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

Pathway.Name	Avg.Num.Perturbations
FOXM1 transcription factor network	227
Glypican 2 network	178
Angiopoietin receptor Tie2-mediated signaling	153
HIF-1-alpha transcription factor network	134
Aurora B signaling	124
Signaling events mediated by the Hedgehog family	98
Endothelins	79
PLK1 signaling events	75
Aurora C signaling	70
Visual signal transduction: Cones	64

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	0.4408	227	11623	51	-0.033	0.78	1000	-1000	-0.096	-1000
Glypican 2 network	0.3456	178	713	4	0.093	0.14	1000	-1000	0.016	-1000
Angiopoietin receptor Tie2-mediated signaling	0.2971	153	13501	88	-0.59	0.11	1000	-1000	-0.056	-1000
HIF-1-alpha transcription factor network	0.2602	134	10212	76	-0.061	0.43	1000	-1000	-0.035	-1000
Aurora B signaling	0.2408	124	8334	67	-0.13	0.28	1000	-1000	-0.028	-1000
Signaling events mediated by the Hedgehog family	0.1903	98	5132	52	-0.22	0.1	1000	-1000	-0.028	-1000
Endothelins	0.1534	79	7628	96	-0.31	0.2	1000	-1000	-0.034	-1000
PLK1 signaling events	0.1456	75	6437	85	-0.049	0.2	1000	-1000	-0.024	-1000
Aurora C signaling	0.1359	70	495	7	0	0.16	1000	-1000	-0.006	-1000
Visual signal transduction: Cones	0.1243	64	2461	38	-0.081	0.12	1000	-1000	-0.017	-1000
Signaling mediated by p38-alpha and p38-beta	0.1204	62	2764	44	-0.1	0.021	1000	-1000	-0.022	-1000
FOXA2 and FOXA3 transcription factor networks	0.1107	57	2649	46	-0.2	0.16	1000	-1000	-0.088	-1000
Signaling events regulated by Ret tyrosine kinase	0.1107	57	4732	82	-0.076	0.059	1000	-1000	-0.046	-1000
Fc-epsilon receptor I signaling in mast cells	0.1087	56	5450	97	-0.095	0.021	1000	-1000	-0.045	-1000
BMP receptor signaling	0.1029	53	4338	81	-0.19	0.22	1000	-1000	-0.019	-1000
Osteopontin-mediated events	0.1010	52	1997	38	0	0.23	1000	-1000	-0.018	-1000
amb2 Integrin signaling	0.1010	52	4285	82	-0.29	0.084	1000	-1000	-0.025	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.1010	52	2747	52	-0.14	0.045	1000	-1000	-0.028	-1000
IL4-mediated signaling events	0.0990	51	4693	91	-0.62	0.34	1000	-1000	-0.11	-1000
Ephrin B reverse signaling	0.0913	47	2267	48	-0.079	0.077	1000	-1000	-0.024	-1000
Visual signal transduction: Rods	0.0893	46	2407	52	-0.081	0.1	1000	-1000	-0.025	-1000
Syndecan-1-mediated signaling events	0.0854	44	1509	34	0	0.21	1000	-1000	-0.02	-1000
p75(NTR)-mediated signaling	0.0777	40	5002	125	-0.15	0.13	1000	-1000	-0.044	-1000
Thromboxane A2 receptor signaling	0.0738	38	4053	105	-0.12	0.071	1000	-1000	-0.037	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0718	37	2538	68	-0.16	0.071	1000	-1000	-0.062	-1000
Arf6 signaling events	0.0699	36	2269	62	-0.11	0.071	1000	-1000	-0.026	-1000
TCGA08_retinoblastoma	0.0699	36	290	8	-0.023	0.098	1000	-1000	-0.003	-1000
IL23-mediated signaling events	0.0699	36	2181	60	-0.21	0.025	1000	-1000	-0.09	-1000
LPA4-mediated signaling events	0.0680	35	420	12	-0.071	0	1000	-1000	-0.016	-1000
Integrins in angiogenesis	0.0680	35	2968	84	-0.069	0.23	1000	-1000	-0.038	-1000
Canonical Wnt signaling pathway	0.0680	35	1803	51	-0.21	0.095	1000	-1000	-0.033	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0660	34	4175	120	-0.16	0.14	1000	-1000	-0.035	-1000
Presenilin action in Notch and Wnt signaling	0.0621	32	1995	61	-0.21	0.095	1000	-1000	-0.038	-1000
EGFR-dependent Endothelin signaling events	0.0621	32	681	21	-0.027	0.071	1000	-1000	-0.029	-1000
Glypican 1 network	0.0602	31	1498	48	-0.066	0.037	1000	-1000	-0.02	-1000
Reelin signaling pathway	0.0602	31	1786	56	-0.037	0.049	1000	-1000	-0.022	-1000
TCGA08_p53	0.0602	31	218	7	-0.022	0.019	1000	-1000	-0.009	-1000
IL6-mediated signaling events	0.0602	31	2398	75	-0.15	0.056	1000	-1000	-0.041	-1000
Glucocorticoid receptor regulatory network	0.0583	30	3437	114	-0.25	0.16	1000	-1000	-0.046	-1000
Aurora A signaling	0.0563	29	1767	60	-0.029	0.18	1000	-1000	-0.018	-1000
Effects of Botulinum toxin	0.0563	29	768	26	0	0.045	1000	-1000	-0.01	-1000
Wnt signaling	0.0544	28	196	7	-0.021	0.04	1000	-1000	-0.01	-1000
HIF-2-alpha transcription factor network	0.0524	27	1201	43	-0.13	0.14	1000	-1000	-0.032	-1000
Nongenotropic Androgen signaling	0.0485	25	1316	52	-0.056	0.041	1000	-1000	-0.021	-1000
Noncanonical Wnt signaling pathway	0.0466	24	641	26	-0.042	0.04	1000	-1000	-0.026	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0466	24	795	33	-0.07	0.096	1000	-1000	-0.028	-1000
ErbB4 signaling events	0.0447	23	1636	69	-0.11	0.15	1000	-1000	-0.022	-1000
IL1-mediated signaling events	0.0447	23	1445	62	-0.081	0.042	1000	-1000	-0.035	-1000
Syndecan-4-mediated signaling events	0.0447	23	1585	67	-0.042	0.12	1000	-1000	-0.031	-1000
PDGFR-alpha signaling pathway	0.0427	22	981	44	-0.19	0.04	1000	-1000	-0.025	-1000
Regulation of Androgen receptor activity	0.0427	22	1562	70	-0.14	0.12	1000	-1000	-0.033	-1000
Syndecan-2-mediated signaling events	0.0408	21	1509	69	-0.049	0.053	1000	-1000	-0.03	-1000
Nectin adhesion pathway	0.0408	21	1369	63	-0.047	0.052	1000	-1000	-0.037	-1000
FoxO family signaling	0.0408	21	1402	64	-0.001	0.2	1000	-1000	-0.044	-1000
LPA receptor mediated events	0.0408	21	2185	102	-0.056	0.085	1000	-1000	-0.052	-1000
ErbB2/ErbB3 signaling events	0.0388	20	1304	65	-0.051	0.03	1000	-1000	-0.048	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0388	20	694	34	-0.035	0.06	1000	-1000	-0.025	-1000
Ceramide signaling pathway	0.0369	19	1477	76	-0.019	0.071	1000	-1000	-0.025	-1000
Class IB PI3K non-lipid kinase events	0.0369	19	57	3	-0.008	0.008	1000	-1000	-0.019	-1000
Coregulation of Androgen receptor activity	0.0350	18	1383	76	-0.059	0.096	1000	-1000	-0.023	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0350	18	1017	54	-0.034	0.1	1000	-1000	-0.029	-1000
Signaling events mediated by PTP1B	0.0350	18	1377	76	-0.057	0.072	1000	-1000	-0.03	-1000
FAS signaling pathway (CD95)	0.0350	18	874	47	-0.24	0.034	1000	-1000	-0.021	-1000
EPHB forward signaling	0.0350	18	1562	85	-0.032	0.085	1000	-1000	-0.044	-1000
PLK2 and PLK4 events	0.0330	17	52	3	-0.007	0.036	1000	-1000	-0.018	-1000
TCR signaling in naïve CD8+ T cells	0.0330	17	1651	93	-0.04	0.033	1000	-1000	-0.032	-1000
Calcium signaling in the CD4+ TCR pathway	0.0330	17	539	31	-0.039	0.028	1000	-1000	-0.043	-1000
BCR signaling pathway	0.0330	17	1736	99	-0.051	0.084	1000	-1000	-0.038	-1000
Plasma membrane estrogen receptor signaling	0.0330	17	1491	86	-0.061	0.058	1000	-1000	-0.037	-1000
Caspase cascade in apoptosis	0.0311	16	1250	74	-0.03	0.088	1000	-1000	-0.027	-1000
IL12-mediated signaling events	0.0311	16	1478	87	-0.13	0.057	1000	-1000	-0.07	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0291	15	1353	85	-0.045	0.035	1000	-1000	-0.035	-1000
S1P1 pathway	0.0291	15	550	36	-0.087	0.02	1000	-1000	-0.025	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0291	15	1920	125	-0.19	0.042	1000	-1000	-0.041	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0291	15	1238	78	-0.043	0.023	1000	-1000	-0.045	-1000
Syndecan-3-mediated signaling events	0.0272	14	494	35	-0.12	0.046	1000	-1000	-0.021	-1000
Regulation of p38-alpha and p38-beta	0.0272	14	809	54	-0.036	0.064	1000	-1000	-0.038	-1000
BARD1 signaling events	0.0252	13	769	57	-0.046	0.12	1000	-1000	-0.039	-1000
Signaling events mediated by HDAC Class III	0.0252	13	553	40	-0.062	0.059	1000	-1000	-0.029	-1000
IL27-mediated signaling events	0.0252	13	664	51	-0.046	0.029	1000	-1000	-0.039	-1000
S1P4 pathway	0.0252	13	347	25	-0.019	0.027	1000	-1000	-0.012	-1000
S1P5 pathway	0.0214	11	199	17	-0.016	0.021	1000	-1000	-0.004	-1000
Signaling events mediated by PRL	0.0214	11	400	34	-0.02	0.086	1000	-1000	-0.033	-1000
IL2 signaling events mediated by STAT5	0.0194	10	227	22	-0.024	0.089	1000	-1000	-0.028	-1000
Class I PI3K signaling events	0.0194	10	753	73	-0.034	0.064	1000	-1000	-0.026	-1000
PDGFR-beta signaling pathway	0.0194	10	1051	97	-0.032	0.052	1000	-1000	-0.038	-1000
Regulation of nuclear SMAD2/3 signaling	0.0175	9	1261	136	-0.17	0.071	1000	-1000	-0.023	-1000
Ephrin A reverse signaling	0.0175	9	64	7	-0.012	0.028	1000	-1000	-0.007	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0175	9	407	45	-0.017	0.05	1000	-1000	-0.03	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0175	9	676	74	-0.088	0.071	1000	-1000	-0.044	-1000
Insulin Pathway	0.0175	9	668	74	-0.098	0.051	1000	-1000	-0.036	-1000
VEGFR1 specific signals	0.0175	9	504	56	-0.19	0.049	1000	-1000	-0.028	-1000
Cellular roles of Anthrax toxin	0.0155	8	312	39	-0.032	0.028	1000	-1000	-0.015	-1000
Hedgehog signaling events mediated by Gli proteins	0.0155	8	567	65	-0.14	0.048	1000	-1000	-0.028	-1000
mTOR signaling pathway	0.0155	8	435	53	-0.058	0.025	1000	-1000	-0.033	-1000
IFN-gamma pathway	0.0155	8	608	68	-0.029	0.064	1000	-1000	-0.038	-1000
ceramide signaling pathway	0.0155	8	419	49	-0.007	0.029	1000	-1000	-0.021	-1000
Regulation of Telomerase	0.0155	8	822	102	-0.02	0.1	1000	-1000	-0.032	-1000
JNK signaling in the CD4+ TCR pathway	0.0136	7	132	17	-0.012	0.047	1000	-1000	-0.03	-1000
EPO signaling pathway	0.0136	7	429	55	-0.025	0.045	1000	-1000	-0.028	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0136	7	622	83	-0.058	0.049	1000	-1000	-0.023	-1000
Retinoic acid receptors-mediated signaling	0.0136	7	460	58	-0.092	0.049	1000	-1000	-0.028	-1000
Arf6 trafficking events	0.0136	7	519	71	-0.038	0.038	1000	-1000	-0.031	-1000
p38 MAPK signaling pathway	0.0136	7	314	44	-0.006	0.064	1000	-1000	-0.015	-1000
Ras signaling in the CD4+ TCR pathway	0.0136	7	130	17	-0.003	0.032	1000	-1000	-0.015	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0117	6	184	28	-0.014	0.034	1000	-1000	-0.014	-1000
Signaling events mediated by HDAC Class I	0.0117	6	650	104	-0.035	0.048	1000	-1000	-0.029	-1000
IL2 signaling events mediated by PI3K	0.0117	6	372	58	-0.014	0.08	1000	-1000	-0.03	-1000
TCGA08_rtk_signaling	0.0117	6	158	26	-0.011	0.047	1000	-1000	-0.008	-1000
IGF1 pathway	0.0117	6	375	57	-0.032	0.048	1000	-1000	-0.029	-1000
Signaling events mediated by HDAC Class II	0.0097	5	387	75	-0.021	0.056	1000	-1000	-0.023	-1000
Signaling mediated by p38-gamma and p38-delta	0.0097	5	77	15	-0.018	0.022	1000	-1000	-0.019	-1000
E-cadherin signaling in the nascent adherens junction	0.0097	5	415	76	-0.031	0.051	1000	-1000	-0.043	-1000
E-cadherin signaling in keratinocytes	0.0097	5	234	43	-0.014	0.039	1000	-1000	-0.025	-1000
Circadian rhythm pathway	0.0078	4	90	22	-0.004	0.046	1000	-1000	-0.026	-1000
Arf6 downstream pathway	0.0078	4	181	43	-0.046	0.047	1000	-1000	-0.021	-1000
Class I PI3K signaling events mediated by Akt	0.0078	4	316	68	-0.028	0.044	1000	-1000	-0.016	-1000
S1P3 pathway	0.0078	4	179	42	-0.022	0.034	1000	-1000	-0.022	-1000
TRAIL signaling pathway	0.0058	3	165	48	-0.017	0.046	1000	-1000	-0.019	-1000
Canonical NF-kappaB pathway	0.0039	2	107	39	-0.015	0.042	1000	-1000	-0.019	-1000
Insulin-mediated glucose transport	0.0039	2	76	32	-0.016	0.038	1000	-1000	-0.022	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0039	2	103	37	-0.024	0.05	1000	-1000	-0.02	-1000
Rapid glucocorticoid signaling	0.0039	2	50	20	-0.008	0.026	1000	-1000	-0.009	-1000
Arf1 pathway	0.0039	2	152	54	-0.008	0.034	1000	-1000	-0.012	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0019	1	28	23	0	0.036	1000	-1000	-0.015	-1000
a4b1 and a4b7 Integrin signaling	0.0019	1	7	5	0.02	0.03	1000	-1000	0.017	-1000
Paxillin-dependent events mediated by a4b1	0.0019	1	66	36	-0.037	0.039	1000	-1000	-0.022	-1000
Atypical NF-kappaB pathway	0.0019	1	45	31	-0.017	0.029	1000	-1000	-0.018	-1000
E-cadherin signaling events	0.0019	1	6	5	0.019	0.039	1000	-1000	0.015	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	23	27	-0.019	0.045	1000	-1000	-0.027	-1000
Alternative NF-kappaB pathway	0.0000	0	0	13	0	0.056	1000	-1000	0	-1000
Total	NA	3506	207508	7203	-9.6	11	131000	-131000	-3.8	-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	0.63	0.47	1	272	-10000	0	272
PLK1	0.36	0.32	0.67	240	-0.68	2	242
BIRC5	0.4	0.32	0.7	241	-0.72	2	243
HSPA1B	0.64	0.48	1	271	-10000	0	271
MAP2K1	0.19	0.15	0.32	254	-10000	0	254
BRCA2	0.63	0.48	1	272	-10000	0	272
FOXM1	0.78	0.62	1.3	281	-10000	0	281
XRCC1	0.63	0.48	1	267	-10000	0	267
FOXM1B/p19	0.21	0.35	0.84	103	-0.84	1	104
Cyclin D1/CDK4	0.52	0.43	0.92	253	-10000	0	253
CDC2	0.7	0.55	1.1	287	-10000	0	287
TGFA	0.57	0.45	0.95	272	-10000	0	272
SKP2	0.69	0.53	1.1	283	-10000	0	283
CCNE1	0.16	0.16	0.38	175	-10000	0	175
CKS1B	0.63	0.48	1	288	-10000	0	288
RB1	0.37	0.36	0.72	235	-0.61	3	238
FOXM1C/SP1	0.56	0.42	0.92	256	-10000	0	256
AURKB	0.34	0.36	0.69	225	-0.71	16	241
CENPF	0.72	0.55	1.2	288	-10000	0	288
CDK4	0.086	0.068	0.2	67	-10000	0	67
MYC	0.42	0.42	0.86	221	-10000	0	221
CHEK2	0.19	0.15	0.33	250	-10000	0	250
ONECUT1	0.61	0.48	1	270	-10000	0	270
CDKN2A	-0.033	0.15	0.26	50	-0.22	138	188
LAMA4	0.62	0.49	1	278	-1.1	4	282
FOXM1B/HNF6	0.62	0.49	1	264	-10000	0	264
FOS	0.58	0.51	1	257	-0.94	2	259
SP1	0.022	0.005	-10000	0	-10000	0	0
CDC25B	0.63	0.48	1	271	-10000	0	271
response to radiation	0.13	0.11	0.23	258	-10000	0	258
CENPB	0.63	0.48	1	271	-10000	0	271
CENPA	0.72	0.56	1.2	286	-10000	0	286
NEK2	0.74	0.56	1.2	296	-10000	0	296
HIST1H2BA	0.63	0.48	1	272	-10000	0	272
CCNA2	0.13	0.15	0.39	116	-10000	0	116
EP300	0.02	0.005	-10000	0	-10000	0	0
CCNB1/CDK1	0.68	0.53	1.1	265	-10000	0	265
CCNB2	0.7	0.55	1.2	279	-10000	0	279
CCNB1	0.72	0.57	1.2	279	-10000	0	279
ETV5	0.62	0.5	1	265	-1.1	2	267
ESR1	0.61	0.5	1	270	-1.1	4	274
CCND1	0.6	0.47	1	274	-10000	0	274
GSK3A	0.15	0.11	0.26	228	-10000	0	228
Cyclin A-E1/CDK1-2	0.26	0.21	0.43	275	-10000	0	275
CDK2	0.06	0.039	0.18	1	-10000	0	1
G2/M transition of mitotic cell cycle	0.17	0.14	0.29	278	-10000	0	278
FOXM1B/Cbp/p300	0.16	0.26	0.71	51	-10000	0	51
GAS1	0.6	0.51	1	269	-1	6	275
MMP2	0.63	0.48	1	274	-10000	0	274
RB1/FOXM1C	0.5	0.43	0.92	245	-10000	0	245
CREBBP	0.021	0.004	-10000	0	-10000	0	0

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	0.11	0.14	0.32	151	-9999	151
GPC2	0.093	0.13	0.32	124	-9999	124
GPC2/Midkine	0.14	0.14	0.28	219	-9999	219
neuron projection morphogenesis	0.14	0.14	0.28	219	-9999	219

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.46	0.48	-10000	0	-0.94	246	246
NCK1/PAK1/Dok-R	-0.22	0.21	-10000	0	-0.43	247	247
NCK1/Dok-R	-0.51	0.58	-10000	0	-1.1	243	243
PIK3CA	0.022	0.005	-10000	0	-10000	0	0
mol:beta2-estradiol	0.063	0.096	0.23	127	-10000	0	127
RELA	0.021	0.004	-10000	0	-10000	0	0
SHC1	0.017	0.015	0.32	1	-10000	0	1
Rac/GDP	0.014	0.005	-10000	0	-10000	0	0
F2	0.11	0.16	0.32	174	-10000	0	174
TNIP2	0.021	0.004	-10000	0	-10000	0	0
NF kappa B/RelA	-0.46	0.54	-10000	0	-0.99	244	244
FN1	0.019	0.033	0.32	1	-0.33	4	5
PLD2	-0.53	0.6	-10000	0	-1.1	244	244
PTPN11	0.021	0.004	-10000	0	-10000	0	0
GRB14	0.034	0.078	0.32	28	-0.33	5	33
ELK1	-0.48	0.52	-10000	0	-0.99	245	245
GRB7	0.019	0.022	-10000	0	-0.33	2	2
PAK1	0.02	0.005	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.48	0.57	-10000	0	-1	243	243
CDKN1A	-0.33	0.32	-10000	0	-0.65	243	243
ITGA5	0.021	0.021	0.32	1	-0.33	1	2
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.51	0.58	-10000	0	-1.1	244	244
CRK	0.019	0.006	-10000	0	-10000	0	0
mol:NO	-0.33	0.34	-10000	0	-0.68	244	244
PLG	-0.53	0.6	-10000	0	-1.1	244	244
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.43	0.44	-10000	0	-0.88	245	245
GRB2	0.02	0.004	-10000	0	-10000	0	0
PIK3R1	0.012	0.021	-10000	0	-0.33	1	1
ANGPT2	-0.3	0.32	-10000	0	-0.71	163	163
BMX	-0.58	0.62	-10000	0	-1.2	244	244
ANGPT1	-0.32	0.49	-10000	0	-1.2	128	128
tube development	-0.37	0.36	-10000	0	-0.73	246	246
ANGPT4	-0.16	0.17	-10000	0	-0.33	249	249
response to hypoxia	-0.032	0.032	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.54	0.63	-10000	0	-1.1	243	243
alpha5/beta1 Integrin	0.03	0.016	0.23	1	-0.23	1	2
FGF2	-0.026	0.12	-10000	0	-0.32	70	70
STAT5A (dimer)	-0.43	0.42	-10000	0	-0.85	244	244
mol:L-citrulline	-0.33	0.34	-10000	0	-0.68	244	244
AGTR1	-0.088	0.16	0.32	1	-0.33	161	162
MAPK14	-0.59	0.64	-10000	0	-1.2	247	247
Tie2/SHP2	-0.46	0.53	-10000	0	-1	222	222
TEK	-0.51	0.58	-10000	0	-1.1	222	222
RPS6KB1	-0.44	0.46	-10000	0	-0.9	246	246
Angiotensin II/AT1	-0.058	0.11	0.22	1	-0.22	161	162
Tie2/Ang1/GRB2	-0.54	0.63	-10000	0	-1.1	244	244
MAPK3	-0.49	0.53	-10000	0	-1	244	244
MAPK1	-0.48	0.53	-10000	0	-1	241	241
Tie2/Ang1/GRB7	-0.54	0.63	-10000	0	-1.1	244	244
NFKB1	0.021	0.003	-10000	0	-10000	0	0
MAPK8	-0.53	0.6	-10000	0	-1.1	244	244
PI3K	-0.54	0.57	-10000	0	-1.1	246	246
FES	-0.59	0.63	-10000	0	-1.2	247	247
Crk/Dok-R	-0.51	0.58	-10000	0	-1.1	244	244
Tie2/Ang1/ABIN2	-0.54	0.63	-10000	0	-1.1	244	244
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.41	0.42	-10000	0	-0.83	246	246
STAT5A	0.02	0.016	-10000	0	-0.33	1	1
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.43	0.46	-10000	0	-0.88	246	246
Tie2/Ang2	-0.53	0.53	-10000	0	-1	245	245
Tie2/Ang1	-0.58	0.67	-10000	0	-1.2	244	244
FOXO1	-0.41	0.42	-10000	0	-0.84	246	246
ELF1	-0.034	0.067	-10000	0	-10000	0	0
ELF2	-0.53	0.6	-10000	0	-1.1	243	243
mol:Choline	-0.5	0.56	-10000	0	-1	244	244
cell migration	-0.12	0.11	-10000	0	-0.24	247	247
FYN	-0.43	0.42	-10000	0	-0.85	246	246
DOK2	-0.004	0.085	-10000	0	-0.33	33	33
negative regulation of cell cycle	-0.3	0.28	-10000	0	-0.59	244	244
ETS1	-0.055	0.11	-10000	0	-0.25	117	117
PXN	-0.35	0.37	-10000	0	-0.72	246	246
ITGB1	0.021	0.004	-10000	0	-10000	0	0
NOS3	-0.38	0.39	-10000	0	-0.78	244	244
RAC1	0.019	0.007	-10000	0	-10000	0	0
TNF	-0.064	0.12	-10000	0	-0.26	130	130
MAPKKK cascade	-0.5	0.56	-10000	0	-1	244	244
RASA1	0.02	0.005	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.54	0.62	-10000	0	-1.1	244	244
NCK1	0.021	0.003	-10000	0	-10000	0	0
vasculogenesis	-0.3	0.3	-10000	0	-0.6	244	244
mol:Phosphatidic acid	-0.5	0.56	-10000	0	-1	244	244
mol:Angiotensin II	0	0.002	-10000	0	-10000	0	0
mol:NADP	-0.33	0.34	-10000	0	-0.68	244	244
Rac1/GTP	-0.4	0.42	-10000	0	-0.82	246	246
MMP2	-0.53	0.6	-10000	0	-1.1	244	244

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	0.25	0.24	0.49	194	-0.65	5	199
HDAC7	0.031	0.015	-10000	0	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	0.31	0.31	0.64	183	-0.88	3	186
SMAD4	0.018	0.01	-10000	0	-10000	0	0
ID2	0.28	0.24	0.51	189	-0.64	6	195
AP1	0.002	0.071	-10000	0	-0.24	31	31
ABCG2	0.26	0.25	0.52	160	-0.63	7	167
HIF1A	0.1	0.091	0.23	102	-0.22	2	104
TFF3	0.31	0.28	0.57	204	-0.74	4	208
GATA2	-0.017	0.098	-10000	0	-0.33	42	42
AKT1	0.097	0.099	0.24	96	-0.25	4	100
response to hypoxia	0.078	0.095	0.2	139	-0.23	8	147
MCL1	0.23	0.23	0.53	125	-0.68	3	128
NDRG1	0.24	0.24	0.53	135	-0.67	4	139
SERPINE1	0.27	0.24	0.54	152	-0.71	4	156
FECH	0.26	0.24	0.52	166	-0.71	4	170
FURIN	0.28	0.24	0.55	161	-0.71	4	165
NCOA2	0.016	0.035	-10000	0	-0.33	5	5
EP300	0.12	0.14	0.28	133	-0.3	13	146
HMOX1	0.28	0.24	0.51	185	-0.67	4	189
BHLHE40	0.28	0.24	0.54	158	-0.71	4	162
BHLHE41	0.26	0.24	0.51	171	-0.68	6	177
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.14	0.14	0.34	108	-0.32	1	109
ENG	0.11	0.098	0.26	63	-0.32	3	66
JUN	0.009	0.037	-10000	0	-0.34	3	3
RORA	0.27	0.24	0.51	182	-0.74	4	186
ABCB1	0.006	0.18	0.37	24	-0.73	21	45
TFRC	0.26	0.24	0.53	150	-0.71	4	154
CXCR4	0.28	0.23	0.53	157	-0.71	4	161
TF	0.32	0.29	0.6	205	-0.66	5	210
CITED2	0.27	0.24	0.53	156	-0.71	4	160
HIF1A/ARNT	0.43	0.4	0.84	197	-0.77	4	201
LDHA	0.053	0.11	0.42	11	-0.54	2	13
ETS1	0.27	0.24	0.53	155	-0.63	4	159
PGK1	0.28	0.23	0.52	169	-0.71	4	173
NOS2	0.27	0.26	0.54	160	-0.77	4	164
ITGB2	0.28	0.24	0.53	158	-0.84	4	162
ALDOA	0.28	0.24	0.54	157	-0.71	4	161
Cbp/p300/CITED2	0.28	0.28	0.57	170	-0.91	4	174
FOS	-0.007	0.082	-10000	0	-0.34	27	27
HK2	0.28	0.24	0.51	186	-0.72	5	191
SP1	0.015	0.036	-10000	0	-0.17	13	13
GCK	0.16	0.25	0.51	52	-1	12	64
HK1	0.28	0.24	0.52	169	-0.71	4	173
NPM1	0.27	0.24	0.51	179	-0.71	4	183
EGLN1	0.26	0.24	0.52	169	-0.73	3	172
CREB1	0.023	0.009	0.16	1	-10000	0	1
PGM1	0.28	0.24	0.51	182	-0.71	4	186
SMAD3	0.02	0.008	-10000	0	-10000	0	0
EDN1	-0.061	0.41	0.41	4	-0.99	78	82
IGFBP1	0.29	0.26	0.59	159	-0.71	4	163
VEGFA	0.26	0.23	0.5	171	-0.72	3	174
HIF1A/JAB1	0.08	0.067	0.21	43	-0.18	1	44
CP	0.38	0.29	0.6	266	-0.7	4	270
CXCL12	0.27	0.25	0.54	153	-0.76	5	158
COPS5	0.02	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4	0.027	0.014	-10000	0	-10000	0	0
BNIP3	0.27	0.24	0.52	172	-0.71	4	176
EGLN3	0.31	0.29	0.62	179	-0.63	4	183
CA9	0.4	0.3	0.61	288	-0.7	4	292
TERT	0.29	0.29	0.61	185	-0.64	4	189
ENO1	0.28	0.24	0.53	158	-0.71	4	162
PFKL	0.28	0.23	0.52	170	-0.71	4	174
NCOA1	0.021	0.003	-10000	0	-10000	0	0
ADM	0.28	0.24	0.52	185	-0.74	4	189
ARNT	0.09	0.086	0.23	86	-10000	0	86
HNF4A	0.069	0.13	0.32	96	-0.29	13	109
ADFP	0.25	0.24	0.49	194	-0.65	5	199
SLC2A1	0.33	0.28	0.58	216	-0.62	4	220
LEP	0.29	0.26	0.55	188	-0.71	4	192
HIF1A/ARNT/Cbp/p300	0.32	0.32	0.67	183	-0.9	3	186
EPO	0.23	0.23	0.51	130	-0.69	3	133
CREBBP	0.12	0.13	0.28	127	-0.27	12	139
HIF1A/ARNT/Cbp/p300/HDAC7	0.35	0.33	0.69	192	-0.84	3	195
PFKFB3	0.27	0.24	0.51	181	-0.7	4	185
NT5E	0.28	0.25	0.53	181	-0.71	4	185

Aurora B signaling

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
Condensin I complex	0.11	0.12	0.24	196	-0.19	5	201
STMN1	0.069	0.087	0.16	245	-10000	0	245
Aurora B/RasGAP/Survivin	0.21	0.17	0.36	281	-10000	0	281
Chromosomal passenger complex/Cul3 protein complex	0.089	0.11	0.2	196	-0.26	4	200
BIRC5	0.19	0.16	0.33	276	-10000	0	276
DES	-0.13	0.28	-10000	0	-0.56	98	98
Aurora C/Aurora B/INCENP	0.12	0.096	0.22	239	-0.16	3	242
Aurora B/TACC1	0.089	0.1	0.21	202	-0.15	17	219
Aurora B/PP2A	0.12	0.1	0.23	232	-10000	0	232
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	0.035	0.036	0.14	18	-10000	0	18
mitotic metaphase/anaphase transition	-0.004	0.006	-10000	0	-10000	0	0
NDC80	0.14	0.15	0.27	273	-10000	0	273
Cul3 protein complex	0.028	0.049	0.22	3	-0.19	20	23
KIF2C	0.16	0.12	0.26	301	-10000	0	301
PEBP1	0.023	0.005	-10000	0	-10000	0	0
KIF20A	0.18	0.15	0.32	265	-10000	0	265
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.12	0.1	0.23	239	-10000	0	239
SEPT1	0.02	0.016	-10000	0	-0.33	1	1
SMC2	0.021	0.004	-10000	0	-10000	0	0
SMC4	0.02	0.004	-10000	0	-10000	0	0
NSUN2/NPM1/Nucleolin	0.1	0.18	0.3	122	-0.44	30	152
PSMA3	0.021	0.004	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.005	0.006	-10000	0	-10000	0	0
H3F3B	0.074	0.071	0.15	248	-10000	0	248
AURKB	0.17	0.16	0.33	247	-10000	0	247
AURKC	0.02	0.035	0.32	3	-0.33	3	6
CDCA8	0.13	0.15	0.34	167	-10000	0	167
cytokinesis	0.14	0.15	0.3	218	-0.36	2	220
Aurora B/Septin1	0.18	0.18	0.36	224	-0.27	5	229
AURKA	0.053	0.12	0.32	86	-10000	0	86
INCENP	0.027	0.01	-10000	0	-10000	0	0
KLHL13	0.009	0.071	0.32	3	-0.33	20	23
BUB1	0.085	0.14	0.32	128	-10000	0	128
hSgo1/Aurora B/Survivin	0.28	0.24	0.46	290	-10000	0	290
EVI5	0.026	0.007	-10000	0	-10000	0	0
RhoA/GTP	0.16	0.15	0.33	188	-0.32	1	189
SGOL1	0.15	0.15	0.32	226	-10000	0	226
CENPA	0.16	0.16	0.3	263	-0.25	5	268
NCAPG	0.14	0.15	0.32	205	-10000	0	205
Aurora B/HC8 Proteasome	0.12	0.1	0.23	239	-10000	0	239
NCAPD2	0.02	0.005	-10000	0	-10000	0	0
Aurora B/PP1-gamma	0.12	0.1	0.23	242	-10000	0	242
RHOA	0.02	0.004	-10000	0	-10000	0	0
NCAPH	0.15	0.15	0.32	217	-10000	0	217
NPM1	0.072	0.13	0.2	80	-0.35	22	102
RASA1	0.02	0.005	-10000	0	-10000	0	0
KLHL9	0.018	0.008	-10000	0	-10000	0	0
mitotic prometaphase	0.002	0.003	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.12	0.1	0.23	239	-10000	0	239
PPP1CC	0.021	0.003	-10000	0	-10000	0	0
Centraspindlin	0.18	0.17	0.34	219	-0.34	1	220
RhoA/GDP	0.015	0.003	-10000	0	-10000	0	0
NSUN2	0.088	0.12	0.27	69	-0.3	17	86
MYLK	0.065	0.077	0.14	236	-0.15	14	250
KIF23	0.087	0.13	0.34	103	-10000	0	103
VIM	0.07	0.092	0.16	241	-10000	0	241
RACGAP1	0.03	0.029	0.34	4	-10000	0	4
mitosis	0	0	-10000	0	-10000	0	0
NCL	0.076	0.12	0.22	24	-0.31	23	47
Chromosomal passenger complex	0.16	0.15	0.29	266	-0.25	3	269
Chromosomal passenger complex/EVI5	0.27	0.22	0.47	260	-10000	0	260
TACC1	0.007	0.062	-10000	0	-0.33	17	17
PPP2R5D	0.02	0.004	-10000	0	-10000	0	0
CUL3	0.021	0.003	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.093	0.18	0.31	6	-0.5	46	52
IHH	-0.016	0.13	0.27	7	-0.38	47	54
SHH Np/Cholesterol/GAS1	-0.036	0.059	0.11	1	-0.18	65	66
LRPAP1	0.021	0.004	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.036	0.058	0.18	65	-0.11	1	66
SMO/beta Arrestin2	-0.15	0.18	0.3	2	-0.33	203	205
SMO	-0.15	0.19	0.34	1	-0.34	214	215
AKT1	-0.082	0.14	0.26	1	-0.48	35	36
ARRB2	0.02	0.006	-10000	0	-10000	0	0
BOC	0.02	0.016	-10000	0	-0.33	1	1
ADRBK1	0.021	0.004	-10000	0	-10000	0	0
heart looping	-0.15	0.18	0.34	1	-0.33	214	215
STIL	-0.089	0.14	0.26	11	-0.32	68	79
DHH N/PTCH2	0.012	0.067	-10000	0	-0.23	36	36
DHH N/PTCH1	-0.11	0.15	-10000	0	-0.36	63	63
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
DHH	-0.004	0.089	-10000	0	-0.33	36	36
PTHLH	-0.13	0.22	0.38	5	-0.57	42	47
determination of left/right symmetry	-0.15	0.18	0.34	1	-0.33	214	215
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
skeletal system development	-0.13	0.22	0.38	5	-0.57	42	47
IHH N/Hhip	-0.22	0.18	0.21	3	-0.32	371	374
DHH N/Hhip	-0.12	0.14	-10000	0	-0.24	280	280
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.15	0.18	0.34	1	-0.33	214	215
pancreas development	-0.16	0.17	-10000	0	-0.32	273	273
HHAT	0.018	0.022	-10000	0	-0.33	2	2
PI3K	0.029	0.014	-10000	0	-0.23	1	1
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	0.012	0.055	-10000	0	-0.33	13	13
somite specification	-0.15	0.18	0.34	1	-0.33	214	215
SHH Np/Cholesterol/PTCH1	-0.1	0.14	0.18	1	-0.34	71	72
SHH Np/Cholesterol/PTCH2	-0.034	0.052	0.11	1	-0.18	60	61
SHH Np/Cholesterol/Megalin	-0.07	0.087	0.11	1	-0.19	161	162
SHH	-0.039	0.07	0.16	1	-0.23	60	61
catabolic process	-0.11	0.16	0.23	2	-0.41	47	49
SMO/Vitamin D3	-0.12	0.18	0.37	2	-0.41	68	70
SHH Np/Cholesterol/Hhip	-0.1	0.1	0.11	1	-0.2	252	253
LRP2	-0.073	0.16	0.32	1	-0.33	139	140
receptor-mediated endocytosis	-0.17	0.19	0.3	2	-0.41	135	137
SHH Np/Cholesterol/BOC	-0.033	0.052	0.11	1	-0.18	59	60
SHH Np/Cholesterol/CDO	-0.035	0.056	0.11	1	-0.18	64	65
mesenchymal cell differentiation	0.1	0.1	0.2	252	-0.11	1	253
mol:Vitamin D3	-0.093	0.15	0.39	5	-0.34	69	74
IHH N/PTCH2	-0.097	0.13	0.21	4	-0.21	279	283
CDON	0.013	0.048	-10000	0	-0.33	10	10
IHH N/PTCH1	-0.1	0.18	0.27	2	-0.39	53	55
Megalin/LRPAP1	-0.038	0.12	0.23	1	-0.23	136	137
PTCH2	0.02	0.016	-10000	0	-0.33	1	1
SHH Np/Cholesterol	-0.029	0.052	-10000	0	-0.17	60	60
PTCH1	-0.11	0.16	0.23	2	-0.41	47	49
HHIP	-0.16	0.17	-10000	0	-0.33	273	273

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.084	0.12	0.23	1	-0.34	51	52
PTK2B	0.017	0.017	-10000	0	-0.33	1	1
mol:Ca2+	-0.13	0.27	-10000	0	-0.89	50	50
EDN1	-0.078	0.14	-10000	0	-0.35	83	83
EDN3	-0.071	0.15	0.32	1	-0.33	132	133
EDN2	0.1	0.14	0.32	139	-0.33	2	141
HRAS/GDP	-0.15	0.19	-10000	0	-0.42	122	122
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.07	0.13	-10000	0	-0.34	69	69
ADCY4	-0.07	0.11	0.22	3	-0.28	62	65
ADCY5	-0.082	0.13	0.28	2	-0.31	79	81
ADCY6	-0.067	0.1	0.22	5	-0.28	52	57
ADCY7	-0.066	0.1	0.24	4	-0.28	52	56
ADCY1	-0.062	0.1	0.21	4	-0.28	49	53
ADCY2	-0.064	0.12	0.21	10	-0.3	57	67
ADCY3	-0.067	0.1	0.26	3	-0.28	53	56
ADCY8	-0.1	0.12	0.25	4	-0.26	122	126
ADCY9	-0.069	0.11	0.22	6	-0.28	60	66
arachidonic acid secretion	-0.12	0.19	-10000	0	-0.49	82	82
ETB receptor/Endothelin-1/Gq/GTP	-0.15	0.16	-10000	0	-0.27	271	271
GNAO1	0.021	0.035	0.32	4	-0.33	2	6
HRAS	0.021	0.004	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	-0.052	0.12	0.31	1	-0.31	45	46
ETA receptor/Endothelin-1/Gs/GTP	-0.055	0.12	0.29	1	-0.29	55	56
mol:GTP	-0.001	0.004	-10000	0	-10000	0	0
COL3A1	-0.054	0.16	0.29	29	-0.34	51	80
EDNRB	-0.16	0.17	-10000	0	-0.33	265	265
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.089	0.13	0.23	1	-0.38	52	53
CYSLTR1	-0.093	0.14	0.23	1	-0.4	52	53
SLC9A1	-0.051	0.081	0.16	1	-0.22	56	57
mol:GDP	-0.16	0.2	-10000	0	-0.44	125	125
SLC9A3	-0.31	0.35	-10000	0	-0.64	208	208
RAF1	-0.15	0.19	-10000	0	-0.47	100	100
JUN	-0.11	0.21	-10000	0	-0.69	41	41
JAK2	-0.08	0.12	0.23	1	-0.34	50	51
mol:IP3	-0.12	0.17	-10000	0	-0.38	113	113
ETA receptor/Endothelin-1	-0.085	0.15	0.35	1	-0.38	56	57
PLCB1	0.018	0.023	0.32	1	-0.33	1	2
PLCB2	0.011	0.047	-10000	0	-0.33	9	9
ETA receptor/Endothelin-3	-0.076	0.11	0.18	1	-0.25	132	133
FOS	-0.14	0.22	-10000	0	-0.68	54	54
Gai/GDP	-0.054	0.21	-10000	0	-0.8	33	33
CRK	0.019	0.006	-10000	0	-10000	0	0
mol:Ca ++	-0.16	0.19	-10000	0	-0.45	121	121
BCAR1	0.02	0.016	-10000	0	-0.32	1	1
PRKCB1	-0.12	0.16	-10000	0	-0.36	118	118
GNAQ	0.015	0.022	-10000	0	-0.33	1	1
GNAZ	-0.006	0.092	-10000	0	-0.33	39	39
GNAL	0.017	0.047	0.32	3	-0.33	7	10
Gs family/GDP	-0.14	0.18	-10000	0	-0.41	118	118
ETA receptor/Endothelin-1/Gq/GTP	-0.072	0.13	-10000	0	-0.32	76	76
MAPK14	-0.14	0.16	0.2	1	-0.34	135	136
TRPC6	-0.14	0.3	-10000	0	-0.97	49	49
GNAI2	0.02	0.004	-10000	0	-10000	0	0
GNAI3	0.02	0.004	-10000	0	-10000	0	0
GNAI1	0.02	0.016	-10000	0	-0.33	1	1
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.14	0.17	-10000	0	-0.34	152	152
ETB receptor/Endothelin-2	-0.074	0.15	0.24	50	-0.21	264	314
ETB receptor/Endothelin-3	-0.16	0.16	0.24	1	-0.27	311	312
ETB receptor/Endothelin-1	-0.16	0.16	0.21	7	-0.3	270	277
MAPK3	-0.15	0.23	-10000	0	-0.63	69	69
MAPK1	-0.16	0.23	-10000	0	-0.63	73	73
Rac1/GDP	-0.14	0.18	-10000	0	-0.42	109	109
cAMP biosynthetic process	-0.078	0.14	0.29	6	-0.36	57	63
MAPK8	-0.12	0.24	-10000	0	-0.69	62	62
SRC	0.02	0.004	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.14	0.14	-10000	0	-0.33	131	131
p130Cas/CRK/Src/PYK2	-0.16	0.22	-10000	0	-0.56	93	93
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.14	0.18	-10000	0	-0.41	113	113
COL1A2	-0.17	0.18	0.31	7	-0.37	170	177
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	0.043	0.12	0.24	71	-0.21	11	82
mol:DAG	-0.12	0.17	-10000	0	-0.38	113	113
MAP2K2	-0.15	0.2	-10000	0	-0.53	81	81
MAP2K1	-0.15	0.2	-10000	0	-0.53	82	82
EDNRA	-0.036	0.076	0.23	1	-0.25	17	18
positive regulation of muscle contraction	-0.059	0.11	0.21	19	-0.3	46	65
Gq family/GDP	-0.11	0.18	0.35	1	-0.41	91	92
HRAS/GTP	-0.14	0.19	-10000	0	-0.44	108	108
PRKCH	-0.12	0.16	-10000	0	-0.38	106	106
RAC1	0.019	0.007	-10000	0	-10000	0	0
PRKCA	-0.12	0.16	-10000	0	-0.37	106	106
PRKCB	-0.13	0.17	-10000	0	-0.4	102	102
PRKCE	-0.13	0.16	-10000	0	-0.39	104	104
PRKCD	-0.12	0.16	-10000	0	-0.39	98	98
PRKCG	-0.12	0.16	-10000	0	-0.36	111	111
regulation of vascular smooth muscle contraction	-0.17	0.26	-10000	0	-0.82	53	53
PRKCQ	-0.14	0.18	-10000	0	-0.39	121	121
PLA2G4A	-0.13	0.21	-10000	0	-0.53	82	82
GNA14	0.009	0.053	-10000	0	-0.33	11	11
GNA15	0.015	0.015	-10000	0	-10000	0	0
GNA12	0.019	0.007	-10000	0	-10000	0	0
GNA11	0.015	0.021	-10000	0	-0.33	1	1
Rac1/GTP	-0.053	0.12	0.31	1	-0.31	46	47
MMP1	0.2	0.17	0.33	255	-0.68	2	257

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.049	0.064	0.12	17	-0.12	226	243
BUB1B	0.071	0.075	0.14	215	-0.13	3	218
PLK1	0.03	0.039	0.092	102	-0.08	2	104
PLK1S1	0.014	0.038	0.11	4	-0.16	15	19
KIF2A	0.023	0.041	0.15	19	-10000	0	19
regulation of mitotic centrosome separation	0.03	0.038	0.092	102	-0.08	2	104
GOLGA2	0.021	0.004	-10000	0	-10000	0	0
Hec1/SPC24	0.17	0.17	0.34	236	-10000	0	236
WEE1	0.029	0.059	0.19	1	-0.28	9	10
cytokinesis	0.086	0.096	0.2	138	-0.2	4	142
PP2A-alpha B56	0.077	0.095	-10000	0	-0.49	6	6
AURKA	0.036	0.057	0.14	101	-0.19	6	107
PICH/PLK1	0.076	0.11	0.21	188	-10000	0	188
CENPE	0.034	0.053	0.13	96	-10000	0	96
RhoA/GTP	0.015	0.003	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.024	0.041	0.15	19	-10000	0	19
PPP2CA	0.02	0.005	-10000	0	-10000	0	0
FZR1	0.02	0.006	-10000	0	-10000	0	0
TPX2	0.073	0.068	0.13	280	-0.16	5	285
PAK1	0.02	0.005	-10000	0	-10000	0	0
SPC24	0.1	0.14	0.32	141	-10000	0	141
FBXW11	0.02	0.005	-10000	0	-10000	0	0
CLSPN	0.059	0.073	0.15	172	-0.23	5	177
GORASP1	0.021	0.004	-10000	0	-10000	0	0
metaphase	0	0.003	0.016	11	-0.011	1	12
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.014	0.019	0.052	42	-0.043	1	43
G2 phase of mitotic cell cycle	0	0.003	0.014	12	-10000	0	12
STAG2	0.021	0.003	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.001	0.098	-10000	0	-0.51	18	18
spindle elongation	0.03	0.038	0.092	102	-0.08	2	104
ODF2	0.021	0.006	-10000	0	-10000	0	0
BUB1	0.066	0.11	-10000	0	-0.51	7	7
TPT1	0.01	0.043	0.11	2	-0.16	26	28
CDC25C	0.098	0.097	0.16	316	-0.22	18	334
CDC25B	0.022	0.011	-10000	0	-10000	0	0
SGOL1	0.049	0.064	0.12	226	-0.12	17	243
RHOA	0.02	0.004	-10000	0	-10000	0	0
CCNB1/CDK1	0.074	0.085	0.22	127	-10000	0	127
CDC14B	-0.008	0.004	-10000	0	-10000	0	0
CDC20	0.2	0.15	0.32	294	-10000	0	294
PLK1/PBIP1	0.01	0.041	0.14	38	-10000	0	38
mitosis	-0.003	0.006	0.021	8	-0.016	72	80
FBXO5	0.014	0.039	0.11	15	-0.1	2	17
CDC2	0.003	0.005	0.011	130	-0.01	6	136
NDC80	0.15	0.15	0.32	225	-10000	0	225
metaphase plate congression	0.022	0.041	-10000	0	-0.22	9	9
ERCC6L	0.078	0.1	0.22	163	-10000	0	163
NLP/gamma Tubulin	0.016	0.022	0.076	19	-0.085	3	22
microtubule cytoskeleton organization	0.01	0.043	0.11	2	-0.16	26	28
G2/M transition DNA damage checkpoint	-0.001	0.002	0.012	2	-10000	0	2
PPP1R12A	0.021	0.004	-10000	0	-10000	0	0
interphase	-0.001	0.002	0.012	2	-10000	0	2
PLK1/PRC1-2	0.16	0.15	0.29	262	-10000	0	262
GRASP65/GM130/RAB1/GTP/PLK1	0.051	0.03	-10000	0	-10000	0	0
RAB1A	0.021	0.001	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.024	0.035	0.082	101	-0.07	2	103
mitotic prometaphase	0.001	0.003	0.018	9	-10000	0	9
proteasomal ubiquitin-dependent protein catabolic process	0.047	0.056	0.2	2	-0.39	1	3
microtubule-based process	0.14	0.12	0.25	265	-10000	0	265
Golgi organization	0.03	0.038	0.092	102	-0.08	2	104
Cohesin/SA2	0.036	0.031	0.12	8	-10000	0	8
PPP1CB/MYPT1	0.031	0.007	-10000	0	-10000	0	0
KIF20A	0.18	0.15	0.32	265	-10000	0	265
APC/C/CDC20	0.15	0.12	0.25	295	-10000	0	295
PPP2R1A	0.021	0.004	-10000	0	-10000	0	0
chromosome segregation	0.01	0.04	0.14	38	-10000	0	38
PRC1	0.062	0.1	0.32	70	-10000	0	70
ECT2	0.031	0.058	0.18	47	-10000	0	47
C13orf34	0.024	0.032	0.077	102	-0.067	2	104
NUDC	0.022	0.041	-10000	0	-0.22	9	9
regulation of attachment of spindle microtubules to kinetochore	0.07	0.075	0.14	215	-0.13	3	218
spindle assembly	0.023	0.031	0.089	40	-0.07	2	42
spindle stabilization	0.014	0.037	0.11	3	-0.16	15	18
APC/C/HCDH1	0.016	0.006	-10000	0	-10000	0	0
MKLP2/PLK1	0.14	0.12	0.25	265	-10000	0	265
CCNB1	0.1	0.14	0.32	137	-10000	0	137
PPP1CB	0.022	0.003	-10000	0	-10000	0	0
BTRC	0.021	0.003	-10000	0	-10000	0	0
ROCK2	0.025	0.038	0.17	2	-0.19	1	3
TUBG1	0.018	0.026	0.12	3	-0.2	3	6
G2/M transition of mitotic cell cycle	0.03	0.056	0.13	73	-10000	0	73
MLF1IP	0.005	0.043	0.16	35	-10000	0	35
INCENP	0.021	0.004	-10000	0	-10000	0	0

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.021	0.003	-10000	0	-10000	0	0
Aurora C/Aurora B/INCENP	0.12	0.094	0.21	239	-0.16	3	242
metaphase	0	0	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
H3F3B	0.016	0.014	-10000	0	-10000	0	0
AURKB	0.16	0.15	0.32	247	-10000	0	247
AURKC	0.02	0.035	0.32	3	-0.33	3	6

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.038	0.049	0.2	29	-0.16	10	39
RGS9BP	-0.03	0.12	-10000	0	-0.33	73	73
mol:GTP	0	0	-10000	0	-10000	0	0
GRK1	0.037	0.074	0.32	32	-10000	0	32
mol:Na +	0.11	0.11	0.23	201	-10000	0	201
mol:ADP	-0.005	0.044	0.16	33	-10000	0	33
GNAT2	0.02	0.014	0.32	1	-10000	0	1
RGS9-1/Gbeta5/R9AP	-0.058	0.13	-10000	0	-0.21	193	193
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.024	0.014	0.21	2	-10000	0	2
GRK7	0.02	0.003	-10000	0	-10000	0	0
CNGB3	0.063	0.11	0.32	77	-10000	0	77
Cone Metarhodopsin II/X-Arrestin	0.015	0.016	0.22	3	-10000	0	3
mol:Ca2+	0.056	0.09	0.21	103	-10000	0	103
Cone PDE6	-0.039	0.12	-10000	0	-0.19	182	182
Cone Metarhodopsin II	0.034	0.042	0.2	31	-10000	0	31
Na + (4 Units)	0.11	0.12	0.24	204	-10000	0	204
GNAT2/GDP	-0.044	0.11	-10000	0	-0.18	192	192
GNB5	0.021	0.004	-10000	0	-10000	0	0
mol:GMP (4 units)	-0.015	0.019	0.17	4	-10000	0	4
Cone Transducin	0.042	0.053	0.21	29	-0.18	10	39
SLC24A2	0.041	0.08	0.32	38	-10000	0	38
GNB3/GNGT2	0.036	0.061	0.23	29	-0.23	10	39
GNB3	0.037	0.073	0.32	30	-0.33	1	31
GNAT2/GTP	0.015	0.01	0.22	1	-10000	0	1
CNGA3	0.12	0.14	0.32	173	-10000	0	173
ARR3	0.02	0.023	0.32	3	-10000	0	3
absorption of light	0	0	-10000	0	-10000	0	0
cGMP/Cone CNG Channel	0.11	0.11	0.24	201	-10000	0	201
mol:Pi	-0.058	0.13	-10000	0	-0.21	193	193
Cone CNG Channel	0.093	0.091	0.21	175	-10000	0	175
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	0.041	0.08	0.32	38	-10000	0	38
RGS9	-0.081	0.16	-10000	0	-0.33	149	149
PDE6C	0.018	0.003	-10000	0	-10000	0	0
GNGT2	0.014	0.048	-10000	0	-0.33	10	10
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	0.018	0.014	0.32	1	-10000	0	1

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.085	0.26	-10000	0	-0.86	46	46
MKNK1	0.021	0.002	-10000	0	-10000	0	0
MAPK14	-0.023	0.12	-10000	0	-0.3	78	78
ATF2/c-Jun	-0.035	0.1	-10000	0	-0.36	20	20
MAPK11	-0.022	0.12	-10000	0	-0.31	74	74
MITF	-0.047	0.15	-10000	0	-0.37	84	84
MAPKAPK5	-0.039	0.14	-10000	0	-0.35	76	76
KRT8	-0.04	0.14	0.27	2	-0.35	80	82
MAPKAPK3	0.02	0.004	-10000	0	-10000	0	0
MAPKAPK2	0.019	0.006	-10000	0	-10000	0	0
p38alpha-beta/CK2	-0.037	0.17	-10000	0	-0.42	81	81
CEBPB	-0.039	0.14	-10000	0	-0.36	73	73
SLC9A1	-0.041	0.14	-10000	0	-0.36	77	77
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	-0.04	0.14	0.25	1	-0.35	79	80
p38alpha-beta/MNK1	-0.017	0.15	-10000	0	-0.36	71	71
JUN	-0.034	0.1	-10000	0	-0.36	20	20
PPARGC1A	-0.1	0.19	-10000	0	-0.34	169	169
USF1	-0.033	0.13	0.32	1	-0.35	67	68
RAB5/GDP/GDI1	-0.028	0.1	-10000	0	-0.26	77	77
NOS2	-0.085	0.27	0.4	2	-0.86	48	50
DDIT3	-0.039	0.14	0.23	2	-0.35	77	79
RAB5A	0.02	0.004	-10000	0	-10000	0	0
HSPB1	-0.039	0.12	0.26	10	-0.3	72	82
p38alpha-beta/HBP1	-0.017	0.15	-10000	0	-0.36	70	70
CREB1	-0.046	0.15	0.24	2	-0.38	80	82
RAB5/GDP	0.015	0.003	-10000	0	-10000	0	0
EIF4E	-0.059	0.12	0.18	1	-0.33	70	71
RPS6KA4	-0.041	0.14	-10000	0	-0.36	79	79
PLA2G4A	-0.035	0.13	0.2	13	-0.32	67	80
GDI1	-0.039	0.13	0.28	1	-0.35	76	77
TP53	-0.066	0.16	0.26	1	-0.44	74	75
RPS6KA5	-0.041	0.14	0.3	3	-0.36	78	81
ESR1	-0.044	0.15	0.28	1	-0.38	78	79
HBP1	0.02	0.005	-10000	0	-10000	0	0
MEF2C	-0.04	0.14	-10000	0	-0.36	77	77
MEF2A	-0.041	0.14	-10000	0	-0.36	78	78
EIF4EBP1	-0.048	0.16	0.24	2	-0.4	79	81
KRT19	-0.041	0.14	-10000	0	-0.36	77	77
ELK4	-0.037	0.13	-10000	0	-0.35	74	74
ATF6	-0.034	0.13	0.32	1	-0.35	68	69
ATF1	-0.046	0.15	0.24	3	-0.38	81	84
p38alpha-beta/MAPKAPK2	-0.017	0.14	-10000	0	-0.36	70	70
p38alpha-beta/MAPKAPK3	-0.018	0.15	-10000	0	-0.36	73	73

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.018	0.29	0.53	39	-0.65	19	58
PCK1	0.066	0.24	0.57	52	-0.59	2	54
HNF4A	-0.094	0.47	0.68	60	-0.78	103	163
KCNJ11	0.026	0.29	0.6	38	-0.77	12	50
AKT1	0.047	0.18	0.41	51	-0.4	1	52
response to starvation	-0.027	0.075	0.15	4	-0.21	40	44
DLK1	0.047	0.29	0.59	51	-0.7	5	56
NKX2-1	0.03	0.17	0.39	45	-0.43	5	50
ACADM	-0.02	0.28	0.53	34	-0.65	20	54
TAT	0.059	0.23	0.54	55	-0.48	3	58
CEBPB	0.027	0.02	-10000	0	-10000	0	0
CEBPA	0.015	0.078	0.21	4	-0.32	22	26
TTR	0.068	0.28	0.62	59	-0.7	10	69
PKLR	0.009	0.3	0.6	41	-0.65	19	60
APOA1	-0.2	0.61	0.73	51	-1.1	138	189
CPT1C	-0.017	0.29	0.53	42	-0.64	20	62
ALAS1	0.036	0.18	0.47	22	-0.54	2	24
TFRC	0.093	0.3	0.64	62	-0.88	8	70
FOXF1	-0.049	0.14	-10000	0	-0.33	102	102
NF1	0.022	0.004	-10000	0	-10000	0	0
HNF1A (dimer)	0.11	0.16	0.39	111	-0.32	1	112
CPT1A	-0.016	0.29	0.52	42	-0.64	20	62
HMGCS1	0.009	0.29	0.59	40	-0.66	16	56
NR3C1	0.045	0.048	0.22	12	-10000	0	12
CPT1B	-0.02	0.29	0.52	42	-0.64	21	63
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.042	0.041	-10000	0	-10000	0	0
GCK	-0.011	0.3	0.55	43	-0.67	23	66
CREB1	0.036	0.037	0.18	6	-10000	0	6
IGFBP1	0.033	0.21	0.53	36	-0.66	2	38
PDX1	0.11	0.28	0.68	66	-0.54	1	67
UCP2	-0.015	0.29	0.52	42	-0.65	20	62
ALDOB	0.044	0.3	0.65	48	-0.77	7	55
AFP	0.078	0.1	0.36	26	-10000	0	26
BDH1	-0.019	0.29	0.53	42	-0.64	21	63
HADH	0.028	0.27	0.57	38	-0.7	5	43
F2	-0.011	0.42	0.8	54	-0.86	20	74
HNF1A	0.11	0.16	0.39	111	-0.33	1	112
G6PC	0.083	0.13	0.52	15	-10000	0	15
SLC2A2	0.091	0.28	0.66	64	-0.67	3	67
INS	-0.032	0.035	-10000	0	-10000	0	0
FOXA1	0.057	0.078	0.27	39	-0.32	1	40
FOXA3	0.16	0.18	0.42	143	-0.29	3	146
FOXA2	0.071	0.38	0.82	60	-0.77	6	66
ABCC8	-0.013	0.37	0.62	41	-0.79	52	93
ALB	0.09	0.12	0.33	64	-10000	0	64

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.006	0.058	-10000	0	-0.35	11	11
Crk/p130 Cas/Paxillin	-0.056	0.086	-10000	0	-0.23	76	76
JUN	-0.034	0.088	0.16	8	-0.19	97	105
HRAS	0.021	0.004	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	0.012	0.11	0.23	43	-0.18	86	129
RAP1A	0.02	0.004	-10000	0	-10000	0	0
FRS2	0.02	0.005	-10000	0	-10000	0	0
RAP1A/GDP	0.015	0.003	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	0.009	0.12	0.23	46	-0.18	111	157
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.021	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.019	0.006	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.014	0.088	0.21	5	-0.17	112	117
RHOA	0.02	0.004	-10000	0	-10000	0	0
RAP1A/GTP	0.007	0.1	0.19	46	-0.17	94	140
GRB7	0.019	0.022	-10000	0	-0.33	2	2
RET51/GFRalpha1/GDNF	0.008	0.11	0.23	45	-0.17	111	156
MAPKKK cascade	-0.031	0.093	0.18	6	-0.2	89	95
BCAR1	0.02	0.016	-10000	0	-0.33	1	1
RET9/GFRalpha1/GDNF/IRS1	-0.013	0.089	0.21	6	-0.17	112	118
lamellipodium assembly	-0.034	0.088	-10000	0	-0.22	66	66
RET51/GFRalpha1/GDNF/SHC	0.012	0.11	0.23	42	-0.18	78	120
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.008	0.08	0.21	5	-0.17	89	94
RET9/GFRalpha1/GDNF/Shank3	-0.014	0.09	0.21	6	-0.18	113	119
MAPK3	-0.019	0.1	0.28	12	-0.3	1	13
DOK1	0.021	0.002	-10000	0	-10000	0	0
DOK6	-0.01	0.096	-10000	0	-0.33	43	43
PXN	0.021	0.003	-10000	0	-10000	0	0
neurite development	-0.029	0.094	0.23	7	-0.24	21	28
DOK5	0.059	0.1	0.32	67	-10000	0	67
GFRA1	-0.076	0.16	0.32	1	-0.33	144	145
MAPK8	-0.036	0.087	0.15	7	-0.19	100	107
HRAS/GTP	-0.004	0.12	0.34	2	-0.21	95	97
tube development	-0.012	0.087	0.2	13	-0.17	105	118
MAPK1	-0.02	0.095	0.26	10	-0.3	1	11
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.029	0.081	-10000	0	-0.19	98	98
Rac1/GDP	0.014	0.005	-10000	0	-10000	0	0
SRC	0.02	0.004	-10000	0	-10000	0	0
PDLIM7	0.02	0.005	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.003	0.13	0.23	40	-0.2	114	154
SHC1	0.018	0.016	0.32	1	-10000	0	1
RET51/GFRalpha1/GDNF/Dok4	0.01	0.11	0.23	47	-0.18	108	155
RET51/GFRalpha1/GDNF/Dok5	0.023	0.12	0.24	72	-0.17	100	172
PRKCA	0.019	0.022	-10000	0	-0.33	2	2
HRAS/GDP	0.015	0.003	-10000	0	-10000	0	0
CREB1	-0.022	0.091	0.23	1	-0.22	73	74
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.024	0.078	0.16	2	-0.2	83	85
RET51/GFRalpha1/GDNF/Grb7	0.009	0.12	0.23	45	-0.18	97	142
mol:GDP	0	0	-10000	0	-10000	0	0
RET	0.059	0.11	0.32	68	-0.33	3	71
DOK4	0.02	0.004	-10000	0	-10000	0	0
JNK cascade	-0.032	0.089	0.24	2	-0.18	97	99
RET9/GFRalpha1/GDNF/FRS2	-0.012	0.087	0.21	6	-0.18	106	112
SHANK3	0.018	0.027	-10000	0	-0.33	3	3
RASA1	0.02	0.005	-10000	0	-10000	0	0
NCK1	0.021	0.003	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.023	0.075	0.16	2	-0.19	82	84
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.02	0.093	0.18	10	-0.19	91	101
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.023	0.097	0.18	7	-0.2	101	108
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.011	0.087	0.19	11	-0.19	73	84
PI3K	-0.043	0.13	0.25	5	-0.3	77	82
SOS1	0.021	0.003	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.006	0.089	0.21	6	-0.17	105	111
GRB10	0.019	0.006	-10000	0	-10000	0	0
activation of MAPKK activity	-0.022	0.083	0.17	1	-0.26	5	6
RET51/GFRalpha1/GDNF/FRS2	0.009	0.11	0.23	44	-0.17	109	153
GAB1	0.02	0.022	-10000	0	-0.33	2	2
IRS1	0.02	0.016	-10000	0	-0.33	1	1
IRS2	0.019	0.016	-10000	0	-0.33	1	1
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.013	0.09	0.19	11	-0.2	76	87
RET51/GFRalpha1/GDNF/PKC alpha	0.009	0.11	0.23	45	-0.18	95	140
GRB2	0.02	0.004	-10000	0	-10000	0	0
PRKACA	0.02	0.005	-10000	0	-10000	0	0
GDNF	0.02	0.037	0.32	7	-10000	0	7
RAC1	0.019	0.007	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	0.009	0.12	0.23	46	-0.18	112	158
Rac1/GTP	-0.032	0.11	0.22	1	-0.25	66	67
RET9/GFRalpha1/GDNF	-0.023	0.091	0.21	6	-0.19	112	118
GFRalpha1/GDNF	-0.03	0.11	0.23	6	-0.23	112	118

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.02	0.014	0.32	1	-10000	0	1
LAT2	-0.072	0.13	-10000	0	-0.32	84	84
AP1	-0.079	0.2	-10000	0	-0.45	85	85
mol:PIP3	-0.081	0.17	0.28	20	-0.36	99	119
IKBKB	-0.033	0.12	0.24	30	-0.23	63	93
AKT1	-0.038	0.14	0.31	49	-0.27	45	94
IKBKG	-0.042	0.11	0.21	25	-0.22	72	97
MS4A2	-0.06	0.14	-10000	0	-0.32	111	111
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.02	0.006	-10000	0	-10000	0	0
MAP3K1	-0.066	0.14	0.22	9	-0.35	69	78
mol:Ca2+	-0.06	0.14	0.22	34	-0.28	95	129
LYN	0.014	0.018	-10000	0	-10000	0	0
CBLB	-0.073	0.12	-10000	0	-0.31	87	87
SHC1	0.019	0.016	0.32	1	-10000	0	1
RasGAP/p62DOK	0.02	0.059	-10000	0	-0.18	42	42
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	0.019	0.027	-10000	0	-0.33	3	3
PLD2	-0.044	0.15	0.28	55	-0.24	110	165
PTPN13	-0.088	0.17	-10000	0	-0.51	28	28
PTPN11	0.011	0.024	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	-0.048	0.12	0.27	14	-0.28	43	57
SYK	0.014	0.027	-10000	0	-0.33	2	2
GRB2	0.02	0.004	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.085	0.16	0.18	1	-0.35	103	104
LAT	-0.073	0.13	-10000	0	-0.31	87	87
PAK2	-0.072	0.16	0.24	8	-0.38	74	82
NFATC2	-0.036	0.1	-10000	0	-0.51	18	18
HRAS	-0.074	0.17	0.25	8	-0.38	91	99
GAB2	0.017	0.034	-10000	0	-0.33	5	5
PLA2G1B	-0.052	0.17	-10000	0	-0.92	18	18
Fc epsilon R1	-0.054	0.14	0.22	1	-0.26	157	158
Antigen/IgE/Fc epsilon R1	-0.047	0.13	0.21	1	-0.23	156	157
mol:GDP	-0.088	0.18	-10000	0	-0.45	75	75
JUN	0.019	0.027	-10000	0	-0.33	3	3
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.019	0.017	-10000	0	-0.33	1	1
FOS	0.002	0.078	-10000	0	-0.33	27	27
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.069	0.14	-10000	0	-0.32	92	92
CHUK	-0.047	0.11	0.21	22	-0.23	72	94
KLRG1	-0.064	0.11	0.14	1	-0.28	83	84
VAV1	-0.069	0.12	-10000	0	-0.32	81	81
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.071	0.12	-10000	0	-0.31	86	86
negative regulation of mast cell degranulation	-0.056	0.12	-10000	0	-0.31	58	58
BTK	-0.095	0.2	-10000	0	-0.49	77	77
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.079	0.15	-10000	0	-0.31	125	125
GAB2/PI3K/SHP2	-0.078	0.086	-10000	0	-0.23	106	106
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.065	0.13	-10000	0	-0.27	116	116
RAF1	-0.016	0.18	-10000	0	-0.96	18	18
Fc epsilon R1/FcgammaRIIB/SHIP	-0.033	0.14	0.22	1	-0.23	152	153
FCER1G	0.011	0.044	-10000	0	-0.33	7	7
FCER1A	-0.067	0.15	0.32	1	-0.34	119	120
Antigen/IgE/Fc epsilon R1/Fyn	-0.04	0.12	0.21	1	-0.22	153	154
MAPK3	-0.018	0.17	-10000	0	-0.88	18	18
MAPK1	-0.022	0.17	-10000	0	-0.91	18	18
NFKB1	0.021	0.003	-10000	0	-10000	0	0
MAPK8	-0.065	0.22	-10000	0	-0.67	48	48
DUSP1	-0.008	0.095	-10000	0	-0.33	42	42
NF-kappa-B/RelA	-0.032	0.062	0.13	6	-0.15	48	54
actin cytoskeleton reorganization	-0.073	0.16	-10000	0	-0.51	18	18
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.065	0.15	-10000	0	-0.38	66	66
FER	-0.071	0.12	-10000	0	-0.31	85	85
RELA	0.021	0.004	-10000	0	-10000	0	0
ITK	-0.024	0.067	-10000	0	-0.31	19	19
SOS1	0.021	0.003	-10000	0	-10000	0	0
PLCG1	-0.089	0.18	0.23	6	-0.4	97	103
cytokine secretion	-0.029	0.038	-10000	0	-0.15	3	3
SPHK1	-0.07	0.12	-10000	0	-0.31	84	84
PTK2	-0.076	0.16	-10000	0	-0.54	18	18
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.085	0.16	0.22	1	-0.36	104	105
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	-0.078	0.17	0.24	34	-0.34	102	136
MAP2K2	-0.022	0.17	-10000	0	-0.9	18	18
MAP2K1	-0.021	0.17	-10000	0	-0.9	18	18
MAP2K7	0.02	0.005	-10000	0	-10000	0	0
KLRG1/SHP2	-0.05	0.11	0.17	1	-0.28	60	61
MAP2K4	-0.091	0.32	-10000	0	-0.92	63	63
Fc epsilon R1/FcgammaRIIB	-0.04	0.14	0.22	1	-0.23	155	156
mol:Choline	-0.044	0.15	0.28	55	-0.23	110	165
SHC/Grb2/SOS1	-0.042	0.13	-10000	0	-0.3	76	76
FYN	0.019	0.016	-10000	0	-0.33	1	1
DOK1	0.021	0.002	-10000	0	-10000	0	0
PXN	-0.074	0.15	-10000	0	-0.5	18	18
HCLS1	-0.073	0.13	-10000	0	-0.32	86	86
PRKCB	-0.062	0.14	0.24	22	-0.3	83	105
FCGR2B	0.019	0.007	-10000	0	-10000	0	0
IGHE	-0.001	0.008	-10000	0	-10000	0	0
KLRG1/SHIP	-0.057	0.12	-10000	0	-0.32	58	58
LCP2	0.018	0.027	-10000	0	-0.32	3	3
PLA2G4A	-0.066	0.12	-10000	0	-0.31	81	81
RASA1	0.02	0.005	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.044	0.15	0.28	55	-0.23	110	165
IKK complex	-0.024	0.097	0.22	30	-0.18	48	78
WIPF1	0.021	0.003	-10000	0	-10000	0	0

BMP receptor 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	0.021	0.11	0.24	29	-0.18	86	115
SMAD6-7/SMURF1	0.009	0.076	-10000	0	-0.2	58	58
NOG	0.011	0.087	0.32	11	-0.33	24	35
SMAD9	-0.11	0.22	-10000	0	-0.46	138	138
SMAD4	0.019	0.007	-10000	0	-10000	0	0
SMAD5	-0.038	0.1	-10000	0	-0.34	34	34
BMP7/USAG1	-0.13	0.14	0.23	8	-0.24	292	300
SMAD5/SKI	-0.031	0.12	0.26	3	-0.36	32	35
SMAD1	-0.003	0.057	-10000	0	-0.26	13	13
BMP2	-0.024	0.12	-10000	0	-0.33	66	66
SMAD1/SMAD1/SMAD4	-0.009	0.075	-10000	0	-0.3	10	10
BMPR1A	0.021	0.003	-10000	0	-10000	0	0
BMPR1B	-0.011	0.11	0.32	3	-0.33	50	53
BMPR1A-1B/BAMBI	0.022	0.081	0.22	15	-0.2	50	65
AHSG	0.038	0.075	0.32	33	-10000	0	33
CER1	0.02	0.031	0.32	5	-10000	0	5
BMP2-4/CER1	0.003	0.085	0.22	3	-0.2	70	73
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.03	0.1	-10000	0	-0.33	34	34
BMP2-4 (homodimer)	-0.009	0.095	-10000	0	-0.24	72	72
RGMB	0.02	0.005	-10000	0	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	0.001	0.11	0.23	3	-0.2	101	104
RGMA	0.023	0.039	0.32	6	-0.33	2	8
SMURF1	0.02	0.005	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.024	0.085	-10000	0	-0.29	25	25
BMP2-4/USAG1	-0.12	0.14	-10000	0	-0.22	300	300
SMAD6/SMURF1/SMAD5	-0.029	0.12	0.26	3	-0.37	28	31
SOSTDC1	-0.19	0.17	-10000	0	-0.33	302	302
BMP7/BMPR2/BMPR1A-1B	0.015	0.097	0.23	14	-0.19	80	94
SKI	0.021	0.004	-10000	0	-10000	0	0
BMP6 (homodimer)	-0.026	0.12	0.32	2	-0.32	71	73
HFE2	0.022	0.041	0.32	9	-10000	0	9
ZFYVE16	0.02	0.005	-10000	0	-10000	0	0
MAP3K7	0.019	0.006	-10000	0	-10000	0	0
BMP2-4/CHRD	0.013	0.091	0.22	18	-0.2	68	86
SMAD5/SMAD5/SMAD4	-0.03	0.12	0.26	3	-0.38	27	30
MAPK1	0.02	0.005	-10000	0	-10000	0	0
TAK1/TAB family	-0.01	0.09	-10000	0	-0.27	25	25
BMP7 (homodimer)	0	0.11	0.32	17	-0.32	44	61
NUP214	0.021	0.004	-10000	0	-10000	0	0
BMP6/FETUA	0.008	0.1	0.23	33	-0.23	66	99
SMAD1/SKI	0.008	0.067	0.23	1	-0.29	10	11
SMAD6	-0.023	0.12	-10000	0	-0.33	64	64
CTDSP2	0.02	0.005	-10000	0	-10000	0	0
BMP2-4/FETUA	0.016	0.096	0.22	29	-0.2	68	97
MAP3K7IP1	0	0	-10000	0	-10000	0	0
GREM1	0.22	0.15	0.32	334	-10000	0	334
BMPR2 (homodimer)	0.021	0.003	-10000	0	-10000	0	0
GADD34/PP1CA	0.038	0.02	-10000	0	-0.2	2	2
BMPR1A-1B (homodimer)	0.007	0.078	0.23	3	-0.23	49	52
CHRDL1	-0.1	0.17	-10000	0	-0.33	184	184
ENDOFIN/SMAD1	0.007	0.065	0.23	1	-0.29	9	10
SMAD6-7/SMURF1/SMAD1	0	0.086	-10000	0	-0.35	8	8
SMAD6/SMURF1	0.02	0.005	-10000	0	-10000	0	0
BAMBI	0.026	0.062	0.32	15	-0.33	5	20
SMURF2	0.021	0.004	-10000	0	-10000	0	0
BMP2-4/CHRDL1	-0.07	0.14	-10000	0	-0.24	202	202
BMP2-4/GREM1	0.1	0.14	0.22	267	-0.16	70	337
SMAD7	0.018	0.017	-10000	0	-0.33	1	1
SMAD8A/SMAD8A/SMAD4	-0.11	0.21	-10000	0	-0.43	143	143
SMAD1/SMAD6	0.007	0.068	0.23	1	-0.3	10	11
TAK1/SMAD6	0.027	0.011	-10000	0	-10000	0	0
BMP7	0	0.11	0.32	17	-0.33	44	61
BMP6	-0.026	0.12	0.32	2	-0.33	71	73
MAP3K7IP2	0	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.029	0.093	-10000	0	-0.32	30	30
PPM1A	0.021	0.004	-10000	0	-10000	0	0
SMAD1/SMURF2	0.006	0.068	0.23	1	-0.29	10	11
SMAD7/SMURF1	0.026	0.016	-10000	0	-0.23	1	1
CTDSPL	0.021	0.004	-10000	0	-10000	0	0
PPP1CA	0.021	0.004	-10000	0	-10000	0	0
XIAP	0.021	0.003	-10000	0	-10000	0	0
CTDSP1	0.021	0.002	-10000	0	-10000	0	0
PPP1R15A	0.019	0.022	-10000	0	-0.33	2	2
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.027	0.1	0.22	1	-0.33	31	32
CHRD	0.033	0.065	0.32	23	-0.33	1	24
BMPR2	0.021	0.003	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.03	0.09	-10000	0	-0.31	26	26
BMP4	0.014	0.058	0.32	3	-0.33	12	15
FST	0.025	0.09	0.32	25	-0.33	15	40
BMP2-4/NOG	-0.001	0.1	0.22	7	-0.22	82	89
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	0.023	0.093	-10000	0	-0.18	72	72

Osteopontin-mediated 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.074	0.078	0.2	79	-10000	0	79
NF kappa B1 p50/RelA/I kappa B alpha	0.082	0.091	0.29	25	-10000	0	25
alphaV/beta3 Integrin/Osteopontin/Src	0.18	0.099	0.24	347	-10000	0	347
AP1	0.09	0.096	0.33	17	-10000	0	17
ILK	0.065	0.069	0.24	22	-10000	0	22
bone resorption	0.043	0.072	0.23	17	-10000	0	17
PTK2B	0.017	0.017	-10000	0	-0.33	1	1
PYK2/p130Cas	0.14	0.11	0.28	77	-10000	0	77
ITGAV	0.026	0.008	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.027	0.029	-10000	0	-0.23	6	6
alphaV/beta3 Integrin/Osteopontin	0.18	0.11	0.25	341	-0.19	4	345
MAP3K1	0.064	0.068	0.21	32	-0.18	4	36
JUN	0.019	0.027	-10000	0	-0.33	3	3
MAPK3	0.06	0.082	0.22	81	-10000	0	81
MAPK1	0.059	0.081	0.22	77	-10000	0	77
Rac1/GDP	0.014	0.005	-10000	0	-10000	0	0
NFKB1	0.021	0.003	-10000	0	-10000	0	0
MAPK8	0.044	0.06	0.22	21	-10000	0	21
ITGB3	0.035	0.074	0.34	23	-0.32	5	28
NFKBIA	0.055	0.084	0.22	78	-10000	0	78
FOS	0.003	0.077	-10000	0	-0.32	27	27
CD44	0.015	0.046	-10000	0	-0.33	9	9
CHUK	0.021	0.003	-10000	0	-10000	0	0
PLAU	0.087	0.13	0.35	77	-10000	0	77
NF kappa B1 p50/RelA	0.086	0.1	0.27	75	-10000	0	75
BCAR1	0.02	0.016	-10000	0	-0.33	1	1
RELA	0.021	0.004	-10000	0	-10000	0	0
alphaV beta3 Integrin	0.046	0.055	0.26	23	-0.23	5	28
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	0.063	0.068	0.21	33	-0.18	1	34
VAV3	0.041	0.062	0.2	23	-0.29	2	25
MAP3K14	0.073	0.078	0.21	80	-10000	0	80
ROCK2	0.021	0.003	-10000	0	-10000	0	0
SPP1	0.23	0.14	0.33	351	-10000	0	351
RAC1	0.019	0.007	-10000	0	-10000	0	0
Rac1/GTP	0.037	0.059	0.18	20	-0.26	2	22
MMP2	0.034	0.075	0.3	8	-10000	0	8

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	0.007	0.076	0.22	1	-0.29	19	20
alphaM/beta2 Integrin/GPIbA	0.005	0.081	0.22	3	-0.28	25	28
alphaM/beta2 Integrin/proMMP-9	0.048	0.11	0.22	104	-0.26	17	121
PLAUR	0.02	0.004	-10000	0	-10000	0	0
HMGB1	0.005	0.03	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Talin	0.007	0.077	-10000	0	-0.3	19	19
AGER	-0.29	0.12	-10000	0	-0.34	444	444
RAP1A	0.02	0.004	-10000	0	-10000	0	0
SELPLG	0.009	0.062	-10000	0	-0.33	17	17
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.19	0.12	-10000	0	-0.23	424	424
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	0.084	0.12	0.32	109	-10000	0	109
CYR61	0.005	0.072	-10000	0	-0.33	23	23
TLN1	0.019	0.016	-10000	0	-0.33	1	1
Rap1/GTP	-0.05	0.14	-10000	0	-0.36	51	51
RHOA	0.02	0.004	-10000	0	-10000	0	0
P-selectin oligomer	-0.049	0.14	-10000	0	-0.32	101	101
MYH2	-0.1	0.16	0.22	2	-0.39	82	84
MST1R	0.02	0.016	-10000	0	-0.33	1	1
leukocyte activation during inflammatory response	0.007	0.086	0.19	20	-0.21	42	62
APOB	0.018	0.1	0.32	24	-0.33	25	49
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	0.021	0.014	0.32	1	-10000	0	1
JAM3	0.019	0.022	-10000	0	-0.33	2	2
GP1BA	0.017	0.047	0.32	3	-0.33	7	10
alphaM/beta2 Integrin/CTGF	-0.001	0.087	-10000	0	-0.26	36	36
alphaM/beta2 Integrin	-0.066	0.15	0.21	2	-0.38	58	60
JAM3 homodimer	0.019	0.022	-10000	0	-0.32	2	2
ICAM2	0.018	0.027	-10000	0	-0.33	3	3
ICAM1	0.017	0.034	-10000	0	-0.33	5	5
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.066	0.14	0.21	2	-0.38	58	60
cell adhesion	0.005	0.081	0.22	3	-0.28	25	28
NFKB1	-0.22	0.17	-10000	0	-0.47	128	128
THY1	0.028	0.048	0.32	13	-10000	0	13
RhoA/GDP	0.015	0.003	-10000	0	-10000	0	0
Lipoprotein(a)	0.022	0.063	0.21	25	-0.19	26	51
alphaM/beta2 Integrin/LRP/tPA	0.033	0.096	0.22	42	-0.29	18	60
IL6	-0.24	0.25	-10000	0	-0.65	124	124
ITGB2	-0.001	0.057	-10000	0	-0.35	10	10
elevation of cytosolic calcium ion concentration	0.044	0.1	0.22	74	-0.28	16	90
alphaM/beta2 Integrin/JAM2/JAM3	-0.003	0.1	-10000	0	-0.24	56	56
JAM2	-0.013	0.1	-10000	0	-0.33	49	49
alphaM/beta2 Integrin/ICAM1	0.024	0.086	0.22	12	-0.27	19	31
alphaM/beta2 Integrin/uPA/Plg	0.047	0.11	0.23	80	-0.27	18	98
RhoA/GTP	-0.078	0.16	0.23	2	-0.42	58	60
positive regulation of phagocytosis	-0.053	0.13	-10000	0	-0.36	50	50
Ron/MSP	0.037	0.042	0.23	19	-0.23	2	21
alphaM/beta2 Integrin/uPAR/uPA	0.046	0.1	0.23	74	-0.28	16	90
alphaM/beta2 Integrin/uPAR	0.008	0.073	-10000	0	-0.3	17	17
PLAU	0.075	0.12	0.32	91	-10000	0	91
PLAT	0.047	0.092	0.32	49	-0.33	1	50
actin filament polymerization	-0.1	0.15	0.21	2	-0.38	83	85
MST1	0.031	0.06	0.32	19	-0.33	1	20
alphaM/beta2 Integrin/lipoprotein(a)	0.011	0.089	0.21	22	-0.21	42	64
TNF	-0.21	0.17	-10000	0	-0.48	119	119
RAP1B	0.02	0.005	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPA	0.04	0.11	0.22	87	-0.29	19	106
fibrinolysis	0.045	0.11	0.22	80	-0.27	18	98
HCK	0.005	0.07	-10000	0	-0.33	22	22
dendritic cell antigen processing and presentation	-0.066	0.14	0.21	2	-0.38	58	60
VTN	-0.033	0.14	0.32	7	-0.33	85	92
alphaM/beta2 Integrin/CYR61	-0.001	0.089	-10000	0	-0.26	39	39
LPA	0.018	0.025	0.32	2	-0.33	1	3
LRP1	0.018	0.031	-10000	0	-0.33	4	4
cell migration	0.023	0.077	0.24	2	-0.24	17	19
FN1	0.019	0.033	0.32	1	-0.33	4	5
alphaM/beta2 Integrin/Thy1	0.011	0.081	0.22	13	-0.28	20	33
MPO	0.012	0.056	0.32	1	-0.33	13	14
KNG1	0.039	0.077	0.32	35	-10000	0	35
RAP1/GDP	0.026	0.008	-10000	0	-10000	0	0
ROCK1	-0.073	0.15	0.24	5	-0.4	52	57
ELA2	0	0	-10000	0	-10000	0	0
PLG	0.023	0.045	0.32	11	-10000	0	11
CTGF	0.004	0.07	-10000	0	-0.33	22	22
alphaM/beta2 Integrin/Hck	0	0.093	-10000	0	-0.32	28	28
ITGAM	-0.008	0.073	-10000	0	-0.34	20	20
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.026	0.12	-10000	0	-0.23	102	102
HP	-0.041	0.16	0.32	23	-0.33	110	133
leukocyte adhesion	-0.19	0.13	-10000	0	-0.34	143	143
SELP	-0.049	0.14	-10000	0	-0.33	101	101

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.012	0.093	0.47	14	-10000	0	14
VDR	0.021	0.021	0.32	1	-0.33	1	2
FAM120B	0.019	0.006	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.087	0.11	-10000	0	-0.32	31	31
RXRs/LXRs/DNA/Oxysterols	-0.087	0.12	-10000	0	-0.48	22	22
MED1	0.021	0.004	-10000	0	-10000	0	0
mol:9cRA	-0.001	0.009	-10000	0	-0.093	1	1
RARs/THRs/DNA/Src-1	-0.009	0.066	-10000	0	-0.19	45	45
RXRs/NUR77	-0.096	0.13	-10000	0	-0.21	275	275
RXRs/PPAR	-0.11	0.13	-10000	0	-0.23	252	252
NCOR2	0.021	0.003	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.015	0.014	0.22	1	-0.22	1	2
RARs/VDR/DNA/Vit D3	0.045	0.023	0.21	1	-0.17	3	4
RARA	0.021	0.004	-10000	0	-10000	0	0
NCOA1	0.021	0.002	-10000	0	-10000	0	0
VDR/VDR/DNA	0.021	0.021	0.32	1	-0.32	1	2
RARs/RARs/DNA/9cRA	0.032	0.021	-10000	0	-0.17	2	2
RARG	0.021	0.003	-10000	0	-10000	0	0
RPS6KB1	0.03	0.11	0.62	16	-10000	0	16
RARs/THRs/DNA/SMRT	-0.01	0.067	-10000	0	-0.19	47	47
THRA	0.021	0.004	-10000	0	-10000	0	0
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.015	0.014	0.22	1	-0.22	1	2
RXRs/PPAR/9cRA/PGJ2/DNA	-0.066	0.11	-10000	0	-0.18	230	230
NR1H4	0.041	0.078	0.32	36	-10000	0	36
RXRs/LXRs/DNA	-0.056	0.12	-10000	0	-0.25	14	14
NR1H2	0.019	0.014	-10000	0	-10000	0	0
NR1H3	0.019	0.015	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.058	0.1	-10000	0	-0.17	232	232
NR4A1	-0.047	0.14	-10000	0	-0.33	100	100
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.071	0.096	0.17	1	-0.17	217	218
RXRG	-0.14	0.17	-10000	0	-0.33	238	238
RXR alpha/CCPG	0.026	0.016	-10000	0	-10000	0	0
RXRA	0.019	0.015	-10000	0	-10000	0	0
RXRB	0.019	0.015	-10000	0	-10000	0	0
THRB	-0.011	0.1	-10000	0	-0.33	47	47
PPARG	-0.023	0.12	-10000	0	-0.33	64	64
PPARD	0.021	0.004	-10000	0	-10000	0	0
TNF	-0.095	0.18	-10000	0	-0.86	19	19
mol:Oxysterols	0	0.009	-10000	0	-10000	0	0
cholesterol transport	-0.086	0.12	-10000	0	-0.48	22	22
PPARA	0.02	0.005	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.019	0.022	-10000	0	-0.33	2	2
RXRs/NUR77/BCL2	-0.12	0.13	-10000	0	-0.23	273	273
SREBF1	-0.075	0.12	-10000	0	-0.51	12	12
RXRs/RXRs/DNA/9cRA	-0.066	0.11	-10000	0	-0.18	230	230
ABCA1	-0.08	0.12	-10000	0	-0.55	15	15
RARs/THRs	0.037	0.069	-10000	0	-0.18	44	44
RXRs/FXR	-0.056	0.12	0.23	14	-0.18	218	232
BCL2	0.019	0.021	0.32	1	-0.33	1	2

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.3	0.55	0.74	4	-1.2	91	95
STAT6 (cleaved dimer)	-0.32	0.54	-10000	0	-1.2	98	98
IGHG1	-0.084	0.24	0.43	16	-0.65	15	31
IGHG3	-0.3	0.53	0.6	4	-1.1	102	106
AKT1	-0.14	0.32	0.52	2	-0.9	37	39
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.11	0.3	0.51	2	-0.92	35	37
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.14	0.32	0.49	5	-0.88	35	40
THY1	-0.3	0.56	0.71	4	-1.2	92	96
MYB	0.02	0.029	0.32	3	-0.33	1	4
HMGA1	0.045	0.082	0.32	41	-10000	0	41
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.16	0.36	0.55	9	-0.78	63	72
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.14	0.32	0.5	4	-0.89	35	39
SP1	0.026	0.024	-10000	0	-10000	0	0
INPP5D	0.019	0.027	-10000	0	-0.33	3	3
SOCS5	0.011	0.036	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.3	0.54	0.61	1	-1.2	94	95
SOCS1	-0.19	0.36	0.55	2	-0.76	84	86
SOCS3	-0.14	0.3	0.52	1	-0.83	30	31
FCER2	-0.23	0.49	0.72	9	-1.1	70	79
PARP14	0.023	0.012	-10000	0	-10000	0	0
CCL17	-0.35	0.62	0.78	5	-1.4	106	111
GRB2	0.02	0.004	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.1	0.27	0.46	7	-0.74	33	40
T cell proliferation	-0.31	0.55	0.63	1	-1.3	93	94
IL4R/JAK1	-0.31	0.55	-10000	0	-1.2	92	92
EGR2	-0.32	0.6	0.77	4	-1.3	94	98
JAK2	-0.006	0.064	0.18	5	-0.37	2	7
JAK3	0.02	0.016	-10000	0	-10000	0	0
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
JAK1	0.003	0.034	-10000	0	-10000	0	0
COL1A2	-0.064	0.22	0.48	3	-1.3	4	7
CCL26	-0.29	0.56	0.78	5	-1.3	85	90
IL4R	-0.32	0.59	0.77	7	-1.3	91	98
PTPN6	0.015	0.03	-10000	0	-10000	0	0
IL13RA2	-0.33	0.6	0.73	4	-1.3	103	107
IL13RA1	-0.006	0.064	0.18	6	-10000	0	6
IRF4	-0.057	0.26	0.54	2	-0.98	25	27
ARG1	-0.092	0.25	0.5	4	-0.7	33	37
CBL	-0.16	0.33	0.5	6	-0.74	59	65
GTF3A	0.063	0.059	-10000	0	-10000	0	0
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
IL13RA1/JAK2	0	0.088	0.23	15	-0.27	2	17
IRF4/BCL6	-0.061	0.23	-10000	0	-0.91	25	25
CD40LG	0.01	0.076	-10000	0	-0.33	23	23
MAPK14	-0.15	0.33	0.5	6	-0.81	46	52
mitosis	-0.13	0.3	0.49	3	-0.83	37	40
STAT6	-0.35	0.67	0.85	7	-1.4	102	109
SPI1	0.006	0.074	-10000	0	-0.33	24	24
RPS6KB1	-0.13	0.29	0.49	2	-0.8	36	38
STAT6 (dimer)	-0.35	0.67	0.88	6	-1.4	102	108
STAT6 (dimer)/PARP14	-0.33	0.6	0.67	4	-1.3	101	105
mast cell activation	0.005	0.017	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.17	0.36	0.49	4	-0.9	59	63
FRAP1	-0.14	0.32	0.52	2	-0.9	37	39
LTA	-0.3	0.55	0.72	5	-1.2	90	95
FES	0.02	0.016	-10000	0	-0.33	1	1
T-helper 1 cell differentiation	0.34	0.64	1.4	102	-0.87	6	108
CCL11	-0.32	0.55	-10000	0	-1.2	101	101
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.14	0.33	0.49	4	-0.96	36	40
IL2RG	0.017	0.036	-10000	0	-0.3	5	5
IL10	-0.3	0.56	0.74	6	-1.3	87	93
IRS1	0.02	0.016	-10000	0	-0.33	1	1
IRS2	0.019	0.016	-10000	0	-0.33	1	1
IL4	-0.072	0.27	0.52	6	-1.1	23	29
IL5	-0.31	0.55	0.69	3	-1.2	90	93
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.25	0.49	0.67	11	-1	98	109
COL1A1	-0.013	0.29	0.58	16	-0.88	15	31
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.32	0.56	-10000	0	-1.3	90	90
IL2R gamma/JAK3	0.028	0.029	-10000	0	-0.19	5	5
TFF3	-0.3	0.59	0.72	8	-1.3	99	107
ALOX15	-0.62	0.72	0.7	2	-1.3	236	238
MYBL1	0.023	0.033	0.32	6	-10000	0	6
T-helper 2 cell differentiation	-0.24	0.47	0.63	6	-0.98	96	102
SHC1	0.018	0.016	0.32	1	-10000	0	1
CEBPB	0.021	0.01	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.13	0.31	0.48	4	-0.83	33	37
mol:PI-3-4-5-P3	-0.14	0.32	0.52	2	-0.9	37	39
PI3K	-0.15	0.34	0.52	2	-0.98	37	39
DOK2	-0.004	0.085	-10000	0	-0.33	33	33
ETS1	0.011	0.039	-10000	0	-0.22	2	2
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.091	0.24	0.44	7	-0.66	29	36
ITGB3	-0.3	0.56	0.7	3	-1.3	88	91
PIGR	-0.43	0.69	0.74	6	-1.4	149	155
IGHE	0.008	0.073	0.2	21	-0.2	8	29
MAPKKK cascade	-0.089	0.24	0.44	7	-0.64	29	36
BCL6	0.017	0.015	-10000	0	-10000	0	0
OPRM1	-0.31	0.55	0.7	2	-1.2	89	91
RETNLB	-0.3	0.55	0.69	3	-1.2	91	94
SELP	-0.41	0.68	0.72	5	-1.4	135	140
AICDA	-0.32	0.56	0.7	2	-1.2	98	100

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.015	0.043	-10000	0	-0.33	8	8
EPHB2	0.054	0.094	0.32	55	-10000	0	55
EFNB1	-0.011	0.03	0.18	8	-0.23	2	10
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.063	0.081	0.28	18	-0.23	6	24
Ephrin B2/EPHB1-2	0.067	0.083	0.23	93	-0.16	10	103
neuron projection morphogenesis	0.043	0.063	0.22	17	-0.22	6	23
Ephrin B1/EPHB1-2/Tiam1	0.07	0.089	0.24	89	-0.23	7	96
DNM1	0.025	0.036	0.33	7	-10000	0	7
cell-cell signaling	0	0.004	-10000	0	-10000	0	0
MAP2K4	-0.061	0.16	-10000	0	-0.5	59	59
YES1	-0.074	0.24	-10000	0	-0.72	60	60
Ephrin B1/EPHB1-2/NCK2	0.077	0.085	0.24	96	-0.2	5	101
PI3K	-0.03	0.17	-10000	0	-0.49	61	61
mol:GDP	0.067	0.087	0.23	89	-0.23	7	96
ITGA2B	-0.008	0.1	0.32	5	-0.33	47	52
endothelial cell proliferation	0.022	0.028	-10000	0	-0.19	8	8
FYN	-0.078	0.24	-10000	0	-0.72	60	60
MAP3K7	-0.06	0.17	-10000	0	-0.52	59	59
FGR	-0.079	0.24	-10000	0	-0.72	60	60
TIAM1	0.015	0.043	-10000	0	-0.33	8	8
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
RGS3	0.02	0.004	-10000	0	-10000	0	0
cell adhesion	-0.05	0.17	0.24	1	-0.49	58	59
LYN	-0.071	0.23	-10000	0	-0.71	59	59
Ephrin B1/EPHB1-2/Src Family Kinases	-0.069	0.21	-10000	0	-0.64	61	61
Ephrin B1/EPHB1-2	-0.06	0.18	-10000	0	-0.56	59	59
SRC	-0.071	0.23	-10000	0	-0.7	61	61
ITGB3	0.031	0.072	0.32	23	-0.33	5	28
EPHB1	0.052	0.099	0.32	55	-0.33	3	58
EPHB4	0.02	0.005	-10000	0	-10000	0	0
RAC1	0.019	0.007	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.022	0.028	-10000	0	-0.19	8	8
alphaIIb/beta3 Integrin	0.015	0.095	0.23	28	-0.23	51	79
BLK	-0.068	0.24	-10000	0	-0.71	60	60
HCK	-0.078	0.24	-10000	0	-0.72	61	61
regulation of stress fiber formation	-0.074	0.083	0.2	5	-0.23	96	101
MAPK8	-0.06	0.15	0.23	1	-0.47	60	61
Ephrin B1/EPHB1-2/RGS3	0.074	0.083	0.23	92	-0.2	5	97
endothelial cell migration	-0.045	0.14	0.19	16	-0.43	55	71
NCK2	0.021	0.002	-10000	0	-10000	0	0
PTPN13	-0.024	0.14	-10000	0	-0.44	51	51
regulation of focal adhesion formation	-0.074	0.083	0.2	5	-0.23	96	101
chemotaxis	-0.071	0.081	0.2	5	-0.23	92	97
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
Rac1/GTP	0.054	0.073	0.25	18	-0.23	6	24
angiogenesis	-0.059	0.18	-10000	0	-0.56	59	59
LCK	-0.071	0.23	-10000	0	-0.7	61	61

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.021	0.003	-10000	0	-10000	0	0
GNAT1/GTP	0.017	0.028	0.22	10	-10000	0	10
Metarhodopsin II/Arrestin	0.025	0.009	0.21	1	-10000	0	1
PDE6G/GNAT1/GTP	0.028	0.034	0.23	10	-0.17	3	13
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	0.024	0.043	0.32	10	-10000	0	10
GRK1	0.037	0.074	0.32	32	-10000	0	32
CNG Channel	0.043	0.085	0.26	17	-0.17	32	49
mol:Na +	0.081	0.082	0.28	33	-0.17	3	36
mol:ADP	0.037	0.074	0.32	32	-10000	0	32
RGS9-1/Gbeta5/R9AP	-0.058	0.13	-10000	0	-0.21	193	193
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	0.1	0.096	0.33	34	-0.17	3	37
CNGB1	0.071	0.12	0.32	87	-0.33	1	88
RDH5	0.025	0.035	0.32	7	-10000	0	7
SAG	0.019	0.014	0.32	1	-10000	0	1
mol:Ca2+	0.015	0.089	0.3	31	-10000	0	31
Na + (4 Units)	0.024	0.081	0.15	88	-0.16	3	91
RGS9	-0.081	0.16	-10000	0	-0.33	149	149
GNB1/GNGT1	0.063	0.079	0.23	89	-10000	0	89
GNAT1/GDP	-0.042	0.12	0.21	5	-0.18	187	192
GUCY2D	0.021	0.043	0.32	6	-0.33	3	9
GNGT1	0.077	0.12	0.32	98	-10000	0	98
GUCY2F	0.02	0.019	0.32	2	-10000	0	2
GNB5	0.021	0.004	-10000	0	-10000	0	0
mol:GMP (4 units)	-0.029	0.049	0.18	2	-0.18	40	42
mol:11-cis-retinal	0.025	0.035	0.32	7	-10000	0	7
mol:cGMP	0.061	0.075	0.22	82	-0.16	5	87
GNB1	0.021	0.004	-10000	0	-10000	0	0
Rhodopsin	0.032	0.024	0.23	7	-10000	0	7
SLC24A1	0.021	0.003	-10000	0	-10000	0	0
CNGA1	0.057	0.099	0.32	62	-10000	0	62
Metarhodopsin II	0.033	0.042	0.2	31	-10000	0	31
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.073	0.078	0.23	86	-0.17	5	91
RGS9BP	-0.03	0.12	-10000	0	-0.33	73	73
Metarhodopsin II/Transducin	0.026	0.039	0.16	8	-10000	0	8
GCAP Family/Ca ++	0.065	0.07	0.22	85	-0.15	2	87
PDE6A/B	0.007	0.073	0.23	1	-0.23	44	45
mol:Pi	-0.058	0.13	-10000	0	-0.21	193	193
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	0.066	0.072	0.22	91	-10000	0	91
PDE6B	0.016	0.04	-10000	0	-0.33	7	7
PDE6A	-0.006	0.093	0.32	1	-0.33	39	40
PDE6G	0.02	0.033	0.32	2	-0.33	3	5
RHO	0.019	0.003	-10000	0	-10000	0	0
PDE6	-0.048	0.13	-10000	0	-0.21	181	181
GUCA1A	0.071	0.11	0.32	86	-10000	0	86
GC2/GCAP Family	0.076	0.072	0.23	86	-0.15	2	88
GUCA1C	0.018	0.014	0.32	1	-10000	0	1
GUCA1B	0.021	0.032	0.32	3	-0.33	2	5

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.021	0.004	-10000	0	-10000	0	0
CCL5	0.017	0.034	-10000	0	-0.33	5	5
SDCBP	0.019	0.006	-10000	0	-10000	0	0
FGFR/FGF2/Syndecan-1	0.08	0.081	0.23	48	-0.26	2	50
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
Syndecan-1/Laminin-5	0.072	0.089	0.22	36	-0.32	5	41
Syndecan-1/Syntenin	0.071	0.091	0.23	36	-0.32	6	42
MAPK3	0.056	0.088	0.21	40	-0.28	6	46
HGF/MET	0.013	0.078	0.23	10	-0.23	40	50
TGFB1/TGF beta receptor Type II	0.02	0.004	-10000	0	-10000	0	0
BSG	0.02	0.006	-10000	0	-10000	0	0
keratinocyte migration	0.071	0.088	0.22	36	-0.31	5	41
Syndecan-1/RANTES	0.076	0.093	0.23	40	-0.29	7	47
Syndecan-1/CD147	0.082	0.092	0.27	12	-0.29	6	18
Syndecan-1/Syntenin/PIP2	0.066	0.086	0.21	35	-0.31	6	41
LAMA5	0.018	0.027	-10000	0	-0.33	3	3
positive regulation of cell-cell adhesion	0.064	0.084	0.21	35	-0.3	6	41
MMP7	0.063	0.13	0.32	85	-0.33	11	96
HGF	0.006	0.079	0.32	4	-0.33	24	28
Syndecan-1/CASK	0.059	0.086	0.15	147	-0.27	9	156
Syndecan-1/HGF/MET	0.067	0.11	0.24	42	-0.33	9	51
regulation of cell adhesion	0.048	0.081	0.19	41	-0.27	6	47
HPSE	0.022	0.019	0.32	2	-10000	0	2
positive regulation of cell migration	0.08	0.081	0.23	48	-0.26	2	50
SDC1	0.079	0.08	0.22	47	-0.26	2	49
Syndecan-1/Collagen	0.08	0.081	0.23	48	-0.26	2	50
PPIB	0.021	0.014	0.32	1	-10000	0	1
MET	0.011	0.072	0.32	6	-0.33	18	24
PRKACA	0.02	0.005	-10000	0	-10000	0	0
MMP9	0.084	0.12	0.32	109	-10000	0	109
MAPK1	0.057	0.085	0.2	38	-0.27	6	44
homophilic cell adhesion	0.077	0.09	0.23	48	-0.24	3	51
MMP1	0.21	0.15	0.32	324	-0.33	2	326

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.029	0.018	-10000	0	-0.23	2	2
Necdin/E2F1	0.029	0.031	0.23	5	-0.22	4	9
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.049	0.07	-10000	0	-0.17	28	28
NGF (dimer)/p75(NTR)/BEX1	-0.01	0.13	0.24	35	-0.2	133	168
NT-4/5 (dimer)/p75(NTR)	0.016	0.072	0.27	7	-0.23	33	40
IKBKB	0.018	0.007	-10000	0	-10000	0	0
AKT1	-0.019	0.053	0.18	19	-0.17	20	39
IKBKG	0.02	0.004	-10000	0	-10000	0	0
BDNF	-0.15	0.17	-10000	0	-0.33	258	258
MGDIs/NGR/p75(NTR)/LINGO1	0.056	0.071	0.23	60	-0.18	10	70
FURIN	0.029	0.05	0.32	14	-10000	0	14
proBDNF (dimer)/p75(NTR)/Sortilin	-0.077	0.12	0.22	5	-0.2	253	258
LINGO1	0.059	0.1	0.32	64	-10000	0	64
Sortilin/TRAF6/NRIF	-0.028	0.019	-10000	0	-10000	0	0
proBDNF (dimer)	-0.15	0.17	-10000	0	-0.32	258	258
NTRK1	0.01	0.056	0.32	1	-0.33	13	14
RTN4R	0.019	0.016	-10000	0	-0.33	1	1
neuron apoptosis	-0.099	0.14	0.34	2	-0.4	40	42
IRAK1	0.02	0.004	-10000	0	-10000	0	0
SHC1	-0.014	0.041	0.1	26	-0.2	14	40
ARHGDIA	0.02	0.004	-10000	0	-10000	0	0
RhoA/GTP	0.015	0.003	-10000	0	-10000	0	0
Gamma Secretase	0.046	0.031	-10000	0	-0.18	1	1
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.048	0.066	0.23	27	-0.18	24	51
MAGEH1	0.021	0.003	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	0.044	0.07	0.23	26	-0.19	26	52
Mammalian IAPs/DIABLO	0.051	0.028	0.23	5	-0.18	2	7
proNGF (dimer)	0.025	0.085	0.32	23	-0.32	13	36
MAGED1	0.021	0.014	0.32	1	-10000	0	1
APP	0.02	0.005	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.003	0.077	0.32	1	-0.32	26	27
ZNF274	0.02	0.004	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	0.02	0.045	0.19	1	-0.16	22	23
NGF	0.025	0.085	0.32	23	-0.33	13	36
cell cycle arrest	0.002	0.071	0.26	14	-10000	0	14
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.006	0.057	0.18	6	-0.2	20	26
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.028	0.066	0.25	7	-0.2	33	40
NCSTN	0.019	0.007	-10000	0	-10000	0	0
mol:GTP	0.039	0.065	0.22	28	-0.19	21	49
PSENEN	0.02	0.005	-10000	0	-10000	0	0
mol:ceramide	-0.016	0.05	0.2	10	-0.18	18	28
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.004	0.051	-10000	0	-0.28	3	3
p75(NTR)/beta APP	0.027	0.043	0.23	7	-0.23	9	16
BEX1	-0.052	0.16	0.32	19	-0.33	124	143
mol:GDP	-0.014	0.046	0.21	1	-0.19	22	23
NGF (dimer)	0.072	0.096	0.23	108	-0.18	18	126
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.065	0.069	0.23	59	-0.17	10	69
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
RAC1/GTP	0.03	0.054	0.2	22	-0.16	21	43
MYD88	0.021	0.004	-10000	0	-10000	0	0
CHUK	0.021	0.003	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	0.04	0.065	0.22	28	-0.19	21	49
RHOB	0.02	0.015	-10000	0	-0.33	1	1
RHOA	0.02	0.004	-10000	0	-10000	0	0
MAGE-G1/E2F1	0.03	0.02	0.23	4	-10000	0	4
NT3 (dimer)	0.006	0.074	0.32	2	-0.32	23	25
TP53	-0.085	0.088	0.26	6	-0.3	6	12
PRDM4	-0.018	0.053	0.2	12	-0.18	21	33
BDNF (dimer)	-0.011	0.17	0.26	105	-0.18	136	241
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
SORT1	0.019	0.022	-10000	0	-0.33	2	2
activation of caspase activity	0.043	0.066	-10000	0	-0.17	28	28
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.048	0.066	0.23	27	-0.18	24	51
RHOC	0.02	0.004	-10000	0	-10000	0	0
XIAP	0.021	0.003	-10000	0	-10000	0	0
MAPK10	-0.077	0.12	0.3	11	-0.33	47	58
DIABLO	0.021	0.003	-10000	0	-10000	0	0
SMPD2	-0.016	0.05	0.2	10	-0.18	18	28
APH1B	0.019	0.022	-10000	0	-0.33	2	2
APH1A	0.017	0.008	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	0.039	0.067	0.22	27	-0.19	24	51
PSEN1	0.021	0.004	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.03	0.007	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	0.017	0.072	0.29	7	-0.23	31	38
MAPK8	-0.062	0.1	0.32	9	-0.29	27	36
MAPK9	-0.061	0.1	0.32	9	-0.29	25	34
APAF1	0.021	0.003	-10000	0	-10000	0	0
NTF3	0.006	0.075	0.32	2	-0.33	23	25
NTF4	0.003	0.077	0.32	1	-0.33	26	27
NDN	0.017	0.034	-10000	0	-0.33	5	5
RAC1/GDP	0.014	0.005	-10000	0	-10000	0	0
RhoA-B-C/GDP	0.047	0.057	-10000	0	-0.16	21	21
p75 CTF/Sortilin/TRAF6/NRIF	0.049	0.022	-10000	0	-0.18	2	2
RhoA-B-C/GTP	0.039	0.064	0.22	28	-0.19	21	49
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.058	0.12	-10000	0	-0.18	234	234
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.064	0.12	0.23	5	-0.18	250	255
PRKACB	0.021	0.014	0.32	1	-10000	0	1
proBDNF (dimer)/p75 ECD	-0.1	0.13	-10000	0	-0.23	255	255
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.022	0.037	0.32	5	-0.33	2	7
BIRC2	0.02	0.005	-10000	0	-10000	0	0
neuron projection morphogenesis	0.007	0.072	0.23	14	-0.2	14	28
BAD	-0.072	0.11	0.33	11	-0.32	31	42
RIPK2	0.019	0.007	-10000	0	-10000	0	0
NGFR	0.019	0.058	0.32	7	-0.33	9	16
CYCS	-0.02	0.052	0.21	11	-10000	0	11
ADAM17	0.021	0.003	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.044	0.064	0.23	24	-0.18	21	45
BCL2L11	-0.072	0.11	0.34	10	-0.32	31	41
BDNF (dimer)/p75(NTR)	-0.098	0.14	0.23	5	-0.23	254	259
PI3K	0.046	0.065	0.23	26	-0.18	22	48
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.047	0.066	0.23	27	-0.18	23	50
NDNL2	0.02	0.005	-10000	0	-10000	0	0
YWHAE	0.019	0.006	-10000	0	-10000	0	0
PRKCI	0.02	0.005	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	0.029	0.072	0.23	28	-0.23	22	50
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.048	0.066	0.23	27	-0.18	23	50
TRAF6	0.021	0.003	-10000	0	-10000	0	0
RAC1	0.019	0.007	-10000	0	-10000	0	0
PRKCZ	0.019	0.027	-10000	0	-0.33	3	3
PLG	0.023	0.045	0.32	11	-10000	0	11
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.098	0.097	-10000	0	-0.19	245	245
SQSTM1	0.02	0.005	-10000	0	-10000	0	0
NGFRAP1	0.018	0.034	-10000	0	-0.33	5	5
CASP3	-0.068	0.11	0.33	10	-0.3	33	43
E2F1	0.023	0.03	0.32	5	-10000	0	5
CASP9	0.021	0.004	-10000	0	-10000	0	0
IKK complex	0.03	0.069	0.23	3	-0.27	8	11
NGF (dimer)/TRKA	0.023	0.067	0.23	19	-0.22	22	41
MMP7	0.063	0.13	0.32	85	-0.33	11	96
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.054	0.065	-10000	0	-0.18	22	22
MMP3	0.13	0.15	0.32	186	-10000	0	186
APAF-1/Caspase 9	-0.039	0.035	-10000	0	-10000	0	0

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.017	0.027	-10000	0	-0.33	3	3
GNB1/GNG2	-0.051	0.071	-10000	0	-0.19	102	102
AKT1	-0.04	0.1	0.29	1	-0.27	26	27
EGF	0.071	0.12	0.32	91	-0.33	5	96
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	-0.03	0.06	-10000	0	-0.23	17	17
mol:Ca2+	-0.064	0.14	-10000	0	-0.31	99	99
LYN	-0.021	0.041	-10000	0	-0.21	3	3
RhoA/GTP	-0.026	0.057	-10000	0	-0.13	81	81
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.074	0.15	-10000	0	-0.34	104	104
GNG2	0.019	0.022	-10000	0	-0.33	2	2
ARRB2	0.02	0.006	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.032	0.15	-10000	0	-0.6	29	29
G beta5/gamma2	-0.064	0.093	-10000	0	-0.24	99	99
PRKCH	-0.074	0.16	0.31	1	-0.35	103	104
DNM1	0.025	0.035	0.32	7	-10000	0	7
TXA2/TP beta/beta Arrestin3	0.008	0.045	-10000	0	-0.53	3	3
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	0.013	0.05	-10000	0	-0.33	11	11
G12 family/GTP	-0.063	0.13	-10000	0	-0.3	99	99
ADRBK1	0.021	0.004	-10000	0	-10000	0	0
ADRBK2	0.02	0.005	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0.026	0.008	-10000	0	-10000	0	0
mol:GDP	0.044	0.11	0.37	27	-10000	0	27
mol:NADP	0.022	0.047	0.32	7	-0.33	4	11
RAB11A	0.021	0.003	-10000	0	-10000	0	0
PRKG1	-0.022	0.11	-10000	0	-0.33	63	63
mol:IP3	-0.082	0.17	-10000	0	-0.38	103	103
cell morphogenesis	0.026	0.008	-10000	0	-10000	0	0
PLCB2	-0.12	0.23	-10000	0	-0.52	105	105
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	0.007	0.074	0.26	4	-0.21	1	5
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.026	0.052	-10000	0	-0.23	11	11
RHOA	0.02	0.004	-10000	0	-10000	0	0
PTGIR	0.016	0.038	-10000	0	-0.33	6	6
PRKCB1	-0.079	0.17	-10000	0	-0.38	104	104
GNAQ	0.02	0.016	-10000	0	-0.33	1	1
mol:L-citrulline	0.022	0.047	0.32	7	-0.33	4	11
TXA2/TXA2-R family	-0.11	0.22	-10000	0	-0.52	105	105
LCK	-0.022	0.047	-10000	0	-0.21	6	6
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.01	0.048	-10000	0	-0.25	5	5
TXA2-R family/G12 family/GDP/G beta/gamma	0.009	0.062	-10000	0	-0.42	9	9
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.011	0.045	-10000	0	-0.23	6	6
MAPK14	-0.047	0.1	0.27	7	-0.23	91	98
TGM2/GTP	-0.091	0.18	-10000	0	-0.42	98	98
MAPK11	-0.051	0.1	-10000	0	-0.23	96	96
ARHGEF1	-0.043	0.074	-10000	0	-0.18	87	87
GNAI2	0.02	0.004	-10000	0	-10000	0	0
JNK cascade	-0.081	0.17	-10000	0	-0.38	105	105
RAB11/GDP	0.021	0.005	-10000	0	-10000	0	0
ICAM1	-0.059	0.12	-10000	0	-0.28	101	101
cAMP biosynthetic process	-0.077	0.16	-10000	0	-0.35	99	99
Gq family/GTP/EBP50	0	0.044	0.23	1	-0.19	20	21
actin cytoskeleton reorganization	0.026	0.008	-10000	0	-10000	0	0
SRC	-0.021	0.043	-10000	0	-0.2	4	4
GNB5	0.02	0.004	-10000	0	-10000	0	0
GNB1	0.021	0.004	-10000	0	-10000	0	0
EGF/EGFR	-0.008	0.08	0.19	12	-0.24	19	31
VCAM1	-0.06	0.13	-10000	0	-0.29	102	102
TP beta/Gq family/GDP/G beta5/gamma2	-0.032	0.15	-10000	0	-0.6	29	29
platelet activation	-0.063	0.14	0.3	5	-0.3	95	100
PGI2/IP	0.012	0.026	-10000	0	-0.22	6	6
PRKACA	0.002	0.041	-10000	0	-0.22	15	15
Gq family/GDP/G beta5/gamma2	-0.018	0.12	-10000	0	-0.52	21	21
TXA2/TP beta/beta Arrestin2	-0.004	0.059	-10000	0	-0.36	8	8
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.013	0.033	-10000	0	-0.2	13	13
mol:DAG	-0.09	0.19	-10000	0	-0.42	106	106
EGFR	0.014	0.045	0.32	1	-0.33	8	9
TXA2/TP alpha	-0.11	0.21	-10000	0	-0.48	103	103
Gq family/GTP	-0.014	0.066	0.22	1	-0.22	42	43
YES1	-0.02	0.043	-10000	0	-0.2	4	4
GNAI2/GTP	-0.005	0.042	-10000	0	-0.2	9	9
PGD2/DP	0.01	0.035	-10000	0	-0.22	11	11
SLC9A3R1	0.021	0.014	0.32	1	-10000	0	1
FYN	-0.02	0.042	-10000	0	-0.2	4	4
mol:NO	0.022	0.047	0.32	7	-0.33	4	11
GNA15	0.02	0.006	-10000	0	-10000	0	0
PGK/cGMP	0.003	0.076	0.21	7	-0.19	61	68
RhoA/GDP	0.02	0.006	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0.02	0.051	-10000	0	-0.24	7	7
NOS3	0.022	0.047	0.32	7	-0.33	4	11
RAC1	0.019	0.007	-10000	0	-10000	0	0
PRKCA	-0.074	0.16	0.31	1	-0.36	101	102
PRKCB	-0.078	0.16	-10000	0	-0.36	104	104
PRKCE	-0.075	0.16	-10000	0	-0.36	102	102
PRKCD	-0.081	0.16	-10000	0	-0.38	103	103
PRKCG	-0.079	0.17	-10000	0	-0.38	103	103
muscle contraction	-0.11	0.21	-10000	0	-0.48	105	105
PRKCZ	-0.074	0.15	-10000	0	-0.34	104	104
ARR3	0.02	0.023	0.32	3	-10000	0	3
TXA2/TP beta	0.007	0.048	-10000	0	-0.21	8	8
PRKCQ	-0.086	0.16	-10000	0	-0.38	107	107
MAPKKK cascade	-0.1	0.2	-10000	0	-0.46	104	104
SELE	-0.074	0.15	-10000	0	-0.36	102	102
TP beta/GNAI2/GDP/G beta/gamma	0.021	0.05	-10000	0	-0.23	6	6
ROCK1	0.02	0.005	-10000	0	-10000	0	0
GNA14	0.013	0.05	-10000	0	-0.33	11	11
chemotaxis	-0.12	0.25	-10000	0	-0.59	103	103
GNA12	0.019	0.007	-10000	0	-10000	0	0
GNA13	0.02	0.004	-10000	0	-10000	0	0
GNA11	0.019	0.016	-10000	0	-0.33	1	1
Rac1/GTP	0.013	0.005	-10000	0	-10000	0	0

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	0.069	0.11	0.34	74	-0.22	2	76
NFATC2	0.003	0.14	-10000	0	-0.5	16	16
NFATC3	-0.007	0.084	-10000	0	-0.26	35	35
CD40LG	-0.092	0.29	0.41	1	-0.77	66	67
ITCH	-0.024	0.077	-10000	0	-0.2	83	83
CBLB	-0.027	0.08	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.032	0.26	0.48	15	-0.73	35	50
JUNB	0.018	0.027	-10000	0	-0.33	3	3
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.026	0.099	-10000	0	-0.23	94	94
T cell anergy	-0.056	0.14	0.28	4	-0.34	86	90
TLE4	-0.01	0.1	-10000	0	-0.44	14	14
Jun/NFAT1-c-4/p21SNFT	-0.04	0.29	0.51	1	-0.78	58	59
AP-1/NFAT1-c-4	-0.053	0.35	0.6	3	-0.86	63	66
IKZF1	-0.005	0.087	-10000	0	-0.37	13	13
T-helper 2 cell differentiation	-0.032	0.19	-10000	0	-0.71	23	23
AP-1/NFAT1	0.014	0.12	0.33	3	-0.35	17	20
CALM1	-0.009	0.067	-10000	0	-0.18	1	1
EGR2	-0.096	0.33	-10000	0	-1	45	45
EGR3	-0.13	0.41	-10000	0	-1.2	62	62
NFAT1/FOXP3	0.054	0.14	0.42	21	-0.34	12	33
EGR1	0.003	0.074	-10000	0	-0.33	24	24
JUN	0.012	0.037	-10000	0	-0.33	3	3
EGR4	0.05	0.092	0.32	52	-10000	0	52
mol:Ca2+	-0.024	0.054	-10000	0	-0.14	96	96
GBP3	-0.017	0.12	-10000	0	-0.52	22	22
FOSL1	0.028	0.059	0.32	16	-0.33	3	19
NFAT1-c-4/MAF/IRF4	-0.038	0.28	-10000	0	-0.75	61	61
DGKA	-0.006	0.091	0.5	1	-0.36	13	14
CREM	0.02	0.004	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.075	0.3	-10000	0	-0.81	64	64
CTLA4	0.015	0.099	0.36	10	-0.3	7	17
NFAT1-c-4 (dimer)/EGR1	-0.061	0.3	0.46	1	-0.81	64	65
NFAT1-c-4 (dimer)/EGR4	-0.036	0.3	0.46	2	-0.79	62	64
FOS	-0.004	0.081	-10000	0	-0.33	27	27
IFNG	-0.04	0.22	0.38	1	-0.84	23	24
T cell activation	-0.04	0.17	-10000	0	-0.64	17	17
MAF	0.02	0.016	-10000	0	-0.33	1	1
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.071	0.24	0.67	63	-10000	0	63
TNF	-0.081	0.28	0.48	1	-0.76	63	64
FASLG	-0.16	0.45	-10000	0	-1.2	68	68
TBX21	0.014	0.076	0.32	2	-0.32	20	22
BATF3	0.019	0.006	-10000	0	-10000	0	0
PRKCQ	-0.022	0.11	-10000	0	-0.33	63	63
PTPN1	-0.008	0.092	0.34	1	-0.38	10	11
NFAT1-c-4/ICER1	-0.052	0.29	-10000	0	-0.77	63	63
GATA3	0.02	0.021	0.32	1	-0.33	1	2
T-helper 1 cell differentiation	-0.039	0.22	0.38	1	-0.82	23	24
IL2RA	-0.021	0.26	0.48	23	-0.7	39	62
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.008	0.089	-10000	0	-0.4	7	7
E2F1	0.025	0.031	0.32	5	-10000	0	5
PPARG	-0.023	0.12	-10000	0	-0.33	64	64
SLC3A2	-0.007	0.088	-10000	0	-0.36	13	13
IRF4	0.026	0.055	0.32	13	-0.33	3	16
PTGS2	-0.094	0.29	0.46	2	-0.78	62	64
CSF2	-0.094	0.3	0.46	4	-0.78	65	69
JunB/Fra1/NFAT1-c-4	-0.039	0.29	0.49	2	-0.75	63	65
IL4	-0.034	0.2	-10000	0	-0.75	23	23
IL5	-0.089	0.28	0.41	1	-0.76	63	64
IL2	-0.04	0.17	-10000	0	-0.67	16	16
IL3	-0.029	0.14	-10000	0	-0.82	11	11
RNF128	-0.071	0.17	-10000	0	-0.43	94	94
NFATC1	-0.071	0.24	-10000	0	-0.67	63	63
CDK4	0.051	0.16	0.59	20	-10000	0	20
PTPRK	-0.005	0.085	-10000	0	-0.38	10	10
IL8	-0.082	0.29	0.44	8	-0.76	64	72
POU2F1	0.019	0.006	-10000	0	-10000	0	0

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.021	0.015	-10000	0	-0.17	1	1
ARNO/beta Arrestin1-2	-0.052	0.17	-10000	0	-0.82	19	19
EGFR	0.014	0.045	0.32	1	-0.33	8	9
EPHA2	0.014	0.048	-10000	0	-0.33	10	10
USP6	0.02	0.006	-10000	0	-10000	0	0
IQSEC1	0.02	0.016	-10000	0	-0.33	1	1
EGFR/EGFR/EGF/EGF	0.051	0.087	0.24	75	-0.23	12	87
ARRB2	0.017	0.037	0.14	42	-10000	0	42
mol:GTP	0.005	0.039	0.13	12	-0.14	9	21
ARRB1	0.017	0.034	-10000	0	-0.33	5	5
FBXO8	0.021	0.004	-10000	0	-10000	0	0
TSHR	0.052	0.093	0.32	54	-10000	0	54
EGF	0.071	0.12	0.32	91	-0.33	5	96
somatostatin receptor activity	0	0	0.001	13	-0.001	76	89
ARAP2	0.011	0.057	-10000	0	-0.33	14	14
mol:GDP	-0.065	0.14	0.17	8	-0.28	111	119
mol:PI-3-4-5-P3	0	0	0.001	11	-0.001	37	48
ITGA2B	-0.008	0.1	0.32	5	-0.33	47	52
ARF6	0.02	0.004	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.04	0.034	-10000	0	-0.18	7	7
ADAP1	0.018	0.017	-10000	0	-0.33	1	1
KIF13B	0.018	0.008	-10000	0	-10000	0	0
HGF/MET	0.013	0.078	0.23	10	-0.23	40	50
PXN	0.021	0.003	-10000	0	-10000	0	0
ARF6/GTP	-0.047	0.12	0.23	12	-0.24	80	92
EGFR/EGFR/EGF/EGF/ARFGEP100	0.055	0.077	0.23	67	-0.2	11	78
ADRB2	-0.11	0.17	-10000	0	-0.33	187	187
receptor agonist activity	0	0	0	4	0	81	85
actin filament binding	0	0	0.001	9	0	87	96
SRC	0.02	0.004	-10000	0	-10000	0	0
ITGB3	0.031	0.072	0.32	23	-0.33	5	28
GNAQ	0.02	0.016	-10000	0	-0.33	1	1
EFA6/PI-4-5-P2	0	0	0.001	16	-0.001	41	57
ARF6/GDP	-0.036	0.14	0.29	2	-0.39	51	53
ARF6/GDP/GULP/ACAP1	-0.047	0.14	-10000	0	-0.31	71	71
alphaIIb/beta3 Integrin/paxillin/GIT1	0.037	0.084	0.23	26	-0.18	50	76
ACAP1	0.019	0.016	-10000	0	-0.33	1	1
ACAP2	0.02	0.005	-10000	0	-10000	0	0
LHCGR/beta Arrestin2	0.032	0.071	0.25	44	-10000	0	44
EFNA1	0.017	0.017	-10000	0	-0.33	1	1
HGF	0.006	0.079	0.32	4	-0.33	24	28
CYTH3	-0.007	0.015	0.21	2	-10000	0	2
CYTH2	-0.023	0.19	-10000	0	-0.99	19	19
NCK1	0.021	0.003	-10000	0	-10000	0	0
fibronectin binding	0	0	0.001	12	0	51	63
endosomal lumen acidification	0	0	0	35	0	31	66
microtubule-based process	0	0	-10000	0	0	1	1
GULP1	0.018	0.031	-10000	0	-0.33	4	4
GNAQ/ARNO	-0.009	0.18	-10000	0	-0.92	19	19
mol:Phosphatidic acid	0	0	0	3	-10000	0	3
PIP3-E	0	0	0	7	0	12	19
MET	0.011	0.072	0.32	6	-0.33	18	24
GNA14	0.013	0.05	-10000	0	-0.33	11	11
GNA15	0.02	0.006	-10000	0	-10000	0	0
GIT1	0.021	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	0.001	10	-0.001	56	66
GNA11	0.019	0.016	-10000	0	-0.33	1	1
LHCGR	0.044	0.086	0.32	44	-10000	0	44
AGTR1	-0.088	0.16	0.32	1	-0.33	161	162
desensitization of G-protein coupled receptor protein signaling pathway	0.032	0.071	0.25	44	-10000	0	44
IPCEF1/ARNO	0.017	0.18	-10000	0	-0.84	19	19
alphaIIb/beta3 Integrin	0.015	0.095	0.23	28	-0.23	51	79

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	0.012	0.04	-10000	0	-0.3	7	7
CDKN2C	0.001	0.031	0.33	1	-10000	0	1
CDKN2A	0.098	0.14	0.33	135	-10000	0	135
CCND2	-0.021	0.048	0.15	6	-0.2	11	17
RB1	0.021	0.053	0.26	8	-0.17	5	13
CDK4	-0.023	0.052	0.17	6	-0.26	6	12
CDK6	-0.023	0.052	0.17	5	-0.26	7	12
G1/S progression	0.006	0.093	0.18	84	-0.28	9	93

IL23-mediated signaling events

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
CCL2	-0.12	0.45	0.67	2	-1.2	53	55
IL23A	-0.1	0.47	0.75	4	-1.2	50	54
NF kappa B1 p50/RelA/I kappa B alpha	-0.1	0.45	0.64	3	-1.2	49	52
positive regulation of T cell mediated cytotoxicity	-0.13	0.52	0.74	3	-1.4	53	56
ITGA3	-0.11	0.45	0.69	2	-1.1	53	55
IL17F	-0.074	0.31	0.52	8	-0.72	53	61
IL12B	0.018	0.06	0.27	6	-0.34	1	7
STAT1 (dimer)	-0.13	0.49	0.65	1	-1.3	54	55
CD4	-0.12	0.45	0.68	4	-1.2	53	57
IL23	-0.092	0.45	0.69	4	-1.1	50	54
IL23R	0.004	0.17	-10000	0	-1	8	8
IL1B	-0.12	0.5	0.73	3	-1.3	56	59
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.1	0.44	0.73	3	-1.1	48	51
TYK2	0.015	0.042	-10000	0	-10000	0	0
STAT4	0.021	0.002	-10000	0	-10000	0	0
STAT3	0.021	0.003	-10000	0	-10000	0	0
IL18RAP	0.008	0.068	-10000	0	-0.32	20	20
IL12RB1	0.007	0.07	-10000	0	-0.36	12	12
PIK3CA	0.021	0.004	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	0.017	0.065	0.2	1	-0.26	11	12
IL23R/JAK2	0.015	0.17	-10000	0	-0.96	8	8
positive regulation of chronic inflammatory response	-0.13	0.52	0.74	3	-1.4	53	56
natural killer cell activation	0	0.01	-10000	0	-0.046	2	2
JAK2	0.015	0.055	0.19	1	-0.34	2	3
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
NFKB1	0.013	0.021	-10000	0	-10000	0	0
RELA	0.013	0.021	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.084	0.43	0.68	5	-1.1	50	55
ALOX12B	-0.1	0.44	0.73	2	-1.1	49	51
CXCL1	-0.13	0.47	0.72	3	-1.2	60	63
T cell proliferation	-0.13	0.52	0.74	3	-1.4	53	56
NFKBIA	0.011	0.02	-10000	0	-10000	0	0
IL17A	-0.028	0.26	0.49	23	-0.56	44	67
PI3K	-0.12	0.47	0.62	1	-1.2	53	54
IFNG	0.006	0.047	0.14	24	-0.13	10	34
STAT3 (dimer)	-0.11	0.45	0.62	3	-1.2	53	56
IL18R1	0.006	0.071	-10000	0	-0.32	22	22
IL23/IL23R/JAK2/TYK2/SOCS3	-0.07	0.35	0.52	7	-0.91	42	49
IL18/IL18R	0.025	0.086	-10000	0	-0.24	39	39
macrophage activation	-0.004	0.024	0.051	31	-0.045	22	53
TNF	-0.12	0.48	0.73	4	-1.2	54	58
STAT3/STAT4	-0.12	0.47	0.62	1	-1.2	53	54
STAT4 (dimer)	-0.13	0.49	0.65	1	-1.3	54	55
IL18	0.013	0.049	-10000	0	-0.33	10	10
IL19	-0.098	0.44	0.7	3	-1.1	50	53
STAT5A (dimer)	-0.13	0.49	0.65	1	-1.3	53	54
STAT1	0.021	0.002	-10000	0	-10000	0	0
SOCS3	0.018	0.031	-10000	0	-0.33	4	4
CXCL9	-0.12	0.47	0.69	4	-1.2	58	62
MPO	-0.12	0.46	0.67	2	-1.2	60	62
positive regulation of humoral immune response	-0.13	0.52	0.74	3	-1.4	53	56
IL23/IL23R/JAK2/TYK2	-0.15	0.56	0.74	3	-1.5	53	56
IL6	-0.21	0.58	0.69	2	-1.2	122	124
STAT5A	0.02	0.016	-10000	0	-0.33	1	1
IL2	0.013	0.027	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0	0.01	-10000	0	-0.046	2	2
CD3E	-0.12	0.45	0.67	2	-1.1	55	57
keratinocyte proliferation	-0.13	0.52	0.74	3	-1.4	53	56
NOS2	-0.16	0.51	0.7	3	-1.2	77	80

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.02	0.038	-10000	0	-0.2	21	21
ADCY5	-0.033	0.063	0.091	8	-0.2	61	69
ADCY6	-0.015	0.018	-10000	0	-0.19	5	5
ADCY7	-0.014	0.018	-10000	0	-0.19	5	5
ADCY1	-0.012	0.027	0.16	6	-0.19	5	11
ADCY2	-0.02	0.052	0.12	12	-0.19	36	48
ADCY3	-0.015	0.017	-10000	0	-0.19	5	5
ADCY8	-0.071	0.086	0.091	1	-0.19	170	171
PRKCE	-0.01	0.021	-10000	0	-0.22	5	5
ADCY9	-0.017	0.028	-10000	0	-0.19	13	13
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	-0.004	0.1	0.2	54	-0.24	13	67

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	0.023	0.04	-10000	0	-0.23	12	12
alphaV beta3 Integrin	0.016	0.093	0.22	21	-0.2	69	90
PTK2	-0.042	0.12	0.33	10	-0.36	26	36
IGF1R	0.02	0.004	-10000	0	-10000	0	0
PI4KB	0.018	0.008	-10000	0	-10000	0	0
MFGE8	0.021	0.003	-10000	0	-10000	0	0
SRC	0.02	0.004	-10000	0	-10000	0	0
CDKN1B	-0.058	0.16	-10000	0	-0.41	81	81
VEGFA	0.021	0.004	-10000	0	-10000	0	0
ILK	-0.06	0.16	0.18	6	-0.4	85	91
ROCK1	0.02	0.005	-10000	0	-10000	0	0
AKT1	-0.068	0.14	-10000	0	-0.38	84	84
PTK2B	-0.013	0.053	0.17	26	-0.32	1	27
alphaV/beta3 Integrin/JAM-A	-0.004	0.11	0.22	25	-0.2	97	122
CBL	0.02	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.054	0.059	0.22	47	-0.19	5	52
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.046	0.04	0.23	1	-0.19	11	12
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.024	0.085	0.16	2	-0.31	16	18
alphaV/beta3 Integrin/Syndecan-1	0.047	0.046	0.22	23	-0.2	5	28
PI4KA	0.02	0.005	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.016	0.091	-10000	0	-0.2	61	61
PI4 Kinase	0.025	0.013	-10000	0	-10000	0	0
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	0.17	0.11	0.24	341	-0.18	5	346
RPS6KB1	-0.046	0.072	0.32	3	-0.36	7	10
TLN1	0.019	0.016	-10000	0	-0.33	1	1
MAPK3	-0.057	0.14	0.28	1	-0.43	56	57
GPR124	0.017	0.023	-10000	0	-0.33	2	2
MAPK1	-0.057	0.14	0.28	1	-0.43	58	59
PXN	0.021	0.003	-10000	0	-10000	0	0
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
alphaV/beta3 Integrin/Tumstatin	-0.014	0.11	0.22	19	-0.2	133	152
cell adhesion	0.04	0.053	0.22	23	-0.2	7	30
ANGPTL3	0.034	0.066	0.32	25	-10000	0	25
VEGFR2 homodimer/VEGFA homodimer/Src	0.034	0.036	-10000	0	-0.2	11	11
IGF-1R heterotetramer	0.02	0.004	-10000	0	-10000	0	0
Rac1/GDP	0.014	0.005	-10000	0	-10000	0	0
TGFBR2	0.014	0.048	-10000	0	-0.33	10	10
ITGB3	0.031	0.072	0.32	23	-0.33	5	28
IGF1	0.014	0.052	0.32	1	-0.33	11	12
RAC1	0.019	0.007	-10000	0	-10000	0	0
regulation of cell-matrix adhesion	0.04	0.05	0.22	21	-0.22	6	27
apoptosis	0.021	0.002	-10000	0	-10000	0	0
CD47	0.019	0.022	-10000	0	-0.33	2	2
alphaV/beta3 Integrin/CD47	0.046	0.049	0.22	23	-0.2	7	30
VCL	0.021	0.003	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Del1	0.026	0.082	0.23	20	-0.21	43	63
CSF1	0.018	0.027	-10000	0	-0.33	3	3
PIK3C2A	-0.06	0.16	0.23	1	-0.4	85	86
PI4 Kinase/Pyk2	-0.053	0.074	0.18	1	-0.28	17	18
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.049	0.059	0.23	22	-0.19	16	38
FAK1/Vinculin	-0.033	0.11	0.31	10	-0.3	24	34
alphaV beta3/Integrin/ppsTEM5	0.041	0.05	0.22	21	-0.22	6	27
RHOA	0.02	0.004	-10000	0	-10000	0	0
VTN	-0.033	0.14	0.32	7	-0.33	85	92
BCAR1	0.02	0.016	-10000	0	-0.33	1	1
FGF2	-0.027	0.12	-10000	0	-0.33	70	70
F11R	-0.035	0.064	-10000	0	-0.23	49	49
alphaV/beta3 Integrin/Lactadherin	0.047	0.046	0.22	23	-0.2	5	28
alphaV/beta3 Integrin/TGFBR2	0.042	0.056	0.22	23	-0.2	14	37
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.046	0.027	-10000	0	-0.18	4	4
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	0.043	0.045	0.21	22	-0.2	5	27
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.019	0.033	0.32	1	-0.33	4	5
alphaV/beta3 Integrin/Pyk2	0.031	0.058	0.21	20	-0.18	15	35
SDC1	0.021	0.002	-10000	0	-10000	0	0
VAV3	-0.019	0.045	0.17	21	-0.19	8	29
PTPN11	0.021	0.004	-10000	0	-10000	0	0
IRS1	0.02	0.016	-10000	0	-0.33	1	1
FAK1/Paxillin	-0.034	0.11	0.3	9	-0.3	26	35
cell migration	-0.035	0.1	0.27	11	-0.27	24	35
ITGAV	0.021	0.002	-10000	0	-10000	0	0
PI3K	0.003	0.1	0.28	1	-0.2	81	82
SPP1	0.23	0.14	0.32	351	-10000	0	351
KDR	0.012	0.053	-10000	0	-0.33	12	12
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.021	0.002	-10000	0	-10000	0	0
COL4A3	-0.069	0.15	-10000	0	-0.33	133	133
angiogenesis	-0.054	0.16	0.28	2	-0.45	54	56
Rac1/GTP	-0.019	0.041	0.16	19	-0.28	1	20
EDIL3	-0.008	0.096	0.32	1	-0.33	42	43
cell proliferation	0.041	0.056	0.22	23	-0.2	14	37

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.023	0.017	0.19	1	-10000	0	1
AES	0.021	0.014	0.16	1	-10000	0	1
FBXW11	0.02	0.005	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.029	0.01	-10000	0	-10000	0	0
SMAD4	0.019	0.007	-10000	0	-10000	0	0
DKK2	-0.05	0.14	-10000	0	-0.33	104	104
TLE1	0.022	0.014	0.17	1	-10000	0	1
MACF1	0.019	0.031	-10000	0	-0.32	4	4
CTNNB1	0.078	0.11	0.29	26	-0.34	8	34
WIF1	-0.21	0.16	-10000	0	-0.32	336	336
beta catenin/RanBP3	0.044	0.11	0.44	20	-0.33	4	24
KREMEN2	0.095	0.13	0.32	126	-10000	0	126
DKK1	0.037	0.16	0.32	82	-0.33	48	130
beta catenin/beta TrCP1	0.08	0.1	0.3	19	-0.32	7	26
FZD1	0.021	0.005	-10000	0	-10000	0	0
AXIN2	-0.029	0.25	0.58	18	-1.2	18	36
AXIN1	0.022	0.004	-10000	0	-10000	0	0
RAN	0.021	0.014	0.32	1	-10000	0	1
Axin1/APC/GSK3/beta catenin	0.027	0.096	-10000	0	-0.66	8	8
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.018	0.18	0.32	1	-0.58	30	31
Axin1/APC/GSK3	0.05	0.073	0.23	19	-0.32	5	24
Axin1/APC/GSK3/beta catenin/Macf1	0.033	0.085	0.26	15	-0.37	9	24
HNF1A	0.081	0.12	0.32	101	-0.33	1	102
CTBP1	0.023	0.015	0.18	1	-10000	0	1
MYC	0.072	0.23	0.55	81	-1.3	2	83
RANBP3	0.02	0.005	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.027	0.12	0.22	80	-0.17	98	178
NKD1	-0.016	0.11	0.32	4	-0.33	57	61
TCF4	0.019	0.026	0.17	1	-0.33	2	3
TCF3	0.022	0.015	0.18	1	-10000	0	1
WNT1/LRP6/FZD1/Axin1	0.051	0.029	0.23	7	-10000	0	7
Ran/GTP	0.016	0.009	0.22	1	-10000	0	1
CtBP/CBP/TCF/TLE1/AES	0.008	0.12	0.4	20	-0.47	10	30
LEF1	0.024	0.02	0.24	2	-10000	0	2
DVL1	0.039	0.055	-10000	0	-0.33	4	4
CSNK2A1	0.021	0.005	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.026	0.16	-10000	0	-0.59	23	23
DKK1/LRP6/Kremen 2	0.083	0.13	0.25	156	-0.18	46	202
LRP6	0.02	0.006	-10000	0	-10000	0	0
CSNK1A1	0.023	0.016	-10000	0	-10000	0	0
NLK	0.019	0.011	-10000	0	-10000	0	0
CCND1	-0.004	0.19	0.58	21	-1.2	7	28
WNT1	0.028	0.044	0.32	11	-10000	0	11
GSK3A	0.021	0.004	-10000	0	-10000	0	0
GSK3B	0.021	0.003	-10000	0	-10000	0	0
FRAT1	0.021	0.004	-10000	0	-10000	0	0
PPP2R5D	0.048	0.078	0.24	43	-0.25	3	46
APC	-0.003	0.061	0.19	43	-10000	0	43
WNT1/LRP6/FZD1	0.094	0.088	0.19	61	-0.19	4	65
CREBBP	0.023	0.015	0.18	1	-10000	0	1

Neurotrophic factor-mediated Trk 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
CRKL	0.02	0.005	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.023	0.07	-10000	0	-0.24	25	25
NT3 (dimer)/TRKC	-0.025	0.11	0.23	2	-0.25	102	104
NT3 (dimer)/TRKB	-0.045	0.13	0.3	7	-0.21	180	187
SHC/Grb2/SOS1/GAB1/PI3K	0.008	0.027	-10000	0	-0.19	2	2
RAPGEF1	0.021	0.004	-10000	0	-10000	0	0
BDNF	-0.15	0.17	-10000	0	-0.33	258	258
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
DYNLT1	0.019	0.006	-10000	0	-10000	0	0
NTRK1	0.01	0.056	0.32	1	-0.33	13	14
NTRK2	-0.095	0.17	0.32	3	-0.33	173	176
NTRK3	-0.045	0.14	-10000	0	-0.33	97	97
NT-4/5 (dimer)/TRKB	-0.047	0.13	0.29	6	-0.21	185	191
neuron apoptosis	0.14	0.16	0.4	112	-10000	0	112
SHC 2-3/Grb2	-0.16	0.18	-10000	0	-0.44	112	112
SHC1	0.018	0.016	0.32	1	-10000	0	1
SHC2	-0.11	0.15	-10000	0	-0.43	67	67
SHC3	-0.16	0.21	-10000	0	-0.52	112	112
STAT3 (dimer)	0.018	0.038	-10000	0	-0.3	7	7
NT3 (dimer)/TRKA	0.022	0.07	0.27	7	-0.2	34	41
RIN/GDP	-0.02	0.073	0.22	3	-0.22	15	18
GIPC1	0.02	0.005	-10000	0	-10000	0	0
KRAS	0.02	0.006	-10000	0	-10000	0	0
DNAJA3	-0.015	0.056	0.18	5	-0.21	24	29
RIN/GTP	0.013	0.013	0.22	2	-10000	0	2
CCND1	-0.022	0.067	-10000	0	-0.59	7	7
MAGED1	0.021	0.014	0.32	1	-10000	0	1
PTPN11	0.021	0.004	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.003	0.077	0.32	1	-0.32	26	27
SHC/GRB2/SOS1	0.035	0.017	-10000	0	-10000	0	0
GRB2	0.02	0.004	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	0.024	0.072	0.22	16	-0.2	34	50
TRKA/NEDD4-2	0.019	0.043	0.23	1	-0.23	13	14
ELMO1	0.018	0.022	-10000	0	-0.33	2	2
RhoG/GTP/ELMO1/DOCK1	0.025	0.016	-10000	0	-0.19	2	2
NGF	0.025	0.085	0.32	23	-0.33	13	36
HRAS	0.021	0.004	-10000	0	-10000	0	0
DOCK1	0.021	0.003	-10000	0	-10000	0	0
GAB2	0.017	0.034	-10000	0	-0.33	5	5
RIT2	0.017	0.02	0.32	2	-10000	0	2
RIT1	0.018	0.008	-10000	0	-10000	0	0
FRS2	0.02	0.005	-10000	0	-10000	0	0
DNM1	0.025	0.035	0.32	7	-10000	0	7
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.019	0.006	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	0.006	0.062	0.18	2	-0.21	25	27
mol:GDP	-0.033	0.1	0.27	3	-0.31	21	24
NGF (dimer)	0.025	0.085	0.32	23	-0.32	13	36
RhoG/GDP	0.013	0.015	-10000	0	-0.22	2	2
RIT1/GDP	-0.025	0.065	0.22	1	-0.23	13	14
TIAM1	0.015	0.043	-10000	0	-0.33	8	8
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
BDNF (dimer)/TRKB	-0.14	0.15	0.22	1	-0.24	329	330
KIDINS220/CRKL/C3G	0.029	0.009	-10000	0	-10000	0	0
SHC/RasGAP	0.025	0.013	-10000	0	-10000	0	0
FRS2 family/SHP2	0.039	0.014	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0.044	0.025	-10000	0	-0.18	1	1
RIT1/GTP	0.013	0.006	-10000	0	-10000	0	0
NT3 (dimer)	0.006	0.074	0.32	2	-0.32	23	25
RAP1/GDP	-0.022	0.061	-10000	0	-0.19	16	16
KIDINS220/CRKL	0.02	0.005	-10000	0	-10000	0	0
BDNF (dimer)	-0.15	0.17	-10000	0	-0.32	258	258
ubiquitin-dependent protein catabolic process	0.028	0.06	0.22	17	-0.19	22	39
Schwann cell development	-0.036	0.025	-10000	0	-10000	0	0
EHD4	0.02	0.005	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.048	0.021	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.004	0.049	-10000	0	-0.23	7	7
RAP1B	0.02	0.005	-10000	0	-10000	0	0
RAP1A	0.02	0.004	-10000	0	-10000	0	0
CDC42/GTP	-0.14	0.14	-10000	0	-0.24	305	305
ABL1	0.021	0.004	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.03	0.007	-10000	0	-10000	0	0
Rap1/GTP	-0.074	0.1	-10000	0	-0.4	26	26
STAT3	0.018	0.038	-10000	0	-0.3	7	7
axon guidance	-0.16	0.12	-10000	0	-0.31	151	151
MAPK3	-0.011	0.074	0.18	42	-0.2	28	70
MAPK1	-0.01	0.072	0.18	40	-0.19	24	64
CDC42/GDP	-0.02	0.074	0.22	3	-0.22	13	16
NTF3	0.006	0.075	0.32	2	-0.33	23	25
NTF4	0.003	0.077	0.32	1	-0.33	26	27
NGF (dimer)/TRKA/FAIM	0.033	0.061	0.22	19	-0.19	21	40
PI3K	0.029	0.014	-10000	0	-0.23	1	1
FRS3	0.02	0.004	-10000	0	-10000	0	0
FAIM	0.021	0.003	-10000	0	-10000	0	0
GAB1	0.02	0.022	-10000	0	-0.33	2	2
RASGRF1	-0.06	0.089	0.15	1	-0.26	39	40
SOS1	0.021	0.003	-10000	0	-10000	0	0
MCF2L	-0.052	0.081	0.17	3	-0.21	93	96
RGS19	0.019	0.006	-10000	0	-10000	0	0
CDC42	0.021	0.003	-10000	0	-10000	0	0
RAS family/GTP	0	0.077	0.31	2	-0.39	4	6
Rac1/GDP	-0.021	0.07	-10000	0	-0.23	15	15
NGF (dimer)/TRKA/GRIT	0.022	0.057	0.21	19	-0.18	22	41
neuron projection morphogenesis	0.004	0.1	-10000	0	-0.88	3	3
NGF (dimer)/TRKA/NEDD4-2	0.029	0.061	0.22	17	-0.19	22	39
MAP2K1	0.012	0.091	0.2	88	-0.17	1	89
NGFR	0.019	0.058	0.32	7	-0.33	9	16
NGF (dimer)/TRKA/GIPC/GAIP	0	0.061	0.18	7	-0.21	26	33
RAS family/GTP/PI3K	0.01	0.02	0.15	1	-0.17	5	6
FRS2 family/SHP2/GRB2/SOS1	0.054	0.025	-10000	0	-10000	0	0
NRAS	0.02	0.005	-10000	0	-10000	0	0
GRB2/SOS1	0.03	0.007	-10000	0	-10000	0	0
PRKCI	0.02	0.005	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.019	0.007	-10000	0	-10000	0	0
PRKCZ	0.019	0.027	-10000	0	-0.33	3	3
MAPKKK cascade	-0.065	0.18	-10000	0	-0.56	55	55
RASA1	0.02	0.005	-10000	0	-10000	0	0
TRKA/c-Abl	0.02	0.043	0.23	1	-0.23	13	14
SQSTM1	0.02	0.005	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.13	0.14	0.23	2	-0.22	329	331
NGF (dimer)/TRKA/p62/Atypical PKCs	0.043	0.063	0.22	16	-0.18	21	37
MATK	0.009	0.06	-10000	0	-0.33	16	16
NEDD4L	0.019	0.007	-10000	0	-10000	0	0
RAS family/GDP	-0.029	0.045	-10000	0	-0.17	17	17
NGF (dimer)/TRKA	0	0.061	0.18	5	-0.21	26	31
Rac1/GTP	-0.061	0.07	-10000	0	-0.21	57	57
FRS2 family/SHP2/CRK family	0.049	0.029	-10000	0	-10000	0	0

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0.007	0.097	-10000	0	-0.41	23	23
HDAC1	0.021	0.006	-10000	0	-10000	0	0
AES	0.02	0.006	-10000	0	-10000	0	0
FBXW11	0.02	0.005	-10000	0	-10000	0	0
DTX1	0.022	0.019	0.32	2	-10000	0	2
LRP6/FZD1	0.028	0.01	-10000	0	-10000	0	0
TLE1	0.02	0.005	-10000	0	-10000	0	0
AP1	-0.023	0.084	-10000	0	-0.24	57	57
NCSTN	0.019	0.007	-10000	0	-10000	0	0
ADAM10	0.021	0.004	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.02	0.1	-10000	0	-0.71	7	7
NICD/RBPSUH	0.006	0.098	-10000	0	-0.41	23	23
WIF1	-0.21	0.16	-10000	0	-0.33	336	336
NOTCH1	-0.003	0.087	-10000	0	-0.43	20	20
PSENEN	0.02	0.005	-10000	0	-10000	0	0
KREMEN2	0.095	0.13	0.32	126	-10000	0	126
DKK1	0.037	0.16	0.32	82	-0.33	48	130
beta catenin/beta TrCP1	0.012	0.076	0.3	1	-0.34	2	3
APH1B	0.019	0.022	-10000	0	-0.33	2	2
APH1A	0.017	0.008	-10000	0	-10000	0	0
AXIN1	0.001	0.071	-10000	0	-0.42	7	7
CtBP/CBP/TCF1/TLE1/AES	0.022	0.055	0.25	2	-10000	0	2
PSEN1	0.021	0.004	-10000	0	-10000	0	0
FOS	0.002	0.078	-10000	0	-0.33	27	27
JUN	0.019	0.027	-10000	0	-0.33	3	3
MAP3K7	0.019	0.006	-10000	0	-10000	0	0
CTNNB1	0.008	0.076	0.27	2	-0.3	4	6
MAPK3	0.021	0.003	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.027	0.12	0.22	80	-0.17	98	178
HNF1A	0.079	0.12	0.32	100	-0.33	1	101
CTBP1	0.02	0.005	-10000	0	-10000	0	0
MYC	0.008	0.079	-10000	0	-1.2	2	2
NKD1	-0.016	0.11	0.32	4	-0.33	57	61
FZD1	0.02	0.004	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	0.008	0.097	-10000	0	-0.42	22	22
apoptosis	-0.022	0.084	-10000	0	-0.23	57	57
Delta 1/NOTCHprecursor	0.004	0.097	-10000	0	-0.41	23	23
DLL1	0.015	0.041	-10000	0	-0.33	7	7
PPARD	0.015	0.041	-10000	0	-0.84	1	1
Gamma Secretase	0.046	0.031	-10000	0	-0.18	1	1
APC	-0.009	0.095	-10000	0	-0.4	20	20
DVL1	-0.033	0.073	-10000	0	-0.29	30	30
CSNK2A1	0.02	0.006	-10000	0	-10000	0	0
MAP3K7IP1	0	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	0.083	0.13	0.25	156	-0.18	46	202
LRP6	0.02	0.005	-10000	0	-10000	0	0
CSNK1A1	0.02	0.006	-10000	0	-10000	0	0
NLK	0.007	0.006	-10000	0	-10000	0	0
CCND1	-0.002	0.15	-10000	0	-1.1	9	9
WNT1	0.027	0.044	0.32	11	-10000	0	11
Axin1/APC/beta catenin	0.004	0.11	0.29	8	-0.42	13	21
DKK2	-0.05	0.14	-10000	0	-0.33	104	104
NOTCH1 precursor/DVL1	-0.032	0.11	-10000	0	-0.46	23	23
GSK3B	0.021	0.003	-10000	0	-10000	0	0
FRAT1	0.021	0.003	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	0.011	0.097	-10000	0	-0.42	22	22
PPP2R5D	0.01	0.075	0.24	2	-0.32	9	11
MAPK1	0.02	0.005	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.094	0.11	0.23	3	-0.18	312	315
RBPJ	0.021	0.004	-10000	0	-10000	0	0
CREBBP	0.021	0.005	-10000	0	-10000	0	0

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.021	0.004	-10000	0	-10000	0	0
EGFR	0.014	0.045	0.32	1	-0.33	8	9
EGF/EGFR	0.024	0.089	0.18	58	-0.17	58	116
EGF/EGFR dimer/SHC/GRB2/SOS1	0.061	0.074	0.23	57	-0.19	8	65
mol:GTP	0	0	-10000	0	-10000	0	0
EDNRA	0.02	0.016	-10000	0	-0.33	1	1
response to oxidative stress	0	0	-10000	0	-10000	0	0
EGF	0.071	0.12	0.32	91	-0.33	5	96
EGF/EGFR dimer/SHC	0.048	0.074	0.23	58	-0.2	10	68
mol:GDP	0.055	0.069	0.21	57	-0.19	8	65
mol:Ca2+	0	0	-10000	0	-10000	0	0
EDN1	-0.027	0.12	-10000	0	-0.33	71	71
GRB2/SOS1	0.03	0.007	-10000	0	-10000	0	0
HRAS/GTP	0.035	0.049	0.22	1	-0.18	7	8
SHC1	0.018	0.016	0.32	1	-10000	0	1
HRAS/GDP	0.049	0.06	0.28	1	-0.19	7	8
FRAP1	-0.013	0.036	0.16	6	-0.18	8	14
EGF/EGFR dimer	0.051	0.087	0.24	75	-0.23	12	87
SOS1	0.021	0.003	-10000	0	-10000	0	0
GRB2	0.02	0.004	-10000	0	-10000	0	0
ETA receptor/Endothelin-1	-0.006	0.09	-10000	0	-0.23	72	72

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	0.007	0.08	-10000	0	-0.2	65	65
fibroblast growth factor receptor signaling pathway	0.007	0.079	-10000	0	-0.2	65	65
LAMA1	0.024	0.066	0.32	15	-0.33	7	22
PRNP	0.019	0.022	-10000	0	-0.33	2	2
GPC1/SLIT2	-0.035	0.11	-10000	0	-0.23	127	127
SMAD2	-0.022	0.026	0.17	2	-0.18	8	10
GPC1/PrPc/Cu2+	0.025	0.02	-10000	0	-0.18	4	4
GPC1/Laminin alpha1	0.03	0.05	0.23	14	-0.22	10	24
TDGF1	0.023	0.074	0.32	17	-0.33	10	27
CRIPTO/GPC1	0.03	0.056	0.23	17	-0.23	13	30
APP/GPC1	0.028	0.022	-10000	0	-0.23	3	3
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.018	0.034	0.1	15	-0.2	11	26
FLT1	0.02	0.005	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	0.035	0.038	0.22	1	-0.19	12	13
SERPINC1	0.023	0.036	0.32	7	-10000	0	7
FYN	-0.018	0.037	0.1	16	-0.21	11	27
FGR	-0.03	0.058	0.1	15	-0.21	40	55
positive regulation of MAPKKK cascade	-0.019	0.098	0.2	9	-0.32	33	42
SLIT2	-0.066	0.15	-10000	0	-0.33	128	128
GPC1/NRG	-0.018	0.098	-10000	0	-0.23	85	85
NRG1	-0.04	0.13	-10000	0	-0.33	85	85
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.037	0.022	-10000	0	-0.2	3	3
LYN	-0.017	0.034	-10000	0	-0.2	10	10
mol:Spermine	-0.01	0.016	-10000	0	-0.22	3	3
cell growth	0.007	0.079	-10000	0	-0.2	65	65
BMP signaling pathway	-0.019	0.027	0.32	3	-10000	0	3
SRC	-0.019	0.035	0.1	16	-0.2	12	28
TGFBR1	0.021	0.014	0.32	1	-10000	0	1
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.013	0.13	0.32	17	-0.33	64	81
GPC1	0.019	0.027	-10000	0	-0.33	3	3
TGFBR1 (dimer)	0.021	0.014	0.32	1	-10000	0	1
VEGFA	0.021	0.004	-10000	0	-10000	0	0
BLK	0.012	0.076	0.16	92	-0.2	11	103
HCK	-0.025	0.047	0.1	15	-0.19	31	46
FGF2	-0.027	0.12	-10000	0	-0.33	70	70
FGFR1	0.018	0.017	-10000	0	-0.33	1	1
VEGFR1 homodimer	0.02	0.005	-10000	0	-10000	0	0
TGFBR2	0.014	0.048	-10000	0	-0.33	10	10
cell death	0.027	0.022	-10000	0	-0.23	3	3
ATIII/GPC1	0.029	0.033	0.23	7	-0.23	3	10
PLA2G2A/GPC1	0.004	0.097	0.23	17	-0.23	64	81
LCK	-0.019	0.038	0.11	18	-0.2	14	32
neuron differentiation	-0.018	0.097	-10000	0	-0.23	85	85
PrPc/Cu2+	0.014	0.015	-10000	0	-0.22	2	2
APP	0.02	0.005	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.014	0.048	-10000	0	-0.32	10	10

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.034	0.032	0.23	12	-10000	0	12
VLDLR	0.014	0.043	-10000	0	-0.33	8	8
CRKL	0.02	0.005	-10000	0	-10000	0	0
LRPAP1	0.021	0.004	-10000	0	-10000	0	0
FYN	0.019	0.016	-10000	0	-0.33	1	1
ITGA3	0.017	0.034	-10000	0	-0.33	5	5
RELN/VLDLR/Fyn	0.006	0.083	0.22	5	-0.2	66	71
MAPK8IP1/MKK7/MAP3K11/JNK1	0.049	0.029	-10000	0	-0.18	1	1
AKT1	-0.033	0.074	0.2	3	-0.21	58	61
MAP2K7	0.02	0.005	-10000	0	-10000	0	0
RAPGEF1	0.021	0.004	-10000	0	-10000	0	0
DAB1	0.023	0.036	0.32	7	-10000	0	7
RELN/LRP8/DAB1	0.018	0.079	0.22	18	-0.17	61	79
LRPAP1/LRP8	0.034	0.028	0.23	9	-10000	0	9
RELN/LRP8/DAB1/Fyn	0.022	0.078	0.22	16	-0.17	60	76
DAB1/alpha3/beta1 Integrin	0.014	0.077	0.27	1	-0.18	57	58
long-term memory	0.009	0.1	0.25	14	-0.18	86	100
DAB1/LIS1	0.023	0.084	0.35	1	-0.18	57	58
DAB1/CRLK/C3G	0.015	0.076	0.27	1	-0.18	54	55
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
DAB1/NCK2	0.027	0.084	0.35	1	-0.17	59	60
ARHGEF2	0.018	0.008	-10000	0	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	0.009	0.14	0.32	42	-0.33	53	95
CDK5R1	0.028	0.048	0.32	13	-10000	0	13
RELN	-0.018	0.12	0.32	6	-0.33	62	68
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
RELN/LRP8/Fyn	0.013	0.084	0.22	13	-0.19	63	76
GRIN2A/RELN/LRP8/DAB1/Fyn	0.021	0.11	0.23	42	-0.18	90	132
MAPK8	0.021	0.003	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	0.011	0.079	0.23	10	-0.18	64	74
ITGB1	0.021	0.004	-10000	0	-10000	0	0
MAP1B	-0.027	0.075	0.22	9	-0.19	55	64
RELN/LRP8	0.015	0.084	0.22	13	-0.2	62	75
GRIN2B/RELN/LRP8/DAB1/Fyn	0.03	0.088	0.25	20	-0.17	59	79
PI3K	0.029	0.014	-10000	0	-0.23	1	1
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.027	0.027	-10000	0	-0.23	5	5
RAP1A	-0.028	0.079	0.28	7	-0.28	3	10
PAFAH1B1	0.019	0.006	-10000	0	-10000	0	0
MAPK8IP1	0.021	0.003	-10000	0	-10000	0	0
CRLK/C3G	0.029	0.009	-10000	0	-10000	0	0
GRIN2B	0.023	0.041	0.32	9	-10000	0	9
NCK2	0.021	0.002	-10000	0	-10000	0	0
neuron differentiation	-0.007	0.073	0.24	2	-0.29	12	14
neuron adhesion	-0.03	0.088	0.32	10	-0.28	4	14
LRP8	0.027	0.042	0.32	10	-10000	0	10
GSK3B	-0.035	0.071	0.18	3	-0.21	59	62
RELN/VLDLR/DAB1/Fyn	0.016	0.078	0.23	8	-0.17	63	71
MAP3K11	0.02	0.016	-10000	0	-0.33	1	1
RELN/VLDLR/DAB1/P13K	-0.016	0.081	0.18	3	-0.22	64	67
CDK5	0.02	0.005	-10000	0	-10000	0	0
MAPT	-0.005	0.12	0.77	8	-0.29	22	30
neuron migration	-0.037	0.099	0.23	12	-0.26	53	65
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.005	0.07	0.24	2	-0.27	10	12
RELN/VLDLR	0.02	0.087	0.23	12	-0.18	65	77

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	0.04	0.075	0.16	140	-10000	0	140
TP53	0.011	0.037	-10000	0	-0.12	17	17
Senescence	0.011	0.037	-10000	0	-0.12	17	17
Apoptosis	0.011	0.037	-10000	0	-0.12	17	17
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	-0.022	0.075	0.25	22	-0.19	5	27
MDM4	0.019	0.006	-10000	0	-10000	0	0

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.012	0.28	0.57	24	-0.63	10	34
CRP	0.029	0.29	0.58	38	-0.67	9	47
cell cycle arrest	0.001	0.3	0.55	34	-0.62	31	65
TIMP1	0.018	0.26	0.55	24	-0.61	13	37
IL6ST	0.003	0.072	-10000	0	-0.32	20	20
Rac1/GDP	-0.004	0.15	0.31	19	-0.32	36	55
AP1	0.056	0.13	0.39	7	-0.46	8	15
GAB2	0.019	0.035	-10000	0	-0.32	5	5
TNFSF11	0.036	0.3	0.58	40	-0.65	10	50
HSP90B1	0.023	0.15	-10000	0	-0.72	10	10
GAB1	0.021	0.022	-10000	0	-0.32	2	2
MAPK14	-0.028	0.11	0.27	3	-0.45	12	15
AKT1	0.013	0.086	0.27	2	-0.64	5	7
FOXO1	0.01	0.084	0.32	2	-0.6	5	7
MAP2K6	-0.018	0.12	0.26	14	-0.31	36	50
mol:GTP	0	0.004	-10000	0	-10000	0	0
MAP2K4	-0.001	0.18	0.36	28	-0.37	32	60
MITF	-0.008	0.13	0.26	28	-0.3	40	68
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.02	0.005	-10000	0	-10000	0	0
A2M	-0.12	0.38	-10000	0	-1.2	59	59
CEBPB	0.024	0.01	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.018	0.088	0.29	3	-0.38	6	9
STAT3	-0.003	0.31	0.58	26	-0.65	31	57
STAT1	0.023	0.037	-10000	0	-10000	0	0
CEBPD	0.018	0.29	0.59	27	-0.73	10	37
PIK3CA	0.021	0.005	-10000	0	-10000	0	0
PI3K	0.029	0.015	-10000	0	-0.23	1	1
JUN	0.019	0.027	-10000	0	-0.33	3	3
PIAS3/MITF	-0.007	0.13	0.28	14	-0.3	35	49
MAPK11	-0.026	0.1	0.27	3	-0.45	12	15
STAT3 (dimer)/FOXO1	-0.019	0.26	0.48	28	-0.61	17	45
GRB2/SOS1/GAB family	0.004	0.12	0.28	4	-0.31	24	28
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.021	0.11	0.24	4	-0.26	67	71
GRB2	0.022	0.006	-10000	0	-10000	0	0
JAK2	0.018	0.023	-10000	0	-0.33	2	2
LBP	0.052	0.27	0.54	57	-0.6	10	67
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
JAK1	0.013	0.025	-10000	0	-10000	0	0
MYC	0.031	0.29	0.6	31	-0.7	9	40
FGG	-0.15	0.51	0.6	31	-0.89	149	180
macrophage differentiation	0.001	0.3	0.55	34	-0.62	31	65
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0.001	0.099	0.26	1	-0.21	53	54
JUNB	0.002	0.27	0.54	22	-0.67	12	34
FOS	0.003	0.078	-10000	0	-0.33	27	27
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.006	0.14	0.28	28	-0.31	42	70
STAT1/PIAS1	0.013	0.16	0.34	31	-0.32	33	64
GRB2/SOS1/GAB family/SHP2/PI3K	0.016	0.086	-10000	0	-0.55	7	7
STAT3 (dimer)	-0.002	0.31	0.57	30	-0.64	31	61
PRKCD	0.017	0.23	0.43	47	-0.44	29	76
IL6R	0.005	0.049	-10000	0	-0.32	9	9
SOCS3	-0.026	0.13	-10000	0	-0.96	5	5
gp130 (dimer)/JAK1/JAK1/LMO4	0.028	0.073	0.24	2	-0.19	16	18
Rac1/GTP	-0.003	0.16	0.31	26	-0.34	36	62
HCK	0.006	0.069	-10000	0	-0.32	22	22
MAPKKK cascade	0.034	0.11	0.34	1	-0.51	7	8
bone resorption	0.039	0.3	0.57	42	-0.62	10	52
IRF1	0.006	0.28	0.56	22	-0.66	10	32
mol:GDP	-0.003	0.13	0.27	30	-0.31	37	67
SOS1	0.023	0.007	-10000	0	-10000	0	0
VAV1	-0.005	0.13	0.27	30	-0.31	37	67
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.023	0.11	-10000	0	-0.43	20	20
PTPN11	0.011	0.1	-10000	0	-0.7	9	9
IL6/IL6RA	-0.018	0.1	0.17	1	-0.23	81	82
gp130 (dimer)/TYK2/TYK2/LMO4	0.026	0.063	0.2	1	-0.18	21	22
gp130 (dimer)/JAK2/JAK2/LMO4	0.024	0.061	0.2	1	-0.18	19	20
IL6	-0.049	0.14	-10000	0	-0.32	101	101
PIAS3	0.018	0.008	-10000	0	-10000	0	0
PTPRE	-0.002	0.043	-10000	0	-0.24	4	4
PIAS1	0.021	0.004	-10000	0	-10000	0	0
RAC1	0.019	0.01	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.022	0.11	0.2	7	-0.26	63	70
LMO4	0.017	0.035	-10000	0	-0.29	1	1
STAT3 (dimer)/PIAS3	-0.026	0.27	0.52	19	-0.61	31	50
MCL1	0.037	0.11	0.42	4	-0.58	4	8

Glucocorticoid receptor regulatory network

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
PCK2	0.026	0.083	0.28	2	-0.33	1	3
SMARCC2	0.021	0.009	-10000	0	-0.17	1	1
SMARCC1	0.021	0.007	-10000	0	-10000	0	0
TBX21	-0.04	0.17	0.39	6	-0.55	31	37
SUMO2	0.019	0.012	-10000	0	-10000	0	0
STAT1 (dimer)	0.023	0.002	-10000	0	-10000	0	0
FKBP4	0.02	0.005	-10000	0	-10000	0	0
FKBP5	0.021	0.004	-10000	0	-10000	0	0
GR alpha/HSP90/FKBP51/HSP90	0.046	0.11	0.28	27	-10000	0	27
PRL	-0.019	0.11	0.49	1	-0.57	1	2
cortisol/GR alpha (dimer)/TIF2	0.059	0.21	0.52	43	-0.36	6	49
RELA	-0.038	0.1	-10000	0	-0.2	109	109
FGG	0.025	0.28	0.52	67	-0.42	58	125
GR beta/TIF2	0.034	0.11	0.3	25	-0.25	2	27
IFNG	-0.055	0.26	0.43	12	-0.68	41	53
apoptosis	0.011	0.13	0.5	9	-0.48	8	17
CREB1	0.04	0.046	0.2	1	-10000	0	1
histone acetylation	-0.071	0.12	-10000	0	-0.34	38	38
BGLAP	-0.017	0.1	-10000	0	-0.41	2	2
GR/PKAc	0.049	0.11	0.3	21	-10000	0	21
NF kappa B1 p50/RelA	-0.068	0.18	0.29	1	-0.32	144	145
SMARCD1	0.021	0.006	-10000	0	-10000	0	0
MDM2	0.035	0.086	0.23	46	-10000	0	46
GATA3	0.021	0.021	0.32	1	-0.33	1	2
AKT1	0.019	0.004	-10000	0	-10000	0	0
CSF2	-0.12	0.27	-10000	0	-0.93	44	44
GSK3B	0.019	0.012	-10000	0	-10000	0	0
NR1I3	0.024	0.13	0.48	9	-0.47	3	12
CSN2	0.051	0.18	0.39	46	-0.33	6	52
BRG1/BAF155/BAF170/BAF60A	0.049	0.027	-10000	0	-0.26	2	2
NFATC1	0.018	0.027	-10000	0	-0.33	3	3
POU2F1	0.022	0.017	-10000	0	-10000	0	0
CDKN1A	-0.005	0.067	-10000	0	-1	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	0.025	0.043	0.32	9	-0.33	1	10
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.056	0.1	0.29	20	-10000	0	20
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.01	0.19	0.46	8	-0.68	26	34
JUN	-0.013	0.18	0.33	32	-0.39	37	69
IL4	-0.034	0.12	-10000	0	-0.48	12	12
CDK5R1	0.027	0.049	0.32	13	-10000	0	13
PRKACA	0.02	0.005	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.042	0.066	0.17	3	-0.23	26	29
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.051	0.1	0.3	17	-10000	0	17
cortisol/GR alpha (monomer)	0.085	0.27	0.62	58	-0.42	6	64
NCOA2	0.016	0.035	-10000	0	-0.33	5	5
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	0.011	0.11	0.23	12	-0.28	25	37
AP-1/NFAT1-c-4	-0.009	0.27	0.42	34	-0.48	61	95
AFP	-0.014	0.17	0.44	8	-0.49	3	11
SUV420H1	0.021	0.004	-10000	0	-10000	0	0
IRF1	0.051	0.14	0.4	19	-10000	0	19
TP53	0.021	0.042	-10000	0	-0.91	1	1
PPP5C	0.02	0.005	-10000	0	-10000	0	0
KRT17	-0.06	0.3	0.44	24	-0.75	49	73
KRT14	0.037	0.18	0.47	5	-0.47	1	6
TBP	0.021	0.007	-10000	0	-10000	0	0
CREBBP	-0.019	0.07	-10000	0	-0.27	1	1
HDAC1	0.021	0.002	-10000	0	-10000	0	0
HDAC2	0.023	0.023	-10000	0	-10000	0	0
AP-1	-0.009	0.27	0.42	34	-0.48	62	96
MAPK14	0.019	0.012	-10000	0	-10000	0	0
MAPK10	-0.017	0.11	-10000	0	-0.33	55	55
MAPK11	0.017	0.025	-10000	0	-0.33	2	2
KRT5	-0.2	0.45	0.44	18	-0.91	136	154
interleukin-1 receptor activity	0.005	0.021	-10000	0	-10000	0	0
NCOA1	0.021	0.003	-10000	0	-10000	0	0
STAT1	0.023	0.002	-10000	0	-10000	0	0
CGA	-0.001	0.13	0.35	11	-0.39	9	20
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.004	0.17	0.47	33	-0.34	8	41
MAPK3	0.02	0.012	-10000	0	-10000	0	0
MAPK1	0.019	0.012	-10000	0	-10000	0	0
ICAM1	-0.1	0.21	-10000	0	-0.56	56	56
NFKB1	-0.04	0.1	-10000	0	-0.2	108	108
MAPK8	-0.019	0.16	0.3	15	-0.36	43	58
MAPK9	0.019	0.012	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.01	0.14	0.5	9	-0.49	9	18
BAX	-0.009	0.056	-10000	0	-10000	0	0
POMC	-0.12	0.28	-10000	0	-1	28	28
EP300	-0.018	0.07	-10000	0	-0.27	1	1
cortisol/GR alpha (dimer)/p53	0.07	0.22	0.53	51	-0.37	3	54
proteasomal ubiquitin-dependent protein catabolic process	0.02	0.074	0.21	35	-10000	0	35
SGK1	-0.028	0.11	-10000	0	-0.93	2	2
IL13	-0.05	0.2	-10000	0	-0.62	17	17
IL6	-0.21	0.37	-10000	0	-0.8	129	129
PRKACG	0.017	0.004	-10000	0	-10000	0	0
IL5	-0.048	0.17	-10000	0	-0.62	10	10
IL2	-0.059	0.23	0.38	6	-0.59	40	46
CDK5	0.019	0.01	-10000	0	-10000	0	0
PRKACB	0.021	0.014	0.32	1	-10000	0	1
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
IL8	-0.09	0.2	0.32	7	-0.48	59	66
CDK5R1/CDK5	0.033	0.034	0.24	12	-10000	0	12
NF kappa B1 p50/RelA/PKAc	-0.03	0.15	-10000	0	-0.27	101	101
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.07	0.21	0.51	48	-0.34	6	54
SMARCA4	0.02	0.016	-10000	0	-0.33	1	1
chromatin remodeling	0.042	0.13	0.36	28	-10000	0	28
NF kappa B1 p50/RelA/Cbp	-0.074	0.16	0.37	1	-0.36	66	67
JUN (dimer)	-0.013	0.18	0.33	32	-0.39	36	68
YWHAH	0.02	0.004	-10000	0	-10000	0	0
VIPR1	-0.25	0.34	-10000	0	-0.68	193	193
NR3C1	0.055	0.17	0.43	42	-10000	0	42
NR4A1	-0.059	0.16	-10000	0	-0.35	111	111
TIF2/SUV420H1	0.025	0.027	-10000	0	-0.23	5	5
MAPKKK cascade	0.011	0.13	0.5	9	-0.48	8	17
cortisol/GR alpha (dimer)/Src-1	0.078	0.23	0.53	55	-0.36	6	61
PBX1	0.014	0.055	-10000	0	-0.33	12	12
POU1F1	0.021	0.023	0.43	1	-10000	0	1
SELE	-0.19	0.36	-10000	0	-0.84	106	106
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.042	0.13	0.36	28	-10000	0	28
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.07	0.21	0.51	48	-0.34	6	54
mol:cortisol	0.049	0.15	0.36	61	-0.22	6	67
MMP1	0.16	0.2	0.38	69	-0.73	8	77

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	-0.006	0.056	-10000	0	-10000	0	0
BIRC5	0.18	0.15	0.32	276	-10000	0	276
NFKBIA	0.002	0.079	0.28	29	-10000	0	29
CPEB1	-0.026	0.12	0.32	2	-0.33	70	72
AKT1	-0.013	0.048	0.29	4	-10000	0	4
NDEL1	0.02	0.006	-10000	0	-10000	0	0
Aurora A/BRCA1	-0.004	0.051	0.24	1	-10000	0	1
NDEL1/TACC3	0.001	0.055	0.28	1	-10000	0	1
GADD45A	0.021	0.003	-10000	0	-10000	0	0
GSK3B	-0.015	0.031	-10000	0	-10000	0	0
PAK1/Aurora A	-0.007	0.055	-10000	0	-10000	0	0
MDM2	0.02	0.005	-10000	0	-10000	0	0
JUB	0	0	-10000	0	-10000	0	0
TPX2	0.082	0.096	0.17	275	-10000	0	275
TP53	-0.002	0.053	0.21	1	-0.24	8	9
DLG7	-0.011	0.037	0.15	2	-10000	0	2
AURKAIP1	0.02	0.016	-10000	0	-0.33	1	1
ARHGEF7	0.02	0.005	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.002	0.058	0.3	1	-10000	0	1
G2/M transition of mitotic cell cycle	-0.005	0.05	0.24	1	-10000	0	1
AURKA	-0.005	0.055	0.19	2	-10000	0	2
AURKB	0.096	0.087	0.19	223	-10000	0	223
CDC25B	-0.002	0.043	-10000	0	-0.23	4	4
G2/M transition checkpoint	-0.013	0.039	-10000	0	-10000	0	0
mRNA polyadenylation	-0.029	0.078	0.35	1	-0.2	53	54
Aurora A/CPEB	-0.029	0.078	0.36	1	-0.2	53	54
Aurora A/TACC1/TRAP/chTOG	0.001	0.066	-10000	0	-0.22	7	7
BRCA1	0.021	0.014	0.32	1	-10000	0	1
centrosome duplication	-0.007	0.055	-10000	0	-10000	0	0
regulation of centrosome cycle	0.001	0.054	0.27	1	-10000	0	1
spindle assembly	0	0.065	-10000	0	-0.21	7	7
TDRD7	0.02	0.004	-10000	0	-10000	0	0
Aurora A/RasGAP/Survivin	0.11	0.099	0.25	83	-10000	0	83
CENPA	0.11	0.09	0.19	260	-10000	0	260
Aurora A/PP2A	-0.006	0.055	-10000	0	-10000	0	0
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	-0.006	0.046	0.19	3	-10000	0	3
negative regulation of DNA binding	-0.002	0.053	0.21	1	-0.24	8	9
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.029	0.009	-10000	0	-10000	0	0
RASA1	0.02	0.005	-10000	0	-10000	0	0
Ajuba/Aurora A	-0.013	0.039	-10000	0	-10000	0	0
mitotic prometaphase	-0.014	0.03	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.005	0.055	0.19	2	-10000	0	2
TACC1	0.007	0.062	-10000	0	-0.33	17	17
TACC3	0.022	0.019	0.32	2	-10000	0	2
Aurora A/Antizyme1	0.002	0.058	-10000	0	-0.17	1	1
Aurora A/RasGAP	-0.005	0.053	-10000	0	-10000	0	0
OAZ1	0.02	0.005	-10000	0	-10000	0	0
RAN	0.021	0.014	0.32	1	-10000	0	1
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	-0.015	0.031	-10000	0	-10000	0	0
GIT1	0.021	0.004	-10000	0	-10000	0	0
GIT1/beta-PIX/PAK1	0.038	0.014	-10000	0	-10000	0	0
Importin alpha/Importin beta/TPX2	0.082	0.095	0.17	275	-10000	0	275
PPP2R5D	0.02	0.004	-10000	0	-10000	0	0
Aurora A/TPX2	0.05	0.082	0.19	89	-10000	0	89
PAK1	0.02	0.005	-10000	0	-10000	0	0
CKAP5	0.021	0.003	-10000	0	-10000	0	0

Effects of Botulinum toxin

Figure S41. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S41. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.037	0.077	0.16	133	-10000	0	133
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.015	0.076	0.23	15	-0.23	36	51
STXBP1	0.019	0.027	-10000	0	-0.33	3	3
ACh/CHRNA1	0.027	0.068	0.25	33	-0.19	9	42
RAB3GAP2/RIMS1/UNC13B	0.025	0.067	0.22	13	-0.2	33	46
mol:Ca2+	0	0	-10000	0	-10000	0	0
UniProt:P30996	0	0	-10000	0	-10000	0	0
UniProt:Q60393	0	0	-10000	0	-10000	0	0
CST086	0	0	-10000	0	-10000	0	0
RIMS1	0.006	0.1	0.32	17	-0.33	35	52
mol:ACh	0.004	0.03	0.08	30	-0.11	10	40
RAB3GAP2	0.019	0.006	-10000	0	-10000	0	0
STX1A/SNAP25/VAMP2	0.026	0.068	0.22	3	-0.16	28	31
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	0.027	0.068	0.25	33	-0.19	9	42
UNC13B	0.019	0.016	-10000	0	-0.33	1	1
CHRNA1	0.034	0.089	0.32	33	-0.33	9	42
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	0.031	0.072	0.25	39	-0.15	10	49
SNAP25	0.004	0.032	0.12	20	-0.22	5	25
VAMP2	0.002	0.001	-10000	0	-10000	0	0
SYT1	0.039	0.091	0.32	39	-0.33	7	46
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.045	0.055	0.13	131	-0.19	3	134
STX1A/SNAP25 fragment 1/VAMP2	0.026	0.068	0.22	3	-0.16	28	31

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.021	0.092	0.18	2	-0.23	64	66
FZD6	0.018	0.017	-10000	0	-0.33	1	1
WNT6	0.04	0.073	0.32	32	-10000	0	32
WNT4	0.009	0.078	0.32	6	-0.33	22	28
FZD3	0.018	0.016	0.32	1	-10000	0	1
WNT5A	0.016	0.037	-10000	0	-0.33	6	6
WNT11	-0.02	0.11	0.32	1	-0.33	61	62

HIF-2-alpha transcription factor network

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
MMP14	0.022	0.064	0.42	2	-0.55	4	6
oxygen homeostasis	0.009	0.014	-10000	0	-10000	0	0
TCEB2	0.021	0.003	-10000	0	-10000	0	0
TCEB1	0.019	0.006	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	0.07	0.098	0.28	13	-0.28	6	19
EPO	0.097	0.15	0.43	37	-0.47	1	38
FIH (dimer)	0.025	0.021	-10000	0	-10000	0	0
APEX1	0.028	0.026	-10000	0	-10000	0	0
SERPINE1	0.11	0.16	0.43	46	-0.51	1	47
FLT1	-0.006	0.12	-10000	0	-0.55	19	19
ADORA2A	0.094	0.15	0.39	50	-0.49	1	51
germ cell development	0.11	0.17	0.42	53	-0.4	4	57
SLC11A2	0.11	0.16	0.4	59	-0.51	1	60
BHLHE40	0.11	0.16	0.42	48	-0.51	1	49
HIF1AN	0.025	0.021	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	0.081	0.12	0.34	33	-0.33	2	35
ETS1	0.019	0.025	-10000	0	-0.36	1	1
CITED2	-0.02	0.15	-10000	0	-0.54	33	33
KDR	-0.008	0.16	-10000	0	-0.78	19	19
PGK1	0.11	0.16	0.41	50	-0.51	1	51
SIRT1	0.021	0.003	-10000	0	-10000	0	0
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	0.13	0.19	0.54	44	-0.57	1	45
EPAS1	0.051	0.097	0.26	42	-0.26	7	49
SP1	0.023	0.01	-10000	0	-10000	0	0
ABCG2	0.096	0.18	0.42	48	-0.44	10	58
EFNA1	0.091	0.15	0.42	35	-0.51	1	36
FXN	0.096	0.15	0.39	50	-0.49	1	51
POU5F1	0.11	0.17	0.43	53	-0.42	4	57
neuron apoptosis	-0.13	0.19	0.55	1	-0.53	44	45
EP300	0.02	0.005	-10000	0	-10000	0	0
EGLN3	0.089	0.13	0.34	110	-0.32	1	111
EGLN2	0.026	0.022	-10000	0	-10000	0	0
EGLN1	0.024	0.021	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.037	0.016	-10000	0	-10000	0	0
VHL	0.02	0.005	-10000	0	-10000	0	0
ARNT	0.024	0.025	-10000	0	-10000	0	0
SLC2A1	0.14	0.18	0.42	108	-0.49	1	109
TWIST1	0.11	0.17	0.43	75	-10000	0	75
ELK1	0.021	0.009	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.088	0.12	0.35	31	-0.34	2	33
VEGFA	0.1	0.16	0.42	46	-0.51	1	47
CREBBP	0.021	0.004	-10000	0	-10000	0	0

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.007	0.003	-10000	0	-10000	0	0
GNB1/GNG2	0.009	0.074	0.21	1	-0.18	67	68
regulation of S phase of mitotic cell cycle	-0.017	0.076	0.16	1	-0.2	67	68
GNAO1	0.021	0.035	0.32	4	-0.33	2	6
HRAS	0.019	0.009	-10000	0	-10000	0	0
SHBG/T-DHT	0.013	0.004	-10000	0	-10000	0	0
PELP1	0.018	0.009	-10000	0	-10000	0	0
AKT1	-0.008	0.002	-10000	0	-10000	0	0
MAP2K1	-0.039	0.063	0.15	15	-0.26	11	26
T-DHT/AR	-0.017	0.082	0.21	1	-0.22	69	70
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-0.006	27	27
GNAI2	0.02	0.004	-10000	0	-10000	0	0
GNAI3	0.02	0.004	-10000	0	-10000	0	0
GNAI1	0.02	0.016	-10000	0	-0.33	1	1
mol:GDP	-0.051	0.11	0.19	2	-0.31	72	74
cell proliferation	-0.056	0.12	0.23	1	-0.42	36	37
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
FOS	-0.054	0.17	-10000	0	-0.68	32	32
mol:Ca2+	-0.008	0.019	0.051	1	-0.056	48	49
MAPK3	-0.049	0.093	0.24	2	-0.33	32	34
MAPK1	-0.033	0.1	-10000	0	-0.39	29	29
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
mol:IP3	0	0.001	-10000	0	-0.004	25	25
cAMP biosynthetic process	0.001	0.018	0.23	1	-10000	0	1
GNG2	0.019	0.022	-10000	0	-0.33	2	2
potassium channel inhibitor activity	0	0.001	-10000	0	-0.004	25	25
HRAS/GTP	0.007	0.07	-10000	0	-0.16	66	66
actin cytoskeleton reorganization	0.026	0.016	-10000	0	-0.16	1	1
SRC	0.019	0.008	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.004	25	25
PI3K	0.026	0.012	-10000	0	-0.19	1	1
apoptosis	0.041	0.12	0.44	32	-10000	0	32
T-DHT/AR/PELP1	-0.004	0.075	0.2	1	-0.19	69	70
HRAS/GDP	-0.052	0.1	0.18	2	-0.3	69	71
CREB1	-0.044	0.12	-10000	0	-0.48	32	32
RAC1-CDC42/GTP	0.033	0.019	-10000	0	-0.16	1	1
AR	-0.027	0.12	0.32	1	-0.33	69	70
GNB1	0.021	0.004	-10000	0	-10000	0	0
RAF1	-0.034	0.063	0.16	16	-0.24	11	27
RAC1-CDC42/GDP	-0.02	0.11	0.2	1	-0.3	62	63
T-DHT/AR/PELP1/Src	0.007	0.073	0.2	1	-0.18	67	68
MAP2K2	-0.039	0.061	0.15	13	-0.26	11	24
T-DHT/AR/PELP1/Src/PI3K	-0.017	0.076	0.16	1	-0.21	67	68
GNAZ	-0.006	0.092	-10000	0	-0.33	39	39
SHBG	0.019	0.006	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.023	0.097	-10000	0	-0.36	25	25
mol:T-DHT	0	0	-10000	0	-0.003	6	6
RAC1	0.019	0.007	-10000	0	-10000	0	0
GNRH1	-0.008	0.017	-10000	0	-0.22	3	3
Gi family/GTP	-0.025	0.068	0.15	1	-0.2	48	49
CDC42	0.021	0.003	-10000	0	-10000	0	0

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	0.008	0.064	-10000	0	-0.33	18	18
GNB1/GNG2	-0.004	0.1	0.23	1	-0.3	22	23
mol:DAG	-0.034	0.081	0.19	3	-0.28	20	23
PLCG1	-0.034	0.083	0.19	3	-0.29	20	23
YES1	-0.027	0.086	0.22	5	-0.23	60	65
FZD3	0.018	0.016	0.32	1	-10000	0	1
FZD6	0.018	0.017	-10000	0	-0.33	1	1
G protein	-0.003	0.1	0.25	3	-0.29	21	24
MAP3K7	-0.039	0.086	0.2	4	-0.27	33	37
mol:Ca2+	-0.033	0.079	0.18	3	-0.27	20	23
mol:IP3	-0.034	0.081	0.19	3	-0.28	20	23
NLK	0	0.079	-10000	0	-0.79	5	5
GNB1	0.021	0.004	-10000	0	-10000	0	0
CAMK2A	-0.042	0.093	0.22	3	-0.28	37	40
MAP3K7IP1	0	0	-10000	0	-10000	0	0
Noncanonical Wnts/FZD	-0.021	0.092	0.18	2	-0.23	64	66
CSNK1A1	0.02	0.005	-10000	0	-10000	0	0
GNAS	-0.028	0.083	0.16	2	-0.22	60	62
GO:0007205	-0.031	0.08	0.18	3	-0.28	21	24
WNT6	0.04	0.073	0.32	32	-10000	0	32
WNT4	0.009	0.078	0.32	6	-0.33	22	28
NFAT1/CK1 alpha	-0.012	0.1	0.27	5	-0.3	21	26
GNG2	0.019	0.022	-10000	0	-0.33	2	2
WNT5A	0.016	0.037	-10000	0	-0.33	6	6
WNT11	-0.02	0.11	0.32	1	-0.33	61	62
CDC42	-0.029	0.085	0.21	6	-0.3	21	27

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	-0.07	0.15	-10000	0	-0.33	133	133
oxygen homeostasis	0	0	-10000	0	-10000	0	0
TCEB2	0.021	0.003	-10000	0	-10000	0	0
TCEB1	0.019	0.006	-10000	0	-10000	0	0
HIF1A/p53	0.029	0.053	0.22	3	-0.24	8	11
HIF1A	0.001	0.035	-10000	0	-0.25	8	8
COPS5	0.019	0.006	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.051	0.027	-10000	0	-10000	0	0
FIH (dimer)	0.021	0.003	-10000	0	-10000	0	0
CDKN2A	0.096	0.14	0.32	135	-10000	0	135
ARNT/IPAS	-0.032	0.11	-10000	0	-0.23	113	113
HIF1AN	0.021	0.003	-10000	0	-10000	0	0
GNB2L1	0.02	0.004	-10000	0	-10000	0	0
HIF1A/ARNT	0.022	0.043	0.21	2	-0.23	5	7
CUL2	0.02	0.004	-10000	0	-10000	0	0
OS9	0.02	0.005	-10000	0	-10000	0	0
RACK1/Elongin B/Elongin C	0.037	0.016	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF1A/Hsp90	0.029	0.051	0.18	1	-0.24	8	9
PHD1-3/OS9	0.078	0.079	0.23	94	-10000	0	94
HIF1A/RACK1/Elongin B/Elongin C	0.041	0.05	0.24	2	-0.24	6	8
VHL	0.02	0.005	-10000	0	-10000	0	0
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
HIF1A/JAB1	0.026	0.052	0.24	2	-0.24	8	10
EGLN3	0.083	0.13	0.32	110	-0.33	1	111
EGLN2	0.02	0.004	-10000	0	-10000	0	0
EGLN1	0.02	0.006	-10000	0	-10000	0	0
TP53	0.02	0.006	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.008	0.1	-10000	0	-0.5	19	19
ARNT	0.017	0.008	-10000	0	-10000	0	0
ARD1A	0	0	-10000	0	-10000	0	0
RBX1	0.02	0.004	-10000	0	-10000	0	0
HIF1A/p19ARF	0.069	0.098	0.22	131	-0.22	6	137

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.047	0.1	-10000	0	-0.29	31	31
epithelial cell differentiation	-0.028	0.09	-10000	0	-0.3	6	6
ITCH	0.031	0.018	-10000	0	-10000	0	0
WWP1	-0.017	0.07	-10000	0	-10000	0	0
FYN	0.019	0.016	-10000	0	-0.33	1	1
EGFR	0.014	0.045	0.32	1	-0.33	8	9
PRL	0.025	0.044	0.32	11	-10000	0	11
neuron projection morphogenesis	-0.03	0.094	0.38	5	-10000	0	5
PTPRZ1	0.03	0.15	0.32	65	-0.33	42	107
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.019	0.082	-10000	0	-10000	0	0
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.042	0.083	-10000	0	-0.26	32	32
ADAM17	0.033	0.019	-10000	0	-10000	0	0
ErbB4/ErbB4	-0.032	0.066	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.086	0.12	-10000	0	-0.29	76	76
NCOR1	0.02	0.006	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.038	0.084	-10000	0	-0.25	33	33
GRIN2B	-0.047	0.078	0.26	3	-0.24	27	30
ErbB4/ErbB2/betacellulin	-0.011	0.065	-10000	0	-0.25	6	6
STAT1	0.021	0.002	-10000	0	-10000	0	0
HBEGF	-0.032	0.12	-10000	0	-0.33	78	78
PRLR	0.021	0.095	0.32	26	-0.33	18	44
E4ICDs/ETO2	-0.029	0.086	-10000	0	-0.29	14	14
axon guidance	-0.027	0.069	-10000	0	-0.36	4	4
NEDD4	0.03	0.023	-10000	0	-0.3	1	1
Prolactin receptor/Prolactin receptor/Prolactin	0.028	0.074	0.24	33	-0.23	18	51
CBFA2T3	0.002	0.076	-10000	0	-0.33	26	26
ErbB4/ErbB2/HBEGF	-0.032	0.085	-10000	0	-0.25	24	24
MAPK3	-0.036	0.08	-10000	0	-10000	0	0
STAT1 (dimer)	-0.023	0.077	-10000	0	-0.3	3	3
MAPK1	-0.035	0.079	0.24	1	-10000	0	1
JAK2	0.018	0.023	-10000	0	-0.33	2	2
ErbB4/ErbB2/neuregulin 1 beta	-0.052	0.075	-10000	0	-0.25	30	30
NRG1	-0.041	0.084	-10000	0	-0.22	85	85
NRG3	-0.11	0.17	0.32	1	-0.33	197	198
NRG2	-0.018	0.11	-10000	0	-0.33	56	56
NRG4	0.036	0.09	0.32	36	-0.33	8	44
heart development	-0.027	0.069	-10000	0	-0.36	4	4
neural crest cell migration	-0.052	0.074	-10000	0	-0.24	30	30
ERBB2	0	0.031	0.3	3	-10000	0	3
WWOX/E4ICDs	-0.02	0.074	-10000	0	-0.3	3	3
SHC1	0.018	0.016	0.32	1	-10000	0	1
ErbB4/EGFR/neuregulin 4	-0.004	0.091	0.29	1	-0.28	11	12
apoptosis	0.15	0.2	0.39	176	-10000	0	176
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.04	0.097	-10000	0	-0.29	26	26
ErbB4/ErbB2/epiregulin	-0.002	0.11	0.32	4	-0.25	21	25
ErbB4/ErbB4/betacellulin/betacellulin	-0.024	0.083	-10000	0	-0.3	10	10
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.014	0.11	0.3	2	-0.27	24	26
MDM2	-0.023	0.073	0.24	17	-10000	0	17
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.033	0.077	-10000	0	-0.22	31	31
STAT5A	-0.029	0.072	-10000	0	-0.38	4	4
ErbB4/EGFR/neuregulin 1 beta	-0.034	0.083	-10000	0	-0.26	27	27
DLG4	0.02	0.006	-10000	0	-10000	0	0
GRB2/SHC	0.026	0.012	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.02	0.069	-10000	0	-0.28	3	3
STAT5A (dimer)	-0.025	0.099	0.28	1	-0.35	3	4
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.02	0.082	-10000	0	-0.37	5	5
LRIG1	0.019	0.022	-10000	0	-0.33	2	2
EREG	0.011	0.18	0.32	78	-0.33	82	160
BTC	0.013	0.054	0.32	1	-0.33	12	13
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.027	0.066	-10000	0	-0.36	3	3
ERBB4	-0.032	0.066	-10000	0	-10000	0	0
STAT5B	0.021	0.003	-10000	0	-10000	0	0
YAP1	-0.006	0.069	-10000	0	-0.44	11	11
GRB2	0.02	0.004	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0.003	0.078	-10000	0	-0.24	7	7
glial cell differentiation	0.02	0.069	0.27	3	-10000	0	3
WWOX	0.02	0.006	-10000	0	-10000	0	0
cell proliferation	-0.061	0.11	0.32	3	-0.37	19	22

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.016	0.002	-10000	0	-10000	0	0
PRKCZ	0.019	0.027	-10000	0	-0.33	3	3
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.02	0.005	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.003	0.061	-10000	0	-0.26	17	17
IRAK/TOLLIP	0.019	0.009	0.18	1	-10000	0	1
IKBKB	0.018	0.007	-10000	0	-10000	0	0
IKBKG	0.02	0.004	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.038	0.13	0.24	22	-0.23	153	175
IL1A	-0.081	0.16	0.32	3	-0.33	153	156
IL1B	-0.031	0.055	-10000	0	-0.23	36	36
IRAK/TRAF6/p62/Atypical PKCs	0.042	0.028	-10000	0	-0.17	3	3
IL1R2	0.032	0.067	0.32	22	-0.33	3	25
IL1R1	0.02	0.022	-10000	0	-0.33	2	2
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.007	0.05	-10000	0	-0.26	10	10
TOLLIP	0.021	0.004	-10000	0	-10000	0	0
TICAM2	0.018	0.031	-10000	0	-0.33	4	4
MAP3K3	0.02	0.016	-10000	0	-0.33	1	1
TAK1/TAB1/TAB2	0.013	0.004	-10000	0	-10000	0	0
IKK complex/ELKS	0.001	0.057	-10000	0	-0.36	2	2
JUN	-0.02	0.028	0.14	8	-0.16	2	10
MAP3K7	0.019	0.006	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.031	0.059	-10000	0	-0.17	33	33
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.017	0.11	0.23	2	-0.18	152	154
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.009	0.11	-10000	0	-0.17	150	150
IL1 beta fragment/IL1R1/IL1RAP	0.014	0.055	-10000	0	-0.18	36	36
NFKB1	0.021	0.003	-10000	0	-10000	0	0
MAPK8	-0.015	0.031	0.16	9	-0.16	2	11
IRAK1	-0.012	0.01	0.2	1	-10000	0	1
IL1RN/IL1R1	0.026	0.036	-10000	0	-0.23	10	10
IRAK4	0.021	0.003	-10000	0	-10000	0	0
PRKCI	0.02	0.005	-10000	0	-10000	0	0
TRAF6	0.021	0.003	-10000	0	-10000	0	0
PI3K	0.029	0.014	-10000	0	-0.23	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.005	0.061	-10000	0	-0.3	11	11
CHUK	0.021	0.003	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.014	0.055	-10000	0	-0.18	36	36
IL1 beta/IL1R2	0.015	0.071	0.22	19	-0.2	36	55
IRAK/TRAF6/TAK1/TAB1/TAB2	0.024	0.01	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.022	0.055	-10000	0	-0.17	26	26
IRAK3	0.012	0.055	-10000	0	-0.33	13	13
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.03	0.06	-10000	0	-0.18	29	29
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.048	0.1	-10000	0	-0.2	144	144
IL1 alpha/IL1R1/IL1RAP	-0.028	0.11	0.22	3	-0.2	152	155
RELA	0.021	0.004	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.02	0.005	-10000	0	-10000	0	0
MYD88	0.021	0.004	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0.031	0.015	0.18	1	-10000	0	1
IL1RAP	0.02	0.005	-10000	0	-10000	0	0
UBE2N	0.021	0.003	-10000	0	-10000	0	0
IRAK/TRAF6	-0.044	0.034	-10000	0	-0.28	1	1
CASP1	0.016	0.038	-10000	0	-0.33	6	6
IL1RN/IL1R2	0.035	0.058	0.23	22	-0.25	10	32
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.024	0.057	-10000	0	-0.17	36	36
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.042	0.098	-10000	0	-0.33	24	24
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
IL1RN	0.016	0.043	-10000	0	-0.33	8	8
TRAF6/TAK1/TAB1/TAB2	0.028	0.01	-10000	0	-10000	0	0
MAP2K6	-0.008	0.042	0.17	24	-0.16	2	26

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.019	0.096	-10000	0	-0.58	8	8
Syndecan-4/Syndesmos	0.037	0.16	0.3	5	-0.72	14	19
positive regulation of JNK cascade	0.035	0.15	0.29	4	-0.66	14	18
Syndecan-4/ADAM12	0.096	0.19	0.33	94	-0.72	14	108
CCL5	0.017	0.034	-10000	0	-0.33	5	5
Rac1/GDP	0.014	0.005	-10000	0	-10000	0	0
DNM2	0.02	0.005	-10000	0	-10000	0	0
ITGA5	0.021	0.021	0.32	1	-0.33	1	2
SDCBP	0.019	0.006	-10000	0	-10000	0	0
PLG	0.012	0.05	0.32	11	-10000	0	11
ADAM12	0.12	0.14	0.32	171	-10000	0	171
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0.021	0.003	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.035	0.019	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	0.04	0.16	0.32	7	-0.7	14	21
Syndecan-4/CXCL12/CXCR4	0.037	0.16	0.3	4	-0.71	14	18
Syndecan-4/Laminin alpha3	0.019	0.15	0.3	2	-0.69	16	18
MDK	0.11	0.14	0.32	151	-10000	0	151
Syndecan-4/FZD7	0.037	0.15	0.3	5	-0.72	14	19
Syndecan-4/Midkine	0.09	0.18	0.34	57	-0.71	14	71
FZD7	0.02	0.016	-10000	0	-0.33	1	1
Syndecan-4/FGFR1/FGF	0.022	0.16	0.31	1	-0.63	18	19
THBS1	0.019	0.022	-10000	0	-0.33	2	2
integrin-mediated signaling pathway	0.045	0.16	0.31	13	-0.67	15	28
positive regulation of MAPKKK cascade	0.035	0.15	0.29	4	-0.66	14	18
Syndecan-4/TACI	0.049	0.17	0.32	28	-0.71	14	42
CXCR4	0.021	0.002	-10000	0	-10000	0	0
cell adhesion	0.008	0.039	0.19	11	-0.27	4	15
Syndecan-4/Dynamin	0.037	0.15	0.3	4	-0.71	14	18
Syndecan-4/TSP1	0.036	0.15	0.3	5	-0.67	16	21
Syndecan-4/GIPC	0.038	0.15	0.3	5	-0.71	14	19
Syndecan-4/RANTES	0.038	0.16	0.3	5	-0.7	15	20
ITGB1	0.021	0.004	-10000	0	-10000	0	0
LAMA1	0.024	0.066	0.32	15	-0.33	7	22
LAMA3	-0.042	0.13	0.32	1	-0.33	91	92
RAC1	0.019	0.007	-10000	0	-10000	0	0
PRKCA	0.005	0.15	0.78	18	-0.32	1	19
Syndecan-4/alpha-Actinin	0.036	0.15	0.3	4	-0.69	15	19
TFPI	0.006	0.07	-10000	0	-0.33	22	22
F2	0.063	0.11	0.33	72	-10000	0	72
alpha5/beta1 Integrin	0.03	0.016	0.23	1	-0.23	1	2
positive regulation of cell adhesion	0.003	0.15	0.3	2	-0.64	17	19
ACTN1	0.021	0.004	-10000	0	-10000	0	0
TNC	0.032	0.081	0.32	28	-0.33	7	35
Syndecan-4/CXCL12	0.033	0.16	0.3	5	-0.71	15	20
FGF6	0.017	0.004	-10000	0	-10000	0	0
RHOA	0.02	0.004	-10000	0	-10000	0	0
CXCL12	0	0.083	-10000	0	-0.33	31	31
TNFRSF13B	0.041	0.09	0.32	41	-0.33	5	46
FGF2	-0.027	0.12	-10000	0	-0.33	70	70
FGFR1	0.018	0.017	-10000	0	-0.33	1	1
Syndecan-4/PI-4-5-P2	0.022	0.15	0.28	6	-0.69	15	21
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.014	0.038	0.32	1	-0.32	4	5
cell migration	-0.021	0.013	-10000	0	-10000	0	0
PRKCD	0.016	0.018	-10000	0	-10000	0	0
vasculogenesis	0.036	0.15	0.3	5	-0.64	16	21
SDC4	0.033	0.15	0.3	6	-0.85	10	16
Syndecan-4/Tenascin C	0.045	0.16	0.32	12	-0.7	15	27
Syndecan-4/PI-4-5-P2/PKC alpha	-0.028	0.015	-10000	0	-10000	0	0
Syndecan-4/Syntenin	0.034	0.15	0.3	5	-0.71	14	19
MMP9	0.085	0.13	0.32	109	-10000	0	109
Rac1/GTP	0.008	0.039	0.19	11	-0.28	4	15
cytoskeleton organization	0.037	0.15	0.3	5	-0.68	14	19
GIPC1	0.02	0.005	-10000	0	-10000	0	0
Syndecan-4/TFPI	0.033	0.16	0.3	4	-0.68	16	20

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.015	0.034	-10000	0	-0.32	4	4
PDGF/PDGFRA/CRKL	0.025	0.026	-10000	0	-0.21	4	4
positive regulation of JUN kinase activity	0.038	0.028	-10000	0	-0.17	1	1
CRKL	0.02	0.005	-10000	0	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.028	0.1	-10000	0	-0.23	104	104
AP1	-0.054	0.17	0.27	1	-0.73	27	28
mol:IP3	-0.019	0.023	-10000	0	-0.22	3	3
PLCG1	-0.019	0.023	-10000	0	-0.22	3	3
PDGF/PDGFRA/alphaV Integrin	0.025	0.027	-10000	0	-0.21	4	4
RAPGEF1	0.021	0.004	-10000	0	-10000	0	0
CRK	0.019	0.006	-10000	0	-10000	0	0
mol:Ca2+	-0.019	0.023	-10000	0	-0.22	3	3
CAV3	-0.05	0.14	-10000	0	-0.33	101	101
CAV1	-0.19	0.17	-10000	0	-0.33	311	311
SHC/Grb2/SOS1	0.04	0.029	-10000	0	-0.18	1	1
PDGF/PDGFRA/Shf	0.026	0.029	0.24	2	-0.21	4	6
FOS	-0.055	0.16	0.31	2	-0.73	26	28
JUN	-0.023	0.023	-10000	0	-0.23	3	3
oligodendrocyte development	0.025	0.027	-10000	0	-0.21	4	4
GRB2	0.02	0.004	-10000	0	-10000	0	0
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
mol:DAG	-0.019	0.023	-10000	0	-0.22	3	3
PDGF/PDGFRA	0.015	0.034	-10000	0	-0.31	4	4
actin cytoskeleton reorganization	0.024	0.026	-10000	0	-0.21	4	4
SRF	-0.014	0.011	-10000	0	-10000	0	0
SHC1	0.018	0.016	0.32	1	-10000	0	1
PI3K	0.033	0.029	-10000	0	-0.18	5	5
PDGF/PDGFRA/Crk/C3G	0.033	0.028	-10000	0	-0.18	4	4
JAK1	-0.017	0.018	-10000	0	-0.21	3	3
ELK1/SRF	-0.021	0.035	0.15	17	-0.19	2	19
SHB	0.02	0.006	-10000	0	-10000	0	0
SHF	0.021	0.019	0.32	2	-10000	0	2
CSNK2A1	0.022	0.015	-10000	0	-10000	0	0
GO:0007205	-0.015	0.024	-10000	0	-0.25	3	3
SOS1	0.021	0.003	-10000	0	-10000	0	0
Ras protein signal transduction	0.038	0.028	-10000	0	-0.17	1	1
PDGF/PDGFRA/SHB	0.024	0.026	-10000	0	-0.21	4	4
PDGF/PDGFRA/Caveolin-1	-0.13	0.13	-10000	0	-0.24	304	304
ITGAV	0.021	0.002	-10000	0	-10000	0	0
ELK1	-0.019	0.025	-10000	0	-0.23	2	2
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
PDGF/PDGFRA/Crk	0.023	0.027	-10000	0	-0.21	4	4
JAK-STAT cascade	-0.017	0.018	-10000	0	-0.21	3	3
cell proliferation	0.026	0.029	0.23	2	-0.21	4	6

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	-0.016	0.005	-10000	0	-10000	0	0
SMARCC1	0.002	0.013	-10000	0	-10000	0	0
REL	0.02	0.007	-10000	0	-10000	0	0
HDAC7	-0.035	0.076	0.29	6	-0.27	20	26
JUN	0.019	0.027	-10000	0	-0.33	3	3
EP300	0.02	0.005	-10000	0	-10000	0	0
KAT2B	0.02	0.004	-10000	0	-10000	0	0
KAT5	0.021	0.004	-10000	0	-10000	0	0
MAPK14	-0.012	0.034	0.15	15	-0.24	2	17
FOXO1	0.02	0.005	-10000	0	-10000	0	0
T-DHT/AR	-0.032	0.079	0.31	2	-0.28	19	21
MAP2K6	0.024	0.058	0.32	15	-0.34	2	17
BRM/BAF57	0.026	0.023	-10000	0	-0.23	3	3
MAP2K4	0.016	0.015	-10000	0	-10000	0	0
SMARCA2	0.017	0.027	-10000	0	-0.33	3	3
PDE9A	-0.031	0.16	-10000	0	-0.8	16	16
NCOA2	0.016	0.035	-10000	0	-0.33	5	5
CEBPA	0.004	0.072	-10000	0	-0.33	23	23
EHMT2	0.021	0.004	-10000	0	-10000	0	0
cell proliferation	-0.026	0.14	0.33	18	-0.39	25	43
NR0B1	0.08	0.12	0.32	104	-10000	0	104
EGR1	0.004	0.073	-10000	0	-0.33	24	24
RXRs/9cRA	-0.064	0.1	-10000	0	-0.18	236	236
AR/RACK1/Src	-0.013	0.079	0.26	17	-0.29	2	19
AR/GR	-0.014	0.085	0.22	3	-0.22	55	58
GNB2L1	0.021	0.005	-10000	0	-10000	0	0
PKN1	0.02	0.005	-10000	0	-10000	0	0
RCHY1	0.021	0.003	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0.002	-10000	0	-10000	0	0
MAPK8	-0.014	0.014	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.017	0.069	0.27	4	-0.28	3	7
SRC	-0.022	0.03	0.19	3	-0.2	2	5
NR3C1	0.021	0.004	-10000	0	-10000	0	0
KLK3	0.014	0.09	-10000	0	-10000	0	0
APPBP2	0.016	0.015	-10000	0	-10000	0	0
TRIM24	0.02	0.005	-10000	0	-10000	0	0
T-DHT/AR/TIP60	-0.02	0.065	0.24	9	-0.3	2	11
TMPRSS2	-0.079	0.27	-10000	0	-0.9	46	46
RXRG	-0.14	0.17	-10000	0	-0.33	238	238
mol:9cRA	0	0	-10000	0	-10000	0	0
RXRA	0.021	0.004	-10000	0	-10000	0	0
RXRB	0.021	0.004	-10000	0	-10000	0	0
CARM1	0.021	0.006	-10000	0	-10000	0	0
NR2C2	0.021	0.004	-10000	0	-10000	0	0
KLK2	-0.003	0.084	0.29	26	-10000	0	26
AR	-0.029	0.076	0.19	2	-0.24	55	57
SENP1	0.021	0.003	-10000	0	-10000	0	0
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
MDM2	0.019	0.009	-10000	0	-10000	0	0
SRY	0	0.003	-10000	0	-0.027	7	7
GATA2	-0.006	0.093	-10000	0	-0.33	40	40
MYST2	0	0.001	-10000	0	-10000	0	0
HOXB13	0.12	0.14	0.32	174	-10000	0	174
T-DHT/AR/RACK1/Src	-0.018	0.072	0.29	10	-0.3	2	12
positive regulation of transcription	-0.006	0.093	-10000	0	-0.32	40	40
DNAJA1	0.016	0.016	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.007	0.011	0.17	2	-10000	0	2
NCOA1	0.023	0.015	-10000	0	-10000	0	0
SPDEF	0.11	0.14	0.32	159	-0.33	3	162
T-DHT/AR/TIF2	-0.009	0.075	0.23	7	-0.35	9	16
T-DHT/AR/Hsp90	-0.021	0.061	0.24	7	-0.27	3	10
GSK3B	0.018	0.012	-10000	0	-10000	0	0
NR2C1	0.02	0.006	-10000	0	-10000	0	0
mol:T-DHT	-0.021	0.027	0.11	1	-0.21	2	3
SIRT1	0.021	0.003	-10000	0	-10000	0	0
ZMIZ2	0.018	0.01	-10000	0	-10000	0	0
POU2F1	0.01	0.038	-10000	0	-0.17	4	4
T-DHT/AR/DAX-1	0.019	0.11	0.22	82	-0.31	2	84
CREBBP	0.021	0.004	-10000	0	-10000	0	0
SMARCE1	0.021	0.004	-10000	0	-10000	0	0

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.013	0.031	0.22	1	-0.21	8	9
EPHB2	0.053	0.094	0.32	55	-10000	0	55
Syndecan-2/TACI	0.028	0.064	0.22	41	-0.19	9	50
LAMA1	0.024	0.066	0.32	15	-0.33	7	22
Syndecan-2/alpha2 ITGB1	0.007	0.081	0.23	11	-0.17	71	82
HRAS	0.021	0.004	-10000	0	-10000	0	0
Syndecan-2/CASK	-0.007	0.018	-10000	0	-0.18	5	5
ITGA5	0.021	0.021	0.32	1	-0.33	1	2
BAX	-0.013	0.013	-10000	0	-10000	0	0
EPB41	0.021	0.003	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	0.013	0.019	-10000	0	-0.17	5	5
LAMA3	-0.042	0.13	0.32	1	-0.33	91	92
EZR	0.019	0.006	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	-0.049	0.14	-10000	0	-0.33	102	102
Syndecan-2/MMP2	0.014	0.023	0.22	1	-0.18	5	6
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.033	0.037	0.23	13	-0.23	2	15
dendrite morphogenesis	0.037	0.071	0.23	55	-0.19	5	60
Syndecan-2/GM-CSF	0.007	0.059	0.23	9	-0.19	30	39
determination of left/right symmetry	-0.008	0.021	-10000	0	-0.22	5	5
Syndecan-2/PKC delta	0.014	0.021	-10000	0	-0.19	5	5
GNB2L1	0.02	0.004	-10000	0	-10000	0	0
MAPK3	-0.005	0.072	0.18	46	-0.18	29	75
MAPK1	-0.003	0.071	0.18	46	-0.18	24	70
Syndecan-2/RACK1	0.024	0.019	-10000	0	-0.15	4	4
NF1	0.021	0.004	-10000	0	-10000	0	0
FGFR/FGF/Syndecan-2	-0.008	0.021	-10000	0	-0.22	5	5
ITGA2	0.026	0.053	0.32	13	-0.33	2	15
MAPK8	-0.011	0.016	-10000	0	-0.19	4	4
Syndecan-2/alpha2/beta1 Integrin	0.041	0.059	0.25	24	-0.19	7	31
Syndecan-2/Kininogen	0.027	0.057	0.22	35	-0.18	5	40
ITGB1	0.021	0.004	-10000	0	-10000	0	0
SRC	0.003	0.061	0.17	57	-10000	0	57
Syndecan-2/CASK/Protein 4.1	0.013	0.019	-10000	0	-0.17	5	5
extracellular matrix organization	0.014	0.021	-10000	0	-0.19	5	5
actin cytoskeleton reorganization	0.013	0.031	0.22	1	-0.21	8	9
Syndecan-2/Caveolin-2/Ras	-0.008	0.075	-10000	0	-0.17	85	85
Syndecan-2/Laminin alpha3	-0.017	0.075	0.22	1	-0.19	80	81
Syndecan-2/RasGAP	0.031	0.022	-10000	0	-0.16	3	3
alpha5/beta1 Integrin	0.03	0.016	0.23	1	-0.23	1	2
PRKCD	0.02	0.004	-10000	0	-10000	0	0
Syndecan-2 dimer	0.037	0.071	0.23	55	-0.19	5	60
GO:0007205	0.001	0	-10000	0	-10000	0	0
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	-0.018	0.024	0.16	6	-10000	0	6
RHOA	0.02	0.004	-10000	0	-10000	0	0
SDCBP	0.019	0.006	-10000	0	-10000	0	0
TNFRSF13B	0.041	0.09	0.32	41	-0.33	5	46
RASA1	0.02	0.005	-10000	0	-10000	0	0
alpha2/beta1 Integrin	0.033	0.037	0.23	13	-0.23	2	15
Syndecan-2/Synbindin	0.014	0.019	-10000	0	-0.18	4	4
TGFB1	0.021	0.004	-10000	0	-10000	0	0
CASP3	0.003	0.062	0.18	51	-0.17	5	56
FN1	0.019	0.033	0.32	1	-0.33	4	5
Syndecan-2/IL8	0.021	0.045	0.23	17	-0.18	6	23
SDC2	-0.008	0.021	-10000	0	-0.22	5	5
KNG1	0.039	0.077	0.32	35	-10000	0	35
Syndecan-2/Neurofibromin	0.015	0.019	-10000	0	-0.18	4	4
TRAPPC4	0.02	0.004	-10000	0	-10000	0	0
CSF2	0.003	0.095	0.32	9	-0.33	33	42
Syndecan-2/TGFB1	0.014	0.021	-10000	0	-0.19	5	5
Syndecan-2/Syntenin/PI-4-5-P2	0.013	0.019	-10000	0	-0.17	5	5
Syndecan-2/Ezrin	0.023	0.023	-10000	0	-0.17	5	5
PRKACA	0.005	0.061	0.18	53	-0.17	2	55
angiogenesis	0.021	0.045	0.23	17	-0.18	6	23
MMP2	0.021	0.014	0.32	1	-10000	0	1
IL8	0.029	0.059	0.32	17	-0.33	2	19
calcineurin-NFAT signaling pathway	0.028	0.064	0.22	41	-0.19	9	50

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.02	0.004	-10000	0	-10000	0	0
alphaV beta3 Integrin	0.037	0.05	0.23	23	-0.23	5	28
PTK2	-0.022	0.11	-10000	0	-0.35	31	31
positive regulation of JNK cascade	-0.022	0.11	-10000	0	-0.29	45	45
CDC42/GDP	-0.022	0.15	-10000	0	-0.38	48	48
Rac1/GDP	-0.023	0.14	-10000	0	-0.38	46	46
RAP1B	0.02	0.005	-10000	0	-10000	0	0
RAP1A	0.02	0.004	-10000	0	-10000	0	0
CTNNB1	0.021	0.004	-10000	0	-10000	0	0
CDC42/GTP	-0.022	0.14	-10000	0	-0.35	42	42
nectin-3/I-afadin	0.009	0.068	-10000	0	-0.23	39	39
RAPGEF1	-0.039	0.14	0.28	1	-0.38	55	56
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.045	0.15	-10000	0	-0.42	59	59
PDGFB-D/PDGFRB	0.02	0.004	-10000	0	-10000	0	0
TLN1	-0.025	0.055	-10000	0	-0.33	11	11
Rap1/GTP	-0.027	0.11	-10000	0	-0.29	54	54
IQGAP1	0.021	0.003	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.034	0.016	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.009	0.068	-10000	0	-0.23	39	39
PVR	0.02	0.005	-10000	0	-10000	0	0
Necl-5(dimer)	0.02	0.005	-10000	0	-10000	0	0
mol:GDP	-0.039	0.17	-10000	0	-0.46	49	49
MLLT4	0.019	0.006	-10000	0	-10000	0	0
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
PI3K	0.037	0.062	-10000	0	-0.18	30	30
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.031	0.031	0.23	10	-10000	0	10
positive regulation of lamellipodium assembly	-0.024	0.12	-10000	0	-0.3	49	49
PVRL1	0.026	0.042	0.32	10	-10000	0	10
PVRL3	-0.005	0.093	0.32	1	-0.33	39	40
PVRL2	0.02	0.004	-10000	0	-10000	0	0
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
CDH1	0.019	0.022	-10000	0	-0.33	2	2
CLDN1	0.023	0.055	0.32	10	-0.33	5	15
JAM-A/CLDN1	0.031	0.068	0.23	10	-0.19	31	41
SRC	-0.047	0.17	-10000	0	-0.44	69	69
ITGB3	0.031	0.072	0.32	23	-0.33	5	28
nectin-1(dimer)/I-afadin/I-afadin	0.031	0.031	0.23	10	-10000	0	10
FARP2	-0.035	0.17	-10000	0	-0.46	41	41
RAC1	0.019	0.007	-10000	0	-10000	0	0
CTNNA1	0.02	0.004	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.021	0.061	-10000	0	-0.19	37	37
nectin-1/I-afadin	0.031	0.031	0.23	10	-10000	0	10
nectin-2/I-afadin	0.028	0.011	-10000	0	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0.025	0.01	-10000	0	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.024	0.065	0.22	8	-0.19	36	44
CDC42/GTP/IQGAP1/filamentous actin	0.028	0.006	-10000	0	-10000	0	0
F11R	0.018	0.017	-10000	0	-0.33	1	1
positive regulation of filopodium formation	-0.022	0.11	-10000	0	-0.29	45	45
alphaV/beta3 Integrin/Talin	-0.025	0.08	0.2	24	-0.3	15	39
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.028	0.011	-10000	0	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.028	0.011	-10000	0	-10000	0	0
PIP5K1C	-0.021	0.06	-10000	0	-0.2	38	38
VAV2	-0.041	0.18	-10000	0	-0.49	47	47
RAP1/GDP	-0.02	0.14	-10000	0	-0.35	45	45
ITGAV	0.021	0.002	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.02	0.062	-10000	0	-0.19	38	38
nectin-3(dimer)/I-afadin/I-afadin	0.009	0.068	-10000	0	-0.23	39	39
Rac1/GTP	-0.026	0.14	-10000	0	-0.37	47	47
PTPRM	-0.014	0.072	-10000	0	-0.22	45	45
E-cadherin/beta catenin/alpha catenin	0.052	0.036	-10000	0	-0.15	1	1
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.021	0.003	-10000	0	-10000	0	0

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.013	0.063	-10000	0	-10000	0	0
PLK1	0.2	0.26	0.56	138	-10000	0	138
CDKN1B	0.13	0.17	0.42	71	-0.35	4	75
FOXO3	0.19	0.23	0.52	136	-10000	0	136
KAT2B	0.054	0.044	0.18	12	-10000	0	12
FOXO1/SIRT1	0.008	0.041	-10000	0	-0.25	2	2
CAT	0.15	0.24	0.56	59	-0.79	6	65
CTNNB1	0.02	0.004	-10000	0	-10000	0	0
AKT1	0.054	0.043	0.17	9	-10000	0	9
FOXO1	0.016	0.056	0.23	12	-0.26	2	14
MAPK10	0.015	0.063	0.2	38	-0.16	14	52
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.033	0.072	0.31	5	-10000	0	5
response to oxidative stress	0.036	0.042	0.13	44	-10000	0	44
FOXO3A/SIRT1	0.16	0.2	0.44	127	-0.42	3	130
XPO1	0.021	0.002	-10000	0	-10000	0	0
EP300	0.022	0.007	-10000	0	-10000	0	0
BCL2L11	0.063	0.061	-10000	0	-10000	0	0
FOXO1/SKP2	0.022	0.042	-10000	0	-10000	0	0
mol:GDP	0.036	0.042	0.13	44	-10000	0	44
RAN	0.022	0.014	0.32	1	-10000	0	1
GADD45A	0.11	0.17	0.45	19	-0.63	8	27
YWHAQ	0.021	0.003	-10000	0	-10000	0	0
FOXO1/14-3-3 family	-0.001	0.13	-10000	0	-0.47	25	25
MST1	0.064	0.073	0.3	29	-10000	0	29
CSNK1D	0.021	0.004	-10000	0	-10000	0	0
CSNK1E	0.02	0.005	-10000	0	-10000	0	0
FOXO4/14-3-3 family	0.005	0.09	-10000	0	-0.38	16	16
YWHAB	0.02	0.005	-10000	0	-10000	0	0
MAPK8	0.026	0.061	0.2	48	-10000	0	48
MAPK9	0.026	0.063	0.2	47	-10000	0	47
YWHAG	0.02	0.004	-10000	0	-10000	0	0
YWHAE	0.019	0.006	-10000	0	-10000	0	0
YWHAZ	0.019	0.007	-10000	0	-10000	0	0
SIRT1	0.003	0.023	-10000	0	-10000	0	0
SOD2	0.12	0.18	0.45	43	-0.47	1	44
RBL2	0.13	0.21	0.52	33	-0.64	9	42
RAL/GDP	0.047	0.031	0.17	1	-10000	0	1
CHUK	0.054	0.043	0.17	10	-10000	0	10
Ran/GTP	0.016	0.009	0.22	1	-10000	0	1
CSNK1G2	0.02	0.006	-10000	0	-10000	0	0
RAL/GTP	0.046	0.03	0.19	1	-10000	0	1
CSNK1G1	0.021	0.004	-10000	0	-10000	0	0
FASLG	0.049	0.14	-10000	0	-1.1	6	6
SKP2	0.018	0.016	0.32	1	-10000	0	1
USP7	0.021	0.003	-10000	0	-10000	0	0
IKBKB	0.046	0.042	0.16	24	-10000	0	24
CCNB1	0.19	0.26	0.58	115	-10000	0	115
FOXO1-3a-4/beta catenin	0.12	0.15	0.41	52	-10000	0	52
proteasomal ubiquitin-dependent protein catabolic process	0.022	0.041	-10000	0	-10000	0	0
CSNK1A1	0.02	0.005	-10000	0	-10000	0	0
SGK1	0.052	0.045	0.18	11	-10000	0	11
CSNK1G3	0.02	0.005	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.029	0.01	0.21	1	-10000	0	1
ZFAND5	0.028	0.067	0.44	1	-10000	0	1
SFN	0.025	0.043	0.32	9	-0.33	1	10
CDK2	0.012	0.02	-10000	0	-10000	0	0
FOXO3A/14-3-3	0.046	0.11	0.26	17	-0.37	12	29
CREBBP	0.012	0.02	-10000	0	-10000	0	0
FBXO32	0.2	0.26	0.63	84	-10000	0	84
BCL6	0.13	0.22	0.51	38	-0.7	12	50
RALB	0.021	0.003	-10000	0	-10000	0	0
RALA	0.02	0.006	-10000	0	-10000	0	0
YWHAH	0.02	0.004	-10000	0	-10000	0	0

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.037	0.024	-10000	0	-0.17	3	3
NF kappa B1 p50/RelA/I kappa B alpha	-0.011	0.11	0.26	2	-0.34	21	23
AP1	0.006	0.072	-10000	0	-0.16	66	66
mol:PIP3	-0.036	0.044	-10000	0	-0.17	41	41
AKT1	-0.01	0.069	0.25	7	-0.3	7	14
PTK2B	-0.041	0.12	0.24	2	-0.35	38	40
RHOA	-0.006	0.075	0.18	7	-0.36	16	23
PIK3CB	0.02	0.006	-10000	0	-10000	0	0
mol:Ca2+	-0.029	0.085	0.21	10	-0.36	14	24
MAGI3	0.017	0.034	-10000	0	-0.33	5	5
RELA	0.021	0.004	-10000	0	-10000	0	0
apoptosis	-0.011	0.06	-10000	0	-0.19	48	48
HRAS/GDP	0.015	0.003	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.046	0.11	0.23	5	-0.36	28	33
NF kappa B1 p50/RelA	-0.05	0.082	-10000	0	-0.25	53	53
endothelial cell migration	-0.009	0.015	0.3	1	-10000	0	1
ADCY4	-0.013	0.054	0.24	1	-0.26	8	9
ADCY5	-0.023	0.07	0.22	2	-0.25	22	24
ADCY6	-0.009	0.047	0.24	1	-0.26	6	7
ADCY7	-0.01	0.044	-10000	0	-0.23	6	6
ADCY1	-0.009	0.048	0.24	1	-0.24	8	9
ADCY2	-0.015	0.057	0.24	1	-0.24	11	12
ADCY3	-0.008	0.043	0.24	1	-0.2	5	6
ADCY8	-0.056	0.082	-10000	0	-0.24	25	25
ADCY9	-0.012	0.053	0.24	1	-0.25	10	11
GSK3B	-0.042	0.11	0.21	7	-0.36	33	40
arachidonic acid secretion	-0.015	0.051	-10000	0	-0.29	9	9
GNG2	0.019	0.022	-10000	0	-0.32	2	2
TRIP6	0.01	0.025	-10000	0	-0.31	3	3
GNAO1	-0.009	0.021	0.16	5	-0.19	2	7
HRAS	0.021	0.004	-10000	0	-10000	0	0
NFKBIA	-0.029	0.11	0.24	7	-0.3	48	55
GAB1	0.02	0.022	-10000	0	-0.33	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	-0.018	0.21	-10000	0	-0.84	30	30
JUN	0.019	0.027	-10000	0	-0.33	3	3
LPA/LPA2/NHERF2	0.026	0.022	-10000	0	-0.18	5	5
TIAM1	-0.034	0.24	-10000	0	-0.99	30	30
PIK3R1	0.019	0.017	-10000	0	-0.32	1	1
mol:IP3	-0.022	0.072	0.21	10	-0.37	6	16
PLCB3	-0.013	0.031	0.18	10	-0.17	5	15
FOS	0.002	0.078	-10000	0	-0.33	27	27
positive regulation of mitosis	-0.015	0.051	-10000	0	-0.29	9	9
LPA/LPA1-2-3	0.021	0.065	0.22	4	-0.17	48	52
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0	-10000	0	-10000	0	0
BCAR1	0.02	0.016	-10000	0	-0.33	1	1
stress fiber formation	-0.022	0.091	0.24	3	-0.34	18	21
GNAZ	-0.023	0.048	0.12	1	-0.19	39	40
EGFR/PI3K-beta/Gab1	-0.035	0.047	-10000	0	-0.17	38	38
positive regulation of dendritic cell cytokine production	0.02	0.064	0.21	4	-0.17	48	52
LPA/LPA2/MAGI-3	0.025	0.023	-10000	0	-0.19	5	5
ARHGEF1	0.007	0.073	0.2	61	-0.17	1	62
GNAI2	-0.01	0.011	0.12	1	-0.19	1	2
GNAI3	-0.01	0.011	0.12	1	-0.19	1	2
GNAI1	-0.01	0.014	0.12	1	-0.19	2	3
LPA/LPA3	-0.004	0.071	0.22	4	-0.22	47	51
LPA/LPA2	0.016	0.005	-10000	0	-10000	0	0
LPA/LPA1	0.017	0.014	0.18	1	-0.22	1	2
HB-EGF/EGFR	-0.014	0.089	0.13	80	-0.2	55	135
HBEGF	-0.011	0.1	0.15	93	-0.22	70	163
mol:DAG	-0.022	0.072	0.21	10	-0.37	6	16
cAMP biosynthetic process	-0.019	0.061	0.3	2	-0.23	9	11
NFKB1	0.021	0.003	-10000	0	-10000	0	0
SRC	0.02	0.004	-10000	0	-10000	0	0
GNB1	0.02	0.006	-10000	0	-10000	0	0
LYN	-0.032	0.11	0.3	4	-0.28	55	59
GNAQ	-0.011	0.061	0.17	1	-0.2	44	45
LPAR2	0.02	0.005	-10000	0	-10000	0	0
LPAR3	-0.009	0.1	0.32	4	-0.33	47	51
LPAR1	0.021	0.017	-10000	0	-0.33	1	1
IL8	-0.021	0.12	0.29	16	-0.35	29	45
PTK2	-0.024	0.052	0.19	9	-0.17	2	11
Rac1/GDP	0.014	0.005	-10000	0	-10000	0	0
CASP3	-0.011	0.06	-10000	0	-0.2	48	48
EGFR	0.014	0.045	0.32	1	-0.33	8	9
PLCG1	-0.016	0.071	0.14	6	-0.23	43	49
PLD2	-0.024	0.056	0.19	13	-0.17	3	16
G12/G13	0.036	0.018	-10000	0	-10000	0	0
PI3K-beta	-0.024	0.049	-10000	0	-0.31	9	9
cell migration	-0.011	0.068	0.19	1	-0.25	27	28
SLC9A3R2	0.017	0.034	-10000	0	-0.33	5	5
PXN	-0.023	0.093	0.24	3	-0.35	18	21
HRAS/GTP	-0.015	0.051	-10000	0	-0.3	8	8
RAC1	0.019	0.007	-10000	0	-10000	0	0
MMP9	0.085	0.12	0.32	109	-10000	0	109
PRKCE	0.017	0.034	-10000	0	-0.33	5	5
PRKCD	-0.035	0.085	0.25	4	-0.34	17	21
Gi(beta/gamma)	-0.005	0.045	-10000	0	-0.25	4	4
mol:LPA	0.001	0.004	-10000	0	-10000	0	0
TRIP6/p130 Cas/FAK1/Paxillin	-0.01	0.084	0.3	1	-0.36	11	12
MAPKKK cascade	-0.015	0.051	-10000	0	-0.29	9	9
contractile ring contraction involved in cytokinesis	-0.005	0.077	0.19	8	-0.35	17	25
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.014	0.067	0.17	1	-0.2	52	53
GNA15	-0.009	0.057	0.17	1	-0.2	42	43
GNA12	0.019	0.007	-10000	0	-10000	0	0
GNA13	0.02	0.004	-10000	0	-10000	0	0
MAPT	-0.048	0.11	0.23	5	-0.37	28	33
GNA11	-0.01	0.057	-10000	0	-0.2	42	42
Rac1/GTP	-0.02	0.22	-10000	0	-0.89	30	30
MMP2	-0.009	0.015	0.3	1	-10000	0	1

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	-0.013	0.007	-10000	0	-10000	0	0
RAS family/GTP	0.002	0.085	-10000	0	-0.23	6	6
NFATC4	-0.04	0.068	0.24	11	-10000	0	11
ERBB2IP	0.02	0.009	-10000	0	-10000	0	0
HSP90 (dimer)	0.02	0.004	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.048	0.067	-10000	0	-0.2	69	69
JUN	-0.006	0.062	0.26	2	-10000	0	2
HRAS	0.02	0.006	-10000	0	-10000	0	0
DOCK7	-0.051	0.065	-10000	0	-0.2	6	6
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.002	0.071	0.2	2	-0.18	62	64
AKT1	-0.008	0.006	-10000	0	-10000	0	0
BAD	-0.013	0.005	-10000	0	-10000	0	0
MAPK10	-0.032	0.067	0.18	12	-0.2	17	29
mol:GTP	0	0.001	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.051	0.071	-10000	0	-0.21	69	69
RAF1	-0.011	0.094	0.26	14	-0.25	6	20
ErbB2/ErbB3/neuregulin 2	-0.012	0.066	0.19	2	-0.19	53	55
STAT3	0.003	0.13	-10000	0	-0.87	11	11
cell migration	-0.024	0.075	0.2	18	-0.2	14	32
mol:PI-3-4-5-P3	-0.001	0.002	-10000	0	-10000	0	0
cell proliferation	-0.028	0.18	0.42	2	-0.55	30	32
FOS	-0.022	0.15	0.32	4	-0.4	45	49
NRAS	0.02	0.007	-10000	0	-10000	0	0
mol:Ca2+	-0.048	0.067	-10000	0	-0.2	69	69
MAPK3	-0.016	0.15	0.39	3	-0.51	19	22
MAPK1	-0.027	0.17	0.39	3	-0.56	25	28
JAK2	-0.049	0.066	-10000	0	-0.22	8	8
NF2	-0.028	0.13	-10000	0	-0.61	25	25
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.018	0.071	0.2	3	-0.2	60	63
NRG1	-0.04	0.13	-10000	0	-0.33	85	85
GRB2/SOS1	0.03	0.007	-10000	0	-10000	0	0
MAPK8	-0.048	0.088	0.19	1	-0.23	60	61
MAPK9	-0.022	0.059	0.18	15	-10000	0	15
ERBB2	-0.019	0.02	0.27	2	-10000	0	2
ERBB3	0.014	0.025	-10000	0	-0.33	2	2
SHC1	0.019	0.016	0.32	1	-10000	0	1
RAC1	0.019	0.007	-10000	0	-10000	0	0
apoptosis	0.011	0.008	-10000	0	-10000	0	0
STAT3 (dimer)	0.004	0.13	-10000	0	-0.85	11	11
RNF41	-0.018	0.009	-10000	0	-10000	0	0
FRAP1	-0.007	0.004	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.042	0.045	-10000	0	-0.16	56	56
ErbB2/ErbB2/HSP90 (dimer)	-0.02	0.017	0.2	2	-10000	0	2
CHRNA1	-0.006	0.14	0.37	4	-0.47	21	25
myelination	-0.031	0.084	0.26	20	-10000	0	20
PPP3CB	-0.049	0.061	-10000	0	-0.19	6	6
KRAS	0.019	0.007	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.002	0.079	0.22	1	-0.2	5	6
NRG2	-0.018	0.11	-10000	0	-0.33	56	56
mol:GDP	-0.018	0.071	0.2	3	-0.2	60	63
SOS1	0.021	0.003	-10000	0	-10000	0	0
MAP2K2	-0.013	0.094	0.26	13	-0.28	6	19
SRC	0.02	0.004	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.002	-10000	0	-10000	0	0
PTPN11	-0.051	0.066	-10000	0	-0.2	6	6
MAP2K1	-0.035	0.17	0.39	1	-0.57	23	24
heart morphogenesis	-0.048	0.067	-10000	0	-0.2	69	69
RAS family/GDP	0.003	0.086	-10000	0	-0.22	6	6
GRB2	0.02	0.005	-10000	0	-10000	0	0
PRKACA	-0.027	0.15	-10000	0	-0.65	27	27
CHRNE	0.002	0.02	0.18	3	-10000	0	3
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
activation of caspase activity	0.008	0.006	-10000	0	-10000	0	0
nervous system development	-0.048	0.067	-10000	0	-0.2	69	69
CDC42	0.021	0.003	-10000	0	-10000	0	0

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	-0.035	0.061	0.24	8	-0.23	30	38
KIRREL	0.016	0.045	-10000	0	-0.34	8	8
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.035	0.061	0.23	30	-0.24	8	38
PLCG1	0.02	0.005	-10000	0	-10000	0	0
ARRB2	0.02	0.006	-10000	0	-10000	0	0
WASL	0.02	0.004	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	0.051	0.057	0.22	30	-0.18	8	38
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.014	0.041	0.16	2	-0.21	8	10
FYN	0.016	0.084	0.21	68	-0.17	8	76
mol:Ca2+	0.048	0.055	0.27	1	-0.18	8	9
mol:DAG	0.049	0.056	0.28	1	-0.18	8	9
NPHS2	-0.004	0.023	-10000	0	-10000	0	0
mol:IP3	0.049	0.056	0.28	1	-0.18	8	9
regulation of endocytosis	0.037	0.049	0.2	26	-0.17	8	34
Nephrin/NEPH1/podocin/Cholesterol	0.041	0.054	0.2	30	-0.18	8	38
establishment of cell polarity	0.035	0.061	0.23	30	-0.24	8	38
Nephrin/NEPH1/podocin/NCK1-2	0.06	0.058	0.28	1	-0.17	8	9
Nephrin/NEPH1/beta Arrestin2	0.038	0.051	0.2	26	-0.17	8	34
NPHS1	0.041	0.083	0.33	36	-10000	0	36
Nephrin/NEPH1/podocin	0.04	0.052	0.2	30	-0.18	8	38
TJP1	0.02	0.005	-10000	0	-10000	0	0
NCK1	0.021	0.003	-10000	0	-10000	0	0
NCK2	0.021	0.002	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.05	0.057	0.23	5	-0.18	8	13
CD2AP	0.02	0.004	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	0.05	0.057	0.22	29	-0.18	8	37
GRB2	0.02	0.004	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	0.006	0.093	0.22	61	-0.18	30	91
cytoskeleton organization	-0.003	0.053	0.22	11	-0.22	8	19
Nephrin/NEPH1	0.03	0.048	0.19	30	-0.16	8	38
Nephrin/NEPH1/ZO-1	0.04	0.053	0.22	26	-0.19	8	34

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	-0.018	0.029	-10000	0	-0.23	9	9
MAP4K4	-0.007	0.042	0.14	1	-0.26	5	6
BAG4	0.019	0.007	-10000	0	-10000	0	0
PKC zeta/ceramide	0.003	0.062	-10000	0	-0.18	52	52
NFKBIA	0.018	0.008	-10000	0	-10000	0	0
BIRC3	0.022	0.037	0.32	5	-0.33	2	7
BAX	-0.008	0.074	-10000	0	-0.35	20	20
RIPK1	0.021	0.004	-10000	0	-10000	0	0
AKT1	0.004	0.11	0.72	11	-10000	0	11
BAD	-0.012	0.06	0.2	4	-0.18	52	56
SMPD1	0.006	0.052	0.17	12	-0.21	5	17
RB1	-0.013	0.057	0.12	2	-0.18	52	54
FADD/Caspase 8	0.002	0.055	0.18	7	-0.28	6	13
MAP2K4	-0.014	0.059	0.18	8	-0.17	50	58
NSMAF	0.019	0.006	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.013	0.062	0.2	11	-0.17	50	61
EGF	0.071	0.12	0.32	91	-0.33	5	96
mol:ceramide	-0.008	0.062	0.12	6	-0.18	52	58
MADD	0.021	0.003	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.016	0.026	-10000	0	-0.23	7	7
ASAH1	0.017	0.017	-10000	0	-0.33	1	1
negative regulation of cell cycle	-0.013	0.056	0.12	2	-0.17	52	54
cell proliferation	0.002	0.066	0.2	5	-0.18	25	30
BID	-0.007	0.13	-10000	0	-0.59	20	20
MAP3K1	-0.01	0.062	0.18	10	-0.18	51	61
EIF2A	-0.014	0.066	0.2	17	-0.17	47	64
TRADD	0.02	0.004	-10000	0	-10000	0	0
CRADD	0.021	0.021	0.32	1	-0.33	1	2
MAPK3	-0.013	0.06	0.18	11	-0.17	34	45
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.017	0.063	0.19	10	-0.18	26	36
Cathepsin D/ceramide	0.003	0.063	-10000	0	-0.18	52	52
FADD	-0.006	0.041	0.15	2	-0.26	5	7
KSR1	-0.009	0.066	0.21	11	-0.18	52	63
MAPK8	-0.009	0.064	-10000	0	-0.25	6	6
PRKRA	-0.011	0.061	0.23	5	-0.18	50	55
PDGFA	0.014	0.043	-10000	0	-0.33	8	8
TRAF2	0.021	0.004	-10000	0	-10000	0	0
IGF1	0.014	0.052	0.32	1	-0.33	11	12
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.008	0.061	0.12	6	-0.18	52	58
CTSD	0.021	0.004	-10000	0	-10000	0	0
regulation of nitric oxide biosynthetic process	0.03	0.007	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	0.003	0.071	0.21	5	-0.19	25	30
PRKCD	0.02	0.004	-10000	0	-10000	0	0
PRKCZ	0.019	0.027	-10000	0	-0.33	3	3
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.016	0.026	-10000	0	-0.23	7	7
RelA/NF kappa B1	0.03	0.007	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.021	0.003	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.001	0.042	0.16	2	-0.28	3	5
TNFR1A/BAG4/TNF-alpha	0.029	0.042	0.22	1	-0.19	14	15
mol:Sphingosine-1-phosphate	-0.018	0.029	-10000	0	-0.23	9	9
MAP2K1	-0.015	0.061	0.18	14	-0.17	36	50
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.021	0.004	-10000	0	-10000	0	0
CYCS	0.004	0.051	0.18	3	-0.18	15	18
TNFRSF1A	0.02	0.005	-10000	0	-10000	0	0
NFKB1	0.021	0.003	-10000	0	-10000	0	0
TNFR1A/BAG4	0.026	0.012	-10000	0	-10000	0	0
EIF2AK2	-0.013	0.061	0.2	10	-0.17	47	57
TNF-alpha/TNFR1A/FAN	0.03	0.041	0.22	1	-0.2	13	14
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.014	0.045	-10000	0	-0.27	7	7
MAP2K2	-0.016	0.059	0.18	11	-0.17	42	53
SMPD3	0.008	0.057	0.19	5	-0.28	9	14
TNF	0.011	0.06	0.32	1	-0.33	15	16
PKC zeta/PAR4	0.028	0.021	-10000	0	-0.23	3	3
mol:PHOSPHOCHOLINE	-0.019	0.063	0.17	10	-0.15	44	54
NF kappa B1/RelA/I kappa B alpha	0.049	0.03	-10000	0	-0.17	2	2
AIFM1	-0.002	0.06	0.17	4	-0.19	15	19
BCL2	0.019	0.021	0.32	1	-0.33	1	2

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	-0.008	0.065	0.32	19	-10000	0	19
PI3K Class IB/PDE3B	0.008	0.066	-10000	0	-0.32	19	19
PDE3B	0.008	0.066	-10000	0	-0.33	19	19

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.02	0.006	-10000	0	-10000	0	0
SVIL	0.021	0.005	-10000	0	-10000	0	0
ZNF318	0.019	0.009	-10000	0	-10000	0	0
JMJD2C	0.007	0.028	0.13	26	-10000	0	26
T-DHT/AR/Ubc9	0.002	0.087	0.17	6	-0.2	70	76
CARM1	0.02	0.005	-10000	0	-10000	0	0
PRDX1	0.021	0.005	-10000	0	-10000	0	0
PELP1	0.019	0.007	-10000	0	-10000	0	0
CTNNB1	0.021	0.004	-10000	0	-10000	0	0
AKT1	0.02	0.007	-10000	0	-10000	0	0
PTK2B	0.017	0.017	-10000	0	-0.33	1	1
MED1	0.02	0.007	-10000	0	-10000	0	0
MAK	0.008	0.063	-10000	0	-0.33	17	17
response to oxidative stress	0	0.001	-10000	0	-10000	0	0
HIP1	0.019	0.027	-10000	0	-0.33	3	3
GSN	0.021	0.005	-10000	0	-10000	0	0
NCOA2	0.016	0.035	-10000	0	-0.33	5	5
NCOA6	0.021	0.005	-10000	0	-10000	0	0
DNA-PK	0.036	0.018	-10000	0	-10000	0	0
NCOA4	0.021	0.003	-10000	0	-10000	0	0
PIAS3	0.018	0.008	-10000	0	-10000	0	0
cell proliferation	-0.015	0.12	-10000	0	-0.59	19	19
XRCC5	0.02	0.006	-10000	0	-10000	0	0
UBE3A	0.02	0.006	-10000	0	-10000	0	0
T-DHT/AR/SNURF	-0.005	0.093	0.17	5	-0.2	84	89
FHL2	0.038	0.1	0.31	49	-10000	0	49
RANBP9	0.021	0.004	-10000	0	-10000	0	0
JMJD1A	-0.008	0.034	-10000	0	-0.12	41	41
CDK6	0.019	0.016	-10000	0	-0.33	1	1
TGFB1I1	0.019	0.027	-10000	0	-0.33	3	3
T-DHT/AR/CyclinD1	0.002	0.088	0.17	6	-0.2	68	74
XRCC6	0.02	0.007	-10000	0	-10000	0	0
T-DHT/AR	0.013	0.11	0.27	9	-0.21	71	80
CTDSP1	0.021	0.003	-10000	0	-10000	0	0
CTDSP2	0.019	0.008	-10000	0	-10000	0	0
BRCA1	0.022	0.014	0.32	1	-10000	0	1
TCF4	0.017	0.023	-10000	0	-0.33	2	2
CDKN2A	0.096	0.14	0.32	135	-10000	0	135
SRF	0.038	0.044	0.17	1	-10000	0	1
NKX3-1	-0.023	0.069	0.089	1	-0.22	42	43
KLK3	-0.006	0.059	-10000	0	-10000	0	0
TMF1	0.021	0.004	-10000	0	-10000	0	0
HNRNPA1	0.02	0.007	-10000	0	-10000	0	0
AOF2	0	0.002	-10000	0	-10000	0	0
APPL1	-0.016	0.006	-10000	0	-10000	0	0
T-DHT/AR/Caspase 8	0.002	0.087	0.17	5	-0.2	70	75
AR	-0.025	0.12	0.32	1	-0.33	69	70
UBA3	0.021	0.004	-10000	0	-10000	0	0
PATZ1	0.02	0.007	-10000	0	-10000	0	0
PAWR	0.021	0.003	-10000	0	-10000	0	0
PRKDC	0.019	0.008	-10000	0	-10000	0	0
PA2G4	0.02	0.007	-10000	0	-10000	0	0
UBE2I	0.021	0.004	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	0.003	0.078	0.16	5	-0.18	68	73
RPS6KA3	0.021	0.005	-10000	0	-10000	0	0
T-DHT/AR/ARA70	0.003	0.087	0.17	6	-0.2	69	75
LATS2	0.019	0.008	-10000	0	-10000	0	0
T-DHT/AR/PRX1	0.004	0.078	0.16	5	-0.18	69	74
Cyclin D3/CDK11 p58	0.015	0.004	-10000	0	-10000	0	0
VAV3	0.018	0.037	0.32	1	-0.33	5	6
KLK2	0.006	0.081	0.31	21	-0.35	4	25
CASP8	0.02	0.016	-10000	0	-0.33	1	1
T-DHT/AR/TIF2/CARM1	0.011	0.083	0.21	1	-0.18	63	64
TMPRSS2	-0.059	0.22	-10000	0	-0.74	44	44
CCND1	0.016	0.04	-10000	0	-0.33	7	7
PIAS1	0.021	0.005	-10000	0	-10000	0	0
mol:T-DHT	0.002	0.018	0.054	9	-0.057	18	27
CDC2L1	0	0	-10000	0	-10000	0	0
PIAS4	0.02	0.007	-10000	0	-10000	0	0
T-DHT/AR/CDK6	0.004	0.085	0.17	5	-0.2	66	71
CMTM2	-0.04	0.13	-10000	0	-0.33	89	89
SNURF	0.009	0.06	-10000	0	-0.33	16	16
ZMIZ1	0.02	0.025	-10000	0	-10000	0	0
CCND3	0.02	0.004	-10000	0	-10000	0	0
TGIF1	0.019	0.008	-10000	0	-10000	0	0
FKBP4	0.02	0.006	-10000	0	-10000	0	0

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.02	0.004	-10000	0	-10000	0	0
VLDLR	0.014	0.043	-10000	0	-0.33	8	8
LRPAP1	0.021	0.004	-10000	0	-10000	0	0
NUDC	0.021	0.003	-10000	0	-10000	0	0
RELN/LRP8	0.015	0.084	0.22	13	-0.2	62	75
CaM/Ca2+	0.015	0.003	-10000	0	-10000	0	0
KATNA1	0.019	0.006	-10000	0	-10000	0	0
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	-0.029	0.07	0.18	21	-0.18	56	77
IQGAP1/CaM	0.03	0.008	-10000	0	-10000	0	0
DAB1	0.023	0.036	0.32	7	-10000	0	7
IQGAP1	0.021	0.003	-10000	0	-10000	0	0
PLA2G7	0.024	0.044	0.32	8	-0.33	2	10
CALM1	0.02	0.005	-10000	0	-10000	0	0
DYNLT1	0.019	0.006	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	0.034	0.028	0.23	9	-10000	0	9
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0.021	0.003	-10000	0	-10000	0	0
CDK5R1	0.028	0.048	0.32	13	-10000	0	13
LIS1/Poliovirus Protein 3A	-0.012	0.004	-10000	0	-10000	0	0
CDK5R2	0.1	0.14	0.32	140	-10000	0	140
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	0.01	0.087	0.24	10	-0.2	64	74
YWHAE	0.019	0.006	-10000	0	-10000	0	0
NDEL1/14-3-3 E	0.002	0.092	0.29	20	-0.21	3	23
MAP1B	0.003	0.013	-10000	0	-0.22	1	1
RAC1	0.005	0.002	-10000	0	-10000	0	0
p35/CDK5	-0.029	0.073	0.19	26	-10000	0	26
RELN	-0.018	0.12	0.32	6	-0.33	62	68
PAFAH/LIS1	-0.014	0.035	0.24	8	-0.2	2	10
LIS1/CLIP170	-0.017	0.007	-10000	0	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.02	0.062	0.16	3	-10000	0	3
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.023	0.094	0.26	2	-0.3	23	25
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	-0.001	0.081	0.23	22	-0.22	4	26
LIS1/IQGAP1	-0.017	0.007	-10000	0	-10000	0	0
RHOA	0.005	0.002	-10000	0	-10000	0	0
PAFAH1B1	-0.015	0.006	-10000	0	-10000	0	0
PAFAH1B3	0.032	0.058	0.32	19	-10000	0	19
PAFAH1B2	0.02	0.005	-10000	0	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0.01	0.031	-10000	0	-0.18	4	4
NDEL1/Katanin 60/Dynein heavy chain	-0.001	0.093	0.29	19	-0.22	2	21
LRP8	0.027	0.042	0.32	10	-10000	0	10
NDEL1/Katanin 60	0.001	0.093	0.29	21	-0.22	3	24
P39/CDK5	0.018	0.12	0.2	128	-10000	0	128
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	-0.017	0.007	-10000	0	-10000	0	0
CDK5	-0.034	0.062	0.18	13	-0.17	55	68
PPP2R5D	0.02	0.004	-10000	0	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.014	0.006	-10000	0	-10000	0	0
CSNK2A1	0.02	0.005	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1	0.011	0.079	0.25	9	-0.18	62	71
RELN/VLDLR	0.02	0.087	0.23	12	-0.18	65	77
CDC42	0.005	0.002	-10000	0	-10000	0	0

Signaling events mediated by PTP1B

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
PDGFRB	0.02	0.004	-10000	0	-10000	0	0
Jak2/Leptin Receptor	-0.009	0.13	0.24	1	-0.37	42	43
PTP1B/AKT1	0.012	0.074	0.19	1	-0.31	11	12
FYN	0.019	0.016	-10000	0	-0.33	1	1
p210 bcr-abl/PTP1B	0.005	0.077	0.23	3	-0.32	12	15
EGFR	0.014	0.047	0.32	1	-0.33	8	9
EGF/EGFR	0.034	0.097	0.23	18	-0.35	8	26
CSF1	0.018	0.027	-10000	0	-0.33	3	3
AKT1	0.019	0.009	-10000	0	-10000	0	0
INSR	0.02	0.006	-10000	0	-10000	0	0
PTP1B/N-cadherin	0.03	0.093	0.23	36	-0.29	13	49
Insulin Receptor/Insulin	0.022	0.073	-10000	0	-0.34	7	7
HCK	0.005	0.07	-10000	0	-0.33	22	22
CRK	0.019	0.006	-10000	0	-10000	0	0
TYK2	0.001	0.073	0.27	3	-0.37	7	10
EGF	0.072	0.12	0.32	91	-0.33	5	96
YES1	0.02	0.005	-10000	0	-10000	0	0
CAV1	-0.057	0.11	0.24	4	-0.32	32	36
TXN	0.022	0.02	0.33	2	-10000	0	2
PTP1B/IRS1/GRB2	0.022	0.075	0.25	1	-0.34	7	8
cell migration	-0.005	0.077	0.32	12	-0.23	3	15
STAT3	0.021	0.003	-10000	0	-10000	0	0
PRLR	0.021	0.095	0.32	26	-0.33	18	44
ITGA2B	-0.008	0.11	0.32	5	-0.33	47	52
CSF1R	0.016	0.04	-10000	0	-0.33	7	7
Prolactin Receptor/Prolactin	0.029	0.074	0.24	33	-0.23	18	51
FGR	-0.004	0.089	-10000	0	-0.33	36	36
PTP1B/p130 Cas	0.013	0.076	0.25	1	-0.31	11	12
Crk/p130 Cas	0.021	0.077	0.25	1	-0.35	7	8
DOK1	0.001	0.083	0.24	2	-0.34	14	16
JAK2	-0.008	0.13	0.22	2	-0.36	42	44
Jak2/Leptin Receptor/Leptin	0.024	0.098	0.23	13	-0.33	11	24
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
PTPN1	0.005	0.078	0.23	3	-0.32	12	15
LYN	0.019	0.006	-10000	0	-10000	0	0
CDH2	0.043	0.096	0.32	46	-0.33	6	52
SRC	0.007	0.091	-10000	0	-0.42	18	18
ITGB3	0.028	0.073	0.32	23	-0.33	5	28
CAT1/PTP1B	-0.025	0.14	0.26	6	-0.39	44	50
CAPN1	0.021	0.005	-10000	0	-10000	0	0
CSK	0.021	0.004	-10000	0	-10000	0	0
PI3K	0.026	0.07	-10000	0	-0.29	7	7
mol:H2O2	0	0.003	-10000	0	-10000	0	0
STAT3 (dimer)	0.022	0.091	0.21	9	-0.29	14	23
negative regulation of transcription	-0.008	0.13	0.22	2	-0.36	42	44
FCGR2A	0.016	0.031	-10000	0	-0.33	4	4
FER	0.021	0.008	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	0.015	0.096	0.23	28	-0.24	51	79
BLK	0.064	0.11	0.32	80	-0.33	1	81
Insulin Receptor/Insulin/Shc	0.032	0.017	-10000	0	-10000	0	0
RHOA	0.021	0.005	-10000	0	-10000	0	0
LEPR	-0.016	0.11	-10000	0	-0.32	55	55
BCAR1	0.02	0.016	-10000	0	-0.33	1	1
p210 bcr-abl/Grb2	0.02	0.004	-10000	0	-10000	0	0
mol:NADPH	0.001	0.003	-10000	0	-10000	0	0
TRPV6	-0.04	0.16	0.22	4	-0.38	67	71
PRL	0.024	0.045	0.33	11	-10000	0	11
SOCS3	0.002	0.13	-10000	0	-1.1	7	7
SPRY2	0.018	0.023	-10000	0	-0.33	2	2
Insulin Receptor/Insulin/IRS1	0.038	0.015	-10000	0	-0.18	1	1
CSF1/CSF1R	0.02	0.082	-10000	0	-0.33	12	12
Ras protein signal transduction	0.008	0.12	0.57	20	-10000	0	20
IRS1	0.02	0.016	-10000	0	-0.33	1	1
INS	0.011	0.014	-10000	0	-10000	0	0
LEP	0.048	0.091	0.32	50	-10000	0	50
STAT5B	0.006	0.091	0.2	6	-0.3	23	29
STAT5A	0.005	0.091	0.2	6	-0.3	23	29
GRB2	0.02	0.004	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.016	0.074	0.25	1	-0.32	10	11
CSN2	0.018	0.063	0.56	1	-10000	0	1
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
LAT	0.014	0.065	-10000	0	-0.4	9	9
YBX1	0.024	0.005	-10000	0	-10000	0	0
LCK	0.02	0.026	0.32	1	-0.33	2	3
SHC1	0.018	0.016	0.32	1	-10000	0	1
NOX4	0.028	0.048	0.32	13	-10000	0	13

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	-0.012	0.036	0.21	2	-0.23	5	7
RFC1	-0.01	0.041	0.22	7	-0.2	11	18
PRKDC	-0.002	0.055	0.22	24	-0.2	4	28
RIPK1	0.023	0.006	-10000	0	-10000	0	0
CASP7	-0.012	0.091	-10000	0	-0.63	9	9
FASLG/FAS/FADD/FAF1	0.004	0.054	0.16	26	-0.25	4	30
MAP2K4	-0.063	0.14	0.24	3	-0.31	103	106
mol:ceramide	-0.021	0.078	-10000	0	-0.26	15	15
GSN	-0.013	0.035	0.2	1	-0.23	5	6
FASLG/FAS/FADD/FAF1/Caspase 8	-0.004	0.06	0.2	1	-0.29	3	4
FAS	0.005	0.043	-10000	0	-0.33	6	6
BID	-0.021	0.027	0.5	1	-0.18	2	3
MAP3K1	-0.032	0.1	0.25	3	-0.44	12	15
MAP3K7	0.011	0.018	-10000	0	-10000	0	0
RB1	-0.012	0.027	-10000	0	-0.19	11	11
CFLAR	0.023	0.005	-10000	0	-10000	0	0
HGF/MET	0.007	0.1	0.22	10	-0.23	69	79
ARHGDIB	-0.01	0.038	0.22	5	-0.23	4	9
FADD	0.009	0.023	-10000	0	-10000	0	0
actin filament polymerization	0.013	0.036	0.29	2	-0.2	1	3
NFKB1	-0.025	0.11	-10000	0	-0.62	7	7
MAPK8	-0.1	0.2	0.25	1	-0.46	118	119
DFFA	-0.012	0.033	0.21	2	-0.2	4	6
DNA fragmentation during apoptosis	-0.012	0.038	0.21	4	-0.24	1	5
FAS/FADD/MET	0.015	0.061	0.22	6	-0.21	20	26
CFLAR/RIP1	0.034	0.01	-10000	0	-10000	0	0
FAIM3	0.02	0.03	0.32	2	-0.33	2	4
FAF1	0.008	0.026	-10000	0	-10000	0	0
PARP1	-0.012	0.037	0.22	3	-0.2	13	16
DFFB	-0.011	0.036	0.22	4	-0.2	4	8
CHUK	-0.031	0.099	-10000	0	-0.59	7	7
FASLG	0.006	0.035	-10000	0	-0.33	3	3
FAS/FADD	0.012	0.041	-10000	0	-0.24	6	6
HGF	0.006	0.079	0.32	4	-0.33	24	28
LMNA	-0.007	0.053	0.18	24	-0.28	2	26
CASP6	-0.012	0.034	0.21	2	-0.2	11	13
CASP10	0.007	0.032	-10000	0	-0.33	2	2
CASP3	-0.005	0.024	0.19	1	-0.32	2	3
PTPN13	-0.014	0.1	-10000	0	-0.33	51	51
CASP8	-0.021	0.026	0.29	2	-0.23	3	5
IL6	-0.24	0.48	-10000	0	-1.1	120	120
MET	0.011	0.072	0.32	6	-0.33	18	24
ICAD/CAD	-0.014	0.041	0.3	4	-0.23	1	5
FASLG/FAS/FADD/FAF1/Caspase 10	-0.021	0.079	-10000	0	-0.26	15	15
activation of caspase activity by cytochrome c	-0.021	0.026	0.5	1	-0.18	2	3
PAK2	-0.008	0.044	0.21	10	-0.2	11	21
BCL2	0.019	0.021	0.32	1	-0.32	1	2

EPHB forward 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
Ephrin A5/EPHB2	0.045	0.061	0.22	52	-0.17	3	55
cell-cell adhesion	0.021	0.035	0.25	2	-10000	0	2
Ephrin B/EPHB2/RasGAP	0.063	0.069	0.22	49	-0.18	12	61
ITSN1	0.02	0.004	-10000	0	-10000	0	0
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
SHC1	0.018	0.016	0.32	1	-10000	0	1
Ephrin B1/EPHB3	0.028	0.028	0.21	7	-0.19	3	10
Ephrin B1/EPHB1	0.045	0.062	0.21	54	-0.22	5	59
HRAS/GDP	0.012	0.072	-10000	0	-0.24	15	15
Ephrin B/EPHB1/GRB7	0.06	0.069	-10000	0	-0.19	14	14
Endophilin/SYNJ1	-0.011	0.049	0.18	16	-0.3	1	17
KRAS	0.02	0.006	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	0.061	0.066	-10000	0	-0.19	11	11
endothelial cell migration	0.035	0.032	-10000	0	-0.17	9	9
GRB2	0.02	0.004	-10000	0	-10000	0	0
GRB7	0.019	0.022	-10000	0	-0.33	2	2
PAK1	-0.015	0.053	0.22	5	-0.3	2	7
HRAS	0.021	0.004	-10000	0	-10000	0	0
RRAS	-0.013	0.051	0.18	15	-0.3	2	17
DNM1	0.025	0.035	0.32	7	-10000	0	7
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.014	0.048	0.18	15	-0.26	2	17
lamellipodium assembly	-0.021	0.035	-10000	0	-0.25	2	2
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.012	0.056	0.24	2	-0.24	5	7
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
EPHB2	0.053	0.094	0.32	55	-10000	0	55
EPHB3	0.024	0.036	0.32	7	-10000	0	7
EPHB1	0.051	0.098	0.32	55	-0.33	3	58
EPHB4	0.02	0.005	-10000	0	-10000	0	0
mol:GDP	-0.009	0.055	0.22	6	-0.27	10	16
Ephrin B/EPHB2	0.055	0.065	0.21	51	-0.18	12	63
Ephrin B/EPHB3	0.04	0.043	0.21	6	-0.18	12	18
JNK cascade	-0.004	0.057	0.23	12	-0.31	1	13
Ephrin B/EPHB1	0.051	0.063	0.21	42	-0.19	12	54
RAP1/GDP	-0.013	0.08	0.23	17	-0.26	14	31
EFNB2	0.015	0.043	-10000	0	-0.33	8	8
EFNB3	0.019	0.026	0.32	1	-0.33	2	3
EFNB1	0.019	0.027	-10000	0	-0.33	3	3
Ephrin B2/EPHB1-2	0.067	0.083	0.23	93	-0.16	11	104
RAP1B	0.02	0.005	-10000	0	-10000	0	0
RAP1A	0.02	0.004	-10000	0	-10000	0	0
CDC42/GTP	0.039	0.067	0.2	5	-0.23	10	15
Rap1/GTP	-0.02	0.045	0.098	5	-0.25	2	7
axon guidance	0.044	0.061	0.21	52	-0.17	3	55
MAPK3	-0.003	0.047	0.24	3	-0.28	2	5
MAPK1	-0.003	0.043	0.23	2	-0.25	1	3
Rac1/GDP	-0.017	0.069	0.22	6	-0.26	14	20
actin cytoskeleton reorganization	-0.027	0.045	0.091	4	-0.21	7	11
CDC42/GDP	-0.014	0.079	0.23	16	-0.26	14	30
PI3K	0.039	0.033	-10000	0	-0.17	9	9
EFNA5	0.019	0.033	0.32	2	-0.33	3	5
Ephrin B2/EPHB4	0.022	0.028	-10000	0	-0.19	8	8
Ephrin B/EPHB2/Intersectin/N-WASP	0.008	0.062	0.18	4	-0.22	12	16
CDC42	0.021	0.003	-10000	0	-10000	0	0
RAS family/GTP	-0.023	0.04	-10000	0	-0.24	2	2
PTK2	0.058	0.19	0.53	69	-10000	0	69
MAP4K4	-0.004	0.057	0.23	12	-0.32	1	13
SRC	0.02	0.004	-10000	0	-10000	0	0
KALRN	0.019	0.027	-10000	0	-0.33	3	3
Intersectin/N-WASP	0.029	0.008	-10000	0	-10000	0	0
neuron projection morphogenesis	0.001	0.086	0.28	23	-0.29	3	26
MAP2K1	0.004	0.049	0.25	2	-0.29	2	4
WASL	0.02	0.004	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	0.085	0.083	0.24	100	-0.21	5	105
cell migration	0.012	0.078	0.26	12	-0.26	5	17
NRAS	0.02	0.005	-10000	0	-10000	0	0
SYNJ1	-0.011	0.049	0.18	16	-0.3	1	17
PXN	0.021	0.003	-10000	0	-10000	0	0
TF	0.007	0.069	0.18	28	-0.18	9	37
HRAS/GTP	0.04	0.052	0.19	1	-0.18	11	12
Ephrin B1/EPHB1-2	0.072	0.082	0.22	100	-0.21	5	105
cell adhesion mediated by integrin	0.015	0.04	0.19	11	-0.19	9	20
RAC1	0.019	0.007	-10000	0	-10000	0	0
mol:GTP	0.047	0.059	0.22	7	-0.18	11	18
RAC1-CDC42/GTP	-0.024	0.037	-10000	0	-0.26	2	2
RASA1	0.02	0.005	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.018	0.069	0.22	6	-0.26	14	20
ruffle organization	0.005	0.091	0.28	27	-0.25	2	29
NCK1	0.021	0.003	-10000	0	-10000	0	0
receptor internalization	-0.014	0.047	0.18	16	-0.29	1	17
Ephrin B/EPHB2/KALRN	0.063	0.072	0.22	51	-0.19	14	65
ROCK1	-0.011	0.033	0.18	12	-0.18	2	14
RAS family/GDP	-0.032	0.04	-10000	0	-0.22	8	8
Rac1/GTP	-0.018	0.043	0.11	5	-0.18	11	16
Ephrin B/EPHB1/Src/Paxillin	0.006	0.061	-10000	0	-0.22	12	12

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.02	0.005	-10000	0	-9999	0
PLK4	0.036	0.067	0.32	26	-9999	26
regulation of centriole replication	-0.007	0.039	0.16	26	-9999	26

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	0.03	0.1	0.25	32	-0.33	16	48
FYN	-0.004	0.11	0.24	12	-0.38	22	34
LAT/GRAP2/SLP76	0.01	0.1	0.26	3	-0.34	23	26
IKBKB	0.018	0.007	-10000	0	-10000	0	0
AKT1	-0.008	0.094	0.24	8	-0.3	27	35
B2M	0.018	0.013	-10000	0	-10000	0	0
IKBKG	-0.003	0.034	0.1	13	-0.1	8	21
MAP3K8	0.02	0.016	-10000	0	-0.33	1	1
mol:Ca2+	-0.017	0.014	0.039	9	-0.055	13	22
integrin-mediated signaling pathway	0.024	0.016	-10000	0	-0.19	2	2
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.013	0.12	0.24	5	-0.41	26	31
TRPV6	0.005	0.26	1.2	20	-0.51	1	21
CD28	0.019	0.017	-10000	0	-0.33	1	1
SHC1	0.017	0.12	0.26	43	-0.38	18	61
receptor internalization	-0.008	0.11	-10000	0	-0.38	29	29
PRF1	-0.04	0.24	-10000	0	-0.95	30	30
KRAS	0.02	0.006	-10000	0	-10000	0	0
GRB2	0.02	0.004	-10000	0	-10000	0	0
COT/AKT1	0.003	0.081	0.23	7	-0.26	22	29
LAT	-0.007	0.11	0.27	5	-0.37	25	30
EntrezGene:6955	-0.001	0.005	-10000	0	-0.031	3	3
CD3D	0.017	0.03	-10000	0	-0.34	3	3
CD3E	0.015	0.037	-10000	0	-0.34	5	5
CD3G	0.012	0.05	-10000	0	-0.33	10	10
RASGRP2	-0.009	0.037	-10000	0	-0.15	29	29
RASGRP1	-0.017	0.099	0.24	7	-0.3	29	36
HLA-A	-0.001	0.005	-10000	0	-10000	0	0
RASSF5	0.018	0.022	-10000	0	-0.33	2	2
RAP1A/GTP/RAPL	0.025	0.016	-10000	0	-0.19	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.011	0.047	0.12	30	-0.12	8	38
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.016	0.035	-10000	0	-0.15	18	18
PRKCA	-0.011	0.052	0.17	4	-0.2	13	17
GRAP2	0.011	0.057	-10000	0	-0.33	14	14
mol:IP3	0.012	0.085	0.17	42	-0.27	21	63
EntrezGene:6957	-0.001	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.011	0.083	0.15	1	-0.3	26	27
ORAI1	-0.023	0.21	0.4	5	-0.98	20	25
CSK	-0.005	0.11	0.22	5	-0.36	25	30
B7 family/CD28	0.014	0.12	-10000	0	-0.43	23	23
CHUK	0.021	0.003	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.008	0.12	-10000	0	-0.41	25	25
PTPN6	-0.01	0.1	0.21	4	-0.37	22	26
VAV1	-0.009	0.11	0.2	4	-0.37	26	30
Monovalent TCR/CD3	0.002	0.047	-10000	0	-0.27	11	11
CBL	0.02	0.005	-10000	0	-10000	0	0
LCK	-0.002	0.11	0.24	8	-0.39	19	27
PAG1	0	0.11	0.23	13	-0.36	23	36
RAP1A	0.02	0.004	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.007	0.11	0.2	1	-0.4	24	25
CD80	0.012	0.053	-10000	0	-0.33	12	12
CD86	0.013	0.049	-10000	0	-0.33	10	10
PDK1/CARD11/BCL10/MALT1	0.002	0.049	0.13	5	-0.18	15	20
HRAS	0.021	0.004	-10000	0	-10000	0	0
GO:0035030	-0.019	0.097	0.19	4	-0.33	30	34
CD8A	0.017	0.036	0.33	1	-0.33	4	5
CD8B	0.018	0.044	0.32	3	-0.34	5	8
PTPRC	0.012	0.051	-10000	0	-0.33	11	11
PDK1/PKC theta	-0.018	0.11	0.3	8	-0.34	29	37
CSK/PAG1	0	0.11	0.23	17	-0.35	23	40
SOS1	0.021	0.003	-10000	0	-10000	0	0
peptide-MHC class I	0.013	0.013	-10000	0	-10000	0	0
GRAP2/SLP76	0.012	0.11	0.23	1	-0.38	24	25
STIM1	-0.003	0.069	1.2	1	-10000	0	1
RAS family/GTP	0.011	0.054	0.17	7	-0.17	10	17
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.009	0.12	-10000	0	-0.4	29	29
mol:DAG	-0.021	0.062	0.09	8	-0.23	26	34
RAP1A/GDP	0.007	0.022	0.069	10	-0.062	4	14
PLCG1	0.02	0.005	-10000	0	-10000	0	0
CD247	0.016	0.024	-10000	0	-0.32	2	2
cytotoxic T cell degranulation	-0.038	0.23	-10000	0	-0.9	30	30
RAP1A/GTP	-0.001	0.015	-10000	0	-0.06	28	28
mol:PI-3-4-5-P3	-0.01	0.1	0.23	6	-0.34	26	32
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.016	0.1	0.22	14	-0.34	21	35
NRAS	0.02	0.005	-10000	0	-10000	0	0
ZAP70	0.017	0.038	-10000	0	-0.33	6	6
GRB2/SOS1	0.03	0.007	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.014	0.095	0.23	3	-0.33	23	26
MALT1	0.019	0.007	-10000	0	-10000	0	0
TRAF6	0.021	0.003	-10000	0	-10000	0	0
CD8 heterodimer	0.027	0.048	0.31	3	-0.3	7	10
CARD11	0.033	0.065	0.32	24	-10000	0	24
PRKCB	-0.015	0.058	0.13	1	-0.22	20	21
PRKCE	-0.013	0.055	0.17	4	-0.2	15	19
PRKCQ	-0.02	0.12	0.26	4	-0.37	32	36
LCP2	0.018	0.027	-10000	0	-0.33	3	3
BCL10	0.02	0.004	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.006	0.084	0.22	9	-0.26	27	36
IKK complex	0.005	0.048	0.2	13	-0.12	4	17
RAS family/GDP	-0.004	0.008	-10000	0	-0.039	3	3
MAP3K14	-0.008	0.063	0.19	7	-0.22	17	24
PDPK1	-0.008	0.092	0.26	10	-0.29	25	35
TCR/CD3/MHC I/CD8/Fyn	-0.016	0.12	-10000	0	-0.46	21	21

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.01	0.028	0.11	1	-0.21	3	4
NFATC2	-0.015	0.043	0.11	1	-0.21	18	19
NFATC3	-0.01	0.024	0.11	1	-10000	0	1
CD40LG	-0.037	0.14	0.35	7	-0.4	34	41
PTGS2	-0.039	0.15	0.34	11	-0.39	41	52
JUNB	0.018	0.027	-10000	0	-0.33	3	3
CaM/Ca2+/Calcineurin A alpha-beta B1	0.01	0.02	-10000	0	-10000	0	0
CaM/Ca2+	0.01	0.02	-10000	0	-10000	0	0
CALM1	0.013	0.02	-10000	0	-10000	0	0
JUN	0.012	0.034	-10000	0	-0.34	3	3
mol:Ca2+	-0.001	0.008	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.01	0.011	-10000	0	-10000	0	0
FOSL1	0.028	0.059	0.32	16	-0.33	3	19
CREM	0.02	0.004	-10000	0	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	0.015	0.094	0.28	15	-0.28	11	26
FOS	-0.004	0.079	-10000	0	-0.33	27	27
IFNG	-0.022	0.15	0.35	29	-0.37	27	56
AP-1/NFAT1-c-4	0.011	0.17	0.46	15	-0.41	25	40
FASLG	-0.03	0.13	0.35	7	-0.37	24	31
NFAT1-c-4/ICER1	0.006	0.064	0.26	1	-0.24	7	8
IL2RA	-0.02	0.15	0.34	37	-0.37	23	60
FKBP12/FK506	0.015	0.003	-10000	0	-10000	0	0
CSF2	-0.038	0.15	0.34	17	-0.39	42	59
JunB/Fra1/NFAT1-c-4	0.015	0.082	0.26	14	-0.24	11	25
IL4	-0.033	0.13	0.32	10	-0.37	23	33
IL2	0	0.11	-10000	0	-0.84	8	8
IL3	-0.016	0.14	-10000	0	-0.62	24	24
FKBP1A	0.02	0.005	-10000	0	-10000	0	0
BATF3	0.019	0.006	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.019	0.006	-10000	0	-10000	0	0

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	0.035	0.1	0.27	20	-0.36	10	30
IKBKB	0.024	0.092	0.25	7	-0.29	16	23
AKT1	0.033	0.076	0.23	30	-0.23	1	31
IKBKG	0.031	0.069	0.24	6	-0.26	8	14
CALM1	0.018	0.081	0.25	7	-0.41	7	14
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
MAP3K1	0.042	0.12	0.27	30	-0.46	8	38
MAP3K7	0.019	0.006	-10000	0	-10000	0	0
mol:Ca2+	0.019	0.085	0.21	2	-0.41	9	11
DOK1	0.021	0.002	-10000	0	-10000	0	0
AP-1	0.022	0.074	0.22	12	-0.24	6	18
LYN	0.019	0.006	-10000	0	-10000	0	0
BLNK	0.019	0.022	-10000	0	-0.33	2	2
SHC1	0.018	0.016	0.32	1	-10000	0	1
BCR complex	0.073	0.097	0.25	106	-0.32	2	108
CD22	0.012	0.072	0.24	15	-0.32	7	22
CAMK2G	0.014	0.077	0.25	6	-0.39	7	13
CSNK2A1	0.02	0.005	-10000	0	-10000	0	0
INPP5D	0.019	0.027	-10000	0	-0.33	3	3
SHC/GRB2/SOS1	-0.004	0.049	0.15	8	-10000	0	8
GO:0007205	0.019	0.087	0.22	1	-0.42	9	10
SYK	0.019	0.022	-10000	0	-0.33	2	2
ELK1	0.015	0.082	0.23	3	-0.46	6	9
NFATC1	0.036	0.093	0.26	20	-0.34	7	27
B-cell antigen/BCR complex	0.073	0.097	0.25	106	-0.32	2	108
PAG1/CSK	0.027	0.011	-10000	0	-10000	0	0
NFKBIB	0.023	0.04	0.14	6	-0.13	10	16
HRAS	0.022	0.073	0.23	9	-0.33	5	14
NFKBIA	0.022	0.04	0.14	6	-0.13	10	16
NF-kappa-B/RelA/I kappa B beta	0.025	0.036	0.14	6	-10000	0	6
RasGAP/Csk	0.082	0.083	0.24	101	-0.16	1	102
mol:GDP	0.018	0.088	0.21	2	-0.39	10	12
PTEN	0.021	0.003	-10000	0	-10000	0	0
CD79B	0.025	0.043	0.32	9	-0.33	1	10
NF-kappa-B/RelA/I kappa B alpha	0.025	0.036	0.14	6	-10000	0	6
GRB2	0.02	0.004	-10000	0	-10000	0	0
PI3K/BCAP/CD19	0.05	0.12	0.3	12	-0.49	7	19
PIK3R1	0.019	0.016	-10000	0	-0.33	1	1
mol:IP3	0.019	0.086	0.22	1	-0.42	9	10
CSK	0.021	0.004	-10000	0	-10000	0	0
FOS	0.006	0.085	0.26	5	-0.38	9	14
CHUK	0.027	0.076	0.25	4	-0.27	12	16
IBTK	0.019	0.006	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	0.037	0.076	-10000	0	-0.32	6	6
PTPN6	0.006	0.068	0.22	15	-0.38	5	20
RELA	0.021	0.004	-10000	0	-10000	0	0
BCL2A1	0.016	0.027	0.12	1	-10000	0	1
VAV2	0.049	0.09	0.27	16	-0.45	3	19
ubiquitin-dependent protein catabolic process	0.023	0.04	0.14	6	-0.13	11	17
BTK	-0.051	0.26	-10000	0	-0.98	38	38
CD19	0.047	0.088	0.26	25	-0.34	3	28
MAP4K1	0.017	0.031	-10000	0	-0.33	4	4
CD72	0.02	0.005	-10000	0	-10000	0	0
PAG1	0.019	0.007	-10000	0	-10000	0	0
MAPK14	0.043	0.11	0.27	36	-0.4	7	43
SH3BP5	0.018	0.031	-10000	0	-0.33	4	4
PIK3AP1	0.02	0.087	0.23	1	-0.43	9	10
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	0.018	0.13	-10000	0	-0.57	13	13
RAF1	0.018	0.069	0.23	6	-0.34	4	10
RasGAP/p62DOK/SHIP	0.078	0.078	0.35	8	-0.22	3	11
CD79A	0.08	0.13	0.32	105	-0.33	3	108
re-entry into mitotic cell cycle	0.021	0.073	0.22	12	-0.24	6	18
RASA1	0.02	0.005	-10000	0	-10000	0	0
MAPK3	0.012	0.066	0.22	6	-0.32	3	9
MAPK1	0.014	0.065	0.25	9	-0.35	2	11
CD72/SHP1	0.022	0.088	0.26	17	-0.35	5	22
NFKB1	0.021	0.003	-10000	0	-10000	0	0
MAPK8	0.039	0.11	0.26	35	-0.4	7	42
actin cytoskeleton organization	0.062	0.1	0.28	39	-0.42	2	41
NF-kappa-B/RelA	0.049	0.07	0.25	6	-0.21	6	12
Calcineurin	0.031	0.073	-10000	0	-0.37	5	5
PI3K	0.005	0.065	0.19	7	-0.28	5	12
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	0.024	0.078	0.25	1	-0.44	7	8
SOS1	0.021	0.003	-10000	0	-10000	0	0
Bam32/HPK1	0.037	0.12	-10000	0	-0.6	12	12
DAPP1	0.025	0.13	-10000	0	-0.66	12	12
cytokine secretion	0.035	0.09	0.25	20	-0.34	6	26
mol:DAG	0.019	0.086	0.22	1	-0.42	9	10
PLCG2	0.018	0.027	-10000	0	-0.33	3	3
MAP2K1	0.013	0.067	0.24	5	-0.31	4	9
B-cell antigen/BCR complex/FcgammaRIIB	0.074	0.088	0.24	102	-0.17	2	104
mol:PI-3-4-5-P3	0.017	0.068	0.19	21	-0.24	3	24
ETS1	0.011	0.073	0.24	9	-0.33	7	16
B-cell antigen/BCR complex/LYN/SYK/BLNK	0.084	0.085	0.24	101	-0.24	2	103
B-cell antigen/BCR complex/LYN	0.031	0.065	0.28	8	-0.36	4	12
MALT1	0.019	0.007	-10000	0	-10000	0	0
TRAF6	0.021	0.003	-10000	0	-10000	0	0
RAC1	0.058	0.098	0.28	35	-0.45	2	37
B-cell antigen/BCR complex/LYN/SYK	0.06	0.1	0.35	17	-0.31	5	22
CARD11	0.033	0.094	0.26	14	-0.4	7	21
FCGR2B	0.019	0.007	-10000	0	-10000	0	0
PPP3CA	0.021	0.003	-10000	0	-10000	0	0
BCL10	0.02	0.004	-10000	0	-10000	0	0
IKK complex	0.023	0.047	0.14	25	-0.12	5	30
PTPRC	0.012	0.05	-10000	0	-0.33	11	11
PDPK1	0.021	0.07	0.21	32	-0.21	1	33
PPP3CB	0.021	0.003	-10000	0	-10000	0	0
PPP3CC	0.018	0.008	-10000	0	-10000	0	0
POU2F2	0.019	0.026	0.12	5	-10000	0	5

Plasma membrane estrogen receptor signaling

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
GNB1/GNG2	0.041	0.041	0.21	7	-0.18	9	16
ER alpha/Gai/GDP/Gbeta gamma	-0.032	0.14	-10000	0	-0.45	31	31
AKT1	-0.061	0.24	-10000	0	-0.7	57	57
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.057	0.24	-10000	0	-0.7	58	58
mol:Ca2+	-0.02	0.066	-10000	0	-0.32	19	19
IGF1R	0.02	0.004	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	0.025	0.039	0.21	9	-0.19	9	18
SHC1	0.018	0.016	0.32	1	-10000	0	1
apoptosis	0.058	0.22	0.67	57	-10000	0	57
RhoA/GTP	-0.023	0.022	-10000	0	-0.15	6	6
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.016	0.12	0.24	1	-0.38	30	31
regulation of stress fiber formation	0.014	0.052	0.24	1	-0.24	2	3
E2/ERA-ERB (dimer)	0.025	0.039	0.21	9	-0.19	9	18
KRAS	0.02	0.006	-10000	0	-10000	0	0
G13/GTP	0.024	0.033	0.2	9	-0.17	7	16
pseudopodium formation	-0.014	0.052	0.24	2	-0.24	1	3
E2/ER alpha (dimer)/PELP1	0.025	0.037	0.21	9	-0.18	8	17
GRB2	0.02	0.004	-10000	0	-10000	0	0
GNG2	0.019	0.022	-10000	0	-0.33	2	2
GNAO1	0.021	0.035	0.32	4	-0.33	2	6
HRAS	0.021	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.038	0.16	0.24	3	-0.43	58	61
E2/ER beta (dimer)	0.015	0.011	-10000	0	-0.22	1	1
mol:GDP	-0.003	0.063	0.18	11	-0.19	34	45
mol:NADP	-0.038	0.16	0.24	3	-0.43	58	61
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
mol:IP3	-0.021	0.068	-10000	0	-0.34	19	19
IGF-1R heterotetramer	0.02	0.004	-10000	0	-10000	0	0
PLCB1	-0.006	0.063	-10000	0	-0.35	14	14
PLCB2	-0.008	0.067	-10000	0	-0.34	16	16
IGF1	0.014	0.052	0.32	1	-0.33	11	12
mol:L-citrulline	-0.038	0.16	0.24	3	-0.43	58	61
RHOA	0.02	0.004	-10000	0	-10000	0	0
Gai/GDP	-0.024	0.16	-10000	0	-0.61	31	31
JNK cascade	0.015	0.011	-10000	0	-0.22	1	1
BCAR1	0.02	0.016	-10000	0	-0.33	1	1
ESR2	0.02	0.016	-10000	0	-0.33	1	1
GNAQ	0.02	0.016	-10000	0	-0.33	1	1
ESR1	0.019	0.059	0.32	9	-0.33	8	17
Gq family/GDP/Gbeta gamma	-0.044	0.2	-10000	0	-0.72	39	39
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.013	0.059	-10000	0	-0.6	2	2
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.013	0.11	0.21	1	-0.37	27	28
GNAZ	-0.006	0.092	-10000	0	-0.33	39	39
E2/ER alpha (dimer)	0.014	0.04	0.22	9	-0.22	8	17
STRN	0.02	0.016	-10000	0	-0.33	1	1
GNAL	0.017	0.047	0.32	3	-0.33	7	10
PELP1	0.02	0.006	-10000	0	-10000	0	0
MAPK11	-0.013	0.017	0.22	1	-0.19	3	4
GNAI2	0.02	0.004	-10000	0	-10000	0	0
GNAI3	0.02	0.004	-10000	0	-10000	0	0
GNAI1	0.02	0.016	-10000	0	-0.33	1	1
HBEGF	-0.042	0.15	0.33	10	-0.43	39	49
cAMP biosynthetic process	0.018	0.038	0.14	11	-0.17	14	25
SRC	-0.032	0.13	0.28	1	-0.44	29	30
PI3K	0.029	0.014	-10000	0	-0.23	1	1
GNB1	0.021	0.004	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	0.019	0.063	-10000	0	-0.26	7	7
SOS1	0.021	0.003	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.024	0.09	-10000	0	-0.31	29	29
Gs family/GTP	0.023	0.041	0.17	11	-0.17	14	25
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.035	0.015	-10000	0	-10000	0	0
vasodilation	-0.036	0.15	0.23	3	-0.41	58	61
mol:DAG	-0.021	0.068	-10000	0	-0.34	19	19
Gs family/GDP/Gbeta gamma	0.001	0.061	-10000	0	-0.26	10	10
MSN	-0.015	0.054	0.24	2	-0.26	1	3
Gq family/GTP	0.002	0.068	-10000	0	-0.35	16	16
mol:PI-3-4-5-P3	-0.054	0.23	-10000	0	-0.68	58	58
NRAS	0.02	0.005	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.036	0.15	0.41	58	-0.23	3	61
GRB2/SOS1	0.03	0.007	-10000	0	-10000	0	0
RhoA/GDP	0.008	0.067	0.19	9	-0.25	10	19
NOS3	-0.041	0.17	0.24	2	-0.45	58	60
GNA11	0.019	0.016	-10000	0	-0.33	1	1
MAPKKK cascade	-0.032	0.16	0.32	2	-0.47	53	55
E2/ER alpha (dimer)/PELP1/Src	-0.019	0.12	0.24	5	-0.4	29	34
ruffle organization	-0.014	0.052	0.24	2	-0.24	1	3
ROCK2	-0.01	0.058	0.26	2	-10000	0	2
GNA14	0.013	0.05	-10000	0	-0.33	11	11
GNA15	0.02	0.006	-10000	0	-10000	0	0
GNA13	0.02	0.004	-10000	0	-10000	0	0
MMP9	-0.021	0.13	0.35	6	-0.41	28	34
MMP2	-0.033	0.13	0.27	7	-0.42	28	35

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	-0.015	0.1	0.28	2	-0.39	20	22
ACTA1	-0.02	0.092	0.29	4	-0.3	31	35
NUMA1	-0.009	0.085	0.28	2	-0.33	20	22
SPTAN1	-0.025	0.092	0.32	3	-0.3	34	37
LIMK1	-0.021	0.094	0.22	13	-0.3	32	45
BIRC3	0.022	0.037	0.32	5	-0.33	2	7
BIRC2	0.02	0.005	-10000	0	-10000	0	0
BAX	0.02	0.004	-10000	0	-10000	0	0
CASP10	-0.03	0.05	-10000	0	-0.22	31	31
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.021	0.003	-10000	0	-10000	0	0
PTK2	-0.011	0.084	0.26	2	-0.34	18	20
DIABLO	0.021	0.003	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.025	0.091	0.32	3	-0.3	34	37
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.021	0.021	0.32	1	-0.33	1	2
GSN	-0.026	0.093	0.33	3	-0.3	34	37
MADD	0.021	0.003	-10000	0	-10000	0	0
TFAP2A	0.088	0.14	0.38	1	-0.49	20	21
BID	-0.012	0.037	-10000	0	-0.16	29	29
MAP3K1	-0.015	0.091	0.21	1	-0.42	20	21
TRADD	0.02	0.004	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.03	0.008	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.023	0.092	0.26	5	-0.31	30	35
CASP9	0.021	0.004	-10000	0	-10000	0	0
DNA repair	0	0.04	0.17	6	-0.25	1	7
neuron apoptosis	-0.012	0.13	-10000	0	-0.63	20	20
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.017	0.094	0.29	3	-0.35	21	24
APAF1	0.021	0.004	-10000	0	-10000	0	0
CASP6	-0.006	0.11	-10000	0	-0.84	7	7
TRAF2	0.021	0.004	-10000	0	-10000	0	0
ICAD/CAD	-0.027	0.093	0.33	6	-0.3	31	37
CASP7	-0.004	0.064	0.24	2	-0.27	10	12
KRT18	0.013	0.028	-10000	0	-10000	0	0
apoptosis	-0.022	0.094	0.4	2	-0.38	19	21
DFFA	-0.025	0.092	0.25	5	-0.3	34	39
DFFB	-0.025	0.092	0.27	4	-0.3	33	37
PARP1	0	0.04	0.25	1	-0.18	6	7
actin filament polymerization	0.003	0.11	0.28	28	-0.31	20	48
TNF	0.011	0.06	0.32	1	-0.33	15	16
CYCS	0	0.045	0.15	11	-0.2	5	16
SATB1	-0.011	0.11	-10000	0	-0.75	8	8
SLK	-0.026	0.091	0.29	3	-0.3	34	37
p15 BID/BAX	0.004	0.053	0.19	2	-0.26	7	9
CASP2	0.002	0.051	0.19	14	-0.22	5	19
JNK cascade	0.015	0.09	0.41	20	-0.21	1	21
CASP3	-0.023	0.096	0.31	2	-0.31	35	37
LMNB2	-0.011	0.12	0.24	2	-0.39	35	37
RIPK1	0.021	0.004	-10000	0	-10000	0	0
CASP4	0.02	0.004	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	0.051	0.028	0.23	5	-0.18	2	7
negative regulation of DNA binding	0.088	0.14	0.38	1	-0.49	20	21
stress fiber formation	-0.026	0.09	0.29	3	-0.3	34	37
GZMB	-0.03	0.059	-10000	0	-0.25	31	31
CASP1	0.004	0.028	-10000	0	-0.25	6	6
LMNB1	-0.001	0.11	0.26	3	-0.42	20	23
APP	-0.012	0.13	-10000	0	-0.63	20	20
TNFRSF1A	0.02	0.005	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	-0.009	0.01	-10000	0	-0.22	1	1
VIM	-0.017	0.094	0.34	2	-0.38	19	21
LMNA	0.006	0.067	0.25	1	-0.34	7	8
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.003	0.047	-10000	0	-0.22	10	10
LRDD	0	0	-10000	0	-10000	0	0
SREBF1	-0.024	0.092	0.21	6	-0.3	34	40
APAF-1/Caspase 9	0.005	0.086	-10000	0	-0.64	8	8
nuclear fragmentation during apoptosis	-0.009	0.084	0.28	2	-0.32	20	22
CFL2	-0.003	0.11	0.31	20	-0.28	28	48
GAS2	-0.027	0.096	0.23	7	-0.3	35	42
positive regulation of apoptosis	-0.002	0.11	0.24	3	-0.41	19	22
PRF1	0.005	0.072	-10000	0	-0.33	23	23

IL12-mediated signaling events

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
IL12/IL12R/TYK2/JAK2/SOCS1	-0.011	0.094	-10000	0	-0.3	30	30
TBX21	-0.098	0.31	-10000	0	-1.2	29	29
B2M	0.02	0.009	-10000	0	-10000	0	0
TYK2	0.011	0.027	-10000	0	-10000	0	0
IL12RB1	0.003	0.061	-10000	0	-0.35	12	12
GADD45B	-0.09	0.28	-10000	0	-0.99	28	28
IL12RB2	0.033	0.091	0.32	39	-0.34	3	42
GADD45G	-0.082	0.27	-10000	0	-1	23	23
natural killer cell activation	-0.003	0.013	-10000	0	-0.048	6	6
RELB	0.02	0.004	-10000	0	-10000	0	0
RELA	0.021	0.004	-10000	0	-10000	0	0
IL18	0.007	0.051	-10000	0	-0.33	10	10
IL2RA	0.04	0.078	0.32	35	-0.33	1	36
IFNG	0.033	0.086	0.32	31	-0.33	8	39
STAT3 (dimer)	-0.072	0.23	-10000	0	-0.76	31	31
HLA-DRB5	-0.001	0.005	-10000	0	-0.022	24	24
FASLG	-0.071	0.27	-10000	0	-1	23	23
NF kappa B2 p52/RelB	-0.068	0.27	-10000	0	-0.91	28	28
CD4	0.012	0.047	-10000	0	-0.33	9	9
SOCS1	0.022	0.019	0.32	2	-10000	0	2
EntrezGene:6955	-0.001	0.008	0.025	1	-0.029	32	33
CD3D	0.015	0.032	-10000	0	-0.34	3	3
CD3E	0.014	0.037	-10000	0	-0.33	5	5
CD3G	0.01	0.051	-10000	0	-0.33	10	10
IL12Rbeta2/JAK2	0.03	0.069	0.24	31	-0.24	5	36
CCL3	-0.082	0.27	-10000	0	-1.1	21	21
CCL4	-0.083	0.27	-10000	0	-1	23	23
HLA-A	0	0.006	0.024	1	-0.05	6	7
IL18/IL18R	0.015	0.089	-10000	0	-0.25	39	39
NOS2	-0.13	0.38	-10000	0	-1.1	57	57
IL12/IL12R/TYK2/JAK2/SPHK2	-0.012	0.097	-10000	0	-0.31	32	32
IL1R1	-0.083	0.26	-10000	0	-1	22	22
IL4	0.003	0.027	-10000	0	-10000	0	0
JAK2	0.01	0.034	-10000	0	-0.32	2	2
EntrezGene:6957	-0.001	0.008	0.024	1	-0.028	29	30
TCR/CD3/MHC I/CD8	-0.018	0.14	-10000	0	-0.78	11	11
RAB7A	-0.073	0.23	-10000	0	-0.82	22	22
lysosomal transport	-0.069	0.22	-10000	0	-0.76	22	22
FOS	-0.084	0.29	-10000	0	-0.94	45	45
STAT4 (dimer)	-0.07	0.25	-10000	0	-0.88	26	26
STAT5A (dimer)	-0.063	0.27	-10000	0	-0.89	30	30
GZMA	-0.081	0.27	-10000	0	-1.1	21	21
GZMB	-0.092	0.3	-10000	0	-1.2	27	27
HLX	0.017	0.031	-10000	0	-0.33	4	4
LCK	-0.083	0.28	-10000	0	-1	28	28
TCR/CD3/MHC II/CD4	-0.011	0.069	-10000	0	-0.23	36	36
IL2/IL2R	0.057	0.057	0.23	35	-0.25	4	39
MAPK14	-0.088	0.28	-10000	0	-0.99	27	27
CCR5	-0.08	0.26	-10000	0	-1	22	22
IL1B	-0.009	0.088	-10000	0	-0.34	31	31
STAT6	-0.009	0.076	-10000	0	-0.32	2	2
STAT4	0.021	0.002	-10000	0	-10000	0	0
STAT3	0.021	0.003	-10000	0	-10000	0	0
STAT1	0.021	0.002	-10000	0	-10000	0	0
NFKB1	0.021	0.003	-10000	0	-10000	0	0
NFKB2	0.021	0.003	-10000	0	-10000	0	0
IL12B	0.014	0.042	0.31	5	-0.34	1	6
CD8A	0.018	0.035	0.32	1	-0.34	4	5
CD8B	0.019	0.043	0.32	3	-0.33	5	8
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.011	0.093	0.3	30	-10000	0	30
IL2RB	0.019	0.022	-10000	0	-0.33	2	2
proteasomal ubiquitin-dependent protein catabolic process	-0.062	0.23	-10000	0	-0.8	25	25
IL2RG	0.018	0.034	-10000	0	-0.33	5	5
IL12	0.02	0.048	0.22	5	-0.25	4	9
STAT5A	0.02	0.016	-10000	0	-0.33	1	1
CD247	0.015	0.026	-10000	0	-0.32	2	2
IL2	0.019	0.003	-10000	0	-10000	0	0
SPHK2	0.02	0.016	-10000	0	-0.33	1	1
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.009	0.046	0.33	1	-0.34	5	6
IL12/IL12R/TYK2/JAK2	-0.081	0.3	-10000	0	-1.1	28	28
MAP2K3	-0.094	0.29	-10000	0	-1	29	29
RIPK2	0.019	0.007	-10000	0	-10000	0	0
MAP2K6	-0.084	0.28	-10000	0	-0.98	27	27
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.001	0.006	-10000	0	-0.025	26	26
IL18RAP	0.001	0.07	-10000	0	-0.33	20	20
IL12Rbeta1/TYK2	0.013	0.053	-10000	0	-0.25	11	11
EOMES	-0.015	0.16	-10000	0	-0.68	22	22
STAT1 (dimer)	-0.058	0.24	-10000	0	-0.8	25	25
T cell proliferation	-0.058	0.19	-10000	0	-0.65	24	24
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0	0.073	-10000	0	-0.33	22	22
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.063	0.22	-10000	0	-0.66	32	32
ATF2	-0.082	0.26	-10000	0	-0.89	27	27

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

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
MET/RANBP9	0.023	0.052	0.23	6	-0.23	17	23
CRKL	-0.003	0.094	0.29	5	-0.43	11	16
mol:PIP3	0.007	0.038	-10000	0	-0.83	1	1
AKT1	0.002	0.05	-10000	0	-0.73	1	1
PTK2B	0.017	0.017	-10000	0	-0.33	1	1
RAPGEF1	-0.006	0.089	0.26	6	-0.4	11	17
RANBP10	0.02	0.004	-10000	0	-10000	0	0
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
HGF/MET/SHIP2	0.026	0.067	0.22	10	-0.2	36	46
MAP3K5	-0.004	0.096	0.27	6	-0.42	13	19
HGF/MET/CIN85/CBL/ENDOPHILINS	0.035	0.069	0.23	9	-0.18	37	46
AP1	-0.021	0.056	0.15	1	-0.21	24	25
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.018	0.016	0.32	1	-10000	0	1
apoptosis	-0.045	0.22	-10000	0	-0.71	48	48
STAT3 (dimer)	-0.012	0.077	0.22	1	-0.33	11	12
GAB1/CRKL/SHP2/PI3K	0.021	0.092	0.27	4	-0.38	12	16
INPP5D	0.019	0.027	-10000	0	-0.33	3	3
CBL/CRK	0.005	0.091	0.35	2	-0.39	11	13
PTPN11	0.021	0.004	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.02	0.005	-10000	0	-10000	0	0
PTEN	0.021	0.003	-10000	0	-10000	0	0
ELK1	0.004	0.091	0.29	38	-10000	0	38
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.004	0.046	0.14	1	-0.24	6	7
PAK1	0.005	0.062	0.39	2	-0.7	1	3
HGF/MET/RANBP10	0.025	0.069	0.22	10	-0.2	37	47
HRAS	-0.01	0.12	0.28	1	-0.5	22	23
DOCK1	-0.006	0.093	0.27	8	-0.42	11	19
GAB1	-0.003	0.088	0.23	2	-0.39	12	14
CRK	-0.007	0.092	0.37	2	-0.43	11	13
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.014	0.13	-10000	0	-0.42	41	41
JUN	0.019	0.027	-10000	0	-0.33	3	3
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.004	0.054	0.13	11	-0.18	38	49
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
cell morphogenesis	-0.013	0.097	0.3	12	-0.32	13	25
GRB2/SHC	0.018	0.054	0.21	1	-0.2	14	15
FOS	0.002	0.078	-10000	0	-0.33	27	27
GLMN	0.002	0.001	-10000	0	-10000	0	0
cell motility	0.004	0.091	0.29	38	-10000	0	38
HGF/MET/MUC20	0.013	0.066	0.21	10	-0.19	40	50
cell migration	0.017	0.053	0.2	1	-0.2	14	15
GRB2	0.02	0.004	-10000	0	-10000	0	0
CBL	0.02	0.005	-10000	0	-10000	0	0
MET/RANBP10	0.022	0.054	0.23	6	-0.23	18	24
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.01	0.068	0.18	1	-0.22	30	31
MET/MUC20	0.009	0.049	0.22	6	-0.22	18	24
RAP1B	0	0.091	0.26	9	-0.38	11	20
RAP1A	-0.009	0.085	0.26	6	-0.38	11	17
HGF/MET/RANBP9	0.025	0.07	0.22	10	-0.2	38	48
RAF1	-0.01	0.12	0.27	1	-0.47	23	24
STAT3	-0.012	0.078	0.23	1	-0.33	11	12
cell proliferation	0	0.11	0.29	19	-0.32	26	45
RPS6KB1	0.003	0.03	-10000	0	-0.25	2	2
MAPK3	-0.007	0.075	0.36	9	-10000	0	9
MAPK1	0.017	0.14	0.65	20	-10000	0	20
RANBP9	0.021	0.003	-10000	0	-10000	0	0
MAPK8	0	0.09	0.27	5	-0.36	13	18
SRC	-0.018	0.061	0.16	1	-0.28	9	10
PI3K	0.017	0.061	0.21	1	-0.2	23	24
MET/Glomulin	0.009	0.05	0.24	6	-0.19	18	24
SOS1	0.021	0.003	-10000	0	-10000	0	0
MAP2K1	-0.012	0.11	-10000	0	-0.44	23	23
MET	0.011	0.072	0.32	6	-0.33	18	24
MAP4K1	-0.002	0.1	0.29	6	-0.45	13	19
PTK2	0.018	0.007	-10000	0	-10000	0	0
MAP2K2	-0.012	0.11	-10000	0	-0.44	23	23
BAD	-0.001	0.052	0.4	1	-0.7	1	2
MAP2K4	-0.007	0.088	0.26	6	-0.38	13	19
SHP2/GRB2/SOS1/GAB1	0.008	0.088	-10000	0	-0.33	21	21
INPPL1	0.021	0.004	-10000	0	-10000	0	0
PXN	0.021	0.003	-10000	0	-10000	0	0
SH3KBP1	0.02	0.004	-10000	0	-10000	0	0
HGS	-0.013	0.048	0.14	5	-0.17	36	41
PLCgamma1/PKC	0.015	0.004	-10000	0	-10000	0	0
HGF	0.006	0.079	0.32	4	-0.33	24	28
RASA1	0.02	0.005	-10000	0	-10000	0	0
NCK1	0.021	0.003	-10000	0	-10000	0	0
PTPRJ	0.021	0.003	-10000	0	-10000	0	0
NCK/PLCgamma1	0.017	0.061	0.21	1	-0.18	35	36
PDPK1	0.004	0.045	-10000	0	-0.77	1	1
HGF/MET/SHIP	0.024	0.075	0.22	9	-0.21	39	48

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.019	0.043	-10000	0	-0.23	12	12
PDGFRB	0.015	0.015	-10000	0	-10000	0	0
SPHK1	0.002	0.049	-10000	0	-0.64	2	2
mol:S1P	-0.006	0.048	-10000	0	-0.55	2	2
S1P1/S1P/Gi	-0.038	0.13	-10000	0	-0.37	51	51
GNAO1	0.017	0.038	0.32	4	-0.33	2	6
PDGFB-D/PDGFRB/PLCgamma1	-0.032	0.13	0.26	5	-0.35	48	53
PLCG1	-0.045	0.12	0.28	1	-0.36	51	52
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.015	0.015	-10000	0	-10000	0	0
GNAI2	0.016	0.015	-10000	0	-10000	0	0
GNAI3	0.017	0.015	-10000	0	-10000	0	0
GNAI1	0.016	0.021	-10000	0	-0.33	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	-0.018	0.029	-10000	0	-0.2	12	12
S1P1/S1P	-0.019	0.058	0.21	1	-0.31	6	7
negative regulation of cAMP metabolic process	-0.037	0.13	-10000	0	-0.36	51	51
MAPK3	-0.061	0.17	0.26	8	-0.54	48	56
calcium-dependent phospholipase C activity	-0.001	0.003	-10000	0	-10000	0	0
Rac1/GDP	0.014	0.005	-10000	0	-10000	0	0
RhoA/GDP	0.015	0.003	-10000	0	-10000	0	0
KDR	0.009	0.054	-10000	0	-0.33	12	12
PLCB2	-0.015	0.064	0.21	6	-0.27	8	14
RAC1	0.019	0.007	-10000	0	-10000	0	0
RhoA/GTP	-0.023	0.046	-10000	0	-0.27	6	6
receptor internalization	-0.02	0.052	-10000	0	-0.29	6	6
PTGS2	-0.087	0.28	-10000	0	-0.91	48	48
Rac1/GTP	-0.022	0.044	-10000	0	-0.28	5	5
RHOA	0.02	0.004	-10000	0	-10000	0	0
VEGFA	0.017	0.014	-10000	0	-10000	0	0
negative regulation of T cell proliferation	-0.037	0.13	-10000	0	-0.36	51	51
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	-0.01	0.093	-10000	0	-0.33	39	39
MAPK1	-0.058	0.17	0.24	6	-0.54	47	53
S1P1/S1P/PDGFB-D/PDGFRB	-0.008	0.07	0.28	2	-0.27	9	11
ABCC1	0.017	0.014	-10000	0	-10000	0	0

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	0.037	0.05	0.23	23	-0.23	5	28
AKT1	-0.026	0.1	0.35	4	-0.42	15	19
PTK2B	-0.03	0.09	0.33	2	-0.44	13	15
VEGFR2 homodimer/Frs2	-0.012	0.095	-10000	0	-0.26	55	55
CAV1	-0.19	0.17	-10000	0	-0.33	311	311
CALM1	0.02	0.005	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.001	0.091	-10000	0	-0.44	12	12
endothelial cell proliferation	-0.024	0.12	0.35	10	-0.4	20	30
mol:Ca2+	-0.038	0.078	-10000	0	-0.41	12	12
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.009	0.092	-10000	0	-0.44	12	12
RP11-342D11.1	-0.035	0.08	0.16	13	-0.43	12	25
CDH5	-0.019	0.11	-10000	0	-0.33	58	58
VEGFA homodimer	0.042	0.024	-10000	0	-10000	0	0
SHC1	0.018	0.016	0.32	1	-10000	0	1
SHC2	0.015	0.043	0.32	1	-0.33	7	8
HRAS/GDP	0.005	0.076	-10000	0	-0.36	12	12
SH2D2A	0.018	0.007	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.019	0.13	-10000	0	-0.42	34	34
VEGFR2 homodimer/VEGFA homodimer/TsAd	0	0.093	-10000	0	-0.47	12	12
VEGFR1 homodimer	0.02	0.005	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.018	0.086	-10000	0	-0.39	12	12
GRB10	-0.037	0.078	-10000	0	-0.44	11	11
PTPN11	0.021	0.004	-10000	0	-10000	0	0
GRB2	0.02	0.004	-10000	0	-10000	0	0
PAK1	0.02	0.005	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.002	0.12	-10000	0	-0.4	26	26
HRAS	0.021	0.004	-10000	0	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	-0.012	0.078	0.2	1	-0.3	22	23
HIF1A	0.021	0.004	-10000	0	-10000	0	0
FRS2	0.02	0.005	-10000	0	-10000	0	0
oxygen and reactive oxygen species metabolic process	0.008	0.09	-10000	0	-0.43	12	12
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.012	0.055	-10000	0	-0.33	13	13
Nck/Pak	0.03	0.008	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.001	0.093	-10000	0	-0.46	12	12
mol:GDP	0.011	0.081	-10000	0	-0.38	12	12
mol:NADP	-0.026	0.13	0.36	6	-0.39	36	42
eNOS/Hsp90	-0.017	0.12	0.36	4	-0.37	35	39
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
mol:IP3	-0.038	0.079	-10000	0	-0.41	12	12
HIF1A/ARNT	0.025	0.013	-10000	0	-10000	0	0
SHB	0.02	0.006	-10000	0	-10000	0	0
VEGFA	0.021	0.004	-10000	0	-10000	0	0
VEGFC	0.02	0.029	0.32	2	-0.33	2	4
FAK1/Vinculin	-0.014	0.12	0.29	7	-0.45	18	25
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.02	0.004	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.018	0.11	0.32	1	-0.45	13	14
PTPN6	0.02	0.005	-10000	0	-10000	0	0
EPAS1	-0.022	0.12	-10000	0	-0.34	64	64
mol:L-citrulline	-0.026	0.13	0.36	6	-0.39	36	42
ITGAV	0.021	0.002	-10000	0	-10000	0	0
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.012	0.089	-10000	0	-0.41	12	12
VEGFR2 homodimer/VEGFA homodimer	0.002	0.094	-10000	0	-0.47	12	12
VEGFR2/3 heterodimer	-0.017	0.11	-10000	0	-0.5	16	16
VEGFB	0.021	0.003	-10000	0	-10000	0	0
MAPK11	-0.028	0.093	0.33	4	-0.45	12	16
VEGFR2 homodimer	-0.046	0.1	-10000	0	-0.3	58	58
FLT1	0.02	0.005	-10000	0	-10000	0	0
NEDD4	0.02	0.016	-10000	0	-0.32	1	1
MAPK3	-0.028	0.093	0.32	8	-0.4	12	20
MAPK1	-0.028	0.09	0.28	10	-0.4	11	21
VEGFA145/NRP2	0.029	0.02	-10000	0	-0.22	3	3
VEGFR1/2 heterodimer	-0.013	0.098	-10000	0	-0.51	12	12
KDR	-0.046	0.1	-10000	0	-0.3	58	58
VEGFA165/NRP1/VEGFR2 homodimer	0.003	0.089	-10000	0	-0.45	12	12
SRC	0.02	0.004	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	-0.026	0.097	0.29	12	-0.41	12	24
PI3K	-0.04	0.086	-10000	0	-0.47	12	12
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.002	0.094	-10000	0	-0.47	12	12
FES	-0.04	0.082	-10000	0	-0.45	12	12
GAB1	-0.026	0.098	-10000	0	-0.44	15	15
VEGFR2 homodimer/VEGFA homodimer/Src	0.001	0.093	-10000	0	-0.46	12	12
CTNNB1	0.021	0.004	-10000	0	-10000	0	0
SOS1	0.021	0.003	-10000	0	-10000	0	0
ARNT	0.017	0.008	-10000	0	-10000	0	0
eNOS/Caveolin-1	-0.09	0.13	-10000	0	-0.44	39	39
VEGFR2 homodimer/VEGFA homodimer/Yes	0.001	0.093	-10000	0	-0.47	12	12
PI3K/GAB1	-0.015	0.1	-10000	0	-0.44	14	14
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.022	0.092	-10000	0	-0.41	12	12
PRKACA	0.02	0.005	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.005	0.1	-10000	0	-0.46	16	16
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
CDC42	-0.039	0.082	-10000	0	-0.45	12	12
actin cytoskeleton reorganization	0	0.092	-10000	0	-0.47	12	12
PTK2	-0.026	0.11	0.32	2	-0.43	24	26
EDG1	-0.035	0.08	0.16	13	-0.43	12	25
mol:DAG	-0.038	0.079	-10000	0	-0.41	12	12
CaM/Ca2+	-0.037	0.073	-10000	0	-0.39	12	12
MAP2K3	-0.034	0.079	-10000	0	-0.39	12	12
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.012	0.1	-10000	0	-0.44	12	12
PLCG1	-0.039	0.08	-10000	0	-0.42	12	12
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.01	0.091	-10000	0	-0.42	12	12
IQGAP1	0.021	0.003	-10000	0	-10000	0	0
YES1	0.02	0.005	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	0	0.095	-10000	0	-0.47	12	12
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.001	0.092	-10000	0	-0.46	12	12
cell migration	-0.017	0.12	0.31	6	-0.43	20	26
mol:PI-3-4-5-P3	-0.038	0.08	-10000	0	-0.44	12	12
FYN	0.019	0.016	-10000	0	-0.33	1	1
VEGFB/NRP1	-0.037	0.076	-10000	0	-0.42	12	12
mol:NO	-0.026	0.13	0.36	6	-0.39	36	42
PXN	0.021	0.003	-10000	0	-10000	0	0
HRAS/GTP	-0.042	0.062	-10000	0	-0.36	12	12
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.041	0.075	-10000	0	-0.45	11	11
VHL	0.02	0.005	-10000	0	-10000	0	0
ITGB3	0.031	0.072	0.32	23	-0.33	5	28
NOS3	-0.03	0.14	0.39	5	-0.43	36	41
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.002	0.099	-10000	0	-0.45	15	15
RAC1	0.019	0.007	-10000	0	-10000	0	0
PRKCA	-0.037	0.078	-10000	0	-0.41	11	11
PRKCB	-0.039	0.086	0.33	1	-0.43	12	13
VCL	0.021	0.003	-10000	0	-10000	0	0
VEGFA165/NRP1	-0.035	0.08	-10000	0	-0.44	12	12
VEGFR1/2 heterodimer/VEGFA homodimer	0	0.094	-10000	0	-0.47	12	12
VEGFA165/NRP2	0.029	0.02	-10000	0	-0.22	3	3
MAPKKK cascade	-0.027	0.087	0.31	3	-0.41	8	11
NRP2	0.019	0.027	-10000	0	-0.33	3	3
VEGFC homodimer	0.02	0.029	0.32	2	-0.32	2	4
NCK1	0.021	0.003	-10000	0	-10000	0	0
ROCK1	0.02	0.005	-10000	0	-10000	0	0
FAK1/Paxillin	-0.014	0.12	0.28	6	-0.45	19	25
MAP3K13	-0.036	0.079	-10000	0	-0.42	12	12
PDPK1	-0.038	0.075	0.24	2	-0.39	12	14

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

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
MAP4K1	-0.014	0.09	0.42	2	-0.37	20	22
CRKL	-0.017	0.086	0.36	2	-0.38	23	25
HRAS	-0.006	0.078	-10000	0	-0.36	13	13
mol:PIP3	0.003	0.1	0.32	3	-0.4	20	23
SPRED1	0.02	0.005	-10000	0	-10000	0	0
SPRED2	0.021	0.001	-10000	0	-10000	0	0
GAB1	-0.015	0.093	0.32	1	-0.4	24	25
FOXO3	-0.003	0.11	0.33	1	-0.39	26	27
AKT1	0	0.12	0.26	1	-0.41	26	27
BAD	-0.003	0.11	-10000	0	-0.39	26	26
megakaryocyte differentiation	-0.026	0.1	-10000	0	-0.39	28	28
GSK3B	-0.002	0.11	0.25	1	-0.39	26	27
RAF1	-0.006	0.074	0.22	3	-0.3	13	16
SHC1	0.018	0.016	0.32	1	-10000	0	1
STAT3	-0.016	0.095	0.32	1	-0.4	25	26
STAT1	-0.043	0.21	0.44	1	-0.94	24	25
HRAS/SPRED1	0.008	0.075	-10000	0	-0.3	13	13
cell proliferation	-0.015	0.09	-10000	0	-0.39	24	24
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
TEC	0.021	0.004	-10000	0	-10000	0	0
RPS6KB1	-0.003	0.11	-10000	0	-0.41	25	25
HRAS/SPRED2	0.008	0.076	-10000	0	-0.3	13	13
LYN/TEC/p62DOK	0.019	0.096	0.31	1	-0.39	20	21
MAPK3	0	0.066	0.29	3	-0.23	6	9
STAP1	-0.019	0.097	0.32	1	-0.4	25	26
GRAP2	0.011	0.057	-10000	0	-0.33	14	14
JAK2	-0.039	0.19	0.42	1	-0.82	24	25
STAT1 (dimer)	-0.041	0.21	0.44	1	-0.92	24	25
mol:Gleevec	0	0.004	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	0.018	0.096	0.28	1	-0.4	17	18
actin filament polymerization	-0.013	0.083	0.32	1	-0.38	19	20
LYN	0.019	0.006	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.033	0.14	0.36	1	-0.57	25	26
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
CBL/CRKL/GRB2	0.007	0.086	0.41	2	-0.37	16	18
PI3K	0.015	0.1	-10000	0	-0.41	21	21
PTEN	0.021	0.003	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.023	0.23	-10000	0	-1.1	23	23
MAPK8	-0.016	0.092	-10000	0	-0.4	24	24
STAT3 (dimer)	-0.015	0.093	0.32	1	-0.39	25	26
positive regulation of transcription	0.001	0.059	0.23	5	-0.2	4	9
mol:GDP	0	0.08	-10000	0	-0.38	13	13
PIK3C2B	-0.014	0.094	0.44	2	-0.42	19	21
CBL/CRKL	-0.002	0.091	0.42	2	-0.37	20	22
FER	-0.015	0.093	0.32	1	-0.4	24	25
SH2B3	-0.015	0.093	0.32	1	-0.41	24	25
PDPK1	0.001	0.098	0.31	4	-0.37	19	23
SNAI2	-0.012	0.089	0.32	1	-0.41	20	21
positive regulation of cell proliferation	-0.034	0.16	0.4	1	-0.69	25	26
KITLG	0.014	0.037	-10000	0	-0.35	4	4
cell motility	-0.034	0.16	0.4	1	-0.69	25	26
PTPN6	0.019	0.011	-10000	0	-10000	0	0
EPOR	-0.019	0.16	-10000	0	-0.8	10	10
STAT5A (dimer)	-0.025	0.14	0.38	1	-0.56	26	27
SOCS1	0.022	0.019	0.32	2	-10000	0	2
cell migration	0.02	0.094	0.4	25	-10000	0	25
SOS1	0.021	0.003	-10000	0	-10000	0	0
EPO	0.02	0.029	0.32	4	-10000	0	4
VAV1	0.018	0.027	-10000	0	-0.33	3	3
GRB10	-0.015	0.089	0.33	1	-0.41	20	21
PTPN11	0.019	0.01	-10000	0	-10000	0	0
SCF/KIT	-0.01	0.1	0.35	1	-0.41	25	26
GO:0007205	0.001	0.005	-10000	0	-10000	0	0
MAP2K1	-0.004	0.066	0.22	6	-0.24	11	17
CBL	0.02	0.005	-10000	0	-10000	0	0
KIT	-0.035	0.25	0.47	1	-1.1	25	26
MAP2K2	-0.003	0.065	0.22	6	-0.24	12	18
SHC/Grb2/SOS1	0.016	0.088	-10000	0	-0.41	14	14
STAT5A	-0.024	0.14	0.38	1	-0.58	26	27
GRB2	0.02	0.004	-10000	0	-10000	0	0
response to radiation	-0.012	0.087	0.32	1	-0.4	20	21
SHC/GRAP2	0.023	0.028	-10000	0	-0.23	5	5
PTPRO	-0.025	0.1	-10000	0	-0.41	26	26
SH2B2	-0.013	0.085	0.32	1	-0.39	19	20
DOK1	0.021	0.002	-10000	0	-10000	0	0
MATK	-0.019	0.095	-10000	0	-0.42	24	24
CREBBP	0.02	0.033	0.29	1	-10000	0	1
BCL2	-0.039	0.19	0.47	1	-0.71	22	23

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.02	0.004	-10000	0	-10000	0	0
Syndecan-3/Src/Cortactin	0.03	0.072	0.29	2	-0.3	2	4
Syndecan-3/Neurocan	0.025	0.047	0.27	7	-0.28	3	10
POMC	0.014	0.072	0.32	7	-0.33	17	24
EGFR	0.014	0.045	0.32	1	-0.33	8	9
Syndecan-3/EGFR	0.016	0.035	0.3	1	-0.29	3	4
AGRP	-0.12	0.17	-10000	0	-0.33	208	208
NCSTN	0.019	0.007	-10000	0	-10000	0	0
PSENEN	0.02	0.005	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
APH1B	0.019	0.022	-10000	0	-0.33	2	2
APH1A	0.017	0.008	-10000	0	-10000	0	0
NCAN	0.029	0.053	0.32	16	-10000	0	16
long-term memory	0.037	0.037	-10000	0	-0.29	2	2
Syndecan-3/IL8	0.025	0.047	0.25	5	-0.29	3	8
PSEN1	0.021	0.004	-10000	0	-10000	0	0
Src/Cortactin	0.029	0.009	-10000	0	-10000	0	0
FYN	0.019	0.016	-10000	0	-0.33	1	1
limb bud formation	0.005	0.018	-10000	0	-0.4	1	1
MC4R	0.038	0.075	0.32	33	-10000	0	33
SRC	0.02	0.004	-10000	0	-10000	0	0
PTN	-0.018	0.12	0.32	6	-0.33	61	67
FGFR/FGF/Syndecan-3	0.005	0.018	-10000	0	-0.4	1	1
neuron projection morphogenesis	-0.01	0.073	0.34	7	-0.37	1	8
Syndecan-3/AgRP	-0.036	0.081	-10000	0	-0.31	4	4
Syndecan-3/AgRP/MC4R	-0.022	0.1	0.28	3	-0.33	3	6
Fyn/Cortactin	0.028	0.011	-10000	0	-10000	0	0
SDC3	0.005	0.019	-10000	0	-0.41	1	1
GO:0007205	0	0	-10000	0	-10000	0	0
positive regulation of leukocyte migration	0.025	0.047	0.25	5	-0.29	3	8
IL8	0.029	0.059	0.32	17	-0.33	2	19
Syndecan-3/Fyn/Cortactin	0.038	0.038	-10000	0	-0.3	2	2
Syndecan-3/CASK	0.003	0.024	-10000	0	-0.29	3	3
alpha-MSH/MC4R	0.033	0.07	0.23	35	-0.21	17	52
Gamma Secretase	0.046	0.031	-10000	0	-0.18	1	1

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	0.026	0.012	-10000	0	-0.19	1	1
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0.021	0.004	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.028	0.056	0.32	15	-0.33	2	17
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.02	0.006	-10000	0	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.015	0.032	0.16	7	-0.16	2	9
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.02	0.005	-10000	0	-10000	0	0
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	0.02	0.016	-10000	0	-0.33	1	1
FYN	0.019	0.016	-10000	0	-0.33	1	1
MAP3K12	0.021	0.003	-10000	0	-10000	0	0
FGR	-0.004	0.089	-10000	0	-0.33	36	36
p38 alpha/TAB1	-0.036	0.085	-10000	0	-0.29	37	37
PRKG1	-0.022	0.11	-10000	0	-0.33	63	63
DUSP8	0.015	0.046	-10000	0	-0.33	9	9
PGK/cGMP/p38 alpha	-0.018	0.12	-10000	0	-0.32	45	45
apoptosis	-0.035	0.082	-10000	0	-0.28	37	37
RAL/GTP	0.026	0.009	-10000	0	-10000	0	0
LYN	0.019	0.006	-10000	0	-10000	0	0
DUSP1	-0.008	0.095	-10000	0	-0.33	42	42
PAK1	0.02	0.005	-10000	0	-10000	0	0
SRC	0.02	0.004	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.043	0.024	-10000	0	-0.16	1	1
TRAF6	0.021	0.003	-10000	0	-10000	0	0
RAC1	0.019	0.007	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
mol:cGMP	0	0	-10000	0	-10000	0	0
CCM2	0.019	0.006	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0.025	0.01	-10000	0	-10000	0	0
MAPK11	-0.002	0.12	0.25	13	-0.31	37	50
BLK	0.064	0.11	0.32	80	-0.33	1	81
HCK	0.005	0.07	-10000	0	-0.33	22	22
MAP2K3	0.02	0.006	-10000	0	-10000	0	0
DUSP16	0.02	0.005	-10000	0	-10000	0	0
DUSP10	0.018	0.022	-10000	0	-0.33	2	2
TRAF6/MEKK3	0.025	0.011	-10000	0	-0.17	1	1
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	-0.002	0.12	0.23	11	-0.35	29	40
positive regulation of innate immune response	-0.003	0.14	0.28	13	-0.37	36	49
LCK	0.02	0.026	0.32	1	-0.33	2	3
p38alpha-beta/MKP7	0.006	0.14	0.28	12	-0.36	33	45
p38alpha-beta/MKP5	0.004	0.13	0.29	9	-0.37	30	39
PGK/cGMP	-0.014	0.078	-10000	0	-0.22	63	63
PAK2	0.02	0.005	-10000	0	-10000	0	0
p38alpha-beta/MKP1	-0.002	0.14	0.29	11	-0.36	39	50
CDC42	0.021	0.003	-10000	0	-10000	0	0
RALB	0.021	0.003	-10000	0	-10000	0	0
RALA	0.019	0.006	-10000	0	-10000	0	0
PAK3	0.053	0.1	0.32	60	-0.33	5	65

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.028	0.021	0.23	1	-0.23	2	3
ATM	0.02	0.005	-10000	0	-10000	0	0
UBE2D3	0.021	0.003	-10000	0	-10000	0	0
PRKDC	0.019	0.006	-10000	0	-10000	0	0
ATR	0.021	0.003	-10000	0	-10000	0	0
UBE2L3	0.02	0.005	-10000	0	-10000	0	0
FANCD2	0.011	0.013	0.21	1	-10000	0	1
protein ubiquitination	0.1	0.078	0.34	3	-0.17	1	4
XRCC5	0.021	0.003	-10000	0	-10000	0	0
XRCC6	0.02	0.004	-10000	0	-10000	0	0
M/R/N Complex	0.035	0.017	-10000	0	-10000	0	0
MRE11A	0.02	0.004	-10000	0	-10000	0	0
DNA-PK	0.037	0.015	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	-0.001	0.088	-10000	0	-0.47	12	12
FANCF	0.021	0.003	-10000	0	-10000	0	0
BRCA1	0.021	0.014	0.32	1	-10000	0	1
CCNE1	0.12	0.14	0.32	165	-10000	0	165
CDK2/Cyclin E1	0.092	0.096	0.23	159	-10000	0	159
FANCG	0.02	0.005	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.03	0.022	0.23	2	-0.23	2	4
FANCE	0.021	0.004	-10000	0	-10000	0	0
FANCC	0.02	0.005	-10000	0	-10000	0	0
NBN	0.019	0.007	-10000	0	-10000	0	0
FANCA	0.032	0.059	0.32	20	-10000	0	20
DNA repair	0.004	0.068	0.22	6	-0.36	5	11
BRCA1/BARD1/ubiquitin	0.03	0.022	0.23	2	-0.23	2	4
BARD1/DNA-PK	0.047	0.024	-10000	0	-0.18	2	2
FANCL	0.021	0.002	-10000	0	-10000	0	0
mRNA polyadenylation	-0.028	0.02	0.23	2	-0.23	1	3
BRCA1/BARD1/CTIP/M/R/N Complex	0.013	0.039	-10000	0	-0.21	7	7
BRCA1/BACH1/BARD1/TopBP1	0.041	0.021	0.22	2	-0.2	2	4
BRCA1/BARD1/P53	0.048	0.025	0.23	1	-0.18	2	3
BARD1/CSTF1/BRCA1	0.039	0.023	0.22	2	-0.2	2	4
BRCA1/BACH1	0.021	0.014	0.32	1	-10000	0	1
BARD1	0.02	0.026	0.32	1	-0.33	2	3
PCNA	0.021	0.014	0.32	1	-10000	0	1
BRCA1/BARD1/UbcH5C	0.041	0.021	0.22	2	-0.2	2	4
BRCA1/BARD1/UbcH7	0.038	0.019	-10000	0	-0.2	2	2
BRCA1/BARD1/RAD51/PCNA	0.075	0.072	0.23	78	-0.18	2	80
BARD1/DNA-PK/P53	0.05	0.03	-10000	0	-0.18	2	2
BRCA1/BARD1/Ubiquitin	0.03	0.022	0.23	2	-0.23	2	4
BRCA1/BARD1/CTIP	0.027	0.02	0.21	2	-0.17	2	4
FA complex	0.01	0.043	0.22	2	-0.19	12	14
BARD1/EWS	0.029	0.02	0.23	1	-0.23	2	3
RBBP8	-0.015	0.005	-10000	0	-10000	0	0
TP53	0.02	0.006	-10000	0	-10000	0	0
TOPBP1	0.021	0.003	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.046	0.024	0.18	2	-0.22	1	3
BRCA1/BARD1	0.11	0.085	0.23	151	-0.18	1	152
CSTF1	0.02	0.005	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.015	0.017	0.22	1	-0.22	2	3
CDK2	0.021	0.004	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.069	0.11	0.32	82	-10000	0	82
RAD50	0.02	0.005	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.03	0.022	0.23	2	-0.23	2	4
EWSR1	0.02	0.004	-10000	0	-10000	0	0

Signaling events mediated by HDAC Class III

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
EP300	0.02	0.005	-10000	0	-10000	0	0
HDAC4	0.021	0.003	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.003	0.051	-10000	0	-0.2	27	27
CDKN1A	-0.011	0.004	-10000	0	-10000	0	0
KAT2B	0.02	0.004	-10000	0	-10000	0	0
BAX	0.02	0.004	-10000	0	-10000	0	0
FOXO3	-0.003	0.002	-10000	0	-10000	0	0
FOXO1	0.02	0.005	-10000	0	-10000	0	0
FOXO4	0.006	0.002	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.02	0.004	-10000	0	-10000	0	0
TAT	0.047	0.086	0.32	45	-10000	0	45
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.016	0.014	0.16	3	-10000	0	3
PPARGC1A	-0.062	0.15	0.32	1	-0.33	123	124
FHL2	0.059	0.1	0.32	64	-10000	0	64
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.029	0.012	0.25	1	-10000	0	1
HIST2H4A	-0.003	0.051	0.2	27	-10000	0	27
SIRT1/FOXO3a	0.013	0.028	0.24	1	-0.2	4	5
SIRT1	0.021	0.015	0.35	1	-10000	0	1
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.036	0.019	0.24	1	-10000	0	1
SIRT1/Histone H1b	0.024	0.039	0.32	1	-0.22	4	5
apoptosis	-0.039	0.015	-10000	0	-0.23	1	1
SIRT1/PGC1A	-0.024	0.093	0.22	2	-0.19	120	122
p53/SIRT1	0.027	0.025	0.55	1	-10000	0	1
SIRT1/FOXO4	0.016	0.034	0.24	1	-0.22	4	5
FOXO1/FHL2/SIRT1	0.058	0.058	0.21	62	-10000	0	62
HIST1H1E	0.015	0.031	0.23	1	-10000	0	1
SIRT1/p300	0.029	0.012	0.25	1	-10000	0	1
muscle cell differentiation	-0.024	0.02	-10000	0	-0.21	5	5
TP53	0.019	0.016	0.35	1	-10000	0	1
KU70/SIRT1/BAX	0.039	0.015	0.24	1	-10000	0	1
CREBBP	0.021	0.004	-10000	0	-10000	0	0
MEF2D	0.018	0.008	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.046	0.057	0.23	43	-10000	0	43
ACSS2	-0.016	0.017	0.27	1	-0.23	1	2
SIRT1/PCAF/MYOD	0.025	0.02	0.21	5	-10000	0	5

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.024	0.018	-10000	0	-10000	0	0
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.021	0.11	0.39	18	-10000	0	18
IL27/IL27R/JAK1	0.029	0.092	-10000	0	-0.88	1	1
TBX21	-0.024	0.11	0.9	1	-0.55	5	6
IL12B	0.023	0.034	0.32	5	-0.33	1	6
IL12A	-0.009	0.023	0.16	1	-0.22	5	6
IL6ST	0.006	0.069	-10000	0	-0.33	20	20
IL27RA/JAK1	0.008	0.057	0.38	1	-1.1	1	2
IL27	0.009	0.059	-10000	0	-0.33	14	14
TYK2	0.021	0.015	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.016	0.12	0.44	2	-10000	0	2
T-helper 2 cell differentiation	0.021	0.11	0.39	18	-10000	0	18
T cell proliferation during immune response	0.021	0.11	0.39	18	-10000	0	18
MAPKKK cascade	-0.021	0.11	-10000	0	-0.39	18	18
STAT3	0.021	0.003	-10000	0	-10000	0	0
STAT2	0.021	0.004	-10000	0	-10000	0	0
STAT1	0.02	0.009	-10000	0	-10000	0	0
IL12RB1	0.012	0.053	-10000	0	-0.33	12	12
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.014	0.11	0.38	10	-0.5	4	14
IL27/IL27R/JAK2/TYK2	-0.022	0.11	-10000	0	-0.39	18	18
positive regulation of T cell mediated cytotoxicity	-0.021	0.11	-10000	0	-0.39	18	18
STAT1 (dimer)	0.026	0.12	-10000	0	-0.58	5	5
JAK2	0.019	0.025	-10000	0	-0.32	2	2
JAK1	0.02	0.009	-10000	0	-10000	0	0
STAT2 (dimer)	-0.013	0.12	0.45	1	-0.39	19	20
T cell proliferation	-0.046	0.13	0.34	2	-0.39	34	36
IL12/IL12R/TYK2/JAK2	-0.035	0.24	-10000	0	-0.82	40	40
IL17A	-0.019	0.12	0.44	2	-10000	0	2
mast cell activation	0.021	0.11	0.39	18	-10000	0	18
IFNG	0.001	0.042	0.11	33	-0.11	20	53
T cell differentiation	-0.001	0.005	0.013	8	-0.02	14	22
STAT3 (dimer)	-0.014	0.12	0.45	1	-0.39	18	19
STAT5A (dimer)	-0.015	0.12	0.45	1	-0.38	22	23
STAT4 (dimer)	-0.014	0.12	0.45	1	-0.37	23	24
STAT4	0.021	0.002	-10000	0	-10000	0	0
T cell activation	-0.003	0.006	0.11	1	-10000	0	1
IL27R/JAK2/TYK2	0.026	0.077	-10000	0	-0.61	2	2
GATA3	-0.002	0.094	0.63	7	-1.1	1	8
IL18	-0.011	0.03	-10000	0	-0.22	10	10
positive regulation of mast cell cytokine production	-0.014	0.12	0.45	1	-0.38	18	19
IL27/EBI3	0.023	0.049	-10000	0	-0.23	15	15
IL27RA	-0.001	0.056	0.32	1	-1.1	1	2
IL6	-0.046	0.14	-10000	0	-0.32	101	101
STAT5A	0.02	0.016	-10000	0	-0.33	1	1
monocyte differentiation	0	0.002	-10000	0	-10000	0	0
IL2	-0.008	0.032	0.4	2	-10000	0	2
IL1B	-0.021	0.051	-10000	0	-0.22	31	31
EBI3	0.02	0.021	-10000	0	-0.32	1	1
TNF	-0.013	0.037	0.16	1	-0.22	15	16

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
GNAO1	0.021	0.035	0.32	4	-0.33	2	6
CDC42/GTP	-0.011	0.076	-10000	0	-0.25	14	14
PLCG1	-0.018	0.065	0.27	1	-0.22	20	21
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.02	0.004	-10000	0	-10000	0	0
GNAI3	0.02	0.004	-10000	0	-10000	0	0
G12/G13	0.027	0.011	-10000	0	-10000	0	0
cell migration	-0.011	0.075	-10000	0	-0.25	14	14
S1PR5	0.001	0.081	0.32	1	-0.33	29	30
S1PR4	0.007	0.064	-10000	0	-0.33	18	18
MAPK3	-0.019	0.064	-10000	0	-0.22	19	19
MAPK1	-0.016	0.058	-10000	0	-0.2	15	15
S1P/S1P5/Gi	-0.015	0.075	-10000	0	-0.22	33	33
GNAI1	0.02	0.016	-10000	0	-0.33	1	1
CDC42/GDP	0.015	0.002	-10000	0	-10000	0	0
S1P/S1P5/G12	0.013	0.049	0.21	1	-0.19	26	27
RHOA	-0.001	0.074	0.19	54	-0.17	14	68
S1P/S1P4/Gi	-0.012	0.07	-10000	0	-0.21	27	27
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	-0.006	0.092	-10000	0	-0.33	39	39
S1P/S1P4/G12/G13	0.027	0.039	-10000	0	-0.18	15	15
GNA12	0.019	0.007	-10000	0	-10000	0	0
GNA13	0.02	0.004	-10000	0	-10000	0	0
CDC42	0.021	0.003	-10000	0	-10000	0	0

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.014	0.079	0.27	14	-10000	0	14
GNAI2	0.02	0.004	-10000	0	-10000	0	0
S1P/S1P5/G12	0.013	0.049	0.21	1	-0.19	26	27
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.021	0.035	0.32	4	-0.33	2	6
RhoA/GTP	-0.014	0.08	-10000	0	-0.28	14	14
negative regulation of cAMP metabolic process	-0.016	0.075	-10000	0	-0.22	35	35
GNAZ	-0.006	0.092	-10000	0	-0.33	39	39
GNAI3	0.02	0.004	-10000	0	-10000	0	0
GNA12	0.019	0.007	-10000	0	-10000	0	0
S1PR5	0.001	0.081	0.32	1	-0.33	29	30
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.015	0.075	-10000	0	-0.22	33	33
RhoA/GDP	0.015	0.003	-10000	0	-10000	0	0
RHOA	0.02	0.004	-10000	0	-10000	0	0
GNAI1	0.02	0.016	-10000	0	-0.33	1	1

Signaling events mediated by PRL

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
CCNE1	0.12	0.14	0.32	165	-10000	0	165
mol:Halofuginone	0.001	0	-10000	0	-10000	0	0
ITGA1	0.019	0.022	-10000	0	-0.33	2	2
CDKN1A	0.005	0.025	-10000	0	-0.32	2	2
PRL-3/alpha Tubulin	0.028	0.014	0.23	1	-10000	0	1
mol:Ca2+	0.001	0.063	0.16	59	-0.23	6	65
AGT	0.059	0.11	0.32	72	-0.33	5	77
CCNA2	-0.006	0.055	0.35	6	-10000	0	6
TUBA1B	0.021	0.003	-10000	0	-10000	0	0
EGR1	-0.016	0.046	-10000	0	-0.22	24	24
CDK2/Cyclin E1	0.086	0.096	0.35	9	-0.3	3	12
MAPK3	-0.014	0.016	0.21	2	-10000	0	2
PRL-2 /Rab GGTase beta	0.03	0.007	-10000	0	-10000	0	0
MAPK1	-0.013	0.016	0.21	2	-10000	0	2
PTP4A1	-0.02	0.031	-10000	0	-10000	0	0
PTP4A3	0.019	0.015	0.32	1	-10000	0	1
PTP4A2	0.021	0.002	-10000	0	-10000	0	0
ITGB1	-0.014	0.01	0.15	1	-10000	0	1
SRC	0.02	0.004	-10000	0	-10000	0	0
RAC1	0.004	0.032	-10000	0	-0.45	2	2
Rab GGTase beta/Rab GGTase alpha	0.029	0.009	-10000	0	-10000	0	0
PRL-1/ATF-5	-0.018	0.045	-10000	0	-10000	0	0
RABGGTA	0.02	0.005	-10000	0	-10000	0	0
BCAR1	-0.018	0.016	-10000	0	-0.23	2	2
RHOC	0.003	0.041	-10000	0	-0.37	5	5
RHOA	0	0.048	-10000	0	-0.34	9	9
cell motility	0.005	0.062	0.27	3	-0.31	8	11
PRL-1/alpha Tubulin	-0.019	0.043	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	0.026	0.019	0.23	1	-0.23	1	2
ROCK1	0.004	0.052	0.27	3	-0.33	5	8
RABGGTB	0.021	0.004	-10000	0	-10000	0	0
CDK2	0.021	0.004	-10000	0	-10000	0	0
mitosis	-0.02	0.031	-10000	0	-10000	0	0
ATF5	0.021	0.014	0.32	1	-10000	0	1

IL2 signaling events mediated by STAT5

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
GAB2	0.017	0.034	-10000	0	-0.33	5	5
ELF1	0.032	0.039	-10000	0	-10000	0	0
CCNA2	0.089	0.13	0.32	115	-10000	0	115
PIK3CA	0.021	0.004	-10000	0	-10000	0	0
JAK3	0.02	0.005	-10000	0	-10000	0	0
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
JAK1	0.021	0.003	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.016	0.07	-10000	0	-0.4	4	4
SHC1	0.019	0.016	0.32	1	-10000	0	1
SP1	0.017	0.043	-10000	0	-0.3	9	9
IL2RA	0.008	0.079	0.3	35	-10000	0	35
IL2RB	0.019	0.022	-10000	0	-0.33	2	2
SOS1	0.021	0.003	-10000	0	-10000	0	0
IL2RG	0.018	0.034	-10000	0	-0.33	5	5
G1/S transition of mitotic cell cycle	0.028	0.1	0.3	21	-0.42	11	32
PTPN11	0.021	0.004	-10000	0	-10000	0	0
CCND2	-0.024	0.076	-10000	0	-0.59	9	9
LCK	0.02	0.026	0.32	1	-0.33	2	3
GRB2	0.02	0.004	-10000	0	-10000	0	0
IL2	0.02	0.003	-10000	0	-10000	0	0
CDK6	0.02	0.016	-10000	0	-0.33	1	1
CCND3	0.018	0.078	0.42	2	-0.38	3	5

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.011	0.061	0.28	2	-10000	0	2
DAPP1	-0.018	0.12	0.21	4	-0.34	39	43
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.034	0.17	-10000	0	-0.47	46	46
mol:DAG	-0.014	0.071	0.19	8	-0.21	22	30
HRAS	0.021	0.007	-10000	0	-10000	0	0
RAP1A	0.021	0.007	-10000	0	-10000	0	0
ARF5/GDP	-0.003	0.091	-10000	0	-0.32	22	22
PLCG2	0.018	0.027	-10000	0	-0.33	3	3
PLCG1	0.02	0.005	-10000	0	-10000	0	0
ARF5	0.02	0.004	-10000	0	-10000	0	0
mol:GTP	-0.017	0.047	0.21	5	-10000	0	5
ARF1/GTP	-0.01	0.043	0.24	4	-10000	0	4
RHOA	0.02	0.004	-10000	0	-10000	0	0
YES1	0.02	0.005	-10000	0	-10000	0	0
RAP1A/GTP	-0.016	0.047	0.15	32	-10000	0	32
ADAP1	-0.017	0.048	0.25	4	-0.28	1	5
ARAP3	-0.016	0.046	0.2	5	-10000	0	5
INPPL1	0.021	0.004	-10000	0	-10000	0	0
PREX1	0.017	0.031	-10000	0	-0.33	4	4
ARHGEF6	0.008	0.066	-10000	0	-0.33	19	19
ARHGEF7	0.02	0.005	-10000	0	-10000	0	0
ARF1	0.02	0.006	-10000	0	-10000	0	0
NRAS	0.02	0.007	-10000	0	-10000	0	0
FYN	0.019	0.016	-10000	0	-0.33	1	1
ARF6	0.02	0.004	-10000	0	-10000	0	0
FGR	-0.004	0.089	-10000	0	-0.33	36	36
mol:Ca2+	-0.01	0.039	0.14	4	-0.13	7	11
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.015	0.043	-10000	0	-0.33	8	8
ZAP70	0.017	0.037	-10000	0	-0.33	6	6
mol:IP3	-0.016	0.052	0.14	9	-0.16	19	28
LYN	0.019	0.006	-10000	0	-10000	0	0
ARF1/GDP	0	0.085	0.18	1	-0.3	22	23
RhoA/GDP	-0.01	0.063	0.2	7	-0.26	4	11
PDK1/Src/Hsp90	0.039	0.013	-10000	0	-10000	0	0
BLNK	0.02	0.022	-10000	0	-0.33	2	2
actin cytoskeleton reorganization	-0.007	0.083	0.26	8	-0.3	15	23
SRC	0.02	0.004	-10000	0	-10000	0	0
PLEKHA2	-0.017	0.007	-10000	0	-10000	0	0
RAC1	0.019	0.007	-10000	0	-10000	0	0
PTEN	0.019	0.014	-10000	0	-10000	0	0
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
ARF6/GTP	-0.022	0.046	0.28	1	-10000	0	1
RhoA/GTP	-0.019	0.048	0.24	3	-10000	0	3
Src family/SYK family/BLNK-LAT	-0.015	0.11	-10000	0	-0.32	39	39
BLK	0.064	0.11	0.32	80	-0.33	1	81
PDPK1	0.021	0.003	-10000	0	-10000	0	0
CYTH1	-0.019	0.047	0.28	3	-10000	0	3
HCK	0.005	0.07	-10000	0	-0.33	22	22
CYTH3	-0.017	0.047	0.25	4	-10000	0	4
CYTH2	-0.019	0.048	0.25	4	-10000	0	4
KRAS	0.019	0.007	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	-0.001	0.049	-10000	0	-0.32	7	7
SGK1	-0.014	0.096	-10000	0	-0.33	38	38
INPP5D	0.019	0.027	-10000	0	-0.33	3	3
mol:GDP	-0.013	0.092	0.18	3	-0.29	32	35
SOS1	0.021	0.003	-10000	0	-10000	0	0
SYK	0.019	0.022	-10000	0	-0.33	2	2
ARF6/GDP	-0.012	0.06	0.22	5	-0.25	3	8
mol:PI-3-4-5-P3	-0.017	0.043	0.22	2	-10000	0	2
ARAP3/RAP1A/GTP	-0.016	0.047	0.16	32	-10000	0	32
VAV1	0.018	0.027	-10000	0	-0.33	3	3
mol:PI-3-4-P2	-0.017	0.014	-10000	0	-0.23	2	2
RAS family/GTP/PI3K Class I	-0.022	0.034	0.19	2	-10000	0	2
PLEKHA1	-0.02	0.012	-10000	0	-0.2	2	2
Rac1/GDP	-0.003	0.087	-10000	0	-0.31	24	24
LAT	0.021	0.014	0.32	1	-10000	0	1
Rac1/GTP	-0.005	0.097	0.21	1	-0.37	25	26
ITK	-0.023	0.045	0.21	2	-10000	0	2
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.023	0.091	0.22	6	-0.29	25	31
LCK	0.02	0.026	0.32	1	-0.33	2	3
BTK	-0.028	0.055	0.27	2	-0.28	2	4

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0	0.08	0.27	2	-0.3	22	24
PDGFB-D/PDGFRB/SLAP	0.022	0.034	-10000	0	-0.23	8	8
PDGFB-D/PDGFRB/APS/CBL	0.038	0.018	-10000	0	-0.2	1	1
AKT1	-0.012	0.077	0.34	12	-10000	0	12
mol:PI-4-5-P2	0	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.004	0.096	0.27	6	-0.35	22	28
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
FGR	-0.031	0.15	0.32	2	-0.48	43	45
mol:Ca2+	-0.005	0.1	0.26	7	-0.38	26	33
MYC	0.033	0.13	0.37	17	-0.49	6	23
SHC1	0.018	0.016	0.32	1	-10000	0	1
HRAS/GDP	-0.013	0.04	0.16	26	-10000	0	26
LRP1/PDGFRB/PDGFB	0.036	0.03	-10000	0	-0.19	7	7
GRB10	0.019	0.006	-10000	0	-10000	0	0
PTPN11	0.021	0.004	-10000	0	-10000	0	0
GO:0007205	-0.005	0.11	0.27	6	-0.39	26	32
PTEN	0.021	0.003	-10000	0	-10000	0	0
GRB2	0.02	0.004	-10000	0	-10000	0	0
GRB7	0.019	0.022	-10000	0	-0.33	2	2
PDGFB-D/PDGFRB/SHP2	0.03	0.009	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB10	0.027	0.011	-10000	0	-10000	0	0
cell cycle arrest	0.022	0.034	-10000	0	-0.23	8	8
HRAS	0.021	0.004	-10000	0	-10000	0	0
HIF1A	-0.016	0.072	0.32	12	-10000	0	12
GAB1	-0.003	0.1	0.29	4	-0.34	26	30
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	-0.002	0.087	0.27	9	-0.31	16	25
PDGFB-D/PDGFRB	0.038	0.016	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.03	0.008	-10000	0	-10000	0	0
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.006	0.059	-10000	0	-0.27	9	9
positive regulation of MAPKKK cascade	0.029	0.009	-10000	0	-10000	0	0
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
mol:IP3	-0.005	0.11	0.27	6	-0.39	26	32
E5	0	0.001	-10000	0	-10000	0	0
CSK	0.019	0.009	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7	0.029	0.019	-10000	0	-0.23	2	2
SHB	0.02	0.006	-10000	0	-10000	0	0
BLK	-0.028	0.17	0.32	3	-0.4	75	78
PTPN2	0.019	0.01	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.03	0.009	-10000	0	-10000	0	0
BCAR1	0.02	0.016	-10000	0	-0.33	1	1
VAV2	-0.005	0.11	0.28	6	-0.38	25	31
CBL	0.02	0.005	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.03	0.008	-10000	0	-10000	0	0
LCK	0.006	0.059	0.32	2	-0.42	4	6
PDGFRB	0.02	0.009	-10000	0	-10000	0	0
ACP1	0.021	0.002	-10000	0	-10000	0	0
HCK	-0.018	0.14	0.33	2	-0.55	27	29
ABL1	-0.007	0.1	0.25	8	-0.34	27	35
PDGFB-D/PDGFRB/CBL	-0.006	0.12	0.31	3	-0.4	28	31
PTPN1	0.019	0.009	-10000	0	-10000	0	0
SNX15	0.021	0.004	-10000	0	-10000	0	0
STAT3	0.021	0.003	-10000	0	-10000	0	0
STAT1	0.021	0.002	-10000	0	-10000	0	0
cell proliferation	0.033	0.12	0.36	18	-0.41	8	26
SLA	0.012	0.046	-10000	0	-0.33	9	9
actin cytoskeleton reorganization	-0.014	0.058	0.32	5	-10000	0	5
SRC	0	0.091	0.32	2	-0.59	9	11
PI3K	-0.032	0.02	-10000	0	-0.17	6	6
PDGFB-D/PDGFRB/GRB7/SHC	0.033	0.023	-10000	0	-0.2	2	2
SH2B2	0.02	0.016	-10000	0	-0.33	1	1
PLCgamma1/SPHK1	0.004	0.098	0.27	6	-0.36	22	28
LYN	0.005	0.053	0.31	1	-0.41	3	4
LRP1	0.018	0.031	-10000	0	-0.33	4	4
SOS1	0.021	0.003	-10000	0	-10000	0	0
STAT5B	0.021	0.003	-10000	0	-10000	0	0
STAT5A	0.02	0.016	-10000	0	-0.33	1	1
NCK1-2/p130 Cas	0.052	0.03	-10000	0	-0.17	1	1
SPHK1	0.023	0.031	0.32	5	-10000	0	5
EDG1	0	0.002	-10000	0	-10000	0	0
mol:DAG	-0.005	0.11	0.27	6	-0.39	26	32
PLCG1	-0.006	0.11	0.28	6	-0.4	26	32
NHERF/PDGFRB	0.037	0.028	0.22	1	-0.2	5	6
YES1	-0.011	0.12	0.34	1	-0.58	18	19
cell migration	0.037	0.028	0.22	1	-0.2	5	6
SHC/Grb2/SOS1	0.046	0.032	-10000	0	-10000	0	0
SLC9A3R2	0.017	0.034	-10000	0	-0.33	5	5
SLC9A3R1	0.021	0.014	0.32	1	-10000	0	1
NHERF1-2/PDGFRB/PTEN	0.047	0.03	0.23	1	-0.18	5	6
FYN	-0.028	0.13	0.32	2	-0.42	45	47
DOK1	-0.011	0.04	0.16	25	-10000	0	25
HRAS/GTP	0.015	0.003	-10000	0	-10000	0	0
PDGFB	0.017	0.031	-10000	0	-0.33	4	4
RAC1	0.01	0.12	0.32	13	-0.39	18	31
PRKCD	-0.01	0.042	0.17	27	-10000	0	27
FER	-0.011	0.042	0.17	26	-10000	0	26
MAPKKK cascade	0.015	0.1	0.35	22	-10000	0	22
RASA1	-0.011	0.041	0.17	25	-10000	0	25
NCK1	0.021	0.003	-10000	0	-10000	0	0
NCK2	0.021	0.002	-10000	0	-10000	0	0
p62DOK/Csk	-0.015	0.041	0.16	26	-10000	0	26
PDGFB-D/PDGFRB/SHB	0.029	0.01	-10000	0	-10000	0	0
chemotaxis	-0.006	0.1	0.24	8	-0.33	27	35
STAT1-3-5/STAT1-3-5	0.043	0.026	-10000	0	-0.18	1	1
Bovine Papilomavirus E5/PDGFRB	0.015	0.006	-10000	0	-10000	0	0
PTPRJ	0.021	0.003	-10000	0	-10000	0	0

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.016	0.016	-10000	0	-10000	0	0
HSPA8	0.019	0.008	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	0.025	0.06	0.23	7	-0.22	8	15
AKT1	0.013	0.028	-10000	0	-0.11	2	2
GSC	0.038	0.12	0.41	14	-0.41	7	21
NKX2-5	0	0	-10000	0	-10000	0	0
muscle cell differentiation	-0.011	0.076	0.28	4	-10000	0	4
SMAD2-3/SMAD4/SP1	0.047	0.064	-10000	0	-0.25	1	1
SMAD4	0.016	0.031	-10000	0	-0.17	1	1
CBFB	0.02	0.004	-10000	0	-10000	0	0
SAP18	0.02	0.005	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.025	0.06	0.23	7	-0.2	24	31
SMAD3/SMAD4/VDR	0.043	0.049	-10000	0	-0.23	1	1
MYC	0.019	0.026	-10000	0	-0.33	2	2
CDKN2B	-0.17	0.4	-10000	0	-1.1	58	58
AP1	0.007	0.057	-10000	0	-0.25	9	9
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	-0.021	0.096	-10000	0	-0.32	31	31
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.022	0.099	-10000	0	-0.33	35	35
SP3	0.021	0.003	-10000	0	-10000	0	0
CREB1	0.021	0.003	-10000	0	-10000	0	0
FOXH1	0.052	0.093	0.33	51	-10000	0	51
SMAD3/SMAD4/GR	0.03	0.042	-10000	0	-10000	0	0
GATA3	0.02	0.025	0.32	1	-0.32	1	2
SKI/SIN3/HDAC complex/NCoR1	-0.013	0.073	-10000	0	-0.34	15	15
MEF2C/TIF2	0.007	0.061	0.29	3	-0.23	1	4
endothelial cell migration	-0.013	0.077	0.71	4	-10000	0	4
MAX	0.02	0.009	-10000	0	-10000	0	0
RBBP7	0.021	0.004	-10000	0	-10000	0	0
RBBP4	0.021	0.003	-10000	0	-10000	0	0
RUNX2	0.025	0.035	0.32	7	-10000	0	7
RUNX3	0.019	0.027	-10000	0	-0.33	3	3
RUNX1	0.02	0.005	-10000	0	-10000	0	0
CTBP1	0.02	0.004	-10000	0	-10000	0	0
NR3C1	0.019	0.009	-10000	0	-10000	0	0
VDR	0.021	0.021	0.32	1	-0.33	1	2
CDKN1A	-0.001	0.052	-10000	0	-0.84	1	1
KAT2B	0.017	0.013	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	0.059	0.076	0.25	42	-10000	0	42
DCP1A	0.021	0.004	-10000	0	-10000	0	0
SKI	0.021	0.004	-10000	0	-10000	0	0
SERPINE1	0.013	0.077	-10000	0	-0.72	4	4
SMAD3/SMAD4/ATF2	0.031	0.041	-10000	0	-0.18	1	1
SMAD3/SMAD4/ATF3	0.021	0.059	-10000	0	-0.21	18	18
SAP30	0.021	0.004	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.029	0.03	-10000	0	-10000	0	0
JUN	-0.008	0.055	0.22	1	-0.25	9	10
SMAD3/SMAD4/IRF7	0.034	0.047	0.35	2	-10000	0	2
TFE3	0.022	0.007	-10000	0	-10000	0	0
COL1A2	0.019	0.075	0.31	18	-0.51	4	22
mesenchymal cell differentiation	-0.033	0.045	0.18	1	-0.23	5	6
DLX1	0.038	0.071	0.32	30	-10000	0	30
TCF3	0.02	0.006	-10000	0	-10000	0	0
FOS	-0.002	0.079	-10000	0	-0.34	26	26
SMAD3/SMAD4/Max	0.03	0.042	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.034	0.024	-10000	0	-10000	0	0
ZBTB17	0.022	0.009	-10000	0	-10000	0	0
LAMC1	-0.012	0.031	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.031	0.041	-10000	0	-0.18	1	1
IRF7	0.023	0.025	0.34	3	-10000	0	3
ESR1	0.016	0.061	0.32	9	-0.33	8	17
HNF4A	0.07	0.13	0.32	97	-0.33	10	107
MEF2C	0.021	0.077	0.24	27	-10000	0	27
SMAD2-3/SMAD4	0.034	0.053	-10000	0	-0.24	1	1
Cbp/p300/Src-1	0.034	0.026	-10000	0	-10000	0	0
IGHV3OR16-13	0.004	0.016	-10000	0	-0.32	1	1
TGIF2/HDAC complex	0.02	0.004	-10000	0	-10000	0	0
CREBBP	0.017	0.015	-10000	0	-10000	0	0
SKIL	0.02	0.005	-10000	0	-10000	0	0
HDAC1	0.021	0.003	-10000	0	-10000	0	0
HDAC2	0.019	0.006	-10000	0	-10000	0	0
SNIP1	0.02	0.006	-10000	0	-10000	0	0
GCN5L2	0	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.035	0.042	-10000	0	-10000	0	0
MSG1/HSC70	0.021	0.061	0.23	8	-0.23	24	32
SMAD2	0.018	0.027	-10000	0	-10000	0	0
SMAD3	0.009	0.033	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.002	0.046	-10000	0	-0.22	4	4
SMAD2/SMAD2/SMAD4	-0.008	0.077	0.21	3	-0.3	17	20
NCOR1	0.02	0.006	-10000	0	-10000	0	0
NCOA2	0.016	0.035	-10000	0	-0.33	5	5
NCOA1	0.021	0.002	-10000	0	-10000	0	0
MYOD/E2A	0.027	0.012	0.23	1	-10000	0	1
SMAD2-3/SMAD4/SP1/MIZ-1	0.052	0.068	-10000	0	-0.27	1	1
IFNB1	-0.013	0.035	0.33	3	-10000	0	3
SMAD3/SMAD4/MEF2C	0.048	0.066	0.25	4	-10000	0	4
CITED1	0.009	0.083	0.32	8	-0.33	24	32
SMAD2-3/SMAD4/ARC105	0.043	0.053	-10000	0	-0.21	1	1
RBL1	0.02	0.004	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.042	0.15	-10000	0	-0.52	39	39
RUNX1-3/PEBPB2	0.038	0.021	-10000	0	-0.18	3	3
SMAD7	0	0.077	-10000	0	-0.44	5	5
MYC/MIZ-1	0.028	0.025	0.18	2	-0.23	1	3
SMAD3/SMAD4	-0.004	0.065	0.24	1	-0.32	3	4
IL10	-0.015	0.051	0.3	3	-0.33	6	9
PIASy/HDAC complex	0.018	0.013	-10000	0	-10000	0	0
PIAS3	0.015	0.013	-10000	0	-10000	0	0
CDK2	0.017	0.014	-10000	0	-10000	0	0
IL5	-0.016	0.034	-10000	0	-0.25	1	1
CDK4	0.016	0.015	-10000	0	-10000	0	0
PIAS4	0.018	0.013	-10000	0	-10000	0	0
ATF3	0.007	0.064	-10000	0	-0.33	18	18
SMAD3/SMAD4/SP1	0.036	0.051	-10000	0	-0.2	1	1
FOXG1	0.046	0.09	0.32	49	-10000	0	49
FOXO3	-0.019	0.023	-10000	0	-0.14	2	2
FOXO1	-0.021	0.024	-10000	0	-0.14	1	1
FOXO4	-0.021	0.023	-10000	0	-0.14	1	1
heart looping	0.021	0.077	0.24	27	-10000	0	27
CEBPB	0.014	0.021	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	0.041	0.056	0.24	19	-0.18	1	20
MYOD1	0.019	0.024	0.32	3	-10000	0	3
SMAD3/SMAD4/HNF4	0.057	0.091	0.24	76	-0.2	11	87
SMAD3/SMAD4/GATA3	0.031	0.049	-10000	0	-0.23	3	3
SnoN/SIN3/HDAC complex/NCoR1	0.02	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.045	0.048	-10000	0	-0.21	1	1
SMAD3/SMAD4/SP1-3	0.045	0.053	-10000	0	-10000	0	0
MED15	0.02	0.005	-10000	0	-10000	0	0
SP1	0.019	0.021	-10000	0	-10000	0	0
SIN3B	0.02	0.005	-10000	0	-10000	0	0
SIN3A	0.021	0.004	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.057	0.072	0.24	40	-10000	0	40
ITGB5	-0.014	0.044	0.26	2	-10000	0	2
TGIF/SIN3/HDAC complex/CtBP	-0.011	0.061	-10000	0	-0.31	11	11
SMAD3/SMAD4/AR	0.001	0.091	-10000	0	-0.22	64	64
AR	-0.025	0.12	0.32	1	-0.33	69	70
negative regulation of cell growth	-0.005	0.066	-10000	0	-0.26	16	16
SMAD3/SMAD4/MYOD	0.03	0.043	0.24	2	-0.18	1	3
E2F5	0.019	0.007	-10000	0	-10000	0	0
E2F4	0.02	0.004	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.071	0.074	0.29	8	-10000	0	8
SMAD2-3/SMAD4/FOXO1-3a-4	-0.02	0.1	-10000	0	-0.37	35	35
TFDP1	0.02	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.024	0.064	-10000	0	-0.25	8	8
SMAD3/SMAD4/RUNX2	0.033	0.046	0.24	5	-0.18	1	6
TGIF2	0.02	0.004	-10000	0	-10000	0	0
TGIF1	0.02	0.006	-10000	0	-10000	0	0
ATF2	0.021	0.003	-10000	0	-10000	0	0

Ephrin A reverse signaling

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
MAPKKK cascade	0.028	0.03	0.21	10	-0.17	3	13
EFNA5	0.019	0.033	0.32	2	-0.33	3	5
FYN	-0.012	0.029	0.18	9	-0.18	2	11
neuron projection morphogenesis	0.028	0.03	0.21	10	-0.17	3	13
cell-cell signaling	0	0	-10000	0	-10000	0	0
Ephrin A5/EPHA5	0.028	0.031	0.21	10	-0.17	3	13
EPHA5	0.025	0.04	0.32	9	-10000	0	9

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.019	0.007	-10000	0	-10000	0	0
Caspase 8 (4 units)	0.02	0.048	-10000	0	-0.28	3	3
NEF	-0.001	0.018	-10000	0	-0.17	6	6
NFKBIA	0.019	0.009	-10000	0	-10000	0	0
BIRC3	0.006	0.068	0.18	65	-10000	0	65
CYCS	0.003	0.044	0.16	27	-0.29	2	29
RIPK1	0.021	0.004	-10000	0	-10000	0	0
CD247	0.018	0.026	-10000	0	-0.22	5	5
MAP2K7	-0.016	0.17	-10000	0	-0.64	31	31
protein ubiquitination	0.002	0.065	0.23	5	-0.25	9	14
CRADD	0.021	0.021	0.32	1	-0.33	1	2
DAXX	0.021	0.004	-10000	0	-10000	0	0
FAS	0.017	0.037	-10000	0	-0.33	6	6
BID	0.007	0.049	0.16	29	-0.25	4	33
NF-kappa-B/RelA/I kappa B alpha	0.039	0.025	0.22	5	-10000	0	5
TRADD	0.02	0.004	-10000	0	-10000	0	0
MAP3K5	0.019	0.006	-10000	0	-10000	0	0
CFLAR	0.021	0.002	-10000	0	-10000	0	0
FADD	0.02	0.004	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.039	0.025	0.22	5	-10000	0	5
MAPK8	-0.017	0.16	0.38	1	-0.6	31	32
APAF1	0.021	0.003	-10000	0	-10000	0	0
TRAF1	0.021	0.004	-10000	0	-10000	0	0
TRAF2	0.021	0.004	-10000	0	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.008	0.034	-10000	0	-0.25	5	5
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.002	0.066	-10000	0	-0.31	9	9
CHUK	0.001	0.068	0.23	5	-0.27	9	14
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.05	0.032	-10000	0	-0.17	3	3
TCRz/NEF	0.014	0.025	-10000	0	-0.23	5	5
TNF	0.011	0.06	0.32	1	-0.33	15	16
FASLG	-0.014	0.034	-10000	0	-0.34	5	5
NFKB1	0.021	0.011	-10000	0	-0.13	2	2
TNFR1A/BAG4/TNF-alpha	0.029	0.042	0.22	1	-0.19	14	15
CASP6	0.028	0.071	-10000	0	-0.48	4	4
CASP7	0.026	0.094	0.31	20	-0.3	2	22
RELA	0.021	0.011	-10000	0	-0.13	2	2
CASP2	0.02	0.004	-10000	0	-10000	0	0
CASP3	0.024	0.091	0.32	17	-0.29	1	18
TNFRSF1A	0.02	0.005	-10000	0	-10000	0	0
TNFR1A/BAG4	0.026	0.012	-10000	0	-10000	0	0
CASP8	0.02	0.016	-10000	0	-0.33	1	1
CASP9	0.021	0.004	-10000	0	-10000	0	0
MAP3K14	0.004	0.066	0.2	3	-0.3	8	11
APAF-1/Caspase 9	-0.01	0.053	0.22	5	-0.28	1	6
BCL2	-0.016	0.15	0.36	2	-0.54	31	33

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	0.009	0.027	-10000	0	-0.18	9	9
epithelial cell differentiation	0.041	0.018	-10000	0	-0.16	2	2
CYFIP2	0.016	0.04	-10000	0	-0.33	7	7
ENAH	-0.018	0.057	0.29	5	-0.23	1	6
EGFR	0.014	0.045	0.32	1	-0.33	8	9
EPHA2	0.014	0.048	-10000	0	-0.33	10	10
MYO6	-0.018	0.038	0.22	9	-10000	0	9
CTNNB1	0.021	0.004	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.038	0.022	-10000	0	-0.2	3	3
AQP5	-0.06	0.17	0.46	3	-0.38	98	101
CTNND1	0.021	0.003	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.018	0.039	0.22	10	-10000	0	10
regulation of calcium-dependent cell-cell adhesion	-0.087	0.075	0.16	3	-0.3	1	4
EGF	0.071	0.12	0.32	91	-0.33	5	96
NCKAP1	0.021	0.003	-10000	0	-10000	0	0
AQP3	-0.021	0.072	0.24	1	-0.32	25	26
cortical microtubule organization	0.041	0.018	-10000	0	-0.16	2	2
GO:0000145	-0.018	0.037	0.2	10	-10000	0	10
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.045	0.02	-10000	0	-0.16	2	2
MLLT4	0.019	0.006	-10000	0	-10000	0	0
ARF6/GDP	-0.032	0.023	-10000	0	-0.17	5	5
ARF6	0.02	0.004	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.04	0.034	-10000	0	-0.18	7	7
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.01	0.038	0.42	2	-0.21	1	3
PVRL2	0.02	0.004	-10000	0	-10000	0	0
ZYX	-0.019	0.04	0.43	2	-10000	0	2
ARF6/GTP	0.044	0.035	-10000	0	-0.17	6	6
CDH1	0.019	0.022	-10000	0	-0.33	2	2
EGFR/EGFR/EGF/EGF	0.041	0.055	0.24	1	-0.18	11	12
RhoA/GDP	0.042	0.019	-10000	0	-0.16	2	2
actin cytoskeleton organization	-0.02	0.036	0.21	9	-10000	0	9
IGF-1R heterotetramer	0.02	0.004	-10000	0	-10000	0	0
GIT1	0.021	0.004	-10000	0	-10000	0	0
IGF1R	0.02	0.004	-10000	0	-10000	0	0
IGF1	0.014	0.052	0.32	1	-0.33	11	12
DIAPH1	0.015	0.12	-10000	0	-0.55	13	13
Wnt receptor signaling pathway	-0.041	0.018	0.16	2	-10000	0	2
RHOA	0.02	0.004	-10000	0	-10000	0	0
RhoA/GTP	-0.033	0.025	-10000	0	-0.18	6	6
CTNNA1	0.02	0.004	-10000	0	-10000	0	0
VCL	-0.02	0.037	0.21	9	-10000	0	9
EFNA1	0.017	0.017	-10000	0	-0.33	1	1
LPP	-0.021	0.038	0.21	10	-10000	0	10
Ephrin A1/EPHA2	0.027	0.034	-10000	0	-0.18	9	9
SEC6/SEC8	-0.025	0.018	-10000	0	-10000	0	0
MGAT3	-0.088	0.076	0.16	3	-0.3	1	4
HGF/MET	0.021	0.057	-10000	0	-0.17	35	35
HGF	0.006	0.079	0.32	4	-0.33	24	28
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.009	0.027	-10000	0	-0.18	9	9
actin cable formation	0.009	0.085	0.29	18	-0.25	3	21
KIAA1543	-0.02	0.028	0.18	8	-10000	0	8
KIFC3	-0.023	0.02	0.16	3	-10000	0	3
NCK1	0.021	0.003	-10000	0	-10000	0	0
EXOC3	0.016	0.009	-10000	0	-10000	0	0
ACTN1	-0.019	0.038	0.22	10	-10000	0	10
NCK1/GIT1	0.03	0.007	-10000	0	-10000	0	0
mol:GDP	0.041	0.018	-10000	0	-0.16	2	2
EXOC4	0.02	0.005	-10000	0	-10000	0	0
STX4	-0.02	0.03	0.19	8	-10000	0	8
PIP5K1C	-0.019	0.039	0.22	10	-10000	0	10
LIMA1	0.021	0.003	-10000	0	-10000	0	0
ABI1	0.021	0.004	-10000	0	-10000	0	0
ROCK1	-0.006	0.078	0.31	11	-0.26	1	12
adherens junction assembly	-0.025	0.087	0.35	6	-0.44	9	15
IGF-1R heterotetramer/IGF1	0.031	0.034	-10000	0	-0.16	12	12
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.028	0.011	-10000	0	-10000	0	0
MET	0.011	0.072	0.32	6	-0.33	18	24
PLEKHA7	-0.02	0.029	0.19	8	-10000	0	8
mol:GTP	0.039	0.034	-10000	0	-0.18	7	7
establishment of epithelial cell apical/basal polarity	0.018	0.095	0.31	17	-10000	0	17
cortical actin cytoskeleton stabilization	0.009	0.027	-10000	0	-0.18	9	9
regulation of cell-cell adhesion	-0.02	0.036	0.21	9	-10000	0	9
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.009	0.027	-10000	0	-0.18	9	9

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	0.027	0.045	-10000	0	-0.16	21	21
TC10/GTP	0.023	0.043	-10000	0	-0.16	20	20
Insulin Receptor/Insulin/IRS1/Shp2	0.049	0.02	-10000	0	-0.15	1	1
HRAS	0.021	0.004	-10000	0	-10000	0	0
APS homodimer	0.019	0.016	-10000	0	-0.32	1	1
GRB14	0.034	0.078	0.32	28	-0.33	5	33
FOXO3	-0.049	0.2	-10000	0	-0.62	53	53
AKT1	-0.02	0.052	0.28	5	-10000	0	5
INSR	0.022	0.007	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.041	0.03	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.019	0.006	-10000	0	-10000	0	0
SORBS1	0.002	0.079	-10000	0	-0.33	28	28
CRK	0.019	0.006	-10000	0	-10000	0	0
PTPN1	-0.013	0.019	-10000	0	-10000	0	0
CAV1	-0.098	0.08	-10000	0	-0.17	268	268
CBL/APS/CAP/Crk-II/C3G	0.041	0.052	-10000	0	-0.17	21	21
Insulin Receptor/Insulin/IRS1/NCK2	0.05	0.019	-10000	0	-0.15	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.037	0.02	-10000	0	-0.17	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.001	0.07	-10000	0	-0.32	18	18
RPS6KB1	-0.023	0.048	0.27	5	-10000	0	5
PARD6A	0.02	0.016	-10000	0	-0.33	1	1
CBL	0.02	0.005	-10000	0	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.012	0.037	-10000	0	-0.57	2	2
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.026	0.042	0.16	1	-10000	0	1
HRAS/GTP	-0.028	0.019	-10000	0	-0.16	2	2
Insulin Receptor	0.022	0.007	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.049	0.029	-10000	0	-10000	0	0
PRKCI	0.003	0.075	-10000	0	-0.33	4	4
Insulin Receptor/Insulin/GRB14/PDK1	-0.023	0.033	0.1	1	-0.17	4	5
SHC1	0.018	0.016	0.32	1	-10000	0	1
negative regulation of MAPKKK cascade	0.029	0.039	-10000	0	-0.48	2	2
PI3K	0.046	0.024	-10000	0	-0.17	1	1
NCK2	0.021	0.002	-10000	0	-10000	0	0
RHOQ	0.021	0.003	-10000	0	-10000	0	0
mol:H2O2	-0.002	0.003	-10000	0	-10000	0	0
HRAS/GDP	0.015	0.003	-10000	0	-10000	0	0
AKT2	-0.02	0.052	0.29	5	-10000	0	5
PRKCZ	-0.003	0.086	-10000	0	-0.39	6	6
SH2B2	0.02	0.016	-10000	0	-0.33	1	1
SHC/SHIP	-0.018	0.024	0.18	2	-10000	0	2
F2RL2	0.036	0.079	0.32	31	-0.33	4	35
TRIP10	0.02	0.005	-10000	0	-10000	0	0
Insulin Receptor/Insulin/Shc	0.032	0.018	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.027	0.008	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.049	0.029	-10000	0	-10000	0	0
RAPGEF1	0.021	0.004	-10000	0	-10000	0	0
RASA1	0.02	0.005	-10000	0	-10000	0	0
NCK1	0.021	0.003	-10000	0	-10000	0	0
CBL/APS/CAP/Crk-II	0.034	0.051	-10000	0	-0.18	23	23
TC10/GDP	0.016	0.002	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.04	0.025	-10000	0	-10000	0	0
INPP5D	-0.019	0.019	0.15	2	-0.17	2	4
SOS1	0.021	0.003	-10000	0	-10000	0	0
SGK1	-0.052	0.2	-10000	0	-0.66	48	48
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.021	0.004	-10000	0	-10000	0	0
IRS1	0.02	0.016	-10000	0	-0.33	1	1
p62DOK/RasGAP	0.029	0.04	-10000	0	-0.49	2	2
INS	-0.014	0.014	-10000	0	-10000	0	0
mol:PI-3-4-P2	-0.019	0.019	0.15	2	-0.17	2	4
GRB2	0.02	0.004	-10000	0	-10000	0	0
EIF4EBP1	-0.018	0.052	0.22	9	-10000	0	9
PTPRA	0.022	0.006	-10000	0	-10000	0	0
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
TC10/GTP/CIP4	0.027	0.008	-10000	0	-10000	0	0
PDPK1	0.021	0.003	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.009	0.023	-10000	0	-0.19	1	1
Insulin Receptor/Insulin/IRS1	0.037	0.016	-10000	0	-0.14	1	1
Insulin Receptor/Insulin/IRS3	0.029	0.012	-10000	0	-10000	0	0
Par3/Par6	0.051	0.045	0.21	26	-0.16	4	30

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.018	0.006	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP1	-0.011	0.003	-10000	0	-10000	0	0
mol:DAG	-0.014	0.033	0.27	3	-10000	0	3
VEGFR1 homodimer/NRP1/VEGFR 121	0.017	0.006	-10000	0	-10000	0	0
CaM/Ca2+	-0.018	0.027	0.22	1	-10000	0	1
HIF1A	0.022	0.004	-10000	0	-10000	0	0
GAB1	0.02	0.022	-10000	0	-0.33	2	2
AKT1	-0.015	0.044	0.46	2	-10000	0	2
PLCG1	-0.014	0.033	0.27	3	-10000	0	3
NOS3	-0.007	0.083	0.44	6	-0.43	4	10
CBL	0.02	0.005	-10000	0	-10000	0	0
mol:NO	-0.004	0.094	0.48	8	-0.42	5	13
FLT1	-0.014	0.004	-10000	0	-10000	0	0
PGF	0.029	0.051	0.32	15	-10000	0	15
VEGFR1 homodimer/NRP2/VEGFR121	0.028	0.016	-10000	0	-10000	0	0
CALM1	0.02	0.005	-10000	0	-10000	0	0
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
eNOS/Hsp90	-0.013	0.082	0.35	4	-0.43	7	11
endothelial cell proliferation	-0.007	0.055	0.32	6	-10000	0	6
mol:Ca2+	-0.014	0.033	0.27	3	-10000	0	3
MAPK3	-0.019	0.041	0.28	7	-10000	0	7
MAPK1	-0.02	0.037	0.34	4	-10000	0	4
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
PLGF homodimer	0.029	0.051	0.32	15	-10000	0	15
PRKACA	0.02	0.005	-10000	0	-10000	0	0
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	-0.19	0.17	-10000	0	-0.33	311	311
VEGFA homodimer	0.02	0.004	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0.018	0.006	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	-0.022	0.039	0.3	5	-10000	0	5
PI3K	0.042	0.035	-10000	0	-10000	0	0
PRKCA	-0.018	0.029	0.23	4	-10000	0	4
PRKCB	-0.02	0.037	0.22	6	-10000	0	6
VEGFR1 homodimer/PLGF homodimer	0.024	0.035	0.22	15	-10000	0	15
VEGFA	0.021	0.004	-10000	0	-10000	0	0
VEGFB	0.021	0.003	-10000	0	-10000	0	0
mol:IP3	-0.014	0.033	0.27	3	-10000	0	3
RASA1	-0.017	0.025	0.18	8	-10000	0	8
NRP2	0.019	0.027	-10000	0	-0.33	3	3
VEGFR1 homodimer	-0.014	0.004	-10000	0	-10000	0	0
VEGFB homodimer	0.021	0.003	-10000	0	-10000	0	0
NCK1	0.021	0.003	-10000	0	-10000	0	0
eNOS/Caveolin-1	-0.091	0.11	0.44	2	-0.4	22	24
PTPN11	0.021	0.004	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.041	0.034	-10000	0	-10000	0	0
mol:L-citrulline	-0.004	0.094	0.48	8	-0.42	5	13
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.038	0.017	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.029	0.011	-10000	0	-10000	0	0
CD2AP	0.02	0.004	-10000	0	-10000	0	0
PI3K/GAB1	0.049	0.04	-10000	0	-10000	0	0
PDPK1	-0.016	0.048	0.39	3	-10000	0	3
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.029	0.011	-10000	0	-10000	0	0
mol:NADP	-0.004	0.094	0.48	8	-0.42	5	13
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.037	0.017	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP2	0.018	0.015	-10000	0	-10000	0	0

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.02	0.015	-10000	0	-0.33	1	1
ANTXR2	0.021	0.003	-10000	0	-10000	0	0
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.003	0.002	-10000	0	-0.046	1	1
monocyte activation	-0.01	0.098	-10000	0	-0.36	34	34
MAP2K2	-0.029	0.15	-10000	0	-0.57	36	36
MAP2K1	-0.008	0.002	-10000	0	-10000	0	0
MAP2K7	-0.007	0.002	-10000	0	-10000	0	0
MAP2K6	-0.006	0.016	0.062	15	-0.16	2	17
CYAA	-0.011	0.007	-10000	0	-0.16	1	1
MAP2K4	-0.007	0.002	-10000	0	-10000	0	0
IL1B	-0.014	0.036	0.14	4	-0.16	25	29
Channel	0.026	0.01	-10000	0	-0.17	1	1
NLRP1	-0.007	0.007	-10000	0	-0.16	1	1
CALM1	0.02	0.005	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.002	0.06	-10000	0	-0.39	12	12
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.003	0.002	0.046	1	-10000	0	1
MAPK3	-0.008	0.002	-10000	0	-10000	0	0
MAPK1	-0.007	0.002	-10000	0	-10000	0	0
PGR	-0.032	0.056	-10000	0	-0.16	84	84
PA/Cellular Receptors	0.028	0.011	-10000	0	-0.19	1	1
apoptosis	-0.003	0.002	-10000	0	-0.046	1	1
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.026	0.009	-10000	0	-0.16	1	1
macrophage activation	-0.011	0.003	-10000	0	-10000	0	0
TNF	0.011	0.06	0.32	1	-0.33	15	16
VCAM1	-0.009	0.096	-10000	0	-0.37	31	31
platelet activation	-0.002	0.06	-10000	0	-0.39	12	12
MAPKKK cascade	0.004	0.017	-10000	0	-0.093	5	5
IL18	-0.009	0.024	0.14	2	-0.21	5	7
negative regulation of macrophage activation	-0.003	0.002	-10000	0	-0.046	1	1
LEF	-0.003	0.002	-10000	0	-0.046	1	1
CASP1	-0.004	0.011	-10000	0	-0.12	4	4
mol:cAMP	-0.002	0.06	-10000	0	-0.39	12	12
necrosis	-0.003	0.002	-10000	0	-0.046	1	1
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.026	0.009	-10000	0	-0.16	1	1
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.021	0.003	-10000	0	-10000	0	0
HDAC2	0.02	0.006	-10000	0	-10000	0	0
GNB1/GNG2	0.036	0.025	0.22	1	-0.2	3	4
forebrain development	-0.037	0.14	-10000	0	-0.52	25	25
GNAO1	0.015	0.038	0.32	4	-0.33	2	6
SMO/beta Arrestin2	0.021	0.029	0.23	3	-0.2	1	4
SMO	0.014	0.033	0.32	3	-0.33	1	4
ARRB2	0.013	0.015	-10000	0	-10000	0	0
GLI3/SPOP	0.002	0.087	-10000	0	-0.36	16	16
mol:GTP	-0.001	0.002	-10000	0	-10000	0	0
GSK3B	0.021	0.003	-10000	0	-10000	0	0
GNAI2	0.014	0.015	-10000	0	-10000	0	0
SIN3/HDAC complex	0.048	0.02	-10000	0	-10000	0	0
GNAI1	0.014	0.021	-10000	0	-0.33	1	1
XPO1	0.013	0.02	-10000	0	-10000	0	0
GLI1/Su(fu)	-0.033	0.14	-10000	0	-0.52	22	22
SAP30	0.021	0.004	-10000	0	-10000	0	0
mol:GDP	0.014	0.033	0.32	3	-0.32	1	4
MIM/GLI2A	0.001	0.047	-10000	0	-0.33	1	1
IFT88	0.02	0.005	-10000	0	-10000	0	0
GNAI3	0.014	0.016	-10000	0	-10000	0	0
GLI2	-0.006	0.073	-10000	0	-0.38	12	12
GLI3	-0.009	0.088	-10000	0	-0.36	17	17
CSNK1D	0.021	0.004	-10000	0	-10000	0	0
CSNK1E	0.02	0.005	-10000	0	-10000	0	0
SAP18	0.02	0.005	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.02	0.005	-10000	0	-10000	0	0
GNG2	0.019	0.022	-10000	0	-0.33	2	2
Gi family/GTP	-0.014	0.067	-10000	0	-0.21	29	29
SIN3B	0.021	0.005	-10000	0	-10000	0	0
SIN3A	0.021	0.004	-10000	0	-10000	0	0
GLI3/Su(fu)	-0.007	0.088	-10000	0	-0.37	17	17
GLI2/Su(fu)	-0.006	0.086	-10000	0	-0.38	19	19
FOXA2	-0.14	0.34	-10000	0	-0.85	93	93
neural tube patterning	-0.037	0.14	-10000	0	-0.52	25	25
SPOP	0.021	0.004	-10000	0	-10000	0	0
Su(fu)/PIAS1	0.014	0.036	-10000	0	-10000	0	0
GNB1	0.021	0.004	-10000	0	-10000	0	0
CSNK1G2	0.02	0.006	-10000	0	-10000	0	0
CSNK1G3	0.02	0.005	-10000	0	-10000	0	0
MTSS1	0.001	0.047	-10000	0	-0.33	1	1
embryonic limb morphogenesis	-0.037	0.14	-10000	0	-0.52	25	25
SUFU	0.007	0.014	-10000	0	-10000	0	0
LGALS3	0.02	0.004	-10000	0	-10000	0	0
catabolic process	-0.003	0.12	-10000	0	-0.48	23	23
GLI3A/CBP	0.006	0.06	-10000	0	-0.32	14	14
KIF3A	0.02	0.005	-10000	0	-10000	0	0
GLI1	-0.038	0.15	-10000	0	-0.53	25	25
RAB23	0.02	0.005	-10000	0	-10000	0	0
CSNK1A1	0.02	0.005	-10000	0	-10000	0	0
IFT172	0.021	0.002	-10000	0	-10000	0	0
RBBP7	0.021	0.004	-10000	0	-10000	0	0
Su(fu)/Galectin3	0.013	0.038	-10000	0	-10000	0	0
GNAZ	-0.012	0.092	-10000	0	-0.33	39	39
RBBP4	0.021	0.003	-10000	0	-10000	0	0
CSNK1G1	0.021	0.004	-10000	0	-10000	0	0
PIAS1	0.021	0.004	-10000	0	-10000	0	0
PRKACA	0.02	0.005	-10000	0	-10000	0	0
GLI2/SPOP	0	0.086	-10000	0	-0.4	16	16
STK36	0.013	0.019	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.013	0.064	-10000	0	-0.29	8	8
PTCH1	-0.046	0.18	-10000	0	-0.84	17	17
MIM/GLI1	-0.051	0.19	-10000	0	-0.47	74	74
CREBBP	0.006	0.06	-10000	0	-0.32	14	14
Su(fu)/SIN3/HDAC complex	0.001	0.063	-10000	0	-0.32	10	10

mTOR 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
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.021	0.002	-10000	0	-10000	0	0
mol:PIP3	-0.013	0.025	-10000	0	-0.2	6	6
FRAP1	-0.006	0.081	-10000	0	-0.42	17	17
AKT1	-0.008	0.035	0.15	12	-0.24	4	16
INSR	0.02	0.005	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.024	0.007	-10000	0	-10000	0	0
mol:GTP	-0.012	0.044	0.25	1	-0.22	2	3
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.015	0.026	-10000	0	-0.2	5	5
TSC2	0.021	0.003	-10000	0	-10000	0	0
RHEB/GDP	-0.022	0.025	-10000	0	-0.19	2	2
TSC1	0.021	0.004	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.015	0.026	-10000	0	-0.21	6	6
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.013	0.036	-10000	0	-0.22	5	5
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.021	0.002	-10000	0	-10000	0	0
RPS6KB1	0.005	0.057	0.21	3	-0.36	5	8
MAP3K5	-0.012	0.054	0.18	4	-0.18	45	49
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
apoptosis	-0.012	0.054	0.18	4	-0.18	45	49
mol:LY294002	0	0	-10000	0	-0.001	2	2
EIF4B	0.004	0.057	0.25	3	-0.32	5	8
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.021	0.049	0.2	1	-0.3	4	5
eIF4E/eIF4G1/eIF4A1	0.004	0.05	-10000	0	-0.26	16	16
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.025	0.03	-10000	0	-0.2	7	7
mTOR/RHEB/GTP/Raptor/GBL	-0.005	0.033	0.14	11	-0.15	3	14
FKBP1A	0.02	0.005	-10000	0	-10000	0	0
RHEB/GTP	-0.017	0.037	-10000	0	-0.19	2	2
mol:Amino Acids	0	0	-10000	0	-0.001	2	2
FKBP12/Rapamycin	0.015	0.004	-10000	0	-10000	0	0
PDPK1	-0.018	0.021	-10000	0	-0.2	4	4
EIF4E	0.021	0.003	-10000	0	-10000	0	0
ASK1/PP5C	-0.031	0.18	-10000	0	-0.52	56	56
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.005	0.039	0.17	1	-0.23	12	13
TSC1/TSC2	-0.012	0.047	0.27	1	-0.23	2	3
tumor necrosis factor receptor activity	0	0	0.001	2	-10000	0	2
RPS6	0.019	0.006	-10000	0	-10000	0	0
PPP5C	0.02	0.005	-10000	0	-10000	0	0
EIF4G1	0.02	0.004	-10000	0	-10000	0	0
IRS1	0.002	0.027	-10000	0	-0.24	6	6
INS	0.017	0.003	-10000	0	-10000	0	0
PTEN	0.021	0.004	-10000	0	-10000	0	0
PDK2	-0.017	0.024	0.17	1	-0.2	5	6
EIF4EBP1	-0.058	0.29	-10000	0	-1	41	41
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
PPP2R5D	-0.003	0.079	0.21	3	-0.39	15	18
peptide biosynthetic process	-0.016	0.013	0.17	2	-10000	0	2
RHEB	0.02	0.005	-10000	0	-10000	0	0
EIF4A1	0.02	0.006	-10000	0	-10000	0	0
mol:Rapamycin	0	0.001	0.003	17	-0.002	1	18
EEF2	-0.016	0.013	0.17	2	-10000	0	2
eIF4E/4E-BP1	-0.046	0.27	-10000	0	-0.96	41	41

IFN-gamma 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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.043	0.058	0.21	29	-0.16	9	38
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	0.02	0.005	-10000	0	-10000	0	0
STAT1 (dimer)/Cbp/p300	-0.009	0.056	0.27	3	-10000	0	3
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.036	0.027	-10000	0	-0.18	2	2
antigen processing and presentation of peptide antigen via MHC class I	-0.019	0.038	-10000	0	-0.28	1	1
CaM/Ca2+	0.041	0.053	-10000	0	-0.16	8	8
RAP1A	0.02	0.004	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	-0.011	0.047	0.16	1	-10000	0	1
AKT1	-0.011	0.06	0.27	9	-10000	0	9
MAP2K1	-0.013	0.05	0.21	7	-10000	0	7
MAP3K11	-0.011	0.051	0.23	6	-0.16	1	7
IFNGR1	0.019	0.012	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	0.001	0.12	0.23	4	-0.32	46	50
Rap1/GTP	-0.029	0.025	-10000	0	-10000	0	0
CRKL/C3G	0.029	0.009	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.054	0.059	-10000	0	-0.17	7	7
CEBPB	-0.008	0.11	0.32	2	-0.42	17	19
STAT3	0.021	0.003	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.051	0.08	-10000	0	-0.67	3	3
STAT1	-0.01	0.051	0.23	6	-10000	0	6
CALM1	0.02	0.005	-10000	0	-10000	0	0
IFN-gamma (dimer)	0.03	0.087	0.32	31	-0.33	8	39
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
STAT1 (dimer)/PIAS1	-0.01	0.057	0.27	5	-10000	0	5
CEBPB/PTGES2/Cbp/p300	0.004	0.069	-10000	0	-0.31	11	11
mol:Ca2+	0.041	0.055	0.2	29	-0.16	9	38
MAPK3	0.001	0.068	-10000	0	-0.47	3	3
STAT1 (dimer)	-0.021	0.053	-10000	0	-0.39	1	1
MAPK1	-0.022	0.14	-10000	0	-0.68	20	20
JAK2	0.018	0.024	-10000	0	-0.32	2	2
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
JAK1	0.02	0.011	-10000	0	-10000	0	0
CAMK2D	0.021	0.003	-10000	0	-10000	0	0
DAPK1	-0.009	0.1	0.28	2	-0.53	12	14
SMAD7	-0.003	0.037	0.19	6	-0.16	2	8
CBL/CRKL/C3G	-0.011	0.056	0.27	4	-10000	0	4
PI3K	0.038	0.051	-10000	0	-0.16	7	7
IFNG	0.031	0.087	0.32	31	-0.33	8	39
apoptosis	-0.007	0.098	0.3	1	-0.42	20	21
CAMK2G	0.021	0.003	-10000	0	-10000	0	0
STAT3 (dimer)	0.021	0.003	-10000	0	-10000	0	0
CAMK2A	-0.012	0.1	0.32	1	-0.33	48	49
CAMK2B	0.064	0.11	0.32	75	-10000	0	75
FRAP1	-0.012	0.056	0.26	9	-10000	0	9
PRKCD	-0.012	0.061	0.28	9	-10000	0	9
RAP1B	0.02	0.005	-10000	0	-10000	0	0
negative regulation of cell growth	-0.019	0.038	-10000	0	-0.28	1	1
PTPN2	0.02	0.005	-10000	0	-10000	0	0
EP300	0.02	0.005	-10000	0	-10000	0	0
IRF1	-0.01	0.05	0.24	6	-10000	0	6
STAT1 (dimer)/PIASy	-0.01	0.056	0.27	5	-10000	0	5
SOCS1	0.014	0.081	-10000	0	-1	3	3
mol:GDP	-0.012	0.051	0.25	3	-10000	0	3
CASP1	-0.005	0.042	0.18	7	-0.19	6	13
PTGES2	0.021	0.004	-10000	0	-10000	0	0
IRF9	-0.003	0.035	-10000	0	-0.16	1	1
mol:PI-3-4-5-P3	0.026	0.042	-10000	0	-0.16	8	8
RAP1/GDP	-0.026	0.034	-10000	0	-10000	0	0
CBL	-0.009	0.05	0.23	6	-10000	0	6
MAP3K1	-0.01	0.05	0.23	6	-10000	0	6
PIAS1	0.021	0.004	-10000	0	-10000	0	0
PIAS4	0.02	0.006	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.019	0.038	-10000	0	-0.28	1	1
PTPN11	-0.006	0.051	0.15	32	-0.16	7	39
CREBBP	0.021	0.004	-10000	0	-10000	0	0
RAPGEF1	0.021	0.004	-10000	0	-10000	0	0

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	-0.003	0.07	0.24	3	-0.32	12	15
BAG4	0.019	0.007	-10000	0	-10000	0	0
BAD	-0.001	0.036	0.23	4	-0.13	5	9
NFKBIA	0.018	0.008	-10000	0	-10000	0	0
BIRC3	0.022	0.037	0.32	5	-0.32	2	7
BAX	-0.001	0.03	0.16	2	-0.13	5	7
EnzymeConsortium:3.1.4.12	0.001	0.02	0.074	2	-0.083	8	10
IKBKB	0.008	0.083	0.28	9	-0.36	8	17
MAP2K2	-0.005	0.036	0.16	11	-10000	0	11
MAP2K1	-0.005	0.039	0.16	14	-0.15	1	15
SMPD1	0	0.025	0.13	1	-0.12	8	9
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.005	0.075	0.25	5	-0.37	8	13
MAP2K4	-0.002	0.037	0.19	9	-0.15	1	10
protein ubiquitination	0.003	0.079	0.28	6	-0.36	8	14
EnzymeConsortium:2.7.1.37	-0.007	0.042	0.15	12	-0.17	1	13
response to UV	0	0	0.002	14	-0.002	1	15
RAF1	-0.002	0.038	0.17	11	-0.15	1	12
CRADD	0.021	0.021	0.32	1	-0.33	1	2
mol:ceramide	0.002	0.032	0.1	4	-0.12	9	13
I-kappa-B-alpha/RELA/p50/ubiquitin	0.024	0.011	-10000	0	-10000	0	0
MADD	0.021	0.003	-10000	0	-10000	0	0
MAP3K1	0.001	0.039	0.19	10	-0.13	5	15
TRADD	0.02	0.004	-10000	0	-10000	0	0
RELA/p50	0.021	0.004	-10000	0	-10000	0	0
MAPK3	-0.003	0.039	0.16	11	-10000	0	11
MAPK1	-0.006	0.043	0.16	10	-0.19	4	14
p50/RELA/I-kappa-B-alpha	0.026	0.012	-10000	0	-10000	0	0
FADD	0.001	0.071	0.21	5	-0.34	10	15
KSR1	0	0.039	0.17	11	-0.13	5	16
MAPK8	-0.005	0.042	0.19	14	-0.15	1	15
TRAF2	0.021	0.004	-10000	0	-10000	0	0
response to radiation	0	0	0.002	2	-10000	0	2
CHUK	-0.004	0.072	0.33	3	-0.36	8	11
TNF R/SODD	0.026	0.012	-10000	0	-10000	0	0
TNF	0.011	0.06	0.32	1	-0.33	15	16
CYCS	0.008	0.042	0.15	11	-0.13	4	15
IKBKG	0.001	0.076	0.28	5	-0.34	8	13
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.002	0.069	-10000	0	-0.34	11	11
RELA	0.021	0.004	-10000	0	-10000	0	0
RIPK1	0.021	0.004	-10000	0	-10000	0	0
AIFM1	0.003	0.038	0.16	5	-0.13	4	9
TNF/TNF R/SODD	0.029	0.042	0.22	1	-0.19	14	15
TNFRSF1A	0.02	0.005	-10000	0	-10000	0	0
response to heat	0	0	0.002	2	-10000	0	2
CASP8	0.01	0.085	-10000	0	-0.57	10	10
NSMAF	0.008	0.081	0.23	9	-0.33	11	20
response to hydrogen peroxide	0	0	0.002	14	-0.002	1	15
BCL2	0.019	0.021	0.32	1	-0.33	1	2

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	0.098	0.16	0.38	48	-0.42	2	50
RAD9A	0.021	0.004	-10000	0	-10000	0	0
AP1	0.023	0.062	-10000	0	-0.22	29	29
IFNAR2	0.028	0.014	-10000	0	-10000	0	0
AKT1	0.022	0.034	0.17	2	-0.21	3	5
ER alpha/Oestrogen	0.018	0.041	0.22	9	-0.21	8	17
NFX1/SIN3/HDAC complex	0.012	0.05	-10000	0	-0.29	5	5
EGF	0.074	0.12	0.33	91	-0.32	5	96
SMG5	0.018	0.008	-10000	0	-10000	0	0
SMG6	0.019	0.006	-10000	0	-10000	0	0
SP3/HDAC2	0.04	0.025	-10000	0	-10000	0	0
TERT/c-Abl	0.09	0.14	0.37	23	-0.39	2	25
SAP18	0.021	0.006	-10000	0	-10000	0	0
MRN complex	0.035	0.017	-10000	0	-10000	0	0
WT1	0.012	0.096	0.34	10	-0.32	31	41
WRN	0.018	0.008	-10000	0	-10000	0	0
SP1	0.031	0.019	-10000	0	-10000	0	0
SP3	0.024	0.008	-10000	0	-10000	0	0
TERF2IP	0.02	0.005	-10000	0	-10000	0	0
Telomerase/Nucleolin	0.051	0.1	-10000	0	-0.39	2	2
Mad/Max	0.039	0.017	-10000	0	-10000	0	0
TERT	0.099	0.16	0.4	34	-0.42	2	36
CCND1	0.087	0.18	0.46	11	-0.84	7	18
MAX	0.024	0.008	-10000	0	-10000	0	0
RBBP7	0.022	0.005	-10000	0	-10000	0	0
RBBP4	0.022	0.004	-10000	0	-10000	0	0
TERF2	-0.017	0.015	-10000	0	-10000	0	0
PTGES3	0.021	0.004	-10000	0	-10000	0	0
SIN3A	0.022	0.005	-10000	0	-10000	0	0
Telomerase/911	0.054	0.062	0.22	7	-0.26	2	9
CDKN1B	0.001	0.04	0.22	2	-10000	0	2
RAD1	0.018	0.008	-10000	0	-10000	0	0
XRCC5	0.021	0.003	-10000	0	-10000	0	0
XRCC6	0.02	0.004	-10000	0	-10000	0	0
SAP30	0.022	0.005	-10000	0	-10000	0	0
TRF2/PARP2	0.028	0.011	-10000	0	-10000	0	0
UBE3A	0.023	0.008	-10000	0	-10000	0	0
JUN	0.022	0.027	-10000	0	-0.32	3	3
E6	0.003	0.005	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.022	0.014	-10000	0	-10000	0	0
FOS	0.006	0.077	-10000	0	-0.32	27	27
IFN-gamma/IRF1	0.046	0.063	0.25	31	-0.22	8	39
PARP2	0.02	0.005	-10000	0	-10000	0	0
BLM	0.049	0.088	0.32	48	-10000	0	48
Telomerase	0.037	0.087	0.24	8	-0.42	6	14
IRF1	0.025	0.009	-10000	0	-10000	0	0
ESR1	0.021	0.059	0.33	9	-0.32	8	17
KU/TER	0.03	0.007	-10000	0	-10000	0	0
ATM/TRF2	0.029	0.008	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.011	0.057	-10000	0	-0.28	8	8
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.012	0.056	-10000	0	-0.29	7	7
HDAC1	0.022	0.003	-10000	0	-10000	0	0
HDAC2	0.028	0.018	-10000	0	-10000	0	0
ATM	0.009	0.008	-10000	0	-10000	0	0
SMAD3	-0.02	0.009	-10000	0	-10000	0	0
ABL1	0.021	0.004	-10000	0	-10000	0	0
MXD1	0.024	0.008	-10000	0	-10000	0	0
MRE11A	0.02	0.004	-10000	0	-10000	0	0
HUS1	0.019	0.006	-10000	0	-10000	0	0
RPS6KB1	0.02	0.004	-10000	0	-10000	0	0
TERT/NF kappa B1/14-3-3	0.094	0.14	0.39	13	-0.44	1	14
NR2F2	0.004	0.026	-10000	0	-10000	0	0
MAPK3	-0.004	0.02	-10000	0	-10000	0	0
MAPK1	-0.005	0.019	-10000	0	-10000	0	0
TGFB1/TGF beta receptor Type II	0.008	0.02	-10000	0	-10000	0	0
NFKB1	0.021	0.003	-10000	0	-10000	0	0
HNRNPC	0.02	0.004	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.009	0.008	-10000	0	-10000	0	0
NBN	0.019	0.007	-10000	0	-10000	0	0
EGFR	0.016	0.045	0.33	1	-0.32	8	9
mol:Oestrogen	0.002	0.003	-10000	0	-10000	0	0
EGF/EGFR	0.057	0.088	0.24	75	-0.22	12	87
MYC	0.02	0.025	-10000	0	-0.32	2	2
IL2	0.03	0.019	-10000	0	-10000	0	0
KU	0.03	0.007	-10000	0	-10000	0	0
RAD50	0.02	0.005	-10000	0	-10000	0	0
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
TGFB1	0.008	0.02	-10000	0	-10000	0	0
TRF2/BLM	0.046	0.056	0.22	45	-10000	0	45
FRAP1	0	0	-10000	0	-10000	0	0
KU/TERT	0.1	0.14	0.38	21	-0.4	2	23
SP1/HDAC2	0.047	0.036	-10000	0	-10000	0	0
PINX1	0.018	0.008	-10000	0	-10000	0	0
Telomerase/EST1A	0.047	0.1	-10000	0	-0.38	2	2
Smad3/Myc	-0.019	0.015	-10000	0	-0.19	2	2
911 complex	0.032	0.019	-10000	0	-10000	0	0
IFNG	0.037	0.086	0.33	31	-0.32	8	39
Telomerase/PinX1	0.042	0.1	-10000	0	-0.38	2	2
Telomerase/AKT1/mTOR/p70S6K	0.05	0.089	0.26	11	-0.4	6	17
SIN3B	0.022	0.006	-10000	0	-10000	0	0
YWHAE	0.019	0.006	-10000	0	-10000	0	0
Telomerase/EST1B	0.044	0.099	-10000	0	-0.39	2	2
response to DNA damage stimulus	0.002	0.019	-10000	0	-10000	0	0
MRN complex/TRF2/Rap1	0.047	0.026	-10000	0	-10000	0	0
TRF2/WRN	0.025	0.012	-10000	0	-10000	0	0
Telomerase/hnRNP C1/C2	0.05	0.1	-10000	0	-0.39	2	2
E2F1	0.031	0.032	0.32	5	-10000	0	5
ZNFX1	0.021	0.006	-10000	0	-10000	0	0
PIF1	0.064	0.11	0.32	73	-10000	0	73
NCL	0.021	0.003	-10000	0	-10000	0	0
DKC1	0.02	0.004	-10000	0	-10000	0	0
telomeric DNA binding	0	0	-10000	0	-10000	0	0

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.041	0.048	0.23	1	-0.21	14	15
MAP4K1	0.017	0.031	-10000	0	-0.33	4	4
MAP3K8	0.02	0.016	-10000	0	-0.33	1	1
PRKCB	0.011	0.057	-10000	0	-0.33	14	14
DBNL	0.019	0.006	-10000	0	-10000	0	0
CRKL	0.02	0.005	-10000	0	-10000	0	0
MAP3K1	0	0.051	-10000	0	-0.38	4	4
JUN	-0.012	0.13	-10000	0	-0.56	24	24
MAP3K7	0.002	0.044	-10000	0	-0.31	4	4
GRAP2	0.011	0.057	-10000	0	-0.33	14	14
CRK	0.019	0.006	-10000	0	-10000	0	0
MAP2K4	-0.002	0.069	0.2	2	-0.39	8	10
LAT	0.021	0.014	0.32	1	-10000	0	1
LCP2	0.018	0.027	-10000	0	-0.33	3	3
MAPK8	-0.007	0.13	-10000	0	-0.58	24	24
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.007	0.059	-10000	0	-0.36	7	7
LAT/GRAP2/SLP76/HPK1/HIP-55	0.047	0.043	-10000	0	-0.22	7	7

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.018	0.057	0.34	2	-10000	0	2
CRKL	-0.01	0.045	0.2	10	-10000	0	10
mol:DAG	0.01	0.033	0.24	1	-0.22	1	2
HRAS	0	0.074	0.25	14	-10000	0	14
MAPK8	-0.001	0.058	0.17	50	-10000	0	50
RAP1A	-0.01	0.047	0.2	10	-10000	0	10
GAB1	-0.011	0.047	0.21	8	-0.25	1	9
MAPK14	-0.002	0.057	0.17	48	-10000	0	48
EPO	0.011	0.034	0.32	4	-10000	0	4
PLCG1	0.01	0.033	0.24	1	-0.23	1	2
EPOR/TRPC2/IP3 Receptors	0.022	0.009	-10000	0	-10000	0	0
RAPGEF1	0.021	0.004	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.038	0.03	0.21	3	-0.2	4	7
GAB1/SHC/GRB2/SOS1	-0.016	0.046	0.24	4	-10000	0	4
EPO/EPOR (dimer)	0.031	0.022	0.22	4	-10000	0	4
IRS2	-0.01	0.046	0.2	10	-10000	0	10
STAT1	0.011	0.036	0.32	1	-0.23	1	2
STAT5B	0.011	0.034	0.28	1	-0.23	1	2
cell proliferation	-0.004	0.06	0.17	49	-10000	0	49
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.025	0.034	-10000	0	-0.28	1	1
TEC	-0.01	0.047	0.2	10	-10000	0	10
SOCS3	0.018	0.031	-10000	0	-0.33	4	4
STAT1 (dimer)	0.011	0.036	0.32	1	-0.22	1	2
JAK2	0.019	0.023	-10000	0	-0.33	2	2
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
EPO/EPOR (dimer)/JAK2	0.045	0.038	0.36	1	-0.16	2	3
EPO/EPOR	0.031	0.022	0.22	4	-10000	0	4
LYN	0.02	0.006	-10000	0	-10000	0	0
TEC/VAV2	-0.013	0.046	0.26	4	-10000	0	4
elevation of cytosolic calcium ion concentration	0.022	0.009	-10000	0	-10000	0	0
SHC1	0.018	0.016	0.32	1	-10000	0	1
EPO/EPOR (dimer)/LYN	0.038	0.024	0.22	3	-10000	0	3
mol:IP3	0.01	0.033	0.24	1	-0.22	1	2
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.015	0.052	0.26	3	-0.29	1	4
SH2B3	0.021	0.023	-10000	0	-0.33	2	2
NFKB1	-0.001	0.059	0.17	51	-10000	0	51
EPO/EPOR (dimer)/JAK2/SOCS3	0.003	0.044	0.19	2	-0.23	13	15
PTPN6	-0.008	0.042	0.14	31	-0.16	2	33
TEC/VAV2/GRB2	-0.016	0.047	0.26	4	-10000	0	4
EPOR	0.022	0.009	-10000	0	-10000	0	0
INPP5D	0.019	0.027	-10000	0	-0.33	3	3
mol:GDP	-0.017	0.046	0.24	4	-10000	0	4
SOS1	0.021	0.003	-10000	0	-10000	0	0
PLCG2	0.018	0.027	-10000	0	-0.33	3	3
CRKL/CBL/C3G	-0.016	0.046	0.26	4	-10000	0	4
VAV2	-0.01	0.047	0.2	9	-10000	0	9
CBL	-0.009	0.047	0.2	10	-10000	0	10
SHC/Grb2/SOS1	0.024	0.023	-10000	0	-10000	0	0
STAT5A	0.01	0.038	0.28	1	-0.3	2	3
GRB2	0.02	0.004	-10000	0	-10000	0	0
STAT5 (dimer)	0.022	0.039	0.37	1	-0.34	1	2
LYN/PLCgamma2	0.026	0.022	-10000	0	-0.23	3	3
PTPN11	0.021	0.004	-10000	0	-10000	0	0
BTK	-0.017	0.057	0.22	7	-0.28	3	10
BCL2	0.009	0.075	0.39	2	-0.46	1	3

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.02	0.005	-10000	0	-10000	0	0
NFATC1	-0.014	0.097	0.27	1	-0.4	15	16
NFATC2	-0.012	0.06	0.18	6	-0.25	13	19
NFATC3	0.006	0.021	-10000	0	-0.3	2	2
YWHAE	0.019	0.006	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.019	0.094	0.26	1	-0.34	22	23
Exportin 1/Ran/NUP214	0.04	0.013	0.22	1	-10000	0	1
mol:DAG	-0.001	0.002	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.002	0.086	-10000	0	-0.32	19	19
BCL2/BAX	0.027	0.018	0.23	1	-0.23	1	2
CaM/Ca2+/Calcineurin A alpha-beta B1	0.008	0.015	-10000	0	-10000	0	0
CaM/Ca2+	0.008	0.015	-10000	0	-10000	0	0
BAX	0.02	0.004	-10000	0	-10000	0	0
MAPK14	0.013	0.016	-10000	0	-10000	0	0
BAD	0.021	0.003	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.005	0.085	0.24	1	-0.34	18	19
Calcineurin A alpha-beta B1/BCL2	0.019	0.021	0.32	1	-0.32	1	2
FKBP8	0.019	0.016	-10000	0	-0.33	1	1
activation-induced cell death of T cells	0.005	0.084	0.34	18	-0.24	1	19
KPNB1	0.021	0.004	-10000	0	-10000	0	0
KPNA2	0.023	0.03	0.32	5	-10000	0	5
XPO1	0.021	0.002	-10000	0	-10000	0	0
SFN	0.025	0.043	0.32	9	-0.33	1	10
MAP3K8	0.012	0.022	-10000	0	-0.33	1	1
NFAT4/CK1 alpha	0.007	0.026	-10000	0	-0.16	2	2
MEF2D/NFAT1/Cbp/p300	-0.019	0.11	-10000	0	-0.23	83	83
CABIN1	-0.019	0.095	0.26	1	-0.35	22	23
CALM1	0.012	0.017	-10000	0	-10000	0	0
RAN	0.021	0.014	0.32	1	-10000	0	1
MAP3K1	0.02	0.005	-10000	0	-10000	0	0
CAMK4	0.016	0.043	0.32	1	-0.33	7	8
mol:Ca2+	-0.002	0.005	-10000	0	-10000	0	0
MAPK3	0.021	0.003	-10000	0	-10000	0	0
YWHAH	0.02	0.004	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.027	0.022	-10000	0	-0.23	3	3
YWHAB	0.02	0.005	-10000	0	-10000	0	0
MAPK8	0.013	0.017	-10000	0	-10000	0	0
MAPK9	0.02	0.004	-10000	0	-10000	0	0
YWHAG	0.02	0.004	-10000	0	-10000	0	0
FKBP1A	0.02	0.005	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	-0.015	0.1	0.26	2	-0.4	18	20
PRKCH	0.021	0.004	-10000	0	-10000	0	0
CABIN1/Cbp/p300	0.017	0.028	-10000	0	-10000	0	0
CASP3	0.013	0.016	-10000	0	-10000	0	0
PIM1	0.021	0.004	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.009	0.011	-10000	0	-10000	0	0
apoptosis	0.012	0.016	0.15	1	-10000	0	1
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.001	0.039	-10000	0	-0.3	3	3
PRKCB	0.011	0.057	-10000	0	-0.33	14	14
PRKCE	0.018	0.034	-10000	0	-0.33	5	5
JNK2/NFAT4	0.016	0.036	-10000	0	-0.27	2	2
BAD/BCL-XL	0.029	0.008	-10000	0	-10000	0	0
PRKCD	0.02	0.004	-10000	0	-10000	0	0
NUP214	0.02	0.004	-10000	0	-10000	0	0
PRKCZ	0.011	0.031	-10000	0	-0.33	3	3
PRKCA	0.019	0.022	-10000	0	-0.33	2	2
PRKCG	0.049	0.09	0.32	49	-10000	0	49
PRKCQ	-0.022	0.11	-10000	0	-0.33	63	63
FKBP38/BCL2	0.027	0.021	0.23	1	-0.23	2	3
EP300	0.011	0.02	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.02	0.005	-10000	0	-10000	0	0
NFATc/JNK1	-0.006	0.097	0.26	1	-0.38	15	16
CaM/Ca2+/FKBP38	0.017	0.023	-10000	0	-0.2	1	1
FKBP12/FK506	0.015	0.003	-10000	0	-10000	0	0
CSNK1A1	-0.015	0.008	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0.015	0.033	0.21	1	-0.19	7	8
NFATc/ERK1	-0.003	0.097	0.26	1	-0.38	14	15
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	0.001	0.095	-10000	0	-0.32	22	22
NR4A1	-0.058	0.16	0.23	8	-0.36	92	100
GSK3B	0.013	0.016	-10000	0	-10000	0	0
positive T cell selection	0.006	0.021	-10000	0	-0.3	2	2
NFAT1/CK1 alpha	-0.01	0.042	0.13	1	-0.2	8	9
RCH1/ KPNB1	0.032	0.021	0.23	5	-10000	0	5
YWHAQ	0.021	0.003	-10000	0	-10000	0	0
PRKACA	0.013	0.016	-10000	0	-10000	0	0
AKAP5	0.019	0.027	-10000	0	-0.33	3	3
MEF2D	0.009	0.019	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.019	0.007	-10000	0	-10000	0	0
NFATc/p38 alpha	-0.009	0.094	-10000	0	-0.38	15	15
CREBBP	0.011	0.02	-10000	0	-10000	0	0
BCL2	0.019	0.021	0.32	1	-0.33	1	2

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.021	0.002	-10000	0	-10000	0	0
HDAC3	0.02	0.004	-10000	0	-10000	0	0
VDR	0.021	0.021	0.32	1	-0.33	1	2
Cbp/p300/PCAF	0.039	0.013	-10000	0	-10000	0	0
EP300	0.02	0.005	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.013	0.04	-10000	0	-0.34	2	2
KAT2B	0.02	0.004	-10000	0	-10000	0	0
MAPK14	0.021	0.004	-10000	0	-10000	0	0
AKT1	0.007	0.042	0.23	2	-0.2	4	6
RAR alpha/9cRA/Cyclin H	0.035	0.047	-10000	0	-0.23	2	2
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.008	0.053	-10000	0	-0.34	5	5
CDC2	0	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.021	0.034	-10000	0	-0.19	6	6
NCOR2	0.021	0.003	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.015	0.014	0.22	1	-0.22	1	2
RXRs/RARs/NRIP1/9cRA	-0.01	0.098	0.34	3	-0.42	13	16
NCOA2	0.016	0.035	-10000	0	-0.33	5	5
NCOA3	0.02	0.005	-10000	0	-10000	0	0
NCOA1	0.021	0.002	-10000	0	-10000	0	0
VDR/VDR/DNA	0.021	0.021	0.32	1	-0.32	1	2
RARG	0.021	0.003	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.027	0.008	-10000	0	-10000	0	0
MAPK3	0.021	0.003	-10000	0	-10000	0	0
MAPK1	0.02	0.005	-10000	0	-10000	0	0
MAPK8	0.021	0.003	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.006	0.086	0.28	1	-0.36	13	14
RARA	0.017	0.034	0.19	3	-0.2	2	5
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.006	0.053	-10000	0	-0.3	7	7
PRKCA	0.02	0.022	-10000	0	-0.33	2	2
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.016	0.11	0.33	2	-0.46	13	15
RXRG	-0.092	0.13	0.25	2	-0.25	194	196
RXRA	0.01	0.029	0.18	4	-0.19	2	6
RXRB	0.023	0.045	0.24	3	-0.25	2	5
VDR/Vit D3/DNA	0.015	0.014	0.22	1	-0.22	1	2
RBP1	0.023	0.031	0.32	4	-0.33	1	5
CRBP1/9-cic-RA	0.017	0.021	0.22	4	-0.22	1	5
RARB	0.02	0.022	-10000	0	-0.33	2	2
PRKCG	0.049	0.09	0.32	49	-10000	0	49
MNAT1	0.021	0.004	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.012	0.086	0.27	1	-0.39	13	14
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.005	0.083	0.27	3	-0.37	11	14
proteasomal ubiquitin-dependent protein catabolic process	0.01	0.077	0.23	4	-0.34	11	15
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.017	0.11	0.33	2	-0.46	13	15
positive regulation of DNA binding	0.025	0.039	-10000	0	-0.22	2	2
NRIP1	-0.015	0.11	0.46	1	-0.5	8	9
RXRs/RARs	-0.019	0.11	0.28	1	-0.46	14	15
RXRs/RXRs/DNA/9cRA	-0.017	0.08	0.28	1	-0.37	13	14
PRKACA	0.02	0.005	-10000	0	-10000	0	0
CDK7	0.02	0.005	-10000	0	-10000	0	0
TFIIH	0.04	0.012	-10000	0	-10000	0	0
RAR alpha/9cRA	0.043	0.039	-10000	0	-0.22	1	1
CCNH	0.02	0.005	-10000	0	-10000	0	0
CREBBP	0.021	0.004	-10000	0	-10000	0	0
RAR gamma2/9cRA	0.035	0.017	-10000	0	-10000	0	0

Arf6 trafficking events

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
SLC2A4	0.017	0.031	-10000	0	-0.33	4	4
CLTC	0.015	0.057	0.23	1	-0.44	5	6
calcium ion-dependent exocytosis	0.01	0.031	0.19	3	-0.16	4	7
Dynamin 2/GTP	-0.004	0.04	0.12	41	-10000	0	41
EXOC4	0.02	0.005	-10000	0	-10000	0	0
CD59	0.011	0.036	-10000	0	-0.31	4	4
CPE	-0.005	0.041	0.19	19	-10000	0	19
CTNNB1	0.021	0.004	-10000	0	-10000	0	0
membrane fusion	0.01	0.025	-10000	0	-10000	0	0
CTNND1	-0.004	0.049	0.19	25	-10000	0	25
DNM2	0.02	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.007	0.044	0.18	6	-0.26	4	10
TSHR	0.007	0.056	0.17	54	-10000	0	54
INS	0.001	0.074	-10000	0	-0.51	10	10
BIN1	0.021	0.001	-10000	0	-10000	0	0
mol:Choline	0.01	0.025	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.006	0.059	0.18	47	-10000	0	47
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.02	0.004	-10000	0	-10000	0	0
mol:Ca2+	-0.004	0.039	0.12	41	-10000	0	41
JUP	0.01	0.031	-10000	0	-0.3	3	3
ASAP2/amphiphysin II	0.038	0.014	-10000	0	-0.18	1	1
ARF6/GTP	0.015	0.003	-10000	0	-10000	0	0
CDH1	0.01	0.037	-10000	0	-0.31	4	4
clathrin-independent pinocytosis	0.015	0.003	-10000	0	-10000	0	0
MAPK8IP3	0.021	0.014	0.32	1	-10000	0	1
positive regulation of endocytosis	0.015	0.003	-10000	0	-10000	0	0
EXOC2	0.021	0.004	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.007	0.019	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.021	0.004	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.032	0.045	0.29	4	-10000	0	4
positive regulation of phagocytosis	-0.012	0.003	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.027	0.011	0.21	1	-10000	0	1
ACAP1	0.013	0.029	-10000	0	-0.15	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	-0.01	0.061	-10000	0	-0.31	4	4
clathrin heavy chain/ACAP1	0.014	0.048	0.21	5	-0.32	4	9
JIP4/KLC1	0.037	0.012	-10000	0	-10000	0	0
EXOC1	0.021	0.003	-10000	0	-10000	0	0
exocyst	0.007	0.02	-10000	0	-10000	0	0
RALA/GTP	0.014	0.005	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.027	0.007	-10000	0	-10000	0	0
receptor recycling	0.015	0.003	-10000	0	-10000	0	0
CTNNA1	-0.004	0.049	0.19	24	-10000	0	24
NME1	0.006	0.059	0.18	47	-10000	0	47
clathrin coat assembly	0.015	0.059	0.23	1	-0.4	6	7
IL2RA	0.014	0.04	-10000	0	-0.33	4	4
VAMP3	-0.013	0.003	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	0.016	0.048	-10000	0	-0.31	5	5
EXOC6	0.021	0.003	-10000	0	-10000	0	0
PLD1	0.005	0.006	-10000	0	-10000	0	0
PLD2	0.005	0.005	-10000	0	-10000	0	0
EXOC5	0.021	0.004	-10000	0	-10000	0	0
PIP5K1C	0.007	0.042	0.18	4	-0.26	4	8
SDC1	0.011	0.037	-10000	0	-0.31	4	4
ARF6/GDP	0.026	0.033	0.13	44	-10000	0	44
EXOC7	0.02	0.004	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.034	0.047	-10000	0	-0.3	4	4
mol:Phosphatidic acid	0.01	0.025	-10000	0	-10000	0	0
endocytosis	-0.037	0.014	0.18	1	-10000	0	1
SCAMP2	0.021	0.004	-10000	0	-10000	0	0
ADRB2	-0.038	0.089	0.21	1	-0.45	6	7
EXOC3	0.016	0.009	-10000	0	-10000	0	0
ASAP2	0.02	0.016	-10000	0	-0.33	1	1
Dynamin 2/GDP	0.031	0.044	0.17	43	-10000	0	43
KLC1	0.02	0.005	-10000	0	-10000	0	0
AVPR2	-0.014	0.087	0.27	8	-0.41	6	14
RALA	0.019	0.006	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.024	0.049	0.33	2	-0.29	4	6

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.013	0.012	-10000	0	-10000	0	0
TRAF2/ASK1	0.025	0.01	-10000	0	-10000	0	0
ATM	0.02	0.005	-10000	0	-10000	0	0
MAP2K3	-0.006	0.091	0.29	2	-0.31	25	27
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	-0.003	0.083	0.25	3	-0.36	13	16
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.019	0.036	0.32	2	-0.33	4	6
TXN	0.005	0.012	0.16	3	-10000	0	3
CALM1	0.02	0.005	-10000	0	-10000	0	0
GADD45A	0.021	0.003	-10000	0	-10000	0	0
GADD45B	0.018	0.022	-10000	0	-0.33	2	2
MAP3K1	0.02	0.005	-10000	0	-10000	0	0
MAP3K6	0.021	0.003	-10000	0	-10000	0	0
MAP3K7	0.019	0.006	-10000	0	-10000	0	0
MAP3K4	0.019	0.006	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.028	0.01	-10000	0	-10000	0	0
TAK1/TAB family	0	0.018	0.13	2	-0.13	1	3
RAC1/OSM/MEKK3	0.034	0.017	-10000	0	-0.16	1	1
TRAF2	0.021	0.004	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.004	0.073	-10000	0	-0.27	19	19
TRAF6	0.004	0.001	-10000	0	-10000	0	0
RAC1	0.019	0.007	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	0.064	0.11	0.32	75	-10000	0	75
CCM2	0.019	0.006	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	0.05	0.065	0.21	72	-10000	0	72
MAPK11	0.018	0.022	-10000	0	-0.33	2	2
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.055	0.062	0.21	65	-10000	0	65
OSM/MEKK3	0.027	0.016	-10000	0	-0.23	1	1
TAOK1	0.007	0.011	-10000	0	-0.25	1	1
TAOK2	0.007	0.002	-10000	0	-10000	0	0
TAOK3	0.007	0.002	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.021	0.004	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.019	0.006	-10000	0	-10000	0	0
MAP3K10	0.018	0.027	-10000	0	-0.33	3	3
MAP3K3	0.02	0.016	-10000	0	-0.33	1	1
TRX/ASK1	0.015	0.019	0.15	1	-0.099	10	11
GADD45/MTK1/MTK1	0.041	0.032	0.21	2	-0.2	4	6

Ras signaling in the CD4+ TCR 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	0.011	0.1	-9999	-0.41	15	15
MAP3K8	0.018	0.018	-9999	-0.33	1	1
FOS	0.007	0.084	-9999	-0.37	12	12
PRKCA	0.017	0.025	-9999	-0.33	2	2
PTPN7	0.017	0.014	-9999	-10000	0	0
HRAS	0.02	0.006	-9999	-10000	0	0
PRKCB	0.009	0.057	-9999	-0.33	14	14
NRAS	0.02	0.007	-9999	-10000	0	0
RAS family/GTP	0.032	0.02	-9999	-10000	0	0
MAPK3	0.014	0.041	-9999	-0.34	1	1
MAP2K1	-0.002	0.079	-9999	-0.4	13	13
ELK1	0.018	0.014	-9999	-10000	0	0
BRAF	-0.001	0.057	-9999	-0.34	12	12
mol:GTP	0	0.001	-9999	-0.004	27	27
MAPK1	0	0.093	-9999	-0.43	18	18
RAF1	-0.003	0.065	-9999	-0.35	15	15
KRAS	0.019	0.007	-9999	-10000	0	0

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.02	0.016	-10000	0	-0.33	1	1
SPHK1	0.023	0.03	0.32	5	-10000	0	5
GNAI2	0.02	0.004	-10000	0	-10000	0	0
mol:S1P	0.007	0.015	-10000	0	-0.22	1	1
GNAO1	0.021	0.035	0.32	4	-0.33	2	6
mol:Sphinganine-1-P	-0.014	0.02	0.15	5	-0.23	1	6
growth factor activity	0	0	-10000	0	-10000	0	0
S1P/S1P2/G12/G13	0.034	0.033	-10000	0	-0.2	2	2
GNAI3	0.02	0.004	-10000	0	-10000	0	0
G12/G13	0.027	0.011	-10000	0	-10000	0	0
S1PR3	0.021	0.014	0.32	1	-10000	0	1
S1PR2	0.02	0.005	-10000	0	-10000	0	0
EDG1	0	0	-10000	0	-10000	0	0
S1P1/S1P	0	0.028	-10000	0	-0.23	3	3
S1PR5	0.001	0.081	0.32	1	-0.33	29	30
S1PR4	0.007	0.064	-10000	0	-0.33	18	18
GNAI1	0.02	0.016	-10000	0	-0.33	1	1
S1P/S1P5/G12	0.017	0.051	0.22	1	-0.17	22	23
S1P/S1P3/Gq	0.004	0.067	-10000	0	-0.28	22	22
S1P/S1P4/Gi	-0.013	0.083	-10000	0	-0.34	13	13
GNAQ	0.02	0.016	-10000	0	-0.33	1	1
GNAZ	-0.006	0.092	-10000	0	-0.33	39	39
GNA14	0.013	0.05	-10000	0	-0.33	11	11
GNA15	0.02	0.006	-10000	0	-10000	0	0
GNA12	0.019	0.007	-10000	0	-10000	0	0
GNA13	0.02	0.004	-10000	0	-10000	0	0
GNA11	0.019	0.016	-10000	0	-0.33	1	1
ABCC1	0.021	0.003	-10000	0	-10000	0	0

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	0.031	0.063	0.22	1	-0.25	14	15
Ran/GTP/Exportin 1/HDAC1	-0.018	0.004	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.008	0.064	-10000	0	-0.28	16	16
SUMO1	0.021	0.003	-10000	0	-10000	0	0
ZFPM1	0.021	0.014	0.32	1	-10000	0	1
NPC/RanGAP1/SUMO1/Ubc9	0.006	0.002	-10000	0	-10000	0	0
FKBP3	0.02	0.004	-10000	0	-10000	0	0
Histones	0.034	0.053	-10000	0	-0.3	2	2
YY1/LSF	0.013	0.046	-10000	0	-0.24	8	8
SMG5	0.018	0.008	-10000	0	-10000	0	0
RAN	0.021	0.014	0.32	1	-10000	0	1
I kappa B alpha/HDAC3	0.007	0.032	-10000	0	-0.2	11	11
I kappa B alpha/HDAC1	0.014	0.04	-10000	0	-0.32	1	1
SAP18	0.02	0.005	-10000	0	-10000	0	0
RELA	0.008	0.044	-10000	0	-0.22	11	11
HDAC1/Smad7	0.036	0.019	-10000	0	-0.2	1	1
RANGAP1	0.02	0.004	-10000	0	-10000	0	0
HDAC3/TR2	0.015	0.049	-10000	0	-0.32	2	2
NuRD/MBD3 Complex	-0.005	0.054	-10000	0	-0.29	10	10
NF kappa B1 p50/RelA	0.012	0.069	-10000	0	-0.28	15	15
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	-0.006	0.093	-10000	0	-0.33	40	40
GATA1	-0.014	0.1	-10000	0	-0.33	50	50
Mad/Max	0.03	0.007	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	-0.018	0.093	-10000	0	-0.31	26	26
RBBP7	0.02	0.004	-10000	0	-10000	0	0
NPC	0.013	0.001	-10000	0	-10000	0	0
RBBP4	0.021	0.003	-10000	0	-10000	0	0
MAX	0.02	0.004	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.02	0.005	-10000	0	-10000	0	0
NFKBIA	0.007	0.023	-10000	0	-10000	0	0
KAT2B	0.02	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	-0.008	0.051	-10000	0	-0.37	3	3
SIN3 complex	0.047	0.019	-10000	0	-10000	0	0
SMURF1	0.02	0.005	-10000	0	-10000	0	0
CHD3	0.02	0.006	-10000	0	-10000	0	0
SAP30	0.021	0.004	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.02	0.006	-10000	0	-10000	0	0
YY1/HDAC3	0.005	0.048	-10000	0	-0.27	9	9
YY1/HDAC2	0.013	0.043	-10000	0	-0.24	8	8
YY1/HDAC1	0.013	0.046	-10000	0	-0.24	8	8
NuRD/MBD2 Complex (MeCP1)	-0.008	0.058	-10000	0	-0.31	10	10
PPARG	-0.022	0.1	-10000	0	-0.29	60	60
HDAC8/hEST1B	0.035	0.017	-10000	0	-10000	0	0
UBE2I	0.021	0.004	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.02	0.005	-10000	0	-10000	0	0
TNFRSF1A	0.02	0.005	-10000	0	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.016	0.048	-10000	0	-0.32	2	2
MBD3L2	0.016	0.004	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.035	0.019	-10000	0	-0.2	1	1
CREBBP	0.021	0.004	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	-0.002	0.081	-10000	0	-0.3	26	26
HDAC1	0.021	0.002	-10000	0	-10000	0	0
HDAC3	0.007	0.027	-10000	0	-0.16	12	12
HDAC2	0.019	0.006	-10000	0	-10000	0	0
YY1	0.008	0.003	-10000	0	-10000	0	0
HDAC8	0.021	0.002	-10000	0	-10000	0	0
SMAD7	0.018	0.017	-10000	0	-0.33	1	1
NCOR2	0.021	0.003	-10000	0	-10000	0	0
MXD1	0.021	0.002	-10000	0	-10000	0	0
STAT3	0.011	0.003	-10000	0	-10000	0	0
NFKB1	0.021	0.003	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.021	0.002	-10000	0	-10000	0	0
YY1/LSF/HDAC1	0.024	0.047	-10000	0	-0.22	8	8
YY1/SAP30/HDAC1	0.023	0.046	-10000	0	-0.22	8	8
EP300	0.02	0.005	-10000	0	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.011	0.003	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.007	0.023	-10000	0	-10000	0	0
histone deacetylation	0	0.062	-10000	0	-0.31	10	10
STAT3 (dimer non-phopshorylated)/HDAC3	0.006	0.038	-10000	0	-0.22	7	7
nuclear export	-0.035	0.017	-10000	0	-10000	0	0
PRKACA	0.02	0.005	-10000	0	-10000	0	0
GATAD2B	0.018	0.008	-10000	0	-10000	0	0
GATAD2A	0.02	0.005	-10000	0	-10000	0	0
GATA2/HDAC3	0.003	0.067	-10000	0	-0.19	41	41
GATA1/HDAC1	0.004	0.077	-10000	0	-0.23	50	50
GATA1/HDAC3	-0.001	0.072	-10000	0	-0.31	8	8
CHD4	0.02	0.005	-10000	0	-10000	0	0
TNF-alpha/TNFR1A	0.022	0.044	0.23	1	-0.23	14	15
SIN3/HDAC complex/Mad/Max	-0.008	0.057	-10000	0	-0.29	9	9
NuRD Complex	-0.003	0.076	-10000	0	-0.3	20	20
positive regulation of chromatin silencing	0.032	0.051	-10000	0	-0.29	2	2
SIN3B	0.02	0.005	-10000	0	-10000	0	0
MTA2	0.021	0.003	-10000	0	-10000	0	0
SIN3A	0.021	0.003	-10000	0	-10000	0	0
XPO1	0.021	0.002	-10000	0	-10000	0	0
SUMO1/HDAC1	0.027	0.031	-10000	0	-0.21	3	3
HDAC complex	0.048	0.019	-10000	0	-10000	0	0
GATA1/Fog1	0.004	0.076	-10000	0	-0.22	50	50
FKBP25/HDAC1/HDAC2	0.037	0.015	-10000	0	-10000	0	0
TNF	0.011	0.06	0.32	1	-0.33	15	16
negative regulation of cell growth	-0.007	0.058	-10000	0	-0.29	9	9
NuRD/MBD2/PRMT5 Complex	-0.008	0.058	-10000	0	-0.31	10	10
Ran/GTP/Exportin 1	0.027	0.031	-10000	0	-0.19	4	4
NF kappa B/RelA/I kappa B alpha	-0.001	0.055	-10000	0	-0.28	14	14
SIN3/HDAC complex/NCoR1	-0.01	0.072	-10000	0	-0.35	14	14
TFCP2	0.021	0.003	-10000	0	-10000	0	0
NR2C1	0.021	0.003	-10000	0	-10000	0	0
MBD3	0.018	0.022	-10000	0	-0.33	2	2
MBD2	0.019	0.007	-10000	0	-10000	0	0

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.001	0.062	-10000	0	-0.42	2	2
UGCG	-0.002	0.11	-10000	0	-0.62	15	15
AKT1/mTOR/p70S6K/Hsp90/TERT	0.052	0.084	0.27	9	-0.35	6	15
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.002	0.11	-10000	0	-0.61	15	15
mol:DAG	0.002	0.081	-10000	0	-0.79	5	5
CaM/Ca2+/Calcineurin A alpha-beta B1	0.024	0.078	0.29	2	-0.36	8	10
FRAP1	0.018	0.086	0.31	2	-0.4	8	10
FOXO3	0.014	0.081	0.31	1	-0.41	7	8
AKT1	0.017	0.087	0.29	2	-0.44	7	9
GAB2	0.017	0.035	-10000	0	-0.33	5	5
SMPD1	0.006	0.083	-10000	0	-0.6	9	9
SGMS1	0.011	0.059	-10000	0	-0.56	5	5
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
mol:GDP	-0.012	0.009	-10000	0	-0.19	1	1
CALM1	0.02	0.005	-10000	0	-10000	0	0
cell proliferation	0.024	0.088	0.29	2	-0.42	8	10
EIF3A	0.021	0.002	-10000	0	-10000	0	0
PI3K	0.029	0.015	-10000	0	-0.23	1	1
RPS6KB1	0.014	0.059	-10000	0	-0.84	2	2
mol:sphingomyelin	0.002	0.081	-10000	0	-0.79	5	5
natural killer cell activation	0	0.001	-10000	0	-10000	0	0
JAK3	0.02	0.006	-10000	0	-10000	0	0
PIK3R1	0.02	0.016	-10000	0	-0.32	1	1
JAK1	0.021	0.005	-10000	0	-10000	0	0
NFKB1	0.021	0.003	-10000	0	-10000	0	0
MYC	0.04	0.12	0.4	5	-0.76	3	8
MYB	0.002	0.11	-10000	0	-1	5	5
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.016	0.067	-10000	0	-0.36	5	5
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.034	0.058	-10000	0	-0.77	2	2
mol:PI-3-4-5-P3	0.016	0.068	-10000	0	-0.34	6	6
Rac1/GDP	-0.014	0.01	-10000	0	-0.17	1	1
T cell proliferation	0.011	0.067	-10000	0	-0.31	5	5
SHC1	0.019	0.016	0.32	1	-10000	0	1
RAC1	0.019	0.007	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.001	0.009	0.088	3	-0.066	4	7
PRKCZ	0.011	0.066	-10000	0	-0.31	4	4
NF kappa B1 p50/RelA	0.033	0.083	0.3	2	-0.36	8	10
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0	0.054	-10000	0	-0.35	6	6
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
RELA	0.021	0.004	-10000	0	-10000	0	0
IL2RA	0.04	0.079	0.32	35	-0.33	1	36
IL2RB	0.019	0.022	-10000	0	-0.32	2	2
TERT	0.08	0.13	0.32	108	-10000	0	108
E2F1	0.011	0.078	0.24	2	-0.44	12	14
SOS1	0.021	0.004	-10000	0	-10000	0	0
RPS6	0.019	0.006	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.005	0.031	4	-0.047	3	7
PTPN11	0.021	0.005	-10000	0	-10000	0	0
IL2RG	0.018	0.034	-10000	0	-0.33	5	5
actin cytoskeleton organization	0.011	0.067	-10000	0	-0.31	5	5
GRB2	0.02	0.005	-10000	0	-10000	0	0
IL2	0.02	0.005	-10000	0	-10000	0	0
PIK3CA	0.021	0.006	-10000	0	-10000	0	0
Rac1/GTP	0.032	0.019	-10000	0	-0.16	1	1
LCK	0.021	0.026	0.32	1	-0.32	2	3
BCL2	0.016	0.084	0.47	1	-0.6	2	3

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.018	0.031	-10000	0	-0.33	4	4
HRAS	0.021	0.004	-10000	0	-10000	0	0
EGFR	0.014	0.045	0.32	1	-0.33	8	9
AKT	0.029	0.064	0.24	10	-0.22	4	14
FOXO3	0.019	0.006	-10000	0	-10000	0	0
AKT1	0.02	0.005	-10000	0	-10000	0	0
FOXO1	0.02	0.005	-10000	0	-10000	0	0
AKT3	0.017	0.027	-10000	0	-0.33	3	3
FOXO4	0.021	0.002	-10000	0	-10000	0	0
MET	0.011	0.072	0.32	6	-0.33	18	24
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
PIK3CB	0.021	0.003	-10000	0	-10000	0	0
NRAS	0.02	0.005	-10000	0	-10000	0	0
PIK3CG	0.01	0.059	-10000	0	-0.33	15	15
PIK3R3	0.02	0.015	-10000	0	-0.33	1	1
PIK3R2	0.02	0.005	-10000	0	-10000	0	0
NF1	0.021	0.004	-10000	0	-10000	0	0
RAS	0.017	0.042	0.19	6	-0.13	14	20
ERBB2	0.021	0.004	-10000	0	-10000	0	0
proliferation/survival/translation	-0.011	0.075	0.29	17	-0.21	1	18
PI3K	0.02	0.062	0.21	23	-0.16	14	37
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
KRAS	0.02	0.006	-10000	0	-10000	0	0
FOXO	0.047	0.049	0.23	12	-10000	0	12
AKT2	0.02	0.005	-10000	0	-10000	0	0
PTEN	0.021	0.003	-10000	0	-10000	0	0

IGF1 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
NCK2	0.021	0.002	-10000	0	-10000	0	0
PTK2	0.018	0.007	-10000	0	-10000	0	0
CRKL	-0.018	0.026	0.15	2	-0.19	8	10
GRB2/SOS1/SHC	0.035	0.017	-10000	0	-10000	0	0
HRAS	0.021	0.004	-10000	0	-10000	0	0
IRS1/Crk	0.009	0.032	0.11	1	-0.18	11	12
IGF-1R heterotetramer/IGF1/PTP1B	0.034	0.034	0.21	1	-0.19	9	10
AKT1	-0.023	0.039	0.15	11	-0.18	7	18
BAD	-0.026	0.037	0.14	11	-0.23	1	12
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.018	0.027	0.15	2	-0.19	9	11
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.018	0.036	0.19	4	-0.19	11	15
RAF1	-0.018	0.074	0.26	1	-0.4	14	15
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.041	0.037	0.2	1	-0.19	7	8
YWHAZ	0.019	0.007	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.021	0.035	0.2	1	-0.2	11	12
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
RPS6KB1	-0.022	0.039	0.15	13	-0.18	6	19
GNB2L1	0.02	0.004	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.007	0.071	0.27	6	-0.36	4	10
PXN	0.021	0.003	-10000	0	-10000	0	0
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.03	0.007	-10000	0	-10000	0	0
HRAS/GTP	-0.023	0.016	-10000	0	-0.17	2	2
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.048	0.032	-10000	0	-0.16	2	2
IGF-1R heterotetramer	0.02	0.015	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	0.032	0.039	0.2	1	-0.19	11	12
Crk/p130 Cas/Paxillin	0.036	0.039	0.2	1	-0.18	11	12
IGF1R	0.02	0.016	-10000	0	-10000	0	0
IGF1	0.014	0.056	0.33	1	-0.35	11	12
IRS2/Crk	-0.021	0.028	0.14	2	-0.18	10	12
PI3K	0.039	0.041	0.2	1	-0.18	11	12
apoptosis	0.023	0.041	0.21	1	-0.28	1	2
HRAS/GDP	0.015	0.003	-10000	0	-10000	0	0
PRKCD	-0.003	0.04	-10000	0	-0.24	9	9
RAF1/14-3-3 E	-0.013	0.075	0.25	2	-0.35	14	16
BAD/14-3-3	-0.024	0.043	0.28	1	-0.22	1	2
PRKCZ	-0.024	0.04	0.15	11	-0.18	7	18
Crk/p130 Cas/Paxillin/FAK1	-0.032	0.032	-10000	0	-0.22	1	1
PTPN1	0.02	0.005	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0	0.043	-10000	0	-0.26	8	8
BCAR1	0.02	0.016	-10000	0	-0.33	1	1
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.038	0.032	0.21	1	-0.16	4	5
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.021	0.003	-10000	0	-10000	0	0
IRS1/NCK2	0.016	0.036	-10000	0	-0.19	11	11
GRB10	0.019	0.006	-10000	0	-10000	0	0
PTPN11	-0.019	0.03	0.15	3	-0.19	11	14
IRS1	-0.015	0.033	0.12	8	-0.2	11	19
IRS2	-0.018	0.029	0.15	3	-0.19	10	13
IGF-1R heterotetramer/IGF1	0.024	0.043	0.23	1	-0.25	11	12
GRB2	0.02	0.004	-10000	0	-10000	0	0
PDPK1	-0.021	0.041	0.16	12	-0.18	9	21
YWHAE	0.019	0.006	-10000	0	-10000	0	0
PRKD1	-0.006	0.044	-10000	0	-0.29	5	5
SHC1	0.018	0.016	0.32	1	-10000	0	1

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	0.048	0.021	-10000	0	-0.18	1	1
HDAC3	0.02	0.004	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.018	0.005	-10000	0	-10000	0	0
GATA1/HDAC4	0.005	0.076	-10000	0	-0.23	49	49
GATA1/HDAC5	0.004	0.076	-10000	0	-0.23	49	49
GATA2/HDAC5	0.01	0.07	-10000	0	-0.23	40	40
HDAC5/BCL6/BCoR	0.039	0.013	-10000	0	-10000	0	0
HDAC9	0.019	0.046	0.32	5	-0.33	5	10
Glucocorticoid receptor/Hsp90/HDAC6	0.039	0.013	-10000	0	-10000	0	0
HDAC4/ANKRA2	0.03	0.008	-10000	0	-10000	0	0
HDAC5/YWHAB	0.029	0.009	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.006	0.002	-10000	0	-10000	0	0
GATA2	-0.006	0.093	-10000	0	-0.33	40	40
HDAC4/RFXANK	0.029	0.008	-10000	0	-10000	0	0
BCOR	0.021	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.019	0.016	-10000	0	-0.33	1	1
HDAC5	0.021	0.004	-10000	0	-10000	0	0
GNB1/GNG2	0.028	0.018	-10000	0	-0.23	2	2
Histones	0.009	0.05	-10000	0	-0.2	17	17
ADRBK1	0.021	0.004	-10000	0	-10000	0	0
HDAC4	0.021	0.003	-10000	0	-10000	0	0
XPO1	0.021	0.002	-10000	0	-10000	0	0
HDAC5/ANKRA2	0.03	0.008	-10000	0	-10000	0	0
HDAC4/Ubc9	0.03	0.007	-10000	0	-10000	0	0
HDAC7	0.021	0.003	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.028	0.01	-10000	0	-10000	0	0
TUBA1B	0.021	0.003	-10000	0	-10000	0	0
HDAC6	0.021	0.004	-10000	0	-10000	0	0
HDAC5/RFXANK	0.029	0.008	-10000	0	-10000	0	0
CAMK4	0.016	0.043	0.32	1	-0.33	7	8
Tubulin/HDAC6	0.044	0.03	0.22	12	-10000	0	12
SUMO1	0.021	0.003	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.02	0.005	-10000	0	-10000	0	0
GATA1	-0.014	0.1	-10000	0	-0.33	50	50
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.019	0.006	-10000	0	-10000	0	0
NR3C1	0.021	0.004	-10000	0	-10000	0	0
SUMO1/HDAC4	0.027	0.03	-10000	0	-0.2	3	3
SRF	0.02	0.004	-10000	0	-10000	0	0
HDAC4/YWHAB	0.029	0.009	-10000	0	-10000	0	0
Tubulin	0.035	0.033	0.23	13	-10000	0	13
HDAC4/14-3-3 E	0.028	0.01	-10000	0	-10000	0	0
GNB1	0.021	0.004	-10000	0	-10000	0	0
RANGAP1	0.02	0.004	-10000	0	-10000	0	0
BCL6/BCoR	0.029	0.008	-10000	0	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0.04	0.012	-10000	0	-10000	0	0
HDAC4/SRF	0.036	0.031	0.22	1	-0.2	7	8
HDAC4/ER alpha	0.027	0.042	0.23	8	-0.23	8	16
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.009	0.05	-10000	0	-0.19	17	17
cell motility	0.044	0.03	0.22	12	-10000	0	12
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.021	0.004	-10000	0	-10000	0	0
HDAC7/HDAC3	0.03	0.007	-10000	0	-10000	0	0
BCL6	0.02	0.004	-10000	0	-10000	0	0
HDAC4/CaMK II delta B	0.021	0.003	-10000	0	-10000	0	0
Hsp90/HDAC6	0.029	0.008	-10000	0	-10000	0	0
ESR1	0.019	0.059	0.32	9	-0.33	8	17
HDAC6/HDAC11	0.03	0.008	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.027	0.031	-10000	0	-0.19	4	4
NPC	0.013	0.001	-10000	0	-10000	0	0
MEF2C	0.02	0.005	-10000	0	-10000	0	0
RAN	0.021	0.014	0.32	1	-10000	0	1
HDAC4/MEF2C	0.056	0.022	-10000	0	-10000	0	0
GNG2	0.019	0.022	-10000	0	-0.33	2	2
NCOR2	0.021	0.003	-10000	0	-10000	0	0
TUBB2A	0.029	0.05	0.32	14	-10000	0	14
HDAC11	0.02	0.004	-10000	0	-10000	0	0
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
RANBP2	0.021	0.002	-10000	0	-10000	0	0
ANKRA2	0.02	0.004	-10000	0	-10000	0	0
RFXANK	0.02	0.005	-10000	0	-10000	0	0
nuclear import	-0.021	0.011	-10000	0	-0.17	1	1

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	-0.018	0.007	-10000	0	-10000	0	0
SNTA1	0.022	0.024	0.32	3	-10000	0	3
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	-0.016	0.028	0.3	3	-10000	0	3
MAPK12	-0.009	0.015	-10000	0	-0.17	2	2
CCND1	-0.003	0.051	-10000	0	-0.38	9	9
p38 gamma/SNTA1	-0.008	0.043	0.18	18	-0.16	2	20
MAP2K3	0.02	0.006	-10000	0	-10000	0	0
PKN1	0.02	0.005	-10000	0	-10000	0	0
G2/M transition checkpoint	-0.009	0.015	-10000	0	-0.17	2	2
MAP2K6	-0.004	0.018	-10000	0	-0.18	2	2
MAPT	-0.007	0.071	0.22	11	-0.25	25	36
MAPK13	-0.015	0.005	-10000	0	-10000	0	0
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.004	0.001	-10000	0	-10000	0	0

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.005	0.069	-10000	0	-0.34	13	13
KLHL20	-0.002	0.051	0.16	2	-0.21	11	13
CYFIP2	0.016	0.04	-10000	0	-0.33	7	7
Rac1/GDP	-0.011	0.06	0.33	3	-0.26	6	9
ENAH	-0.005	0.07	-10000	0	-0.35	13	13
AP1M1	0.02	0.005	-10000	0	-10000	0	0
RAP1B	0.02	0.005	-10000	0	-10000	0	0
RAP1A	0.02	0.004	-10000	0	-10000	0	0
CTNNB1	0.021	0.004	-10000	0	-10000	0	0
CDC42/GTP	-0.026	0.022	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.015	0.027	-10000	0	-0.14	15	15
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.046	0.026	-10000	0	-0.18	3	3
RAPGEF1	-0.009	0.058	-10000	0	-0.32	8	8
CTNND1	0.021	0.003	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.002	0.072	-10000	0	-0.36	13	13
CRK	-0.009	0.051	-10000	0	-0.34	8	8
E-cadherin/gamma catenin/alpha catenin	0.039	0.019	-10000	0	-0.2	2	2
alphaE/beta7 Integrin	0.028	0.015	-10000	0	-0.23	1	1
IQGAP1	0.021	0.003	-10000	0	-10000	0	0
NCKAP1	0.021	0.003	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.034	0.016	-10000	0	-10000	0	0
DLG1	-0.003	0.066	-10000	0	-0.35	12	12
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.025	0.016	-10000	0	-10000	0	0
MLLT4	0.019	0.006	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.047	0.054	0.21	39	-0.16	7	46
PI3K	-0.031	0.019	-10000	0	-10000	0	0
ARF6	0.02	0.004	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
E-cadherin/gamma catenin	0.029	0.018	-10000	0	-0.23	2	2
TIAM1	0.015	0.043	-10000	0	-0.33	8	8
E-cadherin(dimer)/Ca2+	0.045	0.02	-10000	0	-0.16	2	2
AKT1	-0.017	0.026	-10000	0	-10000	0	0
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
CDH1	0.019	0.022	-10000	0	-0.33	2	2
RhoA/GDP	-0.011	0.064	0.3	4	-0.25	7	11
actin cytoskeleton organization	0.002	0.044	0.16	9	-0.16	10	19
CDC42/GDP	-0.011	0.064	0.3	4	-0.26	7	11
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.009	0.013	-10000	0	-0.19	2	2
ITGB7	0.02	0.016	-10000	0	-0.33	1	1
RAC1	0.019	0.007	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.049	0.021	-10000	0	-0.17	2	2
E-cadherin/Ca2+/beta catenin/alpha catenin	0.034	0.016	-10000	0	-0.16	2	2
mol:GDP	-0.012	0.069	0.32	4	-0.29	9	13
CDC42/GTP/IQGAP1	0.028	0.006	-10000	0	-10000	0	0
JUP	0.021	0.004	-10000	0	-10000	0	0
p120 catenin/RhoA/GDP	0.006	0.06	0.23	2	-0.26	5	7
RAC1/GTP/IQGAP1	0.025	0.01	-10000	0	-10000	0	0
PIP5K1C/AP1M1	0.029	0.008	-10000	0	-10000	0	0
RHOA	0.02	0.004	-10000	0	-10000	0	0
CDC42	0.021	0.003	-10000	0	-10000	0	0
CTNNA1	0.02	0.004	-10000	0	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.003	0.038	0.14	12	-0.15	5	17
NME1	0.047	0.085	0.32	44	-10000	0	44
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	0.001	0.055	-10000	0	-0.34	8	8
regulation of cell-cell adhesion	-0.024	0.019	-10000	0	-10000	0	0
WASF2	-0.004	0.023	-10000	0	-0.093	1	1
Rap1/GTP	-0.023	0.03	-10000	0	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.051	0.03	-10000	0	-0.18	3	3
CCND1	0.002	0.042	0.14	9	-0.17	7	16
VAV2	-0.01	0.13	-10000	0	-0.57	20	20
RAP1/GDP	-0.019	0.045	0.19	1	-0.23	3	4
adherens junction assembly	0.001	0.054	-10000	0	-0.33	8	8
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.021	0.004	-10000	0	-10000	0	0
PIP5K1C	0.02	0.005	-10000	0	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.036	0.027	-10000	0	-0.17	2	2
E-cadherin/beta catenin	0.004	0.02	-10000	0	-0.28	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	-0.005	0.069	-10000	0	-0.35	13	13
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
Rac1/GTP	-0.007	0.067	-10000	0	-0.32	16	16
E-cadherin/beta catenin/alpha catenin	0.039	0.019	-10000	0	-0.18	2	2
ITGAE	0.02	0.006	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.002	0.073	-10000	0	-0.36	13	13

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	-0.005	0.044	0.3	2	-0.24	7	9
adherens junction organization	-0.005	0.054	-10000	0	-0.41	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.013	0.051	0.18	5	-0.24	2	7
FMN1	-0.008	0.055	-10000	0	-0.3	9	9
mol:IP3	-0.013	0.03	-10000	0	-0.21	4	4
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.001	0.057	-10000	0	-0.28	14	14
CTNNB1	0.021	0.004	-10000	0	-10000	0	0
AKT1	-0.014	0.039	0.2	2	-0.24	5	7
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.002	0.11	-10000	0	-0.71	8	8
CTNND1	0.021	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.004	0.044	-10000	0	-0.28	9	9
VASP	-0.001	0.043	-10000	0	-0.32	6	6
ZYX	-0.006	0.053	-10000	0	-0.34	7	7
JUB	-0.002	0.054	-10000	0	-0.27	14	14
EGFR(dimer)	0.006	0.061	0.2	1	-0.31	9	10
E-cadherin/beta catenin-gamma catenin	0.039	0.018	-10000	0	-0.16	2	2
mol:PI-3-4-5-P3	0.02	0.05	0.22	2	-0.26	5	7
PIK3CA	0.019	0.009	-10000	0	-10000	0	0
PI3K	0.021	0.051	0.23	2	-0.26	5	7
FYN	-0.014	0.064	0.33	2	-0.26	10	12
mol:Ca2+	-0.013	0.029	-10000	0	-0.2	4	4
JUP	0.021	0.004	-10000	0	-10000	0	0
PIK3R1	0.019	0.017	-10000	0	-0.33	1	1
mol:DAG	-0.013	0.03	-10000	0	-0.21	4	4
CDH1	0.019	0.022	-10000	0	-0.32	2	2
RhoA/GDP	-0.004	0.064	0.18	5	-0.25	1	6
establishment of polarity of embryonic epithelium	-0.001	0.042	-10000	0	-0.31	6	6
SRC	0.02	0.004	-10000	0	-10000	0	0
RAC1	0.019	0.007	-10000	0	-10000	0	0
RHOA	0.02	0.004	-10000	0	-10000	0	0
EGFR	0.014	0.045	0.32	1	-0.33	8	9
CASR	-0.007	0.045	0.3	2	-0.2	4	6
RhoA/GTP	0.01	0.038	-10000	0	-0.2	3	3
AKT2	-0.013	0.038	0.2	2	-0.24	5	7
actin cable formation	-0.012	0.046	-10000	0	-0.32	6	6
apoptosis	-0.002	0.053	0.26	8	-0.25	5	13
CTNNA1	0.02	0.006	-10000	0	-10000	0	0
mol:GDP	-0.014	0.041	0.17	4	-0.21	5	9
PIP5K1A	-0.004	0.045	-10000	0	-0.28	9	9
PLCG1	-0.013	0.03	-10000	0	-0.21	4	4
Rac1/GTP	0.013	0.058	-10000	0	-0.31	7	7
homophilic cell adhesion	-0.001	0.002	-10000	0	-10000	0	0

Circadian rhythm 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
chromatin modification	0.045	0.054	0.41	5	-10000	0	5
CLOCK	0.022	0.004	-10000	0	-10000	0	0
TIMELESS/CRY2	0.026	0.031	-10000	0	-10000	0	0
DEC1/BMAL1	0.028	0.008	-10000	0	-10000	0	0
ATR	0.021	0.003	-10000	0	-10000	0	0
NR1D1	0.008	0.02	-10000	0	-10000	0	0
ARNTL	0.021	0.005	-10000	0	-10000	0	0
TIMELESS	0.01	0.036	0.37	2	-10000	0	2
NPAS2	0.024	0.023	0.32	3	-10000	0	3
CRY2	0.021	0.003	-10000	0	-10000	0	0
mol:CO	-0.004	0.012	-10000	0	-0.1	7	7
CHEK1	0.037	0.07	0.32	29	-10000	0	29
mol:HEME	0.004	0.012	0.1	7	-10000	0	7
PER1	0.008	0.062	-10000	0	-0.33	17	17
BMAL/CLOCK/NPAS2	0.046	0.022	0.23	3	-10000	0	3
BMAL1/CLOCK	0.01	0.042	-10000	0	-10000	0	0
S phase of mitotic cell cycle	0.045	0.054	0.41	5	-10000	0	5
TIMELESS/CHEK1/ATR	0.045	0.055	0.42	5	-10000	0	5
mol:NADPH	0.004	0.012	0.1	7	-10000	0	7
PER1/TIMELESS	0.019	0.041	-10000	0	-10000	0	0
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.018	0.004	-10000	0	-10000	0	0

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.01	0.014	-10000	0	-10000	0	0
regulation of axonogenesis	-0.001	0.016	0.25	2	-10000	0	2
myoblast fusion	-0.012	0.021	-10000	0	-10000	0	0
mol:GTP	0.015	0.015	-10000	0	-0.16	3	3
regulation of calcium-dependent cell-cell adhesion	-0.046	0.057	0.2	5	-0.21	38	43
ARF1/GTP	0.024	0.018	-10000	0	-10000	0	0
mol:GM1	0.005	0.01	-10000	0	-10000	0	0
mol:Choline	-0.01	0.009	-10000	0	-10000	0	0
lamellipodium assembly	0.005	0.028	-10000	0	-0.34	2	2
MAPK3	0.011	0.012	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.047	0.058	0.22	38	-0.2	5	43
ARF1	0.02	0.006	-10000	0	-10000	0	0
ARF6/GDP	0.012	0.021	-10000	0	-10000	0	0
ARF1/GDP	0.014	0.029	-10000	0	-0.21	3	3
ARF6	0.026	0.008	-10000	0	-10000	0	0
RAB11A	0.021	0.003	-10000	0	-10000	0	0
TIAM1	0.014	0.043	-10000	0	-0.32	8	8
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.012	0.01	-10000	0	-10000	0	0
actin filament bundle formation	-0.018	0.029	0.21	3	-10000	0	3
KALRN	0.004	0.016	-10000	0	-0.18	2	2
RAB11FIP3/RAB11A	0.03	0.007	-10000	0	-10000	0	0
RhoA/GDP	0.018	0.029	-10000	0	-0.21	3	3
NME1	0.045	0.086	0.32	44	-10000	0	44
Rac1/GDP	0.017	0.028	-10000	0	-0.23	1	1
substrate adhesion-dependent cell spreading	0.015	0.015	-10000	0	-0.16	3	3
cortical actin cytoskeleton organization	0.005	0.028	-10000	0	-0.34	2	2
RAC1	0.019	0.007	-10000	0	-10000	0	0
liver development	0.015	0.015	-10000	0	-0.16	3	3
ARF6/GTP	0.015	0.015	-10000	0	-0.16	3	3
RhoA/GTP	0.025	0.018	-10000	0	-10000	0	0
mol:GDP	0.005	0.017	-10000	0	-0.21	2	2
ARF6/GTP/RAB11FIP3/RAB11A	0.037	0.019	-10000	0	-10000	0	0
RHOA	0.02	0.004	-10000	0	-10000	0	0
PLD1	0.01	0.013	-10000	0	-10000	0	0
RAB11FIP3	0.021	0.004	-10000	0	-10000	0	0
tube morphogenesis	0.005	0.028	-10000	0	-0.34	2	2
ruffle organization	0.001	0.016	-10000	0	-0.25	2	2
regulation of epithelial cell migration	0.015	0.015	-10000	0	-0.16	3	3
PLD2	0.01	0.012	-10000	0	-10000	0	0
PIP5K1A	0.001	0.016	-10000	0	-0.25	2	2
mol:Phosphatidic acid	-0.01	0.009	-10000	0	-10000	0	0
Rac1/GTP	0.005	0.028	-10000	0	-0.34	2	2

Class I PI3K signaling events mediated by Akt

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
BCL2L1	-0.015	0.005	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.025	0.013	-10000	0	-10000	0	0
CDKN1B	0.008	0.044	-10000	0	-0.29	7	7
CDKN1A	0.007	0.045	-10000	0	-0.29	8	8
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.019	0.006	-10000	0	-10000	0	0
FOXO3	0.008	0.034	-10000	0	-0.29	4	4
AKT1	0.001	0.038	-10000	0	-0.3	8	8
BAD	0.021	0.003	-10000	0	-10000	0	0
AKT3	0.006	0.016	-10000	0	-0.25	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.007	0.044	-10000	0	-0.29	8	8
AKT1/ASK1	0.023	0.053	-10000	0	-0.26	10	10
BAD/YWHAZ	0.035	0.017	-10000	0	-10000	0	0
RICTOR	0.017	0.008	-10000	0	-10000	0	0
RAF1	0.02	0.004	-10000	0	-10000	0	0
JNK cascade	-0.022	0.052	0.25	10	-10000	0	10
TSC1	0.007	0.036	-10000	0	-0.29	5	5
YWHAZ	0.019	0.007	-10000	0	-10000	0	0
AKT1/RAF1	0.028	0.058	0.22	2	-0.28	9	11
EP300	0.02	0.005	-10000	0	-10000	0	0
mol:GDP	0.003	0.039	-10000	0	-0.29	8	8
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.005	0.042	-10000	0	-0.29	8	8
YWHAQ	0.021	0.003	-10000	0	-10000	0	0
TBC1D4	-0.006	0.002	-10000	0	-10000	0	0
MAP3K5	0.019	0.006	-10000	0	-10000	0	0
MAPKAP1	0.021	0.004	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.017	0.067	0.27	10	-0.22	8	18
YWHAH	0.02	0.004	-10000	0	-10000	0	0
AKT1S1	0.007	0.042	-10000	0	-0.29	7	7
CASP9	0.008	0.041	-10000	0	-0.29	6	6
YWHAB	0.02	0.005	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.029	0.063	0.26	7	-0.28	8	15
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.039	0.013	-10000	0	-10000	0	0
YWHAE	0.019	0.006	-10000	0	-10000	0	0
SRC	0.02	0.004	-10000	0	-10000	0	0
AKT2/p21CIP1	0.009	0.049	0.21	9	-0.25	8	17
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.008	0.036	0.18	1	-0.32	4	5
CHUK	0.006	0.043	-10000	0	-0.29	8	8
BAD/BCL-XL	0.025	0.054	-10000	0	-0.28	8	8
mTORC2	0.022	0.011	-10000	0	-10000	0	0
AKT2	0.007	0.002	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.018	0.082	0.3	5	-0.35	9	14
PDPK1	0.021	0.003	-10000	0	-10000	0	0
MDM2	0.015	0.055	-10000	0	-0.29	7	7
MAPKKK cascade	-0.028	0.057	0.27	9	-0.22	2	11
MDM2/Cbp/p300	0.044	0.07	0.3	5	-0.28	7	12
TSC1/TSC2	0.004	0.05	0.25	8	-0.28	8	16
proteasomal ubiquitin-dependent protein catabolic process	0.042	0.067	0.29	5	-0.26	8	13
glucose import	-0.009	0.023	0.2	4	-0.17	4	8
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.01	0.037	-10000	0	-0.2	7	7
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.011	0.014	-10000	0	-0.17	4	4
GSK3A	0.007	0.045	-10000	0	-0.29	8	8
FOXO1	0.006	0.037	-10000	0	-0.29	6	6
GSK3B	0.006	0.041	-10000	0	-0.29	7	7
SFN	0.025	0.043	0.32	9	-0.33	1	10
G1/S transition of mitotic cell cycle	0.005	0.052	0.23	4	-0.28	8	12
p27Kip1/14-3-3 family	0.012	0.055	-10000	0	-0.33	8	8
PRKACA	0.02	0.005	-10000	0	-10000	0	0
KPNA1	0.021	0.003	-10000	0	-10000	0	0
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
YWHAG	0.02	0.004	-10000	0	-10000	0	0
RHEB	0.02	0.005	-10000	0	-10000	0	0
CREBBP	0.021	0.004	-10000	0	-10000	0	0

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.02	0.004	-10000	0	-10000	0	0
mol:S1P	0	0.002	-10000	0	-10000	0	0
S1P1/S1P/Gi	-0.01	0.062	-10000	0	-0.19	51	51
GNAO1	0.022	0.035	0.32	4	-0.33	2	6
S1P/S1P3/G12/G13	0.034	0.017	-10000	0	-10000	0	0
AKT1	0.004	0.07	-10000	0	-0.4	13	13
AKT3	-0.005	0.1	-10000	0	-0.86	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.02	0.004	-10000	0	-10000	0	0
GNAI2	0.02	0.007	-10000	0	-10000	0	0
GNAI3	0.02	0.006	-10000	0	-10000	0	0
GNAI1	0.02	0.017	-10000	0	-0.33	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
S1PR3	0.021	0.015	0.32	1	-10000	0	1
S1PR2	0.02	0.005	-10000	0	-10000	0	0
EDG1	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.005	0.064	-10000	0	-0.45	2	2
MAPK3	-0.012	0.058	-10000	0	-0.59	1	1
MAPK1	-0.01	0.054	-10000	0	-0.57	1	1
JAK2	-0.022	0.078	0.2	2	-0.33	12	14
CXCR4	-0.013	0.06	-10000	0	-0.44	2	2
FLT1	0.02	0.008	-10000	0	-10000	0	0
RhoA/GDP	0.015	0.003	-10000	0	-10000	0	0
Rac1/GDP	0.014	0.005	-10000	0	-10000	0	0
SRC	-0.012	0.062	0.27	2	-0.44	2	4
S1P/S1P3/Gi	-0.005	0.064	-10000	0	-0.46	2	2
RAC1	0.019	0.007	-10000	0	-10000	0	0
RhoA/GTP	-0.001	0.069	-10000	0	-0.37	3	3
VEGFA	0.021	0.007	-10000	0	-10000	0	0
S1P/S1P2/Gi	-0.007	0.065	-10000	0	-0.29	6	6
VEGFR1 homodimer/VEGFA homodimer	0.029	0.013	-10000	0	-10000	0	0
RHOA	0.02	0.004	-10000	0	-10000	0	0
S1P/S1P3/Gq	0.007	0.037	-10000	0	-0.22	12	12
GNAQ	0.02	0.016	-10000	0	-0.33	1	1
GNAZ	-0.006	0.092	-10000	0	-0.33	39	39
G12/G13	0.027	0.011	-10000	0	-10000	0	0
GNA14	0.013	0.05	-10000	0	-0.33	11	11
GNA15	0.02	0.006	-10000	0	-10000	0	0
GNA12	0.019	0.007	-10000	0	-10000	0	0
GNA13	0.02	0.004	-10000	0	-10000	0	0
GNA11	0.019	0.016	-10000	0	-0.33	1	1
Rac1/GTP	-0.002	0.067	-10000	0	-0.38	3	3

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.017	0.034	-10000	0	-0.33	5	5
positive regulation of NF-kappaB transcription factor activity	0.023	0.027	-10000	0	-0.22	5	5
MAP2K4	0.005	0.026	-10000	0	-0.23	3	3
IKBKB	0.018	0.007	-10000	0	-10000	0	0
TNFRSF10B	0.018	0.008	-10000	0	-10000	0	0
TNFRSF10A	0.018	0.008	-10000	0	-10000	0	0
SMPD1	0.004	0.015	-10000	0	-0.14	5	5
IKBKG	0.02	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.017	0.017	-10000	0	-0.33	1	1
TRAIL/TRAILR2	0.023	0.027	-10000	0	-0.22	5	5
TRAIL/TRAILR3	0.021	0.039	-10000	0	-0.25	9	9
TRAIL/TRAILR1	0.023	0.027	-10000	0	-0.22	5	5
TRAIL/TRAILR4	0.023	0.028	-10000	0	-0.22	5	5
TRAIL/TRAILR1/DAP3/GTP	0.028	0.026	-10000	0	-0.17	4	4
IKK complex	0	0.046	-10000	0	-0.24	1	1
RIPK1	0.021	0.004	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.013	0.006	-10000	0	-10000	0	0
MAPK3	-0.017	0.025	0.27	1	-0.23	5	6
MAP3K1	0.013	0.023	-10000	0	-0.23	2	2
TRAILR4 (trimer)	0.017	0.017	-10000	0	-0.32	1	1
TRADD	0.02	0.004	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.018	0.008	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0	0.04	-10000	0	-0.19	8	8
CFLAR	0.021	0.002	-10000	0	-10000	0	0
MAPK1	-0.016	0.021	0.27	1	-0.23	3	4
TRAIL/TRAILR1/FADD/TRADD/RIP	0.046	0.034	-10000	0	-0.17	3	3
mol:ceramide	0.004	0.015	-10000	0	-0.14	5	5
FADD	0.02	0.004	-10000	0	-10000	0	0
MAPK8	-0.005	0.043	-10000	0	-0.26	4	4
TRAF2	0.021	0.004	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.014	0.038	-10000	0	-0.32	6	6
CHUK	0.021	0.003	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	0.032	0.028	-10000	0	-0.19	5	5
DAP3	0.018	0.008	-10000	0	-10000	0	0
CASP10	-0.003	0.041	0.16	26	-0.22	3	29
JNK cascade	0.023	0.027	-10000	0	-0.22	5	5
TRAIL (trimer)	0.017	0.034	-10000	0	-0.32	5	5
TNFRSF10C	0.014	0.038	-10000	0	-0.33	6	6
TRAIL/TRAILR1/DAP3/GTP/FADD	0.034	0.03	-10000	0	-0.16	4	4
TRAIL/TRAILR2/FADD	0.032	0.028	-10000	0	-0.19	5	5
cell death	0.004	0.016	0.14	1	-0.14	5	6
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.001	0.041	-10000	0	-0.19	8	8
TRAILR2 (trimer)	0.018	0.008	-10000	0	-10000	0	0
CASP8	0.009	0.05	-10000	0	-0.66	2	2
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.045	0.034	-10000	0	-0.17	3	3

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.021	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.018	0.062	0.22	4	-0.31	6	10
ERC1	0.02	0.005	-10000	0	-10000	0	0
RIP2/NOD2	0.027	0.012	-10000	0	-10000	0	0
NFKBIA	-0.015	0.021	0.2	4	-10000	0	4
BIRC2	0.02	0.005	-10000	0	-10000	0	0
IKBKB	0.018	0.007	-10000	0	-10000	0	0
RIPK2	0.019	0.007	-10000	0	-10000	0	0
IKBKG	0.002	0.05	-10000	0	-0.36	7	7
IKK complex/A20	0.028	0.076	-10000	0	-0.38	8	8
NEMO/A20/RIP2	0.019	0.007	-10000	0	-10000	0	0
XPO1	0.021	0.002	-10000	0	-10000	0	0
NEMO/ATM	0.023	0.075	-10000	0	-0.38	11	11
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.021	0.014	0.32	1	-10000	0	1
Exportin 1/RanGTP	0.028	0.01	0.21	1	-10000	0	1
IKK complex/ELKS	0.022	0.069	-10000	0	-0.36	10	10
BCL10/MALT1/TRAF6	0.037	0.016	-10000	0	-10000	0	0
NOD2	0.02	0.005	-10000	0	-10000	0	0
NFKB1	0.021	0.003	-10000	0	-10000	0	0
RELA	0.021	0.004	-10000	0	-10000	0	0
MALT1	0.019	0.007	-10000	0	-10000	0	0
cIAP1/UbcH5C	0.03	0.007	-10000	0	-10000	0	0
ATM	0.02	0.005	-10000	0	-10000	0	0
TNF/TNFR1A	0.022	0.044	0.23	1	-0.23	14	15
TRAF6	0.021	0.003	-10000	0	-10000	0	0
PRKCA	0.019	0.022	-10000	0	-0.33	2	2
CHUK	0.021	0.003	-10000	0	-10000	0	0
UBE2D3	0.021	0.003	-10000	0	-10000	0	0
TNF	0.011	0.06	0.32	1	-0.33	15	16
NF kappa B1 p50/RelA	0.042	0.013	-10000	0	-10000	0	0
BCL10	0.02	0.004	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.015	0.021	0.2	4	-10000	0	4
beta TrCP1/SCF ubiquitin ligase complex	0.02	0.005	-10000	0	-10000	0	0
TNFRSF1A	0.02	0.005	-10000	0	-10000	0	0
IKK complex	0.026	0.074	-10000	0	-0.38	10	10
CYLD	0.02	0.005	-10000	0	-10000	0	0
IKK complex/PKC alpha	0.031	0.073	-10000	0	-0.38	8	8

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	0.01	0.1	-10000	0	-0.37	15	15
CaM/Ca2+	0.015	0.003	-10000	0	-10000	0	0
AKT1	0.02	0.005	-10000	0	-10000	0	0
AKT2	0.02	0.005	-10000	0	-10000	0	0
STXBP4	0.021	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	-0.007	0.1	0.24	1	-0.38	19	20
YWHAZ	0.019	0.007	-10000	0	-10000	0	0
CALM1	0.02	0.005	-10000	0	-10000	0	0
YWHAQ	0.021	0.003	-10000	0	-10000	0	0
TBC1D4	-0.016	0.005	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.02	0.004	-10000	0	-10000	0	0
YWHAB	0.02	0.005	-10000	0	-10000	0	0
SNARE/Synip	0.038	0.014	-10000	0	-10000	0	0
YWHAG	0.02	0.004	-10000	0	-10000	0	0
ASIP	0.02	0.014	0.32	1	-10000	0	1
PRKCI	0.02	0.005	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0.015	0.003	-10000	0	-10000	0	0
RHOQ	0.021	0.003	-10000	0	-10000	0	0
GYS1	-0.005	0.002	-10000	0	-10000	0	0
PRKCZ	0.019	0.027	-10000	0	-0.33	3	3
TRIP10	0.02	0.005	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.027	0.008	-10000	0	-10000	0	0
AS160/14-3-3	0.004	0.051	-10000	0	-0.26	7	7
VAMP2	0.02	0.006	-10000	0	-10000	0	0
SLC2A4	-0.009	0.11	0.24	1	-0.42	19	20
STX4	0.021	0.003	-10000	0	-10000	0	0
GSK3B	0.01	0.004	-10000	0	-10000	0	0
SFN	0.025	0.043	0.32	9	-0.33	1	10
LNPEP	0.02	0.005	-10000	0	-10000	0	0
YWHAE	0.019	0.006	-10000	0	-10000	0	0

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.009	0.017	-10000	0	-0.23	2	2
CRKL	0.02	0.005	-10000	0	-10000	0	0
Rac1/GDP	0.014	0.005	-10000	0	-10000	0	0
DOCK1	0.021	0.003	-10000	0	-10000	0	0
ITGA4	0.02	0.022	-10000	0	-0.33	2	2
alpha4/beta7 Integrin/MAdCAM1	0.049	0.031	0.23	6	-0.18	3	9
EPO	0.021	0.027	0.32	4	-10000	0	4
alpha4/beta7 Integrin	0.029	0.021	-10000	0	-0.23	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.019	0.006	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.03	0.013	-10000	0	-0.23	1	1
EPO/EPOR (dimer)	0.029	0.02	0.23	4	-10000	0	4
lamellipodium assembly	0.003	0.05	-10000	0	-0.49	3	3
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
PI3K	0.029	0.014	-10000	0	-0.23	1	1
ARF6	0.02	0.004	-10000	0	-10000	0	0
JAK2	0.011	0.017	0.18	1	-0.29	1	2
PXN	0.021	0.003	-10000	0	-10000	0	0
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
MADCAM1	0.024	0.036	0.32	7	-10000	0	7
cell adhesion	0.047	0.031	0.22	6	-0.17	3	9
CRKL/CBL	0.028	0.01	-10000	0	-10000	0	0
ITGB1	0.021	0.004	-10000	0	-10000	0	0
SRC	-0.017	0.033	0.17	13	-0.18	2	15
ITGB7	0.02	0.016	-10000	0	-0.33	1	1
RAC1	0.019	0.007	-10000	0	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.039	0.023	0.22	1	-0.2	3	4
p130Cas/Crk/Dock1	-0.024	0.038	0.18	13	-10000	0	13
VCAM1	0.02	0.026	0.32	1	-0.33	2	3
RHOA	0.02	0.004	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.05	0.019	-10000	0	-0.18	1	1
BCAR1	-0.02	0.036	0.18	12	-0.17	3	15
EPOR	0.02	0.005	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.02	0.005	-10000	0	-10000	0	0
GIT1	0.021	0.004	-10000	0	-10000	0	0
Rac1/GTP	0.003	0.052	-10000	0	-0.51	3	3

Rapid glucocorticoid signaling

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
Gs family/GDP/Gbeta gamma	0.031	0.03	0.2	3	-0.16	8	11
MAPK9	0.004	0.001	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.008	0.013	0.16	3	-10000	0	3
GNB1/GNG2	0.026	0.015	-10000	0	-0.19	2	2
GNB1	0.021	0.004	-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	0.004	0.001	-10000	0	-10000	0	0
Gs family/GTP	0.011	0.025	0.18	3	-0.16	7	10
EntrezGene:2778	0	0	-10000	0	-10000	0	0
vasopressin secretion	0	0	-10000	0	-10000	0	0
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
glutamate secretion	0.002	0.005	0.048	7	-10000	0	7
GNAL	0.017	0.047	0.32	3	-0.33	7	10
GNG2	0.019	0.022	-10000	0	-0.33	2	2
CRH	0.019	0.024	0.32	3	-10000	0	3
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.004	0.001	-10000	0	-10000	0	0
MAPK11	0.003	0.016	-10000	0	-0.25	2	2

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.008	0.041	0.15	37	-0.16	2	39
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.015	0.036	0.12	29	-0.15	3	32
AP2	0.029	0.008	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.022	0.016	-10000	0	-10000	0	0
CLTB	0.02	0.005	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.008	0.006	-10000	0	-10000	0	0
CD4	0.014	0.046	-10000	0	-0.33	9	9
CLTA	0.02	0.006	-10000	0	-10000	0	0
mol:GTP	-0.002	0.002	-10000	0	-10000	0	0
ARFGAP1	-0.008	0.002	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.002	0.008	-10000	0	-10000	0	0
ARF1/GTP	0.022	0.014	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	-0.004	0.013	-10000	0	-10000	0	0
mol:Choline	-0.002	0.008	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.021	0.009	-10000	0	-10000	0	0
DDEF1	-0.001	0.008	-10000	0	-10000	0	0
ARF1/GDP	0.001	0.016	-10000	0	-0.09	8	8
AP2M1	0.02	0.005	-10000	0	-10000	0	0
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	-0.007	0.011	-10000	0	-10000	0	0
Rac/GTP	0.015	0.008	-10000	0	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.024	0.013	-10000	0	-10000	0	0
ARFIP2	0.01	0.02	-10000	0	-10000	0	0
COPA	0.019	0.007	-10000	0	-10000	0	0
RAC1	0.019	0.007	-10000	0	-10000	0	0
ARF1/GTP/coatomer protein complex	0	0.034	-10000	0	-0.17	13	13
ARF1/GTP/ARHGAP10	0.012	0.007	-10000	0	-10000	0	0
GGA3	0.02	0.004	-10000	0	-10000	0	0
ARF1/GTP/Membrin	0.012	0.025	-10000	0	-0.27	3	3
AP2A1	0.02	0.004	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.001	0.027	-10000	0	-0.16	11	11
ARF1/GDP/Membrin	0.016	0.029	-10000	0	-0.3	3	3
Arfaptin 2/Rac/GDP	0.02	0.018	-10000	0	-10000	0	0
CYTH2	0.024	0.008	-10000	0	-10000	0	0
ARF1/GTP/GGA3	0.026	0.012	-10000	0	-10000	0	0
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.014	0.005	-10000	0	-10000	0	0
mol:Brefeldin A	0	0	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.004	0.039	-10000	0	-0.2	13	13
PLD2	-0.002	0.008	-10000	0	-10000	0	0
ARF-GAP1/v-SNARE	-0.008	0.002	-10000	0	-10000	0	0
PIP5K1A	-0.002	0.008	-10000	0	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0.008	0.02	-10000	0	-0.13	3	3
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.002	0.008	-10000	0	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	-0.008	0.002	-10000	0	-10000	0	0
GOSR2	0.006	0.015	-10000	0	-0.31	1	1
USO1	0.004	0.029	-10000	0	-0.31	4	4
GBF1	0.004	0.029	-10000	0	-0.31	4	4
ARF1/GTP/Arfaptin 2	0.026	0.013	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.034	0.033	-10000	0	-0.19	9	9

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.019	0.007	-10000	0	-10000	0	0
SMAD2	0	0.043	0.25	2	-0.22	4	6
SMAD3	0.01	0.037	-10000	0	-10000	0	0
SMAD3/SMAD4	0.022	0.037	-10000	0	-0.4	2	2
SMAD4/Ubc9/PIASy	0.036	0.016	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.027	0.05	0.23	1	-0.21	3	4
PPM1A	0.021	0.004	-10000	0	-10000	0	0
CALM1	0.02	0.005	-10000	0	-10000	0	0
SMAD2/SMAD4	0.005	0.041	-10000	0	-0.21	7	7
MAP3K1	0.02	0.005	-10000	0	-10000	0	0
TRAP-1/SMAD4	0.027	0.019	-10000	0	-0.23	2	2
MAPK3	0.021	0.003	-10000	0	-10000	0	0
MAPK1	0.02	0.005	-10000	0	-10000	0	0
NUP214	0.021	0.004	-10000	0	-10000	0	0
CTDSP1	0.021	0.002	-10000	0	-10000	0	0
CTDSP2	0.02	0.005	-10000	0	-10000	0	0
CTDSPL	0.021	0.004	-10000	0	-10000	0	0
KPNB1	0.021	0.004	-10000	0	-10000	0	0
TGFBRAP1	0.02	0.022	-10000	0	-0.33	2	2
UBE2I	0.021	0.004	-10000	0	-10000	0	0
NUP153	0.021	0.003	-10000	0	-10000	0	0
KPNA2	0.023	0.03	0.32	5	-10000	0	5
PIAS4	0.02	0.005	-10000	0	-10000	0	0

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.021	0.004	-9999	-10000	0	0
ITGB7	0.02	0.016	-9999	-0.33	1	1
ITGA4	0.02	0.022	-9999	-0.33	2	2
alpha4/beta7 Integrin	0.029	0.021	-9999	-0.23	3	3
alpha4/beta1 Integrin	0.03	0.013	-9999	-0.23	1	1

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.02	0.005	-10000	0	-10000	0	0
Rac1/GDP	0.02	0.01	-10000	0	-10000	0	0
DOCK1	0.021	0.003	-10000	0	-10000	0	0
ITGA4	0.02	0.022	-10000	0	-0.33	2	2
RAC1	0.019	0.007	-10000	0	-10000	0	0
alpha4/beta7 Integrin	0.029	0.021	-10000	0	-0.23	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.019	0.006	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.039	0.016	-10000	0	-0.2	1	1
alpha4/beta7 Integrin/Paxillin	0.028	0.019	-10000	0	-0.18	3	3
lamellipodium assembly	-0.007	0.082	-10000	0	-0.38	17	17
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
PI3K	0.029	0.014	-10000	0	-0.23	1	1
ARF6	0.02	0.004	-10000	0	-10000	0	0
TLN1	0.019	0.016	-10000	0	-0.33	1	1
PXN	-0.016	0.004	-10000	0	-10000	0	0
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
ARF6/GTP	0.036	0.019	-10000	0	-0.16	1	1
cell adhesion	0.036	0.02	-10000	0	-0.16	2	2
CRKL/CBL	0.028	0.01	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.028	0.014	-10000	0	-0.18	1	1
ITGB1	0.021	0.004	-10000	0	-10000	0	0
ITGB7	0.02	0.016	-10000	0	-0.33	1	1
ARF6/GDP	0.022	0.009	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.037	0.024	0.22	1	-0.18	3	4
p130Cas/Crk/Dock1	0.037	0.018	-10000	0	-0.2	1	1
VCAM1	0.02	0.026	0.32	1	-0.33	2	3
alpha4/beta1 Integrin/Paxillin/Talin	0.037	0.02	-10000	0	-0.16	2	2
alpha4/beta1 Integrin/Paxillin/GIT1	0.038	0.018	-10000	0	-0.18	1	1
BCAR1	0.02	0.016	-10000	0	-0.33	1	1
mol:GDP	-0.037	0.018	0.17	1	-10000	0	1
CBL	0.02	0.005	-10000	0	-10000	0	0
PRKACA	0.02	0.005	-10000	0	-10000	0	0
GIT1	0.021	0.004	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.037	0.02	-10000	0	-0.16	2	2
Rac1/GTP	-0.008	0.09	-10000	0	-0.42	17	17

Atypical NF-kappaB 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.029	0.014	-10000	0	-0.23	1	1
FBXW11	0.02	0.005	-10000	0	-10000	0	0
NF kappa B1 p50/c-Rel	-0.017	0.007	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.02	0.045	0.22	6	-0.18	2	8
NFKBIA	0.002	0.011	-10000	0	-0.17	2	2
MAPK14	0.021	0.004	-10000	0	-10000	0	0
NF kappa B1 p105/p50	-0.016	0.008	-10000	0	-10000	0	0
ARRB2	0.007	0.002	-10000	0	-10000	0	0
REL	0.021	0.002	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	-0.016	0.008	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	-0.017	0.007	-10000	0	-10000	0	0
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
NF kappa B1 p50 dimer	-0.014	0.013	0.24	1	-10000	0	1
PIK3R1	0.02	0.016	-10000	0	-0.33	1	1
NFKB1	-0.014	0.006	-10000	0	-10000	0	0
RELA	0.021	0.004	-10000	0	-10000	0	0
positive regulation of anti-apoptosis	0.008	0.035	-10000	0	-0.19	5	5
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.018	0.04	-10000	0	-0.19	1	1
SRC	0.02	0.004	-10000	0	-10000	0	0
PI3K	0.029	0.014	-10000	0	-0.23	1	1
NF kappa B1 p50/RelA	0.008	0.034	-10000	0	-0.18	4	4
IKBKB	0.018	0.007	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.02	0.005	-10000	0	-10000	0	0
SYK	0.019	0.022	-10000	0	-0.33	2	2
I kappa B alpha/PIK3R1	0.026	0.053	0.24	12	-0.18	2	14
cell death	0.017	0.039	-10000	0	-0.18	1	1
NF kappa B1 p105/c-Rel	-0.017	0.007	-10000	0	-10000	0	0
LCK	0.02	0.026	0.32	1	-0.33	2	3
BCL3	0.02	0.016	-10000	0	-0.33	1	1

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.039	0.019	-9999	-0.18	2	2
E-cadherin/beta catenin	0.029	0.017	-9999	-0.22	2	2
CTNNB1	0.021	0.004	-9999	-10000	0	0
JUP	0.021	0.004	-9999	-10000	0	0
CDH1	0.019	0.022	-9999	-0.33	2	2

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.021	0.002	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.019	0.008	-10000	0	-10000	0	0
MDM2/SUMO1	0.026	0.031	-10000	0	-0.21	3	3
HDAC4	0.021	0.003	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	-0.019	0.009	-10000	0	-10000	0	0
SUMO1	0.021	0.003	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1	0.005	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
XPO1	-0.005	0.016	-10000	0	-0.16	1	1
EntrezGene:23636	0	0	-10000	0	-10000	0	0
RAN	0.021	0.014	0.32	1	-10000	0	1
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.021	0.002	-10000	0	-10000	0	0
SUMO1/HDAC4	0.027	0.03	-10000	0	-0.2	3	3
SUMO1/HDAC1	0.027	0.031	-10000	0	-0.21	3	3
RANGAP1	0.02	0.004	-10000	0	-10000	0	0
MDM2/SUMO1/SUMO1	0.045	0.023	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.006	0.002	-10000	0	-10000	0	0
Ran/GTP	0.017	0.029	-10000	0	-0.19	4	4
EntrezGene:23225	0	0	-10000	0	-10000	0	0
MDM2	0.02	0.005	-10000	0	-10000	0	0
UBE2I	0.021	0.004	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.013	0.033	0.21	4	-0.19	4	8
NPC	0.013	0.001	-10000	0	-10000	0	0
PIAS2	0.019	0.006	-10000	0	-10000	0	0
PIAS1	0.021	0.004	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
IKK alpha homodimer	0.03	0.006	-9999	-9999
FBXW11	0.02	0.005	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-9999
beta TrCP1/SCF ubiquitin ligase complex	0.02	0.005	-9999	-9999
CHUK	0.021	0.003	-9999	-9999
NF kappa B2 p100/RelB	0.056	0.021	-9999	-9999
NFKB1	0.021	0.003	-9999	-9999
MAP3K14	0.021	0.003	-9999	-9999
NF kappa B1 p50/RelB	0.03	0.007	-9999	-9999
RELB	0.02	0.004	-9999	-9999
NFKB2	0.021	0.003	-9999	-9999
NF kappa B2 p52/RelB	0.027	0.007	-9999	-9999
regulation of B cell activation	0.027	0.007	-9999	-9999

pid_entity	TCGA.S2.AA1A	TCGA.O1.A52J	TCGA.NJ.A7XG	TCGA.NJ.A55R
109_MAP3K5	0.0088	-0.02	-0.13	0.0088
47_PPARGC1A	0.021	0.021	-0.33	0.021
105_BMP4	0.021	0.021	0.021	0.021
105_BMP6	0.021	-0.33	-0.33	0.021
105_BMP7	0.32	0	0.021	0.021
105_BMP2	0.021	0.021	0.021	0.021
131_RELN/VLDLR	0.055	-0.18	-0.16	0.055
30_TGFB1/TGF beta receptor Type II	0.021	0.021	0.021	-0.024
84_STAT5B	0.015	0.074	-0.19	0.016
84_STAT5A	0.015	0.074	-0.19	0.016