10000	0	-0.2	1	1
DLG7	0.003	0.028	-10000	0	-0.25	3	3
AURKAIP1	0.026	0.007	-10000	0	-10000	0	0
ARHGEF7	0.026	0.008	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.045	0.047	-10000	0	-0.32	2	2
G2/M transition of mitotic cell cycle	0.016	0.035	-10000	0	-0.22	4	4
AURKA	0.008	0.036	-10000	0	-0.3	3	3
AURKB	0.009	0.022	-10000	0	-0.15	3	3
CDC25B	0.009	0.028	-10000	0	-0.24	3	3
G2/M transition checkpoint	0.003	0.028	-10000	0	-0.23	3	3
mRNA polyadenylation	-0.031	0.094	-10000	0	-0.21	79	79
Aurora A/CPEB	-0.031	0.094	-10000	0	-0.21	79	79
Aurora A/TACC1/TRAP/chTOG	0.055	0.049	-10000	0	-0.22	3	3
BRCA1	0.027	0.019	-10000	0	-0.35	1	1
centrosome duplication	0.025	0.041	-10000	0	-0.26	3	3
regulation of centrosome cycle	0.041	0.044	-10000	0	-0.29	2	2
spindle assembly	0.054	0.048	-10000	0	-0.21	3	3
TDRD7	0.027	0.005	-10000	0	-10000	0	0
Aurora A/RasGAP/Survivin	0.046	0.064	-10000	0	-0.25	6	6
CENPA	0.011	0.027	-10000	0	-0.21	2	2
Aurora A/PP2A	0.023	0.042	-10000	0	-0.26	3	3
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	0.012	0.036	-10000	0	-0.25	3	3
negative regulation of DNA binding	0.013	0.03	-10000	0	-0.2	1	1
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.038	0.013	-10000	0	-10000	0	0
RASA1	0.025	0.008	-10000	0	-10000	0	0
Ajuba/Aurora A	0.003	0.028	-10000	0	-0.23	3	3
mitotic prometaphase	0.003	0.019	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.008	0.036	-10000	0	-0.3	3	3
TACC1	0.025	0.009	-10000	0	-10000	0	0
TACC3	0.025	0.02	-10000	0	-0.35	1	1
Aurora A/Antizyme1	0.047	0.043	-10000	0	-0.22	3	3
Aurora A/RasGAP	0.023	0.04	-10000	0	-0.24	3	3
OAZ1	0.026	0.007	-10000	0	-10000	0	0
RAN	0.027	0.005	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	0.026	0.007	-10000	0	-10000	0	0
GIT1	0.028	0.004	-10000	0	-10000	0	0
GIT1/beta-PIX/PAK1	0.05	0.019	-10000	0	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.001	0.056	-10000	0	-0.25	20	20
PPP2R5D	0.026	0.007	-10000	0	-10000	0	0
Aurora A/TPX2	0.005	0.058	-10000	0	-0.3	8	8
PAK1	0.027	0.005	-10000	0	-10000	0	0
CKAP5	0.027	0.005	-10000	0	-10000	0	0

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.028	0.004	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	0.035	0.059	-9999	-0.21	20	20
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	0.008	0.026	-9999	-0.29	2	2
AURKB	0.018	0.056	-9999	-0.36	9	9
AURKC	0.014	0.068	-9999	-0.36	13	13

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	0.002	0.091	-10000	0	-0.36	18	18
KLHL20	0.026	0.064	0.18	12	-0.2	3	15
CYFIP2	0.02	0.053	-10000	0	-0.38	7	7
Rac1/GDP	0.034	0.084	0.25	14	-0.28	2	16
ENAH	0.004	0.089	-10000	0	-0.37	16	16
AP1M1	0.027	0.005	-10000	0	-10000	0	0
RAP1B	0.027	0.007	-10000	0	-10000	0	0
RAP1A	0.027	0.005	-10000	0	-10000	0	0
CTNNB1	0.027	0.006	-10000	0	-10000	0	0
CDC42/GTP	0.016	0.038	-10000	0	-0.22	1	1
ABI1/Sra1/Nap1	-0.01	0.029	-10000	0	-0.16	4	4
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.054	0.049	-10000	0	-0.2	10	10
RAPGEF1	0.017	0.096	0.23	7	-0.33	15	22
CTNND1	0.027	0.005	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.008	0.098	-10000	0	-0.36	20	20
CRK	0.016	0.092	-10000	0	-0.35	15	15
E-cadherin/gamma catenin/alpha catenin	0.042	0.045	-10000	0	-0.23	9	9
alphaE/beta7 Integrin	0.037	0.02	-10000	0	-0.27	1	1
IQGAP1	0.026	0.007	-10000	0	-10000	0	0
NCKAP1	0.028	0.004	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.048	0.018	-10000	0	-10000	0	0
DLG1	0.003	0.091	-10000	0	-0.36	18	18
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.001	0.024	-10000	0	-10000	0	0
MLLT4	0.026	0.007	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.043	0.042	-10000	0	-0.2	10	10
PI3K	0.004	0.031	-10000	0	-10000	0	0
ARF6	0.027	0.006	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
E-cadherin/gamma catenin	0.03	0.047	-10000	0	-0.27	9	9
TIAM1	0.017	0.062	-10000	0	-0.37	10	10
E-cadherin(dimer)/Ca2+	0.052	0.043	-10000	0	-0.19	9	9
AKT1	0.005	0.038	0.13	4	-10000	0	4
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
CDH1	0.018	0.06	-10000	0	-0.38	9	9
RhoA/GDP	0.041	0.087	0.24	19	-0.27	2	21
actin cytoskeleton organization	0.024	0.053	0.16	18	-0.15	1	19
CDC42/GDP	0.04	0.087	0.25	17	-0.27	3	20
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.013	0.035	-10000	0	-0.21	9	9
ITGB7	0.026	0.021	-10000	0	-0.38	1	1
RAC1	0.026	0.008	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.056	0.047	-10000	0	-0.2	9	9
E-cadherin/Ca2+/beta catenin/alpha catenin	0.039	0.038	-10000	0	-0.19	9	9
mol:GDP	0.028	0.095	0.26	16	-0.28	9	25
CDC42/GTP/IQGAP1	0.034	0.012	-10000	0	-10000	0	0
JUP	0.026	0.008	-10000	0	-10000	0	0
p120 catenin/RhoA/GDP	0.049	0.088	0.24	22	-0.27	2	24
RAC1/GTP/IQGAP1	0.033	0.013	-10000	0	-10000	0	0
PIP5K1C/AP1M1	0.039	0.011	-10000	0	-10000	0	0
RHOA	0.027	0.006	-10000	0	-10000	0	0
CDC42	0.026	0.007	-10000	0	-10000	0	0
CTNNA1	0.027	0.006	-10000	0	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.02	0.039	0.13	14	-0.14	1	15
NME1	0.028	0.003	-10000	0	-10000	0	0
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	0.003	0.091	-10000	0	-0.36	19	19
regulation of cell-cell adhesion	0.01	0.031	-10000	0	-0.19	1	1
WASF2	0.012	0.025	0.089	1	-10000	0	1
Rap1/GTP	0.036	0.064	0.28	3	-0.24	1	4
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.059	0.053	-10000	0	-0.2	7	7
CCND1	0.022	0.046	0.16	12	-0.17	1	13
VAV2	0.02	0.13	-10000	0	-0.53	10	10
RAP1/GDP	0.046	0.078	0.25	14	-0.25	1	15
adherens junction assembly	0.004	0.089	-10000	0	-0.35	19	19
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.027	0.006	-10000	0	-10000	0	0
PIP5K1C	0.026	0.007	-10000	0	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.052	0.054	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.004	0.048	-10000	0	-0.28	11	11
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	0.001	0.089	-10000	0	-0.36	18	18
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
Rac1/GTP	-0.004	0.066	-10000	0	-0.3	7	7
E-cadherin/beta catenin/alpha catenin	0.044	0.044	-10000	0	-0.22	9	9
ITGAE	0.026	0.008	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.008	0.1	-10000	0	-0.37	20	20

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.077	0.16	-10000	0	-0.53	9	9
RAD9A	0.027	0.006	-10000	0	-10000	0	0
AP1	0.019	0.07	-10000	0	-0.28	21	21
IFNAR2	0.014	0.022	-10000	0	-10000	0	0
AKT1	0.001	0.044	-10000	0	-0.3	3	3
ER alpha/Oestrogen	0.005	0.054	-10000	0	-0.27	15	15
NFX1/SIN3/HDAC complex	0.025	0.04	-10000	0	-0.28	3	3
EGF	-0.02	0.12	-10000	0	-0.36	44	44
SMG5	0.027	0.005	-10000	0	-10000	0	0
SMG6	0.026	0.007	-10000	0	-10000	0	0
SP3/HDAC2	0.02	0.033	-10000	0	-10000	0	0
TERT/c-Abl	-0.065	0.15	-10000	0	-0.52	7	7
SAP18	0.026	0.007	-10000	0	-10000	0	0
MRN complex	0.046	0.023	-10000	0	-10000	0	0
WT1	-0.078	0.16	-10000	0	-0.36	101	101
WRN	0.025	0.009	-10000	0	-10000	0	0
SP1	0.012	0.026	-10000	0	-10000	0	0
SP3	0.026	0.006	-10000	0	-10000	0	0
TERF2IP	0.027	0.006	-10000	0	-10000	0	0
Telomerase/Nucleolin	-0.048	0.16	-10000	0	-0.5	5	5
Mad/Max	0.034	0.015	-10000	0	-10000	0	0
TERT	-0.078	0.16	-10000	0	-0.54	9	9
CCND1	-0.061	0.15	0.44	1	-0.58	4	5
MAX	0.026	0.006	-10000	0	-10000	0	0
RBBP7	0.027	0.005	-10000	0	-10000	0	0
RBBP4	0.027	0.005	-10000	0	-10000	0	0
TERF2	0.023	0.022	-10000	0	-0.37	1	1
PTGES3	0.027	0.005	-10000	0	-10000	0	0
SIN3A	0.027	0.005	-10000	0	-10000	0	0
Telomerase/911	0.026	0.053	-10000	0	-0.28	1	1
CDKN1B	-0.038	0.092	-10000	0	-10000	0	0
RAD1	0.026	0.008	-10000	0	-10000	0	0
XRCC5	0.028	0.004	-10000	0	-10000	0	0
XRCC6	0.027	0.006	-10000	0	-10000	0	0
SAP30	0.026	0.007	-10000	0	-10000	0	0
TRF2/PARP2	0.037	0.02	-10000	0	-0.29	1	1
UBE3A	0.026	0.006	-10000	0	-10000	0	0
JUN	0.026	0.005	-10000	0	-10000	0	0
E6	-0.002	0.004	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.01	0.017	-10000	0	-10000	0	0
FOS	0.005	0.091	-10000	0	-0.39	21	21
IFN-gamma/IRF1	-0.031	0.12	-10000	0	-0.24	100	100
PARP2	0.028	0.004	-10000	0	-10000	0	0
BLM	0.014	0.069	-10000	0	-0.35	14	14
Telomerase	0.006	0.09	-10000	0	-0.41	8	8
IRF1	0.027	0.01	-10000	0	-10000	0	0
ESR1	0.011	0.077	-10000	0	-0.38	15	15
KU/TER	0.039	0.01	-10000	0	-10000	0	0
ATM/TRF2	0.037	0.023	-10000	0	-0.24	2	2
ubiquitin-dependent protein catabolic process	0.024	0.056	-10000	0	-0.33	4	4
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.024	0.057	-10000	0	-0.34	4	4
HDAC1	0.027	0.005	-10000	0	-10000	0	0
HDAC2	0.011	0.025	-10000	0	-10000	0	0
ATM	0.012	0.016	-10000	0	-0.2	1	1
SMAD3	0.014	0.006	-10000	0	-10000	0	0
ABL1	0.027	0.006	-10000	0	-10000	0	0
MXD1	0.026	0.005	-10000	0	-10000	0	0
MRE11A	0.027	0.005	-10000	0	-10000	0	0
HUS1	0.026	0.007	-10000	0	-10000	0	0
RPS6KB1	0.028	0.004	-10000	0	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.054	0.16	-10000	0	-0.56	5	5
NR2F2	0.03	0.01	-10000	0	-10000	0	0
MAPK3	-0.007	0.023	-10000	0	-0.24	2	2
MAPK1	-0.007	0.023	-10000	0	-0.24	2	2
TGFB1/TGF beta receptor Type II	0.027	0.007	-10000	0	-10000	0	0
NFKB1	0.027	0.005	-10000	0	-10000	0	0
HNRNPC	0.028	0.004	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.012	0.016	-10000	0	-0.2	1	1
NBN	0.025	0.01	-10000	0	-10000	0	0
EGFR	0.016	0.057	-10000	0	-0.39	8	8
mol:Oestrogen	-0.001	0.002	-10000	0	-10000	0	0
EGF/EGFR	-0.005	0.093	-10000	0	-0.26	48	48
MYC	0.019	0.031	-10000	0	-0.39	2	2
IL2	0.005	0.036	-10000	0	-0.35	2	2
KU	0.039	0.01	-10000	0	-10000	0	0
RAD50	0.026	0.007	-10000	0	-10000	0	0
HSP90AA1	0.025	0.027	-10000	0	-0.35	2	2
TGFB1	0.027	0.007	-10000	0	-10000	0	0
TRF2/BLM	0.027	0.053	-10000	0	-0.25	13	13
FRAP1	0	0	-10000	0	-10000	0	0
KU/TERT	-0.058	0.16	-10000	0	-0.52	7	7
SP1/HDAC2	0.018	0.037	-10000	0	-10000	0	0
PINX1	0.024	0.01	-10000	0	-10000	0	0
Telomerase/EST1A	-0.049	0.15	-10000	0	-0.5	5	5
Smad3/Myc	0.022	0.023	-10000	0	-0.23	2	2
911 complex	0.047	0.022	-10000	0	-10000	0	0
IFNG	-0.067	0.16	-10000	0	-0.35	101	101
Telomerase/PinX1	-0.048	0.15	-10000	0	-0.5	5	5
Telomerase/AKT1/mTOR/p70S6K	-0.012	0.094	-10000	0	-0.39	11	11
SIN3B	0.027	0.005	-10000	0	-10000	0	0
YWHAE	0.026	0.008	-10000	0	-10000	0	0
Telomerase/EST1B	-0.048	0.15	-10000	0	-0.5	5	5
response to DNA damage stimulus	0.002	0.02	-10000	0	-10000	0	0
MRN complex/TRF2/Rap1	0.063	0.037	-10000	0	-0.22	1	1
TRF2/WRN	0.034	0.022	-10000	0	-0.29	1	1
Telomerase/hnRNP C1/C2	-0.047	0.15	-10000	0	-0.5	5	5
E2F1	0.006	0.058	-10000	0	-0.36	9	9
ZNFX1	0.022	0.011	-10000	0	-10000	0	0
PIF1	0.018	0.059	-10000	0	-0.35	10	10
NCL	0.028	0.003	-10000	0	-10000	0	0
DKC1	0.027	0.006	-10000	0	-10000	0	0
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0.028	0.062	-10000	0	-0.2	26	26
MAPK9	0.007	0.002	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.012	0.035	-10000	0	-0.24	9	9
GNB1/GNG2	0.035	0.016	-10000	0	-0.2	1	1
GNB1	0.026	0.007	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.007	0.002	-10000	0	-10000	0	0
Gs family/GTP	0.003	0.054	-10000	0	-0.2	27	27
EntrezGene:2778	0	0	-10000	0	-10000	0	0
vasopressin secretion	0	0	-10000	0	-10000	0	0
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
glutamate secretion	0.005	0.014	0.057	27	-10000	0	27
GNAL	-0.001	0.1	-10000	0	-0.38	27	27
GNG2	0.027	0.019	-10000	0	-0.35	1	1
CRH	0.01	0.055	-10000	0	-0.35	9	9
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.007	0.001	-10000	0	-10000	0	0
MAPK11	0.007	0.002	-10000	0	-10000	0	0

×

Thromboxane A2 receptor signaling

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
TGM2	0.017	0.05	-10000	0	-0.36	7	7
GNB1/GNG2	-0.032	0.039	-10000	0	-0.17	4	4
AKT1	-0.016	0.084	0.26	2	-0.3	10	12
EGF	-0.016	0.12	-10000	0	-0.36	44	44
mol:TXA2	0	0	-10000	0	-10000	0	0
FGR	0.008	0.049	0.25	1	-10000	0	1
mol:Ca2+	-0.025	0.089	0.28	2	-0.29	4	6
LYN	0.007	0.045	0.25	1	-10000	0	1
RhoA/GTP	-0.013	0.039	-10000	0	-10000	0	0
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.03	0.095	0.51	1	-0.31	2	3
GNG2	0.027	0.019	-10000	0	-0.35	1	1
ARRB2	0.026	0.007	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.012	0.14	-10000	0	-0.59	19	19
G beta5/gamma2	-0.034	0.054	-10000	0	-0.22	4	4
PRKCH	-0.028	0.095	0.29	2	-0.32	2	4
DNM1	0.016	0.064	-10000	0	-0.35	12	12
TXA2/TP beta/beta Arrestin3	-0.002	0.082	-10000	0	-0.53	9	9
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	0.007	0.09	-10000	0	-0.38	21	21
G12 family/GTP	-0.032	0.077	-10000	0	-0.28	2	2
ADRBK1	0.027	0.006	-10000	0	-10000	0	0
ADRBK2	0.027	0.006	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0.035	0.011	-10000	0	-10000	0	0
mol:GDP	0.017	0.088	0.35	13	-0.27	1	14
mol:NADP	0.023	0.038	-10000	0	-0.35	4	4
RAB11A	0.027	0.005	-10000	0	-10000	0	0
PRKG1	0.022	0.044	-10000	0	-0.37	5	5
mol:IP3	-0.031	0.1	0.38	1	-0.35	6	7
cell morphogenesis	0.034	0.01	-10000	0	-10000	0	0
PLCB2	-0.044	0.13	0.41	1	-0.46	6	7
mol:cGMP	0	0	-10000	0	-10000	0	0
BLK	-0.02	0.075	0.25	1	-0.27	6	7
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.005	0.044	0.25	1	-10000	0	1
RHOA	0.027	0.006	-10000	0	-10000	0	0
PTGIR	0.027	0.006	-10000	0	-10000	0	0
PRKCB1	-0.03	0.099	0.35	1	-0.33	4	5
GNAQ	0.027	0.006	-10000	0	-10000	0	0
mol:L-citrulline	0.023	0.038	-10000	0	-0.35	4	4
TXA2/TXA2-R family	-0.045	0.12	0.4	1	-0.45	4	5
LCK	0.004	0.055	0.25	1	-10000	0	1
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.02	0.053	-10000	0	-0.22	1	1
TXA2-R family/G12 family/GDP/G beta/gamma	0.013	0.081	-10000	0	-0.4	14	14
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.024	0.051	-10000	0	-10000	0	0
MAPK14	-0.018	0.073	0.25	5	-0.22	1	6
TGM2/GTP	-0.042	0.11	0.43	1	-0.4	6	7
MAPK11	-0.019	0.069	0.25	3	-0.22	1	4
ARHGEF1	-0.018	0.051	-10000	0	-0.18	1	1
GNAI2	0.027	0.005	-10000	0	-10000	0	0
JNK cascade	-0.034	0.1	0.38	1	-0.34	4	5
RAB11/GDP	0.027	0.005	-10000	0	-10000	0	0
ICAM1	-0.024	0.082	0.32	1	-0.28	5	6
cAMP biosynthetic process	-0.035	0.1	0.37	1	-0.34	4	5
Gq family/GTP/EBP50	0.013	0.039	0.24	3	-0.24	1	4
actin cytoskeleton reorganization	0.034	0.01	-10000	0	-10000	0	0
SRC	0.005	0.041	-10000	0	-10000	0	0
GNB5	0.027	0.005	-10000	0	-10000	0	0
GNB1	0.026	0.007	-10000	0	-10000	0	0
EGF/EGFR	0.011	0.085	0.21	20	-0.26	8	28
VCAM1	-0.025	0.082	0.34	1	-0.28	3	4
TP beta/Gq family/GDP/G beta5/gamma2	-0.012	0.14	-10000	0	-0.59	19	19
platelet activation	-0.023	0.093	0.31	4	-0.28	2	6
PGI2/IP	0.02	0.005	-10000	0	-10000	0	0
PRKACA	0.007	0.048	-10000	0	-0.21	19	19
Gq family/GDP/G beta5/gamma2	-0.009	0.13	0.2	1	-0.53	19	20
TXA2/TP beta/beta Arrestin2	-0.002	0.056	-10000	0	-0.33	7	7
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.002	0.04	-10000	0	-0.19	17	17
mol:DAG	-0.033	0.11	0.38	1	-0.37	4	5
EGFR	0.017	0.057	-10000	0	-0.38	8	8
TXA2/TP alpha	-0.045	0.13	0.42	1	-0.46	4	5
Gq family/GTP	-0.004	0.056	-10000	0	-0.2	27	27
YES1	0.008	0.049	0.25	1	-10000	0	1
GNAI2/GTP	0.015	0.044	-10000	0	-0.22	1	1
PGD2/DP	0.006	0.063	-10000	0	-0.27	21	21
SLC9A3R1	0.028	0.004	-10000	0	-10000	0	0
FYN	0.008	0.05	0.25	1	-10000	0	1
mol:NO	0.023	0.038	-10000	0	-0.35	4	4
GNA15	0.022	0.042	-10000	0	-0.35	5	5
PGK/cGMP	0.029	0.038	-10000	0	-0.21	9	9
RhoA/GDP	0.027	0.006	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0.033	0.058	-10000	0	-0.28	2	2
NOS3	0.023	0.038	-10000	0	-0.35	4	4
RAC1	0.026	0.008	-10000	0	-10000	0	0
PRKCA	-0.027	0.095	0.29	2	-0.31	3	5
PRKCB	-0.032	0.097	0.43	1	-0.37	4	5
PRKCE	-0.027	0.093	0.29	1	-0.31	2	3
PRKCD	-0.029	0.096	0.35	1	-0.34	2	3
PRKCG	-0.053	0.12	0.32	2	-0.36	8	10
muscle contraction	-0.044	0.12	0.45	1	-0.43	4	5
PRKCZ	-0.029	0.093	0.35	1	-0.32	2	3
ARR3	0.02	0.027	-10000	0	-0.35	2	2
TXA2/TP beta	0.026	0.054	-10000	0	-0.23	1	1
PRKCQ	-0.03	0.098	0.31	3	-0.34	3	6
MAPKKK cascade	-0.039	0.11	0.39	1	-0.42	4	5
SELE	-0.034	0.095	0.34	1	-0.31	3	4
TP beta/GNAI2/GDP/G beta/gamma	0.04	0.056	-10000	0	-0.23	1	1
ROCK1	0.027	0.006	-10000	0	-10000	0	0
GNA14	0.02	0.053	-10000	0	-0.38	7	7
chemotaxis	-0.05	0.13	0.42	1	-0.5	3	4
GNA12	0.026	0.008	-10000	0	-10000	0	0
GNA13	0.027	0.005	-10000	0	-10000	0	0
GNA11	0.026	0.007	-10000	0	-10000	0	0
Rac1/GTP	0.019	0.006	-10000	0	-10000	0	0

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.039	0.062	0.38	1	-10000	0	1
CRKL	0.028	0.057	0.29	6	-10000	0	6
mol:DAG	0.023	0.036	-10000	0	-10000	0	0
HRAS	0.014	0.071	0.29	12	-10000	0	12
MAPK8	0.032	0.062	0.19	32	-10000	0	32
RAP1A	0.028	0.056	0.3	5	-10000	0	5
GAB1	0.027	0.057	0.29	6	-10000	0	6
MAPK14	0.033	0.06	0.19	30	-10000	0	30
EPO	0.016	0.056	-10000	0	-0.35	9	9
PLCG1	0.024	0.037	-10000	0	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0.029	0.013	-10000	0	-10000	0	0
RAPGEF1	0.027	0.005	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.045	0.042	-10000	0	-0.19	9	9
GAB1/SHC/GRB2/SOS1	0.057	0.05	0.27	4	-10000	0	4
EPO/EPOR (dimer)	0.032	0.045	-10000	0	-0.24	9	9
IRS2	0.019	0.061	0.29	4	-0.32	1	5
STAT1	0.028	0.048	0.25	2	-10000	0	2
STAT5B	0.028	0.043	0.25	1	-10000	0	1
cell proliferation	0.018	0.079	0.19	60	-10000	0	60
GAB1/SHIP/PIK3R1/SHP2/SHC	0.04	0.043	-10000	0	-0.28	1	1
TEC	0.027	0.058	0.29	6	-10000	0	6
SOCS3	0.027	0.005	-10000	0	-10000	0	0
STAT1 (dimer)	0.028	0.048	0.24	2	-10000	0	2
JAK2	0.026	0.015	-10000	0	-10000	0	0
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.057	0.05	-10000	0	-10000	0	0
EPO/EPOR	0.032	0.045	-10000	0	-0.24	9	9
LYN	0.025	0.011	-10000	0	-10000	0	0
TEC/VAV2	0.036	0.054	0.28	4	-10000	0	4
elevation of cytosolic calcium ion concentration	0.029	0.013	-10000	0	-10000	0	0
SHC1	0.027	0.005	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	0.044	0.041	-10000	0	-0.2	6	6
mol:IP3	0.023	0.036	-10000	0	-10000	0	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.04	0.068	0.29	4	-0.45	1	5
SH2B3	0.029	0.012	-10000	0	-10000	0	0
NFKB1	0.034	0.063	0.19	33	-10000	0	33
EPO/EPOR (dimer)/JAK2/SOCS3	0.007	0.032	-10000	0	-0.22	5	5
PTPN6	0.027	0.053	0.3	1	-10000	0	1
TEC/VAV2/GRB2	0.047	0.056	0.28	5	-10000	0	5
EPOR	0.029	0.013	-10000	0	-10000	0	0
INPP5D	0.025	0.034	-10000	0	-0.36	3	3
mol:GDP	0.056	0.05	0.28	4	-10000	0	4
SOS1	0.028	0.003	-10000	0	-10000	0	0
PLCG2	0.019	0.055	-10000	0	-0.37	8	8
CRKL/CBL/C3G	0.049	0.054	0.28	6	-10000	0	6
VAV2	0.025	0.057	0.29	5	-10000	0	5
CBL	0.026	0.056	0.29	6	-10000	0	6
SHC/Grb2/SOS1	0.035	0.036	-10000	0	-10000	0	0
STAT5A	0.029	0.043	0.25	1	-10000	0	1
GRB2	0.027	0.005	-10000	0	-10000	0	0
STAT5 (dimer)	0.044	0.054	0.26	2	-10000	0	2
LYN/PLCgamma2	0.032	0.038	-10000	0	-0.25	6	6
PTPN11	0.028	0.004	-10000	0	-10000	0	0
BTK	0.021	0.069	0.29	6	-0.29	2	8
BCL2	0.036	0.1	-10000	0	-0.7	5	5

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.022	0.05	-10000	0	-0.4	5	5
PDGF/PDGFRA/CRKL	0.034	0.038	-10000	0	-0.26	5	5
positive regulation of JUN kinase activity	0.061	0.036	-10000	0	-0.2	5	5
CRKL	0.027	0.006	-10000	0	-10000	0	0
PDGF/PDGFRA/Caveolin-3	0.03	0.04	-10000	0	-0.27	6	6
AP1	-0.032	0.18	0.32	4	-0.72	22	26
mol:IP3	0.007	0.03	-10000	0	-0.28	3	3
PLCG1	0.007	0.03	-10000	0	-0.28	3	3
PDGF/PDGFRA/alphaV Integrin	0.033	0.038	-10000	0	-0.26	5	5
RAPGEF1	0.027	0.005	-10000	0	-10000	0	0
CRK	0.026	0.008	-10000	0	-10000	0	0
mol:Ca2+	0.007	0.03	-10000	0	-0.28	3	3
CAV3	0.021	0.019	-10000	0	-0.35	1	1
CAV1	0.024	0.033	-10000	0	-0.35	3	3
SHC/Grb2/SOS1	0.063	0.037	-10000	0	-0.2	5	5
PDGF/PDGFRA/Shf	0.021	0.076	-10000	0	-0.29	21	21
FOS	-0.042	0.16	0.31	1	-0.7	22	23
JUN	-0.016	0.02	-10000	0	-10000	0	0
oligodendrocyte development	0.033	0.038	-10000	0	-0.26	5	5
GRB2	0.027	0.005	-10000	0	-10000	0	0
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
mol:DAG	0.007	0.03	-10000	0	-0.28	3	3
PDGF/PDGFRA	0.022	0.05	-10000	0	-0.4	5	5
actin cytoskeleton reorganization	0.034	0.035	-10000	0	-0.27	4	4
SRF	0.01	0.01	-10000	0	-10000	0	0
SHC1	0.027	0.005	-10000	0	-10000	0	0
PI3K	0.047	0.031	-10000	0	-0.22	3	3
PDGF/PDGFRA/Crk/C3G	0.047	0.036	-10000	0	-0.22	5	5
JAK1	0.009	0.033	-10000	0	-0.27	5	5
ELK1/SRF	0	0.05	0.16	27	-0.27	1	28
SHB	0.026	0.007	-10000	0	-10000	0	0
SHF	0.009	0.084	-10000	0	-0.38	18	18
CSNK2A1	0.023	0.018	-10000	0	-10000	0	0
GO:0007205	0.001	0.03	-10000	0	-0.31	3	3
SOS1	0.028	0.003	-10000	0	-10000	0	0
Ras protein signal transduction	0.061	0.036	-10000	0	-0.2	5	5
PDGF/PDGFRA/SHB	0.034	0.035	-10000	0	-0.27	4	4
PDGF/PDGFRA/Caveolin-1	0.031	0.046	-10000	0	-0.27	8	8
ITGAV	0.026	0.007	-10000	0	-10000	0	0
ELK1	-0.008	0.029	-10000	0	-0.28	3	3
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
PDGF/PDGFRA/Crk	0.033	0.038	-10000	0	-0.26	5	5
JAK-STAT cascade	0.009	0.033	-10000	0	-0.27	5	5
cell proliferation	0.021	0.076	-10000	0	-0.29	21	21

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.028	0.004	-10000	0	-10000	0	0
mol:PIP3	0.007	0.02	-10000	0	-0.26	1	1
FRAP1	0.015	0.061	0.22	1	-0.42	5	6
AKT1	0.01	0.045	0.18	5	-0.22	1	6
INSR	0.027	0.006	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.029	0.009	-10000	0	-10000	0	0
mol:GTP	0.037	0.051	0.26	6	-10000	0	6
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0.013	0.02	-10000	0	-10000	0	0
TSC2	0.027	0.006	-10000	0	-10000	0	0
RHEB/GDP	0.02	0.025	-10000	0	-10000	0	0
TSC1	0.027	0.005	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.023	0.029	-10000	0	-0.2	6	6
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.028	0.03	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.027	0.006	-10000	0	-10000	0	0
RPS6KB1	0.031	0.063	0.26	11	-0.26	2	13
MAP3K5	0.005	0.036	0.19	7	-0.18	9	16
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
apoptosis	0.005	0.036	0.19	7	-0.18	9	16
mol:LY294002	0	0	-10000	0	-0.001	6	6
EIF4B	0.031	0.062	0.25	12	-10000	0	12
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.043	0.048	0.23	5	-10000	0	5
eIF4E/eIF4G1/eIF4A1	0.015	0.034	-10000	0	-0.25	5	5
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.036	0.029	-10000	0	-0.28	1	1
mTOR/RHEB/GTP/Raptor/GBL	0.017	0.044	0.2	13	-10000	0	13
FKBP1A	0.025	0.009	-10000	0	-10000	0	0
RHEB/GTP	0.039	0.043	0.23	5	-10000	0	5
mol:Amino Acids	0	0	-10000	0	-0.001	6	6
FKBP12/Rapamycin	0.019	0.007	-10000	0	-10000	0	0
PDPK1	0	0.038	0.16	17	-0.24	1	18
EIF4E	0.027	0.005	-10000	0	-10000	0	0
ASK1/PP5C	0.027	0.098	-10000	0	-0.5	12	12
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0	0.078	-10000	0	-0.29	18	18
TSC1/TSC2	0.043	0.058	0.28	8	-10000	0	8
tumor necrosis factor receptor activity	0	0	0.001	6	-10000	0	6
RPS6	0.025	0.009	-10000	0	-10000	0	0
PPP5C	0.027	0.006	-10000	0	-10000	0	0
EIF4G1	0.026	0.007	-10000	0	-10000	0	0
IRS1	0.006	0.028	-10000	0	-0.21	6	6
INS	0.018	0.005	-10000	0	-10000	0	0
PTEN	0.026	0.008	-10000	0	-10000	0	0
PDK2	0	0.04	0.16	17	-0.24	1	18
EIF4EBP1	-0.031	0.23	-10000	0	-1	22	22
PIK3CA	0.027	0.007	-10000	0	-10000	0	0
PPP2R5D	0.025	0.072	0.26	8	-0.38	5	13
peptide biosynthetic process	-0.008	0.022	0.18	5	-10000	0	5
RHEB	0.027	0.006	-10000	0	-10000	0	0
EIF4A1	0.026	0.008	-10000	0	-10000	0	0
mol:Rapamycin	0	0.001	0.003	30	-10000	0	30
EEF2	-0.008	0.022	0.18	5	-10000	0	5
eIF4E/4E-BP1	-0.016	0.22	-10000	0	-0.94	22	22

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.027	0.005	-10000	0	-10000	0	0
HDAC4	0.027	0.005	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.006	0.036	0.25	8	-0.13	1	9
CDKN1A	-0.009	0.03	-10000	0	-0.61	1	1
KAT2B	0.024	0.041	-10000	0	-0.38	4	4
BAX	0.027	0.006	-10000	0	-10000	0	0
FOXO3	-0.005	0.003	-10000	0	-10000	0	0
FOXO1	0.026	0.008	-10000	0	-10000	0	0
FOXO4	0.014	0.013	-10000	0	-0.23	1	1
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.027	0.006	-10000	0	-10000	0	0
TAT	-0.004	0.1	-10000	0	-0.38	29	29
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.016	0.04	-10000	0	-0.26	10	10
PPARGC1A	-0.005	0.11	-10000	0	-0.38	33	33
FHL2	0.024	0.041	-10000	0	-0.38	4	4
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.037	0.012	-10000	0	-10000	0	0
HIST2H4A	0.006	0.036	0.13	1	-0.25	8	9
SIRT1/FOXO3a	0.017	0.022	-10000	0	-0.19	1	1
SIRT1	0.025	0.01	0.2	1	-10000	0	1
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.05	0.017	-10000	0	-10000	0	0
SIRT1/Histone H1b	0.014	0.051	-10000	0	-0.21	10	10
apoptosis	-0.049	0.018	-10000	0	-10000	0	0
SIRT1/PGC1A	0.013	0.07	-10000	0	-0.22	33	33
p53/SIRT1	0.031	0.02	0.37	1	-10000	0	1
SIRT1/FOXO4	0.017	0.044	-10000	0	-0.2	5	5
FOXO1/FHL2/SIRT1	0.044	0.027	-10000	0	-0.21	2	2
HIST1H1E	0.01	0.028	-10000	0	-0.23	4	4
SIRT1/p300	0.037	0.012	-10000	0	-10000	0	0
muscle cell differentiation	-0.026	0.041	0.22	10	-0.22	2	12
TP53	0.023	0.011	0.2	1	-10000	0	1
KU70/SIRT1/BAX	0.049	0.019	-10000	0	-10000	0	0
CREBBP	0.026	0.007	-10000	0	-10000	0	0
MEF2D	0.027	0.005	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.014	0.079	-10000	0	-0.27	29	29
ACSS2	0.01	0.016	-10000	0	-0.27	1	1
SIRT1/PCAF/MYOD	0.026	0.042	0.22	2	-0.22	10	12

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.024	0.01	-10000	0	-10000	0	0
NFATC1	0.011	0.1	0.24	1	-0.43	9	10
NFATC2	0.021	0.057	0.14	7	-0.29	5	12
NFATC3	0.02	0.008	-10000	0	-10000	0	0
YWHAE	0.026	0.008	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.035	0.096	0.22	2	-0.32	26	28
Exportin 1/Ran/NUP214	0.054	0.014	-10000	0	-10000	0	0
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.021	0.099	-10000	0	-0.38	12	12
BCL2/BAX	0.035	0.021	-10000	0	-0.27	1	1
CaM/Ca2+/Calcineurin A alpha-beta B1	0.02	0.007	-10000	0	-10000	0	0
CaM/Ca2+	0.02	0.007	-10000	0	-10000	0	0
BAX	0.027	0.006	-10000	0	-10000	0	0
MAPK14	0.027	0.006	-10000	0	-10000	0	0
BAD	0.028	0.004	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.026	0.095	-10000	0	-0.34	18	18
Calcineurin A alpha-beta B1/BCL2	0.024	0.022	-10000	0	-0.38	1	1
FKBP8	0.027	0.005	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.026	0.094	0.33	18	-10000	0	18
KPNB1	0.028	0.002	-10000	0	-10000	0	0
KPNA2	0.027	0.019	-10000	0	-0.35	1	1
XPO1	0.028	0.003	-10000	0	-10000	0	0
SFN	0.015	0.067	-10000	0	-0.37	12	12
MAP3K8	0.026	0.02	-10000	0	-0.35	1	1
NFAT4/CK1 alpha	0.027	0.02	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	0.054	0.076	-10000	0	-0.3	3	3
CABIN1	-0.036	0.096	0.22	2	-0.32	26	28
CALM1	0.027	0.005	-10000	0	-10000	0	0
RAN	0.027	0.005	-10000	0	-10000	0	0
MAP3K1	0.026	0.008	-10000	0	-10000	0	0
CAMK4	0.016	0.063	-10000	0	-0.38	10	10
mol:Ca2+	0	0.002	-10000	0	-10000	0	0
MAPK3	0.027	0.005	-10000	0	-10000	0	0
YWHAH	0.027	0.005	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.036	0.033	-10000	0	-0.25	5	5
YWHAB	0.022	0.011	-10000	0	-10000	0	0
MAPK8	0.027	0.005	-10000	0	-10000	0	0
MAPK9	0.027	0.006	-10000	0	-10000	0	0
YWHAG	0.026	0.007	-10000	0	-10000	0	0
FKBP1A	0.025	0.009	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.032	0.11	0.24	4	-0.41	9	13
PRKCH	0.026	0.021	-10000	0	-0.38	1	1
CABIN1/Cbp/p300	0.036	0.017	-10000	0	-10000	0	0
CASP3	0.025	0.009	-10000	0	-10000	0	0
PIM1	0.025	0.029	-10000	0	-0.38	2	2
Calcineurin A alpha-beta B1/FKBP12/FK506	0.017	0.006	-10000	0	-10000	0	0
apoptosis	0.017	0.011	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.019	0.046	-10000	0	-0.45	1	1
PRKCB	0.003	0.096	-10000	0	-0.38	24	24
PRKCE	0.028	0.004	-10000	0	-10000	0	0
JNK2/NFAT4	0.026	0.04	-10000	0	-10000	0	0
BAD/BCL-XL	0.036	0.015	-10000	0	-10000	0	0
PRKCD	0.027	0.005	-10000	0	-10000	0	0
NUP214	0.027	0.005	-10000	0	-10000	0	0
PRKCZ	0.027	0.007	-10000	0	-10000	0	0
PRKCA	0.027	0.005	-10000	0	-10000	0	0
PRKCG	-0.13	0.19	-10000	0	-0.35	174	174
PRKCQ	0.011	0.077	-10000	0	-0.38	15	15
FKBP38/BCL2	0.035	0.021	-10000	0	-0.27	1	1
EP300	0.026	0.01	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.025	0.009	-10000	0	-10000	0	0
NFATc/JNK1	0.024	0.1	0.24	1	-0.42	8	9
CaM/Ca2+/FKBP38	0.035	0.012	-10000	0	-10000	0	0
FKBP12/FK506	0.019	0.007	-10000	0	-10000	0	0
CSNK1A1	0.013	0.007	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0.027	0.042	-10000	0	-0.22	10	10
NFATc/ERK1	0.025	0.1	0.24	1	-0.43	7	8
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.022	0.1	0.22	1	-0.37	13	14
NR4A1	0.024	0.088	0.22	7	-0.39	12	19
GSK3B	0.027	0.005	-10000	0	-10000	0	0
positive T cell selection	0.02	0.008	-10000	0	-10000	0	0
NFAT1/CK1 alpha	0.022	0.041	0.15	1	-0.23	2	3
RCH1/ KPNB1	0.04	0.016	-10000	0	-0.25	1	1
YWHAQ	0.028	0.004	-10000	0	-10000	0	0
PRKACA	0.027	0.005	-10000	0	-10000	0	0
AKAP5	0.023	0.042	-10000	0	-0.35	5	5
MEF2D	0.026	0.01	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.023	0.011	-10000	0	-10000	0	0
NFATc/p38 alpha	0.024	0.1	0.24	1	-0.42	8	9
CREBBP	0.025	0.011	-10000	0	-10000	0	0
BCL2	0.024	0.022	-10000	0	-0.38	1	1

×

TCGA08_rtk_signaling

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
PDGFRA	0.022	0.045	-10000	0	-0.38	5	5
HRAS	0.026	0.007	-10000	0	-10000	0	0
EGFR	0.017	0.057	-10000	0	-0.38	8	8
AKT	0.055	0.068	0.23	17	-0.24	1	18
FOXO3	0.027	0.006	-10000	0	-10000	0	0
AKT1	0.027	0.006	-10000	0	-10000	0	0
FOXO1	0.026	0.008	-10000	0	-10000	0	0
AKT3	0.026	0.019	-10000	0	-0.35	1	1
FOXO4	0.027	0.021	-10000	0	-0.38	1	1
MET	0.005	0.088	-10000	0	-0.36	23	23
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
PIK3CB	0.027	0.006	-10000	0	-10000	0	0
NRAS	0.027	0.005	-10000	0	-10000	0	0
PIK3CG	0.016	0.065	-10000	0	-0.38	11	11
PIK3R3	0.028	0.003	-10000	0	-10000	0	0
PIK3R2	0.027	0.005	-10000	0	-10000	0	0
NF1	0.028	0.004	-10000	0	-10000	0	0
RAS	0.025	0.052	0.16	5	-0.28	5	10
ERBB2	0.02	0.041	-10000	0	-0.38	4	4
proliferation/survival/translation	-0.041	0.054	0.27	2	-0.21	7	9
PI3K	0.038	0.061	0.21	20	-0.24	2	22
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
KRAS	0.025	0.009	-10000	0	-10000	0	0
FOXO	0.073	0.058	0.2	31	-10000	0	31
AKT2	0.027	0.006	-10000	0	-10000	0	0
PTEN	0.026	0.008	-10000	0	-10000	0	0

×

IL2 signaling events mediated by STAT5

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
GAB2	0.027	0.006	-10000	0	-10000	0	0
ELF1	0.014	0.059	-10000	0	-10000	0	0
CCNA2	0.027	0.005	-10000	0	-10000	0	0
PIK3CA	0.027	0.007	-10000	0	-10000	0	0
JAK3	0.011	0.078	-10000	0	-0.35	18	18
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
JAK1	0.028	0.004	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.031	0.07	0.24	2	-0.37	1	3
SHC1	0.028	0.005	-10000	0	-10000	0	0
SP1	0.025	0.047	-10000	0	-0.28	9	9
IL2RA	-0.011	0.092	-10000	0	-0.32	33	33
IL2RB	0.027	0.021	-10000	0	-0.38	1	1
SOS1	0.028	0.003	-10000	0	-10000	0	0
IL2RG	0.019	0.059	-10000	0	-0.37	9	9
G1/S transition of mitotic cell cycle	0.016	0.13	0.31	4	-0.69	8	12
PTPN11	0.028	0.004	-10000	0	-10000	0	0
CCND2	0.011	0.065	-10000	0	-0.64	4	4
LCK	0.017	0.062	-10000	0	-0.35	11	11
GRB2	0.028	0.005	-10000	0	-10000	0	0
IL2	0.021	0.027	-10000	0	-0.35	2	2
CDK6	0.021	0.038	-10000	0	-0.35	4	4
CCND3	0.038	0.083	0.35	4	-10000	0	4

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.091	0.18	-10000	0	-0.38	117	117
CLTC	0.015	0.071	-10000	0	-0.42	9	9
calcium ion-dependent exocytosis	0.015	0.03	0.2	1	-0.26	1	2
Dynamin 2/GTP	0.026	0.008	-10000	0	-10000	0	0
EXOC4	0.027	0.006	-10000	0	-10000	0	0
CD59	0.013	0.046	-10000	0	-0.33	6	6
CPE	-0.011	0.072	-10000	0	-0.23	42	42
CTNNB1	0.027	0.006	-10000	0	-10000	0	0
membrane fusion	0.016	0.021	-10000	0	-10000	0	0
CTNND1	0.015	0.031	0.2	11	-10000	0	11
DNM2	0.027	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.014	0.051	0.2	4	-0.36	4	8
TSHR	0.005	0.044	-10000	0	-0.23	14	14
INS	-0.006	0.11	-10000	0	-0.5	17	17
BIN1	0.028	0.003	-10000	0	-10000	0	0
mol:Choline	0.016	0.021	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.014	0.003	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.027	0.006	-10000	0	-10000	0	0
mol:Ca2+	0.026	0.008	-10000	0	-10000	0	0
JUP	0.016	0.048	-10000	0	-0.32	6	6
ASAP2/amphiphysin II	0.05	0.015	-10000	0	-10000	0	0
ARF6/GTP	0.02	0.004	-10000	0	-10000	0	0
CDH1	0.008	0.051	-10000	0	-0.33	6	6
clathrin-independent pinocytosis	0.02	0.004	-10000	0	-10000	0	0
MAPK8IP3	0.026	0.021	-10000	0	-0.38	1	1
positive regulation of endocytosis	0.02	0.004	-10000	0	-10000	0	0
EXOC2	0.026	0.007	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.019	0.042	-10000	0	-0.31	4	4
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.028	0.004	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.033	0.057	0.3	7	-10000	0	7
positive regulation of phagocytosis	0.013	0.004	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.034	0.017	-10000	0	-0.23	1	1
ACAP1	0.019	0.027	0.2	1	-0.21	1	2
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	-0.047	0.096	-10000	0	-0.46	7	7
clathrin heavy chain/ACAP1	0.018	0.059	0.36	1	-0.35	7	8
JIP4/KLC1	0.049	0.016	-10000	0	-10000	0	0
EXOC1	0.027	0.005	-10000	0	-10000	0	0
exocyst	0.02	0.039	-10000	0	-0.31	3	3
RALA/GTP	0.02	0.005	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.036	0.009	-10000	0	-10000	0	0
receptor recycling	0.02	0.004	-10000	0	-10000	0	0
CTNNA1	0.015	0.031	0.2	11	-10000	0	11
NME1	0.014	0.003	-10000	0	-10000	0	0
clathrin coat assembly	0.016	0.071	0.3	1	-0.41	9	10
IL2RA	0.006	0.052	-10000	0	-0.33	6	6
VAMP3	0.013	0.004	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.023	0.099	-10000	0	-0.36	9	9
EXOC6	0.027	0.006	-10000	0	-10000	0	0
PLD1	0.013	0.009	-10000	0	-10000	0	0
PLD2	0.013	0.007	-10000	0	-10000	0	0
EXOC5	0.028	0.004	-10000	0	-10000	0	0
PIP5K1C	0.012	0.045	0.19	1	-0.37	4	5
SDC1	0.012	0.047	-10000	0	-0.32	6	6
ARF6/GDP	0.025	0.006	-10000	0	-10000	0	0
EXOC7	0.028	0.004	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.036	0.059	-10000	0	-0.3	7	7
mol:Phosphatidic acid	0.016	0.021	-10000	0	-10000	0	0
endocytosis	-0.048	0.014	-10000	0	-10000	0	0
SCAMP2	0.027	0.005	-10000	0	-10000	0	0
ADRB2	-0.032	0.1	0.22	1	-0.39	12	13
EXOC3	0.025	0.009	-10000	0	-10000	0	0
ASAP2	0.027	0.005	-10000	0	-10000	0	0
Dynamin 2/GDP	0.03	0.009	-10000	0	-10000	0	0
KLC1	0.027	0.006	-10000	0	-10000	0	0
AVPR2	0.007	0.087	0.27	7	-0.41	8	15
RALA	0.027	0.006	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.03	0.057	-10000	0	-0.32	3	3

×

Insulin 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	0.023	0.077	-10000	0	-0.36	1	1
TC10/GTP	0.018	0.071	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	0.067	0.032	-10000	0	-0.22	1	1
HRAS	0.026	0.007	-10000	0	-10000	0	0
APS homodimer	0.024	0.027	-10000	0	-0.35	2	2
GRB14	-0.037	0.14	-10000	0	-0.36	68	68
FOXO3	0.003	0.11	-10000	0	-0.55	16	16
AKT1	-0.013	0.08	0.26	7	-10000	0	7
INSR	0.033	0.014	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.063	0.053	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.026	0.02	-10000	0	-0.35	1	1
SORBS1	-0.022	0.13	-10000	0	-0.38	49	49
CRK	0.026	0.008	-10000	0	-10000	0	0
PTPN1	0.006	0.02	-10000	0	-10000	0	0
CAV1	0.001	0.039	0.18	8	-0.2	1	9
CBL/APS/CAP/Crk-II/C3G	0.037	0.086	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1/NCK2	0.066	0.032	-10000	0	-0.22	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.048	0.029	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.033	0.084	-10000	0	-0.37	4	4
RPS6KB1	-0.015	0.074	0.24	9	-10000	0	9
PARD6A	0.027	0.006	-10000	0	-10000	0	0
CBL	0.027	0.006	-10000	0	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.019	0.029	-10000	0	-0.52	1	1
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	0.016	0.072	-10000	0	-10000	0	0
HRAS/GTP	0.018	0.021	-10000	0	-10000	0	0
Insulin Receptor	0.033	0.014	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.074	0.037	-10000	0	-10000	0	0
PRKCI	0.014	0.066	-10000	0	-0.38	2	2
Insulin Receptor/Insulin/GRB14/PDK1	0.003	0.069	-10000	0	-10000	0	0
SHC1	0.027	0.005	-10000	0	-10000	0	0
negative regulation of MAPKKK cascade	0.043	0.034	-10000	0	-0.44	1	1
PI3K	0.059	0.034	-10000	0	-10000	0	0
NCK2	0.028	0.004	-10000	0	-10000	0	0
RHOQ	0.028	0.002	-10000	0	-10000	0	0
mol:H2O2	0.001	0.005	-10000	0	-10000	0	0
HRAS/GDP	0.02	0.005	-10000	0	-10000	0	0
AKT2	-0.013	0.077	0.24	8	-10000	0	8
PRKCZ	0.009	0.079	-10000	0	-0.39	4	4
SH2B2	0.024	0.027	-10000	0	-0.35	2	2
SHC/SHIP	0.035	0.035	0.2	6	-10000	0	6
F2RL2	-0.03	0.14	-10000	0	-0.35	61	61
TRIP10	0.027	0.006	-10000	0	-10000	0	0
Insulin Receptor/Insulin/Shc	0.052	0.024	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.036	0.009	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.076	0.034	-10000	0	-10000	0	0
RAPGEF1	0.027	0.005	-10000	0	-10000	0	0
RASA1	0.025	0.008	-10000	0	-10000	0	0
NCK1	0.027	0.005	-10000	0	-10000	0	0
CBL/APS/CAP/Crk-II	0.029	0.085	-10000	0	-0.21	36	36
TC10/GDP	0.021	0.002	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.063	0.032	-10000	0	-10000	0	0
INPP5D	0.002	0.039	0.18	8	-0.2	2	10
SOS1	0.028	0.003	-10000	0	-10000	0	0
SGK1	-0.002	0.11	-10000	0	-0.67	10	10
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.028	0.004	-10000	0	-10000	0	0
IRS1	0.027	0.021	-10000	0	-0.38	1	1
p62DOK/RasGAP	0.043	0.034	-10000	0	-0.45	1	1
INS	0.025	0.013	-10000	0	-10000	0	0
mol:PI-3-4-P2	0.002	0.039	0.18	8	-0.2	2	10
GRB2	0.027	0.005	-10000	0	-10000	0	0
EIF4EBP1	-0.016	0.069	0.24	6	-10000	0	6
PTPRA	0.029	0.012	-10000	0	-10000	0	0
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
TC10/GTP/CIP4	0.036	0.009	-10000	0	-10000	0	0
PDPK1	0.027	0.007	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.027	0.028	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.051	0.027	-10000	0	-0.22	1	1
Insulin Receptor/Insulin/IRS3	0.043	0.023	-10000	0	-10000	0	0
Par3/Par6	0.021	0.085	-10000	0	-0.18	56	56

×

Signaling events mediated by PRL

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
CCNE1	0.011	0.071	-10000	0	-0.35	15	15
mol:Halofuginone	0.003	0	-10000	0	-10000	0	0
ITGA1	0.018	0.056	-10000	0	-0.35	9	9
CDKN1A	0.01	0.052	-10000	0	-0.54	1	1
PRL-3/alpha Tubulin	0.035	0.016	-10000	0	-10000	0	0
mol:Ca2+	-0.048	0.079	-10000	0	-0.26	52	52
AGT	-0.022	0.13	-10000	0	-0.36	53	53
CCNA2	-0.006	0.024	-10000	0	-10000	0	0
TUBA1B	0.028	0.004	-10000	0	-10000	0	0
EGR1	0.008	0.042	-10000	0	-0.26	10	10
CDK2/Cyclin E1	0.037	0.082	-10000	0	-0.42	3	3
MAPK3	0.011	0.005	-10000	0	-10000	0	0
PRL-2 /Rab GGTase beta	0.04	0.009	-10000	0	-10000	0	0
MAPK1	0.011	0.005	-10000	0	-10000	0	0
PTP4A1	-0.001	0.028	-10000	0	-10000	0	0
PTP4A3	0.024	0.01	-10000	0	-10000	0	0
PTP4A2	0.027	0.005	-10000	0	-10000	0	0
ITGB1	0.011	0.014	-10000	0	-0.25	1	1
SRC	0.024	0.01	-10000	0	-10000	0	0
RAC1	0.013	0.031	-10000	0	-0.3	3	3
Rab GGTase beta/Rab GGTase alpha	0.04	0.009	-10000	0	-10000	0	0
PRL-1/ATF-5	0.036	0.065	-10000	0	-10000	0	0
RABGGTA	0.028	0.004	-10000	0	-10000	0	0
BCAR1	-0.017	0.008	-10000	0	-10000	0	0
RHOC	0.011	0.045	-10000	0	-0.47	1	1
RHOA	0.011	0.045	-10000	0	-0.33	6	6
cell motility	0.039	0.069	0.3	4	-0.31	2	6
PRL-1/alpha Tubulin	0.038	0.065	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	0.027	0.044	-10000	0	-0.25	9	9
ROCK1	0.039	0.061	0.28	3	-0.3	1	4
RABGGTB	0.027	0.005	-10000	0	-10000	0	0
CDK2	0.027	0.006	-10000	0	-10000	0	0
mitosis	-0.001	0.028	-10000	0	-10000	0	0
ATF5	0.026	0.019	-10000	0	-0.35	1	1

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0.015	0.049	0.22	3	-0.27	1	4
adherens junction organization	0.018	0.074	0.22	4	-0.37	6	10
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.026	0.059	0.23	4	-0.27	1	5
FMN1	0.016	0.069	-10000	0	-0.36	5	5
mol:IP3	0.011	0.038	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.021	0.069	-10000	0	-0.34	6	6
CTNNB1	0.027	0.007	-10000	0	-10000	0	0
AKT1	0.027	0.055	0.2	8	-10000	0	8
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.014	0.12	-10000	0	-0.46	14	14
CTNND1	0.03	0.006	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.018	0.068	0.18	5	-0.32	6	11
VASP	0.018	0.063	-10000	0	-0.32	5	5
ZYX	0.019	0.061	0.16	1	-0.32	4	5
JUB	0.018	0.066	0.16	3	-0.32	6	9
EGFR(dimer)	0.028	0.078	0.22	2	-0.32	8	10
E-cadherin/beta catenin-gamma catenin	0.041	0.043	-10000	0	-0.21	9	9
mol:PI-3-4-5-P3	0.046	0.069	0.23	9	-0.24	1	10
PIK3CA	0.028	0.008	-10000	0	-10000	0	0
PI3K	0.047	0.07	0.23	9	-0.25	1	10
FYN	-0.001	0.063	0.24	2	-0.34	3	5
mol:Ca2+	0.011	0.037	-10000	0	-10000	0	0
JUP	0.026	0.009	-10000	0	-10000	0	0
PIK3R1	0.028	0.009	-10000	0	-10000	0	0
mol:DAG	0.011	0.038	-10000	0	-10000	0	0
CDH1	0.018	0.06	-10000	0	-0.38	9	9
RhoA/GDP	0.029	0.06	0.23	6	-0.25	1	7
establishment of polarity of embryonic epithelium	0.02	0.064	0.2	3	-0.31	5	8
SRC	0.024	0.01	-10000	0	-10000	0	0
RAC1	0.026	0.008	-10000	0	-10000	0	0
RHOA	0.027	0.006	-10000	0	-10000	0	0
EGFR	0.017	0.057	-10000	0	-0.38	8	8
CASR	-0.004	0.06	0.21	1	-0.3	2	3
RhoA/GTP	0.024	0.044	-10000	0	-10000	0	0
AKT2	0.027	0.057	0.2	9	-0.24	1	10
actin cable formation	0.016	0.073	0.2	10	-0.34	6	16
apoptosis	-0.031	0.068	0.27	2	-0.23	12	14
CTNNA1	0.029	0.008	-10000	0	-10000	0	0
mol:GDP	0.009	0.05	0.24	1	-0.28	1	2
PIP5K1A	0.017	0.067	0.16	1	-0.32	6	7
PLCG1	0.011	0.038	-10000	0	-10000	0	0
Rac1/GTP	0.033	0.076	0.21	2	-0.31	7	9
homophilic cell adhesion	0.001	0.004	-10000	0	-10000	0	0

×

E-cadherin signaling events

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
E-cadherin/beta catenin-gamma catenin	0.042	0.045	-9999	-0.23	9	9
E-cadherin/beta catenin	0.031	0.046	-9999	-0.27	9	9
CTNNB1	0.027	0.006	-9999	-10000	0	0
JUP	0.026	0.008	-9999	-10000	0	0
CDH1	0.018	0.06	-9999	-0.38	9	9

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.02	0.013	-10000	0	-10000	0	0
TRAF2/ASK1	0.035	0.01	-10000	0	-10000	0	0
ATM	0.026	0.02	-10000	0	-0.35	1	1
MAP2K3	-0.01	0.098	0.21	2	-0.34	17	19
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	-0.001	0.086	0.22	2	-0.39	7	9
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.025	0.028	-10000	0	-0.37	2	2
TXN	0.007	0.001	-10000	0	-10000	0	0
CALM1	0.027	0.005	-10000	0	-10000	0	0
GADD45A	0.028	0.004	-10000	0	-10000	0	0
GADD45B	0.027	0.006	-10000	0	-10000	0	0
MAP3K1	0.026	0.008	-10000	0	-10000	0	0
MAP3K6	0.027	0.006	-10000	0	-10000	0	0
MAP3K7	0.027	0.006	-10000	0	-10000	0	0
MAP3K4	0.027	0.006	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.039	0.011	-10000	0	-10000	0	0
TAK1/TAB family	-0.001	0.016	-10000	0	-0.13	1	1
RAC1/OSM/MEKK3	0.048	0.017	-10000	0	-10000	0	0
TRAF2	0.027	0.006	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.006	0.084	-10000	0	-0.32	7	7
TRAF6	0.007	0.001	-10000	0	-10000	0	0
RAC1	0.026	0.008	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.047	0.16	-10000	0	-0.38	73	73
CCM2	0.026	0.007	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.012	0.099	-10000	0	-0.22	73	73
MAPK11	0.026	0.007	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.003	0.097	-10000	0	-0.2	71	71
OSM/MEKK3	0.038	0.012	-10000	0	-10000	0	0
TAOK1	0.014	0.009	-10000	0	-10000	0	0
TAOK2	0.014	0.009	-10000	0	-0.14	1	1
TAOK3	0.014	0.009	-10000	0	-0.14	1	1
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.027	0.006	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.027	0.005	-10000	0	-10000	0	0
MAP3K10	0.027	0.006	-10000	0	-10000	0	0
MAP3K3	0.027	0.005	-10000	0	-10000	0	0
TRX/ASK1	0.024	0.015	-10000	0	-10000	0	0
GADD45/MTK1/MTK1	0.057	0.028	-10000	0	-0.2	1	1

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	-0.049	0.16	0.26	1	-0.4	35	36
CaM/Ca2+	0.02	0.004	-10000	0	-10000	0	0
AKT1	0.027	0.006	-10000	0	-10000	0	0
AKT2	0.027	0.006	-10000	0	-10000	0	0
STXBP4	0.028	0.001	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	-0.067	0.16	0.26	2	-0.42	42	44
YWHAZ	0.023	0.011	-10000	0	-10000	0	0
CALM1	0.027	0.005	-10000	0	-10000	0	0
YWHAQ	0.028	0.004	-10000	0	-10000	0	0
TBC1D4	0.009	0.03	-10000	0	-0.24	6	6
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.027	0.005	-10000	0	-10000	0	0
YWHAB	0.022	0.011	-10000	0	-10000	0	0
SNARE/Synip	0.052	0.017	-10000	0	-10000	0	0
YWHAG	0.026	0.007	-10000	0	-10000	0	0
ASIP	0.016	0.053	-10000	0	-0.35	8	8
PRKCI	0.024	0.027	-10000	0	-0.35	2	2
AS160/CaM/Ca2+	0.02	0.004	-10000	0	-10000	0	0
RHOQ	0.028	0.002	-10000	0	-10000	0	0
GYS1	0.012	0.02	0.24	3	-10000	0	3
PRKCZ	0.026	0.007	-10000	0	-10000	0	0
TRIP10	0.027	0.006	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.036	0.009	-10000	0	-10000	0	0
AS160/14-3-3	0.015	0.05	-10000	0	-0.29	3	3
VAMP2	0.026	0.007	-10000	0	-10000	0	0
SLC2A4	-0.075	0.18	0.26	2	-0.47	42	44
STX4	0.027	0.005	-10000	0	-10000	0	0
GSK3B	0.02	0.007	-10000	0	-10000	0	0
SFN	0.015	0.067	-10000	0	-0.37	12	12
LNPEP	0.026	0.008	-10000	0	-10000	0	0
YWHAE	0.026	0.008	-10000	0	-10000	0	0

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.031	0.018	-10000	0	-0.28	1	1
VEGFR1 homodimer/NRP1	0.012	0.015	-10000	0	-0.27	1	1
mol:DAG	0.011	0.041	0.19	9	-10000	0	9
VEGFR1 homodimer/NRP1/VEGFR 121	0.026	0.016	-10000	0	-10000	0	0
CaM/Ca2+	0.024	0.042	-10000	0	-10000	0	0
HIF1A	0.032	0.012	-10000	0	-0.18	1	1
GAB1	0.027	0.006	-10000	0	-10000	0	0
AKT1	0.019	0.059	0.32	4	-10000	0	4
PLCG1	0.011	0.041	0.2	9	-10000	0	9
NOS3	0.029	0.079	0.3	11	-0.44	2	13
CBL	0.027	0.006	-10000	0	-10000	0	0
mol:NO	0.03	0.086	0.3	13	-0.42	3	16
FLT1	0.016	0.018	-10000	0	-0.32	1	1
PGF	0.015	0.067	-10000	0	-0.35	13	13
VEGFR1 homodimer/NRP2/VEGFR121	0.041	0.026	-10000	0	-10000	0	0
CALM1	0.027	0.005	-10000	0	-10000	0	0
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
eNOS/Hsp90	0.043	0.092	0.3	13	-0.39	5	18
endothelial cell proliferation	0.022	0.079	0.32	10	-10000	0	10
mol:Ca2+	0.01	0.041	0.19	9	-10000	0	9
MAPK3	-0.008	0.037	0.17	9	-10000	0	9
MAPK1	-0.008	0.037	0.17	9	-10000	0	9
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
PLGF homodimer	0.015	0.067	-10000	0	-0.35	13	13
PRKACA	0.027	0.005	-10000	0	-10000	0	0
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	0.024	0.033	-10000	0	-0.35	3	3
VEGFA homodimer	0.025	0.02	-10000	0	-0.35	1	1
VEGFR1 homodimer/VEGFA homodimer	0.029	0.018	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	-0.01	0.035	0.16	9	-10000	0	9
PI3K	0.046	0.049	-10000	0	-10000	0	0
PRKCA	-0.007	0.038	0.18	8	-10000	0	8
PRKCB	-0.014	0.051	0.18	8	-10000	0	8
VEGFR1 homodimer/PLGF homodimer	0.024	0.044	-10000	0	-0.28	1	1
VEGFA	0.025	0.02	-10000	0	-0.35	1	1
VEGFB	0.028	0.004	-10000	0	-10000	0	0
mol:IP3	0.011	0.041	0.19	9	-10000	0	9
RASA1	0.02	0.039	0.2	17	-0.25	1	18
NRP2	0.027	0.019	-10000	0	-0.35	1	1
VEGFR1 homodimer	0.016	0.018	-10000	0	-0.32	1	1
VEGFB homodimer	0.028	0.004	-10000	0	-10000	0	0
NCK1	0.027	0.005	-10000	0	-10000	0	0
eNOS/Caveolin-1	0.038	0.086	0.28	11	-0.41	3	14
PTPN11	0.028	0.004	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.044	0.048	-10000	0	-0.24	1	1
mol:L-citrulline	0.03	0.086	0.3	13	-0.42	3	16
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.052	0.029	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.041	0.023	-10000	0	-10000	0	0
CD2AP	0.026	0.007	-10000	0	-10000	0	0
PI3K/GAB1	0.06	0.056	-10000	0	-10000	0	0
PDPK1	0.02	0.061	0.34	3	-10000	0	3
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.042	0.023	-10000	0	-10000	0	0
mol:NADP	0.03	0.086	0.3	13	-0.42	3	16
HSP90AA1	0.025	0.027	-10000	0	-0.35	2	2
ubiquitin-dependent protein catabolic process	0.05	0.028	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP2	0.03	0.022	-10000	0	-0.28	1	1

×

Class IB PI3K non-lipid kinase 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
cAMP biosynthetic process	-0.025	0.033	0.36	3	-10000	0	3
PI3K Class IB/PDE3B	0.025	0.033	-10000	0	-0.36	3	3
PDE3B	0.025	0.033	-10000	0	-0.36	3	3

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.029	0.006	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.044	0.083	0.21	17	-0.35	4	21
ERC1	0.026	0.007	-10000	0	-10000	0	0
RIP2/NOD2	0.032	0.032	-10000	0	-0.25	4	4
NFKBIA	0.015	0.024	0.21	6	-10000	0	6
BIRC2	0.027	0.006	-10000	0	-10000	0	0
IKBKB	0.025	0.009	-10000	0	-10000	0	0
RIPK2	0.024	0.01	-10000	0	-10000	0	0
IKBKG	0.032	0.03	-10000	0	-10000	0	0
IKK complex/A20	0.039	0.093	0.26	1	-0.4	5	6
NEMO/A20/RIP2	0.024	0.01	-10000	0	-10000	0	0
XPO1	0.028	0.003	-10000	0	-10000	0	0
NEMO/ATM	0.036	0.088	0.26	2	-0.38	10	12
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.027	0.005	-10000	0	-10000	0	0
Exportin 1/RanGTP	0.037	0.007	-10000	0	-10000	0	0
IKK complex/ELKS	0.036	0.079	-10000	0	-0.39	5	5
BCL10/MALT1/TRAF6	0.049	0.02	-10000	0	-10000	0	0
NOD2	0.022	0.043	-10000	0	-0.36	5	5
NFKB1	0.029	0.005	-10000	0	-10000	0	0
RELA	0.029	0.005	-10000	0	-10000	0	0
MALT1	0.025	0.009	-10000	0	-10000	0	0
cIAP1/UbcH5C	0.039	0.01	-10000	0	-10000	0	0
ATM	0.026	0.02	-10000	0	-0.35	1	1
TNF/TNFR1A	0.025	0.059	-10000	0	-0.25	17	17
TRAF6	0.027	0.005	-10000	0	-10000	0	0
PRKCA	0.027	0.005	-10000	0	-10000	0	0
CHUK	0.027	0.006	-10000	0	-10000	0	0
UBE2D3	0.027	0.005	-10000	0	-10000	0	0
TNF	0.01	0.08	-10000	0	-0.36	18	18
NF kappa B1 p50/RelA	0.058	0.019	-10000	0	-10000	0	0
BCL10	0.028	0.004	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.015	0.024	0.21	6	-10000	0	6
beta TrCP1/SCF ubiquitin ligase complex	0.029	0.006	-10000	0	-10000	0	0
TNFRSF1A	0.027	0.006	-10000	0	-10000	0	0
IKK complex	0.042	0.087	0.27	2	-0.42	5	7
CYLD	0.027	0.006	-10000	0	-10000	0	0
IKK complex/PKC alpha	0.051	0.086	0.26	2	-0.41	4	6

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.026	0.02	-9999	-0.35	1	1
ITGB7	0.026	0.021	-9999	-0.38	1	1
ITGA4	0.025	0.033	-9999	-0.35	3	3
alpha4/beta7 Integrin	0.036	0.03	-9999	-0.25	4	4
alpha4/beta1 Integrin	0.036	0.03	-9999	-0.25	4	4

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.019	0.035	-10000	0	-10000	0	0
regulation of axonogenesis	-0.009	0.024	0.24	3	-10000	0	3
myoblast fusion	-0.022	0.035	0.31	2	-10000	0	2
mol:GTP	0.018	0.026	-10000	0	-0.15	7	7
regulation of calcium-dependent cell-cell adhesion	-0.043	0.048	0.21	8	-10000	0	8
ARF1/GTP	0.033	0.026	-10000	0	-10000	0	0
mol:GM1	0.008	0.019	-10000	0	-10000	0	0
mol:Choline	0.008	0.018	-10000	0	-0.19	1	1
lamellipodium assembly	0.011	0.05	-10000	0	-0.34	6	6
MAPK3	0.021	0.023	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.044	0.049	-10000	0	-0.21	8	8
ARF1	0.027	0.005	-10000	0	-10000	0	0
ARF6/GDP	0.022	0.036	-10000	0	-0.31	2	2
ARF1/GDP	0.026	0.045	-10000	0	-0.28	3	3
ARF6	0.033	0.014	-10000	0	-10000	0	0
RAB11A	0.027	0.005	-10000	0	-10000	0	0
TIAM1	0.017	0.062	-10000	0	-0.37	10	10
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.021	0.023	-10000	0	-10000	0	0
actin filament bundle formation	-0.03	0.044	0.27	3	-10000	0	3
KALRN	0.012	0.03	-10000	0	-0.23	4	4
RAB11FIP3/RAB11A	0.038	0.012	-10000	0	-10000	0	0
RhoA/GDP	0.03	0.044	-10000	0	-0.27	3	3
NME1	0.028	0.006	-10000	0	-10000	0	0
Rac1/GDP	0.028	0.045	-10000	0	-0.28	3	3
substrate adhesion-dependent cell spreading	0.018	0.026	-10000	0	-0.15	7	7
cortical actin cytoskeleton organization	0.011	0.05	-10000	0	-0.34	6	6
RAC1	0.026	0.008	-10000	0	-10000	0	0
liver development	0.018	0.026	-10000	0	-0.15	7	7
ARF6/GTP	0.018	0.026	-10000	0	-0.15	7	7
RhoA/GTP	0.033	0.026	-10000	0	-10000	0	0
mol:GDP	0.012	0.034	-10000	0	-0.24	2	2
ARF6/GTP/RAB11FIP3/RAB11A	0.047	0.028	-10000	0	-10000	0	0
RHOA	0.027	0.006	-10000	0	-10000	0	0
PLD1	0.016	0.024	-10000	0	-0.22	1	1
RAB11FIP3	0.027	0.007	-10000	0	-10000	0	0
tube morphogenesis	0.011	0.05	-10000	0	-0.34	6	6
ruffle organization	0.009	0.024	-10000	0	-0.24	3	3
regulation of epithelial cell migration	0.018	0.026	-10000	0	-0.15	7	7
PLD2	0.017	0.02	-10000	0	-10000	0	0
PIP5K1A	0.009	0.024	-10000	0	-0.24	3	3
mol:Phosphatidic acid	0.008	0.018	-10000	0	-0.19	1	1
Rac1/GTP	0.011	0.05	-10000	0	-0.34	6	6

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	0.035	0.033	-10000	0	-0.25	5	5
AKT1	0.055	0.077	0.31	16	-10000	0	16
PTK2B	0.023	0.047	-10000	0	-10000	0	0
VEGFR2 homodimer/Frs2	0.034	0.012	-10000	0	-10000	0	0
CAV1	0.024	0.033	-10000	0	-0.35	3	3
CALM1	0.027	0.005	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.045	0.024	-10000	0	-10000	0	0
endothelial cell proliferation	0.066	0.1	0.27	50	-10000	0	50
mol:Ca2+	0.02	0.027	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.055	0.031	-10000	0	-10000	0	0
RP11-342D11.1	0.01	0.02	-10000	0	-10000	0	0
CDH5	0.027	0.006	-10000	0	-10000	0	0
VEGFA homodimer	0.061	0.03	-10000	0	-0.19	1	1
SHC1	0.027	0.005	-10000	0	-10000	0	0
SHC2	0.021	0.05	-10000	0	-0.38	6	6
HRAS/GDP	0.043	0.025	-10000	0	-10000	0	0
SH2D2A	0.026	0.019	-10000	0	-0.35	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.052	0.094	0.27	3	-0.45	5	8
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.046	0.025	-10000	0	-10000	0	0
VEGFR1 homodimer	0.025	0.02	-10000	0	-0.35	1	1
SHC/GRB2/SOS1	0.07	0.035	-10000	0	-10000	0	0
GRB10	0.021	0.03	-10000	0	-10000	0	0
PTPN11	0.028	0.004	-10000	0	-10000	0	0
GRB2	0.027	0.005	-10000	0	-10000	0	0
PAK1	0.027	0.005	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.065	0.036	-10000	0	-10000	0	0
HRAS	0.026	0.007	-10000	0	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	0.019	0.047	-10000	0	-0.29	2	2
HIF1A	0.027	0.005	-10000	0	-10000	0	0
FRS2	0.026	0.007	-10000	0	-10000	0	0
oxygen and reactive oxygen species metabolic process	0.053	0.03	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.027	0.006	-10000	0	-10000	0	0
Nck/Pak	0.039	0.011	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.047	0.022	-10000	0	-10000	0	0
mol:GDP	0.056	0.029	-10000	0	-10000	0	0
mol:NADP	0.048	0.1	0.28	18	-0.43	6	24
eNOS/Hsp90	0.058	0.1	0.28	18	-0.42	5	23
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
mol:IP3	0.02	0.027	-10000	0	-10000	0	0
HIF1A/ARNT	0.039	0.011	-10000	0	-10000	0	0
SHB	0.026	0.007	-10000	0	-10000	0	0
VEGFA	0.026	0.02	-10000	0	-0.35	1	1
VEGFC	0.025	0.021	-10000	0	-0.38	1	1
FAK1/Vinculin	0.055	0.073	0.28	7	-10000	0	7
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.027	0.006	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.055	0.039	-10000	0	-10000	0	0
PTPN6	0.026	0.02	-10000	0	-0.35	1	1
EPAS1	0.034	0.005	-10000	0	-10000	0	0
mol:L-citrulline	0.048	0.1	0.28	18	-0.43	6	24
ITGAV	0.026	0.007	-10000	0	-10000	0	0
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.056	0.03	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer	0.05	0.025	-10000	0	-10000	0	0
VEGFR2/3 heterodimer	0.035	0.01	-10000	0	-10000	0	0
VEGFB	0.028	0.004	-10000	0	-10000	0	0
MAPK11	0.016	0.051	0.24	3	-10000	0	3
VEGFR2 homodimer	0.021	0.004	-10000	0	-10000	0	0
FLT1	0.025	0.02	-10000	0	-0.35	1	1
NEDD4	0.028	0.006	-10000	0	-10000	0	0
MAPK3	0.031	0.083	0.33	14	-10000	0	14
MAPK1	0.03	0.081	0.32	14	-10000	0	14
VEGFA145/NRP2	0.037	0.024	-10000	0	-0.24	2	2
VEGFR1/2 heterodimer	0.033	0.016	-10000	0	-10000	0	0
KDR	0.021	0.004	-10000	0	-10000	0	0
VEGFA165/NRP1/VEGFR2 homodimer	0.049	0.027	-10000	0	-10000	0	0
SRC	0.024	0.01	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	0.039	0.088	0.32	18	-10000	0	18
PI3K	0.039	0.042	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.047	0.023	-10000	0	-10000	0	0
FES	0.02	0.033	-10000	0	-10000	0	0
GAB1	0.034	0.027	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src	0.042	0.026	-10000	0	-10000	0	0
CTNNB1	0.027	0.006	-10000	0	-10000	0	0
SOS1	0.028	0.003	-10000	0	-10000	0	0
ARNT	0.027	0.006	-10000	0	-10000	0	0
eNOS/Caveolin-1	0.055	0.097	0.29	15	-0.4	5	20
VEGFR2 homodimer/VEGFA homodimer/Yes	0.046	0.023	-10000	0	-10000	0	0
PI3K/GAB1	0.046	0.052	0.28	1	-10000	0	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.065	0.037	-10000	0	-10000	0	0
PRKACA	0.027	0.005	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.047	0.021	-10000	0	-10000	0	0
HSP90AA1	0.025	0.027	-10000	0	-0.35	2	2
CDC42	0.023	0.025	-10000	0	-10000	0	0
actin cytoskeleton reorganization	0.046	0.025	-10000	0	-10000	0	0
PTK2	0.028	0.047	0.24	5	-10000	0	5
EDG1	0.01	0.02	-10000	0	-10000	0	0
mol:DAG	0.02	0.027	-10000	0	-10000	0	0
CaM/Ca2+	0.035	0.035	-10000	0	-10000	0	0
MAP2K3	0.017	0.044	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.055	0.046	-10000	0	-10000	0	0
PLCG1	0.02	0.027	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.051	0.033	-10000	0	-10000	0	0
IQGAP1	0.026	0.007	-10000	0	-10000	0	0
YES1	0.026	0.007	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.047	0.022	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.045	0.026	-10000	0	-10000	0	0
cell migration	0.06	0.078	0.28	18	-10000	0	18
mol:PI-3-4-5-P3	0.039	0.041	-10000	0	-10000	0	0
FYN	0.027	0.005	-10000	0	-10000	0	0
VEGFB/NRP1	0.028	0.026	-10000	0	-10000	0	0
mol:NO	0.048	0.1	0.28	18	-0.43	6	24
PXN	0.027	0.005	-10000	0	-10000	0	0
HRAS/GTP	0.026	0.016	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.039	0.027	-10000	0	-10000	0	0
VHL	0.028	0.004	-10000	0	-10000	0	0
ITGB3	0.023	0.042	-10000	0	-0.36	5	5
NOS3	0.048	0.11	0.29	17	-0.49	6	23
VEGFR2 homodimer/VEGFA homodimer/Sck	0.043	0.036	-10000	0	-10000	0	0
RAC1	0.026	0.008	-10000	0	-10000	0	0
PRKCA	0.016	0.037	-10000	0	-10000	0	0
PRKCB	0.007	0.052	-10000	0	-10000	0	0
VCL	0.026	0.007	-10000	0	-10000	0	0
VEGFA165/NRP1	0.029	0.022	-10000	0	-10000	0	0
VEGFR1/2 heterodimer/VEGFA homodimer	0.046	0.023	-10000	0	-10000	0	0
VEGFA165/NRP2	0.037	0.024	-10000	0	-0.24	2	2
MAPKKK cascade	0.032	0.031	-10000	0	-10000	0	0
NRP2	0.027	0.019	-10000	0	-0.35	1	1
VEGFC homodimer	0.025	0.021	-10000	0	-0.38	1	1
NCK1	0.027	0.005	-10000	0	-10000	0	0
ROCK1	0.027	0.006	-10000	0	-10000	0	0
FAK1/Paxillin	0.058	0.073	0.28	6	-10000	0	6
MAP3K13	0.02	0.029	-10000	0	-10000	0	0
PDPK1	0.034	0.049	0.25	8	-10000	0	8

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	0.062	0.028	-9999	-0.19	1	1
HDAC3	0.027	0.006	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.008	0.002	-9999	-10000	0	0
GATA1/HDAC4	0.034	0.038	-9999	-0.27	6	6
GATA1/HDAC5	0.034	0.038	-9999	-0.27	6	6
GATA2/HDAC5	0.036	0.035	-9999	-0.27	5	5
HDAC5/BCL6/BCoR	0.052	0.016	-9999	-10000	0	0
HDAC9	0.008	0.084	-9999	-0.38	18	18
Glucocorticoid receptor/Hsp90/HDAC6	0.047	0.039	-9999	-0.22	7	7
HDAC4/ANKRA2	0.038	0.013	-9999	-10000	0	0
HDAC5/YWHAB	0.033	0.017	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.014	0.005	-9999	-10000	0	0
GATA2	0.022	0.045	-9999	-0.38	5	5
HDAC4/RFXANK	0.039	0.01	-9999	-10000	0	0
BCOR	0.028	0.004	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.026	0.007	-9999	-10000	0	0
HDAC5	0.028	0.004	-9999	-10000	0	0
GNB1/GNG2	0.038	0.018	-9999	-0.25	1	1
Histones	0.017	0.054	-9999	-0.27	2	2
ADRBK1	0.027	0.006	-9999	-10000	0	0
HDAC4	0.027	0.005	-9999	-10000	0	0
XPO1	0.028	0.003	-9999	-10000	0	0
HDAC5/ANKRA2	0.038	0.012	-9999	-10000	0	0
HDAC4/Ubc9	0.038	0.012	-9999	-10000	0	0
HDAC7	0.027	0.005	-9999	-10000	0	0
HDAC5/14-3-3 E	0.038	0.013	-9999	-10000	0	0
TUBA1B	0.028	0.004	-9999	-10000	0	0
HDAC6	0.028	0.004	-9999	-10000	0	0
HDAC5/RFXANK	0.04	0.009	-9999	-10000	0	0
CAMK4	0.016	0.063	-9999	-0.38	10	10
Tubulin/HDAC6	0.051	0.022	-9999	-0.23	1	1
SUMO1	0.028	0.003	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.022	0.011	-9999	-10000	0	0
GATA1	0.02	0.049	-9999	-0.38	6	6
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.026	0.008	-9999	-10000	0	0
NR3C1	0.022	0.045	-9999	-0.38	5	5
SUMO1/HDAC4	0.036	0.035	-9999	-10000	0	0
SRF	0.026	0.008	-9999	-10000	0	0
HDAC4/YWHAB	0.032	0.018	-9999	-10000	0	0
Tubulin	0.038	0.019	-9999	-0.27	1	1
HDAC4/14-3-3 E	0.037	0.013	-9999	-10000	0	0
GNB1	0.026	0.007	-9999	-10000	0	0
RANGAP1	0.027	0.005	-9999	-10000	0	0
BCL6/BCoR	0.039	0.011	-9999	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0.051	0.018	-9999	-10000	0	0
HDAC4/SRF	0.04	0.047	-9999	-0.23	10	10
HDAC4/ER alpha	0.027	0.059	-9999	-0.27	15	15
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.017	0.054	-9999	-0.27	2	2
cell motility	0.051	0.022	-9999	-0.23	1	1
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.026	0.007	-9999	-10000	0	0
HDAC7/HDAC3	0.038	0.012	-9999	-10000	0	0
BCL6	0.027	0.006	-9999	-10000	0	0
HDAC4/CaMK II delta B	0.027	0.005	-9999	-10000	0	0
Hsp90/HDAC6	0.038	0.022	-9999	-0.25	2	2
ESR1	0.012	0.077	-9999	-0.38	15	15
HDAC6/HDAC11	0.04	0.008	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.037	0.035	-9999	-10000	0	0
NPC	0.016	0.002	-9999	-10000	0	0
MEF2C	0.026	0.008	-9999	-10000	0	0
RAN	0.027	0.005	-9999	-10000	0	0
HDAC4/MEF2C	0.07	0.032	-9999	-10000	0	0
GNG2	0.027	0.019	-9999	-0.35	1	1
NCOR2	0.027	0.005	-9999	-10000	0	0
TUBB2A	0.025	0.021	-9999	-0.38	1	1
HDAC11	0.028	0.004	-9999	-10000	0	0
HSP90AA1	0.025	0.027	-9999	-0.35	2	2
RANBP2	0.028	0.003	-9999	-10000	0	0
ANKRA2	0.026	0.007	-9999	-10000	0	0
RFXANK	0.027	0.005	-9999	-10000	0	0
nuclear import	-0.027	0.017	-9999	-10000	0	0

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.033	0.017	-10000	0	-10000	0	0
ATM	0.026	0.02	-10000	0	-0.35	1	1
UBE2D3	0.027	0.005	-10000	0	-10000	0	0
PRKDC	0.025	0.009	-10000	0	-10000	0	0
ATR	0.027	0.006	-10000	0	-10000	0	0
UBE2L3	0.027	0.006	-10000	0	-10000	0	0
FANCD2	0.016	0.025	-10000	0	-10000	0	0
protein ubiquitination	0.051	0.054	-10000	0	-10000	0	0
XRCC5	0.028	0.004	-10000	0	-10000	0	0
XRCC6	0.027	0.006	-10000	0	-10000	0	0
M/R/N Complex	0.046	0.023	-10000	0	-10000	0	0
MRE11A	0.027	0.005	-10000	0	-10000	0	0
DNA-PK	0.048	0.021	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.022	0.06	-10000	0	-0.36	5	5
FANCF	0.027	0.005	-10000	0	-10000	0	0
BRCA1	0.027	0.019	-10000	0	-0.35	1	1
CCNE1	0.011	0.071	-10000	0	-0.35	15	15
CDK2/Cyclin E1	0.025	0.053	-10000	0	-0.25	14	14
FANCG	0.026	0.007	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.039	0.016	-10000	0	-0.25	1	1
FANCE	0.027	0.005	-10000	0	-10000	0	0
FANCC	0.027	0.006	-10000	0	-10000	0	0
NBN	0.025	0.01	-10000	0	-10000	0	0
FANCA	0.019	0.053	-10000	0	-0.35	8	8
DNA repair	0.028	0.066	0.24	11	-10000	0	11
BRCA1/BARD1/ubiquitin	0.039	0.016	-10000	0	-0.25	1	1
BARD1/DNA-PK	0.06	0.027	-10000	0	-10000	0	0
FANCL	0.027	0.019	-10000	0	-0.35	1	1
mRNA polyadenylation	-0.033	0.017	-10000	0	-10000	0	0
BRCA1/BARD1/CTIP/M/R/N Complex	0.027	0.043	-10000	0	-0.26	1	1
BRCA1/BACH1/BARD1/TopBP1	0.052	0.02	-10000	0	-0.21	1	1
BRCA1/BARD1/P53	0.062	0.028	-10000	0	-0.19	1	1
BARD1/CSTF1/BRCA1	0.044	0.027	-10000	0	-0.21	1	1
BRCA1/BACH1	0.027	0.019	-10000	0	-0.35	1	1
BARD1	0.028	0.004	-10000	0	-10000	0	0
PCNA	0.024	0.021	-10000	0	-0.35	1	1
BRCA1/BARD1/UbcH5C	0.053	0.019	-10000	0	-0.21	1	1
BRCA1/BARD1/UbcH7	0.052	0.02	-10000	0	-0.21	1	1
BRCA1/BARD1/RAD51/PCNA	0.06	0.034	-10000	0	-0.36	1	1
BARD1/DNA-PK/P53	0.066	0.035	-10000	0	-10000	0	0
BRCA1/BARD1/Ubiquitin	0.039	0.016	-10000	0	-0.25	1	1
BRCA1/BARD1/CTIP	0.038	0.024	-10000	0	-0.19	2	2
FA complex	0.024	0.031	-10000	0	-0.25	1	1
BARD1/EWS	0.039	0.01	-10000	0	-10000	0	0
RBBP8	0.011	0.014	-10000	0	-0.25	1	1
TP53	0.026	0.008	-10000	0	-10000	0	0
TOPBP1	0.027	0.005	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.059	0.028	0.19	1	-10000	0	1
BRCA1/BARD1	0.056	0.057	-10000	0	-10000	0	0
CSTF1	0.023	0.011	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.02	0.003	-10000	0	-10000	0	0
CDK2	0.027	0.006	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.027	0.005	-10000	0	-10000	0	0
RAD50	0.026	0.007	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.039	0.016	-10000	0	-0.25	1	1
EWSR1	0.027	0.006	-10000	0	-10000	0	0

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.025	0.022	-10000	0	-0.38	1	1
positive regulation of NF-kappaB transcription factor activity	0.03	0.037	-10000	0	-0.27	5	5
MAP2K4	0.025	0.035	-10000	0	-0.29	1	1
IKBKB	0.025	0.009	-10000	0	-10000	0	0
TNFRSF10B	0.024	0.021	-10000	0	-0.35	1	1
TNFRSF10A	0.025	0.009	-10000	0	-10000	0	0
SMPD1	0.011	0.012	-10000	0	-0.16	1	1
IKBKG	0.027	0.006	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.021	0.04	-10000	0	-0.38	4	4
TRAIL/TRAILR2	0.032	0.026	-10000	0	-0.26	2	2
TRAIL/TRAILR3	0.028	0.042	-10000	0	-0.25	8	8
TRAIL/TRAILR1	0.033	0.022	-10000	0	-0.27	1	1
TRAIL/TRAILR4	0.03	0.037	-10000	0	-0.27	5	5
TRAIL/TRAILR1/DAP3/GTP	0.042	0.025	-10000	0	-0.21	1	1
IKK complex	0.015	0.045	-10000	0	-0.34	1	1
RIPK1	0.026	0.007	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.02	0.004	-10000	0	-10000	0	0
MAPK3	0.012	0.015	-10000	0	-0.27	1	1
MAP3K1	0.024	0.035	-10000	0	-10000	0	0
TRAILR4 (trimer)	0.021	0.04	-10000	0	-0.38	4	4
TRADD	0.027	0.006	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.025	0.009	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.022	0.019	-10000	0	-10000	0	0
CFLAR	0.028	0.003	-10000	0	-10000	0	0
MAPK1	0.011	0.015	-10000	0	-0.27	1	1
TRAIL/TRAILR1/FADD/TRADD/RIP	0.058	0.041	-10000	0	-0.2	1	1
mol:ceramide	0.011	0.012	-10000	0	-0.16	1	1
FADD	0.026	0.007	-10000	0	-10000	0	0
MAPK8	0.025	0.047	0.2	1	-0.32	2	3
TRAF2	0.027	0.006	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.016	0.056	-10000	0	-0.35	9	9
CHUK	0.027	0.006	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	0.043	0.028	-10000	0	-0.23	1	1
DAP3	0.027	0.005	-10000	0	-10000	0	0
CASP10	0.024	0.051	0.2	3	-0.25	1	4
JNK cascade	0.03	0.037	-10000	0	-0.27	5	5
TRAIL (trimer)	0.025	0.022	-10000	0	-0.38	1	1
TNFRSF10C	0.016	0.056	-10000	0	-0.35	9	9
TRAIL/TRAILR1/DAP3/GTP/FADD	0.049	0.032	-10000	0	-0.2	1	1
TRAIL/TRAILR2/FADD	0.042	0.031	-10000	0	-0.22	2	2
cell death	0.011	0.012	-10000	0	-0.16	1	1
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.021	0.019	-10000	0	-0.19	1	1
TRAILR2 (trimer)	0.024	0.021	-10000	0	-0.35	1	1
CASP8	0.012	0.036	-10000	0	-0.61	1	1
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.057	0.042	-10000	0	-0.2	1	1

×

HIF-2-alpha transcription factor network

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
MMP14	0.025	0.11	-10000	0	-0.64	8	8
oxygen homeostasis	0.001	0.01	-10000	0	-10000	0	0
TCEB2	0.026	0.007	-10000	0	-10000	0	0
TCEB1	0.024	0.01	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	0.049	0.069	-10000	0	-10000	0	0
EPO	0.035	0.13	-10000	0	-0.54	1	1
FIH (dimer)	0.025	0.02	-10000	0	-10000	0	0
APEX1	0.024	0.023	-10000	0	-10000	0	0
SERPINE1	0.008	0.16	-10000	0	-0.51	2	2
FLT1	0.024	0.11	-10000	0	-0.55	10	10
ADORA2A	0.025	0.14	0.37	4	-0.55	1	5
germ cell development	0.02	0.14	-10000	0	-0.5	2	2
SLC11A2	0.027	0.14	-10000	0	-0.51	1	1
BHLHE40	0.029	0.14	-10000	0	-0.51	1	1
HIF1AN	0.025	0.02	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	0.037	0.1	0.25	1	-10000	0	1
ETS1	0.036	0.009	-10000	0	-10000	0	0
CITED2	0.02	0.12	-10000	0	-0.68	9	9
KDR	0.024	0.11	-10000	0	-0.57	8	8
PGK1	0.028	0.13	-10000	0	-0.51	1	1
SIRT1	0.027	0.006	-10000	0	-10000	0	0
response to hypoxia	0	0.002	-10000	0	-10000	0	0
HIF2A/ARNT	0.052	0.16	-10000	0	-0.58	1	1
EPAS1	0.019	0.06	-10000	0	-0.3	3	3
SP1	0.031	0.009	-10000	0	-10000	0	0
ABCG2	0.019	0.15	-10000	0	-0.52	6	6
EFNA1	0.029	0.14	-10000	0	-0.51	1	1
FXN	0.025	0.13	0.35	3	-0.54	1	4
POU5F1	0.02	0.15	-10000	0	-0.52	2	2
neuron apoptosis	-0.05	0.16	0.56	1	-10000	0	1
EP300	0.027	0.005	-10000	0	-10000	0	0
EGLN3	0.025	0.028	-10000	0	-0.39	1	1
EGLN2	0.025	0.019	-10000	0	-10000	0	0
EGLN1	0.025	0.019	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.046	0.023	-10000	0	-10000	0	0
VHL	0.028	0.004	-10000	0	-10000	0	0
ARNT	0.024	0.022	-10000	0	-10000	0	0
SLC2A1	0.015	0.15	0.37	4	-0.51	4	8
TWIST1	0.019	0.14	0.35	3	-10000	0	3
ELK1	0.031	0.01	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.043	0.1	-10000	0	-10000	0	0
VEGFA	0.03	0.13	-10000	0	-10000	0	0
CREBBP	0.026	0.007	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	0.043	0.071	-10000	0	-0.27	4	4
Ran/GTP/Exportin 1/HDAC1	-0.008	0.002	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.021	0.078	-10000	0	-0.32	6	6
SUMO1	0.028	0.003	-10000	0	-10000	0	0
ZFPM1	0.026	0.007	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.014	0.005	-10000	0	-10000	0	0
FKBP3	0.027	0.005	-10000	0	-10000	0	0
Histones	0.05	0.059	-10000	0	-0.29	1	1
YY1/LSF	0.017	0.055	-10000	0	-0.21	11	11
SMG5	0.027	0.005	-10000	0	-10000	0	0
RAN	0.027	0.005	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	0.018	0.036	-10000	0	-0.3	1	1
I kappa B alpha/HDAC1	0.027	0.046	-10000	0	-10000	0	0
SAP18	0.026	0.007	-10000	0	-10000	0	0
RELA	0.02	0.047	0.28	1	-0.36	2	3
HDAC1/Smad7	0.045	0.024	-10000	0	-10000	0	0
RANGAP1	0.027	0.005	-10000	0	-10000	0	0
HDAC3/TR2	0.026	0.052	-10000	0	-0.31	1	1
NuRD/MBD3 Complex	0.028	0.032	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.017	0.082	0.2	3	-0.33	10	13
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	0.022	0.045	-10000	0	-0.38	5	5
GATA1	0.02	0.049	-10000	0	-0.38	6	6
Mad/Max	0.04	0.009	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.019	0.073	-10000	0	-0.36	7	7
RBBP7	0.027	0.005	-10000	0	-10000	0	0
NPC	0.016	0.002	-10000	0	-10000	0	0
RBBP4	0.027	0.005	-10000	0	-10000	0	0
MAX	0.027	0.005	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.027	0.006	-10000	0	-10000	0	0
NFKBIA	0.016	0.027	-10000	0	-10000	0	0
KAT2B	0.024	0.041	-10000	0	-0.38	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.024	0.02	-10000	0	-0.28	1	1
SIN3 complex	0.061	0.027	-10000	0	-10000	0	0
SMURF1	0.025	0.009	-10000	0	-10000	0	0
CHD3	0.026	0.007	-10000	0	-10000	0	0
SAP30	0.026	0.007	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.026	0.008	-10000	0	-10000	0	0
YY1/HDAC3	0.013	0.054	-10000	0	-0.34	3	3
YY1/HDAC2	0.017	0.056	-10000	0	-0.28	2	2
YY1/HDAC1	0.018	0.056	-10000	0	-0.22	8	8
NuRD/MBD2 Complex (MeCP1)	0.024	0.036	-10000	0	-10000	0	0
PPARG	0.013	0.057	-10000	0	-0.28	8	8
HDAC8/hEST1B	0.052	0.016	-10000	0	-10000	0	0
UBE2I	0.026	0.007	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.027	0.006	-10000	0	-10000	0	0
TNFRSF1A	0.027	0.006	-10000	0	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.025	0.051	-10000	0	-0.31	1	1
MBD3L2	0.018	0.004	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.044	0.023	-10000	0	-10000	0	0
CREBBP	0.026	0.007	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.017	0.079	-10000	0	-0.35	10	10
HDAC1	0.027	0.005	-10000	0	-10000	0	0
HDAC3	0.016	0.032	-10000	0	-0.36	1	1
HDAC2	0.027	0.005	-10000	0	-10000	0	0
YY1	0.016	0.025	-10000	0	-0.22	4	4
HDAC8	0.027	0.005	-10000	0	-10000	0	0
SMAD7	0.025	0.009	-10000	0	-10000	0	0
NCOR2	0.027	0.005	-10000	0	-10000	0	0
MXD1	0.028	0.003	-10000	0	-10000	0	0
STAT3	0.02	0.007	-10000	0	-10000	0	0
NFKB1	0.027	0.005	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.028	0.003	-10000	0	-10000	0	0
YY1/LSF/HDAC1	0.032	0.055	-10000	0	-0.24	2	2
YY1/SAP30/HDAC1	0.031	0.056	-10000	0	-0.25	2	2
EP300	0.027	0.005	-10000	0	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.02	0.007	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.016	0.027	-10000	0	-10000	0	0
histone deacetylation	0.021	0.046	-10000	0	-0.24	5	5
STAT3 (dimer non-phopshorylated)/HDAC3	0.021	0.037	-10000	0	-0.38	1	1
nuclear export	-0.052	0.016	-10000	0	-10000	0	0
PRKACA	0.027	0.005	-10000	0	-10000	0	0
GATAD2B	0.027	0.005	-10000	0	-10000	0	0
GATAD2A	0.027	0.005	-10000	0	-10000	0	0
GATA2/HDAC3	0.022	0.058	-10000	0	-0.28	2	2
GATA1/HDAC1	0.034	0.038	-10000	0	-0.27	6	6
GATA1/HDAC3	0.021	0.058	-10000	0	-0.3	2	2
CHD4	0.027	0.006	-10000	0	-10000	0	0
TNF-alpha/TNFR1A	0.025	0.059	-10000	0	-0.25	17	17
SIN3/HDAC complex/Mad/Max	0.025	0.047	-10000	0	-0.41	2	2
NuRD Complex	0.014	0.081	-10000	0	-0.36	9	9
positive regulation of chromatin silencing	0.048	0.057	-10000	0	-0.28	1	1
SIN3B	0.027	0.005	-10000	0	-10000	0	0
MTA2	0.028	0.003	-10000	0	-10000	0	0
SIN3A	0.027	0.005	-10000	0	-10000	0	0
XPO1	0.028	0.003	-10000	0	-10000	0	0
SUMO1/HDAC1	0.036	0.034	-10000	0	-10000	0	0
HDAC complex	0.066	0.021	-10000	0	-10000	0	0
GATA1/Fog1	0.033	0.039	-10000	0	-0.27	6	6
FKBP25/HDAC1/HDAC2	0.053	0.015	-10000	0	-10000	0	0
TNF	0.01	0.08	-10000	0	-0.36	18	18
negative regulation of cell growth	0.024	0.052	-10000	0	-0.3	5	5
NuRD/MBD2/PRMT5 Complex	0.024	0.036	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.037	0.035	-10000	0	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.006	0.067	-10000	0	-0.29	11	11
SIN3/HDAC complex/NCoR1	0.012	0.059	-10000	0	-0.31	6	6
TFCP2	0.027	0.005	-10000	0	-10000	0	0
NR2C1	0.028	0.004	-10000	0	-10000	0	0
MBD3	0.026	0.007	-10000	0	-10000	0	0
MBD2	0.024	0.01	-10000	0	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.027	0.006	-9999	-10000	0	0
Rac1/GDP	0.025	0.011	-9999	-10000	0	0
DOCK1	0.027	0.006	-9999	-10000	0	0
ITGA4	0.025	0.033	-9999	-0.35	3	3
RAC1	0.026	0.008	-9999	-10000	0	0
alpha4/beta7 Integrin	0.036	0.03	-9999	-0.25	4	4
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.026	0.008	-9999	-10000	0	0
alpha4/beta1 Integrin	0.049	0.031	-9999	-0.21	4	4
alpha4/beta7 Integrin/Paxillin	0.041	0.027	-9999	-0.19	4	4
lamellipodium assembly	0.006	0.092	-9999	-0.37	18	18
PIK3CA	0.026	0.007	-9999	-10000	0	0
PI3K	0.036	0.014	-9999	-10000	0	0
ARF6	0.027	0.006	-9999	-10000	0	0
TLN1	0.026	0.008	-9999	-10000	0	0
PXN	0.013	0.003	-9999	-10000	0	0
PIK3R1	0.026	0.008	-9999	-10000	0	0
ARF6/GTP	0.05	0.031	-9999	-10000	0	0
cell adhesion	0.048	0.032	-9999	-10000	0	0
CRKL/CBL	0.038	0.012	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.04	0.027	-9999	-0.19	4	4
ITGB1	0.026	0.02	-9999	-0.35	1	1
ITGB7	0.026	0.021	-9999	-0.38	1	1
ARF6/GDP	0.025	0.01	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.051	0.037	-9999	-10000	0	0
p130Cas/Crk/Dock1	0.048	0.021	-9999	-10000	0	0
VCAM1	0.025	0.033	-9999	-0.35	3	3
alpha4/beta1 Integrin/Paxillin/Talin	0.05	0.033	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.053	0.031	-9999	-10000	0	0
BCAR1	0.027	0.006	-9999	-10000	0	0
mol:GDP	-0.051	0.031	-9999	-10000	0	0
CBL	0.027	0.006	-9999	-10000	0	0
PRKACA	0.027	0.005	-9999	-10000	0	0
GIT1	0.028	0.004	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.05	0.033	-9999	-10000	0	0
Rac1/GTP	0.005	0.1	-9999	-0.41	18	18

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.038	0.012	-10000	0	-10000	0	0
FBXW11	0.027	0.006	-10000	0	-10000	0	0
NF kappa B1 p50/c-Rel	0.027	0.011	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.036	0.052	0.22	5	-0.3	1	6
NFKBIA	0.024	0.041	-10000	0	-10000	0	0
MAPK14	0.027	0.006	-10000	0	-10000	0	0
NF kappa B1 p105/p50	0.026	0.011	-10000	0	-10000	0	0
ARRB2	0.013	0.005	-10000	0	-10000	0	0
REL	0.028	0.003	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	0.026	0.012	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	0.026	0.011	-10000	0	-10000	0	0
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
NF kappa B1 p50 dimer	0.019	0.008	-10000	0	-10000	0	0
PIK3R1	0.026	0.008	-10000	0	-10000	0	0
NFKB1	0.012	0.005	-10000	0	-10000	0	0
RELA	0.027	0.005	-10000	0	-10000	0	0
positive regulation of anti-apoptosis	0.021	0.041	-10000	0	-0.31	1	1
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.035	0.054	0.2	5	-0.29	2	7
SRC	0.024	0.01	-10000	0	-10000	0	0
PI3K	0.036	0.014	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.021	0.041	-10000	0	-0.31	1	1
IKBKB	0.025	0.009	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.027	0.006	-10000	0	-10000	0	0
SYK	0.026	0.021	-10000	0	-0.38	1	1
I kappa B alpha/PIK3R1	0.034	0.052	0.21	4	-0.26	2	6
cell death	0.032	0.05	0.18	3	-0.28	2	5
NF kappa B1 p105/c-Rel	0.027	0.011	-10000	0	-10000	0	0
LCK	0.017	0.062	-10000	0	-0.35	11	11
BCL3	0.027	0.007	-10000	0	-10000	0	0

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.026	0.049	0.15	54	-10000	0	54
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.018	0.032	0.17	7	-0.17	1	8
AP2	0.037	0.013	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.034	0.013	-10000	0	-10000	0	0
CLTB	0.027	0.006	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.018	0.008	-10000	0	-10000	0	0
CD4	0.025	0.027	-10000	0	-0.35	2	2
CLTA	0.025	0.008	-10000	0	-10000	0	0
mol:GTP	-0.001	0.002	-10000	0	-10000	0	0
ARFGAP1	0.006	0.003	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.008	0.011	-10000	0	-10000	0	0
ARF1/GTP	0.032	0.014	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.009	0.006	-10000	0	-10000	0	0
mol:Choline	0.007	0.011	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.028	0.007	-10000	0	-10000	0	0
DDEF1	0.006	0.012	-10000	0	-10000	0	0
ARF1/GDP	0.005	0.01	-10000	0	-10000	0	0
AP2M1	0.026	0.007	-10000	0	-10000	0	0
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	0.012	0.006	-10000	0	-10000	0	0
Rac/GTP	0.02	0.007	-10000	0	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.032	0.018	-10000	0	-10000	0	0
ARFIP2	0.022	0.015	-10000	0	-10000	0	0
COPA	0.027	0.005	-10000	0	-10000	0	0
RAC1	0.026	0.008	-10000	0	-10000	0	0
ARF1/GTP/coatomer protein complex	0.014	0.038	0.14	4	-0.19	4	8
ARF1/GTP/ARHGAP10	0.018	0.007	-10000	0	-10000	0	0
GGA3	0.027	0.005	-10000	0	-10000	0	0
ARF1/GTP/Membrin	0.026	0.012	-10000	0	-10000	0	0
AP2A1	0.027	0.006	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.011	0.023	-10000	0	-0.2	3	3
ARF1/GDP/Membrin	0.026	0.016	-10000	0	-10000	0	0
Arfaptin 2/Rac/GDP	0.033	0.013	-10000	0	-10000	0	0
CYTH2	0.028	0.007	-10000	0	-10000	0	0
ARF1/GTP/GGA3	0.036	0.011	-10000	0	-10000	0	0
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.019	0.006	-10000	0	-10000	0	0
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	0.021	0.025	-10000	0	-10000	0	0
PLD2	0.007	0.012	-10000	0	-10000	0	0
ARF-GAP1/v-SNARE	0.006	0.003	-10000	0	-10000	0	0
PIP5K1A	0.008	0.011	-10000	0	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0.019	0.023	-10000	0	-10000	0	0
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.007	0.011	-10000	0	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	0.006	0.003	-10000	0	-10000	0	0
GOSR2	0.013	0.008	-10000	0	-10000	0	0
USO1	0.011	0.028	-10000	0	-0.31	3	3
GBF1	0.009	0.036	-10000	0	-0.31	5	5
ARF1/GTP/Arfaptin 2	0.037	0.012	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.048	0.027	-10000	0	-0.21	2	2

×

Regulation of cytoplasmic and nuclear SMAD2/3 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.024	0.01	-10000	0	-10000	0	0
SMAD2	0.011	0.038	0.19	2	-10000	0	2
SMAD3	0.025	0.025	-10000	0	-10000	0	0
SMAD3/SMAD4	0.022	0.086	-10000	0	-0.42	12	12
SMAD4/Ubc9/PIASy	0.045	0.023	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.047	0.046	-10000	0	-10000	0	0
PPM1A	0.027	0.005	-10000	0	-10000	0	0
CALM1	0.027	0.005	-10000	0	-10000	0	0
SMAD2/SMAD4	0.017	0.033	-10000	0	-0.23	1	1
MAP3K1	0.026	0.008	-10000	0	-10000	0	0
TRAP-1/SMAD4	0.035	0.015	-10000	0	-10000	0	0
MAPK3	0.027	0.005	-10000	0	-10000	0	0
MAPK1	0.027	0.006	-10000	0	-10000	0	0
NUP214	0.027	0.005	-10000	0	-10000	0	0
CTDSP1	0.028	0.004	-10000	0	-10000	0	0
CTDSP2	0.027	0.006	-10000	0	-10000	0	0
CTDSPL	0.027	0.005	-10000	0	-10000	0	0
KPNB1	0.028	0.002	-10000	0	-10000	0	0
TGFBRAP1	0.028	0.004	-10000	0	-10000	0	0
UBE2I	0.026	0.007	-10000	0	-10000	0	0
NUP153	0.027	0.006	-10000	0	-10000	0	0
KPNA2	0.027	0.019	-10000	0	-0.35	1	1
PIAS4	0.026	0.007	-10000	0	-10000	0	0

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.049	0.025	-10000	0	-10000	0	0
CLOCK	0.029	0.006	-10000	0	-10000	0	0
TIMELESS/CRY2	0.037	0.022	-10000	0	-10000	0	0
DEC1/BMAL1	0.034	0.022	-10000	0	-0.26	2	2
ATR	0.027	0.006	-10000	0	-10000	0	0
NR1D1	0.019	0.014	-10000	0	-10000	0	0
ARNTL	0.028	0.021	-10000	0	-0.38	1	1
TIMELESS	0.021	0.012	-10000	0	-10000	0	0
NPAS2	0.029	0.005	-10000	0	-10000	0	0
CRY2	0.027	0.006	-10000	0	-10000	0	0
mol:CO	-0.008	0.004	0.074	1	-10000	0	1
CHEK1	0.026	0.02	-10000	0	-0.35	1	1
mol:HEME	0.008	0.004	-10000	0	-0.074	1	1
PER1	0.018	0.057	-10000	0	-0.38	8	8
BMAL/CLOCK/NPAS2	0.062	0.023	-10000	0	-0.22	1	1
BMAL1/CLOCK	0.028	0.053	-10000	0	-10000	0	0
S phase of mitotic cell cycle	0.049	0.025	-10000	0	-10000	0	0
TIMELESS/CHEK1/ATR	0.05	0.025	-10000	0	-10000	0	0
mol:NADPH	0.008	0.004	-10000	0	-0.074	1	1
PER1/TIMELESS	0.033	0.035	-10000	0	-10000	0	0
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.018	0.019	-10000	0	-0.35	1	1

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.027	0.005	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0.005	0.011	-10000	0	-10000	0	0
MDM2/SUMO1	0.035	0.036	-10000	0	-10000	0	0
HDAC4	0.027	0.005	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	0.005	0.01	-10000	0	-10000	0	0
SUMO1	0.028	0.003	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1	0.012	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
XPO1	0.009	0.009	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
RAN	0.027	0.005	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.028	0.003	-10000	0	-10000	0	0
SUMO1/HDAC4	0.036	0.035	-10000	0	-10000	0	0
SUMO1/HDAC1	0.036	0.034	-10000	0	-10000	0	0
RANGAP1	0.027	0.005	-10000	0	-10000	0	0
MDM2/SUMO1/SUMO1	0.059	0.033	-10000	0	-0.19	2	2
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.014	0.005	-10000	0	-10000	0	0
Ran/GTP	0.025	0.03	-10000	0	-0.16	2	2
EntrezGene:23225	0	0	-10000	0	-10000	0	0
MDM2	0.025	0.027	-10000	0	-0.35	2	2
UBE2I	0.026	0.007	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.024	0.034	0.19	4	-10000	0	4
NPC	0.016	0.002	-10000	0	-10000	0	0
PIAS2	0.025	0.009	-10000	0	-10000	0	0
PIAS1	0.027	0.005	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.039	0.01	-9999	-10000	0	0
FBXW11	0.027	0.006	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.027	0.006	-9999	-10000	0	0
CHUK	0.027	0.006	-9999	-10000	0	0
NF kappa B2 p100/RelB	0.072	0.032	-9999	-10000	0	0
NFKB1	0.027	0.005	-9999	-10000	0	0
MAP3K14	0.028	0.004	-9999	-10000	0	0
NF kappa B1 p50/RelB	0.038	0.018	-9999	-0.25	1	1
RELB	0.026	0.02	-9999	-0.35	1	1
NFKB2	0.027	0.006	-9999	-10000	0	0
NF kappa B2 p52/RelB	0.034	0.016	-9999	-0.2	1	1
regulation of B cell activation	0.034	0.016	-9999	-0.2	1	1

pid_entity	TCGA.ZQ.A9CR	TCGA.ZA.A8F6	TCGA.VQ.AA6K	TCGA.VQ.AA6J
109_MAP3K5	0.031	0.031	0.078	0.0026
47_PPARGC1A	0.028	0.028	0.028	0.028
105_BMP4	0.028	0.028	0.028	0.028
105_BMP6	0.028	0.028	0.028	0.028
105_BMP7	0.028	0.028	0	0.028
105_BMP2	0.028	0.028	0.028	0.028
131_RELN/VLDLR	-0.38	0.073	0.073	-0.38
30_TGFB1/TGF beta receptor Type II	0.028	0.028	0.032	0.031
84_STAT5B	-0.04	0.0014	0.038	0.053
84_STAT5A	-0.04	0.0014	0.038	0.053