PARADIGM pathway analysis of mRNASeq expression data

Pathway.Name	Avg.Num.Perturbations
FOXA2 and FOXA3 transcription factor networks	109
Nephrin/Neph1 signaling in the kidney podocyte	78
E-cadherin signaling events	67
Stabilization and expansion of the E-cadherin adherens junction	55
IL4-mediated signaling events	46
EGFR-dependent Endothelin signaling events	45
ErbB2/ErbB3 signaling events	43
Signaling events mediated by the Hedgehog family	40
Glypican 2 network	38
Signaling mediated by p38-alpha and p38-beta	37

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	0.4225	109	5022	46	-1.5	0.01	1000	-1000	-0.071	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.3023	78	2671	34	-0.37	0	1000	-1000	-0.065	-1000
E-cadherin signaling events	0.2597	67	335	5	-0.34	0	1000	-1000	-0.052	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.2132	55	4071	74	-0.35	0.19	1000	-1000	-0.087	-1000
IL4-mediated signaling events	0.1783	46	4214	91	-1.3	0.77	1000	-1000	-0.15	-1000
EGFR-dependent Endothelin signaling events	0.1744	45	952	21	-0.32	0	1000	-1000	-0.07	-1000
ErbB2/ErbB3 signaling events	0.1667	43	2841	65	-0.52	0.026	1000	-1000	-0.068	-1000
Signaling events mediated by the Hedgehog family	0.1550	40	2110	52	-0.37	0.18	1000	-1000	-0.074	-1000
Glypican 2 network	0.1473	38	155	4	-0.1	-0.095	1000	-1000	-0.032	-1000
Signaling mediated by p38-alpha and p38-beta	0.1434	37	1667	44	-0.4	0	1000	-1000	-0.065	-1000
E-cadherin signaling in the nascent adherens junction	0.1395	36	2762	76	-0.34	0	1000	-1000	-0.088	-1000
TCGA08_retinoblastoma	0.1357	35	282	8	-0.25	0.053	1000	-1000	-0.021	-1000
Wnt signaling	0.1279	33	237	7	-0.088	-0.01	1000	-1000	-0.045	-1000
Reelin signaling pathway	0.1202	31	1739	56	-0.27	0	1000	-1000	-0.095	-1000
TCGA08_p53	0.1085	28	201	7	-0.16	0.031	1000	-1000	-0.024	-1000
Signaling events regulated by Ret tyrosine kinase	0.0969	25	2119	82	-0.26	0	1000	-1000	-0.085	-1000
Syndecan-1-mediated signaling events	0.0891	23	808	34	-0.29	0	1000	-1000	-0.079	-1000
amb2 Integrin signaling	0.0891	23	1904	82	-0.3	0.004	1000	-1000	-0.081	-1000
E-cadherin signaling in keratinocytes	0.0891	23	1015	43	-0.34	0.084	1000	-1000	-0.071	-1000
Osteopontin-mediated events	0.0853	22	837	38	-0.15	0	1000	-1000	-0.098	-1000
Aurora B signaling	0.0814	21	1447	67	-0.31	0.001	1000	-1000	-0.067	-1000
Thromboxane A2 receptor signaling	0.0736	19	2039	105	-0.32	0.014	1000	-1000	-0.069	-1000
Noncanonical Wnt signaling pathway	0.0698	18	488	26	-0.088	0	1000	-1000	-0.069	-1000
Integrins in angiogenesis	0.0698	18	1527	84	-0.44	0.006	1000	-1000	-0.094	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0659	17	961	54	-0.2	0.019	1000	-1000	-0.094	-1000
Coregulation of Androgen receptor activity	0.0620	16	1264	76	-0.7	0.027	1000	-1000	-0.043	-1000
Aurora C signaling	0.0620	16	115	7	-0.13	0	1000	-1000	-0.037	-1000
BMP receptor signaling	0.0620	16	1373	81	-0.4	0.028	1000	-1000	-0.084	-1000
LPA4-mediated signaling events	0.0581	15	180	12	-0.19	0.017	1000	-1000	-0.017	-1000
TCR signaling in naïve CD8+ T cells	0.0581	15	1405	93	-0.21	0.1	1000	-1000	-0.082	-1000
IL23-mediated signaling events	0.0581	15	939	60	-0.24	0.014	1000	-1000	-0.13	-1000
Ephrin A reverse signaling	0.0543	14	101	7	-0.072	0	1000	-1000	-0.038	-1000
Arf6 signaling events	0.0543	14	925	62	-0.32	0.012	1000	-1000	-0.056	-1000
Fc-epsilon receptor I signaling in mast cells	0.0543	14	1368	97	-0.14	0.026	1000	-1000	-0.084	-1000
PDGFR-alpha signaling pathway	0.0543	14	638	44	-0.11	0.007	1000	-1000	-0.061	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0543	14	1236	88	-0.24	0.021	1000	-1000	-0.1	-1000
FOXM1 transcription factor network	0.0543	14	744	51	-0.24	0.014	1000	-1000	-0.18	-1000
p75(NTR)-mediated signaling	0.0504	13	1660	125	-0.48	0.026	1000	-1000	-0.097	-1000
Endothelins	0.0504	13	1285	96	-0.49	0.024	1000	-1000	-0.083	-1000
Syndecan-4-mediated signaling events	0.0504	13	915	67	-0.18	0.036	1000	-1000	-0.094	-1000
S1P5 pathway	0.0465	12	204	17	-0.1	0.059	1000	-1000	-0.051	-1000
Effects of Botulinum toxin	0.0465	12	327	26	-0.1	0	1000	-1000	-0.053	-1000
Visual signal transduction: Cones	0.0426	11	425	38	-0.14	0	1000	-1000	-0.066	-1000
Calcium signaling in the CD4+ TCR pathway	0.0426	11	348	31	-0.24	0	1000	-1000	-0.11	-1000
Nongenotropic Androgen signaling	0.0426	11	586	52	-0.1	0.009	1000	-1000	-0.054	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0426	11	377	33	-0.24	0	1000	-1000	-0.063	-1000
Class IB PI3K non-lipid kinase events	0.0426	11	33	3	-0.034	-1000	1000	-1000	-0.02	-1000
S1P4 pathway	0.0426	11	284	25	-0.1	0	1000	-1000	-0.054	-1000
ErbB4 signaling events	0.0388	10	713	69	-0.1	0.04	1000	-1000	-0.087	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0388	10	549	52	-0.17	0.042	1000	-1000	-0.066	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0388	10	736	68	-0.21	0.026	1000	-1000	-0.14	-1000
IL2 signaling events mediated by STAT5	0.0388	10	221	22	-0.094	0.028	1000	-1000	-0.073	-1000
HIF-1-alpha transcription factor network	0.0349	9	692	76	-0.37	0.061	1000	-1000	-0.15	-1000
Signaling events mediated by PTP1B	0.0349	9	750	76	-0.32	0.036	1000	-1000	-0.078	-1000
PLK1 signaling events	0.0349	9	779	85	-0.17	0.011	1000	-1000	-0.059	-1000
Glucocorticoid receptor regulatory network	0.0349	9	1042	114	-0.23	0.18	1000	-1000	-0.079	-1000
S1P1 pathway	0.0349	9	349	36	-0.23	0.012	1000	-1000	-0.073	-1000
LPA receptor mediated events	0.0349	9	922	102	-0.15	0.027	1000	-1000	-0.078	-1000
Insulin Pathway	0.0349	9	739	74	-0.26	0.031	1000	-1000	-0.086	-1000
Visual signal transduction: Rods	0.0349	9	499	52	-0.14	0	1000	-1000	-0.086	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0349	9	712	78	-0.087	0.037	1000	-1000	-0.13	-1000
Regulation of Androgen receptor activity	0.0349	9	650	70	-0.73	0.012	1000	-1000	-0.069	-1000
IL12-mediated signaling events	0.0310	8	778	87	-0.099	0.023	1000	-1000	-0.12	-1000
Presenilin action in Notch and Wnt signaling	0.0310	8	497	61	-0.13	0.042	1000	-1000	-0.067	-1000
Glypican 1 network	0.0310	8	425	48	-0.24	0.007	1000	-1000	-0.05	-1000
Signaling mediated by p38-gamma and p38-delta	0.0310	8	134	15	-0.14	0.02	1000	-1000	-0.059	-1000
S1P3 pathway	0.0310	8	361	42	-0.1	0.001	1000	-1000	-0.054	-1000
Regulation of nuclear SMAD2/3 signaling	0.0271	7	1043	136	-0.37	0.066	1000	-1000	-0.089	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0271	7	215	28	-0.1	0	1000	-1000	-0.055	-1000
Nectin adhesion pathway	0.0271	7	449	63	-0.34	0.034	1000	-1000	-0.072	-1000
Ephrin B reverse signaling	0.0271	7	360	48	-0.051	0.03	1000	-1000	-0.067	-1000
FoxO family signaling	0.0271	7	489	64	-0.4	0.039	1000	-1000	-0.087	-1000
Plasma membrane estrogen receptor signaling	0.0271	7	658	86	-0.12	0.03	1000	-1000	-0.08	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0271	7	869	120	-0.17	0.053	1000	-1000	-0.076	-1000
Canonical Wnt signaling pathway	0.0233	6	348	51	-0.13	0.04	1000	-1000	-0.066	-1000
Regulation of Telomerase	0.0233	6	711	102	-0.36	0.016	1000	-1000	-0.1	-1000
PLK2 and PLK4 events	0.0194	5	15	3	-0.017	0.005	1000	-1000	-0.025	-1000
Syndecan-2-mediated signaling events	0.0194	5	348	69	-0.18	0.032	1000	-1000	-0.054	-1000
Insulin-mediated glucose transport	0.0194	5	166	32	-0.16	0.019	1000	-1000	-0.06	-1000
Ceramide signaling pathway	0.0194	5	411	76	-0.32	0.1	1000	-1000	-0.059	-1000
IL2 signaling events mediated by PI3K	0.0194	5	323	58	-0.076	0.049	1000	-1000	-0.085	-1000
IL27-mediated signaling events	0.0194	5	270	51	-0.14	0.005	1000	-1000	-0.071	-1000
Arf6 trafficking events	0.0194	5	411	71	-0.36	0.08	1000	-1000	-0.071	-1000
Signaling events mediated by PRL	0.0194	5	191	34	-0.18	0.027	1000	-1000	-0.056	-1000
BARD1 signaling events	0.0155	4	228	57	-0.16	0.1	1000	-1000	-0.062	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0155	4	363	85	-0.049	0.037	1000	-1000	-0.07	-1000
IL1-mediated signaling events	0.0155	4	287	62	-0.091	0.024	1000	-1000	-0.093	-1000
FAS signaling pathway (CD95)	0.0155	4	222	47	-0.12	0.017	1000	-1000	-0.049	-1000
Retinoic acid receptors-mediated signaling	0.0155	4	246	58	-0.058	0.032	1000	-1000	-0.066	-1000
Syndecan-3-mediated signaling events	0.0155	4	140	35	-0.064	0	1000	-1000	-0.059	-1000
IL6-mediated signaling events	0.0155	4	314	75	-0.075	0.081	1000	-1000	-0.083	-1000
Ras signaling in the CD4+ TCR pathway	0.0155	4	73	17	-0.033	0.02	1000	-1000	-0.06	-1000
Caspase cascade in apoptosis	0.0116	3	234	74	-0.13	0.037	1000	-1000	-0.06	-1000
JNK signaling in the CD4+ TCR pathway	0.0116	3	60	17	-0.025	0.036	1000	-1000	-0.073	-1000
Cellular roles of Anthrax toxin	0.0116	3	137	39	-0.11	0.018	1000	-1000	-0.028	-1000
Aurora A signaling	0.0116	3	238	60	-0.16	0.016	1000	-1000	-0.064	-1000
IFN-gamma pathway	0.0116	3	215	68	-0.086	0.047	1000	-1000	-0.094	-1000
Class I PI3K signaling events mediated by Akt	0.0116	3	259	68	-0.21	0.037	1000	-1000	-0.065	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0116	3	133	37	-0.065	0	1000	-1000	-0.072	-1000
TRAIL signaling pathway	0.0116	3	184	48	-0.036	0.037	1000	-1000	-0.063	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0116	3	299	83	-0.091	0.017	1000	-1000	-0.084	-1000
EPHB forward signaling	0.0116	3	284	85	-0.14	0.045	1000	-1000	-0.089	-1000
Regulation of p38-alpha and p38-beta	0.0116	3	172	54	-0.07	0.037	1000	-1000	-0.069	-1000
BCR signaling pathway	0.0116	3	391	99	-0.068	0.037	1000	-1000	-0.086	-1000
IGF1 pathway	0.0116	3	178	57	-0.059	0.034	1000	-1000	-0.091	-1000
Rapid glucocorticoid signaling	0.0116	3	61	20	-0.041	0.006	1000	-1000	-0.036	-1000
Signaling events mediated by HDAC Class II	0.0078	2	219	75	-0.14	0.002	1000	-1000	-0.055	-1000
Hedgehog signaling events mediated by Gli proteins	0.0078	2	189	65	-0.1	0.037	1000	-1000	-0.081	-1000
Signaling events mediated by HDAC Class III	0.0078	2	111	40	-0.16	0.025	1000	-1000	-0.049	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0078	2	104	45	-0.059	0.055	1000	-1000	-0.08	-1000
TCGA08_rtk_signaling	0.0078	2	71	26	-0.075	0.032	1000	-1000	-0.03	-1000
Class I PI3K signaling events	0.0078	2	169	73	-0.046	0.043	1000	-1000	-0.072	-1000
PDGFR-beta signaling pathway	0.0078	2	252	97	-0.14	0.05	1000	-1000	-0.085	-1000
a4b1 and a4b7 Integrin signaling	0.0039	1	8	5	-0.007	-0.002	1000	-1000	-0.033	-1000
HIF-2-alpha transcription factor network	0.0039	1	71	43	-0.084	0.1	1000	-1000	-0.092	-1000
Signaling events mediated by HDAC Class I	0.0039	1	201	104	-0.14	0	1000	-1000	-0.067	-1000
Paxillin-dependent events mediated by a4b1	0.0039	1	55	36	-0.065	0.019	1000	-1000	-0.063	-1000
Atypical NF-kappaB pathway	0.0039	1	47	31	-0.039	0.019	1000	-1000	-0.063	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0039	1	53	27	-0.062	0	1000	-1000	-0.057	-1000
p38 MAPK signaling pathway	0.0039	1	54	44	-0.03	0.029	1000	-1000	-0.062	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	14	23	-0.012	0.031	1000	-1000	-0.069	-1000
Canonical NF-kappaB pathway	0.0000	0	26	39	-0.016	0.066	1000	-1000	-0.086	-1000
Circadian rhythm pathway	0.0000	0	14	22	-0.011	0.035	1000	-1000	-0.051	-1000
Arf6 downstream pathway	0.0000	0	8	43	-0.012	0.018	1000	-1000	-0.041	-1000
EPO signaling pathway	0.0000	0	19	55	-0.007	0.067	1000	-1000	-0.092	-1000
mTOR signaling pathway	0.0000	0	21	53	-0.004	0.027	1000	-1000	-0.057	-1000
ceramide signaling pathway	0.0000	0	19	49	-0.011	0.044	1000	-1000	-0.049	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0000	0	104	125	-0.034	0.079	1000	-1000	-0.097	-1000
VEGFR1 specific signals	0.0000	0	41	56	-0.016	0.048	1000	-1000	-0.083	-1000
Arf1 pathway	0.0000	0	7	54	-0.007	0.016	1000	-1000	-0.039	-1000
Alternative NF-kappaB pathway	0.0000	0	0	13	0	0	1000	-1000	-0.063	-1000
Total	NA	1602	84556	7203	-25	-1000	131000	-131000	-9.4	-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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.99	0.41	-9999	-1.2	194	194
PCK1	-1.1	0.72	-9999	-1.7	151	151
HNF4A	-1.2	0.56	-9999	-1.4	202	202
KCNJ11	-1.3	0.55	-9999	-1.5	207	207
AKT1	-0.37	0.09	-9999	-0.44	118	118
response to starvation	0	0.001	-9999	-10000	0	0
DLK1	-1.2	0.51	-9999	-1.3	209	209
NKX2-1	-0.29	0.18	-9999	-10000	0	0
ACADM	-0.99	0.42	-9999	-1.2	194	194
TAT	-0.53	0.29	-9999	-0.87	88	88
CEBPB	-0.014	0.03	-9999	-0.32	1	1
CEBPA	-0.015	0.046	-9999	-0.38	3	3
TTR	-0.46	0.26	-9999	-0.74	95	95
PKLR	-1.4	0.51	-9999	-1.5	221	221
APOA1	-1.1	0.46	-9999	-1.3	200	200
CPT1C	-0.99	0.42	-9999	-1.2	193	193
ALAS1	-0.35	0.091	-9999	-0.88	1	1
TFRC	-0.75	0.42	-9999	-1	141	141
FOXF1	-0.15	0.3	-9999	-0.75	51	51
NF1	0.01	0.05	-9999	-0.79	1	1
HNF1A (dimer)	-0.079	0.18	-9999	-0.82	13	13
CPT1A	-0.99	0.41	-9999	-1.2	189	189
HMGCS1	-0.99	0.41	-9999	-1.2	194	194
NR3C1	0.012	0.007	-9999	-10000	0	0
CPT1B	-0.99	0.41	-9999	-1.2	194	194
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0	0	-9999	-10000	0	0
GCK	-1	0.43	-9999	-1.2	201	201
CREB1	-0.046	0.057	-9999	-10000	0	0
IGFBP1	-0.31	0.079	-9999	-10000	0	0
PDX1	-0.44	0.15	-9999	-0.91	12	12
UCP2	-0.99	0.41	-9999	-1.2	194	194
ALDOB	-1.5	0.5	-9999	-1.6	233	233
AFP	-0.19	0.24	-9999	-0.49	80	80
BDH1	-1	0.45	-9999	-1.2	194	194
HADH	-1	0.43	-9999	-1.2	198	198
F2	-1.1	0.46	-9999	-1.3	200	200
HNF1A	-0.079	0.18	-9999	-0.83	13	13
G6PC	-0.57	0.66	-9999	-1.5	77	77
SLC2A2	-1.1	0.7	-9999	-1.7	130	130
INS	-0.009	0.007	-9999	-10000	0	0
FOXA1	-0.078	0.21	-9999	-0.5	37	37
FOXA3	-0.31	0.37	-9999	-0.82	79	79
FOXA2	-1.2	0.5	-9999	-1.3	213	213
ABCC8	-1.1	0.43	-9999	-1.2	192	192
ALB	-0.38	0.54	-9999	-0.88	109	109

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.3	0.31	0.64	117	-10000	0	117
KIRREL	-0.052	0.096	-10000	0	-0.38	17	17
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.3	0.31	-10000	0	-0.64	117	117
PLCG1	0	0	-10000	0	-10000	0	0
ARRB2	0	0	-10000	0	-10000	0	0
WASL	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.28	0.3	-10000	0	-0.55	128	128
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.21	0.23	-10000	0	-0.42	128	128
FYN	-0.26	0.28	-10000	0	-0.52	128	128
mol:Ca2+	-0.27	0.29	-10000	0	-0.54	128	128
mol:DAG	-0.27	0.29	-10000	0	-0.54	128	128
NPHS2	-0.13	0.27	-10000	0	-0.85	31	31
mol:IP3	-0.27	0.29	-10000	0	-0.54	128	128
regulation of endocytosis	-0.24	0.26	-10000	0	-0.48	128	128
Nephrin/NEPH1/podocin/Cholesterol	-0.28	0.3	-10000	0	-0.55	128	128
establishment of cell polarity	-0.3	0.31	-10000	0	-0.64	117	117
Nephrin/NEPH1/podocin/NCK1-2	-0.25	0.27	-10000	0	-0.5	128	128
Nephrin/NEPH1/beta Arrestin2	-0.25	0.27	-10000	0	-0.49	128	128
NPHS1	-0.37	0.4	-10000	0	-0.81	116	116
Nephrin/NEPH1/podocin	-0.26	0.28	-10000	0	-0.52	128	128
TJP1	0	0	-10000	0	-10000	0	0
NCK1	0	0	-10000	0	-10000	0	0
NCK2	0	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.28	0.3	-10000	0	-0.55	128	128
CD2AP	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.28	0.3	-10000	0	-0.55	128	128
GRB2	0	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.26	0.28	-10000	0	-0.51	130	130
cytoskeleton organization	-0.28	0.3	-10000	0	-0.55	128	128
Nephrin/NEPH1	-0.23	0.24	-10000	0	-0.48	117	117
Nephrin/NEPH1/ZO-1	-0.25	0.26	-10000	0	-0.52	117	117

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.23	0.26	-9999	-0.53	111	111
E-cadherin/beta catenin	-0.26	0.3	-9999	-0.61	111	111
CTNNB1	0	0	-9999	-10000	0	0
JUP	0	0	-9999	-10000	0	0
CDH1	-0.34	0.39	-9999	-0.79	113	113

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	-0.14	0.16	-10000	0	-0.33	111	111
epithelial cell differentiation	-0.19	0.22	-10000	0	-0.45	111	111
CYFIP2	-0.093	0.26	-10000	0	-0.8	30	30
ENAH	-0.079	0.16	-10000	0	-10000	0	0
EGFR	-0.006	0.057	-10000	0	-0.48	3	3
EPHA2	0	0	-10000	0	-10000	0	0
MYO6	-0.18	0.21	-10000	0	-0.42	111	111
CTNNB1	0	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.061	0.17	-10000	0	-0.53	30	30
AQP5	-0.18	0.21	-10000	0	-0.6	13	13
CTNND1	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.18	0.21	-10000	0	-0.42	111	111
regulation of calcium-dependent cell-cell adhesion	-0.19	0.21	-10000	0	-0.43	116	116
EGF	-0.32	0.39	-10000	0	-0.8	102	102
NCKAP1	0	0	-10000	0	-10000	0	0
AQP3	-0.31	0.31	-10000	0	-0.74	65	65
cortical microtubule organization	-0.19	0.22	-10000	0	-0.45	111	111
GO:0000145	-0.17	0.2	-10000	0	-0.4	111	111
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.2	0.22	-10000	0	-0.45	111	111
MLLT4	-0.003	0.049	-10000	0	-0.8	1	1
ARF6/GDP	-0.15	0.17	-10000	0	-10000	0	0
ARF6	0	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.17	0.19	-10000	0	-0.39	111	111
PVRL2	0	0	-10000	0	-10000	0	0
ZYX	-0.18	0.21	-10000	0	-0.42	111	111
ARF6/GTP	0	0	-10000	0	-10000	0	0
CDH1	-0.34	0.39	-10000	0	-0.79	113	113
EGFR/EGFR/EGF/EGF	-0.34	0.32	-10000	0	-0.56	157	157
RhoA/GDP	-0.18	0.21	-10000	0	-0.42	111	111
actin cytoskeleton organization	-0.17	0.2	-10000	0	-0.4	111	111
IGF-1R heterotetramer	-0.009	0.085	-10000	0	-0.8	3	3
GIT1	0	0	-10000	0	-10000	0	0
IGF1R	-0.009	0.085	-10000	0	-0.8	3	3
IGF1	-0.02	0.1	-10000	0	-0.44	12	12
DIAPH1	-0.1	0.25	-10000	0	-0.78	30	30
Wnt receptor signaling pathway	0.19	0.22	0.45	111	-10000	0	111
RHOA	0	0	-10000	0	-10000	0	0
RhoA/GTP	-0.15	0.18	-10000	0	-10000	0	0
CTNNA1	0	0	-10000	0	-10000	0	0
VCL	-0.18	0.2	-10000	0	-0.41	111	111
EFNA1	0	0	-10000	0	-10000	0	0
LPP	-0.18	0.2	-10000	0	-0.4	111	111
Ephrin A1/EPHA2	-0.18	0.2	-10000	0	-0.41	111	111
SEC6/SEC8	-0.16	0.18	-10000	0	-10000	0	0
MGAT3	-0.2	0.22	-10000	0	-0.43	116	116
HGF/MET	-0.2	0.22	-10000	0	-0.43	121	121
HGF	-0.038	0.16	-10000	0	-0.69	14	14
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.14	0.16	-10000	0	-0.33	111	111
actin cable formation	-0.075	0.16	-10000	0	-0.33	23	23
KIAA1543	-0.35	0.31	-10000	0	-0.55	164	164
KIFC3	-0.19	0.21	-10000	0	-0.43	111	111
NCK1	0	0	-10000	0	-10000	0	0
EXOC3	0	0	-10000	0	-10000	0	0
ACTN1	-0.18	0.21	-10000	0	-0.42	111	111
NCK1/GIT1	0	0	-10000	0	-10000	0	0
mol:GDP	-0.19	0.22	-10000	0	-0.45	111	111
EXOC4	0	0	-10000	0	-10000	0	0
STX4	-0.18	0.21	-10000	0	-0.42	111	111
PIP5K1C	-0.18	0.21	-10000	0	-0.42	111	111
LIMA1	0	0	-10000	0	-10000	0	0
ABI1	0	0	-10000	0	-10000	0	0
ROCK1	-0.13	0.15	-10000	0	-10000	0	0
adherens junction assembly	-0.3	0.3	-10000	0	-0.74	58	58
IGF-1R heterotetramer/IGF1	-0.19	0.21	-10000	0	-0.42	116	116
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.002	0.038	-10000	0	-0.61	1	1
MET	-0.012	0.098	-10000	0	-0.8	4	4
PLEKHA7	-0.19	0.22	-10000	0	-0.44	112	112
mol:GTP	0	0	-10000	0	-10000	0	0
establishment of epithelial cell apical/basal polarity	-0.16	0.18	-10000	0	-10000	0	0
cortical actin cytoskeleton stabilization	-0.14	0.16	-10000	0	-0.33	111	111
regulation of cell-cell adhesion	-0.17	0.2	-10000	0	-0.4	111	111
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.14	0.16	-10000	0	-0.33	111	111

×

IL4-mediated 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
BCL2L1	-0.69	0.43	-10000	0	-1.1	114	114
STAT6 (cleaved dimer)	-0.7	0.42	-10000	0	-1	130	130
IGHG1	-0.24	0.12	-10000	0	-0.38	1	1
IGHG3	-0.67	0.41	-10000	0	-1	125	125
AKT1	-0.3	0.18	-10000	0	-0.65	7	7
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.22	0.14	-10000	0	-1	2	2
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.32	0.18	-10000	0	-0.59	14	14
THY1	-0.69	0.43	-10000	0	-1.1	99	99
MYB	-0.019	0.075	-10000	0	-0.32	15	15
HMGA1	-0.015	0.068	-10000	0	-0.32	12	12
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.39	0.2	-10000	0	-0.58	92	92
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.32	0.18	-10000	0	-0.58	16	16
SP1	0.011	0.006	-10000	0	-10000	0	0
INPP5D	-0.005	0.04	-10000	0	-0.32	4	4
SOCS5	0.026	0.009	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.68	0.42	-10000	0	-1	129	129
SOCS1	-0.45	0.25	-10000	0	-0.73	84	84
SOCS3	-0.32	0.18	-10000	0	-0.65	7	7
FCER2	-0.5	0.28	-10000	0	-0.8	83	83
PARP14	0	0	-10000	0	-10000	0	0
CCL17	-0.7	0.43	-10000	0	-1.1	105	105
GRB2	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.26	0.14	-10000	0	-0.69	3	3
T cell proliferation	-0.68	0.44	-10000	0	-1.1	103	103
IL4R/JAK1	-0.69	0.43	-10000	0	-1.1	113	113
EGR2	-0.7	0.44	-10000	0	-1.1	104	104
JAK2	-0.024	0.031	-10000	0	-0.39	1	1
JAK3	-0.013	0.09	-10000	0	-0.32	20	20
PIK3R1	-0.004	0.053	-10000	0	-0.56	2	2
JAK1	0.001	0.005	-10000	0	-10000	0	0
COL1A2	-0.25	0.18	-10000	0	-0.82	7	7
CCL26	-0.71	0.45	-10000	0	-1.1	109	109
IL4R	-0.73	0.46	-10000	0	-1.2	114	114
PTPN6	0.025	0.023	-10000	0	-0.31	1	1
IL13RA2	-0.86	0.59	-10000	0	-1.4	122	122
IL13RA1	-0.022	0.022	-10000	0	-10000	0	0
IRF4	-0.14	0.095	-10000	0	-10000	0	0
ARG1	-0.17	0.092	-10000	0	-10000	0	0
CBL	-0.36	0.2	-10000	0	-0.57	59	59
GTF3A	0.01	0.007	-10000	0	-10000	0	0
PIK3CA	0	0	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.034	0.031	-10000	0	-0.3	1	1
IRF4/BCL6	-0.13	0.078	-10000	0	-10000	0	0
CD40LG	-0.007	0.081	-10000	0	-0.34	14	14
MAPK14	-0.36	0.2	-10000	0	-0.55	70	70
mitosis	-0.29	0.17	-10000	0	-0.6	8	8
STAT6	-0.79	0.51	-10000	0	-1.2	125	125
SPI1	-0.013	0.079	-10000	0	-0.32	16	16
RPS6KB1	-0.28	0.16	-10000	0	-0.66	4	4
STAT6 (dimer)	-0.79	0.51	-10000	0	-1.2	125	125
STAT6 (dimer)/PARP14	-0.73	0.47	-10000	0	-1.1	124	124
mast cell activation	0.017	0.008	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.3	0.17	-10000	0	-0.65	8	8
FRAP1	-0.3	0.18	-10000	0	-0.64	8	8
LTA	-0.7	0.43	-10000	0	-1.2	90	90
FES	0	0	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0.77	0.49	1.2	125	-10000	0	125
CCL11	-0.89	0.61	-10000	0	-1.5	124	124
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.3	0.17	-10000	0	-0.67	7	7
IL2RG	-0.028	0.12	-10000	0	-0.36	29	29
IL10	-0.7	0.44	-10000	0	-1.2	97	97
IRS1	-0.001	0.02	-10000	0	-0.32	1	1
IRS2	0	0	-10000	0	-10000	0	0
IL4	-0.17	0.079	-10000	0	-10000	0	0
IL5	-0.7	0.43	-10000	0	-1.2	86	86
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.56	0.31	-10000	0	-0.83	120	120
COL1A1	-0.28	0.15	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.7	0.45	-10000	0	-1.2	85	85
IL2R gamma/JAK3	-0.043	0.11	-10000	0	-0.45	12	12
TFF3	-0.86	0.61	-10000	0	-1.4	124	124
ALOX15	-0.7	0.43	-10000	0	-1.1	104	104
MYBL1	-0.02	0.077	-10000	0	-0.32	16	16
T-helper 2 cell differentiation	-0.56	0.32	-10000	0	-0.85	116	116
SHC1	0	0	-10000	0	-10000	0	0
CEBPB	0.006	0.021	-10000	0	-0.32	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.3	0.17	-10000	0	-0.59	11	11
mol:PI-3-4-5-P3	-0.3	0.18	-10000	0	-0.64	8	8
PI3K	-0.31	0.18	-10000	0	-0.7	7	7
DOK2	-0.014	0.065	-10000	0	-0.32	11	11
ETS1	0.024	0.011	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.24	0.14	-10000	0	-0.69	3	3
ITGB3	-0.7	0.44	-10000	0	-1.2	88	88
PIGR	-1.3	0.59	-10000	0	-1.6	203	203
IGHE	0.058	0.027	-10000	0	-10000	0	0
MAPKKK cascade	-0.24	0.14	-10000	0	-0.67	3	3
BCL6	0	0	-10000	0	-10000	0	0
OPRM1	-0.7	0.43	-10000	0	-1.1	107	107
RETNLB	-0.7	0.43	-10000	0	-1.1	116	116
SELP	-0.91	0.63	-10000	0	-1.5	117	117
AICDA	-0.67	0.42	-10000	0	-1.1	103	103

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0	0	-9999	-10000	0	0
EGFR	-0.006	0.057	-9999	-0.48	3	3
EGF/EGFR	-0.19	0.23	-9999	-0.45	108	108
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.18	0.22	-9999	-0.45	103	103
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.002	0.028	-9999	-0.32	2	2
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.32	0.39	-9999	-0.8	102	102
EGF/EGFR dimer/SHC	-0.21	0.26	-9999	-0.53	103	103
mol:GDP	-0.18	0.22	-9999	-0.44	103	103
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.025	0.14	-9999	-0.8	8	8
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.16	0.2	-9999	-0.41	103	103
SHC1	0	0	-9999	-10000	0	0
HRAS/GDP	-0.17	0.2	-9999	-0.42	103	103
FRAP1	-0.17	0.21	-9999	-0.43	103	103
EGF/EGFR dimer	-0.24	0.3	-9999	-0.61	103	103
SOS1	0	0	-9999	-10000	0	0
GRB2	0	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.02	0.11	-9999	-0.61	8	8

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.005	0.008	-9999	-10000	0	0
RAS family/GTP	-0.24	0.21	-9999	-0.65	32	32
NFATC4	-0.22	0.16	-9999	-0.48	27	27
ERBB2IP	0.01	0.007	-9999	-10000	0	0
HSP90 (dimer)	0	0	-9999	-10000	0	0
mammary gland morphogenesis	-0.3	0.21	-9999	-0.43	182	182
JUN	-0.057	0.066	-9999	-0.24	9	9
HRAS	0	0	-9999	-10000	0	0
DOCK7	-0.29	0.2	-9999	-0.56	39	39
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.37	0.27	-9999	-0.52	182	182
AKT1	0.003	0.005	-9999	-10000	0	0
BAD	0.005	0.008	-9999	-10000	0	0
MAPK10	-0.21	0.14	-9999	-0.37	90	90
mol:GTP	0	0.001	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.33	0.24	-9999	-0.47	182	182
RAF1	-0.21	0.21	-9999	-0.66	26	26
ErbB2/ErbB3/neuregulin 2	-0.36	0.27	-9999	-0.53	176	176
STAT3	-0.004	0.004	-9999	-10000	0	0
cell migration	-0.16	0.12	-9999	-0.31	69	69
mol:PI-3-4-5-P3	-0.005	0.003	-9999	-10000	0	0
cell proliferation	-0.19	0.18	-9999	-0.52	33	33
FOS	-0.13	0.15	-9999	-0.53	17	17
NRAS	0	0	-9999	-10000	0	0
mol:Ca2+	-0.3	0.21	-9999	-0.43	182	182
MAPK3	-0.19	0.17	-9999	-0.51	29	29
MAPK1	-0.19	0.17	-9999	-0.48	36	36
JAK2	-0.29	0.2	-9999	-0.54	43	43
NF2	-0.016	0.011	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.3	0.26	-9999	-0.43	179	179
NRG1	-0.1	0.26	-9999	-0.72	37	37
GRB2/SOS1	0	0	-9999	-10000	0	0
MAPK8	-0.24	0.16	-9999	-0.34	180	180
MAPK9	-0.14	0.094	-9999	-0.29	25	25
ERBB2	-0.022	0.12	-9999	-0.63	9	9
ERBB3	-0.52	0.38	-9999	-0.8	169	169
SHC1	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
apoptosis	0.026	0.018	-9999	-10000	0	0
STAT3 (dimer)	-0.004	0.003	-9999	-10000	0	0
RNF41	0.007	0.011	-9999	-10000	0	0
FRAP1	0.003	0.004	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.2	0.14	-9999	-0.42	27	27
ErbB2/ErbB2/HSP90 (dimer)	-0.019	0.099	-9999	-0.54	9	9
CHRNA1	-0.15	0.13	-9999	-0.36	27	27
myelination	-0.21	0.17	-9999	-0.47	27	27
PPP3CB	-0.26	0.18	-9999	-0.5	42	42
KRAS	0	0	-9999	-10000	0	0
RAC1-CDC42/GDP	-0.26	0.23	-9999	-0.65	36	36
NRG2	-0.046	0.19	-9999	-0.8	15	15
mol:GDP	-0.3	0.25	-9999	-0.43	179	179
SOS1	0	0	-9999	-10000	0	0
MAP2K2	-0.19	0.19	-9999	-0.61	24	24
SRC	0	0	-9999	-10000	0	0
mol:cAMP	-0.004	0.002	-9999	-10000	0	0
PTPN11	-0.29	0.2	-9999	-0.48	63	63
MAP2K1	-0.22	0.19	-9999	-0.54	36	36
heart morphogenesis	-0.3	0.21	-9999	-0.43	182	182
RAS family/GDP	-0.25	0.22	-9999	-0.73	27	27
GRB2	0	0	-9999	-10000	0	0
PRKACA	-0.022	0.015	-9999	-10000	0	0
CHRNE	-0.008	0.029	-9999	-0.12	12	12
HSP90AA1	0	0	-9999	-10000	0	0
activation of caspase activity	-0.003	0.005	-9999	-10000	0	0
nervous system development	-0.3	0.21	-9999	-0.43	182	182
CDC42	0	0	-9999	-10000	0	0

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.075	0.2	-10000	0	-0.63	6	6
IHH	-0.16	0.33	-10000	0	-0.81	52	52
SHH Np/Cholesterol/GAS1	-0.079	0.18	-10000	0	-0.48	41	41
LRPAP1	0	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.079	0.18	0.48	41	-10000	0	41
SMO/beta Arrestin2	-0.13	0.21	-10000	0	-0.52	51	51
SMO	-0.14	0.22	-10000	0	-0.55	52	52
AKT1	-0.056	0.092	-10000	0	-10000	0	0
ARRB2	0	0	-10000	0	-10000	0	0
BOC	-0.012	0.082	-10000	0	-0.46	7	7
ADRBK1	0	0	-10000	0	-10000	0	0
heart looping	-0.11	0.23	-10000	0	-0.54	52	52
STIL	-0.18	0.22	-10000	0	-0.52	58	58
DHH N/PTCH2	-0.043	0.14	-10000	0	-0.62	13	13
DHH N/PTCH1	-0.12	0.2	-10000	0	-0.47	59	59
PIK3CA	0	0	-10000	0	-10000	0	0
DHH	-0.042	0.17	-10000	0	-0.68	16	16
PTHLH	-0.096	0.27	-10000	0	-1.2	6	6
determination of left/right symmetry	-0.11	0.23	-10000	0	-0.54	52	52
PIK3R1	-0.004	0.053	-10000	0	-0.56	2	2
skeletal system development	-0.095	0.26	-10000	0	-1.1	6	6
IHH N/Hhip	-0.24	0.32	-10000	0	-0.61	100	100
DHH N/Hhip	-0.16	0.27	-10000	0	-0.63	59	59
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.11	0.23	-10000	0	-0.54	52	52
pancreas development	-0.17	0.31	-10000	0	-0.68	64	64
HHAT	0	0	-10000	0	-10000	0	0
PI3K	-0.003	0.04	-10000	0	-0.61	1	1
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.006	0.057	-10000	0	-0.48	3	3
somite specification	-0.11	0.23	-10000	0	-0.54	52	52
SHH Np/Cholesterol/PTCH1	-0.16	0.22	-10000	0	-0.52	42	42
SHH Np/Cholesterol/PTCH2	-0.085	0.18	-10000	0	-0.48	41	41
SHH Np/Cholesterol/Megalin	-0.3	0.3	-10000	0	-0.55	142	142
SHH	-0.087	0.22	-10000	0	-0.61	40	40
catabolic process	-0.087	0.21	-10000	0	-0.48	51	51
SMO/Vitamin D3	-0.16	0.23	-10000	0	-0.52	51	51
SHH Np/Cholesterol/Hhip	-0.18	0.26	-10000	0	-0.54	80	80
LRP2	-0.37	0.4	-10000	0	-0.8	121	121
receptor-mediated endocytosis	-0.3	0.28	-10000	0	-0.75	51	51
SHH Np/Cholesterol/BOC	-0.083	0.18	-10000	0	-0.49	42	42
SHH Np/Cholesterol/CDO	-0.081	0.18	-10000	0	-0.48	41	41
mesenchymal cell differentiation	0.18	0.26	0.54	80	-10000	0	80
mol:Vitamin D3	-0.13	0.24	-10000	0	-0.45	79	79
IHH N/PTCH2	-0.12	0.22	-10000	0	-0.51	59	59
CDON	-0.008	0.063	-10000	0	-0.42	5	5
IHH N/PTCH1	-0.11	0.2	-10000	0	-0.48	51	51
Megalin/LRPAP1	-0.29	0.3	-10000	0	-0.61	121	121
PTCH2	-0.018	0.083	-10000	0	-0.36	13	13
SHH Np/Cholesterol	-0.077	0.18	-10000	0	-0.49	40	40
PTCH1	-0.087	0.21	-10000	0	-0.48	51	51
HHIP	-0.17	0.31	-10000	0	-0.68	64	64

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.044	0.11	-9999	-0.32	35	35
GPC2	-0.1	0.15	-9999	-0.32	84	84
GPC2/Midkine	-0.095	0.13	-9999	-0.41	18	18
neuron projection morphogenesis	-0.095	0.13	-9999	-0.4	18	18

×

Signaling mediated by p38-alpha and p38-beta

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.23	0.53	-9999	-1.3	52	52
MKNK1	0	0	-9999	-10000	0	0
MAPK14	-0.045	0.13	-9999	-0.3	54	54
ATF2/c-Jun	-0.049	0.095	-9999	-0.5	1	1
MAPK11	-0.046	0.14	-9999	-0.52	2	2
MITF	-0.046	0.16	-9999	-0.36	55	55
MAPKAPK5	-0.044	0.16	-9999	-0.36	54	54
KRT8	-0.4	0.33	-9999	-0.54	197	197
MAPKAPK3	0	0	-9999	-10000	0	0
MAPKAPK2	0	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.068	0.2	-9999	-0.45	54	54
CEBPB	-0.045	0.16	-9999	-0.36	54	54
SLC9A1	-0.044	0.16	-9999	-0.36	54	54
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.038	0.16	-9999	-0.34	54	54
p38alpha-beta/MNK1	-0.075	0.14	-9999	-0.5	3	3
JUN	-0.02	0.11	-9999	-0.5	1	1
PPARGC1A	-0.15	0.3	-9999	-0.5	90	90
USF1	-0.044	0.16	-9999	-0.36	54	54
RAB5/GDP/GDI1	-0.053	0.1	-9999	-0.34	2	2
NOS2	-0.05	0.19	-9999	-1	3	3
DDIT3	-0.045	0.16	-9999	-0.36	54	54
RAB5A	0	0	-9999	-10000	0	0
HSPB1	-0.027	0.13	-9999	-0.38	2	2
p38alpha-beta/HBP1	-0.075	0.14	-9999	-0.5	3	3
CREB1	-0.046	0.17	-9999	-0.37	54	54
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	-0.031	0.14	-9999	-0.48	2	2
RPS6KA4	-0.044	0.16	-9999	-0.36	54	54
PLA2G4A	-0.057	0.2	-9999	-0.64	14	14
GDI1	-0.044	0.16	-9999	-0.36	54	54
TP53	-0.058	0.2	-9999	-0.44	54	54
RPS6KA5	-0.048	0.16	-9999	-0.36	56	56
ESR1	-0.067	0.2	-9999	-0.42	56	56
HBP1	0	0	-9999	-10000	0	0
MEF2C	-0.044	0.16	-9999	-0.36	54	54
MEF2A	-0.044	0.16	-9999	-0.36	54	54
EIF4EBP1	-0.046	0.17	-9999	-0.37	54	54
KRT19	-0.28	0.32	-9999	-0.5	150	150
ELK4	-0.044	0.16	-9999	-0.36	54	54
ATF6	-0.044	0.16	-9999	-0.36	54	54
ATF1	-0.046	0.17	-9999	-0.37	54	54
p38alpha-beta/MAPKAPK2	-0.075	0.14	-9999	-0.5	3	3
p38alpha-beta/MAPKAPK3	-0.075	0.14	-9999	-0.5	3	3

×

E-cadherin signaling in the nascent adherens junction

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.25	0.29	-9999	-0.58	111	111
KLHL20	-0.074	0.084	-9999	-0.35	1	1
CYFIP2	-0.093	0.26	-9999	-0.8	30	30
Rac1/GDP	-0.12	0.2	-9999	-0.4	3	3
ENAH	-0.25	0.29	-9999	-0.58	111	111
AP1M1	0	0	-9999	-10000	0	0
RAP1B	-0.002	0.028	-9999	-0.32	2	2
RAP1A	0	0	-9999	-10000	0	0
CTNNB1	0	0	-9999	-10000	0	0
CDC42/GTP	-0.12	0.14	-9999	-0.37	2	2
ABI1/Sra1/Nap1	-0.064	0.077	-9999	-0.24	24	24
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.21	0.24	-9999	-0.48	111	111
RAPGEF1	-0.18	0.26	-9999	-0.49	111	111
CTNND1	0	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.26	0.3	-9999	-0.6	111	111
CRK	-0.21	0.28	-9999	-0.54	111	111
E-cadherin/gamma catenin/alpha catenin	-0.23	0.26	-9999	-0.53	111	111
alphaE/beta7 Integrin	-0.002	0.018	-9999	-10000	0	0
IQGAP1	0	0	-9999	-10000	0	0
NCKAP1	0	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	-0.003	0.033	-9999	-0.48	1	1
DLG1	-0.25	0.29	-9999	-0.58	111	111
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.089	0.1	-9999	-10000	0	0
MLLT4	-0.003	0.049	-9999	-0.8	1	1
ARF6/GTP/NME1/Tiam1	-0.005	0.025	-9999	-10000	0	0
PI3K	-0.12	0.13	-9999	-10000	0	0
ARF6	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.26	0.3	-9999	-0.61	111	111
TIAM1	-0.01	0.056	-9999	-0.32	8	8
E-cadherin(dimer)/Ca2+	-0.2	0.22	-9999	-0.45	111	111
AKT1	-0.065	0.073	-9999	-10000	0	0
PIK3R1	-0.004	0.053	-9999	-0.56	2	2
CDH1	-0.34	0.39	-9999	-0.79	113	113
RhoA/GDP	-0.12	0.2	-9999	-0.4	3	3
actin cytoskeleton organization	-0.055	0.062	-9999	-0.24	1	1
CDC42/GDP	-0.12	0.2	-9999	-0.4	3	3
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.15	0.17	-9999	-0.34	111	111
ITGB7	-0.002	0.028	-9999	-0.32	2	2
RAC1	0	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.21	0.24	-9999	-0.48	111	111
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.2	0.23	-9999	-0.46	111	111
mol:GDP	-0.15	0.23	-9999	-0.41	111	111
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	0	0	-9999	-10000	0	0
p120 catenin/RhoA/GDP	-0.15	0.17	-9999	-0.4	3	3
RAC1/GTP/IQGAP1	0	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0
CTNNA1	0	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	-0.035	0.042	-9999	-0.29	1	1
NME1	0	0	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	-0.25	0.29	-9999	-0.58	111	111
regulation of cell-cell adhesion	-0.11	0.12	-9999	-0.32	2	2
WASF2	-0.033	0.039	-9999	-0.14	1	1
Rap1/GTP	-0.14	0.16	-9999	-0.43	2	2
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.19	0.22	-9999	-0.45	111	111
CCND1	-0.043	0.051	-9999	-0.38	1	1
VAV2	-0.2	0.28	-9999	-0.52	111	111
RAP1/GDP	-0.14	0.16	-9999	-0.43	2	2
adherens junction assembly	-0.24	0.28	-9999	-0.56	111	111
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0	0	-9999	-10000	0	0
PIP5K1C	0	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.18	0.21	-9999	-0.42	111	111
E-cadherin/beta catenin	-0.21	0.24	-9999	-0.5	111	111
mol:GTP	0	0	-9999	-10000	0	0
SRC	-0.25	0.29	-9999	-0.58	111	111
PIK3CA	0	0	-9999	-10000	0	0
Rac1/GTP	-0.12	0.14	-9999	-0.66	1	1
E-cadherin/beta catenin/alpha catenin	-0.23	0.26	-9999	-0.52	111	111
ITGAE	0	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.27	0.31	-9999	-0.62	111	111

×

TCGA08_retinoblastoma

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
CDKN2B	-0.041	0.12	-10000	0	-0.34	31	31
CDKN2C	0.024	0.07	-10000	0	-0.38	6	6
CDKN2A	-0.25	0.15	-10000	0	-0.34	194	194
CCND2	0.045	0.05	0.15	30	-0.12	4	34
RB1	-0.049	0.046	-10000	0	-0.23	4	4
CDK4	0.053	0.046	0.24	4	-10000	0	4
CDK6	0.051	0.05	0.24	4	-0.18	1	5
G1/S progression	0.049	0.046	0.23	4	-10000	0	4

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.088	0.14	-9999	-0.38	42	42
FZD6	-0.012	0.098	-9999	-0.8	4	4
WNT6	-0.01	0.056	-9999	-0.32	8	8
WNT4	-0.07	0.21	-9999	-0.61	30	30
FZD3	-0.069	0.22	-9999	-0.78	23	23
WNT5A	-0.088	0.14	-9999	-0.32	71	71
WNT11	-0.075	0.14	-9999	-0.33	59	59

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	-0.006	0.034	-9999	-10000	0	0
VLDLR	-0.046	0.19	-9999	-0.8	15	15
CRKL	0	0	-9999	-10000	0	0
LRPAP1	0	0	-9999	-10000	0	0
FYN	-0.001	0.02	-9999	-0.32	1	1
ITGA3	-0.028	0.15	-9999	-0.8	9	9
RELN/VLDLR/Fyn	-0.16	0.26	-9999	-0.57	70	70
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.003	0.039	-9999	-0.45	2	2
AKT1	-0.1	0.16	-9999	-0.35	71	71
MAP2K7	0	0	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0
DAB1	-0.042	0.11	-9999	-0.32	34	34
RELN/LRP8/DAB1	-0.15	0.22	-9999	-0.5	66	66
LRPAP1/LRP8	-0.012	0.049	-9999	-10000	0	0
RELN/LRP8/DAB1/Fyn	-0.14	0.2	-9999	-0.48	64	64
DAB1/alpha3/beta1 Integrin	-0.16	0.22	-9999	-0.46	81	81
long-term memory	-0.2	0.25	-9999	-0.51	91	91
DAB1/LIS1	-0.15	0.22	-9999	-0.48	72	72
DAB1/CRLK/C3G	-0.14	0.22	-9999	-0.47	70	70
PIK3CA	0	0	-9999	-10000	0	0
DAB1/NCK2	-0.15	0.22	-9999	-0.49	72	72
ARHGEF2	0	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.14	0.28	-9999	-0.64	56	56
CDK5R1	-0.009	0.052	-9999	-0.32	7	7
RELN	-0.2	0.34	-9999	-0.76	67	67
PIK3R1	-0.004	0.053	-9999	-0.56	2	2
RELN/LRP8/Fyn	-0.14	0.23	-9999	-0.53	64	64
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.21	0.26	-9999	-0.53	91	91
MAPK8	-0.003	0.049	-9999	-0.8	1	1
RELN/VLDLR/DAB1	-0.17	0.25	-9999	-0.54	73	73
ITGB1	0	0	-9999	-10000	0	0
MAP1B	-0.16	0.23	-9999	-0.5	72	72
RELN/LRP8	-0.14	0.23	-9999	-0.53	64	64
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.14	0.2	-9999	-0.48	64	64
PI3K	-0.003	0.04	-9999	-0.61	1	1
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.021	0.11	-9999	-0.61	9	9
RAP1A	-0.14	0.2	-9999	-0.64	15	15
PAFAH1B1	0	0	-9999	-10000	0	0
MAPK8IP1	-0.003	0.049	-9999	-0.8	1	1
CRLK/C3G	0	0	-9999	-10000	0	0
GRIN2B	0	0	-9999	-10000	0	0
NCK2	0	0	-9999	-10000	0	0
neuron differentiation	-0.06	0.1	-9999	-0.33	10	10
neuron adhesion	-0.14	0.19	-9999	-0.6	15	15
LRP8	-0.019	0.075	-9999	-0.32	15	15
GSK3B	-0.094	0.15	-9999	-0.51	11	11
RELN/VLDLR/DAB1/Fyn	-0.16	0.23	-9999	-0.51	70	70
MAP3K11	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.11	0.17	-9999	-0.38	71	71
CDK5	0	0	-9999	-10000	0	0
MAPT	-0.27	0.37	-9999	-0.74	99	99
neuron migration	-0.09	0.22	-9999	-0.44	63	63
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.061	0.1	-9999	-0.33	10	10
RELN/VLDLR	-0.15	0.25	-9999	-0.54	70	70

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.16	0.1	-10000	0	-0.22	194	194
TP53	-0.017	0.053	-10000	0	-0.19	1	1
Senescence	-0.017	0.053	-10000	0	-0.19	1	1
Apoptosis	-0.017	0.053	-10000	0	-0.19	1	1
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.031	0.11	0.32	1	-0.22	3	4
MDM4	0	0	-10000	0	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.033	0.053	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.065	0.14	-9999	-0.43	16	16
JUN	-0.069	0.13	-9999	-0.58	6	6
HRAS	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.13	0.22	-9999	-0.57	45	45
RAP1A	0	0	-9999	-10000	0	0
FRS2	-0.025	0.086	-9999	-0.32	20	20
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.13	0.22	-9999	-0.57	45	45
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.12	0.2	-9999	-0.52	45	45
RHOA	0	0	-9999	-10000	0	0
RAP1A/GTP	-0.12	0.21	-9999	-0.53	45	45
GRB7	-0.14	0.3	-9999	-0.79	45	45
RET51/GFRalpha1/GDNF	-0.13	0.22	-9999	-0.57	45	45
MAPKKK cascade	-0.097	0.18	-9999	-0.46	45	45
BCAR1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.12	0.2	-9999	-0.52	45	45
lamellipodium assembly	-0.065	0.13	-9999	-0.34	44	44
RET51/GFRalpha1/GDNF/SHC	-0.13	0.22	-9999	-0.57	45	45
PIK3CA	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.12	0.2	-9999	-0.53	43	43
RET9/GFRalpha1/GDNF/Shank3	-0.12	0.2	-9999	-0.52	45	45
MAPK3	-0.11	0.2	-9999	-0.5	45	45
DOK1	0	0	-9999	-10000	0	0
DOK6	-0.25	0.37	-9999	-0.8	81	81
PXN	0	0	-9999	-10000	0	0
neurite development	-0.15	0.21	-9999	-0.62	31	31
DOK5	-0.036	0.16	-9999	-0.66	14	14
GFRA1	-0.15	0.3	-9999	-0.69	55	55
MAPK8	-0.074	0.14	-9999	-0.46	17	17
HRAS/GTP	-0.11	0.21	-9999	-0.53	45	45
tube development	-0.11	0.18	-9999	-0.5	43	43
MAPK1	-0.11	0.2	-9999	-0.5	45	45
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.074	0.13	-9999	-0.36	43	43
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
PDLIM7	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.26	0.32	-9999	-0.61	103	103
SHC1	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.14	0.24	-9999	-0.59	45	45
RET51/GFRalpha1/GDNF/Dok5	-0.16	0.25	-9999	-0.62	51	51
PRKCA	-0.006	0.07	-9999	-0.8	2	2
HRAS/GDP	0	0	-9999	-10000	0	0
CREB1	-0.078	0.16	-9999	-0.41	43	43
PIK3R1	-0.004	0.053	-9999	-0.56	2	2
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.07	0.13	-9999	-0.36	43	43
RET51/GFRalpha1/GDNF/Grb7	-0.22	0.29	-9999	-0.6	81	81
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.035	0.14	-9999	-0.51	18	18
DOK4	-0.006	0.07	-9999	-0.8	2	2
JNK cascade	-0.043	0.14	-9999	-0.56	6	6
RET9/GFRalpha1/GDNF/FRS2	-0.13	0.19	-9999	-0.51	47	47
SHANK3	0	0	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.07	0.13	-9999	-0.36	43	43
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.084	0.15	-9999	-0.39	45	45
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.08	0.15	-9999	-0.39	45	45
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.085	0.18	-9999	-0.42	45	45
PI3K	-0.1	0.21	-9999	-0.54	44	44
SOS1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.11	0.18	-9999	-0.5	43	43
GRB10	0	0	-9999	-10000	0	0
activation of MAPKK activity	-0.079	0.14	-9999	-0.36	43	43
RET51/GFRalpha1/GDNF/FRS2	-0.14	0.22	-9999	-0.57	46	46
GAB1	0	0	-9999	-10000	0	0
IRS1	-0.001	0.02	-9999	-0.32	1	1
IRS2	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.085	0.18	-9999	-0.42	45	45
RET51/GFRalpha1/GDNF/PKC alpha	-0.14	0.23	-9999	-0.58	47	47
GRB2	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GDNF	-0.065	0.13	-9999	-0.32	52	52
RAC1	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.14	0.22	-9999	-0.57	45	45
Rac1/GTP	-0.078	0.16	-9999	-0.42	44	44
RET9/GFRalpha1/GDNF	-0.13	0.21	-9999	-0.57	45	45
GFRalpha1/GDNF	-0.15	0.24	-9999	-0.64	45	45

×

Syndecan-1-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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.001	0.02	-9999	-0.32	1	1
CCL5	-0.052	0.12	-9999	-0.32	42	42
SDCBP	0	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.14	0.16	-9999	-0.37	51	51
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.13	0.14	-9999	-0.56	6	6
Syndecan-1/Syntenin	-0.13	0.14	-9999	-0.44	16	16
MAPK3	-0.11	0.13	-9999	-0.51	6	6
HGF/MET	-0.038	0.14	-9999	-0.61	15	15
TGFB1/TGF beta receptor Type II	-0.001	0.02	-9999	-0.32	1	1
BSG	0	0	-9999	-10000	0	0
keratinocyte migration	-0.13	0.14	-9999	-0.43	16	16
Syndecan-1/RANTES	-0.16	0.15	-9999	-0.44	27	27
Syndecan-1/CD147	-0.12	0.14	-9999	-0.54	6	6
Syndecan-1/Syntenin/PIP2	-0.13	0.14	-9999	-0.42	16	16
LAMA5	0	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.13	0.13	-9999	-0.41	16	16
MMP7	-0.29	0.38	-9999	-0.79	95	95
HGF	-0.038	0.16	-9999	-0.69	14	14
Syndecan-1/CASK	-0.13	0.15	-9999	-0.36	51	51
Syndecan-1/HGF/MET	-0.15	0.16	-9999	-0.51	22	22
regulation of cell adhesion	-0.093	0.13	-9999	-0.49	6	6
HPSE	-0.02	0.077	-9999	-0.32	16	16
positive regulation of cell migration	-0.14	0.16	-9999	-0.37	51	51
SDC1	-0.14	0.16	-9999	-0.38	51	51
Syndecan-1/Collagen	-0.14	0.16	-9999	-0.37	51	51
PPIB	0	0	-9999	-10000	0	0
MET	-0.012	0.098	-9999	-0.8	4	4
PRKACA	0	0	-9999	-10000	0	0
MMP9	-0.13	0.16	-9999	-0.32	105	105
MAPK1	-0.11	0.13	-9999	-0.51	6	6
homophilic cell adhesion	-0.14	0.16	-9999	-0.37	51	51
MMP1	-0.095	0.18	-9999	-0.37	66	66

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.035	0.093	-9999	-0.57	5	5
alphaM/beta2 Integrin/GPIbA	-0.017	0.065	-9999	-0.52	3	3
alphaM/beta2 Integrin/proMMP-9	-0.083	0.11	-9999	-0.4	12	12
PLAUR	-0.045	0.11	-9999	-0.32	36	36
HMGB1	-0.004	0.011	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.015	0.062	-9999	-0.61	2	2
AGER	-0.004	0.011	-9999	-10000	0	0
RAP1A	0	0	-9999	-10000	0	0
SELPLG	-0.007	0.048	-9999	-0.32	6	6
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.031	0.085	-9999	-0.7	2	2
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.13	0.16	-9999	-0.32	105	105
CYR61	-0.009	0.085	-9999	-0.8	3	3
TLN1	0	0	-9999	-10000	0	0
Rap1/GTP	-0.1	0.14	-9999	-0.5	14	14
RHOA	0	0	-9999	-10000	0	0
P-selectin oligomer	-0.24	0.36	-9999	-0.8	78	78
MYH2	-0.3	0.27	-9999	-0.51	133	133
MST1R	-0.022	0.082	-9999	-0.32	18	18
leukocyte activation during inflammatory response	-0.16	0.24	-9999	-0.5	79	79
APOB	-0.18	0.33	-9999	-0.78	59	59
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.037	0.12	-9999	-0.38	25	25
JAM3	0	0	-9999	-10000	0	0
GP1BA	-0.002	0.028	-9999	-0.32	2	2
alphaM/beta2 Integrin/CTGF	-0.031	0.11	-9999	-0.55	10	10
alphaM/beta2 Integrin	-0.12	0.16	-9999	-0.34	62	62
JAM3 homodimer	0	0	-9999	-10000	0	0
ICAM2	0	0	-9999	-10000	0	0
ICAM1	-0.002	0.028	-9999	-0.32	2	2
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.12	0.16	-9999	-0.34	62	62
cell adhesion	-0.016	0.065	-9999	-0.51	3	3
NFKB1	-0.049	0.13	-9999	-0.84	2	2
THY1	-0.003	0.049	-9999	-0.8	1	1
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.18	0.28	-9999	-0.58	78	78
alphaM/beta2 Integrin/LRP/tPA	-0.031	0.1	-9999	-0.58	7	7
IL6	-0.054	0.31	-9999	-0.96	26	26
ITGB2	-0.015	0.059	-9999	-0.32	9	9
elevation of cytosolic calcium ion concentration	-0.037	0.082	-9999	-0.52	3	3
alphaM/beta2 Integrin/JAM2/JAM3	-0.012	0.055	-9999	-0.56	2	2
JAM2	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/ICAM1	-0.026	0.077	-9999	-0.47	5	5
alphaM/beta2 Integrin/uPA/Plg	-0.12	0.21	-9999	-0.5	55	55
RhoA/GTP	-0.16	0.2	-9999	-0.42	63	63
positive regulation of phagocytosis	-0.085	0.12	-9999	-0.46	14	14
Ron/MSP	-0.022	0.083	-9999	-0.61	3	3
alphaM/beta2 Integrin/uPAR/uPA	-0.037	0.083	-9999	-0.52	3	3
alphaM/beta2 Integrin/uPAR	-0.038	0.084	-9999	-0.44	5	5
PLAU	-0.012	0.062	-9999	-0.32	10	10
PLAT	-0.02	0.12	-9999	-0.73	7	7
actin filament polymerization	-0.28	0.26	-9999	-0.49	134	134
MST1	-0.009	0.085	-9999	-0.8	3	3
alphaM/beta2 Integrin/lipoprotein(a)	-0.16	0.24	-9999	-0.51	79	79
TNF	0.004	0.14	-9999	-0.75	2	2
RAP1B	-0.002	0.028	-9999	-0.32	2	2
alphaM/beta2 Integrin/uPA	-0.021	0.072	-9999	-0.61	2	2
fibrinolysis	-0.12	0.2	-9999	-0.5	55	55
HCK	-0.015	0.068	-9999	-0.32	12	12
dendritic cell antigen processing and presentation	-0.12	0.16	-9999	-0.34	62	62
VTN	-0.18	0.33	-9999	-0.79	59	59
alphaM/beta2 Integrin/CYR61	-0.021	0.082	-9999	-0.56	5	5
LPA	-0.086	0.25	-9999	-0.8	28	28
LRP1	-0.017	0.073	-9999	-0.32	14	14
cell migration	-0.089	0.11	-9999	-0.5	7	7
FN1	-0.06	0.12	-9999	-0.32	48	48
alphaM/beta2 Integrin/Thy1	-0.017	0.069	-9999	-0.58	3	3
MPO	-0.042	0.11	-9999	-0.32	34	34
KNG1	-0.18	0.34	-9999	-0.8	60	60
RAP1/GDP	-0.001	0.015	-9999	-10000	0	0
ROCK1	-0.13	0.2	-9999	-0.5	26	26
ELA2	0	0	-9999	-10000	0	0
PLG	-0.17	0.32	-9999	-0.8	54	54
CTGF	-0.025	0.14	-9999	-0.8	8	8
alphaM/beta2 Integrin/Hck	-0.023	0.078	-9999	-0.4	8	8
ITGAM	-0.012	0.078	-9999	-0.68	3	3
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.16	0.23	-9999	-0.5	79	79
HP	-0.029	0.091	-9999	-0.32	23	23
leukocyte adhesion	-0.024	0.073	-9999	-0.64	2	2
SELP	-0.24	0.37	-9999	-0.8	78	78

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	-0.071	0.083	-10000	0	-0.43	1	1
adherens junction organization	-0.12	0.17	-10000	0	-0.31	111	111
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.069	0.084	-10000	0	-0.45	2	2
FMN1	-0.14	0.16	-10000	0	-0.42	14	14
mol:IP3	-0.075	0.087	-10000	0	-0.4	1	1
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.14	0.16	-10000	0	-0.32	111	111
CTNNB1	0.009	0.01	-10000	0	-10000	0	0
AKT1	-0.086	0.099	-10000	0	-0.39	1	1
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.24	0.28	-10000	0	-0.56	111	111
CTNND1	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.11	0.16	-10000	0	-0.3	111	111
VASP	-0.13	0.15	-10000	0	-0.38	1	1
ZYX	-0.13	0.15	-10000	0	-0.38	1	1
JUB	-0.13	0.15	-10000	0	-0.38	1	1
EGFR(dimer)	-0.13	0.16	-10000	0	-0.52	3	3
E-cadherin/beta catenin-gamma catenin	-0.22	0.25	-10000	0	-0.51	111	111
mol:PI-3-4-5-P3	-0.093	0.11	-10000	0	-0.37	2	2
PIK3CA	0	0	-10000	0	-10000	0	0
PI3K	-0.094	0.11	-10000	0	-0.38	2	2
FYN	-0.21	0.2	-10000	0	-0.48	53	53
mol:Ca2+	-0.074	0.085	-10000	0	-0.39	1	1
JUP	0.009	0.01	-10000	0	-10000	0	0
PIK3R1	-0.004	0.053	-10000	0	-0.56	2	2
mol:DAG	-0.075	0.087	-10000	0	-0.4	1	1
CDH1	-0.34	0.39	-10000	0	-0.79	113	113
RhoA/GDP	-0.069	0.084	-10000	0	-0.54	1	1
establishment of polarity of embryonic epithelium	-0.11	0.16	-10000	0	-0.38	1	1
SRC	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
EGFR	-0.006	0.057	-10000	0	-0.48	3	3
CASR	-0.27	0.22	-10000	0	-0.48	124	124
RhoA/GTP	-0.066	0.076	-10000	0	-0.35	1	1
AKT2	-0.086	0.099	-10000	0	-0.39	1	1
actin cable formation	-0.12	0.17	-10000	0	-0.42	12	12
apoptosis	0.084	0.097	0.41	1	-10000	0	1
CTNNA1	0	0	-10000	0	-10000	0	0
mol:GDP	-0.076	0.091	-10000	0	-0.49	2	2
PIP5K1A	-0.13	0.15	-10000	0	-0.3	111	111
PLCG1	-0.076	0.088	-10000	0	-0.41	1	1
Rac1/GTP	-0.12	0.14	-10000	0	-0.47	3	3
homophilic cell adhesion	-0.001	0.003	-10000	0	-10000	0	0

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.089	0.18	-9999	-0.44	52	52
NF kappa B1 p50/RelA/I kappa B alpha	-0.077	0.16	-9999	-0.59	4	4
alphaV/beta3 Integrin/Osteopontin/Src	-0.11	0.24	-9999	-0.6	49	49
AP1	-0.11	0.19	-9999	-0.72	9	9
ILK	-0.094	0.19	-9999	-0.47	52	52
bone resorption	-0.081	0.17	-9999	-0.86	3	3
PTK2B	0	0	-9999	-10000	0	0
PYK2/p130Cas	-0.09	0.19	-9999	-0.44	52	52
ITGAV	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.002	0.022	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.11	0.22	-9999	-0.53	52	52
MAP3K1	-0.096	0.2	-9999	-0.48	52	52
JUN	-0.002	0.028	-9999	-0.32	2	2
MAPK3	-0.047	0.2	-9999	-0.44	52	52
MAPK1	-0.047	0.2	-9999	-0.44	52	52
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
MAPK8	-0.055	0.2	-9999	-0.44	53	53
ITGB3	-0.015	0.11	-9999	-0.79	5	5
NFKBIA	-0.038	0.2	-9999	-0.43	52	52
FOS	-0.049	0.19	-9999	-0.8	16	16
CD44	-0.004	0.034	-9999	-0.32	3	3
CHUK	0	0	-9999	-10000	0	0
PLAU	-0.03	0.18	-9999	-0.72	2	2
NF kappa B1 p50/RelA	-0.073	0.15	-9999	-0.72	2	2
BCAR1	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.012	0.083	-9999	-0.6	5	5
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.1	0.21	-9999	-0.5	52	52
VAV3	-0.062	0.22	-9999	-0.47	52	52
MAP3K14	-0.062	0.21	-9999	-0.48	52	52
ROCK2	0	0	-9999	-10000	0	0
SPP1	-0.15	0.31	-9999	-0.79	49	49
RAC1	0	0	-9999	-10000	0	0
Rac1/GTP	-0.087	0.18	-9999	-0.43	52	52
MMP2	-0.11	0.17	-9999	-0.62	11	11

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.063	0.069	-9999	-10000	0	0
STMN1	-0.076	0.12	-9999	-0.41	4	4
Aurora B/RasGAP/Survivin	-0.14	0.15	-9999	-0.32	86	86
Chromosomal passenger complex/Cul3 protein complex	-0.066	0.11	-9999	-0.38	22	22
BIRC5	-0.16	0.16	-9999	-0.32	128	128
DES	-0.31	0.33	-9999	-0.66	124	124
Aurora C/Aurora B/INCENP	-0.055	0.082	-9999	-0.3	3	3
Aurora B/TACC1	-0.064	0.086	-9999	-10000	0	0
Aurora B/PP2A	-0.079	0.1	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.008	0.02	-9999	-10000	0	0
mitotic metaphase/anaphase transition	-0.002	0.003	-9999	-10000	0	0
NDC80	-0.14	0.17	-9999	-0.4	57	57
Cul3 protein complex	-0.045	0.15	-9999	-0.53	22	22
KIF2C	-0.042	0.042	-9999	-10000	0	0
PEBP1	0	0	-9999	-10000	0	0
KIF20A	-0.17	0.16	-9999	-0.32	135	135
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.079	0.1	-9999	-10000	0	0
SEPT1	-0.005	0.04	-9999	-0.32	4	4
SMC2	0	0	-9999	-10000	0	0
SMC4	-0.002	0.028	-9999	-0.32	2	2
NSUN2/NPM1/Nucleolin	0	0.024	-9999	-10000	0	0
PSMA3	0	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.002	0.002	-9999	-10000	0	0
H3F3B	-0.03	0.049	-9999	-10000	0	0
AURKB	-0.13	0.16	-9999	-0.32	107	107
AURKC	-0.004	0.034	-9999	-0.32	3	3
CDCA8	-0.11	0.16	-9999	-0.33	89	89
cytokinesis	-0.1	0.085	-9999	-10000	0	0
Aurora B/Septin1	-0.084	0.093	-9999	-10000	0	0
AURKA	-0.015	0.071	-9999	-0.32	13	13
INCENP	-0.003	0.029	-9999	-0.33	2	2
KLHL13	-0.068	0.22	-9999	-0.8	22	22
BUB1	-0.13	0.16	-9999	-0.32	103	103
hSgo1/Aurora B/Survivin	-0.15	0.17	-9999	-0.35	95	95
EVI5	0.001	0.002	-9999	-10000	0	0
RhoA/GTP	-0.074	0.09	-9999	-0.38	2	2
SGOL1	-0.051	0.12	-9999	-0.32	41	41
CENPA	-0.049	0.066	-9999	-10000	0	0
NCAPG	-0.15	0.16	-9999	-0.32	124	124
Aurora B/HC8 Proteasome	-0.079	0.1	-9999	-10000	0	0
NCAPD2	-0.001	0.02	-9999	-0.32	1	1
Aurora B/PP1-gamma	-0.079	0.1	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
NCAPH	-0.12	0.15	-9999	-0.32	94	94
NPM1	-0.019	0.03	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
KLHL9	0	0	-9999	-10000	0	0
mitotic prometaphase	-0.005	0.005	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.078	0.1	-9999	-10000	0	0
PPP1CC	0	0	-9999	-10000	0	0
Centraspindlin	-0.084	0.1	-9999	-0.33	16	16
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.019	0.03	-9999	-10000	0	0
MYLK	-0.11	0.17	-9999	-0.47	46	46
KIF23	-0.038	0.1	-9999	-0.32	30	30
VIM	-0.072	0.11	-9999	-10000	0	0
RACGAP1	-0.003	0.029	-9999	-0.33	2	2
mitosis	0	0	-9999	-10000	0	0
NCL	-0.019	0.03	-9999	-10000	0	0
Chromosomal passenger complex	-0.079	0.08	-9999	-0.23	3	3
Chromosomal passenger complex/EVI5	-0.13	0.2	-9999	-0.4	67	67
TACC1	0	0	-9999	-10000	0	0
PPP2R5D	0	0	-9999	-10000	0	0
CUL3	0	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	-0.056	0.2	-10000	0	-0.8	18	18
GNB1/GNG2	-0.041	0.075	-10000	0	-0.19	50	50
AKT1	-0.013	0.12	-10000	0	-0.22	52	52
EGF	-0.32	0.39	-10000	0	-0.8	102	102
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	-0.004	0.01	-10000	0	-10000	0	0
mol:Ca2+	-0.02	0.16	-10000	0	-0.3	58	58
LYN	-0.004	0.01	-10000	0	-10000	0	0
RhoA/GTP	-0.028	0.051	-10000	0	-0.14	10	10
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.022	0.17	-10000	0	-0.35	51	51
GNG2	-0.007	0.048	-10000	0	-0.32	6	6
ARRB2	0	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.014	0.058	-10000	0	-0.48	1	1
G beta5/gamma2	-0.053	0.099	-10000	0	-0.24	50	50
PRKCH	-0.027	0.17	-10000	0	-0.36	51	51
DNM1	-0.004	0.034	-10000	0	-0.32	3	3
TXA2/TP beta/beta Arrestin3	-0.003	0.009	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	-0.043	0.11	-10000	0	-0.32	35	35
G12 family/GTP	-0.068	0.12	-10000	0	-0.3	52	52
ADRBK1	0	0	-10000	0	-10000	0	0
ADRBK2	0	0	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0	0	-10000	0	-10000	0	0
mol:GDP	0.003	0.091	0.24	2	-10000	0	2
mol:NADP	0	0	-10000	0	-10000	0	0
RAB11A	0	0	-10000	0	-10000	0	0
PRKG1	-0.02	0.087	-10000	0	-0.35	15	15
mol:IP3	-0.033	0.19	-10000	0	-0.38	58	58
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	-0.059	0.25	-10000	0	-0.52	58	58
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.015	0.035	-10000	0	-10000	0	0
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.009	0.024	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
PTGIR	-0.006	0.044	-10000	0	-0.32	5	5
PRKCB1	-0.034	0.19	-10000	0	-0.37	58	58
GNAQ	0	0	-10000	0	-10000	0	0
mol:L-citrulline	0	0	-10000	0	-10000	0	0
TXA2/TXA2-R family	-0.057	0.25	-10000	0	-0.54	52	52
LCK	-0.017	0.041	-10000	0	-0.37	1	1
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.008	0.02	-10000	0	-10000	0	0
TXA2-R family/G12 family/GDP/G beta/gamma	-0.001	0.004	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.007	0.017	-10000	0	-10000	0	0
MAPK14	-0.002	0.12	-10000	0	-0.23	51	51
TGM2/GTP	-0.047	0.23	-10000	0	-0.45	58	58
MAPK11	-0.003	0.12	-10000	0	-0.23	50	50
ARHGEF1	-0.033	0.077	-10000	0	-0.18	27	27
GNAI2	0	0	-10000	0	-10000	0	0
JNK cascade	-0.031	0.19	-10000	0	-0.39	52	52
RAB11/GDP	0	0	-10000	0	-10000	0	0
ICAM1	-0.014	0.14	-10000	0	-0.28	51	51
cAMP biosynthetic process	-0.031	0.18	-10000	0	-0.36	58	58
Gq family/GTP/EBP50	-0.021	0.07	-10000	0	-0.3	6	6
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	-0.004	0.01	-10000	0	-10000	0	0
GNB5	0	0	-10000	0	-10000	0	0
GNB1	0	0	-10000	0	-10000	0	0
EGF/EGFR	-0.021	0.076	-10000	0	-10000	0	0
VCAM1	-0.027	0.17	-10000	0	-0.35	51	51
TP beta/Gq family/GDP/G beta5/gamma2	0.014	0.058	-10000	0	-0.48	1	1
platelet activation	-0.005	0.16	-10000	0	-0.3	51	51
PGI2/IP	-0.004	0.03	-10000	0	-10000	0	0
PRKACA	-0.012	0.029	-10000	0	-10000	0	0
Gq family/GDP/G beta5/gamma2	0.012	0.057	-10000	0	-0.44	1	1
TXA2/TP beta/beta Arrestin2	0	0.004	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.01	0.024	-10000	0	-10000	0	0
mol:DAG	-0.041	0.21	-10000	0	-0.42	58	58
EGFR	-0.006	0.057	-10000	0	-0.48	3	3
TXA2/TP alpha	-0.051	0.24	-10000	0	-0.49	58	58
Gq family/GTP	-0.017	0.074	-10000	0	-0.29	17	17
YES1	-0.004	0.01	-10000	0	-10000	0	0
GNAI2/GTP	-0.006	0.013	-10000	0	-10000	0	0
PGD2/DP	-0.03	0.075	-10000	0	-0.22	35	35
SLC9A3R1	-0.012	0.098	-10000	0	-0.8	4	4
FYN	-0.005	0.012	-10000	0	-10000	0	0
mol:NO	0	0	-10000	0	-10000	0	0
GNA15	-0.006	0.044	-10000	0	-0.32	5	5
PGK/cGMP	-0.011	0.051	-10000	0	-0.54	1	1
RhoA/GDP	0	0	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.037	0.1	-10000	0	-0.4	18	18
NOS3	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
PRKCA	-0.029	0.18	-10000	0	-0.36	52	52
PRKCB	-0.031	0.18	-10000	0	-0.38	51	51
PRKCE	-0.027	0.18	-10000	0	-0.36	51	51
PRKCD	-0.032	0.19	-10000	0	-0.39	51	51
PRKCG	-0.038	0.2	-10000	0	-0.4	53	53
muscle contraction	-0.047	0.24	-10000	0	-0.5	52	52
PRKCZ	-0.05	0.2	-10000	0	-0.38	55	55
ARR3	0	0	-10000	0	-10000	0	0
TXA2/TP beta	-0.007	0.017	-10000	0	-10000	0	0
PRKCQ	-0.036	0.19	-10000	0	-0.38	53	53
MAPKKK cascade	-0.046	0.22	-10000	0	-0.45	58	58
SELE	-0.038	0.19	-10000	0	-0.4	51	51
TP beta/GNAI2/GDP/G beta/gamma	-0.009	0.022	-10000	0	-10000	0	0
ROCK1	0	0	-10000	0	-10000	0	0
GNA14	-0.049	0.19	-10000	0	-0.8	16	16
chemotaxis	-0.07	0.29	-10000	0	-0.63	51	51
GNA12	0	0	-10000	0	-10000	0	0
GNA13	0	0	-10000	0	-10000	0	0
GNA11	-0.003	0.049	-10000	0	-0.8	1	1
Rac1/GTP	0	0	-10000	0	-10000	0	0

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.034	0.098	-9999	-0.32	27	27
GNB1/GNG2	-0.075	0.12	-9999	-0.41	16	16
mol:DAG	-0.067	0.11	-9999	-0.46	6	6
PLCG1	-0.068	0.12	-9999	-0.48	6	6
YES1	-0.079	0.13	-9999	-0.35	42	42
FZD3	-0.069	0.22	-9999	-0.78	23	23
FZD6	-0.012	0.098	-9999	-0.8	4	4
G protein	-0.069	0.12	-9999	-0.51	5	5
MAP3K7	-0.068	0.18	-9999	-0.49	29	29
mol:Ca2+	-0.065	0.11	-9999	-0.45	6	6
mol:IP3	-0.067	0.11	-9999	-0.46	6	6
NLK	-0.004	0.011	-9999	-10000	0	0
GNB1	0	0	-9999	-10000	0	0
CAMK2A	-0.083	0.2	-9999	-0.53	31	31
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.088	0.14	-9999	-0.38	42	42
CSNK1A1	0	0	-9999	-10000	0	0
GNAS	-0.079	0.13	-9999	-0.35	42	42
GO:0007205	-0.044	0.12	-9999	-0.48	5	5
WNT6	-0.01	0.056	-9999	-0.32	8	8
WNT4	-0.07	0.21	-9999	-0.61	30	30
NFAT1/CK1 alpha	-0.074	0.12	-9999	-0.46	8	8
GNG2	-0.007	0.048	-9999	-0.32	6	6
WNT5A	-0.088	0.14	-9999	-0.32	71	71
WNT11	-0.075	0.14	-9999	-0.33	59	59
CDC42	-0.072	0.12	-9999	-0.4	16	16

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.02	0.1	-9999	-0.53	10	10
PTK2	-0.15	0.18	-9999	-0.52	22	22
IGF1R	-0.009	0.085	-9999	-0.8	3	3
PI4KB	0	0	-9999	-10000	0	0
MFGE8	0	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
CDKN1B	-0.14	0.26	-9999	-0.63	58	58
VEGFA	0	0	-9999	-10000	0	0
ILK	-0.14	0.26	-9999	-0.63	58	58
ROCK1	0	0	-9999	-10000	0	0
AKT1	-0.14	0.25	-9999	-0.58	58	58
PTK2B	-0.009	0.061	-9999	-0.44	5	5
alphaV/beta3 Integrin/JAM-A	-0.12	0.21	-9999	-0.48	64	64
CBL	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.2	0.26	-9999	-0.53	98	98
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.017	0.087	-9999	-0.57	5	5
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.064	0.12	-9999	-0.54	1	1
alphaV/beta3 Integrin/Syndecan-1	-0.018	0.092	-9999	-0.53	8	8
PI4KA	0	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.048	0.13	-9999	-0.66	7	7
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.11	0.22	-9999	-0.54	52	52
RPS6KB1	-0.044	0.12	-9999	-0.64	6	6
TLN1	0	0	-9999	-10000	0	0
MAPK3	-0.078	0.17	-9999	-0.78	10	10
GPR124	-0.001	0.02	-9999	-0.32	1	1
MAPK1	-0.078	0.17	-9999	-0.78	10	10
PXN	0	0	-9999	-10000	0	0
PIK3R1	-0.004	0.053	-9999	-0.56	2	2
alphaV/beta3 Integrin/Tumstatin	-0.3	0.28	-9999	-0.54	144	144
cell adhesion	-0.16	0.2	-9999	-0.41	98	98
ANGPTL3	-0.29	0.38	-9999	-0.8	93	93
VEGFR2 homodimer/VEGFA homodimer/Src	0	0	-9999	-10000	0	0
IGF-1R heterotetramer	-0.009	0.085	-9999	-0.8	3	3
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	0	0	-9999	-10000	0	0
ITGB3	-0.015	0.11	-9999	-0.8	5	5
IGF1	-0.02	0.1	-9999	-0.44	12	12
RAC1	0	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.011	0.073	-9999	-0.52	5	5
apoptosis	0	0	-9999	-10000	0	0
CD47	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.01	0.072	-9999	-0.53	5	5
VCL	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.097	0.12	-9999	-0.59	7	7
CSF1	-0.006	0.044	-9999	-0.32	5	5
PIK3C2A	-0.14	0.26	-9999	-0.63	58	58
PI4 Kinase/Pyk2	-0.098	0.18	-9999	-0.76	4	4
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.009	0.066	-9999	-0.48	5	5
FAK1/Vinculin	-0.12	0.14	-9999	-0.41	22	22
alphaV beta3/Integrin/ppsTEM5	-0.011	0.073	-9999	-0.53	5	5
RHOA	0	0	-9999	-10000	0	0
VTN	-0.18	0.33	-9999	-0.79	59	59
BCAR1	0	0	-9999	-10000	0	0
FGF2	-0.015	0.11	-9999	-0.8	5	5
F11R	0.006	0.086	-9999	-0.61	5	5
alphaV/beta3 Integrin/Lactadherin	-0.01	0.072	-9999	-0.53	5	5
alphaV/beta3 Integrin/TGFBR2	-0.01	0.072	-9999	-0.53	5	5
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.003	0.019	-9999	-10000	0	0
HSP90AA1	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.009	0.067	-9999	-0.48	5	5
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.06	0.12	-9999	-0.32	48	48
alphaV/beta3 Integrin/Pyk2	-0.009	0.062	-9999	-0.45	5	5
SDC1	-0.012	0.09	-9999	-0.61	5	5
VAV3	-0.005	0.034	-9999	-0.45	1	1
PTPN11	0	0	-9999	-10000	0	0
IRS1	-0.001	0.02	-9999	-0.32	1	1
FAK1/Paxillin	-0.12	0.14	-9999	-0.41	22	22
cell migration	-0.1	0.13	-9999	-0.42	7	7
ITGAV	0	0	-9999	-10000	0	0
PI3K	-0.11	0.19	-9999	-0.43	65	65
SPP1	-0.15	0.31	-9999	-0.8	49	49
KDR	0	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0	0	-9999	-10000	0	0
COL4A3	-0.44	0.4	-9999	-0.8	144	144
angiogenesis	-0.072	0.21	-9999	-0.76	11	11
Rac1/GTP	-0.004	0.03	-9999	-0.41	1	1
EDIL3	-0.17	0.17	-9999	-0.33	130	130
cell proliferation	-0.01	0.072	-9999	-0.52	5	5

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0	0	-9999	-10000	0	0
VLDLR	-0.046	0.19	-9999	-0.8	15	15
LRPAP1	0	0	-9999	-10000	0	0
NUDC	0	0	-9999	-10000	0	0
RELN/LRP8	-0.14	0.23	-9999	-0.53	64	64
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.12	0.21	-9999	-0.48	62	62
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	-0.042	0.11	-9999	-0.32	34	34
IQGAP1	0	0	-9999	-10000	0	0
PLA2G7	-0.11	0.15	-9999	-0.32	91	91
CALM1	0	0	-9999	-10000	0	0
DYNLT1	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.012	0.049	-9999	-10000	0	0
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0	0	-9999	-10000	0	0
CDK5R1	-0.009	0.052	-9999	-0.32	7	7
LIS1/Poliovirus Protein 3A	0	0	-9999	-10000	0	0
CDK5R2	-0.055	0.12	-9999	-0.32	44	44
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.18	0.27	-9999	-0.58	73	73
YWHAE	0	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.1	0.16	-9999	-0.46	12	12
MAP1B	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.11	0.18	-9999	-0.43	62	62
RELN	-0.2	0.34	-9999	-0.76	67	67
PAFAH/LIS1	-0.058	0.078	-9999	-10000	0	0
LIS1/CLIP170	0	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.076	0.13	-9999	-0.42	1	1
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.1	0.17	-9999	-0.36	70	70
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.11	0.17	-9999	-0.41	62	62
LIS1/IQGAP1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.019	0	-9999	-10000	0	0
PAFAH1B3	-0.003	0.049	-9999	-0.8	1	1
PAFAH1B2	0	0	-9999	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0	0	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.097	0.16	-9999	-0.47	5	5
LRP8	-0.019	0.075	-9999	-0.32	15	15
NDEL1/Katanin 60	-0.1	0.16	-9999	-0.46	12	12
P39/CDK5	-0.13	0.19	-9999	-0.44	62	62
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0	0	-9999	-10000	0	0
CDK5	-0.12	0.19	-9999	-0.45	62	62
PPP2R5D	0	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0	-9999	-10000	0	0
CSNK2A1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.15	0.23	-9999	-0.5	70	70
RELN/VLDLR	-0.15	0.25	-9999	-0.54	70	70
CDC42	0	0	-9999	-10000	0	0

×

Coregulation of Androgen receptor activity

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	-0.01	0.052	-9999	-0.8	1	1
SVIL	-0.012	0.071	-9999	-0.8	2	2
ZNF318	0.02	0.056	-9999	-10000	0	0
JMJD2C	-0.035	0.064	-9999	-0.14	72	72
T-DHT/AR/Ubc9	-0.1	0.13	-9999	-0.42	24	24
CARM1	0	0	-9999	-10000	0	0
PRDX1	0.001	0.003	-9999	-10000	0	0
PELP1	0.004	0.011	-9999	-10000	0	0
CTNNB1	-0.004	0.013	-9999	-10000	0	0
AKT1	0.006	0.017	-9999	-10000	0	0
PTK2B	-0.003	0.009	-9999	-10000	0	0
MED1	0.006	0.018	-9999	-10000	0	0
MAK	0.015	0.07	-9999	-0.32	4	4
response to oxidative stress	0.001	0.003	-9999	-10000	0	0
HIP1	-0.009	0.052	-9999	-0.8	1	1
GSN	-0.006	0.018	-9999	-10000	0	0
NCOA2	-0.021	0.096	-9999	-0.39	14	14
NCOA6	-0.006	0.016	-9999	-10000	0	0
DNA-PK	0.019	0.054	-9999	-10000	0	0
NCOA4	0	0	-9999	-10000	0	0
PIAS3	-0.004	0.013	-9999	-10000	0	0
cell proliferation	-0.025	0.06	-9999	-10000	0	0
XRCC5	0.005	0.014	-9999	-10000	0	0
UBE3A	-0.01	0.029	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.12	0.14	-9999	-0.46	30	30
FHL2	-0.045	0.066	-9999	-10000	0	0
RANBP9	-0.006	0.016	-9999	-10000	0	0
JMJD1A	-0.082	0.08	-9999	-0.15	148	148
CDK6	-0.002	0.05	-9999	-0.8	1	1
TGFB1I1	-0.006	0.017	-9999	-10000	0	0
T-DHT/AR/CyclinD1	-0.11	0.13	-9999	-0.44	25	25
XRCC6	0.005	0.014	-9999	-10000	0	0
T-DHT/AR	-0.18	0.17	-9999	-0.4	70	70
CTDSP1	0	0.001	-9999	-10000	0	0
CTDSP2	0.002	0.072	-9999	-0.32	9	9
BRCA1	-0.009	0.036	-9999	-0.36	2	2
TCF4	0.008	0.034	-9999	-0.32	1	1
CDKN2A	-0.24	0.14	-9999	-0.32	193	193
SRF	0.02	0.017	-9999	-10000	0	0
NKX3-1	-0.22	0.3	-9999	-1	21	21
KLK3	-0.16	0.5	-9999	-1.6	28	28
TMF1	0	0	-9999	-10000	0	0
HNRNPA1	0.008	0.021	-9999	-10000	0	0
AOF2	-0.008	0.023	-9999	-0.073	28	28
APPL1	0.027	0.032	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.097	0.13	-9999	-0.42	24	24
AR	-0.11	0.18	-9999	-0.53	31	31
UBA3	0	0.001	-9999	-10000	0	0
PATZ1	0.008	0.021	-9999	-10000	0	0
PAWR	-0.019	0.12	-9999	-0.8	6	6
PRKDC	0.005	0.014	-9999	-10000	0	0
PA2G4	0.009	0.026	-9999	-10000	0	0
UBE2I	0	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.092	0.12	-9999	-0.39	25	25
RPS6KA3	-0.006	0.018	-9999	-10000	0	0
T-DHT/AR/ARA70	-0.1	0.13	-9999	-0.43	24	24
LATS2	0.008	0.021	-9999	-10000	0	0
T-DHT/AR/PRX1	-0.085	0.12	-9999	-0.4	22	22
Cyclin D3/CDK11 p58	-0.003	0.026	-9999	-0.21	4	4
VAV3	-0.01	0.06	-9999	-0.49	3	3
KLK2	-0.38	0.53	-9999	-1.2	72	72
CASP8	0.003	0.008	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.1	0.13	-9999	-0.47	20	20
TMPRSS2	-0.7	0.59	-9999	-1.2	144	144
CCND1	-0.006	0.053	-9999	-0.56	2	2
PIAS1	-0.01	0.029	-9999	-10000	0	0
mol:T-DHT	-0.058	0.048	-9999	-0.088	173	173
CDC2L1	0.001	0.002	-9999	-10000	0	0
PIAS4	-0.016	0.047	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.1	0.13	-9999	-0.43	25	25
CMTM2	-0.004	0.045	-9999	-0.32	5	5
SNURF	-0.019	0.12	-9999	-0.8	6	6
ZMIZ1	-0.044	0.038	-9999	-10000	0	0
CCND3	-0.005	0.039	-9999	-0.32	4	4
TGIF1	0.008	0.021	-9999	-10000	0	0
FKBP4	-0.006	0.016	-9999	-10000	0	0

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	-0.002	0.028	-9999	-0.32	2	2
Aurora C/Aurora B/INCENP	-0.064	0.076	-9999	-0.31	3	3
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.018	0.021	-9999	-10000	0	0
AURKB	-0.13	0.16	-9999	-0.32	107	107
AURKC	-0.004	0.034	-9999	-0.32	3	3

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.16	0.23	-9999	-0.52	63	63
SMAD6-7/SMURF1	0	0	-9999	-10000	0	0
NOG	-0.044	0.11	-9999	-0.32	35	35
SMAD9	-0.024	0.085	-9999	-0.5	7	7
SMAD4	0	0	-9999	-10000	0	0
SMAD5	-0.001	0.1	-9999	-0.34	21	21
BMP7/USAG1	-0.4	0.36	-9999	-0.7	138	138
SMAD5/SKI	-0.031	0.087	-9999	-0.34	3	3
SMAD1	0.028	0.029	-9999	-10000	0	0
BMP2	-0.012	0.09	-9999	-0.61	5	5
SMAD1/SMAD1/SMAD4	-0.002	0.007	-9999	-10000	0	0
BMPR1A	-0.003	0.049	-9999	-0.8	1	1
BMPR1B	-0.074	0.22	-9999	-0.64	30	30
BMPR1A-1B/BAMBI	-0.14	0.25	-9999	-0.56	62	62
AHSG	-0.006	0.044	-9999	-0.32	5	5
CER1	-0.002	0.028	-9999	-0.32	2	2
BMP2-4/CER1	-0.013	0.071	-9999	-0.53	4	4
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.03	0.076	-9999	-0.34	1	1
BMP2-4 (homodimer)	-0.014	0.081	-9999	-0.61	4	4
RGMB	-0.002	0.028	-9999	-0.32	2	2
BMP6/BMPR2/BMPR1A-1B	-0.045	0.13	-9999	-0.48	21	21
RGMA	-0.019	0.1	-9999	-0.45	11	11
SMURF1	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.032	0.08	-9999	-0.32	2	2
BMP2-4/USAG1	-0.24	0.26	-9999	-0.53	113	113
SMAD6/SMURF1/SMAD5	-0.031	0.087	-9999	-0.34	3	3
SOSTDC1	-0.35	0.39	-9999	-0.77	117	117
BMP7/BMPR2/BMPR1A-1B	-0.15	0.23	-9999	-0.52	63	63
SKI	0	0	-9999	-10000	0	0
BMP6 (homodimer)	-0.002	0.028	-9999	-0.32	2	2
HFE2	-0.025	0.086	-9999	-0.32	20	20
ZFYVE16	0	0	-9999	-10000	0	0
MAP3K7	0	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.031	0.12	-9999	-0.56	12	12
SMAD5/SMAD5/SMAD4	-0.031	0.087	-9999	-0.34	3	3
MAPK1	0	0	-9999	-10000	0	0
TAK1/TAB family	-0.024	0.066	-9999	-10000	0	0
BMP7 (homodimer)	-0.19	0.3	-9999	-0.57	87	87
NUP214	0	0	-9999	-10000	0	0
BMP6/FETUA	-0.006	0.034	-9999	-10000	0	0
SMAD1/SKI	-0.004	0.014	-9999	-10000	0	0
SMAD6	0	0	-9999	-10000	0	0
CTDSP2	-0.012	0.062	-9999	-0.32	10	10
BMP2-4/FETUA	-0.015	0.073	-9999	-0.53	4	4
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.19	0.24	-9999	-0.41	120	120
BMPR2 (homodimer)	0	0	-9999	-10000	0	0
GADD34/PP1CA	0	0	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.058	0.17	-9999	-0.61	21	21
CHRDL1	-0.12	0.27	-9999	-0.71	43	43
ENDOFIN/SMAD1	-0.004	0.014	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.003	0.01	-9999	-10000	0	0
SMAD6/SMURF1	0	0	-9999	-10000	0	0
BAMBI	-0.14	0.3	-9999	-0.8	45	45
SMURF2	0	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.088	0.19	-9999	-0.53	39	39
BMP2-4/GREM1	-0.12	0.16	-9999	-0.52	30	30
SMAD7	0	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.021	0.078	-9999	-0.46	7	7
SMAD1/SMAD6	-0.004	0.014	-9999	-10000	0	0
TAK1/SMAD6	0	0	-9999	-10000	0	0
BMP7	-0.19	0.3	-9999	-0.57	87	87
BMP6	-0.002	0.028	-9999	-0.32	2	2
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.026	0.068	-9999	-0.26	2	2
PPM1A	0	0	-9999	-10000	0	0
SMAD1/SMURF2	-0.004	0.014	-9999	-10000	0	0
SMAD7/SMURF1	0	0	-9999	-10000	0	0
CTDSPL	0	0	-9999	-10000	0	0
PPP1CA	0	0	-9999	-10000	0	0
XIAP	0	0	-9999	-10000	0	0
CTDSP1	0	0	-9999	-10000	0	0
PPP1R15A	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.038	0.085	-9999	-0.32	4	4
CHRD	-0.029	0.15	-9999	-0.75	10	10
BMPR2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.034	0.084	-9999	-0.32	3	3
BMP4	-0.008	0.063	-9999	-0.42	5	5
FST	-0.045	0.12	-9999	-0.35	33	33
BMP2-4/NOG	-0.034	0.095	-9999	-0.45	8	8
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.14	0.21	-9999	-0.49	63	63

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.017	0	-9999	-10000	0	0
ADCY5	-0.19	0.27	-9999	-0.53	97	97
ADCY6	0.017	0.012	-9999	-10000	0	0
ADCY7	0.017	0	-9999	-10000	0	0
ADCY1	-0.007	0.063	-9999	-10000	0	0
ADCY2	-0.06	0.17	-9999	-0.53	27	27
ADCY3	0.016	0.017	-9999	-10000	0	0
ADCY8	-0.053	0.17	-9999	-0.53	27	27
PRKCE	0.009	0	-9999	-10000	0	0
ADCY9	0.017	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.066	0.1	-9999	-0.28	29	29

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.043	0.1	-10000	0	-0.44	6	6
FYN	-0.009	0.15	-10000	0	-0.44	18	18
LAT/GRAP2/SLP76	-0.037	0.13	-10000	0	-0.47	14	14
IKBKB	0	0	-10000	0	-10000	0	0
AKT1	0.003	0.12	-10000	0	-0.35	16	16
B2M	0	0	-10000	0	-10000	0	0
IKBKG	-0.013	0.031	-10000	0	-10000	0	0
MAP3K8	-0.003	0.049	-10000	0	-0.8	1	1
mol:Ca2+	-0.033	0.052	-10000	0	-0.12	68	68
integrin-mediated signaling pathway	-0.001	0.011	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.009	0.16	-10000	0	-0.47	19	19
TRPV6	-0.21	0.36	-10000	0	-0.79	70	70
CD28	-0.024	0.084	-10000	0	-0.32	19	19
SHC1	-0.011	0.15	-10000	0	-0.43	17	17
receptor internalization	-0.017	0.14	-10000	0	-0.38	22	22
PRF1	-0.017	0.13	-10000	0	-0.7	1	1
KRAS	0	0	-10000	0	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
COT/AKT1	0.007	0.1	-10000	0	-0.3	12	12
LAT	-0.016	0.16	-10000	0	-0.45	19	19
EntrezGene:6955	0	0.003	-10000	0	-10000	0	0
CD3D	-0.052	0.14	-10000	0	-0.37	37	37
CD3E	-0.053	0.15	-10000	0	-0.42	33	33
CD3G	-0.085	0.14	-10000	0	-0.32	68	68
RASGRP2	-0.006	0.031	-10000	0	-0.18	7	7
RASGRP1	0.01	0.12	-10000	0	-0.38	11	11
HLA-A	0	0	-10000	0	-10000	0	0
RASSF5	-0.001	0.02	-10000	0	-0.32	1	1
RAP1A/GTP/RAPL	-0.001	0.011	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.02	0.042	-10000	0	-0.11	4	4
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.023	0.055	-10000	0	-0.22	8	8
PRKCA	-0.016	0.081	-10000	0	-0.28	10	10
GRAP2	-0.011	0.059	-10000	0	-0.32	9	9
mol:IP3	0.021	0.17	0.26	61	-0.4	12	73
EntrezGene:6957	0	0.003	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.019	0.12	-10000	0	-0.32	23	23
ORAI1	0.1	0.16	0.38	68	-10000	0	68
CSK	-0.013	0.15	-10000	0	-0.42	21	21
B7 family/CD28	-0.056	0.14	-10000	0	-0.49	19	19
CHUK	0	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.023	0.16	-10000	0	-0.44	25	25
PTPN6	-0.015	0.15	-10000	0	-0.43	21	21
VAV1	-0.021	0.17	-10000	0	-0.49	21	21
Monovalent TCR/CD3	-0.048	0.11	-10000	0	-0.32	25	25
CBL	0	0	-10000	0	-10000	0	0
LCK	-0.016	0.16	-10000	0	-0.46	22	22
PAG1	-0.014	0.15	-10000	0	-0.42	21	21
RAP1A	0	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.058	0.14	-10000	0	-0.44	25	25
CD80	-0.023	0.082	-10000	0	-0.32	18	18
CD86	-0.001	0.02	-10000	0	-0.32	1	1
PDK1/CARD11/BCL10/MALT1	-0.028	0.067	-10000	0	-0.26	12	12
HRAS	0	0	-10000	0	-10000	0	0
GO:0035030	-0.054	0.12	-10000	0	-0.42	19	19
CD8A	-0.065	0.13	-10000	0	-0.32	52	52
CD8B	-0.045	0.12	-10000	0	-0.34	34	34
PTPRC	-0.021	0.088	-10000	0	-0.36	15	15
PDK1/PKC theta	0.002	0.15	-10000	0	-0.43	16	16
CSK/PAG1	-0.01	0.15	-10000	0	-0.44	15	15
SOS1	0	0	-10000	0	-10000	0	0
peptide-MHC class I	0	0	-10000	0	-10000	0	0
GRAP2/SLP76	-0.041	0.14	-10000	0	-0.51	14	14
STIM1	0.055	0.085	-10000	0	-10000	0	0
RAS family/GTP	0.024	0.055	-10000	0	-0.17	2	2
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.018	0.14	-10000	0	-0.4	22	22
mol:DAG	-0.012	0.12	-10000	0	-0.34	17	17
RAP1A/GDP	0.009	0.018	-10000	0	-10000	0	0
PLCG1	0	0	-10000	0	-10000	0	0
CD247	-0.028	0.092	-10000	0	-0.33	22	22
cytotoxic T cell degranulation	-0.016	0.13	-10000	0	-0.54	2	2
RAP1A/GTP	-0.003	0.011	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.003	0.14	-10000	0	-0.4	19	19
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.012	0.19	0.28	58	-0.5	14	72
NRAS	0	0	-10000	0	-10000	0	0
ZAP70	-0.046	0.11	-10000	0	-0.32	37	37
GRB2/SOS1	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.04	0.14	-10000	0	-0.47	18	18
MALT1	0	0	-10000	0	-10000	0	0
TRAF6	0	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.071	0.14	-10000	0	-0.42	32	32
CARD11	-0.024	0.084	-10000	0	-0.32	19	19
PRKCB	-0.017	0.084	-10000	0	-0.3	10	10
PRKCE	-0.014	0.076	-10000	0	-0.25	11	11
PRKCQ	-0.008	0.16	-10000	0	-0.48	18	18
LCP2	-0.004	0.034	-10000	0	-10000	0	0
BCL10	0	0	-10000	0	-10000	0	0
regulation of survival gene product expression	0.006	0.11	-10000	0	-0.3	16	16
IKK complex	0.027	0.045	-10000	0	-0.11	4	4
RAS family/GDP	-0.002	0.005	-10000	0	-10000	0	0
MAP3K14	0.014	0.08	-10000	0	-0.25	5	5
PDPK1	0.006	0.12	-10000	0	-0.34	13	13
TCR/CD3/MHC I/CD8/Fyn	-0.029	0.17	-10000	0	-0.51	16	16

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.13	0.43	-9999	-1.2	26	26
IL23A	-0.1	0.36	-9999	-1.1	19	19
NF kappa B1 p50/RelA/I kappa B alpha	-0.17	0.29	-9999	-0.92	25	25
positive regulation of T cell mediated cytotoxicity	-0.12	0.38	-9999	-0.99	28	28
ITGA3	-0.12	0.4	-9999	-1.1	27	27
IL17F	-0.052	0.24	-9999	-0.65	20	20
IL12B	-0.005	0.077	-9999	-0.33	13	13
STAT1 (dimer)	-0.18	0.31	-9999	-0.95	28	28
CD4	-0.096	0.33	-9999	-0.92	23	23
IL23	-0.15	0.32	-9999	-1	19	19
IL23R	-0.007	0.076	-9999	-10000	0	0
IL1B	-0.12	0.4	-9999	-1.2	23	23
T-helper cell lineage commitment	0	0	-9999	-10000	0	0
IL24	-0.1	0.33	-9999	-0.97	19	19
TYK2	0.009	0.015	-9999	-10000	0	0
STAT4	-0.01	0.056	-9999	-0.32	8	8
STAT3	0	0	-9999	-10000	0	0
IL18RAP	-0.01	0.057	-9999	-0.33	8	8
IL12RB1	-0.018	0.094	-9999	-0.33	21	21
PIK3CA	0	0	-9999	-10000	0	0
IL12Rbeta1/TYK2	-0.016	0.065	-9999	-10000	0	0
IL23R/JAK2	-0.004	0.092	-9999	-10000	0	0
positive regulation of chronic inflammatory response	-0.12	0.38	-9999	-0.99	28	28
natural killer cell activation	0.002	0.007	-9999	-10000	0	0
JAK2	0.014	0.026	-9999	-0.31	1	1
PIK3R1	-0.004	0.053	-9999	-0.56	2	2
NFKB1	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.13	0.31	-9999	-0.98	19	19
ALOX12B	-0.098	0.33	-9999	-0.97	19	19
CXCL1	-0.24	0.56	-9999	-1.3	53	53
T cell proliferation	-0.12	0.38	-9999	-0.99	28	28
NFKBIA	0	0	-9999	-10000	0	0
IL17A	-0.029	0.2	-9999	-0.53	14	14
PI3K	-0.17	0.3	-9999	-0.92	28	28
IFNG	-0.009	0.031	-9999	-0.091	4	4
STAT3 (dimer)	-0.16	0.28	-9999	-0.9	25	25
IL18R1	-0.022	0.13	-9999	-0.79	7	7
IL23/IL23R/JAK2/TYK2/SOCS3	-0.042	0.2	-9999	-0.53	14	14
IL18/IL18R	-0.046	0.15	-9999	-0.55	19	19
macrophage activation	-0.01	0.014	-9999	-0.041	26	26
TNF	-0.1	0.35	-9999	-0.98	23	23
STAT3/STAT4	-0.18	0.3	-9999	-0.91	28	28
STAT4 (dimer)	-0.18	0.31	-9999	-0.95	28	28
IL18	-0.04	0.17	-9999	-0.79	13	13
IL19	-0.098	0.33	-9999	-0.94	21	21
STAT5A (dimer)	-0.18	0.31	-9999	-0.95	28	28
STAT1	-0.001	0.02	-9999	-0.32	1	1
SOCS3	0	0	-9999	-10000	0	0
CXCL9	-0.12	0.35	-9999	-1	19	19
MPO	-0.1	0.33	-9999	-0.9	26	26
positive regulation of humoral immune response	-0.12	0.38	-9999	-0.99	28	28
IL23/IL23R/JAK2/TYK2	-0.12	0.4	-9999	-1	28	28
IL6	-0.17	0.49	-9999	-1.4	31	31
STAT5A	0	0	-9999	-10000	0	0
IL2	-0.002	0.008	-9999	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0.002	0.007	-9999	-10000	0	0
CD3E	-0.12	0.37	-9999	-1.1	22	22
keratinocyte proliferation	-0.12	0.38	-9999	-0.99	28	28
NOS2	-0.1	0.35	-9999	-1	21	21

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.056	0.11	-9999	-0.51	8	8
EFNA5	-0.027	0.14	-9999	-0.62	11	11
FYN	-0.049	0.097	-9999	-0.46	8	8
neuron projection morphogenesis	-0.056	0.11	-9999	-0.51	8	8
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.056	0.11	-9999	-0.51	8	8
EPHA5	-0.072	0.13	-9999	-0.32	58	58

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.017	0.092	-9999	-0.53	8	8
ARNO/beta Arrestin1-2	-0.007	0.024	-9999	-10000	0	0
EGFR	-0.006	0.057	-9999	-0.48	3	3
EPHA2	0	0	-9999	-10000	0	0
USP6	-0.002	0.028	-9999	-0.32	2	2
IQSEC1	0	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.24	0.3	-9999	-0.61	103	103
ARRB2	-0.004	0.018	-9999	-10000	0	0
mol:GTP	0.009	0.031	-9999	-0.16	8	8
ARRB1	0	0	-9999	-10000	0	0
FBXO8	0	0	-9999	-10000	0	0
TSHR	-0.034	0.098	-9999	-0.32	27	27
EGF	-0.32	0.39	-9999	-0.8	102	102
somatostatin receptor activity	0	0	-9999	-0.001	28	28
ARAP2	-0.003	0.049	-9999	-0.8	1	1
mol:GDP	-0.042	0.088	-9999	-0.27	20	20
mol:PI-3-4-5-P3	0	0	-9999	-0.001	23	23
ITGA2B	-0.007	0.048	-9999	-0.32	6	6
ARF6	0	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0	0	-9999	-10000	0	0
ADAP1	-0.025	0.14	-9999	-0.8	8	8
KIF13B	0	0	-9999	-10000	0	0
HGF/MET	-0.038	0.14	-9999	-0.61	15	15
PXN	0	0	-9999	-10000	0	0
ARF6/GTP	-0.056	0.11	-9999	-0.29	26	26
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.21	0.26	-9999	-0.53	103	103
ADRB2	-0.014	0.065	-9999	-0.32	11	11
receptor agonist activity	0	0	-9999	0	28	28
actin filament binding	0	0	-9999	-0.001	30	30
SRC	0	0	-9999	-10000	0	0
ITGB3	-0.015	0.11	-9999	-0.8	5	5
GNAQ	0	0	-9999	-10000	0	0
EFA6/PI-4-5-P2	0	0	-9999	-0.001	27	27
ARF6/GDP	0.012	0.046	-9999	-0.28	1	1
ARF6/GDP/GULP/ACAP1	-0.065	0.13	-9999	-0.54	13	13
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.013	0.073	-9999	-0.51	5	5
ACAP1	-0.024	0.084	-9999	-0.32	19	19
ACAP2	0	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	-0.005	0.027	-9999	-10000	0	0
EFNA1	0	0	-9999	-10000	0	0
HGF	-0.038	0.16	-9999	-0.7	14	14
CYTH3	0.009	0.002	-9999	-10000	0	0
CYTH2	0.005	0.002	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	0	18	18
endosomal lumen acidification	0	0	-9999	-0.001	30	30
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.034	0.16	-9999	-0.8	11	11
GNAQ/ARNO	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	15	15
MET	-0.012	0.098	-9999	-0.8	4	4
GNA14	-0.049	0.19	-9999	-0.8	16	16
GNA15	-0.006	0.044	-9999	-0.32	5	5
GIT1	0	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	27	27
GNA11	-0.003	0.049	-9999	-0.8	1	1
LHCGR	-0.013	0.062	-9999	-0.32	10	10
AGTR1	-0.14	0.3	-9999	-0.8	44	44
desensitization of G-protein coupled receptor protein signaling pathway	-0.005	0.027	-9999	-10000	0	0
IPCEF1/ARNO	-0.17	0.21	-9999	-0.42	103	103
alphaIIb/beta3 Integrin	-0.016	0.093	-9999	-0.64	5	5

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0	0	-9999	-10000	0	0
LAT2	-0.077	0.14	-9999	-0.43	21	21
AP1	-0.081	0.15	-9999	-0.52	14	14
mol:PIP3	-0.066	0.2	-9999	-0.64	10	10
IKBKB	-0.023	0.12	-9999	-0.32	10	10
AKT1	-0.094	0.17	-9999	-0.67	9	9
IKBKG	-0.023	0.12	-9999	-0.32	10	10
MS4A2	-0.072	0.22	-9999	-0.7	26	26
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
MAP3K1	-0.022	0.13	-9999	-0.45	9	9
mol:Ca2+	-0.045	0.16	-9999	-0.36	23	23
LYN	0	0	-9999	-10000	0	0
CBLB	-0.073	0.14	-9999	-0.42	21	21
SHC1	0	0	-9999	-10000	0	0
RasGAP/p62DOK	0	0	-9999	-10000	0	0
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	-0.005	0.04	-9999	-0.32	4	4
PLD2	-0.12	0.21	-9999	-0.48	59	59
PTPN13	-0.063	0.18	-9999	-0.51	22	22
PTPN11	0	0.003	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.019	0.14	-9999	-0.41	9	9
SYK	-0.007	0.073	-9999	-0.64	3	3
GRB2	0	0	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.11	0.19	-9999	-0.51	23	23
LAT	-0.078	0.14	-9999	-0.42	23	23
PAK2	-0.032	0.14	-9999	-0.51	9	9
NFATC2	-0.044	0.069	-9999	-10000	0	0
HRAS	-0.042	0.15	-9999	-0.54	10	10
GAB2	-0.001	0.02	-9999	-0.32	1	1
PLA2G1B	0.026	0.02	-9999	-10000	0	0
Fc epsilon R1	-0.14	0.26	-9999	-0.59	59	59
Antigen/IgE/Fc epsilon R1	-0.13	0.24	-9999	-0.54	59	59
mol:GDP	-0.049	0.16	-9999	-0.56	10	10
JUN	-0.002	0.028	-9999	-0.32	2	2
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	-0.004	0.054	-9999	-0.56	2	2
FOS	-0.049	0.19	-9999	-0.8	16	16
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.079	0.15	-9999	-0.43	23	23
CHUK	-0.023	0.12	-9999	-0.32	10	10
KLRG1	-0.075	0.14	-9999	-0.39	23	23
VAV1	-0.084	0.14	-9999	-0.43	23	23
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.073	0.14	-9999	-0.42	21	21
negative regulation of mast cell degranulation	-0.07	0.13	-9999	-0.47	12	12
BTK	-0.072	0.14	-9999	-0.43	21	21
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.11	0.22	-9999	-0.43	62	62
GAB2/PI3K/SHP2	-0.1	0.19	-9999	-0.75	9	9
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.083	0.16	-9999	-0.36	48	48
RAF1	0.016	0.024	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.13	0.24	-9999	-0.52	62	62
FCER1G	-0.006	0.054	-9999	-0.32	7	7
FCER1A	-0.14	0.31	-9999	-0.81	46	46
Antigen/IgE/Fc epsilon R1/Fyn	-0.12	0.22	-9999	-0.51	59	59
MAPK3	0.025	0.02	-9999	-10000	0	0
MAPK1	0.025	0.02	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
MAPK8	0	0.06	-9999	-0.63	1	1
DUSP1	0	0	-9999	-10000	0	0
NF-kappa-B/RelA	-0.033	0.056	-9999	-10000	0	0
actin cytoskeleton reorganization	-0.048	0.15	-9999	-0.42	21	21
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.072	0.13	-9999	-0.56	9	9
FER	-0.073	0.14	-9999	-0.42	21	21
RELA	0	0	-9999	-10000	0	0
ITK	-0.023	0.035	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
PLCG1	-0.048	0.16	-9999	-0.43	23	23
cytokine secretion	-0.024	0.041	-9999	-10000	0	0
SPHK1	-0.11	0.16	-9999	-0.43	38	38
PTK2	-0.05	0.16	-9999	-0.44	21	21
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.11	0.19	-9999	-0.54	22	22
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.06	0.2	-9999	-0.48	23	23
MAP2K2	0.022	0.021	-9999	-10000	0	0
MAP2K1	0.022	0.021	-9999	-10000	0	0
MAP2K7	0	0	-9999	-10000	0	0
KLRG1/SHP2	-0.071	0.13	-9999	-0.49	10	10
MAP2K4	0.011	0.009	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.14	0.26	-9999	-0.56	62	62
mol:Choline	-0.11	0.21	-9999	-0.47	59	59
SHC/Grb2/SOS1	-0.066	0.13	-9999	-0.54	8	8
FYN	-0.001	0.02	-9999	-0.32	1	1
DOK1	0	0	-9999	-10000	0	0
PXN	-0.04	0.15	-9999	-0.54	8	8
HCLS1	-0.076	0.14	-9999	-0.42	21	21
PRKCB	-0.044	0.16	-9999	-0.45	11	11
FCGR2B	-0.021	0.12	-9999	-0.68	8	8
IGHE	-0.002	0.006	-9999	-10000	0	0
KLRG1/SHIP	-0.072	0.13	-9999	-0.48	12	12
LCP2	-0.004	0.034	-9999	-10000	0	0
PLA2G4A	-0.095	0.18	-9999	-0.5	31	31
RASA1	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.11	0.21	-9999	-0.47	59	59
IKK complex	-0.003	0.092	-9999	-0.23	9	9
WIPF1	0	0	-9999	-10000	0	0

×

PDGFR-alpha signaling pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.077	0.23	-9999	-0.7	28	28
PDGF/PDGFRA/CRKL	-0.056	0.17	-9999	-0.6	22	22
positive regulation of JUN kinase activity	-0.042	0.13	-9999	-0.46	22	22
CRKL	0	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.071	0.17	-9999	-0.6	22	22
AP1	-0.11	0.3	-9999	-1.2	16	16
mol:IP3	-0.041	0.18	-9999	-0.62	22	22
PLCG1	-0.041	0.18	-9999	-0.62	22	22
PDGF/PDGFRA/alphaV Integrin	-0.056	0.17	-9999	-0.6	22	22
RAPGEF1	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
mol:Ca2+	-0.041	0.18	-9999	-0.61	22	22
CAV3	-0.021	0.08	-9999	-0.32	17	17
CAV1	-0.003	0.049	-9999	-0.8	1	1
SHC/Grb2/SOS1	-0.042	0.13	-9999	-0.46	22	22
PDGF/PDGFRA/Shf	-0.056	0.17	-9999	-0.6	22	22
FOS	-0.072	0.31	-9999	-1.2	16	16
JUN	-0.008	0.025	-9999	-10000	0	0
oligodendrocyte development	-0.056	0.17	-9999	-0.6	22	22
GRB2	0	0	-9999	-10000	0	0
PIK3R1	-0.004	0.053	-9999	-0.56	2	2
mol:DAG	-0.041	0.18	-9999	-0.62	22	22
PDGF/PDGFRA	-0.077	0.23	-9999	-0.7	28	28
actin cytoskeleton reorganization	-0.056	0.17	-9999	-0.6	22	22
SRF	0.006	0.013	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
PI3K	-0.05	0.15	-9999	-0.51	23	23
PDGF/PDGFRA/Crk/C3G	-0.047	0.14	-9999	-0.51	22	22
JAK1	-0.039	0.17	-9999	-0.6	22	22
ELK1/SRF	-0.042	0.13	-9999	-0.46	22	22
SHB	0	0	-9999	-10000	0	0
SHF	0	0	-9999	-10000	0	0
CSNK2A1	0.007	0.016	-9999	-10000	0	0
GO:0007205	-0.04	0.18	-9999	-0.63	22	22
SOS1	0	0	-9999	-10000	0	0
Ras protein signal transduction	-0.042	0.13	-9999	-0.46	22	22
PDGF/PDGFRA/SHB	-0.056	0.17	-9999	-0.6	22	22
PDGF/PDGFRA/Caveolin-1	-0.058	0.17	-9999	-0.6	23	23
ITGAV	0	0	-9999	-10000	0	0
ELK1	-0.029	0.16	-9999	-0.56	22	22
PIK3CA	0	0	-9999	-10000	0	0
PDGF/PDGFRA/Crk	-0.056	0.17	-9999	-0.6	22	22
JAK-STAT cascade	-0.039	0.17	-9999	-0.6	22	22
cell proliferation	-0.056	0.17	-9999	-0.6	22	22

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.003	0.26	-10000	0	-0.94	18	18
NCK1/PAK1/Dok-R	-0.032	0.11	-10000	0	-0.43	18	18
NCK1/Dok-R	-0.081	0.31	-10000	0	-1.2	18	18
PIK3CA	0.001	0.003	-10000	0	-10000	0	0
mol:beta2-estradiol	0.007	0.063	0.24	17	-10000	0	17
RELA	0	0	-10000	0	-10000	0	0
SHC1	0	0.001	-10000	0	-10000	0	0
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	0.01	0.071	0.25	16	-0.34	2	18
TNIP2	0	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.077	0.28	-10000	0	-1.1	18	18
FN1	-0.06	0.12	-10000	0	-0.32	48	48
PLD2	-0.032	0.34	-10000	0	-1.2	18	18
PTPN11	0	0	-10000	0	-10000	0	0
GRB14	-0.24	0.37	-10000	0	-0.8	78	78
ELK1	-0.012	0.3	-10000	0	-1.1	18	18
GRB7	-0.14	0.3	-10000	0	-0.79	45	45
PAK1	0	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.069	0.31	-10000	0	-1.2	18	18
CDKN1A	0.009	0.18	-10000	0	-0.6	18	18
ITGA5	-0.002	0.028	-10000	0	-0.32	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.081	0.31	-10000	0	-1.2	18	18
CRK	0	0	-10000	0	-10000	0	0
mol:NO	0.017	0.19	-10000	0	-0.68	18	18
PLG	-0.13	0.39	-10000	0	-1.4	18	18
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.064	0.23	-10000	0	-0.91	18	18
GRB2	0	0	-10000	0	-10000	0	0
PIK3R1	-0.004	0.053	-10000	0	-0.56	2	2
ANGPT2	-0.048	0.2	-10000	0	-0.74	12	12
BMX	-0.038	0.34	-10000	0	-1.2	18	18
ANGPT1	-0.064	0.37	-10000	0	-1.4	17	17
tube development	0	0.2	-10000	0	-0.68	18	18
ANGPT4	-0.017	0.072	-10000	0	-0.32	14	14
response to hypoxia	-0.001	0.019	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.21	0.38	-10000	0	-1.4	18	18
alpha5/beta1 Integrin	-0.002	0.018	-10000	0	-10000	0	0
FGF2	-0.015	0.11	-10000	0	-0.8	5	5
STAT5A (dimer)	-0.003	0.23	-10000	0	-0.78	18	18
mol:L-citrulline	0.017	0.19	-10000	0	-0.68	18	18
AGTR1	-0.14	0.3	-10000	0	-0.8	44	44
MAPK14	-0.031	0.33	-10000	0	-1.2	18	18
Tie2/SHP2	-0.034	0.18	-10000	0	-1.4	4	4
TEK	-0.038	0.2	-10000	0	-1.6	4	4
RPS6KB1	-0.001	0.25	-10000	0	-0.9	18	18
Angiotensin II/AT1	-0.1	0.23	-10000	0	-0.62	44	44
Tie2/Ang1/GRB2	-0.091	0.34	-10000	0	-1.3	18	18
MAPK3	-0.017	0.31	-10000	0	-1.1	18	18
MAPK1	-0.017	0.31	-10000	0	-1.1	18	18
Tie2/Ang1/GRB7	-0.16	0.36	-10000	0	-1.3	18	18
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	-0.034	0.34	-10000	0	-1.2	18	18
PI3K	-0.019	0.3	-10000	0	-1.1	18	18
FES	-0.03	0.32	-10000	0	-1.2	18	18
Crk/Dok-R	-0.081	0.31	-10000	0	-1.2	18	18
Tie2/Ang1/ABIN2	-0.091	0.34	-10000	0	-1.3	18	18
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.004	0.23	-10000	0	-0.83	18	18
STAT5A	0	0	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.001	0.25	-10000	0	-0.9	18	18
Tie2/Ang2	-0.022	0.27	-10000	0	-0.95	18	18
Tie2/Ang1	-0.053	0.38	-10000	0	-1.4	18	18
FOXO1	0.008	0.24	-10000	0	-0.84	18	18
ELF1	0.013	0.014	-10000	0	-10000	0	0
ELF2	-0.034	0.34	-10000	0	-1.2	18	18
mol:Choline	-0.027	0.32	-10000	0	-1.2	18	18
cell migration	-0.016	0.063	-10000	0	-0.24	18	18
FYN	-0.006	0.23	-10000	0	-0.78	18	18
DOK2	-0.014	0.065	-10000	0	-0.32	11	11
negative regulation of cell cycle	0.012	0.16	-10000	0	-0.54	18	18
ETS1	0.001	0.059	-10000	0	-10000	0	0
PXN	0.014	0.21	-10000	0	-0.73	18	18
ITGB1	0	0	-10000	0	-10000	0	0
NOS3	0.012	0.22	-10000	0	-0.78	18	18
RAC1	0	0	-10000	0	-10000	0	0
TNF	-0.01	0.087	-10000	0	-0.27	25	25
MAPKKK cascade	-0.027	0.32	-10000	0	-1.2	18	18
RASA1	0	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.089	0.34	-10000	0	-1.3	18	18
NCK1	0	0	-10000	0	-10000	0	0
vasculogenesis	0.021	0.18	-10000	0	-0.6	18	18
mol:Phosphatidic acid	-0.027	0.32	-10000	0	-1.2	18	18
mol:Angiotensin II	0.001	0.002	-10000	0	-10000	0	0
mol:NADP	0.017	0.19	-10000	0	-0.68	18	18
Rac1/GTP	-0.061	0.21	-10000	0	-0.84	18	18
MMP2	-0.049	0.35	-10000	0	-1.3	18	18

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.11	0.33	-9999	-0.94	6	6
PLK1	-0.061	0.12	-9999	-10000	0	0
BIRC5	-0.065	0.12	-9999	-10000	0	0
HSPA1B	-0.11	0.34	-9999	-0.91	8	8
MAP2K1	0.013	0.026	-9999	-10000	0	0
BRCA2	-0.14	0.36	-9999	-0.96	10	10
FOXM1	-0.13	0.37	-9999	-1	14	14
XRCC1	-0.11	0.33	-9999	-0.88	11	11
FOXM1B/p19	-0.16	0.34	-9999	-0.91	16	16
Cyclin D1/CDK4	-0.11	0.32	-9999	-0.93	7	7
CDC2	-0.12	0.35	-9999	-0.9	14	14
TGFA	-0.1	0.33	-9999	-1	9	9
SKP2	-0.11	0.34	-9999	-0.88	12	12
CCNE1	-0.04	0.11	-9999	-0.33	34	34
CKS1B	-0.11	0.33	-9999	-0.9	9	9
RB1	-0.08	0.12	-9999	-10000	0	0
FOXM1C/SP1	-0.21	0.26	-9999	-0.92	15	15
AURKB	-0.052	0.12	-9999	-10000	0	0
CENPF	-0.14	0.36	-9999	-0.95	12	12
CDK4	-0.044	0.12	-9999	-0.32	41	41
MYC	-0.094	0.31	-9999	-0.82	7	7
CHEK2	0.013	0.026	-9999	-10000	0	0
ONECUT1	-0.11	0.33	-9999	-0.87	13	13
CDKN2A	-0.24	0.14	-9999	-0.32	194	194
LAMA4	-0.11	0.34	-9999	-0.88	12	12
FOXM1B/HNF6	-0.13	0.36	-9999	-1	13	13
FOS	-0.16	0.43	-9999	-1.2	21	21
SP1	0	0.001	-9999	-10000	0	0
CDC25B	-0.11	0.33	-9999	-0.88	11	11
response to radiation	-0.001	0.027	-9999	-10000	0	0
CENPB	-0.11	0.33	-9999	-0.9	9	9
CENPA	-0.15	0.36	-9999	-0.93	13	13
NEK2	-0.13	0.36	-9999	-0.95	12	12
HIST1H2BA	-0.12	0.33	-9999	-0.89	11	11
CCNA2	-0.094	0.15	-9999	-0.33	76	76
EP300	0	0	-9999	-10000	0	0
CCNB1/CDK1	-0.13	0.36	-9999	-0.99	12	12
CCNB2	-0.14	0.36	-9999	-0.94	13	13
CCNB1	-0.12	0.35	-9999	-0.93	12	12
ETV5	-0.11	0.34	-9999	-0.88	11	11
ESR1	-0.13	0.37	-9999	-1.1	14	14
CCND1	-0.11	0.33	-9999	-0.96	7	7
GSK3A	0.014	0.02	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	-0.062	0.12	-9999	-0.36	18	18
CDK2	0.003	0.021	-9999	-0.31	1	1
G2/M transition of mitotic cell cycle	-0.002	0.033	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.2	0.26	-9999	-0.89	15	15
GAS1	-0.11	0.34	-9999	-0.94	11	11
MMP2	-0.12	0.35	-9999	-1.1	9	9
RB1/FOXM1C	-0.12	0.34	-9999	-0.92	11	11
CREBBP	0	0	-9999	-10000	0	0

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0	0	-9999	-10000	0	0
Necdin/E2F1	-0.13	0.22	-9999	-0.7	27	27
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.028	0.097	-9999	-0.45	12	12
NGF (dimer)/p75(NTR)/BEX1	-0.11	0.21	-9999	-0.55	44	44
NT-4/5 (dimer)/p75(NTR)	-0.033	0.12	-9999	-0.62	9	9
IKBKB	0	0	-9999	-10000	0	0
AKT1	-0.03	0.099	-9999	-0.44	13	13
IKBKG	0	0	-9999	-10000	0	0
BDNF	-0.014	0.1	-9999	-0.7	5	5
MGDIs/NGR/p75(NTR)/LINGO1	-0.052	0.13	-9999	-0.45	18	18
FURIN	0	0	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.036	0.12	-9999	-0.54	13	13
LINGO1	-0.006	0.044	-9999	-0.32	5	5
Sortilin/TRAF6/NRIF	0	0.006	-9999	-10000	0	0
proBDNF (dimer)	-0.014	0.1	-9999	-0.7	5	5
NTRK1	-0.03	0.13	-9999	-0.46	17	17
RTN4R	-0.042	0.11	-9999	-0.32	34	34
neuron apoptosis	0.003	0.11	-9999	-0.46	10	10
IRAK1	0	0	-9999	-10000	0	0
SHC1	-0.034	0.12	-9999	-0.52	12	12
ARHGDIA	0	0	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
Gamma Secretase	0	0.008	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.03	0.1	-9999	-0.48	12	12
MAGEH1	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.08	0.18	-9999	-0.5	37	37
Mammalian IAPs/DIABLO	-0.007	0.054	-9999	-0.48	3	3
proNGF (dimer)	-0.01	0.087	-9999	-0.68	4	4
MAGED1	0	0	-9999	-10000	0	0
APP	-0.003	0.049	-9999	-0.8	1	1
NT-4/5 (dimer)	0	0	-9999	-10000	0	0
ZNF274	0	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	-0.028	0.098	-9999	-0.45	12	12
NGF	-0.011	0.088	-9999	-0.68	4	4
cell cycle arrest	-0.003	0.12	-9999	-0.43	12	12
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.018	0.07	-9999	-0.33	12	12
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.028	0.1	-9999	-0.53	9	9
NCSTN	-0.001	0.02	-9999	-0.32	1	1
mol:GTP	-0.034	0.12	-9999	-0.52	12	12
PSENEN	0	0	-9999	-10000	0	0
mol:ceramide	-0.03	0.1	-9999	-0.47	12	12
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.044	0.1	-9999	-0.53	2	2
p75(NTR)/beta APP	-0.034	0.13	-9999	-0.66	9	9
BEX1	-0.12	0.27	-9999	-0.63	49	49
mol:GDP	-0.035	0.12	-9999	-0.53	12	12
NGF (dimer)	-0.28	0.3	-9999	-0.55	133	133
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.046	0.11	-9999	-0.51	9	9
PIK3R1	-0.004	0.053	-9999	-0.56	2	2
RAC1/GTP	-0.029	0.1	-9999	-0.46	12	12
MYD88	0	0	-9999	-10000	0	0
CHUK	0	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.034	0.12	-9999	-0.53	12	12
RHOB	-0.003	0.049	-9999	-0.8	1	1
RHOA	0	0	-9999	-10000	0	0
MAGE-G1/E2F1	-0.068	0.098	-9999	-10000	0	0
NT3 (dimer)	-0.11	0.27	-9999	-0.69	42	42
TP53	-0.028	0.096	-9999	-0.43	13	13
PRDM4	-0.03	0.1	-9999	-0.48	12	12
BDNF (dimer)	-0.48	0.37	-9999	-0.67	184	184
PIK3CA	0	0	-9999	-10000	0	0
SORT1	0	0	-9999	-10000	0	0
activation of caspase activity	-0.028	0.096	-9999	-0.44	12	12
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.03	0.1	-9999	-0.48	12	12
RHOC	0	0	-9999	-10000	0	0
XIAP	0	0	-9999	-10000	0	0
MAPK10	-0.066	0.18	-9999	-0.59	10	10
DIABLO	0	0	-9999	-10000	0	0
SMPD2	-0.03	0.1	-9999	-0.48	12	12
APH1B	0	0	-9999	-10000	0	0
APH1A	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.034	0.12	-9999	-0.53	12	12
PSEN1	0	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-9999	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.12	0.24	-9999	-0.64	40	40
MAPK8	0.025	0.11	-9999	-0.42	9	9
MAPK9	0.026	0.11	-9999	-0.42	9	9
APAF1	0	0	-9999	-10000	0	0
NTF3	-0.11	0.27	-9999	-0.69	42	42
NTF4	0	0	-9999	-10000	0	0
NDN	-0.083	0.24	-9999	-0.8	27	27
RAC1/GDP	0	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.027	0.099	-9999	-0.45	12	12
p75 CTF/Sortilin/TRAF6/NRIF	0	0	-9999	-10000	0	0
RhoA-B-C/GTP	-0.034	0.11	-9999	-0.52	12	12
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.03	0.1	-9999	-0.46	13	13
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.032	0.11	-9999	-0.49	13	13
PRKACB	0	0	-9999	-10000	0	0
proBDNF (dimer)/p75 ECD	-0.01	0.076	-9999	-0.61	4	4
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.011	0.088	-9999	-0.68	4	4
BIRC2	-0.001	0.02	-9999	-0.32	1	1
neuron projection morphogenesis	-0.018	0.15	-9999	-0.48	12	12
BAD	-0.005	0.12	-9999	-0.48	10	10
RIPK2	0	0	-9999	-10000	0	0
NGFR	-0.045	0.16	-9999	-0.51	23	23
CYCS	-0.028	0.096	-9999	-0.44	12	12
ADAM17	0	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.03	0.1	-9999	-0.48	12	12
BCL2L11	-0.005	0.12	-9999	-0.48	10	10
BDNF (dimer)/p75(NTR)	-0.043	0.14	-9999	-0.62	13	13
PI3K	-0.033	0.11	-9999	-0.48	13	13
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.03	0.1	-9999	-0.48	12	12
NDNL2	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
PRKCI	0	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)	-0.04	0.14	-9999	-0.61	12	12
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.03	0.1	-9999	-0.48	12	12
TRAF6	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
PRKCZ	-0.091	0.25	-9999	-0.78	30	30
PLG	-0.17	0.32	-9999	-0.8	54	54
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.035	0.11	-9999	-0.46	16	16
SQSTM1	0	0	-9999	-10000	0	0
NGFRAP1	0	0	-9999	-10000	0	0
CASP3	-0.004	0.12	-9999	-0.44	10	10
E2F1	-0.1	0.15	-9999	-0.32	84	84
CASP9	0	0	-9999	-10000	0	0
IKK complex	-0.047	0.11	-9999	-0.51	5	5
NGF (dimer)/TRKA	-0.029	0.11	-9999	-0.61	8	8
MMP7	-0.29	0.38	-9999	-0.79	95	95
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.028	0.097	-9999	-0.45	12	12
MMP3	-0.34	0.39	-9999	-0.77	112	112
APAF-1/Caspase 9	-0.024	0.082	-9999	-0.44	2	2

×

Endothelins

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
AKT1	-0.052	0.14	0.27	3	-0.6	8	11
PTK2B	0	0	-10000	0	-10000	0	0
mol:Ca2+	0.015	0.14	-10000	0	-0.75	4	4
EDN1	-0.049	0.16	-10000	0	-0.85	8	8
EDN3	-0.035	0.11	-10000	0	-0.34	27	27
EDN2	-0.007	0.048	-10000	0	-0.32	6	6
HRAS/GDP	-0.024	0.1	-10000	0	-0.43	4	4
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.021	0.098	-10000	0	-0.36	10	10
ADCY4	-0.064	0.15	-10000	0	-0.52	18	18
ADCY5	-0.23	0.28	-10000	0	-0.54	103	103
ADCY6	-0.064	0.15	-10000	0	-0.52	18	18
ADCY7	-0.064	0.15	-10000	0	-0.52	18	18
ADCY1	-0.079	0.15	-10000	0	-0.5	21	21
ADCY2	-0.12	0.2	-10000	0	-0.53	41	41
ADCY3	-0.065	0.15	-10000	0	-0.52	18	18
ADCY8	-0.12	0.2	-10000	0	-0.51	44	44
ADCY9	-0.064	0.15	-10000	0	-0.52	18	18
arachidonic acid secretion	0.002	0.15	-10000	0	-0.43	12	12
ETB receptor/Endothelin-1/Gq/GTP	-0.012	0.12	-10000	0	-0.36	20	20
GNAO1	-0.1	0.27	-10000	0	-0.78	34	34
HRAS	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	-0.021	0.15	0.36	7	-0.56	8	15
ETA receptor/Endothelin-1/Gs/GTP	-0.045	0.18	0.34	7	-0.55	18	25
mol:GTP	0.001	0.003	-10000	0	-10000	0	0
COL3A1	-0.087	0.18	-10000	0	-0.62	12	12
EDNRB	-0.011	0.052	-10000	0	-0.79	1	1
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.065	0.15	-10000	0	-0.6	8	8
CYSLTR1	-0.053	0.14	-10000	0	-0.58	9	9
SLC9A1	-0.021	0.076	0.19	3	-0.31	8	11
mol:GDP	0.009	0.12	-10000	0	-0.45	5	5
SLC9A3	-0.49	0.29	-10000	0	-0.6	211	211
RAF1	0.002	0.13	-10000	0	-0.42	6	6
JUN	0.021	0.11	-10000	0	-10000	0	0
JAK2	-0.052	0.14	0.27	3	-0.6	8	11
mol:IP3	-0.026	0.11	-10000	0	-0.42	10	10
ETA receptor/Endothelin-1	-0.037	0.19	0.43	7	-0.61	11	18
PLCB1	0	0	-10000	0	-10000	0	0
PLCB2	-0.005	0.04	-10000	0	-0.32	4	4
ETA receptor/Endothelin-3	-0.033	0.091	-10000	0	-0.36	8	8
FOS	-0.023	0.26	-10000	0	-1	16	16
Gai/GDP	-0.12	0.27	-10000	0	-0.77	34	34
CRK	0	0	-10000	0	-10000	0	0
mol:Ca ++	-0.024	0.17	-10000	0	-0.6	11	11
BCAR1	0	0	-10000	0	-10000	0	0
PRKCB1	-0.003	0.12	-10000	0	-0.4	10	10
GNAQ	0	0.002	-10000	0	-10000	0	0
GNAZ	-0.052	0.2	-10000	0	-0.8	17	17
GNAL	-0.041	0.17	-10000	0	-0.7	15	15
Gs family/GDP	-0.054	0.12	-10000	0	-0.46	15	15
ETA receptor/Endothelin-1/Gq/GTP	-0.027	0.12	-10000	0	-0.4	14	14
MAPK14	0.008	0.094	-10000	0	-0.42	3	3
TRPC6	0.014	0.15	-10000	0	-0.81	4	4
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.012	0.098	-10000	0	-0.8	4	4
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.018	0.093	-10000	0	-0.37	7	7
ETB receptor/Endothelin-2	-0.011	0.049	-10000	0	-0.6	1	1
ETB receptor/Endothelin-3	-0.03	0.087	-10000	0	-0.69	2	2
ETB receptor/Endothelin-1	-0.04	0.14	-10000	0	-0.66	9	9
MAPK3	-0.011	0.22	-10000	0	-0.74	17	17
MAPK1	-0.011	0.22	-10000	0	-0.74	17	17
Rac1/GDP	-0.034	0.093	0.2	1	-0.41	5	6
cAMP biosynthetic process	-0.13	0.2	-10000	0	-0.54	29	29
MAPK8	0.014	0.12	-10000	0	-0.48	5	5
SRC	0	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.066	0.16	-10000	0	-0.4	34	34
p130Cas/CRK/Src/PYK2	0.024	0.12	-10000	0	-0.48	2	2
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.034	0.093	-10000	0	-0.41	5	5
COL1A2	-0.078	0.19	-10000	0	-0.74	10	10
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.015	0.06	-10000	0	-0.38	1	1
mol:DAG	-0.026	0.11	-10000	0	-0.42	10	10
MAP2K2	0	0.17	-10000	0	-0.5	18	18
MAP2K1	0	0.17	-10000	0	-0.5	18	18
EDNRA	-0.023	0.078	0.23	3	-0.29	2	5
positive regulation of muscle contraction	-0.039	0.12	-10000	0	-0.53	8	8
Gq family/GDP	-0.039	0.13	-10000	0	-0.5	15	15
HRAS/GTP	0.001	0.12	-10000	0	-0.4	8	8
PRKCH	0.003	0.12	-10000	0	-0.46	5	5
RAC1	0	0	-10000	0	-10000	0	0
PRKCA	0	0.12	-10000	0	-0.44	7	7
PRKCB	-0.003	0.12	-10000	0	-0.48	6	6
PRKCE	0.003	0.12	-10000	0	-0.4	9	9
PRKCD	0.003	0.12	-10000	0	-0.46	5	5
PRKCG	-0.006	0.12	-10000	0	-0.4	10	10
regulation of vascular smooth muscle contraction	-0.031	0.3	-10000	0	-1.1	16	16
PRKCQ	-0.012	0.14	-10000	0	-0.44	12	12
PLA2G4A	-0.001	0.16	-10000	0	-0.46	12	12
GNA14	-0.049	0.19	-10000	0	-0.8	16	16
GNA15	-0.006	0.044	-10000	0	-0.32	5	5
GNA12	0	0	-10000	0	-10000	0	0
GNA11	-0.003	0.049	-10000	0	-0.8	1	1
Rac1/GTP	-0.021	0.15	0.36	7	-0.56	8	15
MMP1	-0.051	0.21	-10000	0	-1.1	7	7

×

Syndecan-4-mediated 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.009	0.04	-9999	-10000	0	0
Syndecan-4/Syndesmos	-0.11	0.17	-9999	-0.68	10	10
positive regulation of JNK cascade	-0.11	0.17	-9999	-0.62	15	15
Syndecan-4/ADAM12	-0.18	0.19	-9999	-0.61	24	24
CCL5	-0.052	0.12	-9999	-0.32	42	42
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0	0	-9999	-10000	0	0
ITGA5	-0.002	0.028	-9999	-0.32	2	2
SDCBP	0	0	-9999	-10000	0	0
PLG	-0.16	0.32	-9999	-0.78	54	54
ADAM12	-0.16	0.16	-9999	-0.32	130	130
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.055	0.048	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.13	0.19	-9999	-0.67	15	15
Syndecan-4/CXCL12/CXCR4	-0.12	0.18	-9999	-0.66	15	15
Syndecan-4/Laminin alpha3	-0.13	0.18	-9999	-0.67	13	13
MDK	-0.044	0.11	-9999	-0.32	35	35
Syndecan-4/FZD7	-0.11	0.17	-9999	-0.68	10	10
Syndecan-4/Midkine	-0.13	0.18	-9999	-0.63	14	14
FZD7	-0.003	0.049	-9999	-0.8	1	1
Syndecan-4/FGFR1/FGF	-0.11	0.17	-9999	-0.62	11	11
THBS1	-0.006	0.07	-9999	-0.8	2	2
integrin-mediated signaling pathway	-0.14	0.18	-9999	-0.59	19	19
positive regulation of MAPKKK cascade	-0.11	0.17	-9999	-0.62	15	15
Syndecan-4/TACI	-0.1	0.18	-9999	-0.69	10	10
CXCR4	-0.017	0.073	-9999	-0.32	14	14
cell adhesion	-0.014	0.04	-9999	-0.38	2	2
Syndecan-4/Dynamin	-0.11	0.17	-9999	-0.68	10	10
Syndecan-4/TSP1	-0.11	0.18	-9999	-0.72	10	10
Syndecan-4/GIPC	-0.11	0.17	-9999	-0.68	10	10
Syndecan-4/RANTES	-0.13	0.18	-9999	-0.61	16	16
ITGB1	0	0	-9999	-10000	0	0
LAMA1	-0.035	0.14	-9999	-0.47	19	19
LAMA3	-0.035	0.12	-9999	-0.38	24	24
RAC1	0	0	-9999	-10000	0	0
PRKCA	0.036	0.08	-9999	-0.71	2	2
Syndecan-4/alpha-Actinin	-0.11	0.17	-9999	-0.68	10	10
TFPI	-0.037	0.17	-9999	-0.8	12	12
F2	-0.002	0.027	-9999	-0.3	2	2
alpha5/beta1 Integrin	-0.002	0.018	-9999	-10000	0	0
positive regulation of cell adhesion	-0.13	0.19	-9999	-0.65	18	18
ACTN1	0	0	-9999	-10000	0	0
TNC	-0.089	0.16	-9999	-0.35	66	66
Syndecan-4/CXCL12	-0.12	0.19	-9999	-0.69	14	14
FGF6	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
CXCL12	-0.017	0.11	-9999	-0.72	6	6
TNFRSF13B	0	0	-9999	-10000	0	0
FGF2	-0.015	0.11	-9999	-0.8	5	5
FGFR1	0	0	-9999	-10000	0	0
Syndecan-4/PI-4-5-P2	-0.1	0.18	-9999	-0.69	10	10
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.056	0.13	-9999	-0.32	47	47
cell migration	-0.02	0.019	-9999	-10000	0	0
PRKCD	0.004	0.008	-9999	-10000	0	0
vasculogenesis	-0.11	0.17	-9999	-0.68	10	10
SDC4	-0.11	0.19	-9999	-0.73	10	10
Syndecan-4/Tenascin C	-0.15	0.19	-9999	-0.62	19	19
Syndecan-4/PI-4-5-P2/PKC alpha	-0.044	0.038	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.11	0.17	-9999	-0.68	10	10
MMP9	-0.13	0.16	-9999	-0.32	105	105
Rac1/GTP	-0.014	0.041	-9999	-0.39	2	2
cytoskeleton organization	-0.11	0.17	-9999	-0.65	10	10
GIPC1	0	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.13	0.19	-9999	-0.68	15	15

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.059	0.13	0.34	34	-10000	0	34
GNAI2	0	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.009	0.038	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.1	0.27	-10000	0	-0.78	34	34
RhoA/GTP	-0.06	0.13	-10000	0	-0.35	34	34
negative regulation of cAMP metabolic process	-0.067	0.14	-10000	0	-0.39	34	34
GNAZ	-0.052	0.2	-10000	0	-0.8	17	17
GNAI3	0	0	-10000	0	-10000	0	0
GNA12	0	0	-10000	0	-10000	0	0
S1PR5	-0.016	0.07	-10000	0	-0.32	13	13
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.068	0.15	-10000	0	-0.39	34	34
RhoA/GDP	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
GNAI1	-0.012	0.098	-10000	0	-0.8	4	4

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.003	0.037	-9999	-0.22	7	7
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.016	0.056	-9999	-10000	0	0
STXBP1	0	0	-9999	-10000	0	0
ACh/CHRNA1	-0.068	0.087	-9999	-0.19	84	84
RAB3GAP2/RIMS1/UNC13B	-0.013	0.044	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
UniProt:P30996	0	0	-9999	-10000	0	0
UniProt:Q60393	0	0	-9999	-10000	0	0
CST086	0	0	-9999	-10000	0	0
RIMS1	-0.025	0.086	-9999	-0.32	20	20
mol:ACh	-0.006	0.03	-9999	-0.16	6	6
RAB3GAP2	0	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.018	0.047	-9999	-0.32	2	2
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.068	0.087	-9999	-0.19	84	84
UNC13B	0	0	-9999	-10000	0	0
CHRNA1	-0.1	0.15	-9999	-0.32	84	84
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.032	0.1	-9999	-0.44	11	11
SNAP25	-0.026	0.063	-9999	-0.38	6	6
VAMP2	0	0	-9999	-10000	0	0
SYT1	-0.039	0.15	-9999	-0.48	21	21
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.005	0.028	-9999	-10000	0	0
STX1A/SNAP25 fragment 1/VAMP2	-0.018	0.047	-9999	-0.32	2	2

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	-0.003	0.021	-9999	-10000	0	0
RGS9BP	-0.096	0.26	-9999	-0.8	31	31
mol:GTP	0	0	-9999	-10000	0	0
GRK1	-0.007	0.048	-9999	-0.32	6	6
mol:Na +	-0.022	0.058	-9999	-10000	0	0
mol:ADP	-0.002	0.034	-9999	-10000	0	0
GNAT2	0	0	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.14	0.25	-9999	-0.56	65	65
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0	0	-9999	-10000	0	0
GRK7	0	0	-9999	-10000	0	0
CNGB3	-0.016	0.07	-9999	-0.32	13	13
Cone Metarhodopsin II/X-Arrestin	0	0	-9999	-10000	0	0
mol:Ca2+	-0.031	0.07	-9999	-0.31	6	6
Cone PDE6	-0.12	0.22	-9999	-0.48	65	65
Cone Metarhodopsin II	-0.004	0.024	-9999	-10000	0	0
Na + (4 Units)	-0.031	0.07	-9999	-0.31	6	6
GNAT2/GDP	-0.12	0.22	-9999	-0.48	65	65
GNB5	0	0	-9999	-10000	0	0
mol:GMP (4 units)	0	0	-9999	-10000	0	0
Cone Transducin	-0.003	0.022	-9999	-10000	0	0
SLC24A2	-0.025	0.086	-9999	-0.32	20	20
GNB3/GNGT2	-0.005	0.031	-9999	-10000	0	0
GNB3	0	0	-9999	-10000	0	0
GNAT2/GTP	0	0	-9999	-10000	0	0
CNGA3	-0.024	0.084	-9999	-0.32	19	19
ARR3	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.022	0.058	-9999	-10000	0	0
mol:Pi	-0.14	0.25	-9999	-0.55	65	65
Cone CNG Channel	-0.017	0.045	-9999	-10000	0	0
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.025	0.086	-9999	-0.32	20	20
RGS9	-0.12	0.28	-9999	-0.8	38	38
PDE6C	0	0	-9999	-10000	0	0
GNGT2	-0.007	0.048	-9999	-0.32	6	6
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0	0	-9999	-10000	0	0

×

Calcium signaling in the CD4+ TCR pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.014	0.022	-9999	-10000	0	0
NFATC2	-0.033	0.061	-9999	-0.26	5	5
NFATC3	-0.014	0.02	-9999	-10000	0	0
CD40LG	-0.17	0.22	-9999	-0.64	29	29
PTGS2	-0.24	0.32	-9999	-0.78	59	59
JUNB	0	0	-9999	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.009	0.013	-9999	-10000	0	0
CaM/Ca2+	-0.009	0.013	-9999	-10000	0	0
CALM1	-0.002	0.004	-9999	-10000	0	0
JUN	-0.004	0.029	-9999	-0.33	2	2
mol:Ca2+	-0.01	0.012	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	-0.001	0.002	-9999	-10000	0	0
FOSL1	-0.032	0.1	-9999	-0.34	24	24
CREM	0	0	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.085	0.12	-9999	-0.48	6	6
FOS	-0.051	0.19	-9999	-0.8	16	16
IFNG	-0.2	0.24	-9999	-0.62	44	44
AP-1/NFAT1-c-4	-0.2	0.25	-9999	-0.75	27	27
FASLG	-0.19	0.23	-9999	-0.63	38	38
NFAT1-c-4/ICER1	-0.05	0.071	-9999	-10000	0	0
IL2RA	-0.2	0.24	-9999	-0.65	41	41
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	-0.17	0.21	-9999	-0.63	27	27
JunB/Fra1/NFAT1-c-4	-0.053	0.082	-9999	-0.39	1	1
IL4	-0.17	0.21	-9999	-0.62	26	26
IL2	-0.01	0.013	-9999	-10000	0	0
IL3	-0.018	0.022	-9999	-10000	0	0
FKBP1A	0	0	-9999	-10000	0	0
BATF3	-0.004	0.053	-9999	-0.56	2	2
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	-0.001	0.02	-9999	-0.32	1	1

×

Nongenotropic Androgen 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
PTK2	0.009	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.034	0.1	-10000	0	-0.48	10	10
regulation of S phase of mitotic cell cycle	-0.019	0.068	-10000	0	-0.33	11	11
GNAO1	-0.1	0.27	-10000	0	-0.78	34	34
HRAS	0	0	-10000	0	-10000	0	0
SHBG/T-DHT	-0.029	0.12	-10000	0	-0.54	14	14
PELP1	0	0	-10000	0	-10000	0	0
AKT1	0.009	0	-10000	0	-10000	0	0
MAP2K1	0.008	0.092	-10000	0	-0.38	10	10
T-DHT/AR	-0.042	0.13	-10000	0	-0.35	31	31
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	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.012	0.098	-10000	0	-0.8	4	4
mol:GDP	-0.03	0.12	-10000	0	-0.57	11	11
cell proliferation	0.002	0.13	-10000	0	-0.38	18	18
PIK3CA	0	0	-10000	0	-10000	0	0
FOS	-0.023	0.22	-10000	0	-0.87	16	16
mol:Ca2+	-0.018	0.032	-10000	0	-0.08	47	47
MAPK3	0.006	0.11	-10000	0	-0.36	12	12
MAPK1	0.006	0.064	-10000	0	-0.23	2	2
PIK3R1	-0.004	0.053	-10000	0	-0.56	2	2
mol:IP3	0	0.001	-10000	0	-0.005	16	16
cAMP biosynthetic process	-0.013	0.12	-10000	0	-0.51	14	14
GNG2	-0.007	0.048	-10000	0	-0.32	6	6
potassium channel inhibitor activity	0	0.001	-10000	0	-0.005	16	16
HRAS/GTP	-0.029	0.088	-10000	0	-0.43	10	10
actin cytoskeleton reorganization	-0.002	0.028	-10000	0	-0.43	1	1
SRC	0	0	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.005	16	16
PI3K	-0.003	0.035	-10000	0	-0.53	1	1
apoptosis	-0.001	0.12	0.41	16	-10000	0	16
T-DHT/AR/PELP1	-0.035	0.11	-10000	0	-0.53	10	10
HRAS/GDP	-0.028	0.11	-10000	0	-0.56	10	10
CREB1	0	0.13	-10000	0	-0.44	16	16
RAC1-CDC42/GTP	-0.002	0.028	-10000	0	-0.44	1	1
AR	-0.057	0.17	-10000	0	-0.47	31	31
GNB1	0	0	-10000	0	-10000	0	0
RAF1	-0.028	0.083	-10000	0	-0.4	10	10
RAC1-CDC42/GDP	-0.026	0.1	-10000	0	-0.54	10	10
T-DHT/AR/PELP1/Src	-0.031	0.1	-10000	0	-0.48	10	10
MAP2K2	0.008	0.092	-10000	0	-0.38	10	10
T-DHT/AR/PELP1/Src/PI3K	-0.019	0.068	-10000	0	-0.33	11	11
GNAZ	-0.052	0.2	-10000	0	-0.8	17	17
SHBG	-0.043	0.18	-10000	0	-0.8	14	14
Gi family/GNB1/GNG2/GDP	-0.076	0.17	-10000	0	-0.47	34	34
mol:T-DHT	0	0.001	-10000	0	-0.003	14	14
RAC1	0	0	-10000	0	-10000	0	0
GNRH1	0.003	0.037	-10000	0	-0.22	7	7
Gi family/GTP	-0.069	0.14	-10000	0	-0.33	47	47
CDC42	0	0	-10000	0	-10000	0	0

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.15	0.31	-9999	-0.78	51	51
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0	0	-9999	-10000	0	0
TCEB1	0	0	-9999	-10000	0	0
HIF1A/p53	-0.014	0.034	-9999	-10000	0	0
HIF1A	-0.016	0.038	-9999	-10000	0	0
COPS5	0	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0	0	-9999	-10000	0	0
FIH (dimer)	0	0	-9999	-10000	0	0
CDKN2A	-0.24	0.14	-9999	-0.32	194	194
ARNT/IPAS	-0.12	0.24	-9999	-0.61	49	49
HIF1AN	0	0	-9999	-10000	0	0
GNB2L1	-0.001	0.02	-9999	-0.32	1	1
HIF1A/ARNT	-0.014	0.034	-9999	-10000	0	0
CUL2	0	0	-9999	-10000	0	0
OS9	-0.021	0.08	-9999	-0.32	17	17
RACK1/Elongin B/Elongin C	-0.001	0.01	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	-0.014	0.034	-9999	-10000	0	0
PHD1-3/OS9	-0.068	0.16	-9999	-0.48	32	32
HIF1A/RACK1/Elongin B/Elongin C	-0.011	0.029	-9999	-10000	0	0
VHL	0	0	-9999	-10000	0	0
HSP90AA1	0	0	-9999	-10000	0	0
HIF1A/JAB1	-0.014	0.034	-9999	-10000	0	0
EGLN3	-0.099	0.26	-9999	-0.8	32	32
EGLN2	0	0	-9999	-10000	0	0
EGLN1	0	0	-9999	-10000	0	0
TP53	0	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0	0.001	-9999	-10000	0	0
ARNT	0	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.11	0.069	-9999	-0.54	1	1

×

Class IB PI3K non-lipid kinase 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
cAMP biosynthetic process	0.034	0.16	0.79	11	-10000	0	11
PI3K Class IB/PDE3B	-0.034	0.16	-10000	0	-0.8	11	11
PDE3B	-0.034	0.16	-10000	0	-0.8	11	11

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.1	0.27	-9999	-0.78	34	34
CDC42/GTP	-0.059	0.13	-9999	-0.35	34	34
PLCG1	-0.061	0.14	-9999	-0.36	34	34
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0	0	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
cell migration	-0.058	0.13	-9999	-0.34	34	34
S1PR5	-0.016	0.07	-9999	-0.32	13	13
S1PR4	-0.006	0.044	-9999	-0.32	5	5
MAPK3	-0.061	0.14	-9999	-0.59	7	7
MAPK1	-0.061	0.14	-9999	-0.36	34	34
S1P/S1P5/Gi	-0.068	0.15	-9999	-0.39	34	34
GNAI1	-0.012	0.098	-9999	-0.8	4	4
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.009	0.038	-9999	-10000	0	0
RHOA	-0.002	0.018	-9999	-10000	0	0
S1P/S1P4/Gi	-0.066	0.15	-9999	-0.39	34	34
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.052	0.2	-9999	-0.8	17	17
S1P/S1P4/G12/G13	-0.003	0.02	-9999	-10000	0	0
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.043	0.074	-9999	-10000	0	0
epithelial cell differentiation	-0.074	0.12	-9999	-0.46	12	12
ITCH	0.014	0.024	-9999	-10000	0	0
WWP1	-0.04	0.068	-9999	-10000	0	0
FYN	-0.001	0.02	-9999	-0.32	1	1
EGFR	-0.006	0.057	-9999	-0.48	3	3
PRL	-0.058	0.12	-9999	-0.32	47	47
neuron projection morphogenesis	-0.043	0.14	-9999	-0.47	9	9
PTPRZ1	-0.06	0.16	-9999	-0.39	39	39
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.074	0.14	-9999	-0.53	9	9
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.093	0.17	-9999	-0.52	31	31
ADAM17	0.014	0.024	-9999	-10000	0	0
ErbB4/ErbB4	-0.053	0.09	-9999	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.046	0.079	-9999	-10000	0	0
NCOR1	0	0	-9999	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.086	0.16	-9999	-0.49	31	31
GRIN2B	-0.081	0.15	-9999	-0.47	31	31
ErbB4/ErbB2/betacellulin	-0.086	0.16	-9999	-0.5	31	31
STAT1	-0.001	0.02	-9999	-0.32	1	1
HBEGF	0	0	-9999	-10000	0	0
PRLR	-0.088	0.24	-9999	-0.65	35	35
E4ICDs/ETO2	-0.047	0.077	-9999	-10000	0	0
axon guidance	-0.011	0.084	-9999	-0.38	1	1
NEDD4	0.014	0.024	-9999	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	-0.1	0.2	-9999	-0.59	30	30
CBFA2T3	-0.007	0.048	-9999	-0.32	6	6
ErbB4/ErbB2/HBEGF	-0.043	0.095	-9999	-0.48	9	9
MAPK3	-0.068	0.13	-9999	-0.5	9	9
STAT1 (dimer)	-0.044	0.076	-9999	-10000	0	0
MAPK1	-0.068	0.13	-9999	-0.5	9	9
JAK2	-0.001	0.02	-9999	-0.32	1	1
ErbB4/ErbB2/neuregulin 1 beta	-0.1	0.18	-9999	-0.5	39	39
NRG1	-0.057	0.21	-9999	-0.61	31	31
NRG3	-0.005	0.04	-9999	-0.32	4	4
NRG2	-0.046	0.19	-9999	-0.8	15	15
NRG4	-0.007	0.048	-9999	-0.32	6	6
heart development	-0.011	0.084	-9999	-0.38	1	1
neural crest cell migration	-0.1	0.17	-9999	-0.49	39	39
ERBB2	0.004	0.12	-9999	-0.61	9	9
WWOX/E4ICDs	-0.043	0.074	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.044	0.071	-9999	-0.46	1	1
apoptosis	0.04	0.07	-9999	-10000	0	0
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.072	0.14	-9999	-0.56	15	15
ErbB4/ErbB2/epiregulin	-0.054	0.11	-9999	-0.53	9	9
ErbB4/ErbB4/betacellulin/betacellulin	-0.09	0.16	-9999	-0.54	23	23
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.098	0.15	-9999	-0.48	24	24
MDM2	-0.053	0.11	-9999	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.079	0.16	-9999	-0.49	31	31
STAT5A	-0.004	0.078	-9999	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.088	0.16	-9999	-0.48	32	32
DLG4	0	0	-9999	-10000	0	0
GRB2/SHC	0	0	-9999	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.04	0.068	-9999	-10000	0	0
STAT5A (dimer)	-0.079	0.13	-9999	-0.49	12	12
MAP3K7IP2	0	0	-9999	-10000	0	0
STAT5B (dimer)	-0.033	0.057	-9999	-10000	0	0
LRIG1	-0.003	0.049	-9999	-0.8	1	1
EREG	-0.025	0.086	-9999	-0.32	20	20
BTC	-0.075	0.23	-9999	-0.74	26	26
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.019	0.081	-9999	-0.38	1	1
ERBB4	-0.053	0.09	-9999	-10000	0	0
STAT5B	0	0	-9999	-10000	0	0
YAP1	-0.014	0.024	-9999	-10000	0	0
GRB2	0	0	-9999	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.046	0.096	-9999	-0.48	9	9
glial cell differentiation	0.039	0.067	-9999	-10000	0	0
WWOX	0	0	-9999	-10000	0	0
cell proliferation	-0.086	0.2	-9999	-0.55	20	20

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.007	0.019	-9999	-10000	0	0
VDR	-0.058	0.2	-9999	-0.75	20	20
FAM120B	0	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.016	0.062	-9999	-0.39	1	1
RXRs/LXRs/DNA/Oxysterols	-0.011	0.05	-9999	-0.36	1	1
MED1	0	0	-9999	-10000	0	0
mol:9cRA	0.005	0.004	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	-0.023	0.085	-9999	-0.33	18	18
RXRs/NUR77	-0.061	0.14	-9999	-0.47	26	26
RXRs/PPAR	-0.019	0.066	-9999	-0.32	11	11
NCOR2	0	0	-9999	-10000	0	0
VDR/VDR/Vit D3	-0.045	0.16	-9999	-0.58	20	20
RARs/VDR/DNA/Vit D3	-0.042	0.13	-9999	-0.45	23	23
RARA	0	0	-9999	-10000	0	0
NCOA1	0	0	-9999	-10000	0	0
VDR/VDR/DNA	-0.058	0.2	-9999	-0.75	20	20
RARs/RARs/DNA/9cRA	-0.01	0.064	-9999	-0.46	5	5
RARG	-0.002	0.028	-9999	-0.32	2	2
RPS6KB1	0.01	0.027	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	-0.023	0.085	-9999	-0.33	18	18
THRA	0	0	-9999	-10000	0	0
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	-0.045	0.16	-9999	-0.58	20	20
RXRs/PPAR/9cRA/PGJ2/DNA	-0.032	0.098	-9999	-0.48	10	10
NR1H4	-0.17	0.33	-9999	-0.77	58	58
RXRs/LXRs/DNA	-0.028	0.088	-9999	-0.43	10	10
NR1H2	0.013	0.004	-9999	-10000	0	0
NR1H3	0.012	0.005	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.062	0.15	-9999	-0.48	28	28
NR4A1	-0.049	0.19	-9999	-0.8	16	16
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.084	0.15	-9999	-0.34	63	63
RXRG	-0.054	0.18	-9999	-0.44	37	37
RXR alpha/CCPG	0	0	-9999	-10000	0	0
RXRA	0.012	0.004	-9999	-10000	0	0
RXRB	0.012	0.005	-9999	-10000	0	0
THRB	-0.04	0.17	-9999	-0.8	13	13
PPARG	-0.006	0.044	-9999	-0.32	5	5
PPARD	0	0	-9999	-10000	0	0
TNF	0.039	0.067	-9999	-10000	0	0
mol:Oxysterols	0.005	0.003	-9999	-10000	0	0
cholesterol transport	-0.011	0.05	-9999	-0.36	1	1
PPARA	-0.003	0.049	-9999	-0.8	1	1
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	-0.015	0.11	-9999	-0.8	5	5
RXRs/NUR77/BCL2	-0.038	0.1	-9999	-0.33	26	26
SREBF1	0.042	0.06	-9999	-10000	0	0
RXRs/RXRs/DNA/9cRA	-0.032	0.098	-9999	-0.48	10	10
ABCA1	0.042	0.06	-9999	-10000	0	0
RARs/THRs	-0.032	0.12	-9999	-0.46	18	18
RXRs/FXR	-0.13	0.22	-9999	-0.51	63	63
BCL2	0	0	-9999	-10000	0	0

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	-0.075	0.14	-10000	0	-0.41	37	37
NFATC2	0.007	0.12	-10000	0	-0.54	5	5
NFATC3	-0.002	0.054	-10000	0	-10000	0	0
CD40LG	-0.13	0.24	-10000	0	-0.9	9	9
ITCH	-0.056	0.11	-10000	0	-10000	0	0
CBLB	-0.056	0.11	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.13	0.2	-10000	0	-0.96	6	6
JUNB	0	0	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.069	0.14	-10000	0	-0.34	52	52
T cell anergy	-0.064	0.19	-10000	0	-0.45	52	52
TLE4	0.026	0.086	-10000	0	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.062	0.17	-10000	0	-0.83	5	5
AP-1/NFAT1-c-4	-0.14	0.26	-10000	0	-1	9	9
IKZF1	0.021	0.1	-10000	0	-0.49	3	3
T-helper 2 cell differentiation	-0.033	0.21	-10000	0	-0.7	15	15
AP-1/NFAT1	-0.054	0.15	-10000	0	-0.53	18	18
CALM1	-0.037	0.073	-10000	0	-10000	0	0
EGR2	0.02	0.21	-10000	0	-1.6	3	3
EGR3	0.006	0.27	-10000	0	-1.5	7	7
NFAT1/FOXP3	-0.068	0.16	-10000	0	-0.52	15	15
EGR1	-0.012	0.098	-10000	0	-0.8	4	4
JUN	-0.012	0.033	-10000	0	-0.37	1	1
EGR4	-0.006	0.045	-10000	0	-0.32	5	5
mol:Ca2+	-0.042	0.082	-10000	0	-10000	0	0
GBP3	0.026	0.086	-10000	0	-10000	0	0
FOSL1	-0.032	0.1	-10000	0	-0.34	24	24
NFAT1-c-4/MAF/IRF4	-0.047	0.17	-10000	0	-0.76	8	8
DGKA	0.026	0.086	-10000	0	-10000	0	0
CREM	0	0	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.036	0.17	-10000	0	-0.76	9	9
CTLA4	-0.068	0.2	-10000	0	-0.49	29	29
NFAT1-c-4 (dimer)/EGR1	-0.041	0.19	-10000	0	-0.86	9	9
NFAT1-c-4 (dimer)/EGR4	-0.034	0.17	-10000	0	-0.77	9	9
FOS	-0.06	0.19	-10000	0	-0.81	16	16
IFNG	-0.053	0.11	-10000	0	-10000	0	0
T cell activation	0.017	0.14	-10000	0	-0.82	1	1
MAF	0	0	-10000	0	-10000	0	0
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.02	0.14	0.63	6	-10000	0	6
TNF	-0.009	0.19	-10000	0	-0.81	7	7
FASLG	-0.012	0.25	-10000	0	-1.1	9	9
TBX21	-0.058	0.14	-10000	0	-0.36	46	46
BATF3	-0.004	0.053	-10000	0	-0.56	2	2
PRKCQ	-0.017	0.14	-10000	0	-0.65	10	10
PTPN1	0.026	0.086	-10000	0	-10000	0	0
NFAT1-c-4/ICER1	-0.037	0.17	-10000	0	-0.76	9	9
GATA3	-0.077	0.24	-10000	0	-0.8	25	25
T-helper 1 cell differentiation	-0.052	0.11	-10000	0	-10000	0	0
IL2RA	-0.11	0.2	-10000	0	-0.96	6	6
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	0.026	0.086	-10000	0	-10000	0	0
E2F1	-0.1	0.15	-10000	0	-0.32	84	84
PPARG	-0.006	0.044	-10000	0	-0.32	5	5
SLC3A2	0.026	0.086	-10000	0	-10000	0	0
IRF4	-0.046	0.11	-10000	0	-0.32	37	37
PTGS2	-0.21	0.36	-10000	0	-0.95	31	31
CSF2	-0.11	0.25	-10000	0	-0.92	8	8
JunB/Fra1/NFAT1-c-4	-0.041	0.17	-10000	0	-0.74	9	9
IL4	-0.036	0.22	-10000	0	-0.74	14	14
IL5	-0.082	0.26	-10000	0	-0.91	8	8
IL2	0.017	0.14	-10000	0	-0.84	1	1
IL3	-0.029	0.041	-10000	0	-10000	0	0
RNF128	-0.17	0.34	-10000	0	-0.86	52	52
NFATC1	0.02	0.14	-10000	0	-0.63	6	6
CDK4	-0.046	0.11	-10000	0	-10000	0	0
PTPRK	0.026	0.086	-10000	0	-10000	0	0
IL8	-0.14	0.26	-10000	0	-1	9	9
POU2F1	-0.001	0.02	-10000	0	-0.32	1	1

×

IL2 signaling events mediated by STAT5

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	-0.001	0.02	-9999	-0.32	1	1
ELF1	-0.03	0.068	-9999	-0.38	5	5
CCNA2	-0.094	0.15	-9999	-0.32	76	76
PIK3CA	0	0	-9999	-10000	0	0
JAK3	-0.025	0.086	-9999	-0.32	20	20
PIK3R1	-0.004	0.053	-9999	-0.56	2	2
JAK1	0	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.02	0.075	-9999	-0.66	2	2
SHC1	0	0	-9999	-10000	0	0
SP1	-0.008	0.053	-9999	-0.38	5	5
IL2RA	-0.042	0.17	-9999	-1	5	5
IL2RB	-0.042	0.11	-9999	-0.32	34	34
SOS1	0	0	-9999	-10000	0	0
IL2RG	-0.04	0.12	-9999	-0.35	29	29
G1/S transition of mitotic cell cycle	-0.004	0.14	-9999	-0.92	5	5
PTPN11	0	0	-9999	-10000	0	0
CCND2	0.003	0.14	-9999	-1	5	5
LCK	-0.039	0.11	-9999	-0.34	30	30
GRB2	0	0	-9999	-10000	0	0
IL2	0.001	0.001	-9999	-10000	0	0
CDK6	-0.003	0.049	-9999	-0.8	1	1
CCND3	0.028	0.081	-9999	-0.7	1	1

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	0.028	0.33	-9999	-0.92	9	9
HDAC7	-0.001	0.02	-9999	-0.32	1	1
HIF1A/ARNT/Cbp/p300/Src-1	-0.066	0.2	-9999	-0.78	7	7
SMAD4	0	0	-9999	-10000	0	0
ID2	0.028	0.33	-9999	-0.92	9	9
AP1	-0.04	0.15	-9999	-0.61	16	16
ABCG2	0.026	0.33	-9999	-0.92	9	9
HIF1A	0.001	0.052	-9999	-10000	0	0
TFF3	-0.08	0.45	-9999	-1	22	22
GATA2	-0.009	0.077	-9999	-0.57	4	4
AKT1	0.022	0.071	-9999	-10000	0	0
response to hypoxia	0.012	0.078	-9999	-10000	0	0
MCL1	0.028	0.33	-9999	-0.92	9	9
NDRG1	0.026	0.33	-9999	-0.92	9	9
SERPINE1	0.014	0.35	-9999	-1	11	11
FECH	0.028	0.33	-9999	-0.92	9	9
FURIN	0.028	0.33	-9999	-0.92	9	9
NCOA2	-0.021	0.096	-9999	-0.39	14	14
EP300	0.052	0.11	-9999	-0.33	2	2
HMOX1	0.027	0.33	-9999	-0.92	9	9
BHLHE40	0.028	0.33	-9999	-0.92	9	9
BHLHE41	0.023	0.34	-9999	-0.94	11	11
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.012	0.035	-9999	-10000	0	0
ENG	-0.012	0.027	-9999	-10000	0	0
JUN	-0.003	0.028	-9999	-0.32	2	2
RORA	0.026	0.33	-9999	-0.96	9	9
ABCB1	-0.12	0.34	-9999	-1.2	23	23
TFRC	0.028	0.33	-9999	-0.92	9	9
CXCR4	0.024	0.33	-9999	-0.92	9	9
TF	0.017	0.34	-9999	-0.94	9	9
CITED2	0.028	0.33	-9999	-0.92	9	9
HIF1A/ARNT	-0.059	0.3	-9999	-1	9	9
LDHA	-0.014	0.033	-9999	-10000	0	0
ETS1	0.028	0.33	-9999	-0.92	9	9
PGK1	0.028	0.33	-9999	-0.92	9	9
NOS2	0.023	0.33	-9999	-0.92	9	9
ITGB2	0.025	0.33	-9999	-0.92	9	9
ALDOA	0.028	0.33	-9999	-0.92	9	9
Cbp/p300/CITED2	-0.028	0.29	-9999	-0.94	10	10
FOS	-0.05	0.19	-9999	-0.8	16	16
HK2	0.011	0.35	-9999	-1	10	10
SP1	0.006	0.037	-9999	-10000	0	0
GCK	-0.07	0.32	-9999	-1.2	11	11
HK1	0.028	0.33	-9999	-0.92	9	9
NPM1	0.028	0.33	-9999	-0.92	9	9
EGLN1	0.028	0.33	-9999	-0.92	9	9
CREB1	0.014	0.001	-9999	-10000	0	0
PGM1	0.028	0.33	-9999	-0.92	9	9
SMAD3	-0.001	0.02	-9999	-0.32	1	1
EDN1	0.021	0.27	-9999	-1.3	8	8
IGFBP1	0.023	0.33	-9999	-0.93	9	9
VEGFA	0.019	0.25	-9999	-0.73	5	5
HIF1A/JAB1	-0.007	0.017	-9999	-10000	0	0
CP	-0.084	0.46	-9999	-1	27	27
CXCL12	0.019	0.35	-9999	-1	9	9
COPS5	0	0	-9999	-10000	0	0
SMAD3/SMAD4	-0.001	0.013	-9999	-10000	0	0
BNIP3	0.021	0.34	-9999	-1	10	10
EGLN3	-0.027	0.4	-9999	-1	18	18
CA9	0	0.36	-9999	-0.97	12	12
TERT	0.023	0.33	-9999	-0.92	9	9
ENO1	0.028	0.33	-9999	-0.92	9	9
PFKL	0.028	0.33	-9999	-0.92	9	9
NCOA1	0	0	-9999	-10000	0	0
ADM	0.026	0.33	-9999	-0.93	10	10
ARNT	0.001	0.052	-9999	-10000	0	0
HNF4A	-0.37	0.4	-9999	-0.8	119	119
ADFP	0.023	0.33	-9999	-0.92	9	9
SLC2A1	0.012	0.26	-9999	-0.81	6	6
LEP	0.018	0.33	-9999	-0.93	9	9
HIF1A/ARNT/Cbp/p300	-0.066	0.22	-9999	-0.8	8	8
EPO	0.061	0.24	-9999	-10000	0	0
CREBBP	0.052	0.11	-9999	-0.33	2	2
HIF1A/ARNT/Cbp/p300/HDAC7	-0.069	0.21	-9999	-0.8	8	8
PFKFB3	0.028	0.33	-9999	-0.92	9	9
NT5E	0.022	0.34	-9999	-0.94	10	10

×

Signaling events mediated by PTP1B

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
PDGFRB	-0.001	0.02	-10000	0	-0.32	1	1
Jak2/Leptin Receptor	-0.049	0.087	-10000	0	-0.37	8	8
PTP1B/AKT1	-0.044	0.069	-10000	0	-0.29	11	11
FYN	-0.001	0.02	-10000	0	-0.32	1	1
p210 bcr-abl/PTP1B	-0.036	0.092	-10000	0	-0.34	11	11
EGFR	-0.006	0.058	-10000	0	-0.5	3	3
EGF/EGFR	-0.2	0.24	-10000	0	-0.48	103	103
CSF1	-0.006	0.044	-10000	0	-0.32	5	5
AKT1	0	0	-10000	0	-10000	0	0
INSR	0	0	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.14	0.19	-10000	0	-0.45	62	62
Insulin Receptor/Insulin	-0.029	0.05	-10000	0	-10000	0	0
HCK	-0.015	0.068	-10000	0	-0.32	12	12
CRK	0	0	-10000	0	-10000	0	0
TYK2	-0.027	0.088	-10000	0	-0.32	11	11
EGF	-0.32	0.39	-10000	0	-0.8	102	102
YES1	0	0	-10000	0	-10000	0	0
CAV1	-0.07	0.13	-10000	0	-0.38	13	13
TXN	0	0	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.043	0.069	-10000	0	-0.3	11	11
cell migration	0.036	0.092	0.34	11	-10000	0	11
STAT3	0	0	-10000	0	-10000	0	0
PRLR	-0.088	0.24	-10000	0	-0.65	35	35
ITGA2B	-0.007	0.048	-10000	0	-0.32	6	6
CSF1R	-0.009	0.085	-10000	0	-0.8	3	3
Prolactin Receptor/Prolactin	-0.1	0.2	-10000	0	-0.59	30	30
FGR	0	0	-10000	0	-10000	0	0
PTP1B/p130 Cas	-0.048	0.074	-10000	0	-0.32	11	11
Crk/p130 Cas	-0.043	0.069	-10000	0	-0.32	3	3
DOK1	-0.017	0.078	-10000	0	-0.3	3	3
JAK2	-0.042	0.1	-10000	0	-0.4	8	8
Jak2/Leptin Receptor/Leptin	-0.037	0.066	-10000	0	-0.36	1	1
PIK3R1	-0.004	0.053	-10000	0	-0.56	2	2
PTPN1	-0.036	0.093	-10000	0	-0.34	11	11
LYN	0	0	-10000	0	-10000	0	0
CDH2	-0.16	0.32	-10000	0	-0.8	51	51
SRC	-0.003	0.037	-10000	0	-10000	0	0
ITGB3	-0.015	0.11	-10000	0	-0.8	5	5
CAT1/PTP1B	-0.081	0.13	-10000	0	-0.36	14	14
CAPN1	0	0.001	-10000	0	-10000	0	0
CSK	0	0	-10000	0	-10000	0	0
PI3K	-0.024	0.052	-10000	0	-0.4	1	1
mol:H2O2	-0.003	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	-0.033	0.06	-10000	0	-10000	0	0
negative regulation of transcription	-0.042	0.099	-10000	0	-0.4	8	8
FCGR2A	-0.004	0.034	-10000	0	-0.32	3	3
FER	0	0	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.017	0.093	-10000	0	-0.64	5	5
BLK	-0.035	0.1	-10000	0	-0.32	28	28
Insulin Receptor/Insulin/Shc	0	0	-10000	0	-10000	0	0
RHOA	0	0.001	-10000	0	-10000	0	0
LEPR	-0.002	0.029	-10000	0	-0.32	2	2
BCAR1	0	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0	0	-10000	0	-10000	0	0
mol:NADPH	-0.003	0.004	-10000	0	-10000	0	0
TRPV6	-0.057	0.13	-10000	0	-0.32	11	11
PRL	-0.059	0.12	-10000	0	-0.32	47	47
SOCS3	0.015	0.013	-10000	0	-10000	0	0
SPRY2	-0.009	0.067	-10000	0	-0.4	6	6
Insulin Receptor/Insulin/IRS1	-0.001	0.011	-10000	0	-10000	0	0
CSF1/CSF1R	-0.05	0.098	-10000	0	-0.55	5	5
Ras protein signal transduction	0.025	0.028	-10000	0	-10000	0	0
IRS1	-0.001	0.02	-10000	0	-0.32	1	1
INS	0	0.001	-10000	0	-10000	0	0
LEP	-0.022	0.082	-10000	0	-10000	0	0
STAT5B	-0.037	0.084	-10000	0	-0.3	11	11
STAT5A	-0.037	0.084	-10000	0	-0.3	11	11
GRB2	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.048	0.074	-10000	0	-0.32	11	11
CSN2	-0.019	0.069	-10000	0	-10000	0	0
PIK3CA	0	0	-10000	0	-10000	0	0
LAT	-0.004	0.037	-10000	0	-10000	0	0
YBX1	0	0	-10000	0	-10000	0	0
LCK	-0.039	0.11	-10000	0	-0.34	30	30
SHC1	0	0	-10000	0	-10000	0	0
NOX4	-0.068	0.22	-10000	0	-0.8	22	22

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0.005	0.025	0.092	1	-10000	0	1
BUB1B	-0.031	0.051	-10000	0	-0.16	1	1
PLK1	0.002	0.018	-10000	0	-0.1	1	1
PLK1S1	0.005	0.01	-10000	0	-10000	0	0
KIF2A	0.01	0.016	-10000	0	-10000	0	0
regulation of mitotic centrosome separation	0.002	0.018	-10000	0	-0.1	1	1
GOLGA2	-0.001	0.02	-10000	0	-0.32	1	1
Hec1/SPC24	-0.12	0.12	-10000	0	-0.3	64	64
WEE1	0.006	0.019	-10000	0	-10000	0	0
cytokinesis	-0.034	0.058	-10000	0	-10000	0	0
PP2A-alpha B56	0.011	0.013	-10000	0	-10000	0	0
AURKA	0.005	0.012	-10000	0	-10000	0	0
PICH/PLK1	-0.043	0.078	-10000	0	-0.29	6	6
CENPE	-0.038	0.085	-10000	0	-0.2	9	9
RhoA/GTP	0	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.01	0.016	-10000	0	-10000	0	0
PPP2CA	0	0	-10000	0	-10000	0	0
FZR1	0	0	-10000	0	-10000	0	0
TPX2	-0.005	0.019	-10000	0	-10000	0	0
PAK1	0	0	-10000	0	-10000	0	0
SPC24	-0.15	0.16	-10000	0	-0.32	120	120
FBXW11	0	0	-10000	0	-10000	0	0
CLSPN	-0.005	0.019	-10000	0	-10000	0	0
GORASP1	0	0	-10000	0	-10000	0	0
metaphase	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.001	0.01	-10000	0	-0.061	1	1
G2 phase of mitotic cell cycle	0	0.001	-10000	0	-10000	0	0
STAG2	0	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0	0.004	-10000	0	-10000	0	0
spindle elongation	0.002	0.018	-10000	0	-0.1	1	1
ODF2	0	0	-10000	0	-10000	0	0
BUB1	0.008	0.01	-10000	0	-10000	0	0
TPT1	0.005	0.01	-10000	0	-10000	0	0
CDC25C	-0.012	0.016	-10000	0	-10000	0	0
CDC25B	-0.001	0.02	-10000	0	-0.32	1	1
SGOL1	-0.005	0.025	-10000	0	-0.092	1	1
RHOA	0	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.008	0.032	-10000	0	-10000	0	0
CDC14B	0.004	0.056	-10000	0	-0.63	2	2
CDC20	-0.11	0.15	-10000	0	-0.32	89	89
PLK1/PBIP1	-0.01	0.033	-10000	0	-10000	0	0
mitosis	-0.001	0.003	-10000	0	-0.024	1	1
FBXO5	0.007	0.02	-10000	0	-10000	0	0
CDC2	0	0.002	-10000	0	-10000	0	0
NDC80	-0.098	0.15	-10000	0	-0.32	79	79
metaphase plate congression	0.003	0.013	-10000	0	-10000	0	0
ERCC6L	-0.039	0.074	-10000	0	-10000	0	0
NLP/gamma Tubulin	0.004	0.011	-10000	0	-10000	0	0
microtubule cytoskeleton organization	0.005	0.01	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	0	0.001	-10000	0	-10000	0	0
PPP1R12A	0	0	-10000	0	-10000	0	0
interphase	0	0.001	-10000	0	-10000	0	0
PLK1/PRC1-2	-0.12	0.12	-10000	0	-0.3	63	63
GRASP65/GM130/RAB1/GTP/PLK1	-0.001	0.008	-10000	0	-10000	0	0
RAB1A	0	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.009	0.019	-10000	0	-0.2	1	1
mitotic prometaphase	-0.001	0.001	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.008	0.027	-10000	0	-0.3	2	2
microtubule-based process	-0.086	0.082	-10000	0	-0.21	6	6
Golgi organization	0.002	0.018	-10000	0	-0.1	1	1
Cohesin/SA2	-0.004	0.009	-10000	0	-10000	0	0
PPP1CB/MYPT1	0	0	-10000	0	-10000	0	0
KIF20A	-0.17	0.16	-10000	0	-0.32	135	135
APC/C/CDC20	-0.059	0.081	-10000	0	-0.17	84	84
PPP2R1A	0	0	-10000	0	-10000	0	0
chromosome segregation	-0.01	0.033	-10000	0	-10000	0	0
PRC1	-0.081	0.14	-10000	0	-0.32	65	65
ECT2	0.009	0.02	-10000	0	-10000	0	0
C13orf34	0.008	0.019	-10000	0	-0.19	1	1
NUDC	0.004	0.012	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.031	0.05	-10000	0	-0.16	1	1
spindle assembly	0.004	0.015	-10000	0	-10000	0	0
spindle stabilization	0.005	0.01	-10000	0	-10000	0	0
APC/C/HCDH1	-0.004	0.047	-10000	0	-0.54	2	2
MKLP2/PLK1	-0.086	0.082	-10000	0	-0.21	6	6
CCNB1	-0.025	0.085	-10000	0	-0.32	20	20
PPP1CB	0	0	-10000	0	-10000	0	0
BTRC	0	0	-10000	0	-10000	0	0
ROCK2	0.011	0.013	-10000	0	-10000	0	0
TUBG1	0.005	0.01	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.009	0.031	-10000	0	-10000	0	0
MLF1IP	-0.005	0.049	-10000	0	-0.22	11	11
INCENP	-0.002	0.028	-10000	0	-0.32	2	2

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.018	0.053	-10000	0	-10000	0	0
SMARCC2	0	0	-10000	0	-10000	0	0
SMARCC1	0	0	-10000	0	-10000	0	0
TBX21	-0.072	0.13	-10000	0	-0.46	9	9
SUMO2	0.001	0.006	-10000	0	-10000	0	0
STAT1 (dimer)	0.013	0.02	-10000	0	-0.31	1	1
FKBP4	0	0	-10000	0	-10000	0	0
FKBP5	-0.007	0.048	-10000	0	-0.32	6	6
GR alpha/HSP90/FKBP51/HSP90	0.051	0.086	0.32	7	-10000	0	7
PRL	-0.064	0.12	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/TIF2	0.15	0.2	0.54	32	-0.48	2	34
RELA	-0.024	0.084	-10000	0	-0.29	1	1
FGG	0.11	0.15	0.5	14	-10000	0	14
GR beta/TIF2	0.055	0.11	0.32	13	-0.59	2	15
IFNG	-0.14	0.18	-10000	0	-0.67	10	10
apoptosis	-0.056	0.15	0.51	5	-0.65	1	6
CREB1	-0.041	0.12	-10000	0	-0.35	31	31
histone acetylation	-0.012	0.095	-10000	0	-0.37	7	7
BGLAP	-0.026	0.09	-10000	0	-10000	0	0
GR/PKAc	0.054	0.076	0.32	4	-10000	0	4
NF kappa B1 p50/RelA	-0.047	0.15	-10000	0	-0.47	16	16
SMARCD1	0	0	-10000	0	-10000	0	0
MDM2	0.035	0.085	0.27	10	-10000	0	10
GATA3	-0.07	0.24	-10000	0	-0.8	25	25
AKT1	0	0	-10000	0	-10000	0	0
CSF2	-0.038	0.09	-10000	0	-0.49	1	1
GSK3B	0.001	0.006	-10000	0	-10000	0	0
NR1I3	-0.022	0.17	0.51	4	-1	2	6
CSN2	0.091	0.12	0.42	8	-10000	0	8
BRG1/BAF155/BAF170/BAF60A	0	0	-10000	0	-10000	0	0
NFATC1	-0.001	0.02	-10000	0	-0.32	1	1
POU2F1	0	0.027	-10000	0	-0.32	1	1
CDKN1A	0.029	0.018	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0	0.005	-10000	0	-10000	0	0
SFN	-0.057	0.19	-10000	0	-0.59	25	25
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.02	0.14	0.33	5	-0.46	12	17
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.026	0.18	0.49	4	-0.83	5	9
JUN	-0.075	0.13	-10000	0	-0.55	7	7
IL4	-0.042	0.096	-10000	0	-10000	0	0
CDK5R1	-0.008	0.052	-10000	0	-0.32	7	7
PRKACA	0	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.083	0.16	-10000	0	-0.56	14	14
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.051	0.083	0.32	5	-10000	0	5
cortisol/GR alpha (monomer)	0.18	0.23	0.63	33	-10000	0	33
NCOA2	-0.021	0.096	-10000	0	-0.39	14	14
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.064	0.2	-10000	0	-0.82	16	16
AP-1/NFAT1-c-4	-0.14	0.22	-10000	0	-0.71	19	19
AFP	-0.055	0.11	-10000	0	-0.65	1	1
SUV420H1	0	0	-10000	0	-10000	0	0
IRF1	0.091	0.11	0.44	8	-10000	0	8
TP53	0.026	0	-10000	0	-10000	0	0
PPP5C	0	0	-10000	0	-10000	0	0
KRT17	-0.23	0.43	-10000	0	-1.3	30	30
KRT14	-0.098	0.12	-10000	0	-0.54	1	1
TBP	0.015	0.006	-10000	0	-10000	0	0
CREBBP	0.026	0.034	-10000	0	-10000	0	0
HDAC1	0	0	-10000	0	-10000	0	0
HDAC2	0.001	0.004	-10000	0	-10000	0	0
AP-1	-0.14	0.23	-10000	0	-0.71	19	19
MAPK14	0.001	0.006	-10000	0	-10000	0	0
MAPK10	-0.23	0.36	-10000	0	-0.8	75	75
MAPK11	0	0.021	-10000	0	-0.32	1	1
KRT5	-0.13	0.18	-10000	0	-0.71	10	10
interleukin-1 receptor activity	-0.001	0.003	-10000	0	-10000	0	0
NCOA1	0	0	-10000	0	-10000	0	0
STAT1	0.013	0.02	-10000	0	-0.31	1	1
CGA	-0.19	0.45	-10000	0	-1.3	35	35
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.074	0.091	0.35	8	-10000	0	8
MAPK3	0.001	0.006	-10000	0	-10000	0	0
MAPK1	0.001	0.006	-10000	0	-10000	0	0
ICAM1	-0.088	0.18	-10000	0	-0.58	16	16
NFKB1	-0.024	0.084	-10000	0	-0.27	6	6
MAPK8	-0.074	0.13	-10000	0	-0.49	12	12
MAPK9	0.001	0.006	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.058	0.16	0.52	5	-0.69	1	6
BAX	0.029	0.018	-10000	0	-10000	0	0
POMC	-0.11	0.3	-10000	0	-1.4	10	10
EP300	0.026	0.034	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/p53	0.17	0.19	0.55	31	-10000	0	31
proteasomal ubiquitin-dependent protein catabolic process	0.021	0.067	0.23	4	-10000	0	4
SGK1	0.071	0.044	-10000	0	-10000	0	0
IL13	-0.14	0.22	-10000	0	-0.79	16	16
IL6	-0.19	0.43	-10000	0	-1.3	30	30
PRKACG	0	0	-10000	0	-10000	0	0
IL5	-0.13	0.18	-10000	0	-0.73	6	6
IL2	-0.12	0.17	-10000	0	-0.74	6	6
CDK5	0.001	0.004	-10000	0	-10000	0	0
PRKACB	0	0	-10000	0	-10000	0	0
HSP90AA1	0	0	-10000	0	-10000	0	0
IL8	-0.12	0.27	-10000	0	-0.67	33	33
CDK5R1/CDK5	-0.004	0.035	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	-0.047	0.097	-10000	0	-0.44	1	1
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.15	0.18	0.52	29	-10000	0	29
SMARCA4	0	0	-10000	0	-10000	0	0
chromatin remodeling	0.1	0.11	0.4	14	-10000	0	14
NF kappa B1 p50/RelA/Cbp	-0.017	0.12	-10000	0	-0.42	2	2
JUN (dimer)	-0.075	0.13	-10000	0	-0.54	7	7
YWHAH	0	0	-10000	0	-10000	0	0
VIPR1	-0.11	0.32	-10000	0	-1.1	22	22
NR3C1	0.097	0.13	0.45	18	-10000	0	18
NR4A1	-0.049	0.21	-10000	0	-0.69	23	23
TIF2/SUV420H1	-0.014	0.069	-10000	0	-0.61	2	2
MAPKKK cascade	-0.056	0.15	0.51	5	-0.65	1	6
cortisol/GR alpha (dimer)/Src-1	0.16	0.19	0.55	30	-10000	0	30
PBX1	-0.033	0.16	-10000	0	-0.8	11	11
POU1F1	-0.01	0.044	-10000	0	-0.32	4	4
SELE	-0.23	0.49	-10000	0	-1.3	44	44
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.1	0.11	0.4	14	-10000	0	14
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.15	0.18	0.52	29	-10000	0	29
mol:cortisol	0.088	0.13	0.35	35	-10000	0	35
MMP1	-0.1	0.23	-10000	0	-1.4	7	7

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0	0	-9999	-10000	0	0
PDGFRB	0	0.021	-9999	-0.33	1	1
SPHK1	-0.014	0.03	-9999	-10000	0	0
mol:S1P	-0.019	0.038	-9999	-10000	0	0
S1P1/S1P/Gi	-0.11	0.24	-9999	-0.57	32	32
GNAO1	-0.1	0.27	-9999	-0.79	34	34
PDGFB-D/PDGFRB/PLCgamma1	-0.12	0.2	-9999	-0.67	16	16
PLCG1	-0.097	0.23	-9999	-0.74	15	15
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0	0.021	-9999	-0.33	1	1
GNAI2	0	0	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
GNAI1	-0.012	0.099	-9999	-0.8	4	4
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.012	0.012	-9999	-10000	0	0
S1P1/S1P	-0.025	0.053	-9999	-10000	0	0
negative regulation of cAMP metabolic process	-0.1	0.24	-9999	-0.55	32	32
MAPK3	-0.14	0.29	-9999	-0.62	55	55
calcium-dependent phospholipase C activity	-0.003	0.004	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
KDR	0	0	-9999	-10000	0	0
PLCB2	-0.022	0.048	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
RhoA/GTP	-0.023	0.043	-9999	-10000	0	0
receptor internalization	-0.024	0.05	-9999	-10000	0	0
PTGS2	-0.23	0.47	-9999	-1.1	55	55
Rac1/GTP	-0.023	0.043	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
VEGFA	0	0	-9999	-10000	0	0
negative regulation of T cell proliferation	-0.1	0.24	-9999	-0.55	32	32
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.053	0.2	-9999	-0.8	17	17
MAPK1	-0.14	0.29	-9999	-0.62	55	55
S1P1/S1P/PDGFB-D/PDGFRB	-0.031	0.065	-9999	-10000	0	0
ABCC1	0	0	-9999	-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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.018	0.055	-9999	-0.37	2	2
NF kappa B1 p50/RelA/I kappa B alpha	-0.007	0.021	-9999	-10000	0	0
AP1	-0.046	0.11	-9999	-0.42	17	17
mol:PIP3	-0.02	0.063	-9999	-0.49	3	3
AKT1	-0.01	0.038	-9999	-0.36	1	1
PTK2B	0.013	0.039	-9999	-0.25	1	1
RHOA	-0.006	0.023	-9999	-10000	0	0
PIK3CB	0	0	-9999	-10000	0	0
mol:Ca2+	0.017	0.047	-9999	-10000	0	0
MAGI3	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
apoptosis	-0.017	0.047	-9999	-0.3	4	4
HRAS/GDP	0	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	-0.14	0.22	-9999	-0.41	99	99
NF kappa B1 p50/RelA	-0.015	0.04	-9999	-10000	0	0
endothelial cell migration	-0.036	0.12	-9999	-0.78	4	4
ADCY4	-0.032	0.14	-9999	-0.42	14	14
ADCY5	-0.14	0.25	-9999	-0.6	43	43
ADCY6	-0.032	0.14	-9999	-0.42	14	14
ADCY7	-0.032	0.14	-9999	-0.42	14	14
ADCY1	-0.036	0.14	-9999	-0.41	16	16
ADCY2	-0.065	0.18	-9999	-0.52	24	24
ADCY3	-0.032	0.14	-9999	-0.42	14	14
ADCY8	-0.059	0.15	-9999	-0.41	20	20
ADCY9	-0.032	0.14	-9999	-0.42	14	14
GSK3B	0.019	0.037	-9999	-10000	0	0
arachidonic acid secretion	-0.064	0.13	-9999	-0.35	35	35
GNG2	-0.007	0.048	-9999	-0.32	6	6
TRIP6	-0.004	0.014	-9999	-10000	0	0
GNAO1	-0.085	0.18	-9999	-0.52	37	37
HRAS	0	0	-9999	-10000	0	0
NFKBIA	0.027	0.044	-9999	-10000	0	0
GAB1	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	0	0.002	-9999	-10000	0	0
JUN	-0.002	0.028	-9999	-0.32	2	2
LPA/LPA2/NHERF2	-0.01	0.033	-9999	-10000	0	0
TIAM1	0.003	0.007	-9999	-10000	0	0
PIK3R1	-0.004	0.053	-9999	-0.56	2	2
mol:IP3	0.017	0.048	-9999	-10000	0	0
PLCB3	-0.008	0.028	-9999	-10000	0	0
FOS	-0.049	0.19	-9999	-0.8	16	16
positive regulation of mitosis	-0.064	0.13	-9999	-0.35	35	35
LPA/LPA1-2-3	-0.025	0.061	-9999	-0.32	5	5
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
stress fiber formation	0.016	0.047	-9999	-0.32	1	1
GNAZ	-0.052	0.15	-9999	-0.52	21	21
EGFR/PI3K-beta/Gab1	-0.021	0.066	-9999	-0.51	3	3
positive regulation of dendritic cell cytokine production	-0.025	0.061	-9999	-0.32	5	5
LPA/LPA2/MAGI-3	-0.01	0.033	-9999	-10000	0	0
ARHGEF1	-0.013	0.045	-9999	-0.44	1	1
GNAI2	-0.017	0.057	-9999	-0.36	4	4
GNAI3	-0.017	0.057	-9999	-0.36	4	4
GNAI1	-0.025	0.085	-9999	-0.44	8	8
LPA/LPA3	-0.015	0.046	-9999	-0.21	10	10
LPA/LPA2	-0.014	0.043	-9999	-0.21	9	9
LPA/LPA1	-0.022	0.07	-9999	-0.33	7	7
HB-EGF/EGFR	-0.071	0.092	-9999	-0.43	4	4
HBEGF	-0.076	0.12	-9999	-0.61	1	1
mol:DAG	0.017	0.048	-9999	-10000	0	0
cAMP biosynthetic process	-0.07	0.19	-9999	-0.48	38	38
NFKB1	0	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
GNB1	0	0	-9999	-10000	0	0
LYN	0.027	0.044	-9999	-10000	0	0
GNAQ	-0.011	0.029	-9999	-10000	0	0
LPAR2	-0.011	0.059	-9999	-0.32	9	9
LPAR3	-0.012	0.062	-9999	-0.32	10	10
LPAR1	-0.016	0.065	-9999	-0.43	4	4
IL8	-0.02	0.12	-9999	-0.49	9	9
PTK2	-0.022	0.055	-9999	-0.44	1	1
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.017	0.047	-9999	-0.3	4	4
EGFR	-0.006	0.057	-9999	-0.48	3	3
PLCG1	-0.017	0.043	-9999	-0.24	2	2
PLD2	-0.022	0.055	-9999	-0.44	1	1
G12/G13	-0.015	0.05	-9999	-0.32	4	4
PI3K-beta	-0.013	0.045	-9999	-0.39	2	2
cell migration	-0.004	0.015	-9999	-10000	0	0
SLC9A3R2	0	0	-9999	-10000	0	0
PXN	0.016	0.048	-9999	-0.33	1	1
HRAS/GTP	-0.066	0.13	-9999	-0.36	35	35
RAC1	0	0	-9999	-10000	0	0
MMP9	-0.13	0.16	-9999	-0.32	105	105
PRKCE	0	0	-9999	-10000	0	0
PRKCD	0.023	0.046	-9999	-10000	0	0
Gi(beta/gamma)	-0.061	0.12	-9999	-0.41	15	15
mol:LPA	-0.011	0.036	-9999	-0.22	3	3
TRIP6/p130 Cas/FAK1/Paxillin	-0.01	0.039	-9999	-0.4	1	1
MAPKKK cascade	-0.064	0.13	-9999	-0.35	35	35
contractile ring contraction involved in cytokinesis	0.017	0.03	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.037	0.11	-9999	-0.43	16	16
GNA15	-0.013	0.033	-9999	-10000	0	0
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
MAPT	-0.15	0.22	-9999	-0.42	99	99
GNA11	-0.012	0.039	-9999	-0.43	1	1
Rac1/GTP	0.001	0.007	-9999	-10000	0	0
MMP2	-0.037	0.12	-9999	-0.79	4	4

×

Insulin Pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.14	0.2	-9999	-0.42	84	84
TC10/GTP	-0.13	0.19	-9999	-0.41	84	84
Insulin Receptor/Insulin/IRS1/Shp2	-0.001	0.009	-9999	-10000	0	0
HRAS	0	0	-9999	-10000	0	0
APS homodimer	-0.001	0.02	-9999	-0.32	1	1
GRB14	-0.24	0.37	-9999	-0.8	78	78
FOXO3	-0.02	0.031	-9999	-10000	0	0
AKT1	-0.12	0.17	-9999	-0.37	78	78
INSR	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0	0	-9999	-10000	0	0
SORBS1	-0.26	0.37	-9999	-0.8	84	84
CRK	0	0	-9999	-10000	0	0
PTPN1	0.031	0	-9999	-10000	0	0
CAV1	-0.002	0.03	-9999	-0.47	1	1
CBL/APS/CAP/Crk-II/C3G	-0.15	0.21	-9999	-0.45	84	84
Insulin Receptor/Insulin/IRS1/NCK2	-0.001	0.009	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.003	0.029	-9999	-0.43	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0	0.003	-9999	-10000	0	0
RPS6KB1	-0.1	0.16	-9999	-10000	0	0
PARD6A	-0.003	0.049	-9999	-0.8	1	1
CBL	0	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0	-9999	-10000	0	0
PIK3R1	-0.004	0.053	-9999	-0.56	2	2
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.1	0.15	-9999	-10000	0	0
HRAS/GTP	-0.002	0.012	-9999	-10000	0	0
Insulin Receptor	0	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.001	0.008	-9999	-10000	0	0
PRKCI	-0.031	0.046	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.12	0.18	-9999	-0.4	79	79
SHC1	0	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0	0	-9999	-10000	0	0
PI3K	-0.003	0.029	-9999	-0.44	1	1
NCK2	0	0	-9999	-10000	0	0
RHOQ	0	0	-9999	-10000	0	0
mol:H2O2	0	0	-9999	-10000	0	0
HRAS/GDP	0	0	-9999	-10000	0	0
AKT2	-0.12	0.17	-9999	-10000	0	0
PRKCZ	-0.1	0.22	-9999	-0.69	29	29
SH2B2	-0.001	0.02	-9999	-0.32	1	1
SHC/SHIP	-0.002	0.017	-9999	-10000	0	0
F2RL2	-0.057	0.13	-9999	-0.33	44	44
TRIP10	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	0	0	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0	0	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	-0.16	0.22	-9999	-0.48	84	84
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0	0	-9999	-10000	0	0
INPP5D	-0.003	0.019	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
SGK1	-0.009	0.014	-9999	-10000	0	0
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
IRS1	-0.001	0.02	-9999	-0.32	1	1
p62DOK/RasGAP	0	0	-9999	-10000	0	0
INS	0.003	0	-9999	-10000	0	0
mol:PI-3-4-P2	-0.003	0.019	-9999	-10000	0	0
GRB2	0	0	-9999	-10000	0	0
EIF4EBP1	-0.1	0.16	-9999	-10000	0	0
PTPRA	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0	0.003	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1	-0.001	0.01	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS3	0	0	-9999	-10000	0	0
Par3/Par6	-0.025	0.061	-9999	-0.45	2	2

×

Visual signal transduction: Rods

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	-0.001	0.02	-9999	-0.32	1	1
GNAT1/GTP	0	0	-9999	-10000	0	0
Metarhodopsin II/Arrestin	-0.001	0.016	-9999	-10000	0	0
PDE6G/GNAT1/GTP	-0.008	0.067	-9999	-0.54	4	4
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0	0	-9999	-10000	0	0
GRK1	-0.007	0.048	-9999	-0.32	6	6
CNG Channel	-0.029	0.1	-9999	-0.49	10	10
mol:Na +	-0.021	0.067	-9999	-0.42	4	4
mol:ADP	-0.007	0.048	-9999	-0.32	6	6
RGS9-1/Gbeta5/R9AP	-0.14	0.25	-9999	-0.56	65	65
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.022	0.069	-9999	-0.43	4	4
CNGB1	-0.002	0.028	-9999	-0.32	2	2
RDH5	-0.052	0.2	-9999	-0.8	17	17
SAG	-0.002	0.028	-9999	-0.32	2	2
mol:Ca2+	-0.02	0.064	-9999	-10000	0	0
Na + (4 Units)	-0.02	0.062	-9999	-10000	0	0
RGS9	-0.12	0.28	-9999	-0.8	38	38
GNB1/GNGT1	-0.002	0.018	-9999	-10000	0	0
GNAT1/GDP	-0.12	0.22	-9999	-0.48	65	65
GUCY2D	-0.019	0.075	-9999	-0.32	15	15
GNGT1	-0.002	0.028	-9999	-0.32	2	2
GUCY2F	0	0	-9999	-10000	0	0
GNB5	0	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.024	0.094	-9999	-0.56	6	6
mol:11-cis-retinal	-0.052	0.2	-9999	-0.8	17	17
mol:cGMP	-0.016	0.051	-9999	-10000	0	0
GNB1	0	0	-9999	-10000	0	0
Rhodopsin	-0.041	0.15	-9999	-0.62	17	17
SLC24A1	-0.001	0.02	-9999	-0.32	1	1
CNGA1	-0.014	0.1	-9999	-0.7	5	5
Metarhodopsin II	-0.004	0.024	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.017	0.055	-9999	-10000	0	0
RGS9BP	-0.096	0.26	-9999	-0.8	31	31
Metarhodopsin II/Transducin	-0.001	0.006	-9999	-10000	0	0
GCAP Family/Ca ++	-0.008	0.035	-9999	-10000	0	0
PDE6A/B	-0.024	0.09	-9999	-0.67	3	3
mol:Pi	-0.14	0.25	-9999	-0.55	65	65
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.001	0.014	-9999	-10000	0	0
PDE6B	-0.009	0.085	-9999	-0.8	3	3
PDE6A	-0.026	0.088	-9999	-0.32	21	21
PDE6G	-0.012	0.098	-9999	-0.8	4	4
RHO	0	0	-9999	-10000	0	0
PDE6	-0.13	0.21	-9999	-0.46	71	71
GUCA1A	-0.015	0.068	-9999	-0.32	12	12
GC2/GCAP Family	-0.008	0.035	-9999	-10000	0	0
GUCA1C	-0.001	0.02	-9999	-0.32	1	1
GUCA1B	-0.001	0.02	-9999	-0.32	1	1

×

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

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
MAP4K1	0.01	0.11	-10000	0	-0.39	14	14
CRKL	0.014	0.1	-10000	0	-0.41	14	14
HRAS	-0.024	0.079	-10000	0	-0.4	1	1
mol:PIP3	0	0.098	-10000	0	-0.39	15	15
SPRED1	0	0	-10000	0	-10000	0	0
SPRED2	-0.002	0.028	-10000	0	-0.32	2	2
GAB1	-0.025	0.1	-10000	0	-0.43	15	15
FOXO3	0.017	0.096	-10000	0	-0.37	14	14
AKT1	0.011	0.1	-10000	0	-0.41	14	14
BAD	0.017	0.096	-10000	0	-0.37	14	14
megakaryocyte differentiation	0.001	0.12	-10000	0	-0.42	19	19
GSK3B	0.017	0.096	-10000	0	-0.37	14	14
RAF1	0.032	0.081	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
STAT3	-0.025	0.1	-10000	0	-0.43	15	15
STAT1	-0.005	0.25	-10000	0	-1.1	14	14
HRAS/SPRED1	-0.019	0.064	-10000	0	-10000	0	0
cell proliferation	0.006	0.11	-10000	0	-0.42	16	16
PIK3CA	0	0	-10000	0	-10000	0	0
TEC	-0.009	0.085	-10000	0	-0.8	3	3
RPS6KB1	0.006	0.11	-10000	0	-0.43	15	15
HRAS/SPRED2	-0.019	0.065	-10000	0	-10000	0	0
LYN/TEC/p62DOK	-0.028	0.11	-10000	0	-0.42	17	17
MAPK3	0.037	0.062	-10000	0	-10000	0	0
STAP1	-0.083	0.19	-10000	0	-0.48	45	45
GRAP2	-0.011	0.059	-10000	0	-0.32	9	9
JAK2	-0.049	0.2	-10000	0	-0.88	14	14
STAT1 (dimer)	-0.004	0.25	-10000	0	-1	14	14
mol:Gleevec	-0.002	0.004	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.032	0.1	-10000	0	-0.41	15	15
actin filament polymerization	0.007	0.11	-10000	0	-0.42	15	15
LYN	0	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.087	0.21	-10000	0	-0.75	14	14
PIK3R1	-0.004	0.053	-10000	0	-0.56	2	2
CBL/CRKL/GRB2	-0.021	0.084	-10000	0	-10000	0	0
PI3K	-0.025	0.097	-10000	0	-0.41	15	15
PTEN	0	0	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.073	0.3	-10000	0	-1.3	14	14
MAPK8	-0.027	0.1	-10000	0	-0.43	16	16
STAT3 (dimer)	0.008	0.11	-10000	0	-0.42	15	15
positive regulation of transcription	0.035	0.053	-10000	0	-10000	0	0
mol:GDP	-0.028	0.085	-10000	0	-0.44	1	1
PIK3C2B	-0.025	0.1	-10000	0	-0.43	15	15
CBL/CRKL	-0.022	0.089	-10000	0	-0.38	14	14
FER	-0.025	0.1	-10000	0	-0.43	15	15
SH2B3	-0.025	0.1	-10000	0	-0.43	15	15
PDPK1	0.007	0.092	-10000	0	-0.36	14	14
SNAI2	-0.035	0.11	-10000	0	-0.45	14	14
positive regulation of cell proliferation	0.006	0.18	-10000	0	-0.76	14	14
KITLG	0.008	0.055	-10000	0	-0.56	2	2
cell motility	0.006	0.18	-10000	0	-0.76	14	14
PTPN6	0.001	0.022	-10000	0	-0.33	1	1
EPOR	0.028	0.072	-10000	0	-10000	0	0
STAT5A (dimer)	0.009	0.15	-10000	0	-0.62	14	14
SOCS1	-0.004	0.034	-10000	0	-0.32	3	3
cell migration	-0.001	0.11	0.43	15	-10000	0	15
SOS1	0	0	-10000	0	-10000	0	0
EPO	-0.003	0.034	-10000	0	-0.31	3	3
VAV1	-0.025	0.095	-10000	0	-0.35	19	19
GRB10	-0.025	0.1	-10000	0	-0.43	15	15
PTPN11	0.001	0.006	-10000	0	-10000	0	0
SCF/KIT	-0.027	0.11	-10000	0	-0.46	15	15
GO:0007205	-0.001	0.006	-10000	0	-10000	0	0
MAP2K1	0.036	0.067	-10000	0	-10000	0	0
CBL	0	0	-10000	0	-10000	0	0
KIT	-0.036	0.34	-10000	0	-1.4	14	14
MAP2K2	0.036	0.067	-10000	0	-10000	0	0
SHC/Grb2/SOS1	-0.023	0.093	-10000	0	-0.4	14	14
STAT5A	0.008	0.16	-10000	0	-0.64	14	14
GRB2	0	0	-10000	0	-10000	0	0
response to radiation	-0.005	0.11	-10000	0	-0.44	14	14
SHC/GRAP2	-0.007	0.038	-10000	0	-10000	0	0
PTPRO	-0.032	0.11	-10000	0	-0.43	19	19
SH2B2	-0.026	0.1	-10000	0	-0.43	15	15
DOK1	0	0	-10000	0	-10000	0	0
MATK	-0.031	0.11	-10000	0	-0.44	15	15
CREBBP	0.028	0.007	-10000	0	-10000	0	0
BCL2	0.028	0.07	-10000	0	-10000	0	0

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.016	0.015	-9999	-10000	0	0
SMARCC1	0.007	0.009	-9999	-10000	0	0
REL	0.003	0.009	-9999	-10000	0	0
HDAC7	-0.14	0.14	-9999	-0.65	7	7
JUN	-0.002	0.028	-9999	-0.32	2	2
EP300	0	0	-9999	-10000	0	0
KAT2B	0	0	-9999	-10000	0	0
KAT5	0	0	-9999	-10000	0	0
MAPK14	-0.024	0.1	-9999	-0.64	7	7
FOXO1	0	0	-9999	-10000	0	0
T-DHT/AR	-0.16	0.15	-9999	-0.61	10	10
MAP2K6	-0.026	0.13	-9999	-0.82	7	7
BRM/BAF57	-0.001	0.003	-9999	-10000	0	0
MAP2K4	-0.004	0.006	-9999	-10000	0	0
SMARCA2	0	0.001	-9999	-10000	0	0
PDE9A	-0.39	0.54	-9999	-1.3	64	64
NCOA2	-0.021	0.097	-9999	-0.39	14	14
CEBPA	-0.004	0.034	-9999	-0.32	3	3
EHMT2	0	0	-9999	-10000	0	0
cell proliferation	-0.15	0.15	-9999	-0.51	12	12
NR0B1	-0.017	0.073	-9999	-0.32	14	14
EGR1	-0.012	0.098	-9999	-0.8	4	4
RXRs/9cRA	-0.035	0.1	-9999	-0.49	10	10
AR/RACK1/Src	-0.094	0.11	-9999	-0.56	8	8
AR/GR	-0.038	0.079	-9999	-0.36	9	9
GNB2L1	-0.001	0.02	-9999	-0.32	1	1
PKN1	0	0	-9999	-10000	0	0
RCHY1	0	0	-9999	-10000	0	0
epidermal growth factor receptor activity	-0.003	0.004	-9999	-10000	0	0
MAPK8	-0.009	0.043	-9999	-0.64	1	1
T-DHT/AR/TIF2/CARM1	-0.09	0.12	-9999	-0.59	9	9
SRC	-0.039	0.097	-9999	-0.52	8	8
NR3C1	0	0	-9999	-10000	0	0
KLK3	-0.14	0.41	-9999	-1.3	29	29
APPBP2	-0.001	0.003	-9999	-10000	0	0
TRIM24	0	0	-9999	-10000	0	0
T-DHT/AR/TIP60	-0.069	0.1	-9999	-0.56	8	8
TMPRSS2	-0.73	0.62	-9999	-1.3	145	145
RXRG	-0.065	0.18	-9999	-0.45	37	37
mol:9cRA	-0.001	0.002	-9999	-10000	0	0
RXRA	0	0	-9999	-10000	0	0
RXRB	0	0	-9999	-10000	0	0
CARM1	0	0	-9999	-10000	0	0
NR2C2	0	0	-9999	-10000	0	0
KLK2	-0.25	0.37	-9999	-0.81	75	75
AR	-0.049	0.089	-9999	-0.35	18	18
SENP1	-0.001	0.02	-9999	-0.32	1	1
HSP90AA1	0	0	-9999	-10000	0	0
MDM2	-0.058	0.13	-9999	-0.32	50	50
SRY	0.004	0.011	-9999	-10000	0	0
GATA2	-0.009	0.075	-9999	-0.56	4	4
MYST2	0	0	-9999	-10000	0	0
HOXB13	-0.12	0.26	-9999	-0.6	51	51
T-DHT/AR/RACK1/Src	-0.077	0.1	-9999	-0.56	8	8
positive regulation of transcription	-0.009	0.075	-9999	-0.56	4	4
DNAJA1	-0.001	0.003	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.004	0.019	-9999	-10000	0	0
NCOA1	0.012	0.008	-9999	-10000	0	0
SPDEF	-0.004	0.035	-9999	-0.33	3	3
T-DHT/AR/TIF2	-0.022	0.07	-9999	-0.45	2	2
T-DHT/AR/Hsp90	-0.07	0.1	-9999	-0.56	8	8
GSK3B	0	0	-9999	-10000	0	0
NR2C1	0	0	-9999	-10000	0	0
mol:T-DHT	-0.046	0.1	-9999	-0.55	8	8
SIRT1	0	0	-9999	-10000	0	0
ZMIZ2	0.004	0.013	-9999	-10000	0	0
POU2F1	-0.013	0.057	-9999	-0.46	1	1
T-DHT/AR/DAX-1	-0.081	0.11	-9999	-0.58	8	8
CREBBP	0	0	-9999	-10000	0	0
SMARCE1	0	0.001	-9999	-10000	0	0

×

IL12-mediated signaling 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	0.022	0.075	-9999	-10000	0	0
TBX21	-0.007	0.23	-9999	-0.7	5	5
B2M	0	0	-9999	-10000	0	0
TYK2	0.013	0.013	-9999	-10000	0	0
IL12RB1	-0.015	0.1	-9999	-0.35	21	21
GADD45B	0.015	0.18	-9999	-0.68	2	2
IL12RB2	-0.003	0.073	-9999	-0.33	12	12
GADD45G	-0.002	0.23	-9999	-1	5	5
natural killer cell activation	0.003	0.017	-9999	-10000	0	0
RELB	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
IL18	-0.03	0.18	-9999	-0.8	13	13
IL2RA	-0.076	0.16	-9999	-0.36	54	54
IFNG	-0.08	0.14	-9999	-0.32	64	64
STAT3 (dimer)	-0.003	0.2	-9999	-0.54	11	11
HLA-DRB5	-0.023	0.12	-9999	-0.54	11	11
FASLG	-0.006	0.23	-9999	-0.7	5	5
NF kappa B2 p52/RelB	-0.077	0.15	-9999	-0.58	8	8
CD4	-0.007	0.048	-9999	-0.32	6	6
SOCS1	-0.004	0.034	-9999	-0.32	3	3
EntrezGene:6955	-0.001	0.008	-9999	-10000	0	0
CD3D	-0.052	0.14	-9999	-0.37	37	37
CD3E	-0.053	0.15	-9999	-0.41	33	33
CD3G	-0.086	0.14	-9999	-0.33	68	68
IL12Rbeta2/JAK2	0.008	0.057	-9999	-10000	0	0
CCL3	-0.013	0.23	-9999	-1	1	1
CCL4	-0.005	0.23	-9999	-1	1	1
HLA-A	0	0	-9999	-10000	0	0
IL18/IL18R	-0.006	0.16	-9999	-0.55	19	19
NOS2	0	0.23	-9999	-1.2	3	3
IL12/IL12R/TYK2/JAK2/SPHK2	0.023	0.075	-9999	-10000	0	0
IL1R1	-0.001	0.24	-9999	-1.2	3	3
IL4	-0.003	0.017	-9999	-10000	0	0
JAK2	0.012	0.024	-9999	-0.32	1	1
EntrezGene:6957	-0.001	0.007	-9999	-10000	0	0
TCR/CD3/MHC I/CD8	-0.033	0.13	-9999	-0.57	3	3
RAB7A	0.021	0.18	-9999	-0.62	1	1
lysosomal transport	0.023	0.18	-9999	-0.55	3	3
FOS	-0.071	0.35	-9999	-1.3	17	17
STAT4 (dimer)	0.017	0.2	-9999	-0.66	2	2
STAT5A (dimer)	-0.099	0.2	-9999	-0.6	26	26
GZMA	-0.009	0.23	-9999	-0.69	5	5
GZMB	-0.002	0.22	-9999	-1	1	1
HLX	-0.006	0.044	-9999	-0.32	5	5
LCK	-0.013	0.25	-9999	-0.65	23	23
TCR/CD3/MHC II/CD4	-0.034	0.14	-9999	-0.63	7	7
IL2/IL2R	-0.077	0.15	-9999	-0.52	17	17
MAPK14	0.012	0.2	-9999	-0.63	5	5
CCR5	-0.003	0.22	-9999	-0.95	3	3
IL1B	-0.024	0.16	-9999	-0.59	16	16
STAT6	0.016	0.082	-9999	-0.23	1	1
STAT4	-0.01	0.056	-9999	-0.32	8	8
STAT3	0	0	-9999	-10000	0	0
STAT1	-0.001	0.02	-9999	-0.32	1	1
NFKB1	0	0	-9999	-10000	0	0
NFKB2	0	0	-9999	-10000	0	0
IL12B	-0.006	0.08	-9999	-0.35	13	13
CD8A	-0.066	0.13	-9999	-0.33	52	52
CD8B	-0.045	0.12	-9999	-0.34	34	34
T-helper 1 cell differentiation	0	0	-9999	-10000	0	0
natural killer cell mediated cytotoxicity	-0.022	0.075	-9999	-10000	0	0
IL2RB	-0.042	0.11	-9999	-0.32	34	34
proteasomal ubiquitin-dependent protein catabolic process	0.02	0.19	-9999	-0.62	2	2
IL2RG	-0.04	0.12	-9999	-0.35	29	29
IL12	0.005	0.065	-9999	-10000	0	0
STAT5A	0	0	-9999	-10000	0	0
CD247	-0.028	0.092	-9999	-0.33	22	22
IL2	0	0	-9999	-10000	0	0
SPHK2	0	0	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
IL12A	0.01	0.031	-9999	-0.31	2	2
IL12/IL12R/TYK2/JAK2	-0.002	0.23	-9999	-0.64	11	11
MAP2K3	0.012	0.2	-9999	-0.61	5	5
RIPK2	0	0	-9999	-10000	0	0
MAP2K6	0.005	0.2	-9999	-0.59	6	6
regulation of dendritic cell antigen processing and presentation	0	0	-9999	-10000	0	0
HLA-DRA	-0.012	0.098	-9999	-0.8	4	4
IL18RAP	0	0.059	-9999	-0.33	8	8
IL12Rbeta1/TYK2	-0.003	0.075	-9999	-10000	0	0
EOMES	-0.025	0.06	-9999	-10000	0	0
STAT1 (dimer)	-0.004	0.2	-9999	-0.55	8	8
T cell proliferation	0.014	0.18	-9999	-0.56	2	2
T-helper 1 cell lineage commitment	0	0	-9999	-10000	0	0
IL18R1	-0.012	0.13	-9999	-0.8	7	7
CD8-positive alpha-beta T cell lineage commitment	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.079	0.15	-9999	-0.65	4	4
ATF2	0.019	0.19	-9999	-0.59	5	5

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.001	0.008	-10000	0	-10000	0	0
HDAC1	0	0.003	-10000	0	-10000	0	0
AES	0	0.001	-10000	0	-10000	0	0
FBXW11	0	0	-10000	0	-10000	0	0
DTX1	-0.064	0.21	-10000	0	-0.75	22	22
LRP6/FZD1	-0.006	0.036	-10000	0	-10000	0	0
TLE1	-0.005	0.04	-10000	0	-0.32	4	4
AP1	-0.06	0.14	-10000	0	-0.38	40	40
NCSTN	-0.001	0.02	-10000	0	-0.32	1	1
ADAM10	0	0	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.008	0.072	-10000	0	-0.68	1	1
NICD/RBPSUH	0	0.001	-10000	0	-10000	0	0
WIF1	-0.053	0.12	-10000	0	-0.32	43	43
NOTCH1	0	0.001	-10000	0	-10000	0	0
PSENEN	0	0	-10000	0	-10000	0	0
KREMEN2	-0.041	0.11	-10000	0	-0.32	33	33
DKK1	-0.13	0.24	-10000	0	-0.46	74	74
beta catenin/beta TrCP1	-0.001	0.005	-10000	0	-10000	0	0
APH1B	0	0	-10000	0	-10000	0	0
APH1A	0	0	-10000	0	-10000	0	0
AXIN1	-0.003	0.024	-10000	0	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	-0.017	0.075	-10000	0	-0.34	12	12
PSEN1	0	0	-10000	0	-10000	0	0
FOS	-0.049	0.19	-10000	0	-0.8	16	16
JUN	-0.002	0.028	-10000	0	-0.32	2	2
MAP3K7	0	0.002	-10000	0	-10000	0	0
CTNNB1	0.037	0.064	-10000	0	-10000	0	0
MAPK3	0	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.045	0.096	-10000	0	-0.39	10	10
HNF1A	-0.04	0.17	-10000	0	-0.8	13	13
CTBP1	0	0.001	-10000	0	-10000	0	0
MYC	-0.004	0.096	-10000	0	-1.5	1	1
NKD1	-0.083	0.24	-10000	0	-0.72	30	30
FZD1	-0.009	0.052	-10000	0	-0.32	7	7
NOTCH1 precursor/Deltex homolog 1	-0.035	0.12	-10000	0	-0.44	20	20
apoptosis	-0.06	0.14	-10000	0	-0.38	40	40
Delta 1/NOTCHprecursor	-0.001	0.008	-10000	0	-10000	0	0
DLL1	-0.001	0.02	-10000	0	-0.32	1	1
PPARD	0.002	0.01	-10000	0	-10000	0	0
Gamma Secretase	0	0.008	-10000	0	-10000	0	0
APC	-0.003	0.024	-10000	0	-10000	0	0
DVL1	-0.004	0.009	-10000	0	-10000	0	0
CSNK2A1	0	0	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.001	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.098	0.16	-10000	0	-0.53	24	24
LRP6	-0.001	0.02	-10000	0	-0.32	1	1
CSNK1A1	0	0	-10000	0	-10000	0	0
NLK	0	0.004	-10000	0	-10000	0	0
CCND1	-0.004	0.097	-10000	0	-1.5	1	1
WNT1	-0.029	0.091	-10000	0	-0.32	23	23
Axin1/APC/beta catenin	0.042	0.033	-10000	0	-10000	0	0
DKK2	-0.043	0.12	-10000	0	-0.35	32	32
NOTCH1 precursor/DVL1	0.002	0.006	-10000	0	-10000	0	0
GSK3B	0	0.001	-10000	0	-10000	0	0
FRAT1	0	0.001	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.035	0.12	-10000	0	-0.44	20	20
PPP2R5D	0.035	0.11	0.36	25	-10000	0	25
MAPK1	0	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.041	0.08	-10000	0	-0.45	1	1
RBPJ	0	0	-10000	0	-10000	0	0
CREBBP	0.011	0.001	-10000	0	-10000	0	0

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	-0.012	0.074	-10000	0	-0.53	5	5
fibroblast growth factor receptor signaling pathway	-0.012	0.074	-10000	0	-0.52	5	5
LAMA1	-0.035	0.14	-10000	0	-0.47	19	19
PRNP	0	0	-10000	0	-10000	0	0
GPC1/SLIT2	-0.04	0.14	-10000	0	-0.61	15	15
SMAD2	-0.002	0.015	-10000	0	-10000	0	0
GPC1/PrPc/Cu2+	-0.002	0.018	-10000	0	-10000	0	0
GPC1/Laminin alpha1	-0.027	0.1	-10000	0	-0.61	6	6
TDGF1	-0.027	0.14	-10000	0	-0.7	10	10
CRIPTO/GPC1	-0.023	0.11	-10000	0	-0.61	8	8
APP/GPC1	-0.005	0.044	-10000	0	-0.61	1	1
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.019	0.093	-10000	0	-0.52	8	8
FLT1	0	0	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	-0.002	0.018	-10000	0	-10000	0	0
SERPINC1	-0.026	0.14	-10000	0	-0.74	9	9
FYN	-0.02	0.094	-10000	0	-0.52	8	8
FGR	-0.019	0.093	-10000	0	-0.52	8	8
positive regulation of MAPKKK cascade	0.005	0.1	-10000	0	-0.52	8	8
SLIT2	-0.05	0.19	-10000	0	-0.72	18	18
GPC1/NRG	-0.08	0.2	-10000	0	-0.61	31	31
NRG1	-0.1	0.26	-10000	0	-0.72	37	37
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.002	0.018	-10000	0	-10000	0	0
LYN	-0.019	0.093	-10000	0	-0.52	8	8
mol:Spermine	0.007	0.024	-10000	0	-0.22	3	3
cell growth	-0.012	0.074	-10000	0	-0.52	5	5
BMP signaling pathway	0.004	0.034	0.32	3	-10000	0	3
SRC	-0.019	0.093	-10000	0	-0.52	8	8
TGFBR1	0	0	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.24	0.34	-10000	0	-0.8	64	64
GPC1	-0.004	0.034	-10000	0	-0.32	3	3
TGFBR1 (dimer)	0	0	-10000	0	-10000	0	0
VEGFA	0	0	-10000	0	-10000	0	0
BLK	-0.038	0.1	-10000	0	-0.52	8	8
HCK	-0.027	0.098	-10000	0	-0.52	8	8
FGF2	-0.015	0.11	-10000	0	-0.8	5	5
FGFR1	0	0	-10000	0	-10000	0	0
VEGFR1 homodimer	0	0	-10000	0	-10000	0	0
TGFBR2	0	0	-10000	0	-10000	0	0
cell death	-0.005	0.044	-10000	0	-0.61	1	1
ATIII/GPC1	-0.022	0.11	-10000	0	-0.61	8	8
PLA2G2A/GPC1	-0.18	0.26	-10000	0	-0.61	64	64
LCK	-0.04	0.11	-10000	0	-0.52	9	9
neuron differentiation	-0.08	0.2	-10000	0	-0.61	31	31
PrPc/Cu2+	0	0	-10000	0	-10000	0	0
APP	-0.003	0.049	-10000	0	-0.8	1	1
TGFBR2 (dimer)	0	0	-10000	0	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.023	0.036	-9999	-0.52	1	1
SNTA1	-0.003	0.049	-9999	-0.8	1	1
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.02	0.044	-9999	-0.52	1	1
MAPK12	-0.013	0.077	-9999	-0.48	7	7
CCND1	0.011	0.044	-9999	-0.46	1	1
p38 gamma/SNTA1	-0.014	0.077	-9999	-0.44	8	8
MAP2K3	0	0	-9999	-10000	0	0
PKN1	0	0	-9999	-10000	0	0
G2/M transition checkpoint	0.013	0.081	-9999	-0.47	7	7
MAP2K6	-0.014	0.085	-9999	-0.52	7	7
MAPT	-0.14	0.21	-9999	-0.4	100	100
MAPK13	0.015	0.042	-9999	-0.61	1	1
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0	0.006	-9999	-10000	0	0

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.001	0.02	-9999	-0.32	1	1
mol:S1P	0.001	0.002	-9999	-10000	0	0
S1P1/S1P/Gi	-0.064	0.15	-9999	-0.35	47	47
GNAO1	-0.1	0.27	-9999	-0.78	34	34
S1P/S1P3/G12/G13	-0.002	0.031	-9999	-0.48	1	1
AKT1	-0.022	0.049	-9999	-10000	0	0
AKT3	-0.001	0.12	-9999	-1.3	1	1
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.001	0.02	-9999	-0.32	1	1
GNAI2	0	0.001	-9999	-10000	0	0
GNAI3	0	0.001	-9999	-10000	0	0
GNAI1	-0.012	0.098	-9999	-0.8	4	4
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	-0.004	0.053	-9999	-0.56	2	2
S1PR2	-0.001	0.02	-9999	-0.32	1	1
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	-0.066	0.15	-9999	-0.4	34	34
MAPK3	-0.028	0.16	-9999	-0.62	8	8
MAPK1	-0.028	0.16	-9999	-0.62	8	8
JAK2	-0.029	0.16	-9999	-0.37	35	35
CXCR4	-0.036	0.16	-9999	-0.58	10	10
FLT1	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	-0.028	0.16	-9999	-0.62	8	8
S1P/S1P3/Gi	-0.067	0.15	-9999	-0.4	34	34
RAC1	0	0	-9999	-10000	0	0
RhoA/GTP	-0.06	0.14	-9999	-0.6	8	8
VEGFA	0	0	-9999	-10000	0	0
S1P/S1P2/Gi	-0.065	0.14	-9999	-0.39	34	34
VEGFR1 homodimer/VEGFA homodimer	0	0.003	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.026	0.1	-9999	-0.38	17	17
GNAQ	0	0	-9999	-10000	0	0
GNAZ	-0.052	0.2	-9999	-0.8	17	17
G12/G13	0	0	-9999	-10000	0	0
GNA14	-0.049	0.19	-9999	-0.8	16	16
GNA15	-0.006	0.044	-9999	-0.32	5	5
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
GNA11	-0.003	0.049	-9999	-0.8	1	1
Rac1/GTP	-0.06	0.14	-9999	-0.36	34	34

×

Regulation of nuclear SMAD2/3 signaling

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
EP300	0.01	0.009	-10000	0	-10000	0	0
HSPA8	0	0.001	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.005	0.11	0.25	1	-0.55	6	7
AKT1	0	0.004	-10000	0	-10000	0	0
GSC	-0.073	0.082	-10000	0	-10000	0	0
NKX2-5	-0.11	0.15	-10000	0	-0.32	88	88
muscle cell differentiation	0.005	0.045	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1	-0.006	0.027	-10000	0	-10000	0	0
SMAD4	0.006	0.021	-10000	0	-10000	0	0
CBFB	0	0	-10000	0	-10000	0	0
SAP18	0	0.001	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.017	0.055	-10000	0	-10000	0	0
SMAD3/SMAD4/VDR	-0.018	0.12	-10000	0	-0.43	18	18
MYC	0	0.051	-10000	0	-0.8	1	1
CDKN2B	0	0.11	-10000	0	-1.5	1	1
AP1	-0.021	0.1	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0	0.001	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.002	0.029	-10000	0	-10000	0	0
SP3	0	0	-10000	0	-10000	0	0
CREB1	0	0	-10000	0	-10000	0	0
FOXH1	-0.007	0.041	-10000	0	-0.33	3	3
SMAD3/SMAD4/GR	0.006	0.026	-10000	0	-10000	0	0
GATA3	-0.079	0.23	-10000	0	-0.79	25	25
SKI/SIN3/HDAC complex/NCoR1	0	0.004	-10000	0	-10000	0	0
MEF2C/TIF2	-0.048	0.071	-10000	0	-0.45	1	1
endothelial cell migration	0.008	0.11	1.5	1	-10000	0	1
MAX	0.003	0.008	-10000	0	-10000	0	0
RBBP7	0	0.001	-10000	0	-10000	0	0
RBBP4	0	0.001	-10000	0	-10000	0	0
RUNX2	-0.12	0.16	-10000	0	-0.32	97	97
RUNX3	-0.063	0.13	-10000	0	-0.32	51	51
RUNX1	-0.048	0.12	-10000	0	-0.32	39	39
CTBP1	0	0	-10000	0	-10000	0	0
NR3C1	0.003	0.008	-10000	0	-10000	0	0
VDR	-0.058	0.2	-10000	0	-0.75	20	20
CDKN1A	0.049	0.038	-10000	0	-10000	0	0
KAT2B	0	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	-0.006	0.027	-10000	0	-10000	0	0
DCP1A	0	0	-10000	0	-10000	0	0
SKI	0	0.001	-10000	0	-10000	0	0
SERPINE1	-0.008	0.11	-10000	0	-1.5	1	1
SMAD3/SMAD4/ATF2	0.006	0.026	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	-0.009	0.098	-10000	0	-0.58	7	7
SAP30	0	0.001	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.022	0.022	-10000	0	-10000	0	0
JUN	-0.004	0.11	-10000	0	-10000	0	0
SMAD3/SMAD4/IRF7	0.005	0.03	-10000	0	-10000	0	0
TFE3	0	0.002	-10000	0	-10000	0	0
COL1A2	-0.04	0.14	-10000	0	-1.2	2	2
mesenchymal cell differentiation	0.066	0.089	-10000	0	-10000	0	0
DLX1	-0.11	0.15	-10000	0	-0.32	90	90
TCF3	-0.002	0.028	-10000	0	-0.32	2	2
FOS	-0.049	0.19	-10000	0	-0.79	16	16
SMAD3/SMAD4/Max	0.006	0.026	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0	0	-10000	0	-10000	0	0
ZBTB17	0.003	0.008	-10000	0	-10000	0	0
LAMC1	0.033	0.028	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.006	0.026	-10000	0	-10000	0	0
IRF7	-0.002	0.028	-10000	0	-0.32	2	2
ESR1	-0.039	0.14	-10000	0	-0.44	24	24
HNF4A	-0.37	0.4	-10000	0	-0.8	119	119
MEF2C	-0.044	0.061	-10000	0	-10000	0	0
SMAD2-3/SMAD4	0.004	0.026	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.002	0.01	-10000	0	-10000	0	0
IGHV3OR16-13	-0.01	0.016	-10000	0	-10000	0	0
TGIF2/HDAC complex	0	0	-10000	0	-10000	0	0
CREBBP	0.007	0.007	-10000	0	-10000	0	0
SKIL	-0.001	0.02	-10000	0	-0.32	1	1
HDAC1	0	0.001	-10000	0	-10000	0	0
HDAC2	0	0.001	-10000	0	-10000	0	0
SNIP1	0	0.001	-10000	0	-10000	0	0
GCN5L2	0.003	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.009	0.028	-10000	0	-10000	0	0
MSG1/HSC70	-0.026	0.069	-10000	0	-10000	0	0
SMAD2	-0.001	0.007	-10000	0	-10000	0	0
SMAD3	0.013	0.029	-10000	0	-0.33	1	1
SMAD3/E2F4-5/DP1/p107/SMAD4	0	0.039	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.011	0.01	-10000	0	-10000	0	0
NCOR1	0	0.001	-10000	0	-10000	0	0
NCOA2	-0.021	0.096	-10000	0	-0.39	14	14
NCOA1	0	0	-10000	0	-10000	0	0
MYOD/E2A	-0.034	0.077	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.003	0.025	-10000	0	-10000	0	0
IFNB1	0.024	0.029	-10000	0	-10000	0	0
SMAD3/SMAD4/MEF2C	-0.03	0.064	-10000	0	-10000	0	0
CITED1	-0.04	0.11	-10000	0	-10000	0	0
SMAD2-3/SMAD4/ARC105	0.006	0.024	-10000	0	-10000	0	0
RBL1	-0.015	0.068	-10000	0	-0.32	12	12
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.004	0.041	-10000	0	-0.47	1	1
RUNX1-3/PEBPB2	-0.057	0.084	-10000	0	-0.34	4	4
SMAD7	-0.01	0.074	-10000	0	-10000	0	0
MYC/MIZ-1	0.001	0.041	-10000	0	-0.61	1	1
SMAD3/SMAD4	0.037	0.063	-10000	0	-0.41	1	1
IL10	-0.039	0.17	-10000	0	-0.5	27	27
PIASy/HDAC complex	0.001	0.005	-10000	0	-10000	0	0
PIAS3	0	0.001	-10000	0	-10000	0	0
CDK2	0.006	0.022	-10000	0	-0.32	1	1
IL5	-0.023	0.16	-10000	0	-0.51	10	10
CDK4	-0.043	0.12	-10000	0	-0.31	41	41
PIAS4	0.001	0.005	-10000	0	-10000	0	0
ATF3	-0.022	0.13	-10000	0	-0.8	7	7
SMAD3/SMAD4/SP1	-0.011	0.028	-10000	0	-10000	0	0
FOXG1	-0.094	0.15	-10000	0	-0.32	75	75
FOXO3	0.019	0.017	-10000	0	-10000	0	0
FOXO1	0.02	0.009	-10000	0	-10000	0	0
FOXO4	0.02	0.009	-10000	0	-10000	0	0
heart looping	-0.044	0.061	-10000	0	-10000	0	0
CEBPB	-0.001	0.02	-10000	0	-0.32	1	1
SMAD3/SMAD4/DLX1	-0.057	0.088	-10000	0	-10000	0	0
MYOD1	-0.05	0.12	-10000	0	-0.32	40	40
SMAD3/SMAD4/HNF4	-0.25	0.28	-10000	0	-0.55	119	119
SMAD3/SMAD4/GATA3	-0.049	0.17	-10000	0	-0.55	25	25
SnoN/SIN3/HDAC complex/NCoR1	-0.001	0.02	-10000	0	-0.32	1	1
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.038	0.07	-10000	0	-10000	0	0
SMAD3/SMAD4/SP1-3	0.004	0.025	-10000	0	-10000	0	0
MED15	0	0	-10000	0	-10000	0	0
SP1	-0.009	0.019	-10000	0	-10000	0	0
SIN3B	0	0.001	-10000	0	-10000	0	0
SIN3A	0	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.051	0.072	-10000	0	-10000	0	0
ITGB5	-0.004	0.017	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0	0.003	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.029	0.12	-10000	0	-0.54	10	10
AR	-0.057	0.17	-10000	0	-0.47	31	31
negative regulation of cell growth	-0.001	0.046	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	-0.024	0.069	-10000	0	-10000	0	0
E2F5	-0.009	0.085	-10000	0	-0.8	3	3
E2F4	0	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.003	0.016	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4	0.006	0.03	-10000	0	-10000	0	0
TFDP1	-0.002	0.028	-10000	0	-0.32	2	2
SMAD3/SMAD4/AP1	-0.015	0.11	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX2	-0.066	0.089	-10000	0	-10000	0	0
TGIF2	0	0	-10000	0	-10000	0	0
TGIF1	0	0	-10000	0	-10000	0	0
ATF2	0	0	-10000	0	-10000	0	0

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0	0	-9999	-10000	0	0
SPHK1	-0.083	0.14	-9999	-0.32	67	67
GNAI2	0	0	-9999	-10000	0	0
mol:S1P	-0.017	0.028	-9999	-10000	0	0
GNAO1	-0.1	0.27	-9999	-0.78	34	34
mol:Sphinganine-1-P	-0.04	0.1	-9999	-10000	0	0
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	-0.006	0.012	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
S1PR3	-0.004	0.053	-9999	-0.56	2	2
S1PR2	-0.001	0.02	-9999	-0.32	1	1
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.014	0.023	-9999	-10000	0	0
S1PR5	-0.016	0.07	-9999	-0.32	13	13
S1PR4	-0.006	0.044	-9999	-0.32	5	5
GNAI1	-0.012	0.098	-9999	-0.8	4	4
S1P/S1P5/G12	-0.016	0.036	-9999	-10000	0	0
S1P/S1P3/Gq	-0.025	0.097	-9999	-0.4	10	10
S1P/S1P4/Gi	-0.067	0.15	-9999	-0.38	40	40
GNAQ	0	0	-9999	-10000	0	0
GNAZ	-0.052	0.2	-9999	-0.8	17	17
GNA14	-0.049	0.19	-9999	-0.8	16	16
GNA15	-0.006	0.044	-9999	-0.32	5	5
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
GNA11	-0.003	0.049	-9999	-0.8	1	1
ABCC1	0	0	-9999	-10000	0	0

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.001	0.02	-9999	-0.32	1	1
alphaV beta3 Integrin	-0.012	0.084	-9999	-0.61	5	5
PTK2	-0.017	0.1	-9999	-0.6	6	6
positive regulation of JNK cascade	-0.009	0.053	-9999	-0.35	6	6
CDC42/GDP	-0.012	0.073	-9999	-0.48	6	6
Rac1/GDP	0.034	0.079	-9999	-0.47	6	6
RAP1B	-0.002	0.028	-9999	-0.32	2	2
RAP1A	0	0	-9999	-10000	0	0
CTNNB1	0	0	-9999	-10000	0	0
CDC42/GTP	-0.011	0.066	-9999	-0.43	6	6
nectin-3/I-afadin	-0.016	0.11	-9999	-0.69	6	6
RAPGEF1	0.032	0.091	-9999	-0.54	6	6
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.025	0.11	-9999	-0.64	6	6
PDGFB-D/PDGFRB	-0.001	0.02	-9999	-0.32	1	1
TLN1	-0.006	0.038	-9999	-0.34	1	1
Rap1/GTP	-0.01	0.057	-9999	-0.37	6	6
IQGAP1	0	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	-0.003	0.033	-9999	-0.48	1	1
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.016	0.11	-9999	-0.69	6	6
PVR	0	0	-9999	-10000	0	0
Necl-5(dimer)	0	0	-9999	-10000	0	0
mol:GDP	0.032	0.1	-9999	-0.6	6	6
MLLT4	-0.003	0.049	-9999	-0.8	1	1
PIK3CA	0	0	-9999	-10000	0	0
PI3K	-0.015	0.087	-9999	-0.51	7	7
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.002	0.038	-9999	-0.61	1	1
positive regulation of lamellipodium assembly	-0.009	0.056	-9999	-0.36	6	6
PVRL1	0	0	-9999	-10000	0	0
PVRL3	-0.019	0.12	-9999	-0.8	6	6
PVRL2	0	0	-9999	-10000	0	0
PIK3R1	-0.004	0.053	-9999	-0.56	2	2
CDH1	-0.34	0.39	-9999	-0.79	113	113
CLDN1	-0.054	0.18	-9999	-0.58	24	24
JAM-A/CLDN1	-0.043	0.15	-9999	-0.53	18	18
SRC	-0.018	0.12	-9999	-0.74	6	6
ITGB3	-0.015	0.11	-9999	-0.8	5	5
nectin-1(dimer)/I-afadin/I-afadin	-0.002	0.038	-9999	-0.61	1	1
FARP2	0.026	0.098	-9999	-0.59	6	6
RAC1	0	0	-9999	-10000	0	0
CTNNA1	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.014	0.095	-9999	-0.6	6	6
nectin-1/I-afadin	-0.002	0.038	-9999	-0.61	1	1
nectin-2/I-afadin	-0.002	0.038	-9999	-0.61	1	1
RAC1/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.014	0.095	-9999	-0.6	6	6
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.009	0.053	-9999	-0.35	6	6
alphaV/beta3 Integrin/Talin	-0.013	0.073	-9999	-0.48	5	5
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.002	0.038	-9999	-0.61	1	1
nectin-2(dimer)/I-afadin/I-afadin	-0.002	0.038	-9999	-0.61	1	1
PIP5K1C	-0.006	0.042	-9999	-0.37	1	1
VAV2	0.025	0.099	-9999	-0.6	6	6
RAP1/GDP	-0.011	0.067	-9999	-0.44	6	6
ITGAV	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.014	0.095	-9999	-0.6	6	6
nectin-3(dimer)/I-afadin/I-afadin	-0.016	0.11	-9999	-0.69	6	6
Rac1/GTP	-0.011	0.069	-9999	-0.45	6	6
PTPRM	-0.007	0.047	-9999	-0.31	6	6
E-cadherin/beta catenin/alpha catenin	-0.18	0.21	-9999	-0.42	112	112
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0	0	-9999	-10000	0	0
EPHB2	-0.043	0.11	-9999	-0.32	35	35
EFNB1	0.016	0.024	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
Rac1/GDP	-0.031	0.058	-9999	-0.39	1	1
Ephrin B2/EPHB1-2	-0.035	0.067	-9999	-0.3	4	4
neuron projection morphogenesis	-0.029	0.056	-9999	-0.37	1	1
Ephrin B1/EPHB1-2/Tiam1	-0.035	0.065	-9999	-0.42	1	1
DNM1	-0.004	0.034	-9999	-0.32	3	3
cell-cell signaling	0	0.001	-9999	-10000	0	0
MAP2K4	-0.019	0.17	-9999	-0.71	14	14
YES1	-0.05	0.22	-9999	-0.96	14	14
Ephrin B1/EPHB1-2/NCK2	-0.031	0.058	-9999	-10000	0	0
PI3K	-0.041	0.16	-9999	-0.7	15	15
mol:GDP	-0.034	0.065	-9999	-0.42	1	1
ITGA2B	-0.007	0.048	-9999	-0.32	6	6
endothelial cell proliferation	0	0	-9999	-10000	0	0
FYN	-0.05	0.22	-9999	-0.96	14	14
MAP3K7	-0.038	0.17	-9999	-0.76	14	14
FGR	-0.05	0.22	-9999	-0.96	14	14
TIAM1	-0.01	0.056	-9999	-0.32	8	8
PIK3R1	-0.004	0.053	-9999	-0.56	2	2
RGS3	0	0	-9999	-10000	0	0
cell adhesion	-0.049	0.16	-9999	-0.6	20	20
LYN	-0.05	0.22	-9999	-0.96	14	14
Ephrin B1/EPHB1-2/Src Family Kinases	-0.047	0.2	-9999	-0.9	14	14
Ephrin B1/EPHB1-2	-0.044	0.18	-9999	-0.82	14	14
SRC	-0.05	0.22	-9999	-0.96	14	14
ITGB3	-0.015	0.11	-9999	-0.8	5	5
EPHB1	-0.034	0.098	-9999	-0.32	27	27
EPHB4	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
Ephrin B2/EPHB4	0	0	-9999	-10000	0	0
alphaIIb/beta3 Integrin	-0.016	0.093	-9999	-0.64	5	5
BLK	-0.05	0.22	-9999	-0.96	14	14
HCK	-0.05	0.22	-9999	-0.96	14	14
regulation of stress fiber formation	0.03	0.057	-9999	-10000	0	0
MAPK8	-0.013	0.16	-9999	-0.66	15	15
Ephrin B1/EPHB1-2/RGS3	-0.031	0.058	-9999	-10000	0	0
endothelial cell migration	-0.029	0.15	-9999	-0.65	14	14
NCK2	0	0	-9999	-10000	0	0
PTPN13	-0.045	0.21	-9999	-0.9	14	14
regulation of focal adhesion formation	0.03	0.057	-9999	-10000	0	0
chemotaxis	0.03	0.057	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
Rac1/GTP	-0.03	0.057	-9999	-0.38	1	1
angiogenesis	-0.044	0.18	-9999	-0.81	14	14
LCK	-0.051	0.22	-9999	-0.96	14	14

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	-0.4	0.67	-9999	-1.4	75	75
PLK1	-0.002	0.11	-9999	-10000	0	0
CDKN1B	0.016	0.099	-9999	-10000	0	0
FOXO3	0.026	0.083	-9999	-10000	0	0
KAT2B	0.009	0.01	-9999	-10000	0	0
FOXO1/SIRT1	-0.11	0.18	-9999	-0.39	75	75
CAT	0.032	0.077	-9999	-10000	0	0
CTNNB1	0	0	-9999	-10000	0	0
AKT1	-0.004	0.025	-9999	-10000	0	0
FOXO1	-0.1	0.21	-9999	-0.43	75	75
MAPK10	-0.12	0.22	-9999	-0.46	75	75
mol:GTP	0.002	0	-9999	-10000	0	0
FOXO4	0.006	0.11	-9999	-10000	0	0
response to oxidative stress	-0.014	0.03	-9999	-10000	0	0
FOXO3A/SIRT1	0.003	0.061	-9999	-10000	0	0
XPO1	0	0	-9999	-10000	0	0
EP300	-0.012	0.019	-9999	-10000	0	0
BCL2L11	0.02	0.017	-9999	-10000	0	0
FOXO1/SKP2	-0.12	0.18	-9999	-0.39	75	75
mol:GDP	-0.014	0.03	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
GADD45A	0.039	0.092	-9999	-1	1	1
YWHAQ	0	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.016	0.07	-9999	-10000	0	0
MST1	0	0.086	-9999	-0.78	3	3
CSNK1D	0	0	-9999	-10000	0	0
CSNK1E	0	0	-9999	-10000	0	0
FOXO4/14-3-3 family	-0.018	0.076	-9999	-0.37	2	2
YWHAB	0	0	-9999	-10000	0	0
MAPK8	0.02	0.032	-9999	-0.46	1	1
MAPK9	0.022	0.012	-9999	-10000	0	0
YWHAG	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
YWHAZ	0	0	-9999	-10000	0	0
SIRT1	0.006	0.008	-9999	-10000	0	0
SOD2	0.003	0.12	-9999	-10000	0	0
RBL2	0.036	0.07	-9999	-10000	0	0
RAL/GDP	-0.002	0.004	-9999	-10000	0	0
CHUK	0.009	0.01	-9999	-10000	0	0
Ran/GTP	0	0	-9999	-10000	0	0
CSNK1G2	0	0	-9999	-10000	0	0
RAL/GTP	0.01	0.016	-9999	-10000	0	0
CSNK1G1	0	0	-9999	-10000	0	0
FASLG	-0.007	0.068	-9999	-10000	0	0
SKP2	-0.007	0.048	-9999	-0.32	6	6
USP7	0	0	-9999	-10000	0	0
IKBKB	0.009	0.01	-9999	-10000	0	0
CCNB1	0.026	0.089	-9999	-10000	0	0
FOXO1-3a-4/beta catenin	-0.048	0.071	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.12	0.18	-9999	-0.39	75	75
CSNK1A1	0	0	-9999	-10000	0	0
SGK1	0.009	0.01	-9999	-10000	0	0
CSNK1G3	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
ZFAND5	0.015	0.098	-9999	-10000	0	0
SFN	-0.057	0.19	-9999	-0.59	25	25
CDK2	-0.023	0.038	-9999	-0.32	1	1
FOXO3A/14-3-3	0.002	0.07	-9999	-10000	0	0
CREBBP	-0.021	0.033	-9999	-10000	0	0
FBXO32	0.028	0.082	-9999	-10000	0	0
BCL6	0.036	0.07	-9999	-10000	0	0
RALB	0	0	-9999	-10000	0	0
RALA	0	0	-9999	-10000	0	0
YWHAH	0	0	-9999	-10000	0	0

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.027	0.083	-10000	0	-0.48	6	6
ER alpha/Gai/GDP/Gbeta gamma	-0.075	0.16	-10000	0	-0.4	40	40
AKT1	-0.025	0.13	-10000	0	-0.84	6	6
PIK3CA	0	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.026	0.13	-10000	0	-0.85	6	6
mol:Ca2+	-0.005	0.13	-10000	0	-0.48	16	16
IGF1R	-0.009	0.085	-10000	0	-0.8	3	3
E2/ER alpha (dimer)/Striatin	-0.026	0.091	-10000	0	-0.53	6	6
SHC1	0	0	-10000	0	-10000	0	0
apoptosis	0.001	0.13	0.8	6	-10000	0	6
RhoA/GTP	-0.017	0.064	-10000	0	-0.4	6	6
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.055	0.13	-10000	0	-0.49	13	13
regulation of stress fiber formation	-0.03	0.061	-10000	0	-10000	0	0
E2/ERA-ERB (dimer)	-0.03	0.097	-10000	0	-0.56	6	6
KRAS	0	0	-10000	0	-10000	0	0
G13/GTP	-0.023	0.083	-10000	0	-0.49	6	6
pseudopodium formation	0.03	0.061	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1	-0.025	0.09	-10000	0	-0.53	6	6
GRB2	0	0	-10000	0	-10000	0	0
GNG2	-0.007	0.048	-10000	0	-0.32	6	6
GNAO1	-0.1	0.27	-10000	0	-0.78	34	34
HRAS	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.011	0.12	-10000	0	-0.51	7	7
E2/ER beta (dimer)	-0.006	0.036	-10000	0	-10000	0	0
mol:GDP	-0.019	0.087	-10000	0	-0.57	6	6
mol:NADP	-0.011	0.12	-10000	0	-0.51	7	7
PIK3R1	-0.004	0.053	-10000	0	-0.56	2	2
mol:IP3	-0.039	0.12	-10000	0	-0.51	16	16
IGF-1R heterotetramer	-0.009	0.085	-10000	0	-0.8	3	3
PLCB1	-0.039	0.12	-10000	0	-0.51	16	16
PLCB2	-0.041	0.13	-10000	0	-0.53	16	16
IGF1	-0.02	0.1	-10000	0	-0.44	12	12
mol:L-citrulline	-0.011	0.12	-10000	0	-0.51	7	7
RHOA	0	0	-10000	0	-10000	0	0
Gai/GDP	-0.12	0.26	-10000	0	-0.76	34	34
JNK cascade	-0.006	0.035	-10000	0	-10000	0	0
BCAR1	0	0	-10000	0	-10000	0	0
ESR2	-0.009	0.052	-10000	0	-0.32	7	7
GNAQ	0	0	-10000	0	-10000	0	0
ESR1	-0.042	0.14	-10000	0	-0.44	25	25
Gq family/GDP/Gbeta gamma	-0.02	0.079	-10000	0	-0.52	1	1
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.006	0.06	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.055	0.13	-10000	0	-0.49	13	13
GNAZ	-0.052	0.2	-10000	0	-0.8	17	17
E2/ER alpha (dimer)	-0.03	0.11	-10000	0	-0.62	6	6
STRN	-0.001	0.02	-10000	0	-0.32	1	1
GNAL	-0.041	0.17	-10000	0	-0.7	15	15
PELP1	0	0	-10000	0	-10000	0	0
MAPK11	-0.005	0.03	-10000	0	-10000	0	0
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.012	0.098	-10000	0	-0.8	4	4
HBEGF	-0.07	0.16	-10000	0	-0.43	29	29
cAMP biosynthetic process	-0.045	0.12	-10000	0	-0.43	19	19
SRC	-0.04	0.16	-10000	0	-0.5	13	13
PI3K	-0.003	0.04	-10000	0	-0.61	1	1
GNB1	0	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.018	0.077	-10000	0	-0.49	6	6
SOS1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.055	0.12	-10000	0	-0.45	15	15
Gs family/GTP	-0.046	0.12	-10000	0	-0.44	19	19
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0	0	-10000	0	-10000	0	0
vasodilation	-0.01	0.11	-10000	0	-0.49	7	7
mol:DAG	-0.039	0.12	-10000	0	-0.51	16	16
Gs family/GDP/Gbeta gamma	-0.033	0.1	-10000	0	-0.39	18	18
MSN	0.03	0.065	-10000	0	-10000	0	0
Gq family/GTP	-0.042	0.13	-10000	0	-0.54	16	16
mol:PI-3-4-5-P3	-0.025	0.12	-10000	0	-0.82	6	6
NRAS	0	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.01	0.11	0.49	7	-10000	0	7
GRB2/SOS1	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.017	0.08	-10000	0	-0.53	6	6
NOS3	-0.012	0.12	-10000	0	-0.54	7	7
GNA11	-0.003	0.049	-10000	0	-0.8	1	1
MAPKKK cascade	0	0.12	-10000	0	-0.65	6	6
E2/ER alpha (dimer)/PELP1/Src	-0.058	0.14	-10000	0	-0.52	13	13
ruffle organization	0.03	0.061	-10000	0	-10000	0	0
ROCK2	-0.015	0.059	-10000	0	-0.36	6	6
GNA14	-0.049	0.19	-10000	0	-0.8	16	16
GNA15	-0.006	0.044	-10000	0	-0.32	5	5
GNA13	0	0	-10000	0	-10000	0	0
MMP9	-0.089	0.17	-10000	0	-0.47	27	27
MMP2	-0.047	0.17	-10000	0	-0.49	18	18

×

Neurotrophic factor-mediated Trk receptor signaling

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
CRKL	0	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.042	0.084	-10000	0	-0.3	1	1
NT3 (dimer)/TRKC	-0.12	0.23	-10000	0	-0.62	41	41
NT3 (dimer)/TRKB	-0.17	0.28	-10000	0	-0.61	63	63
SHC/Grb2/SOS1/GAB1/PI3K	-0.001	0.021	-10000	0	-0.33	1	1
RAPGEF1	0	0	-10000	0	-10000	0	0
BDNF	-0.014	0.1	-10000	0	-0.7	5	5
PIK3CA	0	0	-10000	0	-10000	0	0
DYNLT1	0	0	-10000	0	-10000	0	0
NTRK1	-0.03	0.13	-10000	0	-0.46	17	17
NTRK2	-0.11	0.26	-10000	0	-0.72	38	38
NTRK3	-0.047	0.16	-10000	0	-0.47	26	26
NT-4/5 (dimer)/TRKB	-0.097	0.21	-10000	0	-0.58	37	37
neuron apoptosis	0.053	0.12	0.53	8	-10000	0	8
SHC 2-3/Grb2	-0.057	0.13	-10000	0	-0.59	8	8
SHC1	0	0	-10000	0	-10000	0	0
SHC2	-0.047	0.11	-10000	0	-0.58	6	6
SHC3	-0.053	0.13	-10000	0	-0.64	8	8
STAT3 (dimer)	-0.002	0.025	-10000	0	-0.38	1	1
NT3 (dimer)/TRKA	-0.12	0.22	-10000	0	-0.57	44	44
RIN/GDP	0.002	0.071	-10000	0	-10000	0	0
GIPC1	0	0	-10000	0	-10000	0	0
KRAS	0	0	-10000	0	-10000	0	0
DNAJA3	-0.03	0.095	-10000	0	-0.37	17	17
RIN/GTP	0	0	-10000	0	-10000	0	0
CCND1	0.019	0.066	-10000	0	-1	1	1
MAGED1	0	0	-10000	0	-10000	0	0
PTPN11	0	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0	0	-10000	0	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.032	0.1	-10000	0	-0.53	8	8
TRKA/NEDD4-2	-0.029	0.11	-10000	0	-0.61	8	8
ELMO1	0	0	-10000	0	-10000	0	0
RhoG/GTP/ELMO1/DOCK1	0	0	-10000	0	-10000	0	0
NGF	-0.011	0.088	-10000	0	-0.68	4	4
HRAS	0	0	-10000	0	-10000	0	0
DOCK1	0	0	-10000	0	-10000	0	0
GAB2	-0.001	0.02	-10000	0	-0.32	1	1
RIT2	0	0	-10000	0	-10000	0	0
RIT1	0	0	-10000	0	-10000	0	0
FRS2	-0.025	0.086	-10000	0	-0.32	20	20
DNM1	-0.004	0.034	-10000	0	-0.32	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.03	0.092	-10000	0	-0.36	17	17
mol:GDP	0	0.1	-10000	0	-0.33	2	2
NGF (dimer)	-0.01	0.087	-10000	0	-0.68	4	4
RhoG/GDP	0	0	-10000	0	-10000	0	0
RIT1/GDP	0.004	0.071	-10000	0	-10000	0	0
TIAM1	-0.01	0.056	-10000	0	-0.32	8	8
PIK3R1	-0.004	0.053	-10000	0	-0.56	2	2
BDNF (dimer)/TRKB	-0.078	0.18	-10000	0	-0.53	36	36
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2	-0.015	0.049	-10000	0	-0.34	1	1
SHC/GRB2/SOS1/GAB1	0	0	-10000	0	-10000	0	0
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.11	0.27	-10000	0	-0.69	42	42
RAP1/GDP	-0.022	0.046	-10000	0	-10000	0	0
KIDINS220/CRKL	0	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.014	0.1	-10000	0	-0.7	5	5
ubiquitin-dependent protein catabolic process	-0.031	0.11	-10000	0	-0.52	11	11
Schwann cell development	-0.022	0.032	-10000	0	-10000	0	0
EHD4	0	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	-0.012	0.042	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	-0.003	0.01	-10000	0	-10000	0	0
RAP1B	-0.002	0.028	-10000	0	-0.32	2	2
RAP1A	0	0	-10000	0	-10000	0	0
CDC42/GTP	-0.13	0.21	-10000	0	-0.67	18	18
ABL1	0	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
Rap1/GTP	-0.028	0.066	-10000	0	-10000	0	0
STAT3	-0.002	0.025	-10000	0	-0.38	1	1
axon guidance	-0.13	0.2	-10000	0	-0.63	18	18
MAPK3	-0.028	0.091	-10000	0	-0.48	8	8
MAPK1	-0.028	0.091	-10000	0	-0.48	8	8
CDC42/GDP	0.004	0.071	-10000	0	-10000	0	0
NTF3	-0.11	0.27	-10000	0	-0.69	42	42
NTF4	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/FAIM	-0.025	0.097	-10000	0	-0.53	8	8
PI3K	-0.003	0.04	-10000	0	-0.61	1	1
FRS3	-0.004	0.034	-10000	0	-0.32	3	3
FAIM	0	0	-10000	0	-10000	0	0
GAB1	0	0	-10000	0	-10000	0	0
RASGRF1	-0.042	0.11	-10000	0	-0.44	13	13
SOS1	0	0	-10000	0	-10000	0	0
MCF2L	-0.1	0.2	-10000	0	-0.54	41	41
RGS19	0	0	-10000	0	-10000	0	0
CDC42	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.026	0.048	-10000	0	-10000	0	0
Rac1/GDP	0.004	0.071	-10000	0	-10000	0	0
NGF (dimer)/TRKA/GRIT	-0.025	0.098	-10000	0	-0.53	8	8
neuron projection morphogenesis	-0.001	0.096	-10000	0	-0.4	9	9
NGF (dimer)/TRKA/NEDD4-2	-0.031	0.11	-10000	0	-0.53	11	11
MAP2K1	0	0	-10000	0	-10000	0	0
NGFR	-0.045	0.16	-10000	0	-0.51	23	23
NGF (dimer)/TRKA/GIPC/GAIP	-0.013	0.058	-10000	0	-0.33	8	8
RAS family/GTP/PI3K	-0.001	0.021	-10000	0	-0.33	1	1
FRS2 family/SHP2/GRB2/SOS1	-0.011	0.037	-10000	0	-10000	0	0
NRAS	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
PRKCI	0	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
PRKCZ	-0.091	0.25	-10000	0	-0.78	30	30
MAPKKK cascade	-0.029	0.11	-10000	0	-0.6	8	8
RASA1	0	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.022	0.094	-10000	0	-0.61	5	5
SQSTM1	0	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.07	0.17	-10000	0	-0.48	36	36
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.071	0.16	-10000	0	-0.46	36	36
MATK	-0.015	0.068	-10000	0	-0.32	12	12
NEDD4L	-0.009	0.085	-10000	0	-0.8	3	3
RAS family/GDP	-0.02	0.045	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.033	0.1	-10000	0	-0.4	17	17
Rac1/GTP	-0.037	0.073	-10000	0	-0.3	5	5
FRS2 family/SHP2/CRK family	-0.011	0.037	-10000	0	-10000	0	0

×

Canonical Wnt signaling pathway

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
HDAC1	0.001	0.007	-10000	0	-10000	0	0
AES	0.001	0.006	-10000	0	-10000	0	0
FBXW11	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
LRP6/FZD1	-0.006	0.036	-10000	0	-10000	0	0
SMAD4	0	0	-10000	0	-10000	0	0
DKK2	-0.043	0.12	-10000	0	-0.35	32	32
TLE1	-0.004	0.038	-10000	0	-0.3	4	4
MACF1	0	0	-10000	0	-10000	0	0
CTNNB1	0.025	0.047	-10000	0	-10000	0	0
WIF1	-0.054	0.12	-10000	0	-0.32	43	43
beta catenin/RanBP3	-0.004	0.041	0.38	2	-10000	0	2
KREMEN2	-0.041	0.11	-10000	0	-0.32	33	33
DKK1	-0.13	0.24	-10000	0	-0.46	74	74
beta catenin/beta TrCP1	0.004	0.04	-10000	0	-10000	0	0
FZD1	-0.009	0.052	-10000	0	-0.32	7	7
AXIN2	0.016	0.028	-10000	0	-10000	0	0
AXIN1	0	0	-10000	0	-10000	0	0
RAN	0	0	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.001	0.007	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.026	0.071	-10000	0	-10000	0	0
Axin1/APC/GSK3	0.013	0.045	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin/Macf1	0.029	0.042	-10000	0	-10000	0	0
HNF1A	-0.04	0.17	-10000	0	-0.8	13	13
CTBP1	0.001	0.007	-10000	0	-10000	0	0
MYC	0.012	0.098	-10000	0	-1.5	1	1
RANBP3	0	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.045	0.097	-10000	0	-0.39	10	10
NKD1	-0.083	0.24	-10000	0	-0.72	30	30
TCF4	-0.001	0.021	-10000	0	-0.32	1	1
TCF3	-0.002	0.029	-10000	0	-0.33	2	2
WNT1/LRP6/FZD1/Axin1	-0.017	0.047	-10000	0	-10000	0	0
Ran/GTP	0	0	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	-0.012	0.063	0.44	1	-10000	0	1
LEF1	-0.025	0.087	-10000	0	-0.32	20	20
DVL1	0.007	0.017	-10000	0	-10000	0	0
CSNK2A1	0	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.039	0.077	-10000	0	-0.47	1	1
DKK1/LRP6/Kremen 2	-0.098	0.16	-10000	0	-0.53	24	24
LRP6	-0.001	0.02	-10000	0	-0.32	1	1
CSNK1A1	0.001	0.007	-10000	0	-10000	0	0
NLK	0	0	-10000	0	-10000	0	0
CCND1	0.012	0.1	-10000	0	-1.6	1	1
WNT1	-0.028	0.091	-10000	0	-0.32	23	23
GSK3A	0	0	-10000	0	-10000	0	0
GSK3B	0	0	-10000	0	-10000	0	0
FRAT1	0	0	-10000	0	-10000	0	0
PPP2R5D	0.04	0.1	0.35	25	-10000	0	25
APC	-0.015	0.041	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.011	0.035	-10000	0	-10000	0	0
CREBBP	0.001	0.007	-10000	0	-10000	0	0

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.092	0.11	-9999	-0.7	1	1
RAD9A	0	0	-9999	-10000	0	0
AP1	-0.039	0.15	-9999	-0.61	16	16
IFNAR2	0	0	-9999	-10000	0	0
AKT1	-0.012	0.047	-9999	-0.29	6	6
ER alpha/Oestrogen	-0.03	0.11	-9999	-0.31	25	25
NFX1/SIN3/HDAC complex	0	0	-9999	-10000	0	0
EGF	-0.32	0.39	-9999	-0.8	102	102
SMG5	0	0	-9999	-10000	0	0
SMG6	0	0	-9999	-10000	0	0
SP3/HDAC2	0	0	-9999	-10000	0	0
TERT/c-Abl	-0.091	0.092	-9999	-0.66	1	1
SAP18	0	0	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	-0.36	0.4	-9999	-0.8	115	115
WRN	0	0	-9999	-10000	0	0
SP1	0	0	-9999	-10000	0	0
SP3	0	0	-9999	-10000	0	0
TERF2IP	0	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.074	0.082	-9999	-0.59	1	1
Mad/Max	0	0	-9999	-10000	0	0
TERT	-0.094	0.11	-9999	-0.72	1	1
CCND1	-0.082	0.12	-9999	-1.3	1	1
MAX	0	0	-9999	-10000	0	0
RBBP7	0	0	-9999	-10000	0	0
RBBP4	0	0	-9999	-10000	0	0
TERF2	0	0	-9999	-10000	0	0
PTGES3	0	0	-9999	-10000	0	0
SIN3A	0	0	-9999	-10000	0	0
Telomerase/911	-0.003	0.006	-9999	-10000	0	0
CDKN1B	-0.037	0.065	-9999	-10000	0	0
RAD1	0	0	-9999	-10000	0	0
XRCC5	0	0	-9999	-10000	0	0
XRCC6	0	0	-9999	-10000	0	0
SAP30	0	0	-9999	-10000	0	0
TRF2/PARP2	0	0	-9999	-10000	0	0
UBE3A	0	0	-9999	-10000	0	0
JUN	-0.002	0.028	-9999	-0.32	2	2
E6	0	0	-9999	-10000	0	0
HPV-16 E6/E6AP	0	0	-9999	-10000	0	0
FOS	-0.049	0.19	-9999	-0.8	16	16
IFN-gamma/IRF1	-0.048	0.084	-9999	-10000	0	0
PARP2	0	0	-9999	-10000	0	0
BLM	-0.14	0.16	-9999	-0.32	114	114
Telomerase	0.001	0.03	-9999	-10000	0	0
IRF1	0	0	-9999	-10000	0	0
ESR1	-0.042	0.14	-9999	-0.44	25	25
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0	0	-9999	-10000	0	0
HDAC1	0	0	-9999	-10000	0	0
HDAC2	0	0	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.016	0.02	-9999	-10000	0	0
ABL1	0	0	-9999	-10000	0	0
MXD1	0	0	-9999	-10000	0	0
MRE11A	0	0	-9999	-10000	0	0
HUS1	0	0	-9999	-10000	0	0
RPS6KB1	0	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.064	0.074	-9999	-0.58	1	1
NR2F2	0	0.001	-9999	-10000	0	0
MAPK3	0.01	0.001	-9999	-10000	0	0
MAPK1	0.01	0.001	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	-0.001	0.02	-9999	-0.32	1	1
NFKB1	0	0	-9999	-10000	0	0
HNRNPC	0	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0	0	-9999	-10000	0	0
NBN	0	0	-9999	-10000	0	0
EGFR	-0.006	0.057	-9999	-0.48	3	3
mol:Oestrogen	0	0	-9999	-10000	0	0
EGF/EGFR	-0.24	0.3	-9999	-0.61	103	103
MYC	-0.003	0.049	-9999	-0.8	1	1
IL2	0.001	0.001	-9999	-10000	0	0
KU	0	0	-9999	-10000	0	0
RAD50	0	0	-9999	-10000	0	0
HSP90AA1	0	0	-9999	-10000	0	0
TGFB1	-0.001	0.02	-9999	-0.32	1	1
TRF2/BLM	-0.083	0.094	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.087	0.09	-9999	-0.65	1	1
SP1/HDAC2	0	0	-9999	-10000	0	0
PINX1	0	0	-9999	-10000	0	0
Telomerase/EST1A	-0.074	0.082	-9999	-0.59	1	1
Smad3/Myc	-0.003	0.036	-9999	-0.53	1	1
911 complex	0	0	-9999	-10000	0	0
IFNG	-0.077	0.14	-9999	-0.31	64	64
Telomerase/PinX1	-0.074	0.082	-9999	-0.59	1	1
Telomerase/AKT1/mTOR/p70S6K	-0.002	0.03	-9999	-10000	0	0
SIN3B	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
Telomerase/EST1B	-0.074	0.082	-9999	-0.59	1	1
response to DNA damage stimulus	0.002	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0	0	-9999	-10000	0	0
TRF2/WRN	0	0	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.074	0.082	-9999	-0.59	1	1
E2F1	-0.1	0.15	-9999	-0.32	84	84
ZNFX1	0	0	-9999	-10000	0	0
PIF1	-0.026	0.088	-9999	-0.32	21	21
NCL	0	0	-9999	-10000	0	0
DKC1	0	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	-0.001	0.02	-9999	-0.32	1	1
PLK4	-0.017	0.073	-9999	-0.32	14	14
regulation of centriole replication	0.005	0.053	-9999	-10000	0	0

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.032	0.065	-9999	-10000	0	0
EPHB2	-0.044	0.11	-9999	-0.32	35	35
Syndecan-2/TACI	-0.001	0.011	-9999	-10000	0	0
LAMA1	-0.035	0.14	-9999	-0.47	19	19
Syndecan-2/alpha2 ITGB1	-0.017	0.059	-9999	-0.45	3	3
HRAS	0	0	-9999	-10000	0	0
Syndecan-2/CASK	-0.001	0.011	-9999	-10000	0	0
ITGA5	-0.002	0.028	-9999	-0.32	2	2
BAX	0.032	0.033	-9999	-10000	0	0
EPB41	-0.003	0.049	-9999	-0.8	1	1
positive regulation of cell-cell adhesion	-0.001	0.009	-9999	-10000	0	0
LAMA3	-0.035	0.12	-9999	-0.38	24	24
EZR	0	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	0	0	-9999	-10000	0	0
Syndecan-2/MMP2	-0.021	0.073	-9999	-0.53	3	3
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.002	0.022	-9999	-10000	0	0
dendrite morphogenesis	-0.023	0.057	-9999	-10000	0	0
Syndecan-2/GM-CSF	-0.005	0.029	-9999	-10000	0	0
determination of left/right symmetry	0.015	0.014	-9999	-0.21	1	1
Syndecan-2/PKC delta	-0.001	0.01	-9999	-10000	0	0
GNB2L1	-0.001	0.02	-9999	-0.32	1	1
MAPK3	-0.004	0.024	-9999	-10000	0	0
MAPK1	-0.004	0.024	-9999	-10000	0	0
Syndecan-2/RACK1	-0.001	0.011	-9999	-10000	0	0
NF1	-0.003	0.049	-9999	-0.8	1	1
FGFR/FGF/Syndecan-2	0.015	0.014	-9999	-0.21	1	1
ITGA2	-0.004	0.034	-9999	-0.32	3	3
MAPK8	0.026	0.036	-9999	-0.52	1	1
Syndecan-2/alpha2/beta1 Integrin	-0.019	0.073	-9999	-0.45	6	6
Syndecan-2/Kininogen	-0.12	0.22	-9999	-0.53	60	60
ITGB1	0	0	-9999	-10000	0	0
SRC	-0.001	0.01	-9999	-10000	0	0
Syndecan-2/CASK/Protein 4.1	-0.002	0.032	-9999	-0.49	1	1
extracellular matrix organization	-0.001	0.014	-9999	-10000	0	0
actin cytoskeleton reorganization	-0.031	0.065	-9999	-10000	0	0
Syndecan-2/Caveolin-2/Ras	-0.001	0.009	-9999	-10000	0	0
Syndecan-2/Laminin alpha3	-0.02	0.072	-9999	-0.53	3	3
Syndecan-2/RasGAP	-0.001	0.01	-9999	-10000	0	0
alpha5/beta1 Integrin	-0.002	0.018	-9999	-10000	0	0
PRKCD	0	0	-9999	-10000	0	0
Syndecan-2 dimer	-0.023	0.058	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	-0.001	0.009	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
SDCBP	0	0	-9999	-10000	0	0
TNFRSF13B	0	0	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.002	0.022	-9999	-10000	0	0
Syndecan-2/Synbindin	-0.001	0.01	-9999	-10000	0	0
TGFB1	-0.001	0.02	-9999	-0.32	1	1
CASP3	-0.001	0.009	-9999	-10000	0	0
FN1	-0.06	0.12	-9999	-0.32	48	48
Syndecan-2/IL8	-0.026	0.09	-9999	-0.53	6	6
SDC2	0.015	0.014	-9999	-0.21	1	1
KNG1	-0.18	0.34	-9999	-0.8	60	60
Syndecan-2/Neurofibromin	-0.003	0.034	-9999	-0.53	1	1
TRAPPC4	0	0	-9999	-10000	0	0
CSF2	-0.009	0.052	-9999	-0.32	7	7
Syndecan-2/TGFB1	-0.001	0.015	-9999	-10000	0	0
Syndecan-2/Syntenin/PI-4-5-P2	-0.001	0.009	-9999	-10000	0	0
Syndecan-2/Ezrin	-0.001	0.009	-9999	-10000	0	0
PRKACA	-0.002	0.031	-9999	-0.48	1	1
angiogenesis	-0.026	0.09	-9999	-0.52	6	6
MMP2	-0.037	0.12	-9999	-0.38	25	25
IL8	-0.045	0.14	-9999	-0.43	27	27
calcineurin-NFAT signaling pathway	-0.001	0.011	-9999	-10000	0	0

×

Insulin-mediated glucose transport

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.15	0.16	-9999	-0.45	33	33
CaM/Ca2+	0	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
AKT2	0	0	-9999	-10000	0	0
STXBP4	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
mol:glucose	-0.14	0.2	-9999	-0.5	34	34
YWHAZ	0	0	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
YWHAQ	0	0	-9999	-10000	0	0
TBC1D4	0.019	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
YWHAH	0	0	-9999	-10000	0	0
YWHAB	0	0	-9999	-10000	0	0
SNARE/Synip	0	0	-9999	-10000	0	0
YWHAG	0	0	-9999	-10000	0	0
ASIP	-0.01	0.056	-9999	-0.32	8	8
PRKCI	0	0	-9999	-10000	0	0
AS160/CaM/Ca2+	0	0	-9999	-10000	0	0
RHOQ	0	0	-9999	-10000	0	0
GYS1	0	0	-9999	-10000	0	0
PRKCZ	-0.091	0.25	-9999	-0.78	30	30
TRIP10	0	0	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
AS160/14-3-3	-0.015	0.057	-9999	-10000	0	0
VAMP2	0	0	-9999	-10000	0	0
SLC2A4	-0.16	0.22	-9999	-0.57	34	34
STX4	0	0	-9999	-10000	0	0
GSK3B	0	0	-9999	-10000	0	0
SFN	-0.057	0.19	-9999	-0.59	25	25
LNPEP	-0.002	0.028	-9999	-0.32	2	2
YWHAE	0	0	-9999	-10000	0	0

×

Ceramide signaling 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
SPHK2	0.016	0.039	-10000	0	-0.61	1	1
MAP4K4	-0.005	0.031	-10000	0	-10000	0	0
BAG4	-0.001	0.02	-10000	0	-0.32	1	1
PKC zeta/ceramide	-0.098	0.15	-10000	0	-0.5	29	29
NFKBIA	0	0	-10000	0	-10000	0	0
BIRC3	-0.011	0.088	-10000	0	-0.68	4	4
BAX	-0.02	0.027	-10000	0	-10000	0	0
RIPK1	0	0	-10000	0	-10000	0	0
AKT1	0.035	0.025	-10000	0	-10000	0	0
BAD	-0.044	0.056	0.2	1	-10000	0	1
SMPD1	0.022	0.016	-10000	0	-10000	0	0
RB1	-0.044	0.056	0.2	1	-10000	0	1
FADD/Caspase 8	-0.003	0.027	-10000	0	-10000	0	0
MAP2K4	-0.035	0.053	-10000	0	-10000	0	0
NSMAF	0	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.036	0.055	-10000	0	-10000	0	0
EGF	-0.32	0.39	-10000	0	-0.8	102	102
mol:ceramide	-0.055	0.06	0.21	1	-10000	0	1
MADD	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.016	0.039	-10000	0	-0.61	1	1
ASAH1	0	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.043	0.056	0.2	1	-10000	0	1
cell proliferation	-0.035	0.055	-10000	0	-0.39	3	3
BID	0.009	0.033	-10000	0	-10000	0	0
MAP3K1	-0.044	0.056	0.2	1	-10000	0	1
EIF2A	-0.027	0.051	-10000	0	-10000	0	0
TRADD	0	0	-10000	0	-10000	0	0
CRADD	-0.003	0.049	-10000	0	-0.8	1	1
MAPK3	-0.024	0.052	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.024	0.052	-10000	0	-10000	0	0
Cathepsin D/ceramide	-0.045	0.054	-10000	0	-10000	0	0
FADD	-0.004	0.03	-10000	0	-10000	0	0
KSR1	-0.044	0.058	0.2	1	-0.26	1	2
MAPK8	-0.064	0.096	-10000	0	-0.3	29	29
PRKRA	-0.044	0.056	0.2	1	-10000	0	1
PDGFA	-0.003	0.049	-10000	0	-0.8	1	1
TRAF2	0	0	-10000	0	-10000	0	0
IGF1	-0.02	0.1	-10000	0	-0.44	12	12
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.055	0.06	0.21	1	-10000	0	1
CTSD	0	0	-10000	0	-10000	0	0
regulation of nitric oxide biosynthetic process	0	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.037	0.058	-10000	0	-0.42	3	3
PRKCD	0	0	-10000	0	-10000	0	0
PRKCZ	-0.091	0.25	-10000	0	-0.78	30	30
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.016	0.039	-10000	0	-0.61	1	1
RelA/NF kappa B1	0	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	-0.019	0.12	-10000	0	-0.8	6	6
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.005	0.033	-10000	0	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.006	0.032	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.016	0.039	-10000	0	-0.61	1	1
MAP2K1	-0.027	0.052	-10000	0	-10000	0	0
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
CYCS	-0.028	0.038	-10000	0	-10000	0	0
TNFRSF1A	0	0	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
TNFR1A/BAG4	-0.001	0.013	-10000	0	-10000	0	0
EIF2AK2	-0.035	0.053	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.006	0.03	-10000	0	-10000	0	0
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	-0.002	0.017	-10000	0	-10000	0	0
MAP2K2	-0.027	0.052	-10000	0	-10000	0	0
SMPD3	0.023	0.019	-10000	0	-10000	0	0
TNF	-0.011	0.059	-10000	0	-0.32	9	9
PKC zeta/PAR4	-0.082	0.22	-10000	0	-0.66	32	32
mol:PHOSPHOCHOLINE	0.1	0.14	0.27	103	-10000	0	103
NF kappa B1/RelA/I kappa B alpha	-0.061	0.17	-10000	0	-0.49	32	32
AIFM1	-0.028	0.038	0.15	1	-10000	0	1
BCL2	0	0	-10000	0	-10000	0	0

×

IL2 signaling events mediated by PI3K

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
BCL2L1	0.024	0.066	-10000	0	-0.48	1	1
UGCG	-0.004	0.062	-10000	0	-0.98	1	1
AKT1/mTOR/p70S6K/Hsp90/TERT	0.042	0.056	-10000	0	-0.4	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.012	0.063	-10000	0	-0.95	1	1
mol:DAG	0	0.003	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.012	0.05	-10000	0	-0.56	1	1
FRAP1	0.044	0.078	-10000	0	-0.53	2	2
FOXO3	0.046	0.078	-10000	0	-0.53	2	2
AKT1	0.04	0.082	-10000	0	-0.51	3	3
GAB2	-0.001	0.02	-10000	0	-0.32	1	1
SMPD1	-0.001	0.013	-10000	0	-10000	0	0
SGMS1	-0.001	0.013	-10000	0	-10000	0	0
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	0.017	0.036	-10000	0	-0.53	1	1
CALM1	0	0	-10000	0	-10000	0	0
cell proliferation	0.025	0.082	-10000	0	-1.2	1	1
EIF3A	0	0	-10000	0	-10000	0	0
PI3K	-0.003	0.04	-10000	0	-0.61	1	1
RPS6KB1	0.016	0.017	-10000	0	-10000	0	0
mol:sphingomyelin	0	0.003	-10000	0	-10000	0	0
natural killer cell activation	0.001	0.001	-10000	0	-0.011	1	1
JAK3	-0.025	0.085	-10000	0	-0.32	20	20
PIK3R1	-0.004	0.053	-10000	0	-0.56	2	2
JAK1	0	0	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
MYC	0.043	0.096	-10000	0	-0.82	2	2
MYB	0.016	0.039	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.028	0.088	-10000	0	-0.64	2	2
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.001	0.006	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.03	0.086	-10000	0	-0.62	2	2
Rac1/GDP	-0.002	0.031	-10000	0	-0.48	1	1
T cell proliferation	-0.013	0.15	-10000	0	-0.39	32	32
SHC1	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.003	0.006	-10000	0	-0.019	15	15
PRKCZ	-0.015	0.16	-10000	0	-0.4	32	32
NF kappa B1 p50/RelA	-0.012	0.049	-10000	0	-0.55	1	1
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.02	0.057	-10000	0	-0.53	1	1
HSP90AA1	0	0	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
IL2RA	-0.076	0.16	-10000	0	-0.36	54	54
IL2RB	-0.042	0.11	-10000	0	-0.32	34	34
TERT	0	0	-10000	0	-10000	0	0
E2F1	0.015	0.026	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
RPS6	0	0	-10000	0	-10000	0	0
mol:cAMP	-0.002	0.003	0.009	15	-10000	0	15
PTPN11	0	0	-10000	0	-10000	0	0
IL2RG	-0.039	0.12	-10000	0	-0.35	29	29
actin cytoskeleton organization	-0.013	0.15	-10000	0	-0.39	32	32
GRB2	0	0	-10000	0	-10000	0	0
IL2	0.003	0.001	-10000	0	-10000	0	0
PIK3CA	0	0	-10000	0	-10000	0	0
Rac1/GTP	0.022	0.032	-10000	0	-0.46	1	1
LCK	-0.039	0.11	-10000	0	-0.33	30	30
BCL2	0.049	0.065	-10000	0	-0.49	1	1

×

IL27-mediated signaling events

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
TGFB1	-0.001	0.02	-10000	0	-0.32	1	1
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	-0.004	0.059	-10000	0	-10000	0	0
IL27/IL27R/JAK1	-0.019	0.13	-10000	0	-10000	0	0
TBX21	-0.01	0.16	-10000	0	-0.5	5	5
IL12B	-0.016	0.071	-10000	0	-0.32	13	13
IL12A	0.005	0.02	-10000	0	-0.22	1	1
IL6ST	-0.037	0.11	-10000	0	-0.33	30	30
IL27RA/JAK1	0.002	0.021	-10000	0	-10000	0	0
IL27	-0.018	0.081	-10000	0	-0.33	16	16
TYK2	0.005	0.006	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.032	0.11	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.004	0.059	-10000	0	-10000	0	0
T cell proliferation during immune response	-0.004	0.059	-10000	0	-10000	0	0
MAPKKK cascade	0.004	0.059	-10000	0	-10000	0	0
STAT3	0	0	-10000	0	-10000	0	0
STAT2	-0.001	0.02	-10000	0	-0.32	1	1
STAT1	0	0.021	-10000	0	-0.32	1	1
IL12RB1	-0.026	0.088	-10000	0	-0.32	21	21
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	0.005	0.14	-10000	0	-0.52	3	3
IL27/IL27R/JAK2/TYK2	0.002	0.059	-10000	0	-10000	0	0
positive regulation of T cell mediated cytotoxicity	0.004	0.059	-10000	0	-10000	0	0
STAT1 (dimer)	0.001	0.2	0.51	25	-10000	0	25
JAK2	-0.001	0.021	-10000	0	-0.33	1	1
JAK1	0.002	0.005	-10000	0	-10000	0	0
STAT2 (dimer)	-0.018	0.038	-10000	0	-10000	0	0
T cell proliferation	-0.035	0.15	-10000	0	-0.45	21	21
IL12/IL12R/TYK2/JAK2	0	0.044	-10000	0	-10000	0	0
IL17A	-0.032	0.11	-10000	0	-10000	0	0
mast cell activation	-0.004	0.059	-10000	0	-10000	0	0
IFNG	-0.001	0.022	-10000	0	-10000	0	0
T cell differentiation	-0.003	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	-0.017	0.038	-10000	0	-10000	0	0
STAT5A (dimer)	-0.017	0.038	-10000	0	-10000	0	0
STAT4 (dimer)	-0.022	0.049	-10000	0	-10000	0	0
STAT4	-0.01	0.056	-10000	0	-0.32	8	8
T cell activation	-0.007	0.004	-10000	0	-10000	0	0
IL27R/JAK2/TYK2	-0.018	0.046	-10000	0	-10000	0	0
GATA3	-0.14	0.45	-10000	0	-1.5	25	25
IL18	-0.024	0.14	-10000	0	-0.62	13	13
positive regulation of mast cell cytokine production	-0.017	0.038	-10000	0	-10000	0	0
IL27/EBI3	-0.03	0.1	-10000	0	-0.42	10	10
IL27RA	-0.001	0.016	-10000	0	-10000	0	0
IL6	-0.085	0.24	-10000	0	-0.8	26	26
STAT5A	0	0	-10000	0	-10000	0	0
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	0	0.01	-10000	0	-10000	0	0
IL1B	-0.021	0.12	-10000	0	-0.44	16	16
EBI3	-0.029	0.097	-10000	0	-0.33	24	24
TNF	-0.001	0.042	-10000	0	-0.22	9	9

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.36	0.4	-9999	-0.8	115	115
CLTC	0.026	0	-9999	-10000	0	0
calcium ion-dependent exocytosis	0	0	-9999	-10000	0	0
Dynamin 2/GTP	0	0	-9999	-10000	0	0
EXOC4	0	0	-9999	-10000	0	0
CD59	0.024	0	-9999	-10000	0	0
CPE	-0.005	0.041	-9999	-0.53	1	1
CTNNB1	0	0	-9999	-10000	0	0
membrane fusion	0	0	-9999	-10000	0	0
CTNND1	0	0	-9999	-10000	0	0
DNM2	0	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.027	0	-9999	-10000	0	0
TSHR	-0.018	0.053	-9999	-10000	0	0
INS	0.01	0	-9999	-10000	0	0
BIN1	0	0	-9999	-10000	0	0
mol:Choline	0	0	-9999	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
membrane depolarization	0	0	-9999	-10000	0	0
ARF6	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
JUP	0.024	0	-9999	-10000	0	0
ASAP2/amphiphysin II	0	0	-9999	-10000	0	0
ARF6/GTP	0	0	-9999	-10000	0	0
CDH1	-0.1	0.14	-9999	-0.27	111	111
clathrin-independent pinocytosis	0	0	-9999	-10000	0	0
MAPK8IP3	-0.001	0.02	-9999	-0.32	1	1
positive regulation of endocytosis	0	0	-9999	-10000	0	0
EXOC2	0	0	-9999	-10000	0	0
substrate adhesion-dependent cell spreading	0	0	-9999	-10000	0	0
insulin receptor binding	0	0	-9999	-10000	0	0
SPAG9	0	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.08	0.092	-9999	-10000	0	0
positive regulation of phagocytosis	0	0	-9999	-10000	0	0
ARF6/GTP/JIP3	-0.001	0.011	-9999	-10000	0	0
ACAP1	0.002	0.007	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CHRM2	-0.033	0.1	-9999	-0.27	38	38
clathrin heavy chain/ACAP1	0.031	0	-9999	-10000	0	0
JIP4/KLC1	0	0	-9999	-10000	0	0
EXOC1	0	0	-9999	-10000	0	0
exocyst	0	0	-9999	-10000	0	0
RALA/GTP	0	0	-9999	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0	0	-9999	-10000	0	0
receptor recycling	0	0	-9999	-10000	0	0
CTNNA1	0	0	-9999	-10000	0	0
NME1	0	0	-9999	-10000	0	0
clathrin coat assembly	0.026	0	-9999	-10000	0	0
IL2RA	0.004	0.048	-9999	-0.27	5	5
VAMP3	0	0	-9999	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.18	0.2	-9999	-0.4	115	115
EXOC6	0	0	-9999	-10000	0	0
PLD1	0	0	-9999	-10000	0	0
PLD2	0	0	-9999	-10000	0	0
EXOC5	0	0	-9999	-10000	0	0
PIP5K1C	0.027	0	-9999	-10000	0	0
SDC1	0.02	0.032	-9999	-0.27	3	3
ARF6/GDP	0	0	-9999	-10000	0	0
EXOC7	0	0	-9999	-10000	0	0
E-cadherin/beta catenin	-0.082	0.094	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
endocytosis	0	0	-9999	-10000	0	0
SCAMP2	0	0	-9999	-10000	0	0
ADRB2	0.025	0.03	-9999	-10000	0	0
EXOC3	0	0	-9999	-10000	0	0
ASAP2	0	0	-9999	-10000	0	0
Dynamin 2/GDP	0	0	-9999	-10000	0	0
KLC1	0	0	-9999	-10000	0	0
AVPR2	-0.007	0.13	-9999	-0.43	22	22
RALA	0	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.072	0.083	-9999	-10000	0	0

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	-0.042	0.11	-9999	-0.32	34	34
mol:Halofuginone	0	0	-9999	-10000	0	0
ITGA1	-0.003	0.049	-9999	-0.8	1	1
CDKN1A	-0.003	0.022	-9999	-10000	0	0
PRL-3/alpha Tubulin	0	0	-9999	-10000	0	0
mol:Ca2+	-0.14	0.26	-9999	-0.6	59	59
AGT	-0.18	0.33	-9999	-0.77	59	59
CCNA2	-0.017	0.098	-9999	-0.54	4	4
TUBA1B	0	0	-9999	-10000	0	0
EGR1	0.01	0.077	-9999	-0.6	4	4
CDK2/Cyclin E1	-0.018	0.043	-9999	-10000	0	0
MAPK3	0.019	0	-9999	-10000	0	0
PRL-2 /Rab GGTase beta	0	0	-9999	-10000	0	0
MAPK1	0.019	0	-9999	-10000	0	0
PTP4A1	0.024	0.062	-9999	-0.47	4	4
PTP4A3	0	0	-9999	-10000	0	0
PTP4A2	0	0	-9999	-10000	0	0
ITGB1	0.019	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
RAC1	-0.003	0.022	-9999	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0	0	-9999	-10000	0	0
PRL-1/ATF-5	-0.012	0.059	-9999	-0.43	4	4
RABGGTA	0	0	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
RHOC	-0.003	0.022	-9999	-10000	0	0
RHOA	-0.003	0.022	-9999	-10000	0	0
cell motility	0.027	0.028	-9999	-10000	0	0
PRL-1/alpha Tubulin	-0.007	0.054	-9999	-0.43	4	4
PRL-3/alpha1 Integrin	-0.002	0.038	-9999	-0.61	1	1
ROCK1	0.027	0.028	-9999	-10000	0	0
RABGGTB	0	0	-9999	-10000	0	0
CDK2	-0.001	0.02	-9999	-0.32	1	1
mitosis	0.024	0.061	-9999	-0.46	4	4
ATF5	-0.015	0.068	-9999	-0.32	12	12

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	-0.1	0.1	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
UBE2D3	0	0	-9999	-10000	0	0
PRKDC	0	0	-9999	-10000	0	0
ATR	0	0	-9999	-10000	0	0
UBE2L3	0	0	-9999	-10000	0	0
FANCD2	-0.004	0.019	-9999	-10000	0	0
protein ubiquitination	-0.08	0.083	-9999	-10000	0	0
XRCC5	0	0	-9999	-10000	0	0
XRCC6	0	0	-9999	-10000	0	0
M/R/N Complex	0	0	-9999	-10000	0	0
MRE11A	0	0	-9999	-10000	0	0
DNA-PK	0	0	-9999	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.002	0.019	-9999	-10000	0	0
FANCF	0	0	-9999	-10000	0	0
BRCA1	-0.002	0.028	-9999	-0.32	2	2
CCNE1	-0.042	0.11	-9999	-0.32	34	34
CDK2/Cyclin E1	-0.028	0.072	-9999	-10000	0	0
FANCG	0	0	-9999	-10000	0	0
BRCA1/BACH1/BARD1	-0.1	0.11	-9999	-0.41	2	2
FANCE	-0.009	0.052	-9999	-0.32	7	7
FANCC	0	0	-9999	-10000	0	0
NBN	0	0	-9999	-10000	0	0
FANCA	-0.02	0.077	-9999	-0.32	16	16
DNA repair	-0.025	0.091	-9999	-10000	0	0
BRCA1/BARD1/ubiquitin	-0.1	0.11	-9999	-0.41	2	2
BARD1/DNA-PK	-0.069	0.069	-9999	-10000	0	0
FANCL	0	0	-9999	-10000	0	0
mRNA polyadenylation	0.1	0.1	-9999	-10000	0	0
BRCA1/BARD1/CTIP/M/R/N Complex	-0.022	0.023	-9999	-10000	0	0
BRCA1/BACH1/BARD1/TopBP1	-0.083	0.085	-9999	-0.34	2	2
BRCA1/BARD1/P53	-0.07	0.072	-9999	-10000	0	0
BARD1/CSTF1/BRCA1	-0.083	0.085	-9999	-0.34	2	2
BRCA1/BACH1	-0.002	0.028	-9999	-0.32	2	2
BARD1	-0.16	0.16	-9999	-0.32	128	128
PCNA	0	0	-9999	-10000	0	0
BRCA1/BARD1/UbcH5C	-0.083	0.085	-9999	-0.34	2	2
BRCA1/BARD1/UbcH7	-0.083	0.085	-9999	-0.34	2	2
BRCA1/BARD1/RAD51/PCNA	-0.083	0.088	-9999	-0.46	1	1
BARD1/DNA-PK/P53	-0.061	0.061	-9999	-10000	0	0
BRCA1/BARD1/Ubiquitin	-0.1	0.11	-9999	-0.41	2	2
BRCA1/BARD1/CTIP	-0.07	0.072	-9999	-10000	0	0
FA complex	-0.004	0.014	-9999	-10000	0	0
BARD1/EWS	-0.1	0.1	-9999	-10000	0	0
RBBP8	0.019	0	-9999	-10000	0	0
TP53	0	0	-9999	-10000	0	0
TOPBP1	0	0	-9999	-10000	0	0
G1/S transition of mitotic cell cycle	0.07	0.072	-9999	-10000	0	0
BRCA1/BARD1	-0.081	0.084	-9999	-10000	0	0
CSTF1	0	0	-9999	-10000	0	0
BARD1/EWS-Fli1	-0.11	0.11	-9999	-10000	0	0
CDK2	-0.001	0.02	-9999	-0.32	1	1
UniProt:Q9BZD1	0	0	-9999	-10000	0	0
RAD51	-0.026	0.088	-9999	-0.32	21	21
RAD50	0	0	-9999	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.1	0.11	-9999	-0.41	2	2
EWSR1	0	0	-9999	-10000	0	0

×

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

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.009	0.075	-9999	-0.61	4	4
CRKL	0.015	0.073	-9999	-0.33	4	4
mol:PIP3	-0.019	0.005	-9999	-10000	0	0
AKT1	0.001	0.004	-9999	-10000	0	0
PTK2B	0	0	-9999	-10000	0	0
RAPGEF1	0.021	0.069	-9999	-10000	0	0
RANBP10	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
HGF/MET/SHIP2	-0.032	0.12	-9999	-0.53	15	15
MAP3K5	0.025	0.076	-9999	-0.63	1	1
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.029	0.11	-9999	-0.48	15	15
AP1	-0.037	0.14	-9999	-0.56	16	16
mol:SU11274	0	0	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
apoptosis	-0.033	0.19	-9999	-0.76	16	16
STAT3 (dimer)	-0.018	0.073	-9999	-0.31	15	15
GAB1/CRKL/SHP2/PI3K	-0.015	0.06	-9999	-0.37	1	1
INPP5D	-0.005	0.04	-9999	-0.32	4	4
CBL/CRK	-0.015	0.06	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
PLCG1	0	0	-9999	-10000	0	0
PTEN	0	0	-9999	-10000	0	0
ELK1	-0.001	0.034	-9999	-0.27	4	4
mol:SU5416	0	0	-9999	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.011	0.045	-9999	-10000	0	0
PAK1	0.008	0.003	-9999	-10000	0	0
HGF/MET/RANBP10	-0.032	0.12	-9999	-0.53	15	15
HRAS	-0.029	0.12	-9999	-0.75	4	4
DOCK1	0.021	0.069	-9999	-0.3	4	4
GAB1	0.008	0.076	-9999	-0.3	15	15
CRK	0.015	0.073	-9999	-0.33	4	4
mol:PHA665752	0	0	-9999	-10000	0	0
mol:GDP	-0.035	0.14	-9999	-0.61	15	15
JUN	-0.002	0.028	-9999	-0.32	2	2
EntrezGene:200958	0	0	-9999	-10000	0	0
HGF/MET	-0.017	0.067	-9999	-0.28	15	15
PIK3R1	-0.004	0.053	-9999	-0.56	2	2
cell morphogenesis	0.037	0.088	-9999	-10000	0	0
GRB2/SHC	-0.014	0.057	-9999	-0.31	4	4
FOS	-0.049	0.19	-9999	-0.8	16	16
GLMN	0	0	-9999	-10000	0	0
cell motility	-0.001	0.034	-9999	-0.27	4	4
HGF/MET/MUC20	-0.033	0.13	-9999	-0.53	15	15
cell migration	-0.014	0.056	-9999	-0.3	4	4
GRB2	0	0	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
MET/RANBP10	-0.009	0.075	-9999	-0.61	4	4
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.02	0.077	-9999	-0.33	15	15
MET/MUC20	-0.01	0.076	-9999	-0.62	4	4
RAP1B	0.026	0.067	-9999	-10000	0	0
RAP1A	0.027	0.066	-9999	-10000	0	0
HGF/MET/RANBP9	-0.032	0.12	-9999	-0.53	15	15
RAF1	0.008	0.12	-9999	-0.7	4	4
STAT3	-0.019	0.074	-9999	-0.32	15	15
cell proliferation	0.019	0.11	-9999	-0.44	15	15
RPS6KB1	-0.006	0.024	-9999	-10000	0	0
MAPK3	-0.005	0.03	-9999	-0.24	4	4
MAPK1	-0.005	0.03	-9999	-0.24	4	4
RANBP9	0	0	-9999	-10000	0	0
MAPK8	0.036	0.072	-9999	-0.47	2	2
SRC	-0.018	0.071	-9999	-10000	0	0
PI3K	-0.016	0.063	-9999	-0.34	5	5
MET/Glomulin	-0.009	0.068	-9999	-0.55	4	4
SOS1	0	0	-9999	-10000	0	0
MAP2K1	0.015	0.11	-9999	-0.63	4	4
MET	-0.012	0.098	-9999	-0.8	4	4
MAP4K1	0.02	0.069	-9999	-0.3	4	4
PTK2	0	0	-9999	-10000	0	0
MAP2K2	0.015	0.11	-9999	-0.63	4	4
BAD	0.008	0.003	-9999	-10000	0	0
MAP2K4	0.031	0.07	-9999	-0.56	1	1
SHP2/GRB2/SOS1/GAB1	-0.017	0.074	-9999	-0.49	4	4
INPPL1	0	0	-9999	-10000	0	0
PXN	0	0	-9999	-10000	0	0
SH3KBP1	0	0	-9999	-10000	0	0
HGS	-0.015	0.061	-9999	-0.33	4	4
PLCgamma1/PKC	0	0	-9999	-10000	0	0
HGF	-0.038	0.16	-9999	-0.69	14	14
RASA1	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
PTPRJ	0	0	-9999	-10000	0	0
NCK/PLCgamma1	-0.015	0.061	-9999	-0.3	4	4
PDPK1	-0.008	0.004	-9999	-10000	0	0
HGF/MET/SHIP	-0.035	0.12	-9999	-0.53	15	15

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	-0.001	0.014	-9999	-10000	0	0
PRKCZ	-0.091	0.25	-9999	-0.78	30	30
MAP3K7IP2	0	0	-9999	-10000	0	0
ERC1	0	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.012	0.051	-9999	-0.41	1	1
IRAK/TOLLIP	-0.001	0.009	-9999	-10000	0	0
IKBKB	0	0	-9999	-10000	0	0
IKBKG	0	0	-9999	-10000	0	0
IL1 alpha/IL1R2	-0.066	0.13	-9999	-0.63	7	7
IL1A	-0.08	0.14	-9999	-0.32	64	64
IL1B	-0.012	0.13	-9999	-0.61	10	10
IRAK/TRAF6/p62/Atypical PKCs	-0.047	0.13	-9999	-0.41	29	29
IL1R2	-0.02	0.12	-9999	-0.73	7	7
IL1R1	-0.006	0.07	-9999	-0.8	2	2
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.01	0.054	-9999	-0.43	2	2
TOLLIP	0	0	-9999	-10000	0	0
TICAM2	-0.001	0.02	-9999	-0.32	1	1
MAP3K3	0	0	-9999	-10000	0	0
TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
IKK complex/ELKS	-0.01	0.027	-9999	-10000	0	0
JUN	0.024	0.072	-9999	-10000	0	0
MAP3K7	0	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.027	0.11	-9999	-0.5	11	11
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.04	0.077	-9999	-0.55	2	2
PIK3R1	-0.004	0.053	-9999	-0.56	2	2
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.036	0.07	-9999	-0.52	2	2
IL1 beta fragment/IL1R1/IL1RAP	-0.028	0.11	-9999	-0.52	11	11
NFKB1	0	0	-9999	-10000	0	0
MAPK8	-0.013	0.069	-9999	-0.4	8	8
IRAK1	-0.001	0.011	-9999	-10000	0	0
IL1RN/IL1R1	-0.021	0.082	-9999	-0.61	3	3
IRAK4	0	0	-9999	-10000	0	0
PRKCI	0	0	-9999	-10000	0	0
TRAF6	0	0	-9999	-10000	0	0
PI3K	-0.003	0.04	-9999	-0.61	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.014	0.062	-9999	-0.45	2	2
CHUK	0	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.028	0.11	-9999	-0.52	11	11
IL1 beta/IL1R2	-0.037	0.14	-9999	-0.57	15	15
IRAK/TRAF6/TAK1/TAB1/TAB2	0	0.007	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.023	0.097	-9999	-0.45	11	11
IRAK3	-0.005	0.04	-9999	-0.32	4	4
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.025	0.099	-9999	-0.46	11	11
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.015	0.038	-9999	-0.36	2	2
IL1 alpha/IL1R1/IL1RAP	-0.047	0.089	-9999	-0.52	3	3
RELA	0	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
SQSTM1	0	0	-9999	-10000	0	0
MYD88	0	0	-9999	-10000	0	0
IRAK/TRAF6/MEKK3	0	0.008	-9999	-10000	0	0
IL1RAP	-0.005	0.04	-9999	-0.32	4	4
UBE2N	-0.001	0.02	-9999	-0.32	1	1
IRAK/TRAF6	-0.02	0.081	-9999	-0.7	1	1
CASP1	-0.003	0.049	-9999	-0.8	1	1
IL1RN/IL1R2	-0.031	0.11	-9999	-0.61	7	7
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.026	0.1	-9999	-0.49	11	11
TMEM189-UBE2V1	0	0	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.009	0.037	-9999	-0.41	2	2
PIK3CA	0	0	-9999	-10000	0	0
IL1RN	-0.024	0.093	-9999	-0.8	1	1
TRAF6/TAK1/TAB1/TAB2	-0.001	0.008	-9999	-10000	0	0
MAP2K6	-0.012	0.07	-9999	-0.43	7	7

×

FAS signaling pathway (CD95)

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
SPTAN1	0.003	0.009	-10000	0	-10000	0	0
RFC1	0.003	0.009	-10000	0	-10000	0	0
PRKDC	0.003	0.009	-10000	0	-10000	0	0
RIPK1	0	0	-10000	0	-10000	0	0
CASP7	0.002	0.033	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1	0.007	0.072	0.24	14	-0.38	1	15
MAP2K4	0.011	0.096	-10000	0	-0.42	2	2
mol:ceramide	-0.023	0.055	-10000	0	-0.55	1	1
GSN	0.003	0.009	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 8	-0.004	0.065	0.22	10	-0.51	1	11
FAS	0	0	-10000	0	-10000	0	0
BID	0.005	0.014	-10000	0	-10000	0	0
MAP3K1	0.017	0.058	-10000	0	-0.29	1	1
MAP3K7	0	0	-10000	0	-10000	0	0
RB1	0.003	0.009	-10000	0	-10000	0	0
CFLAR	0	0	-10000	0	-10000	0	0
HGF/MET	-0.06	0.19	-10000	0	-0.6	25	25
ARHGDIB	0.003	0.009	-10000	0	-10000	0	0
FADD	0	0	-10000	0	-10000	0	0
actin filament polymerization	-0.003	0.009	-10000	0	-10000	0	0
NFKB1	-0.023	0.063	-10000	0	-0.29	1	1
MAPK8	-0.001	0.15	-10000	0	-0.44	27	27
DFFA	0.003	0.009	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.003	0.009	-10000	0	-10000	0	0
FAS/FADD/MET	-0.008	0.065	-10000	0	-0.53	4	4
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	-0.037	0.1	-10000	0	-0.32	31	31
FAF1	-0.003	0.051	-10000	0	-0.81	1	1
PARP1	0.003	0.009	-10000	0	-10000	0	0
DFFB	0.003	0.009	-10000	0	-10000	0	0
CHUK	-0.019	0.056	-10000	0	-10000	0	0
FASLG	-0.055	0.12	-10000	0	-0.32	44	44
FAS/FADD	-0.001	0.002	-10000	0	-10000	0	0
HGF	-0.038	0.16	-10000	0	-0.69	14	14
LMNA	0.004	0.01	-10000	0	-10000	0	0
CASP6	0.003	0.009	-10000	0	-10000	0	0
CASP10	0	0	-10000	0	-10000	0	0
CASP3	0.004	0.01	-10000	0	-10000	0	0
PTPN13	-0.043	0.18	-10000	0	-0.8	14	14
CASP8	0.013	0.035	-10000	0	-10000	0	0
IL6	-0.12	0.42	-10000	0	-1.4	26	26
MET	-0.012	0.098	-10000	0	-0.8	4	4
ICAD/CAD	0.004	0.012	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 10	-0.023	0.055	-10000	0	-0.56	1	1
activation of caspase activity by cytochrome c	0.005	0.014	-10000	0	-10000	0	0
PAK2	0.003	0.01	-10000	0	-10000	0	0
BCL2	0	0	-10000	0	-10000	0	0

×

Retinoic acid receptors-mediated 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
HDAC1	0	0	-10000	0	-10000	0	0
HDAC3	0	0	-10000	0	-10000	0	0
VDR	-0.058	0.2	-10000	0	-0.75	20	20
Cbp/p300/PCAF	0	0	-10000	0	-10000	0	0
EP300	0	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.03	0.038	-10000	0	-10000	0	0
KAT2B	0	0	-10000	0	-10000	0	0
MAPK14	0	0	-10000	0	-10000	0	0
AKT1	0.027	0.061	0.23	14	-0.33	2	16
RAR alpha/9cRA/Cyclin H	-0.005	0.039	-10000	0	-0.37	2	2
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.02	0.045	-10000	0	-0.26	2	2
CDC2	0	0.001	-10000	0	-10000	0	0
response to UV	0.001	0.001	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.006	0.046	-10000	0	-0.65	1	1
NCOR2	0	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	-0.045	0.16	-10000	0	-0.58	20	20
RXRs/RARs/NRIP1/9cRA	0.03	0.082	-10000	0	-0.58	3	3
NCOA2	-0.021	0.096	-10000	0	-0.39	14	14
NCOA3	0	0	-10000	0	-10000	0	0
NCOA1	0	0	-10000	0	-10000	0	0
VDR/VDR/DNA	-0.058	0.2	-10000	0	-0.75	20	20
RARG	-0.002	0.028	-10000	0	-0.32	2	2
RAR gamma1/9cRA	-0.001	0.015	-10000	0	-10000	0	0
MAPK3	0	0	-10000	0	-10000	0	0
MAPK1	0	0	-10000	0	-10000	0	0
MAPK8	-0.003	0.049	-10000	0	-0.8	1	1
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.042	0.12	-10000	0	-0.45	20	20
RARA	-0.006	0.034	-10000	0	-0.3	3	3
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.015	0.054	-10000	0	-0.28	7	7
PRKCA	-0.006	0.07	-10000	0	-0.8	2	2
RXRs/RARs/NRIP1/9cRA/HDAC1	0.021	0.082	-10000	0	-0.59	3	3
RXRG	-0.015	0.1	-10000	0	-0.42	13	13
RXRA	0.023	0.041	-10000	0	-0.31	3	3
RXRB	0.013	0.047	-10000	0	-0.43	2	2
VDR/Vit D3/DNA	-0.045	0.16	-10000	0	-0.58	20	20
RBP1	-0.054	0.2	-10000	0	-0.77	18	18
CRBP1/9-cic-RA	-0.041	0.15	-10000	0	-0.59	18	18
RARB	-0.015	0.11	-10000	0	-0.8	5	5
PRKCG	-0.017	0.073	-10000	0	-0.32	14	14
MNAT1	0	0	-10000	0	-10000	0	0
RAR alpha/RXRs	0	0.082	-10000	0	-0.53	3	3
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.032	0.068	-10000	0	-0.47	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.031	0.044	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC3	0.021	0.082	-10000	0	-0.59	3	3
positive regulation of DNA binding	-0.004	0.037	-10000	0	-0.35	2	2
NRIP1	0.019	0.11	-10000	0	-1.4	1	1
RXRs/RARs	0.017	0.074	-10000	0	-0.52	3	3
RXRs/RXRs/DNA/9cRA	-0.014	0.062	-10000	0	-0.52	3	3
PRKACA	0	0	-10000	0	-10000	0	0
CDK7	0	0	-10000	0	-10000	0	0
TFIIH	0	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.002	0.02	-10000	0	-10000	0	0
CCNH	0	0	-10000	0	-10000	0	0
CREBBP	0	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	-0.001	0.009	-10000	0	-10000	0	0

×

Syndecan-3-mediated signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.03	0.098	-9999	-0.41	15	15
Syndecan-3/Neurocan	-0.01	0.035	-9999	-10000	0	0
POMC	-0.024	0.13	-9999	-0.69	9	9
EGFR	-0.006	0.057	-9999	-0.48	3	3
Syndecan-3/EGFR	-0.003	0.03	-9999	-0.45	1	1
AGRP	0	0	-9999	-10000	0	0
NCSTN	-0.001	0.02	-9999	-0.32	1	1
PSENEN	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0	0	-9999	-10000	0	0
APH1A	0	0	-9999	-10000	0	0
NCAN	-0.025	0.086	-9999	-0.32	20	20
long-term memory	0	0.007	-9999	-10000	0	0
Syndecan-3/IL8	-0.021	0.075	-9999	-0.45	6	6
PSEN1	0	0	-9999	-10000	0	0
Src/Cortactin	0	0	-9999	-10000	0	0
FYN	-0.001	0.02	-9999	-0.32	1	1
limb bud formation	0	0.002	-9999	-10000	0	0
MC4R	0	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
PTN	-0.064	0.2	-9999	-0.57	29	29
FGFR/FGF/Syndecan-3	0	0.002	-9999	-10000	0	0
neuron projection morphogenesis	-0.037	0.098	-9999	-0.39	15	15
Syndecan-3/AgRP	0	0.001	-9999	-10000	0	0
Syndecan-3/AgRP/MC4R	0	0.001	-9999	-10000	0	0
Fyn/Cortactin	-0.001	0.013	-9999	-10000	0	0
SDC3	0	0.002	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.021	0.074	-9999	-0.44	6	6
IL8	-0.045	0.14	-9999	-0.43	27	27
Syndecan-3/Fyn/Cortactin	0	0.007	-9999	-10000	0	0
Syndecan-3/CASK	0	0.001	-9999	-10000	0	0
alpha-MSH/MC4R	-0.018	0.1	-9999	-0.62	7	7
Gamma Secretase	0	0.008	-9999	-10000	0	0

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.051	0.12	-9999	-0.9	1	1
CRP	0.045	0.13	-9999	-0.91	1	1
cell cycle arrest	0.045	0.14	-9999	-1.1	1	1
TIMP1	0.048	0.12	-9999	-0.68	1	1
IL6ST	-0.029	0.11	-9999	-0.33	30	30
Rac1/GDP	-0.038	0.12	-9999	-0.87	3	3
AP1	0.004	0.11	-9999	-0.44	7	7
GAB2	-0.001	0.02	-9999	-0.32	1	1
TNFSF11	0.041	0.13	-9999	-0.91	1	1
HSP90B1	0.035	0.032	-9999	-10000	0	0
GAB1	0	0	-9999	-10000	0	0
MAPK14	-0.036	0.14	-9999	-0.54	10	10
AKT1	0.036	0.03	-9999	-10000	0	0
FOXO1	0.051	0.02	-9999	-10000	0	0
MAP2K6	-0.049	0.14	-9999	-0.58	10	10
mol:GTP	0.001	0.001	-9999	-10000	0	0
MAP2K4	0.022	0.13	-9999	-0.79	3	3
MITF	-0.004	0.14	-9999	-0.65	6	6
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0	0	-9999	-10000	0	0
A2M	0.017	0.004	-9999	-10000	0	0
CEBPB	0.012	0.021	-9999	-0.32	1	1
GRB2/SOS1/GAB family/SHP2	-0.01	0.042	-9999	-0.28	1	1
STAT3	0.039	0.15	-9999	-1.3	1	1
STAT1	-0.001	0.015	-9999	-10000	0	0
CEBPD	0.051	0.12	-9999	-0.9	1	1
PIK3CA	0	0	-9999	-10000	0	0
PI3K	-0.003	0.04	-9999	-0.61	1	1
JUN	-0.002	0.028	-9999	-0.32	2	2
PIAS3/MITF	-0.034	0.12	-9999	-0.75	4	4
MAPK11	-0.037	0.14	-9999	-0.7	5	5
STAT3 (dimer)/FOXO1	0.081	0.12	-9999	-0.74	1	1
GRB2/SOS1/GAB family	-0.03	0.11	-9999	-0.72	3	3
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.044	0.13	-9999	-0.61	6	6
GRB2	0	0	-9999	-10000	0	0
JAK2	-0.001	0.02	-9999	-0.32	1	1
LBP	-0.02	0.29	-9999	-0.96	20	20
PIK3R1	-0.004	0.053	-9999	-0.56	2	2
JAK1	0	0.001	-9999	-10000	0	0
MYC	0.05	0.14	-9999	-1.3	1	1
FGG	0.046	0.13	-9999	-0.9	1	1
macrophage differentiation	0.045	0.14	-9999	-1.1	1	1
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.066	0.17	-9999	-0.51	26	26
JUNB	0.049	0.12	-9999	-0.87	1	1
FOS	-0.049	0.19	-9999	-0.8	16	16
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.01	0.15	-9999	-0.49	11	11
STAT1/PIAS1	-0.03	0.12	-9999	-0.58	5	5
GRB2/SOS1/GAB family/SHP2/PI3K	0	0.018	-9999	-0.27	1	1
STAT3 (dimer)	0.034	0.14	-9999	-1.2	1	1
PRKCD	0.047	0.13	-9999	-0.85	2	2
IL6R	-0.009	0.085	-9999	-0.79	3	3
SOCS3	-0.002	0.14	-9999	-0.69	4	4
gp130 (dimer)/JAK1/JAK1/LMO4	-0.017	0.06	-9999	-0.53	1	1
Rac1/GTP	-0.036	0.12	-9999	-0.88	3	3
HCK	-0.015	0.068	-9999	-0.32	12	12
MAPKKK cascade	0.03	0.044	-9999	-10000	0	0
bone resorption	0.042	0.13	-9999	-0.85	1	1
IRF1	0.051	0.12	-9999	-0.9	1	1
mol:GDP	-0.009	0.15	-9999	-0.94	3	3
SOS1	0	0	-9999	-10000	0	0
VAV1	-0.011	0.15	-9999	-0.97	3	3
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.044	0.14	-9999	-0.84	4	4
PTPN11	-0.001	0.014	-9999	-10000	0	0
IL6/IL6RA	-0.07	0.2	-9999	-0.66	26	26
gp130 (dimer)/TYK2/TYK2/LMO4	-0.019	0.06	-9999	-0.53	1	1
gp130 (dimer)/JAK2/JAK2/LMO4	-0.019	0.061	-9999	-0.53	1	1
IL6	-0.075	0.24	-9999	-0.73	30	30
PIAS3	0	0	-9999	-10000	0	0
PTPRE	-0.001	0.029	-9999	-0.33	2	2
PIAS1	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.044	0.14	-9999	-0.39	26	26
LMO4	0.01	0.022	-9999	-0.32	1	1
STAT3 (dimer)/PIAS3	-0.028	0.11	-9999	-0.84	2	2
MCL1	0.05	0.019	-9999	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.033	0.1	-9999	-0.38	19	19
MAP3K8	-0.003	0.049	-9999	-0.8	1	1
FOS	0.015	0.089	-9999	-0.51	3	3
PRKCA	-0.006	0.07	-9999	-0.8	2	2
PTPN7	-0.013	0.092	-9999	-0.56	6	6
HRAS	0	0	-9999	-10000	0	0
PRKCB	-0.01	0.087	-9999	-0.68	4	4
NRAS	0	0	-9999	-10000	0	0
RAS family/GTP	0	0	-9999	-10000	0	0
MAPK3	0.014	0.065	-9999	-0.46	3	3
MAP2K1	0.02	0.08	-9999	-0.51	5	5
ELK1	-0.002	0.02	-9999	-0.32	1	1
BRAF	-0.012	0.072	-9999	-0.52	5	5
mol:GTP	0	0.002	-9999	-0.006	16	16
MAPK1	0.014	0.065	-9999	-0.46	3	3
RAF1	-0.012	0.072	-9999	-0.52	5	5
KRAS	0	0	-9999	-10000	0	0

×

Caspase cascade in apoptosis

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
TOP1	0.008	0.054	-10000	0	-10000	0	0
ACTA1	-0.008	0.07	-10000	0	-0.34	1	1
NUMA1	0.008	0.054	-10000	0	-10000	0	0
SPTAN1	0.004	0.064	-10000	0	-10000	0	0
LIMK1	0.002	0.065	-10000	0	-10000	0	0
BIRC3	-0.011	0.088	-10000	0	-0.68	4	4
BIRC2	-0.001	0.02	-10000	0	-0.32	1	1
BAX	0	0	-10000	0	-10000	0	0
CASP10	-0.011	0.095	-10000	0	-0.34	14	14
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	0.008	0.054	-10000	0	-10000	0	0
DIABLO	0	0	-10000	0	-10000	0	0
apoptotic nuclear changes	0.004	0.064	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
CRADD	-0.003	0.049	-10000	0	-0.8	1	1
GSN	0.004	0.064	-10000	0	-10000	0	0
MADD	0	0	-10000	0	-10000	0	0
TFAP2A	-0.045	0.18	-10000	0	-0.54	29	29
BID	-0.014	0.036	-10000	0	-10000	0	0
MAP3K1	0.005	0.029	-10000	0	-10000	0	0
TRADD	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	0.004	0.064	-10000	0	-10000	0	0
CASP9	0	0	-10000	0	-10000	0	0
DNA repair	-0.002	0.031	-10000	0	-0.22	3	3
neuron apoptosis	0.015	0.044	-10000	0	-0.68	1	1
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.009	0.061	-10000	0	-10000	0	0
APAF1	0	0	-10000	0	-10000	0	0
CASP6	0.02	0.034	-10000	0	-10000	0	0
TRAF2	0	0	-10000	0	-10000	0	0
ICAD/CAD	0.01	0.062	-10000	0	-10000	0	0
CASP7	-0.006	0.036	0.32	3	-10000	0	3
KRT18	-0.13	0.26	-10000	0	-0.61	59	59
apoptosis	0.013	0.061	-10000	0	-10000	0	0
DFFA	0.004	0.064	-10000	0	-10000	0	0
DFFB	0.004	0.064	-10000	0	-10000	0	0
PARP1	0.002	0.031	0.22	3	-10000	0	3
actin filament polymerization	-0.009	0.061	-10000	0	-10000	0	0
TNF	-0.011	0.059	-10000	0	-0.32	9	9
CYCS	0.005	0.038	-10000	0	-10000	0	0
SATB1	0.016	0.073	-10000	0	-0.42	5	5
SLK	0.004	0.064	-10000	0	-10000	0	0
p15 BID/BAX	-0.011	0.03	-10000	0	-10000	0	0
CASP2	-0.004	0.026	-10000	0	-10000	0	0
JNK cascade	-0.005	0.028	-10000	0	-10000	0	0
CASP3	-0.004	0.068	-10000	0	-10000	0	0
LMNB2	0.034	0.022	-10000	0	-10000	0	0
RIPK1	0	0	-10000	0	-10000	0	0
CASP4	0	0	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	-0.007	0.054	-10000	0	-0.48	3	3
negative regulation of DNA binding	-0.044	0.17	-10000	0	-0.53	29	29
stress fiber formation	0.004	0.064	-10000	0	-10000	0	0
GZMB	-0.026	0.11	-10000	0	-0.41	14	14
CASP1	-0.002	0.027	-10000	0	-0.44	1	1
LMNB1	0.036	0.023	-10000	0	-10000	0	0
APP	0.015	0.045	-10000	0	-0.69	1	1
TNFRSF1A	0	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.009	0	-10000	0	-10000	0	0
VIM	0.008	0.061	-10000	0	-10000	0	0
LMNA	0.034	0.022	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.004	0.028	-10000	0	-10000	0	0
LRDD	0	0	-10000	0	-10000	0	0
SREBF1	0.003	0.065	-10000	0	-10000	0	0
APAF-1/Caspase 9	-0.002	0.025	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0.008	0.054	-10000	0	-10000	0	0
CFL2	0.009	0.062	-10000	0	-10000	0	0
GAS2	-0.044	0.15	-10000	0	-0.49	23	23
positive regulation of apoptosis	0.037	0.023	-10000	0	-10000	0	0
PRF1	-0.037	0.1	-10000	0	-0.32	30	30

×

JNK signaling in the CD4+ TCR pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.024	0.087	-9999	-0.53	4	4
MAP4K1	-0.025	0.086	-9999	-0.32	20	20
MAP3K8	-0.003	0.049	-9999	-0.8	1	1
PRKCB	-0.011	0.088	-9999	-0.68	4	4
DBNL	0	0	-9999	-10000	0	0
CRKL	0	0	-9999	-10000	0	0
MAP3K1	-0.006	0.025	-9999	-10000	0	0
JUN	0.019	0.073	-9999	-0.55	4	4
MAP3K7	-0.006	0.025	-9999	-10000	0	0
GRAP2	-0.011	0.059	-9999	-0.32	9	9
CRK	0	0	-9999	-10000	0	0
MAP2K4	0.036	0.034	-9999	-10000	0	0
LAT	-0.012	0.062	-9999	-0.32	10	10
LCP2	-0.004	0.034	-9999	-10000	0	0
MAPK8	0.014	0.076	-9999	-0.59	4	4
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.007	0.028	-9999	-10000	0	0
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.022	0.08	-9999	-0.5	4	4

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	-0.001	0.02	-9999	-0.32	1	1
ANTXR2	0	0	-9999	-10000	0	0
negative regulation of myeloid dendritic cell antigen processing and presentation	0	0.002	-9999	-10000	0	0
monocyte activation	-0.037	0.12	-9999	-0.46	21	21
MAP2K2	0	0.001	-9999	-10000	0	0
MAP2K1	0	0.002	-9999	-10000	0	0
MAP2K7	0	0.002	-9999	-10000	0	0
MAP2K6	-0.013	0.077	-9999	-0.47	7	7
CYAA	-0.001	0.009	-9999	-10000	0	0
MAP2K4	0	0.002	-9999	-10000	0	0
IL1B	-0.005	0.09	-9999	-0.43	10	10
Channel	-0.001	0.01	-9999	-10000	0	0
NLRP1	0	0.002	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
negative regulation of phagocytosis	0	0.003	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
regulation of endothelial cell proliferation	0	0.002	-9999	-10000	0	0
MAPK3	0	0.002	-9999	-10000	0	0
MAPK1	0	0.002	-9999	-10000	0	0
PGR	-0.11	0.19	-9999	-0.47	55	55
PA/Cellular Receptors	-0.001	0.011	-9999	-10000	0	0
apoptosis	0	0.002	-9999	-10000	0	0
LOC728358	0	0	-9999	-10000	0	0
Lethal toxin (unfolded)	-0.001	0.008	-9999	-10000	0	0
macrophage activation	0.018	0.002	-9999	-10000	0	0
TNF	-0.011	0.059	-9999	-0.32	9	9
VCAM1	-0.038	0.13	-9999	-0.46	21	21
platelet activation	0	0.003	-9999	-10000	0	0
MAPKKK cascade	-0.012	0.018	-9999	-10000	0	0
IL18	-0.008	0.1	-9999	-0.46	13	13
negative regulation of macrophage activation	0	0.002	-9999	-10000	0	0
LEF	0	0.002	-9999	-10000	0	0
CASP1	0	0.005	-9999	-10000	0	0
mol:cAMP	0	0.003	-9999	-10000	0	0
necrosis	0	0.002	-9999	-10000	0	0
intracellular pH reduction	0	0	-9999	-10000	0	0
PAGA	0	0	-9999	-10000	0	0
Edema toxin (unfolded)	-0.001	0.009	-9999	-10000	0	0
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-9999	-10000	0	0

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.001	0.038	-9999	-0.53	1	1
BIRC5	-0.16	0.16	-9999	-0.32	128	128
NFKBIA	0.004	0.02	-9999	-10000	0	0
CPEB1	-0.031	0.15	-9999	-0.8	10	10
AKT1	0.004	0.02	-9999	-10000	0	0
NDEL1	-0.001	0.02	-9999	-0.32	1	1
Aurora A/BRCA1	-0.001	0.023	-9999	-10000	0	0
NDEL1/TACC3	-0.017	0.046	-9999	-10000	0	0
GADD45A	-0.003	0.049	-9999	-0.8	1	1
GSK3B	0	0.001	-9999	-10000	0	0
PAK1/Aurora A	0.003	0.019	-9999	-10000	0	0
MDM2	-0.062	0.13	-9999	-0.32	50	50
JUB	0	0	-9999	-10000	0	0
TPX2	-0.1	0.11	-9999	-10000	0	0
TP53	-0.001	0.019	-9999	-10000	0	0
DLG7	-0.001	0.019	-9999	-10000	0	0
AURKAIP1	0	0	-9999	-10000	0	0
ARHGEF7	0	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	-0.018	0.05	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.023	-9999	-10000	0	0
AURKA	0	0.024	-9999	-10000	0	0
AURKB	-0.006	0.014	-9999	-10000	0	0
CDC25B	0.005	0.017	-9999	-10000	0	0
G2/M transition checkpoint	0	0.016	-9999	-10000	0	0
mRNA polyadenylation	-0.019	0.097	-9999	-0.49	10	10
Aurora A/CPEB	-0.019	0.097	-9999	-0.5	10	10
Aurora A/TACC1/TRAP/chTOG	-0.002	0.01	-9999	-10000	0	0
BRCA1	-0.002	0.028	-9999	-0.32	2	2
centrosome duplication	0.003	0.019	-9999	-10000	0	0
regulation of centrosome cycle	-0.017	0.046	-9999	-10000	0	0
spindle assembly	-0.002	0.01	-9999	-10000	0	0
TDRD7	0	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.066	0.07	-9999	-10000	0	0
CENPA	0	0.012	-9999	-10000	0	0
Aurora A/PP2A	0.003	0.019	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.016	0.019	-9999	-10000	0	0
negative regulation of DNA binding	-0.001	0.019	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0	0	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
Ajuba/Aurora A	0	0.016	-9999	-10000	0	0
mitotic prometaphase	-0.009	0.01	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0.024	-9999	-10000	0	0
TACC1	0	0	-9999	-10000	0	0
TACC3	-0.031	0.095	-9999	-0.32	25	25
Aurora A/Antizyme1	-0.003	0.013	-9999	-10000	0	0
Aurora A/RasGAP	0.003	0.019	-9999	-10000	0	0
OAZ1	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0	0.001	-9999	-10000	0	0
GIT1	0	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0	0	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.1	0.11	-9999	-10000	0	0
PPP2R5D	0	0	-9999	-10000	0	0
Aurora A/TPX2	-0.078	0.082	-9999	-10000	0	0
PAK1	0	0	-9999	-10000	0	0
CKAP5	0	0	-9999	-10000	0	0

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.024	0.043	-9999	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
CRKL	0	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	-0.014	0.027	-9999	-10000	0	0
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.002	0.012	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.015	0.054	-9999	-10000	0	0
CaM/Ca2+	-0.021	0.038	-9999	-10000	0	0
RAP1A	0	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.022	0.039	-9999	-10000	0	0
AKT1	-0.018	0.037	-9999	-10000	0	0
MAP2K1	0.017	0.053	-9999	-10000	0	0
MAP3K11	-0.021	0.038	-9999	-10000	0	0
IFNGR1	0	0.001	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.062	0.16	-9999	-0.53	28	28
Rap1/GTP	-0.012	0.022	-9999	-10000	0	0
CRKL/C3G	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.028	0.049	-9999	-10000	0	0
CEBPB	0.047	0.046	-9999	-10000	0	0
STAT3	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.024	0.044	-9999	-10000	0	0
STAT1	-0.021	0.04	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.077	0.14	-9999	-0.31	64	64
PIK3CA	0	0	-9999	-10000	0	0
STAT1 (dimer)/PIAS1	-0.019	0.035	-9999	-10000	0	0
CEBPB/PTGES2/Cbp/p300	0	0.004	-9999	-10000	0	0
mol:Ca2+	-0.024	0.043	-9999	-10000	0	0
MAPK3	0.03	0.046	-9999	-10000	0	0
STAT1 (dimer)	-0.018	0.071	-9999	-10000	0	0
MAPK1	0.03	0.046	-9999	-10000	0	0
JAK2	-0.001	0.021	-9999	-0.34	1	1
PIK3R1	-0.004	0.053	-9999	-0.56	2	2
JAK1	0	0.001	-9999	-10000	0	0
CAMK2D	0	0	-9999	-10000	0	0
DAPK1	0.047	0.036	-9999	-10000	0	0
SMAD7	0.03	0.044	-9999	-10000	0	0
CBL/CRKL/C3G	-0.017	0.03	-9999	-10000	0	0
PI3K	-0.021	0.042	-9999	-0.41	1	1
IFNG	-0.077	0.14	-9999	-0.32	64	64
apoptosis	0.033	0.032	-9999	-10000	0	0
CAMK2G	0	0	-9999	-10000	0	0
STAT3 (dimer)	0	0	-9999	-10000	0	0
CAMK2A	-0.086	0.25	-9999	-0.8	28	28
CAMK2B	-0.03	0.1	-9999	-0.34	23	23
FRAP1	0.019	0.053	-9999	-10000	0	0
PRKCD	-0.018	0.037	-9999	-10000	0	0
RAP1B	-0.002	0.028	-9999	-0.32	2	2
negative regulation of cell growth	-0.015	0.054	-9999	-10000	0	0
PTPN2	0	0	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
IRF1	0.042	0.047	-9999	-10000	0	0
STAT1 (dimer)/PIASy	-0.019	0.037	-9999	-10000	0	0
SOCS1	0.004	0.02	-9999	-10000	0	0
mol:GDP	-0.016	0.029	-9999	-10000	0	0
CASP1	0.029	0.049	-9999	-0.34	1	1
PTGES2	0	0	-9999	-10000	0	0
IRF9	0.039	0.023	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.02	0.041	-9999	-0.4	1	1
RAP1/GDP	-0.012	0.022	-9999	-10000	0	0
CBL	-0.021	0.038	-9999	-10000	0	0
MAP3K1	-0.021	0.038	-9999	-10000	0	0
PIAS1	0	0	-9999	-10000	0	0
PIAS4	0	0	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.015	0.054	-9999	-10000	0	0
PTPN11	-0.024	0.043	-9999	-10000	0	0
CREBBP	0	0	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	0.019	0	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0	0	-10000	0	-10000	0	0
CDKN1B	0.031	0	-10000	0	-10000	0	0
CDKN1A	0.031	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0	0	-10000	0	-10000	0	0
FOXO3	0.031	0.009	-10000	0	-10000	0	0
AKT1	0	0	-10000	0	-10000	0	0
BAD	0	0	-10000	0	-10000	0	0
AKT3	-0.002	0.027	-10000	0	-0.44	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.031	0	-10000	0	-10000	0	0
AKT1/ASK1	-0.002	0.026	-10000	0	-0.42	1	1
BAD/YWHAZ	0	0	-10000	0	-10000	0	0
RICTOR	0	0	-10000	0	-10000	0	0
RAF1	0	0	-10000	0	-10000	0	0
JNK cascade	0.002	0.025	0.4	1	-10000	0	1
TSC1	0.031	0	-10000	0	-10000	0	0
YWHAZ	0	0	-10000	0	-10000	0	0
AKT1/RAF1	0	0	-10000	0	-10000	0	0
EP300	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.031	0	-10000	0	-10000	0	0
YWHAQ	0	0	-10000	0	-10000	0	0
TBC1D4	0	0	-10000	0	-10000	0	0
MAP3K5	-0.003	0.049	-10000	0	-0.8	1	1
MAPKAP1	0	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.025	0.042	-10000	0	-10000	0	0
YWHAH	0	0	-10000	0	-10000	0	0
AKT1S1	0.031	0	-10000	0	-10000	0	0
CASP9	0.031	0	-10000	0	-10000	0	0
YWHAB	0	0	-10000	0	-10000	0	0
p27Kip1/KPNA1	0	0	-10000	0	-10000	0	0
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0	0	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0
SRC	0	0	-10000	0	-10000	0	0
AKT2/p21CIP1	0	0	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.014	0	-10000	0	-10000	0	0
CHUK	0.031	0	-10000	0	-10000	0	0
BAD/BCL-XL	0	0	-10000	0	-10000	0	0
mTORC2	0	0	-10000	0	-10000	0	0
AKT2	0	0	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.036	0.048	-10000	0	-10000	0	0
PDPK1	0	0	-10000	0	-10000	0	0
MDM2	0.002	0.059	-10000	0	-10000	0	0
MAPKKK cascade	0	0	-10000	0	-10000	0	0
MDM2/Cbp/p300	-0.019	0.039	-10000	0	-10000	0	0
TSC1/TSC2	0.037	0	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.018	0.037	-10000	0	-10000	0	0
glucose import	-0.2	0.25	-10000	0	-0.47	115	115
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.026	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.21	0.24	-10000	0	-0.48	115	115
GSK3A	0.031	0	-10000	0	-10000	0	0
FOXO1	0.031	0	-10000	0	-10000	0	0
GSK3B	0.031	0	-10000	0	-10000	0	0
SFN	-0.057	0.19	-10000	0	-0.59	25	25
G1/S transition of mitotic cell cycle	0.037	0	-10000	0	-10000	0	0
p27Kip1/14-3-3 family	-0.013	0.053	-10000	0	-10000	0	0
PRKACA	0	0	-10000	0	-10000	0	0
KPNA1	0	0	-10000	0	-10000	0	0
HSP90AA1	0	0	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
RHEB	0	0	-10000	0	-10000	0	0
CREBBP	0	0	-10000	0	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.003	0.019	-9999	-10000	0	0
CRKL	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0	0	-9999	-10000	0	0
ITGA4	-0.007	0.048	-9999	-0.32	6	6
alpha4/beta7 Integrin/MAdCAM1	-0.022	0.054	-9999	-10000	0	0
EPO	-0.004	0.034	-9999	-0.32	3	3
alpha4/beta7 Integrin	-0.006	0.036	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.005	0.031	-9999	-10000	0	0
EPO/EPOR (dimer)	-0.002	0.022	-9999	-10000	0	0
lamellipodium assembly	-0.001	0.026	-9999	-0.4	1	1
PIK3CA	0	0	-9999	-10000	0	0
PI3K	-0.003	0.04	-9999	-0.61	1	1
ARF6	0	0	-9999	-10000	0	0
JAK2	-0.003	0.013	-9999	-10000	0	0
PXN	0	0	-9999	-10000	0	0
PIK3R1	-0.004	0.053	-9999	-0.56	2	2
MADCAM1	-0.041	0.11	-9999	-0.32	33	33
cell adhesion	-0.022	0.054	-9999	-10000	0	0
CRKL/CBL	0	0	-9999	-10000	0	0
ITGB1	0	0	-9999	-10000	0	0
SRC	-0.042	0.13	-9999	-0.48	21	21
ITGB7	-0.002	0.028	-9999	-0.32	2	2
RAC1	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.047	0.14	-9999	-0.53	21	21
p130Cas/Crk/Dock1	-0.034	0.11	-9999	-10000	0	0
VCAM1	-0.065	0.22	-9999	-0.8	21	21
RHOA	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.003	0.021	-9999	-10000	0	0
BCAR1	-0.039	0.12	-9999	-0.44	21	21
EPOR	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
GIT1	0	0	-9999	-10000	0	0
Rac1/GTP	-0.001	0.027	-9999	-0.41	1	1

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	-0.015	0.11	-10000	0	-0.8	5	5
positive regulation of NF-kappaB transcription factor activity	-0.036	0.16	-10000	0	-0.68	13	13
MAP2K4	-0.006	0.042	-10000	0	-0.3	5	5
IKBKB	0	0	-10000	0	-10000	0	0
TNFRSF10B	0	0	-10000	0	-10000	0	0
TNFRSF10A	0	0	-10000	0	-10000	0	0
SMPD1	-0.006	0.04	-10000	0	-0.29	5	5
IKBKG	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	-0.033	0.16	-10000	0	-0.72	12	12
TRAIL/TRAILR2	-0.012	0.084	-10000	0	-0.61	5	5
TRAIL/TRAILR3	-0.018	0.12	-10000	0	-0.77	6	6
TRAIL/TRAILR1	-0.012	0.084	-10000	0	-0.61	5	5
TRAIL/TRAILR4	-0.036	0.16	-10000	0	-0.68	13	13
TRAIL/TRAILR1/DAP3/GTP	-0.009	0.067	-10000	0	-0.49	5	5
IKK complex	-0.004	0.026	-10000	0	-10000	0	0
RIPK1	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0	0	-10000	0	-10000	0	0
MAPK3	0.006	0.086	-10000	0	-0.61	5	5
MAP3K1	-0.006	0.045	-10000	0	-0.32	5	5
TRAILR4 (trimer)	-0.033	0.16	-10000	0	-0.72	12	12
TRADD	0	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.006	0.046	-10000	0	-0.33	5	5
CFLAR	0	0	-10000	0	-10000	0	0
MAPK1	0.006	0.086	-10000	0	-0.61	5	5
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.009	0.062	-10000	0	-0.45	5	5
mol:ceramide	-0.006	0.039	-10000	0	-0.29	5	5
FADD	0	0	-10000	0	-10000	0	0
MAPK8	0.037	0.053	-10000	0	-0.41	1	1
TRAF2	0	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	-0.009	0.085	-10000	0	-0.8	3	3
CHUK	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.01	0.073	-10000	0	-0.53	5	5
DAP3	0	0	-10000	0	-10000	0	0
CASP10	0.002	0.081	0.3	8	-0.42	5	13
JNK cascade	-0.036	0.16	-10000	0	-0.68	13	13
TRAIL (trimer)	-0.015	0.11	-10000	0	-0.8	5	5
TNFRSF10C	-0.009	0.085	-10000	0	-0.8	3	3
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.009	0.063	-10000	0	-0.46	5	5
TRAIL/TRAILR2/FADD	-0.01	0.072	-10000	0	-0.53	5	5
cell death	-0.006	0.039	-10000	0	-0.28	5	5
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.006	0.045	-10000	0	-0.33	5	5
TRAILR2 (trimer)	0	0	-10000	0	-10000	0	0
CASP8	0.003	0.02	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.009	0.062	-10000	0	-0.45	5	5

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0	0	-10000	0	-10000	0	0
NFATC1	0.006	0.11	-10000	0	-10000	0	0
NFATC2	0.003	0.066	-10000	0	-0.25	2	2
NFATC3	-0.058	0.16	-10000	0	-0.52	29	29
YWHAE	0	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.017	0.061	-10000	0	-0.32	4	4
Exportin 1/Ran/NUP214	0	0	-10000	0	-10000	0	0
mol:DAG	0	0.002	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.016	0.052	-10000	0	-0.38	2	2
BCL2/BAX	0	0	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.001	0.003	-10000	0	-10000	0	0
CaM/Ca2+	-0.001	0.003	-10000	0	-10000	0	0
BAX	0	0	-10000	0	-10000	0	0
MAPK14	0	0	-10000	0	-10000	0	0
BAD	0	0	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.01	0.05	-10000	0	-0.47	1	1
Calcineurin A alpha-beta B1/BCL2	0	0	-10000	0	-10000	0	0
FKBP8	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.01	0.049	0.46	1	-10000	0	1
KPNB1	0	0	-10000	0	-10000	0	0
KPNA2	0	0	-10000	0	-10000	0	0
XPO1	0	0	-10000	0	-10000	0	0
SFN	-0.057	0.19	-10000	0	-0.59	25	25
MAP3K8	-0.003	0.049	-10000	0	-0.8	1	1
NFAT4/CK1 alpha	-0.038	0.11	-10000	0	-0.34	29	29
MEF2D/NFAT1/Cbp/p300	-0.033	0.088	-10000	0	-0.44	3	3
CABIN1	0.017	0.061	-10000	0	-0.32	4	4
CALM1	0	0	-10000	0	-10000	0	0
RAN	0	0	-10000	0	-10000	0	0
MAP3K1	0	0	-10000	0	-10000	0	0
CAMK4	-0.022	0.082	-10000	0	-0.32	18	18
mol:Ca2+	0	0.005	-10000	0	-10000	0	0
MAPK3	0	0	-10000	0	-10000	0	0
YWHAH	0	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.011	0.056	-10000	0	-0.61	1	1
YWHAB	0	0	-10000	0	-10000	0	0
MAPK8	-0.003	0.049	-10000	0	-0.8	1	1
MAPK9	0	0	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
FKBP1A	0	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	-0.044	0.12	-10000	0	-0.39	29	29
PRKCH	0	0	-10000	0	-10000	0	0
CABIN1/Cbp/p300	-0.001	0.003	-10000	0	-10000	0	0
CASP3	0	0	-10000	0	-10000	0	0
PIM1	-0.001	0.02	-10000	0	-0.32	1	1
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0	-10000	0	-10000	0	0
apoptosis	0	0	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	-0.012	0.049	-10000	0	-10000	0	0
PRKCB	-0.011	0.088	-10000	0	-0.68	4	4
PRKCE	0	0	-10000	0	-10000	0	0
JNK2/NFAT4	-0.053	0.15	-10000	0	-0.47	29	29
BAD/BCL-XL	0	0	-10000	0	-10000	0	0
PRKCD	0	0	-10000	0	-10000	0	0
NUP214	0	0	-10000	0	-10000	0	0
PRKCZ	-0.091	0.25	-10000	0	-0.78	30	30
PRKCA	-0.006	0.07	-10000	0	-0.8	2	2
PRKCG	-0.017	0.073	-10000	0	-0.32	14	14
PRKCQ	-0.025	0.13	-10000	0	-0.65	10	10
FKBP38/BCL2	0	0	-10000	0	-10000	0	0
EP300	0	0.001	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0	0	-10000	0	-10000	0	0
NFATc/JNK1	-0.034	0.093	-10000	0	-10000	0	0
CaM/Ca2+/FKBP38	0	0	-10000	0	-10000	0	0
FKBP12/FK506	0	0	-10000	0	-10000	0	0
CSNK1A1	0	0.002	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.012	0.044	-10000	0	-10000	0	0
NFATc/ERK1	-0.032	0.09	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.016	0.052	-10000	0	-0.38	2	2
NR4A1	-0.055	0.18	-10000	0	-0.72	16	16
GSK3B	0	0	-10000	0	-10000	0	0
positive T cell selection	-0.058	0.16	-10000	0	-0.52	29	29
NFAT1/CK1 alpha	-0.016	0.038	-10000	0	-10000	0	0
RCH1/ KPNB1	0	0	-10000	0	-10000	0	0
YWHAQ	0	0	-10000	0	-10000	0	0
PRKACA	0	0	-10000	0	-10000	0	0
AKAP5	-0.017	0.081	-10000	0	-0.36	12	12
MEF2D	0	0.001	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0	0	-10000	0	-10000	0	0
NFATc/p38 alpha	-0.032	0.09	-10000	0	-10000	0	0
CREBBP	0	0.001	-10000	0	-10000	0	0
BCL2	0	0	-10000	0	-10000	0	0

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.04	0.1	-9999	-0.53	7	7
cell-cell adhesion	0.045	0.063	-9999	-10000	0	0
Ephrin B/EPHB2/RasGAP	-0.049	0.073	-9999	-10000	0	0
ITSN1	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
Ephrin B1/EPHB3	-0.012	0.052	-9999	-0.53	1	1
Ephrin B1/EPHB1	-0.018	0.053	-9999	-10000	0	0
HRAS/GDP	-0.025	0.051	-9999	-10000	0	0
Ephrin B/EPHB1/GRB7	-0.12	0.18	-9999	-0.5	44	44
Endophilin/SYNJ1	-0.046	0.069	-9999	-10000	0	0
KRAS	0	0	-9999	-10000	0	0
Ephrin B/EPHB1/Src	-0.045	0.067	-9999	-10000	0	0
endothelial cell migration	-0.002	0.029	-9999	-0.45	1	1
GRB2	0	0	-9999	-10000	0	0
GRB7	-0.14	0.3	-9999	-0.79	45	45
PAK1	-0.045	0.067	-9999	-10000	0	0
HRAS	0	0	-9999	-10000	0	0
RRAS	-0.048	0.077	-9999	-0.57	1	1
DNM1	-0.004	0.034	-9999	-0.32	3	3
cell-cell signaling	0	0	-9999	-10000	0	0
CRK	-0.042	0.063	-9999	-10000	0	0
lamellipodium assembly	-0.045	0.063	-9999	-10000	0	0
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.012	0.021	-9999	-10000	0	0
PIK3R1	-0.004	0.053	-9999	-0.56	2	2
EPHB2	-0.044	0.11	-9999	-0.32	35	35
EPHB3	-0.022	0.089	-9999	-0.35	16	16
EPHB1	-0.034	0.098	-9999	-0.32	27	27
EPHB4	0	0	-9999	-10000	0	0
mol:GDP	-0.027	0.049	-9999	-10000	0	0
Ephrin B/EPHB2	-0.052	0.077	-9999	-10000	0	0
Ephrin B/EPHB3	-0.043	0.079	-9999	-0.45	1	1
JNK cascade	-0.03	0.058	-9999	-10000	0	0
Ephrin B/EPHB1	-0.047	0.07	-9999	-10000	0	0
RAP1/GDP	-0.021	0.039	-9999	-10000	0	0
EFNB2	0	0	-9999	-10000	0	0
EFNB3	-0.082	0.14	-9999	-0.32	66	66
EFNB1	0	0	-9999	-10000	0	0
Ephrin B2/EPHB1-2	-0.035	0.069	-9999	-0.31	4	4
RAP1B	-0.002	0.028	-9999	-0.32	2	2
RAP1A	0	0	-9999	-10000	0	0
CDC42/GTP	-0.038	0.055	-9999	-10000	0	0
Rap1/GTP	-0.044	0.062	-9999	-10000	0	0
axon guidance	-0.04	0.1	-9999	-0.53	7	7
MAPK3	0.023	0.031	-9999	-10000	0	0
MAPK1	0.023	0.031	-9999	-10000	0	0
Rac1/GDP	-0.023	0.045	-9999	-10000	0	0
actin cytoskeleton reorganization	-0.025	0.044	-9999	-10000	0	0
CDC42/GDP	-0.023	0.045	-9999	-10000	0	0
PI3K	-0.002	0.029	-9999	-0.45	1	1
EFNA5	-0.027	0.14	-9999	-0.62	11	11
Ephrin B2/EPHB4	0	0	-9999	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	-0.02	0.031	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0
RAS family/GTP	-0.042	0.06	-9999	-10000	0	0
PTK2	0.011	0.02	-9999	-10000	0	0
MAP4K4	-0.03	0.058	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
KALRN	-0.004	0.034	-9999	-0.32	3	3
Intersectin/N-WASP	0	0	-9999	-10000	0	0
neuron projection morphogenesis	-0.022	0.038	-9999	-10000	0	0
MAP2K1	-0.009	0.017	-9999	-10000	0	0
WASL	0	0	-9999	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.034	0.066	-9999	-10000	0	0
cell migration	0.019	0.034	-9999	-10000	0	0
NRAS	0	0	-9999	-10000	0	0
SYNJ1	-0.047	0.07	-9999	-10000	0	0
PXN	0	0	-9999	-10000	0	0
TF	-0.056	0.076	-9999	-10000	0	0
HRAS/GTP	-0.05	0.069	-9999	-10000	0	0
Ephrin B1/EPHB1-2	-0.035	0.069	-9999	-0.31	4	4
cell adhesion mediated by integrin	0.033	0.07	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
mol:GTP	-0.055	0.076	-9999	-0.39	1	1
RAC1-CDC42/GTP	-0.052	0.077	-9999	-0.46	1	1
RASA1	0	0	-9999	-10000	0	0
RAC1-CDC42/GDP	-0.021	0.038	-9999	-10000	0	0
ruffle organization	-0.043	0.062	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
receptor internalization	-0.043	0.064	-9999	-10000	0	0
Ephrin B/EPHB2/KALRN	-0.051	0.074	-9999	-10000	0	0
ROCK1	-0.01	0.045	-9999	-0.48	1	1
RAS family/GDP	-0.024	0.041	-9999	-10000	0	0
Rac1/GTP	-0.047	0.066	-9999	-10000	0	0
Ephrin B/EPHB1/Src/Paxillin	-0.018	0.027	-9999	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.022	0.13	-9999	-0.8	7	7
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	-0.008	0.015	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
YES1	0	0	-9999	-10000	0	0
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0	0	-9999	-10000	0	0
FYN	-0.001	0.02	-9999	-0.32	1	1
MAP3K12	0	0	-9999	-10000	0	0
FGR	0	0	-9999	-10000	0	0
p38 alpha/TAB1	-0.006	0.026	-9999	-10000	0	0
PRKG1	-0.02	0.087	-9999	-0.35	15	15
DUSP8	-0.009	0.085	-9999	-0.8	3	3
PGK/cGMP/p38 alpha	-0.012	0.041	-9999	-0.32	2	2
apoptosis	-0.006	0.026	-9999	-10000	0	0
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0	0	-9999	-10000	0	0
DUSP1	0	0	-9999	-10000	0	0
PAK1	0	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0	0	-9999	-10000	0	0
TRAF6	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.03	0.055	-9999	-10000	0	0
BLK	-0.035	0.1	-9999	-0.32	28	28
HCK	-0.015	0.068	-9999	-0.32	12	12
MAP2K3	0	0	-9999	-10000	0	0
DUSP16	0	0	-9999	-10000	0	0
DUSP10	-0.004	0.034	-9999	-0.32	3	3
TRAF6/MEKK3	0	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.033	0.039	-9999	-10000	0	0
positive regulation of innate immune response	0.037	0.06	-9999	-10000	0	0
LCK	-0.039	0.11	-9999	-0.34	30	30
p38alpha-beta/MKP7	-0.01	0.044	-9999	-10000	0	0
p38alpha-beta/MKP5	-0.009	0.045	-9999	-10000	0	0
PGK/cGMP	-0.014	0.062	-9999	-0.24	15	15
PAK2	0	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.01	0.044	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0
RALB	0	0	-9999	-10000	0	0
RALA	0	0	-9999	-10000	0	0
PAK3	-0.07	0.13	-9999	-0.32	56	56

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	0.029	0.054	-9999	-0.38	2	2
IKBKB	0.017	0.037	-9999	-10000	0	0
AKT1	0.012	0.071	-9999	-0.25	5	5
IKBKG	0.02	0.038	-9999	-10000	0	0
CALM1	0.006	0.049	-9999	-0.4	3	3
PIK3CA	0	0	-9999	-10000	0	0
MAP3K1	0.024	0.072	-9999	-0.55	2	2
MAP3K7	0	0	-9999	-10000	0	0
mol:Ca2+	-0.008	0.05	-9999	-0.42	3	3
DOK1	0	0	-9999	-10000	0	0
AP-1	0.016	0.059	-9999	-0.22	1	1
LYN	0	0	-9999	-10000	0	0
BLNK	-0.006	0.07	-9999	-0.8	2	2
SHC1	0	0	-9999	-10000	0	0
BCR complex	-0.023	0.083	-9999	-0.51	4	4
CD22	-0.055	0.14	-9999	-0.48	23	23
CAMK2G	0.013	0.046	-9999	-0.36	3	3
CSNK2A1	0	0	-9999	-10000	0	0
INPP5D	-0.005	0.04	-9999	-0.32	4	4
SHC/GRB2/SOS1	-0.018	0.073	-9999	-0.78	1	1
GO:0007205	-0.001	0.052	-9999	-0.43	3	3
SYK	-0.007	0.073	-9999	-0.64	3	3
ELK1	0.006	0.05	-9999	-0.4	3	3
NFATC1	0.018	0.065	-9999	-0.45	2	2
B-cell antigen/BCR complex	-0.023	0.083	-9999	-0.51	4	4
PAG1/CSK	-0.001	0.013	-9999	-10000	0	0
NFKBIB	0.014	0.014	-9999	-10000	0	0
HRAS	0.011	0.054	-9999	-0.42	3	3
NFKBIA	0.014	0.014	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.017	0.012	-9999	-10000	0	0
RasGAP/Csk	-0.026	0.085	-9999	-0.44	8	8
mol:GDP	-0.001	0.049	-9999	-0.4	3	3
PTEN	0	0	-9999	-10000	0	0
CD79B	-0.009	0.075	-9999	-0.56	4	4
NF-kappa-B/RelA/I kappa B alpha	0.017	0.012	-9999	-10000	0	0
GRB2	0	0	-9999	-10000	0	0
PI3K/BCAP/CD19	0.01	0.091	-9999	-0.51	5	5
PIK3R1	-0.004	0.053	-9999	-0.56	2	2
mol:IP3	-0.009	0.051	-9999	-0.44	3	3
CSK	0	0	-9999	-10000	0	0
FOS	-0.014	0.11	-9999	-0.4	19	19
CHUK	0.02	0.038	-9999	-10000	0	0
IBTK	0	0	-9999	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.013	0.048	-9999	-0.43	1	1
PTPN6	-0.051	0.13	-9999	-0.45	24	24
RELA	0	0	-9999	-10000	0	0
BCL2A1	0.009	0.022	-9999	-10000	0	0
VAV2	-0.023	0.077	-9999	-0.54	3	3
ubiquitin-dependent protein catabolic process	0.017	0.014	-9999	-10000	0	0
BTK	0.001	0.029	-9999	-10000	0	0
CD19	-0.025	0.083	-9999	-0.65	2	2
MAP4K1	-0.025	0.086	-9999	-0.32	20	20
CD72	-0.058	0.12	-9999	-0.32	47	47
PAG1	-0.001	0.02	-9999	-0.32	1	1
MAPK14	0.03	0.064	-9999	-0.46	2	2
SH3BP5	0	0	-9999	-10000	0	0
PIK3AP1	0.008	0.055	-9999	-0.46	3	3
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.014	0.058	-9999	-0.56	2	2
RAF1	0.017	0.051	-9999	-0.38	3	3
RasGAP/p62DOK/SHIP	-0.026	0.084	-9999	-0.42	9	9
CD79A	-0.026	0.088	-9999	-0.32	21	21
re-entry into mitotic cell cycle	0.015	0.058	-9999	-0.23	1	1
RASA1	0	0	-9999	-10000	0	0
MAPK3	0.029	0.044	-9999	-0.41	1	1
MAPK1	0.029	0.044	-9999	-0.41	1	1
CD72/SHP1	-0.068	0.13	-9999	-0.42	25	25
NFKB1	0	0	-9999	-10000	0	0
MAPK8	0.028	0.068	-9999	-0.42	3	3
actin cytoskeleton organization	0.016	0.078	-9999	-0.53	2	2
NF-kappa-B/RelA	0.037	0.024	-9999	-10000	0	0
Calcineurin	-0.005	0.038	-9999	-0.42	1	1
PI3K	-0.046	0.11	-9999	-0.48	9	9
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.009	0.056	-9999	-0.49	3	3
SOS1	0	0	-9999	-10000	0	0
Bam32/HPK1	-0.02	0.077	-9999	-0.68	2	2
DAPP1	-0.012	0.072	-9999	-0.76	2	2
cytokine secretion	0.018	0.062	-9999	-0.42	2	2
mol:DAG	-0.009	0.051	-9999	-0.44	3	3
PLCG2	0	0	-9999	-10000	0	0
MAP2K1	0.023	0.048	-9999	-0.46	1	1
B-cell antigen/BCR complex/FcgammaRIIB	-0.032	0.1	-9999	-0.49	10	10
mol:PI-3-4-5-P3	-0.034	0.082	-9999	-0.34	8	8
ETS1	0.019	0.043	-9999	-0.42	1	1
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.022	0.086	-9999	-0.54	5	5
B-cell antigen/BCR complex/LYN	-0.018	0.07	-9999	-0.56	3	3
MALT1	0	0	-9999	-10000	0	0
TRAF6	0	0	-9999	-10000	0	0
RAC1	0.016	0.082	-9999	-0.57	2	2
B-cell antigen/BCR complex/LYN/SYK	-0.055	0.14	-9999	-0.46	24	24
CARD11	-0.005	0.063	-9999	-0.4	3	3
FCGR2B	-0.021	0.12	-9999	-0.68	8	8
PPP3CA	0	0	-9999	-10000	0	0
BCL10	0	0	-9999	-10000	0	0
IKK complex	0.017	0.02	-9999	-10000	0	0
PTPRC	-0.02	0.087	-9999	-0.35	15	15
PDPK1	-0.023	0.056	-9999	-0.27	3	3
PPP3CB	0	0	-9999	-10000	0	0
PPP3CC	0	0	-9999	-10000	0	0
POU2F2	0.016	0.011	-9999	-10000	0	0

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0	0	-10000	0	-10000	0	0
PTK2	0	0	-10000	0	-10000	0	0
CRKL	-0.013	0.077	-10000	0	-0.51	5	5
GRB2/SOS1/SHC	0	0	-10000	0	-10000	0	0
HRAS	0	0	-10000	0	-10000	0	0
IRS1/Crk	-0.013	0.077	-10000	0	-0.51	5	5
IGF-1R heterotetramer/IGF1/PTP1B	-0.016	0.088	-10000	0	-0.59	5	5
AKT1	-0.012	0.068	-10000	0	-0.55	2	2
BAD	0.032	0.071	-10000	0	-0.66	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.013	0.077	-10000	0	-0.51	5	5
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.014	0.077	-10000	0	-0.52	5	5
RAF1	0.034	0.067	-10000	0	-0.61	1	1
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.013	0.073	-10000	0	-0.49	5	5
YWHAZ	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.015	0.084	-10000	0	-0.51	6	6
PIK3CA	0	0	-10000	0	-10000	0	0
RPS6KB1	-0.012	0.068	-10000	0	-0.55	2	2
GNB2L1	-0.001	0.02	-10000	0	-0.32	1	1
positive regulation of MAPKKK cascade	0.03	0.058	-10000	0	-0.5	1	1
PXN	0	0	-10000	0	-10000	0	0
PIK3R1	-0.004	0.053	-10000	0	-0.56	2	2
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
HRAS/GTP	-0.011	0.065	-10000	0	-0.74	1	1
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.013	0.072	-10000	0	-0.48	5	5
IGF-1R heterotetramer	-0.011	0.09	-10000	0	-0.84	3	3
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.014	0.077	-10000	0	-0.52	5	5
Crk/p130 Cas/Paxillin	-0.007	0.07	-10000	0	-0.46	5	5
IGF1R	-0.011	0.09	-10000	0	-0.84	3	3
IGF1	-0.021	0.11	-10000	0	-0.45	12	12
IRS2/Crk	-0.012	0.073	-10000	0	-0.48	5	5
PI3K	-0.015	0.078	-10000	0	-0.48	6	6
apoptosis	0.01	0.053	0.54	1	-10000	0	1
HRAS/GDP	0	0	-10000	0	-10000	0	0
PRKCD	-0.011	0.077	-10000	0	-0.52	5	5
RAF1/14-3-3 E	-0.009	0.05	-10000	0	-0.51	1	1
BAD/14-3-3	-0.01	0.057	-10000	0	-0.59	1	1
PRKCZ	-0.059	0.15	-10000	0	-0.45	30	30
Crk/p130 Cas/Paxillin/FAK1	-0.01	0.056	-10000	0	-0.6	1	1
PTPN1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.012	0.082	-10000	0	-0.55	5	5
BCAR1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.014	0.078	-10000	0	-0.52	5	5
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.013	0.076	-10000	0	-0.51	5	5
GRB10	0	0	-10000	0	-10000	0	0
PTPN11	-0.013	0.077	-10000	0	-0.51	5	5
IRS1	-0.015	0.083	-10000	0	-0.51	6	6
IRS2	-0.013	0.077	-10000	0	-0.51	5	5
IGF-1R heterotetramer/IGF1	-0.021	0.11	-10000	0	-0.72	5	5
GRB2	0	0	-10000	0	-10000	0	0
PDPK1	-0.014	0.073	-10000	0	-0.45	6	6
YWHAE	0	0	-10000	0	-10000	0	0
PRKD1	-0.013	0.081	-10000	0	-0.5	6	6
SHC1	0	0	-10000	0	-10000	0	0

×

Rapid glucocorticoid 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
Gs family/GDP/Gbeta gamma	-0.026	0.099	-10000	0	-0.46	12	12
MAPK9	0	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	0	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.004	0.026	-10000	0	-10000	0	0
GNB1	0	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0	0	-10000	0	-10000	0	0
Gs family/GTP	-0.025	0.11	-10000	0	-0.5	12	12
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	0.006	0.024	0.1	15	-10000	0	15
GNAL	-0.041	0.17	-10000	0	-0.7	15	15
GNG2	-0.007	0.048	-10000	0	-0.32	6	6
CRH	0	0	-10000	0	-10000	0	0
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	-0.002	0.028	-10000	0	-0.45	1	1
MAPK11	0	0.006	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	-0.003	0.021	-10000	0	-10000	0	0
HDAC3	0	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.002	0.025	-10000	0	-0.4	1	1
GATA1/HDAC4	-0.11	0.24	-10000	0	-0.61	47	47
GATA1/HDAC5	-0.11	0.23	-10000	0	-0.61	46	46
GATA2/HDAC5	-0.006	0.056	-10000	0	-0.61	2	2
HDAC5/BCL6/BCoR	-0.001	0.01	-10000	0	-10000	0	0
HDAC9	-0.002	0.028	-10000	0	-0.32	2	2
Glucocorticoid receptor/Hsp90/HDAC6	0	0	-10000	0	-10000	0	0
HDAC4/ANKRA2	-0.002	0.038	-10000	0	-0.61	1	1
HDAC5/YWHAB	0	0	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0	0	-10000	0	-10000	0	0
GATA2	-0.009	0.075	-10000	0	-0.56	4	4
HDAC4/RFXANK	-0.002	0.038	-10000	0	-0.61	1	1
BCOR	-0.001	0.02	-10000	0	-0.32	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0	0	-10000	0	-10000	0	0
HDAC5	0	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.005	0.031	-10000	0	-10000	0	0
Histones	-0.001	0.017	-10000	0	-10000	0	0
ADRBK1	0	0	-10000	0	-10000	0	0
HDAC4	-0.003	0.049	-10000	0	-0.8	1	1
XPO1	0	0	-10000	0	-10000	0	0
HDAC5/ANKRA2	0	0	-10000	0	-10000	0	0
HDAC4/Ubc9	-0.002	0.038	-10000	0	-0.61	1	1
HDAC7	-0.001	0.02	-10000	0	-0.32	1	1
HDAC5/14-3-3 E	0	0	-10000	0	-10000	0	0
TUBA1B	0	0	-10000	0	-10000	0	0
HDAC6	0	0	-10000	0	-10000	0	0
HDAC5/RFXANK	0	0	-10000	0	-10000	0	0
CAMK4	-0.022	0.082	-10000	0	-0.32	18	18
Tubulin/HDAC6	0	0	-10000	0	-10000	0	0
SUMO1	0	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0	0	-10000	0	-10000	0	0
GATA1	-0.14	0.3	-10000	0	-0.79	47	47
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0
NR3C1	0	0	-10000	0	-10000	0	0
SUMO1/HDAC4	-0.002	0.027	-10000	0	-0.44	1	1
SRF	0	0	-10000	0	-10000	0	0
HDAC4/YWHAB	-0.002	0.038	-10000	0	-0.61	1	1
Tubulin	0	0	-10000	0	-10000	0	0
HDAC4/14-3-3 E	-0.002	0.038	-10000	0	-0.61	1	1
GNB1	0	0	-10000	0	-10000	0	0
RANGAP1	0	0	-10000	0	-10000	0	0
BCL6/BCoR	-0.001	0.013	-10000	0	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	-0.002	0.033	-10000	0	-0.53	1	1
HDAC4/SRF	-0.013	0.053	-10000	0	-0.53	1	1
HDAC4/ER alpha	-0.032	0.11	-10000	0	-0.63	7	7
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	-0.001	0.017	-10000	0	-10000	0	0
cell motility	0	0	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0	0	-10000	0	-10000	0	0
HDAC7/HDAC3	-0.001	0.013	-10000	0	-10000	0	0
BCL6	0	0	-10000	0	-10000	0	0
HDAC4/CaMK II delta B	-0.003	0.049	-10000	0	-0.8	1	1
Hsp90/HDAC6	0	0	-10000	0	-10000	0	0
ESR1	-0.042	0.14	-10000	0	-0.44	25	25
HDAC6/HDAC11	0	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0	0	-10000	0	-10000	0	0
NPC	0	0	-10000	0	-10000	0	0
MEF2C	0	0	-10000	0	-10000	0	0
RAN	0	0	-10000	0	-10000	0	0
HDAC4/MEF2C	-0.002	0.028	-10000	0	-0.45	1	1
GNG2	-0.007	0.048	-10000	0	-0.32	6	6
NCOR2	0	0	-10000	0	-10000	0	0
TUBB2A	0	0	-10000	0	-10000	0	0
HDAC11	0	0	-10000	0	-10000	0	0
HSP90AA1	0	0	-10000	0	-10000	0	0
RANBP2	0	0	-10000	0	-10000	0	0
ANKRA2	0	0	-10000	0	-10000	0	0
RFXANK	0	0	-10000	0	-10000	0	0
nuclear import	0.002	0.027	0.44	1	-10000	0	1

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0	0	-9999	-10000	0	0
HDAC2	0	0	-9999	-10000	0	0
GNB1/GNG2	-0.016	0.082	-9999	-0.52	6	6
forebrain development	-0.01	0.095	-9999	-0.4	4	4
GNAO1	-0.1	0.27	-9999	-0.78	34	34
SMO/beta Arrestin2	-0.014	0.092	-9999	-0.61	6	6
SMO	-0.019	0.12	-9999	-0.8	6	6
ARRB2	0	0	-9999	-10000	0	0
GLI3/SPOP	-0.001	0.015	-9999	-10000	0	0
mol:GTP	0	0.001	-9999	-10000	0	0
GSK3B	0	0	-9999	-10000	0	0
GNAI2	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0	0	-9999	-10000	0	0
GNAI1	-0.012	0.098	-9999	-0.8	4	4
XPO1	0.004	0.005	-9999	-10000	0	0
GLI1/Su(fu)	-0.035	0.075	-9999	-0.38	6	6
SAP30	0	0	-9999	-10000	0	0
mol:GDP	-0.018	0.12	-9999	-0.79	6	6
MIM/GLI2A	0.006	0.007	-9999	-10000	0	0
IFT88	-0.003	0.049	-9999	-0.8	1	1
GNAI3	0	0	-9999	-10000	0	0
GLI2	0.036	0.01	-9999	-10000	0	0
GLI3	0.037	0.032	-9999	-10000	0	0
CSNK1D	0	0	-9999	-10000	0	0
CSNK1E	0	0	-9999	-10000	0	0
SAP18	0	0	-9999	-10000	0	0
embryonic digit morphogenesis	-0.003	0.049	-9999	-0.8	1	1
GNG2	-0.007	0.048	-9999	-0.32	6	6
Gi family/GTP	-0.074	0.16	-9999	-0.37	51	51
SIN3B	0	0	-9999	-10000	0	0
SIN3A	0	0	-9999	-10000	0	0
GLI3/Su(fu)	0	0.018	-9999	-10000	0	0
GLI2/Su(fu)	-0.004	0.028	-9999	-10000	0	0
FOXA2	-0.018	0.051	-9999	-10000	0	0
neural tube patterning	-0.01	0.095	-9999	-0.4	4	4
SPOP	0	0	-9999	-10000	0	0
Su(fu)/PIAS1	-0.006	0.037	-9999	-10000	0	0
GNB1	0	0	-9999	-10000	0	0
CSNK1G2	0	0	-9999	-10000	0	0
CSNK1G3	0	0	-9999	-10000	0	0
MTSS1	0.006	0.007	-9999	-10000	0	0
embryonic limb morphogenesis	-0.01	0.095	-9999	-0.4	4	4
SUFU	-0.006	0.042	-9999	-0.28	6	6
LGALS3	-0.003	0.049	-9999	-0.8	1	1
catabolic process	0	0.008	-9999	-10000	0	0
GLI3A/CBP	-0.02	0.057	-9999	-0.38	3	3
KIF3A	0	0	-9999	-10000	0	0
GLI1	-0.011	0.096	-9999	-0.41	4	4
RAB23	-0.002	0.028	-9999	-0.32	2	2
CSNK1A1	0	0	-9999	-10000	0	0
IFT172	0	0	-9999	-10000	0	0
RBBP7	0	0	-9999	-10000	0	0
Su(fu)/Galectin3	-0.008	0.047	-9999	-0.48	1	1
GNAZ	-0.052	0.2	-9999	-0.8	17	17
RBBP4	0	0	-9999	-10000	0	0
CSNK1G1	0	0	-9999	-10000	0	0
PIAS1	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GLI2/SPOP	0	0	-9999	-10000	0	0
STK36	0.004	0.005	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.064	0.14	-9999	-0.56	10	10
PTCH1	-0.005	0.094	-9999	-10000	0	0
MIM/GLI1	-0.026	0.094	-9999	-0.41	3	3
CREBBP	-0.02	0.057	-9999	-0.38	3	3
Su(fu)/SIN3/HDAC complex	0	0.009	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class III

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0	0	-9999	-10000	0	0
HDAC4	-0.003	0.049	-9999	-0.8	1	1
induction of apoptosis	0	0	-9999	-10000	0	0
regulation of S phase of mitotic cell cycle	0	0	-9999	-10000	0	0
CDKN1A	0	0	-9999	-10000	0	0
KAT2B	0	0	-9999	-10000	0	0
BAX	0	0	-9999	-10000	0	0
FOXO3	0	0.007	-9999	-10000	0	0
FOXO1	0	0	-9999	-10000	0	0
FOXO4	0	0	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
XRCC6	0	0	-9999	-10000	0	0
TAT	-0.001	0.02	-9999	-0.32	1	1
mol:Lysophosphatidic acid	0	0	-9999	-10000	0	0
MYOD1	-0.021	0.081	-9999	-10000	0	0
PPARGC1A	-0.16	0.32	-9999	-0.79	54	54
FHL2	-0.001	0.02	-9999	-0.32	1	1
response to nutrient levels	0	0	-9999	-10000	0	0
KU70/SIRT1	0	0	-9999	-10000	0	0
HIST2H4A	0	0	-9999	-10000	0	0
SIRT1/FOXO3a	0	0.005	-9999	-10000	0	0
SIRT1	0	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
SIRT1/MEF2D/HDAC4	-0.002	0.033	-9999	-0.53	1	1
SIRT1/Histone H1b	-0.003	0.012	-9999	-10000	0	0
apoptosis	0	0	-9999	-10000	0	0
SIRT1/PGC1A	-0.11	0.22	-9999	-0.53	53	53
p53/SIRT1	0	0	-9999	-10000	0	0
SIRT1/FOXO4	0	0	-9999	-10000	0	0
FOXO1/FHL2/SIRT1	-0.001	0.009	-9999	-10000	0	0
HIST1H1E	-0.005	0.017	-9999	-10000	0	0
SIRT1/p300	0	0	-9999	-10000	0	0
muscle cell differentiation	0.025	0.059	-9999	-10000	0	0
TP53	0	0	-9999	-10000	0	0
KU70/SIRT1/BAX	0	0	-9999	-10000	0	0
CREBBP	0	0	-9999	-10000	0	0
MEF2D	0	0	-9999	-10000	0	0
HIV-1 Tat/SIRT1	-0.001	0.013	-9999	-10000	0	0
ACSS2	0	0	-9999	-10000	0	0
SIRT1/PCAF/MYOD	-0.026	0.06	-9999	-10000	0	0

×

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

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	-0.001	0.02	-9999	-0.32	1	1
Caspase 8 (4 units)	-0.014	0.033	-9999	-10000	0	0
NEF	-0.015	0.033	-9999	-10000	0	0
NFKBIA	-0.001	0.012	-9999	-10000	0	0
BIRC3	-0.01	0.088	-9999	-0.8	3	3
CYCS	0.024	0.05	-9999	-10000	0	0
RIPK1	0	0	-9999	-10000	0	0
CD247	-0.042	0.12	-9999	-0.41	22	22
MAP2K7	0.027	0.041	-9999	-0.33	1	1
protein ubiquitination	0.054	0.03	-9999	-10000	0	0
CRADD	-0.003	0.049	-9999	-0.8	1	1
DAXX	0	0	-9999	-10000	0	0
FAS	0	0	-9999	-10000	0	0
BID	-0.016	0.037	-9999	-0.29	1	1
NF-kappa-B/RelA/I kappa B alpha	-0.004	0.037	-9999	-0.34	3	3
TRADD	0	0	-9999	-10000	0	0
MAP3K5	-0.003	0.049	-9999	-0.8	1	1
CFLAR	0	0	-9999	-10000	0	0
FADD	0	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.005	0.038	-9999	-0.34	3	3
MAPK8	0.031	0.05	-9999	-0.48	1	1
APAF1	0	0	-9999	-10000	0	0
TRAF1	-0.004	0.034	-9999	-0.32	3	3
TRAF2	0	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.018	0.042	-9999	-0.31	1	1
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.002	0.031	-9999	-0.36	1	1
CHUK	0.055	0.032	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.002	0.028	-9999	-0.45	1	1
TCRz/NEF	-0.044	0.11	-9999	-0.37	21	21
TNF	-0.011	0.059	-9999	-0.32	9	9
FASLG	-0.059	0.13	-9999	-0.43	21	21
NFKB1	-0.001	0.012	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.006	0.032	-9999	-10000	0	0
CASP6	-0.007	0.022	-9999	-10000	0	0
CASP7	0.051	0.082	-9999	-0.62	3	3
RELA	-0.001	0.012	-9999	-10000	0	0
CASP2	0	0	-9999	-10000	0	0
CASP3	0.051	0.082	-9999	-0.62	3	3
TNFRSF1A	0	0	-9999	-10000	0	0
TNFR1A/BAG4	-0.001	0.013	-9999	-10000	0	0
CASP8	0	0	-9999	-10000	0	0
CASP9	0	0	-9999	-10000	0	0
MAP3K14	0.051	0.034	-9999	-10000	0	0
APAF-1/Caspase 9	-0.01	0.056	-9999	-0.5	3	3
BCL2	0.036	0.048	-9999	-0.44	1	1

×

TCGA08_rtk_signaling

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
PDGFRA	-0.075	0.22	-10000	0	-0.69	28	28
HRAS	0	0	-10000	0	-10000	0	0
EGFR	-0.006	0.057	-10000	0	-0.48	3	3
AKT	0.026	0.024	-10000	0	-0.29	1	1
FOXO3	-0.001	0.02	-10000	0	-0.32	1	1
AKT1	0	0	-10000	0	-10000	0	0
FOXO1	0	0	-10000	0	-10000	0	0
AKT3	-0.003	0.049	-10000	0	-0.8	1	1
FOXO4	0	0	-10000	0	-10000	0	0
MET	-0.012	0.098	-10000	0	-0.8	4	4
PIK3CA	0	0	-10000	0	-10000	0	0
PIK3CB	0	0	-10000	0	-10000	0	0
NRAS	0	0	-10000	0	-10000	0	0
PIK3CG	-0.016	0.07	-10000	0	-0.32	13	13
PIK3R3	0	0	-10000	0	-10000	0	0
PIK3R2	0	0	-10000	0	-10000	0	0
NF1	-0.003	0.049	-10000	0	-0.8	1	1
RAS	-0.005	0.07	0.25	1	-0.19	5	6
ERBB2	-0.028	0.15	-10000	0	-0.8	9	9
proliferation/survival/translation	-0.02	0.02	-10000	0	-10000	0	0
PI3K	0.002	0.066	-10000	0	-0.22	2	2
PIK3R1	-0.004	0.053	-10000	0	-0.56	2	2
KRAS	0	0	-10000	0	-10000	0	0
FOXO	0.032	0.015	-10000	0	-10000	0	0
AKT2	0	0	-10000	0	-10000	0	0
PTEN	0	0	-10000	0	-10000	0	0

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	0	0	-9999	-10000	0	0
DAPP1	0.025	0.037	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT/BTK-ITK	0.029	0.078	-9999	-0.66	2	2
mol:DAG	0.038	0.046	-9999	-0.25	1	1
HRAS	0	0	-9999	-10000	0	0
RAP1A	0	0	-9999	-10000	0	0
ARF5/GDP	-0.001	0.011	-9999	-10000	0	0
PLCG2	0	0	-9999	-10000	0	0
PLCG1	0	0	-9999	-10000	0	0
ARF5	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
ARF1/GTP	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
YES1	0	0	-9999	-10000	0	0
RAP1A/GTP	0	0	-9999	-10000	0	0
ADAP1	-0.013	0.072	-9999	-0.42	8	8
ARAP3	0	0	-9999	-10000	0	0
INPPL1	0	0	-9999	-10000	0	0
PREX1	-0.001	0.02	-9999	-0.32	1	1
ARHGEF6	0	0	-9999	-10000	0	0
ARHGEF7	0	0	-9999	-10000	0	0
ARF1	0	0	-9999	-10000	0	0
NRAS	0	0	-9999	-10000	0	0
FYN	-0.001	0.02	-9999	-0.32	1	1
ARF6	0	0	-9999	-10000	0	0
FGR	0	0	-9999	-10000	0	0
mol:Ca2+	0.03	0.025	-9999	-10000	0	0
mol:IP4	0	0	-9999	-10000	0	0
TIAM1	-0.01	0.056	-9999	-0.32	8	8
ZAP70	-0.046	0.11	-9999	-0.32	37	37
mol:IP3	0.037	0.033	-9999	-10000	0	0
LYN	0	0	-9999	-10000	0	0
ARF1/GDP	-0.001	0.011	-9999	-10000	0	0
RhoA/GDP	0	0.003	-9999	-10000	0	0
PDK1/Src/Hsp90	0	0	-9999	-10000	0	0
BLNK	-0.006	0.07	-9999	-0.8	2	2
actin cytoskeleton reorganization	0.052	0.018	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
PLEKHA2	0.023	0.023	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
PTEN	0	0	-9999	-10000	0	0
HSP90AA1	0	0	-9999	-10000	0	0
ARF6/GTP	0	0	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.018	0.063	-9999	-0.58	2	2
BLK	-0.035	0.1	-9999	-0.32	28	28
PDPK1	0	0	-9999	-10000	0	0
CYTH1	0	0	-9999	-10000	0	0
HCK	-0.015	0.068	-9999	-0.32	12	12
CYTH3	0	0	-9999	-10000	0	0
CYTH2	0	0	-9999	-10000	0	0
KRAS	0	0	-9999	-10000	0	0
GO:0030676	0	0	-9999	-10000	0	0
FOXO3	0	0.006	-9999	-10000	0	0
SGK1	0	0	-9999	-10000	0	0
INPP5D	-0.005	0.04	-9999	-0.32	4	4
mol:GDP	0.03	0.016	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
SYK	-0.007	0.073	-9999	-0.64	3	3
ARF6/GDP	0	0.003	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
ARAP3/RAP1A/GTP	0	0	-9999	-10000	0	0
VAV1	-0.025	0.095	-9999	-0.35	19	19
mol:PI-3-4-P2	0.015	0.028	-9999	-10000	0	0
RAS family/GTP/PI3K Class I	0	0	-9999	-10000	0	0
PLEKHA1	0.023	0.023	-9999	-10000	0	0
Rac1/GDP	-0.001	0.011	-9999	-10000	0	0
LAT	-0.012	0.062	-9999	-0.32	10	10
Rac1/GTP	-0.003	0.016	-9999	-10000	0	0
ITK	-0.012	0.034	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.043	0.059	-9999	-0.35	1	1
LCK	-0.039	0.11	-9999	-0.34	30	30
BTK	-0.001	0.012	-9999	-10000	0	0

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.022	0.038	-9999	-10000	0	0
PDGFB-D/PDGFRB/SLAP	-0.007	0.039	-9999	-10000	0	0
PDGFB-D/PDGFRB/APS/CBL	-0.001	0.014	-9999	-10000	0	0
AKT1	-0.007	0.051	-9999	-0.45	1	1
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	-0.024	0.041	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
FGR	0.002	0.009	-9999	-10000	0	0
mol:Ca2+	0.023	0.016	-9999	-10000	0	0
MYC	0.036	0.06	-9999	-0.87	1	1
SHC1	0	0	-9999	-10000	0	0
HRAS/GDP	0	0.007	-9999	-10000	0	0
LRP1/PDGFRB/PDGFB	-0.01	0.041	-9999	-0.33	1	1
GRB10	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
GO:0007205	0.023	0.016	-9999	-10000	0	0
PTEN	0	0	-9999	-10000	0	0
GRB2	0	0	-9999	-10000	0	0
GRB7	-0.14	0.3	-9999	-0.79	45	45
PDGFB-D/PDGFRB/SHP2	-0.001	0.013	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB10	-0.001	0.013	-9999	-10000	0	0
cell cycle arrest	-0.007	0.038	-9999	-10000	0	0
HRAS	0	0	-9999	-10000	0	0
HIF1A	0.05	0.053	-9999	-0.4	1	1
GAB1	0.02	0.028	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.022	0.031	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.001	0.01	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	-0.001	0.013	-9999	-10000	0	0
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.006	0.039	-9999	-10000	0	0
positive regulation of MAPKKK cascade	-0.001	0.013	-9999	-10000	0	0
PIK3R1	-0.004	0.053	-9999	-0.56	2	2
mol:IP3	0.023	0.016	-9999	-10000	0	0
E5	0	0.001	-9999	-10000	0	0
CSK	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.11	0.23	-9999	-0.62	44	44
SHB	0	0	-9999	-10000	0	0
BLK	0.001	0.008	-9999	-10000	0	0
PTPN2	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	-0.001	0.013	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
VAV2	0.026	0.03	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	-0.001	0.013	-9999	-10000	0	0
LCK	-0.002	0.039	-9999	-0.61	1	1
PDGFRB	-0.001	0.02	-9999	-0.32	1	1
ACP1	0	0	-9999	-10000	0	0
HCK	0.001	0.008	-9999	-10000	0	0
ABL1	0.022	0.021	-9999	-10000	0	0
PDGFB-D/PDGFRB/CBL	0.021	0.024	-9999	-10000	0	0
PTPN1	0	0	-9999	-10000	0	0
SNX15	0	0	-9999	-10000	0	0
STAT3	0	0	-9999	-10000	0	0
STAT1	-0.001	0.02	-9999	-0.32	1	1
cell proliferation	0.036	0.053	-9999	-0.75	1	1
SLA	-0.01	0.056	-9999	-0.32	8	8
actin cytoskeleton reorganization	0	0.006	-9999	-10000	0	0
SRC	0.001	0.008	-9999	-10000	0	0
PI3K	-0.008	0.056	-9999	-0.51	1	1
PDGFB-D/PDGFRB/GRB7/SHC	-0.091	0.2	-9999	-0.53	44	44
SH2B2	-0.001	0.02	-9999	-0.32	1	1
PLCgamma1/SPHK1	-0.025	0.042	-9999	-10000	0	0
LYN	0.001	0.008	-9999	-10000	0	0
LRP1	-0.017	0.073	-9999	-0.32	14	14
SOS1	0	0	-9999	-10000	0	0
STAT5B	0	0	-9999	-10000	0	0
STAT5A	0	0	-9999	-10000	0	0
NCK1-2/p130 Cas	0	0.007	-9999	-10000	0	0
SPHK1	-0.083	0.14	-9999	-0.32	67	67
EDG1	0	0.001	-9999	-10000	0	0
mol:DAG	0.023	0.016	-9999	-10000	0	0
PLCG1	0.024	0.016	-9999	-10000	0	0
NHERF/PDGFRB	-0.009	0.066	-9999	-0.53	4	4
YES1	0.002	0.009	-9999	-10000	0	0
cell migration	-0.009	0.066	-9999	-0.52	4	4
SHC/Grb2/SOS1	0	0.007	-9999	-10000	0	0
SLC9A3R2	0	0	-9999	-10000	0	0
SLC9A3R1	-0.012	0.098	-9999	-0.8	4	4
NHERF1-2/PDGFRB/PTEN	-0.008	0.06	-9999	-0.48	4	4
FYN	0.001	0.008	-9999	-10000	0	0
DOK1	0	0.009	-9999	-10000	0	0
HRAS/GTP	0	0	-9999	-10000	0	0
PDGFB	0	0	-9999	-10000	0	0
RAC1	0.033	0.04	-9999	-0.46	1	1
PRKCD	0	0.009	-9999	-10000	0	0
FER	0	0.009	-9999	-10000	0	0
MAPKKK cascade	0	0.007	-9999	-10000	0	0
RASA1	0	0.009	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
NCK2	0	0	-9999	-10000	0	0
p62DOK/Csk	0	0.008	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHB	-0.001	0.013	-9999	-10000	0	0
chemotaxis	0.022	0.02	-9999	-10000	0	0
STAT1-3-5/STAT1-3-5	-0.001	0.009	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	-0.001	0.013	-9999	-0.22	1	1
PTPRJ	0	0	-9999	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0	0	-9999	-10000	0	0
ITGB7	-0.002	0.028	-9999	-0.32	2	2
ITGA4	-0.007	0.048	-9999	-0.32	6	6
alpha4/beta7 Integrin	-0.006	0.036	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.005	0.031	-9999	-10000	0	0

×

HIF-2-alpha transcription factor network

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
MMP14	-0.026	0.057	-10000	0	-10000	0	0
oxygen homeostasis	0.009	0.011	-10000	0	-10000	0	0
TCEB2	0	0	-10000	0	-10000	0	0
TCEB1	0	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.034	0.085	-10000	0	-0.4	1	1
EPO	0.1	0.15	-10000	0	-10000	0	0
FIH (dimer)	0.016	0.012	-10000	0	-10000	0	0
APEX1	0.003	0.006	-10000	0	-10000	0	0
SERPINE1	0.081	0.19	-10000	0	-0.6	2	2
FLT1	0.002	0.013	-10000	0	-10000	0	0
ADORA2A	0.096	0.16	-10000	0	-0.56	1	1
germ cell development	0.094	0.17	-10000	0	-0.94	1	1
SLC11A2	0.096	0.17	-10000	0	-0.57	1	1
BHLHE40	0.096	0.17	-10000	0	-0.57	1	1
HIF1AN	0.016	0.012	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.025	0.095	-10000	0	-0.41	3	3
ETS1	0.021	0	-10000	0	-10000	0	0
CITED2	0	0.015	-10000	0	-10000	0	0
KDR	0.002	0.013	-10000	0	-10000	0	0
PGK1	0.096	0.17	-10000	0	-0.57	1	1
SIRT1	0	0	-10000	0	-10000	0	0
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	-0.02	0.12	-10000	0	-0.67	1	1
EPAS1	0.035	0.14	-10000	0	-0.36	16	16
SP1	0.012	0.005	-10000	0	-10000	0	0
ABCG2	0.095	0.17	-10000	0	-0.57	1	1
EFNA1	0.096	0.17	-10000	0	-0.57	1	1
FXN	0.096	0.16	-10000	0	-0.56	1	1
POU5F1	0.094	0.17	-10000	0	-1	1	1
neuron apoptosis	0.02	0.12	0.65	1	-10000	0	1
EP300	0	0	-10000	0	-10000	0	0
EGLN3	-0.084	0.27	-10000	0	-0.79	32	32
EGLN2	0.015	0.012	-10000	0	-10000	0	0
EGLN1	0.016	0.012	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0	0	-10000	0	-10000	0	0
VHL	0	0	-10000	0	-10000	0	0
ARNT	0.003	0.006	-10000	0	-10000	0	0
SLC2A1	0.089	0.17	-10000	0	-0.56	1	1
TWIST1	0.064	0.2	-10000	0	-0.64	2	2
ELK1	0.013	0.021	-10000	0	-0.32	1	1
HIF2A/ARNT/Cbp/p300	-0.024	0.093	-10000	0	-0.48	1	1
VEGFA	0.096	0.17	-10000	0	-0.57	1	1
CREBBP	0	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.003	0.015	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.001	0.007	-9999	-10000	0	0
SUMO1	0	0	-9999	-10000	0	0
ZFPM1	-0.001	0.02	-9999	-0.32	1	1
NPC/RanGAP1/SUMO1/Ubc9	0	0	-9999	-10000	0	0
FKBP3	0	0	-9999	-10000	0	0
Histones	-0.001	0.006	-9999	-10000	0	0
YY1/LSF	0	0	-9999	-10000	0	0
SMG5	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	-0.002	0.013	-9999	-10000	0	0
I kappa B alpha/HDAC1	-0.002	0.009	-9999	-10000	0	0
SAP18	0	0	-9999	-10000	0	0
RELA	-0.002	0.009	-9999	-10000	0	0
HDAC1/Smad7	0	0	-9999	-10000	0	0
RANGAP1	0	0	-9999	-10000	0	0
HDAC3/TR2	-0.002	0.009	-9999	-10000	0	0
NuRD/MBD3 Complex	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.001	0.007	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.009	0.075	-9999	-0.56	4	4
GATA1	-0.14	0.3	-9999	-0.79	47	47
Mad/Max	0	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	-0.04	0.085	-9999	-10000	0	0
RBBP7	0	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
RBBP4	0	0	-9999	-10000	0	0
MAX	0	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
NFKBIA	-0.002	0.012	-9999	-10000	0	0
KAT2B	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0	0	-9999	-10000	0	0
SIN3 complex	0	0	-9999	-10000	0	0
SMURF1	0	0	-9999	-10000	0	0
CHD3	0	0	-9999	-10000	0	0
SAP30	0	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0	0	-9999	-10000	0	0
YY1/HDAC3	-0.001	0.007	-9999	-10000	0	0
YY1/HDAC2	0	0	-9999	-10000	0	0
YY1/HDAC1	0	0	-9999	-10000	0	0
NuRD/MBD2 Complex (MeCP1)	0	0	-9999	-10000	0	0
PPARG	-0.003	0.012	-9999	-10000	0	0
HDAC8/hEST1B	0	0	-9999	-10000	0	0
UBE2I	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
TNFRSF1A	0	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	-0.002	0.009	-9999	-10000	0	0
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
CREBBP	0	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0	0	-9999	-10000	0	0
HDAC1	0	0	-9999	-10000	0	0
HDAC3	-0.002	0.012	-9999	-10000	0	0
HDAC2	0	0	-9999	-10000	0	0
YY1	0	0	-9999	-10000	0	0
HDAC8	0	0	-9999	-10000	0	0
SMAD7	0	0	-9999	-10000	0	0
NCOR2	0	0	-9999	-10000	0	0
MXD1	0	0	-9999	-10000	0	0
STAT3	0	0	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0	0	-9999	-10000	0	0
YY1/LSF/HDAC1	0	0	-9999	-10000	0	0
YY1/SAP30/HDAC1	0	0	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.002	0.012	-9999	-10000	0	0
histone deacetylation	0	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	-0.001	0.007	-9999	-10000	0	0
nuclear export	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GATAD2B	0	0	-9999	-10000	0	0
GATAD2A	0	0	-9999	-10000	0	0
GATA2/HDAC3	-0.007	0.044	-9999	-0.48	2	2
GATA1/HDAC1	-0.11	0.23	-9999	-0.61	46	46
GATA1/HDAC3	-0.087	0.18	-9999	-0.48	46	46
CHD4	0	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.007	0.038	-9999	-10000	0	0
SIN3/HDAC complex/Mad/Max	0	0	-9999	-10000	0	0
NuRD Complex	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.001	0.006	-9999	-10000	0	0
SIN3B	0	0	-9999	-10000	0	0
MTA2	0	0	-9999	-10000	0	0
SIN3A	0	0	-9999	-10000	0	0
XPO1	0	0	-9999	-10000	0	0
SUMO1/HDAC1	0	0	-9999	-10000	0	0
HDAC complex	0	0	-9999	-10000	0	0
GATA1/Fog1	-0.11	0.23	-9999	-0.61	46	46
FKBP25/HDAC1/HDAC2	0	0	-9999	-10000	0	0
TNF	-0.011	0.059	-9999	-0.32	9	9
negative regulation of cell growth	0	0	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.002	0.009	-9999	-10000	0	0
SIN3/HDAC complex/NCoR1	0	0	-9999	-10000	0	0
TFCP2	0	0	-9999	-10000	0	0
NR2C1	0	0	-9999	-10000	0	0
MBD3	0	0	-9999	-10000	0	0
MBD2	0	0	-9999	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0	0	-9999	-10000	0	0
Rac1/GDP	0.001	0.004	-9999	-10000	0	0
DOCK1	0	0	-9999	-10000	0	0
ITGA4	-0.007	0.048	-9999	-0.32	6	6
RAC1	0	0	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.006	0.036	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.004	0.025	-9999	-10000	0	0
alpha4/beta7 Integrin/Paxillin	-0.004	0.024	-9999	-10000	0	0
lamellipodium assembly	-0.001	0.03	-9999	-0.47	1	1
PIK3CA	0	0	-9999	-10000	0	0
PI3K	-0.003	0.04	-9999	-0.61	1	1
ARF6	0	0	-9999	-10000	0	0
TLN1	0	0	-9999	-10000	0	0
PXN	0.019	0	-9999	-10000	0	0
PIK3R1	-0.004	0.053	-9999	-0.56	2	2
ARF6/GTP	-0.002	0.016	-9999	-10000	0	0
cell adhesion	-0.003	0.018	-9999	-10000	0	0
CRKL/CBL	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	-0.003	0.021	-9999	-10000	0	0
ITGB1	0	0	-9999	-10000	0	0
ITGB7	-0.002	0.028	-9999	-0.32	2	2
ARF6/GDP	0.001	0.004	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.039	0.12	-9999	-0.45	21	21
p130Cas/Crk/Dock1	0	0	-9999	-10000	0	0
VCAM1	-0.065	0.22	-9999	-0.8	21	21
alpha4/beta1 Integrin/Paxillin/Talin	-0.003	0.018	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.003	0.018	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
mol:GDP	0.003	0.018	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GIT1	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.003	0.018	-9999	-10000	0	0
Rac1/GTP	-0.001	0.033	-9999	-0.52	1	1

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0	0	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.005	0.043	-9999	-0.66	1	1
NFKBIA	0.013	0.055	-9999	-0.51	2	2
MAPK14	0	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0	0	-9999	-10000	0	0
ARRB2	0	0	-9999	-10000	0	0
REL	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0	0	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
NF kappa B1 p50 dimer	0	0	-9999	-10000	0	0
PIK3R1	-0.004	0.053	-9999	-0.56	2	2
NFKB1	0.019	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	-0.006	0.038	-9999	-0.4	2	2
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	-0.004	0.042	-9999	-0.64	1	1
SRC	0	0	-9999	-10000	0	0
PI3K	-0.003	0.04	-9999	-0.61	1	1
NF kappa B1 p50/RelA	-0.006	0.038	-9999	-0.41	2	2
IKBKB	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
SYK	-0.007	0.073	-9999	-0.64	3	3
I kappa B alpha/PIK3R1	-0.009	0.055	-9999	-0.58	2	2
cell death	-0.004	0.039	-9999	-0.6	1	1
NF kappa B1 p105/c-Rel	0	0	-9999	-10000	0	0
LCK	-0.039	0.11	-9999	-0.34	30	30
BCL3	0	0	-9999	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.001	0.023	-9999	-0.37	1	1
MDM2/SUMO1	-0.024	0.05	-9999	-10000	0	0
HDAC4	-0.003	0.049	-9999	-0.8	1	1
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
SUMO1	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0	0	-9999	-10000	0	0
SUMO1/HDAC4	-0.002	0.027	-9999	-0.44	1	1
SUMO1/HDAC1	0	0	-9999	-10000	0	0
RANGAP1	0	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	-0.027	0.055	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0	0	-9999	-10000	0	0
Ran/GTP	0	0	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	-0.062	0.13	-9999	-0.32	50	50
UBE2I	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
PIAS2	0	0	-9999	-10000	0	0
PIAS1	0	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	-0.002	0.029	-9999	-0.46	1	1
TRAF2/ASK1	-0.002	0.033	-9999	-0.53	1	1
ATM	0	0	-9999	-10000	0	0
MAP2K3	0.029	0.021	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.027	0.054	-9999	-0.42	1	1
hyperosmotic response	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
GADD45G	-0.025	0.11	-9999	-0.41	16	16
TXN	0	0	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
GADD45A	-0.003	0.049	-9999	-0.8	1	1
GADD45B	0	0	-9999	-10000	0	0
MAP3K1	0	0	-9999	-10000	0	0
MAP3K6	0	0	-9999	-10000	0	0
MAP3K7	0	0	-9999	-10000	0	0
MAP3K4	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
ASK1/ASK2	-0.002	0.038	-9999	-0.61	1	1
TAK1/TAB family	0	0.004	-9999	-10000	0	0
RAC1/OSM/MEKK3	0	0	-9999	-10000	0	0
TRAF2	0	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.001	0.011	-9999	-10000	0	0
TRAF6	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
CAMK2B	-0.03	0.1	-9999	-0.34	23	23
CCM2	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.017	0.058	-9999	-0.53	1	1
MAPK11	-0.001	0.02	-9999	-0.32	1	1
response to DNA damage stimulus	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.016	0.058	-9999	-0.48	2	2
OSM/MEKK3	0	0	-9999	-10000	0	0
TAOK1	-0.003	0.015	-9999	-10000	0	0
TAOK2	0	0	-9999	-10000	0	0
TAOK3	0	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
MAP3K5	-0.003	0.049	-9999	-0.8	1	1
MAP3K10	0	0	-9999	-10000	0	0
MAP3K3	0	0	-9999	-10000	0	0
TRX/ASK1	-0.002	0.033	-9999	-0.52	1	1
GADD45/MTK1/MTK1	-0.014	0.066	-9999	-0.49	4	4

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0	0	-9999	-10000	0	0
SMAD2	0.013	0.006	-9999	-10000	0	0
SMAD3	0.031	0.017	-9999	-10000	0	0
SMAD3/SMAD4	0	0.001	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	0	0	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	0	0	-9999	-10000	0	0
PPM1A	0	0	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
SMAD2/SMAD4	0	0	-9999	-10000	0	0
MAP3K1	0	0	-9999	-10000	0	0
TRAP-1/SMAD4	-0.005	0.053	-9999	-0.61	2	2
MAPK3	0	0	-9999	-10000	0	0
MAPK1	0	0	-9999	-10000	0	0
NUP214	0	0	-9999	-10000	0	0
CTDSP1	0	0	-9999	-10000	0	0
CTDSP2	-0.012	0.062	-9999	-0.32	10	10
CTDSPL	0	0	-9999	-10000	0	0
KPNB1	0	0	-9999	-10000	0	0
TGFBRAP1	-0.006	0.07	-9999	-0.8	2	2
UBE2I	0	0	-9999	-10000	0	0
NUP153	0	0	-9999	-10000	0	0
KPNA2	0	0	-9999	-10000	0	0
PIAS4	0	0	-9999	-10000	0	0

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.066	0.022	-9999	-10000	0	0
ERC1	0	0	-9999	-10000	0	0
RIP2/NOD2	-0.011	0.046	-9999	-10000	0	0
NFKBIA	0.041	0	-9999	-10000	0	0
BIRC2	-0.001	0.02	-9999	-0.32	1	1
IKBKB	0	0	-9999	-10000	0	0
RIPK2	0	0	-9999	-10000	0	0
IKBKG	-0.001	0.005	-9999	-10000	0	0
IKK complex/A20	-0.004	0.021	-9999	-10000	0	0
NEMO/A20/RIP2	0	0	-9999	-10000	0	0
XPO1	0	0	-9999	-10000	0	0
NEMO/ATM	-0.001	0.003	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
Exportin 1/RanGTP	0	0	-9999	-10000	0	0
IKK complex/ELKS	0	0	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0	0	-9999	-10000	0	0
NOD2	-0.016	0.07	-9999	-0.32	13	13
NFKB1	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
MALT1	0	0	-9999	-10000	0	0
cIAP1/UbcH5C	-0.001	0.013	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
TNF/TNFR1A	-0.007	0.038	-9999	-10000	0	0
TRAF6	0	0	-9999	-10000	0	0
PRKCA	-0.006	0.07	-9999	-0.8	2	2
CHUK	0	0	-9999	-10000	0	0
UBE2D3	0	0	-9999	-10000	0	0
TNF	-0.011	0.059	-9999	-0.32	9	9
NF kappa B1 p50/RelA	0	0	-9999	-10000	0	0
BCL10	0	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.04	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
TNFRSF1A	0	0	-9999	-10000	0	0
IKK complex	0	0.001	-9999	-10000	0	0
CYLD	0	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.003	0.036	-9999	-0.43	1	1

×

Circadian rhythm 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	-0.001	0.008	-9999	-10000	0	0
CLOCK	-0.001	0.02	-9999	-0.32	1	1
TIMELESS/CRY2	-0.001	0.01	-9999	-10000	0	0
DEC1/BMAL1	-0.007	0.038	-9999	-10000	0	0
ATR	0	0	-9999	-10000	0	0
NR1D1	0.035	0.012	-9999	-10000	0	0
ARNTL	0	0	-9999	-10000	0	0
TIMELESS	0.034	0.015	-9999	-10000	0	0
NPAS2	-0.006	0.07	-9999	-0.79	2	2
CRY2	0	0	-9999	-10000	0	0
mol:CO	-0.011	0.003	-9999	-10000	0	0
CHEK1	0	0	-9999	-10000	0	0
mol:HEME	0.011	0.003	-9999	-10000	0	0
PER1	0	0	-9999	-10000	0	0
BMAL/CLOCK/NPAS2	-0.005	0.046	-9999	-0.52	2	2
BMAL1/CLOCK	0.014	0.026	-9999	-10000	0	0
S phase of mitotic cell cycle	-0.001	0.008	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	-0.001	0.008	-9999	-10000	0	0
mol:NADPH	0.011	0.003	-9999	-10000	0	0
PER1/TIMELESS	-0.001	0.01	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	-0.011	0.059	-9999	-0.32	9	9

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.008	0.067	-9999	-10000	0	0
regulation of axonogenesis	0.003	0.007	-9999	-10000	0	0
myoblast fusion	0.012	0.03	-9999	-10000	0	0
mol:GTP	-0.009	0.022	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.01	0.028	-9999	-10000	0	0
ARF1/GTP	-0.005	0.013	-9999	-10000	0	0
mol:GM1	0.001	0.019	-9999	-10000	0	0
mol:Choline	0.018	0.016	-9999	-10000	0	0
lamellipodium assembly	-0.01	0.031	-9999	-10000	0	0
MAPK3	0.008	0.036	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.01	0.028	-9999	-10000	0	0
ARF1	0	0	-9999	-10000	0	0
ARF6/GDP	-0.012	0.03	-9999	-10000	0	0
ARF1/GDP	-0.01	0.024	-9999	-10000	0	0
ARF6	-0.003	0.009	-9999	-10000	0	0
RAB11A	0	0	-9999	-10000	0	0
TIAM1	-0.01	0.055	-9999	-0.32	8	8
fibronectin binding	0	0	-9999	-10000	0	0
MAPK1	0.008	0.036	-9999	-10000	0	0
actin filament bundle formation	0.01	0.024	-9999	-10000	0	0
KALRN	-0.01	0.028	-9999	-10000	0	0
RAB11FIP3/RAB11A	0	0	-9999	-10000	0	0
RhoA/GDP	-0.01	0.024	-9999	-10000	0	0
NME1	0	0	-9999	-10000	0	0
Rac1/GDP	-0.01	0.024	-9999	-10000	0	0
substrate adhesion-dependent cell spreading	-0.009	0.022	-9999	-10000	0	0
cortical actin cytoskeleton organization	-0.01	0.031	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
liver development	-0.009	0.022	-9999	-10000	0	0
ARF6/GTP	-0.009	0.022	-9999	-10000	0	0
RhoA/GTP	-0.005	0.013	-9999	-10000	0	0
mol:GDP	-0.011	0.032	-9999	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	-0.003	0.007	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PLD1	-0.005	0.013	-9999	-10000	0	0
RAB11FIP3	0	0	-9999	-10000	0	0
tube morphogenesis	-0.01	0.031	-9999	-10000	0	0
ruffle organization	-0.003	0.007	-9999	-10000	0	0
regulation of epithelial cell migration	-0.009	0.022	-9999	-10000	0	0
PLD2	-0.005	0.013	-9999	-10000	0	0
PIP5K1A	-0.003	0.007	-9999	-10000	0	0
mol:Phosphatidic acid	0.018	0.016	-9999	-10000	0	0
Rac1/GTP	-0.01	0.031	-9999	-10000	0	0

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.067	0.011	-9999	-10000	0	0
CRKL	-0.002	0.012	-9999	-10000	0	0
mol:DAG	-0.001	0.006	-9999	-10000	0	0
HRAS	-0.001	0.007	-9999	-10000	0	0
MAPK8	-0.003	0.033	-9999	-0.49	1	1
RAP1A	-0.002	0.012	-9999	-10000	0	0
GAB1	-0.002	0.012	-9999	-10000	0	0
MAPK14	-0.001	0.013	-9999	-10000	0	0
EPO	-0.003	0.034	-9999	-0.31	3	3
PLCG1	-0.001	0.006	-9999	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0	0	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.002	0.016	-9999	-10000	0	0
GAB1/SHC/GRB2/SOS1	-0.001	0.008	-9999	-10000	0	0
EPO/EPOR (dimer)	-0.002	0.021	-9999	-10000	0	0
IRS2	-0.002	0.012	-9999	-10000	0	0
STAT1	0.052	0.015	-9999	-10000	0	0
STAT5B	-0.001	0.006	-9999	-10000	0	0
cell proliferation	0.035	0.034	-9999	-0.45	1	1
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.004	0.027	-9999	-10000	0	0
TEC	-0.007	0.046	-9999	-0.42	3	3
SOCS3	0	0	-9999	-10000	0	0
STAT1 (dimer)	0.052	0.015	-9999	-10000	0	0
JAK2	-0.001	0.019	-9999	-0.31	1	1
PIK3R1	-0.004	0.053	-9999	-0.56	2	2
EPO/EPOR (dimer)/JAK2	0.039	0.019	-9999	-10000	0	0
EPO/EPOR	-0.002	0.021	-9999	-10000	0	0
LYN	0	0	-9999	-10000	0	0
TEC/VAV2	-0.006	0.044	-9999	-0.4	3	3
elevation of cytosolic calcium ion concentration	0	0	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
EPO/EPOR (dimer)/LYN	-0.002	0.016	-9999	-10000	0	0
mol:IP3	-0.001	0.006	-9999	-10000	0	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.005	0.03	-9999	-0.38	1	1
SH2B3	0	0	-9999	-10000	0	0
NFKB1	-0.001	0.013	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2/SOCS3	-0.001	0.007	-9999	-10000	0	0
PTPN6	-0.002	0.013	-9999	-10000	0	0
TEC/VAV2/GRB2	-0.006	0.042	-9999	-10000	0	0
EPOR	0	0	-9999	-10000	0	0
INPP5D	-0.005	0.04	-9999	-0.32	4	4
mol:GDP	-0.001	0.008	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
PLCG2	0	0	-9999	-10000	0	0
CRKL/CBL/C3G	-0.001	0.009	-9999	-10000	0	0
VAV2	-0.002	0.012	-9999	-10000	0	0
CBL	-0.002	0.012	-9999	-10000	0	0
SHC/Grb2/SOS1	-0.001	0.009	-9999	-10000	0	0
STAT5A	-0.001	0.006	-9999	-10000	0	0
GRB2	0	0	-9999	-10000	0	0
STAT5 (dimer)	0	0.007	-9999	-10000	0	0
LYN/PLCgamma2	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
BTK	-0.003	0.02	-9999	-10000	0	0
BCL2	0.067	0.011	-9999	-10000	0	0

×

mTOR 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
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0	0	-10000	0	-10000	0	0
mol:PIP3	-0.002	0.028	-10000	0	-0.43	1	1
FRAP1	0.012	0.01	-10000	0	-10000	0	0
AKT1	-0.002	0.026	-10000	0	-0.4	1	1
INSR	0	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0	0	-10000	0	-10000	0	0
mol:GTP	-0.002	0.021	-10000	0	-0.33	1	1
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.001	0.008	-10000	0	-10000	0	0
TSC2	0	0	-10000	0	-10000	0	0
RHEB/GDP	-0.001	0.019	-10000	0	-0.3	1	1
TSC1	0	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0	0.002	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.001	0.009	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0	0	-10000	0	-10000	0	0
RPS6KB1	0.022	0.018	-10000	0	-0.26	1	1
MAP3K5	0.007	0.028	-10000	0	-0.45	1	1
PIK3R1	-0.004	0.053	-10000	0	-0.56	2	2
apoptosis	0.007	0.028	-10000	0	-0.44	1	1
mol:LY294002	0	0	0.001	1	-10000	0	1
EIF4B	0.027	0.016	-10000	0	-0.22	1	1
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.001	0.013	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	0	0.005	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	-0.002	0.029	-10000	0	-0.45	1	1
mTOR/RHEB/GTP/Raptor/GBL	0.026	0.014	-10000	0	-0.19	1	1
FKBP1A	0	0	-10000	0	-10000	0	0
RHEB/GTP	-0.001	0.019	-10000	0	-0.3	1	1
mol:Amino Acids	0	0	0.001	1	-10000	0	1
FKBP12/Rapamycin	0	0	-10000	0	-10000	0	0
PDPK1	-0.002	0.026	-10000	0	-0.4	1	1
EIF4E	0	0	-10000	0	-10000	0	0
ASK1/PP5C	-0.003	0.039	-10000	0	-0.63	1	1
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0	0.001	-10000	0	-10000	0	0
TSC1/TSC2	-0.002	0.023	-10000	0	-0.36	1	1
tumor necrosis factor receptor activity	0	0	-10000	0	-0.001	1	1
RPS6	0	0	-10000	0	-10000	0	0
PPP5C	0	0	-10000	0	-10000	0	0
EIF4G1	0	0	-10000	0	-10000	0	0
IRS1	0.006	0.003	-10000	0	-10000	0	0
INS	0	0	-10000	0	-10000	0	0
PTEN	0	0.001	-10000	0	-10000	0	0
PDK2	-0.002	0.026	-10000	0	-0.4	1	1
EIF4EBP1	0.008	0	-10000	0	-10000	0	0
PIK3CA	0	0	-10000	0	-10000	0	0
PPP2R5D	0.018	0.01	-10000	0	-10000	0	0
peptide biosynthetic process	0	0	-10000	0	-10000	0	0
RHEB	0	0	-10000	0	-10000	0	0
EIF4A1	0	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	-10000	0	-0.003	1	1
EEF2	0	0	-10000	0	-10000	0	0
eIF4E/4E-BP1	0	0	-10000	0	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.036	0.044	-9999	-10000	0	0
BAG4	-0.001	0.02	-9999	-0.32	1	1
BAD	0.027	0.015	-9999	-10000	0	0
NFKBIA	0	0	-9999	-10000	0	0
BIRC3	-0.011	0.088	-9999	-0.68	4	4
BAX	0.027	0.015	-9999	-10000	0	0
EnzymeConsortium:3.1.4.12	0.012	0.011	-9999	-10000	0	0
IKBKB	0.042	0.042	-9999	-10000	0	0
MAP2K2	0.038	0.016	-9999	-10000	0	0
MAP2K1	0.038	0.016	-9999	-10000	0	0
SMPD1	0.017	0.011	-9999	-10000	0	0
GO:0005551	0	0	-9999	-10000	0	0
FADD/Caspase 8	0.043	0.042	-9999	-10000	0	0
MAP2K4	0.033	0.014	-9999	-10000	0	0
protein ubiquitination	0.044	0.042	-9999	-10000	0	0
EnzymeConsortium:2.7.1.37	0.043	0.017	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
RAF1	0.033	0.017	-9999	-10000	0	0
CRADD	-0.003	0.05	-9999	-0.8	1	1
mol:ceramide	0.021	0.015	-9999	-10000	0	0
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-9999	-10000	0	0
MADD	0	0	-9999	-10000	0	0
MAP3K1	0.027	0.015	-9999	-10000	0	0
TRADD	0	0	-9999	-10000	0	0
RELA/p50	0	0	-9999	-10000	0	0
MAPK3	0.04	0.016	-9999	-10000	0	0
MAPK1	0.04	0.016	-9999	-10000	0	0
p50/RELA/I-kappa-B-alpha	0	0	-9999	-10000	0	0
FADD	0.037	0.043	-9999	-10000	0	0
KSR1	0.027	0.017	-9999	-10000	0	0
MAPK8	0.037	0.029	-9999	-0.38	1	1
TRAF2	0	0	-9999	-10000	0	0
response to radiation	0	0	-9999	-10000	0	0
CHUK	0.042	0.042	-9999	-10000	0	0
TNF R/SODD	-0.001	0.013	-9999	-10000	0	0
TNF	-0.011	0.059	-9999	-0.32	9	9
CYCS	0.028	0.014	-9999	-10000	0	0
IKBKG	0.042	0.042	-9999	-10000	0	0
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.004	0.04	-9999	-0.34	3	3
RELA	0	0	-9999	-10000	0	0
RIPK1	0	0	-9999	-10000	0	0
AIFM1	0.028	0.014	-9999	-10000	0	0
TNF/TNF R/SODD	-0.006	0.031	-9999	-10000	0	0
TNFRSF1A	0	0	-9999	-10000	0	0
response to heat	0	0	-9999	-10000	0	0
CASP8	0	0.01	-9999	-10000	0	0
NSMAF	0.037	0.042	-9999	-10000	0	0
response to hydrogen peroxide	0	0	-9999	-10000	0	0
BCL2	0	0	-9999	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.012	0.084	-9999	-0.61	5	5
AKT1	0.073	0.03	-9999	-10000	0	0
PTK2B	-0.01	0.071	-9999	-0.82	1	1
VEGFR2 homodimer/Frs2	-0.014	0.051	-9999	-0.5	1	1
CAV1	-0.003	0.049	-9999	-0.8	1	1
CALM1	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.012	0.044	-9999	-0.45	1	1
endothelial cell proliferation	0.079	0.053	-9999	-0.5	1	1
mol:Ca2+	-0.002	0.025	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.002	0.026	-9999	-10000	0	0
RP11-342D11.1	-0.002	0.026	-9999	-0.41	1	1
CDH5	0	0	-9999	-10000	0	0
VEGFA homodimer	0	0	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
SHC2	-0.002	0.028	-9999	-0.32	2	2
HRAS/GDP	-0.001	0.021	-9999	-10000	0	0
SH2D2A	-0.034	0.098	-9999	-0.32	27	27
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.001	0.021	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.015	0.048	-9999	-0.45	1	1
VEGFR1 homodimer	0	0	-9999	-10000	0	0
SHC/GRB2/SOS1	-0.001	0.023	-9999	-10000	0	0
GRB10	-0.002	0.025	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
GRB2	0	0	-9999	-10000	0	0
PAK1	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.002	0.025	-9999	-10000	0	0
HRAS	0	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	-0.006	0.044	-9999	-0.52	1	1
HIF1A	0	0	-9999	-10000	0	0
FRS2	-0.025	0.086	-9999	-0.32	20	20
oxygen and reactive oxygen species metabolic process	-0.002	0.026	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
FLT4	-0.001	0.02	-9999	-0.32	1	1
Nck/Pak	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.002	0.029	-9999	-0.45	1	1
mol:GDP	-0.001	0.023	-9999	-10000	0	0
mol:NADP	0.065	0.022	-9999	-10000	0	0
eNOS/Hsp90	0.066	0.021	-9999	-10000	0	0
PIK3R1	-0.004	0.053	-9999	-0.56	2	2
mol:IP3	-0.002	0.026	-9999	-10000	0	0
HIF1A/ARNT	0	0	-9999	-10000	0	0
SHB	0	0	-9999	-10000	0	0
VEGFA	0	0	-9999	-10000	0	0
VEGFC	0	0	-9999	-10000	0	0
FAK1/Vinculin	-0.007	0.054	-9999	-0.69	1	1
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.01	0.076	-9999	-0.52	5	5
PTPN6	-0.001	0.02	-9999	-0.32	1	1
EPAS1	-0.003	0.048	-9999	-0.78	1	1
mol:L-citrulline	0.065	0.022	-9999	-10000	0	0
ITGAV	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.01	0.039	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer	-0.002	0.028	-9999	-0.45	1	1
VEGFR2/3 heterodimer	-0.003	0.033	-9999	-0.5	1	1
VEGFB	0	0	-9999	-10000	0	0
MAPK11	0.051	0.031	-9999	-10000	0	0
VEGFR2 homodimer	0.027	0.038	-9999	-0.58	1	1
FLT1	0	0	-9999	-10000	0	0
NEDD4	0	0	-9999	-10000	0	0
MAPK3	0.052	0.041	-9999	-0.52	1	1
MAPK1	0.052	0.041	-9999	-0.52	1	1
VEGFA145/NRP2	0	0	-9999	-10000	0	0
VEGFR1/2 heterodimer	-0.002	0.031	-9999	-0.5	1	1
KDR	0.027	0.038	-9999	-0.59	1	1
VEGFA165/NRP1/VEGFR2 homodimer	-0.002	0.025	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.054	0.041	-9999	-0.52	1	1
PI3K	-0.002	0.026	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.002	0.028	-9999	-0.45	1	1
FES	-0.002	0.026	-9999	-10000	0	0
GAB1	-0.002	0.024	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src	-0.002	0.028	-9999	-0.45	1	1
CTNNB1	0	0	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
ARNT	0	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.064	0.041	-9999	-0.59	1	1
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.002	0.028	-9999	-0.45	1	1
PI3K/GAB1	-0.002	0.03	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.009	0.036	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.002	0.029	-9999	-0.46	1	1
HSP90AA1	0	0	-9999	-10000	0	0
CDC42	-0.002	0.026	-9999	-10000	0	0
actin cytoskeleton reorganization	-0.015	0.047	-9999	-0.45	1	1
PTK2	0.052	0.066	-9999	-0.75	1	1
EDG1	-0.002	0.026	-9999	-0.41	1	1
mol:DAG	-0.002	0.026	-9999	-10000	0	0
CaM/Ca2+	-0.001	0.023	-9999	-10000	0	0
MAP2K3	0.051	0.049	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.002	0.026	-9999	-10000	0	0
PLCG1	-0.002	0.026	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.002	0.026	-9999	-10000	0	0
IQGAP1	0	0	-9999	-10000	0	0
YES1	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.002	0.028	-9999	-0.45	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.002	0.029	-9999	-0.45	1	1
cell migration	0.073	0.053	-9999	-0.56	1	1
mol:PI-3-4-5-P3	-0.002	0.025	-9999	-10000	0	0
FYN	-0.001	0.02	-9999	-0.32	1	1
VEGFB/NRP1	-0.001	0.024	-9999	-10000	0	0
mol:NO	0.065	0.022	-9999	-10000	0	0
PXN	0	0	-9999	-10000	0	0
HRAS/GTP	-0.001	0.021	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.002	0.026	-9999	-10000	0	0
VHL	0	0	-9999	-10000	0	0
ITGB3	-0.015	0.11	-9999	-0.8	5	5
NOS3	0.067	0.024	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.003	0.03	-9999	-0.45	1	1
RAC1	0	0	-9999	-10000	0	0
PRKCA	0.05	0.049	-9999	-10000	0	0
PRKCB	0.048	0.069	-9999	-0.82	1	1
VCL	0	0	-9999	-10000	0	0
VEGFA165/NRP1	-0.002	0.026	-9999	-0.41	1	1
VEGFR1/2 heterodimer/VEGFA homodimer	-0.002	0.028	-9999	-0.45	1	1
VEGFA165/NRP2	0	0	-9999	-10000	0	0
MAPKKK cascade	-0.001	0.021	-9999	-10000	0	0
NRP2	0	0	-9999	-10000	0	0
VEGFC homodimer	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
ROCK1	0	0	-9999	-10000	0	0
FAK1/Paxillin	-0.007	0.054	-9999	-0.69	1	1
MAP3K13	-0.005	0.046	-9999	-10000	0	0
PDPK1	-0.002	0.022	-9999	-10000	0	0

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP1	0	0	-9999	-10000	0	0
mol:DAG	-0.007	0.029	-9999	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	0	0	-9999	-10000	0	0
CaM/Ca2+	-0.006	0.026	-9999	-10000	0	0
HIF1A	0	0	-9999	-10000	0	0
GAB1	0	0	-9999	-10000	0	0
AKT1	-0.006	0.031	-9999	-10000	0	0
PLCG1	-0.007	0.029	-9999	-10000	0	0
NOS3	0.048	0.028	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
mol:NO	0.047	0.028	-9999	-10000	0	0
FLT1	0.024	0	-9999	-10000	0	0
PGF	-0.016	0.07	-9999	-0.32	13	13
VEGFR1 homodimer/NRP2/VEGFR121	0	0	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
eNOS/Hsp90	-0.003	0.013	-9999	-10000	0	0
endothelial cell proliferation	0.034	0.059	-9999	-0.45	1	1
mol:Ca2+	-0.007	0.029	-9999	-10000	0	0
MAPK3	0.035	0.051	-9999	-0.42	2	2
MAPK1	0.035	0.051	-9999	-0.42	2	2
PIK3R1	-0.004	0.053	-9999	-0.56	2	2
PLGF homodimer	-0.016	0.07	-9999	-0.32	13	13
PRKACA	0	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.003	0.049	-9999	-0.8	1	1
VEGFA homodimer	0	0	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.041	0.05	-9999	-10000	0	0
PI3K	-0.008	0.038	-9999	-0.44	1	1
PRKCA	0.029	0.054	-9999	-0.44	2	2
PRKCB	0.026	0.062	-9999	-0.44	3	3
VEGFR1 homodimer/PLGF homodimer	-0.008	0.035	-9999	-10000	0	0
VEGFA	0	0	-9999	-10000	0	0
VEGFB	0	0	-9999	-10000	0	0
mol:IP3	-0.007	0.029	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
NRP2	0	0	-9999	-10000	0	0
VEGFR1 homodimer	0.024	0	-9999	-10000	0	0
VEGFB homodimer	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.005	0.027	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.008	0.038	-9999	-0.44	1	1
mol:L-citrulline	0.047	0.028	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0	0	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	0	0	-9999	-10000	0	0
CD2AP	0	0	-9999	-10000	0	0
PI3K/GAB1	-0.007	0.035	-9999	-10000	0	0
PDPK1	-0.007	0.034	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/SHP2	0	0	-9999	-10000	0	0
mol:NADP	0.047	0.028	-9999	-10000	0	0
HSP90AA1	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP2	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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0	0.002	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.016	0	-9999	-10000	0	0
AP2	0	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0	-9999	-10000	0	0
CLTB	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0	0.004	-9999	-10000	0	0
CD4	-0.007	0.048	-9999	-0.32	6	6
CLTA	0	0	-9999	-10000	0	0
mol:GTP	0.001	0	-9999	-10000	0	0
ARFGAP1	0.009	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
ARF1/GTP	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0	0.002	-9999	-10000	0	0
mol:Choline	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0	0	-9999	-10000	0	0
DDEF1	0	0	-9999	-10000	0	0
ARF1/GDP	0	0	-9999	-10000	0	0
AP2M1	0	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0	0	-9999	-10000	0	0
Rac/GTP	0	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0	0	-9999	-10000	0	0
ARFIP2	0	0	-9999	-10000	0	0
COPA	-0.001	0.02	-9999	-0.32	1	1
RAC1	0	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0	0.002	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0	-9999	-10000	0	0
GGA3	0	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0	0	-9999	-10000	0	0
AP2A1	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0	0.002	-9999	-10000	0	0
ARF1/GDP/Membrin	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0	0	-9999	-10000	0	0
CYTH2	0	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0	0	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0	0	-9999	-10000	0	0
mol:Brefeldin A	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	-0.001	0.005	-9999	-10000	0	0
PLD2	0	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.009	0	-9999	-10000	0	0
PIP5K1A	0	0	-9999	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0	0	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	0.009	0	-9999	-10000	0	0
GOSR2	0	0	-9999	-10000	0	0
USO1	0	0	-9999	-10000	0	0
GBF1	0	0	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	-0.004	0.025	-9999	-10000	0	0

×

Alternative NF-kappaB pathway

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

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

Entity	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
IKK alpha homodimer	-9999	-9999
FBXW11	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	-9999	-9999
beta TrCP1/SCF ubiquitin ligase complex	-9999	-9999
CHUK	-9999	-9999
NF kappa B2 p100/RelB	-9999	-9999
NFKB1	-9999	-9999
MAP3K14	-9999	-9999
NF kappa B1 p50/RelB	-9999	-9999
RELB	-9999	-9999
NFKB2	-9999	-9999
NF kappa B2 p52/RelB	-9999	-9999
regulation of B cell activation	-9999	-9999

pid_entity	TCGA.Z4.AAPG	TCGA.Z4.AAPF	TCGA.Z4.A9VC	TCGA.Z4.A8JB
109_MAP3K5	0.045	0.045	0.045	0.045
47_PPARGC1A	0	0	0	0
105_BMP4	0	0	0	0
105_BMP6	0	0	0	0
105_BMP7	0	-0.32	0	0
105_BMP2	0	0	0	0
131_RELN/VLDLR	0	0	-0.48	0
30_TGFB1/TGF beta receptor Type II	0	0	0	0
84_STAT5B	-0.059	0.037	0.036	-0.057
84_STAT5A	-0.059	0.037	0.036	-0.057