PARADIGM pathway analysis of mRNA expression data - Ovarian Serous Cystadenocarcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
FOXM1 transcription factor network	418
PLK1 signaling events	235
TCGA08_retinoblastoma	234
PLK2 and PLK4 events	215
Aurora B signaling	186
Circadian rhythm pathway	149
Signaling events regulated by Ret tyrosine kinase	128
TCGA08_p53	123
Osteopontin-mediated events	118
Nongenotropic Androgen signaling	106

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	0.7346	418	21333	51	-0.035	2.3	1000	-1000	-0.16	-1000
PLK1 signaling events	0.4130	235	19994	85	-0.13	0.32	1000	-1000	-0.028	-1000
TCGA08_retinoblastoma	0.4112	234	1878	8	-0.11	0.14	1000	-1000	-0.008	-1000
PLK2 and PLK4 events	0.3779	215	646	3	0.029	0.12	1000	-1000	-0.011	-1000
Aurora B signaling	0.3269	186	12472	67	-0.25	0.42	1000	-1000	-0.028	-1000
Circadian rhythm pathway	0.2619	149	3295	22	-0.079	0.32	1000	-1000	-0.034	-1000
Signaling events regulated by Ret tyrosine kinase	0.2250	128	10516	82	-0.24	0.066	1000	-1000	-0.046	-1000
TCGA08_p53	0.2162	123	866	7	-0.075	0.003	1000	-1000	-0.009	-1000
Osteopontin-mediated events	0.2074	118	4506	38	-0.13	0.17	1000	-1000	-0.038	-1000
Nongenotropic Androgen signaling	0.1863	106	5552	52	-0.2	0.094	1000	-1000	-0.022	-1000
BARD1 signaling events	0.1845	105	5989	57	-0.051	0.22	1000	-1000	-0.03	-1000
HIF-1-alpha transcription factor network	0.1757	100	7642	76	-0.027	0.32	1000	-1000	-0.056	-1000
IL2 signaling events mediated by STAT5	0.1757	100	2210	22	-0.42	0.21	1000	-1000	-0.026	-1000
mTOR signaling pathway	0.1599	91	4837	53	-0.18	0.047	1000	-1000	-0.038	-1000
Insulin Pathway	0.1599	91	6771	74	-0.2	0.047	1000	-1000	-0.034	-1000
S1P3 pathway	0.1599	91	3857	42	-0.56	0.02	1000	-1000	-0.03	-1000
Aurora A signaling	0.1547	88	5325	60	-0.25	0.29	1000	-1000	-0.02	-1000
IGF1 pathway	0.1511	86	4958	57	-0.1	0.085	1000	-1000	-0.04	-1000
Endothelins	0.1371	78	7571	96	-0.11	0.15	1000	-1000	-0.034	-1000
TCGA08_rtk_signaling	0.1371	78	2042	26	-0.18	0.12	1000	-1000	-0.013	-1000
Coregulation of Androgen receptor activity	0.1248	71	5446	76	-0.34	0.13	1000	-1000	-0.023	-1000
Signaling events mediated by PRL	0.1248	71	2441	34	-0.083	0.16	1000	-1000	-0.019	-1000
PDGFR-alpha signaling pathway	0.1213	69	3059	44	-0.084	0.047	1000	-1000	-0.013	-1000
Syndecan-1-mediated signaling events	0.1195	68	2330	34	-0.1	0.047	1000	-1000	-0.019	-1000
Integrins in angiogenesis	0.1178	67	5643	84	-0.2	0.079	1000	-1000	-0.037	-1000
LPA receptor mediated events	0.1178	67	6880	102	-0.075	0.035	1000	-1000	-0.036	-1000
Ephrin B reverse signaling	0.1125	64	3108	48	-0.16	0.047	1000	-1000	-0.028	-1000
IL1-mediated signaling events	0.1107	63	3956	62	-0.12	0.1	1000	-1000	-0.037	-1000
Reelin signaling pathway	0.1054	60	3364	56	-0.075	0.047	1000	-1000	-0.034	-1000
Ras signaling in the CD4+ TCR pathway	0.1037	59	1004	17	-0.007	0.12	1000	-1000	-0.011	-1000
Thromboxane A2 receptor signaling	0.0984	56	5973	105	-0.2	0.064	1000	-1000	-0.043	-1000
IL4-mediated signaling events	0.0967	55	5094	91	-0.65	0.22	1000	-1000	-0.16	-1000
Nectin adhesion pathway	0.0967	55	3521	63	-0.12	0.047	1000	-1000	-0.036	-1000
FAS signaling pathway (CD95)	0.0896	51	2401	47	-0.057	0.065	1000	-1000	-0.032	-1000
Plasma membrane estrogen receptor signaling	0.0879	50	4359	86	-0.096	0.12	1000	-1000	-0.042	-1000
Signaling events mediated by the Hedgehog family	0.0861	49	2569	52	-0.075	0.12	1000	-1000	-0.025	-1000
amb2 Integrin signaling	0.0861	49	4020	82	-0.14	0.075	1000	-1000	-0.032	-1000
IL23-mediated signaling events	0.0861	49	2940	60	-0.076	0.2	1000	-1000	-0.12	-1000
p75(NTR)-mediated signaling	0.0808	46	5826	125	-0.18	0.1	1000	-1000	-0.034	-1000
Effects of Botulinum toxin	0.0808	46	1216	26	-0.15	0.011	1000	-1000	-0.022	-1000
TRAIL signaling pathway	0.0791	45	2184	48	-0.12	0.015	1000	-1000	-0.028	-1000
Signaling mediated by p38-gamma and p38-delta	0.0773	44	674	15	-0.092	0.04	1000	-1000	-0.013	-1000
HIF-2-alpha transcription factor network	0.0721	41	1764	43	-0.14	0.18	1000	-1000	-0.047	-1000
Retinoic acid receptors-mediated signaling	0.0721	41	2402	58	-0.38	0.23	1000	-1000	-0.039	-1000
Syndecan-4-mediated signaling events	0.0721	41	2777	67	-0.045	0.089	1000	-1000	-0.031	-1000
Syndecan-2-mediated signaling events	0.0703	40	2771	69	-0.054	0.075	1000	-1000	-0.017	-1000
FoxO family signaling	0.0703	40	2595	64	-0.072	0.3	1000	-1000	-0.027	-1000
Cellular roles of Anthrax toxin	0.0685	39	1551	39	-0.14	0.014	1000	-1000	-0.011	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0685	39	2062	52	-0.16	0.044	1000	-1000	-0.024	-1000
IL2 signaling events mediated by PI3K	0.0668	38	2221	58	-0.17	0.045	1000	-1000	-0.055	-1000
Insulin-mediated glucose transport	0.0650	37	1201	32	-0.23	0.1	1000	-1000	-0.026	-1000
Aurora C signaling	0.0615	35	248	7	-0.006	0.046	1000	-1000	-0.013	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0615	35	1310	37	-0.075	0.047	1000	-1000	-0.023	-1000
Fc-epsilon receptor I signaling in mast cells	0.0598	34	3392	97	-0.074	0.047	1000	-1000	-0.039	-1000
Paxillin-dependent events mediated by a4b1	0.0598	34	1248	36	-0.075	0.047	1000	-1000	-0.029	-1000
Signaling events mediated by PTP1B	0.0580	33	2534	76	-0.2	0.082	1000	-1000	-0.033	-1000
Canonical NF-kappaB pathway	0.0562	32	1285	39	-0.022	0.073	1000	-1000	-0.035	-1000
Regulation of Telomerase	0.0562	32	3281	102	-0.27	0.084	1000	-1000	-0.062	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0562	32	1078	33	-0.051	0.13	1000	-1000	-0.021	-1000
Regulation of Androgen receptor activity	0.0562	32	2300	70	-0.42	0.021	1000	-1000	-0.042	-1000
Caspase cascade in apoptosis	0.0545	31	2331	74	-0.047	0.077	1000	-1000	-0.024	-1000
IL6-mediated signaling events	0.0545	31	2364	75	-0.28	0.11	1000	-1000	-0.035	-1000
EPHB forward signaling	0.0510	29	2531	85	-0.075	0.12	1000	-1000	-0.04	-1000
Class I PI3K signaling events	0.0510	29	2177	73	-0.047	0.12	1000	-1000	-0.027	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0510	29	3510	120	-0.16	0.12	1000	-1000	-0.036	-1000
LPA4-mediated signaling events	0.0492	28	346	12	-0.085	0	1000	-1000	-0.012	-1000
ErbB4 signaling events	0.0492	28	1984	69	-0.23	0.21	1000	-1000	-0.043	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0492	28	2436	85	-0.075	0.047	1000	-1000	-0.031	-1000
BMP receptor signaling	0.0475	27	2244	81	-0.14	0.041	1000	-1000	-0.046	-1000
E-cadherin signaling in keratinocytes	0.0475	27	1176	43	-0.073	0.044	1000	-1000	-0.023	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0457	26	610	23	-0.013	0.21	1000	-1000	-0.018	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0457	26	1420	54	-0.048	0.021	1000	-1000	-0.042	-1000
Glypican 1 network	0.0457	26	1277	48	-0.13	0.036	1000	-1000	-0.022	-1000
IL12-mediated signaling events	0.0439	25	2241	87	-0.39	0.13	1000	-1000	-0.11	-1000
Glucocorticoid receptor regulatory network	0.0439	25	2921	114	-0.29	0.14	1000	-1000	-0.046	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0439	25	2121	83	-0.15	0.21	1000	-1000	-0.027	-1000
Canonical Wnt signaling pathway	0.0439	25	1305	51	-0.34	0.13	1000	-1000	-0.038	-1000
PDGFR-beta signaling pathway	0.0439	25	2507	97	-0.088	0.13	1000	-1000	-0.033	-1000
ErbB2/ErbB3 signaling events	0.0422	24	1596	65	-0.019	0.13	1000	-1000	-0.033	-1000
EGFR-dependent Endothelin signaling events	0.0404	23	486	21	-0.03	0.007	1000	-1000	-0.03	-1000
Regulation of nuclear SMAD2/3 signaling	0.0387	22	3065	136	-0.18	0.14	1000	-1000	-0.026	-1000
Wnt signaling	0.0387	22	157	7	-0.006	0.021	1000	-1000	-0.011	-1000
Arf6 signaling events	0.0369	21	1337	62	-0.046	0.029	1000	-1000	-0.018	-1000
IFN-gamma pathway	0.0369	21	1490	68	-0.075	0.077	1000	-1000	-0.043	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0369	21	1579	74	-0.12	0.029	1000	-1000	-0.04	-1000
a4b1 and a4b7 Integrin signaling	0.0351	20	103	5	-0.006	0.007	1000	-1000	-0.009	-1000
Presenilin action in Notch and Wnt signaling	0.0351	20	1236	61	-0.32	0.025	1000	-1000	-0.033	-1000
TCR signaling in naïve CD8+ T cells	0.0351	20	1938	93	-0.049	0.12	1000	-1000	-0.039	-1000
Atypical NF-kappaB pathway	0.0334	19	601	31	-0.075	0.047	1000	-1000	-0.014	-1000
Ceramide signaling pathway	0.0316	18	1409	76	-0.055	0.048	1000	-1000	-0.028	-1000
Syndecan-3-mediated signaling events	0.0316	18	641	35	-0.047	0.019	1000	-1000	-0.019	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0316	18	818	45	-0.07	0.024	1000	-1000	-0.04	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0316	18	1452	78	-0.16	0.047	1000	-1000	-0.068	-1000
IL27-mediated signaling events	0.0299	17	917	51	-0.054	0.13	1000	-1000	-0.031	-1000
E-cadherin signaling in the nascent adherens junction	0.0299	17	1325	76	-0.075	0.047	1000	-1000	-0.045	-1000
Ephrin A reverse signaling	0.0281	16	112	7	-0.028	0.006	1000	-1000	-0.008	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0281	16	2076	125	-0.08	0.047	1000	-1000	-0.051	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0281	16	1129	68	-0.12	0.008	1000	-1000	-0.061	-1000
FOXA2 and FOXA3 transcription factor networks	0.0264	15	714	46	-0.019	0.21	1000	-1000	-0.071	-1000
Regulation of p38-alpha and p38-beta	0.0264	15	858	54	-0.094	0.03	1000	-1000	-0.036	-1000
Arf6 downstream pathway	0.0246	14	629	43	-0.021	0.019	1000	-1000	-0.017	-1000
ceramide signaling pathway	0.0246	14	706	49	-0.055	0.001	1000	-1000	-0.031	-1000
Signaling mediated by p38-alpha and p38-beta	0.0246	14	618	44	-0.088	0.02	1000	-1000	-0.021	-1000
Calcium signaling in the CD4+ TCR pathway	0.0246	14	452	31	-0.077	0	1000	-1000	-0.031	-1000
BCR signaling pathway	0.0246	14	1478	99	-0.075	0.047	1000	-1000	-0.042	-1000
Noncanonical Wnt signaling pathway	0.0228	13	358	26	-0.018	0.024	1000	-1000	-0.024	-1000
S1P1 pathway	0.0228	13	473	36	-0.009	0.037	1000	-1000	-0.039	-1000
E-cadherin signaling events	0.0228	13	69	5	-0.013	0.001	1000	-1000	-0.011	-1000
Arf1 pathway	0.0228	13	731	54	-0.024	0.005	1000	-1000	-0.013	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0211	12	430	34	-0.017	0.021	1000	-1000	-0.014	-1000
Signaling events mediated by HDAC Class I	0.0211	12	1270	104	-0.021	0.026	1000	-1000	-0.028	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0176	10	290	28	-0.034	0.036	1000	-1000	-0.014	-1000
EPO signaling pathway	0.0176	10	576	55	-0.085	0.029	1000	-1000	-0.038	-1000
Signaling events mediated by HDAC Class III	0.0176	10	411	40	-0.047	0.01	1000	-1000	-0.01	-1000
VEGFR1 specific signals	0.0176	10	609	56	-0.075	0.047	1000	-1000	-0.035	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0158	9	794	88	-0.075	0.075	1000	-1000	-0.074	-1000
S1P5 pathway	0.0141	8	152	17	-0.009	0.036	1000	-1000	-0.011	-1000
Signaling events mediated by HDAC Class II	0.0123	7	564	75	-0.046	0.014	1000	-1000	-0.017	-1000
JNK signaling in the CD4+ TCR pathway	0.0123	7	124	17	-0.015	0.008	1000	-1000	-0.015	-1000
Hedgehog signaling events mediated by Gli proteins	0.0123	7	507	65	-0.056	0.035	1000	-1000	-0.028	-1000
Class I PI3K signaling events mediated by Akt	0.0123	7	534	68	-0.14	0.036	1000	-1000	-0.027	-1000
S1P4 pathway	0.0123	7	182	25	-0.008	0.036	1000	-1000	-0.012	-1000
p38 MAPK signaling pathway	0.0123	7	325	44	-0.012	0.02	1000	-1000	-0.036	-1000
Class IB PI3K non-lipid kinase events	0.0105	6	18	3	-0.003	-1000	1000	-1000	-0.005	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0088	5	146	27	-0.008	0.014	1000	-1000	-0.022	-1000
Arf6 trafficking events	0.0088	5	389	71	-0.008	0.009	1000	-1000	-0.028	-1000
Alternative NF-kappaB pathway	0.0070	4	60	13	-0.01	0.016	1000	-1000	-0.011	-1000
Visual signal transduction: Rods	0.0035	2	149	52	-0.017	0.012	1000	-1000	-0.032	-1000
Visual signal transduction: Cones	0.0000	0	30	38	-0.011	0.011	1000	-1000	-0.012	-1000
Glypican 2 network	0.0000	0	3	4	-0.007	-1000	1000	-1000	-0.01	-1000
Rapid glucocorticoid signaling	0.0000	0	17	20	-0.006	0.006	1000	-1000	-0.009	-1000
Total	NA	5903	319922	7203	-15	-2000	131000	-131000	-4.2	-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	1.3	0.29	1.3	527	-10000	0	527
PLK1	0.47	0.28	0.65	320	-10000	0	320
BIRC5	0.49	0.3	0.74	262	-10000	0	262
HSPA1B	1.3	0.29	1.3	538	-10000	0	538
MAP2K1	0.45	0.13	0.47	543	-10000	0	543
BRCA2	1.4	0.41	1.5	528	-10000	0	528
FOXM1	2.3	0.81	2.4	537	-10000	0	537
XRCC1	1.3	0.29	1.3	527	-10000	0	527
FOXM1B/p19	0.73	0.59	1.2	335	-10000	0	335
Cyclin D1/CDK4	0.71	0.48	1	382	-10000	0	382
CDC2	1.9	0.52	2	540	-10000	0	540
TGFA	0.76	0.5	1.1	382	-10000	0	382
SKP2	1.4	0.4	1.5	525	-10000	0	525
CCNE1	0.27	0.068	0.3	515	-10000	0	515
CKS1B	1.5	0.44	1.6	527	-10000	0	527
RB1	0	0.03	0.62	1	-10000	0	1
FOXM1C/SP1	0.93	0.39	1.1	463	-10000	0	463
AURKB	0.5	0.31	0.7	312	-10000	0	312
CENPF	1.7	0.41	1.8	533	-10000	0	533
CDK4	0.11	0.066	0.17	193	-10000	0	193
MYC	0.92	0.38	1.1	469	-10000	0	469
CHEK2	0.51	0.16	0.53	544	-10000	0	544
ONECUT1	0.8	0.53	1.2	384	-10000	0	384
CDKN2A	0.049	0.16	0.24	183	-0.29	61	244
LAMA4	1.2	0.48	1.3	484	-0.97	2	486
FOXM1B/HNF6	0.81	0.54	1.2	380	-10000	0	380
FOS	1.1	0.51	1.4	467	-10000	0	467
SP1	-0.035	0.082	-10000	0	-0.28	58	58
CDC25B	1.3	0.29	1.3	525	-10000	0	525
response to radiation	0.23	0.059	0.24	532	-10000	0	532
CENPB	1.3	0.29	1.3	524	-10000	0	524
CENPA	1.3	0.3	1.4	527	-10000	0	527
NEK2	1.6	0.44	1.7	527	-10000	0	527
HIST1H2BA	1.3	0.29	1.3	527	-10000	0	527
CCNA2	0.27	0.082	0.3	495	-10000	0	495
EP300	-0.007	0.018	-10000	0	-0.31	2	2
CCNB1/CDK1	1.8	0.47	1.8	535	-10000	0	535
CCNB2	1.7	0.4	1.8	539	-10000	0	539
CCNB1	1.9	0.54	2	539	-10000	0	539
ETV5	1.3	0.34	1.4	530	-10000	0	530
ESR1	1.1	0.52	1.3	455	-1	2	457
CCND1	0.8	0.53	1.2	384	-10000	0	384
GSK3A	0.24	0.061	0.25	513	-10000	0	513
Cyclin A-E1/CDK1-2	0.51	0.13	0.52	551	-10000	0	551
CDK2	0.18	0.1	0.3	235	-10000	0	235
G2/M transition of mitotic cell cycle	0.44	0.13	0.46	543	-10000	0	543
FOXM1B/Cbp/p300	-0.003	0.036	-10000	0	-10000	0	0
GAS1	1.1	0.53	1.3	454	-0.98	1	455
MMP2	1.1	0.54	1.4	467	-0.97	4	471
RB1/FOXM1C	0.78	0.52	1.1	389	-10000	0	389
CREBBP	-0.012	0.042	-10000	0	-0.31	11	11

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.13	0.048	-10000	0	-0.15	494	494
BUB1B	0.22	0.068	0.24	514	-10000	0	514
PLK1	0.1	0.037	0.11	518	-10000	0	518
PLK1S1	0.051	0.021	0.058	456	-10000	0	456
KIF2A	0.088	0.032	0.099	447	-0.12	1	448
regulation of mitotic centrosome separation	0.1	0.036	0.11	518	-10000	0	518
GOLGA2	-0.006	0	-10000	0	-10000	0	0
Hec1/SPC24	0.25	0.1	0.28	508	-10000	0	508
WEE1	0.15	0.042	0.17	444	-10000	0	444
cytokinesis	0.25	0.089	0.28	499	-10000	0	499
PP2A-alpha B56	0.027	0.058	-10000	0	-10000	0	0
AURKA	0.14	0.036	0.14	538	-10000	0	538
PICH/PLK1	0.27	0.091	0.28	543	-10000	0	543
CENPE	0.1	0.056	0.15	224	-10000	0	224
RhoA/GTP	-0.004	0.012	-10000	0	-0.21	2	2
positive regulation of microtubule depolymerization	0.087	0.032	0.099	447	-0.12	1	448
PPP2CA	-0.006	0.013	-10000	0	-0.31	1	1
FZR1	-0.006	0	-10000	0	-10000	0	0
TPX2	0.16	0.03	0.16	556	-10000	0	556
PAK1	0.012	0.041	0.24	18	-10000	0	18
SPC24	0.063	0.11	0.24	157	-10000	0	157
FBXW11	-0.006	0	-10000	0	-10000	0	0
CLSPN	0.07	0.041	0.15	83	-10000	0	83
GORASP1	-0.006	0	-10000	0	-10000	0	0
metaphase	0.001	0.002	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.051	0.021	0.058	456	-10000	0	456
G2 phase of mitotic cell cycle	0.007	0.002	0.009	121	-10000	0	121
STAG2	0.001	0.043	0.24	16	-0.31	1	17
GRASP65/GM130/RAB1/GTP	0	0.001	-10000	0	-10000	0	0
spindle elongation	0.1	0.036	0.11	518	-10000	0	518
ODF2	0.011	0.003	-10000	0	-10000	0	0
BUB1	0.029	0.07	0.39	2	-10000	0	2
TPT1	0.051	0.023	0.094	43	-0.18	1	44
CDC25C	0.12	0.075	0.2	259	-10000	0	259
CDC25B	0.028	0.028	0.26	8	-10000	0	8
SGOL1	0.13	0.048	0.15	494	-10000	0	494
RHOA	-0.007	0.018	-10000	0	-0.31	2	2
CCNB1/CDK1	0.27	0.083	0.28	531	-10000	0	531
CDC14B	0.004	0.002	-10000	0	-10000	0	0
CDC20	0.18	0.1	0.24	438	-10000	0	438
PLK1/PBIP1	0.01	0.043	0.21	24	-10000	0	24
mitosis	0	0.001	-10000	0	-10000	0	0
FBXO5	0.17	0.075	0.2	479	-10000	0	479
CDC2	0.24	0.045	0.24	549	-10000	0	549
NDC80	0.21	0.078	0.24	505	-10000	0	505
metaphase plate congression	0.065	0.023	0.11	41	-0.15	1	42
ERCC6L	0.27	0.089	0.28	536	-10000	0	536
NLP/gamma Tubulin	0.052	0.023	0.077	212	-10000	0	212
microtubule cytoskeleton organization	0.051	0.023	0.094	43	-0.17	1	44
G2/M transition DNA damage checkpoint	0.001	0.001	-10000	0	-10000	0	0
PPP1R12A	0.006	0.003	-10000	0	-10000	0	0
interphase	0.001	0.001	-10000	0	-10000	0	0
PLK1/PRC1-2	0.32	0.12	0.35	509	-10000	0	509
GRASP65/GM130/RAB1/GTP/PLK1	0.039	0.031	0.2	1	-10000	0	1
RAB1A	-0.005	0.01	0.24	1	-10000	0	1
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.12	0.068	0.13	516	-10000	0	516
mitotic prometaphase	0.003	0.002	0.033	1	-10000	0	1
proteasomal ubiquitin-dependent protein catabolic process	0.099	0.042	-10000	0	-10000	0	0
microtubule-based process	0.22	0.077	0.24	503	-10000	0	503
Golgi organization	0.1	0.036	0.11	518	-10000	0	518
Cohesin/SA2	0.054	0.046	0.085	300	-10000	0	300
PPP1CB/MYPT1	0.012	0.01	-10000	0	-0.22	1	1
KIF20A	0.2	0.091	0.24	477	-10000	0	477
APC/C/CDC20	0.21	0.086	0.25	447	-10000	0	447
PPP2R1A	-0.006	0	-10000	0	-10000	0	0
chromosome segregation	0.01	0.042	0.21	24	-10000	0	24
PRC1	0.18	0.11	0.24	429	-10000	0	429
ECT2	0.22	0.06	0.24	536	-10000	0	536
C13orf34	0.11	0.068	0.13	447	-10000	0	447
NUDC	0.065	0.023	0.11	41	-0.15	1	42
regulation of attachment of spindle microtubules to kinetochore	0.22	0.068	0.24	514	-10000	0	514
spindle assembly	0.076	0.03	0.087	448	-10000	0	448
spindle stabilization	0.051	0.021	0.058	456	-10000	0	456
APC/C/HCDH1	0.006	0.003	-10000	0	-10000	0	0
MKLP2/PLK1	0.22	0.078	0.24	503	-10000	0	503
CCNB1	0.2	0.095	0.25	448	-10000	0	448
PPP1CB	0.006	0.014	-10000	0	-0.31	1	1
BTRC	-0.006	0	-10000	0	-10000	0	0
ROCK2	0.071	0.028	0.16	11	-10000	0	11
TUBG1	0.052	0.023	0.1	43	-10000	0	43
G2/M transition of mitotic cell cycle	0.26	0.072	0.27	542	-10000	0	542
MLF1IP	0.007	0.042	0.21	24	-10000	0	24
INCENP	0.01	0.014	0.24	2	-10000	0	2

×

TCGA08_retinoblastoma

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
CDKN2B	-0.032	0.016	-10000	0	-10000	0	0
CDKN2C	-0.002	0.059	0.24	28	-10000	0	28
CDKN2A	0.14	0.12	0.25	314	-10000	0	314
CCND2	-0.095	0.098	-10000	0	-0.18	304	304
RB1	0.098	0.095	0.18	307	-10000	0	307
CDK4	-0.092	0.093	-10000	0	-0.17	307	307
CDK6	-0.096	0.098	-10000	0	-0.18	310	310
G1/S progression	-0.11	0.082	-10000	0	-0.18	308	308

×

PLK2 and PLK4 events

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
PLK2	0.029	0.094	0.24	86	-0.31	5	91
PLK4	0.1	0.12	0.24	251	-10000	0	251
regulation of centriole replication	0.12	0.13	0.23	301	-0.21	3	304

×

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	0.39	0.16	0.42	527	-10000	0	527
STMN1	0.11	0.16	0.29	209	-10000	0	209
Aurora B/RasGAP/Survivin	0.073	0.091	0.21	150	-0.16	1	151
Chromosomal passenger complex/Cul3 protein complex	0.015	0.11	0.22	77	-10000	0	77
BIRC5	0.067	0.093	0.25	115	-10000	0	115
DES	-0.061	0.15	-10000	0	-0.42	82	82
Aurora C/Aurora B/INCENP	0.054	0.057	0.16	120	-10000	0	120
Aurora B/TACC1	-0.1	0.093	0.15	15	-0.17	356	371
Aurora B/PP2A	0.045	0.063	0.17	119	-10000	0	119
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	0.018	0.038	0.17	8	-0.13	6	14
mitotic metaphase/anaphase transition	-0.008	0.005	-10000	0	-10000	0	0
NDC80	0.24	0.13	0.27	506	-10000	0	506
Cul3 protein complex	-0.05	0.09	0.16	7	-0.18	185	192
KIF2C	0.23	0.088	0.25	503	-10000	0	503
PEBP1	0.016	0.004	-10000	0	-10000	0	0
KIF20A	0.2	0.088	0.24	477	-10000	0	477
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.044	0.065	0.17	118	-0.2	2	120
SEPT1	-0.006	0	-10000	0	-10000	0	0
SMC2	0.097	0.12	0.24	236	-10000	0	236
SMC4	0.23	0.053	0.24	542	-10000	0	542
NSUN2/NPM1/Nucleolin	0.059	0.11	0.28	111	-10000	0	111
PSMA3	-0.005	0.024	0.24	4	-0.31	1	5
G2/M transition of mitotic cell cycle	-0.001	0.003	-10000	0	-10000	0	0
H3F3B	0.034	0.067	0.16	118	-0.23	6	124
AURKB	0.061	0.093	0.24	119	-10000	0	119
AURKC	-0.006	0	-10000	0	-10000	0	0
CDCA8	0.055	0.082	0.25	84	-10000	0	84
cytokinesis	0.014	0.071	0.34	23	-10000	0	23
Aurora B/Septin1	0.069	0.14	0.39	91	-10000	0	91
AURKA	0.23	0.055	0.24	538	-10000	0	538
INCENP	0.023	0.015	0.25	2	-10000	0	2
KLHL13	-0.1	0.15	0.24	7	-0.31	183	190
BUB1	0.22	0.062	0.24	526	-10000	0	526
hSgo1/Aurora B/Survivin	0.15	0.098	0.2	420	-10000	0	420
EVI5	0.011	0.016	0.24	1	-0.28	1	2
RhoA/GTP	0.24	0.17	0.34	400	-10000	0	400
SGOL1	0.21	0.084	0.24	494	-10000	0	494
CENPA	0.21	0.092	0.23	526	-10000	0	526
NCAPG	0.22	0.063	0.24	530	-10000	0	530
Aurora B/HC8 Proteasome	0.046	0.065	0.17	123	-0.21	1	124
NCAPD2	0.12	0.12	0.24	295	-10000	0	295
Aurora B/PP1-gamma	0.05	0.071	0.18	130	-10000	0	130
RHOA	-0.007	0.018	-10000	0	-0.31	2	2
NCAPH	0.15	0.12	0.24	354	-10000	0	354
NPM1	0	0	-10000	0	-10000	0	0
RASA1	-0.007	0.022	-10000	0	-0.31	3	3
KLHL9	-0.007	0.018	-10000	0	-0.31	2	2
mitotic prometaphase	0.012	0.004	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.046	0.065	0.17	123	-0.21	1	124
PPP1CC	0.001	0.041	0.24	16	-10000	0	16
Centraspindlin	0.42	0.12	0.43	552	-10000	0	552
RhoA/GDP	-0.004	0.012	-10000	0	-0.21	2	2
NSUN2	0.001	0.021	0.36	2	-10000	0	2
MYLK	0.014	0.091	0.16	103	-0.23	43	146
KIF23	0.24	0.044	0.25	550	-10000	0	550
VIM	0	0.11	0.2	83	-0.21	85	168
RACGAP1	0.22	0.083	0.25	488	-10000	0	488
mitosis	0	0	-10000	0	-10000	0	0
NCL	0	0	-10000	0	-10000	0	0
Chromosomal passenger complex	0.24	0.11	0.26	506	-10000	0	506
Chromosomal passenger complex/EVI5	0.008	0.024	0.23	2	-10000	0	2
TACC1	-0.25	0.12	-10000	0	-0.31	460	460
PPP2R5D	-0.006	0	-10000	0	-10000	0	0
CUL3	-0.006	0	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

Circadian rhythm pathway

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
chromatin modification	0.31	0.2	0.51	254	-10000	0	254
CLOCK	0.023	0.045	0.25	13	-10000	0	13
TIMELESS/CRY2	0.16	0.18	0.37	254	-10000	0	254
DEC1/BMAL1	0.015	0.028	0.18	5	-10000	0	5
ATR	0.046	0.1	0.24	120	-10000	0	120
NR1D1	0.11	0.22	-10000	0	-0.9	13	13
ARNTL	0.02	0.036	0.26	5	-10000	0	5
TIMELESS	0.23	0.26	0.52	254	-10000	0	254
NPAS2	0.027	0.051	0.25	21	-10000	0	21
CRY2	-0.006	0	-10000	0	-10000	0	0
mol:CO	-0.079	0.091	0.13	3	-0.18	254	257
CHEK1	0.23	0.059	0.24	534	-10000	0	534
mol:HEME	0.079	0.091	0.18	254	-0.13	3	257
PER1	-0.012	0.042	-10000	0	-0.31	11	11
BMAL/CLOCK/NPAS2	0.095	0.11	0.21	254	-10000	0	254
BMAL1/CLOCK	0.12	0.18	0.39	10	-0.56	13	23
S phase of mitotic cell cycle	0.31	0.2	0.51	254	-10000	0	254
TIMELESS/CHEK1/ATR	0.32	0.2	0.52	260	-10000	0	260
mol:NADPH	0.079	0.091	0.18	254	-0.13	3	257
PER1/TIMELESS	0.16	0.19	0.37	249	-10000	0	249
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	-0.006	0	-10000	0	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.02	0.052	-10000	0	-0.43	2	2
Crk/p130 Cas/Paxillin	-0.19	0.1	-10000	0	-0.28	276	276
JUN	-0.066	0.09	0.22	1	-0.29	2	3
HRAS	-0.006	0	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.06	0.09	0.16	11	-0.16	245	256
RAP1A	-0.005	0.01	0.24	1	-10000	0	1
FRS2	0.001	0.04	0.24	15	-10000	0	15
RAP1A/GDP	-0.003	0.007	0.17	1	-10000	0	1
RET51/GFRalpha1/GDNF/DOK1	-0.061	0.091	0.16	11	-0.16	246	257
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	-0.006	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.005	0.01	0.24	1	-10000	0	1
RET9/GFRalpha1/GDNF/Enigma	-0.063	0.087	0.15	8	-0.16	249	257
RHOA	-0.007	0.018	-10000	0	-0.31	2	2
RAP1A/GTP	-0.066	0.07	0.12	10	-0.14	244	254
GRB7	-0.006	0.03	0.24	4	-0.31	3	7
RET51/GFRalpha1/GDNF	-0.06	0.09	0.16	11	-0.16	245	256
MAPKKK cascade	-0.079	0.081	0.1	7	-0.17	230	237
BCAR1	-0.006	0.013	-10000	0	-0.31	1	1
RET9/GFRalpha1/GDNF/IRS1	-0.16	0.11	0.15	7	-0.21	448	455
lamellipodium assembly	-0.17	0.1	-10000	0	-0.26	272	272
RET51/GFRalpha1/GDNF/SHC	-0.06	0.09	0.16	11	-0.16	245	256
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
RET9/GFRalpha1/GDNF/SHC	-0.062	0.086	0.15	8	-0.16	248	256
RET9/GFRalpha1/GDNF/Shank3	-0.062	0.086	0.15	8	-0.16	248	256
MAPK3	-0.068	0.072	0.22	1	-0.27	10	11
DOK1	-0.007	0.018	-10000	0	-0.31	2	2
DOK6	-0.006	0	-10000	0	-10000	0	0
PXN	-0.01	0.033	-10000	0	-0.31	7	7
neurite development	-0.071	0.079	0.22	1	-0.33	14	15
DOK5	0.066	0.14	0.24	193	-0.31	23	216
GFRA1	-0.13	0.16	0.24	8	-0.31	248	256
MAPK8	-0.07	0.094	0.2	1	-0.39	1	2
HRAS/GTP	-0.071	0.099	0.24	1	-0.19	230	231
tube development	-0.068	0.074	0.14	8	-0.15	248	256
MAPK1	-0.065	0.068	0.22	1	-0.27	1	2
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.077	0.094	0.21	1	-0.18	241	242
Rac1/GDP	-0.004	0.009	-10000	0	-0.21	1	1
SRC	-0.006	0	-10000	0	-10000	0	0
PDLIM7	-0.007	0.018	-10000	0	-0.31	2	2
RET51/GFRalpha1/GDNF/Dok6	-0.056	0.086	0.28	1	-0.15	245	246
SHC1	-0.006	0	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.06	0.09	0.16	11	-0.16	245	256
RET51/GFRalpha1/GDNF/Dok5	-0.02	0.12	0.15	112	-0.17	166	278
PRKCA	-0.005	0.037	0.24	7	-0.31	4	11
HRAS/GDP	-0.003	0	-10000	0	-10000	0	0
CREB1	-0.091	0.11	0.2	2	-0.22	230	232
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.082	0.094	-10000	0	-0.19	248	248
RET51/GFRalpha1/GDNF/Grb7	-0.06	0.091	0.16	12	-0.16	245	257
mol:GDP	0	0	-10000	0	-10000	0	0
RET	-0.003	0.027	0.24	7	-10000	0	7
DOK4	-0.006	0	-10000	0	-10000	0	0
JNK cascade	-0.066	0.089	0.21	1	-0.29	2	3
RET9/GFRalpha1/GDNF/FRS2	-0.059	0.089	0.16	15	-0.16	241	256
SHANK3	-0.006	0	-10000	0	-10000	0	0
RASA1	-0.007	0.022	-10000	0	-0.31	3	3
NCK1	0.012	0.065	0.24	42	-10000	0	42
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.074	0.094	0.22	1	-0.18	233	234
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.076	0.095	0.22	2	-0.18	238	240
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.074	0.1	0.22	1	-0.19	233	234
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.073	0.095	0.21	2	-0.18	230	232
PI3K	-0.24	0.16	-10000	0	-0.38	272	272
SOS1	0.005	0.05	0.24	24	-10000	0	24
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.058	0.083	0.14	8	-0.15	248	256
GRB10	-0.006	0	-10000	0	-10000	0	0
activation of MAPKK activity	-0.072	0.091	0.19	2	-10000	0	2
RET51/GFRalpha1/GDNF/FRS2	-0.057	0.093	0.17	18	-0.16	238	256
GAB1	-0.007	0.018	-10000	0	-0.31	2	2
IRS1	-0.2	0.15	-10000	0	-0.31	357	357
IRS2	-0.006	0	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.08	0.095	0.21	1	-0.19	245	246
RET51/GFRalpha1/GDNF/PKC alpha	-0.06	0.094	0.16	17	-0.16	246	263
GRB2	-0.006	0	-10000	0	-10000	0	0
PRKACA	-0.006	0	-10000	0	-10000	0	0
GDNF	-0.006	0	-10000	0	-10000	0	0
RAC1	-0.006	0.013	-10000	0	-0.31	1	1
RET51/GFRalpha1/GDNF/IRS1	-0.16	0.12	0.17	10	-0.21	447	457
Rac1/GTP	-0.2	0.12	-10000	0	-0.31	272	272
RET9/GFRalpha1/GDNF	-0.071	0.093	0.15	8	-0.18	248	256
GFRalpha1/GDNF	-0.094	0.11	0.17	8	-0.21	248	256

×

TCGA08_p53

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
CDKN2A	0.11	0.1	0.2	314	-10000	0	314
TP53	0.019	0.079	0.15	1	-0.24	36	37
Senescence	0.003	0.098	0.16	2	-0.2	91	93
Apoptosis	0.003	0.098	0.16	2	-0.2	91	93
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	-0.075	0.067	0.22	1	-0.13	314	315
MDM4	0	0.038	0.24	14	-10000	0	14

×

Osteopontin-mediated events

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
IKK alpha homodimer	0.088	0.16	0.29	184	-0.25	5	189
NF kappa B1 p50/RelA/I kappa B alpha	0.07	0.18	0.32	152	-0.3	14	166
alphaV/beta3 Integrin/Osteopontin/Src	0.079	0.11	0.21	219	-0.24	8	227
AP1	0.08	0.26	0.4	172	-0.39	28	200
ILK	0.063	0.15	0.27	125	-0.39	2	127
bone resorption	-0.009	0.15	0.21	100	-0.28	50	150
PTK2B	-0.006	0.013	-10000	0	-0.31	1	1
PYK2/p130Cas	0.06	0.14	0.25	125	-0.25	6	131
ITGAV	0.017	0.058	0.25	19	-0.31	3	22
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.09	0.1	0.17	2	-0.21	233	235
alphaV/beta3 Integrin/Osteopontin	0.056	0.14	0.2	244	-0.2	72	316
MAP3K1	0.062	0.15	0.27	125	-0.21	28	153
JUN	0.005	0.044	0.24	14	-0.31	2	16
MAPK3	0.11	0.21	0.39	182	-0.34	3	185
MAPK1	0.12	0.21	0.39	185	-0.36	2	187
Rac1/GDP	-0.004	0.009	-10000	0	-0.21	1	1
NFKB1	-0.01	0.033	-10000	0	-0.31	7	7
MAPK8	0.064	0.15	0.29	125	-0.23	17	142
ITGB3	-0.024	0.12	0.26	12	-0.31	74	86
NFKBIA	0.11	0.22	0.39	183	-0.32	9	192
FOS	-0.023	0.12	0.25	26	-0.31	65	91
CD44	-0.13	0.15	-10000	0	-0.31	236	236
CHUK	0.002	0.043	0.24	18	-10000	0	18
PLAU	0.17	0.3	0.6	176	-10000	0	176
NF kappa B1 p50/RelA	0.082	0.19	0.37	150	-0.28	8	158
BCAR1	-0.006	0.013	-10000	0	-0.31	1	1
RELA	-0.006	0.013	-10000	0	-0.31	1	1
alphaV beta3 Integrin	-0.002	0.11	0.2	35	-0.22	75	110
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	0.057	0.14	0.25	125	-0.2	19	144
VAV3	0.069	0.14	0.26	148	-0.36	2	150
MAP3K14	0.095	0.18	0.32	182	-0.27	5	187
ROCK2	-0.004	0.023	0.24	5	-10000	0	5
SPP1	0.089	0.13	0.26	202	-0.32	6	208
RAC1	-0.006	0.013	-10000	0	-0.31	1	1
Rac1/GTP	0.04	0.11	0.21	112	-0.34	2	114
MMP2	0.052	0.26	0.42	117	-0.4	56	173

×

Nongenotropic Androgen signaling

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
PTK2	0.007	0.044	0.2	28	-10000	0	28
GNB1/GNG2	-0.089	0.082	-10000	0	-0.16	328	328
regulation of S phase of mitotic cell cycle	-0.12	0.13	-10000	0	-0.22	310	310
GNAO1	-0.003	0.028	0.24	6	-0.31	1	7
HRAS	-0.006	0.004	-10000	0	-10000	0	0
SHBG/T-DHT	0.003	0.002	-10000	0	-10000	0	0
PELP1	-0.006	0.004	-10000	0	-10000	0	0
AKT1	-0.003	0.009	0.2	1	-10000	0	1
MAP2K1	-0.085	0.087	0.2	13	-0.24	42	55
T-DHT/AR	-0.12	0.1	-10000	0	-0.21	329	329
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.002	0.008	26	-0.006	53	79
GNAI2	-0.005	0.002	-10000	0	-10000	0	0
GNAI3	0.036	0.093	0.24	96	-10000	0	96
GNAI1	-0.005	0.041	0.24	8	-0.31	5	13
mol:GDP	-0.2	0.17	-10000	0	-0.33	329	329
cell proliferation	-0.12	0.17	0.3	23	-0.41	97	120
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
FOS	-0.11	0.25	0.44	26	-0.75	65	91
mol:Ca2+	-0.015	0.018	0.04	15	-0.049	37	52
MAPK3	-0.12	0.14	0.3	11	-0.32	109	120
MAPK1	-0.055	0.093	0.23	23	-0.25	46	69
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
mol:IP3	0	0.003	0.011	26	-0.004	20	46
cAMP biosynthetic process	0.01	0.013	-10000	0	-10000	0	0
GNG2	-0.005	0.01	0.24	1	-10000	0	1
potassium channel inhibitor activity	0	0.003	0.011	26	-0.004	20	46
HRAS/GTP	-0.086	0.075	0.13	10	-0.15	316	326
actin cytoskeleton reorganization	-0.033	0.054	-10000	0	-0.14	107	107
SRC	-0.006	0.004	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.003	0.011	26	-0.004	20	46
PI3K	-0.003	0.099	0.15	98	-0.18	107	205
apoptosis	0.094	0.16	0.46	66	-0.34	24	90
T-DHT/AR/PELP1	-0.099	0.089	-10000	0	-0.18	329	329
HRAS/GDP	-0.19	0.16	-10000	0	-0.32	325	325
CREB1	-0.11	0.16	0.4	10	-0.5	66	76
RAC1-CDC42/GTP	-0.013	0.079	0.12	98	-0.14	107	205
AR	-0.18	0.15	-10000	0	-0.31	329	329
GNB1	-0.006	0.013	-10000	0	-0.31	1	1
RAF1	-0.085	0.08	0.17	13	-0.22	42	55
RAC1-CDC42/GDP	-0.19	0.16	-10000	0	-0.31	325	325
T-DHT/AR/PELP1/Src	-0.089	0.083	-10000	0	-0.16	328	328
MAP2K2	-0.11	0.099	0.21	10	-0.26	90	100
T-DHT/AR/PELP1/Src/PI3K	-0.12	0.13	-10000	0	-0.22	310	310
GNAZ	-0.007	0.025	-10000	0	-0.31	4	4
SHBG	-0.006	0	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.032	0.061	0.19	1	-0.26	7	8
mol:T-DHT	0	0	-10000	0	-10000	0	0
RAC1	-0.006	0.013	-10000	0	-0.31	1	1
GNRH1	-0.003	0.001	-10000	0	-10000	0	0
Gi family/GTP	-0.046	0.064	0.18	1	-0.23	8	9
CDC42	-0.006	0	-10000	0	-10000	0	0

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.02	0.065	0.18	83	-10000	0	83
ATM	0.002	0.043	0.24	18	-10000	0	18
UBE2D3	-0.006	0	-10000	0	-10000	0	0
PRKDC	0.036	0.093	0.24	97	-10000	0	97
ATR	0.046	0.1	0.24	120	-10000	0	120
UBE2L3	-0.006	0	-10000	0	-10000	0	0
FANCD2	0.11	0.12	0.34	92	-10000	0	92
protein ubiquitination	0.14	0.087	0.26	169	-10000	0	169
XRCC5	0.008	0.056	0.24	31	-10000	0	31
XRCC6	-0.006	0	-10000	0	-10000	0	0
M/R/N Complex	0.034	0.057	0.16	99	-0.18	2	101
MRE11A	0.025	0.081	0.24	70	-10000	0	70
DNA-PK	0.038	0.059	0.16	114	-10000	0	114
FA complex/FANCD2/Ubiquitin	0.004	0.03	0.28	5	-10000	0	5
FANCF	-0.006	0	-10000	0	-10000	0	0
BRCA1	0.009	0.058	0.24	33	-10000	0	33
CCNE1	0.22	0.073	0.24	515	-10000	0	515
CDK2/Cyclin E1	0.22	0.1	0.24	535	-10000	0	535
FANCG	-0.005	0.01	0.24	1	-10000	0	1
BRCA1/BACH1/BARD1	0.029	0.081	0.2	100	-10000	0	100
FANCE	-0.006	0	-10000	0	-10000	0	0
FANCC	-0.004	0.023	0.24	5	-10000	0	5
NBN	0.015	0.071	0.24	49	-0.31	1	50
FANCA	0.003	0.046	0.24	20	-10000	0	20
DNA repair	0.19	0.17	0.32	296	-10000	0	296
BRCA1/BARD1/ubiquitin	0.029	0.081	0.2	100	-10000	0	100
BARD1/DNA-PK	0.057	0.081	0.18	158	-10000	0	158
FANCL	0.011	0.062	0.24	38	-10000	0	38
mRNA polyadenylation	-0.019	0.065	-10000	0	-0.17	83	83
BRCA1/BARD1/CTIP/M/R/N Complex	0.048	0.087	0.23	75	-10000	0	75
BRCA1/BACH1/BARD1/TopBP1	0.085	0.075	0.16	297	-10000	0	297
BRCA1/BARD1/P53	0.033	0.1	0.18	140	-0.16	56	196
BARD1/CSTF1/BRCA1	0.031	0.053	0.16	86	-10000	0	86
BRCA1/BACH1	0.009	0.058	0.24	33	-10000	0	33
BARD1	0.029	0.087	0.24	81	-10000	0	81
PCNA	0.052	0.1	0.24	133	-10000	0	133
BRCA1/BARD1/UbcH5C	0.031	0.053	0.16	86	-10000	0	86
BRCA1/BARD1/UbcH7	0.031	0.053	0.16	86	-10000	0	86
BRCA1/BARD1/RAD51/PCNA	0.11	0.11	0.29	106	-10000	0	106
BARD1/DNA-PK/P53	0.035	0.1	0.31	32	-0.15	55	87
BRCA1/BARD1/Ubiquitin	0.029	0.081	0.2	100	-10000	0	100
BRCA1/BARD1/CTIP	0.04	0.093	0.19	145	-10000	0	145
FA complex	0.028	0.054	0.23	14	-10000	0	14
BARD1/EWS	0.018	0.062	0.17	81	-10000	0	81
RBBP8	0.02	0.071	0.2	74	-10000	0	74
TP53	-0.051	0.11	0.24	1	-0.31	85	86
TOPBP1	0.16	0.12	0.24	369	-10000	0	369
G1/S transition of mitotic cell cycle	-0.032	0.098	0.16	56	-0.29	26	82
BRCA1/BARD1	0.2	0.11	0.31	231	-10000	0	231
CSTF1	-0.004	0.021	0.24	4	-10000	0	4
BARD1/EWS-Fli1	0.021	0.06	0.17	81	-10000	0	81
CDK2	0.094	0.12	0.24	229	-10000	0	229
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.12	0.12	0.24	290	-10000	0	290
RAD50	-0.005	0.019	0.24	2	-0.31	1	3
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.029	0.081	0.2	100	-10000	0	100
EWSR1	-0.006	0	-10000	0	-10000	0	0

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	0.22	0.43	0.78	128	-0.9	6	134
HDAC7	0.01	0.035	0.16	14	-10000	0	14
HIF1A/ARNT/Cbp/p300/Src-1	0.024	0.3	0.8	40	-0.78	2	42
SMAD4	-0.007	0.002	-10000	0	-10000	0	0
ID2	0.22	0.43	0.79	121	-0.9	6	127
AP1	-0.015	0.092	0.2	44	-0.21	65	109
ABCG2	0.21	0.44	0.79	122	-0.87	8	130
HIF1A	0.081	0.14	0.29	122	-0.41	1	123
TFF3	0.005	0.38	0.85	43	-0.86	17	60
GATA2	-0.006	0.039	0.16	9	-0.31	6	15
AKT1	0.098	0.15	0.35	102	-10000	0	102
response to hypoxia	0.071	0.15	0.31	131	-10000	0	131
MCL1	0.22	0.43	0.79	120	-0.9	6	126
NDRG1	0.24	0.45	0.82	131	-0.92	7	138
SERPINE1	0.25	0.46	0.83	144	-0.9	6	150
FECH	0.22	0.43	0.79	120	-0.9	6	126
FURIN	0.22	0.43	0.79	120	-0.9	6	126
NCOA2	-0.005	0.015	0.24	2	-10000	0	2
EP300	0.19	0.25	0.55	142	-10000	0	142
HMOX1	0.22	0.44	0.78	128	-0.9	7	135
BHLHE40	0.18	0.43	0.76	142	-0.9	6	148
BHLHE41	0.18	0.43	0.76	142	-0.9	6	148
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.017	0.12	0.39	32	-0.28	1	33
ENG	0.1	0.15	0.35	57	-0.31	1	58
JUN	0.001	0.043	0.25	14	-0.31	1	15
RORA	0.22	0.43	0.79	120	-0.9	6	126
ABCB1	-0.022	0.073	0.69	3	-10000	0	3
TFRC	0.29	0.48	0.88	151	-0.9	6	157
CXCR4	0.22	0.44	0.8	120	-0.92	6	126
TF	0.23	0.44	0.8	122	-0.9	6	128
CITED2	0.22	0.44	0.78	126	-0.92	8	134
HIF1A/ARNT	-0.027	0.31	1	18	-1	6	24
LDHA	0.082	0.25	0.66	86	-10000	0	86
ETS1	0.23	0.44	0.8	122	-0.9	6	128
PGK1	0.3	0.49	0.92	147	-0.9	6	153
NOS2	0.18	0.43	0.76	142	-0.9	6	148
ITGB2	0.22	0.43	0.79	119	-0.89	7	126
ALDOA	0.22	0.43	0.79	120	-0.9	6	126
Cbp/p300/CITED2	0.16	0.44	0.78	135	-0.93	7	142
FOS	-0.027	0.11	0.24	26	-0.31	64	90
HK2	0.22	0.43	0.79	120	-0.9	6	126
SP1	-0.006	0.018	0.21	4	-10000	0	4
GCK	0.23	0.3	0.77	75	-10000	0	75
HK1	0.22	0.43	0.79	120	-0.9	6	126
NPM1	0.22	0.43	0.79	120	-0.9	6	126
EGLN1	0.22	0.43	0.79	120	-0.9	6	126
CREB1	0.046	0.096	0.22	131	-10000	0	131
PGM1	0.24	0.45	0.83	132	-0.9	6	138
SMAD3	-0.008	0.018	-10000	0	-0.31	2	2
EDN1	0.14	0.22	0.65	34	-1.2	1	35
IGFBP1	0.22	0.43	0.79	120	-0.9	6	126
VEGFA	0.26	0.41	0.79	135	-0.72	1	136
HIF1A/JAB1	0.004	0.062	0.22	27	-0.29	1	28
CP	0.32	0.49	0.9	160	-0.89	11	171
CXCL12	0.19	0.44	0.8	109	-0.88	11	120
COPS5	0.014	0.068	0.24	46	-10000	0	46
SMAD3/SMAD4	-0.009	0.013	-10000	0	-0.21	2	2
BNIP3	0.24	0.45	0.83	130	-0.9	6	136
EGLN3	0.24	0.46	0.83	134	-0.89	9	143
CA9	0.25	0.46	0.84	137	-0.9	6	143
TERT	0.22	0.43	0.79	120	-0.9	6	126
ENO1	0.22	0.43	0.79	120	-0.9	6	126
PFKL	0.22	0.43	0.78	128	-0.9	6	134
NCOA1	-0.007	0.018	-10000	0	-0.31	2	2
ADM	0.24	0.46	0.86	123	-0.9	6	129
ARNT	0.082	0.14	0.28	137	-10000	0	137
HNF4A	-0.006	0	-10000	0	-10000	0	0
ADFP	0.29	0.49	0.91	148	-0.93	5	153
SLC2A1	0.26	0.41	0.8	132	-0.68	2	134
LEP	0.22	0.43	0.79	120	-0.9	6	126
HIF1A/ARNT/Cbp/p300	0.031	0.32	0.85	42	-0.8	2	44
EPO	0.22	0.35	0.73	100	-0.66	1	101
CREBBP	0.18	0.25	0.55	138	-0.33	1	139
HIF1A/ARNT/Cbp/p300/HDAC7	0.017	0.28	0.75	38	-0.78	2	40
PFKFB3	0.21	0.44	0.78	126	-0.89	10	136
NT5E	0.24	0.47	0.85	132	-0.89	12	144

×

IL2 signaling events mediated by STAT5

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
GAB2	-0.006	0.061	0.24	15	-0.31	13	28
ELF1	-0.008	0.032	0.18	6	-0.31	4	10
CCNA2	0.21	0.084	0.24	494	-10000	0	494
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
JAK3	-0.006	0	-10000	0	-10000	0	0
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
JAK1	-0.007	0.018	-10000	0	-0.31	2	2
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.019	0.086	0.27	1	-10000	0	1
SHC1	-0.006	0	-10000	0	-10000	0	0
SP1	-0.22	0.13	0.18	8	-0.29	428	436
IL2RA	-0.004	0.046	0.41	6	-10000	0	6
IL2RB	-0.006	0.021	0.24	1	-0.31	2	3
SOS1	0.005	0.05	0.24	24	-10000	0	24
IL2RG	-0.009	0.09	0.24	30	-0.31	30	60
G1/S transition of mitotic cell cycle	-0.32	0.26	0.33	13	-0.46	428	441
PTPN11	-0.006	0	-10000	0	-10000	0	0
CCND2	-0.42	0.26	0.41	8	-0.56	428	436
LCK	-0.006	0	-10000	0	-10000	0	0
GRB2	-0.006	0	-10000	0	-10000	0	0
IL2	-0.006	0	-10000	0	-10000	0	0
CDK6	-0.002	0.043	0.24	13	-0.31	3	16
CCND3	-0.018	0.078	-10000	0	-10000	0	0

×

mTOR signaling pathway

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
GBL	-0.006	0	-10000	0	-10000	0	0
MKNK1	-0.006	0	-10000	0	-10000	0	0
mol:PIP3	-0.15	0.13	0.12	28	-0.24	327	355
FRAP1	-0.021	0.035	-10000	0	-10000	0	0
AKT1	-0.13	0.11	0.16	1	-0.23	277	278
INSR	-0.034	0.088	-10000	0	-0.31	53	53
Insulin Receptor/Insulin	-0.018	0.051	-10000	0	-0.18	53	53
mol:GTP	-0.11	0.093	-10000	0	-0.19	266	266
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.049	0.037	-10000	0	-10000	0	0
TSC2	-0.006	0	-10000	0	-10000	0	0
RHEB/GDP	-0.1	0.076	-10000	0	-0.17	266	266
TSC1	-0.006	0.013	-10000	0	-0.31	1	1
Insulin Receptor/IRS1	-0.18	0.15	-10000	0	-0.29	357	357
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.054	0.041	-10000	0	-0.16	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	-0.006	0	-10000	0	-10000	0	0
RPS6KB1	-0.065	0.069	0.18	1	-10000	0	1
MAP3K5	0.001	0.022	0.23	2	-0.29	2	4
PIK3R1	-0.073	0.13	-10000	0	-0.31	131	131
apoptosis	0.001	0.022	0.23	2	-0.29	2	4
mol:LY294002	-0.001	0.001	-10000	0	-0.001	357	357
EIF4B	-0.061	0.063	0.17	1	-0.2	1	2
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.059	0.059	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	-0.024	0.021	-10000	0	-10000	0	0
KIAA1303	-0.006	0	-10000	0	-10000	0	0
PI3K	-0.16	0.14	0.15	27	-0.24	406	433
mTOR/RHEB/GTP/Raptor/GBL	-0.039	0.051	-10000	0	-10000	0	0
FKBP1A	-0.004	0.005	-10000	0	-10000	0	0
RHEB/GTP	-0.098	0.078	0.12	6	-0.23	68	74
mol:Amino Acids	-0.001	0.001	-10000	0	-0.001	357	357
FKBP12/Rapamycin	-0.002	0.004	-10000	0	-10000	0	0
PDPK1	-0.14	0.12	0.16	1	-0.24	277	278
EIF4E	-0.006	0	-10000	0	-10000	0	0
ASK1/PP5C	-0.011	0.042	-10000	0	-0.57	2	2
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.009	0.028	-10000	0	-10000	0	0
TSC1/TSC2	-0.12	0.1	0.15	1	-0.2	266	267
tumor necrosis factor receptor activity	0.001	0.001	0.001	357	-10000	0	357
RPS6	-0.006	0	-10000	0	-10000	0	0
PPP5C	-0.005	0.01	0.24	1	-10000	0	1
EIF4G1	-0.006	0	-10000	0	-10000	0	0
IRS1	-0.18	0.14	-10000	0	-0.29	357	357
INS	-0.006	0	-10000	0	-10000	0	0
PTEN	-0.009	0.042	-10000	0	-0.31	11	11
PDK2	-0.14	0.12	0.16	1	-0.24	277	278
EIF4EBP1	0.006	0.01	-10000	0	-10000	0	0
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
PPP2R5D	-0.021	0.032	-10000	0	-10000	0	0
peptide biosynthetic process	-0.025	0.05	-10000	0	-0.16	67	67
RHEB	0.005	0.052	0.24	26	-10000	0	26
EIF4A1	-0.006	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0.001	0.002	11	-10000	0	11
EEF2	-0.026	0.05	-10000	0	-0.16	67	67
eIF4E/4E-BP1	0.008	0.007	-10000	0	-10000	0	0

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.11	0.083	-10000	0	-0.16	382	382
TC10/GTP	-0.019	0.034	-10000	0	-0.14	41	41
Insulin Receptor/Insulin/IRS1/Shp2	-0.11	0.098	-10000	0	-0.18	368	368
HRAS	-0.006	0	-10000	0	-10000	0	0
APS homodimer	0	0	-10000	0	-10000	0	0
GRB14	0.006	0.052	0.24	26	-10000	0	26
FOXO3	-0.033	0.084	-10000	0	-0.71	8	8
AKT1	-0.1	0.097	0.21	2	-0.26	85	87
INSR	-0.036	0.088	-10000	0	-0.31	53	53
Insulin Receptor/Insulin	-0.024	0.04	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	-0.006	0	-10000	0	-10000	0	0
SORBS1	-0.028	0.078	-10000	0	-0.31	41	41
CRK	-0.005	0.01	0.24	1	-10000	0	1
PTPN1	-0.023	0.039	-10000	0	-10000	0	0
CAV1	-0.13	0.098	0.15	2	-0.19	400	402
CBL/APS/CAP/Crk-II/C3G	-0.001	0.042	0.14	1	-0.15	41	42
Insulin Receptor/Insulin/IRS1/NCK2	-0.11	0.098	-10000	0	-0.18	368	368
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.12	0.096	-10000	0	-0.18	346	346
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	-0.13	0.14	-10000	0	-0.52	53	53
RPS6KB1	-0.093	0.093	0.2	3	-0.25	84	87
PARD6A	-0.006	0.013	-10000	0	-0.31	1	1
CBL	-0.006	0	-10000	0	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.003	0.041	-10000	0	-0.69	2	2
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.1	0.083	-10000	0	-0.26	84	84
HRAS/GTP	-0.096	0.07	-10000	0	-0.15	354	354
Insulin Receptor	-0.036	0.088	-10000	0	-0.31	53	53
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.1	0.093	-10000	0	-0.17	368	368
PRKCI	0.037	0.083	0.25	1	-10000	0	1
Insulin Receptor/Insulin/GRB14/PDK1	-0.11	0.091	-10000	0	-0.18	335	335
SHC1	-0.006	0	-10000	0	-10000	0	0
negative regulation of MAPKKK cascade	0.018	0.054	-10000	0	-0.6	2	2
PI3K	-0.11	0.11	0.12	27	-0.19	339	366
NCK2	-0.006	0	-10000	0	-10000	0	0
RHOQ	-0.004	0.018	0.24	3	-10000	0	3
mol:H2O2	-0.004	0.006	-10000	0	-10000	0	0
HRAS/GDP	-0.003	0	-10000	0	-10000	0	0
AKT2	-0.099	0.098	0.21	2	-0.26	85	87
PRKCZ	-0.034	0.03	-10000	0	-10000	0	0
SH2B2	0	0	-10000	0	-10000	0	0
SHC/SHIP	-0.1	0.077	-10000	0	-0.16	368	368
F2RL2	-0.005	0.01	0.24	1	-10000	0	1
TRIP10	-0.006	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin/Shc	-0.007	0.046	-10000	0	-0.15	53	53
TC10/GTP/CIP4/Exocyst	0.007	0.011	0.15	3	-10000	0	3
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.004	0.053	-10000	0	-10000	0	0
RAPGEF1	-0.006	0	-10000	0	-10000	0	0
RASA1	-0.007	0.022	-10000	0	-0.31	3	3
NCK1	0.012	0.065	0.24	42	-10000	0	42
CBL/APS/CAP/Crk-II	-0.003	0.044	0.15	1	-0.16	41	42
TC10/GDP	-0.003	0.012	0.17	3	-10000	0	3
Insulin Receptor/Insulin/SHC/GRB10	-0.004	0.048	-10000	0	-0.15	53	53
INPP5D	-0.11	0.082	-10000	0	-0.16	368	368
SOS1	0.005	0.05	0.24	24	-10000	0	24
SGK1	-0.012	0.009	-10000	0	-10000	0	0
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	-0.006	0	-10000	0	-10000	0	0
IRS1	-0.2	0.15	-10000	0	-0.31	357	357
p62DOK/RasGAP	0.018	0.055	-10000	0	-0.6	2	2
INS	-0.009	0.006	-10000	0	-10000	0	0
mol:PI-3-4-P2	-0.11	0.081	-10000	0	-0.16	368	368
GRB2	-0.006	0	-10000	0	-10000	0	0
EIF4EBP1	-0.095	0.091	0.2	2	-0.25	85	87
PTPRA	-0.009	0.006	-10000	0	-10000	0	0
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
TC10/GTP/CIP4	0.007	0.011	0.15	3	-10000	0	3
PDPK1	-0.006	0	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	-0.12	0.11	-10000	0	-0.2	354	354
Insulin Receptor/Insulin/IRS1	-0.11	0.096	-10000	0	-0.18	368	368
Insulin Receptor/Insulin/IRS3	-0.028	0.06	-10000	0	-0.22	53	53
Par3/Par6	0.011	0.013	0.14	4	-0.15	1	5

×

S1P3 pathway

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
PDGFRB	-0.01	0.033	-10000	0	-0.31	7	7
mol:S1P	-0.017	0.016	0.054	4	-0.03	323	327
S1P1/S1P/Gi	-0.048	0.081	0.21	5	-0.3	9	14
GNAO1	-0.023	0.035	0.24	6	-0.31	1	7
S1P/S1P3/G12/G13	-0.018	0.024	-10000	0	-0.16	1	1
AKT1	-0.053	0.078	0.21	2	-0.51	7	9
AKT3	-0.56	0.52	0.55	4	-1	323	327
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.01	0.033	-10000	0	-0.31	7	7
GNAI2	-0.025	0.019	-10000	0	-10000	0	0
GNAI3	0.02	0.095	0.23	96	-10000	0	96
GNAI1	-0.022	0.044	0.22	8	-0.33	5	13
mol:GDP	0	0	-10000	0	-10000	0	0
S1PR3	-0.019	0.019	0.066	4	-0.035	323	327
S1PR2	0	0	-10000	0	-10000	0	0
EDG1	-0.009	0.031	-10000	0	-0.31	6	6
mol:Ca2+	-0.12	0.14	0.31	5	-0.25	269	274
MAPK3	-0.12	0.13	0.31	4	-0.25	275	279
MAPK1	-0.12	0.13	0.31	4	-0.24	269	273
JAK2	-0.12	0.13	0.3	4	-0.25	268	272
CXCR4	-0.12	0.13	0.31	4	-0.24	268	272
FLT1	-0.03	0.024	-10000	0	-10000	0	0
RhoA/GDP	-0.004	0.012	-10000	0	-0.21	2	2
Rac1/GDP	-0.004	0.009	-10000	0	-0.21	1	1
SRC	-0.12	0.13	0.31	4	-0.24	269	273
S1P/S1P3/Gi	-0.12	0.14	0.32	5	-0.25	269	274
RAC1	-0.006	0.013	-10000	0	-0.31	1	1
RhoA/GTP	-0.12	0.12	0.28	4	-0.23	269	273
VEGFA	-0.008	0.071	0.21	49	-10000	0	49
S1P/S1P2/Gi	-0.067	0.09	0.23	5	-0.2	33	38
VEGFR1 homodimer/VEGFA homodimer	-0.032	0.057	0.18	26	-10000	0	26
RHOA	-0.007	0.018	-10000	0	-0.31	2	2
S1P/S1P3/Gq	-0.039	0.066	-10000	0	-0.22	59	59
GNAQ	-0.012	0.043	-10000	0	-0.31	12	12
GNAZ	-0.025	0.031	-10000	0	-0.33	4	4
G12/G13	-0.007	0.009	-10000	0	-0.21	1	1
GNA14	-0.005	0.015	0.24	2	-10000	0	2
GNA15	-0.006	0.016	0.24	1	-0.31	1	2
GNA12	-0.006	0	-10000	0	-10000	0	0
GNA13	-0.006	0.013	-10000	0	-0.31	1	1
GNA11	-0.034	0.088	-10000	0	-0.31	53	53
Rac1/GTP	-0.12	0.12	0.28	4	-0.23	269	273

×

Aurora A 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
Aurora A/GADD45A	0.11	0.055	0.27	48	-10000	0	48
BIRC5	0.044	0.099	0.24	115	-10000	0	115
NFKBIA	0.11	0.033	-10000	0	-10000	0	0
CPEB1	-0.006	0	-10000	0	-10000	0	0
AKT1	0.11	0.03	0.31	1	-10000	0	1
NDEL1	-0.006	0	-10000	0	-10000	0	0
Aurora A/BRCA1	0.014	0.057	0.24	33	-10000	0	33
NDEL1/TACC3	0.14	0.077	0.23	245	-10000	0	245
GADD45A	0.015	0.069	0.24	48	-10000	0	48
GSK3B	0.004	0.005	-10000	0	-10000	0	0
PAK1/Aurora A	0.1	0.04	0.28	18	-10000	0	18
MDM2	-0.006	0.023	0.24	2	-0.31	2	4
JUB	0.006	0.054	0.24	28	-10000	0	28
TPX2	0.19	0.031	0.2	556	-10000	0	556
TP53	0.072	0.053	0.24	3	-0.37	3	6
DLG7	0.29	0.064	0.3	537	-10000	0	537
AURKAIP1	-0.008	0.028	-10000	0	-0.31	5	5
ARHGEF7	-0.005	0.01	0.24	1	-10000	0	1
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.15	0.081	0.24	245	-10000	0	245
G2/M transition of mitotic cell cycle	0.014	0.056	0.24	33	-10000	0	33
AURKA	0.14	0.036	-10000	0	-10000	0	0
AURKB	0.062	0.046	0.15	118	-10000	0	118
CDC25B	0.11	0.035	0.19	35	-10000	0	35
G2/M transition checkpoint	0.012	0.052	0.24	28	-10000	0	28
mRNA polyadenylation	0	0.001	-10000	0	-10000	0	0
Aurora A/CPEB	0	0.001	-10000	0	-10000	0	0
Aurora A/TACC1/TRAP/chTOG	-0.01	0.082	0.24	34	-0.2	1	35
BRCA1	0.009	0.058	0.24	33	-10000	0	33
centrosome duplication	0.1	0.04	0.27	18	-10000	0	18
regulation of centrosome cycle	0.14	0.081	0.22	245	-10000	0	245
spindle assembly	-0.011	0.081	0.23	34	-0.2	1	35
TDRD7	-0.002	0.036	0.24	11	-0.31	1	12
Aurora A/RasGAP/Survivin	0.12	0.069	0.23	135	-10000	0	135
CENPA	0.076	0.035	0.13	122	-10000	0	122
Aurora A/PP2A	0.097	0.025	-10000	0	-10000	0	0
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	0.15	0.085	0.21	326	-0.28	1	327
negative regulation of DNA binding	0.073	0.053	0.24	3	-0.33	4	7
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	-0.006	0.01	0.17	2	-10000	0	2
RASA1	-0.007	0.022	-10000	0	-0.31	3	3
Ajuba/Aurora A	0.012	0.053	0.24	28	-10000	0	28
mitotic prometaphase	0.001	0.001	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.14	0.036	-10000	0	-10000	0	0
TACC1	-0.25	0.12	-10000	0	-0.31	460	460
TACC3	0.1	0.12	0.24	245	-10000	0	245
Aurora A/Antizyme1	0.056	0.057	-10000	0	-0.21	3	3
Aurora A/RasGAP	0.096	0.026	-10000	0	-10000	0	0
OAZ1	-0.1	0.14	-10000	0	-0.31	181	181
RAN	-0.006	0	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	0.004	0.005	-10000	0	-10000	0	0
GIT1	-0.005	0.01	0.24	1	-10000	0	1
GIT1/beta-PIX/PAK1	0.014	0.027	0.16	20	-10000	0	20
Importin alpha/Importin beta/TPX2	0.19	0.031	0.2	556	-10000	0	556
PPP2R5D	-0.006	0	-10000	0	-10000	0	0
Aurora A/TPX2	0.24	0.04	0.24	556	-10000	0	556
PAK1	0.002	0.043	0.24	18	-10000	0	18
CKAP5	0.072	0.12	0.24	179	-10000	0	179

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	-0.006	0	-10000	0	-10000	0	0
PTK2	0.006	0.054	0.24	28	-10000	0	28
CRKL	-0.1	0.098	-10000	0	-0.26	140	140
GRB2/SOS1/SHC	0.015	0.03	0.16	24	-10000	0	24
HRAS	-0.006	0	-10000	0	-10000	0	0
IRS1/Crk	-0.1	0.099	-10000	0	-0.26	140	140
IGF-1R heterotetramer/IGF1/PTP1B	-0.06	0.085	-10000	0	-0.2	140	140
AKT1	-0.096	0.11	-10000	0	-0.25	141	141
BAD	-0.093	0.1	-10000	0	-0.24	140	140
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.1	0.099	-10000	0	-0.26	140	140
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.1	0.099	0.12	3	-0.26	140	143
RAF1	-0.086	0.1	-10000	0	-0.33	24	24
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.086	0.1	0.14	6	-0.24	138	144
YWHAZ	-0.006	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.1	0.11	0.12	3	-0.28	140	143
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
RPS6KB1	-0.094	0.11	0.2	2	-0.25	139	141
GNB2L1	-0.006	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.077	0.09	-10000	0	-0.28	24	24
PXN	-0.01	0.033	-10000	0	-0.31	7	7
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.001	0.036	0.17	24	-10000	0	24
HRAS/GTP	-0.09	0.085	-10000	0	-0.23	138	138
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.041	0.077	0.16	12	-0.17	112	124
IGF-1R heterotetramer	-0.086	0.13	-10000	0	-0.36	107	107
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.096	0.1	-10000	0	-0.26	140	140
Crk/p130 Cas/Paxillin	-0.097	0.092	-10000	0	-0.24	145	145
IGF1R	-0.086	0.13	-10000	0	-0.36	107	107
IGF1	-0.039	0.056	0.21	3	-0.36	11	14
IRS2/Crk	-0.097	0.094	-10000	0	-0.25	140	140
PI3K	-0.097	0.13	0.14	25	-0.23	213	238
apoptosis	0.085	0.094	0.22	140	-10000	0	140
HRAS/GDP	-0.003	0	-10000	0	-10000	0	0
PRKCD	-0.096	0.12	-10000	0	-0.29	135	135
RAF1/14-3-3 E	-0.078	0.091	-10000	0	-0.29	24	24
BAD/14-3-3	-0.089	0.099	-10000	0	-0.23	140	140
PRKCZ	-0.096	0.11	-10000	0	-0.25	141	141
Crk/p130 Cas/Paxillin/FAK1	-0.097	0.091	-10000	0	-0.24	135	135
PTPN1	-0.006	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.099	0.12	-10000	0	-0.31	134	134
BCAR1	-0.006	0.013	-10000	0	-0.31	1	1
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.052	0.075	-10000	0	-0.18	140	140
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.005	0.05	0.24	24	-10000	0	24
IRS1/NCK2	-0.1	0.098	-10000	0	-0.26	140	140
GRB10	-0.006	0	-10000	0	-10000	0	0
PTPN11	-0.1	0.098	-10000	0	-0.26	140	140
IRS1	-0.069	0.12	0.1	3	-0.28	140	143
IRS2	-0.1	0.098	-10000	0	-0.26	140	140
IGF-1R heterotetramer/IGF1	-0.086	0.11	0.14	3	-0.27	140	143
GRB2	-0.006	0	-10000	0	-10000	0	0
PDPK1	-0.099	0.12	-10000	0	-0.25	155	155
YWHAE	-0.006	0.013	-10000	0	-0.31	1	1
PRKD1	-0.096	0.12	-10000	0	-0.3	133	133
SHC1	-0.006	0	-10000	0	-10000	0	0

×

Endothelins

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
AKT1	0.031	0.2	0.34	138	-0.31	12	150
PTK2B	-0.004	0.014	-10000	0	-0.31	1	1
mol:Ca2+	0.034	0.14	0.46	9	-0.53	1	10
EDN1	0.027	0.15	0.29	104	-0.26	6	110
EDN3	-0.003	0.027	0.24	7	-10000	0	7
EDN2	-0.001	0.036	0.24	12	-10000	0	12
HRAS/GDP	0.025	0.16	0.34	31	-0.35	22	53
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	0.01	0.13	0.23	92	-0.31	18	110
ADCY4	0.052	0.16	0.24	213	-0.26	12	225
ADCY5	0.052	0.16	0.25	178	-0.26	12	190
ADCY6	0.052	0.16	0.25	183	-0.26	12	195
ADCY7	0.052	0.16	0.25	177	-0.26	12	189
ADCY1	0.052	0.16	0.25	177	-0.26	12	189
ADCY2	0.052	0.16	0.25	177	-0.26	12	189
ADCY3	0.052	0.16	0.25	177	-0.26	12	189
ADCY8	-0.03	0.16	0.24	93	-0.29	67	160
ADCY9	0.041	0.17	0.25	174	-0.27	27	201
arachidonic acid secretion	-0.098	0.24	0.46	21	-0.54	77	98
ETB receptor/Endothelin-1/Gq/GTP	0.035	0.12	0.2	98	-0.27	18	116
GNAO1	-0.004	0.028	0.24	6	-0.31	1	7
HRAS	-0.005	0.004	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	0.02	0.18	0.37	100	-0.28	12	112
ETA receptor/Endothelin-1/Gs/GTP	0.03	0.17	0.35	98	-0.27	12	110
mol:GTP	0.002	0.011	-10000	0	-10000	0	0
COL3A1	0.14	0.31	0.52	203	-0.51	5	208
EDNRB	0.051	0.083	0.16	196	-10000	0	196
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.012	0.26	0.39	97	-0.43	111	208
CYSLTR1	0.05	0.22	0.42	118	-0.37	5	123
SLC9A1	0.013	0.13	0.27	95	-0.22	5	100
mol:GDP	0.028	0.17	0.36	29	-0.36	23	52
SLC9A3	0.073	0.15	0.36	21	-0.54	1	22
RAF1	0.014	0.19	0.42	29	-0.39	53	82
JUN	0.034	0.16	0.55	13	-0.79	3	16
JAK2	0.032	0.2	0.34	139	-0.32	14	153
mol:IP3	0.017	0.14	0.25	92	-0.34	14	106
ETA receptor/Endothelin-1	0.017	0.22	0.46	96	-0.36	13	109
PLCB1	0.002	0.043	0.24	16	-0.31	1	17
PLCB2	-0.003	0.01	-10000	0	-10000	0	0
ETA receptor/Endothelin-3	0.013	0.094	0.19	95	-0.17	1	96
FOS	-0.053	0.33	0.57	26	-0.87	65	91
Gai/GDP	0.03	0.056	-10000	0	-0.38	1	1
CRK	-0.003	0.011	0.24	1	-10000	0	1
mol:Ca ++	0.06	0.22	0.34	162	-0.4	16	178
BCAR1	-0.006	0.013	-10000	0	-0.31	1	1
PRKCB1	0.034	0.14	0.24	97	-0.36	12	109
GNAQ	-0.009	0.046	-10000	0	-0.31	12	12
GNAZ	-0.008	0.025	-10000	0	-0.31	4	4
GNAL	-0.006	0	-10000	0	-10000	0	0
Gs family/GDP	-0.04	0.092	-10000	0	-0.31	29	29
ETA receptor/Endothelin-1/Gq/GTP	0.01	0.15	0.26	90	-0.34	19	109
MAPK14	0.027	0.1	0.23	23	-0.27	12	35
TRPC6	0.033	0.15	0.5	6	-0.56	1	7
GNAI2	-0.006	0	-10000	0	-10000	0	0
GNAI3	0.036	0.093	0.24	96	-10000	0	96
GNAI1	-0.005	0.041	0.24	8	-0.31	5	13
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	0.031	0.11	0.24	29	-0.26	15	44
ETB receptor/Endothelin-2	0.04	0.067	0.18	41	-10000	0	41
ETB receptor/Endothelin-3	0.038	0.062	0.15	46	-10000	0	46
ETB receptor/Endothelin-1	0.044	0.15	0.34	105	-0.22	7	112
MAPK3	-0.044	0.31	0.54	26	-0.76	67	93
MAPK1	-0.038	0.29	0.54	26	-0.74	65	91
Rac1/GDP	0.025	0.16	0.34	29	-0.34	22	51
cAMP biosynthetic process	-0.008	0.16	0.23	73	-0.28	63	136
MAPK8	0.031	0.16	0.44	14	-0.47	6	20
SRC	-0.005	0.003	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	0.062	0.096	0.2	130	-0.18	2	132
p130Cas/CRK/Src/PYK2	0.029	0.16	0.39	25	-0.48	8	33
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	0.025	0.16	0.34	28	-0.39	14	42
COL1A2	0.15	0.32	0.58	179	-0.59	7	186
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	0.015	0.098	0.2	97	-0.16	2	99
mol:DAG	0.016	0.14	0.25	92	-0.34	14	106
MAP2K2	-0.027	0.25	0.48	27	-0.56	67	94
MAP2K1	-0.004	0.23	0.5	27	-0.53	62	89
EDNRA	0.018	0.14	0.27	93	-0.22	8	101
positive regulation of muscle contraction	0.024	0.16	0.29	125	-0.27	12	137
Gq family/GDP	-0.046	0.11	0.26	12	-0.39	21	33
HRAS/GTP	0.027	0.16	0.34	34	-0.36	23	57
PRKCH	0.032	0.14	0.24	95	-0.36	12	107
RAC1	-0.006	0.013	-10000	0	-0.31	1	1
PRKCA	0.033	0.14	0.31	29	-0.38	10	39
PRKCB	0.02	0.14	0.24	99	-0.32	16	115
PRKCE	0.019	0.14	0.24	99	-0.33	15	114
PRKCD	0.032	0.14	0.24	99	-0.36	13	112
PRKCG	0.032	0.14	0.3	30	-0.36	12	42
regulation of vascular smooth muscle contraction	-0.074	0.38	0.57	26	-1	65	91
PRKCQ	0.018	0.14	0.24	96	-0.35	13	109
PLA2G4A	-0.11	0.26	0.46	21	-0.59	78	99
GNA14	-0.001	0.02	0.24	2	-10000	0	2
GNA15	-0.004	0.02	0.24	1	-0.31	1	2
GNA12	-0.006	0	-10000	0	-10000	0	0
GNA11	-0.032	0.089	-10000	0	-0.31	53	53
Rac1/GTP	0.02	0.18	0.37	100	-0.28	12	112
MMP1	0.046	0.1	0.42	33	-10000	0	33

×

TCGA08_rtk_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
PDGFRA	-0.041	0.11	0.24	9	-0.31	74	83
HRAS	-0.006	0	-10000	0	-10000	0	0
EGFR	-0.03	0.083	0.24	1	-0.31	46	47
AKT	-0.054	0.12	0.2	29	-0.22	117	146
FOXO3	-0.01	0.036	-10000	0	-0.31	8	8
AKT1	-0.005	0.01	0.24	1	-10000	0	1
FOXO1	-0.009	0.031	-10000	0	-0.31	6	6
AKT3	-0.18	0.15	0.24	4	-0.31	323	327
FOXO4	-0.006	0	-10000	0	-10000	0	0
MET	0.014	0.089	0.24	59	-0.31	12	71
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
PIK3CB	0.021	0.077	0.24	62	-10000	0	62
NRAS	0.12	0.12	0.24	300	-10000	0	300
PIK3CG	0.002	0.042	0.24	17	-10000	0	17
PIK3R3	0.083	0.12	0.24	203	-10000	0	203
PIK3R2	-0.005	0.01	0.24	1	-10000	0	1
NF1	-0.02	0.063	-10000	0	-0.31	26	26
RAS	0.051	0.087	0.18	91	-0.27	6	97
ERBB2	-0.005	0.029	0.24	5	-0.31	2	7
proliferation/survival/translation	0.064	0.11	0.22	128	-0.18	16	144
PI3K	0.032	0.11	0.19	94	-0.23	31	125
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
KRAS	0.025	0.082	0.24	71	-10000	0	71
FOXO	0.025	0.051	0.18	31	-10000	0	31
AKT2	-0.004	0.023	0.24	5	-10000	0	5
PTEN	-0.012	0.042	-10000	0	-0.31	11	11

×

Coregulation of Androgen receptor activity

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
NRIP1	-0.12	0.15	-10000	0	-0.31	218	218
SVIL	-0.013	0.05	0.24	1	-0.31	15	16
ZNF318	-0.005	0.01	0.24	1	-10000	0	1
JMJD2C	-0.006	0.015	0.24	2	-10000	0	2
T-DHT/AR/Ubc9	-0.14	0.084	-10000	0	-0.2	328	328
CARM1	-0.005	0.01	0.24	1	-10000	0	1
PRDX1	-0.006	0	-10000	0	-10000	0	0
PELP1	-0.006	0	-10000	0	-10000	0	0
CTNNB1	-0.005	0.015	0.24	2	-10000	0	2
AKT1	-0.005	0.01	0.24	1	-10000	0	1
PTK2B	-0.006	0.013	-10000	0	-0.31	1	1
MED1	-0.005	0.015	0.24	2	-10000	0	2
MAK	-0.068	0.12	0.24	2	-0.31	119	121
response to oxidative stress	0	0	-10000	0	-10000	0	0
HIP1	-0.006	0	-10000	0	-10000	0	0
GSN	-0.044	0.1	-10000	0	-0.31	71	71
NCOA2	-0.005	0.015	0.24	2	-10000	0	2
NCOA6	-0.005	0.01	0.24	1	-10000	0	1
DNA-PK	0.038	0.059	0.16	114	-10000	0	114
NCOA4	-0.006	0	-10000	0	-10000	0	0
PIAS3	-0.005	0.01	0.24	1	-10000	0	1
cell proliferation	-0.17	0.25	0.23	2	-0.65	119	121
XRCC5	0.008	0.056	0.24	31	-10000	0	31
UBE3A	-0.006	0	-10000	0	-10000	0	0
T-DHT/AR/SNURF	-0.14	0.085	-10000	0	-0.2	328	328
FHL2	-0.083	0.061	0.41	2	-0.5	3	5
RANBP9	-0.005	0.018	0.24	3	-10000	0	3
JMJD1A	-0.005	0.12	0.24	86	-10000	0	86
CDK6	-0.002	0.043	0.24	13	-0.31	3	16
TGFB1I1	-0.028	0.079	-10000	0	-0.31	42	42
T-DHT/AR/CyclinD1	-0.18	0.11	-10000	0	-0.24	386	386
XRCC6	-0.006	0	-10000	0	-10000	0	0
T-DHT/AR	-0.17	0.098	-10000	0	-0.29	162	162
CTDSP1	-0.007	0.022	-10000	0	-0.31	3	3
CTDSP2	-0.007	0.018	-10000	0	-0.31	2	2
BRCA1	0.008	0.058	0.24	33	-10000	0	33
TCF4	-0.007	0.018	-10000	0	-0.31	2	2
CDKN2A	0.13	0.12	0.24	314	-10000	0	314
SRF	-0.007	0.026	0.23	2	-0.31	3	5
NKX3-1	-0.092	0.12	-10000	0	-10000	0	0
KLK3	-0.018	0.057	-10000	0	-10000	0	0
TMF1	-0.005	0.018	0.24	3	-10000	0	3
HNRNPA1	-0.006	0	-10000	0	-10000	0	0
AOF2	-0.005	0.01	0.24	1	-10000	0	1
APPL1	-0.007	0.009	0.2	1	-10000	0	1
T-DHT/AR/Caspase 8	-0.14	0.084	-10000	0	-0.2	328	328
AR	-0.21	0.14	-10000	0	-0.33	329	329
UBA3	0	0	-10000	0	-10000	0	0
PATZ1	-0.005	0.01	0.24	1	-10000	0	1
PAWR	-0.006	0	-10000	0	-10000	0	0
PRKDC	0.036	0.093	0.24	97	-10000	0	97
PA2G4	-0.005	0.01	0.24	1	-10000	0	1
UBE2I	-0.006	0	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.12	0.076	-10000	0	-0.18	328	328
RPS6KA3	-0.003	0.032	0.24	8	-0.31	1	9
T-DHT/AR/ARA70	-0.14	0.084	-10000	0	-0.2	328	328
LATS2	-0.006	0	-10000	0	-10000	0	0
T-DHT/AR/PRX1	-0.12	0.076	-10000	0	-0.18	328	328
Cyclin D3/CDK11 p58	-0.003	0	-10000	0	-10000	0	0
VAV3	0.022	0.079	0.24	65	-10000	0	65
KLK2	-0.082	0.045	-10000	0	-10000	0	0
CASP8	-0.006	0	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.13	0.077	0.15	1	-0.18	326	327
TMPRSS2	-0.34	0.38	-10000	0	-0.76	245	245
CCND1	-0.085	0.13	0.24	1	-0.31	150	151
PIAS1	-0.005	0.01	0.24	1	-10000	0	1
mol:T-DHT	-0.024	0.028	-10000	0	-0.066	128	128
CDC2L1	0	0	-10000	0	-10000	0	0
PIAS4	-0.006	0	-10000	0	-10000	0	0
T-DHT/AR/CDK6	-0.14	0.087	0.15	1	-0.2	319	320
CMTM2	-0.006	0	-10000	0	-10000	0	0
SNURF	-0.006	0.013	-10000	0	-0.31	1	1
ZMIZ1	-0.032	0.038	0.23	1	-0.31	4	5
CCND3	-0.006	0	-10000	0	-10000	0	0
TGIF1	-0.006	0	-10000	0	-10000	0	0
FKBP4	0.006	0.054	0.24	28	-10000	0	28

×

Signaling events mediated by PRL

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
CCNE1	0.22	0.073	0.24	515	-10000	0	515
mol:Halofuginone	-0.002	0.015	-10000	0	-0.18	4	4
ITGA1	0.034	0.091	0.24	92	-10000	0	92
CDKN1A	-0.015	0.081	-10000	0	-0.43	20	20
PRL-3/alpha Tubulin	-0.007	0.031	0.17	8	-0.21	7	15
mol:Ca2+	-0.014	0.058	0.28	7	-0.2	35	42
AGT	-0.02	0.064	-10000	0	-0.31	27	27
CCNA2	0.056	0.094	0.26	2	-0.65	4	6
TUBA1B	-0.006	0	-10000	0	-10000	0	0
EGR1	-0.083	0.1	0.2	3	-0.22	215	218
CDK2/Cyclin E1	0.16	0.11	0.27	204	-0.31	12	216
MAPK3	-0.012	0.047	0.2	8	-0.22	20	28
PRL-2 /Rab GGTase beta	0.074	0.088	0.17	260	-10000	0	260
MAPK1	-0.007	0.035	0.2	9	-0.21	8	17
PTP4A1	-0.067	0.092	-10000	0	-0.71	4	4
PTP4A3	-0.006	0.045	0.24	8	-0.31	7	15
PTP4A2	-0.006	0	-10000	0	-10000	0	0
ITGB1	-0.004	0.037	0.2	13	-0.21	6	19
SRC	-0.006	0	-10000	0	-10000	0	0
RAC1	-0.007	0.063	-10000	0	-0.41	12	12
Rab GGTase beta/Rab GGTase alpha	0.074	0.088	0.17	260	-10000	0	260
PRL-1/ATF-5	-0.064	0.087	-10000	0	-0.68	4	4
RABGGTA	-0.006	0	-10000	0	-10000	0	0
BCAR1	-0.005	0.038	0.28	7	-0.17	9	16
RHOC	-0.006	0.06	-10000	0	-0.4	11	11
RHOA	-0.007	0.063	-10000	0	-0.4	13	13
cell motility	-0.035	0.07	-10000	0	-0.41	11	11
PRL-1/alpha Tubulin	-0.065	0.086	-10000	0	-0.68	4	4
PRL-3/alpha1 Integrin	0.022	0.071	0.17	99	-0.21	6	105
ROCK1	-0.035	0.07	-10000	0	-0.41	11	11
RABGGTB	0.11	0.12	0.24	260	-10000	0	260
CDK2	0.094	0.12	0.24	229	-10000	0	229
mitosis	-0.067	0.092	-10000	0	-0.71	4	4
ATF5	-0.005	0.019	0.24	2	-0.31	1	3

×

PDGFR-alpha signaling pathway

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
PDGFRA	-0.043	0.11	0.24	9	-0.32	73	82
PDGF/PDGFRA/CRKL	-0.031	0.074	0.16	9	-0.21	73	82
positive regulation of JUN kinase activity	-0.005	0.066	0.15	20	-0.16	70	90
CRKL	-0.006	0	-10000	0	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.031	0.074	0.16	9	-0.21	73	82
AP1	-0.084	0.27	0.53	26	-0.76	65	91
mol:IP3	-0.03	0.086	0.19	17	-0.22	71	88
PLCG1	-0.03	0.086	0.19	17	-0.22	71	88
PDGF/PDGFRA/alphaV Integrin	-0.026	0.085	0.18	27	-0.21	76	103
RAPGEF1	-0.006	0	-10000	0	-10000	0	0
CRK	-0.005	0.01	0.24	1	-10000	0	1
mol:Ca2+	-0.03	0.085	0.19	17	-0.22	71	88
CAV3	-0.006	0	-10000	0	-10000	0	0
CAV1	-0.053	0.11	0.24	2	-0.31	90	92
SHC/Grb2/SOS1	-0.005	0.067	0.15	20	-0.16	70	90
PDGF/PDGFRA/Shf	-0.031	0.074	0.16	9	-0.21	73	82
FOS	-0.084	0.27	0.53	25	-0.75	65	90
JUN	-0.006	0.051	0.22	16	-0.24	2	18
oligodendrocyte development	-0.026	0.085	0.18	27	-0.21	76	103
GRB2	-0.006	0	-10000	0	-10000	0	0
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
mol:DAG	-0.03	0.086	0.19	17	-0.22	71	88
PDGF/PDGFRA	-0.043	0.11	0.24	9	-0.32	73	82
actin cytoskeleton reorganization	-0.031	0.074	0.16	9	-0.21	73	82
SRF	-0.005	0.019	-10000	0	-0.21	3	3
SHC1	-0.006	0	-10000	0	-10000	0	0
PI3K	-0.032	0.12	0.16	95	-0.21	146	241
PDGF/PDGFRA/Crk/C3G	-0.026	0.061	0.15	9	-0.18	72	81
JAK1	-0.031	0.076	0.19	9	-0.21	75	84
ELK1/SRF	-0.035	0.062	-10000	0	-0.19	71	71
SHB	-0.006	0	-10000	0	-10000	0	0
SHF	-0.006	0	-10000	0	-10000	0	0
CSNK2A1	0	0.021	-10000	0	-10000	0	0
GO:0007205	-0.033	0.097	0.2	15	-0.26	71	86
SOS1	0.005	0.05	0.24	24	-10000	0	24
Ras protein signal transduction	-0.005	0.066	0.15	20	-0.16	70	90
PDGF/PDGFRA/SHB	-0.031	0.074	0.16	9	-0.21	73	82
PDGF/PDGFRA/Caveolin-1	-0.062	0.11	0.18	10	-0.25	139	149
ITGAV	0.001	0.05	0.24	19	-0.31	3	22
ELK1	-0.032	0.092	0.18	33	-0.23	71	104
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
PDGF/PDGFRA/Crk	-0.03	0.073	0.16	9	-0.21	72	81
JAK-STAT cascade	-0.031	0.075	0.19	9	-0.21	75	84
cell proliferation	-0.031	0.074	0.16	9	-0.21	73	82

×

Syndecan-1-mediated signaling events

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
TGFB1	-0.054	0.11	-10000	0	-0.31	90	90
CCL5	-0.029	0.088	0.24	6	-0.31	48	54
SDCBP	-0.006	0.023	0.24	2	-0.31	2	4
FGFR/FGF2/Syndecan-1	-0.04	0.15	0.23	35	-0.38	55	90
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	-0.046	0.14	0.2	35	-0.36	55	90
Syndecan-1/Syntenin	-0.046	0.14	0.2	35	-0.36	55	90
MAPK3	-0.048	0.14	0.18	33	-0.33	61	94
HGF/MET	0.008	0.065	0.17	62	-0.21	12	74
TGFB1/TGF beta receptor Type II	-0.054	0.11	-10000	0	-0.31	90	90
BSG	-0.006	0	-10000	0	-10000	0	0
keratinocyte migration	-0.045	0.14	0.2	35	-0.36	55	90
Syndecan-1/RANTES	-0.053	0.16	0.2	37	-0.38	68	105
Syndecan-1/CD147	-0.048	0.14	0.18	29	-0.35	55	84
Syndecan-1/Syntenin/PIP2	-0.056	0.12	-10000	0	-0.35	55	55
LAMA5	-0.005	0.01	0.24	1	-10000	0	1
positive regulation of cell-cell adhesion	-0.056	0.12	-10000	0	-0.34	55	55
MMP7	-0.1	0.16	0.24	21	-0.31	200	221
HGF	-0.004	0.021	0.24	4	-10000	0	4
Syndecan-1/CASK	-0.046	0.14	0.2	35	-0.36	55	90
Syndecan-1/HGF/MET	-0.035	0.15	0.21	49	-0.34	58	107
regulation of cell adhesion	-0.049	0.13	0.18	33	-0.32	60	93
HPSE	0.001	0.041	0.24	16	-10000	0	16
positive regulation of cell migration	-0.04	0.15	0.23	35	-0.38	55	90
SDC1	-0.041	0.16	0.23	35	-0.38	55	90
Syndecan-1/Collagen	-0.04	0.15	0.23	35	-0.38	55	90
PPIB	-0.006	0	-10000	0	-10000	0	0
MET	0.014	0.089	0.24	59	-0.31	12	71
PRKACA	-0.006	0	-10000	0	-10000	0	0
MMP9	0.034	0.091	0.24	92	-10000	0	92
MAPK1	-0.045	0.13	0.18	34	-0.34	55	89
homophilic cell adhesion	-0.045	0.15	0.23	35	-0.37	55	90
MMP1	0.047	0.1	0.24	121	-10000	0	121

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	0.009	0.052	0.17	50	-10000	0	50
alphaV beta3 Integrin	-0.014	0.08	0.16	24	-0.19	83	107
PTK2	-0.018	0.12	0.26	9	-0.29	66	75
IGF1R	-0.07	0.12	-10000	0	-0.31	121	121
PI4KB	-0.004	0.021	0.24	4	-10000	0	4
MFGE8	-0.015	0.068	0.24	8	-0.31	24	32
SRC	-0.006	0	-10000	0	-10000	0	0
CDKN1B	-0.016	0.045	0.16	4	-0.4	3	7
VEGFA	0.016	0.069	0.24	49	-10000	0	49
ILK	-0.016	0.032	-10000	0	-10000	0	0
ROCK1	-0.005	0.01	0.24	1	-10000	0	1
AKT1	-0.017	0.029	-10000	0	-10000	0	0
PTK2B	-0.013	0.074	0.26	7	-0.16	73	80
alphaV/beta3 Integrin/JAM-A	-0.025	0.07	0.16	27	-0.29	6	33
CBL	-0.006	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.011	0.075	0.16	25	-0.18	77	102
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.13	0.12	0.15	3	-0.2	381	384
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.012	0.074	0.2	7	-0.35	4	11
alphaV/beta3 Integrin/Syndecan-1	-0.01	0.076	0.16	28	-0.18	77	105
PI4KA	-0.004	0.018	0.24	3	-10000	0	3
IGF-1R heterotetramer/IGF1/IRS1	-0.12	0.11	-10000	0	-0.2	312	312
PI4 Kinase	-0.005	0.02	0.17	7	-10000	0	7
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
alphaV/beta3 Integrin/Osteopontin	0.034	0.11	0.16	195	-0.18	74	269
RPS6KB1	-0.098	0.12	0.22	6	-0.28	107	113
TLN1	-0.006	0.013	-10000	0	-0.31	1	1
MAPK3	-0.093	0.15	0.2	3	-0.41	85	88
GPR124	-0.014	0.048	-10000	0	-0.31	15	15
MAPK1	-0.09	0.14	0.2	3	-0.41	83	86
PXN	-0.01	0.033	-10000	0	-0.31	7	7
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
alphaV/beta3 Integrin/Tumstatin	-0.011	0.075	0.16	25	-0.18	78	103
cell adhesion	-0.03	0.086	0.18	26	-0.2	90	116
ANGPTL3	-0.005	0.01	0.24	1	-10000	0	1
VEGFR2 homodimer/VEGFA homodimer/Src	0.021	0.041	0.16	49	-10000	0	49
IGF-1R heterotetramer	-0.07	0.12	-10000	0	-0.31	121	121
Rac1/GDP	-0.004	0.009	-10000	0	-0.21	1	1
TGFBR2	-0.01	0.036	-10000	0	-0.31	8	8
ITGB3	-0.041	0.11	0.24	12	-0.31	77	89
IGF1	-0.016	0.06	0.24	3	-0.31	21	24
RAC1	-0.006	0.013	-10000	0	-0.31	1	1
regulation of cell-matrix adhesion	-0.016	0.079	0.16	24	-0.18	90	114
apoptosis	0.001	0.05	0.24	19	-0.31	3	22
CD47	0.007	0.057	0.24	30	-0.31	1	31
alphaV/beta3 Integrin/CD47	-0.004	0.081	0.16	49	-0.18	76	125
VCL	-0.005	0.015	0.24	2	-10000	0	2
alphaV/beta3 Integrin/Del1	0.008	0.092	0.16	95	-0.18	75	170
CSF1	-0.018	0.06	0.24	1	-0.31	23	24
PIK3C2A	-0.016	0.036	0.16	1	-0.35	1	2
PI4 Kinase/Pyk2	-0.033	0.047	-10000	0	-0.26	6	6
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.006	0.083	0.16	67	-0.16	72	139
FAK1/Vinculin	-0.014	0.098	0.24	9	-0.24	66	75
alphaV beta3/Integrin/ppsTEM5	-0.016	0.08	0.16	24	-0.18	90	114
RHOA	-0.007	0.018	-10000	0	-0.31	2	2
VTN	-0.006	0	-10000	0	-10000	0	0
BCAR1	-0.006	0.013	-10000	0	-0.31	1	1
FGF2	-0.011	0.04	-10000	0	-0.31	10	10
F11R	-0.01	0.028	0.2	1	-0.21	10	11
alphaV/beta3 Integrin/Lactadherin	-0.016	0.086	0.16	30	-0.19	92	122
alphaV/beta3 Integrin/TGFBR2	-0.013	0.079	0.16	24	-0.19	80	104
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.008	0.046	0.15	19	-0.17	25	44
HSP90AA1	-0.006	0.013	-10000	0	-0.31	1	1
alphaV/beta3 Integrin/Talin	-0.008	0.072	0.16	28	-0.16	78	106
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.075	0.13	0.24	200	-0.31	12	212
alphaV/beta3 Integrin/Pyk2	-0.01	0.078	0.18	29	-0.16	73	102
SDC1	-0.004	0.021	0.24	4	-10000	0	4
VAV3	0.005	0.064	0.15	62	-0.29	1	63
PTPN11	-0.006	0	-10000	0	-10000	0	0
IRS1	-0.2	0.15	-10000	0	-0.31	357	357
FAK1/Paxillin	-0.016	0.099	0.24	9	-0.24	67	76
cell migration	-0.015	0.094	0.23	9	-0.22	67	76
ITGAV	0.001	0.05	0.24	19	-0.31	3	22
PI3K	-0.03	0.1	0.14	89	-0.28	22	111
SPP1	0.079	0.12	0.24	202	-0.31	6	208
KDR	-0.005	0.015	0.24	2	-10000	0	2
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.001	0.05	0.24	19	-0.31	3	22
COL4A3	-0.006	0	-10000	0	-10000	0	0
angiogenesis	-0.087	0.16	0.21	3	-0.43	84	87
Rac1/GTP	0.002	0.059	0.14	62	-0.27	1	63
EDIL3	0.029	0.087	0.24	81	-10000	0	81
cell proliferation	-0.013	0.079	0.16	24	-0.19	80	104

×

LPA receptor mediated 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
GNB1/GNG2	-0.016	0.06	0.15	1	-0.17	72	73
NF kappa B1 p50/RelA/I kappa B alpha	-0.035	0.083	0.2	2	-0.24	40	42
AP1	-0.023	0.085	0.15	47	-0.16	109	156
mol:PIP3	-0.059	0.082	-10000	0	-0.16	184	184
AKT1	-0.03	0.088	0.16	32	-0.24	25	57
PTK2B	-0.019	0.073	0.16	32	-0.17	72	104
RHOA	-0.005	0.052	-10000	0	-0.37	2	2
PIK3CB	0.024	0.077	0.24	62	-10000	0	62
mol:Ca2+	-0.033	0.066	0.11	2	-0.16	89	91
MAGI3	0.001	0.038	0.24	14	-10000	0	14
RELA	-0.005	0.013	-10000	0	-0.31	1	1
apoptosis	-0.01	0.081	0.19	40	-0.18	70	110
HRAS/GDP	-0.003	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.021	0.065	0.14	32	-0.16	68	100
NF kappa B1 p50/RelA	-0.034	0.095	0.16	53	-0.19	80	133
endothelial cell migration	-0.03	0.17	0.42	32	-0.41	71	103
ADCY4	-0.004	0.094	0.2	34	-0.21	61	95
ADCY5	-0.004	0.094	0.2	34	-0.21	61	95
ADCY6	-0.005	0.094	0.2	34	-0.21	61	95
ADCY7	-0.005	0.094	0.2	34	-0.21	61	95
ADCY1	-0.005	0.094	0.2	34	-0.21	61	95
ADCY2	-0.005	0.094	0.2	34	-0.21	61	95
ADCY3	-0.004	0.094	0.2	34	-0.21	61	95
ADCY8	-0.071	0.11	0.19	12	-0.2	186	198
ADCY9	-0.015	0.11	0.2	34	-0.22	87	121
GSK3B	-0.021	0.07	0.15	32	-0.17	72	104
arachidonic acid secretion	-0.006	0.088	0.19	34	-0.2	61	95
GNG2	-0.002	0.011	0.24	1	-10000	0	1
TRIP6	-0.007	0.026	-10000	0	-0.3	3	3
GNAO1	-0.013	0.088	0.22	37	-0.19	71	108
HRAS	-0.006	0	-10000	0	-10000	0	0
NFKBIA	-0.037	0.085	0.13	30	-0.24	42	72
GAB1	-0.007	0.018	-10000	0	-0.31	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	0.006	0.036	-10000	0	-0.84	1	1
JUN	0	0.042	0.24	14	-0.31	2	16
LPA/LPA2/NHERF2	-0.033	0.064	-10000	0	-0.14	135	135
TIAM1	0.004	0.043	-10000	0	-0.98	1	1
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
mol:IP3	-0.033	0.067	0.11	2	-0.16	89	91
PLCB3	-0.027	0.063	0.1	2	-0.16	79	81
FOS	-0.028	0.11	0.24	26	-0.31	65	91
positive regulation of mitosis	-0.006	0.088	0.19	34	-0.2	61	95
LPA/LPA1-2-3	-0.019	0.057	-10000	0	-0.17	71	71
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0.001	-10000	0	-10000	0	0
BCAR1	-0.006	0.013	-10000	0	-0.31	1	1
stress fiber formation	-0.014	0.081	0.18	32	-0.22	28	60
GNAZ	-0.015	0.088	0.23	32	-0.19	74	106
EGFR/PI3K-beta/Gab1	-0.06	0.085	-10000	0	-0.17	184	184
positive regulation of dendritic cell cytokine production	-0.019	0.057	-10000	0	-0.17	71	71
LPA/LPA2/MAGI-3	-0.006	0.031	0.15	10	-10000	0	10
ARHGEF1	-0.016	0.072	0.19	32	-0.16	71	103
GNAI2	-0.014	0.086	0.23	32	-0.19	71	103
GNAI3	0.015	0.11	0.19	117	-0.19	63	180
GNAI1	-0.013	0.09	0.22	38	-0.2	72	110
LPA/LPA3	-0.011	0.029	-10000	0	-0.087	71	71
LPA/LPA2	-0.011	0.029	-10000	0	-0.087	71	71
LPA/LPA1	-0.029	0.075	-10000	0	-0.23	71	71
HB-EGF/EGFR	0.007	0.077	0.15	87	-0.18	40	127
HBEGF	0.029	0.08	0.2	93	-10000	0	93
mol:DAG	-0.033	0.067	0.11	2	-0.16	89	91
cAMP biosynthetic process	-0.016	0.092	0.18	34	-0.22	62	96
NFKB1	-0.009	0.034	-10000	0	-0.31	7	7
SRC	-0.006	0	-10000	0	-10000	0	0
GNB1	-0.003	0.014	-10000	0	-0.31	1	1
LYN	-0.038	0.085	0.13	30	-0.24	46	76
GNAQ	-0.007	0.044	0.1	32	-0.19	12	44
LPAR2	0	0.001	-10000	0	-10000	0	0
LPAR3	0	0.001	-10000	0	-10000	0	0
LPAR1	-0.011	0.057	0.13	32	-0.14	71	103
IL8	0.018	0.2	0.47	62	-0.35	42	104
PTK2	-0.002	0.08	0.18	55	-0.16	68	123
Rac1/GDP	-0.004	0.009	-10000	0	-0.21	1	1
CASP3	-0.01	0.081	0.19	40	-0.18	70	110
EGFR	-0.028	0.084	0.25	1	-0.31	46	47
PLCG1	-0.013	0.051	0.098	30	-0.12	53	83
PLD2	-0.01	0.072	0.19	32	-0.16	71	103
G12/G13	-0.023	0.058	-10000	0	-0.17	72	72
PI3K-beta	-0.05	0.072	-10000	0	-0.26	27	27
cell migration	-0.005	0.044	0.18	2	-0.27	1	3
SLC9A3R2	-0.047	0.1	-10000	0	-0.31	79	79
PXN	-0.015	0.082	0.18	32	-0.22	28	60
HRAS/GTP	-0.006	0.088	0.19	33	-0.2	61	94
RAC1	-0.006	0.013	-10000	0	-0.31	1	1
MMP9	0.035	0.091	0.24	92	-10000	0	92
PRKCE	-0.003	0.011	0.24	1	-10000	0	1
PRKCD	-0.033	0.065	0.11	3	-0.16	84	87
Gi(beta/gamma)	-0.003	0.09	0.2	34	-0.2	61	95
mol:LPA	-0.011	0.057	0.13	32	-0.14	71	103
TRIP6/p130 Cas/FAK1/Paxillin	-0.013	0.083	0.18	32	-0.2	20	52
MAPKKK cascade	-0.006	0.088	0.19	34	-0.2	61	95
contractile ring contraction involved in cytokinesis	-0.005	0.052	-10000	0	-0.37	2	2
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.003	0.035	0.1	33	-10000	0	33
GNA15	-0.004	0.036	0.1	33	-0.25	1	34
GNA12	-0.006	0	-10000	0	-10000	0	0
GNA13	-0.006	0.013	-10000	0	-0.31	1	1
MAPT	-0.022	0.067	0.14	32	-0.16	68	100
GNA11	-0.02	0.064	0.1	30	-0.19	51	81
Rac1/GTP	0.007	0.039	-10000	0	-0.89	1	1
MMP2	-0.03	0.18	0.43	32	-0.41	71	103

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	-0.011	0.073	0.24	16	-0.31	23	39
EPHB2	0.002	0.033	0.24	10	-10000	0	10
EFNB1	-0.005	0.014	-10000	0	-0.21	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0	0.036	0.18	7	-10000	0	7
Ephrin B2/EPHB1-2	0.012	0.051	0.16	36	-0.15	23	59
neuron projection morphogenesis	-0.006	0.017	-10000	0	-0.14	4	4
Ephrin B1/EPHB1-2/Tiam1	0.003	0.038	0.16	22	-0.15	3	25
DNM1	-0.003	0.014	-10000	0	-0.31	1	1
cell-cell signaling	0.001	0.003	-10000	0	-10000	0	0
MAP2K4	-0.11	0.21	0.24	1	-0.5	123	124
YES1	-0.14	0.3	0.24	2	-0.72	123	125
Ephrin B1/EPHB1-2/NCK2	0.002	0.036	0.16	20	-0.15	2	22
PI3K	-0.1	0.24	0.25	9	-0.52	123	132
mol:GDP	0.002	0.037	0.16	22	-0.15	3	25
ITGA2B	-0.006	0	-10000	0	-10000	0	0
endothelial cell proliferation	-0.004	0.044	0.15	16	-0.17	23	39
FYN	-0.16	0.31	-10000	0	-0.74	123	123
MAP3K7	-0.11	0.22	0.27	1	-0.53	123	124
FGR	-0.14	0.3	-10000	0	-0.71	123	123
TIAM1	-0.005	0.019	0.24	2	-0.31	1	3
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
RGS3	-0.006	0	-10000	0	-10000	0	0
cell adhesion	-0.12	0.23	0.24	11	-0.5	130	141
LYN	-0.15	0.31	-10000	0	-0.72	123	123
Ephrin B1/EPHB1-2/Src Family Kinases	-0.14	0.28	-10000	0	-0.66	123	123
Ephrin B1/EPHB1-2	-0.12	0.24	-10000	0	-0.57	123	123
SRC	-0.14	0.3	-10000	0	-0.71	123	123
ITGB3	-0.041	0.11	0.24	12	-0.31	77	89
EPHB1	0.003	0.035	0.24	12	-10000	0	12
EPHB4	-0.006	0	-10000	0	-10000	0	0
RAC1	-0.006	0.013	-10000	0	-0.31	1	1
Ephrin B2/EPHB4	-0.004	0.044	0.16	16	-0.17	23	39
alphaIIb/beta3 Integrin	-0.031	0.076	0.17	12	-0.21	77	89
BLK	-0.14	0.3	-10000	0	-0.71	123	123
HCK	-0.14	0.3	-10000	0	-0.71	123	123
regulation of stress fiber formation	-0.002	0.035	0.15	2	-0.16	20	22
MAPK8	-0.1	0.2	0.22	1	-0.48	123	124
Ephrin B1/EPHB1-2/RGS3	0.002	0.036	0.16	20	-0.15	2	22
endothelial cell migration	-0.095	0.19	0.22	1	-0.44	123	124
NCK2	-0.006	0	-10000	0	-10000	0	0
PTPN13	-0.074	0.19	0.23	32	-0.42	123	155
regulation of focal adhesion formation	-0.002	0.035	0.15	2	-0.16	20	22
chemotaxis	-0.002	0.035	0.15	2	-0.16	20	22
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
Rac1/GTP	-0.001	0.032	0.13	22	-10000	0	22
angiogenesis	-0.12	0.24	-10000	0	-0.57	123	123
LCK	-0.14	0.3	-10000	0	-0.71	123	123

×

IL1-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
UBC13/UEV1A	-0.004	0.009	-10000	0	-0.21	1	1
PRKCZ	-0.006	0	-10000	0	-10000	0	0
MAP3K7IP2	-0.004	0.018	0.24	3	-10000	0	3
ERC1	-0.005	0.024	0.24	4	-0.31	1	5
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.004	0.058	0.23	14	-0.21	1	15
IRAK/TOLLIP	-0.007	0.013	0.14	3	-0.16	1	4
IKBKB	-0.005	0.015	0.24	2	-10000	0	2
IKBKG	-0.006	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.001	0.045	0.19	23	-0.21	6	29
IL1A	-0.001	0.036	0.24	12	-10000	0	12
IL1B	-0.004	0.094	0.21	56	-0.21	52	108
IRAK/TRAF6/p62/Atypical PKCs	0.053	0.071	-10000	0	-10000	0	0
IL1R2	-0.003	0.049	0.24	13	-0.31	6	19
IL1R1	-0.12	0.15	-10000	0	-0.31	225	225
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.061	0.12	0.18	12	-0.23	150	162
TOLLIP	-0.006	0	-10000	0	-10000	0	0
TICAM2	-0.006	0.016	0.24	1	-0.31	1	2
MAP3K3	-0.006	0	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.011	0.018	0.16	9	-10000	0	9
IKK complex/ELKS	0.002	0.034	-10000	0	-0.28	1	1
JUN	0.008	0.051	0.22	8	-10000	0	8
MAP3K7	-0.003	0.025	0.24	6	-10000	0	6
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.041	0.15	0.28	32	-0.3	57	89
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.022	0.1	0.15	82	-0.16	164	246
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.01	0.1	0.28	9	-0.15	148	157
IL1 beta fragment/IL1R1/IL1RAP	-0.033	0.12	0.16	104	-0.18	181	285
NFKB1	-0.01	0.033	-10000	0	-0.31	7	7
MAPK8	0.008	0.052	0.23	7	-10000	0	7
IRAK1	-0.005	0.014	0.17	3	-0.17	1	4
IL1RN/IL1R1	-0.083	0.11	0.17	14	-0.21	224	238
IRAK4	0.015	0.069	0.24	48	-10000	0	48
PRKCI	0.1	0.12	0.24	255	-10000	0	255
TRAF6	-0.005	0.015	0.24	2	-10000	0	2
PI3K	-0.015	0.12	0.17	98	-0.21	107	205
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.032	0.12	0.2	23	-0.29	24	47
CHUK	0.002	0.043	0.24	18	-10000	0	18
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.033	0.12	0.16	104	-0.18	181	285
IL1 beta/IL1R2	-0.015	0.072	0.19	29	-0.18	58	87
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.009	0.022	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.077	0.094	-10000	0	-0.25	87	87
IRAK3	0.004	0.048	0.24	22	-10000	0	22
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.024	0.12	0.17	93	-0.26	28	121
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.037	0.1	0.22	9	-10000	0	9
IL1 alpha/IL1R1/IL1RAP	-0.025	0.11	0.16	82	-0.18	164	246
RELA	-0.006	0.013	-10000	0	-0.31	1	1
MAP3K7IP1	-0.006	0	-10000	0	-10000	0	0
SQSTM1	-0.006	0	-10000	0	-10000	0	0
MYD88	-0.006	0	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	-0.008	0.015	0.14	5	-0.15	1	6
IL1RAP	0.052	0.11	0.24	135	-0.31	1	136
UBE2N	-0.006	0.013	-10000	0	-0.31	1	1
IRAK/TRAF6	-0.054	0.068	-10000	0	-0.24	29	29
CASP1	-0.025	0.1	0.24	19	-0.31	52	71
IL1RN/IL1R2	0	0.044	0.17	28	-0.21	6	34
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.033	0.12	0.16	76	-0.27	28	104
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.081	0.14	-10000	0	-0.28	147	147
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
IL1RN	0.001	0.04	0.24	15	-10000	0	15
TRAF6/TAK1/TAB1/TAB2	0.012	0.017	-10000	0	-0.14	1	1
MAP2K6	0.012	0.057	0.14	82	-10000	0	82

×

Reelin signaling pathway

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
CDK5R1/CDK5	0.013	0.056	0.17	65	-10000	0	65
VLDLR	-0.014	0.055	0.24	3	-0.31	17	20
CRKL	-0.006	0	-10000	0	-10000	0	0
LRPAP1	-0.006	0.025	0.24	3	-0.31	2	5
FYN	-0.047	0.1	0.24	1	-0.31	79	80
ITGA3	-0.031	0.088	0.24	3	-0.31	50	53
RELN/VLDLR/Fyn	-0.046	0.1	0.16	22	-0.19	171	193
MAPK8IP1/MKK7/MAP3K11/JNK1	0.015	0.018	-10000	0	-0.15	1	1
AKT1	-0.049	0.11	0.2	3	-0.2	170	173
MAP2K7	-0.006	0	-10000	0	-10000	0	0
RAPGEF1	-0.006	0	-10000	0	-10000	0	0
DAB1	-0.006	0	-10000	0	-10000	0	0
RELN/LRP8/DAB1	-0.013	0.072	0.15	26	-0.16	96	122
LRPAP1/LRP8	-0.005	0.025	0.17	9	-0.21	2	11
RELN/LRP8/DAB1/Fyn	-0.032	0.087	0.15	23	-0.16	159	182
DAB1/alpha3/beta1 Integrin	-0.049	0.062	-10000	0	-0.26	8	8
long-term memory	-0.044	0.084	0.15	22	-0.28	14	36
DAB1/LIS1	-0.032	0.064	-10000	0	-0.28	2	2
DAB1/CRLK/C3G	-0.039	0.053	-10000	0	-0.15	110	110
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
DAB1/NCK2	-0.013	0.072	0.24	1	-0.28	2	3
ARHGEF2	-0.005	0.015	0.24	2	-10000	0	2
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	-0.001	0.058	0.24	20	-0.31	8	28
CDK5R1	-0.006	0	-10000	0	-10000	0	0
RELN	-0.048	0.13	0.24	22	-0.31	97	119
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
RELN/LRP8/Fyn	-0.041	0.099	0.16	22	-0.19	159	181
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.029	0.094	0.28	2	-0.16	159	161
MAPK8	-0.003	0.025	0.24	6	-10000	0	6
RELN/VLDLR/DAB1	-0.019	0.075	0.15	24	-0.16	112	136
ITGB1	-0.003	0.025	0.24	6	-10000	0	6
MAP1B	-0.048	0.083	0.18	2	-0.18	98	100
RELN/LRP8	-0.016	0.081	0.16	28	-0.18	97	125
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.031	0.089	0.28	1	-0.16	159	160
PI3K	-0.015	0.12	0.17	98	-0.21	107	205
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	-0.022	0.063	0.17	9	-0.21	50	59
RAP1A	-0.034	0.059	0.21	1	-0.26	2	3
PAFAH1B1	-0.005	0.015	0.24	2	-10000	0	2
MAPK8IP1	-0.005	0.01	0.24	1	-10000	0	1
CRLK/C3G	-0.007	0	-10000	0	-10000	0	0
GRIN2B	-0.005	0.015	0.24	2	-10000	0	2
NCK2	-0.006	0	-10000	0	-10000	0	0
neuron differentiation	-0.043	0.083	0.18	1	-0.34	13	14
neuron adhesion	-0.045	0.066	0.2	1	-0.26	7	8
LRP8	-0.003	0.025	0.24	6	-10000	0	6
GSK3B	-0.049	0.1	0.18	3	-0.31	27	30
RELN/VLDLR/DAB1/Fyn	-0.038	0.09	0.14	22	-0.16	171	193
MAP3K11	-0.006	0.013	-10000	0	-0.31	1	1
RELN/VLDLR/DAB1/P13K	-0.047	0.12	0.21	3	-0.21	170	173
CDK5	0.022	0.079	0.24	65	-10000	0	65
MAPT	0.006	0.014	-10000	0	-10000	0	0
neuron migration	-0.054	0.12	0.18	14	-0.26	94	108
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.044	0.084	0.18	1	-0.34	13	14
RELN/VLDLR	-0.016	0.08	0.16	29	-0.16	110	139

×

Ras signaling in the CD4+ TCR pathway

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
ERK1-2/ELK1	-0.005	0.13	0.4	26	-0.29	52	78
MAP3K8	-0.006	0.007	-10000	0	-10000	0	0
FOS	0.006	0.095	0.31	26	-0.35	6	32
PRKCA	-0.004	0.04	0.24	7	-0.31	4	11
PTPN7	-0.004	0.02	-10000	0	-10000	0	0
HRAS	-0.006	0.004	-10000	0	-10000	0	0
PRKCB	0	0.011	0.045	26	-0.018	3	29
NRAS	0.12	0.12	0.24	300	-10000	0	300
RAS family/GTP	0.094	0.085	0.17	281	-10000	0	281
MAPK3	0.002	0.089	0.21	26	-0.45	14	40
MAP2K1	0.022	0.057	0.19	29	-0.29	4	33
ELK1	-0.007	0.014	-10000	0	-10000	0	0
BRAF	0.003	0.04	0.17	14	-0.28	4	18
mol:GTP	0	0.003	0.008	26	-0.006	65	91
MAPK1	0.012	0.055	0.22	12	-0.37	1	13
RAF1	0.003	0.039	0.21	3	-0.28	4	7
KRAS	0.025	0.082	0.24	71	-10000	0	71

×

Thromboxane A2 receptor signaling

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
TGM2	-0.2	0.15	0.25	1	-0.31	367	368
GNB1/GNG2	-0.064	0.065	-10000	0	-0.2	78	78
AKT1	-0.038	0.18	0.36	80	-10000	0	80
EGF	-0.003	0.027	0.24	7	-10000	0	7
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	-0.017	0.04	0.28	1	-10000	0	1
mol:Ca2+	-0.083	0.25	0.43	78	-0.36	63	141
LYN	-0.02	0.045	0.28	1	-0.24	1	2
RhoA/GTP	-0.062	0.053	-10000	0	-0.13	108	108
mol:PGI2	0	0.001	-10000	0	-10000	0	0
SYK	-0.08	0.25	0.44	80	-0.38	65	145
GNG2	-0.004	0.011	0.24	1	-10000	0	1
ARRB2	-0.006	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.033	0.09	-10000	0	-0.29	60	60
G beta5/gamma2	-0.078	0.086	0.14	1	-0.26	77	78
PRKCH	-0.094	0.26	0.45	80	-0.42	65	145
DNM1	-0.006	0.013	-10000	0	-0.31	1	1
TXA2/TP beta/beta Arrestin3	0.015	0.022	-10000	0	-10000	0	0
mol:GTP	0	0.006	0.1	1	-10000	0	1
PTGDR	-0.004	0.004	-10000	0	-10000	0	0
G12 family/GTP	-0.14	0.12	-10000	0	-0.24	308	308
ADRBK1	-0.004	0.004	-10000	0	-10000	0	0
ADRBK2	-0.031	0.086	-10000	0	-0.31	50	50
RhoA/GTP/ROCK1	-0.002	0.015	0.15	1	-0.18	2	3
mol:GDP	0.064	0.19	0.45	33	-0.31	75	108
mol:NADP	-0.005	0.004	-10000	0	-10000	0	0
RAB11A	-0.006	0	-10000	0	-10000	0	0
PRKG1	-0.005	0.011	0.24	1	-10000	0	1
mol:IP3	-0.11	0.28	0.46	78	-0.45	65	143
cell morphogenesis	-0.002	0.015	0.15	1	-0.18	2	3
PLCB2	-0.17	0.33	0.5	72	-0.62	76	148
mol:cGMP	-0.001	0.001	-10000	0	-10000	0	0
BLK	-0.017	0.041	0.21	2	-10000	0	2
mol:PDG2	0	0.001	-10000	0	-10000	0	0
HCK	-0.017	0.041	0.22	2	-10000	0	2
RHOA	-0.007	0.018	-10000	0	-0.31	2	2
PTGIR	-0.006	0.018	-10000	0	-0.31	2	2
PRKCB1	-0.1	0.28	0.46	80	-0.43	76	156
GNAQ	-0.012	0.043	-10000	0	-0.31	12	12
mol:L-citrulline	-0.005	0.004	-10000	0	-10000	0	0
TXA2/TXA2-R family	-0.14	0.33	0.51	79	-0.58	76	155
LCK	-0.017	0.04	0.28	1	-10000	0	1
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.004	0.018	-10000	0	-10000	0	0
TXA2-R family/G12 family/GDP/G beta/gamma	0.001	0.02	-10000	0	-0.43	1	1
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.004	0.018	-10000	0	-10000	0	0
MAPK14	-0.045	0.2	0.38	80	-0.26	1	81
TGM2/GTP	-0.16	0.32	0.49	73	-0.51	87	160
MAPK11	-0.046	0.2	0.38	80	-0.26	2	82
ARHGEF1	-0.046	0.16	0.3	73	-10000	0	73
GNAI2	-0.006	0	-10000	0	-10000	0	0
JNK cascade	-0.091	0.28	0.48	80	-0.42	76	156
RAB11/GDP	-0.001	0.011	-10000	0	-0.14	1	1
ICAM1	-0.045	0.24	0.45	80	-0.38	6	86
cAMP biosynthetic process	-0.13	0.27	0.43	72	-0.42	66	138
Gq family/GTP/EBP50	-0.065	0.11	-10000	0	-0.23	162	162
actin cytoskeleton reorganization	-0.002	0.015	0.15	1	-0.18	2	3
SRC	-0.017	0.04	0.28	1	-10000	0	1
GNB5	-0.008	0.031	-10000	0	-0.31	6	6
GNB1	-0.006	0.013	-10000	0	-0.31	1	1
EGF/EGFR	-0.031	0.057	0.26	1	-0.19	19	20
VCAM1	-0.055	0.25	0.46	80	-0.38	74	154
TP beta/Gq family/GDP/G beta5/gamma2	-0.033	0.09	-10000	0	-0.29	60	60
platelet activation	-0.077	0.24	0.43	80	-0.33	63	143
PGI2/IP	-0.002	0.013	-10000	0	-0.21	2	2
PRKACA	-0.003	0.012	-10000	0	-0.18	2	2
Gq family/GDP/G beta5/gamma2	-0.03	0.083	-10000	0	-0.26	60	60
TXA2/TP beta/beta Arrestin2	0.011	0.028	-10000	0	-0.37	1	1
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.005	0.013	-10000	0	-0.17	1	1
mol:DAG	-0.12	0.29	0.48	73	-0.49	76	149
EGFR	-0.03	0.083	0.24	1	-0.31	46	47
TXA2/TP alpha	-0.18	0.33	0.49	72	-0.54	98	170
Gq family/GTP	-0.019	0.055	0.12	1	-0.17	61	62
YES1	-0.011	0.049	0.17	8	-10000	0	8
GNAI2/GTP	-0.019	0.039	-10000	0	-0.15	1	1
PGD2/DP	-0.002	0.005	-10000	0	-10000	0	0
SLC9A3R1	-0.075	0.13	-10000	0	-0.31	130	130
FYN	-0.03	0.059	0.28	1	-0.23	13	14
mol:NO	-0.005	0.004	-10000	0	-10000	0	0
GNA15	-0.006	0.016	0.24	1	-0.31	1	2
PGK/cGMP	-0.002	0.01	0.15	1	-10000	0	1
RhoA/GDP	-0.002	0.021	-10000	0	-0.25	3	3
TP alpha/TGM2/GDP/G beta/gamma	-0.09	0.061	-10000	0	-0.28	1	1
NOS3	-0.005	0.004	-10000	0	-10000	0	0
RAC1	-0.006	0.013	-10000	0	-0.31	1	1
PRKCA	-0.093	0.26	0.45	80	-0.42	65	145
PRKCB	-0.09	0.26	0.45	80	-0.4	76	156
PRKCE	-0.089	0.26	0.46	80	-0.4	76	156
PRKCD	-0.094	0.27	0.46	80	-0.42	76	156
PRKCG	-0.11	0.28	0.46	80	-0.44	76	156
muscle contraction	-0.13	0.32	0.49	79	-0.54	76	155
PRKCZ	-0.08	0.26	0.45	80	-0.38	65	145
ARR3	-0.006	0	-10000	0	-10000	0	0
TXA2/TP beta	-0.014	0.046	0.27	1	-10000	0	1
PRKCQ	-0.092	0.26	0.45	80	-0.4	77	157
MAPKKK cascade	-0.13	0.31	0.47	79	-0.53	76	155
SELE	-0.054	0.23	0.43	80	-0.32	3	83
TP beta/GNAI2/GDP/G beta/gamma	-0.008	0.015	-10000	0	-10000	0	0
ROCK1	-0.005	0.01	0.24	1	-10000	0	1
GNA14	-0.005	0.015	0.24	2	-10000	0	2
chemotaxis	-0.14	0.35	0.54	79	-0.62	76	155
GNA12	-0.006	0	-10000	0	-10000	0	0
GNA13	-0.006	0.013	-10000	0	-0.31	1	1
GNA11	-0.034	0.088	-10000	0	-0.31	53	53
Rac1/GTP	-0.003	0.011	-10000	0	-0.21	1	1

×

IL4-mediated signaling events

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
BCL2L1	-0.07	0.54	0.91	6	-1.2	47	53
STAT6 (cleaved dimer)	-0.25	0.41	0.53	1	-1.1	85	86
IGHG1	0.025	0.27	0.57	42	-0.94	3	45
IGHG3	-0.079	0.5	0.76	6	-1.2	51	57
AKT1	-0.081	0.34	0.55	3	-0.91	34	37
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.029	0.32	0.5	9	-1	26	35
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.15	0.37	0.6	1	-0.98	45	46
THY1	-0.015	0.59	1	40	-1.3	41	81
MYB	-0.025	0.075	0.24	1	-0.31	37	38
HMGA1	-0.004	0.028	0.24	6	-0.31	1	7
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.019	0.38	0.65	40	-0.95	23	63
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.038	0.37	0.59	10	-1.2	23	33
SP1	0.067	0.11	0.22	183	-10000	0	183
INPP5D	0	0	-10000	0	-10000	0	0
SOCS5	-0.007	0.034	0.24	2	-10000	0	2
STAT6 (dimer)/ETS1	-0.12	0.52	0.7	2	-1.2	62	64
SOCS1	-0.058	0.37	0.62	2	-0.79	51	53
SOCS3	-0.023	0.33	0.61	1	-0.86	20	21
FCER2	-0.013	0.42	0.83	11	-0.89	20	31
PARP14	0.049	0.11	0.24	129	-0.31	3	132
CCL17	-0.07	0.54	0.91	6	-1.2	48	54
GRB2	-0.006	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.012	0.29	0.54	11	-0.74	23	34
T cell proliferation	-0.13	0.57	0.75	1	-1.3	70	71
IL4R/JAK1	-0.14	0.58	0.72	6	-1.4	72	78
EGR2	-0.068	0.54	0.97	8	-1.2	48	56
JAK2	0.02	0.079	0.19	44	-0.35	2	46
JAK3	-0.001	0.012	-10000	0	-10000	0	0
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
JAK1	0.011	0.037	-10000	0	-0.31	2	2
COL1A2	0.096	0.35	0.6	104	-1.2	6	110
CCL26	-0.07	0.54	0.9	7	-1.2	48	55
IL4R	-0.11	0.67	0.91	38	-1.5	68	106
PTPN6	-0.005	0.027	-10000	0	-10000	0	0
IL13RA2	-0.059	0.54	0.93	13	-1.2	47	60
IL13RA1	0.017	0.086	0.19	42	-0.34	7	49
IRF4	0.023	0.17	0.56	1	-10000	0	1
ARG1	0.026	0.23	0.59	6	-0.82	3	9
CBL	-0.026	0.35	0.62	12	-0.89	24	36
GTF3A	0.12	0.12	0.23	293	-10000	0	293
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
IL13RA1/JAK2	0.039	0.12	0.28	49	-0.25	9	58
IRF4/BCL6	0.009	0.14	-10000	0	-10000	0	0
CD40LG	-0.005	0.014	0.24	2	-10000	0	2
MAPK14	-0.026	0.36	0.62	12	-0.89	24	36
mitosis	-0.074	0.33	0.53	4	-0.85	32	36
STAT6	-0.06	0.65	1.1	42	-1.4	50	92
SPI1	-0.007	0.02	0.19	1	-0.31	2	3
RPS6KB1	-0.071	0.32	0.54	4	-0.86	28	32
STAT6 (dimer)	-0.062	0.64	1.1	42	-1.4	50	92
STAT6 (dimer)/PARP14	-0.074	0.54	0.8	10	-1.3	51	61
mast cell activation	-0.005	0.024	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.036	0.36	0.58	10	-1.1	26	36
FRAP1	-0.081	0.34	0.55	3	-0.91	34	37
LTA	-0.07	0.54	0.91	6	-1.2	47	53
FES	-0.006	0	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0.054	0.63	1.4	50	-1.1	42	92
CCL11	-0.068	0.52	0.86	20	-1.2	48	68
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.036	0.36	0.58	9	-1.1	26	35
IL2RG	-0.004	0.089	0.24	30	-0.3	30	60
IL10	-0.07	0.54	0.91	6	-1.2	48	54
IRS1	-0.2	0.15	-10000	0	-0.31	357	357
IRS2	-0.006	0	-10000	0	-10000	0	0
IL4	0.053	0.24	0.63	39	-10000	0	39
IL5	-0.07	0.54	0.91	6	-1.2	48	54
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.027	0.51	0.88	42	-1	47	89
COL1A1	0.22	0.4	0.78	118	-1.5	1	119
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.16	0.59	0.72	1	-1.4	68	69
IL2R gamma/JAK3	-0.001	0.063	0.18	30	-0.2	30	60
TFF3	-0.65	0.6	0.89	4	-1.3	167	171
ALOX15	-0.072	0.54	0.91	6	-1.2	49	55
MYBL1	0.027	0.084	0.24	76	-10000	0	76
T-helper 2 cell differentiation	-0.059	0.49	0.77	11	-1.1	55	66
SHC1	-0.006	0	-10000	0	-10000	0	0
CEBPB	-0.007	0.029	0.22	2	-0.31	4	6
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.037	0.37	0.57	11	-1.2	23	34
mol:PI-3-4-5-P3	-0.081	0.34	0.55	3	-0.91	34	37
PI3K	-0.09	0.36	0.55	3	-0.99	35	38
DOK2	-0.005	0.01	0.24	1	-10000	0	1
ETS1	-0.008	0.05	0.24	10	-10000	0	10
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.011	0.28	0.48	25	-0.72	23	48
ITGB3	-0.14	0.66	1	9	-1.4	83	92
PIGR	-0.099	0.59	1	11	-1.3	63	74
IGHE	-0.048	0.098	-10000	0	-0.25	69	69
MAPKKK cascade	-0.01	0.28	0.46	40	-0.7	23	63
BCL6	-0.013	0.047	-10000	0	-0.31	14	14
OPRM1	-0.07	0.54	0.91	6	-1.2	47	53
RETNLB	-0.07	0.54	0.9	7	-1.2	48	55
SELP	-0.096	0.56	0.92	7	-1.3	57	64
AICDA	-0.079	0.5	0.76	6	-1.2	48	54

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.01	0.033	-10000	0	-0.31	7	7
alphaV beta3 Integrin	-0.026	0.088	0.19	28	-0.22	78	106
PTK2	-0.05	0.11	0.21	7	-0.41	31	38
positive regulation of JNK cascade	-0.028	0.069	-10000	0	-0.29	34	34
CDC42/GDP	-0.022	0.1	-10000	0	-0.39	34	34
Rac1/GDP	-0.022	0.1	-10000	0	-0.39	34	34
RAP1B	-0.004	0.023	0.24	5	-10000	0	5
RAP1A	-0.005	0.01	0.24	1	-10000	0	1
CTNNB1	-0.005	0.015	0.24	2	-10000	0	2
CDC42/GTP	-0.032	0.085	-10000	0	-0.36	34	34
nectin-3/I-afadin	0.003	0.077	0.17	69	-0.21	31	100
RAPGEF1	-0.029	0.11	-10000	0	-0.43	34	34
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.03	0.13	-10000	0	-0.48	34	34
PDGFB-D/PDGFRB	-0.01	0.033	-10000	0	-0.31	7	7
TLN1	-0.11	0.13	-10000	0	-0.26	235	235
Rap1/GTP	-0.035	0.074	-10000	0	-0.32	34	34
IQGAP1	-0.006	0.021	0.24	1	-0.31	2	3
Rap1/GTP/I-afadin	0.001	0.04	0.15	6	-0.16	29	35
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.003	0.077	0.17	69	-0.21	31	100
PVR	-0.006	0	-10000	0	-10000	0	0
Necl-5(dimer)	-0.006	0	-10000	0	-10000	0	0
mol:GDP	-0.027	0.12	-10000	0	-0.48	34	34
MLLT4	-0.021	0.066	-10000	0	-0.31	29	29
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
PI3K	0.007	0.11	0.28	12	-0.17	119	131
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.017	0.046	0.17	1	-0.21	29	30
positive regulation of lamellipodium assembly	-0.03	0.075	-10000	0	-0.31	36	36
PVRL1	-0.005	0.01	0.24	1	-10000	0	1
PVRL3	0.023	0.088	0.24	72	-0.31	5	77
PVRL2	-0.006	0.016	0.24	1	-0.31	1	2
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
CDH1	-0.013	0.045	-10000	0	-0.31	13	13
CLDN1	-0.094	0.14	0.24	1	-0.31	167	168
JAM-A/CLDN1	-0.031	0.1	0.15	51	-0.17	165	216
SRC	-0.032	0.14	-10000	0	-0.53	34	34
ITGB3	-0.041	0.11	0.24	12	-0.31	77	89
nectin-1(dimer)/I-afadin/I-afadin	-0.017	0.046	0.17	1	-0.21	29	30
FARP2	-0.025	0.12	-10000	0	-0.46	34	34
RAC1	-0.006	0.013	-10000	0	-0.31	1	1
CTNNA1	-0.007	0.018	-10000	0	-0.31	2	2
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.017	0.067	0.16	69	-0.18	31	100
nectin-1/I-afadin	-0.017	0.046	0.17	1	-0.21	29	30
nectin-2/I-afadin	-0.017	0.046	0.17	1	-0.21	30	31
RAC1/GTP/IQGAP1/filamentous actin	0.005	0.014	0.15	1	-0.18	3	4
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.017	0.067	0.16	70	-0.18	31	101
CDC42/GTP/IQGAP1/filamentous actin	0.005	0.012	0.15	1	-0.18	2	3
F11R	-0.005	0.01	0.24	1	-10000	0	1
positive regulation of filopodium formation	-0.028	0.069	-10000	0	-0.29	34	34
alphaV/beta3 Integrin/Talin	-0.12	0.14	0.17	13	-0.26	236	249
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.017	0.046	0.17	1	-0.21	30	31
nectin-2(dimer)/I-afadin/I-afadin	-0.017	0.046	0.17	1	-0.21	30	31
PIP5K1C	-0.11	0.14	-10000	0	-0.27	235	235
VAV2	-0.027	0.13	-10000	0	-0.48	36	36
RAP1/GDP	-0.029	0.092	0.19	1	-0.37	34	35
ITGAV	0.001	0.05	0.24	19	-0.31	3	22
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.016	0.068	0.16	70	-0.18	32	102
nectin-3(dimer)/I-afadin/I-afadin	0.003	0.077	0.17	69	-0.21	31	100
Rac1/GTP	-0.033	0.092	-10000	0	-0.37	36	36
PTPRM	-0.12	0.16	-10000	0	-0.29	244	244
E-cadherin/beta catenin/alpha catenin	0.001	0.046	-10000	0	-0.16	39	39
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	-0.006	0	-10000	0	-10000	0	0

×

FAS signaling pathway (CD95)

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
SPTAN1	0.023	0.064	0.16	92	-0.16	6	98
RFC1	0.027	0.065	0.16	100	-0.16	1	101
PRKDC	0.051	0.089	0.18	167	-0.16	1	168
RIPK1	-0.006	0.005	-10000	0	-10000	0	0
CASP7	0.002	0.024	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1	0.018	0.081	0.26	2	-0.19	16	18
MAP2K4	-0.002	0.063	0.29	10	-0.28	8	18
mol:ceramide	-0.007	0.052	0.24	10	-10000	0	10
GSN	0.005	0.077	0.16	77	-0.16	54	131
FASLG/FAS/FADD/FAF1/Caspase 8	0.014	0.073	0.25	2	-0.31	1	3
FAS	-0.016	0.058	0.24	1	-0.31	21	22
BID	-0.007	0.008	0.17	1	-10000	0	1
MAP3K1	0.006	0.048	0.21	10	-10000	0	10
MAP3K7	-0.003	0.026	0.24	6	-10000	0	6
RB1	0.029	0.069	0.17	90	-0.16	2	92
CFLAR	-0.006	0.005	-10000	0	-10000	0	0
HGF/MET	-0.015	0.1	0.16	74	-0.19	124	198
ARHGDIB	0.014	0.074	0.16	86	-0.16	33	119
FADD	-0.005	0.007	-10000	0	-10000	0	0
actin filament polymerization	-0.005	0.077	0.16	54	-0.16	77	131
NFKB1	-0.004	0.088	0.28	10	-0.67	7	17
MAPK8	-0.004	0.081	0.35	10	-0.44	9	19
DFFA	0.024	0.062	0.16	93	-0.16	1	94
DNA fragmentation during apoptosis	0.024	0.062	0.16	93	-0.15	1	94
FAS/FADD/MET	0.014	0.068	0.16	58	-0.19	29	87
CFLAR/RIP1	-0.007	0.008	-10000	0	-10000	0	0
FAIM3	-0.006	0.002	-10000	0	-10000	0	0
FAF1	-0.003	0.027	0.24	6	-10000	0	6
PARP1	0.037	0.075	0.17	132	-0.16	1	133
DFFB	0.024	0.062	0.16	93	-0.16	1	94
CHUK	-0.002	0.082	0.24	10	-0.62	7	17
FASLG	-0.005	0.009	-10000	0	-10000	0	0
FAS/FADD	-0.013	0.041	0.17	1	-0.21	21	22
HGF	-0.004	0.021	0.24	4	-10000	0	4
LMNA	0.055	0.087	0.27	39	-10000	0	39
CASP6	0.065	0.098	0.22	98	-0.16	1	99
CASP10	-0.004	0.022	0.24	4	-10000	0	4
CASP3	0.032	0.074	0.19	93	-0.17	1	94
PTPN13	-0.057	0.14	0.24	32	-0.31	123	155
CASP8	-0.006	0.003	-10000	0	-10000	0	0
IL6	-0.013	0.16	0.52	10	-0.99	11	21
MET	0.014	0.089	0.24	59	-0.31	12	71
ICAD/CAD	0.02	0.055	0.2	5	-10000	0	5
FASLG/FAS/FADD/FAF1/Caspase 10	-0.007	0.052	0.24	10	-10000	0	10
activation of caspase activity by cytochrome c	-0.007	0.008	0.17	1	-10000	0	1
PAK2	0.025	0.063	0.16	94	-0.16	1	95
BCL2	-0.055	0.11	0.24	1	-0.31	93	94

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.011	0.054	-10000	0	-0.15	75	75
ER alpha/Gai/GDP/Gbeta gamma	-0.02	0.11	-10000	0	-0.29	61	61
AKT1	-0.096	0.24	-10000	0	-0.67	75	75
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.091	0.25	-10000	0	-0.68	75	75
mol:Ca2+	-0.032	0.072	-10000	0	-0.33	16	16
IGF1R	-0.07	0.12	-10000	0	-0.31	121	121
E2/ER alpha (dimer)/Striatin	-0.017	0.062	0.15	2	-0.18	75	77
SHC1	-0.006	0	-10000	0	-10000	0	0
apoptosis	0.091	0.23	0.65	75	-10000	0	75
RhoA/GTP	-0.012	0.028	-10000	0	-0.14	24	24
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.039	0.1	-10000	0	-0.3	74	74
regulation of stress fiber formation	-0.038	0.075	0.23	2	-0.2	39	41
E2/ERA-ERB (dimer)	-0.018	0.061	-10000	0	-0.18	75	75
KRAS	0.025	0.082	0.24	71	-10000	0	71
G13/GTP	-0.016	0.055	-10000	0	-0.16	76	76
pseudopodium formation	0.038	0.075	0.2	39	-0.23	2	41
E2/ER alpha (dimer)/PELP1	-0.018	0.061	-10000	0	-0.18	75	75
GRB2	-0.006	0	-10000	0	-10000	0	0
GNG2	-0.005	0.01	0.24	1	-10000	0	1
GNAO1	-0.004	0.028	0.24	6	-0.31	1	7
HRAS	-0.006	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.046	0.14	-10000	0	-0.39	74	74
E2/ER beta (dimer)	-0.003	0	-10000	0	-10000	0	0
mol:GDP	-0.028	0.071	-10000	0	-0.22	68	68
mol:NADP	-0.046	0.14	-10000	0	-0.39	74	74
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
mol:IP3	-0.033	0.074	-10000	0	-0.34	16	16
IGF-1R heterotetramer	-0.07	0.12	-10000	0	-0.31	121	121
PLCB1	-0.032	0.076	-10000	0	-0.35	16	16
PLCB2	-0.035	0.074	-10000	0	-0.35	16	16
IGF1	-0.016	0.06	0.24	3	-0.31	21	24
mol:L-citrulline	-0.046	0.14	-10000	0	-0.39	74	74
RHOA	-0.007	0.018	-10000	0	-0.31	2	2
Gai/GDP	0.019	0.055	-10000	0	-0.65	1	1
JNK cascade	-0.003	0	-10000	0	-10000	0	0
BCAR1	-0.006	0.013	-10000	0	-0.31	1	1
ESR2	-0.006	0	-10000	0	-10000	0	0
GNAQ	-0.012	0.043	-10000	0	-0.31	12	12
ESR1	-0.046	0.1	-10000	0	-0.31	75	75
Gq family/GDP/Gbeta gamma	-0.033	0.1	-10000	0	-0.33	55	55
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.016	0.075	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.039	0.1	-10000	0	-0.3	74	74
GNAZ	-0.008	0.025	-10000	0	-0.31	4	4
E2/ER alpha (dimer)	-0.031	0.069	-10000	0	-0.21	75	75
STRN	-0.005	0.015	0.24	2	-10000	0	2
GNAL	-0.006	0	-10000	0	-10000	0	0
PELP1	-0.006	0	-10000	0	-10000	0	0
MAPK11	-0.005	0	-10000	0	-10000	0	0
GNAI2	-0.006	0	-10000	0	-10000	0	0
GNAI3	0.036	0.093	0.24	96	-10000	0	96
GNAI1	-0.005	0.041	0.24	8	-0.31	5	13
HBEGF	-0.015	0.1	-10000	0	-0.28	46	46
cAMP biosynthetic process	-0.024	0.045	-10000	0	-0.14	75	75
SRC	-0.021	0.1	-10000	0	-0.28	61	61
PI3K	-0.015	0.12	0.17	98	-0.21	107	205
GNB1	-0.006	0.013	-10000	0	-0.31	1	1
G13/GDP/Gbeta gamma	-0.028	0.062	-10000	0	-0.26	23	23
SOS1	0.005	0.05	0.24	24	-10000	0	24
IGF-1R heterotetramer/IGF1	-0.061	0.099	-10000	0	-0.28	75	75
Gs family/GTP	-0.024	0.046	-10000	0	-0.14	75	75
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.1	0.087	0.17	327	-10000	0	327
vasodilation	-0.044	0.14	-10000	0	-0.38	74	74
mol:DAG	-0.033	0.074	-10000	0	-0.34	16	16
Gs family/GDP/Gbeta gamma	-0.028	0.063	-10000	0	-0.19	68	68
MSN	0.039	0.078	0.2	39	-0.24	2	41
Gq family/GTP	-0.034	0.077	-10000	0	-0.37	16	16
mol:PI-3-4-5-P3	-0.088	0.24	-10000	0	-0.66	75	75
NRAS	0.12	0.12	0.24	300	-10000	0	300
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.044	0.14	0.38	74	-10000	0	74
GRB2/SOS1	0.001	0.036	0.17	24	-10000	0	24
RhoA/GDP	-0.029	0.069	-10000	0	-0.21	68	68
NOS3	-0.048	0.15	-10000	0	-0.41	74	74
GNA11	-0.034	0.088	-10000	0	-0.31	53	53
MAPKKK cascade	-0.051	0.17	0.2	1	-0.48	75	76
E2/ER alpha (dimer)/PELP1/Src	-0.03	0.11	-10000	0	-0.3	74	74
ruffle organization	0.038	0.075	0.2	39	-0.23	2	41
ROCK2	0.044	0.079	0.21	40	-10000	0	40
GNA14	-0.005	0.015	0.24	2	-10000	0	2
GNA15	-0.006	0.016	0.24	1	-0.31	1	2
GNA13	-0.006	0.013	-10000	0	-0.31	1	1
MMP9	-0.003	0.1	0.2	14	-0.27	48	62
MMP2	-0.031	0.11	0.19	2	-0.28	58	60

×

Signaling events mediated by the Hedgehog family

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
TGFB2	0.044	0.2	0.46	90	-0.5	17	107
IHH	0.007	0.055	0.19	1	-0.14	8	9
SHH Np/Cholesterol/GAS1	-0.03	0.056	0.13	1	-0.16	86	87
LRPAP1	-0.006	0.025	0.24	3	-0.31	2	5
dorsoventral neural tube patterning	0.03	0.056	0.16	86	-0.13	1	87
SMO/beta Arrestin2	0.016	0.11	-10000	0	-0.44	8	8
SMO	0.02	0.12	-10000	0	-0.46	8	8
AKT1	-0.022	0.14	0.24	24	-0.52	7	31
ARRB2	-0.006	0	-10000	0	-10000	0	0
BOC	-0.036	0.091	-10000	0	-0.31	57	57
ADRBK1	-0.006	0	-10000	0	-10000	0	0
heart looping	0.02	0.12	-10000	0	-0.46	8	8
STIL	0.12	0.12	0.32	92	-10000	0	92
DHH N/PTCH2	-0.007	0	-10000	0	-10000	0	0
DHH N/PTCH1	-0.02	0.056	-10000	0	-0.28	25	25
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
DHH	-0.006	0	-10000	0	-10000	0	0
PTHLH	0.039	0.19	0.41	90	-0.46	25	115
determination of left/right symmetry	0.02	0.12	-10000	0	-0.46	8	8
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
skeletal system development	0.04	0.18	0.41	90	-0.46	25	115
IHH N/Hhip	0.005	0.039	0.2	4	-10000	0	4
DHH N/Hhip	-0.006	0.015	0.17	4	-10000	0	4
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	0.02	0.12	-10000	0	-0.46	8	8
pancreas development	-0.004	0.021	0.24	4	-10000	0	4
HHAT	-0.01	0.033	-10000	0	-0.31	7	7
PI3K	-0.015	0.12	0.17	98	-0.21	107	205
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.049	0.11	-10000	0	-0.31	81	81
somite specification	0.02	0.12	-10000	0	-0.46	8	8
SHH Np/Cholesterol/PTCH1	0.014	0.1	0.22	89	-0.32	8	97
SHH Np/Cholesterol/PTCH2	-0.009	0.018	0.13	1	-0.16	7	8
SHH Np/Cholesterol/Megalin	0.03	0.07	0.15	139	-0.16	5	144
SHH	-0.009	0.024	0.2	1	-0.21	7	8
catabolic process	0.026	0.13	0.3	90	-0.31	25	115
SMO/Vitamin D3	0.014	0.11	0.23	89	-0.41	8	97
SHH Np/Cholesterol/Hhip	-0.008	0.022	0.15	5	-0.16	7	12
LRP2	0.056	0.11	0.24	141	-10000	0	141
receptor-mediated endocytosis	0.034	0.11	0.3	17	-0.43	8	25
SHH Np/Cholesterol/BOC	-0.024	0.049	0.13	1	-0.16	63	64
SHH Np/Cholesterol/CDO	-0.007	0.026	0.15	8	-0.16	9	17
mesenchymal cell differentiation	0.008	0.022	0.16	7	-0.14	5	12
mol:Vitamin D3	0.016	0.11	0.23	89	-0.32	8	97
IHH N/PTCH2	0.003	0.035	-10000	0	-10000	0	0
CDON	-0.004	0.033	0.24	7	-0.31	2	9
IHH N/PTCH1	0.024	0.13	0.28	90	-0.31	25	115
Megalin/LRPAP1	0.037	0.078	0.17	144	-0.21	2	146
PTCH2	-0.006	0	-10000	0	-10000	0	0
SHH Np/Cholesterol	-0.007	0.017	-10000	0	-0.16	7	7
PTCH1	0.027	0.14	0.3	90	-0.31	25	115
HHIP	-0.004	0.021	0.24	4	-10000	0	4

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.023	0.073	0.16	33	-0.18	74	107
alphaM/beta2 Integrin/GPIbA	-0.01	0.021	0.16	4	-0.18	4	8
alphaM/beta2 Integrin/proMMP-9	0.014	0.062	0.16	85	-0.18	4	89
PLAUR	0	0.037	0.24	13	-10000	0	13
HMGB1	-0.006	0.01	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.01	0.022	0.16	4	-0.18	5	9
AGER	-0.006	0.01	-10000	0	-10000	0	0
RAP1A	-0.005	0.01	0.24	1	-10000	0	1
SELPLG	-0.011	0.038	-10000	0	-0.31	9	9
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.015	0.028	0.15	4	-0.18	9	13
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	0.034	0.091	0.24	92	-10000	0	92
CYR61	-0.008	0.066	0.24	15	-0.31	17	32
TLN1	-0.006	0.013	-10000	0	-0.31	1	1
Rap1/GTP	-0.062	0.072	0.12	2	-0.27	20	22
RHOA	-0.007	0.018	-10000	0	-0.31	2	2
P-selectin oligomer	-0.018	0.062	0.24	1	-0.31	24	25
MYH2	-0.058	0.14	0.19	53	-0.34	22	75
MST1R	-0.003	0.027	0.24	7	-10000	0	7
leukocyte activation during inflammatory response	-0.01	0.018	0.13	5	-0.15	4	9
APOB	-0.005	0.01	0.24	1	-10000	0	1
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	-0.03	0.12	0.24	32	-0.31	71	103
JAM3	-0.005	0.015	0.24	2	-10000	0	2
GP1BA	-0.006	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/CTGF	-0.049	0.076	0.16	4	-0.18	131	135
alphaM/beta2 Integrin	-0.039	0.12	0.18	53	-0.31	21	74
JAM3 homodimer	-0.005	0.015	0.24	2	-10000	0	2
ICAM2	-0.008	0.028	-10000	0	-0.31	5	5
ICAM1	0.024	0.089	0.24	75	-0.31	5	80
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.038	0.12	0.18	53	-0.3	21	74
cell adhesion	-0.01	0.021	0.15	4	-0.18	4	8
NFKB1	-0.014	0.068	0.36	11	-0.31	9	20
THY1	0.072	0.12	0.24	179	-0.31	1	180
RhoA/GDP	-0.004	0.012	-10000	0	-0.21	2	2
Lipoprotein(a)	0.006	0.006	0.15	1	-10000	0	1
alphaM/beta2 Integrin/LRP/tPA	-0.025	0.08	-10000	0	-0.17	123	123
IL6	-0.016	0.1	0.48	11	-0.57	9	20
ITGB2	-0.008	0.029	0.24	1	-0.31	4	5
elevation of cytosolic calcium ion concentration	0.037	0.078	0.15	172	-10000	0	172
alphaM/beta2 Integrin/JAM2/JAM3	-0.044	0.084	0.15	4	-0.16	183	187
JAM2	-0.1	0.14	0.24	1	-0.31	182	183
alphaM/beta2 Integrin/ICAM1	0.03	0.056	0.25	8	-10000	0	8
alphaM/beta2 Integrin/uPA/Plg	0.047	0.075	0.29	3	-0.16	14	17
RhoA/GTP	-0.059	0.15	0.2	53	-0.36	22	75
positive regulation of phagocytosis	-0.051	0.063	0.34	1	-0.24	17	18
Ron/MSP	-0.004	0.021	0.17	8	-10000	0	8
alphaM/beta2 Integrin/uPAR/uPA	0.052	0.072	0.29	6	-0.16	4	10
alphaM/beta2 Integrin/uPAR	-0.008	0.026	0.16	9	-0.18	4	13
PLAU	0.072	0.12	0.24	179	-10000	0	179
PLAT	-0.065	0.13	0.24	7	-0.31	117	124
actin filament polymerization	-0.055	0.14	0.19	53	-0.33	22	75
MST1	-0.005	0.01	0.24	1	-10000	0	1
alphaM/beta2 Integrin/lipoprotein(a)	0.01	0.022	-10000	0	-0.15	4	4
TNF	-0.014	0.066	0.36	11	-10000	0	11
RAP1B	-0.004	0.023	0.24	5	-10000	0	5
alphaM/beta2 Integrin/uPA	0.038	0.078	0.16	168	-0.18	4	172
fibrinolysis	0.032	0.08	0.15	167	-0.16	14	181
HCK	-0.005	0.01	0.24	1	-10000	0	1
dendritic cell antigen processing and presentation	-0.038	0.12	0.18	53	-0.3	21	74
VTN	-0.006	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/CYR61	-0.011	0.043	0.16	16	-0.18	21	37
LPA	-0.006	0	-10000	0	-10000	0	0
LRP1	-0.01	0.036	-10000	0	-0.31	8	8
cell migration	-0.004	0.08	0.25	4	-0.16	65	69
FN1	0.075	0.13	0.24	200	-0.31	12	212
alphaM/beta2 Integrin/Thy1	0.039	0.078	0.16	170	-0.18	3	173
MPO	-0.006	0	-10000	0	-10000	0	0
KNG1	-0.005	0.01	0.24	1	-10000	0	1
RAP1/GDP	0.007	0.015	0.15	6	-10000	0	6
ROCK1	-0.057	0.14	0.19	53	-0.34	22	75
ELA2	-0.006	0	-10000	0	-10000	0	0
PLG	-0.013	0.047	-10000	0	-0.31	14	14
CTGF	-0.075	0.13	-10000	0	-0.31	131	131
alphaM/beta2 Integrin/Hck	-0.01	0.02	0.16	3	-0.18	4	7
ITGAM	-0.005	0.021	0.24	3	-10000	0	3
alphaM/beta2 Integrin/P-Selectin/PSGL1	0.001	0.051	0.29	1	-0.18	34	35
HP	-0.14	0.19	0.24	54	-0.31	300	354
leukocyte adhesion	-0.02	0.1	0.24	2	-0.3	1	3
SELP	-0.018	0.062	0.24	1	-0.31	24	25

×

IL23-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
CCL2	0.13	0.45	1	53	-1.2	17	70
IL23A	0.13	0.37	0.98	40	-10000	0	40
NF kappa B1 p50/RelA/I kappa B alpha	-0.065	0.16	-10000	0	-0.8	13	13
positive regulation of T cell mediated cytotoxicity	0.16	0.43	1	63	-0.84	13	76
ITGA3	0.066	0.46	0.96	29	-1.1	36	65
IL17F	0.063	0.27	0.65	49	-0.62	5	54
IL12B	0.047	0.099	0.28	63	-10000	0	63
STAT1 (dimer)	0.2	0.38	0.87	69	-0.82	9	78
CD4	0.14	0.38	0.99	40	-1.3	1	41
IL23	0.11	0.34	0.84	40	-0.79	2	42
IL23R	0.093	0.21	0.77	27	-10000	0	27
IL1B	0.14	0.39	1	40	-10000	0	40
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	0.13	0.36	0.93	40	-10000	0	40
TYK2	0.028	0.065	0.23	27	-10000	0	27
STAT4	-0.004	0.018	0.24	3	-10000	0	3
STAT3	-0.012	0.04	-10000	0	-0.31	10	10
IL18RAP	-0.004	0.014	-10000	0	-10000	0	0
IL12RB1	0.028	0.065	0.23	27	-10000	0	27
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
IL12Rbeta1/TYK2	0.031	0.072	0.24	29	-10000	0	29
IL23R/JAK2	0.1	0.21	0.57	64	-10000	0	64
positive regulation of chronic inflammatory response	0.16	0.43	1	63	-0.84	13	76
natural killer cell activation	-0.008	0.018	-10000	0	-0.062	33	33
JAK2	0.047	0.1	0.28	65	-0.33	2	67
PIK3R1	-0.076	0.13	-10000	0	-0.31	131	131
NFKB1	-0.003	0.037	-10000	0	-0.31	7	7
RELA	0.001	0.018	-10000	0	-0.32	1	1
positive regulation of dendritic cell antigen processing and presentation	0.11	0.33	0.83	40	-10000	0	40
ALOX12B	0.13	0.36	0.93	40	-10000	0	40
CXCL1	0.13	0.41	0.98	46	-1.2	9	55
T cell proliferation	0.16	0.43	1	63	-0.84	13	76
NFKBIA	-0.006	0.048	-10000	0	-0.31	13	13
IL17A	0.079	0.26	0.6	54	-0.54	1	55
PI3K	-0.04	0.21	0.5	23	-0.81	14	37
IFNG	0.031	0.068	0.26	37	-10000	0	37
STAT3 (dimer)	-0.048	0.2	0.45	19	-0.8	14	33
IL18R1	-0.004	0.017	0.24	1	-10000	0	1
IL23/IL23R/JAK2/TYK2/SOCS3	0.12	0.3	0.74	63	-0.69	1	64
IL18/IL18R	0.035	0.075	0.19	77	-10000	0	77
macrophage activation	-0.002	0.015	0.057	18	-10000	0	18
TNF	0.14	0.37	0.98	40	-10000	0	40
STAT3/STAT4	-0.062	0.16	0.47	1	-0.8	14	15
STAT4 (dimer)	0.11	0.34	0.87	27	-0.82	13	40
IL18	0.043	0.098	0.24	108	-10000	0	108
IL19	0.13	0.36	0.94	40	-10000	0	40
STAT5A (dimer)	0.11	0.34	0.87	27	-0.82	13	40
STAT1	0.13	0.12	0.24	314	-10000	0	314
SOCS3	-0.006	0.023	0.24	2	-0.31	2	4
CXCL9	0.18	0.42	1.1	54	-10000	0	54
MPO	0.13	0.36	0.94	38	-10000	0	38
positive regulation of humoral immune response	0.16	0.43	1	63	-0.84	13	76
IL23/IL23R/JAK2/TYK2	0.16	0.43	1	63	-0.86	13	76
IL6	0.12	0.39	1	31	-1.2	8	39
STAT5A	-0.01	0.036	-10000	0	-0.31	8	8
IL2	-0.003	0.035	0.14	26	-10000	0	26
positive regulation of tyrosine phosphorylation of STAT protein	-0.008	0.018	-10000	0	-0.062	33	33
CD3E	0.13	0.38	0.96	41	-1.1	4	45
keratinocyte proliferation	0.16	0.43	1	63	-0.84	13	76
NOS2	0.13	0.36	0.84	63	-0.77	13	76

×

p75(NTR)-mediated signaling

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
Sortilin/TRAF6	-0.004	0.021	0.17	8	-10000	0	8
Necdin/E2F1	-0.12	0.1	-10000	0	-0.21	321	321
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.011	0.02	0.14	7	-0.15	4	11
NGF (dimer)/p75(NTR)/BEX1	-0.046	0.095	0.15	28	-0.18	185	213
NT-4/5 (dimer)/p75(NTR)	-0.003	0.007	0.17	1	-10000	0	1
IKBKB	-0.005	0.015	0.24	2	-10000	0	2
AKT1	-0.013	0.081	0.12	99	-0.15	106	205
IKBKG	-0.006	0	-10000	0	-10000	0	0
BDNF	-0.006	0	-10000	0	-10000	0	0
MGDIs/NGR/p75(NTR)/LINGO1	0.01	0.012	0.16	4	-10000	0	4
FURIN	-0.011	0.038	-10000	0	-0.31	9	9
proBDNF (dimer)/p75(NTR)/Sortilin	0.011	0.016	0.16	7	-10000	0	7
LINGO1	-0.004	0.023	0.24	5	-10000	0	5
Sortilin/TRAF6/NRIF	-0.033	0.044	-10000	0	-0.14	78	78
proBDNF (dimer)	-0.006	0	-10000	0	-10000	0	0
NTRK1	-0.006	0	-10000	0	-10000	0	0
RTN4R	-0.005	0.01	0.24	1	-10000	0	1
neuron apoptosis	-0.008	0.076	0.2	1	-10000	0	1
IRAK1	-0.004	0.018	0.24	3	-10000	0	3
SHC1	-0.005	0.007	0.15	1	-10000	0	1
ARHGDIA	-0.049	0.11	-10000	0	-0.31	81	81
RhoA/GTP	-0.004	0.012	-10000	0	-0.21	2	2
Gamma Secretase	-0.01	0.059	-10000	0	-0.15	79	79
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.005	0.032	0.15	6	-0.16	17	23
MAGEH1	-0.015	0.053	-10000	0	-0.31	18	18
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.084	0.083	0.15	1	-0.16	315	316
Mammalian IAPs/DIABLO	0.066	0.12	0.18	240	-0.16	53	293
proNGF (dimer)	0	0	-10000	0	-10000	0	0
MAGED1	-0.007	0.024	0.24	1	-0.31	3	4
APP	-0.011	0.038	-10000	0	-0.31	9	9
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
ZNF274	-0.006	0	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.027	0.051	0.12	1	-0.15	82	83
NGF	0	0	-10000	0	-10000	0	0
cell cycle arrest	0.025	0.047	0.18	6	-10000	0	6
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.033	0.053	0.22	2	-10000	0	2
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.007	0.011	0.15	3	-10000	0	3
NCSTN	-0.005	0.01	0.24	1	-10000	0	1
mol:GTP	0.009	0.02	0.15	11	-10000	0	11
PSENEN	-0.016	0.054	-10000	0	-0.31	19	19
mol:ceramide	-0.007	0.023	0.13	7	-0.16	7	14
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.071	0.068	0.18	100	-10000	0	100
p75(NTR)/beta APP	-0.01	0.027	0.17	1	-0.21	9	10
BEX1	-0.092	0.16	0.24	27	-0.31	185	212
mol:GDP	-0.002	0.006	0.15	1	-10000	0	1
NGF (dimer)	-0.052	0.093	0.15	21	-0.16	216	237
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.012	0.062	0.15	4	-0.16	81	85
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
RAC1/GTP	0.005	0.008	0.14	1	-0.15	1	2
MYD88	-0.006	0	-10000	0	-10000	0	0
CHUK	0.002	0.043	0.24	18	-10000	0	18
NGF (dimer)/p75(NTR)/PKA	0.009	0.02	0.15	11	-10000	0	11
RHOB	-0.012	0.042	-10000	0	-0.31	11	11
RHOA	-0.007	0.018	-10000	0	-0.31	2	2
MAGE-G1/E2F1	-0.008	0.012	-10000	0	-0.21	2	2
NT3 (dimer)	0.029	0.086	0.24	80	-10000	0	80
TP53	-0.031	0.051	0.14	1	-10000	0	1
PRDM4	-0.006	0.015	0.13	7	-10000	0	7
BDNF (dimer)	-0.046	0.094	0.15	28	-0.16	209	237
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
SORT1	-0.003	0.025	0.24	6	-10000	0	6
activation of caspase activity	0.01	0.019	0.13	7	-0.15	4	11
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.011	0.017	0.15	9	-10000	0	9
RHOC	-0.006	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
MAPK10	-0.017	0.036	-10000	0	-10000	0	0
DIABLO	0.077	0.12	0.24	190	-10000	0	190
SMPD2	-0.007	0.023	0.13	7	-0.16	7	14
APH1B	-0.038	0.093	-10000	0	-0.31	61	61
APH1A	-0.005	0.01	0.24	1	-10000	0	1
proNGF (dimer)/p75(NTR)/Sortilin	0.008	0.016	0.15	7	-10000	0	7
PSEN1	-0.005	0.01	0.24	1	-10000	0	1
APAF-1/Pro-Caspase 9	-0.001	0.031	0.17	18	-10000	0	18
NT3 (dimer)/p75(NTR)	0.018	0.062	0.17	81	-10000	0	81
MAPK8	-0.012	0.029	-10000	0	-10000	0	0
MAPK9	-0.013	0.028	-10000	0	-10000	0	0
APAF1	0.002	0.042	0.24	17	-10000	0	17
NTF3	0.029	0.086	0.24	80	-10000	0	80
NTF4	0	0	-10000	0	-10000	0	0
NDN	-0.18	0.15	-10000	0	-0.31	321	321
RAC1/GDP	-0.004	0.009	-10000	0	-0.21	1	1
RhoA-B-C/GDP	-0.013	0.02	-10000	0	-0.14	13	13
p75 CTF/Sortilin/TRAF6/NRIF	0.038	0.057	0.15	108	-10000	0	108
RhoA-B-C/GTP	0.009	0.02	0.15	11	-10000	0	11
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.015	0.016	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.013	0.017	0.15	9	-10000	0	9
PRKACB	-0.001	0.033	0.24	10	-10000	0	10
proBDNF (dimer)/p75 ECD	0.025	0.068	0.17	102	-10000	0	102
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.047	0.12	0.24	16	-0.31	90	106
BIRC2	0.059	0.11	0.24	149	-10000	0	149
neuron projection morphogenesis	-0.025	0.07	0.15	6	-0.21	10	16
BAD	-0.015	0.03	-10000	0	-10000	0	0
RIPK2	0.073	0.12	0.24	180	-10000	0	180
NGFR	-0.005	0.01	0.24	1	-10000	0	1
CYCS	-0.007	0.022	0.13	12	-0.15	3	15
ADAM17	0.039	0.095	0.24	102	-10000	0	102
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.053	0.066	0.15	182	-10000	0	182
BCL2L11	-0.015	0.03	-10000	0	-10000	0	0
BDNF (dimer)/p75(NTR)	-0.007	0.007	0.17	1	-10000	0	1
PI3K	0	0.093	0.15	99	-0.16	107	206
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.009	0.018	0.15	7	-0.16	2	9
NDNL2	-0.007	0.018	-10000	0	-0.31	2	2
YWHAE	-0.006	0.013	-10000	0	-0.31	1	1
PRKCI	0.1	0.12	0.24	255	-10000	0	255
NGF (dimer)/p75(NTR)	-0.003	0.007	0.17	1	-10000	0	1
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.009	0.021	0.15	8	-0.16	3	11
TRAF6	-0.005	0.015	0.24	2	-10000	0	2
RAC1	-0.006	0.013	-10000	0	-0.31	1	1
PRKCZ	-0.006	0	-10000	0	-10000	0	0
PLG	-0.013	0.047	-10000	0	-0.31	14	14
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	0.031	0.063	0.13	154	-10000	0	154
SQSTM1	-0.006	0	-10000	0	-10000	0	0
NGFRAP1	-0.007	0.022	-10000	0	-0.31	3	3
CASP3	-0.014	0.029	-10000	0	-10000	0	0
E2F1	-0.006	0	-10000	0	-10000	0	0
CASP9	-0.005	0.01	0.24	1	-10000	0	1
IKK complex	-0.003	0.012	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.003	0	-10000	0	-10000	0	0
MMP7	-0.1	0.16	0.24	21	-0.31	200	221
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.012	0.016	0.14	9	-10000	0	9
MMP3	-0.001	0.033	0.24	10	-10000	0	10
APAF-1/Caspase 9	-0.02	0.037	-10000	0	-10000	0	0

×

Effects of Botulinum toxin

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
STX1A	-0.003	0	-10000	0	-10000	0	0
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	-0.007	0	-10000	0	-10000	0	0
STXBP1	-0.038	0.093	-10000	0	-0.31	61	61
ACh/CHRNA1	-0.04	0.049	0.14	26	-10000	0	26
RAB3GAP2/RIMS1/UNC13B	0.011	0.017	0.16	8	-10000	0	8
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	-10000	0	-10000	0	0
mol:ACh	-0.062	0.038	0.069	1	-0.085	412	413
RAB3GAP2	-0.002	0.029	0.24	8	-10000	0	8
STX1A/SNAP25/VAMP2	-0.11	0.07	0.1	1	-0.25	55	56
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	-0.04	0.049	0.14	26	-10000	0	26
UNC13B	-0.006	0	-10000	0	-10000	0	0
CHRNA1	0.006	0.052	0.24	26	-10000	0	26
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	-0.041	0.048	0.14	24	-10000	0	24
SNAP25	0.001	0.016	0.14	8	-10000	0	8
VAMP2	-0.15	0.087	-10000	0	-0.2	419	419
SYT1	0.005	0.05	0.24	24	-10000	0	24
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	-0.024	0.052	-10000	0	-0.18	61	61
STX1A/SNAP25 fragment 1/VAMP2	-0.11	0.07	0.1	1	-0.25	55	56

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0	0.12	0.24	63	-0.31	40	103
positive regulation of NF-kappaB transcription factor activity	-0.001	0.08	0.17	64	-0.21	40	104
MAP2K4	-0.01	0.068	-10000	0	-0.36	2	2
IKBKB	-0.005	0.015	0.24	2	-10000	0	2
TNFRSF10B	-0.005	0.01	0.24	1	-10000	0	1
TNFRSF10A	-0.005	0.015	0.24	2	-10000	0	2
SMPD1	-0.001	0.049	-10000	0	-10000	0	0
IKBKG	-0.006	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	-0.005	0.01	0.24	1	-10000	0	1
TRAIL/TRAILR2	-0.001	0.08	0.17	64	-0.21	40	104
TRAIL/TRAILR3	-0.08	0.13	0.17	47	-0.23	226	273
TRAIL/TRAILR1	-0.001	0.081	0.17	65	-0.21	40	105
TRAIL/TRAILR4	-0.001	0.08	0.17	64	-0.21	40	104
TRAIL/TRAILR1/DAP3/GTP	0.014	0.066	0.15	72	-0.16	40	112
IKK complex	-0.007	0.036	0.19	3	-10000	0	3
RIPK1	-0.006	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	-0.001	0.019	0.17	7	-10000	0	7
MAPK3	-0.004	0.091	0.2	61	-0.21	52	113
MAP3K1	-0.007	0.07	-10000	0	-0.25	8	8
TRAILR4 (trimer)	-0.005	0.01	0.24	1	-10000	0	1
TRADD	-0.01	0.036	-10000	0	-0.31	8	8
TRAILR1 (trimer)	-0.005	0.015	0.24	2	-10000	0	2
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.006	0.066	-10000	0	-0.36	1	1
CFLAR	-0.006	0	-10000	0	-10000	0	0
MAPK1	0.001	0.088	0.2	64	-0.21	41	105
TRAIL/TRAILR1/FADD/TRADD/RIP	0.014	0.066	-10000	0	-0.29	1	1
mol:ceramide	-0.001	0.049	-10000	0	-10000	0	0
FADD	-0.006	0	-10000	0	-10000	0	0
MAPK8	-0.011	0.065	-10000	0	-0.29	2	2
TRAF2	-0.006	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	-0.12	0.15	0.24	1	-0.31	224	225
CHUK	0.002	0.043	0.24	18	-10000	0	18
TRAIL/TRAILR1/FADD	0.013	0.07	0.16	65	-0.18	40	105
DAP3	-0.003	0.027	0.24	7	-10000	0	7
CASP10	-0.004	0.071	-10000	0	-0.2	40	40
JNK cascade	-0.001	0.08	0.17	64	-0.21	40	104
TRAIL (trimer)	0	0.12	0.24	63	-0.31	40	103
TNFRSF10C	-0.12	0.15	0.24	1	-0.31	224	225
TRAIL/TRAILR1/DAP3/GTP/FADD	0.015	0.063	-10000	0	-0.15	40	40
TRAIL/TRAILR2/FADD	0.012	0.07	0.16	64	-0.18	40	104
cell death	-0.001	0.049	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.007	0.065	-10000	0	-0.36	1	1
TRAILR2 (trimer)	-0.005	0.01	0.24	1	-10000	0	1
CASP8	-0.001	0.031	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.014	0.065	-10000	0	-0.16	47	47

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	-0.008	0.014	0.16	2	-0.18	2	4
SNTA1	-0.006	0	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	0.04	0.078	0.16	163	-0.18	2	165
MAPK12	0.01	0.061	0.14	82	-0.19	16	98
CCND1	-0.092	0.17	0.14	2	-0.37	150	152
p38 gamma/SNTA1	0.006	0.055	0.22	1	-0.18	16	17
MAP2K3	-0.007	0.018	-10000	0	-0.31	2	2
PKN1	-0.004	0.028	0.24	6	-0.31	1	7
G2/M transition checkpoint	0.01	0.061	0.14	82	-0.19	16	98
MAP2K6	0.015	0.07	0.16	86	-0.21	16	102
MAPT	0.002	0.028	0.16	2	-0.16	2	4
MAPK13	-0.007	0.017	0.2	2	-0.21	2	4
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	-0.007	0.042	0.16	5	-0.24	16	21

×

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	0.002	0.098	0.55	14	-0.98	1	15
oxygen homeostasis	0.024	0.043	0.18	17	-10000	0	17
TCEB2	-0.006	0	-10000	0	-10000	0	0
TCEB1	-0.006	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.011	0.11	0.39	1	-0.29	16	17
EPO	0.12	0.28	0.67	73	-10000	0	73
FIH (dimer)	0.023	0.045	0.19	13	-10000	0	13
APEX1	0.04	0.08	0.25	62	-10000	0	62
SERPINE1	0.15	0.33	0.71	101	-0.53	1	102
FLT1	-0.01	0.021	-10000	0	-10000	0	0
ADORA2A	0.13	0.3	0.67	79	-0.52	1	80
germ cell development	0.12	0.31	0.7	75	-0.62	2	77
SLC11A2	0.13	0.31	0.71	76	-0.53	1	77
BHLHE40	0.12	0.3	0.7	73	-0.53	1	74
HIF1AN	0.023	0.045	0.19	13	-10000	0	13
HIF2A/ARNT/SIRT1	0.006	0.15	0.42	7	-0.4	6	13
ETS1	-0.001	0.035	0.24	12	-10000	0	12
CITED2	-0.048	0.18	-10000	0	-0.84	27	27
KDR	-0.009	0.033	0.6	1	-10000	0	1
PGK1	0.18	0.36	0.76	101	-0.53	1	102
SIRT1	-0.006	0	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF2A/ARNT	0.14	0.33	0.77	72	-0.6	1	73
EPAS1	0.074	0.23	0.5	83	-0.33	12	95
SP1	0.002	0.045	0.24	19	-10000	0	19
ABCG2	0.11	0.32	0.7	72	-0.57	11	83
EFNA1	0.13	0.32	0.72	78	-0.53	1	79
FXN	0.13	0.3	0.67	79	-0.52	1	80
POU5F1	0.12	0.31	0.7	74	-0.64	2	76
neuron apoptosis	-0.14	0.33	0.58	1	-0.76	71	72
EP300	-0.007	0.018	-10000	0	-0.31	2	2
EGLN3	0.031	0.098	0.25	55	-0.3	16	71
EGLN2	0.024	0.047	0.19	17	-10000	0	17
EGLN1	0.023	0.045	0.19	13	-10000	0	13
VHL/Elongin B/Elongin C	0.01	0.011	0.16	3	-10000	0	3
VHL	-0.004	0.018	0.24	3	-10000	0	3
ARNT	0.02	0.047	0.21	14	-10000	0	14
SLC2A1	0.14	0.31	0.71	82	-0.52	1	83
TWIST1	0.13	0.3	0.67	79	-0.52	1	80
ELK1	-0.011	0.021	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.017	0.17	0.38	27	-0.4	6	33
VEGFA	0.14	0.32	0.74	81	-0.53	1	82
CREBBP	-0.012	0.042	-10000	0	-0.31	11	11

×

Retinoic acid receptors-mediated 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
HDAC1	0.01	0.06	0.24	36	-10000	0	36
HDAC3	-0.006	0	-10000	0	-10000	0	0
VDR	-0.005	0.01	0.24	1	-10000	0	1
Cbp/p300/PCAF	0.002	0.027	-10000	0	-0.18	13	13
EP300	-0.007	0.018	-10000	0	-0.31	2	2
RARs/AIB1/Cbp/p300/PCAF/9cRA	-0.024	0.045	0.18	1	-0.22	7	8
KAT2B	0	0	-10000	0	-10000	0	0
MAPK14	-0.005	0.01	0.24	1	-10000	0	1
AKT1	0.019	0.08	0.22	9	-10000	0	9
RAR alpha/9cRA/Cyclin H	-0.051	0.078	0.17	11	-0.26	17	28
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	-0.028	0.048	-10000	0	-0.23	10	10
CDC2	0.23	0.046	0.24	549	-10000	0	549
response to UV	-0.01	0.013	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.03	0.05	0.18	6	-0.16	4	10
NCOR2	-0.011	0.038	-10000	0	-0.31	9	9
VDR/VDR/Vit D3	-0.003	0.007	0.17	1	-10000	0	1
RXRs/RARs/NRIP1/9cRA	-0.16	0.26	-10000	0	-0.49	215	215
NCOA2	-0.005	0.015	0.24	2	-10000	0	2
NCOA3	-0.003	0.027	0.24	7	-10000	0	7
NCOA1	-0.007	0.018	-10000	0	-0.31	2	2
VDR/VDR/DNA	-0.005	0.01	0.24	1	-10000	0	1
RARG	-0.006	0.034	0.23	11	-10000	0	11
RAR gamma1/9cRA	0.001	0.018	0.15	6	-10000	0	6
MAPK3	-0.021	0.048	-10000	0	-0.32	14	14
MAPK1	-0.006	0.016	0.24	1	-0.31	1	2
MAPK8	-0.013	0.029	0.24	6	-10000	0	6
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.062	0.15	-10000	0	-0.34	22	22
RARA	-0.037	0.052	-10000	0	-0.2	4	4
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.027	0.048	-10000	0	-0.23	10	10
PRKCA	-0.027	0.045	0.2	7	-0.31	4	11
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.18	0.28	-10000	0	-0.53	218	218
RXRG	-0.037	0.061	-10000	0	-0.26	6	6
RXRA	0.02	0.092	0.2	4	-0.28	13	17
RXRB	-0.039	0.05	-10000	0	-0.24	4	4
VDR/Vit D3/DNA	-0.003	0.007	0.17	1	-10000	0	1
RBP1	-0.098	0.14	-10000	0	-0.31	174	174
CRBP1/9-cic-RA	-0.066	0.095	-10000	0	-0.21	174	174
RARB	-0.01	0.039	0.23	13	-10000	0	13
PRKCG	-0.027	0.027	-10000	0	-10000	0	0
MNAT1	-0.006	0	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.048	0.18	0.27	4	-0.39	17	21
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.065	0.14	-10000	0	-0.36	19	19
proteasomal ubiquitin-dependent protein catabolic process	-0.038	0.057	0.14	1	-0.24	7	8
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.18	0.28	-10000	0	-0.53	218	218
positive regulation of DNA binding	-0.052	0.068	-10000	0	-0.24	17	17
NRIP1	-0.38	0.52	-10000	0	-1	218	218
RXRs/RARs	-0.13	0.21	-10000	0	-0.39	217	217
RXRs/RXRs/DNA/9cRA	-0.064	0.16	-10000	0	-0.34	22	22
PRKACA	-0.006	0	-10000	0	-10000	0	0
CDK7	0.002	0.044	0.24	19	-10000	0	19
TFIIH	0.014	0.027	0.16	20	-10000	0	20
RAR alpha/9cRA	-0.028	0.041	0.12	14	-10000	0	14
CCNH	-0.005	0.01	0.24	1	-10000	0	1
CREBBP	-0.012	0.042	-10000	0	-0.31	11	11
RAR gamma2/9cRA	-0.013	0.004	-10000	0	-10000	0	0

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.064	0.12	0.24	54	-0.4	13	67
Syndecan-4/Syndesmos	0.05	0.09	0.24	48	-10000	0	48
positive regulation of JNK cascade	0.012	0.093	0.27	8	-0.3	10	18
Syndecan-4/ADAM12	0.084	0.13	0.29	135	-10000	0	135
CCL5	-0.029	0.088	0.24	6	-0.31	48	54
Rac1/GDP	-0.004	0.009	-10000	0	-0.21	1	1
DNM2	-0.005	0.01	0.24	1	-10000	0	1
ITGA5	-0.003	0.025	0.24	6	-10000	0	6
SDCBP	-0.006	0.023	0.24	2	-0.31	2	4
PLG	-0.018	0.046	-10000	0	-0.3	14	14
ADAM12	0.051	0.1	0.24	130	-10000	0	130
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	-0.006	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.006	0.006	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	0.075	0.1	0.26	71	-10000	0	71
Syndecan-4/CXCL12/CXCR4	0.032	0.11	0.24	54	-0.31	10	64
Syndecan-4/Laminin alpha3	0.048	0.093	0.25	47	-0.3	4	51
MDK	-0.005	0.01	0.24	1	-10000	0	1
Syndecan-4/FZD7	0.056	0.094	0.25	54	-10000	0	54
Syndecan-4/Midkine	0.051	0.09	0.24	48	-10000	0	48
FZD7	0.004	0.048	0.24	22	-10000	0	22
Syndecan-4/FGFR1/FGF	0.009	0.067	-10000	0	-0.29	3	3
THBS1	-0.036	0.1	0.24	8	-0.31	64	72
integrin-mediated signaling pathway	0.089	0.13	0.28	126	-10000	0	126
positive regulation of MAPKKK cascade	0.012	0.093	0.27	8	-0.3	10	18
Syndecan-4/TACI	0.05	0.09	0.24	48	-10000	0	48
CXCR4	-0.007	0.035	0.24	4	-0.31	5	9
cell adhesion	0.039	0.076	0.19	16	-0.21	13	29
Syndecan-4/Dynamin	0.051	0.09	0.24	48	-10000	0	48
Syndecan-4/TSP1	0.049	0.1	0.25	53	-0.3	9	62
Syndecan-4/GIPC	0.053	0.091	0.25	51	-10000	0	51
Syndecan-4/RANTES	0.05	0.098	0.26	50	-0.3	7	57
ITGB1	-0.003	0.025	0.24	6	-10000	0	6
LAMA1	0.036	0.093	0.24	96	-10000	0	96
LAMA3	-0.025	0.083	0.24	6	-0.31	41	47
RAC1	-0.006	0.013	-10000	0	-0.31	1	1
PRKCA	-0.022	0.057	0.34	7	-0.28	4	11
Syndecan-4/alpha-Actinin	0.049	0.093	0.24	47	-0.3	4	51
TFPI	-0.024	0.076	0.24	3	-0.31	36	39
F2	-0.002	0.017	0.27	1	-10000	0	1
alpha5/beta1 Integrin	-0.003	0.025	0.17	12	-10000	0	12
positive regulation of cell adhesion	0.062	0.1	0.25	71	-0.3	1	72
ACTN1	-0.012	0.042	-10000	0	-0.31	11	11
TNC	0.062	0.11	0.24	155	-10000	0	155
Syndecan-4/CXCL12	0.05	0.098	0.25	52	-0.3	9	61
FGF6	-0.006	0	-10000	0	-10000	0	0
RHOA	-0.007	0.018	-10000	0	-0.31	2	2
CXCL12	-0.045	0.11	0.24	9	-0.31	81	90
TNFRSF13B	-0.006	0	-10000	0	-10000	0	0
FGF2	-0.011	0.04	-10000	0	-0.31	10	10
FGFR1	-0.015	0.057	0.24	3	-0.31	19	22
Syndecan-4/PI-4-5-P2	0.05	0.088	0.24	48	-10000	0	48
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.08	0.13	0.25	200	-0.29	12	212
cell migration	-0.003	0.003	-10000	0	-10000	0	0
PRKCD	-0.011	0.023	0.25	1	-0.3	2	3
vasculogenesis	0.048	0.098	0.25	53	-0.29	9	62
SDC4	0.055	0.094	0.26	48	-10000	0	48
Syndecan-4/Tenascin C	0.09	0.13	0.29	126	-10000	0	126
Syndecan-4/PI-4-5-P2/PKC alpha	-0.005	0.005	-10000	0	-10000	0	0
Syndecan-4/Syntenin	0.051	0.091	0.24	48	-0.3	1	49
MMP9	0.034	0.094	0.25	92	-10000	0	92
Rac1/GTP	0.039	0.077	0.19	16	-0.22	13	29
cytoskeleton organization	0.05	0.089	0.24	48	-10000	0	48
GIPC1	-0.002	0.029	0.24	8	-10000	0	8
Syndecan-4/TFPI	0.048	0.094	0.25	48	-0.3	5	53

×

Syndecan-2-mediated signaling events

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
Syndecan-2/Fibronectin	0.048	0.096	0.17	204	-0.18	25	229
EPHB2	-0.001	0.033	0.24	10	-10000	0	10
Syndecan-2/TACI	-0.009	0.031	0.14	6	-0.18	15	21
LAMA1	0.036	0.093	0.24	96	-10000	0	96
Syndecan-2/alpha2 ITGB1	-0.024	0.061	0.14	18	-0.16	73	91
HRAS	-0.006	0	-10000	0	-10000	0	0
Syndecan-2/CASK	-0.006	0.031	0.14	6	-0.17	15	21
ITGA5	-0.003	0.025	0.24	6	-10000	0	6
BAX	-0.007	0.032	-10000	0	-10000	0	0
EPB41	0.006	0.052	0.24	26	-10000	0	26
positive regulation of cell-cell adhesion	-0.008	0.031	0.13	8	-0.16	17	25
LAMA3	-0.025	0.083	0.24	6	-0.31	41	47
EZR	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	-0.017	0.06	0.24	2	-0.31	22	24
Syndecan-2/MMP2	-0.02	0.081	0.16	38	-0.19	80	118
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	-0.013	0.045	0.17	6	-0.21	23	29
dendrite morphogenesis	-0.006	0.039	0.16	16	-0.18	15	31
Syndecan-2/GM-CSF	-0.009	0.031	0.14	6	-0.18	15	21
determination of left/right symmetry	-0.007	0.039	0.2	6	-0.21	15	21
Syndecan-2/PKC delta	-0.009	0.034	0.15	7	-0.18	17	24
GNB2L1	-0.006	0	-10000	0	-10000	0	0
MAPK3	-0.014	0.039	0.13	6	-0.18	26	32
MAPK1	-0.01	0.03	0.14	7	-0.16	16	23
Syndecan-2/RACK1	-0.009	0.027	0.12	6	-0.15	15	21
NF1	-0.02	0.063	-10000	0	-0.31	26	26
FGFR/FGF/Syndecan-2	-0.007	0.039	0.2	6	-0.21	15	21
ITGA2	-0.018	0.062	0.24	1	-0.31	24	25
MAPK8	-0.007	0.037	-10000	0	-10000	0	0
Syndecan-2/alpha2/beta1 Integrin	0.011	0.075	0.15	100	-0.16	33	133
Syndecan-2/Kininogen	-0.009	0.032	0.15	7	-0.18	15	22
ITGB1	-0.003	0.025	0.24	6	-10000	0	6
SRC	-0.011	0.025	-10000	0	-0.14	15	15
Syndecan-2/CASK/Protein 4.1	-0.001	0.041	0.15	30	-0.16	13	43
extracellular matrix organization	-0.035	0.072	0.14	6	-0.18	99	105
actin cytoskeleton reorganization	0.048	0.096	0.17	204	-0.18	25	229
Syndecan-2/Caveolin-2/Ras	-0.015	0.042	0.14	7	-0.17	34	41
Syndecan-2/Laminin alpha3	-0.019	0.057	0.16	12	-0.18	55	67
Syndecan-2/RasGAP	-0.012	0.027	0.12	6	-0.14	18	24
alpha5/beta1 Integrin	-0.003	0.025	0.17	12	-10000	0	12
PRKCD	-0.006	0.021	0.24	1	-0.31	2	3
Syndecan-2 dimer	-0.006	0.039	0.16	16	-0.18	15	31
GO:0007205	0	0	-10000	0	-10000	0	0
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	-0.013	0.027	-10000	0	-10000	0	0
RHOA	-0.007	0.018	-10000	0	-0.31	2	2
SDCBP	-0.006	0.023	0.24	2	-0.31	2	4
TNFRSF13B	-0.006	0	-10000	0	-10000	0	0
RASA1	-0.007	0.022	-10000	0	-0.31	3	3
alpha2/beta1 Integrin	-0.013	0.045	0.17	6	-0.21	23	29
Syndecan-2/Synbindin	0.002	0.053	0.17	41	-0.18	14	55
TGFB1	-0.054	0.11	-10000	0	-0.31	90	90
CASP3	-0.008	0.036	0.14	16	-0.16	16	32
FN1	0.075	0.13	0.24	200	-0.31	12	212
Syndecan-2/IL8	0.008	0.061	0.17	61	-0.18	14	75
SDC2	-0.007	0.039	0.2	6	-0.21	15	21
KNG1	-0.005	0.01	0.24	1	-10000	0	1
Syndecan-2/Neurofibromin	-0.017	0.045	0.14	4	-0.18	39	43
TRAPPC4	0.01	0.061	0.24	37	-10000	0	37
CSF2	-0.006	0	-10000	0	-10000	0	0
Syndecan-2/TGFB1	-0.036	0.072	0.14	6	-0.18	99	105
Syndecan-2/Syntenin/PI-4-5-P2	-0.008	0.031	0.13	8	-0.16	17	25
Syndecan-2/Ezrin	-0.008	0.029	0.13	6	-0.16	17	23
PRKACA	-0.017	0.04	-10000	0	-0.16	39	39
angiogenesis	0.008	0.061	0.17	61	-0.18	14	75
MMP2	-0.03	0.12	0.24	32	-0.31	71	103
IL8	0.019	0.074	0.24	57	-10000	0	57
calcineurin-NFAT signaling pathway	-0.009	0.031	0.14	6	-0.18	15	21

×

FoxO family signaling

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
G6PC	0.043	0.067	-10000	0	-10000	0	0
PLK1	0.22	0.31	0.71	71	-0.56	1	72
CDKN1B	0.14	0.24	0.54	66	-0.45	3	69
FOXO3	0.2	0.3	0.65	76	-0.49	14	90
KAT2B	0.043	0.053	0.13	78	-10000	0	78
FOXO1/SIRT1	0.004	0.051	-10000	0	-0.23	3	3
CAT	0.18	0.3	0.68	40	-0.91	7	47
CTNNB1	-0.005	0.015	0.24	2	-10000	0	2
AKT1	0.044	0.059	0.18	37	-10000	0	37
FOXO1	0.05	0.077	-10000	0	-10000	0	0
MAPK10	0.011	0.043	0.15	7	-0.16	7	14
mol:GTP	0	0.006	-10000	0	-10000	0	0
FOXO4	0.012	0.13	0.35	30	-0.42	4	34
response to oxidative stress	0.042	0.054	0.14	71	-10000	0	71
FOXO3A/SIRT1	0.091	0.26	0.58	53	-0.44	35	88
XPO1	0.015	0.067	0.24	46	-10000	0	46
EP300	-0.001	0.02	-10000	0	-0.31	2	2
BCL2L11	0.06	0.075	0.6	1	-10000	0	1
FOXO1/SKP2	0.082	0.11	0.27	90	-10000	0	90
mol:GDP	0.042	0.054	0.14	71	-10000	0	71
RAN	-0.005	0.007	-10000	0	-10000	0	0
GADD45A	0.14	0.23	0.57	77	-10000	0	77
YWHAQ	-0.006	0	-10000	0	-10000	0	0
FOXO1/14-3-3 family	0.018	0.033	-10000	0	-10000	0	0
MST1	0.044	0.058	0.17	40	-10000	0	40
CSNK1D	-0.006	0	-10000	0	-10000	0	0
CSNK1E	-0.006	0	-10000	0	-10000	0	0
FOXO4/14-3-3 family	0.005	0.035	-10000	0	-0.26	3	3
YWHAB	-0.005	0.01	0.24	1	-10000	0	1
MAPK8	0.015	0.042	0.15	8	-10000	0	8
MAPK9	0.013	0.04	0.15	7	-10000	0	7
YWHAG	-0.006	0	-10000	0	-10000	0	0
YWHAE	-0.006	0.013	-10000	0	-0.31	1	1
YWHAZ	-0.006	0	-10000	0	-10000	0	0
SIRT1	-0.005	0.025	-10000	0	-10000	0	0
SOD2	0.012	0.43	0.52	62	-0.76	112	174
RBL2	0.16	0.23	0.56	40	-0.89	1	41
RAL/GDP	0.031	0.045	0.2	5	-10000	0	5
CHUK	0.051	0.068	0.2	56	-10000	0	56
Ran/GTP	-0.002	0.012	-10000	0	-10000	0	0
CSNK1G2	-0.006	0	-10000	0	-10000	0	0
RAL/GTP	0.03	0.052	0.17	32	-10000	0	32
CSNK1G1	-0.006	0	-10000	0	-10000	0	0
FASLG	0.06	0.072	-10000	0	-10000	0	0
SKP2	0.059	0.11	0.24	149	-10000	0	149
USP7	-0.004	0.016	0.25	2	-10000	0	2
IKBKB	0.044	0.058	0.18	41	-10000	0	41
CCNB1	0.3	0.33	0.57	285	-0.56	1	286
FOXO1-3a-4/beta catenin	0.09	0.25	0.5	66	-0.43	7	73
proteasomal ubiquitin-dependent protein catabolic process	0.082	0.1	0.26	91	-10000	0	91
CSNK1A1	-0.005	0.015	0.24	2	-10000	0	2
SGK1	0.043	0.053	0.13	78	-10000	0	78
CSNK1G3	-0.006	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.009	0.043	0.16	39	-10000	0	39
ZFAND5	0.013	0.12	0.4	4	-0.85	1	5
SFN	0.003	0.047	0.24	21	-10000	0	21
CDK2	0.091	0.12	0.24	229	-10000	0	229
FOXO3A/14-3-3	0.067	0.087	0.24	42	-0.32	2	44
CREBBP	-0.016	0.042	-10000	0	-0.31	11	11
FBXO32	-0.072	0.57	0.68	43	-0.88	161	204
BCL6	0.14	0.29	0.56	41	-1	14	55
RALB	-0.006	0.007	-10000	0	-10000	0	0
RALA	-0.005	0.016	0.24	2	-10000	0	2
YWHAH	-0.007	0.022	-10000	0	-0.31	3	3

×

Cellular roles of Anthrax toxin

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
ANTXR1	-0.013	0.052	0.24	2	-0.31	16	18
ANTXR2	-0.012	0.049	0.24	2	-0.31	14	16
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.003	0.01	-10000	0	-0.046	27	27
monocyte activation	-0.028	0.14	0.27	1	-0.37	76	77
MAP2K2	-0.1	0.24	-10000	0	-0.66	92	92
MAP2K1	-0.005	0.011	0.13	1	-0.068	3	4
MAP2K7	-0.005	0.009	-10000	0	-10000	0	0
MAP2K6	0.014	0.048	0.13	82	-10000	0	82
CYAA	-0.011	0.036	0.12	4	-0.16	27	31
MAP2K4	-0.007	0.018	-10000	0	-0.15	6	6
IL1B	-0.002	0.042	0.12	40	-0.12	2	42
Channel	-0.002	0.041	0.15	4	-0.17	27	31
NLRP1	-0.005	0.01	0.09	1	-0.068	3	4
CALM1	-0.012	0.042	-10000	0	-0.31	11	11
negative regulation of phagocytosis	-0.011	0.065	-10000	0	-0.46	11	11
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.003	0.01	0.046	27	-10000	0	27
MAPK3	-0.009	0.024	-10000	0	-0.13	17	17
MAPK1	-0.005	0.012	0.13	1	-0.15	1	2
PGR	-0.14	0.037	-10000	0	-0.15	531	531
PA/Cellular Receptors	-0.002	0.045	0.15	4	-0.19	27	31
apoptosis	-0.003	0.01	-10000	0	-0.046	27	27
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.002	0.04	0.14	4	-0.17	27	31
macrophage activation	-0.01	0.024	0.12	1	-0.14	15	16
TNF	-0.005	0.01	0.24	1	-10000	0	1
VCAM1	-0.028	0.14	0.27	1	-0.37	76	77
platelet activation	-0.011	0.065	-10000	0	-0.46	11	11
MAPKKK cascade	0.008	0.027	0.062	71	-10000	0	71
IL18	0.013	0.058	0.12	107	-0.12	2	109
negative regulation of macrophage activation	-0.003	0.01	-10000	0	-0.046	27	27
LEF	-0.003	0.01	-10000	0	-0.047	27	27
CASP1	-0.004	0.011	0.04	1	-0.05	24	25
mol:cAMP	-0.011	0.065	-10000	0	-0.47	11	11
necrosis	-0.003	0.01	-10000	0	-0.046	27	27
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.002	0.039	0.14	4	-0.16	27	31
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	-0.16	0.36	-10000	0	-0.99	90	90
VDR	-0.005	0.01	0.24	1	-10000	0	1
FAM120B	-0.007	0.022	-10000	0	-0.31	3	3
RXRs/LXRs/DNA/9cRA	0.014	0.093	0.32	36	-0.31	2	38
RXRs/LXRs/DNA/Oxysterols	0.018	0.11	0.4	36	-0.45	2	38
MED1	-0.005	0.015	0.24	2	-10000	0	2
mol:9cRA	0.007	0.021	0.1	2	-10000	0	2
RARs/THRs/DNA/Src-1	-0.038	0.087	0.21	1	-0.19	127	128
RXRs/NUR77	-0.049	0.1	0.21	23	-0.29	6	29
RXRs/PPAR	0.007	0.047	0.23	2	-0.19	10	12
NCOR2	-0.011	0.038	-10000	0	-0.31	9	9
VDR/VDR/Vit D3	-0.003	0.007	0.17	1	-10000	0	1
RARs/VDR/DNA/Vit D3	0.016	0.027	0.14	25	-10000	0	25
RARA	-0.006	0	-10000	0	-10000	0	0
NCOA1	-0.007	0.018	-10000	0	-0.31	2	2
VDR/VDR/DNA	-0.005	0.01	0.24	1	-10000	0	1
RARs/RARs/DNA/9cRA	0.018	0.029	0.14	24	-10000	0	24
RARG	-0.001	0.034	0.24	11	-10000	0	11
RPS6KB1	-0.062	0.15	0.35	9	-0.4	89	98
RARs/THRs/DNA/SMRT	-0.041	0.091	0.21	1	-0.19	132	133
THRA	-0.079	0.13	-10000	0	-0.31	138	138
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	-0.003	0.007	0.17	1	-10000	0	1
RXRs/PPAR/9cRA/PGJ2/DNA	0.044	0.11	0.25	119	-10000	0	119
NR1H4	-0.004	0.023	0.24	5	-10000	0	5
RXRs/LXRs/DNA	0.017	0.094	0.31	36	-0.27	1	37
NR1H2	-0.01	0.057	-10000	0	-0.31	17	17
NR1H3	-0.001	0.024	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.018	0.067	0.19	40	-10000	0	40
NR4A1	-0.12	0.15	0.24	4	-0.31	228	232
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	0.012	0.051	0.22	2	-10000	0	2
RXRG	0.009	0.047	0.24	15	-0.31	1	16
RXR alpha/CCPG	-0.005	0.04	-10000	0	-0.2	18	18
RXRA	-0.004	0.054	-10000	0	-0.3	15	15
RXRB	0.004	0.025	-10000	0	-10000	0	0
THRB	0.006	0.053	0.24	27	-10000	0	27
PPARG	-0.004	0.023	0.24	5	-10000	0	5
PPARD	-0.006	0	-10000	0	-10000	0	0
TNF	0.017	0.1	0.45	3	-0.46	1	4
mol:Oxysterols	0.004	0.019	-10000	0	-10000	0	0
cholesterol transport	0.018	0.11	0.39	36	-0.44	2	38
PPARA	-0.006	0	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0	0.037	0.24	13	-10000	0	13
RXRs/NUR77/BCL2	-0.1	0.12	0.19	2	-0.22	262	264
SREBF1	0.013	0.12	0.42	2	-0.86	4	6
RXRs/RXRs/DNA/9cRA	0.043	0.11	0.25	119	-10000	0	119
ABCA1	0.027	0.14	0.51	35	-0.46	1	36
RARs/THRs	-0.016	0.081	0.28	1	-0.15	127	128
RXRs/FXR	0.02	0.073	0.2	41	-10000	0	41
BCL2	-0.055	0.11	0.24	1	-0.31	93	94

×

IL2 signaling events mediated by PI3K

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
BCL2L1	-0.031	0.092	0.6	1	-10000	0	1
UGCG	-0.016	0.038	-10000	0	-0.59	1	1
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.09	0.15	-10000	0	-0.4	62	62
mol:GTP	0	0.001	-10000	0	-10000	0	0
mol:glucosylceramide	-0.015	0.039	-10000	0	-0.58	1	1
mol:DAG	-0.013	0.1	-10000	0	-0.88	8	8
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.13	0.19	-10000	0	-0.45	126	126
FRAP1	-0.14	0.23	-10000	0	-0.54	110	110
FOXO3	-0.1	0.18	-10000	0	-0.49	71	71
AKT1	-0.11	0.19	-10000	0	-0.52	74	74
GAB2	-0.008	0.061	0.24	15	-0.31	13	28
SMPD1	-0.015	0.029	-10000	0	-10000	0	0
SGMS1	-0.024	0.086	-10000	0	-0.7	8	8
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	-0.014	0.097	0.14	98	-0.18	107	205
CALM1	-0.012	0.042	-10000	0	-0.31	11	11
cell proliferation	-0.05	0.1	-10000	0	-0.28	66	66
EIF3A	-0.006	0	-10000	0	-10000	0	0
PI3K	-0.018	0.12	0.17	95	-0.21	107	202
RPS6KB1	-0.02	0.06	0.39	1	-10000	0	1
mol:sphingomyelin	-0.013	0.1	-10000	0	-0.88	8	8
natural killer cell activation	-0.002	0.004	-10000	0	-10000	0	0
JAK3	-0.008	0.005	-10000	0	-10000	0	0
PIK3R1	-0.077	0.13	-10000	0	-0.31	131	131
JAK1	-0.009	0.019	-10000	0	-0.31	2	2
NFKB1	-0.01	0.033	-10000	0	-0.31	7	7
MYC	-0.14	0.28	-10000	0	-0.92	59	59
MYB	-0.071	0.27	0.53	1	-1.1	37	38
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.067	0.13	0.27	1	-0.36	41	42
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.018	0.055	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.066	0.12	0.27	1	-0.36	37	38
Rac1/GDP	-0.019	0.085	0.13	77	-0.16	107	184
T cell proliferation	-0.064	0.12	0.26	1	-0.34	36	37
SHC1	-0.008	0.003	-10000	0	-10000	0	0
RAC1	-0.007	0.013	-10000	0	-0.31	1	1
positive regulation of cyclin-dependent protein kinase activity	-0.004	0.017	0.18	1	-0.063	37	38
PRKCZ	-0.066	0.12	0.26	1	-0.36	36	37
NF kappa B1 p50/RelA	-0.12	0.2	-10000	0	-0.46	116	116
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.033	0.098	0.49	1	-0.34	8	9
HSP90AA1	-0.006	0.013	-10000	0	-0.31	1	1
RELA	-0.006	0.013	-10000	0	-0.31	1	1
IL2RA	-0.005	0.026	0.24	6	-10000	0	6
IL2RB	-0.008	0.021	0.24	1	-0.31	2	3
TERT	-0.006	0	-10000	0	-10000	0	0
E2F1	-0.028	0.11	0.47	1	-0.43	37	38
SOS1	0.003	0.05	0.24	24	-10000	0	24
RPS6	-0.006	0	-10000	0	-10000	0	0
mol:cAMP	0.002	0.009	0.036	2	-0.12	1	3
PTPN11	-0.008	0.004	-10000	0	-10000	0	0
IL2RG	-0.011	0.09	0.24	30	-0.31	30	60
actin cytoskeleton organization	-0.064	0.12	0.26	1	-0.34	36	37
GRB2	-0.008	0.004	-10000	0	-10000	0	0
IL2	-0.008	0.005	-10000	0	-10000	0	0
PIK3CA	0.045	0.1	0.24	122	-10000	0	122
Rac1/GTP	-0.012	0.083	0.23	1	-0.15	107	108
LCK	-0.008	0.006	-10000	0	-10000	0	0
BCL2	-0.17	0.3	-10000	0	-0.8	96	96

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	-0.09	0.087	0.21	3	-0.24	9	12
CaM/Ca2+	-0.007	0.028	-10000	0	-0.21	11	11
AKT1	-0.005	0.01	0.24	1	-10000	0	1
AKT2	-0.004	0.023	0.24	5	-10000	0	5
STXBP4	-0.005	0.015	0.24	2	-10000	0	2
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	-0.034	0.063	-10000	0	-10000	0	0
YWHAZ	-0.006	0	-10000	0	-10000	0	0
CALM1	-0.012	0.042	-10000	0	-0.31	11	11
YWHAQ	-0.006	0	-10000	0	-10000	0	0
TBC1D4	-0.006	0.012	0.2	2	-10000	0	2
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	-0.007	0.022	-10000	0	-0.31	3	3
YWHAB	-0.005	0.01	0.24	1	-10000	0	1
SNARE/Synip	-0.13	0.082	-10000	0	-0.18	417	417
YWHAG	-0.006	0	-10000	0	-10000	0	0
ASIP	-0.007	0.024	0.24	1	-0.31	3	4
PRKCI	0.1	0.12	0.24	255	-10000	0	255
AS160/CaM/Ca2+	-0.007	0.028	-10000	0	-0.21	11	11
RHOQ	-0.004	0.018	0.24	3	-10000	0	3
GYS1	-0.003	0.013	-10000	0	-10000	0	0
PRKCZ	-0.006	0	-10000	0	-10000	0	0
TRIP10	-0.006	0	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.007	0.011	0.15	3	-10000	0	3
AS160/14-3-3	-0.001	0.024	-10000	0	-10000	0	0
VAMP2	-0.23	0.13	-10000	0	-0.31	419	419
SLC2A4	-0.037	0.067	-10000	0	-10000	0	0
STX4	-0.006	0	-10000	0	-10000	0	0
GSK3B	-0.001	0.016	-10000	0	-10000	0	0
SFN	0.003	0.047	0.24	21	-10000	0	21
LNPEP	0.001	0.045	0.24	18	-0.31	1	19
YWHAE	-0.006	0.013	-10000	0	-0.31	1	1

×

Aurora C signaling

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
INCENP	-0.005	0.015	0.24	2	-10000	0	2
Aurora C/Aurora B/INCENP	0.038	0.058	0.15	120	-10000	0	120
metaphase	0	0	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
H3F3B	-0.006	0.046	-10000	0	-0.41	7	7
AURKB	0.046	0.1	0.24	119	-10000	0	119
AURKC	-0.006	0	-10000	0	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	0.011	0.052	0.18	30	-0.18	1	31
CRKL	-0.006	0	-10000	0	-10000	0	0
Rac1/GDP	-0.004	0.009	-10000	0	-0.21	1	1
DOCK1	-0.006	0.021	0.24	1	-0.31	2	3
ITGA4	0.007	0.055	0.24	30	-10000	0	30
alpha4/beta7 Integrin/MAdCAM1	0.018	0.035	0.16	30	-0.16	3	33
EPO	-0.006	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	0.002	0.043	0.18	30	-0.21	1	31
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.005	0.01	0.24	1	-10000	0	1
alpha4/beta1 Integrin	0.004	0.046	0.18	34	-10000	0	34
EPO/EPOR (dimer)	-0.007	0.007	0.17	1	-10000	0	1
lamellipodium assembly	-0.025	0.1	-10000	0	-0.48	3	3
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
PI3K	-0.015	0.12	0.17	98	-0.21	107	205
ARF6	-0.006	0.013	-10000	0	-0.31	1	1
JAK2	0.002	0.036	0.22	4	-0.26	2	6
PXN	-0.01	0.033	-10000	0	-0.31	7	7
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
MADCAM1	-0.006	0	-10000	0	-10000	0	0
cell adhesion	0.017	0.034	0.29	1	-0.16	3	4
CRKL/CBL	-0.007	0	-10000	0	-10000	0	0
ITGB1	-0.003	0.025	0.24	6	-10000	0	6
SRC	-0.001	0.09	0.15	104	-0.16	76	180
ITGB7	-0.006	0.016	0.24	1	-0.31	1	2
RAC1	-0.006	0.013	-10000	0	-0.31	1	1
alpha4/beta1 Integrin/VCAM1	0.007	0.09	0.16	90	-0.18	76	166
p130Cas/Crk/Dock1	-0.007	0.077	0.21	14	-10000	0	14
VCAM1	-0.01	0.14	0.24	83	-0.31	76	159
RHOA	-0.007	0.018	-10000	0	-0.31	2	2
alpha4/beta1 Integrin/Paxillin/GIT1	0.018	0.041	0.16	34	-0.16	6	40
BCAR1	-0.003	0.085	0.26	14	-0.15	77	91
EPOR	-0.005	0.01	0.24	1	-10000	0	1
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	-0.006	0	-10000	0	-10000	0	0
GIT1	-0.005	0.01	0.24	1	-10000	0	1
Rac1/GTP	-0.026	0.11	-10000	0	-0.5	3	3

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	-0.005	0.01	0.24	1	-10000	0	1
LAT2	-0.008	0.074	-10000	0	-0.26	30	30
AP1	-0.016	0.091	0.26	5	-0.34	19	24
mol:PIP3	-0.012	0.085	0.16	18	-0.29	32	50
IKBKB	-0.006	0.054	0.12	18	-0.18	28	46
AKT1	-0.031	0.099	0.19	19	-0.26	30	49
IKBKG	-0.006	0.054	0.12	18	-0.18	28	46
MS4A2	-0.003	0.008	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
MAP3K1	-0.009	0.078	0.16	17	-0.27	26	43
mol:Ca2+	-0.008	0.07	0.14	19	-0.23	32	51
LYN	-0.013	0.051	-10000	0	-0.32	15	15
CBLB	-0.007	0.074	0.19	1	-0.26	30	31
SHC1	-0.006	0	-10000	0	-10000	0	0
RasGAP/p62DOK	-0.026	0.069	0.15	3	-0.16	119	122
positive regulation of cell migration	-0.006	0.021	-10000	0	-0.21	6	6
INPP5D	0	0	-10000	0	-10000	0	0
PLD2	-0.022	0.07	-10000	0	-0.16	74	74
PTPN13	-0.02	0.11	0.35	1	-0.4	17	18
PTPN11	-0.005	0.006	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	-0.017	0.09	0.18	29	-0.23	21	50
SYK	-0.007	0.035	0.24	2	-0.32	6	8
GRB2	-0.005	0.003	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.03	0.069	-10000	0	-0.29	32	32
LAT	-0.008	0.073	-10000	0	-0.26	30	30
PAK2	-0.008	0.084	0.17	17	-0.29	26	43
NFATC2	-0.022	0.082	-10000	0	-0.42	23	23
HRAS	-0.007	0.088	0.18	18	-0.31	26	44
GAB2	-0.006	0.061	0.24	15	-0.31	13	28
PLA2G1B	-0.018	0.038	-10000	0	-10000	0	0
Fc epsilon R1	0.005	0.066	0.15	72	-0.16	31	103
Antigen/IgE/Fc epsilon R1	0.006	0.061	0.14	72	-0.14	31	103
mol:GDP	-0.007	0.093	0.2	18	-0.32	27	45
JUN	-0.001	0.042	0.24	14	-0.31	2	16
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	-0.073	0.13	-10000	0	-0.31	131	131
FOS	-0.029	0.11	0.24	26	-0.31	65	91
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.006	0.077	-10000	0	-0.26	32	32
CHUK	-0.003	0.056	0.12	25	-0.18	27	52
KLRG1	-0.005	0.066	-10000	0	-0.21	36	36
VAV1	-0.008	0.075	0.2	1	-0.26	32	33
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.008	0.073	-10000	0	-0.26	30	30
negative regulation of mast cell degranulation	-0.006	0.061	-10000	0	-0.2	31	31
BTK	-0.008	0.092	0.22	19	-0.32	27	46
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	0.004	0.068	0.2	29	-0.2	5	34
GAB2/PI3K/SHP2	-0.056	0.075	-10000	0	-0.17	142	142
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.006	0.076	-10000	0	-0.24	38	38
RAF1	0.002	0.012	-10000	0	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	0.022	0.077	0.18	77	-0.14	30	107
FCER1G	0.007	0.11	0.23	69	-0.31	31	100
FCER1A	-0.003	0.018	0.24	3	-10000	0	3
Antigen/IgE/Fc epsilon R1/Fyn	-0.016	0.08	0.14	68	-0.16	97	165
MAPK3	-0.018	0.042	-10000	0	-10000	0	0
MAPK1	-0.015	0.033	-10000	0	-10000	0	0
NFKB1	-0.01	0.033	-10000	0	-0.31	7	7
MAPK8	0.003	0.052	-10000	0	-0.4	6	6
DUSP1	-0.065	0.12	0.24	3	-0.31	114	117
NF-kappa-B/RelA	-0.013	0.031	-10000	0	-0.16	16	16
actin cytoskeleton reorganization	0.002	0.087	-10000	0	-0.38	12	12
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.019	0.12	0.22	14	-0.32	28	42
FER	-0.008	0.073	-10000	0	-0.26	30	30
RELA	-0.006	0.013	-10000	0	-0.31	1	1
ITK	0.002	0.032	0.16	13	-10000	0	13
SOS1	0.005	0.05	0.24	24	-10000	0	24
PLCG1	-0.008	0.088	0.19	18	-0.3	29	47
cytokine secretion	-0.011	0.022	-10000	0	-0.14	7	7
SPHK1	-0.008	0.073	-10000	0	-0.26	30	30
PTK2	0.002	0.09	-10000	0	-0.39	12	12
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.029	0.071	-10000	0	-0.3	32	32
EDG1	-0.006	0.021	-10000	0	-0.21	6	6
mol:DAG	-0.011	0.084	0.18	5	-0.29	30	35
MAP2K2	-0.026	0.056	-10000	0	-10000	0	0
MAP2K1	-0.001	0.012	-10000	0	-10000	0	0
MAP2K7	-0.006	0	-10000	0	-10000	0	0
KLRG1/SHP2	-0.015	0.048	-10000	0	-0.24	15	15
MAP2K4	-0.003	0.086	-10000	0	-0.84	6	6
Fc epsilon R1/FcgammaRIIB	0.024	0.083	0.2	77	-0.15	30	107
mol:Choline	-0.022	0.069	-10000	0	-0.15	74	74
SHC/Grb2/SOS1	-0.003	0.076	0.23	2	-0.25	27	29
FYN	-0.047	0.1	0.24	1	-0.31	79	80
DOK1	-0.007	0.018	-10000	0	-0.31	2	2
PXN	-0.002	0.086	-10000	0	-0.37	12	12
HCLS1	-0.005	0.081	0.22	7	-0.27	30	37
PRKCB	-0.008	0.068	0.14	19	-0.23	32	51
FCGR2B	0.008	0.06	0.24	34	-0.31	1	35
IGHE	0	0.003	-10000	0	-10000	0	0
KLRG1/SHIP	-0.006	0.062	-10000	0	-0.21	31	31
LCP2	-0.014	0.053	-10000	0	-0.31	18	18
PLA2G4A	-0.074	0.1	-10000	0	-0.33	34	34
RASA1	-0.007	0.022	-10000	0	-0.31	3	3
mol:Phosphatidic acid	-0.022	0.069	-10000	0	-0.15	74	74
IKK complex	-0.003	0.046	0.13	8	-0.15	15	23
WIPF1	-0.006	0	-10000	0	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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
CRKL	-0.006	0	-10000	0	-10000	0	0
Rac1/GDP	0.005	0.014	-10000	0	-0.3	1	1
DOCK1	-0.006	0.021	0.24	1	-0.31	2	3
ITGA4	0.007	0.055	0.24	30	-10000	0	30
RAC1	-0.006	0.013	-10000	0	-0.31	1	1
alpha4/beta7 Integrin	0.002	0.043	0.18	30	-0.21	1	31
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.005	0.01	0.24	1	-10000	0	1
alpha4/beta1 Integrin	0.017	0.034	0.16	32	-10000	0	32
alpha4/beta7 Integrin/Paxillin	-0.003	0.041	0.16	29	-0.16	7	36
lamellipodium assembly	-0.053	0.14	-10000	0	-0.31	107	107
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
PI3K	-0.015	0.12	0.17	98	-0.21	107	205
ARF6	-0.006	0.013	-10000	0	-0.31	1	1
TLN1	-0.006	0.013	-10000	0	-0.31	1	1
PXN	-0.009	0.023	-10000	0	-0.21	7	7
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
ARF6/GTP	-0.006	0.036	0.12	34	-10000	0	34
cell adhesion	-0.003	0.043	0.15	33	-0.29	1	34
CRKL/CBL	-0.007	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	-0.001	0.044	0.16	33	-0.16	6	39
ITGB1	-0.003	0.025	0.24	6	-10000	0	6
ITGB7	-0.006	0.016	0.24	1	-0.31	1	2
ARF6/GDP	0.005	0.014	-10000	0	-0.3	1	1
alpha4/beta1 Integrin/Paxillin/VCAM1	0.001	0.095	0.3	14	-10000	0	14
p130Cas/Crk/Dock1	0.008	0.016	0.16	2	-0.18	3	5
VCAM1	-0.01	0.14	0.24	83	-0.31	76	159
alpha4/beta1 Integrin/Paxillin/Talin	-0.003	0.044	0.16	33	-0.29	1	34
alpha4/beta1 Integrin/Paxillin/GIT1	-0.003	0.043	0.16	34	-10000	0	34
BCAR1	-0.006	0.013	-10000	0	-0.31	1	1
mol:GDP	0.003	0.042	-10000	0	-0.15	34	34
CBL	-0.006	0	-10000	0	-10000	0	0
PRKACA	-0.006	0	-10000	0	-10000	0	0
GIT1	-0.005	0.01	0.24	1	-10000	0	1
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.003	0.044	0.16	33	-0.29	1	34
Rac1/GTP	-0.059	0.15	-10000	0	-0.34	107	107

×

Signaling events mediated by PTP1B

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
PDGFRB	-0.01	0.033	-10000	0	-0.31	7	7
Jak2/Leptin Receptor	0.002	0.063	0.22	2	-0.4	3	5
PTP1B/AKT1	-0.012	0.077	-10000	0	-0.26	7	7
FYN	-0.047	0.1	0.24	1	-0.31	79	80
p210 bcr-abl/PTP1B	-0.008	0.085	-10000	0	-0.24	19	19
EGFR	-0.027	0.086	0.24	1	-0.32	46	47
EGF/EGFR	-0.036	0.075	0.21	3	-0.28	25	28
CSF1	-0.018	0.06	0.24	1	-0.31	23	24
AKT1	-0.006	0.011	0.24	1	-10000	0	1
INSR	-0.034	0.089	-10000	0	-0.31	53	53
PTP1B/N-cadherin	0.008	0.11	0.22	30	-0.27	29	59
Insulin Receptor/Insulin	-0.024	0.077	-10000	0	-0.28	14	14
HCK	-0.005	0.01	0.24	1	-10000	0	1
CRK	-0.005	0.01	0.24	1	-10000	0	1
TYK2	-0.01	0.081	-10000	0	-0.24	19	19
EGF	0	0.028	0.24	7	-10000	0	7
YES1	0.006	0.052	0.24	26	-10000	0	26
CAV1	-0.036	0.1	-10000	0	-0.31	33	33
TXN	-0.014	0.058	-10000	0	-0.31	20	20
PTP1B/IRS1/GRB2	-0.094	0.1	-10000	0	-0.29	56	56
cell migration	0.008	0.085	0.24	19	-10000	0	19
STAT3	-0.011	0.04	-10000	0	-0.31	10	10
PRLR	0.003	0.046	0.24	20	-10000	0	20
ITGA2B	-0.006	0.003	-10000	0	-10000	0	0
CSF1R	-0.006	0.03	0.24	4	-0.31	3	7
Prolactin Receptor/Prolactin	0	0.035	0.17	22	-10000	0	22
FGR	-0.006	0	-10000	0	-10000	0	0
PTP1B/p130 Cas	-0.01	0.081	-10000	0	-0.24	19	19
Crk/p130 Cas	-0.01	0.08	-10000	0	-0.26	7	7
DOK1	-0.017	0.081	-10000	0	-0.29	8	8
JAK2	0	0.061	-10000	0	-0.46	2	2
Jak2/Leptin Receptor/Leptin	-0.022	0.071	0.17	2	-0.33	5	7
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
PTPN1	-0.009	0.086	-10000	0	-0.25	19	19
LYN	-0.014	0.048	-10000	0	-0.31	15	15
CDH2	-0.003	0.15	0.24	101	-0.31	77	178
SRC	0.001	0.036	-10000	0	-10000	0	0
ITGB3	-0.041	0.11	0.24	12	-0.31	77	89
CAT1/PTP1B	-0.024	0.092	-10000	0	-0.31	10	10
CAPN1	-0.006	0.019	-10000	0	-0.31	2	2
CSK	-0.006	0	-10000	0	-10000	0	0
PI3K	-0.045	0.094	-10000	0	-0.26	39	39
mol:H2O2	0	0.003	-10000	0	-10000	0	0
STAT3 (dimer)	-0.021	0.067	0.22	1	-0.34	5	6
negative regulation of transcription	0	0.06	-10000	0	-0.46	2	2
FCGR2A	-0.007	0.045	0.24	7	-0.31	8	15
FER	-0.002	0.012	0.24	1	-10000	0	1
alphaIIb/beta3 Integrin	-0.027	0.078	0.17	12	-0.22	77	89
BLK	-0.005	0.01	0.24	1	-10000	0	1
Insulin Receptor/Insulin/Shc	-0.013	0.054	-10000	0	-0.18	53	53
RHOA	-0.006	0.019	-10000	0	-0.31	2	2
LEPR	-0.004	0.026	0.24	5	-0.31	1	6
BCAR1	-0.006	0.013	-10000	0	-0.31	1	1
p210 bcr-abl/Grb2	-0.006	0	-10000	0	-10000	0	0
mol:NADPH	0	0.002	-10000	0	-10000	0	0
TRPV6	-0.026	0.076	-10000	0	-0.22	18	18
PRL	-0.005	0.011	0.24	1	-10000	0	1
SOCS3	-0.002	0.075	0.53	2	-1.1	2	4
SPRY2	-0.028	0.12	0.24	40	-0.31	72	112
Insulin Receptor/Insulin/IRS1	-0.13	0.1	-10000	0	-0.2	368	368
CSF1/CSF1R	-0.015	0.089	0.27	1	-0.27	13	14
Ras protein signal transduction	-0.003	0.027	-10000	0	-10000	0	0
IRS1	-0.2	0.15	-10000	0	-0.31	357	357
INS	-0.006	0.003	-10000	0	-10000	0	0
LEP	-0.005	0.003	-10000	0	-10000	0	0
STAT5B	-0.007	0.078	-10000	0	-0.26	11	11
STAT5A	-0.006	0.074	-10000	0	-0.23	9	9
GRB2	-0.006	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.011	0.082	-10000	0	-0.24	20	20
CSN2	0.003	0.034	0.51	1	-10000	0	1
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
LAT	-0.004	0.07	-10000	0	-0.48	8	8
YBX1	-0.008	0.003	-10000	0	-10000	0	0
LCK	-0.006	0	-10000	0	-10000	0	0
SHC1	-0.006	0	-10000	0	-10000	0	0
NOX4	0.082	0.12	0.24	202	-10000	0	202

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	-0.009	0.011	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.035	0.068	0.22	8	-0.27	1	9
ERC1	-0.005	0.024	0.24	4	-0.31	1	5
RIP2/NOD2	0.049	0.083	0.17	180	-10000	0	180
NFKBIA	-0.022	0.057	-10000	0	-0.38	13	13
BIRC2	0.059	0.11	0.24	149	-10000	0	149
IKBKB	-0.005	0.015	0.24	2	-10000	0	2
RIPK2	0.073	0.12	0.24	180	-10000	0	180
IKBKG	0.045	0.063	0.18	61	-10000	0	61
IKK complex/A20	0.017	0.047	0.25	3	-10000	0	3
NEMO/A20/RIP2	0.072	0.12	0.24	180	-10000	0	180
XPO1	0.014	0.068	0.24	46	-10000	0	46
NEMO/ATM	0.055	0.075	0.27	25	-10000	0	25
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	-0.006	0	-10000	0	-10000	0	0
Exportin 1/RanGTP	0.018	0.04	0.15	46	-10000	0	46
IKK complex/ELKS	-0.002	0.016	-10000	0	-10000	0	0
BCL10/MALT1/TRAF6	0.019	0.038	0.16	40	-10000	0	40
NOD2	-0.005	0.01	0.24	1	-10000	0	1
NFKB1	-0.013	0.037	-10000	0	-0.33	7	7
RELA	-0.01	0.017	-10000	0	-0.31	1	1
MALT1	0.011	0.062	0.24	38	-10000	0	38
cIAP1/UbcH5C	0.039	0.078	0.17	149	-10000	0	149
ATM	0.002	0.043	0.24	18	-10000	0	18
TNF/TNFR1A	-0.013	0.038	0.17	1	-0.21	19	20
TRAF6	-0.005	0.015	0.24	2	-10000	0	2
PRKCA	-0.005	0.037	0.24	7	-0.31	4	11
CHUK	0.002	0.043	0.24	18	-10000	0	18
UBE2D3	-0.006	0	-10000	0	-10000	0	0
TNF	-0.005	0.01	0.24	1	-10000	0	1
NF kappa B1 p50/RelA	-0.019	0.038	-10000	0	-0.22	19	19
BCL10	-0.006	0	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.022	0.057	-10000	0	-0.38	13	13
beta TrCP1/SCF ubiquitin ligase complex	-0.009	0.011	-10000	0	-10000	0	0
TNFRSF1A	-0.016	0.054	-10000	0	-0.31	19	19
IKK complex	0.049	0.067	0.24	14	-10000	0	14
CYLD	-0.006	0	-10000	0	-10000	0	0
IKK complex/PKC alpha	0.027	0.054	0.23	15	-10000	0	15

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.13	0.19	0.47	1	-0.52	36	37
RAD9A	-0.006	0	-10000	0	-10000	0	0
AP1	-0.024	0.086	0.19	32	-0.22	66	98
IFNAR2	-0.009	0.012	0.22	1	-10000	0	1
AKT1	-0.029	0.049	0.16	1	-0.17	19	20
ER alpha/Oestrogen	-0.033	0.069	-10000	0	-0.21	75	75
NFX1/SIN3/HDAC complex	-0.001	0.039	0.21	2	-10000	0	2
EGF	-0.005	0.027	0.24	7	-10000	0	7
SMG5	-0.004	0.018	0.24	3	-10000	0	3
SMG6	-0.006	0	-10000	0	-10000	0	0
SP3/HDAC2	-0.01	0.026	0.16	9	-0.23	1	10
TERT/c-Abl	-0.12	0.18	-10000	0	-0.47	54	54
SAP18	-0.007	0.013	-10000	0	-0.31	1	1
MRN complex	0.034	0.057	0.16	99	-0.18	2	101
WT1	-0.027	0.07	-10000	0	-0.31	32	32
WRN	0.012	0.063	0.24	40	-10000	0	40
SP1	-0.012	0.01	-10000	0	-10000	0	0
SP3	-0.008	0.005	-10000	0	-10000	0	0
TERF2IP	-0.006	0	-10000	0	-10000	0	0
Telomerase/Nucleolin	-0.12	0.18	-10000	0	-0.46	60	60
Mad/Max	-0.01	0.014	0.16	3	-10000	0	3
TERT	-0.13	0.2	0.47	1	-0.54	29	30
CCND1	-0.27	0.44	0.58	1	-1	150	151
MAX	-0.008	0.005	-10000	0	-10000	0	0
RBBP7	-0.008	0.018	-10000	0	-0.31	2	2
RBBP4	0.001	0.043	0.24	18	-10000	0	18
TERF2	-0.008	0.001	-10000	0	-10000	0	0
PTGES3	-0.055	0.11	-10000	0	-0.31	93	93
SIN3A	-0.007	0.002	-10000	0	-10000	0	0
Telomerase/911	-0.02	0.085	0.24	2	-10000	0	2
CDKN1B	-0.002	0.071	0.36	12	-0.37	3	15
RAD1	0.004	0.049	0.24	23	-10000	0	23
XRCC5	0.008	0.056	0.24	31	-10000	0	31
XRCC6	-0.006	0	-10000	0	-10000	0	0
SAP30	-0.007	0.002	-10000	0	-10000	0	0
TRF2/PARP2	0.01	0.053	0.16	60	-10000	0	60
UBE3A	-0.008	0.004	-10000	0	-10000	0	0
JUN	-0.003	0.043	0.24	14	-0.31	2	16
E6	-0.002	0.004	-10000	0	-10000	0	0
HPV-16 E6/E6AP	-0.007	0.006	-10000	0	-10000	0	0
FOS	-0.031	0.11	0.24	26	-0.31	65	91
IFN-gamma/IRF1	-0.005	0.06	0.2	32	-0.22	10	42
PARP2	0.021	0.077	0.24	62	-10000	0	62
BLM	0.084	0.12	0.24	206	-10000	0	206
Telomerase	-0.016	0.07	0.22	1	-0.32	2	3
IRF1	-0.007	0.056	0.23	15	-0.31	8	23
ESR1	-0.047	0.1	-10000	0	-0.31	75	75
KU/TER	0.003	0.04	0.17	31	-10000	0	31
ATM/TRF2	-0.002	0.029	0.16	18	-10000	0	18
ubiquitin-dependent protein catabolic process	-0.001	0.039	0.18	9	-10000	0	9
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	-0.002	0.04	0.21	2	-10000	0	2
HDAC1	0.009	0.06	0.24	36	-10000	0	36
HDAC2	-0.007	0.038	0.24	11	-0.32	1	12
ATM	0.008	0.036	0.21	18	-10000	0	18
SMAD3	-0.036	0.077	-10000	0	-0.21	91	91
ABL1	-0.008	0.028	-10000	0	-0.31	5	5
MXD1	-0.007	0.021	0.24	4	-10000	0	4
MRE11A	0.025	0.081	0.24	70	-10000	0	70
HUS1	-0.006	0	-10000	0	-10000	0	0
RPS6KB1	-0.001	0.033	0.24	10	-10000	0	10
TERT/NF kappa B1/14-3-3	-0.12	0.18	-10000	0	-0.47	42	42
NR2F2	-0.004	0.039	-10000	0	-0.3	9	9
MAPK3	-0.016	0.032	-10000	0	-0.22	14	14
MAPK1	-0.011	0.013	0.18	1	-0.21	1	2
TGFB1/TGF beta receptor Type II	-0.05	0.11	-10000	0	-0.31	90	90
NFKB1	-0.01	0.033	-10000	0	-0.31	7	7
HNRNPC	-0.006	0	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.008	0.036	0.21	18	-10000	0	18
NBN	0.015	0.071	0.24	49	-0.31	1	50
EGFR	-0.032	0.084	0.24	1	-0.31	46	47
mol:Oestrogen	-0.001	0.003	-10000	0	-10000	0	0
EGF/EGFR	-0.025	0.06	0.16	6	-0.22	46	52
MYC	-0.039	0.092	-10000	0	-0.31	59	59
IL2	-0.012	0.011	-10000	0	-10000	0	0
KU	0.003	0.04	0.17	31	-10000	0	31
RAD50	-0.005	0.019	0.24	2	-0.31	1	3
HSP90AA1	-0.006	0.013	-10000	0	-0.31	1	1
TGFB1	-0.05	0.11	-10000	0	-0.31	90	90
TRF2/BLM	0.051	0.081	0.16	196	-10000	0	196
FRAP1	-0.006	0	-10000	0	-10000	0	0
KU/TERT	-0.12	0.19	-10000	0	-0.48	48	48
SP1/HDAC2	-0.013	0.027	0.17	7	-0.24	1	8
PINX1	-0.002	0.029	0.24	8	-10000	0	8
Telomerase/EST1A	-0.12	0.18	-10000	0	-0.46	60	60
Smad3/Myc	-0.048	0.087	-10000	0	-0.2	131	131
911 complex	0.015	0.029	0.16	23	-10000	0	23
IFNG	0.002	0.055	0.23	30	-0.2	1	31
Telomerase/PinX1	-0.12	0.18	-10000	0	-0.46	60	60
Telomerase/AKT1/mTOR/p70S6K	-0.062	0.12	0.21	1	-0.35	36	37
SIN3B	-0.006	0.011	0.24	1	-10000	0	1
YWHAE	-0.006	0.013	-10000	0	-0.31	1	1
Telomerase/EST1B	-0.12	0.18	-10000	0	-0.46	60	60
response to DNA damage stimulus	0.004	0.018	0.1	18	-10000	0	18
MRN complex/TRF2/Rap1	0.014	0.062	0.15	94	-10000	0	94
TRF2/WRN	0.002	0.041	0.16	35	-10000	0	35
Telomerase/hnRNP C1/C2	-0.12	0.18	-10000	0	-0.46	60	60
E2F1	-0.01	0.007	-10000	0	-10000	0	0
ZNFX1	-0.004	0.025	0.24	6	-10000	0	6
PIF1	-0.006	0	-10000	0	-10000	0	0
NCL	-0.005	0.01	0.24	1	-10000	0	1
DKC1	0.036	0.092	0.24	95	-10000	0	95
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	-0.004	0.021	0.24	4	-10000	0	4
oxygen homeostasis	0	0	-10000	0	-10000	0	0
TCEB2	-0.006	0	-10000	0	-10000	0	0
TCEB1	-0.006	0	-10000	0	-10000	0	0
HIF1A/p53	-0.003	0.027	0.14	1	-0.17	7	8
HIF1A	-0.004	0.02	-10000	0	-0.17	3	3
COPS5	0.014	0.068	0.24	46	-10000	0	46
VHL/Elongin B/Elongin C/RBX1/CUL2	0.039	0.054	0.28	1	-0.15	1	2
FIH (dimer)	-0.006	0	-10000	0	-10000	0	0
CDKN2A	0.13	0.12	0.24	314	-10000	0	314
ARNT/IPAS	-0.005	0.017	0.17	5	-10000	0	5
HIF1AN	-0.006	0	-10000	0	-10000	0	0
GNB2L1	-0.006	0	-10000	0	-10000	0	0
HIF1A/ARNT	-0.002	0.024	0.14	1	-0.16	3	4
CUL2	0.042	0.1	0.24	112	-0.31	1	113
OS9	-0.005	0.01	0.24	1	-10000	0	1
RACK1/Elongin B/Elongin C	0.009	0	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF1A/Hsp90	-0.002	0.023	-10000	0	-0.16	3	3
PHD1-3/OS9	0.017	0.048	0.15	43	-0.16	16	59
HIF1A/RACK1/Elongin B/Elongin C	-0.005	0.023	-10000	0	-10000	0	0
VHL	-0.004	0.018	0.24	3	-10000	0	3
HSP90AA1	-0.006	0.013	-10000	0	-0.31	1	1
HIF1A/JAB1	0.01	0.05	0.16	46	-0.16	3	49
EGLN3	0.004	0.084	0.24	42	-0.31	16	58
EGLN2	-0.006	0	-10000	0	-10000	0	0
EGLN1	-0.006	0	-10000	0	-10000	0	0
TP53	-0.051	0.11	0.24	1	-0.31	85	86
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.024	0.041	-10000	0	-10000	0	0
ARNT	-0.005	0.01	0.24	1	-10000	0	1
ARD1A	-0.001	0.033	0.24	10	-10000	0	10
RBX1	-0.006	0	-10000	0	-10000	0	0
HIF1A/p19ARF	0.08	0.078	0.15	306	-0.16	2	308

×

Regulation 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
HDAC1	0.017	0.075	0.23	57	-10000	0	57
SMARCC1	-0.011	0.027	0.5	1	-10000	0	1
REL	-0.006	0	-10000	0	-10000	0	0
HDAC7	-0.11	0.1	0.22	3	-0.25	139	142
JUN	-0.001	0.042	0.24	14	-0.31	2	16
EP300	-0.007	0.018	-10000	0	-0.31	2	2
KAT2B	0	0	-10000	0	-10000	0	0
KAT5	0	0	-10000	0	-10000	0	0
MAPK14	0.009	0.075	0.19	83	-10000	0	83
FOXO1	-0.009	0.031	-10000	0	-0.31	6	6
T-DHT/AR	-0.11	0.11	0.24	3	-0.26	139	142
MAP2K6	0.021	0.089	0.24	82	-10000	0	82
BRM/BAF57	-0.056	0.087	-10000	0	-0.21	136	136
MAP2K4	-0.018	0.032	-10000	0	-0.31	6	6
SMARCA2	-0.078	0.13	-10000	0	-0.31	136	136
PDE9A	-0.16	0.28	-10000	0	-1	51	51
NCOA2	-0.005	0.015	0.24	2	-10000	0	2
CEBPA	-0.006	0	-10000	0	-10000	0	0
EHMT2	-0.006	0	-10000	0	-10000	0	0
cell proliferation	-0.14	0.12	-10000	0	-0.32	83	83
NR0B1	0.002	0.044	0.24	19	-10000	0	19
EGR1	-0.12	0.15	0.24	3	-0.31	212	215
RXRs/9cRA	0.007	0.034	0.15	13	-0.16	15	28
AR/RACK1/Src	-0.063	0.064	-10000	0	-0.26	4	4
AR/GR	-0.12	0.1	0.15	1	-0.22	280	281
GNB2L1	-0.006	0	-10000	0	-10000	0	0
PKN1	-0.004	0.028	0.24	6	-0.31	1	7
RCHY1	0.004	0.048	0.24	22	-10000	0	22
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
MAPK8	-0.02	0.032	0.18	6	-0.22	6	12
T-DHT/AR/TIF2/CARM1	-0.063	0.069	0.21	2	-0.27	3	5
SRC	-0.02	0.06	0.24	3	-0.2	2	5
NR3C1	-0.011	0.04	-10000	0	-0.31	10	10
KLK3	-0.05	0.062	-10000	0	-0.41	1	1
APPBP2	-0.013	0.028	0.24	5	-0.31	1	6
TRIM24	-0.004	0.023	0.24	5	-10000	0	5
T-DHT/AR/TIP60	-0.063	0.069	0.19	3	-0.2	15	18
TMPRSS2	-0.42	0.46	-10000	0	-0.94	245	245
RXRG	0	0.044	0.24	15	-0.31	2	17
mol:9cRA	0	0	-10000	0	-10000	0	0
RXRA	-0.014	0.048	-10000	0	-0.31	15	15
RXRB	-0.006	0	-10000	0	-10000	0	0
CARM1	-0.005	0.01	0.24	1	-10000	0	1
NR2C2	-0.006	0	-10000	0	-10000	0	0
KLK2	-0.053	0.057	-10000	0	-10000	0	0
AR	-0.12	0.12	0.2	1	-0.24	277	278
SENP1	0.006	0.054	0.24	28	-10000	0	28
HSP90AA1	-0.006	0.013	-10000	0	-0.31	1	1
MDM2	-0.006	0.023	0.24	2	-0.31	2	4
SRY	-0.006	0	-10000	0	-10000	0	0
GATA2	-0.009	0.035	0.24	1	-0.31	7	8
MYST2	-0.006	0.013	-10000	0	-0.31	1	1
HOXB13	-0.005	0.01	0.24	1	-10000	0	1
T-DHT/AR/RACK1/Src	-0.064	0.068	0.2	2	-0.26	4	6
positive regulation of transcription	-0.009	0.035	0.24	1	-0.31	7	8
DNAJA1	-0.014	0.024	0.23	3	-0.32	1	4
proteasomal ubiquitin-dependent protein catabolic process	0.017	0.056	0.27	10	-0.27	2	12
NCOA1	0.004	0.023	0.17	1	-0.34	2	3
SPDEF	-0.022	0.07	0.24	1	-0.31	32	33
T-DHT/AR/TIF2	-0.051	0.055	-10000	0	-0.25	9	9
T-DHT/AR/Hsp90	-0.064	0.071	0.2	3	-0.27	5	8
GSK3B	-0.005	0.008	-10000	0	-10000	0	0
NR2C1	-0.005	0.015	0.24	2	-10000	0	2
mol:T-DHT	-0.019	0.066	0.22	5	-0.19	5	10
SIRT1	-0.006	0	-10000	0	-10000	0	0
ZMIZ2	-0.006	0	-10000	0	-10000	0	0
POU2F1	-0.051	0.05	-10000	0	-0.17	1	1
T-DHT/AR/DAX-1	-0.059	0.077	0.21	7	-0.27	4	11
CREBBP	-0.012	0.042	-10000	0	-0.31	11	11
SMARCE1	-0.006	0	-10000	0	-10000	0	0

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	0.042	0.061	0.19	30	-10000	0	30
ACTA1	0.015	0.067	0.15	39	-0.21	7	46
NUMA1	0.042	0.061	0.19	31	-0.18	1	32
SPTAN1	0.022	0.064	0.16	33	-0.22	5	38
LIMK1	0.023	0.063	0.16	27	-0.22	5	32
BIRC3	-0.047	0.12	0.24	16	-0.31	90	106
BIRC2	0.059	0.11	0.24	149	-10000	0	149
BAX	-0.006	0	-10000	0	-10000	0	0
CASP10	-0.003	0.048	0.17	30	-0.18	13	43
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	0.046	0.062	0.19	30	-10000	0	30
DIABLO	0.077	0.12	0.24	190	-10000	0	190
apoptotic nuclear changes	0.021	0.064	0.16	44	-0.22	5	49
response to UV	0	0	-10000	0	-10000	0	0
CRADD	-0.006	0	-10000	0	-10000	0	0
GSN	0.006	0.076	0.16	23	-0.23	11	34
MADD	-0.006	0	-10000	0	-10000	0	0
TFAP2A	0.038	0.053	-10000	0	-10000	0	0
BID	-0.001	0.031	0.17	2	-0.13	13	15
MAP3K1	0.012	0.05	-10000	0	-0.43	4	4
TRADD	-0.01	0.036	-10000	0	-0.31	8	8
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.003	0.031	0.17	18	-10000	0	18
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	0.013	0.063	0.16	25	-0.21	6	31
CASP9	-0.004	0.011	0.24	1	-10000	0	1
DNA repair	-0.034	0.062	-10000	0	-0.15	97	97
neuron apoptosis	0.008	0.081	-10000	0	-0.6	9	9
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.04	0.065	0.18	39	-0.2	2	41
APAF1	0.002	0.042	0.24	17	-10000	0	17
CASP6	0.048	0.073	-10000	0	-10000	0	0
TRAF2	-0.006	0	-10000	0	-10000	0	0
ICAD/CAD	0.02	0.061	0.17	14	-0.21	5	19
CASP7	0.034	0.086	0.21	92	-0.22	16	108
KRT18	0.018	0.041	-10000	0	-0.52	2	2
apoptosis	0.029	0.084	0.21	31	-0.22	4	35
DFFA	0.023	0.063	0.16	27	-0.22	5	32
DFFB	0.023	0.063	0.16	27	-0.22	5	32
PARP1	0.034	0.062	0.15	96	-10000	0	96
actin filament polymerization	-0.019	0.061	0.21	5	-0.17	15	20
TNF	-0.005	0.01	0.24	1	-10000	0	1
CYCS	-0.001	0.029	0.12	8	-10000	0	8
SATB1	-0.006	0.091	-10000	0	-0.29	1	1
SLK	0.023	0.064	0.17	27	-0.22	5	32
p15 BID/BAX	-0.004	0.026	0.17	1	-10000	0	1
CASP2	-0.028	0.072	-10000	0	-0.34	11	11
JNK cascade	-0.012	0.049	0.43	4	-10000	0	4
CASP3	0.027	0.068	0.17	52	-0.23	5	57
LMNB2	0.013	0.058	0.18	5	-0.25	4	9
RIPK1	-0.006	0	-10000	0	-10000	0	0
CASP4	-0.015	0.055	0.24	2	-0.31	18	20
Mammalian IAPs/DIABLO	0.066	0.12	0.18	240	-0.16	53	293
negative regulation of DNA binding	0.038	0.052	-10000	0	-10000	0	0
stress fiber formation	0.023	0.064	0.17	28	-0.22	5	33
GZMB	-0.002	0.056	0.21	26	-0.21	13	39
CASP1	-0.026	0.1	0.17	19	-0.3	57	76
LMNB1	0.061	0.067	0.18	40	-10000	0	40
APP	0.008	0.082	-10000	0	-0.61	9	9
TNFRSF1A	-0.016	0.054	-10000	0	-0.31	19	19
response to stress	0	0	-10000	0	-10000	0	0
CASP8	-0.004	0	-10000	0	-10000	0	0
VIM	0.032	0.086	0.21	34	-0.22	5	39
LMNA	0.012	0.063	0.18	5	-0.31	5	10
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.031	0.075	-10000	0	-0.35	12	12
LRDD	-0.006	0	-10000	0	-10000	0	0
SREBF1	0.022	0.065	0.16	44	-0.21	7	51
APAF-1/Caspase 9	-0.038	0.12	0.22	2	-0.26	76	78
nuclear fragmentation during apoptosis	0.042	0.061	0.18	31	-0.18	1	32
CFL2	0.019	0.061	0.17	14	-0.21	5	19
GAS2	0.025	0.067	0.17	39	-0.22	5	44
positive regulation of apoptosis	0.038	0.063	0.19	11	-0.24	4	15
PRF1	-0.012	0.046	0.24	1	-0.31	13	14

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.18	0.28	-10000	0	-0.8	60	60
CRP	-0.18	0.28	-10000	0	-0.8	60	60
cell cycle arrest	-0.21	0.34	-10000	0	-0.96	64	64
TIMP1	-0.19	0.3	-10000	0	-0.79	81	81
IL6ST	-0.019	0.05	-10000	0	-0.31	15	15
Rac1/GDP	-0.054	0.096	0.36	1	-0.36	16	17
AP1	-0.023	0.12	0.65	1	-0.51	14	15
GAB2	-0.005	0.061	0.24	15	-0.31	13	28
TNFSF11	-0.18	0.28	-10000	0	-0.8	60	60
HSP90B1	-0.033	0.093	-10000	0	-0.97	4	4
GAB1	-0.006	0.019	-10000	0	-0.31	2	2
MAPK14	-0.008	0.078	0.47	1	-0.46	5	6
AKT1	-0.016	0.088	0.58	1	-0.37	1	2
FOXO1	-0.021	0.086	0.54	1	-0.36	1	2
MAP2K6	-0.016	0.082	0.44	1	-0.36	8	9
mol:GTP	-0.002	0.003	-10000	0	-10000	0	0
MAP2K4	-0.086	0.14	0.44	1	-0.49	11	12
MITF	-0.043	0.083	0.35	1	-0.34	16	17
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	-0.006	0	-10000	0	-10000	0	0
A2M	-0.057	0.26	0.52	3	-1.2	28	31
CEBPB	-0.007	0.028	0.24	1	-0.31	4	5
GRB2/SOS1/GAB family/SHP2	-0.011	0.085	0.27	1	-0.4	12	13
STAT3	-0.23	0.37	-10000	0	-0.98	77	77
STAT1	0.11	0.11	0.28	9	-10000	0	9
CEBPD	-0.23	0.37	-10000	0	-1	86	86
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
PI3K	-0.014	0.12	0.17	98	-0.21	107	205
JUN	-0.001	0.042	0.24	14	-0.31	2	16
PIAS3/MITF	-0.043	0.08	0.32	1	-0.32	16	17
MAPK11	-0.009	0.077	0.47	1	-0.46	5	6
STAT3 (dimer)/FOXO1	-0.18	0.26	-10000	0	-0.7	72	72
GRB2/SOS1/GAB family	-0.019	0.074	0.22	5	-0.28	10	15
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.025	0.064	0.23	2	-0.28	16	18
GRB2	-0.005	0.006	-10000	0	-10000	0	0
JAK2	-0.006	0.023	0.24	2	-0.31	2	4
LBP	-0.14	0.22	0.57	1	-0.67	29	30
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
JAK1	-0.011	0.021	-10000	0	-0.32	2	2
MYC	-0.22	0.36	-10000	0	-0.95	86	86
FGG	-0.18	0.28	-10000	0	-0.81	57	57
macrophage differentiation	-0.21	0.34	-10000	0	-0.96	64	64
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.024	0.056	0.19	3	-0.22	17	20
JUNB	-0.28	0.41	-10000	0	-0.96	138	138
FOS	-0.029	0.11	0.24	26	-0.31	65	91
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.044	0.089	0.39	1	-0.36	16	17
STAT1/PIAS1	-0.046	0.099	-10000	0	-0.37	12	12
GRB2/SOS1/GAB family/SHP2/PI3K	-0.014	0.092	0.5	1	-0.27	10	11
STAT3 (dimer)	-0.23	0.37	-10000	0	-1	70	70
PRKCD	-0.12	0.18	0.5	1	-0.5	50	51
IL6R	-0.01	0.01	-10000	0	-10000	0	0
SOCS3	0.001	0.087	0.52	1	-0.94	2	3
gp130 (dimer)/JAK1/JAK1/LMO4	-0.02	0.046	0.19	2	-0.2	17	19
Rac1/GTP	-0.065	0.11	0.39	1	-0.39	17	18
HCK	-0.005	0.011	0.24	1	-10000	0	1
MAPKKK cascade	-0.018	0.1	0.42	1	-0.54	13	14
bone resorption	-0.17	0.27	-10000	0	-0.75	60	60
IRF1	-0.18	0.3	-10000	0	-0.83	60	60
mol:GDP	-0.047	0.09	0.37	1	-0.35	16	17
SOS1	0.006	0.05	0.24	24	-10000	0	24
VAV1	-0.047	0.091	0.37	1	-0.35	16	17
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.001	0.065	0.42	1	-0.46	5	6
PTPN11	-0.007	0.023	-10000	0	-10000	0	0
IL6/IL6RA	-0.013	0.04	0.17	10	-0.22	9	19
gp130 (dimer)/TYK2/TYK2/LMO4	-0.015	0.04	0.16	6	-0.19	16	22
gp130 (dimer)/JAK2/JAK2/LMO4	-0.015	0.044	0.16	8	-0.2	17	25
IL6	-0.011	0.053	0.24	10	-0.32	9	19
PIAS3	-0.005	0.01	0.24	1	-10000	0	1
PTPRE	0.005	0.019	-10000	0	-10000	0	0
PIAS1	-0.005	0.01	0.24	1	-10000	0	1
RAC1	-0.008	0.013	-10000	0	-0.31	1	1
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.024	0.06	0.21	1	-0.26	17	18
LMO4	-0.007	0.037	0.24	10	-0.31	1	11
STAT3 (dimer)/PIAS3	-0.21	0.33	-10000	0	-0.87	77	77
MCL1	-0.018	0.084	0.68	1	-10000	0	1

×

EPHB forward signaling

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
Ephrin A5/EPHB2	0.009	0.026	0.15	14	-0.18	3	17
cell-cell adhesion	0.02	0.027	-10000	0	-10000	0	0
Ephrin B/EPHB2/RasGAP	0.01	0.047	-10000	0	-0.15	30	30
ITSN1	-0.005	0.01	0.24	1	-10000	0	1
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
SHC1	-0.006	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	0.01	0.028	0.15	19	-0.18	1	20
Ephrin B1/EPHB1	0.009	0.023	0.15	12	-0.18	1	13
HRAS/GDP	-0.022	0.043	-10000	0	-0.2	27	27
Ephrin B/EPHB1/GRB7	0.011	0.049	0.14	31	-0.15	30	61
Endophilin/SYNJ1	-0.011	0.039	0.11	26	-0.14	27	53
KRAS	0.025	0.082	0.24	71	-10000	0	71
Ephrin B/EPHB1/Src	0.011	0.046	0.14	27	-0.15	27	54
endothelial cell migration	-0.005	0.092	0.13	104	-0.16	118	222
GRB2	-0.006	0	-10000	0	-10000	0	0
GRB7	-0.006	0.03	0.24	4	-0.31	3	7
PAK1	-0.008	0.05	0.16	19	-10000	0	19
HRAS	-0.006	0	-10000	0	-10000	0	0
RRAS	-0.024	0.056	-10000	0	-0.15	75	75
DNM1	-0.006	0.013	-10000	0	-0.31	1	1
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.011	0.04	0.11	28	-0.14	27	55
lamellipodium assembly	-0.02	0.027	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.007	0.046	-10000	0	-0.18	23	23
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
EPHB2	-0.001	0.033	0.24	10	-10000	0	10
EPHB3	0.002	0.044	0.24	19	-10000	0	19
EPHB1	-0.001	0.036	0.24	12	-10000	0	12
EPHB4	-0.006	0	-10000	0	-10000	0	0
mol:GDP	-0.015	0.055	0.14	2	-0.22	27	29
Ephrin B/EPHB2	0.008	0.044	0.14	25	-0.15	27	52
Ephrin B/EPHB3	0.01	0.048	0.15	31	-0.15	26	57
JNK cascade	0.004	0.045	0.2	7	-10000	0	7
Ephrin B/EPHB1	0.009	0.045	0.14	27	-0.15	27	54
RAP1/GDP	-0.016	0.053	0.2	2	-0.21	22	24
EFNB2	-0.011	0.073	0.24	16	-0.31	23	39
EFNB3	-0.008	0.025	-10000	0	-0.31	4	4
EFNB1	-0.006	0.013	-10000	0	-0.31	1	1
Ephrin B2/EPHB1-2	0.011	0.051	0.16	36	-0.16	23	59
RAP1B	-0.004	0.023	0.24	5	-10000	0	5
RAP1A	-0.005	0.01	0.24	1	-10000	0	1
CDC42/GTP	-0.019	0.042	-10000	0	-0.18	27	27
Rap1/GTP	-0.022	0.027	-10000	0	-10000	0	0
axon guidance	0.008	0.026	0.15	14	-0.17	3	17
MAPK3	-0.013	0.048	-10000	0	-0.29	3	3
MAPK1	-0.01	0.042	-10000	0	-10000	0	0
Rac1/GDP	-0.016	0.053	-10000	0	-0.22	23	23
actin cytoskeleton reorganization	-0.012	0.025	-10000	0	-0.15	11	11
CDC42/GDP	-0.016	0.053	-10000	0	-0.22	23	23
PI3K	-0.002	0.097	0.14	106	-0.16	118	224
EFNA5	-0.006	0.03	0.24	4	-0.31	3	7
Ephrin B2/EPHB4	0.003	0.044	0.15	16	-0.18	23	39
Ephrin B/EPHB2/Intersectin/N-WASP	-0.007	0.046	-10000	0	-0.18	27	27
CDC42	-0.006	0	-10000	0	-10000	0	0
RAS family/GTP	-0.01	0.02	-10000	0	-10000	0	0
PTK2	0.013	0.081	0.37	28	-10000	0	28
MAP4K4	0.004	0.046	0.21	7	-10000	0	7
SRC	-0.006	0	-10000	0	-10000	0	0
KALRN	-0.004	0.023	0.24	5	-10000	0	5
Intersectin/N-WASP	-0.007	0.007	0.17	1	-10000	0	1
neuron projection morphogenesis	-0.013	0.051	0.2	7	-10000	0	7
MAP2K1	-0.008	0.043	-10000	0	-10000	0	0
WASL	-0.006	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	0.027	0.047	0.16	61	-0.16	1	62
cell migration	-0.013	0.052	-10000	0	-0.21	27	27
NRAS	0.12	0.12	0.24	300	-10000	0	300
SYNJ1	-0.011	0.039	0.11	26	-0.14	27	53
PXN	-0.01	0.033	-10000	0	-0.31	7	7
TF	-0.011	0.04	-10000	0	-10000	0	0
HRAS/GTP	-0.017	0.034	0.1	15	-10000	0	15
Ephrin B1/EPHB1-2	0.013	0.03	0.16	20	-0.16	1	21
cell adhesion mediated by integrin	0.01	0.039	0.16	27	-0.14	13	40
RAC1	-0.006	0.013	-10000	0	-0.31	1	1
mol:GTP	-0.01	0.047	0.14	17	-10000	0	17
RAC1-CDC42/GTP	-0.022	0.027	-10000	0	-10000	0	0
RASA1	-0.007	0.022	-10000	0	-0.31	3	3
RAC1-CDC42/GDP	-0.017	0.051	-10000	0	-0.21	23	23
ruffle organization	-0.016	0.042	0.21	2	-10000	0	2
NCK1	0.012	0.065	0.24	42	-10000	0	42
receptor internalization	-0.013	0.039	0.12	1	-0.27	1	2
Ephrin B/EPHB2/KALRN	0.012	0.047	0.28	1	-0.15	26	27
ROCK1	-0.003	0.026	0.13	20	-0.16	1	21
RAS family/GDP	-0.012	0.027	-10000	0	-0.16	11	11
Rac1/GTP	-0.021	0.029	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src/Paxillin	-0.009	0.051	-10000	0	-0.19	33	33

×

Class I PI3K signaling events

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
ARF5/GTP	0.063	0.07	0.2	54	-10000	0	54
DAPP1	-0.023	0.062	-10000	0	-0.3	1	1
Src family/SYK family/BLNK-LAT/BTK-ITK	0.001	0.072	-10000	0	-0.31	4	4
mol:DAG	0.03	0.067	0.16	51	-0.16	1	52
HRAS	0.005	0.011	-10000	0	-10000	0	0
RAP1A	0.005	0.014	0.23	1	-10000	0	1
ARF5/GDP	0.032	0.035	0.16	2	-10000	0	2
PLCG2	-0.006	0	-10000	0	-10000	0	0
PLCG1	-0.004	0.023	0.24	5	-10000	0	5
ARF5	-0.006	0	-10000	0	-10000	0	0
mol:GTP	0.067	0.073	0.22	54	-10000	0	54
ARF1/GTP	0.059	0.07	0.21	49	-10000	0	49
RHOA	-0.007	0.018	-10000	0	-0.31	2	2
YES1	0.006	0.052	0.24	26	-10000	0	26
RAP1A/GTP	0.066	0.071	0.21	54	-10000	0	54
ADAP1	0.064	0.07	0.21	54	-10000	0	54
ARAP3	0.066	0.072	0.22	54	-10000	0	54
INPPL1	-0.005	0.015	0.24	2	-10000	0	2
PREX1	-0.005	0.01	0.24	1	-10000	0	1
ARHGEF6	-0.003	0.025	0.24	6	-10000	0	6
ARHGEF7	-0.005	0.01	0.24	1	-10000	0	1
ARF1	-0.021	0.066	-10000	0	-0.31	29	29
NRAS	0.12	0.12	0.23	300	-10000	0	300
FYN	-0.047	0.1	0.24	1	-0.31	79	80
ARF6	-0.006	0.013	-10000	0	-0.31	1	1
FGR	-0.006	0	-10000	0	-10000	0	0
mol:Ca2+	0.017	0.038	0.12	17	-10000	0	17
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	-0.005	0.019	0.24	2	-0.31	1	3
ZAP70	-0.006	0	-10000	0	-10000	0	0
mol:IP3	0.02	0.048	0.12	46	-0.12	1	47
LYN	-0.014	0.048	-10000	0	-0.31	15	15
ARF1/GDP	0.03	0.034	0.16	2	-10000	0	2
RhoA/GDP	0.046	0.054	0.15	7	-10000	0	7
PDK1/Src/Hsp90	0.008	0.008	-10000	0	-0.18	1	1
BLNK	-0.014	0.048	-10000	0	-0.31	15	15
actin cytoskeleton reorganization	0.063	0.067	0.19	66	-10000	0	66
SRC	-0.006	0	-10000	0	-10000	0	0
PLEKHA2	-0.005	0.012	0.16	2	-0.18	1	3
RAC1	-0.006	0.013	-10000	0	-0.31	1	1
PTEN	-0.015	0.038	-10000	0	-0.28	11	11
HSP90AA1	-0.006	0.013	-10000	0	-0.31	1	1
ARF6/GTP	0.063	0.07	0.2	54	-0.14	1	55
RhoA/GTP	0.062	0.07	0.2	54	-0.14	1	55
Src family/SYK family/BLNK-LAT	-0.029	0.066	-10000	0	-0.31	4	4
BLK	-0.005	0.01	0.24	1	-10000	0	1
PDPK1	-0.006	0	-10000	0	-10000	0	0
CYTH1	0.064	0.07	0.21	54	-10000	0	54
HCK	-0.005	0.01	0.24	1	-10000	0	1
CYTH3	0.064	0.07	0.21	54	-10000	0	54
CYTH2	0.064	0.07	0.21	54	-10000	0	54
KRAS	0.032	0.076	0.23	71	-10000	0	71
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.042	0.048	0.15	48	-10000	0	48
SGK1	0.033	0.037	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	0.033	0.035	0.17	3	-10000	0	3
SOS1	0.005	0.05	0.24	24	-10000	0	24
SYK	-0.008	0.034	0.24	2	-0.31	6	8
ARF6/GDP	0.063	0.068	0.18	76	-10000	0	76
mol:PI-3-4-5-P3	0.068	0.074	0.22	54	-10000	0	54
ARAP3/RAP1A/GTP	0.066	0.072	0.21	54	-10000	0	54
VAV1	-0.004	0.021	0.24	4	-10000	0	4
mol:PI-3-4-P2	-0.003	0.012	0.2	2	-10000	0	2
RAS family/GTP/PI3K Class I	0.085	0.088	0.15	331	-10000	0	331
PLEKHA1	-0.003	0.022	0.16	10	-10000	0	10
Rac1/GDP	0.032	0.035	0.16	3	-10000	0	3
LAT	-0.006	0	-10000	0	-10000	0	0
Rac1/GTP	0.016	0.029	-10000	0	-10000	0	0
ITK	0.066	0.074	0.21	65	-10000	0	65
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.033	0.08	0.19	49	-0.21	2	51
LCK	-0.006	0	-10000	0	-10000	0	0
BTK	0.068	0.077	0.21	74	-10000	0	74

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	-0.006	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	0.079	0.077	0.21	92	-10000	0	92
NT3 (dimer)/TRKC	0.019	0.063	0.17	82	-10000	0	82
NT3 (dimer)/TRKB	0.03	0.051	0.16	80	-10000	0	80
SHC/Grb2/SOS1/GAB1/PI3K	-0.018	0.096	0.22	8	-10000	0	8
RAPGEF1	-0.006	0	-10000	0	-10000	0	0
BDNF	-0.006	0	-10000	0	-10000	0	0
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
DYNLT1	-0.038	0.093	-10000	0	-0.31	61	61
NTRK1	-0.006	0	-10000	0	-10000	0	0
NTRK2	-0.004	0.018	0.24	3	-10000	0	3
NTRK3	-0.004	0.018	0.24	3	-10000	0	3
NT-4/5 (dimer)/TRKB	0.007	0.012	0.15	4	-10000	0	4
neuron apoptosis	0.019	0.07	0.24	33	-0.17	1	34
SHC 2-3/Grb2	-0.021	0.075	0.18	1	-0.25	33	34
SHC1	-0.006	0	-10000	0	-10000	0	0
SHC2	-0.03	0.1	0.18	1	-0.4	33	34
SHC3	-0.005	0.046	0.18	1	-10000	0	1
STAT3 (dimer)	-0.088	0.13	0.18	1	-0.29	160	161
NT3 (dimer)/TRKA	0.03	0.052	0.16	81	-10000	0	81
RIN/GDP	0.029	0.042	0.17	10	-10000	0	10
GIPC1	-0.002	0.029	0.24	8	-10000	0	8
KRAS	0.025	0.082	0.24	71	-10000	0	71
DNAJA3	-0.012	0.059	0.2	3	-10000	0	3
RIN/GTP	-0.003	0	-10000	0	-10000	0	0
CCND1	-0.16	0.25	0.41	1	-0.56	150	151
MAGED1	-0.007	0.024	0.24	1	-0.31	3	4
PTPN11	-0.006	0	-10000	0	-10000	0	0
RICS	-0.075	0.13	-10000	0	-0.31	130	130
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.015	0.03	0.16	24	-10000	0	24
GRB2	-0.006	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	0.006	0	-10000	0	-10000	0	0
TRKA/NEDD4-2	-0.005	0.024	0.17	9	-0.21	1	10
ELMO1	0.001	0.041	0.24	16	-10000	0	16
RhoG/GTP/ELMO1/DOCK1	0.01	0.027	0.15	17	-0.18	2	19
NGF	0	0	-10000	0	-10000	0	0
HRAS	-0.006	0	-10000	0	-10000	0	0
DOCK1	-0.006	0.021	0.24	1	-0.31	2	3
GAB2	-0.006	0.061	0.24	15	-0.31	13	28
RIT2	-0.006	0	-10000	0	-10000	0	0
RIT1	0.016	0.07	0.24	50	-10000	0	50
FRS2	0.001	0.04	0.24	15	-10000	0	15
DNM1	-0.006	0.013	-10000	0	-0.31	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.005	0.01	0.24	1	-10000	0	1
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.009	0.063	0.18	16	-10000	0	16
mol:GDP	0.038	0.053	0.22	10	-10000	0	10
NGF (dimer)	0	0	-10000	0	-10000	0	0
RhoG/GDP	0.001	0.028	0.17	16	-10000	0	16
RIT1/GDP	0.039	0.054	0.17	43	-10000	0	43
TIAM1	-0.005	0.019	0.24	2	-0.31	1	3
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
BDNF (dimer)/TRKB	0.01	0.011	0.16	3	-10000	0	3
KIDINS220/CRKL/C3G	-0.007	0	-10000	0	-10000	0	0
SHC/RasGAP	-0.008	0.015	-10000	0	-0.21	3	3
FRS2 family/SHP2	0.013	0.024	0.16	15	-10000	0	15
SHC/GRB2/SOS1/GAB1	0.016	0.03	0.15	24	-0.16	2	26
RIT1/GTP	0.012	0.048	0.17	50	-10000	0	50
NT3 (dimer)	0.029	0.086	0.24	80	-10000	0	80
RAP1/GDP	0.002	0.012	-10000	0	-10000	0	0
KIDINS220/CRKL	-0.006	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.006	0	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.008	0.02	0.15	9	-0.17	1	10
Schwann cell development	-0.004	0.007	-10000	0	-10000	0	0
EHD4	-0.006	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.021	0.035	0.15	39	-10000	0	39
FRS2 family/SHP2/CRK family/C3G/GAB2	-0.002	0.033	0.18	2	-10000	0	2
RAP1B	-0.004	0.023	0.24	5	-10000	0	5
RAP1A	-0.005	0.01	0.24	1	-10000	0	1
CDC42/GTP	-0.012	0.005	-10000	0	-10000	0	0
ABL1	-0.008	0.028	-10000	0	-0.31	5	5
SH2B family/GRB2/SOS1	0.001	0.036	0.17	24	-10000	0	24
Rap1/GTP	-0.002	0.021	0.17	4	-10000	0	4
STAT3	-0.088	0.13	0.18	1	-0.29	160	161
axon guidance	-0.011	0.005	-10000	0	-10000	0	0
MAPK3	-0.011	0.024	-10000	0	-0.16	14	14
MAPK1	-0.007	0.009	0.16	1	-0.16	1	2
CDC42/GDP	0.029	0.042	0.17	10	-10000	0	10
NTF3	0.029	0.086	0.24	80	-10000	0	80
NTF4	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/FAIM	0.005	0.011	-10000	0	-0.18	2	2
PI3K	-0.015	0.12	0.17	98	-0.21	107	205
FRS3	-0.006	0	-10000	0	-10000	0	0
FAIM	-0.007	0.018	-10000	0	-0.31	2	2
GAB1	-0.007	0.018	-10000	0	-0.31	2	2
RASGRF1	-0.012	0.059	0.19	2	-10000	0	2
SOS1	0.005	0.05	0.24	24	-10000	0	24
MCF2L	0.015	0.056	0.15	82	-10000	0	82
RGS19	-0.006	0	-10000	0	-10000	0	0
CDC42	-0.006	0	-10000	0	-10000	0	0
RAS family/GTP	0.051	0.068	0.24	21	-10000	0	21
Rac1/GDP	0.029	0.042	0.17	10	-10000	0	10
NGF (dimer)/TRKA/GRIT	-0.035	0.076	-10000	0	-0.18	130	130
neuron projection morphogenesis	-0.083	0.15	-10000	0	-0.48	35	35
NGF (dimer)/TRKA/NEDD4-2	0.008	0.02	0.15	9	-0.18	1	10
MAP2K1	-0.006	0.028	0.15	1	-0.15	2	3
NGFR	-0.005	0.01	0.24	1	-10000	0	1
NGF (dimer)/TRKA/GIPC/GAIP	-0.021	0.058	-10000	0	-0.18	62	62
RAS family/GTP/PI3K	0.057	0.11	0.23	96	-0.18	50	146
FRS2 family/SHP2/GRB2/SOS1	0.022	0.033	-10000	0	-10000	0	0
NRAS	0.12	0.12	0.24	300	-10000	0	300
GRB2/SOS1	0.001	0.036	0.17	24	-10000	0	24
PRKCI	0.1	0.12	0.24	255	-10000	0	255
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	-0.006	0.013	-10000	0	-0.31	1	1
PRKCZ	-0.006	0	-10000	0	-10000	0	0
MAPKKK cascade	0.002	0.038	-10000	0	-0.41	2	2
RASA1	-0.007	0.022	-10000	0	-0.31	3	3
TRKA/c-Abl	-0.009	0.019	-10000	0	-0.21	5	5
SQSTM1	-0.006	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.005	0.058	0.15	11	-0.16	61	72
NGF (dimer)/TRKA/p62/Atypical PKCs	0.069	0.065	-10000	0	-10000	0	0
MATK	-0.006	0	-10000	0	-10000	0	0
NEDD4L	-0.002	0.033	0.24	9	-0.31	1	10
RAS family/GDP	-0.003	0.007	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.011	0.061	0.2	2	-0.15	1	3
Rac1/GTP	-0.011	0.021	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family	0.016	0.023	0.28	1	-10000	0	1

×

LPA4-mediated signaling events

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
ADCY4	-0.005	0.01	0.16	2	-10000	0	2
ADCY5	-0.004	0.014	0.16	4	-10000	0	4
ADCY6	-0.005	0.007	0.16	1	-10000	0	1
ADCY7	-0.005	0.007	0.16	1	-10000	0	1
ADCY1	-0.005	0.007	0.16	1	-10000	0	1
ADCY2	-0.005	0.007	0.16	1	-10000	0	1
ADCY3	-0.005	0.01	0.16	2	-10000	0	2
ADCY8	-0.085	0.09	0.16	10	-0.18	277	287
PRKCE	-0.003	0.008	0.2	1	-10000	0	1
ADCY9	-0.018	0.046	0.16	1	-0.18	44	45
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	-0.048	0.043	0.14	1	-10000	0	1

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.018	0.069	0.27	4	-0.66	1	5
epithelial cell differentiation	-0.02	0.039	-10000	0	-0.63	1	1
ITCH	0.003	0.029	0.22	6	-10000	0	6
WWP1	-0.011	0.081	0.5	3	-1.1	1	4
FYN	-0.047	0.1	0.24	1	-0.31	79	80
EGFR	-0.03	0.083	0.24	1	-0.31	46	47
PRL	-0.005	0.01	0.24	1	-10000	0	1
neuron projection morphogenesis	-0.012	0.063	0.24	4	-0.5	1	5
PTPRZ1	-0.004	0.018	0.24	3	-10000	0	3
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.005	0.064	0.24	1	-0.54	1	2
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	0.003	0.078	0.32	4	-0.6	1	5
ADAM17	0.045	0.093	0.24	103	-10000	0	103
ErbB4/ErbB4	-0.014	0.083	0.46	3	-0.72	1	4
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.13	0.11	0.29	1	-0.29	86	87
NCOR1	-0.007	0.018	-10000	0	-0.31	2	2
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.02	0.089	0.28	4	-0.57	1	5
GRIN2B	-0.021	0.084	0.26	5	-0.54	1	6
ErbB4/ErbB2/betacellulin	0.001	0.075	0.3	4	-0.57	1	5
STAT1	0.13	0.12	0.24	314	-10000	0	314
HBEGF	-0.004	0.018	0.24	3	-10000	0	3
PRLR	0.003	0.046	0.24	20	-10000	0	20
E4ICDs/ETO2	-0.019	0.068	0.3	2	-0.66	1	3
axon guidance	-0.001	0.061	0.34	3	-0.73	1	4
NEDD4	0.001	0.025	0.21	3	-10000	0	3
Prolactin receptor/Prolactin receptor/Prolactin	0	0.033	0.17	21	-10000	0	21
CBFA2T3	-0.006	0	-10000	0	-10000	0	0
ErbB4/ErbB2/HBEGF	0	0.072	0.29	4	-0.57	1	5
MAPK3	-0.01	0.064	0.25	3	-0.51	1	4
STAT1 (dimer)	0.077	0.11	0.25	58	-0.53	1	59
MAPK1	-0.007	0.062	0.24	4	-0.51	1	5
JAK2	-0.006	0.023	0.24	2	-0.31	2	4
ErbB4/ErbB2/neuregulin 1 beta	0.002	0.075	0.29	4	-0.57	1	5
NRG1	0.034	0.077	0.2	102	-10000	0	102
NRG3	-0.23	0.13	0.24	1	-0.31	425	426
NRG2	-0.006	0	-10000	0	-10000	0	0
NRG4	-0.008	0.062	0.24	13	-0.31	15	28
heart development	-0.001	0.061	0.34	3	-0.73	1	4
neural crest cell migration	0.002	0.075	0.28	4	-0.56	1	5
ERBB2	0.034	0.077	0.19	106	-0.22	1	107
WWOX/E4ICDs	-0.019	0.068	0.3	2	-0.66	1	3
SHC1	-0.006	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.032	0.08	0.21	2	-0.29	14	16
apoptosis	0.21	0.16	0.32	366	-0.3	1	367
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.019	0.068	0.3	2	-0.66	1	3
ErbB4/ErbB2/epiregulin	0	0.071	0.29	2	-0.57	1	3
ErbB4/ErbB4/betacellulin/betacellulin	-0.017	0.074	0.28	4	-0.47	2	6
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.003	0.065	-10000	0	-0.58	1	1
MDM2	-0.016	0.07	0.38	2	-0.66	1	3
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	0.006	0.068	0.27	6	-0.53	1	7
STAT5A	-0.005	0.058	0.3	3	-0.7	1	4
ErbB4/EGFR/neuregulin 1 beta	-0.012	0.08	0.28	3	-0.57	1	4
DLG4	-0.006	0	-10000	0	-10000	0	0
GRB2/SHC	-0.007	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.02	0.061	-10000	0	-0.62	1	1
STAT5A (dimer)	-0.01	0.055	-10000	0	-0.69	1	1
MAP3K7IP2	-0.004	0.018	0.24	3	-10000	0	3
STAT5B (dimer)	-0.003	0.058	0.28	3	-0.7	1	4
LRIG1	-0.007	0.053	0.24	10	-0.31	11	21
EREG	-0.005	0.01	0.24	1	-10000	0	1
BTC	-0.004	0.04	0.24	9	-0.31	4	13
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.001	0.061	0.34	3	-0.74	1	4
ERBB4	-0.015	0.082	0.52	2	-0.72	1	3
STAT5B	-0.012	0.042	-10000	0	-0.31	11	11
YAP1	0.005	0.027	-10000	0	-0.51	1	1
GRB2	-0.006	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.001	0.08	0.29	3	-0.57	1	4
glial cell differentiation	0.019	0.061	0.61	1	-10000	0	1
WWOX	-0.006	0	-10000	0	-10000	0	0
cell proliferation	0.004	0.071	0.27	5	-0.58	1	6

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	0.008	0.065	0.17	61	-0.21	12	73
CRKL	0.005	0.054	0.19	1	-0.25	13	14
mol:PIP3	0.008	0.041	0.29	11	-10000	0	11
AKT1	0.001	0.03	0.2	11	-10000	0	11
PTK2B	-0.006	0.013	-10000	0	-0.31	1	1
RAPGEF1	0.002	0.052	0.18	1	-0.36	3	4
RANBP10	-0.006	0.013	-10000	0	-0.31	1	1
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
HGF/MET/SHIP2	0.021	0.055	0.16	63	-0.18	12	75
MAP3K5	0.003	0.051	0.19	2	-0.31	5	7
HGF/MET/CIN85/CBL/ENDOPHILINS	0.023	0.053	0.15	63	-0.16	12	75
AP1	-0.01	0.081	0.2	34	-0.18	59	93
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	-0.006	0	-10000	0	-10000	0	0
apoptosis	-0.063	0.23	0.3	5	-0.69	66	71
STAT3 (dimer)	0.006	0.058	0.21	7	-0.21	19	26
GAB1/CRKL/SHP2/PI3K	-0.002	0.097	0.22	16	-0.34	6	22
INPP5D	0	0	-10000	0	-10000	0	0
CBL/CRK	0.003	0.052	0.18	1	-0.36	3	4
PTPN11	-0.006	0	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	-0.004	0.023	0.24	5	-10000	0	5
PTEN	-0.012	0.042	-10000	0	-0.31	11	11
ELK1	0.015	0.063	0.17	65	-10000	0	65
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.001	0.025	-10000	0	-0.15	1	1
PAK1	0.003	0.035	0.19	11	-10000	0	11
HGF/MET/RANBP10	0.02	0.054	0.16	60	-0.18	12	72
HRAS	0.007	0.089	0.27	2	-0.51	12	14
DOCK1	0.002	0.053	0.18	1	-0.35	4	5
GAB1	0.007	0.057	0.19	2	-0.26	13	15
CRK	0.005	0.054	0.19	1	-0.25	12	13
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	0.01	0.082	0.28	2	-0.45	12	14
JUN	-0.001	0.042	0.24	14	-0.31	2	16
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	0.007	0.048	0.22	2	-0.19	12	14
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
cell morphogenesis	-0.005	0.094	0.2	29	-0.27	14	43
GRB2/SHC	0.012	0.04	0.18	2	-0.17	12	14
FOS	-0.029	0.11	0.24	26	-0.31	65	91
GLMN	0.024	0.051	0.13	102	-10000	0	102
cell motility	0.015	0.063	0.17	65	-10000	0	65
HGF/MET/MUC20	0.018	0.054	0.15	61	-0.18	12	73
cell migration	0.012	0.04	0.17	2	-0.17	12	14
GRB2	-0.006	0	-10000	0	-10000	0	0
CBL	-0.006	0	-10000	0	-10000	0	0
MET/RANBP10	0.007	0.064	0.17	59	-0.21	13	72
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.007	0.058	0.22	7	-0.19	19	26
MET/MUC20	0.01	0.061	0.17	59	-0.21	12	71
RAP1B	0.001	0.05	0.19	2	-0.34	3	5
RAP1A	0.001	0.05	0.17	1	-0.34	3	4
HGF/MET/RANBP9	0.021	0.054	0.16	62	-0.18	12	74
RAF1	0.005	0.085	0.26	2	-0.48	12	14
STAT3	0.006	0.058	0.21	7	-0.21	19	26
cell proliferation	0.001	0.066	0.2	8	-0.31	12	20
RPS6KB1	0.018	0.036	0.16	4	-10000	0	4
MAPK3	0.023	0.11	0.63	15	-10000	0	15
MAPK1	0.008	0.055	0.65	1	-10000	0	1
RANBP9	-0.004	0.018	0.24	3	-10000	0	3
MAPK8	-0.003	0.058	0.19	1	-0.29	4	5
SRC	0.004	0.054	0.2	7	-0.34	1	8
PI3K	0.009	0.1	0.17	98	-0.15	111	209
MET/Glomulin	0.032	0.069	0.2	59	-0.18	9	68
SOS1	0.005	0.05	0.24	24	-10000	0	24
MAP2K1	0.003	0.08	0.25	3	-0.45	12	15
MET	0.014	0.089	0.24	59	-0.31	12	71
MAP4K1	0.005	0.051	0.18	1	-0.36	3	4
PTK2	0.006	0.054	0.24	28	-10000	0	28
MAP2K2	-0.017	0.09	0.25	2	-0.46	12	14
BAD	-0.001	0.028	0.19	11	-10000	0	11
MAP2K4	0	0.05	0.2	1	-0.29	5	6
SHP2/GRB2/SOS1/GAB1	-0.002	0.044	-10000	0	-0.28	13	13
INPPL1	-0.005	0.015	0.24	2	-10000	0	2
PXN	-0.01	0.033	-10000	0	-0.31	7	7
SH3KBP1	-0.005	0.01	0.24	1	-10000	0	1
HGS	0.004	0.044	0.2	2	-0.18	12	14
PLCgamma1/PKC	-0.002	0.016	0.17	5	-10000	0	5
HGF	-0.004	0.021	0.24	4	-10000	0	4
RASA1	-0.007	0.022	-10000	0	-0.31	3	3
NCK1	0.012	0.065	0.24	42	-10000	0	42
PTPRJ	-0.004	0.018	0.24	3	-10000	0	3
NCK/PLCgamma1	0.015	0.06	0.16	49	-0.17	12	61
PDPK1	0.004	0.034	0.23	11	-10000	0	11
HGF/MET/SHIP	0.018	0.054	0.15	61	-0.18	12	73

×

BMP 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
BMP7/BMPR2/BMPR1A-1B/FS	0.007	0.094	0.3	6	-0.17	90	96
SMAD6-7/SMURF1	0.01	0.012	0.16	4	-10000	0	4
NOG	-0.005	0.019	0.24	2	-0.31	1	3
SMAD9	-0.01	0.053	-10000	0	-0.45	6	6
SMAD4	-0.006	0	-10000	0	-10000	0	0
SMAD5	-0.023	0.061	-10000	0	-0.27	4	4
BMP7/USAG1	0.025	0.11	0.18	141	-0.22	41	182
SMAD5/SKI	-0.024	0.059	-10000	0	-0.26	4	4
SMAD1	-0.009	0.027	-10000	0	-0.28	3	3
BMP2	-0.006	0	-10000	0	-10000	0	0
SMAD1/SMAD1/SMAD4	-0.017	0.022	-10000	0	-0.25	3	3
BMPR1A	-0.006	0.033	0.24	4	-0.31	4	8
BMPR1B	-0.034	0.092	0.24	3	-0.31	56	59
BMPR1A-1B/BAMBI	0.003	0.073	0.16	50	-0.18	56	106
AHSG	-0.006	0	-10000	0	-10000	0	0
CER1	-0.005	0.01	0.24	1	-10000	0	1
BMP2-4/CER1	0.012	0.021	0.16	12	-10000	0	12
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.033	0.07	-10000	0	-0.31	7	7
BMP2-4 (homodimer)	-0.004	0.024	0.17	11	-10000	0	11
RGMB	-0.006	0	-10000	0	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.005	0.057	0.15	9	-0.16	61	70
RGMA	-0.013	0.047	-10000	0	-0.31	14	14
SMURF1	-0.006	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.02	0.06	0.19	1	-0.31	3	4
BMP2-4/USAG1	0.038	0.061	0.16	116	-0.18	2	118
SMAD6/SMURF1/SMAD5	-0.024	0.059	-10000	0	-0.26	4	4
SOSTDC1	0.041	0.1	0.24	111	-0.31	2	113
BMP7/BMPR2/BMPR1A-1B	-0.007	0.087	0.15	49	-0.18	92	141
SKI	-0.006	0	-10000	0	-10000	0	0
BMP6 (homodimer)	-0.005	0.015	0.24	2	-10000	0	2
HFE2	-0.006	0	-10000	0	-10000	0	0
ZFYVE16	-0.002	0.029	0.24	8	-10000	0	8
MAP3K7	-0.003	0.025	0.24	6	-10000	0	6
BMP2-4/CHRD	0.012	0.02	0.16	11	-10000	0	11
SMAD5/SMAD5/SMAD4	-0.024	0.059	-10000	0	-0.26	4	4
MAPK1	-0.006	0.016	0.24	1	-0.31	1	2
TAK1/TAB family	-0.023	0.054	-10000	0	-0.27	3	3
BMP7 (homodimer)	-0.01	0.11	0.24	46	-0.31	45	91
NUP214	-0.006	0	-10000	0	-10000	0	0
BMP6/FETUA	-0.006	0.01	0.17	2	-10000	0	2
SMAD1/SKI	-0.01	0.026	-10000	0	-0.27	3	3
SMAD6	-0.004	0.021	0.24	4	-10000	0	4
CTDSP2	-0.007	0.018	-10000	0	-0.31	2	2
BMP2-4/FETUA	0.012	0.02	0.16	11	-10000	0	11
MAP3K7IP1	-0.006	0	-10000	0	-10000	0	0
GREM1	0.004	0.048	0.24	22	-10000	0	22
BMPR2 (homodimer)	-0.006	0.013	-10000	0	-0.31	1	1
GADD34/PP1CA	-0.005	0.055	0.16	7	-0.18	48	55
BMPR1A-1B (homodimer)	-0.026	0.067	0.17	7	-0.21	60	67
CHRDL1	-0.14	0.15	0.24	2	-0.31	263	265
ENDOFIN/SMAD1	-0.008	0.031	-10000	0	-0.27	3	3
SMAD6-7/SMURF1/SMAD1	-0.012	0.027	-10000	0	-0.26	3	3
SMAD6/SMURF1	-0.006	0	-10000	0	-10000	0	0
BAMBI	0.015	0.07	0.24	48	-0.31	1	49
SMURF2	-0.005	0.01	0.24	1	-10000	0	1
BMP2-4/CHRDL1	-0.074	0.096	0.16	7	-0.18	259	266
BMP2-4/GREM1	0.017	0.035	0.16	33	-10000	0	33
SMAD7	-0.006	0	-10000	0	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.007	0.051	-10000	0	-0.43	6	6
SMAD1/SMAD6	-0.01	0.026	-10000	0	-0.27	3	3
TAK1/SMAD6	-0.005	0.018	0.17	6	-10000	0	6
BMP7	-0.01	0.11	0.24	46	-0.31	45	91
BMP6	-0.005	0.015	0.24	2	-10000	0	2
MAP3K7IP2	-0.004	0.018	0.24	3	-10000	0	3
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.018	0.055	0.16	1	-0.29	3	4
PPM1A	-0.006	0	-10000	0	-10000	0	0
SMAD1/SMURF2	-0.01	0.027	-10000	0	-0.27	3	3
SMAD7/SMURF1	-0.007	0	-10000	0	-10000	0	0
CTDSPL	-0.006	0	-10000	0	-10000	0	0
PPP1CA	-0.006	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
CTDSP1	-0.007	0.022	-10000	0	-0.31	3	3
PPP1R15A	-0.032	0.086	0.24	1	-0.31	50	51
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.012	0.07	0.18	6	-0.38	3	9
CHRD	-0.006	0	-10000	0	-10000	0	0
BMPR2	-0.006	0.013	-10000	0	-0.31	1	1
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.021	0.061	0.18	1	-0.32	3	4
BMP4	-0.001	0.034	0.24	11	-10000	0	11
FST	0.017	0.072	0.24	53	-10000	0	53
BMP2-4/NOG	0.012	0.023	0.16	13	-0.18	1	14
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.005	0.083	0.28	1	-0.17	92	93

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	-0.029	0.1	0.17	3	-0.2	104	107
adherens junction organization	-0.016	0.065	0.2	1	-0.27	20	21
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.031	0.089	0.18	3	-0.27	20	23
FMN1	-0.02	0.064	-10000	0	-0.26	22	22
mol:IP3	-0.017	0.084	0.17	2	-0.28	8	10
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.016	0.064	-10000	0	-0.27	20	20
CTNNB1	-0.003	0.016	0.24	2	-10000	0	2
AKT1	-0.019	0.085	0.18	2	-0.3	8	10
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.016	0.059	-10000	0	-0.35	13	13
CTNND1	-0.005	0.007	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.012	0.065	0.17	7	-0.26	19	26
VASP	-0.017	0.061	-10000	0	-0.26	20	20
ZYX	-0.032	0.077	-10000	0	-0.26	30	30
JUB	-0.011	0.068	0.2	3	-0.26	20	23
EGFR(dimer)	-0.026	0.074	0.2	1	-0.27	21	22
E-cadherin/beta catenin-gamma catenin	0	0.039	0.15	2	-0.17	24	26
mol:PI-3-4-5-P3	-0.014	0.094	0.14	94	-0.32	8	102
PIK3CA	0.044	0.1	0.23	122	-10000	0	122
PI3K	-0.014	0.096	0.14	94	-0.32	8	102
FYN	-0.054	0.12	0.16	2	-0.3	74	76
mol:Ca2+	-0.017	0.083	0.17	2	-0.27	8	10
JUP	-0.011	0.046	-10000	0	-0.31	13	13
PIK3R1	-0.073	0.13	-10000	0	-0.31	131	131
mol:DAG	-0.017	0.084	0.17	2	-0.28	8	10
CDH1	-0.011	0.046	-10000	0	-0.31	13	13
RhoA/GDP	-0.032	0.088	0.18	3	-0.27	19	22
establishment of polarity of embryonic epithelium	-0.017	0.06	-10000	0	-0.26	20	20
SRC	-0.006	0	-10000	0	-10000	0	0
RAC1	-0.006	0.013	-10000	0	-0.31	1	1
RHOA	-0.007	0.018	-10000	0	-0.31	2	2
EGFR	-0.03	0.083	0.24	1	-0.31	46	47
CASR	-0.018	0.079	0.16	2	-0.26	8	10
RhoA/GTP	-0.02	0.077	-10000	0	-0.26	8	8
AKT2	-0.018	0.086	0.19	3	-0.3	8	11
actin cable formation	-0.021	0.062	-10000	0	-0.26	20	20
apoptosis	0.024	0.092	0.32	8	-0.18	2	10
CTNNA1	-0.006	0.02	-10000	0	-0.31	2	2
mol:GDP	-0.031	0.092	0.19	3	-0.28	19	22
PIP5K1A	-0.012	0.066	0.17	7	-0.26	19	26
PLCG1	-0.018	0.085	0.17	2	-0.28	8	10
Rac1/GTP	-0.028	0.068	0.17	1	-0.32	10	11
homophilic cell adhesion	-0.001	0.004	-10000	0	-10000	0	0

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	-0.006	0	-10000	0	-10000	0	0
SMAD2	-0.001	0.027	0.17	1	-0.18	3	4
SMAD3	-0.01	0.035	-10000	0	-0.23	4	4
SMAD3/SMAD4	0.1	0.043	0.22	14	-10000	0	14
SMAD4/Ubc9/PIASy	0.009	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.12	0.056	0.23	33	-10000	0	33
PPM1A	-0.006	0	-10000	0	-10000	0	0
CALM1	-0.012	0.042	-10000	0	-0.31	11	11
SMAD2/SMAD4	-0.003	0.023	-10000	0	-0.17	3	3
MAP3K1	-0.008	0.025	-10000	0	-0.31	4	4
TRAP-1/SMAD4	-0.007	0	-10000	0	-10000	0	0
MAPK3	-0.013	0.047	-10000	0	-0.31	14	14
MAPK1	-0.006	0.016	0.24	1	-0.31	1	2
NUP214	-0.006	0	-10000	0	-10000	0	0
CTDSP1	-0.007	0.022	-10000	0	-0.31	3	3
CTDSP2	-0.007	0.018	-10000	0	-0.31	2	2
CTDSPL	-0.006	0	-10000	0	-10000	0	0
KPNB1	-0.006	0	-10000	0	-10000	0	0
TGFBRAP1	-0.006	0	-10000	0	-10000	0	0
UBE2I	-0.006	0	-10000	0	-10000	0	0
NUP153	0.001	0.041	0.24	16	-10000	0	16
KPNA2	0.21	0.081	0.24	500	-10000	0	500
PIAS4	-0.006	0	-10000	0	-10000	0	0

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	-0.005	0.01	0.24	1	-10000	0	1
VLDLR	-0.014	0.055	0.24	3	-0.31	17	20
LRPAP1	-0.006	0.025	0.24	3	-0.31	2	5
NUDC	-0.006	0.013	-10000	0	-0.31	1	1
RELN/LRP8	-0.016	0.081	0.16	28	-0.18	97	125
CaM/Ca2+	-0.007	0.028	-10000	0	-0.21	11	11
KATNA1	-0.006	0	-10000	0	-10000	0	0
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	-0.03	0.07	0.13	29	-0.16	102	131
IQGAP1/CaM	-0.011	0.032	0.17	1	-0.21	13	14
DAB1	-0.006	0	-10000	0	-10000	0	0
IQGAP1	-0.006	0.021	0.24	1	-0.31	2	3
PLA2G7	0.021	0.077	0.24	61	-10000	0	61
CALM1	-0.012	0.042	-10000	0	-0.31	11	11
DYNLT1	-0.038	0.093	-10000	0	-0.31	61	61
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	-0.005	0.025	0.17	9	-0.21	2	11
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	-0.006	0	-10000	0	-10000	0	0
CDK5R1	-0.006	0	-10000	0	-10000	0	0
LIS1/Poliovirus Protein 3A	-0.005	0.009	0.14	2	-10000	0	2
CDK5R2	-0.006	0	-10000	0	-10000	0	0
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.022	0.083	0.16	24	-0.18	112	136
YWHAE	-0.006	0.013	-10000	0	-0.31	1	1
NDEL1/14-3-3 E	-0.016	0.071	0.26	3	-0.25	1	4
MAP1B	-0.024	0.067	0.14	1	-0.22	61	62
RAC1	-0.003	0.016	-10000	0	-0.33	1	1
p35/CDK5	-0.015	0.076	0.28	3	-0.27	1	4
RELN	-0.048	0.13	0.24	22	-0.31	97	119
PAFAH/LIS1	0.011	0.055	0.17	62	-10000	0	62
LIS1/CLIP170	-0.008	0.009	0.14	2	-10000	0	2
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.044	0.051	-10000	0	-0.24	5	5
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.03	0.081	0.2	3	-0.23	15	18
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	-0.015	0.074	0.27	3	-0.26	1	4
LIS1/IQGAP1	-0.008	0.015	0.15	3	-0.18	2	5
RHOA	-0.004	0.021	-10000	0	-0.23	4	4
PAFAH1B1	-0.006	0.012	0.2	2	-10000	0	2
PAFAH1B3	0.004	0.049	0.24	23	-10000	0	23
PAFAH1B2	-0.006	0	-10000	0	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	-0.02	0.044	0.14	3	-0.14	61	64
NDEL1/Katanin 60/Dynein heavy chain	-0.017	0.069	0.24	3	-0.25	1	4
LRP8	-0.003	0.025	0.24	6	-10000	0	6
NDEL1/Katanin 60	-0.016	0.071	0.26	3	-0.25	1	4
P39/CDK5	-0.015	0.076	0.28	3	-0.27	1	4
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	-0.008	0.011	0.14	2	-0.18	1	3
CDK5	-0.014	0.081	0.14	57	-0.15	94	151
PPP2R5D	-0.006	0	-10000	0	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	-0.006	0.008	0.12	2	-10000	0	2
CSNK2A1	-0.006	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.032	0.068	0.15	24	-0.15	110	134
RELN/VLDLR	-0.016	0.08	0.16	29	-0.16	110	139
CDC42	-0.003	0.008	-10000	0	-10000	0	0

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	0	0.043	0.16	3	-0.18	28	31
fibroblast growth factor receptor signaling pathway	0	0.043	0.16	3	-0.18	28	31
LAMA1	0.036	0.093	0.24	96	-10000	0	96
PRNP	-0.011	0.04	-10000	0	-0.31	10	10
GPC1/SLIT2	-0.022	0.07	0.17	18	-0.21	56	74
SMAD2	-0.012	0.021	0.13	1	-0.16	10	11
GPC1/PrPc/Cu2+	0.003	0.024	-10000	0	-0.18	10	10
GPC1/Laminin alpha1	0.023	0.066	0.17	96	-10000	0	96
TDGF1	-0.006	0	-10000	0	-10000	0	0
CRIPTO/GPC1	-0.007	0	-10000	0	-10000	0	0
APP/GPC1	-0.01	0.026	-10000	0	-0.21	9	9
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0	0.036	0.16	26	-10000	0	26
FLT1	-0.006	0	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	0.006	0.023	0.16	1	-0.18	8	9
SERPINC1	-0.006	0	-10000	0	-10000	0	0
FYN	-0.031	0.059	0.16	1	-0.18	79	80
FGR	-0.008	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.021	0.046	-10000	0	-0.22	1	1
SLIT2	-0.028	0.1	0.24	18	-0.31	56	74
GPC1/NRG	-0.007	0.007	0.17	1	-10000	0	1
NRG1	-0.005	0.01	0.24	1	-10000	0	1
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.022	0.041	0.16	49	-10000	0	49
LYN	-0.013	0.027	-10000	0	-0.18	15	15
mol:Spermine	-0.003	0	-10000	0	-10000	0	0
cell growth	0	0.043	0.16	3	-0.18	28	31
BMP signaling pathway	0.006	0	-10000	0	-10000	0	0
SRC	-0.008	0	-10000	0	-10000	0	0
TGFBR1	-0.005	0.01	0.24	1	-10000	0	1
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.13	0.15	0.24	5	-0.31	241	246
GPC1	-0.006	0	-10000	0	-10000	0	0
TGFBR1 (dimer)	-0.005	0.01	0.24	1	-10000	0	1
VEGFA	0.016	0.069	0.24	49	-10000	0	49
BLK	-0.008	0.007	0.16	1	-10000	0	1
HCK	-0.008	0.007	0.16	1	-10000	0	1
FGF2	-0.011	0.04	-10000	0	-0.31	10	10
FGFR1	-0.015	0.057	0.24	3	-0.31	19	22
VEGFR1 homodimer	-0.006	0	-10000	0	-10000	0	0
TGFBR2	-0.01	0.036	-10000	0	-0.31	8	8
cell death	-0.01	0.026	-10000	0	-0.21	9	9
ATIII/GPC1	-0.007	0	-10000	0	-10000	0	0
PLA2G2A/GPC1	-0.092	0.1	0.17	5	-0.21	241	246
LCK	-0.008	0	-10000	0	-10000	0	0
neuron differentiation	-0.007	0.007	0.17	1	-10000	0	1
PrPc/Cu2+	-0.007	0.027	-10000	0	-0.21	10	10
APP	-0.011	0.038	-10000	0	-0.31	9	9
TGFBR2 (dimer)	-0.01	0.036	-10000	0	-0.31	8	8

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.03	0.086	0.28	10	-0.3	7	17
TBX21	-0.12	0.25	0.66	6	-10000	0	6
B2M	-0.009	0.031	-10000	0	-0.31	6	6
TYK2	-0.013	0.029	0.14	2	-10000	0	2
IL12RB1	-0.013	0.029	0.14	1	-10000	0	1
GADD45B	-0.083	0.21	0.61	8	-10000	0	8
IL12RB2	-0.01	0.04	0.24	6	-10000	0	6
GADD45G	-0.095	0.23	0.62	4	-1.1	8	12
natural killer cell activation	-0.008	0.027	0.13	6	-10000	0	6
RELB	-0.007	0.018	-10000	0	-0.31	2	2
RELA	-0.006	0.013	-10000	0	-0.31	1	1
IL18	0.039	0.097	0.24	108	-10000	0	108
IL2RA	-0.003	0.025	0.24	6	-10000	0	6
IFNG	0.006	0.052	0.24	26	-10000	0	26
STAT3 (dimer)	-0.11	0.22	0.53	9	-0.65	9	18
HLA-DRB5	0.03	0.12	0.24	105	-0.31	19	124
FASLG	-0.12	0.25	0.64	8	-0.62	3	11
NF kappa B2 p52/RelB	-0.16	0.2	-10000	0	-0.57	30	30
CD4	-0.001	0.038	0.24	11	-0.31	1	12
SOCS1	-0.012	0.043	-10000	0	-0.31	12	12
EntrezGene:6955	-0.001	0.012	-10000	0	-10000	0	0
CD3D	-0.036	0.095	0.23	3	-0.31	59	62
CD3E	-0.004	0.036	0.23	7	-0.31	3	10
CD3G	0.01	0.062	0.24	37	-10000	0	37
IL12Rbeta2/JAK2	-0.013	0.051	0.19	14	-0.22	2	16
CCL3	-0.12	0.26	0.72	13	-0.62	3	16
CCL4	-0.12	0.25	0.62	10	-0.57	29	39
HLA-A	-0.007	0.018	-10000	0	-0.31	2	2
IL18/IL18R	0.019	0.071	0.31	6	-10000	0	6
NOS2	-0.1	0.23	0.61	10	-0.52	14	24
IL12/IL12R/TYK2/JAK2/SPHK2	-0.026	0.08	0.28	10	-10000	0	10
IL1R1	-0.39	0.54	0.64	5	-1	218	223
IL4	0.007	0.031	-10000	0	-0.15	1	1
JAK2	-0.013	0.037	0.17	5	-0.32	2	7
EntrezGene:6957	0	0.01	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.014	0.067	-10000	0	-0.39	3	3
RAB7A	-0.074	0.2	0.59	4	-0.68	4	8
lysosomal transport	-0.071	0.19	0.59	4	-0.64	4	8
FOS	-0.17	0.41	0.61	17	-1.2	68	85
STAT4 (dimer)	-0.077	0.23	0.6	10	-0.67	4	14
STAT5A (dimer)	-0.15	0.2	0.36	2	-0.56	32	34
GZMA	-0.12	0.26	0.68	8	-0.76	4	12
GZMB	-0.12	0.26	0.69	11	-10000	0	11
HLX	-0.006	0	-10000	0	-10000	0	0
LCK	-0.13	0.26	0.62	10	-0.6	29	39
TCR/CD3/MHC II/CD4	-0.05	0.17	0.29	25	-0.4	68	93
IL2/IL2R	0.011	0.059	0.18	31	-0.17	31	62
MAPK14	-0.085	0.22	0.61	6	-0.75	6	12
CCR5	-0.084	0.2	0.62	4	-10000	0	4
IL1B	0.004	0.072	0.25	40	-10000	0	40
STAT6	-0.044	0.13	0.38	9	-0.69	6	15
STAT4	-0.004	0.018	0.24	3	-10000	0	3
STAT3	-0.011	0.04	-10000	0	-0.31	10	10
STAT1	0.13	0.12	0.24	314	-10000	0	314
NFKB1	-0.01	0.033	-10000	0	-0.31	7	7
NFKB2	-0.006	0	-10000	0	-10000	0	0
IL12B	-0.013	0.03	0.14	3	-10000	0	3
CD8A	-0.006	0	-10000	0	-10000	0	0
CD8B	-0.005	0.018	0.24	3	-10000	0	3
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.03	0.086	0.3	7	-0.28	10	17
IL2RB	-0.006	0.021	0.24	1	-0.31	2	3
proteasomal ubiquitin-dependent protein catabolic process	-0.072	0.22	0.59	10	-0.62	4	14
IL2RG	-0.009	0.09	0.24	30	-0.31	30	60
IL12	-0.009	0.054	0.18	25	-0.22	1	26
STAT5A	-0.01	0.036	-10000	0	-0.31	8	8
CD247	-0.006	0.012	-10000	0	-10000	0	0
IL2	-0.006	0	-10000	0	-10000	0	0
SPHK2	-0.006	0	-10000	0	-10000	0	0
FRAP1	-0.006	0	-10000	0	-10000	0	0
IL12A	-0.002	0.061	0.22	30	-0.32	1	31
IL12/IL12R/TYK2/JAK2	-0.14	0.27	0.7	10	-0.63	29	39
MAP2K3	-0.09	0.22	0.58	8	-0.8	4	12
RIPK2	0.073	0.12	0.24	180	-10000	0	180
MAP2K6	-0.08	0.21	0.59	8	-0.77	4	12
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.074	0.13	-10000	0	-0.31	129	129
IL18RAP	-0.006	0.011	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	-0.015	0.038	0.18	3	-10000	0	3
EOMES	0.006	0.043	-10000	0	-10000	0	0
STAT1 (dimer)	-0.026	0.24	0.59	23	-0.6	2	25
T cell proliferation	-0.053	0.19	0.54	11	-0.55	4	15
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.005	0.015	0.24	1	-10000	0	1
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.11	0.14	0.24	1	-0.56	6	7
ATF2	-0.082	0.2	0.57	6	-0.7	6	12

×

Glucocorticoid receptor regulatory network

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
PCK2	-0.047	0.048	-10000	0	-10000	0	0
SMARCC2	-0.005	0.01	0.24	1	-10000	0	1
SMARCC1	-0.005	0.01	0.24	1	-10000	0	1
TBX21	0.048	0.062	-10000	0	-10000	0	0
SUMO2	-0.009	0.006	-10000	0	-10000	0	0
STAT1 (dimer)	0.13	0.13	0.25	314	-0.17	5	319
FKBP4	0.006	0.054	0.24	28	-10000	0	28
FKBP5	-0.02	0.08	0.24	10	-0.31	34	44
GR alpha/HSP90/FKBP51/HSP90	-0.053	0.067	-10000	0	-0.26	21	21
PRL	0.029	0.051	0.58	1	-10000	0	1
cortisol/GR alpha (dimer)/TIF2	-0.091	0.13	-10000	0	-0.44	18	18
RELA	0.017	0.07	0.23	24	-0.23	3	27
FGG	-0.1	0.12	-10000	0	-0.48	10	10
GR beta/TIF2	-0.053	0.059	-10000	0	-0.24	12	12
IFNG	0.099	0.16	0.52	33	-10000	0	33
apoptosis	-0.15	0.2	-10000	0	-0.53	20	20
CREB1	-0.007	0	-10000	0	-10000	0	0
histone acetylation	0.035	0.067	-10000	0	-10000	0	0
BGLAP	0.046	0.059	0.56	1	-10000	0	1
GR/PKAc	-0.04	0.047	-10000	0	-0.3	1	1
NF kappa B1 p50/RelA	0.035	0.13	0.41	24	-0.28	14	38
SMARCD1	-0.006	0	-10000	0	-10000	0	0
MDM2	-0.032	0.043	-10000	0	-0.23	4	4
GATA3	-0.006	0.015	0.24	2	-10000	0	2
AKT1	-0.005	0.01	0.24	1	-10000	0	1
CSF2	0.023	0.041	-10000	0	-10000	0	0
GSK3B	-0.009	0.006	-10000	0	-10000	0	0
NR1I3	-0.14	0.17	-10000	0	-0.52	2	2
CSN2	-0.092	0.11	-10000	0	-0.4	18	18
BRG1/BAF155/BAF170/BAF60A	0.012	0.018	0.15	6	-0.16	2	8
NFATC1	-0.007	0.013	-10000	0	-0.31	1	1
POU2F1	-0.006	0.007	0.15	1	-10000	0	1
CDKN1A	-0.066	0.22	-10000	0	-1.2	16	16
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.003	0.006	-10000	0	-10000	0	0
SFN	0.003	0.047	0.24	21	-10000	0	21
GR alpha/HSP90/FKBP51/HSP90/14-3-3	-0.044	0.066	-10000	0	-0.25	18	18
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.29	0.36	0.49	2	-0.75	212	214
JUN	0.09	0.14	0.44	38	-10000	0	38
IL4	0.045	0.056	-10000	0	-10000	0	0
CDK5R1	-0.008	0.004	-10000	0	-10000	0	0
PRKACA	-0.006	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.047	0.06	-10000	0	-0.25	16	16
GR alpha/HSP90/FKBP51/HSP90/PP5C	-0.049	0.061	-10000	0	-0.25	18	18
cortisol/GR alpha (monomer)	-0.11	0.15	-10000	0	-0.5	19	19
NCOA2	-0.005	0.015	0.24	2	-10000	0	2
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	0.023	0.13	0.26	53	-0.31	45	98
AP-1/NFAT1-c-4	0.1	0.19	0.54	41	-10000	0	41
AFP	0.058	0.098	0.42	6	-10000	0	6
SUV420H1	-0.005	0.015	0.24	2	-10000	0	2
IRF1	0.026	0.16	0.52	14	-0.76	9	23
TP53	-0.064	0.13	0.24	1	-0.34	99	100
PPP5C	-0.005	0.01	0.24	1	-10000	0	1
KRT17	0.093	0.16	0.6	27	-10000	0	27
KRT14	0.054	0.1	0.58	14	-10000	0	14
TBP	-0.006	0.008	0.19	1	-10000	0	1
CREBBP	-0.015	0.048	-10000	0	-0.26	17	17
HDAC1	0.01	0.06	0.24	36	-10000	0	36
HDAC2	-0.001	0.036	0.24	11	-0.31	1	12
AP-1	0.1	0.19	0.54	41	-10000	0	41
MAPK14	-0.009	0.012	0.24	1	-10000	0	1
MAPK10	-0.018	0.053	0.23	1	-0.31	17	18
MAPK11	-0.009	0.006	-10000	0	-10000	0	0
KRT5	0.14	0.22	0.56	104	-10000	0	104
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
NCOA1	-0.007	0.018	-10000	0	-0.31	2	2
STAT1	0.13	0.13	0.25	314	-0.17	5	319
CGA	0.045	0.055	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	-0.043	0.071	-10000	0	-0.32	9	9
MAPK3	-0.017	0.047	-10000	0	-0.31	14	14
MAPK1	-0.009	0.017	0.23	1	-0.31	1	2
ICAM1	0.097	0.21	0.55	78	-0.85	5	83
NFKB1	0.013	0.077	0.23	24	-0.28	9	33
MAPK8	0.08	0.12	0.38	36	-10000	0	36
MAPK9	-0.009	0.018	0.24	1	-0.31	1	2
cortisol/GR alpha (dimer)	-0.16	0.2	-10000	0	-0.55	21	21
BAX	-0.041	0.11	-10000	0	-10000	0	0
POMC	-0.019	0.12	0.44	1	-10000	0	1
EP300	-0.011	0.031	-10000	0	-0.21	7	7
cortisol/GR alpha (dimer)/p53	-0.13	0.14	-10000	0	-0.5	20	20
proteasomal ubiquitin-dependent protein catabolic process	-0.027	0.04	0.22	3	-0.26	2	5
SGK1	-0.018	0.054	-10000	0	-0.24	27	27
IL13	0.07	0.11	0.5	3	-10000	0	3
IL6	0.057	0.17	0.63	11	-0.86	9	20
PRKACG	-0.006	0	-10000	0	-10000	0	0
IL5	0.054	0.11	-10000	0	-10000	0	0
IL2	0.084	0.14	0.48	21	-10000	0	21
CDK5	0.02	0.079	0.24	65	-10000	0	65
PRKACB	-0.001	0.033	0.24	10	-10000	0	10
HSP90AA1	-0.006	0.013	-10000	0	-0.31	1	1
IL8	0.093	0.18	0.56	60	-10000	0	60
CDK5R1/CDK5	0.01	0.056	0.16	65	-10000	0	65
NF kappa B1 p50/RelA/PKAc	0.029	0.11	0.32	26	-0.24	1	27
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	-0.076	0.13	-10000	0	-0.44	11	11
SMARCA4	-0.005	0.027	0.24	4	-0.31	2	6
chromatin remodeling	-0.063	0.079	-10000	0	-0.32	8	8
NF kappa B1 p50/RelA/Cbp	0.02	0.11	0.35	21	-0.26	1	22
JUN (dimer)	0.09	0.14	0.44	38	-10000	0	38
YWHAH	-0.007	0.022	-10000	0	-0.31	3	3
VIPR1	0.048	0.062	-10000	0	-10000	0	0
NR3C1	-0.079	0.086	-10000	0	-0.33	15	15
NR4A1	-0.12	0.15	0.24	4	-0.31	227	231
TIF2/SUV420H1	-0.006	0.015	0.17	4	-10000	0	4
MAPKKK cascade	-0.15	0.2	-10000	0	-0.53	20	20
cortisol/GR alpha (dimer)/Src-1	-0.093	0.13	-10000	0	-0.44	18	18
PBX1	-0.012	0.042	0.15	1	-0.31	11	12
POU1F1	-0.006	0.007	0.15	1	-10000	0	1
SELE	0.063	0.11	0.46	6	-10000	0	6
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	-0.064	0.08	-10000	0	-0.32	8	8
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	-0.076	0.13	-10000	0	-0.44	11	11
mol:cortisol	-0.068	0.078	-10000	0	-0.26	17	17
MMP1	0.13	0.22	0.54	121	-10000	0	121

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	-0.005	0.01	0.24	1	-10000	0	1
NFATC1	0.057	0.033	-10000	0	-10000	0	0
NFATC2	-0.025	0.041	0.15	4	-0.16	16	20
NFATC3	-0.009	0.02	-10000	0	-10000	0	0
YWHAE	-0.006	0.013	-10000	0	-0.31	1	1
Calcineurin A alpha-beta B1/CABIN1	-0.004	0.033	-10000	0	-0.31	1	1
Exportin 1/Ran/NUP214	0.013	0.043	0.15	46	-10000	0	46
mol:DAG	-0.002	0.003	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.018	0.035	-10000	0	-0.29	1	1
BCL2/BAX	-0.04	0.076	0.17	1	-0.21	93	94
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.013	0.03	-10000	0	-0.22	11	11
CaM/Ca2+	-0.013	0.03	-10000	0	-0.22	11	11
BAX	-0.006	0	-10000	0	-10000	0	0
MAPK14	-0.007	0.011	0.24	1	-10000	0	1
BAD	-0.006	0	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.008	0.031	-10000	0	-0.3	1	1
Calcineurin A alpha-beta B1/BCL2	-0.055	0.11	0.24	1	-0.31	93	94
FKBP8	-0.027	0.077	-10000	0	-0.31	40	40
activation-induced cell death of T cells	0.008	0.031	0.29	1	-10000	0	1
KPNB1	-0.006	0	-10000	0	-10000	0	0
KPNA2	0.21	0.081	0.24	500	-10000	0	500
XPO1	0.014	0.068	0.24	46	-10000	0	46
SFN	0.003	0.047	0.24	21	-10000	0	21
MAP3K8	-0.008	0.004	-10000	0	-10000	0	0
NFAT4/CK1 alpha	-0.019	0.031	-10000	0	-0.19	15	15
MEF2D/NFAT1/Cbp/p300	-0.094	0.11	0.38	4	-0.3	25	29
CABIN1	-0.004	0.033	-10000	0	-0.31	1	1
CALM1	-0.015	0.042	-10000	0	-0.31	11	11
RAN	-0.006	0.001	-10000	0	-10000	0	0
MAP3K1	-0.008	0.025	-10000	0	-0.31	4	4
CAMK4	-0.002	0.031	0.24	9	-10000	0	9
mol:Ca2+	-0.004	0.007	-10000	0	-10000	0	0
MAPK3	-0.013	0.047	-10000	0	-0.31	14	14
YWHAH	-0.007	0.022	-10000	0	-0.31	3	3
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.008	0.003	-10000	0	-10000	0	0
YWHAB	-0.005	0.01	0.24	1	-10000	0	1
MAPK8	-0.005	0.026	0.24	6	-10000	0	6
MAPK9	-0.006	0.016	0.24	1	-0.31	1	2
YWHAG	-0.006	0	-10000	0	-10000	0	0
FKBP1A	-0.006	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.035	0.045	-10000	0	-10000	0	0
PRKCH	-0.007	0.018	-10000	0	-0.31	2	2
CABIN1/Cbp/p300	-0.02	0.032	-10000	0	-0.22	13	13
CASP3	-0.003	0.033	0.24	10	-10000	0	10
PIM1	-0.004	0.018	0.24	3	-10000	0	3
Calcineurin A alpha-beta B1/FKBP12/FK506	-0.005	0.004	-10000	0	-10000	0	0
apoptosis	-0.006	0.042	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	-0.004	0.029	-10000	0	-10000	0	0
PRKCB	0	0	-10000	0	-10000	0	0
PRKCE	-0.005	0.01	0.24	1	-10000	0	1
JNK2/NFAT4	-0.011	0.02	0.16	1	-0.16	1	2
BAD/BCL-XL	-0.007	0.007	0.17	1	-10000	0	1
PRKCD	-0.006	0.021	0.24	1	-0.31	2	3
NUP214	-0.006	0.001	-10000	0	-10000	0	0
PRKCZ	-0.008	0.004	-10000	0	-10000	0	0
PRKCA	-0.005	0.037	0.24	7	-0.31	4	11
PRKCG	-0.006	0	-10000	0	-10000	0	0
PRKCQ	-0.009	0.048	0.24	5	-0.31	11	16
FKBP38/BCL2	-0.054	0.092	0.17	1	-0.22	125	126
EP300	-0.012	0.02	-10000	0	-0.32	2	2
PRKCB1	-0.003	0.025	0.24	6	-10000	0	6
CSNK2A1	-0.006	0	-10000	0	-10000	0	0
NFATc/JNK1	0.054	0.037	0.22	4	-10000	0	4
CaM/Ca2+/FKBP38	-0.025	0.049	-10000	0	-0.18	51	51
FKBP12/FK506	-0.003	0	-10000	0	-10000	0	0
CSNK1A1	-0.014	0.027	0.16	2	-0.18	11	13
CaM/Ca2+/CAMK IV	-0.01	0.03	0.15	8	-0.18	10	18
NFATc/ERK1	0.054	0.035	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.015	0.034	-10000	0	-0.28	1	1
NR4A1	-0.15	0.17	0.49	4	-0.35	228	232
GSK3B	-0.008	0.004	-10000	0	-10000	0	0
positive T cell selection	-0.009	0.02	-10000	0	-10000	0	0
NFAT1/CK1 alpha	-0.028	0.042	0.13	5	-0.22	11	16
RCH1/ KPNB1	0.15	0.058	0.17	500	-10000	0	500
YWHAQ	-0.006	0	-10000	0	-10000	0	0
PRKACA	-0.007	0.003	-10000	0	-10000	0	0
AKAP5	-0.006	0	-10000	0	-10000	0	0
MEF2D	-0.011	0.008	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	-0.006	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.054	0.033	-10000	0	-10000	0	0
CREBBP	-0.017	0.042	-10000	0	-0.31	11	11
BCL2	-0.055	0.11	0.24	1	-0.31	93	94

×

Canonical Wnt signaling pathway

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
HDAC1	0.04	0.077	0.24	54	-10000	0	54
AES	-0.013	0.1	0.15	15	-0.31	54	69
FBXW11	-0.006	0	-10000	0	-10000	0	0
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.006	0.046	0.17	41	-10000	0	41
SMAD4	-0.006	0	-10000	0	-10000	0	0
DKK2	-0.005	0.002	-10000	0	-10000	0	0
TLE1	0.023	0.049	0.19	24	-10000	0	24
MACF1	-0.003	0.028	0.24	6	-0.31	1	7
CTNNB1	0.009	0.04	0.2	5	-10000	0	5
WIF1	0.002	0.033	0.24	10	-10000	0	10
beta catenin/RanBP3	0.12	0.18	0.36	190	-10000	0	190
KREMEN2	-0.005	0.003	-10000	0	-10000	0	0
DKK1	0.002	0.043	0.24	18	-10000	0	18
beta catenin/beta TrCP1	0.021	0.042	0.21	3	-10000	0	3
FZD1	-0.006	0.003	-10000	0	-10000	0	0
AXIN2	-0.073	0.13	0.53	1	-0.67	5	6
AXIN1	-0.004	0.004	-10000	0	-10000	0	0
RAN	-0.001	0.006	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.016	0.026	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	-0.013	0.11	0.25	3	-0.27	42	45
Axin1/APC/GSK3	0.011	0.026	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin/Macf1	0.012	0.036	0.21	2	-10000	0	2
HNF1A	0.022	0.042	0.15	20	-10000	0	20
CTBP1	0.022	0.043	0.16	20	-10000	0	20
MYC	-0.17	0.38	-10000	0	-1.3	59	59
RANBP3	-0.001	0.006	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.02	0.038	0.16	41	-10000	0	41
NKD1	-0.006	0.01	0.24	1	-10000	0	1
TCF4	0.022	0.046	0.16	20	-0.31	1	21
TCF3	0.022	0.042	0.15	20	-10000	0	20
WNT1/LRP6/FZD1/Axin1	0.016	0.039	0.15	41	-10000	0	41
Ran/GTP	0.001	0.006	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.13	0.23	0.47	151	-0.39	2	153
LEF1	0.038	0.079	0.23	59	-0.31	3	62
DVL1	0.017	0.028	0.19	1	-10000	0	1
CSNK2A1	-0.005	0.003	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	-0.1	0.15	-10000	0	-0.43	51	51
DKK1/LRP6/Kremen 2	0.023	0.044	0.16	57	-10000	0	57
LRP6	0.012	0.064	0.24	41	-10000	0	41
CSNK1A1	0.027	0.049	0.18	22	-10000	0	22
NLK	-0.008	0.019	0.24	3	-10000	0	3
CCND1	-0.34	0.54	0.52	1	-1.2	150	151
WNT1	-0.006	0.003	-10000	0	-10000	0	0
GSK3A	-0.006	0.013	-10000	0	-0.31	1	1
GSK3B	-0.006	0.002	-10000	0	-10000	0	0
FRAT1	-0.007	0.013	-10000	0	-0.31	1	1
PPP2R5D	0.012	0.019	-10000	0	-0.22	1	1
APC	-0.002	0.033	0.12	39	-10000	0	39
WNT1/LRP6/FZD1	0.009	0.032	-10000	0	-10000	0	0
CREBBP	0.018	0.052	0.15	20	-0.31	5	25

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.023	0.054	-10000	0	-0.37	7	7
PDGFB-D/PDGFRB/SLAP	-0.009	0.025	0.17	2	-0.21	7	9
PDGFB-D/PDGFRB/APS/CBL	0	0.02	-10000	0	-0.18	7	7
AKT1	-0.068	0.087	-10000	0	-0.26	38	38
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	-0.02	0.052	-10000	0	-0.39	7	7
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
FGR	-0.011	0.031	-10000	0	-0.22	6	6
mol:Ca2+	-0.017	0.053	-10000	0	-0.42	7	7
MYC	-0.088	0.22	-10000	0	-0.73	59	59
SHC1	-0.006	0	-10000	0	-10000	0	0
HRAS/GDP	-0.014	0.018	-10000	0	-0.15	2	2
LRP1/PDGFRB/PDGFB	-0.001	0.03	-10000	0	-0.18	15	15
GRB10	-0.006	0	-10000	0	-10000	0	0
PTPN11	-0.006	0	-10000	0	-10000	0	0
GO:0007205	-0.017	0.053	-10000	0	-0.42	7	7
PTEN	-0.012	0.042	-10000	0	-0.31	11	11
GRB2	-0.006	0	-10000	0	-10000	0	0
GRB7	-0.006	0.03	0.24	4	-0.31	3	7
PDGFB-D/PDGFRB/SHP2	-0.01	0.023	-10000	0	-0.21	7	7
PDGFB-D/PDGFRB/GRB10	-0.01	0.023	-10000	0	-0.21	7	7
cell cycle arrest	-0.009	0.025	0.17	2	-0.21	7	9
HRAS	-0.006	0	-10000	0	-10000	0	0
HIF1A	-0.064	0.08	-10000	0	-0.23	40	40
GAB1	-0.028	0.064	-10000	0	-0.37	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	-0.029	0.062	-10000	0	-0.34	8	8
PDGFB-D/PDGFRB	0.002	0.024	-10000	0	-0.19	7	7
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.005	0.054	0.17	47	-0.21	7	54
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.034	0.065	-10000	0	-0.34	7	7
positive regulation of MAPKKK cascade	-0.01	0.023	-10000	0	-0.21	7	7
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
mol:IP3	-0.018	0.054	-10000	0	-0.42	7	7
E5	-0.001	0.001	-10000	0	-10000	0	0
CSK	-0.004	0.004	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.009	0.031	0.17	4	-0.21	10	14
SHB	-0.006	0	-10000	0	-10000	0	0
BLK	-0.01	0.03	-10000	0	-0.24	1	1
PTPN2	-0.007	0.003	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SNX15	-0.01	0.023	-10000	0	-0.21	7	7
BCAR1	-0.006	0.013	-10000	0	-0.31	1	1
VAV2	-0.039	0.085	-10000	0	-0.34	17	17
CBL	-0.006	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/DEP1	-0.009	0.026	0.17	3	-0.21	7	10
LCK	-0.01	0.03	-10000	0	-0.22	7	7
PDGFRB	-0.01	0.034	-10000	0	-0.31	7	7
ACP1	0.015	0.068	0.24	47	-10000	0	47
HCK	-0.011	0.031	-10000	0	-10000	0	0
ABL1	-0.024	0.053	-10000	0	-0.3	8	8
PDGFB-D/PDGFRB/CBL	-0.028	0.07	-10000	0	-0.46	7	7
PTPN1	-0.007	0.003	-10000	0	-10000	0	0
SNX15	-0.006	0	-10000	0	-10000	0	0
STAT3	-0.011	0.04	-10000	0	-0.31	10	10
STAT1	0.13	0.12	0.24	314	-10000	0	314
cell proliferation	-0.078	0.2	-10000	0	-0.64	59	59
SLA	-0.005	0.015	0.24	2	-10000	0	2
actin cytoskeleton reorganization	-0.009	0.036	-10000	0	-10000	0	0
SRC	-0.01	0.03	-10000	0	-0.24	1	1
PI3K	-0.08	0.08	-10000	0	-0.16	248	248
PDGFB-D/PDGFRB/GRB7/SHC	0.002	0.028	0.16	4	-0.18	10	14
SH2B2	0	0	-10000	0	-10000	0	0
PLCgamma1/SPHK1	-0.02	0.053	-10000	0	-0.4	7	7
LYN	-0.024	0.087	-10000	0	-0.48	17	17
LRP1	-0.01	0.036	-10000	0	-0.31	8	8
SOS1	0.005	0.05	0.24	24	-10000	0	24
STAT5B	-0.012	0.042	-10000	0	-0.31	11	11
STAT5A	-0.01	0.036	-10000	0	-0.31	8	8
NCK1-2/p130 Cas	0.014	0.039	-10000	0	-0.15	2	2
SPHK1	-0.006	0.011	0.24	1	-10000	0	1
EDG1	-0.009	0.031	-10000	0	-0.31	6	6
mol:DAG	-0.018	0.054	-10000	0	-0.42	7	7
PLCG1	-0.018	0.055	-10000	0	-0.43	7	7
NHERF/PDGFRB	-0.064	0.1	-10000	0	-0.21	184	184
YES1	-0.005	0.04	-10000	0	-10000	0	0
cell migration	-0.064	0.1	-10000	0	-0.2	184	184
SHC/Grb2/SOS1	0.011	0.032	-10000	0	-10000	0	0
SLC9A3R2	-0.048	0.1	-10000	0	-0.31	79	79
SLC9A3R1	-0.075	0.13	-10000	0	-0.31	130	130
NHERF1-2/PDGFRB/PTEN	-0.058	0.098	-10000	0	-0.19	193	193
FYN	-0.073	0.16	-10000	0	-0.46	79	79
DOK1	-0.013	0.019	-10000	0	-0.16	9	9
HRAS/GTP	-0.003	0	-10000	0	-10000	0	0
PDGFB	-0.006	0	-10000	0	-10000	0	0
RAC1	-0.059	0.14	-10000	0	-0.43	65	65
PRKCD	-0.014	0.021	0.16	1	-0.17	9	10
FER	-0.013	0.019	0.16	1	-0.17	7	8
MAPKKK cascade	-0.011	0.029	-10000	0	-10000	0	0
RASA1	-0.014	0.021	-10000	0	-0.17	10	10
NCK1	0.012	0.065	0.24	42	-10000	0	42
NCK2	-0.006	0	-10000	0	-10000	0	0
p62DOK/Csk	-0.013	0.018	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SHB	-0.01	0.023	-10000	0	-0.21	7	7
chemotaxis	-0.023	0.052	-10000	0	-0.3	8	8
STAT1-3-5/STAT1-3-5	-0.013	0.028	-10000	0	-0.15	21	21
Bovine Papilomavirus E5/PDGFRB	-0.007	0.023	-10000	0	-0.21	7	7
PTPRJ	-0.004	0.018	0.24	3	-10000	0	3

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	-0.003	0.025	0.18	9	-10000	0	9
RAS family/GTP	0.09	0.11	0.26	101	-0.2	1	102
NFATC4	-0.011	0.044	0.17	8	-10000	0	8
ERBB2IP	-0.005	0.013	-10000	0	-0.3	1	1
HSP90 (dimer)	-0.006	0.013	-10000	0	-0.31	1	1
mammary gland morphogenesis	-0.003	0.066	0.3	8	-0.18	4	12
JUN	0.023	0.11	0.31	51	-10000	0	51
HRAS	-0.004	0.005	-10000	0	-10000	0	0
DOCK7	-0.004	0.059	0.2	14	-0.18	3	17
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.008	0.046	0.14	19	-0.16	26	45
AKT1	-0.003	0.009	0.2	1	-10000	0	1
BAD	-0.005	0.007	0.16	1	-10000	0	1
MAPK10	-0.01	0.038	0.13	11	-0.13	4	15
mol:GTP	0	0.003	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.002	0.071	0.32	8	-0.19	4	12
RAF1	0.075	0.12	0.31	71	-10000	0	71
ErbB2/ErbB3/neuregulin 2	-0.009	0.044	0.15	17	-0.16	27	44
STAT3	-0.011	0.12	-10000	0	-0.9	10	10
cell migration	-0.007	0.041	0.15	11	-0.15	1	12
mol:PI-3-4-5-P3	0	0.001	-10000	0	-10000	0	0
cell proliferation	0.039	0.21	0.56	41	-0.54	4	45
FOS	0.019	0.23	0.52	54	-0.44	63	117
NRAS	0.13	0.12	0.24	300	-10000	0	300
mol:Ca2+	-0.003	0.066	0.3	8	-0.18	4	12
MAPK3	0.041	0.18	0.51	41	-0.48	6	47
MAPK1	0.049	0.18	0.51	42	-0.48	2	44
JAK2	-0.01	0.052	0.19	9	-0.18	4	13
NF2	-0.002	0.009	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.003	0.051	0.15	2	-0.2	24	26
NRG1	-0.004	0.012	0.25	1	-10000	0	1
GRB2/SOS1	0.002	0.036	0.17	24	-10000	0	24
MAPK8	-0.006	0.063	0.23	9	-0.22	21	30
MAPK9	-0.007	0.036	0.14	11	-10000	0	11
ERBB2	-0.003	0.026	0.21	6	-0.21	2	8
ERBB3	-0.012	0.073	0.24	12	-0.31	25	37
SHC1	-0.004	0.006	-10000	0	-10000	0	0
RAC1	-0.006	0.013	-10000	0	-0.31	1	1
apoptosis	0.005	0.01	-10000	0	-0.19	1	1
STAT3 (dimer)	-0.011	0.12	-10000	0	-0.88	10	10
RNF41	-0.005	0.023	0.16	10	-10000	0	10
FRAP1	-0.005	0.007	0.16	1	-10000	0	1
RAC1-CDC42/GTP	-0.019	0.026	-10000	0	-0.13	22	22
ErbB2/ErbB2/HSP90 (dimer)	-0.005	0.021	0.15	6	-0.18	3	9
CHRNA1	0.05	0.17	0.53	42	-0.38	1	43
myelination	-0.013	0.042	0.22	3	-10000	0	3
PPP3CB	-0.01	0.049	0.18	10	-0.17	4	14
KRAS	0.026	0.082	0.24	71	-10000	0	71
RAC1-CDC42/GDP	-0.006	0.045	-10000	0	-0.18	4	4
NRG2	-0.006	0	-10000	0	-10000	0	0
mol:GDP	-0.003	0.051	0.15	2	-0.2	24	26
SOS1	0.006	0.05	0.24	24	-10000	0	24
MAP2K2	0.053	0.12	0.38	39	-0.26	3	42
SRC	-0.006	0	-10000	0	-10000	0	0
mol:cAMP	0	0.001	-10000	0	-10000	0	0
PTPN11	-0.011	0.049	0.18	8	-0.17	4	12
MAP2K1	0.062	0.16	0.48	44	-0.41	2	46
heart morphogenesis	-0.003	0.066	0.3	8	-0.18	4	12
RAS family/GDP	0.094	0.11	0.26	96	-0.19	1	97
GRB2	-0.004	0.005	-10000	0	-10000	0	0
PRKACA	0.001	0.005	-10000	0	-10000	0	0
CHRNE	0.008	0.038	0.26	7	-10000	0	7
HSP90AA1	-0.006	0.013	-10000	0	-0.31	1	1
activation of caspase activity	0.003	0.009	-10000	0	-0.2	1	1
nervous system development	-0.003	0.066	0.3	8	-0.18	4	12
CDC42	-0.006	0	-10000	0	-10000	0	0

×

EGFR-dependent Endothelin 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
HRAS	-0.006	0	-10000	0	-10000	0	0
EGFR	-0.03	0.083	0.24	1	-0.31	46	47
EGF/EGFR	-0.015	0.046	0.12	22	-0.14	47	69
EGF/EGFR dimer/SHC/GRB2/SOS1	0.007	0.054	0.28	2	-0.15	42	44
mol:GTP	0	0	-10000	0	-10000	0	0
EDNRA	-0.004	0.018	0.24	3	-10000	0	3
response to oxidative stress	0	0	-10000	0	-10000	0	0
EGF	-0.003	0.027	0.24	7	-10000	0	7
EGF/EGFR dimer/SHC	-0.005	0.053	0.16	6	-0.18	46	52
mol:GDP	0.005	0.052	0.26	2	-0.15	42	44
mol:Ca2+	0	0	-10000	0	-10000	0	0
EDN1	0	0.04	0.24	14	-0.31	1	15
GRB2/SOS1	0.001	0.036	0.17	24	-10000	0	24
HRAS/GTP	-0.021	0.034	-10000	0	-0.14	42	42
SHC1	-0.006	0	-10000	0	-10000	0	0
HRAS/GDP	-0.022	0.035	-10000	0	-0.14	42	42
FRAP1	-0.017	0.046	0.23	2	-10000	0	2
EGF/EGFR dimer	-0.021	0.061	0.2	7	-0.21	46	53
SOS1	0.005	0.05	0.24	24	-10000	0	24
GRB2	-0.006	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-1	-0.002	0.031	0.17	17	-0.21	1	18

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	-0.001	0.024	-10000	0	-0.29	2	2
HSPA8	-0.007	0.004	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.052	0.074	0.16	1	-0.22	67	68
AKT1	-0.006	0.011	0.24	1	-10000	0	1
GSC	-0.014	0.02	-10000	0	-10000	0	0
NKX2-5	-0.009	0.01	-10000	0	-10000	0	0
muscle cell differentiation	0	0.069	0.38	2	-0.22	4	6
SMAD2-3/SMAD4/SP1	0.027	0.096	0.29	10	-0.32	1	11
SMAD4	-0.003	0.048	0.17	5	-10000	0	5
CBFB	-0.007	0.022	-10000	0	-0.31	3	3
SAP18	-0.007	0.013	-10000	0	-0.31	1	1
Cbp/p300/MSG1	0.016	0.042	0.17	12	-0.17	12	24
SMAD3/SMAD4/VDR	0.003	0.059	0.19	12	-0.21	1	13
MYC	-0.037	0.092	-10000	0	-0.31	59	59
CDKN2B	0.004	0.036	-10000	0	-10000	0	0
AP1	-0.003	0.11	0.45	15	-0.31	4	19
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.054	0.06	0.23	13	-10000	0	13
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.003	0.036	-10000	0	-0.25	1	1
SP3	-0.003	0.019	-10000	0	-10000	0	0
CREB1	-0.006	0	-10000	0	-10000	0	0
FOXH1	-0.009	0.01	-10000	0	-10000	0	0
SMAD3/SMAD4/GR	-0.028	0.053	0.16	2	-0.23	10	12
GATA3	-0.009	0.015	0.24	2	-10000	0	2
SKI/SIN3/HDAC complex/NCoR1	0.003	0.038	0.18	11	-10000	0	11
MEF2C/TIF2	-0.021	0.063	-10000	0	-0.32	20	20
endothelial cell migration	-0.07	0.17	-10000	0	-0.52	68	68
MAX	-0.017	0.03	-10000	0	-0.13	6	6
RBBP7	-0.007	0.018	-10000	0	-0.31	2	2
RBBP4	0.002	0.043	0.24	18	-10000	0	18
RUNX2	-0.004	0.018	0.24	3	-10000	0	3
RUNX3	-0.005	0.01	0.24	1	-10000	0	1
RUNX1	-0.006	0	-10000	0	-10000	0	0
CTBP1	-0.006	0	-10000	0	-10000	0	0
NR3C1	-0.022	0.048	-10000	0	-0.31	10	10
VDR	-0.005	0.01	0.24	1	-10000	0	1
CDKN1A	0.002	0.2	-10000	0	-1.1	16	16
KAT2B	0.001	0.004	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	-0.008	0.036	-10000	0	-10000	0	0
DCP1A	-0.006	0	-10000	0	-10000	0	0
SKI	-0.006	0.001	-10000	0	-10000	0	0
SERPINE1	0.07	0.17	0.52	68	-10000	0	68
SMAD3/SMAD4/ATF2	-0.012	0.042	0.18	8	-0.24	2	10
SMAD3/SMAD4/ATF3	-0.012	0.046	0.19	11	-0.26	3	14
SAP30	-0.006	0.001	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.017	0.045	0.16	1	-0.18	11	12
JUN	-0.003	0.11	0.51	14	-0.33	3	17
SMAD3/SMAD4/IRF7	-0.013	0.045	0.18	10	-0.24	2	12
TFE3	0.009	0.04	0.18	7	-10000	0	7
COL1A2	0.14	0.24	0.47	183	-0.73	6	189
mesenchymal cell differentiation	0.012	0.044	0.24	2	-0.18	10	12
DLX1	-0.005	0.015	0.24	2	-10000	0	2
TCF3	-0.006	0	-10000	0	-10000	0	0
FOS	-0.025	0.11	0.23	26	-0.32	59	85
SMAD3/SMAD4/Max	-0.025	0.048	0.16	2	-0.23	3	5
Cbp/p300/SNIP1	0.009	0.031	0.16	2	-0.17	13	15
ZBTB17	-0.006	0	-10000	0	-10000	0	0
LAMC1	0.031	0.13	0.44	43	-10000	0	43
TGIF2/HDAC complex/SMAD3/SMAD4	-0.013	0.042	0.18	7	-0.23	3	10
IRF7	-0.008	0	-10000	0	-10000	0	0
ESR1	-0.065	0.11	-10000	0	-0.33	74	74
HNF4A	-0.006	0	-10000	0	-10000	0	0
MEF2C	-0.021	0.065	-10000	0	-0.33	20	20
SMAD2-3/SMAD4	-0.015	0.044	0.2	3	-0.24	2	5
Cbp/p300/Src-1	0.011	0.036	-10000	0	-0.17	15	15
IGHV3OR16-13	-0.005	0.008	-10000	0	-10000	0	0
TGIF2/HDAC complex	-0.006	0.013	-10000	0	-0.31	1	1
CREBBP	-0.007	0.044	-10000	0	-0.31	11	11
SKIL	0.14	0.12	0.24	330	-10000	0	330
HDAC1	0.009	0.06	0.24	36	-10000	0	36
HDAC2	-0.002	0.037	0.24	11	-0.31	1	12
SNIP1	-0.006	0.015	0.24	2	-10000	0	2
GCN5L2	-0.001	0.014	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.005	0.071	0.34	9	-0.27	1	10
MSG1/HSC70	-0.004	0.027	0.17	13	-10000	0	13
SMAD2	-0.011	0.02	-10000	0	-0.31	2	2
SMAD3	-0.003	0.051	0.16	7	-0.38	2	9
SMAD3/E2F4-5/DP1/p107/SMAD4	0.024	0.06	0.21	19	-0.25	1	20
SMAD2/SMAD2/SMAD4	0.003	0.032	0.16	1	-10000	0	1
NCOR1	-0.007	0.018	-10000	0	-0.31	2	2
NCOA2	-0.005	0.015	0.24	2	-10000	0	2
NCOA1	-0.007	0.018	-10000	0	-0.31	2	2
MYOD/E2A	-0.007	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.028	0.094	0.28	10	-0.3	1	11
IFNB1	-0.001	0.055	-10000	0	-10000	0	0
SMAD3/SMAD4/MEF2C	-0.017	0.076	-10000	0	-0.34	15	15
CITED1	0	0.037	0.24	13	-10000	0	13
SMAD2-3/SMAD4/ARC105	-0.004	0.055	0.21	4	-0.24	1	5
RBL1	0.015	0.068	0.24	47	-10000	0	47
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.006	0.04	-10000	0	-10000	0	0
RUNX1-3/PEBPB2	0.008	0.015	0.16	1	-0.18	3	4
SMAD7	0.018	0.13	0.46	10	-0.42	1	11
MYC/MIZ-1	-0.028	0.063	-10000	0	-0.21	59	59
SMAD3/SMAD4	0.064	0.1	0.3	60	-10000	0	60
IL10	-0.002	0.055	-10000	0	-10000	0	0
PIASy/HDAC complex	-0.01	0.011	-10000	0	-10000	0	0
PIAS3	-0.003	0.013	0.24	1	-10000	0	1
CDK2	0.097	0.12	0.24	229	-10000	0	229
IL5	-0.002	0.055	-10000	0	-10000	0	0
CDK4	0.001	0.027	0.24	5	-10000	0	5
PIAS4	-0.01	0.011	-10000	0	-10000	0	0
ATF3	-0.002	0.033	0.24	9	-0.31	1	10
SMAD3/SMAD4/SP1	0.025	0.097	0.29	10	-0.27	5	15
FOXG1	-0.005	0.005	-10000	0	-10000	0	0
FOXO3	-0.01	0.026	0.2	1	-0.21	8	9
FOXO1	-0.009	0.023	0.2	1	-0.21	6	7
FOXO4	-0.007	0.009	0.2	1	-10000	0	1
heart looping	-0.021	0.064	-10000	0	-0.33	20	20
CEBPB	-0.008	0.027	0.24	1	-0.31	4	5
SMAD3/SMAD4/DLX1	-0.012	0.042	0.18	8	-0.24	2	10
MYOD1	-0.006	0	-10000	0	-10000	0	0
SMAD3/SMAD4/HNF4	-0.013	0.042	0.18	7	-0.24	2	9
SMAD3/SMAD4/GATA3	-0.009	0.049	0.19	5	-0.27	1	6
SnoN/SIN3/HDAC complex/NCoR1	0.14	0.12	0.24	330	-10000	0	330
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.002	0.053	0.21	5	-0.21	2	7
SMAD3/SMAD4/SP1-3	0.028	0.094	0.28	11	-0.32	1	12
MED15	-0.006	0.013	-10000	0	-0.31	1	1
SP1	0.021	0.053	0.16	10	-10000	0	10
SIN3B	-0.006	0.01	0.24	1	-10000	0	1
SIN3A	-0.006	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.009	0.048	-10000	0	-0.21	14	14
ITGB5	0.034	0.12	0.51	21	-0.29	1	22
TGIF/SIN3/HDAC complex/CtBP	0.006	0.036	0.21	2	-10000	0	2
SMAD3/SMAD4/AR	-0.11	0.097	0.16	1	-0.21	219	220
AR	-0.18	0.15	-10000	0	-0.31	329	329
negative regulation of cell growth	0.021	0.062	0.26	5	-0.28	3	8
SMAD3/SMAD4/MYOD	-0.013	0.042	0.18	7	-0.24	2	9
E2F5	0.014	0.068	0.24	46	-10000	0	46
E2F4	-0.006	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.001	0.041	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4	-0.007	0.041	-10000	0	-0.26	2	2
TFDP1	-0.001	0.034	0.24	11	-10000	0	11
SMAD3/SMAD4/AP1	-0.015	0.08	0.36	3	-0.28	7	10
SMAD3/SMAD4/RUNX2	-0.012	0.044	0.18	10	-0.24	2	12
TGIF2	-0.006	0.013	-10000	0	-0.31	1	1
TGIF1	-0.006	0	-10000	0	-10000	0	0
ATF2	-0.005	0.015	0.24	2	-10000	0	2

×

Wnt signaling

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
Noncanonical Wnts/FZD	0.021	0.055	0.22	10	-0.18	5	15
FZD6	0.008	0.059	0.24	33	-0.31	1	34
WNT6	-0.006	0	-10000	0	-10000	0	0
WNT4	-0.006	0	-10000	0	-10000	0	0
FZD3	0.013	0.074	0.24	48	-0.31	4	52
WNT5A	-0.003	0.025	0.24	6	-10000	0	6
WNT11	0.016	0.07	0.24	50	-10000	0	50

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.012	0.048	-10000	0	-0.17	47	47
ARNO/beta Arrestin1-2	-0.006	0.015	0.13	1	-0.13	7	8
EGFR	-0.03	0.083	0.24	1	-0.31	46	47
EPHA2	-0.005	0.01	0.24	1	-10000	0	1
USP6	-0.006	0	-10000	0	-10000	0	0
IQSEC1	-0.006	0	-10000	0	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.021	0.061	0.2	7	-0.21	46	53
ARRB2	-0.001	0.009	0.16	2	-10000	0	2
mol:GTP	0.004	0.012	0.08	2	-10000	0	2
ARRB1	-0.009	0.035	0.24	1	-0.31	7	8
FBXO8	-0.006	0	-10000	0	-10000	0	0
TSHR	0.001	0.041	0.24	16	-10000	0	16
EGF	-0.003	0.027	0.24	7	-10000	0	7
somatostatin receptor activity	0	0	0	1	-0.001	15	16
ARAP2	0	0	0	1	0	13	14
mol:GDP	-0.013	0.051	-10000	0	-0.22	15	15
mol:PI-3-4-5-P3	0	0	0	1	-0.001	15	16
ITGA2B	-0.006	0	-10000	0	-10000	0	0
ARF6	-0.006	0.013	-10000	0	-0.31	1	1
Ephrin A1/EPHA2/NCK1/GIT1	0.029	0.049	0.16	68	-10000	0	68
ADAP1	0	0	-10000	0	0	10	10
KIF13B	-0.031	0.083	-10000	0	-0.31	47	47
HGF/MET	0.008	0.065	0.17	62	-0.21	12	74
PXN	-0.01	0.033	-10000	0	-0.31	7	7
ARF6/GTP	-0.017	0.054	0.13	1	-0.24	15	16
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.006	0.053	0.16	6	-0.18	46	52
ADRB2	-0.006	0	-10000	0	-10000	0	0
receptor agonist activity	0	0	0	1	0	15	16
actin filament binding	0	0	0	1	0	15	16
SRC	-0.006	0	-10000	0	-10000	0	0
ITGB3	-0.041	0.11	0.24	12	-0.31	77	89
GNAQ	-0.012	0.043	-10000	0	-0.31	12	12
EFA6/PI-4-5-P2	0	0	0.001	3	-0.001	12	15
ARF6/GDP	0.003	0.032	-10000	0	-0.33	1	1
ARF6/GDP/GULP/ACAP1	-0.027	0.068	0.15	2	-0.21	29	31
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.011	0.066	0.15	12	-0.16	81	93
ACAP1	0	0	0	1	-10000	0	1
ACAP2	0	0	0	1	0	13	14
LHCGR/beta Arrestin2	0.004	0.012	0.2	2	-10000	0	2
EFNA1	0.006	0.053	0.24	27	-10000	0	27
HGF	-0.004	0.021	0.24	4	-10000	0	4
CYTH3	0	0	0	1	-0.001	15	16
CYTH2	0	0.001	-10000	0	-0.004	16	16
NCK1	0.012	0.065	0.24	42	-10000	0	42
fibronectin binding	0	0	-10000	0	0	14	14
endosomal lumen acidification	0	0	0	1	0	12	13
microtubule-based process	0	0	-10000	0	-10000	0	0
GULP1	-0.046	0.11	0.24	3	-0.31	78	81
GNAQ/ARNO	0.001	0.003	-10000	0	-10000	0	0
mol:Phosphatidic acid	0	0	0	1	0	13	14
PIP3-E	-0.007	0.018	-10000	0	-0.31	2	2
MET	0.013	0.089	0.24	59	-0.31	12	71
GNA14	-0.005	0.015	0.24	2	-10000	0	2
GNA15	-0.006	0.016	0.24	1	-0.31	1	2
GIT1	-0.005	0.01	0.24	1	-10000	0	1
mol:PI-4-5-P2	0	0	0	1	-0.001	13	14
GNA11	-0.034	0.088	-10000	0	-0.31	53	53
LHCGR	-0.005	0.015	0.24	2	-10000	0	2
AGTR1	-0.006	0	-10000	0	-10000	0	0
desensitization of G-protein coupled receptor protein signaling pathway	0.004	0.012	0.2	2	-10000	0	2
IPCEF1/ARNO	-0.004	0.043	0.16	7	-0.13	48	55
alphaIIb/beta3 Integrin	-0.031	0.076	0.17	12	-0.21	77	89

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.002	0.058	0.25	13	-0.16	18	31
positive regulation of NF-kappaB transcription factor activity	0	0.001	-10000	0	-10000	0	0
CRKL	-0.006	0	-10000	0	-10000	0	0
STAT1 (dimer)/Cbp/p300	0.066	0.12	0.37	32	-0.23	8	40
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.01	0.038	0.14	1	-0.19	18	19
antigen processing and presentation of peptide antigen via MHC class I	-0.034	0.069	0.17	2	-0.23	49	51
CaM/Ca2+	-0.011	0.046	0.26	4	-0.15	25	29
RAP1A	-0.005	0.01	0.24	1	-10000	0	1
STAT1 (dimer)/SHP2	0.076	0.1	0.25	51	-0.26	1	52
AKT1	-0.014	0.09	0.23	14	-0.25	17	31
MAP2K1	-0.009	0.051	0.22	12	-0.23	2	14
MAP3K11	-0.006	0.051	0.23	12	-0.19	4	16
IFNGR1	-0.013	0.05	-10000	0	-0.31	15	15
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.016	0.051	-10000	0	-0.35	8	8
Rap1/GTP	-0.019	0.023	-10000	0	-0.2	2	2
CRKL/C3G	-0.007	0	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.014	0.048	0.23	7	-0.16	18	25
CEBPB	-0.011	0.077	0.35	5	-0.39	5	10
STAT3	-0.011	0.04	-10000	0	-0.31	10	10
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.026	0.15	0.34	1	-1	12	13
STAT1	0.077	0.1	0.25	53	-0.26	1	54
CALM1	-0.011	0.042	-10000	0	-0.31	11	11
IFN-gamma (dimer)	0.004	0.049	0.23	26	-10000	0	26
PIK3CA	0.048	0.1	0.24	122	-10000	0	122
STAT1 (dimer)/PIAS1	0.073	0.099	0.25	48	-0.25	1	49
CEBPB/PTGES2/Cbp/p300	-0.026	0.054	0.41	2	-0.3	6	8
mol:Ca2+	-0.006	0.047	0.28	4	-0.16	18	22
MAPK3	-0.019	0.12	0.32	3	-0.68	14	17
STAT1 (dimer)	-0.033	0.12	0.41	16	-0.36	28	44
MAPK1	-0.003	0.063	0.31	4	-0.71	1	5
JAK2	-0.006	0.025	0.23	2	-0.32	2	4
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
JAK1	-0.007	0.02	-10000	0	-0.31	2	2
CAMK2D	-0.01	0.036	-10000	0	-0.31	8	8
DAPK1	-0.007	0.07	0.36	5	-0.54	3	8
SMAD7	0.016	0.081	0.31	19	-10000	0	19
CBL/CRKL/C3G	-0.012	0.038	0.14	5	-0.22	2	7
PI3K	-0.019	0.083	0.16	3	-0.22	28	31
IFNG	0.004	0.049	0.23	26	-10000	0	26
apoptosis	0.004	0.066	0.37	5	-0.4	3	8
CAMK2G	-0.005	0.002	-10000	0	-10000	0	0
STAT3 (dimer)	-0.011	0.04	-10000	0	-0.31	10	10
CAMK2A	-0.005	0.002	-10000	0	-10000	0	0
CAMK2B	-0.005	0.002	-10000	0	-10000	0	0
FRAP1	-0.014	0.087	0.25	11	-0.24	16	27
PRKCD	-0.014	0.092	0.23	16	-0.25	17	33
RAP1B	-0.004	0.023	0.24	5	-10000	0	5
negative regulation of cell growth	-0.034	0.069	0.17	2	-0.23	49	51
PTPN2	-0.005	0.002	-10000	0	-10000	0	0
EP300	-0.007	0.019	-10000	0	-0.31	2	2
IRF1	0.039	0.13	0.6	15	-0.32	13	28
STAT1 (dimer)/PIASy	0.075	0.1	0.28	40	-0.25	1	41
SOCS1	-0.025	0.17	-10000	0	-1.2	12	12
mol:GDP	-0.014	0.032	-10000	0	-0.22	2	2
CASP1	0.011	0.12	0.46	20	-0.23	50	70
PTGES2	-0.006	0.001	-10000	0	-10000	0	0
IRF9	-0.007	0.047	0.27	8	-0.24	2	10
mol:PI-3-4-5-P3	-0.037	0.062	-10000	0	-0.16	97	97
RAP1/GDP	-0.019	0.024	0.087	1	-0.2	2	3
CBL	-0.006	0.051	0.22	13	-0.18	6	19
MAP3K1	-0.007	0.052	0.23	12	-0.21	3	15
PIAS1	-0.005	0.01	0.24	1	-10000	0	1
PIAS4	-0.005	0.003	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.034	0.069	0.17	2	-0.23	49	51
PTPN11	-0.004	0.053	0.22	15	-0.16	18	33
CREBBP	-0.011	0.042	-10000	0	-0.31	11	11
RAPGEF1	-0.006	0	-10000	0	-10000	0	0

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	-0.013	0.045	-10000	0	-0.19	32	32
epithelial cell differentiation	0.006	0.026	-10000	0	-0.15	15	15
CYFIP2	-0.012	0.042	-10000	0	-0.31	11	11
ENAH	-0.008	0.038	0.17	3	-10000	0	3
EGFR	-0.03	0.083	0.24	1	-0.31	46	47
EPHA2	-0.005	0.01	0.24	1	-10000	0	1
MYO6	-0.012	0.035	0.14	11	-0.28	1	12
CTNNB1	-0.005	0.015	0.24	2	-10000	0	2
ABI1/Sra1/Nap1	0.008	0.032	0.16	10	-0.18	11	21
AQP5	0.019	0.062	-10000	0	-10000	0	0
CTNND1	-0.006	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.013	0.022	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.015	0.026	-10000	0	-10000	0	0
EGF	-0.003	0.027	0.24	7	-10000	0	7
NCKAP1	-0.002	0.031	0.24	9	-10000	0	9
AQP3	-0.12	0.17	-10000	0	-0.39	160	160
cortical microtubule organization	0.006	0.026	-10000	0	-0.15	15	15
GO:0000145	-0.013	0.021	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.006	0.027	-10000	0	-0.15	15	15
MLLT4	-0.021	0.066	-10000	0	-0.31	29	29
ARF6/GDP	-0.018	0.02	-10000	0	-10000	0	0
ARF6	-0.006	0.013	-10000	0	-0.31	1	1
Ephrin A1/EPHA2/NCK1/GIT1	0.029	0.049	0.16	68	-10000	0	68
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.04	0.077	-10000	0	-0.22	74	74
PVRL2	-0.006	0.016	0.24	1	-0.31	1	2
ZYX	-0.031	0.051	-10000	0	-0.28	2	2
ARF6/GTP	0.027	0.043	0.26	3	-0.15	1	4
CDH1	-0.013	0.045	-10000	0	-0.31	13	13
EGFR/EGFR/EGF/EGF	-0.026	0.042	-10000	0	-0.15	59	59
RhoA/GDP	-0.014	0.023	-10000	0	-0.14	17	17
actin cytoskeleton organization	-0.013	0.033	-10000	0	-0.27	1	1
IGF-1R heterotetramer	-0.07	0.12	-10000	0	-0.31	121	121
GIT1	-0.005	0.01	0.24	1	-10000	0	1
IGF1R	-0.07	0.12	-10000	0	-0.31	121	121
IGF1	-0.016	0.06	0.24	3	-0.31	21	24
DIAPH1	-0.003	0.08	-10000	0	-0.53	12	12
Wnt receptor signaling pathway	-0.006	0.026	0.15	15	-10000	0	15
RHOA	-0.007	0.018	-10000	0	-0.31	2	2
RhoA/GTP	-0.018	0.021	-10000	0	-10000	0	0
CTNNA1	-0.007	0.018	-10000	0	-0.31	2	2
VCL	-0.013	0.033	-10000	0	-0.28	1	1
EFNA1	0.006	0.053	0.24	27	-10000	0	27
LPP	-0.019	0.034	-10000	0	-0.33	2	2
Ephrin A1/EPHA2	-0.015	0.02	-10000	0	-0.14	14	14
SEC6/SEC8	-0.024	0.035	-10000	0	-0.26	4	4
MGAT3	-0.015	0.026	-10000	0	-10000	0	0
HGF/MET	-0.017	0.028	-10000	0	-0.14	26	26
HGF	-0.004	0.021	0.24	4	-10000	0	4
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.013	0.045	-10000	0	-0.19	32	32
actin cable formation	-0.022	0.057	0.15	3	-0.22	12	15
KIAA1543	-0.015	0.026	-10000	0	-0.39	1	1
KIFC3	-0.014	0.023	-10000	0	-10000	0	0
NCK1	0.012	0.065	0.24	42	-10000	0	42
EXOC3	-0.005	0.01	0.24	1	-10000	0	1
ACTN1	-0.016	0.031	-10000	0	-0.28	2	2
NCK1/GIT1	0.006	0.047	0.17	43	-10000	0	43
mol:GDP	0.006	0.026	-10000	0	-0.15	15	15
EXOC4	-0.004	0.021	0.24	4	-10000	0	4
STX4	-0.014	0.023	-10000	0	-10000	0	0
PIP5K1C	-0.014	0.023	-10000	0	-10000	0	0
LIMA1	-0.015	0.053	-10000	0	-0.31	18	18
ABI1	-0.005	0.01	0.24	1	-10000	0	1
ROCK1	-0.007	0.041	0.18	3	-10000	0	3
adherens junction assembly	-0.013	0.031	-10000	0	-0.55	1	1
IGF-1R heterotetramer/IGF1	-0.048	0.061	-10000	0	-0.15	151	151
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.017	0.046	0.17	1	-0.21	30	31
MET	0.014	0.089	0.24	59	-0.31	12	71
PLEKHA7	-0.014	0.025	-10000	0	-0.15	15	15
mol:GTP	0.028	0.047	0.15	68	-10000	0	68
establishment of epithelial cell apical/basal polarity	-0.025	0.036	-10000	0	-0.25	4	4
cortical actin cytoskeleton stabilization	-0.013	0.045	-10000	0	-0.19	32	32
regulation of cell-cell adhesion	-0.013	0.033	-10000	0	-0.27	1	1
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.013	0.045	-10000	0	-0.19	32	32

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	-0.003	0.025	0.24	6	-10000	0	6
ITGB7	-0.006	0.016	0.24	1	-0.31	1	2
ITGA4	0.007	0.055	0.24	30	-10000	0	30
alpha4/beta7 Integrin	0.002	0.043	0.18	30	-0.21	1	31
alpha4/beta1 Integrin	0.004	0.046	0.18	34	-10000	0	34

×

Presenilin action in Notch and Wnt 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
Delta 1/NOTCH/NOTCH(cleaved)	-0.01	0.078	-10000	0	-0.5	13	13
HDAC1	0.025	0.064	0.26	36	-10000	0	36
AES	-0.046	0.11	-10000	0	-0.3	89	89
FBXW11	-0.006	0	-10000	0	-10000	0	0
DTX1	-0.006	0	-10000	0	-10000	0	0
LRP6/FZD1	0.005	0.046	0.17	41	-10000	0	41
TLE1	0.002	0.03	0.25	6	-0.3	1	7
AP1	-0.017	0.08	0.23	6	-0.2	70	76
NCSTN	-0.006	0.01	0.24	1	-10000	0	1
ADAM10	-0.001	0.015	0.24	2	-10000	0	2
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.12	0.17	-10000	0	-0.52	46	46
NICD/RBPSUH	-0.011	0.078	-10000	0	-0.5	13	13
WIF1	-0.002	0.033	0.24	10	-10000	0	10
NOTCH1	-0.014	0.081	-10000	0	-0.53	13	13
PSENEN	-0.016	0.054	-10000	0	-0.31	19	19
KREMEN2	-0.006	0	-10000	0	-10000	0	0
DKK1	0.002	0.043	0.24	18	-10000	0	18
beta catenin/beta TrCP1	-0.025	0.037	-10000	0	-10000	0	0
APH1B	-0.039	0.093	-10000	0	-0.31	61	61
APH1A	-0.006	0.01	0.24	1	-10000	0	1
AXIN1	-0.004	0.027	-10000	0	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	0.023	0.099	0.25	32	-10000	0	32
PSEN1	-0.006	0.01	0.24	1	-10000	0	1
FOS	-0.029	0.11	0.24	26	-0.31	65	91
JUN	-0.001	0.042	0.24	14	-0.31	2	16
MAP3K7	0.005	0.027	0.24	6	-10000	0	6
CTNNB1	-0.024	0.038	-10000	0	-10000	0	0
MAPK3	-0.013	0.047	-10000	0	-0.31	14	14
DKK2/LRP6/Kremen 2	0.014	0.04	0.16	41	-10000	0	41
HNF1A	0.002	0.012	-10000	0	-10000	0	0
CTBP1	0.002	0.012	-10000	0	-10000	0	0
MYC	-0.14	0.36	-10000	0	-1.2	59	59
NKD1	-0.001	0.012	0.24	1	-10000	0	1
FZD1	-0.006	0.001	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.012	0.077	-10000	0	-0.5	13	13
apoptosis	-0.017	0.08	0.23	6	-0.2	70	76
Delta 1/NOTCHprecursor	-0.012	0.077	-10000	0	-0.5	13	13
DLL1	-0.006	0	-10000	0	-10000	0	0
PPARD	-0.03	0.042	-10000	0	-10000	0	0
Gamma Secretase	-0.019	0.058	-10000	0	-0.16	78	78
APC	-0.004	0.027	-10000	0	-10000	0	0
DVL1	-0.006	0.011	-10000	0	-10000	0	0
CSNK2A1	-0.007	0.002	-10000	0	-10000	0	0
MAP3K7IP1	0.003	0.012	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	0.018	0.047	0.16	57	-10000	0	57
LRP6	0.012	0.064	0.24	41	-10000	0	41
CSNK1A1	-0.006	0.015	0.24	2	-10000	0	2
NLK	0.013	0.027	0.16	9	-10000	0	9
CCND1	-0.32	0.52	0.52	1	-1.2	150	151
WNT1	-0.006	0.001	-10000	0	-10000	0	0
Axin1/APC/beta catenin	-0.027	0.041	-10000	0	-10000	0	0
DKK2	-0.006	0	-10000	0	-10000	0	0
NOTCH1 precursor/DVL1	-0.017	0.071	-10000	0	-0.46	13	13
GSK3B	-0.001	0.006	-10000	0	-10000	0	0
FRAT1	-0.001	0.015	-10000	0	-0.31	1	1
NOTCH/Deltex homolog 1	-0.01	0.078	-10000	0	-0.5	13	13
PPP2R5D	-0.003	0.01	-10000	0	-10000	0	0
MAPK1	-0.006	0.016	0.24	1	-0.31	1	2
WNT1/LRP6/FZD1	0.016	0.046	0.16	48	-10000	0	48
RBPJ	-0.005	0.01	0.24	1	-10000	0	1
CREBBP	-0.009	0.04	-10000	0	-0.3	11	11

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.019	0.071	0.2	2	-0.32	12	14
FYN	-0.038	0.11	0.3	10	-0.36	32	42
LAT/GRAP2/SLP76	-0.029	0.073	-10000	0	-0.34	16	16
IKBKB	-0.005	0.015	0.24	2	-10000	0	2
AKT1	-0.019	0.078	0.24	10	-0.31	16	26
B2M	-0.008	0.032	-10000	0	-0.31	6	6
IKBKG	-0.01	0.024	-10000	0	-0.11	8	8
MAP3K8	-0.006	0	-10000	0	-10000	0	0
mol:Ca2+	-0.01	0.008	-10000	0	-0.041	12	12
integrin-mediated signaling pathway	0.006	0.006	0.15	1	-10000	0	1
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.025	0.1	0.27	10	-0.42	16	26
TRPV6	0.003	0.027	0.48	1	-10000	0	1
CD28	-0.005	0.004	-10000	0	-10000	0	0
SHC1	-0.019	0.087	0.3	7	-0.38	12	19
receptor internalization	-0.015	0.078	0.28	7	-0.33	12	19
PRF1	-0.034	0.17	0.67	1	-1	14	15
KRAS	0.025	0.082	0.24	71	-10000	0	71
GRB2	-0.006	0	-10000	0	-10000	0	0
COT/AKT1	-0.017	0.065	0.21	10	-0.25	16	26
LAT	-0.019	0.086	0.3	7	-0.38	12	19
EntrezGene:6955	-0.001	0.004	0.051	1	-10000	0	1
CD3D	-0.035	0.096	0.25	3	-0.31	59	62
CD3E	-0.004	0.037	0.25	7	-0.32	3	10
CD3G	0.01	0.061	0.24	37	-10000	0	37
RASGRP2	-0.003	0.009	0.064	1	-10000	0	1
RASGRP1	-0.049	0.12	0.26	7	-0.29	83	90
HLA-A	-0.007	0.019	-10000	0	-0.32	2	2
RASSF5	-0.006	0	-10000	0	-10000	0	0
RAP1A/GTP/RAPL	0.006	0.006	0.15	1	-10000	0	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	-0.009	0.039	0.12	11	-0.1	25	36
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.02	0.032	-10000	0	-0.16	15	15
PRKCA	-0.018	0.042	0.11	5	-0.18	17	22
GRAP2	-0.006	0	-10000	0	-10000	0	0
mol:IP3	-0.026	0.055	-10000	0	-0.27	15	15
EntrezGene:6957	-0.001	0.004	0.058	1	-10000	0	1
TCR/CD3/MHC I/CD8	-0.016	0.076	0.26	7	-0.34	12	19
ORAI1	-0.015	0.049	-10000	0	-0.38	1	1
CSK	-0.02	0.086	0.3	7	-0.39	12	19
B7 family/CD28	-0.021	0.1	0.37	10	-0.38	18	28
CHUK	0.002	0.043	0.24	18	-10000	0	18
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.022	0.091	0.31	7	-0.42	12	19
PTPN6	-0.02	0.09	0.27	10	-0.4	12	22
VAV1	-0.019	0.087	0.3	7	-0.38	12	19
Monovalent TCR/CD3	-0.015	0.076	0.29	7	-0.2	56	63
CBL	-0.006	0	-10000	0	-10000	0	0
LCK	-0.022	0.1	0.29	10	-0.37	23	33
PAG1	-0.019	0.086	0.3	7	-0.39	12	19
RAP1A	-0.005	0.01	0.24	1	-10000	0	1
TCR/CD3/MHC I/CD8/LCK	-0.022	0.092	0.32	7	-0.43	12	19
CD80	-0.001	0.034	0.24	11	-10000	0	11
CD86	0.002	0.043	0.24	18	-10000	0	18
PDK1/CARD11/BCL10/MALT1	-0.021	0.039	-10000	0	-0.19	15	15
HRAS	-0.006	0	-10000	0	-10000	0	0
GO:0035030	-0.019	0.09	0.32	11	-0.33	18	29
CD8A	-0.005	0.006	-10000	0	-10000	0	0
CD8B	-0.004	0.018	0.23	3	-10000	0	3
PTPRC	-0.005	0.11	0.24	53	-0.31	41	94
PDK1/PKC theta	-0.025	0.088	0.26	10	-0.35	17	27
CSK/PAG1	-0.021	0.083	0.28	7	-0.38	12	19
SOS1	0.005	0.05	0.24	24	-10000	0	24
peptide-MHC class I	-0.009	0.027	-10000	0	-0.22	8	8
GRAP2/SLP76	-0.029	0.082	-10000	0	-0.39	16	16
STIM1	-0.02	0.07	-10000	0	-0.3	32	32
RAS family/GTP	0.031	0.064	0.15	58	-0.14	5	63
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.016	0.08	0.28	7	-0.35	12	19
mol:DAG	-0.026	0.049	-10000	0	-0.25	15	15
RAP1A/GDP	-0.005	0.018	0.071	5	-0.053	8	13
PLCG1	-0.004	0.023	0.24	5	-10000	0	5
CD247	-0.006	0.005	-10000	0	-10000	0	0
cytotoxic T cell degranulation	-0.032	0.16	0.67	1	-0.96	14	15
RAP1A/GTP	-0.002	0.003	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.021	0.088	0.26	10	-0.36	16	26
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.031	0.067	-10000	0	-0.33	15	15
NRAS	0.12	0.12	0.24	300	-10000	0	300
ZAP70	-0.006	0.002	-10000	0	-10000	0	0
GRB2/SOS1	0.001	0.036	0.17	24	-10000	0	24
LAT/GRAP2/SLP76/VAV1	-0.032	0.067	-10000	0	-0.33	16	16
MALT1	0.011	0.062	0.24	38	-10000	0	38
TRAF6	-0.005	0.015	0.24	2	-10000	0	2
CD8 heterodimer	-0.005	0.014	0.15	3	-10000	0	3
CARD11	-0.005	0.01	0.24	1	-10000	0	1
PRKCB	-0.02	0.035	-10000	0	-0.18	15	15
PRKCE	-0.019	0.038	-10000	0	-0.18	15	15
PRKCQ	-0.026	0.095	0.26	10	-0.39	17	27
LCP2	-0.015	0.053	-10000	0	-0.31	18	18
BCL10	-0.006	0	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.016	0.07	0.23	10	-0.27	16	26
IKK complex	-0.003	0.027	0.11	12	-0.093	5	17
RAS family/GDP	-0.002	0.006	-10000	0	-0.035	2	2
MAP3K14	-0.015	0.053	0.2	8	-0.2	16	24
PDPK1	-0.019	0.075	0.24	10	-0.3	16	26
TCR/CD3/MHC I/CD8/Fyn	-0.023	0.094	0.3	7	-0.42	14	21

×

Atypical NF-kappaB pathway

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
BCL3/RelA	-0.008	0.02	-10000	0	-0.27	3	3
FBXW11	-0.006	0	-10000	0	-10000	0	0
NF kappa B1 p50/c-Rel	-0.01	0.021	0.14	2	-0.18	7	9
NF kappa B1 p50/RelA/I kappa B alpha	-0.014	0.033	-10000	0	-0.28	2	2
NFKBIA	-0.007	0.029	-10000	0	-0.17	18	18
MAPK14	-0.005	0.01	0.24	1	-10000	0	1
NF kappa B1 p105/p50	-0.01	0.021	0.14	2	-0.18	7	9
ARRB2	-0.002	0.007	0.16	1	-10000	0	1
REL	-0.006	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	-0.011	0.024	0.14	2	-0.18	10	12
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	-0.01	0.022	0.14	2	-0.18	8	10
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
NF kappa B1 p50 dimer	-0.009	0.026	0.2	2	-0.21	7	9
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
NFKB1	-0.009	0.026	0.2	2	-0.21	7	9
RELA	-0.006	0.013	-10000	0	-0.31	1	1
positive regulation of anti-apoptosis	-0.006	0.022	-10000	0	-0.16	7	7
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	-0.014	0.032	-10000	0	-0.27	2	2
SRC	-0.006	0	-10000	0	-10000	0	0
PI3K	-0.015	0.12	0.17	98	-0.21	107	205
NF kappa B1 p50/RelA	-0.006	0.022	-10000	0	-0.16	7	7
IKBKB	-0.005	0.015	0.24	2	-10000	0	2
beta TrCP1/SCF ubiquitin ligase complex	-0.006	0	-10000	0	-10000	0	0
SYK	-0.008	0.034	0.24	2	-0.31	6	8
I kappa B alpha/PIK3R1	-0.01	0.038	-10000	0	-0.2	19	19
cell death	-0.014	0.031	-10000	0	-0.26	2	2
NF kappa B1 p105/c-Rel	-0.01	0.021	0.14	2	-0.18	7	9
LCK	-0.006	0	-10000	0	-10000	0	0
BCL3	-0.007	0.022	-10000	0	-0.31	3	3

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	-0.011	0.029	-10000	0	-0.21	12	12
MAP4K4	-0.033	0.074	-10000	0	-0.33	12	12
BAG4	-0.006	0	-10000	0	-10000	0	0
PKC zeta/ceramide	0.007	0.012	0.12	1	-10000	0	1
NFKBIA	-0.013	0.045	-10000	0	-0.31	13	13
BIRC3	-0.047	0.12	0.24	16	-0.31	90	106
BAX	0.004	0.007	-10000	0	-10000	0	0
RIPK1	-0.006	0	-10000	0	-10000	0	0
AKT1	-0.005	0.016	0.37	1	-10000	0	1
BAD	0.003	0.013	0.13	1	-10000	0	1
SMPD1	-0.014	0.033	-10000	0	-0.17	11	11
RB1	0.006	0.031	0.14	21	-0.14	4	25
FADD/Caspase 8	-0.034	0.076	-10000	0	-0.35	12	12
MAP2K4	-0.002	0.021	0.12	1	-0.14	9	10
NSMAF	-0.004	0.023	0.24	5	-10000	0	5
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0	0.013	0.12	1	-10000	0	1
EGF	-0.003	0.027	0.24	7	-10000	0	7
mol:ceramide	0.005	0.014	0.097	12	-10000	0	12
MADD	-0.006	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.011	0.029	-10000	0	-0.21	12	12
ASAH1	-0.006	0	-10000	0	-10000	0	0
negative regulation of cell cycle	0.006	0.031	0.14	21	-0.14	4	25
cell proliferation	-0.022	0.043	0.12	3	-0.2	13	16
BID	-0.018	0.058	-10000	0	-0.35	3	3
MAP3K1	0.002	0.017	0.13	1	-0.14	3	4
EIF2A	0.045	0.06	0.12	226	-10000	0	226
TRADD	-0.01	0.036	-10000	0	-0.31	8	8
CRADD	-0.006	0	-10000	0	-10000	0	0
MAPK3	-0.017	0.037	0.11	1	-0.16	12	13
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.014	0.03	0.11	1	-10000	0	1
Cathepsin D/ceramide	0.007	0.012	0.12	1	-10000	0	1
FADD	-0.034	0.074	-10000	0	-0.33	12	12
KSR1	0.003	0.013	0.13	1	-10000	0	1
MAPK8	0.002	0.018	-10000	0	-10000	0	0
PRKRA	0.003	0.016	0.13	4	-10000	0	4
PDGFA	-0.012	0.043	-10000	0	-0.31	12	12
TRAF2	-0.006	0	-10000	0	-10000	0	0
IGF1	-0.016	0.06	0.24	3	-0.31	21	24
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	0.005	0.014	0.097	12	-10000	0	12
CTSD	-0.008	0.025	-10000	0	-0.31	4	4
regulation of nitric oxide biosynthetic process	-0.01	0.024	-10000	0	-0.21	8	8
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.023	0.046	0.14	3	-0.21	13	16
PRKCD	-0.006	0.021	0.24	1	-0.31	2	3
PRKCZ	-0.006	0	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.011	0.029	-10000	0	-0.21	12	12
RelA/NF kappa B1	-0.01	0.024	-10000	0	-0.21	8	8
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	-0.006	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.034	0.079	-10000	0	-0.35	12	12
TNFR1A/BAG4/TNF-alpha	0.003	0.034	0.16	1	-0.18	19	20
mol:Sphingosine-1-phosphate	-0.011	0.029	-10000	0	-0.21	12	12
MAP2K1	-0.001	0.013	0.11	2	-10000	0	2
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	-0.006	0.013	-10000	0	-0.31	1	1
CYCS	0.023	0.048	0.13	93	-10000	0	93
TNFRSF1A	-0.016	0.054	-10000	0	-0.31	19	19
NFKB1	-0.01	0.033	-10000	0	-0.31	7	7
TNFR1A/BAG4	-0.014	0.037	-10000	0	-0.21	19	19
EIF2AK2	0.048	0.063	0.12	222	-10000	0	222
TNF-alpha/TNFR1A/FAN	0.004	0.037	0.16	6	-0.18	19	25
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	-0.022	0.07	-10000	0	-0.44	9	9
MAP2K2	-0.023	0.049	0.11	1	-0.13	88	89
SMPD3	-0.016	0.04	-10000	0	-0.21	11	11
TNF	-0.005	0.01	0.24	1	-10000	0	1
PKC zeta/PAR4	-0.007	0	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	-0.001	0.022	-10000	0	-0.15	6	6
NF kappa B1/RelA/I kappa B alpha	0.007	0.033	-10000	0	-0.17	19	19
AIFM1	0.027	0.054	0.14	94	-10000	0	94
BCL2	-0.055	0.11	0.24	1	-0.31	93	94

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.005	0.015	0.24	2	-10000	0	2
Syndecan-3/Src/Cortactin	0.006	0.084	-10000	0	-0.5	7	7
Syndecan-3/Neurocan	-0.015	0.057	-10000	0	-0.51	7	7
POMC	-0.005	0.01	0.24	1	-10000	0	1
EGFR	-0.03	0.083	0.24	1	-0.31	46	47
Syndecan-3/EGFR	-0.026	0.068	-10000	0	-0.53	7	7
AGRP	-0.006	0	-10000	0	-10000	0	0
NCSTN	-0.005	0.01	0.24	1	-10000	0	1
PSENEN	-0.016	0.054	-10000	0	-0.31	19	19
RP11-540L11.1	0	0	-10000	0	-10000	0	0
APH1B	-0.038	0.093	-10000	0	-0.31	61	61
APH1A	-0.005	0.01	0.24	1	-10000	0	1
NCAN	-0.006	0	-10000	0	-10000	0	0
long-term memory	-0.033	0.071	-10000	0	-0.5	7	7
Syndecan-3/IL8	0.001	0.076	-10000	0	-0.51	7	7
PSEN1	-0.005	0.01	0.24	1	-10000	0	1
Src/Cortactin	-0.006	0.01	0.17	2	-10000	0	2
FYN	-0.047	0.1	0.24	1	-0.31	79	80
limb bud formation	-0.014	0.059	-10000	0	-0.52	7	7
MC4R	0	0	-10000	0	-10000	0	0
SRC	-0.006	0	-10000	0	-10000	0	0
PTN	0.011	0.12	0.24	77	-0.31	32	109
FGFR/FGF/Syndecan-3	-0.014	0.059	-10000	0	-0.53	7	7
neuron projection morphogenesis	-0.01	0.076	-10000	0	-0.49	7	7
Syndecan-3/AgRP	-0.015	0.057	-10000	0	-0.51	7	7
Syndecan-3/AgRP/MC4R	-0.015	0.055	-10000	0	-0.49	7	7
Fyn/Cortactin	-0.034	0.072	0.17	3	-0.21	79	82
SDC3	-0.014	0.06	-10000	0	-0.53	7	7
GO:0007205	0	0	-10000	0	-10000	0	0
positive regulation of leukocyte migration	0.001	0.075	-10000	0	-0.5	7	7
IL8	0.019	0.074	0.24	57	-10000	0	57
Syndecan-3/Fyn/Cortactin	-0.034	0.073	-10000	0	-0.51	7	7
Syndecan-3/CASK	-0.013	0.057	-10000	0	-0.51	7	7
alpha-MSH/MC4R	-0.003	0.007	0.17	1	-10000	0	1
Gamma Secretase	-0.01	0.059	-10000	0	-0.15	79	79

×

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

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
BAG4	-0.006	0	-10000	0	-10000	0	0
Caspase 8 (4 units)	-0.013	0.036	-10000	0	-0.38	1	1
NEF	-0.002	0	-10000	0	-10000	0	0
NFKBIA	-0.023	0.06	-10000	0	-0.35	13	13
BIRC3	-0.059	0.16	0.45	16	-0.38	90	106
CYCS	-0.013	0.036	-10000	0	-0.37	1	1
RIPK1	-0.006	0	-10000	0	-10000	0	0
CD247	-0.008	0	-10000	0	-10000	0	0
MAP2K7	-0.01	0.043	-10000	0	-0.46	1	1
protein ubiquitination	-0.019	0.061	0.18	1	-0.35	2	3
CRADD	-0.006	0	-10000	0	-10000	0	0
DAXX	-0.005	0.015	0.24	2	-10000	0	2
FAS	-0.017	0.058	0.24	1	-0.31	21	22
BID	-0.012	0.036	-10000	0	-0.38	1	1
NF-kappa-B/RelA/I kappa B alpha	-0.049	0.088	-10000	0	-0.24	95	95
TRADD	-0.01	0.036	-10000	0	-0.31	8	8
MAP3K5	-0.006	0.023	0.24	2	-0.31	2	4
CFLAR	-0.006	0	-10000	0	-10000	0	0
FADD	-0.006	0	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.049	0.088	-10000	0	-0.24	95	95
MAPK8	-0.011	0.039	-10000	0	-0.44	1	1
APAF1	0.002	0.042	0.24	17	-10000	0	17
TRAF1	-0.006	0	-10000	0	-10000	0	0
TRAF2	-0.006	0	-10000	0	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.011	0.038	-10000	0	-0.19	22	22
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	-0.024	0.07	-10000	0	-0.32	7	7
CHUK	-0.021	0.065	-10000	0	-0.38	2	2
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.007	0.036	-10000	0	-0.16	22	22
TCRz/NEF	-0.007	0	-10000	0	-10000	0	0
TNF	-0.005	0.01	0.24	1	-10000	0	1
FASLG	-0.007	0	-10000	0	-10000	0	0
NFKB1	-0.02	0.052	-10000	0	-0.37	7	7
TNFR1A/BAG4/TNF-alpha	0.003	0.034	0.16	1	-0.18	19	20
CASP6	0.024	0.075	-10000	0	-0.33	1	1
CASP7	-0.07	0.17	0.33	15	-0.44	90	105
RELA	-0.016	0.037	-10000	0	-0.38	1	1
CASP2	0.001	0.041	0.24	16	-10000	0	16
CASP3	-0.069	0.17	0.33	15	-0.44	90	105
TNFRSF1A	-0.016	0.054	-10000	0	-0.31	19	19
TNFR1A/BAG4	-0.014	0.037	-10000	0	-0.21	19	19
CASP8	-0.006	0	-10000	0	-10000	0	0
CASP9	-0.005	0.01	0.24	1	-10000	0	1
MAP3K14	-0.024	0.066	-10000	0	-0.3	7	7
APAF-1/Caspase 9	-0.057	0.1	-10000	0	-0.28	89	89
BCL2	-0.032	0.058	-10000	0	-0.33	4	4

×

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

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
MAP4K1	-0.012	0.1	0.32	18	-10000	0	18
CRKL	-0.011	0.11	0.33	18	-10000	0	18
HRAS	-0.007	0.097	0.29	18	-10000	0	18
mol:PIP3	-0.006	0.11	0.32	17	-0.3	1	18
SPRED1	-0.008	0.03	0.24	1	-0.31	5	6
SPRED2	-0.006	0	-10000	0	-10000	0	0
GAB1	-0.009	0.11	0.35	18	-0.28	1	19
FOXO3	-0.009	0.1	0.31	18	-0.32	1	19
AKT1	-0.006	0.11	0.32	18	-10000	0	18
BAD	-0.007	0.1	0.31	18	-10000	0	18
megakaryocyte differentiation	-0.008	0.11	0.36	18	-0.27	2	20
GSK3B	-0.007	0.1	0.31	18	-10000	0	18
RAF1	-0.007	0.085	0.27	18	-10000	0	18
SHC1	-0.006	0	-10000	0	-10000	0	0
STAT3	-0.011	0.11	0.35	16	-0.28	2	18
STAT1	-0.014	0.22	0.54	10	-10000	0	10
HRAS/SPRED1	-0.006	0.086	0.26	18	-0.27	3	21
cell proliferation	-0.007	0.11	0.36	18	-0.27	2	20
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
TEC	0.013	0.066	0.24	44	-10000	0	44
RPS6KB1	-0.004	0.11	0.34	18	-10000	0	18
HRAS/SPRED2	-0.006	0.085	0.26	18	-10000	0	18
LYN/TEC/p62DOK	-0.007	0.1	0.49	2	-0.29	3	5
MAPK3	-0.019	0.072	0.23	12	-0.24	3	15
STAP1	-0.008	0.11	0.35	18	-0.28	1	19
GRAP2	-0.006	0	-10000	0	-10000	0	0
JAK2	-0.025	0.2	0.5	10	-10000	0	10
STAT1 (dimer)	-0.014	0.22	0.54	10	-0.54	7	17
mol:Gleevec	0.001	0.008	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.016	0.093	-10000	0	-0.29	3	3
actin filament polymerization	-0.006	0.11	0.35	18	-0.27	2	20
LYN	-0.014	0.048	-10000	0	-0.31	15	15
STAP1/STAT5A (dimer)	-0.019	0.15	0.39	17	-0.52	3	20
PIK3R1	-0.074	0.13	-10000	0	-0.31	131	131
CBL/CRKL/GRB2	-0.012	0.098	0.28	16	-10000	0	16
PI3K	-0.015	0.12	0.28	5	-0.34	15	20
PTEN	-0.012	0.042	-10000	0	-0.31	11	11
SCF/KIT/EPO/EPOR	-0.021	0.2	0.6	2	-10000	0	2
MAPK8	-0.007	0.12	0.36	18	-0.28	2	20
STAT3 (dimer)	-0.011	0.11	0.35	16	-0.28	2	18
positive regulation of transcription	-0.014	0.063	0.22	12	-0.19	3	15
mol:GDP	-0.008	0.1	0.29	18	-0.29	1	19
PIK3C2B	-0.008	0.12	0.36	18	-0.28	1	19
CBL/CRKL	-0.011	0.1	0.31	18	-10000	0	18
FER	-0.009	0.11	0.35	18	-0.28	2	20
SH2B3	-0.009	0.11	0.35	18	-0.28	2	20
PDPK1	-0.008	0.1	0.3	17	-0.29	1	18
SNAI2	-0.011	0.12	0.34	19	-0.34	6	25
positive regulation of cell proliferation	-0.017	0.18	0.44	16	-0.5	3	19
KITLG	0.002	0.029	0.25	4	-10000	0	4
cell motility	-0.017	0.18	0.44	16	-0.5	3	19
PTPN6	-0.003	0.014	-10000	0	-10000	0	0
EPOR	-0.021	0.14	0.78	1	-0.64	8	9
STAT5A (dimer)	-0.018	0.16	0.41	17	-0.53	3	20
SOCS1	-0.012	0.043	-10000	0	-0.31	12	12
cell migration	0.008	0.11	0.27	1	-0.34	18	19
SOS1	0.005	0.05	0.24	24	-10000	0	24
EPO	0	0.014	-10000	0	-10000	0	0
VAV1	-0.004	0.021	0.24	4	-10000	0	4
GRB10	-0.009	0.11	0.35	18	-0.28	1	19
PTPN11	-0.003	0.011	-10000	0	-10000	0	0
SCF/KIT	-0.006	0.12	0.38	18	-0.29	2	20
GO:0007205	0	0.01	-10000	0	-10000	0	0
MAP2K1	-0.006	0.073	0.24	18	-10000	0	18
CBL	-0.006	0	-10000	0	-10000	0	0
KIT	-0.011	0.16	0.54	18	-0.73	2	20
MAP2K2	-0.024	0.081	0.24	14	-0.24	16	30
SHC/Grb2/SOS1	-0.009	0.093	-10000	0	-0.26	2	2
STAT5A	-0.018	0.16	0.41	17	-0.55	3	20
GRB2	-0.006	0	-10000	0	-10000	0	0
response to radiation	-0.01	0.12	0.34	19	-0.33	6	25
SHC/GRAP2	-0.007	0	-10000	0	-10000	0	0
PTPRO	-0.008	0.12	0.36	18	-0.28	2	20
SH2B2	-0.007	0.11	0.35	18	-0.27	2	20
DOK1	-0.007	0.018	-10000	0	-0.31	2	2
MATK	-0.009	0.11	0.35	18	-0.28	1	19
CREBBP	-0.013	0.077	0.26	18	-0.32	11	29
BCL2	-0.16	0.43	0.79	1	-1.1	102	103

×

IL27-mediated signaling events

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
TGFB1	-0.054	0.11	-10000	0	-0.31	90	90
CD4-positive alpha-beta T cell lineage commitment	0	0.001	-10000	0	-10000	0	0
cytokine production during immune response	-0.002	0.085	0.51	5	-0.39	2	7
IL27/IL27R/JAK1	-0.01	0.095	0.48	1	-0.94	3	4
TBX21	0.043	0.1	0.44	5	-0.57	3	8
IL12B	-0.003	0.011	-10000	0	-10000	0	0
IL12A	0.007	0.045	0.2	28	-0.21	1	29
IL6ST	-0.012	0.053	-10000	0	-0.32	16	16
IL27RA/JAK1	-0.006	0.08	-10000	0	-1	3	3
IL27	-0.004	0.013	-10000	0	-10000	0	0
TYK2	-0.002	0.02	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.036	0.09	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.002	0.085	0.51	5	-0.39	2	7
T cell proliferation during immune response	-0.002	0.085	0.51	5	-0.39	2	7
MAPKKK cascade	0.002	0.085	0.39	2	-0.51	5	7
STAT3	-0.011	0.04	-10000	0	-0.31	10	10
STAT2	0.022	0.078	0.24	64	-10000	0	64
STAT1	0.13	0.12	0.24	314	-10000	0	314
IL12RB1	-0.004	0.006	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	0.046	0.11	0.52	7	-0.57	3	10
IL27/IL27R/JAK2/TYK2	0.002	0.086	0.39	2	-0.51	5	7
positive regulation of T cell mediated cytotoxicity	0.002	0.085	0.39	2	-0.51	5	7
STAT1 (dimer)	0.06	0.12	0.47	5	-0.79	3	8
JAK2	-0.003	0.029	0.27	2	-0.31	2	4
JAK1	-0.007	0.018	-10000	0	-0.31	2	2
STAT2 (dimer)	0.017	0.095	0.38	10	-0.44	5	15
T cell proliferation	-0.001	0.085	0.42	2	-0.49	5	7
IL12/IL12R/TYK2/JAK2	0.026	0.075	0.42	3	-10000	0	3
IL17A	-0.036	0.09	-10000	0	-10000	0	0
mast cell activation	-0.002	0.085	0.51	5	-0.39	2	7
IFNG	0.009	0.044	0.2	26	-10000	0	26
T cell differentiation	0	0.005	0.021	24	-0.023	3	27
STAT3 (dimer)	-0.003	0.082	0.34	2	-0.52	5	7
STAT5A (dimer)	-0.003	0.08	0.34	2	-0.49	5	7
STAT4 (dimer)	0	0.078	0.34	2	-0.47	5	7
STAT4	-0.004	0.018	0.24	3	-10000	0	3
T cell activation	0	0.012	0.12	3	-0.18	1	4
IL27R/JAK2/TYK2	-0.005	0.099	0.39	2	-0.97	3	5
GATA3	-0.003	0.033	-10000	0	-10000	0	0
IL18	0.036	0.08	0.2	108	-10000	0	108
positive regulation of mast cell cytokine production	-0.003	0.081	0.33	2	-0.45	7	9
IL27/EBI3	-0.003	0.023	0.15	1	-10000	0	1
IL27RA	-0.003	0.085	0.37	1	-1.1	3	4
IL6	-0.007	0.05	0.24	10	-0.31	9	19
STAT5A	-0.01	0.036	-10000	0	-0.31	8	8
monocyte differentiation	0.001	0.002	0.015	1	-10000	0	1
IL2	-0.001	0.041	0.45	3	-0.41	1	4
IL1B	0.011	0.052	0.2	40	-10000	0	40
EBI3	-0.004	0.013	-10000	0	-10000	0	0
TNF	-0.003	0.009	0.2	1	-10000	0	1

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	-0.016	0.061	-10000	0	-0.39	13	13
KLHL20	-0.046	0.068	0.3	1	-0.29	7	8
CYFIP2	-0.012	0.042	-10000	0	-0.31	11	11
Rac1/GDP	-0.022	0.042	-10000	0	-0.24	14	14
ENAH	-0.017	0.06	-10000	0	-0.39	13	13
AP1M1	-0.004	0.018	0.24	3	-10000	0	3
RAP1B	-0.004	0.023	0.24	5	-10000	0	5
RAP1A	-0.005	0.01	0.24	1	-10000	0	1
CTNNB1	-0.005	0.015	0.24	2	-10000	0	2
CDC42/GTP	-0.023	0.029	-10000	0	-0.21	5	5
ABI1/Sra1/Nap1	-0.037	0.045	-10000	0	-0.13	31	31
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.002	0.029	0.15	3	-0.16	14	17
RAPGEF1	-0.019	0.053	-10000	0	-0.35	13	13
CTNND1	-0.006	0.001	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.015	0.062	-10000	0	-0.4	13	13
CRK	-0.018	0.057	-10000	0	-0.37	13	13
E-cadherin/gamma catenin/alpha catenin	-0.005	0.042	-10000	0	-0.19	26	26
alphaE/beta7 Integrin	-0.007	0.011	0.17	1	-0.21	1	2
IQGAP1	-0.006	0.021	0.24	1	-0.31	2	3
NCKAP1	-0.002	0.031	0.24	9	-10000	0	9
Rap1/GTP/I-afadin	-0.003	0.04	0.15	6	-0.16	29	35
DLG1	-0.003	0.073	-10000	0	-0.39	13	13
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.031	0.039	-10000	0	-0.16	16	16
MLLT4	-0.021	0.066	-10000	0	-0.31	29	29
ARF6/GTP/NME1/Tiam1	0.011	0.035	0.15	31	-0.16	2	33
PI3K	-0.039	0.049	-10000	0	-0.2	16	16
ARF6	-0.006	0.013	-10000	0	-0.31	1	1
mol:Ca2+	0	0	-10000	0	-10000	0	0
E-cadherin/gamma catenin	-0.016	0.045	-10000	0	-0.23	24	24
TIAM1	-0.006	0.019	0.24	2	-0.31	1	3
E-cadherin(dimer)/Ca2+	0.001	0.028	-10000	0	-0.15	15	15
AKT1	-0.025	0.03	-10000	0	-0.14	8	8
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
CDH1	-0.013	0.045	-10000	0	-0.31	13	13
RhoA/GDP	-0.02	0.041	-10000	0	-0.24	14	14
actin cytoskeleton organization	-0.034	0.051	0.25	1	-0.22	6	7
CDC42/GDP	-0.02	0.041	-10000	0	-0.24	14	14
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.012	0.042	-10000	0	-0.2	26	26
ITGB7	-0.006	0.016	0.24	1	-0.31	1	2
RAC1	-0.006	0.013	-10000	0	-0.31	1	1
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.001	0.03	-10000	0	-0.16	15	15
E-cadherin/Ca2+/beta catenin/alpha catenin	0	0.026	0.14	2	-0.15	15	17
mol:GDP	-0.021	0.047	-10000	0	-0.28	14	14
CDC42/GTP/IQGAP1	0.003	0.013	0.15	1	-0.18	2	3
JUP	-0.013	0.045	-10000	0	-0.31	13	13
p120 catenin/RhoA/GDP	-0.021	0.042	-10000	0	-0.24	14	14
RAC1/GTP/IQGAP1	0.002	0.015	0.15	1	-0.18	3	4
PIP5K1C/AP1M1	-0.006	0.013	0.17	3	-10000	0	3
RHOA	-0.007	0.018	-10000	0	-0.31	2	2
CDC42	-0.006	0	-10000	0	-10000	0	0
CTNNA1	-0.007	0.018	-10000	0	-0.31	2	2
positive regulation of S phase of mitotic cell cycle	-0.045	0.07	0.36	1	-0.16	149	150
NME1	0.007	0.054	0.24	29	-10000	0	29
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	-0.016	0.061	-10000	0	-0.39	13	13
regulation of cell-cell adhesion	-0.021	0.026	-10000	0	-0.19	5	5
WASF2	-0.031	0.035	-10000	0	-0.12	31	31
Rap1/GTP	-0.022	0.035	-10000	0	-0.25	4	4
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.004	0.039	-10000	0	-0.16	27	27
CCND1	-0.056	0.086	0.39	1	-0.19	149	150
VAV2	-0.022	0.078	-10000	0	-0.46	14	14
RAP1/GDP	-0.02	0.039	-10000	0	-0.24	6	6
adherens junction assembly	-0.016	0.059	-10000	0	-0.38	13	13
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	-0.005	0.01	0.24	1	-10000	0	1
PIP5K1C	-0.006	0	-10000	0	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.019	0.034	-10000	0	-0.28	2	2
E-cadherin/beta catenin	-0.008	0.039	-10000	0	-0.27	12	12
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	-0.017	0.06	-10000	0	-0.39	13	13
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
Rac1/GTP	-0.07	0.1	0.4	1	-0.41	12	13
E-cadherin/beta catenin/alpha catenin	0	0.031	0.16	2	-0.18	15	17
ITGAE	-0.006	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.015	0.063	-10000	0	-0.41	13	13

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	0.006	0.018	0.15	4	-0.17	3	7
EFNA5	-0.006	0.03	0.24	4	-0.31	3	7
FYN	-0.028	0.055	0.14	4	-0.16	80	84
neuron projection morphogenesis	0.006	0.018	0.15	4	-0.17	3	7
cell-cell signaling	0	0	-10000	0	-10000	0	0
Ephrin A5/EPHA5	0.006	0.018	0.15	4	-0.18	3	7
EPHA5	-0.006	0	-10000	0	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	-0.026	0.088	0.19	28	-0.22	78	106
AKT1	-0.049	0.11	-10000	0	-0.36	3	3
PTK2B	-0.049	0.1	0.26	8	-0.28	40	48
VEGFR2 homodimer/Frs2	-0.045	0.078	0.27	2	-0.25	2	4
CAV1	-0.053	0.11	0.24	2	-0.31	90	92
CALM1	-0.012	0.042	-10000	0	-0.31	11	11
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.032	0.087	0.35	2	-0.28	2	4
endothelial cell proliferation	-0.041	0.089	-10000	0	-0.33	3	3
mol:Ca2+	-0.037	0.077	0.36	1	-0.34	2	3
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.035	0.083	0.3	2	-0.28	4	6
RP11-342D11.1	-0.037	0.077	0.36	1	-0.34	2	3
CDH5	-0.006	0	-10000	0	-10000	0	0
VEGFA homodimer	0.023	0.043	0.15	53	-0.16	3	56
SHC1	-0.006	0	-10000	0	-10000	0	0
SHC2	-0.023	0.071	-10000	0	-0.31	33	33
HRAS/GDP	-0.046	0.054	-10000	0	-0.31	2	2
SH2D2A	-0.006	0	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.034	0.08	0.26	1	-10000	0	1
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.036	0.085	0.39	1	-0.28	2	3
VEGFR1 homodimer	-0.006	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.034	0.077	0.24	2	-0.33	2	4
GRB10	-0.038	0.077	0.36	1	-0.34	2	3
PTPN11	-0.006	0	-10000	0	-10000	0	0
GRB2	-0.006	0	-10000	0	-10000	0	0
PAK1	0.002	0.043	0.24	18	-10000	0	18
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.035	0.079	0.29	2	-0.26	3	5
HRAS	-0.006	0	-10000	0	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	-0.041	0.1	0.28	2	-0.3	38	40
HIF1A	-0.007	0.022	-10000	0	-0.31	3	3
FRS2	0.001	0.04	0.24	15	-10000	0	15
oxygen and reactive oxygen species metabolic process	-0.036	0.079	-10000	0	-0.28	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	-0.006	0	-10000	0	-10000	0	0
Nck/Pak	0.012	0.054	0.17	60	-10000	0	60
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.056	0.098	0.39	1	-0.31	19	20
mol:GDP	-0.037	0.07	-10000	0	-0.32	2	2
mol:NADP	-0.032	0.069	0.25	1	-10000	0	1
eNOS/Hsp90	-0.032	0.067	-10000	0	-10000	0	0
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
mol:IP3	-0.038	0.077	0.36	1	-0.35	2	3
HIF1A/ARNT	-0.008	0.017	0.17	1	-0.21	3	4
SHB	-0.006	0	-10000	0	-10000	0	0
VEGFA	0.013	0.07	0.24	49	-10000	0	49
VEGFC	-0.047	0.1	-10000	0	-0.31	77	77
FAK1/Vinculin	-0.05	0.12	0.31	3	-0.33	37	40
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	-0.007	0.018	-10000	0	-0.31	2	2
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.046	0.11	0.31	8	-0.3	39	47
PTPN6	-0.006	0	-10000	0	-10000	0	0
EPAS1	-0.08	0.13	0.18	2	-0.31	132	134
mol:L-citrulline	-0.032	0.069	0.25	1	-10000	0	1
ITGAV	0.001	0.05	0.24	19	-0.31	3	22
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.031	0.083	0.3	3	-0.26	2	5
VEGFR2 homodimer/VEGFA homodimer	-0.038	0.088	0.32	2	-0.37	2	4
VEGFR2/3 heterodimer	-0.05	0.075	0.27	2	-0.25	2	4
VEGFB	-0.017	0.057	-10000	0	-0.31	21	21
MAPK11	-0.038	0.081	0.39	1	-0.36	2	3
VEGFR2 homodimer	-0.057	0.092	0.4	2	-0.29	2	4
FLT1	-0.006	0	-10000	0	-10000	0	0
NEDD4	-0.007	0.016	0.24	2	-10000	0	2
MAPK3	-0.037	0.074	0.35	1	-0.32	2	3
MAPK1	-0.036	0.072	0.35	1	-0.32	2	3
VEGFA145/NRP2	0.016	0.064	0.18	74	-10000	0	74
VEGFR1/2 heterodimer	-0.05	0.075	0.27	2	-0.25	2	4
KDR	-0.057	0.092	0.41	2	-0.29	2	4
VEGFA165/NRP1/VEGFR2 homodimer	-0.028	0.089	0.31	4	-0.34	2	6
SRC	-0.006	0	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	-0.037	0.074	0.36	1	-0.33	2	3
PI3K	-0.041	0.11	-10000	0	-0.36	3	3
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.024	0.098	0.32	5	-0.28	2	7
FES	-0.039	0.078	0.36	1	-0.35	2	3
GAB1	-0.04	0.087	0.28	2	-0.37	4	6
VEGFR2 homodimer/VEGFA homodimer/Src	-0.036	0.085	0.39	1	-0.28	2	3
CTNNB1	-0.005	0.015	0.24	2	-10000	0	2
SOS1	0.005	0.05	0.24	24	-10000	0	24
ARNT	-0.005	0.01	0.24	1	-10000	0	1
eNOS/Caveolin-1	-0.048	0.084	-10000	0	-0.35	4	4
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.029	0.087	0.39	1	-0.28	2	3
PI3K/GAB1	-0.069	0.14	-10000	0	-0.37	32	32
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.016	0.095	0.28	13	-0.26	2	15
PRKACA	-0.006	0	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.068	0.083	-10000	0	-0.31	19	19
HSP90AA1	-0.006	0.013	-10000	0	-0.31	1	1
CDC42	-0.039	0.078	0.36	1	-0.35	2	3
actin cytoskeleton reorganization	-0.036	0.084	0.39	1	-0.28	2	3
PTK2	-0.052	0.12	0.33	3	-0.34	39	42
EDG1	-0.04	0.084	0.36	1	-0.43	6	7
mol:DAG	-0.038	0.077	0.36	1	-0.35	2	3
CaM/Ca2+	-0.04	0.071	-10000	0	-0.29	5	5
MAP2K3	-0.038	0.076	0.29	2	-0.34	2	4
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.037	0.084	0.31	2	-0.35	2	4
PLCG1	-0.038	0.078	0.36	1	-0.35	2	3
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.034	0.081	0.3	2	-0.26	2	4
IQGAP1	-0.006	0.021	0.24	1	-0.31	2	3
YES1	0.006	0.052	0.24	26	-10000	0	26
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.036	0.085	0.39	1	-0.28	2	3
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.036	0.085	0.39	1	-0.28	2	3
cell migration	-0.05	0.11	0.3	3	-0.4	9	12
mol:PI-3-4-5-P3	-0.038	0.1	-10000	0	-0.35	2	2
FYN	-0.047	0.1	0.24	1	-0.31	79	80
VEGFB/NRP1	-0.041	0.079	0.33	1	-0.29	12	13
mol:NO	-0.032	0.069	0.25	1	-10000	0	1
PXN	-0.01	0.033	-10000	0	-0.31	7	7
HRAS/GTP	-0.045	0.054	-10000	0	-0.31	2	2
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.037	0.084	0.39	1	-0.35	2	3
VHL	-0.004	0.018	0.24	3	-10000	0	3
ITGB3	-0.041	0.11	0.24	12	-0.31	77	89
NOS3	-0.035	0.074	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.044	0.092	0.39	1	-0.3	10	11
RAC1	-0.006	0.013	-10000	0	-0.31	1	1
PRKCA	-0.037	0.076	0.29	2	-0.31	4	6
PRKCB	-0.036	0.072	0.34	1	-0.33	2	3
VCL	-0.005	0.015	0.24	2	-10000	0	2
VEGFA165/NRP1	-0.034	0.082	0.38	1	-0.34	2	3
VEGFR1/2 heterodimer/VEGFA homodimer	-0.036	0.085	0.39	1	-0.28	2	3
VEGFA165/NRP2	0.016	0.064	0.18	74	-10000	0	74
MAPKKK cascade	-0.033	0.076	0.34	1	-0.31	2	3
NRP2	0.006	0.054	0.24	28	-10000	0	28
VEGFC homodimer	-0.047	0.1	-10000	0	-0.31	77	77
NCK1	0.012	0.065	0.24	42	-10000	0	42
ROCK1	-0.005	0.01	0.24	1	-10000	0	1
FAK1/Paxillin	-0.052	0.12	0.31	3	-0.33	40	43
MAP3K13	-0.037	0.081	0.32	2	-0.35	2	4
PDPK1	-0.039	0.094	-10000	0	-0.32	2	2

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	-0.005	0.025	0.2	6	-10000	0	6
NFATC2	-0.045	0.17	0.38	5	-0.54	16	21
NFATC3	0.005	0.046	0.27	4	-0.27	1	5
CD40LG	-0.015	0.17	0.63	6	-0.94	1	7
ITCH	-0.007	0.057	0.42	5	-10000	0	5
CBLB	-0.008	0.055	0.28	15	-10000	0	15
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.037	0.14	0.59	9	-0.56	4	13
JUNB	-0.077	0.13	-10000	0	-0.31	135	135
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.016	0.029	-10000	0	-0.22	11	11
T cell anergy	-0.01	0.07	0.36	13	-10000	0	13
TLE4	-0.059	0.18	0.4	1	-0.56	55	56
Jun/NFAT1-c-4/p21SNFT	-0.006	0.14	-10000	0	-0.94	1	1
AP-1/NFAT1-c-4	-0.01	0.19	0.58	5	-1.1	1	6
IKZF1	-0.028	0.11	-10000	0	-0.38	15	15
T-helper 2 cell differentiation	-0.021	0.13	-10000	0	-0.56	6	6
AP-1/NFAT1	-0.028	0.14	0.33	13	-0.37	30	43
CALM1	-0.014	0.049	-10000	0	-0.32	11	11
EGR2	-0.007	0.13	0.75	3	-0.86	1	4
EGR3	-0.008	0.12	0.7	2	-0.86	1	3
NFAT1/FOXP3	-0.028	0.12	0.4	7	-0.39	15	22
EGR1	-0.12	0.15	0.24	3	-0.31	212	215
JUN	0.005	0.047	0.22	18	-0.31	1	19
EGR4	-0.006	0.004	-10000	0	-10000	0	0
mol:Ca2+	-0.002	0.022	0.13	15	-10000	0	15
GBP3	-0.039	0.19	0.42	24	-0.56	43	67
FOSL1	-0.006	0	-10000	0	-10000	0	0
NFAT1-c-4/MAF/IRF4	-0.016	0.12	-10000	0	-0.94	1	1
DGKA	-0.024	0.12	0.43	7	-0.38	15	22
CREM	-0.005	0.01	0.24	1	-10000	0	1
NFAT1-c-4/PPARG	-0.015	0.12	-10000	0	-0.98	1	1
CTLA4	-0.024	0.11	0.51	7	-0.33	14	21
NFAT1-c-4 (dimer)/EGR1	-0.075	0.14	0.47	1	-1.1	1	2
NFAT1-c-4 (dimer)/EGR4	-0.017	0.12	0.47	1	-0.98	1	2
FOS	-0.019	0.11	0.25	26	-0.31	53	79
IFNG	-0.021	0.15	0.47	25	-0.52	4	29
T cell activation	-0.013	0.12	0.59	2	-0.58	1	3
MAF	-0.006	0	-10000	0	-10000	0	0
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.003	0.11	1.2	1	-0.63	3	4
TNF	-0.072	0.14	0.6	2	-0.97	1	3
FASLG	-0.008	0.13	0.74	1	-0.93	1	2
TBX21	0.003	0.044	0.2	26	-10000	0	26
BATF3	0	0	-10000	0	-10000	0	0
PRKCQ	-0.01	0.048	0.24	5	-0.31	11	16
PTPN1	-0.028	0.11	-10000	0	-0.39	14	14
NFAT1-c-4/ICER1	-0.016	0.12	-10000	0	-0.98	1	1
GATA3	-0.005	0.015	0.24	2	-10000	0	2
T-helper 1 cell differentiation	-0.02	0.15	0.47	25	-0.51	4	29
IL2RA	-0.039	0.14	0.56	8	-0.55	5	13
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.024	0.12	0.43	9	-0.38	15	24
E2F1	-0.005	0.013	0.15	1	-10000	0	1
PPARG	-0.004	0.023	0.24	5	-10000	0	5
SLC3A2	-0.027	0.12	0.41	2	-0.39	14	16
IRF4	-0.005	0.015	0.24	2	-10000	0	2
PTGS2	-0.011	0.18	0.68	9	-0.94	1	10
CSF2	-0.015	0.17	0.63	6	-0.94	1	7
JunB/Fra1/NFAT1-c-4	-0.051	0.14	-10000	0	-0.8	2	2
IL4	-0.022	0.14	-10000	0	-0.57	6	6
IL5	-0.015	0.17	0.63	6	-0.94	1	7
IL2	-0.013	0.12	0.59	2	-0.58	1	3
IL3	-0.018	0.023	-10000	0	-10000	0	0
RNF128	-0.007	0.059	0.3	15	-10000	0	15
NFATC1	-0.003	0.11	0.63	3	-1.2	1	4
CDK4	0.008	0.11	0.62	4	-0.64	1	5
PTPRK	-0.03	0.13	0.4	3	-0.44	20	23
IL8	0.003	0.21	0.67	13	-0.94	1	14
POU2F1	-0.006	0	-10000	0	-10000	0	0

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	0.097	0.22	0.58	9	-10000	0	9
PCK1	0.15	0.21	0.55	59	-10000	0	59
HNF4A	0.13	0.26	0.67	18	-10000	0	18
KCNJ11	0.1	0.24	0.61	6	-10000	0	6
AKT1	0.072	0.15	0.37	25	-10000	0	25
response to starvation	0.015	0.029	0.15	1	-10000	0	1
DLK1	0.12	0.26	0.74	17	-10000	0	17
NKX2-1	0.073	0.15	-10000	0	-10000	0	0
ACADM	0.1	0.23	0.57	13	-10000	0	13
TAT	0.1	0.17	0.51	11	-10000	0	11
CEBPB	-0.007	0.028	0.19	2	-0.31	4	6
CEBPA	-0.006	0.008	-10000	0	-10000	0	0
TTR	0.092	0.14	0.99	2	-10000	0	2
PKLR	0.096	0.22	0.56	8	-10000	0	8
APOA1	0.16	0.31	0.77	44	-10000	0	44
CPT1C	0.1	0.23	0.62	14	-10000	0	14
ALAS1	0.067	0.16	0.78	2	-10000	0	2
TFRC	0.21	0.3	0.75	78	-10000	0	78
FOXF1	-0.006	0	-10000	0	-10000	0	0
NF1	-0.019	0.065	0.18	4	-0.31	26	30
HNF1A (dimer)	-0.007	0.009	-10000	0	-0.22	1	1
CPT1A	0.095	0.22	0.57	7	-0.94	1	8
HMGCS1	0.12	0.25	0.6	42	-10000	0	42
NR3C1	-0.012	0.04	-10000	0	-0.31	10	10
CPT1B	0.096	0.22	0.57	7	-10000	0	7
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	-0.007	0.009	-10000	0	-0.22	1	1
GCK	0.096	0.22	0.57	7	-10000	0	7
CREB1	0.027	0.07	0.18	102	-10000	0	102
IGFBP1	0.073	0.15	0.49	2	-10000	0	2
PDX1	0.07	0.16	-10000	0	-1	1	1
UCP2	-0.007	0.37	0.56	8	-0.76	63	71
ALDOB	0.1	0.24	0.61	5	-10000	0	5
AFP	0.037	0.053	0.56	1	-10000	0	1
BDH1	0.095	0.23	0.58	9	-0.77	1	10
HADH	0.083	0.27	0.61	6	-0.88	6	12
F2	0.13	0.27	0.72	12	-10000	0	12
HNF1A	-0.007	0.009	-10000	0	-0.22	1	1
G6PC	0.038	0.062	-10000	0	-10000	0	0
SLC2A2	0.082	0.18	0.52	2	-10000	0	2
INS	-0.005	0.015	-10000	0	-0.18	4	4
FOXA1	-0.006	0.025	0.31	3	-10000	0	3
FOXA3	0.091	0.12	0.35	38	-10000	0	38
FOXA2	0.15	0.32	0.83	23	-10000	0	23
ABCC8	0.1	0.24	0.61	6	-10000	0	6
ALB	0.037	0.055	0.49	2	-10000	0	2

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	0.006	0	-10000	0	-10000	0	0
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	-0.006	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.03	0.087	0.24	82	-10000	0	82
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	-0.009	0.031	-10000	0	-0.31	6	6
RAC1-CDC42/GTP/PAK family	-0.045	0.076	-10000	0	-0.17	158	158
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.006	0.052	0.24	26	-10000	0	26
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	-0.006	0	-10000	0	-10000	0	0
FYN	-0.047	0.1	0.24	1	-0.31	79	80
MAP3K12	-0.006	0	-10000	0	-10000	0	0
FGR	-0.006	0	-10000	0	-10000	0	0
p38 alpha/TAB1	-0.019	0.056	-10000	0	-0.24	4	4
PRKG1	-0.005	0.01	0.24	1	-10000	0	1
DUSP8	-0.006	0	-10000	0	-10000	0	0
PGK/cGMP/p38 alpha	-0.025	0.047	0.13	1	-0.24	4	5
apoptosis	-0.02	0.053	-10000	0	-0.24	4	4
RAL/GTP	0.006	0.009	0.15	2	-10000	0	2
LYN	-0.014	0.048	-10000	0	-0.31	15	15
DUSP1	-0.065	0.12	0.24	3	-0.31	114	117
PAK1	0.002	0.043	0.24	18	-10000	0	18
SRC	-0.006	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.01	0.012	-10000	0	-0.16	3	3
TRAF6	-0.005	0.015	0.24	2	-10000	0	2
RAC1	-0.006	0.013	-10000	0	-0.31	1	1
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	-0.006	0	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0.006	0.008	-10000	0	-0.18	1	1
MAPK11	-0.024	0.078	0.17	6	-0.24	22	28
BLK	-0.005	0.01	0.24	1	-10000	0	1
HCK	-0.005	0.01	0.24	1	-10000	0	1
MAP2K3	-0.007	0.018	-10000	0	-0.31	2	2
DUSP16	-0.004	0.023	0.24	5	-10000	0	5
DUSP10	0.003	0.047	0.24	21	-10000	0	21
TRAF6/MEKK3	0.006	0.008	0.15	2	-10000	0	2
MAP3K7IP1	-0.006	0	-10000	0	-10000	0	0
MAPK14	-0.018	0.06	-10000	0	-0.26	4	4
positive regulation of innate immune response	-0.028	0.084	0.18	5	-0.26	22	27
LCK	-0.006	0	-10000	0	-10000	0	0
p38alpha-beta/MKP7	-0.027	0.084	0.21	4	-0.25	22	26
p38alpha-beta/MKP5	-0.024	0.084	0.22	2	-0.32	3	5
PGK/cGMP	-0.003	0.007	0.17	1	-10000	0	1
PAK2	-0.004	0.018	0.24	3	-10000	0	3
p38alpha-beta/MKP1	-0.042	0.098	-10000	0	-0.29	36	36
CDC42	-0.006	0	-10000	0	-10000	0	0
RALB	-0.006	0	-10000	0	-10000	0	0
RALA	-0.005	0.015	0.24	2	-10000	0	2
PAK3	-0.094	0.14	0.24	2	-0.31	167	169

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.004	0.081	0.5	13	-10000	0	13
regulation of axonogenesis	-0.011	0.043	0.32	1	-0.16	16	17
myoblast fusion	-0.005	0.045	-10000	0	-0.28	13	13
mol:GTP	0.008	0.029	0.18	13	-0.29	1	14
regulation of calcium-dependent cell-cell adhesion	-0.019	0.048	0.18	2	-0.23	13	15
ARF1/GTP	0	0.048	0.15	11	-0.19	28	39
mol:GM1	0.003	0.026	0.16	13	-0.22	1	14
mol:Choline	0.007	0.044	0.15	47	-0.2	1	48
lamellipodium assembly	0.003	0.049	0.29	13	-0.4	1	14
MAPK3	-0.001	0.057	0.32	13	-0.19	14	27
ARF6/GTP/NME1/Tiam1	0.019	0.048	0.24	13	-0.18	2	15
ARF1	-0.021	0.066	-10000	0	-0.31	29	29
ARF6/GDP	0.005	0.045	0.28	13	-10000	0	13
ARF1/GDP	0.002	0.043	0.24	11	-0.21	6	17
ARF6	0.008	0.016	-10000	0	-10000	0	0
RAB11A	-0.006	0	-10000	0	-10000	0	0
TIAM1	-0.005	0.02	0.24	2	-0.31	1	3
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.004	0.05	0.31	14	-0.2	2	16
actin filament bundle formation	0.001	0.02	0.28	1	-10000	0	1
KALRN	-0.004	0.02	-10000	0	-0.28	1	1
RAB11FIP3/RAB11A	-0.007	0	-10000	0	-10000	0	0
RhoA/GDP	-0.001	0.02	-10000	0	-0.28	1	1
NME1	0.007	0.055	0.24	29	-10000	0	29
Rac1/GDP	-0.001	0.019	-10000	0	-0.28	1	1
substrate adhesion-dependent cell spreading	0.008	0.029	0.18	13	-0.29	1	14
cortical actin cytoskeleton organization	0.003	0.049	0.29	13	-0.4	1	14
RAC1	-0.006	0.013	-10000	0	-0.31	1	1
liver development	0.008	0.029	0.18	13	-0.29	1	14
ARF6/GTP	0.008	0.029	0.18	13	-0.29	1	14
RhoA/GTP	0.009	0.027	0.15	13	-0.2	3	16
mol:GDP	0.007	0.051	0.33	13	-0.3	1	14
ARF6/GTP/RAB11FIP3/RAB11A	0.012	0.022	0.14	13	-0.2	1	14
RHOA	-0.007	0.018	-10000	0	-0.31	2	2
PLD1	0.011	0.051	0.18	47	-0.23	1	48
RAB11FIP3	-0.006	0	-10000	0	-10000	0	0
tube morphogenesis	0.003	0.049	0.29	13	-0.4	1	14
ruffle organization	0.011	0.043	0.16	16	-0.32	1	17
regulation of epithelial cell migration	0.008	0.029	0.18	13	-0.29	1	14
PLD2	0	0.027	0.16	13	-0.23	1	14
PIP5K1A	0.011	0.043	0.16	16	-0.32	1	17
mol:Phosphatidic acid	0.007	0.044	0.15	47	-0.2	1	48
Rac1/GTP	0.003	0.049	0.29	13	-0.41	1	14

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	-0.048	0.11	-10000	0	-0.46	17	17
BAG4	-0.006	0	-10000	0	-10000	0	0
BAD	-0.019	0.034	-10000	0	-0.15	12	12
NFKBIA	-0.013	0.045	-10000	0	-0.31	13	13
BIRC3	-0.047	0.12	0.24	16	-0.31	90	106
BAX	-0.019	0.034	-10000	0	-0.15	12	12
EnzymeConsortium:3.1.4.12	-0.012	0.026	-10000	0	-0.095	18	18
IKBKB	-0.048	0.11	-10000	0	-0.51	12	12
MAP2K2	-0.039	0.054	-10000	0	-0.22	16	16
MAP2K1	-0.022	0.03	-10000	0	-0.16	6	6
SMPD1	-0.013	0.026	-10000	0	-0.11	12	12
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	-0.048	0.11	-10000	0	-0.54	12	12
MAP2K4	-0.022	0.035	-10000	0	-0.14	19	19
protein ubiquitination	-0.047	0.11	-10000	0	-0.52	12	12
EnzymeConsortium:2.7.1.37	-0.031	0.039	-10000	0	-0.2	9	9
response to UV	0	0	-10000	0	-0.002	9	9
RAF1	-0.021	0.032	-10000	0	-0.15	12	12
CRADD	-0.006	0	-10000	0	-10000	0	0
mol:ceramide	-0.018	0.036	-10000	0	-0.16	12	12
I-kappa-B-alpha/RELA/p50/ubiquitin	0.001	0.028	-10000	0	-0.18	14	14
MADD	-0.006	0	-10000	0	-10000	0	0
MAP3K1	-0.02	0.036	-10000	0	-0.15	16	16
TRADD	-0.01	0.036	-10000	0	-0.31	8	8
RELA/p50	-0.006	0.013	-10000	0	-0.31	1	1
MAPK3	-0.034	0.045	-10000	0	-0.18	21	21
MAPK1	-0.031	0.042	-10000	0	-0.18	15	15
p50/RELA/I-kappa-B-alpha	-0.012	0.032	-10000	0	-0.21	14	14
FADD	-0.049	0.11	-10000	0	-0.44	18	18
KSR1	-0.02	0.034	-10000	0	-0.16	12	12
MAPK8	-0.021	0.033	0.1	1	-0.14	10	11
TRAF2	-0.004	0.004	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-0.002	1	1
CHUK	-0.044	0.11	-10000	0	-0.5	12	12
TNF R/SODD	-0.012	0.037	-10000	0	-0.21	19	19
TNF	-0.006	0.01	0.24	1	-10000	0	1
CYCS	-0.005	0.047	0.12	4	-0.15	9	13
IKBKG	-0.048	0.11	-10000	0	-0.51	12	12
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.049	0.12	-10000	0	-0.44	20	20
RELA	-0.006	0.013	-10000	0	-0.31	1	1
RIPK1	-0.004	0.004	-10000	0	-10000	0	0
AIFM1	-0.003	0.05	0.12	16	-0.15	9	25
TNF/TNF R/SODD	0	0.034	0.16	1	-0.18	19	20
TNFRSF1A	-0.014	0.055	-10000	0	-0.31	19	19
response to heat	0	0	-10000	0	-0.002	1	1
CASP8	-0.009	0.047	-10000	0	-0.9	1	1
NSMAF	-0.048	0.11	-10000	0	-0.42	19	19
response to hydrogen peroxide	0	0	-10000	0	-0.002	9	9
BCL2	-0.055	0.11	0.24	1	-0.31	93	94

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	0.004	0.093	0.46	11	-0.88	3	14
MKNK1	-0.006	0	-10000	0	-10000	0	0
MAPK14	-0.003	0.039	0.19	11	-0.28	3	14
ATF2/c-Jun	0.005	0.075	0.43	14	-0.38	2	16
MAPK11	-0.003	0.038	0.18	10	-0.28	3	13
MITF	0.001	0.043	0.21	10	-0.33	3	13
MAPKAPK5	0.001	0.043	0.21	10	-0.33	3	13
KRT8	0.002	0.046	0.21	10	-0.31	4	14
MAPKAPK3	-0.006	0	-10000	0	-10000	0	0
MAPKAPK2	-0.006	0	-10000	0	-10000	0	0
p38alpha-beta/CK2	-0.003	0.052	0.25	10	-0.4	3	13
CEBPB	0	0.048	0.21	10	-0.28	7	17
SLC9A1	0.001	0.043	0.21	10	-0.33	3	13
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	0.005	0.06	0.26	24	-0.33	3	27
p38alpha-beta/MNK1	-0.004	0.044	0.22	10	-0.32	3	13
JUN	0.005	0.076	0.44	14	-0.38	2	16
PPARGC1A	0.003	0.047	0.21	10	-0.33	3	13
USF1	0.002	0.045	0.21	10	-0.33	3	13
RAB5/GDP/GDI1	-0.005	0.024	-10000	0	-0.24	3	3
NOS2	0.002	0.043	0.21	10	-0.33	3	13
DDIT3	0.02	0.071	0.27	11	-0.33	3	14
RAB5A	-0.006	0	-10000	0	-10000	0	0
HSPB1	-0.005	0.039	-10000	0	-0.27	3	3
p38alpha-beta/HBP1	0.002	0.053	0.22	10	-0.32	3	13
CREB1	0.004	0.044	0.21	10	-0.36	3	13
RAB5/GDP	-0.003	0	-10000	0	-10000	0	0
EIF4E	-0.007	0.033	-10000	0	-0.28	3	3
RPS6KA4	0.001	0.043	0.21	10	-0.33	3	13
PLA2G4A	-0.088	0.092	0.16	11	-0.34	4	15
GDI1	0.001	0.046	0.21	10	-0.3	5	15
TP53	-0.001	0.05	0.23	9	-0.45	3	12
RPS6KA5	0.001	0.043	0.21	10	-0.33	3	13
ESR1	-0.029	0.09	0.21	8	-0.24	76	84
HBP1	0.003	0.046	0.24	20	-10000	0	20
MEF2C	-0.007	0.065	0.21	10	-0.27	21	31
MEF2A	0.001	0.043	0.21	10	-0.33	3	13
EIF4EBP1	0.004	0.044	0.21	10	-0.36	3	13
KRT19	-0.01	0.067	0.21	10	-0.25	30	40
ELK4	0.001	0.043	0.21	10	-0.33	3	13
ATF6	0.001	0.043	0.21	10	-0.33	3	13
ATF1	0.004	0.044	0.21	10	-0.36	3	13
p38alpha-beta/MAPKAPK2	-0.004	0.044	0.22	10	-0.32	3	13
p38alpha-beta/MAPKAPK3	-0.004	0.044	0.22	10	-0.32	3	13

×

Calcium signaling in the CD4+ TCR 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
NFATC1	-0.007	0.034	0.2	2	-0.18	9	11
NFATC2	-0.014	0.048	0.2	2	-0.18	31	33
NFATC3	-0.007	0.034	0.2	2	-0.18	8	10
CD40LG	-0.03	0.11	0.46	6	-10000	0	6
PTGS2	-0.028	0.12	0.5	13	-0.44	1	14
JUNB	-0.077	0.13	-10000	0	-0.31	135	135
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.01	0.026	-10000	0	-0.2	11	11
CaM/Ca2+	-0.01	0.026	-10000	0	-0.2	11	11
CALM1	-0.01	0.039	-10000	0	-0.31	9	9
JUN	0	0.042	0.24	14	-0.31	1	15
mol:Ca2+	0	0.007	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	-0.002	0.005	-10000	0	-10000	0	0
FOSL1	-0.006	0	-10000	0	-10000	0	0
CREM	-0.005	0.01	0.24	1	-10000	0	1
Jun/NFAT1-c-4/p21SNFT	-0.017	0.073	0.25	29	-10000	0	29
FOS	-0.026	0.11	0.24	26	-0.31	58	84
IFNG	-0.02	0.14	0.5	20	-10000	0	20
AP-1/NFAT1-c-4	-0.027	0.13	0.54	6	-10000	0	6
FASLG	-0.03	0.11	0.46	6	-10000	0	6
NFAT1-c-4/ICER1	-0.018	0.058	0.21	5	-10000	0	5
IL2RA	-0.028	0.12	0.49	11	-10000	0	11
FKBP12/FK506	-0.003	0	-10000	0	-10000	0	0
CSF2	-0.03	0.11	0.46	6	-10000	0	6
JunB/Fra1/NFAT1-c-4	-0.05	0.08	0.2	5	-0.28	18	23
IL4	-0.03	0.11	0.46	6	-10000	0	6
IL2	-0.004	0.005	-10000	0	-10000	0	0
IL3	-0.008	0.009	-10000	0	-10000	0	0
FKBP1A	-0.006	0	-10000	0	-10000	0	0
BATF3	0	0	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	-0.006	0	-10000	0	-10000	0	0

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.007	0.054	-10000	0	-0.25	11	11
IKBKB	-0.001	0.041	-10000	0	-10000	0	0
AKT1	-0.029	0.059	0.17	5	-0.17	14	19
IKBKG	-0.004	0.035	-10000	0	-10000	0	0
CALM1	-0.011	0.051	-10000	0	-0.23	17	17
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
MAP3K1	-0.01	0.074	0.21	1	-0.36	13	14
MAP3K7	-0.003	0.025	0.24	6	-10000	0	6
mol:Ca2+	-0.007	0.05	-10000	0	-0.24	16	16
DOK1	-0.007	0.018	-10000	0	-0.31	2	2
AP-1	-0.01	0.047	0.17	4	-0.18	8	12
LYN	-0.014	0.048	-10000	0	-0.31	15	15
BLNK	-0.014	0.048	-10000	0	-0.31	15	15
SHC1	-0.006	0	-10000	0	-10000	0	0
BCR complex	-0.004	0.02	0.17	7	-10000	0	7
CD22	-0.054	0.095	0.22	3	-0.34	19	22
CAMK2G	-0.013	0.048	-10000	0	-0.22	17	17
CSNK2A1	-0.006	0	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.022	0.033	-10000	0	-0.26	3	3
GO:0007205	-0.007	0.051	-10000	0	-0.24	16	16
SYK	-0.008	0.034	0.24	2	-0.31	6	8
ELK1	-0.009	0.048	-10000	0	-0.23	16	16
NFATC1	-0.01	0.058	0.19	1	-0.26	15	16
B-cell antigen/BCR complex	-0.004	0.02	0.17	7	-10000	0	7
PAG1/CSK	-0.007	0.007	0.17	1	-10000	0	1
NFKBIB	0	0.021	-10000	0	-0.13	9	9
HRAS	-0.01	0.045	-10000	0	-0.22	15	15
NFKBIA	0.001	0.019	-10000	0	-0.12	6	6
NF-kappa-B/RelA/I kappa B beta	0	0.02	-10000	0	-0.13	8	8
RasGAP/Csk	0.021	0.038	0.28	2	-0.15	4	6
mol:GDP	-0.007	0.049	-10000	0	-0.23	16	16
PTEN	-0.012	0.042	-10000	0	-0.31	11	11
CD79B	-0.006	0	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha	0.001	0.019	-10000	0	-0.12	8	8
GRB2	-0.006	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.072	0.13	0.22	1	-0.34	59	60
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
mol:IP3	-0.007	0.051	-10000	0	-0.24	16	16
CSK	-0.006	0	-10000	0	-10000	0	0
FOS	-0.019	0.068	-10000	0	-0.25	21	21
CHUK	0	0.04	0.18	1	-10000	0	1
IBTK	-0.001	0.036	0.24	12	-10000	0	12
CARD11/BCL10/MALT1/TAK1	0.002	0.055	0.17	4	-0.21	15	19
PTPN6	-0.053	0.091	0.2	3	-0.33	19	22
RELA	-0.006	0.013	-10000	0	-0.31	1	1
BCL2A1	0	0.018	0.093	1	-0.13	2	3
VAV2	-0.011	0.076	0.23	1	-0.35	16	17
ubiquitin-dependent protein catabolic process	0	0.021	-10000	0	-0.13	8	8
BTK	0.008	0.032	-10000	0	-10000	0	0
CD19	-0.01	0.075	0.22	3	-0.36	14	17
MAP4K1	-0.005	0.015	0.24	2	-10000	0	2
CD72	-0.006	0	-10000	0	-10000	0	0
PAG1	-0.005	0.01	0.24	1	-10000	0	1
MAPK14	-0.01	0.067	0.2	1	-0.31	13	14
SH3BP5	-0.007	0.022	-10000	0	-0.31	3	3
PIK3AP1	-0.009	0.055	-10000	0	-0.27	16	16
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.01	0.062	-10000	0	-0.29	21	21
RAF1	-0.011	0.043	-10000	0	-0.21	15	15
RasGAP/p62DOK/SHIP	0.008	0.035	-10000	0	-0.14	6	6
CD79A	-0.003	0.027	0.24	7	-10000	0	7
re-entry into mitotic cell cycle	-0.01	0.046	0.16	4	-0.18	8	12
RASA1	-0.007	0.022	-10000	0	-0.31	3	3
MAPK3	-0.016	0.041	-10000	0	-0.25	3	3
MAPK1	-0.013	0.038	-10000	0	-0.25	3	3
CD72/SHP1	-0.053	0.087	0.19	3	-0.32	19	22
NFKB1	-0.01	0.033	-10000	0	-0.31	7	7
MAPK8	-0.009	0.065	0.2	1	-0.31	10	11
actin cytoskeleton organization	-0.012	0.069	0.22	1	-0.32	16	17
NF-kappa-B/RelA	-0.001	0.047	-10000	0	-0.25	10	10
Calcineurin	-0.015	0.046	-10000	0	-0.21	17	17
PI3K	-0.069	0.073	-10000	0	-0.25	39	39
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.009	0.056	-10000	0	-0.28	16	16
SOS1	0.005	0.05	0.24	24	-10000	0	24
Bam32/HPK1	-0.006	0.086	-10000	0	-0.44	13	13
DAPP1	-0.008	0.093	-10000	0	-0.49	13	13
cytokine secretion	-0.009	0.056	0.19	1	-0.25	15	16
mol:DAG	-0.007	0.051	-10000	0	-0.24	16	16
PLCG2	-0.006	0	-10000	0	-10000	0	0
MAP2K1	-0.012	0.041	-10000	0	-0.27	3	3
B-cell antigen/BCR complex/FcgammaRIIB	0.018	0.037	0.16	37	-0.18	1	38
mol:PI-3-4-5-P3	-0.044	0.067	0.18	4	-0.2	20	24
ETS1	-0.012	0.048	0.16	1	-0.2	17	18
B-cell antigen/BCR complex/LYN/SYK/BLNK	0.005	0.046	-10000	0	-0.16	33	33
B-cell antigen/BCR complex/LYN	-0.013	0.074	0.21	2	-0.37	14	16
MALT1	0.011	0.062	0.24	38	-10000	0	38
TRAF6	-0.005	0.015	0.24	2	-10000	0	2
RAC1	-0.013	0.072	0.22	1	-0.33	16	17
B-cell antigen/BCR complex/LYN/SYK	-0.06	0.073	-10000	0	-0.27	19	19
CARD11	-0.009	0.049	-10000	0	-0.23	16	16
FCGR2B	0.008	0.06	0.24	34	-0.31	1	35
PPP3CA	-0.008	0.025	-10000	0	-0.31	4	4
BCL10	-0.006	0	-10000	0	-10000	0	0
IKK complex	0.001	0.022	0.1	2	-10000	0	2
PTPRC	-0.004	0.11	0.24	53	-0.31	41	94
PDPK1	-0.03	0.055	0.16	5	-0.15	16	21
PPP3CB	-0.006	0	-10000	0	-10000	0	0
PPP3CC	-0.006	0	-10000	0	-10000	0	0
POU2F2	-0.002	0.015	-10000	0	-0.13	2	2

×

Noncanonical Wnt signaling 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
NFATC2	-0.018	0.06	-10000	0	-0.31	23	23
GNB1/GNG2	0.016	0.05	0.18	10	-10000	0	10
mol:DAG	0.013	0.048	0.18	11	-10000	0	11
PLCG1	0.014	0.049	0.18	11	-10000	0	11
YES1	0.024	0.06	0.22	18	-0.18	5	23
FZD3	0.013	0.074	0.24	48	-0.31	4	52
FZD6	0.008	0.059	0.24	33	-0.31	1	34
G protein	0.013	0.049	0.18	10	-10000	0	10
MAP3K7	0.009	0.045	0.17	15	-10000	0	15
mol:Ca2+	0.013	0.047	0.18	11	-10000	0	11
mol:IP3	0.013	0.048	0.18	11	-10000	0	11
NLK	0.007	0.012	-10000	0	-10000	0	0
GNB1	-0.006	0.013	-10000	0	-0.31	1	1
CAMK2A	0.011	0.045	0.17	11	-10000	0	11
MAP3K7IP1	-0.006	0	-10000	0	-10000	0	0
Noncanonical Wnts/FZD	0.021	0.055	0.22	10	-0.18	5	15
CSNK1A1	-0.005	0.015	0.24	2	-10000	0	2
GNAS	0.017	0.052	0.2	10	-0.18	5	15
GO:0007205	0.014	0.047	0.18	11	-10000	0	11
WNT6	-0.006	0	-10000	0	-10000	0	0
WNT4	-0.006	0	-10000	0	-10000	0	0
NFAT1/CK1 alpha	0.012	0.059	0.19	17	-10000	0	17
GNG2	-0.005	0.01	0.24	1	-10000	0	1
WNT5A	-0.003	0.025	0.24	6	-10000	0	6
WNT11	0.016	0.07	0.24	50	-10000	0	50
CDC42	0.02	0.057	0.21	18	-10000	0	18

×

S1P1 pathway

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
VEGFR2 homodimer/VEGFA homodimer	0.005	0.059	0.18	50	-0.24	6	56
PDGFRB	-0.007	0.035	-10000	0	-0.31	7	7
SPHK1	0	0.01	-10000	0	-10000	0	0
mol:S1P	0	0.022	0.28	1	-10000	0	1
S1P1/S1P/Gi	0.02	0.083	0.39	11	-0.47	4	15
GNAO1	-0.001	0.029	0.24	6	-0.31	1	7
PDGFB-D/PDGFRB/PLCgamma1	0.014	0.079	0.33	13	-0.45	4	17
PLCG1	0.017	0.08	0.35	13	-0.44	4	17
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.007	0.035	-10000	0	-0.31	7	7
GNAI2	-0.003	0.008	-10000	0	-10000	0	0
GNAI3	0.037	0.092	0.24	96	-10000	0	96
GNAI1	-0.002	0.041	0.24	8	-0.31	5	13
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	0.001	0.065	0.26	2	-0.43	6	8
S1P1/S1P	0.009	0.066	0.26	7	-0.38	6	13
negative regulation of cAMP metabolic process	0.02	0.082	0.38	11	-0.46	4	15
MAPK3	0.014	0.095	0.45	11	-0.59	4	15
calcium-dependent phospholipase C activity	0	0.003	-10000	0	-10000	0	0
Rac1/GDP	-0.004	0.009	-10000	0	-0.21	1	1
RhoA/GDP	-0.004	0.012	-10000	0	-0.21	2	2
KDR	-0.008	0.021	0.24	2	-0.15	6	8
PLCB2	0.006	0.061	0.24	7	-0.35	6	13
RAC1	-0.006	0.013	-10000	0	-0.31	1	1
RhoA/GTP	-0.009	0.037	-10000	0	-0.33	6	6
receptor internalization	0.008	0.062	0.22	15	-0.36	6	21
PTGS2	0.014	0.11	0.53	11	-0.99	3	14
Rac1/GTP	-0.009	0.037	-10000	0	-0.33	6	6
RHOA	-0.007	0.018	-10000	0	-0.31	2	2
VEGFA	0.013	0.072	0.24	49	-10000	0	49
negative regulation of T cell proliferation	0.02	0.082	0.38	11	-0.46	4	15
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	-0.005	0.027	-10000	0	-0.31	4	4
MAPK1	0.017	0.094	0.45	11	-0.59	4	15
S1P1/S1P/PDGFB-D/PDGFRB	0.01	0.076	0.26	14	-0.4	7	21
ABCC1	0	0.029	0.24	8	-10000	0	8

×

E-cadherin signaling events

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
E-cadherin/beta catenin-gamma catenin	0.001	0.042	0.16	2	-0.19	24	26
E-cadherin/beta catenin	-0.011	0.032	0.17	2	-0.21	13	15
CTNNB1	-0.005	0.015	0.24	2	-10000	0	2
JUP	-0.013	0.045	-10000	0	-0.31	13	13
CDH1	-0.013	0.045	-10000	0	-0.31	13	13

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	-0.001	0.007	-10000	0	-10000	0	0
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	-0.008	0.051	-10000	0	-0.22	29	29
AP2	-0.018	0.053	0.17	6	-0.21	35	41
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	-0.007	0.008	-10000	0	-0.18	1	1
CLTB	-0.006	0	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	-0.012	0.043	-10000	0	-0.19	29	29
CD4	-0.002	0.036	0.24	11	-0.31	1	12
CLTA	-0.006	0	-10000	0	-10000	0	0
mol:GTP	-0.002	0.005	-10000	0	-10000	0	0
ARFGAP1	-0.003	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.002	0.029	0.11	22	-10000	0	22
ARF1/GTP	-0.013	0.038	-10000	0	-0.18	29	29
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	-0.012	0.037	-10000	0	-0.17	29	29
mol:Choline	-0.002	0.028	0.11	22	-10000	0	22
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	-0.022	0.068	-10000	0	-0.32	29	29
DDEF1	-0.001	0.028	0.11	22	-10000	0	22
ARF1/GDP	0.001	0.007	-10000	0	-10000	0	0
AP2M1	-0.003	0.025	0.24	6	-10000	0	6
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	-0.013	0.034	-10000	0	-0.16	30	30
Rac/GTP	-0.005	0.009	-10000	0	-0.22	1	1
ARF1/GTP/GGA3/ARF-GAP1	-0.014	0.031	-10000	0	-0.15	29	29
ARFIP2	-0.007	0.003	-10000	0	-10000	0	0
COPA	-0.005	0.015	0.24	2	-10000	0	2
RAC1	-0.006	0.013	-10000	0	-0.31	1	1
ARF1/GTP/coatomer protein complex	-0.008	0.04	-10000	0	-0.18	29	29
ARF1/GTP/ARHGAP10	-0.012	0.038	-10000	0	-0.18	29	29
GGA3	-0.006	0	-10000	0	-10000	0	0
ARF1/GTP/Membrin	-0.005	0.035	-10000	0	-0.16	29	29
AP2A1	-0.024	0.073	-10000	0	-0.31	35	35
coatomer protein complex/ARF1/GTP/ARF-GAP1	-0.01	0.037	-10000	0	-0.17	29	29
ARF1/GDP/Membrin	-0.004	0.033	-10000	0	-0.15	29	29
Arfaptin 2/Rac/GDP	0.005	0.008	-10000	0	-0.17	1	1
CYTH2	-0.002	0.005	-10000	0	-10000	0	0
ARF1/GTP/GGA3	-0.015	0.038	-10000	0	-0.18	29	29
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	-0.004	0.009	-10000	0	-0.21	1	1
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	-0.016	0.053	-10000	0	-0.3	4	4
PLD2	-0.002	0.029	0.11	22	-10000	0	22
ARF-GAP1/v-SNARE	-0.003	0	-10000	0	-10000	0	0
PIP5K1A	-0.002	0.029	0.11	22	-10000	0	22
ARF1/GTP/Membrin/GBF1/p115	-0.011	0.035	-10000	0	-0.16	29	29
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.002	0.028	0.11	22	-10000	0	22
KDEL Receptor/Ligand/ARF-GAP1	-0.003	0	-10000	0	-10000	0	0
GOSR2	0.001	0.014	-10000	0	-10000	0	0
USO1	0.002	0.025	0.13	6	-0.37	1	7
GBF1	0	0.026	-10000	0	-0.37	2	2
ARF1/GTP/Arfaptin 2	-0.015	0.038	-10000	0	-0.18	29	29
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.002	0.051	0.16	15	-0.18	34	49

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.006	0.036	0.25	1	-0.16	21	22
KIRREL	-0.003	0.044	0.22	19	-0.34	1	20
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.006	0.036	0.16	21	-0.26	1	22
PLCG1	-0.004	0.023	0.24	5	-10000	0	5
ARRB2	-0.006	0	-10000	0	-10000	0	0
WASL	-0.006	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	0.009	0.034	0.17	6	-0.18	1	7
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.005	0.037	0.2	1	-0.21	1	2
FYN	-0.003	0.025	0.11	20	-0.28	1	21
mol:Ca2+	0.008	0.034	0.16	7	-0.2	1	8
mol:DAG	0.009	0.034	0.16	7	-0.2	1	8
NPHS2	-0.009	0.01	-10000	0	-10000	0	0
mol:IP3	0.009	0.034	0.16	7	-0.2	1	8
regulation of endocytosis	-0.017	0.044	0.13	19	-0.26	1	20
Nephrin/NEPH1/podocin/Cholesterol	0.006	0.032	0.14	21	-0.2	1	22
establishment of cell polarity	-0.006	0.036	0.16	21	-0.25	1	22
Nephrin/NEPH1/podocin/NCK1-2	0.021	0.048	0.17	8	-0.18	1	9
Nephrin/NEPH1/beta Arrestin2	-0.017	0.045	0.13	19	-0.27	1	20
NPHS1	-0.008	0.019	0.22	3	-10000	0	3
Nephrin/NEPH1/podocin	-0.004	0.05	0.14	19	-0.11	77	96
TJP1	-0.005	0.019	0.24	2	-0.31	1	3
NCK1	0.012	0.065	0.24	42	-10000	0	42
NCK2	-0.006	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.009	0.035	0.17	7	-0.2	1	8
CD2AP	-0.004	0.026	0.24	5	-0.31	1	6
Nephrin/NEPH1/podocin/GRB2	0.008	0.033	0.18	3	-0.2	1	4
GRB2	-0.006	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.008	0.028	0.15	4	-0.18	1	5
cytoskeleton organization	-0.001	0.036	0.22	1	-0.22	1	2
Nephrin/NEPH1	0.006	0.028	0.13	21	-0.17	1	22
Nephrin/NEPH1/ZO-1	-0.007	0.033	0.14	21	-0.2	2	23

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	-0.002	0.054	-10000	0	-0.26	19	19
Ran/GTP/Exportin 1/HDAC1	-0.007	0.003	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.021	0.064	-10000	0	-0.31	20	20
SUMO1	-0.006	0	-10000	0	-10000	0	0
ZFPM1	-0.006	0	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	-0.001	0.006	-10000	0	-10000	0	0
FKBP3	-0.001	0.034	0.24	11	-10000	0	11
Histones	0.007	0.059	0.28	7	-10000	0	7
YY1/LSF	0.003	0.054	0.17	38	-0.18	16	54
SMG5	-0.004	0.018	0.24	3	-10000	0	3
RAN	-0.006	0	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	-0.015	0.049	-10000	0	-0.21	28	28
I kappa B alpha/HDAC1	-0.005	0.062	0.16	31	-0.35	8	39
SAP18	-0.006	0.013	-10000	0	-0.31	1	1
RELA	-0.012	0.048	-10000	0	-0.23	14	14
HDAC1/Smad7	0.018	0.036	0.16	36	-10000	0	36
RANGAP1	-0.006	0	-10000	0	-10000	0	0
HDAC3/TR2	-0.009	0.024	0.16	2	-10000	0	2
NuRD/MBD3 Complex	0.005	0.041	0.17	13	-10000	0	13
NF kappa B1 p50/RelA	-0.014	0.049	-10000	0	-0.34	6	6
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	-0.009	0.035	0.24	1	-0.31	7	8
GATA1	-0.006	0	-10000	0	-10000	0	0
Mad/Max	-0.006	0.015	0.17	4	-10000	0	4
NuRD/MBD3 Complex/GATA1/Fog1	0.003	0.041	0.17	13	-10000	0	13
RBBP7	-0.007	0.018	-10000	0	-0.31	2	2
NPC	0.003	0.008	0.13	2	-10000	0	2
RBBP4	0.002	0.043	0.24	18	-10000	0	18
MAX	-0.006	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	-0.006	0	-10000	0	-10000	0	0
NFKBIA	-0.014	0.056	-10000	0	-0.34	13	13
KAT2B	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.007	0.04	0.19	12	-10000	0	12
SIN3 complex	0.011	0.009	-10000	0	-0.16	1	1
SMURF1	-0.006	0	-10000	0	-10000	0	0
CHD3	-0.011	0.04	-10000	0	-0.31	10	10
SAP30	-0.006	0	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	-0.007	0.018	-10000	0	-0.31	2	2
YY1/HDAC3	-0.011	0.032	-10000	0	-0.27	1	1
YY1/HDAC2	-0.005	0.037	0.17	11	-0.19	14	25
YY1/HDAC1	0.003	0.051	0.17	36	-0.19	13	49
NuRD/MBD2 Complex (MeCP1)	0.005	0.041	0.17	13	-10000	0	13
PPARG	-0.012	0.049	-10000	0	-0.24	20	20
HDAC8/hEST1B	0.016	0.032	0.16	29	-10000	0	29
UBE2I	-0.006	0	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	-0.006	0	-10000	0	-10000	0	0
TNFRSF1A	-0.016	0.054	-10000	0	-0.31	19	19
HDAC3/SMRT (N-CoR2)	-0.011	0.028	-10000	0	-10000	0	0
MBD3L2	-0.006	0	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.018	0.036	0.16	36	-10000	0	36
CREBBP	-0.012	0.042	-10000	0	-0.31	11	11
NuRD/MBD3/MBD3L2 Complex	0.003	0.043	0.18	13	-10000	0	13
HDAC1	0.01	0.06	0.24	36	-10000	0	36
HDAC3	-0.008	0.025	-10000	0	-10000	0	0
HDAC2	-0.002	0.036	0.24	11	-0.31	1	12
YY1	-0.006	0.032	-10000	0	-0.22	13	13
HDAC8	0.006	0.052	0.24	26	-10000	0	26
SMAD7	-0.006	0	-10000	0	-10000	0	0
NCOR2	-0.011	0.038	-10000	0	-0.31	9	9
MXD1	-0.004	0.021	0.24	4	-10000	0	4
STAT3	-0.012	0.05	-10000	0	-0.26	22	22
NFKB1	-0.01	0.033	-10000	0	-0.31	7	7
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	-0.005	0.015	0.24	2	-10000	0	2
YY1/LSF/HDAC1	0.01	0.067	0.17	66	-0.17	16	82
YY1/SAP30/HDAC1	0.001	0.047	0.15	36	-0.17	13	49
EP300	-0.007	0.018	-10000	0	-0.31	2	2
STAT3 (dimer non-phopshorylated)	-0.012	0.05	-10000	0	-0.25	22	22
proteasomal ubiquitin-dependent protein catabolic process	-0.014	0.056	-10000	0	-0.34	13	13
histone deacetylation	0.005	0.04	0.17	13	-10000	0	13
STAT3 (dimer non-phopshorylated)/HDAC3	-0.015	0.042	-10000	0	-0.34	2	2
nuclear export	-0.016	0.032	-10000	0	-0.16	29	29
PRKACA	-0.006	0	-10000	0	-10000	0	0
GATAD2B	-0.006	0.013	-10000	0	-0.31	1	1
GATAD2A	-0.005	0.01	0.24	1	-10000	0	1
GATA2/HDAC3	-0.011	0.028	0.16	1	-10000	0	1
GATA1/HDAC1	0.004	0.043	0.17	36	-10000	0	36
GATA1/HDAC3	-0.009	0.022	-10000	0	-10000	0	0
CHD4	-0.005	0.01	0.24	1	-10000	0	1
TNF-alpha/TNFR1A	-0.013	0.038	0.17	1	-0.21	19	20
SIN3/HDAC complex/Mad/Max	0.008	0.037	0.21	4	-10000	0	4
NuRD Complex	0.003	0.043	0.18	13	-10000	0	13
positive regulation of chromatin silencing	0.007	0.057	0.27	7	-10000	0	7
SIN3B	-0.005	0.01	0.24	1	-10000	0	1
MTA2	-0.006	0	-10000	0	-10000	0	0
SIN3A	-0.006	0	-10000	0	-10000	0	0
XPO1	0.014	0.068	0.24	46	-10000	0	46
SUMO1/HDAC1	0.014	0.036	0.15	36	-10000	0	36
HDAC complex	0.026	0.054	0.29	11	-0.16	3	14
GATA1/Fog1	-0.007	0	-10000	0	-10000	0	0
FKBP25/HDAC1/HDAC2	0.023	0.043	0.16	53	-10000	0	53
TNF	-0.005	0.01	0.24	1	-10000	0	1
negative regulation of cell growth	0.008	0.037	0.21	4	-10000	0	4
NuRD/MBD2/PRMT5 Complex	0.005	0.041	0.17	13	-10000	0	13
Ran/GTP/Exportin 1	0.007	0.039	0.14	46	-10000	0	46
NF kappa B/RelA/I kappa B alpha	-0.018	0.061	-10000	0	-0.3	20	20
SIN3/HDAC complex/NCoR1	0.007	0.039	0.19	12	-10000	0	12
TFCP2	0.009	0.066	0.24	38	-0.31	3	41
NR2C1	-0.005	0.015	0.24	2	-10000	0	2
MBD3	-0.006	0	-10000	0	-10000	0	0
MBD2	-0.006	0	-10000	0	-10000	0	0

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	-0.006	0	-10000	0	-10000	0	0
SPHK1	-0.005	0.01	0.24	1	-10000	0	1
GNAI2	-0.006	0	-10000	0	-10000	0	0
mol:S1P	0.001	0.017	0.14	9	-10000	0	9
GNAO1	-0.004	0.028	0.24	6	-0.31	1	7
mol:Sphinganine-1-P	-0.007	0.009	0.2	1	-10000	0	1
growth factor activity	0	0	-10000	0	-10000	0	0
S1P/S1P2/G12/G13	-0.004	0.013	-10000	0	-10000	0	0
GNAI3	0.036	0.093	0.24	96	-10000	0	96
G12/G13	-0.007	0.009	-10000	0	-0.21	1	1
S1PR3	0	0	-10000	0	-10000	0	0
S1PR2	0	0	-10000	0	-10000	0	0
EDG1	-0.009	0.031	-10000	0	-0.31	6	6
S1P1/S1P	-0.004	0.021	-10000	0	-0.17	6	6
S1PR5	0	0	-10000	0	-10000	0	0
S1PR4	0	0	-10000	0	-10000	0	0
GNAI1	-0.005	0.041	0.24	8	-0.31	5	13
S1P/S1P5/G12	-0.003	0	-10000	0	-10000	0	0
S1P/S1P3/Gq	-0.019	0.066	-10000	0	-0.2	60	60
S1P/S1P4/Gi	0.014	0.043	0.18	2	-0.18	6	8
GNAQ	-0.012	0.043	-10000	0	-0.31	12	12
GNAZ	-0.008	0.025	-10000	0	-0.31	4	4
GNA14	-0.005	0.015	0.24	2	-10000	0	2
GNA15	-0.006	0.016	0.24	1	-0.31	1	2
GNA12	-0.006	0	-10000	0	-10000	0	0
GNA13	-0.006	0.013	-10000	0	-0.31	1	1
GNA11	-0.034	0.088	-10000	0	-0.31	53	53
ABCC1	-0.002	0.029	0.24	8	-10000	0	8

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.012	0.14	0.49	2	-0.48	2	4
CRKL	-0.027	0.041	0.21	2	-10000	0	2
mol:DAG	-0.036	0.067	0.27	2	-0.33	4	6
HRAS	-0.027	0.041	0.22	1	-10000	0	1
MAPK8	-0.018	0.031	0.16	4	-0.17	12	16
RAP1A	-0.027	0.041	0.21	2	-10000	0	2
GAB1	-0.028	0.041	0.21	2	-10000	0	2
MAPK14	-0.02	0.033	0.36	1	-0.17	15	16
EPO	-0.01	0.009	-10000	0	-10000	0	0
PLCG1	-0.037	0.068	0.27	2	-0.34	4	6
EPOR/TRPC2/IP3 Receptors	-0.01	0.014	0.26	1	-10000	0	1
RAPGEF1	-0.006	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.012	0.019	0.17	3	-0.2	2	5
GAB1/SHC/GRB2/SOS1	-0.025	0.043	-10000	0	-10000	0	0
EPO/EPOR (dimer)	-0.012	0.016	0.24	1	-10000	0	1
IRS2	-0.027	0.041	0.21	2	-10000	0	2
STAT1	0.029	0.12	0.4	2	-0.37	4	6
STAT5B	-0.051	0.093	0.34	2	-0.39	7	9
cell proliferation	-0.019	0.03	0.18	4	-0.16	12	16
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.058	0.06	-10000	0	-0.22	21	21
TEC	-0.016	0.057	0.29	2	-10000	0	2
SOCS3	-0.006	0.023	0.24	2	-0.31	2	4
STAT1 (dimer)	0.029	0.12	0.39	2	-0.37	4	6
JAK2	-0.01	0.023	0.22	2	-0.31	2	4
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
EPO/EPOR (dimer)/JAK2	-0.026	0.048	0.39	2	-10000	0	2
EPO/EPOR	-0.012	0.016	0.24	1	-10000	0	1
LYN	-0.017	0.049	-10000	0	-0.31	15	15
TEC/VAV2	-0.018	0.056	0.29	2	-10000	0	2
elevation of cytosolic calcium ion concentration	-0.01	0.014	0.26	1	-10000	0	1
SHC1	-0.006	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	-0.02	0.037	0.26	2	-0.19	15	17
mol:IP3	-0.036	0.067	0.27	2	-0.33	4	6
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.056	0.064	0.14	1	-0.23	21	22
SH2B3	-0.01	0.007	-10000	0	-10000	0	0
NFKB1	-0.022	0.039	0.19	1	-0.21	17	18
EPO/EPOR (dimer)/JAK2/SOCS3	-0.003	0.016	-10000	0	-0.18	3	3
PTPN6	-0.026	0.043	0.22	2	-10000	0	2
TEC/VAV2/GRB2	-0.019	0.054	0.28	2	-10000	0	2
EPOR	-0.01	0.014	0.26	1	-10000	0	1
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	-0.026	0.042	-10000	0	-10000	0	0
SOS1	0.005	0.05	0.24	24	-10000	0	24
PLCG2	-0.006	0	-10000	0	-10000	0	0
CRKL/CBL/C3G	-0.029	0.039	0.22	2	-10000	0	2
VAV2	-0.028	0.042	0.21	2	-10000	0	2
CBL	-0.027	0.041	0.21	2	-10000	0	2
SHC/Grb2/SOS1	-0.028	0.035	0.15	1	-10000	0	1
STAT5A	-0.05	0.092	0.34	2	-0.38	7	9
GRB2	-0.006	0	-10000	0	-10000	0	0
STAT5 (dimer)	-0.075	0.14	0.46	2	-0.38	66	68
LYN/PLCgamma2	-0.014	0.033	-10000	0	-0.21	15	15
PTPN11	-0.006	0	-10000	0	-10000	0	0
BTK	-0.021	0.052	0.22	3	-10000	0	3
BCL2	-0.085	0.29	0.49	2	-0.72	93	95

×

Signaling events mediated by HDAC Class III

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
EP300	-0.007	0.018	-10000	0	-0.31	2	2
HDAC4	-0.006	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.001	0.019	-10000	0	-0.12	14	14
CDKN1A	-0.005	0.093	-10000	0	-0.52	16	16
KAT2B	0	0	-10000	0	-10000	0	0
BAX	-0.006	0	-10000	0	-10000	0	0
FOXO3	0	0.026	0.3	2	-0.16	8	10
FOXO1	-0.009	0.031	-10000	0	-0.31	6	6
FOXO4	-0.006	0.032	-10000	0	-0.22	13	13
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	-0.006	0	-10000	0	-10000	0	0
TAT	-0.006	0	-10000	0	-10000	0	0
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.003	0	-10000	0	-10000	0	0
PPARGC1A	-0.003	0.025	0.24	6	-10000	0	6
FHL2	-0.005	0.015	0.24	2	-10000	0	2
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	-0.004	0.02	-10000	0	-10000	0	0
HIST2H4A	-0.001	0.019	0.12	14	-10000	0	14
SIRT1/FOXO3a	-0.002	0.027	0.21	2	-10000	0	2
SIRT1	-0.003	0.027	0.16	14	-10000	0	14
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.009	0.018	-10000	0	-10000	0	0
SIRT1/Histone H1b	-0.004	0.036	-10000	0	-0.19	13	13
apoptosis	0.006	0.019	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.001	0.024	0.12	20	-10000	0	20
p53/SIRT1	-0.031	0.092	0.32	15	-0.22	83	98
SIRT1/FOXO4	-0.005	0.034	-10000	0	-0.19	13	13
FOXO1/FHL2/SIRT1	0.01	0.024	0.15	2	-0.16	5	7
HIST1H1E	-0.005	0.036	0.14	8	-0.22	13	21
SIRT1/p300	-0.005	0.024	-10000	0	-0.21	2	2
muscle cell differentiation	0.003	0.018	-10000	0	-0.11	14	14
TP53	-0.047	0.11	0.17	15	-0.31	83	98
KU70/SIRT1/BAX	0.009	0.018	-10000	0	-10000	0	0
CREBBP	-0.012	0.042	-10000	0	-0.31	11	11
MEF2D	-0.006	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.004	0.02	-10000	0	-10000	0	0
ACSS2	-0.005	0.022	-10000	0	-0.21	1	1
SIRT1/PCAF/MYOD	-0.003	0.018	0.11	14	-10000	0	14

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	-0.015	0.034	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP1	-0.006	0.012	-10000	0	-10000	0	0
mol:DAG	-0.009	0.019	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	0.006	0.046	-10000	0	-10000	0	0
CaM/Ca2+	-0.013	0.026	-10000	0	-10000	0	0
HIF1A	-0.01	0.022	-10000	0	-0.31	3	3
GAB1	-0.007	0.018	-10000	0	-0.31	2	2
AKT1	-0.025	0.089	-10000	0	-0.3	2	2
PLCG1	-0.009	0.019	-10000	0	-10000	0	0
NOS3	-0.015	0.046	-10000	0	-10000	0	0
CBL	-0.006	0	-10000	0	-10000	0	0
mol:NO	-0.015	0.045	-10000	0	-10000	0	0
FLT1	-0.008	0.015	-10000	0	-10000	0	0
PGF	-0.006	0.013	-10000	0	-0.31	1	1
VEGFR1 homodimer/NRP2/VEGFR121	0.012	0.059	0.3	3	-10000	0	3
CALM1	-0.012	0.042	-10000	0	-0.31	11	11
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
eNOS/Hsp90	-0.016	0.045	-10000	0	-10000	0	0
endothelial cell proliferation	-0.011	0.028	0.22	1	-10000	0	1
mol:Ca2+	-0.009	0.019	-10000	0	-10000	0	0
MAPK3	-0.015	0.034	0.24	1	-0.28	1	2
MAPK1	-0.012	0.027	0.24	1	-10000	0	1
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
PLGF homodimer	-0.006	0.013	-10000	0	-0.31	1	1
PRKACA	-0.006	0	-10000	0	-10000	0	0
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	-0.053	0.11	0.24	2	-0.31	90	92
VEGFA homodimer	0.015	0.069	0.24	49	-10000	0	49
VEGFR1 homodimer/VEGFA homodimer	0.006	0.051	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	-0.016	0.033	0.23	1	-0.27	1	2
PI3K	-0.012	0.091	-10000	0	-0.29	2	2
PRKCA	-0.01	0.027	0.27	1	-10000	0	1
PRKCB	-0.008	0.017	-10000	0	-10000	0	0
VEGFR1 homodimer/PLGF homodimer	-0.009	0.014	-10000	0	-10000	0	0
VEGFA	0.016	0.069	0.24	49	-10000	0	49
VEGFB	-0.017	0.057	-10000	0	-0.31	21	21
mol:IP3	-0.009	0.019	-10000	0	-10000	0	0
RASA1	-0.017	0.032	-10000	0	-10000	0	0
NRP2	0.006	0.054	0.24	28	-10000	0	28
VEGFR1 homodimer	-0.008	0.015	-10000	0	-10000	0	0
VEGFB homodimer	-0.017	0.057	-10000	0	-0.31	21	21
NCK1	0.012	0.065	0.24	42	-10000	0	42
eNOS/Caveolin-1	-0.033	0.069	-10000	0	-0.36	3	3
PTPN11	-0.006	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.012	0.09	-10000	0	-0.29	2	2
mol:L-citrulline	-0.015	0.045	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.003	0.049	0.29	1	-10000	0	1
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.016	0.064	0.3	4	-10000	0	4
CD2AP	-0.004	0.026	0.24	5	-0.31	1	6
PI3K/GAB1	-0.014	0.088	-10000	0	-0.28	2	2
PDPK1	-0.017	0.078	-10000	0	-0.27	2	2
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.004	0.047	-10000	0	-10000	0	0
mol:NADP	-0.015	0.045	-10000	0	-10000	0	0
HSP90AA1	-0.006	0.013	-10000	0	-0.31	1	1
ubiquitin-dependent protein catabolic process	0.003	0.048	0.28	1	-10000	0	1
VEGFR1 homodimer/NRP2	0	0.04	-10000	0	-10000	0	0

×

Angiopoietin receptor Tie2-mediated signaling

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
AKT1	-0.028	0.097	0.77	2	-10000	0	2
NCK1/PAK1/Dok-R	-0.028	0.043	-10000	0	-10000	0	0
NCK1/Dok-R	0.003	0.05	-10000	0	-10000	0	0
PIK3CA	0.047	0.1	0.24	122	-10000	0	122
mol:beta2-estradiol	-0.001	0.018	-10000	0	-0.16	7	7
RELA	-0.006	0.013	-10000	0	-0.31	1	1
SHC1	-0.003	0.006	-10000	0	-10000	0	0
Rac/GDP	-0.004	0.009	-10000	0	-0.21	1	1
F2	0.003	0.027	0.25	1	-0.19	7	8
TNIP2	-0.005	0.01	0.24	1	-10000	0	1
NF kappa B/RelA	-0.014	0.027	-10000	0	-10000	0	0
FN1	0.075	0.13	0.24	200	-0.31	12	212
PLD2	-0.005	0.044	0.72	1	-10000	0	1
PTPN11	-0.006	0	-10000	0	-10000	0	0
GRB14	0.006	0.052	0.24	26	-10000	0	26
ELK1	-0.009	0.043	0.65	1	-10000	0	1
GRB7	-0.006	0.03	0.24	4	-0.31	3	7
PAK1	0.002	0.043	0.24	18	-10000	0	18
Tie2/Ang1/alpha5/beta1 Integrin	0.041	0.088	0.41	1	-10000	0	1
CDKN1A	-0.031	0.14	0.77	2	-0.74	16	18
ITGA5	-0.003	0.025	0.24	6	-10000	0	6
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.009	0.033	-10000	0	-10000	0	0
CRK	-0.005	0.01	0.24	1	-10000	0	1
mol:NO	-0.026	0.087	0.49	6	-10000	0	6
PLG	-0.009	0.048	0.72	1	-10000	0	1
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.012	0.078	0.69	2	-10000	0	2
GRB2	-0.006	0	-10000	0	-10000	0	0
PIK3R1	-0.075	0.13	-10000	0	-0.31	131	131
ANGPT2	-0.005	0.07	0.58	6	-10000	0	6
BMX	-0.005	0.044	0.72	1	-10000	0	1
ANGPT1	0.003	0.051	0.58	2	-10000	0	2
tube development	-0.036	0.1	0.56	6	-10000	0	6
ANGPT4	-0.006	0.005	-10000	0	-10000	0	0
response to hypoxia	-0.001	0.006	0.11	1	-10000	0	1
Tie2/Ang1/GRB14	0.002	0.054	0.65	1	-10000	0	1
alpha5/beta1 Integrin	-0.003	0.025	0.17	12	-10000	0	12
FGF2	-0.011	0.04	-10000	0	-0.31	10	10
STAT5A (dimer)	-0.031	0.12	0.77	2	-0.65	2	4
mol:L-citrulline	-0.026	0.087	0.49	6	-10000	0	6
AGTR1	-0.005	0.007	-10000	0	-10000	0	0
MAPK14	-0.006	0.056	0.84	1	-10000	0	1
Tie2/SHP2	-0.007	0.027	-10000	0	-10000	0	0
TEK	-0.004	0.044	0.73	1	-10000	0	1
RPS6KB1	-0.024	0.095	0.72	2	-10000	0	2
Angiotensin II/AT1	-0.002	0.015	0.14	6	-10000	0	6
Tie2/Ang1/GRB2	-0.006	0.042	0.65	1	-10000	0	1
MAPK3	-0.011	0.046	0.66	1	-10000	0	1
MAPK1	-0.007	0.042	0.66	1	-10000	0	1
Tie2/Ang1/GRB7	-0.007	0.03	-10000	0	-10000	0	0
NFKB1	-0.01	0.033	-10000	0	-0.31	7	7
MAPK8	-0.004	0.046	0.72	1	-10000	0	1
PI3K	-0.026	0.099	0.76	2	-10000	0	2
FES	-0.007	0.057	0.85	1	-10000	0	1
Crk/Dok-R	-0.008	0.032	-10000	0	-10000	0	0
Tie2/Ang1/ABIN2	-0.005	0.042	0.65	1	-10000	0	1
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.027	0.094	0.76	2	-10000	0	2
STAT5A	-0.01	0.036	-10000	0	-0.31	8	8
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.021	0.099	0.72	2	-10000	0	2
Tie2/Ang2	-0.023	0.1	0.83	2	-10000	0	2
Tie2/Ang1	-0.003	0.049	0.83	1	-10000	0	1
FOXO1	-0.031	0.097	0.78	2	-10000	0	2
ELF1	-0.008	0.027	0.2	1	-0.31	4	5
ELF2	-0.003	0.047	0.8	1	-10000	0	1
mol:Choline	-0.005	0.044	0.72	1	-10000	0	1
cell migration	-0.016	0.026	-10000	0	-10000	0	0
FYN	-0.039	0.1	0.57	6	-10000	0	6
DOK2	-0.005	0.01	0.24	1	-10000	0	1
negative regulation of cell cycle	-0.028	0.13	0.56	5	-0.66	16	21
ETS1	-0.001	0.037	0.22	15	-10000	0	15
PXN	-0.022	0.094	0.69	2	-10000	0	2
ITGB1	-0.003	0.025	0.24	6	-10000	0	6
NOS3	-0.028	0.091	0.73	2	-10000	0	2
RAC1	-0.006	0.013	-10000	0	-0.31	1	1
TNF	-0.004	0.021	0.17	8	-10000	0	8
MAPKKK cascade	-0.005	0.044	0.72	1	-10000	0	1
RASA1	-0.007	0.022	-10000	0	-0.31	3	3
Tie2/Ang1/Shc	-0.004	0.044	0.69	1	-10000	0	1
NCK1	0.012	0.065	0.24	42	-10000	0	42
vasculogenesis	-0.024	0.084	0.49	6	-10000	0	6
mol:Phosphatidic acid	-0.005	0.044	0.72	1	-10000	0	1
mol:Angiotensin II	0	0.006	-10000	0	-10000	0	0
mol:NADP	-0.026	0.087	0.49	6	-10000	0	6
Rac1/GTP	-0.032	0.07	-10000	0	-10000	0	0
MMP2	-0.015	0.073	0.72	1	-10000	0	1

×

S1P5 pathway

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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	-0.009	0.038	0.15	6	-10000	0	6
GNAI2	-0.006	0	-10000	0	-10000	0	0
S1P/S1P5/G12	0.003	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.004	0.028	0.24	6	-0.31	1	7
RhoA/GTP	0.009	0.038	-10000	0	-0.15	6	6
negative regulation of cAMP metabolic process	0.014	0.043	0.18	2	-0.17	6	8
GNAZ	-0.008	0.025	-10000	0	-0.31	4	4
GNAI3	0.036	0.093	0.24	96	-10000	0	96
GNA12	-0.006	0	-10000	0	-10000	0	0
S1PR5	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	0.014	0.043	0.18	2	-0.17	6	8
RhoA/GDP	-0.004	0.012	-10000	0	-0.21	2	2
RHOA	-0.007	0.018	-10000	0	-0.31	2	2
GNAI1	-0.005	0.041	0.24	8	-0.31	5	13

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.01	0.019	0.15	1	-0.16	6	7
HDAC3	-0.006	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.007	0.002	-10000	0	-10000	0	0
GATA1/HDAC4	-0.007	0	-10000	0	-10000	0	0
GATA1/HDAC5	-0.009	0.019	-10000	0	-0.21	5	5
GATA2/HDAC5	-0.011	0.03	0.17	1	-0.21	12	13
HDAC5/BCL6/BCoR	0.003	0.034	0.16	1	-0.18	19	20
HDAC9	0.004	0.048	0.24	22	-10000	0	22
Glucocorticoid receptor/Hsp90/HDAC6	0.006	0.029	0.16	5	-0.18	11	16
HDAC4/ANKRA2	-0.007	0.011	0.17	1	-0.21	1	2
HDAC5/YWHAB	-0.008	0.021	0.17	1	-0.21	5	6
NPC/RanGAP1/SUMO1/Ubc9	-0.001	0.006	-10000	0	-10000	0	0
GATA2	-0.009	0.035	0.24	1	-0.31	7	8
HDAC4/RFXANK	-0.006	0.01	0.17	2	-10000	0	2
BCOR	-0.005	0.01	0.24	1	-10000	0	1
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	-0.006	0	-10000	0	-10000	0	0
HDAC5	-0.008	0.028	-10000	0	-0.31	5	5
GNB1/GNG2	-0.007	0.011	0.17	1	-0.21	1	2
Histones	0	0.026	0.18	1	-0.18	4	5
ADRBK1	-0.006	0	-10000	0	-10000	0	0
HDAC4	-0.006	0	-10000	0	-10000	0	0
XPO1	0.014	0.068	0.24	46	-10000	0	46
HDAC5/ANKRA2	-0.009	0.022	0.17	1	-0.21	6	7
HDAC4/Ubc9	-0.007	0	-10000	0	-10000	0	0
HDAC7	0	0	-10000	0	-10000	0	0
HDAC5/14-3-3 E	-0.009	0.021	-10000	0	-0.21	6	6
TUBA1B	-0.006	0	-10000	0	-10000	0	0
HDAC6	-0.004	0.023	0.24	5	-10000	0	5
HDAC5/RFXANK	-0.008	0.022	0.17	2	-0.21	5	7
CAMK4	-0.002	0.031	0.24	9	-10000	0	9
Tubulin/HDAC6	0.01	0.015	0.16	6	-10000	0	6
SUMO1	-0.006	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	-0.005	0.01	0.24	1	-10000	0	1
GATA1	-0.006	0	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	-0.006	0.013	-10000	0	-0.31	1	1
NR3C1	-0.011	0.04	-10000	0	-0.31	10	10
SUMO1/HDAC4	0.005	0	-10000	0	-10000	0	0
SRF	-0.007	0.022	-10000	0	-0.31	3	3
HDAC4/YWHAB	-0.007	0.007	0.17	1	-10000	0	1
Tubulin	-0.007	0.007	0.17	1	-10000	0	1
HDAC4/14-3-3 E	-0.007	0.009	-10000	0	-0.21	1	1
GNB1	-0.006	0.013	-10000	0	-0.31	1	1
RANGAP1	-0.006	0	-10000	0	-10000	0	0
BCL6/BCoR	-0.012	0.033	0.17	1	-0.21	14	15
HDAC4/HDAC3/SMRT (N-CoR2)	0.006	0.023	-10000	0	-0.18	9	9
HDAC4/SRF	0.01	0.023	0.16	9	-0.18	3	12
HDAC4/ER alpha	-0.034	0.069	-10000	0	-0.21	75	75
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0	0.026	0.18	1	-0.18	4	5
cell motility	0.01	0.015	0.16	6	-10000	0	6
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	-0.006	0	-10000	0	-10000	0	0
HDAC7/HDAC3	-0.003	0	-10000	0	-10000	0	0
BCL6	-0.013	0.047	-10000	0	-0.31	14	14
HDAC4/CaMK II delta B	-0.006	0	-10000	0	-10000	0	0
Hsp90/HDAC6	-0.006	0.019	0.17	5	-0.21	1	6
ESR1	-0.046	0.1	-10000	0	-0.31	75	75
HDAC6/HDAC11	-0.005	0.017	0.17	5	-10000	0	5
Ran/GTP/Exportin 1	0.007	0.039	0.14	46	-10000	0	46
NPC	0.003	0.008	0.13	2	-10000	0	2
MEF2C	-0.017	0.057	-10000	0	-0.31	21	21
RAN	-0.006	0	-10000	0	-10000	0	0
HDAC4/MEF2C	0.004	0.037	-10000	0	-0.15	30	30
GNG2	-0.005	0.01	0.24	1	-10000	0	1
NCOR2	-0.011	0.038	-10000	0	-0.31	9	9
TUBB2A	-0.005	0.01	0.24	1	-10000	0	1
HDAC11	-0.006	0	-10000	0	-10000	0	0
HSP90AA1	-0.006	0.013	-10000	0	-0.31	1	1
RANBP2	-0.005	0.015	0.24	2	-10000	0	2
ANKRA2	-0.006	0.016	0.24	1	-0.31	1	2
RFXANK	-0.005	0.015	0.24	2	-10000	0	2
nuclear import	0.007	0.022	0.21	6	-10000	0	6

×

JNK signaling in the CD4+ TCR 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
LAT/GRAP2/SLP76/HPK1	0.006	0.03	0.15	1	-0.16	17	18
MAP4K1	-0.005	0.015	0.24	2	-10000	0	2
MAP3K8	-0.006	0	-10000	0	-10000	0	0
PRKCB	0	0	-10000	0	-10000	0	0
DBNL	-0.006	0	-10000	0	-10000	0	0
CRKL	-0.006	0	-10000	0	-10000	0	0
MAP3K1	-0.011	0.032	-10000	0	-0.18	17	17
JUN	0.001	0.027	-10000	0	-10000	0	0
MAP3K7	-0.009	0.033	-10000	0	-0.18	17	17
GRAP2	-0.006	0	-10000	0	-10000	0	0
CRK	-0.005	0.01	0.24	1	-10000	0	1
MAP2K4	-0.011	0.034	-10000	0	-0.18	17	17
LAT	-0.006	0	-10000	0	-10000	0	0
LCP2	-0.015	0.053	-10000	0	-0.31	18	18
MAPK8	0	0.017	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.008	0.031	-10000	0	-0.18	17	17
LAT/GRAP2/SLP76/HPK1/HIP-55	0.008	0.029	-10000	0	-0.15	17	17

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.011	0.06	0.24	36	-10000	0	36
HDAC2	-0.001	0.037	0.24	11	-0.31	1	12
GNB1/GNG2	0.007	0.012	0.16	1	-0.19	1	2
forebrain development	-0.007	0.077	-10000	0	-0.43	7	7
GNAO1	-0.004	0.028	0.24	6	-0.31	1	7
SMO/beta Arrestin2	-0.008	0.004	-10000	0	-10000	0	0
SMO	-0.007	0.003	-10000	0	-10000	0	0
ARRB2	-0.006	0.002	-10000	0	-10000	0	0
GLI3/SPOP	-0.004	0.046	-10000	0	-0.36	1	1
mol:GTP	-0.001	0.002	-10000	0	-10000	0	0
GSK3B	-0.006	0	-10000	0	-10000	0	0
GNAI2	-0.006	0.002	-10000	0	-10000	0	0
SIN3/HDAC complex	0.012	0.01	-10000	0	-0.16	1	1
GNAI1	-0.006	0.041	0.24	8	-0.31	5	13
XPO1	0.013	0.067	0.24	46	-10000	0	46
GLI1/Su(fu)	-0.013	0.068	-10000	0	-0.41	7	7
SAP30	-0.005	0.003	-10000	0	-10000	0	0
mol:GDP	-0.007	0.003	-10000	0	-10000	0	0
MIM/GLI2A	-0.01	0.035	0.24	6	-10000	0	6
IFT88	-0.015	0.053	-10000	0	-0.31	18	18
GNAI3	0.035	0.093	0.24	96	-10000	0	96
GLI2	-0.002	0.005	-10000	0	-10000	0	0
GLI3	-0.007	0.047	-10000	0	-0.37	1	1
CSNK1D	-0.006	0	-10000	0	-10000	0	0
CSNK1E	-0.006	0	-10000	0	-10000	0	0
SAP18	-0.005	0.013	-10000	0	-0.31	1	1
embryonic digit morphogenesis	-0.015	0.053	-10000	0	-0.31	18	18
GNG2	-0.005	0.01	0.24	1	-10000	0	1
Gi family/GTP	0.009	0.043	0.18	1	-10000	0	1
SIN3B	-0.004	0.011	0.24	1	-10000	0	1
SIN3A	-0.005	0.003	-10000	0	-10000	0	0
GLI3/Su(fu)	-0.009	0.042	-10000	0	-0.33	1	1
GLI2/Su(fu)	-0.005	0.009	0.19	1	-10000	0	1
FOXA2	-0.056	0.22	-10000	0	-0.9	36	36
neural tube patterning	-0.007	0.077	-10000	0	-0.43	7	7
SPOP	-0.006	0	-10000	0	-10000	0	0
Su(fu)/PIAS1	-0.006	0.01	0.16	1	-10000	0	1
GNB1	-0.006	0.013	-10000	0	-0.31	1	1
CSNK1G2	-0.006	0	-10000	0	-10000	0	0
CSNK1G3	-0.006	0	-10000	0	-10000	0	0
MTSS1	-0.01	0.035	0.24	6	-10000	0	6
embryonic limb morphogenesis	-0.007	0.077	-10000	0	-0.43	7	7
SUFU	-0.005	0.008	0.16	1	-10000	0	1
LGALS3	-0.032	0.086	-10000	0	-0.31	50	50
catabolic process	-0.007	0.037	-10000	0	-0.28	1	1
GLI3A/CBP	-0.015	0.042	-10000	0	-0.31	11	11
KIF3A	-0.005	0.015	0.24	2	-10000	0	2
GLI1	-0.007	0.078	-10000	0	-0.44	7	7
RAB23	-0.006	0	-10000	0	-10000	0	0
CSNK1A1	-0.005	0.015	0.24	2	-10000	0	2
IFT172	-0.007	0.018	-10000	0	-0.31	2	2
RBBP7	-0.006	0.018	-10000	0	-0.31	2	2
Su(fu)/Galectin3	-0.02	0.043	-10000	0	-0.18	1	1
GNAZ	-0.009	0.025	-10000	0	-0.31	4	4
RBBP4	0.003	0.043	0.24	18	-10000	0	18
CSNK1G1	-0.006	0	-10000	0	-10000	0	0
PIAS1	-0.005	0.01	0.24	1	-10000	0	1
PRKACA	-0.006	0	-10000	0	-10000	0	0
GLI2/SPOP	-0.004	0.005	-10000	0	-10000	0	0
STK36	-0.007	0.011	0.24	1	-10000	0	1
Gi family/GNB1/GNG2/GDP	0.011	0.043	0.27	1	-10000	0	1
PTCH1	-0.015	0.13	-10000	0	-0.99	8	8
MIM/GLI1	-0.02	0.11	-10000	0	-0.4	37	37
CREBBP	-0.015	0.042	-10000	0	-0.31	11	11
Su(fu)/SIN3/HDAC complex	0.009	0.038	0.18	12	-10000	0	12

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	-0.007	0.009	0.2	1	-10000	0	1
BAD/BCL-XL/YWHAZ	-0.009	0.006	0.13	1	-10000	0	1
CDKN1B	0.018	0.05	0.25	1	-10000	0	1
CDKN1A	0.014	0.052	-10000	0	-10000	0	0
FRAP1	-0.006	0	-10000	0	-10000	0	0
PRKDC	0.036	0.093	0.24	97	-10000	0	97
FOXO3	0.016	0.051	-10000	0	-10000	0	0
AKT1	0.021	0.051	0.17	2	-10000	0	2
BAD	-0.006	0	-10000	0	-10000	0	0
AKT3	-0.14	0.12	0.16	4	-0.24	323	327
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.018	0.048	-10000	0	-10000	0	0
AKT1/ASK1	0.016	0.046	-10000	0	-10000	0	0
BAD/YWHAZ	0.009	0	-10000	0	-10000	0	0
RICTOR	-0.003	0.025	0.24	6	-10000	0	6
RAF1	-0.006	0	-10000	0	-10000	0	0
JNK cascade	0.003	0.012	-10000	0	-10000	0	0
TSC1	0.017	0.048	-10000	0	-10000	0	0
YWHAZ	-0.006	0	-10000	0	-10000	0	0
AKT1/RAF1	0.018	0.048	-10000	0	-10000	0	0
EP300	-0.007	0.018	-10000	0	-0.31	2	2
mol:GDP	0.021	0.051	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.018	0.048	-10000	0	-10000	0	0
YWHAQ	-0.006	0	-10000	0	-10000	0	0
TBC1D4	-0.003	0.014	0.16	1	-10000	0	1
MAP3K5	-0.006	0.023	0.24	2	-0.31	2	4
MAPKAP1	-0.006	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.01	0.029	-10000	0	-10000	0	0
YWHAH	-0.007	0.022	-10000	0	-0.31	3	3
AKT1S1	0.018	0.048	-10000	0	-10000	0	0
CASP9	0.018	0.048	-10000	0	-10000	0	0
YWHAB	-0.005	0.01	0.24	1	-10000	0	1
p27Kip1/KPNA1	0.016	0.049	0.23	1	-10000	0	1
GBL	-0.006	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.008	0.008	-10000	0	-0.18	1	1
YWHAE	-0.006	0.013	-10000	0	-0.31	1	1
SRC	-0.006	0	-10000	0	-10000	0	0
AKT2/p21CIP1	0.012	0.05	0.19	3	-10000	0	3
KIAA1303	-0.006	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.016	0.029	-10000	0	-10000	0	0
CHUK	0.022	0.055	0.25	8	-10000	0	8
BAD/BCL-XL	0.014	0.047	-10000	0	-10000	0	0
mTORC2	0.013	0.014	0.15	6	-10000	0	6
AKT2	0	0.015	0.16	5	-10000	0	5
FOXO1-3a-4/14-3-3 family	0.014	0.042	-10000	0	-10000	0	0
PDPK1	-0.006	0	-10000	0	-10000	0	0
MDM2	0.018	0.049	-10000	0	-10000	0	0
MAPKKK cascade	-0.017	0.047	-10000	0	-10000	0	0
MDM2/Cbp/p300	0.01	0.052	-10000	0	-10000	0	0
TSC1/TSC2	0.015	0.047	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.01	0.049	-10000	0	-10000	0	0
glucose import	-0.005	0.012	0.14	1	-10000	0	1
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.019	0.038	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.005	0.012	0.14	1	-10000	0	1
GSK3A	0.017	0.048	-10000	0	-10000	0	0
FOXO1	0.016	0.05	-10000	0	-10000	0	0
GSK3B	0.018	0.048	-10000	0	-10000	0	0
SFN	0.003	0.047	0.24	21	-10000	0	21
G1/S transition of mitotic cell cycle	0.015	0.046	-10000	0	-10000	0	0
p27Kip1/14-3-3 family	0.006	0.024	-10000	0	-10000	0	0
PRKACA	-0.006	0	-10000	0	-10000	0	0
KPNA1	-0.005	0.015	0.24	2	-10000	0	2
HSP90AA1	-0.006	0.013	-10000	0	-0.31	1	1
YWHAG	-0.006	0	-10000	0	-10000	0	0
RHEB	0.006	0.052	0.24	26	-10000	0	26
CREBBP	-0.012	0.042	-10000	0	-0.31	11	11

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
GNAO1	-0.004	0.028	0.24	6	-0.31	1	7
CDC42/GTP	0.009	0.037	-10000	0	-0.15	6	6
PLCG1	0.012	0.042	0.15	7	-0.16	6	13
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	-0.006	0	-10000	0	-10000	0	0
GNAI3	0.036	0.093	0.24	96	-10000	0	96
G12/G13	-0.007	0.009	-10000	0	-0.21	1	1
cell migration	0.009	0.037	-10000	0	-0.15	6	6
S1PR5	0	0	-10000	0	-10000	0	0
S1PR4	0	0	-10000	0	-10000	0	0
MAPK3	0.008	0.043	0.17	2	-0.16	6	8
MAPK1	0.011	0.041	0.16	3	-0.16	6	9
S1P/S1P5/Gi	0.014	0.043	0.18	2	-0.17	6	8
GNAI1	-0.005	0.041	0.24	8	-0.31	5	13
CDC42/GDP	-0.003	0	-10000	0	-10000	0	0
S1P/S1P5/G12	0.003	0	-10000	0	-10000	0	0
RHOA	-0.007	0.006	-10000	0	-0.15	1	1
S1P/S1P4/Gi	0.014	0.043	0.18	2	-0.17	6	8
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	-0.008	0.025	-10000	0	-0.31	4	4
S1P/S1P4/G12/G13	0.005	0.007	-10000	0	-0.16	1	1
GNA12	-0.006	0	-10000	0	-10000	0	0
GNA13	-0.006	0.013	-10000	0	-0.31	1	1
CDC42	-0.006	0	-10000	0	-10000	0	0

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	-0.003	0.012	0.14	2	-0.14	2	4
TRAF2/ASK1	0.006	0.014	0.15	2	-0.18	2	4
ATM	0.002	0.043	0.24	18	-10000	0	18
MAP2K3	0	0.036	0.19	1	-0.31	4	5
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.011	0.042	0.2	3	-0.21	5	8
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	-0.01	0.036	-10000	0	-0.31	8	8
TXN	-0.009	0.044	-10000	0	-0.24	20	20
CALM1	-0.012	0.042	-10000	0	-0.31	11	11
GADD45A	0.015	0.069	0.24	48	-10000	0	48
GADD45B	-0.004	0.021	0.24	4	-10000	0	4
MAP3K1	-0.008	0.025	-10000	0	-0.31	4	4
MAP3K6	-0.006	0	-10000	0	-10000	0	0
MAP3K7	-0.003	0.025	0.24	6	-10000	0	6
MAP3K4	-0.006	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	-0.007	0.016	0.17	2	-0.21	2	4
TAK1/TAB family	0.004	0.015	-10000	0	-10000	0	0
RAC1/OSM/MEKK3	0.008	0.007	-10000	0	-0.16	1	1
TRAF2	-0.006	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.009	0.024	-10000	0	-0.25	4	4
TRAF6	0	0.015	0.16	5	-10000	0	5
RAC1	-0.006	0.013	-10000	0	-0.31	1	1
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.006	0	-10000	0	-10000	0	0
CCM2	-0.006	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	0.002	0.025	-10000	0	-0.18	11	11
MAPK11	-0.006	0	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.005	0.026	0.15	2	-0.16	13	15
OSM/MEKK3	-0.007	0	-10000	0	-10000	0	0
TAOK1	0.003	0.03	0.16	19	-0.24	1	20
TAOK2	0.003	0.028	0.16	18	-10000	0	18
TAOK3	0.003	0.028	0.16	18	-10000	0	18
MAP3K7IP1	-0.006	0	-10000	0	-10000	0	0
MAPK14	-0.005	0.01	0.24	1	-10000	0	1
MAP3K7IP2	-0.004	0.018	0.24	3	-10000	0	3
MAP3K5	-0.006	0.023	0.24	2	-0.31	2	4
MAP3K10	-0.006	0	-10000	0	-10000	0	0
MAP3K3	-0.006	0	-10000	0	-10000	0	0
TRX/ASK1	-0.01	0.04	0.17	2	-0.2	22	24
GADD45/MTK1/MTK1	0.02	0.043	0.15	49	-0.15	7	56

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	0.003	0.025	-10000	0	-0.24	6	6
PI3K Class IB/PDE3B	-0.003	0.025	0.24	6	-10000	0	6
PDE3B	-0.003	0.025	0.24	6	-10000	0	6

×

Sumoylation by RanBP2 regulates transcriptional repression

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
HDAC1	0.01	0.06	0.24	36	-10000	0	36
Ran/GTP/Exportin 1/HDAC4	-0.008	0.002	-10000	0	-10000	0	0
MDM2/SUMO1	0.005	0.012	0.15	2	-0.14	2	4
HDAC4	-0.006	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	-0.008	0.003	-10000	0	-10000	0	0
SUMO1	-0.006	0	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1	-0.001	0.006	0.094	2	-10000	0	2
mol:GTP	0	0	-10000	0	-10000	0	0
XPO1	0.007	0.035	0.12	46	-10000	0	46
EntrezGene:23636	0	0	-10000	0	-10000	0	0
RAN	-0.006	0	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	-0.005	0.015	0.24	2	-10000	0	2
SUMO1/HDAC4	0.005	0	-10000	0	-10000	0	0
SUMO1/HDAC1	0.014	0.036	0.15	36	-10000	0	36
RANGAP1	-0.006	0	-10000	0	-10000	0	0
MDM2/SUMO1/SUMO1	0.012	0.019	0.15	7	-0.16	2	9
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	-0.001	0.006	-10000	0	-10000	0	0
Ran/GTP	-0.003	0.005	-10000	0	-10000	0	0
EntrezGene:23225	0	0	-10000	0	-10000	0	0
MDM2	-0.006	0.023	0.24	2	-0.31	2	4
UBE2I	-0.006	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.004	0.032	-10000	0	-10000	0	0
NPC	0.003	0.008	0.13	2	-10000	0	2
PIAS2	-0.004	0.021	0.24	4	-10000	0	4
PIAS1	-0.005	0.01	0.24	1	-10000	0	1
EntrezGene:9972	0	0	-10000	0	-10000	0	0

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.006	0	-10000	0	-10000	0	0
CLTC	0.006	0.032	-10000	0	-0.48	1	1
calcium ion-dependent exocytosis	0.003	0.02	-10000	0	-0.17	1	1
Dynamin 2/GTP	0	0.031	0.13	30	-0.16	1	31
EXOC4	-0.004	0.021	0.24	4	-10000	0	4
CD59	0.004	0.026	-10000	0	-0.43	1	1
CPE	-0.008	0.052	0.17	22	-0.18	31	53
CTNNB1	-0.005	0.015	0.24	2	-10000	0	2
membrane fusion	0.003	0.02	-10000	0	-0.15	1	1
CTNND1	-0.002	0.029	0.12	30	-0.15	1	31
DNM2	-0.005	0.01	0.24	1	-10000	0	1
mol:PI-4-5-P2	0.002	0.021	-10000	0	-0.32	1	1
TSHR	-0.001	0.029	0.17	16	-0.17	1	17
INS	0.003	0.007	-10000	0	-10000	0	0
BIN1	-0.007	0.018	-10000	0	-0.31	2	2
mol:Choline	0.003	0.02	-10000	0	-0.15	1	1
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.003	0.038	0.17	29	-0.17	1	30
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	-0.006	0.013	-10000	0	-0.31	1	1
mol:Ca2+	0	0.031	0.13	30	-0.16	1	31
JUP	0	0.034	-10000	0	-0.43	1	1
ASAP2/amphiphysin II	0.005	0.012	-10000	0	-0.16	3	3
ARF6/GTP	-0.004	0.009	-10000	0	-0.21	1	1
CDH1	0.001	0.033	-10000	0	-0.43	1	1
clathrin-independent pinocytosis	-0.004	0.009	-10000	0	-0.21	1	1
MAPK8IP3	-0.006	0	-10000	0	-10000	0	0
positive regulation of endocytosis	-0.004	0.009	-10000	0	-0.21	1	1
EXOC2	-0.001	0.034	0.24	11	-10000	0	11
substrate adhesion-dependent cell spreading	0.006	0.03	0.2	1	-10000	0	1
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	-0.005	0.01	0.24	1	-10000	0	1
regulation of calcium-dependent cell-cell adhesion	0.007	0.024	0.4	1	-10000	0	1
positive regulation of phagocytosis	-0.006	0.007	-10000	0	-0.17	1	1
ARF6/GTP/JIP3	0.006	0.008	-10000	0	-0.18	1	1
ACAP1	0.003	0.017	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.004	0.026	-10000	0	-0.43	1	1
clathrin heavy chain/ACAP1	0.005	0.029	-10000	0	-0.4	1	1
JIP4/KLC1	0.009	0.011	0.15	2	-0.16	1	3
EXOC1	-0.002	0.031	0.24	9	-10000	0	9
exocyst	0.006	0.03	0.2	1	-10000	0	1
RALA/GTP	-0.003	0.01	0.17	2	-10000	0	2
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.006	0.01	0.15	1	-0.18	1	2
receptor recycling	-0.004	0.009	-10000	0	-0.21	1	1
CTNNA1	-0.003	0.031	0.12	1	-0.15	3	4
NME1	0.003	0.039	0.17	29	-0.17	1	30
clathrin coat assembly	0.006	0.032	0.18	1	-0.48	1	2
IL2RA	0.005	0.028	-10000	0	-0.43	1	1
VAMP3	-0.006	0.007	-10000	0	-0.17	1	1
GLUT4/clathrin heavy chain/ACAP1	-0.004	0.016	-10000	0	-0.38	1	1
EXOC6	0.003	0.046	0.24	20	-10000	0	20
PLD1	0.006	0.028	-10000	0	-10000	0	0
PLD2	-0.001	0.007	-10000	0	-10000	0	0
EXOC5	-0.005	0.015	0.24	2	-10000	0	2
PIP5K1C	0.002	0.021	-10000	0	-0.33	1	1
SDC1	0.004	0.028	-10000	0	-0.43	1	1
ARF6/GDP	0.002	0.033	0.14	29	-0.18	1	30
EXOC7	-0.006	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.002	0.036	-10000	0	-0.42	1	1
mol:Phosphatidic acid	0.003	0.02	-10000	0	-0.15	1	1
endocytosis	-0.005	0.012	0.16	3	-10000	0	3
SCAMP2	-0.006	0	-10000	0	-10000	0	0
ADRB2	0.004	0.031	-10000	0	-0.46	1	1
EXOC3	-0.005	0.01	0.24	1	-10000	0	1
ASAP2	0	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0	0.034	0.14	30	-0.16	1	31
KLC1	-0.005	0.01	0.24	1	-10000	0	1
AVPR2	0.004	0.031	-10000	0	-0.46	1	1
RALA	-0.005	0.015	0.24	2	-10000	0	2
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.006	0.035	-10000	0	-0.4	1	1

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.001	0.031	0.17	18	-10000	0	18
FBXW11	-0.006	0	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	-0.006	0	-10000	0	-10000	0	0
CHUK	0.002	0.043	0.24	18	-10000	0	18
NF kappa B2 p100/RelB	0.016	0.025	-10000	0	-0.15	2	2
NFKB1	-0.01	0.033	-10000	0	-0.31	7	7
MAP3K14	-0.006	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelB	-0.01	0.026	-10000	0	-0.21	9	9
RELB	-0.007	0.018	-10000	0	-0.31	2	2
NFKB2	-0.006	0	-10000	0	-10000	0	0
NF kappa B2 p52/RelB	0.005	0.011	-10000	0	-0.18	2	2
regulation of B cell activation	0.005	0.011	-10000	0	-0.17	2	2

×

Visual signal transduction: Rods

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
mol:K +	-0.006	0	-10000	0	-10000	0	0
GNAT1/GTP	-0.003	0	-10000	0	-10000	0	0
Metarhodopsin II/Arrestin	0.006	0	-10000	0	-10000	0	0
PDE6G/GNAT1/GTP	0.006	0.006	0.15	1	-10000	0	1
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	-0.006	0	-10000	0	-10000	0	0
GRK1	0	0	-10000	0	-10000	0	0
CNG Channel	-0.014	0.016	-10000	0	-0.14	9	9
mol:Na +	-0.016	0.016	-10000	0	-0.14	9	9
mol:ADP	0	0	-10000	0	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.007	0.019	-10000	0	-0.18	6	6
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	-0.016	0.018	-10000	0	-10000	0	0
CNGB1	-0.006	0	-10000	0	-10000	0	0
RDH5	0.002	0.043	0.24	18	-10000	0	18
SAG	-0.006	0	-10000	0	-10000	0	0
mol:Ca2+	-0.017	0.017	-10000	0	-10000	0	0
Na + (4 Units)	-0.017	0.015	-10000	0	-10000	0	0
RGS9	-0.006	0	-10000	0	-10000	0	0
GNB1/GNGT1	-0.005	0.021	0.17	7	-0.21	1	8
GNAT1/GDP	0.008	0.016	-10000	0	-0.15	6	6
GUCY2D	-0.006	0	-10000	0	-10000	0	0
GNGT1	-0.003	0.027	0.24	7	-10000	0	7
GUCY2F	-0.006	0	-10000	0	-10000	0	0
GNB5	-0.009	0.031	-10000	0	-0.31	6	6
mol:GMP (4 units)	-0.008	0.01	0.13	3	-10000	0	3
mol:11-cis-retinal	0.002	0.043	0.24	18	-10000	0	18
mol:cGMP	-0.011	0.009	0.15	2	-10000	0	2
GNB1	-0.006	0.013	-10000	0	-0.31	1	1
Rhodopsin	-0.001	0.031	0.17	18	-10000	0	18
SLC24A1	-0.006	0	-10000	0	-10000	0	0
CNGA1	-0.011	0.038	-10000	0	-0.31	9	9
Metarhodopsin II	0.003	0	-10000	0	-10000	0	0
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.012	0.008	0.15	2	-10000	0	2
RGS9BP	-0.006	0	-10000	0	-10000	0	0
Metarhodopsin II/Transducin	-0.001	0.014	-10000	0	-0.18	1	1
GCAP Family/Ca ++	0.009	0.008	0.15	2	-10000	0	2
PDE6A/B	-0.006	0.01	0.17	2	-10000	0	2
mol:Pi	0.007	0.019	-10000	0	-0.18	6	6
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	0.01	0.017	0.15	7	-0.16	1	8
PDE6B	-0.005	0.01	0.24	1	-10000	0	1
PDE6A	-0.005	0.01	0.24	1	-10000	0	1
PDE6G	-0.005	0.01	0.24	1	-10000	0	1
RHO	-0.006	0	-10000	0	-10000	0	0
PDE6	-0.013	0.017	-10000	0	-10000	0	0
GUCA1A	-0.006	0	-10000	0	-10000	0	0
GC2/GCAP Family	0.012	0.008	0.15	2	-10000	0	2
GUCA1C	-0.005	0.015	0.24	2	-10000	0	2
GUCA1B	-0.006	0	-10000	0	-10000	0	0

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	0.008	0	-9999	-10000	0	0
RGS9BP	-0.006	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0	0	-9999	-10000	0	0
mol:Na +	0.006	0	-9999	-10000	0	0
mol:ADP	-0.003	0	-9999	-10000	0	0
GNAT2	-0.006	0	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.007	0.019	-9999	-0.18	6	6
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0.006	0	-9999	-10000	0	0
GRK7	-0.006	0	-9999	-10000	0	0
CNGB3	-0.006	0	-9999	-10000	0	0
Cone Metarhodopsin II/X-Arrestin	-0.003	0	-9999	-10000	0	0
mol:Ca2+	-0.007	0	-9999	-10000	0	0
Cone PDE6	0.011	0.017	-9999	-0.15	6	6
Cone Metarhodopsin II	0.003	0	-9999	-10000	0	0
Na + (4 Units)	0.008	0	-9999	-10000	0	0
GNAT2/GDP	0.008	0.016	-9999	-0.15	6	6
GNB5	-0.009	0.031	-9999	-0.31	6	6
mol:GMP (4 units)	-0.007	0	-9999	-10000	0	0
Cone Transducin	0.008	0	-9999	-10000	0	0
SLC24A2	-0.006	0	-9999	-10000	0	0
GNB3/GNGT2	-0.007	0	-9999	-10000	0	0
GNB3	-0.006	0	-9999	-10000	0	0
GNAT2/GTP	-0.003	0	-9999	-10000	0	0
CNGA3	-0.006	0	-9999	-10000	0	0
ARR3	-0.006	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	0.006	0	-9999	-10000	0	0
mol:Pi	0.007	0.019	-9999	-0.18	6	6
Cone CNG Channel	-0.011	0	-9999	-10000	0	0
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.006	0	-9999	-10000	0	0
RGS9	-0.006	0	-9999	-10000	0	0
PDE6C	-0.006	0	-9999	-10000	0	0
GNGT2	-0.006	0	-9999	-10000	0	0
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	-0.006	0	-9999	-10000	0	0

×

Glypican 2 network

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.Total.Perturbations
MDK	-0.005	0.01	0.24	1	-9999	1
GPC2	-0.006	0	-10000	0	-9999	0
GPC2/Midkine	-0.007	0.007	0.17	1	-9999	1
neuron projection morphogenesis	-0.007	0.007	0.17	1	-9999	1

×

Rapid glucocorticoid signaling

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0.008	0.009	0.14	1	-0.15	1	2
MAPK9	-0.001	0.012	0.16	1	-0.24	1	2
adrenocorticotropin secretion	-0.003	0.008	0.2	1	-10000	0	1
GNB1/GNG2	0.006	0.01	0.15	1	-0.18	1	2
GNB1	-0.006	0.013	-10000	0	-0.31	1	1
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	-0.001	0.007	0.16	1	-10000	0	1
Gs family/GTP	0.003	0	-10000	0	-10000	0	0
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	0.001	0	-10000	0	-10000	0	0
GNAL	-0.006	0	-10000	0	-10000	0	0
GNG2	-0.005	0.01	0.24	1	-10000	0	1
CRH	-0.005	0.01	0.24	1	-10000	0	1
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.001	0.016	0.16	6	-10000	0	6
MAPK11	-0.001	0	-10000	0	-10000	0	0

pid_entity	TCGA.61.2614	TCGA.61.2613	TCGA.61.2612	TCGA.61.2113
109_MAP3K5	-0.0032	-0.0032	-0.0032	-0.0032
47_PPARGC1A	-0.0058	-0.0058	-0.0058	-0.0058
105_BMP4	-0.0058	-0.0058	-0.0058	-0.0058
105_BMP6	-0.0058	-0.0058	-0.0058	-0.0058
105_BMP7	0.24	-0.0058	-0.0058	-0.0058
105_BMP2	-0.0058	-0.0058	-0.0058	-0.0058
131_RELN/VLDLR	0.011	0.011	0.011	0.011
30_TGFB1/TGF beta receptor Type II	-0.0058	-0.0058	-0.0058	-0.0058
84_STAT5B	-0.041	-0.041	-0.041	0.065
84_STAT5A	-0.041	-0.041	-0.041	0.065