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

Pathway.Name	Avg.Num.Perturbations
Aurora B signaling	140
FOXM1 transcription factor network	133
HIF-1-alpha transcription factor network	120
Signaling events regulated by Ret tyrosine kinase	111
Angiopoietin receptor Tie2-mediated signaling	107
Endothelins	103
p75(NTR)-mediated signaling	97
PDGFR-alpha signaling pathway	90
Integrins in angiogenesis	85
Nongenotropic Androgen signaling	68

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
Aurora B signaling	0.2729	140	9400	67	-0.49	0.025	1000	-1000	-0.032	-1000
FOXM1 transcription factor network	0.2593	133	6823	51	-0.9	0.011	1000	-1000	-0.12	-1000
HIF-1-alpha transcription factor network	0.2339	120	9193	76	-0.45	0.017	1000	-1000	-0.048	-1000
Signaling events regulated by Ret tyrosine kinase	0.2164	111	9171	82	-0.19	0.011	1000	-1000	-0.044	-1000
Angiopoietin receptor Tie2-mediated signaling	0.2086	107	9454	88	-0.33	0.043	1000	-1000	-0.064	-1000
Endothelins	0.2008	103	9917	96	-0.38	0.016	1000	-1000	-0.043	-1000
p75(NTR)-mediated signaling	0.1891	97	12159	125	-0.2	0.03	1000	-1000	-0.046	-1000
PDGFR-alpha signaling pathway	0.1754	90	3991	44	-0.32	0.025	1000	-1000	-0.039	-1000
Integrins in angiogenesis	0.1657	85	7141	84	-0.32	0.023	1000	-1000	-0.047	-1000
Nongenotropic Androgen signaling	0.1326	68	3575	52	-0.24	0.12	1000	-1000	-0.026	-1000
Cellular roles of Anthrax toxin	0.1306	67	2628	39	-0.13	0.02	1000	-1000	-0.016	-1000
S1P3 pathway	0.1306	67	2845	42	-0.46	0.016	1000	-1000	-0.02	-1000
Aurora C signaling	0.1248	64	451	7	-0.24	0.01	1000	-1000	-0.016	-1000
Signaling events mediated by the Hedgehog family	0.1228	63	3287	52	-0.26	0.14	1000	-1000	-0.023	-1000
Reelin signaling pathway	0.1209	62	3501	56	-0.18	0.029	1000	-1000	-0.038	-1000
LPA4-mediated signaling events	0.1150	59	714	12	-0.13	0.015	1000	-1000	-0.01	-1000
Signaling mediated by p38-alpha and p38-beta	0.1150	59	2603	44	-0.1	0.011	1000	-1000	-0.031	-1000
Glypican 1 network	0.1072	55	2685	48	-0.24	0.021	1000	-1000	-0.018	-1000
Effects of Botulinum toxin	0.1072	55	1449	26	-0.12	0.017	1000	-1000	-0.028	-1000
Fc-epsilon receptor I signaling in mast cells	0.1033	53	5212	97	-0.15	0.029	1000	-1000	-0.044	-1000
IGF1 pathway	0.1033	53	3033	57	-0.082	0.022	1000	-1000	-0.042	-1000
Thromboxane A2 receptor signaling	0.0955	49	5217	105	-0.19	0.029	1000	-1000	-0.032	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0936	48	5815	120	-0.19	0.14	1000	-1000	-0.037	-1000
Aurora A signaling	0.0897	46	2781	60	-0.22	0.024	1000	-1000	-0.011	-1000
Wnt signaling	0.0897	46	322	7	-0.058	-0.002	1000	-1000	-0.013	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0897	46	3151	68	-0.18	0.078	1000	-1000	-0.078	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0897	46	3615	78	-0.11	0.047	1000	-1000	-0.04	-1000
PLK1 signaling events	0.0858	44	3788	85	-0.25	0.055	1000	-1000	-0.024	-1000
Ephrin A reverse signaling	0.0799	41	290	7	-0.031	0	1000	-1000	-0.009	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0780	40	1374	34	-0.044	0.011	1000	-1000	-0.018	-1000
Osteopontin-mediated events	0.0780	40	1551	38	-0.13	0.014	1000	-1000	-0.044	-1000
amb2 Integrin signaling	0.0780	40	3310	82	-0.17	0.022	1000	-1000	-0.037	-1000
FOXA2 and FOXA3 transcription factor networks	0.0760	39	1799	46	-0.22	0.016	1000	-1000	-0.03	-1000
BMP receptor signaling	0.0760	39	3200	81	-0.29	0.036	1000	-1000	-0.051	-1000
TCGA08_retinoblastoma	0.0760	39	314	8	-0.12	0.02	1000	-1000	-0.01	-1000
Plasma membrane estrogen receptor signaling	0.0741	38	3315	86	-0.15	0.065	1000	-1000	-0.047	-1000
Ras signaling in the CD4+ TCR pathway	0.0721	37	642	17	-0.09	0.014	1000	-1000	-0.016	-1000
Syndecan-1-mediated signaling events	0.0663	34	1185	34	-0.11	0.011	1000	-1000	-0.019	-1000
Noncanonical Wnt signaling pathway	0.0663	34	904	26	-0.12	0.011	1000	-1000	-0.018	-1000
Ephrin B reverse signaling	0.0643	33	1594	48	-0.079	0.017	1000	-1000	-0.034	-1000
TCGA08_p53	0.0624	32	227	7	-0.075	0.038	1000	-1000	-0.005	-1000
LPA receptor mediated events	0.0624	32	3350	102	-0.15	0.026	1000	-1000	-0.042	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0604	31	1707	54	-0.15	0.021	1000	-1000	-0.044	-1000
IL4-mediated signaling events	0.0604	31	2906	91	-0.58	0.29	1000	-1000	-0.13	-1000
S1P1 pathway	0.0604	31	1127	36	-0.15	0.011	1000	-1000	-0.035	-1000
Syndecan-4-mediated signaling events	0.0585	30	2065	67	-0.26	0.015	1000	-1000	-0.029	-1000
S1P5 pathway	0.0565	29	501	17	-0.098	0.036	1000	-1000	-0.017	-1000
Arf6 signaling events	0.0546	28	1788	62	-0.1	0.026	1000	-1000	-0.037	-1000
FAS signaling pathway (CD95)	0.0546	28	1356	47	-0.069	0.033	1000	-1000	-0.023	-1000
EGFR-dependent Endothelin signaling events	0.0546	28	604	21	-0.12	0.02	1000	-1000	-0.037	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0526	27	1437	52	-0.082	0.032	1000	-1000	-0.033	-1000
TCGA08_rtk_signaling	0.0507	26	686	26	-0.17	0.021	1000	-1000	-0.012	-1000
IL6-mediated signaling events	0.0487	25	1880	75	-0.13	0.061	1000	-1000	-0.033	-1000
Insulin Pathway	0.0487	25	1897	74	-0.16	0.029	1000	-1000	-0.04	-1000
Coregulation of Androgen receptor activity	0.0468	24	1897	76	-0.12	0.021	1000	-1000	-0.028	-1000
Visual signal transduction: Cones	0.0468	24	918	38	-0.085	0.011	1000	-1000	-0.029	-1000
Glypican 2 network	0.0468	24	96	4	-0.006	0.004	1000	-1000	-0.005	-1000
Calcium signaling in the CD4+ TCR pathway	0.0468	24	752	31	-0.13	0.016	1000	-1000	-0.042	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0448	23	2004	85	-0.23	0.012	1000	-1000	-0.04	-1000
Glucocorticoid receptor regulatory network	0.0448	23	2709	114	-0.21	0.04	1000	-1000	-0.039	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0429	22	2757	125	-0.082	0.028	1000	-1000	-0.051	-1000
IL2 signaling events mediated by STAT5	0.0429	22	487	22	-0.098	0.055	1000	-1000	-0.025	-1000
BCR signaling pathway	0.0429	22	2235	99	-0.065	0.047	1000	-1000	-0.049	-1000
Regulation of Androgen receptor activity	0.0429	22	1541	70	-0.18	0.022	1000	-1000	-0.038	-1000
EPHB forward signaling	0.0409	21	1791	85	-0.033	0.029	1000	-1000	-0.046	-1000
S1P4 pathway	0.0409	21	548	25	-0.098	0.023	1000	-1000	-0.016	-1000
Syndecan-2-mediated signaling events	0.0390	20	1400	69	-0.11	0.027	1000	-1000	-0.011	-1000
Signaling events mediated by PTP1B	0.0390	20	1524	76	-0.12	0.02	1000	-1000	-0.037	-1000
Hedgehog signaling events mediated by Gli proteins	0.0390	20	1347	65	-0.098	0.037	1000	-1000	-0.035	-1000
Nectin adhesion pathway	0.0390	20	1276	63	-0.078	0.021	1000	-1000	-0.039	-1000
Rapid glucocorticoid signaling	0.0390	20	419	20	-0.063	0.011	1000	-1000	-0.009	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0370	19	645	33	-0.16	0.033	1000	-1000	-0.015	-1000
Presenilin action in Notch and Wnt signaling	0.0351	18	1131	61	-0.13	0.03	1000	-1000	-0.035	-1000
Regulation of p38-alpha and p38-beta	0.0351	18	996	54	-0.19	0.044	1000	-1000	-0.031	-1000
Class I PI3K signaling events mediated by Akt	0.0331	17	1161	68	-0.21	0.038	1000	-1000	-0.019	-1000
Visual signal transduction: Rods	0.0331	17	898	52	-0.085	0.016	1000	-1000	-0.044	-1000
Regulation of nuclear SMAD2/3 signaling	0.0312	16	2230	136	-0.13	0.043	1000	-1000	-0.035	-1000
BARD1 signaling events	0.0312	16	918	57	-0.11	0.027	1000	-1000	-0.029	-1000
IL1-mediated signaling events	0.0292	15	947	62	-0.027	0.039	1000	-1000	-0.045	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0292	15	1296	83	-0.21	0.037	1000	-1000	-0.029	-1000
Retinoic acid receptors-mediated signaling	0.0292	15	926	58	-0.039	0.022	1000	-1000	-0.035	-1000
Signaling events mediated by PRL	0.0273	14	508	34	-0.11	0.027	1000	-1000	-0.016	-1000
JNK signaling in the CD4+ TCR pathway	0.0253	13	225	17	-0.016	0.03	1000	-1000	-0.016	-1000
FoxO family signaling	0.0253	13	838	64	-0.21	0.044	1000	-1000	-0.035	-1000
TCR signaling in naïve CD8+ T cells	0.0253	13	1217	93	-0.047	0.043	1000	-1000	-0.036	-1000
Canonical Wnt signaling pathway	0.0253	13	673	51	-0.081	0.045	1000	-1000	-0.035	-1000
Regulation of Telomerase	0.0253	13	1389	102	-0.31	0.037	1000	-1000	-0.059	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0234	12	353	28	-0.098	0.031	1000	-1000	-0.014	-1000
Insulin-mediated glucose transport	0.0234	12	414	32	-0.21	0.024	1000	-1000	-0.021	-1000
mTOR signaling pathway	0.0234	12	653	53	-0.024	0.017	1000	-1000	-0.031	-1000
IFN-gamma pathway	0.0234	12	873	68	-0.22	0.051	1000	-1000	-0.045	-1000
IL2 signaling events mediated by PI3K	0.0234	12	696	58	-0.11	0.041	1000	-1000	-0.05	-1000
PDGFR-beta signaling pathway	0.0234	12	1190	97	-0.024	0.037	1000	-1000	-0.04	-1000
IL12-mediated signaling events	0.0214	11	980	87	-0.34	0.046	1000	-1000	-0.087	-1000
ErbB4 signaling events	0.0214	11	770	69	-0.073	0.03	1000	-1000	-0.046	-1000
Class IB PI3K non-lipid kinase events	0.0214	11	33	3	-0.003	0.003	1000	-1000	-0.007	-1000
ErbB2/ErbB3 signaling events	0.0195	10	708	65	-0.13	0.022	1000	-1000	-0.034	-1000
Signaling events mediated by HDAC Class III	0.0195	10	439	40	-0.081	0.016	1000	-1000	-0.018	-1000
Signaling mediated by p38-gamma and p38-delta	0.0195	10	159	15	-0.014	0.02	1000	-1000	-0.013	-1000
Syndecan-3-mediated signaling events	0.0175	9	344	35	-0.088	0.03	1000	-1000	-0.018	-1000
Signaling events mediated by HDAC Class II	0.0156	8	616	75	-0.068	0.027	1000	-1000	-0.023	-1000
Ceramide signaling pathway	0.0156	8	635	76	-0.074	0.037	1000	-1000	-0.017	-1000
HIF-2-alpha transcription factor network	0.0156	8	380	43	-0.14	0.021	1000	-1000	-0.043	-1000
IL27-mediated signaling events	0.0156	8	453	51	-0.073	0.019	1000	-1000	-0.032	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0156	8	611	74	-0.074	0.059	1000	-1000	-0.043	-1000
EPO signaling pathway	0.0136	7	388	55	-0.022	0.036	1000	-1000	-0.041	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0136	7	293	37	-0.024	0.026	1000	-1000	-0.023	-1000
IL23-mediated signaling events	0.0136	7	458	60	-0.033	0.063	1000	-1000	-0.12	-1000
Caspase cascade in apoptosis	0.0097	5	417	74	-0.018	0.05	1000	-1000	-0.019	-1000
ceramide signaling pathway	0.0097	5	275	49	-0.029	0.039	1000	-1000	-0.019	-1000
Arf6 trafficking events	0.0097	5	370	71	-0.21	0.033	1000	-1000	-0.032	-1000
p38 MAPK signaling pathway	0.0097	5	255	44	-0.045	0.029	1000	-1000	-0.032	-1000
PLK2 and PLK4 events	0.0078	4	12	3	0.008	0.015	1000	-1000	-0.008	-1000
Class I PI3K signaling events	0.0078	4	346	73	-0.014	0.052	1000	-1000	-0.032	-1000
Canonical NF-kappaB pathway	0.0058	3	137	39	-0.018	0.056	1000	-1000	-0.04	-1000
TRAIL signaling pathway	0.0058	3	173	48	-0.001	0.036	1000	-1000	-0.035	-1000
Signaling events mediated by HDAC Class I	0.0058	3	355	104	-0.029	0.042	1000	-1000	-0.023	-1000
Paxillin-dependent events mediated by a4b1	0.0058	3	138	36	-0.03	0.031	1000	-1000	-0.034	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0058	3	173	45	-0.018	0.053	1000	-1000	-0.048	-1000
VEGFR1 specific signals	0.0058	3	218	56	-0.082	0.05	1000	-1000	-0.017	-1000
E-cadherin signaling in keratinocytes	0.0058	3	129	43	-0.032	0.035	1000	-1000	-0.024	-1000
a4b1 and a4b7 Integrin signaling	0.0039	2	11	5	0.008	0.014	1000	-1000	-0.008	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0019	1	37	23	0.002	0.035	1000	-1000	-0.022	-1000
Arf6 downstream pathway	0.0019	1	53	43	-0.022	0.022	1000	-1000	-0.022	-1000
Atypical NF-kappaB pathway	0.0019	1	33	31	0	0.039	1000	-1000	-0.011	-1000
E-cadherin signaling in the nascent adherens junction	0.0019	1	101	76	-0.003	0.046	1000	-1000	-0.044	-1000
E-cadherin signaling events	0.0019	1	9	5	0.008	0.02	1000	-1000	-0.005	-1000
Circadian rhythm pathway	0.0000	0	13	22	-0.011	0.039	1000	-1000	-0.025	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	0	27	0	0.027	1000	-1000	-0.027	-1000
Arf1 pathway	0.0000	0	7	54	0	0.027	1000	-1000	-0.015	-1000
Alternative NF-kappaB pathway	0.0000	0	2	13	0	0.032	1000	-1000	-0.011	-1000
Total	NA	3771	229339	7203	-17	4.4	131000	-131000	-4.3	-131000

Aurora B signaling

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
Condensin I complex	-0.069	0.046	-10000	0	-10000	0	0
STMN1	-0.14	0.063	-10000	0	-0.17	447	447
Aurora B/RasGAP/Survivin	-0.22	0.095	-10000	0	-0.27	402	402
Chromosomal passenger complex/Cul3 protein complex	-0.077	0.082	-10000	0	-0.24	96	96
BIRC5	-0.22	0.11	-10000	0	-0.27	423	423
DES	-0.49	0.22	-10000	0	-0.58	443	443
Aurora C/Aurora B/INCENP	-0.098	0.05	-10000	0	-0.25	2	2
Aurora B/TACC1	-0.16	0.11	-10000	0	-0.19	457	457
Aurora B/PP2A	-0.14	0.064	-10000	0	-0.17	447	447
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	-0.011	0.009	-10000	0	-10000	0	0
mitotic metaphase/anaphase transition	-0.005	0.002	-10000	0	-10000	0	0
NDC80	-0.15	0.076	-10000	0	-0.25	54	54
Cul3 protein complex	-0.026	0.1	-10000	0	-0.24	96	96
KIF2C	-0.027	0.017	-10000	0	-10000	0	0
PEBP1	0.003	0.004	-10000	0	-10000	0	0
KIF20A	-0.25	0.08	-10000	0	-0.28	469	469
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	-0.14	0.07	-10000	0	-0.17	447	447
SEPT1	0.01	0.019	-10000	0	-0.42	1	1
SMC2	0.01	0.012	-10000	0	-0.27	1	1
SMC4	0.011	0	-10000	0	-10000	0	0
NSUN2/NPM1/Nucleolin	0.025	0.012	-10000	0	-10000	0	0
PSMA3	0.011	0	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.004	0.001	-10000	0	-10000	0	0
H3F3B	-0.046	0.024	-10000	0	-10000	0	0
AURKB	-0.23	0.097	-10000	0	-0.27	447	447
AURKC	0.01	0.018	-10000	0	-0.27	2	2
CDCA8	-0.15	0.14	-10000	0	-0.27	286	286
cytokinesis	-0.093	0.043	-10000	0	-10000	0	0
Aurora B/Septin1	-0.069	0.062	-10000	0	-0.29	1	1
AURKA	-0.082	0.13	-10000	0	-0.28	164	164
INCENP	0.006	0.003	-10000	0	-10000	0	0
KLHL13	-0.069	0.17	-10000	0	-0.42	96	96
BUB1	-0.21	0.12	-10000	0	-0.28	393	393
hSgo1/Aurora B/Survivin	-0.3	0.12	-10000	0	-0.35	432	432
EVI5	0.012	0.001	-10000	0	-10000	0	0
RhoA/GTP	-0.055	0.04	-10000	0	-0.18	16	16
SGOL1	-0.2	0.12	-10000	0	-0.27	391	391
CENPA	-0.046	0.028	-10000	0	-10000	0	0
NCAPG	-0.17	0.14	-10000	0	-0.27	325	325
Aurora B/HC8 Proteasome	-0.14	0.064	-10000	0	-0.17	447	447
NCAPD2	0.011	0	-10000	0	-10000	0	0
Aurora B/PP1-gamma	-0.14	0.064	-10000	0	-0.17	447	447
RHOA	0.011	0	-10000	0	-10000	0	0
NCAPH	-0.2	0.12	-10000	0	-0.27	384	384
NPM1	-0.009	0.007	-10000	0	-10000	0	0
RASA1	0.006	0.042	-10000	0	-0.42	5	5
KLHL9	0.01	0.019	-10000	0	-0.42	1	1
mitotic prometaphase	-0.007	0.003	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.14	0.064	-10000	0	-0.17	447	447
PPP1CC	0.011	0	-10000	0	-10000	0	0
Centraspindlin	-0.064	0.045	-10000	0	-0.2	17	17
RhoA/GDP	0.008	0	-10000	0	-10000	0	0
NSUN2	-0.009	0.007	-10000	0	-10000	0	0
MYLK	-0.21	0.15	-10000	0	-0.34	287	287
KIF23	0	0.051	-10000	0	-0.28	17	17
VIM	-0.15	0.072	-10000	0	-0.17	447	447
RACGAP1	0.009	0.018	-10000	0	-0.27	2	2
mitosis	0	0	-10000	0	-10000	0	0
NCL	-0.009	0.007	-10000	0	-10000	0	0
Chromosomal passenger complex	-0.072	0.041	-10000	0	-10000	0	0
Chromosomal passenger complex/EVI5	-0.1	0.23	0.19	166	-0.3	291	457
TACC1	-0.076	0.17	-10000	0	-0.42	104	104
PPP2R5D	0.011	0	-10000	0	-10000	0	0
CUL3	0.011	0	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.53	0.35	-9999	-0.94	161	161
PLK1	-0.1	0.062	-9999	-10000	0	0
BIRC5	-0.12	0.054	-9999	-10000	0	0
HSPA1B	-0.53	0.35	-9999	-0.94	161	161
MAP2K1	-0.019	0.017	-9999	-10000	0	0
BRCA2	-0.53	0.35	-9999	-0.94	164	164
FOXM1	-0.63	0.45	-9999	-1.1	200	200
XRCC1	-0.53	0.35	-9999	-0.94	160	160
FOXM1B/p19	-0.57	0.4	-9999	-0.93	225	225
Cyclin D1/CDK4	-0.49	0.32	-9999	-0.86	159	159
CDC2	-0.56	0.37	-9999	-0.93	201	201
TGFA	-0.48	0.31	-9999	-0.83	162	162
SKP2	-0.53	0.35	-9999	-0.94	162	162
CCNE1	-0.12	0.14	-9999	-0.28	225	225
CKS1B	-0.53	0.35	-9999	-0.92	173	173
RB1	-0.19	0.12	-9999	-0.64	6	6
FOXM1C/SP1	-0.58	0.4	-9999	-1	185	185
AURKB	-0.12	0.05	-9999	-10000	0	0
CENPF	-0.56	0.36	-9999	-0.97	163	163
CDK4	0	0.006	-9999	-10000	0	0
MYC	-0.48	0.31	-9999	-0.84	166	166
CHEK2	-0.019	0.017	-9999	-10000	0	0
ONECUT1	-0.52	0.34	-9999	-0.9	169	169
CDKN2A	-0.11	0.14	-9999	-0.27	224	224
LAMA4	-0.57	0.41	-9999	-1.1	168	168
FOXM1B/HNF6	-0.58	0.4	-9999	-1	169	169
FOS	-0.7	0.51	-9999	-1.2	220	220
SP1	0.011	0.001	-9999	-10000	0	0
CDC25B	-0.53	0.35	-9999	-0.94	161	161
response to radiation	-0.028	0.015	-9999	-10000	0	0
CENPB	-0.53	0.35	-9999	-0.94	160	160
CENPA	-0.57	0.36	-9999	-0.93	199	199
NEK2	-0.57	0.36	-9999	-0.98	165	165
HIST1H2BA	-0.53	0.35	-9999	-0.94	163	163
CCNA2	-0.077	0.13	-9999	-0.28	144	144
EP300	0.011	0	-9999	-10000	0	0
CCNB1/CDK1	-0.6	0.41	-9999	-1	182	182
CCNB2	-0.57	0.36	-9999	-0.94	190	190
CCNB1	-0.56	0.37	-9999	-0.95	191	191
ETV5	-0.53	0.35	-9999	-0.95	160	160
ESR1	-0.58	0.42	-9999	-1.1	173	173
CCND1	-0.5	0.33	-9999	-0.88	159	159
GSK3A	-0.012	0.014	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	-0.11	0.12	-9999	-0.21	270	270
CDK2	0.003	0.004	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.034	0.019	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.56	0.37	-9999	-0.92	211	211
GAS1	-0.9	0.51	-9999	-1.2	346	346
MMP2	-0.54	0.38	-9999	-0.99	161	161
RB1/FOXM1C	-0.52	0.35	-9999	-0.93	164	164
CREBBP	0.01	0.019	-9999	-0.42	1	1

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.33	0.39	-9999	-0.77	168	168
HDAC7	0.012	0.001	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.27	0.35	-9999	-0.72	133	133
SMAD4	0.011	0.019	-9999	-0.42	1	1
ID2	-0.33	0.39	-9999	-0.77	168	168
AP1	-0.088	0.15	-9999	-0.29	174	174
ABCG2	-0.44	0.45	-9999	-0.84	246	246
HIF1A	-0.044	0.062	-9999	-10000	0	0
TFF3	-0.37	0.42	-9999	-0.8	201	201
GATA2	-0.028	0.12	-9999	-0.42	48	48
AKT1	-0.056	0.082	-9999	-0.21	43	43
response to hypoxia	-0.071	0.085	-9999	-0.21	72	72
MCL1	-0.33	0.39	-9999	-0.77	168	168
NDRG1	-0.33	0.39	-9999	-0.77	168	168
SERPINE1	-0.33	0.39	-9999	-0.77	169	169
FECH	-0.33	0.39	-9999	-0.77	168	168
FURIN	-0.33	0.39	-9999	-0.77	168	168
NCOA2	-0.003	0.079	-9999	-0.42	18	18
EP300	-0.065	0.13	-9999	-0.34	62	62
HMOX1	-0.33	0.39	-9999	-0.77	168	168
BHLHE40	-0.33	0.39	-9999	-0.77	168	168
BHLHE41	-0.33	0.4	-9999	-0.79	170	170
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.036	0.086	-9999	-0.3	5	5
ENG	-0.023	0.083	-9999	-0.28	5	5
JUN	0.006	0.046	-9999	-0.42	6	6
RORA	-0.34	0.4	-9999	-0.8	169	169
ABCB1	-0.33	0.48	-9999	-1.2	128	128
TFRC	-0.33	0.39	-9999	-0.77	168	168
CXCR4	-0.33	0.39	-9999	-0.77	168	168
TF	-0.33	0.4	-9999	-0.78	170	170
CITED2	-0.33	0.39	-9999	-0.78	170	170
HIF1A/ARNT	-0.35	0.46	-9999	-0.86	168	168
LDHA	-0.048	0.049	-9999	-10000	0	0
ETS1	-0.33	0.39	-9999	-0.77	168	168
PGK1	-0.33	0.39	-9999	-0.77	168	168
NOS2	-0.33	0.39	-9999	-0.77	169	169
ITGB2	-0.33	0.39	-9999	-0.77	168	168
ALDOA	-0.33	0.39	-9999	-0.77	168	168
Cbp/p300/CITED2	-0.35	0.44	-9999	-0.89	150	150
FOS	-0.13	0.2	-9999	-0.42	174	174
HK2	-0.33	0.39	-9999	-0.77	169	169
SP1	0.007	0.027	-9999	-10000	0	0
GCK	-0.2	0.44	-9999	-1.3	62	62
HK1	-0.33	0.39	-9999	-0.77	168	168
NPM1	-0.33	0.39	-9999	-0.77	168	168
EGLN1	-0.33	0.39	-9999	-0.77	168	168
CREB1	0.017	0	-9999	-10000	0	0
PGM1	-0.33	0.39	-9999	-0.77	168	168
SMAD3	0.008	0.038	-9999	-0.42	4	4
EDN1	-0.14	0.24	-9999	-0.6	76	76
IGFBP1	-0.36	0.41	-9999	-0.8	180	180
VEGFA	-0.22	0.31	-9999	-0.66	108	108
HIF1A/JAB1	-0.019	0.037	-9999	-10000	0	0
CP	-0.35	0.41	-9999	-0.79	188	188
CXCL12	-0.45	0.45	-9999	-0.84	252	252
COPS5	0.011	0.001	-9999	-10000	0	0
SMAD3/SMAD4	0.015	0.03	-9999	-0.28	5	5
BNIP3	-0.33	0.39	-9999	-0.77	168	168
EGLN3	-0.33	0.39	-9999	-0.77	169	169
CA9	-0.38	0.42	-9999	-0.8	205	205
TERT	-0.37	0.41	-9999	-0.8	195	195
ENO1	-0.33	0.39	-9999	-0.77	168	168
PFKL	-0.33	0.39	-9999	-0.77	168	168
NCOA1	0.01	0.019	-9999	-0.42	1	1
ADM	-0.33	0.39	-9999	-0.77	176	176
ARNT	-0.044	0.061	-9999	-10000	0	0
HNF4A	-0.029	0.092	-9999	-0.28	56	56
ADFP	-0.34	0.38	-9999	-0.76	178	178
SLC2A1	-0.22	0.31	-9999	-0.65	113	113
LEP	-0.33	0.39	-9999	-0.77	168	168
HIF1A/ARNT/Cbp/p300	-0.28	0.36	-9999	-0.73	145	145
EPO	-0.18	0.26	-9999	-0.7	31	31
CREBBP	-0.066	0.13	-9999	-0.34	62	62
HIF1A/ARNT/Cbp/p300/HDAC7	-0.26	0.35	-9999	-0.73	124	124
PFKFB3	-0.33	0.39	-9999	-0.77	168	168
NT5E	-0.36	0.42	-9999	-0.82	179	179

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.032	0.034	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.12	0.13	-9999	-0.34	89	89
JUN	-0.077	0.13	-9999	-0.39	33	33
HRAS	0.011	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.1	0.13	-9999	-0.23	244	244
RAP1A	0.011	0	-9999	-10000	0	0
FRS2	0.011	0	-9999	-10000	0	0
RAP1A/GDP	0.008	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.1	0.13	-9999	-0.23	243	243
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.011	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.011	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.09	0.12	-9999	-0.21	237	237
RHOA	0.011	0	-9999	-10000	0	0
RAP1A/GTP	-0.097	0.11	-9999	-0.21	161	161
GRB7	-0.007	0.07	-9999	-0.28	31	31
RET51/GFRalpha1/GDNF	-0.1	0.13	-9999	-0.23	243	243
MAPKKK cascade	-0.098	0.11	-9999	-0.37	29	29
BCAR1	0.011	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.11	0.14	-9999	-0.24	252	252
lamellipodium assembly	-0.12	0.13	-9999	-0.24	245	245
RET51/GFRalpha1/GDNF/SHC	-0.1	0.13	-9999	-0.23	243	243
PIK3CA	0.01	0.019	-9999	-0.42	1	1
RET9/GFRalpha1/GDNF/SHC	-0.09	0.12	-9999	-0.21	237	237
RET9/GFRalpha1/GDNF/Shank3	-0.09	0.12	-9999	-0.21	237	237
MAPK3	-0.075	0.11	-9999	-0.34	27	27
DOK1	0.011	0	-9999	-10000	0	0
DOK6	-0.071	0.17	-9999	-0.42	98	98
PXN	0.011	0	-9999	-10000	0	0
neurite development	-0.082	0.12	-9999	-0.28	86	86
DOK5	-0.035	0.13	-9999	-0.41	55	55
GFRA1	-0.19	0.21	-9999	-0.42	238	238
MAPK8	-0.084	0.14	-9999	-0.41	30	30
HRAS/GTP	-0.11	0.13	-9999	-0.23	243	243
tube development	-0.079	0.11	-9999	-0.2	237	237
MAPK1	-0.075	0.11	-9999	-0.34	27	27
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.081	0.11	-9999	-0.2	236	236
Rac1/GDP	0.008	0	-9999	-10000	0	0
SRC	0.011	0	-9999	-10000	0	0
PDLIM7	0.011	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.13	0.16	-9999	-0.26	274	274
SHC1	0.011	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.1	0.13	-9999	-0.23	243	243
RET51/GFRalpha1/GDNF/Dok5	-0.12	0.16	-9999	-0.26	256	256
PRKCA	-0.017	0.1	-9999	-0.42	33	33
HRAS/GDP	0.008	0	-9999	-10000	0	0
CREB1	-0.1	0.14	-9999	-0.25	236	236
PIK3R1	0.007	0.038	-9999	-0.42	4	4
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.084	0.12	-9999	-0.21	236	236
RET51/GFRalpha1/GDNF/Grb7	-0.11	0.13	-9999	-0.24	246	246
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.022	0.11	-9999	-0.35	46	46
DOK4	0.011	0	-9999	-10000	0	0
JNK cascade	-0.075	0.13	-9999	-0.38	33	33
RET9/GFRalpha1/GDNF/FRS2	-0.09	0.12	-9999	-0.21	237	237
SHANK3	0.011	0	-9999	-10000	0	0
RASA1	0.006	0.042	-9999	-0.42	5	5
NCK1	0.009	0.027	-9999	-0.42	2	2
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.082	0.11	-9999	-0.2	236	236
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.09	0.13	-9999	-0.22	242	242
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.093	0.14	-9999	-0.22	243	243
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.094	0.14	-9999	-0.22	242	242
PI3K	-0.16	0.21	-9999	-0.36	245	245
SOS1	0.011	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.078	0.11	-9999	-0.2	237	237
GRB10	0.01	0.019	-9999	-0.42	1	1
activation of MAPKK activity	-0.082	0.11	-9999	-0.2	236	236
RET51/GFRalpha1/GDNF/FRS2	-0.1	0.13	-9999	-0.23	243	243
GAB1	0.007	0.038	-9999	-0.42	4	4
IRS1	-0.029	0.12	-9999	-0.42	47	47
IRS2	-0.045	0.14	-9999	-0.42	67	67
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.096	0.14	-9999	-0.23	242	242
RET51/GFRalpha1/GDNF/PKC alpha	-0.11	0.15	-9999	-0.25	253	253
GRB2	0.011	0	-9999	-10000	0	0
PRKACA	0.011	0	-9999	-10000	0	0
GDNF	0.004	0.018	-9999	-0.27	2	2
RAC1	0.011	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.12	0.16	-9999	-0.26	257	257
Rac1/GTP	-0.15	0.15	-9999	-0.29	245	245
RET9/GFRalpha1/GDNF	-0.11	0.13	-9999	-0.24	238	238
GFRalpha1/GDNF	-0.13	0.15	-9999	-0.29	238	238

×

Angiopoietin receptor Tie2-mediated 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
AKT1	-0.21	0.44	-10000	0	-0.84	168	168
NCK1/PAK1/Dok-R	-0.13	0.19	-10000	0	-0.4	168	168
NCK1/Dok-R	-0.28	0.51	-10000	0	-0.98	168	168
PIK3CA	0.01	0.019	-10000	0	-0.42	1	1
mol:beta2-estradiol	0.043	0.094	0.23	100	-10000	0	100
RELA	0.011	0	-10000	0	-10000	0	0
SHC1	0.01	0.002	-10000	0	-10000	0	0
Rac/GDP	0.008	0	-10000	0	-10000	0	0
F2	0.029	0.13	0.25	100	-0.28	38	138
TNIP2	0.011	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.3	0.45	-10000	0	-0.92	168	168
FN1	0.006	0.042	-10000	0	-0.42	5	5
PLD2	-0.3	0.54	-10000	0	-1	168	168
PTPN11	0.011	0	-10000	0	-10000	0	0
GRB14	-0.089	0.14	-10000	0	-0.27	179	179
ELK1	-0.26	0.48	-10000	0	-0.92	168	168
GRB7	-0.007	0.07	-10000	0	-0.28	31	31
PAK1	0.011	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.31	0.48	-10000	0	-0.96	168	168
CDKN1A	-0.13	0.31	-10000	0	-0.6	131	131
ITGA5	0.01	0.019	-10000	0	-0.42	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.28	0.51	-10000	0	-0.99	168	168
CRK	0.011	0	-10000	0	-10000	0	0
mol:NO	-0.14	0.34	-10000	0	-0.62	168	168
PLG	-0.32	0.54	-10000	0	-1.1	168	168
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.23	0.41	-10000	0	-0.81	168	168
GRB2	0.011	0	-10000	0	-10000	0	0
PIK3R1	0.007	0.038	-10000	0	-0.42	4	4
ANGPT2	-0.071	0.21	-10000	0	-0.56	40	40
BMX	-0.32	0.55	-10000	0	-1.1	168	168
ANGPT1	-0.22	0.48	-10000	0	-1.2	100	100
tube development	-0.15	0.34	-10000	0	-0.62	167	167
ANGPT4	0.002	0.032	-10000	0	-0.34	4	4
response to hypoxia	-0.019	0.032	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.3	0.58	-10000	0	-1.1	168	168
alpha5/beta1 Integrin	0.015	0.013	-10000	0	-0.29	1	1
FGF2	-0.24	0.21	-10000	0	-0.42	301	301
STAT5A (dimer)	-0.17	0.39	-10000	0	-0.7	167	167
mol:L-citrulline	-0.14	0.34	-10000	0	-0.62	168	168
AGTR1	-0.1	0.19	-10000	0	-0.41	136	136
MAPK14	-0.3	0.55	-10000	0	-1.1	168	168
Tie2/SHP2	-0.23	0.42	-10000	0	-1.1	99	99
TEK	-0.23	0.48	-10000	0	-1.2	99	99
RPS6KB1	-0.21	0.43	-10000	0	-0.81	168	168
Angiotensin II/AT1	-0.071	0.13	-10000	0	-0.29	136	136
Tie2/Ang1/GRB2	-0.31	0.55	-10000	0	-1.1	168	168
MAPK3	-0.27	0.49	-10000	0	-0.94	168	168
MAPK1	-0.27	0.49	-10000	0	-0.94	168	168
Tie2/Ang1/GRB7	-0.31	0.56	-10000	0	-1.1	168	168
NFKB1	0.01	0.019	-10000	0	-0.42	1	1
MAPK8	-0.3	0.54	-10000	0	-1	168	168
PI3K	-0.26	0.51	-10000	0	-0.97	168	168
FES	-0.3	0.54	-10000	0	-1	168	168
Crk/Dok-R	-0.28	0.51	-10000	0	-0.98	168	168
Tie2/Ang1/ABIN2	-0.31	0.55	-10000	0	-1.1	168	168
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.18	0.4	-10000	0	-0.75	168	168
STAT5A	0.011	0	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.21	0.43	-10000	0	-0.81	168	168
Tie2/Ang2	-0.22	0.46	-10000	0	-0.84	167	167
Tie2/Ang1	-0.33	0.59	-10000	0	-1.1	168	168
FOXO1	-0.18	0.4	-10000	0	-0.75	168	168
ELF1	-0.009	0.056	-10000	0	-0.44	4	4
ELF2	-0.3	0.54	-10000	0	-1	168	168
mol:Choline	-0.28	0.5	-10000	0	-0.98	168	168
cell migration	-0.074	0.11	-10000	0	-0.23	168	168
FYN	-0.17	0.38	-10000	0	-0.7	167	167
DOK2	0.008	0.029	-10000	0	-0.31	4	4
negative regulation of cell cycle	-0.11	0.28	-10000	0	-0.54	131	131
ETS1	-0.033	0.099	-10000	0	-0.22	101	101
PXN	-0.16	0.36	-10000	0	-0.67	168	168
ITGB1	0.011	0	-10000	0	-10000	0	0
NOS3	-0.17	0.38	-10000	0	-0.7	168	168
RAC1	0.011	0	-10000	0	-10000	0	0
TNF	-0.059	0.12	-10000	0	-0.25	144	144
MAPKKK cascade	-0.28	0.5	-10000	0	-0.98	168	168
RASA1	0.006	0.042	-10000	0	-0.42	5	5
Tie2/Ang1/Shc	-0.31	0.55	-10000	0	-1.1	168	168
NCK1	0.009	0.027	-10000	0	-0.42	2	2
vasculogenesis	-0.12	0.3	-10000	0	-0.55	168	168
mol:Phosphatidic acid	-0.28	0.5	-10000	0	-0.98	168	168
mol:Angiotensin II	0.001	0.001	-10000	0	-10000	0	0
mol:NADP	-0.14	0.34	-10000	0	-0.62	168	168
Rac1/GTP	-0.24	0.36	-10000	0	-0.75	168	168
MMP2	-0.3	0.54	-10000	0	-1	168	168

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.1	0.2	-10000	0	-0.4	115	115
PTK2B	0.01	0.001	-10000	0	-10000	0	0
mol:Ca2+	-0.13	0.31	-10000	0	-0.82	71	71
EDN1	-0.013	0.089	-10000	0	-0.37	13	13
EDN3	-0.081	0.14	-10000	0	-0.29	155	155
EDN2	-0.028	0.097	-10000	0	-0.27	69	69
HRAS/GDP	-0.13	0.21	-10000	0	-0.42	132	132
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.095	0.18	-10000	0	-0.37	120	120
ADCY4	-0.13	0.21	-10000	0	-0.42	138	138
ADCY5	-0.16	0.21	-10000	0	-0.43	152	152
ADCY6	-0.12	0.19	-10000	0	-0.4	127	127
ADCY7	-0.12	0.19	-10000	0	-0.4	121	121
ADCY1	-0.12	0.2	-10000	0	-0.41	134	134
ADCY2	-0.23	0.24	-10000	0	-0.46	217	217
ADCY3	-0.12	0.2	-10000	0	-0.4	129	129
ADCY8	-0.15	0.2	-10000	0	-0.41	143	143
ADCY9	-0.14	0.22	-10000	0	-0.44	146	146
arachidonic acid secretion	-0.19	0.28	-10000	0	-0.47	217	217
ETB receptor/Endothelin-1/Gq/GTP	-0.076	0.16	-10000	0	-0.28	164	164
GNAO1	-0.098	0.19	-10000	0	-0.42	131	131
HRAS	0.008	0.004	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	-0.081	0.2	-10000	0	-0.39	99	99
ETA receptor/Endothelin-1/Gs/GTP	-0.12	0.22	-10000	0	-0.42	127	127
mol:GTP	-0.002	0.005	-10000	0	-10000	0	0
COL3A1	-0.11	0.22	-10000	0	-0.49	90	90
EDNRB	-0.093	0.18	-10000	0	-0.42	126	126
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.14	0.26	-10000	0	-0.53	131	131
CYSLTR1	-0.11	0.23	-10000	0	-0.45	118	118
SLC9A1	-0.067	0.11	-10000	0	-0.27	72	72
mol:GDP	-0.14	0.23	-10000	0	-0.46	133	133
SLC9A3	-0.16	0.31	-10000	0	-0.62	135	135
RAF1	-0.17	0.25	-10000	0	-0.42	211	211
JUN	-0.11	0.26	-10000	0	-0.68	70	70
JAK2	-0.1	0.2	-10000	0	-0.4	123	123
mol:IP3	-0.1	0.18	-10000	0	-0.4	98	98
ETA receptor/Endothelin-1	-0.11	0.25	-10000	0	-0.46	125	125
PLCB1	0.005	0.033	-10000	0	-0.42	3	3
PLCB2	0.007	0.005	-10000	0	-10000	0	0
ETA receptor/Endothelin-3	-0.15	0.18	-10000	0	-0.34	211	211
FOS	-0.32	0.44	-10000	0	-0.89	182	182
Gai/GDP	-0.19	0.34	-10000	0	-0.74	132	132
CRK	0.01	0.001	-10000	0	-10000	0	0
mol:Ca ++	-0.16	0.26	-10000	0	-0.49	151	151
BCAR1	0.011	0	-10000	0	-10000	0	0
PRKCB1	-0.1	0.17	-10000	0	-0.38	102	102
GNAQ	0.006	0.027	-10000	0	-0.42	2	2
GNAZ	-0.011	0.094	-10000	0	-0.42	26	26
GNAL	-0.063	0.16	-10000	0	-0.42	88	88
Gs family/GDP	-0.18	0.2	-10000	0	-0.42	167	167
ETA receptor/Endothelin-1/Gq/GTP	-0.11	0.21	-10000	0	-0.4	131	131
MAPK14	-0.06	0.13	-10000	0	-0.3	84	84
TRPC6	-0.14	0.34	-10000	0	-0.9	70	70
GNAI2	0.011	0	-10000	0	-10000	0	0
GNAI3	0.011	0	-10000	0	-10000	0	0
GNAI1	0.002	0.059	-10000	0	-0.42	10	10
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.069	0.14	-10000	0	-0.3	106	106
ETB receptor/Endothelin-2	-0.082	0.15	-10000	0	-0.28	172	172
ETB receptor/Endothelin-3	-0.12	0.14	-10000	0	-0.25	262	262
ETB receptor/Endothelin-1	-0.07	0.15	-10000	0	-0.31	133	133
MAPK3	-0.28	0.39	-10000	0	-0.76	193	193
MAPK1	-0.28	0.39	-10000	0	-0.76	193	193
Rac1/GDP	-0.13	0.21	-10000	0	-0.42	132	132
cAMP biosynthetic process	-0.22	0.25	-10000	0	-0.46	221	221
MAPK8	-0.14	0.3	-10000	0	-0.75	79	79
SRC	0.01	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.099	0.18	-10000	0	-0.37	109	109
p130Cas/CRK/Src/PYK2	-0.12	0.23	-10000	0	-0.54	93	93
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.13	0.21	-10000	0	-0.42	132	132
COL1A2	-0.15	0.25	-10000	0	-0.53	122	122
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.12	0.18	-10000	0	-0.33	179	179
mol:DAG	-0.1	0.18	-10000	0	-0.4	98	98
MAP2K2	-0.22	0.3	-10000	0	-0.56	201	201
MAP2K1	-0.22	0.3	-10000	0	-0.56	202	202
EDNRA	-0.14	0.24	-10000	0	-0.47	156	156
positive regulation of muscle contraction	-0.082	0.18	-10000	0	-0.38	89	89
Gq family/GDP	-0.14	0.19	-10000	0	-0.45	110	110
HRAS/GTP	-0.14	0.21	-10000	0	-0.42	137	137
PRKCH	-0.097	0.18	-10000	0	-0.41	90	90
RAC1	0.011	0	-10000	0	-10000	0	0
PRKCA	-0.11	0.19	-10000	0	-0.41	106	106
PRKCB	-0.11	0.19	-10000	0	-0.42	104	104
PRKCE	-0.095	0.17	-10000	0	-0.4	89	89
PRKCD	-0.097	0.17	-10000	0	-0.39	98	98
PRKCG	-0.12	0.18	-10000	0	-0.4	112	112
regulation of vascular smooth muscle contraction	-0.38	0.51	-10000	0	-1	181	181
PRKCQ	-0.11	0.18	-10000	0	-0.4	111	111
PLA2G4A	-0.21	0.31	-10000	0	-0.51	217	217
GNA14	-0.036	0.13	-10000	0	-0.42	53	53
GNA15	0.004	0.033	-10000	0	-0.28	7	7
GNA12	0.011	0	-10000	0	-10000	0	0
GNA11	-0.001	0.062	-10000	0	-0.42	11	11
Rac1/GTP	-0.081	0.2	-10000	0	-0.4	95	95
MMP1	0.016	0.14	0.27	13	-10000	0	13

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.016	0	-10000	0	-10000	0	0
Necdin/E2F1	-0.16	0.17	-10000	0	-0.31	280	280
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.087	0.15	-10000	0	-0.24	223	223
NGF (dimer)/p75(NTR)/BEX1	-0.16	0.2	-10000	0	-0.33	262	262
NT-4/5 (dimer)/p75(NTR)	-0.09	0.14	-10000	0	-0.28	180	180
IKBKB	0.011	0	-10000	0	-10000	0	0
AKT1	-0.087	0.14	-10000	0	-0.24	222	222
IKBKG	0.011	0	-10000	0	-10000	0	0
BDNF	-0.028	0.096	-10000	0	-0.27	69	69
MGDIs/NGR/p75(NTR)/LINGO1	-0.065	0.12	-10000	0	-0.24	168	168
FURIN	0.011	0	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.083	0.12	-10000	0	-0.24	167	167
LINGO1	0.005	0.04	-10000	0	-0.29	9	9
Sortilin/TRAF6/NRIF	-0.001	0.013	-10000	0	-10000	0	0
proBDNF (dimer)	-0.028	0.096	-10000	0	-0.27	69	69
NTRK1	0	0.059	-10000	0	-0.34	14	14
RTN4R	0.01	0.019	-10000	0	-0.42	1	1
neuron apoptosis	-0.084	0.14	-10000	0	-0.35	64	64
IRAK1	0.011	0	-10000	0	-10000	0	0
SHC1	-0.11	0.17	-10000	0	-0.29	219	219
ARHGDIA	0.011	0	-10000	0	-10000	0	0
RhoA/GTP	0.008	0	-10000	0	-10000	0	0
Gamma Secretase	0.03	0.019	-10000	0	-0.18	4	4
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.15	0.19	-10000	0	-0.3	273	273
MAGEH1	-0.086	0.18	-10000	0	-0.42	116	116
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.2	0.2	-10000	0	-0.32	333	333
Mammalian IAPs/DIABLO	0.023	0.031	-10000	0	-0.2	9	9
proNGF (dimer)	-0.082	0.18	-10000	0	-0.42	111	111
MAGED1	0.009	0.027	-10000	0	-0.42	2	2
APP	0.011	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.001	0.053	-10000	0	-0.3	15	15
ZNF274	0.011	0	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.09	0.14	-10000	0	-0.24	219	219
NGF	-0.082	0.18	-10000	0	-0.42	111	111
cell cycle arrest	-0.081	0.14	0.14	41	-0.34	68	109
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.091	0.15	-10000	0	-0.25	219	219
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.068	0.12	-10000	0	-0.24	170	170
NCSTN	0.011	0	-10000	0	-10000	0	0
mol:GTP	-0.12	0.17	-10000	0	-0.29	223	223
PSENEN	0.011	0	-10000	0	-10000	0	0
mol:ceramide	-0.096	0.15	-10000	0	-0.26	219	219
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.072	0.13	-10000	0	-0.35	59	59
p75(NTR)/beta APP	-0.083	0.14	-10000	0	-0.28	168	168
BEX1	-0.073	0.17	-10000	0	-0.42	100	100
mol:GDP	-0.12	0.17	-10000	0	-0.3	220	220
NGF (dimer)	-0.086	0.15	-10000	0	-0.26	185	185
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.051	0.11	-10000	0	-0.21	168	168
PIK3R1	0.007	0.038	-10000	0	-0.42	4	4
RAC1/GTP	-0.096	0.14	-10000	0	-0.25	219	219
MYD88	0.011	0	-10000	0	-10000	0	0
CHUK	0.011	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.12	0.17	-10000	0	-0.3	223	223
RHOB	0.009	0.027	-10000	0	-0.42	2	2
RHOA	0.011	0	-10000	0	-10000	0	0
MAGE-G1/E2F1	-0.025	0.078	-10000	0	-0.18	109	109
NT3 (dimer)	-0.023	0.11	-10000	0	-0.41	40	40
TP53	-0.05	0.098	-10000	0	-0.27	11	11
PRDM4	-0.097	0.15	-10000	0	-0.26	219	219
BDNF (dimer)	-0.071	0.13	-10000	0	-0.27	123	123
PIK3CA	0.01	0.019	-10000	0	-0.42	1	1
SORT1	0.011	0	-10000	0	-10000	0	0
activation of caspase activity	-0.1	0.13	-10000	0	-0.24	223	223
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.096	0.16	-10000	0	-0.26	219	219
RHOC	0.011	0	-10000	0	-10000	0	0
XIAP	0.011	0	-10000	0	-10000	0	0
MAPK10	-0.13	0.18	-10000	0	-0.33	196	196
DIABLO	0.011	0	-10000	0	-10000	0	0
SMPD2	-0.097	0.15	-10000	0	-0.26	219	219
APH1B	0.007	0.038	-10000	0	-0.42	4	4
APH1A	0.011	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.11	0.17	-10000	0	-0.29	219	219
PSEN1	0.011	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.016	0	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.1	0.16	-10000	0	-0.31	190	190
MAPK8	-0.09	0.15	-10000	0	-0.27	173	173
MAPK9	-0.088	0.15	-10000	0	-0.27	172	172
APAF1	0.011	0	-10000	0	-10000	0	0
NTF3	-0.023	0.11	-10000	0	-0.41	40	40
NTF4	-0.001	0.053	-10000	0	-0.3	15	15
NDN	-0.19	0.21	-10000	0	-0.42	240	240
RAC1/GDP	0.008	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.096	0.12	-10000	0	-0.36	62	62
p75 CTF/Sortilin/TRAF6/NRIF	0.027	0	-10000	0	-10000	0	0
RhoA-B-C/GTP	-0.12	0.17	-10000	0	-0.29	223	223
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.057	0.1	-10000	0	-0.19	167	167
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.067	0.11	-10000	0	-0.21	167	167
PRKACB	0.006	0.046	-10000	0	-0.42	6	6
proBDNF (dimer)/p75 ECD	-0.01	0.065	-10000	0	-0.18	69	69
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.003	0.057	-10000	0	-0.4	10	10
BIRC2	0.011	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.19	0.2	0.15	17	-0.36	243	260
BAD	-0.11	0.16	-10000	0	-0.3	188	188
RIPK2	0.011	0	-10000	0	-10000	0	0
NGFR	-0.13	0.2	-10000	0	-0.42	168	168
CYCS	-0.086	0.14	-10000	0	-0.24	221	221
ADAM17	0.011	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.096	0.16	-10000	0	-0.26	219	219
BCL2L11	-0.11	0.16	-10000	0	-0.3	188	188
BDNF (dimer)/p75(NTR)	-0.11	0.14	-10000	0	-0.26	228	228
PI3K	-0.098	0.16	-10000	0	-0.26	222	222
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.096	0.16	-10000	0	-0.26	219	219
NDNL2	0.011	0	-10000	0	-10000	0	0
YWHAE	0.011	0	-10000	0	-10000	0	0
PRKCI	0.011	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.14	0.2	-10000	0	-0.35	220	220
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.097	0.16	-10000	0	-0.26	221	221
TRAF6	0.011	0	-10000	0	-10000	0	0
RAC1	0.011	0	-10000	0	-10000	0	0
PRKCZ	0.009	0.023	-10000	0	-0.34	2	2
PLG	-0.053	0.15	-10000	0	-0.41	76	76
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.11	0.16	-10000	0	-0.28	219	219
SQSTM1	0.011	0	-10000	0	-10000	0	0
NGFRAP1	0.006	0.042	-10000	0	-0.42	5	5
CASP3	-0.099	0.16	-10000	0	-0.28	188	188
E2F1	-0.05	0.12	-10000	0	-0.27	109	109
CASP9	0.011	0	-10000	0	-10000	0	0
IKK complex	-0.095	0.13	-10000	0	-0.31	118	118
NGF (dimer)/TRKA	-0.057	0.13	-10000	0	-0.28	123	123
MMP7	-0.048	0.13	-10000	0	-0.33	88	88
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.085	0.15	-10000	0	-0.24	219	219
MMP3	-0.02	0.09	-10000	0	-0.28	53	53
APAF-1/Caspase 9	-0.074	0.096	-10000	0	-0.29	60	60

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.11	0.19	-9999	-0.44	133	133
PDGF/PDGFRA/CRKL	-0.068	0.13	-9999	-0.29	133	133
positive regulation of JUN kinase activity	-0.036	0.099	-9999	-0.2	133	133
CRKL	0.011	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.075	0.13	-9999	-0.3	134	134
AP1	-0.32	0.4	-9999	-0.87	174	174
mol:IP3	-0.08	0.14	-9999	-0.31	133	133
PLCG1	-0.08	0.14	-9999	-0.31	133	133
PDGF/PDGFRA/alphaV Integrin	-0.068	0.13	-9999	-0.29	133	133
RAPGEF1	0.011	0	-9999	-10000	0	0
CRK	0.011	0	-9999	-10000	0	0
mol:Ca2+	-0.08	0.14	-9999	-0.31	133	133
CAV3	0.002	0.013	-9999	-0.27	1	1
CAV1	-0.082	0.18	-9999	-0.42	111	111
SHC/Grb2/SOS1	-0.036	0.1	-9999	-0.2	133	133
PDGF/PDGFRA/Shf	-0.07	0.14	-9999	-0.3	133	133
FOS	-0.3	0.41	-9999	-0.86	174	174
JUN	-0.027	0.045	-9999	-0.36	6	6
oligodendrocyte development	-0.068	0.13	-9999	-0.29	133	133
GRB2	0.011	0	-9999	-10000	0	0
PIK3R1	0.007	0.038	-9999	-0.42	4	4
mol:DAG	-0.08	0.14	-9999	-0.31	133	133
PDGF/PDGFRA	-0.11	0.19	-9999	-0.44	133	133
actin cytoskeleton reorganization	-0.068	0.13	-9999	-0.29	133	133
SRF	0.025	0.012	-9999	-10000	0	0
SHC1	0.011	0	-9999	-10000	0	0
PI3K	-0.05	0.11	-9999	-0.24	135	135
PDGF/PDGFRA/Crk/C3G	-0.048	0.11	-9999	-0.23	133	133
JAK1	-0.068	0.14	-9999	-0.3	133	133
ELK1/SRF	-0.046	0.11	-9999	-0.23	133	133
SHB	0.011	0	-9999	-10000	0	0
SHF	0.007	0.038	-9999	-0.42	4	4
CSNK2A1	0.022	0.025	-9999	-10000	0	0
GO:0007205	-0.089	0.15	-9999	-0.34	133	133
SOS1	0.011	0	-9999	-10000	0	0
Ras protein signal transduction	-0.036	0.099	-9999	-0.2	133	133
PDGF/PDGFRA/SHB	-0.068	0.13	-9999	-0.29	133	133
PDGF/PDGFRA/Caveolin-1	-0.13	0.2	-9999	-0.37	188	188
ITGAV	0.011	0	-9999	-10000	0	0
ELK1	-0.082	0.14	-9999	-0.3	133	133
PIK3CA	0.01	0.019	-9999	-0.42	1	1
PDGF/PDGFRA/Crk	-0.068	0.13	-9999	-0.29	133	133
JAK-STAT cascade	-0.068	0.14	-9999	-0.3	133	133
cell proliferation	-0.07	0.14	-9999	-0.3	133	133

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.001	0.068	-9999	-0.29	28	28
alphaV beta3 Integrin	-0.18	0.17	-9999	-0.29	322	322
PTK2	-0.16	0.2	-9999	-0.43	148	148
IGF1R	-0.006	0.083	-9999	-0.42	20	20
PI4KB	0.011	0	-9999	-10000	0	0
MFGE8	0.009	0.027	-9999	-0.42	2	2
SRC	0.011	0	-9999	-10000	0	0
CDKN1B	-0.15	0.22	-9999	-0.56	97	97
VEGFA	0.011	0	-9999	-10000	0	0
ILK	-0.13	0.19	-9999	-0.56	73	73
ROCK1	0.011	0	-9999	-10000	0	0
AKT1	-0.12	0.18	-9999	-0.52	73	73
PTK2B	-0.026	0.1	-9999	-0.21	119	119
alphaV/beta3 Integrin/JAM-A	-0.17	0.17	-9999	-0.27	341	341
CBL	0.011	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.035	0.1	-9999	-0.24	105	105
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.047	0.14	-9999	-0.27	130	130
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.046	0.12	-9999	-0.36	30	30
alphaV/beta3 Integrin/Syndecan-1	-0.085	0.12	-9999	-0.26	106	106
PI4KA	0.011	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.2	0.18	-9999	-0.43	162	162
PI4 Kinase	0.016	0	-9999	-10000	0	0
PIK3CA	0.01	0.019	-9999	-0.42	1	1
alphaV/beta3 Integrin/Osteopontin	-0.072	0.11	-9999	-0.25	106	106
RPS6KB1	-0.17	0.19	-9999	-0.4	162	162
TLN1	0.011	0	-9999	-10000	0	0
MAPK3	-0.32	0.28	-9999	-0.51	322	322
GPR124	-0.08	0.18	-9999	-0.42	109	109
MAPK1	-0.32	0.28	-9999	-0.51	322	322
PXN	0.011	0	-9999	-10000	0	0
PIK3R1	0.007	0.038	-9999	-0.42	4	4
alphaV/beta3 Integrin/Tumstatin	-0.068	0.14	-9999	-0.26	153	153
cell adhesion	-0.028	0.1	-9999	-0.23	105	105
ANGPTL3	0.004	0.018	-9999	-0.27	2	2
VEGFR2 homodimer/VEGFA homodimer/Src	0.008	0.058	-9999	-0.23	28	28
IGF-1R heterotetramer	-0.006	0.083	-9999	-0.42	20	20
Rac1/GDP	0.008	0	-9999	-10000	0	0
TGFBR2	0	0.067	-9999	-0.42	13	13
ITGB3	-0.078	0.17	-9999	-0.41	107	107
IGF1	-0.074	0.17	-9999	-0.42	102	102
RAC1	0.011	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.083	0.15	-9999	-0.28	176	176
apoptosis	0.011	0	-9999	-10000	0	0
CD47	0.011	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.031	0.1	-9999	-0.23	105	105
VCL	0.011	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.11	0.17	-9999	-0.3	209	209
CSF1	0.002	0.059	-9999	-0.42	10	10
PIK3C2A	-0.13	0.19	-9999	-0.37	144	144
PI4 Kinase/Pyk2	-0.15	0.14	-9999	-0.36	138	138
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.032	0.11	-9999	-0.23	119	119
FAK1/Vinculin	-0.12	0.16	-9999	-0.34	140	140
alphaV beta3/Integrin/ppsTEM5	-0.083	0.15	-9999	-0.28	176	176
RHOA	0.011	0	-9999	-10000	0	0
VTN	-0.053	0.15	-9999	-0.41	76	76
BCAR1	0.011	0	-9999	-10000	0	0
FGF2	-0.24	0.21	-9999	-0.42	301	301
F11R	-0.16	0.15	-9999	-0.29	302	302
alphaV/beta3 Integrin/Lactadherin	-0.032	0.1	-9999	-0.24	105	105
alphaV/beta3 Integrin/TGFBR2	-0.037	0.12	-9999	-0.25	108	108
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.023	0.032	-9999	-0.2	10	10
HSP90AA1	0.011	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.027	0.093	-9999	-0.21	105	105
mol:GDP	0	0	-9999	-10000	0	0
FN1	0.006	0.042	-9999	-0.42	5	5
alphaV/beta3 Integrin/Pyk2	-0.025	0.11	-9999	-0.21	119	119
SDC1	-0.088	0.14	-9999	-0.27	179	179
VAV3	-0.008	0.064	-9999	-0.21	10	10
PTPN11	0.011	0	-9999	-10000	0	0
IRS1	-0.029	0.12	-9999	-0.42	47	47
FAK1/Paxillin	-0.12	0.16	-9999	-0.34	140	140
cell migration	-0.11	0.14	-9999	-0.31	140	140
ITGAV	0.011	0	-9999	-10000	0	0
PI3K	-0.16	0.14	-9999	-0.37	130	130
SPP1	-0.063	0.12	-9999	-0.27	134	134
KDR	-0.013	0.097	-9999	-0.42	28	28
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.011	0	-9999	-10000	0	0
COL4A3	-0.054	0.15	-9999	-0.4	79	79
angiogenesis	-0.32	0.28	-9999	-0.51	323	323
Rac1/GTP	-0.001	0.058	-9999	-0.28	2	2
EDIL3	-0.12	0.2	-9999	-0.42	161	161
cell proliferation	-0.037	0.12	-9999	-0.25	108	108

×

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	0.008	0.001	-10000	0	-10000	0	0
GNB1/GNG2	-0.028	0.095	-10000	0	-0.22	102	102
regulation of S phase of mitotic cell cycle	-0.02	0.088	-10000	0	-0.21	93	93
GNAO1	-0.099	0.19	-10000	0	-0.42	131	131
HRAS	0.01	0.002	-10000	0	-10000	0	0
SHBG/T-DHT	0.005	0.019	-10000	0	-0.25	3	3
PELP1	0.01	0.002	-10000	0	-10000	0	0
AKT1	0.009	0.001	-10000	0	-10000	0	0
MAP2K1	-0.038	0.094	-10000	0	-0.27	35	35
T-DHT/AR	-0.047	0.12	-10000	0	-0.3	90	90
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.002	0.003	-10000	0	-0.007	174	174
GNAI2	0.01	0	-10000	0	-10000	0	0
GNAI3	0.01	0	-10000	0	-10000	0	0
GNAI1	0.002	0.059	-10000	0	-0.42	10	10
mol:GDP	-0.061	0.14	-10000	0	-0.35	91	91
cell proliferation	-0.12	0.2	-10000	0	-0.39	174	174
PIK3CA	0.01	0.019	-10000	0	-0.42	1	1
FOS	-0.24	0.38	-10000	0	-0.77	174	174
mol:Ca2+	-0.025	0.031	-10000	0	-0.063	171	171
MAPK3	-0.083	0.15	-10000	0	-0.27	174	174
MAPK1	-0.058	0.1	-10000	0	-0.22	76	76
PIK3R1	0.007	0.038	-10000	0	-0.42	4	4
mol:IP3	-0.001	0.002	-10000	0	-0.004	174	174
cAMP biosynthetic process	0.013	0.03	0.094	9	-0.2	3	12
GNG2	-0.002	0.071	-10000	0	-0.41	15	15
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.004	174	174
HRAS/GTP	-0.044	0.074	-10000	0	-0.2	90	90
actin cytoskeleton reorganization	-0.002	0.018	-10000	0	-0.18	5	5
SRC	0.01	0.002	-10000	0	-10000	0	0
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.004	174	174
PI3K	0.012	0.025	-10000	0	-0.24	5	5
apoptosis	0.12	0.21	0.4	174	-10000	0	174
T-DHT/AR/PELP1	-0.034	0.097	-10000	0	-0.24	90	90
HRAS/GDP	-0.058	0.13	-10000	0	-0.34	90	90
CREB1	-0.13	0.22	-10000	0	-0.43	174	174
RAC1-CDC42/GTP	0.002	0.02	-10000	0	-0.18	5	5
AR	-0.066	0.16	-10000	0	-0.42	90	90
GNB1	0.011	0	-10000	0	-10000	0	0
RAF1	-0.034	0.088	-10000	0	-0.2	90	90
RAC1-CDC42/GDP	-0.051	0.12	-10000	0	-0.32	90	90
T-DHT/AR/PELP1/Src	-0.027	0.089	-10000	0	-0.22	90	90
MAP2K2	-0.038	0.094	-10000	0	-0.27	35	35
T-DHT/AR/PELP1/Src/PI3K	-0.021	0.089	-10000	0	-0.21	93	93
GNAZ	-0.011	0.094	-10000	0	-0.42	26	26
SHBG	0.008	0.033	-10000	0	-0.42	3	3
Gi family/GNB1/GNG2/GDP	-0.079	0.17	-10000	0	-0.33	135	135
mol:T-DHT	-0.001	0.001	-10000	0	-0.003	139	139
RAC1	0.011	0	-10000	0	-10000	0	0
GNRH1	0.005	0.032	-10000	0	-0.29	6	6
Gi family/GTP	-0.065	0.12	-10000	0	-0.27	93	93
CDC42	0.011	0	-10000	0	-10000	0	0

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	-0.005	0.081	-10000	0	-0.42	19	19
ANTXR2	-0.13	0.2	-10000	0	-0.42	167	167
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.02	0.028	-10000	0	-0.059	171	171
monocyte activation	-0.028	0.12	-10000	0	-0.41	42	42
MAP2K2	-0.007	0.011	-10000	0	-10000	0	0
MAP2K1	-0.016	0.023	-10000	0	-10000	0	0
MAP2K7	-0.016	0.023	-10000	0	-0.079	15	15
MAP2K6	-0.032	0.046	-10000	0	-0.12	80	80
CYAA	-0.065	0.11	-10000	0	-0.22	171	171
MAP2K4	-0.017	0.026	-10000	0	-0.09	16	16
IL1B	-0.012	0.044	-10000	0	-0.15	30	30
Channel	-0.069	0.12	-10000	0	-0.23	171	171
NLRP1	-0.026	0.054	-10000	0	-0.24	24	24
CALM1	0.011	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.021	0.031	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.02	0.028	0.059	171	-10000	0	171
MAPK3	-0.016	0.023	-10000	0	-10000	0	0
MAPK1	-0.016	0.023	-10000	0	-10000	0	0
PGR	-0.079	0.1	-10000	0	-0.23	154	154
PA/Cellular Receptors	-0.077	0.13	-10000	0	-0.26	171	171
apoptosis	-0.02	0.028	-10000	0	-0.059	171	171
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.065	0.12	-10000	0	-0.22	171	171
macrophage activation	-0.004	0.026	-10000	0	-10000	0	0
TNF	-0.018	0.086	-10000	0	-0.28	50	50
VCAM1	-0.029	0.12	-10000	0	-0.41	42	42
platelet activation	-0.021	0.031	-10000	0	-10000	0	0
MAPKKK cascade	0.013	0.031	0.082	32	-10000	0	32
IL18	-0.012	0.042	-10000	0	-0.14	34	34
negative regulation of macrophage activation	-0.02	0.028	-10000	0	-0.059	171	171
LEF	-0.02	0.028	-10000	0	-0.059	171	171
CASP1	-0.022	0.038	-10000	0	-0.12	42	42
mol:cAMP	-0.021	0.031	-10000	0	-10000	0	0
necrosis	-0.02	0.028	-10000	0	-0.059	171	171
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.064	0.12	-10000	0	-0.22	171	171
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.007	0.085	-9999	-0.42	21	21
mol:S1P	-0.01	0.014	-9999	-10000	0	0
S1P1/S1P/Gi	-0.083	0.13	-9999	-0.28	112	112
GNAO1	-0.11	0.19	-9999	-0.43	131	131
S1P/S1P3/G12/G13	0.002	0.045	-9999	-0.22	17	17
AKT1	-0.068	0.16	-9999	-0.59	29	29
AKT3	-0.46	0.56	-9999	-1.1	212	212
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.007	0.085	-9999	-0.42	21	21
GNAI2	0	0.015	-9999	-10000	0	0
GNAI3	0.003	0.011	-9999	-10000	0	0
GNAI1	-0.005	0.061	-9999	-0.43	10	10
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	-0.014	0.078	-9999	-0.43	17	17
S1PR2	0.011	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	-0.15	0.2	-9999	-0.34	218	218
MAPK3	-0.14	0.19	-9999	-0.32	218	218
MAPK1	-0.14	0.19	-9999	-0.32	218	218
JAK2	-0.14	0.2	-9999	-0.33	218	218
CXCR4	-0.14	0.19	-9999	-0.32	218	218
FLT1	0	0.025	-9999	-0.43	1	1
RhoA/GDP	0.008	0	-9999	-10000	0	0
Rac1/GDP	0.008	0	-9999	-10000	0	0
SRC	-0.14	0.19	-9999	-0.32	218	218
S1P/S1P3/Gi	-0.15	0.2	-9999	-0.34	218	218
RAC1	0.011	0	-9999	-10000	0	0
RhoA/GTP	-0.13	0.19	-9999	-0.31	218	218
VEGFA	0.001	0.017	-9999	-10000	0	0
S1P/S1P2/Gi	-0.095	0.14	-9999	-0.29	139	139
VEGFR1 homodimer/VEGFA homodimer	-0.004	0.035	-9999	-0.31	1	1
RHOA	0.011	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.022	0.099	-9999	-0.25	73	73
GNAQ	0.009	0.027	-9999	-0.42	2	2
GNAZ	-0.019	0.094	-9999	-0.42	26	26
G12/G13	0.016	0	-9999	-10000	0	0
GNA14	-0.034	0.13	-9999	-0.42	53	53
GNA15	0.007	0.033	-9999	-0.27	7	7
GNA12	0.011	0	-9999	-10000	0	0
GNA13	0.011	0	-9999	-10000	0	0
GNA11	0.001	0.062	-9999	-0.42	11	11
Rac1/GTP	-0.13	0.19	-9999	-0.31	218	218

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.011	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.1	0.048	-9999	-0.26	2	2
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.028	0.011	-9999	-10000	0	0
AURKB	-0.24	0.095	-9999	-0.27	447	447
AURKC	0.01	0.018	-9999	-0.27	2	2

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.055	0.19	-10000	0	-0.6	45	45
IHH	-0.13	0.19	-10000	0	-0.34	205	205
SHH Np/Cholesterol/GAS1	-0.14	0.12	-10000	0	-0.23	327	327
LRPAP1	0.011	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.14	0.12	0.23	327	-10000	0	327
SMO/beta Arrestin2	-0.044	0.15	-10000	0	-0.43	21	21
SMO	-0.052	0.16	-10000	0	-0.37	45	45
AKT1	-0.013	0.091	-10000	0	-0.48	4	4
ARRB2	0.011	0	-10000	0	-10000	0	0
BOC	-0.015	0.1	-10000	0	-0.42	31	31
ADRBK1	0.011	0	-10000	0	-10000	0	0
heart looping	-0.051	0.16	-10000	0	-0.36	45	45
STIL	-0.047	0.11	-10000	0	-0.32	33	33
DHH N/PTCH2	-0.023	0.11	-10000	0	-0.3	62	62
DHH N/PTCH1	-0.062	0.14	-10000	0	-0.36	42	42
PIK3CA	0.01	0.019	-10000	0	-0.42	1	1
DHH	-0.023	0.11	-10000	0	-0.42	40	40
PTHLH	-0.069	0.22	-10000	0	-0.6	46	46
determination of left/right symmetry	-0.051	0.16	-10000	0	-0.36	45	45
PIK3R1	0.007	0.038	-10000	0	-0.42	4	4
skeletal system development	-0.068	0.21	-10000	0	-0.6	46	46
IHH N/Hhip	-0.042	0.14	-10000	0	-0.26	141	141
DHH N/Hhip	-0.024	0.095	-10000	0	-0.24	78	78
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.051	0.16	-10000	0	-0.36	45	45
pancreas development	-0.013	0.08	-10000	0	-0.29	40	40
HHAT	0.008	0.033	-10000	0	-0.42	3	3
PI3K	0.013	0.03	-10000	0	-0.29	5	5
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.26	0.21	-10000	0	-0.42	325	325
somite specification	-0.051	0.16	-10000	0	-0.36	45	45
SHH Np/Cholesterol/PTCH1	-0.043	0.11	-10000	0	-0.34	26	26
SHH Np/Cholesterol/PTCH2	-0.011	0.071	-10000	0	-0.23	29	29
SHH Np/Cholesterol/Megalin	-0.052	0.084	-10000	0	-0.26	28	28
SHH	-0.009	0.067	-10000	0	-0.18	64	64
catabolic process	-0.057	0.14	-10000	0	-0.34	46	46
SMO/Vitamin D3	-0.037	0.14	-10000	0	-0.37	28	28
SHH Np/Cholesterol/Hhip	-0.012	0.064	-10000	0	-0.24	13	13
LRP2	-0.094	0.14	-10000	0	-0.27	189	189
receptor-mediated endocytosis	-0.063	0.13	-10000	0	-0.38	26	26
SHH Np/Cholesterol/BOC	-0.014	0.074	-10000	0	-0.23	34	34
SHH Np/Cholesterol/CDO	-0.038	0.1	-10000	0	-0.23	90	90
mesenchymal cell differentiation	0.012	0.063	0.23	13	-10000	0	13
mol:Vitamin D3	-0.031	0.12	-10000	0	-0.34	26	26
IHH N/PTCH2	-0.036	0.15	-10000	0	-0.28	126	126
CDON	-0.062	0.16	-10000	0	-0.42	87	87
IHH N/PTCH1	-0.023	0.16	-10000	0	-0.34	46	46
Megalin/LRPAP1	-0.055	0.091	-10000	0	-0.18	189	189
PTCH2	-0.011	0.094	-10000	0	-0.42	26	26
SHH Np/Cholesterol	-0.007	0.049	-10000	0	-0.13	64	64
PTCH1	-0.057	0.14	-10000	0	-0.34	46	46
HHIP	-0.013	0.081	-10000	0	-0.29	40	40

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.015	0.008	-9999	-0.18	1	1
VLDLR	0.009	0.027	-9999	-0.42	2	2
CRKL	0.011	0	-9999	-10000	0	0
LRPAP1	0.011	0	-9999	-10000	0	0
FYN	0.011	0	-9999	-10000	0	0
ITGA3	0.01	0.019	-9999	-0.42	1	1
RELN/VLDLR/Fyn	-0.074	0.12	-9999	-0.23	187	187
MAPK8IP1/MKK7/MAP3K11/JNK1	0.029	0.024	-9999	-0.18	6	6
AKT1	-0.054	0.1	-9999	-0.18	192	192
MAP2K7	0.011	0	-9999	-10000	0	0
RAPGEF1	0.011	0	-9999	-10000	0	0
DAB1	0.001	0.043	-9999	-0.27	12	12
RELN/LRP8/DAB1	-0.071	0.11	-9999	-0.21	188	188
LRPAP1/LRP8	0.014	0.017	-9999	-0.18	4	4
RELN/LRP8/DAB1/Fyn	-0.061	0.1	-9999	-0.19	188	188
DAB1/alpha3/beta1 Integrin	-0.064	0.081	-9999	-0.3	5	5
long-term memory	-0.14	0.15	-9999	-0.37	111	111
DAB1/LIS1	-0.067	0.085	-9999	-0.28	5	5
DAB1/CRLK/C3G	-0.063	0.08	-9999	-0.26	5	5
PIK3CA	0.01	0.019	-9999	-0.42	1	1
DAB1/NCK2	-0.068	0.085	-9999	-0.28	5	5
ARHGEF2	0.011	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.18	0.21	-9999	-0.42	224	224
CDK5R1	0.01	0.012	-9999	-0.27	1	1
RELN	-0.15	0.2	-9999	-0.41	191	191
PIK3R1	0.007	0.038	-9999	-0.42	4	4
RELN/LRP8/Fyn	-0.074	0.12	-9999	-0.23	187	187
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.15	0.15	-9999	-0.25	315	315
MAPK8	0.006	0.042	-9999	-0.42	5	5
RELN/VLDLR/DAB1	-0.071	0.11	-9999	-0.21	188	188
ITGB1	0.011	0	-9999	-10000	0	0
MAP1B	-0.071	0.12	-9999	-0.21	207	207
RELN/LRP8	-0.074	0.12	-9999	-0.23	187	187
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.062	0.1	-9999	-0.19	189	189
PI3K	0.013	0.03	-9999	-0.29	5	5
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	0.015	0.013	-9999	-0.29	1	1
RAP1A	-0.034	0.093	-9999	-0.29	3	3
PAFAH1B1	0.011	0	-9999	-10000	0	0
MAPK8IP1	0.009	0.023	-9999	-0.34	2	2
CRLK/C3G	0.016	0	-9999	-10000	0	0
GRIN2B	-0.005	0.053	-9999	-0.27	19	19
NCK2	0.011	0	-9999	-10000	0	0
neuron differentiation	-0.033	0.084	-9999	-0.37	1	1
neuron adhesion	-0.023	0.091	-9999	-0.32	3	3
LRP8	0.008	0.025	-9999	-0.27	4	4
GSK3B	-0.046	0.097	-9999	-0.18	77	77
RELN/VLDLR/DAB1/Fyn	-0.061	0.1	-9999	-0.19	188	188
MAP3K11	0.011	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.064	0.11	-9999	-0.2	192	192
CDK5	0.011	0	-9999	-10000	0	0
MAPT	0.001	0.079	-9999	-0.38	20	20
neuron migration	-0.054	0.13	-9999	-0.23	186	186
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.033	0.084	-9999	-0.37	1	1
RELN/VLDLR	-0.06	0.11	-9999	-0.21	188	188

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.002	0.063	-9999	-0.24	34	34
ADCY5	-0.034	0.1	-9999	-0.24	99	99
ADCY6	0.015	0	-9999	-10000	0	0
ADCY7	0.015	0	-9999	-10000	0	0
ADCY1	0.004	0.049	-9999	-0.21	25	25
ADCY2	-0.13	0.13	-9999	-0.24	286	286
ADCY3	0.014	0.016	-9999	-0.24	2	2
ADCY8	-0.02	0.079	-9999	-0.24	59	59
PRKCE	0.009	0	-9999	-10000	0	0
ADCY9	-0.018	0.085	-9999	-0.24	65	65
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.079	0.089	-9999	-0.19	144	144

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.1	0.34	-9999	-0.96	68	68
MKNK1	0.011	0	-9999	-10000	0	0
MAPK14	-0.018	0.1	-9999	-0.27	72	72
ATF2/c-Jun	-0.007	0.11	-9999	-0.5	9	9
MAPK11	-0.02	0.11	-9999	-0.27	74	74
MITF	-0.051	0.17	-9999	-0.38	82	82
MAPKAPK5	-0.016	0.12	-9999	-0.32	74	74
KRT8	-0.029	0.13	-9999	-0.33	76	76
MAPKAPK3	0.011	0	-9999	-10000	0	0
MAPKAPK2	0.011	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.028	0.15	-9999	-0.39	72	72
CEBPB	-0.016	0.12	-9999	-0.32	74	74
SLC9A1	-0.016	0.12	-9999	-0.32	74	74
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.014	0.13	-9999	-0.31	77	77
p38alpha-beta/MNK1	-0.012	0.12	-9999	-0.3	72	72
JUN	-0.007	0.11	-9999	-0.63	6	6
PPARGC1A	-0.081	0.19	-9999	-0.4	90	90
USF1	-0.016	0.12	-9999	-0.32	74	74
RAB5/GDP/GDI1	-0.033	0.079	-9999	-0.22	72	72
NOS2	-0.021	0.15	-9999	-0.7	8	8
DDIT3	-0.016	0.12	-9999	-0.32	74	74
RAB5A	0.011	0	-9999	-10000	0	0
HSPB1	-0.006	0.1	-9999	-0.25	72	72
p38alpha-beta/HBP1	-0.012	0.12	-9999	-0.3	72	72
CREB1	-0.018	0.14	-9999	-0.34	74	74
RAB5/GDP	0.008	0	-9999	-10000	0	0
EIF4E	-0.007	0.1	-9999	-0.26	72	72
RPS6KA4	-0.016	0.12	-9999	-0.32	74	74
PLA2G4A	-0.018	0.13	-9999	-0.3	73	73
GDI1	-0.016	0.12	-9999	-0.32	74	74
TP53	-0.024	0.15	-9999	-0.39	74	74
RPS6KA5	-0.019	0.13	-9999	-0.32	79	79
ESR1	-0.051	0.18	-9999	-0.36	112	112
HBP1	0.011	0	-9999	-10000	0	0
MEF2C	-0.052	0.17	-9999	-0.38	83	83
MEF2A	-0.02	0.13	-9999	-0.33	78	78
EIF4EBP1	-0.017	0.14	-9999	-0.34	74	74
KRT19	-0.02	0.13	-9999	-0.32	78	78
ELK4	-0.016	0.12	-9999	-0.32	74	74
ATF6	-0.016	0.12	-9999	-0.32	74	74
ATF1	-0.018	0.14	-9999	-0.34	74	74
p38alpha-beta/MAPKAPK2	-0.012	0.12	-9999	-0.3	72	72
p38alpha-beta/MAPKAPK3	-0.012	0.12	-9999	-0.3	72	72

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.13	0.13	-9999	-0.23	301	301
fibroblast growth factor receptor signaling pathway	-0.13	0.12	-9999	-0.23	301	301
LAMA1	-0.11	0.14	-9999	-0.27	223	223
PRNP	-0.052	0.15	-9999	-0.42	75	75
GPC1/SLIT2	-0.03	0.11	-9999	-0.29	77	77
SMAD2	0.02	0.036	-9999	-0.2	13	13
GPC1/PrPc/Cu2+	-0.023	0.09	-9999	-0.24	75	75
GPC1/Laminin alpha1	-0.067	0.095	-9999	-0.18	223	223
TDGF1	-0.019	0.1	-9999	-0.36	41	41
CRIPTO/GPC1	-0.005	0.072	-9999	-0.24	41	41
APP/GPC1	0.016	0	-9999	-10000	0	0
mol:NO	0	0	-9999	-10000	0	0
YES1	0.004	0.06	-9999	-0.23	25	25
FLT1	0.01	0.019	-9999	-0.42	1	1
GPC1/TGFB/TGFBR1/TGFBR2	0.015	0.04	-9999	-0.23	13	13
SERPINC1	0.007	0.022	-9999	-0.27	3	3
FYN	0.004	0.06	-9999	-0.23	25	25
FGR	-0.003	0.072	-9999	-0.24	37	37
positive regulation of MAPKKK cascade	0.014	0.073	-9999	-0.28	26	26
SLIT2	-0.054	0.15	-9999	-0.42	77	77
GPC1/NRG	0.006	0.051	-9999	-0.28	16	16
NRG1	-0.003	0.073	-9999	-0.41	16	16
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.021	0.011	-9999	-0.23	1	1
LYN	0.004	0.06	-9999	-0.23	25	25
mol:Spermine	0.009	0	-9999	-10000	0	0
cell growth	-0.13	0.12	-9999	-0.23	301	301
BMP signaling pathway	-0.011	0	-9999	-10000	0	0
SRC	0.004	0.06	-9999	-0.23	25	25
TGFBR1	0.011	0	-9999	-10000	0	0
mol:Cu2+	0	0	-9999	-10000	0	0
PLA2G2A	-0.083	0.17	-9999	-0.41	112	112
GPC1	0.011	0	-9999	-10000	0	0
TGFBR1 (dimer)	0.011	0	-9999	-10000	0	0
VEGFA	0.011	0	-9999	-10000	0	0
BLK	-0.01	0.072	-9999	-0.24	26	26
HCK	0.004	0.06	-9999	-0.23	25	25
FGF2	-0.24	0.21	-9999	-0.42	301	301
FGFR1	0.01	0.019	-9999	-0.42	1	1
VEGFR1 homodimer	0.01	0.019	-9999	-0.42	1	1
TGFBR2	0	0.067	-9999	-0.42	13	13
cell death	0.016	0	-9999	-10000	0	0
ATIII/GPC1	0.013	0.015	-9999	-0.18	3	3
PLA2G2A/GPC1	-0.05	0.12	-9999	-0.28	112	112
LCK	0.002	0.063	-9999	-0.24	26	26
neuron differentiation	0.006	0.051	-9999	-0.28	16	16
PrPc/Cu2+	-0.036	0.11	-9999	-0.29	75	75
APP	0.011	0	-9999	-10000	0	0
TGFBR2 (dimer)	0	0.067	-9999	-0.42	13	13

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.008	0.008	-9999	-0.18	1	1
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	0.01	0.022	-9999	-0.18	7	7
STXBP1	-0.017	0.1	-9999	-0.42	33	33
ACh/CHRNA1	-0.092	0.09	-9999	-0.19	200	200
RAB3GAP2/RIMS1/UNC13B	0.017	0.018	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
UniProt:P30996	0	0	-9999	-10000	0	0
UniProt:Q60393	0	0	-9999	-10000	0	0
CST086	0	0	-9999	-10000	0	0
RIMS1	0.003	0.033	-9999	-0.27	7	7
mol:ACh	-0.047	0.057	-9999	-0.11	244	244
RAB3GAP2	0.011	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.066	0.076	-9999	-0.26	34	34
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.092	0.09	-9999	-0.19	200	200
UNC13B	0.011	0	-9999	-10000	0	0
CHRNA1	-0.099	0.14	-9999	-0.27	199	199
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.081	0.12	-9999	-0.31	106	106
SNAP25	-0.12	0.13	-9999	-0.25	244	244
VAMP2	0.005	0.01	-9999	-0.23	1	1
SYT1	-0.077	0.17	-9999	-0.42	105	105
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.002	0.062	-9999	-0.24	34	34
STX1A/SNAP25 fragment 1/VAMP2	-0.066	0.076	-9999	-0.26	34	34

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.008	0.033	-9999	-0.42	3	3
LAT2	-0.085	0.13	-9999	-0.24	196	196
AP1	-0.15	0.15	-9999	-0.36	122	122
mol:PIP3	-0.09	0.16	-9999	-0.41	44	44
IKBKB	-0.049	0.1	-9999	-0.23	59	59
AKT1	-0.045	0.11	-9999	-0.29	46	46
IKBKG	-0.049	0.1	-9999	-0.23	59	59
MS4A2	-0.15	0.2	-9999	-0.41	196	196
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.009	0.019	-9999	-0.42	1	1
MAP3K1	-0.061	0.12	-9999	-0.31	44	44
mol:Ca2+	-0.068	0.13	-9999	-0.31	44	44
LYN	0.009	0.003	-9999	-10000	0	0
CBLB	-0.084	0.13	-9999	-0.32	57	57
SHC1	0.011	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.047	0.11	-9999	-0.22	146	146
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0.01	0.019	-9999	-0.42	1	1
PLD2	-0.073	0.12	-9999	-0.27	84	84
PTPN13	-0.11	0.16	-9999	-0.39	67	67
PTPN11	0.009	0.005	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.046	0.11	-9999	-0.27	46	46
SYK	0.009	0.013	-9999	-0.27	1	1
GRB2	0.01	0.001	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.12	0.14	-9999	-0.37	58	58
LAT	-0.084	0.13	-9999	-0.23	196	196
PAK2	-0.072	0.14	-9999	-0.35	44	44
NFATC2	-0.086	0.16	-9999	-0.54	51	51
HRAS	-0.083	0.14	-9999	-0.38	44	44
GAB2	0.006	0.042	-9999	-0.42	5	5
PLA2G1B	0.029	0.015	-9999	-10000	0	0
Fc epsilon R1	-0.12	0.14	-9999	-0.26	239	239
Antigen/IgE/Fc epsilon R1	-0.11	0.13	-9999	-0.23	239	239
mol:GDP	-0.092	0.15	-9999	-0.36	59	59
JUN	0.006	0.046	-9999	-0.42	6	6
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.007	0.038	-9999	-0.42	4	4
FOS	-0.13	0.2	-9999	-0.42	174	174
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.094	0.14	-9999	-0.25	197	197
CHUK	-0.049	0.1	-9999	-0.23	59	59
KLRG1	-0.072	0.12	-9999	-0.33	42	42
VAV1	-0.086	0.14	-9999	-0.24	196	196
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.084	0.13	-9999	-0.23	196	196
negative regulation of mast cell degranulation	-0.062	0.11	-9999	-0.31	41	41
BTK	-0.097	0.15	-9999	-0.41	45	45
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.095	0.15	-9999	-0.32	102	102
GAB2/PI3K/SHP2	-0.075	0.095	-9999	-0.31	46	46
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.081	0.13	-9999	-0.41	42	42
RAF1	0.021	0.018	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.085	0.13	-9999	-0.28	88	88
FCER1G	0.017	0.021	-9999	-0.28	2	2
FCER1A	-0.063	0.16	-9999	-0.43	84	84
Antigen/IgE/Fc epsilon R1/Fyn	-0.095	0.12	-9999	-0.29	84	84
MAPK3	0.028	0.015	-9999	-10000	0	0
MAPK1	0.028	0.015	-9999	-10000	0	0
NFKB1	0.01	0.019	-9999	-0.42	1	1
MAPK8	-0.018	0.076	-9999	-0.55	6	6
DUSP1	-0.11	0.19	-9999	-0.42	145	145
NF-kappa-B/RelA	-0.043	0.049	-9999	-0.17	8	8
actin cytoskeleton reorganization	-0.098	0.15	-9999	-0.4	41	41
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.096	0.11	-9999	-0.35	47	47
FER	-0.084	0.13	-9999	-0.23	196	196
RELA	0.011	0	-9999	-10000	0	0
ITK	-0.037	0.064	-9999	-0.38	13	13
SOS1	0.011	0	-9999	-10000	0	0
PLCG1	-0.089	0.15	-9999	-0.4	44	44
cytokine secretion	-0.032	0.036	-9999	-10000	0	0
SPHK1	-0.084	0.13	-9999	-0.36	44	44
PTK2	-0.1	0.15	-9999	-0.41	41	41
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.12	0.14	-9999	-0.39	58	58
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.087	0.16	-9999	-0.41	45	45
MAP2K2	0.025	0.016	-9999	-10000	0	0
MAP2K1	0.025	0.016	-9999	-10000	0	0
MAP2K7	0.011	0	-9999	-10000	0	0
KLRG1/SHP2	-0.068	0.092	-9999	-0.29	41	41
MAP2K4	0.009	0.039	-9999	-0.84	1	1
Fc epsilon R1/FcgammaRIIB	-0.096	0.14	-9999	-0.22	240	240
mol:Choline	-0.072	0.12	-9999	-0.26	84	84
SHC/Grb2/SOS1	-0.084	0.11	-9999	-0.34	41	41
FYN	0.011	0	-9999	-10000	0	0
DOK1	0.011	0	-9999	-10000	0	0
PXN	-0.09	0.14	-9999	-0.38	41	41
HCLS1	-0.084	0.13	-9999	-0.32	58	58
PRKCB	-0.075	0.13	-9999	-0.32	61	61
FCGR2B	0.008	0.035	-9999	-0.38	4	4
IGHE	-0.002	0.004	-9999	-10000	0	0
KLRG1/SHIP	-0.063	0.11	-9999	-0.31	41	41
LCP2	0.01	0.013	-9999	-0.28	1	1
PLA2G4A	-0.094	0.14	-9999	-0.25	201	201
RASA1	0.006	0.042	-9999	-0.42	5	5
mol:Phosphatidic acid	-0.072	0.12	-9999	-0.26	84	84
IKK complex	-0.028	0.081	-9999	-0.17	59	59
WIPF1	0.009	0.027	-9999	-0.42	2	2

×

IGF1 pathway

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
NCK2	0.011	0	-10000	0	-10000	0	0
PTK2	0.011	0	-10000	0	-10000	0	0
CRKL	-0.044	0.12	-10000	0	-0.26	111	111
GRB2/SOS1/SHC	0.022	0	-10000	0	-10000	0	0
HRAS	0.011	0	-10000	0	-10000	0	0
IRS1/Crk	-0.044	0.12	-10000	0	-0.26	111	111
IGF-1R heterotetramer/IGF1/PTP1B	-0.041	0.12	-10000	0	-0.26	111	111
AKT1	-0.024	0.11	-10000	0	-0.34	36	36
BAD	-0.018	0.1	-10000	0	-0.31	36	36
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.044	0.12	-10000	0	-0.26	111	111
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.045	0.12	-10000	0	-0.26	111	111
RAF1	-0.013	0.1	-10000	0	-0.3	36	36
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.035	0.12	-10000	0	-0.24	111	111
YWHAZ	0.011	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.055	0.13	-10000	0	-0.26	130	130
PIK3CA	0.01	0.019	-10000	0	-0.42	1	1
RPS6KB1	-0.024	0.11	-10000	0	-0.34	36	36
GNB2L1	0.011	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.013	0.09	-10000	0	-0.26	36	36
PXN	0.011	0	-10000	0	-10000	0	0
PIK3R1	0.007	0.038	-10000	0	-0.42	4	4
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.016	0	-10000	0	-10000	0	0
HRAS/GTP	-0.048	0.095	-10000	0	-0.33	35	35
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.017	0.095	-10000	0	-0.26	35	35
IGF-1R heterotetramer	-0.021	0.095	-10000	0	-0.47	20	20
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.044	0.12	-10000	0	-0.26	111	111
Crk/p130 Cas/Paxillin	-0.029	0.11	-10000	0	-0.22	111	111
IGF1R	-0.021	0.095	-10000	0	-0.47	20	20
IGF1	-0.082	0.18	-10000	0	-0.44	102	102
IRS2/Crk	-0.063	0.14	-10000	0	-0.25	159	159
PI3K	-0.037	0.12	-10000	0	-0.24	113	113
apoptosis	0.01	0.094	0.27	36	-10000	0	36
HRAS/GDP	0.008	0	-10000	0	-10000	0	0
PRKCD	-0.052	0.16	-10000	0	-0.34	111	111
RAF1/14-3-3 E	-0.005	0.092	-10000	0	-0.26	36	36
BAD/14-3-3	-0.01	0.099	-10000	0	-0.29	36	36
PRKCZ	-0.025	0.11	-10000	0	-0.34	36	36
Crk/p130 Cas/Paxillin/FAK1	-0.04	0.081	-10000	0	-0.28	36	36
PTPN1	0.011	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.06	0.17	-10000	0	-0.36	111	111
BCAR1	0.011	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.026	0.1	-10000	0	-0.21	112	112
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.011	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.044	0.12	-10000	0	-0.26	111	111
GRB10	0.01	0.019	-10000	0	-0.42	1	1
PTPN11	-0.044	0.12	-10000	0	-0.26	111	111
IRS1	-0.05	0.13	-10000	0	-0.28	111	111
IRS2	-0.073	0.15	-10000	0	-0.27	159	159
IGF-1R heterotetramer/IGF1	-0.065	0.15	-10000	0	-0.34	111	111
GRB2	0.011	0	-10000	0	-10000	0	0
PDPK1	-0.031	0.12	-10000	0	-0.23	113	113
YWHAE	0.011	0	-10000	0	-10000	0	0
PRKD1	-0.064	0.17	-10000	0	-0.36	115	115
SHC1	0.011	0	-10000	0	-10000	0	0

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	-0.032	0.13	-10000	0	-0.42	51	51
GNB1/GNG2	-0.046	0.077	-10000	0	-0.19	104	104
AKT1	-0.024	0.1	-10000	0	-0.2	104	104
EGF	-0.002	0.058	-10000	0	-0.29	20	20
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.013	0.059	-10000	0	-0.22	8	8
mol:Ca2+	-0.056	0.15	-10000	0	-0.3	127	127
LYN	0.017	0.05	-10000	0	-10000	0	0
RhoA/GTP	-0.031	0.052	-10000	0	-0.12	111	111
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.056	0.16	-10000	0	-0.34	116	116
GNG2	-0.002	0.071	-10000	0	-0.41	15	15
ARRB2	0.011	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.001	0.074	-10000	0	-0.33	15	15
G beta5/gamma2	-0.06	0.1	-10000	0	-0.26	104	104
PRKCH	-0.064	0.17	-10000	0	-0.35	124	124
DNM1	0.008	0.033	-10000	0	-0.42	3	3
TXA2/TP beta/beta Arrestin3	-0.004	0.017	-10000	0	-0.2	2	2
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	-0.032	0.13	-10000	0	-0.42	50	50
G12 family/GTP	-0.077	0.13	-10000	0	-0.29	124	124
ADRBK1	0.011	0	-10000	0	-10000	0	0
ADRBK2	0.01	0.019	-10000	0	-0.42	1	1
RhoA/GTP/ROCK1	0.011	0.006	-10000	0	-10000	0	0
mol:GDP	0.029	0.098	0.21	70	-10000	0	70
mol:NADP	0.009	0.023	-10000	0	-0.34	2	2
RAB11A	0.011	0	-10000	0	-10000	0	0
PRKG1	-0.19	0.21	-10000	0	-0.42	242	242
mol:IP3	-0.074	0.18	-10000	0	-0.38	127	127
cell morphogenesis	0.011	0.006	-10000	0	-10000	0	0
PLCB2	-0.11	0.24	-10000	0	-0.52	127	127
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	0.015	0.055	-10000	0	-0.23	2	2
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.017	0.05	-10000	0	-10000	0	0
RHOA	0.011	0	-10000	0	-10000	0	0
PTGIR	0.01	0.019	-10000	0	-0.42	1	1
PRKCB1	-0.072	0.18	-10000	0	-0.37	127	127
GNAQ	0.009	0.027	-10000	0	-0.42	2	2
mol:L-citrulline	0.009	0.023	-10000	0	-0.34	2	2
TXA2/TXA2-R family	-0.1	0.24	-10000	0	-0.53	116	116
LCK	0.017	0.051	-10000	0	-0.16	1	1
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.016	0.049	-10000	0	-10000	0	0
TXA2-R family/G12 family/GDP/G beta/gamma	0.015	0.033	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.015	0.048	-10000	0	-10000	0	0
MAPK14	-0.03	0.11	-10000	0	-0.22	114	114
TGM2/GTP	-0.092	0.22	-10000	0	-0.45	127	127
MAPK11	-0.03	0.11	-10000	0	-0.22	114	114
ARHGEF1	-0.024	0.087	-10000	0	-0.17	117	117
GNAI2	0.011	0	-10000	0	-10000	0	0
JNK cascade	-0.069	0.18	-10000	0	-0.38	117	117
RAB11/GDP	0.011	0.001	-10000	0	-10000	0	0
ICAM1	-0.044	0.13	-10000	0	-0.28	112	112
cAMP biosynthetic process	-0.074	0.17	-10000	0	-0.36	127	127
Gq family/GTP/EBP50	-0.002	0.065	-10000	0	-0.17	63	63
actin cytoskeleton reorganization	0.011	0.006	-10000	0	-10000	0	0
SRC	0.017	0.05	-10000	0	-10000	0	0
GNB5	0.011	0	-10000	0	-10000	0	0
GNB1	0.011	0	-10000	0	-10000	0	0
EGF/EGFR	0.028	0.049	-10000	0	-0.2	5	5
VCAM1	-0.053	0.15	-10000	0	-0.32	110	110
TP beta/Gq family/GDP/G beta5/gamma2	0.001	0.074	-10000	0	-0.33	15	15
platelet activation	-0.042	0.15	-10000	0	-0.3	117	117
PGI2/IP	0.007	0.013	-10000	0	-0.29	1	1
PRKACA	-0.006	0.067	-10000	0	-0.21	51	51
Gq family/GDP/G beta5/gamma2	-0.001	0.074	-10000	0	-0.32	15	15
TXA2/TP beta/beta Arrestin2	-0.004	0.034	-10000	0	-0.44	3	3
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0	0.064	-10000	0	-0.19	51	51
mol:DAG	-0.082	0.2	-10000	0	-0.42	124	124
EGFR	-0.001	0.068	-10000	0	-0.41	14	14
TXA2/TP alpha	-0.1	0.24	-10000	0	-0.5	127	127
Gq family/GTP	-0.023	0.068	-10000	0	-0.2	63	63
YES1	0.017	0.05	-10000	0	-10000	0	0
GNAI2/GTP	-0.015	0.045	-10000	0	-10000	0	0
PGD2/DP	-0.022	0.089	-10000	0	-0.29	50	50
SLC9A3R1	0.008	0.028	-10000	0	-0.27	5	5
FYN	0.017	0.05	-10000	0	-10000	0	0
mol:NO	0.009	0.023	-10000	0	-0.34	2	2
GNA15	0.007	0.033	-10000	0	-0.27	7	7
PGK/cGMP	-0.11	0.13	-10000	0	-0.24	243	243
RhoA/GDP	0.011	0.001	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.008	0.095	-10000	0	-0.34	19	19
NOS3	0.009	0.023	-10000	0	-0.34	2	2
RAC1	0.011	0	-10000	0	-10000	0	0
PRKCA	-0.071	0.17	-10000	0	-0.36	124	124
PRKCB	-0.071	0.18	-10000	0	-0.36	124	124
PRKCE	-0.063	0.17	-10000	0	-0.35	116	116
PRKCD	-0.068	0.18	-10000	0	-0.37	117	117
PRKCG	-0.079	0.19	-10000	0	-0.39	124	124
muscle contraction	-0.091	0.23	-10000	0	-0.49	117	117
PRKCZ	-0.056	0.16	-10000	0	-0.34	116	116
ARR3	0.003	0.013	-10000	0	-0.27	1	1
TXA2/TP beta	0.006	0.058	-10000	0	-0.17	26	26
PRKCQ	-0.071	0.18	-10000	0	-0.36	124	124
MAPKKK cascade	-0.091	0.22	-10000	0	-0.46	124	124
SELE	-0.061	0.16	-10000	0	-0.36	112	112
TP beta/GNAI2/GDP/G beta/gamma	0.012	0.067	-10000	0	-0.34	4	4
ROCK1	0.011	0	-10000	0	-10000	0	0
GNA14	-0.034	0.13	-10000	0	-0.42	53	53
chemotaxis	-0.11	0.27	-10000	0	-0.6	111	111
GNA12	0.011	0	-10000	0	-10000	0	0
GNA13	0.011	0	-10000	0	-10000	0	0
GNA11	0.001	0.062	-10000	0	-0.42	11	11
Rac1/GTP	0.006	0.004	-10000	0	-10000	0	0

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.011	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.051	0.094	-10000	0	-0.25	43	43
NT3 (dimer)/TRKC	-0.13	0.18	-10000	0	-0.32	229	229
NT3 (dimer)/TRKB	-0.12	0.17	-10000	0	-0.3	223	223
SHC/Grb2/SOS1/GAB1/PI3K	0.025	0.029	-10000	0	-0.19	9	9
RAPGEF1	0.011	0	-10000	0	-10000	0	0
BDNF	-0.028	0.096	-10000	0	-0.27	69	69
PIK3CA	0.01	0.019	-10000	0	-0.42	1	1
DYNLT1	0.011	0	-10000	0	-10000	0	0
NTRK1	0	0.059	-10000	0	-0.34	14	14
NTRK2	-0.058	0.16	-10000	0	-0.41	84	84
NTRK3	-0.17	0.21	-10000	0	-0.42	220	220
NT-4/5 (dimer)/TRKB	-0.11	0.16	-10000	0	-0.28	213	213
neuron apoptosis	0.14	0.2	0.41	143	-10000	0	143
SHC 2-3/Grb2	-0.15	0.22	-10000	0	-0.44	143	143
SHC1	0.011	0	-10000	0	-10000	0	0
SHC2	-0.19	0.25	-10000	0	-0.54	138	138
SHC3	-0.13	0.17	-10000	0	-0.41	100	100
STAT3 (dimer)	0.017	0	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	-0.086	0.14	-10000	0	-0.26	190	190
RIN/GDP	-0.041	0.082	-10000	0	-0.18	52	52
GIPC1	0.011	0	-10000	0	-10000	0	0
KRAS	0.01	0.012	-10000	0	-0.27	1	1
DNAJA3	-0.12	0.17	0.2	2	-0.29	222	224
RIN/GTP	0.002	0.003	-10000	0	-10000	0	0
CCND1	0.024	0	-10000	0	-10000	0	0
MAGED1	0.009	0.027	-10000	0	-0.42	2	2
PTPN11	0.011	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.001	0.053	-10000	0	-0.3	15	15
SHC/GRB2/SOS1	0.022	0	-10000	0	-10000	0	0
GRB2	0.011	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.044	0.11	-10000	0	-0.24	124	124
TRKA/NEDD4-2	0.008	0.043	-10000	0	-0.23	15	15
ELMO1	0.007	0.038	-10000	0	-0.42	4	4
RhoG/GTP/ELMO1/DOCK1	0.01	0.038	-10000	0	-0.26	9	9
NGF	-0.082	0.18	-10000	0	-0.42	111	111
HRAS	0.011	0	-10000	0	-10000	0	0
DOCK1	0.006	0.046	-10000	0	-0.42	6	6
GAB2	0.006	0.042	-10000	0	-0.42	5	5
RIT2	0.002	0.004	-10000	0	-10000	0	0
RIT1	0.011	0	-10000	0	-10000	0	0
FRS2	0.011	0	-10000	0	-10000	0	0
DNM1	0.008	0.033	-10000	0	-0.42	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.011	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.12	0.16	0.19	2	-0.28	224	226
mol:GDP	-0.061	0.12	-10000	0	-0.26	58	58
NGF (dimer)	-0.082	0.18	-10000	0	-0.42	111	111
RhoG/GDP	0.006	0.026	-10000	0	-0.29	4	4
RIT1/GDP	-0.038	0.083	-10000	0	-0.18	49	49
TIAM1	-0.002	0.072	-10000	0	-0.42	15	15
PIK3R1	0.007	0.038	-10000	0	-0.42	4	4
BDNF (dimer)/TRKB	-0.04	0.1	-10000	0	-0.24	79	79
KIDINS220/CRKL/C3G	0.016	0	-10000	0	-10000	0	0
SHC/RasGAP	0.013	0.03	-10000	0	-0.29	5	5
FRS2 family/SHP2	0.022	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0.026	0.02	-10000	0	-0.2	4	4
RIT1/GTP	0.008	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.023	0.11	-10000	0	-0.41	40	40
RAP1/GDP	-0.047	0.055	-10000	0	-0.16	39	39
KIDINS220/CRKL	0.011	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.028	0.096	-10000	0	-0.27	69	69
ubiquitin-dependent protein catabolic process	-0.04	0.11	-10000	0	-0.24	118	118
Schwann cell development	-0.036	0.031	-10000	0	-10000	0	0
EHD4	0.011	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.027	0	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.029	0.019	-10000	0	-10000	0	0
RAP1B	0.011	0	-10000	0	-10000	0	0
RAP1A	0.011	0	-10000	0	-10000	0	0
CDC42/GTP	-0.12	0.13	-10000	0	-0.34	105	105
ABL1	0.009	0.027	-10000	0	-0.42	2	2
SH2B family/GRB2/SOS1	0.016	0	-10000	0	-10000	0	0
Rap1/GTP	0.012	0.047	-10000	0	-10000	0	0
STAT3	0.017	0	-10000	0	-10000	0	0
axon guidance	-0.12	0.13	-10000	0	-0.33	105	105
MAPK3	-0.034	0.1	-10000	0	-0.21	124	124
MAPK1	-0.034	0.1	-10000	0	-0.21	124	124
CDC42/GDP	-0.038	0.083	-10000	0	-0.18	52	52
NTF3	-0.023	0.11	-10000	0	-0.41	40	40
NTF4	-0.001	0.053	-10000	0	-0.3	15	15
NGF (dimer)/TRKA/FAIM	-0.04	0.11	-10000	0	-0.24	119	119
PI3K	0.013	0.03	-10000	0	-0.29	5	5
FRS3	0.011	0	-10000	0	-10000	0	0
FAIM	0.01	0.019	-10000	0	-0.42	1	1
GAB1	0.007	0.038	-10000	0	-0.42	4	4
RASGRF1	-0.14	0.18	0.2	2	-0.31	244	246
SOS1	0.011	0	-10000	0	-10000	0	0
MCF2L	-0.11	0.15	-10000	0	-0.26	229	229
RGS19	0.011	0	-10000	0	-10000	0	0
CDC42	0.011	0	-10000	0	-10000	0	0
RAS family/GTP	-0.017	0.071	-10000	0	-10000	0	0
Rac1/GDP	-0.038	0.083	-10000	0	-0.18	49	49
NGF (dimer)/TRKA/GRIT	-0.046	0.11	-10000	0	-0.24	123	123
neuron projection morphogenesis	-0.11	0.17	-10000	0	-0.44	65	65
NGF (dimer)/TRKA/NEDD4-2	-0.04	0.11	-10000	0	-0.24	118	118
MAP2K1	0.028	0.019	-10000	0	-0.18	4	4
NGFR	-0.13	0.2	-10000	0	-0.42	168	168
NGF (dimer)/TRKA/GIPC/GAIP	-0.025	0.096	-10000	0	-0.2	120	120
RAS family/GTP/PI3K	0.022	0.022	-10000	0	-0.2	5	5
FRS2 family/SHP2/GRB2/SOS1	0.032	0	-10000	0	-10000	0	0
NRAS	0.011	0	-10000	0	-10000	0	0
GRB2/SOS1	0.016	0	-10000	0	-10000	0	0
PRKCI	0.011	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.011	0	-10000	0	-10000	0	0
PRKCZ	0.009	0.023	-10000	0	-0.34	2	2
MAPKKK cascade	-0.16	0.25	-10000	0	-0.6	119	119
RASA1	0.006	0.042	-10000	0	-0.42	5	5
TRKA/c-Abl	0.007	0.045	-10000	0	-0.24	16	16
SQSTM1	0.011	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.029	0.092	-10000	0	-0.21	79	79
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.021	0.093	-10000	0	-0.19	119	119
MATK	0.003	0.057	-10000	0	-0.4	10	10
NEDD4L	0.01	0.019	-10000	0	-0.42	1	1
RAS family/GDP	-0.043	0.052	-10000	0	-0.16	27	27
NGF (dimer)/TRKA	-0.13	0.17	0.21	2	-0.31	222	224
Rac1/GTP	-0.11	0.12	-10000	0	-0.25	179	179
FRS2 family/SHP2/CRK family	0.032	0	-10000	0	-10000	0	0

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	-0.011	0.033	-9999	-10000	0	0
BIRC5	-0.22	0.11	-9999	-0.27	423	423
NFKBIA	-0.012	0.033	-9999	-10000	0	0
CPEB1	-0.19	0.21	-9999	-0.42	234	234
AKT1	-0.012	0.033	-9999	-10000	0	0
NDEL1	0.011	0	-9999	-10000	0	0
Aurora A/BRCA1	-0.01	0.029	-9999	-10000	0	0
NDEL1/TACC3	-0.029	0.07	-9999	-0.17	79	79
GADD45A	0.011	0	-9999	-10000	0	0
GSK3B	0.004	0.002	-9999	-10000	0	0
PAK1/Aurora A	-0.011	0.033	-9999	-10000	0	0
MDM2	0.011	0	-9999	-10000	0	0
JUB	0.011	0	-9999	-10000	0	0
TPX2	-0.14	0.077	-9999	-0.18	410	410
TP53	0	0.024	-9999	-0.33	1	1
DLG7	-0.02	0.032	-9999	-10000	0	0
AURKAIP1	0.011	0	-9999	-10000	0	0
ARHGEF7	0.011	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	-0.032	0.075	-9999	-0.18	79	79
G2/M transition of mitotic cell cycle	-0.01	0.029	-9999	-10000	0	0
AURKA	-0.025	0.04	-9999	-10000	0	0
AURKB	0.014	0.006	-9999	-10000	0	0
CDC25B	-0.005	0.024	-9999	-10000	0	0
G2/M transition checkpoint	-0.01	0.029	-9999	-10000	0	0
mRNA polyadenylation	-0.12	0.11	-9999	-0.24	234	234
Aurora A/CPEB	-0.12	0.12	-9999	-0.24	234	234
Aurora A/TACC1/TRAP/chTOG	-0.039	0.093	-9999	-0.22	104	104
BRCA1	0.011	0	-9999	-10000	0	0
centrosome duplication	-0.011	0.033	-9999	-10000	0	0
regulation of centrosome cycle	-0.029	0.069	-9999	-0.17	79	79
spindle assembly	-0.039	0.092	-9999	-0.22	104	104
TDRD7	0.011	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.1	0.066	-9999	-0.31	5	5
CENPA	0.024	0.011	-9999	-10000	0	0
Aurora A/PP2A	-0.011	0.033	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.003	0.02	-9999	-10000	0	0
negative regulation of DNA binding	0	0.024	-9999	-0.33	1	1
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0.016	0	-9999	-10000	0	0
RASA1	0.006	0.042	-9999	-0.42	5	5
Ajuba/Aurora A	-0.01	0.029	-9999	-10000	0	0
mitotic prometaphase	-0.023	0.009	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.025	0.04	-9999	-10000	0	0
TACC1	-0.076	0.17	-9999	-0.42	104	104
TACC3	-0.048	0.12	-9999	-0.27	106	106
Aurora A/Antizyme1	-0.003	0.03	-9999	-10000	0	0
Aurora A/RasGAP	-0.014	0.04	-9999	-0.25	5	5
OAZ1	0.011	0	-9999	-10000	0	0
RAN	0.011	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.004	0.002	-9999	-10000	0	0
GIT1	0.011	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0.022	0	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.14	0.077	-9999	-0.18	410	410
PPP2R5D	0.011	0	-9999	-10000	0	0
Aurora A/TPX2	-0.12	0.073	-9999	-0.18	164	164
PAK1	0.011	0	-9999	-10000	0	0
CKAP5	0.011	0	-9999	-10000	0	0

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.041	0.13	-9999	-0.26	113	113
FZD6	0.01	0.019	-9999	-0.42	1	1
WNT6	-0.027	0.11	-9999	-0.35	53	53
WNT4	-0.058	0.16	-9999	-0.42	82	82
FZD3	0.011	0	-9999	-10000	0	0
WNT5A	-0.002	0.072	-9999	-0.42	15	15
WNT11	-0.024	0.1	-9999	-0.3	58	58

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	-0.022	0.1	-10000	0	-0.32	50	50
NFATC2	-0.026	0.18	-10000	0	-0.51	42	42
NFATC3	-0.016	0.087	-10000	0	-0.24	53	53
CD40LG	-0.16	0.34	-10000	0	-0.82	84	84
ITCH	0.027	0.031	-10000	0	-10000	0	0
CBLB	0.027	0.031	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.12	0.25	-10000	0	-0.75	44	44
JUNB	0.006	0.042	-10000	0	-0.42	5	5
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.008	0.029	-10000	0	-0.24	1	1
T cell anergy	0.015	0.052	-10000	0	-0.32	1	1
TLE4	-0.027	0.21	-10000	0	-0.59	54	54
Jun/NFAT1-c-4/p21SNFT	-0.084	0.34	-10000	0	-0.77	88	88
AP-1/NFAT1-c-4	-0.16	0.39	-10000	0	-0.92	87	87
IKZF1	0.005	0.13	-10000	0	-0.41	28	28
T-helper 2 cell differentiation	-0.077	0.22	-10000	0	-0.76	31	31
AP-1/NFAT1	-0.084	0.18	-10000	0	-0.38	97	97
CALM1	0.015	0.021	-10000	0	-10000	0	0
EGR2	-0.11	0.42	-10000	0	-0.91	88	88
EGR3	-0.15	0.48	-10000	0	-1.2	83	83
NFAT1/FOXP3	-0.019	0.15	-10000	0	-0.36	42	42
EGR1	-0.062	0.16	-10000	0	-0.42	86	86
JUN	0.003	0.047	-10000	0	-0.42	6	6
EGR4	0.001	0.045	-10000	0	-0.28	12	12
mol:Ca2+	0.005	0.023	-10000	0	-0.15	1	1
GBP3	0.002	0.14	-10000	0	-0.46	28	28
FOSL1	-0.008	0.07	-10000	0	-0.27	34	34
NFAT1-c-4/MAF/IRF4	-0.12	0.36	-10000	0	-0.83	89	89
DGKA	0.006	0.12	-10000	0	-0.4	25	25
CREM	0.01	0.001	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.1	0.35	-10000	0	-0.81	88	88
CTLA4	-0.029	0.14	-10000	0	-0.37	36	36
NFAT1-c-4 (dimer)/EGR1	-0.13	0.37	-10000	0	-0.86	88	88
NFAT1-c-4 (dimer)/EGR4	-0.094	0.34	-10000	0	-0.8	88	88
FOS	-0.14	0.2	-10000	0	-0.42	174	174
IFNG	-0.058	0.18	-10000	0	-0.63	24	24
T cell activation	-0.084	0.22	-10000	0	-0.66	41	41
MAF	-0.065	0.16	-10000	0	-0.42	91	91
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.078	0.3	0.69	88	-10000	0	88
TNF	-0.12	0.33	-10000	0	-0.77	90	90
FASLG	-0.16	0.48	-10000	0	-1.1	87	87
TBX21	0.009	0.041	-10000	0	-0.36	6	6
BATF3	0.01	0.012	-10000	0	-0.27	1	1
PRKCQ	-0.012	0.1	-10000	0	-0.41	31	31
PTPN1	0.006	0.12	-10000	0	-0.41	21	21
NFAT1-c-4/ICER1	-0.091	0.34	-10000	0	-0.79	88	88
GATA3	-0.002	0.064	-10000	0	-0.3	22	22
T-helper 1 cell differentiation	-0.047	0.18	-10000	0	-0.62	24	24
IL2RA	-0.12	0.24	-10000	0	-0.69	53	53
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	0.006	0.12	-10000	0	-0.41	21	21
E2F1	-0.044	0.12	-10000	0	-0.27	109	109
PPARG	-0.014	0.099	-10000	0	-0.42	29	29
SLC3A2	0.006	0.12	-10000	0	-0.4	23	23
IRF4	-0.002	0.067	-10000	0	-0.34	18	18
PTGS2	-0.18	0.36	-10000	0	-0.85	91	91
CSF2	-0.16	0.33	-10000	0	-0.81	83	83
JunB/Fra1/NFAT1-c-4	-0.087	0.33	-10000	0	-0.76	88	88
IL4	-0.08	0.24	-10000	0	-0.82	29	29
IL5	-0.16	0.33	-10000	0	-0.82	83	83
IL2	-0.085	0.22	-10000	0	-0.67	41	41
IL3	-0.036	0.049	-10000	0	-10000	0	0
RNF128	0.016	0.064	-10000	0	-0.5	1	1
NFATC1	-0.079	0.3	-10000	0	-0.69	88	88
CDK4	0.043	0.18	0.51	36	-10000	0	36
PTPRK	0.004	0.13	-10000	0	-0.41	27	27
IL8	-0.18	0.33	-10000	0	-0.82	84	84
POU2F1	0.011	0	-10000	0	-10000	0	0

×

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

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
MAP4K1	-0.033	0.15	-10000	0	-0.41	51	51
CRKL	-0.038	0.15	-10000	0	-0.44	49	49
HRAS	-0.019	0.14	-10000	0	-0.38	46	46
mol:PIP3	-0.043	0.14	0.19	2	-0.34	77	79
SPRED1	0.011	0	-10000	0	-10000	0	0
SPRED2	0.01	0.019	-10000	0	-0.42	1	1
GAB1	-0.046	0.16	-10000	0	-0.38	77	77
FOXO3	-0.029	0.14	-10000	0	-0.4	48	48
AKT1	-0.037	0.15	-10000	0	-0.43	48	48
BAD	-0.029	0.14	-10000	0	-0.4	48	48
megakaryocyte differentiation	-0.048	0.16	-10000	0	-0.37	79	79
GSK3B	-0.029	0.14	-10000	0	-0.4	48	48
RAF1	-0.008	0.12	-10000	0	-0.31	46	46
SHC1	0.011	0	-10000	0	-10000	0	0
STAT3	-0.044	0.16	-10000	0	-0.37	77	77
STAT1	-0.11	0.35	-10000	0	-0.84	80	80
HRAS/SPRED1	-0.01	0.12	-10000	0	-0.31	46	46
cell proliferation	-0.045	0.16	-10000	0	-0.37	77	77
PIK3CA	0.01	0.019	-10000	0	-0.42	1	1
TEC	0.01	0.012	-10000	0	-0.27	1	1
RPS6KB1	-0.045	0.16	-10000	0	-0.36	86	86
HRAS/SPRED2	-0.01	0.12	-10000	0	-0.31	46	46
LYN/TEC/p62DOK	-0.031	0.15	-10000	0	-0.43	49	49
MAPK3	0.005	0.088	-10000	0	-0.22	46	46
STAP1	-0.047	0.16	-10000	0	-0.37	77	77
GRAP2	-0.006	0.083	-10000	0	-0.42	20	20
JAK2	-0.092	0.3	-10000	0	-0.73	80	80
STAT1 (dimer)	-0.1	0.34	-10000	0	-0.82	80	80
mol:Gleevec	0.001	0.006	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.033	0.15	-10000	0	-0.42	51	51
actin filament polymerization	-0.043	0.16	-10000	0	-0.36	78	78
LYN	0.011	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.058	0.22	-10000	0	-0.51	80	80
PIK3R1	0.007	0.038	-10000	0	-0.42	4	4
CBL/CRKL/GRB2	-0.024	0.14	-10000	0	-0.4	48	48
PI3K	-0.035	0.16	-10000	0	-0.45	49	49
PTEN	0.006	0.046	-10000	0	-0.42	6	6
SCF/KIT/EPO/EPOR	-0.1	0.37	-10000	0	-1.2	45	45
MAPK8	-0.046	0.16	-10000	0	-0.38	77	77
STAT3 (dimer)	-0.043	0.16	-10000	0	-0.36	77	77
positive regulation of transcription	0.007	0.075	-10000	0	-0.18	46	46
mol:GDP	-0.023	0.14	-10000	0	-0.4	46	46
PIK3C2B	-0.044	0.16	-10000	0	-0.37	78	78
CBL/CRKL	-0.03	0.15	-10000	0	-0.41	48	48
FER	-0.044	0.16	-10000	0	-0.37	78	78
SH2B3	-0.045	0.16	-10000	0	-0.38	77	77
PDPK1	-0.034	0.13	-10000	0	-0.38	49	49
SNAI2	-0.07	0.19	-10000	0	-0.42	86	86
positive regulation of cell proliferation	-0.075	0.26	-10000	0	-0.63	80	80
KITLG	-0.035	0.14	-10000	0	-0.43	54	54
cell motility	-0.075	0.26	-10000	0	-0.63	80	80
PTPN6	0.011	0.015	-10000	0	-0.28	1	1
EPOR	-0.012	0.12	-10000	0	-0.45	11	11
STAT5A (dimer)	-0.061	0.22	-10000	0	-0.52	80	80
SOCS1	0.009	0.023	-10000	0	-0.34	2	2
cell migration	0.047	0.16	0.37	79	-10000	0	79
SOS1	0.011	0	-10000	0	-10000	0	0
EPO	0.005	0.036	-10000	0	-0.38	4	4
VAV1	0.007	0.034	-10000	0	-0.3	6	6
GRB10	-0.045	0.16	-10000	0	-0.37	78	78
PTPN11	0.011	0.006	-10000	0	-10000	0	0
SCF/KIT	-0.052	0.17	-10000	0	-0.39	81	81
GO:0007205	0.001	0.008	-10000	0	-10000	0	0
MAP2K1	0.001	0.096	-10000	0	-0.24	46	46
CBL	0.011	0	-10000	0	-10000	0	0
KIT	-0.084	0.35	-10000	0	-1.3	39	39
MAP2K2	0.001	0.096	-10000	0	-0.24	46	46
SHC/Grb2/SOS1	-0.031	0.15	-10000	0	-0.43	48	48
STAT5A	-0.063	0.23	-10000	0	-0.54	80	80
GRB2	0.011	0	-10000	0	-10000	0	0
response to radiation	-0.068	0.18	-10000	0	-0.41	86	86
SHC/GRAP2	0.004	0.058	-10000	0	-0.29	20	20
PTPRO	-0.05	0.16	-10000	0	-0.38	79	79
SH2B2	-0.044	0.16	-10000	0	-0.37	78	78
DOK1	0.011	0	-10000	0	-10000	0	0
MATK	-0.048	0.16	-10000	0	-0.38	79	79
CREBBP	0.016	0.041	-10000	0	-0.45	1	1
BCL2	-0.1	0.38	-10000	0	-1.3	48	48

×

PLK1 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0.025	0.018	-9999	-10000	0	0
BUB1B	-0.036	0.034	-9999	-10000	0	0
PLK1	-0.004	0.016	-9999	-10000	0	0
PLK1S1	0.001	0.015	-9999	-0.25	1	1
KIF2A	0.003	0.014	-9999	-10000	0	0
regulation of mitotic centrosome separation	-0.004	0.016	-9999	-10000	0	0
GOLGA2	0.011	0	-9999	-10000	0	0
Hec1/SPC24	-0.072	0.079	-9999	-0.15	152	152
WEE1	0	0.016	-9999	-10000	0	0
cytokinesis	-0.044	0.033	-9999	-0.19	13	13
PP2A-alpha B56	0.055	0.015	-9999	-10000	0	0
AURKA	0.005	0.006	-9999	-10000	0	0
PICH/PLK1	-0.064	0.088	-9999	-0.22	76	76
CENPE	-0.033	0.068	-9999	-0.14	137	137
RhoA/GTP	0.008	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.003	0.014	-9999	-10000	0	0
PPP2CA	0.011	0	-9999	-10000	0	0
FZR1	0.011	0	-9999	-10000	0	0
TPX2	0.004	0.007	-9999	-10000	0	0
PAK1	0.01	0.001	-9999	-10000	0	0
SPC24	-0.15	0.14	-9999	-0.27	298	298
FBXW11	0.011	0	-9999	-10000	0	0
CLSPN	0.004	0.008	-9999	-10000	0	0
GORASP1	0.011	0	-9999	-10000	0	0
metaphase	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NLP	-0.003	0.01	-9999	-10000	0	0
G2 phase of mitotic cell cycle	-0.001	0.001	-9999	-10000	0	0
STAG2	0.011	0	-9999	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.012	0.006	-9999	-10000	0	0
spindle elongation	-0.004	0.016	-9999	-10000	0	0
ODF2	0.01	0.001	-9999	-10000	0	0
BUB1	0.045	0.025	-9999	-10000	0	0
TPT1	0.002	0.01	-9999	-10000	0	0
CDC25C	0.009	0.008	-9999	-10000	0	0
CDC25B	0.011	0	-9999	-10000	0	0
SGOL1	-0.025	0.018	-9999	-10000	0	0
RHOA	0.011	0	-9999	-10000	0	0
CCNB1/CDK1	-0.011	0.035	-9999	-10000	0	0
CDC14B	0.008	0.014	-9999	-0.3	1	1
CDC20	-0.25	0.082	-9999	-0.27	465	465
PLK1/PBIP1	-0.016	0.044	-9999	-0.13	60	60
mitosis	-0.005	0.007	-9999	-0.015	164	164
FBXO5	0.001	0.015	-9999	-10000	0	0
CDC2	-0.001	0.002	-9999	-10000	0	0
NDC80	-0.004	0.062	-9999	-0.27	26	26
metaphase plate congression	0	0.011	-9999	-10000	0	0
ERCC6L	-0.056	0.081	-9999	-0.19	76	76
NLP/gamma Tubulin	0	0.009	-9999	-10000	0	0
microtubule cytoskeleton organization	0.002	0.01	-9999	-10000	0	0
G2/M transition DNA damage checkpoint	-0.001	0.001	-9999	-10000	0	0
PPP1R12A	0.009	0.027	-9999	-0.42	2	2
interphase	-0.001	0.001	-9999	-10000	0	0
PLK1/PRC1-2	-0.11	0.052	-9999	-0.15	163	163
GRASP65/GM130/RAB1/GTP/PLK1	0.015	0.012	-9999	-10000	0	0
RAB1A	0.011	0	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
Aurora A/BORA	0.001	0.016	-9999	-10000	0	0
mitotic prometaphase	-0.002	0.001	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.004	0.013	-9999	-10000	0	0
microtubule-based process	-0.12	0.044	-9999	-0.13	469	469
Golgi organization	-0.004	0.016	-9999	-10000	0	0
Cohesin/SA2	-0.005	0.008	-9999	-10000	0	0
PPP1CB/MYPT1	0.014	0.019	-9999	-0.29	2	2
KIF20A	-0.25	0.079	-9999	-0.27	469	469
APC/C/CDC20	-0.12	0.047	-9999	-0.14	465	465
PPP2R1A	0.011	0	-9999	-10000	0	0
chromosome segregation	-0.019	0.042	-9999	-0.13	60	60
PRC1	-0.001	0.056	-9999	-0.27	21	21
ECT2	-0.005	0.037	-9999	-0.14	28	28
C13orf34	0.002	0.014	-9999	-10000	0	0
NUDC	0	0.011	-9999	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.035	0.034	-9999	-10000	0	0
spindle assembly	-0.001	0.014	-9999	-10000	0	0
spindle stabilization	0.001	0.015	-9999	-0.25	1	1
APC/C/HCDH1	0.014	0.011	-9999	-0.24	1	1
MKLP2/PLK1	-0.12	0.044	-9999	-0.14	469	469
CCNB1	-0.042	0.11	-9999	-0.27	96	96
PPP1CB	0.01	0.001	-9999	-10000	0	0
BTRC	0.011	0	-9999	-10000	0	0
ROCK2	-0.003	0.064	-9999	-0.4	13	13
TUBG1	0.002	0.01	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.017	0.031	-9999	-10000	0	0
MLF1IP	-0.019	0.061	-9999	-0.19	60	60
INCENP	0.01	0.001	-9999	-10000	0	0

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.018	0.08	-9999	-0.24	58	58
EFNA5	-0.002	0.072	-9999	-0.4	16	16
FYN	-0.01	0.072	-9999	-0.21	57	57
neuron projection morphogenesis	-0.018	0.08	-9999	-0.24	58	58
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.018	0.08	-9999	-0.24	58	58
EPHA5	-0.031	0.12	-9999	-0.42	43	43

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.03	0.1	0.28	75	-10000	0	75
KIRREL	-0.044	0.14	-10000	0	-0.42	65	65
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.03	0.1	-10000	0	-0.28	75	75
PLCG1	0.011	0	-10000	0	-10000	0	0
ARRB2	0.011	0	-10000	0	-10000	0	0
WASL	0.011	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.009	0.077	-10000	0	-0.21	65	65
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.006	0.079	-10000	0	-0.21	65	65
FYN	-0.014	0.073	-10000	0	-0.2	65	65
mol:Ca2+	-0.015	0.075	-10000	0	-0.2	65	65
mol:DAG	-0.01	0.076	-10000	0	-0.2	65	65
NPHS2	-0.002	0.015	-10000	0	-10000	0	0
mol:IP3	-0.01	0.076	-10000	0	-0.2	65	65
regulation of endocytosis	-0.003	0.07	-10000	0	-0.18	65	65
Nephrin/NEPH1/podocin/Cholesterol	-0.018	0.076	-10000	0	-0.21	65	65
establishment of cell polarity	-0.03	0.1	-10000	0	-0.28	75	75
Nephrin/NEPH1/podocin/NCK1-2	0	0.073	-10000	0	-0.36	3	3
Nephrin/NEPH1/beta Arrestin2	-0.002	0.07	-10000	0	-0.18	65	65
NPHS1	-0.003	0.042	-10000	0	-0.27	11	11
Nephrin/NEPH1/podocin	-0.01	0.074	-10000	0	-0.2	65	65
TJP1	0.01	0.019	-10000	0	-0.42	1	1
NCK1	0.009	0.027	-10000	0	-0.42	2	2
NCK2	0.011	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.009	0.077	-10000	0	-0.21	65	65
CD2AP	0.011	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.009	0.077	-10000	0	-0.21	65	65
GRB2	0.011	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.027	0.097	-10000	0	-0.22	92	92
cytoskeleton organization	-0.003	0.083	-10000	0	-0.22	65	65
Nephrin/NEPH1	-0.018	0.072	-10000	0	-0.2	65	65
Nephrin/NEPH1/ZO-1	-0.015	0.084	-10000	0	-0.23	65	65

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.035	0.094	-9999	-0.28	14	14
NF kappa B1 p50/RelA/I kappa B alpha	-0.01	0.087	-9999	-0.25	11	11
alphaV/beta3 Integrin/Osteopontin/Src	-0.027	0.082	-9999	-0.16	134	134
AP1	-0.085	0.15	-9999	-0.38	68	68
ILK	-0.045	0.1	-9999	-0.29	16	16
bone resorption	-0.026	0.099	-9999	-0.3	26	26
PTK2B	0.011	0	-9999	-10000	0	0
PYK2/p130Cas	0.011	0.1	-9999	-0.28	13	13
ITGAV	0.014	0.001	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.002	0.064	-9999	-0.29	24	24
alphaV/beta3 Integrin/Osteopontin	-0.059	0.11	-9999	-0.23	106	106
MAP3K1	-0.046	0.1	-9999	-0.2	106	106
JUN	0.006	0.046	-9999	-0.42	6	6
MAPK3	-0.032	0.095	-9999	-0.29	12	12
MAPK1	-0.032	0.095	-9999	-0.29	12	12
Rac1/GDP	0.008	0	-9999	-10000	0	0
NFKB1	0.01	0.019	-9999	-0.42	1	1
MAPK8	-0.038	0.099	-9999	-0.29	20	20
ITGB3	-0.074	0.17	-9999	-0.41	107	107
NFKBIA	-0.022	0.093	-9999	-0.28	11	11
FOS	-0.13	0.2	-9999	-0.42	174	174
CD44	0.001	0.062	-9999	-0.42	11	11
CHUK	0.011	0	-9999	-10000	0	0
PLAU	-0.019	0.09	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.041	0.056	-9999	-0.25	3	3
BCAR1	0.011	0	-9999	-10000	0	0
RELA	0.011	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.04	0.12	-9999	-0.28	106	106
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.047	0.1	-9999	-0.2	106	106
VAV3	-0.07	0.11	-9999	-0.26	70	70
MAP3K14	-0.044	0.1	-9999	-0.2	106	106
ROCK2	0	0.067	-9999	-0.42	13	13
SPP1	-0.059	0.12	-9999	-0.27	134	134
RAC1	0.011	0	-9999	-10000	0	0
Rac1/GTP	-0.059	0.099	-9999	-0.23	69	69
MMP2	-0.077	0.15	-9999	-0.37	72	72

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	0.005	0.067	-10000	0	-0.25	29	29
alphaM/beta2 Integrin/GPIbA	0.016	0.038	-10000	0	-0.25	7	7
alphaM/beta2 Integrin/proMMP-9	-0.051	0.084	-10000	0	-0.18	47	47
PLAUR	0.008	0.025	-10000	0	-0.27	4	4
HMGB1	0.01	0.01	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Talin	0.018	0.03	-10000	0	-0.22	5	5
AGER	0.009	0.021	-10000	0	-0.41	1	1
RAP1A	0.011	0	-10000	0	-10000	0	0
SELPLG	0.011	0	-10000	0	-10000	0	0
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	0.02	0.054	-10000	0	-0.21	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	-0.11	0.14	-10000	0	-0.27	222	222
CYR61	-0.033	0.13	-10000	0	-0.42	52	52
TLN1	0.011	0	-10000	0	-10000	0	0
Rap1/GTP	-0.027	0.063	-10000	0	-0.26	13	13
RHOA	0.011	0	-10000	0	-10000	0	0
P-selectin oligomer	-0.17	0.21	-10000	0	-0.42	222	222
MYH2	-0.027	0.11	-10000	0	-0.27	45	45
MST1R	-0.03	0.1	-10000	0	-0.27	73	73
leukocyte activation during inflammatory response	-0.008	0.036	-10000	0	-0.22	7	7
APOB	0.005	0.022	-10000	0	-0.27	3	3
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	-0.011	0.094	-10000	0	-0.42	26	26
JAM3	-0.1	0.19	-10000	0	-0.42	134	134
GP1BA	0.007	0.029	-10000	0	-0.37	3	3
alphaM/beta2 Integrin/CTGF	0.009	0.055	-10000	0	-0.23	23	23
alphaM/beta2 Integrin	-0.02	0.085	-10000	0	-0.21	49	49
JAM3 homodimer	-0.1	0.19	-10000	0	-0.42	134	134
ICAM2	0.011	0	-10000	0	-10000	0	0
ICAM1	0.009	0.022	-10000	0	-0.27	3	3
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.02	0.085	-10000	0	-0.21	49	49
cell adhesion	0.014	0.038	-10000	0	-0.25	7	7
NFKB1	0.021	0.083	-10000	0	-0.3	21	21
THY1	0.011	0	-10000	0	-10000	0	0
RhoA/GDP	0.008	0	-10000	0	-10000	0	0
Lipoprotein(a)	0.002	0.034	-10000	0	-0.15	23	23
alphaM/beta2 Integrin/LRP/tPA	-0.002	0.081	-10000	0	-0.22	58	58
IL6	0.011	0.14	-10000	0	-0.63	20	20
ITGB2	0.007	0.027	-10000	0	-0.27	4	4
elevation of cytosolic calcium ion concentration	0.021	0.031	-10000	0	-0.21	4	4
alphaM/beta2 Integrin/JAM2/JAM3	-0.11	0.17	-10000	0	-0.29	228	228
JAM2	-0.14	0.2	-10000	0	-0.42	176	176
alphaM/beta2 Integrin/ICAM1	0.006	0.059	-10000	0	-0.24	8	8
alphaM/beta2 Integrin/uPA/Plg	-0.011	0.086	-10000	0	-0.21	74	74
RhoA/GTP	-0.03	0.11	-10000	0	-0.25	74	74
positive regulation of phagocytosis	-0.017	0.052	-10000	0	-0.21	17	17
Ron/MSP	-0.015	0.072	-10000	0	-0.18	82	82
alphaM/beta2 Integrin/uPAR/uPA	0.022	0.032	-10000	0	-0.21	4	4
alphaM/beta2 Integrin/uPAR	0.016	0.033	-10000	0	-0.21	6	6
PLAU	0.01	0.018	-10000	0	-0.27	2	2
PLAT	-0.035	0.13	-10000	0	-0.42	55	55
actin filament polymerization	-0.026	0.1	-10000	0	-0.26	45	45
MST1	0.005	0.039	-10000	0	-0.27	10	10
alphaM/beta2 Integrin/lipoprotein(a)	0.012	0.042	-10000	0	-0.22	7	7
TNF	0.018	0.096	-10000	0	-0.73	2	2
RAP1B	0.011	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPA	0.017	0.032	-10000	0	-0.21	6	6
fibrinolysis	-0.012	0.086	-10000	0	-0.21	74	74
HCK	0.01	0.012	-10000	0	-0.27	1	1
dendritic cell antigen processing and presentation	-0.02	0.085	-10000	0	-0.21	49	49
VTN	-0.053	0.15	-10000	0	-0.41	76	76
alphaM/beta2 Integrin/CYR61	-0.008	0.084	-10000	0	-0.24	55	55
LPA	-0.004	0.056	-10000	0	-0.27	21	21
LRP1	0.009	0.027	-10000	0	-0.42	2	2
cell migration	-0.05	0.088	-10000	0	-0.24	37	37
FN1	0.006	0.042	-10000	0	-0.42	5	5
alphaM/beta2 Integrin/Thy1	0.018	0.03	-10000	0	-0.22	5	5
MPO	0.006	0.033	-10000	0	-0.27	7	7
KNG1	-0.008	0.06	-10000	0	-0.27	25	25
RAP1/GDP	0.014	0	-10000	0	-10000	0	0
ROCK1	-0.023	0.11	-10000	0	-0.26	51	51
ELA2	0	0	-10000	0	-10000	0	0
PLG	-0.053	0.15	-10000	0	-0.41	76	76
CTGF	-0.004	0.079	-10000	0	-0.42	18	18
alphaM/beta2 Integrin/Hck	0.017	0.033	-10000	0	-0.25	5	5
ITGAM	0.006	0.038	-10000	0	-0.35	5	5
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.076	0.12	-10000	0	-0.21	224	224
HP	-0.087	0.15	-10000	0	-0.31	155	155
leukocyte adhesion	-0.11	0.13	0.16	1	-0.33	106	107
SELP	-0.17	0.21	-10000	0	-0.42	222	222

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.072	0.24	-10000	0	-0.63	38	38
PCK1	-0.1	0.33	-10000	0	-1.2	36	36
HNF4A	-0.12	0.32	-10000	0	-0.79	70	70
KCNJ11	-0.06	0.25	-10000	0	-0.68	27	27
AKT1	-0.033	0.14	-10000	0	-0.34	20	20
response to starvation	-0.009	0.032	-10000	0	-0.15	1	1
DLK1	-0.12	0.33	-10000	0	-0.77	75	75
NKX2-1	-0.018	0.14	-10000	0	-0.43	2	2
ACADM	-0.076	0.25	-10000	0	-0.64	43	43
TAT	-0.086	0.19	-10000	0	-0.59	25	25
CEBPB	0.012	0.002	-10000	0	-10000	0	0
CEBPA	0.01	0.035	-10000	0	-0.38	4	4
TTR	-0.004	0.12	-10000	0	-0.64	3	3
PKLR	-0.078	0.24	-10000	0	-0.63	39	39
APOA1	-0.17	0.44	-10000	0	-1.1	71	71
CPT1C	-0.077	0.26	-10000	0	-0.68	40	40
ALAS1	-0.029	0.16	-10000	0	-10000	0	0
TFRC	-0.029	0.18	-10000	0	-0.54	5	5
FOXF1	0.006	0.047	-10000	0	-0.41	6	6
NF1	0.014	0.033	-10000	0	-0.41	3	3
HNF1A (dimer)	-0.005	0.068	-10000	0	-0.28	29	29
CPT1A	-0.072	0.24	-10000	0	-0.62	40	40
HMGCS1	-0.072	0.24	-10000	0	-0.62	41	41
NR3C1	-0.084	0.17	-10000	0	-0.39	114	114
CPT1B	-0.074	0.24	-10000	0	-0.62	41	41
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.009	0.01	-10000	0	-10000	0	0
GCK	-0.13	0.33	-10000	0	-0.76	86	86
CREB1	0.003	0.045	-10000	0	-0.19	12	12
IGFBP1	-0.22	0.45	-10000	0	-1.1	88	88
PDX1	-0.03	0.14	-10000	0	-10000	0	0
UCP2	-0.073	0.24	-10000	0	-0.62	41	41
ALDOB	-0.061	0.25	-10000	0	-0.66	29	29
AFP	-0.028	0.046	-10000	0	-0.33	2	2
BDH1	-0.072	0.24	-10000	0	-0.62	40	40
HADH	-0.06	0.25	-10000	0	-0.65	31	31
F2	-0.11	0.3	-10000	0	-0.78	46	46
HNF1A	-0.005	0.068	-10000	0	-0.28	29	29
G6PC	0.012	0.062	-10000	0	-10000	0	0
SLC2A2	-0.036	0.17	-10000	0	-10000	0	0
INS	0.016	0.06	0.18	41	-10000	0	41
FOXA1	-0.16	0.14	-10000	0	-0.26	328	328
FOXA3	-0.042	0.13	-10000	0	-0.27	112	112
FOXA2	-0.074	0.29	-10000	0	-0.69	44	44
ABCC8	-0.14	0.37	-10000	0	-0.81	96	96
ALB	-0.027	0.064	-10000	0	-1.1	1	1

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.037	0.11	-9999	-0.22	112	112
SMAD6-7/SMURF1	0.021	0.016	-9999	-0.23	2	2
NOG	-0.021	0.089	-9999	-0.27	57	57
SMAD9	-0.056	0.17	-9999	-0.51	54	54
SMAD4	0.01	0.019	-9999	-0.42	1	1
SMAD5	-0.016	0.091	-9999	-0.3	24	24
BMP7/USAG1	-0.048	0.11	-9999	-0.22	138	138
SMAD5/SKI	-0.01	0.087	-9999	-0.29	23	23
SMAD1	0.032	0.015	-9999	-10000	0	0
BMP2	-0.022	0.11	-9999	-0.42	39	39
SMAD1/SMAD1/SMAD4	-0.001	0.011	-9999	-10000	0	0
BMPR1A	0.011	0	-9999	-10000	0	0
BMPR1B	-0.014	0.099	-9999	-0.41	30	30
BMPR1A-1B/BAMBI	-0.003	0.079	-9999	-0.26	41	41
AHSG	0.003	0.033	-9999	-0.27	7	7
CER1	0.004	0.005	-9999	-10000	0	0
BMP2-4/CER1	-0.015	0.087	-9999	-0.25	56	56
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.033	0.12	-9999	-0.34	32	32
BMP2-4 (homodimer)	-0.022	0.1	-9999	-0.28	65	65
RGMB	0.01	0.019	-9999	-0.42	1	1
BMP6/BMPR2/BMPR1A-1B	0.007	0.066	-9999	-0.21	43	43
RGMA	-0.078	0.17	-9999	-0.42	106	106
SMURF1	0.011	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.037	0.11	-9999	-0.29	47	47
BMP2-4/USAG1	-0.035	0.11	-9999	-0.27	71	71
SMAD6/SMURF1/SMAD5	-0.01	0.087	-9999	-0.29	23	23
SOSTDC1	-0.032	0.11	-9999	-0.32	66	66
BMP7/BMPR2/BMPR1A-1B	-0.013	0.085	-9999	-0.24	46	46
SKI	0.011	0	-9999	-10000	0	0
BMP6 (homodimer)	-0.002	0.072	-9999	-0.42	15	15
HFE2	0.004	0.013	-9999	-0.27	1	1
ZFYVE16	0.011	0	-9999	-10000	0	0
MAP3K7	0.011	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.053	0.14	-9999	-0.27	126	126
SMAD5/SMAD5/SMAD4	-0.01	0.089	-9999	-0.3	23	23
MAPK1	0.011	0	-9999	-10000	0	0
TAK1/TAB family	-0.047	0.082	-9999	-0.3	30	30
BMP7 (homodimer)	-0.042	0.12	-9999	-0.3	85	85
NUP214	0.011	0	-9999	-10000	0	0
BMP6/FETUA	0.002	0.055	-9999	-0.25	22	22
SMAD1/SKI	0.036	0.014	-9999	-10000	0	0
SMAD6	0.01	0.019	-9999	-0.42	1	1
CTDSP2	0.011	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.015	0.088	-9999	-0.25	56	56
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.1	0.19	-9999	-0.42	133	133
BMPR2 (homodimer)	0.011	0	-9999	-10000	0	0
GADD34/PP1CA	0.022	0	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.002	0.07	-9999	-0.28	30	30
CHRDL1	-0.29	0.19	-9999	-0.42	360	360
ENDOFIN/SMAD1	0.036	0.014	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	0	0.011	-9999	-10000	0	0
SMAD6/SMURF1	0.011	0	-9999	-10000	0	0
BAMBI	-0.007	0.081	-9999	-0.37	24	24
SMURF2	0.011	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.19	0.14	-9999	-0.26	373	373
BMP2-4/GREM1	-0.075	0.14	-9999	-0.27	168	168
SMAD7	0.01	0.019	-9999	-0.42	1	1
SMAD8A/SMAD8A/SMAD4	-0.047	0.16	-9999	-0.47	55	55
SMAD1/SMAD6	0.036	0.014	-9999	-10000	0	0
TAK1/SMAD6	0.016	0	-9999	-10000	0	0
BMP7	-0.042	0.12	-9999	-0.3	85	85
BMP6	-0.002	0.072	-9999	-0.42	15	15
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.033	0.11	-9999	-0.31	35	35
PPM1A	0.011	0	-9999	-10000	0	0
SMAD1/SMURF2	0.036	0.014	-9999	-10000	0	0
SMAD7/SMURF1	0.015	0.013	-9999	-0.29	1	1
CTDSPL	0.011	0	-9999	-10000	0	0
PPP1CA	0.011	0	-9999	-10000	0	0
XIAP	0.011	0	-9999	-10000	0	0
CTDSP1	0.011	0	-9999	-10000	0	0
PPP1R15A	0.011	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.074	0.16	-9999	-0.39	65	65
CHRD	-0.064	0.16	-9999	-0.42	89	89
BMPR2	0.011	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.045	0.12	-9999	-0.23	114	114
BMP4	-0.012	0.09	-9999	-0.37	30	30
FST	-0.051	0.15	-9999	-0.41	74	74
BMP2-4/NOG	-0.028	0.099	-9999	-0.26	59	59
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.006	0.08	-9999	-0.22	46	46

×

TCGA08_retinoblastoma

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
CDKN2B	0.006	0.024	-10000	0	-0.28	2	2
CDKN2C	0.02	0.054	-10000	0	-0.38	8	8
CDKN2A	-0.12	0.15	-10000	0	-0.28	224	224
CCND2	-0.003	0.045	0.17	4	-0.11	40	44
RB1	0.002	0.04	0.13	2	-0.18	6	8
CDK4	0.015	0.029	0.19	6	-10000	0	6
CDK6	0.008	0.036	0.17	6	-0.18	8	14
G1/S progression	-0.001	0.04	0.18	6	-0.13	2	8

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.004	0.076	-10000	0	-0.2	69	69
ER alpha/Gai/GDP/Gbeta gamma	-0.092	0.2	-10000	0	-0.45	74	74
AKT1	-0.069	0.24	-10000	0	-0.75	57	57
PIK3CA	0.01	0.019	-10000	0	-0.42	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.073	0.25	-10000	0	-0.77	57	57
mol:Ca2+	-0.017	0.12	-10000	0	-0.34	56	56
IGF1R	-0.006	0.083	-10000	0	-0.42	20	20
E2/ER alpha (dimer)/Striatin	-0.014	0.08	-10000	0	-0.24	58	58
SHC1	0.011	0	-10000	0	-10000	0	0
apoptosis	0.065	0.23	0.71	57	-10000	0	57
RhoA/GTP	-0.018	0.051	-10000	0	-0.27	1	1
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.091	0.15	-10000	0	-0.4	74	74
regulation of stress fiber formation	-0.016	0.059	0.26	3	-10000	0	3
E2/ERA-ERB (dimer)	-0.013	0.079	-10000	0	-0.24	56	56
KRAS	0.01	0.012	-10000	0	-0.27	1	1
G13/GTP	-0.011	0.071	-10000	0	-0.22	56	56
pseudopodium formation	0.016	0.059	-10000	0	-0.26	3	3
E2/ER alpha (dimer)/PELP1	-0.013	0.079	-10000	0	-0.24	56	56
GRB2	0.011	0	-10000	0	-10000	0	0
GNG2	-0.002	0.071	-10000	0	-0.41	15	15
GNAO1	-0.098	0.19	-10000	0	-0.42	131	131
HRAS	0.011	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.059	0.18	-10000	0	-0.5	58	58
E2/ER beta (dimer)	0.008	0	-10000	0	-10000	0	0
mol:GDP	-0.034	0.097	-10000	0	-0.31	56	56
mol:NADP	-0.059	0.18	-10000	0	-0.5	58	58
PIK3R1	0.007	0.038	-10000	0	-0.42	4	4
mol:IP3	-0.019	0.13	-10000	0	-0.36	56	56
IGF-1R heterotetramer	-0.006	0.083	-10000	0	-0.42	20	20
PLCB1	-0.025	0.13	-10000	0	-0.37	57	57
PLCB2	-0.023	0.13	-10000	0	-0.37	56	56
IGF1	-0.074	0.17	-10000	0	-0.42	102	102
mol:L-citrulline	-0.059	0.18	-10000	0	-0.5	58	58
RHOA	0.011	0	-10000	0	-10000	0	0
Gai/GDP	-0.15	0.3	-10000	0	-0.64	132	132
JNK cascade	0.008	0	-10000	0	-10000	0	0
BCAR1	0.011	0	-10000	0	-10000	0	0
ESR2	0.011	0.001	-10000	0	-10000	0	0
GNAQ	0.009	0.027	-10000	0	-0.42	2	2
ESR1	-0.036	0.13	-10000	0	-0.42	56	56
Gq family/GDP/Gbeta gamma	-0.006	0.098	-10000	0	-0.4	16	16
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.01	0.081	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.091	0.15	-10000	0	-0.4	74	74
GNAZ	-0.011	0.094	-10000	0	-0.42	26	26
E2/ER alpha (dimer)	-0.025	0.094	-10000	0	-0.29	56	56
STRN	0.009	0.027	-10000	0	-0.42	2	2
GNAL	-0.063	0.16	-10000	0	-0.42	88	88
PELP1	0.011	0	-10000	0	-10000	0	0
MAPK11	0.013	0.016	-10000	0	-0.24	2	2
GNAI2	0.011	0	-10000	0	-10000	0	0
GNAI3	0.011	0	-10000	0	-10000	0	0
GNAI1	0.002	0.059	-10000	0	-0.42	10	10
HBEGF	-0.1	0.18	-10000	0	-0.37	114	114
cAMP biosynthetic process	-0.052	0.094	-10000	0	-0.2	131	131
SRC	-0.082	0.19	-10000	0	-0.43	74	74
PI3K	0.013	0.03	-10000	0	-0.29	5	5
GNB1	0.011	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.033	0.087	-10000	0	-0.27	56	56
SOS1	0.011	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.1	0.16	-10000	0	-0.37	108	108
Gs family/GTP	-0.053	0.095	-10000	0	-0.21	131	131
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.02	0.006	-10000	0	-10000	0	0
vasodilation	-0.055	0.17	-10000	0	-0.48	58	58
mol:DAG	-0.019	0.13	-10000	0	-0.36	56	56
Gs family/GDP/Gbeta gamma	-0.056	0.1	-10000	0	-0.3	61	61
MSN	0.016	0.062	-10000	0	-0.28	3	3
Gq family/GTP	-0.031	0.13	-10000	0	-0.39	56	56
mol:PI-3-4-5-P3	-0.07	0.24	-10000	0	-0.74	57	57
NRAS	0.011	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.055	0.17	0.48	58	-10000	0	58
GRB2/SOS1	0.016	0	-10000	0	-10000	0	0
RhoA/GDP	-0.032	0.091	-10000	0	-0.29	56	56
NOS3	-0.062	0.19	-10000	0	-0.53	58	58
GNA11	0.001	0.062	-10000	0	-0.42	11	11
MAPKKK cascade	-0.053	0.19	-10000	0	-0.55	58	58
E2/ER alpha (dimer)/PELP1/Src	-0.096	0.16	-10000	0	-0.42	74	74
ruffle organization	0.016	0.059	-10000	0	-0.26	3	3
ROCK2	0.011	0.065	-10000	0	-0.3	3	3
GNA14	-0.034	0.13	-10000	0	-0.42	53	53
GNA15	0.007	0.033	-10000	0	-0.27	7	7
GNA13	0.011	0	-10000	0	-10000	0	0
MMP9	-0.12	0.18	-10000	0	-0.4	109	109
MMP2	-0.081	0.19	-10000	0	-0.42	81	81

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.09	0.18	-9999	-0.32	176	176
MAP3K8	0.003	0.042	-9999	-0.42	5	5
FOS	-0.053	0.12	-9999	-0.38	28	28
PRKCA	-0.02	0.1	-9999	-0.42	33	33
PTPN7	0.005	0.032	-9999	-0.29	6	6
HRAS	0.01	0.001	-9999	-10000	0	0
PRKCB	-0.018	0.1	-9999	-0.42	31	31
NRAS	0.01	0.001	-9999	-10000	0	0
RAS family/GTP	0.014	0.012	-9999	-10000	0	0
MAPK3	-0.021	0.07	-9999	-0.28	4	4
MAP2K1	-0.044	0.15	-9999	-0.41	62	62
ELK1	0.004	0.011	-9999	-10000	0	0
BRAF	-0.037	0.14	-9999	-0.4	59	59
mol:GTP	-0.002	0.003	-9999	-0.005	174	174
MAPK1	-0.021	0.07	-9999	-0.28	4	4
RAF1	-0.037	0.14	-9999	-0.4	59	59
KRAS	0.009	0.013	-9999	-0.27	1	1

×

Syndecan-1-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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.01	0.019	-9999	-0.42	1	1
CCL5	0.006	0.038	-9999	-0.31	7	7
SDCBP	0.011	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.043	0.062	-9999	-0.24	27	27
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.035	0.059	-9999	-0.22	27	27
Syndecan-1/Syntenin	-0.035	0.059	-9999	-0.22	27	27
MAPK3	-0.021	0.055	-9999	-0.3	3	3
HGF/MET	-0.044	0.12	-9999	-0.29	101	101
TGFB1/TGF beta receptor Type II	0.01	0.019	-9999	-0.42	1	1
BSG	0.011	0	-9999	-10000	0	0
keratinocyte migration	-0.035	0.058	-9999	-0.22	27	27
Syndecan-1/RANTES	-0.037	0.064	-9999	-0.23	28	28
Syndecan-1/CD147	-0.028	0.058	-9999	-0.24	12	12
Syndecan-1/Syntenin/PIP2	-0.033	0.056	-9999	-0.21	27	27
LAMA5	0.01	0.012	-9999	-0.27	1	1
positive regulation of cell-cell adhesion	-0.033	0.056	-9999	-0.21	27	27
MMP7	-0.048	0.13	-9999	-0.33	88	88
HGF	-0.069	0.17	-9999	-0.42	96	96
Syndecan-1/CASK	-0.041	0.058	-9999	-0.22	27	27
Syndecan-1/HGF/MET	-0.067	0.11	-9999	-0.26	91	91
regulation of cell adhesion	-0.015	0.054	-9999	-0.28	3	3
HPSE	0.002	0.057	-9999	-0.4	10	10
positive regulation of cell migration	-0.043	0.062	-9999	-0.24	27	27
SDC1	-0.043	0.062	-9999	-0.24	27	27
Syndecan-1/Collagen	-0.043	0.062	-9999	-0.24	27	27
PPIB	0.01	0.012	-9999	-0.27	1	1
MET	0.005	0.045	-9999	-0.34	8	8
PRKACA	0.011	0	-9999	-10000	0	0
MMP9	-0.11	0.14	-9999	-0.27	222	222
MAPK1	-0.021	0.055	-9999	-0.3	3	3
homophilic cell adhesion	-0.042	0.062	-9999	-0.23	27	27
MMP1	-0.11	0.14	-9999	-0.27	212	212

×

Noncanonical Wnt signaling pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.031	0.13	-9999	-0.42	50	50
GNB1/GNG2	-0.029	0.13	-9999	-0.39	33	33
mol:DAG	-0.024	0.12	-9999	-0.4	26	26
PLCG1	-0.025	0.12	-9999	-0.41	26	26
YES1	-0.033	0.13	-9999	-0.41	29	29
FZD3	0.011	0	-9999	-10000	0	0
FZD6	0.01	0.019	-9999	-0.42	1	1
G protein	-0.023	0.12	-9999	-0.37	33	33
MAP3K7	-0.11	0.14	-9999	-0.33	92	92
mol:Ca2+	-0.023	0.11	-9999	-0.38	26	26
mol:IP3	-0.024	0.12	-9999	-0.4	26	26
NLK	-0.004	0.009	-9999	-10000	0	0
GNB1	0.011	0	-9999	-10000	0	0
CAMK2A	-0.12	0.14	-9999	-0.33	110	110
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.041	0.13	-9999	-0.26	113	113
CSNK1A1	0.011	0	-9999	-10000	0	0
GNAS	-0.033	0.13	-9999	-0.41	29	29
GO:0007205	-0.024	0.12	-9999	-0.39	26	26
WNT6	-0.027	0.11	-9999	-0.35	53	53
WNT4	-0.058	0.16	-9999	-0.42	82	82
NFAT1/CK1 alpha	-0.031	0.13	-9999	-0.41	32	32
GNG2	-0.002	0.071	-9999	-0.41	15	15
WNT5A	-0.002	0.072	-9999	-0.42	15	15
WNT11	-0.024	0.1	-9999	-0.3	58	58
CDC42	-0.026	0.12	-9999	-0.39	29	29

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.008	0.033	-10000	0	-0.42	3	3
EPHB2	0.01	0.018	-10000	0	-0.27	2	2
EFNB1	0.017	0.023	-10000	0	-0.28	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.01	0.069	-10000	0	-0.36	3	3
Ephrin B2/EPHB1-2	0	0.067	-10000	0	-0.2	49	49
neuron projection morphogenesis	-0.02	0.055	-10000	0	-0.34	3	3
Ephrin B1/EPHB1-2/Tiam1	0.006	0.074	-10000	0	-0.2	47	47
DNM1	0.008	0.033	-10000	0	-0.42	3	3
cell-cell signaling	0.001	0.002	-10000	0	-10000	0	0
MAP2K4	-0.036	0.16	-10000	0	-0.52	53	53
YES1	-0.076	0.23	-10000	0	-0.76	52	52
Ephrin B1/EPHB1-2/NCK2	0.012	0.063	-10000	0	-0.18	37	37
PI3K	-0.037	0.17	-10000	0	-0.53	53	53
mol:GDP	0.005	0.073	-10000	0	-0.19	47	47
ITGA2B	0.005	0.047	-10000	0	-0.36	8	8
endothelial cell proliferation	0.013	0.022	-10000	0	-0.24	4	4
FYN	-0.076	0.23	-10000	0	-0.76	52	52
MAP3K7	-0.044	0.17	-10000	0	-0.56	52	52
FGR	-0.079	0.23	-10000	0	-0.76	52	52
TIAM1	-0.002	0.072	-10000	0	-0.42	15	15
PIK3R1	0.007	0.038	-10000	0	-0.42	4	4
RGS3	0.011	0	-10000	0	-10000	0	0
cell adhesion	-0.066	0.19	-10000	0	-0.57	53	53
LYN	-0.076	0.23	-10000	0	-0.76	52	52
Ephrin B1/EPHB1-2/Src Family Kinases	-0.071	0.21	-10000	0	-0.7	52	52
Ephrin B1/EPHB1-2	-0.062	0.18	-10000	0	-0.61	52	52
SRC	-0.075	0.23	-10000	0	-0.75	52	52
ITGB3	-0.078	0.17	-10000	0	-0.41	107	107
EPHB1	-0.028	0.12	-10000	0	-0.41	47	47
EPHB4	0.01	0.019	-10000	0	-0.42	1	1
RAC1	0.011	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.013	0.022	-10000	0	-0.24	4	4
alphaIIb/beta3 Integrin	-0.051	0.12	-10000	0	-0.28	114	114
BLK	-0.074	0.23	-10000	0	-0.76	52	52
HCK	-0.075	0.23	-10000	0	-0.75	52	52
regulation of stress fiber formation	-0.011	0.062	0.18	37	-10000	0	37
MAPK8	-0.031	0.16	-10000	0	-0.5	52	52
Ephrin B1/EPHB1-2/RGS3	0.012	0.063	-10000	0	-0.18	37	37
endothelial cell migration	-0.044	0.14	-10000	0	-0.46	54	54
NCK2	0.011	0	-10000	0	-10000	0	0
PTPN13	-0.046	0.16	-10000	0	-0.53	52	52
regulation of focal adhesion formation	-0.011	0.062	0.18	37	-10000	0	37
chemotaxis	-0.011	0.062	0.18	37	-10000	0	37
PIK3CA	0.01	0.019	-10000	0	-0.42	1	1
Rac1/GTP	-0.02	0.056	-10000	0	-0.35	3	3
angiogenesis	-0.061	0.18	-10000	0	-0.6	52	52
LCK	-0.075	0.23	-10000	0	-0.75	52	52

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.075	0.095	-9999	-0.18	224	224
TP53	-0.018	0.024	-9999	-0.33	1	1
Senescence	-0.018	0.024	-9999	-0.33	1	1
Apoptosis	-0.018	0.024	-9999	-0.33	1	1
Activated_Oncogenes	0	0	-9999	-10000	0	0
MDM2	0.038	0.043	-9999	-10000	0	0
MDM4	0.011	0	-9999	-10000	0	0

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.002	0.078	-9999	-0.23	47	47
NF kappa B1 p50/RelA/I kappa B alpha	0.017	0.066	-9999	-0.26	5	5
AP1	-0.09	0.12	-9999	-0.3	76	76
mol:PIP3	-0.032	0.068	-9999	-0.31	16	16
AKT1	0.026	0.059	-9999	-0.27	9	9
PTK2B	0.005	0.058	-9999	-0.2	30	30
RHOA	0.018	0.03	-9999	-10000	0	0
PIK3CB	0.01	0	-9999	-10000	0	0
mol:Ca2+	0.002	0.061	-9999	-0.2	20	20
MAGI3	0.011	0	-9999	-10000	0	0
RELA	0.011	0	-9999	-10000	0	0
apoptosis	-0.014	0.082	-9999	-0.23	52	52
HRAS/GDP	0.008	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.007	0.065	-9999	-0.22	16	16
NF kappa B1 p50/RelA	-0.016	0.07	-9999	-0.32	10	10
endothelial cell migration	-0.012	0.13	-9999	-0.44	37	37
ADCY4	-0.053	0.15	-9999	-0.38	65	65
ADCY5	-0.077	0.16	-9999	-0.39	79	79
ADCY6	-0.039	0.13	-9999	-0.34	49	49
ADCY7	-0.039	0.13	-9999	-0.34	49	49
ADCY1	-0.047	0.14	-9999	-0.38	56	56
ADCY2	-0.15	0.19	-9999	-0.41	137	137
ADCY3	-0.04	0.13	-9999	-0.35	50	50
ADCY8	-0.063	0.14	-9999	-0.38	55	55
ADCY9	-0.066	0.16	-9999	-0.38	83	83
GSK3B	0.01	0.056	-9999	-0.2	25	25
arachidonic acid secretion	-0.045	0.14	-9999	-0.38	42	42
GNG2	-0.002	0.071	-9999	-0.41	15	15
TRIP6	0.014	0.036	-9999	-0.36	4	4
GNAO1	-0.061	0.14	-9999	-0.26	151	151
HRAS	0.011	0	-9999	-10000	0	0
NFKBIA	0.009	0.071	-9999	-0.25	12	12
GAB1	0.007	0.038	-9999	-0.42	4	4
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.005	0.15	-9999	-0.85	15	15
JUN	0.006	0.046	-9999	-0.42	6	6
LPA/LPA2/NHERF2	0.012	0.022	-9999	-0.14	3	3
TIAM1	-0.028	0.17	-9999	-1	15	15
PIK3R1	0.007	0.038	-9999	-0.42	4	4
mol:IP3	0.002	0.061	-9999	-0.2	20	20
PLCB3	0.017	0.019	-9999	-10000	0	0
FOS	-0.13	0.2	-9999	-0.42	174	174
positive regulation of mitosis	-0.045	0.14	-9999	-0.38	42	42
LPA/LPA1-2-3	-0.016	0.088	-9999	-0.23	52	52
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.011	0	-9999	-10000	0	0
stress fiber formation	0.004	0.067	-9999	-0.26	14	14
GNAZ	-0.01	0.091	-9999	-0.25	61	61
EGFR/PI3K-beta/Gab1	-0.033	0.071	-9999	-0.33	16	16
positive regulation of dendritic cell cytokine production	-0.02	0.086	-9999	-0.23	52	52
LPA/LPA2/MAGI-3	0.012	0.021	-9999	-0.14	3	3
ARHGEF1	0.014	0.061	-9999	-0.19	37	37
GNAI2	0.002	0.072	-9999	-0.24	37	37
GNAI3	0.002	0.072	-9999	-0.24	37	37
GNAI1	-0.002	0.081	-9999	-0.25	45	45
LPA/LPA3	-0.028	0.081	-9999	-0.21	79	79
LPA/LPA2	0.004	0.026	-9999	-0.18	3	3
LPA/LPA1	-0.007	0.084	-9999	-0.3	37	37
HB-EGF/EGFR	-0.054	0.09	-9999	-0.32	14	14
HBEGF	-0.066	0.096	-9999	-0.18	223	223
mol:DAG	0.002	0.061	-9999	-0.2	20	20
cAMP biosynthetic process	-0.075	0.15	-9999	-0.29	135	135
NFKB1	0.01	0.019	-9999	-0.42	1	1
SRC	0.011	0	-9999	-10000	0	0
GNB1	0.01	0	-9999	-10000	0	0
LYN	0.009	0.071	-9999	-0.24	22	22
GNAQ	-0.005	0.056	-9999	-0.22	21	21
LPAR2	0.009	0.022	-9999	-0.27	3	3
LPAR3	-0.038	0.12	-9999	-0.3	79	79
LPAR1	-0.006	0.084	-9999	-0.45	15	15
IL8	-0.054	0.11	-9999	-0.33	34	34
PTK2	-0.01	0.082	-9999	-0.23	34	34
Rac1/GDP	0.008	0	-9999	-10000	0	0
CASP3	-0.014	0.082	-9999	-0.23	52	52
EGFR	-0.001	0.068	-9999	-0.41	14	14
PLCG1	-0.011	0.071	-9999	-0.21	40	40
PLD2	-0.01	0.083	-9999	-0.21	48	48
G12/G13	0.009	0.065	-9999	-0.22	37	37
PI3K-beta	-0.016	0.053	-9999	-0.31	9	9
cell migration	-0.015	0.05	-9999	-0.24	17	17
SLC9A3R2	0.011	0	-9999	-10000	0	0
PXN	0.004	0.068	-9999	-0.26	14	14
HRAS/GTP	-0.046	0.14	-9999	-0.39	42	42
RAC1	0.011	0	-9999	-10000	0	0
MMP9	-0.11	0.14	-9999	-0.27	222	222
PRKCE	0.01	0.002	-9999	-10000	0	0
PRKCD	0.007	0.059	-9999	-0.22	7	7
Gi(beta/gamma)	-0.04	0.13	-9999	-0.37	42	42
mol:LPA	-0.004	0.035	-9999	-0.16	22	22
TRIP6/p130 Cas/FAK1/Paxillin	-0.024	0.07	-9999	-0.38	9	9
MAPKKK cascade	-0.045	0.14	-9999	-0.38	42	42
contractile ring contraction involved in cytokinesis	0.018	0.03	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.029	0.096	-9999	-0.26	69	69
GNA15	-0.006	0.055	-9999	-0.22	19	19
GNA12	0.011	0	-9999	-10000	0	0
GNA13	0.011	0	-9999	-10000	0	0
MAPT	0.007	0.067	-9999	-0.23	16	16
GNA11	-0.01	0.063	-9999	-0.22	30	30
Rac1/GTP	-0.006	0.16	-9999	-0.91	15	15
MMP2	-0.012	0.13	-9999	-0.44	37	37

×

Lissencephaly gene (LIS1) in neuronal migration and development

Figure S43. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S43. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.011	0	-9999	-10000	0	0
VLDLR	0.009	0.027	-9999	-0.42	2	2
LRPAP1	0.011	0	-9999	-10000	0	0
NUDC	0.011	0	-9999	-10000	0	0
RELN/LRP8	-0.074	0.12	-9999	-0.23	187	187
CaM/Ca2+	0.008	0	-9999	-10000	0	0
KATNA1	0.011	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.061	0.11	-9999	-0.2	189	189
IQGAP1/CaM	0.016	0	-9999	-10000	0	0
DAB1	0.001	0.043	-9999	-0.27	12	12
IQGAP1	0.011	0	-9999	-10000	0	0
PLA2G7	0.009	0.026	-9999	-0.32	3	3
CALM1	0.011	0	-9999	-10000	0	0
DYNLT1	0.011	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	0.014	0.017	-9999	-0.18	4	4
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.011	0	-9999	-10000	0	0
CDK5R1	0.01	0.012	-9999	-0.27	1	1
LIS1/Poliovirus Protein 3A	0.013	0	-9999	-10000	0	0
CDK5R2	-0.022	0.085	-9999	-0.27	53	53
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.08	0.12	-9999	-0.24	188	188
YWHAE	0.011	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.032	0.092	-9999	-0.2	15	15
MAP1B	-0.013	0.057	-9999	-0.25	27	27
RAC1	0.017	0	-9999	-10000	0	0
p35/CDK5	-0.042	0.098	-9999	-0.26	3	3
RELN	-0.15	0.2	-9999	-0.41	191	191
PAFAH/LIS1	0.02	0.015	-9999	-0.23	1	1
LIS1/CLIP170	0.021	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.04	0.056	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.053	0.1	-9999	-0.19	188	188
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.041	0.095	-9999	-0.22	15	15
LIS1/IQGAP1	0.021	0	-9999	-10000	0	0
RHOA	0.017	0	-9999	-10000	0	0
PAFAH1B1	0.017	0	-9999	-10000	0	0
PAFAH1B3	0.006	0.037	-9999	-0.27	9	9
PAFAH1B2	0.01	0.019	-9999	-0.42	1	1
MAP1B/LIS1/Dynein heavy chain	0.011	0.038	-9999	-0.15	27	27
NDEL1/Katanin 60/Dynein heavy chain	-0.026	0.089	-9999	-0.24	2	2
LRP8	0.008	0.025	-9999	-0.27	4	4
NDEL1/Katanin 60	-0.032	0.092	-9999	-0.25	2	2
P39/CDK5	-0.045	0.11	-9999	-0.27	18	18
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.021	0	-9999	-10000	0	0
CDK5	-0.051	0.1	-9999	-0.18	189	189
PPP2R5D	0.011	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.018	0	-9999	-10000	0	0
CSNK2A1	0.011	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.055	0.1	-9999	-0.19	188	188
RELN/VLDLR	-0.06	0.11	-9999	-0.21	188	188
CDC42	0.017	0	-9999	-10000	0	0

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.26	0.39	-10000	0	-1.1	47	47
STAT6 (cleaved dimer)	-0.29	0.36	-10000	0	-0.91	94	94
IGHG1	-0.091	0.15	-10000	0	-0.36	16	16
IGHG3	-0.25	0.38	-10000	0	-0.92	80	80
AKT1	-0.11	0.22	-10000	0	-0.7	15	15
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.071	0.16	-10000	0	-0.59	11	11
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.13	0.24	-10000	0	-0.66	34	34
THY1	-0.26	0.39	-10000	0	-1.1	47	47
MYB	-0.027	0.096	-10000	0	-0.27	68	68
HMGA1	-0.033	0.1	-10000	0	-0.27	79	79
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.15	0.24	-10000	0	-0.64	40	40
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.12	0.22	-10000	0	-0.73	13	13
SP1	0.017	0.002	-10000	0	-10000	0	0
INPP5D	0.01	0.019	-10000	0	-0.42	1	1
SOCS5	0.017	0.014	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.24	0.39	-10000	0	-0.99	69	69
SOCS1	-0.16	0.28	-10000	0	-0.72	42	42
SOCS3	-0.12	0.24	-10000	0	-1.1	10	10
FCER2	-0.2	0.31	-10000	0	-0.84	47	47
PARP14	0.011	0.001	-10000	0	-10000	0	0
CCL17	-0.26	0.39	-10000	0	-1.1	47	47
GRB2	0.011	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.088	0.18	-10000	0	-0.73	5	5
T cell proliferation	-0.26	0.4	-10000	0	-1.1	60	60
IL4R/JAK1	-0.26	0.4	-10000	0	-1	59	59
EGR2	-0.29	0.48	-10000	0	-1.3	62	62
JAK2	-0.01	0.063	-10000	0	-0.43	9	9
JAK3	0.013	0.022	-10000	0	-0.27	3	3
PIK3R1	0.007	0.038	-10000	0	-0.42	4	4
JAK1	0.006	0.034	-10000	0	-0.41	3	3
COL1A2	-0.085	0.19	-10000	0	-1.4	5	5
CCL26	-0.26	0.39	-10000	0	-1.1	48	48
IL4R	-0.27	0.42	-10000	0	-1.1	58	58
PTPN6	0.017	0.017	-10000	0	-0.25	1	1
IL13RA2	-0.26	0.4	-10000	0	-1	58	58
IL13RA1	-0.002	0.028	-10000	0	-10000	0	0
IRF4	-0.062	0.22	-10000	0	-1.1	17	17
ARG1	-0.058	0.12	-10000	0	-10000	0	0
CBL	-0.13	0.23	-10000	0	-0.6	39	39
GTF3A	0.017	0	-10000	0	-10000	0	0
PIK3CA	0.01	0.019	-10000	0	-0.42	1	1
IL13RA1/JAK2	-0.009	0.054	-10000	0	-0.28	9	9
IRF4/BCL6	-0.056	0.2	-10000	0	-0.98	17	17
CD40LG	0.007	0.061	-10000	0	-0.42	10	10
MAPK14	-0.13	0.24	-10000	0	-0.68	28	28
mitosis	-0.11	0.21	-10000	0	-0.66	15	15
STAT6	-0.29	0.44	-10000	0	-1.1	74	74
SPI1	0.011	0.022	-10000	0	-0.27	3	3
RPS6KB1	-0.098	0.2	-10000	0	-0.63	15	15
STAT6 (dimer)	-0.29	0.44	-10000	0	-1.1	74	74
STAT6 (dimer)/PARP14	-0.27	0.41	-10000	0	-1	74	74
mast cell activation	0.006	0.012	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.1	0.2	-10000	0	-0.68	11	11
FRAP1	-0.11	0.22	-10000	0	-0.7	15	15
LTA	-0.26	0.39	-10000	0	-1.1	47	47
FES	0.01	0.019	-10000	0	-0.42	1	1
T-helper 1 cell differentiation	0.29	0.44	1.1	74	-10000	0	74
CCL11	-0.32	0.48	-10000	0	-1.2	84	84
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.1	0.2	-10000	0	-0.7	10	10
IL2RG	0.01	0.039	-10000	0	-0.32	7	7
IL10	-0.26	0.39	-10000	0	-1.1	46	46
IRS1	-0.029	0.12	-10000	0	-0.42	47	47
IRS2	-0.045	0.14	-10000	0	-0.42	67	67
IL4	-0.062	0.11	-10000	0	-10000	0	0
IL5	-0.26	0.39	-10000	0	-1.1	51	51
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.22	0.34	-10000	0	-0.85	59	59
COL1A1	-0.079	0.15	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.26	0.4	-10000	0	-1.2	46	46
IL2R gamma/JAK3	0.016	0.035	-10000	0	-0.25	8	8
TFF3	-0.31	0.45	-10000	0	-1.2	73	73
ALOX15	-0.27	0.4	-10000	0	-1.1	53	53
MYBL1	0.011	0	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.22	0.33	-10000	0	-0.85	62	62
SHC1	0.011	0	-10000	0	-10000	0	0
CEBPB	0.013	0.003	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.13	0.23	-10000	0	-0.67	23	23
mol:PI-3-4-5-P3	-0.11	0.22	-10000	0	-0.7	15	15
PI3K	-0.12	0.23	-10000	0	-0.75	15	15
DOK2	0.008	0.029	-10000	0	-0.31	4	4
ETS1	0.015	0.033	-10000	0	-0.38	3	3
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.079	0.17	-10000	0	-0.7	5	5
ITGB3	-0.4	0.59	-10000	0	-1.3	123	123
PIGR	-0.32	0.46	-10000	0	-1.2	70	70
IGHE	0.02	0.034	-10000	0	-10000	0	0
MAPKKK cascade	-0.078	0.16	-10000	0	-0.68	5	5
BCL6	0.009	0.019	-10000	0	-0.42	1	1
OPRM1	-0.26	0.39	-10000	0	-1.1	48	48
RETNLB	-0.26	0.39	-10000	0	-1.1	51	51
SELP	-0.58	0.68	-10000	0	-1.3	225	225
AICDA	-0.25	0.38	-10000	0	-1.1	46	46

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.002	0.069	-9999	-0.29	28	28
PDGFRB	-0.008	0.086	-9999	-0.42	21	21
SPHK1	-0.015	0.025	-9999	-10000	0	0
mol:S1P	-0.018	0.032	-9999	-10000	0	0
S1P1/S1P/Gi	-0.091	0.2	-9999	-0.44	96	96
GNAO1	-0.1	0.19	-9999	-0.42	131	131
PDGFB-D/PDGFRB/PLCgamma1	-0.076	0.19	-9999	-0.4	96	96
PLCG1	-0.08	0.19	-9999	-0.41	97	97
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.008	0.086	-9999	-0.42	21	21
GNAI2	0.01	0.004	-9999	-10000	0	0
GNAI3	0.009	0.004	-9999	-10000	0	0
GNAI1	0.001	0.06	-9999	-0.42	10	10
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.001	0.059	-9999	-0.24	28	28
S1P1/S1P	-0.006	0.077	-9999	-0.27	16	16
negative regulation of cAMP metabolic process	-0.088	0.2	-9999	-0.43	96	96
MAPK3	-0.1	0.24	-9999	-0.57	88	88
calcium-dependent phospholipase C activity	-0.002	0.003	-9999	-10000	0	0
Rac1/GDP	0.008	0	-9999	-10000	0	0
RhoA/GDP	0.008	0	-9999	-10000	0	0
KDR	-0.013	0.097	-9999	-0.42	28	28
PLCB2	0	0.071	-9999	-0.25	14	14
RAC1	0.011	0	-9999	-10000	0	0
RhoA/GTP	-0.023	0.057	-9999	-0.24	14	14
receptor internalization	-0.025	0.064	-9999	-0.26	16	16
PTGS2	-0.15	0.36	-9999	-0.98	72	72
Rac1/GTP	-0.023	0.057	-9999	-0.24	14	14
RHOA	0.011	0	-9999	-10000	0	0
VEGFA	0.01	0.003	-9999	-10000	0	0
negative regulation of T cell proliferation	-0.088	0.2	-9999	-0.43	96	96
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.012	0.095	-9999	-0.42	26	26
MAPK1	-0.1	0.24	-9999	-0.56	92	92
S1P1/S1P/PDGFB-D/PDGFRB	-0.011	0.1	-9999	-0.32	27	27
ABCC1	0.01	0.002	-9999	-10000	0	0

×

Syndecan-4-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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.014	0.044	-9999	-0.41	5	5
Syndecan-4/Syndesmos	-0.009	0.078	-9999	-0.24	3	3
positive regulation of JNK cascade	-0.12	0.12	-9999	-0.35	54	54
Syndecan-4/ADAM12	-0.011	0.08	-9999	-0.24	3	3
CCL5	0.006	0.038	-9999	-0.31	7	7
Rac1/GDP	0.008	0	-9999	-10000	0	0
DNM2	0.011	0	-9999	-10000	0	0
ITGA5	0.01	0.019	-9999	-0.42	1	1
SDCBP	0.011	0	-9999	-10000	0	0
PLG	-0.049	0.14	-9999	-0.39	76	76
ADAM12	0.003	0.046	-9999	-0.27	14	14
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.011	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.038	0.04	-9999	-0.12	7	7
Syndecan-4/Laminin alpha1	-0.029	0.11	-9999	-0.3	28	28
Syndecan-4/CXCL12/CXCR4	-0.12	0.12	-9999	-0.36	54	54
Syndecan-4/Laminin alpha3	-0.014	0.084	-9999	-0.29	5	5
MDK	0.01	0.012	-9999	-0.27	1	1
Syndecan-4/FZD7	-0.051	0.11	-9999	-0.39	15	15
Syndecan-4/Midkine	-0.01	0.079	-9999	-0.26	4	4
FZD7	-0.08	0.18	-9999	-0.42	109	109
Syndecan-4/FGFR1/FGF	-0.12	0.11	-9999	-0.36	51	51
THBS1	-0.056	0.16	-9999	-0.42	80	80
integrin-mediated signaling pathway	-0.014	0.084	-9999	-0.31	7	7
positive regulation of MAPKKK cascade	-0.12	0.12	-9999	-0.35	54	54
Syndecan-4/TACI	-0.014	0.081	-9999	-0.27	5	5
CXCR4	0.011	0	-9999	-10000	0	0
cell adhesion	0.013	0.052	-9999	-0.17	33	33
Syndecan-4/Dynamin	-0.009	0.078	-9999	-0.24	3	3
Syndecan-4/TSP1	-0.04	0.11	-9999	-0.36	16	16
Syndecan-4/GIPC	-0.009	0.078	-9999	-10000	0	0
Syndecan-4/RANTES	-0.011	0.081	-9999	-0.29	5	5
ITGB1	0.011	0	-9999	-10000	0	0
LAMA1	-0.11	0.14	-9999	-0.27	223	223
LAMA3	0	0.067	-9999	-0.42	13	13
RAC1	0.011	0	-9999	-10000	0	0
PRKCA	-0.006	0.1	-9999	-0.38	33	33
Syndecan-4/alpha-Actinin	-0.009	0.078	-9999	-0.24	3	3
TFPI	-0.039	0.14	-9999	-0.42	60	60
F2	-0.018	0.078	-9999	-0.27	44	44
alpha5/beta1 Integrin	0.015	0.013	-9999	-0.29	1	1
positive regulation of cell adhesion	-0.06	0.096	-9999	-0.3	32	32
ACTN1	0.011	0	-9999	-10000	0	0
TNC	-0.001	0.068	-9999	-0.41	14	14
Syndecan-4/CXCL12	-0.13	0.13	-9999	-0.38	56	56
FGF6	0	0	-9999	-10000	0	0
RHOA	0.011	0	-9999	-10000	0	0
CXCL12	-0.26	0.21	-9999	-0.42	319	319
TNFRSF13B	0	0.047	-9999	-0.27	15	15
FGF2	-0.24	0.21	-9999	-0.42	301	301
FGFR1	0.01	0.019	-9999	-0.42	1	1
Syndecan-4/PI-4-5-P2	-0.016	0.077	-9999	-0.24	3	3
mol:GDP	0	0	-9999	-10000	0	0
FN1	0.011	0.041	-9999	-0.4	5	5
cell migration	-0.017	0.018	-9999	-10000	0	0
PRKCD	0.015	0.008	-9999	-10000	0	0
vasculogenesis	-0.039	0.1	-9999	-0.35	16	16
SDC4	-0.017	0.081	-9999	-0.26	3	3
Syndecan-4/Tenascin C	-0.014	0.086	-9999	-0.32	7	7
Syndecan-4/PI-4-5-P2/PKC alpha	-0.03	0.032	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.009	0.078	-9999	-0.24	3	3
MMP9	-0.11	0.14	-9999	-0.27	222	222
Rac1/GTP	0.013	0.053	-9999	-0.18	30	30
cytoskeleton organization	-0.009	0.076	-9999	-0.23	3	3
GIPC1	0.011	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.032	0.1	-9999	-0.36	18	18

×

S1P5 pathway

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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.036	0.1	0.34	19	-10000	0	19
GNAI2	0.011	0	-10000	0	-10000	0	0
S1P/S1P5/G12	0.01	0.028	-10000	0	-0.15	15	15
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.098	0.19	-10000	0	-0.42	131	131
RhoA/GTP	-0.036	0.11	-10000	0	-0.35	19	19
negative regulation of cAMP metabolic process	-0.045	0.12	-10000	0	-0.22	133	133
GNAZ	-0.011	0.094	-10000	0	-0.42	26	26
GNAI3	0.011	0	-10000	0	-10000	0	0
GNA12	0.011	0	-10000	0	-10000	0	0
S1PR5	0.002	0.05	-10000	0	-0.28	15	15
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.046	0.12	-10000	0	-0.22	133	133
RhoA/GDP	0.008	0	-10000	0	-10000	0	0
RHOA	0.011	0	-10000	0	-10000	0	0
GNAI1	0.002	0.059	-10000	0	-0.42	10	10

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.014	0	-9999	-10000	0	0
ARNO/beta Arrestin1-2	-0.018	0.067	-9999	-10000	0	0
EGFR	-0.001	0.068	-9999	-0.41	14	14
EPHA2	0.011	0	-9999	-10000	0	0
USP6	0.011	0	-9999	-10000	0	0
IQSEC1	0.01	0.019	-9999	-0.42	1	1
EGFR/EGFR/EGF/EGF	-0.001	0.063	-9999	-0.23	33	33
ARRB2	0.007	0.002	-9999	-10000	0	0
mol:GTP	0.015	0.01	-9999	-0.14	1	1
ARRB1	0.01	0.019	-9999	-0.42	1	1
FBXO8	0.011	0	-9999	-10000	0	0
TSHR	-0.004	0.06	-9999	-0.29	20	20
EGF	-0.002	0.058	-9999	-0.29	20	20
somatostatin receptor activity	0	0	-9999	-0.001	80	80
ARAP2	0.009	0.027	-9999	-0.42	2	2
mol:GDP	-0.05	0.093	-9999	-0.22	81	81
mol:PI-3-4-5-P3	0	0	-9999	-0.001	46	46
ITGA2B	0.005	0.047	-9999	-0.36	8	8
ARF6	0.011	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.026	0.017	-9999	-0.2	2	2
ADAP1	0.011	0	-9999	-10000	0	0
KIF13B	0.011	0	-9999	-10000	0	0
HGF/MET	-0.044	0.12	-9999	-0.29	101	101
PXN	0.011	0	-9999	-10000	0	0
ARF6/GTP	-0.046	0.096	-9999	-0.22	72	72
EGFR/EGFR/EGF/EGF/ARFGEP100	0.007	0.054	-9999	-0.24	16	16
ADRB2	-0.06	0.16	-9999	-0.42	85	85
receptor agonist activity	0	0	-9999	0	79	79
actin filament binding	0	0	-9999	0	77	77
SRC	0.011	0	-9999	-10000	0	0
ITGB3	-0.078	0.17	-9999	-0.41	107	107
GNAQ	0.009	0.027	-9999	-0.42	2	2
EFA6/PI-4-5-P2	0	0	-9999	-0.001	71	71
ARF6/GDP	0.015	0.046	-9999	-0.29	3	3
ARF6/GDP/GULP/ACAP1	-0.049	0.12	-9999	-0.29	65	65
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.023	0.096	-9999	-0.2	110	110
ACAP1	0.008	0.029	-9999	-0.31	4	4
ACAP2	0.01	0.019	-9999	-0.42	1	1
LHCGR/beta Arrestin2	0.001	0.004	-9999	-10000	0	0
EFNA1	0.01	0.018	-9999	-0.27	2	2
HGF	-0.07	0.17	-9999	-0.42	96	96
CYTH3	0.009	0	-9999	-10000	0	0
CYTH2	0.007	0.002	-9999	-10000	0	0
NCK1	0.009	0.027	-9999	-0.42	2	2
fibronectin binding	0	0	-9999	0	60	60
endosomal lumen acidification	0	0	-9999	0	56	56
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.033	0.13	-9999	-0.42	52	52
GNAQ/ARNO	0.011	0.014	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	0	1	1
PIP3-E	0	0	-9999	0	17	17
MET	0.005	0.045	-9999	-0.34	8	8
GNA14	-0.034	0.13	-9999	-0.42	53	53
GNA15	0.007	0.033	-9999	-0.27	7	7
GIT1	0.011	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	71	71
GNA11	0.001	0.062	-9999	-0.42	11	11
LHCGR	0.001	0.003	-9999	-10000	0	0
AGTR1	-0.1	0.19	-9999	-0.42	136	136
desensitization of G-protein coupled receptor protein signaling pathway	0.001	0.004	-9999	-10000	0	0
IPCEF1/ARNO	0.007	0.04	-9999	-10000	0	0
alphaIIb/beta3 Integrin	-0.051	0.12	-9999	-0.28	114	114

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.019	0.059	0.2	50	-10000	0	50
RFC1	0.019	0.059	0.2	50	-10000	0	50
PRKDC	0.019	0.059	0.2	50	-10000	0	50
RIPK1	0.011	0.002	-10000	0	-10000	0	0
CASP7	-0.002	0.017	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1	0.014	0.06	0.19	46	-0.21	5	51
MAP2K4	0.033	0.061	-10000	0	-0.24	16	16
mol:ceramide	0.026	0.046	-10000	0	-0.24	3	3
GSN	0.016	0.065	0.2	49	-0.23	7	56
FASLG/FAS/FADD/FAF1/Caspase 8	0.032	0.053	0.17	45	-0.23	3	48
FAS	0.007	0.042	-10000	0	-0.42	5	5
BID	0.001	0.017	0.27	2	-10000	0	2
MAP3K1	0.032	0.04	-10000	0	-10000	0	0
MAP3K7	0.01	0.002	-10000	0	-10000	0	0
RB1	0.018	0.061	0.2	49	-0.23	2	51
CFLAR	0.011	0.002	-10000	0	-10000	0	0
HGF/MET	-0.054	0.13	-10000	0	-0.26	137	137
ARHGDIB	0.019	0.059	0.2	50	-10000	0	50
FADD	0.011	0.003	-10000	0	-10000	0	0
actin filament polymerization	-0.016	0.065	0.23	7	-0.2	49	56
NFKB1	-0.01	0.048	-10000	0	-0.65	1	1
MAPK8	0.031	0.095	-10000	0	-0.41	20	20
DFFA	0.019	0.059	0.2	50	-10000	0	50
DNA fragmentation during apoptosis	0.019	0.059	0.2	50	-10000	0	50
FAS/FADD/MET	0.016	0.037	-10000	0	-0.23	9	9
CFLAR/RIP1	0.015	0.003	-10000	0	-10000	0	0
FAIM3	0.009	0.027	-10000	0	-0.42	2	2
FAF1	0.011	0.005	-10000	0	-10000	0	0
PARP1	0.019	0.059	0.2	50	-10000	0	50
DFFB	0.019	0.059	0.2	50	-10000	0	50
CHUK	-0.009	0.043	-10000	0	-0.6	1	1
FASLG	0.003	0.048	-10000	0	-0.31	11	11
FAS/FADD	0.013	0.03	-10000	0	-0.28	5	5
HGF	-0.069	0.17	-10000	0	-0.42	96	96
LMNA	0.018	0.055	0.18	50	-10000	0	50
CASP6	0.019	0.059	0.2	50	-10000	0	50
CASP10	0.01	0.019	-10000	0	-0.42	1	1
CASP3	0.023	0.069	0.23	50	-10000	0	50
PTPN13	-0.033	0.13	-10000	0	-0.42	52	52
CASP8	0.001	0.021	0.33	2	-10000	0	2
IL6	-0.017	0.23	-10000	0	-1.2	20	20
MET	0.005	0.045	-10000	0	-0.34	8	8
ICAD/CAD	0.018	0.055	0.18	50	-10000	0	50
FASLG/FAS/FADD/FAF1/Caspase 10	0.026	0.046	-10000	0	-0.25	3	3
activation of caspase activity by cytochrome c	0.001	0.017	0.27	2	-10000	0	2
PAK2	0.019	0.059	0.2	50	-10000	0	50
BCL2	-0.029	0.12	-10000	0	-0.42	48	48

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.011	0	-9999	-10000	0	0
EGFR	-0.001	0.068	-9999	-0.41	14	14
EGF/EGFR	-0.066	0.1	-9999	-0.2	162	162
EGF/EGFR dimer/SHC/GRB2/SOS1	0.02	0.045	-9999	-0.2	15	15
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.12	0.2	-9999	-0.42	151	151
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.002	0.058	-9999	-0.29	20	20
EGF/EGFR dimer/SHC	0.008	0.053	-9999	-0.24	15	15
mol:GDP	-0.009	0.037	-9999	-0.19	15	15
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.005	0.05	-9999	-0.42	7	7
GRB2/SOS1	0.016	0	-9999	-10000	0	0
HRAS/GTP	-0.008	0.033	-9999	-0.28	1	1
SHC1	0.011	0	-9999	-10000	0	0
HRAS/GDP	-0.008	0.034	-9999	-0.29	1	1
FRAP1	0.016	0.042	-9999	-0.18	15	15
EGF/EGFR dimer	0	0.063	-9999	-0.23	33	33
SOS1	0.011	0	-9999	-10000	0	0
GRB2	0.011	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.077	0.14	-9999	-0.29	155	155

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.005	0.05	-10000	0	-1.1	1	1
VDR	0.005	0.039	-10000	0	-0.27	10	10
FAM120B	0.011	0	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.021	0.073	-10000	0	-0.25	12	12
RXRs/LXRs/DNA/Oxysterols	0.027	0.072	-10000	0	-0.46	2	2
MED1	0.011	0	-10000	0	-10000	0	0
mol:9cRA	0.004	0.005	-10000	0	-10000	0	0
RARs/THRs/DNA/Src-1	-0.026	0.11	-10000	0	-0.21	117	117
RXRs/NUR77	-0.039	0.12	-10000	0	-0.22	148	148
RXRs/PPAR	0	0.083	-10000	0	-0.2	75	75
NCOR2	0.011	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.004	0.026	-10000	0	-0.18	10	10
RARs/VDR/DNA/Vit D3	0.019	0.035	-10000	0	-0.19	10	10
RARA	0.011	0	-10000	0	-10000	0	0
NCOA1	0.01	0.019	-10000	0	-0.42	1	1
VDR/VDR/DNA	0.005	0.039	-10000	0	-0.27	10	10
RARs/RARs/DNA/9cRA	0.017	0.03	-10000	0	-0.19	10	10
RARG	0.011	0	-10000	0	-10000	0	0
RPS6KB1	0.008	0.028	-10000	0	-0.4	1	1
RARs/THRs/DNA/SMRT	-0.025	0.1	-10000	0	-0.21	117	117
THRA	0.003	0.056	-10000	0	-0.42	9	9
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.004	0.026	-10000	0	-0.18	10	10
RXRs/PPAR/9cRA/PGJ2/DNA	0.009	0.074	0.28	1	-0.21	48	49
NR1H4	-0.007	0.051	-10000	0	-0.27	18	18
RXRs/LXRs/DNA	0.03	0.071	-10000	0	-0.22	11	11
NR1H2	0.015	0.004	-10000	0	-10000	0	0
NR1H3	0.015	0.013	-10000	0	-0.26	1	1
RXRs/VDR/DNA/Vit D3	0.008	0.07	-10000	0	-0.19	48	48
NR4A1	-0.082	0.18	-10000	0	-0.42	111	111
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	0.005	0.062	-10000	0	-0.21	14	14
RXRG	-0.031	0.13	-10000	0	-0.39	57	57
RXR alpha/CCPG	0.019	0.003	-10000	0	-10000	0	0
RXRA	0.014	0.004	-10000	0	-10000	0	0
RXRB	0.015	0.004	-10000	0	-10000	0	0
THRB	-0.077	0.17	-10000	0	-0.42	105	105
PPARG	-0.014	0.099	-10000	0	-0.42	29	29
PPARD	0.011	0	-10000	0	-10000	0	0
TNF	0.025	0.094	-10000	0	-1	2	2
mol:Oxysterols	0.004	0.005	-10000	0	-10000	0	0
cholesterol transport	0.027	0.071	-10000	0	-0.45	2	2
PPARA	0.011	0	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.002	0.059	-10000	0	-0.42	10	10
RXRs/NUR77/BCL2	-0.066	0.14	-10000	0	-0.25	172	172
SREBF1	0.032	0.066	-10000	0	-0.42	2	2
RXRs/RXRs/DNA/9cRA	0.009	0.074	0.27	1	-0.21	48	49
ABCA1	0.032	0.066	-10000	0	-0.5	1	1
RARs/THRs	-0.02	0.099	-10000	0	-0.2	117	117
RXRs/FXR	0.002	0.079	-10000	0	-0.22	48	48
BCL2	-0.029	0.12	-10000	0	-0.42	48	48

×

TCGA08_rtk_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
PDGFRA	-0.1	0.19	-10000	0	-0.42	133	133
HRAS	0.011	0	-10000	0	-10000	0	0
EGFR	-0.001	0.068	-10000	0	-0.41	14	14
AKT	-0.078	0.14	-10000	0	-0.23	210	210
FOXO3	0.011	0	-10000	0	-10000	0	0
AKT1	0.011	0	-10000	0	-10000	0	0
FOXO1	0.008	0.033	-10000	0	-0.42	3	3
AKT3	-0.17	0.21	-10000	0	-0.42	212	212
FOXO4	0.009	0.027	-10000	0	-0.42	2	2
MET	0.005	0.045	-10000	0	-0.34	8	8
PIK3CA	0.01	0.019	-10000	0	-0.42	1	1
PIK3CB	0.011	0	-10000	0	-10000	0	0
NRAS	0.011	0	-10000	0	-10000	0	0
PIK3CG	-0.001	0.069	-10000	0	-0.4	15	15
PIK3R3	0.01	0.012	-10000	0	-0.27	1	1
PIK3R2	0.011	0	-10000	0	-10000	0	0
NF1	0.008	0.033	-10000	0	-0.42	3	3
RAS	-0.021	0.073	0.18	1	-0.25	13	14
ERBB2	0.003	0.044	-10000	0	-0.27	13	13
proliferation/survival/translation	0.016	0.069	0.23	20	-10000	0	20
PI3K	-0.012	0.073	0.15	2	-0.21	24	26
PIK3R1	0.007	0.038	-10000	0	-0.42	4	4
KRAS	0.01	0.012	-10000	0	-0.27	1	1
FOXO	0.021	0.021	-10000	0	-10000	0	0
AKT2	0.011	0	-10000	0	-10000	0	0
PTEN	0.006	0.046	-10000	0	-0.42	6	6

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.032	0.13	-9999	-0.56	4	4
CRP	0.028	0.13	-9999	-0.57	4	4
cell cycle arrest	0.027	0.14	-9999	-0.53	12	12
TIMP1	0.027	0.13	-9999	-0.52	7	7
IL6ST	-0.068	0.17	-9999	-0.41	100	100
Rac1/GDP	-0.009	0.14	-9999	-0.37	42	42
AP1	-0.032	0.13	-9999	-0.47	14	14
GAB2	0.007	0.042	-9999	-0.42	5	5
TNFSF11	0.021	0.14	-9999	-0.54	6	6
HSP90B1	0.032	0.03	-9999	-10000	0	0
GAB1	0.008	0.038	-9999	-0.42	4	4
MAPK14	-0.037	0.15	-9999	-0.42	45	45
AKT1	0.04	0.041	-9999	-0.39	2	2
FOXO1	0.043	0.042	-9999	-0.37	2	2
MAP2K6	-0.041	0.15	-9999	-0.4	50	50
mol:GTP	0.001	0.001	-9999	-10000	0	0
MAP2K4	0.01	0.13	-9999	-0.36	38	38
MITF	-0.043	0.17	-9999	-0.42	62	62
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0.011	0	-9999	-10000	0	0
A2M	0.011	0.08	-9999	-1.3	2	2
CEBPB	0.017	0.001	-9999	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.008	0.092	-9999	-0.55	7	7
STAT3	0.028	0.14	-9999	-0.56	12	12
STAT1	0.002	0.014	-9999	-10000	0	0
CEBPD	0.031	0.14	-9999	-0.59	7	7
PIK3CA	0.011	0.019	-9999	-0.42	1	1
PI3K	0.015	0.03	-9999	-0.28	5	5
JUN	0.006	0.046	-9999	-0.42	6	6
PIAS3/MITF	-0.036	0.16	-9999	-0.39	61	61
MAPK11	-0.038	0.15	-9999	-0.42	45	45
STAT3 (dimer)/FOXO1	0.061	0.13	-9999	-0.48	7	7
GRB2/SOS1/GAB family	-0.051	0.11	-9999	-0.38	38	38
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.031	0.15	-9999	-0.31	75	75
GRB2	0.011	0.001	-9999	-10000	0	0
JAK2	0.003	0.056	-9999	-0.42	9	9
LBP	0.024	0.12	-9999	-0.56	2	2
PIK3R1	0.008	0.038	-9999	-0.42	4	4
JAK1	0.01	0.033	-9999	-0.42	3	3
MYC	0.021	0.18	-9999	-0.94	11	11
FGG	0.027	0.13	-9999	-0.52	7	7
macrophage differentiation	0.027	0.14	-9999	-0.53	12	12
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.048	0.13	-9999	-0.31	66	66
JUNB	0.025	0.15	-9999	-0.69	11	11
FOS	-0.13	0.2	-9999	-0.42	174	174
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.027	0.15	-9999	-0.4	47	47
STAT1/PIAS1	-0.005	0.13	-9999	-0.35	38	38
GRB2/SOS1/GAB family/SHP2/PI3K	0.031	0.043	-9999	-0.29	6	6
STAT3 (dimer)	0.029	0.14	-9999	-0.55	12	12
PRKCD	0.027	0.13	-9999	-0.45	15	15
IL6R	-0.023	0.12	-9999	-0.41	43	43
SOCS3	-0.043	0.17	-9999	-0.71	19	19
gp130 (dimer)/JAK1/JAK1/LMO4	-0.019	0.1	-9999	-0.23	102	102
Rac1/GTP	-0.005	0.14	-9999	-0.37	42	42
HCK	0.01	0.012	-9999	-0.27	1	1
MAPKKK cascade	0.021	0.088	-9999	-0.72	5	5
bone resorption	0.022	0.13	-9999	-0.52	6	6
IRF1	0.032	0.13	-9999	-0.52	6	6
mol:GDP	-0.019	0.14	-9999	-0.39	43	43
SOS1	0.011	0.001	-9999	-10000	0	0
VAV1	-0.019	0.14	-9999	-0.4	43	43
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.054	0.19	-9999	-0.53	50	50
PTPN11	0.002	0.014	-9999	-10000	0	0
IL6/IL6RA	-0.018	0.11	-9999	-0.29	65	65
gp130 (dimer)/TYK2/TYK2/LMO4	-0.021	0.1	-9999	-0.23	100	100
gp130 (dimer)/JAK2/JAK2/LMO4	-0.026	0.11	-9999	-0.23	106	106
IL6	-0.007	0.09	-9999	-0.37	29	29
PIAS3	0.011	0	-9999	-10000	0	0
PTPRE	0.002	0.023	-9999	-0.35	2	2
PIAS1	0.011	0	-9999	-10000	0	0
RAC1	0.011	0.001	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.04	0.14	-9999	-0.26	125	125
LMO4	0.015	0.005	-9999	-10000	0	0
STAT3 (dimer)/PIAS3	0.025	0.14	-9999	-0.55	12	12
MCL1	0.044	0.038	-9999	-0.36	1	1

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.086	0.11	-9999	-0.2	219	219
TC10/GTP	-0.066	0.081	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	0.002	0.068	-9999	-0.21	47	47
HRAS	0.011	0	-9999	-10000	0	0
APS homodimer	0.011	0	-9999	-10000	0	0
GRB14	-0.089	0.14	-9999	-0.27	179	179
FOXO3	0.004	0.047	-9999	-0.55	3	3
AKT1	-0.02	0.079	-9999	-0.26	22	22
INSR	0.012	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0.029	0.001	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.01	0.019	-9999	-0.42	1	1
SORBS1	-0.16	0.21	-9999	-0.42	206	206
CRK	0.011	0	-9999	-10000	0	0
PTPN1	0.026	0.001	-9999	-10000	0	0
CAV1	-0.046	0.12	-9999	-0.23	135	135
CBL/APS/CAP/Crk-II/C3G	-0.055	0.11	-9999	-0.18	206	206
Insulin Receptor/Insulin/IRS1/NCK2	0.002	0.068	-9999	-0.21	47	47
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.018	0.057	-9999	-0.19	50	50
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.013	0.053	-9999	-10000	0	0
RPS6KB1	-0.013	0.075	-9999	-0.24	22	22
PARD6A	0.011	0	-9999	-10000	0	0
CBL	0.011	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0.003	-9999	-10000	0	0
PIK3R1	0.007	0.038	-9999	-0.42	4	4
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.036	0.057	-9999	-0.24	22	22
HRAS/GTP	-0.014	0.043	-9999	-10000	0	0
Insulin Receptor	0.012	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.008	0.063	-9999	-0.19	47	47
PRKCI	-0.009	0.016	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.047	0.069	-9999	-0.28	22	22
SHC1	0.011	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	-0.003	0.029	-9999	-0.4	2	2
PI3K	-0.018	0.057	-9999	-0.19	50	50
NCK2	0.011	0	-9999	-10000	0	0
RHOQ	0.011	0	-9999	-10000	0	0
mol:H2O2	0	0	-9999	-10000	0	0
HRAS/GDP	0.008	0	-9999	-10000	0	0
AKT2	-0.02	0.079	-9999	-0.26	22	22
PRKCZ	-0.009	0.027	-9999	-0.5	1	1
SH2B2	0.011	0	-9999	-10000	0	0
SHC/SHIP	0.007	0.06	-9999	-0.18	48	48
F2RL2	-0.015	0.1	-9999	-0.4	32	32
TRIP10	0.011	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	0.016	0.001	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.014	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.028	0.001	-9999	-10000	0	0
RAPGEF1	0.011	0	-9999	-10000	0	0
RASA1	0.006	0.042	-9999	-0.42	5	5
NCK1	0.009	0.027	-9999	-0.42	2	2
CBL/APS/CAP/Crk-II	-0.065	0.11	-9999	-0.2	206	206
TC10/GDP	0.008	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.023	0.011	-9999	-0.21	1	1
INPP5D	0.001	0.063	-9999	-0.2	48	48
SOS1	0.011	0	-9999	-10000	0	0
SGK1	-0.007	0.061	-9999	-0.8	3	3
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.011	0	-9999	-10000	0	0
IRS1	-0.029	0.12	-9999	-0.42	47	47
p62DOK/RasGAP	0.017	0.031	-9999	-0.4	2	2
INS	0.003	0.002	-9999	-10000	0	0
mol:PI-3-4-P2	0.001	0.063	-9999	-0.2	48	48
GRB2	0.011	0	-9999	-10000	0	0
EIF4EBP1	-0.016	0.078	-9999	-0.25	24	24
PTPRA	0.012	0	-9999	-10000	0	0
PIK3CA	0.01	0.019	-9999	-0.42	1	1
TC10/GTP/CIP4	0.014	0	-9999	-10000	0	0
PDPK1	0.011	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.006	0.063	-9999	-0.19	47	47
Insulin Receptor/Insulin/IRS1	-0.005	0.068	-9999	-0.22	47	47
Insulin Receptor/Insulin/IRS3	0.011	0.002	-9999	-10000	0	0
Par3/Par6	0.012	0.051	-9999	-0.19	29	29

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.009	0.033	-9999	-0.42	3	3
SVIL	-0.042	0.14	-9999	-0.42	64	64
ZNF318	0.01	0.004	-9999	-10000	0	0
JMJD2C	0	0.022	-9999	-0.13	14	14
T-DHT/AR/Ubc9	-0.027	0.1	-9999	-0.24	92	92
CARM1	0.011	0	-9999	-10000	0	0
PRDX1	0.011	0	-9999	-10000	0	0
PELP1	0.01	0.001	-9999	-10000	0	0
CTNNB1	0.011	0.001	-9999	-10000	0	0
AKT1	0.01	0.001	-9999	-10000	0	0
PTK2B	0.011	0.001	-9999	-10000	0	0
MED1	0.01	0.001	-9999	-10000	0	0
MAK	-0.01	0.073	-9999	-0.27	36	36
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	0.007	0.042	-9999	-0.42	5	5
GSN	0.004	0.053	-9999	-0.42	8	8
NCOA2	-0.004	0.079	-9999	-0.42	18	18
NCOA6	0.011	0.002	-9999	-10000	0	0
DNA-PK	0.021	0.004	-9999	-10000	0	0
NCOA4	0.011	0	-9999	-10000	0	0
PIAS3	0.011	0.001	-9999	-10000	0	0
cell proliferation	-0.008	0.024	-9999	-10000	0	0
XRCC5	0.01	0.001	-9999	-10000	0	0
UBE3A	0.011	0.002	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.047	0.12	-9999	-0.25	124	124
FHL2	-0.009	0.14	-9999	-0.92	10	10
RANBP9	0.011	0.002	-9999	-10000	0	0
JMJD1A	0.004	0.03	-9999	-0.13	22	22
CDK6	0.003	0.056	-9999	-0.42	9	9
TGFB1I1	-0.12	0.2	-9999	-0.42	151	151
T-DHT/AR/CyclinD1	-0.027	0.11	-9999	-0.25	90	90
XRCC6	0.01	0.001	-9999	-10000	0	0
T-DHT/AR	-0.022	0.12	-9999	-0.26	97	97
CTDSP1	0.011	0	-9999	-10000	0	0
CTDSP2	0.01	0.002	-9999	-10000	0	0
BRCA1	0.011	0.002	-9999	-10000	0	0
TCF4	-0.006	0.081	-9999	-0.42	19	19
CDKN2A	-0.11	0.14	-9999	-0.27	224	224
SRF	0.014	0.018	-9999	-10000	0	0
NKX3-1	-0.025	0.18	-9999	-0.79	21	21
KLK3	-0.005	0.036	-9999	-10000	0	0
TMF1	0.011	0	-9999	-10000	0	0
HNRNPA1	0.01	0.001	-9999	-10000	0	0
AOF2	0.001	0.002	-9999	-10000	0	0
APPL1	0.017	0.002	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.028	0.1	-9999	-0.24	92	92
AR	-0.064	0.17	-9999	-0.42	90	90
UBA3	0.011	0	-9999	-10000	0	0
PATZ1	0.01	0.001	-9999	-10000	0	0
PAWR	0.011	0	-9999	-10000	0	0
PRKDC	0.01	0.001	-9999	-10000	0	0
PA2G4	0.01	0.001	-9999	-10000	0	0
UBE2I	0.011	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.024	0.096	-9999	-0.22	92	92
RPS6KA3	0.01	0.019	-9999	-0.42	1	1
T-DHT/AR/ARA70	-0.027	0.11	-9999	-0.24	92	92
LATS2	0.008	0.033	-9999	-0.42	3	3
T-DHT/AR/PRX1	-0.024	0.095	-9999	-0.22	90	90
Cyclin D3/CDK11 p58	0.008	0	-9999	-10000	0	0
VAV3	-0.06	0.12	-9999	-0.27	129	129
KLK2	-0.045	0.15	-9999	-0.89	14	14
CASP8	0.01	0	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.024	0.11	-9999	-0.23	102	102
TMPRSS2	-0.019	0.14	-9999	-0.68	15	15
CCND1	0.011	0	-9999	-10000	0	0
PIAS1	0.011	0.002	-9999	-10000	0	0
mol:T-DHT	0	0.019	-9999	-0.068	29	29
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.012	0.003	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.032	0.11	-9999	-0.25	99	99
CMTM2	0.008	0.022	-9999	-0.27	3	3
SNURF	-0.022	0.11	-9999	-0.41	36	36
ZMIZ1	0.009	0.038	-9999	-0.43	3	3
CCND3	0.011	0	-9999	-10000	0	0
TGIF1	0.01	0.001	-9999	-10000	0	0
FKBP4	0.011	0.002	-9999	-10000	0	0

×

Visual signal transduction: Cones

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.004	0.055	-9999	-0.21	31	31
RGS9BP	-0.004	0.06	-9999	-0.27	24	24
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0.002	0.013	-9999	-0.27	1	1
mol:Na +	-0.007	0.058	-9999	-0.24	30	30
mol:ADP	0.007	0.013	-9999	-0.18	2	2
GNAT2	0.007	0.022	-9999	-0.27	3	3
RGS9-1/Gbeta5/R9AP	-0.043	0.11	-9999	-0.24	115	115
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0.007	0.013	-9999	-0.15	3	3
GRK7	0.006	0.013	-9999	-0.27	1	1
CNGB3	-0.019	0.098	-9999	-0.42	29	29
Cone Metarhodopsin II/X-Arrestin	0.002	0.009	-9999	-0.18	1	1
mol:Ca2+	-0.004	0.052	-9999	-0.22	29	29
Cone PDE6	-0.033	0.093	-9999	-0.2	115	115
Cone Metarhodopsin II	0.006	0.01	-9999	-0.13	2	2
Na + (4 Units)	-0.003	0.052	-9999	-0.22	29	29
GNAT2/GDP	-0.032	0.093	-9999	-0.2	115	115
GNB5	0.011	0	-9999	-10000	0	0
mol:GMP (4 units)	0.008	0.012	-9999	-10000	0	0
Cone Transducin	0.004	0.059	-9999	-0.22	31	31
SLC24A2	0.004	0.005	-9999	-10000	0	0
GNB3/GNGT2	-0.003	0.075	-9999	-0.29	31	31
GNB3	-0.014	0.099	-9999	-0.42	29	29
GNAT2/GTP	0.006	0.015	-9999	-0.18	3	3
CNGA3	0.006	0.013	-9999	-0.27	1	1
ARR3	0.003	0.013	-9999	-0.27	1	1
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.007	0.058	-9999	-0.24	30	30
mol:Pi	-0.043	0.11	-9999	-0.24	115	115
Cone CNG Channel	-0.011	0.044	-9999	-0.19	29	29
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	0.004	0.005	-9999	-10000	0	0
RGS9	-0.085	0.18	-9999	-0.42	115	115
PDE6C	0.004	0.005	-9999	-10000	0	0
GNGT2	0.008	0.033	-9999	-0.42	3	3
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.002	0.004	-9999	-10000	0	0

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	0.01	0.012	-9999	-0.27	1	1
GPC2	-0.006	0.067	-9999	-0.27	31	31
GPC2/Midkine	0.004	0.046	-9999	-0.18	32	32
neuron projection morphogenesis	0.004	0.046	-9999	-0.17	32	32

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.01	0.042	-9999	-0.24	12	12
NFATC2	-0.009	0.078	-9999	-0.24	50	50
NFATC3	0.016	0.016	-9999	-10000	0	0
CD40LG	-0.053	0.17	-9999	-0.45	48	48
PTGS2	-0.076	0.21	-9999	-0.48	80	80
JUNB	0.006	0.042	-9999	-0.42	5	5
CaM/Ca2+/Calcineurin A alpha-beta B1	0	0.008	-9999	-10000	0	0
CaM/Ca2+	0	0.008	-9999	-10000	0	0
CALM1	0.011	0.004	-9999	-10000	0	0
JUN	0.006	0.046	-9999	-0.42	6	6
mol:Ca2+	-0.002	0.006	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.005	0.004	-9999	-10000	0	0
FOSL1	-0.008	0.07	-9999	-0.27	34	34
CREM	0.01	0	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.026	0.08	-9999	-0.28	23	23
FOS	-0.13	0.2	-9999	-0.42	174	174
IFNG	-0.057	0.18	-9999	-0.47	44	44
AP-1/NFAT1-c-4	-0.06	0.19	-9999	-0.47	57	57
FASLG	-0.052	0.17	-9999	-0.47	39	39
NFAT1-c-4/ICER1	-0.007	0.078	-9999	-0.26	19	19
IL2RA	-0.053	0.17	-9999	-0.44	49	49
FKBP12/FK506	0.008	0	-9999	-10000	0	0
CSF2	-0.053	0.17	-9999	-0.43	46	46
JunB/Fra1/NFAT1-c-4	-0.011	0.081	-9999	-0.25	24	24
IL4	-0.053	0.16	-9999	-0.45	41	41
IL2	-0.008	0.021	-9999	-10000	0	0
IL3	-0.011	0.015	-9999	-10000	0	0
FKBP1A	0.011	0	-9999	-10000	0	0
BATF3	0.01	0.012	-9999	-0.27	1	1
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.011	0	-9999	-10000	0	0

×

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

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
MET/RANBP9	0.012	0.031	-10000	0	-0.23	8	8
CRKL	-0.012	0.095	-10000	0	-0.42	10	10
mol:PIP3	-0.009	0.044	0.39	6	-10000	0	6
AKT1	0.005	0.031	0.28	6	-10000	0	6
PTK2B	0.011	0	-10000	0	-10000	0	0
RAPGEF1	-0.006	0.091	-10000	0	-0.41	9	9
RANBP10	0.011	0	-10000	0	-10000	0	0
PIK3CA	0.01	0.019	-10000	0	-0.42	1	1
HGF/MET/SHIP2	-0.029	0.1	-10000	0	-0.24	97	97
MAP3K5	0.001	0.089	-10000	0	-0.4	10	10
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.019	0.095	-10000	0	-0.21	97	97
AP1	-0.077	0.13	-10000	0	-0.26	174	174
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.011	0	-10000	0	-10000	0	0
apoptosis	-0.23	0.35	-10000	0	-0.71	174	174
STAT3 (dimer)	-0.013	0.095	-10000	0	-0.4	5	5
GAB1/CRKL/SHP2/PI3K	-0.032	0.077	-10000	0	-0.41	11	11
INPP5D	0.01	0.019	-10000	0	-0.42	1	1
CBL/CRK	-0.005	0.091	-10000	0	-0.47	7	7
PTPN11	0.011	0	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.011	0	-10000	0	-10000	0	0
PTEN	0.006	0.046	-10000	0	-0.42	6	6
ELK1	-0.003	0.018	-10000	0	-0.16	4	4
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.024	0.052	-10000	0	-0.27	5	5
PAK1	0.01	0.029	0.27	6	-10000	0	6
HGF/MET/RANBP10	-0.029	0.1	-10000	0	-0.24	97	97
HRAS	-0.022	0.12	-10000	0	-0.68	4	4
DOCK1	-0.008	0.097	-10000	0	-0.44	11	11
GAB1	-0.018	0.1	-10000	0	-0.44	10	10
CRK	-0.012	0.095	-10000	0	-0.44	9	9
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.08	0.17	-10000	0	-0.42	97	97
JUN	0.006	0.046	-10000	0	-0.42	6	6
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.023	0.074	-10000	0	-0.17	97	97
PIK3R1	0.007	0.038	-10000	0	-0.42	4	4
cell morphogenesis	0.001	0.11	-10000	0	-0.41	10	10
GRB2/SHC	-0.008	0.066	-10000	0	-0.27	5	5
FOS	-0.13	0.2	-10000	0	-0.42	174	174
GLMN	0	0	-10000	0	-10000	0	0
cell motility	-0.003	0.018	-10000	0	-0.16	4	4
HGF/MET/MUC20	-0.036	0.1	-10000	0	-0.24	101	101
cell migration	-0.008	0.065	-10000	0	-0.27	5	5
GRB2	0.011	0	-10000	0	-10000	0	0
CBL	0.011	0	-10000	0	-10000	0	0
MET/RANBP10	0.012	0.031	-10000	0	-0.23	8	8
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.017	0.094	-10000	0	-0.2	100	100
MET/MUC20	0.004	0.031	-10000	0	-0.24	8	8
RAP1B	0	0.086	-10000	0	-0.43	7	7
RAP1A	0	0.086	-10000	0	-0.43	7	7
HGF/MET/RANBP9	-0.029	0.1	-10000	0	-0.24	97	97
RAF1	-0.015	0.11	-10000	0	-0.64	4	4
STAT3	-0.014	0.096	-10000	0	-0.2	100	100
cell proliferation	-0.021	0.13	-10000	0	-0.28	97	97
RPS6KB1	-0.002	0.028	-10000	0	-0.14	3	3
MAPK3	-0.007	0.016	-10000	0	-10000	0	0
MAPK1	-0.007	0.016	-10000	0	-10000	0	0
RANBP9	0.011	0	-10000	0	-10000	0	0
MAPK8	0.012	0.095	-10000	0	-0.42	12	12
SRC	-0.01	0.089	-10000	0	-0.38	5	5
PI3K	-0.01	0.072	-10000	0	-0.3	9	9
MET/Glomulin	0.007	0.027	-10000	0	-0.2	8	8
SOS1	0.011	0	-10000	0	-10000	0	0
MAP2K1	-0.009	0.1	-10000	0	-0.58	4	4
MET	0.005	0.045	-10000	0	-0.34	8	8
MAP4K1	-0.003	0.091	-10000	0	-0.46	7	7
PTK2	0.011	0	-10000	0	-10000	0	0
MAP2K2	-0.009	0.1	-10000	0	-0.58	4	4
BAD	0.01	0.029	0.27	6	-10000	0	6
MAP2K4	0.007	0.083	-10000	0	-0.36	10	10
SHP2/GRB2/SOS1/GAB1	-0.031	0.076	-10000	0	-0.44	8	8
INPPL1	0.011	0	-10000	0	-10000	0	0
PXN	0.011	0	-10000	0	-10000	0	0
SH3KBP1	0.011	0	-10000	0	-10000	0	0
HGS	-0.015	0.068	-10000	0	-0.29	5	5
PLCgamma1/PKC	0.008	0	-10000	0	-10000	0	0
HGF	-0.069	0.17	-10000	0	-0.42	96	96
RASA1	0.006	0.042	-10000	0	-0.42	5	5
NCK1	0.009	0.027	-10000	0	-0.42	2	2
PTPRJ	0.01	0.018	-10000	0	-0.27	2	2
NCK/PLCgamma1	-0.01	0.075	-10000	0	-0.28	7	7
PDPK1	-0.001	0.035	0.32	6	-10000	0	6
HGF/MET/SHIP	-0.03	0.1	-10000	0	-0.24	98	98

×

Glucocorticoid receptor regulatory network

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
PCK2	-0.015	0.041	0.22	1	-10000	0	1
SMARCC2	0.012	0.003	-10000	0	-10000	0	0
SMARCC1	0.012	0.004	-10000	0	-10000	0	0
TBX21	0.028	0.088	-10000	0	-0.49	6	6
SUMO2	0.009	0.005	-10000	0	-10000	0	0
STAT1 (dimer)	0.016	0.012	-10000	0	-0.26	1	1
FKBP4	0.011	0	-10000	0	-10000	0	0
FKBP5	0.001	0.062	-10000	0	-0.42	11	11
GR alpha/HSP90/FKBP51/HSP90	-0.019	0.11	0.22	6	-0.26	65	71
PRL	-0.03	0.28	-10000	0	-1.2	24	24
cortisol/GR alpha (dimer)/TIF2	-0.008	0.15	0.42	16	-0.38	8	24
RELA	-0.015	0.069	-10000	0	-0.23	11	11
FGG	-0.02	0.13	0.35	12	-0.31	17	29
GR beta/TIF2	-0.036	0.13	0.23	6	-0.3	81	87
IFNG	-0.06	0.12	-10000	0	-0.56	3	3
apoptosis	-0.1	0.2	0.46	10	-0.5	60	70
CREB1	0.01	0.015	-10000	0	-10000	0	0
histone acetylation	0.04	0.073	0.35	3	-0.25	5	8
BGLAP	0.038	0.062	-10000	0	-10000	0	0
GR/PKAc	-0.012	0.096	0.22	4	-0.23	61	65
NF kappa B1 p50/RelA	-0.025	0.12	-10000	0	-0.28	81	81
SMARCD1	0.012	0.004	-10000	0	-10000	0	0
MDM2	0.015	0.038	0.17	10	-10000	0	10
GATA3	0.001	0.064	-10000	0	-0.3	22	22
AKT1	0.005	0.001	-10000	0	-10000	0	0
CSF2	0.025	0.062	-10000	0	-10000	0	0
GSK3B	0.009	0.005	-10000	0	-10000	0	0
NR1I3	-0.075	0.19	0.46	8	-0.52	29	37
CSN2	-0.019	0.11	0.32	6	-0.29	9	15
BRG1/BAF155/BAF170/BAF60A	0.033	0.011	-10000	0	-10000	0	0
NFATC1	0.003	0.065	-10000	0	-0.41	12	12
POU2F1	0.004	0.052	-10000	0	-0.23	23	23
CDKN1A	0.027	0.1	-10000	0	-1.3	3	3
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.001	0.007	-10000	0	-10000	0	0
SFN	-0.21	0.12	-10000	0	-0.27	400	400
GR alpha/HSP90/FKBP51/HSP90/14-3-3	-0.096	0.15	0.22	16	-0.32	91	107
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.14	0.32	0.44	9	-0.8	88	97
JUN	-0.011	0.083	-10000	0	-0.37	8	8
IL4	0.022	0.075	-10000	0	-10000	0	0
CDK5R1	0.009	0.013	-10000	0	-0.27	1	1
PRKACA	0.011	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.18	0.16	-10000	0	-0.36	174	174
GR alpha/HSP90/FKBP51/HSP90/PP5C	-0.01	0.1	0.22	5	-0.23	62	67
cortisol/GR alpha (monomer)	-0.01	0.17	0.48	15	-0.36	21	36
NCOA2	-0.004	0.079	-10000	0	-0.42	18	18
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.16	0.2	-10000	0	-0.44	174	174
AP-1/NFAT1-c-4	-0.12	0.16	-10000	0	-0.47	29	29
AFP	0.006	0.067	-10000	0	-0.48	2	2
SUV420H1	0.011	0	-10000	0	-10000	0	0
IRF1	0.007	0.087	0.37	2	-10000	0	2
TP53	0.024	0.042	-10000	0	-0.45	4	4
PPP5C	0.011	0	-10000	0	-10000	0	0
KRT17	-0.081	0.15	-10000	0	-0.65	10	10
KRT14	-0.015	0.11	0.42	1	-1.2	2	3
TBP	0.018	0	-10000	0	-10000	0	0
CREBBP	0.019	0.039	0.3	2	-0.28	4	6
HDAC1	0.01	0.002	-10000	0	-10000	0	0
HDAC2	0.01	0.001	-10000	0	-10000	0	0
AP-1	-0.12	0.16	-10000	0	-0.47	29	29
MAPK14	0.009	0.006	-10000	0	-10000	0	0
MAPK10	-0.086	0.18	-10000	0	-0.42	115	115
MAPK11	0.008	0.027	-10000	0	-0.42	2	2
KRT5	-0.097	0.14	-10000	0	-0.68	6	6
interleukin-1 receptor activity	-0.001	0.001	-10000	0	-10000	0	0
NCOA1	0.011	0.019	-10000	0	-0.41	1	1
STAT1	0.016	0.012	-10000	0	-0.27	1	1
CGA	0.023	0.07	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	-0.016	0.098	0.29	4	-0.44	4	8
MAPK3	0.009	0.006	-10000	0	-10000	0	0
MAPK1	0.009	0.006	-10000	0	-10000	0	0
ICAM1	0	0.12	-10000	0	-0.39	10	10
NFKB1	-0.016	0.071	-10000	0	-0.2	29	29
MAPK8	0.01	0.086	0.25	1	-0.32	8	9
MAPK9	0.009	0.006	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.11	0.21	0.46	10	-0.52	63	73
BAX	0.033	0.034	-10000	0	-10000	0	0
POMC	-0.04	0.23	-10000	0	-1.3	11	11
EP300	0.02	0.033	0.3	2	-0.23	3	5
cortisol/GR alpha (dimer)/p53	0.009	0.15	0.44	15	-0.37	2	17
proteasomal ubiquitin-dependent protein catabolic process	0.006	0.03	0.16	3	-10000	0	3
SGK1	0.027	0.11	-10000	0	-1.3	3	3
IL13	-0.036	0.1	-10000	0	-0.62	1	1
IL6	-0.029	0.22	-10000	0	-0.89	23	23
PRKACG	0.003	0.005	-10000	0	-10000	0	0
IL5	-0.036	0.089	-10000	0	-0.54	1	1
IL2	-0.062	0.12	-10000	0	-0.5	4	4
CDK5	0.01	0.004	-10000	0	-10000	0	0
PRKACB	0.006	0.046	-10000	0	-0.42	6	6
HSP90AA1	0.011	0	-10000	0	-10000	0	0
IL8	-0.017	0.12	-10000	0	-0.39	13	13
CDK5R1/CDK5	0.013	0.012	-10000	0	-0.18	1	1
NF kappa B1 p50/RelA/PKAc	0.001	0.096	-10000	0	-0.31	16	16
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.01	0.13	0.39	18	-0.34	2	20
SMARCA4	0.012	0.003	-10000	0	-10000	0	0
chromatin remodeling	0.004	0.11	0.3	8	-0.48	4	12
NF kappa B1 p50/RelA/Cbp	0.011	0.11	0.39	1	-0.34	15	16
JUN (dimer)	-0.011	0.083	-10000	0	-0.36	8	8
YWHAH	0.011	0	-10000	0	-10000	0	0
VIPR1	0.03	0.084	-10000	0	-0.61	3	3
NR3C1	-0.044	0.17	0.3	10	-0.4	80	90
NR4A1	-0.089	0.19	-10000	0	-0.42	121	121
TIF2/SUV420H1	0.005	0.055	-10000	0	-0.29	18	18
MAPKKK cascade	-0.1	0.2	0.46	10	-0.5	60	70
cortisol/GR alpha (dimer)/Src-1	0.005	0.15	0.41	18	-0.35	3	21
PBX1	-0.014	0.1	-10000	0	-0.34	42	42
POU1F1	-0.006	0.055	-10000	0	-0.25	24	24
SELE	-0.11	0.35	-10000	0	-0.93	78	78
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.004	0.11	0.3	8	-0.49	4	12
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.01	0.13	0.39	18	-0.34	2	20
mol:cortisol	0.009	0.069	0.26	15	-10000	0	15
MMP1	-0.069	0.083	-10000	0	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.047	0.12	-9999	-0.28	107	107
AKT1	0.018	0.15	-9999	-0.52	30	30
PTK2B	-0.027	0.15	-9999	-0.56	28	28
VEGFR2 homodimer/Frs2	-0.005	0.14	-9999	-0.57	28	28
CAV1	-0.082	0.18	-9999	-0.42	111	111
CALM1	0.011	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.005	0.13	-9999	-0.52	28	28
endothelial cell proliferation	0.014	0.15	-9999	-0.46	37	37
mol:Ca2+	-0.003	0.14	-9999	-0.56	28	28
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.011	0.12	-9999	-0.49	28	28
RP11-342D11.1	-0.01	0.14	-9999	-0.57	28	28
CDH5	0.005	0.05	-9999	-0.42	7	7
VEGFA homodimer	0.028	0.01	-9999	-0.2	1	1
SHC1	0.011	0	-9999	-10000	0	0
SHC2	-0.048	0.15	-9999	-0.42	70	70
HRAS/GDP	-0.034	0.11	-9999	-0.48	28	28
SH2D2A	0.001	0.052	-9999	-0.27	18	18
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.034	0.11	-9999	-0.48	28	28
VEGFR2 homodimer/VEGFA homodimer/TsAd	0	0.13	-9999	-0.53	28	28
VEGFR1 homodimer	0.01	0.019	-9999	-0.42	1	1
SHC/GRB2/SOS1	-0.038	0.13	-9999	-0.53	28	28
GRB10	-0.003	0.15	-9999	-0.57	28	28
PTPN11	0.011	0	-9999	-10000	0	0
GRB2	0.011	0	-9999	-10000	0	0
PAK1	0.011	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.013	0.13	-9999	-0.52	28	28
HRAS	0.011	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	-0.018	0.12	-9999	-0.39	28	28
HIF1A	0.011	0	-9999	-10000	0	0
FRS2	0.011	0	-9999	-10000	0	0
oxygen and reactive oxygen species metabolic process	0.01	0.12	-9999	-0.49	28	28
mol:GTP	0	0	-9999	-10000	0	0
FLT4	-0.007	0.085	-9999	-0.42	21	21
Nck/Pak	0.015	0.019	-9999	-0.29	2	2
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.005	0.13	-9999	-0.52	28	28
mol:GDP	-0.037	0.12	-9999	-0.52	28	28
mol:NADP	0.022	0.12	-9999	-0.41	28	28
eNOS/Hsp90	0.026	0.11	-9999	-0.39	28	28
PIK3R1	0.007	0.038	-9999	-0.42	4	4
mol:IP3	-0.003	0.15	-9999	-0.57	28	28
HIF1A/ARNT	0.016	0	-9999	-10000	0	0
SHB	0.011	0	-9999	-10000	0	0
VEGFA	0.012	0.001	-9999	-10000	0	0
VEGFC	0.004	0.053	-9999	-0.42	8	8
FAK1/Vinculin	-0.014	0.16	-9999	-0.61	28	28
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.011	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.032	0.16	-9999	-0.6	28	28
PTPN6	0.01	0.012	-9999	-0.27	1	1
EPAS1	-0.001	0.084	-9999	-0.33	29	29
mol:L-citrulline	0.022	0.12	-9999	-0.41	28	28
ITGAV	0.011	0	-9999	-10000	0	0
PIK3CA	0.01	0.019	-9999	-0.42	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.011	0.12	-9999	-0.49	28	28
VEGFR2 homodimer/VEGFA homodimer	-0.01	0.16	-9999	-0.62	28	28
VEGFR2/3 heterodimer	-0.015	0.15	-9999	-0.45	46	46
VEGFB	0.011	0	-9999	-10000	0	0
MAPK11	-0.005	0.16	-9999	-0.58	29	29
VEGFR2 homodimer	-0.01	0.16	-9999	-0.64	29	29
FLT1	0.01	0.019	-9999	-0.42	1	1
NEDD4	-0.024	0.12	-9999	-0.41	44	44
MAPK3	-0.008	0.14	-9999	-0.47	36	36
MAPK1	-0.008	0.14	-9999	-0.47	36	36
VEGFA145/NRP2	0.002	0.066	-9999	-0.28	26	26
VEGFR1/2 heterodimer	-0.005	0.14	-9999	-0.58	28	28
KDR	-0.01	0.16	-9999	-0.65	29	29
VEGFA165/NRP1/VEGFR2 homodimer	-0.013	0.16	-9999	-0.57	31	31
SRC	0.011	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	-0.008	0.15	-9999	-0.48	36	36
PI3K	0.008	0.16	-9999	-0.59	30	30
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.004	0.13	-9999	-0.53	28	28
FES	-0.004	0.15	-9999	-0.57	29	29
GAB1	-0.039	0.14	-9999	-0.62	28	28
VEGFR2 homodimer/VEGFA homodimer/Src	0.005	0.13	-9999	-0.52	28	28
CTNNB1	0.011	0	-9999	-10000	0	0
SOS1	0.011	0	-9999	-10000	0	0
ARNT	0.011	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.007	0.14	-9999	-0.42	41	41
VEGFR2 homodimer/VEGFA homodimer/Yes	0.005	0.13	-9999	-0.52	28	28
PI3K/GAB1	0.019	0.15	-9999	-0.54	30	30
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.015	0.12	-9999	-0.48	28	28
PRKACA	0.011	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.01	0.14	-9999	-0.57	28	28
HSP90AA1	0.011	0	-9999	-10000	0	0
CDC42	-0.004	0.15	-9999	-0.58	28	28
actin cytoskeleton reorganization	0	0.13	-9999	-0.52	28	28
PTK2	-0.021	0.17	-9999	-0.66	28	28
EDG1	-0.01	0.14	-9999	-0.57	28	28
mol:DAG	-0.003	0.15	-9999	-0.57	28	28
CaM/Ca2+	0.002	0.14	-9999	-0.52	28	28
MAP2K3	0	0.14	-9999	-0.55	28	28
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.003	0.15	-9999	-0.59	28	28
PLCG1	-0.004	0.15	-9999	-0.58	28	28
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.011	0.12	-9999	-0.49	28	28
IQGAP1	0.011	0	-9999	-10000	0	0
YES1	0.011	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.005	0.13	-9999	-0.52	28	28
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.005	0.13	-9999	-0.52	28	28
cell migration	0.008	0.15	-9999	-0.54	28	28
mol:PI-3-4-5-P3	0.01	0.15	-9999	-0.54	30	30
FYN	0.011	0	-9999	-10000	0	0
VEGFB/NRP1	-0.003	0.14	-9999	-0.53	28	28
mol:NO	0.022	0.12	-9999	-0.41	28	28
PXN	0.011	0	-9999	-10000	0	0
HRAS/GTP	-0.034	0.11	-9999	-0.48	28	28
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.003	0.15	-9999	-0.59	28	28
VHL	0.01	0.019	-9999	-0.42	1	1
ITGB3	-0.078	0.17	-9999	-0.41	107	107
NOS3	0.02	0.13	-9999	-0.47	28	28
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.026	0.15	-9999	-0.55	28	28
RAC1	0.011	0	-9999	-10000	0	0
PRKCA	-0.01	0.15	-9999	-0.52	33	33
PRKCB	-0.009	0.15	-9999	-0.52	33	33
VCL	0.011	0	-9999	-10000	0	0
VEGFA165/NRP1	-0.009	0.14	-9999	-0.57	28	28
VEGFR1/2 heterodimer/VEGFA homodimer	0.004	0.13	-9999	-0.53	28	28
VEGFA165/NRP2	0.002	0.066	-9999	-0.28	26	26
MAPKKK cascade	0.018	0.13	-9999	-0.48	28	28
NRP2	-0.011	0.094	-9999	-0.42	26	26
VEGFC homodimer	0.004	0.053	-9999	-0.42	8	8
NCK1	0.009	0.027	-9999	-0.42	2	2
ROCK1	0.011	0	-9999	-10000	0	0
FAK1/Paxillin	-0.014	0.16	-9999	-0.61	28	28
MAP3K13	-0.006	0.15	-9999	-0.58	28	28
PDPK1	0.017	0.14	-9999	-0.48	30	30

×

IL2 signaling events mediated by STAT5

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.007	0.042	-9999	-0.42	5	5
ELF1	0.01	0.044	-9999	-0.39	5	5
CCNA2	-0.069	0.13	-9999	-0.27	144	144
PIK3CA	0.01	0.019	-9999	-0.42	1	1
JAK3	0.01	0.022	-9999	-0.27	3	3
PIK3R1	0.008	0.038	-9999	-0.42	4	4
JAK1	0.009	0.033	-9999	-0.42	3	3
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.052	0.044	-9999	-0.51	1	1
SHC1	0.011	0	-9999	-10000	0	0
SP1	-0.041	0.12	-9999	-0.31	92	92
IL2RA	0.015	0.051	-9999	-0.35	5	5
IL2RB	0.01	0.019	-9999	-0.42	1	1
SOS1	0.011	0	-9999	-10000	0	0
IL2RG	0.007	0.038	-9999	-0.31	7	7
G1/S transition of mitotic cell cycle	-0.094	0.26	-9999	-0.64	92	92
PTPN11	0.011	0	-9999	-10000	0	0
CCND2	-0.098	0.26	-9999	-0.66	92	92
LCK	0.008	0.031	-9999	-0.3	5	5
GRB2	0.011	0	-9999	-10000	0	0
IL2	-0.004	0.05	-9999	-0.27	17	17
CDK6	0.003	0.056	-9999	-0.42	9	9
CCND3	0.055	0.04	-9999	-0.44	1	1

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	0.015	0.08	-10000	0	-0.3	24	24
IKBKB	0.028	0.045	0.16	1	-0.18	1	2
AKT1	0.007	0.061	0.18	5	-0.19	22	27
IKBKG	0.03	0.046	0.16	1	-0.18	1	2
CALM1	0.023	0.075	0.17	62	-0.25	16	78
PIK3CA	0.01	0.019	-10000	0	-0.42	1	1
MAP3K1	0.005	0.1	-10000	0	-0.41	24	24
MAP3K7	0.011	0	-10000	0	-10000	0	0
mol:Ca2+	0.018	0.079	0.18	62	-0.26	16	78
DOK1	0.011	0	-10000	0	-10000	0	0
AP-1	-0.004	0.075	0.14	35	-0.19	24	59
LYN	0.011	0	-10000	0	-10000	0	0
BLNK	0.009	0.023	-10000	0	-0.34	2	2
SHC1	0.011	0	-10000	0	-10000	0	0
BCR complex	-0.018	0.084	-10000	0	-0.21	75	75
CD22	-0.054	0.12	-10000	0	-0.47	29	29
CAMK2G	0.028	0.072	0.17	62	-0.23	16	78
CSNK2A1	0.011	0	-10000	0	-10000	0	0
INPP5D	0.01	0.019	-10000	0	-0.42	1	1
SHC/GRB2/SOS1	-0.015	0.04	-10000	0	-0.33	1	1
GO:0007205	0.018	0.079	0.18	62	-0.27	16	78
SYK	0.01	0.012	-10000	0	-0.27	1	1
ELK1	0.023	0.076	0.17	62	-0.25	16	78
NFATC1	0.012	0.088	0.18	4	-0.31	25	29
B-cell antigen/BCR complex	-0.018	0.084	-10000	0	-0.21	75	75
PAG1/CSK	0.015	0.019	-10000	0	-0.29	2	2
NFKBIB	0.019	0.02	0.082	1	-0.12	1	2
HRAS	0.023	0.067	0.16	6	-0.23	16	22
NFKBIA	0.019	0.02	0.082	1	-0.12	1	2
NF-kappa-B/RelA/I kappa B beta	0.022	0.019	0.084	1	-0.14	1	2
RasGAP/Csk	0.004	0.065	-10000	0	-0.19	32	32
mol:GDP	0.017	0.075	0.17	62	-0.25	16	78
PTEN	0.006	0.046	-10000	0	-0.42	6	6
CD79B	-0.006	0.083	-10000	0	-0.42	20	20
NF-kappa-B/RelA/I kappa B alpha	0.022	0.019	0.084	1	-0.14	1	2
GRB2	0.011	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	0.016	0.11	-10000	0	-0.45	21	21
PIK3R1	0.007	0.038	-10000	0	-0.42	4	4
mol:IP3	0.018	0.08	0.18	62	-0.27	16	78
CSK	0.011	0	-10000	0	-10000	0	0
FOS	-0.036	0.12	0.17	39	-0.29	20	59
CHUK	0.03	0.046	0.16	1	-0.18	1	2
IBTK	0.011	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.009	0.041	-10000	0	-0.3	2	2
PTPN6	-0.028	0.13	-10000	0	-0.46	27	27
RELA	0.011	0	-10000	0	-10000	0	0
BCL2A1	0.019	0.015	-10000	0	-10000	0	0
VAV2	-0.002	0.099	-10000	0	-0.43	20	20
ubiquitin-dependent protein catabolic process	0.022	0.02	0.085	1	-0.12	1	2
BTK	-0.009	0.093	-10000	0	-1	4	4
CD19	-0.033	0.093	-10000	0	-0.41	23	23
MAP4K1	0.004	0.043	-10000	0	-0.27	12	12
CD72	0.009	0.022	-10000	0	-0.27	3	3
PAG1	0.009	0.027	-10000	0	-0.42	2	2
MAPK14	0.011	0.092	-10000	0	-0.36	23	23
SH3BP5	-0.052	0.15	-10000	0	-0.42	75	75
PIK3AP1	0.026	0.087	0.2	60	-0.3	16	76
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	0.016	0.05	-10000	0	-0.31	5	5
RAF1	0.027	0.064	0.17	2	-0.21	16	18
RasGAP/p62DOK/SHIP	-0.021	0.05	-10000	0	-0.29	2	2
CD79A	-0.022	0.092	-10000	0	-0.28	56	56
re-entry into mitotic cell cycle	-0.003	0.074	0.14	35	-0.19	24	59
RASA1	0.006	0.042	-10000	0	-0.42	5	5
MAPK3	0.035	0.058	0.18	1	-0.25	2	3
MAPK1	0.035	0.058	0.18	1	-0.25	2	3
CD72/SHP1	-0.021	0.12	-10000	0	-0.45	25	25
NFKB1	0.01	0.019	-10000	0	-0.42	1	1
MAPK8	0.01	0.095	-10000	0	-0.35	25	25
actin cytoskeleton organization	0.005	0.089	-10000	0	-0.38	20	20
NF-kappa-B/RelA	0.047	0.036	0.16	1	-0.18	1	2
Calcineurin	-0.008	0.04	-10000	0	-0.21	17	17
PI3K	-0.036	0.087	-10000	0	-0.36	24	24
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	0.023	0.09	0.2	66	-0.31	16	82
SOS1	0.011	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.037	0.2	-10000	0	-0.69	41	41
DAPP1	-0.065	0.22	-10000	0	-0.78	41	41
cytokine secretion	0.013	0.084	0.18	4	-0.29	25	29
mol:DAG	0.018	0.08	0.18	62	-0.27	16	78
PLCG2	0.01	0.019	-10000	0	-0.42	1	1
MAP2K1	0.031	0.061	0.19	1	-0.28	2	3
B-cell antigen/BCR complex/FcgammaRIIB	-0.008	0.073	-10000	0	-0.24	27	27
mol:PI-3-4-5-P3	-0.029	0.068	0.21	5	-0.26	24	29
ETS1	0.031	0.07	0.17	62	-0.21	16	78
B-cell antigen/BCR complex/LYN/SYK/BLNK	0.007	0.061	-10000	0	-0.19	25	25
B-cell antigen/BCR complex/LYN	-0.028	0.094	-10000	0	-0.42	25	25
MALT1	0.011	0	-10000	0	-10000	0	0
TRAF6	0.01	0	-10000	0	-10000	0	0
RAC1	0.005	0.093	-10000	0	-0.4	20	20
B-cell antigen/BCR complex/LYN/SYK	-0.035	0.11	-10000	0	-0.45	24	24
CARD11	0.019	0.078	0.17	60	-0.25	16	76
FCGR2B	0.008	0.035	-10000	0	-0.38	4	4
PPP3CA	0.011	0	-10000	0	-10000	0	0
BCL10	0.011	0	-10000	0	-10000	0	0
IKK complex	0.02	0.023	0.11	1	-10000	0	1
PTPRC	0.001	0.063	-10000	0	-0.4	12	12
PDPK1	0.002	0.057	0.16	5	-0.18	22	27
PPP3CB	0.011	0	-10000	0	-10000	0	0
PPP3CC	0.008	0.033	-10000	0	-0.42	3	3
POU2F2	0.02	0.014	-10000	0	-0.095	1	1

×

Regulation of Androgen receptor activity

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.018	0	-9999	-10000	0	0
SMARCC1	0.006	0.016	-9999	-10000	0	0
REL	0.01	0.001	-9999	-10000	0	0
HDAC7	0.022	0.06	-9999	-0.27	3	3
JUN	0.006	0.046	-9999	-0.42	6	6
EP300	0.011	0	-9999	-10000	0	0
KAT2B	0.002	0.059	-9999	-0.42	10	10
KAT5	0.011	0	-9999	-10000	0	0
MAPK14	-0.005	0.063	-9999	-0.17	65	65
FOXO1	0.008	0.033	-9999	-0.42	3	3
T-DHT/AR	0.021	0.065	-9999	-0.25	8	8
MAP2K6	-0.024	0.093	-9999	-0.27	65	65
BRM/BAF57	0.007	0.051	-9999	-0.28	15	15
MAP2K4	0.011	0.019	-9999	-0.41	1	1
SMARCA2	-0.002	0.072	-9999	-0.42	15	15
PDE9A	-0.02	0.1	-9999	-0.99	4	4
NCOA2	-0.004	0.079	-9999	-0.42	18	18
CEBPA	0.007	0.035	-9999	-0.38	4	4
EHMT2	0.011	0	-9999	-10000	0	0
cell proliferation	0.015	0.11	-9999	-0.35	17	17
NR0B1	-0.005	0.05	-9999	-0.27	17	17
EGR1	-0.061	0.16	-9999	-0.42	86	86
RXRs/9cRA	-0.004	0.069	-9999	-0.21	48	48
AR/RACK1/Src	0.014	0.058	-9999	-0.27	3	3
AR/GR	-0.056	0.12	-9999	-0.22	166	166
GNB2L1	0.011	0.002	-9999	-10000	0	0
PKN1	0.011	0	-9999	-10000	0	0
RCHY1	0.011	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0.001	-9999	-10000	0	0
MAPK8	0.016	0.033	-9999	-0.28	6	6
T-DHT/AR/TIF2/CARM1	0.008	0.076	-9999	-0.31	13	13
SRC	0.015	0.05	-9999	-0.2	5	5
NR3C1	-0.068	0.16	-9999	-0.42	94	94
KLK3	-0.034	0.088	-9999	-0.46	1	1
APPBP2	0.011	0.002	-9999	-10000	0	0
TRIM24	0.011	0.001	-9999	-10000	0	0
T-DHT/AR/TIP60	0.007	0.055	-9999	-0.25	5	5
TMPRSS2	-0.03	0.14	-9999	-1	8	8
RXRG	-0.035	0.13	-9999	-0.39	57	57
mol:9cRA	0	0	-9999	-10000	0	0
RXRA	0.011	0	-9999	-10000	0	0
RXRB	0.011	0	-9999	-10000	0	0
CARM1	0.011	0.002	-9999	-10000	0	0
NR2C2	0.002	0.059	-9999	-0.42	10	10
KLK2	0.005	0.12	-9999	-0.54	19	19
AR	-0.022	0.099	-9999	-0.22	90	90
SENP1	0.011	0	-9999	-10000	0	0
HSP90AA1	0.011	0	-9999	-10000	0	0
MDM2	0.01	0.001	-9999	-10000	0	0
SRY	0	0.001	-9999	-10000	0	0
GATA2	-0.029	0.12	-9999	-0.42	48	48
MYST2	0.011	0	-9999	-10000	0	0
HOXB13	-0.18	0.13	-9999	-0.27	345	345
T-DHT/AR/RACK1/Src	0.013	0.056	-9999	-0.32	2	2
positive regulation of transcription	-0.029	0.12	-9999	-0.42	48	48
DNAJA1	0.011	0.002	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.022	0	-9999	-10000	0	0
NCOA1	0.013	0.02	-9999	-0.45	1	1
SPDEF	-0.1	0.15	-9999	-0.29	200	200
T-DHT/AR/TIF2	0.011	0.071	-9999	-0.29	15	15
T-DHT/AR/Hsp90	0.008	0.056	-9999	-0.25	5	5
GSK3B	0.011	0.001	-9999	-10000	0	0
NR2C1	0.01	0	-9999	-10000	0	0
mol:T-DHT	0.01	0.054	-9999	-0.22	6	6
SIRT1	0.009	0.027	-9999	-0.42	2	2
ZMIZ2	0.01	0.001	-9999	-10000	0	0
POU2F1	0.02	0.012	-9999	-10000	0	0
T-DHT/AR/DAX-1	0.003	0.061	-9999	-0.26	6	6
CREBBP	0.01	0.019	-9999	-0.42	1	1
SMARCE1	0.011	0.001	-9999	-10000	0	0

×

EPHB forward 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
Ephrin A5/EPHB2	0.006	0.043	-10000	0	-0.22	18	18
cell-cell adhesion	0.029	0.064	0.31	8	-10000	0	8
Ephrin B/EPHB2/RasGAP	0.008	0.068	-10000	0	-0.19	53	53
ITSN1	0.011	0	-10000	0	-10000	0	0
PIK3CA	0.01	0.019	-10000	0	-0.42	1	1
SHC1	0.011	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	0.007	0.036	-10000	0	-0.17	20	20
Ephrin B1/EPHB1	-0.009	0.073	-10000	0	-0.24	47	47
HRAS/GDP	-0.029	0.067	-10000	0	-0.31	9	9
Ephrin B/EPHB1/GRB7	-0.017	0.095	-10000	0	-0.21	89	89
Endophilin/SYNJ1	0.009	0.061	-10000	0	-0.18	48	48
KRAS	0.01	0.012	-10000	0	-0.27	1	1
Ephrin B/EPHB1/Src	-0.009	0.091	-10000	0	-0.2	88	88
endothelial cell migration	-0.003	0.025	-10000	0	-0.19	9	9
GRB2	0.011	0	-10000	0	-10000	0	0
GRB7	-0.007	0.07	-10000	0	-0.28	31	31
PAK1	0.012	0.066	-10000	0	-0.36	3	3
HRAS	0.011	0	-10000	0	-10000	0	0
RRAS	0.008	0.062	-10000	0	-0.18	49	49
DNM1	0.008	0.033	-10000	0	-0.42	3	3
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.009	0.086	-10000	0	-0.19	88	88
lamellipodium assembly	-0.029	0.064	-10000	0	-0.31	8	8
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.008	0.088	-10000	0	-0.22	49	49
PIK3R1	0.007	0.038	-10000	0	-0.42	4	4
EPHB2	0.01	0.018	-10000	0	-0.27	2	2
EPHB3	-0.002	0.063	-10000	0	-0.31	20	20
EPHB1	-0.028	0.12	-10000	0	-0.41	47	47
EPHB4	0.01	0.019	-10000	0	-0.42	1	1
mol:GDP	-0.001	0.083	-10000	0	-0.23	40	40
Ephrin B/EPHB2	0.004	0.065	-10000	0	-0.2	48	48
Ephrin B/EPHB3	-0.001	0.078	-10000	0	-0.22	51	51
JNK cascade	0.009	0.063	-10000	0	-0.19	47	47
Ephrin B/EPHB1	-0.015	0.09	-10000	0	-0.21	88	88
RAP1/GDP	0.01	0.076	-10000	0	-0.28	9	9
EFNB2	0.008	0.033	-10000	0	-0.42	3	3
EFNB3	-0.028	0.12	-10000	0	-0.42	46	46
EFNB1	0.011	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.002	0.068	-10000	0	-0.21	49	49
RAP1B	0.011	0	-10000	0	-10000	0	0
RAP1A	0.011	0	-10000	0	-10000	0	0
CDC42/GTP	-0.033	0.073	-10000	0	-0.36	8	8
Rap1/GTP	-0.028	0.062	-10000	0	-0.31	8	8
axon guidance	0.006	0.043	-10000	0	-0.22	18	18
MAPK3	0.004	0.079	-10000	0	-0.33	7	7
MAPK1	0.004	0.079	-10000	0	-0.33	7	7
Rac1/GDP	0.006	0.078	-10000	0	-0.21	40	40
actin cytoskeleton reorganization	-0.023	0.051	-10000	0	-0.25	8	8
CDC42/GDP	0.006	0.078	-10000	0	-0.21	40	40
PI3K	0.021	0.028	-10000	0	-0.19	9	9
EFNA5	-0.002	0.072	-10000	0	-0.4	16	16
Ephrin B2/EPHB4	0.012	0.022	-10000	0	-0.24	4	4
Ephrin B/EPHB2/Intersectin/N-WASP	0.008	0.067	-10000	0	-0.2	48	48
CDC42	0.011	0	-10000	0	-10000	0	0
RAS family/GTP	-0.027	0.061	-10000	0	-0.31	8	8
PTK2	0.006	0.018	-10000	0	-10000	0	0
MAP4K4	0.009	0.064	-10000	0	-0.19	47	47
SRC	0.011	0	-10000	0	-10000	0	0
KALRN	0.006	0.042	-10000	0	-0.42	5	5
Intersectin/N-WASP	0.016	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.018	0.08	-10000	0	-0.28	10	10
MAP2K1	-0.001	0.083	-10000	0	-0.35	7	7
WASL	0.011	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	0.005	0.069	-10000	0	-0.21	47	47
cell migration	-0.003	0.097	-10000	0	-0.38	8	8
NRAS	0.011	0	-10000	0	-10000	0	0
SYNJ1	0.009	0.061	-10000	0	-0.18	48	48
PXN	0.011	0	-10000	0	-10000	0	0
TF	0.005	0.069	-10000	0	-0.27	6	6
HRAS/GTP	-0.031	0.068	-10000	0	-0.34	8	8
Ephrin B1/EPHB1-2	-0.001	0.066	-10000	0	-0.21	46	46
cell adhesion mediated by integrin	0.016	0.065	0.21	48	-10000	0	48
RAC1	0.011	0	-10000	0	-10000	0	0
mol:GTP	-0.006	0.086	-10000	0	-0.36	8	8
RAC1-CDC42/GTP	-0.032	0.07	-10000	0	-0.3	17	17
RASA1	0.006	0.042	-10000	0	-0.42	5	5
RAC1-CDC42/GDP	0.01	0.076	-10000	0	-0.28	9	9
ruffle organization	0.009	0.08	-10000	0	-0.31	8	8
NCK1	0.009	0.027	-10000	0	-0.42	2	2
receptor internalization	0.013	0.062	-10000	0	-0.26	4	4
Ephrin B/EPHB2/KALRN	0.008	0.07	-10000	0	-0.2	51	51
ROCK1	0.013	0.032	-10000	0	-0.21	5	5
RAS family/GDP	-0.022	0.051	-10000	0	-0.25	8	8
Rac1/GTP	-0.03	0.066	-10000	0	-0.33	8	8
Ephrin B/EPHB1/Src/Paxillin	-0.012	0.093	-10000	0	-0.21	88	88

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.098	0.19	-9999	-0.42	131	131
CDC42/GTP	-0.035	0.11	-9999	-0.36	17	17
PLCG1	-0.036	0.11	-9999	-0.38	16	16
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.011	0	-9999	-10000	0	0
GNAI3	0.011	0	-9999	-10000	0	0
G12/G13	0.016	0	-9999	-10000	0	0
cell migration	-0.034	0.1	-9999	-0.35	17	17
S1PR5	0.002	0.05	-9999	-0.28	15	15
S1PR4	0.009	0.023	-9999	-0.34	2	2
MAPK3	-0.036	0.11	-9999	-0.38	16	16
MAPK1	-0.036	0.11	-9999	-0.38	16	16
S1P/S1P5/Gi	-0.046	0.12	-9999	-0.22	133	133
GNAI1	0.002	0.059	-9999	-0.42	10	10
CDC42/GDP	0.008	0	-9999	-10000	0	0
S1P/S1P5/G12	0.01	0.028	-9999	-0.15	15	15
RHOA	0.023	0.011	-9999	-0.19	1	1
S1P/S1P4/Gi	-0.044	0.12	-9999	-0.22	132	132
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.011	0.094	-9999	-0.42	26	26
S1P/S1P4/G12/G13	0.02	0.012	-9999	-0.21	1	1
GNA12	0.011	0	-9999	-10000	0	0
GNA13	0.011	0	-9999	-10000	0	0
CDC42	0.011	0	-9999	-10000	0	0

×

Syndecan-2-mediated 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.011	0.046	-9999	-0.23	18	18
EPHB2	0.01	0.018	-9999	-0.27	2	2
Syndecan-2/TACI	0.006	0.048	-9999	-0.19	27	27
LAMA1	-0.11	0.14	-9999	-0.27	223	223
Syndecan-2/alpha2 ITGB1	0.015	0.062	-9999	-0.21	34	34
HRAS	0.011	0	-9999	-10000	0	0
Syndecan-2/CASK	0.005	0.039	-9999	-0.24	13	13
ITGA5	0.01	0.019	-9999	-0.42	1	1
BAX	0.022	0.041	-9999	-10000	0	0
EPB41	0.011	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	0.012	0.035	-9999	-0.21	13	13
LAMA3	0	0.067	-9999	-0.42	13	13
EZR	0.011	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.029	0.12	-9999	-0.42	48	48
Syndecan-2/MMP2	0	0.07	-9999	-0.24	37	37
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	0.009	0.046	-9999	-0.29	12	12
dendrite morphogenesis	0.012	0.04	-9999	-0.22	15	15
Syndecan-2/GM-CSF	0.008	0.042	-9999	-0.21	17	17
determination of left/right symmetry	0.008	0.047	-9999	-0.28	13	13
Syndecan-2/PKC delta	0.013	0.039	-9999	-0.23	13	13
GNB2L1	0.011	0	-9999	-10000	0	0
MAPK3	0.015	0.037	-9999	-0.2	13	13
MAPK1	0.015	0.037	-9999	-0.2	13	13
Syndecan-2/RACK1	0.018	0.034	-9999	-0.19	13	13
NF1	0.008	0.033	-9999	-0.42	3	3
FGFR/FGF/Syndecan-2	0.008	0.047	-9999	-0.28	13	13
ITGA2	0.001	0.065	-9999	-0.42	12	12
MAPK8	0.017	0.047	-9999	-0.23	18	18
Syndecan-2/alpha2/beta1 Integrin	-0.038	0.08	-9999	-0.24	26	26
Syndecan-2/Kininogen	0.001	0.051	-9999	-0.17	38	38
ITGB1	0.011	0	-9999	-10000	0	0
SRC	0.023	0.032	-9999	-0.18	13	13
Syndecan-2/CASK/Protein 4.1	0.012	0.036	-9999	-0.21	13	13
extracellular matrix organization	0.012	0.041	-9999	-0.23	14	14
actin cytoskeleton reorganization	0.01	0.046	-9999	-0.23	18	18
Syndecan-2/Caveolin-2/Ras	-0.002	0.076	-9999	-0.21	59	59
Syndecan-2/Laminin alpha3	0.007	0.057	-9999	-0.24	25	25
Syndecan-2/RasGAP	0.021	0.038	-9999	-0.18	18	18
alpha5/beta1 Integrin	0.015	0.013	-9999	-0.29	1	1
PRKCD	0.011	0	-9999	-10000	0	0
Syndecan-2 dimer	0.012	0.041	-9999	-0.22	15	15
GO:0007205	0.003	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.027	0.037	-9999	-0.17	18	18
RHOA	0.011	0	-9999	-10000	0	0
SDCBP	0.011	0	-9999	-10000	0	0
TNFRSF13B	0	0.047	-9999	-0.27	15	15
RASA1	0.006	0.042	-9999	-0.42	5	5
alpha2/beta1 Integrin	0.009	0.046	-9999	-0.29	12	12
Syndecan-2/Synbindin	0.013	0.039	-9999	-0.23	13	13
TGFB1	0.01	0.019	-9999	-0.42	1	1
CASP3	0.019	0.036	-9999	-0.2	13	13
FN1	0.006	0.042	-9999	-0.42	5	5
Syndecan-2/IL8	-0.018	0.072	-9999	-0.15	113	113
SDC2	0.008	0.047	-9999	-0.29	13	13
KNG1	-0.008	0.06	-9999	-0.27	25	25
Syndecan-2/Neurofibromin	0.011	0.044	-9999	-0.23	16	16
TRAPPC4	0.011	0	-9999	-10000	0	0
CSF2	0.004	0.025	-9999	-0.27	4	4
Syndecan-2/TGFB1	0.012	0.041	-9999	-0.23	14	14
Syndecan-2/Syntenin/PI-4-5-P2	0.012	0.036	-9999	-0.21	13	13
Syndecan-2/Ezrin	0.019	0.036	-9999	-0.2	13	13
PRKACA	0.018	0.039	-9999	-0.2	16	16
angiogenesis	-0.018	0.072	-9999	-0.15	113	113
MMP2	-0.011	0.094	-9999	-0.42	26	26
IL8	-0.045	0.11	-9999	-0.27	101	101
calcineurin-NFAT signaling pathway	0.006	0.048	-9999	-0.19	27	27

×

Signaling events mediated by PTP1B

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
PDGFRB	-0.007	0.085	-10000	0	-0.42	21	21
Jak2/Leptin Receptor	-0.1	0.15	-10000	0	-0.36	86	86
PTP1B/AKT1	0.013	0.044	-10000	0	-0.22	7	7
FYN	0.011	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	0.009	0.048	-10000	0	-0.25	7	7
EGFR	0	0.069	-10000	0	-0.41	14	14
EGF/EGFR	-0.012	0.054	0.13	1	-0.25	19	20
CSF1	0.002	0.059	-10000	0	-0.42	10	10
AKT1	0.011	0.001	-10000	0	-10000	0	0
INSR	0.011	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.006	0.084	-10000	0	-0.26	33	33
Insulin Receptor/Insulin	-0.01	0.026	-10000	0	-0.23	1	1
HCK	0.01	0.012	-10000	0	-0.27	1	1
CRK	0.011	0	-10000	0	-10000	0	0
TYK2	0.014	0.046	-10000	0	-0.23	7	7
EGF	-0.001	0.058	-10000	0	-0.28	20	20
YES1	0.011	0	-10000	0	-10000	0	0
CAV1	-0.011	0.084	-10000	0	-0.3	15	15
TXN	0.011	0.002	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	0.002	0.08	-10000	0	-0.24	32	32
cell migration	-0.009	0.048	0.25	7	-10000	0	7
STAT3	0.011	0.001	-10000	0	-10000	0	0
PRLR	-0.074	0.17	-10000	0	-0.42	101	101
ITGA2B	0.004	0.047	-10000	0	-0.36	8	8
CSF1R	0.008	0.033	-10000	0	-0.42	3	3
Prolactin Receptor/Prolactin	-0.06	0.14	-10000	0	-0.3	118	118
FGR	0	0.067	-10000	0	-0.42	13	13
PTP1B/p130 Cas	0.014	0.046	-10000	0	-0.23	7	7
Crk/p130 Cas	0.02	0.045	-10000	0	-0.22	7	7
DOK1	0.011	0.061	-10000	0	-0.23	19	19
JAK2	-0.042	0.13	-10000	0	-0.26	108	108
Jak2/Leptin Receptor/Leptin	-0.019	0.06	-10000	0	-0.32	14	14
PIK3R1	0.007	0.038	-10000	0	-0.42	4	4
PTPN1	0.009	0.049	-10000	0	-0.25	7	7
LYN	0.011	0	-10000	0	-10000	0	0
CDH2	-0.032	0.13	-10000	0	-0.41	52	52
SRC	0.017	0.02	-10000	0	-10000	0	0
ITGB3	-0.078	0.17	-10000	0	-0.42	107	107
CAT1/PTP1B	0.017	0.07	-10000	0	-0.33	7	7
CAPN1	0.011	0.001	-10000	0	-10000	0	0
CSK	0.011	0	-10000	0	-10000	0	0
PI3K	-0.009	0.028	-10000	0	-0.23	3	3
mol:H2O2	0	0.001	-10000	0	-10000	0	0
STAT3 (dimer)	-0.017	0.057	-10000	0	-0.32	13	13
negative regulation of transcription	-0.042	0.13	-10000	0	-0.26	108	108
FCGR2A	0.01	0.012	-10000	0	-0.27	1	1
FER	0.011	0.002	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.051	0.13	-10000	0	-0.28	114	114
BLK	-0.014	0.077	-10000	0	-0.27	42	42
Insulin Receptor/Insulin/Shc	0.015	0.002	-10000	0	-10000	0	0
RHOA	0.011	0.001	-10000	0	-10000	0	0
LEPR	-0.12	0.19	-10000	0	-0.41	152	152
BCAR1	0.011	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.011	0	-10000	0	-10000	0	0
mol:NADPH	0.001	0.001	-10000	0	-10000	0	0
TRPV6	0.015	0.06	-10000	0	-0.41	3	3
PRL	-0.012	0.089	-10000	0	-0.41	24	24
SOCS3	-0.003	0.13	-10000	0	-1.2	6	6
SPRY2	0.006	0.046	-10000	0	-0.42	6	6
Insulin Receptor/Insulin/IRS1	-0.008	0.074	-10000	0	-0.24	47	47
CSF1/CSF1R	0.015	0.06	-10000	0	-0.26	15	15
Ras protein signal transduction	0.008	0.015	-10000	0	-10000	0	0
IRS1	-0.029	0.12	-10000	0	-0.42	47	47
INS	0.001	0.003	-10000	0	-10000	0	0
LEP	0.005	0.022	-10000	0	-0.27	3	3
STAT5B	-0.007	0.069	-10000	0	-0.24	21	21
STAT5A	-0.007	0.068	-10000	0	-0.24	20	20
GRB2	0.011	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.006	0.066	-10000	0	-0.23	28	28
CSN2	-0.03	0.062	-10000	0	-10000	0	0
PIK3CA	0.01	0.019	-10000	0	-0.42	1	1
LAT	0.017	0.02	-10000	0	-10000	0	0
YBX1	0.016	0.019	-10000	0	-0.41	1	1
LCK	0.008	0.031	-10000	0	-0.3	5	5
SHC1	0.011	0	-10000	0	-10000	0	0
NOX4	0.004	0.052	-10000	0	-0.4	8	8

×

Hedgehog signaling events mediated by Gli proteins

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.011	0	-9999	-10000	0	0
HDAC2	0.011	0.001	-9999	-10000	0	0
GNB1/GNG2	0.012	0.047	-9999	-0.23	18	18
forebrain development	-0.054	0.18	-9999	-0.45	79	79
GNAO1	-0.098	0.19	-9999	-0.42	131	131
SMO/beta Arrestin2	0.015	0.027	-9999	-0.28	4	4
SMO	0.008	0.038	-9999	-0.42	4	4
ARRB2	0.011	0.003	-9999	-10000	0	0
GLI3/SPOP	-0.038	0.12	-9999	-0.21	148	148
mol:GTP	0	0.001	-9999	-10000	0	0
GSK3B	0.011	0	-9999	-10000	0	0
GNAI2	0.011	0.002	-9999	-10000	0	0
SIN3/HDAC complex	0.027	0.002	-9999	-10000	0	0
GNAI1	0.002	0.059	-9999	-0.42	10	10
XPO1	0.012	0.004	-9999	-10000	0	0
GLI1/Su(fu)	-0.056	0.12	-9999	-0.45	27	27
SAP30	0.011	0.001	-9999	-10000	0	0
mol:GDP	0.008	0.038	-9999	-0.42	4	4
MIM/GLI2A	0.013	0.016	-9999	-10000	0	0
IFT88	0.011	0	-9999	-10000	0	0
GNAI3	0.011	0.002	-9999	-10000	0	0
GLI2	-0.009	0.076	-9999	-10000	0	0
GLI3	-0.046	0.12	-9999	-0.22	158	158
CSNK1D	0.011	0	-9999	-10000	0	0
CSNK1E	0.011	0	-9999	-10000	0	0
SAP18	0.011	0	-9999	-10000	0	0
embryonic digit morphogenesis	0.011	0	-9999	-10000	0	0
GNG2	-0.002	0.071	-9999	-0.41	15	15
Gi family/GTP	-0.044	0.12	-9999	-0.27	55	55
SIN3B	0.011	0.001	-9999	-10000	0	0
SIN3A	0.011	0	-9999	-10000	0	0
GLI3/Su(fu)	-0.012	0.09	-9999	-0.39	3	3
GLI2/Su(fu)	0.007	0.069	-9999	-0.24	3	3
FOXA2	-0.084	0.28	-9999	-1.1	39	39
neural tube patterning	-0.054	0.18	-9999	-0.45	79	79
SPOP	0.011	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.025	0.015	-9999	-10000	0	0
GNB1	0.011	0	-9999	-10000	0	0
CSNK1G2	0.011	0	-9999	-10000	0	0
CSNK1G3	0.011	0	-9999	-10000	0	0
MTSS1	0.013	0.016	-9999	-10000	0	0
embryonic limb morphogenesis	-0.054	0.18	-9999	-0.45	79	79
SUFU	0.021	0.017	-9999	-10000	0	0
LGALS3	0.009	0.027	-9999	-0.42	2	2
catabolic process	-0.041	0.13	-9999	-0.28	72	72
GLI3A/CBP	-0.032	0.12	-9999	-0.31	77	77
KIF3A	0.01	0.019	-9999	-0.42	1	1
GLI1	-0.055	0.19	-9999	-0.46	79	79
RAB23	0.005	0.05	-9999	-0.42	7	7
CSNK1A1	0.011	0	-9999	-10000	0	0
IFT172	0.011	0	-9999	-10000	0	0
RBBP7	0.011	0.001	-9999	-10000	0	0
Su(fu)/Galectin3	0.024	0.021	-9999	-0.2	2	2
GNAZ	-0.011	0.094	-9999	-0.42	26	26
RBBP4	0.009	0.027	-9999	-0.42	2	2
CSNK1G1	0.011	0	-9999	-10000	0	0
PIAS1	0.011	0	-9999	-10000	0	0
PRKACA	0.011	0	-9999	-10000	0	0
GLI2/SPOP	-0.003	0.071	-9999	-10000	0	0
STK36	0.012	0.004	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.037	0.11	-9999	-0.37	24	24
PTCH1	-0.042	0.17	-9999	-0.54	26	26
MIM/GLI1	-0.058	0.22	-9999	-0.48	96	96
CREBBP	-0.032	0.12	-9999	-0.31	77	77
Su(fu)/SIN3/HDAC complex	0.037	0.014	-9999	-10000	0	0

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.007	0.085	-9999	-0.42	21	21
alphaV beta3 Integrin	-0.047	0.12	-9999	-0.28	107	107
PTK2	-0.041	0.09	-9999	-0.38	24	24
positive regulation of JNK cascade	-0.016	0.06	-9999	-0.28	24	24
CDC42/GDP	0.014	0.091	-9999	-0.38	24	24
Rac1/GDP	0.015	0.09	-9999	-0.37	24	24
RAP1B	0.011	0	-9999	-10000	0	0
RAP1A	0.011	0	-9999	-10000	0	0
CTNNB1	0.011	0	-9999	-10000	0	0
CDC42/GTP	-0.02	0.073	-9999	-0.34	24	24
nectin-3/I-afadin	0.002	0.064	-9999	-0.29	24	24
RAPGEF1	0.008	0.098	-9999	-0.41	24	24
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.001	0.11	-9999	-0.47	24	24
PDGFB-D/PDGFRB	-0.007	0.085	-9999	-0.42	21	21
TLN1	0	0.077	-9999	-0.27	32	32
Rap1/GTP	-0.016	0.063	-9999	-0.3	24	24
IQGAP1	0.011	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.021	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.002	0.064	-9999	-0.29	24	24
PVR	0.011	0	-9999	-10000	0	0
Necl-5(dimer)	0.011	0	-9999	-10000	0	0
mol:GDP	0.009	0.11	-9999	-0.46	24	24
MLLT4	0.011	0	-9999	-10000	0	0
PIK3CA	0.01	0.019	-9999	-0.42	1	1
PI3K	0.011	0.071	-9999	-0.21	44	44
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.015	0.008	-9999	-0.18	1	1
positive regulation of lamellipodium assembly	-0.017	0.063	-9999	-0.3	24	24
PVRL1	0.01	0.012	-9999	-0.27	1	1
PVRL3	-0.009	0.09	-9999	-0.42	24	24
PVRL2	0.011	0	-9999	-10000	0	0
PIK3R1	0.007	0.038	-9999	-0.42	4	4
CDH1	0.008	0.029	-9999	-0.37	3	3
CLDN1	-0.078	0.17	-9999	-0.42	106	106
JAM-A/CLDN1	-0.031	0.11	-9999	-0.22	123	123
SRC	-0.006	0.12	-9999	-0.52	24	24
ITGB3	-0.078	0.17	-9999	-0.41	107	107
nectin-1(dimer)/I-afadin/I-afadin	0.015	0.008	-9999	-0.18	1	1
FARP2	0.005	0.11	-9999	-0.45	24	24
RAC1	0.011	0	-9999	-10000	0	0
CTNNA1	0.011	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.01	0.054	-9999	-0.23	24	24
nectin-1/I-afadin	0.015	0.008	-9999	-0.18	1	1
nectin-2/I-afadin	0.016	0	-9999	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0.014	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.009	0.055	-9999	-0.24	24	24
CDC42/GTP/IQGAP1/filamentous actin	0.014	0	-9999	-10000	0	0
F11R	0.01	0.019	-9999	-0.42	1	1
positive regulation of filopodium formation	-0.016	0.06	-9999	-0.28	24	24
alphaV/beta3 Integrin/Talin	-0.029	0.12	-9999	-0.34	38	38
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.016	0	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.016	0	-9999	-10000	0	0
PIP5K1C	-0.006	0.082	-9999	-0.23	55	55
VAV2	0.004	0.11	-9999	-0.46	24	24
RAP1/GDP	-0.019	0.074	-9999	-0.35	24	24
ITGAV	0.011	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.01	0.054	-9999	-0.23	24	24
nectin-3(dimer)/I-afadin/I-afadin	0.002	0.064	-9999	-0.29	24	24
Rac1/GTP	-0.021	0.076	-9999	-0.36	24	24
PTPRM	-0.014	0.09	-9999	-0.26	55	55
E-cadherin/beta catenin/alpha catenin	-0.001	0.012	-9999	-0.17	2	2
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.011	0	-9999	-10000	0	0

×

Rapid glucocorticoid 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
Gs family/GDP/Gbeta gamma	-0.024	0.091	-10000	0	-0.21	96	96
MAPK9	0.007	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.003	0.027	-10000	0	-0.18	11	11
GNB1/GNG2	0.007	0.042	-10000	0	-0.23	15	15
GNB1	0.011	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.007	0	-10000	0	-10000	0	0
Gs family/GTP	-0.032	0.086	-10000	0	-0.22	88	88
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	0.011	0.023	0.062	88	-10000	0	88
GNAL	-0.063	0.16	-10000	0	-0.42	88	88
GNG2	-0.002	0.071	-10000	0	-0.41	15	15
CRH	-0.004	0.04	-10000	0	-0.27	11	11
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.004	0.029	-10000	0	-0.29	5	5
MAPK11	0.006	0.018	-10000	0	-0.29	2	2

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.16	0.21	-9999	-0.42	205	205
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.011	0	-9999	-10000	0	0
TCEB1	0.011	0	-9999	-10000	0	0
HIF1A/p53	0.024	0.01	-9999	-0.17	1	1
HIF1A	0.019	0.005	-9999	-10000	0	0
COPS5	0.011	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.031	0.01	-9999	-0.18	1	1
FIH (dimer)	0.011	0	-9999	-10000	0	0
CDKN2A	-0.11	0.14	-9999	-0.27	224	224
ARNT/IPAS	-0.1	0.15	-9999	-0.28	205	205
HIF1AN	0.011	0	-9999	-10000	0	0
GNB2L1	0.011	0	-9999	-10000	0	0
HIF1A/ARNT	0.025	0.004	-9999	-10000	0	0
CUL2	0.011	0	-9999	-10000	0	0
OS9	0.011	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	0.022	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.025	0.004	-9999	-10000	0	0
PHD1-3/OS9	0.026	0.015	-9999	-0.2	1	1
HIF1A/RACK1/Elongin B/Elongin C	0.033	0.004	-9999	-10000	0	0
VHL	0.01	0.019	-9999	-0.42	1	1
HSP90AA1	0.011	0	-9999	-10000	0	0
HIF1A/JAB1	0.025	0.004	-9999	-10000	0	0
EGLN3	0.008	0.029	-9999	-0.31	4	4
EGLN2	0.011	0	-9999	-10000	0	0
EGLN1	0.011	0	-9999	-10000	0	0
TP53	0.01	0.019	-9999	-0.42	1	1
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.029	0.023	-9999	-0.5	1	1
ARNT	0.011	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.011	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.028	0.06	-9999	-0.16	1	1

×

Presenilin action in Notch and Wnt signaling

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
Delta 1/NOTCH/NOTCH(cleaved)	-0.01	0.064	-10000	0	-0.66	4	4
HDAC1	0.008	0.005	-10000	0	-10000	0	0
AES	0.01	0.001	-10000	0	-10000	0	0
FBXW11	0.011	0	-10000	0	-10000	0	0
DTX1	0.006	0.042	-10000	0	-0.42	5	5
LRP6/FZD1	0.015	0.013	-10000	0	-0.29	1	1
TLE1	0.009	0.019	-10000	0	-0.42	1	1
AP1	-0.072	0.13	-10000	0	-0.24	175	175
NCSTN	0.011	0	-10000	0	-10000	0	0
ADAM10	0.007	0.038	-10000	0	-0.42	4	4
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.029	0.047	-10000	0	-0.6	1	1
NICD/RBPSUH	0.022	0.047	-10000	0	-0.51	4	4
WIF1	-0.081	0.14	-10000	0	-0.29	155	155
NOTCH1	-0.004	0.047	-10000	0	-0.54	4	4
PSENEN	0.011	0	-10000	0	-10000	0	0
KREMEN2	-0.017	0.084	-10000	0	-0.27	50	50
DKK1	-0.051	0.12	-10000	0	-0.28	108	108
beta catenin/beta TrCP1	0.025	0.024	-10000	0	-10000	0	0
APH1B	0.007	0.038	-10000	0	-0.42	4	4
APH1A	0.011	0	-10000	0	-10000	0	0
AXIN1	0.002	0.018	-10000	0	-0.18	4	4
CtBP/CBP/TCF1/TLE1/AES	0.015	0.028	-10000	0	-0.24	2	2
PSEN1	0.011	0	-10000	0	-10000	0	0
FOS	-0.13	0.2	-10000	0	-0.42	174	174
JUN	0.006	0.046	-10000	0	-0.42	6	6
MAP3K7	0.009	0.002	-10000	0	-10000	0	0
CTNNB1	0.019	0.026	0.16	5	-10000	0	5
MAPK3	0.011	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.013	0.082	-10000	0	-0.25	38	38
HNF1A	-0.006	0.065	-10000	0	-0.27	29	29
CTBP1	0.01	0.001	-10000	0	-10000	0	0
MYC	-0.005	0.18	-10000	0	-1.3	10	10
NKD1	-0.016	0.088	-10000	0	-0.3	44	44
FZD1	0.01	0.019	-10000	0	-0.42	1	1
NOTCH1 precursor/Deltex homolog 1	0.02	0.051	-10000	0	-0.51	4	4
apoptosis	-0.072	0.13	-10000	0	-0.24	175	175
Delta 1/NOTCHprecursor	0.016	0.067	-10000	0	-0.65	4	4
DLL1	-0.002	0.072	-10000	0	-0.42	15	15
PPARD	0.018	0.013	-10000	0	-10000	0	0
Gamma Secretase	0.03	0.019	-10000	0	-0.19	4	4
APC	0.002	0.018	-10000	0	-0.18	4	4
DVL1	0.002	0.013	-10000	0	-10000	0	0
CSNK2A1	0.011	0.001	-10000	0	-10000	0	0
MAP3K7IP1	-0.001	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.028	0.078	-10000	0	-0.26	10	10
LRP6	0.011	0	-10000	0	-10000	0	0
CSNK1A1	0.011	0.001	-10000	0	-10000	0	0
NLK	0.011	0.006	-10000	0	-10000	0	0
CCND1	0.018	0.013	-10000	0	-10000	0	0
WNT1	0.004	0.035	-10000	0	-0.27	8	8
Axin1/APC/beta catenin	0.029	0.024	-10000	0	-10000	0	0
DKK2	-0.021	0.11	-10000	0	-0.4	39	39
NOTCH1 precursor/DVL1	0.001	0.042	-10000	0	-0.46	4	4
GSK3B	0.01	0	-10000	0	-10000	0	0
FRAT1	0.01	0.001	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.006	0.049	-10000	0	-0.52	4	4
PPP2R5D	0.011	0.041	0.23	8	-10000	0	8
MAPK1	0.011	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.023	0.074	-10000	0	-0.21	22	22
RBPJ	0.011	0	-10000	0	-10000	0	0
CREBBP	0.012	0.019	-10000	0	-0.42	1	1

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.014	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.011	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.025	0.094	-9999	-0.27	65	65
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.01	0.019	-9999	-0.42	1	1
RAC1-CDC42/GTP/PAK family	-0.01	0.07	-9999	-0.18	76	76
response to UV	0	0	-9999	-10000	0	0
YES1	0.011	0	-9999	-10000	0	0
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.011	0	-9999	-10000	0	0
FYN	0.011	0	-9999	-10000	0	0
MAP3K12	0.007	0.038	-9999	-0.42	4	4
FGR	0	0.067	-9999	-0.42	13	13
p38 alpha/TAB1	-0.003	0.016	-9999	-0.18	2	2
PRKG1	-0.19	0.21	-9999	-0.42	242	242
DUSP8	0.006	0.042	-9999	-0.42	5	5
PGK/cGMP/p38 alpha	-0.073	0.078	-9999	-0.19	55	55
apoptosis	-0.003	0.016	-9999	-0.18	2	2
RAL/GTP	0.014	0	-9999	-10000	0	0
LYN	0.011	0	-9999	-10000	0	0
DUSP1	-0.11	0.19	-9999	-0.42	145	145
PAK1	0.011	0	-9999	-10000	0	0
SRC	0.011	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.027	0	-9999	-10000	0	0
TRAF6	0.011	0	-9999	-10000	0	0
RAC1	0.011	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0.011	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0.014	0	-9999	-10000	0	0
MAPK11	0.032	0.035	-9999	-0.2	1	1
BLK	-0.014	0.077	-9999	-0.27	42	42
HCK	0.01	0.012	-9999	-0.27	1	1
MAP2K3	0.011	0	-9999	-10000	0	0
DUSP16	0.011	0	-9999	-10000	0	0
DUSP10	0.011	0	-9999	-10000	0	0
TRAF6/MEKK3	0.014	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.035	0.027	-9999	-0.2	2	2
positive regulation of innate immune response	0.04	0.038	-9999	-0.22	1	1
LCK	0.008	0.031	-9999	-0.3	5	5
p38alpha-beta/MKP7	0.044	0.037	-9999	-0.21	1	1
p38alpha-beta/MKP5	0.044	0.037	-9999	-0.21	1	1
PGK/cGMP	-0.13	0.15	-9999	-0.29	242	242
PAK2	0.011	0	-9999	-10000	0	0
p38alpha-beta/MKP1	0.012	0.079	-9999	-0.26	14	14
CDC42	0.011	0	-9999	-10000	0	0
RALB	0.011	0	-9999	-10000	0	0
RALA	0.011	0	-9999	-10000	0	0
PAK3	-0.056	0.15	-9999	-0.42	76	76

×

Class I PI3K signaling events mediated by Akt

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.017	0.008	-9999	-0.18	1	1
BAD/BCL-XL/YWHAZ	0.026	0.006	-9999	-10000	0	0
CDKN1B	0.02	0.04	-9999	-0.23	1	1
CDKN1A	0.027	0.016	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
PRKDC	0.011	0	-9999	-10000	0	0
FOXO3	0.028	0.004	-9999	-10000	0	0
AKT1	0	0.002	-9999	-10000	0	0
BAD	0.011	0	-9999	-10000	0	0
AKT3	-0.11	0.14	-9999	-0.28	212	212
mol:GTP	0	0	-9999	-10000	0	0
FOXO4	0.027	0.013	-9999	-10000	0	0
AKT1/ASK1	0.026	0.015	-9999	-10000	0	0
BAD/YWHAZ	0.022	0	-9999	-10000	0	0
RICTOR	0.009	0.027	-9999	-0.42	2	2
RAF1	0.011	0	-9999	-10000	0	0
JNK cascade	-0.025	0.015	-9999	-10000	0	0
TSC1	0.028	0.01	-9999	-10000	0	0
YWHAZ	0.011	0	-9999	-10000	0	0
AKT1/RAF1	0.029	0.004	-9999	-10000	0	0
EP300	0.011	0	-9999	-10000	0	0
mol:GDP	0.024	0.004	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
TSC2	0.028	0.004	-9999	-10000	0	0
YWHAQ	0.011	0	-9999	-10000	0	0
TBC1D4	0.016	0.022	-9999	-0.23	4	4
MAP3K5	0.008	0.033	-9999	-0.42	3	3
MAPKAP1	0.011	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.017	0.009	-9999	-10000	0	0
YWHAH	0.011	0	-9999	-10000	0	0
AKT1S1	0.028	0.004	-9999	-10000	0	0
CASP9	0.028	0.004	-9999	-10000	0	0
YWHAB	0.011	0	-9999	-10000	0	0
p27Kip1/KPNA1	0.026	0.038	-9999	-0.22	1	1
GBL	0	0	-9999	-10000	0	0
PDK1/Src/Hsp90	0.022	0	-9999	-10000	0	0
YWHAE	0.011	0	-9999	-10000	0	0
SRC	0.011	0	-9999	-10000	0	0
AKT2/p21CIP1	0.03	0.015	-9999	-10000	0	0
KIAA1303	0	0	-9999	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.014	0.002	-9999	-10000	0	0
CHUK	0.028	0.004	-9999	-10000	0	0
BAD/BCL-XL	0.038	0.006	-9999	-10000	0	0
mTORC2	0.013	0.014	-9999	-0.22	2	2
AKT2	0.013	0	-9999	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.029	0.013	-9999	-10000	0	0
PDPK1	0.011	0	-9999	-10000	0	0
MDM2	0.028	0.004	-9999	-10000	0	0
MAPKKK cascade	-0.028	0.004	-9999	-10000	0	0
MDM2/Cbp/p300	0.038	0.009	-9999	-10000	0	0
TSC1/TSC2	0.032	0.009	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.036	0.009	-9999	-10000	0	0
glucose import	-0.095	0.11	-9999	-0.2	267	267
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.024	0.004	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	-0.096	0.11	-9999	-0.2	267	267
GSK3A	0.028	0.004	-9999	-10000	0	0
FOXO1	0.027	0.016	-9999	-10000	0	0
GSK3B	0.028	0.004	-9999	-10000	0	0
SFN	-0.21	0.12	-9999	-0.27	400	400
G1/S transition of mitotic cell cycle	0.033	0.004	-9999	-10000	0	0
p27Kip1/14-3-3 family	0.014	0.014	-9999	-10000	0	0
PRKACA	0.011	0	-9999	-10000	0	0
KPNA1	0.011	0	-9999	-10000	0	0
HSP90AA1	0.011	0	-9999	-10000	0	0
YWHAG	0.011	0	-9999	-10000	0	0
RHEB	0.011	0	-9999	-10000	0	0
CREBBP	0.01	0.019	-9999	-0.42	1	1

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.011	0	-9999	-10000	0	0
GNAT1/GTP	0.003	0.019	-9999	-0.18	5	5
Metarhodopsin II/Arrestin	0.006	0.014	-9999	-0.14	4	4
PDE6G/GNAT1/GTP	-0.003	0.046	-9999	-0.15	44	44
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.003	0.028	-9999	-0.27	5	5
GRK1	0.002	0.013	-9999	-0.27	1	1
CNG Channel	-0.02	0.048	-9999	-0.24	7	7
mol:Na +	-0.013	0.037	-9999	-0.2	6	6
mol:ADP	0.002	0.013	-9999	-0.27	1	1
RGS9-1/Gbeta5/R9AP	-0.043	0.11	-9999	-0.24	115	115
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.013	0.038	-9999	-0.21	6	6
CNGB1	-0.001	0.053	-9999	-0.27	19	19
RDH5	0.009	0.027	-9999	-0.42	2	2
SAG	0.004	0.013	-9999	-0.27	1	1
mol:Ca2+	0.016	0.044	-9999	-10000	0	0
Na + (4 Units)	-0.011	0.034	-9999	-0.2	1	1
RGS9	-0.085	0.18	-9999	-0.42	115	115
GNB1/GNGT1	-0.005	0.059	-9999	-0.18	56	56
GNAT1/GDP	-0.034	0.093	-9999	-0.2	116	116
GUCY2D	0.003	0.037	-9999	-0.27	9	9
GNGT1	-0.021	0.088	-9999	-0.27	56	56
GUCY2F	0.004	0.005	-9999	-10000	0	0
GNB5	0.011	0	-9999	-10000	0	0
mol:GMP (4 units)	0.003	0.054	-9999	-0.2	18	18
mol:11-cis-retinal	0.009	0.027	-9999	-0.42	2	2
mol:cGMP	0.01	0.037	-9999	-0.21	7	7
GNB1	0.011	0	-9999	-10000	0	0
Rhodopsin	0.009	0.024	-9999	-0.22	5	5
SLC24A1	0.011	0	-9999	-10000	0	0
CNGA1	0.002	0.048	-9999	-0.27	15	15
Metarhodopsin II	0.004	0.013	-9999	-0.13	4	4
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	0.008	0.039	-9999	-0.22	7	7
RGS9BP	-0.004	0.06	-9999	-0.27	24	24
Metarhodopsin II/Transducin	0.008	0.018	-9999	-10000	0	0
GCAP Family/Ca ++	0.005	0.033	-9999	-0.22	5	5
PDE6A/B	0.005	0.055	-9999	-0.26	20	20
mol:Pi	-0.043	0.11	-9999	-0.24	115	115
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	0	0.047	-9999	-0.26	2	2
PDE6B	-0.004	0.075	-9999	-0.39	18	18
PDE6A	0.009	0.023	-9999	-0.34	2	2
PDE6G	-0.012	0.077	-9999	-0.28	40	40
RHO	0.003	0.022	-9999	-0.27	3	3
PDE6	-0.057	0.084	-9999	-0.29	16	16
GUCA1A	-0.002	0.049	-9999	-0.27	16	16
GC2/GCAP Family	0.008	0.033	-9999	-0.21	5	5
GUCA1C	0	0	-9999	-10000	0	0
GUCA1B	0.006	0.042	-9999	-0.42	5	5

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.012	0.004	-10000	0	-10000	0	0
HSPA8	0.01	0.001	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.03	0.088	-10000	0	-0.26	60	60
AKT1	0.013	0.001	-10000	0	-10000	0	0
GSC	-0.021	0.056	-10000	0	-10000	0	0
NKX2-5	-0.034	0.096	-10000	0	-0.28	64	64
muscle cell differentiation	0.03	0.1	0.37	19	-10000	0	19
SMAD2-3/SMAD4/SP1	0.034	0.055	-10000	0	-0.3	4	4
SMAD4	0.006	0.036	-10000	0	-0.43	1	1
CBFB	0.011	0	-10000	0	-10000	0	0
SAP18	0.011	0	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.017	0.038	-10000	0	-0.27	4	4
SMAD3/SMAD4/VDR	0.008	0.038	-10000	0	-0.23	4	4
MYC	0	0.059	-10000	0	-0.42	10	10
CDKN2B	0.026	0.024	-10000	0	-10000	0	0
AP1	-0.033	0.13	-10000	0	-0.45	14	14
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.043	0.019	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.018	0.041	-10000	0	-0.39	2	2
SP3	0.013	0	-10000	0	-10000	0	0
CREB1	0.011	0	-10000	0	-10000	0	0
FOXH1	-0.063	0.12	-10000	0	-0.28	119	119
SMAD3/SMAD4/GR	-0.045	0.11	-10000	0	-0.26	96	96
GATA3	-0.002	0.065	-10000	0	-0.3	22	22
SKI/SIN3/HDAC complex/NCoR1	0.036	0.011	-10000	0	-10000	0	0
MEF2C/TIF2	-0.062	0.17	-10000	0	-0.45	68	68
endothelial cell migration	-0.015	0.13	1.2	5	-10000	0	5
MAX	0.009	0.005	-10000	0	-10000	0	0
RBBP7	0.011	0	-10000	0	-10000	0	0
RBBP4	0.009	0.027	-10000	0	-0.42	2	2
RUNX2	0.003	0.048	-10000	0	-0.28	14	14
RUNX3	0.002	0.048	-10000	0	-0.27	15	15
RUNX1	0.011	0	-10000	0	-10000	0	0
CTBP1	0.011	0	-10000	0	-10000	0	0
NR3C1	-0.069	0.17	-10000	0	-0.42	94	94
VDR	0.005	0.039	-10000	0	-0.27	10	10
CDKN1A	0.043	0.1	-10000	0	-1.2	3	3
KAT2B	0.002	0.059	-10000	0	-0.42	10	10
SMAD2/SMAD2/SMAD4/FOXH1	-0.028	0.089	-10000	0	-0.28	16	16
DCP1A	0.011	0	-10000	0	-10000	0	0
SKI	0.011	0	-10000	0	-10000	0	0
SERPINE1	0.014	0.13	-10000	0	-1.2	5	5
SMAD3/SMAD4/ATF2	0.013	0.05	-10000	0	-0.31	7	7
SMAD3/SMAD4/ATF3	-0.02	0.1	-10000	0	-0.27	70	70
SAP30	0.011	0	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.024	0.015	-10000	0	-0.23	1	1
JUN	-0.033	0.12	-10000	0	-0.44	14	14
SMAD3/SMAD4/IRF7	0.008	0.052	-10000	0	-0.28	8	8
TFE3	0.015	0.006	-10000	0	-10000	0	0
COL1A2	0.006	0.091	-10000	0	-0.82	5	5
mesenchymal cell differentiation	-0.008	0.054	0.25	12	-10000	0	12
DLX1	-0.027	0.091	-10000	0	-0.27	62	62
TCF3	0.011	0	-10000	0	-10000	0	0
FOS	-0.13	0.2	-10000	0	-0.42	174	174
SMAD3/SMAD4/Max	0.004	0.038	-10000	0	-0.27	5	5
Cbp/p300/SNIP1	0.022	0.012	-10000	0	-0.23	1	1
ZBTB17	0.009	0.001	-10000	0	-10000	0	0
LAMC1	0.031	0.037	-10000	0	-0.26	2	2
TGIF2/HDAC complex/SMAD3/SMAD4	0.014	0.041	-10000	0	-0.27	5	5
IRF7	0.005	0.043	-10000	0	-0.29	10	10
ESR1	-0.037	0.13	-10000	0	-0.42	56	56
HNF4A	-0.022	0.089	-10000	0	-0.28	56	56
MEF2C	-0.064	0.17	-10000	0	-0.47	64	64
SMAD2-3/SMAD4	0.016	0.049	-10000	0	-0.27	6	6
Cbp/p300/Src-1	0.022	0.017	-10000	0	-0.23	2	2
IGHV3OR16-13	-0.001	0.008	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.011	0	-10000	0	-10000	0	0
CREBBP	0.01	0.019	-10000	0	-0.42	1	1
SKIL	0.011	0	-10000	0	-10000	0	0
HDAC1	0.011	0	-10000	0	-10000	0	0
HDAC2	0.011	0	-10000	0	-10000	0	0
SNIP1	0.01	0.001	-10000	0	-10000	0	0
GCN5L2	0.001	0.003	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.029	0.044	-10000	0	-0.26	5	5
MSG1/HSC70	0.008	0.04	-10000	0	-0.19	19	19
SMAD2	0.007	0.019	-10000	0	-10000	0	0
SMAD3	0.009	0.048	-10000	0	-0.46	4	4
SMAD3/E2F4-5/DP1/p107/SMAD4	0.024	0.034	-10000	0	-0.22	5	5
SMAD2/SMAD2/SMAD4	0	0.046	-10000	0	-0.29	11	11
NCOR1	0.011	0	-10000	0	-10000	0	0
NCOA2	-0.004	0.079	-10000	0	-0.42	18	18
NCOA1	0.01	0.019	-10000	0	-0.42	1	1
MYOD/E2A	-0.006	0.054	-10000	0	-0.18	47	47
SMAD2-3/SMAD4/SP1/MIZ-1	0.04	0.052	-10000	0	-0.3	3	3
IFNB1	0.013	0.057	-10000	0	-0.29	9	9
SMAD3/SMAD4/MEF2C	-0.058	0.17	-10000	0	-0.46	63	63
CITED1	-0.001	0.059	-10000	0	-0.3	19	19
SMAD2-3/SMAD4/ARC105	0.022	0.045	-10000	0	-0.3	2	2
RBL1	0.011	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.039	0.037	-10000	0	-0.35	2	2
RUNX1-3/PEBPB2	0.017	0.027	-10000	0	-10000	0	0
SMAD7	-0.009	0.13	-10000	0	-0.47	13	13
MYC/MIZ-1	0.005	0.042	-10000	0	-0.29	10	10
SMAD3/SMAD4	0.009	0.06	-10000	0	-0.45	5	5
IL10	0.013	0.076	-10000	0	-0.4	4	4
PIASy/HDAC complex	0.01	0.003	-10000	0	-10000	0	0
PIAS3	0.011	0.001	-10000	0	-10000	0	0
CDK2	0.011	0.003	-10000	0	-10000	0	0
IL5	0.012	0.059	-10000	0	-0.31	6	6
CDK4	0.011	0.003	-10000	0	-10000	0	0
PIAS4	0.01	0.003	-10000	0	-10000	0	0
ATF3	-0.044	0.14	-10000	0	-0.42	66	66
SMAD3/SMAD4/SP1	0.03	0.052	-10000	0	-0.29	6	6
FOXG1	-0.12	0.14	-10000	0	-0.27	240	240
FOXO3	0.021	0.002	-10000	0	-10000	0	0
FOXO1	0.019	0.023	-10000	0	-0.28	3	3
FOXO4	0.02	0.019	-10000	0	-0.28	2	2
heart looping	-0.064	0.17	-10000	0	-0.46	64	64
CEBPB	0.012	0.001	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.007	0.072	-10000	0	-0.28	13	13
MYOD1	-0.021	0.08	-10000	0	-0.27	47	47
SMAD3/SMAD4/HNF4	-0.005	0.066	-10000	0	-0.31	7	7
SMAD3/SMAD4/GATA3	0.006	0.066	-10000	0	-0.34	7	7
SnoN/SIN3/HDAC complex/NCoR1	0.011	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.028	0.043	-10000	0	-0.24	3	3
SMAD3/SMAD4/SP1-3	0.038	0.049	-10000	0	-0.3	3	3
MED15	0.011	0	-10000	0	-10000	0	0
SP1	0.017	0.015	-10000	0	-0.17	1	1
SIN3B	0.011	0	-10000	0	-10000	0	0
SIN3A	0.011	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.028	0.13	-10000	0	-0.32	56	56
ITGB5	0.04	0.039	-10000	0	-0.28	2	2
TGIF/SIN3/HDAC complex/CtBP	0.036	0.011	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.033	0.11	-10000	0	-0.26	93	93
AR	-0.064	0.16	-10000	0	-0.42	90	90
negative regulation of cell growth	0.011	0.068	-10000	0	-0.3	6	6
SMAD3/SMAD4/MYOD	-0.004	0.061	-10000	0	-0.27	7	7
E2F5	0.011	0	-10000	0	-10000	0	0
E2F4	0.011	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.004	0.076	-10000	0	-0.23	15	15
SMAD2-3/SMAD4/FOXO1-3a-4	0.036	0.039	-10000	0	-0.36	2	2
TFDP1	0.011	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	-0.028	0.13	-10000	0	-0.45	14	14
SMAD3/SMAD4/RUNX2	0.01	0.055	-10000	0	-0.26	12	12
TGIF2	0.011	0	-10000	0	-10000	0	0
TGIF1	0.011	0	-10000	0	-10000	0	0
ATF2	0.008	0.033	-10000	0	-0.42	3	3

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.01	0.042	-10000	0	-0.29	10	10
ATM	0.011	0	-10000	0	-10000	0	0
UBE2D3	0.011	0	-10000	0	-10000	0	0
PRKDC	0.011	0	-10000	0	-10000	0	0
ATR	0.011	0	-10000	0	-10000	0	0
UBE2L3	0.011	0	-10000	0	-10000	0	0
FANCD2	0.02	0.005	-10000	0	-10000	0	0
protein ubiquitination	-0.048	0.057	-10000	0	-0.24	10	10
XRCC5	0.011	0	-10000	0	-10000	0	0
XRCC6	0.011	0	-10000	0	-10000	0	0
M/R/N Complex	0.022	0	-10000	0	-10000	0	0
MRE11A	0.011	0	-10000	0	-10000	0	0
DNA-PK	0.022	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.024	0.022	-10000	0	-10000	0	0
FANCF	0.009	0.027	-10000	0	-0.42	2	2
BRCA1	0.011	0	-10000	0	-10000	0	0
CCNE1	-0.11	0.14	-10000	0	-0.27	225	225
CDK2/Cyclin E1	-0.068	0.094	-10000	0	-0.18	225	225
FANCG	0.011	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.01	0.042	-10000	0	-0.29	10	10
FANCE	0.011	0	-10000	0	-10000	0	0
FANCC	0.011	0	-10000	0	-10000	0	0
NBN	0.011	0	-10000	0	-10000	0	0
FANCA	-0.048	0.12	-10000	0	-0.27	106	106
DNA repair	0.003	0.069	-10000	0	-0.28	7	7
BRCA1/BARD1/ubiquitin	0.01	0.042	-10000	0	-0.29	10	10
BARD1/DNA-PK	0.023	0.032	-10000	0	-0.2	10	10
FANCL	0.011	0	-10000	0	-10000	0	0
mRNA polyadenylation	-0.01	0.042	0.28	10	-10000	0	10
BRCA1/BARD1/CTIP/M/R/N Complex	0.027	0.03	-10000	0	-0.19	10	10
BRCA1/BACH1/BARD1/TopBP1	0.017	0.035	-10000	0	-0.23	10	10
BRCA1/BARD1/P53	0.022	0.034	-10000	0	-0.2	11	11
BARD1/CSTF1/BRCA1	0.017	0.035	-10000	0	-0.23	10	10
BRCA1/BACH1	0.011	0	-10000	0	-10000	0	0
BARD1	0.002	0.059	-10000	0	-0.42	10	10
PCNA	0.011	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	0.017	0.035	-10000	0	-0.23	10	10
BRCA1/BARD1/UbcH7	0.017	0.035	-10000	0	-0.23	10	10
BRCA1/BARD1/RAD51/PCNA	-0.013	0.072	-10000	0	-0.28	10	10
BARD1/DNA-PK/P53	0.027	0.031	-10000	0	-0.18	11	11
BRCA1/BARD1/Ubiquitin	0.01	0.042	-10000	0	-0.29	10	10
BRCA1/BARD1/CTIP	0.022	0.032	-10000	0	-0.2	10	10
FA complex	0.019	0.026	-10000	0	-0.22	1	1
BARD1/EWS	0.01	0.042	-10000	0	-0.29	10	10
RBBP8	0.017	0	-10000	0	-10000	0	0
TP53	0.01	0.019	-10000	0	-0.42	1	1
TOPBP1	0.011	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.021	0.033	0.2	11	-10000	0	11
BRCA1/BARD1	-0.031	0.073	-10000	0	-0.25	10	10
CSTF1	0.011	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.002	0.042	-10000	0	-0.29	10	10
CDK2	0.011	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.06	0.12	-10000	0	-0.27	128	128
RAD50	0.011	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.01	0.042	-10000	0	-0.29	10	10
EWSR1	0.011	0	-10000	0	-10000	0	0

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	-0.006	0.069	-10000	0	-0.29	29	29
PRKCZ	0.009	0.023	-10000	0	-0.34	2	2
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.011	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.003	0.025	-10000	0	-0.24	4	4
IRAK/TOLLIP	0.009	0.052	-10000	0	-0.2	29	29
IKBKB	0.011	0	-10000	0	-10000	0	0
IKBKG	0.011	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.011	0.072	-10000	0	-0.2	64	64
IL1A	-0.007	0.066	-10000	0	-0.27	30	30
IL1B	0.012	0.043	-10000	0	-0.32	8	8
IRAK/TRAF6/p62/Atypical PKCs	0.023	0.047	-10000	0	-0.35	1	1
IL1R2	-0.012	0.08	-10000	0	-0.29	39	39
IL1R1	0.004	0.053	-10000	0	-0.42	8	8
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.025	0.057	0.18	21	-0.26	10	31
TOLLIP	0.011	0	-10000	0	-10000	0	0
TICAM2	0.003	0.053	-10000	0	-0.42	8	8
MAP3K3	0.011	0	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.007	0	-10000	0	-10000	0	0
IKK complex/ELKS	0.039	0.041	-10000	0	-10000	0	0
JUN	0.005	0.063	-10000	0	-0.22	16	16
MAP3K7	0.011	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.026	0.052	-10000	0	-0.21	21	21
IL1 alpha/IL1R1/IL1RAP/MYD88	0.014	0.05	-10000	0	-0.24	10	10
PIK3R1	0.007	0.038	-10000	0	-0.42	4	4
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.019	0.046	-10000	0	-0.22	10	10
IL1 beta fragment/IL1R1/IL1RAP	0.017	0.048	-10000	0	-0.23	18	18
NFKB1	0.01	0.019	-10000	0	-0.42	1	1
MAPK8	0.002	0.062	-10000	0	-0.18	34	34
IRAK1	0.003	0.058	-10000	0	-0.23	29	29
IL1RN/IL1R1	-0.014	0.075	-10000	0	-0.19	74	74
IRAK4	0.011	0	-10000	0	-10000	0	0
PRKCI	0.011	0	-10000	0	-10000	0	0
TRAF6	0.011	0	-10000	0	-10000	0	0
PI3K	0.013	0.03	-10000	0	-0.29	5	5
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.024	0.042	-10000	0	-0.22	11	11
CHUK	0.011	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.017	0.048	-10000	0	-0.23	18	18
IL1 beta/IL1R2	0.004	0.059	-10000	0	-0.27	11	11
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.01	0.039	-10000	0	-0.17	29	29
NF kappa B1 p50/RelA	-0.008	0.041	-10000	0	-0.39	3	3
IRAK3	-0.009	0.088	-10000	0	-0.42	23	23
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.024	0.052	-10000	0	-0.37	3	3
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.021	0.037	-10000	0	-0.22	10	10
IL1 alpha/IL1R1/IL1RAP	0.007	0.054	-10000	0	-0.17	39	39
RELA	0.011	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.011	0	-10000	0	-10000	0	0
MYD88	0.011	0	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0.016	0.049	-10000	0	-0.18	29	29
IL1RAP	0.008	0.033	-10000	0	-0.42	3	3
UBE2N	0.011	0	-10000	0	-10000	0	0
IRAK/TRAF6	-0.015	0.05	-10000	0	-0.31	7	7
CASP1	0.006	0.042	-10000	0	-0.42	5	5
IL1RN/IL1R2	-0.024	0.085	-10000	0	-0.19	99	99
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.023	0.046	-10000	0	-0.21	18	18
TMEM189-UBE2V1	-0.02	0.097	-10000	0	-0.42	29	29
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.019	0.056	-10000	0	-0.35	8	8
PIK3CA	0.01	0.019	-10000	0	-0.42	1	1
IL1RN	-0.027	0.096	-10000	0	-0.27	68	68
TRAF6/TAK1/TAB1/TAB2	-0.01	0.042	-10000	0	-0.18	29	29
MAP2K6	-0.002	0.062	-10000	0	-0.19	29	29

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.01	0.012	-10000	0	-0.27	1	1
NFATC1	0.032	0.047	-10000	0	-0.26	12	12
NFATC2	0.004	0.055	-10000	0	-0.18	20	20
NFATC3	0.014	0.017	-10000	0	-0.32	1	1
YWHAE	0.011	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.01	0.093	-10000	0	-0.24	47	47
Exportin 1/Ran/NUP214	0.017	0.009	-10000	0	-10000	0	0
mol:DAG	-0.001	0.002	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.026	0.072	-10000	0	-0.34	16	16
BCL2/BAX	-0.012	0.088	-10000	0	-0.29	48	48
CaM/Ca2+/Calcineurin A alpha-beta B1	0.005	0.007	-10000	0	-10000	0	0
CaM/Ca2+	0.005	0.007	-10000	0	-10000	0	0
BAX	0.011	0	-10000	0	-10000	0	0
MAPK14	0.009	0.004	-10000	0	-10000	0	0
BAD	0.011	0	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.005	0.089	-10000	0	-0.35	17	17
Calcineurin A alpha-beta B1/BCL2	-0.029	0.12	-10000	0	-0.42	48	48
FKBP8	0.011	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.005	0.088	0.35	17	-10000	0	17
KPNB1	0.011	0	-10000	0	-10000	0	0
KPNA2	0.002	0.048	-10000	0	-0.27	15	15
XPO1	0.01	0.001	-10000	0	-10000	0	0
SFN	-0.21	0.12	-10000	0	-0.27	400	400
MAP3K8	0.004	0.042	-10000	0	-0.42	5	5
NFAT4/CK1 alpha	0.021	0.014	-10000	0	-0.16	1	1
MEF2D/NFAT1/Cbp/p300	-0.017	0.12	-10000	0	-0.23	112	112
CABIN1	-0.01	0.094	-10000	0	-0.24	47	47
CALM1	0.009	0.003	-10000	0	-10000	0	0
RAN	0.01	0.001	-10000	0	-10000	0	0
MAP3K1	0.011	0	-10000	0	-10000	0	0
CAMK4	0.006	0.038	-10000	0	-0.31	7	7
mol:Ca2+	-0.002	0.006	-10000	0	-10000	0	0
MAPK3	0.011	0	-10000	0	-10000	0	0
YWHAH	0.011	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.011	0.024	-10000	0	-0.29	3	3
YWHAB	0.011	0	-10000	0	-10000	0	0
MAPK8	0.004	0.042	-10000	0	-0.42	5	5
MAPK9	0.011	0	-10000	0	-10000	0	0
YWHAG	0.011	0	-10000	0	-10000	0	0
FKBP1A	0.011	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.036	0.049	-10000	0	-0.23	8	8
PRKCH	0.008	0.033	-10000	0	-0.42	3	3
CABIN1/Cbp/p300	0.011	0.017	-10000	0	-0.28	1	1
CASP3	0.009	0.004	-10000	0	-10000	0	0
PIM1	0.011	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.006	0.003	-10000	0	-10000	0	0
apoptosis	-0.008	0.024	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.011	0.011	-10000	0	-10000	0	0
PRKCB	-0.015	0.1	-10000	0	-0.42	31	31
PRKCE	0.011	0	-10000	0	-10000	0	0
JNK2/NFAT4	0.02	0.015	-10000	0	-0.28	1	1
BAD/BCL-XL	0.015	0.008	-10000	0	-0.18	1	1
PRKCD	0.011	0	-10000	0	-10000	0	0
NUP214	0.01	0.001	-10000	0	-10000	0	0
PRKCZ	0.007	0.023	-10000	0	-0.34	2	2
PRKCA	-0.017	0.1	-10000	0	-0.42	33	33
PRKCG	-0.031	0.1	-10000	0	-0.28	72	72
PRKCQ	-0.015	0.1	-10000	0	-0.41	31	31
FKBP38/BCL2	-0.012	0.088	-10000	0	-0.29	48	48
EP300	0.008	0.005	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.011	0	-10000	0	-10000	0	0
NFATc/JNK1	0.029	0.051	-10000	0	-0.24	12	12
CaM/Ca2+/FKBP38	0.012	0.006	-10000	0	-10000	0	0
FKBP12/FK506	0.008	0	-10000	0	-10000	0	0
CSNK1A1	0.011	0.009	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0.009	0.023	-10000	0	-0.17	7	7
NFATc/ERK1	0.037	0.045	-10000	0	-0.24	12	12
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.025	0.072	-10000	0	-0.32	17	17
NR4A1	-0.056	0.19	-10000	0	-0.41	112	112
GSK3B	0.009	0.005	-10000	0	-10000	0	0
positive T cell selection	0.014	0.017	-10000	0	-0.32	1	1
NFAT1/CK1 alpha	-0.016	0.034	-10000	0	-0.24	3	3
RCH1/ KPNB1	0.01	0.032	-10000	0	-0.18	15	15
YWHAQ	0.011	0	-10000	0	-10000	0	0
PRKACA	0.009	0.004	-10000	0	-10000	0	0
AKAP5	0.008	0.033	-10000	0	-0.42	3	3
MEF2D	0.008	0.005	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.011	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.031	0.047	-10000	0	-0.24	12	12
CREBBP	0.007	0.019	-10000	0	-0.42	1	1
BCL2	-0.029	0.12	-10000	0	-0.42	48	48

×

Retinoic acid receptors-mediated 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
HDAC1	0.011	0	-10000	0	-10000	0	0
HDAC3	0.011	0	-10000	0	-10000	0	0
VDR	0.005	0.039	-10000	0	-0.27	10	10
Cbp/p300/PCAF	0.016	0.037	-10000	0	-0.23	11	11
EP300	0.011	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.02	0.051	-10000	0	-0.28	7	7
KAT2B	0.002	0.059	-10000	0	-0.42	10	10
MAPK14	0.011	0	-10000	0	-10000	0	0
AKT1	0.012	0.058	0.19	19	-0.24	11	30
RAR alpha/9cRA/Cyclin H	-0.017	0.066	-10000	0	-0.24	33	33
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.016	0.056	-10000	0	-0.26	13	13
CDC2	0	0.001	-10000	0	-10000	0	0
response to UV	0.001	0.002	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.002	0.065	-10000	0	-0.24	20	20
NCOR2	0.011	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.004	0.026	-10000	0	-0.18	10	10
RXRs/RARs/NRIP1/9cRA	0.003	0.13	-10000	0	-0.41	39	39
NCOA2	-0.004	0.079	-10000	0	-0.42	18	18
NCOA3	0.01	0.012	-10000	0	-0.27	1	1
NCOA1	0.01	0.019	-10000	0	-0.42	1	1
VDR/VDR/DNA	0.005	0.039	-10000	0	-0.27	10	10
RARG	0.011	0.001	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.015	0.001	-10000	0	-10000	0	0
MAPK3	0.011	0.001	-10000	0	-10000	0	0
MAPK1	0.011	0	-10000	0	-10000	0	0
MAPK8	0.007	0.042	-10000	0	-0.42	5	5
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.002	0.12	-10000	0	-0.39	39	39
RARA	-0.002	0.07	-10000	0	-0.23	41	41
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.01	0.069	-10000	0	-0.28	18	18
PRKCA	-0.015	0.1	-10000	0	-0.42	33	33
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.006	0.14	-10000	0	-0.43	39	39
RXRG	-0.039	0.12	-10000	0	-0.3	80	80
RXRA	0.004	0.065	-10000	0	-0.21	41	41
RXRB	-0.009	0.083	-10000	0	-0.29	37	37
VDR/Vit D3/DNA	0.004	0.026	-10000	0	-0.18	10	10
RBP1	-0.007	0.085	-10000	0	-0.42	21	21
CRBP1/9-cic-RA	-0.004	0.06	-10000	0	-0.29	21	21
RARB	0.004	0.059	-10000	0	-0.42	10	10
PRKCG	-0.029	0.1	-10000	0	-0.28	72	72
MNAT1	0.011	0	-10000	0	-10000	0	0
RAR alpha/RXRs	0.003	0.13	-10000	0	-0.43	38	38
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.008	0.11	-10000	0	-0.34	37	37
proteasomal ubiquitin-dependent protein catabolic process	0.015	0.068	-10000	0	-0.35	8	8
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.006	0.14	-10000	0	-0.43	39	39
positive regulation of DNA binding	-0.016	0.062	-10000	0	-0.23	33	33
NRIP1	-0.006	0.15	-10000	0	-0.82	9	9
RXRs/RARs	-0.01	0.13	-10000	0	-0.42	40	40
RXRs/RXRs/DNA/9cRA	-0.009	0.12	-10000	0	-0.4	39	39
PRKACA	0.011	0	-10000	0	-10000	0	0
CDK7	0.011	0	-10000	0	-10000	0	0
TFIIH	0.022	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.009	0.039	-10000	0	-0.33	2	2
CCNH	0.011	0	-10000	0	-10000	0	0
CREBBP	0.01	0.019	-10000	0	-0.42	1	1
RAR gamma2/9cRA	0	0	-10000	0	-10000	0	0

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	-0.11	0.14	-9999	-0.27	225	225
mol:Halofuginone	0.004	0.001	-9999	-10000	0	0
ITGA1	0.008	0.033	-9999	-0.42	3	3
CDKN1A	0.005	0.053	-9999	-0.43	3	3
PRL-3/alpha Tubulin	0.016	0	-9999	-10000	0	0
mol:Ca2+	-0.043	0.1	-9999	-0.29	77	77
AGT	-0.052	0.15	-9999	-0.4	77	77
CCNA2	-0.04	0.098	-9999	-0.3	26	26
TUBA1B	0.011	0	-9999	-10000	0	0
EGR1	-0.032	0.11	-9999	-0.28	86	86
CDK2/Cyclin E1	0.027	0.087	-9999	-0.49	3	3
MAPK3	0.017	0	-9999	-10000	0	0
PRL-2 /Rab GGTase beta	0.016	0	-9999	-10000	0	0
MAPK1	0.017	0	-9999	-10000	0	0
PTP4A1	-0.01	0.084	-9999	-10000	0	0
PTP4A3	0.011	0	-9999	-10000	0	0
PTP4A2	0.011	0	-9999	-10000	0	0
ITGB1	0.017	0	-9999	-10000	0	0
SRC	0.011	0	-9999	-10000	0	0
RAC1	0.008	0.041	-9999	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0.016	0	-9999	-10000	0	0
PRL-1/ATF-5	-0.005	0.08	-9999	-0.3	1	1
RABGGTA	0.011	0	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
RHOC	0.008	0.041	-9999	-10000	0	0
RHOA	0.008	0.041	-9999	-10000	0	0
cell motility	0.01	0.044	-9999	-10000	0	0
PRL-1/alpha Tubulin	-0.004	0.078	-9999	-10000	0	0
PRL-3/alpha1 Integrin	0.014	0.023	-9999	-0.29	3	3
ROCK1	0.01	0.044	-9999	-10000	0	0
RABGGTB	0.011	0	-9999	-10000	0	0
CDK2	0.011	0	-9999	-10000	0	0
mitosis	-0.01	0.084	-9999	-10000	0	0
ATF5	0.008	0.025	-9999	-0.27	4	4

×

JNK signaling in the CD4+ TCR pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.015	0.051	-9999	-0.21	21	21
MAP4K1	0.004	0.043	-9999	-0.27	12	12
MAP3K8	0.006	0.042	-9999	-0.42	5	5
PRKCB	-0.015	0.1	-9999	-0.42	31	31
DBNL	0.011	0	-9999	-10000	0	0
CRKL	0.011	0	-9999	-10000	0	0
MAP3K1	0.026	0.041	-9999	-0.21	1	1
JUN	-0.012	0.14	-9999	-0.53	36	36
MAP3K7	0.026	0.041	-9999	-0.18	20	20
GRAP2	-0.006	0.083	-9999	-0.42	20	20
CRK	0.011	0	-9999	-10000	0	0
MAP2K4	0.03	0.043	-9999	-0.2	1	1
LAT	0.011	0	-9999	-10000	0	0
LCP2	0.01	0.012	-9999	-0.27	1	1
MAPK8	-0.016	0.15	-9999	-0.55	36	36
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.022	0.044	-9999	-0.19	20	20
LAT/GRAP2/SLP76/HPK1/HIP-55	0.02	0.048	-9999	-0.19	21	21

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.027	0.023	-9999	-10000	0	0
PLK1	-0.049	0.17	-9999	-0.52	23	23
CDKN1B	0.016	0.13	-9999	-0.44	24	24
FOXO3	-0.025	0.17	-9999	-0.46	55	55
KAT2B	-0.002	0.061	-9999	-0.42	10	10
FOXO1/SIRT1	0.021	0.028	-9999	-10000	0	0
CAT	-0.016	0.16	-9999	-0.68	4	4
CTNNB1	0.011	0	-9999	-10000	0	0
AKT1	0.009	0.016	-9999	-10000	0	0
FOXO1	0.027	0.024	-9999	-0.23	4	4
MAPK10	-0.022	0.093	-9999	-0.19	115	115
mol:GTP	0.002	0.001	-9999	-10000	0	0
FOXO4	0.035	0.078	-9999	-0.32	5	5
response to oxidative stress	-0.001	0.017	-9999	-10000	0	0
FOXO3A/SIRT1	-0.06	0.14	-9999	-0.41	67	67
XPO1	0.011	0	-9999	-10000	0	0
EP300	0.012	0.001	-9999	-10000	0	0
BCL2L11	0.015	0.024	-9999	-10000	0	0
FOXO1/SKP2	0.029	0.022	-9999	-10000	0	0
mol:GDP	-0.001	0.017	-9999	-10000	0	0
RAN	0.012	0	-9999	-10000	0	0
GADD45A	0.021	0.093	-9999	-0.46	2	2
YWHAQ	0.011	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.04	0.011	-9999	-10000	0	0
MST1	0.001	0.043	-9999	-0.28	10	10
CSNK1D	0.011	0	-9999	-10000	0	0
CSNK1E	0.011	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.029	0.01	-9999	-10000	0	0
YWHAB	0.011	0	-9999	-10000	0	0
MAPK8	0.024	0.023	-9999	-0.2	5	5
MAPK9	0.026	0.008	-9999	-10000	0	0
YWHAG	0.011	0	-9999	-10000	0	0
YWHAE	0.011	0	-9999	-10000	0	0
YWHAZ	0.011	0	-9999	-10000	0	0
SIRT1	0.008	0.027	-9999	-0.41	2	2
SOD2	0.033	0.11	-9999	-0.43	3	3
RBL2	0.002	0.14	-9999	-0.77	5	5
RAL/GDP	0.018	0.01	-9999	-10000	0	0
CHUK	0.007	0.015	-9999	-10000	0	0
Ran/GTP	0.011	0.001	-9999	-10000	0	0
CSNK1G2	0.011	0	-9999	-10000	0	0
RAL/GTP	0.023	0.011	-9999	-10000	0	0
CSNK1G1	0.011	0	-9999	-10000	0	0
FASLG	0.005	0.1	-9999	-1.3	3	3
SKP2	0.011	0	-9999	-10000	0	0
USP7	0.012	0	-9999	-10000	0	0
IKBKB	0.007	0.015	-9999	-10000	0	0
CCNB1	-0.025	0.16	-9999	-0.52	22	22
FOXO1-3a-4/beta catenin	0.044	0.11	-9999	-0.36	7	7
proteasomal ubiquitin-dependent protein catabolic process	0.029	0.022	-9999	-10000	0	0
CSNK1A1	0.011	0	-9999	-10000	0	0
SGK1	0.004	0.037	-9999	-0.44	3	3
CSNK1G3	0.011	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.02	0.002	-9999	-10000	0	0
ZFAND5	0.04	0.068	-9999	-10000	0	0
SFN	-0.21	0.12	-9999	-0.27	400	400
CDK2	0.012	0.002	-9999	-10000	0	0
FOXO3A/14-3-3	0.02	0.031	-9999	-10000	0	0
CREBBP	0.011	0.019	-9999	-0.42	1	1
FBXO32	-0.11	0.4	-9999	-1.2	64	64
BCL6	0.004	0.13	-9999	-0.68	4	4
RALB	0.012	0	-9999	-10000	0	0
RALA	0.012	0	-9999	-10000	0	0
YWHAH	0.011	0	-9999	-10000	0	0

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.008	0.061	-10000	0	-0.42	8	8
FYN	0.036	0.092	-10000	0	-0.48	10	10
LAT/GRAP2/SLP76	-0.008	0.076	-10000	0	-0.37	15	15
IKBKB	0.011	0	-10000	0	-10000	0	0
AKT1	0.039	0.07	-10000	0	-0.3	15	15
B2M	0.012	0.002	-10000	0	-10000	0	0
IKBKG	-0.003	0.016	-10000	0	-0.12	5	5
MAP3K8	0.006	0.042	-10000	0	-0.42	5	5
mol:Ca2+	-0.009	0.022	-10000	0	-0.073	47	47
integrin-mediated signaling pathway	0.014	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.039	0.096	-10000	0	-0.4	16	16
TRPV6	-0.047	0.12	-10000	0	-0.34	72	72
CD28	0.01	0.018	-10000	0	-0.27	2	2
SHC1	0.036	0.087	-10000	0	-0.49	9	9
receptor internalization	0.03	0.079	-10000	0	-0.42	10	10
PRF1	0.023	0.13	-10000	0	-1.1	6	6
KRAS	0.01	0.012	-10000	0	-0.27	1	1
GRB2	0.011	0	-10000	0	-10000	0	0
COT/AKT1	0.038	0.061	-10000	0	-0.25	14	14
LAT	0.036	0.087	-10000	0	-0.49	9	9
EntrezGene:6955	0.001	0.002	-10000	0	-10000	0	0
CD3D	-0.002	0.068	-10000	0	-0.32	21	21
CD3E	0.004	0.057	-10000	0	-0.37	11	11
CD3G	0.007	0.039	-10000	0	-0.35	6	6
RASGRP2	-0.014	0.06	-10000	0	-0.16	74	74
RASGRP1	0.042	0.076	-10000	0	-0.32	14	14
HLA-A	0.011	0.013	-10000	0	-0.27	1	1
RASSF5	0.011	0	-10000	0	-10000	0	0
RAP1A/GTP/RAPL	0.014	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.023	0.033	-10000	0	-0.11	11	11
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.006	0.029	-10000	0	-0.17	10	10
PRKCA	-0.004	0.044	-10000	0	-0.19	16	16
GRAP2	-0.006	0.083	-10000	0	-0.42	20	20
mol:IP3	0.008	0.077	0.16	58	-0.3	12	70
EntrezGene:6957	0.001	0.002	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	0.021	0.075	-10000	0	-0.5	7	7
ORAI1	0.03	0.073	0.21	72	-10000	0	72
CSK	0.034	0.089	-10000	0	-0.5	9	9
B7 family/CD28	0.038	0.087	-10000	0	-0.42	12	12
CHUK	0.011	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	0.031	0.1	-10000	0	-0.46	13	13
PTPN6	0.033	0.089	-10000	0	-0.5	9	9
VAV1	0.034	0.091	-10000	0	-0.49	10	10
Monovalent TCR/CD3	0.013	0.055	-10000	0	-0.27	15	15
CBL	0.011	0	-10000	0	-10000	0	0
LCK	0.033	0.096	-10000	0	-0.48	11	11
PAG1	0.034	0.092	-10000	0	-0.49	10	10
RAP1A	0.011	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	0.03	0.098	-10000	0	-0.56	9	9
CD80	0	0.053	-10000	0	-0.27	19	19
CD86	0.01	0.018	-10000	0	-0.28	2	2
PDK1/CARD11/BCL10/MALT1	-0.007	0.035	-10000	0	-0.2	11	11
HRAS	0.011	0	-10000	0	-10000	0	0
GO:0035030	0.034	0.075	-10000	0	-0.36	12	12
CD8A	0.003	0.059	-10000	0	-0.37	12	12
CD8B	-0.007	0.076	-10000	0	-0.3	31	31
PTPRC	0.001	0.063	-10000	0	-0.41	12	12
PDK1/PKC theta	0.043	0.087	-10000	0	-0.37	14	14
CSK/PAG1	0.036	0.089	-10000	0	-0.48	10	10
SOS1	0.011	0	-10000	0	-10000	0	0
peptide-MHC class I	0.018	0.009	-10000	0	-0.17	1	1
GRAP2/SLP76	-0.01	0.088	-10000	0	-0.43	15	15
STIM1	0.014	0.035	-10000	0	-10000	0	0
RAS family/GTP	0.04	0.033	-10000	0	-0.16	5	5
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	0.03	0.083	-10000	0	-0.47	9	9
mol:DAG	-0.003	0.054	-10000	0	-0.27	13	13
RAP1A/GDP	0.011	0.015	-10000	0	-0.053	7	7
PLCG1	0.011	0	-10000	0	-10000	0	0
CD247	0.01	0.023	-10000	0	-0.35	2	2
cytotoxic T cell degranulation	0.024	0.12	-10000	0	-1	6	6
RAP1A/GTP	-0.009	0.02	-10000	0	-0.058	74	74
mol:PI-3-4-5-P3	0.039	0.082	-10000	0	-0.34	16	16
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.006	0.091	0.18	56	-0.38	12	68
NRAS	0.011	0	-10000	0	-10000	0	0
ZAP70	0	0.056	-10000	0	-0.29	18	18
GRB2/SOS1	0.016	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.009	0.073	-10000	0	-0.35	16	16
MALT1	0.011	0	-10000	0	-10000	0	0
TRAF6	0.011	0	-10000	0	-10000	0	0
CD8 heterodimer	0	0.07	-10000	0	-0.23	39	39
CARD11	0.003	0.049	-10000	0	-0.29	13	13
PRKCB	-0.007	0.056	-10000	0	-0.23	23	23
PRKCE	-0.002	0.039	-10000	0	-0.2	12	12
PRKCQ	0.038	0.096	-10000	0	-0.42	14	14
LCP2	0.01	0.012	-10000	0	-0.27	1	1
BCL10	0.011	0	-10000	0	-10000	0	0
regulation of survival gene product expression	0.038	0.062	-10000	0	-0.25	15	15
IKK complex	0.029	0.035	-10000	0	-0.093	15	15
RAS family/GDP	-0.001	0.004	-10000	0	-10000	0	0
MAP3K14	0.038	0.049	-10000	0	-0.2	11	11
PDPK1	0.04	0.068	-10000	0	-0.29	14	14
TCR/CD3/MHC I/CD8/Fyn	0.025	0.11	-10000	0	-0.58	12	12

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.011	0.02	0.18	1	-10000	0	1
AES	0.011	0.017	0.16	1	-10000	0	1
FBXW11	0.011	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.015	0.014	-10000	0	-0.29	1	1
SMAD4	0.01	0.019	-10000	0	-0.42	1	1
DKK2	-0.021	0.11	-10000	0	-0.4	39	39
TLE1	0.01	0.025	0.16	1	-0.42	1	2
MACF1	0.011	0	-10000	0	-10000	0	0
CTNNB1	0.035	0.04	0.21	4	-10000	0	4
WIF1	-0.081	0.14	-10000	0	-0.29	155	155
beta catenin/RanBP3	0.02	0.09	0.36	33	-10000	0	33
KREMEN2	-0.017	0.084	-10000	0	-0.27	50	50
DKK1	-0.051	0.12	-10000	0	-0.28	108	108
beta catenin/beta TrCP1	0.04	0.038	0.2	4	-10000	0	4
FZD1	0.01	0.019	-10000	0	-0.42	1	1
AXIN2	-0.051	0.28	-10000	0	-1.3	25	25
AXIN1	0.011	0	-10000	0	-10000	0	0
RAN	0.011	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.013	0.021	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.045	0.053	0.22	1	-0.33	5	6
Axin1/APC/GSK3	0.017	0.027	0.18	2	-10000	0	2
Axin1/APC/GSK3/beta catenin/Macf1	0.041	0.021	-10000	0	-10000	0	0
HNF1A	-0.005	0.068	0.16	1	-0.27	29	30
CTBP1	0.011	0.017	0.17	1	-10000	0	1
MYC	-0.018	0.19	-10000	0	-1.3	10	10
RANBP3	0.011	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.013	0.082	-10000	0	-0.25	38	38
NKD1	-0.016	0.088	-10000	0	-0.3	44	44
TCF4	-0.005	0.081	0.16	1	-0.41	19	20
TCF3	0.011	0.017	0.16	1	-10000	0	1
WNT1/LRP6/FZD1/Axin1	0.024	0.021	-10000	0	-0.21	1	1
Ran/GTP	0.008	0.002	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.019	0.11	0.44	27	-0.4	2	29
LEF1	0.006	0.045	0.16	1	-0.37	6	7
DVL1	0.03	0.016	-10000	0	-10000	0	0
CSNK2A1	0.011	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.041	0.076	-10000	0	-0.34	10	10
DKK1/LRP6/Kremen 2	-0.028	0.078	-10000	0	-0.26	10	10
LRP6	0.011	0	-10000	0	-10000	0	0
CSNK1A1	0.012	0.02	0.18	1	-10000	0	1
NLK	0.011	0.003	-10000	0	-10000	0	0
CCND1	0.003	0.055	-10000	0	-10000	0	0
WNT1	0.004	0.035	-10000	0	-0.27	8	8
GSK3A	0.011	0	-10000	0	-10000	0	0
GSK3B	0.011	0	-10000	0	-10000	0	0
FRAT1	0.011	0	-10000	0	-10000	0	0
PPP2R5D	0.027	0.041	0.25	8	-10000	0	8
APC	0.027	0.019	-10000	0	-0.18	1	1
WNT1/LRP6/FZD1	0.031	0.046	0.2	18	-0.19	1	19
CREBBP	0.01	0.024	0.16	1	-0.38	1	2

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.12	0.1	-9999	-0.46	2	2
RAD9A	0.011	0	-9999	-10000	0	0
AP1	-0.093	0.15	-9999	-0.3	174	174
IFNAR2	0.009	0.019	-9999	-0.42	1	1
AKT1	-0.012	0.056	-9999	-10000	0	0
ER alpha/Oestrogen	-0.027	0.093	-9999	-0.29	56	56
NFX1/SIN3/HDAC complex	0.033	0.012	-9999	-10000	0	0
EGF	-0.002	0.058	-9999	-0.29	20	20
SMG5	0.011	0	-9999	-10000	0	0
SMG6	0.011	0	-9999	-10000	0	0
SP3/HDAC2	0.01	0.009	-9999	-10000	0	0
TERT/c-Abl	-0.11	0.097	-9999	-0.44	4	4
SAP18	0.01	0.001	-9999	-10000	0	0
MRN complex	0.022	0	-9999	-10000	0	0
WT1	-0.31	0.18	-9999	-0.42	386	386
WRN	0.011	0	-9999	-10000	0	0
SP1	0.007	0.006	-9999	-10000	0	0
SP3	0.01	0.001	-9999	-10000	0	0
TERF2IP	0.011	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.096	0.076	-9999	-0.44	1	1
Mad/Max	0.01	0.009	-9999	-10000	0	0
TERT	-0.12	0.1	-9999	-0.46	2	2
CCND1	-0.1	0.095	-9999	-10000	0	0
MAX	0.01	0.001	-9999	-10000	0	0
RBBP7	0.01	0.001	-9999	-10000	0	0
RBBP4	0.009	0.027	-9999	-0.42	2	2
TERF2	0.01	0	-9999	-10000	0	0
PTGES3	0.011	0	-9999	-10000	0	0
SIN3A	0.01	0.001	-9999	-10000	0	0
Telomerase/911	0.008	0.018	-9999	-10000	0	0
CDKN1B	-0.003	0.11	-9999	-0.51	20	20
RAD1	0.011	0	-9999	-10000	0	0
XRCC5	0.011	0	-9999	-10000	0	0
XRCC6	0.011	0	-9999	-10000	0	0
SAP30	0.01	0.001	-9999	-10000	0	0
TRF2/PARP2	0.016	0	-9999	-10000	0	0
UBE3A	0.01	0.001	-9999	-10000	0	0
JUN	0.005	0.046	-9999	-0.42	6	6
E6	-0.001	0.001	-9999	-10000	0	0
HPV-16 E6/E6AP	0.005	0.005	-9999	-10000	0	0
FOS	-0.14	0.2	-9999	-0.42	174	174
IFN-gamma/IRF1	-0.008	0.067	-9999	-0.26	20	20
PARP2	0.011	0	-9999	-10000	0	0
BLM	-0.013	0.078	-9999	-0.27	43	43
Telomerase	-0.008	0.027	-9999	-10000	0	0
IRF1	0.008	0.032	-9999	-10000	0	0
ESR1	-0.036	0.13	-9999	-0.42	56	56
KU/TER	0.016	0	-9999	-10000	0	0
ATM/TRF2	0.017	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.037	0.012	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.037	0.012	-9999	-10000	0	0
HDAC1	0.01	0.001	-9999	-10000	0	0
HDAC2	0.009	0.004	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.015	0.03	-9999	-0.29	5	5
ABL1	0.009	0.027	-9999	-0.42	2	2
MXD1	0.01	0.001	-9999	-10000	0	0
MRE11A	0.011	0	-9999	-10000	0	0
HUS1	0.011	0	-9999	-10000	0	0
RPS6KB1	0.011	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.087	0.08	-9999	-0.41	1	1
NR2F2	-0.005	0.083	-9999	-0.42	20	20
MAPK3	0.005	0.034	-9999	-0.18	17	17
MAPK1	0.005	0.034	-9999	-0.18	17	17
TGFB1/TGF beta receptor Type II	0.01	0.019	-9999	-0.42	1	1
NFKB1	0.01	0.019	-9999	-0.42	1	1
HNRNPC	0.011	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0	0	-9999	-10000	0	0
NBN	0.011	0	-9999	-10000	0	0
EGFR	-0.001	0.068	-9999	-0.41	14	14
mol:Oestrogen	0	0.001	-9999	-10000	0	0
EGF/EGFR	-0.001	0.063	-9999	-0.23	33	33
MYC	0.002	0.059	-9999	-0.42	10	10
IL2	-0.007	0.05	-9999	-0.27	17	17
KU	0.016	0	-9999	-10000	0	0
RAD50	0.011	0	-9999	-10000	0	0
HSP90AA1	0.011	0	-9999	-10000	0	0
TGFB1	0.01	0.019	-9999	-0.42	1	1
TRF2/BLM	0.001	0.048	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.1	0.096	-9999	-0.48	1	1
SP1/HDAC2	0.012	0.01	-9999	-10000	0	0
PINX1	0.011	0	-9999	-10000	0	0
Telomerase/EST1A	-0.096	0.076	-9999	-0.44	1	1
Smad3/Myc	0.014	0.045	-9999	-0.25	14	14
911 complex	0.022	0	-9999	-10000	0	0
IFNG	-0.012	0.072	-9999	-0.26	31	31
Telomerase/PinX1	-0.096	0.076	-9999	-0.44	1	1
Telomerase/AKT1/mTOR/p70S6K	-0.013	0.036	-9999	-10000	0	0
SIN3B	0.01	0.001	-9999	-10000	0	0
YWHAE	0.011	0	-9999	-10000	0	0
Telomerase/EST1B	-0.096	0.076	-9999	-0.44	1	1
response to DNA damage stimulus	0.003	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0.031	0	-9999	-10000	0	0
TRF2/WRN	0.016	0	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.096	0.076	-9999	-0.44	1	1
E2F1	-0.051	0.12	-9999	-0.27	109	109
ZNFX1	0.01	0.001	-9999	-10000	0	0
PIF1	-0.058	0.12	-9999	-0.27	124	124
NCL	0.011	0	-9999	-10000	0	0
DKC1	0.011	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.011	0	-9999	-10000	0	0
SPHK1	0.01	0.018	-9999	-0.27	2	2
GNAI2	0.011	0	-9999	-10000	0	0
mol:S1P	0.017	0.003	-9999	-10000	0	0
GNAO1	-0.098	0.19	-9999	-0.42	131	131
mol:Sphinganine-1-P	0.017	0.012	-9999	-0.18	2	2
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.031	0.002	-9999	-10000	0	0
GNAI3	0.011	0	-9999	-10000	0	0
G12/G13	0.016	0	-9999	-10000	0	0
S1PR3	-0.004	0.076	-9999	-0.42	17	17
S1PR2	0.011	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	0	0.002	-9999	-10000	0	0
S1PR5	0.002	0.05	-9999	-0.28	15	15
S1PR4	0.009	0.023	-9999	-0.34	2	2
GNAI1	0.002	0.059	-9999	-0.42	10	10
S1P/S1P5/G12	0.021	0.025	-9999	-0.2	1	1
S1P/S1P3/Gq	-0.009	0.1	-9999	-0.26	57	57
S1P/S1P4/Gi	-0.037	0.12	-9999	-0.39	17	17
GNAQ	0.009	0.027	-9999	-0.42	2	2
GNAZ	-0.011	0.094	-9999	-0.42	26	26
GNA14	-0.034	0.13	-9999	-0.42	53	53
GNA15	0.007	0.033	-9999	-0.27	7	7
GNA12	0.011	0	-9999	-10000	0	0
GNA13	0.011	0	-9999	-10000	0	0
GNA11	0.001	0.062	-9999	-0.42	11	11
ABCC1	0.011	0	-9999	-10000	0	0

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.072	0.089	-9999	-0.28	1	1
CaM/Ca2+	0.008	0	-9999	-10000	0	0
AKT1	0.011	0	-9999	-10000	0	0
AKT2	0.011	0	-9999	-10000	0	0
STXBP4	0.01	0.019	-9999	-0.42	1	1
mol:GTP	0	0	-9999	-10000	0	0
mol:glucose	-0.078	0.1	-9999	-0.31	1	1
YWHAZ	0.011	0	-9999	-10000	0	0
CALM1	0.011	0	-9999	-10000	0	0
YWHAQ	0.011	0	-9999	-10000	0	0
TBC1D4	0.015	0.027	-9999	-0.29	4	4
mol:Ca2+	0	0	-9999	-10000	0	0
YWHAH	0.011	0	-9999	-10000	0	0
YWHAB	0.011	0	-9999	-10000	0	0
SNARE/Synip	0.021	0.016	-9999	-0.23	2	2
YWHAG	0.011	0	-9999	-10000	0	0
ASIP	0.007	0.013	-9999	-0.27	1	1
PRKCI	0.011	0	-9999	-10000	0	0
AS160/CaM/Ca2+	0.008	0	-9999	-10000	0	0
RHOQ	0.011	0	-9999	-10000	0	0
GYS1	0.024	0	-9999	-10000	0	0
PRKCZ	0.009	0.023	-9999	-0.34	2	2
TRIP10	0.011	0	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.014	0	-9999	-10000	0	0
AS160/14-3-3	0.012	0.018	-9999	-10000	0	0
VAMP2	0.01	0.019	-9999	-0.42	1	1
SLC2A4	-0.085	0.11	-9999	-0.34	1	1
STX4	0.011	0	-9999	-10000	0	0
GSK3B	0.02	0	-9999	-10000	0	0
SFN	-0.21	0.12	-9999	-0.27	400	400
LNPEP	0.011	0	-9999	-10000	0	0
YWHAE	0.011	0	-9999	-10000	0	0

×

mTOR 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
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.011	0	-10000	0	-10000	0	0
mol:PIP3	-0.022	0.079	0.23	5	-0.25	49	54
FRAP1	0.008	0.018	-10000	0	-10000	0	0
AKT1	0.001	0.071	0.2	5	-0.21	49	54
INSR	0.011	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.008	0.002	-10000	0	-10000	0	0
mol:GTP	-0.015	0.048	-10000	0	-0.16	46	46
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.004	0.014	-10000	0	-10000	0	0
TSC2	0.011	0	-10000	0	-10000	0	0
RHEB/GDP	-0.013	0.04	-10000	0	-0.28	2	2
TSC1	0.01	0.019	-10000	0	-0.42	1	1
Insulin Receptor/IRS1	-0.016	0.091	-10000	0	-0.3	47	47
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.005	0.017	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.011	0	-10000	0	-10000	0	0
RPS6KB1	0.011	0.04	0.16	5	-0.22	2	7
MAP3K5	0.006	0.026	-10000	0	-0.33	3	3
PIK3R1	0.007	0.038	-10000	0	-0.42	4	4
apoptosis	0.006	0.025	-10000	0	-0.33	3	3
mol:LY294002	0	0	-10000	0	-0.001	47	47
EIF4B	0.016	0.037	0.16	5	-0.19	2	7
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.017	0.032	-10000	0	-0.18	2	2
eIF4E/eIF4G1/eIF4A1	-0.001	0.004	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	-0.008	0.088	-10000	0	-0.27	50	50
mTOR/RHEB/GTP/Raptor/GBL	0.017	0.028	0.15	5	-0.14	3	8
FKBP1A	0.011	0	-10000	0	-10000	0	0
RHEB/GTP	-0.013	0.04	-10000	0	-0.27	2	2
mol:Amino Acids	0	0	-10000	0	-0.001	47	47
FKBP12/Rapamycin	0.008	0.001	-10000	0	-10000	0	0
PDPK1	-0.02	0.071	0.21	5	-0.23	49	54
EIF4E	0.011	0	-10000	0	-10000	0	0
ASK1/PP5C	0.012	0.047	-10000	0	-0.58	3	3
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.013	0.002	-10000	0	-10000	0	0
TSC1/TSC2	0.011	0.06	-10000	0	-0.17	46	46
tumor necrosis factor receptor activity	0	0	0.001	47	-10000	0	47
RPS6	0.011	0	-10000	0	-10000	0	0
PPP5C	0.011	0	-10000	0	-10000	0	0
EIF4G1	0.011	0	-10000	0	-10000	0	0
IRS1	-0.024	0.096	-10000	0	-0.33	47	47
INS	0.001	0.002	-10000	0	-10000	0	0
PTEN	0.005	0.046	-10000	0	-0.42	6	6
PDK2	-0.02	0.071	0.21	5	-0.23	49	54
EIF4EBP1	0.012	0.013	-10000	0	-10000	0	0
PIK3CA	0.01	0.019	-10000	0	-0.42	1	1
PPP2R5D	0.013	0.017	-10000	0	-10000	0	0
peptide biosynthetic process	0.014	0.001	-10000	0	-10000	0	0
RHEB	0.011	0	-10000	0	-10000	0	0
EIF4A1	0.011	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	0.003	6	-0.002	5	11
EEF2	0.014	0.001	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.017	0.009	-10000	0	-10000	0	0

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.031	0.036	-10000	0	-0.17	12	12
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	0.011	0	-10000	0	-10000	0	0
STAT1 (dimer)/Cbp/p300	0.043	0.037	-10000	0	-10000	0	0
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.016	0.039	-10000	0	-0.23	12	12
antigen processing and presentation of peptide antigen via MHC class I	-0.033	0.04	-10000	0	-0.22	7	7
CaM/Ca2+	0.002	0.033	-10000	0	-0.16	4	4
RAP1A	0.011	0	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	0.025	0.039	-10000	0	-0.19	1	1
AKT1	0.029	0.041	-10000	0	-0.28	2	2
MAP2K1	0.03	0.036	-10000	0	-10000	0	0
MAP3K11	0.023	0.038	-10000	0	-10000	0	0
IFNGR1	0.011	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.18	0.17	-10000	0	-0.32	281	281
Rap1/GTP	-0.005	0.019	-10000	0	-10000	0	0
CRKL/C3G	0.016	0	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.032	0.037	-10000	0	-0.18	12	12
CEBPB	0.051	0.043	-10000	0	-0.38	2	2
STAT3	0.011	0	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.034	0.059	-10000	0	-1	1	1
STAT1	0.024	0.038	-10000	0	-0.19	1	1
CALM1	0.011	0	-10000	0	-10000	0	0
IFN-gamma (dimer)	-0.007	0.066	-10000	0	-0.27	31	31
PIK3CA	0.01	0.019	-10000	0	-0.42	1	1
STAT1 (dimer)/PIAS1	0.029	0.037	-10000	0	-0.18	1	1
CEBPB/PTGES2/Cbp/p300	-0.002	0.019	-10000	0	-0.24	2	2
mol:Ca2+	0.029	0.035	-10000	0	-0.17	12	12
MAPK3	0.037	0.035	-10000	0	-10000	0	0
STAT1 (dimer)	-0.038	0.058	-10000	0	-0.3	7	7
MAPK1	0.037	0.035	-10000	0	-10000	0	0
JAK2	0.004	0.056	-10000	0	-0.42	9	9
PIK3R1	0.007	0.038	-10000	0	-0.42	4	4
JAK1	0.009	0.033	-10000	0	-0.41	3	3
CAMK2D	0.009	0.027	-10000	0	-0.42	2	2
DAPK1	0.048	0.047	-10000	0	-0.58	2	2
SMAD7	0.002	0.04	-10000	0	-0.3	1	1
CBL/CRKL/C3G	0.032	0.035	-10000	0	-10000	0	0
PI3K	-0.001	0.037	-10000	0	-0.3	2	2
IFNG	-0.007	0.066	-10000	0	-0.27	31	31
apoptosis	0.029	0.038	-10000	0	-0.43	2	2
CAMK2G	0.011	0	-10000	0	-10000	0	0
STAT3 (dimer)	0.011	0	-10000	0	-10000	0	0
CAMK2A	-0.22	0.21	-10000	0	-0.42	281	281
CAMK2B	-0.045	0.11	-10000	0	-0.27	100	100
FRAP1	0.028	0.039	-10000	0	-0.26	2	2
PRKCD	0.031	0.041	-10000	0	-0.28	2	2
RAP1B	0.011	0	-10000	0	-10000	0	0
negative regulation of cell growth	-0.033	0.04	-10000	0	-0.22	7	7
PTPN2	0.011	0	-10000	0	-10000	0	0
EP300	0.011	0	-10000	0	-10000	0	0
IRF1	0.048	0.034	-10000	0	-0.26	1	1
STAT1 (dimer)/PIASy	0.026	0.037	0.17	1	-10000	0	1
SOCS1	-0.001	0.056	-10000	0	-1.3	1	1
mol:GDP	-0.006	0.024	-10000	0	-10000	0	0
CASP1	0	0.044	-10000	0	-0.23	6	6
PTGES2	0.01	0.019	-10000	0	-0.42	1	1
IRF9	0.041	0.017	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.009	0.033	-10000	0	-0.29	2	2
RAP1/GDP	-0.005	0.019	-10000	0	-10000	0	0
CBL	0.023	0.037	-10000	0	-0.16	4	4
MAP3K1	0.024	0.038	-10000	0	-10000	0	0
PIAS1	0.011	0	-10000	0	-10000	0	0
PIAS4	0.01	0	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.033	0.04	-10000	0	-0.22	7	7
PTPN11	0.017	0.039	-10000	0	-0.17	12	12
CREBBP	0.01	0.019	-10000	0	-0.42	1	1
RAPGEF1	0.011	0	-10000	0	-10000	0	0

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.038	0.04	-9999	-0.55	1	1
UGCG	0.005	0.093	-9999	-0.64	10	10
AKT1/mTOR/p70S6K/Hsp90/TERT	0.025	0.097	-9999	-0.24	46	46
mol:GTP	0	0	-9999	-10000	0	0
mol:glucosylceramide	0.005	0.092	-9999	-0.63	10	10
mol:DAG	0	0.001	-9999	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.039	0.11	-9999	-0.34	58	58
FRAP1	0.016	0.15	-9999	-0.39	58	58
FOXO3	0.037	0.098	-9999	-0.36	16	16
AKT1	0.032	0.1	-9999	-0.39	16	16
GAB2	0.006	0.042	-9999	-0.42	5	5
SMPD1	0.017	0.019	-9999	-10000	0	0
SGMS1	0.017	0.019	-9999	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
mol:GDP	0.013	0.026	-9999	-0.24	5	5
CALM1	0.011	0	-9999	-10000	0	0
cell proliferation	0.019	0.074	-9999	-0.29	20	20
EIF3A	0.011	0	-9999	-10000	0	0
PI3K	0.016	0.031	-9999	-0.29	5	5
RPS6KB1	0.013	0.02	-9999	-10000	0	0
mol:sphingomyelin	0	0.001	-9999	-10000	0	0
natural killer cell activation	0	0.003	-9999	-0.012	10	10
JAK3	0.01	0.022	-9999	-0.27	3	3
PIK3R1	0.008	0.038	-9999	-0.42	4	4
JAK1	0.01	0.033	-9999	-0.42	3	3
NFKB1	0.01	0.019	-9999	-0.42	1	1
MYC	0.027	0.15	-9999	-0.87	11	11
MYB	0.017	0.038	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.038	0.07	-9999	-0.3	7	7
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.024	0.019	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.038	0.069	-9999	-0.29	7	7
Rac1/GDP	0.018	0.024	-9999	-0.21	5	5
T cell proliferation	0.041	0.067	-9999	-0.34	3	3
SHC1	0.01	0.004	-9999	-10000	0	0
RAC1	0.011	0	-9999	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.002	0.006	-9999	-10000	0	0
PRKCZ	0.041	0.068	-9999	-0.35	3	3
NF kappa B1 p50/RelA	-0.03	0.11	-9999	-0.34	58	58
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.034	0.043	-9999	-0.42	2	2
HSP90AA1	0.011	0	-9999	-10000	0	0
RELA	0.011	0	-9999	-10000	0	0
IL2RA	0	0.053	-9999	-0.28	17	17
IL2RB	0.011	0.019	-9999	-0.42	1	1
TERT	-0.11	0.14	-9999	-0.27	225	225
E2F1	0.019	0.028	-9999	-10000	0	0
SOS1	0.01	0.004	-9999	-10000	0	0
RPS6	0.011	0	-9999	-10000	0	0
mol:cAMP	-0.001	0.003	-9999	-10000	0	0
PTPN11	0.01	0.004	-9999	-10000	0	0
IL2RG	0.007	0.039	-9999	-0.31	7	7
actin cytoskeleton organization	0.041	0.067	-9999	-0.34	3	3
GRB2	0.01	0.004	-9999	-10000	0	0
IL2	-0.004	0.05	-9999	-0.27	17	17
PIK3CA	0.011	0.019	-9999	-0.42	1	1
Rac1/GTP	0.024	0.024	-9999	-0.2	5	5
LCK	0.009	0.031	-9999	-0.3	5	5
BCL2	-0.021	0.26	-9999	-0.82	48	48

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.015	0.084	-9999	-0.38	21	21
PDGFB-D/PDGFRB/SLAP	0.004	0.06	-9999	-0.28	21	21
PDGFB-D/PDGFRB/APS/CBL	0.012	0.05	-9999	-0.23	21	21
AKT1	0.033	0.047	-9999	-0.3	2	2
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.015	0.09	-9999	-0.41	21	21
PIK3CA	0.01	0.019	-9999	-0.42	1	1
FGR	-0.024	0.1	-9999	-0.39	31	31
mol:Ca2+	0.01	0.095	-9999	-0.44	21	21
MYC	0.019	0.13	-9999	-0.67	13	13
SHC1	0.011	0	-9999	-10000	0	0
HRAS/GDP	0.019	0.046	-9999	-0.18	26	26
LRP1/PDGFRB/PDGFB	0.011	0.054	-9999	-0.24	22	22
GRB10	0.01	0.019	-9999	-0.42	1	1
PTPN11	0.011	0	-9999	-10000	0	0
GO:0007205	0.01	0.096	-9999	-0.45	21	21
PTEN	0.006	0.046	-9999	-0.42	6	6
GRB2	0.011	0	-9999	-10000	0	0
GRB7	-0.007	0.07	-9999	-0.28	31	31
PDGFB-D/PDGFRB/SHP2	0.004	0.06	-9999	-0.28	21	21
PDGFB-D/PDGFRB/GRB10	0.003	0.061	-9999	-0.28	22	22
cell cycle arrest	0.004	0.06	-9999	-0.28	21	21
HRAS	0.011	0	-9999	-10000	0	0
HIF1A	0.037	0.043	-9999	-0.27	2	2
GAB1	0.013	0.093	-9999	-0.41	21	21
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.017	0.085	-9999	-0.37	21	21
PDGFB-D/PDGFRB	0.012	0.052	-9999	-0.24	21	21
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.004	0.06	-9999	-0.28	21	21
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.015	0.071	-9999	-0.34	21	21
positive regulation of MAPKKK cascade	0.004	0.06	-9999	-0.28	21	21
PIK3R1	0.007	0.038	-9999	-0.42	4	4
mol:IP3	0.01	0.097	-9999	-0.45	21	21
E5	0	0.001	-9999	-10000	0	0
CSK	0.01	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.008	0.078	-9999	-0.24	49	49
SHB	0.011	0	-9999	-10000	0	0
BLK	-0.009	0.054	-9999	-0.26	21	21
PTPN2	0.011	0.002	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.004	0.06	-9999	-0.28	21	21
BCAR1	0.011	0	-9999	-10000	0	0
VAV2	0.016	0.096	-9999	-0.4	21	21
CBL	0.011	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.003	0.061	-9999	-0.28	23	23
LCK	-0.012	0.066	-9999	-0.29	21	21
PDGFRB	-0.006	0.086	-9999	-0.42	21	21
ACP1	0.011	0	-9999	-10000	0	0
HCK	-0.011	0.053	-9999	-0.26	21	21
ABL1	0.014	0.079	-9999	-0.35	21	21
PDGFB-D/PDGFRB/CBL	0.011	0.1	-9999	-0.47	21	21
PTPN1	0.011	0.002	-9999	-10000	0	0
SNX15	0.011	0	-9999	-10000	0	0
STAT3	0.011	0	-9999	-10000	0	0
STAT1	0.01	0.012	-9999	-0.27	1	1
cell proliferation	0.021	0.12	-9999	-0.6	13	13
SLA	0.011	0	-9999	-10000	0	0
actin cytoskeleton reorganization	0.03	0.042	-9999	-10000	0	0
SRC	-0.011	0.053	-9999	-0.26	21	21
PI3K	-0.01	0.04	-9999	-0.34	2	2
PDGFB-D/PDGFRB/GRB7/SHC	0.002	0.065	-9999	-0.25	23	23
SH2B2	0.011	0	-9999	-10000	0	0
PLCgamma1/SPHK1	0.015	0.092	-9999	-0.42	21	21
LYN	-0.011	0.052	-9999	-0.26	21	21
LRP1	0.009	0.027	-9999	-0.42	2	2
SOS1	0.011	0	-9999	-10000	0	0
STAT5B	0.01	0.019	-9999	-0.42	1	1
STAT5A	0.011	0	-9999	-10000	0	0
NCK1-2/p130 Cas	-0.004	0.038	-9999	-10000	0	0
SPHK1	0.01	0.018	-9999	-0.27	2	2
EDG1	0.001	0.002	-9999	-10000	0	0
mol:DAG	0.01	0.097	-9999	-0.45	21	21
PLCG1	0.009	0.099	-9999	-0.46	21	21
NHERF/PDGFRB	0.01	0.052	-9999	-0.23	21	21
YES1	-0.011	0.052	-9999	-0.26	21	21
cell migration	0.01	0.052	-9999	-0.23	21	21
SHC/Grb2/SOS1	-0.003	0.037	-9999	-0.18	1	1
SLC9A3R2	0.011	0	-9999	-10000	0	0
SLC9A3R1	0.008	0.028	-9999	-0.27	5	5
NHERF1-2/PDGFRB/PTEN	0.014	0.055	-9999	-0.21	26	26
FYN	-0.011	0.052	-9999	-0.26	21	21
DOK1	0.016	0.046	-9999	-0.21	21	21
HRAS/GTP	0.008	0	-9999	-10000	0	0
PDGFB	0.011	0	-9999	-10000	0	0
RAC1	0.021	0.1	-9999	-0.37	31	31
PRKCD	0.017	0.046	-9999	-0.21	21	21
FER	0.017	0.046	-9999	-0.21	21	21
MAPKKK cascade	-0.006	0.035	-9999	-0.18	1	1
RASA1	0.014	0.051	-9999	-0.21	26	26
NCK1	0.009	0.027	-9999	-0.42	2	2
NCK2	0.011	0	-9999	-10000	0	0
p62DOK/Csk	0.021	0.042	-9999	-0.18	21	21
PDGFB-D/PDGFRB/SHB	0.004	0.06	-9999	-0.28	21	21
chemotaxis	0.015	0.077	-9999	-0.34	21	21
STAT1-3-5/STAT1-3-5	-0.007	0.033	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	-0.004	0.06	-9999	-0.3	21	21
PTPRJ	0.01	0.018	-9999	-0.27	2	2

×

IL12-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
IL12/IL12R/TYK2/JAK2/SOCS1	0.024	0.07	-10000	0	-0.32	8	8
TBX21	0.016	0.2	-10000	0	-0.88	11	11
B2M	0.011	0.005	-10000	0	-10000	0	0
TYK2	0.014	0.015	-10000	0	-10000	0	0
IL12RB1	0.005	0.06	-10000	0	-0.35	13	13
GADD45B	0.041	0.16	-10000	0	-0.73	8	8
IL12RB2	0.001	0.062	-10000	0	-0.28	23	23
GADD45G	0.02	0.24	-10000	0	-1	19	19
natural killer cell activation	0.003	0.015	-10000	0	-10000	0	0
RELB	0.011	0	-10000	0	-10000	0	0
RELA	0.011	0	-10000	0	-10000	0	0
IL18	0.011	0.033	-10000	0	-0.27	7	7
IL2RA	0.001	0.053	-10000	0	-0.28	17	17
IFNG	-0.009	0.067	-10000	0	-0.27	31	31
STAT3 (dimer)	0.032	0.17	-10000	0	-0.6	14	14
HLA-DRB5	-0.005	0.063	-10000	0	-0.37	14	14
FASLG	0.015	0.2	-10000	0	-0.99	9	9
NF kappa B2 p52/RelB	-0.058	0.14	-10000	0	-0.63	20	20
CD4	0.005	0.016	-10000	0	-0.29	1	1
SOCS1	0.009	0.023	-10000	0	-0.34	2	2
EntrezGene:6955	-0.007	0.014	-10000	0	-10000	0	0
CD3D	-0.008	0.069	-10000	0	-0.33	21	21
CD3E	0	0.056	-10000	0	-0.37	11	11
CD3G	0.001	0.042	-10000	0	-0.36	6	6
IL12Rbeta2/JAK2	0.009	0.063	-10000	0	-0.22	26	26
CCL3	0.018	0.19	-10000	0	-0.94	7	7
CCL4	0.016	0.2	-10000	0	-0.91	11	11
HLA-A	0.011	0.013	-10000	0	-0.27	1	1
IL18/IL18R	0.043	0.048	-10000	0	-0.25	8	8
NOS2	0.022	0.2	-10000	0	-1	9	9
IL12/IL12R/TYK2/JAK2/SPHK2	0.025	0.067	-10000	0	-0.28	9	9
IL1R1	0.009	0.23	-10000	0	-1.1	14	14
IL4	0.001	0.016	-10000	0	-10000	0	0
JAK2	0.006	0.059	-10000	0	-0.42	9	9
EntrezGene:6957	-0.006	0.012	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.001	0.12	-10000	0	-0.64	12	12
RAB7A	0.046	0.17	-10000	0	-0.63	13	13
lysosomal transport	0.046	0.16	-10000	0	-0.6	13	13
FOS	-0.34	0.58	-10000	0	-1.1	175	175
STAT4 (dimer)	0.042	0.18	-10000	0	-0.62	16	16
STAT5A (dimer)	-0.06	0.15	-10000	0	-0.62	22	22
GZMA	0.002	0.24	-10000	0	-0.98	19	19
GZMB	0.009	0.2	-10000	0	-1.1	8	8
HLX	0.011	0	-10000	0	-10000	0	0
LCK	0.026	0.2	-10000	0	-0.67	22	22
TCR/CD3/MHC II/CD4	-0.049	0.13	-10000	0	-0.35	27	27
IL2/IL2R	0.011	0.049	-10000	0	-0.26	10	10
MAPK14	0.038	0.19	-10000	0	-0.69	19	19
CCR5	0.034	0.18	-10000	0	-0.92	9	9
IL1B	0.01	0.043	-10000	0	-0.44	4	4
STAT6	0.025	0.071	-10000	0	-0.3	5	5
STAT4	0.01	0.019	-10000	0	-0.42	1	1
STAT3	0.011	0	-10000	0	-10000	0	0
STAT1	0.01	0.012	-10000	0	-0.27	1	1
NFKB1	0.01	0.019	-10000	0	-0.42	1	1
NFKB2	0.011	0	-10000	0	-10000	0	0
IL12B	0.01	0.019	-10000	0	-0.26	1	1
CD8A	0.003	0.059	-10000	0	-0.37	12	12
CD8B	-0.007	0.075	-10000	0	-0.3	31	31
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.024	0.07	0.32	8	-10000	0	8
IL2RB	0.01	0.019	-10000	0	-0.42	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.044	0.17	-10000	0	-0.58	16	16
IL2RG	0.006	0.038	-10000	0	-0.31	7	7
IL12	0.013	0.046	-10000	0	-0.26	7	7
STAT5A	0.011	0	-10000	0	-10000	0	0
CD247	0.006	0.024	-10000	0	-0.35	2	2
IL2	-0.005	0.05	-10000	0	-0.27	17	17
SPHK2	0.011	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.004	0.057	-10000	0	-0.31	15	15
IL12/IL12R/TYK2/JAK2	0.028	0.21	-10000	0	-0.72	21	21
MAP2K3	0.033	0.19	-10000	0	-0.67	20	20
RIPK2	0.011	0	-10000	0	-10000	0	0
MAP2K6	0.036	0.19	-10000	0	-0.68	19	19
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.002	0.034	-10000	0	-0.43	3	3
IL18RAP	0.01	0.04	-10000	0	-0.35	6	6
IL12Rbeta1/TYK2	0.014	0.047	-10000	0	-0.24	13	13
EOMES	-0.008	0.13	-10000	0	-1.2	6	6
STAT1 (dimer)	0.036	0.16	-10000	0	-0.64	11	11
T cell proliferation	0.04	0.15	-10000	0	-0.5	17	17
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.011	0.039	-10000	0	-0.42	4	4
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.032	0.12	0.26	1	-0.55	17	18
ATF2	0.042	0.18	-10000	0	-0.64	19	19

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.009	0.045	-9999	-10000	0	0
epithelial cell differentiation	-0.042	0.078	-9999	-0.32	14	14
ITCH	0.016	0.01	-9999	-10000	0	0
WWP1	0.008	0.04	-9999	-10000	0	0
FYN	0.011	0	-9999	-10000	0	0
EGFR	-0.001	0.068	-9999	-0.41	14	14
PRL	-0.012	0.089	-9999	-0.41	24	24
neuron projection morphogenesis	0.03	0.046	-9999	-10000	0	0
PTPRZ1	-0.01	0.064	-9999	-0.27	29	29
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.023	0.049	-9999	-0.27	1	1
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	0.007	0.055	-9999	-0.3	5	5
ADAM17	0.016	0.01	-9999	-10000	0	0
ErbB4/ErbB4	0.005	0.051	-9999	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.003	0.051	-9999	-0.28	1	1
NCOR1	0.011	0	-9999	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	0.012	0.051	-9999	-0.28	5	5
GRIN2B	0.01	0.056	-9999	-0.29	6	6
ErbB4/ErbB2/betacellulin	0.008	0.055	-9999	-0.29	3	3
STAT1	0.01	0.012	-9999	-0.27	1	1
HBEGF	0.01	0.019	-9999	-0.42	1	1
PRLR	-0.073	0.17	-9999	-0.42	101	101
E4ICDs/ETO2	-0.02	0.092	-9999	-0.35	10	10
axon guidance	0.013	0.034	-9999	-10000	0	0
NEDD4	-0.023	0.12	-9999	-0.42	44	44
Prolactin receptor/Prolactin receptor/Prolactin	-0.059	0.14	-9999	-0.3	118	118
CBFA2T3	-0.041	0.14	-9999	-0.42	62	62
ErbB4/ErbB2/HBEGF	0.015	0.039	-9999	-10000	0	0
MAPK3	0.026	0.047	-9999	-10000	0	0
STAT1 (dimer)	0.009	0.044	-9999	-10000	0	0
MAPK1	0.026	0.047	-9999	-10000	0	0
JAK2	0.003	0.056	-9999	-0.42	9	9
ErbB4/ErbB2/neuregulin 1 beta	0.009	0.056	-9999	-0.28	6	6
NRG1	0.011	0.053	-9999	-0.28	16	16
NRG3	-0.004	0.053	-9999	-0.27	19	19
NRG2	-0.036	0.13	-9999	-0.41	56	56
NRG4	-0.013	0.078	-9999	-0.27	43	43
heart development	0.013	0.034	-9999	-10000	0	0
neural crest cell migration	0.009	0.056	-9999	-0.28	6	6
ERBB2	0.015	0.032	-9999	-0.18	13	13
WWOX/E4ICDs	0.009	0.043	-9999	-10000	0	0
SHC1	0.011	0	-9999	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.002	0.07	-9999	-0.34	7	7
apoptosis	0	0.038	-9999	-10000	0	0
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.017	0.088	-9999	-0.35	9	9
ErbB4/ErbB2/epiregulin	0.009	0.056	-9999	-10000	0	0
ErbB4/ErbB4/betacellulin/betacellulin	0	0.062	-9999	-0.36	3	3
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.028	0.11	-9999	-0.33	33	33
MDM2	0.01	0.044	-9999	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	0.012	0.047	-9999	-0.26	5	5
STAT5A	0.018	0.032	-9999	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	0.007	0.066	-9999	-0.33	9	9
DLG4	0.009	0.027	-9999	-0.42	2	2
GRB2/SHC	0.016	0	-9999	-10000	0	0
E4ICDs/TAB2/NCoR1	0.008	0.039	-9999	-10000	0	0
STAT5A (dimer)	-0.044	0.083	-9999	-0.35	10	10
MAP3K7IP2	0	0	-9999	-10000	0	0
STAT5B (dimer)	0.017	0.035	-9999	-0.33	1	1
LRIG1	0.008	0.033	-9999	-0.42	3	3
EREG	-0.024	0.091	-9999	-0.27	61	61
BTC	-0.005	0.079	-9999	-0.42	18	18
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.015	0.032	-9999	-10000	0	0
ERBB4	0.005	0.051	-9999	-10000	0	0
STAT5B	0.01	0.019	-9999	-0.42	1	1
YAP1	0	0.025	-9999	-0.52	1	1
GRB2	0.011	0	-9999	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0.008	0.055	-9999	-10000	0	0
glial cell differentiation	0.006	0.034	-9999	-10000	0	0
WWOX	0.011	0	-9999	-10000	0	0
cell proliferation	0.01	0.066	-9999	-10000	0	0

×

Class IB PI3K non-lipid kinase events

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
cAMP biosynthetic process	-0.003	0.049	0.32	11	-10000	0	11
PI3K Class IB/PDE3B	0.003	0.05	-10000	0	-0.32	11	11
PDE3B	0.003	0.05	-10000	0	-0.32	11	11

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.015	0.002	-9999	-10000	0	0
RAS family/GTP	0.008	0.048	-9999	-0.23	12	12
NFATC4	0.015	0.042	-9999	-0.25	2	2
ERBB2IP	0.011	0.001	-9999	-10000	0	0
HSP90 (dimer)	0.011	0	-9999	-10000	0	0
mammary gland morphogenesis	0.004	0.045	-9999	-0.21	17	17
JUN	-0.005	0.07	-9999	-0.35	4	4
HRAS	0.01	0.001	-9999	-10000	0	0
DOCK7	0.014	0.045	-9999	-0.31	2	2
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.004	0.048	-9999	-0.22	17	17
AKT1	0.009	0.001	-9999	-10000	0	0
BAD	0.015	0.001	-9999	-10000	0	0
MAPK10	-0.012	0.067	-9999	-0.15	47	47
mol:GTP	-0.001	0.001	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	0.004	0.048	-9999	-0.22	17	17
RAF1	0.01	0.054	-9999	-0.23	12	12
ErbB2/ErbB3/neuregulin 2	-0.019	0.076	-9999	-0.22	57	57
STAT3	0.001	0.003	-9999	-10000	0	0
cell migration	-0.001	0.061	-9999	-0.2	14	14
mol:PI-3-4-5-P3	0	0.001	-9999	-10000	0	0
cell proliferation	-0.079	0.19	-9999	-0.52	17	17
FOS	-0.13	0.25	-9999	-0.47	174	174
NRAS	0.01	0.001	-9999	-10000	0	0
mol:Ca2+	0.004	0.045	-9999	-0.21	17	17
MAPK3	-0.041	0.13	-9999	-0.41	16	16
MAPK1	-0.041	0.13	-9999	-0.41	16	16
JAK2	0.011	0.05	-9999	-0.2	12	12
NF2	0	0.002	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0.011	0.049	-9999	-0.24	17	17
NRG1	-0.003	0.073	-9999	-0.41	16	16
GRB2/SOS1	0.015	0.001	-9999	-10000	0	0
MAPK8	0.013	0.056	-9999	-0.23	22	22
MAPK9	0.021	0.027	-9999	-0.16	2	2
ERBB2	-0.005	0.03	-9999	-0.19	13	13
ERBB3	0.007	0.033	-9999	-0.42	3	3
SHC1	0.01	0.001	-9999	-10000	0	0
RAC1	0.011	0	-9999	-10000	0	0
apoptosis	0.001	0.006	-9999	-10000	0	0
STAT3 (dimer)	0.016	0.003	-9999	-10000	0	0
RNF41	0.019	0.003	-9999	-10000	0	0
FRAP1	0.007	0.001	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.006	0.027	-9999	-0.23	2	2
ErbB2/ErbB2/HSP90 (dimer)	-0.004	0.023	-9999	-0.15	1	1
CHRNA1	-0.048	0.12	-9999	-0.38	8	8
myelination	0.02	0.04	-9999	-0.24	2	2
PPP3CB	0.014	0.043	-9999	-0.19	12	12
KRAS	0.01	0.012	-9999	-0.27	1	1
RAC1-CDC42/GDP	0.022	0.043	-9999	-0.2	17	17
NRG2	-0.036	0.13	-9999	-0.41	56	56
mol:GDP	0.011	0.049	-9999	-0.24	17	17
SOS1	0.01	0.001	-9999	-10000	0	0
MAP2K2	0.003	0.062	-9999	-0.3	5	5
SRC	0.011	0	-9999	-10000	0	0
mol:cAMP	0	0.001	-9999	-10000	0	0
PTPN11	0.014	0.045	-9999	-0.31	2	2
MAP2K1	-0.049	0.13	-9999	-0.43	16	16
heart morphogenesis	0.004	0.045	-9999	-0.21	17	17
RAS family/GDP	0.017	0.046	-9999	-0.26	5	5
GRB2	0.01	0.001	-9999	-10000	0	0
PRKACA	-0.001	0.003	-9999	-10000	0	0
CHRNE	0.006	0.023	-9999	-0.19	4	4
HSP90AA1	0.011	0	-9999	-10000	0	0
activation of caspase activity	-0.009	0.001	-9999	-10000	0	0
nervous system development	0.004	0.045	-9999	-0.21	17	17
CDC42	0.011	0	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class III

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
EP300	0.011	0	-10000	0	-10000	0	0
HDAC4	0.011	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.012	0.03	0.2	9	-10000	0	9
CDKN1A	-0.003	0.048	-10000	0	-0.62	3	3
KAT2B	0.002	0.059	-10000	0	-0.42	10	10
BAX	0.011	0	-10000	0	-10000	0	0
FOXO3	0	0.006	-10000	0	-10000	0	0
FOXO1	0.008	0.033	-10000	0	-0.42	3	3
FOXO4	0.016	0.02	-10000	0	-0.24	3	3
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.011	0	-10000	0	-10000	0	0
TAT	0.006	0.018	-10000	0	-0.27	2	2
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.011	0.068	-10000	0	-0.2	56	56
PPARGC1A	-0.081	0.18	-10000	0	-0.42	110	110
FHL2	0.002	0.059	-10000	0	-0.42	10	10
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0	0.021	0.14	3	-0.29	2	5
HIST2H4A	0.012	0.03	-10000	0	-0.2	9	9
SIRT1/FOXO3a	0	0.018	0.13	3	-0.23	2	5
SIRT1	0.006	0.03	0.18	3	-0.42	2	5
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0	0.018	0.13	3	-0.23	2	5
SIRT1/Histone H1b	0.014	0.023	0.14	2	-0.23	3	5
apoptosis	0	0.018	0.23	2	-0.13	3	5
SIRT1/PGC1A	-0.051	0.1	0.12	3	-0.24	111	114
p53/SIRT1	0	0.035	0.36	3	-0.29	3	6
SIRT1/FOXO4	0.016	0.024	0.14	3	-0.21	5	8
FOXO1/FHL2/SIRT1	0.012	0.039	-10000	0	-0.21	15	15
HIST1H1E	0.014	0.017	-10000	0	-0.24	1	1
SIRT1/p300	0	0.021	0.14	3	-0.29	2	5
muscle cell differentiation	0.011	0.058	0.27	11	-0.13	2	13
TP53	0.007	0.023	0.18	3	-0.42	1	4
KU70/SIRT1/BAX	0	0.018	0.13	3	-0.23	2	5
CREBBP	0.01	0.019	-10000	0	-0.42	1	1
MEF2D	0.011	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.001	0.024	0.14	3	-0.23	4	7
ACSS2	0.015	0.021	-10000	0	-0.29	2	2
SIRT1/PCAF/MYOD	-0.011	0.058	0.14	2	-0.27	11	13

×

Signaling mediated by p38-gamma and p38-delta

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.02	0.017	-9999	-10000	0	0
SNTA1	0.011	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.02	0.017	-9999	-10000	0	0
MAPK12	-0.007	0.066	-9999	-0.21	27	27
CCND1	0.004	0.03	-9999	-10000	0	0
p38 gamma/SNTA1	-0.001	0.062	-9999	-0.19	27	27
MAP2K3	0.011	0	-9999	-10000	0	0
PKN1	0.011	0	-9999	-10000	0	0
G2/M transition checkpoint	-0.007	0.066	-9999	-0.21	27	27
MAP2K6	-0.014	0.073	-9999	-0.24	26	26
MAPT	0.001	0.062	-9999	-0.28	20	20
MAPK13	0.015	0.021	-9999	-0.18	6	6
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	-0.002	0.064	-9999	-0.28	26	26

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.011	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.015	0.083	-9999	-0.22	1	1
Syndecan-3/Neurocan	0.007	0.022	-9999	-10000	0	0
POMC	-0.008	0.078	-9999	-0.33	27	27
EGFR	-0.001	0.068	-9999	-0.41	14	14
Syndecan-3/EGFR	0.014	0.033	-9999	-0.19	13	13
AGRP	0.006	0.013	-9999	-0.27	1	1
NCSTN	0.011	0	-9999	-10000	0	0
PSENEN	0.011	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.007	0.038	-9999	-0.42	4	4
APH1A	0.011	0	-9999	-10000	0	0
NCAN	-0.002	0.047	-9999	-0.27	15	15
long-term memory	0.025	0.005	-9999	-10000	0	0
Syndecan-3/IL8	-0.005	0.05	-9999	-10000	0	0
PSEN1	0.011	0	-9999	-10000	0	0
Src/Cortactin	0.016	0	-9999	-10000	0	0
FYN	0.011	0	-9999	-10000	0	0
limb bud formation	0	0.004	-9999	-10000	0	0
MC4R	0.001	0.035	-9999	-0.27	8	8
SRC	0.011	0	-9999	-10000	0	0
PTN	-0.088	0.18	-9999	-0.42	119	119
FGFR/FGF/Syndecan-3	0	0.004	-9999	-10000	0	0
neuron projection morphogenesis	-0.025	0.077	-9999	-0.27	2	2
Syndecan-3/AgRP	0.011	0.012	-9999	-10000	0	0
Syndecan-3/AgRP/MC4R	0.006	0.02	-9999	-10000	0	0
Fyn/Cortactin	0.016	0	-9999	-10000	0	0
SDC3	0	0.004	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.005	0.05	-9999	-10000	0	0
IL8	-0.045	0.11	-9999	-0.27	101	101
Syndecan-3/Fyn/Cortactin	0.026	0.005	-9999	-10000	0	0
Syndecan-3/CASK	0	0.004	-9999	-10000	0	0
alpha-MSH/MC4R	-0.003	0.058	-9999	-0.21	35	35
Gamma Secretase	0.03	0.019	-9999	-0.18	4	4

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	0.021	0.038	-9999	-0.2	14	14
HDAC3	0.011	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC4	0.012	0.004	-9999	-10000	0	0
GATA1/HDAC5	0.012	0.004	-9999	-10000	0	0
GATA2/HDAC5	-0.012	0.088	-9999	-0.29	48	48
HDAC5/BCL6/BCoR	0.021	0.011	-9999	-0.23	1	1
HDAC9	0.001	0.062	-9999	-0.42	11	11
Glucocorticoid receptor/Hsp90/HDAC6	-0.025	0.098	-9999	-0.23	94	94
HDAC4/ANKRA2	0.015	0.013	-9999	-0.29	1	1
HDAC5/YWHAB	0.016	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.017	0	-9999	-10000	0	0
GATA2	-0.029	0.12	-9999	-0.42	48	48
HDAC4/RFXANK	0.015	0.015	-9999	-0.18	3	3
BCOR	0.011	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.011	0	-9999	-10000	0	0
HDAC5	0.011	0	-9999	-10000	0	0
GNB1/GNG2	0.007	0.05	-9999	-0.28	15	15
Histones	0.027	0.029	-9999	-10000	0	0
ADRBK1	0.011	0	-9999	-10000	0	0
HDAC4	0.011	0	-9999	-10000	0	0
XPO1	0.011	0	-9999	-10000	0	0
HDAC5/ANKRA2	0.015	0.013	-9999	-0.29	1	1
HDAC4/Ubc9	0.016	0	-9999	-10000	0	0
HDAC7	0.011	0	-9999	-10000	0	0
HDAC5/14-3-3 E	0.016	0	-9999	-10000	0	0
TUBA1B	0.011	0	-9999	-10000	0	0
HDAC6	0.011	0	-9999	-10000	0	0
HDAC5/RFXANK	0.015	0.015	-9999	-0.18	3	3
CAMK4	0.006	0.038	-9999	-0.31	7	7
Tubulin/HDAC6	0.019	0.024	-9999	-0.23	3	3
SUMO1	0.011	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.011	0	-9999	-10000	0	0
GATA1	0.006	0.005	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.011	0	-9999	-10000	0	0
NR3C1	-0.068	0.16	-9999	-0.42	94	94
SUMO1/HDAC4	0.024	0	-9999	-10000	0	0
SRF	0.011	0	-9999	-10000	0	0
HDAC4/YWHAB	0.016	0	-9999	-10000	0	0
Tubulin	0.013	0.028	-9999	-0.22	7	7
HDAC4/14-3-3 E	0.016	0	-9999	-10000	0	0
GNB1	0.011	0	-9999	-10000	0	0
RANGAP1	0.011	0	-9999	-10000	0	0
BCL6/BCoR	0.015	0.013	-9999	-0.29	1	1
HDAC4/HDAC3/SMRT (N-CoR2)	0.022	0	-9999	-10000	0	0
HDAC4/SRF	0.019	0.022	-9999	-0.23	2	2
HDAC4/ER alpha	-0.017	0.094	-9999	-0.29	56	56
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.027	0.028	-9999	-10000	0	0
cell motility	0.019	0.024	-9999	-0.23	3	3
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.011	0	-9999	-10000	0	0
HDAC7/HDAC3	0.016	0	-9999	-10000	0	0
BCL6	0.01	0.019	-9999	-0.42	1	1
HDAC4/CaMK II delta B	0.011	0	-9999	-10000	0	0
Hsp90/HDAC6	0.016	0	-9999	-10000	0	0
ESR1	-0.036	0.13	-9999	-0.42	56	56
HDAC6/HDAC11	0.015	0.008	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.026	0	-9999	-10000	0	0
NPC	0.006	0	-9999	-10000	0	0
MEF2C	-0.039	0.14	-9999	-0.42	60	60
RAN	0.011	0	-9999	-10000	0	0
HDAC4/MEF2C	0.006	0.07	-9999	-0.18	60	60
GNG2	-0.002	0.071	-9999	-0.41	15	15
NCOR2	0.011	0	-9999	-10000	0	0
TUBB2A	0.006	0.041	-9999	-0.33	7	7
HDAC11	0.01	0.012	-9999	-0.27	1	1
HSP90AA1	0.011	0	-9999	-10000	0	0
RANBP2	0.011	0	-9999	-10000	0	0
ANKRA2	0.01	0.019	-9999	-0.42	1	1
RFXANK	0.009	0.022	-9999	-0.27	3	3
nuclear import	-0.023	0	-9999	-10000	0	0

×

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
SPHK2	0.016	0.019	-10000	0	-0.29	2	2
MAP4K4	0.03	0.032	-10000	0	-0.4	1	1
BAG4	0.008	0.033	-10000	0	-0.42	3	3
PKC zeta/ceramide	-0.001	0.015	0.12	2	-0.17	2	4
NFKBIA	0.011	0	-10000	0	-10000	0	0
BIRC3	0.003	0.057	-10000	0	-0.4	10	10
BAX	0.002	0.006	-10000	0	-10000	0	0
RIPK1	0.011	0	-10000	0	-10000	0	0
AKT1	0.014	0.002	-10000	0	-10000	0	0
BAD	-0.001	0.011	0.13	2	-10000	0	2
SMPD1	0.017	0.02	-10000	0	-0.17	2	2
RB1	-0.002	0.02	0.13	2	-0.22	3	5
FADD/Caspase 8	0.037	0.031	-10000	0	-0.39	1	1
MAP2K4	0.004	0.014	0.13	2	-0.2	1	3
NSMAF	0.011	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.004	0.014	0.13	2	-0.2	1	3
EGF	-0.002	0.058	-10000	0	-0.29	20	20
mol:ceramide	-0.008	0.012	0.14	2	-10000	0	2
MADD	0.011	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.016	0.019	-10000	0	-0.29	2	2
ASAH1	0.011	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.003	0.02	0.13	2	-0.22	3	5
cell proliferation	-0.014	0.072	-10000	0	-0.16	101	101
BID	0.025	0.024	-10000	0	-0.29	1	1
MAP3K1	-0.001	0.011	0.13	2	-10000	0	2
EIF2A	0.009	0.01	0.14	1	-10000	0	1
TRADD	0.011	0	-10000	0	-10000	0	0
CRADD	0.011	0	-10000	0	-10000	0	0
MAPK3	0.012	0.013	0.13	2	-0.18	1	3
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.012	0.013	0.13	2	-0.18	1	3
Cathepsin D/ceramide	0	0.012	0.12	2	-0.13	1	3
FADD	0.03	0.032	-10000	0	-0.4	1	1
KSR1	-0.002	0.014	0.13	2	-0.21	1	3
MAPK8	0.005	0.026	0.14	1	-0.21	6	7
PRKRA	-0.001	0.011	0.13	2	-10000	0	2
PDGFA	0.009	0.027	-10000	0	-0.42	2	2
TRAF2	0.011	0	-10000	0	-10000	0	0
IGF1	-0.074	0.17	-10000	0	-0.42	102	102
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.008	0.012	0.14	2	-10000	0	2
CTSD	0.01	0.012	-10000	0	-0.27	1	1
regulation of nitric oxide biosynthetic process	0.015	0.013	-10000	0	-0.28	1	1
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.014	0.076	-10000	0	-0.17	101	101
PRKCD	0.011	0	-10000	0	-10000	0	0
PRKCZ	0.009	0.023	-10000	0	-0.34	2	2
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.016	0.019	-10000	0	-0.29	2	2
RelA/NF kappa B1	0.015	0.013	-10000	0	-0.29	1	1
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.011	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.025	0.034	-10000	0	-0.43	1	1
TNFR1A/BAG4/TNF-alpha	0.004	0.052	-10000	0	-0.23	5	5
mol:Sphingosine-1-phosphate	0.016	0.019	-10000	0	-0.28	2	2
MAP2K1	0.009	0.013	0.13	2	-0.18	1	3
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.011	0	-10000	0	-10000	0	0
CYCS	0.014	0.04	0.14	49	-10000	0	49
TNFRSF1A	0.011	0	-10000	0	-10000	0	0
NFKB1	0.01	0.019	-10000	0	-0.42	1	1
TNFR1A/BAG4	0.014	0.023	-10000	0	-0.29	3	3
EIF2AK2	0.004	0.01	0.13	2	-10000	0	2
TNF-alpha/TNFR1A/FAN	0.006	0.048	-10000	0	-0.23	2	2
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.03	0.022	-10000	0	-0.23	1	1
MAP2K2	0.009	0.013	0.14	1	-0.18	1	2
SMPD3	0.019	0.029	-10000	0	-0.25	4	4
TNF	-0.018	0.086	-10000	0	-0.28	50	50
PKC zeta/PAR4	0.015	0.016	-10000	0	-0.23	2	2
mol:PHOSPHOCHOLINE	-0.004	0.018	0.16	3	-10000	0	3
NF kappa B1/RelA/I kappa B alpha	0.031	0.015	-10000	0	-0.18	2	2
AIFM1	0.014	0.04	0.14	49	-10000	0	49
BCL2	-0.029	0.12	-10000	0	-0.42	48	48

×

HIF-2-alpha transcription factor network

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
MMP14	-0.006	0.049	-10000	0	-1.1	1	1
oxygen homeostasis	-0.002	0.014	-10000	0	-10000	0	0
TCEB2	0.011	0	-10000	0	-10000	0	0
TCEB1	0.011	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.017	0.04	-10000	0	-0.29	5	5
EPO	-0.006	0.18	-10000	0	-0.51	12	12
FIH (dimer)	0.009	0.013	-10000	0	-10000	0	0
APEX1	0.008	0.014	-10000	0	-10000	0	0
SERPINE1	-0.007	0.19	-10000	0	-0.59	12	12
FLT1	-0.016	0.095	-10000	0	-0.99	4	4
ADORA2A	-0.005	0.18	-10000	0	-0.52	10	10
germ cell development	-0.013	0.2	-10000	0	-0.53	23	23
SLC11A2	-0.005	0.19	-10000	0	-0.52	12	12
BHLHE40	-0.005	0.19	-10000	0	-0.52	12	12
HIF1AN	0.009	0.013	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	0.001	0.11	-10000	0	-0.4	5	5
ETS1	0.019	0.035	-10000	0	-0.43	3	3
CITED2	-0.035	0.18	-10000	0	-1	16	16
KDR	-0.062	0.26	-10000	0	-1.1	29	29
PGK1	-0.005	0.19	-10000	0	-0.52	12	12
SIRT1	0.009	0.027	-10000	0	-0.42	2	2
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	-0.008	0.21	-10000	0	-0.58	13	13
EPAS1	0.013	0.086	-10000	0	-0.36	4	4
SP1	0.017	0.001	-10000	0	-10000	0	0
ABCG2	-0.14	0.29	-10000	0	-0.55	75	75
EFNA1	-0.005	0.19	-10000	0	-0.5	14	14
FXN	-0.005	0.18	-10000	0	-0.51	11	11
POU5F1	-0.014	0.2	-10000	0	-0.55	23	23
neuron apoptosis	0.008	0.21	0.57	13	-10000	0	13
EP300	0.011	0	-10000	0	-10000	0	0
EGLN3	0.007	0.031	-10000	0	-0.31	4	4
EGLN2	0.009	0.013	-10000	0	-10000	0	0
EGLN1	0.009	0.013	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.021	0.011	-10000	0	-0.23	1	1
VHL	0.01	0.019	-10000	0	-0.42	1	1
ARNT	0.008	0.014	-10000	0	-10000	0	0
SLC2A1	-0.005	0.18	-10000	0	-0.52	11	11
TWIST1	-0.018	0.21	-10000	0	-0.55	35	35
ELK1	0.015	0.01	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.003	0.11	-10000	0	-0.36	6	6
VEGFA	-0.005	0.19	-10000	0	-0.54	10	10
CREBBP	0.01	0.019	-10000	0	-0.42	1	1

×

IL27-mediated signaling events

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
TGFB1	0.004	0.057	-10000	0	-0.4	10	10
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.016	0.1	0.44	6	-10000	0	6
IL27/IL27R/JAK1	-0.016	0.12	-10000	0	-0.72	4	4
TBX21	0.002	0.11	-10000	0	-0.5	7	7
IL12B	0.006	0.013	-10000	0	-0.27	1	1
IL12A	0.002	0.038	-10000	0	-0.21	15	15
IL6ST	-0.073	0.17	-10000	0	-0.42	100	100
IL27RA/JAK1	0.011	0.074	-10000	0	-1.1	2	2
IL27	0.004	0.039	-10000	0	-0.27	10	10
TYK2	0.012	0.004	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.025	0.17	-10000	0	-1.3	9	9
T-helper 2 cell differentiation	0.016	0.1	0.44	6	-10000	0	6
T cell proliferation during immune response	0.016	0.1	0.44	6	-10000	0	6
MAPKKK cascade	-0.016	0.1	-10000	0	-0.44	6	6
STAT3	0.011	0	-10000	0	-10000	0	0
STAT2	0.011	0	-10000	0	-10000	0	0
STAT1	0.01	0.013	-10000	0	-0.28	1	1
IL12RB1	0.002	0.055	-10000	0	-0.33	13	13
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.001	0.11	-10000	0	-0.47	8	8
IL27/IL27R/JAK2/TYK2	-0.016	0.1	-10000	0	-0.45	6	6
positive regulation of T cell mediated cytotoxicity	-0.016	0.1	-10000	0	-0.44	6	6
STAT1 (dimer)	-0.037	0.12	0.39	8	-0.7	5	13
JAK2	0.003	0.056	-10000	0	-0.42	9	9
JAK1	0.008	0.033	-10000	0	-0.42	3	3
STAT2 (dimer)	-0.009	0.097	-10000	0	-0.42	6	6
T cell proliferation	-0.021	0.11	-10000	0	-0.41	15	15
IL12/IL12R/TYK2/JAK2	0.019	0.049	-10000	0	-0.53	1	1
IL17A	-0.027	0.18	-10000	0	-1.3	9	9
mast cell activation	0.016	0.1	0.44	6	-10000	0	6
IFNG	0.001	0.02	-10000	0	-0.076	3	3
T cell differentiation	-0.002	0.004	-10000	0	-0.021	3	3
STAT3 (dimer)	-0.009	0.097	-10000	0	-0.42	6	6
STAT5A (dimer)	-0.009	0.097	-10000	0	-0.42	6	6
STAT4 (dimer)	-0.01	0.097	-10000	0	-0.42	6	6
STAT4	0.01	0.019	-10000	0	-0.42	1	1
T cell activation	-0.007	0.009	0.12	2	-10000	0	2
IL27R/JAK2/TYK2	-0.021	0.12	-10000	0	-0.65	5	5
GATA3	-0.008	0.11	-10000	0	-1.2	4	4
IL18	0.006	0.022	-10000	0	-0.18	7	7
positive regulation of mast cell cytokine production	-0.009	0.096	-10000	0	-0.42	6	6
IL27/EBI3	0.008	0.042	-10000	0	-0.2	19	19
IL27RA	0.003	0.076	-10000	0	-1.2	2	2
IL6	-0.017	0.1	-10000	0	-0.38	38	38
STAT5A	0.011	0	-10000	0	-10000	0	0
monocyte differentiation	0	0	-10000	0	-10000	0	0
IL2	0	0.033	0.46	2	-10000	0	2
IL1B	0.006	0.027	-10000	0	-0.29	4	4
EBI3	0.005	0.042	-10000	0	-0.28	11	11
TNF	-0.01	0.058	-10000	0	-0.19	50	50

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	0.023	0.014	-10000	0	-0.2	2	2
epithelial cell differentiation	-0.001	0.013	-10000	0	-0.19	2	2
CYFIP2	0.008	0.033	-10000	0	-0.42	3	3
ENAH	0.046	0.017	-10000	0	-10000	0	0
EGFR	-0.001	0.068	-10000	0	-0.41	14	14
EPHA2	0.011	0	-10000	0	-10000	0	0
MYO6	0.028	0.014	-10000	0	-0.18	2	2
CTNNB1	0.011	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.02	0.019	-10000	0	-0.23	3	3
AQP5	0.036	0.042	-10000	0	-0.38	3	3
CTNND1	0.011	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.027	0.014	-10000	0	-0.17	2	2
regulation of calcium-dependent cell-cell adhesion	0.022	0.039	-10000	0	-0.2	15	15
EGF	-0.002	0.058	-10000	0	-0.29	20	20
NCKAP1	0.011	0	-10000	0	-10000	0	0
AQP3	-0.004	0.046	-10000	0	-0.45	5	5
cortical microtubule organization	-0.001	0.013	-10000	0	-0.19	2	2
GO:0000145	0.026	0.013	-10000	0	-0.16	2	2
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.024	0.015	-10000	0	-0.19	2	2
MLLT4	0.011	0	-10000	0	-10000	0	0
ARF6/GDP	-0.001	0.013	-10000	0	-10000	0	0
ARF6	0.011	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.026	0.017	-10000	0	-0.2	2	2
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.036	0.013	-10000	0	-10000	0	0
PVRL2	0.011	0	-10000	0	-10000	0	0
ZYX	0.028	0.014	-10000	0	-0.18	2	2
ARF6/GTP	0.029	0.016	-10000	0	-0.18	2	2
CDH1	0.008	0.029	-10000	0	-0.37	3	3
EGFR/EGFR/EGF/EGF	-0.009	0.038	-10000	0	-0.23	7	7
RhoA/GDP	-0.001	0.012	-10000	0	-0.17	2	2
actin cytoskeleton organization	0.031	0.014	-10000	0	-0.17	2	2
IGF-1R heterotetramer	-0.006	0.083	-10000	0	-0.42	20	20
GIT1	0.011	0	-10000	0	-10000	0	0
IGF1R	-0.006	0.083	-10000	0	-0.42	20	20
IGF1	-0.074	0.17	-10000	0	-0.42	102	102
DIAPH1	-0.003	0.04	-10000	0	-0.53	3	3
Wnt receptor signaling pathway	0.001	0.013	0.19	2	-10000	0	2
RHOA	0.011	0	-10000	0	-10000	0	0
RhoA/GTP	-0.001	0.013	-10000	0	-10000	0	0
CTNNA1	0.011	0	-10000	0	-10000	0	0
VCL	0.032	0.014	-10000	0	-0.17	2	2
EFNA1	0.01	0.018	-10000	0	-0.27	2	2
LPP	0.032	0.013	-10000	0	-0.16	2	2
Ephrin A1/EPHA2	-0.001	0.012	-10000	0	-0.16	2	2
SEC6/SEC8	-0.001	0.01	-10000	0	-10000	0	0
MGAT3	0.022	0.039	-10000	0	-0.2	15	15
HGF/MET	-0.034	0.073	-10000	0	-0.18	97	97
HGF	-0.069	0.17	-10000	0	-0.42	96	96
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.023	0.014	-10000	0	-0.2	2	2
actin cable formation	0.059	0.017	-10000	0	-10000	0	0
KIAA1543	0.031	0.026	-10000	0	-0.36	2	2
KIFC3	0.028	0.014	-10000	0	-0.18	2	2
NCK1	0.009	0.027	-10000	0	-0.42	2	2
EXOC3	0.011	0	-10000	0	-10000	0	0
ACTN1	0.028	0.014	-10000	0	-0.18	2	2
NCK1/GIT1	0.015	0.019	-10000	0	-0.29	2	2
mol:GDP	-0.001	0.013	-10000	0	-0.19	2	2
EXOC4	0.011	0	-10000	0	-10000	0	0
STX4	0.028	0.014	-10000	0	-0.18	2	2
PIP5K1C	0.028	0.014	-10000	0	-0.18	2	2
LIMA1	0.011	0	-10000	0	-10000	0	0
ABI1	0.011	0	-10000	0	-10000	0	0
ROCK1	0.045	0.017	-10000	0	-10000	0	0
adherens junction assembly	0.043	0.028	-10000	0	-0.37	2	2
IGF-1R heterotetramer/IGF1	-0.041	0.082	-10000	0	-0.19	112	112
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.016	0	-10000	0	-10000	0	0
MET	0.005	0.045	-10000	0	-0.34	8	8
PLEKHA7	0.027	0.017	-10000	0	-0.18	3	3
mol:GTP	0.025	0.017	-10000	0	-0.2	2	2
establishment of epithelial cell apical/basal polarity	0.045	0.012	-10000	0	-10000	0	0
cortical actin cytoskeleton stabilization	0.023	0.014	-10000	0	-0.2	2	2
regulation of cell-cell adhesion	0.031	0.014	-10000	0	-0.17	2	2
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.023	0.014	-10000	0	-0.2	2	2

×

EPO 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
BCL2L1	0.024	0.11	-10000	0	-0.42	4	4
CRKL	0.021	0.046	-10000	0	-0.24	4	4
mol:DAG	0.024	0.053	-10000	0	-0.25	6	6
HRAS	0.036	0.044	-10000	0	-0.21	2	2
MAPK8	0.019	0.036	-10000	0	-0.21	8	8
RAP1A	0.021	0.046	-10000	0	-0.24	4	4
GAB1	0.019	0.05	-10000	0	-0.24	7	7
MAPK14	0.021	0.027	-10000	0	-0.19	3	3
EPO	0.006	0.035	-10000	0	-0.38	4	4
PLCG1	0.024	0.054	-10000	0	-0.25	6	6
EPOR/TRPC2/IP3 Receptors	0.006	0.039	-10000	0	-0.26	10	10
RAPGEF1	0.011	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.014	0.041	-10000	0	-0.24	9	9
GAB1/SHC/GRB2/SOS1	-0.01	0.031	-10000	0	-0.21	6	6
EPO/EPOR (dimer)	0.011	0.036	-10000	0	-0.19	14	14
IRS2	-0.006	0.084	-10000	0	-0.22	32	32
STAT1	0.023	0.078	-10000	0	-0.35	4	4
STAT5B	0.023	0.068	-10000	0	-0.32	4	4
cell proliferation	0.023	0.033	-10000	0	-0.2	6	6
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.01	0.036	-10000	0	-0.22	10	10
TEC	0.021	0.046	-10000	0	-0.24	4	4
SOCS3	0.006	0.046	-10000	0	-0.42	6	6
STAT1 (dimer)	0.023	0.078	-10000	0	-0.35	4	4
JAK2	0.004	0.057	-10000	0	-0.42	9	9
PIK3R1	0.007	0.038	-10000	0	-0.42	4	4
EPO/EPOR (dimer)/JAK2	0.03	0.051	-10000	0	-0.2	13	13
EPO/EPOR	0.011	0.036	-10000	0	-0.19	14	14
LYN	0.011	0.005	-10000	0	-10000	0	0
TEC/VAV2	0.027	0.045	-10000	0	-0.23	4	4
elevation of cytosolic calcium ion concentration	0.006	0.039	-10000	0	-0.26	10	10
SHC1	0.011	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	0.021	0.032	-10000	0	-0.23	3	3
mol:IP3	0.024	0.053	-10000	0	-0.25	6	6
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.004	0.084	-10000	0	-0.26	19	19
SH2B3	0.01	0.019	-10000	0	-0.41	1	1
NFKB1	0.021	0.029	-10000	0	-0.2	4	4
EPO/EPOR (dimer)/JAK2/SOCS3	-0.007	0.041	0.23	1	-0.21	18	19
PTPN6	0.016	0.048	-10000	0	-0.2	13	13
TEC/VAV2/GRB2	0.032	0.044	-10000	0	-0.22	4	4
EPOR	0.006	0.039	-10000	0	-0.27	10	10
INPP5D	0.01	0.019	-10000	0	-0.42	1	1
mol:GDP	-0.01	0.032	-10000	0	-0.22	6	6
SOS1	0.011	0	-10000	0	-10000	0	0
PLCG2	0.01	0.019	-10000	0	-0.42	1	1
CRKL/CBL/C3G	0.032	0.044	-10000	0	-0.22	4	4
VAV2	0.021	0.046	-10000	0	-0.24	4	4
CBL	0.021	0.046	-10000	0	-0.24	4	4
SHC/Grb2/SOS1	-0.007	0.03	-10000	0	-0.22	4	4
STAT5A	0.023	0.067	-10000	0	-0.28	6	6
GRB2	0.011	0	-10000	0	-10000	0	0
STAT5 (dimer)	0.027	0.099	-10000	0	-0.31	12	12
LYN/PLCgamma2	0.015	0.014	-10000	0	-0.28	1	1
PTPN11	0.011	0	-10000	0	-10000	0	0
BTK	0.019	0.052	-10000	0	-0.25	7	7
BCL2	-0.022	0.25	-10000	0	-0.79	48	48

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.022	0.02	-9999	-0.29	2	2
CRKL	0.011	0	-9999	-10000	0	0
Rac1/GDP	0.008	0	-9999	-10000	0	0
DOCK1	0.006	0.046	-9999	-0.42	6	6
ITGA4	0.008	0.029	-9999	-0.37	3	3
alpha4/beta7 Integrin/MAdCAM1	0.013	0.042	-9999	-0.21	2	2
EPO	0.005	0.035	-9999	-0.38	4	4
alpha4/beta7 Integrin	0.014	0.022	-9999	-0.23	4	4
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.011	0	-9999	-10000	0	0
alpha4/beta1 Integrin	0.014	0.021	-9999	-0.25	3	3
EPO/EPOR (dimer)	0.008	0.036	-9999	-0.2	14	14
lamellipodium assembly	0.024	0.027	-9999	-0.25	4	4
PIK3CA	0.01	0.019	-9999	-0.42	1	1
PI3K	0.013	0.03	-9999	-0.29	5	5
ARF6	0.011	0	-9999	-10000	0	0
JAK2	0.016	0.047	-9999	-0.25	14	14
PXN	0.011	0	-9999	-10000	0	0
PIK3R1	0.007	0.038	-9999	-0.42	4	4
MADCAM1	-0.014	0.077	-9999	-0.27	42	42
cell adhesion	0.013	0.042	-9999	-0.21	2	2
CRKL/CBL	0.016	0	-9999	-10000	0	0
ITGB1	0.011	0	-9999	-10000	0	0
SRC	0.006	0.066	-9999	-0.21	41	41
ITGB7	0.01	0.012	-9999	-0.27	1	1
RAC1	0.011	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0	0.074	-9999	-0.24	41	41
p130Cas/Crk/Dock1	0.021	0.063	-9999	-0.44	2	2
VCAM1	-0.024	0.12	-9999	-0.42	41	41
RHOA	0.011	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.026	0.016	-9999	-0.2	2	2
BCAR1	0.012	0.062	-9999	-0.19	41	41
EPOR	0.005	0.039	-9999	-0.27	10	10
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.011	0	-9999	-10000	0	0
GIT1	0.011	0	-9999	-10000	0	0
Rac1/GTP	-0.001	0.025	-9999	-0.26	4	4

×

IL23-mediated 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	0.055	0.22	-9999	-1.1	12	12
IL23A	0.059	0.2	-9999	-1	9	9
NF kappa B1 p50/RelA/I kappa B alpha	-0.027	0.16	-9999	-0.88	11	11
positive regulation of T cell mediated cytotoxicity	0.06	0.21	-9999	-0.95	12	12
ITGA3	0.061	0.2	-9999	-1.1	6	6
IL17F	0.062	0.15	-9999	-0.64	9	9
IL12B	0.021	0.022	-9999	-0.26	1	1
STAT1 (dimer)	0.056	0.2	-9999	-0.91	12	12
CD4	0.062	0.19	-9999	-0.91	9	9
IL23	0.055	0.2	-9999	-0.98	9	9
IL23R	0.034	0.049	-9999	-10000	0	0
IL1B	0.057	0.22	-9999	-1.1	9	9
T-helper cell lineage commitment	0	0	-9999	-10000	0	0
IL24	0.059	0.19	-9999	-0.94	8	8
TYK2	0.019	0.012	-9999	-10000	0	0
STAT4	0.01	0.019	-9999	-0.42	1	1
STAT3	0.011	0.001	-9999	-10000	0	0
IL18RAP	0.006	0.039	-9999	-0.35	6	6
IL12RB1	0.01	0.058	-9999	-0.34	13	13
PIK3CA	0.01	0.019	-9999	-0.42	1	1
IL12Rbeta1/TYK2	0.018	0.044	-9999	-0.23	13	13
IL23R/JAK2	0.045	0.073	-9999	-10000	0	0
positive regulation of chronic inflammatory response	0.06	0.21	-9999	-0.95	12	12
natural killer cell activation	-0.003	0.004	-9999	-10000	0	0
JAK2	0.018	0.062	-9999	-0.43	9	9
PIK3R1	0.007	0.038	-9999	-0.42	4	4
NFKB1	0.011	0.019	-9999	-0.41	1	1
RELA	0.012	0.002	-9999	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	0.056	0.19	-9999	-0.93	9	9
ALOX12B	0.058	0.19	-9999	-0.92	9	9
CXCL1	0.037	0.25	-9999	-1.1	18	18
T cell proliferation	0.06	0.21	-9999	-0.95	12	12
NFKBIA	0.012	0.002	-9999	-10000	0	0
IL17A	0.063	0.14	-9999	-0.51	8	8
PI3K	-0.015	0.17	-9999	-0.89	12	12
IFNG	0.008	0.014	-9999	-10000	0	0
STAT3 (dimer)	-0.033	0.16	-9999	-0.85	12	12
IL18R1	0.007	0.037	-9999	-0.41	4	4
IL23/IL23R/JAK2/TYK2/SOCS3	0.057	0.15	-9999	-0.73	7	7
IL18/IL18R	0.015	0.039	-9999	-0.24	8	8
macrophage activation	0	0.01	-9999	-0.042	9	9
TNF	0.056	0.21	-9999	-1.1	7	7
STAT3/STAT4	-0.019	0.17	-9999	-0.88	12	12
STAT4 (dimer)	0.056	0.2	-9999	-0.91	12	12
IL18	0.007	0.033	-9999	-0.28	7	7
IL19	0.05	0.19	-9999	-0.94	8	8
STAT5A (dimer)	0.056	0.2	-9999	-0.91	12	12
STAT1	0.01	0.012	-9999	-0.27	1	1
SOCS3	0.006	0.046	-9999	-0.42	6	6
CXCL9	0.048	0.22	-9999	-1.1	11	11
MPO	0.062	0.19	-9999	-0.94	8	8
positive regulation of humoral immune response	0.06	0.21	-9999	-0.95	12	12
IL23/IL23R/JAK2/TYK2	0.059	0.22	-9999	-0.98	12	12
IL6	0.033	0.28	-9999	-1.1	24	24
STAT5A	0.011	0	-9999	-10000	0	0
IL2	-0.006	0.05	-9999	-0.27	17	17
positive regulation of tyrosine phosphorylation of STAT protein	-0.003	0.004	-9999	-10000	0	0
CD3E	0.054	0.23	-9999	-1.1	12	12
keratinocyte proliferation	0.06	0.21	-9999	-0.95	12	12
NOS2	0.055	0.21	-9999	-1	10	10

×

Caspase cascade in apoptosis

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
TOP1	0.015	0.042	-10000	0	-0.27	5	5
ACTA1	0.006	0.051	0.16	4	-0.34	5	9
NUMA1	0.015	0.042	-10000	0	-0.27	5	5
SPTAN1	0.009	0.051	0.17	1	-0.34	5	6
LIMK1	0.009	0.051	0.16	6	-0.34	5	11
BIRC3	0.003	0.057	-10000	0	-0.4	10	10
BIRC2	0.011	0	-10000	0	-10000	0	0
BAX	0.011	0	-10000	0	-10000	0	0
CASP10	-0.001	0.066	-10000	0	-0.29	11	11
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.011	0	-10000	0	-10000	0	0
PTK2	0.015	0.042	-10000	0	-0.27	5	5
DIABLO	0.011	0	-10000	0	-10000	0	0
apoptotic nuclear changes	0.009	0.05	0.17	1	-0.33	5	6
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.011	0	-10000	0	-10000	0	0
GSN	0.005	0.055	-10000	0	-0.34	5	5
MADD	0.011	0	-10000	0	-10000	0	0
TFAP2A	0.05	0.043	-10000	0	-0.55	2	2
BID	0.008	0.032	-10000	0	-0.17	7	7
MAP3K1	0.008	0.021	-10000	0	-0.2	1	1
TRADD	0.011	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.016	0	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	0.009	0.051	0.16	6	-0.34	5	11
CASP9	0.011	0	-10000	0	-10000	0	0
DNA repair	-0.005	0.022	0.14	1	-0.16	6	7
neuron apoptosis	0.019	0.007	-10000	0	-10000	0	0
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.015	0.049	-10000	0	-0.32	5	5
APAF1	0.011	0	-10000	0	-10000	0	0
CASP6	0.023	0.027	-10000	0	-10000	0	0
TRAF2	0.011	0	-10000	0	-10000	0	0
ICAD/CAD	0.014	0.049	-10000	0	-0.32	5	5
CASP7	-0.004	0.034	0.24	9	-10000	0	9
KRT18	0.015	0.033	-10000	0	-0.69	1	1
apoptosis	0.016	0.048	0.18	6	-0.29	4	10
DFFA	0.009	0.051	0.17	1	-0.34	5	6
DFFB	0.009	0.051	0.17	1	-0.34	5	6
PARP1	0.005	0.022	0.16	6	-0.14	1	7
actin filament polymerization	-0.01	0.052	0.3	6	-0.17	1	7
TNF	-0.018	0.086	-10000	0	-0.28	50	50
CYCS	0.009	0.028	-10000	0	-0.16	4	4
SATB1	-0.004	0.079	-10000	0	-0.34	5	5
SLK	0.009	0.051	0.16	6	-0.34	5	11
p15 BID/BAX	0.013	0.028	-10000	0	-0.15	7	7
CASP2	0.032	0.028	-10000	0	-0.3	1	1
JNK cascade	-0.008	0.021	0.2	1	-10000	0	1
CASP3	0.003	0.054	0.17	6	-0.36	5	11
LMNB2	0.033	0.02	-10000	0	-10000	0	0
RIPK1	0.011	0	-10000	0	-10000	0	0
CASP4	0.01	0.019	-10000	0	-0.42	1	1
Mammalian IAPs/DIABLO	0.023	0.031	-10000	0	-0.2	9	9
negative regulation of DNA binding	0.05	0.043	-10000	0	-0.54	2	2
stress fiber formation	0.009	0.05	0.16	6	-0.33	5	11
GZMB	-0.01	0.076	-10000	0	-0.2	64	64
CASP1	0.01	0.031	-10000	0	-0.28	6	6
LMNB1	0.034	0.021	-10000	0	-10000	0	0
APP	0.019	0.007	-10000	0	-10000	0	0
TNFRSF1A	0.011	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.009	0	-10000	0	-10000	0	0
VIM	0.011	0.048	0.18	6	-0.29	4	10
LMNA	0.033	0.02	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.028	0.03	-10000	0	-0.32	1	1
LRDD	0.011	0	-10000	0	-10000	0	0
SREBF1	0.009	0.051	0.17	1	-0.34	5	6
APAF-1/Caspase 9	0	0.017	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0.015	0.041	-10000	0	-0.27	5	5
CFL2	0.01	0.053	0.17	1	-0.31	6	7
GAS2	-0.006	0.075	0.16	5	-0.23	34	39
positive regulation of apoptosis	0.036	0.021	-10000	0	-10000	0	0
PRF1	0.004	0.049	-10000	0	-0.35	9	9

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.033	0.039	-10000	0	-0.24	9	9
BAG4	0.008	0.033	-10000	0	-0.42	3	3
BAD	0.023	0.013	-10000	0	-0.12	1	1
NFKBIA	0.011	0	-10000	0	-10000	0	0
BIRC3	0.002	0.057	-10000	0	-0.4	10	10
BAX	0.023	0.013	-10000	0	-0.12	1	1
EnzymeConsortium:3.1.4.12	0.011	0.01	-10000	0	-0.093	1	1
IKBKB	0.037	0.037	-10000	0	-0.36	1	1
MAP2K2	0.031	0.015	-10000	0	-0.16	1	1
MAP2K1	0.031	0.015	-10000	0	-0.16	1	1
SMPD1	0.015	0.01	-10000	0	-0.088	1	1
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.039	0.038	-10000	0	-0.37	1	1
MAP2K4	0.027	0.015	-10000	0	-0.16	1	1
protein ubiquitination	0.038	0.038	-10000	0	-0.36	1	1
EnzymeConsortium:2.7.1.37	0.035	0.015	-10000	0	-0.16	1	1
response to UV	0	0	-10000	0	-0.001	2	2
RAF1	0.028	0.015	-10000	0	-0.17	1	1
CRADD	0.011	0	-10000	0	-10000	0	0
mol:ceramide	0.018	0.014	-10000	0	-0.13	1	1
I-kappa-B-alpha/RELA/p50/ubiquitin	0.014	0	-10000	0	-10000	0	0
MADD	0.011	0	-10000	0	-10000	0	0
MAP3K1	0.023	0.013	-10000	0	-0.12	1	1
TRADD	0.011	0	-10000	0	-10000	0	0
RELA/p50	0.011	0	-10000	0	-10000	0	0
MAPK3	0.033	0.015	-10000	0	-0.15	1	1
MAPK1	0.033	0.015	-10000	0	-0.15	1	1
p50/RELA/I-kappa-B-alpha	0.016	0	-10000	0	-10000	0	0
FADD	0.033	0.039	-10000	0	-0.24	9	9
KSR1	0.023	0.016	-10000	0	-0.15	2	2
MAPK8	0.029	0.023	-10000	0	-0.15	6	6
TRAF2	0.011	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	0.037	0.037	-10000	0	-0.36	1	1
TNF R/SODD	0.014	0.023	-10000	0	-0.29	3	3
TNF	-0.017	0.086	-10000	0	-0.28	50	50
CYCS	0.033	0.029	0.12	44	-0.11	1	45
IKBKG	0.037	0.037	-10000	0	-0.36	1	1
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.029	0.04	-10000	0	-0.25	9	9
RELA	0.011	0	-10000	0	-10000	0	0
RIPK1	0.011	0	-10000	0	-10000	0	0
AIFM1	0.033	0.029	0.12	44	-0.11	1	45
TNF/TNF R/SODD	0.005	0.051	-10000	0	-0.23	5	5
TNFRSF1A	0.011	0	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.023	0.011	-10000	0	-10000	0	0
NSMAF	0.033	0.038	-10000	0	-0.23	9	9
response to hydrogen peroxide	0	0	-10000	0	-0.001	2	2
BCL2	-0.029	0.12	-10000	0	-0.42	48	48

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.21	0.21	-10000	0	-0.42	265	265
CLTC	0.025	0.002	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.02	0.006	-10000	0	-10000	0	0
Dynamin 2/GTP	0.019	0	-10000	0	-10000	0	0
EXOC4	0.011	0	-10000	0	-10000	0	0
CD59	0.022	0.001	-10000	0	-10000	0	0
CPE	-0.021	0.088	-10000	0	-0.24	71	71
CTNNB1	0.011	0	-10000	0	-10000	0	0
membrane fusion	0.02	0.006	-10000	0	-10000	0	0
CTNND1	0.024	0	-10000	0	-10000	0	0
DNM2	0.011	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.025	0.003	-10000	0	-10000	0	0
TSHR	0.006	0.034	-10000	0	-0.16	20	20
INS	0.009	0.002	-10000	0	-10000	0	0
BIN1	0.007	0.038	-10000	0	-0.42	4	4
mol:Choline	0.02	0.006	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.014	0	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.011	0	-10000	0	-10000	0	0
mol:Ca2+	0.019	0	-10000	0	-10000	0	0
JUP	0.022	0.008	-10000	0	-10000	0	0
ASAP2/amphiphysin II	0.019	0.02	-10000	0	-0.21	4	4
ARF6/GTP	0.008	0	-10000	0	-10000	0	0
CDH1	0.021	0.012	-10000	0	-10000	0	0
clathrin-independent pinocytosis	0.008	0	-10000	0	-10000	0	0
MAPK8IP3	0.011	0	-10000	0	-10000	0	0
positive regulation of endocytosis	0.008	0	-10000	0	-10000	0	0
EXOC2	0.011	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.033	0	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.011	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0	0.006	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.014	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.014	0	-10000	0	-10000	0	0
ACAP1	0.02	0.008	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.018	0.008	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.029	0.004	-10000	0	-10000	0	0
JIP4/KLC1	0.021	0	-10000	0	-10000	0	0
EXOC1	0.011	0	-10000	0	-10000	0	0
exocyst	0.033	0	-10000	0	-10000	0	0
RALA/GTP	0.008	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.014	0	-10000	0	-10000	0	0
receptor recycling	0.008	0	-10000	0	-10000	0	0
CTNNA1	0.024	0	-10000	0	-10000	0	0
NME1	0.015	0	-10000	0	-10000	0	0
clathrin coat assembly	0.025	0.002	-10000	0	-10000	0	0
IL2RA	0.02	0.012	-10000	0	-10000	0	0
VAMP3	0.015	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.081	0.079	-10000	0	-10000	0	0
EXOC6	0.011	0	-10000	0	-10000	0	0
PLD1	0.017	0	-10000	0	-10000	0	0
PLD2	0.017	0.011	-10000	0	-0.24	1	1
EXOC5	0.011	0	-10000	0	-10000	0	0
PIP5K1C	0.025	0.003	-10000	0	-10000	0	0
SDC1	0.004	0.025	-10000	0	-10000	0	0
ARF6/GDP	0.014	0	-10000	0	-10000	0	0
EXOC7	0.011	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	0	0.006	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.02	0.006	-10000	0	-10000	0	0
endocytosis	-0.018	0.02	0.21	4	-10000	0	4
SCAMP2	0.011	0	-10000	0	-10000	0	0
ADRB2	-0.004	0.075	-10000	0	-10000	0	0
EXOC3	0.011	0	-10000	0	-10000	0	0
ASAP2	0.011	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.02	0	-10000	0	-10000	0	0
KLC1	0.011	0	-10000	0	-10000	0	0
AVPR2	-0.032	0.092	-10000	0	-0.21	1	1
RALA	0.011	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0	0.005	-10000	0	-10000	0	0

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.01	0.016	-10000	0	-0.2	3	3
TRAF2/ASK1	0.013	0.019	-10000	0	-0.24	3	3
ATM	0.011	0	-10000	0	-10000	0	0
MAP2K3	0.025	0.018	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.029	0.023	-10000	0	-0.22	3	3
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	-0.001	0.07	-10000	0	-0.42	14	14
TXN	0.007	0	-10000	0	-10000	0	0
CALM1	0.011	0	-10000	0	-10000	0	0
GADD45A	0.011	0	-10000	0	-10000	0	0
GADD45B	0.011	0	-10000	0	-10000	0	0
MAP3K1	0.011	0	-10000	0	-10000	0	0
MAP3K6	0.011	0	-10000	0	-10000	0	0
MAP3K7	0.011	0	-10000	0	-10000	0	0
MAP3K4	0.011	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.014	0.023	-10000	0	-0.29	3	3
TAK1/TAB family	0.001	0.009	0.15	2	-10000	0	2
RAC1/OSM/MEKK3	0.021	0	-10000	0	-10000	0	0
TRAF2	0.011	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.001	0.008	-10000	0	-10000	0	0
TRAF6	0.007	0	-10000	0	-10000	0	0
RAC1	0.011	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.045	0.11	-10000	0	-0.27	100	100
CCM2	0.011	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.016	0.062	-10000	0	-0.14	100	100
MAPK11	0.009	0.027	-10000	0	-0.42	2	2
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.009	0.058	-10000	0	-0.21	3	3
OSM/MEKK3	0.016	0	-10000	0	-10000	0	0
TAOK1	0.012	0.018	-10000	0	-0.28	2	2
TAOK2	0.013	0	-10000	0	-10000	0	0
TAOK3	0.013	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.011	0	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.008	0.033	-10000	0	-0.42	3	3
MAP3K10	0.011	0	-10000	0	-10000	0	0
MAP3K3	0.011	0	-10000	0	-10000	0	0
TRX/ASK1	0.011	0.019	-10000	0	-0.23	3	3
GADD45/MTK1/MTK1	0.019	0.035	-10000	0	-0.19	14	14

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.01	0.019	-9999	-0.42	1	1
PLK4	0.008	0.028	-9999	-0.27	5	5
regulation of centriole replication	0.015	0.023	-9999	-0.19	6	6

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	0.002	0.024	0.21	6	-10000	0	6
DAPP1	0.022	0.054	-10000	0	-0.31	5	5
Src family/SYK family/BLNK-LAT/BTK-ITK	0.044	0.047	-10000	0	-0.49	1	1
mol:DAG	0.045	0.031	0.16	5	-0.18	1	6
HRAS	0.011	0.001	-10000	0	-10000	0	0
RAP1A	0.011	0.001	-10000	0	-10000	0	0
ARF5/GDP	0.025	0.048	-10000	0	-0.32	3	3
PLCG2	0.01	0.019	-10000	0	-0.42	1	1
PLCG1	0.011	0	-10000	0	-10000	0	0
ARF5	0.011	0	-10000	0	-10000	0	0
mol:GTP	0.002	0.023	0.2	6	-10000	0	6
ARF1/GTP	0.002	0.024	0.21	6	-10000	0	6
RHOA	0.011	0	-10000	0	-10000	0	0
YES1	0.011	0	-10000	0	-10000	0	0
RAP1A/GTP	0.023	0.021	0.2	6	-10000	0	6
ADAP1	0.002	0.023	0.2	6	-10000	0	6
ARAP3	0.002	0.023	0.2	6	-10000	0	6
INPPL1	0.011	0	-10000	0	-10000	0	0
PREX1	0.011	0	-10000	0	-10000	0	0
ARHGEF6	-0.001	0.07	-10000	0	-0.42	14	14
ARHGEF7	0.011	0	-10000	0	-10000	0	0
ARF1	0.011	0	-10000	0	-10000	0	0
NRAS	0.011	0.001	-10000	0	-10000	0	0
FYN	0.011	0	-10000	0	-10000	0	0
ARF6	0.011	0	-10000	0	-10000	0	0
FGR	0	0.067	-10000	0	-0.42	13	13
mol:Ca2+	0.031	0.018	-10000	0	-10000	0	0
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	-0.002	0.072	-10000	0	-0.42	15	15
ZAP70	0	0.056	-10000	0	-0.29	18	18
mol:IP3	0.038	0.023	-10000	0	-10000	0	0
LYN	0.011	0	-10000	0	-10000	0	0
ARF1/GDP	0.025	0.048	-10000	0	-0.2	14	14
RhoA/GDP	-0.001	0.026	0.2	5	-0.21	1	6
PDK1/Src/Hsp90	0.022	0	-10000	0	-10000	0	0
BLNK	0.009	0.023	-10000	0	-0.34	2	2
actin cytoskeleton reorganization	0.043	0.037	0.2	5	-0.24	3	8
SRC	0.011	0	-10000	0	-10000	0	0
PLEKHA2	0.022	0.011	-10000	0	-0.23	1	1
RAC1	0.011	0	-10000	0	-10000	0	0
PTEN	0.003	0.043	-10000	0	-0.39	6	6
HSP90AA1	0.011	0	-10000	0	-10000	0	0
ARF6/GTP	0.002	0.024	0.21	6	-10000	0	6
RhoA/GTP	0.027	0.02	0.2	6	-10000	0	6
Src family/SYK family/BLNK-LAT	0.035	0.036	-10000	0	-0.31	1	1
BLK	-0.014	0.077	-10000	0	-0.27	42	42
PDPK1	0.011	0	-10000	0	-10000	0	0
CYTH1	0.002	0.023	0.2	6	-10000	0	6
HCK	0.01	0.012	-10000	0	-0.27	1	1
CYTH3	0.002	0.023	0.2	6	-10000	0	6
CYTH2	0.002	0.023	0.2	6	-10000	0	6
KRAS	0.011	0.012	-10000	0	-0.27	1	1
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.032	0.035	-10000	0	-0.39	3	3
SGK1	-0.001	0.037	0.16	6	-0.42	3	9
INPP5D	0.01	0.019	-10000	0	-0.42	1	1
mol:GDP	0.019	0.05	-10000	0	-0.22	14	14
SOS1	0.011	0	-10000	0	-10000	0	0
SYK	0.01	0.012	-10000	0	-0.27	1	1
ARF6/GDP	-0.001	0.026	0.2	6	-0.21	1	7
mol:PI-3-4-5-P3	0.002	0.026	0.23	6	-10000	0	6
ARAP3/RAP1A/GTP	0.023	0.021	0.2	6	-10000	0	6
VAV1	0.007	0.034	-10000	0	-0.3	6	6
mol:PI-3-4-P2	0.017	0.013	-10000	0	-0.29	1	1
RAS family/GTP/PI3K Class I	0.024	0.009	-10000	0	-10000	0	0
PLEKHA1	0.022	0.011	-10000	0	-0.23	1	1
Rac1/GDP	0.025	0.048	-10000	0	-0.2	14	14
LAT	0.011	0	-10000	0	-10000	0	0
Rac1/GTP	0.017	0.07	-10000	0	-0.27	26	26
ITK	-0.002	0.036	0.2	6	-10000	0	6
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.052	0.038	0.18	5	-0.24	1	6
LCK	0.008	0.031	-10000	0	-0.3	5	5
BTK	0	0.028	0.2	6	-0.17	4	10

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.056	0.034	-9999	-10000	0	0
ERC1	0.011	0	-9999	-10000	0	0
RIP2/NOD2	0.015	0.008	-9999	-0.18	1	1
NFKBIA	0.034	0.01	-9999	-10000	0	0
BIRC2	0.011	0	-9999	-10000	0	0
IKBKB	0.011	0	-9999	-10000	0	0
RIPK2	0.011	0	-9999	-10000	0	0
IKBKG	0.036	0.002	-9999	-10000	0	0
IKK complex/A20	0.052	0.02	-9999	-10000	0	0
NEMO/A20/RIP2	0.011	0	-9999	-10000	0	0
XPO1	0.011	0	-9999	-10000	0	0
NEMO/ATM	0.04	0.001	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.011	0	-9999	-10000	0	0
Exportin 1/RanGTP	0.014	0	-9999	-10000	0	0
IKK complex/ELKS	0	0.001	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0.022	0	-9999	-10000	0	0
NOD2	0.01	0.012	-9999	-0.27	1	1
NFKB1	0.012	0.019	-9999	-0.41	1	1
RELA	0.013	0	-9999	-10000	0	0
MALT1	0.011	0	-9999	-10000	0	0
cIAP1/UbcH5C	0.016	0	-9999	-10000	0	0
ATM	0.011	0	-9999	-10000	0	0
TNF/TNFR1A	-0.003	0.058	-9999	-0.18	50	50
TRAF6	0.011	0	-9999	-10000	0	0
PRKCA	-0.017	0.1	-9999	-0.42	33	33
CHUK	0.011	0	-9999	-10000	0	0
UBE2D3	0.011	0	-9999	-10000	0	0
TNF	-0.018	0.086	-9999	-0.28	50	50
NF kappa B1 p50/RelA	0.03	0.011	-9999	-0.22	1	1
BCL10	0.011	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.034	0.01	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.013	0	-9999	-10000	0	0
TNFRSF1A	0.011	0	-9999	-10000	0	0
IKK complex	0.045	0.001	-9999	-10000	0	0
CYLD	0.011	0	-9999	-10000	0	0
IKK complex/PKC alpha	0.035	0.047	-9999	-10000	0	0

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.007	0.034	-10000	0	-0.33	5	5
positive regulation of NF-kappaB transcription factor activity	0.006	0.051	-10000	0	-0.27	17	17
MAP2K4	0.034	0.018	-10000	0	-10000	0	0
IKBKB	0.011	0	-10000	0	-10000	0	0
TNFRSF10B	0.011	0	-10000	0	-10000	0	0
TNFRSF10A	0.009	0.027	-10000	0	-0.42	2	2
SMPD1	0.014	0.012	-10000	0	-0.16	2	2
IKBKG	0.011	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.001	0.065	-10000	0	-0.42	12	12
TRAIL/TRAILR2	0.014	0.024	-10000	0	-0.22	5	5
TRAIL/TRAILR3	0.012	0.033	-10000	0	-0.24	8	8
TRAIL/TRAILR1	0.012	0.03	-10000	0	-0.24	7	7
TRAIL/TRAILR4	0.006	0.051	-10000	0	-0.27	17	17
TRAIL/TRAILR1/DAP3/GTP	0.018	0.023	-10000	0	-0.21	4	4
IKK complex	-0.001	0.006	-10000	0	-10000	0	0
RIPK1	0.011	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.008	0	-10000	0	-10000	0	0
MAPK3	0.015	0.024	-10000	0	-0.22	5	5
MAP3K1	0.031	0.017	-10000	0	-0.2	2	2
TRAILR4 (trimer)	0.001	0.064	-10000	0	-0.42	12	12
TRADD	0.011	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.009	0.027	-10000	0	-0.42	2	2
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.027	0.02	-10000	0	-0.19	4	4
CFLAR	0.011	0	-10000	0	-10000	0	0
MAPK1	0.015	0.024	-10000	0	-0.22	5	5
TRAIL/TRAILR1/FADD/TRADD/RIP	0.029	0.022	-10000	0	-0.18	4	4
mol:ceramide	0.014	0.012	-10000	0	-0.16	2	2
FADD	0.011	0	-10000	0	-10000	0	0
MAPK8	0.036	0.026	-10000	0	-10000	0	0
TRAF2	0.011	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.008	0.033	-10000	0	-0.42	3	3
CHUK	0.011	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	0.019	0.025	-10000	0	-0.23	4	4
DAP3	0.011	0	-10000	0	-10000	0	0
CASP10	0.003	0.044	0.22	12	-0.39	2	14
JNK cascade	0.006	0.051	-10000	0	-0.27	17	17
TRAIL (trimer)	0.007	0.034	-10000	0	-0.33	5	5
TNFRSF10C	0.008	0.033	-10000	0	-0.42	3	3
TRAIL/TRAILR1/DAP3/GTP/FADD	0.023	0.021	-10000	0	-0.19	4	4
TRAIL/TRAILR2/FADD	0.02	0.02	-10000	0	-0.23	2	2
cell death	0.014	0.012	-10000	0	-0.16	2	2
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.028	0.014	-10000	0	-0.19	2	2
TRAILR2 (trimer)	0.011	0	-10000	0	-10000	0	0
CASP8	0.001	0.007	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.03	0.017	-10000	0	-0.18	2	2

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	0.007	0.031	-9999	-0.22	3	3
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.031	0.025	-9999	-0.24	2	2
SUMO1	0.011	0	-9999	-10000	0	0
ZFPM1	0.009	0.027	-9999	-0.42	2	2
NPC/RanGAP1/SUMO1/Ubc9	0.017	0	-9999	-10000	0	0
FKBP3	0.011	0	-9999	-10000	0	0
Histones	0.03	0.019	-9999	-10000	0	0
YY1/LSF	0.017	0.041	-9999	-0.2	17	17
SMG5	0.011	0	-9999	-10000	0	0
RAN	0.011	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	0.019	0.025	-9999	-0.2	2	2
I kappa B alpha/HDAC1	0.019	0.02	-9999	-10000	0	0
SAP18	0.011	0	-9999	-10000	0	0
RELA	0.023	0.023	-9999	-0.19	3	3
HDAC1/Smad7	0.021	0.011	-9999	-0.23	1	1
RANGAP1	0.011	0	-9999	-10000	0	0
HDAC3/TR2	0.019	0.02	-9999	-10000	0	0
NuRD/MBD3 Complex	0.036	0.011	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.026	0.023	-9999	-0.17	4	4
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.029	0.12	-9999	-0.42	48	48
GATA1	0.006	0.005	-9999	-10000	0	0
Mad/Max	0.016	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.042	0.016	-9999	-10000	0	0
RBBP7	0.011	0	-9999	-10000	0	0
NPC	0.006	0	-9999	-10000	0	0
RBBP4	0.009	0.027	-9999	-0.42	2	2
MAX	0.011	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.011	0	-9999	-10000	0	0
NFKBIA	0.015	0.023	-9999	-10000	0	0
KAT2B	0.002	0.059	-9999	-0.42	10	10
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.033	0.012	-9999	-10000	0	0
SIN3 complex	0.027	0	-9999	-10000	0	0
SMURF1	0.011	0	-9999	-10000	0	0
CHD3	0.011	0	-9999	-10000	0	0
SAP30	0.011	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.011	0	-9999	-10000	0	0
YY1/HDAC3	0.024	0.032	-9999	-10000	0	0
YY1/HDAC2	0.02	0.032	-9999	-0.19	11	11
YY1/HDAC1	0.02	0.032	-9999	-0.19	11	11
NuRD/MBD2 Complex (MeCP1)	0.036	0.011	-9999	-10000	0	0
PPARG	0.008	0.069	-9999	-0.25	31	31
HDAC8/hEST1B	0.022	0	-9999	-10000	0	0
UBE2I	0.011	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.011	0	-9999	-10000	0	0
TNFRSF1A	0.011	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.019	0.02	-9999	-10000	0	0
MBD3L2	0.002	0.004	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.021	0.011	-9999	-0.23	1	1
CREBBP	0.01	0.019	-9999	-0.42	1	1
NuRD/MBD3/MBD3L2 Complex	0.039	0.011	-9999	-10000	0	0
HDAC1	0.011	0	-9999	-10000	0	0
HDAC3	0.015	0.023	-9999	-0.16	2	2
HDAC2	0.011	0	-9999	-10000	0	0
YY1	0.018	0.037	-9999	-0.23	11	11
HDAC8	0.011	0	-9999	-10000	0	0
SMAD7	0.01	0.019	-9999	-0.42	1	1
NCOR2	0.011	0	-9999	-10000	0	0
MXD1	0.011	0	-9999	-10000	0	0
STAT3	0.019	0.013	-9999	-0.27	1	1
NFKB1	0.01	0.019	-9999	-0.42	1	1
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.011	0	-9999	-10000	0	0
YY1/LSF/HDAC1	0.022	0.037	-9999	-0.18	17	17
YY1/SAP30/HDAC1	0.025	0.029	-9999	-0.17	11	11
EP300	0.011	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.019	0.013	-9999	-0.27	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.015	0.023	-9999	-10000	0	0
histone deacetylation	0.036	0.011	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.026	0.021	-9999	-0.18	1	1
nuclear export	-0.021	0	-9999	-10000	0	0
PRKACA	0.011	0	-9999	-10000	0	0
GATAD2B	0.011	0	-9999	-10000	0	0
GATAD2A	0.011	0	-9999	-10000	0	0
GATA2/HDAC3	-0.002	0.07	-9999	-0.21	48	48
GATA1/HDAC1	0.012	0.004	-9999	-10000	0	0
GATA1/HDAC3	0.008	0.021	-9999	-10000	0	0
CHD4	0.011	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.003	0.058	-9999	-0.18	50	50
SIN3/HDAC complex/Mad/Max	0.036	0.011	-9999	-10000	0	0
NuRD Complex	0.042	0.011	-9999	-10000	0	0
positive regulation of chromatin silencing	0.029	0.018	-9999	-10000	0	0
SIN3B	0.011	0	-9999	-10000	0	0
MTA2	0.011	0	-9999	-10000	0	0
SIN3A	0.011	0	-9999	-10000	0	0
XPO1	0.011	0	-9999	-10000	0	0
SUMO1/HDAC1	0.024	0	-9999	-10000	0	0
HDAC complex	0.027	0.014	-9999	-0.2	2	2
GATA1/Fog1	0.011	0.019	-9999	-0.29	2	2
FKBP25/HDAC1/HDAC2	0.022	0	-9999	-10000	0	0
TNF	-0.018	0.086	-9999	-0.28	50	50
negative regulation of cell growth	0.036	0.011	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.036	0.011	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.026	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.026	0.024	-9999	-0.26	2	2
SIN3/HDAC complex/NCoR1	0.034	0.012	-9999	-10000	0	0
TFCP2	0.006	0.046	-9999	-0.42	6	6
NR2C1	0.011	0	-9999	-10000	0	0
MBD3	0.011	0	-9999	-10000	0	0
MBD2	0.011	0	-9999	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

Figure 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
CRKL	0.011	0	-10000	0	-10000	0	0
Rac1/GDP	0	0.003	-10000	0	-10000	0	0
DOCK1	0.006	0.046	-10000	0	-0.42	6	6
ITGA4	0.008	0.029	-10000	0	-0.37	3	3
RAC1	0.011	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	0.014	0.022	-10000	0	-0.23	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.011	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.02	0.017	-10000	0	-0.23	2	2
alpha4/beta7 Integrin/Paxillin	0.025	0.017	-10000	0	-0.2	2	2
lamellipodium assembly	-0.005	0.046	-10000	0	-0.42	5	5
PIK3CA	0.01	0.019	-10000	0	-0.42	1	1
PI3K	0.013	0.03	-10000	0	-0.29	5	5
ARF6	0.011	0	-10000	0	-10000	0	0
TLN1	0.011	0	-10000	0	-10000	0	0
PXN	0.017	0	-10000	0	-10000	0	0
PIK3R1	0.007	0.038	-10000	0	-0.42	4	4
ARF6/GTP	-0.001	0.011	-10000	0	-10000	0	0
cell adhesion	0.03	0.015	-10000	0	-0.18	2	2
CRKL/CBL	0.016	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.025	0.016	-10000	0	-0.2	2	2
ITGB1	0.011	0	-10000	0	-10000	0	0
ITGB7	0.01	0.012	-10000	0	-0.27	1	1
ARF6/GDP	0	0.003	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.013	0.063	-10000	0	-0.2	41	41
p130Cas/Crk/Dock1	0.019	0.027	-10000	0	-0.23	6	6
VCAM1	-0.024	0.12	-10000	0	-0.42	41	41
alpha4/beta1 Integrin/Paxillin/Talin	0.031	0.015	-10000	0	-0.18	2	2
alpha4/beta1 Integrin/Paxillin/GIT1	0.031	0.015	-10000	0	-0.18	2	2
BCAR1	0.011	0	-10000	0	-10000	0	0
mol:GDP	-0.03	0.015	0.18	2	-10000	0	2
CBL	0.011	0	-10000	0	-10000	0	0
PRKACA	0.011	0	-10000	0	-10000	0	0
GIT1	0.011	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.031	0.015	-10000	0	-0.18	2	2
Rac1/GTP	-0.006	0.052	-10000	0	-0.47	5	5

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.008	0.033	-9999	-0.42	3	3
Caspase 8 (4 units)	0.03	0.031	-9999	-10000	0	0
NEF	0.002	0.017	-9999	-0.16	3	3
NFKBIA	0.011	0.013	-9999	-10000	0	0
BIRC3	0.025	0.064	-9999	-0.44	9	9
CYCS	0.034	0.032	-9999	-0.2	3	3
RIPK1	0.011	0	-9999	-10000	0	0
CD247	0.011	0.029	-9999	-0.38	2	2
MAP2K7	0.036	0.031	-9999	-10000	0	0
protein ubiquitination	0.049	0.024	-9999	-10000	0	0
CRADD	0.011	0	-9999	-10000	0	0
DAXX	0.011	0	-9999	-10000	0	0
FAS	0.006	0.042	-9999	-0.42	5	5
BID	0.03	0.034	-9999	-0.22	3	3
NF-kappa-B/RelA/I kappa B alpha	0.025	0.036	-9999	-0.23	10	10
TRADD	0.011	0	-9999	-10000	0	0
MAP3K5	0.008	0.033	-9999	-0.42	3	3
CFLAR	0.011	0	-9999	-10000	0	0
FADD	0.011	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.025	0.036	-9999	-0.23	10	10
MAPK8	0.039	0.036	-9999	-10000	0	0
APAF1	0.011	0	-9999	-10000	0	0
TRAF1	0.011	0	-9999	-10000	0	0
TRAF2	0.011	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.025	0.035	-9999	-0.22	4	4
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.044	0.028	-9999	-0.24	2	2
CHUK	0.05	0.026	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.028	0.027	-9999	-0.18	8	8
TCRz/NEF	0.011	0.033	-9999	-0.28	5	5
TNF	-0.018	0.086	-9999	-0.28	50	50
FASLG	0.014	0.053	-9999	-0.3	12	12
NFKB1	0.011	0.023	-9999	-0.41	1	1
TNFR1A/BAG4/TNF-alpha	0.004	0.052	-9999	-0.23	5	5
CASP6	-0.003	0.021	-9999	-10000	0	0
CASP7	0.053	0.073	-9999	-0.46	9	9
RELA	0.011	0.013	-9999	-10000	0	0
CASP2	0.011	0	-9999	-10000	0	0
CASP3	0.053	0.073	-9999	-0.46	9	9
TNFRSF1A	0.011	0	-9999	-10000	0	0
TNFR1A/BAG4	0.014	0.023	-9999	-0.29	3	3
CASP8	0.011	0	-9999	-10000	0	0
CASP9	0.011	0	-9999	-10000	0	0
MAP3K14	0.047	0.027	-9999	-10000	0	0
APAF-1/Caspase 9	-0.007	0.042	-9999	-0.3	9	9
BCL2	0.025	0.068	-9999	-0.3	5	5

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.024	0.026	-9999	-0.57	1	1
VEGFR1 homodimer/NRP1	0.017	0.026	-9999	-0.57	1	1
mol:DAG	0.029	0.025	-9999	-0.51	1	1
VEGFR1 homodimer/NRP1/VEGFR 121	0.022	0.024	-9999	-0.53	1	1
CaM/Ca2+	0.033	0.024	-9999	-0.48	1	1
HIF1A	0.016	0.014	-9999	-0.31	1	1
GAB1	0.007	0.038	-9999	-0.42	4	4
AKT1	0.04	0.033	-9999	-0.46	1	1
PLCG1	0.029	0.025	-9999	-0.52	1	1
NOS3	0.045	0.037	-9999	-0.75	1	1
CBL	0.011	0	-9999	-10000	0	0
mol:NO	0.045	0.035	-9999	-0.71	1	1
FLT1	0.023	0.03	-9999	-0.66	1	1
PGF	0.01	0.012	-9999	-0.27	1	1
VEGFR1 homodimer/NRP2/VEGFR121	0.018	0.056	-9999	-0.52	1	1
CALM1	0.011	0	-9999	-10000	0	0
PIK3CA	0.01	0.019	-9999	-0.42	1	1
eNOS/Hsp90	0.05	0.034	-9999	-0.68	1	1
endothelial cell proliferation	0.016	0.074	-9999	-0.38	6	6
mol:Ca2+	0.029	0.025	-9999	-0.51	1	1
MAPK3	0.024	0.055	-9999	-0.45	1	1
MAPK1	0.024	0.055	-9999	-0.45	1	1
PIK3R1	0.007	0.038	-9999	-0.42	4	4
PLGF homodimer	0.01	0.012	-9999	-0.27	1	1
PRKACA	0.011	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.082	0.18	-9999	-0.42	111	111
VEGFA homodimer	0.011	0	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0.024	0.026	-9999	-0.57	1	1
platelet activating factor biosynthetic process	0.028	0.053	-9999	-0.43	1	1
PI3K	0.032	0.032	-9999	-0.49	1	1
PRKCA	0.019	0.058	-9999	-0.48	1	1
PRKCB	0.02	0.059	-9999	-0.67	1	1
VEGFR1 homodimer/PLGF homodimer	0.024	0.027	-9999	-0.57	1	1
VEGFA	0.011	0	-9999	-10000	0	0
VEGFB	0.011	0	-9999	-10000	0	0
mol:IP3	0.029	0.025	-9999	-0.51	1	1
RASA1	0.027	0.033	-9999	-0.52	1	1
NRP2	-0.011	0.094	-9999	-0.42	26	26
VEGFR1 homodimer	0.022	0.03	-9999	-0.65	1	1
VEGFB homodimer	0.011	0	-9999	-10000	0	0
NCK1	0.009	0.027	-9999	-0.42	2	2
eNOS/Caveolin-1	0.008	0.088	-9999	-0.84	1	1
PTPN11	0.011	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.031	0.031	-9999	-0.48	1	1
mol:L-citrulline	0.045	0.035	-9999	-0.71	1	1
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.035	0.023	-9999	-0.49	1	1
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.029	0.028	-9999	-0.52	1	1
CD2AP	0.011	0	-9999	-10000	0	0
PI3K/GAB1	0.035	0.035	-9999	-0.46	1	1
PDPK1	0.035	0.03	-9999	-0.45	1	1
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.03	0.024	-9999	-0.52	1	1
mol:NADP	0.045	0.035	-9999	-0.71	1	1
HSP90AA1	0.011	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.034	0.023	-9999	-0.48	1	1
VEGFR1 homodimer/NRP2	0.012	0.061	-9999	-0.24	27	27

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.035	0.029	-10000	0	-0.22	6	6
adherens junction organization	0.032	0.028	-10000	0	-0.35	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.035	0.042	-10000	0	-0.39	2	2
FMN1	0.028	0.034	-10000	0	-0.34	2	2
mol:IP3	0.029	0.025	-10000	0	-0.19	6	6
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.027	0.027	-10000	0	-0.36	2	2
CTNNB1	0.01	0.001	-10000	0	-10000	0	0
AKT1	0.034	0.026	-10000	0	-0.33	1	1
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.032	0.029	-10000	0	-0.42	2	2
CTNND1	0.011	0.001	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.031	0.026	-10000	0	-0.33	2	2
VASP	0.031	0.026	-10000	0	-0.34	2	2
ZYX	0.031	0.026	-10000	0	-0.34	2	2
JUB	0.031	0.026	-10000	0	-0.34	2	2
EGFR(dimer)	0.027	0.046	-10000	0	-0.21	14	14
E-cadherin/beta catenin-gamma catenin	0.019	0.023	-10000	0	-0.26	3	3
mol:PI-3-4-5-P3	0.029	0.028	-10000	0	-0.2	6	6
PIK3CA	0.01	0.019	-10000	0	-0.42	1	1
PI3K	0.03	0.028	-10000	0	-0.21	6	6
FYN	0.033	0.03	-10000	0	-0.25	1	1
mol:Ca2+	0.029	0.025	-10000	0	-0.19	6	6
JUP	0.01	0.019	-10000	0	-0.41	1	1
PIK3R1	0.008	0.038	-10000	0	-0.42	4	4
mol:DAG	0.029	0.025	-10000	0	-0.19	6	6
CDH1	0.008	0.029	-10000	0	-0.37	3	3
RhoA/GDP	0.035	0.042	-10000	0	-0.39	2	2
establishment of polarity of embryonic epithelium	0.031	0.026	-10000	0	-0.33	2	2
SRC	0.011	0	-10000	0	-10000	0	0
RAC1	0.011	0	-10000	0	-10000	0	0
RHOA	0.011	0	-10000	0	-10000	0	0
EGFR	-0.001	0.068	-10000	0	-0.41	14	14
CASR	0.026	0.034	-10000	0	-0.28	1	1
RhoA/GTP	-0.002	0.019	-10000	0	-0.27	1	1
AKT2	0.034	0.026	-10000	0	-0.19	6	6
actin cable formation	0.032	0.033	-10000	0	-0.33	2	2
apoptosis	-0.032	0.028	0.21	6	-10000	0	6
CTNNA1	0.011	0.001	-10000	0	-10000	0	0
mol:GDP	0.03	0.044	-10000	0	-0.42	2	2
PIP5K1A	0.031	0.026	-10000	0	-0.34	2	2
PLCG1	0.03	0.026	-10000	0	-0.2	6	6
Rac1/GTP	-0.005	0.037	-10000	0	-0.34	3	3
homophilic cell adhesion	0.001	0.001	-10000	0	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.011	0	-9999	-10000	0	0
ITGB7	0.01	0.012	-9999	-0.27	1	1
ITGA4	0.008	0.029	-9999	-0.37	3	3
alpha4/beta7 Integrin	0.014	0.022	-9999	-0.23	4	4
alpha4/beta1 Integrin	0.014	0.021	-9999	-0.25	3	3

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.01	0.019	-9999	-0.42	1	1
SMAD2	0.011	0	-9999	-10000	0	0
SMAD3	0.03	0.017	-9999	-10000	0	0
SMAD3/SMAD4	0.035	0.02	-9999	-0.34	1	1
SMAD4/Ubc9/PIASy	0.021	0.011	-9999	-0.23	1	1
SMAD2/SMAD2/SMAD4	0.027	0.024	-9999	-10000	0	0
PPM1A	0.011	0	-9999	-10000	0	0
CALM1	0.011	0	-9999	-10000	0	0
SMAD2/SMAD4	0.016	0.01	-9999	-0.2	1	1
MAP3K1	0.011	0	-9999	-10000	0	0
TRAP-1/SMAD4	0.01	0.04	-9999	-0.29	9	9
MAPK3	0.011	0	-9999	-10000	0	0
MAPK1	0.011	0	-9999	-10000	0	0
NUP214	0.011	0	-9999	-10000	0	0
CTDSP1	0.011	0	-9999	-10000	0	0
CTDSP2	0.011	0	-9999	-10000	0	0
CTDSPL	0.011	0	-9999	-10000	0	0
KPNB1	0.011	0	-9999	-10000	0	0
TGFBRAP1	0.004	0.053	-9999	-0.42	8	8
UBE2I	0.011	0	-9999	-10000	0	0
NUP153	0.01	0.019	-9999	-0.42	1	1
KPNA2	0.002	0.048	-9999	-0.27	15	15
PIAS4	0.011	0	-9999	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.031	0.013	-10000	0	-10000	0	0
regulation of axonogenesis	-0.022	0.008	-10000	0	-10000	0	0
myoblast fusion	-0.016	0.013	-10000	0	-10000	0	0
mol:GTP	0.008	0.006	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.02	0.042	0.22	15	-10000	0	15
ARF1/GTP	0	0.002	-10000	0	-10000	0	0
mol:GM1	0.008	0.005	-10000	0	-10000	0	0
mol:Choline	0.021	0.011	-10000	0	-0.22	1	1
lamellipodium assembly	0.002	0.012	-10000	0	-10000	0	0
MAPK3	0.022	0.008	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.021	0.042	-10000	0	-0.22	15	15
ARF1	0.011	0	-10000	0	-10000	0	0
ARF6/GDP	0.016	0.013	-10000	0	-10000	0	0
ARF1/GDP	0.022	0.012	-10000	0	-10000	0	0
ARF6	0.01	0.003	-10000	0	-10000	0	0
RAB11A	0.011	0	-10000	0	-10000	0	0
TIAM1	0	0.072	-10000	0	-0.42	15	15
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.022	0.008	-10000	0	-10000	0	0
actin filament bundle formation	-0.02	0.01	-10000	0	-10000	0	0
KALRN	-0.001	0.024	-10000	0	-0.21	5	5
RAB11FIP3/RAB11A	0.016	0	-10000	0	-10000	0	0
RhoA/GDP	0.02	0.01	-10000	0	-10000	0	0
NME1	0.012	0.001	-10000	0	-10000	0	0
Rac1/GDP	0.02	0.01	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.008	0.006	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	0.002	0.012	-10000	0	-10000	0	0
RAC1	0.011	0	-10000	0	-10000	0	0
liver development	0.008	0.006	-10000	0	-10000	0	0
ARF6/GTP	0.008	0.006	-10000	0	-10000	0	0
RhoA/GTP	0	0.002	-10000	0	-10000	0	0
mol:GDP	0.002	0.013	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	0.021	0.005	-10000	0	-10000	0	0
RHOA	0.011	0	-10000	0	-10000	0	0
PLD1	0.016	0.004	-10000	0	-10000	0	0
RAB11FIP3	0.011	0	-10000	0	-10000	0	0
tube morphogenesis	0.002	0.012	-10000	0	-10000	0	0
ruffle organization	0.022	0.008	-10000	0	-10000	0	0
regulation of epithelial cell migration	0.008	0.006	-10000	0	-10000	0	0
PLD2	0.016	0.013	-10000	0	-0.26	1	1
PIP5K1A	0.022	0.008	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.021	0.011	-10000	0	-0.22	1	1
Rac1/GTP	0.002	0.012	-10000	0	-10000	0	0

×

Atypical NF-kappaB pathway

Figure S125. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S125. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.015	0.008	-9999	-0.18	1	1
FBXW11	0.011	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.02	0.011	-9999	-0.24	1	1
NF kappa B1 p50/RelA/I kappa B alpha	0.036	0.012	-9999	-10000	0	0
NFKBIA	0.022	0.01	-9999	-0.18	1	1
MAPK14	0.011	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.02	0.011	-9999	-0.23	1	1
ARRB2	0.013	0	-9999	-10000	0	0
REL	0.011	0.001	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.02	0.013	-9999	-0.23	1	1
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.02	0.011	-9999	-0.23	1	1
PIK3CA	0.01	0.019	-9999	-0.42	1	1
NF kappa B1 p50 dimer	0.015	0.013	-9999	-0.29	1	1
PIK3R1	0.007	0.038	-9999	-0.42	4	4
NFKB1	0.017	0.013	-9999	-0.29	1	1
RELA	0.011	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.027	0.011	-9999	-0.18	1	1
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.039	0.012	-9999	-10000	0	0
SRC	0.011	0	-9999	-10000	0	0
PI3K	0.013	0.03	-9999	-0.29	5	5
NF kappa B1 p50/RelA	0.027	0.011	-9999	-0.18	1	1
IKBKB	0.011	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.011	0	-9999	-10000	0	0
SYK	0.01	0.012	-9999	-0.27	1	1
I kappa B alpha/PIK3R1	0.025	0.02	-9999	-0.18	5	5
cell death	0.037	0.011	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	0.02	0.011	-9999	-0.24	1	1
LCK	0.008	0.031	-9999	-0.3	5	5
BCL3	0.01	0.012	-9999	-0.27	1	1

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.031	0.026	-9999	-0.38	2	2
KLHL20	-0.002	0.012	-9999	-10000	0	0
CYFIP2	0.008	0.033	-9999	-0.42	3	3
Rac1/GDP	0.046	0.017	-9999	-0.21	2	2
ENAH	0.031	0.027	-9999	-0.38	2	2
AP1M1	0.011	0	-9999	-10000	0	0
RAP1B	0.011	0	-9999	-10000	0	0
RAP1A	0.011	0	-9999	-10000	0	0
CTNNB1	0.011	0	-9999	-10000	0	0
CDC42/GTP	-0.001	0.008	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.002	0.01	-9999	-0.12	2	2
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.026	0.017	-9999	-0.2	2	2
RAPGEF1	0.039	0.023	-9999	-0.33	2	2
CTNND1	0.011	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.026	0.027	-9999	-0.4	2	2
CRK	0.035	0.025	-9999	-0.36	2	2
E-cadherin/gamma catenin/alpha catenin	0.02	0.025	-9999	-0.35	2	2
alphaE/beta7 Integrin	0.015	0.008	-9999	-0.18	1	1
IQGAP1	0.011	0	-9999	-10000	0	0
NCKAP1	0.011	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.021	0	-9999	-10000	0	0
DLG1	0.031	0.026	-9999	-0.38	2	2
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.01	-9999	-10000	0	0
MLLT4	0.011	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.014	0.039	-9999	-0.21	15	15
PI3K	-0.001	0.012	-9999	-10000	0	0
ARF6	0.011	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	0.014	0.029	-9999	-0.33	3	3
TIAM1	-0.002	0.072	-9999	-0.42	15	15
E-cadherin(dimer)/Ca2+	0.025	0.015	-9999	-0.19	2	2
AKT1	-0.001	0.007	-9999	-10000	0	0
PIK3R1	0.007	0.038	-9999	-0.42	4	4
CDH1	0.008	0.029	-9999	-0.37	3	3
RhoA/GDP	0.046	0.017	-9999	-0.21	2	2
actin cytoskeleton organization	0.032	0.015	-9999	-10000	0	0
CDC42/GDP	0.046	0.017	-9999	-0.21	2	2
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.018	0.022	-9999	-0.31	2	2
ITGB7	0.01	0.012	-9999	-0.27	1	1
RAC1	0.011	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.027	0.016	-9999	-0.2	2	2
E-cadherin/Ca2+/beta catenin/alpha catenin	0.018	0.015	-9999	-0.2	2	2
mol:GDP	0.044	0.019	-9999	-0.25	2	2
CDC42/GTP/IQGAP1	0.014	0	-9999	-10000	0	0
JUP	0.01	0.019	-9999	-0.42	1	1
p120 catenin/RhoA/GDP	0.043	0.018	-9999	-0.21	2	2
RAC1/GTP/IQGAP1	0.014	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0.016	0	-9999	-10000	0	0
RHOA	0.011	0	-9999	-10000	0	0
CDC42	0.011	0	-9999	-10000	0	0
CTNNA1	0.011	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.026	0.01	-9999	-10000	0	0
NME1	0.011	0	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.031	0.027	-9999	-0.38	2	2
regulation of cell-cell adhesion	-0.001	0.008	-9999	-10000	0	0
WASF2	-0.001	0.005	-9999	-10000	0	0
Rap1/GTP	-0.001	0.01	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.03	0.022	-9999	-0.29	2	2
CCND1	0.03	0.012	-9999	-10000	0	0
VAV2	0.039	0.025	-9999	-0.35	2	2
RAP1/GDP	0.041	0.016	-9999	-10000	0	0
adherens junction assembly	0.03	0.027	-9999	-0.37	2	2
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.011	0	-9999	-10000	0	0
PIP5K1C	0.011	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.034	0.022	-9999	-0.27	2	2
E-cadherin/beta catenin	-0.001	0.019	-9999	-0.3	2	2
mol:GTP	0	0	-9999	-10000	0	0
SRC	0.031	0.026	-9999	-0.38	2	2
PIK3CA	0.01	0.019	-9999	-0.42	1	1
Rac1/GTP	-0.003	0.017	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin	0.021	0.017	-9999	-0.23	2	2
ITGAE	0.011	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.026	0.027	-9999	-0.41	2	2

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.02	0.025	-9999	-0.35	2	2
E-cadherin/beta catenin	0.014	0.021	-9999	-0.25	3	3
CTNNB1	0.011	0	-9999	-10000	0	0
JUP	0.01	0.019	-9999	-0.42	1	1
CDH1	0.008	0.029	-9999	-0.37	3	3

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.037	0.009	-9999	-10000	0	0
CLOCK	0.013	0.001	-9999	-10000	0	0
TIMELESS/CRY2	0.033	0.009	-9999	-10000	0	0
DEC1/BMAL1	0.01	0.014	-9999	-0.29	1	1
ATR	0.011	0	-9999	-10000	0	0
NR1D1	0.032	0.009	-9999	-10000	0	0
ARNTL	0.012	0.019	-9999	-0.41	1	1
TIMELESS	0.032	0.011	-9999	-10000	0	0
NPAS2	0.009	0.042	-9999	-0.41	5	5
CRY2	0.011	0	-9999	-10000	0	0
mol:CO	-0.011	0.002	-9999	-10000	0	0
CHEK1	0.011	0	-9999	-10000	0	0
mol:HEME	0.011	0.002	-9999	-10000	0	0
PER1	0.011	0	-9999	-10000	0	0
BMAL/CLOCK/NPAS2	0.032	0.028	-9999	-0.22	6	6
BMAL1/CLOCK	0.039	0.018	-9999	-10000	0	0
S phase of mitotic cell cycle	0.037	0.009	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	0.038	0.009	-9999	-10000	0	0
mol:NADPH	0.011	0.002	-9999	-10000	0	0
PER1/TIMELESS	0.033	0.009	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	0.001	0.004	-9999	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
HDAC1	0.011	-9999	-9999
Ran/GTP/Exportin 1/HDAC4	0	-9999	-9999
MDM2/SUMO1	0.024	-9999	-9999
HDAC4	0.011	-9999	-9999
Ran/GTP/Exportin 1/HDAC1	0	-9999	-9999
SUMO1	0.011	-9999	-9999
NPC/RanGAP1/SUMO1	0.013	-9999	-9999
mol:GTP	0	-9999	-9999
XPO1	0.022	-9999	-9999
EntrezGene:23636	0	-9999	-9999
RAN	0.011	-9999	-9999
EntrezGene:8021	0	-9999	-9999
RANBP2	0.011	-9999	-9999
SUMO1/HDAC4	0.024	-9999	-9999
SUMO1/HDAC1	0.024	-9999	-9999
RANGAP1	0.011	-9999	-9999
MDM2/SUMO1/SUMO1	0.027	-9999	-9999
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.017	-9999	-9999
Ran/GTP	0.021	-9999	-9999
EntrezGene:23225	0	-9999	-9999
MDM2	0.011	-9999	-9999
UBE2I	0.011	-9999	-9999
Ran/GTP/Exportin 1	0.026	-9999	-9999
NPC	0.006	-9999	-9999
PIAS2	0.011	-9999	-9999
PIAS1	0.011	-9999	-9999
EntrezGene:9972	0	-9999	-9999

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0	0	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.016	0.004	-9999	-10000	0	0
AP2	0.016	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0.015	0	-9999	-10000	0	0
CLTB	0.011	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.02	0	-9999	-10000	0	0
CD4	0.01	0.012	-9999	-0.27	1	1
CLTA	0.011	0	-9999	-10000	0	0
mol:GTP	0.001	0	-9999	-10000	0	0
ARFGAP1	0.009	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0.007	-9999	-0.15	1	1
ARF1/GTP	0	0.003	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.021	0	-9999	-10000	0	0
mol:Choline	0	0.007	-9999	-0.15	1	1
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.011	0	-9999	-10000	0	0
DDEF1	0	0.007	-9999	-0.16	1	1
ARF1/GDP	0	0.002	-9999	-10000	0	0
AP2M1	0.011	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0.013	0	-9999	-10000	0	0
Rac/GTP	0.009	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.02	0	-9999	-10000	0	0
ARFIP2	0.009	0	-9999	-10000	0	0
COPA	0.011	0	-9999	-10000	0	0
RAC1	0.011	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.02	0.002	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0.008	0	-9999	-10000	0	0
GGA3	0.011	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0.015	0.003	-9999	-10000	0	0
AP2A1	0.011	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.021	0	-9999	-10000	0	0
ARF1/GDP/Membrin	0.014	0.003	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0.014	0	-9999	-10000	0	0
CYTH2	0.011	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0.015	0	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0.008	0	-9999	-10000	0	0
mol:Brefeldin A	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.027	0.002	-9999	-10000	0	0
PLD2	0	0.007	-9999	-0.15	1	1
ARF-GAP1/v-SNARE	0.009	0	-9999	-10000	0	0
PIP5K1A	0	0.007	-9999	-0.15	1	1
ARF1/GTP/Membrin/GBF1/p115	0	0.003	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0.007	-9999	-0.15	1	1
KDEL Receptor/Ligand/ARF-GAP1	0.009	0	-9999	-10000	0	0
GOSR2	0	0	-9999	-10000	0	0
USO1	0	0	-9999	-10000	0	0
GBF1	0	0	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0.015	0.001	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.021	0.007	-9999	-10000	0	0

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.016	0	-9999	-10000	0	0
FBXW11	0.011	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.011	0	-9999	-10000	0	0
CHUK	0.011	0	-9999	-10000	0	0
NF kappa B2 p100/RelB	0.032	0	-9999	-10000	0	0
NFKB1	0.01	0.019	-9999	-0.42	1	1
MAP3K14	0.011	0	-9999	-10000	0	0
NF kappa B1 p50/RelB	0.015	0.013	-9999	-0.29	1	1
RELB	0.011	0	-9999	-10000	0	0
NFKB2	0.011	0	-9999	-10000	0	0
NF kappa B2 p52/RelB	0.014	0	-9999	-10000	0	0
regulation of B cell activation	0.014	0	-9999	-10000	0	0

pid_entity	TCGA.SL.A6JA	TCGA.SL.A6J9	TCGA.QS.A5YR	TCGA.QS.A5YQ
109_MAP3K5	0.042	0.042	0.042	-0.13
47_PPARGC1A	-0.42	-0.42	0.011	0.011
105_BMP4	0.011	-0.42	0.011	0.011
105_BMP6	0.011	0.011	0.011	0.011
105_BMP7	0.011	0.011	0.011	0.011
105_BMP2	0.011	-0.42	0.011	0.011
131_RELN/VLDLR	-0.2	-0.2	0.027	0.027
30_TGFB1/TGF beta receptor Type II	0.012	0.01	0.012	0.01
84_STAT5B	-0.025	-0.19	0.036	-0.022
84_STAT5A	-0.025	-0.19	0.036	-0.022