PARADIGM pathway analysis of mRNASeq expression data - Uterine Corpus Endometrioid Carcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
FOXM1 transcription factor network	183
Aurora B signaling	160
HIF-1-alpha transcription factor network	125
Signaling events regulated by Ret tyrosine kinase	120
Endothelins	107
Angiopoietin receptor Tie2-mediated signaling	105
p75(NTR)-mediated signaling	91
PDGFR-alpha signaling pathway	91
Signaling events mediated by the Hedgehog family	89
Integrins in angiogenesis	80

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
FOXM1 transcription factor network	0.3401	183	9338	51	-0.97	0.011	1000	-1000	-0.14	-1000
Aurora B signaling	0.2974	160	10732	67	-0.52	0.011	1000	-1000	-0.038	-1000
HIF-1-alpha transcription factor network	0.2323	125	9515	76	-0.49	0.017	1000	-1000	-0.065	-1000
Signaling events regulated by Ret tyrosine kinase	0.2230	120	9865	82	-0.19	0.011	1000	-1000	-0.047	-1000
Endothelins	0.1989	107	10300	96	-0.34	0.011	1000	-1000	-0.046	-1000
Angiopoietin receptor Tie2-mediated signaling	0.1952	105	9284	88	-0.32	0.043	1000	-1000	-0.074	-1000
p75(NTR)-mediated signaling	0.1691	91	11418	125	-0.2	0.03	1000	-1000	-0.055	-1000
PDGFR-alpha signaling pathway	0.1691	91	4047	44	-0.29	0.025	1000	-1000	-0.033	-1000
Signaling events mediated by the Hedgehog family	0.1654	89	4633	52	-0.26	0.14	1000	-1000	-0.018	-1000
Integrins in angiogenesis	0.1487	80	6795	84	-0.29	0.024	1000	-1000	-0.05	-1000
Cellular roles of Anthrax toxin	0.1301	70	2747	39	-0.13	0.019	1000	-1000	-0.013	-1000
S1P3 pathway	0.1283	69	2909	42	-0.41	0.016	1000	-1000	-0.025	-1000
Aurora C signaling	0.1264	68	478	7	-0.29	0.009	1000	-1000	-0.017	-1000
Nongenotropic Androgen signaling	0.1264	68	3581	52	-0.22	0.11	1000	-1000	-0.032	-1000
Wnt signaling	0.1134	61	427	7	-0.089	-0.002	1000	-1000	-0.014	-1000
PLK1 signaling events	0.1059	57	4868	85	-0.3	0.044	1000	-1000	-0.031	-1000
Signaling mediated by p38-alpha and p38-beta	0.1059	57	2548	44	-0.08	0.011	1000	-1000	-0.031	-1000
Reelin signaling pathway	0.1041	56	3165	56	-0.15	0.03	1000	-1000	-0.043	-1000
Effects of Botulinum toxin	0.1022	55	1450	26	-0.11	0.018	1000	-1000	-0.034	-1000
LPA4-mediated signaling events	0.1004	54	653	12	-0.12	0.015	1000	-1000	-0.007	-1000
Glypican 1 network	0.1004	54	2626	48	-0.22	0.022	1000	-1000	-0.012	-1000
IGF1 pathway	0.0929	50	2852	57	-0.076	0.022	1000	-1000	-0.048	-1000
Aurora A signaling	0.0911	49	2974	60	-0.25	0.022	1000	-1000	-0.017	-1000
Fc-epsilon receptor I signaling in mast cells	0.0911	49	4802	97	-0.12	0.028	1000	-1000	-0.046	-1000
S1P4 pathway	0.0911	49	1237	25	-0.1	0.024	1000	-1000	-0.013	-1000
S1P5 pathway	0.0874	47	801	17	-0.1	0.032	1000	-1000	-0.013	-1000
Noncanonical Wnt signaling pathway	0.0855	46	1197	26	-0.14	0.011	1000	-1000	-0.025	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0855	46	3159	68	-0.2	0.08	1000	-1000	-0.082	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0855	46	5574	120	-0.19	0.14	1000	-1000	-0.043	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0855	46	3646	78	-0.099	0.043	1000	-1000	-0.035	-1000
TCGA08_retinoblastoma	0.0836	45	365	8	-0.14	0.024	1000	-1000	-0.009	-1000
Thromboxane A2 receptor signaling	0.0818	44	4702	105	-0.18	0.031	1000	-1000	-0.039	-1000
BMP receptor signaling	0.0781	42	3417	81	-0.28	0.038	1000	-1000	-0.041	-1000
Plasma membrane estrogen receptor signaling	0.0781	42	3679	86	-0.15	0.066	1000	-1000	-0.042	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0762	41	1420	34	-0.039	0.011	1000	-1000	-0.014	-1000
Syndecan-1-mediated signaling events	0.0762	41	1411	34	-0.17	0.011	1000	-1000	-0.02	-1000
amb2 Integrin signaling	0.0762	41	3427	82	-0.15	0.022	1000	-1000	-0.045	-1000
Ephrin A reverse signaling	0.0706	38	267	7	-0.023	0	1000	-1000	-0.01	-1000
FOXA2 and FOXA3 transcription factor networks	0.0706	38	1764	46	-0.22	0.016	1000	-1000	-0.062	-1000
S1P1 pathway	0.0706	38	1375	36	-0.12	0.011	1000	-1000	-0.031	-1000
Ras signaling in the CD4+ TCR pathway	0.0706	38	658	17	-0.077	0.015	1000	-1000	-0.019	-1000
Osteopontin-mediated events	0.0632	34	1314	38	-0.12	0.014	1000	-1000	-0.053	-1000
Ephrin B reverse signaling	0.0613	33	1600	48	-0.095	0.015	1000	-1000	-0.04	-1000
TCGA08_p53	0.0595	32	228	7	-0.089	0.047	1000	-1000	-0.007	-1000
LPA receptor mediated events	0.0576	31	3235	102	-0.14	0.029	1000	-1000	-0.055	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0558	30	2611	85	-0.21	0.012	1000	-1000	-0.034	-1000
Glypican 2 network	0.0558	30	120	4	-0.014	-0.001	1000	-1000	-0.006	-1000
IL4-mediated signaling events	0.0539	29	2727	91	-0.52	0.26	1000	-1000	-0.13	-1000
FAS signaling pathway (CD95)	0.0539	29	1406	47	-0.075	0.037	1000	-1000	-0.025	-1000
EGFR-dependent Endothelin signaling events	0.0539	29	616	21	-0.11	0.02	1000	-1000	-0.042	-1000
Arf6 signaling events	0.0520	28	1747	62	-0.087	0.027	1000	-1000	-0.028	-1000
Visual signal transduction: Rods	0.0520	28	1504	52	-0.11	0.011	1000	-1000	-0.046	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0502	27	1490	54	-0.14	0.022	1000	-1000	-0.05	-1000
Syndecan-4-mediated signaling events	0.0502	27	1826	67	-0.26	0.016	1000	-1000	-0.051	-1000
Visual signal transduction: Cones	0.0483	26	994	38	-0.081	0.011	1000	-1000	-0.03	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0483	26	1379	52	-0.079	0.023	1000	-1000	-0.034	-1000
Coregulation of Androgen receptor activity	0.0465	25	1964	76	-0.13	0.022	1000	-1000	-0.021	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0446	24	3019	125	-0.067	0.029	1000	-1000	-0.054	-1000
Hedgehog signaling events mediated by Gli proteins	0.0428	23	1539	65	-0.1	0.038	1000	-1000	-0.037	-1000
Syndecan-2-mediated signaling events	0.0409	22	1532	69	-0.1	0.028	1000	-1000	-0.011	-1000
Presenilin action in Notch and Wnt signaling	0.0409	22	1346	61	-0.12	0.031	1000	-1000	-0.043	-1000
Glucocorticoid receptor regulatory network	0.0409	22	2513	114	-0.24	0.046	1000	-1000	-0.046	-1000
Calcium signaling in the CD4+ TCR pathway	0.0409	22	708	31	-0.12	0.015	1000	-1000	-0.047	-1000
TCGA08_rtk_signaling	0.0409	22	594	26	-0.15	0.023	1000	-1000	-0.011	-1000
IL2 signaling events mediated by STAT5	0.0409	22	488	22	-0.1	0.056	1000	-1000	-0.028	-1000
BCR signaling pathway	0.0409	22	2205	99	-0.06	0.047	1000	-1000	-0.047	-1000
Insulin Pathway	0.0390	21	1557	74	-0.13	0.03	1000	-1000	-0.049	-1000
Regulation of Androgen receptor activity	0.0390	21	1536	70	-0.22	0.023	1000	-1000	-0.048	-1000
IL6-mediated signaling events	0.0372	20	1553	75	-0.12	0.062	1000	-1000	-0.043	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0372	20	665	33	-0.16	0.034	1000	-1000	-0.025	-1000
Retinoic acid receptors-mediated signaling	0.0353	19	1105	58	-0.052	0.022	1000	-1000	-0.043	-1000
Regulation of nuclear SMAD2/3 signaling	0.0335	18	2472	136	-0.16	0.054	1000	-1000	-0.034	-1000
Signaling events mediated by PTP1B	0.0335	18	1390	76	-0.12	0.024	1000	-1000	-0.045	-1000
Nectin adhesion pathway	0.0335	18	1180	63	-0.067	0.021	1000	-1000	-0.04	-1000
Canonical Wnt signaling pathway	0.0335	18	932	51	-0.097	0.05	1000	-1000	-0.031	-1000
Regulation of p38-alpha and p38-beta	0.0335	18	993	54	-0.18	0.043	1000	-1000	-0.036	-1000
Rapid glucocorticoid signaling	0.0335	18	374	20	-0.051	0.011	1000	-1000	-0.007	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0316	17	501	28	-0.1	0.032	1000	-1000	-0.017	-1000
BARD1 signaling events	0.0297	16	967	57	-0.13	0.028	1000	-1000	-0.033	-1000
Class I PI3K signaling events mediated by Akt	0.0297	16	1138	68	-0.24	0.04	1000	-1000	-0.021	-1000
Signaling mediated by p38-gamma and p38-delta	0.0297	16	240	15	-0.017	0.021	1000	-1000	-0.014	-1000
Regulation of Telomerase	0.0297	16	1664	102	-0.3	0.038	1000	-1000	-0.052	-1000
IL12-mediated signaling events	0.0279	15	1314	87	-0.3	0.045	1000	-1000	-0.094	-1000
IL1-mediated signaling events	0.0260	14	900	62	-0.038	0.04	1000	-1000	-0.05	-1000
TCR signaling in naïve CD8+ T cells	0.0260	14	1338	93	-0.044	0.04	1000	-1000	-0.046	-1000
EPHB forward signaling	0.0260	14	1264	85	-0.034	0.03	1000	-1000	-0.051	-1000
Signaling events mediated by PRL	0.0260	14	479	34	-0.13	0.018	1000	-1000	-0.015	-1000
IFN-gamma pathway	0.0242	13	923	68	-0.23	0.048	1000	-1000	-0.051	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0242	13	1127	83	-0.24	0.044	1000	-1000	-0.043	-1000
FoxO family signaling	0.0242	13	884	64	-0.24	0.042	1000	-1000	-0.045	-1000
ErbB4 signaling events	0.0223	12	838	69	-0.072	0.03	1000	-1000	-0.056	-1000
Insulin-mediated glucose transport	0.0223	12	407	32	-0.24	0.025	1000	-1000	-0.03	-1000
Syndecan-3-mediated signaling events	0.0223	12	427	35	-0.089	0.03	1000	-1000	-0.023	-1000
PDGFR-beta signaling pathway	0.0223	12	1256	97	-0.021	0.039	1000	-1000	-0.043	-1000
EPO signaling pathway	0.0204	11	612	55	-0.025	0.035	1000	-1000	-0.045	-1000
mTOR signaling pathway	0.0204	11	627	53	-0.026	0.018	1000	-1000	-0.036	-1000
HIF-2-alpha transcription factor network	0.0204	11	498	43	-0.14	0.022	1000	-1000	-0.049	-1000
IL2 signaling events mediated by PI3K	0.0204	11	681	58	-0.11	0.043	1000	-1000	-0.053	-1000
Class IB PI3K non-lipid kinase events	0.0204	11	33	3	-0.003	0.003	1000	-1000	-0.007	-1000
ErbB2/ErbB3 signaling events	0.0186	10	672	65	-0.12	0.022	1000	-1000	-0.039	-1000
Signaling events mediated by HDAC Class III	0.0186	10	407	40	-0.078	0.016	1000	-1000	-0.021	-1000
JNK signaling in the CD4+ TCR pathway	0.0167	9	166	17	-0.014	0.034	1000	-1000	-0.019	-1000
Ceramide signaling pathway	0.0149	8	615	76	-0.068	0.036	1000	-1000	-0.023	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0149	8	328	37	-0.02	0.027	1000	-1000	-0.026	-1000
ceramide signaling pathway	0.0149	8	403	49	-0.031	0.038	1000	-1000	-0.016	-1000
IL27-mediated signaling events	0.0149	8	409	51	-0.053	0.014	1000	-1000	-0.059	-1000
Caspase cascade in apoptosis	0.0130	7	543	74	-0.032	0.035	1000	-1000	-0.018	-1000
Signaling events mediated by HDAC Class II	0.0130	7	533	75	-0.051	0.029	1000	-1000	-0.025	-1000
IL23-mediated signaling events	0.0130	7	444	60	-0.047	0.043	1000	-1000	-0.12	-1000
p38 MAPK signaling pathway	0.0130	7	324	44	-0.046	0.028	1000	-1000	-0.036	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0112	6	270	45	-0.032	0.057	1000	-1000	-0.048	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0093	5	373	74	-0.075	0.062	1000	-1000	-0.05	-1000
Canonical NF-kappaB pathway	0.0074	4	176	39	-0.032	0.058	1000	-1000	-0.048	-1000
PLK2 and PLK4 events	0.0074	4	12	3	0.008	0.015	1000	-1000	-0.008	-1000
TRAIL signaling pathway	0.0074	4	198	48	-0.001	0.037	1000	-1000	-0.041	-1000
Class I PI3K signaling events	0.0074	4	316	73	-0.015	0.053	1000	-1000	-0.034	-1000
Arf6 trafficking events	0.0074	4	351	71	-0.19	0.035	1000	-1000	-0.041	-1000
Signaling events mediated by HDAC Class I	0.0056	3	377	104	-0.032	0.044	1000	-1000	-0.034	-1000
Paxillin-dependent events mediated by a4b1	0.0056	3	143	36	-0.031	0.032	1000	-1000	-0.039	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0037	2	46	23	-0.004	0.036	1000	-1000	-0.018	-1000
a4b1 and a4b7 Integrin signaling	0.0037	2	11	5	0.009	0.015	1000	-1000	-0.008	-1000
VEGFR1 specific signals	0.0037	2	138	56	-0.062	0.052	1000	-1000	-0.025	-1000
Arf6 downstream pathway	0.0019	1	50	43	-0.023	0.023	1000	-1000	-0.021	-1000
Atypical NF-kappaB pathway	0.0019	1	36	31	0	0.04	1000	-1000	-0.017	-1000
E-cadherin signaling in the nascent adherens junction	0.0019	1	95	76	-0.003	0.048	1000	-1000	-0.047	-1000
E-cadherin signaling in keratinocytes	0.0019	1	80	43	-0.034	0.037	1000	-1000	-0.036	-1000
E-cadherin signaling events	0.0019	1	7	5	0.009	0.021	1000	-1000	-0.011	-1000
Circadian rhythm pathway	0.0000	0	15	22	-0.011	0.04	1000	-1000	-0.025	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	0	27	0	0.028	1000	-1000	-0.032	-1000
Arf1 pathway	0.0000	0	8	54	0	0.028	1000	-1000	-0.018	-1000
Alternative NF-kappaB pathway	0.0000	0	2	13	0	0.033	1000	-1000	-0.013	-1000
Total	NA	4001	238234	7203	-17	4.3	131000	-131000	-4.7	-131000

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.63	0.36	-9999	-0.99	208	208
PLK1	-0.15	0.088	-9999	-10000	0	0
BIRC5	-0.16	0.082	-9999	-10000	0	0
HSPA1B	-0.63	0.36	-9999	-0.98	212	212
MAP2K1	-0.021	0.016	-9999	-10000	0	0
BRCA2	-0.63	0.36	-9999	-0.99	208	208
FOXM1	-0.76	0.48	-9999	-1.1	286	286
XRCC1	-0.63	0.36	-9999	-0.96	229	229
FOXM1B/p19	-0.68	0.4	-9999	-0.95	307	307
Cyclin D1/CDK4	-0.58	0.32	-9999	-0.87	244	244
CDC2	-0.67	0.38	-9999	-0.96	285	285
TGFA	-0.57	0.31	-9999	-0.86	229	229
SKP2	-0.63	0.36	-9999	-0.95	242	242
CCNE1	-0.14	0.17	-9999	-0.34	217	217
CKS1B	-0.63	0.36	-9999	-0.95	238	238
RB1	-0.24	0.12	-9999	-0.53	11	11
FOXM1C/SP1	-0.7	0.42	-9999	-1	282	282
AURKB	-0.18	0.068	-9999	-10000	0	0
CENPF	-0.67	0.38	-9999	-0.97	275	275
CDK4	-0.001	0.005	-9999	-10000	0	0
MYC	-0.56	0.32	-9999	-0.84	244	244
CHEK2	-0.022	0.022	-9999	-0.35	1	1
ONECUT1	-0.62	0.35	-9999	-0.9	268	268
CDKN2A	-0.13	0.17	-9999	-0.32	225	225
LAMA4	-0.66	0.4	-9999	-1	244	244
FOXM1B/HNF6	-0.7	0.42	-9999	-1	270	270
FOS	-0.77	0.48	-9999	-1.1	286	286
SP1	0.011	0.001	-9999	-10000	0	0
CDC25B	-0.63	0.36	-9999	-0.95	242	242
response to radiation	-0.03	0.014	-9999	-10000	0	0
CENPB	-0.63	0.36	-9999	-0.95	243	243
CENPA	-0.69	0.38	-9999	-0.98	282	282
NEK2	-0.69	0.37	-9999	-0.98	281	281
HIST1H2BA	-0.64	0.36	-9999	-0.95	249	249
CCNA2	-0.07	0.14	-9999	-0.34	114	114
EP300	0.011	0	-9999	-10000	0	0
CCNB1/CDK1	-0.72	0.43	-9999	-1.1	260	260
CCNB2	-0.69	0.38	-9999	-0.99	273	273
CCNB1	-0.67	0.39	-9999	-1	254	254
ETV5	-0.63	0.36	-9999	-0.97	228	228
ESR1	-0.68	0.41	-9999	-1	247	247
CCND1	-0.59	0.33	-9999	-0.88	248	248
GSK3A	-0.014	0.013	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	-0.12	0.14	-9999	-0.25	261	261
CDK2	0.003	0.004	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.038	0.017	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.67	0.39	-9999	-0.95	303	303
GAS1	-0.97	0.48	-9999	-1.3	375	375
MMP2	-0.64	0.38	-9999	-1	206	206
RB1/FOXM1C	-0.62	0.36	-9999	-0.93	259	259
CREBBP	0.009	0.026	-9999	-0.41	2	2

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.12	0.064	-9999	-10000	0	0
STMN1	-0.18	0.076	-9999	-0.21	472	472
Aurora B/RasGAP/Survivin	-0.27	0.12	-9999	-0.34	403	403
Chromosomal passenger complex/Cul3 protein complex	-0.12	0.092	-9999	-0.29	91	91
BIRC5	-0.26	0.14	-9999	-0.33	416	416
DES	-0.52	0.25	-9999	-0.63	448	448
Aurora C/Aurora B/INCENP	-0.13	0.062	-9999	-0.31	3	3
Aurora B/TACC1	-0.19	0.11	-9999	-0.22	481	481
Aurora B/PP2A	-0.18	0.077	-9999	-0.21	472	472
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.024	0.014	-9999	-10000	0	0
mitotic metaphase/anaphase transition	-0.004	0.003	-9999	-10000	0	0
NDC80	-0.2	0.097	-9999	-0.23	473	473
Cul3 protein complex	-0.026	0.099	-9999	-0.23	103	103
KIF2C	-0.067	0.035	-9999	-10000	0	0
PEBP1	0.002	0.004	-9999	-10000	0	0
KIF20A	-0.3	0.1	-9999	-0.33	485	485
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.18	0.082	-9999	-0.21	472	472
SEPT1	0.01	0.018	-9999	-0.41	1	1
SMC2	0.01	0.015	-9999	-0.33	1	1
SMC4	0.011	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.01	0.015	-9999	-10000	0	0
PSMA3	0.011	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.004	0.002	-9999	-10000	0	0
H3F3B	-0.074	0.034	-9999	-10000	0	0
AURKB	-0.28	0.12	-9999	-0.33	472	472
AURKC	0.009	0.025	-9999	-0.33	3	3
CDCA8	-0.19	0.17	-9999	-0.34	312	312
cytokinesis	-0.15	0.069	-9999	-0.25	19	19
Aurora B/Septin1	-0.13	0.079	-9999	-0.24	18	18
AURKA	-0.091	0.16	-9999	-0.33	159	159
INCENP	0.004	0.004	-9999	-10000	0	0
KLHL13	-0.07	0.16	-9999	-0.41	103	103
BUB1	-0.26	0.14	-9999	-0.33	422	422
hSgo1/Aurora B/Survivin	-0.37	0.15	-9999	-0.43	459	459
EVI5	0.011	0.001	-9999	-10000	0	0
RhoA/GTP	-0.11	0.065	-9999	-0.28	23	23
SGOL1	-0.25	0.14	-9999	-0.33	418	418
CENPA	-0.1	0.051	-9999	-0.15	152	152
NCAPG	-0.22	0.16	-9999	-0.33	358	358
Aurora B/HC8 Proteasome	-0.18	0.077	-9999	-0.21	472	472
NCAPD2	0.011	0	-9999	-10000	0	0
Aurora B/PP1-gamma	-0.18	0.077	-9999	-0.21	472	472
RHOA	0.011	0	-9999	-10000	0	0
NCAPH	-0.25	0.14	-9999	-0.33	416	416
NPM1	-0.041	0.018	-9999	-10000	0	0
RASA1	0.007	0.04	-9999	-0.41	5	5
KLHL9	0.01	0.018	-9999	-0.41	1	1
mitotic prometaphase	-0.009	0.004	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.18	0.077	-9999	-0.21	472	472
PPP1CC	0.011	0	-9999	-10000	0	0
Centraspindlin	-0.12	0.072	-9999	-0.25	44	44
RhoA/GDP	0.008	0	-9999	-10000	0	0
NSUN2	-0.041	0.018	-9999	-10000	0	0
MYLK	-0.24	0.15	-9999	-0.37	308	308
KIF23	-0.006	0.069	-9999	-0.33	23	23
VIM	-0.18	0.084	-9999	-0.21	472	472
RACGAP1	0.007	0.021	-9999	-0.34	2	2
mitosis	0	0	-9999	-10000	0	0
NCL	-0.041	0.018	-9999	-10000	0	0
Chromosomal passenger complex	-0.14	0.067	-9999	-0.19	291	291
Chromosomal passenger complex/EVI5	-0.26	0.19	-9999	-0.36	417	417
TACC1	-0.066	0.16	-9999	-0.41	98	98
PPP2R5D	0.011	0	-9999	-10000	0	0
CUL3	0.011	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.36	0.4	-9999	-0.83	172	172
HDAC7	0.012	0.001	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.3	0.36	-9999	-0.75	145	145
SMAD4	0.011	0.018	-9999	-0.41	1	1
ID2	-0.36	0.41	-9999	-0.83	172	172
AP1	-0.076	0.14	-9999	-0.29	166	166
ABCG2	-0.46	0.47	-9999	-0.9	243	243
HIF1A	-0.047	0.062	-9999	-10000	0	0
TFF3	-0.42	0.44	-9999	-0.87	205	205
GATA2	-0.028	0.12	-9999	-0.41	51	51
AKT1	-0.061	0.084	-9999	-0.22	18	18
response to hypoxia	-0.078	0.086	-9999	-0.19	111	111
MCL1	-0.36	0.4	-9999	-0.83	171	171
NDRG1	-0.36	0.4	-9999	-0.83	172	172
SERPINE1	-0.36	0.41	-9999	-0.83	172	172
FECH	-0.36	0.4	-9999	-0.83	171	171
FURIN	-0.36	0.4	-9999	-0.83	172	172
NCOA2	-0.003	0.078	-9999	-0.41	19	19
EP300	-0.073	0.13	-9999	-0.34	74	74
HMOX1	-0.36	0.4	-9999	-0.83	174	174
BHLHE40	-0.36	0.4	-9999	-0.82	174	174
BHLHE41	-0.38	0.43	-9999	-0.87	179	179
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.041	0.083	-9999	-0.3	5	5
ENG	-0.025	0.084	-9999	-0.27	5	5
JUN	0.006	0.048	-9999	-0.41	7	7
RORA	-0.37	0.42	-9999	-0.84	178	178
ABCB1	-0.34	0.49	-9999	-1.2	137	137
TFRC	-0.36	0.41	-9999	-0.83	174	174
CXCR4	-0.36	0.4	-9999	-0.82	174	174
TF	-0.37	0.41	-9999	-0.84	176	176
CITED2	-0.37	0.41	-9999	-0.84	172	172
HIF1A/ARNT	-0.39	0.47	-9999	-0.9	188	188
LDHA	-0.053	0.048	-9999	-10000	0	0
ETS1	-0.36	0.4	-9999	-0.83	171	171
PGK1	-0.36	0.4	-9999	-0.82	174	174
NOS2	-0.37	0.41	-9999	-0.83	176	176
ITGB2	-0.36	0.4	-9999	-0.83	174	174
ALDOA	-0.36	0.4	-9999	-0.83	172	172
Cbp/p300/CITED2	-0.39	0.45	-9999	-0.95	156	156
FOS	-0.12	0.19	-9999	-0.41	165	165
HK2	-0.37	0.41	-9999	-0.83	177	177
SP1	0.01	0.023	-9999	-10000	0	0
GCK	-0.23	0.46	-9999	-1.3	75	75
HK1	-0.36	0.4	-9999	-0.82	174	174
NPM1	-0.36	0.4	-9999	-0.82	174	174
EGLN1	-0.36	0.4	-9999	-0.82	174	174
CREB1	0.017	0	-9999	-10000	0	0
PGM1	-0.36	0.4	-9999	-0.83	172	172
SMAD3	0.009	0.036	-9999	-0.41	4	4
EDN1	-0.14	0.24	-9999	-0.66	56	56
IGFBP1	-0.39	0.43	-9999	-0.86	183	183
VEGFA	-0.25	0.32	-9999	-0.69	109	109
HIF1A/JAB1	-0.023	0.036	-9999	-10000	0	0
CP	-0.4	0.43	-9999	-0.87	189	189
CXCL12	-0.49	0.46	-9999	-0.92	235	235
COPS5	0.011	0.003	-9999	-10000	0	0
SMAD3/SMAD4	0.016	0.028	-9999	-0.28	5	5
BNIP3	-0.36	0.4	-9999	-0.83	172	172
EGLN3	-0.36	0.41	-9999	-0.83	172	172
CA9	-0.43	0.44	-9999	-0.86	221	221
TERT	-0.41	0.43	-9999	-0.87	197	197
ENO1	-0.36	0.4	-9999	-0.83	172	172
PFKL	-0.36	0.4	-9999	-0.83	172	172
NCOA1	0.01	0.018	-9999	-0.41	1	1
ADM	-0.37	0.41	-9999	-0.83	183	183
ARNT	-0.048	0.062	-9999	-10000	0	0
HNF4A	-0.049	0.12	-9999	-0.34	78	78
ADFP	-0.37	0.4	-9999	-0.81	188	188
SLC2A1	-0.25	0.32	-9999	-0.69	113	113
LEP	-0.36	0.4	-9999	-0.83	174	174
HIF1A/ARNT/Cbp/p300	-0.32	0.37	-9999	-0.77	155	155
EPO	-0.22	0.29	-9999	-0.78	49	49
CREBBP	-0.074	0.13	-9999	-0.34	75	75
HIF1A/ARNT/Cbp/p300/HDAC7	-0.29	0.36	-9999	-0.75	143	143
PFKFB3	-0.36	0.4	-9999	-0.82	174	174
NT5E	-0.39	0.43	-9999	-0.88	183	183

×

Signaling events regulated by Ret tyrosine kinase

Figure S4. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S4. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.032	0.034	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.13	0.13	-9999	-0.33	101	101
JUN	-0.077	0.13	-9999	-0.39	37	37
HRAS	0.011	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.1	0.13	-9999	-0.23	259	259
RAP1A	0.011	0	-9999	-10000	0	0
FRS2	0.011	0	-9999	-10000	0	0
RAP1A/GDP	0.008	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.1	0.13	-9999	-0.23	258	258
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.011	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.011	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.089	0.11	-9999	-0.21	253	253
RHOA	0.011	0	-9999	-10000	0	0
RAP1A/GTP	-0.098	0.11	-9999	-0.2	258	258
GRB7	-0.01	0.083	-9999	-0.34	33	33
RET51/GFRalpha1/GDNF	-0.1	0.13	-9999	-0.23	258	258
MAPKKK cascade	-0.098	0.11	-9999	-0.37	33	33
BCAR1	0.011	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.11	0.14	-9999	-0.24	268	268
lamellipodium assembly	-0.12	0.13	-9999	-0.24	261	261
RET51/GFRalpha1/GDNF/SHC	-0.1	0.13	-9999	-0.23	258	258
PIK3CA	0.01	0.018	-9999	-0.41	1	1
RET9/GFRalpha1/GDNF/SHC	-0.089	0.11	-9999	-0.21	253	253
RET9/GFRalpha1/GDNF/Shank3	-0.089	0.11	-9999	-0.21	253	253
MAPK3	-0.075	0.11	-9999	-0.34	31	31
DOK1	0.011	0	-9999	-10000	0	0
DOK6	-0.072	0.17	-9999	-0.41	106	106
PXN	0.011	0	-9999	-10000	0	0
neurite development	-0.082	0.12	-9999	-0.27	95	95
DOK5	-0.03	0.12	-9999	-0.41	52	52
GFRA1	-0.19	0.21	-9999	-0.41	253	253
MAPK8	-0.084	0.13	-9999	-0.37	38	38
HRAS/GTP	-0.11	0.12	-9999	-0.23	258	258
tube development	-0.078	0.11	-9999	-0.19	252	252
MAPK1	-0.075	0.11	-9999	-0.34	31	31
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.081	0.11	-9999	-0.2	251	251
Rac1/GDP	0.008	0	-9999	-10000	0	0
SRC	0.011	0	-9999	-10000	0	0
PDLIM7	0.011	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.13	0.16	-9999	-0.25	292	292
SHC1	0.011	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.1	0.13	-9999	-0.23	258	258
RET51/GFRalpha1/GDNF/Dok5	-0.12	0.16	-9999	-0.26	270	270
PRKCA	-0.017	0.1	-9999	-0.41	36	36
HRAS/GDP	0.008	0	-9999	-10000	0	0
CREB1	-0.1	0.14	-9999	-0.25	251	251
PIK3R1	0.007	0.04	-9999	-0.41	5	5
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.083	0.12	-9999	-0.2	251	251
RET51/GFRalpha1/GDNF/Grb7	-0.11	0.14	-9999	-0.24	261	261
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.025	0.11	-9999	-0.37	50	50
DOK4	0.011	0	-9999	-10000	0	0
JNK cascade	-0.076	0.13	-9999	-0.38	37	37
RET9/GFRalpha1/GDNF/FRS2	-0.089	0.11	-9999	-0.21	252	252
SHANK3	0.011	0	-9999	-10000	0	0
RASA1	0.007	0.04	-9999	-0.41	5	5
NCK1	0.009	0.026	-9999	-0.41	2	2
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.082	0.11	-9999	-0.2	251	251
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.09	0.13	-9999	-0.21	258	258
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.094	0.14	-9999	-0.22	259	259
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.094	0.14	-9999	-0.22	257	257
PI3K	-0.16	0.21	-9999	-0.36	261	261
SOS1	0.011	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.077	0.11	-9999	-0.19	252	252
GRB10	0.01	0.018	-9999	-0.41	1	1
activation of MAPKK activity	-0.082	0.11	-9999	-0.2	252	252
RET51/GFRalpha1/GDNF/FRS2	-0.1	0.13	-9999	-0.23	258	258
GAB1	0.008	0.036	-9999	-0.41	4	4
IRS1	-0.03	0.12	-9999	-0.41	53	53
IRS2	-0.043	0.14	-9999	-0.41	69	69
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.097	0.14	-9999	-0.23	258	258
RET51/GFRalpha1/GDNF/PKC alpha	-0.12	0.15	-9999	-0.24	269	269
GRB2	0.011	0	-9999	-10000	0	0
PRKACA	0.011	0	-9999	-10000	0	0
GDNF	0.003	0.026	-9999	-0.33	3	3
RAC1	0.011	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.12	0.16	-9999	-0.26	272	272
Rac1/GTP	-0.15	0.15	-9999	-0.28	261	261
RET9/GFRalpha1/GDNF	-0.11	0.13	-9999	-0.24	253	253
GFRalpha1/GDNF	-0.13	0.15	-9999	-0.29	253	253

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.088	0.2	-10000	0	-0.39	115	115
PTK2B	0.011	0.001	-10000	0	-10000	0	0
mol:Ca2+	-0.12	0.31	-10000	0	-0.79	81	81
EDN1	-0.001	0.089	-10000	0	-0.39	11	11
EDN3	-0.1	0.17	-10000	0	-0.36	159	159
EDN2	-0.042	0.12	-10000	0	-0.33	84	84
HRAS/GDP	-0.12	0.21	-10000	0	-0.42	136	136
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.084	0.18	-10000	0	-0.36	125	125
ADCY4	-0.11	0.19	-10000	0	-0.38	140	140
ADCY5	-0.14	0.2	-10000	0	-0.4	161	161
ADCY6	-0.1	0.18	-10000	0	-0.37	136	136
ADCY7	-0.1	0.18	-10000	0	-0.37	133	133
ADCY1	-0.11	0.2	-10000	0	-0.38	147	147
ADCY2	-0.21	0.23	-10000	0	-0.46	205	205
ADCY3	-0.1	0.19	-10000	0	-0.37	133	133
ADCY8	-0.11	0.18	-10000	0	-0.37	136	136
ADCY9	-0.13	0.22	-10000	0	-0.42	154	154
arachidonic acid secretion	-0.17	0.28	-10000	0	-0.46	217	217
ETB receptor/Endothelin-1/Gq/GTP	-0.067	0.15	-10000	0	-0.33	103	103
GNAO1	-0.1	0.18	-10000	0	-0.41	142	142
HRAS	0.009	0.004	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	-0.057	0.21	0.17	4	-0.36	116	120
ETA receptor/Endothelin-1/Gs/GTP	-0.087	0.22	0.16	100	-0.39	136	236
mol:GTP	-0.002	0.005	-10000	0	-10000	0	0
COL3A1	-0.096	0.22	-10000	0	-0.42	117	117
EDNRB	-0.084	0.18	-10000	0	-0.41	123	123
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.13	0.25	-10000	0	-0.52	127	127
CYSLTR1	-0.093	0.21	-10000	0	-0.47	83	83
SLC9A1	-0.057	0.11	-10000	0	-0.24	91	91
mol:GDP	-0.13	0.22	-10000	0	-0.45	137	137
SLC9A3	-0.14	0.3	-10000	0	-0.62	132	132
RAF1	-0.16	0.24	-10000	0	-0.42	204	204
JUN	-0.1	0.26	-10000	0	-0.67	75	75
JAK2	-0.092	0.2	-10000	0	-0.38	127	127
mol:IP3	-0.09	0.18	-10000	0	-0.4	95	95
ETA receptor/Endothelin-1	-0.084	0.26	-10000	0	-0.42	148	148
PLCB1	0.006	0.032	-10000	0	-0.41	3	3
PLCB2	0.008	0.005	-10000	0	-10000	0	0
ETA receptor/Endothelin-3	-0.16	0.19	-10000	0	-0.32	281	281
FOS	-0.29	0.43	-10000	0	-0.84	186	186
Gai/GDP	-0.19	0.34	-10000	0	-0.73	143	143
CRK	0.011	0.001	-10000	0	-10000	0	0
mol:Ca ++	-0.14	0.25	-10000	0	-0.47	153	153
BCAR1	0.011	0	-10000	0	-10000	0	0
PRKCB1	-0.091	0.17	-10000	0	-0.38	101	101
GNAQ	0.007	0.026	-10000	0	-0.41	2	2
GNAZ	-0.001	0.069	-10000	0	-0.41	15	15
GNAL	-0.051	0.15	-10000	0	-0.41	79	79
Gs family/GDP	-0.16	0.2	-10000	0	-0.42	166	166
ETA receptor/Endothelin-1/Gq/GTP	-0.097	0.21	-10000	0	-0.41	127	127
MAPK14	-0.051	0.13	-10000	0	-0.33	64	64
TRPC6	-0.14	0.34	-10000	0	-0.85	81	81
GNAI2	0.011	0	-10000	0	-10000	0	0
GNAI3	0.011	0	-10000	0	-10000	0	0
GNAI1	0.005	0.051	-10000	0	-0.41	8	8
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.06	0.14	-10000	0	-0.33	80	80
ETB receptor/Endothelin-2	-0.085	0.15	-10000	0	-0.28	182	182
ETB receptor/Endothelin-3	-0.12	0.16	-10000	0	-0.28	251	251
ETB receptor/Endothelin-1	-0.056	0.15	-10000	0	-0.3	130	130
MAPK3	-0.26	0.38	-10000	0	-0.73	194	194
MAPK1	-0.26	0.38	-10000	0	-0.73	194	194
Rac1/GDP	-0.12	0.21	-10000	0	-0.42	135	135
cAMP biosynthetic process	-0.19	0.24	-10000	0	-0.43	217	217
MAPK8	-0.13	0.3	-10000	0	-0.73	85	85
SRC	0.011	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.087	0.16	-10000	0	-0.33	125	125
p130Cas/CRK/Src/PYK2	-0.11	0.23	-10000	0	-0.53	99	99
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.12	0.21	-10000	0	-0.42	135	135
COL1A2	-0.13	0.25	-10000	0	-0.52	121	121
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.12	0.18	-10000	0	-0.32	220	220
mol:DAG	-0.09	0.18	-10000	0	-0.4	95	95
MAP2K2	-0.2	0.3	-10000	0	-0.55	199	199
MAP2K1	-0.2	0.3	-10000	0	-0.55	199	199
EDNRA	-0.13	0.24	-10000	0	-0.47	163	163
positive regulation of muscle contraction	-0.07	0.17	-10000	0	-0.33	115	115
Gq family/GDP	-0.14	0.19	-10000	0	-0.44	110	110
HRAS/GTP	-0.13	0.21	-10000	0	-0.41	139	139
PRKCH	-0.086	0.18	-10000	0	-0.41	85	85
RAC1	0.011	0	-10000	0	-10000	0	0
PRKCA	-0.098	0.19	-10000	0	-0.44	91	91
PRKCB	-0.097	0.19	-10000	0	-0.42	102	102
PRKCE	-0.084	0.17	-10000	0	-0.41	80	80
PRKCD	-0.086	0.17	-10000	0	-0.42	78	78
PRKCG	-0.11	0.18	-10000	0	-0.39	116	116
regulation of vascular smooth muscle contraction	-0.34	0.5	-10000	0	-0.99	186	186
PRKCQ	-0.1	0.18	-10000	0	-0.4	110	110
PLA2G4A	-0.19	0.31	-10000	0	-0.51	217	217
GNA14	-0.034	0.13	-10000	0	-0.41	55	55
GNA15	0.004	0.039	-10000	0	-0.34	7	7
GNA12	0.011	0	-10000	0	-10000	0	0
GNA11	-0.001	0.063	-10000	0	-0.41	12	12
Rac1/GTP	-0.057	0.21	0.17	107	-0.36	116	223
MMP1	-0.052	0.15	0.27	8	-10000	0	8

×

Angiopoietin receptor Tie2-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
AKT1	-0.19	0.44	-10000	0	-0.84	166	166
NCK1/PAK1/Dok-R	-0.12	0.18	-10000	0	-0.4	166	166
NCK1/Dok-R	-0.26	0.51	-10000	0	-0.99	166	166
PIK3CA	0.011	0.018	-10000	0	-0.41	1	1
mol:beta2-estradiol	0.043	0.095	0.23	108	-10000	0	108
RELA	0.011	0	-10000	0	-10000	0	0
SHC1	0.011	0.002	-10000	0	-10000	0	0
Rac/GDP	0.008	0	-10000	0	-10000	0	0
F2	0.026	0.14	0.25	108	-0.34	39	147
TNIP2	0.011	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.28	0.44	-10000	0	-0.92	166	166
FN1	0.007	0.04	-10000	0	-0.41	5	5
PLD2	-0.28	0.53	-10000	0	-1	166	166
PTPN11	0.011	0	-10000	0	-10000	0	0
GRB14	-0.11	0.16	-10000	0	-0.33	195	195
ELK1	-0.24	0.47	-10000	0	-0.93	166	166
GRB7	-0.01	0.083	-10000	0	-0.34	33	33
PAK1	0.011	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.3	0.47	-10000	0	-0.97	166	166
CDKN1A	-0.11	0.3	-10000	0	-0.61	109	109
ITGA5	0.011	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.26	0.51	-10000	0	-1	166	166
CRK	0.011	0	-10000	0	-10000	0	0
mol:NO	-0.13	0.33	-10000	0	-0.62	166	166
PLG	-0.3	0.53	-10000	0	-1	166	166
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.22	0.4	-10000	0	-0.8	166	166
GRB2	0.011	0	-10000	0	-10000	0	0
PIK3R1	0.007	0.041	-10000	0	-0.41	5	5
ANGPT2	-0.06	0.2	-10000	0	-0.55	37	37
BMX	-0.3	0.54	-10000	0	-1.1	166	166
ANGPT1	-0.22	0.48	-10000	0	-1.2	108	108
tube development	-0.13	0.33	-10000	0	-0.61	164	164
ANGPT4	0	0.045	-10000	0	-0.39	7	7
response to hypoxia	-0.017	0.032	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.32	0.56	-10000	0	-1.1	166	166
alpha5/beta1 Integrin	0.016	0	-10000	0	-10000	0	0
FGF2	-0.22	0.21	-10000	0	-0.41	291	291
STAT5A (dimer)	-0.15	0.38	-10000	0	-0.75	128	128
mol:L-citrulline	-0.13	0.33	-10000	0	-0.62	166	166
AGTR1	-0.085	0.17	-10000	0	-0.41	121	121
MAPK14	-0.28	0.54	-10000	0	-1.1	166	166
Tie2/SHP2	-0.21	0.4	-10000	0	-1.1	91	91
TEK	-0.2	0.46	-10000	0	-1.2	91	91
RPS6KB1	-0.19	0.42	-10000	0	-0.8	166	166
Angiotensin II/AT1	-0.057	0.12	-10000	0	-0.28	121	121
Tie2/Ang1/GRB2	-0.29	0.55	-10000	0	-1.1	166	166
MAPK3	-0.25	0.48	-10000	0	-0.95	166	166
MAPK1	-0.25	0.48	-10000	0	-0.95	166	166
Tie2/Ang1/GRB7	-0.29	0.55	-10000	0	-1.1	166	166
NFKB1	0.01	0.018	-10000	0	-0.41	1	1
MAPK8	-0.28	0.53	-10000	0	-1	166	166
PI3K	-0.24	0.5	-10000	0	-0.96	166	166
FES	-0.27	0.54	-10000	0	-1	166	166
Crk/Dok-R	-0.26	0.51	-10000	0	-0.99	166	166
Tie2/Ang1/ABIN2	-0.29	0.55	-10000	0	-1.1	166	166
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.17	0.39	-10000	0	-0.74	166	166
STAT5A	0.01	0.018	-10000	0	-0.41	1	1
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.19	0.42	-10000	0	-0.8	166	166
Tie2/Ang2	-0.19	0.45	-10000	0	-0.85	150	150
Tie2/Ang1	-0.31	0.58	-10000	0	-1.1	166	166
FOXO1	-0.16	0.4	-10000	0	-0.75	166	166
ELF1	-0.006	0.054	-10000	0	-0.44	4	4
ELF2	-0.28	0.53	-10000	0	-1	166	166
mol:Choline	-0.26	0.5	-10000	0	-0.98	166	166
cell migration	-0.07	0.1	-10000	0	-0.22	166	166
FYN	-0.15	0.38	-10000	0	-0.7	162	162
DOK2	0.008	0.031	-10000	0	-0.35	4	4
negative regulation of cell cycle	-0.094	0.28	-10000	0	-0.54	124	124
ETS1	-0.031	0.095	-10000	0	-0.22	98	98
PXN	-0.14	0.35	-10000	0	-0.66	166	166
ITGB1	0.011	0	-10000	0	-10000	0	0
NOS3	-0.15	0.37	-10000	0	-0.7	166	166
RAC1	0.011	0	-10000	0	-10000	0	0
TNF	-0.074	0.15	-10000	0	-0.28	165	165
MAPKKK cascade	-0.26	0.5	-10000	0	-0.98	166	166
RASA1	0.007	0.04	-10000	0	-0.41	5	5
Tie2/Ang1/Shc	-0.29	0.55	-10000	0	-1.1	166	166
NCK1	0.009	0.026	-10000	0	-0.41	2	2
vasculogenesis	-0.11	0.3	-10000	0	-0.55	166	166
mol:Phosphatidic acid	-0.26	0.5	-10000	0	-0.98	166	166
mol:Angiotensin II	0.001	0.001	-10000	0	-10000	0	0
mol:NADP	-0.13	0.33	-10000	0	-0.62	166	166
Rac1/GTP	-0.23	0.35	-10000	0	-0.75	166	166
MMP2	-0.28	0.54	-10000	0	-1	166	166

×

p75(NTR)-mediated signaling

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
Sortilin/TRAF6	0.016	0	-10000	0	-10000	0	0
Necdin/E2F1	-0.17	0.18	-10000	0	-0.31	300	300
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.085	0.14	-10000	0	-0.38	65	65
NGF (dimer)/p75(NTR)/BEX1	-0.16	0.2	-10000	0	-0.33	278	278
NT-4/5 (dimer)/p75(NTR)	-0.096	0.14	-10000	0	-0.28	202	202
IKBKB	0.011	0	-10000	0	-10000	0	0
AKT1	-0.085	0.14	-10000	0	-0.38	65	65
IKBKG	0.011	0	-10000	0	-10000	0	0
BDNF	-0.042	0.12	-10000	0	-0.33	84	84
MGDIs/NGR/p75(NTR)/LINGO1	-0.065	0.12	-10000	0	-0.23	189	189
FURIN	0.011	0	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.092	0.12	-10000	0	-0.22	254	254
LINGO1	0.006	0.04	-10000	0	-0.34	7	7
Sortilin/TRAF6/NRIF	-0.002	0.016	-10000	0	-10000	0	0
proBDNF (dimer)	-0.042	0.12	-10000	0	-0.33	84	84
NTRK1	0.001	0.058	-10000	0	-0.37	13	13
RTN4R	0.01	0.018	-10000	0	-0.41	1	1
neuron apoptosis	-0.092	0.14	-10000	0	-0.35	70	70
IRAK1	0.011	0	-10000	0	-10000	0	0
SHC1	-0.11	0.17	-10000	0	-0.29	232	232
ARHGDIA	0.011	0	-10000	0	-10000	0	0
RhoA/GTP	0.008	0	-10000	0	-10000	0	0
Gamma Secretase	0.03	0.024	-10000	0	-0.18	7	7
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.15	0.19	-10000	0	-0.29	293	293
MAGEH1	-0.09	0.18	-10000	0	-0.41	129	129
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.2	0.2	-10000	0	-0.32	355	355
Mammalian IAPs/DIABLO	0.024	0.029	-10000	0	-0.2	8	8
proNGF (dimer)	-0.078	0.17	-10000	0	-0.41	114	114
MAGED1	0.009	0.026	-10000	0	-0.41	2	2
APP	0.011	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.007	0.071	-10000	0	-0.33	24	24
ZNF274	0.011	0	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.088	0.14	-10000	0	-0.24	232	232
NGF	-0.078	0.17	-10000	0	-0.41	114	114
cell cycle arrest	-0.079	0.13	0.14	40	-0.36	63	103
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.09	0.15	-10000	0	-0.25	232	232
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.072	0.12	-10000	0	-0.23	182	182
NCSTN	0.011	0	-10000	0	-10000	0	0
mol:GTP	-0.11	0.17	-10000	0	-0.29	236	236
PSENEN	0.011	0	-10000	0	-10000	0	0
mol:ceramide	-0.094	0.15	-10000	0	-0.25	232	232
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.071	0.13	-10000	0	-0.34	63	63
p75(NTR)/beta APP	-0.084	0.14	-10000	0	-0.28	182	182
BEX1	-0.074	0.17	-10000	0	-0.41	109	109
mol:GDP	-0.12	0.16	-10000	0	-0.29	233	233
NGF (dimer)	-0.078	0.14	-10000	0	-0.25	177	177
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.051	0.11	-10000	0	-0.2	182	182
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
RAC1/GTP	-0.095	0.14	-10000	0	-0.24	232	232
MYD88	0.011	0	-10000	0	-10000	0	0
CHUK	0.011	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.12	0.17	-10000	0	-0.29	236	236
RHOB	0.009	0.026	-10000	0	-0.41	2	2
RHOA	0.011	0	-10000	0	-10000	0	0
MAGE-G1/E2F1	-0.028	0.091	-10000	0	-0.22	101	101
NT3 (dimer)	-0.018	0.1	-10000	0	-0.4	37	37
TP53	-0.057	0.1	-10000	0	-0.31	12	12
PRDM4	-0.095	0.15	-10000	0	-0.25	232	232
BDNF (dimer)	-0.089	0.14	-10000	0	-0.29	114	114
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
SORT1	0.011	0	-10000	0	-10000	0	0
activation of caspase activity	-0.1	0.13	-10000	0	-0.38	65	65
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.094	0.15	-10000	0	-0.26	232	232
RHOC	0.011	0	-10000	0	-10000	0	0
XIAP	0.011	0	-10000	0	-10000	0	0
MAPK10	-0.13	0.18	-10000	0	-0.4	128	128
DIABLO	0.011	0	-10000	0	-10000	0	0
SMPD2	-0.095	0.15	-10000	0	-0.25	232	232
APH1B	0.006	0.048	-10000	0	-0.41	7	7
APH1A	0.011	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.11	0.17	-10000	0	-0.29	232	232
PSEN1	0.011	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.016	0	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.1	0.16	-10000	0	-0.3	204	204
MAPK8	-0.094	0.15	-10000	0	-0.36	77	77
MAPK9	-0.092	0.15	-10000	0	-0.36	75	75
APAF1	0.011	0	-10000	0	-10000	0	0
NTF3	-0.018	0.1	-10000	0	-0.4	37	37
NTF4	-0.007	0.071	-10000	0	-0.33	24	24
NDN	-0.19	0.21	-10000	0	-0.41	262	262
RAC1/GDP	0.008	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.094	0.12	-10000	0	-0.35	65	65
p75 CTF/Sortilin/TRAF6/NRIF	0.028	0	-10000	0	-10000	0	0
RhoA-B-C/GTP	-0.11	0.17	-10000	0	-0.29	236	236
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.065	0.11	-10000	0	-0.32	13	13
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.076	0.11	-10000	0	-0.21	181	181
PRKACB	0.006	0.044	-10000	0	-0.41	6	6
proBDNF (dimer)/p75 ECD	-0.02	0.085	-10000	0	-0.22	84	84
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.003	0.055	-10000	0	-0.39	10	10
BIRC2	0.011	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.19	0.2	0.15	17	-0.36	260	277
BAD	-0.11	0.16	-10000	0	-0.35	121	121
RIPK2	0.011	0	-10000	0	-10000	0	0
NGFR	-0.13	0.2	-10000	0	-0.41	182	182
CYCS	-0.084	0.14	-10000	0	-0.37	64	64
ADAM17	0.011	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.094	0.15	-10000	0	-0.26	232	232
BCL2L11	-0.11	0.16	-10000	0	-0.35	121	121
BDNF (dimer)/p75(NTR)	-0.12	0.15	-10000	0	-0.27	254	254
PI3K	-0.096	0.15	-10000	0	-0.26	236	236
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.094	0.15	-10000	0	-0.26	232	232
NDNL2	0.011	0	-10000	0	-10000	0	0
YWHAE	0.011	0	-10000	0	-10000	0	0
PRKCI	0.011	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.14	0.19	-10000	0	-0.35	233	233
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.095	0.15	-10000	0	-0.26	234	234
TRAF6	0.011	0	-10000	0	-10000	0	0
RAC1	0.011	0	-10000	0	-10000	0	0
PRKCZ	0.01	0.023	-10000	0	-0.37	2	2
PLG	-0.033	0.12	-10000	0	-0.4	55	55
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.12	0.16	-10000	0	-0.3	186	186
SQSTM1	0.011	0	-10000	0	-10000	0	0
NGFRAP1	0.006	0.044	-10000	0	-0.41	6	6
CASP3	-0.1	0.16	-10000	0	-0.33	121	121
E2F1	-0.053	0.13	-10000	0	-0.33	101	101
CASP9	0.011	0	-10000	0	-10000	0	0
IKK complex	-0.093	0.13	-10000	0	-0.31	120	120
NGF (dimer)/TRKA	-0.053	0.13	-10000	0	-0.28	125	125
MMP7	-0.057	0.14	-10000	0	-0.36	98	98
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.083	0.14	-10000	0	-0.38	63	63
MMP3	-0.051	0.13	-10000	0	-0.33	96	96
APAF-1/Caspase 9	-0.072	0.093	-10000	0	-0.28	64	64

×

PDGFR-alpha signaling pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.12	0.19	-9999	-0.43	147	147
PDGF/PDGFRA/CRKL	-0.069	0.13	-9999	-0.28	147	147
positive regulation of JUN kinase activity	-0.036	0.098	-9999	-0.21	57	57
CRKL	0.011	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.076	0.13	-9999	-0.29	148	148
AP1	-0.29	0.39	-9999	-0.86	165	165
mol:IP3	-0.08	0.14	-9999	-0.3	147	147
PLCG1	-0.08	0.14	-9999	-0.3	147	147
PDGF/PDGFRA/alphaV Integrin	-0.069	0.13	-9999	-0.28	147	147
RAPGEF1	0.011	0	-9999	-10000	0	0
CRK	0.011	0	-9999	-10000	0	0
mol:Ca2+	-0.08	0.14	-9999	-0.3	147	147
CAV3	0.002	0.015	-9999	-0.33	1	1
CAV1	-0.062	0.16	-9999	-0.41	94	94
SHC/Grb2/SOS1	-0.036	0.099	-9999	-0.21	57	57
PDGF/PDGFRA/Shf	-0.072	0.14	-9999	-0.29	149	149
FOS	-0.27	0.4	-9999	-0.85	165	165
JUN	-0.026	0.045	-9999	-0.34	7	7
oligodendrocyte development	-0.069	0.13	-9999	-0.28	147	147
GRB2	0.011	0	-9999	-10000	0	0
PIK3R1	0.007	0.04	-9999	-0.41	5	5
mol:DAG	-0.08	0.14	-9999	-0.3	147	147
PDGF/PDGFRA	-0.12	0.19	-9999	-0.42	147	147
actin cytoskeleton reorganization	-0.069	0.13	-9999	-0.28	147	147
SRF	0.025	0.011	-9999	-10000	0	0
SHC1	0.011	0	-9999	-10000	0	0
PI3K	-0.051	0.11	-9999	-0.23	150	150
PDGF/PDGFRA/Crk/C3G	-0.049	0.11	-9999	-0.23	147	147
JAK1	-0.069	0.13	-9999	-0.28	147	147
ELK1/SRF	-0.041	0.11	-9999	-0.22	147	147
SHB	0.011	0	-9999	-10000	0	0
SHF	0.006	0.048	-9999	-0.41	7	7
CSNK2A1	0.021	0.024	-9999	-10000	0	0
GO:0007205	-0.09	0.15	-9999	-0.34	147	147
SOS1	0.011	0	-9999	-10000	0	0
Ras protein signal transduction	-0.036	0.098	-9999	-0.21	57	57
PDGF/PDGFRA/SHB	-0.069	0.13	-9999	-0.28	147	147
PDGF/PDGFRA/Caveolin-1	-0.12	0.19	-9999	-0.35	189	189
ITGAV	0.011	0	-9999	-10000	0	0
ELK1	-0.081	0.14	-9999	-0.29	147	147
PIK3CA	0.01	0.018	-9999	-0.41	1	1
PDGF/PDGFRA/Crk	-0.069	0.13	-9999	-0.28	147	147
JAK-STAT cascade	-0.069	0.13	-9999	-0.28	147	147
cell proliferation	-0.072	0.14	-9999	-0.29	149	149

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.055	0.18	-10000	0	-0.59	37	37
IHH	-0.13	0.2	-10000	0	-0.39	187	187
SHH Np/Cholesterol/GAS1	-0.15	0.13	-10000	0	-0.23	345	345
LRPAP1	0.011	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.14	0.13	0.23	345	-10000	0	345
SMO/beta Arrestin2	-0.052	0.16	-10000	0	-0.3	135	135
SMO	-0.06	0.16	-10000	0	-0.32	136	136
AKT1	-0.018	0.096	-10000	0	-0.47	6	6
ARRB2	0.011	0	-10000	0	-10000	0	0
BOC	-0.003	0.076	-10000	0	-0.41	18	18
ADRBK1	0.011	0	-10000	0	-10000	0	0
heart looping	-0.06	0.16	-10000	0	-0.31	136	136
STIL	-0.048	0.12	-10000	0	-0.34	33	33
DHH N/PTCH2	-0.023	0.1	-10000	0	-0.3	68	68
DHH N/PTCH1	-0.059	0.14	-10000	0	-0.35	52	52
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
DHH	-0.023	0.11	-10000	0	-0.41	42	42
PTHLH	-0.07	0.21	-10000	0	-0.65	37	37
determination of left/right symmetry	-0.06	0.16	-10000	0	-0.31	136	136
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
skeletal system development	-0.069	0.21	-10000	0	-0.64	37	37
IHH N/Hhip	-0.079	0.13	-10000	0	-0.26	157	157
DHH N/Hhip	-0.023	0.098	-10000	0	-0.26	75	75
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.06	0.16	-10000	0	-0.31	136	136
pancreas development	-0.013	0.088	-10000	0	-0.34	35	35
HHAT	0.008	0.036	-10000	0	-0.41	4	4
PI3K	0.013	0.031	-10000	0	-0.28	6	6
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.26	0.2	-10000	0	-0.41	343	343
somite specification	-0.06	0.16	-10000	0	-0.31	136	136
SHH Np/Cholesterol/PTCH1	-0.052	0.12	-10000	0	-0.36	27	27
SHH Np/Cholesterol/PTCH2	-0.017	0.08	-10000	0	-0.18	98	98
SHH Np/Cholesterol/Megalin	-0.067	0.1	-10000	0	-0.24	64	64
SHH	-0.015	0.082	-10000	0	-0.22	72	72
catabolic process	-0.054	0.14	-10000	0	-0.26	151	151
SMO/Vitamin D3	-0.049	0.14	-10000	0	-0.4	27	27
SHH Np/Cholesterol/Hhip	-0.017	0.075	-10000	0	-0.17	103	103
LRP2	-0.11	0.16	-10000	0	-0.33	192	192
receptor-mediated endocytosis	-0.076	0.14	-10000	0	-0.32	79	79
SHH Np/Cholesterol/BOC	-0.012	0.073	-10000	0	-0.17	87	87
SHH Np/Cholesterol/CDO	-0.029	0.097	-10000	0	-0.2	117	117
mesenchymal cell differentiation	0.017	0.074	0.17	103	-10000	0	103
mol:Vitamin D3	-0.041	0.12	-10000	0	-0.35	28	28
IHH N/PTCH2	-0.079	0.14	-10000	0	-0.28	147	147
CDON	-0.035	0.13	-10000	0	-0.41	59	59
IHH N/PTCH1	-0.035	0.15	-10000	0	-0.26	151	151
Megalin/LRPAP1	-0.068	0.11	-10000	0	-0.22	192	192
PTCH2	-0.012	0.096	-10000	0	-0.41	30	30
SHH Np/Cholesterol	-0.012	0.061	-10000	0	-0.16	72	72
PTCH1	-0.054	0.14	-10000	0	-0.26	151	151
HHIP	-0.013	0.088	-10000	0	-0.34	35	35

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.001	0.07	-9999	-0.28	32	32
alphaV beta3 Integrin	-0.16	0.16	-9999	-0.28	316	316
PTK2	-0.13	0.19	-9999	-0.41	131	131
IGF1R	-0.005	0.081	-9999	-0.41	21	21
PI4KB	0.011	0	-9999	-10000	0	0
MFGE8	0.009	0.026	-9999	-0.41	2	2
SRC	0.011	0	-9999	-10000	0	0
CDKN1B	-0.14	0.21	-9999	-0.58	86	86
VEGFA	0.011	0	-9999	-10000	0	0
ILK	-0.12	0.18	-9999	-0.55	69	69
ROCK1	0.011	0	-9999	-10000	0	0
AKT1	-0.1	0.17	-9999	-0.52	69	69
PTK2B	-0.02	0.1	-9999	-0.21	115	115
alphaV/beta3 Integrin/JAM-A	-0.15	0.16	-9999	-0.4	116	116
CBL	0.011	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.028	0.098	-9999	-0.23	101	101
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.044	0.14	-9999	-0.26	135	135
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.038	0.12	-9999	-0.35	30	30
alphaV/beta3 Integrin/Syndecan-1	-0.078	0.12	-9999	-0.21	237	237
PI4KA	0.011	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.18	0.18	-9999	-0.42	154	154
PI4 Kinase	0.016	0	-9999	-10000	0	0
PIK3CA	0.01	0.018	-9999	-0.41	1	1
alphaV/beta3 Integrin/Osteopontin	-0.079	0.12	-9999	-0.21	237	237
RPS6KB1	-0.15	0.18	-9999	-0.39	154	154
TLN1	0.011	0	-9999	-10000	0	0
MAPK3	-0.29	0.28	-9999	-0.5	316	316
GPR124	-0.089	0.18	-9999	-0.41	128	128
MAPK1	-0.29	0.28	-9999	-0.5	316	316
PXN	0.011	0	-9999	-10000	0	0
PIK3R1	0.007	0.04	-9999	-0.41	5	5
alphaV/beta3 Integrin/Tumstatin	-0.052	0.12	-9999	-0.24	149	149
cell adhesion	-0.033	0.094	-9999	-0.23	98	98
ANGPTL3	0.004	0.021	-9999	-0.33	2	2
VEGFR2 homodimer/VEGFA homodimer/Src	0.008	0.059	-9999	-0.23	32	32
IGF-1R heterotetramer	-0.005	0.081	-9999	-0.41	21	21
Rac1/GDP	0.008	0	-9999	-10000	0	0
TGFBR2	0.002	0.062	-9999	-0.41	12	12
ITGB3	-0.067	0.16	-9999	-0.41	100	100
IGF1	-0.068	0.16	-9999	-0.41	101	101
RAC1	0.011	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.081	0.15	-9999	-0.27	187	187
apoptosis	0.011	0	-9999	-10000	0	0
CD47	0.011	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.024	0.097	-9999	-0.23	100	100
VCL	0.011	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.07	0.15	-9999	-0.28	165	165
CSF1	0.003	0.057	-9999	-0.41	10	10
PIK3C2A	-0.12	0.18	-9999	-0.55	69	69
PI4 Kinase/Pyk2	-0.14	0.14	-9999	-0.35	128	128
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.026	0.11	-9999	-0.23	115	115
FAK1/Vinculin	-0.098	0.15	-9999	-0.34	121	121
alphaV beta3/Integrin/ppsTEM5	-0.081	0.15	-9999	-0.28	187	187
RHOA	0.011	0	-9999	-10000	0	0
VTN	-0.046	0.14	-9999	-0.41	72	72
BCAR1	0.011	0	-9999	-10000	0	0
FGF2	-0.22	0.21	-9999	-0.41	291	291
F11R	-0.14	0.15	-9999	-0.28	292	292
alphaV/beta3 Integrin/Lactadherin	-0.025	0.099	-9999	-0.23	100	100
alphaV/beta3 Integrin/TGFBR2	-0.029	0.11	-9999	-0.25	103	103
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.024	0.031	-9999	-0.2	10	10
HSP90AA1	0.011	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.02	0.087	-9999	-0.2	100	100
mol:GDP	0	0	-9999	-10000	0	0
FN1	0.007	0.04	-9999	-0.41	5	5
alphaV/beta3 Integrin/Pyk2	-0.019	0.1	-9999	-0.21	115	115
SDC1	-0.085	0.15	-9999	-0.33	152	152
VAV3	-0.012	0.074	-9999	-0.33	1	1
PTPN11	0.011	0	-9999	-10000	0	0
IRS1	-0.03	0.12	-9999	-0.41	53	53
FAK1/Paxillin	-0.098	0.15	-9999	-0.34	121	121
cell migration	-0.084	0.14	-9999	-0.31	118	118
ITGAV	0.011	0	-9999	-10000	0	0
PI3K	-0.14	0.14	-9999	-0.36	119	119
SPP1	-0.086	0.15	-9999	-0.33	153	153
KDR	-0.014	0.099	-9999	-0.41	32	32
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.011	0	-9999	-10000	0	0
COL4A3	-0.038	0.13	-9999	-0.39	65	65
angiogenesis	-0.29	0.28	-9999	-0.5	317	317
Rac1/GTP	-0.005	0.068	-9999	-0.3	1	1
EDIL3	-0.071	0.17	-9999	-0.41	104	104
cell proliferation	-0.029	0.11	-9999	-0.24	103	103

×

Cellular roles of Anthrax toxin

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
ANTXR1	-0.004	0.078	-10000	0	-0.41	19	19
ANTXR2	-0.13	0.2	-10000	0	-0.41	177	177
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.019	0.028	-10000	0	-0.057	181	181
monocyte activation	-0.028	0.11	-10000	0	-0.41	41	41
MAP2K2	-0.007	0.011	-10000	0	-10000	0	0
MAP2K1	-0.016	0.023	-10000	0	-10000	0	0
MAP2K7	-0.016	0.023	-10000	0	-0.078	15	15
MAP2K6	-0.036	0.055	-10000	0	-0.17	69	69
CYAA	-0.064	0.11	-10000	0	-0.21	181	181
MAP2K4	-0.016	0.025	-10000	0	-0.25	1	1
IL1B	-0.011	0.042	-10000	0	-0.14	30	30
Channel	-0.067	0.12	-10000	0	-0.23	181	181
NLRP1	-0.026	0.053	-10000	0	-0.24	26	26
CALM1	0.011	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.021	0.03	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.019	0.028	0.057	181	-10000	0	181
MAPK3	-0.016	0.023	-10000	0	-10000	0	0
MAPK1	-0.016	0.023	-10000	0	-10000	0	0
PGR	-0.077	0.1	-10000	0	-0.23	162	162
PA/Cellular Receptors	-0.075	0.13	-10000	0	-0.25	181	181
apoptosis	-0.019	0.028	-10000	0	-0.057	181	181
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.064	0.11	-10000	0	-0.22	181	181
macrophage activation	-0.003	0.026	-10000	0	-10000	0	0
TNF	-0.032	0.11	-10000	0	-0.33	67	67
VCAM1	-0.028	0.11	-10000	0	-0.41	41	41
platelet activation	-0.021	0.03	-10000	0	-10000	0	0
MAPKKK cascade	0.013	0.031	0.085	32	-10000	0	32
IL18	-0.012	0.043	-10000	0	-0.14	35	35
negative regulation of macrophage activation	-0.019	0.028	-10000	0	-0.057	181	181
LEF	-0.019	0.028	-10000	0	-0.058	181	181
CASP1	-0.021	0.036	-10000	0	-0.12	41	41
mol:cAMP	-0.021	0.03	-10000	0	-10000	0	0
necrosis	-0.019	0.028	-10000	0	-0.057	181	181
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.063	0.11	-10000	0	-0.21	181	181
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.006	0.083	-9999	-0.41	22	22
mol:S1P	-0.009	0.014	-9999	-10000	0	0
S1P1/S1P/Gi	-0.072	0.12	-9999	-0.24	154	154
GNAO1	-0.11	0.19	-9999	-0.42	142	142
S1P/S1P3/G12/G13	0.003	0.046	-9999	-0.22	19	19
AKT1	-0.062	0.16	-9999	-0.66	25	25
AKT3	-0.41	0.55	-9999	-1.1	202	202
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.006	0.083	-9999	-0.41	22	22
GNAI2	0.002	0.014	-9999	-10000	0	0
GNAI3	0.004	0.011	-9999	-10000	0	0
GNAI1	-0.002	0.053	-9999	-0.42	8	8
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	-0.013	0.08	-9999	-0.42	19	19
S1PR2	0.011	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	-0.13	0.2	-9999	-0.31	260	260
MAPK3	-0.12	0.19	-9999	-0.32	208	208
MAPK1	-0.12	0.19	-9999	-0.32	208	208
JAK2	-0.12	0.2	-9999	-0.33	208	208
CXCR4	-0.12	0.19	-9999	-0.32	208	208
FLT1	0.003	0.016	-9999	-10000	0	0
RhoA/GDP	0.008	0	-9999	-10000	0	0
Rac1/GDP	0.008	0	-9999	-10000	0	0
SRC	-0.12	0.19	-9999	-0.32	208	208
S1P/S1P3/Gi	-0.13	0.2	-9999	-0.31	260	260
RAC1	0.011	0	-9999	-10000	0	0
RhoA/GTP	-0.12	0.18	-9999	-0.31	208	208
VEGFA	0.003	0.016	-9999	-10000	0	0
S1P/S1P2/Gi	-0.084	0.14	-9999	-0.26	154	154
VEGFR1 homodimer/VEGFA homodimer	0	0.031	-9999	-10000	0	0
RHOA	0.011	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.021	0.1	-9999	-0.25	75	75
GNAQ	0.009	0.026	-9999	-0.41	2	2
GNAZ	-0.007	0.069	-9999	-0.41	15	15
G12/G13	0.016	0	-9999	-10000	0	0
GNA14	-0.032	0.13	-9999	-0.41	55	55
GNA15	0.007	0.039	-9999	-0.33	7	7
GNA12	0.011	0	-9999	-10000	0	0
GNA13	0.011	0	-9999	-10000	0	0
GNA11	0.002	0.062	-9999	-0.41	12	12
Rac1/GTP	-0.12	0.18	-9999	-0.31	208	208

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.011	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.13	0.059	-9999	-0.32	3	3
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.038	0.014	-9999	-10000	0	0
AURKB	-0.29	0.11	-9999	-0.33	472	472
AURKC	0.009	0.025	-9999	-0.33	3	3

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.009	0.001	-10000	0	-10000	0	0
GNB1/GNG2	-0.022	0.09	-10000	0	-0.21	98	98
regulation of S phase of mitotic cell cycle	-0.017	0.087	-10000	0	-0.2	93	93
GNAO1	-0.1	0.18	-10000	0	-0.41	142	142
HRAS	0.01	0.002	-10000	0	-10000	0	0
SHBG/T-DHT	0.005	0.024	-10000	0	-0.24	5	5
PELP1	0.01	0.002	-10000	0	-10000	0	0
AKT1	0.009	0.001	-10000	0	-10000	0	0
MAP2K1	-0.031	0.092	-10000	0	-0.27	32	32
T-DHT/AR	-0.043	0.11	-10000	0	-0.29	90	90
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.002	0.003	-10000	0	-0.007	165	165
GNAI2	0.011	0	-10000	0	-10000	0	0
GNAI3	0.011	0	-10000	0	-10000	0	0
GNAI1	0.005	0.051	-10000	0	-0.41	8	8
mol:GDP	-0.058	0.13	-10000	0	-0.35	90	90
cell proliferation	-0.1	0.2	-10000	0	-0.38	165	165
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
FOS	-0.22	0.37	-10000	0	-0.77	165	165
mol:Ca2+	-0.024	0.029	-10000	0	-0.061	173	173
MAPK3	-0.07	0.15	-10000	0	-0.26	165	165
MAPK1	-0.049	0.1	-10000	0	-0.2	165	165
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
mol:IP3	-0.001	0.002	-10000	0	-0.004	165	165
cAMP biosynthetic process	0.008	0.03	0.092	6	-0.2	5	11
GNG2	0.003	0.056	-10000	0	-0.4	10	10
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.004	165	165
HRAS/GTP	-0.041	0.071	-10000	0	-0.19	90	90
actin cytoskeleton reorganization	-0.002	0.018	-10000	0	-0.18	6	6
SRC	0.01	0.002	-10000	0	-10000	0	0
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.004	165	165
PI3K	0.012	0.026	-10000	0	-0.23	6	6
apoptosis	0.11	0.2	0.4	165	-10000	0	165
T-DHT/AR/PELP1	-0.03	0.094	-10000	0	-0.24	90	90
HRAS/GDP	-0.055	0.13	-10000	0	-0.33	90	90
CREB1	-0.12	0.21	-10000	0	-0.43	165	165
RAC1-CDC42/GTP	-0.002	0.019	-10000	0	-0.18	6	6
AR	-0.061	0.16	-10000	0	-0.41	90	90
GNB1	0.011	0	-10000	0	-10000	0	0
RAF1	-0.027	0.085	-10000	0	-0.25	32	32
RAC1-CDC42/GDP	-0.048	0.12	-10000	0	-0.31	90	90
T-DHT/AR/PELP1/Src	-0.023	0.085	-10000	0	-0.21	90	90
MAP2K2	-0.031	0.092	-10000	0	-0.27	32	32
T-DHT/AR/PELP1/Src/PI3K	-0.017	0.088	-10000	0	-0.21	93	93
GNAZ	-0.001	0.069	-10000	0	-0.41	15	15
SHBG	0.007	0.04	-10000	0	-0.41	5	5
Gi family/GNB1/GNG2/GDP	-0.072	0.16	-10000	0	-0.32	145	145
mol:T-DHT	-0.001	0.001	-10000	0	-0.003	133	133
RAC1	0.011	0	-10000	0	-10000	0	0
GNRH1	0.005	0.031	-10000	0	-0.29	6	6
Gi family/GTP	-0.058	0.12	-10000	0	-0.21	154	154
CDC42	0.011	0	-10000	0	-10000	0	0

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.063	0.15	-9999	-0.25	161	161
FZD6	0.01	0.018	-9999	-0.41	1	1
WNT6	-0.03	0.12	-9999	-0.38	57	57
WNT4	-0.089	0.18	-9999	-0.41	128	128
FZD3	0.011	0	-9999	-10000	0	0
WNT5A	-0.002	0.074	-9999	-0.41	17	17
WNT11	-0.031	0.12	-9999	-0.35	63	63

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0.044	0.028	-9999	-10000	0	0
BUB1B	-0.06	0.051	-9999	-0.11	167	167
PLK1	-0.013	0.023	-9999	-10000	0	0
PLK1S1	-0.003	0.017	-9999	-0.26	1	1
KIF2A	-0.005	0.02	-9999	-10000	0	0
regulation of mitotic centrosome separation	-0.013	0.023	-9999	-10000	0	0
GOLGA2	0.011	0	-9999	-10000	0	0
Hec1/SPC24	-0.11	0.1	-9999	-0.18	339	339
WEE1	-0.008	0.023	-9999	-10000	0	0
cytokinesis	-0.079	0.043	-9999	-0.21	14	14
PP2A-alpha B56	0.037	0.005	-9999	-10000	0	0
AURKA	-0.005	0.014	-9999	-10000	0	0
PICH/PLK1	-0.08	0.11	-9999	-0.2	210	210
CENPE	-0.055	0.089	-9999	-0.19	159	159
RhoA/GTP	0.008	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	-0.005	0.02	-9999	-10000	0	0
PPP2CA	0.011	0	-9999	-10000	0	0
FZR1	0.011	0	-9999	-10000	0	0
TPX2	-0.016	0.015	-9999	-10000	0	0
PAK1	0.01	0.001	-9999	-10000	0	0
SPC24	-0.2	0.17	-9999	-0.33	329	329
FBXW11	0.011	0	-9999	-10000	0	0
CLSPN	-0.014	0.019	-9999	-10000	0	0
GORASP1	0.011	0	-9999	-10000	0	0
metaphase	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NLP	-0.008	0.013	-9999	-10000	0	0
G2 phase of mitotic cell cycle	-0.001	0.002	-9999	-10000	0	0
STAG2	0.011	0	-9999	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.012	0.007	-9999	-10000	0	0
spindle elongation	-0.013	0.023	-9999	-10000	0	0
ODF2	0.01	0.001	-9999	-10000	0	0
BUB1	0.023	0.011	-9999	-10000	0	0
TPT1	-0.003	0.013	-9999	-10000	0	0
CDC25C	-0.018	0.014	-9999	-10000	0	0
CDC25B	0.01	0.001	-9999	-10000	0	0
SGOL1	-0.044	0.028	-9999	-10000	0	0
RHOA	0.011	0	-9999	-10000	0	0
CCNB1/CDK1	-0.018	0.048	-9999	-10000	0	0
CDC14B	0.008	0.013	-9999	-0.3	1	1
CDC20	-0.29	0.11	-9999	-0.33	476	476
PLK1/PBIP1	-0.016	0.044	-9999	-0.18	32	32
mitosis	-0.004	0.007	-9999	-0.015	154	154
FBXO5	-0.005	0.02	-9999	-10000	0	0
CDC2	-0.001	0.002	-9999	-10000	0	0
NDC80	-0.014	0.088	-9999	-0.33	39	39
metaphase plate congression	-0.006	0.015	-9999	-10000	0	0
ERCC6L	-0.07	0.1	-9999	-0.21	131	131
NLP/gamma Tubulin	-0.005	0.013	-9999	-10000	0	0
microtubule cytoskeleton organization	-0.003	0.013	-9999	-10000	0	0
G2/M transition DNA damage checkpoint	-0.001	0.001	-9999	-10000	0	0
PPP1R12A	0.01	0.018	-9999	-0.41	1	1
interphase	-0.001	0.001	-9999	-10000	0	0
PLK1/PRC1-2	-0.15	0.069	-9999	-0.17	485	485
GRASP65/GM130/RAB1/GTP/PLK1	0.008	0.018	-9999	-10000	0	0
RAB1A	0.011	0	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
Aurora A/BORA	-0.006	0.022	-9999	-10000	0	0
mitotic prometaphase	-0.002	0.001	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.013	0.018	-9999	-0.19	1	1
microtubule-based process	-0.16	0.06	-9999	-0.18	485	485
Golgi organization	-0.013	0.023	-9999	-10000	0	0
Cohesin/SA2	-0.013	0.014	-9999	-10000	0	0
PPP1CB/MYPT1	0.015	0.013	-9999	-0.28	1	1
KIF20A	-0.3	0.1	-9999	-0.33	485	485
APC/C/CDC20	-0.16	0.065	-9999	-0.18	476	476
PPP2R1A	0.011	0	-9999	-10000	0	0
chromosome segregation	-0.019	0.042	-9999	-0.18	32	32
PRC1	-0.004	0.069	-9999	-0.33	23	23
ECT2	-0.016	0.05	-9999	-0.19	34	34
C13orf34	-0.005	0.02	-9999	-10000	0	0
NUDC	-0.006	0.015	-9999	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.06	0.05	-9999	-0.11	167	167
spindle assembly	-0.008	0.018	-9999	-10000	0	0
spindle stabilization	-0.003	0.017	-9999	-0.26	1	1
APC/C/HCDH1	0.014	0.011	-9999	-0.24	1	1
MKLP2/PLK1	-0.16	0.06	-9999	-0.18	485	485
CCNB1	-0.048	0.13	-9999	-0.33	93	93
PPP1CB	0.011	0.001	-9999	-10000	0	0
BTRC	0.011	0	-9999	-10000	0	0
ROCK2	-0.009	0.065	-9999	-0.4	14	14
TUBG1	-0.003	0.013	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.026	0.043	-9999	-10000	0	0
MLF1IP	-0.011	0.056	-9999	-0.23	32	32
INCENP	0.01	0.001	-9999	-10000	0	0

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.08	0.31	-9999	-0.95	59	59
MKNK1	0.011	0	-9999	-10000	0	0
MAPK14	-0.013	0.097	-9999	-0.27	66	66
ATF2/c-Jun	-0.003	0.1	-9999	-0.61	7	7
MAPK11	-0.015	0.1	-9999	-0.27	68	68
MITF	-0.041	0.16	-9999	-0.34	110	110
MAPKAPK5	-0.009	0.12	-9999	-0.32	68	68
KRT8	-0.026	0.13	-9999	-0.34	70	70
MAPKAPK3	0.011	0	-9999	-10000	0	0
MAPKAPK2	0.011	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.021	0.14	-9999	-0.39	68	68
CEBPB	-0.009	0.12	-9999	-0.32	68	68
SLC9A1	-0.009	0.12	-9999	-0.32	68	68
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.007	0.12	-9999	-0.31	71	71
p38alpha-beta/MNK1	-0.006	0.11	-9999	-0.3	66	66
JUN	-0.003	0.1	-9999	-0.61	7	7
PPARGC1A	-0.073	0.18	-9999	-0.32	161	161
USF1	-0.009	0.12	-9999	-0.32	68	68
RAB5/GDP/GDI1	-0.029	0.074	-9999	-0.22	66	66
NOS2	-0.019	0.16	-9999	-0.78	11	11
DDIT3	-0.009	0.12	-9999	-0.32	68	68
RAB5A	0.011	0	-9999	-10000	0	0
HSPB1	-0.001	0.096	-9999	-0.25	66	66
p38alpha-beta/HBP1	-0.006	0.11	-9999	-0.3	66	66
CREB1	-0.011	0.13	-9999	-0.34	68	68
RAB5/GDP	0.008	0	-9999	-10000	0	0
EIF4E	-0.001	0.099	-9999	-0.26	66	66
RPS6KA4	-0.009	0.12	-9999	-0.32	68	68
PLA2G4A	-0.014	0.12	-9999	-0.31	67	67
GDI1	-0.009	0.12	-9999	-0.32	68	68
TP53	-0.016	0.14	-9999	-0.39	68	68
RPS6KA5	-0.013	0.12	-9999	-0.32	73	73
ESR1	-0.045	0.17	-9999	-0.35	113	113
HBP1	0.011	0	-9999	-10000	0	0
MEF2C	-0.04	0.16	-9999	-0.34	107	107
MEF2A	-0.013	0.13	-9999	-0.33	72	72
EIF4EBP1	-0.011	0.13	-9999	-0.34	68	68
KRT19	-0.014	0.12	-9999	-0.32	72	72
ELK4	-0.009	0.12	-9999	-0.32	68	68
ATF6	-0.009	0.12	-9999	-0.32	68	68
ATF1	-0.011	0.13	-9999	-0.34	68	68
p38alpha-beta/MAPKAPK2	-0.006	0.11	-9999	-0.3	66	66
p38alpha-beta/MAPKAPK3	-0.006	0.11	-9999	-0.3	66	66

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.016	0.01	-9999	-0.22	1	1
VLDLR	0.009	0.026	-9999	-0.41	2	2
CRKL	0.011	0	-9999	-10000	0	0
LRPAP1	0.011	0	-9999	-10000	0	0
FYN	0.011	0	-9999	-10000	0	0
ITGA3	0.01	0.018	-9999	-0.41	1	1
RELN/VLDLR/Fyn	-0.07	0.12	-9999	-0.23	199	199
MAPK8IP1/MKK7/MAP3K11/JNK1	0.03	0.025	-9999	-10000	0	0
AKT1	-0.052	0.1	-9999	-0.25	3	3
MAP2K7	0.011	0	-9999	-10000	0	0
RAPGEF1	0.011	0	-9999	-10000	0	0
DAB1	-0.001	0.052	-9999	-0.33	13	13
RELN/LRP8/DAB1	-0.07	0.11	-9999	-0.2	212	212
LRPAP1/LRP8	0.014	0.022	-9999	-0.22	5	5
RELN/LRP8/DAB1/Fyn	-0.059	0.1	-9999	-0.19	193	193
DAB1/alpha3/beta1 Integrin	-0.062	0.08	-9999	-0.33	5	5
long-term memory	-0.13	0.15	-9999	-0.36	106	106
DAB1/LIS1	-0.066	0.083	-9999	-0.31	5	5
DAB1/CRLK/C3G	-0.062	0.078	-9999	-0.3	5	5
PIK3CA	0.01	0.018	-9999	-0.41	1	1
DAB1/NCK2	-0.066	0.084	-9999	-0.31	5	5
ARHGEF2	0.011	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.15	0.2	-9999	-0.41	210	210
CDK5R1	0.01	0.015	-9999	-0.33	1	1
RELN	-0.14	0.2	-9999	-0.41	198	198
PIK3R1	0.007	0.04	-9999	-0.41	5	5
RELN/LRP8/Fyn	-0.071	0.12	-9999	-0.23	200	200
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.13	0.15	-9999	-0.25	311	311
MAPK8	0.006	0.044	-9999	-0.41	6	6
RELN/VLDLR/DAB1	-0.069	0.11	-9999	-0.21	195	195
ITGB1	0.011	0	-9999	-10000	0	0
MAP1B	-0.069	0.11	-9999	-0.2	212	212
RELN/LRP8	-0.071	0.12	-9999	-0.23	200	200
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.062	0.11	-9999	-0.2	135	135
PI3K	0.013	0.031	-9999	-0.28	6	6
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	0.016	0.013	-9999	-0.28	1	1
RAP1A	-0.032	0.092	-9999	-0.28	5	5
PAFAH1B1	0.011	0	-9999	-10000	0	0
MAPK8IP1	0.01	0.023	-9999	-0.37	2	2
CRLK/C3G	0.016	0	-9999	-10000	0	0
GRIN2B	-0.007	0.065	-9999	-0.33	21	21
NCK2	0.011	0	-9999	-10000	0	0
neuron differentiation	-0.031	0.083	-9999	-0.25	3	3
neuron adhesion	-0.021	0.09	-9999	-0.29	5	5
LRP8	0.008	0.033	-9999	-0.33	5	5
GSK3B	-0.044	0.096	-9999	-0.36	1	1
RELN/VLDLR/DAB1/Fyn	-0.058	0.1	-9999	-0.19	193	193
MAP3K11	0.011	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.062	0.11	-9999	-0.2	198	198
CDK5	0.011	0	-9999	-10000	0	0
MAPT	0.002	0.076	-9999	-0.37	20	20
neuron migration	-0.051	0.13	-9999	-0.23	80	80
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.031	0.083	-9999	-0.25	3	3
RELN/VLDLR	-0.057	0.11	-9999	-0.2	193	193

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.009	0.01	-9999	-0.23	1	1
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	0.011	0.022	-9999	-0.22	5	5
STXBP1	-0.017	0.1	-9999	-0.41	36	36
ACh/CHRNA1	-0.098	0.1	-9999	-0.23	193	193
RAB3GAP2/RIMS1/UNC13B	0.018	0.019	-9999	-0.17	5	5
mol:Ca2+	0	0	-9999	-10000	0	0
UniProt:P30996	0	0	-9999	-10000	0	0
UniProt:Q60393	0	0	-9999	-10000	0	0
CST086	0	0	-9999	-10000	0	0
RIMS1	0.003	0.033	-9999	-0.33	5	5
mol:ACh	-0.043	0.056	-9999	-0.1	244	244
RAB3GAP2	0.011	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.062	0.075	-9999	-0.28	28	28
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.098	0.1	-9999	-0.23	193	193
UNC13B	0.011	0	-9999	-10000	0	0
CHRNA1	-0.11	0.16	-9999	-0.33	193	193
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.082	0.12	-9999	-0.3	119	119
SNAP25	-0.11	0.13	-9999	-0.25	244	244
VAMP2	0.005	0	-9999	-10000	0	0
SYT1	-0.082	0.17	-9999	-0.41	119	119
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.002	0.063	-9999	-0.23	37	37
STX1A/SNAP25 fragment 1/VAMP2	-0.062	0.075	-9999	-0.28	28	28

×

LPA4-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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.005	0.049	-9999	-0.23	22	22
ADCY5	-0.03	0.096	-9999	-0.23	98	98
ADCY6	0.015	0	-9999	-10000	0	0
ADCY7	0.015	0	-9999	-10000	0	0
ADCY1	0.002	0.053	-9999	-0.22	30	30
ADCY2	-0.12	0.12	-9999	-0.23	297	297
ADCY3	0.014	0.015	-9999	-0.23	2	2
ADCY8	0.008	0.019	-9999	-0.18	5	5
PRKCE	0.009	0	-9999	-10000	0	0
ADCY9	-0.018	0.085	-9999	-0.23	72	72
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.06	0.078	-9999	-0.17	127	127

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.11	0.12	-9999	-0.23	291	291
fibroblast growth factor receptor signaling pathway	-0.11	0.12	-9999	-0.23	291	291
LAMA1	-0.1	0.16	-9999	-0.33	182	182
PRNP	-0.047	0.14	-9999	-0.41	74	74
GPC1/SLIT2	-0.021	0.098	-9999	-0.28	68	68
SMAD2	0.022	0.033	-9999	-0.2	12	12
GPC1/PrPc/Cu2+	-0.019	0.086	-9999	-0.23	74	74
GPC1/Laminin alpha1	-0.063	0.11	-9999	-0.22	182	182
TDGF1	-0.02	0.1	-9999	-0.38	42	42
CRIPTO/GPC1	-0.005	0.073	-9999	-0.26	42	42
APP/GPC1	0.016	0	-9999	-10000	0	0
mol:NO	0	0	-9999	-10000	0	0
YES1	0.004	0.061	-9999	-0.2	42	42
FLT1	0.011	0	-9999	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	0.017	0.037	-9999	-0.23	12	12
SERPINC1	0.004	0.039	-9999	-0.33	7	7
FYN	0.004	0.061	-9999	-0.2	42	42
FGR	-0.001	0.072	-9999	-0.22	52	52
positive regulation of MAPKKK cascade	0.014	0.073	-9999	-0.27	27	27
SLIT2	-0.042	0.14	-9999	-0.41	68	68
GPC1/NRG	0.005	0.057	-9999	-0.28	21	21
NRG1	-0.006	0.081	-9999	-0.41	21	21
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.022	0	-9999	-10000	0	0
LYN	0.004	0.061	-9999	-0.2	42	42
mol:Spermine	0.009	0	-9999	-10000	0	0
cell growth	-0.11	0.12	-9999	-0.23	291	291
BMP signaling pathway	-0.011	0	-9999	-10000	0	0
SRC	0.004	0.061	-9999	-0.2	42	42
TGFBR1	0.011	0	-9999	-10000	0	0
mol:Cu2+	0	0	-9999	-10000	0	0
PLA2G2A	-0.033	0.12	-9999	-0.39	55	55
GPC1	0.011	0	-9999	-10000	0	0
TGFBR1 (dimer)	0.011	0	-9999	-10000	0	0
VEGFA	0.011	0	-9999	-10000	0	0
BLK	-0.011	0.077	-9999	-0.2	78	78
HCK	0.002	0.064	-9999	-0.2	49	49
FGF2	-0.22	0.21	-9999	-0.41	291	291
FGFR1	0.01	0.018	-9999	-0.41	1	1
VEGFR1 homodimer	0.011	0	-9999	-10000	0	0
TGFBR2	0.002	0.062	-9999	-0.41	12	12
cell death	0.016	0	-9999	-10000	0	0
ATIII/GPC1	0.012	0.027	-9999	-0.22	7	7
PLA2G2A/GPC1	-0.014	0.086	-9999	-0.27	55	55
LCK	0.002	0.065	-9999	-0.21	46	46
neuron differentiation	0.005	0.057	-9999	-0.28	21	21
PrPc/Cu2+	-0.032	0.1	-9999	-0.29	74	74
APP	0.011	0	-9999	-10000	0	0
TGFBR2 (dimer)	0.002	0.062	-9999	-0.41	12	12

×

IGF1 pathway

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
NCK2	0.011	0	-10000	0	-10000	0	0
PTK2	0.011	0	-10000	0	-10000	0	0
CRKL	-0.041	0.12	-10000	0	-0.25	111	111
GRB2/SOS1/SHC	0.022	0	-10000	0	-10000	0	0
HRAS	0.011	0	-10000	0	-10000	0	0
IRS1/Crk	-0.041	0.12	-10000	0	-0.25	111	111
IGF-1R heterotetramer/IGF1/PTP1B	-0.035	0.11	-10000	0	-0.25	111	111
AKT1	-0.021	0.11	-10000	0	-0.32	38	38
BAD	-0.014	0.1	-10000	0	-0.3	38	38
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.041	0.12	-10000	0	-0.25	111	111
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.041	0.12	-10000	0	-0.25	111	111
RAF1	-0.009	0.099	-10000	0	-0.41	5	5
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.032	0.12	-10000	0	-0.24	111	111
YWHAZ	0.011	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.051	0.13	-10000	0	-0.26	135	135
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
RPS6KB1	-0.021	0.11	-10000	0	-0.32	38	38
GNB2L1	0.011	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.01	0.087	-10000	0	-0.25	38	38
PXN	0.011	0	-10000	0	-10000	0	0
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.016	0	-10000	0	-10000	0	0
HRAS/GTP	-0.046	0.091	-10000	0	-0.32	37	37
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.012	0.092	-10000	0	-0.24	37	37
IGF-1R heterotetramer	-0.02	0.093	-10000	0	-0.46	21	21
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.04	0.12	-10000	0	-0.25	111	111
Crk/p130 Cas/Paxillin	-0.025	0.11	-10000	0	-0.34	37	37
IGF1R	-0.02	0.093	-10000	0	-0.46	21	21
IGF1	-0.076	0.18	-10000	0	-0.44	101	101
IRS2/Crk	-0.059	0.14	-10000	0	-0.25	161	161
PI3K	-0.034	0.12	-10000	0	-0.24	114	114
apoptosis	0.006	0.091	0.26	38	-10000	0	38
HRAS/GDP	0.008	0	-10000	0	-10000	0	0
PRKCD	-0.047	0.16	-10000	0	-0.34	106	106
RAF1/14-3-3 E	-0.002	0.089	-10000	0	-0.35	5	5
BAD/14-3-3	-0.007	0.096	-10000	0	-0.28	38	38
PRKCZ	-0.022	0.11	-10000	0	-0.32	38	38
Crk/p130 Cas/Paxillin/FAK1	-0.038	0.077	-10000	0	-0.27	38	38
PTPN1	0.011	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.055	0.16	-10000	0	-0.36	111	111
BCAR1	0.011	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.022	0.1	-10000	0	-0.21	112	112
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.011	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.041	0.12	-10000	0	-0.25	111	111
GRB10	0.01	0.018	-10000	0	-0.41	1	1
PTPN11	-0.041	0.12	-10000	0	-0.25	111	111
IRS1	-0.046	0.13	-10000	0	-0.28	111	111
IRS2	-0.068	0.14	-10000	0	-0.27	161	161
IGF-1R heterotetramer/IGF1	-0.06	0.15	-10000	0	-0.34	111	111
GRB2	0.011	0	-10000	0	-10000	0	0
PDPK1	-0.028	0.11	-10000	0	-0.33	41	41
YWHAE	0.011	0	-10000	0	-10000	0	0
PRKD1	-0.06	0.17	-10000	0	-0.36	115	115
SHC1	0.011	0	-10000	0	-10000	0	0

×

Aurora A 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	-0.012	0.043	-9999	-10000	0	0
BIRC5	-0.25	0.14	-9999	-0.33	416	416
NFKBIA	-0.013	0.042	-9999	-10000	0	0
CPEB1	-0.17	0.21	-9999	-0.41	233	233
AKT1	-0.013	0.042	-9999	-10000	0	0
NDEL1	0.011	0	-9999	-10000	0	0
Aurora A/BRCA1	-0.011	0.038	-9999	-10000	0	0
NDEL1/TACC3	-0.04	0.09	-9999	-0.22	83	83
GADD45A	0.011	0	-9999	-10000	0	0
GSK3B	0.007	0.001	-9999	-10000	0	0
PAK1/Aurora A	-0.012	0.043	-9999	-10000	0	0
MDM2	0.011	0	-9999	-10000	0	0
JUB	0.011	0	-9999	-10000	0	0
TPX2	-0.17	0.093	-9999	-0.22	436	436
TP53	0	0.029	-9999	-0.28	1	1
DLG7	-0.021	0.042	-9999	-10000	0	0
AURKAIP1	0.011	0	-9999	-10000	0	0
ARHGEF7	0.011	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	-0.043	0.096	-9999	-0.23	83	83
G2/M transition of mitotic cell cycle	-0.011	0.038	-9999	-10000	0	0
AURKA	-0.024	0.053	-9999	-10000	0	0
AURKB	-0.014	0.013	-9999	-10000	0	0
CDC25B	-0.005	0.033	-9999	-10000	0	0
G2/M transition checkpoint	-0.011	0.038	-9999	-10000	0	0
mRNA polyadenylation	-0.11	0.12	-9999	-0.23	233	233
Aurora A/CPEB	-0.11	0.12	-9999	-0.23	233	233
Aurora A/TACC1/TRAP/chTOG	-0.034	0.092	-9999	-0.22	91	91
BRCA1	0.011	0	-9999	-10000	0	0
centrosome duplication	-0.012	0.043	-9999	-10000	0	0
regulation of centrosome cycle	-0.04	0.089	-9999	-0.22	83	83
spindle assembly	-0.035	0.091	-9999	-0.21	91	91
TDRD7	0.011	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.12	0.087	-9999	-0.21	164	164
CENPA	-0.003	0.016	-9999	-10000	0	0
Aurora A/PP2A	-0.012	0.043	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.002	0.028	-9999	-10000	0	0
negative regulation of DNA binding	0	0.029	-9999	-0.28	1	1
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0.016	0	-9999	-10000	0	0
RASA1	0.007	0.04	-9999	-0.41	5	5
Ajuba/Aurora A	-0.011	0.038	-9999	-10000	0	0
mitotic prometaphase	-0.02	0.008	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.024	0.053	-9999	-10000	0	0
TACC1	-0.066	0.16	-9999	-0.41	98	98
TACC3	-0.067	0.14	-9999	-0.33	123	123
Aurora A/Antizyme1	-0.003	0.038	-9999	-10000	0	0
Aurora A/RasGAP	-0.014	0.048	-9999	-0.24	5	5
OAZ1	0.011	0	-9999	-10000	0	0
RAN	0.011	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.007	0.001	-9999	-10000	0	0
GIT1	0.011	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0.022	0	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.17	0.092	-9999	-0.22	436	436
PPP2R5D	0.011	0	-9999	-10000	0	0
Aurora A/TPX2	-0.15	0.088	-9999	-0.23	159	159
PAK1	0.011	0	-9999	-10000	0	0
CKAP5	0.011	0	-9999	-10000	0	0

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.009	0.031	-9999	-0.41	3	3
LAT2	-0.066	0.13	-9999	-0.23	167	167
AP1	-0.12	0.14	-9999	-0.35	104	104
mol:PIP3	-0.067	0.15	-9999	-0.4	38	38
IKBKB	-0.035	0.097	-9999	-0.22	51	51
AKT1	-0.03	0.1	-9999	-0.28	40	40
IKBKG	-0.035	0.097	-9999	-0.22	51	51
MS4A2	-0.12	0.19	-9999	-0.4	166	166
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.01	0.018	-9999	-0.41	1	1
MAP3K1	-0.042	0.12	-9999	-0.31	37	37
mol:Ca2+	-0.05	0.12	-9999	-0.31	38	38
LYN	0.01	0.003	-9999	-10000	0	0
CBLB	-0.065	0.13	-9999	-0.23	167	167
SHC1	0.011	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.035	0.1	-9999	-0.21	131	131
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0.01	0.018	-9999	-0.41	1	1
PLD2	-0.057	0.12	-9999	-0.34	38	38
PTPN13	-0.091	0.15	-9999	-0.38	65	65
PTPN11	0.01	0.005	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.029	0.11	-9999	-0.26	40	40
SYK	0.01	0.015	-9999	-0.33	1	1
GRB2	0.011	0.001	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.098	0.13	-9999	-0.41	38	38
LAT	-0.065	0.13	-9999	-0.23	167	167
PAK2	-0.052	0.13	-9999	-0.34	37	37
NFATC2	-0.08	0.16	-9999	-0.53	53	53
HRAS	-0.062	0.14	-9999	-0.37	37	37
GAB2	0.008	0.036	-9999	-0.41	4	4
PLA2G1B	0.028	0.015	-9999	-10000	0	0
Fc epsilon R1	-0.1	0.14	-9999	-0.25	220	220
Antigen/IgE/Fc epsilon R1	-0.09	0.12	-9999	-0.22	220	220
mol:GDP	-0.07	0.14	-9999	-0.39	38	38
JUN	0.006	0.048	-9999	-0.41	7	7
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.007	0.04	-9999	-0.41	5	5
FOS	-0.12	0.19	-9999	-0.41	165	165
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.075	0.13	-9999	-0.25	169	169
CHUK	-0.035	0.097	-9999	-0.22	51	51
KLRG1	-0.056	0.11	-9999	-0.32	38	38
VAV1	-0.067	0.13	-9999	-0.23	167	167
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.065	0.13	-9999	-0.23	167	167
negative regulation of mast cell degranulation	-0.047	0.1	-9999	-0.3	36	36
BTK	-0.075	0.14	-9999	-0.4	38	38
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.076	0.15	-9999	-0.31	91	91
GAB2/PI3K/SHP2	-0.063	0.089	-9999	-0.31	40	40
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.064	0.13	-9999	-0.4	38	38
RAF1	0.019	0.018	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.081	0.11	-9999	-0.36	41	41
FCER1G	0.016	0.024	-9999	-0.33	2	2
FCER1A	-0.061	0.16	-9999	-0.42	88	88
Antigen/IgE/Fc epsilon R1/Fyn	-0.081	0.11	-9999	-0.26	88	88
MAPK3	0.027	0.015	-9999	-10000	0	0
MAPK1	0.027	0.015	-9999	-10000	0	0
NFKB1	0.01	0.018	-9999	-0.41	1	1
MAPK8	-0.011	0.077	-9999	-0.55	7	7
DUSP1	-0.091	0.18	-9999	-0.41	130	130
NF-kappa-B/RelA	-0.036	0.046	-9999	-0.18	6	6
actin cytoskeleton reorganization	-0.076	0.14	-9999	-0.39	37	37
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.08	0.11	-9999	-0.34	40	40
FER	-0.065	0.13	-9999	-0.23	167	167
RELA	0.011	0	-9999	-10000	0	0
ITK	-0.032	0.062	-9999	-0.36	14	14
SOS1	0.011	0	-9999	-10000	0	0
PLCG1	-0.067	0.14	-9999	-0.4	37	37
cytokine secretion	-0.027	0.034	-9999	-10000	0	0
SPHK1	-0.065	0.13	-9999	-0.23	167	167
PTK2	-0.079	0.15	-9999	-0.4	37	37
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.1	0.13	-9999	-0.27	169	169
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.064	0.15	-9999	-0.4	39	39
MAP2K2	0.023	0.015	-9999	-10000	0	0
MAP2K1	0.023	0.015	-9999	-10000	0	0
MAP2K7	0.011	0	-9999	-10000	0	0
KLRG1/SHP2	-0.057	0.087	-9999	-0.29	36	36
MAP2K4	0.012	0.038	-9999	-0.84	1	1
Fc epsilon R1/FcgammaRIIB	-0.09	0.12	-9999	-0.29	90	90
mol:Choline	-0.056	0.11	-9999	-0.33	38	38
SHC/Grb2/SOS1	-0.069	0.11	-9999	-0.33	35	35
FYN	0.011	0	-9999	-10000	0	0
DOK1	0.011	0	-9999	-10000	0	0
PXN	-0.069	0.14	-9999	-0.38	35	35
HCLS1	-0.065	0.13	-9999	-0.23	168	168
PRKCB	-0.056	0.13	-9999	-0.31	53	53
FCGR2B	0.008	0.035	-9999	-0.39	4	4
IGHE	-0.001	0.004	-9999	-10000	0	0
KLRG1/SHIP	-0.048	0.11	-9999	-0.3	36	36
LCP2	0.01	0.015	-9999	-0.33	1	1
PLA2G4A	-0.076	0.14	-9999	-0.24	174	174
RASA1	0.007	0.04	-9999	-0.41	5	5
mol:Phosphatidic acid	-0.056	0.11	-9999	-0.33	38	38
IKK complex	-0.016	0.078	-9999	-0.16	51	51
WIPF1	0.009	0.026	-9999	-0.41	2	2

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.1	0.18	-9999	-0.41	142	142
CDC42/GTP	-0.03	0.1	-9999	-0.18	144	144
PLCG1	-0.031	0.1	-9999	-0.19	144	144
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.011	0	-9999	-10000	0	0
GNAI3	0.011	0	-9999	-10000	0	0
G12/G13	0.016	0	-9999	-10000	0	0
cell migration	-0.03	0.098	-9999	-0.18	144	144
S1PR5	0	0.063	-9999	-0.35	17	17
S1PR4	0.009	0.029	-9999	-0.38	3	3
MAPK3	-0.031	0.1	-9999	-0.19	144	144
MAPK1	-0.031	0.1	-9999	-0.19	144	144
S1P/S1P5/Gi	-0.042	0.11	-9999	-0.21	156	156
GNAI1	0.005	0.051	-9999	-0.41	8	8
CDC42/GDP	0.008	0	-9999	-10000	0	0
S1P/S1P5/G12	0.008	0.037	-9999	-0.19	17	17
RHOA	0.024	0.015	-9999	-0.18	2	2
S1P/S1P4/Gi	-0.039	0.11	-9999	-0.21	154	154
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.001	0.069	-9999	-0.41	15	15
S1P/S1P4/G12/G13	0.02	0.016	-9999	-0.19	3	3
GNA12	0.011	0	-9999	-10000	0	0
GNA13	0.011	0	-9999	-10000	0	0
CDC42	0.011	0	-9999	-10000	0	0

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.032	0.1	0.18	145	-10000	0	145
GNAI2	0.011	0	-10000	0	-10000	0	0
S1P/S1P5/G12	0.008	0.037	-10000	0	-0.19	17	17
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.1	0.18	-10000	0	-0.41	142	142
RhoA/GTP	-0.033	0.1	-10000	0	-0.19	145	145
negative regulation of cAMP metabolic process	-0.042	0.11	-10000	0	-0.21	156	156
GNAZ	-0.001	0.069	-10000	0	-0.41	15	15
GNAI3	0.011	0	-10000	0	-10000	0	0
GNA12	0.011	0	-10000	0	-10000	0	0
S1PR5	0	0.063	-10000	0	-0.35	17	17
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.042	0.11	-10000	0	-0.21	156	156
RhoA/GDP	0.008	0	-10000	0	-10000	0	0
RHOA	0.011	0	-10000	0	-10000	0	0
GNAI1	0.005	0.051	-10000	0	-0.41	8	8

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.031	0.12	-9999	-0.41	53	53
GNB1/GNG2	-0.049	0.14	-9999	-0.4	41	41
mol:DAG	-0.04	0.13	-9999	-0.37	41	41
PLCG1	-0.041	0.13	-9999	-0.38	41	41
YES1	-0.053	0.14	-9999	-0.42	38	38
FZD3	0.011	0	-9999	-10000	0	0
FZD6	0.01	0.018	-9999	-0.41	1	1
G protein	-0.041	0.13	-9999	-0.38	41	41
MAP3K7	-0.12	0.14	-9999	-0.33	122	122
mol:Ca2+	-0.038	0.12	-9999	-0.36	41	41
mol:IP3	-0.04	0.13	-9999	-0.37	41	41
NLK	-0.005	0.009	-9999	-10000	0	0
GNB1	0.011	0	-9999	-10000	0	0
CAMK2A	-0.14	0.15	-9999	-0.34	141	141
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.063	0.15	-9999	-0.25	161	161
CSNK1A1	0.011	0	-9999	-10000	0	0
GNAS	-0.053	0.14	-9999	-0.42	38	38
GO:0007205	-0.039	0.13	-9999	-0.36	41	41
WNT6	-0.03	0.12	-9999	-0.38	57	57
WNT4	-0.089	0.18	-9999	-0.41	128	128
NFAT1/CK1 alpha	-0.051	0.14	-9999	-0.41	43	43
GNG2	0.003	0.056	-9999	-0.4	10	10
WNT5A	-0.002	0.074	-9999	-0.41	17	17
WNT11	-0.031	0.12	-9999	-0.35	63	63
CDC42	-0.045	0.13	-9999	-0.4	38	38

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	-0.036	0.13	-10000	0	-0.38	64	64
NFATC2	-0.022	0.18	-10000	0	-0.51	45	45
NFATC3	-0.015	0.083	-10000	0	-0.26	27	27
CD40LG	-0.17	0.33	-10000	0	-0.86	78	78
ITCH	0.026	0.038	-10000	0	-10000	0	0
CBLB	0.026	0.038	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.14	0.25	-10000	0	-0.72	53	53
JUNB	0.007	0.04	-10000	0	-0.41	5	5
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.01	0.037	-10000	0	-0.23	1	1
T cell anergy	0.015	0.06	-10000	0	-0.27	3	3
TLE4	-0.031	0.21	-10000	0	-0.59	60	60
Jun/NFAT1-c-4/p21SNFT	-0.093	0.33	-10000	0	-0.8	85	85
AP-1/NFAT1-c-4	-0.17	0.39	-10000	0	-0.97	80	80
IKZF1	0.003	0.13	-10000	0	-0.42	26	26
T-helper 2 cell differentiation	-0.081	0.23	-10000	0	-0.77	33	33
AP-1/NFAT1	-0.082	0.18	-10000	0	-0.37	97	97
CALM1	0.015	0.026	-10000	0	-10000	0	0
EGR2	-0.11	0.4	-10000	0	-1.1	58	58
EGR3	-0.14	0.46	-10000	0	-1.2	81	81
NFAT1/FOXP3	-0.044	0.16	-10000	0	-0.38	61	61
EGR1	-0.045	0.14	-10000	0	-0.41	70	70
JUN	0	0.05	-10000	0	-0.41	7	7
EGR4	-0.003	0.058	-10000	0	-0.34	15	15
mol:Ca2+	0.003	0.028	-10000	0	-0.15	1	1
GBP3	0	0.14	-10000	0	-0.48	26	26
FOSL1	-0.014	0.089	-10000	0	-0.33	40	40
NFAT1-c-4/MAF/IRF4	-0.12	0.35	-10000	0	-0.85	86	86
DGKA	0.005	0.12	-10000	0	-0.42	22	22
CREM	0.011	0.001	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.1	0.34	-10000	0	-0.83	85	85
CTLA4	-0.042	0.16	-10000	0	-0.42	47	47
NFAT1-c-4 (dimer)/EGR1	-0.12	0.36	-10000	0	-0.88	85	85
NFAT1-c-4 (dimer)/EGR4	-0.1	0.34	-10000	0	-0.82	85	85
FOS	-0.12	0.19	-10000	0	-0.41	165	165
IFNG	-0.076	0.19	-10000	0	-0.65	30	30
T cell activation	-0.083	0.21	-10000	0	-0.63	42	42
MAF	-0.067	0.16	-10000	0	-0.41	100	100
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.08	0.3	0.72	85	-10000	0	85
TNF	-0.13	0.33	-10000	0	-0.79	88	88
FASLG	-0.16	0.47	-10000	0	-1.2	83	83
TBX21	0.002	0.062	-10000	0	-0.4	12	12
BATF3	0.01	0.015	-10000	0	-0.33	1	1
PRKCQ	-0.024	0.12	-10000	0	-0.41	48	48
PTPN1	0.005	0.12	-10000	0	-0.38	31	31
NFAT1-c-4/ICER1	-0.095	0.33	-10000	0	-0.81	85	85
GATA3	-0.002	0.069	-10000	0	-0.35	20	20
T-helper 1 cell differentiation	-0.063	0.2	-10000	0	-0.64	30	30
IL2RA	-0.13	0.25	-10000	0	-0.68	62	62
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	0.005	0.12	-10000	0	-0.41	24	24
E2F1	-0.048	0.13	-10000	0	-0.32	101	101
PPARG	-0.012	0.096	-10000	0	-0.41	30	30
SLC3A2	0.005	0.12	-10000	0	-0.42	22	22
IRF4	-0.002	0.071	-10000	0	-0.37	19	19
PTGS2	-0.18	0.35	-10000	0	-0.85	89	89
CSF2	-0.17	0.33	-10000	0	-0.85	78	78
JunB/Fra1/NFAT1-c-4	-0.094	0.32	-10000	0	-0.79	85	85
IL4	-0.085	0.24	-10000	0	-0.84	30	30
IL5	-0.17	0.32	-10000	0	-0.85	77	77
IL2	-0.084	0.21	-10000	0	-0.65	39	39
IL3	-0.037	0.048	-10000	0	-10000	0	0
RNF128	0.012	0.08	-10000	0	-0.26	43	43
NFATC1	-0.08	0.3	-10000	0	-0.72	85	85
CDK4	0.041	0.18	0.55	24	-10000	0	24
PTPRK	0.004	0.13	-10000	0	-0.43	22	22
IL8	-0.2	0.34	-10000	0	-0.85	83	83
POU2F1	0.011	0	-10000	0	-10000	0	0

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.011	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.054	0.089	-10000	0	-0.25	35	35
NT3 (dimer)/TRKC	-0.14	0.17	-10000	0	-0.3	264	264
NT3 (dimer)/TRKB	-0.11	0.16	-10000	0	-0.28	233	233
SHC/Grb2/SOS1/GAB1/PI3K	0.026	0.03	-10000	0	-0.19	10	10
RAPGEF1	0.011	0	-10000	0	-10000	0	0
BDNF	-0.042	0.12	-10000	0	-0.33	84	84
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
DYNLT1	0.011	0	-10000	0	-10000	0	0
NTRK1	0.001	0.058	-10000	0	-0.37	13	13
NTRK2	-0.042	0.14	-10000	0	-0.4	69	69
NTRK3	-0.19	0.21	-10000	0	-0.41	252	252
NT-4/5 (dimer)/TRKB	-0.1	0.15	-10000	0	-0.27	212	212
neuron apoptosis	0.14	0.19	0.39	156	-10000	0	156
SHC 2-3/Grb2	-0.15	0.21	-10000	0	-0.42	156	156
SHC1	0.011	0	-10000	0	-10000	0	0
SHC2	-0.18	0.24	0.17	1	-0.51	151	152
SHC3	-0.12	0.16	0.17	1	-0.4	99	100
STAT3 (dimer)	0.017	0.011	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	-0.084	0.14	-10000	0	-0.25	201	201
RIN/GDP	-0.043	0.08	-10000	0	-0.2	22	22
GIPC1	0.011	0	-10000	0	-10000	0	0
KRAS	0.01	0.015	-10000	0	-0.33	1	1
DNAJA3	-0.13	0.16	0.2	2	-0.32	183	185
RIN/GTP	0.002	0.003	-10000	0	-10000	0	0
CCND1	0.023	0.018	-10000	0	-0.22	3	3
MAGED1	0.009	0.026	-10000	0	-0.41	2	2
PTPN11	0.011	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.007	0.071	-10000	0	-0.33	24	24
SHC/GRB2/SOS1	0.022	0	-10000	0	-10000	0	0
GRB2	0.011	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.042	0.11	-10000	0	-0.24	129	129
TRKA/NEDD4-2	0.009	0.042	-10000	0	-0.25	14	14
ELMO1	0.008	0.036	-10000	0	-0.41	4	4
RhoG/GTP/ELMO1/DOCK1	0.01	0.038	-10000	0	-0.26	10	10
NGF	-0.078	0.17	-10000	0	-0.41	114	114
HRAS	0.011	0	-10000	0	-10000	0	0
DOCK1	0.006	0.048	-10000	0	-0.41	7	7
GAB2	0.008	0.036	-10000	0	-0.41	4	4
RIT2	0.002	0.004	-10000	0	-10000	0	0
RIT1	0.011	0	-10000	0	-10000	0	0
FRS2	0.011	0	-10000	0	-10000	0	0
DNM1	0.006	0.044	-10000	0	-0.41	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.011	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.12	0.16	0.19	2	-0.31	183	185
mol:GDP	-0.063	0.11	-10000	0	-0.28	28	28
NGF (dimer)	-0.078	0.17	-10000	0	-0.41	114	114
RhoG/GDP	0.006	0.025	-10000	0	-0.29	4	4
RIT1/GDP	-0.04	0.08	-10000	0	-0.2	22	22
TIAM1	0	0.067	-10000	0	-0.41	14	14
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
BDNF (dimer)/TRKB	-0.039	0.1	-10000	0	-0.2	149	149
KIDINS220/CRKL/C3G	0.016	0	-10000	0	-10000	0	0
SHC/RasGAP	0.014	0.028	-10000	0	-0.28	5	5
FRS2 family/SHP2	0.022	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0.027	0.019	-10000	0	-0.2	4	4
RIT1/GTP	0.008	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.018	0.1	-10000	0	-0.4	37	37
RAP1/GDP	-0.048	0.053	-10000	0	-0.17	22	22
KIDINS220/CRKL	0.011	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.042	0.12	-10000	0	-0.33	84	84
ubiquitin-dependent protein catabolic process	-0.037	0.11	-10000	0	-0.23	120	120
Schwann cell development	-0.037	0.03	-10000	0	-10000	0	0
EHD4	0.011	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.028	0	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.031	0.017	-10000	0	-10000	0	0
RAP1B	0.011	0	-10000	0	-10000	0	0
RAP1A	0.011	0	-10000	0	-10000	0	0
CDC42/GTP	-0.12	0.12	-10000	0	-0.34	102	102
ABL1	0.009	0.026	-10000	0	-0.41	2	2
SH2B family/GRB2/SOS1	0.016	0	-10000	0	-10000	0	0
Rap1/GTP	0.015	0.046	-10000	0	-10000	0	0
STAT3	0.017	0.01	-10000	0	-10000	0	0
axon guidance	-0.12	0.12	-10000	0	-0.32	102	102
MAPK3	-0.032	0.1	-10000	0	-0.27	17	17
MAPK1	-0.032	0.1	-10000	0	-0.21	129	129
CDC42/GDP	-0.04	0.08	-10000	0	-0.2	19	19
NTF3	-0.018	0.1	-10000	0	-0.4	37	37
NTF4	-0.007	0.071	-10000	0	-0.33	24	24
NGF (dimer)/TRKA/FAIM	-0.037	0.11	-10000	0	-0.23	121	121
PI3K	0.013	0.031	-10000	0	-0.28	6	6
FRS3	0.011	0	-10000	0	-10000	0	0
FAIM	0.01	0.018	-10000	0	-0.41	1	1
GAB1	0.008	0.036	-10000	0	-0.41	4	4
RASGRF1	-0.15	0.17	0.2	2	-0.35	188	190
SOS1	0.011	0	-10000	0	-10000	0	0
MCF2L	-0.11	0.14	-10000	0	-0.25	265	265
RGS19	0.011	0	-10000	0	-10000	0	0
CDC42	0.011	0	-10000	0	-10000	0	0
RAS family/GTP	-0.017	0.07	-10000	0	-10000	0	0
Rac1/GDP	-0.04	0.08	-10000	0	-0.2	22	22
NGF (dimer)/TRKA/GRIT	-0.044	0.11	-10000	0	-0.24	125	125
neuron projection morphogenesis	-0.11	0.17	-10000	0	-0.43	68	68
NGF (dimer)/TRKA/NEDD4-2	-0.037	0.11	-10000	0	-0.23	120	120
MAP2K1	0.029	0.018	-10000	0	-10000	0	0
NGFR	-0.13	0.2	-10000	0	-0.41	182	182
NGF (dimer)/TRKA/GIPC/GAIP	-0.023	0.096	-10000	0	-0.2	124	124
RAS family/GTP/PI3K	0.023	0.023	-10000	0	-0.2	6	6
FRS2 family/SHP2/GRB2/SOS1	0.033	0	-10000	0	-10000	0	0
NRAS	0.011	0	-10000	0	-10000	0	0
GRB2/SOS1	0.016	0	-10000	0	-10000	0	0
PRKCI	0.011	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.011	0	-10000	0	-10000	0	0
PRKCZ	0.01	0.023	-10000	0	-0.37	2	2
MAPKKK cascade	-0.15	0.25	-10000	0	-0.6	121	121
RASA1	0.007	0.04	-10000	0	-0.41	5	5
TRKA/c-Abl	0.008	0.044	-10000	0	-0.25	15	15
SQSTM1	0.011	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.027	0.093	-10000	0	-0.21	61	61
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.018	0.091	-10000	0	-0.21	12	12
MATK	0	0.066	-10000	0	-0.4	14	14
NEDD4L	0.01	0.018	-10000	0	-0.41	1	1
RAS family/GDP	-0.044	0.05	-10000	0	-0.17	16	16
NGF (dimer)/TRKA	-0.14	0.17	0.21	2	-0.31	235	237
Rac1/GTP	-0.11	0.11	-10000	0	-0.26	168	168
FRS2 family/SHP2/CRK family	0.033	0	-10000	0	-10000	0	0

×

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

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
MAP4K1	-0.029	0.15	-10000	0	-0.41	51	51
CRKL	-0.033	0.15	-10000	0	-0.43	51	51
HRAS	-0.012	0.13	-10000	0	-0.38	45	45
mol:PIP3	-0.039	0.14	0.19	2	-0.4	53	55
SPRED1	0.011	0	-10000	0	-10000	0	0
SPRED2	0.01	0.018	-10000	0	-0.41	1	1
GAB1	-0.041	0.16	-10000	0	-0.37	81	81
FOXO3	-0.024	0.14	-10000	0	-0.39	48	48
AKT1	-0.033	0.15	-10000	0	-0.43	48	48
BAD	-0.024	0.14	-10000	0	-0.39	48	48
megakaryocyte differentiation	-0.042	0.16	-10000	0	-0.36	80	80
GSK3B	-0.024	0.14	-10000	0	-0.39	48	48
RAF1	-0.002	0.11	-10000	0	-0.3	45	45
SHC1	0.011	0	-10000	0	-10000	0	0
STAT3	-0.039	0.16	-10000	0	-0.37	79	79
STAT1	-0.099	0.34	-10000	0	-0.84	81	81
HRAS/SPRED1	-0.004	0.11	-10000	0	-0.3	45	45
cell proliferation	-0.04	0.16	-10000	0	-0.36	81	81
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
TEC	0.01	0.015	-10000	0	-0.33	1	1
RPS6KB1	-0.04	0.16	-10000	0	-0.37	79	79
HRAS/SPRED2	-0.004	0.11	-10000	0	-0.31	45	45
LYN/TEC/p62DOK	-0.026	0.15	-10000	0	-0.42	49	49
MAPK3	0.01	0.086	-10000	0	-0.23	30	30
STAP1	-0.042	0.16	-10000	0	-0.36	81	81
GRAP2	-0.002	0.074	-10000	0	-0.41	17	17
JAK2	-0.086	0.3	-10000	0	-0.72	81	81
STAT1 (dimer)	-0.096	0.33	-10000	0	-0.82	81	81
mol:Gleevec	0	0.006	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.028	0.15	-10000	0	-0.42	51	51
actin filament polymerization	-0.038	0.15	-10000	0	-0.36	81	81
LYN	0.011	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.052	0.21	-10000	0	-0.51	81	81
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
CBL/CRKL/GRB2	-0.019	0.14	-10000	0	-0.39	48	48
PI3K	-0.03	0.16	-10000	0	-0.45	50	50
PTEN	0.006	0.044	-10000	0	-0.41	6	6
SCF/KIT/EPO/EPOR	-0.099	0.37	-10000	0	-1.2	47	47
MAPK8	-0.041	0.16	-10000	0	-0.37	81	81
STAT3 (dimer)	-0.038	0.15	-10000	0	-0.36	79	79
positive regulation of transcription	0.012	0.073	-10000	0	-0.19	26	26
mol:GDP	-0.017	0.14	-10000	0	-0.39	46	46
PIK3C2B	-0.039	0.16	-10000	0	-0.37	79	79
CBL/CRKL	-0.025	0.14	-10000	0	-0.41	48	48
FER	-0.039	0.16	-10000	0	-0.37	79	79
SH2B3	-0.04	0.16	-10000	0	-0.36	81	81
PDPK1	-0.031	0.13	0.18	2	-0.38	50	52
SNAI2	-0.064	0.18	-10000	0	-0.41	91	91
positive regulation of cell proliferation	-0.069	0.26	-10000	0	-0.62	81	81
KITLG	-0.029	0.13	-10000	0	-0.43	50	50
cell motility	-0.069	0.26	-10000	0	-0.62	81	81
PTPN6	0.011	0.017	-10000	0	-0.33	1	1
EPOR	-0.01	0.12	-10000	0	-0.46	14	14
STAT5A (dimer)	-0.055	0.21	-10000	0	-0.52	81	81
SOCS1	0.01	0.018	-10000	0	-0.41	1	1
cell migration	0.043	0.16	0.36	80	-10000	0	80
SOS1	0.011	0	-10000	0	-10000	0	0
EPO	-0.005	0.074	-10000	0	-0.41	17	17
VAV1	0.007	0.037	-10000	0	-0.34	6	6
GRB10	-0.04	0.16	-10000	0	-0.36	82	82
PTPN11	0.012	0.006	-10000	0	-10000	0	0
SCF/KIT	-0.047	0.16	-10000	0	-0.34	107	107
GO:0007205	0.001	0.008	-10000	0	-10000	0	0
MAP2K1	0.007	0.093	-10000	0	-0.24	45	45
CBL	0.011	0	-10000	0	-10000	0	0
KIT	-0.078	0.34	-10000	0	-1.2	40	40
MAP2K2	0.007	0.093	-10000	0	-0.24	45	45
SHC/Grb2/SOS1	-0.026	0.15	-10000	0	-0.43	48	48
STAT5A	-0.058	0.22	-10000	0	-0.53	81	81
GRB2	0.011	0	-10000	0	-10000	0	0
response to radiation	-0.063	0.18	-10000	0	-0.4	92	92
SHC/GRAP2	0.007	0.052	-10000	0	-0.28	17	17
PTPRO	-0.043	0.16	-10000	0	-0.37	80	80
SH2B2	-0.039	0.16	-10000	0	-0.36	81	81
DOK1	0.011	0	-10000	0	-10000	0	0
MATK	-0.044	0.16	-10000	0	-0.37	80	80
CREBBP	0.016	0.045	-10000	0	-0.42	2	2
BCL2	-0.099	0.38	-10000	0	-1.2	51	51

×

TCGA08_retinoblastoma

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
CDKN2B	0.001	0.049	-10000	0	-0.35	9	9
CDKN2C	0.021	0.056	-10000	0	-0.38	9	9
CDKN2A	-0.14	0.17	-10000	0	-0.34	225	225
CCND2	0.005	0.049	0.16	10	-0.1	43	53
RB1	-0.006	0.048	0.13	5	-0.16	12	17
CDK4	0.024	0.037	0.17	12	-10000	0	12
CDK6	0.016	0.045	0.17	12	-0.18	11	23
G1/S progression	0.006	0.048	0.16	12	-0.13	5	17

×

Thromboxane A2 receptor signaling

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
TGM2	-0.032	0.13	-10000	0	-0.41	54	54
GNB1/GNG2	-0.04	0.072	-10000	0	-0.19	94	94
AKT1	-0.016	0.097	-10000	0	-0.2	94	94
EGF	-0.005	0.07	-10000	0	-0.34	23	23
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.017	0.054	-10000	0	-0.3	1	1
mol:Ca2+	-0.045	0.14	-10000	0	-0.3	116	116
LYN	0.021	0.047	-10000	0	-10000	0	0
RhoA/GTP	-0.028	0.049	-10000	0	-0.13	95	95
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.044	0.16	-10000	0	-0.34	107	107
GNG2	0.003	0.056	-10000	0	-0.4	10	10
ARRB2	0.011	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.004	0.071	-10000	0	-0.33	15	15
G beta5/gamma2	-0.053	0.097	-10000	0	-0.25	94	94
PRKCH	-0.052	0.16	-10000	0	-0.35	107	107
DNM1	0.006	0.044	-10000	0	-0.41	6	6
TXA2/TP beta/beta Arrestin3	-0.004	0.021	-10000	0	-0.21	1	1
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	-0.026	0.12	-10000	0	-0.41	47	47
G12 family/GTP	-0.069	0.12	-10000	0	-0.3	108	108
ADRBK1	0.011	0	-10000	0	-10000	0	0
ADRBK2	0.01	0.018	-10000	0	-0.41	1	1
RhoA/GTP/ROCK1	0.012	0.006	-10000	0	-10000	0	0
mol:GDP	0.021	0.093	0.22	49	-10000	0	49
mol:NADP	0.009	0.023	-10000	0	-0.37	2	2
RAB11A	0.011	0	-10000	0	-10000	0	0
PRKG1	-0.18	0.21	-10000	0	-0.41	238	238
mol:IP3	-0.061	0.18	-10000	0	-0.38	116	116
cell morphogenesis	0.012	0.006	-10000	0	-10000	0	0
PLCB2	-0.089	0.23	-10000	0	-0.51	116	116
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	0.007	0.056	-10000	0	-0.25	2	2
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.019	0.05	-10000	0	-0.26	1	1
RHOA	0.011	0	-10000	0	-10000	0	0
PTGIR	0.01	0.018	-10000	0	-0.41	1	1
PRKCB1	-0.057	0.17	-10000	0	-0.37	109	109
GNAQ	0.009	0.026	-10000	0	-0.41	2	2
mol:L-citrulline	0.009	0.023	-10000	0	-0.37	2	2
TXA2/TXA2-R family	-0.083	0.23	-10000	0	-0.52	107	107
LCK	0.02	0.049	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.014	0.045	-10000	0	-10000	0	0
TXA2-R family/G12 family/GDP/G beta/gamma	0.018	0.028	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.014	0.044	-10000	0	-10000	0	0
MAPK14	-0.022	0.11	-10000	0	-0.23	97	97
TGM2/GTP	-0.078	0.21	-10000	0	-0.45	119	119
MAPK11	-0.022	0.11	-10000	0	-0.23	98	98
ARHGEF1	-0.017	0.085	-10000	0	-0.18	101	101
GNAI2	0.011	0	-10000	0	-10000	0	0
JNK cascade	-0.056	0.17	-10000	0	-0.38	108	108
RAB11/GDP	0.011	0.001	-10000	0	-10000	0	0
ICAM1	-0.034	0.13	-10000	0	-0.28	96	96
cAMP biosynthetic process	-0.062	0.17	-10000	0	-0.36	119	119
Gq family/GTP/EBP50	-0.002	0.069	-10000	0	-0.18	65	65
actin cytoskeleton reorganization	0.012	0.006	-10000	0	-10000	0	0
SRC	0.021	0.047	-10000	0	-10000	0	0
GNB5	0.011	0	-10000	0	-10000	0	0
GNB1	0.011	0	-10000	0	-10000	0	0
EGF/EGFR	0.031	0.047	-10000	0	-0.21	3	3
VCAM1	-0.043	0.15	-10000	0	-0.33	96	96
TP beta/Gq family/GDP/G beta5/gamma2	0.004	0.071	-10000	0	-0.33	15	15
platelet activation	-0.031	0.14	-10000	0	-0.3	107	107
PGI2/IP	0.008	0.013	-10000	0	-0.29	1	1
PRKACA	-0.003	0.063	-10000	0	-0.21	48	48
Gq family/GDP/G beta5/gamma2	0.002	0.071	-10000	0	-0.31	15	15
TXA2/TP beta/beta Arrestin2	-0.006	0.047	-10000	0	-0.44	6	6
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.003	0.06	-10000	0	-0.19	48	48
mol:DAG	-0.067	0.19	-10000	0	-0.42	107	107
EGFR	0	0.066	-10000	0	-0.4	14	14
TXA2/TP alpha	-0.088	0.23	-10000	0	-0.49	119	119
Gq family/GTP	-0.024	0.071	-10000	0	-0.2	65	65
YES1	0.021	0.047	-10000	0	-10000	0	0
GNAI2/GTP	-0.013	0.041	-10000	0	-10000	0	0
PGD2/DP	-0.018	0.083	-10000	0	-0.29	47	47
SLC9A3R1	0.008	0.029	-10000	0	-0.33	4	4
FYN	0.021	0.047	-10000	0	-10000	0	0
mol:NO	0.009	0.023	-10000	0	-0.37	2	2
GNA15	0.007	0.039	-10000	0	-0.33	7	7
PGK/cGMP	-0.096	0.12	-10000	0	-0.24	239	239
RhoA/GDP	0.011	0.001	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.002	0.09	-10000	0	-0.34	17	17
NOS3	0.009	0.023	-10000	0	-0.37	2	2
RAC1	0.011	0	-10000	0	-10000	0	0
PRKCA	-0.059	0.17	-10000	0	-0.37	107	107
PRKCB	-0.058	0.17	-10000	0	-0.37	106	106
PRKCE	-0.049	0.16	-10000	0	-0.35	102	102
PRKCD	-0.055	0.17	-10000	0	-0.38	101	101
PRKCG	-0.065	0.18	-10000	0	-0.4	108	108
muscle contraction	-0.076	0.22	-10000	0	-0.48	108	108
PRKCZ	-0.045	0.16	-10000	0	-0.34	107	107
ARR3	0.003	0.015	-10000	0	-0.33	1	1
TXA2/TP beta	0.01	0.055	-10000	0	-10000	0	0
PRKCQ	-0.062	0.17	-10000	0	-0.37	109	109
MAPKKK cascade	-0.076	0.21	-10000	0	-0.46	109	109
SELE	-0.048	0.16	-10000	0	-0.36	96	96
TP beta/GNAI2/GDP/G beta/gamma	0.017	0.06	-10000	0	-0.33	2	2
ROCK1	0.011	0	-10000	0	-10000	0	0
GNA14	-0.032	0.13	-10000	0	-0.41	55	55
chemotaxis	-0.091	0.26	-10000	0	-0.6	96	96
GNA12	0.011	0	-10000	0	-10000	0	0
GNA13	0.011	0	-10000	0	-10000	0	0
GNA11	0.002	0.062	-10000	0	-0.41	12	12
Rac1/GTP	0.006	0.004	-10000	0	-10000	0	0

×

BMP 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.029	0.11	-9999	-0.22	117	117
SMAD6-7/SMURF1	0.021	0.019	-9999	-0.23	3	3
NOG	-0.019	0.096	-9999	-0.33	46	46
SMAD9	-0.058	0.17	-9999	-0.5	59	59
SMAD4	0.01	0.018	-9999	-0.41	1	1
SMAD5	-0.018	0.095	-9999	-0.3	30	30
BMP7/USAG1	-0.048	0.12	-9999	-0.26	123	123
SMAD5/SKI	-0.011	0.091	-9999	-0.29	28	28
SMAD1	0.034	0.014	-9999	-10000	0	0
BMP2	-0.025	0.12	-9999	-0.41	46	46
SMAD1/SMAD1/SMAD4	-0.001	0.012	-9999	-10000	0	0
BMPR1A	0.011	0	-9999	-10000	0	0
BMPR1B	-0.015	0.1	-9999	-0.41	34	34
BMPR1A-1B/BAMBI	-0.003	0.08	-9999	-0.24	54	54
AHSG	0	0.048	-9999	-0.33	11	11
CER1	0.004	0.005	-9999	-10000	0	0
BMP2-4/CER1	-0.018	0.092	-9999	-0.24	74	74
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.036	0.12	-9999	-0.34	39	39
BMP2-4 (homodimer)	-0.026	0.11	-9999	-0.29	74	74
RGMB	0.01	0.018	-9999	-0.41	1	1
BMP6/BMPR2/BMPR1A-1B	0.01	0.064	-9999	-0.2	43	43
RGMA	-0.08	0.17	-9999	-0.41	116	116
SMURF1	0.011	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.041	0.12	-9999	-0.34	41	41
BMP2-4/USAG1	-0.043	0.12	-9999	-0.24	135	135
SMAD6/SMURF1/SMAD5	-0.011	0.091	-9999	-0.28	30	30
SOSTDC1	-0.04	0.13	-9999	-0.36	72	72
BMP7/BMPR2/BMPR1A-1B	-0.008	0.088	-9999	-0.22	59	59
SKI	0.011	0	-9999	-10000	0	0
BMP6 (homodimer)	0.002	0.059	-9999	-0.41	11	11
HFE2	0.003	0.021	-9999	-0.33	2	2
ZFYVE16	0.011	0	-9999	-10000	0	0
MAP3K7	0.011	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.056	0.14	-9999	-0.26	148	148
SMAD5/SMAD5/SMAD4	-0.011	0.092	-9999	-0.29	30	30
MAPK1	0.011	0	-9999	-10000	0	0
TAK1/TAB family	-0.051	0.087	-9999	-0.3	37	37
BMP7 (homodimer)	-0.032	0.12	-9999	-0.37	61	61
NUP214	0.011	0	-9999	-10000	0	0
BMP6/FETUA	0.003	0.053	-9999	-0.25	22	22
SMAD1/SKI	0.038	0.014	-9999	-10000	0	0
SMAD6	0.01	0.018	-9999	-0.41	1	1
CTDSP2	0.011	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.02	0.097	-9999	-0.24	83	83
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.092	0.18	-9999	-0.41	132	132
BMPR2 (homodimer)	0.011	0	-9999	-10000	0	0
GADD34/PP1CA	0.022	0	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.002	0.072	-9999	-0.28	34	34
CHRDL1	-0.28	0.19	-9999	-0.41	368	368
ENDOFIN/SMAD1	0.038	0.014	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	0	0.012	-9999	-10000	0	0
SMAD6/SMURF1	0.011	0	-9999	-10000	0	0
BAMBI	-0.007	0.082	-9999	-0.38	24	24
SMURF2	0.011	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.18	0.15	-9999	-0.26	386	386
BMP2-4/GREM1	-0.073	0.14	-9999	-0.26	182	182
SMAD7	0.009	0.026	-9999	-0.41	2	2
SMAD8A/SMAD8A/SMAD4	-0.049	0.16	-9999	-0.47	59	59
SMAD1/SMAD6	0.038	0.014	-9999	-10000	0	0
TAK1/SMAD6	0.016	0	-9999	-10000	0	0
BMP7	-0.032	0.12	-9999	-0.37	61	61
BMP6	0.002	0.06	-9999	-0.41	11	11
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.037	0.11	-9999	-0.32	43	43
PPM1A	0.011	0	-9999	-10000	0	0
SMAD1/SMURF2	0.038	0.014	-9999	-10000	0	0
SMAD7/SMURF1	0.015	0.018	-9999	-0.28	2	2
CTDSPL	0.011	0	-9999	-10000	0	0
PPP1CA	0.011	0	-9999	-10000	0	0
XIAP	0.011	0	-9999	-10000	0	0
CTDSP1	0.011	0	-9999	-10000	0	0
PPP1R15A	0.011	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.076	0.16	-9999	-0.41	71	71
CHRD	-0.062	0.16	-9999	-0.41	94	94
BMPR2	0.011	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.05	0.13	-9999	-0.37	41	41
BMP4	-0.014	0.097	-9999	-0.39	34	34
FST	-0.043	0.14	-9999	-0.4	70	70
BMP2-4/NOG	-0.03	0.11	-9999	-0.23	113	113
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.002	0.082	-9999	-0.2	59	59

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.002	0.072	-10000	0	-0.19	70	70
ER alpha/Gai/GDP/Gbeta gamma	-0.087	0.19	-10000	0	-0.31	183	183
AKT1	-0.07	0.25	-10000	0	-0.74	62	62
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.074	0.25	-10000	0	-0.76	62	62
mol:Ca2+	-0.016	0.12	-10000	0	-0.34	58	58
IGF1R	-0.005	0.081	-10000	0	-0.41	21	21
E2/ER alpha (dimer)/Striatin	-0.014	0.08	-10000	0	-0.23	63	63
SHC1	0.011	0	-10000	0	-10000	0	0
apoptosis	0.066	0.24	0.71	62	-10000	0	62
RhoA/GTP	-0.018	0.05	-10000	0	-0.3	1	1
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.087	0.14	-10000	0	-0.39	73	73
regulation of stress fiber formation	-0.017	0.058	0.26	3	-10000	0	3
E2/ERA-ERB (dimer)	-0.014	0.079	-10000	0	-0.23	62	62
KRAS	0.01	0.015	-10000	0	-0.33	1	1
G13/GTP	-0.011	0.071	-10000	0	-0.21	61	61
pseudopodium formation	0.017	0.058	-10000	0	-0.26	3	3
E2/ER alpha (dimer)/PELP1	-0.013	0.079	-10000	0	-0.23	61	61
GRB2	0.011	0	-10000	0	-10000	0	0
GNG2	0.003	0.056	-10000	0	-0.4	10	10
GNAO1	-0.1	0.18	-10000	0	-0.41	142	142
HRAS	0.011	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.056	0.18	-10000	0	-0.49	63	63
E2/ER beta (dimer)	0.008	0.01	-10000	0	-0.23	1	1
mol:GDP	-0.035	0.098	-10000	0	-0.31	61	61
mol:NADP	-0.056	0.18	-10000	0	-0.49	63	63
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
mol:IP3	-0.017	0.13	-10000	0	-0.35	58	58
IGF-1R heterotetramer	-0.005	0.081	-10000	0	-0.41	21	21
PLCB1	-0.023	0.13	-10000	0	-0.37	58	58
PLCB2	-0.022	0.13	-10000	0	-0.37	57	57
IGF1	-0.068	0.16	-10000	0	-0.41	101	101
mol:L-citrulline	-0.056	0.18	-10000	0	-0.49	63	63
RHOA	0.011	0	-10000	0	-10000	0	0
Gai/GDP	-0.15	0.29	-10000	0	-0.63	143	143
JNK cascade	0.008	0.01	-10000	0	-0.22	1	1
BCAR1	0.011	0	-10000	0	-10000	0	0
ESR2	0.01	0.015	-10000	0	-0.33	1	1
GNAQ	0.009	0.026	-10000	0	-0.41	2	2
ESR1	-0.037	0.13	-10000	0	-0.41	61	61
Gq family/GDP/Gbeta gamma	-0.003	0.094	-10000	0	-0.39	16	16
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.009	0.082	-10000	0	-0.26	21	21
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.087	0.14	-10000	0	-0.39	73	73
GNAZ	-0.001	0.069	-10000	0	-0.41	15	15
E2/ER alpha (dimer)	-0.025	0.094	-10000	0	-0.29	61	61
STRN	0.009	0.026	-10000	0	-0.41	2	2
GNAL	-0.051	0.15	-10000	0	-0.41	79	79
PELP1	0.011	0	-10000	0	-10000	0	0
MAPK11	0.014	0.017	-10000	0	-0.22	3	3
GNAI2	0.011	0	-10000	0	-10000	0	0
GNAI3	0.011	0	-10000	0	-10000	0	0
GNAI1	0.005	0.051	-10000	0	-0.41	8	8
HBEGF	-0.1	0.18	-10000	0	-0.36	119	119
cAMP biosynthetic process	-0.047	0.089	-10000	0	-0.2	128	128
SRC	-0.077	0.18	-10000	0	-0.29	183	183
PI3K	0.013	0.031	-10000	0	-0.28	6	6
GNB1	0.011	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.032	0.085	-10000	0	-0.26	61	61
SOS1	0.011	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.099	0.15	-10000	0	-0.36	110	110
Gs family/GTP	-0.048	0.091	-10000	0	-0.2	128	128
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.021	0.008	-10000	0	-10000	0	0
vasodilation	-0.053	0.17	-10000	0	-0.47	63	63
mol:DAG	-0.017	0.13	-10000	0	-0.35	58	58
Gs family/GDP/Gbeta gamma	-0.051	0.1	-10000	0	-0.29	65	65
MSN	0.017	0.062	-10000	0	-0.28	3	3
Gq family/GTP	-0.029	0.13	-10000	0	-0.39	57	57
mol:PI-3-4-5-P3	-0.071	0.24	-10000	0	-0.73	62	62
NRAS	0.011	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.053	0.17	0.47	63	-10000	0	63
GRB2/SOS1	0.016	0	-10000	0	-10000	0	0
RhoA/GDP	-0.033	0.091	-10000	0	-0.29	61	61
NOS3	-0.059	0.19	-10000	0	-0.52	63	63
GNA11	0.002	0.062	-10000	0	-0.41	12	12
MAPKKK cascade	-0.05	0.19	-10000	0	-0.54	63	63
E2/ER alpha (dimer)/PELP1/Src	-0.092	0.15	-10000	0	-0.41	73	73
ruffle organization	0.017	0.058	-10000	0	-0.26	3	3
ROCK2	0.012	0.065	-10000	0	-0.31	3	3
GNA14	-0.032	0.13	-10000	0	-0.41	55	55
GNA15	0.007	0.039	-10000	0	-0.33	7	7
GNA13	0.011	0	-10000	0	-10000	0	0
MMP9	-0.13	0.18	-10000	0	-0.4	117	117
MMP2	-0.076	0.18	-10000	0	-0.4	80	80

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.028	0.1	0.28	76	-10000	0	76
KIRREL	-0.039	0.14	-10000	0	-0.41	63	63
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.028	0.1	-10000	0	-0.28	76	76
PLCG1	0.011	0	-10000	0	-10000	0	0
ARRB2	0.011	0	-10000	0	-10000	0	0
WASL	0.011	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.01	0.075	-10000	0	-0.2	64	64
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.004	0.077	-10000	0	-0.21	63	63
FYN	-0.013	0.071	-10000	0	-0.2	64	64
mol:Ca2+	-0.014	0.074	-10000	0	-0.2	64	64
mol:DAG	-0.011	0.075	-10000	0	-0.2	64	64
NPHS2	-0.004	0.028	-10000	0	-0.33	3	3
mol:IP3	-0.011	0.075	-10000	0	-0.2	64	64
regulation of endocytosis	-0.005	0.067	-10000	0	-0.18	64	64
Nephrin/NEPH1/podocin/Cholesterol	-0.017	0.075	-10000	0	-0.2	78	78
establishment of cell polarity	-0.028	0.1	-10000	0	-0.28	76	76
Nephrin/NEPH1/podocin/NCK1-2	-0.003	0.072	-10000	0	-0.2	32	32
Nephrin/NEPH1/beta Arrestin2	-0.005	0.068	-10000	0	-0.18	64	64
NPHS1	-0.005	0.055	-10000	0	-0.33	14	14
Nephrin/NEPH1/podocin	-0.013	0.072	-10000	0	-0.2	64	64
TJP1	0.01	0.018	-10000	0	-0.41	1	1
NCK1	0.009	0.026	-10000	0	-0.41	2	2
NCK2	0.011	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.01	0.075	-10000	0	-0.2	64	64
CD2AP	0.011	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.01	0.075	-10000	0	-0.2	64	64
GRB2	0.011	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.026	0.096	-10000	0	-0.22	93	93
cytoskeleton organization	-0.001	0.08	-10000	0	-0.21	63	63
Nephrin/NEPH1	-0.017	0.07	-10000	0	-0.19	76	76
Nephrin/NEPH1/ZO-1	-0.013	0.082	-10000	0	-0.22	64	64

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.01	0.018	-9999	-0.41	1	1
CCL5	0.003	0.054	-9999	-0.37	11	11
SDCBP	0.011	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.071	0.069	-9999	-0.26	28	28
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.061	0.066	-9999	-0.24	29	29
Syndecan-1/Syntenin	-0.061	0.066	-9999	-0.25	28	28
MAPK3	-0.045	0.062	-9999	-0.25	15	15
HGF/MET	-0.048	0.12	-9999	-0.28	115	115
TGFB1/TGF beta receptor Type II	0.01	0.018	-9999	-0.41	1	1
BSG	0.011	0	-9999	-10000	0	0
keratinocyte migration	-0.061	0.065	-9999	-0.24	29	29
Syndecan-1/RANTES	-0.064	0.073	-9999	-0.26	36	36
Syndecan-1/CD147	-0.053	0.064	-9999	-0.24	28	28
Syndecan-1/Syntenin/PIP2	-0.059	0.063	-9999	-0.24	28	28
LAMA5	0.01	0.015	-9999	-0.33	1	1
positive regulation of cell-cell adhesion	-0.058	0.062	-9999	-0.23	28	28
MMP7	-0.057	0.14	-9999	-0.36	98	98
HGF	-0.075	0.17	-9999	-0.41	110	110
Syndecan-1/CASK	-0.067	0.065	-9999	-0.25	28	28
Syndecan-1/HGF/MET	-0.095	0.11	-9999	-0.27	123	123
regulation of cell adhesion	-0.038	0.06	-9999	-0.24	15	15
HPSE	0.003	0.058	-9999	-0.4	11	11
positive regulation of cell migration	-0.071	0.069	-9999	-0.26	28	28
SDC1	-0.071	0.07	-9999	-0.27	28	28
Syndecan-1/Collagen	-0.071	0.069	-9999	-0.26	28	28
PPIB	0.01	0.015	-9999	-0.33	1	1
MET	0.005	0.046	-9999	-0.37	8	8
PRKACA	0.011	0	-9999	-10000	0	0
MMP9	-0.13	0.17	-9999	-0.33	220	220
MAPK1	-0.045	0.062	-9999	-0.25	15	15
homophilic cell adhesion	-0.07	0.069	-9999	-0.26	28	28
MMP1	-0.17	0.17	-9999	-0.33	292	292

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	0.005	0.067	-9999	-0.25	30	30
alphaM/beta2 Integrin/GPIbA	0.014	0.041	-9999	-0.23	11	11
alphaM/beta2 Integrin/proMMP-9	-0.062	0.1	-9999	-0.18	223	223
PLAUR	0.01	0.021	-9999	-0.33	2	2
HMGB1	0.009	0.011	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	0.017	0.033	-9999	-0.21	9	9
AGER	0.008	0.021	-9999	-0.4	1	1
RAP1A	0.011	0	-9999	-10000	0	0
SELPLG	0.01	0.021	-9999	-0.33	2	2
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	0.018	0.057	-9999	-0.27	3	3
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.13	0.17	-9999	-0.33	220	220
CYR61	-0.027	0.12	-9999	-0.41	48	48
TLN1	0.011	0	-9999	-10000	0	0
Rap1/GTP	-0.028	0.061	-9999	-0.26	15	15
RHOA	0.011	0	-9999	-10000	0	0
P-selectin oligomer	-0.15	0.2	-9999	-0.41	204	204
MYH2	-0.03	0.11	-9999	-0.31	35	35
MST1R	-0.021	0.1	-9999	-0.33	51	51
leukocyte activation during inflammatory response	-0.015	0.05	-9999	-0.21	17	17
APOB	0	0.052	-9999	-0.39	9	9
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.01	0.092	-9999	-0.41	27	27
JAM3	-0.1	0.19	-9999	-0.41	144	144
GP1BA	0.008	0.03	-9999	-0.38	3	3
alphaM/beta2 Integrin/CTGF	0.011	0.053	-9999	-0.24	19	19
alphaM/beta2 Integrin	-0.022	0.085	-9999	-0.23	39	39
JAM3 homodimer	-0.1	0.19	-9999	-0.41	144	144
ICAM2	0.011	0	-9999	-10000	0	0
ICAM1	0.008	0.029	-9999	-0.33	4	4
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.022	0.084	-9999	-0.23	39	39
cell adhesion	0.014	0.041	-9999	-0.23	11	11
NFKB1	0.018	0.086	-9999	-0.28	26	26
THY1	0.011	0	-9999	-10000	0	0
RhoA/GDP	0.008	0	-9999	-10000	0	0
Lipoprotein(a)	-0.006	0.055	-9999	-0.2	40	40
alphaM/beta2 Integrin/LRP/tPA	-0.002	0.081	-9999	-0.21	63	63
IL6	0.012	0.13	-9999	-0.53	23	23
ITGB2	0.006	0.034	-9999	-0.33	5	5
elevation of cytosolic calcium ion concentration	0.021	0.035	-9999	-0.19	9	9
alphaM/beta2 Integrin/JAM2/JAM3	-0.11	0.17	-9999	-0.28	243	243
JAM2	-0.14	0.2	-9999	-0.41	189	189
alphaM/beta2 Integrin/ICAM1	0.01	0.063	-9999	-0.36	3	3
alphaM/beta2 Integrin/uPA/Plg	-0.001	0.076	-9999	-0.21	53	53
RhoA/GTP	-0.033	0.11	-9999	-0.26	70	70
positive regulation of phagocytosis	-0.02	0.055	-9999	-0.24	11	11
Ron/MSP	-0.009	0.073	-9999	-0.22	58	58
alphaM/beta2 Integrin/uPAR/uPA	0.022	0.035	-9999	-0.19	9	9
alphaM/beta2 Integrin/uPAR	0.017	0.036	-9999	-0.2	11	11
PLAU	0.009	0.025	-9999	-0.33	3	3
PLAT	-0.035	0.13	-9999	-0.41	59	59
actin filament polymerization	-0.029	0.1	-9999	-0.3	35	35
MST1	0.007	0.039	-9999	-0.33	7	7
alphaM/beta2 Integrin/lipoprotein(a)	0.005	0.057	-9999	-0.21	17	17
TNF	0.011	0.11	-9999	-0.39	10	10
RAP1B	0.011	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	0.016	0.037	-9999	-0.21	12	12
fibrinolysis	-0.001	0.075	-9999	-0.21	53	53
HCK	0.007	0.039	-9999	-0.33	7	7
dendritic cell antigen processing and presentation	-0.022	0.084	-9999	-0.23	39	39
VTN	-0.046	0.14	-9999	-0.41	72	72
alphaM/beta2 Integrin/CYR61	-0.005	0.08	-9999	-0.23	55	55
LPA	-0.012	0.08	-9999	-0.33	32	32
LRP1	0.009	0.026	-9999	-0.41	2	2
cell migration	-0.06	0.1	-9999	-0.25	41	41
FN1	0.007	0.04	-9999	-0.41	5	5
alphaM/beta2 Integrin/Thy1	0.017	0.033	-9999	-0.24	5	5
MPO	0.005	0.041	-9999	-0.33	8	8
KNG1	-0.01	0.069	-9999	-0.33	24	24
RAP1/GDP	0.015	0	-9999	-10000	0	0
ROCK1	-0.026	0.11	-9999	-0.31	34	34
ELA2	0	0	-9999	-10000	0	0
PLG	-0.033	0.12	-9999	-0.4	55	55
CTGF	0	0.067	-9999	-0.41	14	14
alphaM/beta2 Integrin/Hck	0.015	0.044	-9999	-0.22	14	14
ITGAM	0.006	0.038	-9999	-0.37	5	5
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.062	0.12	-9999	-0.2	208	208
HP	-0.1	0.17	-9999	-0.35	166	166
leukocyte adhesion	-0.11	0.13	-9999	-0.32	118	118
SELP	-0.15	0.2	-9999	-0.41	204	204

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.014	0.076	-9999	-0.24	53	53
EFNA5	-0.004	0.076	-9999	-0.4	19	19
FYN	-0.006	0.069	-9999	-0.21	53	53
neuron projection morphogenesis	-0.014	0.076	-9999	-0.24	53	53
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.014	0.076	-9999	-0.24	53	53
EPHA5	-0.023	0.1	-9999	-0.41	36	36

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.1	0.25	-10000	0	-0.68	36	36
PCK1	-0.12	0.32	-10000	0	-1.2	35	35
HNF4A	-0.16	0.33	-10000	0	-0.84	69	69
KCNJ11	-0.089	0.26	-10000	0	-0.7	33	33
AKT1	-0.049	0.14	-10000	0	-0.37	11	11
response to starvation	-0.01	0.032	-10000	0	-10000	0	0
DLK1	-0.15	0.34	-10000	0	-0.82	73	73
NKX2-1	-0.02	0.15	-10000	0	-0.5	1	1
ACADM	-0.1	0.26	-10000	0	-0.71	37	37
TAT	-0.098	0.2	-10000	0	-0.59	27	27
CEBPB	0.013	0.002	-10000	0	-10000	0	0
CEBPA	0.01	0.038	-10000	0	-0.38	5	5
TTR	-0.038	0.13	-10000	0	-0.6	8	8
PKLR	-0.11	0.25	-10000	0	-0.68	40	40
APOA1	-0.21	0.44	-10000	0	-1.2	70	70
CPT1C	-0.1	0.26	-10000	0	-0.74	38	38
ALAS1	-0.044	0.16	-10000	0	-10000	0	0
TFRC	-0.058	0.19	-10000	0	-0.64	7	7
FOXF1	0.008	0.046	-10000	0	-0.4	6	6
NF1	0.015	0.026	-10000	0	-0.4	2	2
HNF1A (dimer)	0.004	0.047	-10000	0	-0.35	8	8
CPT1A	-0.1	0.25	-10000	0	-0.68	37	37
HMGCS1	-0.1	0.25	-10000	0	-0.68	35	35
NR3C1	-0.067	0.16	-10000	0	-0.39	94	94
CPT1B	-0.1	0.25	-10000	0	-0.68	36	36
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.007	0.016	-10000	0	-10000	0	0
GCK	-0.17	0.34	-10000	0	-0.79	95	95
CREB1	0.004	0.041	-10000	0	-0.19	9	9
IGFBP1	-0.22	0.44	-10000	0	-1.2	88	88
PDX1	-0.053	0.15	-10000	0	-0.47	7	7
UCP2	-0.1	0.25	-10000	0	-0.68	37	37
ALDOB	-0.091	0.26	-10000	0	-0.7	33	33
AFP	-0.056	0.072	-10000	0	-0.4	10	10
BDH1	-0.1	0.25	-10000	0	-0.68	36	36
HADH	-0.088	0.26	-10000	0	-0.71	30	30
F2	-0.15	0.31	-10000	0	-0.85	44	44
HNF1A	0.004	0.047	-10000	0	-0.35	8	8
G6PC	0.007	0.066	-10000	0	-10000	0	0
SLC2A2	-0.057	0.17	-10000	0	-0.48	3	3
INS	0.016	0.06	0.21	21	-10000	0	21
FOXA1	-0.21	0.16	-10000	0	-0.32	359	359
FOXA3	-0.057	0.15	-10000	0	-0.33	117	117
FOXA2	-0.11	0.3	-10000	0	-0.75	42	42
ABCC8	-0.18	0.38	-10000	0	-0.85	105	105
ALB	-0.063	0.14	-10000	0	-0.85	12	12

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.002	0.071	-9999	-0.28	32	32
PDGFRB	-0.007	0.084	-9999	-0.42	22	22
SPHK1	-0.013	0.023	-9999	-10000	0	0
mol:S1P	-0.016	0.03	-9999	-10000	0	0
S1P1/S1P/Gi	-0.079	0.19	-9999	-0.31	181	181
GNAO1	-0.1	0.19	-9999	-0.41	142	142
PDGFB-D/PDGFRB/PLCgamma1	-0.064	0.17	-9999	-0.38	91	91
PLCG1	-0.068	0.18	-9999	-0.4	87	87
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.007	0.084	-9999	-0.41	22	22
GNAI2	0.011	0.004	-9999	-10000	0	0
GNAI3	0.01	0.004	-9999	-10000	0	0
GNAI1	0.004	0.052	-9999	-0.42	8	8
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.001	0.06	-9999	-0.24	32	32
S1P1/S1P	-0.023	0.064	-9999	-0.27	15	15
negative regulation of cAMP metabolic process	-0.076	0.18	-9999	-0.3	181	181
MAPK3	-0.088	0.22	-9999	-0.53	86	86
calcium-dependent phospholipase C activity	-0.001	0.003	-9999	-10000	0	0
Rac1/GDP	0.008	0	-9999	-10000	0	0
RhoA/GDP	0.008	0	-9999	-10000	0	0
KDR	-0.014	0.1	-9999	-0.41	32	32
PLCB2	0.004	0.068	-9999	-0.24	15	15
RAC1	0.011	0	-9999	-10000	0	0
RhoA/GTP	-0.019	0.055	-9999	-0.23	15	15
receptor internalization	-0.022	0.061	-9999	-0.25	15	15
PTGS2	-0.12	0.33	-9999	-0.89	72	72
Rac1/GTP	-0.019	0.055	-9999	-0.23	15	15
RHOA	0.011	0	-9999	-10000	0	0
VEGFA	0.011	0.002	-9999	-10000	0	0
negative regulation of T cell proliferation	-0.076	0.18	-9999	-0.3	181	181
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.002	0.07	-9999	-0.42	15	15
MAPK1	-0.088	0.22	-9999	-0.53	86	86
S1P1/S1P/PDGFB-D/PDGFRB	-0.004	0.098	-9999	-0.3	30	30
ABCC1	0.01	0.002	-9999	-10000	0	0

×

Ras signaling in the CD4+ TCR 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.077	0.17	-9999	-0.31	167	167
MAP3K8	0.006	0.032	-9999	-0.41	3	3
FOS	-0.045	0.12	-9999	-0.38	26	26
PRKCA	-0.02	0.1	-9999	-0.41	36	36
PTPN7	0.005	0.038	-9999	-0.34	6	6
HRAS	0.01	0.001	-9999	-10000	0	0
PRKCB	-0.017	0.1	-9999	-0.41	32	32
NRAS	0.01	0.001	-9999	-10000	0	0
RAS family/GTP	0.015	0.013	-9999	-10000	0	0
MAPK3	-0.017	0.069	-9999	-0.25	5	5
MAP2K1	-0.039	0.15	-9999	-0.4	64	64
ELK1	0.005	0.01	-9999	-10000	0	0
BRAF	-0.035	0.14	-9999	-0.38	64	64
mol:GTP	-0.001	0.002	-9999	-0.005	165	165
MAPK1	-0.017	0.069	-9999	-0.21	25	25
RAF1	-0.035	0.14	-9999	-0.38	64	64
KRAS	0.01	0.015	-9999	-0.33	1	1

×

Osteopontin-mediated 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.039	0.1	-9999	-0.32	16	16
NF kappa B1 p50/RelA/I kappa B alpha	-0.013	0.092	-9999	-0.27	15	15
alphaV/beta3 Integrin/Osteopontin/Src	-0.043	0.1	-9999	-0.21	153	153
AP1	-0.081	0.15	-9999	-0.37	66	66
ILK	-0.051	0.11	-9999	-0.33	18	18
bone resorption	-0.028	0.1	-9999	-0.3	30	30
PTK2B	0.011	0	-9999	-10000	0	0
PYK2/p130Cas	-0.034	0.098	-9999	-0.3	17	17
ITGAV	0.014	0.001	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.005	0.057	-9999	-0.28	21	21
alphaV/beta3 Integrin/Osteopontin	-0.065	0.12	-9999	-0.24	107	107
MAP3K1	-0.051	0.11	-9999	-0.29	25	25
JUN	0.006	0.048	-9999	-0.41	7	7
MAPK3	-0.037	0.1	-9999	-0.32	16	16
MAPK1	-0.037	0.1	-9999	-0.32	16	16
Rac1/GDP	0.008	0	-9999	-10000	0	0
NFKB1	0.01	0.018	-9999	-0.41	1	1
MAPK8	-0.043	0.1	-9999	-0.32	23	23
ITGB3	-0.063	0.16	-9999	-0.4	100	100
NFKBIA	-0.025	0.099	-9999	-0.3	16	16
FOS	-0.12	0.19	-9999	-0.41	165	165
CD44	0.006	0.048	-9999	-0.41	7	7
CHUK	0.011	0	-9999	-10000	0	0
PLAU	-0.021	0.095	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.046	0.06	-9999	-0.26	15	15
BCAR1	0.011	0	-9999	-10000	0	0
RELA	0.011	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.032	0.11	-9999	-0.27	100	100
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.052	0.11	-9999	-0.32	21	21
VAV3	-0.08	0.12	-9999	-0.3	68	68
MAP3K14	-0.049	0.11	-9999	-0.32	20	20
ROCK2	0	0.067	-9999	-0.41	14	14
SPP1	-0.082	0.15	-9999	-0.32	153	153
RAC1	0.011	0	-9999	-10000	0	0
Rac1/GTP	-0.068	0.11	-9999	-0.27	68	68
MMP2	-0.073	0.15	-9999	-0.48	36	36

×

Ephrin B reverse signaling

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
EFNB2	0.009	0.031	-10000	0	-0.41	3	3
EPHB2	0.01	0.025	-10000	0	-0.33	3	3
EFNB1	0.015	0.037	-10000	0	-0.32	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.009	0.071	-10000	0	-0.35	4	4
Ephrin B2/EPHB1-2	-0.001	0.068	-10000	0	-0.2	54	54
neuron projection morphogenesis	-0.021	0.056	-10000	0	-0.33	4	4
Ephrin B1/EPHB1-2/Tiam1	0.006	0.076	-10000	0	-0.38	4	4
DNM1	0.007	0.044	-10000	0	-0.41	6	6
cell-cell signaling	0.001	0.002	-10000	0	-10000	0	0
MAP2K4	-0.048	0.18	-10000	0	-0.52	67	67
YES1	-0.093	0.25	-10000	0	-0.76	67	67
Ephrin B1/EPHB1-2/NCK2	0.011	0.067	-10000	0	-0.38	1	1
PI3K	-0.048	0.18	-10000	0	-0.53	68	68
mol:GDP	0.005	0.075	-10000	0	-0.37	4	4
ITGA2B	0.006	0.046	-10000	0	-0.4	7	7
endothelial cell proliferation	0.014	0.021	-10000	0	-0.23	4	4
FYN	-0.093	0.25	-10000	0	-0.76	67	67
MAP3K7	-0.056	0.19	-10000	0	-0.56	67	67
FGR	-0.095	0.25	-10000	0	-0.76	67	67
TIAM1	0	0.067	-10000	0	-0.41	14	14
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
RGS3	0.011	0	-10000	0	-10000	0	0
cell adhesion	-0.071	0.2	-10000	0	-0.56	67	67
LYN	-0.093	0.25	-10000	0	-0.76	67	67
Ephrin B1/EPHB1-2/Src Family Kinases	-0.087	0.23	-10000	0	-0.7	67	67
Ephrin B1/EPHB1-2	-0.075	0.2	-10000	0	-0.6	67	67
SRC	-0.092	0.25	-10000	0	-0.75	67	67
ITGB3	-0.067	0.16	-10000	0	-0.41	100	100
EPHB1	-0.03	0.12	-10000	0	-0.4	53	53
EPHB4	0.01	0.018	-10000	0	-0.41	1	1
RAC1	0.011	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.014	0.021	-10000	0	-0.23	4	4
alphaIIb/beta3 Integrin	-0.042	0.12	-10000	0	-0.28	107	107
BLK	-0.092	0.25	-10000	0	-0.75	67	67
HCK	-0.092	0.25	-10000	0	-0.75	67	67
regulation of stress fiber formation	-0.01	0.066	0.37	1	-10000	0	1
MAPK8	-0.042	0.17	-10000	0	-0.5	67	67
Ephrin B1/EPHB1-2/RGS3	0.011	0.067	-10000	0	-0.38	1	1
endothelial cell migration	-0.054	0.16	-10000	0	-0.46	67	67
NCK2	0.011	0	-10000	0	-10000	0	0
PTPN13	-0.057	0.18	-10000	0	-0.52	67	67
regulation of focal adhesion formation	-0.01	0.066	0.37	1	-10000	0	1
chemotaxis	-0.01	0.066	0.37	1	-10000	0	1
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
Rac1/GTP	-0.022	0.057	-10000	0	-0.34	4	4
angiogenesis	-0.075	0.2	-10000	0	-0.6	67	67
LCK	-0.092	0.25	-10000	0	-0.75	67	67

×

TCGA08_p53

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.089	0.12	-9999	-0.23	225	225
TP53	-0.023	0.03	-9999	-0.34	1	1
Senescence	-0.023	0.03	-9999	-0.34	1	1
Apoptosis	-0.023	0.03	-9999	-0.34	1	1
Activated_Oncogenes	0	0	-9999	-10000	0	0
MDM2	0.047	0.055	-9999	-10000	0	0
MDM4	0.011	0	-9999	-10000	0	0

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.006	0.074	-9999	-0.23	44	44
NF kappa B1 p50/RelA/I kappa B alpha	0.007	0.068	-9999	-0.26	4	4
AP1	-0.08	0.11	-9999	-0.36	48	48
mol:PIP3	-0.029	0.068	-9999	-0.32	15	15
AKT1	0.029	0.056	-9999	-0.27	8	8
PTK2B	0.006	0.059	-9999	-0.21	26	26
RHOA	0.019	0.03	-9999	-10000	0	0
PIK3CB	0.011	0	-9999	-10000	0	0
mol:Ca2+	0.005	0.063	-9999	-0.24	5	5
MAGI3	0.011	0	-9999	-10000	0	0
RELA	0.011	0	-9999	-10000	0	0
apoptosis	-0.01	0.084	-9999	-0.23	61	61
HRAS/GDP	0.008	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.01	0.065	-9999	-0.24	12	12
NF kappa B1 p50/RelA	-0.025	0.068	-9999	-0.33	10	10
endothelial cell migration	-0.01	0.12	-9999	-0.53	27	27
ADCY4	-0.043	0.14	-9999	-0.37	54	54
ADCY5	-0.07	0.16	-9999	-0.38	76	76
ADCY6	-0.035	0.13	-9999	-0.34	46	46
ADCY7	-0.035	0.13	-9999	-0.34	46	46
ADCY1	-0.044	0.14	-9999	-0.37	55	55
ADCY2	-0.14	0.19	-9999	-0.4	140	140
ADCY3	-0.036	0.13	-9999	-0.35	48	48
ADCY8	-0.038	0.13	-9999	-0.35	46	46
ADCY9	-0.063	0.16	-9999	-0.38	84	84
GSK3B	0.011	0.056	-9999	-0.22	14	14
arachidonic acid secretion	-0.04	0.13	-9999	-0.4	36	36
GNG2	0.003	0.056	-9999	-0.4	10	10
TRIP6	0.014	0.037	-9999	-0.35	5	5
GNAO1	-0.061	0.14	-9999	-0.26	162	162
HRAS	0.011	0	-9999	-10000	0	0
NFKBIA	0.01	0.076	-9999	-0.27	8	8
GAB1	0.008	0.036	-9999	-0.41	4	4
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.002	0.14	-9999	-0.86	14	14
JUN	0.005	0.048	-9999	-0.41	7	7
LPA/LPA2/NHERF2	0.012	0.023	-9999	-0.18	3	3
TIAM1	-0.025	0.16	-9999	-1	14	14
PIK3R1	0.007	0.04	-9999	-0.41	5	5
mol:IP3	0.005	0.064	-9999	-0.25	5	5
PLCB3	0.018	0.02	-9999	-10000	0	0
FOS	-0.12	0.19	-9999	-0.41	165	165
positive regulation of mitosis	-0.04	0.13	-9999	-0.4	36	36
LPA/LPA1-2-3	-0.012	0.088	-9999	-0.23	47	47
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.011	0	-9999	-10000	0	0
stress fiber formation	0.008	0.068	-9999	-0.31	8	8
GNAZ	-0.003	0.084	-9999	-0.25	51	51
EGFR/PI3K-beta/Gab1	-0.03	0.07	-9999	-0.33	15	15
positive regulation of dendritic cell cytokine production	-0.017	0.086	-9999	-0.24	42	42
LPA/LPA2/MAGI-3	0.012	0.023	-9999	-0.18	3	3
ARHGEF1	0.015	0.061	-9999	-0.37	5	5
GNAI2	0.003	0.072	-9999	-0.25	38	38
GNAI3	0.003	0.072	-9999	-0.25	38	38
GNAI1	0	0.078	-9999	-0.25	45	45
LPA/LPA3	-0.019	0.08	-9999	-0.26	50	50
LPA/LPA2	0.005	0.027	-9999	-0.22	3	3
LPA/LPA1	-0.007	0.084	-9999	-0.3	38	38
HB-EGF/EGFR	-0.064	0.1	-9999	-0.18	226	226
HBEGF	-0.078	0.12	-9999	-0.22	220	220
mol:DAG	0.005	0.064	-9999	-0.25	5	5
cAMP biosynthetic process	-0.066	0.15	-9999	-0.28	140	140
NFKB1	0.01	0.018	-9999	-0.41	1	1
SRC	0.011	0	-9999	-10000	0	0
GNB1	0.011	0	-9999	-10000	0	0
LYN	0.01	0.076	-9999	-0.27	8	8
GNAQ	-0.002	0.059	-9999	-0.22	28	28
LPAR2	0.009	0.025	-9999	-0.33	3	3
LPAR3	-0.025	0.11	-9999	-0.37	50	50
LPAR1	-0.006	0.084	-9999	-0.45	16	16
IL8	-0.071	0.11	-9999	-0.34	36	36
PTK2	-0.003	0.082	-9999	-0.38	8	8
Rac1/GDP	0.008	0	-9999	-10000	0	0
CASP3	-0.01	0.085	-9999	-0.23	61	61
EGFR	0	0.066	-9999	-0.4	14	14
PLCG1	-0.009	0.074	-9999	-0.22	45	45
PLD2	-0.004	0.083	-9999	-0.38	8	8
G12/G13	0.01	0.065	-9999	-0.22	38	38
PI3K-beta	-0.014	0.049	-9999	-0.29	9	9
cell migration	-0.013	0.049	-9999	-0.25	16	16
SLC9A3R2	0.011	0	-9999	-10000	0	0
PXN	0.008	0.068	-9999	-0.32	8	8
HRAS/GTP	-0.041	0.14	-9999	-0.41	36	36
RAC1	0.011	0	-9999	-10000	0	0
MMP9	-0.13	0.17	-9999	-0.33	220	220
PRKCE	0.011	0.001	-9999	-10000	0	0
PRKCD	0.01	0.061	-9999	-0.24	4	4
Gi(beta/gamma)	-0.034	0.12	-9999	-0.34	47	47
mol:LPA	-0.004	0.034	-9999	-0.16	22	22
TRIP6/p130 Cas/FAK1/Paxillin	-0.023	0.071	-9999	-0.39	9	9
MAPKKK cascade	-0.04	0.13	-9999	-0.4	36	36
contractile ring contraction involved in cytokinesis	0.019	0.03	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.025	0.095	-9999	-0.24	79	79
GNA15	-0.003	0.06	-9999	-0.22	26	26
GNA12	0.011	0	-9999	-10000	0	0
GNA13	0.011	0	-9999	-10000	0	0
MAPT	0.009	0.066	-9999	-0.26	11	11
GNA11	-0.006	0.066	-9999	-0.22	38	38
Rac1/GTP	-0.002	0.15	-9999	-0.91	14	14
MMP2	-0.01	0.13	-9999	-0.53	27	27

×

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

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
MET/RANBP9	0.012	0.032	-10000	0	-0.25	8	8
CRKL	-0.013	0.096	-10000	0	-0.41	10	10
mol:PIP3	-0.009	0.042	0.38	6	-10000	0	6
AKT1	0.005	0.03	0.28	6	-10000	0	6
PTK2B	0.011	0	-10000	0	-10000	0	0
RAPGEF1	-0.007	0.091	-10000	0	-0.38	10	10
RANBP10	0.011	0	-10000	0	-10000	0	0
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
HGF/MET/SHIP2	-0.032	0.1	-10000	0	-0.23	115	115
MAP3K5	0	0.089	-10000	0	-0.36	12	12
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.021	0.096	-10000	0	-0.2	111	111
AP1	-0.067	0.12	-10000	0	-0.25	166	166
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.011	0	-10000	0	-10000	0	0
apoptosis	-0.21	0.34	-10000	0	-0.71	166	166
STAT3 (dimer)	-0.016	0.097	-10000	0	-0.2	114	114
GAB1/CRKL/SHP2/PI3K	-0.034	0.076	-10000	0	-0.4	11	11
INPP5D	0.01	0.018	-10000	0	-0.41	1	1
CBL/CRK	-0.007	0.092	-10000	0	-0.38	10	10
PTPN11	0.011	0	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.011	0	-10000	0	-10000	0	0
PTEN	0.006	0.044	-10000	0	-0.41	6	6
ELK1	-0.003	0.018	-10000	0	-0.15	4	4
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.026	0.052	-10000	0	-0.22	8	8
PAK1	0.01	0.028	0.27	6	-10000	0	6
HGF/MET/RANBP10	-0.032	0.1	-10000	0	-0.23	115	115
HRAS	-0.025	0.12	-10000	0	-0.55	6	6
DOCK1	-0.01	0.097	-10000	0	-0.41	12	12
GAB1	-0.02	0.1	-10000	0	-0.2	113	113
CRK	-0.013	0.096	-10000	0	-0.41	10	10
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.087	0.17	-10000	0	-0.42	111	111
JUN	0.006	0.048	-10000	0	-0.41	7	7
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.025	0.075	-10000	0	-0.17	111	111
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
cell morphogenesis	0	0.11	-10000	0	-0.4	10	10
GRB2/SHC	-0.009	0.067	-10000	0	-0.29	4	4
FOS	-0.12	0.19	-10000	0	-0.41	165	165
GLMN	0	0	-10000	0	-10000	0	0
cell motility	-0.003	0.018	-10000	0	-0.15	4	4
HGF/MET/MUC20	-0.039	0.1	-10000	0	-0.24	115	115
cell migration	-0.009	0.066	-10000	0	-0.29	4	4
GRB2	0.011	0	-10000	0	-10000	0	0
CBL	0.011	0	-10000	0	-10000	0	0
MET/RANBP10	0.012	0.032	-10000	0	-0.25	8	8
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.019	0.096	-10000	0	-0.2	114	114
MET/MUC20	0.004	0.032	-10000	0	-0.26	8	8
RAP1B	-0.001	0.087	-10000	0	-0.38	9	9
RAP1A	-0.001	0.087	-10000	0	-0.38	9	9
HGF/MET/RANBP9	-0.032	0.1	-10000	0	-0.23	115	115
RAF1	-0.017	0.11	-10000	0	-0.51	6	6
STAT3	-0.016	0.098	-10000	0	-0.2	114	114
cell proliferation	-0.024	0.13	-10000	0	-0.28	111	111
RPS6KB1	-0.003	0.029	-10000	0	-0.14	3	3
MAPK3	-0.007	0.017	-10000	0	-10000	0	0
MAPK1	-0.007	0.017	-10000	0	-10000	0	0
RANBP9	0.011	0	-10000	0	-10000	0	0
MAPK8	0.01	0.096	-10000	0	-0.39	15	15
SRC	-0.012	0.09	-10000	0	-0.37	5	5
PI3K	-0.011	0.072	-10000	0	-0.3	9	9
MET/Glomulin	0.007	0.028	-10000	0	-0.22	8	8
SOS1	0.011	0	-10000	0	-10000	0	0
MAP2K1	-0.011	0.1	-10000	0	-0.57	4	4
MET	0.005	0.046	-10000	0	-0.37	8	8
MAP4K1	-0.005	0.092	-10000	0	-0.38	10	10
PTK2	0.011	0	-10000	0	-10000	0	0
MAP2K2	-0.011	0.1	-10000	0	-0.57	4	4
BAD	0.01	0.028	0.27	6	-10000	0	6
MAP2K4	0.006	0.084	-10000	0	-0.36	10	10
SHP2/GRB2/SOS1/GAB1	-0.033	0.075	-10000	0	-0.39	10	10
INPPL1	0.011	0	-10000	0	-10000	0	0
PXN	0.011	0	-10000	0	-10000	0	0
SH3KBP1	0.011	0	-10000	0	-10000	0	0
HGS	-0.017	0.069	-10000	0	-0.15	111	111
PLCgamma1/PKC	0.008	0	-10000	0	-10000	0	0
HGF	-0.075	0.17	-10000	0	-0.41	110	110
RASA1	0.007	0.04	-10000	0	-0.41	5	5
NCK1	0.009	0.026	-10000	0	-0.41	2	2
PTPRJ	0.011	0	-10000	0	-10000	0	0
NCK/PLCgamma1	-0.012	0.076	-10000	0	-0.16	112	112
PDPK1	-0.002	0.034	0.31	6	-10000	0	6
HGF/MET/SHIP	-0.032	0.11	-10000	0	-0.23	116	116

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	0.01	0.015	-9999	-0.33	1	1
GPC2	-0.014	0.088	-9999	-0.33	39	39
GPC2/Midkine	-0.001	0.061	-9999	-0.22	40	40
neuron projection morphogenesis	-0.001	0.061	-9999	-0.22	40	40

×

IL4-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
BCL2L1	-0.24	0.37	-10000	0	-1	54	54
STAT6 (cleaved dimer)	-0.27	0.34	-10000	0	-0.95	76	76
IGHG1	-0.085	0.14	-10000	0	-0.35	21	21
IGHG3	-0.23	0.36	-10000	0	-0.96	65	65
AKT1	-0.1	0.2	-10000	0	-0.71	10	10
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.064	0.16	-10000	0	-0.6	9	9
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.12	0.23	-10000	0	-0.64	36	36
THY1	-0.24	0.37	-10000	0	-1.1	48	48
MYB	-0.021	0.1	-10000	0	-0.33	51	51
HMGA1	-0.037	0.12	-10000	0	-0.33	75	75
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.14	0.23	-10000	0	-0.61	39	39
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.1	0.2	-10000	0	-0.78	8	8
SP1	0.017	0.002	-10000	0	-10000	0	0
INPP5D	0.01	0.018	-10000	0	-0.41	1	1
SOCS5	0.017	0.013	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.22	0.37	-10000	0	-1	60	60
SOCS1	-0.14	0.26	-10000	0	-0.7	42	42
SOCS3	-0.1	0.21	-10000	0	-0.94	6	6
FCER2	-0.18	0.3	-10000	0	-0.84	40	40
PARP14	0.012	0.002	-10000	0	-10000	0	0
CCL17	-0.24	0.37	-10000	0	-1.1	47	47
GRB2	0.011	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.08	0.16	-10000	0	-0.71	4	4
T cell proliferation	-0.24	0.38	-10000	0	-1.1	53	53
IL4R/JAK1	-0.24	0.38	-10000	0	-1.1	52	52
EGR2	-0.27	0.46	-10000	0	-1.3	58	58
JAK2	-0.009	0.06	-10000	0	-0.42	9	9
JAK3	0.012	0.03	-10000	0	-0.33	4	4
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
JAK1	0.007	0.027	-10000	0	-0.4	2	2
COL1A2	-0.078	0.18	-10000	0	-1.4	5	5
CCL26	-0.24	0.37	-10000	0	-1	56	56
IL4R	-0.25	0.4	-10000	0	-1.1	51	51
PTPN6	0.017	0.018	-10000	0	-0.31	1	1
IL13RA2	-0.24	0.38	-10000	0	-1	59	59
IL13RA1	-0.002	0.027	-10000	0	-10000	0	0
IRF4	-0.061	0.22	-10000	0	-1.1	18	18
ARG1	-0.054	0.11	-10000	0	-10000	0	0
CBL	-0.12	0.22	-10000	0	-0.58	36	36
GTF3A	0.018	0.001	-10000	0	-10000	0	0
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
IL13RA1/JAK2	-0.008	0.051	-10000	0	-0.28	9	9
IRF4/BCL6	-0.054	0.2	-10000	0	-1	18	18
CD40LG	0.007	0.064	-10000	0	-0.42	12	12
MAPK14	-0.12	0.22	-10000	0	-0.63	24	24
mitosis	-0.096	0.2	-10000	0	-0.67	10	10
STAT6	-0.27	0.42	-10000	0	-1.1	62	62
SPI1	0.011	0.025	-10000	0	-0.33	3	3
RPS6KB1	-0.088	0.19	-10000	0	-0.64	10	10
STAT6 (dimer)	-0.27	0.42	-10000	0	-1.1	62	62
STAT6 (dimer)/PARP14	-0.25	0.39	-10000	0	-1.1	61	61
mast cell activation	0.006	0.011	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.095	0.19	-10000	0	-0.7	8	8
FRAP1	-0.1	0.2	-10000	0	-0.71	10	10
LTA	-0.24	0.37	-10000	0	-1	56	56
FES	0.01	0.018	-10000	0	-0.41	1	1
T-helper 1 cell differentiation	0.26	0.41	1.1	63	-10000	0	63
CCL11	-0.25	0.39	-10000	0	-1.1	62	62
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.095	0.19	-10000	0	-0.73	7	7
IL2RG	0.009	0.048	-10000	0	-0.36	9	9
IL10	-0.24	0.37	-10000	0	-1	54	54
IRS1	-0.03	0.12	-10000	0	-0.41	53	53
IRS2	-0.043	0.14	-10000	0	-0.41	69	69
IL4	-0.058	0.1	-10000	0	-10000	0	0
IL5	-0.24	0.37	-10000	0	-1.1	49	49
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.21	0.32	-10000	0	-0.84	58	58
COL1A1	-0.075	0.16	-10000	0	-1.5	1	1
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.24	0.38	-10000	0	-1.1	45	45
IL2R gamma/JAK3	0.015	0.046	-10000	0	-0.3	10	10
TFF3	-0.3	0.43	-10000	0	-1.2	74	74
ALOX15	-0.25	0.38	-10000	0	-1.1	51	51
MYBL1	0.011	0	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.21	0.32	-10000	0	-0.84	60	60
SHC1	0.011	0	-10000	0	-10000	0	0
CEBPB	0.013	0.003	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.12	0.21	-10000	0	-0.64	22	22
mol:PI-3-4-5-P3	-0.1	0.2	-10000	0	-0.71	10	10
PI3K	-0.11	0.21	-10000	0	-0.77	10	10
DOK2	0.008	0.031	-10000	0	-0.35	4	4
ETS1	0.017	0.02	-10000	0	-0.38	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.072	0.16	-10000	0	-0.62	5	5
ITGB3	-0.36	0.56	-10000	0	-1.3	115	115
PIGR	-0.33	0.47	-10000	0	-1.2	84	84
IGHE	0.019	0.033	-10000	0	-10000	0	0
MAPKKK cascade	-0.071	0.16	-10000	0	-0.61	5	5
BCL6	0.01	0.018	-10000	0	-0.41	1	1
OPRM1	-0.24	0.37	-10000	0	-1.1	48	48
RETNLB	-0.24	0.37	-10000	0	-1.1	46	46
SELP	-0.52	0.66	-10000	0	-1.3	208	208
AICDA	-0.23	0.36	-10000	0	-1	55	55

×

FAS signaling pathway (CD95)

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.019	0.059	0.2	52	-10000	0	52
RFC1	0.019	0.059	0.2	52	-10000	0	52
PRKDC	0.019	0.059	0.2	52	-10000	0	52
RIPK1	0.011	0.002	-10000	0	-10000	0	0
CASP7	-0.002	0.016	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1	0.018	0.065	0.19	59	-0.21	5	64
MAP2K4	0.037	0.056	-10000	0	-0.24	12	12
mol:ceramide	0.028	0.045	-10000	0	-0.24	4	4
GSN	0.017	0.063	0.2	51	-0.22	5	56
FASLG/FAS/FADD/FAF1/Caspase 8	0.037	0.055	-10000	0	-0.25	2	2
FAS	0.007	0.04	-10000	0	-0.41	5	5
BID	0.001	0.017	0.27	2	-10000	0	2
MAP3K1	0.034	0.038	-10000	0	-10000	0	0
MAP3K7	0.011	0.002	-10000	0	-10000	0	0
RB1	0.018	0.06	0.2	51	-0.22	2	53
CFLAR	0.011	0.002	-10000	0	-10000	0	0
HGF/MET	-0.062	0.13	-10000	0	-0.25	164	164
ARHGDIB	0.019	0.059	0.2	52	-10000	0	52
FADD	0.011	0.003	-10000	0	-10000	0	0
actin filament polymerization	-0.017	0.063	0.22	5	-0.2	51	56
NFKB1	-0.009	0.044	-10000	0	-0.65	1	1
MAPK8	0.036	0.086	-10000	0	-0.41	16	16
DFFA	0.019	0.059	0.2	52	-10000	0	52
DNA fragmentation during apoptosis	0.019	0.059	0.2	52	-10000	0	52
FAS/FADD/MET	0.017	0.036	-10000	0	-0.21	13	13
CFLAR/RIP1	0.015	0.003	-10000	0	-10000	0	0
FAIM3	0.009	0.029	-10000	0	-0.38	3	3
FAF1	0.011	0.004	-10000	0	-10000	0	0
PARP1	0.019	0.059	0.2	52	-10000	0	52
DFFB	0.019	0.059	0.2	52	-10000	0	52
CHUK	-0.008	0.039	-10000	0	-0.6	1	1
FASLG	0.003	0.055	-10000	0	-0.36	12	12
FAS/FADD	0.014	0.029	-10000	0	-0.28	5	5
HGF	-0.075	0.17	-10000	0	-0.41	110	110
LMNA	0.018	0.054	0.18	52	-10000	0	52
CASP6	0.019	0.059	0.2	52	-10000	0	52
CASP10	0.01	0.026	-10000	0	-0.41	2	2
CASP3	0.022	0.068	0.23	52	-10000	0	52
PTPN13	-0.041	0.14	-10000	0	-0.41	67	67
CASP8	0.001	0.02	0.33	2	-10000	0	2
IL6	-0.006	0.2	-10000	0	-1.2	16	16
MET	0.005	0.046	-10000	0	-0.37	8	8
ICAD/CAD	0.018	0.055	0.18	52	-10000	0	52
FASLG/FAS/FADD/FAF1/Caspase 10	0.028	0.046	-10000	0	-0.24	4	4
activation of caspase activity by cytochrome c	0.001	0.016	0.27	2	-10000	0	2
PAK2	0.019	0.059	0.2	52	-10000	0	52
BCL2	-0.028	0.12	-10000	0	-0.41	50	50

×

EGFR-dependent Endothelin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.011	0	-9999	-10000	0	0
EGFR	0	0.066	-9999	-0.4	14	14
EGF/EGFR	-0.066	0.099	-9999	-0.2	171	171
EGF/EGFR dimer/SHC/GRB2/SOS1	0.02	0.048	-9999	-0.34	1	1
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.11	0.19	-9999	-0.41	160	160
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.005	0.07	-9999	-0.34	23	23
EGF/EGFR dimer/SHC	0.007	0.057	-9999	-0.2	36	36
mol:GDP	-0.01	0.04	-9999	-0.33	1	1
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.006	0.048	-9999	-0.41	7	7
GRB2/SOS1	0.016	0	-9999	-10000	0	0
HRAS/GTP	-0.009	0.036	-9999	-0.3	1	1
SHC1	0.011	0	-9999	-10000	0	0
HRAS/GDP	-0.01	0.037	-9999	-0.31	1	1
FRAP1	0.016	0.045	-9999	-0.32	1	1
EGF/EGFR dimer	-0.002	0.068	-9999	-0.25	36	36
SOS1	0.011	0	-9999	-10000	0	0
GRB2	0.011	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.075	0.14	-9999	-0.28	164	164

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.015	0	-9999	-10000	0	0
ARNO/beta Arrestin1-2	-0.02	0.068	-9999	-0.33	1	1
EGFR	0	0.066	-9999	-0.4	14	14
EPHA2	0.011	0	-9999	-10000	0	0
USP6	0.011	0	-9999	-10000	0	0
IQSEC1	0.01	0.018	-9999	-0.41	1	1
EGFR/EGFR/EGF/EGF	-0.002	0.068	-9999	-0.25	36	36
ARRB2	0.008	0.002	-9999	-10000	0	0
mol:GTP	0.015	0.011	-9999	-0.14	1	1
ARRB1	0.009	0.026	-9999	-0.41	2	2
FBXO8	0.011	0	-9999	-10000	0	0
TSHR	-0.007	0.072	-9999	-0.34	23	23
EGF	-0.005	0.07	-9999	-0.34	23	23
somatostatin receptor activity	0	0	-9999	-0.001	64	64
ARAP2	0.009	0.031	-9999	-0.41	3	3
mol:GDP	-0.046	0.091	-9999	-0.22	73	73
mol:PI-3-4-5-P3	0	0	-9999	-0.001	52	52
ITGA2B	0.006	0.046	-9999	-0.4	7	7
ARF6	0.011	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.027	0.017	-9999	-0.2	2	2
ADAP1	0.011	0	-9999	-10000	0	0
KIF13B	0.011	0	-9999	-10000	0	0
HGF/MET	-0.048	0.12	-9999	-0.28	115	115
PXN	0.011	0	-9999	-10000	0	0
ARF6/GTP	-0.041	0.095	-9999	-0.23	61	61
EGFR/EGFR/EGF/EGF/ARFGEP100	0.007	0.058	-9999	-0.2	37	37
ADRB2	-0.063	0.16	-9999	-0.41	94	94
receptor agonist activity	0	0	-9999	0	75	75
actin filament binding	0	0	-9999	0	65	65
SRC	0.011	0	-9999	-10000	0	0
ITGB3	-0.067	0.16	-9999	-0.41	100	100
GNAQ	0.009	0.026	-9999	-0.41	2	2
EFA6/PI-4-5-P2	0	0	-9999	-0.001	59	59
ARF6/GDP	0.017	0.048	-9999	-0.27	5	5
ARF6/GDP/GULP/ACAP1	-0.047	0.11	-9999	-0.3	61	61
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.016	0.09	-9999	-0.2	104	104
ACAP1	0.008	0.036	-9999	-0.36	5	5
ACAP2	0.01	0.018	-9999	-0.41	1	1
LHCGR/beta Arrestin2	0.001	0.004	-9999	-10000	0	0
EFNA1	0.01	0.021	-9999	-0.33	2	2
HGF	-0.075	0.17	-9999	-0.41	110	110
CYTH3	0.009	0	-9999	-10000	0	0
CYTH2	0.007	0.002	-9999	-10000	0	0
NCK1	0.009	0.026	-9999	-0.41	2	2
fibronectin binding	0	0	-9999	0	61	61
endosomal lumen acidification	0	0	-9999	0	46	46
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.036	0.13	-9999	-0.41	60	60
GNAQ/ARNO	0.012	0.013	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	0	1	1
PIP3-E	0	0	-9999	0	8	8
MET	0.005	0.046	-9999	-0.37	8	8
GNA14	-0.032	0.13	-9999	-0.41	55	55
GNA15	0.006	0.039	-9999	-0.33	7	7
GIT1	0.011	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	60	60
GNA11	0.002	0.062	-9999	-0.41	12	12
LHCGR	0.001	0.003	-9999	-10000	0	0
AGTR1	-0.087	0.17	-9999	-0.41	121	121
desensitization of G-protein coupled receptor protein signaling pathway	0.001	0.004	-9999	-10000	0	0
IPCEF1/ARNO	0.006	0.043	-9999	-0.31	1	1
alphaIIb/beta3 Integrin	-0.042	0.12	-9999	-0.28	107	107

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.011	0	-9999	-10000	0	0
GNAT1/GTP	0.002	0.024	-9999	-0.23	6	6
Metarhodopsin II/Arrestin	0.006	0.015	-9999	-0.18	3	3
PDE6G/GNAT1/GTP	-0.008	0.059	-9999	-0.19	52	52
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.002	0.036	-9999	-0.33	6	6
GRK1	0.002	0.015	-9999	-0.33	1	1
CNG Channel	-0.03	0.064	-9999	-0.28	14	14
mol:Na +	-0.018	0.053	-9999	-0.34	6	6
mol:ADP	0.002	0.015	-9999	-0.33	1	1
RGS9-1/Gbeta5/R9AP	-0.041	0.11	-9999	-0.22	138	138
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.019	0.054	-9999	-0.34	6	6
CNGB1	-0.007	0.074	-9999	-0.33	27	27
RDH5	0.009	0.025	-9999	-0.33	3	3
SAG	0.005	0.005	-9999	-10000	0	0
mol:Ca2+	0.011	0.06	-9999	-0.32	6	6
Na + (4 Units)	-0.017	0.049	-9999	-0.31	6	6
RGS9	-0.081	0.17	-9999	-0.41	117	117
GNB1/GNGT1	-0.067	0.11	-9999	-0.22	190	190
GNAT1/GDP	-0.032	0.093	-9999	-0.2	118	118
GUCY2D	0.001	0.05	-9999	-0.33	12	12
GNGT1	-0.11	0.16	-9999	-0.33	190	190
GUCY2F	0.005	0.005	-9999	-10000	0	0
GNB5	0.011	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.003	0.066	-9999	-0.21	23	23
mol:11-cis-retinal	0.009	0.025	-9999	-0.33	3	3
mol:cGMP	0.007	0.046	-9999	-0.25	4	4
GNB1	0.011	0	-9999	-10000	0	0
Rhodopsin	0.009	0.025	-9999	-0.22	6	6
SLC24A1	0.011	0	-9999	-10000	0	0
CNGA1	0.002	0.054	-9999	-0.33	14	14
Metarhodopsin II	0.004	0.015	-9999	-0.16	4	4
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	0.005	0.049	-9999	-0.23	10	10
RGS9BP	-0.005	0.07	-9999	-0.33	24	24
Metarhodopsin II/Transducin	-0.014	0.038	-9999	-10000	0	0
GCAP Family/Ca ++	0.003	0.04	-9999	-0.18	25	25
PDE6A/B	0.002	0.063	-9999	-0.26	28	28
mol:Pi	-0.041	0.11	-9999	-0.22	138	138
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.046	0.087	-9999	-0.16	191	191
PDE6B	-0.007	0.085	-9999	-0.4	24	24
PDE6A	0.008	0.029	-9999	-0.33	4	4
PDE6G	-0.019	0.097	-9999	-0.33	47	47
RHO	0.003	0.026	-9999	-0.33	3	3
PDE6	-0.061	0.089	-9999	-0.33	21	21
GUCA1A	-0.003	0.059	-9999	-0.33	17	17
GC2/GCAP Family	0.006	0.04	-9999	-0.21	8	8
GUCA1C	0	0	-9999	-10000	0	0
GUCA1B	0.005	0.051	-9999	-0.41	8	8

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.011	0	-9999	-10000	0	0
VLDLR	0.009	0.026	-9999	-0.41	2	2
LRPAP1	0.011	0	-9999	-10000	0	0
NUDC	0.011	0	-9999	-10000	0	0
RELN/LRP8	-0.071	0.12	-9999	-0.23	200	200
CaM/Ca2+	0.008	0	-9999	-10000	0	0
KATNA1	0.011	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.058	0.11	-9999	-0.2	194	194
IQGAP1/CaM	0.016	0	-9999	-10000	0	0
DAB1	-0.001	0.052	-9999	-0.33	13	13
IQGAP1	0.011	0	-9999	-10000	0	0
PLA2G7	0.006	0.043	-9999	-0.4	6	6
CALM1	0.011	0	-9999	-10000	0	0
DYNLT1	0.011	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	0.014	0.022	-9999	-0.22	5	5
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.011	0	-9999	-10000	0	0
CDK5R1	0.01	0.015	-9999	-0.33	1	1
LIS1/Poliovirus Protein 3A	0.013	0	-9999	-10000	0	0
CDK5R2	-0.028	0.1	-9999	-0.33	57	57
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.077	0.12	-9999	-0.23	211	211
YWHAE	0.011	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.033	0.091	-9999	-0.22	18	18
MAP1B	-0.013	0.055	-9999	-0.25	27	27
RAC1	0.018	0	-9999	-10000	0	0
p35/CDK5	-0.04	0.097	-9999	-0.3	3	3
RELN	-0.14	0.2	-9999	-0.41	198	198
PAFAH/LIS1	0.019	0.025	-9999	-0.22	6	6
LIS1/CLIP170	0.022	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.039	0.054	-9999	-0.21	2	2
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.05	0.1	-9999	-0.24	8	8
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.041	0.095	-9999	-0.24	18	18
LIS1/IQGAP1	0.022	0	-9999	-10000	0	0
RHOA	0.018	0	-9999	-10000	0	0
PAFAH1B1	0.018	0	-9999	-10000	0	0
PAFAH1B3	0.005	0.044	-9999	-0.33	9	9
PAFAH1B2	0.01	0.018	-9999	-0.41	1	1
MAP1B/LIS1/Dynein heavy chain	0.012	0.037	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.027	0.088	-9999	-0.26	2	2
LRP8	0.008	0.033	-9999	-0.33	5	5
NDEL1/Katanin 60	-0.033	0.091	-9999	-0.22	18	18
P39/CDK5	-0.058	0.1	-9999	-0.31	19	19
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.022	0	-9999	-10000	0	0
CDK5	-0.048	0.1	-9999	-0.18	194	194
PPP2R5D	0.011	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.019	0	-9999	-10000	0	0
CSNK2A1	0.011	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.052	0.1	-9999	-0.19	80	80
RELN/VLDLR	-0.057	0.11	-9999	-0.2	193	193
CDC42	0.018	0	-9999	-10000	0	0

×

Syndecan-4-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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.014	0.043	-9999	-0.41	5	5
Syndecan-4/Syndesmos	-0.012	0.07	-9999	-10000	0	0
positive regulation of JNK cascade	-0.12	0.11	-9999	-0.35	37	37
Syndecan-4/ADAM12	-0.016	0.072	-9999	-10000	0	0
CCL5	0.003	0.054	-9999	-0.37	11	11
Rac1/GDP	0.008	0	-9999	-10000	0	0
DNM2	0.011	0	-9999	-10000	0	0
ITGA5	0.011	0	-9999	-10000	0	0
SDCBP	0.011	0	-9999	-10000	0	0
PLG	-0.029	0.12	-9999	-0.38	55	55
ADAM12	0.003	0.05	-9999	-0.33	12	12
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.011	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.039	0.042	-9999	-0.12	6	6
Syndecan-4/Laminin alpha1	-0.063	0.096	-9999	-0.34	18	18
Syndecan-4/CXCL12/CXCR4	-0.12	0.11	-9999	-0.37	37	37
Syndecan-4/Laminin alpha3	-0.018	0.075	-9999	-10000	0	0
MDK	0.01	0.015	-9999	-0.33	1	1
Syndecan-4/FZD7	-0.042	0.099	-9999	-0.4	7	7
Syndecan-4/Midkine	-0.013	0.07	-9999	-10000	0	0
FZD7	-0.055	0.15	-9999	-0.41	85	85
Syndecan-4/FGFR1/FGF	-0.11	0.1	-9999	-0.36	33	33
THBS1	-0.045	0.14	-9999	-0.41	72	72
integrin-mediated signaling pathway	-0.016	0.074	-9999	-0.37	2	2
positive regulation of MAPKKK cascade	-0.12	0.11	-9999	-0.35	37	37
Syndecan-4/TACI	-0.019	0.076	-9999	-0.34	2	2
CXCR4	0.011	0	-9999	-10000	0	0
cell adhesion	0.013	0.051	-9999	-0.16	40	40
Syndecan-4/Dynamin	-0.012	0.07	-9999	-10000	0	0
Syndecan-4/TSP1	-0.038	0.095	-9999	-0.37	9	9
Syndecan-4/GIPC	-0.012	0.07	-9999	-10000	0	0
Syndecan-4/RANTES	-0.016	0.075	-9999	-0.36	2	2
ITGB1	0.011	0	-9999	-10000	0	0
LAMA1	-0.1	0.16	-9999	-0.33	182	182
LAMA3	-0.001	0.069	-9999	-0.41	15	15
RAC1	0.011	0	-9999	-10000	0	0
PRKCA	-0.007	0.1	-9999	-0.37	36	36
Syndecan-4/alpha-Actinin	-0.012	0.07	-9999	-10000	0	0
TFPI	-0.038	0.14	-9999	-0.41	63	63
F2	-0.024	0.095	-9999	-0.33	47	47
alpha5/beta1 Integrin	0.016	0	-9999	-10000	0	0
positive regulation of cell adhesion	-0.061	0.097	-9999	-0.32	22	22
ACTN1	0.011	0	-9999	-10000	0	0
TNC	0.002	0.061	-9999	-0.4	12	12
Syndecan-4/CXCL12	-0.13	0.12	-9999	-0.38	40	40
FGF6	0	0	-9999	-10000	0	0
RHOA	0.011	0	-9999	-10000	0	0
CXCL12	-0.26	0.2	-9999	-0.41	341	341
TNFRSF13B	-0.003	0.059	-9999	-0.33	17	17
FGF2	-0.22	0.21	-9999	-0.41	291	291
FGFR1	0.01	0.018	-9999	-0.41	1	1
Syndecan-4/PI-4-5-P2	-0.019	0.069	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
FN1	0.011	0.04	-9999	-0.39	5	5
cell migration	-0.017	0.019	-9999	-10000	0	0
PRKCD	0.015	0.008	-9999	-10000	0	0
vasculogenesis	-0.037	0.092	-9999	-0.36	9	9
SDC4	-0.019	0.072	-9999	-10000	0	0
Syndecan-4/Tenascin C	-0.016	0.076	-9999	-0.38	2	2
Syndecan-4/PI-4-5-P2/PKC alpha	-0.031	0.034	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.012	0.07	-9999	-10000	0	0
MMP9	-0.13	0.17	-9999	-0.33	220	220
Rac1/GTP	0.013	0.052	-9999	-0.16	40	40
cytoskeleton organization	-0.012	0.068	-9999	-10000	0	0
GIPC1	0.011	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.035	0.097	-9999	-0.37	12	12

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.004	0.056	-9999	-0.2	35	35
RGS9BP	-0.005	0.07	-9999	-0.33	24	24
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0.002	0.015	-9999	-0.33	1	1
mol:Na +	-0.005	0.055	-9999	-0.23	30	30
mol:ADP	0.007	0.015	-9999	-0.22	2	2
GNAT2	0.007	0.026	-9999	-0.33	3	3
RGS9-1/Gbeta5/R9AP	-0.041	0.11	-9999	-0.22	138	138
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0.007	0.015	-9999	-0.19	3	3
GRK7	0.006	0.015	-9999	-0.33	1	1
CNGB3	-0.015	0.089	-9999	-0.41	26	26
Cone Metarhodopsin II/X-Arrestin	0.002	0.011	-9999	-0.23	1	1
mol:Ca2+	-0.002	0.05	-9999	-0.2	31	31
Cone PDE6	-0.031	0.092	-9999	-0.19	117	117
Cone Metarhodopsin II	0.006	0.011	-9999	-0.16	2	2
Na + (4 Units)	-0.002	0.05	-9999	-0.2	31	31
GNAT2/GDP	-0.03	0.093	-9999	-0.19	117	117
GNB5	0.011	0	-9999	-10000	0	0
mol:GMP (4 units)	0.008	0.016	-9999	-0.16	4	4
Cone Transducin	0.004	0.06	-9999	-0.22	35	35
SLC24A2	0.004	0.015	-9999	-0.33	1	1
GNB3/GNGT2	-0.003	0.075	-9999	-0.29	35	35
GNB3	-0.015	0.1	-9999	-0.41	33	33
GNAT2/GTP	0.006	0.018	-9999	-0.23	3	3
CNGA3	0.004	0.029	-9999	-0.33	4	4
ARR3	0.003	0.015	-9999	-0.33	1	1
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.005	0.055	-9999	-0.23	30	30
mol:Pi	-0.041	0.11	-9999	-0.22	138	138
Cone CNG Channel	-0.011	0.042	-9999	-0.18	26	26
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	0.004	0.015	-9999	-0.33	1	1
RGS9	-0.081	0.17	-9999	-0.41	117	117
PDE6C	0.003	0.015	-9999	-0.33	1	1
GNGT2	0.009	0.031	-9999	-0.41	3	3
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.002	0.004	-9999	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.007	0.049	-10000	0	-1.1	1	1
VDR	0.003	0.052	-10000	0	-0.33	13	13
FAM120B	0.011	0	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.01	0.086	-10000	0	-0.26	21	21
RXRs/LXRs/DNA/Oxysterols	0.017	0.086	-10000	0	-0.45	2	2
MED1	0.011	0	-10000	0	-10000	0	0
mol:9cRA	0.003	0.007	-10000	0	-10000	0	0
RARs/THRs/DNA/Src-1	-0.026	0.11	-10000	0	-0.21	128	128
RXRs/NUR77	-0.011	0.1	-10000	0	-0.21	95	95
RXRs/PPAR	-0.007	0.091	-10000	0	-0.2	93	93
NCOR2	0.011	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.003	0.036	-10000	0	-0.23	13	13
RARs/VDR/DNA/Vit D3	0.018	0.039	-10000	0	-0.18	11	11
RARA	0.011	0	-10000	0	-10000	0	0
NCOA1	0.01	0.018	-10000	0	-0.41	1	1
VDR/VDR/DNA	0.003	0.052	-10000	0	-0.33	13	13
RARs/RARs/DNA/9cRA	0.018	0.03	-10000	0	-0.19	11	11
RARG	0.011	0	-10000	0	-10000	0	0
RPS6KB1	0.012	0.03	-10000	0	-0.4	1	1
RARs/THRs/DNA/SMRT	-0.026	0.1	-10000	0	-0.2	128	128
THRA	0.003	0.057	-10000	0	-0.41	10	10
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.003	0.036	-10000	0	-0.23	13	13
RXRs/PPAR/9cRA/PGJ2/DNA	0	0.084	0.28	1	-0.2	69	70
NR1H4	-0.009	0.062	-10000	0	-0.33	19	19
RXRs/LXRs/DNA	0.018	0.083	-10000	0	-0.23	20	20
NR1H2	0.014	0.006	-10000	0	-10000	0	0
NR1H3	0.014	0.015	-10000	0	-0.32	1	1
RXRs/VDR/DNA/Vit D3	0	0.082	-10000	0	-0.2	68	68
NR4A1	-0.016	0.1	-10000	0	-0.41	35	35
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.003	0.071	-10000	0	-0.19	53	53
RXRG	-0.045	0.14	-10000	0	-0.4	77	77
RXR alpha/CCPG	0.018	0.007	-10000	0	-10000	0	0
RXRA	0.014	0.006	-10000	0	-10000	0	0
RXRB	0.015	0.005	-10000	0	-10000	0	0
THRB	-0.079	0.17	-10000	0	-0.41	115	115
PPARG	-0.012	0.096	-10000	0	-0.41	30	30
PPARD	0.011	0	-10000	0	-10000	0	0
TNF	0.011	0.11	-10000	0	-0.99	2	2
mol:Oxysterols	0.003	0.006	-10000	0	-10000	0	0
cholesterol transport	0.017	0.086	-10000	0	-0.45	2	2
PPARA	0.011	0	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.002	0.06	-10000	0	-0.41	11	11
RXRs/NUR77/BCL2	-0.039	0.13	-10000	0	-0.25	125	125
SREBF1	0.023	0.08	-10000	0	-0.5	1	1
RXRs/RXRs/DNA/9cRA	0.001	0.084	0.27	1	-0.2	69	70
ABCA1	0.023	0.08	-10000	0	-0.5	1	1
RARs/THRs	-0.021	0.099	-10000	0	-0.41	7	7
RXRs/FXR	-0.007	0.091	-10000	0	-0.22	68	68
BCL2	-0.028	0.12	-10000	0	-0.41	50	50

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.009	0.031	-9999	-0.41	3	3
SVIL	-0.035	0.13	-9999	-0.41	59	59
ZNF318	0.01	0.005	-9999	-10000	0	0
JMJD2C	-0.003	0.031	-9999	-0.12	35	35
T-DHT/AR/Ubc9	-0.025	0.1	-9999	-0.24	90	90
CARM1	0.011	0	-9999	-10000	0	0
PRDX1	0.011	0	-9999	-10000	0	0
PELP1	0.011	0.001	-9999	-10000	0	0
CTNNB1	0.011	0.002	-9999	-10000	0	0
AKT1	0.011	0.001	-9999	-10000	0	0
PTK2B	0.011	0.002	-9999	-10000	0	0
MED1	0.011	0.001	-9999	-10000	0	0
MAK	-0.013	0.087	-9999	-0.33	37	37
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	0.007	0.041	-9999	-0.41	5	5
GSN	0.007	0.044	-9999	-0.41	6	6
NCOA2	-0.004	0.078	-9999	-0.41	19	19
NCOA6	0.011	0.002	-9999	-10000	0	0
DNA-PK	0.022	0.005	-9999	-10000	0	0
NCOA4	0.011	0	-9999	-10000	0	0
PIAS3	0.011	0.002	-9999	-10000	0	0
cell proliferation	-0.013	0.024	-9999	-10000	0	0
XRCC5	0.011	0.001	-9999	-10000	0	0
UBE3A	0.012	0.002	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.045	0.12	-9999	-0.25	128	128
FHL2	0.001	0.11	-9999	-0.98	5	5
RANBP9	0.011	0.002	-9999	-10000	0	0
JMJD1A	0.005	0.03	-9999	-0.13	23	23
CDK6	0.001	0.065	-9999	-0.41	13	13
TGFB1I1	-0.12	0.2	-9999	-0.41	175	175
T-DHT/AR/CyclinD1	-0.025	0.1	-9999	-0.24	92	92
XRCC6	0.011	0.001	-9999	-10000	0	0
T-DHT/AR	-0.02	0.12	-9999	-0.26	97	97
CTDSP1	0.011	0.001	-9999	-10000	0	0
CTDSP2	0.01	0.003	-9999	-10000	0	0
BRCA1	0.011	0.002	-9999	-10000	0	0
TCF4	-0.005	0.079	-9999	-0.41	20	20
CDKN2A	-0.13	0.17	-9999	-0.33	225	225
SRF	0.016	0.011	-9999	-10000	0	0
NKX3-1	-0.023	0.17	-9999	-0.94	16	16
KLK3	-0.006	0.043	-9999	-10000	0	0
TMF1	0.011	0.001	-9999	-10000	0	0
HNRNPA1	0.011	0.002	-9999	-10000	0	0
AOF2	0	0.002	-9999	-10000	0	0
APPL1	0.018	0.003	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.025	0.1	-9999	-0.24	90	90
AR	-0.06	0.16	-9999	-0.42	90	90
UBA3	0.011	0.001	-9999	-10000	0	0
PATZ1	0.011	0.002	-9999	-10000	0	0
PAWR	0.011	0.001	-9999	-10000	0	0
PRKDC	0.011	0.001	-9999	-10000	0	0
PA2G4	0.011	0.002	-9999	-10000	0	0
UBE2I	0.011	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.021	0.093	-9999	-0.22	90	90
RPS6KA3	0.011	0.018	-9999	-0.41	1	1
T-DHT/AR/ARA70	-0.024	0.1	-9999	-0.24	90	90
LATS2	0.009	0.026	-9999	-0.41	2	2
T-DHT/AR/PRX1	-0.021	0.093	-9999	-0.22	90	90
Cyclin D3/CDK11 p58	0.008	0	-9999	-10000	0	0
VAV3	-0.069	0.14	-9999	-0.33	127	127
KLK2	-0.065	0.19	-9999	-0.87	28	28
CASP8	0.011	0.001	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.022	0.11	-9999	-0.22	103	103
TMPRSS2	-0.018	0.14	-9999	-0.64	17	17
CCND1	0.009	0.025	-9999	-0.33	3	3
PIAS1	0.012	0.002	-9999	-10000	0	0
mol:T-DHT	-0.001	0.02	-9999	-0.066	36	36
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.012	0.004	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.031	0.11	-9999	-0.25	102	102
CMTM2	0.008	0.025	-9999	-0.33	3	3
SNURF	-0.024	0.11	-9999	-0.41	41	41
ZMIZ1	0.008	0.037	-9999	-0.42	3	3
CCND3	0.011	0	-9999	-10000	0	0
TGIF1	0.011	0.002	-9999	-10000	0	0
FKBP4	0.011	0.002	-9999	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.038	0.12	-9999	-0.28	100	100
AKT1	0.021	0.15	-9999	-0.51	34	34
PTK2B	-0.021	0.15	-9999	-0.55	32	32
VEGFR2 homodimer/Frs2	-0.006	0.14	-9999	-0.56	32	32
CAV1	-0.062	0.16	-9999	-0.41	94	94
CALM1	0.011	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.004	0.13	-9999	-0.52	32	32
endothelial cell proliferation	0.017	0.15	-9999	-0.45	41	41
mol:Ca2+	-0.001	0.15	-9999	-0.55	32	32
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.011	0.12	-9999	-0.48	32	32
RP11-342D11.1	-0.008	0.15	-9999	-0.55	32	32
CDH5	0.006	0.048	-9999	-0.41	7	7
VEGFA homodimer	0.029	0.01	-9999	-0.2	1	1
SHC1	0.011	0	-9999	-10000	0	0
SHC2	-0.049	0.15	-9999	-0.41	77	77
HRAS/GDP	-0.034	0.11	-9999	-0.47	32	32
SH2D2A	-0.002	0.066	-9999	-0.33	21	21
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.034	0.11	-9999	-0.46	32	32
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.002	0.14	-9999	-0.53	32	32
VEGFR1 homodimer	0.011	0	-9999	-10000	0	0
SHC/GRB2/SOS1	-0.038	0.13	-9999	-0.52	32	32
GRB10	-0.001	0.15	-9999	-0.55	32	32
PTPN11	0.011	0	-9999	-10000	0	0
GRB2	0.011	0	-9999	-10000	0	0
PAK1	0.011	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.013	0.13	-9999	-0.5	32	32
HRAS	0.011	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	-0.013	0.12	-9999	-0.38	32	32
HIF1A	0.011	0	-9999	-10000	0	0
FRS2	0.011	0	-9999	-10000	0	0
oxygen and reactive oxygen species metabolic process	0.01	0.12	-9999	-0.48	32	32
mol:GTP	0	0	-9999	-10000	0	0
FLT4	-0.005	0.081	-9999	-0.41	21	21
Nck/Pak	0.015	0.018	-9999	-0.28	2	2
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.004	0.13	-9999	-0.52	32	32
mol:GDP	-0.037	0.12	-9999	-0.5	32	32
mol:NADP	0.024	0.12	-9999	-0.4	32	32
eNOS/Hsp90	0.028	0.11	-9999	-0.38	32	32
PIK3R1	0.007	0.04	-9999	-0.41	5	5
mol:IP3	-0.001	0.15	-9999	-0.55	32	32
HIF1A/ARNT	0.016	0	-9999	-10000	0	0
SHB	0.011	0	-9999	-10000	0	0
VEGFA	0.013	0.001	-9999	-10000	0	0
VEGFC	0.004	0.054	-9999	-0.41	9	9
FAK1/Vinculin	-0.009	0.16	-9999	-0.6	32	32
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.011	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.027	0.16	-9999	-0.58	32	32
PTPN6	0.01	0.015	-9999	-0.33	1	1
EPAS1	-0.001	0.084	-9999	-0.32	32	32
mol:L-citrulline	0.024	0.12	-9999	-0.4	32	32
ITGAV	0.011	0	-9999	-10000	0	0
PIK3CA	0.01	0.018	-9999	-0.41	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.011	0.12	-9999	-0.48	32	32
VEGFR2 homodimer/VEGFA homodimer	-0.008	0.16	-9999	-0.6	32	32
VEGFR2/3 heterodimer	-0.015	0.15	-9999	-0.45	50	50
VEGFB	0.011	0	-9999	-10000	0	0
MAPK11	-0.003	0.16	-9999	-0.57	33	33
VEGFR2 homodimer	-0.011	0.16	-9999	-0.65	32	32
FLT1	0.011	0	-9999	-10000	0	0
NEDD4	-0.02	0.11	-9999	-0.41	42	42
MAPK3	-0.006	0.14	-9999	-0.47	40	40
MAPK1	-0.006	0.14	-9999	-0.47	40	40
VEGFA145/NRP2	0.004	0.062	-9999	-0.28	25	25
VEGFR1/2 heterodimer	-0.006	0.14	-9999	-0.56	32	32
KDR	-0.011	0.16	-9999	-0.65	32	32
VEGFA165/NRP1/VEGFR2 homodimer	-0.01	0.16	-9999	-0.56	34	34
SRC	0.011	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	-0.005	0.15	-9999	-0.48	40	40
PI3K	0.011	0.16	-9999	-0.57	34	34
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.004	0.13	-9999	-0.52	32	32
FES	-0.002	0.15	-9999	-0.56	33	33
GAB1	-0.039	0.14	-9999	-0.6	32	32
VEGFR2 homodimer/VEGFA homodimer/Src	0.004	0.13	-9999	-0.52	32	32
CTNNB1	0.011	0	-9999	-10000	0	0
SOS1	0.011	0	-9999	-10000	0	0
ARNT	0.011	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.013	0.13	-9999	-0.41	41	41
VEGFR2 homodimer/VEGFA homodimer/Yes	0.004	0.13	-9999	-0.52	32	32
PI3K/GAB1	0.022	0.15	-9999	-0.53	34	34
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.015	0.12	-9999	-0.47	32	32
PRKACA	0.011	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.01	0.15	-9999	-0.56	32	32
HSP90AA1	0.011	0	-9999	-10000	0	0
CDC42	-0.002	0.15	-9999	-0.56	32	32
actin cytoskeleton reorganization	-0.002	0.14	-9999	-0.53	32	32
PTK2	-0.017	0.17	-9999	-0.64	32	32
EDG1	-0.008	0.15	-9999	-0.55	32	32
mol:DAG	-0.001	0.15	-9999	-0.55	32	32
CaM/Ca2+	0.004	0.14	-9999	-0.51	32	32
MAP2K3	0.004	0.14	-9999	-0.53	32	32
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.001	0.15	-9999	-0.57	32	32
PLCG1	-0.002	0.15	-9999	-0.56	32	32
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.011	0.12	-9999	-0.48	32	32
IQGAP1	0.011	0	-9999	-10000	0	0
YES1	0.011	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.004	0.13	-9999	-0.52	32	32
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.004	0.13	-9999	-0.52	32	32
cell migration	0.013	0.15	-9999	-0.53	32	32
mol:PI-3-4-5-P3	0.013	0.15	-9999	-0.52	34	34
FYN	0.011	0	-9999	-10000	0	0
VEGFB/NRP1	-0.001	0.14	-9999	-0.52	32	32
mol:NO	0.024	0.12	-9999	-0.4	32	32
PXN	0.011	0	-9999	-10000	0	0
HRAS/GTP	-0.034	0.11	-9999	-0.47	32	32
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.001	0.15	-9999	-0.57	32	32
VHL	0.01	0.018	-9999	-0.41	1	1
ITGB3	-0.067	0.16	-9999	-0.41	100	100
NOS3	0.023	0.13	-9999	-0.45	32	32
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.028	0.15	-9999	-0.55	32	32
RAC1	0.011	0	-9999	-10000	0	0
PRKCA	-0.008	0.15	-9999	-0.51	38	38
PRKCB	-0.007	0.15	-9999	-0.52	35	35
VCL	0.011	0	-9999	-10000	0	0
VEGFA165/NRP1	-0.007	0.15	-9999	-0.55	32	32
VEGFR1/2 heterodimer/VEGFA homodimer	0.004	0.13	-9999	-0.52	32	32
VEGFA165/NRP2	0.004	0.062	-9999	-0.28	25	25
MAPKKK cascade	0.02	0.13	-9999	-0.47	32	32
NRP2	-0.009	0.089	-9999	-0.41	25	25
VEGFC homodimer	0.004	0.054	-9999	-0.41	9	9
NCK1	0.009	0.026	-9999	-0.41	2	2
ROCK1	0.011	0	-9999	-10000	0	0
FAK1/Paxillin	-0.009	0.16	-9999	-0.6	32	32
MAP3K13	-0.003	0.15	-9999	-0.56	32	32
PDPK1	0.02	0.14	-9999	-0.46	34	34

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.011	0	-9999	-10000	0	0
HDAC2	0.011	0.001	-9999	-10000	0	0
GNB1/GNG2	0.015	0.041	-9999	-0.22	15	15
forebrain development	-0.068	0.2	-9999	-0.44	104	104
GNAO1	-0.1	0.18	-9999	-0.41	142	142
SMO/beta Arrestin2	0.015	0.029	-9999	-0.28	5	5
SMO	0.007	0.04	-9999	-0.41	5	5
ARRB2	0.011	0.003	-9999	-10000	0	0
GLI3/SPOP	-0.029	0.11	-9999	-0.46	4	4
mol:GTP	0	0.001	-9999	-10000	0	0
GSK3B	0.011	0	-9999	-10000	0	0
GNAI2	0.011	0.002	-9999	-10000	0	0
SIN3/HDAC complex	0.028	0.002	-9999	-10000	0	0
GNAI1	0.005	0.051	-9999	-0.41	8	8
XPO1	0.012	0.004	-9999	-10000	0	0
GLI1/Su(fu)	-0.066	0.13	-9999	-0.44	34	34
SAP30	0.011	0.001	-9999	-10000	0	0
mol:GDP	0.007	0.04	-9999	-0.41	5	5
MIM/GLI2A	0.013	0.018	-9999	-10000	0	0
IFT88	0.011	0	-9999	-10000	0	0
GNAI3	0.011	0.002	-9999	-10000	0	0
GLI2	-0.013	0.078	-9999	-10000	0	0
GLI3	-0.037	0.12	-9999	-0.22	149	149
CSNK1D	0.011	0	-9999	-10000	0	0
CSNK1E	0.011	0	-9999	-10000	0	0
SAP18	0.011	0	-9999	-10000	0	0
embryonic digit morphogenesis	0.011	0	-9999	-10000	0	0
GNG2	0.003	0.056	-9999	-0.4	10	10
Gi family/GTP	-0.039	0.11	-9999	-0.21	157	157
SIN3B	0.011	0.001	-9999	-10000	0	0
SIN3A	0.011	0	-9999	-10000	0	0
GLI3/Su(fu)	-0.004	0.087	-9999	-0.39	3	3
GLI2/Su(fu)	0.004	0.07	-9999	-0.23	3	3
FOXA2	-0.1	0.3	-9999	-1.1	48	48
neural tube patterning	-0.068	0.2	-9999	-0.44	104	104
SPOP	0.011	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.025	0.016	-9999	-10000	0	0
GNB1	0.011	0	-9999	-10000	0	0
CSNK1G2	0.011	0	-9999	-10000	0	0
CSNK1G3	0.011	0	-9999	-10000	0	0
MTSS1	0.013	0.018	-9999	-10000	0	0
embryonic limb morphogenesis	-0.068	0.2	-9999	-0.44	104	104
SUFU	0.021	0.018	-9999	-10000	0	0
LGALS3	0.009	0.026	-9999	-0.41	2	2
catabolic process	-0.036	0.13	-9999	-0.28	76	76
GLI3A/CBP	-0.044	0.13	-9999	-0.31	103	103
KIF3A	0.01	0.018	-9999	-0.41	1	1
GLI1	-0.07	0.2	-9999	-0.45	104	104
RAB23	0.007	0.04	-9999	-0.41	5	5
CSNK1A1	0.011	0	-9999	-10000	0	0
IFT172	0.011	0	-9999	-10000	0	0
RBBP7	0.011	0.001	-9999	-10000	0	0
Su(fu)/Galectin3	0.024	0.021	-9999	-0.19	2	2
GNAZ	-0.001	0.069	-9999	-0.41	15	15
RBBP4	0.009	0.031	-9999	-0.41	3	3
CSNK1G1	0.011	0	-9999	-10000	0	0
PIAS1	0.011	0	-9999	-10000	0	0
PRKACA	0.011	0	-9999	-10000	0	0
GLI2/SPOP	-0.006	0.073	-9999	-10000	0	0
STK36	0.012	0.004	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.03	0.1	-9999	-0.27	34	34
PTCH1	-0.055	0.18	-9999	-0.45	66	66
MIM/GLI1	-0.075	0.24	-9999	-0.47	125	125
CREBBP	-0.044	0.13	-9999	-0.31	103	103
Su(fu)/SIN3/HDAC complex	0.038	0.016	-9999	-10000	0	0

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.012	0.044	-9999	-0.23	18	18
EPHB2	0.009	0.025	-9999	-0.33	3	3
Syndecan-2/TACI	0.006	0.051	-9999	-0.2	29	29
LAMA1	-0.1	0.16	-9999	-0.33	182	182
Syndecan-2/alpha2 ITGB1	0.016	0.061	-9999	-0.2	37	37
HRAS	0.011	0	-9999	-10000	0	0
Syndecan-2/CASK	0.006	0.038	-9999	-0.23	13	13
ITGA5	0.011	0	-9999	-10000	0	0
BAX	0.024	0.041	-9999	-10000	0	0
EPB41	0.01	0.018	-9999	-0.41	1	1
positive regulation of cell-cell adhesion	0.013	0.034	-9999	-0.2	13	13
LAMA3	-0.001	0.069	-9999	-0.41	15	15
EZR	0.011	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.024	0.12	-9999	-0.41	45	45
Syndecan-2/MMP2	0.002	0.068	-9999	-0.24	38	38
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	0.009	0.045	-9999	-0.28	13	13
dendrite morphogenesis	0.013	0.04	-9999	-0.22	16	16
Syndecan-2/GM-CSF	0.008	0.046	-9999	-0.22	20	20
determination of left/right symmetry	0.009	0.045	-9999	-0.28	13	13
Syndecan-2/PKC delta	0.014	0.038	-9999	-0.23	13	13
GNB2L1	0.011	0	-9999	-10000	0	0
MAPK3	0.015	0.041	-9999	-0.21	13	13
MAPK1	0.015	0.041	-9999	-0.21	13	13
Syndecan-2/RACK1	0.02	0.032	-9999	-0.18	13	13
NF1	0.009	0.026	-9999	-0.41	2	2
FGFR/FGF/Syndecan-2	0.009	0.045	-9999	-0.28	13	13
ITGA2	0.001	0.065	-9999	-0.41	13	13
MAPK8	0.018	0.046	-9999	-0.22	19	19
Syndecan-2/alpha2/beta1 Integrin	-0.035	0.089	-9999	-0.22	29	29
Syndecan-2/Kininogen	0.001	0.054	-9999	-0.19	37	37
ITGB1	0.011	0	-9999	-10000	0	0
SRC	0.024	0.03	-9999	-0.17	13	13
Syndecan-2/CASK/Protein 4.1	0.013	0.035	-9999	-0.2	14	14
extracellular matrix organization	0.014	0.039	-9999	-0.23	14	14
actin cytoskeleton reorganization	0.012	0.044	-9999	-0.23	18	18
Syndecan-2/Caveolin-2/Ras	0.002	0.072	-9999	-0.21	56	56
Syndecan-2/Laminin alpha3	0.007	0.057	-9999	-0.24	27	27
Syndecan-2/RasGAP	0.022	0.036	-9999	-0.17	18	18
alpha5/beta1 Integrin	0.016	0	-9999	-10000	0	0
PRKCD	0.011	0	-9999	-10000	0	0
Syndecan-2 dimer	0.013	0.04	-9999	-0.22	16	16
GO:0007205	0.003	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.028	0.035	-9999	-0.16	2	2
RHOA	0.011	0	-9999	-10000	0	0
SDCBP	0.011	0	-9999	-10000	0	0
TNFRSF13B	-0.003	0.059	-9999	-0.33	17	17
RASA1	0.007	0.04	-9999	-0.41	5	5
alpha2/beta1 Integrin	0.009	0.045	-9999	-0.28	13	13
Syndecan-2/Synbindin	0.014	0.038	-9999	-0.23	13	13
TGFB1	0.01	0.018	-9999	-0.41	1	1
CASP3	0.02	0.034	-9999	-0.2	13	13
FN1	0.007	0.04	-9999	-0.41	5	5
Syndecan-2/IL8	-0.043	0.093	-9999	-0.18	169	169
SDC2	0.009	0.045	-9999	-0.28	13	13
KNG1	-0.01	0.069	-9999	-0.33	24	24
Syndecan-2/Neurofibromin	0.013	0.041	-9999	-0.23	15	15
TRAPPC4	0.011	0	-9999	-10000	0	0
CSF2	0.001	0.041	-9999	-0.33	8	8
Syndecan-2/TGFB1	0.014	0.039	-9999	-0.23	14	14
Syndecan-2/Syntenin/PI-4-5-P2	0.013	0.034	-9999	-0.2	13	13
Syndecan-2/Ezrin	0.02	0.034	-9999	-0.2	13	13
PRKACA	0.019	0.037	-9999	-0.2	15	15
angiogenesis	-0.042	0.093	-9999	-0.18	169	169
MMP2	-0.01	0.092	-9999	-0.41	27	27
IL8	-0.089	0.16	-9999	-0.33	157	157
calcineurin-NFAT signaling pathway	0.006	0.051	-9999	-0.2	29	29

×

Presenilin action in Notch and Wnt signaling

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
Delta 1/NOTCH/NOTCH(cleaved)	-0.01	0.063	-10000	0	-0.65	4	4
HDAC1	0.008	0.005	-10000	0	-10000	0	0
AES	0.01	0.001	-10000	0	-10000	0	0
FBXW11	0.011	0	-10000	0	-10000	0	0
DTX1	0.006	0.044	-10000	0	-0.41	6	6
LRP6/FZD1	0.015	0.018	-10000	0	-0.28	2	2
TLE1	0.01	0.018	-10000	0	-0.41	1	1
AP1	-0.064	0.12	-10000	0	-0.24	170	170
NCSTN	0.011	0	-10000	0	-10000	0	0
ADAM10	0.008	0.036	-10000	0	-0.41	4	4
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.03	0.052	-10000	0	-0.56	2	2
NICD/RBPSUH	0.023	0.046	-10000	0	-0.5	4	4
WIF1	-0.096	0.16	-10000	0	-0.35	160	160
NOTCH1	-0.004	0.046	-10000	0	-0.53	4	4
PSENEN	0.011	0	-10000	0	-10000	0	0
KREMEN2	-0.021	0.1	-10000	0	-0.33	51	51
DKK1	-0.064	0.14	-10000	0	-0.34	115	115
beta catenin/beta TrCP1	0.026	0.027	-10000	0	-10000	0	0
APH1B	0.006	0.048	-10000	0	-0.41	7	7
APH1A	0.011	0	-10000	0	-10000	0	0
AXIN1	0.001	0.019	-10000	0	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	0.017	0.027	0.19	1	-0.21	3	4
PSEN1	0.011	0	-10000	0	-10000	0	0
FOS	-0.12	0.19	-10000	0	-0.41	165	165
JUN	0.006	0.048	-10000	0	-0.41	7	7
MAP3K7	0.01	0.002	-10000	0	-10000	0	0
CTNNB1	0.02	0.028	-10000	0	-10000	0	0
MAPK3	0.011	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.012	0.083	-10000	0	-0.2	80	80
HNF1A	0.005	0.041	-10000	0	-0.33	8	8
CTBP1	0.01	0.001	-10000	0	-10000	0	0
MYC	-0.004	0.17	-10000	0	-1.3	10	10
NKD1	-0.02	0.1	-10000	0	-0.34	46	46
FZD1	0.009	0.026	-10000	0	-0.41	2	2
NOTCH1 precursor/Deltex homolog 1	0.021	0.05	-10000	0	-0.5	4	4
apoptosis	-0.064	0.12	-10000	0	-0.24	170	170
Delta 1/NOTCHprecursor	0.017	0.066	-10000	0	-0.64	4	4
DLL1	-0.002	0.074	-10000	0	-0.41	17	17
PPARD	0.018	0.013	-10000	0	-10000	0	0
Gamma Secretase	0.031	0.024	-10000	0	-0.18	7	7
APC	0.001	0.019	-10000	0	-0.18	4	4
DVL1	0	0.015	-10000	0	-10000	0	0
CSNK2A1	0.011	0.001	-10000	0	-10000	0	0
MAP3K7IP1	-0.001	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.039	0.096	-10000	0	-0.18	159	159
LRP6	0.011	0	-10000	0	-10000	0	0
CSNK1A1	0.011	0.001	-10000	0	-10000	0	0
NLK	0.011	0.006	-10000	0	-10000	0	0
CCND1	0.018	0.019	-10000	0	-10000	0	0
WNT1	0.004	0.041	-10000	0	-0.33	8	8
Axin1/APC/beta catenin	0.029	0.025	-10000	0	-10000	0	0
DKK2	-0.016	0.1	-10000	0	-0.4	34	34
NOTCH1 precursor/DVL1	0	0.04	-10000	0	-0.46	4	4
GSK3B	0.011	0	-10000	0	-10000	0	0
FRAT1	0.01	0.001	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.006	0.048	-10000	0	-0.51	4	4
PPP2R5D	0.011	0.046	0.16	39	-10000	0	39
MAPK1	0.011	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.032	0.089	-10000	0	-0.21	38	38
RBPJ	0.011	0	-10000	0	-10000	0	0
CREBBP	0.012	0.026	-10000	0	-0.41	2	2

×

Glucocorticoid receptor regulatory network

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
PCK2	-0.01	0.04	-10000	0	-10000	0	0
SMARCC2	0.012	0.002	-10000	0	-10000	0	0
SMARCC1	0.012	0.003	-10000	0	-10000	0	0
TBX21	0.006	0.12	-10000	0	-0.72	9	9
SUMO2	0.01	0.005	-10000	0	-10000	0	0
STAT1 (dimer)	0.017	0.015	-10000	0	-0.32	1	1
FKBP4	0.011	0	-10000	0	-10000	0	0
FKBP5	0.005	0.051	-10000	0	-0.41	8	8
GR alpha/HSP90/FKBP51/HSP90	0.001	0.1	0.21	13	-0.25	54	67
PRL	-0.029	0.25	-10000	0	-1.2	20	20
cortisol/GR alpha (dimer)/TIF2	0.027	0.16	0.43	23	-0.42	8	31
RELA	-0.015	0.062	-10000	0	-0.23	9	9
FGG	0.005	0.14	0.37	14	-0.48	4	18
GR beta/TIF2	-0.015	0.13	0.22	13	-0.31	66	79
IFNG	-0.094	0.14	-10000	0	-0.5	12	12
apoptosis	-0.078	0.19	0.47	8	-0.57	31	39
CREB1	0.008	0.022	-10000	0	-10000	0	0
histone acetylation	0.038	0.075	0.24	9	-0.24	9	18
BGLAP	0.025	0.065	-10000	0	-10000	0	0
GR/PKAc	0.005	0.093	0.21	8	-0.24	36	44
NF kappa B1 p50/RelA	-0.024	0.11	-10000	0	-0.33	29	29
SMARCD1	0.012	0.003	-10000	0	-10000	0	0
MDM2	0.022	0.041	0.18	15	-10000	0	15
GATA3	0.001	0.07	-10000	0	-0.35	20	20
AKT1	0.005	0.002	-10000	0	-10000	0	0
CSF2	0.018	0.066	-10000	0	-10000	0	0
GSK3B	0.01	0.005	-10000	0	-10000	0	0
NR1I3	-0.056	0.17	0.46	7	-0.54	23	30
CSN2	0.003	0.11	0.31	13	-0.36	4	17
BRG1/BAF155/BAF170/BAF60A	0.035	0.009	-10000	0	-10000	0	0
NFATC1	0.002	0.069	-10000	0	-0.41	15	15
POU2F1	0.007	0.044	-10000	0	-0.23	16	16
CDKN1A	0.032	0.06	-10000	0	-1.3	1	1
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.001	0.006	-10000	0	-10000	0	0
SFN	-0.24	0.15	-10000	0	-0.33	395	395
GR alpha/HSP90/FKBP51/HSP90/14-3-3	-0.11	0.14	0.22	15	-0.33	80	95
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.11	0.29	0.44	7	-0.81	70	77
JUN	-0.041	0.1	-10000	0	-0.36	15	15
IL4	0.006	0.08	-10000	0	-0.56	1	1
CDK5R1	0.01	0.015	-10000	0	-0.33	1	1
PRKACA	0.011	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.18	0.17	-10000	0	-0.37	187	187
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.009	0.095	0.21	12	-0.23	45	57
cortisol/GR alpha (monomer)	0.029	0.18	0.49	24	-0.47	4	28
NCOA2	-0.004	0.078	-10000	0	-0.41	19	19
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.15	0.2	-10000	0	-0.44	165	165
AP-1/NFAT1-c-4	-0.16	0.18	-10000	0	-0.5	57	57
AFP	-0.016	0.08	-10000	0	-10000	0	0
SUV420H1	0.011	0	-10000	0	-10000	0	0
IRF1	0.026	0.089	0.31	6	-10000	0	6
TP53	0.027	0.028	-10000	0	-0.42	2	2
PPP5C	0.011	0	-10000	0	-10000	0	0
KRT17	-0.12	0.19	-10000	0	-0.75	17	17
KRT14	-0.052	0.11	0.43	1	-10000	0	1
TBP	0.019	0	-10000	0	-10000	0	0
CREBBP	0.031	0.046	-10000	0	-0.32	4	4
HDAC1	0.01	0.002	-10000	0	-10000	0	0
HDAC2	0.01	0.002	-10000	0	-10000	0	0
AP-1	-0.16	0.18	-10000	0	-0.5	58	58
MAPK14	0.01	0.005	-10000	0	-10000	0	0
MAPK10	-0.08	0.17	-10000	0	-0.41	115	115
MAPK11	0.008	0.026	-10000	0	-0.41	2	2
KRT5	-0.14	0.21	-10000	0	-0.71	31	31
interleukin-1 receptor activity	-0.001	0.002	-10000	0	-10000	0	0
NCOA1	0.012	0.018	-10000	0	-0.41	1	1
STAT1	0.017	0.015	-10000	0	-0.32	1	1
CGA	0.005	0.082	-10000	0	-0.38	2	2
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.009	0.098	0.27	6	-0.41	3	9
MAPK3	0.01	0.006	-10000	0	-10000	0	0
MAPK1	0.01	0.005	-10000	0	-10000	0	0
ICAM1	-0.015	0.11	-10000	0	-0.39	11	11
NFKB1	-0.016	0.064	-10000	0	-0.25	8	8
MAPK8	-0.017	0.098	0.26	1	-0.33	15	16
MAPK9	0.01	0.005	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.085	0.2	0.47	8	-0.6	31	39
BAX	0.034	0.025	-10000	0	-10000	0	0
POMC	-0.019	0.21	-10000	0	-1.3	10	10
EP300	0.032	0.037	-10000	0	-0.23	2	2
cortisol/GR alpha (dimer)/p53	0.046	0.16	0.44	24	-0.46	2	26
proteasomal ubiquitin-dependent protein catabolic process	0.011	0.033	0.14	8	-10000	0	8
SGK1	0.045	0.093	-10000	0	-1.3	2	2
IL13	-0.059	0.11	-10000	0	-0.52	6	6
IL6	-0.037	0.19	-10000	0	-0.77	23	23
PRKACG	0.003	0.005	-10000	0	-10000	0	0
IL5	-0.056	0.097	-10000	0	-0.58	2	2
IL2	-0.089	0.13	-10000	0	-0.5	9	9
CDK5	0.01	0.003	-10000	0	-10000	0	0
PRKACB	0.006	0.044	-10000	0	-0.41	6	6
HSP90AA1	0.011	0	-10000	0	-10000	0	0
IL8	-0.051	0.13	-10000	0	-0.44	12	12
CDK5R1/CDK5	0.014	0.013	-10000	0	-0.22	1	1
NF kappa B1 p50/RelA/PKAc	-0.001	0.085	-10000	0	-0.3	12	12
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.043	0.14	0.41	24	-0.42	2	26
SMARCA4	0.012	0.002	-10000	0	-10000	0	0
chromatin remodeling	0.026	0.11	0.29	15	-0.43	4	19
NF kappa B1 p50/RelA/Cbp	0.021	0.1	-10000	0	-0.34	9	9
JUN (dimer)	-0.041	0.1	-10000	0	-0.36	15	15
YWHAH	0.011	0	-10000	0	-10000	0	0
VIPR1	0.012	0.089	-10000	0	-0.32	15	15
NR3C1	-0.015	0.16	0.32	13	-0.4	64	77
NR4A1	-0.023	0.12	-10000	0	-0.43	44	44
TIF2/SUV420H1	0.006	0.055	-10000	0	-0.28	19	19
MAPKKK cascade	-0.078	0.19	0.47	8	-0.57	31	39
cortisol/GR alpha (dimer)/Src-1	0.04	0.15	0.43	24	-0.42	3	27
PBX1	-0.009	0.095	-10000	0	-0.34	37	37
POU1F1	-0.003	0.049	-10000	0	-0.25	19	19
SELE	-0.098	0.32	-10000	0	-0.93	64	64
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.026	0.11	0.29	15	-0.43	4	19
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.043	0.14	0.41	24	-0.42	2	26
mol:cortisol	0.024	0.076	0.28	21	-10000	0	21
MMP1	-0.12	0.11	-10000	0	-10000	0	0

×

Calcium signaling in the CD4+ TCR 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
NFATC1	0.008	0.045	-9999	-0.24	15	15
NFATC2	-0.01	0.078	-9999	-0.24	53	53
NFATC3	0.015	0.018	-9999	-10000	0	0
CD40LG	-0.055	0.18	-9999	-0.51	39	39
PTGS2	-0.074	0.21	-9999	-0.49	74	74
JUNB	0.007	0.04	-9999	-0.41	5	5
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.001	0.007	-9999	-10000	0	0
CaM/Ca2+	-0.001	0.007	-9999	-10000	0	0
CALM1	0.011	0.005	-9999	-10000	0	0
JUN	0.006	0.048	-9999	-0.41	7	7
mol:Ca2+	-0.002	0.007	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.004	0.004	-9999	-10000	0	0
FOSL1	-0.014	0.089	-9999	-0.33	40	40
CREM	0.011	0.001	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.036	0.081	-9999	-0.33	19	19
FOS	-0.12	0.19	-9999	-0.41	165	165
IFNG	-0.066	0.19	-9999	-0.48	56	56
AP-1/NFAT1-c-4	-0.062	0.2	-9999	-0.53	43	43
FASLG	-0.054	0.18	-9999	-0.52	36	36
NFAT1-c-4/ICER1	-0.01	0.081	-9999	-0.27	23	23
IL2RA	-0.055	0.18	-9999	-0.51	40	40
FKBP12/FK506	0.008	0	-9999	-10000	0	0
CSF2	-0.055	0.17	-9999	-0.49	37	37
JunB/Fra1/NFAT1-c-4	-0.022	0.084	-9999	-0.28	23	23
IL4	-0.055	0.17	-9999	-0.5	32	32
IL2	-0.009	0.031	-9999	-10000	0	0
IL3	-0.011	0.015	-9999	-10000	0	0
FKBP1A	0.011	0	-9999	-10000	0	0
BATF3	0.01	0.015	-9999	-0.33	1	1
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.011	0	-9999	-10000	0	0

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.1	0.19	-10000	0	-0.41	147	147
HRAS	0.011	0	-10000	0	-10000	0	0
EGFR	0	0.066	-10000	0	-0.4	14	14
AKT	-0.068	0.13	-10000	0	-0.28	108	108
FOXO3	0.011	0	-10000	0	-10000	0	0
AKT1	0.011	0	-10000	0	-10000	0	0
FOXO1	0.009	0.031	-10000	0	-0.41	3	3
AKT3	-0.15	0.2	-10000	0	-0.41	202	202
FOXO4	0.009	0.026	-10000	0	-0.41	2	2
MET	0.005	0.046	-10000	0	-0.37	8	8
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
PIK3CB	0.011	0	-10000	0	-10000	0	0
NRAS	0.011	0	-10000	0	-10000	0	0
PIK3CG	-0.001	0.07	-10000	0	-0.4	16	16
PIK3R3	0.01	0.015	-10000	0	-0.33	1	1
PIK3R2	0.011	0	-10000	0	-10000	0	0
NF1	0.009	0.026	-10000	0	-0.41	2	2
RAS	-0.022	0.073	0.18	1	-0.26	14	15
ERBB2	0.002	0.054	-10000	0	-0.33	14	14
proliferation/survival/translation	0.011	0.066	0.22	20	-10000	0	20
PI3K	-0.013	0.074	0.15	2	-0.21	27	29
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
KRAS	0.01	0.015	-10000	0	-0.33	1	1
FOXO	0.023	0.022	-10000	0	-10000	0	0
AKT2	0.011	0	-10000	0	-10000	0	0
PTEN	0.006	0.044	-10000	0	-0.41	6	6

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.009	0.036	-9999	-0.41	4	4
ELF1	0.009	0.046	-9999	-0.38	5	5
CCNA2	-0.061	0.14	-9999	-0.33	114	114
PIK3CA	0.011	0.018	-9999	-0.41	1	1
JAK3	0.009	0.029	-9999	-0.33	4	4
PIK3R1	0.008	0.04	-9999	-0.41	5	5
JAK1	0.01	0.026	-9999	-0.41	2	2
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.053	0.045	-9999	-0.51	1	1
SHC1	0.012	0	-9999	-10000	0	0
SP1	-0.043	0.12	-9999	-0.3	101	101
IL2RA	0.013	0.06	-9999	-0.65	1	1
IL2RB	0.011	0.018	-9999	-0.41	1	1
SOS1	0.012	0	-9999	-10000	0	0
IL2RG	0.006	0.047	-9999	-0.36	9	9
G1/S transition of mitotic cell cycle	-0.1	0.27	-9999	-0.64	102	102
PTPN11	0.012	0	-9999	-10000	0	0
CCND2	-0.1	0.26	-9999	-0.65	101	101
LCK	0.008	0.034	-9999	-0.34	5	5
GRB2	0.012	0	-9999	-10000	0	0
IL2	-0.006	0.06	-9999	-0.33	18	18
CDK6	0.001	0.065	-9999	-0.41	13	13
CCND3	0.056	0.041	-9999	-0.43	1	1

×

BCR signaling 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
JUN	0.015	0.085	-10000	0	-0.29	31	31
IKBKB	0.027	0.048	0.16	1	-0.17	2	3
AKT1	0.004	0.066	0.19	4	-0.2	28	32
IKBKG	0.029	0.049	-10000	0	-0.18	1	1
CALM1	0.02	0.079	0.18	4	-0.25	20	24
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
MAP3K1	0.005	0.11	-10000	0	-0.43	26	26
MAP3K7	0.011	0	-10000	0	-10000	0	0
mol:Ca2+	0.015	0.082	0.18	65	-0.27	20	85
DOK1	0.011	0	-10000	0	-10000	0	0
AP-1	-0.001	0.077	0.14	40	-0.19	30	70
LYN	0.011	0	-10000	0	-10000	0	0
BLNK	0.009	0.029	-10000	0	-0.38	3	3
SHC1	0.011	0	-10000	0	-10000	0	0
BCR complex	-0.023	0.096	-10000	0	-0.24	82	82
CD22	-0.06	0.13	-10000	0	-0.5	32	32
CAMK2G	0.025	0.075	0.18	3	-0.23	20	23
CSNK2A1	0.011	0	-10000	0	-10000	0	0
INPP5D	0.01	0.018	-10000	0	-0.41	1	1
SHC/GRB2/SOS1	-0.019	0.047	-10000	0	-0.3	3	3
GO:0007205	0.015	0.083	0.18	65	-0.27	20	85
SYK	0.01	0.015	-10000	0	-0.33	1	1
ELK1	0.02	0.079	0.18	4	-0.25	20	24
NFATC1	0.004	0.1	0.18	3	-0.32	35	38
B-cell antigen/BCR complex	-0.023	0.096	-10000	0	-0.24	82	82
PAG1/CSK	0.015	0.022	-10000	0	-0.28	3	3
NFKBIB	0.019	0.021	0.083	1	-0.12	1	2
HRAS	0.02	0.071	0.19	1	-0.23	20	21
NFKBIA	0.019	0.021	0.083	1	-0.12	1	2
NF-kappa-B/RelA/I kappa B beta	0.022	0.02	0.084	1	-0.14	1	2
RasGAP/Csk	0.001	0.074	-10000	0	-0.2	35	35
mol:GDP	0.014	0.079	0.18	6	-0.25	21	27
PTEN	0.006	0.044	-10000	0	-0.41	6	6
CD79B	-0.009	0.088	-10000	0	-0.41	25	25
NF-kappa-B/RelA/I kappa B alpha	0.022	0.02	0.084	1	-0.14	1	2
GRB2	0.011	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	0.008	0.12	-10000	0	-0.43	30	30
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
mol:IP3	0.015	0.083	0.18	65	-0.27	20	85
CSK	0.011	0	-10000	0	-10000	0	0
FOS	-0.031	0.12	0.21	1	-0.25	44	45
CHUK	0.029	0.049	0.16	1	-0.18	3	4
IBTK	0.011	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.013	0.047	-10000	0	-0.3	5	5
PTPN6	-0.033	0.14	-10000	0	-0.48	31	31
RELA	0.011	0	-10000	0	-10000	0	0
BCL2A1	0.019	0.016	-10000	0	-10000	0	0
VAV2	-0.009	0.12	-10000	0	-0.44	27	27
ubiquitin-dependent protein catabolic process	0.022	0.021	0.085	1	-0.12	1	2
BTK	-0.005	0.065	-10000	0	-1.1	2	2
CD19	-0.04	0.11	-10000	0	-0.33	52	52
MAP4K1	0.003	0.052	-10000	0	-0.33	13	13
CD72	0.009	0.025	-10000	0	-0.33	3	3
PAG1	0.009	0.031	-10000	0	-0.41	3	3
MAPK14	0.012	0.096	-10000	0	-0.37	26	26
SH3BP5	-0.049	0.15	-10000	0	-0.41	77	77
PIK3AP1	0.021	0.092	0.2	62	-0.3	20	82
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	0.014	0.054	-10000	0	-0.34	5	5
RAF1	0.025	0.068	0.19	1	-0.31	3	4
RasGAP/p62DOK/SHIP	-0.024	0.058	-10000	0	-0.3	5	5
CD79A	-0.027	0.11	-10000	0	-0.34	59	59
re-entry into mitotic cell cycle	0	0.076	0.14	40	-0.19	30	70
RASA1	0.007	0.04	-10000	0	-0.41	5	5
MAPK3	0.033	0.061	0.18	1	-0.26	3	4
MAPK1	0.033	0.061	0.18	1	-0.26	3	4
CD72/SHP1	-0.026	0.13	-10000	0	-0.45	31	31
NFKB1	0.01	0.018	-10000	0	-0.41	1	1
MAPK8	0.01	0.099	-10000	0	-0.36	30	30
actin cytoskeleton organization	0	0.1	-10000	0	-0.38	26	26
NF-kappa-B/RelA	0.047	0.038	0.16	1	-0.18	1	2
Calcineurin	-0.011	0.045	-10000	0	-0.31	5	5
PI3K	-0.046	0.094	-10000	0	-0.36	32	32
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	0.019	0.094	0.2	64	-0.31	20	84
SOS1	0.011	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.024	0.17	-10000	0	-0.64	34	34
DAPP1	-0.049	0.18	-10000	0	-0.72	34	34
cytokine secretion	0.005	0.097	0.18	3	-0.3	35	38
mol:DAG	0.015	0.083	0.18	65	-0.27	20	85
PLCG2	0.01	0.023	-10000	0	-0.37	2	2
MAP2K1	0.029	0.065	0.19	1	-0.29	3	4
B-cell antigen/BCR complex/FcgammaRIIB	-0.013	0.084	-10000	0	-0.2	84	84
mol:PI-3-4-5-P3	-0.034	0.073	0.21	5	-0.26	32	37
ETS1	0.029	0.072	0.2	1	-0.3	3	4
B-cell antigen/BCR complex/LYN/SYK/BLNK	0.003	0.071	-10000	0	-0.2	30	30
B-cell antigen/BCR complex/LYN	-0.033	0.1	-10000	0	-0.45	28	28
MALT1	0.011	0	-10000	0	-10000	0	0
TRAF6	0.011	0	-10000	0	-10000	0	0
RAC1	-0.001	0.11	-10000	0	-0.41	26	26
B-cell antigen/BCR complex/LYN/SYK	-0.054	0.12	-10000	0	-0.46	30	30
CARD11	0.016	0.084	0.17	63	-0.26	21	84
FCGR2B	0.008	0.035	-10000	0	-0.39	4	4
PPP3CA	0.011	0	-10000	0	-10000	0	0
BCL10	0.011	0	-10000	0	-10000	0	0
IKK complex	0.019	0.024	0.11	1	-10000	0	1
PTPRC	0.003	0.059	-10000	0	-0.4	11	11
PDPK1	-0.001	0.062	0.17	4	-0.18	29	33
PPP3CB	0.011	0	-10000	0	-10000	0	0
PPP3CC	0.008	0.036	-10000	0	-0.41	4	4
POU2F2	0.02	0.015	-10000	0	-0.1	1	1

×

Insulin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.074	0.11	-9999	-0.36	37	37
TC10/GTP	-0.054	0.075	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	0.001	0.069	-9999	-0.21	53	53
HRAS	0.011	0	-9999	-10000	0	0
APS homodimer	0.011	0	-9999	-10000	0	0
GRB14	-0.11	0.16	-9999	-0.33	195	195
FOXO3	-0.01	0.037	-9999	-0.57	2	2
AKT1	-0.031	0.091	-9999	-0.28	28	28
INSR	0.012	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0.03	0.002	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.01	0.018	-9999	-0.41	1	1
SORBS1	-0.13	0.2	-9999	-0.41	183	183
CRK	0.011	0	-9999	-10000	0	0
PTPN1	0.027	0.001	-9999	-10000	0	0
CAV1	-0.036	0.11	-9999	-0.23	125	125
CBL/APS/CAP/Crk-II/C3G	-0.039	0.1	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/NCK2	0.001	0.069	-9999	-0.21	53	53
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.019	0.057	-9999	-0.18	49	49
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.013	0.054	-9999	-10000	0	0
RPS6KB1	-0.023	0.086	-9999	-0.25	28	28
PARD6A	0.011	0	-9999	-10000	0	0
CBL	0.011	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0.003	-9999	-10000	0	0
PIK3R1	0.007	0.04	-9999	-0.41	5	5
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.047	0.066	-9999	-0.26	28	28
HRAS/GTP	-0.014	0.043	-9999	-10000	0	0
Insulin Receptor	0.012	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.008	0.064	-9999	-0.19	53	53
PRKCI	-0.012	0.018	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.059	0.08	-9999	-0.3	28	28
SHC1	0.011	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	-0.002	0.028	-9999	-0.39	2	2
PI3K	-0.019	0.058	-9999	-0.18	49	49
NCK2	0.011	0	-9999	-10000	0	0
RHOQ	0.011	0	-9999	-10000	0	0
mol:H2O2	0	0	-9999	-10000	0	0
HRAS/GDP	0.008	0	-9999	-10000	0	0
AKT2	-0.031	0.091	-9999	-0.28	28	28
PRKCZ	-0.013	0.028	-9999	-0.52	1	1
SH2B2	0.011	0	-9999	-10000	0	0
SHC/SHIP	0.007	0.061	-9999	-0.18	54	54
F2RL2	-0.016	0.1	-9999	-0.4	35	35
TRIP10	0.011	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	0.017	0.002	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.015	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.029	0.001	-9999	-10000	0	0
RAPGEF1	0.011	0	-9999	-10000	0	0
RASA1	0.007	0.04	-9999	-0.41	5	5
NCK1	0.009	0.026	-9999	-0.41	2	2
CBL/APS/CAP/Crk-II	-0.049	0.11	-9999	-0.2	183	183
TC10/GDP	0.008	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.024	0.01	-9999	-0.21	1	1
INPP5D	0	0.064	-9999	-0.19	54	54
SOS1	0.011	0	-9999	-10000	0	0
SGK1	-0.006	0.05	-9999	-0.82	2	2
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.011	0	-9999	-10000	0	0
IRS1	-0.03	0.12	-9999	-0.41	53	53
p62DOK/RasGAP	-0.002	0.028	-9999	-0.39	2	2
INS	0.003	0.002	-9999	-10000	0	0
mol:PI-3-4-P2	0	0.064	-9999	-0.19	54	54
GRB2	0.011	0	-9999	-10000	0	0
EIF4EBP1	-0.027	0.09	-9999	-0.26	32	32
PTPRA	0.012	0	-9999	-10000	0	0
PIK3CA	0.01	0.018	-9999	-0.41	1	1
TC10/GTP/CIP4	0.015	0	-9999	-10000	0	0
PDPK1	0.011	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.006	0.064	-9999	-0.19	46	46
Insulin Receptor/Insulin/IRS1	-0.006	0.069	-9999	-0.21	53	53
Insulin Receptor/Insulin/IRS3	0.012	0.002	-9999	-10000	0	0
Par3/Par6	0.013	0.051	-9999	-0.18	32	32

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.018	0.001	-9999	-10000	0	0
SMARCC1	0.006	0.016	-9999	-10000	0	0
REL	0.011	0.001	-9999	-10000	0	0
HDAC7	0.02	0.066	-9999	-0.28	3	3
JUN	0.006	0.048	-9999	-0.41	7	7
EP300	0.011	0	-9999	-10000	0	0
KAT2B	0.004	0.054	-9999	-0.41	9	9
KAT5	0.011	0	-9999	-10000	0	0
MAPK14	-0.01	0.079	-9999	-0.21	69	69
FOXO1	0.009	0.031	-9999	-0.41	3	3
T-DHT/AR	0.019	0.071	-9999	-0.3	3	3
MAP2K6	-0.032	0.11	-9999	-0.33	69	69
BRM/BAF57	0.008	0.05	-9999	-0.28	16	16
MAP2K4	0.011	0.018	-9999	-0.41	1	1
SMARCA2	-0.001	0.071	-9999	-0.41	16	16
PDE9A	-0.02	0.1	-9999	-0.96	4	4
NCOA2	-0.004	0.078	-9999	-0.41	19	19
CEBPA	0.007	0.037	-9999	-0.38	5	5
EHMT2	0.011	0.001	-9999	-10000	0	0
cell proliferation	0.012	0.11	-9999	-0.37	19	19
NR0B1	-0.014	0.076	-9999	-0.33	29	29
EGR1	-0.044	0.14	-9999	-0.41	70	70
RXRs/9cRA	-0.01	0.077	-9999	-0.2	69	69
AR/RACK1/Src	0.009	0.069	-9999	-0.29	5	5
AR/GR	-0.047	0.12	-9999	-0.25	103	103
GNB2L1	0.011	0.002	-9999	-10000	0	0
PKN1	0.011	0	-9999	-10000	0	0
RCHY1	0.011	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0.002	-9999	-10000	0	0
MAPK8	0.016	0.034	-9999	-0.28	7	7
T-DHT/AR/TIF2/CARM1	0.004	0.083	-9999	-0.32	14	14
SRC	0.011	0.061	-9999	-0.28	2	2
NR3C1	-0.051	0.15	-9999	-0.41	79	79
KLK3	-0.048	0.091	-9999	-0.41	8	8
APPBP2	0.012	0.002	-9999	-10000	0	0
TRIM24	0.011	0.002	-9999	-10000	0	0
T-DHT/AR/TIP60	0.004	0.063	-9999	-0.36	2	2
TMPRSS2	-0.031	0.14	-9999	-1	8	8
RXRG	-0.048	0.14	-9999	-0.4	77	77
mol:9cRA	0	0	-9999	-10000	0	0
RXRA	0.011	0	-9999	-10000	0	0
RXRB	0.011	0	-9999	-10000	0	0
CARM1	0.011	0.002	-9999	-10000	0	0
NR2C2	0.002	0.059	-9999	-0.41	11	11
KLK2	-0.011	0.16	-9999	-0.56	33	33
AR	-0.022	0.098	-9999	-0.22	90	90
SENP1	0.011	0	-9999	-10000	0	0
HSP90AA1	0.011	0	-9999	-10000	0	0
MDM2	0.011	0.002	-9999	-10000	0	0
SRY	0	0.002	-9999	-10000	0	0
GATA2	-0.029	0.12	-9999	-0.41	51	51
MYST2	0.011	0	-9999	-10000	0	0
HOXB13	-0.22	0.16	-9999	-0.33	360	360
T-DHT/AR/RACK1/Src	0.009	0.065	-9999	-0.31	3	3
positive regulation of transcription	-0.029	0.12	-9999	-0.41	51	51
DNAJA1	0.012	0.002	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.023	0.001	-9999	-10000	0	0
NCOA1	0.013	0.02	-9999	-0.44	1	1
SPDEF	-0.11	0.17	-9999	-0.34	186	186
T-DHT/AR/TIF2	0.011	0.073	-9999	-0.29	16	16
T-DHT/AR/Hsp90	0.004	0.063	-9999	-0.36	2	2
GSK3B	0.012	0.002	-9999	-10000	0	0
NR2C1	0.011	0	-9999	-10000	0	0
mol:T-DHT	0.006	0.065	-9999	-0.22	7	7
SIRT1	0.009	0.026	-9999	-0.41	2	2
ZMIZ2	0.011	0.002	-9999	-10000	0	0
POU2F1	0.021	0.011	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.008	0.072	-9999	-0.31	5	5
CREBBP	0.009	0.026	-9999	-0.41	2	2
SMARCE1	0.011	0.001	-9999	-10000	0	0

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.033	0.13	-10000	0	-0.5	6	6
CRP	0.027	0.13	-10000	0	-0.51	7	7
cell cycle arrest	0.027	0.14	-10000	0	-0.53	10	10
TIMP1	0.029	0.12	-10000	0	-0.48	9	9
IL6ST	-0.048	0.15	-10000	0	-0.41	81	81
Rac1/GDP	0	0.12	-10000	0	-0.35	36	36
AP1	-0.021	0.12	-10000	0	-0.52	10	10
GAB2	0.009	0.036	-10000	0	-0.41	4	4
TNFSF11	0.014	0.14	-10000	0	-0.53	6	6
HSP90B1	0.032	0.03	-10000	0	-10000	0	0
GAB1	0.008	0.036	-10000	0	-0.41	4	4
MAPK14	-0.026	0.13	-10000	0	-0.38	39	39
AKT1	0.042	0.039	-10000	0	-0.39	2	2
FOXO1	0.045	0.04	-10000	0	-0.37	2	2
MAP2K6	-0.031	0.14	-10000	0	-0.38	44	44
mol:GTP	0	0.001	-10000	0	-10000	0	0
MAP2K4	0.016	0.12	-10000	0	-0.38	20	20
MITF	-0.03	0.15	-10000	0	-0.39	55	55
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.011	0	-10000	0	-10000	0	0
A2M	0.012	0.078	-10000	0	-1.3	2	2
CEBPB	0.017	0.002	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.013	0.085	-10000	0	-0.57	6	6
STAT3	0.029	0.14	-10000	0	-0.56	10	10
STAT1	0.002	0.014	-10000	0	-10000	0	0
CEBPD	0.032	0.13	-10000	0	-0.6	6	6
PIK3CA	0.012	0.018	-10000	0	-0.41	1	1
PI3K	0.015	0.031	-10000	0	-0.28	6	6
JUN	0.006	0.048	-10000	0	-0.41	7	7
PIAS3/MITF	-0.023	0.14	-10000	0	-0.37	55	55
MAPK11	-0.026	0.13	-10000	0	-0.38	39	39
STAT3 (dimer)/FOXO1	0.062	0.13	-10000	0	-0.46	7	7
GRB2/SOS1/GAB family	-0.042	0.1	0.14	1	-0.36	33	34
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.019	0.13	-10000	0	-0.37	41	41
GRB2	0.012	0.001	-10000	0	-10000	0	0
JAK2	0.004	0.054	-10000	0	-0.41	9	9
LBP	0.019	0.12	-10000	0	-0.52	2	2
PIK3R1	0.008	0.04	-10000	0	-0.41	5	5
JAK1	0.012	0.026	-10000	0	-0.4	2	2
MYC	0.022	0.18	-10000	0	-0.86	13	13
FGG	0.026	0.13	-10000	0	-0.55	4	4
macrophage differentiation	0.027	0.14	-10000	0	-0.53	10	10
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.04	0.12	-10000	0	-0.38	36	36
JUNB	0.026	0.15	-10000	0	-0.76	8	8
FOS	-0.12	0.19	-10000	0	-0.41	165	165
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.017	0.13	-10000	0	-0.39	38	38
STAT1/PIAS1	0.002	0.12	-10000	0	-0.33	35	35
GRB2/SOS1/GAB family/SHP2/PI3K	0.033	0.041	-10000	0	-0.3	5	5
STAT3 (dimer)	0.029	0.14	-10000	0	-0.55	10	10
PRKCD	0.03	0.12	-10000	0	-0.44	11	11
IL6R	-0.023	0.12	-10000	0	-0.41	46	46
SOCS3	-0.026	0.14	-10000	0	-0.61	11	11
gp130 (dimer)/JAK1/JAK1/LMO4	-0.006	0.092	-10000	0	-0.22	83	83
Rac1/GTP	0.003	0.12	-10000	0	-0.35	36	36
HCK	0.006	0.039	-10000	0	-0.33	7	7
MAPKKK cascade	0.026	0.081	-10000	0	-0.77	4	4
bone resorption	0.014	0.13	-10000	0	-0.51	6	6
IRF1	0.033	0.12	-10000	0	-0.5	6	6
mol:GDP	-0.009	0.13	-10000	0	-0.37	37	37
SOS1	0.011	0.001	-10000	0	-10000	0	0
VAV1	-0.009	0.13	-10000	0	-0.38	37	37
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.038	0.16	-10000	0	-0.46	49	49
PTPN11	0.002	0.014	-10000	0	-10000	0	0
IL6/IL6RA	-0.015	0.1	-10000	0	-0.29	65	65
gp130 (dimer)/TYK2/TYK2/LMO4	-0.009	0.09	-10000	0	-0.22	81	81
gp130 (dimer)/JAK2/JAK2/LMO4	-0.013	0.096	-10000	0	-0.23	88	88
IL6	-0.003	0.083	-10000	0	-0.38	25	25
PIAS3	0.011	0	-10000	0	-10000	0	0
PTPRE	0.003	0.024	-10000	0	-0.37	2	2
PIAS1	0.011	0	-10000	0	-10000	0	0
RAC1	0.011	0.001	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.028	0.13	-10000	0	-0.32	58	58
LMO4	0.015	0.005	-10000	0	-10000	0	0
STAT3 (dimer)/PIAS3	0.019	0.13	-10000	0	-0.54	10	10
MCL1	0.046	0.036	-10000	0	-10000	0	0

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.16	0.2	-9999	-0.41	214	214
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.01	0.015	-9999	-0.33	1	1
TCEB1	0.011	0	-9999	-10000	0	0
HIF1A/p53	0.025	0.01	-9999	-0.17	1	1
HIF1A	0.02	0.005	-9999	-10000	0	0
COPS5	0.011	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.032	0.012	-9999	-10000	0	0
FIH (dimer)	0.011	0	-9999	-10000	0	0
CDKN2A	-0.13	0.17	-9999	-0.33	225	225
ARNT/IPAS	-0.1	0.14	-9999	-0.28	214	214
HIF1AN	0.011	0	-9999	-10000	0	0
GNB2L1	0.011	0	-9999	-10000	0	0
HIF1A/ARNT	0.026	0.005	-9999	-10000	0	0
CUL2	0.011	0	-9999	-10000	0	0
OS9	0.011	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	0.022	0.008	-9999	-0.17	1	1
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.026	0.005	-9999	-10000	0	0
PHD1-3/OS9	0.027	0.016	-9999	-0.2	1	1
HIF1A/RACK1/Elongin B/Elongin C	0.034	0.008	-9999	-10000	0	0
VHL	0.01	0.018	-9999	-0.41	1	1
HSP90AA1	0.011	0	-9999	-10000	0	0
HIF1A/JAB1	0.026	0.005	-9999	-10000	0	0
EGLN3	0.008	0.031	-9999	-0.35	4	4
EGLN2	0.011	0	-9999	-10000	0	0
EGLN1	0.011	0	-9999	-10000	0	0
TP53	0.01	0.018	-9999	-0.41	1	1
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.03	0.023	-9999	-0.5	1	1
ARNT	0.011	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.011	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.037	0.074	-9999	-0.19	1	1

×

Retinoic acid receptors-mediated signaling

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
HDAC1	0.011	0	-10000	0	-10000	0	0
HDAC3	0.011	0	-10000	0	-10000	0	0
VDR	0.003	0.052	-10000	0	-0.33	13	13
Cbp/p300/PCAF	0.017	0.035	-10000	0	-0.23	11	11
EP300	0.011	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.02	0.051	-10000	0	-0.28	7	7
KAT2B	0.004	0.054	-10000	0	-0.41	9	9
MAPK14	0.011	0	-10000	0	-10000	0	0
AKT1	0.011	0.06	0.19	20	-0.24	12	32
RAR alpha/9cRA/Cyclin H	-0.02	0.065	-10000	0	-0.24	39	39
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.016	0.056	-10000	0	-0.25	13	13
CDC2	0	0.001	-10000	0	-10000	0	0
response to UV	0.001	0.002	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.005	0.068	-10000	0	-0.2	47	47
NCOR2	0.011	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.003	0.036	-10000	0	-0.23	13	13
RXRs/RARs/NRIP1/9cRA	-0.003	0.13	-10000	0	-0.4	45	45
NCOA2	-0.004	0.078	-10000	0	-0.41	19	19
NCOA3	0.01	0.015	-10000	0	-0.33	1	1
NCOA1	0.01	0.018	-10000	0	-0.41	1	1
VDR/VDR/DNA	0.003	0.052	-10000	0	-0.33	13	13
RARG	0.012	0.001	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.015	0.001	-10000	0	-10000	0	0
MAPK3	0.012	0.001	-10000	0	-10000	0	0
MAPK1	0.011	0	-10000	0	-10000	0	0
MAPK8	0.007	0.044	-10000	0	-0.41	6	6
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.012	0.12	-10000	0	-0.38	44	44
RARA	-0.005	0.073	-10000	0	-0.22	47	47
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.01	0.071	-10000	0	-0.22	36	36
PRKCA	-0.015	0.11	-10000	0	-0.41	36	36
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.012	0.14	-10000	0	-0.42	45	45
RXRG	-0.052	0.13	-10000	0	-0.3	104	104
RXRA	0.002	0.068	-10000	0	-0.2	47	47
RXRB	-0.013	0.087	-10000	0	-0.28	42	42
VDR/Vit D3/DNA	0.003	0.036	-10000	0	-0.23	13	13
RBP1	-0.006	0.083	-10000	0	-0.41	22	22
CRBP1/9-cic-RA	-0.004	0.059	-10000	0	-0.29	22	22
RARB	0.004	0.06	-10000	0	-0.41	11	11
PRKCG	-0.035	0.12	-10000	0	-0.34	74	74
MNAT1	0.011	0	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.003	0.14	-10000	0	-0.42	44	44
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.003	0.11	-10000	0	-0.33	45	45
proteasomal ubiquitin-dependent protein catabolic process	0.013	0.069	-10000	0	-0.26	15	15
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.012	0.14	-10000	0	-0.42	45	45
positive regulation of DNA binding	-0.02	0.062	-10000	0	-0.22	39	39
NRIP1	-0.013	0.15	-10000	0	-0.78	10	10
RXRs/RARs	-0.017	0.14	-10000	0	-0.41	47	47
RXRs/RXRs/DNA/9cRA	-0.018	0.12	-10000	0	-0.4	44	44
PRKACA	0.011	0	-10000	0	-10000	0	0
CDK7	0.011	0	-10000	0	-10000	0	0
TFIIH	0.022	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.011	0.039	-10000	0	-0.33	2	2
CCNH	0.011	0	-10000	0	-10000	0	0
CREBBP	0.009	0.026	-10000	0	-0.41	2	2
RAR gamma2/9cRA	0	0	-10000	0	-10000	0	0

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.012	0.004	-10000	0	-10000	0	0
HSPA8	0.011	0.001	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.029	0.088	0.15	3	-0.25	65	68
AKT1	0.013	0.002	-10000	0	-10000	0	0
GSC	-0.029	0.077	-10000	0	-10000	0	0
NKX2-5	-0.05	0.12	-10000	0	-0.34	83	83
muscle cell differentiation	0.044	0.098	0.35	25	-10000	0	25
SMAD2-3/SMAD4/SP1	0.038	0.051	-10000	0	-0.26	3	3
SMAD4	0.007	0.035	-10000	0	-0.42	1	1
CBFB	0.011	0	-10000	0	-10000	0	0
SAP18	0.011	0	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.016	0.044	-10000	0	-0.2	18	18
SMAD3/SMAD4/VDR	0.005	0.041	-10000	0	-0.22	4	4
MYC	0.001	0.057	-10000	0	-0.41	10	10
CDKN2B	0.025	0.031	-10000	0	-10000	0	0
AP1	-0.025	0.12	-10000	0	-0.47	12	12
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.045	0.02	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.011	0.045	-10000	0	-0.34	3	3
SP3	0.013	0	-10000	0	-10000	0	0
CREB1	0.011	0	-10000	0	-10000	0	0
FOXH1	-0.079	0.15	-10000	0	-0.34	132	132
SMAD3/SMAD4/GR	-0.037	0.097	-10000	0	-0.25	82	82
GATA3	-0.004	0.072	-10000	0	-0.35	20	20
SKI/SIN3/HDAC complex/NCoR1	0.036	0.013	-10000	0	-10000	0	0
MEF2C/TIF2	-0.07	0.18	-10000	0	-0.41	85	85
endothelial cell migration	-0.015	0.11	1.2	4	-10000	0	4
MAX	0.01	0.004	-10000	0	-10000	0	0
RBBP7	0.011	0	-10000	0	-10000	0	0
RBBP4	0.009	0.031	-10000	0	-0.41	3	3
RUNX2	0.001	0.057	-10000	0	-0.34	15	15
RUNX3	0.002	0.054	-10000	0	-0.33	14	14
RUNX1	0.011	0	-10000	0	-10000	0	0
CTBP1	0.011	0	-10000	0	-10000	0	0
NR3C1	-0.052	0.15	-10000	0	-0.41	79	79
VDR	0.003	0.052	-10000	0	-0.33	13	13
CDKN1A	0.054	0.066	-10000	0	-1.2	1	1
KAT2B	0.004	0.054	-10000	0	-0.41	9	9
SMAD2/SMAD2/SMAD4/FOXH1	-0.036	0.1	-10000	0	-0.25	46	46
DCP1A	0.011	0	-10000	0	-10000	0	0
SKI	0.011	0	-10000	0	-10000	0	0
SERPINE1	0.015	0.12	-10000	0	-1.3	4	4
SMAD3/SMAD4/ATF2	0.011	0.048	-10000	0	-0.3	7	7
SMAD3/SMAD4/ATF3	-0.01	0.09	-10000	0	-0.27	52	52
SAP30	0.011	0	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.026	0.019	-10000	0	-0.22	2	2
JUN	-0.025	0.12	-10000	0	-0.48	11	11
SMAD3/SMAD4/IRF7	0.006	0.055	-10000	0	-0.28	9	9
TFE3	0.016	0.005	-10000	0	-10000	0	0
COL1A2	0.008	0.086	-10000	0	-0.79	5	5
mesenchymal cell differentiation	-0.006	0.059	0.27	16	-10000	0	16
DLX1	-0.031	0.11	-10000	0	-0.33	61	61
TCF3	0.011	0	-10000	0	-10000	0	0
FOS	-0.11	0.2	-10000	0	-0.41	165	165
SMAD3/SMAD4/Max	0.001	0.036	-10000	0	-0.27	4	4
Cbp/p300/SNIP1	0.023	0.016	-10000	0	-0.22	2	2
ZBTB17	0.009	0.002	-10000	0	-10000	0	0
LAMC1	0.033	0.036	-10000	0	-0.26	2	2
TGIF2/HDAC complex/SMAD3/SMAD4	0.013	0.04	-10000	0	-0.27	4	4
IRF7	0.004	0.051	-10000	0	-0.35	10	10
ESR1	-0.038	0.13	-10000	0	-0.41	61	61
HNF4A	-0.04	0.12	-10000	0	-0.33	78	78
MEF2C	-0.073	0.18	-10000	0	-0.43	80	80
SMAD2-3/SMAD4	0.017	0.048	-10000	0	-0.28	4	4
Cbp/p300/Src-1	0.023	0.02	-10000	0	-0.22	3	3
IGHV3OR16-13	-0.001	0.008	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.011	0	-10000	0	-10000	0	0
CREBBP	0.01	0.026	-10000	0	-0.41	2	2
SKIL	0.011	0	-10000	0	-10000	0	0
HDAC1	0.011	0	-10000	0	-10000	0	0
HDAC2	0.011	0	-10000	0	-10000	0	0
SNIP1	0.011	0.001	-10000	0	-10000	0	0
GCN5L2	0.001	0.004	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.03	0.044	-10000	0	-0.26	4	4
MSG1/HSC70	0.004	0.046	-10000	0	-0.23	20	20
SMAD2	0.008	0.018	-10000	0	-10000	0	0
SMAD3	0.009	0.047	-10000	0	-0.44	4	4
SMAD3/E2F4-5/DP1/p107/SMAD4	0.026	0.033	-10000	0	-0.22	4	4
SMAD2/SMAD2/SMAD4	0.002	0.042	-10000	0	-0.28	10	10
NCOR1	0.011	0	-10000	0	-10000	0	0
NCOA2	-0.004	0.078	-10000	0	-0.41	19	19
NCOA1	0.01	0.018	-10000	0	-0.41	1	1
MYOD/E2A	-0.011	0.068	-10000	0	-0.22	53	53
SMAD2-3/SMAD4/SP1/MIZ-1	0.044	0.049	-10000	0	-0.25	2	2
IFNB1	0.013	0.063	-10000	0	-0.31	13	13
SMAD3/SMAD4/MEF2C	-0.065	0.17	-10000	0	-0.44	69	69
CITED1	-0.002	0.067	-10000	0	-0.34	20	20
SMAD2-3/SMAD4/ARC105	0.024	0.044	-10000	0	-0.28	2	2
RBL1	0.011	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.041	0.037	-10000	0	-0.34	2	2
RUNX1-3/PEBPB2	0.017	0.031	-10000	0	-0.17	14	14
SMAD7	0	0.13	-10000	0	-0.48	12	12
MYC/MIZ-1	0.007	0.04	-10000	0	-0.28	10	10
SMAD3/SMAD4	0.012	0.055	-10000	0	-0.4	4	4
IL10	0.008	0.092	-10000	0	-0.28	37	37
PIASy/HDAC complex	0.01	0.003	-10000	0	-10000	0	0
PIAS3	0.011	0.002	-10000	0	-10000	0	0
CDK2	0.012	0.003	-10000	0	-10000	0	0
IL5	0.011	0.064	-10000	0	-0.32	4	4
CDK4	0.012	0.003	-10000	0	-10000	0	0
PIAS4	0.01	0.003	-10000	0	-10000	0	0
ATF3	-0.027	0.12	-10000	0	-0.41	48	48
SMAD3/SMAD4/SP1	0.033	0.048	-10000	0	-0.25	5	5
FOXG1	-0.16	0.17	-10000	0	-0.33	259	259
FOXO3	0.022	0.003	-10000	0	-10000	0	0
FOXO1	0.02	0.022	-10000	0	-0.28	3	3
FOXO4	0.021	0.018	-10000	0	-0.28	2	2
heart looping	-0.072	0.17	-10000	0	-0.42	80	80
CEBPB	0.012	0.002	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.011	0.081	-10000	0	-0.24	37	37
MYOD1	-0.029	0.1	-10000	0	-0.33	53	53
SMAD3/SMAD4/HNF4	-0.017	0.08	-10000	0	-0.23	30	30
SMAD3/SMAD4/GATA3	0	0.071	-10000	0	-0.28	12	12
SnoN/SIN3/HDAC complex/NCoR1	0.011	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.027	0.045	-10000	0	-0.24	2	2
SMAD3/SMAD4/SP1-3	0.041	0.046	-10000	0	-0.25	2	2
MED15	0.011	0	-10000	0	-10000	0	0
SP1	0.018	0.013	-10000	0	-10000	0	0
SIN3B	0.011	0	-10000	0	-10000	0	0
SIN3A	0.011	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.061	0.14	-10000	0	-0.34	65	65
ITGB5	0.043	0.036	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.037	0.013	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.031	0.11	-10000	0	-0.25	92	92
AR	-0.059	0.16	-10000	0	-0.41	90	90
negative regulation of cell growth	0.018	0.061	-10000	0	-0.3	5	5
SMAD3/SMAD4/MYOD	-0.01	0.07	-10000	0	-0.22	25	25
E2F5	0.011	0	-10000	0	-10000	0	0
E2F4	0.011	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.016	0.085	-10000	0	-0.25	13	13
SMAD2-3/SMAD4/FOXO1-3a-4	0.038	0.037	-10000	0	-0.35	2	2
TFDP1	0.011	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	-0.019	0.12	-10000	0	-0.47	12	12
SMAD3/SMAD4/RUNX2	0.007	0.059	-10000	0	-0.27	16	16
TGIF2	0.011	0	-10000	0	-10000	0	0
TGIF1	0.011	0	-10000	0	-10000	0	0
ATF2	0.009	0.031	-10000	0	-0.41	3	3

×

Signaling events mediated by PTP1B

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
PDGFRB	-0.006	0.083	-10000	0	-0.41	22	22
Jak2/Leptin Receptor	-0.097	0.14	-10000	0	-0.36	79	79
PTP1B/AKT1	0.017	0.04	-10000	0	-0.2	5	5
FYN	0.011	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	0.013	0.044	-10000	0	-0.23	5	5
EGFR	0.001	0.067	-10000	0	-0.41	14	14
EGF/EGFR	-0.016	0.049	-10000	0	-0.24	18	18
CSF1	0.003	0.057	-10000	0	-0.41	10	10
AKT1	0.011	0.001	-10000	0	-10000	0	0
INSR	0.011	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.012	0.089	-10000	0	-0.27	27	27
Insulin Receptor/Insulin	-0.008	0.022	-10000	0	-10000	0	0
HCK	0.007	0.039	-10000	0	-0.33	7	7
CRK	0.011	0	-10000	0	-10000	0	0
TYK2	0.018	0.041	-10000	0	-0.22	5	5
EGF	-0.004	0.07	-10000	0	-0.33	23	23
YES1	0.011	0	-10000	0	-10000	0	0
CAV1	-0.002	0.077	-10000	0	-0.29	14	14
TXN	0.011	0.002	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	0.005	0.078	-10000	0	-0.24	32	32
cell migration	-0.013	0.044	0.23	5	-10000	0	5
STAT3	0.011	0.001	-10000	0	-10000	0	0
PRLR	-0.072	0.17	-10000	0	-0.41	106	106
ITGA2B	0.005	0.047	-10000	0	-0.4	7	7
CSF1R	0.008	0.035	-10000	0	-0.39	4	4
Prolactin Receptor/Prolactin	-0.057	0.13	-10000	0	-0.29	123	123
FGR	0.002	0.062	-10000	0	-0.41	12	12
PTP1B/p130 Cas	0.018	0.041	-10000	0	-0.22	5	5
Crk/p130 Cas	0.024	0.04	-10000	0	-0.2	5	5
DOK1	0.015	0.06	-10000	0	-0.24	15	15
JAK2	-0.037	0.12	-10000	0	-0.32	50	50
Jak2/Leptin Receptor/Leptin	-0.014	0.051	-10000	0	-0.38	7	7
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
PTPN1	0.013	0.044	-10000	0	-0.23	5	5
LYN	0.011	0	-10000	0	-10000	0	0
CDH2	-0.052	0.15	-10000	0	-0.41	80	80
SRC	0.019	0.019	-10000	0	-10000	0	0
ITGB3	-0.067	0.16	-10000	0	-0.41	100	100
CAT1/PTP1B	0.017	0.072	-10000	0	-0.31	7	7
CAPN1	0.012	0.001	-10000	0	-10000	0	0
CSK	0.011	0	-10000	0	-10000	0	0
PI3K	-0.007	0.025	-10000	0	-0.23	2	2
mol:H2O2	0	0.001	-10000	0	-10000	0	0
STAT3 (dimer)	-0.012	0.047	-10000	0	-0.35	7	7
negative regulation of transcription	-0.036	0.12	-10000	0	-0.32	50	50
FCGR2A	0.01	0.015	-10000	0	-0.33	1	1
FER	0.011	0.002	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.043	0.12	-10000	0	-0.28	107	107
BLK	-0.015	0.087	-10000	0	-0.33	38	38
Insulin Receptor/Insulin/Shc	0.016	0.002	-10000	0	-10000	0	0
RHOA	0.012	0.001	-10000	0	-10000	0	0
LEPR	-0.12	0.19	-10000	0	-0.41	162	162
BCAR1	0.011	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.011	0	-10000	0	-10000	0	0
mol:NADPH	0.001	0.001	-10000	0	-10000	0	0
TRPV6	0.012	0.068	-10000	0	-0.33	7	7
PRL	-0.01	0.083	-10000	0	-0.39	24	24
SOCS3	0.005	0.075	-10000	0	-1.2	2	2
SPRY2	0.006	0.045	-10000	0	-0.41	6	6
Insulin Receptor/Insulin/IRS1	-0.009	0.075	-10000	0	-0.24	53	53
CSF1/CSF1R	0.019	0.057	-10000	0	-0.26	12	12
Ras protein signal transduction	0.007	0.014	-10000	0	-10000	0	0
IRS1	-0.03	0.12	-10000	0	-0.41	53	53
INS	0.001	0.003	-10000	0	-10000	0	0
LEP	0.005	0.026	-10000	0	-0.33	3	3
STAT5B	-0.003	0.065	-10000	0	-0.23	19	19
STAT5A	-0.003	0.064	-10000	0	-0.23	18	18
GRB2	0.011	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.01	0.063	-10000	0	-0.26	17	17
CSN2	-0.03	0.061	-10000	0	-10000	0	0
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
LAT	0.019	0.019	-10000	0	-10000	0	0
YBX1	0.017	0.018	-10000	0	-0.4	1	1
LCK	0.008	0.034	-10000	0	-0.35	5	5
SHC1	0.011	0	-10000	0	-10000	0	0
NOX4	0.007	0.039	-10000	0	-0.4	5	5

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.006	0.083	-9999	-0.41	22	22
alphaV beta3 Integrin	-0.038	0.12	-9999	-0.28	100	100
PTK2	-0.037	0.086	-9999	-0.38	23	23
positive regulation of JNK cascade	-0.014	0.058	-9999	-0.28	23	23
CDC42/GDP	0.019	0.088	-9999	-0.38	23	23
Rac1/GDP	0.02	0.087	-9999	-0.37	23	23
RAP1B	0.011	0	-9999	-10000	0	0
RAP1A	0.011	0	-9999	-10000	0	0
CTNNB1	0.011	0	-9999	-10000	0	0
CDC42/GTP	-0.017	0.07	-9999	-0.34	23	23
nectin-3/I-afadin	0.004	0.06	-9999	-0.28	23	23
RAPGEF1	0.012	0.095	-9999	-0.41	23	23
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.006	0.11	-9999	-0.47	23	23
PDGFB-D/PDGFRB	-0.006	0.083	-9999	-0.41	22	22
TLN1	0.002	0.076	-9999	-0.26	34	34
Rap1/GTP	-0.014	0.06	-9999	-0.3	23	23
IQGAP1	0.011	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.021	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.004	0.06	-9999	-0.28	23	23
PVR	0.011	0	-9999	-10000	0	0
Necl-5(dimer)	0.011	0	-9999	-10000	0	0
mol:GDP	0.014	0.1	-9999	-0.46	23	23
MLLT4	0.011	0	-9999	-10000	0	0
PIK3CA	0.01	0.018	-9999	-0.41	1	1
PI3K	0.013	0.069	-9999	-0.21	45	45
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.016	0.014	-9999	-0.22	2	2
positive regulation of lamellipodium assembly	-0.015	0.06	-9999	-0.3	23	23
PVRL1	0.01	0.021	-9999	-0.33	2	2
PVRL3	-0.007	0.085	-9999	-0.41	23	23
PVRL2	0.011	0	-9999	-10000	0	0
PIK3R1	0.007	0.04	-9999	-0.41	5	5
CDH1	0.009	0.026	-9999	-0.41	2	2
CLDN1	-0.044	0.14	-9999	-0.41	70	70
JAM-A/CLDN1	-0.011	0.091	-9999	-0.21	89	89
SRC	-0.001	0.12	-9999	-0.52	23	23
ITGB3	-0.067	0.16	-9999	-0.41	100	100
nectin-1(dimer)/I-afadin/I-afadin	0.016	0.014	-9999	-0.22	2	2
FARP2	0.01	0.1	-9999	-0.45	23	23
RAC1	0.011	0	-9999	-10000	0	0
CTNNA1	0.011	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.012	0.05	-9999	-0.23	23	23
nectin-1/I-afadin	0.016	0.014	-9999	-0.22	2	2
nectin-2/I-afadin	0.016	0	-9999	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0.015	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.011	0.054	-9999	-0.24	23	23
CDC42/GTP/IQGAP1/filamentous actin	0.015	0	-9999	-10000	0	0
F11R	0.01	0.018	-9999	-0.41	1	1
positive regulation of filopodium formation	-0.014	0.058	-9999	-0.28	23	23
alphaV/beta3 Integrin/Talin	-0.022	0.11	-9999	-0.31	40	40
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.016	0	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.016	0	-9999	-10000	0	0
PIP5K1C	-0.005	0.081	-9999	-0.23	56	56
VAV2	0.009	0.1	-9999	-0.46	23	23
RAP1/GDP	-0.016	0.071	-9999	-0.35	23	23
ITGAV	0.011	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.012	0.05	-9999	-0.23	23	23
nectin-3(dimer)/I-afadin/I-afadin	0.004	0.06	-9999	-0.28	23	23
Rac1/GTP	-0.018	0.073	-9999	-0.36	23	23
PTPRM	-0.013	0.089	-9999	-0.26	56	56
E-cadherin/beta catenin/alpha catenin	-0.001	0.012	-9999	-10000	0	0
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.011	0	-9999	-10000	0	0

×

Canonical Wnt signaling pathway

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
HDAC1	0.012	0.02	0.18	1	-10000	0	1
AES	0.012	0.017	0.16	1	-10000	0	1
FBXW11	0.011	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.015	0.018	-10000	0	-0.28	2	2
SMAD4	0.01	0.018	-10000	0	-0.41	1	1
DKK2	-0.016	0.1	-10000	0	-0.4	34	34
TLE1	0.011	0.025	0.16	1	-0.41	1	2
MACF1	0.011	0	-10000	0	-10000	0	0
CTNNB1	0.041	0.047	0.21	6	-10000	0	6
WIF1	-0.097	0.16	-10000	0	-0.35	160	160
beta catenin/RanBP3	0.02	0.093	0.36	35	-10000	0	35
KREMEN2	-0.021	0.1	-10000	0	-0.33	51	51
DKK1	-0.064	0.14	-10000	0	-0.34	115	115
beta catenin/beta TrCP1	0.045	0.044	0.2	6	-10000	0	6
FZD1	0.01	0.026	-10000	0	-0.41	2	2
AXIN2	-0.053	0.29	-10000	0	-1.3	27	27
AXIN1	0.011	0	-10000	0	-10000	0	0
RAN	0.011	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.014	0.023	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.05	0.055	0.22	1	-0.32	5	6
Axin1/APC/GSK3	0.018	0.031	0.17	4	-10000	0	4
Axin1/APC/GSK3/beta catenin/Macf1	0.044	0.026	-10000	0	-10000	0	0
HNF1A	0.006	0.045	0.16	1	-0.34	8	9
CTBP1	0.011	0.018	0.17	1	-10000	0	1
MYC	-0.017	0.18	-10000	0	-1.3	10	10
RANBP3	0.011	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.012	0.083	-10000	0	-0.2	80	80
NKD1	-0.02	0.1	-10000	0	-0.34	46	46
TCF4	-0.004	0.08	0.16	1	-0.4	20	21
TCF3	0.011	0.017	0.16	1	-10000	0	1
WNT1/LRP6/FZD1/Axin1	0.024	0.026	-10000	0	-0.2	2	2
Ran/GTP	0.008	0.002	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.02	0.11	0.41	35	-0.4	2	37
LEF1	0.007	0.044	0.16	1	-0.38	6	7
DVL1	0.03	0.019	-10000	0	-10000	0	0
CSNK2A1	0.011	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.047	0.076	-10000	0	-0.34	10	10
DKK1/LRP6/Kremen 2	-0.039	0.096	-10000	0	-0.18	159	159
LRP6	0.011	0	-10000	0	-10000	0	0
CSNK1A1	0.012	0.02	0.18	1	-10000	0	1
NLK	0.011	0.003	-10000	0	-10000	0	0
CCND1	0.002	0.058	-10000	0	-0.44	2	2
WNT1	0.004	0.041	-10000	0	-0.33	8	8
GSK3A	0.011	0	-10000	0	-10000	0	0
GSK3B	0.011	0	-10000	0	-10000	0	0
FRAT1	0.011	0	-10000	0	-10000	0	0
PPP2R5D	0.031	0.046	0.17	46	-10000	0	46
APC	0.028	0.024	-10000	0	-0.18	1	1
WNT1/LRP6/FZD1	0.038	0.058	0.2	33	-0.2	2	35
CREBBP	0.01	0.03	0.16	1	-0.39	2	3

×

Regulation of p38-alpha and p38-beta

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.015	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.011	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.033	0.11	-9999	-0.33	69	69
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.01	0.018	-9999	-0.41	1	1
RAC1-CDC42/GTP/PAK family	-0.007	0.068	-9999	-0.17	76	76
response to UV	0	0	-9999	-10000	0	0
YES1	0.011	0	-9999	-10000	0	0
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.011	0	-9999	-10000	0	0
FYN	0.011	0	-9999	-10000	0	0
MAP3K12	0.008	0.036	-9999	-0.41	4	4
FGR	0.002	0.062	-9999	-0.41	12	12
p38 alpha/TAB1	-0.003	0.016	-9999	-0.21	1	1
PRKG1	-0.18	0.21	-9999	-0.41	238	238
DUSP8	0.007	0.04	-9999	-0.41	5	5
PGK/cGMP/p38 alpha	-0.067	0.076	-9999	-0.18	77	77
apoptosis	-0.003	0.015	-9999	-0.2	1	1
RAL/GTP	0.015	0	-9999	-10000	0	0
LYN	0.011	0	-9999	-10000	0	0
DUSP1	-0.091	0.18	-9999	-0.41	130	130
PAK1	0.011	0	-9999	-10000	0	0
SRC	0.011	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.028	0	-9999	-10000	0	0
TRAF6	0.011	0	-9999	-10000	0	0
RAC1	0.011	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0.011	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0.015	0	-9999	-10000	0	0
MAPK11	0.032	0.036	-9999	-0.19	1	1
BLK	-0.015	0.087	-9999	-0.33	38	38
HCK	0.007	0.039	-9999	-0.33	7	7
MAP2K3	0.011	0	-9999	-10000	0	0
DUSP16	0.011	0	-9999	-10000	0	0
DUSP10	0.011	0	-9999	-10000	0	0
TRAF6/MEKK3	0.014	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.035	0.028	-9999	-0.23	1	1
positive regulation of innate immune response	0.039	0.039	-9999	-0.22	1	1
LCK	0.008	0.034	-9999	-0.35	5	5
p38alpha-beta/MKP7	0.043	0.038	-9999	-10000	0	0
p38alpha-beta/MKP5	0.043	0.038	-9999	-10000	0	0
PGK/cGMP	-0.12	0.15	-9999	-0.29	238	238
PAK2	0.011	0	-9999	-10000	0	0
p38alpha-beta/MKP1	0.018	0.074	-9999	-0.25	12	12
CDC42	0.011	0	-9999	-10000	0	0
RALB	0.011	0	-9999	-10000	0	0
RALA	0.011	0	-9999	-10000	0	0
PAK3	-0.052	0.14	-9999	-0.41	76	76

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.015	0.082	-10000	0	-0.2	85	85
MAPK9	0.007	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.004	0.034	-10000	0	-0.23	12	12
GNB1/GNG2	0.01	0.033	-10000	0	-0.23	10	10
GNB1	0.011	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.007	0	-10000	0	-10000	0	0
Gs family/GTP	-0.026	0.079	-10000	0	-0.22	79	79
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	0.009	0.021	0.06	79	-10000	0	79
GNAL	-0.051	0.15	-10000	0	-0.41	79	79
GNG2	0.003	0.056	-10000	0	-0.4	10	10
CRH	-0.006	0.049	-10000	0	-0.33	12	12
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.004	0.031	-10000	0	-0.28	6	6
MAPK11	0.006	0.018	-10000	0	-0.28	2	2

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.011	0	-9999	-10000	0	0
SPHK1	0.01	0.021	-9999	-0.33	2	2
GNAI2	0.011	0	-9999	-10000	0	0
mol:S1P	0.018	0.005	-9999	-10000	0	0
GNAO1	-0.1	0.18	-9999	-0.41	142	142
mol:Sphinganine-1-P	0.017	0.014	-9999	-0.22	2	2
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.032	0.004	-9999	-10000	0	0
GNAI3	0.011	0	-9999	-10000	0	0
G12/G13	0.016	0	-9999	-10000	0	0
S1PR3	-0.004	0.078	-9999	-0.41	19	19
S1PR2	0.011	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	0	0.003	-9999	-10000	0	0
S1PR5	0	0.063	-9999	-0.35	17	17
S1PR4	0.009	0.029	-9999	-0.38	3	3
GNAI1	0.005	0.051	-9999	-0.41	8	8
S1P/S1P5/G12	0.021	0.032	-9999	-0.19	4	4
S1P/S1P3/Gq	-0.008	0.11	-9999	-0.27	59	59
S1P/S1P4/Gi	-0.032	0.11	-9999	-0.2	154	154
GNAQ	0.009	0.026	-9999	-0.41	2	2
GNAZ	-0.001	0.069	-9999	-0.41	15	15
GNA14	-0.032	0.13	-9999	-0.41	55	55
GNA15	0.007	0.039	-9999	-0.33	7	7
GNA12	0.011	0	-9999	-10000	0	0
GNA13	0.011	0	-9999	-10000	0	0
GNA11	0.002	0.062	-9999	-0.41	12	12
ABCC1	0.011	0	-9999	-10000	0	0

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.01	0.042	-10000	0	-0.28	11	11
ATM	0.011	0	-10000	0	-10000	0	0
UBE2D3	0.011	0	-10000	0	-10000	0	0
PRKDC	0.011	0	-10000	0	-10000	0	0
ATR	0.011	0	-10000	0	-10000	0	0
UBE2L3	0.011	0	-10000	0	-10000	0	0
FANCD2	0.02	0.007	-10000	0	-10000	0	0
protein ubiquitination	-0.057	0.07	-10000	0	-0.25	11	11
XRCC5	0.011	0	-10000	0	-10000	0	0
XRCC6	0.011	0	-10000	0	-10000	0	0
M/R/N Complex	0.022	0	-10000	0	-10000	0	0
MRE11A	0.011	0	-10000	0	-10000	0	0
DNA-PK	0.022	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.019	0.029	-10000	0	-10000	0	0
FANCF	0.009	0.026	-10000	0	-0.41	2	2
BRCA1	0.011	0	-10000	0	-10000	0	0
CCNE1	-0.13	0.17	-10000	0	-0.33	217	217
CDK2/Cyclin E1	-0.078	0.12	-10000	0	-0.22	217	217
FANCG	0.011	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.01	0.042	-10000	0	-0.28	11	11
FANCE	0.011	0	-10000	0	-10000	0	0
FANCC	0.011	0	-10000	0	-10000	0	0
NBN	0.011	0	-10000	0	-10000	0	0
FANCA	-0.071	0.15	-10000	0	-0.33	129	129
DNA repair	-0.015	0.087	-10000	0	-0.31	7	7
BRCA1/BARD1/ubiquitin	0.01	0.042	-10000	0	-0.28	11	11
BARD1/DNA-PK	0.024	0.032	-10000	0	-0.2	11	11
FANCL	0.011	0	-10000	0	-10000	0	0
mRNA polyadenylation	-0.01	0.042	0.28	11	-10000	0	11
BRCA1/BARD1/CTIP/M/R/N Complex	0.028	0.031	-10000	0	-0.18	11	11
BRCA1/BACH1/BARD1/TopBP1	0.017	0.035	-10000	0	-0.23	11	11
BRCA1/BARD1/P53	0.023	0.034	-10000	0	-0.2	12	12
BARD1/CSTF1/BRCA1	0.017	0.035	-10000	0	-0.23	11	11
BRCA1/BACH1	0.011	0	-10000	0	-10000	0	0
BARD1	0.002	0.059	-10000	0	-0.41	11	11
PCNA	0.011	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	0.017	0.035	-10000	0	-0.23	11	11
BRCA1/BARD1/UbcH7	0.017	0.035	-10000	0	-0.23	11	11
BRCA1/BARD1/RAD51/PCNA	-0.029	0.089	-10000	0	-0.29	11	11
BARD1/DNA-PK/P53	0.028	0.031	-10000	0	-10000	0	0
BRCA1/BARD1/Ubiquitin	0.01	0.042	-10000	0	-0.28	11	11
BRCA1/BARD1/CTIP	0.023	0.032	-10000	0	-0.2	11	11
FA complex	0.013	0.036	-10000	0	-0.24	1	1
BARD1/EWS	0.01	0.042	-10000	0	-0.28	11	11
RBBP8	0.018	0	-10000	0	-10000	0	0
TP53	0.01	0.018	-10000	0	-0.41	1	1
TOPBP1	0.011	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.022	0.033	0.2	12	-10000	0	12
BRCA1/BARD1	-0.038	0.086	-10000	0	-0.25	11	11
CSTF1	0.011	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.002	0.042	-10000	0	-0.29	11	11
CDK2	0.011	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.09	0.16	-10000	0	-0.33	160	160
RAD50	0.011	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.01	0.042	-10000	0	-0.28	11	11
EWSR1	0.011	0	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.018	0.01	-9999	-0.22	1	1
BAD/BCL-XL/YWHAZ	0.027	0.008	-9999	-10000	0	0
CDKN1B	0.021	0.041	-9999	-0.22	1	1
CDKN1A	0.029	0.009	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
PRKDC	0.011	0	-9999	-10000	0	0
FOXO3	0.029	0.004	-9999	-10000	0	0
AKT1	0	0.002	-9999	-10000	0	0
BAD	0.011	0	-9999	-10000	0	0
AKT3	-0.095	0.14	-9999	-0.28	202	202
mol:GTP	0	0	-9999	-10000	0	0
FOXO4	0.029	0.013	-9999	-10000	0	0
AKT1/ASK1	0.027	0.015	-9999	-10000	0	0
BAD/YWHAZ	0.022	0	-9999	-10000	0	0
RICTOR	0.009	0.026	-9999	-0.41	2	2
RAF1	0.011	0	-9999	-10000	0	0
JNK cascade	-0.026	0.014	-9999	-10000	0	0
TSC1	0.029	0.009	-9999	-10000	0	0
YWHAZ	0.011	0	-9999	-10000	0	0
AKT1/RAF1	0.03	0.004	-9999	-10000	0	0
EP300	0.011	0	-9999	-10000	0	0
mol:GDP	0.024	0.004	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
TSC2	0.029	0.004	-9999	-10000	0	0
YWHAQ	0.011	0	-9999	-10000	0	0
TBC1D4	0.017	0.021	-9999	-0.22	4	4
MAP3K5	0.009	0.031	-9999	-0.41	3	3
MAPKAP1	0.011	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.011	0.015	-9999	-10000	0	0
YWHAH	0.011	0	-9999	-10000	0	0
AKT1S1	0.029	0.004	-9999	-10000	0	0
CASP9	0.029	0.004	-9999	-10000	0	0
YWHAB	0.011	0	-9999	-10000	0	0
p27Kip1/KPNA1	0.026	0.039	-9999	-10000	0	0
GBL	0	0	-9999	-10000	0	0
PDK1/Src/Hsp90	0.022	0	-9999	-10000	0	0
YWHAE	0.011	0	-9999	-10000	0	0
SRC	0.011	0	-9999	-10000	0	0
AKT2/p21CIP1	0.033	0.009	-9999	-10000	0	0
KIAA1303	0	0	-9999	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.015	0.002	-9999	-10000	0	0
CHUK	0.029	0.004	-9999	-10000	0	0
BAD/BCL-XL	0.04	0.007	-9999	-10000	0	0
mTORC2	0.013	0.014	-9999	-0.21	2	2
AKT2	0.014	0	-9999	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.022	0.018	-9999	-10000	0	0
PDPK1	0.011	0	-9999	-10000	0	0
MDM2	0.029	0.004	-9999	-10000	0	0
MAPKKK cascade	-0.029	0.004	-9999	-10000	0	0
MDM2/Cbp/p300	0.039	0.012	-9999	-10000	0	0
TSC1/TSC2	0.034	0.009	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.037	0.012	-9999	-10000	0	0
glucose import	-0.085	0.11	-9999	-0.2	263	263
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.025	0.004	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	-0.085	0.11	-9999	-0.2	263	263
GSK3A	0.029	0.004	-9999	-10000	0	0
FOXO1	0.028	0.015	-9999	-10000	0	0
GSK3B	0.029	0.004	-9999	-10000	0	0
SFN	-0.24	0.15	-9999	-0.33	395	395
G1/S transition of mitotic cell cycle	0.034	0.003	-9999	-10000	0	0
p27Kip1/14-3-3 family	-0.002	0.025	-9999	-10000	0	0
PRKACA	0.011	0	-9999	-10000	0	0
KPNA1	0.011	0	-9999	-10000	0	0
HSP90AA1	0.011	0	-9999	-10000	0	0
YWHAG	0.011	0	-9999	-10000	0	0
RHEB	0.011	0	-9999	-10000	0	0
CREBBP	0.009	0.026	-9999	-0.41	2	2

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.021	0.021	-9999	-0.17	6	6
SNTA1	0.011	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.021	0.021	-9999	-0.17	6	6
MAPK12	-0.01	0.073	-9999	-0.21	27	27
CCND1	0.003	0.033	-9999	-0.14	1	1
p38 gamma/SNTA1	-0.003	0.068	-9999	-0.19	27	27
MAP2K3	0.011	0	-9999	-10000	0	0
PKN1	0.011	0	-9999	-10000	0	0
G2/M transition checkpoint	-0.01	0.073	-9999	-0.21	27	27
MAP2K6	-0.017	0.08	-9999	-0.19	94	94
MAPT	0.002	0.062	-9999	-0.28	20	20
MAPK13	0.016	0.025	-9999	-0.22	6	6
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0	0.062	-9999	-0.28	26	26

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.13	0.12	-9999	-0.4	12	12
RAD9A	0.011	0	-9999	-10000	0	0
AP1	-0.081	0.14	-9999	-0.29	166	166
IFNAR2	0.007	0.019	-9999	-0.41	1	1
AKT1	-0.012	0.058	-9999	-0.18	24	24
ER alpha/Oestrogen	-0.027	0.093	-9999	-0.29	61	61
NFX1/SIN3/HDAC complex	0.032	0.016	-9999	-10000	0	0
EGF	-0.005	0.07	-9999	-0.34	23	23
SMG5	0.011	0	-9999	-10000	0	0
SMG6	0.011	0	-9999	-10000	0	0
SP3/HDAC2	0.012	0.009	-9999	-10000	0	0
TERT/c-Abl	-0.11	0.11	-9999	-0.41	9	9
SAP18	0.011	0.001	-9999	-10000	0	0
MRN complex	0.022	0	-9999	-10000	0	0
WT1	-0.3	0.18	-9999	-0.41	397	397
WRN	0.011	0	-9999	-10000	0	0
SP1	0.009	0.007	-9999	-10000	0	0
SP3	0.01	0.002	-9999	-10000	0	0
TERF2IP	0.011	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.1	0.091	-9999	-0.37	5	5
Mad/Max	0.012	0.009	-9999	-10000	0	0
TERT	-0.13	0.12	-9999	-0.43	8	8
CCND1	-0.11	0.11	-9999	-0.44	3	3
MAX	0.01	0.002	-9999	-10000	0	0
RBBP7	0.011	0.001	-9999	-10000	0	0
RBBP4	0.008	0.031	-9999	-0.41	3	3
TERF2	0.01	0	-9999	-10000	0	0
PTGES3	0.011	0	-9999	-10000	0	0
SIN3A	0.011	0.001	-9999	-10000	0	0
Telomerase/911	0.009	0.021	-9999	-10000	0	0
CDKN1B	-0.016	0.12	-9999	-0.5	23	23
RAD1	0.011	0	-9999	-10000	0	0
XRCC5	0.011	0	-9999	-10000	0	0
XRCC6	0.011	0	-9999	-10000	0	0
SAP30	0.011	0.001	-9999	-10000	0	0
TRF2/PARP2	0.016	0	-9999	-10000	0	0
UBE3A	0.01	0.002	-9999	-10000	0	0
JUN	0.005	0.048	-9999	-0.41	7	7
E6	-0.001	0.002	-9999	-10000	0	0
HPV-16 E6/E6AP	0.006	0.005	-9999	-10000	0	0
FOS	-0.12	0.19	-9999	-0.41	165	165
IFN-gamma/IRF1	-0.02	0.086	-9999	-0.22	82	82
PARP2	0.011	0	-9999	-10000	0	0
BLM	-0.027	0.11	-9999	-0.33	60	60
Telomerase	-0.012	0.036	-9999	-10000	0	0
IRF1	0.007	0.033	-9999	-10000	0	0
ESR1	-0.037	0.13	-9999	-0.41	61	61
KU/TER	0.016	0	-9999	-10000	0	0
ATM/TRF2	0.017	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.037	0.015	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.038	0.015	-9999	-10000	0	0
HDAC1	0.011	0.001	-9999	-10000	0	0
HDAC2	0.008	0.006	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.016	0.029	-9999	-0.28	5	5
ABL1	0.009	0.026	-9999	-0.41	2	2
MXD1	0.01	0.002	-9999	-10000	0	0
MRE11A	0.011	0	-9999	-10000	0	0
HUS1	0.011	0	-9999	-10000	0	0
RPS6KB1	0.011	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.096	0.096	-9999	-0.38	5	5
NR2F2	-0.008	0.091	-9999	-0.41	26	26
MAPK3	0.003	0.042	-9999	-0.22	18	18
MAPK1	0.003	0.042	-9999	-0.22	18	18
TGFB1/TGF beta receptor Type II	0.011	0.018	-9999	-0.41	1	1
NFKB1	0.01	0.018	-9999	-0.41	1	1
HNRNPC	0.011	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0	0	-9999	-10000	0	0
NBN	0.011	0	-9999	-10000	0	0
EGFR	0	0.066	-9999	-0.4	14	14
mol:Oestrogen	-0.001	0.001	-9999	-10000	0	0
EGF/EGFR	-0.006	0.067	-9999	-0.25	36	36
MYC	0.002	0.057	-9999	-0.41	10	10
IL2	-0.009	0.06	-9999	-0.33	18	18
KU	0.016	0	-9999	-10000	0	0
RAD50	0.011	0	-9999	-10000	0	0
HSP90AA1	0.011	0	-9999	-10000	0	0
TGFB1	0.011	0.018	-9999	-0.41	1	1
TRF2/BLM	-0.008	0.067	-9999	-0.2	60	60
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.11	0.11	-9999	-0.39	7	7
SP1/HDAC2	0.014	0.01	-9999	-10000	0	0
PINX1	0.011	0	-9999	-10000	0	0
Telomerase/EST1A	-0.1	0.091	-9999	-0.37	5	5
Smad3/Myc	0.015	0.043	-9999	-0.24	14	14
911 complex	0.022	0	-9999	-10000	0	0
IFNG	-0.032	0.11	-9999	-0.32	59	59
Telomerase/PinX1	-0.1	0.091	-9999	-0.37	5	5
Telomerase/AKT1/mTOR/p70S6K	-0.014	0.041	-9999	-10000	0	0
SIN3B	0.011	0.001	-9999	-10000	0	0
YWHAE	0.011	0	-9999	-10000	0	0
Telomerase/EST1B	-0.1	0.091	-9999	-0.36	6	6
response to DNA damage stimulus	0.003	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0.032	0	-9999	-10000	0	0
TRF2/WRN	0.016	0	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.1	0.091	-9999	-0.36	6	6
E2F1	-0.056	0.13	-9999	-0.33	101	101
ZNFX1	0.011	0.001	-9999	-10000	0	0
PIF1	-0.075	0.15	-9999	-0.33	136	136
NCL	0.011	0	-9999	-10000	0	0
DKC1	0.011	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	0.023	0.076	-10000	0	-0.33	8	8
TBX21	0.004	0.25	-10000	0	-1	18	18
B2M	0.012	0.005	-10000	0	-10000	0	0
TYK2	0.014	0.016	-10000	0	-10000	0	0
IL12RB1	0.002	0.072	-10000	0	-0.37	18	18
GADD45B	0.038	0.17	-10000	0	-0.71	11	11
IL12RB2	-0.005	0.081	-10000	0	-0.33	30	30
GADD45G	0.016	0.25	-10000	0	-0.97	23	23
natural killer cell activation	0.003	0.016	-10000	0	-10000	0	0
RELB	0.011	0	-10000	0	-10000	0	0
RELA	0.011	0	-10000	0	-10000	0	0
IL18	0.009	0.045	-10000	0	-0.33	9	9
IL2RA	-0.003	0.067	-10000	0	-0.33	21	21
IFNG	-0.029	0.11	-10000	0	-0.33	59	59
STAT3 (dimer)	0.028	0.18	-10000	0	-0.65	19	19
HLA-DRB5	-0.005	0.067	-10000	0	-0.38	16	16
FASLG	0.009	0.23	-10000	0	-1	14	14
NF kappa B2 p52/RelB	-0.063	0.17	-10000	0	-0.74	21	21
CD4	0.006	0.017	-10000	0	-0.35	1	1
SOCS1	0.01	0.018	-10000	0	-0.41	1	1
EntrezGene:6955	-0.006	0.014	-10000	0	-10000	0	0
CD3D	-0.008	0.073	-10000	0	-0.37	21	21
CD3E	-0.002	0.064	-10000	0	-0.39	14	14
CD3G	0	0.047	-10000	0	-0.35	9	9
IL12Rbeta2/JAK2	0.005	0.073	-10000	0	-0.24	39	39
CCL3	0.013	0.22	-10000	0	-0.92	13	13
CCL4	0.01	0.24	-10000	0	-0.97	16	16
HLA-A	0.011	0.015	-10000	0	-0.33	1	1
IL18/IL18R	0.042	0.054	-10000	0	-0.22	16	16
NOS2	0.019	0.23	-10000	0	-0.98	16	16
IL12/IL12R/TYK2/JAK2/SPHK2	0.023	0.073	-10000	0	-0.3	8	8
IL1R1	0.004	0.25	-10000	0	-1.1	18	18
IL4	0.001	0.017	-10000	0	-10000	0	0
JAK2	0.007	0.057	-10000	0	-0.42	9	9
EntrezGene:6957	-0.005	0.012	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.002	0.12	-10000	0	-0.56	18	18
RAB7A	0.044	0.18	-10000	0	-0.64	14	14
lysosomal transport	0.045	0.17	-10000	0	-0.6	14	14
FOS	-0.3	0.56	-10000	0	-1.1	168	168
STAT4 (dimer)	0.041	0.2	-10000	0	-0.67	19	19
STAT5A (dimer)	-0.073	0.18	-10000	0	-0.73	25	25
GZMA	-0.003	0.26	-10000	0	-1.1	20	20
GZMB	0.003	0.23	-10000	0	-0.99	14	14
HLX	0.011	0	-10000	0	-10000	0	0
LCK	0.02	0.23	-10000	0	-0.82	21	21
TCR/CD3/MHC II/CD4	-0.042	0.12	-10000	0	-0.2	164	164
IL2/IL2R	0.008	0.062	-10000	0	-0.3	14	14
MAPK14	0.036	0.2	-10000	0	-0.68	23	23
CCR5	0.03	0.2	-10000	0	-0.94	11	11
IL1B	0.011	0.042	-10000	0	-0.44	4	4
STAT6	0.024	0.077	-10000	0	-0.35	3	3
STAT4	0.01	0.018	-10000	0	-0.41	1	1
STAT3	0.011	0	-10000	0	-10000	0	0
STAT1	0.01	0.015	-10000	0	-0.33	1	1
NFKB1	0.01	0.018	-10000	0	-0.41	1	1
NFKB2	0.011	0	-10000	0	-10000	0	0
IL12B	0.01	0.021	-10000	0	-0.31	1	1
CD8A	0.001	0.067	-10000	0	-0.39	15	15
CD8B	-0.01	0.087	-10000	0	-0.35	33	33
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.023	0.075	0.33	8	-10000	0	8
IL2RB	0.01	0.018	-10000	0	-0.41	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.041	0.19	-10000	0	-0.62	19	19
IL2RG	0.005	0.047	-10000	0	-0.36	9	9
IL12	0.014	0.05	-10000	0	-0.23	16	16
STAT5A	0.01	0.018	-10000	0	-0.41	1	1
CD247	0.006	0.031	-10000	0	-0.38	3	3
IL2	-0.007	0.06	-10000	0	-0.33	18	18
SPHK2	0.011	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.003	0.062	-10000	0	-0.35	15	15
IL12/IL12R/TYK2/JAK2	0.02	0.24	-10000	0	-0.85	22	22
MAP2K3	0.032	0.2	-10000	0	-0.66	24	24
RIPK2	0.011	0	-10000	0	-10000	0	0
MAP2K6	0.033	0.2	-10000	0	-0.67	23	23
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.004	0.028	-10000	0	-0.42	2	2
IL18RAP	0.01	0.045	-10000	0	-0.38	7	7
IL12Rbeta1/TYK2	0.012	0.056	-10000	0	-0.26	18	18
EOMES	-0.009	0.14	-10000	0	-1.2	7	7
STAT1 (dimer)	0.03	0.18	-10000	0	-0.66	17	17
T cell proliferation	0.038	0.16	-10000	0	-0.51	20	20
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.012	0.037	-10000	0	-0.41	4	4
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.039	0.13	0.24	1	-0.55	22	23
ATF2	0.039	0.19	-10000	0	-0.63	24	24

×

IL1-mediated signaling events

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
UBC13/UEV1A	-0.008	0.072	-10000	0	-0.28	35	35
PRKCZ	0.01	0.023	-10000	0	-0.37	2	2
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.011	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.003	0.023	-10000	0	-0.23	4	4
IRAK/TOLLIP	0.009	0.054	-10000	0	-0.2	35	35
IKBKB	0.011	0	-10000	0	-10000	0	0
IKBKG	0.011	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.015	0.086	-10000	0	-0.24	65	65
IL1A	-0.011	0.083	-10000	0	-0.33	34	34
IL1B	0.015	0.035	-10000	0	-0.33	5	5
IRAK/TRAF6/p62/Atypical PKCs	0.023	0.049	-10000	0	-0.34	1	1
IL1R2	-0.013	0.089	-10000	0	-0.34	37	37
IL1R1	0.004	0.054	-10000	0	-0.41	9	9
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.026	0.057	0.18	23	-0.26	10	33
TOLLIP	0.011	0	-10000	0	-10000	0	0
TICAM2	0.004	0.051	-10000	0	-0.41	8	8
MAP3K3	0.011	0	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.007	0	-10000	0	-10000	0	0
IKK complex/ELKS	0.04	0.043	-10000	0	-10000	0	0
JUN	0.001	0.07	-10000	0	-0.28	10	10
MAP3K7	0.011	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.028	0.049	-10000	0	-0.42	3	3
IL1 alpha/IL1R1/IL1RAP/MYD88	0.012	0.056	-10000	0	-0.23	11	11
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.017	0.053	-10000	0	-0.21	11	11
IL1 beta fragment/IL1R1/IL1RAP	0.02	0.044	-10000	0	-0.22	16	16
NFKB1	0.01	0.018	-10000	0	-0.41	1	1
MAPK8	-0.002	0.07	-10000	0	-0.29	8	8
IRAK1	0.002	0.06	-10000	0	-0.23	35	35
IL1RN/IL1R1	-0.022	0.091	-10000	0	-0.23	85	85
IRAK4	0.011	0	-10000	0	-10000	0	0
PRKCI	0.011	0	-10000	0	-10000	0	0
TRAF6	0.011	0	-10000	0	-10000	0	0
PI3K	0.013	0.031	-10000	0	-0.28	6	6
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.026	0.04	-10000	0	-0.21	12	12
CHUK	0.011	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.02	0.044	-10000	0	-0.22	16	16
IL1 beta/IL1R2	0.005	0.058	-10000	0	-0.25	9	9
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.011	0.041	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.007	0.039	-10000	0	-0.38	3	3
IRAK3	-0.008	0.087	-10000	0	-0.41	24	24
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.027	0.048	-10000	0	-0.36	3	3
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.02	0.04	-10000	0	-0.22	11	11
IL1 alpha/IL1R1/IL1RAP	0.004	0.062	-10000	0	-0.2	44	44
RELA	0.011	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.011	0	-10000	0	-10000	0	0
MYD88	0.011	0	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0.015	0.051	-10000	0	-0.18	35	35
IL1RAP	0.009	0.031	-10000	0	-0.41	3	3
UBE2N	0.011	0	-10000	0	-10000	0	0
IRAK/TRAF6	-0.015	0.048	-10000	0	-0.3	6	6
CASP1	0.009	0.026	-10000	0	-0.41	2	2
IL1RN/IL1R2	-0.034	0.1	-10000	0	-0.24	106	106
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.026	0.042	-10000	0	-0.38	2	2
TMEM189-UBE2V1	-0.023	0.1	-10000	0	-0.41	35	35
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.017	0.058	-10000	0	-0.34	9	9
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
IL1RN	-0.038	0.12	-10000	0	-0.33	78	78
TRAF6/TAK1/TAB1/TAB2	-0.011	0.044	-10000	0	-0.18	35	35
MAP2K6	-0.006	0.071	-10000	0	-0.31	7	7

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.012	0.067	-10000	0	-0.35	15	15
FYN	0.033	0.1	-10000	0	-0.44	16	16
LAT/GRAP2/SLP76	-0.012	0.082	-10000	0	-0.39	18	18
IKBKB	0.011	0	-10000	0	-10000	0	0
AKT1	0.038	0.077	-10000	0	-0.32	17	17
B2M	0.012	0.002	-10000	0	-10000	0	0
IKBKG	-0.004	0.018	-10000	0	-0.12	8	8
MAP3K8	0.009	0.031	-10000	0	-0.41	3	3
mol:Ca2+	-0.006	0.017	-10000	0	-0.081	19	19
integrin-mediated signaling pathway	0.015	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.037	0.1	-10000	0	-0.44	18	18
TRPV6	-0.044	0.13	-10000	0	-0.4	59	59
CD28	0.01	0.021	-10000	0	-0.33	2	2
SHC1	0.033	0.096	-10000	0	-0.43	16	16
receptor internalization	0.027	0.089	-10000	0	-0.43	15	15
PRF1	0.021	0.13	-10000	0	-0.99	7	7
KRAS	0.01	0.015	-10000	0	-0.33	1	1
GRB2	0.011	0	-10000	0	-10000	0	0
COT/AKT1	0.039	0.064	-10000	0	-0.27	15	15
LAT	0.033	0.096	-10000	0	-0.43	16	16
EntrezGene:6955	0.001	0.002	-10000	0	-10000	0	0
CD3D	-0.002	0.072	-10000	0	-0.36	21	21
CD3E	0.002	0.064	-10000	0	-0.39	14	14
CD3G	0.006	0.047	-10000	0	-0.35	9	9
RASGRP2	-0.011	0.058	-10000	0	-0.16	73	73
RASGRP1	0.04	0.085	-10000	0	-0.36	16	16
HLA-A	0.012	0.015	-10000	0	-0.33	1	1
RASSF5	0.011	0	-10000	0	-10000	0	0
RAP1A/GTP/RAPL	0.015	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.025	0.035	-10000	0	-0.11	12	12
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.008	0.032	-10000	0	-0.18	13	13
PRKCA	-0.006	0.046	-10000	0	-0.21	16	16
GRAP2	-0.002	0.073	-10000	0	-0.41	17	17
mol:IP3	0.003	0.081	0.18	51	-0.32	14	65
EntrezGene:6957	0.001	0.002	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	0.019	0.083	-10000	0	-0.41	14	14
ORAI1	0.027	0.074	0.24	59	-10000	0	59
CSK	0.031	0.098	-10000	0	-0.42	17	17
B7 family/CD28	0.036	0.097	-10000	0	-0.43	16	16
CHUK	0.011	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	0.027	0.11	-10000	0	-0.47	17	17
PTPN6	0.03	0.097	-10000	0	-0.43	16	16
VAV1	0.031	0.1	-10000	0	-0.45	16	16
Monovalent TCR/CD3	0.012	0.063	-10000	0	-0.29	19	19
CBL	0.011	0	-10000	0	-10000	0	0
LCK	0.03	0.1	-10000	0	-0.46	16	16
PAG1	0.031	0.1	-10000	0	-0.42	18	18
RAP1A	0.011	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	0.027	0.11	-10000	0	-0.48	16	16
CD80	-0.008	0.078	-10000	0	-0.33	30	30
CD86	0.01	0.021	-10000	0	-0.34	2	2
PDK1/CARD11/BCL10/MALT1	-0.01	0.039	-10000	0	-0.22	13	13
HRAS	0.011	0	-10000	0	-10000	0	0
GO:0035030	0.03	0.085	-10000	0	-0.37	16	16
CD8A	0.001	0.067	-10000	0	-0.39	15	15
CD8B	-0.01	0.087	-10000	0	-0.35	33	33
PTPRC	0.003	0.059	-10000	0	-0.4	11	11
PDK1/PKC theta	0.04	0.096	-10000	0	-0.38	19	19
CSK/PAG1	0.033	0.098	-10000	0	-0.41	18	18
SOS1	0.011	0	-10000	0	-10000	0	0
peptide-MHC class I	0.018	0.011	-10000	0	-0.22	1	1
GRAP2/SLP76	-0.014	0.094	-10000	0	-0.44	19	19
STIM1	0.013	0.036	-10000	0	-10000	0	0
RAS family/GTP	0.039	0.036	-10000	0	-0.16	6	6
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	0.027	0.093	-10000	0	-0.45	15	15
mol:DAG	-0.006	0.059	-10000	0	-0.29	15	15
RAP1A/GDP	0.012	0.015	-10000	0	-0.055	7	7
PLCG1	0.011	0	-10000	0	-10000	0	0
CD247	0.01	0.03	-10000	0	-0.39	3	3
cytotoxic T cell degranulation	0.022	0.13	-10000	0	-0.92	7	7
RAP1A/GTP	-0.008	0.019	-10000	0	-0.057	73	73
mol:PI-3-4-5-P3	0.038	0.089	-10000	0	-0.37	18	18
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.001	0.096	0.19	49	-0.41	14	63
NRAS	0.011	0	-10000	0	-10000	0	0
ZAP70	-0.001	0.063	-10000	0	-0.34	18	18
GRB2/SOS1	0.016	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.012	0.08	-10000	0	-0.4	16	16
MALT1	0.011	0	-10000	0	-10000	0	0
TRAF6	0.011	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.004	0.08	-10000	0	-0.26	44	44
CARD11	0.002	0.057	-10000	0	-0.35	14	14
PRKCB	-0.008	0.057	-10000	0	-0.27	20	20
PRKCE	-0.003	0.042	-10000	0	-0.21	14	14
PRKCQ	0.034	0.11	-10000	0	-0.42	20	20
LCP2	0.01	0.015	-10000	0	-0.33	1	1
BCL10	0.011	0	-10000	0	-10000	0	0
regulation of survival gene product expression	0.037	0.068	-10000	0	-0.28	16	16
IKK complex	0.03	0.037	-10000	0	-0.097	15	15
RAS family/GDP	-0.001	0.005	-10000	0	-10000	0	0
MAP3K14	0.039	0.051	-10000	0	-0.21	13	13
PDPK1	0.04	0.074	-10000	0	-0.31	16	16
TCR/CD3/MHC I/CD8/Fyn	0.021	0.12	-10000	0	-0.48	21	21

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	0.005	0.047	-10000	0	-0.22	22	22
cell-cell adhesion	0.03	0.063	0.3	9	-10000	0	9
Ephrin B/EPHB2/RasGAP	0.008	0.069	-10000	0	-0.38	1	1
ITSN1	0.011	0	-10000	0	-10000	0	0
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
SHC1	0.011	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	0.006	0.044	-10000	0	-0.21	21	21
Ephrin B1/EPHB1	-0.01	0.074	-10000	0	-0.23	54	54
HRAS/GDP	-0.03	0.067	-10000	0	-0.3	10	10
Ephrin B/EPHB1/GRB7	-0.02	0.098	-10000	0	-0.36	12	12
Endophilin/SYNJ1	0.008	0.062	-10000	0	-0.36	1	1
KRAS	0.01	0.015	-10000	0	-0.33	1	1
Ephrin B/EPHB1/Src	-0.01	0.092	-10000	0	-0.38	8	8
endothelial cell migration	-0.003	0.025	-10000	0	-0.18	10	10
GRB2	0.011	0	-10000	0	-10000	0	0
GRB7	-0.01	0.083	-10000	0	-0.34	33	33
PAK1	0.012	0.067	-10000	0	-0.36	3	3
HRAS	0.011	0	-10000	0	-10000	0	0
RRAS	0.009	0.062	-10000	0	-0.36	1	1
DNM1	0.006	0.044	-10000	0	-0.41	6	6
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.01	0.086	-10000	0	-0.36	8	8
lamellipodium assembly	-0.03	0.063	-10000	0	-0.3	9	9
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.009	0.089	-10000	0	-0.21	54	54
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
EPHB2	0.009	0.025	-10000	0	-0.33	3	3
EPHB3	-0.003	0.071	-10000	0	-0.35	21	21
EPHB1	-0.03	0.12	-10000	0	-0.41	53	53
EPHB4	0.01	0.018	-10000	0	-0.41	1	1
mol:GDP	-0.001	0.084	-10000	0	-0.32	10	10
Ephrin B/EPHB2	0.004	0.066	-10000	0	-0.19	54	54
Ephrin B/EPHB3	-0.002	0.082	-10000	0	-0.22	57	57
JNK cascade	0.008	0.065	-10000	0	-0.37	1	1
Ephrin B/EPHB1	-0.016	0.091	-10000	0	-0.2	98	98
RAP1/GDP	0.01	0.076	-10000	0	-0.27	10	10
EFNB2	0.009	0.031	-10000	0	-0.41	3	3
EFNB3	-0.029	0.12	-10000	0	-0.41	51	51
EFNB1	0.01	0.018	-10000	0	-0.41	1	1
Ephrin B2/EPHB1-2	-0.003	0.069	-10000	0	-0.2	54	54
RAP1B	0.011	0	-10000	0	-10000	0	0
RAP1A	0.011	0	-10000	0	-10000	0	0
CDC42/GTP	-0.034	0.073	-10000	0	-0.35	9	9
Rap1/GTP	-0.029	0.062	-10000	0	-0.3	9	9
axon guidance	0.005	0.047	-10000	0	-0.22	22	22
MAPK3	0.004	0.08	-10000	0	-0.32	8	8
MAPK1	0.004	0.08	-10000	0	-0.32	8	8
Rac1/GDP	0.006	0.079	-10000	0	-0.29	10	10
actin cytoskeleton reorganization	-0.023	0.05	-10000	0	-0.25	9	9
CDC42/GDP	0.006	0.079	-10000	0	-0.29	10	10
PI3K	0.022	0.029	-10000	0	-0.18	10	10
EFNA5	-0.004	0.076	-10000	0	-0.4	19	19
Ephrin B2/EPHB4	0.013	0.021	-10000	0	-0.23	4	4
Ephrin B/EPHB2/Intersectin/N-WASP	0.007	0.068	-10000	0	-0.19	54	54
CDC42	0.011	0	-10000	0	-10000	0	0
RAS family/GTP	-0.028	0.061	-10000	0	-0.3	9	9
PTK2	0.006	0.018	-10000	0	-10000	0	0
MAP4K4	0.008	0.065	-10000	0	-0.38	1	1
SRC	0.011	0	-10000	0	-10000	0	0
KALRN	0.007	0.04	-10000	0	-0.41	5	5
Intersectin/N-WASP	0.016	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.018	0.08	-10000	0	-0.28	11	11
MAP2K1	-0.002	0.084	-10000	0	-0.34	8	8
WASL	0.011	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	0.004	0.071	-10000	0	-0.2	53	53
cell migration	-0.004	0.099	-10000	0	-0.34	11	11
NRAS	0.011	0	-10000	0	-10000	0	0
SYNJ1	0.009	0.062	-10000	0	-0.36	1	1
PXN	0.011	0	-10000	0	-10000	0	0
TF	0.005	0.072	-10000	0	-0.32	5	5
HRAS/GTP	-0.032	0.068	-10000	0	-0.33	9	9
Ephrin B1/EPHB1-2	-0.002	0.068	-10000	0	-0.2	57	57
cell adhesion mediated by integrin	0.017	0.066	0.2	54	-10000	0	54
RAC1	0.011	0	-10000	0	-10000	0	0
mol:GTP	-0.007	0.087	-10000	0	-0.35	9	9
RAC1-CDC42/GTP	-0.034	0.072	-10000	0	-0.3	19	19
RASA1	0.007	0.04	-10000	0	-0.41	5	5
RAC1-CDC42/GDP	0.01	0.076	-10000	0	-0.29	8	8
ruffle organization	0.009	0.081	-10000	0	-0.31	9	9
NCK1	0.009	0.026	-10000	0	-0.41	2	2
receptor internalization	0.012	0.067	-10000	0	-0.34	5	5
Ephrin B/EPHB2/KALRN	0.008	0.071	-10000	0	-0.38	3	3
ROCK1	0.012	0.04	-10000	0	-0.24	6	6
RAS family/GDP	-0.023	0.05	-10000	0	-0.24	9	9
Rac1/GTP	-0.031	0.066	-10000	0	-0.32	9	9
Ephrin B/EPHB1/Src/Paxillin	-0.013	0.095	-10000	0	-0.21	98	98

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	-0.13	0.17	-9999	-0.33	217	217
mol:Halofuginone	0.004	0	-9999	-10000	0	0
ITGA1	0.009	0.031	-9999	-0.41	3	3
CDKN1A	0.012	0.04	-9999	-0.36	1	1
PRL-3/alpha Tubulin	0.016	0	-9999	-10000	0	0
mol:Ca2+	-0.043	0.1	-9999	-0.29	80	80
AGT	-0.05	0.15	-9999	-0.4	80	80
CCNA2	-0.028	0.098	-9999	-0.33	19	19
TUBA1B	0.011	0	-9999	-10000	0	0
EGR1	-0.019	0.099	-9999	-0.28	70	70
CDK2/Cyclin E1	-0.041	0.088	-9999	-0.46	1	1
MAPK3	0.018	0	-9999	-10000	0	0
PRL-2 /Rab GGTase beta	0.016	0	-9999	-10000	0	0
MAPK1	0.018	0	-9999	-10000	0	0
PTP4A1	0	0.075	-9999	-10000	0	0
PTP4A3	0.011	0	-9999	-10000	0	0
PTP4A2	0.011	0	-9999	-10000	0	0
ITGB1	0.018	0	-9999	-10000	0	0
SRC	0.011	0	-9999	-10000	0	0
RAC1	0.013	0.036	-9999	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0.016	0	-9999	-10000	0	0
PRL-1/ATF-5	0.005	0.071	-9999	-0.33	1	1
RABGGTA	0.011	0	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
RHOC	0.013	0.036	-9999	-10000	0	0
RHOA	0.013	0.036	-9999	-10000	0	0
cell motility	0.016	0.039	-9999	-10000	0	0
PRL-1/alpha Tubulin	0.006	0.069	-9999	-10000	0	0
PRL-3/alpha1 Integrin	0.015	0.022	-9999	-0.28	3	3
ROCK1	0.016	0.039	-9999	-10000	0	0
RABGGTB	0.011	0	-9999	-10000	0	0
CDK2	0.011	0	-9999	-10000	0	0
mitosis	0	0.074	-9999	-10000	0	0
ATF5	0.008	0.029	-9999	-0.33	4	4

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.014	0.051	-10000	0	-0.17	11	11
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	0.011	0	-10000	0	-10000	0	0
STAT1 (dimer)/Cbp/p300	0.037	0.047	-10000	0	-0.21	1	1
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.015	0.037	-10000	0	-0.23	11	11
antigen processing and presentation of peptide antigen via MHC class I	-0.031	0.042	-10000	0	-0.26	4	4
CaM/Ca2+	-0.013	0.036	-10000	0	-10000	0	0
RAP1A	0.011	0	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	0.018	0.049	-10000	0	-0.24	1	1
AKT1	0.024	0.049	-10000	0	-0.28	2	2
MAP2K1	0.024	0.046	-10000	0	-10000	0	0
MAP3K11	0.017	0.048	-10000	0	-10000	0	0
IFNGR1	0.011	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.19	0.16	-10000	0	-0.33	301	301
Rap1/GTP	-0.009	0.023	-10000	0	-10000	0	0
CRKL/C3G	0.016	0	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.013	0.055	-10000	0	-10000	0	0
CEBPB	0.048	0.048	-10000	0	-0.38	2	2
STAT3	0.011	0	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.017	0.067	-10000	0	-1	1	1
STAT1	0.018	0.049	-10000	0	-0.24	1	1
CALM1	0.011	0	-10000	0	-10000	0	0
IFN-gamma (dimer)	-0.027	0.1	-10000	0	-0.32	59	59
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
STAT1 (dimer)/PIAS1	0.023	0.047	-10000	0	-0.23	1	1
CEBPB/PTGES2/Cbp/p300	-0.003	0.018	-10000	0	-0.24	2	2
mol:Ca2+	0.012	0.05	-10000	0	-0.17	11	11
MAPK3	0.033	0.042	-10000	0	-10000	0	0
STAT1 (dimer)	-0.039	0.057	-10000	0	-0.36	4	4
MAPK1	0.033	0.042	-10000	0	-10000	0	0
JAK2	0.004	0.054	-10000	0	-0.41	9	9
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
JAK1	0.01	0.026	-10000	0	-0.41	2	2
CAMK2D	0.009	0.026	-10000	0	-0.41	2	2
DAPK1	0.046	0.049	-10000	0	-0.57	2	2
SMAD7	0.001	0.041	-10000	0	-0.29	2	2
CBL/CRKL/C3G	0.027	0.044	-10000	0	-10000	0	0
PI3K	-0.014	0.039	-10000	0	-0.3	2	2
IFNG	-0.027	0.1	-10000	0	-0.32	59	59
apoptosis	0.027	0.04	-10000	0	-0.43	2	2
CAMK2G	0.011	0	-10000	0	-10000	0	0
STAT3 (dimer)	0.011	0	-10000	0	-10000	0	0
CAMK2A	-0.23	0.21	-10000	0	-0.41	301	301
CAMK2B	-0.046	0.13	-10000	0	-0.33	89	89
FRAP1	0.023	0.046	-10000	0	-0.27	2	2
PRKCD	0.025	0.05	-10000	0	-0.28	2	2
RAP1B	0.011	0	-10000	0	-10000	0	0
negative regulation of cell growth	-0.031	0.042	-10000	0	-0.26	4	4
PTPN2	0.011	0	-10000	0	-10000	0	0
EP300	0.011	0	-10000	0	-10000	0	0
IRF1	0.044	0.042	-10000	0	-0.25	1	1
STAT1 (dimer)/PIASy	0.02	0.047	0.18	1	-0.23	1	2
SOCS1	0.001	0.055	-10000	0	-1.3	1	1
mol:GDP	-0.011	0.029	-10000	0	-10000	0	0
CASP1	0.001	0.04	-10000	0	-0.21	3	3
PTGES2	0.01	0.018	-10000	0	-0.41	1	1
IRF9	0.04	0.019	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.014	0.038	-10000	0	-0.3	2	2
RAP1/GDP	-0.009	0.024	-10000	0	-10000	0	0
CBL	0.017	0.048	-10000	0	-10000	0	0
MAP3K1	0.018	0.048	-10000	0	-10000	0	0
PIAS1	0.011	0	-10000	0	-10000	0	0
PIAS4	0.011	0	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.031	0.042	-10000	0	-0.26	4	4
PTPN11	0.011	0.05	-10000	0	-0.17	11	11
CREBBP	0.01	0.026	-10000	0	-0.41	2	2
RAPGEF1	0.011	0	-10000	0	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.01	0.015	-10000	0	-0.33	1	1
NFATC1	0.034	0.05	-10000	0	-0.25	15	15
NFATC2	0.015	0.048	-10000	0	-0.21	8	8
NFATC3	0.018	0.016	-10000	0	-0.31	1	1
YWHAE	0.011	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.017	0.1	-10000	0	-0.36	27	27
Exportin 1/Ran/NUP214	0.021	0.006	-10000	0	-10000	0	0
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.032	0.08	-10000	0	-0.35	22	22
BCL2/BAX	-0.011	0.086	-10000	0	-0.28	50	50
CaM/Ca2+/Calcineurin A alpha-beta B1	0.008	0.004	-10000	0	-10000	0	0
CaM/Ca2+	0.008	0.004	-10000	0	-10000	0	0
BAX	0.011	0	-10000	0	-10000	0	0
MAPK14	0.011	0.003	-10000	0	-10000	0	0
BAD	0.011	0	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.011	0.099	-10000	0	-0.38	21	21
Calcineurin A alpha-beta B1/BCL2	-0.028	0.12	-10000	0	-0.41	50	50
FKBP8	0.011	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.01	0.098	0.38	21	-10000	0	21
KPNB1	0.011	0	-10000	0	-10000	0	0
KPNA2	-0.004	0.07	-10000	0	-0.33	24	24
XPO1	0.011	0	-10000	0	-10000	0	0
SFN	-0.24	0.15	-10000	0	-0.33	395	395
MAP3K8	0.008	0.031	-10000	0	-0.41	3	3
NFAT4/CK1 alpha	0.026	0.012	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	0.025	0.077	-10000	0	-0.23	36	36
CABIN1	-0.017	0.1	-10000	0	-0.36	27	27
CALM1	0.011	0.002	-10000	0	-10000	0	0
RAN	0.011	0	-10000	0	-10000	0	0
MAP3K1	0.011	0	-10000	0	-10000	0	0
CAMK4	0.003	0.051	-10000	0	-0.36	10	10
mol:Ca2+	0	0.004	-10000	0	-10000	0	0
MAPK3	0.011	0	-10000	0	-10000	0	0
YWHAH	0.011	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.014	0.022	-10000	0	-0.28	3	3
YWHAB	0.011	0	-10000	0	-10000	0	0
MAPK8	0.006	0.044	-10000	0	-0.41	6	6
MAPK9	0.011	0	-10000	0	-10000	0	0
YWHAG	0.011	0	-10000	0	-10000	0	0
FKBP1A	0.011	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.044	0.048	-10000	0	-0.27	1	1
PRKCH	0.009	0.031	-10000	0	-0.41	3	3
CABIN1/Cbp/p300	0.015	0.019	-10000	0	-0.28	2	2
CASP3	0.011	0.003	-10000	0	-10000	0	0
PIM1	0.011	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.008	0.002	-10000	0	-10000	0	0
apoptosis	-0.007	0.023	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.001	0.02	-10000	0	-10000	0	0
PRKCB	-0.014	0.099	-10000	0	-0.41	32	32
PRKCE	0.011	0	-10000	0	-10000	0	0
JNK2/NFAT4	0.022	0.014	-10000	0	-0.28	1	1
BAD/BCL-XL	0.016	0.01	-10000	0	-0.22	1	1
PRKCD	0.011	0	-10000	0	-10000	0	0
NUP214	0.011	0	-10000	0	-10000	0	0
PRKCZ	0.009	0.023	-10000	0	-0.37	2	2
PRKCA	-0.017	0.1	-10000	0	-0.41	36	36
PRKCG	-0.038	0.12	-10000	0	-0.34	74	74
PRKCQ	-0.026	0.12	-10000	0	-0.41	48	48
FKBP38/BCL2	-0.011	0.086	-10000	0	-0.28	50	50
EP300	0.011	0.003	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.011	0	-10000	0	-10000	0	0
NFATc/JNK1	0.036	0.053	-10000	0	-0.29	2	2
CaM/Ca2+/FKBP38	0.015	0.004	-10000	0	-10000	0	0
FKBP12/FK506	0.008	0	-10000	0	-10000	0	0
CSNK1A1	0.015	0.005	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0.011	0.03	-10000	0	-0.2	10	10
NFATc/ERK1	0.039	0.048	-10000	0	-0.28	2	2
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.032	0.081	-10000	0	-0.35	22	22
NR4A1	0.015	0.12	-10000	0	-0.4	36	36
GSK3B	0.011	0.003	-10000	0	-10000	0	0
positive T cell selection	0.018	0.016	-10000	0	-0.31	1	1
NFAT1/CK1 alpha	-0.01	0.028	-10000	0	-0.22	3	3
RCH1/ KPNB1	0.006	0.048	-10000	0	-0.22	24	24
YWHAQ	0.011	0	-10000	0	-10000	0	0
PRKACA	0.011	0.003	-10000	0	-10000	0	0
AKAP5	0.009	0.031	-10000	0	-0.41	3	3
MEF2D	0.011	0.003	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.011	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.038	0.049	-10000	0	-0.29	2	2
CREBBP	0.009	0.026	-10000	0	-0.41	2	2
BCL2	-0.028	0.12	-10000	0	-0.41	50	50

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.027	0.025	-9999	-10000	0	0
PLK1	-0.088	0.18	-9999	-0.53	56	56
CDKN1B	0.002	0.14	-9999	-0.44	27	27
FOXO3	-0.05	0.18	-9999	-0.51	56	56
KAT2B	-0.002	0.057	-9999	-0.42	9	9
FOXO1/SIRT1	0.022	0.03	-9999	-10000	0	0
CAT	-0.039	0.17	-9999	-0.55	20	20
CTNNB1	0.011	0	-9999	-10000	0	0
AKT1	0.007	0.016	-9999	-10000	0	0
FOXO1	0.026	0.026	-9999	-0.22	5	5
MAPK10	-0.019	0.09	-9999	-0.19	115	115
mol:GTP	0.002	0.001	-9999	-10000	0	0
FOXO4	0.037	0.076	-9999	-0.29	5	5
response to oxidative stress	-0.005	0.018	-9999	-10000	0	0
FOXO3A/SIRT1	-0.073	0.15	-9999	-0.47	59	59
XPO1	0.012	0	-9999	-10000	0	0
EP300	0.012	0.001	-9999	-10000	0	0
BCL2L11	0.011	0.025	-9999	-10000	0	0
FOXO1/SKP2	0.029	0.023	-9999	-10000	0	0
mol:GDP	-0.005	0.018	-9999	-10000	0	0
RAN	0.012	0	-9999	-10000	0	0
GADD45A	0.012	0.096	-9999	-0.42	2	2
YWHAQ	0.011	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.033	0.017	-9999	-10000	0	0
MST1	0.001	0.042	-9999	-0.34	7	7
CSNK1D	0.011	0	-9999	-10000	0	0
CSNK1E	0.011	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.011	0.021	-9999	-10000	0	0
YWHAB	0.011	0	-9999	-10000	0	0
MAPK8	0.024	0.024	-9999	-0.19	6	6
MAPK9	0.026	0.008	-9999	-10000	0	0
YWHAG	0.011	0	-9999	-10000	0	0
YWHAE	0.011	0	-9999	-10000	0	0
YWHAZ	0.011	0	-9999	-10000	0	0
SIRT1	0.009	0.026	-9999	-0.41	2	2
SOD2	0.019	0.12	-9999	-0.45	3	3
RBL2	-0.014	0.15	-9999	-0.7	7	7
RAL/GDP	0.016	0.012	-9999	-10000	0	0
CHUK	0.005	0.016	-9999	-10000	0	0
Ran/GTP	0.011	0.001	-9999	-10000	0	0
CSNK1G2	0.011	0	-9999	-10000	0	0
RAL/GTP	0.022	0.012	-9999	-10000	0	0
CSNK1G1	0.011	0	-9999	-10000	0	0
FASLG	-0.001	0.12	-9999	-1.3	4	4
SKP2	0.011	0	-9999	-10000	0	0
USP7	0.012	0	-9999	-10000	0	0
IKBKB	0.005	0.016	-9999	-10000	0	0
CCNB1	-0.051	0.18	-9999	-0.61	21	21
FOXO1-3a-4/beta catenin	0.034	0.11	-9999	-0.37	7	7
proteasomal ubiquitin-dependent protein catabolic process	0.029	0.023	-9999	-10000	0	0
CSNK1A1	0.011	0	-9999	-10000	0	0
SGK1	0.003	0.031	-9999	-0.44	2	2
CSNK1G3	0.011	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.02	0.002	-9999	-10000	0	0
ZFAND5	0.042	0.067	-9999	-10000	0	0
SFN	-0.24	0.15	-9999	-0.33	395	395
CDK2	0.013	0.002	-9999	-10000	0	0
FOXO3A/14-3-3	0.004	0.035	-9999	-10000	0	0
CREBBP	0.011	0.026	-9999	-0.41	2	2
FBXO32	-0.13	0.41	-9999	-1.2	69	69
BCL6	-0.013	0.14	-9999	-0.67	5	5
RALB	0.012	0	-9999	-10000	0	0
RALA	0.012	0	-9999	-10000	0	0
YWHAH	0.011	0	-9999	-10000	0	0

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.007	0.045	-9999	-10000	0	0
epithelial cell differentiation	-0.04	0.076	-9999	-0.35	9	9
ITCH	0.017	0.011	-9999	-10000	0	0
WWP1	0.007	0.042	-9999	-10000	0	0
FYN	0.011	0	-9999	-10000	0	0
EGFR	0	0.066	-9999	-0.4	14	14
PRL	-0.01	0.083	-9999	-0.39	24	24
neuron projection morphogenesis	0.03	0.049	-9999	-10000	0	0
PTPRZ1	-0.014	0.08	-9999	-0.33	32	32
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.022	0.053	-9999	-0.27	2	2
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	0.005	0.059	-9999	-0.3	6	6
ADAM17	0.017	0.011	-9999	-10000	0	0
ErbB4/ErbB4	0.003	0.053	-9999	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.008	0.057	-9999	-0.28	2	2
NCOR1	0.011	0	-9999	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	0.011	0.055	-9999	-0.28	6	6
GRIN2B	0.007	0.062	-9999	-0.34	3	3
ErbB4/ErbB2/betacellulin	0.007	0.056	-9999	-0.29	3	3
STAT1	0.01	0.015	-9999	-0.33	1	1
HBEGF	0.011	0	-9999	-10000	0	0
PRLR	-0.072	0.17	-9999	-0.41	106	106
E4ICDs/ETO2	-0.026	0.095	-9999	-0.34	10	10
axon guidance	0.014	0.037	-9999	-10000	0	0
NEDD4	-0.018	0.11	-9999	-0.41	42	42
Prolactin receptor/Prolactin receptor/Prolactin	-0.056	0.13	-9999	-0.29	123	123
CBFA2T3	-0.049	0.15	-9999	-0.41	77	77
ErbB4/ErbB2/HBEGF	0.015	0.042	-9999	-10000	0	0
MAPK3	0.025	0.05	-9999	-10000	0	0
STAT1 (dimer)	0.007	0.046	-9999	-0.28	1	1
MAPK1	0.025	0.05	-9999	-10000	0	0
JAK2	0.004	0.054	-9999	-0.41	9	9
ErbB4/ErbB2/neuregulin 1 beta	0.007	0.061	-9999	-0.29	7	7
NRG1	0.009	0.058	-9999	-0.28	21	21
NRG3	-0.008	0.068	-9999	-0.33	23	23
NRG2	-0.05	0.15	-9999	-0.41	78	78
NRG4	-0.02	0.097	-9999	-0.33	48	48
heart development	0.014	0.037	-9999	-10000	0	0
neural crest cell migration	0.007	0.061	-9999	-0.28	7	7
ERBB2	0.015	0.039	-9999	-0.22	14	14
WWOX/E4ICDs	0.007	0.045	-9999	-10000	0	0
SHC1	0.011	0	-9999	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.006	0.077	-9999	-0.34	8	8
apoptosis	0.007	0.037	-9999	-10000	0	0
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.027	0.095	-9999	-0.34	12	12
ErbB4/ErbB2/epiregulin	-0.009	0.068	-9999	-0.3	3	3
ErbB4/ErbB4/betacellulin/betacellulin	-0.001	0.062	-9999	-0.36	3	3
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.031	0.11	-9999	-0.37	16	16
MDM2	0.009	0.046	-9999	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	0.011	0.051	-9999	-0.26	6	6
STAT5A	0.018	0.036	-9999	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	0.006	0.067	-9999	-0.32	10	10
DLG4	0.009	0.031	-9999	-0.41	3	3
GRB2/SHC	0.016	0	-9999	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.011	0.033	-9999	-10000	0	0
STAT5A (dimer)	-0.042	0.08	-9999	-0.38	8	8
MAP3K7IP2	0	0	-9999	-10000	0	0
STAT5B (dimer)	0.018	0.038	-9999	-0.32	1	1
LRIG1	0.009	0.031	-9999	-0.41	3	3
EREG	-0.034	0.11	-9999	-0.33	69	69
BTC	-0.003	0.076	-9999	-0.41	18	18
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.016	0.035	-9999	-10000	0	0
ERBB4	0.003	0.053	-9999	-10000	0	0
STAT5B	0.009	0.026	-9999	-0.41	2	2
YAP1	-0.001	0.023	-9999	-0.52	1	1
GRB2	0.011	0	-9999	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0	0.067	-9999	-0.29	6	6
glial cell differentiation	0.011	0.033	-9999	-10000	0	0
WWOX	0.011	0	-9999	-10000	0	0
cell proliferation	0.01	0.069	-9999	-0.3	1	1

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	-0.069	0.088	-9999	-0.28	1	1
CaM/Ca2+	0.008	0	-9999	-10000	0	0
AKT1	0.011	0	-9999	-10000	0	0
AKT2	0.011	0	-9999	-10000	0	0
STXBP4	0.01	0.018	-9999	-0.41	1	1
mol:GTP	0	0	-9999	-10000	0	0
mol:glucose	-0.074	0.1	-9999	-0.31	1	1
YWHAZ	0.011	0	-9999	-10000	0	0
CALM1	0.011	0	-9999	-10000	0	0
YWHAQ	0.011	0	-9999	-10000	0	0
TBC1D4	0.016	0.026	-9999	-0.28	4	4
mol:Ca2+	0	0	-9999	-10000	0	0
YWHAH	0.011	0	-9999	-10000	0	0
YWHAB	0.011	0	-9999	-10000	0	0
SNARE/Synip	0.022	0.011	-9999	-0.23	1	1
YWHAG	0.011	0	-9999	-10000	0	0
ASIP	0.007	0.015	-9999	-0.33	1	1
PRKCI	0.011	0	-9999	-10000	0	0
AS160/CaM/Ca2+	0.008	0	-9999	-10000	0	0
RHOQ	0.011	0	-9999	-10000	0	0
GYS1	0.025	0	-9999	-10000	0	0
PRKCZ	0.01	0.023	-9999	-0.37	2	2
TRIP10	0.011	0	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.015	0	-9999	-10000	0	0
AS160/14-3-3	-0.006	0.029	-9999	-10000	0	0
VAMP2	0.011	0	-9999	-10000	0	0
SLC2A4	-0.08	0.11	-9999	-0.34	1	1
STX4	0.011	0	-9999	-10000	0	0
GSK3B	0.021	0	-9999	-10000	0	0
SFN	-0.24	0.15	-9999	-0.33	395	395
LNPEP	0.011	0	-9999	-10000	0	0
YWHAE	0.011	0	-9999	-10000	0	0

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.011	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.014	0.082	-9999	-10000	0	0
Syndecan-3/Neurocan	0.006	0.028	-9999	-10000	0	0
POMC	-0.012	0.088	-9999	-0.35	33	33
EGFR	0	0.066	-9999	-0.4	14	14
Syndecan-3/EGFR	0.015	0.032	-9999	-10000	0	0
AGRP	0.006	0.015	-9999	-0.33	1	1
NCSTN	0.011	0	-9999	-10000	0	0
PSENEN	0.011	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.006	0.048	-9999	-0.41	7	7
APH1A	0.011	0	-9999	-10000	0	0
NCAN	-0.005	0.059	-9999	-0.33	17	17
long-term memory	0.026	0.006	-9999	-10000	0	0
Syndecan-3/IL8	-0.026	0.072	-9999	-10000	0	0
PSEN1	0.011	0	-9999	-10000	0	0
Src/Cortactin	0.016	0	-9999	-10000	0	0
FYN	0.011	0	-9999	-10000	0	0
limb bud formation	-0.001	0.005	-9999	-10000	0	0
MC4R	-0.004	0.056	-9999	-0.33	15	15
SRC	0.011	0	-9999	-10000	0	0
PTN	-0.088	0.18	-9999	-0.41	127	127
FGFR/FGF/Syndecan-3	-0.001	0.005	-9999	-10000	0	0
neuron projection morphogenesis	-0.025	0.078	-9999	-0.29	3	3
Syndecan-3/AgRP	0.011	0.013	-9999	-10000	0	0
Syndecan-3/AgRP/MC4R	0.004	0.027	-9999	-10000	0	0
Fyn/Cortactin	0.016	0	-9999	-10000	0	0
SDC3	-0.001	0.005	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.025	0.071	-9999	-10000	0	0
IL8	-0.089	0.16	-9999	-0.33	157	157
Syndecan-3/Fyn/Cortactin	0.026	0.006	-9999	-10000	0	0
Syndecan-3/CASK	-0.001	0.004	-9999	-10000	0	0
alpha-MSH/MC4R	-0.01	0.073	-9999	-0.24	46	46
Gamma Secretase	0.03	0.024	-9999	-0.18	7	7

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.016	0.084	-9999	-0.38	22	22
PDGFB-D/PDGFRB/SLAP	0.004	0.059	-9999	-0.28	23	23
PDGFB-D/PDGFRB/APS/CBL	0.013	0.049	-9999	-0.22	22	22
AKT1	0.035	0.047	-9999	-0.3	2	2
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.016	0.09	-9999	-0.41	22	22
PIK3CA	0.01	0.018	-9999	-0.41	1	1
FGR	-0.021	0.1	-9999	-0.38	31	31
mol:Ca2+	0.011	0.095	-9999	-0.44	22	22
MYC	0.022	0.13	-9999	-0.67	13	13
SHC1	0.011	0	-9999	-10000	0	0
HRAS/GDP	0.02	0.046	-9999	-0.24	3	3
LRP1/PDGFRB/PDGFB	0.012	0.053	-9999	-0.24	23	23
GRB10	0.01	0.018	-9999	-0.41	1	1
PTPN11	0.011	0	-9999	-10000	0	0
GO:0007205	0.011	0.096	-9999	-0.45	22	22
PTEN	0.006	0.044	-9999	-0.41	6	6
GRB2	0.011	0	-9999	-10000	0	0
GRB7	-0.01	0.083	-9999	-0.34	33	33
PDGFB-D/PDGFRB/SHP2	0.005	0.059	-9999	-0.28	22	22
PDGFB-D/PDGFRB/GRB10	0.004	0.06	-9999	-0.28	23	23
cell cycle arrest	0.004	0.059	-9999	-0.28	23	23
HRAS	0.011	0	-9999	-10000	0	0
HIF1A	0.039	0.043	-9999	-0.26	2	2
GAB1	0.015	0.092	-9999	-0.41	22	22
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.019	0.085	-9999	-0.37	22	22
PDGFB-D/PDGFRB	0.013	0.051	-9999	-0.23	22	22
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.005	0.059	-9999	-0.28	22	22
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.015	0.071	-9999	-0.34	22	22
positive regulation of MAPKKK cascade	0.005	0.058	-9999	-0.28	22	22
PIK3R1	0.007	0.04	-9999	-0.41	5	5
mol:IP3	0.011	0.097	-9999	-0.45	22	22
E5	0	0.001	-9999	-10000	0	0
CSK	0.01	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.01	0.083	-9999	-0.26	52	52
SHB	0.011	0	-9999	-10000	0	0
BLK	-0.011	0.052	-9999	-0.26	22	22
PTPN2	0.011	0.002	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.005	0.059	-9999	-0.28	22	22
BCAR1	0.011	0	-9999	-10000	0	0
VAV2	0.018	0.095	-9999	-0.39	23	23
CBL	0.011	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.005	0.059	-9999	-0.28	22	22
LCK	-0.011	0.065	-9999	-0.29	22	22
PDGFRB	-0.006	0.084	-9999	-0.41	22	22
ACP1	0.011	0	-9999	-10000	0	0
HCK	-0.01	0.052	-9999	-0.26	22	22
ABL1	0.016	0.078	-9999	-0.34	22	22
PDGFB-D/PDGFRB/CBL	0.012	0.1	-9999	-0.47	22	22
PTPN1	0.011	0.002	-9999	-10000	0	0
SNX15	0.011	0	-9999	-10000	0	0
STAT3	0.011	0	-9999	-10000	0	0
STAT1	0.01	0.015	-9999	-0.33	1	1
cell proliferation	0.023	0.11	-9999	-0.59	13	13
SLA	0.01	0.015	-9999	-0.33	1	1
actin cytoskeleton reorganization	0.032	0.043	-9999	-0.35	1	1
SRC	-0.009	0.052	-9999	-0.26	22	22
PI3K	-0.01	0.039	-9999	-0.33	2	2
PDGFB-D/PDGFRB/GRB7/SHC	0	0.07	-9999	-0.21	52	52
SH2B2	0.011	0	-9999	-10000	0	0
PLCgamma1/SPHK1	0.016	0.092	-9999	-0.42	22	22
LYN	-0.009	0.052	-9999	-0.26	22	22
LRP1	0.009	0.026	-9999	-0.41	2	2
SOS1	0.011	0	-9999	-10000	0	0
STAT5B	0.009	0.026	-9999	-0.41	2	2
STAT5A	0.01	0.018	-9999	-0.41	1	1
NCK1-2/p130 Cas	-0.004	0.039	-9999	-0.36	1	1
SPHK1	0.01	0.021	-9999	-0.33	2	2
EDG1	0.001	0.002	-9999	-10000	0	0
mol:DAG	0.011	0.097	-9999	-0.45	22	22
PLCG1	0.011	0.099	-9999	-0.46	22	22
NHERF/PDGFRB	0.011	0.052	-9999	-0.22	26	26
YES1	-0.011	0.051	-9999	-0.26	22	22
cell migration	0.011	0.051	-9999	-0.22	26	26
SHC/Grb2/SOS1	-0.003	0.036	-9999	-10000	0	0
SLC9A3R2	0.011	0	-9999	-10000	0	0
SLC9A3R1	0.008	0.029	-9999	-0.33	4	4
NHERF1-2/PDGFRB/PTEN	0.016	0.054	-9999	-0.2	27	27
FYN	-0.009	0.052	-9999	-0.26	22	22
DOK1	0.017	0.045	-9999	-0.2	22	22
HRAS/GTP	0.008	0	-9999	-10000	0	0
PDGFB	0.011	0	-9999	-10000	0	0
RAC1	0.024	0.1	-9999	-0.37	32	32
PRKCD	0.018	0.045	-9999	-0.2	22	22
FER	0.018	0.045	-9999	-0.2	22	22
MAPKKK cascade	-0.006	0.033	-9999	-10000	0	0
RASA1	0.016	0.052	-9999	-0.21	26	26
NCK1	0.009	0.026	-9999	-0.41	2	2
NCK2	0.011	0	-9999	-10000	0	0
p62DOK/Csk	0.022	0.042	-9999	-0.18	22	22
PDGFB-D/PDGFRB/SHB	0.005	0.059	-9999	-0.28	22	22
chemotaxis	0.016	0.076	-9999	-0.34	22	22
STAT1-3-5/STAT1-3-5	-0.008	0.035	-9999	-0.35	1	1
Bovine Papilomavirus E5/PDGFRB	-0.003	0.059	-9999	-0.29	22	22
PTPRJ	0.011	0	-9999	-10000	0	0

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.02	0.11	-10000	0	-0.44	6	6
CRKL	0.019	0.054	-10000	0	-0.24	6	6
mol:DAG	0.019	0.066	-10000	0	-0.24	19	19
HRAS	0.035	0.05	-10000	0	-10000	0	0
MAPK8	0.015	0.048	-10000	0	-0.19	22	22
RAP1A	0.019	0.054	-10000	0	-0.24	6	6
GAB1	0.017	0.057	-10000	0	-0.24	8	8
MAPK14	0.018	0.041	-10000	0	-0.18	16	16
EPO	-0.003	0.073	-10000	0	-0.4	17	17
PLCG1	0.019	0.067	-10000	0	-0.24	19	19
EPOR/TRPC2/IP3 Receptors	0.007	0.038	-10000	0	-0.32	7	7
RAPGEF1	0.011	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.012	0.049	-10000	0	-0.22	18	18
GAB1/SHC/GRB2/SOS1	-0.012	0.036	-10000	0	-0.21	5	5
EPO/EPOR (dimer)	0.005	0.058	-10000	0	-0.26	24	24
IRS2	-0.007	0.086	-10000	0	-0.26	19	19
STAT1	0.018	0.088	-10000	0	-0.37	6	6
STAT5B	0.017	0.08	-10000	0	-0.25	21	21
cell proliferation	0.02	0.045	-10000	0	-0.21	2	2
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.013	0.04	-10000	0	-0.22	10	10
TEC	0.018	0.054	-10000	0	-0.24	6	6
SOCS3	0.009	0.026	-10000	0	-0.41	2	2
STAT1 (dimer)	0.018	0.087	-10000	0	-0.37	6	6
JAK2	0.004	0.054	-10000	0	-0.41	9	9
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
EPO/EPOR (dimer)/JAK2	0.024	0.06	-10000	0	-0.18	26	26
EPO/EPOR	0.005	0.058	-10000	0	-0.26	24	24
LYN	0.011	0.004	-10000	0	-10000	0	0
TEC/VAV2	0.025	0.053	-10000	0	-0.22	6	6
elevation of cytosolic calcium ion concentration	0.007	0.038	-10000	0	-0.32	7	7
SHC1	0.011	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	0.017	0.049	-10000	0	-0.22	16	16
mol:IP3	0.019	0.066	-10000	0	-0.24	19	19
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.002	0.085	-10000	0	-0.25	22	22
SH2B3	0.01	0.019	-10000	0	-0.41	1	1
NFKB1	0.018	0.042	-10000	0	-0.21	4	4
EPO/EPOR (dimer)/JAK2/SOCS3	-0.01	0.05	0.23	1	-0.22	27	28
PTPN6	0.013	0.056	-10000	0	-0.18	26	26
TEC/VAV2/GRB2	0.029	0.051	-10000	0	-0.21	6	6
EPOR	0.007	0.038	-10000	0	-0.32	7	7
INPP5D	0.01	0.018	-10000	0	-0.41	1	1
mol:GDP	-0.012	0.036	-10000	0	-0.21	5	5
SOS1	0.011	0	-10000	0	-10000	0	0
PLCG2	0.01	0.023	-10000	0	-0.37	2	2
CRKL/CBL/C3G	0.03	0.051	-10000	0	-0.21	6	6
VAV2	0.019	0.054	-10000	0	-0.24	6	6
CBL	0.019	0.054	-10000	0	-0.24	6	6
SHC/Grb2/SOS1	-0.012	0.036	-10000	0	-0.21	6	6
STAT5A	0.018	0.079	-10000	0	-0.25	20	20
GRB2	0.011	0	-10000	0	-10000	0	0
STAT5 (dimer)	0.023	0.11	-10000	0	-0.27	51	51
LYN/PLCgamma2	0.015	0.017	-10000	0	-0.25	2	2
PTPN11	0.011	0	-10000	0	-10000	0	0
BTK	0.018	0.057	-10000	0	-0.27	6	6
BCL2	-0.025	0.25	-10000	0	-0.79	50	50

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.011	0	-10000	0	-10000	0	0
mol:PIP3	-0.024	0.081	0.23	5	-0.25	56	61
FRAP1	0.008	0.019	-10000	0	-10000	0	0
AKT1	0	0.072	0.2	5	-0.2	56	61
INSR	0.011	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.008	0.002	-10000	0	-10000	0	0
mol:GTP	-0.016	0.049	-10000	0	-0.31	2	2
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.005	0.014	-10000	0	-10000	0	0
TSC2	0.011	0	-10000	0	-10000	0	0
RHEB/GDP	-0.014	0.041	-10000	0	-0.27	2	2
TSC1	0.01	0.018	-10000	0	-0.41	1	1
Insulin Receptor/IRS1	-0.017	0.093	-10000	0	-0.3	53	53
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.006	0.017	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.011	0	-10000	0	-10000	0	0
RPS6KB1	0.011	0.041	0.16	5	-0.21	2	7
MAP3K5	0.007	0.025	-10000	0	-0.32	3	3
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
apoptosis	0.007	0.025	-10000	0	-0.32	3	3
mol:LY294002	0	0	-10000	0	-0.001	53	53
EIF4B	0.016	0.038	0.16	5	-0.19	2	7
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.018	0.033	-10000	0	-0.17	2	2
eIF4E/eIF4G1/eIF4A1	-0.001	0.004	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	-0.01	0.09	-10000	0	-0.27	57	57
mTOR/RHEB/GTP/Raptor/GBL	0.017	0.029	0.15	5	-0.14	2	7
FKBP1A	0.011	0	-10000	0	-10000	0	0
RHEB/GTP	-0.014	0.04	-10000	0	-0.27	2	2
mol:Amino Acids	0	0	-10000	0	-0.001	53	53
FKBP12/Rapamycin	0.008	0.001	-10000	0	-10000	0	0
PDPK1	-0.021	0.073	0.21	5	-0.22	56	61
EIF4E	0.011	0	-10000	0	-10000	0	0
ASK1/PP5C	0.012	0.046	-10000	0	-0.58	3	3
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.014	0.002	-10000	0	-10000	0	0
TSC1/TSC2	0.011	0.061	-10000	0	-0.33	2	2
tumor necrosis factor receptor activity	0	0	0.001	53	-10000	0	53
RPS6	0.011	0	-10000	0	-10000	0	0
PPP5C	0.011	0	-10000	0	-10000	0	0
EIF4G1	0.011	0	-10000	0	-10000	0	0
IRS1	-0.026	0.099	-10000	0	-0.32	53	53
INS	0.001	0.003	-10000	0	-10000	0	0
PTEN	0.006	0.044	-10000	0	-0.41	6	6
PDK2	-0.021	0.073	0.21	5	-0.22	56	61
EIF4EBP1	0.012	0.007	-10000	0	-10000	0	0
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
PPP2R5D	0.013	0.018	-10000	0	-10000	0	0
peptide biosynthetic process	0.014	0.001	-10000	0	-10000	0	0
RHEB	0.011	0	-10000	0	-10000	0	0
EIF4A1	0.011	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	0.003	6	-0.002	2	8
EEF2	0.014	0.001	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.017	0.005	-10000	0	-10000	0	0

×

HIF-2-alpha transcription factor network

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
MMP14	-0.007	0.048	-10000	0	-1.1	1	1
oxygen homeostasis	-0.002	0.014	-10000	0	-10000	0	0
TCEB2	0.01	0.015	-10000	0	-0.33	1	1
TCEB1	0.011	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.017	0.04	-10000	0	-0.29	4	4
EPO	-0.023	0.21	-10000	0	-0.52	28	28
FIH (dimer)	0.009	0.013	-10000	0	-10000	0	0
APEX1	0.007	0.015	-10000	0	-10000	0	0
SERPINE1	-0.014	0.2	-10000	0	-0.54	16	16
FLT1	-0.012	0.061	-10000	0	-1.1	1	1
ADORA2A	-0.013	0.19	-10000	0	-0.49	16	16
germ cell development	-0.022	0.21	-10000	0	-0.52	27	27
SLC11A2	-0.013	0.19	-10000	0	-0.5	15	15
BHLHE40	-0.013	0.19	-10000	0	-0.49	16	16
HIF1AN	0.009	0.013	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.004	0.12	-10000	0	-0.34	8	8
ETS1	0.021	0.02	-10000	0	-0.42	1	1
CITED2	-0.036	0.18	-10000	0	-1	17	17
KDR	-0.065	0.26	-10000	0	-1.1	32	32
PGK1	-0.013	0.19	-10000	0	-0.49	16	16
SIRT1	0.009	0.026	-10000	0	-0.41	2	2
response to hypoxia	0	0.002	-10000	0	-10000	0	0
HIF2A/ARNT	-0.017	0.22	-10000	0	-0.55	18	18
EPAS1	0.011	0.088	-10000	0	-0.37	3	3
SP1	0.017	0.001	-10000	0	-10000	0	0
ABCG2	-0.14	0.3	-10000	0	-0.54	101	101
EFNA1	-0.013	0.2	-10000	0	-0.5	16	16
FXN	-0.013	0.19	-10000	0	-0.49	16	16
POU5F1	-0.023	0.21	-10000	0	-0.54	27	27
neuron apoptosis	0.017	0.21	0.54	18	-10000	0	18
EP300	0.011	0	-10000	0	-10000	0	0
EGLN3	0.006	0.034	-10000	0	-0.35	4	4
EGLN2	0.009	0.013	-10000	0	-10000	0	0
EGLN1	0.009	0.013	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.022	0.014	-10000	0	-0.23	1	1
VHL	0.01	0.018	-10000	0	-0.41	1	1
ARNT	0.007	0.015	-10000	0	-10000	0	0
SLC2A1	-0.013	0.19	-10000	0	-0.49	15	15
TWIST1	-0.039	0.23	-10000	0	-0.54	56	56
ELK1	0.016	0.01	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0	0.11	-10000	0	-0.42	3	3
VEGFA	-0.013	0.19	-10000	0	-0.49	16	16
CREBBP	0.009	0.026	-10000	0	-0.41	2	2

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.039	0.042	-9999	-0.54	1	1
UGCG	0.004	0.094	-9999	-0.63	11	11
AKT1/mTOR/p70S6K/Hsp90/TERT	0.022	0.099	-9999	-0.26	32	32
mol:GTP	0	0	-9999	-10000	0	0
mol:glucosylceramide	0.005	0.093	-9999	-0.62	11	11
mol:DAG	0	0.001	-9999	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.039	0.11	-9999	-0.34	60	60
FRAP1	0.019	0.15	-9999	-0.39	60	60
FOXO3	0.039	0.099	-9999	-0.36	17	17
AKT1	0.034	0.1	-9999	-0.38	17	17
GAB2	0.007	0.036	-9999	-0.41	4	4
SMPD1	0.017	0.02	-9999	-10000	0	0
SGMS1	0.017	0.02	-9999	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
mol:GDP	0.013	0.027	-9999	-0.24	6	6
CALM1	0.011	0	-9999	-10000	0	0
cell proliferation	0.02	0.074	-9999	-0.29	21	21
EIF3A	0.011	0	-9999	-10000	0	0
PI3K	0.016	0.032	-9999	-0.28	6	6
RPS6KB1	0.014	0.023	-9999	-10000	0	0
mol:sphingomyelin	0	0.001	-9999	-10000	0	0
natural killer cell activation	0	0.003	-9999	-0.012	9	9
JAK3	0.01	0.029	-9999	-0.33	4	4
PIK3R1	0.008	0.041	-9999	-0.41	5	5
JAK1	0.011	0.026	-9999	-0.41	2	2
NFKB1	0.01	0.018	-9999	-0.41	1	1
MYC	0.029	0.15	-9999	-0.82	12	12
MYB	0.012	0.047	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.039	0.072	-9999	-0.29	9	9
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.025	0.021	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.039	0.071	-9999	-0.28	9	9
Rac1/GDP	0.019	0.025	-9999	-0.2	6	6
T cell proliferation	0.042	0.068	-9999	-0.35	3	3
SHC1	0.011	0.004	-9999	-10000	0	0
RAC1	0.011	0	-9999	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.002	0.007	-9999	-10000	0	0
PRKCZ	0.043	0.07	-9999	-0.36	3	3
NF kappa B1 p50/RelA	-0.033	0.11	-9999	-0.34	60	60
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.034	0.045	-9999	-0.44	2	2
HSP90AA1	0.011	0	-9999	-10000	0	0
RELA	0.011	0	-9999	-10000	0	0
IL2RA	-0.003	0.067	-9999	-0.33	21	21
IL2RB	0.012	0.018	-9999	-0.41	1	1
TERT	-0.11	0.16	-9999	-0.33	196	196
E2F1	0.014	0.032	-9999	-10000	0	0
SOS1	0.011	0.004	-9999	-10000	0	0
RPS6	0.011	0	-9999	-10000	0	0
mol:cAMP	-0.001	0.003	-9999	-10000	0	0
PTPN11	0.011	0.004	-9999	-10000	0	0
IL2RG	0.006	0.047	-9999	-0.36	9	9
actin cytoskeleton organization	0.042	0.068	-9999	-0.35	3	3
GRB2	0.011	0.004	-9999	-10000	0	0
IL2	-0.005	0.06	-9999	-0.33	18	18
PIK3CA	0.011	0.019	-9999	-0.41	1	1
Rac1/GTP	0.024	0.025	-9999	-0.19	6	6
LCK	0.009	0.035	-9999	-0.34	5	5
BCL2	-0.019	0.26	-9999	-0.82	50	50

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	-0.003	0.052	0.36	11	-10000	0	11
PI3K Class IB/PDE3B	0.003	0.053	-10000	0	-0.36	11	11
PDE3B	0.003	0.053	-10000	0	-0.36	11	11

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.015	0.002	-9999	-10000	0	0
RAS family/GTP	0.009	0.05	-9999	-0.27	5	5
NFATC4	0.015	0.047	-9999	-0.33	2	2
ERBB2IP	0.011	0.001	-9999	-10000	0	0
HSP90 (dimer)	0.011	0	-9999	-10000	0	0
mammary gland morphogenesis	0.003	0.049	-9999	-0.22	11	11
JUN	-0.006	0.069	-9999	-0.34	4	4
HRAS	0.01	0.001	-9999	-10000	0	0
DOCK7	0.013	0.048	-9999	-0.32	2	2
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.002	0.053	-9999	-0.21	22	22
AKT1	0.009	0.001	-9999	-10000	0	0
BAD	0.015	0.001	-9999	-10000	0	0
MAPK10	-0.009	0.067	-9999	-0.22	12	12
mol:GTP	-0.001	0.001	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	0.004	0.052	-9999	-0.23	11	11
RAF1	0.011	0.055	-9999	-0.3	4	4
ErbB2/ErbB3/neuregulin 2	-0.027	0.085	-9999	-0.21	91	91
STAT3	0.001	0.003	-9999	-10000	0	0
cell migration	0.001	0.062	-9999	-0.2	17	17
mol:PI-3-4-5-P3	0	0.001	-9999	-10000	0	0
cell proliferation	-0.079	0.18	-9999	-0.54	17	17
FOS	-0.12	0.24	-9999	-0.47	166	166
NRAS	0.01	0.001	-9999	-10000	0	0
mol:Ca2+	0.003	0.049	-9999	-0.22	11	11
MAPK3	-0.043	0.13	-9999	-0.48	10	10
MAPK1	-0.043	0.13	-9999	-0.48	10	10
JAK2	0.011	0.053	-9999	-0.32	2	2
NF2	0	0.002	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0.01	0.052	-9999	-0.23	22	22
NRG1	-0.006	0.081	-9999	-0.41	21	21
GRB2/SOS1	0.016	0.001	-9999	-10000	0	0
MAPK8	0.004	0.058	-9999	-0.22	28	28
MAPK9	0.021	0.029	-9999	-0.16	2	2
ERBB2	-0.006	0.037	-9999	-0.23	14	14
ERBB3	0.008	0.032	-9999	-0.41	3	3
SHC1	0.01	0.001	-9999	-10000	0	0
RAC1	0.011	0	-9999	-10000	0	0
apoptosis	0.001	0.006	-9999	-10000	0	0
STAT3 (dimer)	0.017	0.003	-9999	-10000	0	0
RNF41	0.02	0.003	-9999	-10000	0	0
FRAP1	0.008	0.001	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.007	0.029	-9999	-0.23	2	2
ErbB2/ErbB2/HSP90 (dimer)	-0.005	0.029	-9999	-0.18	14	14
CHRNA1	-0.053	0.13	-9999	-0.37	10	10
myelination	0.019	0.044	-9999	-0.31	2	2
PPP3CB	0.005	0.045	-9999	-0.3	2	2
KRAS	0.01	0.015	-9999	-0.33	1	1
RAC1-CDC42/GDP	0.022	0.046	-9999	-0.34	2	2
NRG2	-0.05	0.15	-9999	-0.41	78	78
mol:GDP	0.01	0.052	-9999	-0.23	22	22
SOS1	0.011	0.001	-9999	-10000	0	0
MAP2K2	0.011	0.061	-9999	-0.3	5	5
SRC	0.011	0	-9999	-10000	0	0
mol:cAMP	0	0.001	-9999	-10000	0	0
PTPN11	0.014	0.048	-9999	-0.31	2	2
MAP2K1	-0.048	0.13	-9999	-0.43	15	15
heart morphogenesis	0.003	0.049	-9999	-0.22	11	11
RAS family/GDP	0.016	0.048	-9999	-0.27	4	4
GRB2	0.011	0.001	-9999	-10000	0	0
PRKACA	-0.001	0.003	-9999	-10000	0	0
CHRNE	0.006	0.022	-9999	-0.18	4	4
HSP90AA1	0.011	0	-9999	-10000	0	0
activation of caspase activity	-0.009	0.001	-9999	-10000	0	0
nervous system development	0.003	0.049	-9999	-0.22	11	11
CDC42	0.011	0	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class III

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
EP300	0.011	0	-10000	0	-10000	0	0
HDAC4	0.011	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.011	0.033	0.23	9	-10000	0	9
CDKN1A	-0.001	0.027	-10000	0	-0.61	1	1
KAT2B	0.004	0.054	-10000	0	-0.41	9	9
BAX	0.011	0	-10000	0	-10000	0	0
FOXO3	0	0.006	-10000	0	-10000	0	0
FOXO1	0.009	0.031	-10000	0	-0.41	3	3
FOXO4	0.016	0.022	-10000	0	-0.24	4	4
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.011	0	-10000	0	-10000	0	0
TAT	0.007	0.015	-10000	0	-0.33	1	1
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.015	0.078	-10000	0	-0.23	61	61
PPARGC1A	-0.078	0.17	-10000	0	-0.41	114	114
FHL2	0.007	0.04	-10000	0	-0.41	5	5
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	-0.001	0.018	-10000	0	-0.28	2	2
HIST2H4A	0.011	0.033	-10000	0	-0.23	9	9
SIRT1/FOXO3a	-0.001	0.015	0.13	1	-0.23	2	3
SIRT1	0.006	0.027	0.18	1	-0.41	2	3
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	-0.001	0.015	-10000	0	-0.23	2	2
SIRT1/Histone H1b	0.012	0.026	-10000	0	-0.22	4	4
apoptosis	0.001	0.015	0.23	2	-10000	0	2
SIRT1/PGC1A	-0.05	0.097	0.12	1	-0.24	115	116
p53/SIRT1	-0.001	0.026	0.36	1	-0.28	3	4
SIRT1/FOXO4	0.016	0.024	0.14	1	-0.2	6	7
FOXO1/FHL2/SIRT1	0.015	0.031	-10000	0	-0.2	10	10
HIST1H1E	0.012	0.025	-10000	0	-0.24	2	2
SIRT1/p300	-0.001	0.018	0.14	1	-0.28	2	3
muscle cell differentiation	0.015	0.066	0.27	10	-10000	0	10
TP53	0.006	0.019	0.18	1	-0.41	1	2
KU70/SIRT1/BAX	-0.001	0.015	-10000	0	-0.23	2	2
CREBBP	0.009	0.026	-10000	0	-0.41	2	2
MEF2D	0.011	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.001	0.021	0.14	1	-0.26	3	4
ACSS2	0.015	0.019	-10000	0	-0.28	2	2
SIRT1/PCAF/MYOD	-0.015	0.066	0.14	1	-0.27	10	11

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.017	0.05	-9999	-0.21	18	18
MAP4K1	0.003	0.052	-9999	-0.33	13	13
MAP3K8	0.009	0.031	-9999	-0.41	3	3
PRKCB	-0.014	0.099	-9999	-0.41	32	32
DBNL	0.011	0	-9999	-10000	0	0
CRKL	0.011	0	-9999	-10000	0	0
MAP3K1	0.029	0.038	-9999	-0.22	1	1
JUN	-0.011	0.14	-9999	-0.52	38	38
MAP3K7	0.029	0.038	-9999	-0.22	1	1
GRAP2	-0.002	0.074	-9999	-0.41	17	17
CRK	0.011	0	-9999	-10000	0	0
MAP2K4	0.034	0.039	-9999	-0.22	1	1
LAT	0.011	0	-9999	-10000	0	0
LCP2	0.01	0.015	-9999	-0.33	1	1
MAPK8	-0.014	0.15	-9999	-0.55	38	38
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.024	0.04	-9999	-0.24	1	1
LAT/GRAP2/SLP76/HPK1/HIP-55	0.022	0.047	-9999	-0.31	2	2

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.017	0.018	-10000	0	-0.28	2	2
MAP4K4	0.028	0.034	-10000	0	-0.4	1	1
BAG4	0.009	0.031	-10000	0	-0.41	3	3
PKC zeta/ceramide	-0.001	0.016	0.12	2	-0.18	2	4
NFKBIA	0.011	0	-10000	0	-10000	0	0
BIRC3	0.003	0.055	-10000	0	-0.39	10	10
BAX	0.002	0.006	-10000	0	-10000	0	0
RIPK1	0.011	0	-10000	0	-10000	0	0
AKT1	0.014	0.002	-10000	0	-10000	0	0
BAD	-0.002	0.012	0.13	2	-10000	0	2
SMPD1	0.015	0.025	-10000	0	-0.17	2	2
RB1	-0.003	0.02	0.13	2	-0.22	3	5
FADD/Caspase 8	0.036	0.032	-10000	0	-0.39	1	1
MAP2K4	0.003	0.014	0.13	2	-0.19	1	3
NSMAF	0.011	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.003	0.016	0.13	2	-0.19	2	4
EGF	-0.005	0.07	-10000	0	-0.34	23	23
mol:ceramide	-0.009	0.013	0.13	2	-10000	0	2
MADD	0.011	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.017	0.018	-10000	0	-0.28	2	2
ASAH1	0.011	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.003	0.02	0.13	2	-0.22	3	5
cell proliferation	-0.011	0.069	-10000	0	-0.2	8	8
BID	0.024	0.025	-10000	0	-0.29	1	1
MAP3K1	-0.002	0.012	0.13	2	-10000	0	2
EIF2A	0.009	0.011	0.14	1	-10000	0	1
TRADD	0.011	0	-10000	0	-10000	0	0
CRADD	0.011	0	-10000	0	-10000	0	0
MAPK3	0.012	0.015	0.13	2	-0.17	2	4
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.012	0.015	0.14	1	-0.17	2	3
Cathepsin D/ceramide	-0.001	0.014	0.12	2	-0.16	1	3
FADD	0.028	0.034	-10000	0	-0.4	1	1
KSR1	-0.003	0.017	0.13	2	-0.21	2	4
MAPK8	0.005	0.028	0.13	2	-0.22	7	9
PRKRA	-0.002	0.012	0.13	2	-10000	0	2
PDGFA	0.009	0.026	-10000	0	-0.41	2	2
TRAF2	0.011	0	-10000	0	-10000	0	0
IGF1	-0.068	0.16	-10000	0	-0.41	101	101
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.009	0.013	0.13	2	-10000	0	2
CTSD	0.01	0.015	-10000	0	-0.33	1	1
regulation of nitric oxide biosynthetic process	0.016	0.013	-10000	0	-0.28	1	1
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.011	0.074	-10000	0	-0.21	8	8
PRKCD	0.011	0	-10000	0	-10000	0	0
PRKCZ	0.01	0.023	-10000	0	-0.37	2	2
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.017	0.018	-10000	0	-0.28	2	2
RelA/NF kappa B1	0.016	0.013	-10000	0	-0.28	1	1
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.011	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.024	0.036	-10000	0	-0.19	9	9
TNFR1A/BAG4/TNF-alpha	-0.003	0.067	-10000	0	-0.18	70	70
mol:Sphingosine-1-phosphate	0.017	0.018	-10000	0	-0.28	2	2
MAP2K1	0.008	0.016	0.14	1	-0.18	2	3
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.011	0	-10000	0	-10000	0	0
CYCS	0.014	0.04	0.14	51	-10000	0	51
TNFRSF1A	0.011	0	-10000	0	-10000	0	0
NFKB1	0.01	0.018	-10000	0	-0.41	1	1
TNFR1A/BAG4	0.015	0.022	-10000	0	-0.28	3	3
EIF2AK2	0.004	0.011	0.13	2	-10000	0	2
TNF-alpha/TNFR1A/FAN	-0.002	0.065	-10000	0	-0.18	67	67
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.03	0.023	-10000	0	-0.22	1	1
MAP2K2	0.008	0.016	0.14	1	-0.18	2	3
SMPD3	0.016	0.032	-10000	0	-0.28	3	3
TNF	-0.032	0.11	-10000	0	-0.33	67	67
PKC zeta/PAR4	0.015	0.016	-10000	0	-0.25	2	2
mol:PHOSPHOCHOLINE	-0.005	0.021	0.16	3	-10000	0	3
NF kappa B1/RelA/I kappa B alpha	0.032	0.015	-10000	0	-10000	0	0
AIFM1	0.014	0.04	0.14	51	-10000	0	51
BCL2	-0.028	0.12	-10000	0	-0.41	50	50

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.023	0.02	-9999	-0.28	2	2
CRKL	0.011	0	-9999	-10000	0	0
Rac1/GDP	0.008	0	-9999	-10000	0	0
DOCK1	0.006	0.048	-9999	-0.41	7	7
ITGA4	0.009	0.029	-9999	-0.38	3	3
alpha4/beta7 Integrin/MAdCAM1	0.013	0.049	-9999	-0.2	2	2
EPO	-0.005	0.073	-9999	-0.4	17	17
alpha4/beta7 Integrin	0.014	0.023	-9999	-0.25	4	4
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.011	0	-9999	-10000	0	0
alpha4/beta1 Integrin	0.015	0.021	-9999	-0.26	3	3
EPO/EPOR (dimer)	0.002	0.057	-9999	-0.26	24	24
lamellipodium assembly	0.025	0.028	-9999	-0.24	6	6
PIK3CA	0.01	0.018	-9999	-0.41	1	1
PI3K	0.013	0.031	-9999	-0.28	6	6
ARF6	0.011	0	-9999	-10000	0	0
JAK2	0.012	0.056	-9999	-0.22	27	27
PXN	0.011	0	-9999	-10000	0	0
PIK3R1	0.007	0.04	-9999	-0.41	5	5
MADCAM1	-0.016	0.089	-9999	-0.33	40	40
cell adhesion	0.012	0.049	-9999	-0.2	2	2
CRKL/CBL	0.016	0	-9999	-10000	0	0
ITGB1	0.011	0	-9999	-10000	0	0
SRC	0.009	0.063	-9999	-0.21	40	40
ITGB7	0.01	0.015	-9999	-0.33	1	1
RAC1	0.011	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.003	0.07	-9999	-0.24	41	41
p130Cas/Crk/Dock1	0.023	0.06	-9999	-0.43	2	2
VCAM1	-0.02	0.11	-9999	-0.41	40	40
RHOA	0.011	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.027	0.016	-9999	-0.2	2	2
BCAR1	0.015	0.059	-9999	-0.19	40	40
EPOR	0.007	0.039	-9999	-0.33	7	7
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.011	0	-9999	-10000	0	0
GIT1	0.011	0	-9999	-10000	0	0
Rac1/GTP	-0.002	0.026	-9999	-0.24	6	6

×

ceramide signaling pathway

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
MAP4K4	0.032	0.038	-10000	0	-0.24	8	8
BAG4	0.009	0.031	-10000	0	-0.41	3	3
BAD	0.023	0.014	-10000	0	-0.12	1	1
NFKBIA	0.011	0	-10000	0	-10000	0	0
BIRC3	0.003	0.055	-10000	0	-0.39	10	10
BAX	0.023	0.014	-10000	0	-0.12	1	1
EnzymeConsortium:3.1.4.12	0.01	0.01	-10000	0	-0.056	8	8
IKBKB	0.037	0.037	-10000	0	-0.22	8	8
MAP2K2	0.031	0.017	-10000	0	-0.16	1	1
MAP2K1	0.031	0.017	-10000	0	-0.16	1	1
SMPD1	0.015	0.01	-10000	0	-10000	0	0
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.038	0.037	-10000	0	-0.22	8	8
MAP2K4	0.027	0.016	-10000	0	-0.15	1	1
protein ubiquitination	0.038	0.037	-10000	0	-0.22	8	8
EnzymeConsortium:2.7.1.37	0.035	0.018	-10000	0	-0.16	1	1
response to UV	0	0	-10000	0	-0.002	1	1
RAF1	0.027	0.018	-10000	0	-0.16	2	2
CRADD	0.011	0	-10000	0	-10000	0	0
mol:ceramide	0.018	0.014	-10000	0	-0.13	1	1
I-kappa-B-alpha/RELA/p50/ubiquitin	0.015	0	-10000	0	-10000	0	0
MADD	0.011	0	-10000	0	-10000	0	0
MAP3K1	0.023	0.014	-10000	0	-0.12	1	1
TRADD	0.011	0	-10000	0	-10000	0	0
RELA/p50	0.011	0	-10000	0	-10000	0	0
MAPK3	0.033	0.017	-10000	0	-0.16	1	1
MAPK1	0.033	0.017	-10000	0	-0.16	1	1
p50/RELA/I-kappa-B-alpha	0.016	0	-10000	0	-10000	0	0
FADD	0.032	0.038	-10000	0	-0.24	8	8
KSR1	0.023	0.018	-10000	0	-0.16	3	3
MAPK8	0.03	0.024	-10000	0	-0.15	7	7
TRAF2	0.011	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	0.037	0.037	-10000	0	-0.22	8	8
TNF R/SODD	0.015	0.022	-10000	0	-0.28	3	3
TNF	-0.031	0.11	-10000	0	-0.33	67	67
CYCS	0.032	0.03	0.12	47	-0.11	1	48
IKBKG	0.037	0.037	-10000	0	-0.22	8	8
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.028	0.04	-10000	0	-0.25	8	8
RELA	0.011	0	-10000	0	-10000	0	0
RIPK1	0.011	0	-10000	0	-10000	0	0
AIFM1	0.032	0.03	0.12	47	-0.11	1	48
TNF/TNF R/SODD	-0.003	0.067	-10000	0	-0.18	70	70
TNFRSF1A	0.011	0	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.023	0.011	-10000	0	-10000	0	0
NSMAF	0.032	0.038	-10000	0	-0.23	8	8
response to hydrogen peroxide	0	0	-10000	0	-0.002	1	1
BCL2	-0.028	0.12	-10000	0	-0.41	50	50

×

IL27-mediated signaling events

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
TGFB1	0.011	0.018	-10000	0	-0.4	1	1
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.01	0.096	0.46	5	-10000	0	5
IL27/IL27R/JAK1	-0.015	0.11	-10000	0	-0.84	3	3
TBX21	0.002	0.11	-10000	0	-0.56	6	6
IL12B	0.006	0.016	-10000	0	-0.33	1	1
IL12A	0.001	0.042	-10000	0	-0.24	15	15
IL6ST	-0.053	0.15	-10000	0	-0.42	81	81
IL27RA/JAK1	0.012	0.072	-10000	0	-1.1	2	2
IL27	0.001	0.051	-10000	0	-0.33	12	12
TYK2	0.012	0.005	-10000	0	-10000	0	0
T-helper cell lineage commitment	0	0.047	-10000	0	-10000	0	0
T-helper 2 cell differentiation	0.01	0.096	0.46	5	-10000	0	5
T cell proliferation during immune response	0.01	0.096	0.46	5	-10000	0	5
MAPKKK cascade	-0.01	0.096	-10000	0	-0.46	5	5
STAT3	0.011	0	-10000	0	-10000	0	0
STAT2	0.011	0	-10000	0	-10000	0	0
STAT1	0.011	0.015	-10000	0	-0.34	1	1
IL12RB1	-0.001	0.066	-10000	0	-0.35	18	18
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.002	0.12	-10000	0	-0.47	11	11
IL27/IL27R/JAK2/TYK2	-0.01	0.097	-10000	0	-0.47	5	5
positive regulation of T cell mediated cytotoxicity	-0.01	0.096	-10000	0	-0.46	5	5
STAT1 (dimer)	-0.04	0.12	0.47	4	-0.78	4	8
JAK2	0.004	0.054	-10000	0	-0.41	9	9
JAK1	0.01	0.026	-10000	0	-0.41	2	2
STAT2 (dimer)	-0.004	0.092	-10000	0	-0.44	5	5
T cell proliferation	-0.011	0.1	-10000	0	-0.42	11	11
IL12/IL12R/TYK2/JAK2	0.014	0.052	-10000	0	-0.52	1	1
IL17A	-0.002	0.047	-10000	0	-10000	0	0
mast cell activation	0.01	0.096	0.46	5	-10000	0	5
IFNG	0	0.022	-10000	0	-0.075	4	4
T cell differentiation	-0.002	0.004	-10000	0	-0.019	6	6
STAT3 (dimer)	-0.004	0.092	-10000	0	-0.44	5	5
STAT5A (dimer)	-0.004	0.092	-10000	0	-0.44	5	5
STAT4 (dimer)	-0.004	0.092	-10000	0	-0.44	5	5
STAT4	0.01	0.018	-10000	0	-0.41	1	1
T cell activation	-0.007	0.009	0.12	2	-10000	0	2
IL27R/JAK2/TYK2	-0.014	0.11	-10000	0	-0.81	3	3
GATA3	-0.012	0.13	-10000	0	-1.2	6	6
IL18	0.005	0.03	-10000	0	-0.23	9	9
positive regulation of mast cell cytokine production	-0.004	0.091	-10000	0	-0.43	5	5
IL27/EBI3	0.005	0.056	-10000	0	-0.25	22	22
IL27RA	0.004	0.075	-10000	0	-1.2	2	2
IL6	-0.006	0.083	-10000	0	-0.38	25	25
STAT5A	0.01	0.018	-10000	0	-0.41	1	1
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	-0.002	0.037	0.46	2	-10000	0	2
IL1B	0.007	0.025	-10000	0	-0.29	4	4
EBI3	0.003	0.054	-10000	0	-0.34	13	13
TNF	-0.02	0.078	-10000	0	-0.23	67	67

×

Caspase cascade in apoptosis

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
TOP1	0.013	0.049	-10000	0	-0.29	6	6
ACTA1	0.004	0.058	0.16	3	-0.3	10	13
NUMA1	0.013	0.049	-10000	0	-0.29	6	6
SPTAN1	0.007	0.058	0.16	5	-0.3	10	15
LIMK1	0.007	0.058	0.17	1	-0.3	10	11
BIRC3	0.003	0.055	-10000	0	-0.39	10	10
BIRC2	0.011	0	-10000	0	-10000	0	0
BAX	0.011	0	-10000	0	-10000	0	0
CASP10	-0.002	0.075	-10000	0	-0.2	59	59
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.011	0	-10000	0	-10000	0	0
PTK2	0.013	0.049	-10000	0	-0.29	6	6
DIABLO	0.011	0	-10000	0	-10000	0	0
apoptotic nuclear changes	0.007	0.057	0.16	5	-0.3	10	15
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.011	0	-10000	0	-10000	0	0
GSN	0.004	0.06	0.16	4	-0.3	10	14
MADD	0.011	0	-10000	0	-10000	0	0
TFAP2A	0.028	0.039	-10000	0	-0.59	2	2
BID	0.008	0.037	-10000	0	-0.18	11	11
MAP3K1	0.008	0.024	-10000	0	-0.17	2	2
TRADD	0.011	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.016	0	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	0.007	0.058	0.16	5	-0.3	10	15
CASP9	0.011	0	-10000	0	-10000	0	0
DNA repair	-0.005	0.022	0.14	1	-0.16	5	6
neuron apoptosis	0.019	0.008	-10000	0	-10000	0	0
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.013	0.056	-10000	0	-0.34	6	6
APAF1	0.011	0	-10000	0	-10000	0	0
CASP6	0.022	0.032	-10000	0	-0.28	1	1
TRAF2	0.011	0	-10000	0	-10000	0	0
ICAD/CAD	0.012	0.056	-10000	0	-0.34	6	6
CASP7	-0.005	0.033	0.25	8	-10000	0	8
KRT18	0.013	0.032	-10000	0	-0.7	1	1
apoptosis	0.014	0.054	0.18	5	-0.28	6	11
DFFA	0.007	0.058	0.16	5	-0.3	10	15
DFFB	0.007	0.058	0.16	5	-0.3	10	15
PARP1	0.005	0.022	0.16	5	-0.14	1	6
actin filament polymerization	-0.009	0.058	0.28	11	-0.17	1	12
TNF	-0.032	0.11	-10000	0	-0.33	67	67
CYCS	0.009	0.031	-10000	0	-0.15	8	8
SATB1	-0.005	0.081	-10000	0	-0.37	5	5
SLK	0.007	0.058	0.17	1	-0.3	10	11
p15 BID/BAX	0.013	0.033	-10000	0	-0.26	2	2
CASP2	0.03	0.03	-10000	0	-0.3	1	1
JNK cascade	-0.008	0.023	0.17	2	-10000	0	2
CASP3	0.001	0.061	0.17	5	-0.32	10	15
LMNB2	0.032	0.024	-10000	0	-10000	0	0
RIPK1	0.011	0	-10000	0	-10000	0	0
CASP4	0.01	0.018	-10000	0	-0.41	1	1
Mammalian IAPs/DIABLO	0.024	0.029	-10000	0	-0.2	8	8
negative regulation of DNA binding	0.028	0.039	-10000	0	-0.58	2	2
stress fiber formation	0.007	0.057	0.16	5	-0.3	10	15
GZMB	-0.011	0.086	-10000	0	-0.25	58	58
CASP1	0.012	0.022	-10000	0	-0.28	3	3
LMNB1	0.032	0.024	-10000	0	-0.17	1	1
APP	0.02	0.008	-10000	0	-10000	0	0
TNFRSF1A	0.011	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.009	0	-10000	0	-10000	0	0
VIM	0.01	0.053	0.18	5	-0.27	6	11
LMNA	0.032	0.024	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.026	0.032	-10000	0	-0.32	1	1
LRDD	0.011	0	-10000	0	-10000	0	0
SREBF1	0.007	0.058	0.16	5	-0.3	10	15
APAF-1/Caspase 9	-0.001	0.017	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0.013	0.048	-10000	0	-0.29	6	6
CFL2	0.009	0.059	0.17	1	-0.28	11	12
GAS2	-0.008	0.081	0.17	4	-0.34	14	18
positive regulation of apoptosis	0.035	0.024	-10000	0	-10000	0	0
PRF1	0.005	0.05	-10000	0	-0.37	9	9

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	0.024	0.03	-9999	-0.2	9	9
HDAC3	0.011	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC4	0.013	0.004	-9999	-10000	0	0
GATA1/HDAC5	0.013	0.004	-9999	-10000	0	0
GATA2/HDAC5	-0.012	0.087	-9999	-0.28	51	51
HDAC5/BCL6/BCoR	0.022	0.011	-9999	-0.23	1	1
HDAC9	0.003	0.057	-9999	-0.41	10	10
Glucocorticoid receptor/Hsp90/HDAC6	-0.014	0.088	-9999	-0.23	79	79
HDAC4/ANKRA2	0.016	0.013	-9999	-0.28	1	1
HDAC5/YWHAB	0.016	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.017	0	-9999	-10000	0	0
GATA2	-0.029	0.12	-9999	-0.41	51	51
HDAC4/RFXANK	0.015	0.017	-9999	-0.22	3	3
BCOR	0.011	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.011	0	-9999	-10000	0	0
HDAC5	0.011	0	-9999	-10000	0	0
GNB1/GNG2	0.011	0.039	-9999	-0.27	10	10
Histones	0.029	0.027	-9999	-10000	0	0
ADRBK1	0.011	0	-9999	-10000	0	0
HDAC4	0.011	0	-9999	-10000	0	0
XPO1	0.011	0	-9999	-10000	0	0
HDAC5/ANKRA2	0.016	0.013	-9999	-0.28	1	1
HDAC4/Ubc9	0.016	0	-9999	-10000	0	0
HDAC7	0.011	0	-9999	-10000	0	0
HDAC5/14-3-3 E	0.016	0	-9999	-10000	0	0
TUBA1B	0.011	0	-9999	-10000	0	0
HDAC6	0.011	0	-9999	-10000	0	0
HDAC5/RFXANK	0.015	0.017	-9999	-0.22	3	3
CAMK4	0.003	0.051	-9999	-0.36	10	10
Tubulin/HDAC6	0.02	0.024	-9999	-0.19	7	7
SUMO1	0.011	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.011	0	-9999	-10000	0	0
GATA1	0.006	0.005	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.011	0	-9999	-10000	0	0
NR3C1	-0.051	0.15	-9999	-0.41	79	79
SUMO1/HDAC4	0.025	0	-9999	-10000	0	0
SRF	0.011	0	-9999	-10000	0	0
HDAC4/YWHAB	0.016	0	-9999	-10000	0	0
Tubulin	0.013	0.029	-9999	-0.24	7	7
HDAC4/14-3-3 E	0.016	0	-9999	-10000	0	0
GNB1	0.011	0	-9999	-10000	0	0
RANGAP1	0.011	0	-9999	-10000	0	0
BCL6/BCoR	0.016	0.013	-9999	-0.28	1	1
HDAC4/HDAC3/SMRT (N-CoR2)	0.022	0	-9999	-10000	0	0
HDAC4/SRF	0.018	0.03	-9999	-0.23	4	4
HDAC4/ER alpha	-0.017	0.094	-9999	-0.28	61	61
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.029	0.026	-9999	-10000	0	0
cell motility	0.019	0.024	-9999	-0.19	7	7
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.011	0	-9999	-10000	0	0
HDAC7/HDAC3	0.016	0	-9999	-10000	0	0
BCL6	0.01	0.018	-9999	-0.41	1	1
HDAC4/CaMK II delta B	0.011	0	-9999	-10000	0	0
Hsp90/HDAC6	0.016	0	-9999	-10000	0	0
ESR1	-0.037	0.13	-9999	-0.41	61	61
HDAC6/HDAC11	0.016	0.01	-9999	-0.22	1	1
Ran/GTP/Exportin 1	0.027	0	-9999	-10000	0	0
NPC	0.007	0	-9999	-10000	0	0
MEF2C	-0.03	0.12	-9999	-0.41	53	53
RAN	0.011	0	-9999	-10000	0	0
HDAC4/MEF2C	0.012	0.063	-9999	-10000	0	0
GNG2	0.003	0.056	-9999	-0.4	10	10
NCOR2	0.011	0	-9999	-10000	0	0
TUBB2A	0.006	0.041	-9999	-0.35	7	7
HDAC11	0.01	0.015	-9999	-0.33	1	1
HSP90AA1	0.011	0	-9999	-10000	0	0
RANBP2	0.011	0	-9999	-10000	0	0
ANKRA2	0.01	0.018	-9999	-0.41	1	1
RFXANK	0.009	0.025	-9999	-0.33	3	3
nuclear import	-0.024	0	-9999	-10000	0	0

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	0.018	0.23	-9999	-1.2	11	11
IL23A	0.018	0.21	-9999	-0.99	11	11
NF kappa B1 p50/RelA/I kappa B alpha	-0.042	0.16	-9999	-0.98	9	9
positive regulation of T cell mediated cytotoxicity	0.018	0.22	-9999	-1.1	9	9
ITGA3	0.023	0.2	-9999	-1	8	8
IL17F	0.032	0.15	-9999	-0.66	8	8
IL12B	0.015	0.025	-9999	-0.32	1	1
STAT1 (dimer)	0.018	0.21	-9999	-1	9	9
CD4	0.025	0.2	-9999	-0.99	8	8
IL23	0.014	0.2	-9999	-0.95	11	11
IL23R	0.021	0.053	-9999	-10000	0	0
IL1B	0.017	0.22	-9999	-1.1	10	10
T-helper cell lineage commitment	0	0	-9999	-10000	0	0
IL24	0.02	0.2	-9999	-1	8	8
TYK2	0.015	0.013	-9999	-10000	0	0
STAT4	0.01	0.018	-9999	-0.41	1	1
STAT3	0.011	0	-9999	-10000	0	0
IL18RAP	0.005	0.044	-9999	-0.38	7	7
IL12RB1	0.003	0.07	-9999	-0.36	18	18
PIK3CA	0.01	0.018	-9999	-0.41	1	1
IL12Rbeta1/TYK2	0.011	0.052	-9999	-0.25	18	18
IL23R/JAK2	0.028	0.076	-9999	-10000	0	0
positive regulation of chronic inflammatory response	0.018	0.22	-9999	-1.1	9	9
natural killer cell activation	-0.001	0.005	-9999	-10000	0	0
JAK2	0.013	0.06	-9999	-0.42	9	9
PIK3R1	0.007	0.04	-9999	-0.41	5	5
NFKB1	0.011	0.018	-9999	-0.41	1	1
RELA	0.012	0.002	-9999	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	0.016	0.2	-9999	-0.91	11	11
ALOX12B	0.019	0.2	-9999	-1	7	7
CXCL1	-0.003	0.24	-9999	-1.1	14	14
T cell proliferation	0.018	0.22	-9999	-1.1	9	9
NFKBIA	0.012	0.002	-9999	-10000	0	0
IL17A	0.043	0.13	-9999	-0.54	6	6
PI3K	-0.026	0.18	-9999	-1	9	9
IFNG	0.003	0.019	-9999	-10000	0	0
STAT3 (dimer)	-0.047	0.16	-9999	-0.96	9	9
IL18R1	0.007	0.036	-9999	-0.41	4	4
IL23/IL23R/JAK2/TYK2/SOCS3	0.03	0.14	-9999	-0.64	7	7
IL18/IL18R	0.014	0.045	-9999	-0.21	18	18
macrophage activation	-0.003	0.01	-9999	-0.041	12	12
TNF	0.015	0.22	-9999	-1.1	8	8
STAT3/STAT4	-0.024	0.18	-9999	-1	9	9
STAT4 (dimer)	0.018	0.21	-9999	-1	9	9
IL18	0.005	0.044	-9999	-0.33	9	9
IL19	0.006	0.2	-9999	-1	8	8
STAT5A (dimer)	0.018	0.21	-9999	-1.1	9	9
STAT1	0.01	0.015	-9999	-0.33	1	1
SOCS3	0.009	0.026	-9999	-0.41	2	2
CXCL9	0.004	0.23	-9999	-1.2	10	10
MPO	0.023	0.2	-9999	-0.99	8	8
positive regulation of humoral immune response	0.018	0.22	-9999	-1.1	9	9
IL23/IL23R/JAK2/TYK2	0.017	0.22	-9999	-1.1	9	9
IL6	0.002	0.27	-9999	-1.1	20	20
STAT5A	0.01	0.018	-9999	-0.41	1	1
IL2	-0.008	0.061	-9999	-0.33	18	18
positive regulation of tyrosine phosphorylation of STAT protein	-0.001	0.005	-9999	-10000	0	0
CD3E	0.014	0.24	-9999	-1.1	14	14
keratinocyte proliferation	0.018	0.22	-9999	-1.1	9	9
NOS2	0.014	0.23	-9999	-1.1	13	13

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.01	0.015	-10000	0	-0.2	3	3
TRAF2/ASK1	0.014	0.019	-10000	0	-0.23	3	3
ATM	0.011	0	-10000	0	-10000	0	0
MAP2K3	0.026	0.02	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.028	0.025	-10000	0	-0.22	3	3
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	-0.001	0.069	-10000	0	-0.41	15	15
TXN	0.007	0	-10000	0	-10000	0	0
CALM1	0.011	0	-10000	0	-10000	0	0
GADD45A	0.011	0	-10000	0	-10000	0	0
GADD45B	0.011	0	-10000	0	-10000	0	0
MAP3K1	0.011	0	-10000	0	-10000	0	0
MAP3K6	0.011	0	-10000	0	-10000	0	0
MAP3K7	0.011	0	-10000	0	-10000	0	0
MAP3K4	0.011	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.015	0.022	-10000	0	-0.28	3	3
TAK1/TAB family	0.001	0.009	0.15	2	-10000	0	2
RAC1/OSM/MEKK3	0.021	0	-10000	0	-10000	0	0
TRAF2	0.011	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.001	0.009	-10000	0	-10000	0	0
TRAF6	0.007	0	-10000	0	-10000	0	0
RAC1	0.011	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.046	0.13	-10000	0	-0.33	89	89
CCM2	0.011	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.017	0.073	-10000	0	-0.18	89	89
MAPK11	0.009	0.026	-10000	0	-0.41	2	2
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.009	0.067	-10000	0	-0.16	92	92
OSM/MEKK3	0.016	0	-10000	0	-10000	0	0
TAOK1	0.013	0.018	-10000	0	-0.28	2	2
TAOK2	0.014	0	-10000	0	-10000	0	0
TAOK3	0.014	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.011	0	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.009	0.031	-10000	0	-0.41	3	3
MAP3K10	0.011	0	-10000	0	-10000	0	0
MAP3K3	0.011	0	-10000	0	-10000	0	0
TRX/ASK1	0.012	0.018	-10000	0	-0.23	3	3
GADD45/MTK1/MTK1	0.02	0.035	-10000	0	-0.18	15	15

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.009	0.031	-9999	-0.41	3	3
Caspase 8 (4 units)	0.03	0.034	-9999	-0.36	1	1
NEF	0.001	0.019	-9999	-0.16	4	4
NFKBIA	0.012	0.012	-9999	-10000	0	0
BIRC3	0.027	0.061	-9999	-0.4	10	10
CYCS	0.035	0.036	-9999	-0.25	4	4
RIPK1	0.011	0	-9999	-10000	0	0
CD247	0.01	0.036	-9999	-0.41	3	3
MAP2K7	0.037	0.034	-9999	-0.36	1	1
protein ubiquitination	0.049	0.026	-9999	-0.18	2	2
CRADD	0.011	0	-9999	-10000	0	0
DAXX	0.011	0	-9999	-10000	0	0
FAS	0.007	0.04	-9999	-0.41	5	5
BID	0.031	0.038	-9999	-0.26	4	4
NF-kappa-B/RelA/I kappa B alpha	0.027	0.035	-9999	-0.22	9	9
TRADD	0.011	0	-9999	-10000	0	0
MAP3K5	0.009	0.031	-9999	-0.41	3	3
CFLAR	0.011	0	-9999	-10000	0	0
FADD	0.011	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.027	0.035	-9999	-0.22	9	9
MAPK8	0.039	0.038	-9999	-0.34	1	1
APAF1	0.011	0	-9999	-10000	0	0
TRAF1	0.011	0	-9999	-10000	0	0
TRAF2	0.011	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.026	0.04	-9999	-0.28	4	4
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.044	0.03	-9999	-0.24	2	2
CHUK	0.05	0.028	-9999	-0.2	2	2
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.03	0.026	-9999	-10000	0	0
TCRz/NEF	0.01	0.039	-9999	-0.22	14	14
TNF	-0.032	0.11	-9999	-0.33	67	67
FASLG	0.013	0.061	-9999	-0.35	13	13
NFKB1	0.011	0.022	-9999	-0.4	1	1
TNFR1A/BAG4/TNF-alpha	-0.003	0.067	-9999	-0.18	70	70
CASP6	-0.003	0.022	-9999	-10000	0	0
CASP7	0.057	0.068	-9999	-0.42	9	9
RELA	0.012	0.012	-9999	-10000	0	0
CASP2	0.011	0	-9999	-10000	0	0
CASP3	0.057	0.068	-9999	-0.42	9	9
TNFRSF1A	0.011	0	-9999	-10000	0	0
TNFR1A/BAG4	0.015	0.022	-9999	-0.28	3	3
CASP8	0.011	0	-9999	-10000	0	0
CASP9	0.011	0	-9999	-10000	0	0
MAP3K14	0.047	0.029	-9999	-0.22	2	2
APAF-1/Caspase 9	-0.007	0.04	-9999	-0.28	9	9
BCL2	0.026	0.067	-9999	-0.29	6	6

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	0.024	0.013	-10000	0	-0.19	2	2
epithelial cell differentiation	-0.001	0.011	-10000	0	-0.18	2	2
CYFIP2	0.009	0.031	-10000	0	-0.41	3	3
ENAH	0.048	0.018	-10000	0	-10000	0	0
EGFR	0	0.066	-10000	0	-0.4	14	14
EPHA2	0.011	0	-10000	0	-10000	0	0
MYO6	0.029	0.012	-10000	0	-10000	0	0
CTNNB1	0.011	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.021	0.019	-10000	0	-0.23	3	3
AQP5	0.013	0.048	-10000	0	-0.38	7	7
CTNND1	0.011	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.029	0.012	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.023	0.038	-10000	0	-0.36	1	1
EGF	-0.005	0.07	-10000	0	-0.34	23	23
NCKAP1	0.011	0	-10000	0	-10000	0	0
AQP3	-0.004	0.044	-10000	0	-0.45	5	5
cortical microtubule organization	-0.001	0.011	-10000	0	-0.18	2	2
GO:0000145	0.027	0.011	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.025	0.013	-10000	0	-0.18	2	2
MLLT4	0.011	0	-10000	0	-10000	0	0
ARF6/GDP	-0.001	0.013	-10000	0	-10000	0	0
ARF6	0.011	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.027	0.017	-10000	0	-0.2	2	2
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.037	0.012	-10000	0	-10000	0	0
PVRL2	0.011	0	-10000	0	-10000	0	0
ZYX	0.029	0.012	-10000	0	-10000	0	0
ARF6/GTP	0.03	0.016	-10000	0	-10000	0	0
CDH1	0.009	0.026	-10000	0	-0.41	2	2
EGFR/EGFR/EGF/EGF	-0.01	0.04	-10000	0	-0.32	3	3
RhoA/GDP	-0.001	0.01	-10000	0	-10000	0	0
actin cytoskeleton organization	0.033	0.012	-10000	0	-10000	0	0
IGF-1R heterotetramer	-0.005	0.081	-10000	0	-0.41	21	21
GIT1	0.011	0	-10000	0	-10000	0	0
IGF1R	-0.005	0.081	-10000	0	-0.41	21	21
IGF1	-0.068	0.16	-10000	0	-0.41	101	101
DIAPH1	-0.003	0.039	-10000	0	-0.52	3	3
Wnt receptor signaling pathway	0.001	0.011	0.18	2	-10000	0	2
RHOA	0.011	0	-10000	0	-10000	0	0
RhoA/GTP	-0.001	0.013	-10000	0	-10000	0	0
CTNNA1	0.011	0	-10000	0	-10000	0	0
VCL	0.033	0.012	-10000	0	-10000	0	0
EFNA1	0.01	0.021	-10000	0	-0.33	2	2
LPP	0.034	0.012	-10000	0	-10000	0	0
Ephrin A1/EPHA2	-0.001	0.012	-10000	0	-10000	0	0
SEC6/SEC8	-0.001	0.009	-10000	0	-10000	0	0
MGAT3	0.023	0.038	-10000	0	-0.36	1	1
HGF/MET	-0.036	0.073	-10000	0	-0.47	3	3
HGF	-0.075	0.17	-10000	0	-0.41	110	110
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.024	0.013	-10000	0	-0.2	2	2
actin cable formation	0.062	0.017	-10000	0	-10000	0	0
KIAA1543	0.033	0.025	-10000	0	-0.35	2	2
KIFC3	0.029	0.012	-10000	0	-10000	0	0
NCK1	0.009	0.026	-10000	0	-0.41	2	2
EXOC3	0.011	0	-10000	0	-10000	0	0
ACTN1	0.029	0.012	-10000	0	-10000	0	0
NCK1/GIT1	0.015	0.018	-10000	0	-0.28	2	2
mol:GDP	-0.001	0.011	-10000	0	-0.18	2	2
EXOC4	0.011	0	-10000	0	-10000	0	0
STX4	0.029	0.012	-10000	0	-10000	0	0
PIP5K1C	0.029	0.012	-10000	0	-10000	0	0
LIMA1	0.011	0	-10000	0	-10000	0	0
ABI1	0.011	0	-10000	0	-10000	0	0
ROCK1	0.047	0.016	-10000	0	-10000	0	0
adherens junction assembly	0.045	0.027	-10000	0	-0.36	2	2
IGF-1R heterotetramer/IGF1	-0.038	0.078	-10000	0	-0.35	12	12
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.016	0	-10000	0	-10000	0	0
MET	0.005	0.046	-10000	0	-0.37	8	8
PLEKHA7	0.029	0.015	-10000	0	-10000	0	0
mol:GTP	0.026	0.017	-10000	0	-0.2	2	2
establishment of epithelial cell apical/basal polarity	0.047	0.011	-10000	0	-10000	0	0
cortical actin cytoskeleton stabilization	0.024	0.013	-10000	0	-0.19	2	2
regulation of cell-cell adhesion	0.033	0.012	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.024	0.013	-10000	0	-0.2	2	2

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.014	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.058	0.035	-9999	-10000	0	0
ERC1	0.011	0	-9999	-10000	0	0
RIP2/NOD2	0.015	0.016	-9999	-0.25	2	2
NFKBIA	0.036	0.01	-9999	-10000	0	0
BIRC2	0.011	0	-9999	-10000	0	0
IKBKB	0.011	0	-9999	-10000	0	0
RIPK2	0.011	0	-9999	-10000	0	0
IKBKG	0.037	0.009	-9999	-10000	0	0
IKK complex/A20	-0.012	0.032	-9999	-10000	0	0
NEMO/A20/RIP2	0.011	0	-9999	-10000	0	0
XPO1	0.011	0	-9999	-10000	0	0
NEMO/ATM	0.041	0.008	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.011	0	-9999	-10000	0	0
Exportin 1/RanGTP	0.015	0	-9999	-10000	0	0
IKK complex/ELKS	0	0.005	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0.022	0	-9999	-10000	0	0
NOD2	0.01	0.023	-9999	-0.37	2	2
NFKB1	0.013	0.018	-9999	-0.4	1	1
RELA	0.014	0	-9999	-10000	0	0
MALT1	0.011	0	-9999	-10000	0	0
cIAP1/UbcH5C	0.016	0	-9999	-10000	0	0
ATM	0.011	0	-9999	-10000	0	0
TNF/TNFR1A	-0.013	0.078	-9999	-0.22	67	67
TRAF6	0.011	0	-9999	-10000	0	0
PRKCA	-0.017	0.1	-9999	-0.41	36	36
CHUK	0.011	0	-9999	-10000	0	0
UBE2D3	0.011	0	-9999	-10000	0	0
TNF	-0.032	0.11	-9999	-0.33	67	67
NF kappa B1 p50/RelA	0.031	0.011	-9999	-0.22	1	1
BCL10	0.011	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.035	0.01	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.014	0	-9999	-10000	0	0
TNFRSF1A	0.011	0	-9999	-10000	0	0
IKK complex	0.046	0.008	-9999	-10000	0	0
CYLD	0.011	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.009	0.035	-9999	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.01	0.018	-9999	-0.41	1	1
PLK4	0.008	0.033	-9999	-0.33	5	5
regulation of centriole replication	0.015	0.026	-9999	-0.23	6	6

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.007	0.04	-10000	0	-0.37	6	6
positive regulation of NF-kappaB transcription factor activity	0.006	0.053	-10000	0	-0.27	19	19
MAP2K4	0.035	0.02	-10000	0	-10000	0	0
IKBKB	0.011	0	-10000	0	-10000	0	0
TNFRSF10B	0.011	0	-10000	0	-10000	0	0
TNFRSF10A	0.009	0.026	-10000	0	-0.41	2	2
SMPD1	0.014	0.015	-10000	0	-0.16	3	3
IKBKG	0.011	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.001	0.065	-10000	0	-0.41	13	13
TRAIL/TRAILR2	0.013	0.028	-10000	0	-0.25	6	6
TRAIL/TRAILR3	0.013	0.031	-10000	0	-0.25	7	7
TRAIL/TRAILR1	0.012	0.033	-10000	0	-0.26	8	8
TRAIL/TRAILR4	0.006	0.053	-10000	0	-0.27	19	19
TRAIL/TRAILR1/DAP3/GTP	0.018	0.025	-10000	0	-0.19	8	8
IKK complex	-0.001	0.007	-10000	0	-10000	0	0
RIPK1	0.011	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.008	0	-10000	0	-10000	0	0
MAPK3	0.015	0.028	-10000	0	-0.25	6	6
MAP3K1	0.031	0.019	-10000	0	-0.2	3	3
TRAILR4 (trimer)	0.001	0.064	-10000	0	-0.41	13	13
TRADD	0.011	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.009	0.026	-10000	0	-0.41	2	2
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.028	0.022	-10000	0	-0.19	5	5
CFLAR	0.011	0	-10000	0	-10000	0	0
MAPK1	0.015	0.028	-10000	0	-0.25	6	6
TRAIL/TRAILR1/FADD/TRADD/RIP	0.03	0.024	-10000	0	-10000	0	0
mol:ceramide	0.014	0.015	-10000	0	-0.16	3	3
FADD	0.011	0	-10000	0	-10000	0	0
MAPK8	0.037	0.028	-10000	0	-10000	0	0
TRAF2	0.011	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.01	0.018	-10000	0	-0.41	1	1
CHUK	0.011	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	0.019	0.028	-10000	0	-0.21	8	8
DAP3	0.011	0	-10000	0	-10000	0	0
CASP10	0.002	0.046	0.22	13	-0.31	4	17
JNK cascade	0.006	0.053	-10000	0	-0.27	19	19
TRAIL (trimer)	0.007	0.04	-10000	0	-0.37	6	6
TNFRSF10C	0.01	0.018	-10000	0	-0.41	1	1
TRAIL/TRAILR1/DAP3/GTP/FADD	0.023	0.024	-10000	0	-0.18	5	5
TRAIL/TRAILR2/FADD	0.02	0.024	-10000	0	-0.2	6	6
cell death	0.014	0.015	-10000	0	-0.16	3	3
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.028	0.017	-10000	0	-0.19	3	3
TRAILR2 (trimer)	0.011	0	-10000	0	-10000	0	0
CASP8	0.001	0.009	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.031	0.02	-10000	0	-10000	0	0

×

Class I PI3K signaling events

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
ARF5/GTP	0.002	0.023	0.21	6	-10000	0	6
DAPP1	0.028	0.043	-10000	0	-0.3	3	3
Src family/SYK family/BLNK-LAT/BTK-ITK	0.044	0.047	-10000	0	-0.49	1	1
mol:DAG	0.046	0.031	0.16	5	-0.18	1	6
HRAS	0.012	0.001	-10000	0	-10000	0	0
RAP1A	0.012	0.001	-10000	0	-10000	0	0
ARF5/GDP	0.027	0.046	-10000	0	-0.32	3	3
PLCG2	0.01	0.023	-10000	0	-0.37	2	2
PLCG1	0.011	0	-10000	0	-10000	0	0
ARF5	0.011	0	-10000	0	-10000	0	0
mol:GTP	0.002	0.023	0.2	6	-10000	0	6
ARF1/GTP	0.002	0.023	0.21	6	-10000	0	6
RHOA	0.011	0	-10000	0	-10000	0	0
YES1	0.011	0	-10000	0	-10000	0	0
RAP1A/GTP	0.023	0.021	0.2	6	-10000	0	6
ADAP1	0.002	0.022	0.2	6	-10000	0	6
ARAP3	0.002	0.023	0.2	6	-10000	0	6
INPPL1	0.011	0	-10000	0	-10000	0	0
PREX1	0.011	0	-10000	0	-10000	0	0
ARHGEF6	0	0.067	-10000	0	-0.41	14	14
ARHGEF7	0.011	0	-10000	0	-10000	0	0
ARF1	0.011	0	-10000	0	-10000	0	0
NRAS	0.012	0.001	-10000	0	-10000	0	0
FYN	0.011	0	-10000	0	-10000	0	0
ARF6	0.011	0	-10000	0	-10000	0	0
FGR	0.002	0.062	-10000	0	-0.41	12	12
mol:Ca2+	0.032	0.018	-10000	0	-10000	0	0
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0	0.067	-10000	0	-0.41	14	14
ZAP70	-0.001	0.063	-10000	0	-0.34	18	18
mol:IP3	0.039	0.024	-10000	0	-10000	0	0
LYN	0.011	0	-10000	0	-10000	0	0
ARF1/GDP	0.027	0.046	-10000	0	-0.32	3	3
RhoA/GDP	0	0.025	0.2	5	-0.2	1	6
PDK1/Src/Hsp90	0.022	0	-10000	0	-10000	0	0
BLNK	0.009	0.029	-10000	0	-0.38	3	3
actin cytoskeleton reorganization	0.046	0.036	0.2	5	-0.23	3	8
SRC	0.011	0	-10000	0	-10000	0	0
PLEKHA2	0.023	0.011	-10000	0	-0.23	1	1
RAC1	0.011	0	-10000	0	-10000	0	0
PTEN	0.003	0.041	-10000	0	-0.38	6	6
HSP90AA1	0.011	0	-10000	0	-10000	0	0
ARF6/GTP	0.002	0.023	0.21	6	-10000	0	6
RhoA/GTP	0.028	0.02	0.2	6	-10000	0	6
Src family/SYK family/BLNK-LAT	0.034	0.04	-10000	0	-0.3	1	1
BLK	-0.015	0.087	-10000	0	-0.33	38	38
PDPK1	0.011	0	-10000	0	-10000	0	0
CYTH1	0.002	0.022	0.2	6	-10000	0	6
HCK	0.007	0.039	-10000	0	-0.33	7	7
CYTH3	0.002	0.022	0.2	6	-10000	0	6
CYTH2	0.002	0.022	0.2	6	-10000	0	6
KRAS	0.011	0.015	-10000	0	-0.33	1	1
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.035	0.029	-10000	0	-0.38	2	2
SGK1	0	0.031	0.16	6	-0.42	2	8
INPP5D	0.01	0.018	-10000	0	-0.41	1	1
mol:GDP	0.021	0.048	-10000	0	-0.22	13	13
SOS1	0.011	0	-10000	0	-10000	0	0
SYK	0.01	0.015	-10000	0	-0.33	1	1
ARF6/GDP	0	0.026	0.2	6	-0.2	1	7
mol:PI-3-4-5-P3	0.002	0.026	0.23	6	-10000	0	6
ARAP3/RAP1A/GTP	0.023	0.021	0.2	6	-10000	0	6
VAV1	0.007	0.037	-10000	0	-0.34	6	6
mol:PI-3-4-P2	0.018	0.013	-10000	0	-0.28	1	1
RAS family/GTP/PI3K Class I	0.025	0.01	-10000	0	-10000	0	0
PLEKHA1	0.023	0.011	-10000	0	-0.23	1	1
Rac1/GDP	0.027	0.046	-10000	0	-0.32	3	3
LAT	0.011	0	-10000	0	-10000	0	0
Rac1/GTP	0.019	0.068	-10000	0	-0.26	25	25
ITK	-0.002	0.035	0.2	6	-10000	0	6
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.053	0.039	0.18	5	-0.24	1	6
LCK	0.008	0.034	-10000	0	-0.35	5	5
BTK	0.001	0.025	0.2	6	-10000	0	6

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.19	0.21	-10000	0	-0.41	261	261
CLTC	0.026	0.001	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.021	0.006	-10000	0	-10000	0	0
Dynamin 2/GTP	0.02	0	-10000	0	-10000	0	0
EXOC4	0.011	0	-10000	0	-10000	0	0
CD59	0.023	0.001	-10000	0	-10000	0	0
CPE	-0.009	0.074	-10000	0	-0.23	53	53
CTNNB1	0.011	0	-10000	0	-10000	0	0
membrane fusion	0.021	0.006	-10000	0	-10000	0	0
CTNND1	0.025	0	-10000	0	-10000	0	0
DNM2	0.011	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.026	0.003	-10000	0	-10000	0	0
TSHR	0.005	0.041	-10000	0	-0.19	23	23
INS	0.01	0.002	-10000	0	-10000	0	0
BIN1	0.008	0.036	-10000	0	-0.41	4	4
mol:Choline	0.021	0.006	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.015	0	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.011	0	-10000	0	-10000	0	0
mol:Ca2+	0.02	0	-10000	0	-10000	0	0
JUP	0.023	0.008	-10000	0	-10000	0	0
ASAP2/amphiphysin II	0.02	0.019	-10000	0	-0.2	4	4
ARF6/GTP	0.008	0	-10000	0	-10000	0	0
CDH1	0.022	0.011	-10000	0	-10000	0	0
clathrin-independent pinocytosis	0.008	0	-10000	0	-10000	0	0
MAPK8IP3	0.011	0	-10000	0	-10000	0	0
positive regulation of endocytosis	0.008	0	-10000	0	-10000	0	0
EXOC2	0.011	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.035	0	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.011	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0	0.006	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.015	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.015	0	-10000	0	-10000	0	0
ACAP1	0.02	0.009	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.018	0.012	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.03	0.004	-10000	0	-10000	0	0
JIP4/KLC1	0.021	0	-10000	0	-10000	0	0
EXOC1	0.011	0	-10000	0	-10000	0	0
exocyst	0.035	0	-10000	0	-10000	0	0
RALA/GTP	0.008	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.015	0	-10000	0	-10000	0	0
receptor recycling	0.008	0	-10000	0	-10000	0	0
CTNNA1	0.025	0	-10000	0	-10000	0	0
NME1	0.015	0	-10000	0	-10000	0	0
clathrin coat assembly	0.026	0.002	-10000	0	-10000	0	0
IL2RA	0.02	0.016	-10000	0	-10000	0	0
VAMP3	0.015	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.074	0.076	-10000	0	-10000	0	0
EXOC6	0.011	0	-10000	0	-10000	0	0
PLD1	0.018	0	-10000	0	-10000	0	0
PLD2	0.017	0.011	-10000	0	-0.24	1	1
EXOC5	0.011	0	-10000	0	-10000	0	0
PIP5K1C	0.026	0.001	-10000	0	-10000	0	0
SDC1	0.003	0.032	-10000	0	-10000	0	0
ARF6/GDP	0.015	0	-10000	0	-10000	0	0
EXOC7	0.011	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	0	0.006	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.021	0.006	-10000	0	-10000	0	0
endocytosis	-0.019	0.019	0.2	4	-10000	0	4
SCAMP2	0.011	0	-10000	0	-10000	0	0
ADRB2	-0.004	0.075	-10000	0	-10000	0	0
EXOC3	0.011	0	-10000	0	-10000	0	0
ASAP2	0.011	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.021	0	-10000	0	-10000	0	0
KLC1	0.011	0	-10000	0	-10000	0	0
AVPR2	-0.031	0.091	-10000	0	-0.21	1	1
RALA	0.011	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0	0.005	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.012	0.032	-9999	-0.24	2	2
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.027	0.032	-9999	-0.24	2	2
SUMO1	0.011	0	-9999	-10000	0	0
ZFPM1	0.009	0.026	-9999	-0.41	2	2
NPC/RanGAP1/SUMO1/Ubc9	0.017	0	-9999	-10000	0	0
FKBP3	0.011	0	-9999	-10000	0	0
Histones	0.028	0.025	-9999	-10000	0	0
YY1/LSF	0.018	0.041	-9999	-0.2	18	18
SMG5	0.011	0	-9999	-10000	0	0
RAN	0.011	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	0.015	0.035	-9999	-0.19	2	2
I kappa B alpha/HDAC1	0.016	0.028	-9999	-10000	0	0
SAP18	0.011	0	-9999	-10000	0	0
RELA	0.02	0.031	-9999	-0.19	4	4
HDAC1/Smad7	0.022	0.015	-9999	-0.23	2	2
RANGAP1	0.011	0	-9999	-10000	0	0
HDAC3/TR2	0.016	0.028	-9999	-10000	0	0
NuRD/MBD3 Complex	0.037	0.013	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.023	0.03	-9999	-0.18	1	1
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.029	0.12	-9999	-0.41	51	51
GATA1	0.006	0.005	-9999	-10000	0	0
Mad/Max	0.016	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.044	0.017	-9999	-10000	0	0
RBBP7	0.011	0	-9999	-10000	0	0
NPC	0.007	0	-9999	-10000	0	0
RBBP4	0.009	0.031	-9999	-0.41	3	3
MAX	0.011	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.011	0	-9999	-10000	0	0
NFKBIA	0.012	0.031	-9999	-10000	0	0
KAT2B	0.004	0.054	-9999	-0.41	9	9
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.034	0.014	-9999	-10000	0	0
SIN3 complex	0.028	0	-9999	-10000	0	0
SMURF1	0.011	0	-9999	-10000	0	0
CHD3	0.011	0	-9999	-10000	0	0
SAP30	0.011	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.011	0	-9999	-10000	0	0
YY1/HDAC3	0.022	0.036	-9999	-10000	0	0
YY1/HDAC2	0.021	0.031	-9999	-0.19	11	11
YY1/HDAC1	0.021	0.031	-9999	-0.19	11	11
NuRD/MBD2 Complex (MeCP1)	0.037	0.013	-9999	-10000	0	0
PPARG	0.005	0.071	-9999	-0.26	31	31
HDAC8/hEST1B	0.022	0	-9999	-10000	0	0
UBE2I	0.011	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.011	0	-9999	-10000	0	0
TNFRSF1A	0.011	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.016	0.028	-9999	-10000	0	0
MBD3L2	0.002	0.004	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.021	0.015	-9999	-0.23	2	2
CREBBP	0.009	0.026	-9999	-0.41	2	2
NuRD/MBD3/MBD3L2 Complex	0.041	0.013	-9999	-10000	0	0
HDAC1	0.011	0	-9999	-10000	0	0
HDAC3	0.012	0.031	-9999	-10000	0	0
HDAC2	0.011	0	-9999	-10000	0	0
YY1	0.019	0.036	-9999	-0.23	11	11
HDAC8	0.011	0	-9999	-10000	0	0
SMAD7	0.009	0.026	-9999	-0.41	2	2
NCOR2	0.011	0	-9999	-10000	0	0
MXD1	0.011	0	-9999	-10000	0	0
STAT3	0.02	0.018	-9999	-0.27	2	2
NFKB1	0.01	0.018	-9999	-0.41	1	1
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.011	0	-9999	-10000	0	0
YY1/LSF/HDAC1	0.024	0.037	-9999	-0.19	7	7
YY1/SAP30/HDAC1	0.026	0.028	-9999	-10000	0	0
EP300	0.011	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.02	0.018	-9999	-0.27	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.012	0.031	-9999	-10000	0	0
histone deacetylation	0.037	0.013	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.023	0.028	-9999	-10000	0	0
nuclear export	-0.022	0	-9999	-10000	0	0
PRKACA	0.011	0	-9999	-10000	0	0
GATAD2B	0.011	0	-9999	-10000	0	0
GATAD2A	0.011	0	-9999	-10000	0	0
GATA2/HDAC3	-0.004	0.073	-9999	-0.21	51	51
GATA1/HDAC1	0.013	0.004	-9999	-10000	0	0
GATA1/HDAC3	0.005	0.027	-9999	-10000	0	0
CHD4	0.011	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.013	0.078	-9999	-0.22	67	67
SIN3/HDAC complex/Mad/Max	0.037	0.013	-9999	-10000	0	0
NuRD Complex	0.044	0.013	-9999	-10000	0	0
positive regulation of chromatin silencing	0.027	0.025	-9999	-10000	0	0
SIN3B	0.011	0	-9999	-10000	0	0
MTA2	0.011	0	-9999	-10000	0	0
SIN3A	0.011	0	-9999	-10000	0	0
XPO1	0.011	0	-9999	-10000	0	0
SUMO1/HDAC1	0.025	0	-9999	-10000	0	0
HDAC complex	0.027	0.017	-9999	-0.2	3	3
GATA1/Fog1	0.012	0.018	-9999	-0.28	2	2
FKBP25/HDAC1/HDAC2	0.022	0	-9999	-10000	0	0
TNF	-0.032	0.11	-9999	-0.33	67	67
negative regulation of cell growth	0.037	0.013	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.037	0.013	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.027	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.023	0.032	-9999	-0.25	2	2
SIN3/HDAC complex/NCoR1	0.035	0.015	-9999	-10000	0	0
TFCP2	0.006	0.048	-9999	-0.41	7	7
NR2C1	0.011	0	-9999	-10000	0	0
MBD3	0.011	0	-9999	-10000	0	0
MBD2	0.011	0	-9999	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.011	0	-10000	0	-10000	0	0
Rac1/GDP	0	0.003	-10000	0	-10000	0	0
DOCK1	0.006	0.048	-10000	0	-0.41	7	7
ITGA4	0.009	0.029	-10000	0	-0.38	3	3
RAC1	0.011	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	0.014	0.023	-10000	0	-0.25	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.011	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.021	0.017	-10000	0	-0.21	3	3
alpha4/beta7 Integrin/Paxillin	0.026	0.017	-10000	0	-0.2	2	2
lamellipodium assembly	-0.006	0.047	-10000	0	-0.4	6	6
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
PI3K	0.013	0.031	-10000	0	-0.28	6	6
ARF6	0.011	0	-10000	0	-10000	0	0
TLN1	0.011	0	-10000	0	-10000	0	0
PXN	0.018	0	-10000	0	-10000	0	0
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
ARF6/GTP	-0.001	0.011	-10000	0	-10000	0	0
cell adhesion	0.031	0.015	-10000	0	-0.18	2	2
CRKL/CBL	0.016	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.026	0.016	-10000	0	-0.2	2	2
ITGB1	0.011	0	-10000	0	-10000	0	0
ITGB7	0.01	0.015	-10000	0	-0.33	1	1
ARF6/GDP	0	0.003	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.016	0.06	-10000	0	-0.19	40	40
p130Cas/Crk/Dock1	0.019	0.028	-10000	0	-0.23	7	7
VCAM1	-0.02	0.11	-10000	0	-0.41	40	40
alpha4/beta1 Integrin/Paxillin/Talin	0.032	0.015	-10000	0	-0.18	2	2
alpha4/beta1 Integrin/Paxillin/GIT1	0.032	0.015	-10000	0	-0.18	2	2
BCAR1	0.011	0	-10000	0	-10000	0	0
mol:GDP	-0.031	0.015	0.18	2	-10000	0	2
CBL	0.011	0	-10000	0	-10000	0	0
PRKACA	0.011	0	-10000	0	-10000	0	0
GIT1	0.011	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.032	0.015	-10000	0	-0.18	2	2
Rac1/GTP	-0.007	0.053	-10000	0	-0.44	6	6

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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
SMAD4	0.01	0.018	-9999	-0.41	1	1
SMAD2	0.011	0	-9999	-10000	0	0
SMAD3	0.031	0.017	-9999	-10000	0	0
SMAD3/SMAD4	0.036	0.019	-9999	-0.33	1	1
SMAD4/Ubc9/PIASy	0.022	0.011	-9999	-0.23	1	1
SMAD2/SMAD2/SMAD4	0.025	0.033	-9999	-10000	0	0
PPM1A	0.011	0	-9999	-10000	0	0
CALM1	0.011	0	-9999	-10000	0	0
SMAD2/SMAD4	0.017	0.009	-9999	-0.2	1	1
MAP3K1	0.011	0	-9999	-10000	0	0
TRAP-1/SMAD4	0.011	0.038	-9999	-0.28	9	9
MAPK3	0.011	0	-9999	-10000	0	0
MAPK1	0.011	0	-9999	-10000	0	0
NUP214	0.011	0	-9999	-10000	0	0
CTDSP1	0.011	0	-9999	-10000	0	0
CTDSP2	0.011	0	-9999	-10000	0	0
CTDSPL	0.011	0	-9999	-10000	0	0
KPNB1	0.011	0	-9999	-10000	0	0
TGFBRAP1	0.005	0.051	-9999	-0.41	8	8
UBE2I	0.011	0	-9999	-10000	0	0
NUP153	0.01	0.018	-9999	-0.41	1	1
KPNA2	-0.004	0.07	-9999	-0.33	24	24
PIAS4	0.011	0	-9999	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.011	0	-9999	-10000	0	0
ITGB7	0.01	0.015	-9999	-0.33	1	1
ITGA4	0.009	0.029	-9999	-0.38	3	3
alpha4/beta7 Integrin	0.014	0.023	-9999	-0.25	4	4
alpha4/beta1 Integrin	0.015	0.021	-9999	-0.26	3	3

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.027	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP1	0.018	0	-9999	-10000	0	0
mol:DAG	0.031	0.008	-9999	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	0.024	0	-9999	-10000	0	0
CaM/Ca2+	0.036	0.007	-9999	-10000	0	0
HIF1A	0.018	0	-9999	-10000	0	0
GAB1	0.008	0.036	-9999	-0.41	4	4
AKT1	0.043	0.026	-9999	-10000	0	0
PLCG1	0.031	0.008	-9999	-10000	0	0
NOS3	0.048	0.017	-9999	-10000	0	0
CBL	0.011	0	-9999	-10000	0	0
mol:NO	0.048	0.017	-9999	-10000	0	0
FLT1	0.025	0	-9999	-10000	0	0
PGF	0.01	0.015	-9999	-0.33	1	1
VEGFR1 homodimer/NRP2/VEGFR121	0.021	0.047	-9999	-10000	0	0
CALM1	0.011	0	-9999	-10000	0	0
PIK3CA	0.01	0.018	-9999	-0.41	1	1
eNOS/Hsp90	0.052	0.016	-9999	-10000	0	0
endothelial cell proliferation	0.019	0.065	-9999	-0.31	4	4
mol:Ca2+	0.031	0.007	-9999	-10000	0	0
MAPK3	0.026	0.051	-9999	-10000	0	0
MAPK1	0.026	0.051	-9999	-10000	0	0
PIK3R1	0.007	0.04	-9999	-0.41	5	5
PLGF homodimer	0.01	0.015	-9999	-0.33	1	1
PRKACA	0.011	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.062	0.16	-9999	-0.41	94	94
VEGFA homodimer	0.011	0	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0.027	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.03	0.049	-9999	-10000	0	0
PI3K	0.035	0.023	-9999	-10000	0	0
PRKCA	0.021	0.053	-9999	-10000	0	0
PRKCB	0.023	0.051	-9999	-10000	0	0
VEGFR1 homodimer/PLGF homodimer	0.026	0.008	-9999	-10000	0	0
VEGFA	0.011	0	-9999	-10000	0	0
VEGFB	0.011	0	-9999	-10000	0	0
mol:IP3	0.031	0.008	-9999	-10000	0	0
RASA1	0.03	0.022	-9999	-10000	0	0
NRP2	-0.009	0.089	-9999	-0.41	25	25
VEGFR1 homodimer	0.025	0	-9999	-10000	0	0
VEGFB homodimer	0.011	0	-9999	-10000	0	0
NCK1	0.009	0.026	-9999	-0.41	2	2
eNOS/Caveolin-1	0.02	0.074	-9999	-0.41	1	1
PTPN11	0.011	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.033	0.023	-9999	-10000	0	0
mol:L-citrulline	0.048	0.017	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.037	0	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.031	0.014	-9999	-10000	0	0
CD2AP	0.011	0	-9999	-10000	0	0
PI3K/GAB1	0.037	0.028	-9999	-10000	0	0
PDPK1	0.037	0.022	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.032	0	-9999	-10000	0	0
mol:NADP	0.048	0.017	-9999	-10000	0	0
HSP90AA1	0.011	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.036	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP2	0.015	0.052	-9999	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.033	0.013	-10000	0	-10000	0	0
regulation of axonogenesis	-0.023	0.008	-10000	0	-10000	0	0
myoblast fusion	-0.017	0.013	-10000	0	-10000	0	0
mol:GTP	0.009	0.006	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.023	0.039	0.21	14	-10000	0	14
ARF1/GTP	0	0.002	-10000	0	-10000	0	0
mol:GM1	0.008	0.005	-10000	0	-10000	0	0
mol:Choline	0.022	0.011	-10000	0	-0.22	1	1
lamellipodium assembly	0.001	0.012	-10000	0	-10000	0	0
MAPK3	0.023	0.008	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.023	0.039	-10000	0	-0.22	14	14
ARF1	0.011	0	-10000	0	-10000	0	0
ARF6/GDP	0.017	0.013	-10000	0	-10000	0	0
ARF1/GDP	0.023	0.012	-10000	0	-10000	0	0
ARF6	0.01	0.003	-10000	0	-10000	0	0
RAB11A	0.011	0	-10000	0	-10000	0	0
TIAM1	0.002	0.067	-10000	0	-0.41	14	14
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.023	0.008	-10000	0	-10000	0	0
actin filament bundle formation	-0.021	0.01	-10000	0	-10000	0	0
KALRN	-0.001	0.023	-10000	0	-0.21	5	5
RAB11FIP3/RAB11A	0.016	0	-10000	0	-10000	0	0
RhoA/GDP	0.021	0.01	-10000	0	-10000	0	0
NME1	0.012	0.001	-10000	0	-10000	0	0
Rac1/GDP	0.021	0.01	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.009	0.006	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	0.001	0.012	-10000	0	-10000	0	0
RAC1	0.011	0	-10000	0	-10000	0	0
liver development	0.009	0.006	-10000	0	-10000	0	0
ARF6/GTP	0.009	0.006	-10000	0	-10000	0	0
RhoA/GTP	0	0.002	-10000	0	-10000	0	0
mol:GDP	0.002	0.013	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	0.022	0.005	-10000	0	-10000	0	0
RHOA	0.011	0	-10000	0	-10000	0	0
PLD1	0.017	0.004	-10000	0	-10000	0	0
RAB11FIP3	0.011	0	-10000	0	-10000	0	0
tube morphogenesis	0.001	0.012	-10000	0	-10000	0	0
ruffle organization	0.023	0.008	-10000	0	-10000	0	0
regulation of epithelial cell migration	0.009	0.006	-10000	0	-10000	0	0
PLD2	0.017	0.013	-10000	0	-0.26	1	1
PIP5K1A	0.023	0.008	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.022	0.011	-10000	0	-0.22	1	1
Rac1/GTP	0.001	0.012	-10000	0	-10000	0	0

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.016	0.01	-9999	-0.22	1	1
FBXW11	0.011	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.021	0.011	-9999	-0.23	1	1
NF kappa B1 p50/RelA/I kappa B alpha	0.037	0.012	-9999	-10000	0	0
NFKBIA	0.023	0.01	-9999	-0.17	1	1
MAPK14	0.011	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.021	0.011	-9999	-0.23	1	1
ARRB2	0.014	0	-9999	-10000	0	0
REL	0.011	0.001	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.021	0.014	-9999	-0.2	2	2
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.021	0.011	-9999	-0.23	1	1
PIK3CA	0.01	0.018	-9999	-0.41	1	1
NF kappa B1 p50 dimer	0.016	0.013	-9999	-0.28	1	1
PIK3R1	0.007	0.04	-9999	-0.41	5	5
NFKB1	0.018	0.013	-9999	-0.28	1	1
RELA	0.011	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.028	0.012	-9999	-0.18	1	1
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.04	0.012	-9999	-10000	0	0
SRC	0.011	0	-9999	-10000	0	0
PI3K	0.013	0.031	-9999	-0.28	6	6
NF kappa B1 p50/RelA	0.028	0.012	-9999	-0.18	1	1
IKBKB	0.011	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.011	0	-9999	-10000	0	0
SYK	0.01	0.015	-9999	-0.33	1	1
I kappa B alpha/PIK3R1	0.025	0.022	-9999	-0.18	5	5
cell death	0.039	0.012	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	0.021	0.011	-9999	-0.23	1	1
LCK	0.008	0.034	-9999	-0.35	5	5
BCL3	0.01	0.015	-9999	-0.33	1	1

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	0.032	0.025	-9999	-0.38	2	2
KLHL20	-0.002	0.013	-9999	-10000	0	0
CYFIP2	0.009	0.031	-9999	-0.41	3	3
Rac1/GDP	0.048	0.016	-9999	-0.21	2	2
ENAH	0.032	0.028	-9999	-0.38	2	2
AP1M1	0.011	0	-9999	-10000	0	0
RAP1B	0.011	0	-9999	-10000	0	0
RAP1A	0.011	0	-9999	-10000	0	0
CTNNB1	0.011	0	-9999	-10000	0	0
CDC42/GTP	0	0.008	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.002	0.011	-9999	-0.13	1	1
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.027	0.016	-9999	-0.2	2	2
RAPGEF1	0.041	0.022	-9999	-0.32	2	2
CTNND1	0.011	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.027	0.026	-9999	-0.4	2	2
CRK	0.037	0.024	-9999	-0.35	2	2
E-cadherin/gamma catenin/alpha catenin	0.021	0.023	-9999	-0.34	2	2
alphaE/beta7 Integrin	0.016	0.01	-9999	-0.22	1	1
IQGAP1	0.011	0	-9999	-10000	0	0
NCKAP1	0.011	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.021	0	-9999	-10000	0	0
DLG1	0.032	0.025	-9999	-0.38	2	2
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.01	-9999	-10000	0	0
MLLT4	0.011	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.016	0.036	-9999	-0.2	14	14
PI3K	-0.001	0.012	-9999	-10000	0	0
ARF6	0.011	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	0.015	0.027	-9999	-0.4	2	2
TIAM1	0	0.067	-9999	-0.41	14	14
E-cadherin(dimer)/Ca2+	0.026	0.013	-9999	-0.18	2	2
AKT1	-0.001	0.007	-9999	-10000	0	0
PIK3R1	0.007	0.04	-9999	-0.41	5	5
CDH1	0.009	0.026	-9999	-0.41	2	2
RhoA/GDP	0.048	0.016	-9999	-10000	0	0
actin cytoskeleton organization	0.034	0.016	-9999	-10000	0	0
CDC42/GDP	0.048	0.016	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.019	0.021	-9999	-0.31	2	2
ITGB7	0.01	0.015	-9999	-0.33	1	1
RAC1	0.011	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.028	0.014	-9999	-0.2	2	2
E-cadherin/Ca2+/beta catenin/alpha catenin	0.019	0.013	-9999	-0.19	2	2
mol:GDP	0.046	0.018	-9999	-0.24	2	2
CDC42/GTP/IQGAP1	0.015	0	-9999	-10000	0	0
JUP	0.01	0.018	-9999	-0.41	1	1
p120 catenin/RhoA/GDP	0.045	0.017	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0.015	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0.016	0	-9999	-10000	0	0
RHOA	0.011	0	-9999	-10000	0	0
CDC42	0.011	0	-9999	-10000	0	0
CTNNA1	0.011	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.026	0.015	-9999	-0.13	3	3
NME1	0.011	0	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.032	0.026	-9999	-0.38	2	2
regulation of cell-cell adhesion	0	0.007	-9999	-10000	0	0
WASF2	-0.001	0.006	-9999	-10000	0	0
Rap1/GTP	-0.001	0.009	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.031	0.021	-9999	-0.38	1	1
CCND1	0.031	0.018	-9999	-0.15	3	3
VAV2	0.041	0.024	-9999	-0.35	2	2
RAP1/GDP	0.043	0.015	-9999	-10000	0	0
adherens junction assembly	0.032	0.026	-9999	-0.37	2	2
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.011	0	-9999	-10000	0	0
PIP5K1C	0.011	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.036	0.02	-9999	-0.36	1	1
E-cadherin/beta catenin	-0.001	0.018	-9999	-0.3	2	2
mol:GTP	0	0	-9999	-10000	0	0
SRC	0.032	0.025	-9999	-0.38	2	2
PIK3CA	0.01	0.018	-9999	-0.41	1	1
Rac1/GTP	-0.003	0.019	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin	0.022	0.015	-9999	-0.23	2	2
ITGAE	0.011	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.027	0.026	-9999	-0.4	2	2

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.036	0.03	-10000	0	-0.22	7	7
adherens junction organization	0.033	0.028	-10000	0	-0.34	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.037	0.041	-10000	0	-0.38	2	2
FMN1	0.027	0.038	-10000	0	-0.34	2	2
mol:IP3	0.031	0.026	-10000	0	-0.29	1	1
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.028	0.027	-10000	0	-0.36	2	2
CTNNB1	0.011	0.001	-10000	0	-10000	0	0
AKT1	0.036	0.027	-10000	0	-0.33	1	1
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.033	0.028	-10000	0	-0.41	2	2
CTNND1	0.012	0.001	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.033	0.025	-10000	0	-0.47	1	1
VASP	0.033	0.025	-10000	0	-0.34	2	2
ZYX	0.033	0.025	-10000	0	-0.34	2	2
JUB	0.033	0.025	-10000	0	-0.34	2	2
EGFR(dimer)	0.028	0.045	-10000	0	-0.36	3	3
E-cadherin/beta catenin-gamma catenin	-0.001	0.02	-10000	0	-0.31	2	2
mol:PI-3-4-5-P3	0.03	0.028	-10000	0	-0.35	1	1
PIK3CA	0.011	0.018	-10000	0	-0.41	1	1
PI3K	0.031	0.028	-10000	0	-0.36	1	1
FYN	0.031	0.036	-10000	0	-0.24	1	1
mol:Ca2+	0.03	0.025	-10000	0	-0.29	1	1
JUP	0.01	0.018	-10000	0	-0.4	1	1
PIK3R1	0.008	0.04	-10000	0	-0.41	5	5
mol:DAG	0.031	0.026	-10000	0	-0.29	1	1
CDH1	0.009	0.025	-10000	0	-0.41	2	2
RhoA/GDP	0.037	0.041	-10000	0	-0.38	2	2
establishment of polarity of embryonic epithelium	0.033	0.025	-10000	0	-0.33	2	2
SRC	0.011	0	-10000	0	-10000	0	0
RAC1	0.011	0	-10000	0	-10000	0	0
RHOA	0.011	0	-10000	0	-10000	0	0
EGFR	0	0.066	-10000	0	-0.4	14	14
CASR	0.024	0.043	-10000	0	-0.27	1	1
RhoA/GTP	-0.002	0.019	-10000	0	-0.26	1	1
AKT2	0.036	0.027	-10000	0	-0.33	1	1
actin cable formation	0.032	0.037	-10000	0	-0.46	1	1
apoptosis	-0.034	0.028	0.2	7	-10000	0	7
CTNNA1	0.012	0.001	-10000	0	-10000	0	0
mol:GDP	0.032	0.043	-10000	0	-0.41	2	2
PIP5K1A	0.033	0.025	-10000	0	-0.48	1	1
PLCG1	0.031	0.026	-10000	0	-0.3	1	1
Rac1/GTP	-0.005	0.035	-10000	0	-0.41	2	2
homophilic cell adhesion	0.001	0.001	-10000	0	-10000	0	0

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.021	0.023	-9999	-0.34	2	2
E-cadherin/beta catenin	0.015	0.018	-9999	-0.28	2	2
CTNNB1	0.011	0	-9999	-10000	0	0
JUP	0.01	0.018	-9999	-0.41	1	1
CDH1	0.009	0.026	-9999	-0.41	2	2

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.039	0.011	-9999	-10000	0	0
CLOCK	0.014	0.001	-9999	-10000	0	0
TIMELESS/CRY2	0.034	0.011	-9999	-10000	0	0
DEC1/BMAL1	0.011	0.013	-9999	-0.28	1	1
ATR	0.011	0	-9999	-10000	0	0
NR1D1	0.033	0.009	-9999	-10000	0	0
ARNTL	0.013	0.018	-9999	-0.41	1	1
TIMELESS	0.033	0.013	-9999	-10000	0	0
NPAS2	0.01	0.04	-9999	-0.41	5	5
CRY2	0.011	0	-9999	-10000	0	0
mol:CO	-0.011	0.003	-9999	-10000	0	0
CHEK1	0.011	0	-9999	-10000	0	0
mol:HEME	0.011	0.003	-9999	-10000	0	0
PER1	0.009	0.026	-9999	-0.41	2	2
BMAL/CLOCK/NPAS2	0.033	0.027	-9999	-0.22	6	6
BMAL1/CLOCK	0.04	0.019	-9999	-10000	0	0
S phase of mitotic cell cycle	0.039	0.011	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	0.039	0.011	-9999	-10000	0	0
mol:NADPH	0.011	0.003	-9999	-10000	0	0
PER1/TIMELESS	0.034	0.017	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	0.001	0.004	-9999	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
HDAC1	0.011	-9999	-9999
Ran/GTP/Exportin 1/HDAC4	0	-9999	-9999
MDM2/SUMO1	0.025	-9999	-9999
HDAC4	0.011	-9999	-9999
Ran/GTP/Exportin 1/HDAC1	0	-9999	-9999
SUMO1	0.011	-9999	-9999
NPC/RanGAP1/SUMO1	0.014	-9999	-9999
mol:GTP	0	-9999	-9999
XPO1	0.023	-9999	-9999
EntrezGene:23636	0	-9999	-9999
RAN	0.011	-9999	-9999
EntrezGene:8021	0	-9999	-9999
RANBP2	0.011	-9999	-9999
SUMO1/HDAC4	0.025	-9999	-9999
SUMO1/HDAC1	0.025	-9999	-9999
RANGAP1	0.011	-9999	-9999
MDM2/SUMO1/SUMO1	0.028	-9999	-9999
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.017	-9999	-9999
Ran/GTP	0.022	-9999	-9999
EntrezGene:23225	0	-9999	-9999
MDM2	0.011	-9999	-9999
UBE2I	0.011	-9999	-9999
Ran/GTP/Exportin 1	0.027	-9999	-9999
NPC	0.007	-9999	-9999
PIAS2	0.011	-9999	-9999
PIAS1	0.011	-9999	-9999
EntrezGene:9972	0	-9999	-9999

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0	0	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.016	0.004	-9999	-10000	0	0
AP2	0.016	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0.016	0	-9999	-10000	0	0
CLTB	0.011	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.021	0	-9999	-10000	0	0
CD4	0.01	0.015	-9999	-0.33	1	1
CLTA	0.011	0	-9999	-10000	0	0
mol:GTP	0.001	0	-9999	-10000	0	0
ARFGAP1	0.009	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0.006	-9999	-0.15	1	1
ARF1/GTP	0	0.003	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.022	0	-9999	-10000	0	0
mol:Choline	0	0.007	-9999	-0.15	1	1
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.011	0	-9999	-10000	0	0
DDEF1	0	0.007	-9999	-0.16	1	1
ARF1/GDP	0	0.002	-9999	-10000	0	0
AP2M1	0.011	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0.014	0	-9999	-10000	0	0
Rac/GTP	0.009	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.021	0	-9999	-10000	0	0
ARFIP2	0.01	0	-9999	-10000	0	0
COPA	0.011	0	-9999	-10000	0	0
RAC1	0.011	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.021	0.002	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0.008	0	-9999	-10000	0	0
GGA3	0.011	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0.015	0.003	-9999	-10000	0	0
AP2A1	0.011	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.022	0	-9999	-10000	0	0
ARF1/GDP/Membrin	0.015	0.003	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0.014	0	-9999	-10000	0	0
CYTH2	0.011	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0.016	0	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0.008	0	-9999	-10000	0	0
mol:Brefeldin A	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.028	0.003	-9999	-10000	0	0
PLD2	0	0.007	-9999	-0.15	1	1
ARF-GAP1/v-SNARE	0.009	0	-9999	-10000	0	0
PIP5K1A	0	0.006	-9999	-0.15	1	1
ARF1/GTP/Membrin/GBF1/p115	0	0.003	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0.007	-9999	-0.15	1	1
KDEL Receptor/Ligand/ARF-GAP1	0.009	0	-9999	-10000	0	0
GOSR2	0	0	-9999	-10000	0	0
USO1	0	0	-9999	-10000	0	0
GBF1	0	0	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0.016	0.001	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.022	0.008	-9999	-0.17	1	1

×

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	0.016	0	-9999	-10000	0	0
FBXW11	0.011	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.011	0	-9999	-10000	0	0
CHUK	0.011	0	-9999	-10000	0	0
NF kappa B2 p100/RelB	0.033	0	-9999	-10000	0	0
NFKB1	0.01	0.018	-9999	-0.41	1	1
MAP3K14	0.011	0	-9999	-10000	0	0
NF kappa B1 p50/RelB	0.016	0.013	-9999	-0.28	1	1
RELB	0.011	0	-9999	-10000	0	0
NFKB2	0.011	0	-9999	-10000	0	0
NF kappa B2 p52/RelB	0.015	0	-9999	-10000	0	0
regulation of B cell activation	0.015	0	-9999	-10000	0	0

pid_entity	TCGA.SL.A6JA	TCGA.SL.A6J9	TCGA.SJ.A6ZJ	TCGA.SJ.A6ZI
109_MAP3K5	-0.13	0.043	0.043	0.043
47_PPARGC1A	-0.41	0.011	0.011	-0.41
105_BMP4	0.011	-0.41	0.011	0.011
105_BMP6	0.011	0.011	0.011	0.011
105_BMP7	0.011	0.011	0.011	0.011
105_BMP2	0.011	-0.41	0.011	0.011
131_RELN/VLDLR	-0.2	-0.2	0.028	-0.2
30_TGFB1/TGF beta receptor Type II	0.011	0.011	0.013	0.01
84_STAT5B	-0.023	-0.091	-0.024	0.038
84_STAT5A	-0.023	-0.091	-0.024	0.038