PARADIGM pathway analysis of mRNASeq expression and copy number data - Head and Neck Squamous Cell Carcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
IL4-mediated signaling events	108
HIF-1-alpha transcription factor network	99
Syndecan-1-mediated signaling events	95
Glypican 2 network	75
TCGA08_retinoblastoma	72
Syndecan-4-mediated signaling events	59
Syndecan-2-mediated signaling events	58
Endothelins	54
amb2 Integrin signaling	51
IL23-mediated signaling events	46

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
IL4-mediated signaling events	0.2077	108	9908	91	-1.2	0.99	1000	-1000	-0.18	-1000
HIF-1-alpha transcription factor network	0.1904	99	7572	76	-0.68	0.038	1000	-1000	-0.16	-1000
Syndecan-1-mediated signaling events	0.1827	95	3231	34	-0.32	0.028	1000	-1000	-0.052	-1000
Glypican 2 network	0.1442	75	300	4	-0.045	-0.027	1000	-1000	-0.001	-1000
TCGA08_retinoblastoma	0.1385	72	583	8	-0.13	0.083	1000	-1000	-0.005	-1000
Syndecan-4-mediated signaling events	0.1135	59	3959	67	-0.28	0.04	1000	-1000	-0.043	-1000
Syndecan-2-mediated signaling events	0.1115	58	4065	69	-0.2	0.037	1000	-1000	-0.038	-1000
Endothelins	0.1038	54	5247	96	-0.23	0.027	1000	-1000	-0.076	-1000
amb2 Integrin signaling	0.0981	51	4258	82	-0.26	0.035	1000	-1000	-0.047	-1000
IL23-mediated signaling events	0.0885	46	2811	60	-0.53	0.028	1000	-1000	-0.13	-1000
Signaling events regulated by Ret tyrosine kinase	0.0846	44	3614	82	-0.092	0.028	1000	-1000	-0.072	-1000
Nongenotropic Androgen signaling	0.0788	41	2157	52	-0.11	0.07	1000	-1000	-0.039	-1000
Effects of Botulinum toxin	0.0769	40	1064	26	-0.14	0.028	1000	-1000	-0.016	-1000
Coregulation of Androgen receptor activity	0.0750	39	2980	76	-0.43	0.067	1000	-1000	-0.025	-1000
TCGA08_p53	0.0750	39	274	7	-0.096	0.058	1000	-1000	-0.011	-1000
Calcium signaling in the CD4+ TCR pathway	0.0731	38	1208	31	-0.29	0.028	1000	-1000	-0.043	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0731	38	2964	78	-0.13	0.039	1000	-1000	-0.076	-1000
TCR signaling in naïve CD8+ T cells	0.0712	37	3448	93	-0.19	0.099	1000	-1000	-0.057	-1000
BMP receptor signaling	0.0692	36	2958	81	-0.22	0.048	1000	-1000	-0.064	-1000
Visual signal transduction: Rods	0.0692	36	1884	52	-0.21	0.041	1000	-1000	-0.048	-1000
p75(NTR)-mediated signaling	0.0673	35	4387	125	-0.24	0.075	1000	-1000	-0.075	-1000
Glypican 1 network	0.0673	35	1693	48	-0.28	0.046	1000	-1000	-0.042	-1000
Canonical Wnt signaling pathway	0.0635	33	1722	51	-0.2	0.14	1000	-1000	-0.059	-1000
Osteopontin-mediated events	0.0615	32	1223	38	-0.2	0.032	1000	-1000	-0.058	-1000
Reelin signaling pathway	0.0615	32	1813	56	-0.19	0.068	1000	-1000	-0.058	-1000
FOXA2 and FOXA3 transcription factor networks	0.0596	31	1428	46	-0.45	0.033	1000	-1000	-0.15	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0596	31	3794	120	-0.16	0.073	1000	-1000	-0.058	-1000
Fc-epsilon receptor I signaling in mast cells	0.0577	30	2953	97	-0.15	0.034	1000	-1000	-0.07	-1000
EGFR-dependent Endothelin signaling events	0.0577	30	638	21	-0.067	0.04	1000	-1000	-0.044	-1000
LPA4-mediated signaling events	0.0558	29	356	12	-0.087	0.007	1000	-1000	-0.029	-1000
Thromboxane A2 receptor signaling	0.0558	29	3047	105	-0.077	0.032	1000	-1000	-0.054	-1000
IGF1 pathway	0.0558	29	1670	57	-0.052	0.054	1000	-1000	-0.055	-1000
IL12-mediated signaling events	0.0519	27	2400	87	-0.16	0.037	1000	-1000	-0.12	-1000
Presenilin action in Notch and Wnt signaling	0.0519	27	1691	61	-0.2	0.075	1000	-1000	-0.063	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0519	27	1890	68	-0.31	0.04	1000	-1000	-0.1	-1000
Signaling mediated by p38-gamma and p38-delta	0.0500	26	395	15	-0.14	0.027	1000	-1000	-0.04	-1000
ErbB2/ErbB3 signaling events	0.0462	24	1594	65	-0.24	0.039	1000	-1000	-0.064	-1000
Arf6 signaling events	0.0462	24	1510	62	-0.11	0.053	1000	-1000	-0.051	-1000
Ephrin B reverse signaling	0.0462	24	1174	48	-0.083	0.034	1000	-1000	-0.036	-1000
LPA receptor mediated events	0.0462	24	2460	102	-0.26	0.027	1000	-1000	-0.061	-1000
Visual signal transduction: Cones	0.0442	23	887	38	-0.059	0.052	1000	-1000	-0.021	-1000
Integrins in angiogenesis	0.0442	23	1937	84	-0.2	0.054	1000	-1000	-0.052	-1000
Caspase cascade in apoptosis	0.0423	22	1657	74	-0.093	0.054	1000	-1000	-0.039	-1000
Signaling events mediated by the Hedgehog family	0.0423	22	1181	52	-0.21	0.03	1000	-1000	-0.054	-1000
Signaling events mediated by PTP1B	0.0423	22	1689	76	-0.086	0.045	1000	-1000	-0.051	-1000
IL1-mediated signaling events	0.0423	22	1378	62	-0.11	0.046	1000	-1000	-0.05	-1000
BCR signaling pathway	0.0423	22	2235	99	-0.062	0.047	1000	-1000	-0.065	-1000
Regulation of Androgen receptor activity	0.0423	22	1605	70	-0.46	0.034	1000	-1000	-0.058	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0404	21	1179	54	-0.13	0.038	1000	-1000	-0.062	-1000
Ephrin A reverse signaling	0.0404	21	149	7	-0.008	0.015	1000	-1000	-0.014	-1000
EPHB forward signaling	0.0404	21	1789	85	-0.17	0.092	1000	-1000	-0.077	-1000
Plasma membrane estrogen receptor signaling	0.0404	21	1833	86	-0.12	0.046	1000	-1000	-0.065	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0404	21	1868	88	-0.15	0.046	1000	-1000	-0.073	-1000
PDGFR-beta signaling pathway	0.0404	21	2081	97	-0.058	0.058	1000	-1000	-0.063	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0365	19	665	34	-0.026	0.032	1000	-1000	-0.04	-1000
Glucocorticoid receptor regulatory network	0.0365	19	2182	114	-0.34	0.17	1000	-1000	-0.066	-1000
Wnt signaling	0.0365	19	136	7	-0.019	0.023	1000	-1000	-0.037	-1000
Signaling events mediated by HDAC Class III	0.0346	18	736	40	-0.13	0.051	1000	-1000	-0.019	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0346	18	605	33	-0.13	0.063	1000	-1000	-0.046	-1000
ErbB4 signaling events	0.0327	17	1224	69	-0.24	0.04	1000	-1000	-0.057	-1000
Syndecan-3-mediated signaling events	0.0327	17	612	35	-0.15	0.075	1000	-1000	-0.036	-1000
IL27-mediated signaling events	0.0327	17	870	51	-0.12	0.054	1000	-1000	-0.06	-1000
Ceramide signaling pathway	0.0308	16	1253	76	-0.067	0.07	1000	-1000	-0.048	-1000
Signaling mediated by p38-alpha and p38-beta	0.0308	16	744	44	-0.13	0.028	1000	-1000	-0.036	-1000
PDGFR-alpha signaling pathway	0.0288	15	674	44	-0.11	0.06	1000	-1000	-0.048	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0288	15	825	52	-0.13	0.041	1000	-1000	-0.055	-1000
Regulation of nuclear SMAD2/3 signaling	0.0250	13	1840	136	-0.37	0.16	1000	-1000	-0.057	-1000
Noncanonical Wnt signaling pathway	0.0250	13	355	26	-0.052	0.027	1000	-1000	-0.062	-1000
S1P1 pathway	0.0250	13	488	36	-0.043	0.026	1000	-1000	-0.046	-1000
Cellular roles of Anthrax toxin	0.0231	12	483	39	-0.028	0.03	1000	-1000	-0.02	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0231	12	1072	85	-0.086	0.07	1000	-1000	-0.057	-1000
IFN-gamma pathway	0.0231	12	857	68	-0.13	0.041	1000	-1000	-0.067	-1000
FAS signaling pathway (CD95)	0.0231	12	572	47	-0.07	0.042	1000	-1000	-0.051	-1000
IL6-mediated signaling events	0.0231	12	909	75	-0.11	0.05	1000	-1000	-0.082	-1000
Signaling events mediated by PRL	0.0231	12	438	34	-0.066	0.04	1000	-1000	-0.048	-1000
p38 MAPK signaling pathway	0.0231	12	548	44	-0.11	0.056	1000	-1000	-0.033	-1000
BARD1 signaling events	0.0212	11	631	57	-0.034	0.052	1000	-1000	-0.06	-1000
mTOR signaling pathway	0.0212	11	608	53	-0.027	0.066	1000	-1000	-0.043	-1000
Nectin adhesion pathway	0.0212	11	732	63	-0.042	0.062	1000	-1000	-0.05	-1000
Retinoic acid receptors-mediated signaling	0.0212	11	690	58	-0.048	0.051	1000	-1000	-0.042	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0212	11	829	74	-0.27	0.058	1000	-1000	-0.076	-1000
S1P3 pathway	0.0212	11	486	42	-0.042	0.045	1000	-1000	-0.041	-1000
Rapid glucocorticoid signaling	0.0212	11	239	20	-0.03	0.035	1000	-1000	-0.007	-1000
EPO signaling pathway	0.0192	10	575	55	-0.014	0.05	1000	-1000	-0.054	-1000
PLK1 signaling events	0.0192	10	881	85	-0.042	0.067	1000	-1000	-0.037	-1000
Class I PI3K signaling events mediated by Akt	0.0192	10	699	68	-0.096	0.062	1000	-1000	-0.045	-1000
ceramide signaling pathway	0.0192	10	523	49	0	0.064	1000	-1000	-0.049	-1000
IL2 signaling events mediated by PI3K	0.0192	10	606	58	-0.078	0.081	1000	-1000	-0.058	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0192	10	460	45	-0.022	0.052	1000	-1000	-0.056	-1000
Regulation of p38-alpha and p38-beta	0.0173	9	491	54	-0.035	0.061	1000	-1000	-0.057	-1000
Ras signaling in the CD4+ TCR pathway	0.0173	9	168	17	-0.001	0.044	1000	-1000	-0.032	-1000
Circadian rhythm pathway	0.0154	8	193	22	-0.054	0.056	1000	-1000	-0.046	-1000
JNK signaling in the CD4+ TCR pathway	0.0154	8	149	17	0.01	0.052	1000	-1000	-0.041	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0154	8	331	37	-0.021	0.063	1000	-1000	-0.041	-1000
Regulation of Telomerase	0.0154	8	894	102	-0.07	0.06	1000	-1000	-0.069	-1000
FOXM1 transcription factor network	0.0154	8	420	51	-0.13	0.14	1000	-1000	-0.18	-1000
Aurora B signaling	0.0154	8	589	67	-0.31	0.088	1000	-1000	-0.055	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0135	7	198	28	-0.041	0.051	1000	-1000	-0.028	-1000
TCGA08_rtk_signaling	0.0135	7	200	26	-0.067	0.088	1000	-1000	-0.027	-1000
VEGFR1 specific signals	0.0135	7	398	56	-0.041	0.051	1000	-1000	-0.054	-1000
HIF-2-alpha transcription factor network	0.0115	6	271	43	-0.098	0.045	1000	-1000	-0.076	-1000
IL2 signaling events mediated by STAT5	0.0115	6	147	22	-0.016	0.043	1000	-1000	-0.057	-1000
Arf6 trafficking events	0.0115	6	433	71	-0.18	0.049	1000	-1000	-0.035	-1000
Insulin Pathway	0.0115	6	500	74	-0.084	0.072	1000	-1000	-0.055	-1000
Class IB PI3K non-lipid kinase events	0.0115	6	18	3	-0.022	0.022	1000	-1000	-0.002	-1000
a4b1 and a4b7 Integrin signaling	0.0096	5	28	5	0.021	0.034	1000	-1000	0	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0096	5	425	83	-0.031	0.054	1000	-1000	-0.049	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0096	5	709	125	-0.037	0.072	1000	-1000	-0.061	-1000
E-cadherin signaling in the nascent adherens junction	0.0096	5	391	76	-0.021	0.068	1000	-1000	-0.065	-1000
Class I PI3K signaling events	0.0096	5	399	73	-0.035	0.049	1000	-1000	-0.06	-1000
E-cadherin signaling in keratinocytes	0.0096	5	254	43	-0.041	0.062	1000	-1000	-0.042	-1000
S1P4 pathway	0.0096	5	143	25	0	0.037	1000	-1000	-0.035	-1000
Hedgehog signaling events mediated by Gli proteins	0.0077	4	269	65	-0.023	0.065	1000	-1000	-0.06	-1000
Aurora A signaling	0.0077	4	246	60	-0.04	0.056	1000	-1000	-0.028	-1000
Aurora C signaling	0.0077	4	28	7	0	0.042	1000	-1000	-0.02	-1000
TRAIL signaling pathway	0.0077	4	219	48	0	0.07	1000	-1000	-0.044	-1000
FoxO family signaling	0.0077	4	261	64	-0.016	0.086	1000	-1000	-0.087	-1000
E-cadherin signaling events	0.0077	4	20	5	0.021	0.043	1000	-1000	-0.002	-1000
Canonical NF-kappaB pathway	0.0058	3	133	39	0	0.06	1000	-1000	-0.056	-1000
Arf6 downstream pathway	0.0058	3	133	43	-0.041	0.042	1000	-1000	-0.033	-1000
Insulin-mediated glucose transport	0.0058	3	98	32	-0.07	0.053	1000	-1000	-0.042	-1000
S1P5 pathway	0.0058	3	52	17	-0.023	0.032	1000	-1000	-0.027	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0038	2	61	23	0.003	0.049	1000	-1000	-0.033	-1000
Paxillin-dependent events mediated by a4b1	0.0038	2	107	36	-0.052	0.054	1000	-1000	-0.052	-1000
Atypical NF-kappaB pathway	0.0038	2	69	31	0	0.033	1000	-1000	-0.033	-1000
Signaling events mediated by HDAC Class II	0.0019	1	143	75	-0.033	0.067	1000	-1000	-0.032	-1000
PLK2 and PLK4 events	0.0019	1	4	3	0.013	0.027	1000	-1000	-0.02	-1000
Signaling events mediated by HDAC Class I	0.0019	1	177	104	-0.074	0.067	1000	-1000	-0.048	-1000
Alternative NF-kappaB pathway	0.0019	1	16	13	0	0.074	1000	-1000	-0.001	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	10	27	0	0.061	1000	-1000	-0.04	-1000
Arf1 pathway	0.0000	0	40	54	-0.001	0.038	1000	-1000	-0.026	-1000
Total	NA	2652	159673	7203	-16	7.8	131000	-131000	-6.8	-131000

IL4-mediated signaling events

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
BCL2L1	-0.87	0.46	-10000	0	-1.3	243	243
STAT6 (cleaved dimer)	-0.88	0.48	-10000	0	-1.2	283	283
IGHG1	-0.31	0.16	-10000	0	-0.51	76	76
IGHG3	-0.85	0.44	-10000	0	-1.2	280	280
AKT1	-0.37	0.2	-10000	0	-0.82	37	37
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.26	0.17	-10000	0	-0.77	21	21
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.38	0.2	-10000	0	-0.86	32	32
THY1	-0.91	0.48	-10000	0	-1.3	272	272
MYB	-0.018	0.14	-10000	0	-0.45	48	48
HMGA1	0.027	0.006	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.45	0.21	-10000	0	-0.76	61	61
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.38	0.21	-10000	0	-0.86	32	32
SP1	0.003	0.04	-10000	0	-10000	0	0
INPP5D	0.025	0.031	-10000	0	-0.46	2	2
SOCS5	0.048	0.014	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.87	0.47	-10000	0	-1.2	271	271
SOCS1	-0.57	0.26	-10000	0	-0.8	202	202
SOCS3	-0.38	0.18	-10000	0	-0.79	18	18
FCER2	-0.69	0.36	-10000	0	-1	187	187
PARP14	0.024	0.021	-10000	0	-0.39	1	1
CCL17	-0.9	0.47	-10000	0	-1.3	243	243
GRB2	0.027	0.004	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.31	0.17	-10000	0	-0.73	30	30
T cell proliferation	-0.88	0.48	-10000	0	-1.3	254	254
IL4R/JAK1	-0.88	0.46	-10000	0	-1.3	255	255
EGR2	-0.89	0.47	-10000	0	-1.3	231	231
JAK2	-0.048	0.03	-10000	0	-10000	0	0
JAK3	0.016	0.086	-10000	0	-0.39	22	22
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
JAK1	-0.011	0.017	-10000	0	-10000	0	0
COL1A2	-0.34	0.2	-10000	0	-0.76	13	13
CCL26	-0.9	0.47	-10000	0	-1.3	253	253
IL4R	-0.93	0.5	-10000	0	-1.4	253	253
PTPN6	0.045	0.014	-10000	0	-10000	0	0
IL13RA2	-0.9	0.47	-10000	0	-1.3	256	256
IL13RA1	-0.052	0.028	-10000	0	-10000	0	0
IRF4	-0.25	0.32	-10000	0	-0.92	75	75
ARG1	-0.55	0.57	-10000	0	-1.5	139	139
CBL	-0.43	0.2	-10000	0	-0.72	56	56
GTF3A	-0.017	0.04	-10000	0	-10000	0	0
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.06	0.041	-10000	0	-10000	0	0
IRF4/BCL6	-0.2	0.29	-10000	0	-0.84	67	67
CD40LG	-0.034	0.16	-10000	0	-0.46	64	64
MAPK14	-0.42	0.2	-10000	0	-0.75	47	47
mitosis	-0.35	0.19	-10000	0	-0.76	37	37
STAT6	-1	0.58	-10000	0	-1.5	275	275
SPI1	-0.019	0.075	-10000	0	-0.43	3	3
RPS6KB1	-0.34	0.18	-10000	0	-0.74	34	34
STAT6 (dimer)	-1	0.58	-10000	0	-1.5	274	274
STAT6 (dimer)/PARP14	-0.93	0.53	-10000	0	-1.3	266	266
mast cell activation	0.02	0.007	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.36	0.21	-10000	0	-0.87	37	37
FRAP1	-0.37	0.2	-10000	0	-0.82	37	37
LTA	-0.89	0.46	-10000	0	-1.3	256	256
FES	0.027	0.004	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0.99	0.54	1.4	275	-10000	0	275
CCL11	-0.92	0.44	-10000	0	-1.2	288	288
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.35	0.19	-10000	0	-0.8	30	30
IL2RG	0.02	0.078	-10000	0	-0.4	17	17
IL10	-0.88	0.46	-10000	0	-1.3	249	249
IRS1	0.024	0.038	-10000	0	-0.46	3	3
IRS2	0.025	0.031	-10000	0	-0.46	2	2
IL4	-0.23	0.24	-10000	0	-1.1	30	30
IL5	-0.88	0.46	-10000	0	-1.3	247	247
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.69	0.34	-10000	0	-0.96	240	240
COL1A1	-0.45	0.25	-10000	0	-0.74	106	106
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.9	0.49	-10000	0	-1.3	243	243
IL2R gamma/JAK3	0.018	0.092	-10000	0	-0.31	35	35
TFF3	-1.1	0.6	-10000	0	-1.6	291	291
ALOX15	-0.96	0.52	-10000	0	-1.4	275	275
MYBL1	0.021	0.041	-10000	0	-0.39	5	5
T-helper 2 cell differentiation	-0.78	0.39	-10000	0	-1.1	269	269
SHC1	0.028	0.004	-10000	0	-10000	0	0
CEBPB	-0.014	0.066	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.36	0.19	-10000	0	-0.82	26	26
mol:PI-3-4-5-P3	-0.37	0.2	-10000	0	-0.82	37	37
PI3K	-0.38	0.22	-10000	0	-0.88	37	37
DOK2	0.022	0.039	-10000	0	-0.41	4	4
ETS1	0.041	0.036	-10000	0	-0.38	3	3
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.29	0.16	-10000	0	-0.66	25	25
ITGB3	-0.89	0.47	-10000	0	-1.3	252	252
PIGR	-1.2	0.62	-10000	0	-1.6	358	358
IGHE	0.045	0.054	0.2	13	-0.17	1	14
MAPKKK cascade	-0.29	0.15	-10000	0	-0.64	25	25
BCL6	0.02	0.013	-10000	0	-10000	0	0
OPRM1	-0.88	0.46	-10000	0	-1.3	249	249
RETNLB	-0.87	0.47	-10000	0	-1.3	227	227
SELP	-0.95	0.53	-10000	0	-1.4	257	257
AICDA	-0.85	0.44	-10000	0	-1.2	244	244

×

HIF-1-alpha 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.57	0.38	-10000	0	-0.98	177	177
HDAC7	0.028	0.004	-10000	0	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.42	0.28	-10000	0	-0.81	80	80
SMAD4	0.026	0.009	-10000	0	-10000	0	0
ID2	-0.57	0.38	-10000	0	-1	146	146
AP1	-0.006	0.12	-10000	0	-0.33	63	63
ABCG2	-0.57	0.39	-10000	0	-1	150	150
HIF1A	-0.09	0.066	-10000	0	-0.6	1	1
TFF3	-0.66	0.44	-10000	0	-1.1	208	208
GATA2	0.023	0.03	-10000	0	-0.42	2	2
AKT1	-0.092	0.068	-10000	0	-0.41	2	2
response to hypoxia	-0.1	0.076	-10000	0	-0.34	20	20
MCL1	-0.56	0.38	-10000	0	-1	147	147
NDRG1	-0.54	0.38	-10000	0	-1	135	135
SERPINE1	-0.64	0.41	-10000	0	-1	201	201
FECH	-0.56	0.38	-10000	0	-1	148	148
FURIN	-0.56	0.38	-10000	0	-1	149	149
NCOA2	-0.011	0.12	-10000	0	-0.46	36	36
EP300	-0.089	0.082	-10000	0	-0.37	11	11
HMOX1	-0.57	0.38	-10000	0	-1	141	141
BHLHE40	-0.56	0.38	-10000	0	-1	147	147
BHLHE41	-0.56	0.39	-10000	0	-1	148	148
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.083	0.092	-10000	0	-0.38	2	2
ENG	-0.079	0.084	0.33	5	-0.38	1	6
JUN	0.028	0.006	-10000	0	-10000	0	0
RORA	-0.57	0.39	-10000	0	-1	148	148
ABCB1	-0.18	0.3	-10000	0	-1.2	36	36
TFRC	-0.53	0.38	-10000	0	-1	136	136
CXCR4	-0.57	0.39	-10000	0	-1	155	155
TF	-0.68	0.44	-10000	0	-1.1	227	227
CITED2	-0.56	0.38	-10000	0	-1	148	148
HIF1A/ARNT	-0.62	0.45	-10000	0	-1.2	149	149
LDHA	-0.081	0.16	-10000	0	-0.8	21	21
ETS1	-0.56	0.38	-10000	0	-1	148	148
PGK1	-0.56	0.38	-10000	0	-1	149	149
NOS2	-0.59	0.39	-10000	0	-1	163	163
ITGB2	-0.57	0.38	-10000	0	-1	154	154
ALDOA	-0.56	0.38	-10000	0	-1	147	147
Cbp/p300/CITED2	-0.56	0.39	-10000	0	-1	134	134
FOS	-0.033	0.16	-10000	0	-0.46	63	63
HK2	-0.56	0.38	-10000	0	-1	148	148
SP1	0.027	0.029	-10000	0	-10000	0	0
GCK	-0.15	0.14	-10000	0	-0.71	9	9
HK1	-0.56	0.38	-10000	0	-1	149	149
NPM1	-0.56	0.38	-10000	0	-1	146	146
EGLN1	-0.56	0.38	-10000	0	-1	147	147
CREB1	0.033	0.006	-10000	0	-10000	0	0
PGM1	-0.56	0.38	-10000	0	-1	148	148
SMAD3	0.028	0.005	-10000	0	-10000	0	0
EDN1	-0.089	0.16	-10000	0	-1	8	8
IGFBP1	-0.57	0.38	-10000	0	-1	147	147
VEGFA	-0.37	0.25	-10000	0	-0.73	61	61
HIF1A/JAB1	-0.049	0.049	-10000	0	-10000	0	0
CP	-0.61	0.43	-10000	0	-1	196	196
CXCL12	-0.58	0.4	-10000	0	-1	158	158
COPS5	0.024	0.012	-10000	0	-10000	0	0
SMAD3/SMAD4	0.038	0.014	-10000	0	-10000	0	0
BNIP3	-0.56	0.38	-10000	0	-1	147	147
EGLN3	-0.57	0.39	-10000	0	-1	155	155
CA9	-0.68	0.4	-10000	0	-1	231	231
TERT	-0.58	0.4	-10000	0	-1	171	171
ENO1	-0.56	0.38	-10000	0	-1	146	146
PFKL	-0.56	0.38	-10000	0	-1	147	147
NCOA1	0.027	0.005	-10000	0	-10000	0	0
ADM	-0.57	0.39	-10000	0	-1	149	149
ARNT	-0.098	0.069	-10000	0	-0.35	9	9
HNF4A	-0.019	0.12	-10000	0	-0.39	49	49
ADFP	-0.57	0.38	-10000	0	-0.98	177	177
SLC2A1	-0.37	0.25	-10000	0	-0.75	57	57
LEP	-0.59	0.4	-10000	0	-1	171	171
HIF1A/ARNT/Cbp/p300	-0.43	0.29	-10000	0	-0.82	87	87
EPO	-0.34	0.25	-10000	0	-0.81	58	58
CREBBP	-0.089	0.081	-10000	0	-0.38	9	9
HIF1A/ARNT/Cbp/p300/HDAC7	-0.41	0.29	-10000	0	-0.82	77	77
PFKFB3	-0.56	0.38	-10000	0	-1	147	147
NT5E	-0.59	0.4	-10000	0	-1	170	170

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.025	0.032	-10000	0	-0.39	3	3
CCL5	-0.034	0.15	-10000	0	-0.39	76	76
SDCBP	0.025	0.009	-10000	0	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.18	0.14	0.27	10	-0.33	155	165
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
Syndecan-1/Laminin-5	-0.18	0.13	0.2	6	-0.32	153	159
Syndecan-1/Syntenin	-0.17	0.13	0.32	3	-0.32	140	143
MAPK3	-0.16	0.12	0.24	9	-0.4	36	45
HGF/MET	0.02	0.079	-10000	0	-0.31	28	28
TGFB1/TGF beta receptor Type II	0.025	0.032	-10000	0	-0.39	3	3
BSG	0.027	0.005	-10000	0	-10000	0	0
keratinocyte migration	-0.18	0.13	0.2	6	-0.31	153	159
Syndecan-1/RANTES	-0.2	0.15	0.32	4	-0.34	200	204
Syndecan-1/CD147	-0.17	0.13	0.31	4	-0.42	37	41
Syndecan-1/Syntenin/PIP2	-0.16	0.13	0.3	3	-0.31	140	143
LAMA5	0.027	0.006	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	-0.16	0.12	0.29	3	-0.3	140	143
MMP7	-0.11	0.19	-10000	0	-0.39	160	160
HGF	0.006	0.095	-10000	0	-0.44	22	22
Syndecan-1/CASK	-0.18	0.12	-10000	0	-0.32	157	157
Syndecan-1/HGF/MET	-0.18	0.13	0.31	3	-0.4	51	54
regulation of cell adhesion	-0.16	0.12	0.28	4	-0.39	33	37
HPSE	0.023	0.043	-10000	0	-0.46	4	4
positive regulation of cell migration	-0.18	0.14	0.27	10	-0.33	155	165
SDC1	-0.19	0.13	0.22	1	-0.33	153	154
Syndecan-1/Collagen	-0.18	0.14	0.27	10	-0.33	155	165
PPIB	0.028	0.004	-10000	0	-10000	0	0
MET	0.022	0.048	-10000	0	-0.41	6	6
PRKACA	0.028	0.004	-10000	0	-10000	0	0
MMP9	-0.26	0.19	-10000	0	-0.39	355	355
MAPK1	-0.16	0.12	0.23	10	-0.39	36	46
homophilic cell adhesion	-0.18	0.14	0.27	10	-0.33	157	167
MMP1	-0.32	0.15	-10000	0	-0.39	427	427

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	0.009	0.085	-9999	-0.39	22	22
GPC2	-0.045	0.16	-9999	-0.39	88	88
GPC2/Midkine	-0.027	0.14	-9999	-0.3	95	95
neuron projection morphogenesis	-0.027	0.14	-9999	-0.3	95	95

×

TCGA08_retinoblastoma

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
CDKN2B	0.01	0.07	-10000	0	-0.43	12	12
CDKN2C	0.016	0.077	-10000	0	-0.35	19	19
CDKN2A	-0.13	0.19	-10000	0	-0.39	187	187
CCND2	0.04	0.063	0.18	51	-10000	0	51
RB1	-0.079	0.098	0.3	1	-0.23	113	114
CDK4	0.047	0.073	0.22	44	-10000	0	44
CDK6	0.044	0.07	0.22	38	-10000	0	38
G1/S progression	0.083	0.098	0.23	117	-0.3	1	118

×

Syndecan-4-mediated signaling events

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
PTK2	-0.097	0.16	-10000	0	-0.55	33	33
Syndecan-4/Syndesmos	-0.16	0.15	-10000	0	-0.49	38	38
positive regulation of JNK cascade	-0.17	0.15	-10000	0	-0.48	42	42
Syndecan-4/ADAM12	-0.28	0.18	-10000	0	-0.44	221	221
CCL5	-0.034	0.15	-10000	0	-0.39	76	76
Rac1/GDP	0.019	0.005	-10000	0	-10000	0	0
DNM2	0.028	0.004	-10000	0	-10000	0	0
ITGA5	-0.1	0.19	-10000	0	-0.39	161	161
SDCBP	0.025	0.009	-10000	0	-10000	0	0
PLG	0.014	0.045	-10000	0	-0.38	5	5
ADAM12	-0.27	0.19	-10000	0	-0.39	370	370
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0.027	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.078	0.043	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	-0.22	0.18	-10000	0	-0.44	136	136
Syndecan-4/CXCL12/CXCR4	-0.17	0.16	-10000	0	-0.51	42	42
Syndecan-4/Laminin alpha3	-0.2	0.17	-10000	0	-0.44	105	105
MDK	0.009	0.085	-10000	0	-0.39	22	22
Syndecan-4/FZD7	-0.16	0.16	-10000	0	-0.48	41	41
Syndecan-4/Midkine	-0.16	0.16	-10000	0	-0.48	42	42
FZD7	0.022	0.046	-10000	0	-0.4	6	6
Syndecan-4/FGFR1/FGF	-0.14	0.15	-10000	0	-0.58	18	18
THBS1	0.014	0.076	-10000	0	-0.41	16	16
integrin-mediated signaling pathway	-0.18	0.16	-10000	0	-0.43	91	91
positive regulation of MAPKKK cascade	-0.17	0.15	-10000	0	-0.48	42	42
Syndecan-4/TACI	-0.17	0.16	-10000	0	-0.46	54	54
CXCR4	0.013	0.076	-10000	0	-0.39	18	18
cell adhesion	-0.069	0.098	0.2	5	-0.21	113	118
Syndecan-4/Dynamin	-0.15	0.15	-10000	0	-0.49	38	38
Syndecan-4/TSP1	-0.16	0.16	-10000	0	-0.47	48	48
Syndecan-4/GIPC	-0.15	0.15	-10000	0	-0.49	37	37
Syndecan-4/RANTES	-0.18	0.16	-10000	0	-0.45	70	70
ITGB1	0.027	0.005	-10000	0	-10000	0	0
LAMA1	-0.14	0.2	-10000	0	-0.39	207	207
LAMA3	-0.083	0.18	-10000	0	-0.39	135	135
RAC1	0.026	0.007	-10000	0	-10000	0	0
PRKCA	0.04	0.098	0.86	6	-0.4	2	8
Syndecan-4/alpha-Actinin	-0.15	0.15	-10000	0	-0.49	38	38
TFPI	0.023	0.044	-10000	0	-0.42	5	5
F2	-0.035	0.12	-10000	0	-0.39	52	52
alpha5/beta1 Integrin	-0.058	0.14	-10000	0	-0.27	161	161
positive regulation of cell adhesion	-0.25	0.19	-10000	0	-0.47	172	172
ACTN1	0.027	0.006	-10000	0	-10000	0	0
TNC	-0.049	0.16	-10000	0	-0.39	94	94
Syndecan-4/CXCL12	-0.17	0.16	-10000	0	-0.5	47	47
FGF6	-0.009	0.018	-10000	0	-10000	0	0
RHOA	0.025	0.009	-10000	0	-10000	0	0
CXCL12	-0.021	0.15	-10000	0	-0.46	51	51
TNFRSF13B	-0.022	0.12	-10000	0	-0.39	53	53
FGF2	0.011	0.085	-10000	0	-0.44	17	17
FGFR1	0.019	0.047	-10000	0	-0.4	6	6
Syndecan-4/PI-4-5-P2	-0.16	0.14	-10000	0	-0.48	39	39
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	-0.15	0.2	-10000	0	-0.38	222	222
cell migration	-0.031	0.017	-10000	0	-10000	0	0
PRKCD	0.029	0.015	-10000	0	-10000	0	0
vasculogenesis	-0.16	0.15	-10000	0	-0.45	48	48
SDC4	-0.16	0.15	-10000	0	-0.5	38	38
Syndecan-4/Tenascin C	-0.18	0.17	-10000	0	-0.45	91	91
Syndecan-4/PI-4-5-P2/PKC alpha	-0.062	0.034	-10000	0	-10000	0	0
Syndecan-4/Syntenin	-0.15	0.15	-10000	0	-0.5	34	34
MMP9	-0.26	0.19	-10000	0	-0.38	355	355
Rac1/GTP	-0.07	0.1	0.21	5	-0.22	113	118
cytoskeleton organization	-0.15	0.15	-10000	0	-0.46	38	38
GIPC1	0.028	0.004	-10000	0	-10000	0	0
Syndecan-4/TFPI	-0.15	0.16	-10000	0	-0.48	40	40

×

Syndecan-2-mediated signaling events

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
Syndecan-2/Fibronectin	-0.076	0.13	-10000	0	-0.24	197	197
EPHB2	-0.084	0.18	-10000	0	-0.39	137	137
Syndecan-2/TACI	-0.008	0.086	-10000	0	-0.22	68	68
LAMA1	-0.14	0.2	-10000	0	-0.39	207	207
Syndecan-2/alpha2 ITGB1	-0.013	0.11	-10000	0	-0.36	7	7
HRAS	0.026	0.02	-10000	0	-0.4	1	1
Syndecan-2/CASK	0	0.044	-10000	0	-0.22	20	20
ITGA5	-0.1	0.19	-10000	0	-0.39	161	161
BAX	0	0.046	-10000	0	-0.42	1	1
EPB41	0.027	0.004	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	0.016	0.043	-10000	0	-0.2	19	19
LAMA3	-0.083	0.18	-10000	0	-0.39	135	135
EZR	0.027	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	0.025	0.031	-10000	0	-0.46	2	2
Syndecan-2/MMP2	-0.012	0.1	-10000	0	-0.26	67	67
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.037	0.026	-10000	0	-0.33	2	2
dendrite morphogenesis	-0.038	0.11	-10000	0	-0.23	127	127
Syndecan-2/GM-CSF	-0.1	0.13	-10000	0	-0.23	248	248
determination of left/right symmetry	0.001	0.053	-10000	0	-0.26	20	20
Syndecan-2/PKC delta	0.014	0.049	-10000	0	-0.22	20	20
GNB2L1	0.026	0.007	-10000	0	-10000	0	0
MAPK3	-0.084	0.13	0.19	27	-0.21	242	269
MAPK1	-0.081	0.13	0.19	26	-0.21	237	263
Syndecan-2/RACK1	0.027	0.048	-10000	0	-0.19	20	20
NF1	0.027	0.004	-10000	0	-10000	0	0
FGFR/FGF/Syndecan-2	0.001	0.053	-10000	0	-0.26	20	20
ITGA2	0.024	0.038	-10000	0	-0.46	3	3
MAPK8	0.002	0.049	-10000	0	-0.23	21	21
Syndecan-2/alpha2/beta1 Integrin	-0.046	0.12	-10000	0	-0.36	13	13
Syndecan-2/Kininogen	0.005	0.056	-10000	0	-0.24	23	23
ITGB1	0.027	0.005	-10000	0	-10000	0	0
SRC	0.027	0.067	0.19	45	-10000	0	45
Syndecan-2/CASK/Protein 4.1	0.016	0.044	-10000	0	-0.2	20	20
extracellular matrix organization	0.016	0.053	-10000	0	-0.23	21	21
actin cytoskeleton reorganization	-0.076	0.13	-10000	0	-0.24	197	197
Syndecan-2/Caveolin-2/Ras	0.028	0.054	-10000	0	-0.22	20	20
Syndecan-2/Laminin alpha3	-0.039	0.11	-10000	0	-0.23	129	129
Syndecan-2/RasGAP	0.037	0.054	-10000	0	-0.4	1	1
alpha5/beta1 Integrin	-0.058	0.14	-10000	0	-0.27	161	161
PRKCD	0.024	0.009	-10000	0	-10000	0	0
Syndecan-2 dimer	-0.038	0.12	-10000	0	-0.23	127	127
GO:0007205	0.003	0	-10000	0	-10000	0	0
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	0.026	0.05	-10000	0	-0.39	1	1
RHOA	0.025	0.009	-10000	0	-10000	0	0
SDCBP	0.025	0.009	-10000	0	-10000	0	0
TNFRSF13B	-0.022	0.12	-10000	0	-0.39	53	53
RASA1	0.024	0.031	-10000	0	-0.46	2	2
alpha2/beta1 Integrin	0.037	0.026	-10000	0	-0.33	2	2
Syndecan-2/Synbindin	0.015	0.049	-10000	0	-0.22	20	20
TGFB1	0.025	0.032	-10000	0	-0.39	3	3
CASP3	0.024	0.069	0.19	50	-0.2	16	66
FN1	-0.15	0.2	-10000	0	-0.39	222	222
Syndecan-2/IL8	-0.03	0.11	-10000	0	-0.23	109	109
SDC2	0.001	0.053	-10000	0	-0.26	20	20
KNG1	-0.013	0.067	-10000	0	-0.39	15	15
Syndecan-2/Neurofibromin	0.017	0.049	-10000	0	-0.22	20	20
TRAPPC4	0.025	0.008	-10000	0	-10000	0	0
CSF2	-0.2	0.21	-10000	0	-0.39	276	276
Syndecan-2/TGFB1	0.016	0.053	-10000	0	-0.23	21	21
Syndecan-2/Syntenin/PI-4-5-P2	0.016	0.043	-10000	0	-0.2	19	19
Syndecan-2/Ezrin	0.027	0.049	-10000	0	-10000	0	0
PRKACA	0.029	0.073	0.19	60	-0.2	19	79
angiogenesis	-0.029	0.11	-10000	0	-0.23	109	109
MMP2	-0.024	0.14	-10000	0	-0.39	62	62
IL8	-0.059	0.17	-10000	0	-0.39	106	106
calcineurin-NFAT signaling pathway	-0.008	0.085	-10000	0	-0.22	68	68

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.11	0.19	0.25	2	-0.43	62	64
PTK2B	0.026	0.008	-10000	0	-10000	0	0
mol:Ca2+	-0.042	0.17	-10000	0	-0.59	14	14
EDN1	-0.069	0.15	-10000	0	-0.3	59	59
EDN3	-0.18	0.22	-10000	0	-0.46	197	197
EDN2	-0.04	0.16	-10000	0	-0.44	75	75
HRAS/GDP	-0.063	0.16	0.31	4	-0.43	34	38
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.055	0.13	-10000	0	-0.36	46	46
ADCY4	-0.11	0.16	0.27	5	-0.38	80	85
ADCY5	-0.16	0.18	0.24	2	-0.41	119	121
ADCY6	-0.12	0.17	0.28	4	-0.39	86	90
ADCY7	-0.12	0.17	0.27	5	-0.39	81	86
ADCY1	-0.12	0.17	0.26	6	-0.4	81	87
ADCY2	-0.18	0.18	0.26	2	-0.42	137	139
ADCY3	-0.12	0.17	0.27	5	-0.38	82	87
ADCY8	-0.11	0.16	0.32	2	-0.39	75	77
ADCY9	-0.12	0.17	0.27	5	-0.38	81	86
arachidonic acid secretion	-0.089	0.19	0.27	3	-0.48	63	66
ETB receptor/Endothelin-1/Gq/GTP	-0.051	0.12	-10000	0	-0.36	36	36
GNAO1	0.023	0.039	-10000	0	-0.41	4	4
HRAS	0.026	0.02	-10000	0	-0.4	1	1
ETA receptor/Endothelin-1/G12/GTP	-0.037	0.22	0.33	8	-0.4	60	68
ETA receptor/Endothelin-1/Gs/GTP	-0.072	0.22	0.32	5	-0.4	86	91
mol:GTP	0	0.004	-10000	0	-10000	0	0
COL3A1	-0.21	0.26	-10000	0	-0.48	200	200
EDNRB	-0.009	0.062	-10000	0	-0.46	4	4
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.13	0.22	-10000	0	-0.51	74	74
CYSLTR1	-0.15	0.25	-10000	0	-0.55	100	100
SLC9A1	-0.047	0.11	-10000	0	-0.25	55	55
mol:GDP	-0.072	0.16	0.31	4	-0.44	40	44
SLC9A3	-0.15	0.3	-10000	0	-0.65	110	110
RAF1	-0.093	0.18	0.27	5	-0.46	60	65
JUN	-0.048	0.17	-10000	0	-0.67	10	10
JAK2	-0.11	0.18	0.26	4	-0.43	61	65
mol:IP3	-0.067	0.14	-10000	0	-0.4	45	45
ETA receptor/Endothelin-1	-0.071	0.28	0.39	7	-0.48	76	83
PLCB1	0.025	0.023	-10000	0	-0.46	1	1
PLCB2	0.023	0.039	-10000	0	-0.41	4	4
ETA receptor/Endothelin-3	-0.16	0.19	-10000	0	-0.38	200	200
FOS	-0.14	0.32	0.31	1	-0.9	69	70
Gai/GDP	-0.073	0.26	-10000	0	-0.71	71	71
CRK	0.027	0.006	-10000	0	-10000	0	0
mol:Ca ++	-0.13	0.19	0.24	1	-0.47	57	58
BCAR1	0.027	0.006	-10000	0	-10000	0	0
PRKCB1	-0.066	0.14	0.25	2	-0.38	49	51
GNAQ	0.027	0.009	-10000	0	-10000	0	0
GNAZ	0.012	0.079	-10000	0	-0.41	17	17
GNAL	-0.03	0.16	-10000	0	-0.46	59	59
Gs family/GDP	-0.084	0.16	0.25	1	-0.45	42	43
ETA receptor/Endothelin-1/Gq/GTP	-0.065	0.15	-10000	0	-0.37	55	55
MAPK14	-0.038	0.11	0.24	1	-0.44	14	15
TRPC6	-0.044	0.18	-10000	0	-0.62	14	14
GNAI2	0.024	0.009	-10000	0	-10000	0	0
GNAI3	0.027	0.005	-10000	0	-10000	0	0
GNAI1	0.026	0.022	-10000	0	-0.46	1	1
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.042	0.12	-10000	0	-0.41	23	23
ETB receptor/Endothelin-2	-0.041	0.12	-10000	0	-0.32	79	79
ETB receptor/Endothelin-3	-0.13	0.17	-10000	0	-0.34	195	195
ETB receptor/Endothelin-1	-0.049	0.14	-10000	0	-0.27	61	61
MAPK3	-0.13	0.28	0.3	2	-0.76	71	73
MAPK1	-0.13	0.28	0.3	2	-0.76	71	73
Rac1/GDP	-0.063	0.15	0.32	3	-0.43	32	35
cAMP biosynthetic process	-0.14	0.16	0.28	6	-0.44	65	71
MAPK8	-0.057	0.19	0.34	1	-0.61	28	29
SRC	0.026	0.007	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.019	0.087	-10000	0	-0.36	15	15
p130Cas/CRK/Src/PYK2	-0.069	0.16	0.3	6	-0.5	26	32
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.063	0.15	0.32	3	-0.43	33	36
COL1A2	-0.15	0.24	-10000	0	-0.45	163	163
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.079	0.16	-10000	0	-0.36	79	79
mol:DAG	-0.067	0.14	-10000	0	-0.4	45	45
MAP2K2	-0.11	0.22	0.3	3	-0.56	74	77
MAP2K1	-0.11	0.22	0.3	2	-0.57	72	74
EDNRA	-0.063	0.14	-10000	0	-0.32	30	30
positive regulation of muscle contraction	-0.084	0.16	0.28	8	-0.39	54	62
Gq family/GDP	-0.051	0.17	-10000	0	-0.44	35	35
HRAS/GTP	-0.082	0.16	0.28	4	-0.43	47	51
PRKCH	-0.059	0.14	0.25	6	-0.42	32	38
RAC1	0.026	0.007	-10000	0	-10000	0	0
PRKCA	-0.067	0.14	0.25	3	-0.4	38	41
PRKCB	-0.068	0.14	0.24	4	-0.41	39	43
PRKCE	-0.065	0.14	0.24	3	-0.4	36	39
PRKCD	-0.06	0.13	-10000	0	-0.4	32	32
PRKCG	-0.087	0.15	0.25	2	-0.42	46	48
regulation of vascular smooth muscle contraction	-0.17	0.37	-10000	0	-1.1	69	69
PRKCQ	-0.071	0.15	0.29	3	-0.43	38	41
PLA2G4A	-0.096	0.21	0.29	2	-0.53	63	65
GNA14	-0.041	0.17	-10000	0	-0.46	71	71
GNA15	0.025	0.032	-10000	0	-0.46	2	2
GNA12	0.025	0.02	-10000	0	-0.39	1	1
GNA11	0.024	0.038	-10000	0	-0.46	3	3
Rac1/GTP	-0.038	0.22	0.34	7	-0.4	59	66
MMP1	-0.23	0.19	0.48	19	-0.35	200	219

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.014	0.13	-10000	0	-0.27	84	84
alphaM/beta2 Integrin/GPIbA	0.007	0.11	-10000	0	-0.3	49	49
alphaM/beta2 Integrin/proMMP-9	-0.17	0.15	-10000	0	-0.26	346	346
PLAUR	0.005	0.094	-10000	0	-0.39	28	28
HMGB1	0.019	0.026	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Talin	0.014	0.094	-10000	0	-0.29	35	35
AGER	0.014	0.054	-10000	0	-0.39	7	7
RAP1A	0.027	0.005	-10000	0	-10000	0	0
SELPLG	0.028	0.002	-10000	0	-10000	0	0
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	0.017	0.12	-10000	0	-0.38	20	20
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	-0.26	0.19	-10000	0	-0.39	355	355
CYR61	0.022	0.046	-10000	0	-0.4	6	6
TLN1	0.024	0.01	-10000	0	-10000	0	0
Rap1/GTP	-0.075	0.12	-10000	0	-0.35	35	35
RHOA	0.025	0.009	-10000	0	-10000	0	0
P-selectin oligomer	-0.054	0.18	-10000	0	-0.46	85	85
MYH2	-0.22	0.19	-10000	0	-0.43	180	180
MST1R	0.02	0.049	-10000	0	-0.46	5	5
leukocyte activation during inflammatory response	0.009	0.1	-10000	0	-0.32	21	21
APOB	0.003	0.078	-10000	0	-0.39	18	18
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	-0.024	0.14	-10000	0	-0.39	62	62
JAM3	0.025	0.02	-10000	0	-0.39	1	1
GP1BA	0.007	0.081	-10000	0	-0.41	18	18
alphaM/beta2 Integrin/CTGF	0.013	0.1	-10000	0	-0.3	42	42
alphaM/beta2 Integrin	-0.095	0.13	-10000	0	-0.36	49	49
JAM3 homodimer	0.025	0.02	-10000	0	-0.39	1	1
ICAM2	0.026	0.031	-10000	0	-0.46	2	2
ICAM1	0.007	0.089	-10000	0	-0.39	25	25
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.094	0.13	-10000	0	-0.36	48	48
cell adhesion	0.007	0.11	-10000	0	-0.3	49	49
NFKB1	-0.029	0.14	-10000	0	-0.38	50	50
THY1	-0.09	0.18	-10000	0	-0.39	143	143
RhoA/GDP	0.018	0.007	-10000	0	-10000	0	0
Lipoprotein(a)	0.018	0.059	-10000	0	-0.23	27	27
alphaM/beta2 Integrin/LRP/tPA	0.024	0.1	-10000	0	-0.34	20	20
IL6	-0.061	0.21	-10000	0	-0.66	46	46
ITGB2	0.008	0.072	-10000	0	-0.4	14	14
elevation of cytosolic calcium ion concentration	-0.092	0.16	-10000	0	-0.37	64	64
alphaM/beta2 Integrin/JAM2/JAM3	0.024	0.11	-10000	0	-0.33	23	23
JAM2	0.015	0.074	-10000	0	-0.46	12	12
alphaM/beta2 Integrin/ICAM1	0.024	0.12	-10000	0	-0.37	21	21
alphaM/beta2 Integrin/uPA/Plg	-0.089	0.15	-10000	0	-0.33	49	49
RhoA/GTP	-0.13	0.15	-10000	0	-0.37	93	93
positive regulation of phagocytosis	-0.063	0.11	-10000	0	-0.35	28	28
Ron/MSP	0.03	0.05	-10000	0	-0.31	10	10
alphaM/beta2 Integrin/uPAR/uPA	-0.092	0.17	-10000	0	-0.37	64	64
alphaM/beta2 Integrin/uPAR	0.004	0.12	-10000	0	-0.29	56	56
PLAU	-0.15	0.21	-10000	0	-0.39	225	225
PLAT	0.014	0.069	-10000	0	-0.39	14	14
actin filament polymerization	-0.21	0.18	0.23	1	-0.41	178	179
MST1	0.02	0.043	-10000	0	-0.4	5	5
alphaM/beta2 Integrin/lipoprotein(a)	0.013	0.1	-10000	0	-0.32	21	21
TNF	-0.04	0.14	-10000	0	-0.56	14	14
RAP1B	0.027	0.006	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.099	0.16	-10000	0	-0.25	237	237
fibrinolysis	-0.089	0.15	-10000	0	-0.33	49	49
HCK	0.024	0.029	-10000	0	-0.42	2	2
dendritic cell antigen processing and presentation	-0.094	0.13	-10000	0	-0.36	48	48
VTN	0.001	0.1	-10000	0	-0.39	32	32
alphaM/beta2 Integrin/CYR61	0.015	0.1	-10000	0	-0.29	40	40
LPA	0.001	0.059	-10000	0	-0.39	10	10
LRP1	0.027	0.022	-10000	0	-0.46	1	1
cell migration	-0.17	0.16	-10000	0	-0.38	112	112
FN1	-0.15	0.2	-10000	0	-0.39	222	222
alphaM/beta2 Integrin/Thy1	-0.056	0.16	-10000	0	-0.27	157	157
MPO	-0.002	0.11	-10000	0	-0.46	29	29
KNG1	-0.013	0.067	-10000	0	-0.39	15	15
RAP1/GDP	0.035	0.01	-10000	0	-10000	0	0
ROCK1	-0.11	0.15	-10000	0	-0.36	80	80
ELA2	0	0	-10000	0	-10000	0	0
PLG	-0.015	0.041	-10000	0	-0.39	5	5
CTGF	0.02	0.059	-10000	0	-0.44	8	8
alphaM/beta2 Integrin/Hck	0.016	0.095	-10000	0	-0.3	33	33
ITGAM	-0.006	0.1	-10000	0	-0.39	31	31
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.015	0.14	-10000	0	-0.28	98	98
HP	-0.15	0.23	-10000	0	-0.46	178	178
leukocyte adhesion	-0.049	0.14	-10000	0	-0.38	37	37
SELP	-0.054	0.18	-10000	0	-0.46	85	85

×

IL23-mediated signaling events

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
CCL2	-0.42	0.4	-10000	0	-1.2	73	73
IL23A	-0.4	0.37	-10000	0	-1.1	65	65
NF kappa B1 p50/RelA/I kappa B alpha	-0.38	0.38	-10000	0	-1.1	77	77
positive regulation of T cell mediated cytotoxicity	-0.44	0.41	-10000	0	-1.2	87	87
ITGA3	-0.4	0.36	-10000	0	-1.1	69	69
IL17F	-0.26	0.26	-10000	0	-0.7	58	58
IL12B	-0.06	0.11	-10000	0	-0.42	44	44
STAT1 (dimer)	-0.43	0.4	-10000	0	-1.1	89	89
CD4	-0.39	0.36	-10000	0	-1.1	65	65
IL23	-0.39	0.36	-10000	0	-1.1	64	64
IL23R	-0.065	0.12	-10000	0	-0.92	7	7
IL1B	-0.41	0.38	-10000	0	-1.1	69	69
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.48	0.35	-10000	0	-1.1	76	76
TYK2	-0.02	0.033	-10000	0	-0.42	1	1
STAT4	0.016	0.066	-10000	0	-0.39	13	13
STAT3	0.028	0.003	-10000	0	-10000	0	0
IL18RAP	0.007	0.084	-10000	0	-0.42	18	18
IL12RB1	-0.047	0.11	-10000	0	-0.42	37	37
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	-0.039	0.086	-10000	0	-0.31	38	38
IL23R/JAK2	-0.075	0.12	-10000	0	-0.88	6	6
positive regulation of chronic inflammatory response	-0.44	0.41	-10000	0	-1.2	87	87
natural killer cell activation	0.007	0.006	0.041	4	-10000	0	4
JAK2	-0.022	0.03	-10000	0	-10000	0	0
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
NFKB1	0.025	0.005	-10000	0	-10000	0	0
RELA	0.024	0.006	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.38	0.34	-10000	0	-1	65	65
ALOX12B	-0.46	0.43	-10000	0	-1.2	93	93
CXCL1	-0.42	0.39	-10000	0	-1.1	78	78
T cell proliferation	-0.44	0.41	-10000	0	-1.2	87	87
NFKBIA	0.024	0.007	-10000	0	-10000	0	0
IL17A	-0.2	0.2	-10000	0	-0.56	41	41
PI3K	-0.38	0.37	-10000	0	-1.1	77	77
IFNG	-0.023	0.035	0.094	5	-0.11	9	14
STAT3 (dimer)	-0.36	0.36	-10000	0	-1	68	68
IL18R1	0.021	0.032	-10000	0	-0.42	2	2
IL23/IL23R/JAK2/TYK2/SOCS3	-0.25	0.22	-10000	0	-0.74	32	32
IL18/IL18R	0.021	0.086	-10000	0	-0.28	30	30
macrophage activation	-0.023	0.015	-10000	0	-0.045	30	30
TNF	-0.41	0.38	-10000	0	-1.1	70	70
STAT3/STAT4	-0.4	0.38	-10000	0	-1.1	80	80
STAT4 (dimer)	-0.42	0.4	-10000	0	-1.1	85	85
IL18	0.009	0.074	-10000	0	-0.46	12	12
IL19	-0.53	0.5	-10000	0	-1.3	139	139
STAT5A (dimer)	-0.42	0.4	-10000	0	-1.1	85	85
STAT1	0.009	0.084	-10000	0	-0.39	22	22
SOCS3	0.027	0.022	-10000	0	-0.46	1	1
CXCL9	-0.46	0.38	-10000	0	-1.1	76	76
MPO	-0.43	0.4	-10000	0	-1.2	86	86
positive regulation of humoral immune response	-0.44	0.41	-10000	0	-1.2	87	87
IL23/IL23R/JAK2/TYK2	-0.45	0.45	-10000	0	-1.2	86	86
IL6	-0.43	0.42	-10000	0	-1.2	84	84
STAT5A	0.028	0.003	-10000	0	-10000	0	0
IL2	0.014	0.028	-10000	0	-0.38	1	1
positive regulation of tyrosine phosphorylation of STAT protein	0.007	0.006	0.041	4	-10000	0	4
CD3E	-0.4	0.36	-10000	0	-1.1	65	65
keratinocyte proliferation	-0.44	0.41	-10000	0	-1.2	87	87
NOS2	-0.42	0.38	-10000	0	-1.1	75	75

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.034	0.12	-10000	0	-0.5	25	25
Crk/p130 Cas/Paxillin	-0.067	0.12	-10000	0	-0.35	29	29
JUN	-0.043	0.12	-10000	0	-0.35	28	28
HRAS	0.026	0.02	-10000	0	-0.4	1	1
RET51/GFRalpha1/GDNF/GRB10	-0.048	0.16	-10000	0	-0.31	108	108
RAP1A	0.027	0.005	-10000	0	-10000	0	0
FRS2	0.027	0.006	-10000	0	-10000	0	0
RAP1A/GDP	0.02	0.004	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.052	0.16	-10000	0	-0.31	117	117
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.028	0.002	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.027	0.006	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.042	0.14	-10000	0	-0.27	132	132
RHOA	0.025	0.009	-10000	0	-10000	0	0
RAP1A/GTP	-0.045	0.15	-10000	0	-0.4	30	30
GRB7	0.025	0.038	-10000	0	-0.46	3	3
RET51/GFRalpha1/GDNF	-0.052	0.16	-10000	0	-0.31	118	118
MAPKKK cascade	-0.05	0.13	-10000	0	-0.37	30	30
BCAR1	0.027	0.006	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.042	0.14	-10000	0	-0.27	133	133
lamellipodium assembly	-0.046	0.12	-10000	0	-0.32	33	33
RET51/GFRalpha1/GDNF/SHC	-0.052	0.16	-10000	0	-0.31	118	118
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.04	0.14	-10000	0	-0.27	132	132
RET9/GFRalpha1/GDNF/Shank3	-0.039	0.14	-10000	0	-0.27	131	131
MAPK3	-0.059	0.14	0.34	4	-0.38	30	34
DOK1	0.027	0.018	-10000	0	-0.39	1	1
DOK6	0.016	0.063	-10000	0	-0.43	10	10
PXN	0.028	0.002	-10000	0	-10000	0	0
neurite development	-0.054	0.13	0.33	4	-0.36	28	32
DOK5	0.003	0.1	-10000	0	-0.45	25	25
GFRA1	-0.092	0.21	-10000	0	-0.46	125	125
MAPK8	-0.054	0.11	-10000	0	-0.34	34	34
HRAS/GTP	-0.049	0.15	-10000	0	-0.31	91	91
tube development	-0.036	0.13	-10000	0	-0.27	106	106
MAPK1	-0.059	0.14	0.34	4	-0.38	27	31
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.042	0.11	-10000	0	-0.26	48	48
Rac1/GDP	0.019	0.005	-10000	0	-10000	0	0
SRC	0.026	0.007	-10000	0	-10000	0	0
PDLIM7	0.022	0.041	-10000	0	-0.39	5	5
RET51/GFRalpha1/GDNF/Dok6	-0.045	0.16	-10000	0	-0.3	101	101
SHC1	0.028	0.004	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.051	0.16	-10000	0	-0.31	115	115
RET51/GFRalpha1/GDNF/Dok5	-0.062	0.18	-10000	0	-0.33	120	120
PRKCA	0.026	0.029	-10000	0	-0.42	2	2
HRAS/GDP	0.019	0.014	-10000	0	-0.28	1	1
CREB1	-0.056	0.14	-10000	0	-0.38	35	35
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.045	0.11	-10000	0	-0.25	107	107
RET51/GFRalpha1/GDNF/Grb7	-0.051	0.17	-10000	0	-0.31	115	115
mol:GDP	0	0	-10000	0	-10000	0	0
RET	-0.018	0.13	-10000	0	-0.4	55	55
DOK4	0.027	0.006	-10000	0	-10000	0	0
JNK cascade	-0.042	0.12	-10000	0	-0.34	28	28
RET9/GFRalpha1/GDNF/FRS2	-0.04	0.14	-10000	0	-0.27	128	128
SHANK3	0.027	0.005	-10000	0	-10000	0	0
RASA1	0.024	0.031	-10000	0	-0.46	2	2
NCK1	0.023	0.011	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.043	0.11	-10000	0	-0.24	106	106
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.049	0.12	-10000	0	-0.34	30	30
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.051	0.12	-10000	0	-0.34	35	35
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.051	0.12	-10000	0	-0.37	31	31
PI3K	-0.064	0.18	-10000	0	-0.48	33	33
SOS1	0.028	0.004	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.027	0.14	-10000	0	-0.27	107	107
GRB10	0.026	0.007	-10000	0	-10000	0	0
activation of MAPKK activity	-0.04	0.12	-10000	0	-0.33	29	29
RET51/GFRalpha1/GDNF/FRS2	-0.051	0.16	-10000	0	-0.31	114	114
GAB1	0.027	0.006	-10000	0	-10000	0	0
IRS1	0.024	0.038	-10000	0	-0.46	3	3
IRS2	0.025	0.031	-10000	0	-0.46	2	2
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.053	0.13	-10000	0	-0.37	33	33
RET51/GFRalpha1/GDNF/PKC alpha	-0.052	0.16	-10000	0	-0.31	116	116
GRB2	0.027	0.004	-10000	0	-10000	0	0
PRKACA	0.028	0.004	-10000	0	-10000	0	0
GDNF	-0.015	0.11	-10000	0	-0.39	38	38
RAC1	0.026	0.007	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.054	0.16	-10000	0	-0.31	119	119
Rac1/GTP	-0.048	0.14	-10000	0	-0.38	33	33
RET9/GFRalpha1/GDNF	-0.056	0.15	-10000	0	-0.3	132	132
GFRalpha1/GDNF	-0.066	0.17	-10000	0	-0.35	132	132

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.006	0.003	-10000	0	-10000	0	0
GNB1/GNG2	-0.032	0.13	-10000	0	-0.25	133	133
regulation of S phase of mitotic cell cycle	-0.028	0.096	-10000	0	-0.23	88	88
GNAO1	0.023	0.039	-10000	0	-0.41	4	4
HRAS	0.026	0.02	-10000	0	-0.4	1	1
SHBG/T-DHT	0.018	0.004	-10000	0	-10000	0	0
PELP1	0.026	0.006	-10000	0	-10000	0	0
AKT1	0.007	0.002	-10000	0	-10000	0	0
MAP2K1	-0.055	0.11	0.32	1	-0.31	15	16
T-DHT/AR	-0.076	0.16	-10000	0	-0.33	139	139
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.002	-10000	0	-0.006	65	65
GNAI2	0.024	0.009	-10000	0	-10000	0	0
GNAI3	0.027	0.005	-10000	0	-10000	0	0
GNAI1	0.026	0.022	-10000	0	-0.46	1	1
mol:GDP	-0.088	0.16	-10000	0	-0.35	130	130
cell proliferation	-0.088	0.17	0.28	3	-0.44	70	73
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
FOS	-0.11	0.27	0.3	2	-0.78	67	69
mol:Ca2+	-0.01	0.022	-10000	0	-0.071	28	28
MAPK3	-0.077	0.14	0.29	2	-0.4	33	35
MAPK1	-0.034	0.096	-10000	0	-0.32	19	19
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
mol:IP3	0	0.002	-10000	0	-0.004	66	66
cAMP biosynthetic process	0.006	0.022	0.21	2	-10000	0	2
GNG2	0.026	0.007	-10000	0	-10000	0	0
potassium channel inhibitor activity	0	0.002	-10000	0	-0.004	66	66
HRAS/GTP	-0.033	0.12	-10000	0	-0.23	127	127
actin cytoskeleton reorganization	0.027	0.027	-10000	0	-0.23	2	2
SRC	0.026	0.007	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.002	-10000	0	-0.004	66	66
PI3K	0.024	0.026	-10000	0	-0.28	2	2
apoptosis	0.07	0.16	0.43	70	-0.25	2	72
T-DHT/AR/PELP1	-0.052	0.14	-10000	0	-0.28	139	139
HRAS/GDP	-0.075	0.15	-10000	0	-0.33	127	127
CREB1	-0.075	0.17	0.26	1	-0.46	70	71
RAC1-CDC42/GTP	0.034	0.031	-10000	0	-0.23	2	2
AR	-0.11	0.22	-10000	0	-0.46	139	139
GNB1	0.027	0.006	-10000	0	-10000	0	0
RAF1	-0.048	0.11	0.33	1	-0.29	16	17
RAC1-CDC42/GDP	-0.043	0.17	-10000	0	-0.36	87	87
T-DHT/AR/PELP1/Src	-0.033	0.13	-10000	0	-0.26	129	129
MAP2K2	-0.054	0.11	0.32	1	-0.31	16	17
T-DHT/AR/PELP1/Src/PI3K	-0.029	0.097	-10000	0	-0.24	88	88
GNAZ	0.012	0.079	-10000	0	-0.41	17	17
SHBG	0.024	0.012	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.029	0.14	-10000	0	-0.48	29	29
mol:T-DHT	0	0.001	0.002	2	-0.002	41	43
RAC1	0.026	0.007	-10000	0	-10000	0	0
GNRH1	-0.004	0.054	-10000	0	-0.27	20	20
Gi family/GTP	-0.032	0.084	-10000	0	-0.28	26	26
CDC42	0.027	0.005	-10000	0	-10000	0	0

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	-0.004	0.056	-10000	0	-0.27	22	22
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	-0.003	0.11	-10000	0	-0.33	50	50
STXBP1	0.027	0.004	-10000	0	-10000	0	0
ACh/CHRNA1	-0.086	0.14	-10000	0	-0.28	178	178
RAB3GAP2/RIMS1/UNC13B	0.013	0.098	-10000	0	-0.28	49	49
mol:Ca2+	0	0	-10000	0	-10000	0	0
UniProt:P30996	0	0	-10000	0	-10000	0	0
UniProt:Q60393	0	0	-10000	0	-10000	0	0
CST086	0	0	-10000	0	-10000	0	0
RIMS1	-0.032	0.14	-10000	0	-0.46	49	49
mol:ACh	0	0.033	0.083	34	-0.11	7	41
RAB3GAP2	0.028	0.004	-10000	0	-10000	0	0
STX1A/SNAP25/VAMP2	0	0.088	-10000	0	-0.31	5	5
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	-0.086	0.14	-10000	0	-0.28	178	178
UNC13B	0.021	0.038	-10000	0	-0.46	3	3
CHRNA1	-0.14	0.22	-10000	0	-0.44	178	178
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	-0.045	0.11	-10000	0	-0.24	125	125
SNAP25	-0.004	0.034	-10000	0	-0.13	34	34
VAMP2	0.005	0.001	-10000	0	-10000	0	0
SYT1	-0.074	0.18	-10000	0	-0.39	125	125
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.014	0.051	-10000	0	-0.23	22	22
STX1A/SNAP25 fragment 1/VAMP2	0	0.088	-10000	0	-0.31	5	5

×

Coregulation of Androgen receptor activity

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
NRIP1	0.008	0.046	-10000	0	-0.46	1	1
SVIL	0.009	0.044	-10000	0	-0.46	1	1
ZNF318	0.052	0.06	0.21	3	-10000	0	3
JMJD2C	0.006	0.016	-10000	0	-0.067	14	14
T-DHT/AR/Ubc9	-0.095	0.15	-10000	0	-0.32	139	139
CARM1	0.023	0.014	-10000	0	-10000	0	0
PRDX1	0.029	0.006	-10000	0	-10000	0	0
PELP1	0.031	0.012	-10000	0	-10000	0	0
CTNNB1	0.011	0.032	-10000	0	-10000	0	0
AKT1	0.033	0.019	-10000	0	-10000	0	0
PTK2B	0.012	0.031	-10000	0	-10000	0	0
MED1	0.036	0.019	-10000	0	-10000	0	0
MAK	0.042	0.083	0.2	9	-0.39	9	18
response to oxidative stress	0.002	0.004	-10000	0	-10000	0	0
HIP1	0.009	0.043	-10000	0	-0.46	1	1
GSN	0.008	0.042	-10000	0	-10000	0	0
NCOA2	-0.013	0.12	-10000	0	-0.46	36	36
NCOA6	0.01	0.037	-10000	0	-10000	0	0
DNA-PK	0.067	0.058	0.25	2	-10000	0	2
NCOA4	0.026	0.006	-10000	0	-10000	0	0
PIAS3	0.012	0.033	-10000	0	-10000	0	0
cell proliferation	-0.01	0.12	-10000	0	-0.53	16	16
XRCC5	0.033	0.015	-10000	0	-10000	0	0
UBE3A	0.004	0.052	-10000	0	-10000	0	0
T-DHT/AR/SNURF	-0.11	0.16	-10000	0	-0.34	153	153
FHL2	-0.016	0.096	-10000	0	-0.52	6	6
RANBP9	0.011	0.037	-10000	0	-10000	0	0
JMJD1A	-0.059	0.068	-10000	0	-0.13	235	235
CDK6	0.025	0.03	-10000	0	-0.42	2	2
TGFB1I1	-0.001	0.076	-10000	0	-0.4	14	14
T-DHT/AR/CyclinD1	-0.083	0.14	-10000	0	-0.32	104	104
XRCC6	0.033	0.015	-10000	0	-10000	0	0
T-DHT/AR	-0.12	0.17	-10000	0	-0.35	143	143
CTDSP1	0.018	0.022	-10000	0	-10000	0	0
CTDSP2	0.045	0.04	-10000	0	-10000	0	0
BRCA1	0.01	0.039	-10000	0	-10000	0	0
TCF4	0.037	0.031	-10000	0	-10000	0	0
CDKN2A	-0.12	0.19	-10000	0	-0.38	187	187
SRF	0.04	0.021	-10000	0	-10000	0	0
NKX3-1	-0.13	0.13	-10000	0	-0.25	253	253
KLK3	-0.22	0.51	-10000	0	-1.4	87	87
TMF1	0.018	0.017	-10000	0	-10000	0	0
HNRNPA1	0.038	0.023	-10000	0	-10000	0	0
AOF2	-0.012	0.026	-10000	0	-0.07	86	86
APPL1	0.025	0.035	-10000	0	-10000	0	0
T-DHT/AR/Caspase 8	-0.087	0.15	-10000	0	-0.32	137	137
AR	-0.14	0.22	-10000	0	-0.49	139	139
UBA3	0.016	0.022	-10000	0	-10000	0	0
PATZ1	0.037	0.023	-10000	0	-10000	0	0
PAWR	0.021	0.017	-10000	0	-10000	0	0
PRKDC	0.03	0.017	-10000	0	-10000	0	0
PA2G4	0.039	0.026	-10000	0	-10000	0	0
UBE2I	0.028	0.004	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.08	0.14	-10000	0	-0.29	136	136
RPS6KA3	0.006	0.052	-10000	0	-0.46	2	2
T-DHT/AR/ARA70	-0.098	0.15	-10000	0	-0.32	136	136
LATS2	0.036	0.023	-10000	0	-10000	0	0
T-DHT/AR/PRX1	-0.072	0.14	0.18	1	-0.29	137	138
Cyclin D3/CDK11 p58	0.021	0.006	-10000	0	-10000	0	0
VAV3	-0.017	0.12	-10000	0	-0.47	32	32
KLK2	-0.055	0.095	-10000	0	-0.41	18	18
CASP8	0.03	0.009	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.098	0.15	-10000	0	-0.32	145	145
TMPRSS2	-0.43	0.46	-10000	0	-0.92	241	241
CCND1	0.01	0.043	-10000	0	-0.47	3	3
PIAS1	0.004	0.052	-10000	0	-0.14	1	1
mol:T-DHT	-0.023	0.03	-10000	0	-0.063	166	166
CDC2L1	0.001	0.002	-10000	0	-10000	0	0
PIAS4	-0.005	0.073	-10000	0	-0.18	15	15
T-DHT/AR/CDK6	-0.09	0.15	-10000	0	-0.32	133	133
CMTM2	0.016	0.068	-10000	0	-0.38	14	14
SNURF	-0.001	0.1	-10000	0	-0.46	23	23
ZMIZ1	-0.01	0.045	-10000	0	-10000	0	0
CCND3	0.028	0.007	-10000	0	-10000	0	0
TGIF1	0.033	0.025	-10000	0	-10000	0	0
FKBP4	0.01	0.037	-10000	0	-10000	0	0

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.096	0.13	-10000	0	-0.27	187	187
TP53	-0.031	0.065	-10000	0	-0.3	20	20
Senescence	-0.031	0.064	-10000	0	-0.3	20	20
Apoptosis	-0.031	0.064	-10000	0	-0.3	20	20
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.058	0.093	0.3	27	-10000	0	27
MDM4	0.028	0.004	-10000	0	-10000	0	0

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.021	0.033	-10000	0	-10000	0	0
NFATC2	-0.053	0.095	-10000	0	-0.31	55	55
NFATC3	-0.023	0.033	-10000	0	-10000	0	0
CD40LG	-0.23	0.26	0.35	6	-0.62	112	118
PTGS2	-0.23	0.25	0.35	5	-0.6	107	112
JUNB	0.028	0.003	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.012	0.026	-10000	0	-10000	0	0
CaM/Ca2+	-0.012	0.026	-10000	0	-10000	0	0
CALM1	0.007	0.025	-10000	0	-10000	0	0
JUN	0.007	0.027	-10000	0	-10000	0	0
mol:Ca2+	-0.012	0.012	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.008	0.014	-10000	0	-10000	0	0
FOSL1	0.018	0.059	-10000	0	-0.4	10	10
CREM	0.027	0.005	-10000	0	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.11	0.14	-10000	0	-0.39	48	48
FOS	-0.053	0.16	-10000	0	-0.47	63	63
IFNG	-0.23	0.25	0.35	4	-0.6	113	117
AP-1/NFAT1-c-4	-0.24	0.26	-10000	0	-0.62	109	109
FASLG	-0.22	0.24	0.34	4	-0.63	88	92
NFAT1-c-4/ICER1	-0.076	0.1	-10000	0	-0.32	41	41
IL2RA	-0.22	0.24	0.35	6	-0.61	92	98
FKBP12/FK506	0.02	0.005	-10000	0	-10000	0	0
CSF2	-0.29	0.27	0.35	5	-0.59	171	176
JunB/Fra1/NFAT1-c-4	-0.072	0.11	-10000	0	-0.32	39	39
IL4	-0.21	0.22	0.35	4	-0.58	79	83
IL2	-0.014	0.16	-10000	0	-0.91	15	15
IL3	-0.037	0.17	-10000	0	-0.73	28	28
FKBP1A	0.027	0.006	-10000	0	-10000	0	0
BATF3	0.024	0.037	-10000	0	-0.39	4	4
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.028	0.004	-10000	0	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	-0.031	0.14	0.3	4	-0.38	55	59
CRKL	-0.035	0.14	-10000	0	-0.4	57	57
HRAS	-0.022	0.14	-10000	0	-0.36	51	51
mol:PIP3	-0.015	0.14	0.31	1	-0.37	57	58
SPRED1	0.028	0.003	-10000	0	-10000	0	0
SPRED2	0.026	0.031	-10000	0	-0.46	2	2
GAB1	-0.035	0.15	-10000	0	-0.42	60	60
FOXO3	-0.022	0.14	0.36	1	-0.37	56	57
AKT1	-0.025	0.16	-10000	0	-0.39	65	65
BAD	-0.02	0.15	0.31	1	-0.37	56	57
megakaryocyte differentiation	-0.038	0.15	-10000	0	-0.4	63	63
GSK3B	-0.004	0.15	0.28	6	-0.37	48	54
RAF1	-0.014	0.11	0.35	1	-0.35	12	13
SHC1	0.028	0.004	-10000	0	-10000	0	0
STAT3	-0.036	0.15	-10000	0	-0.42	60	60
STAT1	-0.11	0.34	-10000	0	-1	63	63
HRAS/SPRED1	-0.004	0.12	0.3	2	-0.35	13	15
cell proliferation	-0.037	0.15	-10000	0	-0.42	60	60
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
TEC	0.006	0.097	-10000	0	-0.46	21	21
RPS6KB1	-0.026	0.15	-10000	0	-0.4	64	64
HRAS/SPRED2	-0.006	0.12	-10000	0	-0.37	14	14
LYN/TEC/p62DOK	-0.013	0.16	-10000	0	-0.42	48	48
MAPK3	-0.008	0.092	0.3	3	-0.3	8	11
STAP1	-0.047	0.15	0.25	1	-0.42	63	64
GRAP2	0.017	0.066	-10000	0	-0.43	11	11
JAK2	-0.089	0.3	-10000	0	-0.85	63	63
STAT1 (dimer)	-0.1	0.34	-10000	0	-0.97	63	63
mol:Gleevec	0	0.006	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.016	0.16	-10000	0	-0.4	58	58
actin filament polymerization	-0.038	0.14	-10000	0	-0.41	60	60
LYN	0.024	0.02	-10000	0	-0.39	1	1
STAP1/STAT5A (dimer)	-0.065	0.21	-10000	0	-0.59	62	62
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
CBL/CRKL/GRB2	-0.005	0.14	0.28	1	-0.37	52	53
PI3K	-0.013	0.14	-10000	0	-0.4	45	45
PTEN	0.027	0.006	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.12	0.4	-10000	0	-1.2	61	61
MAPK8	-0.038	0.15	-10000	0	-0.43	60	60
STAT3 (dimer)	-0.035	0.14	-10000	0	-0.41	60	60
positive regulation of transcription	-0.004	0.079	0.28	3	-0.24	7	10
mol:GDP	-0.021	0.15	-10000	0	-0.38	52	52
PIK3C2B	-0.036	0.15	-10000	0	-0.42	61	61
CBL/CRKL	-0.016	0.14	0.28	1	-0.38	55	56
FER	-0.035	0.15	-10000	0	-0.42	61	61
SH2B3	-0.035	0.15	-10000	0	-0.42	61	61
PDPK1	-0.013	0.13	0.3	1	-0.35	50	51
SNAI2	-0.034	0.14	-10000	0	-0.41	51	51
positive regulation of cell proliferation	-0.073	0.26	-10000	0	-0.72	63	63
KITLG	0.019	0.045	-10000	0	-0.48	3	3
cell motility	-0.073	0.26	-10000	0	-0.72	63	63
PTPN6	0.027	0.011	-10000	0	-10000	0	0
EPOR	-0.013	0.17	-10000	0	-0.76	13	13
STAT5A (dimer)	-0.054	0.22	-10000	0	-0.59	63	63
SOCS1	0.003	0.097	-10000	0	-0.39	30	30
cell migration	0.039	0.15	0.42	61	-10000	0	61
SOS1	0.028	0.004	-10000	0	-10000	0	0
EPO	-0.021	0.12	-10000	0	-0.39	51	51
VAV1	0.02	0.06	-10000	0	-0.45	8	8
GRB10	-0.034	0.14	-10000	0	-0.42	55	55
PTPN11	0.028	0.007	-10000	0	-10000	0	0
SCF/KIT	-0.035	0.16	-10000	0	-0.44	61	61
GO:0007205	0.002	0.008	-10000	0	-10000	0	0
MAP2K1	-0.01	0.094	0.3	3	-0.34	4	7
CBL	0.025	0.008	-10000	0	-10000	0	0
KIT	-0.13	0.43	-10000	0	-1.2	65	65
MAP2K2	-0.009	0.094	0.29	4	-0.34	4	8
SHC/Grb2/SOS1	-0.001	0.15	-10000	0	-0.4	57	57
STAT5A	-0.053	0.22	-10000	0	-0.61	63	63
GRB2	0.027	0.004	-10000	0	-10000	0	0
response to radiation	-0.033	0.14	-10000	0	-0.4	51	51
SHC/GRAP2	0.032	0.051	-10000	0	-0.3	11	11
PTPRO	-0.039	0.15	-10000	0	-0.41	63	63
SH2B2	-0.039	0.14	-10000	0	-0.42	60	60
DOK1	0.027	0.018	-10000	0	-0.39	1	1
MATK	-0.04	0.15	-10000	0	-0.43	61	61
CREBBP	0.025	0.05	-10000	0	-10000	0	0
BCL2	-0.064	0.28	-10000	0	-1	28	28

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.008	0.16	0.26	16	-0.4	43	59
FYN	-0.024	0.18	0.27	19	-0.47	43	62
LAT/GRAP2/SLP76	-0.015	0.17	0.26	5	-0.45	43	48
IKBKB	0.026	0.008	-10000	0	-10000	0	0
AKT1	-0.02	0.14	0.24	14	-0.37	43	57
B2M	0.026	0.012	-10000	0	-10000	0	0
IKBKG	-0.002	0.048	0.096	20	-0.14	10	30
MAP3K8	0.024	0.038	-10000	0	-0.46	3	3
mol:Ca2+	-0.035	0.031	-10000	0	-0.091	48	48
integrin-mediated signaling pathway	0.035	0.021	-10000	0	-0.28	2	2
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.034	0.19	0.26	16	-0.48	49	65
TRPV6	-0.19	0.26	1.1	5	-0.46	222	227
CD28	0.013	0.077	-10000	0	-0.4	17	17
SHC1	-0.031	0.18	0.27	17	-0.48	48	65
receptor internalization	-0.038	0.18	0.2	1	-0.46	65	66
PRF1	-0.044	0.21	-10000	0	-0.7	31	31
KRAS	0.026	0.007	-10000	0	-10000	0	0
GRB2	0.027	0.004	-10000	0	-10000	0	0
COT/AKT1	-0.007	0.12	0.21	13	-0.31	38	51
LAT	-0.036	0.18	0.22	14	-0.5	49	63
EntrezGene:6955	0	0.004	-10000	0	-10000	0	0
CD3D	0.011	0.077	-10000	0	-0.43	15	15
CD3E	0.013	0.071	-10000	0	-0.42	13	13
CD3G	-0.001	0.11	-10000	0	-0.44	28	28
RASGRP2	0.006	0.02	0.071	1	-0.13	2	3
RASGRP1	-0.022	0.15	0.26	14	-0.4	40	54
HLA-A	0	0.005	-10000	0	-10000	0	0
RASSF5	0.026	0.031	-10000	0	-0.46	2	2
RAP1A/GTP/RAPL	0.035	0.021	-10000	0	-0.28	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.019	0.059	0.14	34	-0.12	14	48
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.026	0.063	-10000	0	-0.22	24	24
PRKCA	-0.006	0.089	0.15	15	-0.26	23	38
GRAP2	0.017	0.066	-10000	0	-0.43	11	11
mol:IP3	0.036	0.16	0.21	172	-0.37	30	202
EntrezGene:6957	0	0.004	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.028	0.15	-10000	0	-0.45	47	47
ORAI1	0.099	0.16	0.52	3	-0.94	5	8
CSK	-0.031	0.18	0.22	15	-0.48	46	61
B7 family/CD28	-0.049	0.19	0.23	1	-0.49	50	51
CHUK	0.027	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.047	0.19	0.21	6	-0.5	56	62
PTPN6	-0.032	0.17	0.22	13	-0.45	50	63
VAV1	-0.036	0.18	0.21	13	-0.49	49	62
Monovalent TCR/CD3	-0.008	0.12	-10000	0	-0.37	35	35
CBL	0.025	0.008	-10000	0	-10000	0	0
LCK	-0.027	0.18	0.25	19	-0.48	44	63
PAG1	-0.026	0.18	0.22	30	-0.48	45	75
RAP1A	0.027	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.046	0.18	0.22	8	-0.49	55	63
CD80	-0.073	0.18	-10000	0	-0.39	121	121
CD86	0.024	0.02	-10000	0	-0.39	1	1
PDK1/CARD11/BCL10/MALT1	-0.021	0.081	-10000	0	-0.26	26	26
HRAS	0.026	0.02	-10000	0	-0.4	1	1
GO:0035030	-0.059	0.15	0.19	3	-0.42	51	54
CD8A	-0.007	0.12	-10000	0	-0.42	39	39
CD8B	-0.02	0.14	-10000	0	-0.42	54	54
PTPRC	0.017	0.069	-10000	0	-0.43	12	12
PDK1/PKC theta	-0.029	0.16	0.29	13	-0.45	39	52
CSK/PAG1	-0.022	0.17	0.22	36	-0.47	43	79
SOS1	0.028	0.004	-10000	0	-10000	0	0
peptide-MHC class I	0.019	0.013	-10000	0	-10000	0	0
GRAP2/SLP76	-0.016	0.18	0.25	5	-0.48	45	50
STIM1	0.056	0.12	1.2	4	-10000	0	4
RAS family/GTP	0.014	0.073	0.17	21	-0.18	12	33
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.04	0.2	0.2	1	-0.48	65	66
mol:DAG	-0.015	0.12	0.12	8	-0.33	35	43
RAP1A/GDP	0.012	0.029	0.081	19	-0.066	1	20
PLCG1	0.027	0.006	-10000	0	-10000	0	0
CD247	0.009	0.086	-10000	0	-0.41	21	21
cytotoxic T cell degranulation	-0.042	0.2	-10000	0	-0.67	31	31
RAP1A/GTP	0.002	0.008	-10000	0	-0.053	1	1
mol:PI-3-4-5-P3	-0.025	0.16	0.24	17	-0.4	48	65
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.032	0.2	0.23	158	-0.47	33	191
NRAS	0.027	0.005	-10000	0	-10000	0	0
ZAP70	0.007	0.092	-10000	0	-0.4	25	25
GRB2/SOS1	0.04	0.008	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.023	0.16	0.28	3	-0.46	38	41
MALT1	0.025	0.009	-10000	0	-10000	0	0
TRAF6	0.027	0.006	-10000	0	-10000	0	0
CD8 heterodimer	-0.016	0.15	-10000	0	-0.39	68	68
CARD11	0.001	0.099	-10000	0	-0.4	30	30
PRKCB	-0.007	0.093	0.15	15	-0.29	23	38
PRKCE	-0.005	0.088	0.16	12	-0.26	23	35
PRKCQ	-0.034	0.18	0.27	15	-0.49	44	59
LCP2	0.024	0.032	-10000	0	-0.39	3	3
BCL10	0.027	0.004	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.015	0.12	0.22	16	-0.32	41	57
IKK complex	0.015	0.06	0.14	45	-0.12	9	54
RAS family/GDP	-0.002	0.01	-10000	0	-0.052	1	1
MAP3K14	-0.007	0.095	0.18	14	-0.25	27	41
PDPK1	-0.018	0.13	0.24	15	-0.36	37	52
TCR/CD3/MHC I/CD8/Fyn	-0.052	0.21	-10000	0	-0.53	56	56

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.054	0.16	-10000	0	-0.41	33	33
SMAD6-7/SMURF1	0.048	0.021	-10000	0	-10000	0	0
NOG	-0.019	0.13	-10000	0	-0.42	48	48
SMAD9	-0.072	0.2	-10000	0	-0.55	66	66
SMAD4	0.025	0.008	-10000	0	-10000	0	0
SMAD5	-0.049	0.12	-10000	0	-0.42	29	29
BMP7/USAG1	-0.067	0.18	-10000	0	-0.36	133	133
SMAD5/SKI	-0.045	0.14	0.25	1	-0.42	32	33
SMAD1	0.024	0.041	-10000	0	-10000	0	0
BMP2	0.012	0.077	-10000	0	-0.39	18	18
SMAD1/SMAD1/SMAD4	0.026	0.052	-10000	0	-10000	0	0
BMPR1A	0.027	0.005	-10000	0	-10000	0	0
BMPR1B	-0.015	0.13	-10000	0	-0.4	50	50
BMPR1A-1B/BAMBI	0.014	0.1	-10000	0	-0.25	65	65
AHSG	-0.003	0.071	-10000	0	-0.39	16	16
CER1	-0.009	0.042	-10000	0	-0.39	5	5
BMP2-4/CER1	0.023	0.074	-10000	0	-0.25	31	31
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.082	0.17	-10000	0	-0.47	45	45
BMP2-4 (homodimer)	0.019	0.078	-10000	0	-0.3	27	27
RGMB	0.026	0.007	-10000	0	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	0.034	0.09	-10000	0	-0.26	12	12
RGMA	-0.029	0.16	-10000	0	-0.46	59	59
SMURF1	0.026	0.008	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.077	0.15	-10000	0	-0.41	50	50
BMP2-4/USAG1	-0.041	0.14	-10000	0	-0.28	135	135
SMAD6/SMURF1/SMAD5	-0.046	0.13	0.25	1	-0.42	30	31
SOSTDC1	-0.091	0.2	-10000	0	-0.45	124	124
BMP7/BMPR2/BMPR1A-1B	0.014	0.12	-10000	0	-0.28	44	44
SKI	0.027	0.006	-10000	0	-10000	0	0
BMP6 (homodimer)	0.021	0.046	-10000	0	-0.4	6	6
HFE2	-0.14	0.21	-10000	0	-0.46	152	152
ZFYVE16	0.026	0.007	-10000	0	-10000	0	0
MAP3K7	0.027	0.005	-10000	0	-10000	0	0
BMP2-4/CHRD	0.018	0.077	-10000	0	-0.26	32	32
SMAD5/SMAD5/SMAD4	-0.043	0.14	0.25	1	-0.42	31	32
MAPK1	0.027	0.005	-10000	0	-10000	0	0
TAK1/TAB family	-0.059	0.14	-10000	0	-0.41	32	32
BMP7 (homodimer)	-0.007	0.12	-10000	0	-0.46	35	35
NUP214	0.027	0.005	-10000	0	-10000	0	0
BMP6/FETUA	0.015	0.06	-10000	0	-0.27	20	20
SMAD1/SKI	0.025	0.068	-10000	0	-0.37	1	1
SMAD6	0.027	0.004	-10000	0	-10000	0	0
CTDSP2	0.028	0.004	-10000	0	-10000	0	0
BMP2-4/FETUA	0.015	0.077	-10000	0	-0.25	36	36
MAP3K7IP1	0	0	-10000	0	-10000	0	0
GREM1	-0.15	0.2	-10000	0	-0.39	216	216
BMPR2 (homodimer)	0.027	0.006	-10000	0	-10000	0	0
GADD34/PP1CA	0.048	0.021	-10000	0	-10000	0	0
BMPR1A-1B (homodimer)	0.008	0.097	-10000	0	-0.28	50	50
CHRDL1	-0.22	0.24	-10000	0	-0.46	259	259
ENDOFIN/SMAD1	0.028	0.067	-10000	0	-0.35	1	1
SMAD6-7/SMURF1/SMAD1	0.044	0.067	-10000	0	-10000	0	0
SMAD6/SMURF1	0.026	0.008	-10000	0	-10000	0	0
BAMBI	0.012	0.083	-10000	0	-0.44	17	17
SMURF2	0.028	0.004	-10000	0	-10000	0	0
BMP2-4/CHRDL1	-0.12	0.18	-10000	0	-0.3	246	246
BMP2-4/GREM1	-0.072	0.15	-10000	0	-0.24	209	209
SMAD7	0.026	0.008	-10000	0	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.066	0.2	-10000	0	-0.51	74	74
SMAD1/SMAD6	0.023	0.068	-10000	0	-0.35	1	1
TAK1/SMAD6	0.037	0.013	-10000	0	-10000	0	0
BMP7	-0.007	0.12	-10000	0	-0.46	35	35
BMP6	0.021	0.046	-10000	0	-0.4	6	6
MAP3K7IP2	0	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.065	0.15	-10000	0	-0.41	46	46
PPM1A	0.026	0.007	-10000	0	-10000	0	0
SMAD1/SMURF2	0.026	0.069	-10000	0	-0.37	1	1
SMAD7/SMURF1	0.035	0.015	-10000	0	-10000	0	0
CTDSPL	0.024	0.009	-10000	0	-10000	0	0
PPP1CA	0.025	0.008	-10000	0	-10000	0	0
XIAP	0.028	0.004	-10000	0	-10000	0	0
CTDSP1	0.027	0.006	-10000	0	-10000	0	0
PPP1R15A	0.027	0.004	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.11	0.16	-10000	0	-0.42	70	70
CHRD	0.01	0.064	-10000	0	-0.39	12	12
BMPR2	0.027	0.006	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.085	0.16	-10000	0	-0.4	63	63
BMP4	0.017	0.067	-10000	0	-0.46	10	10
FST	-0.11	0.19	-10000	0	-0.39	166	166
BMP2-4/NOG	0.007	0.11	-10000	0	-0.26	71	71
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	0.021	0.11	-10000	0	-0.41	5	5

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.027	0.004	-10000	0	-10000	0	0
GNAT1/GTP	0.013	0.023	-10000	0	-0.27	3	3
Metarhodopsin II/Arrestin	0.021	0.022	-10000	0	-0.23	3	3
PDE6G/GNAT1/GTP	0.021	0.048	-10000	0	-0.23	17	17
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	0.003	0.037	-10000	0	-0.39	3	3
GRK1	-0.01	0.03	-10000	0	-0.39	2	2
CNG Channel	-0.21	0.17	-10000	0	-0.42	158	158
mol:Na +	-0.11	0.14	-10000	0	-0.38	48	48
mol:ADP	-0.01	0.03	-10000	0	-0.39	2	2
RGS9-1/Gbeta5/R9AP	0.041	0.062	-10000	0	-0.26	20	20
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	-0.11	0.14	-10000	0	-0.39	48	48
CNGB1	-0.18	0.21	-10000	0	-0.39	260	260
RDH5	0.026	0.028	-10000	0	-0.42	2	2
SAG	-0.012	0.016	-10000	0	-10000	0	0
mol:Ca2+	-0.11	0.15	0.38	7	-0.38	47	54
Na + (4 Units)	-0.11	0.13	-10000	0	-0.36	48	48
RGS9	0.017	0.065	-10000	0	-0.4	12	12
GNB1/GNGT1	-0.003	0.1	-10000	0	-0.27	64	64
GNAT1/GDP	0.041	0.062	-10000	0	-0.26	13	13
GUCY2D	0.006	0.088	-10000	0	-0.39	24	24
GNGT1	-0.031	0.14	-10000	0	-0.39	64	64
GUCY2F	-0.009	0.026	-10000	0	-0.39	1	1
GNB5	0.027	0.004	-10000	0	-10000	0	0
mol:GMP (4 units)	-0.11	0.14	-10000	0	-0.26	218	218
mol:11-cis-retinal	0.026	0.028	-10000	0	-0.42	2	2
mol:cGMP	0.007	0.09	-10000	0	-0.33	5	5
GNB1	0.027	0.006	-10000	0	-10000	0	0
Rhodopsin	0.028	0.034	-10000	0	-0.29	5	5
SLC24A1	0.027	0.004	-10000	0	-10000	0	0
CNGA1	-0.006	0.12	-10000	0	-0.46	34	34
Metarhodopsin II	0.02	0.023	-10000	0	-0.21	4	4
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.015	0.097	-10000	0	-0.33	4	4
RGS9BP	0.017	0.065	-10000	0	-0.46	9	9
Metarhodopsin II/Transducin	-0.007	0.054	-10000	0	-0.27	10	10
GCAP Family/Ca ++	0.012	0.08	-10000	0	-0.21	54	54
PDE6A/B	-0.14	0.2	-10000	0	-0.34	238	238
mol:Pi	0.04	0.062	-10000	0	-0.26	20	20
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	0.007	0.084	-10000	0	-0.2	67	67
PDE6B	-0.009	0.12	-10000	0	-0.43	39	39
PDE6A	-0.18	0.24	-10000	0	-0.46	215	215
PDE6G	0.016	0.068	-10000	0	-0.39	14	14
RHO	-0.005	0.036	-10000	0	-0.39	3	3
PDE6	-0.091	0.17	-10000	0	-0.4	36	36
GUCA1A	-0.018	0.13	-10000	0	-0.39	54	54
GC2/GCAP Family	0.02	0.087	-10000	0	-0.31	3	3
GUCA1C	-0.016	0.006	-10000	0	-10000	0	0
GUCA1B	0.023	0.042	-10000	0	-0.44	4	4

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.028	0.063	-10000	0	-0.33	15	15
Necdin/E2F1	0.02	0.079	-10000	0	-0.31	26	26
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0	0.13	-10000	0	-0.28	32	32
NGF (dimer)/p75(NTR)/BEX1	-0.034	0.14	-10000	0	-0.24	149	149
NT-4/5 (dimer)/p75(NTR)	0.022	0.08	-10000	0	-0.32	26	26
IKBKB	0.026	0.008	-10000	0	-10000	0	0
AKT1	0.004	0.12	-10000	0	-0.37	1	1
IKBKG	0.027	0.006	-10000	0	-10000	0	0
BDNF	-0.004	0.12	-10000	0	-0.43	35	35
MGDIs/NGR/p75(NTR)/LINGO1	0.011	0.11	-10000	0	-0.26	64	64
FURIN	0.027	0.004	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	0.007	0.12	-10000	0	-0.27	71	71
LINGO1	-0.006	0.11	-10000	0	-0.39	41	41
Sortilin/TRAF6/NRIF	0.026	0.045	-10000	0	-10000	0	0
proBDNF (dimer)	-0.004	0.12	-10000	0	-0.43	35	35
NTRK1	-0.007	0.12	-10000	0	-0.39	43	43
RTN4R	0.015	0.07	-10000	0	-0.39	15	15
neuron apoptosis	-0.039	0.13	0.46	1	-0.43	27	28
IRAK1	0.027	0.006	-10000	0	-10000	0	0
SHC1	-0.042	0.11	-10000	0	-0.24	119	119
ARHGDIA	0.027	0.004	-10000	0	-10000	0	0
RhoA/GTP	0.018	0.007	-10000	0	-10000	0	0
Gamma Secretase	0.075	0.026	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.01	0.13	-10000	0	-0.29	35	35
MAGEH1	0.027	0.019	-10000	0	-0.39	1	1
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.014	0.14	-10000	0	-0.31	42	42
Mammalian IAPs/DIABLO	0.054	0.05	-10000	0	-10000	0	0
proNGF (dimer)	-0.054	0.16	-10000	0	-0.39	98	98
MAGED1	0.024	0.04	-10000	0	-0.42	4	4
APP	0.026	0.019	-10000	0	-0.39	1	1
NT-4/5 (dimer)	0.025	0.034	-10000	0	-0.41	3	3
ZNF274	0.027	0.006	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.019	0.1	-10000	0	-0.25	17	17
NGF	-0.054	0.16	-10000	0	-0.39	98	98
cell cycle arrest	-0.065	0.1	-10000	0	-0.32	18	18
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.005	0.066	-10000	0	-0.25	6	6
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.037	0.071	-10000	0	-0.27	24	24
NCSTN	0.027	0.004	-10000	0	-10000	0	0
mol:GTP	-0.016	0.12	-10000	0	-0.24	123	123
PSENEN	0.027	0.005	-10000	0	-10000	0	0
mol:ceramide	-0.047	0.11	-10000	0	-0.29	34	34
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.001	0.048	-10000	0	-0.31	1	1
p75(NTR)/beta APP	0.022	0.076	-10000	0	-0.3	27	27
BEX1	-0.01	0.1	-10000	0	-0.39	35	35
mol:GDP	-0.052	0.1	-10000	0	-0.24	122	122
NGF (dimer)	-0.077	0.15	-10000	0	-0.25	178	178
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.025	0.11	-10000	0	-0.32	17	17
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
RAC1/GTP	-0.01	0.1	-10000	0	-0.2	112	112
MYD88	0.024	0.009	-10000	0	-10000	0	0
CHUK	0.027	0.005	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.016	0.13	-10000	0	-0.24	123	123
RHOB	0.028	0.003	-10000	0	-10000	0	0
RHOA	0.025	0.009	-10000	0	-10000	0	0
MAGE-G1/E2F1	0.025	0.061	-10000	0	-0.27	20	20
NT3 (dimer)	-0.11	0.22	-10000	0	-0.46	144	144
TP53	-0.015	0.095	0.53	1	-0.45	5	6
PRDM4	-0.048	0.11	-10000	0	-0.29	35	35
BDNF (dimer)	-0.2	0.17	-10000	0	-0.29	358	358
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
SORT1	0.011	0.088	-10000	0	-0.46	17	17
activation of caspase activity	-0.005	0.13	-10000	0	-0.28	32	32
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.008	0.13	-10000	0	-0.29	31	31
RHOC	0.027	0.005	-10000	0	-10000	0	0
XIAP	0.028	0.004	-10000	0	-10000	0	0
MAPK10	-0.044	0.12	0.31	3	-0.38	20	23
DIABLO	0.028	0.002	-10000	0	-10000	0	0
SMPD2	-0.047	0.11	-10000	0	-0.29	34	34
APH1B	0.028	0.004	-10000	0	-10000	0	0
APH1A	0.027	0.005	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.026	0.14	-10000	0	-0.25	134	134
PSEN1	0.027	0.006	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.04	0.009	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.081	0.18	-10000	0	-0.34	161	161
MAPK8	-0.036	0.1	0.35	2	-0.38	10	12
MAPK9	-0.035	0.11	0.34	3	-0.38	10	13
APAF1	0.028	0.002	-10000	0	-10000	0	0
NTF3	-0.11	0.22	-10000	0	-0.46	144	144
NTF4	0.025	0.034	-10000	0	-0.41	3	3
NDN	0.019	0.064	-10000	0	-0.46	9	9
RAC1/GDP	0.019	0.005	-10000	0	-10000	0	0
RhoA-B-C/GDP	0.004	0.11	-10000	0	-0.35	1	1
p75 CTF/Sortilin/TRAF6/NRIF	0.054	0.061	-10000	0	-0.26	16	16
RhoA-B-C/GTP	-0.017	0.12	-10000	0	-0.24	123	123
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.033	0.11	-10000	0	-0.27	37	37
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.023	0.11	-10000	0	-0.28	38	38
PRKACB	0.026	0.022	-10000	0	-0.46	1	1
proBDNF (dimer)/p75 ECD	0.015	0.089	-10000	0	-0.31	36	36
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.012	0.071	-10000	0	-0.39	15	15
BIRC2	0.024	0.01	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.049	0.1	0.21	1	-0.3	30	31
BAD	-0.039	0.11	0.38	2	-0.38	11	13
RIPK2	0.025	0.009	-10000	0	-10000	0	0
NGFR	0.005	0.098	-10000	0	-0.42	26	26
CYCS	-0.043	0.1	-10000	0	-0.42	7	7
ADAM17	0.026	0.031	-10000	0	-0.46	2	2
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.003	0.11	-10000	0	-0.27	15	15
BCL2L11	-0.04	0.11	0.38	2	-0.38	11	13
BDNF (dimer)/p75(NTR)	0	0.11	-10000	0	-0.3	60	60
PI3K	-0.01	0.11	-10000	0	-0.26	17	17
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.01	0.13	-10000	0	-0.29	35	35
NDNL2	0.028	0.004	-10000	0	-10000	0	0
YWHAE	0.027	0.006	-10000	0	-10000	0	0
PRKCI	0.02	0.013	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.037	0.14	-10000	0	-0.28	122	122
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.012	0.14	-10000	0	-0.3	38	38
TRAF6	0.027	0.006	-10000	0	-10000	0	0
RAC1	0.026	0.007	-10000	0	-10000	0	0
PRKCZ	0.026	0.022	-10000	0	-0.46	1	1
PLG	-0.015	0.041	-10000	0	-0.39	5	5
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.049	0.12	-10000	0	-0.32	49	49
SQSTM1	0.026	0.007	-10000	0	-10000	0	0
NGFRAP1	0.026	0.026	-10000	0	-0.39	2	2
CASP3	-0.037	0.1	0.37	2	-0.34	16	18
E2F1	0.01	0.08	-10000	0	-0.39	20	20
CASP9	0.027	0.006	-10000	0	-10000	0	0
IKK complex	0.008	0.11	-10000	0	-0.36	1	1
NGF (dimer)/TRKA	-0.045	0.14	-10000	0	-0.29	132	132
MMP7	-0.11	0.19	-10000	0	-0.39	160	160
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.002	0.13	-10000	0	-0.28	29	29
MMP3	-0.24	0.2	-10000	0	-0.39	322	322
APAF-1/Caspase 9	-0.032	0.088	-10000	0	-0.36	5	5

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	0.034	0.066	-10000	0	-0.27	19	19
fibroblast growth factor receptor signaling pathway	0.034	0.065	-10000	0	-0.27	19	19
LAMA1	-0.14	0.2	-10000	0	-0.39	207	207
PRNP	0.026	0.007	-10000	0	-10000	0	0
GPC1/SLIT2	-0.008	0.12	-10000	0	-0.33	63	63
SMAD2	0.016	0.028	-10000	0	-0.26	1	1
GPC1/PrPc/Cu2+	0.034	0.017	-10000	0	-0.23	1	1
GPC1/Laminin alpha1	-0.09	0.15	-10000	0	-0.27	207	207
TDGF1	0.003	0.048	-10000	0	-0.39	6	6
CRIPTO/GPC1	0.029	0.038	-10000	0	-0.27	7	7
APP/GPC1	0.037	0.022	-10000	0	-0.27	2	2
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0.003	0.024	-10000	0	-0.22	3	3
FLT1	0.026	0.019	-10000	0	-0.39	1	1
GPC1/TGFB/TGFBR1/TGFBR2	0.046	0.031	-10000	0	-0.27	2	2
SERPINC1	0.014	0.061	-10000	0	-0.39	11	11
FYN	0.001	0.032	-10000	0	-0.23	6	6
FGR	0.001	0.031	-10000	0	-0.23	7	7
positive regulation of MAPKKK cascade	0.003	0.095	0.3	8	-0.35	9	17
SLIT2	-0.033	0.16	-10000	0	-0.46	62	62
GPC1/NRG	-0.01	0.11	-10000	0	-0.28	75	75
NRG1	-0.035	0.15	-10000	0	-0.39	74	74
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.046	0.038	-10000	0	-0.23	7	7
LYN	0.001	0.032	-10000	0	-0.23	6	6
mol:Spermine	0.007	0.012	-10000	0	-0.27	1	1
cell growth	0.034	0.065	-10000	0	-0.27	19	19
BMP signaling pathway	-0.026	0.019	0.39	1	-10000	0	1
SRC	0.001	0.03	-10000	0	-0.23	5	5
TGFBR1	0.027	0.005	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.28	0.24	-10000	0	-0.46	320	320
GPC1	0.026	0.019	-10000	0	-0.39	1	1
TGFBR1 (dimer)	0.027	0.005	-10000	0	-10000	0	0
VEGFA	0.022	0.045	-10000	0	-0.39	6	6
BLK	-0.031	0.084	-10000	0	-0.24	73	73
HCK	0.001	0.034	-10000	0	-0.26	7	7
FGF2	0.011	0.085	-10000	0	-0.44	17	17
FGFR1	0.019	0.047	-10000	0	-0.4	6	6
VEGFR1 homodimer	0.026	0.019	-10000	0	-0.39	1	1
TGFBR2	0.022	0.032	-10000	0	-0.46	2	2
cell death	0.037	0.022	-10000	0	-0.27	2	2
ATIII/GPC1	0.031	0.048	-10000	0	-0.27	12	12
PLA2G2A/GPC1	-0.19	0.18	-10000	0	-0.33	321	321
LCK	-0.004	0.045	-10000	0	-0.23	18	18
neuron differentiation	-0.01	0.11	-10000	0	-0.28	75	75
PrPc/Cu2+	0.02	0.005	-10000	0	-10000	0	0
APP	0.026	0.019	-10000	0	-0.39	1	1
TGFBR2 (dimer)	0.022	0.032	-10000	0	-0.46	2	2

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.026	0.017	0.22	2	-10000	0	2
AES	0.026	0.015	0.21	1	-10000	0	1
FBXW11	0.027	0.006	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.035	0.03	-10000	0	-0.31	3	3
SMAD4	0.025	0.008	-10000	0	-10000	0	0
DKK2	0.015	0.074	-10000	0	-0.42	14	14
TLE1	0.026	0.015	0.21	1	-10000	0	1
MACF1	0.028	0.005	-10000	0	-10000	0	0
CTNNB1	0.037	0.12	0.26	19	-0.39	11	30
WIF1	-0.2	0.23	-10000	0	-0.46	221	221
beta catenin/RanBP3	-0.006	0.1	0.38	15	-0.4	5	20
KREMEN2	-0.12	0.2	-10000	0	-0.39	178	178
DKK1	-0.13	0.2	-10000	0	-0.39	191	191
beta catenin/beta TrCP1	0.049	0.12	0.26	19	-0.36	9	28
FZD1	0.025	0.029	-10000	0	-0.42	2	2
AXIN2	-0.015	0.2	0.68	4	-1.3	10	14
AXIN1	0.028	0.004	-10000	0	-10000	0	0
RAN	0.028	0.003	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.027	0.092	-10000	0	-0.56	10	10
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.041	0.14	0.33	2	-0.54	15	17
Axin1/APC/GSK3	0.042	0.07	0.25	5	-0.35	4	9
Axin1/APC/GSK3/beta catenin/Macf1	0.04	0.098	0.3	8	-0.39	7	15
HNF1A	0.019	0.06	0.22	1	-0.39	10	11
CTBP1	0.025	0.017	0.2	2	-10000	0	2
MYC	0.12	0.24	0.57	101	-10000	0	101
RANBP3	0.027	0.005	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.05	0.14	-10000	0	-0.23	175	175
NKD1	0.012	0.077	-10000	0	-0.39	18	18
TCF4	0.024	0.017	0.22	1	-10000	0	1
TCF3	0.026	0.015	0.22	1	-10000	0	1
WNT1/LRP6/FZD1/Axin1	0.056	0.044	-10000	0	-0.26	2	2
Ran/GTP	0.02	0.003	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	-0.002	0.11	0.46	13	-0.45	7	20
LEF1	0.022	0.044	0.22	1	-0.39	5	6
DVL1	0.048	0.066	0.23	1	-0.47	3	4
CSNK2A1	0.027	0.007	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.059	0.11	0.29	2	-0.52	9	11
DKK1/LRP6/Kremen 2	-0.13	0.18	-10000	0	-0.28	284	284
LRP6	0.026	0.023	-10000	0	-0.46	1	1
CSNK1A1	0.026	0.018	0.22	2	-10000	0	2
NLK	0.027	0.008	-10000	0	-10000	0	0
CCND1	0.14	0.28	0.58	126	-1.2	4	130
WNT1	0.016	0.05	-10000	0	-0.39	7	7
GSK3A	0.028	0.005	-10000	0	-10000	0	0
GSK3B	0.025	0.009	-10000	0	-10000	0	0
FRAT1	0.027	0.004	-10000	0	-10000	0	0
PPP2R5D	0.036	0.078	0.24	10	-0.4	7	17
APC	0.026	0.067	0.35	5	-10000	0	5
WNT1/LRP6/FZD1	0.079	0.096	0.21	167	-10000	0	167
CREBBP	0.026	0.016	0.22	1	-10000	0	1

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.12	0.13	-10000	0	-0.41	12	12
NF kappa B1 p50/RelA/I kappa B alpha	-0.11	0.13	0.32	1	-0.4	10	11
alphaV/beta3 Integrin/Osteopontin/Src	-0.14	0.15	-10000	0	-0.28	267	267
AP1	-0.16	0.17	-10000	0	-0.47	57	57
ILK	-0.12	0.12	-10000	0	-0.41	12	12
bone resorption	-0.095	0.12	0.33	1	-0.38	15	16
PTK2B	0.026	0.008	-10000	0	-10000	0	0
PYK2/p130Cas	-0.083	0.14	-10000	0	-0.39	13	13
ITGAV	0.022	0.029	-10000	0	-0.4	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.032	0.049	-10000	0	-0.33	9	9
alphaV/beta3 Integrin/Osteopontin	-0.12	0.15	-10000	0	-0.32	54	54
MAP3K1	-0.12	0.13	-10000	0	-0.38	18	18
JUN	0.027	0.005	-10000	0	-10000	0	0
MAPK3	-0.14	0.13	-10000	0	-0.34	47	47
MAPK1	-0.14	0.13	-10000	0	-0.32	50	50
Rac1/GDP	0.019	0.005	-10000	0	-10000	0	0
NFKB1	0.027	0.005	-10000	0	-10000	0	0
MAPK8	-0.12	0.12	-10000	0	-0.39	17	17
ITGB3	0.006	0.089	-10000	0	-0.42	21	21
NFKBIA	-0.13	0.13	-10000	0	-0.39	17	17
FOS	-0.034	0.16	-10000	0	-0.46	63	63
CD44	0.025	0.023	-10000	0	-0.46	1	1
CHUK	0.027	0.005	-10000	0	-10000	0	0
PLAU	-0.2	0.19	-10000	0	-0.5	41	41
NF kappa B1 p50/RelA	-0.12	0.15	-10000	0	-0.44	8	8
BCAR1	0.027	0.006	-10000	0	-10000	0	0
RELA	0.027	0.006	-10000	0	-10000	0	0
alphaV beta3 Integrin	0.011	0.074	-10000	0	-0.3	23	23
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	-0.12	0.13	-10000	0	-0.38	18	18
VAV3	-0.13	0.13	-10000	0	-0.41	34	34
MAP3K14	-0.13	0.13	-10000	0	-0.37	22	22
ROCK2	0.019	0.064	-10000	0	-0.46	9	9
SPP1	-0.2	0.21	-10000	0	-0.39	279	279
RAC1	0.026	0.007	-10000	0	-10000	0	0
Rac1/GTP	-0.11	0.12	-10000	0	-0.38	33	33
MMP2	-0.15	0.17	-10000	0	-0.48	69	69

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.038	0.022	-10000	0	-0.27	2	2
VLDLR	0.02	0.049	-10000	0	-0.46	5	5
CRKL	0.026	0.019	-10000	0	-0.39	1	1
LRPAP1	0.026	0.007	-10000	0	-10000	0	0
FYN	0.027	0.019	-10000	0	-0.39	1	1
ITGA3	0.012	0.079	-10000	0	-0.39	19	19
RELN/VLDLR/Fyn	-0.021	0.13	-10000	0	-0.28	102	102
MAPK8IP1/MKK7/MAP3K11/JNK1	0.068	0.044	-10000	0	-10000	0	0
AKT1	-0.023	0.081	-10000	0	-0.34	7	7
MAP2K7	0.027	0.004	-10000	0	-10000	0	0
RAPGEF1	0.027	0.005	-10000	0	-10000	0	0
DAB1	-0.001	0.073	-10000	0	-0.39	16	16
RELN/LRP8/DAB1	-0.026	0.13	-10000	0	-0.26	120	120
LRPAP1/LRP8	0.033	0.044	-10000	0	-0.27	10	10
RELN/LRP8/DAB1/Fyn	-0.015	0.13	-10000	0	-0.25	100	100
DAB1/alpha3/beta1 Integrin	-0.023	0.12	-10000	0	-0.4	6	6
long-term memory	-0.059	0.16	-10000	0	-0.44	30	30
DAB1/LIS1	-0.009	0.13	-10000	0	-0.39	6	6
DAB1/CRLK/C3G	-0.017	0.12	-10000	0	-0.39	7	7
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
DAB1/NCK2	-0.008	0.13	-10000	0	-0.4	6	6
ARHGEF2	0.028	0.004	-10000	0	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	-0.069	0.18	-10000	0	-0.43	105	105
CDK5R1	0.026	0.026	-10000	0	-0.39	2	2
RELN	-0.073	0.2	-10000	0	-0.46	103	103
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
RELN/LRP8/Fyn	-0.022	0.14	-10000	0	-0.28	111	111
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.058	0.17	-10000	0	-0.31	97	97
MAPK8	0.022	0.053	-10000	0	-0.46	6	6
RELN/VLDLR/DAB1	-0.026	0.12	-10000	0	-0.26	113	113
ITGB1	0.027	0.005	-10000	0	-10000	0	0
MAP1B	-0.038	0.13	0.2	1	-0.29	48	49
RELN/LRP8	-0.022	0.14	-10000	0	-0.28	109	109
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.01	0.13	-10000	0	-0.26	78	78
PI3K	0.027	0.03	-10000	0	-0.33	2	2
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.028	0.06	-10000	0	-0.28	19	19
RAP1A	-0.029	0.13	0.32	11	-0.39	6	17
PAFAH1B1	0.027	0.006	-10000	0	-10000	0	0
MAPK8IP1	0.024	0.034	-10000	0	-0.41	3	3
CRLK/C3G	0.038	0.018	-10000	0	-0.27	1	1
GRIN2B	-0.009	0.043	-10000	0	-0.39	5	5
NCK2	0.028	0.003	-10000	0	-10000	0	0
neuron differentiation	-0.014	0.089	-10000	0	-0.34	8	8
neuron adhesion	-0.034	0.12	0.33	10	-0.37	7	17
LRP8	0.02	0.057	-10000	0	-0.39	10	10
GSK3B	-0.013	0.088	-10000	0	-0.32	8	8
RELN/VLDLR/DAB1/Fyn	-0.016	0.12	-10000	0	-0.25	99	99
MAP3K11	0.027	0.006	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.022	0.09	-10000	0	-0.24	67	67
CDK5	0.026	0.007	-10000	0	-10000	0	0
MAPT	-0.19	0.22	0.8	1	-0.43	227	228
neuron migration	-0.023	0.14	0.3	9	-0.42	3	12
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.014	0.09	-10000	0	-0.34	8	8
RELN/VLDLR	-0.012	0.13	-10000	0	-0.26	96	96

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.18	0.27	-10000	0	-0.9	24	24
PCK1	-0.45	0.58	-10000	0	-1.2	170	170
HNF4A	-0.2	0.3	-10000	0	-1	26	26
KCNJ11	-0.27	0.4	-10000	0	-1	79	79
AKT1	-0.091	0.15	-10000	0	-0.57	5	5
response to starvation	-0.003	0.017	-10000	0	-0.2	1	1
DLK1	-0.34	0.46	-10000	0	-1	142	142
NKX2-1	-0.015	0.18	0.32	47	-0.4	12	59
ACADM	-0.18	0.28	-10000	0	-0.95	23	23
TAT	-0.13	0.19	-10000	0	-0.74	11	11
CEBPB	0.027	0.008	-10000	0	-10000	0	0
CEBPA	0.025	0.038	-10000	0	-0.46	3	3
TTR	-0.26	0.29	-10000	0	-0.87	56	56
PKLR	-0.2	0.29	-10000	0	-0.89	32	32
APOA1	-0.21	0.32	-10000	0	-1	25	25
CPT1C	-0.18	0.27	-10000	0	-0.89	26	26
ALAS1	-0.085	0.16	-10000	0	-0.61	8	8
TFRC	-0.16	0.22	-10000	0	-0.76	13	13
FOXF1	0.021	0.05	-10000	0	-0.4	7	7
NF1	0.033	0.005	-10000	0	-10000	0	0
HNF1A (dimer)	0.018	0.062	-10000	0	-0.38	10	10
CPT1A	-0.16	0.27	-10000	0	-0.9	21	21
HMGCS1	-0.16	0.27	-10000	0	-0.88	23	23
NR3C1	0.028	0.024	-10000	0	-10000	0	0
CPT1B	-0.19	0.28	-10000	0	-0.92	30	30
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.026	0.023	-10000	0	-10000	0	0
GCK	-0.19	0.28	-10000	0	-0.89	27	27
CREB1	-0.037	0.099	-10000	0	-0.23	36	36
IGFBP1	-0.082	0.15	-10000	0	-0.66	4	4
PDX1	-0.094	0.17	-10000	0	-0.73	4	4
UCP2	-0.17	0.27	-10000	0	-0.89	26	26
ALDOB	-0.2	0.3	-10000	0	-0.93	29	29
AFP	-0.15	0.17	-10000	0	-0.47	52	52
BDH1	-0.15	0.27	-10000	0	-0.94	18	18
HADH	-0.19	0.29	-10000	0	-0.95	22	22
F2	-0.22	0.32	-10000	0	-1.1	23	23
HNF1A	0.018	0.062	-10000	0	-0.38	10	10
G6PC	-0.054	0.1	-10000	0	-10000	0	0
SLC2A2	-0.1	0.17	-10000	0	-0.74	3	3
INS	-0.023	0.032	-10000	0	-0.4	2	2
FOXA1	-0.16	0.24	-10000	0	-0.47	189	189
FOXA3	-0.094	0.17	-10000	0	-0.42	70	70
FOXA2	-0.22	0.33	-10000	0	-0.99	32	32
ABCC8	-0.19	0.29	-10000	0	-0.95	22	22
ALB	-0.16	0.18	-10000	0	-0.51	65	65

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.026	0.019	-10000	0	-0.39	1	1
RAS family/GTP/Tiam1	-0.06	0.1	-10000	0	-0.24	66	66
NT3 (dimer)/TRKC	-0.14	0.22	-10000	0	-0.39	215	215
NT3 (dimer)/TRKB	-0.13	0.21	-10000	0	-0.35	227	227
SHC/Grb2/SOS1/GAB1/PI3K	0.021	0.022	-10000	0	-10000	0	0
RAPGEF1	0.027	0.005	-10000	0	-10000	0	0
BDNF	-0.004	0.12	-10000	0	-0.43	35	35
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
DYNLT1	0.027	0.005	-10000	0	-10000	0	0
NTRK1	-0.007	0.12	-10000	0	-0.39	43	43
NTRK2	-0.097	0.21	-10000	0	-0.45	134	134
NTRK3	-0.098	0.21	-10000	0	-0.46	127	127
NT-4/5 (dimer)/TRKB	-0.046	0.16	-10000	0	-0.28	151	151
neuron apoptosis	0.041	0.12	0.36	20	-10000	0	20
SHC 2-3/Grb2	-0.044	0.13	-10000	0	-0.39	20	20
SHC1	0.028	0.004	-10000	0	-10000	0	0
SHC2	-0.046	0.12	-10000	0	-0.38	27	27
SHC3	-0.041	0.12	-10000	0	-0.43	18	18
STAT3 (dimer)	0.025	0.058	-10000	0	-0.34	13	13
NT3 (dimer)/TRKA	-0.075	0.17	-10000	0	-0.29	187	187
RIN/GDP	-0.028	0.097	0.2	13	-0.24	11	24
GIPC1	0.028	0.004	-10000	0	-10000	0	0
KRAS	0.026	0.007	-10000	0	-10000	0	0
DNAJA3	-0.012	0.086	0.21	2	-0.26	16	18
RIN/GTP	0.012	0.004	-10000	0	-10000	0	0
CCND1	0.011	0.057	-10000	0	-0.72	3	3
MAGED1	0.024	0.04	-10000	0	-0.42	4	4
PTPN11	0.028	0.002	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.025	0.034	-10000	0	-0.41	3	3
SHC/GRB2/SOS1	0.054	0.013	-10000	0	-10000	0	0
GRB2	0.027	0.004	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.031	0.14	-10000	0	-0.25	140	140
TRKA/NEDD4-2	0.012	0.084	-10000	0	-0.27	41	41
ELMO1	0.025	0.029	-10000	0	-0.42	2	2
RhoG/GTP/ELMO1/DOCK1	0.033	0.025	-10000	0	-0.26	3	3
NGF	-0.054	0.16	-10000	0	-0.39	98	98
HRAS	0.026	0.02	-10000	0	-0.4	1	1
DOCK1	0.027	0.022	-10000	0	-0.46	1	1
GAB2	0.022	0.038	-10000	0	-0.46	3	3
RIT2	-0.015	0.011	-10000	0	-10000	0	0
RIT1	0.027	0.004	-10000	0	-10000	0	0
FRS2	0.027	0.006	-10000	0	-10000	0	0
DNM1	0	0.1	-10000	0	-0.39	34	34
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.027	0.006	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.002	0.089	0.22	1	-0.28	13	14
mol:GDP	-0.044	0.13	0.25	13	-0.34	17	30
NGF (dimer)	-0.054	0.16	-10000	0	-0.39	98	98
RhoG/GDP	0.018	0.021	-10000	0	-0.3	2	2
RIT1/GDP	-0.026	0.097	0.19	12	-0.24	11	23
TIAM1	0.021	0.053	-10000	0	-0.46	6	6
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
BDNF (dimer)/TRKB	-0.051	0.16	-10000	0	-0.28	158	158
KIDINS220/CRKL/C3G	0.038	0.018	-10000	0	-0.27	1	1
SHC/RasGAP	0.038	0.02	-10000	0	-0.33	1	1
FRS2 family/SHP2	0.052	0.017	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0.066	0.02	-10000	0	-10000	0	0
RIT1/GTP	0.02	0.003	-10000	0	-10000	0	0
NT3 (dimer)	-0.11	0.22	-10000	0	-0.46	144	144
RAP1/GDP	-0.027	0.078	0.13	1	-0.2	9	10
KIDINS220/CRKL	0.026	0.019	-10000	0	-0.39	1	1
BDNF (dimer)	-0.004	0.12	-10000	0	-0.43	35	35
ubiquitin-dependent protein catabolic process	-0.025	0.13	-10000	0	-0.24	130	130
Schwann cell development	-0.036	0.032	-10000	0	-10000	0	0
EHD4	0.027	0.004	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.063	0.024	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.029	0.045	-10000	0	-0.25	2	2
RAP1B	0.027	0.006	-10000	0	-10000	0	0
RAP1A	0.027	0.005	-10000	0	-10000	0	0
CDC42/GTP	-0.16	0.22	-10000	0	-0.48	128	128
ABL1	0.027	0.005	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.04	0.008	-10000	0	-10000	0	0
Rap1/GTP	-0.007	0.082	-10000	0	-0.38	8	8
STAT3	0.025	0.058	-10000	0	-0.34	13	13
axon guidance	-0.16	0.2	-10000	0	-0.46	128	128
MAPK3	-0.047	0.12	-10000	0	-0.35	18	18
MAPK1	-0.045	0.11	0.18	7	-0.35	18	25
CDC42/GDP	-0.023	0.1	0.2	16	-0.24	11	27
NTF3	-0.11	0.22	-10000	0	-0.46	144	144
NTF4	0.025	0.034	-10000	0	-0.41	3	3
NGF (dimer)/TRKA/FAIM	-0.027	0.12	-10000	0	-0.24	122	122
PI3K	0.027	0.03	-10000	0	-0.33	2	2
FRS3	0.027	0.006	-10000	0	-10000	0	0
FAIM	0.023	0.011	-10000	0	-10000	0	0
GAB1	0.027	0.006	-10000	0	-10000	0	0
RASGRF1	-0.047	0.12	0.21	2	-0.3	49	51
SOS1	0.028	0.004	-10000	0	-10000	0	0
MCF2L	-0.14	0.2	-10000	0	-0.36	217	217
RGS19	0.027	0.006	-10000	0	-10000	0	0
CDC42	0.027	0.005	-10000	0	-10000	0	0
RAS family/GTP	0.029	0.07	-10000	0	-0.43	1	1
Rac1/GDP	-0.024	0.095	0.19	11	-0.24	11	22
NGF (dimer)/TRKA/GRIT	-0.036	0.12	-10000	0	-0.24	132	132
neuron projection morphogenesis	0.005	0.12	-10000	0	-0.7	6	6
NGF (dimer)/TRKA/NEDD4-2	-0.024	0.13	-10000	0	-0.24	130	130
MAP2K1	0.022	0.037	0.36	1	-10000	0	1
NGFR	0.005	0.098	-10000	0	-0.42	26	26
NGF (dimer)/TRKA/GIPC/GAIP	-0.014	0.072	-10000	0	-0.29	1	1
RAS family/GTP/PI3K	0.017	0.02	-10000	0	-0.22	2	2
FRS2 family/SHP2/GRB2/SOS1	0.073	0.028	-10000	0	-10000	0	0
NRAS	0.027	0.005	-10000	0	-10000	0	0
GRB2/SOS1	0.04	0.008	-10000	0	-10000	0	0
PRKCI	0.02	0.013	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.026	0.007	-10000	0	-10000	0	0
PRKCZ	0.026	0.022	-10000	0	-0.46	1	1
MAPKKK cascade	-0.027	0.11	-10000	0	-0.46	18	18
RASA1	0.024	0.031	-10000	0	-0.46	2	2
TRKA/c-Abl	0.014	0.086	-10000	0	-0.27	42	42
SQSTM1	0.026	0.007	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.033	0.15	-10000	0	-0.27	123	123
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.009	0.11	-10000	0	-0.32	12	12
MATK	0.017	0.065	-10000	0	-0.4	12	12
NEDD4L	0.025	0.009	-10000	0	-10000	0	0
RAS family/GDP	-0.046	0.059	-10000	0	-0.21	5	5
NGF (dimer)/TRKA	-0.027	0.075	0.21	3	-0.25	24	27
Rac1/GTP	-0.069	0.082	-10000	0	-0.26	29	29
FRS2 family/SHP2/CRK family	0.069	0.033	-10000	0	-10000	0	0

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.027	0.006	-10000	0	-10000	0	0
LAT2	-0.047	0.11	-10000	0	-0.35	25	25
AP1	-0.021	0.14	0.3	1	-0.45	8	9
mol:PIP3	-0.062	0.15	0.35	9	-0.42	24	33
IKBKB	-0.025	0.1	0.22	26	-0.26	12	38
AKT1	-0.029	0.15	0.39	18	-0.38	12	30
IKBKG	-0.026	0.1	0.24	19	-0.26	12	31
MS4A2	0.008	0.091	-10000	0	-0.46	18	18
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
MAP3K1	0.019	0.14	0.25	72	-0.37	8	80
mol:Ca2+	-0.046	0.13	0.28	12	-0.32	23	35
LYN	0.024	0.022	-10000	0	-0.4	1	1
CBLB	-0.043	0.11	-10000	0	-0.34	21	21
SHC1	0.028	0.004	-10000	0	-10000	0	0
RasGAP/p62DOK	0.034	0.069	-10000	0	-0.26	25	25
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	0.025	0.031	-10000	0	-0.46	2	2
PLD2	-0.076	0.14	0.35	8	-0.4	21	29
PTPN13	-0.035	0.13	0.36	1	-0.62	4	5
PTPN11	0.014	0.026	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	-0.004	0.14	0.3	30	-0.33	7	37
SYK	0.024	0.04	-10000	0	-0.48	3	3
GRB2	0.027	0.004	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.068	0.14	-10000	0	-0.42	24	24
LAT	-0.051	0.12	-10000	0	-0.34	29	29
PAK2	0.015	0.15	0.26	77	-0.4	9	86
NFATC2	-0.088	0.19	-10000	0	-0.59	60	60
HRAS	-0.027	0.12	0.25	6	-0.4	16	22
GAB2	0.022	0.038	-10000	0	-0.46	3	3
PLA2G1B	-0.065	0.28	-10000	0	-0.82	60	60
Fc epsilon R1	-0.082	0.18	-10000	0	-0.31	192	192
Antigen/IgE/Fc epsilon R1	-0.072	0.16	-10000	0	-0.28	192	192
mol:GDP	-0.027	0.12	0.25	2	-0.41	15	17
JUN	0.028	0.004	-10000	0	-10000	0	0
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
FOS	-0.034	0.16	-10000	0	-0.46	63	63
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.047	0.12	-10000	0	-0.35	29	29
CHUK	-0.032	0.098	0.25	12	-0.26	12	24
KLRG1	-0.051	0.11	-10000	0	-0.36	26	26
VAV1	-0.049	0.12	-10000	0	-0.36	28	28
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.045	0.11	-10000	0	-0.35	24	24
negative regulation of mast cell degranulation	-0.034	0.12	0.24	2	-0.35	23	25
BTK	-0.03	0.11	-10000	0	-0.42	12	12
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.083	0.16	-10000	0	-0.41	48	48
GAB2/PI3K/SHP2	-0.062	0.11	-10000	0	-0.41	12	12
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.056	0.12	-10000	0	-0.39	22	22
RAF1	-0.074	0.3	-10000	0	-0.9	60	60
Fc epsilon R1/FcgammaRIIB/SHIP	-0.054	0.17	-10000	0	-0.28	160	160
FCER1G	0.017	0.064	-10000	0	-0.39	12	12
FCER1A	-0.15	0.24	-10000	0	-0.47	180	180
Antigen/IgE/Fc epsilon R1/Fyn	-0.059	0.16	-10000	0	-0.27	177	177
MAPK3	-0.067	0.28	-10000	0	-0.83	60	60
MAPK1	-0.067	0.28	-10000	0	-0.83	60	60
NFKB1	0.027	0.005	-10000	0	-10000	0	0
MAPK8	0.008	0.14	-10000	0	-0.62	14	14
DUSP1	0.005	0.1	-10000	0	-0.46	23	23
NF-kappa-B/RelA	-0.013	0.061	0.14	1	-10000	0	1
actin cytoskeleton reorganization	-0.032	0.12	0.37	1	-0.6	4	5
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.023	0.11	-10000	0	-0.39	11	11
FER	-0.046	0.11	-10000	0	-0.34	27	27
RELA	0.027	0.006	-10000	0	-10000	0	0
ITK	-0.021	0.073	-10000	0	-0.29	24	24
SOS1	0.028	0.004	-10000	0	-10000	0	0
PLCG1	-0.028	0.13	0.3	7	-0.42	15	22
cytokine secretion	-0.013	0.042	-10000	0	-10000	0	0
SPHK1	-0.05	0.12	-10000	0	-0.35	31	31
PTK2	-0.033	0.13	0.38	1	-0.64	4	5
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.063	0.15	-10000	0	-0.44	22	22
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	-0.059	0.15	0.34	9	-0.42	21	30
MAP2K2	-0.073	0.28	-10000	0	-0.84	60	60
MAP2K1	-0.072	0.28	-10000	0	-0.84	60	60
MAP2K7	0.027	0.004	-10000	0	-10000	0	0
KLRG1/SHP2	-0.039	0.12	0.22	9	-0.34	25	34
MAP2K4	0.003	0.18	-10000	0	-0.83	22	22
Fc epsilon R1/FcgammaRIIB	-0.065	0.18	-10000	0	-0.29	186	186
mol:Choline	-0.075	0.14	0.35	8	-0.39	21	29
SHC/Grb2/SOS1	-0.013	0.13	0.25	1	-0.41	12	13
FYN	0.027	0.019	-10000	0	-0.39	1	1
DOK1	0.027	0.018	-10000	0	-0.39	1	1
PXN	-0.031	0.12	0.36	1	-0.58	4	5
HCLS1	-0.044	0.11	0.18	1	-0.35	24	25
PRKCB	-0.044	0.12	0.28	12	-0.34	15	27
FCGR2B	0.021	0.057	-10000	0	-0.46	7	7
IGHE	-0.001	0.007	-10000	0	-10000	0	0
KLRG1/SHIP	-0.034	0.12	0.24	2	-0.36	23	25
LCP2	0.024	0.032	-10000	0	-0.39	3	3
PLA2G4A	-0.056	0.13	-10000	0	-0.37	38	38
RASA1	0.024	0.031	-10000	0	-0.46	2	2
mol:Phosphatidic acid	-0.075	0.14	0.35	8	-0.39	21	29
IKK complex	-0.012	0.091	0.2	33	-0.22	3	36
WIPF1	0.023	0.037	-10000	0	-0.39	4	4

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.026	0.02	-9999	-0.4	1	1
EGFR	0.02	0.044	-9999	-0.46	4	4
EGF/EGFR	-0.009	0.11	-9999	-0.24	86	86
EGF/EGFR dimer/SHC/GRB2/SOS1	0.011	0.12	-9999	-0.24	85	85
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.024	0.032	-9999	-0.39	3	3
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.067	0.19	-9999	-0.46	98	98
EGF/EGFR dimer/SHC	-0.012	0.13	-9999	-0.28	87	87
mol:GDP	0.006	0.12	-9999	-0.24	85	85
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.022	0.048	-9999	-0.46	5	5
GRB2/SOS1	0.04	0.008	-9999	-10000	0	0
HRAS/GTP	-0.006	0.1	-9999	-0.33	2	2
SHC1	0.028	0.004	-9999	-10000	0	0
HRAS/GDP	0.006	0.11	-9999	-0.44	1	1
FRAP1	-0.046	0.084	-9999	-0.23	85	85
EGF/EGFR dimer	-0.029	0.14	-9999	-0.33	88	88
SOS1	0.028	0.004	-9999	-10000	0	0
GRB2	0.027	0.004	-9999	-10000	0	0
ETA receptor/Endothelin-1	0.033	0.045	-9999	-0.31	8	8

×

LPA4-mediated signaling events

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
ADCY4	-0.005	0.012	-10000	0	-0.28	1	1
ADCY5	-0.063	0.11	-10000	0	-0.28	111	111
ADCY6	-0.01	0.04	-10000	0	-0.28	11	11
ADCY7	-0.005	0.012	-10000	0	-0.28	1	1
ADCY1	-0.013	0.044	-10000	0	-0.23	20	20
ADCY2	-0.087	0.13	-10000	0	-0.28	155	155
ADCY3	-0.005	0.012	-10000	0	-0.28	1	1
ADCY8	-0.013	0.034	-10000	0	-0.23	12	12
PRKCE	0.007	0.015	-10000	0	-0.33	1	1
ADCY9	-0.006	0.021	-10000	0	-0.28	3	3
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	-0.008	0.11	0.22	35	-0.27	5	40

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.006	0.089	-10000	0	-0.39	25	25
GNB1/GNG2	-0.042	0.067	-10000	0	-0.18	63	63
AKT1	-0.015	0.11	0.21	9	-0.3	14	23
EGF	-0.067	0.19	-10000	0	-0.46	98	98
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.017	0.078	0.27	9	-10000	0	9
mol:Ca2+	-0.028	0.14	0.25	3	-0.3	66	69
LYN	0.013	0.074	0.27	7	-0.33	1	8
RhoA/GTP	-0.013	0.057	0.11	1	-0.14	1	2
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.035	0.15	0.28	5	-0.34	71	76
GNG2	0.026	0.007	-10000	0	-10000	0	0
ARRB2	0.027	0.006	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.012	0.12	0.27	1	-0.54	18	19
G beta5/gamma2	-0.053	0.088	-10000	0	-0.25	60	60
PRKCH	-0.034	0.15	0.29	11	-0.35	67	78
DNM1	0	0.1	-10000	0	-0.39	34	34
TXA2/TP beta/beta Arrestin3	0.005	0.046	-10000	0	-0.49	2	2
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	0.018	0.059	-10000	0	-0.42	9	9
G12 family/GTP	-0.043	0.12	-10000	0	-0.3	66	66
ADRBK1	0.026	0.008	-10000	0	-10000	0	0
ADRBK2	0.026	0.019	-10000	0	-0.39	1	1
RhoA/GTP/ROCK1	0.032	0.014	-10000	0	-10000	0	0
mol:GDP	0.01	0.099	0.33	14	-0.21	2	16
mol:NADP	0.021	0.045	-10000	0	-0.39	6	6
RAB11A	0.027	0.004	-10000	0	-10000	0	0
PRKG1	0.001	0.11	-10000	0	-0.44	28	28
mol:IP3	-0.04	0.16	0.3	1	-0.37	69	70
cell morphogenesis	0.031	0.014	-10000	0	-10000	0	0
PLCB2	-0.063	0.21	-10000	0	-0.5	69	69
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.008	0.098	0.27	8	-0.33	4	12
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.014	0.075	0.27	9	-10000	0	9
RHOA	0.025	0.009	-10000	0	-10000	0	0
PTGIR	0.011	0.08	-10000	0	-0.39	20	20
PRKCB1	-0.041	0.16	0.28	1	-0.37	73	74
GNAQ	0.027	0.005	-10000	0	-10000	0	0
mol:L-citrulline	0.021	0.045	-10000	0	-0.39	6	6
TXA2/TXA2-R family	-0.064	0.22	0.33	1	-0.51	76	77
LCK	0.013	0.082	0.27	9	-10000	0	9
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.014	0.072	-10000	0	-0.29	12	12
TXA2-R family/G12 family/GDP/G beta/gamma	0.014	0.089	0.26	1	-0.43	17	18
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.019	0.072	-10000	0	-0.28	12	12
MAPK14	-0.018	0.11	0.2	13	-0.23	32	45
TGM2/GTP	-0.056	0.17	-10000	0	-0.42	61	61
MAPK11	-0.018	0.11	0.22	17	-0.24	32	49
ARHGEF1	-0.016	0.081	0.16	6	-0.18	28	34
GNAI2	0.024	0.009	-10000	0	-10000	0	0
JNK cascade	-0.042	0.17	0.28	2	-0.38	76	78
RAB11/GDP	0.027	0.004	-10000	0	-10000	0	0
ICAM1	-0.028	0.13	0.23	3	-0.28	80	83
cAMP biosynthetic process	-0.039	0.15	0.27	2	-0.35	62	64
Gq family/GTP/EBP50	-0.008	0.088	0.24	7	-0.36	9	16
actin cytoskeleton reorganization	0.031	0.014	-10000	0	-10000	0	0
SRC	0.015	0.075	0.27	9	-10000	0	9
GNB5	0.027	0.004	-10000	0	-10000	0	0
GNB1	0.027	0.006	-10000	0	-10000	0	0
EGF/EGFR	0.007	0.098	0.23	30	-0.28	3	33
VCAM1	-0.035	0.14	0.23	3	-0.31	88	91
TP beta/Gq family/GDP/G beta5/gamma2	-0.012	0.12	0.27	1	-0.54	18	19
platelet activation	-0.023	0.14	0.27	14	-0.3	62	76
PGI2/IP	0.009	0.056	-10000	0	-0.27	20	20
PRKACA	0.011	0.039	-10000	0	-0.24	5	5
Gq family/GDP/G beta5/gamma2	-0.007	0.1	0.28	1	-0.45	18	19
TXA2/TP beta/beta Arrestin2	0.002	0.048	-10000	0	-0.32	2	2
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.007	0.066	-10000	0	-0.29	16	16
mol:DAG	-0.047	0.18	0.31	1	-0.42	73	74
EGFR	0.02	0.044	-10000	0	-0.46	4	4
TXA2/TP alpha	-0.057	0.2	0.35	1	-0.47	63	64
Gq family/GTP	-0.023	0.089	0.28	2	-0.22	71	73
YES1	0.015	0.071	0.27	7	-10000	0	7
GNAI2/GTP	0.006	0.06	-10000	0	-0.26	11	11
PGD2/DP	0.014	0.042	-10000	0	-0.3	9	9
SLC9A3R1	0.024	0.043	-10000	0	-0.46	4	4
FYN	0.016	0.076	0.27	7	-0.29	1	8
mol:NO	0.021	0.045	-10000	0	-0.39	6	6
GNA15	0.025	0.031	-10000	0	-0.46	2	2
PGK/cGMP	0.015	0.074	-10000	0	-0.26	34	34
RhoA/GDP	0.024	0.009	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0.021	0.091	-10000	0	-0.34	16	16
NOS3	0.021	0.045	-10000	0	-0.39	6	6
RAC1	0.026	0.007	-10000	0	-10000	0	0
PRKCA	-0.037	0.15	0.27	2	-0.35	70	72
PRKCB	-0.039	0.16	0.3	4	-0.35	72	76
PRKCE	-0.036	0.16	0.28	2	-0.35	69	71
PRKCD	-0.045	0.16	0.27	1	-0.37	78	79
PRKCG	-0.05	0.17	0.27	2	-0.39	79	81
muscle contraction	-0.057	0.2	0.31	2	-0.47	74	76
PRKCZ	-0.037	0.15	0.27	2	-0.34	73	75
ARR3	-0.012	0.016	-10000	0	-10000	0	0
TXA2/TP beta	0.018	0.072	-10000	0	-0.28	11	11
PRKCQ	-0.042	0.16	0.28	1	-0.36	72	73
MAPKKK cascade	-0.053	0.19	0.32	1	-0.44	70	71
SELE	-0.042	0.16	0.23	3	-0.38	76	79
TP beta/GNAI2/GDP/G beta/gamma	0.028	0.075	-10000	0	-0.29	12	12
ROCK1	0.026	0.007	-10000	0	-10000	0	0
GNA14	-0.041	0.17	-10000	0	-0.46	71	71
chemotaxis	-0.077	0.25	-10000	0	-0.59	78	78
GNA12	0.025	0.02	-10000	0	-0.39	1	1
GNA13	0.028	0.003	-10000	0	-10000	0	0
GNA11	0.024	0.038	-10000	0	-0.46	3	3
Rac1/GTP	0.019	0.005	-10000	0	-10000	0	0

×

IGF1 pathway

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
NCK2	0.028	0.003	-10000	0	-10000	0	0
PTK2	0.023	0.011	-10000	0	-10000	0	0
CRKL	-0.022	0.092	-10000	0	-0.24	74	74
GRB2/SOS1/SHC	0.054	0.013	-10000	0	-10000	0	0
HRAS	0.026	0.02	-10000	0	-0.4	1	1
IRS1/Crk	-0.016	0.097	-10000	0	-0.24	78	78
IGF-1R heterotetramer/IGF1/PTP1B	0.003	0.12	-10000	0	-0.27	74	74
AKT1	0.008	0.11	0.23	15	-0.4	2	17
BAD	0.005	0.1	0.23	13	-0.38	2	15
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.024	0.094	-10000	0	-0.24	78	78
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.011	0.1	0.21	1	-0.24	78	79
RAF1	-0.008	0.16	0.28	10	-0.46	33	43
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.018	0.11	-10000	0	-0.23	68	68
YWHAZ	0.024	0.01	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.012	0.11	-10000	0	-0.26	78	78
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
RPS6KB1	0.012	0.12	0.23	19	-0.4	2	21
GNB2L1	0.026	0.007	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.006	0.13	0.26	13	-0.37	26	39
PXN	0.028	0.002	-10000	0	-10000	0	0
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.04	0.008	-10000	0	-10000	0	0
HRAS/GTP	-0.005	0.087	-10000	0	-0.38	2	2
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.033	0.11	-10000	0	-0.27	1	1
IGF-1R heterotetramer	0.013	0.039	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	0.005	0.11	-10000	0	-0.24	76	76
Crk/p130 Cas/Paxillin	0.015	0.1	-10000	0	-0.36	1	1
IGF1R	0.013	0.039	-10000	0	-10000	0	0
IGF1	-0.052	0.19	-10000	0	-0.47	85	85
IRS2/Crk	-0.014	0.094	-10000	0	-0.36	3	3
PI3K	0.009	0.094	-10000	0	-0.24	50	50
apoptosis	-0.027	0.096	0.32	1	-0.26	16	17
HRAS/GDP	0.019	0.014	-10000	0	-0.28	1	1
PRKCD	-0.035	0.13	-10000	0	-0.34	72	72
RAF1/14-3-3 E	0.002	0.15	0.28	12	-0.4	30	42
BAD/14-3-3	0.027	0.1	0.27	16	-0.34	1	17
PRKCZ	0.007	0.11	0.23	15	-0.4	2	17
Crk/p130 Cas/Paxillin/FAK1	0.021	0.084	-10000	0	-0.31	1	1
PTPN1	0.027	0.006	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.037	0.14	-10000	0	-0.35	78	78
BCAR1	0.027	0.006	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.017	0.11	-10000	0	-0.24	69	69
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.028	0.004	-10000	0	-10000	0	0
IRS1/NCK2	-0.008	0.1	-10000	0	-0.24	76	76
GRB10	0.026	0.007	-10000	0	-10000	0	0
PTPN11	-0.023	0.095	-10000	0	-0.24	78	78
IRS1	-0.025	0.1	-10000	0	-0.26	78	78
IRS2	-0.022	0.095	-10000	0	-0.24	75	75
IGF-1R heterotetramer/IGF1	-0.02	0.14	-10000	0	-0.35	80	80
GRB2	0.027	0.004	-10000	0	-10000	0	0
PDPK1	0.021	0.12	0.26	12	-0.41	2	14
YWHAE	0.027	0.006	-10000	0	-10000	0	0
PRKD1	-0.039	0.13	-10000	0	-0.35	70	70
SHC1	0.028	0.004	-10000	0	-10000	0	0

×

IL12-mediated signaling events

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
IL12/IL12R/TYK2/JAK2/SOCS1	-0.023	0.12	-10000	0	-0.35	24	24
TBX21	-0.081	0.32	-10000	0	-1	38	38
B2M	0.021	0.019	-10000	0	-10000	0	0
TYK2	0.019	0.037	-10000	0	-0.41	1	1
IL12RB1	-0.009	0.12	-10000	0	-0.42	37	37
GADD45B	-0.036	0.23	-10000	0	-0.83	10	10
IL12RB2	-0.07	0.17	-10000	0	-0.39	113	113
GADD45G	-0.038	0.24	-10000	0	-0.8	18	18
natural killer cell activation	0.002	0.019	0.039	5	-0.043	23	28
RELB	0.024	0.037	-10000	0	-0.39	4	4
RELA	0.027	0.006	-10000	0	-10000	0	0
IL18	0.013	0.075	-10000	0	-0.46	12	12
IL2RA	-0.011	0.12	-10000	0	-0.39	47	47
IFNG	-0.055	0.16	-10000	0	-0.39	97	97
STAT3 (dimer)	-0.044	0.24	-10000	0	-0.7	33	33
HLA-DRB5	-0.002	0.007	-10000	0	-0.022	48	48
FASLG	-0.086	0.34	0.55	1	-1	42	43
NF kappa B2 p52/RelB	-0.055	0.28	-10000	0	-0.86	32	32
CD4	0.019	0.033	-10000	0	-0.43	2	2
SOCS1	0.003	0.097	-10000	0	-0.39	30	30
EntrezGene:6955	-0.004	0.012	-10000	0	-0.026	96	96
CD3D	0.002	0.079	-10000	0	-0.43	15	15
CD3E	0.005	0.073	-10000	0	-0.42	13	13
CD3G	-0.009	0.11	-10000	0	-0.44	28	28
IL12Rbeta2/JAK2	-0.035	0.13	-10000	0	-0.28	103	103
CCL3	-0.072	0.29	-10000	0	-0.94	32	32
CCL4	-0.069	0.29	-10000	0	-0.95	29	29
HLA-A	-0.002	0.008	-10000	0	-0.023	49	49
IL18/IL18R	0.037	0.095	-10000	0	-0.28	30	30
NOS2	-0.073	0.3	-10000	0	-0.93	32	32
IL12/IL12R/TYK2/JAK2/SPHK2	-0.015	0.12	0.2	1	-0.33	20	21
IL1R1	-0.063	0.28	0.52	2	-0.88	31	33
IL4	-0.004	0.035	-10000	0	-10000	0	0
JAK2	0.017	0.03	-10000	0	-10000	0	0
EntrezGene:6957	-0.003	0.011	-10000	0	-0.024	96	96
TCR/CD3/MHC I/CD8	-0.063	0.23	-10000	0	-0.61	52	52
RAB7A	-0.005	0.22	0.48	3	-0.71	8	11
lysosomal transport	-0.002	0.22	0.45	5	-0.66	9	14
FOS	-0.16	0.46	-10000	0	-1.2	75	75
STAT4 (dimer)	-0.035	0.26	0.45	2	-0.79	25	27
STAT5A (dimer)	-0.086	0.3	-10000	0	-0.86	43	43
GZMA	-0.086	0.33	-10000	0	-1.1	35	35
GZMB	-0.081	0.31	-10000	0	-0.95	34	34
HLX	0.024	0.037	-10000	0	-0.39	4	4
LCK	-0.075	0.3	-10000	0	-0.93	35	35
TCR/CD3/MHC II/CD4	-0.027	0.13	-10000	0	-0.32	52	52
IL2/IL2R	0.024	0.1	-10000	0	-0.27	33	33
MAPK14	-0.034	0.24	-10000	0	-0.75	20	20
CCR5	-0.07	0.28	-10000	0	-0.94	24	24
IL1B	-0.021	0.13	-10000	0	-0.4	52	52
STAT6	-0.003	0.1	-10000	0	-0.9	2	2
STAT4	0.016	0.066	-10000	0	-0.39	13	13
STAT3	0.028	0.003	-10000	0	-10000	0	0
STAT1	0.009	0.084	-10000	0	-0.39	22	22
NFKB1	0.027	0.005	-10000	0	-10000	0	0
NFKB2	0.027	0.004	-10000	0	-10000	0	0
IL12B	-0.016	0.12	-10000	0	-0.39	44	44
CD8A	-0.011	0.12	-10000	0	-0.43	39	39
CD8B	-0.024	0.14	-10000	0	-0.42	54	54
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.023	0.12	0.34	24	-10000	0	24
IL2RB	0.021	0.053	-10000	0	-0.4	8	8
proteasomal ubiquitin-dependent protein catabolic process	-0.029	0.24	0.42	3	-0.72	25	28
IL2RG	0.014	0.076	-10000	0	-0.4	17	17
IL12	-0.011	0.1	-10000	0	-0.29	53	53
STAT5A	0.028	0.003	-10000	0	-10000	0	0
CD247	0	0.088	-10000	0	-0.41	21	21
IL2	-0.003	0.028	-10000	0	-0.39	1	1
SPHK2	0.027	0.004	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0	0.084	-10000	0	-0.46	15	15
IL12/IL12R/TYK2/JAK2	-0.075	0.31	-10000	0	-0.96	35	35
MAP2K3	-0.035	0.24	-10000	0	-0.71	21	21
RIPK2	0.025	0.009	-10000	0	-10000	0	0
MAP2K6	-0.041	0.25	-10000	0	-0.78	22	22
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.002	0.008	-10000	0	-0.025	54	54
IL18RAP	0.011	0.084	-10000	0	-0.42	18	18
IL12Rbeta1/TYK2	0.009	0.097	-10000	0	-0.3	38	38
EOMES	-0.11	0.28	-10000	0	-0.68	72	72
STAT1 (dimer)	-0.059	0.25	-10000	0	-0.73	35	35
T cell proliferation	-0.008	0.2	0.44	1	-0.58	20	21
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.025	0.032	-10000	0	-0.44	2	2
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.047	0.21	-10000	0	-0.65	19	19
ATF2	-0.026	0.23	-10000	0	-0.72	17	17

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0.029	0.089	-10000	0	-0.51	3	3
HDAC1	0.025	0.005	-10000	0	-10000	0	0
AES	0.027	0.005	-10000	0	-10000	0	0
FBXW11	0.027	0.006	-10000	0	-10000	0	0
DTX1	0.025	0.036	-10000	0	-0.44	3	3
LRP6/FZD1	0.034	0.03	-10000	0	-0.31	3	3
TLE1	0.027	0.005	-10000	0	-10000	0	0
AP1	-0.019	0.095	-10000	0	-0.25	63	63
NCSTN	0.027	0.004	-10000	0	-10000	0	0
ADAM10	0.025	0.031	-10000	0	-0.46	2	2
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.018	0.12	-10000	0	-0.71	11	11
NICD/RBPSUH	0.029	0.086	-10000	0	-0.52	3	3
WIF1	-0.2	0.23	-10000	0	-0.46	221	221
NOTCH1	0.014	0.081	-10000	0	-0.54	3	3
PSENEN	0.027	0.005	-10000	0	-10000	0	0
KREMEN2	-0.12	0.2	-10000	0	-0.39	178	178
DKK1	-0.13	0.2	-10000	0	-0.39	191	191
beta catenin/beta TrCP1	-0.006	0.11	-10000	0	-0.39	18	18
APH1B	0.028	0.004	-10000	0	-10000	0	0
APH1A	0.027	0.005	-10000	0	-10000	0	0
AXIN1	0.006	0.059	-10000	0	-0.4	5	5
CtBP/CBP/TCF1/TLE1/AES	0.016	0.036	-10000	0	-0.32	2	2
PSEN1	0.027	0.006	-10000	0	-10000	0	0
FOS	-0.034	0.16	-10000	0	-0.46	63	63
JUN	0.028	0.004	-10000	0	-10000	0	0
MAP3K7	0.026	0.005	-10000	0	-10000	0	0
CTNNB1	-0.018	0.11	-10000	0	-0.38	25	25
MAPK3	0.028	0.004	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.05	0.14	-10000	0	-0.24	175	175
HNF1A	0.019	0.057	-10000	0	-0.39	10	10
CTBP1	0.025	0.007	-10000	0	-10000	0	0
MYC	0.022	0.041	-10000	0	-0.77	1	1
NKD1	0.012	0.077	-10000	0	-0.39	18	18
FZD1	0.024	0.029	-10000	0	-0.42	2	2
NOTCH1 precursor/Deltex homolog 1	0.03	0.09	-10000	0	-0.58	3	3
apoptosis	-0.019	0.094	-10000	0	-0.25	63	63
Delta 1/NOTCHprecursor	0.028	0.089	-10000	0	-0.51	3	3
DLL1	0.021	0.053	-10000	0	-0.46	6	6
PPARD	0.005	0.15	-10000	0	-0.83	15	15
Gamma Secretase	0.075	0.026	-10000	0	-10000	0	0
APC	-0.009	0.098	-10000	0	-0.39	24	24
DVL1	-0.015	0.079	-10000	0	-0.35	19	19
CSNK2A1	0.027	0.007	-10000	0	-10000	0	0
MAP3K7IP1	-0.001	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.13	0.18	-10000	0	-0.28	284	284
LRP6	0.025	0.023	-10000	0	-0.46	1	1
CSNK1A1	0.027	0.006	-10000	0	-10000	0	0
NLK	0.013	0.005	-10000	0	-10000	0	0
CCND1	-0.001	0.15	-10000	0	-0.99	9	9
WNT1	0.011	0.051	-10000	0	-0.39	7	7
Axin1/APC/beta catenin	-0.004	0.12	0.26	5	-0.47	18	23
DKK2	0.015	0.074	-10000	0	-0.42	14	14
NOTCH1 precursor/DVL1	-0.004	0.11	-10000	0	-0.54	10	10
GSK3B	0.024	0.009	-10000	0	-10000	0	0
FRAT1	0.027	0.004	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	0.032	0.09	-10000	0	-0.59	3	3
PPP2R5D	0.005	0.079	0.23	4	-0.38	13	17
MAPK1	0.027	0.005	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.075	0.15	-10000	0	-0.26	190	190
RBPJ	0.026	0.007	-10000	0	-10000	0	0
CREBBP	0.029	0.006	-10000	0	-10000	0	0

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	-0.042	0.16	-10000	0	-0.46	64	64
NFATC2	-0.027	0.19	-10000	0	-0.59	30	30
NFATC3	-0.003	0.068	-10000	0	-0.33	1	1
CD40LG	-0.25	0.31	-10000	0	-0.84	62	62
ITCH	0.007	0.074	-10000	0	-10000	0	0
CBLB	0.004	0.076	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.2	0.31	-10000	0	-0.83	68	68
JUNB	0.028	0.003	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0.006	0.094	-10000	0	-0.26	51	51
T cell anergy	-0.008	0.14	0.31	5	-0.39	47	52
TLE4	-0.017	0.14	-10000	0	-0.55	12	12
Jun/NFAT1-c-4/p21SNFT	-0.092	0.23	-10000	0	-0.84	20	20
AP-1/NFAT1-c-4	-0.24	0.32	-10000	0	-0.92	48	48
IKZF1	-0.02	0.15	-10000	0	-0.64	14	14
T-helper 2 cell differentiation	-0.067	0.21	-10000	0	-0.68	32	32
AP-1/NFAT1	-0.086	0.17	-10000	0	-0.5	37	37
CALM1	0.016	0.06	-10000	0	-10000	0	0
EGR2	-0.064	0.26	-10000	0	-1.4	14	14
EGR3	-0.056	0.23	-10000	0	-1	17	17
NFAT1/FOXP3	-0.054	0.21	-10000	0	-0.52	53	53
EGR1	0.004	0.1	-10000	0	-0.46	22	22
JUN	-0.02	0.042	-10000	0	-0.2	1	1
EGR4	-0.021	0.13	-10000	0	-0.4	57	57
mol:Ca2+	-0.009	0.054	-10000	0	-0.24	2	2
GBP3	-0.031	0.17	-10000	0	-0.62	26	26
FOSL1	0.018	0.059	-10000	0	-0.4	10	10
NFAT1-c-4/MAF/IRF4	-0.051	0.22	-10000	0	-0.83	21	21
DGKA	-0.016	0.13	-10000	0	-0.52	10	10
CREM	0.027	0.005	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.14	0.25	-10000	0	-0.92	20	20
CTLA4	-0.081	0.22	-10000	0	-0.56	64	64
NFAT1-c-4 (dimer)/EGR1	-0.061	0.23	-10000	0	-0.91	19	19
NFAT1-c-4 (dimer)/EGR4	-0.073	0.23	-10000	0	-0.86	19	19
FOS	-0.079	0.16	-10000	0	-0.48	63	63
IFNG	-0.11	0.23	-10000	0	-0.74	27	27
T cell activation	-0.091	0.16	-10000	0	-0.64	10	10
MAF	0.022	0.048	-10000	0	-0.46	5	5
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.04	0.15	0.64	18	-10000	0	18
TNF	-0.095	0.22	-10000	0	-0.8	26	26
FASLG	-0.12	0.35	-10000	0	-1.3	30	30
TBX21	-0.012	0.11	-10000	0	-0.44	29	29
BATF3	0.024	0.037	-10000	0	-0.39	4	4
PRKCQ	0.014	0.072	-10000	0	-0.45	11	11
PTPN1	-0.016	0.13	-10000	0	-0.5	12	12
NFAT1-c-4/ICER1	-0.052	0.21	-10000	0	-0.87	17	17
GATA3	0.011	0.083	-10000	0	-0.4	20	20
T-helper 1 cell differentiation	-0.11	0.22	-10000	0	-0.73	27	27
IL2RA	-0.18	0.28	-10000	0	-0.75	68	68
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.017	0.13	-10000	0	-0.55	8	8
E2F1	0.014	0.08	-10000	0	-0.38	20	20
PPARG	-0.13	0.23	-10000	0	-0.46	166	166
SLC3A2	-0.016	0.13	-10000	0	-0.5	12	12
IRF4	-0.001	0.11	-10000	0	-0.4	33	33
PTGS2	-0.25	0.3	-10000	0	-0.82	68	68
CSF2	-0.31	0.32	-10000	0	-0.81	89	89
JunB/Fra1/NFAT1-c-4	-0.038	0.21	-10000	0	-0.85	16	16
IL4	-0.07	0.22	-10000	0	-0.72	32	32
IL5	-0.23	0.28	-10000	0	-0.82	47	47
IL2	-0.092	0.16	-10000	0	-0.65	10	10
IL3	-0.054	0.15	-10000	0	-0.7	21	21
RNF128	-0.032	0.18	-10000	0	-0.53	58	58
NFATC1	-0.04	0.15	-10000	0	-0.64	18	18
CDK4	0.039	0.12	0.63	3	-10000	0	3
PTPRK	-0.015	0.13	-10000	0	-0.54	8	8
IL8	-0.26	0.3	-10000	0	-0.81	68	68
POU2F1	0.028	0.004	-10000	0	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	-0.008	0.021	-10000	0	-0.28	3	3
SNTA1	0.026	0.008	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	-0.009	0.027	-10000	0	-0.26	5	5
MAPK12	-0.017	0.066	0.18	2	-0.24	38	40
CCND1	-0.001	0.061	-10000	0	-0.45	7	7
p38 gamma/SNTA1	0.006	0.074	0.23	9	-0.24	25	34
MAP2K3	0.027	0.006	-10000	0	-10000	0	0
PKN1	0.026	0.026	-10000	0	-0.39	2	2
G2/M transition checkpoint	-0.016	0.065	0.18	2	-0.24	38	40
MAP2K6	-0.01	0.059	-10000	0	-0.27	25	25
MAPT	-0.14	0.16	0.2	2	-0.3	232	234
MAPK13	0.012	0.027	-10000	0	-0.33	3	3
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.007	0.011	-10000	0	-0.16	2	2

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	-0.004	0.006	-10000	0	-10000	0	0
RAS family/GTP	-0.009	0.084	-10000	0	-0.3	3	3
NFATC4	-0.024	0.071	0.27	6	-0.34	3	9
ERBB2IP	0.027	0.007	-10000	0	-10000	0	0
HSP90 (dimer)	0.026	0.007	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.017	0.075	-10000	0	-0.26	4	4
JUN	-0.008	0.075	0.2	8	-0.38	3	11
HRAS	0.025	0.02	-10000	0	-0.4	1	1
DOCK7	-0.028	0.073	0.29	2	-10000	0	2
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.005	0.093	-10000	0	-0.24	27	27
AKT1	0.005	0.006	-10000	0	-10000	0	0
BAD	-0.004	0.004	-10000	0	-10000	0	0
MAPK10	-0.017	0.066	0.2	12	-0.25	3	15
mol:GTP	-0.001	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.017	0.08	-10000	0	-0.28	4	4
RAF1	-0.022	0.094	0.26	6	-0.32	3	9
ErbB2/ErbB3/neuregulin 2	-0.13	0.15	-10000	0	-0.27	265	265
STAT3	0.015	0.12	-10000	0	-0.81	10	10
cell migration	-0.009	0.066	0.23	12	-0.22	1	13
mol:PI-3-4-5-P3	-0.001	0.001	-10000	0	-10000	0	0
cell proliferation	-0.18	0.29	-10000	0	-0.6	136	136
FOS	-0.12	0.22	0.34	5	-0.39	166	171
NRAS	0.026	0.005	-10000	0	-10000	0	0
mol:Ca2+	-0.017	0.075	-10000	0	-0.26	4	4
MAPK3	-0.14	0.24	-10000	0	-0.5	124	124
MAPK1	-0.14	0.24	0.3	2	-0.5	123	125
JAK2	-0.027	0.068	-10000	0	-10000	0	0
NF2	0.008	0.041	-10000	0	-0.63	2	2
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.006	0.062	-10000	0	-0.26	11	11
NRG1	-0.036	0.15	-10000	0	-0.39	74	74
GRB2/SOS1	0.039	0.008	-10000	0	-10000	0	0
MAPK8	-0.01	0.078	0.22	7	-0.28	14	21
MAPK9	-0.011	0.057	0.2	12	-10000	0	12
ERBB2	-0.019	0.007	-10000	0	-10000	0	0
ERBB3	0.019	0.061	-10000	0	-0.46	8	8
SHC1	0.027	0.004	-10000	0	-10000	0	0
RAC1	0.026	0.007	-10000	0	-10000	0	0
apoptosis	0.009	0.032	-10000	0	-0.17	13	13
STAT3 (dimer)	0.016	0.12	-10000	0	-0.8	10	10
RNF41	-0.007	0.007	-10000	0	-10000	0	0
FRAP1	-0.002	0.003	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.021	0.049	-10000	0	-10000	0	0
ErbB2/ErbB2/HSP90 (dimer)	0	0.02	-10000	0	-10000	0	0
CHRNA1	-0.18	0.29	0.28	2	-0.62	135	137
myelination	-0.014	0.086	0.3	15	-0.31	3	18
PPP3CB	-0.026	0.07	0.28	2	-10000	0	2
KRAS	0.026	0.007	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0.02	0.069	-10000	0	-10000	0	0
NRG2	-0.24	0.24	-10000	0	-0.46	274	274
mol:GDP	-0.006	0.062	-10000	0	-0.26	11	11
SOS1	0.027	0.004	-10000	0	-10000	0	0
MAP2K2	-0.038	0.11	0.26	6	-0.34	3	9
SRC	0.026	0.007	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.001	-10000	0	-10000	0	0
PTPN11	-0.027	0.074	0.29	2	-10000	0	2
MAP2K1	-0.12	0.23	-10000	0	-0.6	39	39
heart morphogenesis	-0.017	0.075	-10000	0	-0.26	4	4
RAS family/GDP	0.009	0.081	-10000	0	-0.34	1	1
GRB2	0.027	0.004	-10000	0	-10000	0	0
PRKACA	0.011	0.043	-10000	0	-0.66	2	2
CHRNE	0.004	0.022	0.083	2	-0.14	5	7
HSP90AA1	0.026	0.007	-10000	0	-10000	0	0
activation of caspase activity	-0.005	0.006	-10000	0	-10000	0	0
nervous system development	-0.017	0.075	-10000	0	-0.26	4	4
CDC42	0.027	0.005	-10000	0	-10000	0	0

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.029	0.034	-10000	0	-0.28	5	5
ARNO/beta Arrestin1-2	0.01	0.12	-10000	0	-0.76	9	9
EGFR	0.02	0.044	-10000	0	-0.46	4	4
EPHA2	0.021	0.053	-10000	0	-0.46	6	6
USP6	0.026	0.019	-10000	0	-0.39	1	1
IQSEC1	0.025	0.009	-10000	0	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.029	0.14	-10000	0	-0.34	88	88
ARRB2	0.01	0.003	-10000	0	-10000	0	0
mol:GTP	0.035	0.051	0.12	77	-0.15	4	81
ARRB1	0.024	0.031	-10000	0	-0.46	2	2
FBXO8	0.027	0.006	-10000	0	-10000	0	0
TSHR	0.01	0.064	-10000	0	-0.39	12	12
EGF	-0.067	0.19	-10000	0	-0.46	98	98
somatostatin receptor activity	0	0	0.001	26	-0.001	18	44
ARAP2	0.022	0.048	-10000	0	-0.46	5	5
mol:GDP	-0.006	0.094	0.18	12	-0.3	21	33
mol:PI-3-4-5-P3	0	0	0.001	14	-0.001	8	22
ITGA2B	-0.013	0.12	-10000	0	-0.39	51	51
ARF6	0.026	0.007	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.053	0.041	-10000	0	-0.26	4	4
ADAP1	0.025	0.023	-10000	0	-0.46	1	1
KIF13B	0.022	0.044	-10000	0	-0.46	4	4
HGF/MET	0.02	0.079	-10000	0	-0.31	28	28
PXN	0.028	0.002	-10000	0	-10000	0	0
ARF6/GTP	-0.01	0.11	0.21	22	-0.3	18	40
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.016	0.12	-10000	0	-0.28	88	88
ADRB2	-0.009	0.13	-10000	0	-0.46	37	37
receptor agonist activity	0	0	0	23	0	10	33
actin filament binding	0	0	0	24	-0.001	18	42
SRC	0.026	0.007	-10000	0	-10000	0	0
ITGB3	0.01	0.087	-10000	0	-0.41	21	21
GNAQ	0.027	0.005	-10000	0	-10000	0	0
EFA6/PI-4-5-P2	0	0.001	0.001	38	-0.001	10	48
ARF6/GDP	0.034	0.13	0.24	29	-0.52	12	41
ARF6/GDP/GULP/ACAP1	-0.044	0.16	0.23	2	-0.36	46	48
alphaIIb/beta3 Integrin/paxillin/GIT1	0.032	0.1	-10000	0	-0.22	67	67
ACAP1	0.017	0.063	-10000	0	-0.39	12	12
ACAP2	0.02	0.013	-10000	0	-10000	0	0
LHCGR/beta Arrestin2	0.016	0.015	-10000	0	-10000	0	0
EFNA1	0.027	0.004	-10000	0	-10000	0	0
HGF	0.006	0.095	-10000	0	-0.44	22	22
CYTH3	0.007	0.002	-10000	0	-10000	0	0
CYTH2	0.003	0.13	-10000	0	-0.98	9	9
NCK1	0.023	0.011	-10000	0	-10000	0	0
fibronectin binding	0	0	0	18	0	12	30
endosomal lumen acidification	0	0	0	42	-0.001	15	57
microtubule-based process	0	0	-10000	0	-10000	0	0
GULP1	-0.11	0.22	-10000	0	-0.46	145	145
GNAQ/ARNO	0.019	0.12	-10000	0	-0.91	9	9
mol:Phosphatidic acid	0	0	0	2	-10000	0	2
PIP3-E	0	0	0	12	0	1	13
MET	0.022	0.048	-10000	0	-0.41	6	6
GNA14	-0.041	0.17	-10000	0	-0.46	71	71
GNA15	0.025	0.031	-10000	0	-0.46	2	2
GIT1	0.028	0.003	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	0.001	33	-0.001	14	47
GNA11	0.024	0.038	-10000	0	-0.46	3	3
LHCGR	-0.011	0.016	-10000	0	-10000	0	0
AGTR1	-0.022	0.13	-10000	0	-0.46	41	41
desensitization of G-protein coupled receptor protein signaling pathway	0.016	0.015	-10000	0	-10000	0	0
IPCEF1/ARNO	-0.015	0.14	-10000	0	-0.8	9	9
alphaIIb/beta3 Integrin	-0.003	0.11	-10000	0	-0.29	69	69

×

Ephrin B reverse signaling

Figure S39. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S39. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.026	0.022	-10000	0	-0.46	1	1
EPHB2	-0.083	0.18	-10000	0	-0.39	137	137
EFNB1	-0.004	0.069	-10000	0	-0.27	32	32
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.024	0.12	-10000	0	-0.36	14	14
Ephrin B2/EPHB1-2	-0.025	0.11	-10000	0	-0.21	124	124
neuron projection morphogenesis	-0.033	0.11	-10000	0	-0.35	14	14
Ephrin B1/EPHB1-2/Tiam1	-0.031	0.12	-10000	0	-0.33	23	23
DNM1	0	0.1	-10000	0	-0.38	34	34
cell-cell signaling	0.001	0.004	-10000	0	-10000	0	0
MAP2K4	-0.018	0.11	0.42	1	-0.44	29	30
YES1	-0.025	0.16	-10000	0	-0.69	29	29
Ephrin B1/EPHB1-2/NCK2	-0.027	0.12	-10000	0	-0.37	13	13
PI3K	0.007	0.11	-10000	0	-0.44	23	23
mol:GDP	-0.032	0.12	-10000	0	-0.33	23	23
ITGA2B	-0.013	0.12	-10000	0	-0.39	51	51
endothelial cell proliferation	0.033	0.018	-10000	0	-0.28	1	1
FYN	-0.025	0.16	-10000	0	-0.69	29	29
MAP3K7	-0.021	0.11	0.24	1	-0.48	27	28
FGR	-0.021	0.16	-10000	0	-0.67	30	30
TIAM1	0.021	0.053	-10000	0	-0.46	6	6
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
RGS3	0.027	0.005	-10000	0	-10000	0	0
cell adhesion	-0.019	0.12	-10000	0	-0.44	28	28
LYN	-0.024	0.16	-10000	0	-0.68	29	29
Ephrin B1/EPHB1-2/Src Family Kinases	-0.028	0.15	-10000	0	-0.62	30	30
Ephrin B1/EPHB1-2	-0.02	0.12	-10000	0	-0.53	25	25
SRC	-0.021	0.16	-10000	0	-0.66	30	30
ITGB3	0.01	0.087	-10000	0	-0.41	21	21
EPHB1	0.004	0.09	-10000	0	-0.42	22	22
EPHB4	0.026	0.008	-10000	0	-10000	0	0
RAC1	0.026	0.007	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.034	0.018	-10000	0	-0.28	1	1
alphaIIb/beta3 Integrin	-0.003	0.11	-10000	0	-0.29	69	69
BLK	-0.031	0.16	-10000	0	-0.68	29	29
HCK	-0.02	0.16	-10000	0	-0.67	29	29
regulation of stress fiber formation	0.027	0.12	0.33	18	-10000	0	18
MAPK8	-0.018	0.11	-10000	0	-0.45	28	28
Ephrin B1/EPHB1-2/RGS3	-0.027	0.12	-10000	0	-0.34	18	18
endothelial cell migration	-0.004	0.1	0.22	12	-0.4	24	36
NCK2	0.028	0.003	-10000	0	-10000	0	0
PTPN13	0.016	0.079	-10000	0	-0.57	9	9
regulation of focal adhesion formation	0.027	0.12	0.33	18	-10000	0	18
chemotaxis	0.028	0.12	0.33	18	-10000	0	18
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
Rac1/GTP	-0.028	0.11	-10000	0	-0.36	14	14
angiogenesis	-0.023	0.12	-10000	0	-0.52	28	28
LCK	-0.022	0.16	-10000	0	-0.67	30	30

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.021	0.08	-10000	0	-0.26	13	13
NF kappa B1 p50/RelA/I kappa B alpha	0.009	0.079	0.28	2	-0.34	1	3
AP1	-0.027	0.11	-10000	0	-0.38	14	14
mol:PIP3	-0.012	0.068	-10000	0	-0.42	5	5
AKT1	0.014	0.098	0.27	11	-0.32	1	12
PTK2B	-0.014	0.079	0.19	2	-0.32	12	14
RHOA	-0.022	0.091	0.19	2	-0.3	39	41
PIK3CB	0.023	0.011	-10000	0	-10000	0	0
mol:Ca2+	-0.011	0.06	0.2	4	-0.32	2	6
MAGI3	0.026	0.022	-10000	0	-0.46	1	1
RELA	0.026	0.006	-10000	0	-10000	0	0
apoptosis	-0.011	0.081	-10000	0	-0.28	26	26
HRAS/GDP	0.019	0.014	-10000	0	-0.28	1	1
positive regulation of microtubule depolymerization	-0.092	0.14	0.24	7	-0.33	42	49
NF kappa B1 p50/RelA	-0.014	0.084	-10000	0	-0.37	5	5
endothelial cell migration	-0.032	0.13	-10000	0	-0.35	70	70
ADCY4	-0.006	0.081	-10000	0	-0.35	14	14
ADCY5	-0.041	0.11	-10000	0	-0.4	20	20
ADCY6	-0.009	0.09	-10000	0	-0.4	15	15
ADCY7	-0.004	0.078	-10000	0	-0.36	12	12
ADCY1	-0.008	0.082	0.22	2	-0.36	13	15
ADCY2	-0.058	0.11	0.22	1	-0.38	23	24
ADCY3	-0.006	0.08	-10000	0	-0.36	13	13
ADCY8	-0.012	0.078	-10000	0	-0.35	13	13
ADCY9	-0.006	0.082	-10000	0	-0.37	13	13
GSK3B	0.006	0.097	0.21	43	-0.32	8	51
arachidonic acid secretion	-0.004	0.082	-10000	0	-0.38	12	12
GNG2	0.026	0.007	-10000	0	-10000	0	0
TRIP6	0.016	0.017	-10000	0	-10000	0	0
GNAO1	-0.011	0.077	-10000	0	-0.28	16	16
HRAS	0.026	0.02	-10000	0	-0.4	1	1
NFKBIA	-0.007	0.079	0.28	3	-0.34	4	7
GAB1	0.027	0.006	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	-0.001	0.2	-10000	0	-0.81	29	29
JUN	0.027	0.004	-10000	0	-10000	0	0
LPA/LPA2/NHERF2	0.024	0.038	-10000	0	-0.22	1	1
TIAM1	-0.023	0.23	-10000	0	-0.95	29	29
PIK3R1	0.024	0.031	-10000	0	-0.46	2	2
mol:IP3	-0.011	0.059	0.2	7	-0.32	2	9
PLCB3	0.01	0.034	0.19	5	-10000	0	5
FOS	-0.034	0.16	-10000	0	-0.46	63	63
positive regulation of mitosis	-0.004	0.082	-10000	0	-0.38	12	12
LPA/LPA1-2-3	0.015	0.096	-10000	0	-0.28	25	25
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0	-10000	0	-10000	0	0
BCAR1	0.027	0.006	-10000	0	-10000	0	0
stress fiber formation	0.004	0.074	0.22	3	-0.34	4	7
GNAZ	-0.018	0.09	-10000	0	-0.28	32	32
EGFR/PI3K-beta/Gab1	-0.005	0.074	-10000	0	-0.44	5	5
positive regulation of dendritic cell cytokine production	0.013	0.095	-10000	0	-0.28	25	25
LPA/LPA2/MAGI-3	0.023	0.039	-10000	0	-0.28	1	1
ARHGEF1	0.007	0.088	0.36	3	-0.26	10	13
GNAI2	-0.012	0.077	-10000	0	-0.28	16	16
GNAI3	-0.011	0.078	-10000	0	-0.29	16	16
GNAI1	-0.011	0.079	-10000	0	-0.29	17	17
LPA/LPA3	0.001	0.063	-10000	0	-0.33	12	12
LPA/LPA2	0.009	0.036	-10000	0	-10000	0	0
LPA/LPA1	-0.011	0.094	-10000	0	-0.23	75	75
HB-EGF/EGFR	-0.14	0.12	-10000	0	-0.23	315	315
HBEGF	-0.18	0.13	-10000	0	-0.27	353	353
mol:DAG	-0.011	0.059	0.2	7	-0.32	2	9
cAMP biosynthetic process	-0.015	0.084	0.22	2	-0.36	13	15
NFKB1	0.027	0.005	-10000	0	-10000	0	0
SRC	0.026	0.007	-10000	0	-10000	0	0
GNB1	0.027	0.006	-10000	0	-10000	0	0
LYN	0.001	0.083	0.28	6	-0.34	3	9
GNAQ	0.004	0.046	-10000	0	-0.25	11	11
LPAR2	0.027	0.003	-10000	0	-10000	0	0
LPAR3	0.016	0.074	-10000	0	-0.46	12	12
LPAR1	-0.001	0.089	-10000	0	-0.4	16	16
IL8	-0.11	0.13	0.36	2	-0.41	26	28
PTK2	-0.011	0.078	-10000	0	-0.34	7	7
Rac1/GDP	0.019	0.005	-10000	0	-10000	0	0
CASP3	-0.011	0.082	-10000	0	-0.28	26	26
EGFR	0.02	0.044	-10000	0	-0.46	4	4
PLCG1	-0.012	0.062	0.16	1	-0.28	13	14
PLD2	-0.009	0.083	-10000	0	-0.34	8	8
G12/G13	0.02	0.083	-10000	0	-0.27	15	15
PI3K-beta	-0.015	0.075	-10000	0	-0.34	3	3
cell migration	0.008	0.071	-10000	0	-0.24	26	26
SLC9A3R2	0.027	0.019	-10000	0	-0.39	1	1
PXN	0.003	0.075	0.23	2	-0.34	4	6
HRAS/GTP	-0.006	0.081	-10000	0	-0.4	11	11
RAC1	0.026	0.007	-10000	0	-10000	0	0
MMP9	-0.26	0.19	-10000	0	-0.39	355	355
PRKCE	0.026	0.022	-10000	0	-0.46	1	1
PRKCD	-0.01	0.055	0.2	1	-0.34	1	2
Gi(beta/gamma)	-0.001	0.077	-10000	0	-0.34	11	11
mol:LPA	-0.014	0.044	-10000	0	-0.2	6	6
TRIP6/p130 Cas/FAK1/Paxillin	0.014	0.08	-10000	0	-0.43	2	2
MAPKKK cascade	-0.004	0.082	-10000	0	-0.38	12	12
contractile ring contraction involved in cytokinesis	-0.028	0.1	0.19	2	-0.3	44	46
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.033	0.1	-10000	0	-0.26	81	81
GNA15	0.002	0.052	-10000	0	-0.28	12	12
GNA12	0.025	0.02	-10000	0	-0.39	1	1
GNA13	0.027	0.003	-10000	0	-10000	0	0
MAPT	-0.094	0.14	0.24	7	-0.34	42	49
GNA11	0.002	0.051	-10000	0	-0.26	14	14
Rac1/GTP	-0.002	0.21	-10000	0	-0.86	29	29
MMP2	-0.032	0.13	-10000	0	-0.35	70	70

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.036	0.048	-10000	0	-0.22	7	7
RGS9BP	0.017	0.065	-10000	0	-0.46	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
GRK1	-0.01	0.03	-10000	0	-0.39	2	2
mol:Na +	-0.007	0.09	-10000	0	-0.23	72	72
mol:ADP	-0.022	0.062	-10000	0	-0.28	28	28
GNAT2	0.02	0.017	-10000	0	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.041	0.062	-10000	0	-0.26	20	20
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.028	0.009	-10000	0	-10000	0	0
GRK7	-0.003	0.093	-10000	0	-0.39	28	28
CNGB3	-0.04	0.14	-10000	0	-0.39	73	73
Cone Metarhodopsin II/X-Arrestin	0.014	0.003	-10000	0	-10000	0	0
mol:Ca2+	-0.047	0.13	0.18	34	-0.26	65	99
Cone PDE6	0.052	0.06	-10000	0	-0.25	10	10
Cone Metarhodopsin II	0.01	0.054	-10000	0	-0.21	28	28
Na + (4 Units)	-0.038	0.12	-10000	0	-0.23	136	136
GNAT2/GDP	0.049	0.057	-10000	0	-0.24	11	11
GNB5	0.027	0.004	-10000	0	-10000	0	0
mol:GMP (4 units)	-0.007	0.039	0.18	22	-10000	0	22
Cone Transducin	0.039	0.051	-10000	0	-0.24	7	7
SLC24A2	-0.059	0.16	-10000	0	-0.39	97	97
GNB3/GNGT2	0.027	0.061	-10000	0	-0.28	18	18
GNB3	0.013	0.074	-10000	0	-0.4	16	16
GNAT2/GTP	0.019	0.004	-10000	0	-10000	0	0
CNGA3	0.009	0.028	-10000	0	-0.39	1	1
ARR3	-0.012	0.016	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
cGMP/Cone CNG Channel	-0.007	0.09	-10000	0	-0.23	72	72
mol:Pi	0.04	0.062	-10000	0	-0.26	20	20
Cone CNG Channel	0.012	0.085	-10000	0	-10000	0	0
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	-0.059	0.16	-10000	0	-0.39	97	97
RGS9	0.017	0.065	-10000	0	-0.4	12	12
PDE6C	-0.011	0.017	-10000	0	-10000	0	0
GNGT2	0.026	0.031	-10000	0	-0.46	2	2
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	-0.011	0.016	-10000	0	-10000	0	0

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.034	0.04	-10000	0	-0.29	7	7
alphaV beta3 Integrin	0.029	0.086	-10000	0	-0.27	37	37
PTK2	0.002	0.11	0.32	9	-0.46	5	14
IGF1R	0.027	0.005	-10000	0	-10000	0	0
PI4KB	0.027	0.004	-10000	0	-10000	0	0
MFGE8	0.027	0.004	-10000	0	-10000	0	0
SRC	0.026	0.007	-10000	0	-10000	0	0
CDKN1B	0.005	0.051	-10000	0	-10000	0	0
VEGFA	0.022	0.045	-10000	0	-0.39	6	6
ILK	0.005	0.055	-10000	0	-0.35	2	2
ROCK1	0.026	0.007	-10000	0	-10000	0	0
AKT1	0.001	0.048	-10000	0	-0.41	1	1
PTK2B	0.009	0.064	0.36	1	-0.38	2	3
alphaV/beta3 Integrin/JAM-A	0.02	0.099	-10000	0	-0.29	21	21
CBL	0.025	0.008	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.034	0.066	-10000	0	-0.25	24	24
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.014	0.12	-10000	0	-0.26	73	73
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.011	0.048	-10000	0	-0.32	3	3
alphaV/beta3 Integrin/Syndecan-1	0.039	0.064	-10000	0	-0.25	23	23
PI4KA	0.027	0.006	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.1	0.16	-10000	0	-0.42	47	47
PI4 Kinase	0.039	0.011	-10000	0	-10000	0	0
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.11	0.15	-10000	0	-0.24	271	271
RPS6KB1	-0.12	0.13	-10000	0	-0.4	47	47
TLN1	0.024	0.01	-10000	0	-10000	0	0
MAPK3	-0.058	0.13	-10000	0	-0.51	29	29
GPR124	0.022	0.033	-10000	0	-0.39	3	3
MAPK1	-0.057	0.13	-10000	0	-0.5	29	29
PXN	0.028	0.002	-10000	0	-10000	0	0
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
alphaV/beta3 Integrin/Tumstatin	0.004	0.11	-10000	0	-0.26	74	74
cell adhesion	0.028	0.06	-10000	0	-0.29	7	7
ANGPTL3	-0.003	0.037	-10000	0	-0.39	3	3
VEGFR2 homodimer/VEGFA homodimer/Src	0.045	0.039	-10000	0	-0.24	7	7
IGF-1R heterotetramer	0.027	0.005	-10000	0	-10000	0	0
Rac1/GDP	0.019	0.005	-10000	0	-10000	0	0
TGFBR2	0.022	0.032	-10000	0	-0.46	2	2
ITGB3	0.01	0.087	-10000	0	-0.41	21	21
IGF1	-0.053	0.18	-10000	0	-0.46	85	85
RAC1	0.026	0.007	-10000	0	-10000	0	0
regulation of cell-matrix adhesion	0.033	0.066	-10000	0	-0.26	22	22
apoptosis	0.025	0.026	-10000	0	-0.39	2	2
CD47	0.025	0.009	-10000	0	-10000	0	0
alphaV/beta3 Integrin/CD47	0.034	0.065	-10000	0	-0.25	22	22
VCL	0.027	0.004	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.003	0.12	-10000	0	-0.27	82	82
CSF1	0.022	0.053	-10000	0	-0.46	6	6
PIK3C2A	0.006	0.055	-10000	0	-0.35	2	2
PI4 Kinase/Pyk2	0.006	0.084	-10000	0	-0.42	5	5
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.048	0.07	-10000	0	-0.23	24	24
FAK1/Vinculin	0.014	0.098	0.29	10	-0.39	4	14
alphaV beta3/Integrin/ppsTEM5	0.034	0.067	-10000	0	-0.26	22	22
RHOA	0.025	0.009	-10000	0	-10000	0	0
VTN	0.001	0.1	-10000	0	-0.39	32	32
BCAR1	0.027	0.006	-10000	0	-10000	0	0
FGF2	0.011	0.085	-10000	0	-0.44	17	17
F11R	0.003	0.062	-10000	0	-0.32	18	18
alphaV/beta3 Integrin/Lactadherin	0.039	0.064	-10000	0	-0.25	22	22
alphaV/beta3 Integrin/TGFBR2	0.032	0.067	-10000	0	-0.25	25	25
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.054	0.045	-10000	0	-0.26	5	5
HSP90AA1	0.026	0.007	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	0.032	0.059	-10000	0	-0.22	23	23
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	-0.15	0.2	-10000	0	-0.39	222	222
alphaV/beta3 Integrin/Pyk2	0.033	0.065	-10000	0	-0.28	7	7
SDC1	0.028	0.003	-10000	0	-10000	0	0
VAV3	0	0.077	-10000	0	-0.46	3	3
PTPN11	0.028	0.002	-10000	0	-10000	0	0
IRS1	0.024	0.038	-10000	0	-0.46	3	3
FAK1/Paxillin	0.013	0.099	0.29	11	-0.39	4	15
cell migration	0.01	0.092	0.26	15	-0.36	4	19
ITGAV	0.025	0.027	-10000	0	-0.39	2	2
PI3K	0.014	0.095	-10000	0	-0.4	7	7
SPP1	-0.2	0.21	-10000	0	-0.39	279	279
KDR	0.025	0.031	-10000	0	-0.46	2	2
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.025	0.027	-10000	0	-0.39	2	2
COL4A3	-0.025	0.14	-10000	0	-0.41	59	59
angiogenesis	-0.051	0.14	-10000	0	-0.5	32	32
Rac1/GTP	0.014	0.073	-10000	0	-0.43	3	3
EDIL3	-0.038	0.16	-10000	0	-0.42	73	73
cell proliferation	0.032	0.067	-10000	0	-0.25	25	25

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	-0.02	0.12	0.26	3	-0.44	16	19
ACTA1	-0.093	0.12	0.21	2	-0.32	74	76
NUMA1	-0.029	0.13	0.25	3	-0.33	49	52
SPTAN1	-0.031	0.11	0.3	5	-0.32	38	43
LIMK1	-0.031	0.11	0.26	6	-0.31	40	46
BIRC3	0.012	0.071	-10000	0	-0.39	15	15
BIRC2	0.024	0.01	-10000	0	-10000	0	0
BAX	0.027	0.004	-10000	0	-10000	0	0
CASP10	-0.057	0.12	-10000	0	-0.31	87	87
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.028	0.004	-10000	0	-10000	0	0
PTK2	-0.017	0.1	0.24	3	-0.37	10	13
DIABLO	0.028	0.002	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.031	0.11	0.3	5	-0.31	38	43
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.028	0.002	-10000	0	-10000	0	0
GSN	-0.031	0.11	0.26	5	-0.32	38	43
MADD	0.027	0.005	-10000	0	-10000	0	0
TFAP2A	-0.014	0.21	-10000	0	-0.84	26	26
BID	-0.019	0.061	-10000	0	-0.2	40	40
MAP3K1	-0.021	0.1	0.19	1	-0.42	26	27
TRADD	0.027	0.006	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.04	0.009	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.027	0.12	0.31	6	-0.32	37	43
CASP9	0.027	0.006	-10000	0	-10000	0	0
DNA repair	0.003	0.05	0.19	3	-0.17	4	7
neuron apoptosis	-0.001	0.14	-10000	0	-0.7	18	18
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.036	0.14	0.27	4	-0.34	49	53
APAF1	0.028	0.002	-10000	0	-10000	0	0
CASP6	-0.011	0.16	-10000	0	-0.91	13	13
TRAF2	0.023	0.041	-10000	0	-0.39	5	5
ICAD/CAD	-0.034	0.11	0.26	5	-0.31	39	44
CASP7	-0.007	0.083	0.29	4	-0.72	1	5
KRT18	0.007	0.072	-10000	0	-0.5	8	8
apoptosis	-0.031	0.12	0.26	3	-0.4	15	18
DFFA	-0.035	0.11	0.26	4	-0.32	38	42
DFFB	-0.034	0.11	0.27	5	-0.32	40	45
PARP1	-0.003	0.051	0.17	4	-0.19	3	7
actin filament polymerization	0.023	0.12	0.3	37	-0.33	15	52
TNF	0.008	0.088	-10000	0	-0.4	23	23
CYCS	-0.005	0.066	0.18	5	-0.24	7	12
SATB1	-0.021	0.15	-10000	0	-0.82	14	14
SLK	-0.035	0.11	0.24	5	-0.31	41	46
p15 BID/BAX	0.002	0.072	0.2	2	-0.26	2	4
CASP2	0.015	0.06	0.21	4	-0.37	4	8
JNK cascade	0.02	0.1	0.42	26	-0.19	1	27
CASP3	-0.036	0.12	0.27	4	-0.33	42	46
LMNB2	0.008	0.12	0.24	2	-0.48	21	23
RIPK1	0.027	0.006	-10000	0	-10000	0	0
CASP4	0.024	0.023	-10000	0	-0.46	1	1
Mammalian IAPs/DIABLO	0.054	0.05	-10000	0	-10000	0	0
negative regulation of DNA binding	-0.012	0.2	-10000	0	-0.82	26	26
stress fiber formation	-0.035	0.11	0.24	5	-0.31	40	45
GZMB	-0.05	0.15	-10000	0	-0.36	88	88
CASP1	0.013	0.032	-10000	0	-0.7	1	1
LMNB1	0.002	0.13	0.24	2	-0.49	23	25
APP	-0.002	0.14	-10000	0	-0.71	18	18
TNFRSF1A	0.026	0.007	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.007	0.002	-10000	0	-10000	0	0
VIM	-0.029	0.12	0.26	3	-0.32	43	46
LMNA	0.018	0.092	0.2	5	-0.44	13	18
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.019	0.059	-10000	0	-0.33	6	6
LRDD	0	0	-10000	0	-10000	0	0
SREBF1	-0.034	0.11	0.25	4	-0.32	39	43
APAF-1/Caspase 9	-0.006	0.11	-10000	0	-0.6	16	16
nuclear fragmentation during apoptosis	-0.028	0.13	0.25	3	-0.32	49	52
CFL2	-0.024	0.12	0.33	15	-0.3	37	52
GAS2	-0.063	0.13	0.24	5	-0.33	58	63
positive regulation of apoptosis	0.012	0.12	0.21	5	-0.48	20	25
PRF1	-0.004	0.11	-10000	0	-0.39	39	39

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.15	0.14	-10000	0	-0.54	15	15
IHH	-0.038	0.058	-10000	0	-0.37	3	3
SHH Np/Cholesterol/GAS1	0.004	0.066	-10000	0	-0.21	44	44
LRPAP1	0.026	0.007	-10000	0	-10000	0	0
dorsoventral neural tube patterning	-0.004	0.065	0.21	44	-10000	0	44
SMO/beta Arrestin2	-0.084	0.12	-10000	0	-0.45	26	26
SMO	-0.09	0.12	-10000	0	-0.47	27	27
AKT1	-0.038	0.1	-10000	0	-0.51	14	14
ARRB2	0.027	0.006	-10000	0	-10000	0	0
BOC	-0.017	0.14	-10000	0	-0.46	44	44
ADRBK1	0.026	0.008	-10000	0	-10000	0	0
heart looping	-0.088	0.12	-10000	0	-0.46	27	27
STIL	-0.085	0.096	-10000	0	-0.43	11	11
DHH N/PTCH2	0.03	0.059	-10000	0	-0.3	15	15
DHH N/PTCH1	-0.084	0.099	-10000	0	-0.49	8	8
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
DHH	0.021	0.029	-10000	0	-0.39	2	2
PTHLH	-0.21	0.18	-10000	0	-0.59	27	27
determination of left/right symmetry	-0.088	0.12	-10000	0	-0.46	27	27
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
skeletal system development	-0.21	0.18	-10000	0	-0.59	27	27
IHH N/Hhip	-0.032	0.084	-10000	0	-0.32	33	33
DHH N/Hhip	0.018	0.076	-10000	0	-0.28	32	32
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.088	0.12	-10000	0	-0.46	27	27
pancreas development	-0.006	0.097	-10000	0	-0.39	30	30
HHAT	0.028	0.004	-10000	0	-10000	0	0
PI3K	0.027	0.03	-10000	0	-0.33	2	2
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	0.021	0.051	-10000	0	-0.41	7	7
somite specification	-0.088	0.12	-10000	0	-0.46	27	27
SHH Np/Cholesterol/PTCH1	-0.089	0.096	-10000	0	-0.35	31	31
SHH Np/Cholesterol/PTCH2	0.001	0.075	-10000	0	-0.23	48	48
SHH Np/Cholesterol/Megalin	-0.007	0.081	-10000	0	-0.23	52	52
SHH	-0.018	0.073	-10000	0	-0.27	38	38
catabolic process	-0.099	0.1	-10000	0	-0.43	14	14
SMO/Vitamin D3	-0.085	0.11	-10000	0	-0.46	14	14
SHH Np/Cholesterol/Hhip	-0.01	0.084	-10000	0	-0.23	60	60
LRP2	-0.001	0.091	-10000	0	-0.39	26	26
receptor-mediated endocytosis	-0.087	0.11	-10000	0	-0.47	15	15
SHH Np/Cholesterol/BOC	-0.015	0.092	-10000	0	-0.24	73	73
SHH Np/Cholesterol/CDO	0	0.07	-10000	0	-0.22	48	48
mesenchymal cell differentiation	0.01	0.084	0.23	60	-10000	0	60
mol:Vitamin D3	-0.086	0.1	0.37	1	-0.38	19	20
IHH N/PTCH2	-0.02	0.069	-10000	0	-0.34	16	16
CDON	0.016	0.068	-10000	0	-0.46	10	10
IHH N/PTCH1	-0.097	0.11	-10000	0	-0.44	14	14
Megalin/LRPAP1	0.022	0.068	-10000	0	-0.27	26	26
PTCH2	0.016	0.073	-10000	0	-0.43	13	13
SHH Np/Cholesterol	-0.001	0.058	-10000	0	-0.2	38	38
PTCH1	-0.099	0.1	-10000	0	-0.44	14	14
HHIP	-0.006	0.098	-10000	0	-0.39	30	30

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.042	0.15	-10000	0	-0.39	85	85
Jak2/Leptin Receptor	-0.06	0.17	-10000	0	-0.48	47	47
PTP1B/AKT1	-0.021	0.099	0.19	1	-0.34	17	18
FYN	0.027	0.019	-10000	0	-0.39	1	1
p210 bcr-abl/PTP1B	-0.031	0.1	0.23	3	-0.32	30	33
EGFR	0.012	0.047	-10000	0	-0.47	4	4
EGF/EGFR	-0.051	0.13	-10000	0	-0.33	51	51
CSF1	0.022	0.053	-10000	0	-0.46	6	6
AKT1	0.026	0.007	-10000	0	-10000	0	0
INSR	0.027	0.022	-10000	0	-0.46	1	1
PTP1B/N-cadherin	-0.043	0.12	0.26	1	-0.33	32	33
Insulin Receptor/Insulin	-0.008	0.099	-10000	0	-0.38	8	8
HCK	0.024	0.029	-10000	0	-0.42	2	2
CRK	0.027	0.006	-10000	0	-10000	0	0
TYK2	-0.029	0.099	0.22	2	-0.34	19	21
EGF	-0.067	0.19	-10000	0	-0.47	98	98
YES1	0.025	0.009	-10000	0	-10000	0	0
CAV1	-0.037	0.12	0.21	12	-0.34	31	43
TXN	0.026	0.006	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.012	0.11	0.24	2	-0.37	14	16
cell migration	0.031	0.1	0.32	30	-0.23	3	33
STAT3	0.027	0.003	-10000	0	-10000	0	0
PRLR	-0.062	0.18	-10000	0	-0.46	90	90
ITGA2B	-0.014	0.12	-10000	0	-0.39	51	51
CSF1R	0.025	0.031	-10000	0	-0.46	2	2
Prolactin Receptor/Prolactin	-0.035	0.14	-10000	0	-0.34	91	91
FGR	0.027	0.019	-10000	0	-0.39	1	1
PTP1B/p130 Cas	-0.02	0.1	0.23	2	-0.33	22	24
Crk/p130 Cas	-0.009	0.1	0.24	2	-0.36	13	15
DOK1	-0.039	0.11	0.24	3	-0.36	23	26
JAK2	-0.071	0.18	-10000	0	-0.47	56	56
Jak2/Leptin Receptor/Leptin	-0.047	0.14	0.23	1	-0.44	20	21
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
PTPN1	-0.031	0.1	0.23	3	-0.32	30	33
LYN	0.024	0.02	-10000	0	-0.39	1	1
CDH2	-0.03	0.14	-10000	0	-0.4	66	66
SRC	0.002	0.11	-10000	0	-0.56	15	15
ITGB3	0.009	0.088	-10000	0	-0.41	21	21
CAT1/PTP1B	-0.086	0.15	0.22	8	-0.42	36	44
CAPN1	0.026	0.007	-10000	0	-10000	0	0
CSK	0.027	0.004	-10000	0	-10000	0	0
PI3K	0.011	0.083	-10000	0	-0.37	4	4
mol:H2O2	0	0.004	-10000	0	-10000	0	0
STAT3 (dimer)	-0.038	0.13	0.21	1	-0.39	20	21
negative regulation of transcription	-0.07	0.17	-10000	0	-0.46	56	56
FCGR2A	0.007	0.091	-10000	0	-0.39	26	26
FER	0.023	0.032	-10000	0	-0.47	2	2
alphaIIb/beta3 Integrin	-0.004	0.11	-10000	0	-0.29	69	69
BLK	-0.035	0.14	-10000	0	-0.4	70	70
Insulin Receptor/Insulin/Shc	0.045	0.027	-10000	0	-0.25	3	3
RHOA	0.024	0.009	-10000	0	-10000	0	0
LEPR	0.026	0.031	-10000	0	-0.46	2	2
BCAR1	0.027	0.006	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.027	0.004	-10000	0	-10000	0	0
mol:NADPH	-0.001	0.003	-10000	0	-10000	0	0
TRPV6	-0.075	0.14	0.24	3	-0.44	30	33
PRL	-0.002	0.044	-10000	0	-0.39	5	5
SOCS3	0.025	0.1	-10000	0	-1.1	4	4
SPRY2	0.02	0.058	-10000	0	-0.47	7	7
Insulin Receptor/Insulin/IRS1	0.042	0.037	-10000	0	-0.27	6	6
CSF1/CSF1R	-0.013	0.11	0.27	1	-0.35	17	18
Ras protein signal transduction	0.013	0.075	0.56	8	-10000	0	8
IRS1	0.024	0.038	-10000	0	-0.46	3	3
INS	-0.001	0.031	-10000	0	-0.39	2	2
LEP	-0.049	0.16	-10000	0	-0.43	75	75
STAT5B	-0.039	0.12	0.21	3	-0.38	34	37
STAT5A	-0.039	0.12	0.23	2	-0.38	34	36
GRB2	0.027	0.004	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.049	0.13	0.23	2	-0.34	32	34
CSN2	-0.013	0.094	-10000	0	-0.52	4	4
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
LAT	0.002	0.08	-10000	0	-0.56	6	6
YBX1	0.033	0.006	-10000	0	-10000	0	0
LCK	0.018	0.063	-10000	0	-0.39	12	12
SHC1	0.028	0.004	-10000	0	-10000	0	0
NOX4	-0.045	0.16	-10000	0	-0.39	87	87

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.021	0.002	-10000	0	-10000	0	0
PRKCZ	0.026	0.022	-10000	0	-0.46	1	1
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.026	0.008	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.004	0.067	-10000	0	-0.43	3	3
IRAK/TOLLIP	0.03	0.01	-10000	0	-10000	0	0
IKBKB	0.026	0.008	-10000	0	-10000	0	0
IKBKG	0.027	0.006	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.11	0.18	-10000	0	-0.31	213	213
IL1A	-0.079	0.18	-10000	0	-0.39	131	131
IL1B	-0.015	0.087	-10000	0	-0.28	51	51
IRAK/TRAF6/p62/Atypical PKCs	0.046	0.035	-10000	0	-10000	0	0
IL1R2	-0.064	0.19	-10000	0	-0.46	97	97
IL1R1	0.027	0.022	-10000	0	-0.46	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.015	0.057	0.25	1	-0.62	1	2
TOLLIP	0.027	0.006	-10000	0	-10000	0	0
TICAM2	0.026	0.008	-10000	0	-10000	0	0
MAP3K3	0.028	0.003	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.018	0.003	-10000	0	-10000	0	0
IKK complex/ELKS	0.041	0.053	-10000	0	-10000	0	0
JUN	-0.013	0.053	0.16	13	-0.4	1	14
MAP3K7	0.027	0.005	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.027	0.08	-10000	0	-0.66	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.011	0.11	-10000	0	-0.41	3	3
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.004	0.11	-10000	0	-0.39	3	3
IL1 beta fragment/IL1R1/IL1RAP	0.01	0.075	-10000	0	-0.22	41	41
NFKB1	0.027	0.005	-10000	0	-10000	0	0
MAPK8	-0.013	0.056	0.17	13	-0.22	25	38
IRAK1	0.015	0.003	-10000	0	-10000	0	0
IL1RN/IL1R1	-0.051	0.16	-10000	0	-0.33	126	126
IRAK4	0.027	0.022	-10000	0	-0.46	1	1
PRKCI	0.02	0.013	-10000	0	-10000	0	0
TRAF6	0.027	0.006	-10000	0	-10000	0	0
PI3K	0.027	0.03	-10000	0	-0.33	2	2
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.017	0.064	-10000	0	-0.44	3	3
CHUK	0.027	0.005	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.01	0.075	-10000	0	-0.22	41	41
IL1 beta/IL1R2	-0.048	0.14	0.22	2	-0.27	134	136
IRAK/TRAF6/TAK1/TAB1/TAB2	0.037	0.013	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.015	0.07	-10000	0	-0.61	1	1
IRAK3	0.022	0.044	-10000	0	-0.42	5	5
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.028	0.081	-10000	0	-0.66	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.01	0.069	-10000	0	-0.55	2	2
IL1 alpha/IL1R1/IL1RAP	-0.02	0.12	-10000	0	-0.24	106	106
RELA	0.027	0.006	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.026	0.007	-10000	0	-10000	0	0
MYD88	0.024	0.009	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0.045	0.016	-10000	0	-10000	0	0
IL1RAP	0.018	0.031	-10000	0	-0.42	2	2
UBE2N	0.028	0.002	-10000	0	-10000	0	0
IRAK/TRAF6	0.008	0.061	-10000	0	-0.57	1	1
CASP1	0.024	0.023	-10000	0	-0.46	1	1
IL1RN/IL1R2	-0.11	0.22	-10000	0	-0.39	182	182
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.017	0.077	-10000	0	-0.68	1	1
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.004	0.088	-10000	0	-0.75	1	1
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
IL1RN	-0.093	0.21	-10000	0	-0.46	126	126
TRAF6/TAK1/TAB1/TAB2	0.038	0.011	-10000	0	-10000	0	0
MAP2K6	0.008	0.06	0.19	15	-0.22	24	39

×

BCR signaling 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
JUN	-0.02	0.12	0.25	5	-0.38	19	24
IKBKB	0.006	0.1	0.26	13	-0.33	13	26
AKT1	0.005	0.11	0.28	31	-0.24	11	42
IKBKG	0.016	0.083	0.25	11	-0.29	5	16
CALM1	-0.006	0.098	0.28	9	-0.39	9	18
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
MAP3K1	-0.029	0.15	0.31	5	-0.52	22	27
MAP3K7	0.027	0.005	-10000	0	-10000	0	0
mol:Ca2+	-0.01	0.099	0.27	3	-0.4	11	14
DOK1	0.027	0.018	-10000	0	-0.39	1	1
AP-1	-0.013	0.091	0.23	13	-0.25	10	23
LYN	0.024	0.02	-10000	0	-0.39	1	1
BLNK	-0.017	0.14	-10000	0	-0.46	47	47
SHC1	0.028	0.004	-10000	0	-10000	0	0
BCR complex	-0.038	0.16	-10000	0	-0.34	106	106
CD22	-0.05	0.15	-10000	0	-0.43	50	50
CAMK2G	-0.004	0.094	0.27	9	-0.39	7	16
CSNK2A1	0.026	0.007	-10000	0	-10000	0	0
INPP5D	0.025	0.031	-10000	0	-0.46	2	2
SHC/GRB2/SOS1	-0.039	0.12	-10000	0	-0.38	28	28
GO:0007205	-0.011	0.1	0.27	3	-0.4	11	14
SYK	0.024	0.038	-10000	0	-0.46	3	3
ELK1	-0.01	0.097	0.26	4	-0.38	11	15
NFATC1	-0.045	0.13	0.26	6	-0.38	33	39
B-cell antigen/BCR complex	-0.038	0.16	-10000	0	-0.34	106	106
PAG1/CSK	0.036	0.02	-10000	0	-0.27	1	1
NFKBIB	0.018	0.046	0.13	18	-0.13	16	34
HRAS	-0.014	0.1	0.26	5	-0.4	10	15
NFKBIA	0.018	0.046	0.13	17	-0.12	15	32
NF-kappa-B/RelA/I kappa B beta	0.022	0.041	0.13	17	-10000	0	17
RasGAP/Csk	0.004	0.14	-10000	0	-0.33	47	47
mol:GDP	-0.008	0.097	0.26	3	-0.38	12	15
PTEN	0.027	0.006	-10000	0	-10000	0	0
CD79B	0.004	0.099	-10000	0	-0.41	27	27
NF-kappa-B/RelA/I kappa B alpha	0.022	0.04	0.13	17	-10000	0	17
GRB2	0.027	0.004	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.047	0.16	0.29	2	-0.52	21	23
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
mol:IP3	-0.012	0.099	0.27	2	-0.41	11	13
CSK	0.027	0.004	-10000	0	-10000	0	0
FOS	-0.031	0.12	0.27	11	-0.38	21	32
CHUK	0.008	0.094	0.25	10	-0.33	12	22
IBTK	0.027	0.004	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	0.005	0.11	0.24	2	-0.38	11	13
PTPN6	-0.049	0.14	-10000	0	-0.49	29	29
RELA	0.027	0.006	-10000	0	-10000	0	0
BCL2A1	0.015	0.033	0.11	7	-0.11	1	8
VAV2	-0.059	0.16	-10000	0	-0.49	33	33
ubiquitin-dependent protein catabolic process	0.021	0.046	0.13	17	-0.13	16	33
BTK	0.018	0.05	-10000	0	-1	1	1
CD19	-0.062	0.16	-10000	0	-0.39	74	74
MAP4K1	0.015	0.07	-10000	0	-0.4	14	14
CD72	-0.014	0.12	-10000	0	-0.39	47	47
PAG1	0.024	0.02	-10000	0	-0.39	1	1
MAPK14	-0.021	0.13	0.28	7	-0.45	20	27
SH3BP5	0.022	0.038	-10000	0	-0.46	3	3
PIK3AP1	-0.017	0.11	-10000	0	-0.39	17	17
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.036	0.13	-10000	0	-0.47	22	22
RAF1	-0.013	0.096	0.27	4	-0.38	9	13
RasGAP/p62DOK/SHIP	0.003	0.14	-10000	0	-0.41	26	26
CD79A	-0.06	0.17	-10000	0	-0.41	103	103
re-entry into mitotic cell cycle	-0.013	0.091	0.24	12	-0.25	10	22
RASA1	0.024	0.031	-10000	0	-0.46	2	2
MAPK3	-0.009	0.087	0.26	5	-0.33	8	13
MAPK1	-0.006	0.09	0.25	9	-0.32	8	17
CD72/SHP1	-0.041	0.16	0.32	6	-0.52	32	38
NFKB1	0.027	0.005	-10000	0	-10000	0	0
MAPK8	-0.025	0.13	0.3	5	-0.43	22	27
actin cytoskeleton organization	-0.044	0.14	0.3	3	-0.43	32	35
NF-kappa-B/RelA	0.047	0.078	0.25	17	-10000	0	17
Calcineurin	0.016	0.096	0.27	6	-0.36	7	13
PI3K	-0.052	0.13	-10000	0	-0.4	44	44
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.011	0.1	-10000	0	-0.42	14	14
SOS1	0.028	0.004	-10000	0	-10000	0	0
Bam32/HPK1	-0.032	0.2	-10000	0	-0.7	33	33
DAPP1	-0.046	0.21	-10000	0	-0.77	33	33
cytokine secretion	-0.042	0.12	0.26	6	-0.36	33	39
mol:DAG	-0.012	0.099	0.27	2	-0.41	11	13
PLCG2	0.025	0.023	-10000	0	-0.46	1	1
MAP2K1	-0.01	0.093	0.26	5	-0.36	9	14
B-cell antigen/BCR complex/FcgammaRIIB	-0.02	0.15	-10000	0	-0.3	107	107
mol:PI-3-4-5-P3	-0.033	0.1	-10000	0	-0.29	39	39
ETS1	-0.006	0.088	0.26	10	-0.36	7	17
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.021	0.15	-10000	0	-0.31	77	77
B-cell antigen/BCR complex/LYN	-0.032	0.14	-10000	0	-0.54	20	20
MALT1	0.025	0.009	-10000	0	-10000	0	0
TRAF6	0.027	0.006	-10000	0	-10000	0	0
RAC1	-0.049	0.15	0.28	2	-0.46	32	34
B-cell antigen/BCR complex/LYN/SYK	-0.021	0.16	0.36	1	-0.44	45	46
CARD11	-0.011	0.12	0.28	11	-0.39	18	29
FCGR2B	0.021	0.057	-10000	0	-0.46	7	7
PPP3CA	0.027	0.005	-10000	0	-10000	0	0
BCL10	0.027	0.004	-10000	0	-10000	0	0
IKK complex	0.016	0.054	0.16	30	-0.12	8	38
PTPRC	0.017	0.069	-10000	0	-0.42	12	12
PDPK1	-0.005	0.1	0.24	31	-0.22	17	48
PPP3CB	0.028	0.004	-10000	0	-10000	0	0
PPP3CC	0.026	0.008	-10000	0	-10000	0	0
POU2F2	0.016	0.035	0.13	7	-10000	0	7

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.01	0.011	-10000	0	-10000	0	0
SMARCC1	0.004	0.035	-10000	0	-0.6	1	1
REL	0.022	0.065	-10000	0	-0.46	9	9
HDAC7	-0.091	0.14	0.23	2	-0.48	25	27
JUN	0.026	0.005	-10000	0	-10000	0	0
EP300	0.026	0.022	-10000	0	-0.46	1	1
KAT2B	0.006	0.092	-10000	0	-0.46	19	19
KAT5	0.027	0.007	-10000	0	-10000	0	0
MAPK14	-0.023	0.079	-10000	0	-0.35	25	25
FOXO1	0.026	0.007	-10000	0	-10000	0	0
T-DHT/AR	-0.085	0.16	-10000	0	-0.47	29	29
MAP2K6	-0.017	0.11	-10000	0	-0.48	25	25
BRM/BAF57	0.023	0.034	-10000	0	-0.33	1	1
MAP2K4	0.006	0.026	-10000	0	-10000	0	0
SMARCA2	0.015	0.029	-10000	0	-0.46	1	1
PDE9A	-0.079	0.22	-10000	0	-0.99	21	21
NCOA2	-0.009	0.12	-10000	0	-0.46	36	36
CEBPA	0.025	0.038	-10000	0	-0.46	3	3
EHMT2	0.025	0.007	-10000	0	-10000	0	0
cell proliferation	-0.077	0.16	0.29	11	-0.44	29	40
NR0B1	-0.02	0.084	-10000	0	-0.39	24	24
EGR1	-0.001	0.099	-10000	0	-0.46	22	22
RXRs/9cRA	0.004	0.099	-10000	0	-0.26	60	60
AR/RACK1/Src	-0.042	0.11	0.25	3	-0.39	22	25
AR/GR	-0.062	0.14	-10000	0	-0.32	74	74
GNB2L1	0.027	0.007	-10000	0	-10000	0	0
PKN1	0.026	0.026	-10000	0	-0.39	2	2
RCHY1	0.027	0.005	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0.001	-10000	0	-10000	0	0
MAPK8	-0.009	0.04	-10000	0	-0.35	4	4
T-DHT/AR/TIF2/CARM1	-0.05	0.13	-10000	0	-0.38	31	31
SRC	-0.036	0.078	0.2	13	-0.31	23	36
NR3C1	0.027	0.006	-10000	0	-10000	0	0
KLK3	-0.24	0.43	0.37	1	-1.2	87	88
APPBP2	0.006	0.026	-10000	0	-10000	0	0
TRIM24	0.018	0.029	-10000	0	-0.46	1	1
T-DHT/AR/TIP60	-0.046	0.11	0.23	1	-0.4	20	21
TMPRSS2	-0.46	0.53	-10000	0	-1	240	240
RXRG	-0.037	0.16	-10000	0	-0.46	63	63
mol:9cRA	-0.001	0.003	-10000	0	-10000	0	0
RXRA	0.027	0.005	-10000	0	-10000	0	0
RXRB	0.026	0.006	-10000	0	-10000	0	0
CARM1	0.028	0.004	-10000	0	-10000	0	0
NR2C2	0.018	0.053	-10000	0	-0.46	6	6
KLK2	-0.043	0.12	-10000	0	-0.44	10	10
AR	-0.076	0.14	-10000	0	-0.31	111	111
SENP1	0.027	0.003	-10000	0	-10000	0	0
HSP90AA1	0.026	0.007	-10000	0	-10000	0	0
MDM2	0.031	0.013	-10000	0	-10000	0	0
SRY	0.005	0.011	0.029	90	-10000	0	90
GATA2	0.023	0.03	-10000	0	-0.42	2	2
MYST2	0.001	0.001	-10000	0	-10000	0	0
HOXB13	-0.14	0.19	-10000	0	-0.39	193	193
T-DHT/AR/RACK1/Src	-0.039	0.11	0.26	3	-0.4	22	25
positive regulation of transcription	0.023	0.03	-10000	0	-0.42	2	2
DNAJA1	0.005	0.025	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.021	0.008	-10000	0	-10000	0	0
NCOA1	0.034	0.028	-10000	0	-10000	0	0
SPDEF	-0.1	0.2	-10000	0	-0.45	128	128
T-DHT/AR/TIF2	-0.05	0.13	0.21	1	-0.41	31	32
T-DHT/AR/Hsp90	-0.049	0.11	-10000	0	-0.4	23	23
GSK3B	0.022	0.009	-10000	0	-10000	0	0
NR2C1	0.029	0.004	-10000	0	-10000	0	0
mol:T-DHT	-0.043	0.074	-10000	0	-0.32	26	26
SIRT1	0.026	0.022	-10000	0	-0.46	1	1
ZMIZ2	0.031	0.014	-10000	0	-10000	0	0
POU2F1	-0.024	0.07	-10000	0	-10000	0	0
T-DHT/AR/DAX-1	-0.063	0.12	-10000	0	-0.4	27	27
CREBBP	0.027	0.004	-10000	0	-10000	0	0
SMARCE1	0.019	0.02	-10000	0	-10000	0	0

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.026	0.007	-10000	0	-10000	0	0
VLDLR	0.02	0.049	-10000	0	-0.46	5	5
LRPAP1	0.026	0.007	-10000	0	-10000	0	0
NUDC	0.027	0.005	-10000	0	-10000	0	0
RELN/LRP8	-0.022	0.14	-10000	0	-0.28	109	109
CaM/Ca2+	0.019	0.005	-10000	0	-10000	0	0
KATNA1	0.027	0.004	-10000	0	-10000	0	0
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	-0.032	0.12	0.18	29	-0.26	96	125
IQGAP1/CaM	0.038	0.011	-10000	0	-10000	0	0
DAB1	-0.001	0.073	-10000	0	-0.39	16	16
IQGAP1	0.027	0.004	-10000	0	-10000	0	0
PLA2G7	-0.13	0.2	-10000	0	-0.39	198	198
CALM1	0.026	0.007	-10000	0	-10000	0	0
DYNLT1	0.027	0.005	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	0.033	0.044	-10000	0	-0.27	10	10
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0.027	0.022	-10000	0	-0.46	1	1
CDK5R1	0.026	0.026	-10000	0	-0.39	2	2
LIS1/Poliovirus Protein 3A	0.01	0.003	-10000	0	-10000	0	0
CDK5R2	-0.044	0.14	-10000	0	-0.39	74	74
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.03	0.14	-10000	0	-0.28	113	113
YWHAE	0.027	0.006	-10000	0	-10000	0	0
NDEL1/14-3-3 E	-0.03	0.12	0.3	5	-0.33	10	15
MAP1B	0.003	0.027	-10000	0	-0.33	2	2
RAC1	0.014	0.006	-10000	0	-10000	0	0
p35/CDK5	-0.023	0.11	-10000	0	-0.4	4	4
RELN	-0.073	0.2	-10000	0	-0.46	103	103
PAFAH/LIS1	-0.067	0.12	-10000	0	-0.23	183	183
LIS1/CLIP170	0.029	0.01	-10000	0	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.022	0.097	-10000	0	-0.38	1	1
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.036	0.12	-10000	0	-0.38	24	24
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	-0.041	0.12	0.29	4	-0.34	12	16
LIS1/IQGAP1	0.028	0.01	-10000	0	-10000	0	0
RHOA	0.013	0.006	-10000	0	-10000	0	0
PAFAH1B1	0.014	0.005	-10000	0	-10000	0	0
PAFAH1B3	0.026	0.026	-10000	0	-0.39	2	2
PAFAH1B2	0.023	0.032	-10000	0	-0.46	2	2
MAP1B/LIS1/Dynein heavy chain	0.019	0.035	-10000	0	-0.26	1	1
NDEL1/Katanin 60/Dynein heavy chain	-0.021	0.12	0.3	4	-0.38	3	7
LRP8	0.02	0.057	-10000	0	-0.39	10	10
NDEL1/Katanin 60	-0.031	0.12	0.3	5	-0.33	10	15
P39/CDK5	-0.052	0.13	-10000	0	-0.4	14	14
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.028	0.011	-10000	0	-10000	0	0
CDK5	-0.046	0.11	0.18	25	-0.42	3	28
PPP2R5D	0.027	0.006	-10000	0	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.025	0.01	-10000	0	-10000	0	0
CSNK2A1	0.026	0.007	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.018	0.12	-10000	0	-0.39	3	3
RELN/VLDLR	-0.012	0.13	-10000	0	-0.26	96	96
CDC42	0.014	0.006	-10000	0	-10000	0	0

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	0.015	0.07	-10000	0	-0.27	29	29
EFNA5	0.005	0.099	-10000	0	-0.46	22	22
FYN	-0.008	0.063	0.18	5	-0.25	28	33
neuron projection morphogenesis	0.015	0.07	-10000	0	-0.27	29	29
cell-cell signaling	0	0	-10000	0	-10000	0	0
Ephrin A5/EPHA5	0.015	0.071	-10000	0	-0.27	29	29
EPHA5	0.002	0.051	-10000	0	-0.39	7	7

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.047	0.13	-10000	0	-0.25	148	148
cell-cell adhesion	0.044	0.088	0.43	5	-10000	0	5
Ephrin B/EPHB2/RasGAP	-0.017	0.14	-10000	0	-0.28	26	26
ITSN1	0.027	0.005	-10000	0	-10000	0	0
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
SHC1	0.028	0.004	-10000	0	-10000	0	0
Ephrin B1/EPHB3	0.021	0.044	-10000	0	-0.28	9	9
Ephrin B1/EPHB1	0.02	0.058	-10000	0	-0.25	21	21
HRAS/GDP	-0.011	0.1	-10000	0	-0.35	8	8
Ephrin B/EPHB1/GRB7	0.039	0.09	-10000	0	-0.47	2	2
Endophilin/SYNJ1	-0.048	0.1	0.21	1	-0.39	4	5
KRAS	0.026	0.007	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	0.04	0.085	-10000	0	-0.47	2	2
endothelial cell migration	0.037	0.034	-10000	0	-0.24	2	2
GRB2	0.027	0.004	-10000	0	-10000	0	0
GRB7	0.025	0.038	-10000	0	-0.46	3	3
PAK1	-0.043	0.12	0.32	4	-0.46	9	13
HRAS	0.026	0.02	-10000	0	-0.4	1	1
RRAS	-0.048	0.11	0.21	1	-0.39	5	6
DNM1	0	0.1	-10000	0	-0.39	34	34
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	0.019	0.092	0.35	3	-0.44	2	5
lamellipodium assembly	-0.044	0.088	-10000	0	-0.43	5	5
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.01	0.066	-10000	0	-0.36	4	4
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
EPHB2	-0.084	0.18	-10000	0	-0.39	137	137
EPHB3	0.011	0.068	-10000	0	-0.46	10	10
EPHB1	0.004	0.09	-10000	0	-0.42	22	22
EPHB4	0.026	0.008	-10000	0	-10000	0	0
mol:GDP	-0.037	0.092	0.29	1	-0.34	13	14
Ephrin B/EPHB2	-0.024	0.13	-10000	0	-0.26	29	29
Ephrin B/EPHB3	0.028	0.07	-10000	0	-0.24	25	25
JNK cascade	0.002	0.16	0.36	51	-0.4	3	54
Ephrin B/EPHB1	0.03	0.081	-10000	0	-0.26	24	24
RAP1/GDP	-0.018	0.1	0.3	2	-0.36	4	6
EFNB2	0.026	0.022	-10000	0	-0.46	1	1
EFNB3	-0.001	0.11	-10000	0	-0.46	29	29
EFNB1	0.028	0.004	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.026	0.11	-10000	0	-0.21	129	129
RAP1B	0.027	0.006	-10000	0	-10000	0	0
RAP1A	0.027	0.005	-10000	0	-10000	0	0
CDC42/GTP	-0.02	0.11	-10000	0	-0.47	5	5
Rap1/GTP	-0.036	0.097	-10000	0	-0.44	5	5
axon guidance	-0.047	0.13	-10000	0	-0.25	148	148
MAPK3	0.004	0.061	0.19	4	-0.34	3	7
MAPK1	0.007	0.066	0.2	12	-0.33	4	16
Rac1/GDP	-0.029	0.097	0.27	2	-0.34	7	9
actin cytoskeleton reorganization	-0.049	0.081	-10000	0	-0.36	5	5
CDC42/GDP	-0.025	0.1	0.26	5	-0.33	9	14
PI3K	0.041	0.037	-10000	0	-0.24	2	2
EFNA5	0.005	0.099	-10000	0	-0.46	22	22
Ephrin B2/EPHB4	0.033	0.018	-10000	0	-0.28	1	1
Ephrin B/EPHB2/Intersectin/N-WASP	-0.024	0.086	-10000	0	-0.31	14	14
CDC42	0.027	0.005	-10000	0	-10000	0	0
RAS family/GTP	-0.037	0.094	-10000	0	-0.43	5	5
PTK2	0.092	0.21	0.6	75	-10000	0	75
MAP4K4	0.002	0.16	0.36	51	-0.4	3	54
SRC	0.026	0.007	-10000	0	-10000	0	0
KALRN	-0.009	0.12	-10000	0	-0.46	35	35
Intersectin/N-WASP	0.038	0.012	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.007	0.13	0.31	36	-0.39	8	44
MAP2K1	0.005	0.062	-10000	0	-0.34	4	4
WASL	0.027	0.006	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.016	0.12	-10000	0	-0.3	11	11
cell migration	0.01	0.093	0.29	3	-0.38	5	8
NRAS	0.027	0.005	-10000	0	-10000	0	0
SYNJ1	-0.049	0.1	0.21	1	-0.4	4	5
PXN	0.028	0.002	-10000	0	-10000	0	0
TF	-0.17	0.15	0.2	2	-0.4	103	105
HRAS/GTP	-0.024	0.11	-10000	0	-0.46	5	5
Ephrin B1/EPHB1-2	-0.026	0.11	-10000	0	-0.21	131	131
cell adhesion mediated by integrin	0	0.066	0.24	15	-0.26	8	23
RAC1	0.026	0.007	-10000	0	-10000	0	0
mol:GTP	-0.023	0.12	-10000	0	-0.48	5	5
RAC1-CDC42/GTP	-0.042	0.092	-10000	0	-0.43	6	6
RASA1	0.024	0.031	-10000	0	-0.46	2	2
RAC1-CDC42/GDP	-0.02	0.099	0.29	2	-0.36	4	6
ruffle organization	-0.021	0.13	0.36	15	-0.44	5	20
NCK1	0.023	0.011	-10000	0	-10000	0	0
receptor internalization	-0.069	0.1	0.2	3	-0.36	21	24
Ephrin B/EPHB2/KALRN	-0.029	0.14	-10000	0	-0.29	44	44
ROCK1	0.055	0.078	0.18	127	-0.25	4	131
RAS family/GDP	-0.053	0.081	-10000	0	-0.35	6	6
Rac1/GTP	-0.041	0.095	-10000	0	-0.46	5	5
Ephrin B/EPHB1/Src/Paxillin	0.008	0.068	-10000	0	-0.33	6	6

×

Plasma membrane estrogen receptor 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
GNB1/GNG2	0.04	0.072	-10000	0	-0.25	12	12
ER alpha/Gai/GDP/Gbeta gamma	-0.024	0.16	-10000	0	-0.54	32	32
AKT1	-0.005	0.16	-10000	0	-0.73	23	23
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	0	0.17	-10000	0	-0.75	23	23
mol:Ca2+	-0.032	0.13	-10000	0	-0.36	62	62
IGF1R	0.027	0.005	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	0.011	0.084	-10000	0	-0.26	43	43
SHC1	0.028	0.004	-10000	0	-10000	0	0
apoptosis	0.004	0.16	0.7	23	-10000	0	23
RhoA/GTP	0.014	0.044	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	0.014	0.14	-10000	0	-0.46	24	24
regulation of stress fiber formation	0.005	0.057	0.31	1	-0.18	1	2
E2/ERA-ERB (dimer)	0.015	0.074	-10000	0	-0.25	35	35
KRAS	0.026	0.007	-10000	0	-10000	0	0
G13/GTP	0.022	0.056	-10000	0	-0.22	24	24
pseudopodium formation	-0.005	0.057	0.18	1	-0.31	1	2
E2/ER alpha (dimer)/PELP1	0.023	0.059	-10000	0	-0.24	23	23
GRB2	0.027	0.004	-10000	0	-10000	0	0
GNG2	0.026	0.007	-10000	0	-10000	0	0
GNAO1	0.023	0.039	-10000	0	-0.41	4	4
HRAS	0.026	0.02	-10000	0	-0.4	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.007	0.16	0.27	6	-0.55	27	33
E2/ER beta (dimer)	0.012	0.047	-10000	0	-0.28	13	13
mol:GDP	0.003	0.071	-10000	0	-0.35	13	13
mol:NADP	-0.007	0.16	0.27	6	-0.55	27	33
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
mol:IP3	-0.039	0.13	-10000	0	-0.37	62	62
IGF-1R heterotetramer	0.027	0.005	-10000	0	-10000	0	0
PLCB1	-0.035	0.14	-10000	0	-0.38	63	63
PLCB2	-0.037	0.14	-10000	0	-0.37	68	68
IGF1	-0.053	0.18	-10000	0	-0.46	85	85
mol:L-citrulline	-0.007	0.16	0.27	6	-0.55	27	33
RHOA	0.025	0.009	-10000	0	-10000	0	0
Gai/GDP	-0.05	0.23	-10000	0	-0.61	68	68
JNK cascade	0.012	0.046	-10000	0	-0.27	13	13
BCAR1	0.027	0.006	-10000	0	-10000	0	0
ESR2	0.016	0.066	-10000	0	-0.39	13	13
GNAQ	0.027	0.005	-10000	0	-10000	0	0
ESR1	0.006	0.095	-10000	0	-0.42	24	24
Gq family/GDP/Gbeta gamma	-0.025	0.16	-10000	0	-0.7	21	21
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.03	0.087	-10000	0	-0.86	3	3
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	0.013	0.14	-10000	0	-0.45	26	26
GNAZ	0.012	0.079	-10000	0	-0.41	17	17
E2/ER alpha (dimer)	0.005	0.067	-10000	0	-0.3	24	24
STRN	0.008	0.097	-10000	0	-0.46	21	21
GNAL	-0.03	0.16	-10000	0	-0.46	59	59
PELP1	0.027	0.006	-10000	0	-10000	0	0
MAPK11	0.008	0.039	-10000	0	-0.23	13	13
GNAI2	0.024	0.009	-10000	0	-10000	0	0
GNAI3	0.027	0.005	-10000	0	-10000	0	0
GNAI1	0.026	0.022	-10000	0	-0.46	1	1
HBEGF	-0.083	0.17	0.32	14	-0.52	39	53
cAMP biosynthetic process	-0.015	0.097	-10000	0	-0.23	84	84
SRC	-0.017	0.16	-10000	0	-0.55	26	26
PI3K	0.027	0.03	-10000	0	-0.33	2	2
GNB1	0.027	0.006	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	0.032	0.074	-10000	0	-0.33	10	10
SOS1	0.028	0.004	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.039	0.12	-10000	0	-0.42	26	26
Gs family/GTP	-0.009	0.1	-10000	0	-0.23	84	84
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.046	0.022	-10000	0	-0.21	1	1
vasodilation	-0.005	0.15	0.26	7	-0.52	27	34
mol:DAG	-0.039	0.13	-10000	0	-0.37	62	62
Gs family/GDP/Gbeta gamma	-0.012	0.092	-10000	0	-0.37	11	11
MSN	-0.005	0.06	0.19	1	-0.33	1	2
Gq family/GTP	-0.035	0.15	-10000	0	-0.39	69	69
mol:PI-3-4-5-P3	0.001	0.16	-10000	0	-0.72	23	23
NRAS	0.027	0.005	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.005	0.15	0.52	27	-0.26	7	34
GRB2/SOS1	0.04	0.008	-10000	0	-10000	0	0
RhoA/GDP	0.016	0.071	-10000	0	-0.35	10	10
NOS3	-0.009	0.16	0.27	6	-0.58	27	33
GNA11	0.024	0.038	-10000	0	-0.46	3	3
MAPKKK cascade	0.003	0.15	-10000	0	-0.54	26	26
E2/ER alpha (dimer)/PELP1/Src	0.013	0.14	0.28	4	-0.46	28	32
ruffle organization	-0.005	0.057	0.18	1	-0.31	1	2
ROCK2	-0.004	0.065	0.2	1	-0.36	1	2
GNA14	-0.041	0.17	-10000	0	-0.46	71	71
GNA15	0.025	0.031	-10000	0	-0.46	2	2
GNA13	0.028	0.003	-10000	0	-10000	0	0
MMP9	-0.12	0.17	0.36	16	-0.53	40	56
MMP2	-0.026	0.16	0.27	9	-0.52	25	34

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.018	0.2	-10000	0	-0.84	21	21
NCK1/PAK1/Dok-R	-0.024	0.079	-10000	0	-0.39	19	19
NCK1/Dok-R	0.01	0.22	-10000	0	-1	20	20
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
mol:beta2-estradiol	-0.001	0.04	0.24	13	-10000	0	13
RELA	0.027	0.006	-10000	0	-10000	0	0
SHC1	0.028	0.004	-10000	0	-10000	0	0
Rac/GDP	0.019	0.005	-10000	0	-10000	0	0
F2	-0.041	0.13	0.27	13	-0.4	52	65
TNIP2	0.026	0.007	-10000	0	-10000	0	0
NF kappa B/RelA	0.03	0.21	-10000	0	-0.93	21	21
FN1	-0.15	0.2	-10000	0	-0.39	222	222
PLD2	-0.005	0.22	-10000	0	-1	21	21
PTPN11	0.028	0.002	-10000	0	-10000	0	0
GRB14	-0.017	0.14	-10000	0	-0.45	46	46
ELK1	0.003	0.21	-10000	0	-0.94	21	21
GRB7	0.025	0.038	-10000	0	-0.46	3	3
PAK1	0.025	0.008	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.11	0.25	-10000	0	-1	21	21
CDKN1A	0.031	0.16	0.44	1	-0.61	15	16
ITGA5	-0.1	0.19	-10000	0	-0.39	161	161
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	0.015	0.23	-10000	0	-1	21	21
CRK	0.027	0.006	-10000	0	-10000	0	0
mol:NO	0.025	0.16	0.39	3	-0.62	21	24
PLG	-0.01	0.22	-10000	0	-1	21	21
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.019	0.19	-10000	0	-0.8	21	21
GRB2	0.027	0.004	-10000	0	-10000	0	0
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
ANGPT2	0.014	0.16	-10000	0	-0.59	6	6
BMX	-0.029	0.24	-10000	0	-1.1	21	21
ANGPT1	-0.005	0.2	-10000	0	-1.2	13	13
tube development	0.021	0.17	0.37	2	-0.64	19	21
ANGPT4	0.018	0.016	-10000	0	-10000	0	0
response to hypoxia	-0.002	0.014	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.013	0.24	-10000	0	-1.1	21	21
alpha5/beta1 Integrin	-0.058	0.14	-10000	0	-0.27	161	161
FGF2	0.011	0.085	-10000	0	-0.44	17	17
STAT5A (dimer)	0.031	0.19	-10000	0	-0.75	17	17
mol:L-citrulline	0.025	0.16	0.39	3	-0.62	21	24
AGTR1	-0.02	0.13	-10000	0	-0.46	41	41
MAPK14	-0.001	0.24	-10000	0	-1	23	23
Tie2/SHP2	-0.004	0.2	-10000	0	-1.1	13	13
TEK	0	0.2	-10000	0	-1.2	13	13
RPS6KB1	0.018	0.19	-10000	0	-0.81	21	21
Angiotensin II/AT1	-0.012	0.093	-10000	0	-0.33	41	41
Tie2/Ang1/GRB2	0.007	0.24	-10000	0	-1.1	21	21
MAPK3	-0.004	0.21	-10000	0	-0.96	21	21
MAPK1	-0.002	0.21	-10000	0	-0.96	21	21
Tie2/Ang1/GRB7	0.006	0.24	-10000	0	-1.1	20	20
NFKB1	0.027	0.005	-10000	0	-10000	0	0
MAPK8	-0.006	0.23	-10000	0	-1.1	20	20
PI3K	-0.006	0.22	-10000	0	-0.97	21	21
FES	0.004	0.24	-10000	0	-1	22	22
Crk/Dok-R	0.017	0.23	-10000	0	-1	21	21
Tie2/Ang1/ABIN2	0.008	0.24	-10000	0	-1.1	21	21
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.023	0.18	0.39	1	-0.75	21	22
STAT5A	0.028	0.003	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.043	0.2	0.42	5	-0.79	20	25
Tie2/Ang2	0.011	0.21	-10000	0	-0.88	18	18
Tie2/Ang1	-0.004	0.25	-10000	0	-1.1	21	21
FOXO1	0.024	0.18	-10000	0	-0.76	20	20
ELF1	0.028	0.045	-10000	0	-0.47	3	3
ELF2	-0.002	0.22	-10000	0	-1.1	20	20
mol:Choline	-0.003	0.21	-10000	0	-0.99	21	21
cell migration	-0.043	0.06	-10000	0	-0.22	22	22
FYN	0.015	0.19	-10000	0	-0.74	18	18
DOK2	0.022	0.039	-10000	0	-0.41	4	4
negative regulation of cell cycle	0.032	0.15	0.39	2	-0.55	15	17
ETS1	0.023	0.054	-10000	0	-0.28	15	15
PXN	0.046	0.18	0.38	9	-0.66	20	29
ITGB1	0.027	0.005	-10000	0	-10000	0	0
NOS3	0.023	0.18	0.43	2	-0.71	21	23
RAC1	0.026	0.007	-10000	0	-10000	0	0
TNF	0.008	0.098	-10000	0	-0.34	35	35
MAPKKK cascade	-0.003	0.21	-10000	0	-0.99	21	21
RASA1	0.024	0.031	-10000	0	-0.46	2	2
Tie2/Ang1/Shc	0.008	0.24	-10000	0	-1.1	21	21
NCK1	0.023	0.011	-10000	0	-10000	0	0
vasculogenesis	0.027	0.15	0.38	3	-0.56	21	24
mol:Phosphatidic acid	-0.003	0.21	-10000	0	-0.99	21	21
mol:Angiotensin II	0	0.004	-10000	0	-10000	0	0
mol:NADP	0.025	0.16	0.39	3	-0.62	21	24
Rac1/GTP	0.021	0.18	-10000	0	-0.75	21	21
MMP2	-0.025	0.23	-10000	0	-1	21	21

×

PDGFR-beta signaling 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0	0.093	-10000	0	-0.36	9	9
PDGFB-D/PDGFRB/SLAP	-0.015	0.11	-10000	0	-0.27	81	81
PDGFB-D/PDGFRB/APS/CBL	0.005	0.1	-10000	0	-0.22	79	79
AKT1	0.026	0.12	0.36	16	-0.34	1	17
mol:PI-4-5-P2	0	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.009	0.11	0.28	10	-0.4	10	20
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
FGR	-0.015	0.11	0.34	1	-0.47	13	14
mol:Ca2+	0.002	0.12	0.27	12	-0.39	20	32
MYC	0.058	0.13	0.4	27	-10000	0	27
SHC1	0.028	0.004	-10000	0	-10000	0	0
HRAS/GDP	0.007	0.089	-10000	0	-0.24	1	1
LRP1/PDGFRB/PDGFB	0.005	0.11	-10000	0	-0.24	82	82
GRB10	0.026	0.007	-10000	0	-10000	0	0
PTPN11	0.028	0.002	-10000	0	-10000	0	0
GO:0007205	0.001	0.12	0.28	9	-0.4	20	29
PTEN	0.027	0.006	-10000	0	-10000	0	0
GRB2	0.027	0.004	-10000	0	-10000	0	0
GRB7	0.025	0.038	-10000	0	-0.46	3	3
PDGFB-D/PDGFRB/SHP2	-0.011	0.11	-10000	0	-0.27	85	85
PDGFB-D/PDGFRB/GRB10	-0.01	0.11	-10000	0	-0.27	80	80
cell cycle arrest	-0.015	0.11	-10000	0	-0.27	81	81
HRAS	0.026	0.02	-10000	0	-0.4	1	1
HIF1A	0.021	0.11	0.35	14	-10000	0	14
GAB1	0.006	0.11	0.3	5	-0.39	10	15
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	0.007	0.1	0.3	8	-0.38	5	13
PDGFB-D/PDGFRB	0.006	0.1	-10000	0	-0.22	78	78
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	-0.011	0.11	-10000	0	-0.27	85	85
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0	0.079	-10000	0	-0.38	2	2
positive regulation of MAPKKK cascade	-0.011	0.11	-10000	0	-0.27	85	85
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
mol:IP3	0.002	0.12	0.29	9	-0.4	20	29
E5	0	0.001	-10000	0	-10000	0	0
CSK	0.027	0.006	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.012	0.12	-10000	0	-0.27	85	85
SHB	0.025	0.009	-10000	0	-10000	0	0
BLK	-0.058	0.15	-10000	0	-0.48	43	43
PTPN2	0.026	0.008	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SNX15	-0.011	0.11	-10000	0	-0.27	83	83
BCAR1	0.027	0.006	-10000	0	-10000	0	0
VAV2	0.012	0.11	0.33	9	-0.41	8	17
CBL	0.025	0.008	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/DEP1	-0.01	0.11	-10000	0	-0.27	83	83
LCK	-0.016	0.1	0.34	1	-0.48	12	13
PDGFRB	-0.04	0.15	-10000	0	-0.38	85	85
ACP1	0.028	0.003	-10000	0	-10000	0	0
HCK	-0.007	0.09	-10000	0	-0.76	3	3
ABL1	0.004	0.11	0.27	14	-0.41	8	22
PDGFB-D/PDGFRB/CBL	0.003	0.12	0.36	2	-0.42	17	19
PTPN1	0.027	0.007	-10000	0	-10000	0	0
SNX15	0.027	0.006	-10000	0	-10000	0	0
STAT3	0.028	0.003	-10000	0	-10000	0	0
STAT1	0.009	0.084	-10000	0	-0.39	22	22
cell proliferation	0.057	0.12	0.38	31	-10000	0	31
SLA	0.021	0.033	-10000	0	-0.39	3	3
actin cytoskeleton reorganization	0.032	0.11	0.34	10	-10000	0	10
SRC	-0.01	0.1	-10000	0	-0.66	6	6
PI3K	-0.015	0.064	-10000	0	-0.35	2	2
PDGFB-D/PDGFRB/GRB7/SHC	0.006	0.11	-10000	0	-0.23	84	84
SH2B2	0.025	0.02	-10000	0	-0.39	1	1
PLCgamma1/SPHK1	0.009	0.12	0.29	9	-0.42	10	19
LYN	-0.006	0.071	-10000	0	-10000	0	0
LRP1	0.027	0.022	-10000	0	-0.46	1	1
SOS1	0.028	0.004	-10000	0	-10000	0	0
STAT5B	0.028	0.003	-10000	0	-10000	0	0
STAT5A	0.028	0.003	-10000	0	-10000	0	0
NCK1-2/p130 Cas	0.024	0.089	-10000	0	-10000	0	0
SPHK1	0.017	0.067	-10000	0	-0.38	14	14
EDG1	0	0.003	-10000	0	-10000	0	0
mol:DAG	0.002	0.12	0.29	9	-0.4	20	29
PLCG1	0.001	0.12	0.29	9	-0.41	20	29
NHERF/PDGFRB	0.006	0.11	-10000	0	-0.23	77	77
YES1	-0.017	0.094	0.35	1	-0.54	8	9
cell migration	0.005	0.11	-10000	0	-0.23	77	77
SHC/Grb2/SOS1	0.032	0.095	-10000	0	-10000	0	0
SLC9A3R2	0.027	0.019	-10000	0	-0.39	1	1
SLC9A3R1	0.024	0.043	-10000	0	-0.46	4	4
NHERF1-2/PDGFRB/PTEN	0.018	0.1	-10000	0	-0.38	4	4
FYN	-0.012	0.091	-10000	0	-0.43	4	4
DOK1	-0.006	0.093	-10000	0	-10000	0	0
HRAS/GTP	0.019	0.014	-10000	0	-0.28	1	1
PDGFB	0.022	0.048	-10000	0	-0.39	7	7
RAC1	0.025	0.11	0.36	12	-0.42	4	16
PRKCD	-0.007	0.09	0.19	9	-10000	0	9
FER	-0.005	0.093	-10000	0	-10000	0	0
MAPKKK cascade	-0.014	0.094	0.36	7	-10000	0	7
RASA1	-0.005	0.095	-10000	0	-0.26	2	2
NCK1	0.023	0.011	-10000	0	-10000	0	0
NCK2	0.028	0.003	-10000	0	-10000	0	0
p62DOK/Csk	0.007	0.091	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SHB	-0.012	0.11	-10000	0	-0.26	82	82
chemotaxis	0.004	0.1	0.27	14	-0.4	8	22
STAT1-3-5/STAT1-3-5	0.011	0.1	-10000	0	-0.35	6	6
Bovine Papilomavirus E5/PDGFRB	-0.027	0.11	-10000	0	-0.26	85	85
PTPRJ	0.027	0.005	-10000	0	-10000	0	0

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	-0.001	0.11	0.32	49	-10000	0	49
KIRREL	0.002	0.1	-10000	0	-0.46	23	23
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.001	0.11	-10000	0	-0.32	49	49
PLCG1	0.027	0.006	-10000	0	-10000	0	0
ARRB2	0.027	0.006	-10000	0	-10000	0	0
WASL	0.027	0.006	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	0.024	0.097	-10000	0	-0.3	24	24
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.002	0.062	-10000	0	-0.26	16	16
FYN	-0.016	0.084	0.27	9	-0.28	24	33
mol:Ca2+	0.022	0.094	-10000	0	-0.3	22	22
mol:DAG	0.023	0.095	-10000	0	-0.3	22	22
NPHS2	-0.013	0.068	-10000	0	-0.4	13	13
mol:IP3	0.023	0.095	-10000	0	-0.3	22	22
regulation of endocytosis	0.021	0.084	-10000	0	-0.27	21	21
Nephrin/NEPH1/podocin/Cholesterol	0.011	0.092	-10000	0	-0.24	54	54
establishment of cell polarity	0.001	0.11	-10000	0	-0.32	49	49
Nephrin/NEPH1/podocin/NCK1-2	0.032	0.09	-10000	0	-0.32	12	12
Nephrin/NEPH1/beta Arrestin2	0.023	0.085	-10000	0	-0.28	21	21
NPHS1	-0.02	0.098	-10000	0	-0.4	30	30
Nephrin/NEPH1/podocin	0.015	0.085	-10000	0	-0.28	24	24
TJP1	0.028	0.004	-10000	0	-10000	0	0
NCK1	0.023	0.011	-10000	0	-10000	0	0
NCK2	0.028	0.003	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.024	0.096	-10000	0	-0.3	22	22
CD2AP	0.027	0.006	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	0.025	0.098	-10000	0	-0.3	24	24
GRB2	0.027	0.004	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.026	0.092	0.28	7	-0.26	36	43
cytoskeleton organization	-0.01	0.071	0.23	3	-0.3	18	21
Nephrin/NEPH1	0.006	0.076	-10000	0	-0.22	48	48
Nephrin/NEPH1/ZO-1	0.02	0.091	-10000	0	-0.29	23	23

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.05	0.063	0.32	1	-10000	0	1
SMARCC2	0.029	0.009	-10000	0	-10000	0	0
SMARCC1	0.025	0.012	-10000	0	-10000	0	0
TBX21	-0.083	0.16	-10000	0	-0.55	35	35
SUMO2	0.027	0.011	-10000	0	-10000	0	0
STAT1 (dimer)	0.015	0.084	-10000	0	-0.38	22	22
FKBP4	0.026	0.008	-10000	0	-10000	0	0
FKBP5	0.024	0.036	-10000	0	-0.44	3	3
GR alpha/HSP90/FKBP51/HSP90	0.087	0.08	0.31	18	-0.25	1	19
PRL	-0.077	0.13	-10000	0	-0.59	6	6
cortisol/GR alpha (dimer)/TIF2	0.11	0.18	0.54	38	-0.34	1	39
RELA	-0.011	0.09	-10000	0	-0.25	15	15
FGG	0.074	0.17	0.46	26	-0.36	19	45
GR beta/TIF2	0.052	0.12	0.32	18	-0.29	26	44
IFNG	-0.2	0.2	-10000	0	-0.61	50	50
apoptosis	0.016	0.15	0.49	9	-0.56	10	19
CREB1	0.029	0.015	-10000	0	-10000	0	0
histone acetylation	-0.006	0.098	0.3	10	-0.38	7	17
BGLAP	-0.041	0.094	-10000	0	-0.49	4	4
GR/PKAc	0.1	0.077	0.32	13	-0.29	1	14
NF kappa B1 p50/RelA	-0.02	0.15	-10000	0	-0.4	29	29
SMARCD1	0.029	0.008	-10000	0	-10000	0	0
MDM2	0.052	0.065	0.24	27	-10000	0	27
GATA3	0.013	0.084	-10000	0	-0.4	20	20
AKT1	0.021	0.006	-10000	0	-10000	0	0
CSF2	-0.14	0.14	-10000	0	-0.49	17	17
GSK3B	0.024	0.013	-10000	0	-10000	0	0
NR1I3	0.023	0.15	0.47	8	-0.66	4	12
CSN2	0.073	0.12	0.39	19	-10000	0	19
BRG1/BAF155/BAF170/BAF60A	0.065	0.037	-10000	0	-0.4	1	1
NFATC1	0.025	0.01	-10000	0	-10000	0	0
POU2F1	0.028	0.014	-10000	0	-10000	0	0
CDKN1A	0.016	0.05	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0	0.006	-10000	0	-10000	0	0
SFN	0.024	0.04	-10000	0	-0.42	4	4
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.095	0.081	0.34	10	-10000	0	10
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.002	0.21	0.45	8	-0.8	25	33
JUN	-0.15	0.13	-10000	0	-0.49	32	32
IL4	-0.049	0.089	-10000	0	-0.48	5	5
CDK5R1	0.026	0.026	-10000	0	-0.39	2	2
PRKACA	0.028	0.004	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.099	0.2	0.19	2	-0.41	96	98
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.097	0.08	0.32	16	-10000	0	16
cortisol/GR alpha (monomer)	0.17	0.21	0.62	48	-10000	0	48
NCOA2	-0.009	0.12	-10000	0	-0.46	36	36
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.11	0.15	-10000	0	-0.51	63	63
AP-1/NFAT1-c-4	-0.24	0.19	-10000	0	-0.6	62	62
AFP	-0.1	0.13	-10000	0	-0.61	10	10
SUV420H1	0.026	0.008	-10000	0	-10000	0	0
IRF1	0.083	0.11	0.46	8	-10000	0	8
TP53	0.038	0.044	-10000	0	-0.45	4	4
PPP5C	0.027	0.005	-10000	0	-10000	0	0
KRT17	-0.21	0.23	-10000	0	-0.71	46	46
KRT14	-0.16	0.31	-10000	0	-1.2	38	38
TBP	0.033	0.017	-10000	0	-10000	0	0
CREBBP	0.066	0.074	0.32	29	-0.34	1	30
HDAC1	0.027	0.007	-10000	0	-10000	0	0
HDAC2	0.042	0.017	-10000	0	-10000	0	0
AP-1	-0.24	0.19	-10000	0	-0.61	62	62
MAPK14	0.026	0.011	-10000	0	-10000	0	0
MAPK10	0	0.11	-10000	0	-0.45	27	27
MAPK11	0.026	0.011	-10000	0	-10000	0	0
KRT5	-0.16	0.19	-10000	0	-0.78	21	21
interleukin-1 receptor activity	0.015	0.016	-10000	0	-10000	0	0
NCOA1	0.03	0.004	-10000	0	-10000	0	0
STAT1	0.015	0.084	-10000	0	-0.38	22	22
CGA	-0.048	0.093	-10000	0	-0.49	6	6
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.15	0.14	0.37	69	-0.33	1	70
MAPK3	0.027	0.011	-10000	0	-10000	0	0
MAPK1	0.026	0.011	-10000	0	-10000	0	0
ICAM1	-0.089	0.17	-10000	0	-0.55	27	27
NFKB1	-0.012	0.094	-10000	0	-0.27	16	16
MAPK8	-0.12	0.12	-10000	0	-0.47	30	30
MAPK9	0.026	0.011	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.016	0.16	0.5	9	-0.59	10	19
BAX	0.016	0.051	-10000	0	-10000	0	0
POMC	-0.11	0.25	-10000	0	-1.4	13	13
EP300	0.064	0.074	0.32	27	-0.35	2	29
cortisol/GR alpha (dimer)/p53	0.16	0.18	0.56	41	-0.39	1	42
proteasomal ubiquitin-dependent protein catabolic process	0.029	0.054	0.24	10	-10000	0	10
SGK1	0.07	0.12	0.55	2	-1.1	2	4
IL13	-0.14	0.15	-10000	0	-0.67	12	12
IL6	-0.13	0.3	-10000	0	-0.91	54	54
PRKACG	-0.008	0.019	-10000	0	-10000	0	0
IL5	-0.12	0.12	-10000	0	-0.6	8	8
IL2	-0.16	0.16	-10000	0	-0.63	21	21
CDK5	0.027	0.008	-10000	0	-10000	0	0
PRKACB	0.026	0.022	-10000	0	-0.46	1	1
HSP90AA1	0.026	0.007	-10000	0	-10000	0	0
IL8	-0.12	0.21	-10000	0	-0.64	35	35
CDK5R1/CDK5	0.038	0.023	-10000	0	-0.27	2	2
NF kappa B1 p50/RelA/PKAc	0.011	0.13	-10000	0	-0.34	13	13
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.14	0.17	0.52	46	-10000	0	46
SMARCA4	0.028	0.009	-10000	0	-10000	0	0
chromatin remodeling	0.087	0.1	0.36	25	-0.48	1	26
NF kappa B1 p50/RelA/Cbp	0.054	0.16	0.39	12	-0.38	10	22
JUN (dimer)	-0.15	0.13	-10000	0	-0.49	32	32
YWHAH	0.027	0.004	-10000	0	-10000	0	0
VIPR1	-0.072	0.16	-10000	0	-0.74	20	20
NR3C1	0.099	0.13	0.42	36	-10000	0	36
NR4A1	-0.004	0.11	-10000	0	-0.47	20	20
TIF2/SUV420H1	0.011	0.09	-10000	0	-0.33	32	32
MAPKKK cascade	0.016	0.15	0.49	9	-0.56	10	19
cortisol/GR alpha (dimer)/Src-1	0.16	0.18	0.54	51	-10000	0	51
PBX1	-0.059	0.19	-10000	0	-0.46	91	91
POU1F1	-0.001	0.023	-10000	0	-10000	0	0
SELE	-0.17	0.35	-10000	0	-0.95	75	75
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.087	0.1	0.36	24	-0.49	1	25
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.14	0.17	0.52	46	-10000	0	46
mol:cortisol	0.082	0.12	0.36	47	-10000	0	47
MMP1	-0.34	0.16	-10000	0	-0.69	47	47

×

Wnt signaling

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
Noncanonical Wnts/FZD	-0.017	0.11	-9999	-0.5	12	12
FZD6	0.023	0.024	-9999	-0.46	1	1
WNT6	-0.009	0.12	-9999	-0.4	43	43
WNT4	0.013	0.079	-9999	-0.44	15	15
FZD3	0.019	0.057	-9999	-0.46	7	7
WNT5A	0.019	0.052	-9999	-0.45	6	6
WNT11	-0.019	0.13	-9999	-0.41	52	52

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.026	0.022	-10000	0	-0.46	1	1
HDAC4	0.027	0.006	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.002	0.062	0.28	25	-10000	0	25
CDKN1A	-0.006	0.011	-10000	0	-10000	0	0
KAT2B	0.007	0.092	-10000	0	-0.46	19	19
BAX	0.027	0.004	-10000	0	-10000	0	0
FOXO3	-0.005	0.018	0.38	1	-10000	0	1
FOXO1	0.026	0.007	-10000	0	-10000	0	0
FOXO4	0.015	0.021	-10000	0	-0.26	3	3
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.027	0.004	-10000	0	-10000	0	0
TAT	0.002	0.048	-10000	0	-0.39	6	6
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.057	0.13	-10000	0	-0.34	87	87
PPARGC1A	-0.13	0.23	-10000	0	-0.46	166	166
FHL2	0.026	0.031	-10000	0	-0.46	2	2
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.037	0.018	-10000	0	-0.33	1	1
HIST2H4A	-0.002	0.062	-10000	0	-0.28	25	25
SIRT1/FOXO3a	0.013	0.029	0.27	1	-0.21	6	7
SIRT1	0.023	0.022	-10000	0	-0.46	1	1
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.05	0.021	-10000	0	-0.28	1	1
SIRT1/Histone H1b	0.018	0.047	-10000	0	-0.21	8	8
apoptosis	-0.05	0.02	0.28	1	-10000	0	1
SIRT1/PGC1A	-0.071	0.15	-10000	0	-0.28	165	165
p53/SIRT1	0.026	0.036	-10000	0	-0.33	5	5
SIRT1/FOXO4	0.026	0.034	-10000	0	-0.23	4	4
FOXO1/FHL2/SIRT1	0.046	0.027	-10000	0	-0.26	3	3
HIST1H1E	0.009	0.035	-10000	0	-0.25	4	4
SIRT1/p300	0.036	0.024	-10000	0	-0.33	2	2
muscle cell differentiation	0.028	0.12	0.29	93	-10000	0	93
TP53	0.019	0.043	-10000	0	-0.46	4	4
KU70/SIRT1/BAX	0.051	0.02	-10000	0	-0.28	1	1
CREBBP	0.027	0.004	-10000	0	-10000	0	0
MEF2D	0.028	0.004	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.029	0.038	-10000	0	-0.28	7	7
ACSS2	0.011	0.016	-10000	0	-0.33	1	1
SIRT1/PCAF/MYOD	-0.028	0.12	-10000	0	-0.29	93	93

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.096	0.21	-10000	0	-0.46	128	128
oxygen homeostasis	0	0	-10000	0	-10000	0	0
TCEB2	0.026	0.026	-10000	0	-0.39	2	2
TCEB1	0.025	0.009	-10000	0	-10000	0	0
HIF1A/p53	0.024	0.065	0.26	4	-0.28	11	15
HIF1A	0.005	0.044	-10000	0	-0.27	10	10
COPS5	0.025	0.009	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.063	0.036	-10000	0	-10000	0	0
FIH (dimer)	0.027	0.004	-10000	0	-10000	0	0
CDKN2A	-0.13	0.19	-10000	0	-0.39	187	187
ARNT/IPAS	-0.05	0.16	-10000	0	-0.33	124	124
HIF1AN	0.027	0.004	-10000	0	-10000	0	0
GNB2L1	0.026	0.007	-10000	0	-10000	0	0
HIF1A/ARNT	0.024	0.059	0.26	3	-0.27	11	14
CUL2	0.027	0.005	-10000	0	-10000	0	0
OS9	0.028	0.004	-10000	0	-10000	0	0
RACK1/Elongin B/Elongin C	0.047	0.022	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF1A/Hsp90	0.021	0.054	0.26	1	-0.27	11	12
PHD1-3/OS9	0.05	0.064	-10000	0	-0.26	5	5
HIF1A/RACK1/Elongin B/Elongin C	0.04	0.058	0.26	1	-0.33	2	3
VHL	0.025	0.009	-10000	0	-10000	0	0
HSP90AA1	0.026	0.007	-10000	0	-10000	0	0
HIF1A/JAB1	0.021	0.055	0.26	1	-0.27	10	11
EGLN3	0.004	0.096	-10000	0	-0.4	27	27
EGLN2	0.027	0.005	-10000	0	-10000	0	0
EGLN1	0.027	0.004	-10000	0	-10000	0	0
TP53	0.023	0.043	-10000	0	-0.46	4	4
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	-0.013	0.17	-10000	0	-0.49	49	49
ARNT	0.027	0.004	-10000	0	-10000	0	0
ARD1A	0	0	-10000	0	-10000	0	0
RBX1	0.027	0.004	-10000	0	-10000	0	0
HIF1A/p19ARF	-0.054	0.1	-10000	0	-0.32	14	14

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.005	0.081	-10000	0	-10000	0	0
epithelial cell differentiation	-0.028	0.1	-10000	0	-0.4	2	2
ITCH	0.038	0.02	-10000	0	-10000	0	0
WWP1	-0.004	0.077	-10000	0	-10000	0	0
FYN	0.027	0.019	-10000	0	-0.39	1	1
EGFR	0.02	0.044	-10000	0	-0.46	4	4
PRL	-0.007	0.044	-10000	0	-0.39	5	5
neuron projection morphogenesis	-0.018	0.094	0.27	3	-10000	0	3
PTPRZ1	0.007	0.095	-10000	0	-0.46	20	20
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.003	0.11	-10000	0	-10000	0	0
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.035	0.095	-10000	0	-0.38	2	2
ADAM17	0.039	0.036	-10000	0	-0.45	2	2
ErbB4/ErbB4	-0.019	0.08	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.011	0.087	-10000	0	-0.38	1	1
NCOR1	0.027	0.006	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.023	0.099	-10000	0	-0.36	3	3
GRIN2B	-0.028	0.097	0.27	3	-0.35	3	6
ErbB4/ErbB2/betacellulin	-0.07	0.13	-10000	0	-0.32	35	35
STAT1	0.009	0.084	-10000	0	-0.39	22	22
HBEGF	0.027	0.006	-10000	0	-10000	0	0
PRLR	-0.061	0.18	-10000	0	-0.46	90	90
E4ICDs/ETO2	-0.005	0.082	-10000	0	-10000	0	0
axon guidance	-0.007	0.073	0.38	1	-10000	0	1
NEDD4	0.04	0.019	-10000	0	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	-0.035	0.14	-10000	0	-0.34	91	91
CBFA2T3	0.026	0.022	-10000	0	-0.46	1	1
ErbB4/ErbB2/HBEGF	0.009	0.066	-10000	0	-10000	0	0
MAPK3	-0.015	0.098	0.27	3	-10000	0	3
STAT1 (dimer)	-0.014	0.095	-10000	0	-10000	0	0
MAPK1	-0.015	0.097	0.27	3	-10000	0	3
JAK2	0.024	0.01	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.029	0.094	-10000	0	-0.36	2	2
NRG1	-0.023	0.1	-10000	0	-0.28	75	75
NRG3	0.002	0.053	-10000	0	-0.44	6	6
NRG2	-0.24	0.24	-10000	0	-0.46	274	274
NRG4	-0.004	0.12	-10000	0	-0.46	31	31
heart development	-0.007	0.073	0.38	1	-10000	0	1
neural crest cell migration	-0.029	0.093	-10000	0	-0.36	2	2
ERBB2	0.021	0.025	-10000	0	-0.31	2	2
WWOX/E4ICDs	-0.004	0.079	-10000	0	-10000	0	0
SHC1	0.028	0.004	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.011	0.1	-10000	0	-0.36	12	12
apoptosis	0.03	0.1	0.57	5	-10000	0	5
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.15	0.16	-10000	0	-0.38	74	74
ErbB4/ErbB2/epiregulin	-0.052	0.13	-10000	0	-0.33	28	28
ErbB4/ErbB4/betacellulin/betacellulin	-0.09	0.15	-10000	0	-0.38	42	42
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.025	0.12	-10000	0	-0.44	2	2
MDM2	-0.009	0.081	0.36	2	-10000	0	2
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.02	0.086	-10000	0	-0.33	1	1
STAT5A	-0.006	0.07	0.34	1	-10000	0	1
ErbB4/EGFR/neuregulin 1 beta	-0.025	0.096	-10000	0	-0.35	2	2
DLG4	0.026	0.022	-10000	0	-0.46	1	1
GRB2/SHC	0.04	0.008	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.006	0.075	-10000	0	-10000	0	0
STAT5A (dimer)	-0.024	0.12	-10000	0	-0.43	2	2
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.005	0.082	0.33	1	-10000	0	1
LRIG1	0.016	0.065	-10000	0	-0.46	9	9
EREG	-0.097	0.21	-10000	0	-0.46	131	131
BTC	-0.13	0.22	-10000	0	-0.46	159	159
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.007	0.071	0.38	1	-10000	0	1
ERBB4	-0.021	0.073	-10000	0	-10000	0	0
STAT5B	0.028	0.003	-10000	0	-10000	0	0
YAP1	-0.014	0.1	-10000	0	-0.43	28	28
GRB2	0.027	0.004	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.005	0.09	-10000	0	-0.42	1	1
glial cell differentiation	0.006	0.075	-10000	0	-10000	0	0
WWOX	0.025	0.008	-10000	0	-10000	0	0
cell proliferation	-0.096	0.16	0.31	1	-0.44	33	34

×

Syndecan-3-mediated signaling events

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
CTTN	0.02	0.013	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.037	0.12	-9999	-0.38	7	7
Syndecan-3/Neurocan	0.012	0.074	-9999	-0.36	12	12
POMC	-0.025	0.14	-9999	-0.4	63	63
EGFR	0.02	0.044	-9999	-0.46	4	4
Syndecan-3/EGFR	0.018	0.064	-9999	-0.36	11	11
AGRP	-0.002	0.022	-9999	-10000	0	0
NCSTN	0.027	0.004	-9999	-10000	0	0
PSENEN	0.027	0.005	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.028	0.004	-9999	-10000	0	0
APH1A	0.027	0.005	-9999	-10000	0	0
NCAN	-0.005	0.089	-9999	-0.39	25	25
long-term memory	0.026	0.059	-9999	-0.35	9	9
Syndecan-3/IL8	-0.019	0.1	-9999	-0.4	14	14
PSEN1	0.027	0.006	-9999	-10000	0	0
Src/Cortactin	0.028	0.02	-9999	-10000	0	0
FYN	0.027	0.019	-9999	-0.39	1	1
limb bud formation	0.004	0.061	-9999	-0.37	13	13
MC4R	0.002	0.028	-9999	-0.39	1	1
SRC	0.026	0.007	-9999	-10000	0	0
PTN	-0.15	0.24	-9999	-0.46	186	186
FGFR/FGF/Syndecan-3	0.004	0.062	-9999	-0.38	13	13
neuron projection morphogenesis	-0.033	0.13	-9999	-0.35	9	9
Syndecan-3/AgRP	0.017	0.063	-9999	-0.36	13	13
Syndecan-3/AgRP/MC4R	0.028	0.064	-9999	-0.34	13	13
Fyn/Cortactin	0.029	0.019	-9999	-10000	0	0
SDC3	0.004	0.062	-9999	-0.38	13	13
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.019	0.1	-9999	-0.4	14	14
IL8	-0.059	0.17	-9999	-0.39	106	106
Syndecan-3/Fyn/Cortactin	0.027	0.06	-9999	-0.35	9	9
Syndecan-3/CASK	0.003	0.059	-9999	-0.36	13	13
alpha-MSH/MC4R	-0.006	0.11	-9999	-0.28	63	63
Gamma Secretase	0.075	0.026	-9999	-10000	0	0

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.027	0.038	-10000	0	-0.38	3	3
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.054	0.13	0.5	17	-10000	0	17
IL27/IL27R/JAK1	-0.039	0.15	-10000	0	-0.53	12	12
TBX21	-0.089	0.17	-10000	0	-0.52	32	32
IL12B	-0.013	0.12	-10000	0	-0.39	44	44
IL12A	-0.007	0.055	-10000	0	-0.32	15	15
IL6ST	-0.039	0.16	-10000	0	-0.47	60	60
IL27RA/JAK1	-0.005	0.067	-10000	0	-10000	0	0
IL27	-0.004	0.088	-10000	0	-0.4	23	23
TYK2	0.017	0.028	-10000	0	-0.4	1	1
T-helper cell lineage commitment	0.003	0.11	-10000	0	-0.57	1	1
T-helper 2 cell differentiation	0.054	0.13	0.5	17	-10000	0	17
T cell proliferation during immune response	0.054	0.13	0.5	17	-10000	0	17
MAPKKK cascade	-0.054	0.13	-10000	0	-0.5	17	17
STAT3	0.028	0.003	-10000	0	-10000	0	0
STAT2	0.028	0.003	-10000	0	-10000	0	0
STAT1	0.008	0.085	-10000	0	-0.39	22	22
IL12RB1	-0.003	0.11	-10000	0	-0.39	37	37
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.12	0.19	-10000	0	-0.5	48	48
IL27/IL27R/JAK2/TYK2	-0.055	0.14	-10000	0	-0.51	17	17
positive regulation of T cell mediated cytotoxicity	-0.054	0.13	-10000	0	-0.5	17	17
STAT1 (dimer)	-0.081	0.2	0.52	1	-0.63	20	21
JAK2	0.017	0.019	-10000	0	-10000	0	0
JAK1	0.027	0.005	-10000	0	-10000	0	0
STAT2 (dimer)	-0.044	0.14	-10000	0	-0.48	17	17
T cell proliferation	-0.068	0.14	-10000	0	-0.5	25	25
IL12/IL12R/TYK2/JAK2	-0.05	0.19	-10000	0	-0.75	27	27
IL17A	0.003	0.11	-10000	0	-0.57	1	1
mast cell activation	0.054	0.13	0.5	17	-10000	0	17
IFNG	-0.011	0.038	-10000	0	-0.098	15	15
T cell differentiation	-0.005	0.007	-10000	0	-0.019	62	62
STAT3 (dimer)	-0.044	0.14	-10000	0	-0.48	17	17
STAT5A (dimer)	-0.044	0.14	-10000	0	-0.48	17	17
STAT4 (dimer)	-0.047	0.14	-10000	0	-0.5	19	19
STAT4	0.016	0.066	-10000	0	-0.39	13	13
T cell activation	-0.005	0.012	0.05	19	-10000	0	19
IL27R/JAK2/TYK2	-0.021	0.12	-10000	0	-0.54	3	3
GATA3	-0.004	0.12	0.6	4	-1.3	3	7
IL18	-0.002	0.051	-10000	0	-0.33	12	12
positive regulation of mast cell cytokine production	-0.043	0.14	-10000	0	-0.48	17	17
IL27/EBI3	0.006	0.083	-10000	0	-0.3	31	31
IL27RA	-0.012	0.067	-10000	0	-10000	0	0
IL6	-0.014	0.14	-10000	0	-0.45	46	46
STAT5A	0.028	0.003	-10000	0	-10000	0	0
monocyte differentiation	-0.001	0.002	-10000	0	-10000	0	0
IL2	-0.001	0.047	-10000	0	-10000	0	0
IL1B	-0.022	0.085	-10000	0	-0.28	52	52
EBI3	0.013	0.061	-10000	0	-0.42	9	9
TNF	-0.006	0.059	-10000	0	-0.28	23	23

×

Ceramide 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
SPHK2	0.012	0.022	-10000	0	-0.27	3	3
MAP4K4	0.019	0.064	0.21	3	-0.39	5	8
BAG4	0.023	0.023	-10000	0	-0.46	1	1
PKC zeta/ceramide	-0.009	0.068	-10000	0	-0.21	35	35
NFKBIA	0.026	0.007	-10000	0	-10000	0	0
BIRC3	0.012	0.071	-10000	0	-0.39	15	15
BAX	-0.004	0.053	-10000	0	-0.34	10	10
RIPK1	0.027	0.006	-10000	0	-10000	0	0
AKT1	0.023	0.13	0.69	19	-10000	0	19
BAD	-0.019	0.068	0.2	10	-0.21	33	43
SMPD1	0.019	0.067	0.18	24	-0.23	11	35
RB1	-0.023	0.062	0.2	1	-0.22	32	33
FADD/Caspase 8	0.057	0.1	0.26	32	-0.4	3	35
MAP2K4	-0.021	0.059	0.18	4	-0.27	9	13
NSMAF	0.025	0.009	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.02	0.061	0.18	7	-0.26	11	18
EGF	-0.067	0.19	-10000	0	-0.46	98	98
mol:ceramide	-0.023	0.065	-10000	0	-0.22	34	34
MADD	0.027	0.005	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.011	0.022	-10000	0	-0.26	3	3
ASAH1	0.026	0.008	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.023	0.061	0.19	1	-0.21	32	33
cell proliferation	-0.03	0.097	-10000	0	-0.28	20	20
BID	0.01	0.11	-10000	0	-0.64	9	9
MAP3K1	-0.022	0.061	0.19	2	-0.21	33	35
EIF2A	0.021	0.1	0.19	95	-0.26	9	104
TRADD	0.027	0.006	-10000	0	-10000	0	0
CRADD	0.028	0.002	-10000	0	-10000	0	0
MAPK3	-0.015	0.061	0.18	1	-0.28	6	7
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.014	0.062	0.18	2	-0.28	7	9
Cathepsin D/ceramide	-0.008	0.068	-10000	0	-0.21	34	34
FADD	0.044	0.082	0.21	43	-0.42	2	45
KSR1	-0.021	0.065	0.19	5	-0.21	34	39
MAPK8	-0.018	0.071	-10000	0	-0.27	16	16
PRKRA	-0.017	0.069	0.19	14	-0.21	31	45
PDGFA	0.023	0.032	-10000	0	-0.39	3	3
TRAF2	0.023	0.041	-10000	0	-0.39	5	5
IGF1	-0.053	0.18	-10000	0	-0.46	85	85
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.023	0.064	-10000	0	-0.22	34	34
CTSD	0.027	0.006	-10000	0	-10000	0	0
regulation of nitric oxide biosynthetic process	0.038	0.012	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.031	0.1	-10000	0	-0.3	20	20
PRKCD	0.024	0.009	-10000	0	-10000	0	0
PRKCZ	0.026	0.022	-10000	0	-0.46	1	1
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.011	0.022	-10000	0	-0.26	3	3
RelA/NF kappa B1	0.038	0.012	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.028	0.003	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.015	0.052	-10000	0	-0.38	5	5
TNFR1A/BAG4/TNF-alpha	0.033	0.061	-10000	0	-0.24	21	21
mol:Sphingosine-1-phosphate	0.012	0.022	-10000	0	-0.27	3	3
MAP2K1	-0.019	0.061	0.2	1	-0.27	7	8
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.027	0.006	-10000	0	-10000	0	0
CYCS	0.002	0.048	0.18	3	-0.19	8	11
TNFRSF1A	0.026	0.007	-10000	0	-10000	0	0
NFKB1	0.027	0.005	-10000	0	-10000	0	0
TNFR1A/BAG4	0.033	0.023	-10000	0	-0.33	1	1
EIF2AK2	-0.017	0.068	0.19	15	-0.22	24	39
TNF-alpha/TNFR1A/FAN	0.034	0.06	-10000	0	-0.23	21	21
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.024	0.076	-10000	0	-0.4	11	11
MAP2K2	-0.02	0.059	-10000	0	-0.27	8	8
SMPD3	-0.001	0.097	0.2	4	-0.3	38	42
TNF	0.008	0.088	-10000	0	-0.4	23	23
PKC zeta/PAR4	0.039	0.019	-10000	0	-0.33	1	1
mol:PHOSPHOCHOLINE	0.032	0.087	0.21	85	-0.18	4	89
NF kappa B1/RelA/I kappa B alpha	0.07	0.033	-10000	0	-0.24	1	1
AIFM1	-0.001	0.055	0.17	4	-0.18	11	15
BCL2	0.022	0.039	-10000	0	-0.41	4	4

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.049	0.17	-10000	0	-0.61	23	23
MKNK1	0.028	0.003	-10000	0	-10000	0	0
MAPK14	-0.013	0.095	-10000	0	-0.3	22	22
ATF2/c-Jun	-0.009	0.069	-10000	0	-0.34	4	4
MAPK11	-0.016	0.097	-10000	0	-0.32	14	14
MITF	-0.029	0.12	-10000	0	-0.39	23	23
MAPKAPK5	-0.019	0.1	-10000	0	-0.37	14	14
KRT8	-0.067	0.15	-10000	0	-0.39	49	49
MAPKAPK3	0.024	0.009	-10000	0	-10000	0	0
MAPKAPK2	0.028	0.004	-10000	0	-10000	0	0
p38alpha-beta/CK2	-0.022	0.14	-10000	0	-0.43	23	23
CEBPB	-0.02	0.1	-10000	0	-0.38	15	15
SLC9A1	-0.021	0.1	-10000	0	-0.38	15	15
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	-0.018	0.1	0.24	1	-0.36	15	16
p38alpha-beta/MNK1	0	0.12	-10000	0	-0.35	22	22
JUN	-0.006	0.072	-10000	0	-0.33	4	4
PPARGC1A	-0.12	0.19	-10000	0	-0.48	69	69
USF1	-0.018	0.1	-10000	0	-0.37	14	14
RAB5/GDP/GDI1	-0.004	0.074	-10000	0	-0.28	12	12
NOS2	-0.057	0.19	-10000	0	-0.62	28	28
DDIT3	-0.023	0.1	-10000	0	-0.36	18	18
RAB5A	0.025	0.009	-10000	0	-10000	0	0
HSPB1	-0.014	0.09	0.29	11	-0.31	14	25
p38alpha-beta/HBP1	0	0.12	-10000	0	-0.35	22	22
CREB1	-0.016	0.097	-10000	0	-0.36	14	14
RAB5/GDP	0.018	0.007	-10000	0	-10000	0	0
EIF4E	-0.016	0.093	0.24	1	-0.34	13	14
RPS6KA4	-0.02	0.1	-10000	0	-0.37	14	14
PLA2G4A	-0.03	0.11	-10000	0	-0.36	18	18
GDI1	-0.017	0.097	-10000	0	-0.38	13	13
TP53	-0.032	0.11	-10000	0	-0.41	24	24
RPS6KA5	-0.023	0.1	-10000	0	-0.34	16	16
ESR1	-0.031	0.12	-10000	0	-0.35	32	32
HBP1	0.026	0.007	-10000	0	-10000	0	0
MEF2C	-0.026	0.11	-10000	0	-0.4	16	16
MEF2A	-0.019	0.1	-10000	0	-0.38	13	13
EIF4EBP1	-0.016	0.096	-10000	0	-0.38	12	12
KRT19	-0.13	0.17	-10000	0	-0.44	51	51
ELK4	-0.018	0.1	-10000	0	-0.37	14	14
ATF6	-0.018	0.1	-10000	0	-0.37	14	14
ATF1	-0.016	0.096	-10000	0	-0.37	12	12
p38alpha-beta/MAPKAPK2	0.001	0.12	-10000	0	-0.39	13	13
p38alpha-beta/MAPKAPK3	-0.002	0.11	-10000	0	-0.35	22	22

×

PDGFR-alpha signaling pathway

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
PDGFRA	0.01	0.07	-10000	0	-0.45	10	10
PDGF/PDGFRA/CRKL	0.023	0.055	-10000	0	-0.31	11	11
positive regulation of JUN kinase activity	0.058	0.042	-10000	0	-0.24	6	6
CRKL	0.026	0.019	-10000	0	-0.39	1	1
PDGF/PDGFRA/Caveolin-3	-0.051	0.15	-10000	0	-0.34	105	105
AP1	-0.1	0.3	0.31	2	-0.87	66	68
mol:IP3	-0.001	0.054	-10000	0	-0.32	10	10
PLCG1	-0.001	0.054	-10000	0	-0.32	10	10
PDGF/PDGFRA/alphaV Integrin	0.023	0.055	-10000	0	-0.3	11	11
RAPGEF1	0.027	0.005	-10000	0	-10000	0	0
CRK	0.027	0.006	-10000	0	-10000	0	0
mol:Ca2+	-0.001	0.053	-10000	0	-0.32	10	10
CAV3	-0.086	0.18	-10000	0	-0.46	99	99
CAV1	-0.004	0.11	-10000	0	-0.39	38	38
SHC/Grb2/SOS1	0.06	0.043	-10000	0	-0.25	6	6
PDGF/PDGFRA/Shf	0.019	0.074	-10000	0	-0.35	16	16
FOS	-0.11	0.29	0.32	2	-0.86	66	68
JUN	-0.023	0.025	-10000	0	-10000	0	0
oligodendrocyte development	0.023	0.055	-10000	0	-0.3	11	11
GRB2	0.027	0.004	-10000	0	-10000	0	0
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
mol:DAG	-0.001	0.054	-10000	0	-0.32	10	10
PDGF/PDGFRA	0.01	0.07	-10000	0	-0.45	10	10
actin cytoskeleton reorganization	0.022	0.052	-10000	0	-0.3	10	10
SRF	0.014	0.011	-10000	0	-10000	0	0
SHC1	0.028	0.004	-10000	0	-10000	0	0
PI3K	0.033	0.043	-10000	0	-0.27	6	6
PDGF/PDGFRA/Crk/C3G	0.044	0.046	-10000	0	-0.26	9	9
JAK1	0.003	0.047	-10000	0	-0.31	10	10
ELK1/SRF	0.004	0.046	0.17	1	-0.27	6	7
SHB	0.025	0.009	-10000	0	-10000	0	0
SHF	0.02	0.061	-10000	0	-0.46	8	8
CSNK2A1	0.029	0.02	-10000	0	-10000	0	0
GO:0007205	-0.007	0.053	-10000	0	-0.33	10	10
SOS1	0.028	0.004	-10000	0	-10000	0	0
Ras protein signal transduction	0.058	0.042	-10000	0	-0.24	6	6
PDGF/PDGFRA/SHB	0.022	0.052	-10000	0	-0.3	10	10
PDGF/PDGFRA/Caveolin-1	0.001	0.096	-10000	0	-0.29	48	48
ITGAV	0.025	0.027	-10000	0	-0.39	2	2
ELK1	-0.013	0.053	-10000	0	-0.29	10	10
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
PDGF/PDGFRA/Crk	0.024	0.053	-10000	0	-0.3	10	10
JAK-STAT cascade	0.003	0.047	-10000	0	-0.31	10	10
cell proliferation	0.019	0.073	-10000	0	-0.35	16	16

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.01	0.058	0.89	1	-10000	0	1
VDR	0.026	0.031	-10000	0	-0.46	2	2
FAM120B	0.027	0.005	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.005	0.093	-10000	0	-0.34	9	9
RXRs/LXRs/DNA/Oxysterols	0.014	0.097	-10000	0	-0.39	11	11
MED1	0.028	0.003	-10000	0	-10000	0	0
mol:9cRA	0.003	0.008	-10000	0	-10000	0	0
RARs/THRs/DNA/Src-1	-0.008	0.092	-10000	0	-0.36	4	4
RXRs/NUR77	0.025	0.12	-10000	0	-0.26	60	60
RXRs/PPAR	-0.081	0.13	-10000	0	-0.35	33	33
NCOR2	0.028	0.004	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.019	0.022	-10000	0	-0.33	2	2
RARs/VDR/DNA/Vit D3	0.034	0.083	-10000	0	-0.25	37	37
RARA	0.027	0.004	-10000	0	-10000	0	0
NCOA1	0.028	0.003	-10000	0	-10000	0	0
VDR/VDR/DNA	0.026	0.031	-10000	0	-0.46	2	2
RARs/RARs/DNA/9cRA	0.023	0.076	-10000	0	-0.24	37	37
RARG	0.027	0.022	-10000	0	-0.46	1	1
RPS6KB1	0.016	0.046	0.54	3	-10000	0	3
RARs/THRs/DNA/SMRT	-0.01	0.093	-10000	0	-0.35	5	5
THRA	0.028	0.004	-10000	0	-10000	0	0
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.019	0.022	-10000	0	-0.33	2	2
RXRs/PPAR/9cRA/PGJ2/DNA	0.02	0.1	-10000	0	-0.25	51	51
NR1H4	-0.004	0.027	-10000	0	-0.39	1	1
RXRs/LXRs/DNA	0.041	0.12	-10000	0	-0.36	4	4
NR1H2	0.029	0.015	-10000	0	-10000	0	0
NR1H3	0.024	0.047	-10000	0	-0.38	6	6
RXRs/VDR/DNA/Vit D3	0.027	0.1	-10000	0	-0.24	52	52
NR4A1	0.018	0.068	-10000	0	-0.46	10	10
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	0.002	0.074	-10000	0	-0.25	7	7
RXRG	-0.032	0.16	-10000	0	-0.45	63	63
RXR alpha/CCPG	0.041	0.013	-10000	0	-10000	0	0
RXRA	0.028	0.015	-10000	0	-10000	0	0
RXRB	0.028	0.016	-10000	0	-10000	0	0
THRB	-0.004	0.12	-10000	0	-0.46	30	30
PPARG	-0.13	0.23	-10000	0	-0.46	166	166
PPARD	0.027	0.006	-10000	0	-10000	0	0
TNF	0.001	0.13	-10000	0	-0.8	6	6
mol:Oxysterols	0.003	0.007	-10000	0	-10000	0	0
cholesterol transport	0.014	0.096	-10000	0	-0.38	11	11
PPARA	0.027	0.005	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	-0.01	0.12	-10000	0	-0.46	36	36
RXRs/NUR77/BCL2	-0.012	0.093	-10000	0	-0.24	62	62
SREBF1	0.01	0.088	-10000	0	-0.53	1	1
RXRs/RXRs/DNA/9cRA	0.02	0.1	-10000	0	-0.25	51	51
ABCA1	0.006	0.1	-10000	0	-0.85	3	3
RARs/THRs	0.028	0.11	-10000	0	-0.47	2	2
RXRs/FXR	0.026	0.11	-10000	0	-0.26	50	50
BCL2	0.022	0.039	-10000	0	-0.41	4	4

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.006	0.033	-10000	0	-0.46	1	1
HSPA8	0.027	0.009	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	0.055	0.099	-10000	0	-0.29	14	14
AKT1	0.005	0.047	-10000	0	-10000	0	0
GSC	0.006	0.14	0.4	1	-0.94	4	5
NKX2-5	0	0.009	-10000	0	-10000	0	0
muscle cell differentiation	0.045	0.15	0.39	41	-10000	0	41
SMAD2-3/SMAD4/SP1	-0.004	0.12	-10000	0	-0.32	2	2
SMAD4	0.009	0.047	-10000	0	-10000	0	0
CBFB	0.027	0.006	-10000	0	-10000	0	0
SAP18	0.027	0.007	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.019	0.049	-10000	0	-0.24	6	6
SMAD3/SMAD4/VDR	0.058	0.056	-10000	0	-10000	0	0
MYC	0.028	0.023	-10000	0	-10000	0	0
CDKN2B	-0.37	0.65	-10000	0	-1.5	122	122
AP1	0.007	0.095	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.035	0.082	-10000	0	-0.43	7	7
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.067	0.16	-10000	0	-0.36	91	91
SP3	0.028	0.006	-10000	0	-10000	0	0
CREB1	0.027	0.005	-10000	0	-10000	0	0
FOXH1	-0.023	0.12	-10000	0	-0.39	52	52
SMAD3/SMAD4/GR	0.062	0.065	-10000	0	-10000	0	0
GATA3	0.011	0.084	-10000	0	-0.39	20	20
SKI/SIN3/HDAC complex/NCoR1	0.029	0.058	-10000	0	-0.47	4	4
MEF2C/TIF2	-0.012	0.13	0.32	1	-0.42	21	22
endothelial cell migration	0.16	0.16	0.61	4	-10000	0	4
MAX	0.038	0.015	-10000	0	-10000	0	0
RBBP7	0.028	0.005	-10000	0	-10000	0	0
RBBP4	0.027	0.022	-10000	0	-0.46	1	1
RUNX2	0.025	0.029	-10000	0	-0.42	2	2
RUNX3	0.022	0.048	-10000	0	-0.39	7	7
RUNX1	0.027	0.006	-10000	0	-10000	0	0
CTBP1	0.026	0.007	-10000	0	-10000	0	0
NR3C1	0.039	0.015	-10000	0	-10000	0	0
VDR	0.026	0.031	-10000	0	-0.46	2	2
CDKN1A	-0.012	0.1	-10000	0	-0.58	7	7
KAT2B	0.005	0.092	-10000	0	-0.46	19	19
SMAD2/SMAD2/SMAD4/FOXH1	-0.002	0.1	-10000	0	-0.3	17	17
DCP1A	0.024	0.009	-10000	0	-10000	0	0
SKI	0.027	0.006	-10000	0	-10000	0	0
SERPINE1	-0.16	0.17	-10000	0	-0.74	2	2
SMAD3/SMAD4/ATF2	0.034	0.061	-10000	0	-0.26	1	1
SMAD3/SMAD4/ATF3	0.031	0.073	-10000	0	-0.31	7	7
SAP30	0.026	0.019	-10000	0	-0.38	1	1
Cbp/p300/PIAS3	0.016	0.047	-10000	0	-0.28	1	1
JUN	-0.001	0.091	0.29	1	-10000	0	1
SMAD3/SMAD4/IRF7	0.026	0.082	-10000	0	-0.4	3	3
TFE3	-0.001	0.03	-10000	0	-10000	0	0
COL1A2	-0.094	0.16	-10000	0	-0.4	3	3
mesenchymal cell differentiation	-0.033	0.064	0.3	2	-10000	0	2
DLX1	-0.13	0.2	-10000	0	-0.39	196	196
TCF3	0.027	0.005	-10000	0	-10000	0	0
FOS	-0.031	0.16	-10000	0	-0.46	63	63
SMAD3/SMAD4/Max	0.061	0.065	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.047	0.021	-10000	0	-0.28	1	1
ZBTB17	0.03	0.013	-10000	0	-10000	0	0
LAMC1	0.001	0.044	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.033	0.06	-10000	0	-10000	0	0
IRF7	0.013	0.074	-10000	0	-0.4	15	15
ESR1	0.013	0.097	-10000	0	-0.42	24	24
HNF4A	-0.024	0.12	-10000	0	-0.39	49	49
MEF2C	0.007	0.12	0.43	2	-0.42	12	14
SMAD2-3/SMAD4	0.028	0.08	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.04	0.027	-10000	0	-0.28	1	1
IGHV3OR16-13	0.006	0.047	-10000	0	-0.34	9	9
TGIF2/HDAC complex	0.026	0.007	-10000	0	-10000	0	0
CREBBP	0.01	0.023	-10000	0	-10000	0	0
SKIL	0.02	0.013	-10000	0	-10000	0	0
HDAC1	0.028	0.005	-10000	0	-10000	0	0
HDAC2	0.028	0.005	-10000	0	-10000	0	0
SNIP1	0.029	0.004	-10000	0	-10000	0	0
GCN5L2	-0.005	0.008	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.018	0.06	-10000	0	-10000	0	0
MSG1/HSC70	0.036	0.037	-10000	0	-0.27	6	6
SMAD2	0.007	0.044	-10000	0	-10000	0	0
SMAD3	0.013	0.046	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.018	0.041	-10000	0	-0.32	2	2
SMAD2/SMAD2/SMAD4	-0.051	0.13	0.21	3	-0.4	49	52
NCOR1	0.027	0.006	-10000	0	-10000	0	0
NCOA2	-0.009	0.12	-10000	0	-0.46	36	36
NCOA1	0.028	0.003	-10000	0	-10000	0	0
MYOD/E2A	-0.022	0.13	-10000	0	-0.33	81	81
SMAD2-3/SMAD4/SP1/MIZ-1	0.011	0.12	-10000	0	-0.34	2	2
IFNB1	-0.003	0.077	-10000	0	-0.44	5	5
SMAD3/SMAD4/MEF2C	0.019	0.13	-10000	0	-0.42	11	11
CITED1	0.022	0.045	-10000	0	-0.39	6	6
SMAD2-3/SMAD4/ARC105	0.039	0.08	-10000	0	-10000	0	0
RBL1	0.025	0.023	-10000	0	-0.46	1	1
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.088	0.23	-10000	0	-0.53	106	106
RUNX1-3/PEBPB2	0.048	0.036	-10000	0	-0.22	7	7
SMAD7	-0.014	0.1	-10000	0	-0.42	1	1
MYC/MIZ-1	0.041	0.038	-10000	0	-10000	0	0
SMAD3/SMAD4	-0.063	0.11	0.28	4	-0.4	7	11
IL10	0.001	0.079	-10000	0	-0.36	9	9
PIASy/HDAC complex	0.031	0.013	-10000	0	-10000	0	0
PIAS3	0.024	0.007	-10000	0	-10000	0	0
CDK2	0.02	0.014	-10000	0	-10000	0	0
IL5	-0.003	0.069	-10000	0	-0.37	3	3
CDK4	0.01	0.023	-10000	0	-10000	0	0
PIAS4	0.031	0.013	-10000	0	-10000	0	0
ATF3	0.02	0.057	-10000	0	-0.43	8	8
SMAD3/SMAD4/SP1	-0.01	0.099	-10000	0	-0.31	1	1
FOXG1	-0.061	0.15	-10000	0	-0.41	79	79
FOXO3	-0.008	0.049	-10000	0	-10000	0	0
FOXO1	-0.008	0.049	-10000	0	-10000	0	0
FOXO4	-0.009	0.051	-10000	0	-0.33	1	1
heart looping	0.007	0.12	0.43	2	-0.42	12	14
CEBPB	0.012	0.032	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.069	0.14	-10000	0	-0.3	37	37
MYOD1	-0.069	0.17	-10000	0	-0.46	81	81
SMAD3/SMAD4/HNF4	0.006	0.098	-10000	0	-0.29	11	11
SMAD3/SMAD4/GATA3	0.028	0.085	-10000	0	-0.33	2	2
SnoN/SIN3/HDAC complex/NCoR1	0.02	0.013	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.057	0.068	-10000	0	-0.28	1	1
SMAD3/SMAD4/SP1-3	0.008	0.096	-10000	0	-10000	0	0
MED15	0.026	0.019	-10000	0	-0.39	1	1
SP1	-0.017	0.06	-10000	0	-10000	0	0
SIN3B	0.028	0.003	-10000	0	-10000	0	0
SIN3A	0.028	0.005	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.001	0.098	-10000	0	-0.3	13	13
ITGB5	-0.01	0.073	0.35	1	-10000	0	1
TGIF/SIN3/HDAC complex/CtBP	0.035	0.037	-10000	0	-0.32	1	1
SMAD3/SMAD4/AR	-0.052	0.15	-10000	0	-0.3	91	91
AR	-0.11	0.21	-10000	0	-0.46	139	139
negative regulation of cell growth	0.009	0.066	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	-0.02	0.13	-10000	0	-0.3	71	71
E2F5	0.022	0.038	-10000	0	-0.46	3	3
E2F4	0.027	0.006	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.012	0.094	-10000	0	-0.29	3	3
SMAD2-3/SMAD4/FOXO1-3a-4	-0.046	0.16	-10000	0	-0.36	101	101
TFDP1	0.027	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.022	0.1	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX2	0.034	0.064	-10000	0	-0.3	2	2
TGIF2	0.026	0.007	-10000	0	-10000	0	0
TGIF1	0.025	0.009	-10000	0	-10000	0	0
ATF2	0.026	0.022	-10000	0	-0.46	1	1

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.029	0.15	-10000	0	-0.46	57	57
GNB1/GNG2	0	0.12	-10000	0	-0.51	9	9
mol:DAG	-0.014	0.1	-10000	0	-0.52	7	7
PLCG1	-0.015	0.1	-10000	0	-0.54	7	7
YES1	-0.019	0.096	-10000	0	-0.49	10	10
FZD3	0.019	0.057	-10000	0	-0.46	7	7
FZD6	0.023	0.024	-10000	0	-0.46	1	1
G protein	0.003	0.12	0.27	3	-0.58	6	9
MAP3K7	-0.051	0.12	0.28	6	-0.43	17	23
mol:Ca2+	-0.014	0.098	-10000	0	-0.5	7	7
mol:IP3	-0.014	0.1	-10000	0	-0.52	7	7
NLK	0.006	0.066	-10000	0	-0.72	4	4
GNB1	0.027	0.006	-10000	0	-10000	0	0
CAMK2A	-0.052	0.14	0.29	7	-0.45	19	26
MAP3K7IP1	0	0	-10000	0	-10000	0	0
Noncanonical Wnts/FZD	-0.017	0.11	-10000	0	-0.5	12	12
CSNK1A1	0.027	0.006	-10000	0	-10000	0	0
GNAS	-0.021	0.098	-10000	0	-0.5	10	10
GO:0007205	-0.016	0.1	0.25	9	-0.47	9	18
WNT6	-0.009	0.12	-10000	0	-0.4	43	43
WNT4	0.013	0.079	-10000	0	-0.44	15	15
NFAT1/CK1 alpha	-0.014	0.14	0.28	5	-0.5	12	17
GNG2	0.026	0.007	-10000	0	-10000	0	0
WNT5A	0.019	0.052	-10000	0	-0.45	6	6
WNT11	-0.019	0.13	-10000	0	-0.41	52	52
CDC42	-0.008	0.1	-10000	0	-0.51	8	8

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.033	0.041	-10000	0	-0.29	7	7
PDGFRB	-0.042	0.15	-10000	0	-0.39	85	85
SPHK1	0.001	0.056	-10000	0	-0.64	3	3
mol:S1P	-0.003	0.054	-10000	0	-0.54	3	3
S1P1/S1P/Gi	-0.031	0.12	-10000	0	-0.4	33	33
GNAO1	0.022	0.04	-10000	0	-0.41	4	4
PDGFB-D/PDGFRB/PLCgamma1	-0.032	0.13	0.27	1	-0.37	24	25
PLCG1	-0.034	0.11	-10000	0	-0.37	32	32
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.042	0.15	-10000	0	-0.39	85	85
GNAI2	0.023	0.011	-10000	0	-10000	0	0
GNAI3	0.026	0.008	-10000	0	-10000	0	0
GNAI1	0.025	0.023	-10000	0	-0.47	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	0	0.031	-10000	0	-0.25	7	7
S1P1/S1P	-0.005	0.056	-10000	0	-0.33	3	3
negative regulation of cAMP metabolic process	-0.03	0.12	-10000	0	-0.39	33	33
MAPK3	-0.04	0.14	-10000	0	-0.44	33	33
calcium-dependent phospholipase C activity	-0.001	0.002	-10000	0	-10000	0	0
Rac1/GDP	0.019	0.005	-10000	0	-10000	0	0
RhoA/GDP	0.018	0.007	-10000	0	-10000	0	0
KDR	0.025	0.031	-10000	0	-0.46	2	2
PLCB2	0	0.063	0.24	2	-0.29	5	7
RAC1	0.026	0.007	-10000	0	-10000	0	0
RhoA/GTP	-0.004	0.048	-10000	0	-0.28	3	3
receptor internalization	-0.005	0.052	-10000	0	-0.31	3	3
PTGS2	-0.043	0.18	-10000	0	-0.66	19	19
Rac1/GTP	-0.004	0.047	-10000	0	-0.29	3	3
RHOA	0.025	0.009	-10000	0	-10000	0	0
VEGFA	0.021	0.045	-10000	0	-0.39	6	6
negative regulation of T cell proliferation	-0.03	0.12	-10000	0	-0.39	33	33
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	0.011	0.08	-10000	0	-0.42	17	17
MAPK1	-0.039	0.14	-10000	0	-0.44	33	33
S1P1/S1P/PDGFB-D/PDGFRB	-0.011	0.087	0.23	2	-0.3	3	5
ABCC1	0.025	0.032	-10000	0	-0.39	3	3

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.025	0.032	-10000	0	-0.39	3	3
ANTXR2	0.018	0.06	-10000	0	-0.39	11	11
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.002	0.007	-10000	0	-0.047	13	13
monocyte activation	-0.016	0.1	-10000	0	-0.37	36	36
MAP2K2	0.001	0.094	-10000	0	-0.56	14	14
MAP2K1	-0.003	0.007	-10000	0	-10000	0	0
MAP2K7	-0.003	0.007	-10000	0	-10000	0	0
MAP2K6	-0.014	0.05	-10000	0	-0.24	24	24
CYAA	-0.008	0.029	-10000	0	-0.19	13	13
MAP2K4	-0.003	0.007	-10000	0	-10000	0	0
IL1B	-0.017	0.063	0.19	7	-0.19	52	59
Channel	0.029	0.038	-10000	0	-0.2	13	13
NLRP1	-0.003	0.011	-10000	0	-0.19	1	1
CALM1	0.026	0.007	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.003	0.075	-10000	0	-0.38	19	19
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.002	0.007	0.047	13	-10000	0	13
MAPK3	-0.003	0.007	-10000	0	-10000	0	0
MAPK1	-0.003	0.009	0.15	1	-10000	0	1
PGR	-0.028	0.073	0.15	1	-0.23	57	58
PA/Cellular Receptors	0.03	0.042	-10000	0	-0.23	13	13
apoptosis	-0.002	0.007	-10000	0	-0.047	13	13
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.028	0.034	-10000	0	-0.18	13	13
macrophage activation	-0.004	0.009	0.14	1	-10000	0	1
TNF	0.008	0.088	-10000	0	-0.4	23	23
VCAM1	-0.015	0.1	-10000	0	-0.37	34	34
platelet activation	-0.003	0.075	-10000	0	-0.38	19	19
MAPKKK cascade	0.003	0.021	0.11	1	-0.1	2	3
IL18	-0.005	0.038	0.18	2	-0.24	11	13
negative regulation of macrophage activation	-0.002	0.007	-10000	0	-0.047	13	13
LEF	-0.002	0.007	-10000	0	-0.047	13	13
CASP1	0	0.009	-10000	0	-0.088	2	2
mol:cAMP	-0.003	0.075	-10000	0	-0.38	19	19
necrosis	-0.002	0.007	-10000	0	-0.047	13	13
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.028	0.036	-10000	0	-0.19	13	13
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

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

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
MET/RANBP9	0.035	0.035	-10000	0	-0.29	5	5
CRKL	0.015	0.12	0.3	8	-0.46	21	29
mol:PIP3	0	0.035	-10000	0	-0.74	1	1
AKT1	0.004	0.051	-10000	0	-0.65	1	1
PTK2B	0.026	0.008	-10000	0	-10000	0	0
RAPGEF1	0.019	0.12	0.28	14	-0.44	20	34
RANBP10	0.027	0.006	-10000	0	-10000	0	0
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
HGF/MET/SHIP2	0.031	0.068	-10000	0	-0.26	24	24
MAP3K5	0.014	0.12	0.28	7	-0.48	19	26
HGF/MET/CIN85/CBL/ENDOPHILINS	0.044	0.072	-10000	0	-0.25	17	17
AP1	-0.01	0.11	-10000	0	-0.3	63	63
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.028	0.004	-10000	0	-10000	0	0
apoptosis	-0.086	0.28	-10000	0	-0.73	80	80
STAT3 (dimer)	0.018	0.068	-10000	0	-0.31	7	7
GAB1/CRKL/SHP2/PI3K	0.031	0.1	0.32	2	-0.45	9	11
INPP5D	0.025	0.031	-10000	0	-0.46	2	2
CBL/CRK	0.022	0.11	0.31	1	-0.44	20	21
PTPN11	0.028	0.002	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.027	0.006	-10000	0	-10000	0	0
PTEN	0.027	0.006	-10000	0	-10000	0	0
ELK1	-0.005	0.071	0.28	22	-0.21	1	23
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	0.012	0.052	0.15	1	-0.25	8	9
PAK1	0.011	0.068	0.4	5	-0.62	1	6
HGF/MET/RANBP10	0.034	0.072	-10000	0	-0.26	27	27
HRAS	0	0.12	-10000	0	-0.52	17	17
DOCK1	0.014	0.12	0.28	8	-0.45	19	27
GAB1	0.008	0.12	0.25	1	-0.47	22	23
CRK	0.01	0.11	0.28	2	-0.46	21	23
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	0.001	0.12	-10000	0	-0.47	25	25
JUN	0.028	0.004	-10000	0	-10000	0	0
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	0.002	0.044	-10000	0	-0.2	18	18
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
cell morphogenesis	0.07	0.13	0.32	51	-0.41	6	57
GRB2/SHC	0.033	0.057	-10000	0	-0.23	6	6
FOS	-0.034	0.16	-10000	0	-0.46	63	63
GLMN	0.004	0.001	-10000	0	-10000	0	0
cell motility	-0.005	0.07	0.28	22	-0.21	1	23
HGF/MET/MUC20	0.019	0.067	-10000	0	-0.26	28	28
cell migration	0.031	0.054	-10000	0	-0.22	6	6
GRB2	0.027	0.004	-10000	0	-10000	0	0
CBL	0.025	0.008	-10000	0	-10000	0	0
MET/RANBP10	0.034	0.037	-10000	0	-0.29	6	6
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.013	0.052	-10000	0	-0.33	4	4
MET/MUC20	0.016	0.034	-10000	0	-0.29	6	6
RAP1B	0.025	0.12	0.3	14	-0.44	16	30
RAP1A	0.017	0.11	0.28	11	-0.43	18	29
HGF/MET/RANBP9	0.035	0.071	-10000	0	-0.26	25	25
RAF1	0.006	0.12	-10000	0	-0.5	14	14
STAT3	0.018	0.068	-10000	0	-0.31	7	7
cell proliferation	0.02	0.1	0.31	9	-0.36	16	25
RPS6KB1	0.011	0.023	-10000	0	-0.26	1	1
MAPK3	-0.008	0.098	0.68	7	-10000	0	7
MAPK1	-0.011	0.084	0.72	4	-10000	0	4
RANBP9	0.027	0.006	-10000	0	-10000	0	0
MAPK8	0.028	0.12	0.3	6	-0.45	17	23
SRC	0.007	0.047	-10000	0	-0.31	4	4
PI3K	0.023	0.051	-10000	0	-0.25	6	6
MET/Glomulin	0.016	0.037	-10000	0	-0.26	6	6
SOS1	0.028	0.004	-10000	0	-10000	0	0
MAP2K1	0.007	0.11	0.3	1	-0.47	13	14
MET	0.022	0.048	-10000	0	-0.41	6	6
MAP4K1	0.012	0.13	0.31	5	-0.51	19	24
PTK2	0.023	0.011	-10000	0	-10000	0	0
MAP2K2	0.007	0.11	-10000	0	-0.48	12	12
BAD	0.008	0.06	0.38	3	-0.62	1	4
MAP2K4	0.015	0.12	0.27	9	-0.43	19	28
SHP2/GRB2/SOS1/GAB1	0.03	0.1	-10000	0	-0.42	17	17
INPPL1	0.024	0.01	-10000	0	-10000	0	0
PXN	0.028	0.002	-10000	0	-10000	0	0
SH3KBP1	0.026	0.026	-10000	0	-0.39	2	2
HGS	0	0.042	-10000	0	-0.23	6	6
PLCgamma1/PKC	0.02	0.005	-10000	0	-10000	0	0
HGF	0.006	0.095	-10000	0	-0.44	22	22
RASA1	0.024	0.031	-10000	0	-0.46	2	2
NCK1	0.023	0.011	-10000	0	-10000	0	0
PTPRJ	0.027	0.005	-10000	0	-10000	0	0
NCK/PLCgamma1	0.03	0.05	-10000	0	-0.24	4	4
PDPK1	-0.002	0.036	-10000	0	-0.68	1	1
HGF/MET/SHIP	0.033	0.077	-10000	0	-0.27	29	29

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.019	0.088	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0.001	-10000	0	-10000	0	0
CRKL	0.026	0.019	-10000	0	-0.39	1	1
STAT1 (dimer)/Cbp/p300	0.023	0.096	0.29	1	-10000	0	1
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.032	0.044	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.032	0.07	-10000	0	-0.26	5	5
CaM/Ca2+	0.02	0.084	-10000	0	-10000	0	0
RAP1A	0.027	0.005	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	0.004	0.093	-10000	0	-0.33	10	10
AKT1	0.041	0.11	0.3	20	-10000	0	20
MAP2K1	-0.005	0.077	0.24	3	-10000	0	3
MAP3K11	-0.002	0.079	0.28	1	-10000	0	1
IFNGR1	0.02	0.023	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.13	0.21	-10000	0	-0.44	126	126
Rap1/GTP	-0.007	0.058	-10000	0	-10000	0	0
CRKL/C3G	0.038	0.018	-10000	0	-0.27	1	1
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.021	0.097	-10000	0	-10000	0	0
CEBPB	0.023	0.11	0.31	4	-0.48	7	11
STAT3	0.028	0.003	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.004	0.14	-10000	0	-0.7	8	8
STAT1	-0.008	0.09	0.28	1	-0.33	10	11
CALM1	0.026	0.007	-10000	0	-10000	0	0
IFN-gamma (dimer)	-0.05	0.16	-10000	0	-0.38	97	97
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
STAT1 (dimer)/PIAS1	0.007	0.093	0.28	1	-0.32	10	11
CEBPB/PTGES2/Cbp/p300	0.017	0.068	-10000	0	-0.34	4	4
mol:Ca2+	0.017	0.085	-10000	0	-10000	0	0
MAPK3	0.004	0.12	-10000	0	-0.65	10	10
STAT1 (dimer)	-0.037	0.097	-10000	0	-0.36	5	5
MAPK1	0.007	0.1	-10000	0	-0.58	7	7
JAK2	0.017	0.023	-10000	0	-10000	0	0
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
JAK1	0.02	0.023	-10000	0	-10000	0	0
CAMK2D	0.027	0.005	-10000	0	-10000	0	0
DAPK1	0.024	0.095	0.27	9	-0.47	7	16
SMAD7	0.004	0.064	0.17	21	-10000	0	21
CBL/CRKL/C3G	0.019	0.084	0.28	2	-10000	0	2
PI3K	0.011	0.075	-10000	0	-10000	0	0
IFNG	-0.05	0.16	-10000	0	-0.38	97	97
apoptosis	0.021	0.083	0.25	6	-0.42	6	12
CAMK2G	0.028	0.004	-10000	0	-10000	0	0
STAT3 (dimer)	0.028	0.003	-10000	0	-10000	0	0
CAMK2A	-0.082	0.2	-10000	0	-0.46	114	114
CAMK2B	-0.11	0.22	-10000	0	-0.46	143	143
FRAP1	0.03	0.1	0.29	20	-10000	0	20
PRKCD	0.036	0.11	0.3	16	-10000	0	16
RAP1B	0.027	0.006	-10000	0	-10000	0	0
negative regulation of cell growth	-0.032	0.07	-10000	0	-0.26	5	5
PTPN2	0.026	0.007	-10000	0	-10000	0	0
EP300	0.027	0.022	-10000	0	-0.46	1	1
IRF1	-0.005	0.087	0.28	8	-10000	0	8
STAT1 (dimer)/PIASy	0.007	0.093	0.25	3	-0.32	10	13
SOCS1	-0.007	0.15	-10000	0	-1	8	8
mol:GDP	0.016	0.08	0.26	2	-10000	0	2
CASP1	0.004	0.065	0.18	21	-0.3	1	22
PTGES2	0.027	0.005	-10000	0	-10000	0	0
IRF9	0.026	0.046	0.17	12	-10000	0	12
mol:PI-3-4-5-P3	0.003	0.067	-10000	0	-10000	0	0
RAP1/GDP	0.01	0.069	-10000	0	-10000	0	0
CBL	0.001	0.078	0.27	2	-10000	0	2
MAP3K1	0	0.08	0.28	2	-10000	0	2
PIAS1	0.027	0.004	-10000	0	-10000	0	0
PIAS4	0.027	0.005	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.032	0.07	-10000	0	-0.26	5	5
PTPN11	0.002	0.086	0.29	2	-10000	0	2
CREBBP	0.028	0.004	-10000	0	-10000	0	0
RAPGEF1	0.027	0.005	-10000	0	-10000	0	0

×

FAS signaling pathway (CD95)

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
SPTAN1	0	0.038	0.21	10	-10000	0	10
RFC1	-0.002	0.028	0.21	3	-10000	0	3
PRKDC	0.016	0.069	0.22	46	-10000	0	46
RIPK1	0.027	0.007	-10000	0	-10000	0	0
CASP7	0.012	0.084	-10000	0	-0.55	9	9
FASLG/FAS/FADD/FAF1	0	0.059	0.22	7	-0.25	13	20
MAP2K4	0.026	0.12	0.3	7	-0.44	11	18
mol:ceramide	0.009	0.086	-10000	0	-0.33	12	12
GSN	0.001	0.037	0.21	10	-10000	0	10
FASLG/FAS/FADD/FAF1/Caspase 8	0.017	0.081	0.25	2	-0.32	9	11
FAS	0.023	0.026	-10000	0	-0.46	1	1
BID	-0.015	0.024	0.26	1	-0.24	2	3
MAP3K1	0.042	0.098	0.32	6	-0.41	6	12
MAP3K7	0.027	0.006	-10000	0	-10000	0	0
RB1	-0.003	0.026	0.2	1	-10000	0	1
CFLAR	0.028	0.006	-10000	0	-10000	0	0
HGF/MET	0.028	0.084	-10000	0	-0.27	34	34
ARHGDIB	0.003	0.044	0.22	15	-10000	0	15
FADD	0.017	0.017	-10000	0	-10000	0	0
actin filament polymerization	0.003	0.046	-10000	0	-0.21	10	10
NFKB1	0.005	0.1	-10000	0	-0.54	10	10
MAPK8	0.01	0.16	0.29	7	-0.46	37	44
DFFA	-0.003	0.024	0.2	1	-10000	0	1
DNA fragmentation during apoptosis	-0.006	0.041	0.21	4	-0.31	2	6
FAS/FADD/MET	0.031	0.042	-10000	0	-0.26	5	5
CFLAR/RIP1	0.039	0.013	-10000	0	-10000	0	0
FAIM3	0.021	0.056	-10000	0	-0.4	9	9
FAF1	0.023	0.017	-10000	0	-10000	0	0
PARP1	-0.003	0.03	0.21	3	-10000	0	3
DFFB	-0.003	0.035	0.21	4	-0.31	2	6
CHUK	0.003	0.092	-10000	0	-0.54	8	8
FASLG	-0.01	0.12	-10000	0	-0.42	39	39
FAS/FADD	0.024	0.029	-10000	0	-0.33	1	1
HGF	0.006	0.095	-10000	0	-0.44	22	22
LMNA	-0.005	0.033	0.18	3	-10000	0	3
CASP6	-0.003	0.024	0.18	2	-10000	0	2
CASP10	0.024	0.015	-10000	0	-10000	0	0
CASP3	0	0.023	0.23	2	-0.18	1	3
PTPN13	0.018	0.064	-10000	0	-0.46	9	9
CASP8	-0.016	0.029	0.19	9	-10000	0	9
IL6	-0.07	0.36	-10000	0	-1.2	47	47
MET	0.022	0.048	-10000	0	-0.41	6	6
ICAD/CAD	-0.003	0.03	0.19	3	-0.29	2	5
FASLG/FAS/FADD/FAF1/Caspase 10	0.009	0.086	-10000	0	-0.33	12	12
activation of caspase activity by cytochrome c	-0.015	0.024	0.26	1	-0.24	2	3
PAK2	0.04	0.093	0.22	100	-10000	0	100
BCL2	0.022	0.039	-10000	0	-0.41	4	4

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.016	0.16	-10000	0	-10000	0	0
CRP	-0.034	0.16	0.49	2	-0.66	1	3
cell cycle arrest	-0.035	0.16	-10000	0	-0.61	1	1
TIMP1	-0.016	0.16	-10000	0	-0.58	4	4
IL6ST	-0.03	0.16	-10000	0	-0.46	60	60
Rac1/GDP	-0.024	0.12	-10000	0	-0.46	15	15
AP1	0.007	0.14	-10000	0	-0.55	8	8
GAB2	0.022	0.038	-10000	0	-0.46	3	3
TNFSF11	-0.057	0.18	-10000	0	-0.62	1	1
HSP90B1	0.023	0.092	-10000	0	-0.69	5	5
GAB1	0.027	0.006	-10000	0	-10000	0	0
MAPK14	-0.029	0.12	-10000	0	-0.45	17	17
AKT1	0.047	0.064	0.3	8	-0.58	1	9
FOXO1	0.046	0.06	0.33	4	-0.55	1	5
MAP2K6	-0.036	0.12	-10000	0	-0.46	19	19
mol:GTP	0	0.001	-10000	0	-10000	0	0
MAP2K4	-0.025	0.12	-10000	0	-0.46	13	13
MITF	-0.033	0.12	-10000	0	-0.43	22	22
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.027	0.019	-10000	0	-0.39	1	1
A2M	0.018	0.1	-10000	0	-1.1	4	4
CEBPB	0.028	0.014	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.005	0.11	-10000	0	-0.5	13	13
STAT3	-0.04	0.16	-10000	0	-0.64	1	1
STAT1	0.005	0.085	-10000	0	-0.78	5	5
CEBPD	-0.012	0.16	-10000	0	-10000	0	0
PIK3CA	0.021	0.013	-10000	0	-10000	0	0
PI3K	0.028	0.03	-10000	0	-0.33	2	2
JUN	0.027	0.004	-10000	0	-10000	0	0
PIAS3/MITF	-0.022	0.12	-10000	0	-0.42	20	20
MAPK11	-0.029	0.12	-10000	0	-0.47	17	17
STAT3 (dimer)/FOXO1	0.009	0.15	0.39	2	-10000	0	2
GRB2/SOS1/GAB family	0.017	0.12	-10000	0	-0.43	11	11
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.021	0.12	-10000	0	-0.45	16	16
GRB2	0.028	0.004	-10000	0	-10000	0	0
JAK2	0.024	0.01	-10000	0	-10000	0	0
LBP	-0.11	0.33	-10000	0	-0.88	70	70
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
JAK1	0.029	0.006	-10000	0	-10000	0	0
MYC	0.004	0.16	0.49	2	-10000	0	2
FGG	-0.045	0.17	-10000	0	-0.62	1	1
macrophage differentiation	-0.035	0.16	-10000	0	-0.61	1	1
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0.008	0.13	-10000	0	-0.39	17	17
JUNB	-0.027	0.14	-10000	0	-10000	0	0
FOS	-0.034	0.16	-10000	0	-0.46	63	63
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.026	0.12	-10000	0	-0.42	21	21
STAT1/PIAS1	-0.016	0.12	-10000	0	-0.43	12	12
GRB2/SOS1/GAB family/SHP2/PI3K	0.044	0.056	-10000	0	-0.48	2	2
STAT3 (dimer)	-0.038	0.16	-10000	0	-0.63	1	1
PRKCD	-0.016	0.14	0.35	8	-0.52	4	12
IL6R	0.022	0.057	-10000	0	-0.46	7	7
SOCS3	-0.025	0.13	-10000	0	-0.6	7	7
gp130 (dimer)/JAK1/JAK1/LMO4	0.017	0.11	-10000	0	-0.28	59	59
Rac1/GTP	-0.025	0.13	-10000	0	-0.46	15	15
HCK	0.024	0.029	-10000	0	-0.42	2	2
MAPKKK cascade	0.022	0.11	-10000	0	-0.53	10	10
bone resorption	-0.053	0.17	-10000	0	-0.59	1	1
IRF1	-0.028	0.15	-10000	0	-10000	0	0
mol:GDP	-0.033	0.12	-10000	0	-0.41	23	23
SOS1	0.028	0.004	-10000	0	-10000	0	0
VAV1	-0.033	0.12	-10000	0	-0.42	23	23
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.021	0.13	-10000	0	-0.49	20	20
PTPN11	0.016	0.049	-10000	0	-0.7	2	2
IL6/IL6RA	0.004	0.11	-10000	0	-0.32	51	51
gp130 (dimer)/TYK2/TYK2/LMO4	0.014	0.11	-10000	0	-0.28	60	60
gp130 (dimer)/JAK2/JAK2/LMO4	0.012	0.1	-10000	0	-0.28	55	55
IL6	-0.016	0.14	-10000	0	-0.45	46	46
PIAS3	0.027	0.006	-10000	0	-10000	0	0
PTPRE	0.024	0.011	-10000	0	-10000	0	0
PIAS1	0.027	0.004	-10000	0	-10000	0	0
RAC1	0.026	0.007	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.028	0.12	-10000	0	-0.33	43	43
LMO4	0.028	0.01	-10000	0	-10000	0	0
STAT3 (dimer)/PIAS3	-0.03	0.17	-10000	0	-0.64	1	1
MCL1	0.05	0.073	0.54	2	-0.52	1	3

×

Signaling events mediated by PRL

Figure S75. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S75. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.025	0.032	-10000	0	-0.39	3	3
mol:Halofuginone	0.004	0	-10000	0	-10000	0	0
ITGA1	-0.031	0.14	-10000	0	-0.39	71	71
CDKN1A	0.012	0.05	-10000	0	-0.3	10	10
PRL-3/alpha Tubulin	0.031	0.034	-10000	0	-0.27	5	5
mol:Ca2+	-0.062	0.12	0.17	3	-0.34	76	79
AGT	-0.066	0.19	-10000	0	-0.46	98	98
CCNA2	-0.007	0.046	-10000	0	-0.41	1	1
TUBA1B	0.028	0.003	-10000	0	-10000	0	0
EGR1	0.002	0.068	-10000	0	-0.32	22	22
CDK2/Cyclin E1	0.04	0.081	0.28	1	-0.37	4	5
MAPK3	0.009	0.029	-10000	0	-0.27	5	5
PRL-2 /Rab GGTase beta	0.04	0.007	-10000	0	-10000	0	0
MAPK1	0.009	0.029	-10000	0	-0.27	5	5
PTP4A1	-0.004	0.048	-10000	0	-10000	0	0
PTP4A3	0.019	0.042	-10000	0	-0.39	5	5
PTP4A2	0.027	0.004	-10000	0	-10000	0	0
ITGB1	0.009	0.029	-10000	0	-0.27	5	5
SRC	0.026	0.007	-10000	0	-10000	0	0
RAC1	0.012	0.03	-10000	0	-0.3	2	2
Rab GGTase beta/Rab GGTase alpha	0.038	0.011	-10000	0	-10000	0	0
PRL-1/ATF-5	0.02	0.072	-10000	0	-10000	0	0
RABGGTA	0.026	0.007	-10000	0	-10000	0	0
BCAR1	-0.013	0.02	0.17	5	-10000	0	5
RHOC	0.011	0.039	-10000	0	-0.3	5	5
RHOA	-0.002	0.072	-10000	0	-0.3	25	25
cell motility	0.019	0.074	0.31	2	-0.31	3	5
PRL-1/alpha Tubulin	0.023	0.067	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	-0.01	0.1	-10000	0	-0.27	69	69
ROCK1	0.024	0.063	0.35	1	-0.3	2	3
RABGGTB	0.027	0.004	-10000	0	-10000	0	0
CDK2	0.028	0.003	-10000	0	-10000	0	0
mitosis	-0.004	0.048	-10000	0	-10000	0	0
ATF5	0.019	0.057	-10000	0	-0.39	10	10

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.02	0.015	-10000	0	-10000	0	0
TRAF2/ASK1	0.033	0.027	-10000	0	-0.22	5	5
ATM	0.025	0.008	-10000	0	-10000	0	0
MAP2K3	-0.021	0.11	0.42	2	-0.35	28	30
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	-0.019	0.11	0.31	3	-0.35	24	27
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.021	0.053	-10000	0	-0.43	7	7
TXN	0.008	0.001	-10000	0	-10000	0	0
CALM1	0.026	0.007	-10000	0	-10000	0	0
GADD45A	0.027	0.019	-10000	0	-0.39	1	1
GADD45B	0.027	0.005	-10000	0	-10000	0	0
MAP3K1	0.026	0.007	-10000	0	-10000	0	0
MAP3K6	0.026	0.022	-10000	0	-0.46	1	1
MAP3K7	0.027	0.005	-10000	0	-10000	0	0
MAP3K4	0.027	0.005	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.038	0.019	-10000	0	-0.33	1	1
TAK1/TAB family	-0.005	0.017	-10000	0	-0.13	7	7
RAC1/OSM/MEKK3	0.047	0.03	-10000	0	-0.21	5	5
TRAF2	0.023	0.041	-10000	0	-0.39	5	5
RAC1/OSM/MEKK3/MKK3	-0.007	0.092	-10000	0	-0.32	14	14
TRAF6	0.008	0.002	-10000	0	-10000	0	0
RAC1	0.026	0.007	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.11	0.22	-10000	0	-0.46	143	143
CCM2	0.022	0.045	-10000	0	-0.39	6	6
CaM/Ca2+/CAMKIIB	-0.051	0.14	-10000	0	-0.28	138	138
MAPK11	0.027	0.005	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.034	0.13	-10000	0	-0.25	137	137
OSM/MEKK3	0.036	0.032	-10000	0	-0.27	5	5
TAOK1	0.006	0.052	-10000	0	-0.33	12	12
TAOK2	0.014	0.005	-10000	0	-10000	0	0
TAOK3	0.014	0.005	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.027	0.006	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.027	0.005	-10000	0	-10000	0	0
MAP3K10	0.027	0.005	-10000	0	-10000	0	0
MAP3K3	0.028	0.003	-10000	0	-10000	0	0
TRX/ASK1	0.025	0.01	-10000	0	-10000	0	0
GADD45/MTK1/MTK1	0.056	0.039	-10000	0	-0.24	4	4

×

BARD1 signaling events

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
BARD1/CSTF1	0.017	0.086	-10000	0	-0.33	29	29
ATM	0.025	0.008	-10000	0	-10000	0	0
UBE2D3	0.027	0.005	-10000	0	-10000	0	0
PRKDC	0.025	0.009	-10000	0	-10000	0	0
ATR	0.023	0.011	-10000	0	-10000	0	0
UBE2L3	0.027	0.006	-10000	0	-10000	0	0
FANCD2	0.016	0.011	-10000	0	-10000	0	0
protein ubiquitination	0.045	0.077	-10000	0	-0.25	26	26
XRCC5	0.027	0.006	-10000	0	-10000	0	0
XRCC6	0.027	0.004	-10000	0	-10000	0	0
M/R/N Complex	0.044	0.024	-10000	0	-10000	0	0
MRE11A	0.025	0.008	-10000	0	-10000	0	0
DNA-PK	0.048	0.021	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.012	0.097	-10000	0	-0.51	10	10
FANCF	0.023	0.043	-10000	0	-0.46	4	4
BRCA1	0.028	0.003	-10000	0	-10000	0	0
CCNE1	0.025	0.032	-10000	0	-0.39	3	3
CDK2/Cyclin E1	0.038	0.025	-10000	0	-0.27	3	3
FANCG	0.024	0.01	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.018	0.088	-10000	0	-0.33	30	30
FANCE	0.027	0.006	-10000	0	-10000	0	0
FANCC	0.027	0.005	-10000	0	-10000	0	0
NBN	0.025	0.009	-10000	0	-10000	0	0
FANCA	0.025	0.026	-10000	0	-0.39	2	2
DNA repair	0.012	0.085	0.28	6	-0.38	4	10
BRCA1/BARD1/ubiquitin	0.018	0.088	-10000	0	-0.33	30	30
BARD1/DNA-PK	0.046	0.069	-10000	0	-0.26	21	21
FANCL	0.027	0.019	-10000	0	-0.39	1	1
mRNA polyadenylation	-0.017	0.086	0.33	29	-10000	0	29
BRCA1/BARD1/CTIP/M/R/N Complex	0.01	0.073	-10000	0	-0.28	5	5
BRCA1/BACH1/BARD1/TopBP1	0.029	0.074	-10000	0	-0.28	25	25
BRCA1/BARD1/P53	0.036	0.076	-10000	0	-0.26	27	27
BARD1/CSTF1/BRCA1	0.032	0.079	-10000	0	-0.28	29	29
BRCA1/BACH1	0.028	0.003	-10000	0	-10000	0	0
BARD1	-0.002	0.12	-10000	0	-0.46	30	30
PCNA	0.026	0.007	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	0.033	0.08	-10000	0	-0.28	30	30
BRCA1/BARD1/UbcH7	0.032	0.079	-10000	0	-0.28	29	29
BRCA1/BARD1/RAD51/PCNA	0.044	0.079	-10000	0	-0.26	29	29
BARD1/DNA-PK/P53	0.052	0.073	-10000	0	-0.24	22	22
BRCA1/BARD1/Ubiquitin	0.018	0.088	-10000	0	-0.33	30	30
BRCA1/BARD1/CTIP	0.022	0.071	-10000	0	-0.26	29	29
FA complex	0.036	0.039	-10000	0	-10000	0	0
BARD1/EWS	0.018	0.086	-10000	0	-0.33	29	29
RBBP8	0.013	0.005	-10000	0	-10000	0	0
TP53	0.023	0.043	-10000	0	-0.46	4	4
TOPBP1	0.024	0.01	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.034	0.075	0.25	27	-10000	0	27
BRCA1/BARD1	0.051	0.08	-10000	0	-0.25	26	26
CSTF1	0.027	0.006	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.001	0.082	-10000	0	-0.33	30	30
CDK2	0.028	0.003	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.026	0.026	-10000	0	-0.39	2	2
RAD50	0.026	0.007	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.018	0.088	-10000	0	-0.33	30	30
EWSR1	0.027	0.005	-10000	0	-10000	0	0

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.028	0.003	-10000	0	-10000	0	0
mol:PIP3	0.001	0.03	-10000	0	-0.21	3	3
FRAP1	0.029	0.068	-10000	0	-0.42	7	7
AKT1	0.034	0.074	0.18	11	-0.24	1	12
INSR	0.027	0.022	-10000	0	-0.46	1	1
Insulin Receptor/Insulin	0.028	0.022	-10000	0	-0.25	3	3
mol:GTP	0.06	0.071	0.28	5	-10000	0	5
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0.01	0.021	-10000	0	-10000	0	0
TSC2	0.027	0.004	-10000	0	-10000	0	0
RHEB/GDP	0.014	0.03	-10000	0	-10000	0	0
TSC1	0.027	0.005	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.017	0.051	-10000	0	-0.2	25	25
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.02	0.03	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.028	0.004	-10000	0	-10000	0	0
RPS6KB1	0.048	0.071	0.23	13	-0.26	1	14
MAP3K5	0.005	0.034	0.19	7	-0.18	10	17
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
apoptosis	0.005	0.034	0.19	7	-0.18	10	17
mol:LY294002	0	0	-10000	0	-0.001	23	23
EIF4B	0.045	0.068	0.23	14	-10000	0	14
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.057	0.061	0.22	8	-10000	0	8
eIF4E/eIF4G1/eIF4A1	0.012	0.033	-10000	0	-0.27	5	5
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.023	0.042	-10000	0	-0.22	5	5
mTOR/RHEB/GTP/Raptor/GBL	0.037	0.06	0.21	20	-0.19	1	21
FKBP1A	0.027	0.007	-10000	0	-10000	0	0
RHEB/GTP	0.053	0.058	-10000	0	-10000	0	0
mol:Amino Acids	0	0	-10000	0	-0.001	23	23
FKBP12/Rapamycin	0.021	0.006	-10000	0	-10000	0	0
PDPK1	0.023	0.072	0.17	10	-0.22	1	11
EIF4E	0.027	0.005	-10000	0	-10000	0	0
ASK1/PP5C	0.038	0.1	-10000	0	-0.48	16	16
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	-0.005	0.099	-10000	0	-0.83	5	5
TSC1/TSC2	0.066	0.077	0.3	6	-10000	0	6
tumor necrosis factor receptor activity	0	0	0.001	23	-10000	0	23
RPS6	0.025	0.009	-10000	0	-10000	0	0
PPP5C	0.027	0.005	-10000	0	-10000	0	0
EIF4G1	0.02	0.013	-10000	0	-10000	0	0
IRS1	0	0.05	-10000	0	-0.22	25	25
INS	-0.017	0.025	-10000	0	-0.39	2	2
PTEN	0.026	0.006	-10000	0	-10000	0	0
PDK2	0.024	0.072	0.16	105	-0.21	2	107
EIF4EBP1	-0.027	0.22	-10000	0	-1	24	24
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
PPP2R5D	0.03	0.068	0.25	6	-0.37	7	13
peptide biosynthetic process	-0.009	0.024	0.18	4	-0.22	3	7
RHEB	0.027	0.007	-10000	0	-10000	0	0
EIF4A1	0.027	0.006	-10000	0	-10000	0	0
mol:Rapamycin	0.001	0.001	0.003	133	-10000	0	133
EEF2	-0.009	0.025	0.18	4	-0.22	3	7
eIF4E/4E-BP1	-0.012	0.21	-10000	0	-0.95	24	24

×

Nectin adhesion pathway

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
PDGFRB	-0.042	0.15	-10000	0	-0.39	85	85
alphaV beta3 Integrin	0.024	0.07	-10000	0	-0.29	23	23
PTK2	0.008	0.087	-10000	0	-0.44	8	8
positive regulation of JNK cascade	0.01	0.092	-10000	0	-0.32	19	19
CDC42/GDP	0.043	0.12	0.3	4	-0.4	18	22
Rac1/GDP	0.039	0.12	0.3	2	-0.4	16	18
RAP1B	0.027	0.006	-10000	0	-10000	0	0
RAP1A	0.027	0.005	-10000	0	-10000	0	0
CTNNB1	0.024	0.009	-10000	0	-10000	0	0
CDC42/GTP	0.026	0.12	-10000	0	-0.4	19	19
nectin-3/I-afadin	0.023	0.066	-10000	0	-0.31	18	18
RAPGEF1	0.028	0.11	0.31	6	-0.43	11	17
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.01	0.11	-10000	0	-0.47	13	13
PDGFB-D/PDGFRB	-0.042	0.15	-10000	0	-0.39	85	85
TLN1	0.001	0.034	0.17	2	-0.33	2	4
Rap1/GTP	0.014	0.074	-10000	0	-0.33	9	9
IQGAP1	0.027	0.004	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.049	0.017	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.023	0.066	-10000	0	-0.31	18	18
PVR	0.027	0.005	-10000	0	-10000	0	0
Necl-5(dimer)	0.027	0.005	-10000	0	-10000	0	0
mol:GDP	0.031	0.14	0.35	3	-0.48	18	21
MLLT4	0.027	0.005	-10000	0	-10000	0	0
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
PI3K	0.009	0.1	-10000	0	-0.28	11	11
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.035	0.031	-10000	0	-0.33	3	3
positive regulation of lamellipodium assembly	0.017	0.082	-10000	0	-0.31	14	14
PVRL1	0.022	0.038	-10000	0	-0.46	3	3
PVRL3	0.008	0.086	-10000	0	-0.44	18	18
PVRL2	0.027	0.005	-10000	0	-10000	0	0
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
CDH1	0.021	0.053	-10000	0	-0.46	6	6
CLDN1	0.002	0.091	-10000	0	-0.44	20	20
JAM-A/CLDN1	0.029	0.081	-10000	0	-0.25	31	31
SRC	0.003	0.12	-10000	0	-0.5	15	15
ITGB3	0.01	0.087	-10000	0	-0.41	21	21
nectin-1(dimer)/I-afadin/I-afadin	0.035	0.031	-10000	0	-0.33	3	3
FARP2	0.02	0.16	-10000	0	-0.56	21	21
RAC1	0.026	0.007	-10000	0	-10000	0	0
CTNNA1	0.027	0.006	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.036	0.061	-10000	0	-0.26	18	18
nectin-1/I-afadin	0.035	0.031	-10000	0	-0.33	3	3
nectin-2/I-afadin	0.039	0.01	-10000	0	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0.035	0.011	-10000	0	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.032	0.066	-10000	0	-0.27	21	21
CDC42/GTP/IQGAP1/filamentous actin	0.036	0.008	-10000	0	-10000	0	0
F11R	0.027	0.022	-10000	0	-0.46	1	1
positive regulation of filopodium formation	0.01	0.092	-10000	0	-0.32	19	19
alphaV/beta3 Integrin/Talin	0.045	0.089	0.26	15	-0.32	7	22
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.039	0.01	-10000	0	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.039	0.01	-10000	0	-10000	0	0
PIP5K1C	0.001	0.038	-10000	0	-0.36	3	3
VAV2	0.034	0.13	0.31	1	-0.5	13	14
RAP1/GDP	0.043	0.11	0.3	5	-0.38	12	17
ITGAV	0.025	0.027	-10000	0	-0.39	2	2
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.036	0.061	-10000	0	-0.26	18	18
nectin-3(dimer)/I-afadin/I-afadin	0.023	0.066	-10000	0	-0.31	18	18
Rac1/GTP	0.03	0.1	-10000	0	-0.38	14	14
PTPRM	0.005	0.043	-10000	0	-0.23	13	13
E-cadherin/beta catenin/alpha catenin	0.062	0.054	-10000	0	-0.44	2	2
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.027	0.005	-10000	0	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.027	0.005	-10000	0	-10000	0	0
HDAC3	0.027	0.006	-10000	0	-10000	0	0
VDR	0.026	0.031	-10000	0	-0.46	2	2
Cbp/p300/PCAF	0.035	0.069	-10000	0	-0.29	19	19
EP300	0.026	0.022	-10000	0	-0.46	1	1
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.003	0.086	-10000	0	-0.41	12	12
KAT2B	0.007	0.092	-10000	0	-0.46	19	19
MAPK14	0.027	0.006	-10000	0	-10000	0	0
AKT1	-0.013	0.092	0.19	4	-0.27	28	32
RAR alpha/9cRA/Cyclin H	0.035	0.061	0.22	1	-0.38	1	2
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	-0.015	0.11	-10000	0	-0.37	26	26
CDC2	0	0.001	-10000	0	-10000	0	0
response to UV	0.001	0.001	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.013	0.059	-10000	0	-0.35	7	7
NCOR2	0.028	0.004	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.019	0.022	-10000	0	-0.33	2	2
RXRs/RARs/NRIP1/9cRA	-0.018	0.12	0.28	1	-0.53	11	12
NCOA2	-0.009	0.12	-10000	0	-0.46	36	36
NCOA3	0.027	0.006	-10000	0	-10000	0	0
NCOA1	0.028	0.003	-10000	0	-10000	0	0
VDR/VDR/DNA	0.026	0.031	-10000	0	-0.46	2	2
RARG	0.027	0.022	-10000	0	-0.46	1	1
RAR gamma1/9cRA	0.037	0.015	-10000	0	-0.28	1	1
MAPK3	0.028	0.005	-10000	0	-10000	0	0
MAPK1	0.027	0.005	-10000	0	-10000	0	0
MAPK8	0.022	0.053	-10000	0	-0.46	6	6
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.011	0.088	-10000	0	-0.48	5	5
RARA	0.005	0.043	-10000	0	-0.22	6	6
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.03	0.13	-10000	0	-0.44	36	36
PRKCA	0.028	0.03	-10000	0	-0.43	2	2
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.028	0.13	-10000	0	-0.52	17	17
RXRG	-0.034	0.12	-10000	0	-0.33	57	57
RXRA	0.008	0.048	-10000	0	-0.28	2	2
RXRB	0.002	0.061	-10000	0	-0.32	5	5
VDR/Vit D3/DNA	0.019	0.022	-10000	0	-0.33	2	2
RBP1	-0.048	0.16	-10000	0	-0.39	88	88
CRBP1/9-cic-RA	-0.033	0.11	-10000	0	-0.27	88	88
RARB	-0.008	0.12	-10000	0	-0.46	36	36
PRKCG	-0.02	0.13	-10000	0	-0.38	58	58
MNAT1	0.026	0.007	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.014	0.11	0.31	1	-0.47	8	9
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.009	0.1	-10000	0	-0.44	9	9
proteasomal ubiquitin-dependent protein catabolic process	-0.024	0.12	0.22	1	-0.37	35	36
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.028	0.14	-10000	0	-0.52	17	17
positive regulation of DNA binding	0.026	0.054	-10000	0	-0.36	1	1
NRIP1	-0.033	0.16	0.34	1	-0.76	10	11
RXRs/RARs	-0.034	0.14	-10000	0	-0.52	20	20
RXRs/RXRs/DNA/9cRA	-0.004	0.077	-10000	0	-0.46	5	5
PRKACA	0.028	0.004	-10000	0	-10000	0	0
CDK7	0.027	0.006	-10000	0	-10000	0	0
TFIIH	0.051	0.018	-10000	0	-10000	0	0
RAR alpha/9cRA	0.042	0.052	-10000	0	-10000	0	0
CCNH	0.026	0.007	-10000	0	-10000	0	0
CREBBP	0.027	0.004	-10000	0	-10000	0	0
RAR gamma2/9cRA	0.047	0.024	-10000	0	-10000	0	0

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	0.02	0.032	-10000	0	-0.25	6	6
epithelial cell differentiation	0.048	0.037	-10000	0	-0.24	5	5
CYFIP2	0.025	0.029	-10000	0	-0.42	2	2
ENAH	0.019	0.07	0.23	11	-0.46	1	12
EGFR	0.02	0.044	-10000	0	-0.46	4	4
EPHA2	0.021	0.053	-10000	0	-0.46	6	6
MYO6	0.017	0.036	0.21	2	-10000	0	2
CTNNB1	0.024	0.009	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.05	0.026	-10000	0	-0.26	2	2
AQP5	-0.27	0.22	-10000	0	-0.46	271	271
CTNND1	0.028	0.003	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.017	0.037	0.21	2	-10000	0	2
regulation of calcium-dependent cell-cell adhesion	0.001	0.062	-10000	0	-10000	0	0
EGF	-0.067	0.19	-10000	0	-0.46	98	98
NCKAP1	0.027	0.005	-10000	0	-10000	0	0
AQP3	-0.092	0.19	-10000	0	-0.46	88	88
cortical microtubule organization	0.048	0.037	-10000	0	-0.24	5	5
GO:0000145	-0.002	0.037	0.2	3	-10000	0	3
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.052	0.039	-10000	0	-0.24	5	5
MLLT4	0.027	0.005	-10000	0	-10000	0	0
ARF6/GDP	-0.012	0.028	-10000	0	-0.4	1	1
ARF6	0.026	0.007	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.053	0.041	-10000	0	-0.26	4	4
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.007	0.03	0.21	1	-10000	0	1
PVRL2	0.027	0.005	-10000	0	-10000	0	0
ZYX	0.016	0.036	0.21	2	-10000	0	2
ARF6/GTP	0.057	0.044	-10000	0	-0.24	4	4
CDH1	0.021	0.053	-10000	0	-0.46	6	6
EGFR/EGFR/EGF/EGF	-0.01	0.11	-10000	0	-0.39	4	4
RhoA/GDP	0.049	0.036	-10000	0	-10000	0	0
actin cytoskeleton organization	-0.002	0.036	0.19	2	-10000	0	2
IGF-1R heterotetramer	0.027	0.005	-10000	0	-10000	0	0
GIT1	0.028	0.003	-10000	0	-10000	0	0
IGF1R	0.027	0.005	-10000	0	-10000	0	0
IGF1	-0.053	0.18	-10000	0	-0.46	85	85
DIAPH1	0.019	0.12	-10000	0	-10000	0	0
Wnt receptor signaling pathway	-0.048	0.037	0.24	5	-10000	0	5
RHOA	0.025	0.009	-10000	0	-10000	0	0
RhoA/GTP	-0.012	0.028	-10000	0	-0.4	1	1
CTNNA1	0.027	0.006	-10000	0	-10000	0	0
VCL	-0.002	0.037	0.2	2	-10000	0	2
EFNA1	0.027	0.004	-10000	0	-10000	0	0
LPP	-0.003	0.031	0.2	2	-10000	0	2
Ephrin A1/EPHA2	0.039	0.045	-10000	0	-0.44	1	1
SEC6/SEC8	0.01	0.021	-10000	0	-10000	0	0
MGAT3	0.001	0.062	-10000	0	-10000	0	0
HGF/MET	0.029	0.067	-10000	0	-0.38	3	3
HGF	0.006	0.095	-10000	0	-0.44	22	22
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.02	0.032	-10000	0	-0.25	6	6
actin cable formation	0.058	0.095	0.23	81	-0.33	1	82
KIAA1543	-0.014	0.064	0.2	3	-0.38	4	7
KIFC3	0.014	0.032	-10000	0	-10000	0	0
NCK1	0.023	0.011	-10000	0	-10000	0	0
EXOC3	0.024	0.01	-10000	0	-10000	0	0
ACTN1	0.016	0.036	0.21	2	-10000	0	2
NCK1/GIT1	0.034	0.016	-10000	0	-10000	0	0
mol:GDP	0.048	0.037	-10000	0	-0.24	5	5
EXOC4	0.026	0.007	-10000	0	-10000	0	0
STX4	0.017	0.037	0.21	2	-10000	0	2
PIP5K1C	0.017	0.038	0.21	2	-10000	0	2
LIMA1	0.028	0.003	-10000	0	-10000	0	0
ABI1	0.027	0.005	-10000	0	-10000	0	0
ROCK1	0.025	0.078	0.27	10	-0.35	1	11
adherens junction assembly	-0.01	0.096	0.28	6	-0.5	8	14
IGF-1R heterotetramer/IGF1	0.002	0.1	-10000	0	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.039	0.01	-10000	0	-10000	0	0
MET	0.022	0.048	-10000	0	-0.41	6	6
PLEKHA7	0.003	0.07	0.21	2	-0.4	4	6
mol:GTP	0.052	0.04	-10000	0	-0.26	4	4
establishment of epithelial cell apical/basal polarity	0.024	0.082	0.33	12	-10000	0	12
cortical actin cytoskeleton stabilization	0.02	0.032	-10000	0	-0.25	6	6
regulation of cell-cell adhesion	-0.002	0.036	0.19	2	-10000	0	2
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.02	0.032	-10000	0	-0.25	6	6

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.042	0.15	-9999	-0.39	85	85
mol:S1P	0.001	0.002	-9999	-10000	0	0
S1P1/S1P/Gi	0.006	0.06	-9999	-0.25	13	13
GNAO1	0.024	0.04	-9999	-0.42	4	4
S1P/S1P3/G12/G13	0.045	0.039	-9999	-0.24	7	7
AKT1	-0.005	0.11	-9999	-0.48	19	19
AKT3	0.019	0.088	-9999	-0.66	1	1
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.042	0.15	-9999	-0.39	85	85
GNAI2	0.025	0.011	-9999	-10000	0	0
GNAI3	0.028	0.007	-9999	-10000	0	0
GNAI1	0.026	0.023	-9999	-0.46	1	1
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.022	0.052	-9999	-0.45	6	6
S1PR2	0.027	0.004	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.021	0.065	-9999	-0.32	10	10
MAPK3	0.016	0.059	-9999	-0.32	8	8
MAPK1	0.013	0.059	-9999	-0.31	9	9
JAK2	0.016	0.08	-9999	-0.42	8	8
CXCR4	0.009	0.076	-9999	-0.33	12	12
FLT1	0.027	0.021	-9999	-0.38	1	1
RhoA/GDP	0.018	0.007	-9999	-10000	0	0
Rac1/GDP	0.019	0.005	-9999	-10000	0	0
SRC	0.015	0.059	-9999	-0.35	6	6
S1P/S1P3/Gi	0.021	0.065	-9999	-0.32	10	10
RAC1	0.026	0.007	-9999	-10000	0	0
RhoA/GTP	0.026	0.07	-9999	-0.34	5	5
VEGFA	0.023	0.045	-9999	-0.38	6	6
S1P/S1P2/Gi	0.024	0.048	-9999	-0.27	5	5
VEGFR1 homodimer/VEGFA homodimer	0.038	0.04	-9999	-0.27	7	7
RHOA	0.025	0.009	-9999	-10000	0	0
S1P/S1P3/Gq	-0.013	0.1	-9999	-0.24	77	77
GNAQ	0.027	0.005	-9999	-10000	0	0
GNAZ	0.013	0.08	-9999	-0.41	17	17
G12/G13	0.037	0.018	-9999	-0.27	1	1
GNA14	-0.041	0.17	-9999	-0.46	71	71
GNA15	0.025	0.031	-9999	-0.46	2	2
GNA12	0.025	0.02	-9999	-0.39	1	1
GNA13	0.028	0.003	-9999	-10000	0	0
GNA11	0.024	0.038	-9999	-0.46	3	3
Rac1/GTP	0.021	0.072	-9999	-0.34	6	6

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0.011	0.089	-10000	0	-0.24	56	56
MAPK9	0.008	0.002	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.009	0.006	-10000	0	-10000	0	0
GNB1/GNG2	0.035	0.011	-10000	0	-10000	0	0
GNB1	0.027	0.006	-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	0.008	0.002	-10000	0	-10000	0	0
Gs family/GTP	-0.014	0.086	-10000	0	-0.25	59	59
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	0.008	0.022	0.068	59	-10000	0	59
GNAL	-0.03	0.16	-10000	0	-0.46	59	59
GNG2	0.026	0.007	-10000	0	-10000	0	0
CRH	-0.014	0.012	-10000	0	-10000	0	0
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.004	0.034	-10000	0	-0.31	6	6
MAPK11	0.008	0.001	-10000	0	-10000	0	0

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.046	0.079	0.34	1	-0.41	1	2
CRKL	0.021	0.082	0.31	6	-0.31	1	7
mol:DAG	0.021	0.062	-10000	0	-0.29	1	1
HRAS	0.026	0.084	0.3	14	-10000	0	14
MAPK8	0.022	0.098	0.22	9	-0.3	6	15
RAP1A	0.023	0.083	0.31	7	-0.31	1	8
GAB1	0.023	0.083	0.31	7	-0.31	1	8
MAPK14	0.024	0.093	0.2	42	-0.36	2	44
EPO	-0.014	0.12	-10000	0	-0.38	51	51
PLCG1	0.021	0.063	-10000	0	-0.3	1	1
EPOR/TRPC2/IP3 Receptors	0.019	0.06	-10000	0	-0.38	10	10
RAPGEF1	0.027	0.005	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.024	0.089	-10000	0	-0.22	48	48
GAB1/SHC/GRB2/SOS1	0.05	0.08	0.27	6	-10000	0	6
EPO/EPOR (dimer)	0.007	0.1	-10000	0	-0.27	58	58
IRS2	0.022	0.084	0.31	7	-0.31	1	8
STAT1	0.021	0.069	-10000	0	-0.34	1	1
STAT5B	0.024	0.066	-10000	0	-0.34	1	1
cell proliferation	0.015	0.097	0.2	50	-0.34	2	52
GAB1/SHIP/PIK3R1/SHP2/SHC	0.031	0.073	-10000	0	-0.34	2	2
TEC	0.012	0.098	0.29	6	-0.37	8	14
SOCS3	0.027	0.022	-10000	0	-0.46	1	1
STAT1 (dimer)	0.021	0.068	-10000	0	-0.34	1	1
JAK2	0.022	0.02	-10000	0	-10000	0	0
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
EPO/EPOR (dimer)/JAK2	0.046	0.085	-10000	0	-0.33	1	1
EPO/EPOR	0.007	0.1	-10000	0	-0.27	58	58
LYN	0.025	0.021	-10000	0	-0.39	1	1
TEC/VAV2	0.016	0.1	0.28	2	-0.39	11	13
elevation of cytosolic calcium ion concentration	0.019	0.059	-10000	0	-0.38	10	10
SHC1	0.028	0.004	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	0.024	0.087	-10000	0	-0.42	2	2
mol:IP3	0.021	0.062	-10000	0	-0.29	1	1
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.043	0.089	0.31	6	-0.36	2	8
SH2B3	0.026	0.027	-10000	0	-0.39	1	1
NFKB1	0.024	0.094	0.2	35	-0.36	2	37
EPO/EPOR (dimer)/JAK2/SOCS3	-0.003	0.051	-10000	0	-0.24	11	11
PTPN6	0.02	0.081	0.3	4	-0.32	1	5
TEC/VAV2/GRB2	0.025	0.11	0.29	2	-0.38	11	13
EPOR	0.019	0.06	-10000	0	-0.38	10	10
INPP5D	0.025	0.031	-10000	0	-0.46	2	2
mol:GDP	0.049	0.081	0.27	6	-10000	0	6
SOS1	0.028	0.004	-10000	0	-10000	0	0
PLCG2	0.025	0.023	-10000	0	-0.46	1	1
CRKL/CBL/C3G	0.036	0.078	0.29	2	-0.3	1	3
VAV2	0.018	0.091	0.31	7	-0.33	4	11
CBL	0.021	0.081	0.31	7	-0.31	1	8
SHC/Grb2/SOS1	0.021	0.063	-10000	0	-0.3	1	1
STAT5A	0.024	0.066	-10000	0	-0.34	1	1
GRB2	0.027	0.004	-10000	0	-10000	0	0
STAT5 (dimer)	0.04	0.076	-10000	0	-0.38	1	1
LYN/PLCgamma2	0.034	0.026	-10000	0	-0.3	2	2
PTPN11	0.028	0.002	-10000	0	-10000	0	0
BTK	0.022	0.083	0.31	6	-0.31	1	7
BCL2	0.04	0.11	0.34	1	-0.71	5	6

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0.008	0.043	0.13	56	-0.12	1	57
BUB1B	0.01	0.03	0.12	4	-0.15	3	7
PLK1	0.01	0.025	0.087	19	-10000	0	19
PLK1S1	0.013	0.026	0.11	10	-0.18	4	14
KIF2A	0.008	0.022	0.19	1	-10000	0	1
regulation of mitotic centrosome separation	0.01	0.025	0.086	19	-10000	0	19
GOLGA2	0.027	0.005	-10000	0	-10000	0	0
Hec1/SPC24	0.033	0.043	-10000	0	-0.22	6	6
WEE1	0.009	0.065	-10000	0	-0.3	18	18
cytokinesis	0.009	0.051	-10000	0	-0.22	2	2
PP2A-alpha B56	0.06	0.049	-10000	0	-0.53	3	3
AURKA	0.011	0.029	0.11	2	-0.18	7	9
PICH/PLK1	0.016	0.04	0.17	4	-10000	0	4
CENPE	0.008	0.021	-10000	0	-10000	0	0
RhoA/GTP	0.018	0.007	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.008	0.023	0.19	1	-10000	0	1
PPP2CA	0.027	0.006	-10000	0	-10000	0	0
FZR1	0.027	0.005	-10000	0	-10000	0	0
TPX2	0.016	0.025	0.11	14	-0.16	2	16
PAK1	0.025	0.009	-10000	0	-10000	0	0
SPC24	0.019	0.06	-10000	0	-0.39	11	11
FBXW11	0.027	0.006	-10000	0	-10000	0	0
CLSPN	0.01	0.032	-10000	0	-0.24	6	6
GORASP1	0.024	0.009	-10000	0	-10000	0	0
metaphase	0	0.002	0.015	8	-0.011	3	11
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.005	0.014	0.048	21	-10000	0	21
G2 phase of mitotic cell cycle	-0.001	0.002	0.014	1	-10000	0	1
STAG2	0.028	0.004	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	-0.042	0.18	-10000	0	-0.5	66	66
spindle elongation	0.01	0.025	0.086	19	-10000	0	19
ODF2	0.028	0.005	-10000	0	-10000	0	0
BUB1	0.028	0.048	-10000	0	-0.58	3	3
TPT1	0.001	0.049	-10000	0	-0.18	32	32
CDC25C	0.001	0.064	-10000	0	-0.27	24	24
CDC25B	0.014	0.072	-10000	0	-0.39	16	16
SGOL1	-0.008	0.044	0.12	1	-0.13	56	57
RHOA	0.025	0.009	-10000	0	-10000	0	0
CCNB1/CDK1	0.031	0.045	-10000	0	-0.23	2	2
CDC14B	0.006	0.021	-10000	0	-0.34	2	2
CDC20	0.019	0.06	-10000	0	-0.39	11	11
PLK1/PBIP1	0.009	0.021	0.092	1	-0.15	2	3
mitosis	-0.001	0.005	0.023	11	-10000	0	11
FBXO5	0.009	0.025	0.12	7	-10000	0	7
CDC2	0.001	0.002	-10000	0	-0.014	2	2
NDC80	0.024	0.02	-10000	0	-0.39	1	1
metaphase plate congression	0.007	0.047	-10000	0	-0.24	17	17
ERCC6L	0.014	0.042	-10000	0	-10000	0	0
NLP/gamma Tubulin	0.008	0.017	0.063	10	-0.11	2	12
microtubule cytoskeleton organization	0.001	0.049	-10000	0	-0.18	32	32
G2/M transition DNA damage checkpoint	0	0.003	0.014	10	-10000	0	10
PPP1R12A	0.028	0.003	-10000	0	-10000	0	0
interphase	0	0.003	0.014	10	-10000	0	10
PLK1/PRC1-2	0.04	0.027	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP/PLK1	0.044	0.03	-10000	0	-10000	0	0
RAB1A	0.028	0.003	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.009	0.022	0.085	20	-10000	0	20
mitotic prometaphase	0	0.003	0.017	17	-10000	0	17
proteasomal ubiquitin-dependent protein catabolic process	0.019	0.058	-10000	0	-0.48	5	5
microtubule-based process	0.026	0.024	-10000	0	-10000	0	0
Golgi organization	0.01	0.025	0.086	19	-10000	0	19
Cohesin/SA2	0.023	0.021	-10000	0	-10000	0	0
PPP1CB/MYPT1	0.041	0.007	-10000	0	-10000	0	0
KIF20A	0.027	0.006	-10000	0	-10000	0	0
APC/C/CDC20	0.022	0.039	-10000	0	-0.19	10	10
PPP2R1A	0.027	0.004	-10000	0	-10000	0	0
chromosome segregation	0.009	0.02	0.091	1	-0.15	2	3
PRC1	0.027	0.004	-10000	0	-10000	0	0
ECT2	0.067	0.098	0.22	146	-10000	0	146
C13orf34	0.009	0.022	0.078	20	-10000	0	20
NUDC	0.007	0.047	-10000	0	-0.24	17	17
regulation of attachment of spindle microtubules to kinetochore	0.01	0.03	0.12	5	-0.15	3	8
spindle assembly	0.009	0.021	0.076	16	-10000	0	16
spindle stabilization	0.013	0.026	0.11	10	-0.18	4	14
APC/C/HCDH1	0.023	0.02	-10000	0	-0.27	2	2
MKLP2/PLK1	0.026	0.024	-10000	0	-10000	0	0
CCNB1	0.027	0.007	-10000	0	-10000	0	0
PPP1CB	0.028	0.004	-10000	0	-10000	0	0
BTRC	0.027	0.004	-10000	0	-10000	0	0
ROCK2	-0.002	0.074	-10000	0	-0.35	14	14
TUBG1	0.012	0.022	-10000	0	-0.21	3	3
G2/M transition of mitotic cell cycle	0.005	0.034	-10000	0	-0.23	2	2
MLF1IP	0.006	0.018	-10000	0	-0.28	2	2
INCENP	0.028	0.004	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	0.014	0.005	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.037	0.021	-10000	0	-10000	0	0
CDKN1B	0.017	0.062	-10000	0	-0.29	1	1
CDKN1A	0.016	0.052	-10000	0	-0.28	11	11
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.025	0.009	-10000	0	-10000	0	0
FOXO3	0.013	0.055	-10000	0	-0.28	9	9
AKT1	0.01	0.046	-10000	0	-0.29	8	8
BAD	0.027	0.005	-10000	0	-10000	0	0
AKT3	0.012	0.024	-10000	0	-0.3	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.013	0.058	-10000	0	-0.28	9	9
AKT1/ASK1	0.039	0.066	-10000	0	-0.27	9	9
BAD/YWHAZ	0.047	0.022	-10000	0	-10000	0	0
RICTOR	0.025	0.009	-10000	0	-10000	0	0
RAF1	0.025	0.009	-10000	0	-10000	0	0
JNK cascade	-0.036	0.063	0.27	9	-10000	0	9
TSC1	0.013	0.055	-10000	0	-0.28	13	13
YWHAZ	0.024	0.01	-10000	0	-10000	0	0
AKT1/RAF1	0.04	0.072	0.28	3	-0.28	6	9
EP300	0.026	0.022	-10000	0	-0.46	1	1
mol:GDP	0.015	0.058	-10000	0	-0.29	13	13
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.014	0.054	-10000	0	-0.29	1	1
YWHAQ	0.028	0.003	-10000	0	-10000	0	0
TBC1D4	0.008	0.012	-10000	0	-0.26	1	1
MAP3K5	0.027	0.005	-10000	0	-10000	0	0
MAPKAP1	0.027	0.005	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.041	0.07	0.28	9	-0.2	15	24
YWHAH	0.027	0.004	-10000	0	-10000	0	0
AKT1S1	0.015	0.052	-10000	0	-0.28	7	7
CASP9	0.015	0.046	-10000	0	-10000	0	0
YWHAB	0.026	0.007	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.047	0.072	0.3	10	-10000	0	10
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.049	0.024	-10000	0	-0.28	1	1
YWHAE	0.027	0.006	-10000	0	-10000	0	0
SRC	0.026	0.007	-10000	0	-10000	0	0
AKT2/p21CIP1	0.02	0.056	-10000	0	-0.3	2	2
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.002	0.081	-10000	0	-0.33	25	25
CHUK	0.014	0.053	-10000	0	-0.29	1	1
BAD/BCL-XL	0.044	0.064	0.26	1	-10000	0	1
mTORC2	0.031	0.013	-10000	0	-10000	0	0
AKT2	0.014	0.014	-10000	0	-0.3	1	1
FOXO1-3a-4/14-3-3 family	0.049	0.09	0.25	13	-0.39	8	21
PDPK1	0.027	0.022	-10000	0	-0.46	1	1
MDM2	0.017	0.062	-10000	0	-0.28	8	8
MAPKKK cascade	-0.04	0.071	0.28	6	-0.28	3	9
MDM2/Cbp/p300	0.062	0.078	0.27	10	-10000	0	10
TSC1/TSC2	0.015	0.057	0.29	4	-10000	0	4
proteasomal ubiquitin-dependent protein catabolic process	0.059	0.075	0.26	10	-10000	0	10
glucose import	-0.094	0.12	0.21	6	-0.24	208	214
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.01	0.061	0.18	1	-0.34	7	8
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.096	0.12	0.21	4	-0.24	208	212
GSK3A	0.015	0.053	-10000	0	-0.28	7	7
FOXO1	0.014	0.05	-10000	0	-0.28	7	7
GSK3B	0.029	0.064	-10000	0	-0.28	6	6
SFN	0.024	0.04	-10000	0	-0.42	4	4
G1/S transition of mitotic cell cycle	0.041	0.067	0.25	8	-10000	0	8
p27Kip1/14-3-3 family	0.03	0.062	-10000	0	-0.43	3	3
PRKACA	0.028	0.004	-10000	0	-10000	0	0
KPNA1	0.025	0.009	-10000	0	-10000	0	0
HSP90AA1	0.026	0.007	-10000	0	-10000	0	0
YWHAG	0.027	0.006	-10000	0	-10000	0	0
RHEB	0.026	0.007	-10000	0	-10000	0	0
CREBBP	0.027	0.004	-10000	0	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.014	0.097	0.28	5	-0.46	9	14
BAG4	0.023	0.023	-10000	0	-0.46	1	1
BAD	0.016	0.049	0.19	15	-0.21	1	16
NFKBIA	0.026	0.007	-10000	0	-10000	0	0
BIRC3	0.012	0.071	-10000	0	-0.39	15	15
BAX	0.013	0.042	0.17	8	-0.18	3	11
EnzymeConsortium:3.1.4.12	0.007	0.026	0.074	8	-0.096	9	17
IKBKB	0.025	0.097	0.3	11	-0.46	7	18
MAP2K2	0.015	0.043	0.19	11	-10000	0	11
MAP2K1	0.015	0.044	0.19	10	-10000	0	10
SMPD1	0.008	0.035	0.13	5	-0.14	10	15
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.064	0.12	0.28	42	-0.45	6	48
MAP2K4	0.013	0.041	0.19	6	-10000	0	6
protein ubiquitination	0.022	0.1	0.28	9	-0.46	8	17
EnzymeConsortium:2.7.1.37	0.015	0.047	0.19	10	-10000	0	10
response to UV	0	0	0.002	10	-10000	0	10
RAF1	0.014	0.042	0.2	9	-0.19	1	10
CRADD	0.028	0.002	-10000	0	-10000	0	0
mol:ceramide	0.013	0.042	0.12	10	-0.15	8	18
I-kappa-B-alpha/RELA/p50/ubiquitin	0.034	0.012	-10000	0	-10000	0	0
MADD	0.027	0.005	-10000	0	-10000	0	0
MAP3K1	0.013	0.04	0.18	4	-0.19	2	6
TRADD	0.027	0.006	-10000	0	-10000	0	0
RELA/p50	0.026	0.006	-10000	0	-10000	0	0
MAPK3	0.017	0.048	0.19	9	-0.22	1	10
MAPK1	0.017	0.045	0.19	9	-10000	0	9
p50/RELA/I-kappa-B-alpha	0.037	0.013	-10000	0	-10000	0	0
FADD	0.055	0.12	0.27	30	-0.45	7	37
KSR1	0.014	0.045	0.18	10	-0.19	2	12
MAPK8	0.011	0.045	0.18	9	-0.24	1	10
TRAF2	0.023	0.041	-10000	0	-0.39	5	5
response to radiation	0	0	0.002	3	-10000	0	3
CHUK	0.016	0.094	0.29	4	-0.46	7	11
TNF R/SODD	0.033	0.023	-10000	0	-0.33	1	1
TNF	0.008	0.088	-10000	0	-0.4	23	23
CYCS	0.022	0.051	0.16	22	-10000	0	22
IKBKG	0.023	0.1	0.3	11	-0.46	7	18
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.016	0.095	-10000	0	-0.48	9	9
RELA	0.027	0.006	-10000	0	-10000	0	0
RIPK1	0.027	0.006	-10000	0	-10000	0	0
AIFM1	0.02	0.048	0.15	25	-0.16	1	26
TNF/TNF R/SODD	0.033	0.061	-10000	0	-0.24	21	21
TNFRSF1A	0.026	0.007	-10000	0	-10000	0	0
response to heat	0	0	0.002	3	-10000	0	3
CASP8	0.021	0.089	-10000	0	-0.55	11	11
NSMAF	0.027	0.11	0.27	16	-0.44	9	25
response to hydrogen peroxide	0	0	0.002	10	-10000	0	10
BCL2	0.022	0.039	-10000	0	-0.41	4	4

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.044	0.069	-10000	0	-10000	0	0
UGCG	0.001	0.12	-10000	0	-0.56	22	22
AKT1/mTOR/p70S6K/Hsp90/TERT	0.036	0.12	0.27	8	-0.42	14	22
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.003	0.12	-10000	0	-0.55	22	22
mol:DAG	0.004	0.094	-10000	0	-0.76	7	7
CaM/Ca2+/Calcineurin A alpha-beta B1	0.049	0.098	-10000	0	-0.46	5	5
FRAP1	0.046	0.11	0.29	1	-0.49	7	8
FOXO3	0.048	0.094	0.3	4	-0.39	4	8
AKT1	0.05	0.093	0.26	2	-0.4	3	5
GAB2	0.023	0.038	-10000	0	-0.46	3	3
SMPD1	0.007	0.11	-10000	0	-0.58	17	17
SGMS1	0.02	0.069	-10000	0	-0.58	6	6
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
mol:GDP	0.005	0.019	-10000	0	-0.28	2	2
CALM1	0.026	0.007	-10000	0	-10000	0	0
cell proliferation	0.046	0.089	0.26	3	-0.38	7	10
EIF3A	0.028	0.004	-10000	0	-10000	0	0
PI3K	0.029	0.031	-10000	0	-0.34	2	2
RPS6KB1	0.011	0.083	-10000	0	-0.83	2	2
mol:sphingomyelin	0.004	0.094	-10000	0	-0.76	7	7
natural killer cell activation	0	0.001	-10000	0	-0.012	1	1
JAK3	0.012	0.084	-10000	0	-0.38	22	22
PIK3R1	0.027	0.032	-10000	0	-0.46	2	2
JAK1	0.03	0.004	-10000	0	-10000	0	0
NFKB1	0.027	0.005	-10000	0	-10000	0	0
MYC	0.081	0.12	0.38	11	-10000	0	11
MYB	-0.078	0.34	-10000	0	-1.2	45	45
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.044	0.081	-10000	0	-0.33	3	3
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.036	0.083	-10000	0	-0.75	2	2
mol:PI-3-4-5-P3	0.043	0.081	-10000	0	-0.34	2	2
Rac1/GDP	0.017	0.022	-10000	0	-0.26	2	2
T cell proliferation	0.044	0.08	0.26	9	-10000	0	9
SHC1	0.028	0.004	-10000	0	-10000	0	0
RAC1	0.026	0.007	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	-0.002	0.02	-10000	0	-0.062	50	50
PRKCZ	0.042	0.078	0.24	5	-10000	0	5
NF kappa B1 p50/RelA	0.06	0.1	0.26	1	-0.44	6	7
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.016	0.051	-10000	0	-0.37	2	2
HSP90AA1	0.026	0.007	-10000	0	-10000	0	0
RELA	0.027	0.006	-10000	0	-10000	0	0
IL2RA	-0.01	0.12	-10000	0	-0.39	47	47
IL2RB	0.023	0.053	-10000	0	-0.39	8	8
TERT	-0.056	0.16	-10000	0	-0.39	97	97
E2F1	-0.011	0.14	-10000	0	-0.42	46	46
SOS1	0.028	0.004	-10000	0	-10000	0	0
RPS6	0.025	0.009	-10000	0	-10000	0	0
mol:cAMP	0.001	0.01	0.03	50	-10000	0	50
PTPN11	0.028	0.003	-10000	0	-10000	0	0
IL2RG	0.016	0.076	-10000	0	-0.39	17	17
actin cytoskeleton organization	0.044	0.08	0.26	9	-10000	0	9
GRB2	0.028	0.004	-10000	0	-10000	0	0
IL2	0.019	0.022	-10000	0	-0.38	1	1
PIK3CA	0.021	0.014	-10000	0	-10000	0	0
Rac1/GTP	0.035	0.033	-10000	0	-0.24	2	2
LCK	0.02	0.063	-10000	0	-0.38	12	12
BCL2	0.042	0.12	-10000	0	-0.78	6	6

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.023	0.023	-10000	0	-0.46	1	1
Caspase 8 (4 units)	0.044	0.076	-10000	0	-0.4	1	1
NEF	-0.006	0.035	-10000	0	-10000	0	0
NFKBIA	0.023	0.027	-10000	0	-10000	0	0
BIRC3	0.017	0.081	-10000	0	-0.38	14	14
CYCS	0.02	0.077	0.21	20	-0.44	1	21
RIPK1	0.027	0.006	-10000	0	-10000	0	0
CD247	0.001	0.11	-10000	0	-0.47	21	21
MAP2K7	0.033	0.14	0.32	2	-0.77	10	12
protein ubiquitination	0.041	0.096	0.24	17	-0.4	8	25
CRADD	0.028	0.002	-10000	0	-10000	0	0
DAXX	0.027	0.006	-10000	0	-10000	0	0
FAS	0.026	0.022	-10000	0	-0.46	1	1
BID	0.018	0.072	0.19	3	-0.26	11	14
NF-kappa-B/RelA/I kappa B alpha	0.044	0.07	-10000	0	-0.32	11	11
TRADD	0.027	0.006	-10000	0	-10000	0	0
MAP3K5	0.027	0.005	-10000	0	-10000	0	0
CFLAR	0.027	0.005	-10000	0	-10000	0	0
FADD	0.02	0.013	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.044	0.07	-10000	0	-0.32	11	11
MAPK8	0.03	0.13	0.29	3	-0.7	10	13
APAF1	0.028	0.002	-10000	0	-10000	0	0
TRAF1	0.017	0.065	-10000	0	-0.39	13	13
TRAF2	0.023	0.041	-10000	0	-0.39	5	5
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.025	0.076	0.2	3	-0.27	12	15
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.029	0.1	-10000	0	-0.48	11	11
CHUK	0.041	0.1	0.26	12	-0.44	8	20
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.052	0.043	-10000	0	-0.24	1	1
TCRz/NEF	-0.004	0.1	-10000	0	-0.31	48	48
TNF	0.008	0.088	-10000	0	-0.4	23	23
FASLG	-0.022	0.14	-10000	0	-0.5	40	40
NFKB1	0.024	0.028	-10000	0	-0.2	1	1
TNFR1A/BAG4/TNF-alpha	0.033	0.061	-10000	0	-0.24	21	21
CASP6	0.041	0.11	-10000	0	-0.49	14	14
CASP7	0.043	0.12	0.3	28	-0.42	7	35
RELA	0.023	0.029	-10000	0	-0.2	1	1
CASP2	0.026	0.007	-10000	0	-10000	0	0
CASP3	0.039	0.12	0.3	27	-0.41	7	34
TNFRSF1A	0.026	0.007	-10000	0	-10000	0	0
TNFR1A/BAG4	0.033	0.023	-10000	0	-0.33	1	1
CASP8	0.027	0.005	-10000	0	-10000	0	0
CASP9	0.027	0.006	-10000	0	-10000	0	0
MAP3K14	0.04	0.1	0.25	8	-0.47	9	17
APAF-1/Caspase 9	0.013	0.076	-10000	0	-0.33	3	3
BCL2	0.027	0.12	0.29	2	-0.65	10	12

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	0.036	0.009	-10000	0	-10000	0	0
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0.027	0.006	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.004	0.11	-10000	0	-0.46	25	25
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.027	0.005	-10000	0	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.009	0.023	-10000	0	-0.19	1	1
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.025	0.009	-10000	0	-10000	0	0
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	0.028	0.003	-10000	0	-10000	0	0
FYN	0.027	0.019	-10000	0	-0.39	1	1
MAP3K12	0.026	0.028	-10000	0	-0.42	2	2
FGR	0.027	0.019	-10000	0	-0.39	1	1
p38 alpha/TAB1	-0.024	0.069	-10000	0	-0.3	19	19
PRKG1	0.001	0.11	-10000	0	-0.44	28	28
DUSP8	0.027	0.006	-10000	0	-10000	0	0
PGK/cGMP/p38 alpha	0.018	0.1	0.17	4	-0.34	15	19
apoptosis	-0.023	0.066	-10000	0	-0.29	19	19
RAL/GTP	0.035	0.01	-10000	0	-10000	0	0
LYN	0.024	0.02	-10000	0	-0.39	1	1
DUSP1	0.005	0.1	-10000	0	-0.46	23	23
PAK1	0.025	0.008	-10000	0	-10000	0	0
SRC	0.026	0.007	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.061	0.036	-10000	0	-0.21	5	5
TRAF6	0.027	0.006	-10000	0	-10000	0	0
RAC1	0.026	0.007	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
mol:cGMP	0	0	-10000	0	-10000	0	0
CCM2	0.022	0.045	-10000	0	-0.39	6	6
RAC1-CDC42/GTP	0.034	0.011	-10000	0	-10000	0	0
MAPK11	0.029	0.11	0.24	22	-0.35	14	36
BLK	-0.035	0.14	-10000	0	-0.4	70	70
HCK	0.024	0.029	-10000	0	-0.42	2	2
MAP2K3	0.027	0.006	-10000	0	-10000	0	0
DUSP16	0.026	0.007	-10000	0	-10000	0	0
DUSP10	0.027	0.019	-10000	0	-0.39	1	1
TRAF6/MEKK3	0.034	0.009	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.028	0.1	0.22	22	-0.38	12	34
positive regulation of innate immune response	0.033	0.12	0.26	24	-0.41	15	39
LCK	0.018	0.063	-10000	0	-0.39	12	12
p38alpha-beta/MKP7	0.04	0.12	0.28	18	-0.4	12	30
p38alpha-beta/MKP5	0.041	0.12	0.26	21	-0.4	13	34
PGK/cGMP	0.002	0.076	-10000	0	-0.31	28	28
PAK2	0.02	0.013	-10000	0	-10000	0	0
p38alpha-beta/MKP1	0.034	0.13	0.27	23	-0.41	14	37
CDC42	0.027	0.005	-10000	0	-10000	0	0
RALB	0.027	0.004	-10000	0	-10000	0	0
RALA	0.027	0.006	-10000	0	-10000	0	0
PAK3	0.004	0.077	-10000	0	-0.39	18	18

×

Ras signaling in the CD4+ TCR 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.001	0.15	-9999	-0.47	22	22
MAP3K8	0.023	0.038	-9999	-0.46	3	3
FOS	0.002	0.11	-9999	-0.48	12	12
PRKCA	0.021	0.032	-9999	-0.42	2	2
PTPN7	0.003	0.09	-9999	-0.4	24	24
HRAS	0.026	0.02	-9999	-0.4	1	1
PRKCB	0.016	0.056	-9999	-0.41	8	8
NRAS	0.027	0.005	-9999	-10000	0	0
RAS family/GTP	0.044	0.024	-9999	-0.21	1	1
MAPK3	0.01	0.096	-9999	-0.6	8	8
MAP2K1	0.011	0.079	-9999	-0.45	9	9
ELK1	0.021	0.02	-9999	-10000	0	0
BRAF	0.012	0.044	-9999	-0.35	4	4
mol:GTP	-0.001	0.002	-9999	-0.005	66	66
MAPK1	0.013	0.081	-9999	-0.57	5	5
RAF1	0.009	0.056	-9999	-0.5	3	3
KRAS	0.026	0.007	-9999	-10000	0	0

×

Circadian rhythm pathway

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
chromatin modification	0.042	0.03	-9999	-10000	0	0
CLOCK	0.024	0.053	-9999	-0.46	6	6
TIMELESS/CRY2	0.04	0.022	-9999	-10000	0	0
DEC1/BMAL1	-0.012	0.11	-9999	-0.27	83	83
ATR	0.023	0.011	-9999	-10000	0	0
NR1D1	0.024	0.014	-9999	-10000	0	0
ARNTL	0.029	0.006	-9999	-10000	0	0
TIMELESS	0.024	0.014	-9999	-10000	0	0
NPAS2	0.023	0.057	-9999	-0.46	7	7
CRY2	0.027	0.006	-9999	-10000	0	0
mol:CO	-0.01	0	-9999	-10000	0	0
CHEK1	0.026	0.008	-9999	-10000	0	0
mol:HEME	0.01	0	-9999	-10000	0	0
PER1	0.026	0.022	-9999	-0.46	1	1
BMAL/CLOCK/NPAS2	0.056	0.057	-9999	-0.3	11	11
BMAL1/CLOCK	0.013	0.07	-9999	-0.42	1	1
S phase of mitotic cell cycle	0.042	0.03	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	0.043	0.031	-9999	-10000	0	0
mol:NADPH	0.01	0	-9999	-10000	0	0
PER1/TIMELESS	0.04	0.024	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	-0.054	0.15	-9999	-0.39	84	84

×

JNK signaling in the CD4+ TCR 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.044	0.097	-10000	0	-0.4	18	18
MAP4K1	0.015	0.07	-10000	0	-0.4	14	14
MAP3K8	0.024	0.038	-10000	0	-0.46	3	3
PRKCB	0.021	0.054	-10000	0	-0.41	8	8
DBNL	0.027	0.006	-10000	0	-10000	0	0
CRKL	0.026	0.019	-10000	0	-0.39	1	1
MAP3K1	0.012	0.058	-10000	0	-0.38	4	4
JUN	0.01	0.12	-10000	0	-0.58	18	18
MAP3K7	0.01	0.062	-10000	0	-0.37	5	5
GRAP2	0.017	0.066	-10000	0	-0.43	11	11
CRK	0.027	0.006	-10000	0	-10000	0	0
MAP2K4	0.016	0.073	0.26	9	-0.38	5	14
LAT	0.017	0.065	-10000	0	-0.39	13	13
LCP2	0.024	0.032	-10000	0	-0.39	3	3
MAPK8	0.012	0.13	-10000	0	-0.61	18	18
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.018	0.065	-10000	0	-0.35	7	7
LAT/GRAP2/SLP76/HPK1/HIP-55	0.052	0.096	-10000	0	-0.44	12	12

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	0.018	0.031	-10000	0	-0.25	2	2
CRKL	0.026	0.019	-10000	0	-0.39	1	1
Rac1/GDP	0.019	0.005	-10000	0	-10000	0	0
DOCK1	0.027	0.022	-10000	0	-0.46	1	1
ITGA4	0.021	0.051	-10000	0	-0.39	8	8
alpha4/beta7 Integrin/MAdCAM1	0.045	0.064	-10000	0	-0.26	2	2
EPO	-0.02	0.12	-10000	0	-0.39	51	51
alpha4/beta7 Integrin	0.034	0.046	-10000	0	-0.28	10	10
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.027	0.006	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.034	0.04	-10000	0	-0.27	8	8
EPO/EPOR (dimer)	0.001	0.1	-10000	0	-0.28	58	58
lamellipodium assembly	0.038	0.081	-10000	0	-0.49	3	3
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
PI3K	0.027	0.03	-10000	0	-0.33	2	2
ARF6	0.026	0.007	-10000	0	-10000	0	0
JAK2	0.004	0.058	-10000	0	-0.28	8	8
PXN	0.028	0.002	-10000	0	-10000	0	0
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
MADCAM1	0.001	0.073	-10000	0	-0.39	16	16
cell adhesion	0.043	0.063	-10000	0	-0.26	2	2
CRKL/CBL	0.035	0.02	-10000	0	-0.27	1	1
ITGB1	0.027	0.005	-10000	0	-10000	0	0
SRC	-0.004	0.08	-10000	0	-0.28	10	10
ITGB7	0.026	0.031	-10000	0	-0.46	2	2
RAC1	0.026	0.007	-10000	0	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.02	0.094	-10000	0	-0.24	55	55
p130Cas/Crk/Dock1	0.017	0.076	-10000	0	-0.35	2	2
VCAM1	-0.015	0.13	-10000	0	-0.4	51	51
RHOA	0.025	0.009	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.063	0.039	-10000	0	-0.21	8	8
BCAR1	-0.021	0.069	0.18	13	-0.37	2	15
EPOR	0.019	0.057	-10000	0	-0.39	10	10
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.025	0.008	-10000	0	-10000	0	0
GIT1	0.028	0.003	-10000	0	-10000	0	0
Rac1/GTP	0.037	0.083	-10000	0	-0.51	3	3

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.049	0.18	-10000	0	-0.61	14	14
RAD9A	0.025	0.008	-10000	0	-10000	0	0
AP1	-0.009	0.12	-10000	0	-0.33	63	63
IFNAR2	0.02	0.018	-10000	0	-10000	0	0
AKT1	0.003	0.049	-10000	0	-0.34	5	5
ER alpha/Oestrogen	0.003	0.068	-10000	0	-0.3	24	24
NFX1/SIN3/HDAC complex	0.022	0.045	-10000	0	-0.3	4	4
EGF	-0.068	0.19	-10000	0	-0.46	98	98
SMG5	0.028	0.004	-10000	0	-10000	0	0
SMG6	0.027	0.006	-10000	0	-10000	0	0
SP3/HDAC2	0.028	0.028	-10000	0	-10000	0	0
TERT/c-Abl	-0.043	0.18	-10000	0	-0.57	15	15
SAP18	0.026	0.007	-10000	0	-10000	0	0
MRN complex	0.044	0.024	-10000	0	-10000	0	0
WT1	-0.07	0.16	-10000	0	-0.39	107	107
WRN	0.025	0.008	-10000	0	-10000	0	0
SP1	0.018	0.023	-10000	0	-10000	0	0
SP3	0.026	0.007	-10000	0	-10000	0	0
TERF2IP	0.027	0.006	-10000	0	-10000	0	0
Telomerase/Nucleolin	-0.026	0.17	-10000	0	-0.57	9	9
Mad/Max	0.034	0.036	-10000	0	-0.34	4	4
TERT	-0.051	0.19	-10000	0	-0.64	13	13
CCND1	-0.005	0.2	0.49	1	-0.89	6	7
MAX	0.026	0.007	-10000	0	-10000	0	0
RBBP7	0.027	0.005	-10000	0	-10000	0	0
RBBP4	0.026	0.022	-10000	0	-0.46	1	1
TERF2	0.026	0.013	-10000	0	-10000	0	0
PTGES3	0.028	0.003	-10000	0	-10000	0	0
SIN3A	0.027	0.005	-10000	0	-10000	0	0
Telomerase/911	0.035	0.05	-10000	0	-10000	0	0
CDKN1B	-0.023	0.095	-10000	0	-10000	0	0
RAD1	0.025	0.009	-10000	0	-10000	0	0
XRCC5	0.027	0.006	-10000	0	-10000	0	0
XRCC6	0.027	0.004	-10000	0	-10000	0	0
SAP30	0.026	0.019	-10000	0	-0.39	1	1
TRF2/PARP2	0.038	0.015	-10000	0	-10000	0	0
UBE3A	0.027	0.005	-10000	0	-10000	0	0
JUN	0.027	0.006	-10000	0	-10000	0	0
E6	-0.001	0.003	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.014	0.015	-10000	0	-10000	0	0
FOS	-0.034	0.16	-10000	0	-0.46	63	63
IFN-gamma/IRF1	-0.017	0.12	-10000	0	-0.26	95	95
PARP2	0.026	0.007	-10000	0	-10000	0	0
BLM	0.027	0.019	-10000	0	-0.39	1	1
Telomerase	0.007	0.1	-10000	0	-0.53	9	9
IRF1	0.029	0.008	-10000	0	-10000	0	0
ESR1	0.006	0.095	-10000	0	-0.42	24	24
KU/TER	0.039	0.01	-10000	0	-10000	0	0
ATM/TRF2	0.037	0.015	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.024	0.06	-10000	0	-0.4	5	5
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.026	0.06	-10000	0	-0.41	5	5
HDAC1	0.027	0.005	-10000	0	-10000	0	0
HDAC2	0.018	0.022	-10000	0	-10000	0	0
ATM	0.011	0.008	-10000	0	-10000	0	0
SMAD3	0.014	0.022	-10000	0	-0.27	3	3
ABL1	0.027	0.005	-10000	0	-10000	0	0
MXD1	0.022	0.049	-10000	0	-0.47	5	5
MRE11A	0.025	0.008	-10000	0	-10000	0	0
HUS1	0.026	0.007	-10000	0	-10000	0	0
RPS6KB1	0.028	0.003	-10000	0	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.023	0.19	-10000	0	-0.64	10	10
NR2F2	0.028	0.02	-10000	0	-0.37	1	1
MAPK3	-0.007	0.018	-10000	0	-0.27	1	1
MAPK1	-0.007	0.018	-10000	0	-0.27	1	1
TGFB1/TGF beta receptor Type II	0.025	0.032	-10000	0	-0.38	3	3
NFKB1	0.027	0.005	-10000	0	-10000	0	0
HNRNPC	0.026	0.007	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.011	0.008	-10000	0	-10000	0	0
NBN	0.025	0.009	-10000	0	-10000	0	0
EGFR	0.02	0.044	-10000	0	-0.47	4	4
mol:Oestrogen	-0.001	0.002	-10000	0	-10000	0	0
EGF/EGFR	-0.032	0.14	-10000	0	-0.34	88	88
MYC	0.021	0.012	-10000	0	-10000	0	0
IL2	0.01	0.029	-10000	0	-0.38	1	1
KU	0.039	0.01	-10000	0	-10000	0	0
RAD50	0.026	0.007	-10000	0	-10000	0	0
HSP90AA1	0.026	0.007	-10000	0	-10000	0	0
TGFB1	0.025	0.032	-10000	0	-0.39	3	3
TRF2/BLM	0.039	0.019	-10000	0	-0.26	1	1
FRAP1	0	0	-10000	0	-10000	0	0
KU/TERT	-0.031	0.18	-10000	0	-0.59	12	12
SP1/HDAC2	0.028	0.033	-10000	0	-10000	0	0
PINX1	0.025	0.008	-10000	0	-10000	0	0
Telomerase/EST1A	-0.026	0.17	-10000	0	-0.58	9	9
Smad3/Myc	0.024	0.021	-10000	0	-0.22	2	2
911 complex	0.043	0.025	-10000	0	-10000	0	0
IFNG	-0.05	0.16	-10000	0	-0.38	97	97
Telomerase/PinX1	-0.026	0.17	-10000	0	-0.58	9	9
Telomerase/AKT1/mTOR/p70S6K	0.001	0.096	0.26	1	-0.47	8	9
SIN3B	0.027	0.003	-10000	0	-10000	0	0
YWHAE	0.027	0.006	-10000	0	-10000	0	0
Telomerase/EST1B	-0.025	0.17	-10000	0	-0.58	9	9
response to DNA damage stimulus	-0.002	0.028	-10000	0	-10000	0	0
MRN complex/TRF2/Rap1	0.06	0.035	-10000	0	-10000	0	0
TRF2/WRN	0.036	0.016	-10000	0	-10000	0	0
Telomerase/hnRNP C1/C2	-0.025	0.17	-10000	0	-0.59	8	8
E2F1	0.004	0.082	-10000	0	-0.4	20	20
ZNFX1	0.026	0.006	-10000	0	-10000	0	0
PIF1	0.003	0.099	-10000	0	-0.39	31	31
NCL	0.027	0.006	-10000	0	-10000	0	0
DKC1	0.027	0.006	-10000	0	-10000	0	0
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

FOXM1 transcription factor network

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
NFATC3	0.09	0.24	-10000	0	-1.1	3	3
PLK1	0.054	0.099	-10000	0	-0.68	7	7
BIRC5	0.048	0.11	-10000	0	-0.91	3	3
HSPA1B	0.089	0.24	-10000	0	-1.1	3	3
MAP2K1	0.036	0.037	-10000	0	-10000	0	0
BRCA2	0.083	0.25	-10000	0	-1.1	6	6
FOXM1	0.087	0.27	-10000	0	-1.4	3	3
XRCC1	0.088	0.24	-10000	0	-1.1	3	3
FOXM1B/p19	-0.015	0.24	-10000	0	-1.1	5	5
Cyclin D1/CDK4	0.054	0.25	-10000	0	-1.1	4	4
CDC2	0.09	0.25	-10000	0	-1.1	3	3
TGFA	0.071	0.26	0.56	1	-1.1	5	6
SKP2	0.11	0.24	0.73	1	-1.1	2	3
CCNE1	0.028	0.033	-10000	0	-0.38	3	3
CKS1B	0.088	0.24	-10000	0	-1.1	3	3
RB1	0.032	0.18	-10000	0	-0.89	6	6
FOXM1C/SP1	0.095	0.25	-10000	0	-1.2	3	3
AURKB	0.032	0.16	-10000	0	-0.77	14	14
CENPF	0.089	0.24	0.63	1	-1.1	3	4
CDK4	0.032	0.019	-10000	0	-10000	0	0
MYC	0.062	0.21	-10000	0	-0.91	3	3
CHEK2	0.035	0.037	-10000	0	-10000	0	0
ONECUT1	0.074	0.26	-10000	0	-1.1	4	4
CDKN2A	-0.13	0.19	-10000	0	-0.39	187	187
LAMA4	0.081	0.25	-10000	0	-1.1	3	3
FOXM1B/HNF6	0.072	0.28	-10000	0	-1.4	4	4
FOS	-0.006	0.44	-10000	0	-1.1	66	66
SP1	0.029	0.003	-10000	0	-10000	0	0
CDC25B	0.09	0.24	-10000	0	-1.1	3	3
response to radiation	0.015	0.023	-10000	0	-10000	0	0
CENPB	0.095	0.24	-10000	0	-1.1	3	3
CENPA	0.086	0.24	-10000	0	-1.2	3	3
NEK2	0.089	0.24	0.63	1	-1.1	3	4
HIST1H2BA	0.084	0.24	-10000	0	-1.1	3	3
CCNA2	0.03	0.021	-10000	0	-0.4	1	1
EP300	0.026	0.022	-10000	0	-0.46	1	1
CCNB1/CDK1	0.085	0.25	-10000	0	-1.3	3	3
CCNB2	0.087	0.24	0.73	1	-1.2	3	4
CCNB1	0.09	0.25	-10000	0	-1.1	3	3
ETV5	0.14	0.26	0.67	2	-1.1	3	5
ESR1	0.064	0.3	-10000	0	-1.1	16	16
CCND1	0.025	0.23	-10000	0	-1.1	4	4
GSK3A	0.036	0.034	-10000	0	-10000	0	0
Cyclin A-E1/CDK1-2	0.062	0.047	-10000	0	-0.26	1	1
CDK2	0.031	0.009	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.015	0.026	-10000	0	-10000	0	0
FOXM1B/Cbp/p300	0.094	0.24	-10000	0	-1.2	3	3
GAS1	0.085	0.26	-10000	0	-1.1	6	6
MMP2	0.073	0.25	-10000	0	-1.1	3	3
RB1/FOXM1C	0.08	0.26	0.6	1	-1.1	4	5
CREBBP	0.027	0.004	-10000	0	-10000	0	0

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.017	0.029	-10000	0	-10000	0	0
STMN1	0.01	0.049	-10000	0	-0.3	11	11
Aurora B/RasGAP/Survivin	0.042	0.077	-10000	0	-0.27	23	23
Chromosomal passenger complex/Cul3 protein complex	0.011	0.054	-10000	0	-0.27	7	7
BIRC5	0.012	0.084	-10000	0	-0.39	22	22
DES	-0.31	0.3	-10000	0	-0.56	285	285
Aurora C/Aurora B/INCENP	0.049	0.049	-10000	0	-0.22	13	13
Aurora B/TACC1	0.031	0.04	-10000	0	-0.23	10	10
Aurora B/PP2A	0.038	0.043	-10000	0	-0.26	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	0.011	0.01	-10000	0	-10000	0	0
mitotic metaphase/anaphase transition	0	0.003	-10000	0	-10000	0	0
NDC80	0.011	0.036	-10000	0	-0.27	8	8
Cul3 protein complex	0.044	0.035	-10000	0	-0.28	3	3
KIF2C	0.017	0.026	-10000	0	-0.18	2	2
PEBP1	0.028	0.003	-10000	0	-10000	0	0
KIF20A	0.026	0.006	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.037	0.047	-10000	0	-0.3	8	8
SEPT1	0.02	0.055	-10000	0	-0.39	9	9
SMC2	0.027	0.005	-10000	0	-10000	0	0
SMC4	0.021	0.012	-10000	0	-10000	0	0
NSUN2/NPM1/Nucleolin	0.006	0.12	-10000	0	-0.57	19	19
PSMA3	0.027	0.006	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.002	-10000	0	-10000	0	0
H3F3B	0.015	0.023	-10000	0	-10000	0	0
AURKB	0.027	0.056	-10000	0	-0.39	9	9
AURKC	0.021	0.051	-10000	0	-0.41	7	7
CDCA8	0.028	0.019	-10000	0	-0.39	1	1
cytokinesis	-0.001	0.058	-10000	0	-0.36	5	5
Aurora B/Septin1	0.03	0.082	-10000	0	-0.36	4	4
AURKA	0.022	0.045	-10000	0	-0.39	6	6
INCENP	0.029	0.006	-10000	0	-10000	0	0
KLHL13	0.025	0.038	-10000	0	-0.46	3	3
BUB1	0.028	0.004	-10000	0	-10000	0	0
hSgo1/Aurora B/Survivin	0.039	0.068	-10000	0	-0.24	22	22
EVI5	0.029	0.005	-10000	0	-10000	0	0
RhoA/GTP	0.051	0.053	-10000	0	-10000	0	0
SGOL1	0.025	0.009	-10000	0	-10000	0	0
CENPA	0.017	0.05	-10000	0	-0.28	5	5
NCAPG	0.026	0.007	-10000	0	-10000	0	0
Aurora B/HC8 Proteasome	0.038	0.043	-10000	0	-0.26	9	9
NCAPD2	0.026	0.007	-10000	0	-10000	0	0
Aurora B/PP1-gamma	0.039	0.042	-10000	0	-0.26	9	9
RHOA	0.025	0.009	-10000	0	-10000	0	0
NCAPH	0.027	0.004	-10000	0	-10000	0	0
NPM1	-0.008	0.11	-10000	0	-0.49	17	17
RASA1	0.024	0.031	-10000	0	-0.46	2	2
KLHL9	0.024	0.01	-10000	0	-10000	0	0
mitotic prometaphase	0	0.002	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.037	0.043	-10000	0	-0.26	9	9
PPP1CC	0.028	0.002	-10000	0	-10000	0	0
Centraspindlin	0.048	0.054	-10000	0	-10000	0	0
RhoA/GDP	0.018	0.007	-10000	0	-10000	0	0
NSUN2	0.009	0.058	-10000	0	-0.28	10	10
MYLK	0.012	0.032	-10000	0	-0.32	2	2
KIF23	0.029	0.005	-10000	0	-10000	0	0
VIM	0.01	0.046	-10000	0	-0.29	11	11
RACGAP1	0.029	0.004	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
NCL	0	0.094	-10000	0	-0.42	16	16
Chromosomal passenger complex	0.018	0.044	0.17	2	-0.24	3	5
Chromosomal passenger complex/EVI5	0.088	0.086	-10000	0	-0.36	6	6
TACC1	0.023	0.032	-10000	0	-0.46	2	2
PPP2R5D	0.027	0.006	-10000	0	-10000	0	0
CUL3	0.027	0.006	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

Sphingosine 1-phosphate (S1P) pathway

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
SPHK2	0.027	0.004	-10000	0	-10000	0	0
SPHK1	0.016	0.068	-10000	0	-0.39	14	14
GNAI2	0.024	0.009	-10000	0	-10000	0	0
mol:S1P	0.012	0.024	-10000	0	-10000	0	0
GNAO1	0.023	0.039	-10000	0	-0.41	4	4
mol:Sphinganine-1-P	0.007	0.047	-10000	0	-0.27	14	14
growth factor activity	0	0	-10000	0	-10000	0	0
S1P/S1P2/G12/G13	0.051	0.042	-10000	0	-0.23	1	1
GNAI3	0.027	0.005	-10000	0	-10000	0	0
G12/G13	0.037	0.018	-10000	0	-0.27	1	1
S1PR3	0.022	0.052	-10000	0	-0.45	6	6
S1PR2	0.027	0.004	-10000	0	-10000	0	0
EDG1	0	0	-10000	0	-10000	0	0
S1P1/S1P	0.005	0.029	-10000	0	-0.24	2	2
S1PR5	0.024	0.04	-10000	0	-0.42	4	4
S1PR4	0.004	0.096	-10000	0	-0.39	29	29
GNAI1	0.026	0.022	-10000	0	-0.46	1	1
S1P/S1P5/G12	0.036	0.043	-10000	0	-0.25	3	3
S1P/S1P3/Gq	-0.013	0.11	-10000	0	-0.38	14	14
S1P/S1P4/Gi	0.015	0.07	0.18	1	-0.38	7	8
GNAQ	0.027	0.005	-10000	0	-10000	0	0
GNAZ	0.012	0.079	-10000	0	-0.41	17	17
GNA14	-0.041	0.17	-10000	0	-0.46	71	71
GNA15	0.025	0.031	-10000	0	-0.46	2	2
GNA12	0.025	0.02	-10000	0	-0.39	1	1
GNA13	0.028	0.003	-10000	0	-10000	0	0
GNA11	0.024	0.038	-10000	0	-0.46	3	3
ABCC1	0.025	0.032	-10000	0	-0.39	3	3

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.018	0.065	-10000	0	-0.44	10	10
HRAS	0.026	0.02	-10000	0	-0.4	1	1
EGFR	0.02	0.044	-10000	0	-0.46	4	4
AKT	0.071	0.073	0.28	19	-0.26	1	20
FOXO3	0.027	0.005	-10000	0	-10000	0	0
AKT1	0.026	0.007	-10000	0	-10000	0	0
FOXO1	0.026	0.007	-10000	0	-10000	0	0
AKT3	0.022	0.048	-10000	0	-0.39	7	7
FOXO4	0.026	0.031	-10000	0	-0.46	2	2
MET	0.022	0.048	-10000	0	-0.41	6	6
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
PIK3CB	0.023	0.011	-10000	0	-10000	0	0
NRAS	0.027	0.005	-10000	0	-10000	0	0
PIK3CG	0.008	0.088	-10000	0	-0.4	22	22
PIK3R3	0.027	0.022	-10000	0	-0.46	1	1
PIK3R2	0.028	0.004	-10000	0	-10000	0	0
NF1	0.027	0.004	-10000	0	-10000	0	0
RAS	0.026	0.041	0.16	1	-0.24	3	4
ERBB2	0.027	0.004	-10000	0	-10000	0	0
proliferation/survival/translation	-0.067	0.073	0.25	6	-0.21	58	64
PI3K	0.055	0.073	0.24	31	-0.31	1	32
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
KRAS	0.026	0.007	-10000	0	-10000	0	0
FOXO	0.088	0.063	0.25	25	-10000	0	25
AKT2	0.027	0.005	-10000	0	-10000	0	0
PTEN	0.027	0.006	-10000	0	-10000	0	0

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.03	0.023	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP1	0.013	0.019	-10000	0	-0.29	1	1
mol:DAG	-0.018	0.084	-10000	0	-0.43	1	1
VEGFR1 homodimer/NRP1/VEGFR 121	0.025	0.033	-10000	0	-0.27	1	1
CaM/Ca2+	-0.004	0.084	-10000	0	-0.41	1	1
HIF1A	0.031	0.025	-10000	0	-0.45	1	1
GAB1	0.027	0.006	-10000	0	-10000	0	0
AKT1	0.021	0.098	0.35	5	-0.5	2	7
PLCG1	-0.018	0.084	-10000	0	-0.43	1	1
NOS3	0.012	0.095	0.42	6	-0.44	1	7
CBL	0.025	0.008	-10000	0	-10000	0	0
mol:NO	0.024	0.12	0.51	15	-0.4	2	17
FLT1	0.018	0.023	-10000	0	-0.34	2	2
PGF	-0.041	0.15	-10000	0	-0.39	84	84
VEGFR1 homodimer/NRP2/VEGFR121	0.04	0.039	-10000	0	-10000	0	0
CALM1	0.026	0.007	-10000	0	-10000	0	0
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
eNOS/Hsp90	0.021	0.1	0.47	3	-0.41	1	4
endothelial cell proliferation	-0.003	0.086	0.36	8	-0.42	1	9
mol:Ca2+	-0.018	0.083	-10000	0	-0.43	1	1
MAPK3	-0.023	0.087	0.34	11	-0.38	1	12
MAPK1	-0.024	0.088	0.34	11	-0.38	1	12
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
PLGF homodimer	-0.041	0.15	-10000	0	-0.39	84	84
PRKACA	0.028	0.004	-10000	0	-10000	0	0
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	-0.004	0.11	-10000	0	-0.39	38	38
VEGFA homodimer	0.022	0.045	-10000	0	-0.39	6	6
VEGFR1 homodimer/VEGFA homodimer	0.027	0.036	-10000	0	-0.3	1	1
platelet activating factor biosynthetic process	-0.024	0.083	0.33	10	-0.38	1	11
PI3K	0.011	0.085	-10000	0	-0.41	2	2
PRKCA	-0.021	0.082	0.35	4	-0.4	1	5
PRKCB	-0.022	0.086	0.35	5	-0.4	1	6
VEGFR1 homodimer/PLGF homodimer	-0.011	0.098	-10000	0	-0.38	2	2
VEGFA	0.022	0.045	-10000	0	-0.39	6	6
VEGFB	0.027	0.005	-10000	0	-10000	0	0
mol:IP3	-0.018	0.084	-10000	0	-0.43	1	1
RASA1	0.02	0.042	-10000	0	-0.48	1	1
NRP2	0.026	0.026	-10000	0	-0.39	2	2
VEGFR1 homodimer	0.018	0.023	-10000	0	-0.34	2	2
VEGFB homodimer	0.027	0.005	-10000	0	-10000	0	0
NCK1	0.023	0.011	-10000	0	-10000	0	0
eNOS/Caveolin-1	0.018	0.13	0.49	15	-0.41	2	17
PTPN11	0.028	0.002	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.01	0.084	-10000	0	-0.41	2	2
mol:L-citrulline	0.024	0.12	0.51	15	-0.4	2	17
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.051	0.04	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.035	0.037	-10000	0	-10000	0	0
CD2AP	0.027	0.006	-10000	0	-10000	0	0
PI3K/GAB1	0.019	0.087	-10000	0	-0.4	2	2
PDPK1	0.029	0.12	0.38	11	-0.5	2	13
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.041	0.038	-10000	0	-10000	0	0
mol:NADP	0.024	0.12	0.51	15	-0.4	2	17
HSP90AA1	0.026	0.007	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.049	0.039	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP2	0.03	0.027	-10000	0	-10000	0	0

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	0.012	0.13	-10000	0	-0.63	13	13
oxygen homeostasis	-0.002	0.011	-10000	0	-10000	0	0
TCEB2	0.026	0.026	-10000	0	-0.39	2	2
TCEB1	0.025	0.009	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	0.029	0.084	0.24	1	-0.43	1	2
EPO	-0.024	0.16	-10000	0	-0.57	7	7
FIH (dimer)	0.022	0.02	-10000	0	-10000	0	0
APEX1	0.021	0.023	-10000	0	-10000	0	0
SERPINE1	-0.098	0.2	-10000	0	-0.63	12	12
FLT1	-0.014	0.18	-10000	0	-0.66	28	28
ADORA2A	-0.024	0.16	0.37	3	-0.58	8	11
germ cell development	-0.032	0.17	-10000	0	-0.67	6	6
SLC11A2	-0.021	0.16	-10000	0	-0.61	7	7
BHLHE40	-0.024	0.16	-10000	0	-0.61	7	7
HIF1AN	0.022	0.02	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	0.014	0.12	0.3	1	-0.38	5	6
ETS1	0.033	0.035	-10000	0	-0.38	3	3
CITED2	0.017	0.11	-10000	0	-0.67	9	9
KDR	-0.011	0.19	-10000	0	-0.67	30	30
PGK1	-0.022	0.16	-10000	0	-0.61	7	7
SIRT1	0.026	0.022	-10000	0	-0.46	1	1
response to hypoxia	-0.001	0.003	-10000	0	-10000	0	0
HIF2A/ARNT	-0.013	0.19	-10000	0	-0.69	8	8
EPAS1	-0.003	0.078	0.22	1	-0.3	7	8
SP1	0.032	0.012	-10000	0	-10000	0	0
ABCG2	-0.027	0.17	-10000	0	-0.64	9	9
EFNA1	-0.021	0.16	-10000	0	-0.6	7	7
FXN	-0.024	0.16	0.37	3	-0.58	8	11
POU5F1	-0.034	0.17	-10000	0	-0.68	7	7
neuron apoptosis	0.013	0.18	0.67	8	-10000	0	8
EP300	0.026	0.022	-10000	0	-0.46	1	1
EGLN3	-0.001	0.099	-10000	0	-0.41	27	27
EGLN2	0.022	0.02	-10000	0	-10000	0	0
EGLN1	0.022	0.02	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.045	0.024	-10000	0	-10000	0	0
VHL	0.025	0.009	-10000	0	-10000	0	0
ARNT	0.021	0.024	-10000	0	-10000	0	0
SLC2A1	-0.027	0.17	0.37	3	-0.6	10	13
TWIST1	-0.025	0.16	0.37	3	-0.62	9	12
ELK1	0.033	0.005	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.032	0.12	0.31	1	-10000	0	1
VEGFA	-0.025	0.16	-10000	0	-0.6	8	8
CREBBP	0.027	0.004	-10000	0	-10000	0	0

×

IL2 signaling events mediated by STAT5

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
GAB2	0.023	0.038	-10000	0	-0.46	3	3
ELF1	0.009	0.075	-10000	0	-0.45	3	3
CCNA2	0.026	0.019	-10000	0	-0.39	1	1
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
JAK3	0.01	0.084	-10000	0	-0.39	22	22
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
JAK1	0.028	0.004	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.04	0.081	0.23	3	-0.37	2	5
SHC1	0.028	0.004	-10000	0	-10000	0	0
SP1	0.029	0.047	-10000	0	-0.37	6	6
IL2RA	-0.016	0.11	-10000	0	-0.35	50	50
IL2RB	0.021	0.053	-10000	0	-0.4	8	8
SOS1	0.028	0.004	-10000	0	-10000	0	0
IL2RG	0.014	0.076	-10000	0	-0.4	17	17
G1/S transition of mitotic cell cycle	0.031	0.1	0.3	5	-0.68	5	10
PTPN11	0.029	0.002	-10000	0	-10000	0	0
CCND2	0.014	0.061	-10000	0	-0.57	5	5
LCK	0.018	0.063	-10000	0	-0.39	12	12
GRB2	0.028	0.004	-10000	0	-10000	0	0
IL2	0.005	0.027	-10000	0	-0.39	1	1
CDK6	0.024	0.029	-10000	0	-0.42	2	2
CCND3	0.043	0.079	-10000	0	-10000	0	0

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.18	0.24	-10000	0	-0.46	220	220
CLTC	0.024	0.063	-10000	0	-0.35	10	10
calcium ion-dependent exocytosis	0.013	0.03	-10000	0	-10000	0	0
Dynamin 2/GTP	0.026	0.013	-10000	0	-0.21	1	1
EXOC4	0.026	0.007	-10000	0	-10000	0	0
CD59	0.015	0.031	-10000	0	-0.32	2	2
CPE	0.012	0.026	-10000	0	-0.22	6	6
CTNNB1	0.024	0.009	-10000	0	-10000	0	0
membrane fusion	0.014	0.025	-10000	0	-10000	0	0
CTNND1	0.019	0.035	0.18	20	-10000	0	20
DNM2	0.028	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.028	0.051	0.2	9	-0.4	2	11
TSHR	0.005	0.036	-10000	0	-0.23	11	11
INS	0.003	0.093	-10000	0	-0.45	19	19
BIN1	0.02	0.058	-10000	0	-0.41	9	9
mol:Choline	0.014	0.025	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.014	0.011	-10000	0	-0.23	1	1
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.026	0.007	-10000	0	-10000	0	0
mol:Ca2+	0.026	0.013	-10000	0	-0.2	1	1
JUP	0.013	0.031	-10000	0	-0.29	3	3
ASAP2/amphiphysin II	0.045	0.039	-10000	0	-0.22	9	9
ARF6/GTP	0.019	0.005	-10000	0	-10000	0	0
CDH1	0.014	0.03	-10000	0	-0.32	1	1
clathrin-independent pinocytosis	0.019	0.005	-10000	0	-10000	0	0
MAPK8IP3	0.028	0.004	-10000	0	-10000	0	0
positive regulation of endocytosis	0.019	0.005	-10000	0	-10000	0	0
EXOC2	0.026	0.007	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.022	0.031	-10000	0	-0.29	3	3
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.028	0.003	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.035	0.051	0.33	4	-10000	0	4
positive regulation of phagocytosis	0.014	0.004	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.035	0.01	-10000	0	-10000	0	0
ACAP1	0.017	0.025	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.012	0.023	-10000	0	-0.32	1	1
clathrin heavy chain/ACAP1	0.029	0.057	-10000	0	-0.4	4	4
JIP4/KLC1	0.049	0.016	-10000	0	-10000	0	0
EXOC1	0.027	0.005	-10000	0	-10000	0	0
exocyst	0.022	0.031	-10000	0	-0.29	3	3
RALA/GTP	0.02	0.005	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.035	0.01	-10000	0	-10000	0	0
receptor recycling	0.019	0.005	-10000	0	-10000	0	0
CTNNA1	0.019	0.036	0.18	22	-10000	0	22
NME1	0.014	0.011	-10000	0	-0.23	1	1
clathrin coat assembly	0.026	0.064	-10000	0	-0.35	10	10
IL2RA	0.005	0.038	-10000	0	-0.32	2	2
VAMP3	0.014	0.004	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.059	0.12	-10000	0	-0.34	9	9
EXOC6	0.027	0.004	-10000	0	-10000	0	0
PLD1	0.009	0.022	-10000	0	-0.26	3	3
PLD2	0.015	0.006	-10000	0	-10000	0	0
EXOC5	0.027	0.006	-10000	0	-10000	0	0
PIP5K1C	0.015	0.027	-10000	0	-10000	0	0
SDC1	0.014	0.029	-10000	0	-0.32	2	2
ARF6/GDP	0.024	0.013	-10000	0	-0.23	1	1
EXOC7	0.028	0.004	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.037	0.053	-10000	0	-0.34	4	4
mol:Phosphatidic acid	0.014	0.025	-10000	0	-10000	0	0
endocytosis	-0.043	0.038	0.22	9	-10000	0	9
SCAMP2	0.027	0.005	-10000	0	-10000	0	0
ADRB2	0.007	0.082	0.27	1	-0.39	6	7
EXOC3	0.024	0.01	-10000	0	-10000	0	0
ASAP2	0.028	0.004	-10000	0	-10000	0	0
Dynamin 2/GDP	0.03	0.014	-10000	0	-0.2	1	1
KLC1	0.026	0.007	-10000	0	-10000	0	0
AVPR2	0.02	0.089	0.24	13	-0.37	8	21
RALA	0.027	0.006	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.033	0.051	-10000	0	-0.37	2	2

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	0	0.11	-10000	0	-0.41	4	4
TC10/GTP	0.002	0.097	-10000	0	-0.39	1	1
Insulin Receptor/Insulin/IRS1/Shp2	0.059	0.039	-10000	0	-0.26	4	4
HRAS	0.026	0.02	-10000	0	-0.4	1	1
APS homodimer	0.025	0.02	-10000	0	-0.39	1	1
GRB14	-0.017	0.14	-10000	0	-0.45	46	46
FOXO3	0.021	0.091	-10000	0	-0.6	10	10
AKT1	0.019	0.11	0.28	7	-0.41	1	8
INSR	0.029	0.023	-10000	0	-0.46	1	1
Insulin Receptor/Insulin	0.052	0.029	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.026	0.007	-10000	0	-10000	0	0
SORBS1	-0.051	0.18	-10000	0	-0.46	82	82
CRK	0.027	0.006	-10000	0	-10000	0	0
PTPN1	0.009	0.025	-10000	0	-10000	0	0
CAV1	-0.004	0.062	0.19	1	-0.24	4	5
CBL/APS/CAP/Crk-II/C3G	0.019	0.11	-10000	0	-0.42	1	1
Insulin Receptor/Insulin/IRS1/NCK2	0.059	0.04	-10000	0	-0.26	4	4
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.034	0.037	-10000	0	-0.24	3	3
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.026	0.064	-10000	0	-0.37	6	6
RPS6KB1	0.015	0.099	0.25	9	-0.38	1	10
PARD6A	0.025	0.029	-10000	0	-0.42	2	2
CBL	0.025	0.008	-10000	0	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.021	0.011	-10000	0	-10000	0	0
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
Insulin Receptor/Insuli/IRS1/GRB2/Shc	0.036	0.085	-10000	0	-0.39	1	1
HRAS/GTP	0.016	0.027	-10000	0	-10000	0	0
Insulin Receptor	0.029	0.023	-10000	0	-0.46	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.068	0.043	-10000	0	-0.25	3	3
PRKCI	0.018	0.04	-10000	0	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	0.002	0.071	-10000	0	-0.35	2	2
SHC1	0.028	0.004	-10000	0	-10000	0	0
negative regulation of MAPKKK cascade	0.039	0.029	-10000	0	-10000	0	0
PI3K	0.042	0.043	-10000	0	-0.24	3	3
NCK2	0.028	0.003	-10000	0	-10000	0	0
RHOQ	0.028	0.004	-10000	0	-10000	0	0
mol:H2O2	0	0.003	-10000	0	-10000	0	0
HRAS/GDP	0.019	0.014	-10000	0	-0.28	1	1
AKT2	0.022	0.11	0.29	8	-0.41	1	9
PRKCZ	0.014	0.057	-10000	0	-0.43	2	2
SH2B2	0.025	0.02	-10000	0	-0.39	1	1
SHC/SHIP	0.027	0.035	-10000	0	-0.24	4	4
F2RL2	-0.084	0.18	-10000	0	-0.39	136	136
TRIP10	0.027	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insulin/Shc	0.046	0.025	-10000	0	-0.21	3	3
TC10/GTP/CIP4/Exocyst	0.037	0.008	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.072	0.033	-10000	0	-0.23	1	1
RAPGEF1	0.027	0.005	-10000	0	-10000	0	0
RASA1	0.024	0.031	-10000	0	-0.46	2	2
NCK1	0.023	0.011	-10000	0	-10000	0	0
CBL/APS/CAP/Crk-II	0.008	0.12	-10000	0	-0.26	80	80
TC10/GDP	0.02	0.003	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.059	0.032	-10000	0	-0.25	1	1
INPP5D	0.011	0.034	0.19	1	-0.24	5	6
SOS1	0.028	0.004	-10000	0	-10000	0	0
SGK1	-0.004	0.098	-10000	0	-0.63	12	12
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.028	0.002	-10000	0	-10000	0	0
IRS1	0.024	0.038	-10000	0	-0.46	3	3
p62DOK/RasGAP	0.039	0.03	-10000	0	-10000	0	0
INS	0.019	0.027	-10000	0	-0.39	2	2
mol:PI-3-4-P2	0.011	0.034	0.19	1	-0.24	5	6
GRB2	0.027	0.004	-10000	0	-10000	0	0
EIF4EBP1	0.009	0.096	0.25	9	-0.37	2	11
PTPRA	0.028	0.009	-10000	0	-10000	0	0
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
TC10/GTP/CIP4	0.037	0.008	-10000	0	-10000	0	0
PDPK1	0.027	0.022	-10000	0	-0.46	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.025	0.029	-10000	0	-0.23	1	1
Insulin Receptor/Insulin/IRS1	0.043	0.035	-10000	0	-0.24	6	6
Insulin Receptor/Insulin/IRS3	0.035	0.029	-10000	0	-0.29	3	3
Par3/Par6	-0.008	0.11	-10000	0	-0.24	8	8

×

Class IB PI3K non-lipid kinase events

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
cAMP biosynthetic process	-0.022	0.048	0.41	6	-10000	0	6
PI3K Class IB/PDE3B	0.022	0.048	-10000	0	-0.41	6	6
PDE3B	0.022	0.048	-10000	0	-0.41	6	6

×

a4b1 and a4b7 Integrin signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.027	0.005	-9999	-10000	0	0
ITGB7	0.026	0.031	-9999	-0.46	2	2
ITGA4	0.021	0.051	-9999	-0.39	8	8
alpha4/beta7 Integrin	0.034	0.046	-9999	-0.28	10	10
alpha4/beta1 Integrin	0.034	0.04	-9999	-0.27	8	8

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.026	0.008	-10000	0	-10000	0	0
NFATC1	0.024	0.094	0.25	6	-0.36	8	14
NFATC2	0.008	0.082	0.21	4	-0.31	16	20
NFATC3	0.02	0.018	-10000	0	-0.35	1	1
YWHAE	0.027	0.006	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.001	0.078	0.2	5	-0.29	14	19
Exportin 1/Ran/NUP214	0.054	0.014	-10000	0	-10000	0	0
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	0.015	0.088	-10000	0	-0.32	9	9
BCL2/BAX	0.034	0.032	-10000	0	-0.29	4	4
CaM/Ca2+/Calcineurin A alpha-beta B1	0.02	0.008	-10000	0	-10000	0	0
CaM/Ca2+	0.02	0.008	-10000	0	-10000	0	0
BAX	0.027	0.004	-10000	0	-10000	0	0
MAPK14	0.027	0.006	-10000	0	-10000	0	0
BAD	0.027	0.005	-10000	0	-10000	0	0
CABIN1/MEF2D	0.01	0.079	0.23	2	-0.28	14	16
Calcineurin A alpha-beta B1/BCL2	0.022	0.039	-10000	0	-0.4	4	4
FKBP8	0.028	0.004	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.01	0.078	0.28	14	-0.22	2	16
KPNB1	0.028	0.002	-10000	0	-10000	0	0
KPNA2	0.028	0.004	-10000	0	-10000	0	0
XPO1	0.028	0.004	-10000	0	-10000	0	0
SFN	0.024	0.04	-10000	0	-0.42	4	4
MAP3K8	0.024	0.038	-10000	0	-0.46	3	3
NFAT4/CK1 alpha	0.03	0.021	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	0.047	0.095	0.26	1	-0.39	7	8
CABIN1	-0.001	0.078	0.2	6	-0.3	14	20
CALM1	0.026	0.007	-10000	0	-10000	0	0
RAN	0.028	0.003	-10000	0	-10000	0	0
MAP3K1	0.026	0.007	-10000	0	-10000	0	0
CAMK4	0.005	0.092	-10000	0	-0.4	25	25
mol:Ca2+	0	0.002	-10000	0	-10000	0	0
MAPK3	0.028	0.004	-10000	0	-10000	0	0
YWHAH	0.027	0.004	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.024	0.068	-10000	0	-0.27	25	25
YWHAB	0.026	0.007	-10000	0	-10000	0	0
MAPK8	0.022	0.053	-10000	0	-0.46	6	6
MAPK9	0.026	0.007	-10000	0	-10000	0	0
YWHAG	0.027	0.006	-10000	0	-10000	0	0
FKBP1A	0.027	0.006	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.034	0.099	0.26	4	-0.39	5	9
PRKCH	0.026	0.007	-10000	0	-10000	0	0
CABIN1/Cbp/p300	0.038	0.021	-10000	0	-0.33	1	1
CASP3	0.027	0.007	-10000	0	-10000	0	0
PIM1	0.026	0.022	-10000	0	-0.46	1	1
Calcineurin A alpha-beta B1/FKBP12/FK506	0.018	0.006	-10000	0	-10000	0	0
apoptosis	0.018	0.012	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.03	0.04	-10000	0	-0.34	1	1
PRKCB	0.021	0.054	-10000	0	-0.41	8	8
PRKCE	0.027	0.022	-10000	0	-0.46	1	1
JNK2/NFAT4	0.029	0.041	-10000	0	-0.32	1	1
BAD/BCL-XL	0.037	0.013	-10000	0	-10000	0	0
PRKCD	0.024	0.009	-10000	0	-10000	0	0
NUP214	0.027	0.005	-10000	0	-10000	0	0
PRKCZ	0.026	0.022	-10000	0	-0.46	1	1
PRKCA	0.026	0.029	-10000	0	-0.42	2	2
PRKCG	-0.031	0.13	-10000	0	-0.39	58	58
PRKCQ	0.017	0.069	-10000	0	-0.45	11	11
FKBP38/BCL2	0.034	0.031	-10000	0	-0.28	4	4
EP300	0.026	0.023	-10000	0	-0.46	1	1
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.026	0.007	-10000	0	-10000	0	0
NFATc/JNK1	0.035	0.097	0.26	5	-0.36	7	12
CaM/Ca2+/FKBP38	0.035	0.013	-10000	0	-10000	0	0
FKBP12/FK506	0.02	0.005	-10000	0	-10000	0	0
CSNK1A1	0.014	0.007	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0.021	0.058	-10000	0	-0.23	24	24
NFATc/ERK1	0.036	0.095	0.25	6	-0.35	7	13
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	0.014	0.088	-10000	0	-0.32	9	9
NR4A1	0.018	0.1	0.24	6	-0.46	13	19
GSK3B	0.025	0.009	-10000	0	-10000	0	0
positive T cell selection	0.02	0.018	-10000	0	-0.35	1	1
NFAT1/CK1 alpha	0.009	0.06	0.16	1	-0.26	11	12
RCH1/ KPNB1	0.041	0.006	-10000	0	-10000	0	0
YWHAQ	0.028	0.003	-10000	0	-10000	0	0
PRKACA	0.028	0.004	-10000	0	-10000	0	0
AKAP5	0.006	0.089	-10000	0	-0.39	25	25
MEF2D	0.027	0.007	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.024	0.01	-10000	0	-10000	0	0
NFATc/p38 alpha	0.037	0.094	0.25	6	-0.34	7	13
CREBBP	0.027	0.008	-10000	0	-10000	0	0
BCL2	0.022	0.039	-10000	0	-0.41	4	4

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	0.024	0.07	-10000	0	-0.29	23	23
AKT1	0.059	0.091	0.34	9	-0.48	2	11
PTK2B	0.017	0.074	0.53	1	-0.56	2	3
VEGFR2 homodimer/Frs2	0.033	0.044	-10000	0	-0.64	2	2
CAV1	-0.004	0.11	-10000	0	-0.39	38	38
CALM1	0.026	0.007	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.046	0.049	-10000	0	-0.59	2	2
endothelial cell proliferation	0.058	0.11	0.31	32	-0.45	2	34
mol:Ca2+	0.024	0.053	0.36	1	-0.47	3	4
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.056	0.053	-10000	0	-0.56	2	2
RP11-342D11.1	0.012	0.048	-10000	0	-0.47	3	3
CDH5	0.025	0.029	-10000	0	-0.42	2	2
VEGFA homodimer	0.055	0.043	-10000	0	-0.21	6	6
SHC1	0.028	0.004	-10000	0	-10000	0	0
SHC2	0.021	0.052	-10000	0	-0.42	7	7
HRAS/GDP	0.043	0.047	-10000	0	-0.48	2	2
SH2D2A	-0.037	0.15	-10000	0	-0.39	80	80
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.051	0.1	0.31	4	-0.44	6	10
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.008	0.1	-10000	0	-0.53	4	4
VEGFR1 homodimer	0.026	0.019	-10000	0	-0.39	1	1
SHC/GRB2/SOS1	0.072	0.057	-10000	0	-0.52	2	2
GRB10	0.023	0.05	0.36	1	-0.54	2	3
PTPN11	0.028	0.002	-10000	0	-10000	0	0
GRB2	0.027	0.004	-10000	0	-10000	0	0
PAK1	0.025	0.008	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.063	0.061	-10000	0	-0.55	2	2
HRAS	0.026	0.02	-10000	0	-0.4	1	1
VEGF/Rho/ROCK1/Integrin Complex	0.016	0.055	-10000	0	-0.33	5	5
HIF1A	0.025	0.023	-10000	0	-0.46	1	1
FRS2	0.027	0.006	-10000	0	-10000	0	0
oxygen and reactive oxygen species metabolic process	0.054	0.052	-10000	0	-0.56	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.021	0.05	-10000	0	-0.4	7	7
Nck/Pak	0.032	0.018	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.046	0.052	-10000	0	-0.59	2	2
mol:GDP	0.056	0.051	-10000	0	-0.44	3	3
mol:NADP	0.037	0.1	0.32	6	-0.4	9	15
eNOS/Hsp90	0.044	0.096	0.3	3	-0.38	7	10
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
mol:IP3	0.024	0.053	0.37	1	-0.48	3	4
HIF1A/ARNT	0.038	0.02	-10000	0	-0.33	1	1
SHB	0.025	0.009	-10000	0	-10000	0	0
VEGFA	0.023	0.045	-10000	0	-0.38	6	6
VEGFC	-0.033	0.15	-10000	0	-0.39	74	74
FAK1/Vinculin	0.044	0.09	0.44	2	-0.59	2	4
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.025	0.009	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.047	0.075	-10000	0	-0.58	2	2
PTPN6	0.026	0.007	-10000	0	-10000	0	0
EPAS1	0.034	0.024	-10000	0	-0.33	2	2
mol:L-citrulline	0.037	0.1	0.32	6	-0.4	9	15
ITGAV	0.025	0.027	-10000	0	-0.39	2	2
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.058	0.051	-10000	0	-0.56	2	2
VEGFR2 homodimer/VEGFA homodimer	0.05	0.054	-10000	0	-0.51	3	3
VEGFR2/3 heterodimer	0.029	0.053	-10000	0	-0.52	3	3
VEGFB	0.027	0.005	-10000	0	-10000	0	0
MAPK11	0.012	0.057	0.25	8	-0.53	2	10
VEGFR2 homodimer	0.021	0.047	-10000	0	-0.72	2	2
FLT1	0.026	0.019	-10000	0	-0.39	1	1
NEDD4	0.029	0.007	-10000	0	-10000	0	0
MAPK3	0.011	0.063	0.32	3	-0.44	3	6
MAPK1	0.012	0.064	0.3	5	-0.5	2	7
VEGFA145/NRP2	0.035	0.037	-10000	0	-0.27	7	7
VEGFR1/2 heterodimer	0.032	0.045	-10000	0	-0.64	2	2
KDR	0.021	0.047	-10000	0	-0.72	2	2
VEGFA165/NRP1/VEGFR2 homodimer	0.05	0.052	-10000	0	-0.47	3	3
SRC	0.026	0.007	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	0.02	0.07	0.29	7	-0.51	2	9
PI3K	0.032	0.054	-10000	0	-0.51	2	2
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.039	0.051	-10000	0	-0.59	2	2
FES	0.025	0.054	0.37	1	-0.48	3	4
GAB1	0.033	0.058	-10000	0	-0.59	2	2
VEGFR2 homodimer/VEGFA homodimer/Src	0.044	0.052	-10000	0	-0.59	2	2
CTNNB1	0.024	0.009	-10000	0	-10000	0	0
SOS1	0.028	0.004	-10000	0	-10000	0	0
ARNT	0.027	0.004	-10000	0	-10000	0	0
eNOS/Caveolin-1	0.035	0.11	0.32	3	-0.38	7	10
VEGFR2 homodimer/VEGFA homodimer/Yes	0.043	0.047	-10000	0	-0.5	2	2
PI3K/GAB1	0.057	0.083	0.28	4	-0.49	2	6
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.056	0.058	-10000	0	-0.55	2	2
PRKACA	0.028	0.004	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.006	0.1	-10000	0	-0.47	5	5
HSP90AA1	0.026	0.007	-10000	0	-10000	0	0
CDC42	0.025	0.054	0.37	1	-0.48	3	4
actin cytoskeleton reorganization	0.008	0.1	-10000	0	-0.52	4	4
PTK2	0.021	0.064	0.3	1	-0.63	2	3
EDG1	0.012	0.048	-10000	0	-0.47	3	3
mol:DAG	0.024	0.053	0.37	1	-0.48	3	4
CaM/Ca2+	0.037	0.053	-10000	0	-0.44	3	3
MAP2K3	0.009	0.048	-10000	0	-0.45	2	2
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.057	0.064	-10000	0	-0.56	2	2
PLCG1	0.024	0.054	0.37	1	-0.48	3	4
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.051	0.055	-10000	0	-0.55	2	2
IQGAP1	0.027	0.004	-10000	0	-10000	0	0
YES1	0.025	0.009	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.047	0.051	-10000	0	-0.59	2	2
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.045	0.05	-10000	0	-0.59	2	2
cell migration	0.051	0.092	0.34	9	-0.52	2	11
mol:PI-3-4-5-P3	0.031	0.052	-10000	0	-0.47	2	2
FYN	0.027	0.019	-10000	0	-0.39	1	1
VEGFB/NRP1	0.028	0.049	-10000	0	-0.45	3	3
mol:NO	0.037	0.1	0.32	6	-0.4	9	15
PXN	0.028	0.002	-10000	0	-10000	0	0
HRAS/GTP	0.024	0.042	-10000	0	-0.48	2	2
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.039	0.049	-10000	0	-0.56	2	2
VHL	0.025	0.009	-10000	0	-10000	0	0
ITGB3	0.01	0.087	-10000	0	-0.41	21	21
NOS3	0.037	0.11	0.33	6	-0.44	9	15
VEGFR2 homodimer/VEGFA homodimer/Sck	0.043	0.058	-10000	0	-0.52	3	3
RAC1	0.026	0.007	-10000	0	-10000	0	0
PRKCA	0.017	0.057	0.36	1	-0.45	3	4
PRKCB	0.014	0.061	0.36	1	-0.45	3	4
VCL	0.027	0.004	-10000	0	-10000	0	0
VEGFA165/NRP1	0.031	0.051	-10000	0	-0.47	3	3
VEGFR1/2 heterodimer/VEGFA homodimer	0.045	0.052	-10000	0	-0.59	2	2
VEGFA165/NRP2	0.035	0.037	-10000	0	-0.27	7	7
MAPKKK cascade	0.036	0.053	-10000	0	-0.48	2	2
NRP2	0.026	0.026	-10000	0	-0.39	2	2
VEGFC homodimer	-0.033	0.14	-10000	0	-0.39	74	74
NCK1	0.023	0.011	-10000	0	-10000	0	0
ROCK1	0.026	0.007	-10000	0	-10000	0	0
FAK1/Paxillin	0.043	0.092	0.44	2	-0.59	2	4
MAP3K13	0.014	0.047	-10000	0	-0.47	2	2
PDPK1	0.022	0.048	-10000	0	-0.43	2	2

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	-0.003	0.084	-10000	0	-0.34	17	17
KLHL20	0.025	0.07	0.19	9	-0.25	6	15
CYFIP2	0.025	0.029	-10000	0	-0.42	2	2
Rac1/GDP	0.024	0.077	0.33	5	-0.3	1	6
ENAH	-0.008	0.11	-10000	0	-0.35	26	26
AP1M1	0.028	0.004	-10000	0	-10000	0	0
RAP1B	0.027	0.006	-10000	0	-10000	0	0
RAP1A	0.027	0.005	-10000	0	-10000	0	0
CTNNB1	0.025	0.009	-10000	0	-10000	0	0
CDC42/GTP	0.02	0.035	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.011	0.03	-10000	0	-0.17	7	7
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.056	0.044	-10000	0	-0.25	6	6
RAPGEF1	0	0.096	0.29	2	-0.38	5	7
CTNND1	0.028	0.003	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.003	0.11	-10000	0	-0.35	26	26
CRK	0.005	0.095	-10000	0	-0.39	8	8
E-cadherin/gamma catenin/alpha catenin	0.047	0.049	-10000	0	-0.36	6	6
alphaE/beta7 Integrin	0.038	0.025	-10000	0	-0.33	2	2
IQGAP1	0.027	0.004	-10000	0	-10000	0	0
NCKAP1	0.027	0.005	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.049	0.017	-10000	0	-10000	0	0
DLG1	0	0.082	-10000	0	-0.35	13	13
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.002	0.019	-10000	0	-10000	0	0
MLLT4	0.027	0.005	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.045	0.036	-10000	0	-0.25	6	6
PI3K	0.006	0.025	-10000	0	-10000	0	0
ARF6	0.026	0.007	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
E-cadherin/gamma catenin	0.034	0.052	-10000	0	-0.42	6	6
TIAM1	0.021	0.053	-10000	0	-0.46	6	6
E-cadherin(dimer)/Ca2+	0.053	0.039	-10000	0	-0.24	5	5
AKT1	0.012	0.03	0.14	1	-10000	0	1
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
CDH1	0.021	0.053	-10000	0	-0.46	6	6
RhoA/GDP	0.031	0.073	0.33	6	-10000	0	6
actin cytoskeleton organization	0.021	0.054	0.15	15	-0.18	6	21
CDC42/GDP	0.027	0.08	0.33	6	-10000	0	6
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.017	0.036	-10000	0	-0.32	5	5
ITGB7	0.026	0.031	-10000	0	-0.46	2	2
RAC1	0.026	0.007	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.057	0.041	-10000	0	-0.25	5	5
E-cadherin/Ca2+/beta catenin/alpha catenin	0.039	0.035	-10000	0	-0.23	6	6
mol:GDP	0.013	0.085	0.34	6	-0.34	1	7
CDC42/GTP/IQGAP1	0.036	0.008	-10000	0	-10000	0	0
JUP	0.026	0.031	-10000	0	-0.46	2	2
p120 catenin/RhoA/GDP	0.034	0.075	0.34	4	-10000	0	4
RAC1/GTP/IQGAP1	0.035	0.011	-10000	0	-10000	0	0
PIP5K1C/AP1M1	0.04	0.008	-10000	0	-10000	0	0
RHOA	0.025	0.009	-10000	0	-10000	0	0
CDC42	0.027	0.005	-10000	0	-10000	0	0
CTNNA1	0.027	0.006	-10000	0	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.011	0.037	0.12	4	-0.17	6	10
NME1	0.027	0.018	-10000	0	-0.39	1	1
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	-0.006	0.1	-10000	0	-0.35	20	20
regulation of cell-cell adhesion	0.013	0.029	-10000	0	-10000	0	0
WASF2	0.013	0.028	-10000	0	-10000	0	0
Rap1/GTP	0.032	0.055	0.3	5	-10000	0	5
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.068	0.052	-10000	0	-0.47	2	2
CCND1	0.012	0.044	0.14	3	-0.21	6	9
VAV2	0.013	0.12	-10000	0	-0.56	5	5
RAP1/GDP	0.035	0.066	0.33	5	-10000	0	5
adherens junction assembly	-0.005	0.099	-10000	0	-0.34	20	20
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.027	0.005	-10000	0	-10000	0	0
PIP5K1C	0.027	0.005	-10000	0	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.05	0.048	-10000	0	-0.44	2	2
E-cadherin/beta catenin	0.008	0.038	-10000	0	-0.34	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	-0.007	0.1	-10000	0	-0.34	25	25
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
Rac1/GTP	-0.021	0.072	-10000	0	-0.37	12	12
E-cadherin/beta catenin/alpha catenin	0.044	0.041	-10000	0	-0.27	6	6
ITGAE	0.027	0.006	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.003	0.11	-10000	0	-0.36	26	26

×

Class I PI3K signaling events

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
ARF5/GTP	0	0.048	-10000	0	-10000	0	0
DAPP1	0.023	0.1	0.27	13	-0.37	11	24
Src family/SYK family/BLNK-LAT/BTK-ITK	0.01	0.13	0.28	5	-0.47	11	16
mol:DAG	0.016	0.075	0.2	24	-0.22	2	26
HRAS	0.027	0.019	-10000	0	-0.38	1	1
RAP1A	0.028	0.006	-10000	0	-10000	0	0
ARF5/GDP	0.027	0.067	-10000	0	-0.31	6	6
PLCG2	0.025	0.023	-10000	0	-0.46	1	1
PLCG1	0.027	0.006	-10000	0	-10000	0	0
ARF5	0.026	0.007	-10000	0	-10000	0	0
mol:GTP	-0.004	0.039	-10000	0	-10000	0	0
ARF1/GTP	0.007	0.04	0.24	2	-10000	0	2
RHOA	0.025	0.009	-10000	0	-10000	0	0
YES1	0.025	0.009	-10000	0	-10000	0	0
RAP1A/GTP	-0.003	0.041	-10000	0	-10000	0	0
ADAP1	-0.005	0.038	-10000	0	-10000	0	0
ARAP3	-0.004	0.038	-10000	0	-10000	0	0
INPPL1	0.024	0.01	-10000	0	-10000	0	0
PREX1	0.027	0.006	-10000	0	-10000	0	0
ARHGEF6	0.022	0.053	-10000	0	-0.46	6	6
ARHGEF7	0.027	0.006	-10000	0	-10000	0	0
ARF1	0.027	0.004	-10000	0	-10000	0	0
NRAS	0.028	0.007	-10000	0	-10000	0	0
FYN	0.027	0.019	-10000	0	-0.39	1	1
ARF6	0.026	0.007	-10000	0	-10000	0	0
FGR	0.027	0.019	-10000	0	-0.39	1	1
mol:Ca2+	0.011	0.047	0.18	8	-10000	0	8
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.021	0.053	-10000	0	-0.46	6	6
ZAP70	0.007	0.092	-10000	0	-0.4	25	25
mol:IP3	0.011	0.058	0.19	15	-10000	0	15
LYN	0.024	0.02	-10000	0	-0.39	1	1
ARF1/GDP	0.028	0.068	-10000	0	-0.31	6	6
RhoA/GDP	0.039	0.046	0.24	4	-10000	0	4
PDK1/Src/Hsp90	0.049	0.024	-10000	0	-0.28	1	1
BLNK	-0.017	0.14	-10000	0	-0.46	47	47
actin cytoskeleton reorganization	0.023	0.072	0.23	12	-0.4	1	13
SRC	0.026	0.007	-10000	0	-10000	0	0
PLEKHA2	-0.006	0.013	-10000	0	-0.28	1	1
RAC1	0.026	0.007	-10000	0	-10000	0	0
PTEN	0.024	0.013	-10000	0	-10000	0	0
HSP90AA1	0.026	0.007	-10000	0	-10000	0	0
ARF6/GTP	-0.007	0.036	-10000	0	-10000	0	0
RhoA/GTP	-0.004	0.039	-10000	0	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.004	0.1	-10000	0	-0.34	17	17
BLK	-0.035	0.14	-10000	0	-0.4	70	70
PDPK1	0.027	0.022	-10000	0	-0.46	1	1
CYTH1	-0.005	0.038	-10000	0	-10000	0	0
HCK	0.024	0.029	-10000	0	-0.42	2	2
CYTH3	-0.005	0.036	-10000	0	-10000	0	0
CYTH2	-0.006	0.036	-10000	0	-10000	0	0
KRAS	0.027	0.008	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.018	0.044	-10000	0	-0.45	1	1
SGK1	0.019	0.054	-10000	0	-0.48	1	1
INPP5D	0.025	0.031	-10000	0	-0.46	2	2
mol:GDP	0.014	0.066	-10000	0	-0.32	6	6
SOS1	0.028	0.004	-10000	0	-10000	0	0
SYK	0.024	0.038	-10000	0	-0.46	3	3
ARF6/GDP	0.024	0.044	0.22	6	-10000	0	6
mol:PI-3-4-5-P3	-0.005	0.034	-10000	0	-10000	0	0
ARAP3/RAP1A/GTP	-0.003	0.041	-10000	0	-10000	0	0
VAV1	0.02	0.06	-10000	0	-0.45	8	8
mol:PI-3-4-P2	0.012	0.016	-10000	0	-0.33	1	1
RAS family/GTP/PI3K Class I	0.043	0.034	-10000	0	-10000	0	0
PLEKHA1	-0.006	0.012	-10000	0	-0.28	1	1
Rac1/GDP	0.026	0.065	-10000	0	-0.31	6	6
LAT	0.017	0.065	-10000	0	-0.39	13	13
Rac1/GTP	0.019	0.064	0.19	1	-0.29	9	10
ITK	-0.011	0.046	-10000	0	-10000	0	0
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.015	0.093	0.22	23	-0.29	5	28
LCK	0.018	0.063	-10000	0	-0.39	12	12
BTK	-0.005	0.04	-10000	0	-10000	0	0

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.035	0.073	0.22	3	-0.33	3	6
adherens junction organization	0.011	0.094	0.22	1	-0.36	17	18
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.057	0.083	0.27	3	-0.44	2	5
FMN1	0.005	0.1	-10000	0	-0.36	15	15
mol:IP3	0.011	0.044	-10000	0	-0.36	2	2
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.023	0.085	-10000	0	-0.34	13	13
CTNNB1	0.025	0.01	-10000	0	-10000	0	0
AKT1	0.011	0.05	0.19	1	-0.4	2	3
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.001	0.16	-10000	0	-0.66	19	19
CTNND1	0.03	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.018	0.079	-10000	0	-0.33	11	11
VASP	0.019	0.079	-10000	0	-0.34	11	11
ZYX	0.021	0.075	-10000	0	-0.34	10	10
JUB	0.019	0.081	-10000	0	-0.33	13	13
EGFR(dimer)	0.026	0.09	-10000	0	-0.35	13	13
E-cadherin/beta catenin-gamma catenin	0.041	0.046	-10000	0	-0.35	5	5
mol:PI-3-4-5-P3	0.022	0.062	0.21	1	-0.42	2	3
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
PI3K	0.022	0.063	0.22	1	-0.43	2	3
FYN	0.024	0.073	0.23	6	-0.38	2	8
mol:Ca2+	0.011	0.044	-10000	0	-0.35	2	2
JUP	0.027	0.03	-10000	0	-0.45	2	2
PIK3R1	0.027	0.032	-10000	0	-0.46	2	2
mol:DAG	0.011	0.044	-10000	0	-0.36	2	2
CDH1	0.022	0.052	-10000	0	-0.46	6	6
RhoA/GDP	0.062	0.08	0.26	4	-0.43	2	6
establishment of polarity of embryonic epithelium	0.02	0.077	-10000	0	-0.33	11	11
SRC	0.026	0.007	-10000	0	-10000	0	0
RAC1	0.026	0.007	-10000	0	-10000	0	0
RHOA	0.025	0.009	-10000	0	-10000	0	0
EGFR	0.02	0.044	-10000	0	-0.46	4	4
CASR	0.024	0.064	0.22	4	-0.34	2	6
RhoA/GTP	0.048	0.066	-10000	0	-0.32	2	2
AKT2	0.01	0.051	0.19	1	-0.4	2	3
actin cable formation	0.004	0.099	0.25	2	-0.36	14	16
apoptosis	-0.041	0.08	0.34	4	-0.23	9	13
CTNNA1	0.029	0.008	-10000	0	-10000	0	0
mol:GDP	0.037	0.077	-10000	0	-0.47	2	2
PIP5K1A	0.018	0.08	-10000	0	-0.34	11	11
PLCG1	0.011	0.045	-10000	0	-0.36	2	2
Rac1/GTP	0.033	0.085	-10000	0	-0.39	6	6
homophilic cell adhesion	0.002	0.004	-10000	0	-10000	0	0

×

S1P4 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	0.023	0.039	-9999	-0.41	4	4
CDC42/GTP	0.013	0.073	-9999	-0.31	7	7
PLCG1	0.005	0.061	-9999	-0.32	7	7
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.024	0.009	-9999	-10000	0	0
GNAI3	0.027	0.005	-9999	-10000	0	0
G12/G13	0.037	0.018	-9999	-0.27	1	1
cell migration	0.012	0.071	-9999	-0.3	7	7
S1PR5	0.024	0.04	-9999	-0.42	4	4
S1PR4	0.004	0.096	-9999	-0.39	29	29
MAPK3	0.005	0.061	-9999	-0.32	7	7
MAPK1	0.003	0.058	-9999	-0.28	9	9
S1P/S1P5/Gi	0.019	0.051	-9999	-0.28	6	6
GNAI1	0.026	0.022	-9999	-0.46	1	1
CDC42/GDP	0.02	0.004	-9999	-10000	0	0
S1P/S1P5/G12	0.032	0.03	-9999	-0.25	5	5
RHOA	0.012	0.063	-9999	-0.24	1	1
S1P/S1P4/Gi	0.013	0.062	-9999	-0.31	9	9
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	0.012	0.079	-9999	-0.41	17	17
S1P/S1P4/G12/G13	0.034	0.06	-9999	-0.21	28	28
GNA12	0.025	0.02	-9999	-0.39	1	1
GNA13	0.028	0.003	-9999	-10000	0	0
CDC42	0.027	0.005	-9999	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.027	0.005	-10000	0	-10000	0	0
HDAC2	0.027	0.005	-10000	0	-10000	0	0
GNB1/GNG2	0.038	0.061	-10000	0	-0.28	16	16
forebrain development	-0.022	0.14	-10000	0	-0.54	13	13
GNAO1	0.023	0.039	-10000	0	-0.4	4	4
SMO/beta Arrestin2	0.023	0.07	-10000	0	-0.33	18	18
SMO	0.008	0.092	-10000	0	-0.46	19	19
ARRB2	0.026	0.008	-10000	0	-10000	0	0
GLI3/SPOP	0.048	0.08	0.25	5	-0.38	2	7
mol:GTP	0	0.002	-10000	0	-10000	0	0
GSK3B	0.025	0.009	-10000	0	-10000	0	0
GNAI2	0.024	0.01	-10000	0	-10000	0	0
SIN3/HDAC complex	0.065	0.025	-10000	0	-0.21	1	1
GNAI1	0.026	0.022	-10000	0	-0.46	1	1
XPO1	0.024	0.016	-10000	0	-10000	0	0
GLI1/Su(fu)	-0.022	0.15	-10000	0	-0.58	13	13
SAP30	0.026	0.019	-10000	0	-0.39	1	1
mol:GDP	0.008	0.092	-10000	0	-0.46	19	19
MIM/GLI2A	0.017	0.029	-10000	0	-10000	0	0
IFT88	0.026	0.007	-10000	0	-10000	0	0
GNAI3	0.027	0.005	-10000	0	-10000	0	0
GLI2	0.017	0.07	0.19	8	-0.24	3	11
GLI3	0.036	0.08	0.26	5	-0.36	4	9
CSNK1D	0.027	0.004	-10000	0	-10000	0	0
CSNK1E	0.027	0.005	-10000	0	-10000	0	0
SAP18	0.026	0.007	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.026	0.007	-10000	0	-10000	0	0
GNG2	0.026	0.007	-10000	0	-10000	0	0
Gi family/GTP	0.008	0.072	-10000	0	-0.33	10	10
SIN3B	0.028	0.003	-10000	0	-10000	0	0
SIN3A	0.027	0.004	-10000	0	-10000	0	0
GLI3/Su(fu)	0.037	0.083	-10000	0	-0.43	5	5
GLI2/Su(fu)	0.023	0.074	-10000	0	-0.31	4	4
FOXA2	-0.017	0.13	-10000	0	-0.87	3	3
neural tube patterning	-0.022	0.14	-10000	0	-0.54	13	13
SPOP	0.028	0.002	-10000	0	-10000	0	0
Su(fu)/PIAS1	0.022	0.055	-10000	0	-10000	0	0
GNB1	0.027	0.006	-10000	0	-10000	0	0
CSNK1G2	0.027	0.005	-10000	0	-10000	0	0
CSNK1G3	0.026	0.007	-10000	0	-10000	0	0
MTSS1	0.017	0.029	-10000	0	-10000	0	0
embryonic limb morphogenesis	-0.022	0.14	-10000	0	-0.54	13	13
SUFU	0.015	0.039	-10000	0	-10000	0	0
LGALS3	0.025	0.031	-10000	0	-0.46	2	2
catabolic process	0.049	0.097	0.27	3	-0.42	5	8
GLI3A/CBP	0.003	0.08	-10000	0	-0.34	4	4
KIF3A	0.026	0.007	-10000	0	-10000	0	0
GLI1	-0.023	0.14	-10000	0	-0.55	13	13
RAB23	0.025	0.026	-10000	0	-0.39	2	2
CSNK1A1	0.027	0.006	-10000	0	-10000	0	0
IFT172	0.028	0.003	-10000	0	-10000	0	0
RBBP7	0.027	0.004	-10000	0	-10000	0	0
Su(fu)/Galectin3	0.02	0.058	-10000	0	-0.39	1	1
GNAZ	0.012	0.079	-10000	0	-0.42	17	17
RBBP4	0.026	0.022	-10000	0	-0.46	1	1
CSNK1G1	0.028	0.004	-10000	0	-10000	0	0
PIAS1	0.027	0.004	-10000	0	-10000	0	0
PRKACA	0.028	0.004	-10000	0	-10000	0	0
GLI2/SPOP	0.029	0.071	-10000	0	-10000	0	0
STK36	0.024	0.016	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.005	0.073	-10000	0	-0.39	10	10
PTCH1	-0.022	0.16	-10000	0	-0.84	8	8
MIM/GLI1	-0.017	0.14	-10000	0	-0.59	8	8
CREBBP	0.003	0.08	-10000	0	-0.34	4	4
Su(fu)/SIN3/HDAC complex	0.015	0.088	-10000	0	-0.45	11	11

×

Aurora A signaling

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
Aurora A/GADD45A	0.027	0.028	-10000	0	-10000	0	0
BIRC5	0.01	0.084	-10000	0	-0.39	22	22
NFKBIA	0.013	0.041	0.25	13	-10000	0	13
CPEB1	-0.04	0.16	-10000	0	-0.45	69	69
AKT1	0.013	0.041	0.25	13	-10000	0	13
NDEL1	0.027	0.006	-10000	0	-10000	0	0
Aurora A/BRCA1	0.024	0.024	-10000	0	-10000	0	0
NDEL1/TACC3	0.047	0.034	-10000	0	-10000	0	0
GADD45A	0.027	0.019	-10000	0	-0.39	1	1
GSK3B	0.023	0.009	-10000	0	-10000	0	0
PAK1/Aurora A	0.025	0.026	-10000	0	-10000	0	0
MDM2	0.027	0.006	-10000	0	-10000	0	0
JUB	0	0	-10000	0	-10000	0	0
TPX2	0.014	0.004	-10000	0	-10000	0	0
TP53	0.017	0.028	-10000	0	-0.29	3	3
DLG7	0.008	0.016	-10000	0	-10000	0	0
AURKAIP1	0.026	0.019	-10000	0	-0.39	1	1
ARHGEF7	0.027	0.006	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.05	0.035	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.023	0.024	-10000	0	-10000	0	0
AURKA	0.015	0.02	-10000	0	-10000	0	0
AURKB	0.012	0.017	-10000	0	-0.15	3	3
CDC25B	0.011	0.028	-10000	0	-0.23	1	1
G2/M transition checkpoint	0.007	0.017	-10000	0	-10000	0	0
mRNA polyadenylation	-0.01	0.089	-10000	0	-0.25	51	51
Aurora A/CPEB	-0.009	0.089	-10000	0	-0.25	51	51
Aurora A/TACC1/TRAP/chTOG	0.056	0.044	-10000	0	-10000	0	0
BRCA1	0.028	0.003	-10000	0	-10000	0	0
centrosome duplication	0.025	0.026	-10000	0	-10000	0	0
regulation of centrosome cycle	0.045	0.033	-10000	0	-10000	0	0
spindle assembly	0.055	0.043	-10000	0	-10000	0	0
TDRD7	0.027	0.005	-10000	0	-10000	0	0
Aurora A/RasGAP/Survivin	0.05	0.062	-10000	0	-0.3	4	4
CENPA	0.014	0.021	-10000	0	-0.18	4	4
Aurora A/PP2A	0.026	0.026	-10000	0	-10000	0	0
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	0.013	0.027	-10000	0	-10000	0	0
negative regulation of DNA binding	0.017	0.03	-10000	0	-0.29	3	3
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.04	0.009	-10000	0	-10000	0	0
RASA1	0.024	0.031	-10000	0	-0.46	2	2
Ajuba/Aurora A	0.007	0.017	-10000	0	-10000	0	0
mitotic prometaphase	0	0.014	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.015	0.02	-10000	0	-10000	0	0
TACC1	0.023	0.032	-10000	0	-0.46	2	2
TACC3	0.025	0.02	-10000	0	-0.39	1	1
Aurora A/Antizyme1	0.051	0.033	-10000	0	-10000	0	0
Aurora A/RasGAP	0.025	0.031	-10000	0	-0.27	2	2
OAZ1	0.027	0.005	-10000	0	-10000	0	0
RAN	0.028	0.003	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	0.026	0.005	-10000	0	-10000	0	0
GIT1	0.028	0.003	-10000	0	-10000	0	0
GIT1/beta-PIX/PAK1	0.05	0.019	-10000	0	-10000	0	0
Importin alpha/Importin beta/TPX2	0.014	0.004	-10000	0	-10000	0	0
PPP2R5D	0.027	0.006	-10000	0	-10000	0	0
Aurora A/TPX2	0.018	0.019	-10000	0	-10000	0	0
PAK1	0.025	0.008	-10000	0	-10000	0	0
CKAP5	0.027	0.006	-10000	0	-10000	0	0

×

Aurora C signaling

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
INCENP	0.027	0.004	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	0.042	0.047	-9999	-0.23	12	12
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	0.012	0.013	-9999	-10000	0	0
AURKB	0.02	0.055	-9999	-0.39	9	9
AURKC	0.021	0.051	-9999	-0.41	7	7

×

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	0.017	0.04	-10000	0	-0.41	4	4
positive regulation of NF-kappaB transcription factor activity	0.018	0.055	-10000	0	-0.28	15	15
MAP2K4	0.043	0.055	0.21	3	-0.41	1	4
IKBKB	0.026	0.008	-10000	0	-10000	0	0
TNFRSF10B	0.026	0.008	-10000	0	-10000	0	0
TNFRSF10A	0.025	0.023	-10000	0	-0.46	1	1
SMPD1	0.009	0.015	-10000	0	-0.18	1	1
IKBKG	0.027	0.006	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.012	0.076	-10000	0	-0.4	17	17
TRAIL/TRAILR2	0.025	0.034	-10000	0	-0.29	4	4
TRAIL/TRAILR3	0.019	0.052	-10000	0	-0.28	13	13
TRAIL/TRAILR1	0.025	0.034	-10000	0	-0.29	4	4
TRAIL/TRAILR4	0.018	0.055	-10000	0	-0.28	15	15
TRAIL/TRAILR1/DAP3/GTP	0.033	0.034	-10000	0	-0.22	4	4
IKK complex	0.021	0.034	-10000	0	-10000	0	0
RIPK1	0.027	0.006	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.02	0.003	-10000	0	-10000	0	0
MAPK3	0.008	0.027	-10000	0	-0.29	4	4
MAP3K1	0.031	0.052	-10000	0	-0.43	1	1
TRAILR4 (trimer)	0.012	0.076	-10000	0	-0.4	17	17
TRADD	0.027	0.006	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.025	0.023	-10000	0	-0.46	1	1
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.021	0.04	-10000	0	-0.36	1	1
CFLAR	0.027	0.005	-10000	0	-10000	0	0
MAPK1	0.008	0.027	-10000	0	-0.29	4	4
TRAIL/TRAILR1/FADD/TRADD/RIP	0.036	0.047	-10000	0	-10000	0	0
mol:ceramide	0.009	0.015	-10000	0	-0.18	1	1
FADD	0.02	0.013	-10000	0	-10000	0	0
MAPK8	0.052	0.065	0.24	6	-0.39	1	7
TRAF2	0.023	0.041	-10000	0	-0.39	5	5
TRAILR3 (trimer)	0.013	0.072	-10000	0	-0.4	15	15
CHUK	0.027	0.005	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	0.026	0.037	-10000	0	-0.24	4	4
DAP3	0.028	0.004	-10000	0	-10000	0	0
CASP10	0.07	0.096	0.34	26	-0.3	1	27
JNK cascade	0.018	0.055	-10000	0	-0.28	15	15
TRAIL (trimer)	0.017	0.04	-10000	0	-0.4	4	4
TNFRSF10C	0.013	0.072	-10000	0	-0.4	15	15
TRAIL/TRAILR1/DAP3/GTP/FADD	0.031	0.039	-10000	0	-0.24	1	1
TRAIL/TRAILR2/FADD	0.026	0.037	-10000	0	-0.24	4	4
cell death	0.009	0.015	-10000	0	-0.18	1	1
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.021	0.04	-10000	0	-0.36	1	1
TRAILR2 (trimer)	0.026	0.008	-10000	0	-10000	0	0
CASP8	0.003	0.074	-10000	0	-0.5	9	9
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.036	0.047	-10000	0	-10000	0	0

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.008	0.043	-10000	0	-10000	0	0
PLK1	0.041	0.12	-10000	0	-0.82	2	2
CDKN1B	0.08	0.097	0.31	8	-0.39	2	10
FOXO3	0.057	0.11	-10000	0	-0.67	4	4
KAT2B	0.013	0.094	-10000	0	-0.46	19	19
FOXO1/SIRT1	0.03	0.042	-10000	0	-10000	0	0
CAT	0.046	0.13	-10000	0	-0.91	3	3
CTNNB1	0.024	0.009	-10000	0	-10000	0	0
AKT1	0.034	0.017	-10000	0	-10000	0	0
FOXO1	0.016	0.044	0.24	1	-10000	0	1
MAPK10	0.025	0.069	0.2	30	-0.23	21	51
mol:GTP	0.002	0	-10000	0	-10000	0	0
FOXO4	0.055	0.066	0.3	6	-0.4	1	7
response to oxidative stress	0.01	0.008	-10000	0	-10000	0	0
FOXO3A/SIRT1	0.056	0.12	-10000	0	-0.77	3	3
XPO1	0.028	0.004	-10000	0	-10000	0	0
EP300	0.027	0.023	-10000	0	-0.46	1	1
BCL2L11	0.035	0.025	-10000	0	-10000	0	0
FOXO1/SKP2	0.025	0.041	-10000	0	-10000	0	0
mol:GDP	0.01	0.008	-10000	0	-10000	0	0
RAN	0.029	0.003	-10000	0	-10000	0	0
GADD45A	0.068	0.11	-10000	0	-0.56	9	9
YWHAQ	0.028	0.003	-10000	0	-10000	0	0
FOXO1/14-3-3 family	0.039	0.098	-10000	0	-0.43	9	9
MST1	0.026	0.045	-10000	0	-0.4	5	5
CSNK1D	0.027	0.004	-10000	0	-10000	0	0
CSNK1E	0.027	0.005	-10000	0	-10000	0	0
FOXO4/14-3-3 family	0.035	0.078	-10000	0	-0.39	6	6
YWHAB	0.026	0.007	-10000	0	-10000	0	0
MAPK8	0.036	0.051	0.2	32	-0.23	5	37
MAPK9	0.036	0.043	0.2	30	-10000	0	30
YWHAG	0.027	0.006	-10000	0	-10000	0	0
YWHAE	0.027	0.006	-10000	0	-10000	0	0
YWHAZ	0.024	0.01	-10000	0	-10000	0	0
SIRT1	0.026	0.024	-10000	0	-0.46	1	1
SOD2	0.07	0.093	-10000	0	-0.56	1	1
RBL2	0.04	0.17	-10000	0	-0.69	19	19
RAL/GDP	0.045	0.015	-10000	0	-10000	0	0
CHUK	0.034	0.015	-10000	0	-10000	0	0
Ran/GTP	0.024	0.003	-10000	0	-10000	0	0
CSNK1G2	0.027	0.005	-10000	0	-10000	0	0
RAL/GTP	0.048	0.015	-10000	0	-10000	0	0
CSNK1G1	0.028	0.004	-10000	0	-10000	0	0
FASLG	-0.016	0.24	-10000	0	-1.3	15	15
SKP2	0.025	0.009	-10000	0	-10000	0	0
USP7	0.028	0.005	-10000	0	-10000	0	0
IKBKB	0.031	0.017	-10000	0	-10000	0	0
CCNB1	0.043	0.11	-10000	0	-0.76	2	2
FOXO1-3a-4/beta catenin	0.086	0.092	0.33	6	-10000	0	6
proteasomal ubiquitin-dependent protein catabolic process	0.025	0.04	-10000	0	-10000	0	0
CSNK1A1	0.027	0.006	-10000	0	-10000	0	0
SGK1	0.032	0.026	-10000	0	-0.46	1	1
CSNK1G3	0.026	0.007	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.042	0.008	-10000	0	-10000	0	0
ZFAND5	0.052	0.066	0.37	3	-10000	0	3
SFN	0.024	0.04	-10000	0	-0.42	4	4
CDK2	0.028	0.006	-10000	0	-10000	0	0
FOXO3A/14-3-3	0.037	0.083	-10000	0	-0.38	7	7
CREBBP	0.028	0.007	-10000	0	-10000	0	0
FBXO32	0.07	0.16	0.45	2	-1.1	3	5
BCL6	0.054	0.094	-10000	0	-10000	0	0
RALB	0.028	0.004	-10000	0	-10000	0	0
RALA	0.027	0.007	-10000	0	-10000	0	0
YWHAH	0.027	0.004	-10000	0	-10000	0	0

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.043	0.05	-9999	-0.36	6	6
E-cadherin/beta catenin	0.031	0.041	-9999	-0.32	6	6
CTNNB1	0.024	0.009	-9999	-10000	0	0
JUP	0.026	0.031	-9999	-0.46	2	2
CDH1	0.021	0.053	-9999	-0.46	6	6

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.028	0.01	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.06	0.083	0.24	20	-0.35	4	24
ERC1	0.026	0.008	-10000	0	-10000	0	0
RIP2/NOD2	0.031	0.037	-10000	0	-0.31	5	5
NFKBIA	0.023	0.042	-10000	0	-10000	0	0
BIRC2	0.024	0.01	-10000	0	-10000	0	0
IKBKB	0.026	0.008	-10000	0	-10000	0	0
RIPK2	0.025	0.009	-10000	0	-10000	0	0
IKBKG	0.024	0.028	-10000	0	-10000	0	0
IKK complex/A20	0.047	0.095	-10000	0	-0.4	9	9
NEMO/A20/RIP2	0.025	0.009	-10000	0	-10000	0	0
XPO1	0.028	0.004	-10000	0	-10000	0	0
NEMO/ATM	0.042	0.088	0.26	1	-0.41	10	11
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.028	0.003	-10000	0	-10000	0	0
Exportin 1/RanGTP	0.037	0.007	-10000	0	-10000	0	0
IKK complex/ELKS	0.043	0.081	-10000	0	-0.39	9	9
BCL10/MALT1/TRAF6	0.049	0.02	-10000	0	-10000	0	0
NOD2	0.022	0.046	-10000	0	-0.43	5	5
NFKB1	0.029	0.009	-10000	0	-10000	0	0
RELA	0.028	0.01	-10000	0	-10000	0	0
MALT1	0.025	0.009	-10000	0	-10000	0	0
cIAP1/UbcH5C	0.035	0.015	-10000	0	-10000	0	0
ATM	0.025	0.008	-10000	0	-10000	0	0
TNF/TNFR1A	0.023	0.067	-10000	0	-0.28	23	23
TRAF6	0.027	0.006	-10000	0	-10000	0	0
PRKCA	0.026	0.029	-10000	0	-0.42	2	2
CHUK	0.027	0.005	-10000	0	-10000	0	0
UBE2D3	0.027	0.005	-10000	0	-10000	0	0
TNF	0.008	0.088	-10000	0	-0.4	23	23
NF kappa B1 p50/RelA	0.057	0.029	-10000	0	-0.37	1	1
BCL10	0.027	0.004	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.023	0.042	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.028	0.01	-10000	0	-10000	0	0
TNFRSF1A	0.026	0.007	-10000	0	-10000	0	0
IKK complex	0.052	0.092	0.27	1	-0.41	10	11
CYLD	0.027	0.006	-10000	0	-10000	0	0
IKK complex/PKC alpha	0.059	0.095	-10000	0	-0.4	10	10

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.01	0.077	-10000	0	-10000	0	0
regulation of axonogenesis	-0.005	0.026	0.23	1	-10000	0	1
myoblast fusion	-0.017	0.06	0.3	3	-10000	0	3
mol:GTP	0.011	0.04	-10000	0	-0.16	4	4
regulation of calcium-dependent cell-cell adhesion	-0.041	0.057	0.25	7	-10000	0	7
ARF1/GTP	0.028	0.038	-10000	0	-10000	0	0
mol:GM1	0.004	0.028	-10000	0	-10000	0	0
mol:Choline	0.002	0.03	-10000	0	-0.28	3	3
lamellipodium assembly	0	0.062	-10000	0	-0.35	6	6
MAPK3	0.013	0.046	-10000	0	-0.2	1	1
ARF6/GTP/NME1/Tiam1	0.042	0.058	-10000	0	-0.25	7	7
ARF1	0.027	0.004	-10000	0	-10000	0	0
ARF6/GDP	0.017	0.061	-10000	0	-0.3	3	3
ARF1/GDP	0.02	0.066	-10000	0	-0.28	3	3
ARF6	0.026	0.031	-10000	0	-10000	0	0
RAB11A	0.027	0.004	-10000	0	-10000	0	0
TIAM1	0.021	0.054	-10000	0	-0.46	6	6
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.014	0.045	-10000	0	-10000	0	0
actin filament bundle formation	-0.017	0.063	0.27	3	-10000	0	3
KALRN	-0.008	0.072	-10000	0	-0.25	32	32
RAB11FIP3/RAB11A	0.04	0.008	-10000	0	-10000	0	0
RhoA/GDP	0.017	0.063	-10000	0	-0.28	3	3
NME1	0.026	0.021	-10000	0	-0.39	1	1
Rac1/GDP	0.019	0.064	-10000	0	-0.26	5	5
substrate adhesion-dependent cell spreading	0.011	0.04	-10000	0	-0.16	4	4
cortical actin cytoskeleton organization	0	0.062	-10000	0	-0.36	6	6
RAC1	0.026	0.007	-10000	0	-10000	0	0
liver development	0.011	0.04	-10000	0	-0.16	4	4
ARF6/GTP	0.011	0.04	-10000	0	-0.16	4	4
RhoA/GTP	0.025	0.036	-10000	0	-10000	0	0
mol:GDP	0	0.052	-10000	0	-0.3	3	3
ARF6/GTP/RAB11FIP3/RAB11A	0.042	0.039	-10000	0	-10000	0	0
RHOA	0.025	0.009	-10000	0	-10000	0	0
PLD1	0.006	0.037	-10000	0	-0.32	3	3
RAB11FIP3	0.028	0.004	-10000	0	-10000	0	0
tube morphogenesis	0	0.062	-10000	0	-0.35	6	6
ruffle organization	0.005	0.026	-10000	0	-0.23	1	1
regulation of epithelial cell migration	0.011	0.04	-10000	0	-0.16	4	4
PLD2	0.013	0.031	-10000	0	-10000	0	0
PIP5K1A	0.005	0.026	-10000	0	-0.23	1	1
mol:Phosphatidic acid	0.002	0.03	-10000	0	-0.28	3	3
Rac1/GTP	0	0.062	-10000	0	-0.36	6	6

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.051	0.14	0.26	3	-0.37	19	22
CaM/Ca2+	0.019	0.005	-10000	0	-10000	0	0
AKT1	0.026	0.007	-10000	0	-10000	0	0
AKT2	0.027	0.005	-10000	0	-10000	0	0
STXBP4	0.028	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	-0.063	0.14	0.31	4	-0.38	25	29
YWHAZ	0.024	0.01	-10000	0	-10000	0	0
CALM1	0.026	0.007	-10000	0	-10000	0	0
YWHAQ	0.028	0.003	-10000	0	-10000	0	0
TBC1D4	0.013	0.005	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.027	0.004	-10000	0	-10000	0	0
YWHAB	0.026	0.007	-10000	0	-10000	0	0
SNARE/Synip	0.053	0.014	-10000	0	-10000	0	0
YWHAG	0.027	0.006	-10000	0	-10000	0	0
ASIP	0.005	0.056	-10000	0	-0.39	9	9
PRKCI	0.02	0.013	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0.019	0.005	-10000	0	-10000	0	0
RHOQ	0.028	0.004	-10000	0	-10000	0	0
GYS1	0.012	0.012	0.25	1	-10000	0	1
PRKCZ	0.026	0.022	-10000	0	-0.46	1	1
TRIP10	0.027	0.004	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.037	0.008	-10000	0	-10000	0	0
AS160/14-3-3	0.031	0.042	-10000	0	-0.3	1	1
VAMP2	0.027	0.006	-10000	0	-10000	0	0
SLC2A4	-0.07	0.15	0.32	4	-0.42	25	29
STX4	0.028	0.004	-10000	0	-10000	0	0
GSK3B	0.019	0.009	-10000	0	-10000	0	0
SFN	0.024	0.04	-10000	0	-0.42	4	4
LNPEP	0.024	0.031	-10000	0	-0.46	2	2
YWHAE	0.027	0.006	-10000	0	-10000	0	0

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	-0.023	0.059	0.26	4	-10000	0	4
GNAI2	0.024	0.009	-10000	0	-10000	0	0
S1P/S1P5/G12	0.032	0.03	-10000	0	-0.25	5	5
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.023	0.039	-10000	0	-0.41	4	4
RhoA/GTP	0.024	0.061	-10000	0	-0.26	4	4
negative regulation of cAMP metabolic process	0.019	0.05	-10000	0	-0.27	6	6
GNAZ	0.012	0.079	-10000	0	-0.41	17	17
GNAI3	0.027	0.005	-10000	0	-10000	0	0
GNA12	0.025	0.02	-10000	0	-0.39	1	1
S1PR5	0.024	0.04	-10000	0	-0.42	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	0.019	0.051	-10000	0	-0.28	6	6
RhoA/GDP	0.018	0.007	-10000	0	-10000	0	0
RHOA	0.025	0.009	-10000	0	-10000	0	0
GNAI1	0.026	0.022	-10000	0	-0.46	1	1

×

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.025	0.008	-10000	0	-10000	0	0
SMAD2	0.003	0.05	0.25	2	-0.27	4	6
SMAD3	0.026	0.028	-10000	0	-10000	0	0
SMAD3/SMAD4	0.026	0.088	-10000	0	-0.44	15	15
SMAD4/Ubc9/PIASy	0.049	0.02	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.047	0.058	0.24	1	-10000	0	1
PPM1A	0.026	0.007	-10000	0	-10000	0	0
CALM1	0.026	0.007	-10000	0	-10000	0	0
SMAD2/SMAD4	0.015	0.048	0.24	1	-0.25	4	5
MAP3K1	0.026	0.007	-10000	0	-10000	0	0
TRAP-1/SMAD4	0.025	0.067	-10000	0	-0.33	17	17
MAPK3	0.028	0.004	-10000	0	-10000	0	0
MAPK1	0.027	0.005	-10000	0	-10000	0	0
NUP214	0.027	0.005	-10000	0	-10000	0	0
CTDSP1	0.027	0.006	-10000	0	-10000	0	0
CTDSP2	0.028	0.004	-10000	0	-10000	0	0
CTDSPL	0.024	0.009	-10000	0	-10000	0	0
KPNB1	0.028	0.002	-10000	0	-10000	0	0
TGFBRAP1	0.012	0.088	-10000	0	-0.46	17	17
UBE2I	0.028	0.004	-10000	0	-10000	0	0
NUP153	0.027	0.006	-10000	0	-10000	0	0
KPNA2	0.028	0.004	-10000	0	-10000	0	0
PIAS4	0.027	0.005	-10000	0	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.026	0.019	-9999	-0.39	1	1
Rac1/GDP	0.025	0.011	-9999	-10000	0	0
DOCK1	0.027	0.022	-9999	-0.46	1	1
ITGA4	0.021	0.051	-9999	-0.39	8	8
RAC1	0.026	0.007	-9999	-10000	0	0
alpha4/beta7 Integrin	0.034	0.046	-9999	-0.28	10	10
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.027	0.006	-9999	-10000	0	0
alpha4/beta1 Integrin	0.048	0.038	-9999	-0.23	8	8
alpha4/beta7 Integrin/Paxillin	0.04	0.038	-9999	-0.26	2	2
lamellipodium assembly	0.012	0.062	-9999	-0.37	4	4
PIK3CA	0.02	0.013	-9999	-10000	0	0
PI3K	0.027	0.03	-9999	-0.33	2	2
ARF6	0.026	0.007	-9999	-10000	0	0
TLN1	0.024	0.01	-9999	-10000	0	0
PXN	0.015	0.002	-9999	-10000	0	0
PIK3R1	0.025	0.031	-9999	-0.46	2	2
ARF6/GTP	0.05	0.036	-9999	-10000	0	0
cell adhesion	0.047	0.036	-9999	-10000	0	0
CRKL/CBL	0.035	0.02	-9999	-0.27	1	1
alpha4/beta1 Integrin/Paxillin	0.04	0.034	-9999	-10000	0	0
ITGB1	0.027	0.005	-9999	-10000	0	0
ITGB7	0.026	0.031	-9999	-0.46	2	2
ARF6/GDP	0.025	0.01	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.029	0.085	-9999	-0.27	10	10
p130Cas/Crk/Dock1	0.051	0.022	-9999	-0.28	1	1
VCAM1	-0.015	0.13	-9999	-0.4	51	51
alpha4/beta1 Integrin/Paxillin/Talin	0.048	0.037	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.054	0.036	-9999	-10000	0	0
BCAR1	0.027	0.006	-9999	-10000	0	0
mol:GDP	-0.052	0.036	-9999	-10000	0	0
CBL	0.025	0.008	-9999	-10000	0	0
PRKACA	0.028	0.004	-9999	-10000	0	0
GIT1	0.028	0.003	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.048	0.037	-9999	-10000	0	0
Rac1/GTP	0.012	0.066	-9999	-0.4	4	4

×

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.037	0.02	-10000	0	-0.33	1	1
FBXW11	0.027	0.006	-10000	0	-10000	0	0
NF kappa B1 p50/c-Rel	0.024	0.039	-10000	0	-0.27	8	8
NF kappa B1 p50/RelA/I kappa B alpha	0.032	0.048	0.22	3	-0.28	1	4
NFKBIA	0.016	0.034	-10000	0	-0.31	1	1
MAPK14	0.027	0.006	-10000	0	-10000	0	0
NF kappa B1 p105/p50	0.027	0.011	-10000	0	-10000	0	0
ARRB2	0.015	0.004	-10000	0	-10000	0	0
REL	0.019	0.064	-10000	0	-0.46	9	9
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	0.027	0.017	-10000	0	-0.28	1	1
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	0.027	0.012	-10000	0	-10000	0	0
PIK3CA	0.02	0.013	-10000	0	-10000	0	0
NF kappa B1 p50 dimer	0.02	0.007	-10000	0	-10000	0	0
PIK3R1	0.025	0.031	-10000	0	-0.46	2	2
NFKB1	0.013	0.005	-10000	0	-10000	0	0
RELA	0.027	0.006	-10000	0	-10000	0	0
positive regulation of anti-apoptosis	0.019	0.033	-10000	0	-0.27	1	1
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.033	0.051	0.27	1	-0.27	2	3
SRC	0.026	0.007	-10000	0	-10000	0	0
PI3K	0.027	0.03	-10000	0	-0.33	2	2
NF kappa B1 p50/RelA	0.019	0.033	-10000	0	-0.28	1	1
IKBKB	0.026	0.008	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.026	0.006	-10000	0	-10000	0	0
SYK	0.024	0.038	-10000	0	-0.46	3	3
I kappa B alpha/PIK3R1	0.03	0.054	0.22	6	-0.26	3	9
cell death	0.032	0.049	0.26	1	-0.26	2	3
NF kappa B1 p105/c-Rel	0.024	0.039	-10000	0	-0.27	8	8
LCK	0.018	0.063	-10000	0	-0.39	12	12
BCL3	0.026	0.022	-10000	0	-0.46	1	1

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.06	0.027	-9999	-10000	0	0
HDAC3	0.027	0.006	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0.007	0.002	-9999	-10000	0	0
GATA1/HDAC4	0.037	0.017	-9999	-0.27	1	1
GATA1/HDAC5	0.038	0.016	-9999	-0.27	1	1
GATA2/HDAC5	0.035	0.026	-9999	-0.3	2	2
HDAC5/BCL6/BCoR	0.04	0.027	-9999	-10000	0	0
HDAC9	0.012	0.074	-9999	-0.39	17	17
Glucocorticoid receptor/Hsp90/HDAC6	0.05	0.019	-9999	-10000	0	0
HDAC4/ANKRA2	0.038	0.012	-9999	-10000	0	0
HDAC5/YWHAB	0.039	0.011	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.015	0.005	-9999	-10000	0	0
GATA2	0.023	0.03	-9999	-0.42	2	2
HDAC4/RFXANK	0.039	0.017	-9999	-0.27	1	1
BCOR	0.027	0.022	-9999	-0.46	1	1
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.027	0.005	-9999	-10000	0	0
HDAC5	0.028	0.003	-9999	-10000	0	0
GNB1/GNG2	0.038	0.012	-9999	-10000	0	0
Histones	0.026	0.037	-9999	-10000	0	0
ADRBK1	0.026	0.008	-9999	-10000	0	0
HDAC4	0.027	0.006	-9999	-10000	0	0
XPO1	0.028	0.004	-9999	-10000	0	0
HDAC5/ANKRA2	0.039	0.01	-9999	-10000	0	0
HDAC4/Ubc9	0.039	0.01	-9999	-10000	0	0
HDAC7	0.028	0.003	-9999	-10000	0	0
HDAC5/14-3-3 E	0.039	0.009	-9999	-10000	0	0
TUBA1B	0.028	0.003	-9999	-10000	0	0
HDAC6	0.028	0.004	-9999	-10000	0	0
HDAC5/RFXANK	0.04	0.015	-9999	-0.27	1	1
CAMK4	0.005	0.092	-9999	-0.4	25	25
Tubulin/HDAC6	0.052	0.016	-9999	-10000	0	0
SUMO1	0.027	0.005	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.026	0.007	-9999	-10000	0	0
GATA1	0.018	0.026	-9999	-0.39	1	1
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.027	0.006	-9999	-10000	0	0
NR3C1	0.027	0.006	-9999	-10000	0	0
SUMO1/HDAC4	0.042	0.026	-9999	-10000	0	0
SRF	0.027	0.006	-9999	-10000	0	0
HDAC4/YWHAB	0.038	0.012	-9999	-10000	0	0
Tubulin	0.039	0.01	-9999	-10000	0	0
HDAC4/14-3-3 E	0.038	0.012	-9999	-10000	0	0
GNB1	0.027	0.006	-9999	-10000	0	0
RANGAP1	0.027	0.004	-9999	-10000	0	0
BCL6/BCoR	0.029	0.019	-9999	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0.051	0.017	-9999	-10000	0	0
HDAC4/SRF	0.036	0.063	-9999	-0.24	24	24
HDAC4/ER alpha	0.024	0.072	-9999	-0.3	24	24
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.026	0.037	-9999	-10000	0	0
cell motility	0.052	0.015	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.028	0.004	-9999	-10000	0	0
HDAC7/HDAC3	0.039	0.01	-9999	-10000	0	0
BCL6	0.02	0.013	-9999	-10000	0	0
HDAC4/CaMK II delta B	0.027	0.006	-9999	-10000	0	0
Hsp90/HDAC6	0.038	0.012	-9999	-10000	0	0
ESR1	0.006	0.095	-9999	-0.42	24	24
HDAC6/HDAC11	0.035	0.022	-9999	-0.33	1	1
Ran/GTP/Exportin 1	0.043	0.03	-9999	-10000	0	0
NPC	0.016	0.002	-9999	-10000	0	0
MEF2C	0.017	0.066	-9999	-0.43	11	11
RAN	0.028	0.003	-9999	-10000	0	0
HDAC4/MEF2C	0.067	0.05	-9999	-0.24	5	5
GNG2	0.026	0.007	-9999	-10000	0	0
NCOR2	0.028	0.004	-9999	-10000	0	0
TUBB2A	0.027	0.006	-9999	-10000	0	0
HDAC11	0.024	0.023	-9999	-0.46	1	1
HSP90AA1	0.026	0.007	-9999	-10000	0	0
RANBP2	0.028	0.003	-9999	-10000	0	0
ANKRA2	0.026	0.007	-9999	-10000	0	0
RFXANK	0.027	0.019	-9999	-0.39	1	1
nuclear import	-0.033	0.013	-9999	-10000	0	0

×

PLK2 and PLK4 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
PLK2	0.024	0.031	-9999	-0.46	2	2
PLK4	0.027	0.005	-9999	-10000	0	0
regulation of centriole replication	0.013	0.022	-9999	-0.33	2	2

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	0.048	0.065	-10000	0	-0.29	3	3
Ran/GTP/Exportin 1/HDAC1	0.007	0.002	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.032	0.068	-10000	0	-0.29	1	1
SUMO1	0.027	0.005	-10000	0	-10000	0	0
ZFPM1	0.027	0.006	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.015	0.005	-10000	0	-10000	0	0
FKBP3	0.027	0.006	-10000	0	-10000	0	0
Histones	0.054	0.059	-10000	0	-10000	0	0
YY1/LSF	0.008	0.077	-10000	0	-0.32	6	6
SMG5	0.028	0.004	-10000	0	-10000	0	0
RAN	0.028	0.003	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	0.018	0.037	-10000	0	-10000	0	0
I kappa B alpha/HDAC1	0.026	0.05	-10000	0	-10000	0	0
SAP18	0.026	0.007	-10000	0	-10000	0	0
RELA	0.022	0.043	0.28	1	-0.26	1	2
HDAC1/Smad7	0.048	0.021	-10000	0	-10000	0	0
RANGAP1	0.027	0.004	-10000	0	-10000	0	0
HDAC3/TR2	0.029	0.05	-10000	0	-10000	0	0
NuRD/MBD3 Complex	0.037	0.024	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.033	0.064	0.24	1	-0.34	2	3
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	0.023	0.03	-10000	0	-0.42	2	2
GATA1	0.018	0.026	-10000	0	-0.39	1	1
Mad/Max	0.036	0.034	-10000	0	-0.33	4	4
NuRD/MBD3 Complex/GATA1/Fog1	0.032	0.052	-10000	0	-0.3	1	1
RBBP7	0.027	0.004	-10000	0	-10000	0	0
NPC	0.016	0.002	-10000	0	-10000	0	0
RBBP4	0.026	0.022	-10000	0	-0.46	1	1
MAX	0.026	0.007	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.027	0.006	-10000	0	-10000	0	0
NFKBIA	0.015	0.03	-10000	0	-10000	0	0
KAT2B	0.007	0.092	-10000	0	-0.46	19	19
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.028	0.014	-10000	0	-10000	0	0
SIN3 complex	0.064	0.025	-10000	0	-0.21	1	1
SMURF1	0.026	0.008	-10000	0	-10000	0	0
CHD3	0.027	0.006	-10000	0	-10000	0	0
SAP30	0.026	0.019	-10000	0	-0.39	1	1
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.027	0.006	-10000	0	-10000	0	0
YY1/HDAC3	0.008	0.068	-10000	0	-0.35	4	4
YY1/HDAC2	0.009	0.077	-10000	0	-0.32	6	6
YY1/HDAC1	0.009	0.076	-10000	0	-0.31	6	6
NuRD/MBD2 Complex (MeCP1)	0.034	0.028	-10000	0	-10000	0	0
PPARG	-0.074	0.15	-10000	0	-0.4	17	17
HDAC8/hEST1B	0.055	0.012	-10000	0	-10000	0	0
UBE2I	0.028	0.004	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.026	0.006	-10000	0	-10000	0	0
TNFRSF1A	0.026	0.007	-10000	0	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.029	0.049	-10000	0	-10000	0	0
MBD3L2	-0.017	0.025	-10000	0	-0.39	2	2
ubiquitin-dependent protein catabolic process	0.047	0.021	-10000	0	-10000	0	0
CREBBP	0.027	0.004	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.031	0.05	-10000	0	-0.3	3	3
HDAC1	0.027	0.005	-10000	0	-10000	0	0
HDAC3	0.016	0.03	-10000	0	-10000	0	0
HDAC2	0.027	0.005	-10000	0	-10000	0	0
YY1	0.008	0.056	-10000	0	-0.27	18	18
HDAC8	0.028	0.002	-10000	0	-10000	0	0
SMAD7	0.026	0.008	-10000	0	-10000	0	0
NCOR2	0.028	0.004	-10000	0	-10000	0	0
MXD1	0.023	0.048	-10000	0	-0.46	5	5
STAT3	0.022	0.015	-10000	0	-0.3	1	1
NFKB1	0.027	0.005	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.028	0.003	-10000	0	-10000	0	0
YY1/LSF/HDAC1	0.023	0.077	-10000	0	-0.3	5	5
YY1/SAP30/HDAC1	0.023	0.077	-10000	0	-0.35	4	4
EP300	0.026	0.022	-10000	0	-0.46	1	1
STAT3 (dimer non-phopshorylated)	0.022	0.015	-10000	0	-0.3	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.015	0.03	-10000	0	-10000	0	0
histone deacetylation	0.03	0.035	-10000	0	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.025	0.034	-10000	0	-10000	0	0
nuclear export	-0.054	0.012	-10000	0	-10000	0	0
PRKACA	0.028	0.004	-10000	0	-10000	0	0
GATAD2B	0.028	0.004	-10000	0	-10000	0	0
GATAD2A	0.028	0.003	-10000	0	-10000	0	0
GATA2/HDAC3	0.025	0.05	-10000	0	-0.28	1	1
GATA1/HDAC1	0.038	0.016	-10000	0	-0.27	1	1
GATA1/HDAC3	0.027	0.05	-10000	0	-10000	0	0
CHD4	0.026	0.007	-10000	0	-10000	0	0
TNF-alpha/TNFR1A	0.023	0.067	-10000	0	-0.28	23	23
SIN3/HDAC complex/Mad/Max	0.031	0.035	-10000	0	-0.27	1	1
NuRD Complex	0.03	0.055	-10000	0	-0.31	4	4
positive regulation of chromatin silencing	0.051	0.057	-10000	0	-10000	0	0
SIN3B	0.028	0.003	-10000	0	-10000	0	0
MTA2	0.027	0.005	-10000	0	-10000	0	0
SIN3A	0.027	0.004	-10000	0	-10000	0	0
XPO1	0.028	0.004	-10000	0	-10000	0	0
SUMO1/HDAC1	0.041	0.029	-10000	0	-10000	0	0
HDAC complex	0.067	0.02	-10000	0	-10000	0	0
GATA1/Fog1	0.037	0.017	-10000	0	-0.27	1	1
FKBP25/HDAC1/HDAC2	0.051	0.017	-10000	0	-10000	0	0
TNF	0.008	0.088	-10000	0	-0.4	23	23
negative regulation of cell growth	0.028	0.039	-10000	0	-0.27	1	1
NuRD/MBD2/PRMT5 Complex	0.034	0.028	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.043	0.03	-10000	0	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.018	0.049	-10000	0	-0.29	3	3
SIN3/HDAC complex/NCoR1	0.026	0.04	-10000	0	-0.45	1	1
TFCP2	0.028	0.003	-10000	0	-10000	0	0
NR2C1	0.028	0.003	-10000	0	-10000	0	0
MBD3	0.027	0.005	-10000	0	-10000	0	0
MBD2	0.026	0.008	-10000	0	-10000	0	0

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.04	0.007	-9999	-10000	0	0
FBXW11	0.027	0.006	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.026	0.006	-9999	-10000	0	0
CHUK	0.027	0.005	-9999	-10000	0	0
NF kappa B2 p100/RelB	0.074	0.034	-9999	-10000	0	0
NFKB1	0.027	0.005	-9999	-10000	0	0
MAP3K14	0.028	0.002	-9999	-10000	0	0
NF kappa B1 p50/RelB	0.037	0.029	-9999	-0.27	4	4
RELB	0.024	0.037	-9999	-0.39	4	4
NFKB2	0.027	0.004	-9999	-10000	0	0
NF kappa B2 p52/RelB	0.034	0.024	-9999	-0.22	4	4
regulation of B cell activation	0.034	0.024	-9999	-0.22	4	4

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.027	0.005	-10000	0	-9999	0
Ran/GTP/Exportin 1/HDAC4	0.007	0.006	-10000	0	-9999	0
MDM2/SUMO1	0.039	0.031	-10000	0	-9999	0
HDAC4	0.027	0.006	-10000	0	-9999	0
Ran/GTP/Exportin 1/HDAC1	0.007	0.007	-10000	0	-9999	0
SUMO1	0.027	0.005	-10000	0	-9999	0
NPC/RanGAP1/SUMO1	0.012	0.012	-10000	0	-9999	0
mol:GTP	0	0	-10000	0	-9999	0
XPO1	0.011	0.008	-10000	0	-9999	0
EntrezGene:23636	0	0	-10000	0	-9999	0
RAN	0.028	0.003	-10000	0	-9999	0
EntrezGene:8021	0	0	-10000	0	-9999	0
RANBP2	0.028	0.003	-10000	0	-9999	0
SUMO1/HDAC4	0.042	0.026	-10000	0	-9999	0
SUMO1/HDAC1	0.041	0.029	-10000	0	-9999	0
RANGAP1	0.027	0.004	-10000	0	-9999	0
MDM2/SUMO1/SUMO1	0.061	0.027	-10000	0	-9999	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.015	0.005	-10000	0	-9999	0
Ran/GTP	0.03	0.027	-10000	0	-9999	0
EntrezGene:23225	0	0	-10000	0	-9999	0
MDM2	0.027	0.006	-10000	0	-9999	0
UBE2I	0.028	0.004	-10000	0	-9999	0
Ran/GTP/Exportin 1	0.031	0.037	0.22	10	-9999	10
NPC	0.016	0.002	-10000	0	-9999	0
PIAS2	0.026	0.008	-10000	0	-9999	0
PIAS1	0.027	0.004	-10000	0	-9999	0
EntrezGene:9972	0	0	-10000	0	-9999	0

×

Arf1 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.012	0.029	0.21	3	-10000	0	3
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.017	0.023	0.14	4	-10000	0	4
AP2	0.029	0.019	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.035	0.013	-10000	0	-10000	0	0
CLTB	0.027	0.006	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.018	0.009	-10000	0	-10000	0	0
CD4	0.025	0.029	-10000	0	-0.42	2	2
CLTA	0.025	0.009	-10000	0	-10000	0	0
mol:GTP	-0.001	0.002	-10000	0	-10000	0	0
ARFGAP1	0.007	0.002	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.008	0.009	-10000	0	-10000	0	0
ARF1/GTP	0.033	0.012	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.011	0.006	-10000	0	-10000	0	0
mol:Choline	0.007	0.009	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.028	0.005	-10000	0	-10000	0	0
DDEF1	0.006	0.009	-10000	0	-10000	0	0
ARF1/GDP	0.006	0.013	-10000	0	-10000	0	0
AP2M1	0.02	0.013	-10000	0	-10000	0	0
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	0.013	0.006	-10000	0	-10000	0	0
Rac/GTP	0.02	0.006	-10000	0	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.038	0.013	-10000	0	-10000	0	0
ARFIP2	0.024	0.012	-10000	0	-10000	0	0
COPA	0.027	0.004	-10000	0	-10000	0	0
RAC1	0.026	0.007	-10000	0	-10000	0	0
ARF1/GTP/coatomer protein complex	0.014	0.044	-10000	0	-0.2	1	1
ARF1/GTP/ARHGAP10	0.019	0.006	-10000	0	-10000	0	0
GGA3	0.028	0.004	-10000	0	-10000	0	0
ARF1/GTP/Membrin	0.026	0.018	-10000	0	-0.22	2	2
AP2A1	0.027	0.004	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.008	0.04	-10000	0	-0.21	11	11
ARF1/GDP/Membrin	0.026	0.021	-10000	0	-0.25	2	2
Arfaptin 2/Rac/GDP	0.034	0.012	-10000	0	-10000	0	0
CYTH2	0.029	0.006	-10000	0	-10000	0	0
ARF1/GTP/GGA3	0.037	0.01	-10000	0	-10000	0	0
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.019	0.005	-10000	0	-10000	0	0
mol:Brefeldin A	0	0	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.017	0.029	-10000	0	-0.24	1	1
PLD2	0.007	0.009	-10000	0	-10000	0	0
ARF-GAP1/v-SNARE	0.007	0.002	-10000	0	-10000	0	0
PIP5K1A	0.008	0.009	-10000	0	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0.022	0.019	-10000	0	-10000	0	0
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.007	0.009	-10000	0	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	0.007	0.002	-10000	0	-10000	0	0
GOSR2	0.013	0.021	-10000	0	-0.31	2	2
USO1	0.011	0.029	-10000	0	-0.31	4	4
GBF1	0.01	0.036	-10000	0	-0.31	6	6
ARF1/GTP/Arfaptin 2	0.038	0.012	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.037	0.033	-10000	0	-0.26	2	2

pid_entity	TCGA.WA.A7H4	TCGA.WA.A7GZ	TCGA.UP.A6WW	TCGA.UF.A7JV
109_MAP3K5	0.034	0.034	0	0.034
47_PPARGC1A	0.028	0.028	0.028	-0.46
105_BMP4	0.028	0.028	0.028	0.028
105_BMP6	0.028	0.028	0	0.028
105_BMP7	0.028	0.028	0.028	0.028
105_BMP2	0.028	0.028	0.028	-0.39
131_RELN/VLDLR	0.072	0.072	0.072	0
30_TGFB1/TGF beta receptor Type II	0.028	0.028	0.03	0.027
84_STAT5B	0.031	0.03	-0.43	0.034
84_STAT5A	0.031	0.03	-0.43	0.034