PARADIGM pathway analysis of mRNASeq expression and copy number data

Pathway.Name	Avg.Num.Perturbations
FOXA2 and FOXA3 transcription factor networks	104
FOXM1 transcription factor network	99
Nephrin/Neph1 signaling in the kidney podocyte	68
E-cadherin signaling events	60
ErbB2/ErbB3 signaling events	50
TCGA08_retinoblastoma	50
Stabilization and expansion of the E-cadherin adherens junction	49
Signaling mediated by p38-alpha and p38-beta	41
Signaling events mediated by the Hedgehog family	40
EGFR-dependent Endothelin signaling events	39

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
FOXA2 and FOXA3 transcription factor networks	0.4015	104	4829	46	-1.2	0.02	1000	-1000	-0.098	-1000
FOXM1 transcription factor network	0.3822	99	5088	51	0.019	0.74	1000	-1000	-0.092	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.2625	68	2338	34	-0.24	0.019	1000	-1000	-0.039	-1000
E-cadherin signaling events	0.2317	60	304	5	-0.21	0.019	1000	-1000	0.003	-1000
ErbB2/ErbB3 signaling events	0.1931	50	3298	65	-0.34	0.03	1000	-1000	-0.058	-1000
TCGA08_retinoblastoma	0.1931	50	406	8	-0.071	0.19	1000	-1000	-0.003	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.1892	49	3645	74	-0.22	0.099	1000	-1000	-0.066	-1000
Signaling mediated by p38-alpha and p38-beta	0.1583	41	1830	44	-0.31	0.019	1000	-1000	-0.034	-1000
Signaling events mediated by the Hedgehog family	0.1544	40	2109	52	-0.25	0.099	1000	-1000	-0.036	-1000
EGFR-dependent Endothelin signaling events	0.1506	39	828	21	-0.21	0.027	1000	-1000	-0.042	-1000
Glypican 2 network	0.1390	36	145	4	0.049	0.094	1000	-1000	0.004	-1000
E-cadherin signaling in the nascent adherens junction	0.1351	35	2711	76	-0.21	0.036	1000	-1000	-0.06	-1000
E-cadherin signaling in keratinocytes	0.1274	33	1421	43	-0.21	0.067	1000	-1000	-0.036	-1000
TCGA08_p53	0.1236	32	228	7	-0.016	0.019	1000	-1000	-0.012	-1000
IL4-mediated signaling events	0.1197	31	2865	91	-1.1	0.55	1000	-1000	-0.1	-1000
Wnt signaling	0.1158	30	216	7	-0.028	0.08	1000	-1000	-0.023	-1000
IL12-mediated signaling events	0.1120	29	2590	87	-0.11	0.24	1000	-1000	-0.087	-1000
TCR signaling in naïve CD8+ T cells	0.1120	29	2748	93	-0.11	0.1	1000	-1000	-0.052	-1000
Aurora B signaling	0.1120	29	1994	67	-0.21	0.21	1000	-1000	-0.045	-1000
Reelin signaling pathway	0.1081	28	1582	56	-0.18	0.043	1000	-1000	-0.04	-1000
IL23-mediated signaling events	0.0965	25	1504	60	-0.083	0.084	1000	-1000	-0.079	-1000
PLK1 signaling events	0.0927	24	2074	85	-0.02	0.14	1000	-1000	-0.03	-1000
amb2 Integrin signaling	0.0772	20	1647	82	-0.16	0.11	1000	-1000	-0.036	-1000
Osteopontin-mediated events	0.0734	19	726	38	-0.081	0.027	1000	-1000	-0.042	-1000
Signaling events regulated by Ret tyrosine kinase	0.0734	19	1629	82	-0.14	0.048	1000	-1000	-0.06	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0734	19	1327	68	-0.12	0.15	1000	-1000	-0.074	-1000
Coregulation of Androgen receptor activity	0.0695	18	1382	76	-0.55	0.19	1000	-1000	-0.024	-1000
Syndecan-1-mediated signaling events	0.0695	18	617	34	-0.17	0.11	1000	-1000	-0.047	-1000
Thromboxane A2 receptor signaling	0.0695	18	1914	105	-0.21	0.049	1000	-1000	-0.049	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0656	17	948	54	-0.11	0.097	1000	-1000	-0.06	-1000
Noncanonical Wnt signaling pathway	0.0656	17	460	26	-0.033	0.08	1000	-1000	-0.04	-1000
Endothelins	0.0656	17	1713	96	-0.41	0.083	1000	-1000	-0.056	-1000
Integrins in angiogenesis	0.0656	17	1454	84	-0.27	0.13	1000	-1000	-0.058	-1000
Calcium signaling in the CD4+ TCR pathway	0.0656	17	551	31	-0.003	0.091	1000	-1000	-0.042	-1000
BMP receptor signaling	0.0618	16	1337	81	-0.21	0.057	1000	-1000	-0.048	-1000
Fc-epsilon receptor I signaling in mast cells	0.0579	15	1544	97	-0.077	0.035	1000	-1000	-0.06	-1000
PDGFR-alpha signaling pathway	0.0579	15	693	44	-0.073	0.02	1000	-1000	-0.043	-1000
Effects of Botulinum toxin	0.0579	15	391	26	-0.003	0.091	1000	-1000	-0.012	-1000
BARD1 signaling events	0.0541	14	843	57	-0.097	0.13	1000	-1000	-0.047	-1000
Arf6 signaling events	0.0541	14	884	62	-0.21	0.044	1000	-1000	-0.032	-1000
Aurora C signaling	0.0541	14	103	7	0	0.1	1000	-1000	-0.013	-1000
S1P1 pathway	0.0541	14	519	36	-0.22	0.023	1000	-1000	-0.035	-1000
S1P4 pathway	0.0541	14	354	25	-0.05	0.036	1000	-1000	-0.027	-1000
LPA4-mediated signaling events	0.0502	13	167	12	-0.13	0.005	1000	-1000	-0.023	-1000
Ephrin A reverse signaling	0.0502	13	96	7	0	0.062	1000	-1000	-0.022	-1000
IL2 signaling events mediated by STAT5	0.0502	13	289	22	-0.025	0.087	1000	-1000	-0.053	-1000
Syndecan-4-mediated signaling events	0.0502	13	935	67	-0.11	0.13	1000	-1000	-0.037	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0502	13	1202	88	-0.16	0.063	1000	-1000	-0.06	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0502	13	429	33	-0.082	0.18	1000	-1000	-0.039	-1000
p75(NTR)-mediated signaling	0.0463	12	1532	125	-0.27	0.091	1000	-1000	-0.081	-1000
S1P5 pathway	0.0463	12	208	17	-0.05	0.034	1000	-1000	-0.018	-1000
IL27-mediated signaling events	0.0463	12	635	51	-0.15	0.17	1000	-1000	-0.052	-1000
Signaling events mediated by PTP1B	0.0425	11	896	76	-0.21	0.051	1000	-1000	-0.04	-1000
Nongenotropic Androgen signaling	0.0425	11	602	52	-0.082	0.031	1000	-1000	-0.035	-1000
Visual signal transduction: Cones	0.0386	10	388	38	-0.061	0.051	1000	-1000	-0.026	-1000
Glypican 1 network	0.0386	10	527	48	-0.086	0.034	1000	-1000	-0.027	-1000
FoxO family signaling	0.0386	10	696	64	-0.4	0.16	1000	-1000	-0.052	-1000
LPA receptor mediated events	0.0386	10	1082	102	-0.1	0.11	1000	-1000	-0.06	-1000
Plasma membrane estrogen receptor signaling	0.0386	10	860	86	-0.14	0.042	1000	-1000	-0.054	-1000
Class IB PI3K non-lipid kinase events	0.0386	10	30	3	-0.003	-1000	1000	-1000	-0.01	-1000
Regulation of Androgen receptor activity	0.0386	10	746	70	-0.64	0.022	1000	-1000	-0.052	-1000
ErbB4 signaling events	0.0347	9	623	69	-0.092	0.048	1000	-1000	-0.049	-1000
PLK2 and PLK4 events	0.0347	9	28	3	-0.006	0.032	1000	-1000	-0.024	-1000
Glucocorticoid receptor regulatory network	0.0347	9	1111	114	-0.14	0.069	1000	-1000	-0.056	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0347	9	511	52	-0.1	0.055	1000	-1000	-0.033	-1000
Ephrin B reverse signaling	0.0347	9	445	48	-0.067	0.071	1000	-1000	-0.036	-1000
Signaling mediated by p38-gamma and p38-delta	0.0347	9	146	15	-0.11	0.018	1000	-1000	-0.03	-1000
Insulin Pathway	0.0347	9	731	74	-0.17	0.058	1000	-1000	-0.055	-1000
Visual signal transduction: Rods	0.0347	9	471	52	-0.061	0.051	1000	-1000	-0.045	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0347	9	721	78	-0.056	0.032	1000	-1000	-0.066	-1000
JNK signaling in the CD4+ TCR pathway	0.0309	8	137	17	-0.016	0.067	1000	-1000	-0.034	-1000
HIF-1-alpha transcription factor network	0.0309	8	675	76	-0.24	0.11	1000	-1000	-0.073	-1000
Syndecan-2-mediated signaling events	0.0309	8	596	69	-0.14	0.063	1000	-1000	-0.026	-1000
Ceramide signaling pathway	0.0309	8	653	76	-0.21	0.086	1000	-1000	-0.035	-1000
HIF-2-alpha transcription factor network	0.0309	8	361	43	-0.12	0.13	1000	-1000	-0.06	-1000
S1P3 pathway	0.0309	8	368	42	-0.052	0.031	1000	-1000	-0.042	-1000
Regulation of nuclear SMAD2/3 signaling	0.0270	7	1042	136	-0.26	0.15	1000	-1000	-0.037	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0270	7	197	28	-0.05	0.078	1000	-1000	-0.023	-1000
Presenilin action in Notch and Wnt signaling	0.0270	7	480	61	-0.033	0.067	1000	-1000	-0.056	-1000
IFN-gamma pathway	0.0270	7	505	68	-0.044	0.067	1000	-1000	-0.055	-1000
Nectin adhesion pathway	0.0270	7	498	63	-0.21	0.042	1000	-1000	-0.053	-1000
ceramide signaling pathway	0.0270	7	369	49	-0.018	0.038	1000	-1000	-0.038	-1000
FAS signaling pathway (CD95)	0.0270	7	342	47	-0.11	0.051	1000	-1000	-0.033	-1000
IL2 signaling events mediated by PI3K	0.0270	7	431	58	-0.037	0.072	1000	-1000	-0.047	-1000
Canonical Wnt signaling pathway	0.0270	7	364	51	-0.033	0.065	1000	-1000	-0.059	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0270	7	911	120	-0.079	0.043	1000	-1000	-0.053	-1000
Caspase cascade in apoptosis	0.0232	6	498	74	-0.13	0.044	1000	-1000	-0.043	-1000
Aurora A signaling	0.0232	6	381	60	-0.024	0.13	1000	-1000	-0.036	-1000
EPHB forward signaling	0.0232	6	530	85	-0.077	0.078	1000	-1000	-0.064	-1000
Regulation of Telomerase	0.0232	6	675	102	-0.22	0.12	1000	-1000	-0.055	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0193	5	483	85	-0.051	0.038	1000	-1000	-0.05	-1000
Hedgehog signaling events mediated by Gli proteins	0.0193	5	359	65	-0.053	0.039	1000	-1000	-0.043	-1000
Insulin-mediated glucose transport	0.0193	5	174	32	-0.17	0.035	1000	-1000	-0.035	-1000
Class I PI3K signaling events mediated by Akt	0.0193	5	400	68	-0.11	0.059	1000	-1000	-0.037	-1000
IL6-mediated signaling events	0.0193	5	441	75	-0.029	0.094	1000	-1000	-0.048	-1000
BCR signaling pathway	0.0193	5	592	99	-0.037	0.06	1000	-1000	-0.062	-1000
Signaling events mediated by PRL	0.0193	5	190	34	-0.094	0.03	1000	-1000	-0.044	-1000
Cellular roles of Anthrax toxin	0.0154	4	194	39	-0.062	0.026	1000	-1000	-0.021	-1000
Arf6 downstream pathway	0.0154	4	214	43	-0.051	0.053	1000	-1000	-0.026	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0154	4	148	37	-0.041	0.061	1000	-1000	-0.034	-1000
IL1-mediated signaling events	0.0154	4	299	62	-0.037	0.075	1000	-1000	-0.053	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0154	4	335	83	-0.039	0.036	1000	-1000	-0.041	-1000
Syndecan-3-mediated signaling events	0.0154	4	159	35	-0.016	0.044	1000	-1000	-0.033	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0154	4	199	45	-0.014	0.05	1000	-1000	-0.046	-1000
Regulation of p38-alpha and p38-beta	0.0154	4	252	54	-0.021	0.062	1000	-1000	-0.05	-1000
TCGA08_rtk_signaling	0.0154	4	108	26	-0.026	0.044	1000	-1000	-0.007	-1000
Arf6 trafficking events	0.0154	4	295	71	-0.22	0.056	1000	-1000	-0.038	-1000
PDGFR-beta signaling pathway	0.0154	4	428	97	-0.077	0.078	1000	-1000	-0.058	-1000
Ras signaling in the CD4+ TCR pathway	0.0154	4	78	17	-0.008	0.03	1000	-1000	-0.036	-1000
mTOR signaling pathway	0.0116	3	198	53	-0.022	0.022	1000	-1000	-0.041	-1000
Signaling events mediated by HDAC Class III	0.0116	3	148	40	-0.09	0.033	1000	-1000	-0.028	-1000
TRAIL signaling pathway	0.0116	3	163	48	-0.02	0.041	1000	-1000	-0.038	-1000
Retinoic acid receptors-mediated signaling	0.0116	3	223	58	-0.022	0.038	1000	-1000	-0.053	-1000
Class I PI3K signaling events	0.0116	3	276	73	-0.023	0.052	1000	-1000	-0.042	-1000
IGF1 pathway	0.0116	3	173	57	-0.026	0.043	1000	-1000	-0.052	-1000
Signaling events mediated by HDAC Class II	0.0077	2	203	75	-0.089	0.045	1000	-1000	-0.036	-1000
Signaling events mediated by HDAC Class I	0.0077	2	224	104	-0.089	0.043	1000	-1000	-0.043	-1000
Rapid glucocorticoid signaling	0.0077	2	56	20	-0.016	0.027	1000	-1000	-0.014	-1000
Canonical NF-kappaB pathway	0.0039	1	50	39	-0.014	0.039	1000	-1000	-0.048	-1000
a4b1 and a4b7 Integrin signaling	0.0039	1	8	5	0.019	0.033	1000	-1000	0.005	-1000
EPO signaling pathway	0.0039	1	102	55	-0.015	0.043	1000	-1000	-0.051	-1000
Paxillin-dependent events mediated by a4b1	0.0039	1	52	36	-0.037	0.038	1000	-1000	-0.039	-1000
Atypical NF-kappaB pathway	0.0039	1	51	31	-0.016	0.042	1000	-1000	-0.033	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0039	1	155	125	-0.024	0.041	1000	-1000	-0.067	-1000
VEGFR1 specific signals	0.0039	1	70	56	-0.016	0.045	1000	-1000	-0.042	-1000
p38 MAPK signaling pathway	0.0039	1	84	44	-0.002	0.04	1000	-1000	-0.029	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	15	23	-0.016	0.037	1000	-1000	-0.037	-1000
Circadian rhythm pathway	0.0000	0	16	22	-0.004	0.037	1000	-1000	-0.041	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	5	27	-0.016	0.035	1000	-1000	-0.042	-1000
Arf1 pathway	0.0000	0	26	54	-0.008	0.039	1000	-1000	-0.022	-1000
Alternative NF-kappaB pathway	0.0000	0	0	13	0	0.048	1000	-1000	0	-1000
Total	NA	1852	99555	7203	-16	-990	131000	-131000	-5.5	-131000

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.88	0.39	-10000	0	-1.1	172	172
PCK1	-1	0.65	-10000	0	-1.5	144	144
HNF4A	-1.1	0.46	-10000	0	-1.3	184	184
KCNJ11	-1.1	0.48	-10000	0	-1.3	204	204
AKT1	-0.39	0.13	-10000	0	-0.46	154	154
response to starvation	0	0.001	-10000	0	-10000	0	0
DLK1	-0.99	0.48	-10000	0	-1.2	191	191
NKX2-1	-0.28	0.17	0.31	2	-0.43	112	114
ACADM	-0.88	0.39	-10000	0	-1.1	172	172
TAT	-0.5	0.25	-10000	0	-0.75	102	102
CEBPB	-0.01	0.047	-10000	0	-0.16	1	1
CEBPA	-0.005	0.047	0.25	1	-10000	0	1
TTR	-0.42	0.26	-10000	0	-0.77	67	67
PKLR	-1.1	0.45	-10000	0	-1.3	210	210
APOA1	-1.1	0.44	-10000	0	-1.3	177	177
CPT1C	-0.88	0.39	-10000	0	-1.1	171	171
ALAS1	-0.36	0.14	-10000	0	-0.77	11	11
TFRC	-0.72	0.4	-10000	0	-1	126	126
FOXF1	-0.078	0.22	0.25	5	-0.55	45	50
NF1	0.02	0.004	-10000	0	-10000	0	0
HNF1A (dimer)	-0.089	0.14	-10000	0	-0.5	17	17
CPT1A	-0.88	0.39	-10000	0	-1.1	172	172
HMGCS1	-0.87	0.39	-10000	0	-1.1	179	179
NR3C1	0.024	0.018	-10000	0	-10000	0	0
CPT1B	-0.89	0.39	-10000	0	-1.1	173	173
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.019	0.004	-10000	0	-10000	0	0
GCK	-0.89	0.4	-10000	0	-1.1	175	175
CREB1	-0.064	0.081	-10000	0	-0.2	34	34
IGFBP1	-0.3	0.11	-10000	0	-0.61	4	4
PDX1	-0.44	0.17	-10000	0	-0.8	27	27
UCP2	-0.88	0.39	-10000	0	-1.1	173	173
ALDOB	-1.2	0.43	-10000	0	-1.3	228	228
AFP	-0.15	0.19	0.29	1	-0.45	49	50
BDH1	-0.91	0.41	-10000	0	-1.1	174	174
HADH	-0.94	0.4	-10000	0	-1.1	195	195
F2	-1.1	0.44	-10000	0	-1.3	184	184
HNF1A	-0.089	0.14	-10000	0	-0.5	17	17
G6PC	-0.52	0.58	-10000	0	-1.4	78	78
SLC2A2	-0.98	0.62	-10000	0	-1.6	125	125
INS	-0.021	0.017	-10000	0	-10000	0	0
FOXA1	-0.04	0.16	0.3	4	-0.36	38	42
FOXA3	-0.23	0.26	-10000	0	-0.54	90	90
FOXA2	-1.1	0.46	-10000	0	-1.2	202	202
ABCC8	-0.94	0.41	-10000	0	-1.2	171	171
ALB	-0.29	0.43	0.3	2	-0.94	66	68

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	0.61	0.44	1	126	-10000	0	126
PLK1	0.32	0.3	0.66	93	-1	1	94
BIRC5	0.33	0.3	0.66	93	-0.71	2	95
HSPA1B	0.62	0.45	1	127	-10000	0	127
MAP2K1	0.17	0.14	0.32	110	-10000	0	110
BRCA2	0.67	0.5	1.1	132	-10000	0	132
FOXM1	0.74	0.59	1.2	134	-10000	0	134
XRCC1	0.61	0.45	1	127	-10000	0	127
FOXM1B/p19	0.26	0.33	0.82	51	-10000	0	51
Cyclin D1/CDK4	0.38	0.41	0.87	95	-10000	0	95
CDC2	0.68	0.51	1.1	135	-10000	0	135
TGFA	0.52	0.41	0.9	121	-0.76	1	122
SKP2	0.65	0.51	1.1	127	-10000	0	127
CCNE1	0.065	0.078	0.3	21	-10000	0	21
CKS1B	0.61	0.44	0.98	134	-10000	0	134
RB1	0.15	0.28	0.68	48	-0.55	3	51
FOXM1C/SP1	0.54	0.4	0.9	125	-10000	0	125
AURKB	0.29	0.33	0.69	77	-0.92	4	81
CENPF	0.68	0.51	1.1	133	-10000	0	133
CDK4	0.063	0.06	-10000	0	-10000	0	0
MYC	0.47	0.4	0.86	116	-10000	0	116
CHEK2	0.17	0.14	0.32	107	-10000	0	107
ONECUT1	0.52	0.41	0.91	117	-10000	0	117
CDKN2A	0.085	0.15	0.24	98	-0.29	8	106
LAMA4	0.62	0.46	1	128	-10000	0	128
FOXM1B/HNF6	0.52	0.42	0.94	112	-10000	0	112
FOS	0.55	0.52	1	119	-1	7	126
SP1	0.019	0.007	-10000	0	-10000	0	0
CDC25B	0.61	0.44	1	126	-10000	0	126
response to radiation	0.13	0.11	0.24	103	-10000	0	103
CENPB	0.61	0.44	1	126	-10000	0	126
CENPA	0.68	0.51	1.1	134	-10000	0	134
NEK2	0.66	0.5	1.1	130	-10000	0	130
HIST1H2BA	0.61	0.45	1	126	-10000	0	126
CCNA2	0.12	0.13	0.31	74	-10000	0	74
EP300	0.019	0.004	-10000	0	-10000	0	0
CCNB1/CDK1	0.65	0.48	1.1	126	-10000	0	126
CCNB2	0.69	0.54	1.2	131	-10000	0	131
CCNB1	0.68	0.53	1.1	131	-10000	0	131
ETV5	0.61	0.45	1	130	-10000	0	130
ESR1	0.61	0.5	1	128	-1	4	132
CCND1	0.55	0.42	0.92	129	-10000	0	129
GSK3A	0.14	0.11	0.27	89	-10000	0	89
Cyclin A-E1/CDK1-2	0.18	0.17	0.39	94	-10000	0	94
CDK2	0.054	0.037	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.16	0.14	0.3	117	-10000	0	117
FOXM1B/Cbp/p300	0.16	0.23	0.66	21	-10000	0	21
GAS1	0.61	0.46	1	127	-10000	0	127
MMP2	0.61	0.47	1	131	-0.84	1	132
RB1/FOXM1C	0.32	0.41	0.88	78	-10000	0	78
CREBBP	0.019	0.003	-10000	0	-10000	0	0

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.16	0.22	0.42	107	-10000	0	107
KIRREL	-0.012	0.076	0.23	11	-0.56	1	12
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.16	0.22	-10000	0	-0.42	107	107
PLCG1	0.018	0.004	-10000	0	-10000	0	0
ARRB2	0.018	0.005	-10000	0	-10000	0	0
WASL	0.018	0.005	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.14	0.2	-10000	0	-0.35	110	110
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.14	0.18	-10000	0	-0.33	110	110
FYN	-0.14	0.19	0.25	5	-0.34	110	115
mol:Ca2+	-0.14	0.2	-10000	0	-0.35	109	109
mol:DAG	-0.14	0.2	-10000	0	-0.36	109	109
NPHS2	-0.095	0.18	-10000	0	-0.58	30	30
mol:IP3	-0.14	0.2	-10000	0	-0.36	109	109
regulation of endocytosis	-0.13	0.18	-10000	0	-0.32	108	108
Nephrin/NEPH1/podocin/Cholesterol	-0.14	0.2	-10000	0	-0.35	113	113
establishment of cell polarity	-0.16	0.22	-10000	0	-0.42	107	107
Nephrin/NEPH1/podocin/NCK1-2	-0.12	0.2	-10000	0	-0.33	113	113
Nephrin/NEPH1/beta Arrestin2	-0.13	0.18	-10000	0	-0.33	108	108
NPHS1	-0.24	0.27	-10000	0	-0.56	107	107
Nephrin/NEPH1/podocin	-0.13	0.19	-10000	0	-0.34	110	110
TJP1	0.019	0.004	-10000	0	-10000	0	0
NCK1	0.019	0.002	-10000	0	-10000	0	0
NCK2	0.019	0.002	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.14	0.2	-10000	0	-0.36	109	109
CD2AP	0.018	0.005	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.14	0.2	-10000	0	-0.35	111	111
GRB2	0.019	0.003	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.14	0.18	0.24	6	-0.32	112	118
cytoskeleton organization	-0.18	0.21	-10000	0	-0.4	109	109
Nephrin/NEPH1	-0.11	0.16	-10000	0	-0.3	105	105
Nephrin/NEPH1/ZO-1	-0.12	0.18	-10000	0	-0.34	102	102

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.12	0.19	-10000	0	-0.35	100	100
E-cadherin/beta catenin	-0.15	0.21	-10000	0	-0.41	101	101
CTNNB1	0.019	0.003	-10000	0	-10000	0	0
JUP	0.019	0.002	-10000	0	-10000	0	0
CDH1	-0.21	0.28	0.25	2	-0.55	101	103

×

ErbB2/ErbB3 signaling events

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
USP8	-0.017	0.01	-10000	0	-10000	0	0
RAS family/GTP	-0.16	0.19	0.26	1	-0.45	39	40
NFATC4	-0.15	0.14	0.26	6	-0.27	101	107
ERBB2IP	0.021	0.01	-10000	0	-10000	0	0
HSP90 (dimer)	0.019	0.004	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.2	0.17	-10000	0	-0.32	150	150
JUN	-0.03	0.094	0.24	12	-10000	0	12
HRAS	0.019	0.004	-10000	0	-10000	0	0
DOCK7	-0.2	0.16	0.26	1	-0.32	140	141
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.22	0.19	-10000	0	-0.35	165	165
AKT1	-0.011	0.008	-10000	0	-10000	0	0
BAD	-0.014	0.006	-10000	0	-10000	0	0
MAPK10	-0.15	0.12	0.18	3	-0.28	74	77
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.22	0.18	-10000	0	-0.35	149	149
RAF1	-0.14	0.19	0.29	9	-0.47	29	38
ErbB2/ErbB3/neuregulin 2	-0.23	0.18	-10000	0	-0.35	165	165
STAT3	0.008	0.078	-10000	0	-0.86	2	2
cell migration	-0.13	0.12	0.23	8	-0.25	64	72
mol:PI-3-4-5-P3	-0.004	0.003	-10000	0	-10000	0	0
cell proliferation	-0.079	0.23	0.48	6	-0.54	12	18
FOS	-0.057	0.19	0.36	13	-0.5	17	30
NRAS	0.02	0.003	-10000	0	-10000	0	0
mol:Ca2+	-0.2	0.17	-10000	0	-0.32	150	150
MAPK3	-0.083	0.22	0.44	6	-0.48	19	25
MAPK1	-0.082	0.21	0.44	6	-0.49	19	25
JAK2	-0.19	0.16	0.26	1	-0.32	137	138
NF2	-0.013	0.019	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.21	0.2	-10000	0	-0.34	159	159
NRG1	-0.058	0.18	0.25	5	-0.55	30	35
GRB2/SOS1	0.028	0.008	-10000	0	-10000	0	0
MAPK8	-0.19	0.15	0.21	1	-0.31	139	140
MAPK9	-0.1	0.094	0.17	6	-0.24	20	26
ERBB2	-0.034	0.069	-10000	0	-0.41	8	8
ERBB3	-0.34	0.28	0.25	1	-0.55	159	160
SHC1	0.019	0.005	-10000	0	-10000	0	0
RAC1	0.018	0.006	-10000	0	-10000	0	0
apoptosis	0.03	0.036	-10000	0	-0.15	6	6
STAT3 (dimer)	0.009	0.077	-10000	0	-0.84	2	2
RNF41	-0.023	0.013	-10000	0	-10000	0	0
FRAP1	-0.009	0.005	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.14	0.11	-10000	0	-0.24	134	134
ErbB2/ErbB2/HSP90 (dimer)	-0.031	0.06	-10000	0	-0.36	8	8
CHRNA1	-0.027	0.19	0.4	14	-0.4	4	18
myelination	-0.15	0.15	0.26	8	-0.27	88	96
PPP3CB	-0.19	0.14	0.25	1	-0.3	145	146
KRAS	0.019	0.005	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.18	0.19	-10000	0	-0.32	119	119
NRG2	-0.016	0.13	-10000	0	-0.55	15	15
mol:GDP	-0.21	0.19	-10000	0	-0.34	159	159
SOS1	0.019	0.004	-10000	0	-10000	0	0
MAP2K2	-0.12	0.19	0.31	10	-0.46	26	36
SRC	0.019	0.004	-10000	0	-10000	0	0
mol:cAMP	-0.003	0.002	-10000	0	-10000	0	0
PTPN11	-0.2	0.16	0.26	1	-0.32	144	145
MAP2K1	-0.12	0.22	0.42	5	-0.5	26	31
heart morphogenesis	-0.2	0.17	-10000	0	-0.32	150	150
RAS family/GDP	-0.17	0.19	-10000	0	-0.47	37	37
GRB2	0.019	0.004	-10000	0	-10000	0	0
PRKACA	-0.011	0.017	-10000	0	-10000	0	0
CHRNE	0.005	0.044	0.16	14	-10000	0	14
HSP90AA1	0.019	0.004	-10000	0	-10000	0	0
activation of caspase activity	0.011	0.008	-10000	0	-10000	0	0
nervous system development	-0.2	0.17	-10000	0	-0.32	150	150
CDC42	0.019	0.004	-10000	0	-10000	0	0

×

TCGA08_retinoblastoma

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
CDKN2B	0.043	0.076	0.26	27	-10000	0	27
CDKN2C	-0.018	0.037	0.26	3	-10000	0	3
CDKN2A	0.19	0.11	0.26	182	-10000	0	182
CCND2	-0.056	0.083	0.12	1	-0.21	34	35
RB1	0.061	0.079	0.21	31	-0.14	1	32
CDK4	-0.061	0.083	0.15	1	-0.21	35	36
CDK6	-0.071	0.087	0.15	1	-0.22	35	36
G1/S progression	-0.053	0.11	0.19	20	-0.22	35	55

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	-0.1	0.13	-10000	0	-0.26	93	93
epithelial cell differentiation	-0.099	0.16	-10000	0	-0.3	96	96
CYFIP2	-0.041	0.18	-10000	0	-0.55	27	27
ENAH	-0.094	0.099	0.24	1	-10000	0	1
EGFR	0.016	0.039	0.25	1	-0.55	1	2
EPHA2	0.018	0.005	-10000	0	-10000	0	0
MYO6	-0.12	0.14	-10000	0	-0.3	96	96
CTNNB1	0.019	0.003	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.005	0.12	-10000	0	-0.35	26	26
AQP5	-0.12	0.15	-10000	0	-0.53	11	11
CTNND1	0.019	0.002	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.12	0.13	-10000	0	-0.29	94	94
regulation of calcium-dependent cell-cell adhesion	-0.13	0.14	-10000	0	-0.3	100	100
EGF	-0.21	0.28	-10000	0	-0.55	101	101
NCKAP1	0.019	0.002	-10000	0	-10000	0	0
AQP3	-0.22	0.23	-10000	0	-0.57	62	62
cortical microtubule organization	-0.099	0.16	-10000	0	-0.3	96	96
GO:0000145	-0.12	0.13	-10000	0	-0.28	94	94
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.098	0.17	-10000	0	-0.31	96	96
MLLT4	0.016	0.036	-10000	0	-0.55	1	1
ARF6/GDP	-0.12	0.11	-10000	0	-0.28	86	86
ARF6	0.018	0.004	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.044	0.016	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.11	0.13	-10000	0	-0.28	88	88
PVRL2	0.018	0.005	-10000	0	-10000	0	0
ZYX	-0.12	0.14	-10000	0	-0.3	92	92
ARF6/GTP	0.046	0.021	-10000	0	-10000	0	0
CDH1	-0.21	0.28	0.25	2	-0.55	101	103
EGFR/EGFR/EGF/EGF	-0.2	0.22	-10000	0	-0.38	136	136
RhoA/GDP	-0.094	0.16	-10000	0	-0.29	96	96
actin cytoskeleton organization	-0.12	0.13	-10000	0	-0.29	95	95
IGF-1R heterotetramer	0.014	0.05	-10000	0	-0.55	2	2
GIT1	0.019	0	-10000	0	-10000	0	0
IGF1R	0.014	0.05	-10000	0	-0.55	2	2
IGF1	0.019	0.075	0.25	8	-0.55	3	11
DIAPH1	-0.077	0.24	-10000	0	-0.66	33	33
Wnt receptor signaling pathway	0.099	0.16	0.3	96	-10000	0	96
RHOA	0.019	0.004	-10000	0	-10000	0	0
RhoA/GTP	-0.12	0.12	-10000	0	-0.28	88	88
CTNNA1	0.019	0.003	-10000	0	-10000	0	0
VCL	-0.12	0.14	-10000	0	-0.3	95	95
EFNA1	0.018	0.004	-10000	0	-10000	0	0
LPP	-0.12	0.13	-10000	0	-0.29	93	93
Ephrin A1/EPHA2	-0.094	0.15	-10000	0	-0.29	89	89
SEC6/SEC8	-0.11	0.12	-10000	0	-0.28	73	73
MGAT3	-0.13	0.14	-10000	0	-0.3	100	100
HGF/MET	-0.1	0.16	-10000	0	-0.3	96	96
HGF	-0.004	0.11	-10000	0	-0.55	10	10
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.1	0.13	-10000	0	-0.27	93	93
actin cable formation	-0.089	0.11	-10000	0	-0.29	20	20
KIAA1543	-0.12	0.14	-10000	0	-0.29	96	96
KIFC3	-0.12	0.14	-10000	0	-0.3	96	96
NCK1	0.019	0.002	-10000	0	-10000	0	0
EXOC3	0.017	0.007	-10000	0	-10000	0	0
ACTN1	-0.12	0.14	-10000	0	-0.3	95	95
NCK1/GIT1	0.029	0.004	-10000	0	-10000	0	0
mol:GDP	-0.099	0.16	-10000	0	-0.3	96	96
EXOC4	0.018	0.005	-10000	0	-10000	0	0
STX4	-0.12	0.14	-10000	0	-0.3	96	96
PIP5K1C	-0.12	0.14	-10000	0	-0.3	94	94
LIMA1	0.019	0.004	-10000	0	-10000	0	0
ABI1	0.018	0.004	-10000	0	-10000	0	0
ROCK1	-0.1	0.12	0.26	1	-10000	0	1
adherens junction assembly	-0.13	0.14	-10000	0	-0.52	6	6
IGF-1R heterotetramer/IGF1	-0.094	0.15	-10000	0	-0.29	85	85
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.024	0.028	-10000	0	-0.41	1	1
MET	0.012	0.061	-10000	0	-0.55	3	3
PLEKHA7	-0.13	0.14	-10000	0	-0.3	96	96
mol:GTP	0.043	0.016	-10000	0	-10000	0	0
establishment of epithelial cell apical/basal polarity	-0.089	0.14	0.3	6	-10000	0	6
cortical actin cytoskeleton stabilization	-0.1	0.13	-10000	0	-0.26	93	93
regulation of cell-cell adhesion	-0.12	0.13	-10000	0	-0.29	95	95
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.1	0.13	-10000	0	-0.27	93	93

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	-0.2	0.44	-10000	0	-1.1	50	50
MKNK1	0.019	0.003	-10000	0	-10000	0	0
MAPK14	-0.035	0.14	-10000	0	-0.31	47	47
ATF2/c-Jun	-0.043	0.11	0.39	1	-0.43	1	2
MAPK11	-0.037	0.14	-10000	0	-0.32	46	46
MITF	-0.055	0.15	-10000	0	-0.37	47	47
MAPKAPK5	-0.049	0.15	0.28	1	-0.36	45	46
KRT8	-0.31	0.27	0.28	1	-0.45	180	181
MAPKAPK3	0.019	0.003	-10000	0	-10000	0	0
MAPKAPK2	0.019	0.003	-10000	0	-10000	0	0
p38alpha-beta/CK2	-0.055	0.19	-10000	0	-0.45	49	49
CEBPB	-0.049	0.15	-10000	0	-0.36	45	45
SLC9A1	-0.051	0.15	-10000	0	-0.37	45	45
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	-0.045	0.15	0.27	2	-0.35	45	47
p38alpha-beta/MNK1	-0.034	0.16	-10000	0	-0.37	47	47
JUN	-0.042	0.11	0.38	1	-0.43	1	2
PPARGC1A	-0.12	0.24	-10000	0	-0.44	78	78
USF1	-0.049	0.14	-10000	0	-0.36	44	44
RAB5/GDP/GDI1	-0.04	0.12	-10000	0	-0.27	45	45
NOS2	-0.055	0.18	-10000	0	-1.1	2	2
DDIT3	-0.051	0.15	0.28	1	-0.36	45	46
RAB5A	0.019	0.004	-10000	0	-10000	0	0
HSPB1	-0.047	0.12	0.26	4	-0.31	41	45
p38alpha-beta/HBP1	-0.033	0.16	-10000	0	-0.37	43	43
CREB1	-0.06	0.16	-10000	0	-0.38	47	47
RAB5/GDP	0.014	0.003	-10000	0	-10000	0	0
EIF4E	-0.069	0.13	0.22	2	-0.34	44	46
RPS6KA4	-0.052	0.15	-10000	0	-0.36	47	47
PLA2G4A	-0.082	0.15	0.22	2	-0.37	50	52
GDI1	-0.051	0.15	-10000	0	-0.36	45	45
TP53	-0.081	0.18	-10000	0	-0.45	47	47
RPS6KA5	-0.052	0.15	-10000	0	-0.36	46	46
ESR1	-0.055	0.18	-10000	0	-0.41	43	43
HBP1	0.018	0.005	-10000	0	-10000	0	0
MEF2C	-0.049	0.15	-10000	0	-0.36	44	44
MEF2A	-0.051	0.15	-10000	0	-0.36	46	46
EIF4EBP1	-0.06	0.16	-10000	0	-0.39	45	45
KRT19	-0.22	0.26	0.26	1	-0.42	137	138
ELK4	-0.051	0.15	-10000	0	-0.36	46	46
ATF6	-0.048	0.15	-10000	0	-0.36	43	43
ATF1	-0.06	0.16	-10000	0	-0.38	47	47
p38alpha-beta/MAPKAPK2	-0.034	0.16	-10000	0	-0.38	44	44
p38alpha-beta/MAPKAPK3	-0.034	0.16	-10000	0	-0.37	47	47

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.041	0.17	0.39	1	-0.57	5	6
IHH	-0.095	0.25	0.24	1	-0.58	51	52
SHH Np/Cholesterol/GAS1	-0.055	0.11	-10000	0	-0.32	37	37
LRPAP1	0.019	0.004	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.055	0.11	0.32	37	-10000	0	37
SMO/beta Arrestin2	-0.079	0.2	0.32	1	-0.42	52	53
SMO	-0.089	0.2	-10000	0	-0.44	52	52
AKT1	-0.037	0.12	-10000	0	-0.49	7	7
ARRB2	0.018	0.005	-10000	0	-10000	0	0
BOC	0.019	0.06	0.25	5	-0.55	2	7
ADRBK1	0.019	0.003	-10000	0	-10000	0	0
heart looping	-0.089	0.2	-10000	0	-0.43	53	53
STIL	-0.063	0.17	0.28	8	-0.36	27	35
DHH N/PTCH2	0.014	0.099	-10000	0	-0.41	12	12
DHH N/PTCH1	-0.049	0.17	0.33	1	-0.33	61	62
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
DHH	-0.003	0.12	0.25	4	-0.55	11	15
PTHLH	-0.071	0.23	0.48	1	-1	5	6
determination of left/right symmetry	-0.089	0.2	-10000	0	-0.43	53	53
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
skeletal system development	-0.07	0.23	0.48	1	-1	5	6
IHH N/Hhip	-0.12	0.24	0.25	8	-0.44	86	94
DHH N/Hhip	-0.06	0.19	-10000	0	-0.42	55	55
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.089	0.2	-10000	0	-0.43	53	53
pancreas development	-0.076	0.23	0.25	14	-0.55	46	60
HHAT	0.019	0.004	-10000	0	-10000	0	0
PI3K	0.028	0.017	-10000	0	-0.17	1	1
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	0.019	0.041	0.25	2	-0.55	1	3
somite specification	-0.089	0.2	-10000	0	-0.43	53	53
SHH Np/Cholesterol/PTCH1	-0.081	0.17	0.32	1	-0.31	78	79
SHH Np/Cholesterol/PTCH2	-0.049	0.12	0.22	2	-0.32	37	39
SHH Np/Cholesterol/Megalin	-0.19	0.18	-10000	0	-0.35	134	134
SHH	-0.069	0.14	-10000	0	-0.41	36	36
catabolic process	-0.047	0.17	0.29	9	-0.34	54	63
SMO/Vitamin D3	-0.1	0.19	0.38	2	-0.39	53	55
SHH Np/Cholesterol/Hhip	-0.1	0.17	0.28	1	-0.36	72	73
LRP2	-0.25	0.27	-10000	0	-0.55	117	117
receptor-mediated endocytosis	-0.21	0.22	0.28	1	-0.53	57	58
SHH Np/Cholesterol/BOC	-0.054	0.11	-10000	0	-0.32	38	38
SHH Np/Cholesterol/CDO	-0.053	0.11	0.16	3	-0.32	36	39
mesenchymal cell differentiation	0.099	0.17	0.35	72	-0.27	1	73
mol:Vitamin D3	-0.085	0.17	0.33	3	-0.32	75	78
IHH N/PTCH2	-0.044	0.17	0.24	9	-0.37	52	61
CDON	0.022	0.03	0.25	4	-10000	0	4
IHH N/PTCH1	-0.042	0.17	0.28	7	-0.35	54	61
Megalin/LRPAP1	-0.17	0.21	-10000	0	-0.4	118	118
PTCH2	0.026	0.058	0.25	10	-0.55	1	11
SHH Np/Cholesterol	-0.053	0.11	-10000	0	-0.32	36	36
PTCH1	-0.047	0.17	0.29	9	-0.34	54	63
HHIP	-0.076	0.23	0.25	14	-0.55	46	60

×

EGFR-dependent Endothelin 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
HRAS	0.019	0.004	-10000	0	-10000	0	0
EGFR	0.016	0.039	0.25	1	-0.55	1	2
EGF/EGFR	-0.1	0.16	-10000	0	-0.3	96	96
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.084	0.17	-10000	0	-0.31	85	85
mol:GTP	0	0	-10000	0	-10000	0	0
EDNRA	0.02	0.015	0.25	1	-10000	0	1
response to oxidative stress	0	0	-10000	0	-10000	0	0
EGF	-0.21	0.28	-10000	0	-0.55	101	101
EGF/EGFR dimer/SHC	-0.11	0.18	-10000	0	-0.35	86	86
mol:GDP	-0.086	0.16	-10000	0	-0.31	85	85
mol:Ca2+	0	0	-10000	0	-10000	0	0
EDN1	0	0.099	-10000	0	-0.55	8	8
GRB2/SOS1	0.027	0.007	-10000	0	-10000	0	0
HRAS/GTP	-0.088	0.15	-10000	0	-0.29	85	85
SHC1	0.018	0.004	-10000	0	-10000	0	0
HRAS/GDP	-0.083	0.16	-10000	0	-0.3	84	84
FRAP1	-0.12	0.13	-10000	0	-0.29	85	85
EGF/EGFR dimer	-0.14	0.21	-10000	0	-0.38	102	102
SOS1	0.019	0.004	-10000	0	-10000	0	0
GRB2	0.019	0.003	-10000	0	-10000	0	0
ETA receptor/Endothelin-1	0.013	0.077	-10000	0	-0.41	8	8

×

Glypican 2 network

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.Total.Perturbations
MDK	0.049	0.079	0.25	33	-9999	33
GPC2	0.09	0.11	0.25	78	-9999	78
GPC2/Midkine	0.094	0.1	0.36	17	-9999	17
neuron projection morphogenesis	0.093	0.1	0.36	17	-9999	17

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	-0.2	0.23	-10000	0	-0.46	105	105
KLHL20	-0.055	0.091	0.17	1	-0.25	4	5
CYFIP2	-0.041	0.18	-10000	0	-0.55	27	27
Rac1/GDP	-0.11	0.14	-10000	0	-0.31	58	58
ENAH	-0.2	0.23	-10000	0	-0.46	106	106
AP1M1	0.019	0.004	-10000	0	-10000	0	0
RAP1B	0.017	0.007	-10000	0	-10000	0	0
RAP1A	0.019	0.003	-10000	0	-10000	0	0
CTNNB1	0.019	0.003	-10000	0	-10000	0	0
CDC42/GTP	-0.095	0.097	-10000	0	-0.26	2	2
ABI1/Sra1/Nap1	-0.063	0.064	-10000	0	-0.19	25	25
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.1	0.18	-10000	0	-0.32	96	96
RAPGEF1	-0.17	0.2	-10000	0	-0.4	97	97
CTNND1	0.019	0.002	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.2	0.24	-10000	0	-0.47	107	107
CRK	-0.18	0.21	-10000	0	-0.43	100	100
E-cadherin/gamma catenin/alpha catenin	-0.12	0.19	-10000	0	-0.35	96	96
alphaE/beta7 Integrin	0.027	0.017	-10000	0	-10000	0	0
IQGAP1	0.019	0.004	-10000	0	-10000	0	0
NCKAP1	0.019	0.002	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.029	0.027	-10000	0	-0.32	1	1
DLG1	-0.2	0.23	-10000	0	-0.46	107	107
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.075	0.071	-10000	0	-0.19	3	3
MLLT4	0.016	0.036	-10000	0	-0.55	1	1
ARF6/GTP/NME1/Tiam1	0.036	0.023	-10000	0	-10000	0	0
PI3K	-0.095	0.091	-10000	0	-0.25	2	2
ARF6	0.018	0.004	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
E-cadherin/gamma catenin	-0.15	0.21	-10000	0	-0.41	100	100
TIAM1	0.024	0.036	0.25	6	-10000	0	6
E-cadherin(dimer)/Ca2+	-0.098	0.17	-10000	0	-0.31	96	96
AKT1	-0.051	0.062	-10000	0	-10000	0	0
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
CDH1	-0.21	0.28	0.25	2	-0.55	101	103
RhoA/GDP	-0.12	0.15	-10000	0	-0.31	65	65
actin cytoskeleton organization	-0.04	0.069	0.14	2	-0.18	4	6
CDC42/GDP	-0.12	0.14	-10000	0	-0.31	63	63
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.1	0.13	-10000	0	-0.27	95	95
ITGB7	0.021	0.021	0.25	2	-10000	0	2
RAC1	0.018	0.006	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.1	0.18	-10000	0	-0.32	96	96
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.1	0.16	-10000	0	-0.3	97	97
mol:GDP	-0.14	0.16	-10000	0	-0.36	66	66
CDC42/GTP/IQGAP1	0.024	0.008	-10000	0	-10000	0	0
JUP	0.019	0.002	-10000	0	-10000	0	0
p120 catenin/RhoA/GDP	-0.11	0.16	-10000	0	-0.32	65	65
RAC1/GTP/IQGAP1	0.023	0.009	-10000	0	-10000	0	0
PIP5K1C/AP1M1	0.027	0.006	-10000	0	-10000	0	0
RHOA	0.019	0.004	-10000	0	-10000	0	0
CDC42	0.019	0.004	-10000	0	-10000	0	0
CTNNA1	0.019	0.003	-10000	0	-10000	0	0
positive regulation of S phase of mitotic cell cycle	-0.026	0.053	0.22	2	-0.25	1	3
NME1	0.019	0.002	-10000	0	-10000	0	0
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	-0.2	0.23	-10000	0	-0.46	102	102
regulation of cell-cell adhesion	-0.084	0.085	-10000	0	-0.22	62	62
WASF2	-0.032	0.041	-10000	0	-0.13	2	2
Rap1/GTP	-0.098	0.12	-10000	0	-0.28	3	3
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.089	0.17	-10000	0	-0.31	91	91
CCND1	-0.033	0.06	0.23	1	-0.31	1	2
VAV2	-0.19	0.23	-10000	0	-0.63	13	13
RAP1/GDP	-0.1	0.13	-10000	0	-0.3	11	11
adherens junction assembly	-0.19	0.22	-10000	0	-0.44	102	102
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.018	0.004	-10000	0	-10000	0	0
PIP5K1C	0.019	0.003	-10000	0	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.095	0.16	-10000	0	-0.3	91	91
E-cadherin/beta catenin	-0.15	0.19	-10000	0	-0.37	108	108
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	-0.2	0.23	-10000	0	-0.45	107	107
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
Rac1/GTP	-0.1	0.13	0.3	1	-0.36	10	11
E-cadherin/beta catenin/alpha catenin	-0.12	0.19	-10000	0	-0.35	97	97
ITGAE	0.018	0.005	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.21	0.24	-10000	0	-0.48	107	107

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	-0.059	0.077	-10000	0	-0.29	3	3
adherens junction organization	-0.11	0.13	-10000	0	-0.28	78	78
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.066	0.076	-10000	0	-0.4	1	1
FMN1	-0.1	0.14	-10000	0	-0.28	77	77
mol:IP3	-0.066	0.076	-10000	0	-0.26	3	3
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.11	0.14	-10000	0	-0.29	87	87
CTNNB1	0.023	0.007	-10000	0	-10000	0	0
AKT1	-0.077	0.089	-10000	0	-0.3	3	3
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.2	0.22	-10000	0	-0.44	103	103
CTNND1	0.017	0.007	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.1	0.13	-10000	0	-0.27	80	80
VASP	-0.11	0.13	-10000	0	-0.28	87	87
ZYX	-0.11	0.13	-10000	0	-0.28	84	84
JUB	-0.11	0.13	-10000	0	-0.27	87	87
EGFR(dimer)	-0.1	0.14	-10000	0	-0.28	82	82
E-cadherin/beta catenin-gamma catenin	-0.11	0.18	-10000	0	-0.34	100	100
mol:PI-3-4-5-P3	-0.066	0.11	-10000	0	-0.31	3	3
PIK3CA	0.007	0.018	-10000	0	-10000	0	0
PI3K	-0.067	0.11	-10000	0	-0.32	3	3
FYN	-0.16	0.13	-10000	0	-0.35	51	51
mol:Ca2+	-0.065	0.075	-10000	0	-0.25	3	3
JUP	0.023	0.007	-10000	0	-10000	0	0
PIK3R1	0.008	0.024	0.25	1	-10000	0	1
mol:DAG	-0.066	0.076	-10000	0	-0.26	3	3
CDH1	-0.21	0.28	0.25	2	-0.55	101	103
RhoA/GDP	-0.066	0.081	-10000	0	-0.4	1	1
establishment of polarity of embryonic epithelium	-0.11	0.13	-10000	0	-0.27	87	87
SRC	0.019	0.004	-10000	0	-10000	0	0
RAC1	0.018	0.006	-10000	0	-10000	0	0
RHOA	0.019	0.004	-10000	0	-10000	0	0
EGFR	0.016	0.039	0.25	1	-0.55	1	2
CASR	-0.19	0.14	-10000	0	-0.33	112	112
RhoA/GTP	-0.053	0.081	-10000	0	-0.24	1	1
AKT2	-0.077	0.088	-10000	0	-0.3	2	2
actin cable formation	-0.1	0.13	-10000	0	-0.27	76	76
apoptosis	0.067	0.09	0.29	4	-0.21	1	5
CTNNA1	0.017	0.007	-10000	0	-10000	0	0
mol:GDP	-0.069	0.079	-10000	0	-0.3	4	4
PIP5K1A	-0.11	0.13	-10000	0	-0.28	80	80
PLCG1	-0.068	0.078	-10000	0	-0.26	3	3
Rac1/GTP	-0.087	0.14	-10000	0	-0.36	6	6
homophilic cell adhesion	-0.002	0.002	-10000	0	-10000	0	0

×

TCGA08_p53

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.Total.Perturbations
CDKN2A	0.1	0.067	0.14	182	-9999	182
TP53	0	0.06	-10000	0	-9999	0
Senescence	0	0.06	-10000	0	-9999	0
Apoptosis	0	0.06	-10000	0	-9999	0
Activated_Oncogenes	0	0	-10000	0	-9999	0
MDM2	-0.016	0.11	0.2	46	-9999	46
MDM4	0.019	0.003	-10000	0	-9999	0

×

IL4-mediated signaling events

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
BCL2L1	-0.5	0.52	0.75	2	-1.2	57	59
STAT6 (cleaved dimer)	-0.48	0.51	-10000	0	-1.1	72	72
IGHG1	-0.16	0.19	0.56	2	-0.98	1	3
IGHG3	-0.48	0.49	0.65	2	-1.1	74	76
AKT1	-0.18	0.27	0.58	5	-0.78	8	13
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.12	0.23	0.56	5	-0.88	5	10
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.2	0.28	0.59	4	-0.96	7	11
THY1	-0.5	0.52	0.75	2	-1.2	61	63
MYB	0.028	0.048	0.25	11	-10000	0	11
HMGA1	0.027	0.044	0.25	9	-10000	0	9
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.23	0.3	0.65	6	-0.64	25	31
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.21	0.28	0.6	4	-0.84	11	15
SP1	0.048	0.053	-10000	0	-10000	0	0
INPP5D	0.021	0.03	0.25	4	-10000	0	4
SOCS5	0.022	0.032	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.47	0.52	0.7	2	-1.1	71	73
SOCS1	-0.31	0.34	0.62	2	-0.74	56	58
SOCS3	-0.19	0.26	0.64	2	-0.86	2	4
FCER2	-0.32	0.39	0.83	3	-0.91	29	32
PARP14	0.022	0.009	-10000	0	-10000	0	0
CCL17	-0.49	0.53	0.92	2	-1.2	60	62
GRB2	0.019	0.003	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.17	0.23	0.56	4	-0.64	10	14
T cell proliferation	-0.48	0.52	0.76	2	-1.2	61	63
IL4R/JAK1	-0.5	0.51	0.66	2	-1.2	63	65
EGR2	-0.5	0.53	0.84	2	-1.2	57	59
JAK2	-0.032	0.051	0.24	1	-10000	0	1
JAK3	0.042	0.069	0.28	19	-10000	0	19
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
JAK1	-0.006	0.029	-10000	0	-10000	0	0
COL1A2	-0.12	0.27	-10000	0	-1.2	8	8
CCL26	-0.5	0.54	0.95	1	-1.3	58	59
IL4R	-0.52	0.55	0.87	2	-1.3	60	62
PTPN6	0.028	0.025	-10000	0	-10000	0	0
IL13RA2	-0.65	0.67	0.84	2	-1.5	86	88
IL13RA1	-0.035	0.049	-10000	0	-10000	0	0
IRF4	-0.049	0.24	0.59	10	-0.7	15	25
ARG1	-0.11	0.18	-10000	0	-1	2	2
CBL	-0.22	0.28	0.61	4	-0.61	25	29
GTF3A	0.061	0.06	-10000	0	-10000	0	0
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.037	0.068	0.27	2	-10000	0	2
IRF4/BCL6	-0.064	0.2	0.46	1	-0.67	15	16
CD40LG	0.052	0.08	0.34	14	-10000	0	14
MAPK14	-0.21	0.28	0.66	3	-0.63	18	21
mitosis	-0.17	0.26	0.55	6	-0.72	8	14
STAT6	-0.56	0.61	1	2	-1.3	72	74
SPI1	0.034	0.056	0.26	15	-10000	0	15
RPS6KB1	-0.17	0.25	0.58	4	-0.7	8	12
STAT6 (dimer)	-0.56	0.61	1	2	-1.3	72	74
STAT6 (dimer)/PARP14	-0.53	0.56	0.71	2	-1.2	73	75
mast cell activation	0.01	0.017	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.18	0.27	0.57	6	-0.88	7	13
FRAP1	-0.18	0.27	0.58	5	-0.78	8	13
LTA	-0.49	0.53	0.92	2	-1.2	56	58
FES	0.019	0.004	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0.55	0.59	1.3	72	-1	2	74
CCL11	-0.7	0.68	-10000	0	-1.4	104	104
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.18	0.26	0.56	6	-0.94	5	11
IL2RG	0.044	0.095	0.28	26	-0.54	2	28
IL10	-0.5	0.52	0.75	2	-1.2	60	62
IRS1	0.019	0.016	0.25	1	-10000	0	1
IRS2	0.017	0.006	-10000	0	-10000	0	0
IL4	-0.11	0.17	0.57	2	-1.2	2	4
IL5	-0.5	0.52	0.74	2	-1.2	59	61
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.41	0.42	0.83	2	-0.94	61	63
COL1A1	-0.12	0.32	0.57	2	-0.97	17	19
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.51	0.52	-10000	0	-1.2	58	58
IL2R gamma/JAK3	0.058	0.1	0.28	33	-0.4	2	35
TFF3	-0.67	0.66	0.74	2	-1.4	90	92
ALOX15	-0.49	0.52	0.75	2	-1.2	59	61
MYBL1	0.031	0.054	0.25	14	-10000	0	14
T-helper 2 cell differentiation	-0.38	0.41	0.78	2	-0.9	61	63
SHC1	0.018	0.004	-10000	0	-10000	0	0
CEBPB	0.02	0.01	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.19	0.26	0.58	4	-0.87	7	11
mol:PI-3-4-5-P3	-0.18	0.27	0.56	6	-0.78	8	14
PI3K	-0.19	0.28	0.62	4	-0.84	8	12
DOK2	0.028	0.046	0.25	10	-10000	0	10
ETS1	0.02	0.032	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.15	0.22	0.53	4	-0.58	8	12
ITGB3	-0.51	0.53	0.75	2	-1.3	59	61
PIGR	-1.1	0.6	0.74	2	-1.4	186	188
IGHE	0.033	0.059	0.17	9	-0.24	1	10
MAPKKK cascade	-0.15	0.21	0.52	4	-0.57	8	12
BCL6	0.013	0.018	-10000	0	-10000	0	0
OPRM1	-0.49	0.52	0.74	2	-1.2	58	60
RETNLB	-0.5	0.51	0.74	2	-1.2	60	62
SELP	-0.71	0.69	0.75	2	-1.4	103	105
AICDA	-0.47	0.5	0.75	1	-1.2	55	56

×

Wnt signaling

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
Noncanonical Wnts/FZD	0.004	0.13	0.25	6	-0.28	27	33
FZD6	0.009	0.071	-10000	0	-0.55	4	4
WNT6	0.024	0.042	0.25	8	-10000	0	8
WNT4	-0.007	0.15	0.25	12	-0.55	16	28
FZD3	-0.028	0.16	0.25	1	-0.55	21	22
WNT5A	0.08	0.1	0.25	66	-10000	0	66
WNT11	0.069	0.097	0.25	55	-10000	0	55

×

IL12-mediated signaling events

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
IL12/IL12R/TYK2/JAK2/SOCS1	0.11	0.18	0.46	47	-10000	0	47
TBX21	0.23	0.38	0.95	46	-10000	0	46
B2M	0.024	0.011	-10000	0	-10000	0	0
TYK2	0.052	0.068	0.23	22	-10000	0	22
IL12RB1	0.072	0.12	0.38	28	-10000	0	28
GADD45B	0.18	0.31	0.78	40	-0.62	1	41
IL12RB2	0.065	0.09	0.26	36	-10000	0	36
GADD45G	0.17	0.34	0.78	41	-0.92	5	46
natural killer cell activation	0.04	0.07	0.15	59	-10000	0	59
RELB	0.018	0.004	-10000	0	-10000	0	0
RELA	0.019	0.003	-10000	0	-10000	0	0
IL18	0.008	0.11	-10000	0	-0.55	9	9
IL2RA	0.052	0.12	0.25	47	-0.55	4	51
IFNG	0.061	0.1	0.25	56	-10000	0	56
STAT3 (dimer)	0.17	0.28	0.68	47	-10000	0	47
HLA-DRB5	-0.001	0.005	-10000	0	-0.023	11	11
FASLG	0.24	0.39	1	43	-10000	0	43
NF kappa B2 p52/RelB	0.052	0.13	-10000	0	-0.54	1	1
CD4	0.022	0.038	0.26	6	-10000	0	6
SOCS1	0.022	0.026	0.25	3	-10000	0	3
EntrezGene:6955	0.005	0.012	0.026	52	-0.026	11	63
CD3D	0.045	0.11	0.27	33	-0.55	3	36
CD3E	0.032	0.12	0.28	26	-0.55	6	32
CD3G	0.081	0.11	0.27	66	-10000	0	66
IL12Rbeta2/JAK2	0.085	0.11	0.34	34	-10000	0	34
CCL3	0.24	0.39	0.96	47	-10000	0	47
CCL4	0.23	0.39	0.97	45	-10000	0	45
HLA-A	0.006	0.01	0.026	51	-10000	0	51
IL18/IL18R	0.064	0.15	0.34	26	-0.36	16	42
NOS2	0.19	0.35	0.88	41	-1.2	1	42
IL12/IL12R/TYK2/JAK2/SPHK2	0.11	0.18	0.46	47	-10000	0	47
IL1R1	0.2	0.36	0.88	41	-1.3	2	43
IL4	-0.052	0.074	-10000	0	-0.23	28	28
JAK2	0.052	0.071	0.24	19	-10000	0	19
EntrezGene:6957	0.005	0.012	0.025	52	-0.022	11	63
TCR/CD3/MHC I/CD8	0.071	0.19	0.41	45	-0.54	5	50
RAB7A	0.16	0.29	0.71	40	-10000	0	40
lysosomal transport	0.16	0.29	0.7	41	-10000	0	41
FOS	0.065	0.46	0.7	36	-1.2	20	56
STAT4 (dimer)	0.18	0.3	0.72	45	-10000	0	45
STAT5A (dimer)	0.18	0.3	0.78	42	-0.54	1	43
GZMA	0.22	0.36	0.92	43	-10000	0	43
GZMB	0.21	0.34	0.84	46	-10000	0	46
HLX	0.022	0.03	0.25	4	-10000	0	4
LCK	0.22	0.36	0.88	49	-0.57	1	50
TCR/CD3/MHC II/CD4	0.038	0.13	0.28	35	-0.36	6	41
IL2/IL2R	0.086	0.13	0.39	25	-0.4	5	30
MAPK14	0.17	0.32	0.76	41	-0.6	4	45
CCR5	0.18	0.36	0.87	41	-0.87	3	44
IL1B	0.04	0.14	0.24	30	-0.56	9	39
STAT6	0.13	0.23	0.55	49	-0.41	4	53
STAT4	0.026	0.041	0.25	8	-10000	0	8
STAT3	0.019	0.001	-10000	0	-10000	0	0
STAT1	0.02	0.015	0.25	1	-10000	0	1
NFKB1	0.019	0.001	-10000	0	-10000	0	0
NFKB2	0.018	0.005	-10000	0	-10000	0	0
IL12B	0.066	0.1	0.3	33	-10000	0	33
CD8A	0.071	0.1	0.28	51	-10000	0	51
CD8B	0.049	0.1	0.28	32	-0.55	2	34
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.11	0.18	-10000	0	-0.45	48	48
IL2RB	0.047	0.077	0.25	31	-10000	0	31
proteasomal ubiquitin-dependent protein catabolic process	0.18	0.29	0.7	46	-10000	0	46
IL2RG	0.038	0.088	0.25	26	-0.55	2	28
IL12	0.092	0.12	0.34	44	-10000	0	44
STAT5A	0.019	0.001	-10000	0	-10000	0	0
CD247	0.037	0.068	0.28	18	-10000	0	18
IL2	-0.016	0.002	-10000	0	-10000	0	0
SPHK2	0.019	0.004	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.056	0.071	0.23	27	-10000	0	27
IL12/IL12R/TYK2/JAK2	0.24	0.42	0.97	53	-0.59	1	54
MAP2K3	0.17	0.31	0.75	42	-0.62	4	46
RIPK2	0.018	0.005	-10000	0	-10000	0	0
MAP2K6	0.17	0.32	0.76	41	-0.58	4	45
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.001	0.006	-10000	0	-0.026	11	11
IL18RAP	0.034	0.05	0.3	7	-10000	0	7
IL12Rbeta1/TYK2	0.082	0.11	0.36	29	-10000	0	29
EOMES	-0.019	0.14	-10000	0	-0.69	5	5
STAT1 (dimer)	0.18	0.32	0.78	47	-10000	0	47
T cell proliferation	0.15	0.26	0.62	45	-10000	0	45
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.013	0.097	-10000	0	-0.55	7	7
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.008	0.13	-10000	0	-0.5	1	1
ATF2	0.16	0.3	0.7	41	-0.58	3	44

×

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	0.081	0.19	0.39	43	-0.46	7	50
FYN	0.07	0.21	0.42	41	-0.57	7	48
LAT/GRAP2/SLP76	0.066	0.19	0.45	30	-0.48	6	36
IKBKB	0.019	0.004	-10000	0	-10000	0	0
AKT1	0.077	0.2	0.42	44	-0.37	9	53
B2M	0.022	0.013	-10000	0	-10000	0	0
IKBKG	0.025	0.078	0.2	28	-0.14	2	30
MAP3K8	0.018	0.004	-10000	0	-10000	0	0
mol:Ca2+	-0.024	0.03	-10000	0	-0.081	48	48
integrin-mediated signaling pathway	0.025	0.011	0.17	1	-10000	0	1
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.082	0.23	0.47	42	-0.52	8	50
TRPV6	-0.11	0.33	1.2	8	-0.55	62	70
CD28	0.038	0.063	0.26	19	-10000	0	19
SHC1	0.072	0.22	0.41	47	-0.43	15	62
receptor internalization	0.065	0.21	0.44	37	-0.48	14	51
PRF1	0.042	0.28	0.59	25	-0.66	17	42
KRAS	0.018	0.004	-10000	0	-10000	0	0
GRB2	0.019	0.003	-10000	0	-10000	0	0
COT/AKT1	0.076	0.17	0.38	44	-0.3	9	53
LAT	0.069	0.21	0.44	40	-0.42	16	56
EntrezGene:6955	0.003	0.008	-10000	0	-10000	0	0
CD3D	0.046	0.11	0.28	33	-0.56	3	36
CD3E	0.034	0.12	0.28	26	-0.56	6	32
CD3G	0.081	0.11	0.27	66	-10000	0	66
RASGRP2	0.013	0.051	0.14	19	-0.17	8	27
RASGRP1	0.083	0.2	0.43	45	-0.4	7	52
HLA-A	0.005	0.011	0.038	16	-10000	0	16
RASSF5	0.02	0.015	0.25	1	-10000	0	1
RAP1A/GTP/RAPL	0.026	0.011	0.17	1	-10000	0	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.066	0.12	0.25	59	-0.13	3	62
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.014	0.04	-10000	0	-0.21	4	4
PRKCA	0.029	0.11	0.27	26	-0.25	5	31
GRAP2	0.027	0.044	0.25	9	-10000	0	9
mol:IP3	0.049	0.14	0.27	54	-0.38	5	59
EntrezGene:6957	0.004	0.01	0.037	8	-10000	0	8
TCR/CD3/MHC I/CD8	0.058	0.18	0.39	41	-0.38	13	54
ORAI1	0.047	0.23	0.63	2	-1	8	10
CSK	0.065	0.21	0.44	39	-0.55	8	47
B7 family/CD28	0.1	0.22	0.54	34	-0.5	6	40
CHUK	0.018	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	0.067	0.23	0.48	36	-0.47	16	52
PTPN6	0.058	0.2	0.42	38	-0.47	11	49
VAV1	0.073	0.22	0.45	42	-0.43	15	57
Monovalent TCR/CD3	0.057	0.14	0.31	40	-0.4	6	46
CBL	0.018	0.005	-10000	0	-10000	0	0
LCK	0.065	0.21	0.43	39	-0.49	11	50
PAG1	0.065	0.21	0.42	41	-0.42	16	57
RAP1A	0.019	0.003	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	0.063	0.22	0.46	36	-0.45	16	52
CD80	0.037	0.062	0.26	18	-10000	0	18
CD86	0.022	0.016	0.26	1	-10000	0	1
PDK1/CARD11/BCL10/MALT1	-0.002	0.053	0.13	2	-0.24	5	7
HRAS	0.019	0.004	-10000	0	-10000	0	0
GO:0035030	0.067	0.19	0.42	39	-0.42	6	45
CD8A	0.069	0.1	0.27	51	-10000	0	51
CD8B	0.047	0.1	0.28	32	-0.56	2	34
PTPRC	0.03	0.067	0.26	14	-0.56	1	15
PDK1/PKC theta	0.08	0.22	0.44	46	-0.45	8	54
CSK/PAG1	0.064	0.21	0.43	39	-0.57	7	46
SOS1	0.019	0.004	-10000	0	-10000	0	0
peptide-MHC class I	0.02	0.02	-10000	0	-10000	0	0
GRAP2/SLP76	0.079	0.21	0.48	34	-0.51	8	42
STIM1	0.03	0.17	1.3	3	-1	1	4
RAS family/GTP	0.063	0.14	0.3	48	-0.18	7	55
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	0.065	0.22	0.46	36	-0.5	14	50
mol:DAG	-0.004	0.08	0.13	10	-0.32	6	16
RAP1A/GDP	0.034	0.062	0.13	50	-0.065	1	51
PLCG1	0.018	0.004	-10000	0	-10000	0	0
CD247	0.037	0.068	0.28	18	-10000	0	18
cytotoxic T cell degranulation	0.043	0.28	0.59	25	-0.62	19	44
RAP1A/GTP	0	0.012	-10000	0	-0.064	8	8
mol:PI-3-4-5-P3	0.082	0.21	0.45	43	-0.43	8	51
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.063	0.18	0.31	53	-0.5	5	58
NRAS	0.019	0.003	-10000	0	-10000	0	0
ZAP70	0.053	0.082	0.26	36	-10000	0	36
GRB2/SOS1	0.027	0.007	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	0.041	0.18	0.49	18	-0.47	6	24
MALT1	0.019	0.004	-10000	0	-10000	0	0
TRAF6	0.019	0.004	-10000	0	-10000	0	0
CD8 heterodimer	0.084	0.13	0.38	33	-0.42	2	35
CARD11	0.036	0.062	0.25	19	-10000	0	19
PRKCB	0.027	0.12	0.27	25	-0.27	6	31
PRKCE	0.03	0.11	0.27	26	-0.26	4	30
PRKCQ	0.08	0.23	0.46	45	-0.49	9	54
LCP2	0.021	0.026	0.25	3	-10000	0	3
BCL10	0.019	0.004	-10000	0	-10000	0	0
regulation of survival gene product expression	0.076	0.18	0.4	45	-0.32	9	54
IKK complex	0.057	0.12	0.24	55	-0.11	1	56
RAS family/GDP	-0.001	0.009	-10000	0	-10000	0	0
MAP3K14	0.061	0.15	0.34	44	-0.25	6	50
PDPK1	0.077	0.19	0.42	43	-0.35	8	51
TCR/CD3/MHC I/CD8/Fyn	0.054	0.24	0.47	35	-0.59	15	50

×

Aurora B 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
Condensin I complex	0.096	0.11	0.24	67	-10000	0	67
STMN1	0.05	0.081	0.33	4	-10000	0	4
Aurora B/RasGAP/Survivin	0.15	0.13	0.33	75	-10000	0	75
Chromosomal passenger complex/Cul3 protein complex	0.056	0.095	0.21	40	-0.22	1	41
BIRC5	0.14	0.12	0.26	121	-10000	0	121
DES	-0.21	0.29	-10000	0	-0.56	69	69
Aurora C/Aurora B/INCENP	0.089	0.075	0.28	4	-10000	0	4
Aurora B/TACC1	0.07	0.069	-10000	0	-10000	0	0
Aurora B/PP2A	0.081	0.078	0.2	3	-10000	0	3
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	0.023	0.029	0.17	2	-10000	0	2
mitotic metaphase/anaphase transition	-0.005	0.006	-10000	0	-10000	0	0
NDC80	0.094	0.13	0.3	58	-10000	0	58
Cul3 protein complex	0.002	0.1	-10000	0	-0.35	20	20
KIF2C	0.11	0.11	0.24	102	-10000	0	102
PEBP1	0.021	0.005	-10000	0	-10000	0	0
KIF20A	0.13	0.12	0.25	128	-10000	0	128
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.086	0.079	-10000	0	-10000	0	0
SEPT1	0.022	0.029	0.25	4	-10000	0	4
SMC2	0.019	0.004	-10000	0	-10000	0	0
SMC4	0.021	0.021	0.25	2	-10000	0	2
NSUN2/NPM1/Nucleolin	0.063	0.15	0.32	7	-0.48	11	18
PSMA3	0.019	0.004	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.003	0.005	-10000	0	-10000	0	0
H3F3B	0.051	0.059	0.24	2	-10000	0	2
AURKB	0.1	0.12	0.26	94	-10000	0	94
AURKC	0.022	0.026	0.25	3	-10000	0	3
CDCA8	0.1	0.11	0.26	87	-10000	0	87
cytokinesis	0.087	0.13	0.3	56	-10000	0	56
Aurora B/Septin1	0.13	0.15	0.34	67	-10000	0	67
AURKA	0.011	0.046	0.25	8	-10000	0	8
INCENP	0.028	0.022	0.27	2	-10000	0	2
KLHL13	-0.026	0.15	-10000	0	-0.55	20	20
BUB1	0.1	0.12	0.25	98	-10000	0	98
hSgo1/Aurora B/Survivin	0.16	0.15	0.35	82	-10000	0	82
EVI5	0.024	0.006	-10000	0	-10000	0	0
RhoA/GTP	0.12	0.12	0.3	51	-10000	0	51
SGOL1	0.055	0.085	0.25	39	-10000	0	39
CENPA	0.13	0.13	0.27	98	-0.3	3	101
NCAPG	0.12	0.12	0.25	115	-10000	0	115
Aurora B/HC8 Proteasome	0.085	0.079	0.2	1	-10000	0	1
NCAPD2	0.018	0.005	-10000	0	-10000	0	0
Aurora B/PP1-gamma	0.083	0.079	-10000	0	-10000	0	0
RHOA	0.019	0.004	-10000	0	-10000	0	0
NCAPH	0.1	0.11	0.25	90	-10000	0	90
NPM1	0.052	0.1	0.25	3	-10000	0	3
RASA1	0.019	0.002	-10000	0	-10000	0	0
KLHL9	0.017	0.006	-10000	0	-10000	0	0
mitotic prometaphase	0.002	0.003	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.085	0.079	0.2	1	-10000	0	1
PPP1CC	0.018	0.004	-10000	0	-10000	0	0
Centraspindlin	0.14	0.13	0.31	72	-10000	0	72
RhoA/GDP	0.014	0.003	-10000	0	-10000	0	0
NSUN2	0.049	0.12	0.25	6	-0.82	1	7
MYLK	-0.003	0.13	-10000	0	-0.28	39	39
KIF23	0.048	0.074	0.26	27	-10000	0	27
VIM	0.048	0.081	0.39	3	-10000	0	3
RACGAP1	0.026	0.023	0.27	2	-10000	0	2
mitosis	0	0	-10000	0	-10000	0	0
NCL	0.038	0.11	-10000	0	-0.83	1	1
Chromosomal passenger complex	0.14	0.13	0.28	110	-10000	0	110
Chromosomal passenger complex/EVI5	0.21	0.17	0.4	95	-10000	0	95
TACC1	0.018	0.005	-10000	0	-10000	0	0
PPP2R5D	0.018	0.005	-10000	0	-10000	0	0
CUL3	0.018	0.005	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

Reelin signaling pathway

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
CDK5R1/CDK5	0.031	0.028	-10000	0	-10000	0	0
VLDLR	-0.013	0.13	-10000	0	-0.55	14	14
CRKL	0.018	0.005	-10000	0	-10000	0	0
LRPAP1	0.019	0.004	-10000	0	-10000	0	0
FYN	0.018	0.005	-10000	0	-10000	0	0
ITGA3	-0.001	0.1	-10000	0	-0.55	9	9
RELN/VLDLR/Fyn	-0.067	0.18	-10000	0	-0.38	59	59
MAPK8IP1/MKK7/MAP3K11/JNK1	0.043	0.04	-10000	0	-0.31	2	2
AKT1	-0.065	0.13	-10000	0	-0.28	58	58
MAP2K7	0.018	0.004	-10000	0	-10000	0	0
RAPGEF1	0.019	0.004	-10000	0	-10000	0	0
DAB1	0.035	0.078	0.25	28	-10000	0	28
RELN/LRP8/DAB1	-0.024	0.16	0.38	4	-0.31	55	59
LRPAP1/LRP8	0.035	0.037	0.19	13	-10000	0	13
RELN/LRP8/DAB1/Fyn	-0.018	0.16	0.37	4	-0.3	53	57
DAB1/alpha3/beta1 Integrin	-0.053	0.16	0.31	2	-0.32	63	65
long-term memory	-0.048	0.18	0.31	7	-0.33	66	73
DAB1/LIS1	-0.035	0.17	0.34	4	-0.32	58	62
DAB1/CRLK/C3G	-0.044	0.16	0.31	2	-0.32	57	59
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
DAB1/NCK2	-0.033	0.18	0.35	4	-0.32	59	63
ARHGEF2	0.018	0.004	-10000	0	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	-0.039	0.21	0.25	18	-0.55	33	51
CDK5R1	0.026	0.039	0.25	7	-10000	0	7
RELN	-0.11	0.24	0.25	4	-0.55	57	61
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
RELN/LRP8/Fyn	-0.04	0.16	0.33	2	-0.35	53	55
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.044	0.2	0.36	7	-0.33	70	77
MAPK8	0.016	0.036	-10000	0	-0.55	1	1
RELN/VLDLR/DAB1	-0.051	0.18	0.31	3	-0.34	61	64
ITGB1	0.019	0.004	-10000	0	-10000	0	0
MAP1B	-0.072	0.16	0.23	3	-0.33	59	62
RELN/LRP8	-0.042	0.17	0.33	2	-0.35	55	57
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.014	0.16	0.38	4	-0.3	51	55
PI3K	0.028	0.017	-10000	0	-0.17	1	1
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.012	0.08	-10000	0	-0.41	9	9
RAP1A	-0.045	0.17	0.31	12	-0.32	51	63
PAFAH1B1	0.018	0.005	-10000	0	-10000	0	0
MAPK8IP1	0.016	0.036	-10000	0	-0.55	1	1
CRLK/C3G	0.026	0.009	-10000	0	-10000	0	0
GRIN2B	-0.016	0.004	-10000	0	-10000	0	0
NCK2	0.019	0.002	-10000	0	-10000	0	0
neuron differentiation	-0.021	0.1	0.21	3	-0.42	3	6
neuron adhesion	-0.055	0.17	0.34	9	-0.5	6	15
LRP8	0.031	0.052	0.25	13	-10000	0	13
GSK3B	-0.066	0.12	-10000	0	-0.44	7	7
RELN/VLDLR/DAB1/Fyn	-0.042	0.17	0.31	3	-0.33	58	61
MAP3K11	0.019	0.003	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.061	0.14	0.18	3	-0.29	59	62
CDK5	0.018	0.005	-10000	0	-10000	0	0
MAPT	-0.18	0.27	0.76	3	-0.5	98	101
neuron migration	-0.063	0.18	0.3	11	-0.36	52	63
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.021	0.1	0.21	3	-0.42	3	6
RELN/VLDLR	-0.05	0.18	0.33	2	-0.35	60	62

×

IL23-mediated signaling events

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
CCL2	0.004	0.53	0.81	14	-1.3	22	36
IL23A	0.038	0.47	0.87	14	-1.2	16	30
NF kappa B1 p50/RelA/I kappa B alpha	-0.021	0.4	0.76	1	-1	22	23
positive regulation of T cell mediated cytotoxicity	0.043	0.52	0.88	20	-1.1	23	43
ITGA3	0.004	0.48	0.78	15	-1.1	23	38
IL17F	0.037	0.33	0.54	27	-0.67	22	49
IL12B	0.056	0.11	0.34	20	-10000	0	20
STAT1 (dimer)	0.022	0.47	0.71	18	-1.1	23	41
CD4	0.043	0.45	0.82	13	-1.1	16	29
IL23	0.027	0.45	0.8	12	-1.1	16	28
IL23R	0.07	0.18	0.6	8	-0.75	2	10
IL1B	0.027	0.5	0.85	16	-1.3	18	34
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	0.036	0.45	0.76	19	-1.1	17	36
TYK2	0.027	0.054	0.26	1	-10000	0	1
STAT4	0.026	0.041	0.25	8	-10000	0	8
STAT3	0.019	0.001	-10000	0	-10000	0	0
IL18RAP	0.029	0.043	0.27	7	-10000	0	7
IL12RB1	0.048	0.1	0.35	21	-10000	0	21
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	0.049	0.093	0.3	20	-10000	0	20
IL23R/JAK2	0.084	0.19	0.55	9	-0.85	1	10
positive regulation of chronic inflammatory response	0.043	0.52	0.88	20	-1.1	23	43
natural killer cell activation	-0.007	0.017	-10000	0	-0.053	14	14
JAK2	0.045	0.08	0.27	9	-10000	0	9
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
NFKB1	0.015	0.019	-10000	0	-10000	0	0
RELA	0.015	0.019	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	0.032	0.43	0.76	16	-1.1	16	32
ALOX12B	0.043	0.45	0.77	18	-1.1	17	35
CXCL1	-0.083	0.64	0.85	15	-1.2	52	67
T cell proliferation	0.043	0.52	0.88	20	-1.1	23	43
NFKBIA	0.014	0.019	-10000	0	-10000	0	0
IL17A	0.055	0.29	0.5	34	-0.55	16	50
PI3K	0	0.43	0.63	5	-1.1	23	28
IFNG	0.037	0.082	0.17	56	-0.12	2	58
STAT3 (dimer)	-0.006	0.41	0.58	1	-1	23	24
IL18R1	0.007	0.094	-10000	0	-0.55	7	7
IL23/IL23R/JAK2/TYK2/SOCS3	0.082	0.32	0.64	29	-0.61	5	34
IL18/IL18R	0.036	0.12	0.28	7	-0.35	16	23
macrophage activation	0.004	0.03	0.059	33	-0.045	4	37
TNF	0.041	0.47	0.87	15	-1.1	16	31
STAT3/STAT4	0.017	0.45	0.75	11	-1	23	34
STAT4 (dimer)	0.027	0.48	0.79	16	-1.1	23	39
IL18	0.001	0.11	-10000	0	-0.55	9	9
IL19	0.037	0.45	0.81	13	-1.1	15	28
STAT5A (dimer)	0.023	0.47	0.74	13	-1.1	23	36
STAT1	0.02	0.015	0.25	1	-10000	0	1
SOCS3	0.019	0.004	-10000	0	-10000	0	0
CXCL9	0.066	0.49	0.82	26	-1.1	16	42
MPO	0.053	0.46	0.8	17	-1.1	16	33
positive regulation of humoral immune response	0.043	0.52	0.88	20	-1.1	23	43
IL23/IL23R/JAK2/TYK2	0.035	0.54	0.88	20	-1.2	23	43
IL6	-0.015	0.57	0.8	16	-1.3	31	47
STAT5A	0.019	0.001	-10000	0	-10000	0	0
IL2	0.013	0.04	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	-0.007	0.017	-10000	0	-0.053	14	14
CD3E	0.038	0.49	0.82	23	-1.2	19	42
keratinocyte proliferation	0.043	0.52	0.88	20	-1.1	23	43
NOS2	0.031	0.46	0.81	13	-1.1	17	30

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.02	0.042	0.14	4	-0.1	39	43
BUB1B	0.063	0.062	0.14	80	-10000	0	80
PLK1	0.025	0.031	0.096	19	-10000	0	19
PLK1S1	0.012	0.041	-10000	0	-0.18	9	9
KIF2A	0.019	0.034	0.25	2	-10000	0	2
regulation of mitotic centrosome separation	0.025	0.031	0.095	19	-10000	0	19
GOLGA2	0.019	0.003	-10000	0	-10000	0	0
Hec1/SPC24	0.13	0.13	0.28	92	-10000	0	92
WEE1	0.019	0.064	-10000	0	-0.32	7	7
cytokinesis	0.086	0.086	0.2	61	-0.23	1	62
PP2A-alpha B56	0.083	0.08	-10000	0	-0.46	2	2
AURKA	0.022	0.031	0.12	13	-0.16	1	14
PICH/PLK1	0.044	0.079	0.19	47	-10000	0	47
CENPE	0.039	0.051	0.15	18	-10000	0	18
RhoA/GTP	0.014	0.003	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.019	0.034	0.25	2	-10000	0	2
PPP2CA	0.019	0.003	-10000	0	-10000	0	0
FZR1	0.019	0.004	-10000	0	-10000	0	0
TPX2	0.061	0.056	0.12	82	-0.19	1	83
PAK1	0.018	0.004	-10000	0	-10000	0	0
SPC24	0.12	0.12	0.25	106	-10000	0	106
FBXW11	0.019	0.004	-10000	0	-10000	0	0
CLSPN	0.062	0.065	0.13	91	-0.23	3	94
GORASP1	0.019	0.003	-10000	0	-10000	0	0
metaphase	0	0.002	0.013	4	-0.011	1	5
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.013	0.017	0.054	15	-10000	0	15
G2 phase of mitotic cell cycle	-0.001	0.002	0.013	3	-10000	0	3
STAG2	0.019	0.002	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.006	0.07	-10000	0	-0.49	5	5
spindle elongation	0.025	0.031	0.095	19	-10000	0	19
ODF2	0.019	0.005	-10000	0	-10000	0	0
BUB1	0.075	0.091	0.34	1	-0.49	2	3
TPT1	-0.007	0.069	-10000	0	-0.18	32	32
CDC25C	0.11	0.056	0.15	90	-0.25	1	91
CDC25B	0.02	0.006	-10000	0	-10000	0	0
SGOL1	0.02	0.042	0.1	39	-0.14	4	43
RHOA	0.019	0.004	-10000	0	-10000	0	0
CCNB1/CDK1	0.037	0.048	-10000	0	-10000	0	0
CDC14B	-0.01	0.036	-10000	0	-0.41	2	2
CDC20	0.097	0.11	0.25	85	-10000	0	85
PLK1/PBIP1	0.017	0.031	0.13	10	-10000	0	10
mitosis	-0.001	0.003	0.026	1	-10000	0	1
FBXO5	0.023	0.043	0.15	16	-10000	0	16
CDC2	0.001	0.003	0.01	19	-10000	0	19
NDC80	0.086	0.11	0.25	74	-10000	0	74
metaphase plate congression	0.015	0.05	-10000	0	-0.24	8	8
ERCC6L	0.044	0.072	0.23	17	-10000	0	17
NLP/gamma Tubulin	0.015	0.019	0.074	4	-0.1	1	5
microtubule cytoskeleton organization	-0.007	0.068	-10000	0	-0.18	32	32
G2/M transition DNA damage checkpoint	-0.001	0.002	0.013	1	-10000	0	1
PPP1R12A	0.018	0.006	-10000	0	-10000	0	0
interphase	-0.001	0.002	0.013	1	-10000	0	1
PLK1/PRC1-2	0.14	0.13	0.26	122	-10000	0	122
GRASP65/GM130/RAB1/GTP/PLK1	0.044	0.027	-10000	0	-10000	0	0
RAB1A	0.019	0.003	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.018	0.026	0.083	20	-10000	0	20
mitotic prometaphase	0.001	0.003	0.018	8	-10000	0	8
proteasomal ubiquitin-dependent protein catabolic process	0.026	0.063	0.21	2	-0.33	1	3
microtubule-based process	0.11	0.093	0.2	128	-10000	0	128
Golgi organization	0.025	0.031	0.095	19	-10000	0	19
Cohesin/SA2	0.032	0.024	-10000	0	-10000	0	0
PPP1CB/MYPT1	0.026	0.009	-10000	0	-10000	0	0
KIF20A	0.14	0.12	0.25	128	-10000	0	128
APC/C/CDC20	0.085	0.09	0.21	85	-10000	0	85
PPP2R1A	0.019	0.004	-10000	0	-10000	0	0
chromosome segregation	0.016	0.03	0.12	10	-10000	0	10
PRC1	0.073	0.1	0.25	59	-10000	0	59
ECT2	0.019	0.036	0.22	3	-10000	0	3
C13orf34	0.019	0.025	0.081	18	-10000	0	18
NUDC	0.015	0.05	-10000	0	-0.24	8	8
regulation of attachment of spindle microtubules to kinetochore	0.063	0.062	0.13	80	-10000	0	80
spindle assembly	0.019	0.025	0.081	13	-10000	0	13
spindle stabilization	0.012	0.041	-10000	0	-0.18	9	9
APC/C/HCDH1	0.012	0.032	-10000	0	-0.35	2	2
MKLP2/PLK1	0.11	0.093	0.2	128	-10000	0	128
CCNB1	0.037	0.064	0.25	20	-10000	0	20
PPP1CB	0.019	0.005	-10000	0	-10000	0	0
BTRC	0.018	0.005	-10000	0	-10000	0	0
ROCK2	0.011	0.061	-10000	0	-0.26	8	8
TUBG1	0.017	0.022	-10000	0	-0.22	1	1
G2/M transition of mitotic cell cycle	0.015	0.04	0.19	2	-10000	0	2
MLF1IP	0.001	0.033	0.15	12	-10000	0	12
INCENP	0.021	0.021	0.25	2	-10000	0	2

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	0.038	0.086	0.28	2	-0.4	4	6
alphaM/beta2 Integrin/GPIbA	0.029	0.064	0.26	3	-0.42	2	5
alphaM/beta2 Integrin/proMMP-9	0.081	0.11	0.29	13	-0.38	3	16
PLAUR	0.049	0.079	0.25	33	-10000	0	33
HMGB1	0.012	0.024	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Talin	0.028	0.061	0.22	1	-0.42	2	3
AGER	0.013	0.025	-10000	0	-10000	0	0
RAP1A	0.019	0.003	-10000	0	-10000	0	0
SELPLG	0.024	0.036	0.25	6	-10000	0	6
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	0.025	0.1	0.31	3	-0.25	21	24
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	0.11	0.12	0.25	100	-0.55	1	101
CYR61	0.012	0.061	-10000	0	-0.55	3	3
TLN1	0.018	0.005	-10000	0	-10000	0	0
Rap1/GTP	-0.054	0.13	-10000	0	-0.43	15	15
RHOA	0.019	0.004	-10000	0	-10000	0	0
P-selectin oligomer	-0.15	0.26	-10000	0	-0.55	75	75
MYH2	-0.16	0.2	0.23	3	-0.46	53	56
MST1R	0.035	0.06	0.25	18	-10000	0	18
leukocyte activation during inflammatory response	-0.069	0.17	-10000	0	-0.32	70	70
APOB	-0.11	0.23	0.25	2	-0.55	54	56
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	0.035	0.086	0.25	23	-0.55	2	25
JAM3	0.018	0.005	-10000	0	-10000	0	0
GP1BA	0.019	0.022	0.25	2	-10000	0	2
alphaM/beta2 Integrin/CTGF	0.016	0.091	0.22	1	-0.38	10	11
alphaM/beta2 Integrin	-0.068	0.15	0.2	3	-0.42	22	25
JAM3 homodimer	0.018	0.005	-10000	0	-10000	0	0
ICAM2	0.019	0.003	-10000	0	-10000	0	0
ICAM1	0.019	0.016	0.25	1	-10000	0	1
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.067	0.15	0.2	3	-0.41	22	25
cell adhesion	0.028	0.063	0.26	3	-0.42	2	5
NFKB1	-0.029	0.15	0.39	8	-0.41	24	32
THY1	0.016	0.036	-10000	0	-0.55	1	1
RhoA/GDP	0.014	0.003	-10000	0	-10000	0	0
Lipoprotein(a)	-0.09	0.18	-10000	0	-0.37	73	73
alphaM/beta2 Integrin/LRP/tPA	0.029	0.09	0.33	1	-0.4	7	8
IL6	-0.07	0.26	0.45	7	-0.78	26	33
ITGB2	0.019	0.047	0.26	7	-10000	0	7
elevation of cytosolic calcium ion concentration	0.055	0.086	0.34	4	-0.39	2	6
alphaM/beta2 Integrin/JAM2/JAM3	0.035	0.061	-10000	0	-0.39	2	2
JAM2	0.019	0.004	-10000	0	-10000	0	0
alphaM/beta2 Integrin/ICAM1	0.051	0.073	0.4	1	-0.36	2	3
alphaM/beta2 Integrin/uPA/Plg	-0.033	0.16	0.33	1	-0.33	50	51
RhoA/GTP	-0.089	0.18	0.23	2	-0.5	22	24
positive regulation of phagocytosis	-0.036	0.13	0.31	7	-0.42	11	18
Ron/MSP	0.035	0.059	-10000	0	-0.41	2	2
alphaM/beta2 Integrin/uPAR/uPA	0.057	0.088	0.35	4	-0.39	2	6
alphaM/beta2 Integrin/uPAR	0.047	0.082	0.27	5	-0.42	2	7
PLAU	0.026	0.044	0.25	9	-10000	0	9
PLAT	0.006	0.088	0.25	1	-0.55	6	7
actin filament polymerization	-0.15	0.19	0.23	4	-0.44	53	57
MST1	0.014	0.05	-10000	0	-0.55	2	2
alphaM/beta2 Integrin/lipoprotein(a)	-0.067	0.17	-10000	0	-0.33	70	70
TNF	-0.033	0.14	0.39	6	-0.39	20	26
RAP1B	0.017	0.007	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPA	0.033	0.068	0.28	2	-0.42	2	4
fibrinolysis	-0.034	0.16	0.32	1	-0.33	50	51
HCK	0.03	0.05	0.25	12	-10000	0	12
dendritic cell antigen processing and presentation	-0.067	0.15	0.2	3	-0.41	22	25
VTN	-0.11	0.24	0.25	1	-0.55	57	58
alphaM/beta2 Integrin/CYR61	0.025	0.074	-10000	0	-0.38	5	5
LPA	-0.058	0.16	-10000	0	-0.55	25	25
LRP1	0.023	0.033	0.25	5	-10000	0	5
cell migration	0.057	0.096	0.23	20	-0.35	5	25
FN1	0.063	0.092	0.25	48	-10000	0	48
alphaM/beta2 Integrin/Thy1	0.027	0.066	0.22	1	-0.4	3	4
MPO	0.047	0.079	0.25	32	-10000	0	32
KNG1	-0.14	0.22	-10000	0	-0.55	58	58
RAP1/GDP	0.022	0.01	-10000	0	-10000	0	0
ROCK1	-0.085	0.17	0.23	3	-0.47	22	25
ELA2	0	0	-10000	0	-10000	0	0
PLG	-0.12	0.21	-10000	0	-0.55	50	50
CTGF	0	0.099	-10000	0	-0.55	8	8
alphaM/beta2 Integrin/Hck	0.035	0.074	0.3	6	-0.42	2	8
ITGAM	0.009	0.061	0.26	1	-0.6	2	3
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.066	0.18	-10000	0	-0.33	72	72
HP	0.036	0.072	0.25	24	-10000	0	24
leukocyte adhesion	0.008	0.093	0.27	1	-0.4	4	5
SELP	-0.15	0.26	-10000	0	-0.55	75	75

×

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	-0.062	0.13	-10000	0	-0.31	47	47
NF kappa B1 p50/RelA/I kappa B alpha	-0.053	0.13	-10000	0	-0.43	5	5
alphaV/beta3 Integrin/Osteopontin/Src	-0.047	0.17	-10000	0	-0.4	46	46
AP1	-0.029	0.16	0.37	1	-0.46	7	8
ILK	-0.066	0.13	-10000	0	-0.33	46	46
bone resorption	-0.067	0.13	-10000	0	-0.6	3	3
PTK2B	0.018	0.004	-10000	0	-10000	0	0
PYK2/p130Cas	-0.024	0.15	-10000	0	-0.32	47	47
ITGAV	0.021	0.006	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.027	0.013	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.032	0.16	-10000	0	-0.36	48	48
MAP3K1	-0.068	0.13	-10000	0	-0.33	47	47
JUN	0.018	0.007	-10000	0	-10000	0	0
MAPK3	-0.064	0.13	-10000	0	-0.31	47	47
MAPK1	-0.064	0.13	-10000	0	-0.31	47	47
Rac1/GDP	0.013	0.004	-10000	0	-10000	0	0
NFKB1	0.019	0.001	-10000	0	-10000	0	0
MAPK8	-0.066	0.13	-10000	0	-0.31	47	47
ITGB3	0.01	0.078	-10000	0	-0.54	5	5
NFKBIA	-0.059	0.13	0.27	1	-0.36	16	17
FOS	-0.004	0.11	-10000	0	-0.55	10	10
CD44	0.02	0.015	0.25	1	-10000	0	1
CHUK	0.018	0.005	-10000	0	-10000	0	0
PLAU	-0.045	0.14	0.41	1	-0.51	2	3
NF kappa B1 p50/RelA	-0.055	0.13	0.33	2	-0.52	2	4
BCAR1	0.018	0.005	-10000	0	-10000	0	0
RELA	0.019	0.003	-10000	0	-10000	0	0
alphaV beta3 Integrin	0.023	0.06	-10000	0	-0.4	5	5
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	-0.071	0.14	-10000	0	-0.34	47	47
VAV3	-0.071	0.14	-10000	0	-0.33	46	46
MAP3K14	-0.066	0.13	-10000	0	-0.33	47	47
ROCK2	0.019	0.004	-10000	0	-10000	0	0
SPP1	-0.081	0.22	-10000	0	-0.55	46	46
RAC1	0.018	0.006	-10000	0	-10000	0	0
Rac1/GTP	-0.067	0.13	-10000	0	-0.31	45	45
MMP2	-0.037	0.16	0.36	6	-0.48	6	12

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.005	0.066	-10000	0	-0.38	5	5
Crk/p130 Cas/Paxillin	-0.057	0.1	-10000	0	-0.3	27	27
JUN	-0.021	0.11	0.23	6	-0.39	6	12
HRAS	0.019	0.004	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	0.014	0.15	0.33	3	-0.32	31	34
RAP1A	0.019	0.003	-10000	0	-10000	0	0
FRS2	0.015	0.008	-10000	0	-10000	0	0
RAP1A/GDP	0.014	0.002	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	0.017	0.15	0.33	3	-0.33	29	32
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.018	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.018	0.005	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	0.008	0.13	0.31	2	-0.3	29	31
RHOA	0.019	0.004	-10000	0	-10000	0	0
RAP1A/GTP	0.007	0.14	0.27	3	-0.32	31	34
GRB7	-0.077	0.21	0.25	1	-0.55	42	43
RET51/GFRalpha1/GDNF	0.013	0.15	0.33	3	-0.33	30	33
MAPKKK cascade	-0.024	0.13	0.21	2	-0.34	23	25
BCAR1	0.018	0.005	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	0.006	0.13	0.31	1	-0.3	29	30
lamellipodium assembly	-0.033	0.11	-10000	0	-0.28	29	29
RET51/GFRalpha1/GDNF/SHC	0.013	0.15	0.33	3	-0.33	29	32
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	0.007	0.13	0.31	2	-0.3	27	29
RET9/GFRalpha1/GDNF/Shank3	0.007	0.13	0.31	1	-0.3	29	30
MAPK3	-0.026	0.13	0.22	2	-0.33	24	26
DOK1	0.019	0.004	-10000	0	-10000	0	0
DOK6	-0.14	0.26	-10000	0	-0.55	72	72
PXN	0.019	0.004	-10000	0	-10000	0	0
neurite development	-0.061	0.14	-10000	0	-0.43	18	18
DOK5	0	0.12	0.25	4	-0.55	10	14
GFRA1	-0.049	0.21	0.25	12	-0.55	35	47
MAPK8	-0.022	0.11	0.19	1	-0.29	25	26
HRAS/GTP	0.001	0.15	0.27	3	-0.35	29	32
tube development	0.008	0.13	0.32	3	-0.29	28	31
MAPK1	-0.028	0.12	0.22	2	-0.34	22	24
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.017	0.1	0.18	6	-0.24	28	34
Rac1/GDP	0.013	0.004	-10000	0	-10000	0	0
SRC	0.019	0.004	-10000	0	-10000	0	0
PDLIM7	0.018	0.004	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.073	0.22	0.32	2	-0.36	79	81
SHC1	0.018	0.004	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	0.013	0.16	0.33	3	-0.35	31	34
RET51/GFRalpha1/GDNF/Dok5	0.003	0.17	0.33	4	-0.35	35	39
PRKCA	0.019	0.004	-10000	0	-10000	0	0
HRAS/GDP	0.014	0.003	-10000	0	-10000	0	0
CREB1	-0.024	0.13	-10000	0	-0.34	26	26
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.016	0.098	0.18	1	-0.26	18	19
RET51/GFRalpha1/GDNF/Grb7	-0.036	0.2	0.33	4	-0.36	57	61
mol:GDP	0	0	-10000	0	-10000	0	0
RET	0.019	0.086	0.25	11	-0.55	4	15
DOK4	0.014	0.05	-10000	0	-0.55	2	2
JNK cascade	-0.016	0.11	0.24	5	-0.38	6	11
RET9/GFRalpha1/GDNF/FRS2	0.001	0.13	0.35	2	-0.3	28	30
SHANK3	0.018	0.004	-10000	0	-10000	0	0
RASA1	0.019	0.002	-10000	0	-10000	0	0
NCK1	0.019	0.002	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.016	0.1	-10000	0	-0.27	21	21
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.02	0.12	0.2	6	-0.29	25	31
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.018	0.12	0.2	1	-0.3	26	27
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.018	0.13	0.21	1	-0.32	24	25
PI3K	-0.033	0.17	0.29	3	-0.4	30	33
SOS1	0.019	0.004	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	0.012	0.13	0.31	1	-0.29	28	29
GRB10	0.018	0.005	-10000	0	-10000	0	0
activation of MAPKK activity	-0.012	0.1	0.19	5	-0.26	23	28
RET51/GFRalpha1/GDNF/FRS2	0.003	0.15	0.35	3	-0.32	31	34
GAB1	0.019	0.003	-10000	0	-10000	0	0
IRS1	0.019	0.016	0.25	1	-10000	0	1
IRS2	0.017	0.006	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.019	0.13	0.2	2	-0.33	23	25
RET51/GFRalpha1/GDNF/PKC alpha	0.016	0.15	0.33	2	-0.33	28	30
GRB2	0.019	0.003	-10000	0	-10000	0	0
PRKACA	0.018	0.005	-10000	0	-10000	0	0
GDNF	0.048	0.095	0.25	44	-10000	0	44
RAC1	0.018	0.006	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	0.012	0.15	0.33	2	-0.33	31	33
Rac1/GTP	-0.03	0.13	-10000	0	-0.33	29	29
RET9/GFRalpha1/GDNF	-0.001	0.14	0.18	43	-0.27	42	85
GFRalpha1/GDNF	-0.004	0.16	0.2	43	-0.32	42	85

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	0.088	0.12	0.35	37	-10000	0	37
NFATC2	0.11	0.17	0.5	22	-10000	0	22
NFATC3	-0.003	0.087	-10000	0	-0.27	7	7
CD40LG	0.044	0.29	0.65	14	-0.83	9	23
ITCH	-0.042	0.11	-10000	0	-10000	0	0
CBLB	-0.039	0.11	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	0.12	0.31	0.62	43	-0.85	7	50
JUNB	0.018	0.004	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.043	0.13	-10000	0	-0.31	50	50
T cell anergy	-0.063	0.17	-10000	0	-0.4	48	48
TLE4	0.067	0.1	0.35	11	-10000	0	11
Jun/NFAT1-c-4/p21SNFT	0.075	0.26	0.58	20	-0.89	7	27
AP-1/NFAT1-c-4	0.079	0.35	0.73	24	-0.94	9	33
IKZF1	0.074	0.13	0.52	11	-10000	0	11
T-helper 2 cell differentiation	0.02	0.23	0.43	5	-0.63	14	19
AP-1/NFAT1	0.076	0.18	0.43	25	-0.43	6	31
CALM1	-0.017	0.082	-10000	0	-10000	0	0
EGR2	0.05	0.26	0.56	8	-1	6	14
EGR3	0.037	0.3	0.57	7	-1.4	7	14
NFAT1/FOXP3	0.15	0.2	0.48	51	-10000	0	51
EGR1	0.014	0.062	-10000	0	-0.55	3	3
JUN	0.017	0.041	-10000	0	-10000	0	0
EGR4	0.023	0.036	0.26	5	-10000	0	5
mol:Ca2+	-0.031	0.071	-10000	0	-0.18	47	47
GBP3	0.065	0.1	0.37	6	-10000	0	6
FOSL1	0.036	0.062	0.25	19	-10000	0	19
NFAT1-c-4/MAF/IRF4	0.09	0.25	0.62	14	-0.84	8	22
DGKA	0.066	0.11	0.44	5	-10000	0	5
CREM	0.019	0.004	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	0.065	0.24	0.53	11	-0.85	9	20
CTLA4	0.14	0.2	0.44	68	-10000	0	68
NFAT1-c-4 (dimer)/EGR1	0.067	0.26	0.59	10	-0.88	9	19
NFAT1-c-4 (dimer)/EGR4	0.073	0.25	0.59	11	-0.84	9	20
FOS	-0.002	0.12	-10000	0	-0.55	10	10
IFNG	0.12	0.21	0.53	38	-0.55	1	39
T cell activation	0.054	0.16	0.54	3	-0.71	1	4
MAF	0.018	0.005	-10000	0	-10000	0	0
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.038	0.2	0.65	8	-0.5	6	14
TNF	0.046	0.23	0.57	10	-0.84	8	18
FASLG	0.048	0.31	0.65	8	-1.2	9	17
TBX21	0.088	0.13	0.36	44	-10000	0	44
BATF3	0.017	0.036	-10000	0	-0.55	1	1
PRKCQ	0.02	0.088	0.28	3	-0.55	5	8
PTPN1	0.064	0.1	0.36	7	-10000	0	7
NFAT1-c-4/ICER1	0.063	0.24	0.53	12	-0.85	9	21
GATA3	-0.029	0.16	-10000	0	-0.55	21	21
T-helper 1 cell differentiation	0.12	0.21	0.53	38	-0.54	1	39
IL2RA	0.12	0.31	0.58	46	-0.88	7	53
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	0.064	0.099	0.35	6	-10000	0	6
E2F1	0.1	0.11	0.26	78	-10000	0	78
PPARG	0.022	0.03	0.25	4	-10000	0	4
SLC3A2	0.065	0.099	0.35	6	-10000	0	6
IRF4	0.049	0.081	0.25	34	-10000	0	34
PTGS2	-0.018	0.34	0.58	12	-0.86	15	27
CSF2	0.04	0.28	0.57	14	-0.83	9	23
JunB/Fra1/NFAT1-c-4	0.077	0.24	0.52	15	-0.83	8	23
IL4	0.018	0.23	0.44	4	-0.66	14	18
IL5	0.034	0.28	0.56	12	-0.83	9	21
IL2	0.054	0.16	0.57	2	-0.72	1	3
IL3	-0.01	0.082	-10000	0	-0.76	2	2
RNF128	-0.12	0.26	0.29	1	-0.64	50	51
NFATC1	0.038	0.2	0.5	6	-0.65	8	14
CDK4	0.007	0.2	0.68	4	-10000	0	4
PTPRK	0.067	0.1	0.39	6	-10000	0	6
IL8	0.043	0.31	0.59	18	-0.87	10	28
POU2F1	0.019	0.016	0.25	1	-10000	0	1

×

Coregulation of Androgen receptor activity

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
NRIP1	0.007	0.034	-10000	0	-10000	0	0
SVIL	0.004	0.058	-10000	0	-0.55	2	2
ZNF318	0.036	0.054	0.19	27	-10000	0	27
JMJD2C	-0.035	0.061	-10000	0	-0.13	72	72
T-DHT/AR/Ubc9	-0.064	0.11	-10000	0	-0.41	10	10
CARM1	0.014	0.014	-10000	0	-10000	0	0
PRDX1	0.02	0.006	-10000	0	-10000	0	0
PELP1	0.02	0.011	-10000	0	-10000	0	0
CTNNB1	0.009	0.028	-10000	0	-10000	0	0
AKT1	0.022	0.015	-10000	0	-10000	0	0
PTK2B	0.01	0.025	-10000	0	-10000	0	0
MED1	0.024	0.016	-10000	0	-10000	0	0
MAK	0.037	0.058	0.22	7	-10000	0	7
response to oxidative stress	0.001	0.003	-10000	0	-10000	0	0
HIP1	0.006	0.047	-10000	0	-0.55	1	1
GSN	0.007	0.036	-10000	0	-10000	0	0
NCOA2	0.016	0.067	0.25	8	-0.55	2	10
NCOA6	0.009	0.031	-10000	0	-10000	0	0
DNA-PK	0.049	0.05	0.22	2	-10000	0	2
NCOA4	0.015	0.012	-10000	0	-10000	0	0
PIAS3	0.009	0.027	-10000	0	-10000	0	0
cell proliferation	-0.032	0.11	-10000	0	-0.47	11	11
XRCC5	0.022	0.013	-10000	0	-10000	0	0
UBE3A	0.004	0.044	-10000	0	-10000	0	0
T-DHT/AR/SNURF	-0.07	0.11	-10000	0	-0.38	14	14
FHL2	-0.039	0.071	-10000	0	-10000	0	0
RANBP9	0.007	0.032	-10000	0	-10000	0	0
JMJD1A	-0.078	0.071	-10000	0	-0.14	141	141
CDK6	0.016	0.036	-10000	0	-0.55	1	1
TGFB1I1	0.009	0.031	-10000	0	-10000	0	0
T-DHT/AR/CyclinD1	-0.072	0.11	-10000	0	-0.24	44	44
XRCC6	0.022	0.013	-10000	0	-10000	0	0
T-DHT/AR	-0.14	0.15	-10000	0	-0.36	49	49
CTDSP1	0.012	0.018	-10000	0	-10000	0	0
CTDSP2	0.023	0.032	-10000	0	-10000	0	0
BRCA1	0.01	0.037	0.21	2	-10000	0	2
TCF4	0.027	0.03	0.25	1	-10000	0	1
CDKN2A	0.19	0.11	0.26	182	-10000	0	182
SRF	0.025	0.019	-10000	0	-10000	0	0
NKX3-1	-0.15	0.12	-10000	0	-0.26	144	144
KLK3	-0.16	0.45	-10000	0	-1.4	28	28
TMF1	0.014	0.014	-10000	0	-10000	0	0
HNRNPA1	0.023	0.017	-10000	0	-10000	0	0
AOF2	-0.007	0.022	-10000	0	-0.07	28	28
APPL1	-0.003	0.034	-10000	0	-10000	0	0
T-DHT/AR/Caspase 8	-0.061	0.11	0.25	1	-0.24	34	35
AR	-0.052	0.14	0.23	18	-0.6	10	28
UBA3	0.013	0.018	-10000	0	-10000	0	0
PATZ1	0.023	0.017	-10000	0	-10000	0	0
PAWR	0.003	0.079	-10000	0	-0.55	5	5
PRKDC	0.022	0.013	-10000	0	-10000	0	0
PA2G4	0.025	0.023	-10000	0	-10000	0	0
UBE2I	0.019	0.002	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.054	0.096	0.23	1	-0.38	9	10
RPS6KA3	0.006	0.035	-10000	0	-10000	0	0
T-DHT/AR/ARA70	-0.067	0.11	-10000	0	-0.23	42	42
LATS2	0.023	0.019	-10000	0	-10000	0	0
T-DHT/AR/PRX1	-0.051	0.1	0.24	2	-0.37	10	12
Cyclin D3/CDK11 p58	0.014	0.006	-10000	0	-10000	0	0
VAV3	0.01	0.051	0.25	2	-0.59	1	3
KLK2	-0.31	0.44	-10000	0	-0.98	74	74
CASP8	0.021	0.008	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.056	0.11	0.25	3	-0.3	21	24
TMPRSS2	-0.55	0.48	-10000	0	-0.98	142	142
CCND1	0.009	0.041	-10000	0	-0.55	1	1
PIAS1	0.004	0.043	-10000	0	-10000	0	0
mol:T-DHT	-0.054	0.042	-10000	0	-0.081	166	166
CDC2L1	0.001	0.002	-10000	0	-10000	0	0
PIAS4	0	0.06	-10000	0	-0.19	13	13
T-DHT/AR/CDK6	-0.059	0.11	0.21	1	-0.23	41	42
CMTM2	0.022	0.031	0.25	4	-10000	0	4
SNURF	0.009	0.071	-10000	0	-0.55	4	4
ZMIZ1	-0.052	0.056	-10000	0	-0.19	1	1
CCND3	0.018	0.006	-10000	0	-10000	0	0
TGIF1	0.023	0.015	-10000	0	-10000	0	0
FKBP4	0.008	0.031	-10000	0	-10000	0	0

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.019	0.016	0.25	1	-10000	0	1
CCL5	0.056	0.086	0.25	40	-10000	0	40
SDCBP	0.018	0.005	-10000	0	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.026	0.16	0.26	11	-0.37	12	23
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	-0.025	0.15	0.27	4	-0.37	9	13
Syndecan-1/Syntenin	-0.022	0.15	0.3	4	-0.37	9	13
MAPK3	-0.037	0.13	0.25	3	-0.39	6	9
HGF/MET	0.004	0.096	-10000	0	-0.41	13	13
TGFB1/TGF beta receptor Type II	0.019	0.016	0.25	1	-10000	0	1
BSG	0.018	0.005	-10000	0	-10000	0	0
keratinocyte migration	-0.024	0.15	0.27	4	-0.37	9	13
Syndecan-1/RANTES	-0.003	0.17	0.27	30	-0.39	9	39
Syndecan-1/CD147	-0.024	0.15	0.33	1	-0.39	7	8
Syndecan-1/Syntenin/PIP2	-0.024	0.14	0.26	3	-0.36	9	12
LAMA5	0.018	0.005	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	-0.025	0.14	0.23	2	-0.35	9	11
MMP7	-0.17	0.26	-10000	0	-0.55	84	84
HGF	-0.004	0.11	-10000	0	-0.55	10	10
Syndecan-1/CASK	-0.041	0.14	0.21	5	-0.34	14	19
Syndecan-1/HGF/MET	-0.038	0.16	0.25	2	-0.39	16	18
regulation of cell adhesion	-0.032	0.14	0.28	10	-0.38	6	16
HPSE	0.033	0.055	0.25	15	-10000	0	15
positive regulation of cell migration	-0.026	0.16	0.26	11	-0.37	12	23
SDC1	-0.028	0.15	0.26	6	-0.37	12	18
Syndecan-1/Collagen	-0.026	0.16	0.26	11	-0.37	12	23
PPIB	0.019	0.004	-10000	0	-10000	0	0
MET	0.012	0.061	-10000	0	-0.55	3	3
PRKACA	0.018	0.005	-10000	0	-10000	0	0
MMP9	0.11	0.12	0.25	100	-0.55	1	101
MAPK1	-0.037	0.13	0.22	2	-0.39	6	8
homophilic cell adhesion	-0.026	0.16	0.26	11	-0.36	12	23
MMP1	0.054	0.14	0.25	54	-0.55	6	60

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	-0.017	0.14	-10000	0	-0.55	16	16
GNB1/GNG2	-0.043	0.073	-10000	0	-0.19	44	44
AKT1	-0.03	0.12	0.32	2	-0.3	13	15
EGF	-0.21	0.28	-10000	0	-0.55	101	101
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.005	0.059	0.24	7	-10000	0	7
mol:Ca2+	-0.039	0.15	0.32	3	-0.32	40	43
LYN	0.004	0.059	0.24	7	-10000	0	7
RhoA/GTP	-0.018	0.061	0.13	2	-0.14	10	12
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.048	0.16	0.31	3	-0.36	45	48
GNG2	0.024	0.036	0.25	6	-10000	0	6
ARRB2	0.018	0.005	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.002	0.066	-10000	0	-0.43	2	2
G beta5/gamma2	-0.054	0.096	-10000	0	-0.26	42	42
PRKCH	-0.049	0.17	0.35	2	-0.36	45	47
DNM1	0.021	0.021	0.25	2	-10000	0	2
TXA2/TP beta/beta Arrestin3	0.008	0.055	-10000	0	-0.55	2	2
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	0.049	0.079	0.25	33	-10000	0	33
G12 family/GTP	-0.052	0.13	-10000	0	-0.31	47	47
ADRBK1	0.019	0.003	-10000	0	-10000	0	0
ADRBK2	0.019	0.004	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0.024	0.007	-10000	0	-10000	0	0
mol:GDP	0.015	0.12	0.41	8	-0.26	3	11
mol:NADP	0.018	0.005	-10000	0	-10000	0	0
RAB11A	0.019	0.003	-10000	0	-10000	0	0
PRKG1	0.028	0.064	0.25	13	-0.55	1	14
mol:IP3	-0.054	0.18	0.37	2	-0.39	45	47
cell morphogenesis	0.024	0.007	-10000	0	-10000	0	0
PLCB2	-0.082	0.24	0.4	2	-0.53	47	49
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	0.018	0.073	0.24	11	-10000	0	11
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.008	0.061	0.24	7	-10000	0	7
RHOA	0.019	0.004	-10000	0	-10000	0	0
PTGIR	0.023	0.033	0.25	5	-10000	0	5
PRKCB1	-0.055	0.18	0.36	2	-0.39	47	49
GNAQ	0.019	0.003	-10000	0	-10000	0	0
mol:L-citrulline	0.018	0.005	-10000	0	-10000	0	0
TXA2/TXA2-R family	-0.083	0.24	0.4	2	-0.54	48	50
LCK	0.018	0.075	0.26	8	-0.26	1	9
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.021	0.032	-10000	0	-10000	0	0
TXA2-R family/G12 family/GDP/G beta/gamma	-0.017	0.13	-10000	0	-0.44	18	18
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.023	0.032	-10000	0	-10000	0	0
MAPK14	-0.028	0.12	0.24	5	-0.24	31	36
TGM2/GTP	-0.068	0.21	0.4	2	-0.46	45	47
MAPK11	-0.031	0.11	0.24	5	-0.24	34	39
ARHGEF1	-0.026	0.083	0.2	3	-0.2	15	18
GNAI2	0.019	0.003	-10000	0	-10000	0	0
JNK cascade	-0.055	0.18	0.34	3	-0.39	48	51
RAB11/GDP	0.017	0.008	-10000	0	-10000	0	0
ICAM1	-0.037	0.13	0.31	3	-0.29	45	48
cAMP biosynthetic process	-0.051	0.17	0.35	2	-0.37	41	43
Gq family/GTP/EBP50	-0.008	0.069	0.24	3	-0.21	23	26
actin cytoskeleton reorganization	0.024	0.007	-10000	0	-10000	0	0
SRC	0.002	0.054	0.23	6	-10000	0	6
GNB5	0.019	0.004	-10000	0	-10000	0	0
GNB1	0.018	0.006	-10000	0	-10000	0	0
EGF/EGFR	-0.019	0.093	0.28	7	-0.32	2	9
VCAM1	-0.048	0.16	0.29	3	-0.34	48	51
TP beta/Gq family/GDP/G beta5/gamma2	0.002	0.066	-10000	0	-0.43	2	2
platelet activation	-0.038	0.15	0.3	4	-0.31	39	43
PGI2/IP	0.017	0.023	0.18	5	-10000	0	5
PRKACA	0.019	0.028	-10000	0	-10000	0	0
Gq family/GDP/G beta5/gamma2	0.001	0.062	-10000	0	-0.36	2	2
TXA2/TP beta/beta Arrestin2	0.005	0.045	-10000	0	-0.33	1	1
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.002	0.029	-10000	0	-10000	0	0
mol:DAG	-0.063	0.2	0.38	2	-0.44	46	48
EGFR	0.016	0.039	0.25	1	-0.55	1	2
TXA2/TP alpha	-0.074	0.23	0.4	2	-0.5	46	48
Gq family/GTP	-0.012	0.064	0.22	1	-0.23	18	19
YES1	0.004	0.058	0.25	7	-10000	0	7
GNAI2/GTP	0.01	0.029	-10000	0	-10000	0	0
PGD2/DP	0.034	0.054	0.18	33	-10000	0	33
SLC9A3R1	0.01	0.071	-10000	0	-0.55	4	4
FYN	0.005	0.059	0.24	7	-10000	0	7
mol:NO	0.018	0.005	-10000	0	-10000	0	0
GNA15	0.024	0.033	0.25	5	-10000	0	5
PGK/cGMP	0.027	0.039	-10000	0	-0.35	1	1
RhoA/GDP	0.017	0.008	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0.02	0.085	-10000	0	-0.28	13	13
NOS3	0.018	0.005	-10000	0	-10000	0	0
RAC1	0.018	0.006	-10000	0	-10000	0	0
PRKCA	-0.05	0.16	0.32	3	-0.36	42	45
PRKCB	-0.053	0.17	0.35	2	-0.38	48	50
PRKCE	-0.05	0.17	0.32	3	-0.37	45	48
PRKCD	-0.057	0.18	0.35	2	-0.4	48	50
PRKCG	-0.055	0.18	0.33	3	-0.4	47	50
muscle contraction	-0.076	0.22	0.38	2	-0.5	47	49
PRKCZ	-0.062	0.17	0.41	2	-0.37	47	49
ARR3	-0.016	0.003	-10000	0	-10000	0	0
TXA2/TP beta	0.025	0.042	-10000	0	-10000	0	0
PRKCQ	-0.055	0.18	0.35	2	-0.38	47	49
MAPKKK cascade	-0.07	0.21	0.37	2	-0.47	45	47
SELE	-0.056	0.17	0.29	4	-0.39	48	52
TP beta/GNAI2/GDP/G beta/gamma	0.039	0.044	-10000	0	-10000	0	0
ROCK1	0.019	0.004	-10000	0	-10000	0	0
GNA14	-0.017	0.14	-10000	0	-0.55	16	16
chemotaxis	-0.099	0.27	0.41	2	-0.62	48	50
GNA12	0.018	0.005	-10000	0	-10000	0	0
GNA13	0.019	0.004	-10000	0	-10000	0	0
GNA11	0.017	0.036	-10000	0	-0.55	1	1
Rac1/GTP	0.013	0.004	-10000	0	-10000	0	0

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.019	0.004	-10000	0	-10000	0	0
VLDLR	-0.013	0.13	-10000	0	-0.55	14	14
LRPAP1	0.019	0.004	-10000	0	-10000	0	0
NUDC	0.019	0.004	-10000	0	-10000	0	0
RELN/LRP8	-0.042	0.17	0.33	2	-0.35	55	57
CaM/Ca2+	0.014	0.003	-10000	0	-10000	0	0
KATNA1	0.018	0.005	-10000	0	-10000	0	0
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	-0.065	0.15	0.22	2	-0.32	55	57
IQGAP1/CaM	0.026	0.008	-10000	0	-10000	0	0
DAB1	0.035	0.078	0.25	28	-10000	0	28
IQGAP1	0.019	0.004	-10000	0	-10000	0	0
PLA2G7	0.097	0.11	0.25	85	-10000	0	85
CALM1	0.018	0.004	-10000	0	-10000	0	0
DYNLT1	0.018	0.004	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	0.035	0.037	0.19	13	-10000	0	13
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0.018	0.004	-10000	0	-10000	0	0
CDK5R1	0.026	0.039	0.25	7	-10000	0	7
LIS1/Poliovirus Protein 3A	-0.011	0.004	-10000	0	-10000	0	0
CDK5R2	0.047	0.094	0.25	42	-10000	0	42
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.057	0.19	0.33	3	-0.38	61	64
YWHAE	0.018	0.005	-10000	0	-10000	0	0
NDEL1/14-3-3 E	-0.036	0.14	0.3	8	-0.33	3	11
MAP1B	0.003	0.001	-10000	0	-10000	0	0
RAC1	0.005	0.002	-10000	0	-10000	0	0
p35/CDK5	-0.06	0.13	0.23	1	-0.3	48	49
RELN	-0.11	0.24	0.25	4	-0.55	57	61
PAFAH/LIS1	0.049	0.093	0.18	83	-10000	0	83
LIS1/CLIP170	-0.015	0.006	-10000	0	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.053	0.098	-10000	0	-0.29	1	1
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.064	0.14	-10000	0	-0.3	57	57
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	-0.043	0.14	0.29	6	-0.29	41	47
LIS1/IQGAP1	-0.015	0.006	-10000	0	-10000	0	0
RHOA	0.005	0.002	-10000	0	-10000	0	0
PAFAH1B1	-0.013	0.005	-10000	0	-10000	0	0
PAFAH1B3	0.018	0.004	-10000	0	-10000	0	0
PAFAH1B2	0.018	0.005	-10000	0	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0.012	0.024	-10000	0	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.04	0.13	0.29	7	-0.33	3	10
LRP8	0.031	0.052	0.25	13	-10000	0	13
NDEL1/Katanin 60	-0.038	0.13	0.3	8	-0.33	3	11
P39/CDK5	-0.038	0.16	0.29	12	-0.3	47	59
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	-0.015	0.006	-10000	0	-10000	0	0
CDK5	-0.065	0.13	0.24	1	-0.3	54	55
PPP2R5D	0.018	0.005	-10000	0	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.013	0.005	-10000	0	-10000	0	0
CSNK2A1	0.018	0.005	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.049	0.17	0.32	3	-0.33	59	62
RELN/VLDLR	-0.05	0.18	0.33	2	-0.35	60	62
CDC42	0.005	0.002	-10000	0	-10000	0	0

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	0.041	0.071	0.25	25	-10000	0	25
GNB1/GNG2	0.021	0.13	0.31	2	-0.34	5	7
mol:DAG	-0.004	0.11	0.22	7	-0.32	5	12
PLCG1	-0.005	0.11	0.23	7	-0.33	5	12
YES1	-0.002	0.12	0.24	6	-0.27	25	31
FZD3	-0.028	0.16	0.25	1	-0.55	21	22
FZD6	0.009	0.071	-10000	0	-0.55	4	4
G protein	0.029	0.13	0.28	13	-0.34	5	18
MAP3K7	-0.033	0.12	0.24	2	-0.41	11	13
mol:Ca2+	-0.004	0.11	0.21	10	-0.31	5	15
mol:IP3	-0.004	0.11	0.22	7	-0.32	5	12
NLK	0.006	0.045	-10000	0	-0.69	1	1
GNB1	0.018	0.006	-10000	0	-10000	0	0
CAMK2A	-0.033	0.14	0.24	3	-0.4	15	18
MAP3K7IP1	0	0	-10000	0	-10000	0	0
Noncanonical Wnts/FZD	0.004	0.13	0.25	6	-0.28	27	33
CSNK1A1	0.019	0.003	-10000	0	-10000	0	0
GNAS	0.006	0.13	0.27	15	-0.27	25	40
GO:0007205	-0.006	0.11	0.23	5	-0.33	5	10
WNT6	0.024	0.042	0.25	8	-10000	0	8
WNT4	-0.007	0.15	0.25	12	-0.55	16	28
NFAT1/CK1 alpha	0.027	0.13	0.32	7	-0.34	5	12
GNG2	0.024	0.036	0.25	6	-10000	0	6
WNT5A	0.08	0.1	0.25	66	-10000	0	66
WNT11	0.069	0.097	0.25	55	-10000	0	55
CDC42	-0.009	0.11	0.23	7	-0.34	5	12

×

Endothelins

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
AKT1	0.043	0.13	0.25	43	-0.35	5	48
PTK2B	0.019	0.004	-10000	0	-10000	0	0
mol:Ca2+	0.003	0.18	0.44	5	-0.6	8	13
EDN1	0.036	0.13	0.28	9	-0.5	8	17
EDN3	0.023	0.085	0.25	25	-0.55	1	26
EDN2	0.011	0.041	0.25	6	-10000	0	6
HRAS/GDP	0.006	0.13	0.3	6	-0.36	8	14
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	0.013	0.1	0.22	10	-0.33	5	15
ADCY4	0.021	0.12	0.25	10	-0.36	10	20
ADCY5	-0.078	0.19	0.24	7	-0.36	61	68
ADCY6	0.022	0.12	0.25	11	-0.36	10	21
ADCY7	0.021	0.12	0.25	9	-0.36	10	19
ADCY1	0.036	0.13	0.27	19	-0.36	10	29
ADCY2	0.008	0.15	0.25	15	-0.35	19	34
ADCY3	0.024	0.12	0.25	11	-0.34	10	21
ADCY8	0.002	0.15	0.25	15	-0.32	26	41
ADCY9	0.022	0.12	0.24	10	-0.36	10	20
arachidonic acid secretion	-0.015	0.16	0.33	8	-0.41	19	27
ETB receptor/Endothelin-1/Gq/GTP	-0.002	0.11	0.22	2	-0.29	19	21
GNAO1	-0.05	0.19	0.25	1	-0.55	31	32
HRAS	0.018	0.007	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	0.063	0.14	0.32	35	-0.34	4	39
ETA receptor/Endothelin-1/Gs/GTP	0.052	0.15	0.3	37	-0.36	11	48
mol:GTP	0	0.004	-10000	0	-10000	0	0
COL3A1	0.083	0.18	0.38	56	-0.43	5	61
EDNRB	0.029	0.051	-10000	0	-0.36	2	2
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	0.044	0.14	0.34	18	-0.37	4	22
CYSLTR1	0.045	0.13	0.34	9	-0.37	4	13
SLC9A1	0.029	0.079	0.23	8	-0.23	4	12
mol:GDP	0.002	0.13	0.3	8	-0.38	8	16
SLC9A3	-0.41	0.3	-10000	0	-0.62	148	148
RAF1	-0.008	0.14	0.35	4	-0.4	9	13
JUN	0.013	0.17	0.61	2	-0.57	2	4
JAK2	0.04	0.12	0.3	11	-0.38	3	14
mol:IP3	0.005	0.1	0.23	3	-0.32	11	14
ETA receptor/Endothelin-1	0.07	0.16	0.37	38	-0.38	7	45
PLCB1	0.016	0.01	-10000	0	-10000	0	0
PLCB2	0.02	0.031	0.25	4	-10000	0	4
ETA receptor/Endothelin-3	0.054	0.081	0.31	8	-0.4	1	9
FOS	-0.043	0.26	0.42	3	-0.95	16	19
Gai/GDP	-0.14	0.3	-10000	0	-0.68	57	57
CRK	0.018	0.005	-10000	0	-10000	0	0
mol:Ca ++	0.016	0.14	0.28	11	-0.45	7	18
BCAR1	0.018	0.005	-10000	0	-10000	0	0
PRKCB1	0.003	0.1	0.24	2	-0.31	11	13
GNAQ	0.017	0.012	-10000	0	-10000	0	0
GNAZ	-0.017	0.14	-10000	0	-0.55	16	16
GNAL	-0.001	0.11	0.25	3	-0.55	10	13
Gs family/GDP	-0.002	0.14	0.28	7	-0.4	11	18
ETA receptor/Endothelin-1/Gq/GTP	0.012	0.11	0.25	7	-0.31	14	21
MAPK14	-0.003	0.088	0.26	2	-0.3	7	9
TRPC6	0.002	0.19	0.45	5	-0.66	7	12
GNAI2	0.019	0.003	-10000	0	-10000	0	0
GNAI3	0.019	0.003	-10000	0	-10000	0	0
GNAI1	0.009	0.071	-10000	0	-0.55	4	4
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.001	0.095	0.19	2	-0.3	9	11
ETB receptor/Endothelin-2	0.037	0.045	-10000	0	-0.4	1	1
ETB receptor/Endothelin-3	0.043	0.066	0.25	6	-0.36	2	8
ETB receptor/Endothelin-1	0.048	0.12	0.26	28	-0.38	8	36
MAPK3	-0.032	0.22	0.37	5	-0.73	16	21
MAPK1	-0.032	0.22	0.37	5	-0.72	17	22
Rac1/GDP	0.005	0.12	0.28	6	-0.36	7	13
cAMP biosynthetic process	-0.038	0.16	0.26	7	-0.42	16	23
MAPK8	0	0.18	0.38	6	-0.52	15	21
SRC	0.019	0.004	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.042	0.14	0.19	1	-0.32	32	33
p130Cas/CRK/Src/PYK2	0.002	0.14	0.36	8	-0.44	6	14
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	0.005	0.13	0.3	6	-0.36	8	14
COL1A2	0.076	0.19	0.4	44	-0.53	5	49
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	0.046	0.063	-10000	0	-10000	0	0
mol:DAG	0.005	0.1	0.23	3	-0.32	11	14
MAP2K2	-0.02	0.17	0.38	5	-0.49	18	23
MAP2K1	-0.018	0.17	0.34	7	-0.49	18	25
EDNRA	0.046	0.08	0.29	6	-10000	0	6
positive regulation of muscle contraction	0.038	0.12	0.3	17	-0.33	4	21
Gq family/GDP	-0.012	0.12	-10000	0	-0.39	10	10
HRAS/GTP	-0.002	0.13	0.29	6	-0.39	7	13
PRKCH	0.003	0.1	0.23	2	-0.36	5	7
RAC1	0.018	0.006	-10000	0	-10000	0	0
PRKCA	0.004	0.11	0.26	4	-0.35	6	10
PRKCB	0.001	0.11	0.23	2	-0.37	6	8
PRKCE	0.003	0.1	0.23	2	-0.36	5	7
PRKCD	0	0.1	0.23	2	-0.32	9	11
PRKCG	0.006	0.1	0.23	3	-0.34	5	8
regulation of vascular smooth muscle contraction	-0.055	0.3	0.45	3	-1.1	16	19
PRKCQ	-0.003	0.11	0.27	3	-0.37	7	10
PLA2G4A	-0.018	0.17	0.34	8	-0.44	19	27
GNA14	-0.018	0.14	-10000	0	-0.55	16	16
GNA15	0.022	0.035	0.25	5	-10000	0	5
GNA12	0.018	0.005	-10000	0	-10000	0	0
GNA11	0.015	0.037	-10000	0	-0.55	1	1
Rac1/GTP	0.062	0.13	0.32	35	-0.34	4	39
MMP1	0.002	0.19	0.43	5	-0.9	6	11

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	0.026	0.009	-10000	0	-10000	0	0
alphaV beta3 Integrin	0.023	0.076	-10000	0	-0.35	10	10
PTK2	-0.086	0.15	0.35	3	-0.49	9	12
IGF1R	0.014	0.05	-10000	0	-0.55	2	2
PI4KB	0.018	0.005	-10000	0	-10000	0	0
MFGE8	0.019	0.004	-10000	0	-10000	0	0
SRC	0.019	0.004	-10000	0	-10000	0	0
CDKN1B	-0.11	0.22	-10000	0	-0.5	58	58
VEGFA	0.018	0.005	-10000	0	-10000	0	0
ILK	-0.11	0.22	-10000	0	-0.5	57	57
ROCK1	0.019	0.004	-10000	0	-10000	0	0
AKT1	-0.11	0.2	-10000	0	-0.47	55	55
PTK2B	-0.013	0.067	0.35	1	-0.31	5	6
alphaV/beta3 Integrin/JAM-A	-0.05	0.16	-10000	0	-0.33	57	57
CBL	0.018	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.11	0.18	-10000	0	-0.35	92	92
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.039	0.064	0.33	1	-0.42	3	4
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.053	0.11	-10000	0	-0.36	9	9
alphaV/beta3 Integrin/Syndecan-1	0.026	0.07	-10000	0	-0.35	8	8
PI4KA	0.018	0.005	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.033	0.098	-10000	0	-0.39	8	8
PI4 Kinase	0.025	0.01	-10000	0	-10000	0	0
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.04	0.16	-10000	0	-0.36	49	49
RPS6KB1	-0.006	0.11	0.38	3	-0.64	2	5
TLN1	0.018	0.005	-10000	0	-10000	0	0
MAPK3	-0.049	0.14	-10000	0	-0.6	11	11
GPR124	0.019	0.004	-10000	0	-10000	0	0
MAPK1	-0.048	0.14	-10000	0	-0.6	11	11
PXN	0.019	0.004	-10000	0	-10000	0	0
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
alphaV/beta3 Integrin/Tumstatin	-0.17	0.2	-10000	0	-0.36	125	125
cell adhesion	-0.09	0.16	-10000	0	-0.3	88	88
ANGPTL3	-0.2	0.26	-10000	0	-0.55	88	88
VEGFR2 homodimer/VEGFA homodimer/Src	0.034	0.013	-10000	0	-10000	0	0
IGF-1R heterotetramer	0.014	0.05	-10000	0	-0.55	2	2
Rac1/GDP	0.013	0.004	-10000	0	-10000	0	0
TGFBR2	0.019	0.003	-10000	0	-10000	0	0
ITGB3	0.008	0.079	-10000	0	-0.55	5	5
IGF1	0.019	0.075	0.25	8	-0.55	3	11
RAC1	0.018	0.006	-10000	0	-10000	0	0
regulation of cell-matrix adhesion	0.029	0.055	-10000	0	-0.35	5	5
apoptosis	0.019	0.003	-10000	0	-10000	0	0
CD47	0.019	0.002	-10000	0	-10000	0	0
alphaV/beta3 Integrin/CD47	0.031	0.054	-10000	0	-0.35	5	5
VCL	0.018	0.005	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Del1	0.095	0.11	-10000	0	-0.39	7	7
CSF1	0.024	0.033	0.25	5	-10000	0	5
PIK3C2A	-0.11	0.22	-10000	0	-0.5	57	57
PI4 Kinase/Pyk2	-0.085	0.11	-10000	0	-0.31	41	41
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.037	0.054	-10000	0	-0.32	5	5
FAK1/Vinculin	-0.07	0.13	0.33	3	-0.4	8	11
alphaV beta3/Integrin/ppsTEM5	0.029	0.055	-10000	0	-0.35	5	5
RHOA	0.019	0.004	-10000	0	-10000	0	0
VTN	-0.11	0.24	0.25	1	-0.55	57	58
BCAR1	0.018	0.005	-10000	0	-10000	0	0
FGF2	0.008	0.079	-10000	0	-0.55	5	5
F11R	-0.021	0.055	-10000	0	-0.41	5	5
alphaV/beta3 Integrin/Lactadherin	0.029	0.055	-10000	0	-0.35	5	5
alphaV/beta3 Integrin/TGFBR2	0.03	0.054	-10000	0	-0.35	5	5
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.046	0.027	-10000	0	-10000	0	0
HSP90AA1	0.019	0.004	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	0.027	0.05	-10000	0	-0.32	5	5
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.063	0.092	0.25	48	-10000	0	48
alphaV/beta3 Integrin/Pyk2	0.018	0.048	-10000	0	-0.31	5	5
SDC1	0.014	0.065	0.25	2	-0.55	3	5
VAV3	-0.018	0.034	-10000	0	-0.31	1	1
PTPN11	0.018	0.004	-10000	0	-10000	0	0
IRS1	0.019	0.016	0.25	1	-10000	0	1
FAK1/Paxillin	-0.071	0.13	0.33	3	-0.4	8	11
cell migration	-0.068	0.12	0.32	3	-0.38	7	10
ITGAV	0.019	0.003	-10000	0	-10000	0	0
PI3K	-0.041	0.15	-10000	0	-0.31	56	56
SPP1	-0.083	0.22	-10000	0	-0.55	46	46
KDR	0.019	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.019	0.003	-10000	0	-10000	0	0
COL4A3	-0.27	0.28	-10000	0	-0.55	127	127
angiogenesis	-0.059	0.17	-10000	0	-0.62	11	11
Rac1/GTP	-0.019	0.03	-10000	0	-0.29	1	1
EDIL3	0.13	0.14	0.25	126	-0.55	3	129
cell proliferation	0.03	0.054	-10000	0	-0.35	5	5

×

Calcium signaling in the CD4+ TCR pathway

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
NFATC1	0.02	0.056	0.18	10	-10000	0	10
NFATC2	0.031	0.072	0.19	29	-10000	0	29
NFATC3	0.019	0.057	0.19	9	-10000	0	9
CD40LG	0.068	0.24	0.52	31	-0.47	6	37
PTGS2	0.008	0.29	0.49	28	-0.53	36	64
JUNB	0.018	0.004	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0.021	0.035	0.14	2	-10000	0	2
CaM/Ca2+	0.021	0.035	0.14	2	-10000	0	2
CALM1	0.018	0.026	-10000	0	-10000	0	0
JUN	0.017	0.026	-10000	0	-10000	0	0
mol:Ca2+	0.005	0.017	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.013	0.016	-10000	0	-10000	0	0
FOSL1	0.036	0.062	0.25	19	-10000	0	19
CREM	0.019	0.004	-10000	0	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	0.069	0.17	0.38	39	-10000	0	39
FOS	-0.002	0.11	-10000	0	-0.55	10	10
IFNG	0.08	0.26	0.54	43	-0.47	6	49
AP-1/NFAT1-c-4	0.091	0.28	0.58	40	-0.52	7	47
FASLG	0.077	0.26	0.55	41	-0.47	6	47
NFAT1-c-4/ICER1	0.054	0.11	0.31	26	-10000	0	26
IL2RA	0.075	0.26	0.51	41	-0.54	9	50
FKBP12/FK506	0.014	0.003	-10000	0	-10000	0	0
CSF2	0.064	0.23	0.48	31	-0.47	6	37
JunB/Fra1/NFAT1-c-4	0.068	0.12	0.31	32	-10000	0	32
IL4	0.059	0.22	0.48	29	-0.47	6	35
IL2	0	0.077	-10000	0	-0.86	2	2
IL3	-0.003	0.08	-10000	0	-0.66	3	3
FKBP1A	0.018	0.004	-10000	0	-10000	0	0
BATF3	0.017	0.036	-10000	0	-0.55	1	1
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.019	0.016	0.25	1	-10000	0	1

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.013	0.19	0.31	8	-0.33	58	66
SMAD6-7/SMURF1	0.036	0.012	-10000	0	-10000	0	0
NOG	0.044	0.082	0.25	33	-10000	0	33
SMAD9	-0.042	0.17	-10000	0	-0.45	33	33
SMAD4	0.019	0.003	-10000	0	-10000	0	0
SMAD5	-0.015	0.095	0.23	1	-0.38	4	5
BMP7/USAG1	-0.18	0.28	0.36	4	-0.44	124	128
SMAD5/SKI	-0.003	0.1	0.27	1	-0.39	5	6
SMAD1	0.014	0.069	-10000	0	-0.46	1	1
BMP2	0.011	0.061	-10000	0	-0.55	3	3
SMAD1/SMAD1/SMAD4	0.01	0.064	-10000	0	-0.37	2	2
BMPR1A	0.018	0.005	-10000	0	-10000	0	0
BMPR1B	-0.015	0.16	0.25	10	-0.55	19	29
BMPR1A-1B/BAMBI	-0.049	0.17	-10000	0	-0.37	54	54
AHSG	0	0.04	0.25	5	-10000	0	5
CER1	-0.001	0.028	0.25	2	-10000	0	2
BMP2-4/CER1	0.029	0.055	-10000	0	-0.35	4	4
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.008	0.091	-10000	0	-0.32	5	5
BMP2-4 (homodimer)	0.021	0.058	0.19	4	-0.41	4	8
RGMB	0.02	0.015	0.25	1	-10000	0	1
BMP6/BMPR2/BMPR1A-1B	0.02	0.1	-10000	0	-0.32	19	19
RGMA	0.019	0.074	0.25	8	-0.55	3	11
SMURF1	0.018	0.004	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.009	0.089	0.23	2	-0.35	3	5
BMP2-4/USAG1	-0.12	0.2	-10000	0	-0.36	97	97
SMAD6/SMURF1/SMAD5	-0.008	0.1	-10000	0	-0.39	5	5
SOSTDC1	-0.21	0.28	0.25	6	-0.55	100	106
BMP7/BMPR2/BMPR1A-1B	-0.027	0.18	0.33	1	-0.33	60	61
SKI	0.018	0.006	-10000	0	-10000	0	0
BMP6 (homodimer)	0.02	0.021	0.25	2	-10000	0	2
HFE2	0.025	0.067	0.25	19	-10000	0	19
ZFYVE16	0.019	0.002	-10000	0	-10000	0	0
MAP3K7	0.019	0.004	-10000	0	-10000	0	0
BMP2-4/CHRD	0.019	0.09	-10000	0	-0.38	11	11
SMAD5/SMAD5/SMAD4	-0.005	0.11	0.27	1	-0.39	5	6
MAPK1	0.018	0.005	-10000	0	-10000	0	0
TAK1/TAB family	0	0.084	-10000	0	-0.36	2	2
BMP7 (homodimer)	-0.051	0.24	0.25	36	-0.55	45	81
NUP214	0.019	0.003	-10000	0	-10000	0	0
BMP6/FETUA	0.029	0.028	-10000	0	-10000	0	0
SMAD1/SKI	0.024	0.075	-10000	0	-0.41	2	2
SMAD6	0.019	0.004	-10000	0	-10000	0	0
CTDSP2	0.015	0.008	-10000	0	-10000	0	0
BMP2-4/FETUA	0.031	0.057	-10000	0	-0.35	4	4
MAP3K7IP1	0	0	-10000	0	-10000	0	0
GREM1	0.057	0.21	0.25	93	-0.55	21	114
BMPR2 (homodimer)	0.019	0.003	-10000	0	-10000	0	0
GADD34/PP1CA	0.037	0.01	-10000	0	-10000	0	0
BMPR1A-1B (homodimer)	-0.001	0.12	-10000	0	-0.39	20	20
CHRDL1	-0.047	0.2	0.25	8	-0.55	33	41
ENDOFIN/SMAD1	0.022	0.078	-10000	0	-0.41	2	2
SMAD6-7/SMURF1/SMAD1	0.031	0.079	-10000	0	-0.39	2	2
SMAD6/SMURF1	0.018	0.004	-10000	0	-10000	0	0
BAMBI	-0.066	0.2	-10000	0	-0.55	38	38
SMURF2	0.019	0.004	-10000	0	-10000	0	0
BMP2-4/CHRDL1	-0.015	0.14	-10000	0	-0.35	35	35
BMP2-4/GREM1	0.048	0.14	0.33	1	-0.35	23	24
SMAD7	0.019	0.003	-10000	0	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.037	0.17	-10000	0	-0.45	34	34
SMAD1/SMAD6	0.021	0.077	-10000	0	-0.41	2	2
TAK1/SMAD6	0.026	0.008	-10000	0	-10000	0	0
BMP7	-0.051	0.24	0.25	36	-0.55	45	81
BMP6	0.02	0.021	0.25	2	-10000	0	2
MAP3K7IP2	0	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.01	0.077	0.18	1	-0.32	3	4
PPM1A	0.019	0.004	-10000	0	-10000	0	0
SMAD1/SMURF2	0.022	0.078	-10000	0	-0.4	2	2
SMAD7/SMURF1	0.027	0.007	-10000	0	-10000	0	0
CTDSPL	0.019	0.003	-10000	0	-10000	0	0
PPP1CA	0.019	0.003	-10000	0	-10000	0	0
XIAP	0.019	0.002	-10000	0	-10000	0	0
CTDSP1	0.018	0.004	-10000	0	-10000	0	0
PPP1R15A	0.019	0.004	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.004	0.096	0.2	1	-0.36	4	5
CHRD	0.002	0.1	0.25	1	-0.55	8	9
BMPR2	0.019	0.003	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.012	0.084	0.2	2	-0.35	2	4
BMP4	0.02	0.046	0.25	4	-0.55	1	5
FST	0.039	0.089	0.25	27	-0.55	2	29
BMP2-4/NOG	0.048	0.077	0.33	4	-0.33	4	8
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.024	0.18	0.32	1	-0.32	59	60

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.019	0.003	-10000	0	-10000	0	0
LAT2	-0.045	0.12	-10000	0	-0.36	17	17
AP1	-0.029	0.15	-10000	0	-0.45	12	12
mol:PIP3	-0.03	0.18	0.37	8	-0.42	18	26
IKBKB	-0.005	0.12	0.27	16	-0.26	13	29
AKT1	-0.043	0.16	0.33	15	-0.33	27	42
IKBKG	-0.006	0.12	0.26	17	-0.26	13	30
MS4A2	-0.032	0.16	0.25	5	-0.54	21	26
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.018	0.006	-10000	0	-10000	0	0
MAP3K1	-0.022	0.13	0.29	7	-0.38	11	18
mol:Ca2+	-0.018	0.14	0.31	10	-0.32	18	28
LYN	0.013	0.017	-10000	0	-10000	0	0
CBLB	-0.048	0.12	-10000	0	-0.36	18	18
SHC1	0.018	0.004	-10000	0	-10000	0	0
RasGAP/p62DOK	0.035	0.01	-10000	0	-10000	0	0
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	0.021	0.03	0.25	4	-10000	0	4
PLD2	-0.049	0.16	0.32	14	-0.34	41	55
PTPN13	-0.049	0.17	-10000	0	-0.53	16	16
PTPN11	0.01	0.022	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	-0.022	0.14	0.34	11	-0.36	11	22
SYK	0.008	0.053	-10000	0	-0.56	2	2
GRB2	0.019	0.003	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.048	0.15	-10000	0	-0.36	36	36
LAT	-0.045	0.12	-10000	0	-0.36	19	19
PAK2	-0.025	0.14	0.32	5	-0.42	11	16
NFATC2	-0.002	0.065	0.25	2	-0.17	1	3
HRAS	-0.03	0.14	0.35	2	-0.39	17	19
GAB2	0.018	0.004	-10000	0	-10000	0	0
PLA2G1B	0.005	0.12	-10000	0	-0.88	4	4
Fc epsilon R1	-0.043	0.18	-10000	0	-0.4	50	50
Antigen/IgE/Fc epsilon R1	-0.037	0.17	-10000	0	-0.36	50	50
mol:GDP	-0.03	0.14	0.28	2	-0.45	11	13
JUN	0.018	0.006	-10000	0	-10000	0	0
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.019	0.016	0.26	1	-10000	0	1
FOS	-0.004	0.11	-10000	0	-0.55	10	10
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.041	0.12	-10000	0	-0.29	37	37
CHUK	-0.008	0.12	0.26	14	-0.26	13	27
KLRG1	-0.044	0.11	-10000	0	-0.27	39	39
VAV1	-0.044	0.12	-10000	0	-0.37	19	19
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.047	0.12	-10000	0	-0.36	19	19
negative regulation of mast cell degranulation	-0.029	0.11	-10000	0	-0.35	10	10
BTK	-0.034	0.13	-10000	0	-0.45	10	10
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.064	0.17	-10000	0	-0.36	48	48
GAB2/PI3K/SHP2	-0.077	0.12	-10000	0	-0.33	40	40
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.047	0.13	-10000	0	-0.29	48	48
RAF1	0.006	0.12	-10000	0	-0.96	4	4
Fc epsilon R1/FcgammaRIIB/SHIP	-0.028	0.18	-10000	0	-0.35	53	53
FCER1G	0.019	0.043	0.25	7	-10000	0	7
FCER1A	-0.073	0.21	-10000	0	-0.56	39	39
Antigen/IgE/Fc epsilon R1/Fyn	-0.026	0.16	-10000	0	-0.34	46	46
MAPK3	0.003	0.12	-10000	0	-0.88	4	4
MAPK1	0.004	0.12	-10000	0	-0.91	4	4
NFKB1	0.019	0.001	-10000	0	-10000	0	0
MAPK8	-0.021	0.16	-10000	0	-0.63	14	14
DUSP1	0.019	0.004	-10000	0	-10000	0	0
NF-kappa-B/RelA	-0.013	0.066	0.13	3	-0.19	6	9
actin cytoskeleton reorganization	-0.035	0.16	-10000	0	-0.58	12	12
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.02	0.14	0.4	2	-0.44	11	13
FER	-0.048	0.11	-10000	0	-0.35	19	19
RELA	0.019	0.003	-10000	0	-10000	0	0
ITK	0.001	0.054	0.14	3	-0.25	3	6
SOS1	0.019	0.004	-10000	0	-10000	0	0
PLCG1	-0.021	0.15	0.34	4	-0.39	18	22
cytokine secretion	-0.015	0.042	-10000	0	-10000	0	0
SPHK1	-0.029	0.12	0.2	1	-0.35	17	18
PTK2	-0.037	0.17	-10000	0	-0.61	12	12
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.045	0.16	-10000	0	-0.37	39	39
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	-0.027	0.18	0.37	9	-0.41	18	27
MAP2K2	0.002	0.12	-10000	0	-0.9	4	4
MAP2K1	0.004	0.12	-10000	0	-0.9	4	4
MAP2K7	0.018	0.004	-10000	0	-10000	0	0
KLRG1/SHP2	-0.034	0.11	-10000	0	-0.33	13	13
MAP2K4	0.007	0.11	-10000	0	-0.86	4	4
Fc epsilon R1/FcgammaRIIB	-0.035	0.19	-10000	0	-0.37	53	53
mol:Choline	-0.048	0.16	0.31	14	-0.33	41	55
SHC/Grb2/SOS1	-0.015	0.13	-10000	0	-0.41	10	10
FYN	0.018	0.005	-10000	0	-10000	0	0
DOK1	0.019	0.004	-10000	0	-10000	0	0
PXN	-0.033	0.16	0.37	1	-0.56	12	13
HCLS1	-0.046	0.12	-10000	0	-0.36	18	18
PRKCB	-0.015	0.15	0.3	14	-0.34	18	32
FCGR2B	0.007	0.089	0.25	2	-0.55	6	8
IGHE	-0.001	0.007	-10000	0	-10000	0	0
KLRG1/SHIP	-0.03	0.11	-10000	0	-0.36	10	10
LCP2	0.021	0.026	0.25	3	-10000	0	3
PLA2G4A	-0.06	0.14	-10000	0	-0.38	28	28
RASA1	0.019	0.002	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.048	0.16	0.31	14	-0.33	41	55
IKK complex	0	0.1	0.24	17	-0.23	6	23
WIPF1	0.019	0.003	-10000	0	-10000	0	0

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.028	0.17	0.26	5	-0.56	22	27
PDGF/PDGFRA/CRKL	-0.008	0.12	0.19	2	-0.4	20	22
positive regulation of JUN kinase activity	0.012	0.1	-10000	0	-0.31	20	20
CRKL	0.018	0.005	-10000	0	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.003	0.13	0.19	14	-0.4	22	36
AP1	-0.073	0.23	-10000	0	-0.9	16	16
mol:IP3	-0.043	0.12	0.15	5	-0.41	22	27
PLCG1	-0.043	0.12	0.15	5	-0.41	22	27
PDGF/PDGFRA/alphaV Integrin	-0.008	0.12	0.19	2	-0.4	22	24
RAPGEF1	0.019	0.004	-10000	0	-10000	0	0
CRK	0.018	0.005	-10000	0	-10000	0	0
mol:Ca2+	-0.043	0.12	0.15	5	-0.41	22	27
CAV3	0.015	0.064	0.25	16	-10000	0	16
CAV1	0.016	0.036	-10000	0	-0.55	1	1
SHC/Grb2/SOS1	0.013	0.1	-10000	0	-0.31	20	20
PDGF/PDGFRA/Shf	-0.008	0.12	0.19	5	-0.39	22	27
FOS	-0.071	0.23	0.31	2	-0.88	16	18
JUN	-0.018	0.024	-10000	0	-10000	0	0
oligodendrocyte development	-0.008	0.12	0.19	2	-0.4	22	24
GRB2	0.019	0.003	-10000	0	-10000	0	0
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
mol:DAG	-0.043	0.12	0.15	5	-0.41	22	27
PDGF/PDGFRA	-0.028	0.17	0.26	5	-0.55	22	27
actin cytoskeleton reorganization	-0.011	0.12	-10000	0	-0.4	22	22
SRF	-0.011	0.013	-10000	0	-10000	0	0
SHC1	0.018	0.004	-10000	0	-10000	0	0
PI3K	0.004	0.11	-10000	0	-0.34	22	22
PDGF/PDGFRA/Crk/C3G	0.002	0.11	-10000	0	-0.34	22	22
JAK1	-0.04	0.11	0.14	4	-0.4	21	25
ELK1/SRF	-0.029	0.1	0.3	2	-0.32	20	22
SHB	0.018	0.005	-10000	0	-10000	0	0
SHF	0.019	0.004	-10000	0	-10000	0	0
CSNK2A1	0.016	0.022	-10000	0	-10000	0	0
GO:0007205	-0.04	0.13	0.29	3	-0.43	22	25
SOS1	0.019	0.004	-10000	0	-10000	0	0
Ras protein signal transduction	0.012	0.1	-10000	0	-0.31	20	20
PDGF/PDGFRA/SHB	-0.011	0.12	-10000	0	-0.4	22	22
PDGF/PDGFRA/Caveolin-1	-0.008	0.12	0.19	5	-0.4	21	26
ITGAV	0.019	0.003	-10000	0	-10000	0	0
ELK1	-0.04	0.11	0.34	1	-0.38	21	22
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
PDGF/PDGFRA/Crk	-0.01	0.12	0.19	4	-0.4	22	26
JAK-STAT cascade	-0.04	0.11	0.14	4	-0.4	21	25
cell proliferation	-0.008	0.12	0.19	5	-0.39	22	27

×

Effects of Botulinum toxin

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
STX1A	-0.003	0.025	0.14	7	-10000	0	7
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.038	0.044	-10000	0	-10000	0	0
STXBP1	0.019	0.003	-10000	0	-10000	0	0
ACh/CHRNA1	0.075	0.091	0.2	82	-10000	0	82
RAB3GAP2/RIMS1/UNC13B	0.045	0.04	-10000	0	-10000	0	0
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	0.03	0.067	0.25	20	-10000	0	20
mol:ACh	0.01	0.04	0.09	17	-0.11	10	27
RAB3GAP2	0.019	0.004	-10000	0	-10000	0	0
STX1A/SNAP25/VAMP2	0.034	0.057	0.25	1	-10000	0	1
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	0.075	0.091	0.2	82	-10000	0	82
UNC13B	0.018	0.005	-10000	0	-10000	0	0
CHRNA1	0.091	0.11	0.25	82	-10000	0	82
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	0.014	0.074	0.2	9	-0.36	6	15
SNAP25	0.016	0.062	0.1	53	-0.28	6	59
VAMP2	0.002	0.001	-10000	0	-10000	0	0
SYT1	0.011	0.098	0.25	9	-0.55	6	15
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.018	0.017	-10000	0	-10000	0	0
STX1A/SNAP25 fragment 1/VAMP2	0.034	0.057	0.25	1	-10000	0	1

×

BARD1 signaling events

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
BARD1/CSTF1	0.097	0.083	-10000	0	-10000	0	0
ATM	0.018	0.005	-10000	0	-10000	0	0
UBE2D3	0.019	0.001	-10000	0	-10000	0	0
PRKDC	0.019	0.004	-10000	0	-10000	0	0
ATR	0.019	0.002	-10000	0	-10000	0	0
UBE2L3	0.018	0.005	-10000	0	-10000	0	0
FANCD2	0.014	0.022	-10000	0	-10000	0	0
protein ubiquitination	0.09	0.08	0.3	10	-10000	0	10
XRCC5	0.019	0.004	-10000	0	-10000	0	0
XRCC6	0.019	0.004	-10000	0	-10000	0	0
M/R/N Complex	0.035	0.013	-10000	0	-10000	0	0
MRE11A	0.018	0.004	-10000	0	-10000	0	0
DNA-PK	0.035	0.013	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.003	0.085	-10000	0	-0.58	2	2
FANCF	0.019	0.004	-10000	0	-10000	0	0
BRCA1	0.021	0.021	0.25	2	-10000	0	2
CCNE1	0.037	0.066	0.25	21	-10000	0	21
CDK2/Cyclin E1	0.036	0.044	-10000	0	-10000	0	0
FANCG	0.018	0.005	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.1	0.085	0.19	119	-10000	0	119
FANCE	0.025	0.039	0.25	7	-10000	0	7
FANCC	0.019	0.003	-10000	0	-10000	0	0
NBN	0.018	0.005	-10000	0	-10000	0	0
FANCA	0.031	0.054	0.25	14	-10000	0	14
DNA repair	0.031	0.089	0.3	5	-0.54	1	6
BRCA1/BARD1/ubiquitin	0.1	0.085	0.19	119	-10000	0	119
BARD1/DNA-PK	0.1	0.075	-10000	0	-10000	0	0
FANCL	0.019	0.004	-10000	0	-10000	0	0
mRNA polyadenylation	-0.097	0.083	-10000	0	-10000	0	0
BRCA1/BARD1/CTIP/M/R/N Complex	0.038	0.062	0.21	2	-0.22	2	4
BRCA1/BACH1/BARD1/TopBP1	0.1	0.077	0.33	2	-10000	0	2
BRCA1/BARD1/P53	0.086	0.076	-10000	0	-10000	0	0
BARD1/CSTF1/BRCA1	0.1	0.079	0.33	2	-10000	0	2
BRCA1/BACH1	0.021	0.021	0.25	2	-10000	0	2
BARD1	0.13	0.12	0.25	120	-10000	0	120
PCNA	0.018	0.005	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	0.11	0.077	0.33	2	-10000	0	2
BRCA1/BARD1/UbcH7	0.096	0.079	0.33	2	-10000	0	2
BRCA1/BARD1/RAD51/PCNA	0.11	0.086	0.33	10	-10000	0	10
BARD1/DNA-PK/P53	0.083	0.075	-10000	0	-10000	0	0
BRCA1/BARD1/Ubiquitin	0.1	0.085	0.19	119	-10000	0	119
BRCA1/BARD1/CTIP	0.09	0.079	0.3	5	-10000	0	5
FA complex	0.015	0.04	-10000	0	-0.29	1	1
BARD1/EWS	0.097	0.083	-10000	0	-10000	0	0
RBBP8	-0.014	0.004	-10000	0	-10000	0	0
TP53	0.016	0.007	-10000	0	-10000	0	0
TOPBP1	0.019	0.002	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.083	0.074	-10000	0	-10000	0	0
BRCA1/BARD1	0.1	0.088	0.3	15	-10000	0	15
CSTF1	0.018	0.004	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.089	0.081	0.18	120	-10000	0	120
CDK2	0.018	0.004	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.037	0.063	0.25	20	-10000	0	20
RAD50	0.019	0.003	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.1	0.085	0.19	119	-10000	0	119
EWSR1	0.019	0.004	-10000	0	-10000	0	0

×

Arf6 signaling 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
CENTA1/KIF3B	0.014	0.057	-10000	0	-0.35	6	6
ARNO/beta Arrestin1-2	0.003	0.15	-10000	0	-0.78	9	9
EGFR	0.016	0.039	0.25	1	-0.55	1	2
EPHA2	0.018	0.005	-10000	0	-10000	0	0
USP6	0.02	0.022	0.25	2	-10000	0	2
IQSEC1	0.018	0.004	-10000	0	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.14	0.21	-10000	0	-0.38	102	102
ARRB2	0.009	0.021	-10000	0	-10000	0	0
mol:GTP	-0.002	0.052	0.15	3	-0.18	10	13
ARRB1	0.019	0.004	-10000	0	-10000	0	0
FBXO8	0.019	0.004	-10000	0	-10000	0	0
TSHR	0.038	0.072	0.25	25	-10000	0	25
EGF	-0.21	0.28	-10000	0	-0.55	101	101
somatostatin receptor activity	0	0	0.001	8	-0.001	27	35
ARAP2	0.016	0.036	-10000	0	-0.55	1	1
mol:GDP	-0.027	0.099	0.2	6	-0.25	24	30
mol:PI-3-4-5-P3	0	0	0.001	9	-0.001	8	17
ITGA2B	0.024	0.036	0.25	6	-10000	0	6
ARF6	0.018	0.004	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.044	0.016	-10000	0	-10000	0	0
ADAP1	0.005	0.086	-10000	0	-0.55	6	6
KIF13B	0.018	0.004	-10000	0	-10000	0	0
HGF/MET	0.004	0.096	-10000	0	-0.41	13	13
PXN	0.019	0.004	-10000	0	-10000	0	0
ARF6/GTP	-0.043	0.11	0.24	8	-0.25	28	36
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.11	0.18	-10000	0	-0.35	90	90
ADRB2	0.029	0.048	0.25	11	-10000	0	11
receptor agonist activity	0	0	0	6	0	23	29
actin filament binding	0	0	0.001	8	0	27	35
SRC	0.019	0.004	-10000	0	-10000	0	0
ITGB3	0.008	0.079	-10000	0	-0.55	5	5
GNAQ	0.019	0.003	-10000	0	-10000	0	0
EFA6/PI-4-5-P2	0	0.001	0.002	10	-0.001	11	21
ARF6/GDP	-0.023	0.15	0.25	4	-0.55	14	18
ARF6/GDP/GULP/ACAP1	-0.016	0.13	0.23	3	-0.38	12	15
alphaIIb/beta3 Integrin/paxillin/GIT1	0.043	0.055	-10000	0	-0.31	5	5
ACAP1	0.034	0.061	0.25	18	-10000	0	18
ACAP2	0.019	0.004	-10000	0	-10000	0	0
LHCGR/beta Arrestin2	0.019	0.038	0.21	8	-10000	0	8
EFNA1	0.018	0.004	-10000	0	-10000	0	0
HGF	-0.004	0.11	-10000	0	-0.55	10	10
CYTH3	-0.007	0.002	-10000	0	-10000	0	0
CYTH2	-0.022	0.19	-10000	0	-1	9	9
NCK1	0.019	0.002	-10000	0	-10000	0	0
fibronectin binding	0	0	0.001	11	0	15	26
endosomal lumen acidification	0	0	0	7	0	31	38
microtubule-based process	0	0	-10000	0	-10000	0	0
GULP1	-0.001	0.1	-10000	0	-0.55	9	9
GNAQ/ARNO	-0.01	0.18	-10000	0	-0.93	9	9
mol:Phosphatidic acid	0	0	-10000	0	-10000	0	0
PIP3-E	0	0	0	2	0	1	3
MET	0.012	0.061	-10000	0	-0.55	3	3
GNA14	-0.017	0.14	-10000	0	-0.55	16	16
GNA15	0.024	0.033	0.25	5	-10000	0	5
GIT1	0.019	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	0.001	9	-0.001	14	23
GNA11	0.017	0.036	-10000	0	-0.55	1	1
LHCGR	0.014	0.051	0.25	10	-10000	0	10
AGTR1	-0.073	0.21	-10000	0	-0.55	41	41
desensitization of G-protein coupled receptor protein signaling pathway	0.019	0.038	0.21	8	-10000	0	8
IPCEF1/ARNO	-0.11	0.2	-10000	0	-0.87	9	9
alphaIIb/beta3 Integrin	0.023	0.063	-10000	0	-0.39	5	5

×

Aurora C signaling

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
INCENP	0.021	0.021	0.25	2	-10000	0	2
Aurora C/Aurora B/INCENP	0.084	0.074	0.31	3	-10000	0	3
metaphase	0	0	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
H3F3B	0.013	0.024	-10000	0	-0.31	1	1
AURKB	0.1	0.12	0.25	94	-10000	0	94
AURKC	0.022	0.026	0.25	3	-10000	0	3

×

S1P1 pathway

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	0.016	0.024	-10000	0	-10000	0	0
PDGFRB	0.009	0.023	0.25	1	-10000	0	1
SPHK1	0.023	0.093	-10000	0	-0.64	2	2
mol:S1P	0.012	0.09	0.31	2	-0.55	2	4
S1P1/S1P/Gi	-0.11	0.21	0.24	1	-0.45	55	56
GNAO1	-0.058	0.19	0.25	1	-0.55	31	32
PDGFB-D/PDGFRB/PLCgamma1	-0.091	0.2	0.24	2	-0.43	47	49
PLCG1	-0.11	0.19	0.22	1	-0.43	53	54
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.009	0.023	0.25	1	-10000	0	1
GNAI2	0.01	0.02	-10000	0	-10000	0	0
GNAI3	0.01	0.019	-10000	0	-10000	0	0
GNAI1	0.001	0.072	-10000	0	-0.55	4	4
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	-0.014	0.013	-10000	0	-10000	0	0
S1P1/S1P	-0.008	0.081	0.22	3	-0.36	2	5
negative regulation of cAMP metabolic process	-0.11	0.2	0.24	1	-0.43	55	56
MAPK3	-0.15	0.26	0.28	1	-0.6	55	56
calcium-dependent phospholipase C activity	-0.003	0.004	-10000	0	-10000	0	0
Rac1/GDP	0.013	0.004	-10000	0	-10000	0	0
RhoA/GDP	0.014	0.003	-10000	0	-10000	0	0
KDR	0.011	0.017	-10000	0	-10000	0	0
PLCB2	0.004	0.091	0.23	6	-0.33	2	8
RAC1	0.018	0.006	-10000	0	-10000	0	0
RhoA/GTP	-0.017	0.059	-10000	0	-0.32	2	2
receptor internalization	-0.008	0.077	0.2	3	-0.34	2	5
PTGS2	-0.22	0.42	-10000	0	-1	51	51
Rac1/GTP	-0.018	0.058	-10000	0	-0.32	2	2
RHOA	0.019	0.004	-10000	0	-10000	0	0
VEGFA	0.011	0.017	-10000	0	-10000	0	0
negative regulation of T cell proliferation	-0.11	0.2	0.24	1	-0.43	55	56
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	-0.025	0.14	-10000	0	-0.56	16	16
MAPK1	-0.14	0.26	0.28	1	-0.61	53	54
S1P1/S1P/PDGFB-D/PDGFRB	-0.007	0.091	0.24	3	-0.3	2	5
ABCC1	0.009	0.018	-10000	0	-10000	0	0

×

S1P4 pathway

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
mol:S1P	0	0	-10000	0	-10000	0	0
GNAO1	-0.05	0.19	0.25	1	-0.55	31	32
CDC42/GTP	-0.037	0.12	-10000	0	-0.27	42	42
PLCG1	-0.045	0.12	-10000	0	-0.28	42	42
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.019	0.003	-10000	0	-10000	0	0
GNAI3	0.019	0.003	-10000	0	-10000	0	0
G12/G13	0.026	0.009	-10000	0	-10000	0	0
cell migration	-0.036	0.12	-10000	0	-0.26	42	42
S1PR5	0.029	0.05	0.25	12	-10000	0	12
S1PR4	0.024	0.033	0.25	5	-10000	0	5
MAPK3	-0.044	0.12	-10000	0	-0.28	41	41
MAPK1	-0.044	0.12	-10000	0	-0.3	32	32
S1P/S1P5/Gi	-0.037	0.12	-10000	0	-0.29	41	41
GNAI1	0.009	0.071	-10000	0	-0.55	4	4
CDC42/GDP	0.014	0.003	-10000	0	-10000	0	0
S1P/S1P5/G12	0.029	0.03	-10000	0	-10000	0	0
RHOA	0.003	0.063	0.36	2	-10000	0	2
S1P/S1P4/Gi	-0.041	0.13	-10000	0	-0.29	43	43
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	-0.017	0.14	-10000	0	-0.55	16	16
S1P/S1P4/G12/G13	0.036	0.023	-10000	0	-10000	0	0
GNA12	0.018	0.005	-10000	0	-10000	0	0
GNA13	0.019	0.004	-10000	0	-10000	0	0
CDC42	0.019	0.004	-10000	0	-10000	0	0

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.011	0.003	-10000	0	-10000	0	0
ADCY5	-0.13	0.16	0.23	1	-0.35	93	94
ADCY6	-0.011	0.007	-10000	0	-10000	0	0
ADCY7	-0.011	0.003	-10000	0	-10000	0	0
ADCY1	0.005	0.042	0.23	3	-10000	0	3
ADCY2	-0.024	0.1	0.23	4	-0.35	20	24
ADCY3	-0.01	0.01	-10000	0	-10000	0	0
ADCY8	-0.038	0.1	0.23	1	-0.35	25	26
PRKCE	-0.007	0.001	-10000	0	-10000	0	0
ADCY9	-0.011	0.003	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	-0.033	0.097	0.22	5	-0.24	15	20

×

Ephrin A reverse signaling

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
MAPKKK cascade	0.049	0.088	0.32	1	-0.35	6	7
EFNA5	0.009	0.092	0.25	4	-0.55	6	10
FYN	0.002	0.067	0.21	2	-0.32	6	8
neuron projection morphogenesis	0.049	0.088	0.32	1	-0.35	6	7
cell-cell signaling	0	0	-10000	0	-10000	0	0
Ephrin A5/EPHA5	0.05	0.089	0.32	1	-0.35	6	7
EPHA5	0.062	0.1	0.25	57	-10000	0	57

×

IL2 signaling events mediated by STAT5

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
GAB2	0.019	0.005	-10000	0	-10000	0	0
ELF1	0.036	0.077	-10000	0	-0.35	5	5
CCNA2	0.087	0.11	0.25	74	-10000	0	74
PIK3CA	0.019	0.004	-10000	0	-10000	0	0
JAK3	0.037	0.062	0.26	19	-10000	0	19
PIK3R1	0.021	0.015	0.25	1	-10000	0	1
JAK1	0.019	0.005	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.042	0.13	0.31	20	-0.61	2	22
SHC1	0.019	0.005	-10000	0	-10000	0	0
SP1	0.014	0.055	-10000	0	-0.36	5	5
IL2RA	0.031	0.16	0.28	48	-0.76	5	53
IL2RB	0.048	0.077	0.26	31	-10000	0	31
SOS1	0.019	0.005	-10000	0	-10000	0	0
IL2RG	0.039	0.089	0.26	26	-0.55	2	28
G1/S transition of mitotic cell cycle	0.037	0.14	0.39	4	-0.72	5	9
PTPN11	0.019	0.005	-10000	0	-10000	0	0
CCND2	-0.025	0.11	0.43	1	-0.81	5	6
LCK	0.043	0.083	0.26	28	-0.55	1	29
GRB2	0.019	0.004	-10000	0	-10000	0	0
IL2	-0.015	0.008	-10000	0	-10000	0	0
CDK6	0.016	0.036	-10000	0	-0.55	1	1
CCND3	0.055	0.14	0.53	5	-0.67	1	6

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.023	0.099	-10000	0	-0.35	1	1
Syndecan-4/Syndesmos	0.001	0.18	0.34	1	-0.54	9	10
positive regulation of JNK cascade	0.004	0.18	0.32	3	-0.48	10	13
Syndecan-4/ADAM12	0.063	0.21	0.36	24	-0.56	7	31
CCL5	0.056	0.086	0.25	40	-10000	0	40
Rac1/GDP	0.013	0.004	-10000	0	-10000	0	0
DNM2	0.018	0.005	-10000	0	-10000	0	0
ITGA5	0.018	0.004	-10000	0	-10000	0	0
SDCBP	0.018	0.005	-10000	0	-10000	0	0
PLG	-0.11	0.21	-10000	0	-0.53	50	50
ADAM12	0.13	0.12	0.25	126	-10000	0	126
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0.019	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.03	0.024	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	0	0.19	0.34	2	-0.53	13	15
Syndecan-4/CXCL12/CXCR4	0.005	0.19	0.34	3	-0.51	10	13
Syndecan-4/Laminin alpha3	0.008	0.19	0.34	2	-0.57	9	11
MDK	0.049	0.079	0.25	33	-10000	0	33
Syndecan-4/FZD7	0.002	0.18	0.34	1	-0.49	12	13
Syndecan-4/Midkine	0.017	0.19	0.36	3	-0.5	12	15
FZD7	0.017	0.036	-10000	0	-0.55	1	1
Syndecan-4/FGFR1/FGF	-0.002	0.17	0.32	1	-0.51	9	10
THBS1	0.014	0.05	-10000	0	-0.55	2	2
integrin-mediated signaling pathway	0.03	0.2	0.34	13	-0.5	12	25
positive regulation of MAPKKK cascade	0.004	0.18	0.32	3	-0.48	10	13
Syndecan-4/TACI	-0.001	0.17	0.34	1	-0.5	11	12
CXCR4	0.032	0.054	0.25	14	-10000	0	14
cell adhesion	0.03	0.05	0.19	8	-10000	0	8
Syndecan-4/Dynamin	-0.004	0.17	-10000	0	-0.52	9	9
Syndecan-4/TSP1	0	0.19	0.34	1	-0.52	12	13
Syndecan-4/GIPC	-0.002	0.17	-10000	0	-0.52	9	9
Syndecan-4/RANTES	0.022	0.2	0.36	7	-0.5	12	19
ITGB1	0.019	0.004	-10000	0	-10000	0	0
LAMA1	0.016	0.1	0.25	12	-0.55	6	18
LAMA3	0.031	0.089	0.25	20	-0.55	3	23
RAC1	0.018	0.006	-10000	0	-10000	0	0
PRKCA	0.013	0.14	0.82	7	-10000	0	7
Syndecan-4/alpha-Actinin	0.001	0.18	0.34	1	-0.53	10	11
TFPI	-0.008	0.12	-10000	0	-0.55	12	12
F2	0.023	0.028	0.26	2	-10000	0	2
alpha5/beta1 Integrin	0.026	0.009	-10000	0	-10000	0	0
positive regulation of cell adhesion	-0.006	0.18	0.33	1	-0.57	11	12
ACTN1	0.018	0.004	-10000	0	-10000	0	0
TNC	0.069	0.12	0.25	62	-0.55	3	65
Syndecan-4/CXCL12	-0.005	0.18	0.34	1	-0.51	11	12
FGF6	-0.015	0.004	-10000	0	-10000	0	0
RHOA	0.019	0.004	-10000	0	-10000	0	0
CXCL12	0.007	0.079	-10000	0	-0.55	5	5
TNFRSF13B	-0.014	0.006	-10000	0	-10000	0	0
FGF2	0.008	0.079	-10000	0	-0.55	5	5
FGFR1	0.018	0.005	-10000	0	-10000	0	0
Syndecan-4/PI-4-5-P2	-0.014	0.17	-10000	0	-0.5	12	12
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.06	0.096	0.26	48	-10000	0	48
cell migration	-0.017	0.01	-10000	0	-10000	0	0
PRKCD	0.009	0.023	-10000	0	-10000	0	0
vasculogenesis	0.001	0.18	0.33	1	-0.49	12	13
SDC4	-0.01	0.18	-10000	0	-0.53	12	12
Syndecan-4/Tenascin C	0.029	0.2	0.34	12	-0.53	11	23
Syndecan-4/PI-4-5-P2/PKC alpha	-0.026	0.015	-10000	0	-10000	0	0
Syndecan-4/Syntenin	0.003	0.18	0.34	1	-0.51	10	11
MMP9	0.11	0.12	0.26	100	-0.55	1	101
Rac1/GTP	0.03	0.05	0.19	8	-10000	0	8
cytoskeleton organization	0.002	0.17	0.33	1	-0.5	10	11
GIPC1	0.018	0.004	-10000	0	-10000	0	0
Syndecan-4/TFPI	-0.011	0.2	0.34	1	-0.5	17	18

×

Angiopoietin receptor Tie2-mediated signaling

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
AKT1	-0.045	0.25	0.45	1	-0.91	17	18
NCK1/PAK1/Dok-R	-0.043	0.11	-10000	0	-0.42	17	17
NCK1/Dok-R	-0.05	0.3	-10000	0	-1.1	17	17
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
mol:beta2-estradiol	0.012	0.058	0.24	16	-10000	0	16
RELA	0.019	0.003	-10000	0	-10000	0	0
SHC1	0.018	0.006	-10000	0	-10000	0	0
Rac/GDP	0.013	0.004	-10000	0	-10000	0	0
F2	0.012	0.072	0.26	18	-10000	0	18
TNIP2	0.019	0.004	-10000	0	-10000	0	0
NF kappa B/RelA	-0.046	0.28	-10000	0	-1	17	17
FN1	0.063	0.092	0.25	48	-10000	0	48
PLD2	-0.071	0.3	-10000	0	-1.2	17	17
PTPN11	0.018	0.004	-10000	0	-10000	0	0
GRB14	-0.15	0.26	-10000	0	-0.55	75	75
ELK1	-0.06	0.27	-10000	0	-1	17	17
GRB7	-0.077	0.21	0.25	1	-0.55	42	43
PAK1	0.018	0.004	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.029	0.3	-10000	0	-1.1	17	17
CDKN1A	-0.035	0.18	-10000	0	-0.61	16	16
ITGA5	0.018	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.051	0.3	-10000	0	-1.1	17	17
CRK	0.018	0.005	-10000	0	-10000	0	0
mol:NO	-0.027	0.19	0.48	2	-0.65	17	19
PLG	-0.13	0.32	-10000	0	-1.2	17	17
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.051	0.23	-10000	0	-0.87	17	17
GRB2	0.019	0.003	-10000	0	-10000	0	0
PIK3R1	0.02	0.016	0.25	1	-10000	0	1
ANGPT2	-0.052	0.19	-10000	0	-0.68	11	11
BMX	-0.076	0.3	-10000	0	-1.2	17	17
ANGPT1	-0.071	0.32	-10000	0	-1.3	16	16
tube development	-0.039	0.2	0.39	2	-0.68	17	19
ANGPT4	0.023	0.054	0.25	12	-10000	0	12
response to hypoxia	-0.004	0.018	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.16	0.34	-10000	0	-1.3	17	17
alpha5/beta1 Integrin	0.026	0.009	-10000	0	-10000	0	0
FGF2	0.006	0.079	-10000	0	-0.55	5	5
STAT5A (dimer)	-0.043	0.23	-10000	0	-0.78	17	17
mol:L-citrulline	-0.027	0.19	0.48	2	-0.65	17	19
AGTR1	-0.071	0.21	-10000	0	-0.55	41	41
MAPK14	-0.075	0.32	-10000	0	-1.1	19	19
Tie2/SHP2	-0.05	0.21	-10000	0	-1.2	6	6
TEK	-0.056	0.23	-10000	0	-1.2	7	7
RPS6KB1	-0.047	0.24	-10000	0	-0.87	17	17
Angiotensin II/AT1	-0.049	0.15	-10000	0	-0.39	42	42
Tie2/Ang1/GRB2	-0.069	0.32	-10000	0	-1.2	17	17
MAPK3	-0.066	0.27	-10000	0	-1.1	17	17
MAPK1	-0.067	0.27	-10000	0	-1.1	17	17
Tie2/Ang1/GRB7	-0.12	0.33	-10000	0	-1.2	17	17
NFKB1	0.019	0.001	-10000	0	-10000	0	0
MAPK8	-0.074	0.3	-10000	0	-1.2	17	17
PI3K	-0.057	0.28	-10000	0	-1.1	17	17
FES	-0.067	0.3	-10000	0	-1.1	17	17
Crk/Dok-R	-0.052	0.3	-10000	0	-1.1	17	17
Tie2/Ang1/ABIN2	-0.07	0.32	-10000	0	-1.2	17	17
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.037	0.22	0.45	1	-0.8	17	18
STAT5A	0.019	0.001	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.039	0.24	-10000	0	-0.86	17	17
Tie2/Ang2	-0.059	0.26	-10000	0	-0.94	17	17
Tie2/Ang1	-0.073	0.34	-10000	0	-1.3	17	17
FOXO1	-0.03	0.22	0.46	2	-0.81	17	19
ELF1	0.015	0.024	-10000	0	-10000	0	0
ELF2	-0.066	0.3	-10000	0	-1.1	17	17
mol:Choline	-0.066	0.28	-10000	0	-1.1	17	17
cell migration	-0.019	0.064	-10000	0	-0.24	17	17
FYN	-0.047	0.22	-10000	0	-0.78	17	17
DOK2	0.028	0.046	0.25	10	-10000	0	10
negative regulation of cell cycle	-0.03	0.17	0.38	2	-0.55	16	18
ETS1	0.004	0.062	-10000	0	-0.25	14	14
PXN	-0.03	0.2	-10000	0	-0.71	17	17
ITGB1	0.019	0.004	-10000	0	-10000	0	0
NOS3	-0.034	0.21	0.6	1	-0.75	17	18
RAC1	0.018	0.006	-10000	0	-10000	0	0
TNF	0.014	0.074	0.26	8	-0.25	13	21
MAPKKK cascade	-0.066	0.28	-10000	0	-1.1	17	17
RASA1	0.019	0.002	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.07	0.32	-10000	0	-1.2	17	17
NCK1	0.019	0.002	-10000	0	-10000	0	0
vasculogenesis	-0.022	0.17	0.47	2	-0.58	17	19
mol:Phosphatidic acid	-0.066	0.28	-10000	0	-1.1	17	17
mol:Angiotensin II	0.002	0.005	-10000	0	-10000	0	0
mol:NADP	-0.027	0.19	0.48	2	-0.65	17	19
Rac1/GTP	-0.042	0.22	-10000	0	-0.81	17	17
MMP2	-0.067	0.31	-10000	0	-1.2	17	17

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	-0.082	0.22	0.25	2	-0.55	46	48
oxygen homeostasis	0	0	-10000	0	-10000	0	0
TCEB2	0.019	0.003	-10000	0	-10000	0	0
TCEB1	0.018	0.005	-10000	0	-10000	0	0
HIF1A/p53	-0.002	0.087	-10000	0	-0.29	15	15
HIF1A	-0.018	0.07	-10000	0	-0.3	12	12
COPS5	0.018	0.005	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.045	0.026	-10000	0	-10000	0	0
FIH (dimer)	0.018	0.005	-10000	0	-10000	0	0
CDKN2A	0.18	0.11	0.25	182	-10000	0	182
ARNT/IPAS	-0.047	0.16	-10000	0	-0.41	41	41
HIF1AN	0.018	0.005	-10000	0	-10000	0	0
GNB2L1	0.018	0.004	-10000	0	-10000	0	0
HIF1A/ARNT	-0.001	0.087	-10000	0	-0.3	14	14
CUL2	0.019	0.004	-10000	0	-10000	0	0
OS9	0.016	0.008	-10000	0	-10000	0	0
RACK1/Elongin B/Elongin C	0.035	0.013	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF1A/Hsp90	0.001	0.089	-10000	0	-0.3	15	15
PHD1-3/OS9	-0.002	0.1	-10000	0	-0.32	22	22
HIF1A/RACK1/Elongin B/Elongin C	0.011	0.09	-10000	0	-0.36	4	4
VHL	0.018	0.004	-10000	0	-10000	0	0
HSP90AA1	0.019	0.004	-10000	0	-10000	0	0
HIF1A/JAB1	-0.001	0.088	-10000	0	-0.3	15	15
EGLN3	-0.044	0.18	-10000	0	-0.55	28	28
EGLN2	0.018	0.005	-10000	0	-10000	0	0
EGLN1	0.019	0.004	-10000	0	-10000	0	0
TP53	0.016	0.007	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.004	0.1	-10000	0	-0.5	9	9
ARNT	0.018	0.005	-10000	0	-10000	0	0
ARD1A	0	0	-10000	0	-10000	0	0
RBX1	0.019	0.004	-10000	0	-10000	0	0
HIF1A/p19ARF	0.097	0.12	0.24	20	-0.31	4	24

×

p75(NTR)-mediated 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
Sortilin/TRAF6	0.027	0.007	-10000	0	-10000	0	0
Necdin/E2F1	0.029	0.14	-10000	0	-0.36	22	22
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.042	0.079	-10000	0	-0.31	9	9
NGF (dimer)/p75(NTR)/BEX1	-0.012	0.16	0.33	2	-0.36	40	42
NT-4/5 (dimer)/p75(NTR)	0.018	0.089	-10000	0	-0.41	9	9
IKBKB	0.019	0.004	-10000	0	-10000	0	0
AKT1	-0.025	0.07	0.24	1	-0.31	11	12
IKBKG	0.019	0.004	-10000	0	-10000	0	0
BDNF	0.011	0.072	0.25	1	-0.55	4	5
MGDIs/NGR/p75(NTR)/LINGO1	0.047	0.099	0.33	9	-0.33	8	17
FURIN	0.019	0.004	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	0.025	0.092	-10000	0	-0.35	13	13
LINGO1	0.023	0.033	0.25	5	-10000	0	5
Sortilin/TRAF6/NRIF	-0.026	0.013	-10000	0	-10000	0	0
proBDNF (dimer)	0.011	0.072	0.25	1	-0.55	4	5
NTRK1	0.015	0.091	0.25	9	-0.55	5	14
RTN4R	0.047	0.077	0.25	31	-10000	0	31
neuron apoptosis	-0.01	0.11	-10000	0	-0.45	3	3
IRAK1	0.019	0.003	-10000	0	-10000	0	0
SHC1	-0.022	0.073	0.2	1	-0.35	10	11
ARHGDIA	0.019	0.004	-10000	0	-10000	0	0
RhoA/GTP	0.014	0.003	-10000	0	-10000	0	0
Gamma Secretase	0.044	0.026	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.037	0.082	-10000	0	-0.32	10	10
MAGEH1	0.018	0.005	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	0.004	0.14	-10000	0	-0.34	30	30
Mammalian IAPs/DIABLO	0.039	0.043	-10000	0	-0.32	3	3
proNGF (dimer)	0.015	0.052	0.25	1	-0.55	2	3
MAGED1	0.018	0.004	-10000	0	-10000	0	0
APP	0.016	0.036	-10000	0	-0.55	1	1
NT-4/5 (dimer)	-0.016	0.004	-10000	0	-10000	0	0
ZNF274	0.019	0.004	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	0.012	0.07	-10000	0	-0.3	11	11
NGF	0.015	0.052	0.25	1	-0.55	2	3
cell cycle arrest	-0.011	0.082	0.22	8	-0.28	11	19
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.001	0.064	-10000	0	-0.26	9	9
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.027	0.081	-10000	0	-0.35	9	9
NCSTN	0.018	0.005	-10000	0	-10000	0	0
mol:GTP	0.028	0.084	-10000	0	-0.35	10	10
PSENEN	0.018	0.005	-10000	0	-10000	0	0
mol:ceramide	-0.024	0.071	-10000	0	-0.32	11	11
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.027	0.096	-10000	0	-0.35	7	7
p75(NTR)/beta APP	0.018	0.096	-10000	0	-0.44	9	9
BEX1	-0.038	0.2	0.25	16	-0.55	32	48
mol:GDP	-0.02	0.073	-10000	0	-0.35	11	11
NGF (dimer)	-0.15	0.2	-10000	0	-0.36	112	112
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.054	0.095	0.33	9	-0.31	8	17
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
RAC1/GTP	0.021	0.074	-10000	0	-0.3	11	11
MYD88	0.019	0.003	-10000	0	-10000	0	0
CHUK	0.018	0.005	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	0.028	0.085	-10000	0	-0.35	10	10
RHOB	0.016	0.036	-10000	0	-0.55	1	1
RHOA	0.019	0.004	-10000	0	-10000	0	0
MAGE-G1/E2F1	0.072	0.074	-10000	0	-10000	0	0
NT3 (dimer)	-0.042	0.19	0.25	8	-0.55	29	37
TP53	-0.025	0.075	0.34	1	-0.3	12	13
PRDM4	-0.023	0.073	0.19	1	-0.32	11	12
BDNF (dimer)	-0.27	0.25	-10000	0	-0.43	166	166
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
SORT1	0.019	0.003	-10000	0	-10000	0	0
activation of caspase activity	0.037	0.076	-10000	0	-0.31	9	9
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.038	0.085	-10000	0	-0.32	11	11
RHOC	0.019	0.003	-10000	0	-10000	0	0
XIAP	0.019	0.002	-10000	0	-10000	0	0
MAPK10	-0.076	0.14	-10000	0	-0.47	11	11
DIABLO	0.019	0.004	-10000	0	-10000	0	0
SMPD2	-0.024	0.071	0.19	1	-0.32	11	12
APH1B	0.019	0.004	-10000	0	-10000	0	0
APH1A	0.018	0.005	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	0.029	0.088	-10000	0	-0.35	11	11
PSEN1	0.018	0.005	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.026	0.009	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.026	0.17	-10000	0	-0.42	36	36
MAPK8	-0.011	0.097	0.26	7	-0.35	9	16
MAPK9	-0.012	0.094	0.26	3	-0.35	9	12
APAF1	0.019	0.004	-10000	0	-10000	0	0
NTF3	-0.042	0.19	0.25	8	-0.55	29	37
NTF4	-0.016	0.004	-10000	0	-10000	0	0
NDN	-0.031	0.16	-10000	0	-0.55	22	22
RAC1/GDP	0.013	0.004	-10000	0	-10000	0	0
RhoA-B-C/GDP	0.032	0.08	-10000	0	-0.32	10	10
p75 CTF/Sortilin/TRAF6/NRIF	0.045	0.016	-10000	0	-10000	0	0
RhoA-B-C/GTP	0.027	0.084	-10000	0	-0.35	10	10
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.039	0.088	-10000	0	-0.31	13	13
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.035	0.089	-10000	0	-0.32	13	13
PRKACB	0.018	0.004	-10000	0	-10000	0	0
proBDNF (dimer)/p75 ECD	0.021	0.055	-10000	0	-0.41	4	4
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.011	0.061	-10000	0	-0.55	3	3
BIRC2	0.018	0.005	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.016	0.11	0.28	7	-0.33	11	18
BAD	-0.031	0.12	0.42	4	-0.41	10	14
RIPK2	0.018	0.005	-10000	0	-10000	0	0
NGFR	0.011	0.12	0.25	13	-0.55	9	22
CYCS	-0.018	0.077	0.35	1	-0.31	10	11
ADAM17	0.019	0.004	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.037	0.08	-10000	0	-0.32	9	9
BCL2L11	-0.032	0.12	0.4	4	-0.41	10	14
BDNF (dimer)/p75(NTR)	0.014	0.1	-10000	0	-0.4	13	13
PI3K	0.037	0.084	-10000	0	-0.32	11	11
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.038	0.082	-10000	0	-0.32	10	10
NDNL2	0.019	0.004	-10000	0	-10000	0	0
YWHAE	0.018	0.005	-10000	0	-10000	0	0
PRKCI	0.019	0.003	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	0.018	0.098	-10000	0	-0.41	11	11
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.037	0.085	-10000	0	-0.32	11	11
TRAF6	0.019	0.004	-10000	0	-10000	0	0
RAC1	0.018	0.006	-10000	0	-10000	0	0
PRKCZ	-0.022	0.15	0.25	1	-0.55	18	19
PLG	-0.12	0.21	-10000	0	-0.55	50	50
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.026	0.08	-10000	0	-0.33	14	14
SQSTM1	0.018	0.005	-10000	0	-10000	0	0
NGFRAP1	0.019	0.003	-10000	0	-10000	0	0
CASP3	-0.031	0.12	0.33	6	-0.38	11	17
E2F1	0.091	0.11	0.25	78	-10000	0	78
CASP9	0.018	0.005	-10000	0	-10000	0	0
IKK complex	-0.001	0.11	-10000	0	-0.34	4	4
NGF (dimer)/TRKA	0.021	0.079	-10000	0	-0.41	7	7
MMP7	-0.17	0.26	-10000	0	-0.55	84	84
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.042	0.084	-10000	0	-0.31	11	11
MMP3	-0.2	0.27	0.25	4	-0.55	98	102
APAF-1/Caspase 9	-0.043	0.055	-10000	0	-10000	0	0

×

S1P5 pathway

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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.034	0.12	0.28	31	-10000	0	31
GNAI2	0.019	0.003	-10000	0	-10000	0	0
S1P/S1P5/G12	0.029	0.03	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.05	0.19	0.25	1	-0.55	31	32
RhoA/GTP	-0.034	0.12	-10000	0	-0.28	31	31
negative regulation of cAMP metabolic process	-0.037	0.12	-10000	0	-0.28	41	41
GNAZ	-0.017	0.14	-10000	0	-0.55	16	16
GNAI3	0.019	0.003	-10000	0	-10000	0	0
GNA12	0.018	0.005	-10000	0	-10000	0	0
S1PR5	0.029	0.05	0.25	12	-10000	0	12
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.037	0.12	-10000	0	-0.29	41	41
RhoA/GDP	0.014	0.003	-10000	0	-10000	0	0
RHOA	0.019	0.004	-10000	0	-10000	0	0
GNAI1	0.009	0.071	-10000	0	-0.55	4	4

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.019	0.016	0.25	1	-10000	0	1
CD4-positive alpha-beta T cell lineage commitment	0	0.001	-10000	0	-10000	0	0
cytokine production during immune response	-0.085	0.12	0.41	1	-0.39	13	14
IL27/IL27R/JAK1	0.15	0.15	0.58	10	-10000	0	10
TBX21	0.13	0.17	0.43	44	-10000	0	44
IL12B	0.03	0.057	0.27	12	-10000	0	12
IL12A	-0.001	0.017	0.15	2	-10000	0	2
IL6ST	0.052	0.082	0.26	27	-0.56	1	28
IL27RA/JAK1	0.053	0.059	-10000	0	-10000	0	0
IL27	0.04	0.064	0.29	15	-10000	0	15
TYK2	0.03	0.021	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.018	0.11	-10000	0	-0.47	2	2
T-helper 2 cell differentiation	-0.085	0.12	0.41	1	-0.39	13	14
T cell proliferation during immune response	-0.085	0.12	0.41	1	-0.39	13	14
MAPKKK cascade	0.085	0.12	0.39	13	-0.41	1	14
STAT3	0.019	0.001	-10000	0	-10000	0	0
STAT2	0.019	0.004	-10000	0	-10000	0	0
STAT1	0.023	0.016	0.26	1	-10000	0	1
IL12RB1	0.04	0.066	0.26	20	-10000	0	20
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	0.11	0.15	0.43	26	-10000	0	26
IL27/IL27R/JAK2/TYK2	0.081	0.12	0.4	12	-0.41	1	13
positive regulation of T cell mediated cytotoxicity	0.085	0.12	0.39	13	-0.41	1	14
STAT1 (dimer)	0.17	0.2	0.54	40	-10000	0	40
JAK2	0.027	0.023	0.29	1	-10000	0	1
JAK1	0.021	0.007	-10000	0	-10000	0	0
STAT2 (dimer)	0.094	0.11	0.36	10	-0.4	1	11
T cell proliferation	0.047	0.15	0.35	15	-0.59	2	17
IL12/IL12R/TYK2/JAK2	0.081	0.13	0.44	6	-0.61	3	9
IL17A	-0.019	0.11	-10000	0	-0.47	2	2
mast cell activation	-0.085	0.12	0.41	1	-0.39	13	14
IFNG	0.044	0.062	0.14	64	-0.1	2	66
T cell differentiation	0.003	0.006	0.017	32	-10000	0	32
STAT3 (dimer)	0.094	0.11	0.36	10	-0.4	1	11
STAT5A (dimer)	0.094	0.11	0.36	10	-0.4	1	11
STAT4 (dimer)	0.097	0.12	0.38	16	-0.4	1	17
STAT4	0.026	0.041	0.25	8	-10000	0	8
T cell activation	-0.003	0.009	-10000	0	-0.11	2	2
IL27R/JAK2/TYK2	0.086	0.088	-10000	0	-10000	0	0
GATA3	-0.15	0.4	0.53	3	-1.4	25	28
IL18	-0.017	0.074	-10000	0	-0.4	9	9
positive regulation of mast cell cytokine production	0.091	0.11	0.35	12	-0.39	1	13
IL27/EBI3	0.069	0.087	0.3	25	-10000	0	25
IL27RA	0.04	0.067	-10000	0	-10000	0	0
IL6	-0.033	0.17	0.25	3	-0.55	24	27
STAT5A	0.019	0.001	-10000	0	-10000	0	0
monocyte differentiation	0.002	0.003	-10000	0	-10000	0	0
IL2	-0.029	0.034	-10000	0	-10000	0	0
IL1B	-0.014	0.078	0.15	7	-0.4	9	16
EBI3	0.05	0.074	0.28	23	-10000	0	23
TNF	0.002	0.029	0.15	9	-10000	0	9

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.02	0.015	0.25	1	-10000	0	1
Jak2/Leptin Receptor	-0.036	0.14	-10000	0	-0.43	16	16
PTP1B/AKT1	-0.04	0.098	-10000	0	-0.33	13	13
FYN	0.018	0.005	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.051	0.1	-10000	0	-0.33	16	16
EGFR	-0.003	0.045	0.24	1	-0.56	1	2
EGF/EGFR	-0.13	0.17	-10000	0	-0.34	95	95
CSF1	0.024	0.033	0.25	5	-10000	0	5
AKT1	0.017	0.008	-10000	0	-10000	0	0
INSR	0.016	0.01	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.097	0.15	-10000	0	-0.33	55	55
Insulin Receptor/Insulin	-0.026	0.089	-10000	0	-0.37	5	5
HCK	0.03	0.05	0.25	12	-10000	0	12
CRK	0.018	0.005	-10000	0	-10000	0	0
TYK2	-0.04	0.11	0.26	8	-0.33	14	22
EGF	-0.21	0.28	-10000	0	-0.55	101	101
YES1	0.018	0.005	-10000	0	-10000	0	0
CAV1	-0.076	0.12	0.21	3	-0.32	24	27
TXN	0.005	0.018	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.037	0.1	-10000	0	-0.34	13	13
cell migration	0.051	0.1	0.33	16	-10000	0	16
STAT3	0.019	0.002	-10000	0	-10000	0	0
PRLR	-0.012	0.15	0.25	10	-0.55	17	27
ITGA2B	0.024	0.036	0.25	6	-10000	0	6
CSF1R	0.012	0.061	-10000	0	-0.55	3	3
Prolactin Receptor/Prolactin	0.022	0.13	0.36	5	-0.4	17	22
FGR	0.019	0.004	-10000	0	-10000	0	0
PTP1B/p130 Cas	-0.041	0.1	-10000	0	-0.32	16	16
Crk/p130 Cas	-0.04	0.1	-10000	0	-0.33	13	13
DOK1	-0.041	0.1	0.27	1	-0.36	11	12
JAK2	-0.039	0.14	-10000	0	-0.43	19	19
Jak2/Leptin Receptor/Leptin	-0.028	0.11	-10000	0	-0.38	6	6
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
PTPN1	-0.051	0.1	-10000	0	-0.34	16	16
LYN	0.018	0.005	-10000	0	-10000	0	0
CDH2	-0.089	0.22	-10000	0	-0.55	48	48
SRC	-0.011	0.077	-10000	0	-0.46	5	5
ITGB3	0.008	0.079	-10000	0	-0.55	5	5
CAT1/PTP1B	-0.072	0.15	0.28	3	-0.41	18	21
CAPN1	0.017	0.008	-10000	0	-10000	0	0
CSK	0.019	0.004	-10000	0	-10000	0	0
PI3K	-0.025	0.09	-10000	0	-0.36	5	5
mol:H2O2	-0.001	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	-0.025	0.1	-10000	0	-0.34	6	6
negative regulation of transcription	-0.039	0.14	-10000	0	-0.42	19	19
FCGR2A	0.021	0.026	0.25	3	-10000	0	3
FER	0.004	0.019	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	0.022	0.063	-10000	0	-0.39	5	5
BLK	0.036	0.076	0.25	27	-10000	0	27
Insulin Receptor/Insulin/Shc	0.031	0.015	-10000	0	-10000	0	0
RHOA	0.017	0.008	-10000	0	-10000	0	0
LEPR	0.019	0.004	-10000	0	-10000	0	0
BCAR1	0.018	0.005	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.019	0.003	-10000	0	-10000	0	0
mol:NADPH	-0.002	0.004	-10000	0	-10000	0	0
TRPV6	-0.032	0.15	0.23	4	-0.42	12	16
PRL	0.048	0.095	0.25	44	-10000	0	44
SOCS3	0.011	0.098	-10000	0	-1.1	2	2
SPRY2	0.008	0.052	0.25	5	-0.55	1	6
Insulin Receptor/Insulin/IRS1	0.031	0.019	-10000	0	-10000	0	0
CSF1/CSF1R	-0.041	0.12	0.26	1	-0.4	12	13
Ras protein signal transduction	0.02	0.098	0.57	7	-10000	0	7
IRS1	0.019	0.016	0.25	1	-10000	0	1
INS	-0.007	0.016	-10000	0	-10000	0	0
LEP	0.022	0.064	0.25	17	-10000	0	17
STAT5B	-0.039	0.11	-10000	0	-0.33	17	17
STAT5A	-0.039	0.11	-10000	0	-0.33	17	17
GRB2	0.019	0.003	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.045	0.1	-10000	0	-0.32	16	16
CSN2	0.019	0.07	-10000	0	-10000	0	0
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
LAT	-0.01	0.095	-10000	0	-0.46	8	8
YBX1	0.019	0.006	-10000	0	-10000	0	0
LCK	0.042	0.083	0.25	28	-0.55	1	29
SHC1	0.018	0.004	-10000	0	-10000	0	0
NOX4	-0.035	0.15	-10000	0	-0.56	19	19

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.007	0.002	-10000	0	-10000	0	0
GNB1/GNG2	0.027	0.078	-10000	0	-0.32	9	9
regulation of S phase of mitotic cell cycle	0	0.067	0.21	1	-0.28	10	11
GNAO1	-0.05	0.19	0.25	1	-0.55	31	32
HRAS	0.016	0.01	-10000	0	-10000	0	0
SHBG/T-DHT	-0.006	0.073	-10000	0	-0.3	14	14
PELP1	0.016	0.01	-10000	0	-10000	0	0
AKT1	-0.007	0.002	-10000	0	-10000	0	0
MAP2K1	-0.015	0.081	0.29	3	-0.27	8	11
T-DHT/AR	0.008	0.094	0.18	20	-0.4	10	30
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.002	-10000	0	-0.008	16	16
GNAI2	0.019	0.003	-10000	0	-10000	0	0
GNAI3	0.019	0.003	-10000	0	-10000	0	0
GNAI1	0.009	0.071	-10000	0	-0.55	4	4
mol:GDP	-0.019	0.096	-10000	0	-0.46	10	10
cell proliferation	-0.025	0.14	0.32	6	-0.43	16	22
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
FOS	-0.046	0.21	0.3	3	-0.81	16	19
mol:Ca2+	-0.013	0.028	-10000	0	-0.069	43	43
MAPK3	-0.018	0.11	0.35	5	-0.31	13	18
MAPK1	-0.01	0.094	0.25	3	-0.43	6	9
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
mol:IP3	0	0.001	-10000	0	-0.005	16	16
cAMP biosynthetic process	-0.01	0.07	-10000	0	-0.29	13	13
GNG2	0.024	0.036	0.25	6	-10000	0	6
potassium channel inhibitor activity	0	0.001	-10000	0	-0.005	16	16
HRAS/GTP	0.02	0.074	-10000	0	-0.29	10	10
actin cytoskeleton reorganization	0.025	0.017	-10000	0	-10000	0	0
SRC	0.016	0.01	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.005	16	16
PI3K	0.025	0.015	0.17	1	-0.14	1	2
apoptosis	0.023	0.14	0.46	16	-0.29	5	21
T-DHT/AR/PELP1	0.015	0.083	-10000	0	-0.35	10	10
HRAS/GDP	-0.022	0.092	-10000	0	-0.44	10	10
CREB1	-0.026	0.15	0.29	5	-0.5	16	21
RAC1-CDC42/GTP	0.031	0.02	-10000	0	-10000	0	0
AR	0.011	0.13	0.25	20	-0.55	10	30
GNB1	0.018	0.006	-10000	0	-10000	0	0
RAF1	-0.009	0.084	0.3	3	-0.28	9	12
RAC1-CDC42/GDP	0.01	0.095	-10000	0	-0.42	10	10
T-DHT/AR/PELP1/Src	0.023	0.08	-10000	0	-0.32	10	10
MAP2K2	-0.016	0.081	0.28	2	-0.27	9	11
T-DHT/AR/PELP1/Src/PI3K	0	0.068	0.21	1	-0.28	10	11
GNAZ	-0.017	0.14	-10000	0	-0.55	16	16
SHBG	-0.008	0.12	-10000	0	-0.55	11	11
Gi family/GNB1/GNG2/GDP	-0.082	0.17	-10000	0	-0.4	46	46
mol:T-DHT	0	0.001	-10000	0	-0.006	5	5
RAC1	0.018	0.006	-10000	0	-10000	0	0
GNRH1	-0.003	0.025	0.14	7	-10000	0	7
Gi family/GTP	-0.047	0.11	-10000	0	-0.26	43	43
CDC42	0.019	0.004	-10000	0	-10000	0	0

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.034	0.019	-10000	0	-10000	0	0
RGS9BP	-0.048	0.18	-10000	0	-0.55	29	29
mol:GTP	0	0	-10000	0	-10000	0	0
GRK1	-0.002	0.032	0.25	3	-10000	0	3
mol:Na +	0.037	0.045	-10000	0	-10000	0	0
mol:ADP	-0.014	0.018	0.14	3	-10000	0	3
GNAT2	0.013	0.014	-10000	0	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.058	0.17	-10000	0	-0.37	56	56
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.022	0.006	-10000	0	-10000	0	0
GRK7	-0.016	0.003	-10000	0	-10000	0	0
CNGB3	0.009	0.057	0.25	12	-10000	0	12
Cone Metarhodopsin II/X-Arrestin	0.011	0.002	-10000	0	-10000	0	0
mol:Ca2+	0.01	0.065	0.23	13	-10000	0	13
Cone PDE6	-0.043	0.15	-10000	0	-0.33	54	54
Cone Metarhodopsin II	0.02	0.017	0.16	3	-10000	0	3
Na + (4 Units)	0.051	0.061	0.31	5	-10000	0	5
GNAT2/GDP	-0.044	0.15	-10000	0	-0.32	56	56
GNB5	0.019	0.004	-10000	0	-10000	0	0
mol:GMP (4 units)	-0.017	0.007	-10000	0	-10000	0	0
Cone Transducin	0.037	0.02	-10000	0	-10000	0	0
SLC24A2	0.023	0.07	0.25	20	-10000	0	20
GNB3/GNGT2	0.03	0.021	-10000	0	-10000	0	0
GNB3	0.018	0.004	-10000	0	-10000	0	0
GNAT2/GTP	0.014	0.002	-10000	0	-10000	0	0
CNGA3	0.027	0.062	0.25	17	-10000	0	17
ARR3	-0.016	0.003	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
cGMP/Cone CNG Channel	0.038	0.046	-10000	0	-10000	0	0
mol:Pi	-0.058	0.17	-10000	0	-0.37	56	56
Cone CNG Channel	0.043	0.041	-10000	0	-10000	0	0
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	0.022	0.07	0.25	20	-10000	0	20
RGS9	-0.061	0.2	-10000	0	-0.55	36	36
PDE6C	-0.016	0.004	-10000	0	-10000	0	0
GNGT2	0.024	0.033	0.25	5	-10000	0	5
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	-0.016	0.004	-10000	0	-10000	0	0

×

Glypican 1 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
GPC1/FGF2 dimer/FGFR1 dimer	0.025	0.057	-10000	0	-0.35	5	5
fibroblast growth factor receptor signaling pathway	0.025	0.057	-10000	0	-0.35	5	5
LAMA1	0.016	0.1	0.25	12	-0.55	6	18
PRNP	0.018	0.005	-10000	0	-10000	0	0
GPC1/SLIT2	0.002	0.1	-10000	0	-0.39	15	15
SMAD2	-0.01	0.037	-10000	0	-10000	0	0
GPC1/PrPc/Cu2+	0.023	0.017	0.17	2	-10000	0	2
GPC1/Laminin alpha1	0.022	0.077	0.19	13	-0.4	6	19
TDGF1	-0.012	0.11	0.25	2	-0.55	9	11
CRIPTO/GPC1	0.011	0.083	-10000	0	-0.38	10	10
APP/GPC1	0.023	0.033	0.19	2	-0.41	1	3
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.025	0.064	-10000	0	-0.35	9	9
FLT1	0.017	0.006	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	0.034	0.02	-10000	0	-10000	0	0
SERPINC1	-0.002	0.1	0.25	1	-0.55	8	9
FYN	-0.024	0.066	0.2	1	-0.35	9	10
FGR	-0.024	0.065	0.2	1	-0.35	9	10
positive regulation of MAPKKK cascade	-0.004	0.11	0.26	3	-0.38	11	14
SLIT2	-0.011	0.13	0.25	2	-0.55	14	16
GPC1/NRG	-0.023	0.14	-10000	0	-0.4	30	30
NRG1	-0.047	0.19	0.25	5	-0.55	30	35
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.031	0.022	-10000	0	-10000	0	0
LYN	-0.023	0.062	0.2	1	-0.35	8	9
mol:Spermine	-0.005	0.014	0.14	2	-10000	0	2
cell growth	0.025	0.057	-10000	0	-0.35	5	5
BMP signaling pathway	-0.019	0.022	-10000	0	-0.25	2	2
SRC	-0.023	0.062	0.2	1	-0.35	8	9
TGFBR1	0.019	0.003	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.086	0.27	0.25	37	-0.55	61	98
GPC1	0.019	0.022	0.25	2	-10000	0	2
TGFBR1 (dimer)	0.019	0.003	-10000	0	-10000	0	0
VEGFA	0.018	0.005	-10000	0	-10000	0	0
BLK	-0.006	0.083	0.27	2	-0.35	8	10
HCK	-0.017	0.074	0.2	1	-0.35	9	10
FGF2	0.008	0.079	-10000	0	-0.55	5	5
FGFR1	0.018	0.005	-10000	0	-10000	0	0
VEGFR1 homodimer	0.017	0.006	-10000	0	-10000	0	0
TGFBR2	0.019	0.003	-10000	0	-10000	0	0
cell death	0.023	0.033	0.19	2	-0.41	1	3
ATIII/GPC1	0.012	0.078	-10000	0	-0.4	8	8
PLA2G2A/GPC1	-0.057	0.2	0.19	37	-0.39	64	101
LCK	-0.009	0.086	0.2	1	-0.35	10	11
neuron differentiation	-0.023	0.14	-10000	0	-0.4	30	30
PrPc/Cu2+	0.013	0.004	-10000	0	-10000	0	0
APP	0.016	0.036	-10000	0	-0.55	1	1
TGFBR2 (dimer)	0.019	0.003	-10000	0	-10000	0	0

×

FoxO family 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	-0.4	0.61	-10000	0	-1.3	76	76
PLK1	0.19	0.2	0.53	30	-10000	0	30
CDKN1B	0.024	0.17	0.38	7	-0.37	6	13
FOXO3	0.16	0.17	0.46	34	-10000	0	34
KAT2B	0.046	0.028	-10000	0	-10000	0	0
FOXO1/SIRT1	-0.12	0.19	0.25	1	-0.4	76	77
CAT	0.14	0.16	0.52	7	-10000	0	7
CTNNB1	0.019	0.003	-10000	0	-10000	0	0
AKT1	0.022	0.047	-10000	0	-10000	0	0
FOXO1	-0.12	0.21	0.32	1	-0.43	76	77
MAPK10	-0.068	0.13	0.18	6	-0.29	62	68
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	-0.018	0.094	0.28	1	-0.38	1	2
response to oxidative stress	0.013	0.038	-10000	0	-10000	0	0
FOXO3A/SIRT1	0.11	0.14	0.4	23	-10000	0	23
XPO1	0.019	0.003	-10000	0	-10000	0	0
EP300	-0.007	0.041	-10000	0	-10000	0	0
BCL2L11	0.054	0.064	-10000	0	-0.52	1	1
FOXO1/SKP2	-0.1	0.19	0.25	1	-0.4	67	68
mol:GDP	0.013	0.038	-10000	0	-10000	0	0
RAN	0.019	0.004	-10000	0	-10000	0	0
GADD45A	0.059	0.17	-10000	0	-0.69	4	4
YWHAQ	0.019	0.004	-10000	0	-10000	0	0
FOXO1/14-3-3 family	-0.028	0.11	-10000	0	-0.44	5	5
MST1	0.042	0.06	-10000	0	-0.55	2	2
CSNK1D	0.018	0.005	-10000	0	-10000	0	0
CSNK1E	0.019	0.004	-10000	0	-10000	0	0
FOXO4/14-3-3 family	-0.019	0.12	-10000	0	-0.44	9	9
YWHAB	0.019	0.004	-10000	0	-10000	0	0
MAPK8	0.011	0.052	0.18	12	-0.29	1	13
MAPK9	0.01	0.046	0.18	12	-10000	0	12
YWHAG	0.018	0.004	-10000	0	-10000	0	0
YWHAE	0.018	0.005	-10000	0	-10000	0	0
YWHAZ	0.018	0.005	-10000	0	-10000	0	0
SIRT1	-0.002	0.026	-10000	0	-10000	0	0
SOD2	0.036	0.16	0.43	6	-0.51	3	9
RBL2	0.061	0.25	0.47	2	-0.7	15	17
RAL/GDP	0.028	0.033	-10000	0	-10000	0	0
CHUK	0.045	0.03	-10000	0	-10000	0	0
Ran/GTP	0.015	0.003	-10000	0	-10000	0	0
CSNK1G2	0.019	0.004	-10000	0	-10000	0	0
RAL/GTP	0.029	0.031	-10000	0	-10000	0	0
CSNK1G1	0.019	0.004	-10000	0	-10000	0	0
FASLG	0.095	0.13	-10000	0	-0.66	1	1
SKP2	0.02	0.026	0.25	3	-10000	0	3
USP7	0.019	0.003	-10000	0	-10000	0	0
IKBKB	0.046	0.029	-10000	0	-10000	0	0
CCNB1	0.15	0.18	0.55	19	-10000	0	19
FOXO1-3a-4/beta catenin	0.028	0.15	0.41	6	-10000	0	6
proteasomal ubiquitin-dependent protein catabolic process	-0.1	0.19	0.25	1	-0.4	67	68
CSNK1A1	0.019	0.003	-10000	0	-10000	0	0
SGK1	0.044	0.03	-10000	0	-10000	0	0
CSNK1G3	0.019	0.003	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.026	0.007	-10000	0	-10000	0	0
ZFAND5	-0.014	0.089	0.4	1	-10000	0	1
SFN	-0.003	0.13	0.25	9	-0.55	13	22
CDK2	-0.021	0.055	-10000	0	-10000	0	0
FOXO3A/14-3-3	0.025	0.11	0.26	2	-0.43	6	8
CREBBP	-0.021	0.055	-10000	0	-10000	0	0
FBXO32	0.15	0.17	0.51	16	-10000	0	16
BCL6	0.12	0.16	0.47	2	-0.72	3	5
RALB	0.019	0.004	-10000	0	-10000	0	0
RALA	0.018	0.006	-10000	0	-10000	0	0
YWHAH	0.018	0.004	-10000	0	-10000	0	0

×

LPA receptor mediated events

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
GNB1/GNG2	0.045	0.062	0.31	1	-0.27	3	4
NF kappa B1 p50/RelA/I kappa B alpha	0.031	0.064	0.29	1	-10000	0	1
AP1	0.023	0.082	0.27	1	-0.28	12	13
mol:PIP3	-0.019	0.04	-10000	0	-0.36	2	2
AKT1	0.001	0.071	0.31	4	-10000	0	4
PTK2B	0.017	0.061	0.25	3	-0.21	2	5
RHOA	0.002	0.062	0.26	1	-0.29	6	7
PIK3CB	0.018	0.006	-10000	0	-10000	0	0
mol:Ca2+	0.006	0.062	0.34	2	-10000	0	2
MAGI3	0.019	0.004	-10000	0	-10000	0	0
RELA	0.019	0.003	-10000	0	-10000	0	0
apoptosis	0.016	0.048	-10000	0	-0.24	4	4
HRAS/GDP	0.014	0.003	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.09	0.14	0.24	2	-0.27	72	74
NF kappa B1 p50/RelA	0.016	0.064	0.27	1	-10000	0	1
endothelial cell migration	0.022	0.11	0.28	23	-0.5	4	27
ADCY4	-0.031	0.1	-10000	0	-0.34	10	10
ADCY5	-0.1	0.18	-10000	0	-0.44	41	41
ADCY6	-0.03	0.1	-10000	0	-0.35	11	11
ADCY7	-0.03	0.1	-10000	0	-0.35	11	11
ADCY1	-0.024	0.1	0.2	1	-0.35	10	11
ADCY2	-0.044	0.13	-10000	0	-0.39	19	19
ADCY3	-0.031	0.1	-10000	0	-0.35	12	12
ADCY8	-0.047	0.12	-10000	0	-0.34	18	18
ADCY9	-0.03	0.1	-10000	0	-0.33	12	12
GSK3B	0.012	0.058	0.23	3	-10000	0	3
arachidonic acid secretion	-0.036	0.11	-10000	0	-0.28	33	33
GNG2	0.023	0.037	0.26	6	-10000	0	6
TRIP6	0.014	0.015	-10000	0	-10000	0	0
GNAO1	-0.036	0.12	0.15	1	-0.32	33	34
HRAS	0.019	0.004	-10000	0	-10000	0	0
NFKBIA	0.016	0.076	0.38	3	-10000	0	3
GAB1	0.019	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	0.005	0.16	-10000	0	-0.82	9	9
JUN	0.018	0.006	-10000	0	-10000	0	0
LPA/LPA2/NHERF2	0.034	0.033	-10000	0	-10000	0	0
TIAM1	-0.006	0.18	-10000	0	-0.94	9	9
PIK3R1	0.019	0.016	0.26	1	-10000	0	1
mol:IP3	0.003	0.053	-10000	0	-10000	0	0
PLCB3	-0.005	0.03	0.22	1	-10000	0	1
FOS	-0.004	0.11	-10000	0	-0.55	10	10
positive regulation of mitosis	-0.036	0.11	-10000	0	-0.28	33	33
LPA/LPA1-2-3	0.054	0.067	0.33	1	-0.25	4	5
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0	-10000	0	-10000	0	0
BCAR1	0.018	0.005	-10000	0	-10000	0	0
stress fiber formation	0.022	0.073	0.27	3	-0.31	4	7
GNAZ	-0.016	0.087	-10000	0	-0.3	18	18
EGFR/PI3K-beta/Gab1	-0.01	0.051	-10000	0	-0.38	2	2
positive regulation of dendritic cell cytokine production	0.052	0.065	0.32	1	-0.25	4	5
LPA/LPA2/MAGI-3	0.034	0.033	0.17	9	-10000	0	9
ARHGEF1	0.008	0.069	0.32	3	-0.29	1	4
GNAI2	0.002	0.053	-10000	0	-0.27	4	4
GNAI3	0.003	0.054	-10000	0	-0.27	4	4
GNAI1	-0.003	0.068	-10000	0	-0.3	8	8
LPA/LPA3	0.023	0.038	0.18	10	-0.12	2	12
LPA/LPA2	0.024	0.036	0.18	9	-0.12	2	11
LPA/LPA1	0.027	0.064	0.18	4	-0.32	4	8
HB-EGF/EGFR	0.049	0.064	0.28	1	-0.35	2	3
HBEGF	0.047	0.084	0.15	98	-0.41	1	99
mol:DAG	0.003	0.053	-10000	0	-10000	0	0
cAMP biosynthetic process	-0.053	0.13	0.22	1	-0.34	33	34
NFKB1	0.019	0.001	-10000	0	-10000	0	0
SRC	0.019	0.004	-10000	0	-10000	0	0
GNB1	0.017	0.007	-10000	0	-10000	0	0
LYN	0.014	0.074	0.33	3	-0.4	1	4
GNAQ	0.014	0.031	0.17	1	-10000	0	1
LPAR2	0.027	0.044	0.26	9	-10000	0	9
LPAR3	0.016	0.051	0.26	10	-10000	0	10
LPAR1	0.025	0.054	0.26	3	-0.31	3	6
IL8	0.058	0.16	0.35	22	-0.5	8	30
PTK2	0.009	0.066	0.29	3	-0.27	2	5
Rac1/GDP	0.013	0.004	-10000	0	-10000	0	0
CASP3	0.015	0.048	-10000	0	-0.24	4	4
EGFR	0.017	0.039	0.25	1	-0.55	1	2
PLCG1	0.009	0.052	0.19	2	-10000	0	2
PLD2	0.01	0.065	0.24	1	-0.27	2	3
G12/G13	0.044	0.053	-10000	0	-0.28	2	2
PI3K-beta	-0.016	0.046	-10000	0	-10000	0	0
cell migration	0.015	0.061	0.22	1	-0.25	9	10
SLC9A3R2	0.019	0.003	-10000	0	-10000	0	0
PXN	0.022	0.073	0.27	3	-0.31	4	7
HRAS/GTP	-0.04	0.11	-10000	0	-0.29	33	33
RAC1	0.018	0.006	-10000	0	-10000	0	0
MMP9	0.11	0.12	0.26	100	-0.55	1	101
PRKCE	0.018	0.006	-10000	0	-10000	0	0
PRKCD	0.005	0.064	0.33	3	-10000	0	3
Gi(beta/gamma)	-0.023	0.1	-10000	0	-0.34	11	11
mol:LPA	0.006	0.028	-10000	0	-0.16	3	3
TRIP6/p130 Cas/FAK1/Paxillin	0.029	0.066	-10000	0	-0.48	1	1
MAPKKK cascade	-0.036	0.11	-10000	0	-0.28	33	33
contractile ring contraction involved in cytokinesis	0.004	0.064	0.26	1	-0.28	6	7
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.006	0.079	0.17	1	-0.29	16	17
GNA15	0.016	0.035	0.19	2	-10000	0	2
GNA12	0.018	0.005	-10000	0	-10000	0	0
GNA13	0.019	0.004	-10000	0	-10000	0	0
MAPT	-0.093	0.14	0.24	2	-0.28	72	74
GNA11	0.013	0.037	0.17	1	-0.31	1	2
Rac1/GTP	0.004	0.17	-10000	0	-0.87	9	9
MMP2	0.022	0.11	0.28	23	-0.51	4	27

×

Plasma membrane estrogen receptor signaling

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
GNB1/GNG2	0.042	0.066	0.31	1	-0.3	5	6
ER alpha/Gai/GDP/Gbeta gamma	-0.078	0.19	-10000	0	-0.41	46	46
AKT1	-0.022	0.18	-10000	0	-0.8	12	12
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.019	0.19	-10000	0	-0.79	13	13
mol:Ca2+	-0.02	0.091	-10000	0	-0.38	13	13
IGF1R	0.014	0.05	-10000	0	-0.55	2	2
E2/ER alpha (dimer)/Striatin	0.023	0.068	0.17	15	-0.35	6	21
SHC1	0.018	0.004	-10000	0	-10000	0	0
apoptosis	0.02	0.17	0.76	12	-10000	0	12
RhoA/GTP	-0.023	0.044	-10000	0	-0.28	6	6
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.044	0.16	-10000	0	-0.46	18	18
regulation of stress fiber formation	0.012	0.06	0.24	3	-0.19	2	5
E2/ERA-ERB (dimer)	0.026	0.067	-10000	0	-0.35	5	5
KRAS	0.018	0.004	-10000	0	-10000	0	0
G13/GTP	0.023	0.062	-10000	0	-0.32	6	6
pseudopodium formation	-0.012	0.06	0.19	2	-0.24	3	5
E2/ER alpha (dimer)/PELP1	0.023	0.067	0.17	15	-0.34	6	21
GRB2	0.019	0.003	-10000	0	-10000	0	0
GNG2	0.024	0.036	0.25	6	-10000	0	6
GNAO1	-0.05	0.19	0.25	1	-0.55	31	32
HRAS	0.019	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.037	0.16	0.27	1	-0.52	15	16
E2/ER beta (dimer)	0.018	0.025	0.18	6	-10000	0	6
mol:GDP	0.006	0.078	0.26	2	-0.4	6	8
mol:NADP	-0.037	0.16	0.27	1	-0.52	15	16
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
mol:IP3	-0.021	0.094	-10000	0	-0.39	13	13
IGF-1R heterotetramer	0.014	0.05	-10000	0	-0.55	2	2
PLCB1	-0.016	0.1	-10000	0	-0.4	15	15
PLCB2	-0.014	0.1	-10000	0	-0.4	14	14
IGF1	0.019	0.075	0.25	8	-0.55	3	11
mol:L-citrulline	-0.037	0.16	0.27	1	-0.52	15	16
RHOA	0.019	0.004	-10000	0	-10000	0	0
Gai/GDP	-0.14	0.29	-10000	0	-0.66	57	57
JNK cascade	0.018	0.025	0.17	6	-10000	0	6
BCAR1	0.018	0.005	-10000	0	-10000	0	0
ESR2	0.024	0.036	0.25	6	-10000	0	6
GNAQ	0.019	0.003	-10000	0	-10000	0	0
ESR1	0.02	0.11	0.25	17	-0.55	6	23
Gq family/GDP/Gbeta gamma	-0.015	0.1	-10000	0	-0.54	2	2
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.005	0.072	-10000	0	-0.48	2	2
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.044	0.16	-10000	0	-0.47	18	18
GNAZ	-0.017	0.14	-10000	0	-0.55	16	16
E2/ER alpha (dimer)	0.014	0.076	0.18	17	-0.4	6	23
STRN	0.02	0.015	0.25	1	-10000	0	1
GNAL	-0.001	0.11	0.25	3	-0.55	10	13
PELP1	0.018	0.005	-10000	0	-10000	0	0
MAPK11	-0.007	0.023	0.18	2	-10000	0	2
GNAI2	0.019	0.003	-10000	0	-10000	0	0
GNAI3	0.019	0.003	-10000	0	-10000	0	0
GNAI1	0.009	0.071	-10000	0	-0.55	4	4
HBEGF	-0.043	0.19	0.32	6	-0.49	21	27
cAMP biosynthetic process	0.007	0.078	-10000	0	-0.28	15	15
SRC	-0.074	0.18	0.25	1	-0.52	22	23
PI3K	0.028	0.017	-10000	0	-0.17	1	1
GNB1	0.018	0.006	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	0.026	0.072	-10000	0	-0.39	5	5
SOS1	0.019	0.004	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.056	0.13	-10000	0	-0.42	17	17
Gs family/GTP	0.012	0.083	-10000	0	-0.29	15	15
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.033	0.012	-10000	0	-10000	0	0
vasodilation	-0.034	0.15	0.26	1	-0.49	15	16
mol:DAG	-0.021	0.094	-10000	0	-0.39	13	13
Gs family/GDP/Gbeta gamma	-0.003	0.08	-10000	0	-0.3	14	14
MSN	-0.013	0.063	0.19	2	-0.26	3	5
Gq family/GTP	-0.013	0.11	-10000	0	-0.42	16	16
mol:PI-3-4-5-P3	-0.017	0.18	-10000	0	-0.76	13	13
NRAS	0.019	0.003	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.034	0.15	0.49	15	-0.26	1	16
GRB2/SOS1	0.027	0.007	-10000	0	-10000	0	0
RhoA/GDP	0.015	0.077	0.25	2	-0.38	6	8
NOS3	-0.039	0.17	0.27	1	-0.55	15	16
GNA11	0.017	0.036	-10000	0	-0.55	1	1
MAPKKK cascade	-0.025	0.15	-10000	0	-0.61	11	11
E2/ER alpha (dimer)/PELP1/Src	-0.046	0.17	0.24	1	-0.46	20	21
ruffle organization	-0.012	0.06	0.19	2	-0.24	3	5
ROCK2	-0.008	0.072	0.24	3	-0.27	5	8
GNA14	-0.017	0.14	-10000	0	-0.55	16	16
GNA15	0.024	0.033	0.25	5	-10000	0	5
GNA13	0.019	0.004	-10000	0	-10000	0	0
MMP9	-0.04	0.19	0.31	9	-0.49	21	30
MMP2	-0.064	0.18	0.25	1	-0.5	22	23

×

Class IB PI3K non-lipid kinase 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
cAMP biosynthetic process	0.003	0.11	0.55	10	-10000	0	10
PI3K Class IB/PDE3B	-0.003	0.11	-10000	0	-0.55	10	10
PDE3B	-0.003	0.11	-10000	0	-0.55	10	10

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	-0.014	0.006	-10000	0	-10000	0	0
SMARCC1	-0.013	0.026	-10000	0	-10000	0	0
REL	0.02	0.009	-10000	0	-10000	0	0
HDAC7	-0.15	0.14	0.3	2	-0.37	31	33
JUN	0.015	0.011	-10000	0	-10000	0	0
EP300	0.018	0.004	-10000	0	-10000	0	0
KAT2B	0.018	0.004	-10000	0	-10000	0	0
KAT5	0.019	0.004	-10000	0	-10000	0	0
MAPK14	-0.051	0.074	-10000	0	-0.44	8	8
FOXO1	0.014	0.012	-10000	0	-10000	0	0
T-DHT/AR	-0.16	0.15	0.31	2	-0.38	34	36
MAP2K6	-0.04	0.099	-10000	0	-0.57	8	8
BRM/BAF57	0.018	0.025	-10000	0	-10000	0	0
MAP2K4	-0.02	0.024	-10000	0	-10000	0	0
SMARCA2	0.012	0.017	-10000	0	-10000	0	0
PDE9A	-0.35	0.48	-10000	0	-1.2	64	64
NCOA2	0.01	0.068	0.25	8	-0.55	2	10
CEBPA	0.02	0.022	0.25	2	-10000	0	2
EHMT2	0.014	0.012	-10000	0	-10000	0	0
cell proliferation	-0.16	0.16	0.35	2	-0.42	23	25
NR0B1	0.017	0.06	0.25	14	-10000	0	14
EGR1	0.007	0.063	-10000	0	-0.55	3	3
RXRs/9cRA	0.022	0.085	-10000	0	-0.32	10	10
AR/RACK1/Src	-0.1	0.11	-10000	0	-0.37	12	12
AR/GR	-0.03	0.094	0.23	3	-0.31	13	16
GNB2L1	0.008	0.018	-10000	0	-10000	0	0
PKN1	0.018	0.005	-10000	0	-10000	0	0
RCHY1	0.019	0.003	-10000	0	-10000	0	0
epidermal growth factor receptor activity	-0.002	0.004	-10000	0	-0.015	5	5
MAPK8	-0.035	0.034	-10000	0	-0.44	1	1
T-DHT/AR/TIF2/CARM1	-0.082	0.12	0.3	4	-0.41	9	13
SRC	-0.067	0.068	-10000	0	-0.36	6	6
NR3C1	0.019	0.003	-10000	0	-10000	0	0
KLK3	-0.16	0.38	-10000	0	-1.2	29	29
APPBP2	-0.016	0.025	-10000	0	-10000	0	0
TRIM24	0.013	0.017	-10000	0	-10000	0	0
T-DHT/AR/TIP60	-0.071	0.1	0.32	3	-0.4	7	10
TMPRSS2	-0.64	0.55	-10000	0	-1.1	143	143
RXRG	0.013	0.14	0.25	25	-0.55	10	35
mol:9cRA	-0.001	0.002	-10000	0	-10000	0	0
RXRA	0.015	0.012	-10000	0	-10000	0	0
RXRB	0.014	0.013	-10000	0	-10000	0	0
CARM1	0.008	0.018	-10000	0	-10000	0	0
NR2C2	0.015	0.012	-10000	0	-10000	0	0
KLK2	-0.22	0.3	0.28	2	-0.67	75	77
AR	-0.047	0.082	-10000	0	-0.32	16	16
SENP1	0.015	0.011	-10000	0	-10000	0	0
HSP90AA1	0.019	0.004	-10000	0	-10000	0	0
MDM2	0.017	0.014	-10000	0	-10000	0	0
SRY	0.003	0.01	0.031	28	-0.027	2	30
GATA2	0.017	0.054	0.25	2	-0.55	2	4
MYST2	0	0.001	-10000	0	-10000	0	0
HOXB13	-0.044	0.2	0.25	20	-0.55	30	50
T-DHT/AR/RACK1/Src	-0.083	0.11	0.3	2	-0.41	7	9
positive regulation of transcription	0.017	0.054	0.25	2	-0.55	2	4
DNAJA1	-0.015	0.025	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.006	0.005	-10000	0	-10000	0	0
NCOA1	0.018	0.02	-10000	0	-10000	0	0
SPDEF	0.012	0.032	0.24	3	-10000	0	3
T-DHT/AR/TIF2	-0.043	0.095	0.24	4	-0.36	6	10
T-DHT/AR/Hsp90	-0.07	0.1	0.29	4	-0.4	7	11
GSK3B	-0.011	0.018	-10000	0	-10000	0	0
NR2C1	0.019	0.006	-10000	0	-10000	0	0
mol:T-DHT	-0.07	0.069	-10000	0	-0.36	7	7
SIRT1	0.018	0.005	-10000	0	-10000	0	0
ZMIZ2	0.021	0.013	-10000	0	-10000	0	0
POU2F1	-0.07	0.076	-10000	0	-0.19	31	31
T-DHT/AR/DAX-1	-0.064	0.11	0.31	4	-0.39	7	11
CREBBP	0.019	0.003	-10000	0	-10000	0	0
SMARCE1	0.013	0.017	-10000	0	-10000	0	0

×

ErbB4 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
ErbB4/ErbB4/HBEGF/HBEGF	-0.024	0.085	-10000	0	-10000	0	0
epithelial cell differentiation	-0.022	0.1	-10000	0	-0.37	3	3
ITCH	0.028	0.02	-10000	0	-10000	0	0
WWP1	-0.024	0.077	-10000	0	-10000	0	0
FYN	0.018	0.005	-10000	0	-10000	0	0
EGFR	0.016	0.039	0.25	1	-0.55	1	2
PRL	0.048	0.096	0.25	44	-10000	0	44
neuron projection morphogenesis	-0.049	0.12	0.31	3	-0.37	7	10
PTPRZ1	0.031	0.11	0.25	30	-0.55	4	34
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.039	0.12	-10000	0	-0.39	7	7
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.06	0.12	-10000	0	-0.35	27	27
ADAM17	0.027	0.02	-10000	0	-10000	0	0
ErbB4/ErbB4	-0.038	0.082	-10000	0	-0.31	2	2
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.024	0.086	-10000	0	-10000	0	0
NCOR1	0.017	0.007	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.049	0.12	-10000	0	-0.34	23	23
GRIN2B	-0.057	0.11	0.25	2	-0.38	9	11
ErbB4/ErbB2/betacellulin	-0.052	0.12	-10000	0	-0.34	25	25
STAT1	0.02	0.015	0.25	1	-10000	0	1
HBEGF	0.019	0.003	-10000	0	-10000	0	0
PRLR	-0.012	0.15	0.25	10	-0.55	17	27
E4ICDs/ETO2	-0.021	0.089	-10000	0	-10000	0	0
axon guidance	-0.035	0.074	-10000	0	-10000	0	0
NEDD4	0.029	0.02	-10000	0	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	0.022	0.13	0.36	5	-0.4	17	22
CBFA2T3	0.024	0.036	0.25	6	-10000	0	6
ErbB4/ErbB2/HBEGF	-0.025	0.085	-10000	0	-0.32	8	8
MAPK3	-0.053	0.11	0.25	1	-0.37	7	8
STAT1 (dimer)	-0.025	0.085	-10000	0	-10000	0	0
MAPK1	-0.051	0.11	0.25	1	-0.37	7	8
JAK2	0.019	0.016	0.25	1	-10000	0	1
ErbB4/ErbB2/neuregulin 1 beta	-0.07	0.12	-10000	0	-0.34	33	33
NRG1	-0.047	0.14	-10000	0	-0.41	30	30
NRG3	0.01	0.031	0.25	3	-10000	0	3
NRG2	-0.016	0.13	-10000	0	-0.55	15	15
NRG4	0.018	0.036	0.25	5	-10000	0	5
heart development	-0.035	0.074	-10000	0	-10000	0	0
neural crest cell migration	-0.07	0.12	-10000	0	-0.34	33	33
ERBB2	-0.015	0.073	-10000	0	-0.41	8	8
WWOX/E4ICDs	-0.025	0.084	-10000	0	-10000	0	0
SHC1	0.018	0.004	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.014	0.088	-10000	0	-10000	0	0
apoptosis	0.027	0.095	0.41	6	-10000	0	6
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.043	0.12	-10000	0	-0.38	12	12
ErbB4/ErbB2/epiregulin	-0.015	0.092	0.34	1	-0.33	4	5
ErbB4/ErbB4/betacellulin/betacellulin	-0.055	0.13	-10000	0	-0.38	19	19
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.002	0.13	0.31	2	-0.42	5	7
MDM2	0.01	0.12	0.25	38	-10000	0	38
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.046	0.11	-10000	0	-0.33	27	27
STAT5A	-0.038	0.071	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.049	0.12	-10000	0	-0.34	23	23
DLG4	0.018	0.005	-10000	0	-10000	0	0
GRB2/SHC	0.027	0.008	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.02	0.073	-10000	0	-10000	0	0
STAT5A (dimer)	-0.017	0.12	-10000	0	-0.41	2	2
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.029	0.079	-10000	0	-10000	0	0
LRIG1	0.017	0.036	-10000	0	-0.55	1	1
EREG	0.03	0.067	0.25	20	-10000	0	20
BTC	-0.036	0.16	0.25	3	-0.55	22	25
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.036	0.073	-10000	0	-10000	0	0
ERBB4	-0.038	0.082	-10000	0	-0.31	2	2
STAT5B	0.019	0.002	-10000	0	-10000	0	0
YAP1	-0.015	0.093	-10000	0	-0.45	10	10
GRB2	0.019	0.003	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.025	0.089	-10000	0	-0.32	8	8
glial cell differentiation	0.02	0.072	-10000	0	-10000	0	0
WWOX	0.018	0.006	-10000	0	-10000	0	0
cell proliferation	-0.092	0.15	-10000	0	-0.42	22	22

×

PLK2 and PLK4 events

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.Total.Perturbations
PLK2	0.019	0.002	-10000	0	-9999	0
PLK4	0.032	0.054	0.25	14	-9999	14
regulation of centriole replication	-0.006	0.036	0.14	14	-9999	14

×

Glucocorticoid receptor regulatory network

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
PCK2	-0.008	0.094	-10000	0	-0.39	3	3
SMARCC2	0.019	0.004	-10000	0	-10000	0	0
SMARCC1	0.019	0.003	-10000	0	-10000	0	0
TBX21	0.049	0.16	0.35	38	-0.38	5	43
SUMO2	0.019	0.008	-10000	0	-10000	0	0
STAT1 (dimer)	0.022	0.015	0.26	1	-10000	0	1
FKBP4	0.018	0.005	-10000	0	-10000	0	0
FKBP5	0.024	0.036	0.25	6	-10000	0	6
GR alpha/HSP90/FKBP51/HSP90	0.009	0.1	0.33	5	-10000	0	5
PRL	0.052	0.14	0.45	2	-10000	0	2
cortisol/GR alpha (dimer)/TIF2	-0.007	0.22	0.54	12	-0.51	6	18
RELA	-0.016	0.099	-10000	0	-0.28	16	16
FGG	-0.016	0.2	0.5	8	-0.43	5	13
GR beta/TIF2	-0.001	0.12	0.31	8	-0.54	2	10
IFNG	0.069	0.25	0.49	22	-0.59	6	28
apoptosis	-0.059	0.15	0.46	4	-0.56	3	7
CREB1	-0.028	0.13	-10000	0	-0.4	29	29
histone acetylation	-0.033	0.11	0.28	2	-0.34	8	10
BGLAP	0.014	0.1	-10000	0	-10000	0	0
GR/PKAc	0.011	0.091	0.28	1	-10000	0	1
NF kappa B1 p50/RelA	-0.032	0.18	0.35	2	-0.4	40	42
SMARCD1	0.019	0.004	-10000	0	-10000	0	0
MDM2	0.009	0.085	0.28	12	-10000	0	12
GATA3	-0.027	0.16	-10000	0	-0.55	21	21
AKT1	0.017	0.004	-10000	0	-10000	0	0
CSF2	-0.023	0.093	-10000	0	-10000	0	0
GSK3B	0.019	0.008	-10000	0	-10000	0	0
NR1I3	-0.046	0.16	0.56	3	-0.8	3	6
CSN2	-0.024	0.17	0.4	6	-0.39	6	12
BRG1/BAF155/BAF170/BAF60A	0.045	0.018	-10000	0	-10000	0	0
NFATC1	0.019	0.015	0.25	1	-10000	0	1
POU2F1	0.036	0.04	0.25	1	-10000	0	1
CDKN1A	-0.02	0.084	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.001	0.004	-10000	0	-10000	0	0
SFN	-0.003	0.13	0.25	9	-0.55	13	22
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.001	0.12	0.34	4	-0.3	10	14
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.052	0.16	0.44	2	-0.82	4	6
JUN	0.056	0.17	0.38	24	-0.4	4	28
IL4	0.005	0.11	-10000	0	-0.38	3	3
CDK5R1	0.025	0.039	0.26	7	-10000	0	7
PRKACA	0.018	0.005	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.033	0.087	0.22	5	-0.37	8	13
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.011	0.095	0.32	3	-10000	0	3
cortisol/GR alpha (monomer)	-0.01	0.25	0.59	14	-0.47	7	21
NCOA2	0.021	0.066	0.25	8	-0.55	2	10
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	0.02	0.14	0.23	6	-0.51	11	17
AP-1/NFAT1-c-4	0.063	0.25	0.45	18	-0.55	10	28
AFP	0.038	0.14	0.41	2	-10000	0	2
SUV420H1	0.019	0.003	-10000	0	-10000	0	0
IRF1	0	0.13	0.43	2	-10000	0	2
TP53	0.02	0.009	-10000	0	-10000	0	0
PPP5C	0.018	0.005	-10000	0	-10000	0	0
KRT17	-0.041	0.41	0.47	11	-1.2	26	37
KRT14	0.066	0.17	0.46	1	-10000	0	1
TBP	0.021	0.009	-10000	0	-10000	0	0
CREBBP	-0.02	0.062	-10000	0	-10000	0	0
HDAC1	0.019	0.004	-10000	0	-10000	0	0
HDAC2	0.016	0.01	-10000	0	-10000	0	0
AP-1	0.064	0.25	0.45	18	-0.55	10	28
MAPK14	0.018	0.008	-10000	0	-10000	0	0
MAPK10	-0.14	0.26	-10000	0	-0.55	72	72
MAPK11	0.019	0.017	0.25	1	-10000	0	1
KRT5	0.046	0.23	0.48	16	-0.63	3	19
interleukin-1 receptor activity	-0.001	0.004	-10000	0	-10000	0	0
NCOA1	0.019	0.004	-10000	0	-10000	0	0
STAT1	0.022	0.015	0.26	1	-10000	0	1
CGA	-0.12	0.39	-10000	0	-1.1	31	31
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	-0.046	0.11	0.33	2	-0.35	2	4
MAPK3	0.018	0.009	-10000	0	-10000	0	0
MAPK1	0.018	0.009	-10000	0	-10000	0	0
ICAM1	-0.025	0.19	0.52	1	-0.53	11	12
NFKB1	-0.02	0.1	-10000	0	-0.28	19	19
MAPK8	0.038	0.15	0.33	13	-0.4	6	19
MAPK9	0.018	0.007	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.061	0.16	0.47	4	-0.58	3	7
BAX	-0.022	0.081	-10000	0	-10000	0	0
POMC	-0.035	0.27	0.45	2	-1.2	9	11
EP300	-0.02	0.062	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/p53	-0.02	0.2	0.53	7	-0.43	5	12
proteasomal ubiquitin-dependent protein catabolic process	0.001	0.069	0.24	10	-10000	0	10
SGK1	-0.016	0.081	-10000	0	-10000	0	0
IL13	-0.016	0.23	0.47	1	-0.77	7	8
IL6	-0.1	0.39	0.41	4	-1.1	30	34
PRKACG	-0.016	0.003	-10000	0	-10000	0	0
IL5	-0.013	0.2	-10000	0	-0.67	5	5
IL2	0.027	0.2	-10000	0	-0.57	5	5
CDK5	0.018	0.008	-10000	0	-10000	0	0
PRKACB	0.018	0.004	-10000	0	-10000	0	0
HSP90AA1	0.019	0.004	-10000	0	-10000	0	0
IL8	-0.036	0.27	0.43	7	-0.83	14	21
CDK5R1/CDK5	0.031	0.029	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	-0.004	0.15	0.34	1	-0.4	16	17
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	-0.001	0.2	0.48	13	-0.4	5	18
SMARCA4	0.018	0.005	-10000	0	-10000	0	0
chromatin remodeling	0.004	0.13	0.38	7	-10000	0	7
NF kappa B1 p50/RelA/Cbp	-0.052	0.16	-10000	0	-0.44	19	19
JUN (dimer)	0.056	0.17	0.37	24	-0.4	4	28
YWHAH	0.018	0.004	-10000	0	-10000	0	0
VIPR1	-0.051	0.26	0.54	1	-0.86	22	23
NR3C1	-0.011	0.15	0.43	8	-0.32	1	9
NR4A1	-0.023	0.15	-10000	0	-0.53	20	20
TIF2/SUV420H1	0.028	0.049	-10000	0	-0.41	2	2
MAPKKK cascade	-0.059	0.15	0.46	4	-0.56	3	7
cortisol/GR alpha (dimer)/Src-1	-0.006	0.22	0.51	14	-0.42	6	20
PBX1	0.011	0.12	-10000	0	-0.55	11	11
POU1F1	0.029	0.05	0.26	3	-10000	0	3
SELE	-0.14	0.43	0.41	2	-1.1	39	41
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.004	0.13	0.38	7	-10000	0	7
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	-0.001	0.2	0.48	13	-0.4	5	18
mol:cortisol	-0.012	0.14	0.34	14	-0.24	10	24
MMP1	0.048	0.27	0.46	6	-0.99	11	17

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.005	0.068	-10000	0	-10000	0	0
VDR	-0.022	0.14	-10000	0	-0.55	18	18
FAM120B	0.018	0.004	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.018	0.07	0.25	2	-0.26	9	11
RXRs/LXRs/DNA/Oxysterols	0.018	0.069	0.3	2	-10000	0	2
MED1	0.019	0.002	-10000	0	-10000	0	0
mol:9cRA	0.003	0.008	-10000	0	-10000	0	0
RARs/THRs/DNA/Src-1	-0.011	0.075	-10000	0	-0.26	16	16
RXRs/NUR77	0.023	0.12	0.28	1	-0.32	22	23
RXRs/PPAR	0.002	0.074	-10000	0	-0.27	8	8
NCOR2	0.019	0.004	-10000	0	-10000	0	0
VDR/VDR/Vit D3	-0.016	0.11	-10000	0	-0.4	18	18
RARs/VDR/DNA/Vit D3	0.011	0.098	-10000	0	-0.3	22	22
RARA	0.019	0.002	-10000	0	-10000	0	0
NCOA1	0.019	0.004	-10000	0	-10000	0	0
VDR/VDR/DNA	-0.022	0.14	-10000	0	-0.55	18	18
RARs/RARs/DNA/9cRA	0.029	0.044	-10000	0	-0.3	4	4
RARG	0.02	0.015	0.25	1	-10000	0	1
RPS6KB1	0.007	0.077	0.54	5	-10000	0	5
RARs/THRs/DNA/SMRT	-0.01	0.075	-10000	0	-0.26	16	16
THRA	0.019	0.002	-10000	0	-10000	0	0
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	-0.016	0.11	-10000	0	-0.4	18	18
RXRs/PPAR/9cRA/PGJ2/DNA	0.039	0.088	0.28	2	-0.31	10	12
NR1H4	-0.1	0.22	0.25	3	-0.55	51	54
RXRs/LXRs/DNA	0.055	0.092	0.35	1	-0.31	9	10
NR1H2	0.022	0.008	-10000	0	-10000	0	0
NR1H3	0.022	0.009	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.016	0.11	0.26	1	-0.28	25	26
NR4A1	-0.013	0.13	-10000	0	-0.55	14	14
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.047	0.12	-10000	0	-0.26	51	51
RXRG	0.021	0.14	0.26	25	-0.55	10	35
RXR alpha/CCPG	0.028	0.01	-10000	0	-10000	0	0
RXRA	0.021	0.009	-10000	0	-10000	0	0
RXRB	0.021	0.01	-10000	0	-10000	0	0
THRB	-0.008	0.12	-10000	0	-0.55	12	12
PPARG	0.022	0.03	0.25	4	-10000	0	4
PPARD	0.018	0.005	-10000	0	-10000	0	0
TNF	0.019	0.076	0.36	1	-10000	0	1
mol:Oxysterols	0.003	0.007	-10000	0	-10000	0	0
cholesterol transport	0.018	0.069	0.3	2	-10000	0	2
PPARA	0.016	0.036	-10000	0	-0.55	1	1
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.01	0.071	-10000	0	-0.55	4	4
RXRs/NUR77/BCL2	-0.006	0.083	-10000	0	-0.26	20	20
SREBF1	0.015	0.069	0.48	1	-10000	0	1
RXRs/RXRs/DNA/9cRA	0.039	0.088	0.28	2	-0.31	10	12
ABCA1	0.015	0.07	0.47	1	-10000	0	1
RARs/THRs	0.031	0.09	-10000	0	-0.31	16	16
RXRs/FXR	-0.029	0.16	0.28	1	-0.32	54	55
BCL2	0.018	0.004	-10000	0	-10000	0	0

×

Ephrin B reverse signaling

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
EFNB2	0.017	0.006	-10000	0	-10000	0	0
EPHB2	0.048	0.079	0.26	32	-10000	0	32
EFNB1	-0.011	0.016	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.065	0.067	0.32	6	-10000	0	6
Ephrin B2/EPHB1-2	0.055	0.059	0.31	2	-10000	0	2
neuron projection morphogenesis	0.043	0.047	0.28	3	-10000	0	3
Ephrin B1/EPHB1-2/Tiam1	0.071	0.075	0.33	9	-10000	0	9
DNM1	0.021	0.021	0.25	2	-10000	0	2
cell-cell signaling	0	0.003	-10000	0	-10000	0	0
MAP2K4	-0.011	0.14	0.33	2	-0.51	15	17
YES1	-0.039	0.19	-10000	0	-0.78	16	16
Ephrin B1/EPHB1-2/NCK2	0.069	0.071	0.31	9	-10000	0	9
PI3K	-0.002	0.14	-10000	0	-0.55	16	16
mol:GDP	0.069	0.073	0.32	9	-10000	0	9
ITGA2B	0.024	0.036	0.25	6	-10000	0	6
endothelial cell proliferation	0.022	0.01	-10000	0	-10000	0	0
FYN	-0.036	0.19	-10000	0	-0.77	16	16
MAP3K7	-0.032	0.14	-10000	0	-0.57	16	16
FGR	-0.035	0.19	-10000	0	-0.76	16	16
TIAM1	0.024	0.036	0.25	6	-10000	0	6
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
RGS3	0.019	0.003	-10000	0	-10000	0	0
cell adhesion	-0.018	0.14	-10000	0	-0.53	15	15
LYN	-0.036	0.19	-10000	0	-0.76	16	16
Ephrin B1/EPHB1-2/Src Family Kinases	-0.036	0.18	-10000	0	-0.7	16	16
Ephrin B1/EPHB1-2	-0.029	0.15	-10000	0	-0.64	14	14
SRC	-0.036	0.19	-10000	0	-0.76	16	16
ITGB3	0.008	0.079	-10000	0	-0.55	5	5
EPHB1	0.045	0.072	0.25	27	-10000	0	27
EPHB4	0.018	0.004	-10000	0	-10000	0	0
RAC1	0.018	0.006	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.022	0.01	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	0.023	0.063	-10000	0	-0.39	5	5
BLK	-0.031	0.19	-10000	0	-0.76	16	16
HCK	-0.033	0.19	-10000	0	-0.76	16	16
regulation of stress fiber formation	-0.067	0.069	-10000	0	-0.3	9	9
MAPK8	-0.01	0.14	0.42	2	-0.48	15	17
Ephrin B1/EPHB1-2/RGS3	0.069	0.071	0.31	9	-10000	0	9
endothelial cell migration	-0.016	0.13	0.38	1	-0.51	14	15
NCK2	0.019	0.002	-10000	0	-10000	0	0
PTPN13	-0.014	0.14	-10000	0	-0.66	12	12
regulation of focal adhesion formation	-0.067	0.069	-10000	0	-0.3	9	9
chemotaxis	-0.067	0.069	-10000	0	-0.3	9	9
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
Rac1/GTP	0.056	0.059	0.29	5	-10000	0	5
angiogenesis	-0.032	0.15	-10000	0	-0.6	16	16
LCK	-0.029	0.19	-10000	0	-0.76	16	16

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	-0.015	0.023	-10000	0	-0.35	1	1
SNTA1	0.016	0.036	-10000	0	-0.55	1	1
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	-0.012	0.031	0.22	1	-0.35	1	2
MAPK12	-0.017	0.049	-10000	0	-0.31	7	7
CCND1	-0.009	0.058	-10000	0	-0.36	6	6
p38 gamma/SNTA1	-0.01	0.062	0.18	7	-0.3	7	14
MAP2K3	0.017	0.007	-10000	0	-10000	0	0
PKN1	0.018	0.004	-10000	0	-10000	0	0
G2/M transition checkpoint	-0.017	0.049	-10000	0	-0.31	7	7
MAP2K6	-0.015	0.057	-10000	0	-0.33	8	8
MAPT	-0.11	0.17	0.19	3	-0.32	95	98
MAPK13	-0.013	0.027	0.14	1	-0.41	1	2
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.003	0.001	-10000	0	-10000	0	0

×

Insulin 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
CBL/APS/CAP	-0.071	0.14	-10000	0	-0.29	72	72
TC10/GTP	-0.069	0.14	-10000	0	-0.29	71	71
Insulin Receptor/Insulin/IRS1/Shp2	0.041	0.023	-10000	0	-10000	0	0
HRAS	0.019	0.004	-10000	0	-10000	0	0
APS homodimer	0.019	0.015	0.25	1	-10000	0	1
GRB14	-0.15	0.26	-10000	0	-0.55	75	75
FOXO3	-0.013	0.088	-10000	0	-0.61	5	5
AKT1	-0.084	0.12	0.35	1	-0.28	55	56
INSR	0.02	0.007	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.037	0.029	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.018	0.005	-10000	0	-10000	0	0
SORBS1	-0.17	0.26	-10000	0	-0.55	83	83
CRK	0.018	0.005	-10000	0	-10000	0	0
PTPN1	-0.003	0.041	0.3	1	-10000	0	1
CAV1	-0.006	0.051	0.24	3	-0.31	1	4
CBL/APS/CAP/Crk-II/C3G	-0.064	0.16	-10000	0	-0.31	71	71
Insulin Receptor/Insulin/IRS1/NCK2	0.042	0.022	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.031	0.023	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.013	0.032	-10000	0	-10000	0	0
RPS6KB1	-0.081	0.12	0.33	1	-10000	0	1
PARD6A	0.016	0.036	-10000	0	-0.55	1	1
CBL	0.018	0.005	-10000	0	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0	0.089	-10000	0	-0.57	6	6
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.088	0.1	-10000	0	-10000	0	0
HRAS/GTP	-0.023	0.017	-10000	0	-10000	0	0
Insulin Receptor	0.02	0.007	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.044	0.029	-10000	0	-10000	0	0
PRKCI	-0.017	0.07	-10000	0	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.096	0.12	-10000	0	-0.29	64	64
SHC1	0.018	0.004	-10000	0	-10000	0	0
negative regulation of MAPKKK cascade	0.02	0.082	-10000	0	-0.5	6	6
PI3K	0.038	0.027	-10000	0	-10000	0	0
NCK2	0.019	0.002	-10000	0	-10000	0	0
RHOQ	0.019	0.003	-10000	0	-10000	0	0
mol:H2O2	-0.001	0.004	-10000	0	-10000	0	0
HRAS/GDP	0.014	0.003	-10000	0	-10000	0	0
AKT2	-0.081	0.12	0.35	1	-0.28	49	50
PRKCZ	-0.079	0.19	-10000	0	-0.55	29	29
SH2B2	0.019	0.015	0.25	1	-10000	0	1
SHC/SHIP	-0.005	0.046	-10000	0	-10000	0	0
F2RL2	0.057	0.096	0.25	43	-0.55	1	44
TRIP10	0.019	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insulin/Shc	0.032	0.015	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.025	0.006	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.047	0.026	-10000	0	-10000	0	0
RAPGEF1	0.019	0.004	-10000	0	-10000	0	0
RASA1	0.019	0.002	-10000	0	-10000	0	0
NCK1	0.019	0.002	-10000	0	-10000	0	0
CBL/APS/CAP/Crk-II	-0.072	0.16	-10000	0	-0.32	73	73
TC10/GDP	0.014	0.002	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.04	0.021	-10000	0	-10000	0	0
INPP5D	-0.002	0.049	0.33	1	-10000	0	1
SOS1	0.019	0.004	-10000	0	-10000	0	0
SGK1	-0.009	0.085	-10000	0	-0.67	4	4
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.018	0.004	-10000	0	-10000	0	0
IRS1	0.019	0.016	0.25	1	-10000	0	1
p62DOK/RasGAP	0.02	0.083	-10000	0	-0.5	6	6
INS	-0.012	0.017	-10000	0	-10000	0	0
mol:PI-3-4-P2	-0.002	0.049	0.33	1	-10000	0	1
GRB2	0.019	0.003	-10000	0	-10000	0	0
EIF4EBP1	-0.079	0.11	0.33	1	-10000	0	1
PTPRA	0.02	0.007	-10000	0	-10000	0	0
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
TC10/GTP/CIP4	0.025	0.006	-10000	0	-10000	0	0
PDPK1	0.019	0.002	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.009	0.022	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.032	0.018	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS3	0.025	0.014	-10000	0	-10000	0	0
Par3/Par6	0.058	0.062	-10000	0	-0.31	2	2

×

Visual signal transduction: Rods

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
mol:K +	0.019	0.003	-10000	0	-10000	0	0
GNAT1/GTP	0.011	0.002	-10000	0	-10000	0	0
Metarhodopsin II/Arrestin	0.02	0.012	-10000	0	-10000	0	0
PDE6G/GNAT1/GTP	0.017	0.046	-10000	0	-0.35	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	-0.016	0.003	-10000	0	-10000	0	0
GRK1	-0.002	0.032	0.25	3	-10000	0	3
CNG Channel	0.02	0.072	-10000	0	-0.33	7	7
mol:Na +	0.008	0.058	-10000	0	-0.3	3	3
mol:ADP	-0.002	0.032	0.25	3	-10000	0	3
RGS9-1/Gbeta5/R9AP	-0.058	0.17	-10000	0	-0.37	56	56
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	0.037	0.057	-10000	0	-0.3	3	3
CNGB1	0.003	0.028	0.25	2	-10000	0	2
RDH5	-0.02	0.14	-10000	0	-0.55	17	17
SAG	-0.005	0.027	0.25	2	-10000	0	2
mol:Ca2+	0.006	0.11	0.36	16	-0.29	3	19
Na + (4 Units)	-0.021	0.047	-10000	0	-0.29	3	3
RGS9	-0.061	0.2	-10000	0	-0.55	36	36
GNB1/GNGT1	0.023	0.014	-10000	0	-10000	0	0
GNAT1/GDP	-0.045	0.15	-10000	0	-0.32	56	56
GUCY2D	0.017	0.055	0.25	12	-10000	0	12
GNGT1	-0.008	0.021	0.25	1	-10000	0	1
GUCY2F	-0.016	0.003	-10000	0	-10000	0	0
GNB5	0.019	0.004	-10000	0	-10000	0	0
mol:GMP (4 units)	-0.016	0.063	0.27	1	-0.35	5	6
mol:11-cis-retinal	-0.02	0.14	-10000	0	-0.55	17	17
mol:cGMP	0.039	0.047	0.26	5	-10000	0	5
GNB1	0.018	0.006	-10000	0	-10000	0	0
Rhodopsin	-0.004	0.11	-10000	0	-0.41	17	17
SLC24A1	0.019	0.003	-10000	0	-10000	0	0
CNGA1	0.006	0.073	0.25	1	-0.55	4	5
Metarhodopsin II	0.02	0.017	0.16	3	-10000	0	3
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.051	0.053	0.32	4	-10000	0	4
RGS9BP	-0.048	0.18	-10000	0	-0.55	29	29
Metarhodopsin II/Transducin	0.003	0.021	-10000	0	-10000	0	0
GCAP Family/Ca ++	0.038	0.033	-10000	0	-10000	0	0
PDE6A/B	0.034	0.063	-10000	0	-0.38	3	3
mol:Pi	-0.058	0.17	-10000	0	-0.37	56	56
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	0.028	0.016	-10000	0	-10000	0	0
PDE6B	0.012	0.061	-10000	0	-0.55	3	3
PDE6A	0.034	0.067	0.25	21	-10000	0	21
PDE6G	0.01	0.071	-10000	0	-0.55	4	4
RHO	-0.016	0.002	-10000	0	-10000	0	0
PDE6	-0.038	0.16	-10000	0	-0.31	58	58
GUCA1A	0.014	0.056	0.25	12	-10000	0	12
GC2/GCAP Family	0.046	0.035	-10000	0	-10000	0	0
GUCA1C	-0.014	0.018	0.25	1	-10000	0	1
GUCA1B	0.018	0.006	-10000	0	-10000	0	0

×

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

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
MAP4K1	-0.001	0.11	0.31	4	-0.39	12	16
CRKL	-0.021	0.1	0.24	1	-0.4	14	15
HRAS	-0.001	0.095	0.35	1	-0.35	8	9
mol:PIP3	-0.003	0.11	-10000	0	-0.36	14	14
SPRED1	0.019	0.003	-10000	0	-10000	0	0
SPRED2	0.021	0.021	0.25	2	-10000	0	2
GAB1	-0.021	0.1	-10000	0	-0.41	15	15
FOXO3	-0.007	0.12	0.3	1	-0.37	11	12
AKT1	-0.008	0.12	-10000	0	-0.38	15	15
BAD	-0.009	0.11	0.3	1	-0.37	11	12
megakaryocyte differentiation	-0.022	0.1	-10000	0	-0.39	15	15
GSK3B	-0.01	0.11	-10000	0	-0.37	12	12
RAF1	0.004	0.087	0.28	2	-10000	0	2
SHC1	0.018	0.004	-10000	0	-10000	0	0
STAT3	-0.021	0.1	-10000	0	-0.41	15	15
STAT1	-0.044	0.24	-10000	0	-0.96	15	15
HRAS/SPRED1	0.008	0.086	0.32	1	-10000	0	1
cell proliferation	-0.021	0.1	-10000	0	-0.4	14	14
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
TEC	0.012	0.061	-10000	0	-0.55	3	3
RPS6KB1	-0.007	0.11	-10000	0	-0.4	15	15
HRAS/SPRED2	0.009	0.088	0.3	2	-10000	0	2
LYN/TEC/p62DOK	0.01	0.11	-10000	0	-0.42	12	12
MAPK3	0.007	0.092	0.35	5	-0.27	1	6
STAP1	-0.052	0.15	-10000	0	-0.48	18	18
GRAP2	0.027	0.044	0.25	9	-10000	0	9
JAK2	-0.036	0.2	-10000	0	-0.81	15	15
STAT1 (dimer)	-0.041	0.23	-10000	0	-0.94	15	15
mol:Gleevec	0	0.005	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	0.02	0.12	0.38	1	-0.4	14	15
actin filament polymerization	-0.018	0.096	-10000	0	-0.39	13	13
LYN	0.018	0.005	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.056	0.18	-10000	0	-0.65	17	17
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
CBL/CRKL/GRB2	0.006	0.11	-10000	0	-0.38	13	13
PI3K	0.009	0.11	-10000	0	-0.39	14	14
PTEN	0.017	0.006	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.033	0.28	-10000	0	-1.2	14	14
MAPK8	-0.021	0.1	-10000	0	-0.41	14	14
STAT3 (dimer)	-0.02	0.1	-10000	0	-0.4	15	15
positive regulation of transcription	0.008	0.082	0.29	7	-0.22	1	8
mol:GDP	0.006	0.1	0.39	1	-0.36	10	11
PIK3C2B	-0.019	0.1	-10000	0	-0.41	13	13
CBL/CRKL	-0.002	0.11	0.28	1	-0.38	14	15
FER	-0.021	0.1	-10000	0	-0.41	15	15
SH2B3	-0.017	0.1	-10000	0	-0.41	15	15
PDPK1	-0.003	0.1	-10000	0	-0.35	10	10
SNAI2	-0.013	0.1	-10000	0	-0.4	13	13
positive regulation of cell proliferation	-0.026	0.18	-10000	0	-0.71	15	15
KITLG	0.013	0.04	-10000	0	-0.56	1	1
cell motility	-0.026	0.18	-10000	0	-0.71	15	15
PTPN6	0.016	0.02	0.26	1	-10000	0	1
EPOR	0.005	0.09	-10000	0	-0.62	1	1
STAT5A (dimer)	-0.016	0.15	-10000	0	-0.58	16	16
SOCS1	0.022	0.026	0.25	3	-10000	0	3
cell migration	0.017	0.1	0.4	15	-10000	0	15
SOS1	0.019	0.004	-10000	0	-10000	0	0
EPO	0.019	0.029	0.26	3	-10000	0	3
VAV1	0.032	0.069	0.25	17	-0.55	1	18
GRB10	-0.019	0.1	-10000	0	-0.41	13	13
PTPN11	0.016	0.011	-10000	0	-10000	0	0
SCF/KIT	-0.017	0.11	-10000	0	-0.43	15	15
GO:0007205	0.001	0.006	-10000	0	-10000	0	0
MAP2K1	0.004	0.086	0.33	4	-10000	0	4
CBL	0.018	0.005	-10000	0	-10000	0	0
KIT	-0.05	0.31	-10000	0	-1.3	15	15
MAP2K2	0.006	0.092	0.32	7	-10000	0	7
SHC/Grb2/SOS1	0.012	0.11	-10000	0	-0.41	11	11
STAT5A	-0.019	0.16	-10000	0	-0.59	16	16
GRB2	0.019	0.003	-10000	0	-10000	0	0
response to radiation	-0.013	0.099	-10000	0	-0.4	13	13
SHC/GRAP2	0.032	0.032	-10000	0	-10000	0	0
PTPRO	-0.023	0.1	-10000	0	-0.4	15	15
SH2B2	-0.019	0.098	-10000	0	-0.4	13	13
DOK1	0.019	0.004	-10000	0	-10000	0	0
MATK	-0.017	0.11	-10000	0	-0.41	15	15
CREBBP	0.018	0.034	-10000	0	-10000	0	0
BCL2	0	0.1	-10000	0	-0.72	1	1

×

JNK signaling in the CD4+ TCR pathway

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
LAT/GRAP2/SLP76/HPK1	0.064	0.084	0.4	11	-10000	0	11
MAP4K1	0.036	0.062	0.25	19	-10000	0	19
MAP3K8	0.018	0.004	-10000	0	-10000	0	0
PRKCB	0.013	0.063	0.25	1	-0.55	3	4
DBNL	0.018	0.005	-10000	0	-10000	0	0
CRKL	0.018	0.005	-10000	0	-10000	0	0
MAP3K1	0.011	0.058	0.23	5	-0.28	1	6
JUN	-0.005	0.17	0.3	1	-0.54	21	22
MAP3K7	0.013	0.053	0.23	5	-10000	0	5
GRAP2	0.027	0.044	0.25	9	-10000	0	9
CRK	0.018	0.005	-10000	0	-10000	0	0
MAP2K4	0.025	0.08	0.25	8	-0.34	2	10
LAT	0.027	0.044	0.25	9	-10000	0	9
LCP2	0.021	0.026	0.25	3	-10000	0	3
MAPK8	-0.016	0.17	0.33	1	-0.56	21	22
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.019	0.063	0.27	5	-0.29	1	6
LAT/GRAP2/SLP76/HPK1/HIP-55	0.067	0.082	0.39	11	-10000	0	11

×

HIF-1-alpha transcription factor network

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
PKM2	0.027	0.25	0.53	6	-0.72	4	10
HDAC7	0.019	0.007	-10000	0	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	0.054	0.26	0.61	4	-0.63	2	6
SMAD4	0.019	0.003	-10000	0	-10000	0	0
ID2	0.051	0.26	0.62	4	-0.73	4	8
AP1	0.004	0.086	-10000	0	-0.39	10	10
ABCG2	0.054	0.26	0.62	4	-0.73	4	8
HIF1A	0.02	0.073	0.26	1	-10000	0	1
TFF3	-0.018	0.34	0.62	4	-0.77	17	21
GATA2	0.015	0.057	0.26	2	-0.57	2	4
AKT1	0.018	0.077	0.26	1	-10000	0	1
response to hypoxia	0.01	0.066	0.19	3	-0.19	1	4
MCL1	0.042	0.26	0.62	4	-0.73	4	8
NDRG1	0.047	0.26	0.62	4	-0.72	5	9
SERPINE1	0.057	0.27	0.67	8	-0.79	4	12
FECH	0.048	0.26	0.62	4	-0.73	4	8
FURIN	0.043	0.26	0.62	4	-0.73	4	8
NCOA2	0.022	0.066	0.26	8	-0.55	2	10
EP300	0.026	0.095	0.31	2	-0.31	1	3
HMOX1	0.05	0.26	0.61	5	-0.73	4	9
BHLHE40	0.051	0.26	0.62	4	-0.73	4	8
BHLHE41	0.047	0.26	0.62	4	-0.75	5	9
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.045	0.11	0.37	1	-10000	0	1
ENG	0.029	0.1	0.34	4	-10000	0	4
JUN	0.017	0.011	-10000	0	-10000	0	0
RORA	0.045	0.26	0.62	4	-0.79	4	8
ABCB1	-0.1	0.29	-10000	0	-0.91	26	26
TFRC	0.051	0.26	0.62	4	-0.73	4	8
CXCR4	0.063	0.27	0.6	7	-0.73	4	11
TF	0.07	0.28	0.64	9	-0.71	4	13
CITED2	0.042	0.26	0.6	3	-0.73	4	7
HIF1A/ARNT	0.064	0.31	0.71	9	-0.79	4	13
LDHA	-0.018	0.1	-10000	0	-0.61	4	4
ETS1	0.048	0.26	0.61	3	-0.73	4	7
PGK1	0.045	0.26	0.62	4	-0.73	4	8
NOS2	0.051	0.27	0.62	4	-0.73	5	9
ITGB2	0.047	0.26	0.62	5	-0.73	4	9
ALDOA	0.054	0.26	0.62	4	-0.73	4	8
Cbp/p300/CITED2	0.029	0.27	0.63	2	-0.73	3	5
FOS	-0.006	0.11	-10000	0	-0.55	10	10
HK2	0.076	0.28	0.68	10	-0.73	4	14
SP1	0.006	0.048	-10000	0	-0.21	1	1
GCK	-0.08	0.28	-10000	0	-1.3	8	8
HK1	0.047	0.26	0.62	4	-0.73	4	8
NPM1	0.046	0.26	0.62	4	-0.73	4	8
EGLN1	0.05	0.26	0.62	4	-0.73	4	8
CREB1	0.021	0.008	-10000	0	-10000	0	0
PGM1	0.047	0.26	0.61	3	-0.73	4	7
SMAD3	0.019	0.004	-10000	0	-10000	0	0
EDN1	-0.015	0.25	-10000	0	-1.1	9	9
IGFBP1	0.048	0.26	0.75	4	-0.73	4	8
VEGFA	0.054	0.23	0.5	5	-10000	0	5
HIF1A/JAB1	0.029	0.055	-10000	0	-10000	0	0
CP	-0.021	0.33	0.6	3	-0.78	18	21
CXCL12	0.041	0.27	0.62	4	-0.73	4	8
COPS5	0.019	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4	0.028	0.007	-10000	0	-10000	0	0
BNIP3	0.042	0.27	0.62	4	-0.75	6	10
EGLN3	0.014	0.3	0.6	3	-0.75	12	15
CA9	0.11	0.3	0.62	15	-0.73	4	19
TERT	0.029	0.24	0.63	2	-0.74	3	5
ENO1	0.05	0.26	0.62	4	-0.72	4	8
PFKL	0.046	0.26	0.62	4	-0.73	4	8
NCOA1	0.019	0.004	-10000	0	-10000	0	0
ADM	0.051	0.27	0.62	4	-0.79	4	8
ARNT	0.018	0.071	0.26	1	-10000	0	1
HNF4A	-0.24	0.28	-10000	0	-0.55	116	116
ADFP	0.027	0.25	0.53	6	-0.72	4	10
SLC2A1	0.063	0.24	0.59	9	-10000	0	9
LEP	0.054	0.27	0.61	10	-0.73	4	14
HIF1A/ARNT/Cbp/p300	0.05	0.26	0.63	4	-0.65	2	6
EPO	0.039	0.21	0.54	2	-0.72	5	7
CREBBP	0.028	0.095	0.29	3	-0.31	1	4
HIF1A/ARNT/Cbp/p300/HDAC7	0.048	0.25	0.6	5	-0.63	1	6
PFKFB3	0.044	0.26	0.62	4	-0.73	4	8
NT5E	0.045	0.27	0.61	3	-0.75	5	8

×

Syndecan-2-mediated signaling events

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
Syndecan-2/Fibronectin	0.048	0.069	0.19	47	-10000	0	47
EPHB2	0.048	0.078	0.25	32	-10000	0	32
Syndecan-2/TACI	0.012	0.006	-10000	0	-10000	0	0
LAMA1	0.016	0.1	0.25	12	-0.55	6	18
Syndecan-2/alpha2 ITGB1	0.042	0.053	0.28	1	-0.3	2	3
HRAS	0.019	0.004	-10000	0	-10000	0	0
Syndecan-2/CASK	-0.004	0.002	-10000	0	-10000	0	0
ITGA5	0.018	0.004	-10000	0	-10000	0	0
BAX	-0.011	0.024	-10000	0	-10000	0	0
EPB41	0.017	0.036	-10000	0	-0.55	1	1
positive regulation of cell-cell adhesion	0.015	0.004	-10000	0	-10000	0	0
LAMA3	0.031	0.089	0.25	20	-0.55	3	23
EZR	0.018	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	0.018	0.004	-10000	0	-10000	0	0
Syndecan-2/MMP2	0.028	0.058	0.19	23	-0.34	1	24
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.029	0.019	-10000	0	-10000	0	0
dendrite morphogenesis	0.038	0.061	0.19	32	-10000	0	32
Syndecan-2/GM-CSF	0.019	0.025	0.18	6	-10000	0	6
determination of left/right symmetry	-0.005	0.002	-10000	0	-10000	0	0
Syndecan-2/PKC delta	0.016	0.005	-10000	0	-10000	0	0
GNB2L1	0.018	0.004	-10000	0	-10000	0	0
MAPK3	-0.002	0.043	0.18	11	-10000	0	11
MAPK1	-0.002	0.043	0.18	11	-10000	0	11
Syndecan-2/RACK1	0.024	0.01	-10000	0	-10000	0	0
NF1	0.019	0.004	-10000	0	-10000	0	0
FGFR/FGF/Syndecan-2	-0.005	0.002	-10000	0	-10000	0	0
ITGA2	0.022	0.026	0.25	3	-10000	0	3
MAPK8	-0.008	0.026	0.23	1	-0.34	1	2
Syndecan-2/alpha2/beta1 Integrin	0.034	0.054	-10000	0	-0.3	3	3
Syndecan-2/Kininogen	-0.065	0.15	-10000	0	-0.34	54	54
ITGB1	0.019	0.004	-10000	0	-10000	0	0
SRC	0.001	0.054	0.26	2	-10000	0	2
Syndecan-2/CASK/Protein 4.1	0.013	0.021	-10000	0	-0.31	1	1
extracellular matrix organization	0.016	0.012	0.18	1	-10000	0	1
actin cytoskeleton reorganization	0.048	0.069	0.19	47	-10000	0	47
Syndecan-2/Caveolin-2/Ras	0.025	0.011	-10000	0	-10000	0	0
Syndecan-2/Laminin alpha3	0.024	0.061	0.31	1	-0.34	3	4
Syndecan-2/RasGAP	0.031	0.014	-10000	0	-10000	0	0
alpha5/beta1 Integrin	0.026	0.009	-10000	0	-10000	0	0
PRKCD	0.019	0.003	-10000	0	-10000	0	0
Syndecan-2 dimer	0.038	0.061	0.19	32	-10000	0	32
GO:0007205	0.001	0	-10000	0	-10000	0	0
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	-0.011	0.033	-10000	0	-10000	0	0
RHOA	0.019	0.004	-10000	0	-10000	0	0
SDCBP	0.018	0.005	-10000	0	-10000	0	0
TNFRSF13B	-0.014	0.006	-10000	0	-10000	0	0
RASA1	0.019	0.002	-10000	0	-10000	0	0
alpha2/beta1 Integrin	0.029	0.019	-10000	0	-10000	0	0
Syndecan-2/Synbindin	0.016	0.006	-10000	0	-10000	0	0
TGFB1	0.019	0.016	0.25	1	-10000	0	1
CASP3	-0.003	0.042	0.18	12	-10000	0	12
FN1	0.063	0.092	0.25	48	-10000	0	48
Syndecan-2/IL8	0.021	0.073	0.18	20	-0.34	6	26
SDC2	-0.005	0.002	-10000	0	-10000	0	0
KNG1	-0.14	0.22	-10000	0	-0.55	58	58
Syndecan-2/Neurofibromin	0.015	0.011	-10000	0	-10000	0	0
TRAPPC4	0.018	0.005	-10000	0	-10000	0	0
CSF2	0.01	0.045	0.25	7	-10000	0	7
Syndecan-2/TGFB1	0.016	0.012	0.18	1	-10000	0	1
Syndecan-2/Syntenin/PI-4-5-P2	0.015	0.004	-10000	0	-10000	0	0
Syndecan-2/Ezrin	0.025	0.01	-10000	0	-10000	0	0
PRKACA	-0.007	0.036	0.18	8	-10000	0	8
angiogenesis	0.021	0.073	0.18	20	-0.34	6	26
MMP2	0.035	0.086	0.25	23	-0.55	2	25
IL8	0.024	0.11	0.25	21	-0.55	6	27
calcineurin-NFAT signaling pathway	0.012	0.006	-10000	0	-10000	0	0

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	-0.013	0.005	-10000	0	-10000	0	0
MAP4K4	-0.013	0.064	-10000	0	-0.28	8	8
BAG4	0.018	0.005	-10000	0	-10000	0	0
PKC zeta/ceramide	-0.053	0.099	-10000	0	-0.28	30	30
NFKBIA	0.018	0.005	-10000	0	-10000	0	0
BIRC3	0.011	0.061	-10000	0	-0.55	3	3
BAX	-0.022	0.066	-10000	0	-0.34	9	9
RIPK1	0.018	0.005	-10000	0	-10000	0	0
AKT1	0.025	0.13	0.7	9	-10000	0	9
BAD	-0.039	0.062	0.19	1	-0.22	12	13
SMPD1	0	0.063	0.19	3	-0.28	6	9
RB1	-0.037	0.058	-10000	0	-0.21	14	14
FADD/Caspase 8	-0.013	0.085	-10000	0	-0.33	11	11
MAP2K4	-0.021	0.085	0.2	3	-0.25	4	7
NSMAF	0.018	0.005	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.036	0.069	0.37	1	-0.25	6	7
EGF	-0.21	0.28	-10000	0	-0.55	101	101
mol:ceramide	-0.039	0.063	-10000	0	-0.22	15	15
MADD	0.019	0.004	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.013	0.005	-10000	0	-10000	0	0
ASAH1	0.019	0.004	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.04	0.057	-10000	0	-0.21	14	14
cell proliferation	-0.023	0.079	0.31	1	-0.3	2	3
BID	-0.028	0.16	-10000	0	-0.71	11	11
MAP3K1	-0.037	0.061	0.2	3	-0.22	10	13
EIF2A	-0.043	0.061	0.35	1	-0.24	6	7
TRADD	0.018	0.005	-10000	0	-10000	0	0
CRADD	0.018	0.004	-10000	0	-10000	0	0
MAPK3	-0.034	0.07	0.28	3	-0.24	4	7
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.033	0.07	0.28	3	-0.24	4	7
Cathepsin D/ceramide	-0.03	0.066	-10000	0	-0.22	14	14
FADD	-0.014	0.066	-10000	0	-0.28	9	9
KSR1	-0.039	0.061	0.19	1	-0.22	12	13
MAPK8	-0.053	0.1	-10000	0	-0.29	20	20
PRKRA	-0.04	0.059	-10000	0	-0.22	12	12
PDGFA	0.018	0.005	-10000	0	-10000	0	0
TRAF2	0.018	0.004	-10000	0	-10000	0	0
IGF1	0.019	0.075	0.25	8	-0.55	3	11
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.039	0.063	-10000	0	-0.22	15	15
CTSD	0.019	0.004	-10000	0	-10000	0	0
regulation of nitric oxide biosynthetic process	0.028	0.005	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.023	0.084	0.33	1	-0.32	2	3
PRKCD	0.019	0.003	-10000	0	-10000	0	0
PRKCZ	-0.022	0.15	0.25	1	-0.55	18	19
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.013	0.005	-10000	0	-10000	0	0
RelA/NF kappa B1	0.028	0.005	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.007	0.079	-10000	0	-0.55	5	5
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.01	0.073	-10000	0	-0.29	10	10
TNFR1A/BAG4/TNF-alpha	0.038	0.03	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	-0.013	0.005	-10000	0	-10000	0	0
MAP2K1	-0.033	0.071	0.32	3	-0.24	4	7
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.019	0.003	-10000	0	-10000	0	0
CYCS	-0.026	0.047	-10000	0	-0.19	7	7
TNFRSF1A	0.018	0.005	-10000	0	-10000	0	0
NFKB1	0.019	0.001	-10000	0	-10000	0	0
TNFR1A/BAG4	0.026	0.009	-10000	0	-10000	0	0
EIF2AK2	-0.042	0.059	0.19	2	-0.25	6	8
TNF-alpha/TNFR1A/FAN	0.039	0.031	-10000	0	-10000	0	0
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.003	0.077	-10000	0	-0.38	7	7
MAP2K2	-0.036	0.069	0.34	1	-0.24	6	7
SMPD3	-0.01	0.099	0.18	3	-0.36	15	18
TNF	0.025	0.045	0.25	9	-10000	0	9
PKC zeta/PAR4	-0.016	0.12	0.19	1	-0.32	30	31
mol:PHOSPHOCHOLINE	0.086	0.12	0.23	95	-0.17	1	96
NF kappa B1/RelA/I kappa B alpha	0.013	0.1	-10000	0	-0.32	18	18
AIFM1	-0.031	0.055	-10000	0	-0.19	16	16
BCL2	0.018	0.004	-10000	0	-10000	0	0

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	0.049	0.18	0.43	7	-0.64	8	15
oxygen homeostasis	0.012	0.016	-10000	0	-10000	0	0
TCEB2	0.019	0.003	-10000	0	-10000	0	0
TCEB1	0.018	0.005	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	0.041	0.12	0.35	5	-10000	0	5
EPO	0.086	0.16	0.54	9	-10000	0	9
FIH (dimer)	0.031	0.018	-10000	0	-10000	0	0
APEX1	0.031	0.02	-10000	0	-10000	0	0
SERPINE1	0.1	0.19	0.55	20	-0.58	1	21
FLT1	-0.05	0.19	-10000	0	-0.61	18	18
ADORA2A	0.093	0.17	0.49	18	-10000	0	18
germ cell development	0.094	0.17	0.53	13	-0.62	1	14
SLC11A2	0.094	0.17	0.54	13	-10000	0	13
BHLHE40	0.092	0.17	0.53	14	-10000	0	14
HIF1AN	0.031	0.018	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	0.073	0.14	0.42	12	-10000	0	12
ETS1	0.021	0.006	-10000	0	-10000	0	0
CITED2	0.006	0.082	-10000	0	-0.65	3	3
KDR	-0.007	0.12	-10000	0	-0.67	4	4
PGK1	0.096	0.17	0.53	14	-10000	0	14
SIRT1	0.018	0.005	-10000	0	-10000	0	0
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	0.13	0.2	0.64	12	-10000	0	12
EPAS1	0.037	0.11	0.35	11	-0.31	1	12
SP1	0.04	0.045	-10000	0	-10000	0	0
ABCG2	0.096	0.17	0.54	13	-10000	0	13
EFNA1	0.094	0.17	0.54	12	-10000	0	12
FXN	0.096	0.17	0.49	18	-10000	0	18
POU5F1	0.095	0.17	0.54	13	-0.65	1	14
neuron apoptosis	-0.12	0.19	-10000	0	-0.62	13	13
EP300	0.019	0.004	-10000	0	-10000	0	0
EGLN3	-0.033	0.18	-10000	0	-0.54	28	28
EGLN2	0.029	0.018	-10000	0	-10000	0	0
EGLN1	0.031	0.018	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.034	0.014	-10000	0	-10000	0	0
VHL	0.018	0.004	-10000	0	-10000	0	0
ARNT	0.031	0.022	-10000	0	-10000	0	0
SLC2A1	0.1	0.18	0.53	22	-10000	0	22
TWIST1	0.11	0.19	0.49	31	-0.6	1	32
ELK1	0.022	0.017	0.26	1	-10000	0	1
HIF2A/ARNT/Cbp/p300	0.073	0.14	0.43	11	-10000	0	11
VEGFA	0.095	0.17	0.54	13	-10000	0	13
CREBBP	0.019	0.003	-10000	0	-10000	0	0

×

S1P3 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
PDGFRB	0.02	0.015	0.25	1	-10000	0	1
mol:S1P	0	0.002	-10000	0	-10000	0	0
S1P1/S1P/Gi	-0.052	0.12	-10000	0	-0.28	44	44
GNAO1	-0.05	0.19	0.26	1	-0.55	31	32
S1P/S1P3/G12/G13	0.031	0.026	-10000	0	-0.32	1	1
AKT1	-0.012	0.087	-10000	0	-0.44	7	7
AKT3	-0.04	0.14	-10000	0	-0.87	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.02	0.015	0.25	1	-10000	0	1
GNAI2	0.019	0.005	-10000	0	-10000	0	0
GNAI3	0.019	0.005	-10000	0	-10000	0	0
GNAI1	0.009	0.071	-10000	0	-0.55	4	4
mol:GDP	0	0	-10000	0	-10000	0	0
S1PR3	0.017	0.036	-10000	0	-0.55	1	1
S1PR2	0.018	0.005	-10000	0	-10000	0	0
EDG1	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.043	0.13	-10000	0	-0.32	34	34
MAPK3	-0.045	0.12	-10000	0	-0.47	9	9
MAPK1	-0.046	0.12	-10000	0	-0.47	9	9
JAK2	-0.049	0.13	-10000	0	-0.46	11	11
CXCR4	-0.042	0.12	-10000	0	-0.32	30	30
FLT1	0.018	0.008	-10000	0	-10000	0	0
RhoA/GDP	0.014	0.003	-10000	0	-10000	0	0
Rac1/GDP	0.013	0.004	-10000	0	-10000	0	0
SRC	-0.048	0.12	-10000	0	-0.31	34	34
S1P/S1P3/Gi	-0.043	0.13	-10000	0	-0.32	34	34
RAC1	0.018	0.006	-10000	0	-10000	0	0
RhoA/GTP	-0.039	0.13	-10000	0	-0.45	9	9
VEGFA	0.018	0.007	-10000	0	-10000	0	0
S1P/S1P2/Gi	-0.041	0.12	-10000	0	-0.28	41	41
VEGFR1 homodimer/VEGFA homodimer	0.026	0.013	-10000	0	-10000	0	0
RHOA	0.019	0.004	-10000	0	-10000	0	0
S1P/S1P3/Gq	-0.006	0.08	-10000	0	-0.29	16	16
GNAQ	0.019	0.003	-10000	0	-10000	0	0
GNAZ	-0.017	0.14	-10000	0	-0.55	16	16
G12/G13	0.026	0.009	-10000	0	-10000	0	0
GNA14	-0.017	0.14	-10000	0	-0.55	16	16
GNA15	0.024	0.033	0.25	5	-10000	0	5
GNA12	0.018	0.005	-10000	0	-10000	0	0
GNA13	0.019	0.004	-10000	0	-10000	0	0
GNA11	0.017	0.036	-10000	0	-0.55	1	1
Rac1/GTP	-0.04	0.12	-10000	0	-0.46	9	9

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	-0.007	0.027	-10000	0	-10000	0	0
HSPA8	0.018	0.012	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	0.02	0.091	0.39	1	-0.37	6	7
AKT1	0.023	0.016	-10000	0	-10000	0	0
GSC	0.15	0.17	0.44	2	-10000	0	2
NKX2-5	0.001	0	-10000	0	-10000	0	0
muscle cell differentiation	-0.058	0.058	-10000	0	-0.28	1	1
SMAD2-3/SMAD4/SP1	0.097	0.074	0.29	1	-10000	0	1
SMAD4	0.032	0.034	-10000	0	-10000	0	0
CBFB	0.018	0.005	-10000	0	-10000	0	0
SAP18	0.018	0.006	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.019	0.066	-10000	0	-10000	0	0
SMAD3/SMAD4/VDR	0.001	0.098	-10000	0	-0.31	17	17
MYC	0.004	0.047	-10000	0	-0.55	1	1
CDKN2B	-0.002	0.21	0.45	3	-0.72	5	8
AP1	0.014	0.07	-10000	0	-0.29	7	7
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.029	0.059	-10000	0	-0.37	1	1
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.038	0.064	0.33	3	-0.35	1	4
SP3	0.02	0.002	-10000	0	-10000	0	0
CREB1	0.019	0.003	-10000	0	-10000	0	0
FOXH1	0.04	0.035	0.27	4	-10000	0	4
SMAD3/SMAD4/GR	0.032	0.053	-10000	0	-10000	0	0
GATA3	-0.028	0.16	-10000	0	-0.55	21	21
SKI/SIN3/HDAC complex/NCoR1	0.006	0.048	-10000	0	-0.31	3	3
MEF2C/TIF2	0.059	0.067	0.32	2	-0.3	1	3
endothelial cell migration	-0.018	0.14	0.75	4	-0.38	1	5
MAX	0.01	0.025	-10000	0	-10000	0	0
RBBP7	0.019	0.005	-10000	0	-10000	0	0
RBBP4	0.02	0.004	-10000	0	-10000	0	0
RUNX2	0.099	0.11	0.25	88	-10000	0	88
RUNX3	0.064	0.093	0.25	49	-10000	0	49
RUNX1	0.053	0.083	0.25	37	-10000	0	37
CTBP1	0.019	0.004	-10000	0	-10000	0	0
NR3C1	0.01	0.025	-10000	0	-10000	0	0
VDR	-0.022	0.14	-10000	0	-0.55	18	18
CDKN1A	0.013	0.095	-10000	0	-0.58	3	3
KAT2B	-0.003	0.021	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	0.11	0.079	0.3	3	-10000	0	3
DCP1A	0.019	0.003	-10000	0	-10000	0	0
SKI	0.018	0.006	-10000	0	-10000	0	0
SERPINE1	0.018	0.15	0.38	1	-0.76	4	5
SMAD3/SMAD4/ATF2	0.042	0.043	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	0.031	0.077	-10000	0	-0.39	6	6
SAP30	0.019	0.004	-10000	0	-10000	0	0
Cbp/p300/PIAS3	-0.005	0.045	-10000	0	-10000	0	0
JUN	0.007	0.07	-10000	0	-0.3	1	1
SMAD3/SMAD4/IRF7	0.042	0.046	-10000	0	-10000	0	0
TFE3	0.022	0.012	-10000	0	-10000	0	0
COL1A2	0.065	0.15	0.31	1	-0.74	3	4
mesenchymal cell differentiation	-0.087	0.085	-10000	0	-0.27	8	8
DLX1	0.096	0.11	0.25	85	-10000	0	85
TCF3	0.019	0.015	0.25	1	-10000	0	1
FOS	0.001	0.11	-10000	0	-0.55	10	10
SMAD3/SMAD4/Max	0.033	0.053	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.004	0.036	-10000	0	-10000	0	0
ZBTB17	0.01	0.024	-10000	0	-10000	0	0
LAMC1	0.022	0.051	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.041	0.043	-10000	0	-10000	0	0
IRF7	0.021	0.021	0.25	2	-10000	0	2
ESR1	0.002	0.11	0.26	17	-0.55	6	23
HNF4A	-0.26	0.27	-10000	0	-0.55	116	116
MEF2C	0.052	0.066	0.31	3	-10000	0	3
SMAD2-3/SMAD4	0.07	0.053	-10000	0	-10000	0	0
Cbp/p300/Src-1	-0.002	0.039	-10000	0	-10000	0	0
IGHV3OR16-13	0.003	0.052	-10000	0	-0.35	5	5
TGIF2/HDAC complex	0.019	0.004	-10000	0	-10000	0	0
CREBBP	-0.005	0.024	-10000	0	-10000	0	0
SKIL	0.02	0.015	0.25	1	-10000	0	1
HDAC1	0.019	0.004	-10000	0	-10000	0	0
HDAC2	0.019	0.005	-10000	0	-10000	0	0
SNIP1	0.018	0.011	-10000	0	-10000	0	0
GCN5L2	-0.006	0.009	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.052	0.044	-10000	0	-10000	0	0
MSG1/HSC70	0.047	0.056	0.2	29	-10000	0	29
SMAD2	0.043	0.022	-10000	0	-10000	0	0
SMAD3	0.012	0.035	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.016	0.047	-10000	0	-0.25	3	3
SMAD2/SMAD2/SMAD4	0.01	0.043	0.2	2	-10000	0	2
NCOR1	0.017	0.007	-10000	0	-10000	0	0
NCOA2	0.021	0.066	0.25	8	-0.55	2	10
NCOA1	0.019	0.004	-10000	0	-10000	0	0
MYOD/E2A	0.05	0.059	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.1	0.078	0.33	1	-10000	0	1
IFNB1	0.005	0.037	-10000	0	-10000	0	0
SMAD3/SMAD4/MEF2C	0.074	0.065	-10000	0	-10000	0	0
CITED1	0.048	0.077	0.26	31	-10000	0	31
SMAD2-3/SMAD4/ARC105	0.073	0.054	-10000	0	-10000	0	0
RBL1	0.029	0.048	0.25	11	-10000	0	11
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.034	0.077	0.34	6	-0.58	1	7
RUNX1-3/PEBPB2	0.082	0.077	0.33	4	-10000	0	4
SMAD7	0.034	0.076	0.34	1	-10000	0	1
MYC/MIZ-1	0.009	0.049	-10000	0	-0.41	1	1
SMAD3/SMAD4	-0.049	0.11	0.27	2	-0.36	6	8
IL10	-0.013	0.12	0.29	6	-0.36	20	26
PIASy/HDAC complex	0.022	0.017	-10000	0	-10000	0	0
PIAS3	-0.003	0.02	-10000	0	-10000	0	0
CDK2	-0.004	0.023	-10000	0	-10000	0	0
IL5	-0.019	0.1	0.25	1	-0.34	19	20
CDK4	-0.001	0.021	-10000	0	-10000	0	0
PIAS4	0.022	0.017	-10000	0	-10000	0	0
ATF3	0.005	0.086	-10000	0	-0.55	6	6
SMAD3/SMAD4/SP1	0.065	0.063	-10000	0	-10000	0	0
FOXG1	0.074	0.11	0.25	71	-10000	0	71
FOXO3	-0.006	0.022	-10000	0	-10000	0	0
FOXO1	-0.006	0.022	-10000	0	-10000	0	0
FOXO4	-0.006	0.022	-10000	0	-10000	0	0
heart looping	0.052	0.066	0.31	3	-10000	0	3
CEBPB	0.021	0.01	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	0.09	0.079	0.26	3	-10000	0	3
MYOD1	0.039	0.094	0.25	40	-10000	0	40
SMAD3/SMAD4/HNF4	-0.14	0.2	-10000	0	-0.36	112	112
SMAD3/SMAD4/GATA3	0.01	0.12	-10000	0	-0.37	21	21
SnoN/SIN3/HDAC complex/NCoR1	0.02	0.015	0.25	1	-10000	0	1
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.095	0.086	0.32	6	-10000	0	6
SMAD3/SMAD4/SP1-3	0.073	0.062	-10000	0	-10000	0	0
MED15	0.018	0.005	-10000	0	-10000	0	0
SP1	0.032	0.026	-10000	0	-10000	0	0
SIN3B	0.019	0.004	-10000	0	-10000	0	0
SIN3A	0.019	0.004	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.11	0.074	0.3	2	-10000	0	2
ITGB5	0.025	0.056	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0	0.041	-10000	0	-0.28	2	2
SMAD3/SMAD4/AR	0.035	0.098	0.26	1	-0.37	9	10
AR	0.013	0.13	0.25	20	-0.55	10	30
negative regulation of cell growth	0.011	0.052	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	0.061	0.068	0.27	3	-10000	0	3
E2F5	0.011	0.061	-10000	0	-0.55	3	3
E2F4	0.018	0.005	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.1	0.066	0.29	2	-10000	0	2
SMAD2-3/SMAD4/FOXO1-3a-4	0.03	0.06	0.34	3	-0.39	1	4
TFDP1	0.017	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.041	0.088	0.43	2	-0.3	6	8
SMAD3/SMAD4/RUNX2	0.087	0.085	0.27	8	-10000	0	8
TGIF2	0.019	0.004	-10000	0	-10000	0	0
TGIF1	0.018	0.004	-10000	0	-10000	0	0
ATF2	0.019	0.002	-10000	0	-10000	0	0

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.019	0.004	-10000	0	-10000	0	0
SPHK1	0.078	0.1	0.25	64	-10000	0	64
GNAI2	0.019	0.003	-10000	0	-10000	0	0
mol:S1P	0.03	0.045	0.22	2	-10000	0	2
GNAO1	-0.05	0.19	0.25	1	-0.55	31	32
mol:Sphinganine-1-P	0.025	0.068	-10000	0	-10000	0	0
growth factor activity	0	0	-10000	0	-10000	0	0
S1P/S1P2/G12/G13	0.045	0.044	-10000	0	-10000	0	0
GNAI3	0.019	0.003	-10000	0	-10000	0	0
G12/G13	0.026	0.009	-10000	0	-10000	0	0
S1PR3	0.017	0.036	-10000	0	-0.55	1	1
S1PR2	0.018	0.005	-10000	0	-10000	0	0
EDG1	0	0	-10000	0	-10000	0	0
S1P1/S1P	0.015	0.04	-10000	0	-0.22	1	1
S1PR5	0.029	0.05	0.25	12	-10000	0	12
S1PR4	0.024	0.033	0.25	5	-10000	0	5
GNAI1	0.009	0.071	-10000	0	-0.55	4	4
S1P/S1P5/G12	0.043	0.053	0.24	4	-10000	0	4
S1P/S1P3/Gq	0.004	0.089	-10000	0	-0.32	11	11
S1P/S1P4/Gi	-0.029	0.12	-10000	0	-0.32	23	23
GNAQ	0.019	0.003	-10000	0	-10000	0	0
GNAZ	-0.017	0.14	-10000	0	-0.55	16	16
GNA14	-0.017	0.14	-10000	0	-0.55	16	16
GNA15	0.024	0.033	0.25	5	-10000	0	5
GNA12	0.018	0.005	-10000	0	-10000	0	0
GNA13	0.019	0.004	-10000	0	-10000	0	0
GNA11	0.017	0.036	-10000	0	-0.55	1	1
ABCC1	0.019	0.004	-10000	0	-10000	0	0

×

Presenilin action in Notch and Wnt signaling

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
Delta 1/NOTCH/NOTCH(cleaved)	0.019	0.072	-10000	0	-0.4	7	7
HDAC1	0.018	0.006	-10000	0	-10000	0	0
AES	0.019	0.004	-10000	0	-10000	0	0
FBXW11	0.019	0.004	-10000	0	-10000	0	0
DTX1	-0.024	0.16	0.25	2	-0.55	20	22
LRP6/FZD1	0.03	0.029	-10000	0	-10000	0	0
TLE1	0.022	0.029	0.25	4	-10000	0	4
AP1	-0.032	0.11	-10000	0	-0.3	31	31
NCSTN	0.018	0.005	-10000	0	-10000	0	0
ADAM10	0.019	0.004	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.006	0.077	-10000	0	-0.49	3	3
NICD/RBPSUH	0.017	0.071	-10000	0	-0.39	7	7
WIF1	0.036	0.087	0.25	34	-10000	0	34
NOTCH1	0.002	0.07	-10000	0	-0.41	7	7
PSENEN	0.018	0.005	-10000	0	-10000	0	0
KREMEN2	0.048	0.078	0.25	32	-10000	0	32
DKK1	0.03	0.17	0.25	50	-0.55	15	65
beta catenin/beta TrCP1	0.032	0.085	0.27	1	-0.39	1	2
APH1B	0.019	0.004	-10000	0	-10000	0	0
APH1A	0.018	0.005	-10000	0	-10000	0	0
AXIN1	0.004	0.062	-10000	0	-0.46	2	2
CtBP/CBP/TCF1/TLE1/AES	-0.006	0.062	-10000	0	-10000	0	0
PSEN1	0.018	0.005	-10000	0	-10000	0	0
FOS	-0.004	0.11	-10000	0	-0.55	10	10
JUN	0.018	0.006	-10000	0	-10000	0	0
MAP3K7	0.018	0.005	-10000	0	-10000	0	0
CTNNB1	0.026	0.089	0.28	2	-0.4	1	3
MAPK3	0.019	0.004	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.065	0.08	0.33	7	-0.32	2	9
HNF1A	-0.011	0.12	-10000	0	-0.55	13	13
CTBP1	0.018	0.005	-10000	0	-10000	0	0
MYC	0	0.13	-10000	0	-0.89	5	5
NKD1	-0.033	0.17	0.25	5	-0.55	24	29
FZD1	0.025	0.039	0.25	7	-10000	0	7
NOTCH1 precursor/Deltex homolog 1	-0.004	0.11	-10000	0	-0.43	7	7
apoptosis	-0.033	0.11	-10000	0	-0.3	32	32
Delta 1/NOTCHprecursor	0.016	0.072	-10000	0	-0.4	7	7
DLL1	0.019	0.015	0.25	1	-10000	0	1
PPARD	-0.013	0.16	-10000	0	-0.81	10	10
Gamma Secretase	0.044	0.026	-10000	0	-10000	0	0
APC	0.009	0.046	0.24	1	-0.33	1	2
DVL1	0.01	0.012	-10000	0	-10000	0	0
CSNK2A1	0.018	0.005	-10000	0	-10000	0	0
MAP3K7IP1	0	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	0.05	0.12	0.33	3	-0.34	15	18
LRP6	0.018	0.005	-10000	0	-10000	0	0
CSNK1A1	0.019	0.004	-10000	0	-10000	0	0
NLK	0.006	0.004	-10000	0	-10000	0	0
CCND1	-0.001	0.14	-10000	0	-0.9	6	6
WNT1	0.031	0.069	0.25	21	-10000	0	21
Axin1/APC/beta catenin	0.031	0.1	0.32	6	-0.41	3	9
DKK2	0.041	0.091	0.25	29	-0.55	2	31
NOTCH1 precursor/DVL1	-0.006	0.11	-10000	0	-0.66	3	3
GSK3B	0.019	0.002	-10000	0	-10000	0	0
FRAT1	0.018	0.005	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.001	0.11	-10000	0	-0.43	7	7
PPP2R5D	0.034	0.095	0.29	24	-0.48	2	26
MAPK1	0.018	0.005	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.067	0.074	0.34	8	-10000	0	8
RBPJ	0.019	0.004	-10000	0	-10000	0	0
CREBBP	0.02	0.004	-10000	0	-10000	0	0

×

IFN-gamma pathway

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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.063	0.065	0.3	1	-10000	0	1
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	0.018	0.005	-10000	0	-10000	0	0
STAT1 (dimer)/Cbp/p300	0.045	0.091	0.28	17	-10000	0	17
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.041	0.028	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.02	0.053	-10000	0	-0.3	1	1
CaM/Ca2+	0.057	0.058	0.26	1	-10000	0	1
RAP1A	0.019	0.003	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	0.022	0.063	0.2	1	-10000	0	1
AKT1	0.031	0.085	0.26	17	-10000	0	17
MAP2K1	0.034	0.089	0.28	18	-10000	0	18
MAP3K11	0.037	0.088	0.29	15	-10000	0	15
IFNGR1	0.022	0.011	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.035	0.15	-10000	0	-0.4	31	31
Rap1/GTP	-0.012	0.024	-10000	0	-10000	0	0
CRKL/C3G	0.026	0.009	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.067	0.067	0.31	1	-10000	0	1
CEBPB	0.049	0.12	0.35	7	-0.75	1	8
STAT3	0.019	0.001	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.06	0.12	-10000	0	-0.72	4	4
STAT1	0.038	0.089	0.29	15	-10000	0	15
CALM1	0.018	0.004	-10000	0	-10000	0	0
IFN-gamma (dimer)	0.062	0.1	0.25	56	-10000	0	56
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
STAT1 (dimer)/PIAS1	0.039	0.091	0.28	17	-10000	0	17
CEBPB/PTGES2/Cbp/p300	0.009	0.054	-10000	0	-0.44	1	1
mol:Ca2+	0.059	0.062	0.29	1	-10000	0	1
MAPK3	0.032	0.16	0.39	2	-0.76	7	9
STAT1 (dimer)	-0.011	0.075	-10000	0	-0.41	1	1
MAPK1	0.037	0.13	0.39	2	-0.7	5	7
JAK2	0.024	0.019	0.26	1	-10000	0	1
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
JAK1	0.024	0.012	-10000	0	-10000	0	0
CAMK2D	0.019	0.002	-10000	0	-10000	0	0
DAPK1	0.045	0.095	0.32	7	-0.4	1	8
SMAD7	0.009	0.062	0.25	7	-10000	0	7
CBL/CRKL/C3G	0.035	0.089	0.28	16	-10000	0	16
PI3K	0.052	0.051	-10000	0	-10000	0	0
IFNG	0.062	0.1	0.25	56	-10000	0	56
apoptosis	0.044	0.084	0.31	6	-0.32	1	7
CAMK2G	0.018	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	0.019	0.001	-10000	0	-10000	0	0
CAMK2A	-0.044	0.18	-10000	0	-0.55	28	28
CAMK2B	0.033	0.074	0.25	20	-0.55	1	21
FRAP1	0.027	0.08	0.25	17	-10000	0	17
PRKCD	0.033	0.089	0.27	18	-10000	0	18
RAP1B	0.017	0.007	-10000	0	-10000	0	0
negative regulation of cell growth	-0.02	0.053	-10000	0	-0.3	1	1
PTPN2	0.018	0.004	-10000	0	-10000	0	0
EP300	0.019	0.004	-10000	0	-10000	0	0
IRF1	0.03	0.083	0.36	4	-10000	0	4
STAT1 (dimer)/PIASy	0.036	0.089	0.28	15	-10000	0	15
SOCS1	0.001	0.14	-10000	0	-1	4	4
mol:GDP	0.028	0.077	0.24	13	-10000	0	13
CASP1	0.007	0.061	0.25	6	-0.31	1	7
PTGES2	0.019	0.003	-10000	0	-10000	0	0
IRF9	0.025	0.05	0.19	6	-10000	0	6
mol:PI-3-4-5-P3	0.037	0.039	-10000	0	-10000	0	0
RAP1/GDP	-0.002	0.042	-10000	0	-10000	0	0
CBL	0.037	0.087	0.27	18	-10000	0	18
MAP3K1	0.039	0.09	0.29	17	-10000	0	17
PIAS1	0.018	0.004	-10000	0	-10000	0	0
PIAS4	0.018	0.005	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.02	0.053	-10000	0	-0.3	1	1
PTPN11	0.034	0.083	0.26	17	-10000	0	17
CREBBP	0.019	0.003	-10000	0	-10000	0	0
RAPGEF1	0.019	0.004	-10000	0	-10000	0	0

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.02	0.015	0.25	1	-10000	0	1
alphaV beta3 Integrin	0.02	0.06	-10000	0	-0.41	5	5
PTK2	-0.006	0.094	-10000	0	-0.48	6	6
positive regulation of JNK cascade	-0.024	0.11	-10000	0	-0.34	14	14
CDC42/GDP	-0.01	0.14	-10000	0	-0.47	12	12
Rac1/GDP	-0.012	0.13	0.35	1	-0.47	11	12
RAP1B	0.017	0.007	-10000	0	-10000	0	0
RAP1A	0.019	0.003	-10000	0	-10000	0	0
CTNNB1	0.019	0.003	-10000	0	-10000	0	0
CDC42/GTP	-0.024	0.14	-10000	0	-0.43	14	14
nectin-3/I-afadin	0.016	0.07	-10000	0	-0.43	6	6
RAPGEF1	0.001	0.12	0.5	1	-0.48	8	9
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.01	0.12	-10000	0	-0.55	8	8
PDGFB-D/PDGFRB	0.02	0.015	0.25	1	-10000	0	1
TLN1	-0.013	0.029	-10000	0	-0.23	1	1
Rap1/GTP	-0.005	0.078	-10000	0	-0.34	8	8
IQGAP1	0.019	0.004	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.029	0.027	-10000	0	-0.32	1	1
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.016	0.07	-10000	0	-0.43	6	6
PVR	0.018	0.004	-10000	0	-10000	0	0
Necl-5(dimer)	0.018	0.004	-10000	0	-10000	0	0
mol:GDP	-0.023	0.16	0.38	1	-0.58	12	13
MLLT4	0.016	0.036	-10000	0	-0.55	1	1
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
PI3K	0.042	0.063	-10000	0	-0.32	6	6
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.024	0.029	-10000	0	-0.41	1	1
positive regulation of lamellipodium assembly	-0.008	0.094	-10000	0	-0.35	12	12
PVRL1	0.018	0.005	-10000	0	-10000	0	0
PVRL3	0.008	0.079	-10000	0	-0.55	5	5
PVRL2	0.018	0.005	-10000	0	-10000	0	0
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
CDH1	-0.21	0.28	0.25	2	-0.55	101	103
CLDN1	0.007	0.12	0.25	11	-0.55	10	21
JAM-A/CLDN1	0.024	0.098	-10000	0	-0.34	15	15
SRC	-0.012	0.13	-10000	0	-0.61	8	8
ITGB3	0.008	0.079	-10000	0	-0.55	5	5
nectin-1(dimer)/I-afadin/I-afadin	0.024	0.029	-10000	0	-0.41	1	1
FARP2	-0.048	0.2	-10000	0	-0.58	18	18
RAC1	0.018	0.006	-10000	0	-10000	0	0
CTNNA1	0.019	0.003	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.025	0.063	-10000	0	-0.37	6	6
nectin-1/I-afadin	0.024	0.029	-10000	0	-0.41	1	1
nectin-2/I-afadin	0.024	0.028	-10000	0	-0.41	1	1
RAC1/GTP/IQGAP1/filamentous actin	0.023	0.009	-10000	0	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.025	0.063	-10000	0	-0.37	6	6
CDC42/GTP/IQGAP1/filamentous actin	0.024	0.008	-10000	0	-10000	0	0
F11R	0.018	0.005	-10000	0	-10000	0	0
positive regulation of filopodium formation	-0.024	0.11	-10000	0	-0.34	14	14
alphaV/beta3 Integrin/Talin	0.016	0.079	0.26	3	-0.32	5	8
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.024	0.028	-10000	0	-0.41	1	1
nectin-2(dimer)/I-afadin/I-afadin	0.024	0.028	-10000	0	-0.41	1	1
PIP5K1C	-0.01	0.031	-10000	0	-0.21	6	6
VAV2	-0.01	0.16	-10000	0	-0.61	12	12
RAP1/GDP	-0.005	0.12	0.35	1	-0.43	9	10
ITGAV	0.019	0.003	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.025	0.063	-10000	0	-0.37	6	6
nectin-3(dimer)/I-afadin/I-afadin	0.016	0.07	-10000	0	-0.43	6	6
Rac1/GTP	-0.007	0.12	-10000	0	-0.44	11	11
PTPRM	0	0.035	-10000	0	-0.22	6	6
E-cadherin/beta catenin/alpha catenin	-0.089	0.16	-10000	0	-0.3	89	89
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.019	0.004	-10000	0	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	-0.015	0.11	-10000	0	-0.46	9	9
BAG4	0.018	0.005	-10000	0	-10000	0	0
BAD	-0.003	0.055	0.27	3	-0.18	6	9
NFKBIA	0.018	0.005	-10000	0	-10000	0	0
BIRC3	0.011	0.061	-10000	0	-0.55	3	3
BAX	-0.003	0.052	0.2	4	-0.18	6	10
EnzymeConsortium:3.1.4.12	0	0.032	0.087	4	-0.1	12	16
IKBKB	-0.016	0.12	0.3	2	-0.41	13	15
MAP2K2	-0.002	0.067	0.24	9	-0.22	3	12
MAP2K1	0	0.072	0.27	9	-0.22	3	12
SMPD1	-0.002	0.04	0.13	2	-0.15	8	10
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	-0.018	0.12	0.24	1	-0.45	12	13
MAP2K4	0.013	0.072	0.18	26	-0.22	1	27
protein ubiquitination	-0.016	0.12	0.3	1	-0.43	13	14
EnzymeConsortium:2.7.1.37	0.004	0.076	0.29	7	-0.25	2	9
response to UV	0	0.001	0.004	8	-0.002	2	10
RAF1	-0.001	0.064	0.24	8	-0.22	3	11
CRADD	0.019	0.005	-10000	0	-10000	0	0
mol:ceramide	-0.001	0.05	0.15	3	-0.15	13	16
I-kappa-B-alpha/RELA/p50/ubiquitin	0.024	0.007	-10000	0	-10000	0	0
MADD	0.019	0.004	-10000	0	-10000	0	0
MAP3K1	-0.001	0.055	0.18	7	-0.19	5	12
TRADD	0.018	0.005	-10000	0	-10000	0	0
RELA/p50	0.019	0.003	-10000	0	-10000	0	0
MAPK3	-0.001	0.076	0.27	7	-0.26	6	13
MAPK1	-0.001	0.073	0.27	7	-0.24	3	10
p50/RELA/I-kappa-B-alpha	0.027	0.008	-10000	0	-10000	0	0
FADD	-0.018	0.11	-10000	0	-0.44	10	10
KSR1	-0.003	0.052	0.25	2	-0.18	6	8
MAPK8	0.011	0.073	0.23	7	-0.23	2	9
TRAF2	0.018	0.004	-10000	0	-10000	0	0
response to radiation	0	0.001	0.003	5	-10000	0	5
CHUK	-0.013	0.11	0.3	1	-0.45	8	9
TNF R/SODD	0.026	0.009	-10000	0	-10000	0	0
TNF	0.025	0.045	0.25	9	-10000	0	9
CYCS	-0.002	0.058	0.2	6	-0.18	8	14
IKBKG	-0.014	0.12	0.28	2	-0.42	12	14
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.016	0.12	-10000	0	-0.43	13	13
RELA	0.019	0.003	-10000	0	-10000	0	0
RIPK1	0.018	0.005	-10000	0	-10000	0	0
AIFM1	-0.006	0.055	0.2	4	-0.19	6	10
TNF/TNF R/SODD	0.038	0.03	-10000	0	-10000	0	0
TNFRSF1A	0.018	0.005	-10000	0	-10000	0	0
response to heat	0	0.001	0.003	5	-10000	0	5
CASP8	-0.005	0.13	-10000	0	-0.64	9	9
NSMAF	-0.012	0.12	0.25	2	-0.43	11	13
response to hydrogen peroxide	0	0.001	0.004	8	-0.002	2	10
BCL2	0.018	0.004	-10000	0	-10000	0	0

×

FAS signaling pathway (CD95)

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
SPTAN1	-0.022	0.046	0.22	2	-10000	0	2
RFC1	-0.019	0.046	0.22	3	-10000	0	3
PRKDC	-0.016	0.061	0.22	9	-10000	0	9
RIPK1	0.018	0.008	-10000	0	-10000	0	0
CASP7	-0.041	0.16	-10000	0	-0.65	15	15
FASLG/FAS/FADD/FAF1	0.005	0.073	0.23	7	-0.22	2	9
MAP2K4	-0.021	0.14	-10000	0	-0.37	23	23
mol:ceramide	0	0.089	-10000	0	-0.3	3	3
GSN	-0.022	0.043	0.22	1	-10000	0	1
FASLG/FAS/FADD/FAF1/Caspase 8	0.004	0.078	0.27	1	-0.29	2	3
FAS	0.014	0.016	-10000	0	-10000	0	0
BID	-0.034	0.041	-10000	0	-10000	0	0
MAP3K1	-0.036	0.14	0.23	1	-0.44	18	19
MAP3K7	0.015	0.013	-10000	0	-10000	0	0
RB1	-0.018	0.038	-10000	0	-10000	0	0
CFLAR	0.019	0.008	-10000	0	-10000	0	0
HGF/MET	-0.002	0.12	-10000	0	-0.39	22	22
ARHGDIB	-0.017	0.057	0.22	7	-10000	0	7
FADD	0.014	0.016	-10000	0	-10000	0	0
actin filament polymerization	0.022	0.043	-10000	0	-0.22	1	1
NFKB1	0	0.082	-10000	0	-0.72	1	1
MAPK8	-0.04	0.18	0.37	1	-0.51	27	28
DFFA	-0.018	0.049	0.22	4	-10000	0	4
DNA fragmentation during apoptosis	-0.017	0.048	0.22	4	-10000	0	4
FAS/FADD/MET	0.023	0.049	-10000	0	-0.3	4	4
CFLAR/RIP1	0.027	0.013	-10000	0	-10000	0	0
FAIM3	0.046	0.075	0.25	29	-10000	0	29
FAF1	0.014	0.018	-10000	0	-10000	0	0
PARP1	-0.021	0.049	0.22	3	-10000	0	3
DFFB	-0.017	0.048	0.22	4	-10000	0	4
CHUK	-0.003	0.073	-10000	0	-0.68	1	1
FASLG	0.051	0.092	0.25	42	-10000	0	42
FAS/FADD	0.02	0.022	-10000	0	-10000	0	0
HGF	-0.004	0.11	-10000	0	-0.55	10	10
LMNA	-0.023	0.057	0.19	8	-10000	0	8
CASP6	-0.021	0.045	0.22	2	-10000	0	2
CASP10	0.014	0.016	-10000	0	-10000	0	0
CASP3	-0.014	0.029	-10000	0	-10000	0	0
PTPN13	-0.008	0.12	-10000	0	-0.55	12	12
CASP8	-0.037	0.05	-10000	0	-0.18	29	29
IL6	-0.11	0.4	-10000	0	-1.2	31	31
MET	0.012	0.061	-10000	0	-0.55	3	3
ICAD/CAD	-0.016	0.065	0.42	4	-10000	0	4
FASLG/FAS/FADD/FAF1/Caspase 10	0	0.089	-10000	0	-0.3	3	3
activation of caspase activity by cytochrome c	-0.034	0.041	-10000	0	-10000	0	0
PAK2	-0.019	0.046	0.22	3	-10000	0	3
BCL2	0.019	0.004	-10000	0	-10000	0	0

×

IL2 signaling events mediated by PI3K

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	0.033	0.089	0.4	1	-0.52	1	2
UGCG	0.012	0.079	-10000	0	-0.65	3	3
AKT1/mTOR/p70S6K/Hsp90/TERT	0.049	0.11	0.32	5	-0.37	4	9
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.016	0.079	-10000	0	-0.64	3	3
mol:DAG	-0.037	0.19	-10000	0	-0.8	15	15
CaM/Ca2+/Calcineurin A alpha-beta B1	0.051	0.1	0.32	4	-0.56	1	5
FRAP1	0.051	0.12	0.34	5	-0.65	1	6
FOXO3	0.049	0.12	0.35	8	-0.5	2	10
AKT1	0.048	0.12	0.33	6	-0.54	2	8
GAB2	0.019	0.005	-10000	0	-10000	0	0
SMPD1	0.004	0.11	-10000	0	-0.61	7	7
SGMS1	-0.016	0.15	-10000	0	-0.61	15	15
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	-0.01	0.011	-10000	0	-10000	0	0
CALM1	0.018	0.004	-10000	0	-10000	0	0
cell proliferation	0.02	0.13	0.27	1	-0.46	8	9
EIF3A	0.018	0.005	-10000	0	-10000	0	0
PI3K	0.029	0.018	-10000	0	-0.17	1	1
RPS6KB1	0.024	0.079	-10000	0	-0.77	2	2
mol:sphingomyelin	-0.037	0.19	-10000	0	-0.8	15	15
natural killer cell activation	0	0.001	-10000	0	-10000	0	0
JAK3	0.037	0.062	0.26	19	-10000	0	19
PIK3R1	0.021	0.015	0.26	1	-10000	0	1
JAK1	0.019	0.005	-10000	0	-10000	0	0
NFKB1	0.019	0.001	-10000	0	-10000	0	0
MYC	0.051	0.13	-10000	0	-0.77	2	2
MYB	0.072	0.095	0.49	3	-10000	0	3
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.04	0.12	0.27	20	-0.48	3	23
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.039	0.075	-10000	0	-0.72	2	2
mol:PI-3-4-5-P3	0.04	0.11	0.27	20	-0.46	3	23
Rac1/GDP	-0.011	0.013	-10000	0	-10000	0	0
T cell proliferation	0.023	0.13	0.3	7	-0.46	4	11
SHC1	0.019	0.005	-10000	0	-10000	0	0
RAC1	0.018	0.006	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.007	0.022	0.098	14	-10000	0	14
PRKCZ	0.02	0.13	0.26	17	-0.48	4	21
NF kappa B1 p50/RelA	0.06	0.11	0.33	3	-0.56	1	4
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.031	0.091	0.25	23	-0.43	2	25
HSP90AA1	0.019	0.004	-10000	0	-10000	0	0
RELA	0.019	0.003	-10000	0	-10000	0	0
IL2RA	0.052	0.12	0.26	47	-0.55	4	51
IL2RB	0.048	0.077	0.26	31	-10000	0	31
TERT	-0.014	0.006	-10000	0	-10000	0	0
E2F1	0.07	0.083	0.34	5	-0.43	1	6
SOS1	0.019	0.005	-10000	0	-10000	0	0
RPS6	0.018	0.005	-10000	0	-10000	0	0
mol:cAMP	-0.003	0.012	-10000	0	-0.051	14	14
PTPN11	0.019	0.005	-10000	0	-10000	0	0
IL2RG	0.039	0.089	0.26	26	-0.55	2	28
actin cytoskeleton organization	0.023	0.13	0.3	7	-0.46	4	11
GRB2	0.019	0.004	-10000	0	-10000	0	0
IL2	0.016	0.004	-10000	0	-10000	0	0
PIK3CA	0.02	0.004	-10000	0	-10000	0	0
Rac1/GTP	0.034	0.019	-10000	0	-10000	0	0
LCK	0.043	0.083	0.26	28	-0.55	1	29
BCL2	0.051	0.11	0.34	2	-0.5	1	3

×

Canonical Wnt signaling pathway

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
HDAC1	0.017	0.01	-10000	0	-10000	0	0
AES	0.018	0.009	-10000	0	-10000	0	0
FBXW11	0.019	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
LRP6/FZD1	0.03	0.029	-10000	0	-10000	0	0
SMAD4	0.019	0.003	-10000	0	-10000	0	0
DKK2	0.041	0.091	0.25	29	-0.55	2	31
TLE1	0.021	0.033	0.27	4	-10000	0	4
MACF1	0.019	0.003	-10000	0	-10000	0	0
CTNNB1	0.019	0.079	0.27	2	-0.34	1	3
WIF1	0.036	0.087	0.25	34	-10000	0	34
beta catenin/RanBP3	0.004	0.065	0.33	2	-10000	0	2
KREMEN2	0.048	0.078	0.25	32	-10000	0	32
DKK1	0.03	0.17	0.25	50	-0.55	15	65
beta catenin/beta TrCP1	0.024	0.074	0.26	1	-10000	0	1
FZD1	0.025	0.039	0.25	7	-10000	0	7
AXIN2	0.007	0.1	0.55	7	-10000	0	7
AXIN1	0.019	0.003	-10000	0	-10000	0	0
RAN	0.019	0.003	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.006	0.081	-10000	0	-0.52	4	4
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.014	0.087	0.38	1	-10000	0	1
Axin1/APC/GSK3	0.018	0.076	0.27	6	-0.38	1	7
Axin1/APC/GSK3/beta catenin/Macf1	0.023	0.063	0.33	3	-10000	0	3
HNF1A	-0.012	0.12	-10000	0	-0.55	13	13
CTBP1	0.017	0.01	-10000	0	-10000	0	0
MYC	0.014	0.15	0.55	8	-1.4	1	9
RANBP3	0.019	0.003	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.065	0.08	0.33	7	-0.31	2	9
NKD1	-0.033	0.17	0.26	5	-0.55	24	29
TCF4	0.018	0.018	0.25	1	-10000	0	1
TCF3	0.018	0.018	0.25	1	-10000	0	1
WNT1/LRP6/FZD1/Axin1	0.053	0.047	0.33	1	-10000	0	1
Ran/GTP	0.014	0.002	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	-0.005	0.067	0.42	1	-10000	0	1
LEF1	0.035	0.062	0.25	19	-10000	0	19
DVL1	-0.011	0.06	-10000	0	-0.6	1	1
CSNK2A1	0.018	0.005	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.019	0.088	0.39	1	-10000	0	1
DKK1/LRP6/Kremen 2	0.05	0.13	0.33	3	-0.34	15	18
LRP6	0.018	0.005	-10000	0	-10000	0	0
CSNK1A1	0.018	0.01	-10000	0	-10000	0	0
NLK	0.019	0.004	-10000	0	-10000	0	0
CCND1	-0.001	0.14	0.64	6	-1.4	1	7
WNT1	0.032	0.068	0.25	21	-10000	0	21
GSK3A	0.019	0.005	-10000	0	-10000	0	0
GSK3B	0.019	0.002	-10000	0	-10000	0	0
FRAT1	0.018	0.005	-10000	0	-10000	0	0
PPP2R5D	0.028	0.095	0.28	24	-0.41	2	26
APC	0.003	0.065	0.28	5	-10000	0	5
WNT1/LRP6/FZD1	-0.002	0.054	-10000	0	-0.29	1	1
CREBBP	0.018	0.009	-10000	0	-10000	0	0

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.018	0.005	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.019	0.073	-10000	0	-0.24	2	2
NT3 (dimer)/TRKC	-0.023	0.16	-10000	0	-0.4	36	36
NT3 (dimer)/TRKB	-0.05	0.2	-10000	0	-0.41	55	55
SHC/Grb2/SOS1/GAB1/PI3K	0.006	0.03	-10000	0	-10000	0	0
RAPGEF1	0.019	0.004	-10000	0	-10000	0	0
BDNF	0.011	0.072	0.25	1	-0.55	4	5
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
DYNLT1	0.018	0.004	-10000	0	-10000	0	0
NTRK1	0.015	0.091	0.25	9	-0.55	5	14
NTRK2	-0.045	0.19	0.25	6	-0.55	31	37
NTRK3	0.016	0.12	0.25	17	-0.55	8	25
NT-4/5 (dimer)/TRKB	-0.015	0.16	-10000	0	-0.39	36	36
neuron apoptosis	0.014	0.12	0.48	8	-10000	0	8
SHC 2-3/Grb2	-0.013	0.14	-10000	0	-0.52	8	8
SHC1	0.018	0.004	-10000	0	-10000	0	0
SHC2	-0.029	0.12	-10000	0	-0.46	10	10
SHC3	-0.022	0.12	-10000	0	-0.52	9	9
STAT3 (dimer)	0.021	0.027	0.22	1	-0.36	1	2
NT3 (dimer)/TRKA	-0.013	0.16	-10000	0	-0.37	37	37
RIN/GDP	0.013	0.1	0.24	13	-0.26	4	17
GIPC1	0.018	0.004	-10000	0	-10000	0	0
KRAS	0.018	0.004	-10000	0	-10000	0	0
DNAJA3	-0.023	0.08	-10000	0	-0.3	15	15
RIN/GTP	0.012	0.002	-10000	0	-10000	0	0
CCND1	-0.014	0.057	0.43	1	-0.81	1	2
MAGED1	0.018	0.004	-10000	0	-10000	0	0
PTPN11	0.018	0.004	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.016	0.004	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.035	0.013	-10000	0	-10000	0	0
GRB2	0.019	0.003	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	0.036	0.079	0.33	1	-0.35	7	8
TRKA/NEDD4-2	0.019	0.079	-10000	0	-0.41	7	7
ELMO1	0.018	0.005	-10000	0	-10000	0	0
RhoG/GTP/ELMO1/DOCK1	0.023	0.009	-10000	0	-10000	0	0
NGF	0.015	0.052	0.25	1	-0.55	2	3
HRAS	0.019	0.004	-10000	0	-10000	0	0
DOCK1	0.018	0.005	-10000	0	-10000	0	0
GAB2	0.018	0.004	-10000	0	-10000	0	0
RIT2	-0.016	0.002	-10000	0	-10000	0	0
RIT1	0.018	0.004	-10000	0	-10000	0	0
FRS2	0.015	0.008	-10000	0	-10000	0	0
DNM1	0.021	0.021	0.25	2	-10000	0	2
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.018	0.005	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	0	0.083	-10000	0	-0.29	14	14
mol:GDP	0.008	0.13	0.29	13	-0.38	5	18
NGF (dimer)	0.015	0.052	0.25	1	-0.55	2	3
RhoG/GDP	0.013	0.004	-10000	0	-10000	0	0
RIT1/GDP	0.008	0.095	0.23	10	-0.25	5	15
TIAM1	0.024	0.036	0.25	6	-10000	0	6
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
BDNF (dimer)/TRKB	-0.012	0.14	-10000	0	-0.35	34	34
KIDINS220/CRKL/C3G	0.026	0.009	-10000	0	-10000	0	0
SHC/RasGAP	0.027	0.007	-10000	0	-10000	0	0
FRS2 family/SHP2	0.028	0.018	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0.043	0.018	-10000	0	-10000	0	0
RIT1/GTP	0.014	0.003	-10000	0	-10000	0	0
NT3 (dimer)	-0.042	0.19	0.25	8	-0.55	29	37
RAP1/GDP	-0.006	0.066	-10000	0	-0.22	5	5
KIDINS220/CRKL	0.018	0.005	-10000	0	-10000	0	0
BDNF (dimer)	0.011	0.072	0.25	1	-0.55	4	5
ubiquitin-dependent protein catabolic process	0.025	0.079	-10000	0	-0.35	9	9
Schwann cell development	-0.019	0.024	-10000	0	-10000	0	0
EHD4	0.019	0.003	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.034	0.024	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.015	0.055	-10000	0	-0.38	1	1
RAP1B	0.017	0.007	-10000	0	-10000	0	0
RAP1A	0.019	0.003	-10000	0	-10000	0	0
CDC42/GTP	-0.049	0.15	-10000	0	-0.34	48	48
ABL1	0.019	0.004	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.027	0.007	-10000	0	-10000	0	0
Rap1/GTP	-0.008	0.077	-10000	0	-0.56	1	1
STAT3	0.021	0.027	0.22	1	-0.36	1	2
axon guidance	-0.079	0.13	-10000	0	-0.33	48	48
MAPK3	-0.003	0.081	0.2	5	-0.32	7	12
MAPK1	-0.005	0.078	0.25	1	-0.32	7	8
CDC42/GDP	0.013	0.098	0.23	12	-0.25	5	17
NTF3	-0.042	0.19	0.25	8	-0.55	29	37
NTF4	-0.016	0.004	-10000	0	-10000	0	0
NGF (dimer)/TRKA/FAIM	0.031	0.071	-10000	0	-0.35	7	7
PI3K	0.028	0.017	-10000	0	-0.17	1	1
FRS3	0.018	0.005	-10000	0	-10000	0	0
FAIM	0.019	0.002	-10000	0	-10000	0	0
GAB1	0.019	0.003	-10000	0	-10000	0	0
RASGRF1	-0.022	0.083	-10000	0	-0.3	15	15
SOS1	0.019	0.004	-10000	0	-10000	0	0
MCF2L	-0.052	0.12	0.27	1	-0.35	35	36
RGS19	0.018	0.005	-10000	0	-10000	0	0
CDC42	0.019	0.004	-10000	0	-10000	0	0
RAS family/GTP	0.028	0.11	-10000	0	-0.38	2	2
Rac1/GDP	0.01	0.095	0.23	11	-0.25	5	16
NGF (dimer)/TRKA/GRIT	0.02	0.068	-10000	0	-0.35	7	7
neuron projection morphogenesis	-0.003	0.099	-10000	0	-0.76	1	1
NGF (dimer)/TRKA/NEDD4-2	0.026	0.08	-10000	0	-0.35	9	9
MAP2K1	-0.004	0.059	0.35	1	-10000	0	1
NGFR	0.011	0.12	0.25	13	-0.55	9	22
NGF (dimer)/TRKA/GIPC/GAIP	0.005	0.056	-10000	0	-0.26	7	7
RAS family/GTP/PI3K	0.004	0.034	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	0.038	0.028	-10000	0	-10000	0	0
NRAS	0.019	0.003	-10000	0	-10000	0	0
GRB2/SOS1	0.027	0.007	-10000	0	-10000	0	0
PRKCI	0.019	0.003	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.018	0.006	-10000	0	-10000	0	0
PRKCZ	-0.022	0.15	0.25	1	-0.55	18	19
MAPKKK cascade	-0.009	0.12	-10000	0	-0.52	10	10
RASA1	0.019	0.002	-10000	0	-10000	0	0
TRKA/c-Abl	0.024	0.068	-10000	0	-0.41	5	5
SQSTM1	0.018	0.005	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.004	0.13	-10000	0	-0.32	34	34
NGF (dimer)/TRKA/p62/Atypical PKCs	0.014	0.11	-10000	0	-0.32	20	20
MATK	0.029	0.048	0.25	11	-10000	0	11
NEDD4L	0.012	0.061	-10000	0	-0.55	3	3
RAS family/GDP	-0.025	0.048	-10000	0	-0.2	2	2
NGF (dimer)/TRKA	-0.006	0.085	-10000	0	-0.3	16	16
Rac1/GTP	-0.036	0.061	-10000	0	-0.25	8	8
FRS2 family/SHP2/CRK family	0.036	0.029	-10000	0	-10000	0	0

×

Caspase cascade in apoptosis

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
TOP1	0.015	0.078	-10000	0	-0.32	4	4
ACTA1	0.009	0.078	0.19	4	-0.32	3	7
NUMA1	0.012	0.082	-10000	0	-0.32	5	5
SPTAN1	0.003	0.079	0.27	1	-0.31	4	5
LIMK1	0.008	0.085	0.3	2	-0.31	4	6
BIRC3	0.011	0.061	-10000	0	-0.55	3	3
BIRC2	0.018	0.005	-10000	0	-10000	0	0
BAX	0.019	0.004	-10000	0	-10000	0	0
CASP10	0.007	0.055	0.2	14	-10000	0	14
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.019	0.002	-10000	0	-10000	0	0
PTK2	0.012	0.085	-10000	0	-0.33	6	6
DIABLO	0.019	0.004	-10000	0	-10000	0	0
apoptotic nuclear changes	0.003	0.079	0.27	1	-0.31	4	5
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.018	0.004	-10000	0	-10000	0	0
GSN	0.003	0.079	0.28	1	-0.31	4	5
MADD	0.019	0.004	-10000	0	-10000	0	0
TFAP2A	-0.051	0.22	-10000	0	-0.58	36	36
BID	0.011	0.035	0.13	15	-10000	0	15
MAP3K1	0.013	0.037	-10000	0	-10000	0	0
TRADD	0.018	0.005	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.026	0.009	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	0.006	0.081	0.27	1	-0.31	4	5
CASP9	0.018	0.005	-10000	0	-10000	0	0
DNA repair	0.001	0.062	0.24	7	-0.17	4	11
neuron apoptosis	0.002	0.093	-10000	0	-0.62	5	5
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.009	0.082	0.27	2	-0.31	4	6
APAF1	0.018	0.004	-10000	0	-10000	0	0
CASP6	0.013	0.09	-10000	0	-0.89	1	1
TRAF2	0.018	0.004	-10000	0	-10000	0	0
ICAD/CAD	0.003	0.085	0.38	3	-0.32	3	6
CASP7	-0.015	0.08	0.27	3	-0.25	8	11
KRT18	-0.13	0.26	-10000	0	-0.58	62	62
apoptosis	0.005	0.083	-10000	0	-0.39	2	2
DFFA	0.006	0.079	0.28	2	-0.33	3	5
DFFB	0.006	0.079	0.28	2	-0.31	4	6
PARP1	-0.001	0.062	0.17	4	-0.24	7	11
actin filament polymerization	-0.012	0.093	0.31	3	-0.32	6	9
TNF	0.025	0.045	0.25	9	-10000	0	9
CYCS	0.009	0.056	0.17	5	-0.26	5	10
SATB1	0.004	0.1	-10000	0	-0.67	2	2
SLK	0.006	0.077	-10000	0	-0.33	3	3
p15 BID/BAX	0.017	0.05	-10000	0	-0.21	3	3
CASP2	-0.005	0.055	-10000	0	-0.28	5	5
JNK cascade	-0.013	0.037	-10000	0	-10000	0	0
CASP3	0.006	0.084	-10000	0	-0.32	4	4
LMNB2	0.01	0.088	0.26	3	-0.33	7	10
RIPK1	0.018	0.005	-10000	0	-10000	0	0
CASP4	0.018	0.005	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	0.039	0.043	-10000	0	-0.32	3	3
negative regulation of DNA binding	-0.05	0.22	-10000	0	-0.57	36	36
stress fiber formation	0.003	0.078	-10000	0	-0.32	3	3
GZMB	0.018	0.08	0.2	37	-10000	0	37
CASP1	0.005	0.022	-10000	0	-0.34	1	1
LMNB1	0.026	0.088	0.27	3	-0.38	3	6
APP	0.002	0.094	-10000	0	-0.62	5	5
TNFRSF1A	0.018	0.005	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	-0.007	0.001	-10000	0	-10000	0	0
VIM	0.008	0.085	0.23	2	-0.34	4	6
LMNA	0.01	0.086	0.25	4	-0.32	6	10
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.002	0.063	-10000	0	-0.29	6	6
LRDD	0	0	-10000	0	-10000	0	0
SREBF1	0.025	0.095	0.3	3	-0.31	4	7
APAF-1/Caspase 9	-0.008	0.13	-10000	0	-0.6	11	11
nuclear fragmentation during apoptosis	0.012	0.082	-10000	0	-0.32	5	5
CFL2	0.012	0.094	0.32	6	-0.32	3	9
GAS2	-0.016	0.11	0.25	3	-0.3	16	19
positive regulation of apoptosis	0.021	0.088	0.26	4	-0.36	4	8
PRF1	0.044	0.075	0.25	29	-10000	0	29

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	-0.004	0.045	-10000	0	-0.34	1	1
BIRC5	0.13	0.12	0.25	121	-10000	0	121
NFKBIA	-0.014	0.036	0.24	2	-10000	0	2
CPEB1	-0.004	0.11	-10000	0	-0.55	10	10
AKT1	-0.014	0.035	0.24	2	-10000	0	2
NDEL1	0.018	0.006	-10000	0	-10000	0	0
Aurora A/BRCA1	-0.003	0.037	0.21	1	-10000	0	1
NDEL1/TACC3	0.015	0.054	0.23	1	-10000	0	1
GADD45A	0.016	0.036	-10000	0	-0.55	1	1
GSK3B	-0.006	0.029	-10000	0	-10000	0	0
PAK1/Aurora A	-0.004	0.038	-10000	0	-10000	0	0
MDM2	0.015	0.008	-10000	0	-10000	0	0
JUB	0	0	-10000	0	-10000	0	0
TPX2	0.066	0.083	0.38	2	-10000	0	2
TP53	-0.024	0.074	-10000	0	-10000	0	0
DLG7	-0.011	0.029	-10000	0	-10000	0	0
AURKAIP1	0.018	0.006	-10000	0	-10000	0	0
ARHGEF7	0.017	0.006	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.018	0.057	0.25	1	-10000	0	1
G2/M transition of mitotic cell cycle	-0.003	0.037	0.2	1	-10000	0	1
AURKA	-0.01	0.039	-10000	0	-10000	0	0
AURKB	0.068	0.067	0.16	86	-10000	0	86
CDC25B	-0.008	0.037	-10000	0	-0.22	4	4
G2/M transition checkpoint	-0.009	0.027	-10000	0	-10000	0	0
mRNA polyadenylation	-0.016	0.069	-10000	0	-0.32	10	10
Aurora A/CPEB	-0.016	0.07	-10000	0	-0.32	10	10
Aurora A/TACC1/TRAP/chTOG	0.008	0.049	-10000	0	-10000	0	0
BRCA1	0.021	0.021	0.25	2	-10000	0	2
centrosome duplication	-0.004	0.038	-10000	0	-10000	0	0
regulation of centrosome cycle	0.014	0.053	0.23	1	-10000	0	1
spindle assembly	0.008	0.048	-10000	0	-10000	0	0
TDRD7	0.019	0.003	-10000	0	-10000	0	0
Aurora A/RasGAP/Survivin	0.09	0.077	0.31	2	-10000	0	2
CENPA	0.07	0.079	0.16	90	-0.2	5	95
Aurora A/PP2A	-0.004	0.038	-10000	0	-10000	0	0
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	-0.001	0.039	-10000	0	-10000	0	0
negative regulation of DNA binding	-0.014	0.086	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.026	0.009	-10000	0	-10000	0	0
RASA1	0.019	0.002	-10000	0	-10000	0	0
Ajuba/Aurora A	-0.009	0.027	-10000	0	-10000	0	0
mitotic prometaphase	-0.008	0.021	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.01	0.039	-10000	0	-10000	0	0
TACC1	0.018	0.005	-10000	0	-10000	0	0
TACC3	0.038	0.065	0.25	21	-10000	0	21
Aurora A/Antizyme1	0.006	0.045	-10000	0	-10000	0	0
Aurora A/RasGAP	-0.004	0.04	-10000	0	-10000	0	0
OAZ1	0.019	0.003	-10000	0	-10000	0	0
RAN	0.019	0.003	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	-0.006	0.028	-10000	0	-10000	0	0
GIT1	0.019	0	-10000	0	-10000	0	0
GIT1/beta-PIX/PAK1	0.034	0.014	-10000	0	-10000	0	0
Importin alpha/Importin beta/TPX2	0.066	0.083	0.38	2	-10000	0	2
PPP2R5D	0.018	0.005	-10000	0	-10000	0	0
Aurora A/TPX2	0.044	0.067	0.2	5	-10000	0	5
PAK1	0.018	0.004	-10000	0	-10000	0	0
CKAP5	0.019	0.004	-10000	0	-10000	0	0

×

EPHB forward signaling

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
Ephrin A5/EPHB2	0.036	0.078	-10000	0	-0.34	6	6
cell-cell adhesion	0.008	0.023	-10000	0	-10000	0	0
Ephrin B/EPHB2/RasGAP	0.078	0.08	0.3	9	-10000	0	9
ITSN1	0.019	0.003	-10000	0	-10000	0	0
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
SHC1	0.018	0.004	-10000	0	-10000	0	0
Ephrin B1/EPHB3	0.03	0.041	-10000	0	-0.35	1	1
Ephrin B1/EPHB1	0.039	0.044	-10000	0	-10000	0	0
HRAS/GDP	0.029	0.063	0.22	2	-10000	0	2
Ephrin B/EPHB1/GRB7	0.024	0.15	0.32	6	-0.29	36	42
Endophilin/SYNJ1	0.028	0.074	0.25	14	-10000	0	14
KRAS	0.018	0.004	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	0.074	0.076	0.32	4	-10000	0	4
endothelial cell migration	0.034	0.019	-10000	0	-10000	0	0
GRB2	0.019	0.003	-10000	0	-10000	0	0
GRB7	-0.077	0.21	0.25	1	-0.55	42	43
PAK1	0.025	0.075	0.25	14	-10000	0	14
HRAS	0.019	0.004	-10000	0	-10000	0	0
RRAS	0.029	0.079	0.26	15	-10000	0	15
DNM1	0.021	0.021	0.25	2	-10000	0	2
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	0.023	0.068	0.25	9	-10000	0	9
lamellipodium assembly	-0.008	0.023	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.025	0.063	0.24	2	-10000	0	2
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
EPHB2	0.048	0.078	0.25	32	-10000	0	32
EPHB3	0.029	0.065	0.25	14	-0.55	1	15
EPHB1	0.044	0.072	0.25	27	-10000	0	27
EPHB4	0.018	0.004	-10000	0	-10000	0	0
mol:GDP	0.013	0.054	0.21	2	-10000	0	2
Ephrin B/EPHB2	0.068	0.075	0.31	7	-10000	0	7
Ephrin B/EPHB3	0.064	0.081	0.31	12	-0.3	1	13
JNK cascade	0.008	0.064	0.26	7	-10000	0	7
Ephrin B/EPHB1	0.069	0.073	0.31	5	-10000	0	5
RAP1/GDP	0.016	0.076	-10000	0	-10000	0	0
EFNB2	0.017	0.006	-10000	0	-10000	0	0
EFNB3	0.077	0.1	0.25	65	-10000	0	65
EFNB1	0.019	0.004	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	0.055	0.058	0.31	2	-10000	0	2
RAP1B	0.017	0.007	-10000	0	-10000	0	0
RAP1A	0.019	0.003	-10000	0	-10000	0	0
CDC42/GTP	0.05	0.071	0.24	7	-10000	0	7
Rap1/GTP	0	0.041	0.15	1	-10000	0	1
axon guidance	0.035	0.077	-10000	0	-0.34	6	6
MAPK3	0.018	0.059	0.22	5	-10000	0	5
MAPK1	0.016	0.065	0.26	5	-10000	0	5
Rac1/GDP	0.017	0.076	0.29	2	-10000	0	2
actin cytoskeleton reorganization	-0.012	0.035	-10000	0	-10000	0	0
CDC42/GDP	0.021	0.083	0.33	3	-10000	0	3
PI3K	0.038	0.021	-10000	0	-10000	0	0
EFNA5	0.009	0.092	0.25	4	-0.55	6	10
Ephrin B2/EPHB4	0.022	0.01	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	0.024	0.069	0.24	3	-10000	0	3
CDC42	0.019	0.004	-10000	0	-10000	0	0
RAS family/GTP	-0.004	0.036	-10000	0	-10000	0	0
PTK2	0.009	0.11	0.55	10	-10000	0	10
MAP4K4	0.008	0.065	0.27	7	-10000	0	7
SRC	0.019	0.004	-10000	0	-10000	0	0
KALRN	0.021	0.021	0.25	2	-10000	0	2
Intersectin/N-WASP	0.027	0.008	-10000	0	-10000	0	0
neuron projection morphogenesis	0.028	0.1	0.34	13	-10000	0	13
MAP2K1	0.019	0.057	0.22	2	-10000	0	2
WASL	0.018	0.005	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	0.07	0.061	0.33	3	-10000	0	3
cell migration	0.025	0.094	0.3	8	-10000	0	8
NRAS	0.019	0.003	-10000	0	-10000	0	0
SYNJ1	0.028	0.075	0.25	14	-10000	0	14
PXN	0.019	0.004	-10000	0	-10000	0	0
TF	0.034	0.08	0.25	15	-10000	0	15
HRAS/GTP	0.052	0.057	0.25	2	-10000	0	2
Ephrin B1/EPHB1-2	0.059	0.059	0.31	3	-10000	0	3
cell adhesion mediated by integrin	-0.019	0.063	-10000	0	-0.21	18	18
RAC1	0.018	0.006	-10000	0	-10000	0	0
mol:GTP	0.064	0.071	0.26	10	-10000	0	10
RAC1-CDC42/GTP	-0.011	0.032	-10000	0	-0.27	1	1
RASA1	0.019	0.002	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0.014	0.076	0.35	1	-10000	0	1
ruffle organization	0.037	0.1	0.37	13	-10000	0	13
NCK1	0.019	0.002	-10000	0	-10000	0	0
receptor internalization	0.023	0.072	0.24	14	-10000	0	14
Ephrin B/EPHB2/KALRN	0.077	0.08	0.3	9	-10000	0	9
ROCK1	-0.008	0.034	0.19	2	-0.32	1	3
RAS family/GDP	-0.02	0.027	-10000	0	-10000	0	0
Rac1/GTP	-0.004	0.031	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src/Paxillin	0.023	0.066	0.26	1	-10000	0	1

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.052	0.11	-10000	0	-0.55	1	1
RAD9A	0.019	0.003	-10000	0	-10000	0	0
AP1	0.005	0.085	-10000	0	-0.41	9	9
IFNAR2	0.019	0.004	-10000	0	-10000	0	0
AKT1	0.008	0.035	-10000	0	-0.21	5	5
ER alpha/Oestrogen	0.014	0.076	0.18	17	-0.4	6	23
NFX1/SIN3/HDAC complex	0.003	0.05	-10000	0	-0.34	2	2
EGF	-0.21	0.28	-10000	0	-0.55	101	101
SMG5	0.019	0.004	-10000	0	-10000	0	0
SMG6	0.018	0.005	-10000	0	-10000	0	0
SP3/HDAC2	0.027	0.009	-10000	0	-10000	0	0
TERT/c-Abl	-0.049	0.11	-10000	0	-10000	0	0
SAP18	0.018	0.006	-10000	0	-10000	0	0
MRN complex	0.035	0.013	-10000	0	-10000	0	0
WT1	-0.22	0.28	-10000	0	-0.55	104	104
WRN	0.018	0.004	-10000	0	-10000	0	0
SP1	0.019	0.005	-10000	0	-10000	0	0
SP3	0.019	0.003	-10000	0	-10000	0	0
TERF2IP	0.018	0.005	-10000	0	-10000	0	0
Telomerase/Nucleolin	-0.049	0.11	-10000	0	-0.49	1	1
Mad/Max	0.027	0.008	-10000	0	-10000	0	0
TERT	-0.053	0.11	-10000	0	-0.56	1	1
CCND1	-0.05	0.13	-10000	0	-1.2	1	1
MAX	0.019	0.005	-10000	0	-10000	0	0
RBBP7	0.018	0.005	-10000	0	-10000	0	0
RBBP4	0.019	0.003	-10000	0	-10000	0	0
TERF2	-0.013	0.017	-10000	0	-10000	0	0
PTGES3	0.018	0.005	-10000	0	-10000	0	0
SIN3A	0.019	0.004	-10000	0	-10000	0	0
Telomerase/911	0.009	0.062	-10000	0	-0.36	3	3
CDKN1B	0.02	0.061	0.27	2	-10000	0	2
RAD1	0.017	0.006	-10000	0	-10000	0	0
XRCC5	0.019	0.004	-10000	0	-10000	0	0
XRCC6	0.019	0.004	-10000	0	-10000	0	0
SAP30	0.019	0.004	-10000	0	-10000	0	0
TRF2/PARP2	0.025	0.012	-10000	0	-10000	0	0
UBE3A	0.019	0.004	-10000	0	-10000	0	0
JUN	0.018	0.006	-10000	0	-10000	0	0
E6	0	0.001	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.014	0.004	-10000	0	-10000	0	0
FOS	-0.004	0.11	-10000	0	-0.55	10	10
IFN-gamma/IRF1	0.061	0.069	-10000	0	-10000	0	0
PARP2	0.018	0.005	-10000	0	-10000	0	0
BLM	0.12	0.12	0.25	106	-10000	0	106
Telomerase	-0.014	0.073	-10000	0	-0.48	2	2
IRF1	0.02	0.004	-10000	0	-10000	0	0
ESR1	0.02	0.11	0.25	17	-0.55	6	23
KU/TER	0.027	0.008	-10000	0	-10000	0	0
ATM/TRF2	0.023	0.018	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.011	0.046	-10000	0	-0.28	1	1
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.011	0.047	-10000	0	-0.28	1	1
HDAC1	0.019	0.004	-10000	0	-10000	0	0
HDAC2	0.018	0.006	-10000	0	-10000	0	0
ATM	0.011	0.015	-10000	0	-10000	0	0
SMAD3	-0.013	0.011	0.14	1	-10000	0	1
ABL1	0.019	0.004	-10000	0	-10000	0	0
MXD1	0.019	0.004	-10000	0	-10000	0	0
MRE11A	0.018	0.004	-10000	0	-10000	0	0
HUS1	0.018	0.005	-10000	0	-10000	0	0
RPS6KB1	0.019	0.003	-10000	0	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.023	0.11	-10000	0	-10000	0	0
NR2F2	0.018	0.006	-10000	0	-10000	0	0
MAPK3	-0.016	0.004	-10000	0	-10000	0	0
MAPK1	-0.016	0.005	-10000	0	-10000	0	0
TGFB1/TGF beta receptor Type II	0.019	0.016	0.25	1	-10000	0	1
NFKB1	0.019	0.001	-10000	0	-10000	0	0
HNRNPC	0.018	0.004	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.011	0.015	-10000	0	-10000	0	0
NBN	0.018	0.005	-10000	0	-10000	0	0
EGFR	0.017	0.039	0.25	1	-0.55	1	2
mol:Oestrogen	0	0	-10000	0	-10000	0	0
EGF/EGFR	-0.14	0.21	-10000	0	-0.38	102	102
MYC	0.016	0.036	-10000	0	-0.55	1	1
IL2	-0.014	0.01	-10000	0	-10000	0	0
KU	0.027	0.008	-10000	0	-10000	0	0
RAD50	0.019	0.003	-10000	0	-10000	0	0
HSP90AA1	0.019	0.004	-10000	0	-10000	0	0
TGFB1	0.019	0.016	0.25	1	-10000	0	1
TRF2/BLM	0.086	0.08	0.22	9	-10000	0	9
FRAP1	0	0	-10000	0	-10000	0	0
KU/TERT	-0.043	0.12	-10000	0	-0.53	1	1
SP1/HDAC2	0.027	0.01	-10000	0	-10000	0	0
PINX1	0.018	0.004	-10000	0	-10000	0	0
Telomerase/EST1A	-0.046	0.1	-10000	0	-0.5	1	1
Smad3/Myc	-0.016	0.024	-10000	0	-0.35	1	1
911 complex	0.033	0.015	-10000	0	-10000	0	0
IFNG	0.069	0.099	0.26	56	-10000	0	56
Telomerase/PinX1	-0.048	0.11	-10000	0	-0.5	1	1
Telomerase/AKT1/mTOR/p70S6K	-0.009	0.082	-10000	0	-0.53	2	2
SIN3B	0.019	0.004	-10000	0	-10000	0	0
YWHAE	0.018	0.005	-10000	0	-10000	0	0
Telomerase/EST1B	-0.044	0.11	-10000	0	-0.5	1	1
response to DNA damage stimulus	0	0.023	-10000	0	-10000	0	0
MRN complex/TRF2/Rap1	0.045	0.022	-10000	0	-10000	0	0
TRF2/WRN	0.025	0.012	-10000	0	-10000	0	0
Telomerase/hnRNP C1/C2	-0.047	0.11	-10000	0	-0.5	1	1
E2F1	0.091	0.11	0.25	78	-10000	0	78
ZNFX1	0.019	0.004	-10000	0	-10000	0	0
PIF1	0.037	0.063	0.25	20	-10000	0	20
NCL	0.017	0.006	-10000	0	-10000	0	0
DKC1	0.019	0.003	-10000	0	-10000	0	0
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	0.02	0.049	-10000	0	-0.34	4	4
CRKL	0.01	0.095	0.3	4	-0.4	3	7
mol:PIP3	0.004	0.054	-10000	0	-0.84	1	1
AKT1	0.004	0.065	-10000	0	-0.75	1	1
PTK2B	0.018	0.004	-10000	0	-10000	0	0
RAPGEF1	0.008	0.094	0.3	3	-0.38	3	6
RANBP10	0.018	0.005	-10000	0	-10000	0	0
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
HGF/MET/SHIP2	0.015	0.086	-10000	0	-0.35	13	13
MAP3K5	0.024	0.11	0.3	7	-0.41	3	10
HGF/MET/CIN85/CBL/ENDOPHILINS	0.022	0.083	-10000	0	-0.32	13	13
AP1	-0.024	0.077	-10000	0	-0.37	9	9
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.018	0.004	-10000	0	-10000	0	0
apoptosis	-0.051	0.24	-10000	0	-0.77	24	24
STAT3 (dimer)	-0.006	0.069	-10000	0	-0.28	12	12
GAB1/CRKL/SHP2/PI3K	0.027	0.09	-10000	0	-0.38	3	3
INPP5D	0.021	0.03	0.25	4	-10000	0	4
CBL/CRK	0.016	0.089	0.43	1	-0.39	3	4
PTPN11	0.018	0.004	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.018	0.004	-10000	0	-10000	0	0
PTEN	0.017	0.006	-10000	0	-10000	0	0
ELK1	0.007	0.1	0.36	12	-10000	0	12
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.007	0.05	-10000	0	-0.22	4	4
PAK1	0.004	0.07	0.38	1	-0.71	1	2
HGF/MET/RANBP10	0.013	0.086	-10000	0	-0.35	13	13
HRAS	-0.026	0.13	-10000	0	-0.49	12	12
DOCK1	0.008	0.092	0.3	3	-0.39	3	6
GAB1	0	0.082	-10000	0	-0.42	3	3
CRK	0.007	0.092	0.35	2	-0.41	3	5
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.028	0.14	-10000	0	-0.51	15	15
JUN	0.018	0.006	-10000	0	-10000	0	0
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.008	0.053	-10000	0	-0.22	14	14
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
cell morphogenesis	0.008	0.12	0.44	6	-0.4	2	8
GRB2/SHC	0.013	0.056	-10000	0	-0.25	3	3
FOS	-0.004	0.11	-10000	0	-0.55	10	10
GLMN	0.002	0.001	-10000	0	-10000	0	0
cell motility	0.007	0.1	0.36	12	-10000	0	12
HGF/MET/MUC20	0.005	0.082	-10000	0	-0.35	13	13
cell migration	0.013	0.055	-10000	0	-0.24	3	3
GRB2	0.019	0.003	-10000	0	-10000	0	0
CBL	0.018	0.005	-10000	0	-10000	0	0
MET/RANBP10	0.02	0.049	-10000	0	-0.34	4	4
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.005	0.066	-10000	0	-0.28	12	12
MET/MUC20	0.008	0.046	-10000	0	-0.34	4	4
RAP1B	0.025	0.11	0.34	5	-0.4	2	7
RAP1A	0.004	0.089	0.3	2	-0.4	2	4
HGF/MET/RANBP9	0.014	0.086	-10000	0	-0.35	13	13
RAF1	-0.02	0.13	-10000	0	-0.47	12	12
STAT3	-0.012	0.066	-10000	0	-0.28	12	12
cell proliferation	-0.004	0.11	0.31	5	-0.39	11	16
RPS6KB1	0.001	0.033	-10000	0	-0.26	2	2
MAPK3	0.007	0.13	0.64	8	-10000	0	8
MAPK1	0.004	0.12	0.69	6	-10000	0	6
RANBP9	0.018	0.005	-10000	0	-10000	0	0
MAPK8	0.026	0.14	0.36	5	-0.4	5	10
SRC	-0.013	0.061	-10000	0	-0.27	11	11
PI3K	0.015	0.062	-10000	0	-0.25	4	4
MET/Glomulin	0.007	0.045	-10000	0	-0.35	3	3
SOS1	0.019	0.004	-10000	0	-10000	0	0
MAP2K1	-0.011	0.14	0.34	5	-0.45	11	16
MET	0.012	0.061	-10000	0	-0.55	3	3
MAP4K1	0.017	0.1	0.35	3	-0.34	6	9
PTK2	0.018	0.005	-10000	0	-10000	0	0
MAP2K2	-0.014	0.13	0.37	1	-0.47	9	10
BAD	0.001	0.064	-10000	0	-0.71	1	1
MAP2K4	0.038	0.12	0.31	10	-0.38	3	13
SHP2/GRB2/SOS1/GAB1	0.011	0.082	-10000	0	-0.38	6	6
INPPL1	0.019	0.004	-10000	0	-10000	0	0
PXN	0.019	0.004	-10000	0	-10000	0	0
SH3KBP1	0.018	0.005	-10000	0	-10000	0	0
HGS	-0.016	0.05	-10000	0	-0.21	13	13
PLCgamma1/PKC	0.014	0.003	-10000	0	-10000	0	0
HGF	-0.004	0.11	-10000	0	-0.55	10	10
RASA1	0.019	0.002	-10000	0	-10000	0	0
NCK1	0.019	0.002	-10000	0	-10000	0	0
PTPRJ	0.019	0.003	-10000	0	-10000	0	0
NCK/PLCgamma1	0.014	0.063	-10000	0	-0.23	13	13
PDPK1	0.002	0.057	-10000	0	-0.78	1	1
HGF/MET/SHIP	0.015	0.088	-10000	0	-0.35	13	13

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.018	0.007	-10000	0	-10000	0	0
HDAC2	0.017	0.008	-10000	0	-10000	0	0
GNB1/GNG2	0.028	0.065	-10000	0	-0.35	6	6
forebrain development	0.008	0.16	0.4	11	-0.44	14	25
GNAO1	-0.049	0.19	0.27	1	-0.55	31	32
SMO/beta Arrestin2	0.018	0.067	-10000	0	-0.4	6	6
SMO	0.007	0.087	-10000	0	-0.55	6	6
ARRB2	0.019	0.006	-10000	0	-10000	0	0
GLI3/SPOP	0.015	0.091	-10000	0	-0.39	6	6
mol:GTP	0.001	0.003	-10000	0	-10000	0	0
GSK3B	0.019	0.002	-10000	0	-10000	0	0
GNAI2	0.02	0.005	-10000	0	-10000	0	0
SIN3/HDAC complex	0.039	0.021	-10000	0	-10000	0	0
GNAI1	0.01	0.071	-10000	0	-0.55	4	4
XPO1	0.023	0.014	-10000	0	-10000	0	0
GLI1/Su(fu)	-0.003	0.16	0.4	5	-0.54	11	16
SAP30	0.017	0.008	-10000	0	-10000	0	0
mol:GDP	0.007	0.086	-10000	0	-0.55	6	6
MIM/GLI2A	0.028	0.034	-10000	0	-10000	0	0
IFT88	0.017	0.006	-10000	0	-10000	0	0
GNAI3	0.02	0.005	-10000	0	-10000	0	0
GLI2	0.019	0.059	0.29	3	-0.28	1	4
GLI3	0.008	0.094	0.26	1	-0.38	8	9
CSNK1D	0.018	0.005	-10000	0	-10000	0	0
CSNK1E	0.019	0.004	-10000	0	-10000	0	0
SAP18	0.017	0.008	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.017	0.006	-10000	0	-10000	0	0
GNG2	0.024	0.036	0.25	6	-10000	0	6
Gi family/GTP	-0.042	0.13	-10000	0	-0.3	44	44
SIN3B	0.017	0.007	-10000	0	-10000	0	0
SIN3A	0.017	0.007	-10000	0	-10000	0	0
GLI3/Su(fu)	-0.001	0.11	0.35	1	-0.44	10	11
GLI2/Su(fu)	0.01	0.069	-10000	0	-0.35	4	4
FOXA2	0.012	0.16	-10000	0	-0.66	9	9
neural tube patterning	0.008	0.16	0.4	11	-0.44	14	25
SPOP	0.019	0.002	-10000	0	-10000	0	0
Su(fu)/PIAS1	0.003	0.074	-10000	0	-0.44	2	2
GNB1	0.018	0.006	-10000	0	-10000	0	0
CSNK1G2	0.019	0.004	-10000	0	-10000	0	0
CSNK1G3	0.019	0.003	-10000	0	-10000	0	0
MTSS1	0.028	0.034	-10000	0	-10000	0	0
embryonic limb morphogenesis	0.008	0.16	0.4	11	-0.44	14	25
SUFU	0.005	0.052	-10000	0	-0.48	2	2
LGALS3	0.017	0.036	-10000	0	-0.55	1	1
catabolic process	0.027	0.095	0.37	1	-0.4	3	4
GLI3A/CBP	0.038	0.071	0.25	4	-0.36	3	7
KIF3A	0.019	0.003	-10000	0	-10000	0	0
GLI1	0.006	0.16	0.43	9	-0.45	14	23
RAB23	0.02	0.021	0.25	2	-10000	0	2
CSNK1A1	0.019	0.003	-10000	0	-10000	0	0
IFT172	0.019	0.004	-10000	0	-10000	0	0
RBBP7	0.017	0.008	-10000	0	-10000	0	0
Su(fu)/Galectin3	0.003	0.077	-10000	0	-0.4	3	3
GNAZ	-0.016	0.14	-10000	0	-0.55	16	16
RBBP4	0.018	0.006	-10000	0	-10000	0	0
CSNK1G1	0.019	0.004	-10000	0	-10000	0	0
PIAS1	0.018	0.004	-10000	0	-10000	0	0
PRKACA	0.018	0.005	-10000	0	-10000	0	0
GLI2/SPOP	0.027	0.054	0.31	1	-10000	0	1
STK36	0.023	0.014	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.053	0.12	-10000	0	-0.41	15	15
PTCH1	0.012	0.16	0.51	7	-0.52	1	8
MIM/GLI1	0.018	0.16	0.48	8	-0.46	9	17
CREBBP	0.038	0.071	0.25	4	-0.36	3	7
Su(fu)/SIN3/HDAC complex	-0.008	0.076	-10000	0	-0.34	7	7

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	-0.14	0.17	-10000	0	-0.45	35	35
CaM/Ca2+	0.014	0.003	-10000	0	-10000	0	0
AKT1	0.018	0.005	-10000	0	-10000	0	0
AKT2	0.018	0.005	-10000	0	-10000	0	0
STXBP4	0.019	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	-0.15	0.18	-10000	0	-0.46	41	41
YWHAZ	0.018	0.005	-10000	0	-10000	0	0
CALM1	0.018	0.004	-10000	0	-10000	0	0
YWHAQ	0.019	0.004	-10000	0	-10000	0	0
TBC1D4	-0.012	0.006	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.018	0.004	-10000	0	-10000	0	0
YWHAB	0.019	0.004	-10000	0	-10000	0	0
SNARE/Synip	0.035	0.013	-10000	0	-10000	0	0
YWHAG	0.018	0.004	-10000	0	-10000	0	0
ASIP	0.021	0.041	0.25	7	-10000	0	7
PRKCI	0.019	0.003	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0.014	0.003	-10000	0	-10000	0	0
RHOQ	0.019	0.003	-10000	0	-10000	0	0
GYS1	-0.004	0.002	-10000	0	-10000	0	0
PRKCZ	-0.022	0.15	0.25	1	-0.55	18	19
TRIP10	0.019	0.004	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.025	0.006	-10000	0	-10000	0	0
AS160/14-3-3	-0.011	0.084	-10000	0	-0.41	5	5
VAMP2	0.018	0.006	-10000	0	-10000	0	0
SLC2A4	-0.17	0.2	-10000	0	-0.52	43	43
STX4	0.019	0.004	-10000	0	-10000	0	0
GSK3B	0.009	0.004	-10000	0	-10000	0	0
SFN	-0.003	0.13	0.25	9	-0.55	13	22
LNPEP	0.021	0.021	0.25	2	-10000	0	2
YWHAE	0.018	0.005	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	-0.013	0.004	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.024	0.011	-10000	0	-10000	0	0
CDKN1B	0.002	0.054	-10000	0	-0.31	6	6
CDKN1A	0.005	0.05	-10000	0	-0.31	3	3
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.019	0.004	-10000	0	-10000	0	0
FOXO3	0.002	0.059	-10000	0	-0.31	7	7
AKT1	-0.005	0.059	-10000	0	-0.32	7	7
BAD	0.019	0.003	-10000	0	-10000	0	0
AKT3	0.005	0.022	-10000	0	-0.34	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.003	0.064	-10000	0	-0.31	7	7
AKT1/ASK1	0.015	0.067	-10000	0	-0.3	7	7
BAD/YWHAZ	0.034	0.014	-10000	0	-10000	0	0
RICTOR	0.017	0.006	-10000	0	-10000	0	0
RAF1	0.019	0.004	-10000	0	-10000	0	0
JNK cascade	-0.014	0.065	0.29	7	-10000	0	7
TSC1	-0.001	0.058	-10000	0	-0.31	7	7
YWHAZ	0.018	0.005	-10000	0	-10000	0	0
AKT1/RAF1	0.021	0.072	0.28	1	-0.31	7	8
EP300	0.019	0.004	-10000	0	-10000	0	0
mol:GDP	-0.005	0.058	-10000	0	-0.32	7	7
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	-0.002	0.06	-10000	0	-0.31	7	7
YWHAQ	0.019	0.004	-10000	0	-10000	0	0
TBC1D4	-0.004	0.002	-10000	0	-10000	0	0
MAP3K5	0.016	0.036	-10000	0	-0.55	1	1
MAPKAP1	0.019	0.003	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.002	0.089	0.37	7	-0.24	2	9
YWHAH	0.018	0.004	-10000	0	-10000	0	0
AKT1S1	0.002	0.056	-10000	0	-0.31	5	5
CASP9	0.003	0.048	-10000	0	-0.31	4	4
YWHAB	0.019	0.004	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.022	0.075	0.32	2	-0.3	7	9
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.036	0.012	-10000	0	-10000	0	0
YWHAE	0.018	0.005	-10000	0	-10000	0	0
SRC	0.019	0.004	-10000	0	-10000	0	0
AKT2/p21CIP1	0.002	0.056	0.22	1	-10000	0	1
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	-0.002	0.058	-10000	0	-0.3	8	8
CHUK	0.004	0.043	-10000	0	-0.31	3	3
BAD/BCL-XL	0.019	0.067	0.26	1	-0.3	7	8
mTORC2	0.022	0.009	-10000	0	-10000	0	0
AKT2	0.006	0.002	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.005	0.11	0.31	2	-0.42	8	10
PDPK1	0.019	0.002	-10000	0	-10000	0	0
MDM2	0.038	0.1	0.25	7	-0.31	7	14
MAPKKK cascade	-0.021	0.07	0.3	7	-0.27	1	8
MDM2/Cbp/p300	0.059	0.1	0.29	3	-10000	0	3
TSC1/TSC2	-0.003	0.065	0.24	2	-0.31	7	9
proteasomal ubiquitin-dependent protein catabolic process	0.057	0.096	0.28	3	-10000	0	3
glucose import	-0.11	0.14	0.2	1	-0.31	89	90
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.003	0.052	-10000	0	-0.39	1	1
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.11	0.14	-10000	0	-0.31	89	89
GSK3A	0.002	0.066	-10000	0	-0.31	7	7
FOXO1	0.007	0.029	-10000	0	-0.31	1	1
GSK3B	-0.001	0.061	-10000	0	-0.31	7	7
SFN	-0.003	0.13	0.25	9	-0.55	13	22
G1/S transition of mitotic cell cycle	0.003	0.072	0.3	1	-0.31	7	8
p27Kip1/14-3-3 family	-0.001	0.092	-10000	0	-0.46	6	6
PRKACA	0.018	0.005	-10000	0	-10000	0	0
KPNA1	0.019	0.002	-10000	0	-10000	0	0
HSP90AA1	0.019	0.004	-10000	0	-10000	0	0
YWHAG	0.018	0.004	-10000	0	-10000	0	0
RHEB	0.018	0.005	-10000	0	-10000	0	0
CREBBP	0.019	0.003	-10000	0	-10000	0	0

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.085	0.17	0.59	4	-0.85	1	5
CRP	0.092	0.18	0.64	5	-0.85	1	6
cell cycle arrest	0.085	0.18	0.6	4	-1	1	5
TIMP1	0.094	0.16	0.6	4	-0.64	1	5
IL6ST	0.046	0.082	0.26	27	-0.55	1	28
Rac1/GDP	0.036	0.13	0.28	1	-0.61	4	5
AP1	0.033	0.15	0.39	6	-0.52	5	11
GAB2	0.019	0.005	-10000	0	-10000	0	0
TNFSF11	0.09	0.18	0.65	3	-0.85	1	4
HSP90B1	0.044	0.093	-10000	0	-0.7	1	1
GAB1	0.019	0.003	-10000	0	-10000	0	0
MAPK14	-0.013	0.12	-10000	0	-0.53	5	5
AKT1	0.017	0.058	-10000	0	-0.34	1	1
FOXO1	0.017	0.058	-10000	0	-10000	0	0
MAP2K6	-0.004	0.12	0.33	1	-0.49	7	8
mol:GTP	0.001	0.002	-10000	0	-10000	0	0
MAP2K4	0.039	0.14	0.33	6	-0.58	4	10
MITF	0.008	0.12	0.29	3	-0.49	7	10
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.018	0.005	-10000	0	-10000	0	0
A2M	-0.024	0.21	-10000	0	-1.1	9	9
CEBPB	0.019	0.017	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.02	0.093	0.28	1	-0.49	3	4
STAT3	0.083	0.18	0.6	4	-1.1	1	5
STAT1	0.017	0.086	-10000	0	-0.72	3	3
CEBPD	0.083	0.17	0.59	3	-0.85	1	4
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
PI3K	0.029	0.017	-10000	0	-0.17	1	1
JUN	0.018	0.006	-10000	0	-10000	0	0
PIAS3/MITF	0.024	0.13	0.32	2	-0.54	5	7
MAPK11	-0.011	0.11	-10000	0	-0.52	5	5
STAT3 (dimer)/FOXO1	0.064	0.16	0.51	5	-0.71	1	6
GRB2/SOS1/GAB family	0.03	0.12	-10000	0	-0.6	3	3
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	0.006	0.12	0.2	1	-0.34	18	19
GRB2	0.019	0.004	-10000	0	-10000	0	0
JAK2	0.019	0.016	0.25	1	-10000	0	1
LBP	0.048	0.32	0.57	13	-0.9	20	33
PIK3R1	0.021	0.015	0.26	1	-10000	0	1
JAK1	0.02	0.011	-10000	0	-10000	0	0
MYC	0.086	0.18	0.64	2	-1.2	1	3
FGG	0.081	0.17	0.69	2	-0.85	1	3
macrophage differentiation	0.085	0.18	0.6	4	-1	1	5
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0.028	0.13	-10000	0	-0.35	20	20
JUNB	0.084	0.17	0.58	4	-0.81	1	5
FOS	-0.004	0.11	-10000	0	-0.55	10	10
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	0.017	0.13	0.3	4	-0.51	6	10
STAT1/PIAS1	0.044	0.13	0.36	3	-0.43	7	10
GRB2/SOS1/GAB family/SHP2/PI3K	0.016	0.06	-10000	0	-0.35	1	1
STAT3 (dimer)	0.084	0.18	0.6	4	-1.1	1	5
PRKCD	0.067	0.16	0.43	15	-0.71	2	17
IL6R	0.013	0.062	-10000	0	-0.55	3	3
SOCS3	-0.001	0.12	-10000	0	-0.61	2	2
gp130 (dimer)/JAK1/JAK1/LMO4	0.06	0.058	-10000	0	-0.36	1	1
Rac1/GTP	0.037	0.13	0.29	3	-0.61	4	7
HCK	0.03	0.05	0.26	12	-10000	0	12
MAPKKK cascade	0.025	0.12	-10000	0	-0.53	5	5
bone resorption	0.09	0.18	0.61	4	-0.79	1	5
IRF1	0.081	0.17	0.62	3	-0.85	1	4
mol:GDP	0.017	0.13	0.27	6	-0.52	6	12
SOS1	0.019	0.004	-10000	0	-10000	0	0
VAV1	0.016	0.13	0.28	6	-0.53	6	12
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.004	0.12	-10000	0	-0.63	5	5
PTPN11	0.017	0.079	-10000	0	-0.66	3	3
IL6/IL6RA	-0.013	0.14	0.19	2	-0.44	23	25
gp130 (dimer)/TYK2/TYK2/LMO4	0.055	0.054	-10000	0	-0.36	1	1
gp130 (dimer)/JAK2/JAK2/LMO4	0.055	0.055	-10000	0	-0.35	1	1
IL6	-0.029	0.17	0.26	3	-0.55	24	27
PIAS3	0.018	0.005	-10000	0	-10000	0	0
PTPRE	0.001	0.033	0.23	2	-10000	0	2
PIAS1	0.018	0.004	-10000	0	-10000	0	0
RAC1	0.018	0.006	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	0.002	0.11	-10000	0	-0.33	17	17
LMO4	0.024	0.021	0.26	1	-10000	0	1
STAT3 (dimer)/PIAS3	0.061	0.16	0.47	1	-1.1	1	2
MCL1	0.027	0.078	-10000	0	-10000	0	0

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	0.032	0.1	0.31	9	-0.36	5	14
IKBKB	0.023	0.077	0.24	4	-0.3	3	7
AKT1	0.014	0.081	0.25	10	-0.24	2	12
IKBKG	0.023	0.078	0.22	1	-0.33	4	5
CALM1	0.009	0.073	0.25	1	-0.38	2	3
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
MAP3K1	0.034	0.11	0.33	9	-0.42	4	13
MAP3K7	0.019	0.004	-10000	0	-10000	0	0
mol:Ca2+	0.01	0.075	-10000	0	-0.36	3	3
DOK1	0.019	0.004	-10000	0	-10000	0	0
AP-1	0.02	0.083	0.25	9	-0.24	2	11
LYN	0.018	0.005	-10000	0	-10000	0	0
BLNK	0.013	0.05	-10000	0	-0.55	2	2
SHC1	0.018	0.004	-10000	0	-10000	0	0
BCR complex	0.038	0.06	0.36	2	-0.41	1	3
CD22	-0.012	0.1	0.35	2	-0.33	19	21
CAMK2G	0.011	0.066	0.24	1	-0.36	2	3
CSNK2A1	0.018	0.005	-10000	0	-10000	0	0
INPP5D	0.021	0.03	0.25	4	-10000	0	4
SHC/GRB2/SOS1	-0.023	0.051	-10000	0	-0.37	3	3
GO:0007205	0.01	0.076	-10000	0	-0.37	3	3
SYK	0.014	0.05	-10000	0	-0.55	2	2
ELK1	0.012	0.083	0.27	4	-0.39	2	6
NFATC1	0.007	0.086	0.26	1	-0.4	4	5
B-cell antigen/BCR complex	0.038	0.06	0.36	2	-0.41	1	3
PAG1/CSK	0.027	0.014	-10000	0	-10000	0	0
NFKBIB	0.021	0.036	0.12	5	-0.12	4	9
HRAS	0.007	0.071	-10000	0	-0.32	3	3
NFKBIA	0.021	0.035	0.12	5	-0.12	3	8
NF-kappa-B/RelA/I kappa B beta	0.023	0.032	0.12	5	-10000	0	5
RasGAP/Csk	0.048	0.075	0.32	2	-0.31	6	8
mol:GDP	0.008	0.076	-10000	0	-0.37	3	3
PTEN	0.017	0.006	-10000	0	-10000	0	0
CD79B	0.016	0.054	0.25	2	-0.55	2	4
NF-kappa-B/RelA/I kappa B alpha	0.023	0.032	0.12	5	-10000	0	5
GRB2	0.019	0.003	-10000	0	-10000	0	0
PI3K/BCAP/CD19	0.01	0.1	0.32	3	-0.42	6	9
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
mol:IP3	0.001	0.066	-10000	0	-0.37	3	3
CSK	0.019	0.004	-10000	0	-10000	0	0
FOS	-0.002	0.097	0.27	3	-0.38	4	7
CHUK	0.011	0.1	0.22	1	-0.35	10	11
IBTK	0.019	0.004	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	0.03	0.077	-10000	0	-0.3	1	1
PTPN6	-0.016	0.1	0.35	2	-0.38	8	10
RELA	0.019	0.003	-10000	0	-10000	0	0
BCL2A1	0.023	0.031	0.13	4	-10000	0	4
VAV2	0.012	0.078	0.31	2	-0.44	2	4
ubiquitin-dependent protein catabolic process	0.021	0.035	0.12	5	-0.12	4	9
BTK	0.008	0.091	-10000	0	-0.99	2	2
CD19	0.009	0.076	0.26	7	-0.42	3	10
MAP4K1	0.036	0.062	0.25	19	-10000	0	19
CD72	0.06	0.09	0.25	45	-10000	0	45
PAG1	0.019	0.016	0.25	1	-10000	0	1
MAPK14	0.034	0.11	0.33	13	-0.38	3	16
SH3BP5	0.019	0.004	-10000	0	-10000	0	0
PIK3AP1	0.006	0.065	-10000	0	-0.38	3	3
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	0.028	0.087	0.23	1	-0.47	3	4
RAF1	0.007	0.072	0.29	1	-0.32	2	3
RasGAP/p62DOK/SHIP	0.044	0.076	0.32	3	-0.3	6	9
CD79A	0.036	0.064	0.25	20	-10000	0	20
re-entry into mitotic cell cycle	0.02	0.083	0.25	9	-0.23	3	12
RASA1	0.019	0.002	-10000	0	-10000	0	0
MAPK3	0.007	0.073	0.28	4	-0.29	1	5
MAPK1	0.012	0.078	0.32	4	-0.29	1	5
CD72/SHP1	0.026	0.14	0.3	19	-0.4	5	24
NFKB1	0.019	0.001	-10000	0	-10000	0	0
MAPK8	0.031	0.11	0.31	10	-0.38	3	13
actin cytoskeleton organization	0.019	0.09	0.29	7	-0.45	1	8
NF-kappa-B/RelA	0.046	0.063	0.22	5	-0.2	1	6
Calcineurin	0.023	0.073	-10000	0	-0.34	2	2
PI3K	-0.037	0.079	-10000	0	-0.41	5	5
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	0.007	0.068	-10000	0	-0.38	4	4
SOS1	0.019	0.004	-10000	0	-10000	0	0
Bam32/HPK1	0.041	0.13	0.46	8	-0.61	4	12
DAPP1	0.022	0.12	0.44	2	-0.68	4	6
cytokine secretion	0.008	0.082	0.25	1	-0.37	4	5
mol:DAG	0.001	0.066	-10000	0	-0.37	3	3
PLCG2	0.018	0.005	-10000	0	-10000	0	0
MAP2K1	0.009	0.077	0.29	4	-0.31	2	6
B-cell antigen/BCR complex/FcgammaRIIB	0.037	0.079	0.33	2	-0.35	6	8
mol:PI-3-4-5-P3	-0.007	0.084	0.23	8	-0.31	4	12
ETS1	0.003	0.066	-10000	0	-0.34	2	2
B-cell antigen/BCR complex/LYN/SYK/BLNK	0.047	0.076	0.32	2	-0.38	4	6
B-cell antigen/BCR complex/LYN	0.013	0.073	0.32	2	-0.4	4	6
MALT1	0.019	0.004	-10000	0	-10000	0	0
TRAF6	0.019	0.004	-10000	0	-10000	0	0
RAC1	0.015	0.084	0.28	5	-0.48	1	6
B-cell antigen/BCR complex/LYN/SYK	0.016	0.12	0.37	3	-0.47	6	9
CARD11	0.02	0.083	0.25	7	-0.3	3	10
FCGR2B	0.007	0.089	0.25	2	-0.55	6	8
PPP3CA	0.019	0.001	-10000	0	-10000	0	0
BCL10	0.019	0.004	-10000	0	-10000	0	0
IKK complex	0.017	0.045	0.14	11	-0.12	5	16
PTPRC	0.03	0.065	0.25	14	-0.55	1	15
PDPK1	0.001	0.075	0.21	13	-0.24	2	15
PPP3CB	0.018	0.006	-10000	0	-10000	0	0
PPP3CC	0.019	0.004	-10000	0	-10000	0	0
POU2F2	0.017	0.027	0.14	4	-10000	0	4

×

Signaling events mediated by PRL

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
CCNE1	0.037	0.066	0.25	21	-10000	0	21
mol:Halofuginone	0.001	0	-10000	0	-10000	0	0
ITGA1	0.017	0.036	-10000	0	-0.55	1	1
CDKN1A	-0.01	0.083	-10000	0	-0.36	12	12
PRL-3/alpha Tubulin	0.026	0.009	-10000	0	-10000	0	0
mol:Ca2+	-0.093	0.16	-10000	0	-0.41	51	51
AGT	-0.094	0.23	0.25	3	-0.55	52	55
CCNA2	0.01	0.064	-10000	0	-10000	0	0
TUBA1B	0.019	0.004	-10000	0	-10000	0	0
EGR1	0	0.044	-10000	0	-0.4	3	3
CDK2/Cyclin E1	0.025	0.093	-10000	0	-0.52	2	2
MAPK3	-0.013	0.005	-10000	0	-10000	0	0
PRL-2 /Rab GGTase beta	0.028	0.006	-10000	0	-10000	0	0
MAPK1	-0.013	0.005	-10000	0	-10000	0	0
PTP4A1	-0.015	0.033	-10000	0	-10000	0	0
PTP4A3	0.018	0.005	-10000	0	-10000	0	0
PTP4A2	0.019	0.003	-10000	0	-10000	0	0
ITGB1	-0.013	0.005	-10000	0	-10000	0	0
SRC	0.019	0.004	-10000	0	-10000	0	0
RAC1	-0.002	0.057	-10000	0	-0.36	6	6
Rab GGTase beta/Rab GGTase alpha	0.026	0.009	-10000	0	-10000	0	0
PRL-1/ATF-5	0.004	0.07	-10000	0	-10000	0	0
RABGGTA	0.018	0.005	-10000	0	-10000	0	0
BCAR1	-0.017	0.007	-10000	0	-10000	0	0
RHOC	-0.004	0.065	-10000	0	-0.36	8	8
RHOA	-0.006	0.065	-10000	0	-0.32	10	10
cell motility	0.006	0.074	-10000	0	-0.39	4	4
PRL-1/alpha Tubulin	-0.004	0.062	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	0.024	0.028	-10000	0	-0.41	1	1
ROCK1	0.004	0.071	-10000	0	-0.39	4	4
RABGGTB	0.019	0.004	-10000	0	-10000	0	0
CDK2	0.018	0.004	-10000	0	-10000	0	0
mitosis	-0.015	0.033	-10000	0	-10000	0	0
ATF5	0.03	0.05	0.25	12	-10000	0	12

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.02	0.015	0.25	1	-10000	0	1
ANTXR2	0.019	0.002	-10000	0	-10000	0	0
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.002	0	-10000	0	-10000	0	0
monocyte activation	-0.027	0.13	-10000	0	-0.37	29	29
MAP2K2	0.008	0.037	-10000	0	-0.57	1	1
MAP2K1	-0.007	0.002	-10000	0	-10000	0	0
MAP2K7	-0.006	0.002	-10000	0	-10000	0	0
MAP2K6	-0.015	0.05	-10000	0	-0.29	8	8
CYAA	-0.009	0.005	-10000	0	-10000	0	0
MAP2K4	-0.006	0.003	-10000	0	-10000	0	0
IL1B	-0.01	0.064	0.18	2	-0.32	9	11
Channel	0.024	0.01	0.16	1	-10000	0	1
NLRP1	-0.006	0.002	-10000	0	-10000	0	0
CALM1	0.018	0.004	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.009	0.078	-10000	0	-0.39	10	10
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.002	0	-10000	0	-10000	0	0
MAPK3	-0.006	0.002	-10000	0	-10000	0	0
MAPK1	-0.006	0.002	-10000	0	-10000	0	0
PGR	-0.062	0.12	0.12	1	-0.3	51	52
PA/Cellular Receptors	0.026	0.011	0.17	1	-10000	0	1
apoptosis	-0.002	0	-10000	0	-10000	0	0
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.024	0.01	0.16	1	-10000	0	1
macrophage activation	-0.01	0.004	-10000	0	-10000	0	0
TNF	0.025	0.045	0.25	9	-10000	0	9
VCAM1	-0.027	0.13	-10000	0	-0.37	29	29
platelet activation	-0.009	0.078	-10000	0	-0.39	10	10
MAPKKK cascade	-0.007	0.035	0.091	1	-0.14	4	5
IL18	-0.013	0.057	0.11	6	-0.3	9	15
negative regulation of macrophage activation	-0.002	0	-10000	0	-10000	0	0
LEF	-0.002	0	-10000	0	-10000	0	0
CASP1	-0.002	0.002	-10000	0	-10000	0	0
mol:cAMP	-0.009	0.078	-10000	0	-0.4	10	10
necrosis	-0.002	0	-10000	0	-10000	0	0
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.024	0.01	0.16	1	-10000	0	1
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.049	0.1	0.36	5	-10000	0	5
regulation of axonogenesis	-0.01	0.041	0.26	3	-10000	0	3
myoblast fusion	-0.029	0.067	0.35	2	-0.23	1	3
mol:GTP	0.023	0.048	-10000	0	-0.17	7	7
regulation of calcium-dependent cell-cell adhesion	-0.051	0.058	-10000	0	-0.22	1	1
ARF1/GTP	0.031	0.042	-10000	0	-10000	0	0
mol:GM1	0.013	0.039	-10000	0	-10000	0	0
mol:Choline	0.003	0.033	-10000	0	-10000	0	0
lamellipodium assembly	0.018	0.084	-10000	0	-0.38	6	6
MAPK3	0.035	0.067	0.2	35	-10000	0	35
ARF6/GTP/NME1/Tiam1	0.053	0.059	0.23	1	-10000	0	1
ARF1	0.019	0.004	-10000	0	-10000	0	0
ARF6/GDP	0.03	0.067	0.23	1	-0.36	2	3
ARF1/GDP	0.029	0.073	-10000	0	-0.29	4	4
ARF6	0.031	0.02	-10000	0	-10000	0	0
RAB11A	0.019	0.003	-10000	0	-10000	0	0
TIAM1	0.025	0.037	0.25	6	-10000	0	6
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.034	0.066	0.2	34	-10000	0	34
actin filament bundle formation	-0.028	0.072	0.29	4	-0.22	1	5
KALRN	0.004	0.022	-10000	0	-0.26	1	1
RAB11FIP3/RAB11A	0.027	0.007	-10000	0	-10000	0	0
RhoA/GDP	0.029	0.073	0.22	1	-0.3	4	5
NME1	0.02	0.011	-10000	0	-10000	0	0
Rac1/GDP	0.027	0.071	-10000	0	-0.3	4	4
substrate adhesion-dependent cell spreading	0.023	0.048	-10000	0	-0.17	7	7
cortical actin cytoskeleton organization	0.017	0.083	-10000	0	-0.38	6	6
RAC1	0.018	0.006	-10000	0	-10000	0	0
liver development	0.023	0.048	-10000	0	-0.17	7	7
ARF6/GTP	0.023	0.049	-10000	0	-0.17	7	7
RhoA/GTP	0.031	0.042	-10000	0	-10000	0	0
mol:GDP	0.026	0.075	0.19	33	-0.24	6	39
ARF6/GTP/RAB11FIP3/RAB11A	0.04	0.04	-10000	0	-10000	0	0
RHOA	0.019	0.004	-10000	0	-10000	0	0
PLD1	0.019	0.039	-10000	0	-10000	0	0
RAB11FIP3	0.019	0.003	-10000	0	-10000	0	0
tube morphogenesis	0.018	0.084	-10000	0	-0.38	6	6
ruffle organization	0.01	0.041	-10000	0	-0.26	3	3
regulation of epithelial cell migration	0.023	0.048	-10000	0	-0.17	7	7
PLD2	0.02	0.035	-10000	0	-10000	0	0
PIP5K1A	0.01	0.041	-10000	0	-0.26	3	3
mol:Phosphatidic acid	0.003	0.033	-10000	0	-10000	0	0
Rac1/GTP	0.017	0.084	-10000	0	-0.38	6	6

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	0.01	0.025	-10000	0	-10000	0	0
CRKL	0.018	0.005	-10000	0	-10000	0	0
Rac1/GDP	0.013	0.004	-10000	0	-10000	0	0
DOCK1	0.018	0.005	-10000	0	-10000	0	0
ITGA4	0.025	0.036	0.25	6	-10000	0	6
alpha4/beta7 Integrin/MAdCAM1	0.061	0.054	0.33	2	-10000	0	2
EPO	0.016	0.029	0.25	3	-10000	0	3
alpha4/beta7 Integrin	0.033	0.029	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.018	0.005	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.031	0.026	-10000	0	-10000	0	0
EPO/EPOR (dimer)	0.027	0.02	-10000	0	-10000	0	0
lamellipodium assembly	-0.006	0.073	-10000	0	-0.4	6	6
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
PI3K	0.028	0.017	-10000	0	-0.17	1	1
ARF6	0.018	0.004	-10000	0	-10000	0	0
JAK2	0.01	0.022	-10000	0	-10000	0	0
PXN	0.019	0.004	-10000	0	-10000	0	0
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
MADCAM1	0.039	0.073	0.25	26	-10000	0	26
cell adhesion	0.059	0.052	0.32	2	-10000	0	2
CRKL/CBL	0.025	0.01	-10000	0	-10000	0	0
ITGB1	0.019	0.004	-10000	0	-10000	0	0
SRC	-0.038	0.085	-10000	0	-0.32	19	19
ITGB7	0.021	0.021	0.25	2	-10000	0	2
RAC1	0.018	0.006	-10000	0	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.011	0.11	-10000	0	-0.35	19	19
p130Cas/Crk/Dock1	-0.041	0.072	-10000	0	-0.29	18	18
VCAM1	-0.023	0.15	-10000	0	-0.55	19	19
RHOA	0.019	0.004	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.049	0.026	-10000	0	-10000	0	0
BCAR1	-0.039	0.079	-10000	0	-0.31	19	19
EPOR	0.018	0.005	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.018	0.005	-10000	0	-10000	0	0
GIT1	0.019	0	-10000	0	-10000	0	0
Rac1/GTP	-0.006	0.075	-10000	0	-0.43	5	5

×

IL1-mediated signaling events

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
UBC13/UEV1A	0.014	0.004	-10000	0	-10000	0	0
PRKCZ	-0.022	0.15	0.25	1	-0.55	18	19
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.018	0.005	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	0	0.063	-10000	0	-0.34	4	4
IRAK/TOLLIP	0.017	0.012	0.18	1	-10000	0	1
IKBKB	0.019	0.004	-10000	0	-10000	0	0
IKBKG	0.019	0.004	-10000	0	-10000	0	0
IL1 alpha/IL1R2	0.057	0.096	0.36	1	-0.39	5	6
IL1A	0.07	0.1	0.25	61	-10000	0	61
IL1B	-0.025	0.081	-10000	0	-0.4	10	10
IRAK/TRAF6/p62/Atypical PKCs	0.015	0.087	-10000	0	-0.29	14	14
IL1R2	0.008	0.08	0.25	1	-0.55	5	6
IL1R1	0.014	0.05	-10000	0	-0.55	2	2
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.013	0.074	-10000	0	-0.36	5	5
TOLLIP	0.019	0.004	-10000	0	-10000	0	0
TICAM2	0.019	0.005	-10000	0	-10000	0	0
MAP3K3	0.019	0.003	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.013	0.003	-10000	0	-10000	0	0
IKK complex/ELKS	-0.01	0.092	-10000	0	-0.48	2	2
JUN	-0.017	0.059	-10000	0	-0.26	8	8
MAP3K7	0.019	0.004	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.03	0.083	-10000	0	-0.33	11	11
IL1 alpha/IL1R1/IL1RAP/MYD88	0.075	0.071	0.33	1	-0.29	2	3
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.074	0.069	0.32	1	-0.28	2	3
IL1 beta fragment/IL1R1/IL1RAP	0.014	0.082	-10000	0	-0.35	11	11
NFKB1	0.019	0.001	-10000	0	-10000	0	0
MAPK8	-0.013	0.064	-10000	0	-0.28	7	7
IRAK1	-0.01	0.014	0.2	1	-10000	0	1
IL1RN/IL1R1	0.033	0.062	-10000	0	-0.41	3	3
IRAK4	0.019	0.004	-10000	0	-10000	0	0
PRKCI	0.019	0.003	-10000	0	-10000	0	0
TRAF6	0.019	0.004	-10000	0	-10000	0	0
PI3K	0.028	0.017	-10000	0	-0.17	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.001	0.073	-10000	0	-0.33	7	7
CHUK	0.018	0.005	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.014	0.082	-10000	0	-0.35	11	11
IL1 beta/IL1R2	0.003	0.094	-10000	0	-0.36	14	14
IRAK/TRAF6/TAK1/TAB1/TAB2	0.022	0.009	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.019	0.076	-10000	0	-0.32	11	11
IRAK3	0.018	0.005	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.026	0.081	-10000	0	-0.32	11	11
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.023	0.054	-10000	0	-0.26	1	1
IL1 alpha/IL1R1/IL1RAP	0.069	0.074	0.33	1	-0.32	2	3
RELA	0.019	0.003	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.018	0.005	-10000	0	-10000	0	0
MYD88	0.019	0.003	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0.027	0.015	-10000	0	-10000	0	0
IL1RAP	0.022	0.026	0.25	3	-10000	0	3
UBE2N	0.018	0.005	-10000	0	-10000	0	0
IRAK/TRAF6	-0.037	0.06	-10000	0	-0.3	10	10
CASP1	0.016	0.036	-10000	0	-0.55	1	1
IL1RN/IL1R2	0.028	0.08	-10000	0	-0.41	6	6
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.022	0.081	-10000	0	-0.33	11	11
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.017	0.068	-10000	0	-0.32	5	5
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
IL1RN	0.033	0.069	0.25	17	-0.55	1	18
TRAF6/TAK1/TAB1/TAB2	0.025	0.01	-10000	0	-10000	0	0
MAP2K6	-0.011	0.068	-10000	0	-0.29	8	8

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.019	0.004	-10000	0	-10000	0	0
NFATC1	-0.027	0.12	-10000	0	-0.46	10	10
NFATC2	-0.017	0.086	0.17	1	-0.27	12	13
NFATC3	-0.028	0.12	-10000	0	-0.38	24	24
YWHAE	0.018	0.005	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.007	0.077	-10000	0	-0.38	5	5
Exportin 1/Ran/NUP214	0.036	0.011	-10000	0	-10000	0	0
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	0.015	0.084	0.26	1	-0.36	4	5
BCL2/BAX	0.026	0.008	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0.012	0.01	-10000	0	-10000	0	0
CaM/Ca2+	0.012	0.01	-10000	0	-10000	0	0
BAX	0.019	0.004	-10000	0	-10000	0	0
MAPK14	0.016	0.01	-10000	0	-10000	0	0
BAD	0.019	0.003	-10000	0	-10000	0	0
CABIN1/MEF2D	0	0.077	-10000	0	-0.37	5	5
Calcineurin A alpha-beta B1/BCL2	0.018	0.004	-10000	0	-10000	0	0
FKBP8	0.019	0.003	-10000	0	-10000	0	0
activation-induced cell death of T cells	0	0.076	0.36	5	-10000	0	5
KPNB1	0.019	0.002	-10000	0	-10000	0	0
KPNA2	0.019	0.003	-10000	0	-10000	0	0
XPO1	0.019	0.003	-10000	0	-10000	0	0
SFN	-0.003	0.13	0.25	9	-0.55	13	22
MAP3K8	0.016	0.01	-10000	0	-10000	0	0
NFAT4/CK1 alpha	-0.014	0.079	-10000	0	-0.26	18	18
MEF2D/NFAT1/Cbp/p300	-0.009	0.11	-10000	0	-0.33	14	14
CABIN1	-0.007	0.078	-10000	0	-0.38	5	5
CALM1	0.016	0.01	-10000	0	-10000	0	0
RAN	0.019	0.003	-10000	0	-10000	0	0
MAP3K1	0.019	0.003	-10000	0	-10000	0	0
CAMK4	0.034	0.059	0.25	17	-10000	0	17
mol:Ca2+	-0.001	0.004	-10000	0	-10000	0	0
MAPK3	0.019	0.004	-10000	0	-10000	0	0
YWHAH	0.018	0.004	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.03	0.043	-10000	0	-0.41	1	1
YWHAB	0.019	0.004	-10000	0	-10000	0	0
MAPK8	0.014	0.037	-10000	0	-0.55	1	1
MAPK9	0.018	0.005	-10000	0	-10000	0	0
YWHAG	0.018	0.004	-10000	0	-10000	0	0
FKBP1A	0.018	0.004	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	-0.028	0.14	-10000	0	-0.41	21	21
PRKCH	0.019	0.004	-10000	0	-10000	0	0
CABIN1/Cbp/p300	0.024	0.018	-10000	0	-10000	0	0
CASP3	0.016	0.009	-10000	0	-10000	0	0
PIM1	0.018	0.005	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.011	0.007	-10000	0	-10000	0	0
apoptosis	0.008	0.02	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	-0.011	0.066	-10000	0	-0.33	4	4
PRKCB	0.013	0.063	0.25	1	-0.55	3	4
PRKCE	0.019	0.003	-10000	0	-10000	0	0
JNK2/NFAT4	-0.032	0.12	-10000	0	-0.35	26	26
BAD/BCL-XL	0.027	0.007	-10000	0	-10000	0	0
PRKCD	0.019	0.003	-10000	0	-10000	0	0
NUP214	0.019	0.003	-10000	0	-10000	0	0
PRKCZ	-0.024	0.15	0.25	1	-0.55	18	19
PRKCA	0.019	0.004	-10000	0	-10000	0	0
PRKCG	0.025	0.057	0.25	14	-10000	0	14
PRKCQ	0.009	0.083	0.25	3	-0.55	5	8
FKBP38/BCL2	0.027	0.007	-10000	0	-10000	0	0
EP300	0.016	0.012	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.018	0.005	-10000	0	-10000	0	0
NFATc/JNK1	-0.019	0.12	0.28	1	-0.44	10	11
CaM/Ca2+/FKBP38	0.022	0.013	-10000	0	-10000	0	0
FKBP12/FK506	0.014	0.003	-10000	0	-10000	0	0
CSNK1A1	-0.012	0.006	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0.032	0.039	-10000	0	-10000	0	0
NFATc/ERK1	-0.015	0.12	0.28	1	-0.44	10	11
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	0.019	0.084	0.26	1	-0.36	4	5
NR4A1	-0.039	0.14	0.24	1	-0.52	16	17
GSK3B	0.017	0.009	-10000	0	-10000	0	0
positive T cell selection	-0.028	0.12	-10000	0	-0.38	24	24
NFAT1/CK1 alpha	-0.014	0.064	-10000	0	-0.28	5	5
RCH1/ KPNB1	0.028	0.005	-10000	0	-10000	0	0
YWHAQ	0.019	0.004	-10000	0	-10000	0	0
PRKACA	0.016	0.01	-10000	0	-10000	0	0
AKAP5	0.026	0.058	0.25	10	-0.55	1	11
MEF2D	0.016	0.012	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.018	0.005	-10000	0	-10000	0	0
NFATc/p38 alpha	-0.016	0.12	-10000	0	-0.44	10	10
CREBBP	0.016	0.012	-10000	0	-10000	0	0
BCL2	0.018	0.004	-10000	0	-10000	0	0

×

Syndecan-3-mediated signaling 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
CTTN	0.019	0.004	-10000	0	-10000	0	0
Syndecan-3/Src/Cortactin	0.028	0.089	-10000	0	-0.38	3	3
Syndecan-3/Neurocan	0.025	0.069	0.26	1	-0.38	4	5
POMC	0.007	0.089	0.25	2	-0.55	6	8
EGFR	0.016	0.039	0.25	1	-0.55	1	2
Syndecan-3/EGFR	0.013	0.053	-10000	0	-0.36	4	4
AGRP	-0.001	0.017	-10000	0	-10000	0	0
NCSTN	0.018	0.005	-10000	0	-10000	0	0
PSENEN	0.018	0.005	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
APH1B	0.019	0.004	-10000	0	-10000	0	0
APH1A	0.018	0.005	-10000	0	-10000	0	0
NCAN	0.027	0.066	0.25	19	-10000	0	19
long-term memory	0.029	0.055	-10000	0	-0.38	3	3
Syndecan-3/IL8	0.02	0.087	0.26	1	-0.33	10	11
PSEN1	0.018	0.005	-10000	0	-10000	0	0
Src/Cortactin	0.027	0.008	-10000	0	-10000	0	0
FYN	0.018	0.005	-10000	0	-10000	0	0
limb bud formation	-0.001	0.051	-10000	0	-0.4	4	4
MC4R	-0.016	0.003	-10000	0	-10000	0	0
SRC	0.019	0.004	-10000	0	-10000	0	0
PTN	0.005	0.13	0.25	14	-0.55	12	26
FGFR/FGF/Syndecan-3	-0.001	0.052	-10000	0	-0.41	4	4
neuron projection morphogenesis	-0.006	0.089	0.37	1	-0.36	3	4
Syndecan-3/AgRP	0.013	0.056	-10000	0	-0.39	4	4
Syndecan-3/AgRP/MC4R	0.025	0.059	-10000	0	-0.38	4	4
Fyn/Cortactin	0.027	0.008	-10000	0	-10000	0	0
SDC3	-0.001	0.052	-10000	0	-0.41	4	4
GO:0007205	0	0	-10000	0	-10000	0	0
positive regulation of leukocyte migration	0.02	0.086	0.26	1	-0.32	10	11
IL8	0.024	0.11	0.25	21	-0.55	6	27
Syndecan-3/Fyn/Cortactin	0.03	0.056	-10000	0	-0.38	3	3
Syndecan-3/CASK	-0.002	0.052	-10000	0	-0.36	5	5
alpha-MSH/MC4R	0.015	0.068	0.19	2	-0.41	6	8
Gamma Secretase	0.044	0.026	-10000	0	-10000	0	0

×

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

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
BAG4	0.018	0.005	-10000	0	-10000	0	0
Caspase 8 (4 units)	0.031	0.064	-10000	0	-0.24	1	1
NEF	0.015	0.031	-10000	0	-10000	0	0
NFKBIA	0.018	0.016	-10000	0	-10000	0	0
BIRC3	-0.014	0.076	-10000	0	-0.6	3	3
CYCS	0.022	0.066	0.27	4	-0.24	1	5
RIPK1	0.018	0.005	-10000	0	-10000	0	0
CD247	0.047	0.08	0.32	18	-10000	0	18
MAP2K7	0.025	0.11	-10000	0	-0.99	1	1
protein ubiquitination	0.001	0.1	0.37	2	-0.36	9	11
CRADD	0.018	0.004	-10000	0	-10000	0	0
DAXX	0.018	0.004	-10000	0	-10000	0	0
FAS	0.018	0.005	-10000	0	-10000	0	0
BID	0.023	0.064	0.22	3	-0.24	1	4
NF-kappa-B/RelA/I kappa B alpha	0.035	0.042	0.28	1	-0.31	3	4
TRADD	0.018	0.005	-10000	0	-10000	0	0
MAP3K5	0.016	0.036	-10000	0	-0.55	1	1
CFLAR	0.019	0.003	-10000	0	-10000	0	0
FADD	0.019	0.003	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.036	0.042	0.28	1	-0.31	3	4
MAPK8	0.027	0.11	0.31	1	-0.88	1	2
APAF1	0.019	0.004	-10000	0	-10000	0	0
TRAF1	0.022	0.026	0.25	3	-10000	0	3
TRAF2	0.018	0.004	-10000	0	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.029	0.064	0.24	3	-0.25	1	4
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	-0.01	0.11	-10000	0	-0.43	11	11
CHUK	-0.001	0.1	0.26	1	-0.39	9	10
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.042	0.035	-10000	0	-0.31	1	1
TCRz/NEF	0.05	0.086	0.32	18	-10000	0	18
TNF	0.025	0.045	0.25	9	-10000	0	9
FASLG	0.047	0.13	0.33	42	-10000	0	42
NFKB1	0.019	0.015	-10000	0	-10000	0	0
TNFR1A/BAG4/TNF-alpha	0.038	0.03	-10000	0	-10000	0	0
CASP6	0.021	0.11	-10000	0	-0.5	6	6
CASP7	0.01	0.13	0.29	5	-0.46	8	13
RELA	0.018	0.016	-10000	0	-10000	0	0
CASP2	0.018	0.004	-10000	0	-10000	0	0
CASP3	0.014	0.12	0.29	5	-0.49	6	11
TNFRSF1A	0.018	0.005	-10000	0	-10000	0	0
TNFR1A/BAG4	0.026	0.009	-10000	0	-10000	0	0
CASP8	0.019	0.003	-10000	0	-10000	0	0
CASP9	0.018	0.005	-10000	0	-10000	0	0
MAP3K14	-0.005	0.11	-10000	0	-0.4	12	12
APAF-1/Caspase 9	-0.007	0.072	-10000	0	-0.43	3	3
BCL2	0.026	0.1	0.3	1	-0.78	1	2

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	0.024	0.008	-10000	0	-10000	0	0
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0.018	0.005	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.001	0.099	-10000	0	-0.55	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.017	0.007	-10000	0	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.014	0.029	-10000	0	-0.18	1	1
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.018	0.005	-10000	0	-10000	0	0
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	0.019	0.003	-10000	0	-10000	0	0
FYN	0.018	0.005	-10000	0	-10000	0	0
MAP3K12	0.019	0.004	-10000	0	-10000	0	0
FGR	0.019	0.004	-10000	0	-10000	0	0
p38 alpha/TAB1	-0.021	0.068	-10000	0	-0.34	7	7
PRKG1	0.028	0.064	0.25	13	-0.55	1	14
DUSP8	0.012	0.061	-10000	0	-0.55	3	3
PGK/cGMP/p38 alpha	0.028	0.093	0.21	5	-0.42	4	9
apoptosis	-0.02	0.065	-10000	0	-0.32	7	7
RAL/GTP	0.024	0.008	-10000	0	-10000	0	0
LYN	0.018	0.005	-10000	0	-10000	0	0
DUSP1	0.019	0.004	-10000	0	-10000	0	0
PAK1	0.018	0.004	-10000	0	-10000	0	0
SRC	0.019	0.004	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.038	0.022	-10000	0	-10000	0	0
TRAF6	0.019	0.004	-10000	0	-10000	0	0
RAC1	0.018	0.006	-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	0.018	0.005	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0.023	0.009	-10000	0	-10000	0	0
MAPK11	0.028	0.12	0.28	7	-0.41	5	12
BLK	0.036	0.076	0.25	27	-10000	0	27
HCK	0.03	0.05	0.25	12	-10000	0	12
MAP2K3	0.017	0.007	-10000	0	-10000	0	0
DUSP16	0.018	0.005	-10000	0	-10000	0	0
DUSP10	0.021	0.026	0.25	3	-10000	0	3
TRAF6/MEKK3	0.024	0.006	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.032	0.1	0.23	8	-0.42	5	13
positive regulation of innate immune response	0.036	0.13	0.3	8	-0.45	6	14
LCK	0.042	0.083	0.25	28	-0.55	1	29
p38alpha-beta/MKP7	0.036	0.12	0.27	5	-0.5	4	9
p38alpha-beta/MKP5	0.041	0.12	0.29	5	-0.5	4	9
PGK/cGMP	0.02	0.044	0.18	13	-0.4	1	14
PAK2	0.019	0.004	-10000	0	-10000	0	0
p38alpha-beta/MKP1	0.04	0.13	0.34	4	-0.46	5	9
CDC42	0.019	0.004	-10000	0	-10000	0	0
RALB	0.019	0.003	-10000	0	-10000	0	0
RALA	0.018	0.005	-10000	0	-10000	0	0
PAK3	0.062	0.098	0.25	52	-10000	0	52

×

TCGA08_rtk_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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.026	0.16	0.25	5	-0.55	22	27
HRAS	0.019	0.004	-10000	0	-10000	0	0
EGFR	0.016	0.039	0.25	1	-0.55	1	2
AKT	0.028	0.065	0.26	3	-0.28	1	4
FOXO3	0.019	0.004	-10000	0	-10000	0	0
AKT1	0.018	0.005	-10000	0	-10000	0	0
FOXO1	0.017	0.007	-10000	0	-10000	0	0
AKT3	0.016	0.036	-10000	0	-0.55	1	1
FOXO4	0.019	0.004	-10000	0	-10000	0	0
MET	0.012	0.061	-10000	0	-0.55	3	3
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
PIK3CB	0.019	0.002	-10000	0	-10000	0	0
NRAS	0.019	0.003	-10000	0	-10000	0	0
PIK3CG	0.03	0.052	0.25	13	-10000	0	13
PIK3R3	0.019	0.003	-10000	0	-10000	0	0
PIK3R2	0.019	0.003	-10000	0	-10000	0	0
NF1	0.019	0.004	-10000	0	-10000	0	0
RAS	-0.01	0.066	0.18	2	-0.19	26	28
ERBB2	0.001	0.099	-10000	0	-0.55	8	8
proliferation/survival/translation	-0.019	0.072	0.35	5	-10000	0	5
PI3K	0.013	0.068	0.27	4	-0.18	6	10
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
KRAS	0.018	0.004	-10000	0	-10000	0	0
FOXO	0.044	0.049	0.22	6	-10000	0	6
AKT2	0.018	0.005	-10000	0	-10000	0	0
PTEN	0.017	0.006	-10000	0	-10000	0	0

×

Arf6 trafficking events

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
SLC2A4	-0.22	0.28	-10000	0	-0.55	106	106
CLTC	0.005	0.082	-10000	0	-0.42	8	8
calcium ion-dependent exocytosis	0.001	0.049	0.19	1	-0.32	4	5
Dynamin 2/GTP	0.014	0.005	-10000	0	-10000	0	0
EXOC4	0.018	0.005	-10000	0	-10000	0	0
CD59	-0.001	0.058	-10000	0	-0.36	6	6
CPE	-0.009	0.03	0.14	5	-0.35	1	6
CTNNB1	0.019	0.003	-10000	0	-10000	0	0
membrane fusion	0.002	0.01	-10000	0	-10000	0	0
CTNND1	-0.013	0.029	0.17	6	-10000	0	6
DNM2	0.018	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.004	0.059	0.26	1	-0.3	4	5
TSHR	0.004	0.047	0.14	25	-10000	0	25
INS	-0.005	0.096	-10000	0	-0.49	9	9
BIN1	0.019	0.003	-10000	0	-10000	0	0
mol:Choline	0.002	0.01	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	-0.011	0.003	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.018	0.004	-10000	0	-10000	0	0
mol:Ca2+	0.014	0.005	-10000	0	-10000	0	0
JUP	-0.002	0.066	-10000	0	-0.38	7	7
ASAP2/amphiphysin II	0.034	0.012	-10000	0	-10000	0	0
ARF6/GTP	0.014	0.003	-10000	0	-10000	0	0
CDH1	-0.087	0.13	-10000	0	-0.46	8	8
clathrin-independent pinocytosis	0.014	0.003	-10000	0	-10000	0	0
MAPK8IP3	0.02	0.015	0.25	1	-10000	0	1
positive regulation of endocytosis	0.014	0.003	-10000	0	-10000	0	0
EXOC2	0.018	0.005	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	-0.006	0.058	-10000	0	-0.37	3	3
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.019	0.002	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.056	0.11	0.4	8	-10000	0	8
positive regulation of phagocytosis	-0.01	0.004	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.025	0.011	-10000	0	-10000	0	0
ACAP1	0.013	0.03	-10000	0	-0.24	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	-0.034	0.097	-10000	0	-0.39	6	6
clathrin heavy chain/ACAP1	0.004	0.076	-10000	0	-0.36	8	8
JIP4/KLC1	0.034	0.011	-10000	0	-10000	0	0
EXOC1	0.019	0.003	-10000	0	-10000	0	0
exocyst	-0.006	0.058	-10000	0	-0.38	3	3
RALA/GTP	0.013	0.004	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.025	0.006	-10000	0	-10000	0	0
receptor recycling	0.014	0.003	-10000	0	-10000	0	0
CTNNA1	-0.013	0.027	0.17	5	-10000	0	5
NME1	-0.011	0.003	-10000	0	-10000	0	0
clathrin coat assembly	0.006	0.082	-10000	0	-0.41	8	8
IL2RA	0.009	0.075	0.22	1	-0.39	6	7
VAMP3	-0.011	0.004	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.1	0.14	-10000	0	-0.38	10	10
EXOC6	0.018	0.005	-10000	0	-10000	0	0
PLD1	0.004	0.009	-10000	0	-10000	0	0
PLD2	0.004	0.008	-10000	0	-10000	0	0
EXOC5	0.019	0.004	-10000	0	-10000	0	0
PIP5K1C	0.002	0.052	-10000	0	-0.33	3	3
SDC1	-0.003	0.065	-10000	0	-0.39	6	6
ARF6/GDP	0.015	0.004	-10000	0	-10000	0	0
EXOC7	0.019	0.003	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.057	0.11	-10000	0	-0.42	8	8
mol:Phosphatidic acid	0.002	0.01	-10000	0	-10000	0	0
endocytosis	-0.032	0.011	-10000	0	-10000	0	0
SCAMP2	0.019	0.004	-10000	0	-10000	0	0
ADRB2	0.008	0.084	0.27	2	-0.4	8	10
EXOC3	0.017	0.007	-10000	0	-10000	0	0
ASAP2	0.019	0.004	-10000	0	-10000	0	0
Dynamin 2/GDP	0.017	0.007	-10000	0	-10000	0	0
KLC1	0.018	0.005	-10000	0	-10000	0	0
AVPR2	-0.016	0.11	0.28	1	-0.37	9	10
RALA	0.018	0.005	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.057	0.11	-10000	0	-0.42	7	7

×

PDGFR-beta signaling pathway

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
S1P1/Sphingosine-1-phosphate	0.058	0.086	0.28	9	-0.31	2	11
PDGFB-D/PDGFRB/SLAP	0.034	0.032	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/APS/CBL	0.037	0.019	-10000	0	-10000	0	0
AKT1	-0.01	0.081	0.46	3	-10000	0	3
mol:PI-4-5-P2	0	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.067	0.093	0.3	9	-0.35	2	11
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
FGR	0.001	0.092	-10000	0	-0.44	8	8
mol:Ca2+	0.032	0.076	0.28	4	-0.39	2	6
MYC	0.049	0.11	0.39	6	-0.8	1	7
SHC1	0.018	0.004	-10000	0	-10000	0	0
HRAS/GDP	-0.001	0.038	-10000	0	-10000	0	0
LRP1/PDGFRB/PDGFB	0.039	0.03	0.33	1	-10000	0	1
GRB10	0.018	0.005	-10000	0	-10000	0	0
PTPN11	0.018	0.004	-10000	0	-10000	0	0
GO:0007205	0.032	0.076	0.3	3	-0.4	2	5
PTEN	0.017	0.006	-10000	0	-10000	0	0
GRB2	0.019	0.003	-10000	0	-10000	0	0
GRB7	-0.077	0.21	0.25	1	-0.55	42	43
PDGFB-D/PDGFRB/SHP2	0.029	0.013	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB10	0.028	0.013	0.19	1	-10000	0	1
cell cycle arrest	0.033	0.031	-10000	0	-10000	0	0
HRAS	0.019	0.004	-10000	0	-10000	0	0
HIF1A	-0.011	0.075	0.44	3	-10000	0	3
GAB1	0.039	0.085	0.34	2	-0.42	1	3
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	0.044	0.091	0.3	11	-0.34	1	12
PDGFB-D/PDGFRB	0.037	0.018	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.029	0.013	-10000	0	-10000	0	0
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.054	0.084	0.3	8	-10000	0	8
positive regulation of MAPKKK cascade	0.029	0.013	-10000	0	-10000	0	0
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
mol:IP3	0.032	0.077	0.3	3	-0.4	2	5
E5	0	0.001	-10000	0	-10000	0	0
CSK	0.015	0.011	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.041	0.16	-10000	0	-0.39	43	43
SHB	0.018	0.005	-10000	0	-10000	0	0
BLK	0.018	0.086	0.29	2	-0.44	4	6
PTPN2	0.019	0.006	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.029	0.012	-10000	0	-10000	0	0
BCAR1	0.018	0.005	-10000	0	-10000	0	0
VAV2	0.041	0.089	0.32	3	-0.4	1	4
CBL	0.018	0.005	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.029	0.012	-10000	0	-10000	0	0
LCK	0.019	0.1	0.3	3	-0.53	5	8
PDGFRB	0.021	0.016	0.26	1	-10000	0	1
ACP1	0.018	0.005	-10000	0	-10000	0	0
HCK	0.018	0.055	0.3	1	-0.4	1	2
ABL1	0.035	0.085	0.26	7	-0.36	3	10
PDGFB-D/PDGFRB/CBL	0.037	0.088	0.31	2	-0.44	2	4
PTPN1	0.019	0.007	-10000	0	-10000	0	0
SNX15	0.019	0.003	-10000	0	-10000	0	0
STAT3	0.019	0.001	-10000	0	-10000	0	0
STAT1	0.02	0.015	0.25	1	-10000	0	1
cell proliferation	0.049	0.11	0.38	7	-0.7	1	8
SLA	0.026	0.041	0.25	8	-10000	0	8
actin cytoskeleton reorganization	-0.008	0.055	0.32	1	-10000	0	1
SRC	0.013	0.049	-10000	0	-0.4	1	1
PI3K	-0.029	0.033	-10000	0	-0.28	3	3
PDGFB-D/PDGFRB/GRB7/SHC	-0.024	0.14	-10000	0	-0.35	39	39
SH2B2	0.019	0.015	0.25	1	-10000	0	1
PLCgamma1/SPHK1	0.068	0.094	0.31	9	-0.36	2	11
LYN	0.008	0.07	-10000	0	-0.43	4	4
LRP1	0.023	0.033	0.25	5	-10000	0	5
SOS1	0.019	0.004	-10000	0	-10000	0	0
STAT5B	0.019	0.002	-10000	0	-10000	0	0
STAT5A	0.019	0.001	-10000	0	-10000	0	0
NCK1-2/p130 Cas	0.048	0.029	-10000	0	-10000	0	0
SPHK1	0.078	0.1	0.25	64	-10000	0	64
EDG1	0.002	0.003	-10000	0	-10000	0	0
mol:DAG	0.032	0.077	0.3	3	-0.4	2	5
PLCG1	0.032	0.078	0.3	3	-0.41	2	5
NHERF/PDGFRB	0.032	0.051	-10000	0	-0.35	4	4
YES1	-0.005	0.1	-10000	0	-0.45	10	10
cell migration	0.032	0.05	-10000	0	-0.35	4	4
SHC/Grb2/SOS1	0.047	0.029	-10000	0	-10000	0	0
SLC9A3R2	0.019	0.003	-10000	0	-10000	0	0
SLC9A3R1	0.01	0.071	-10000	0	-0.55	4	4
NHERF1-2/PDGFRB/PTEN	0.037	0.05	-10000	0	-0.32	4	4
FYN	0.008	0.065	-10000	0	-0.38	4	4
DOK1	-0.014	0.011	-10000	0	-10000	0	0
HRAS/GTP	0.014	0.003	-10000	0	-10000	0	0
PDGFB	0.018	0.004	-10000	0	-10000	0	0
RAC1	0.047	0.1	0.36	7	-0.38	2	9
PRKCD	-0.008	0.033	0.17	7	-10000	0	7
FER	-0.01	0.029	0.17	5	-10000	0	5
MAPKKK cascade	0.005	0.073	0.34	3	-10000	0	3
RASA1	-0.009	0.031	0.18	1	-10000	0	1
NCK1	0.019	0.002	-10000	0	-10000	0	0
NCK2	0.019	0.002	-10000	0	-10000	0	0
p62DOK/Csk	-0.009	0.044	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SHB	0.029	0.013	-10000	0	-10000	0	0
chemotaxis	0.035	0.084	0.26	7	-0.35	3	10
STAT1-3-5/STAT1-3-5	0.042	0.022	-10000	0	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0.017	0.012	0.18	1	-10000	0	1
PTPRJ	0.019	0.003	-10000	0	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.007	0.14	-10000	0	-0.54	8	8
MAP3K8	0.016	0.011	-10000	0	-10000	0	0
FOS	-0.008	0.12	-10000	0	-0.45	11	11
PRKCA	0.016	0.012	-10000	0	-10000	0	0
PTPN7	0.012	0.068	0.26	3	-0.55	3	6
HRAS	0.017	0.009	-10000	0	-10000	0	0
PRKCB	0.011	0.064	0.26	1	-0.55	3	4
NRAS	0.017	0.008	-10000	0	-10000	0	0
RAS family/GTP	0.03	0.019	-10000	0	-10000	0	0
MAPK3	-0.005	0.12	-10000	0	-0.53	10	10
MAP2K1	-0.008	0.078	-10000	0	-0.38	7	7
ELK1	0.016	0.021	0.25	1	-10000	0	1
BRAF	-0.003	0.068	-10000	0	-0.48	4	4
mol:GTP	0	0.001	-10000	0	-0.005	16	16
MAPK1	-0.003	0.11	-10000	0	-0.56	7	7
RAF1	0	0.053	-10000	0	-0.38	4	4
KRAS	0.017	0.008	-10000	0	-10000	0	0

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.019	0.003	-10000	0	-10000	0	0
mol:PIP3	-0.016	0.044	-10000	0	-0.21	2	2
FRAP1	-0.007	0.09	-10000	0	-0.4	11	11
AKT1	-0.004	0.059	-10000	0	-0.26	1	1
INSR	0.018	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.022	0.007	-10000	0	-10000	0	0
mol:GTP	-0.006	0.059	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.016	0.027	-10000	0	-0.2	1	1
TSC2	0.019	0.003	-10000	0	-10000	0	0
RHEB/GDP	-0.022	0.03	-10000	0	-10000	0	0
TSC1	0.019	0.004	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.004	0.054	-10000	0	-0.2	15	15
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.009	0.042	-10000	0	-0.22	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.018	0.005	-10000	0	-10000	0	0
RPS6KB1	0.007	0.063	-10000	0	-0.3	2	2
MAP3K5	0.011	0.058	0.19	18	-0.21	5	23
PIK3R1	0.02	0.015	0.26	1	-10000	0	1
apoptosis	0.011	0.058	0.19	18	-0.21	5	23
mol:LY294002	0	0	-10000	0	-0.001	13	13
EIF4B	0.005	0.06	-10000	0	-0.27	2	2
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.016	0.055	-10000	0	-0.28	1	1
eIF4E/eIF4G1/eIF4A1	-0.002	0.058	-10000	0	-0.26	11	11
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.016	0.056	0.23	1	-0.19	15	16
mTOR/RHEB/GTP/Raptor/GBL	0	0.04	-10000	0	-0.2	1	1
FKBP1A	0.019	0.005	-10000	0	-10000	0	0
RHEB/GTP	-0.009	0.052	-10000	0	-10000	0	0
mol:Amino Acids	0	0	-10000	0	-0.001	13	13
FKBP12/Rapamycin	0.014	0.004	-10000	0	-10000	0	0
PDPK1	-0.02	0.041	-10000	0	-0.22	1	1
EIF4E	0.019	0.002	-10000	0	-10000	0	0
ASK1/PP5C	0.001	0.12	-10000	0	-0.51	10	10
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0	0.048	-10000	0	-10000	0	0
TSC1/TSC2	-0.004	0.065	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	0.001	13	-10000	0	13
RPS6	0.018	0.005	-10000	0	-10000	0	0
PPP5C	0.018	0.005	-10000	0	-10000	0	0
EIF4G1	0.019	0.003	-10000	0	-10000	0	0
IRS1	-0.007	0.054	-10000	0	-0.22	15	15
INS	-0.016	0.003	-10000	0	-10000	0	0
PTEN	0.017	0.006	-10000	0	-10000	0	0
PDK2	-0.02	0.041	-10000	0	-0.22	1	1
EIF4EBP1	0	0.13	-10000	0	-1	4	4
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
PPP2R5D	-0.004	0.09	0.22	1	-0.37	11	12
peptide biosynthetic process	-0.015	0.005	-10000	0	-10000	0	0
RHEB	0.018	0.005	-10000	0	-10000	0	0
EIF4A1	0.018	0.005	-10000	0	-10000	0	0
mol:Rapamycin	0	0.001	0.002	1	-10000	0	1
EEF2	-0.015	0.005	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.01	0.12	-10000	0	-0.95	4	4

×

Signaling events mediated by HDAC Class III

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
EP300	0.019	0.004	-10000	0	-10000	0	0
HDAC4	0.017	0.007	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.013	0.005	-10000	0	-10000	0	0
CDKN1A	-0.009	0.005	-10000	0	-10000	0	0
KAT2B	0.019	0.004	-10000	0	-10000	0	0
BAX	0.019	0.004	-10000	0	-10000	0	0
FOXO3	-0.002	0.005	-10000	0	-10000	0	0
FOXO1	0.017	0.007	-10000	0	-10000	0	0
FOXO4	0.006	0.002	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.019	0.004	-10000	0	-10000	0	0
TAT	-0.001	0.023	0.25	1	-10000	0	1
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.012	0.066	0.16	40	-10000	0	40
PPARGC1A	-0.09	0.22	0.25	1	-0.55	49	50
FHL2	0.02	0.015	0.25	1	-10000	0	1
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.025	0.009	-10000	0	-10000	0	0
HIST2H4A	-0.013	0.005	-10000	0	-10000	0	0
SIRT1/FOXO3a	0.013	0.028	-10000	0	-0.2	3	3
SIRT1	0.017	0.005	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.03	0.016	-10000	0	-10000	0	0
SIRT1/Histone H1b	0.019	0.041	-10000	0	-0.23	2	2
apoptosis	-0.033	0.014	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.049	0.15	-10000	0	-0.35	49	49
p53/SIRT1	0.02	0.011	-10000	0	-10000	0	0
SIRT1/FOXO4	0.016	0.035	-10000	0	-0.32	1	1
FOXO1/FHL2/SIRT1	0.031	0.016	-10000	0	-10000	0	0
HIST1H1E	0.012	0.027	0.22	1	-10000	0	1
SIRT1/p300	0.025	0.009	-10000	0	-10000	0	0
muscle cell differentiation	-0.031	0.032	-10000	0	-10000	0	0
TP53	0.015	0.007	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0.033	0.014	-10000	0	-10000	0	0
CREBBP	0.019	0.003	-10000	0	-10000	0	0
MEF2D	0.018	0.004	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.024	0.014	-10000	0	-10000	0	0
ACSS2	-0.014	0.005	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	0.031	0.032	-10000	0	-10000	0	0

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.01	0.071	-10000	0	-0.55	4	4
positive regulation of NF-kappaB transcription factor activity	0.005	0.11	-10000	0	-0.44	13	13
MAP2K4	0.006	0.072	-10000	0	-0.42	2	2
IKBKB	0.019	0.004	-10000	0	-10000	0	0
TNFRSF10B	0.019	0.004	-10000	0	-10000	0	0
TNFRSF10A	0.019	0.004	-10000	0	-10000	0	0
SMPD1	0.002	0.029	-10000	0	-0.22	4	4
IKBKG	0.019	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	-0.002	0.11	0.25	2	-0.55	10	12
TRAIL/TRAILR2	0.02	0.056	-10000	0	-0.36	5	5
TRAIL/TRAILR3	0.015	0.082	-10000	0	-0.47	6	6
TRAIL/TRAILR1	0.02	0.056	-10000	0	-0.41	4	4
TRAIL/TRAILR4	0.005	0.11	-10000	0	-0.44	13	13
TRAIL/TRAILR1/DAP3/GTP	0.029	0.038	-10000	0	-0.32	2	2
IKK complex	-0.008	0.065	-10000	0	-0.44	1	1
RIPK1	0.018	0.005	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.014	0.004	-10000	0	-10000	0	0
MAPK3	-0.02	0.048	-10000	0	-0.4	4	4
MAP3K1	-0.007	0.073	-10000	0	-0.3	12	12
TRAILR4 (trimer)	-0.002	0.11	0.25	2	-0.55	10	12
TRADD	0.018	0.005	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.019	0.004	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.007	0.06	-10000	0	-0.35	3	3
CFLAR	0.019	0.003	-10000	0	-10000	0	0
MAPK1	-0.018	0.043	-10000	0	-0.41	3	3
TRAIL/TRAILR1/FADD/TRADD/RIP	0.041	0.048	-10000	0	-0.31	3	3
mol:ceramide	0.002	0.029	-10000	0	-0.22	4	4
FADD	0.019	0.003	-10000	0	-10000	0	0
MAPK8	0.005	0.08	0.26	1	-0.4	2	3
TRAF2	0.018	0.004	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.012	0.061	-10000	0	-0.55	3	3
CHUK	0.018	0.005	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	0.03	0.05	-10000	0	-0.35	4	4
DAP3	0.018	0.005	-10000	0	-10000	0	0
CASP10	-0.008	0.055	0.22	5	-0.36	2	7
JNK cascade	0.005	0.11	-10000	0	-0.44	13	13
TRAIL (trimer)	0.01	0.071	-10000	0	-0.55	4	4
TNFRSF10C	0.012	0.061	-10000	0	-0.55	3	3
TRAIL/TRAILR1/DAP3/GTP/FADD	0.035	0.039	-10000	0	-0.31	2	2
TRAIL/TRAILR2/FADD	0.03	0.05	-10000	0	-0.35	4	4
cell death	0.002	0.029	-10000	0	-0.21	4	4
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.007	0.06	-10000	0	-0.34	3	3
TRAILR2 (trimer)	0.019	0.004	-10000	0	-10000	0	0
CASP8	0	0.074	-10000	0	-0.58	3	3
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.041	0.048	-10000	0	-0.31	3	3

×

Retinoic acid receptors-mediated signaling

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	0.019	0.004	-10000	0	-10000	0	0
HDAC3	0.019	0.003	-10000	0	-10000	0	0
VDR	-0.022	0.14	-10000	0	-0.55	18	18
Cbp/p300/PCAF	0.036	0.012	-10000	0	-10000	0	0
EP300	0.019	0.004	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	-0.002	0.068	-10000	0	-0.34	5	5
KAT2B	0.019	0.004	-10000	0	-10000	0	0
MAPK14	0.018	0.005	-10000	0	-10000	0	0
AKT1	0.009	0.073	0.23	12	-0.25	3	15
RAR alpha/9cRA/Cyclin H	0.021	0.072	-10000	0	-0.42	2	2
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0	0.059	-10000	0	-0.31	3	3
CDC2	0	0.001	-10000	0	-10000	0	0
response to UV	0	0.001	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.015	0.049	-10000	0	-0.37	3	3
NCOR2	0.019	0.004	-10000	0	-10000	0	0
VDR/VDR/Vit D3	-0.016	0.11	-10000	0	-0.4	18	18
RXRs/RARs/NRIP1/9cRA	0.008	0.1	-10000	0	-0.71	2	2
NCOA2	0.021	0.066	0.25	8	-0.55	2	10
NCOA3	0.018	0.004	-10000	0	-10000	0	0
NCOA1	0.019	0.004	-10000	0	-10000	0	0
VDR/VDR/DNA	-0.022	0.14	-10000	0	-0.55	18	18
RARG	0.02	0.015	0.26	1	-10000	0	1
RAR gamma1/9cRA	0.025	0.012	0.17	1	-10000	0	1
MAPK3	0.019	0.004	-10000	0	-10000	0	0
MAPK1	0.018	0.005	-10000	0	-10000	0	0
MAPK8	0.016	0.036	-10000	0	-0.55	1	1
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.006	0.11	-10000	0	-0.57	4	4
RARA	0.012	0.029	0.2	1	-0.26	1	2
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.001	0.061	-10000	0	-0.38	2	2
PRKCA	0.019	0.006	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	0.009	0.11	0.37	1	-0.77	2	3
RXRG	0.015	0.085	0.24	4	-0.33	10	14
RXRA	0.006	0.029	0.18	1	-0.24	2	3
RXRB	0.016	0.031	0.24	2	-10000	0	2
VDR/Vit D3/DNA	-0.016	0.11	-10000	0	-0.4	18	18
RBP1	-0.016	0.14	0.25	1	-0.55	16	17
CRBP1/9-cic-RA	-0.011	0.1	0.18	1	-0.4	16	17
RARB	0.01	0.071	-10000	0	-0.55	4	4
PRKCG	0.032	0.054	0.26	14	-10000	0	14
MNAT1	0.019	0.004	-10000	0	-10000	0	0
RAR alpha/RXRs	0.006	0.1	0.33	4	-0.53	4	8
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.009	0.091	-10000	0	-0.54	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.003	0.079	-10000	0	-0.4	3	3
RXRs/RARs/NRIP1/9cRA/HDAC3	0.009	0.11	0.32	1	-0.77	2	3
positive regulation of DNA binding	0.013	0.064	-10000	0	-0.39	2	2
NRIP1	0.01	0.12	-10000	0	-0.95	2	2
RXRs/RARs	0.009	0.097	-10000	0	-0.67	2	2
RXRs/RXRs/DNA/9cRA	-0.001	0.075	-10000	0	-0.5	2	2
PRKACA	0.018	0.005	-10000	0	-10000	0	0
CDK7	0.019	0.002	-10000	0	-10000	0	0
TFIIH	0.038	0.009	-10000	0	-10000	0	0
RAR alpha/9cRA	0.03	0.055	-10000	0	-0.3	2	2
CCNH	0.019	0.002	-10000	0	-10000	0	0
CREBBP	0.019	0.003	-10000	0	-10000	0	0
RAR gamma2/9cRA	0.031	0.018	-10000	0	-10000	0	0

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.015	0.044	-10000	0	-10000	0	0
DAPP1	0.026	0.092	0.25	6	-0.43	4	10
Src family/SYK family/BLNK-LAT/BTK-ITK	0.037	0.14	0.32	6	-0.56	6	12
mol:DAG	0.029	0.08	0.2	17	-0.25	3	20
HRAS	0.02	0.006	-10000	0	-10000	0	0
RAP1A	0.02	0.005	-10000	0	-10000	0	0
ARF5/GDP	0.02	0.06	-10000	0	-0.27	2	2
PLCG2	0.018	0.005	-10000	0	-10000	0	0
PLCG1	0.018	0.004	-10000	0	-10000	0	0
ARF5	0.018	0.004	-10000	0	-10000	0	0
mol:GTP	-0.018	0.03	-10000	0	-10000	0	0
ARF1/GTP	-0.012	0.033	0.23	1	-10000	0	1
RHOA	0.019	0.004	-10000	0	-10000	0	0
YES1	0.018	0.005	-10000	0	-10000	0	0
RAP1A/GTP	-0.017	0.032	-10000	0	-10000	0	0
ADAP1	-0.023	0.046	-10000	0	-0.3	4	4
ARAP3	-0.018	0.029	-10000	0	-10000	0	0
INPPL1	0.019	0.004	-10000	0	-10000	0	0
PREX1	0.019	0.015	0.25	1	-10000	0	1
ARHGEF6	0.019	0.003	-10000	0	-10000	0	0
ARHGEF7	0.017	0.006	-10000	0	-10000	0	0
ARF1	0.019	0.004	-10000	0	-10000	0	0
NRAS	0.02	0.006	-10000	0	-10000	0	0
FYN	0.018	0.005	-10000	0	-10000	0	0
ARF6	0.018	0.004	-10000	0	-10000	0	0
FGR	0.019	0.004	-10000	0	-10000	0	0
mol:Ca2+	0.021	0.055	0.18	10	-10000	0	10
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.024	0.036	0.25	6	-10000	0	6
ZAP70	0.052	0.082	0.25	36	-10000	0	36
mol:IP3	0.024	0.068	0.19	15	-0.18	3	18
LYN	0.018	0.005	-10000	0	-10000	0	0
ARF1/GDP	0.024	0.06	-10000	0	-0.26	3	3
RhoA/GDP	0.002	0.053	0.26	1	-10000	0	1
PDK1/Src/Hsp90	0.036	0.012	-10000	0	-10000	0	0
BLNK	0.013	0.05	-10000	0	-0.55	2	2
actin cytoskeleton reorganization	0.016	0.077	0.26	7	-0.34	2	9
SRC	0.019	0.004	-10000	0	-10000	0	0
PLEKHA2	-0.013	0.015	-10000	0	-10000	0	0
RAC1	0.018	0.006	-10000	0	-10000	0	0
PTEN	0.017	0.011	-10000	0	-10000	0	0
HSP90AA1	0.019	0.004	-10000	0	-10000	0	0
ARF6/GTP	-0.022	0.031	-10000	0	-10000	0	0
RhoA/GTP	-0.019	0.031	-10000	0	-10000	0	0
Src family/SYK family/BLNK-LAT	0.019	0.11	0.25	9	-0.51	4	13
BLK	0.036	0.076	0.25	27	-10000	0	27
PDPK1	0.019	0.002	-10000	0	-10000	0	0
CYTH1	-0.018	0.035	-10000	0	-10000	0	0
HCK	0.03	0.05	0.25	12	-10000	0	12
CYTH3	-0.018	0.031	-10000	0	-10000	0	0
CYTH2	-0.018	0.035	-10000	0	-10000	0	0
KRAS	0.02	0.006	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0	0.037	-10000	0	-10000	0	0
SGK1	0.004	0.044	-10000	0	-10000	0	0
INPP5D	0.021	0.03	0.25	4	-10000	0	4
mol:GDP	0.014	0.062	0.19	1	-0.26	3	4
SOS1	0.019	0.004	-10000	0	-10000	0	0
SYK	0.014	0.05	-10000	0	-0.55	2	2
ARF6/GDP	-0.002	0.048	0.26	1	-10000	0	1
mol:PI-3-4-5-P3	-0.016	0.035	-10000	0	-10000	0	0
ARAP3/RAP1A/GTP	-0.017	0.032	-10000	0	-10000	0	0
VAV1	0.032	0.069	0.25	17	-0.55	1	18
mol:PI-3-4-P2	-0.01	0.02	-10000	0	-10000	0	0
RAS family/GTP/PI3K Class I	-0.003	0.061	0.19	1	-10000	0	1
PLEKHA1	-0.013	0.015	-10000	0	-10000	0	0
Rac1/GDP	0.019	0.058	-10000	0	-0.27	2	2
LAT	0.027	0.044	0.25	9	-10000	0	9
Rac1/GTP	0.012	0.055	-10000	0	-0.34	1	1
ITK	-0.01	0.042	0.2	1	-10000	0	1
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.03	0.096	0.24	14	-0.35	3	17
LCK	0.042	0.083	0.25	28	-0.55	1	29
BTK	-0.017	0.036	-10000	0	-10000	0	0

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.019	0.002	-10000	0	-10000	0	0
PTK2	0.018	0.005	-10000	0	-10000	0	0
CRKL	-0.01	0.052	0.15	3	-0.38	3	6
GRB2/SOS1/SHC	0.035	0.013	-10000	0	-10000	0	0
HRAS	0.019	0.004	-10000	0	-10000	0	0
IRS1/Crk	0.009	0.049	0.18	1	-0.38	3	4
IGF-1R heterotetramer/IGF1/PTP1B	0.032	0.063	-10000	0	-0.43	3	3
AKT1	-0.009	0.063	0.22	4	-0.34	3	7
BAD	-0.012	0.06	0.21	4	-0.36	2	6
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.009	0.051	0.15	3	-0.38	3	6
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.017	0.057	0.2	4	-0.38	3	7
RAF1	-0.002	0.089	-10000	0	-0.57	3	3
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.036	0.058	-10000	0	-0.37	3	3
YWHAZ	0.018	0.005	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.019	0.057	0.2	1	-0.41	3	4
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
RPS6KB1	-0.008	0.065	0.22	4	-0.34	3	7
GNB2L1	0.018	0.004	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	0.005	0.083	0.26	1	-0.45	3	4
PXN	0.019	0.004	-10000	0	-10000	0	0
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.027	0.007	-10000	0	-10000	0	0
HRAS/GTP	0.013	0.046	-10000	0	-0.35	3	3
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.043	0.059	-10000	0	-0.36	3	3
IGF-1R heterotetramer	0.017	0.056	-10000	0	-0.6	2	2
IGF-1R heterotetramer/IGF1/IRS/Nck	0.029	0.058	-10000	0	-0.38	3	3
Crk/p130 Cas/Paxillin	0.036	0.059	-10000	0	-0.36	3	3
IGF1R	0.017	0.057	-10000	0	-0.6	2	2
IGF1	0.022	0.077	0.25	8	-0.57	3	11
IRS2/Crk	-0.01	0.047	-10000	0	-0.41	2	2
PI3K	0.037	0.06	0.29	1	-0.36	3	4
apoptosis	0.004	0.067	0.4	1	-0.24	4	5
HRAS/GDP	0.014	0.003	-10000	0	-10000	0	0
PRKCD	-0.004	0.073	-10000	0	-0.42	5	5
RAF1/14-3-3 E	0.005	0.083	0.26	1	-0.48	3	4
BAD/14-3-3	-0.004	0.07	0.25	4	-0.43	1	5
PRKCZ	-0.026	0.094	0.22	4	-0.31	16	20
Crk/p130 Cas/Paxillin/FAK1	-0.022	0.05	-10000	0	-0.44	1	1
PTPN1	0.018	0.004	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.001	0.072	-10000	0	-0.43	5	5
BCAR1	0.018	0.005	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.038	0.058	-10000	0	-0.39	3	3
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.019	0.004	-10000	0	-10000	0	0
IRS1/NCK2	0.023	0.057	-10000	0	-0.38	3	3
GRB10	0.018	0.005	-10000	0	-10000	0	0
PTPN11	-0.011	0.051	0.15	2	-0.38	3	5
IRS1	-0.003	0.062	0.18	2	-0.4	3	5
IRS2	-0.009	0.048	-10000	0	-0.42	2	2
IGF-1R heterotetramer/IGF1	0.025	0.073	-10000	0	-0.53	3	3
GRB2	0.019	0.003	-10000	0	-10000	0	0
PDPK1	-0.005	0.067	0.22	5	-0.35	3	8
YWHAE	0.018	0.005	-10000	0	-10000	0	0
PRKD1	-0.003	0.072	-10000	0	-0.42	5	5
SHC1	0.018	0.004	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.046	0.028	-10000	0	-10000	0	0
HDAC3	0.019	0.003	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.015	0.008	-10000	0	-10000	0	0
GATA1/HDAC4	-0.049	0.16	-10000	0	-0.4	44	44
GATA1/HDAC5	-0.046	0.16	-10000	0	-0.41	43	43
GATA2/HDAC5	0.026	0.041	-10000	0	-0.41	2	2
HDAC5/BCL6/BCoR	0.036	0.015	-10000	0	-10000	0	0
HDAC9	0.018	0.016	0.25	1	-10000	0	1
Glucocorticoid receptor/Hsp90/HDAC6	0.035	0.012	-10000	0	-10000	0	0
HDAC4/ANKRA2	0.024	0.016	-10000	0	-0.17	1	1
HDAC5/YWHAB	0.028	0.006	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.003	0.023	-10000	0	-0.18	4	4
GATA2	0.017	0.054	0.25	2	-0.55	2	4
HDAC4/RFXANK	0.024	0.016	-10000	0	-10000	0	0
BCOR	0.019	0.016	0.25	1	-10000	0	1
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.018	0.004	-10000	0	-10000	0	0
HDAC5	0.019	0.002	-10000	0	-10000	0	0
GNB1/GNG2	0.029	0.027	-10000	0	-10000	0	0
Histones	-0.001	0.058	-10000	0	-0.29	2	2
ADRBK1	0.019	0.003	-10000	0	-10000	0	0
HDAC4	0.017	0.007	-10000	0	-10000	0	0
XPO1	0.019	0.003	-10000	0	-10000	0	0
HDAC5/ANKRA2	0.029	0.004	-10000	0	-10000	0	0
HDAC4/Ubc9	0.024	0.016	-10000	0	-0.17	1	1
HDAC7	0.018	0.005	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.027	0.008	-10000	0	-10000	0	0
TUBA1B	0.019	0.004	-10000	0	-10000	0	0
HDAC6	0.019	0.004	-10000	0	-10000	0	0
HDAC5/RFXANK	0.028	0.005	-10000	0	-10000	0	0
CAMK4	0.034	0.059	0.25	17	-10000	0	17
Tubulin/HDAC6	0.034	0.013	-10000	0	-10000	0	0
SUMO1	0.019	0.003	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.019	0.004	-10000	0	-10000	0	0
GATA1	-0.089	0.21	0.25	1	-0.55	43	44
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.018	0.005	-10000	0	-10000	0	0
NR3C1	0.019	0.003	-10000	0	-10000	0	0
SUMO1/HDAC4	0.021	0.035	-10000	0	-0.2	1	1
SRF	0.018	0.005	-10000	0	-10000	0	0
HDAC4/YWHAB	0.024	0.016	-10000	0	-0.17	1	1
Tubulin	0.026	0.008	-10000	0	-10000	0	0
HDAC4/14-3-3 E	0.022	0.017	-10000	0	-10000	0	0
GNB1	0.018	0.006	-10000	0	-10000	0	0
RANGAP1	0.019	0.004	-10000	0	-10000	0	0
BCL6/BCoR	0.027	0.013	-10000	0	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0.032	0.019	-10000	0	-10000	0	0
HDAC4/SRF	0.039	0.041	-10000	0	-10000	0	0
HDAC4/ER alpha	0.02	0.074	-10000	0	-0.4	6	6
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	-0.001	0.057	-10000	0	-0.29	2	2
cell motility	0.034	0.013	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.019	0.002	-10000	0	-10000	0	0
HDAC7/HDAC3	0.026	0.009	-10000	0	-10000	0	0
BCL6	0.019	0.003	-10000	0	-10000	0	0
HDAC4/CaMK II delta B	0.017	0.007	-10000	0	-10000	0	0
Hsp90/HDAC6	0.026	0.008	-10000	0	-10000	0	0
ESR1	0.02	0.11	0.25	17	-0.55	6	23
HDAC6/HDAC11	0.026	0.008	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.023	0.032	-10000	0	-10000	0	0
NPC	0.011	0.001	-10000	0	-10000	0	0
MEF2C	0.019	0.002	-10000	0	-10000	0	0
RAN	0.019	0.003	-10000	0	-10000	0	0
HDAC4/MEF2C	0.045	0.028	-10000	0	-10000	0	0
GNG2	0.024	0.036	0.25	6	-10000	0	6
NCOR2	0.019	0.004	-10000	0	-10000	0	0
TUBB2A	0.018	0.005	-10000	0	-10000	0	0
HDAC11	0.018	0.004	-10000	0	-10000	0	0
HSP90AA1	0.019	0.004	-10000	0	-10000	0	0
RANBP2	0.019	0.002	-10000	0	-10000	0	0
ANKRA2	0.019	0.002	-10000	0	-10000	0	0
RFXANK	0.019	0.003	-10000	0	-10000	0	0
nuclear import	-0.016	0.016	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	0.037	0.055	-10000	0	-0.28	1	1
Ran/GTP/Exportin 1/HDAC1	-0.015	0.004	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.015	0.059	-10000	0	-0.38	1	1
SUMO1	0.019	0.003	-10000	0	-10000	0	0
ZFPM1	0.019	0.016	0.25	1	-10000	0	1
NPC/RanGAP1/SUMO1/Ubc9	0.003	0.023	-10000	0	-0.18	4	4
FKBP3	0.019	0.004	-10000	0	-10000	0	0
Histones	0.04	0.034	-10000	0	-10000	0	0
YY1/LSF	0.014	0.043	-10000	0	-10000	0	0
SMG5	0.019	0.004	-10000	0	-10000	0	0
RAN	0.019	0.003	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	0.01	0.026	-10000	0	-10000	0	0
I kappa B alpha/HDAC1	0.019	0.035	-10000	0	-10000	0	0
SAP18	0.018	0.006	-10000	0	-10000	0	0
RELA	0.012	0.03	-10000	0	-10000	0	0
HDAC1/Smad7	0.036	0.012	-10000	0	-10000	0	0
RANGAP1	0.019	0.004	-10000	0	-10000	0	0
HDAC3/TR2	0.02	0.028	-10000	0	-10000	0	0
NuRD/MBD3 Complex	0	0.042	-10000	0	-0.31	3	3
NF kappa B1 p50/RelA	0.018	0.063	0.22	1	-0.41	1	2
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	0.017	0.054	0.25	2	-0.55	2	4
GATA1	-0.089	0.21	0.25	1	-0.55	43	44
Mad/Max	0.027	0.007	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	-0.036	0.097	-10000	0	-0.35	9	9
RBBP7	0.018	0.005	-10000	0	-10000	0	0
NPC	0.011	0.001	-10000	0	-10000	0	0
RBBP4	0.019	0.003	-10000	0	-10000	0	0
MAX	0.019	0.004	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.019	0.004	-10000	0	-10000	0	0
NFKBIA	0.012	0.013	-10000	0	-10000	0	0
KAT2B	0.019	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	-0.001	0.039	-10000	0	-0.28	2	2
SIN3 complex	0.04	0.02	-10000	0	-10000	0	0
SMURF1	0.018	0.004	-10000	0	-10000	0	0
CHD3	0.018	0.006	-10000	0	-10000	0	0
SAP30	0.019	0.004	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.017	0.007	-10000	0	-10000	0	0
YY1/HDAC3	0.011	0.037	-10000	0	-10000	0	0
YY1/HDAC2	0.014	0.043	-10000	0	-10000	0	0
YY1/HDAC1	0.014	0.044	-10000	0	-10000	0	0
NuRD/MBD2 Complex (MeCP1)	0.001	0.045	-10000	0	-0.39	2	2
PPARG	0.012	0.033	-10000	0	-10000	0	0
HDAC8/hEST1B	0.035	0.013	-10000	0	-10000	0	0
UBE2I	0.019	0.002	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.019	0.004	-10000	0	-10000	0	0
TNFRSF1A	0.018	0.005	-10000	0	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.02	0.029	-10000	0	-10000	0	0
MBD3L2	-0.016	0.004	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.035	0.012	-10000	0	-10000	0	0
CREBBP	0.019	0.003	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.01	0.05	-10000	0	-0.34	1	1
HDAC1	0.019	0.004	-10000	0	-10000	0	0
HDAC3	0.013	0.013	-10000	0	-10000	0	0
HDAC2	0.018	0.005	-10000	0	-10000	0	0
YY1	0.007	0.003	-10000	0	-10000	0	0
HDAC8	0.019	0.004	-10000	0	-10000	0	0
SMAD7	0.019	0.003	-10000	0	-10000	0	0
NCOR2	0.019	0.004	-10000	0	-10000	0	0
MXD1	0.019	0.004	-10000	0	-10000	0	0
STAT3	0.01	0.003	-10000	0	-10000	0	0
NFKB1	0.019	0.001	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.019	0.002	-10000	0	-10000	0	0
YY1/LSF/HDAC1	0.023	0.044	-10000	0	-10000	0	0
YY1/SAP30/HDAC1	0.023	0.043	-10000	0	-10000	0	0
EP300	0.019	0.004	-10000	0	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.01	0.003	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.012	0.013	-10000	0	-10000	0	0
histone deacetylation	0.001	0.044	-10000	0	-0.38	2	2
STAT3 (dimer non-phopshorylated)/HDAC3	0.011	0.026	-10000	0	-10000	0	0
nuclear export	-0.035	0.013	-10000	0	-10000	0	0
PRKACA	0.018	0.005	-10000	0	-10000	0	0
GATAD2B	0.018	0.005	-10000	0	-10000	0	0
GATAD2A	0.019	0.004	-10000	0	-10000	0	0
GATA2/HDAC3	0.019	0.043	-10000	0	-0.31	2	2
GATA1/HDAC1	-0.046	0.16	-10000	0	-0.41	42	42
GATA1/HDAC3	-0.032	0.12	-10000	0	-0.31	37	37
CHD4	0.018	0.005	-10000	0	-10000	0	0
TNF-alpha/TNFR1A	0.031	0.032	-10000	0	-10000	0	0
SIN3/HDAC complex/Mad/Max	0.001	0.039	-10000	0	-0.28	3	3
NuRD Complex	0.01	0.053	-10000	0	-0.44	1	1
positive regulation of chromatin silencing	0.038	0.033	-10000	0	-10000	0	0
SIN3B	0.019	0.004	-10000	0	-10000	0	0
MTA2	0.019	0.002	-10000	0	-10000	0	0
SIN3A	0.019	0.004	-10000	0	-10000	0	0
XPO1	0.019	0.003	-10000	0	-10000	0	0
SUMO1/HDAC1	0.023	0.033	-10000	0	-10000	0	0
HDAC complex	0.043	0.018	-10000	0	-10000	0	0
GATA1/Fog1	-0.047	0.16	0.19	1	-0.41	43	44
FKBP25/HDAC1/HDAC2	0.035	0.013	-10000	0	-10000	0	0
TNF	0.025	0.045	0.25	9	-10000	0	9
negative regulation of cell growth	-0.004	0.058	-10000	0	-0.34	6	6
NuRD/MBD2/PRMT5 Complex	0.001	0.045	-10000	0	-0.39	2	2
Ran/GTP/Exportin 1	0.023	0.032	-10000	0	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.004	0.052	-10000	0	-0.39	1	1
SIN3/HDAC complex/NCoR1	0.015	0.038	-10000	0	-0.28	1	1
TFCP2	0.018	0.004	-10000	0	-10000	0	0
NR2C1	0.018	0.005	-10000	0	-10000	0	0
MBD3	0.018	0.005	-10000	0	-10000	0	0
MBD2	0.019	0.004	-10000	0	-10000	0	0

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0.02	0.071	-10000	0	-0.3	10	10
MAPK9	0.003	0.001	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.009	0.002	-10000	0	-10000	0	0
GNB1/GNG2	0.027	0.024	-10000	0	-10000	0	0
GNB1	0.018	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	0.003	0.001	-10000	0	-10000	0	0
Gs family/GTP	0	0.065	0.15	3	-0.29	11	14
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	0.005	0.016	0.077	11	-10000	0	11
GNAL	-0.001	0.11	0.25	3	-0.55	10	13
GNG2	0.024	0.036	0.25	6	-10000	0	6
CRH	-0.016	0.004	-10000	0	-10000	0	0
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.002	0.022	-10000	0	-0.35	1	1
MAPK11	0.004	0.007	0.12	1	-10000	0	1

×

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	0.019	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.004	0.088	0.24	2	-0.42	1	3
ERC1	0.018	0.005	-10000	0	-10000	0	0
RIP2/NOD2	0.033	0.038	-10000	0	-10000	0	0
NFKBIA	-0.014	0.024	-10000	0	-10000	0	0
BIRC2	0.018	0.005	-10000	0	-10000	0	0
IKBKB	0.019	0.004	-10000	0	-10000	0	0
RIPK2	0.018	0.005	-10000	0	-10000	0	0
IKBKG	-0.009	0.098	-10000	0	-0.43	4	4
IKK complex/A20	0.016	0.12	-10000	0	-0.52	3	3
NEMO/A20/RIP2	0.018	0.005	-10000	0	-10000	0	0
XPO1	0.019	0.003	-10000	0	-10000	0	0
NEMO/ATM	0.003	0.12	-10000	0	-0.44	7	7
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.019	0.003	-10000	0	-10000	0	0
Exportin 1/RanGTP	0.025	0.006	-10000	0	-10000	0	0
IKK complex/ELKS	0.003	0.11	-10000	0	-0.5	3	3
BCL10/MALT1/TRAF6	0.035	0.012	-10000	0	-10000	0	0
NOD2	0.03	0.052	0.25	13	-10000	0	13
NFKB1	0.02	0.001	-10000	0	-10000	0	0
RELA	0.02	0.004	-10000	0	-10000	0	0
MALT1	0.019	0.004	-10000	0	-10000	0	0
cIAP1/UbcH5C	0.026	0.008	-10000	0	-10000	0	0
ATM	0.018	0.005	-10000	0	-10000	0	0
TNF/TNFR1A	0.031	0.032	-10000	0	-10000	0	0
TRAF6	0.019	0.004	-10000	0	-10000	0	0
PRKCA	0.019	0.004	-10000	0	-10000	0	0
CHUK	0.018	0.005	-10000	0	-10000	0	0
UBE2D3	0.019	0.001	-10000	0	-10000	0	0
TNF	0.025	0.045	0.25	9	-10000	0	9
NF kappa B1 p50/RelA	0.039	0.011	-10000	0	-10000	0	0
BCL10	0.019	0.004	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.014	0.024	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.019	0.004	-10000	0	-10000	0	0
TNFRSF1A	0.018	0.005	-10000	0	-10000	0	0
IKK complex	0.008	0.12	-10000	0	-0.46	5	5
CYLD	0.018	0.005	-10000	0	-10000	0	0
IKK complex/PKC alpha	0.012	0.12	-10000	0	-0.52	3	3

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.019	0.004	-10000	0	-9999	0
ITGB7	0.021	0.021	0.25	2	-9999	2
ITGA4	0.025	0.036	0.25	6	-9999	6
alpha4/beta7 Integrin	0.033	0.029	-10000	0	-9999	0
alpha4/beta1 Integrin	0.031	0.026	-10000	0	-9999	0

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.03	0.064	0.36	3	-10000	0	3
CRKL	0.008	0.064	0.28	5	-10000	0	5
mol:DAG	0.015	0.033	-10000	0	-10000	0	0
HRAS	0.011	0.087	0.32	10	-10000	0	10
MAPK8	-0.001	0.054	0.18	5	-0.33	1	6
RAP1A	0.008	0.066	0.28	5	-10000	0	5
GAB1	0.008	0.065	0.28	5	-10000	0	5
MAPK14	-0.001	0.047	0.18	4	-10000	0	4
EPO	0.019	0.029	0.25	3	-10000	0	3
PLCG1	0.016	0.034	-10000	0	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0.021	0.007	-10000	0	-10000	0	0
RAPGEF1	0.019	0.004	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.038	0.022	-10000	0	-10000	0	0
GAB1/SHC/GRB2/SOS1	-0.003	0.056	0.24	1	-10000	0	1
EPO/EPOR (dimer)	0.03	0.021	-10000	0	-10000	0	0
IRS2	0.006	0.061	0.28	4	-10000	0	4
STAT1	0.02	0.035	-10000	0	-10000	0	0
STAT5B	0.018	0.035	-10000	0	-10000	0	0
cell proliferation	0.002	0.071	0.28	9	-0.32	1	10
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.015	0.04	-10000	0	-10000	0	0
TEC	0.004	0.07	0.28	4	-0.3	3	7
SOCS3	0.019	0.004	-10000	0	-10000	0	0
STAT1 (dimer)	0.02	0.035	-10000	0	-10000	0	0
JAK2	0.021	0.018	0.25	1	-10000	0	1
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
EPO/EPOR (dimer)/JAK2	0.043	0.033	-10000	0	-10000	0	0
EPO/EPOR	0.03	0.021	-10000	0	-10000	0	0
LYN	0.019	0.005	-10000	0	-10000	0	0
TEC/VAV2	-0.005	0.058	-10000	0	-0.29	3	3
elevation of cytosolic calcium ion concentration	0.021	0.007	-10000	0	-10000	0	0
SHC1	0.018	0.004	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	0.039	0.023	-10000	0	-10000	0	0
mol:IP3	0.015	0.033	-10000	0	-10000	0	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.005	0.065	0.27	4	-10000	0	4
SH2B3	0.021	0.008	-10000	0	-10000	0	0
NFKB1	0	0.051	0.18	5	-10000	0	5
EPO/EPOR (dimer)/JAK2/SOCS3	0.011	0.02	-10000	0	-10000	0	0
PTPN6	0.009	0.061	0.29	2	-10000	0	2
TEC/VAV2/GRB2	-0.005	0.062	0.26	1	-10000	0	1
EPOR	0.021	0.007	-10000	0	-10000	0	0
INPP5D	0.021	0.03	0.25	4	-10000	0	4
mol:GDP	-0.005	0.054	-10000	0	-10000	0	0
SOS1	0.019	0.004	-10000	0	-10000	0	0
PLCG2	0.018	0.005	-10000	0	-10000	0	0
CRKL/CBL/C3G	-0.001	0.056	0.26	2	-10000	0	2
VAV2	0.006	0.062	0.28	4	-10000	0	4
CBL	0.006	0.062	0.28	4	-10000	0	4
SHC/Grb2/SOS1	0.023	0.022	-10000	0	-10000	0	0
STAT5A	0.018	0.035	-10000	0	-10000	0	0
GRB2	0.019	0.003	-10000	0	-10000	0	0
STAT5 (dimer)	0.029	0.035	-10000	0	-10000	0	0
LYN/PLCgamma2	0.026	0.009	-10000	0	-10000	0	0
PTPN11	0.018	0.004	-10000	0	-10000	0	0
BTK	0.01	0.067	0.28	5	-10000	0	5
BCL2	0.028	0.067	0.36	3	-10000	0	3

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.018	0.005	-10000	0	-10000	0	0
Rac1/GDP	0.017	0.012	-10000	0	-10000	0	0
DOCK1	0.018	0.005	-10000	0	-10000	0	0
ITGA4	0.025	0.036	0.25	6	-10000	0	6
RAC1	0.018	0.006	-10000	0	-10000	0	0
alpha4/beta7 Integrin	0.033	0.029	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.018	0.005	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.038	0.026	-10000	0	-10000	0	0
alpha4/beta7 Integrin/Paxillin	0.031	0.027	-10000	0	-10000	0	0
lamellipodium assembly	-0.004	0.063	-10000	0	-0.41	3	3
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
PI3K	0.028	0.017	-10000	0	-0.17	1	1
ARF6	0.018	0.004	-10000	0	-10000	0	0
TLN1	0.018	0.005	-10000	0	-10000	0	0
PXN	-0.014	0.004	-10000	0	-10000	0	0
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
ARF6/GTP	0.034	0.025	-10000	0	-10000	0	0
cell adhesion	0.035	0.027	-10000	0	-10000	0	0
CRKL/CBL	0.025	0.01	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.029	0.025	-10000	0	-10000	0	0
ITGB1	0.019	0.004	-10000	0	-10000	0	0
ITGB7	0.021	0.021	0.25	2	-10000	0	2
ARF6/GDP	0.017	0.013	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.013	0.091	-10000	0	-0.31	17	17
p130Cas/Crk/Dock1	0.033	0.014	-10000	0	-10000	0	0
VCAM1	-0.023	0.15	-10000	0	-0.55	19	19
alpha4/beta1 Integrin/Paxillin/Talin	0.036	0.027	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.038	0.026	-10000	0	-10000	0	0
BCAR1	0.018	0.005	-10000	0	-10000	0	0
mol:GDP	-0.037	0.025	-10000	0	-10000	0	0
CBL	0.018	0.005	-10000	0	-10000	0	0
PRKACA	0.018	0.005	-10000	0	-10000	0	0
GIT1	0.019	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.036	0.027	-10000	0	-10000	0	0
Rac1/GTP	-0.005	0.068	-10000	0	-0.45	3	3

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.027	0.008	-10000	0	-10000	0	0
FBXW11	0.019	0.004	-10000	0	-10000	0	0
NF kappa B1 p50/c-Rel	-0.016	0.005	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.023	0.059	0.23	1	-0.59	1	2
NFKBIA	0.007	0.05	0.18	1	-0.43	2	3
MAPK14	0.018	0.005	-10000	0	-10000	0	0
NF kappa B1 p105/p50	-0.016	0.005	-10000	0	-10000	0	0
ARRB2	0.006	0.002	-10000	0	-10000	0	0
REL	0.019	0.004	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	-0.016	0.005	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	-0.016	0.005	-10000	0	-10000	0	0
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
NF kappa B1 p50 dimer	-0.014	0.004	-10000	0	-10000	0	0
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
NFKB1	-0.014	0.003	-10000	0	-10000	0	0
RELA	0.019	0.003	-10000	0	-10000	0	0
positive regulation of anti-apoptosis	0.013	0.053	-10000	0	-0.41	2	2
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.021	0.063	0.22	1	-0.54	1	2
SRC	0.019	0.004	-10000	0	-10000	0	0
PI3K	0.028	0.017	-10000	0	-0.17	1	1
NF kappa B1 p50/RelA	0.013	0.054	-10000	0	-0.41	2	2
IKBKB	0.019	0.004	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.019	0.004	-10000	0	-10000	0	0
SYK	0.014	0.05	-10000	0	-0.55	2	2
I kappa B alpha/PIK3R1	0.024	0.069	0.31	2	-0.37	3	5
cell death	0.02	0.06	0.22	1	-0.51	1	2
NF kappa B1 p105/c-Rel	-0.016	0.005	-10000	0	-10000	0	0
LCK	0.042	0.083	0.25	28	-0.55	1	29
BCL3	0.018	0.004	-10000	0	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	0.02	0.06	-10000	0	-0.41	5	5
AKT1	0.01	0.094	0.33	2	-0.51	1	3
PTK2B	-0.016	0.068	-10000	0	-0.55	1	1
VEGFR2 homodimer/Frs2	0.013	0.024	-10000	0	-0.35	1	1
CAV1	0.016	0.036	-10000	0	-0.55	1	1
CALM1	0.018	0.004	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.02	0.026	-10000	0	-0.32	1	1
endothelial cell proliferation	0.015	0.1	0.33	4	-0.38	2	6
mol:Ca2+	-0.012	0.036	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.032	0.028	-10000	0	-0.3	1	1
RP11-342D11.1	-0.008	0.036	-10000	0	-10000	0	0
CDH5	0.018	0.005	-10000	0	-10000	0	0
VEGFA homodimer	0.041	0.02	-10000	0	-10000	0	0
SHC1	0.018	0.004	-10000	0	-10000	0	0
SHC2	0.02	0.021	0.25	2	-10000	0	2
HRAS/GDP	0.024	0.026	-10000	0	-10000	0	0
SH2D2A	0.04	0.068	0.25	23	-10000	0	23
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.021	0.083	-10000	0	-0.44	2	2
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.04	0.053	0.29	2	-0.32	1	3
VEGFR1 homodimer	0.017	0.006	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.04	0.031	-10000	0	-10000	0	0
GRB10	-0.012	0.036	-10000	0	-10000	0	0
PTPN11	0.018	0.004	-10000	0	-10000	0	0
GRB2	0.019	0.003	-10000	0	-10000	0	0
PAK1	0.018	0.004	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.038	0.032	-10000	0	-10000	0	0
HRAS	0.019	0.004	-10000	0	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	-0.003	0.057	-10000	0	-0.37	3	3
HIF1A	0.019	0.004	-10000	0	-10000	0	0
FRS2	0.015	0.008	-10000	0	-10000	0	0
oxygen and reactive oxygen species metabolic process	0.031	0.027	-10000	0	-0.3	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.019	0.015	0.25	1	-10000	0	1
Nck/Pak	0.027	0.007	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.026	0.025	-10000	0	-0.32	1	1
mol:GDP	0.031	0.028	-10000	0	-10000	0	0
mol:NADP	0.015	0.092	0.3	2	-0.4	3	5
eNOS/Hsp90	0.022	0.085	0.28	1	-0.38	3	4
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
mol:IP3	-0.012	0.037	-10000	0	-10000	0	0
HIF1A/ARNT	0.026	0.009	-10000	0	-10000	0	0
SHB	0.018	0.005	-10000	0	-10000	0	0
VEGFA	0.019	0.005	-10000	0	-10000	0	0
VEGFC	0.019	0.004	-10000	0	-10000	0	0
FAK1/Vinculin	0.014	0.081	0.32	2	-0.44	2	4
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.019	0.004	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.029	0.059	-10000	0	-0.36	5	5
PTPN6	0.019	0.015	0.25	1	-10000	0	1
EPAS1	0.019	0.036	-10000	0	-0.55	1	1
mol:L-citrulline	0.015	0.092	0.3	2	-0.4	3	5
ITGAV	0.019	0.003	-10000	0	-10000	0	0
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.027	0.029	-10000	0	-0.3	1	1
VEGFR2 homodimer/VEGFA homodimer	0.027	0.025	-10000	0	-0.32	1	1
VEGFR2/3 heterodimer	0.017	0.026	-10000	0	-0.35	1	1
VEGFB	0.019	0.002	-10000	0	-10000	0	0
MAPK11	0.008	0.067	0.36	1	-10000	0	1
VEGFR2 homodimer	-0.012	0.025	-10000	0	-0.4	1	1
FLT1	0.017	0.006	-10000	0	-10000	0	0
NEDD4	0.019	0.004	-10000	0	-10000	0	0
MAPK3	0.008	0.078	0.34	4	-0.39	1	5
MAPK1	0.01	0.079	0.34	4	-0.39	1	5
VEGFA145/NRP2	0.026	0.009	-10000	0	-10000	0	0
VEGFR1/2 heterodimer	0.016	0.024	-10000	0	-0.35	1	1
KDR	-0.012	0.025	-10000	0	-0.4	1	1
VEGFA165/NRP1/VEGFR2 homodimer	0.026	0.024	-10000	0	-10000	0	0
SRC	0.019	0.004	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	0.011	0.08	0.34	4	-0.39	1	5
PI3K	0.008	0.051	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.027	0.024	-10000	0	-0.32	1	1
FES	-0.012	0.039	-10000	0	-10000	0	0
GAB1	-0.004	0.054	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src	0.026	0.024	-10000	0	-0.32	1	1
CTNNB1	0.019	0.003	-10000	0	-10000	0	0
SOS1	0.019	0.004	-10000	0	-10000	0	0
ARNT	0.018	0.005	-10000	0	-10000	0	0
eNOS/Caveolin-1	0.016	0.088	0.3	2	-0.39	4	6
VEGFR2 homodimer/VEGFA homodimer/Yes	0.025	0.025	-10000	0	-0.32	1	1
PI3K/GAB1	0.006	0.075	0.3	1	-10000	0	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.031	0.033	-10000	0	-0.3	1	1
PRKACA	0.018	0.005	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.026	0.026	-10000	0	-0.32	1	1
HSP90AA1	0.019	0.004	-10000	0	-10000	0	0
CDC42	-0.012	0.039	-10000	0	-10000	0	0
actin cytoskeleton reorganization	0.039	0.053	0.29	2	-0.32	1	3
PTK2	-0.005	0.07	0.3	1	-0.46	2	3
EDG1	-0.008	0.036	-10000	0	-10000	0	0
mol:DAG	-0.012	0.037	-10000	0	-10000	0	0
CaM/Ca2+	-0.014	0.035	-10000	0	-10000	0	0
MAP2K3	-0.006	0.063	0.34	1	-10000	0	1
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.029	0.039	-10000	0	-10000	0	0
PLCG1	-0.012	0.037	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.033	0.027	-10000	0	-0.3	1	1
IQGAP1	0.019	0.004	-10000	0	-10000	0	0
YES1	0.018	0.005	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.025	0.025	-10000	0	-0.32	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.027	0.026	-10000	0	-0.32	1	1
cell migration	0.007	0.097	0.29	2	-0.44	1	3
mol:PI-3-4-5-P3	0.008	0.049	-10000	0	-10000	0	0
FYN	0.018	0.005	-10000	0	-10000	0	0
VEGFB/NRP1	-0.011	0.036	-10000	0	-10000	0	0
mol:NO	0.015	0.092	0.3	2	-0.4	3	5
PXN	0.019	0.004	-10000	0	-10000	0	0
HRAS/GTP	-0.024	0.019	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.017	0.022	-10000	0	-10000	0	0
VHL	0.018	0.004	-10000	0	-10000	0	0
ITGB3	0.008	0.079	-10000	0	-0.55	5	5
NOS3	0.015	0.099	0.31	2	-0.45	3	5
VEGFR2 homodimer/VEGFA homodimer/Sck	0.026	0.028	-10000	0	-0.32	1	1
RAC1	0.018	0.006	-10000	0	-10000	0	0
PRKCA	-0.004	0.057	0.34	1	-10000	0	1
PRKCB	-0.006	0.071	0.34	1	-0.55	1	2
VCL	0.018	0.005	-10000	0	-10000	0	0
VEGFA165/NRP1	-0.008	0.037	-10000	0	-10000	0	0
VEGFR1/2 heterodimer/VEGFA homodimer	0.025	0.025	-10000	0	-0.32	1	1
VEGFA165/NRP2	0.026	0.009	-10000	0	-10000	0	0
MAPKKK cascade	-0.017	0.045	-10000	0	-10000	0	0
NRP2	0.019	0.003	-10000	0	-10000	0	0
VEGFC homodimer	0.019	0.004	-10000	0	-10000	0	0
NCK1	0.019	0.002	-10000	0	-10000	0	0
ROCK1	0.019	0.004	-10000	0	-10000	0	0
FAK1/Paxillin	0.012	0.083	0.32	2	-0.44	2	4
MAP3K13	-0.014	0.047	-10000	0	-10000	0	0
PDPK1	-0.008	0.057	0.25	3	-10000	0	3

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.017	0.006	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP1	-0.009	0.003	-10000	0	-10000	0	0
mol:DAG	-0.01	0.029	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	0.015	0.006	-10000	0	-10000	0	0
CaM/Ca2+	-0.013	0.029	-10000	0	-10000	0	0
HIF1A	0.021	0.004	-10000	0	-10000	0	0
GAB1	0.019	0.003	-10000	0	-10000	0	0
AKT1	-0.011	0.034	-10000	0	-10000	0	0
PLCG1	-0.01	0.029	-10000	0	-10000	0	0
NOS3	-0.001	0.066	0.37	1	-0.45	2	3
CBL	0.018	0.005	-10000	0	-10000	0	0
mol:NO	0.002	0.077	0.41	2	-0.43	2	4
FLT1	-0.011	0.004	-10000	0	-10000	0	0
PGF	0.03	0.052	0.25	13	-10000	0	13
VEGFR1 homodimer/NRP2/VEGFR121	0.025	0.012	-10000	0	-10000	0	0
CALM1	0.018	0.004	-10000	0	-10000	0	0
PIK3CA	0.019	0.003	-10000	0	-10000	0	0
eNOS/Hsp90	0.014	0.074	0.36	1	-0.42	2	3
endothelial cell proliferation	0.004	0.066	0.34	2	-10000	0	2
mol:Ca2+	-0.01	0.028	-10000	0	-10000	0	0
MAPK3	-0.01	0.049	0.26	6	-10000	0	6
MAPK1	-0.01	0.049	0.26	6	-10000	0	6
PIK3R1	0.02	0.015	0.25	1	-10000	0	1
PLGF homodimer	0.03	0.052	0.25	13	-10000	0	13
PRKACA	0.018	0.005	-10000	0	-10000	0	0
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	0.016	0.036	-10000	0	-0.55	1	1
VEGFA homodimer	0.018	0.005	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0.016	0.007	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	-0.012	0.049	0.32	2	-10000	0	2
PI3K	0.041	0.038	-10000	0	-10000	0	0
PRKCA	-0.013	0.024	-10000	0	-10000	0	0
PRKCB	-0.016	0.041	-10000	0	-0.31	3	3
VEGFR1 homodimer/PLGF homodimer	0.025	0.037	-10000	0	-10000	0	0
VEGFA	0.018	0.005	-10000	0	-10000	0	0
VEGFB	0.019	0.002	-10000	0	-10000	0	0
mol:IP3	-0.01	0.029	-10000	0	-10000	0	0
RASA1	-0.014	0.025	-10000	0	-10000	0	0
NRP2	0.019	0.003	-10000	0	-10000	0	0
VEGFR1 homodimer	-0.011	0.004	-10000	0	-10000	0	0
VEGFB homodimer	0.019	0.002	-10000	0	-10000	0	0
NCK1	0.019	0.002	-10000	0	-10000	0	0
eNOS/Caveolin-1	0.011	0.076	0.36	1	-0.42	2	3
PTPN11	0.018	0.004	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.039	0.037	-10000	0	-10000	0	0
mol:L-citrulline	0.002	0.077	0.41	2	-0.43	2	4
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.032	0.019	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.025	0.012	-10000	0	-10000	0	0
CD2AP	0.018	0.005	-10000	0	-10000	0	0
PI3K/GAB1	0.045	0.039	-10000	0	-10000	0	0
PDPK1	-0.012	0.047	0.33	2	-10000	0	2
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.024	0.013	-10000	0	-10000	0	0
mol:NADP	0.002	0.077	0.41	2	-0.43	2	4
HSP90AA1	0.019	0.004	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.03	0.019	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP2	0.016	0.007	-10000	0	-10000	0	0

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.01	0.023	-10000	0	-0.29	1	1
TRAF2/ASK1	0.022	0.025	-10000	0	-0.35	1	1
ATM	0.018	0.005	-10000	0	-10000	0	0
MAP2K3	0.017	0.075	0.3	2	-0.27	1	3
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.007	0.089	0.3	5	-0.3	4	9
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.022	0.079	0.25	11	-0.55	3	14
TXN	0.003	0.001	-10000	0	-10000	0	0
CALM1	0.018	0.004	-10000	0	-10000	0	0
GADD45A	0.016	0.036	-10000	0	-0.55	1	1
GADD45B	0.019	0.003	-10000	0	-10000	0	0
MAP3K1	0.019	0.003	-10000	0	-10000	0	0
MAP3K6	0.019	0.004	-10000	0	-10000	0	0
MAP3K7	0.019	0.004	-10000	0	-10000	0	0
MAP3K4	0.018	0.004	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.024	0.029	-10000	0	-0.41	1	1
TAK1/TAB family	-0.002	0.018	-10000	0	-0.14	3	3
RAC1/OSM/MEKK3	0.033	0.013	-10000	0	-10000	0	0
TRAF2	0.018	0.004	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.021	0.056	-10000	0	-10000	0	0
TRAF6	0.003	0.001	-10000	0	-10000	0	0
RAC1	0.018	0.006	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	0.033	0.074	0.25	20	-0.55	1	21
CCM2	0.018	0.005	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	0.033	0.047	0.17	20	-0.35	1	21
MAPK11	0.019	0.015	0.25	1	-10000	0	1
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.038	0.051	-10000	0	-0.32	2	2
OSM/MEKK3	0.026	0.008	-10000	0	-10000	0	0
TAOK1	0.009	0.018	-10000	0	-10000	0	0
TAOK2	0.006	0.002	-10000	0	-10000	0	0
TAOK3	0.006	0.002	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.018	0.005	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.016	0.036	-10000	0	-0.55	1	1
MAP3K10	0.018	0.005	-10000	0	-10000	0	0
MAP3K3	0.019	0.003	-10000	0	-10000	0	0
TRX/ASK1	0.013	0.025	-10000	0	-0.33	1	1
GADD45/MTK1/MTK1	0.04	0.052	-10000	0	-0.29	4	4

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.019	0.003	-10000	0	-10000	0	0
SMAD2	-0.016	0.053	-10000	0	-0.26	2	2
SMAD3	0.022	0.059	0.26	1	-10000	0	1
SMAD3/SMAD4	0.011	0.089	-10000	0	-0.39	7	7
SMAD4/Ubc9/PIASy	0.037	0.01	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.009	0.063	-10000	0	-10000	0	0
PPM1A	0.019	0.004	-10000	0	-10000	0	0
CALM1	0.018	0.004	-10000	0	-10000	0	0
SMAD2/SMAD4	-0.007	0.055	-10000	0	-0.27	1	1
MAP3K1	0.019	0.003	-10000	0	-10000	0	0
TRAP-1/SMAD4	0.024	0.039	-10000	0	-0.41	2	2
MAPK3	0.019	0.004	-10000	0	-10000	0	0
MAPK1	0.018	0.005	-10000	0	-10000	0	0
NUP214	0.019	0.003	-10000	0	-10000	0	0
CTDSP1	0.018	0.004	-10000	0	-10000	0	0
CTDSP2	0.015	0.008	-10000	0	-10000	0	0
CTDSPL	0.019	0.003	-10000	0	-10000	0	0
KPNB1	0.019	0.002	-10000	0	-10000	0	0
TGFBRAP1	0.015	0.05	-10000	0	-0.55	2	2
UBE2I	0.019	0.002	-10000	0	-10000	0	0
NUP153	0.018	0.004	-10000	0	-10000	0	0
KPNA2	0.019	0.003	-10000	0	-10000	0	0
PIAS4	0.019	0.003	-10000	0	-10000	0	0

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.03	0.034	-10000	0	-10000	0	0
CLOCK	0.02	0.004	-10000	0	-10000	0	0
TIMELESS/CRY2	0.021	0.032	-10000	0	-10000	0	0
DEC1/BMAL1	0.032	0.029	-10000	0	-10000	0	0
ATR	0.019	0.002	-10000	0	-10000	0	0
NR1D1	0.007	0.014	-10000	0	-10000	0	0
ARNTL	0.02	0.004	-10000	0	-10000	0	0
TIMELESS	0.007	0.024	-10000	0	-10000	0	0
NPAS2	0.015	0.05	-10000	0	-0.55	2	2
CRY2	0.019	0.004	-10000	0	-10000	0	0
mol:CO	-0.004	0.007	-10000	0	-0.11	1	1
CHEK1	0.018	0.005	-10000	0	-10000	0	0
mol:HEME	0.004	0.007	0.11	1	-10000	0	1
PER1	0.018	0.006	-10000	0	-10000	0	0
BMAL/CLOCK/NPAS2	0.037	0.037	-10000	0	-0.35	2	2
BMAL1/CLOCK	0.016	0.035	-10000	0	-10000	0	0
S phase of mitotic cell cycle	0.03	0.034	-10000	0	-10000	0	0
TIMELESS/CHEK1/ATR	0.031	0.034	-10000	0	-10000	0	0
mol:NADPH	0.004	0.007	0.11	1	-10000	0	1
PER1/TIMELESS	0.02	0.034	-10000	0	-10000	0	0
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.013	0.049	0.25	9	-10000	0	9

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.019	0.004	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.016	0.009	-9999	-10000	0	0
MDM2/SUMO1	0.019	0.03	-9999	-10000	0	0
HDAC4	0.017	0.007	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	-0.016	0.008	-9999	-10000	0	0
SUMO1	0.019	0.003	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.004	0.012	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
XPO1	-0.005	0.018	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.019	0.003	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.019	0.002	-9999	-10000	0	0
SUMO1/HDAC4	0.021	0.035	-9999	-0.2	1	1
SUMO1/HDAC1	0.023	0.033	-9999	-10000	0	0
RANGAP1	0.019	0.004	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	0.035	0.023	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.003	0.023	-9999	-0.18	4	4
Ran/GTP	0.014	0.03	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.015	0.008	-9999	-10000	0	0
UBE2I	0.019	0.002	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.011	0.032	-9999	-10000	0	0
NPC	0.011	0.001	-9999	-10000	0	0
PIAS2	0.019	0.003	-9999	-10000	0	0
PIAS1	0.018	0.004	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.011	0.047	0.31	1	-10000	0	1
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.002	0.041	-10000	0	-0.2	2	2
AP2	0.027	0.007	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.021	0.014	-10000	0	-10000	0	0
CLTB	0.018	0.004	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.006	0.018	-10000	0	-0.19	2	2
CD4	0.024	0.036	0.25	6	-10000	0	6
CLTA	0.018	0.005	-10000	0	-10000	0	0
mol:GTP	-0.002	0.003	-10000	0	-10000	0	0
ARFGAP1	-0.007	0.002	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.003	0.005	-10000	0	-10000	0	0
ARF1/GTP	0.019	0.02	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	-0.004	0.014	-10000	0	-10000	0	0
mol:Choline	-0.003	0.004	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.019	0.009	-10000	0	-10000	0	0
DDEF1	-0.002	0.004	-10000	0	-10000	0	0
ARF1/GDP	0.001	0.016	-10000	0	-10000	0	0
AP2M1	0.019	0.003	-10000	0	-10000	0	0
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	-0.008	0.009	-10000	0	-10000	0	0
Rac/GTP	0.013	0.007	-10000	0	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.022	0.013	-10000	0	-10000	0	0
ARFIP2	0.013	0.015	-10000	0	-10000	0	0
COPA	0.018	0.005	-10000	0	-10000	0	0
RAC1	0.018	0.006	-10000	0	-10000	0	0
ARF1/GTP/coatomer protein complex	0.003	0.038	0.16	1	-0.23	3	4
ARF1/GTP/ARHGAP10	0.012	0.007	-10000	0	-10000	0	0
GGA3	0.019	0.004	-10000	0	-10000	0	0
ARF1/GTP/Membrin	0.014	0.014	-10000	0	-10000	0	0
AP2A1	0.019	0.003	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.002	0.02	-10000	0	-10000	0	0
ARF1/GDP/Membrin	0.017	0.016	-10000	0	-10000	0	0
Arfaptin 2/Rac/GDP	0.021	0.013	-10000	0	-10000	0	0
CYTH2	0.019	0.008	-10000	0	-10000	0	0
ARF1/GTP/GGA3	0.024	0.011	-10000	0	-10000	0	0
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.013	0.004	-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	0.005	0.047	-10000	0	-0.28	1	1
PLD2	-0.003	0.004	-10000	0	-10000	0	0
ARF-GAP1/v-SNARE	-0.007	0.002	-10000	0	-10000	0	0
PIP5K1A	-0.003	0.005	-10000	0	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0.006	0.025	-10000	0	-10000	0	0
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.003	0.004	-10000	0	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	-0.007	0.002	-10000	0	-10000	0	0
GOSR2	0.006	0.004	-10000	0	-10000	0	0
USO1	0.002	0.035	-10000	0	-0.32	3	3
GBF1	-0.003	0.054	-10000	0	-0.32	7	7
ARF1/GTP/Arfaptin 2	0.023	0.014	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.039	0.026	-10000	0	-10000	0	0

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
IKK alpha homodimer	0.027	0.008	-9999	-9999
FBXW11	0.019	0.004	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-9999
beta TrCP1/SCF ubiquitin ligase complex	0.019	0.004	-9999	-9999
CHUK	0.018	0.005	-9999	-9999
NF kappa B2 p100/RelB	0.048	0.022	-9999	-9999
NFKB1	0.019	0.001	-9999	-9999
MAP3K14	0.019	0.002	-9999	-9999
NF kappa B1 p50/RelB	0.027	0.007	-9999	-9999
RELB	0.018	0.004	-9999	-9999
NFKB2	0.018	0.005	-9999	-9999
NF kappa B2 p52/RelB	0.024	0.008	-9999	-9999
regulation of B cell activation	0.023	0.008	-9999	-9999

pid_entity	TCGA.Z4.AAPG	TCGA.Z4.AAPF	TCGA.Z4.A9VC	TCGA.Z4.A8JB
109_MAP3K5	0.0087	0.043	0.0087	0.0087
47_PPARGC1A	0.019	0.019	0.019	0.019
105_BMP4	0.019	0.019	0.019	0.019
105_BMP6	0.019	0.019	0.019	0.019
105_BMP7	0	0.25	0.019	0.019
105_BMP2	0.019	0.019	0.019	0.019
131_RELN/VLDLR	0.05	0.05	-0.32	0.05
30_TGFB1/TGF beta receptor Type II	0.019	0.019	0.019	0.019
84_STAT5B	-0.057	-0.049	0.014	-0.057
84_STAT5A	-0.057	-0.049	0.014	-0.057