PARADIGM pathway analysis of mRNASeq expression data - Thyroid Adenocarcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
Ephrin A reverse signaling	211
Signaling events mediated by Stem cell factor receptor (c-Kit)	129
TCGA08_retinoblastoma	117
Signaling events regulated by Ret tyrosine kinase	116
Reelin signaling pathway	108
Wnt signaling	91
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	91
Noncanonical Wnt signaling pathway	87
FOXA2 and FOXA3 transcription factor networks	86
PDGFR-alpha signaling pathway	82

Pathway.Name	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
Ephrin A reverse signaling	211	1481	7	-0.54	0	1000	-1000	-0.032	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	129	10104	78	-0.78	0.23	1000	-1000	-0.09	-1000
TCGA08_retinoblastoma	117	941	8	-0.13	0.073	1000	-1000	-0.018	-1000
Signaling events regulated by Ret tyrosine kinase	116	9567	82	-0.48	0.013	1000	-1000	-0.089	-1000
Reelin signaling pathway	108	6052	56	-0.63	0.034	1000	-1000	-0.079	-1000
Wnt signaling	91	637	7	-0.44	0.013	1000	-1000	-0.022	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	91	6219	68	-0.9	0.35	1000	-1000	-0.12	-1000
Noncanonical Wnt signaling pathway	87	2266	26	-0.44	0.013	1000	-1000	-0.079	-1000
FOXA2 and FOXA3 transcription factor networks	86	3987	46	-0.97	0.021	1000	-1000	-0.054	-1000
PDGFR-alpha signaling pathway	82	3614	44	-0.51	0.033	1000	-1000	-0.066	-1000
IL4-mediated signaling events	73	6673	91	-1.3	0.66	1000	-1000	-0.15	-1000
Nongenotropic Androgen signaling	70	3669	52	-0.35	0.16	1000	-1000	-0.059	-1000
Signaling events mediated by the Hedgehog family	68	3581	52	-0.41	0.21	1000	-1000	-0.081	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	66	3609	54	-0.63	0.028	1000	-1000	-0.089	-1000
Calcium signaling in the CD4+ TCR pathway	63	1956	31	-0.53	0.013	1000	-1000	-0.089	-1000
Nephrin/Neph1 signaling in the kidney podocyte	58	2004	34	-0.16	0.013	1000	-1000	-0.063	-1000
Endothelins	54	5187	96	-0.42	0.013	1000	-1000	-0.071	-1000
Glypican 1 network	52	2535	48	-0.4	0.029	1000	-1000	-0.053	-1000
Ephrin B reverse signaling	51	2487	48	-0.31	0.2	1000	-1000	-0.077	-1000
Glucocorticoid receptor regulatory network	49	5633	114	-0.58	0.38	1000	-1000	-0.067	-1000
Glypican 2 network	49	197	4	-0.087	-0.018	1000	-1000	-0.036	-1000
IL23-mediated signaling events	49	2999	60	-0.35	0.021	1000	-1000	-0.14	-1000
TCR signaling in naïve CD8+ T cells	47	4380	93	-0.2	0.088	1000	-1000	-0.076	-1000
IGF1 pathway	45	2572	57	-0.19	0.054	1000	-1000	-0.097	-1000
HIF-1-alpha transcription factor network	44	3365	76	-0.6	0.041	1000	-1000	-0.12	-1000
BMP receptor signaling	44	3572	81	-0.6	0.024	1000	-1000	-0.091	-1000
Arf6 signaling events	41	2561	62	-0.33	0.021	1000	-1000	-0.068	-1000
Coregulation of Androgen receptor activity	39	3016	76	-0.78	0.061	1000	-1000	-0.045	-1000
Syndecan-1-mediated signaling events	39	1350	34	-0.22	0.013	1000	-1000	-0.064	-1000
EPHB forward signaling	39	3349	85	-0.31	0.16	1000	-1000	-0.099	-1000
Signaling mediated by p38-alpha and p38-beta	35	1576	44	-0.24	0.013	1000	-1000	-0.05	-1000
Syndecan-4-mediated signaling events	33	2235	67	-0.26	0.013	1000	-1000	-0.096	-1000
IL12-mediated signaling events	32	2852	87	-0.41	0.02	1000	-1000	-0.11	-1000
Hedgehog signaling events mediated by Gli proteins	32	2115	65	-0.69	0.064	1000	-1000	-0.062	-1000
amb2 Integrin signaling	29	2436	82	-0.26	0.013	1000	-1000	-0.085	-1000
IL6-mediated signaling events	29	2239	75	-0.21	0.062	1000	-1000	-0.084	-1000
Ras signaling in the CD4+ TCR pathway	28	485	17	-0.097	0.012	1000	-1000	-0.045	-1000
EGFR-dependent Endothelin signaling events	27	572	21	-0.11	0.013	1000	-1000	-0.075	-1000
Osteopontin-mediated events	26	1000	38	-0.26	0.013	1000	-1000	-0.097	-1000
Thromboxane A2 receptor signaling	26	2760	105	-0.22	0.029	1000	-1000	-0.074	-1000
TCGA08_p53	24	169	7	-0.081	0.052	1000	-1000	-0.01	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	23	2018	85	-0.29	0.013	1000	-1000	-0.071	-1000
FAS signaling pathway (CD95)	23	1118	47	-0.28	0.027	1000	-1000	-0.048	-1000
Syndecan-2-mediated signaling events	22	1546	69	-0.22	0.037	1000	-1000	-0.062	-1000
BCR signaling pathway	22	2220	99	-0.2	0.022	1000	-1000	-0.091	-1000
Regulation of p38-alpha and p38-beta	21	1178	54	-0.49	0.013	1000	-1000	-0.056	-1000
Visual signal transduction: Rods	21	1100	52	-0.2	0.014	1000	-1000	-0.093	-1000
Regulation of Androgen receptor activity	21	1505	70	-0.48	0.034	1000	-1000	-0.061	-1000
JNK signaling in the CD4+ TCR pathway	20	341	17	-0.1	0.018	1000	-1000	-0.06	-1000
RXR and RAR heterodimerization with other nuclear receptor	20	1043	52	-0.28	0.054	1000	-1000	-0.061	-1000
Integrins in angiogenesis	20	1703	84	-0.23	0.032	1000	-1000	-0.1	-1000
LPA receptor mediated events	20	2075	102	-0.26	0.031	1000	-1000	-0.083	-1000
Plasma membrane estrogen receptor signaling	20	1747	86	-0.18	0.02	1000	-1000	-0.083	-1000
IL27-mediated signaling events	19	987	51	-0.19	0.058	1000	-1000	-0.074	-1000
Signaling events mediated by PRL	19	670	34	-0.12	0.013	1000	-1000	-0.048	-1000
ErbB2/ErbB3 signaling events	18	1219	65	-0.13	0.027	1000	-1000	-0.07	-1000
Signaling events mediated by PTP1B	18	1378	76	-0.26	0.021	1000	-1000	-0.079	-1000
Angiopoietin receptor Tie2-mediated signaling	18	1605	88	-0.33	0.03	1000	-1000	-0.11	-1000
p75(NTR)-mediated signaling	17	2214	125	-0.38	0.07	1000	-1000	-0.094	-1000
Fc-epsilon receptor I signaling in mast cells	17	1729	97	-0.21	0.03	1000	-1000	-0.076	-1000
VEGFR1 specific signals	17	979	56	-0.072	0.043	1000	-1000	-0.073	-1000
Regulation of nuclear SMAD2/3 signaling	15	2046	136	-0.35	0.068	1000	-1000	-0.077	-1000
Visual signal transduction: Cones	15	600	38	-0.095	0.013	1000	-1000	-0.063	-1000
IFN-gamma pathway	15	1030	68	-0.11	0.041	1000	-1000	-0.09	-1000
Syndecan-3-mediated signaling events	15	556	35	-0.17	0.013	1000	-1000	-0.067	-1000
TCGA08_rtk_signaling	15	399	26	-0.25	0.024	1000	-1000	-0.02	-1000
Neurotrophic factor-mediated Trk receptor signaling	15	1863	120	-0.32	0.043	1000	-1000	-0.082	-1000
Aurora B signaling	15	1009	67	-0.38	0.014	1000	-1000	-0.066	-1000
ErbB4 signaling events	14	997	69	-0.14	0.059	1000	-1000	-0.083	-1000
Aurora C signaling	14	103	7	-0.06	0.004	1000	-1000	-0.045	-1000
Nectin adhesion pathway	14	914	63	-0.26	0.037	1000	-1000	-0.076	-1000
FOXM1 transcription factor network	14	758	51	-0.19	0.049	1000	-1000	-0.16	-1000
Presenilin action in Notch and Wnt signaling	12	748	61	-0.21	0.046	1000	-1000	-0.079	-1000
Insulin-mediated glucose transport	12	395	32	-0.21	0.037	1000	-1000	-0.061	-1000
IL1-mediated signaling events	12	803	62	-0.13	0.067	1000	-1000	-0.1	-1000
LPA4-mediated signaling events	11	135	12	-0.12	0.017	1000	-1000	-0.029	-1000
Insulin Pathway	11	819	74	-0.082	0.038	1000	-1000	-0.094	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	11	386	33	-0.17	0.035	1000	-1000	-0.062	-1000
Rapid glucocorticoid signaling	11	226	20	-0.09	0.014	1000	-1000	-0.046	-1000
Class IB PI3K non-lipid kinase events	11	33	3	-0.002	-1000	1000	-1000	-0.015	-1000
Ceramide signaling pathway	10	804	76	-0.18	0.024	1000	-1000	-0.061	-1000
Signaling events mediated by HDAC Class III	10	439	40	-0.36	0.024	1000	-1000	-0.048	-1000
Sphingosine 1-phosphate (S1P) pathway	9	268	28	-0.18	0.032	1000	-1000	-0.06	-1000
a4b1 and a4b7 Integrin signaling	9	48	5	-0.03	0.007	1000	-1000	-0.041	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	9	812	83	-0.21	0.053	1000	-1000	-0.077	-1000
IL2 signaling events mediated by PI3K	9	528	58	-0.06	0.033	1000	-1000	-0.087	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	9	425	45	-0.091	0.039	1000	-1000	-0.087	-1000
Stabilization and expansion of the E-cadherin adherens junction	9	676	74	-0.18	0.087	1000	-1000	-0.085	-1000
IL2 signaling events mediated by STAT5	9	219	22	-0.061	0.042	1000	-1000	-0.048	-1000
Class I PI3K signaling events	9	679	73	-0.26	0.023	1000	-1000	-0.067	-1000
Caspase cascade in apoptosis	8	623	74	-0.091	0.029	1000	-1000	-0.052	-1000
Cellular roles of Anthrax toxin	8	342	39	-0.091	0.019	1000	-1000	-0.035	-1000
Retinoic acid receptors-mediated signaling	8	486	58	-0.12	0.034	1000	-1000	-0.07	-1000
BARD1 signaling events	7	450	57	-0.031	0.054	1000	-1000	-0.065	-1000
mTOR signaling pathway	7	415	53	-0.041	0.023	1000	-1000	-0.061	-1000
Canonical NF-kappaB pathway	6	255	39	-0.091	0.069	1000	-1000	-0.079	-1000
Class I PI3K signaling events mediated by Akt	6	438	68	-0.21	0.052	1000	-1000	-0.066	-1000
TRAIL signaling pathway	6	313	48	-0.085	0.051	1000	-1000	-0.066	-1000
ceramide signaling pathway	6	336	49	-0.091	0.032	1000	-1000	-0.047	-1000
S1P1 pathway	6	235	36	-0.044	0.032	1000	-1000	-0.054	-1000
Regulation of Telomerase	6	711	102	-0.3	0.054	1000	-1000	-0.11	-1000
S1P3 pathway	6	291	42	-0.18	0.05	1000	-1000	-0.053	-1000
Arf6 downstream pathway	5	235	43	-0.17	0.094	1000	-1000	-0.04	-1000
Canonical Wnt signaling pathway	5	270	51	-0.047	0.068	1000	-1000	-0.059	-1000
Effects of Botulinum toxin	5	146	26	-0.18	0.019	1000	-1000	-0.064	-1000
FoxO family signaling	4	316	64	-0.21	0.16	1000	-1000	-0.079	-1000
E-cadherin signaling in the nascent adherens junction	4	326	76	-0.17	0.074	1000	-1000	-0.085	-1000
S1P4 pathway	4	109	25	-0.015	0.032	1000	-1000	-0.049	-1000
Circadian rhythm pathway	3	82	22	-0.053	0.013	1000	-1000	-0.063	-1000
Paxillin-independent events mediated by a4b1 and a4b7	3	133	37	-0.031	0.034	1000	-1000	-0.077	-1000
S1P5 pathway	3	57	17	-0.015	0.024	1000	-1000	-0.052	-1000
Signaling events mediated by HDAC Class I	3	399	104	-0.091	0.061	1000	-1000	-0.071	-1000
Atypical NF-kappaB pathway	3	99	31	-0.029	0.048	1000	-1000	-0.061	-1000
Signaling events mediated by VEGFR1 and VEGFR2	3	460	125	-0.037	0.086	1000	-1000	-0.11	-1000
PLK2 and PLK4 events	2	6	3	0.008	0.021	1000	-1000	-0.017	-1000
Aurora A signaling	2	135	60	-0.052	0.038	1000	-1000	-0.057	-1000
EPO signaling pathway	2	157	55	-0.054	0.065	1000	-1000	-0.1	-1000
PLK1 signaling events	2	243	85	-0.059	0.025	1000	-1000	-0.058	-1000
Paxillin-dependent events mediated by a4b1	2	79	36	-0.03	0.024	1000	-1000	-0.077	-1000
PDGFR-beta signaling pathway	2	254	97	-0.19	0.067	1000	-1000	-0.079	-1000
p38 MAPK signaling pathway	2	120	44	-0.029	0.028	1000	-1000	-0.059	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	1	38	23	-0.031	0.05	1000	-1000	-0.068	-1000
Signaling events mediated by HDAC Class II	1	110	75	-0.049	0.036	1000	-1000	-0.071	-1000
HIF-2-alpha transcription factor network	1	72	43	-0.2	0.21	1000	-1000	-0.083	-1000
Signaling mediated by p38-gamma and p38-delta	1	27	15	0	0.032	1000	-1000	-0.03	-1000
E-cadherin signaling in keratinocytes	1	68	43	-0.005	0.052	1000	-1000	-0.066	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0	0	27	0	0.031	1000	-1000	-0.059	-1000
Arf6 trafficking events	0	65	71	-0.023	0.046	1000	-1000	-0.075	-1000
E-cadherin signaling events	0	0	5	0	0.013	1000	-1000	-0.038	-1000
Arf1 pathway	0	19	54	-0.005	0.036	1000	-1000	-0.045	-1000
Alternative NF-kappaB pathway	0	0	13	0	0.013	1000	-1000	-0.057	-1000
Total	3363	184015	7203	-30	-990	131000	-131000	-9.1	-131000

Ephrin A reverse signaling

Figure S1. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S1. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.46	0.33	-9999	-0.65	288	288
EFNA5	-0.13	0.32	-9999	-0.84	69	69
FYN	-0.41	0.32	-9999	-0.59	288	288
neuron projection morphogenesis	-0.46	0.33	-9999	-0.65	288	288
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.46	0.33	-9999	-0.65	288	288
EPHA5	-0.54	0.41	-9999	-0.85	260	260

×

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

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
MAP4K1	-0.21	0.22	-10000	0	-0.4	234	234
CRKL	-0.21	0.24	-10000	0	-0.42	227	227
HRAS	-0.18	0.21	-10000	0	-0.58	20	20
mol:PIP3	-0.21	0.22	-10000	0	-0.4	227	227
SPRED1	0.013	0	-10000	0	-10000	0	0
SPRED2	0.013	0	-10000	0	-10000	0	0
GAB1	-0.23	0.25	-10000	0	-0.45	227	227
FOXO3	-0.19	0.22	-10000	0	-0.38	227	227
AKT1	-0.21	0.23	-10000	0	-0.41	227	227
BAD	-0.19	0.22	-10000	0	-0.38	227	227
megakaryocyte differentiation	-0.24	0.24	-10000	0	-0.44	234	234
GSK3B	-0.19	0.22	-10000	0	-0.38	227	227
RAF1	-0.14	0.18	-10000	0	-0.47	17	17
SHC1	0.013	0	-10000	0	-10000	0	0
STAT3	-0.23	0.25	-10000	0	-0.45	227	227
STAT1	-0.58	0.58	-10000	0	-1.1	227	227
HRAS/SPRED1	-0.17	0.14	-10000	0	-0.46	18	18
cell proliferation	-0.23	0.25	-10000	0	-0.44	228	228
PIK3CA	0.01	0.043	-10000	0	-0.85	1	1
TEC	0.013	0	-10000	0	-10000	0	0
RPS6KB1	-0.23	0.24	-10000	0	-0.44	227	227
HRAS/SPRED2	-0.17	0.14	-10000	0	-0.46	18	18
LYN/TEC/p62DOK	-0.23	0.2	-10000	0	-0.41	227	227
MAPK3	-0.091	0.13	-10000	0	-0.32	15	15
STAP1	-0.25	0.25	-10000	0	-0.47	227	227
GRAP2	-0.046	0.22	-10000	0	-0.8	30	30
JAK2	-0.5	0.45	-10000	0	-0.9	227	227
STAT1 (dimer)	-0.56	0.57	-10000	0	-1.1	227	227
mol:Gleevec	0.007	0.01	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.24	0.21	-10000	0	-0.42	230	230
actin filament polymerization	-0.22	0.24	-10000	0	-0.44	227	227
LYN	0.013	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.34	0.34	-10000	0	-0.64	227	227
PIK3R1	0.013	0.001	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.21	0.18	-10000	0	-0.42	26	26
PI3K	-0.23	0.21	-10000	0	-0.42	227	227
PTEN	0.011	0.043	-10000	0	-0.85	1	1
SCF/KIT/EPO/EPOR	-0.72	0.72	-10000	0	-1.4	227	227
MAPK8	-0.23	0.25	-10000	0	-0.45	228	228
STAT3 (dimer)	-0.22	0.24	-10000	0	-0.44	227	227
positive regulation of transcription	-0.073	0.11	-10000	0	-0.26	15	15
mol:GDP	-0.22	0.19	-10000	0	-0.56	32	32
PIK3C2B	-0.23	0.25	-10000	0	-0.45	227	227
CBL/CRKL	-0.19	0.22	-10000	0	-0.39	227	227
FER	-0.23	0.25	-10000	0	-0.45	228	228
SH2B3	-0.23	0.25	-10000	0	-0.45	227	227
PDPK1	-0.19	0.21	-10000	0	-0.37	227	227
SNAI2	-0.23	0.25	-10000	0	-0.45	227	227
positive regulation of cell proliferation	-0.4	0.42	-10000	0	-0.77	227	227
KITLG	0.002	0.077	-10000	0	-0.88	3	3
cell motility	-0.4	0.42	-10000	0	-0.77	227	227
PTPN6	0.02	0.018	-10000	0	-10000	0	0
EPOR	-0.13	0.18	-10000	0	-0.67	1	1
STAT5A (dimer)	-0.32	0.34	-10000	0	-0.63	227	227
SOCS1	0.011	0.028	-10000	0	-0.31	3	3
cell migration	0.23	0.25	0.45	228	-10000	0	228
SOS1	0.013	0	-10000	0	-10000	0	0
EPO	-0.002	0.027	-10000	0	-0.33	2	2
VAV1	-0.014	0.11	-10000	0	-0.37	29	29
GRB10	-0.23	0.25	-10000	0	-0.45	227	227
PTPN11	0.016	0.014	-10000	0	-10000	0	0
SCF/KIT	-0.26	0.25	-10000	0	-0.48	227	227
GO:0007205	0.011	0.013	-10000	0	-10000	0	0
MAP2K1	-0.1	0.15	-10000	0	-0.36	15	15
CBL	0.013	0	-10000	0	-10000	0	0
KIT	-0.78	0.76	-10000	0	-1.5	227	227
MAP2K2	-0.1	0.15	-10000	0	-0.36	15	15
SHC/Grb2/SOS1	-0.23	0.2	-10000	0	-0.41	227	227
STAT5A	-0.34	0.36	-10000	0	-0.65	227	227
GRB2	0.013	0	-10000	0	-10000	0	0
response to radiation	-0.23	0.24	-10000	0	-0.44	227	227
SHC/GRAP2	-0.045	0.16	-10000	0	-0.66	27	27
PTPRO	-0.24	0.25	-10000	0	-0.45	234	234
SH2B2	-0.23	0.25	-10000	0	-0.45	227	227
DOK1	0.013	0	-10000	0	-10000	0	0
MATK	-0.24	0.26	-10000	0	-0.46	228	228
CREBBP	0.018	0.02	-10000	0	-10000	0	0
BCL2	-0.2	0.4	-10000	0	-1.6	26	26

×

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	-0.13	0.16	-10000	0	-0.31	174	174
CDKN2C	0.025	0.038	-10000	0	-0.32	2	2
CDKN2A	-0.12	0.16	-10000	0	-0.32	169	169
CCND2	0.07	0.072	0.17	119	-10000	0	119
RB1	-0.068	0.071	-10000	0	-0.17	119	119
CDK4	0.07	0.071	0.17	119	-10000	0	119
CDK6	0.073	0.077	0.18	119	-0.19	1	120
G1/S progression	0.06	0.079	0.17	119	-10000	0	119

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.092	0.071	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.26	0.2	-9999	-0.52	96	96
JUN	-0.33	0.32	-9999	-0.71	134	134
HRAS	0.012	0.023	-9999	-0.31	2	2
RET51/GFRalpha1/GDNF/GRB10	-0.41	0.34	-9999	-0.64	254	254
RAP1A	0.013	0	-9999	-10000	0	0
FRS2	0.013	0	-9999	-10000	0	0
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.41	0.34	-9999	-0.64	254	254
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.31	0.26	-9999	-0.54	234	234
RHOA	0.013	0	-9999	-10000	0	0
RAP1A/GTP	-0.36	0.31	-9999	-0.57	254	254
GRB7	-0.037	0.12	-9999	-0.31	63	63
RET51/GFRalpha1/GDNF	-0.41	0.34	-9999	-0.64	254	254
MAPKKK cascade	-0.32	0.27	-9999	-0.54	185	185
BCAR1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.36	0.32	-9999	-0.6	245	245
lamellipodium assembly	-0.24	0.19	-9999	-0.39	235	235
RET51/GFRalpha1/GDNF/SHC	-0.41	0.34	-9999	-0.64	254	254
PIK3CA	0.011	0.043	-9999	-0.85	1	1
RET9/GFRalpha1/GDNF/SHC	-0.31	0.26	-9999	-0.53	234	234
RET9/GFRalpha1/GDNF/Shank3	-0.31	0.26	-9999	-0.53	234	234
MAPK3	-0.33	0.3	-9999	-0.54	254	254
DOK1	0.013	0	-9999	-10000	0	0
DOK6	-0.13	0.32	-9999	-0.85	68	68
PXN	0.013	0	-9999	-10000	0	0
neurite development	-0.33	0.29	-9999	-0.69	110	110
DOK5	-0.099	0.29	-9999	-0.85	53	53
GFRA1	-0.48	0.43	-9999	-0.85	235	235
MAPK8	-0.24	0.23	-9999	-0.59	72	72
HRAS/GTP	-0.37	0.32	-9999	-0.59	254	254
tube development	-0.29	0.25	-9999	-0.5	234	234
MAPK1	-0.33	0.3	-9999	-0.54	254	254
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.19	0.19	-9999	-0.35	234	234
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.012	0.016	-9999	-0.31	1	1
PDLIM7	0.009	0.036	-9999	-0.31	5	5
RET51/GFRalpha1/GDNF/Dok6	-0.46	0.4	-9999	-0.7	264	264
SHC1	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.41	0.34	-9999	-0.64	254	254
RET51/GFRalpha1/GDNF/Dok5	-0.47	0.4	-9999	-0.71	264	264
PRKCA	-0.038	0.2	-9999	-0.85	24	24
HRAS/GDP	-0.001	0.015	-9999	-10000	0	0
CREB1	-0.25	0.24	-9999	-0.44	234	234
PIK3R1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.19	0.19	-9999	-0.35	234	234
RET51/GFRalpha1/GDNF/Grb7	-0.43	0.34	-9999	-0.66	254	254
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.17	0.33	-9999	-0.85	72	72
DOK4	0.013	0	-9999	-10000	0	0
JNK cascade	-0.32	0.31	-9999	-0.69	134	134
RET9/GFRalpha1/GDNF/FRS2	-0.31	0.26	-9999	-0.53	234	234
SHANK3	0.013	0	-9999	-10000	0	0
RASA1	0.013	0	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.19	0.19	-9999	-0.35	234	234
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.26	0.24	-9999	-0.44	203	203
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.26	0.24	-9999	-0.42	254	254
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.3	0.32	-9999	-0.86	70	70
PI3K	-0.38	0.34	-9999	-0.63	235	235
SOS1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.29	0.25	-9999	-0.5	234	234
GRB10	0.013	0	-9999	-10000	0	0
activation of MAPKK activity	-0.23	0.21	-9999	-0.54	69	69
RET51/GFRalpha1/GDNF/FRS2	-0.41	0.34	-9999	-0.64	254	254
GAB1	0.013	0	-9999	-10000	0	0
IRS1	-0.078	0.26	-9999	-0.85	43	43
IRS2	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.3	0.32	-9999	-0.87	69	69
RET51/GFRalpha1/GDNF/PKC alpha	-0.43	0.38	-9999	-0.68	254	254
GRB2	0.013	0	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
GDNF	-0.001	0.039	-9999	-0.31	6	6
RAC1	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.46	0.38	-9999	-0.69	264	264
Rac1/GTP	-0.3	0.23	-9999	-0.47	235	235
RET9/GFRalpha1/GDNF	-0.34	0.29	-9999	-0.58	234	234
GFRalpha1/GDNF	-0.38	0.33	-9999	-0.66	234	234

×

Reelin signaling pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	-0.001	0.014	-9999	-10000	0	0
VLDLR	-0.012	0.15	-9999	-0.85	12	12
CRKL	0.013	0	-9999	-10000	0	0
LRPAP1	0.013	0	-9999	-10000	0	0
FYN	0.013	0	-9999	-10000	0	0
ITGA3	0.009	0.036	-9999	-0.31	5	5
RELN/VLDLR/Fyn	-0.44	0.27	-9999	-0.59	307	307
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.004	0.041	-9999	-0.48	3	3
AKT1	-0.24	0.17	-9999	-0.66	11	11
MAP2K7	0.013	0	-9999	-10000	0	0
RAPGEF1	0.013	0	-9999	-10000	0	0
DAB1	0.007	0.007	-9999	-10000	0	0
RELN/LRP8/DAB1	-0.42	0.26	-9999	-0.55	307	307
LRPAP1/LRP8	-0.026	0.13	-9999	-0.66	16	16
RELN/LRP8/DAB1/Fyn	-0.39	0.24	-9999	-0.52	307	307
DAB1/alpha3/beta1 Integrin	-0.36	0.24	-9999	-0.48	309	309
long-term memory	-0.39	0.25	-9999	-0.51	309	309
DAB1/LIS1	-0.37	0.24	-9999	-0.5	309	309
DAB1/CRLK/C3G	-0.36	0.23	-9999	-0.48	309	309
PIK3CA	0.011	0.043	-9999	-0.85	1	1
DAB1/NCK2	-0.38	0.24	-9999	-0.5	309	309
ARHGEF2	0.013	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.026	0.17	-9999	-0.65	24	24
CDK5R1	0.012	0.023	-9999	-0.31	2	2
RELN	-0.63	0.38	-9999	-0.85	305	305
PIK3R1	0.013	0	-9999	-10000	0	0
RELN/LRP8/Fyn	-0.44	0.27	-9999	-0.59	307	307
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.4	0.26	-9999	-0.54	309	309
MAPK8	0.007	0.074	-9999	-0.85	3	3
RELN/VLDLR/DAB1	-0.41	0.25	-9999	-0.55	307	307
ITGB1	0.013	0	-9999	-10000	0	0
MAP1B	-0.39	0.26	-9999	-0.52	309	309
RELN/LRP8	-0.44	0.27	-9999	-0.59	307	307
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.39	0.24	-9999	-0.52	307	307
PI3K	-0.002	0.032	-9999	-0.66	1	1
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.002	0.022	-9999	-10000	0	0
RAP1A	-0.32	0.24	-9999	-0.83	23	23
PAFAH1B1	0.013	0	-9999	-10000	0	0
MAPK8IP1	0.013	0	-9999	-10000	0	0
CRLK/C3G	0	0	-9999	-10000	0	0
GRIN2B	0.003	0.017	-9999	-0.31	1	1
NCK2	0.013	0	-9999	-10000	0	0
neuron differentiation	-0.16	0.13	-9999	-0.51	16	16
neuron adhesion	-0.3	0.23	-9999	-0.74	27	27
LRP8	-0.021	0.17	-9999	-0.85	16	16
GSK3B	-0.22	0.16	-9999	-0.62	11	11
RELN/VLDLR/DAB1/Fyn	-0.38	0.23	-9999	-0.51	307	307
MAP3K11	0.013	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.26	0.18	-9999	-0.36	307	307
CDK5	0.013	0	-9999	-10000	0	0
MAPT	0.034	0.087	-9999	-0.32	18	18
neuron migration	-0.31	0.22	-9999	-0.43	306	306
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.16	0.13	-9999	-0.52	16	16
RELN/VLDLR	-0.42	0.27	-9999	-0.56	309	309

×

Wnt signaling

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
Noncanonical Wnts/FZD	-0.3	0.29	-9999	-0.48	261	261
FZD6	0.013	0	-9999	-10000	0	0
WNT6	0.005	0.048	-9999	-0.31	9	9
WNT4	-0.28	0.41	-9999	-0.84	142	142
FZD3	0.013	0	-9999	-10000	0	0
WNT5A	-0.009	0.13	-9999	-0.8	11	11
WNT11	-0.44	0.43	-9999	-0.85	214	214

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	-0.047	0.17	-10000	0	-0.51	35	35
NFATC2	-0.22	0.38	-10000	0	-0.86	85	85
NFATC3	-0.084	0.13	-10000	0	-10000	0	0
CD40LG	-0.73	0.58	-10000	0	-1.2	223	223
ITCH	0.051	0.016	-10000	0	-10000	0	0
CBLB	0.051	0.016	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.51	0.52	-10000	0	-1.2	109	109
JUNB	0	0.1	-10000	0	-0.85	6	6
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.001	0.017	-10000	0	-0.34	1	1
T cell anergy	0.029	0.065	-10000	0	-0.5	1	1
TLE4	-0.23	0.44	-10000	0	-0.93	99	99
Jun/NFAT1-c-4/p21SNFT	-0.66	0.62	-10000	0	-1.2	196	196
AP-1/NFAT1-c-4	-0.9	0.8	-10000	0	-1.5	221	221
IKZF1	-0.16	0.34	-10000	0	-0.78	74	74
T-helper 2 cell differentiation	-0.3	0.34	-10000	0	-0.85	90	90
AP-1/NFAT1	-0.42	0.5	-10000	0	-0.95	170	170
CALM1	0.028	0.01	-10000	0	-10000	0	0
EGR2	-0.77	0.86	-10000	0	-1.7	184	184
EGR3	-0.56	0.75	-10000	0	-1.6	118	118
NFAT1/FOXP3	-0.2	0.34	-10000	0	-0.73	94	94
EGR1	-0.18	0.36	-10000	0	-0.85	89	89
JUN	-0.2	0.36	-10000	0	-0.86	93	93
EGR4	-0.049	0.21	-10000	0	-0.74	32	32
mol:Ca2+	0.016	0.011	-10000	0	-10000	0	0
GBP3	-0.15	0.32	-10000	0	-0.81	58	58
FOSL1	-0.036	0.12	-10000	0	-0.31	62	62
NFAT1-c-4/MAF/IRF4	-0.55	0.56	-10000	0	-1.1	194	194
DGKA	-0.14	0.3	-10000	0	-0.72	65	65
CREM	0.013	0	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.54	0.56	-10000	0	-1.1	195	195
CTLA4	-0.22	0.38	-10000	0	-0.86	86	86
NFAT1-c-4 (dimer)/EGR1	-0.63	0.68	-10000	0	-1.3	193	193
NFAT1-c-4 (dimer)/EGR4	-0.57	0.57	-10000	0	-1.1	198	198
FOS	-0.22	0.38	-10000	0	-0.86	106	106
IFNG	-0.42	0.55	-10000	0	-1.2	117	117
T cell activation	-0.43	0.43	-10000	0	-0.98	132	132
MAF	0.013	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	0.35	0.42	0.8	149	-10000	0	149
TNF	-0.59	0.59	-10000	0	-1.1	195	195
FASLG	-0.73	0.8	-10000	0	-1.5	199	199
TBX21	-0.04	0.19	-10000	0	-0.72	26	26
BATF3	-0.009	0.089	-10000	0	-0.33	26	26
PRKCQ	0	0.1	-10000	0	-0.85	6	6
PTPN1	-0.14	0.29	-10000	0	-0.71	68	68
NFAT1-c-4/ICER1	-0.53	0.56	-10000	0	-1.1	193	193
GATA3	-0.036	0.2	-10000	0	-0.83	24	24
T-helper 1 cell differentiation	-0.4	0.52	-10000	0	-1.1	119	119
IL2RA	-0.46	0.46	-10000	0	-1	117	117
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.14	0.29	-10000	0	-0.7	69	69
E2F1	-0.082	0.15	-10000	0	-10000	0	0
PPARG	-0.001	0.1	-10000	0	-0.58	10	10
SLC3A2	-0.14	0.29	-10000	0	-0.74	58	58
IRF4	-0.099	0.23	-10000	0	-0.46	98	98
PTGS2	-0.71	0.58	-10000	0	-1.2	215	215
CSF2	-0.77	0.54	-10000	0	-1.2	221	221
JunB/Fra1/NFAT1-c-4	-0.53	0.54	-10000	0	-1	189	189
IL4	-0.31	0.37	-10000	0	-0.93	84	84
IL5	-0.69	0.55	-10000	0	-1.2	212	212
IL2	-0.44	0.45	-10000	0	-1	132	132
IL3	-0.096	0.063	-10000	0	-10000	0	0
RNF128	0.049	0.047	-10000	0	-0.9	1	1
NFATC1	-0.35	0.42	-10000	0	-0.81	146	146
CDK4	0.21	0.24	0.57	64	-10000	0	64
PTPRK	-0.14	0.29	-10000	0	-0.74	58	58
IL8	-0.72	0.56	-10000	0	-1.2	213	213
POU2F1	0.013	0.016	-10000	0	-0.31	1	1

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.11	0.3	-9999	-0.85	59	59
GNB1/GNG2	-0.27	0.24	-9999	-0.62	109	109
mol:DAG	-0.23	0.24	-9999	-0.57	102	102
PLCG1	-0.24	0.25	-9999	-0.59	102	102
YES1	-0.27	0.28	-9999	-0.45	261	261
FZD3	0.013	0	-9999	-10000	0	0
FZD6	0.013	0	-9999	-10000	0	0
G protein	-0.26	0.23	-9999	-0.6	102	102
MAP3K7	-0.18	0.21	-9999	-0.46	103	103
mol:Ca2+	-0.22	0.24	-9999	-0.55	102	102
mol:IP3	-0.23	0.24	-9999	-0.57	102	102
NLK	-0.011	0.01	-9999	-10000	0	0
GNB1	0.013	0	-9999	-10000	0	0
CAMK2A	-0.21	0.22	-9999	-0.51	103	103
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.3	0.29	-9999	-0.48	261	261
CSNK1A1	0.013	0	-9999	-10000	0	0
GNAS	-0.27	0.28	-9999	-0.61	122	122
GO:0007205	-0.22	0.24	-9999	-0.56	102	102
WNT6	0.005	0.048	-9999	-0.31	9	9
WNT4	-0.28	0.41	-9999	-0.84	142	142
NFAT1/CK1 alpha	-0.31	0.26	-9999	-0.6	151	151
GNG2	0.013	0	-9999	-10000	0	0
WNT5A	-0.009	0.13	-9999	-0.8	11	11
WNT11	-0.44	0.43	-9999	-0.85	214	214
CDC42	-0.25	0.26	-9999	-0.6	109	109

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.55	0.56	-9999	-1.1	190	190
PCK1	-0.37	0.52	-9999	-1.5	59	59
HNF4A	-0.71	0.67	-9999	-1.3	208	208
KCNJ11	-0.52	0.56	-9999	-1.1	165	165
AKT1	-0.042	0.13	-9999	-10000	0	0
response to starvation	-0.017	0.034	-9999	-10000	0	0
DLK1	-0.52	0.55	-9999	-1.1	177	177
NKX2-1	-0.17	0.21	-9999	-10000	0	0
ACADM	-0.55	0.56	-9999	-1.1	190	190
TAT	-0.21	0.23	-9999	-0.6	21	21
CEBPB	0.013	0.004	-9999	-10000	0	0
CEBPA	0.005	0.085	-9999	-0.85	4	4
TTR	-0.2	0.22	-9999	-0.78	25	25
PKLR	-0.55	0.56	-9999	-1.1	191	191
APOA1	-0.97	0.91	-9999	-1.8	217	217
CPT1C	-0.56	0.56	-9999	-1.1	178	178
ALAS1	-0.17	0.21	-9999	-10000	0	0
TFRC	-0.27	0.29	-9999	-0.73	29	29
FOXF1	-0.009	0.086	-9999	-0.86	4	4
NF1	0.021	0.001	-9999	-10000	0	0
HNF1A (dimer)	0.013	0.043	-9999	-0.85	1	1
CPT1A	-0.55	0.56	-9999	-1.1	183	183
HMGCS1	-0.55	0.56	-9999	-1.1	182	182
NR3C1	0.019	0.015	-9999	-10000	0	0
CPT1B	-0.55	0.56	-9999	-1.1	190	190
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.013	0.005	-9999	-10000	0	0
GCK	-0.7	0.72	-9999	-1.3	206	206
CREB1	-0.002	0.055	-9999	-10000	0	0
IGFBP1	-0.19	0.2	-9999	-0.58	3	3
PDX1	-0.19	0.22	-9999	-0.86	2	2
UCP2	-0.55	0.56	-9999	-1.1	192	192
ALDOB	-0.52	0.55	-9999	-1.1	167	167
AFP	-0.047	0.12	-9999	-0.46	12	12
BDH1	-0.55	0.56	-9999	-1.1	180	180
HADH	-0.51	0.55	-9999	-1.1	174	174
F2	-0.66	0.65	-9999	-1.3	179	179
HNF1A	0.013	0.043	-9999	-0.85	1	1
G6PC	-0.008	0.092	-9999	-10000	0	0
SLC2A2	-0.24	0.27	-9999	-0.55	77	77
INS	-0.008	0.018	-9999	-10000	0	0
FOXA1	-0.055	0.14	-9999	-0.35	66	66
FOXA3	-0.077	0.18	-9999	-0.39	67	67
FOXA2	-0.59	0.63	-9999	-1.2	190	190
ABCC8	-0.83	0.78	-9999	-1.4	229	229
ALB	-0.1	0.34	-9999	-1.3	28	28

×

PDGFR-alpha signaling pathway

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
PDGFRA	-0.26	0.4	-9999	-0.86	126	126
PDGF/PDGFRA/CRKL	-0.2	0.3	-9999	-0.65	126	126
positive regulation of JUN kinase activity	-0.16	0.23	-9999	-0.5	126	126
CRKL	0.013	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.21	0.3	-9999	-0.66	126	126
AP1	-0.51	0.64	-9999	-1.5	110	110
mol:IP3	-0.2	0.32	-9999	-0.68	126	126
PLCG1	-0.2	0.32	-9999	-0.68	126	126
PDGF/PDGFRA/alphaV Integrin	-0.2	0.3	-9999	-0.66	126	126
RAPGEF1	0.013	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
mol:Ca2+	-0.2	0.32	-9999	-0.67	126	126
CAV3	-0.002	0.035	-9999	-0.31	5	5
CAV1	-0.01	0.14	-9999	-0.85	11	11
SHC/Grb2/SOS1	-0.16	0.24	-9999	-0.51	126	126
PDGF/PDGFRA/Shf	-0.2	0.3	-9999	-0.65	126	126
FOS	-0.46	0.62	-9999	-1.4	110	110
JUN	-0.18	0.3	-9999	-0.73	93	93
oligodendrocyte development	-0.2	0.3	-9999	-0.66	126	126
GRB2	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
mol:DAG	-0.2	0.32	-9999	-0.68	126	126
PDGF/PDGFRA	-0.26	0.4	-9999	-0.86	126	126
actin cytoskeleton reorganization	-0.2	0.3	-9999	-0.65	126	126
SRF	0.033	0.012	-9999	-10000	0	0
SHC1	0.013	0	-9999	-10000	0	0
PI3K	-0.17	0.26	-9999	-0.56	127	127
PDGF/PDGFRA/Crk/C3G	-0.17	0.26	-9999	-0.56	126	126
JAK1	-0.19	0.31	-9999	-0.65	126	126
ELK1/SRF	-0.15	0.24	-9999	-0.51	126	126
SHB	0.013	0	-9999	-10000	0	0
SHF	0.012	0.016	-9999	-0.31	1	1
CSNK2A1	0.027	0.028	-9999	-10000	0	0
GO:0007205	-0.21	0.32	-9999	-0.69	126	126
SOS1	0.013	0	-9999	-10000	0	0
Ras protein signal transduction	-0.16	0.23	-9999	-0.5	126	126
PDGF/PDGFRA/SHB	-0.2	0.3	-9999	-0.65	126	126
PDGF/PDGFRA/Caveolin-1	-0.22	0.32	-9999	-0.68	131	131
ITGAV	0.011	0.043	-9999	-0.85	1	1
ELK1	-0.19	0.29	-9999	-0.62	126	126
PIK3CA	0.011	0.043	-9999	-0.85	1	1
PDGF/PDGFRA/Crk	-0.2	0.3	-9999	-0.65	126	126
JAK-STAT cascade	-0.19	0.31	-9999	-0.65	126	126
cell proliferation	-0.2	0.3	-9999	-0.65	126	126

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.59	0.44	-10000	0	-1.1	138	138
STAT6 (cleaved dimer)	-0.65	0.45	-10000	0	-1	192	192
IGHG1	-0.2	0.14	-10000	0	-0.37	11	11
IGHG3	-0.58	0.43	-10000	0	-0.99	172	172
AKT1	-0.32	0.26	-10000	0	-0.7	72	72
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.26	0.26	-10000	0	-0.72	53	53
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.35	0.28	-10000	0	-0.71	97	97
THY1	-0.59	0.45	-10000	0	-1.1	118	118
MYB	-0.009	0.13	-10000	0	-0.68	13	13
HMGA1	0.013	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.42	0.32	-10000	0	-0.75	138	138
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.32	0.26	-10000	0	-0.72	61	61
SP1	0.02	0.006	-10000	0	-10000	0	0
INPP5D	-0.005	0.075	-10000	0	-0.31	23	23
SOCS5	0.03	0.013	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.62	0.44	-10000	0	-1	177	177
SOCS1	-0.4	0.29	-10000	0	-0.73	104	104
SOCS3	-0.4	0.39	-10000	0	-1.1	67	67
FCER2	-0.58	0.43	-10000	0	-0.97	181	181
PARP14	0.012	0.004	-10000	0	-10000	0	0
CCL17	-0.67	0.49	-10000	0	-1.1	169	169
GRB2	0.013	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.26	0.22	-10000	0	-0.69	38	38
T cell proliferation	-0.6	0.46	-10000	0	-1.1	130	130
IL4R/JAK1	-0.59	0.44	-10000	0	-1.2	106	106
EGR2	-0.92	0.73	-10000	0	-1.6	199	199
JAK2	-0.015	0.024	-10000	0	-10000	0	0
JAK3	-0.06	0.14	-10000	0	-0.31	94	94
PIK3R1	0.013	0	-10000	0	-10000	0	0
JAK1	0.002	0.009	-10000	0	-10000	0	0
COL1A2	-0.19	0.16	-10000	0	-0.55	17	17
CCL26	-0.61	0.46	-10000	0	-1.1	130	130
IL4R	-0.63	0.47	-10000	0	-1.2	106	106
PTPN6	0.028	0.009	-10000	0	-10000	0	0
IL13RA2	-0.71	0.58	-10000	0	-1.4	138	138
IL13RA1	-0.015	0.024	-10000	0	-10000	0	0
IRF4	-0.34	0.47	-10000	0	-1.2	79	79
ARG1	-0.14	0.12	-10000	0	-10000	0	0
CBL	-0.38	0.3	-10000	0	-0.75	110	110
GTF3A	0.016	0.01	-10000	0	-10000	0	0
PIK3CA	0.011	0.043	-10000	0	-0.85	1	1
IL13RA1/JAK2	-0.022	0.034	-10000	0	-10000	0	0
IRF4/BCL6	-0.31	0.43	-10000	0	-1.1	69	69
CD40LG	-0.12	0.32	-10000	0	-0.83	68	68
MAPK14	-0.4	0.33	-10000	0	-0.79	114	114
mitosis	-0.3	0.25	-10000	0	-0.66	70	70
STAT6	-0.68	0.52	-10000	0	-1.2	154	154
SPI1	0.002	0.069	-10000	0	-0.31	19	19
RPS6KB1	-0.29	0.24	-10000	0	-0.67	53	53
STAT6 (dimer)	-0.68	0.52	-10000	0	-1.2	154	154
STAT6 (dimer)/PARP14	-0.63	0.48	-10000	0	-1.1	152	152
mast cell activation	0.016	0.01	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.32	0.28	-10000	0	-0.74	68	68
FRAP1	-0.32	0.26	-10000	0	-0.7	72	72
LTA	-0.62	0.46	-10000	0	-1.2	120	120
FES	0.013	0	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0.66	0.5	1.2	155	-10000	0	155
CCL11	-0.59	0.44	-10000	0	-1.1	131	131
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.32	0.27	-10000	0	-0.72	71	71
IL2RG	-0.044	0.2	-10000	0	-0.85	20	20
IL10	-0.61	0.48	-10000	0	-1.2	125	125
IRS1	-0.078	0.26	-10000	0	-0.85	43	43
IRS2	0.013	0	-10000	0	-10000	0	0
IL4	-0.14	0.098	-10000	0	-10000	0	0
IL5	-0.6	0.44	-10000	0	-1.1	138	138
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.48	0.34	-10000	0	-0.84	138	138
COL1A1	-0.26	0.23	-10000	0	-1.7	3	3
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.6	0.46	-10000	0	-1.2	101	101
IL2R gamma/JAK3	-0.077	0.18	-10000	0	-0.53	43	43
TFF3	-1.3	0.62	-10000	0	-1.6	328	328
ALOX15	-0.6	0.45	-10000	0	-1.2	112	112
MYBL1	0.012	0.016	-10000	0	-0.31	1	1
T-helper 2 cell differentiation	-0.51	0.36	-10000	0	-0.87	162	162
SHC1	0.013	0	-10000	0	-10000	0	0
CEBPB	0.017	0.004	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.3	0.26	-10000	0	-0.67	68	68
mol:PI-3-4-5-P3	-0.32	0.26	-10000	0	-0.7	72	72
PI3K	-0.33	0.28	-10000	0	-0.75	72	72
DOK2	0.001	0.078	-10000	0	-0.4	12	12
ETS1	0.029	0.01	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.24	0.21	-10000	0	-0.67	38	38
ITGB3	-0.62	0.48	-10000	0	-1.2	134	134
PIGR	-0.64	0.5	-10000	0	-1.3	119	119
IGHE	0.051	0.036	-10000	0	-10000	0	0
MAPKKK cascade	-0.24	0.21	-10000	0	-0.66	38	38
BCL6	0.011	0.043	-10000	0	-0.85	1	1
OPRM1	-0.6	0.44	-10000	0	-1.1	120	120
RETNLB	-0.6	0.44	-10000	0	-1.1	125	125
SELP	-0.6	0.46	-10000	0	-1.1	126	126
AICDA	-0.58	0.43	-10000	0	-1.1	130	130

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.012	0.001	-10000	0	-10000	0	0
GNB1/GNG2	-0.22	0.26	-10000	0	-0.53	170	170
regulation of S phase of mitotic cell cycle	-0.13	0.18	-10000	0	-0.34	171	171
GNAO1	-0.016	0.15	-10000	0	-0.72	16	16
HRAS	0.011	0.023	-10000	0	-0.31	2	2
SHBG/T-DHT	-0.011	0.081	-10000	0	-0.59	8	8
PELP1	0.013	0.001	-10000	0	-10000	0	0
AKT1	0.012	0.001	-10000	0	-10000	0	0
MAP2K1	-0.17	0.24	-10000	0	-0.45	170	170
T-DHT/AR	-0.28	0.33	-10000	0	-0.67	170	170
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	-10000	0	-0.005	106	106
GNAI2	0.013	0	-10000	0	-10000	0	0
GNAI3	0.013	0	-10000	0	-10000	0	0
GNAI1	0.013	0	-10000	0	-10000	0	0
mol:GDP	-0.27	0.31	-10000	0	-0.64	170	170
cell proliferation	-0.2	0.28	-10000	0	-0.67	67	67
PIK3CA	0.011	0.043	-10000	0	-0.85	1	1
FOS	-0.25	0.39	-10000	0	-0.89	106	106
mol:Ca2+	-0.027	0.03	-10000	0	-0.071	71	71
MAPK3	-0.19	0.26	-10000	0	-0.47	170	170
MAPK1	-0.084	0.13	-10000	0	-0.31	59	59
PIK3R1	0.013	0	-10000	0	-10000	0	0
mol:IP3	-0.001	0.002	-10000	0	-0.004	106	106
cAMP biosynthetic process	0.014	0.084	-10000	0	-0.55	8	8
GNG2	0.013	0	-10000	0	-10000	0	0
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.004	106	106
HRAS/GTP	-0.21	0.24	-10000	0	-0.49	170	170
actin cytoskeleton reorganization	-0.001	0.023	-10000	0	-0.46	1	1
SRC	0.012	0.017	-10000	0	-0.32	1	1
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.004	106	106
PI3K	-0.001	0.029	-10000	0	-0.58	1	1
apoptosis	0.16	0.25	0.52	106	-10000	0	106
T-DHT/AR/PELP1	-0.24	0.29	-10000	0	-0.58	170	170
HRAS/GDP	-0.25	0.3	-10000	0	-0.6	171	171
CREB1	-0.18	0.27	-10000	0	-0.57	106	106
RAC1-CDC42/GTP	-0.001	0.023	-10000	0	-0.47	1	1
AR	-0.35	0.43	-10000	0	-0.85	170	170
GNB1	0.013	0	-10000	0	-10000	0	0
RAF1	-0.18	0.25	-10000	0	-0.47	170	170
RAC1-CDC42/GDP	-0.24	0.28	-10000	0	-0.57	170	170
T-DHT/AR/PELP1/Src	-0.22	0.26	-10000	0	-0.54	170	170
MAP2K2	-0.17	0.24	-10000	0	-0.45	170	170
T-DHT/AR/PELP1/Src/PI3K	-0.13	0.19	-10000	0	-0.35	171	171
GNAZ	0.013	0	-10000	0	-10000	0	0
SHBG	-0.004	0.12	-10000	0	-0.85	8	8
Gi family/GNB1/GNG2/GDP	-0.018	0.11	-10000	0	-0.54	12	12
mol:T-DHT	0	0.001	0.002	59	-0.003	46	105
RAC1	0.013	0	-10000	0	-10000	0	0
GNRH1	0.01	0.034	-10000	0	-0.67	1	1
Gi family/GTP	-0.095	0.12	-10000	0	-0.48	12	12
CDC42	0.013	0	-10000	0	-10000	0	0

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.12	0.27	-10000	0	-0.71	29	29
IHH	-0.22	0.39	-10000	0	-0.87	108	108
SHH Np/Cholesterol/GAS1	-0.11	0.22	-10000	0	-0.54	82	82
LRPAP1	0.013	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.11	0.21	0.54	82	-10000	0	82
SMO/beta Arrestin2	-0.11	0.25	-10000	0	-0.5	109	109
SMO	-0.12	0.26	-10000	0	-0.53	110	110
AKT1	-0.029	0.12	-10000	0	-10000	0	0
ARRB2	0.013	0	-10000	0	-10000	0	0
BOC	-0.004	0.12	-10000	0	-0.85	8	8
ADRBK1	0.013	0	-10000	0	-10000	0	0
heart looping	-0.12	0.26	-10000	0	-0.52	110	110
STIL	-0.087	0.2	-10000	0	-0.59	16	16
DHH N/PTCH2	-0.11	0.25	-10000	0	-0.66	68	68
DHH N/PTCH1	-0.11	0.24	-10000	0	-0.48	112	112
PIK3CA	0.011	0.043	-10000	0	-0.85	1	1
DHH	0.007	0.074	-10000	0	-0.85	3	3
PTHLH	-0.17	0.38	-10000	0	-1.2	29	29
determination of left/right symmetry	-0.12	0.26	-10000	0	-0.52	110	110
PIK3R1	0.013	0	-10000	0	-10000	0	0
skeletal system development	-0.17	0.37	-10000	0	-1.2	29	29
IHH N/Hhip	-0.41	0.42	-10000	0	-0.77	221	221
DHH N/Hhip	-0.26	0.32	-10000	0	-0.66	160	160
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.12	0.26	-10000	0	-0.52	110	110
pancreas development	-0.33	0.42	-10000	0	-0.84	161	161
HHAT	0.011	0.043	-10000	0	-0.85	1	1
PI3K	-0.002	0.032	-10000	0	-0.66	1	1
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.16	0.34	-10000	0	-0.85	81	81
somite specification	-0.12	0.26	-10000	0	-0.52	110	110
SHH Np/Cholesterol/PTCH1	-0.099	0.21	-10000	0	-0.64	15	15
SHH Np/Cholesterol/PTCH2	-0.092	0.2	-10000	0	-0.54	67	67
SHH Np/Cholesterol/Megalin	-0.14	0.23	-10000	0	-0.54	102	102
SHH	0.007	0.052	-10000	0	-0.66	1	1
catabolic process	-0.13	0.26	-10000	0	-0.53	109	109
SMO/Vitamin D3	-0.1	0.23	-10000	0	-0.68	15	15
SHH Np/Cholesterol/Hhip	-0.21	0.26	-10000	0	-0.53	160	160
LRP2	-0.2	0.37	-10000	0	-0.85	101	101
receptor-mediated endocytosis	-0.2	0.24	-10000	0	-0.74	38	38
SHH Np/Cholesterol/BOC	-0.016	0.084	-10000	0	-0.55	9	9
SHH Np/Cholesterol/CDO	-0.16	0.24	-10000	0	-0.54	119	119
mesenchymal cell differentiation	0.21	0.26	0.53	160	-10000	0	160
mol:Vitamin D3	-0.098	0.22	-10000	0	-0.65	15	15
IHH N/PTCH2	-0.25	0.36	-10000	0	-0.69	154	154
CDON	-0.24	0.39	-10000	0	-0.85	118	118
IHH N/PTCH1	-0.13	0.26	-10000	0	-0.54	109	109
Megalin/LRPAP1	-0.16	0.28	-10000	0	-0.66	101	101
PTCH2	-0.13	0.32	-10000	0	-0.85	66	66
SHH Np/Cholesterol	-0.006	0.038	-10000	0	-0.54	1	1
PTCH1	-0.13	0.26	-10000	0	-0.54	109	109
HHIP	-0.33	0.42	-10000	0	-0.84	161	161

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.013	0	-9999	-10000	0	0
VLDLR	-0.012	0.15	-9999	-0.85	12	12
LRPAP1	0.013	0	-9999	-10000	0	0
NUDC	0.013	0	-9999	-10000	0	0
RELN/LRP8	-0.44	0.27	-9999	-0.59	307	307
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0.013	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.4	0.26	-9999	-0.54	307	307
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	0.007	0.007	-9999	-10000	0	0
IQGAP1	0.013	0	-9999	-10000	0	0
PLA2G7	-0.12	0.31	-9999	-0.85	61	61
CALM1	0.013	0	-9999	-10000	0	0
DYNLT1	0.013	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.026	0.13	-9999	-0.66	16	16
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.013	0	-9999	-10000	0	0
CDK5R1	0.012	0.023	-9999	-0.31	2	2
LIS1/Poliovirus Protein 3A	0	0	-9999	-10000	0	0
CDK5R2	0.004	0.023	-9999	-0.31	2	2
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.44	0.27	-9999	-0.59	307	307
YWHAE	0.013	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.29	0.21	-9999	-0.76	14	14
MAP1B	0	0.005	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.34	0.24	-9999	-0.47	307	307
RELN	-0.63	0.38	-9999	-0.85	305	305
PAFAH/LIS1	-0.061	0.21	-9999	-0.57	61	61
LIS1/CLIP170	0.028	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.24	0.14	-9999	-0.56	14	14
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.25	0.18	-9999	-0.34	308	308
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.32	0.22	-9999	-0.44	307	307
LIS1/IQGAP1	0.028	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.024	0	-9999	-10000	0	0
PAFAH1B3	0.012	0.023	-9999	-0.31	2	2
PAFAH1B2	0.009	0.06	-9999	-0.85	2	2
MAP1B/LIS1/Dynein heavy chain	0.026	0.004	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.29	0.18	-9999	-0.72	14	14
LRP8	-0.021	0.17	-9999	-0.85	16	16
NDEL1/Katanin 60	-0.29	0.21	-9999	-0.73	15	15
P39/CDK5	-0.34	0.24	-9999	-0.47	307	307
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.028	0	-9999	-10000	0	0
CDK5	-0.36	0.25	-9999	-0.5	307	307
PPP2R5D	0.013	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0	-9999	-10000	0	0
CSNK2A1	0.013	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.38	0.23	-9999	-0.5	307	307
RELN/VLDLR	-0.42	0.27	-9999	-0.56	309	309
CDC42	0	0	-9999	-10000	0	0

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.009	0.076	-9999	-0.59	6	6
NFATC2	-0.09	0.21	-9999	-0.61	59	59
NFATC3	0	0.028	-9999	-10000	0	0
CD40LG	-0.44	0.42	-9999	-0.89	169	169
PTGS2	-0.42	0.41	-9999	-0.87	156	156
JUNB	0	0.1	-9999	-0.85	6	6
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.006	0.014	-9999	-10000	0	0
CaM/Ca2+	-0.006	0.014	-9999	-10000	0	0
CALM1	0.008	0.008	-9999	-10000	0	0
JUN	-0.19	0.36	-9999	-0.86	93	93
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	-0.036	0.12	-9999	-0.31	62	62
CREM	0.013	0	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.26	0.28	-9999	-0.6	135	135
FOS	-0.22	0.38	-9999	-0.86	106	106
IFNG	-0.44	0.41	-9999	-0.86	172	172
AP-1/NFAT1-c-4	-0.53	0.52	-9999	-1	174	174
FASLG	-0.42	0.4	-9999	-0.85	161	161
NFAT1-c-4/ICER1	-0.11	0.2	-9999	-0.54	64	64
IL2RA	-0.41	0.39	-9999	-0.84	154	154
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	-0.48	0.37	-9999	-0.82	191	191
JunB/Fra1/NFAT1-c-4	-0.13	0.2	-9999	-0.54	67	67
IL4	-0.4	0.37	-9999	-0.81	154	154
IL2	-0.013	0.026	-9999	-10000	0	0
IL3	-0.032	0.031	-9999	-10000	0	0
FKBP1A	0.013	0	-9999	-10000	0	0
BATF3	-0.009	0.089	-9999	-0.33	26	26
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.013	0.016	-9999	-0.31	1	1

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0.16	0.3	0.7	95	-10000	0	95
KIRREL	-0.06	0.22	-10000	0	-0.87	29	29
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.16	0.3	-10000	0	-0.7	95	95
PLCG1	0.013	0	-10000	0	-10000	0	0
ARRB2	0.013	0	-10000	0	-10000	0	0
WASL	0.013	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.13	0.24	-10000	0	-0.54	95	95
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.071	0.19	-10000	0	-0.4	95	95
FYN	-0.11	0.23	-10000	0	-0.51	95	95
mol:Ca2+	-0.12	0.23	-10000	0	-0.53	95	95
mol:DAG	-0.12	0.23	-10000	0	-0.54	95	95
NPHS2	-0.014	0.034	-10000	0	-10000	0	0
mol:IP3	-0.12	0.23	-10000	0	-0.54	95	95
regulation of endocytosis	-0.11	0.21	-10000	0	-0.48	95	95
Nephrin/NEPH1/podocin/Cholesterol	-0.13	0.24	-10000	0	-0.55	95	95
establishment of cell polarity	-0.16	0.3	-10000	0	-0.7	95	95
Nephrin/NEPH1/podocin/NCK1-2	-0.12	0.22	-10000	0	-0.49	95	95
Nephrin/NEPH1/beta Arrestin2	-0.11	0.21	-10000	0	-0.48	95	95
NPHS1	-0.15	0.33	-10000	0	-0.85	73	73
Nephrin/NEPH1/podocin	-0.12	0.22	-10000	0	-0.51	95	95
TJP1	0.013	0	-10000	0	-10000	0	0
NCK1	0.013	0	-10000	0	-10000	0	0
NCK2	0.013	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.13	0.24	-10000	0	-0.54	95	95
CD2AP	0.013	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.13	0.24	-10000	0	-0.54	95	95
GRB2	0.013	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.11	0.24	-10000	0	-0.52	97	97
cytoskeleton organization	-0.096	0.25	-10000	0	-0.53	95	95
Nephrin/NEPH1	-0.12	0.23	-10000	0	-0.53	95	95
Nephrin/NEPH1/ZO-1	-0.14	0.25	-10000	0	-0.58	95	95

×

Endothelins

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
AKT1	-0.057	0.15	-9999	-0.58	9	9
PTK2B	0.013	0.001	-9999	-10000	0	0
mol:Ca2+	-0.13	0.28	-9999	-0.68	51	51
EDN1	-0.049	0.13	-9999	-0.77	7	7
EDN3	-0.42	0.43	-9999	-0.85	207	207
EDN2	-0.012	0.11	-9999	-0.4	25	25
HRAS/GDP	-0.1	0.24	-9999	-0.51	77	77
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.084	0.18	-9999	-0.38	85	85
ADCY4	-0.1	0.2	-9999	-0.53	55	55
ADCY5	-0.17	0.26	-9999	-0.59	96	96
ADCY6	-0.1	0.2	-9999	-0.53	55	55
ADCY7	-0.1	0.2	-9999	-0.53	55	55
ADCY1	-0.11	0.21	-9999	-0.56	56	56
ADCY2	-0.15	0.25	-9999	-0.59	82	82
ADCY3	-0.1	0.2	-9999	-0.53	55	55
ADCY8	-0.21	0.21	-9999	-0.56	79	79
ADCY9	-0.1	0.2	-9999	-0.53	55	55
arachidonic acid secretion	-0.18	0.32	-9999	-0.62	120	120
ETB receptor/Endothelin-1/Gq/GTP	-0.093	0.21	-9999	-0.44	95	95
GNAO1	-0.015	0.15	-9999	-0.72	16	16
HRAS	0.009	0.023	-9999	-0.31	2	2
ETA receptor/Endothelin-1/G12/GTP	-0.021	0.16	-9999	-0.54	9	9
ETA receptor/Endothelin-1/Gs/GTP	-0.086	0.23	-9999	-0.56	56	56
mol:GTP	-0.003	0.009	-9999	-10000	0	0
COL3A1	-0.075	0.18	-9999	-0.52	32	32
EDNRB	0.002	0.088	-9999	-0.85	4	4
response to oxidative stress	0	0	-9999	-10000	0	0
CYSLTR2	-0.17	0.24	-9999	-0.64	49	49
CYSLTR1	-0.063	0.17	-9999	-0.74	11	11
SLC9A1	-0.024	0.077	-9999	-0.31	7	7
mol:GDP	-0.12	0.25	-9999	-0.54	80	80
SLC9A3	-0.051	0.19	-9999	-0.78	19	19
RAF1	-0.15	0.29	-9999	-0.56	114	114
JUN	-0.28	0.52	-9999	-1.2	97	97
JAK2	-0.057	0.15	-9999	-0.58	9	9
mol:IP3	-0.11	0.22	-9999	-0.49	89	89
ETA receptor/Endothelin-1	-0.041	0.2	-9999	-0.48	33	33
PLCB1	0.006	0.061	-9999	-0.85	2	2
PLCB2	0.005	0.043	-9999	-0.32	4	4
ETA receptor/Endothelin-3	-0.35	0.34	-9999	-0.69	206	206
FOS	-0.26	0.48	-9999	-1	108	108
Gai/GDP	-0.001	0.12	-9999	-0.65	12	12
CRK	0.013	0.001	-9999	-10000	0	0
mol:Ca ++	-0.12	0.23	-9999	-0.54	66	66
BCAR1	0.013	0.002	-9999	-10000	0	0
PRKCB1	-0.11	0.22	-9999	-0.48	90	90
GNAQ	0.011	0.008	-9999	-10000	0	0
GNAZ	0.013	0	-9999	-10000	0	0
GNAL	-0.09	0.28	-9999	-0.85	49	49
Gs family/GDP	-0.19	0.25	-9999	-0.56	107	107
ETA receptor/Endothelin-1/Gq/GTP	-0.11	0.21	-9999	-0.45	90	90
MAPK14	-0.061	0.17	-9999	-0.38	61	61
TRPC6	-0.14	0.29	-9999	-0.74	48	48
GNAI2	0.013	0	-9999	-10000	0	0
GNAI3	0.013	0	-9999	-10000	0	0
GNAI1	0.013	0	-9999	-10000	0	0
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.073	0.18	-9999	-0.37	87	87
ETB receptor/Endothelin-2	-0.024	0.1	-9999	-0.63	9	9
ETB receptor/Endothelin-3	-0.34	0.33	-9999	-0.66	207	207
ETB receptor/Endothelin-1	-0.023	0.12	-9999	-0.62	11	11
MAPK3	-0.23	0.43	-9999	-0.89	113	113
MAPK1	-0.23	0.43	-9999	-0.89	113	113
Rac1/GDP	-0.1	0.23	-9999	-0.52	73	73
cAMP biosynthetic process	-0.14	0.22	-9999	-0.58	62	62
MAPK8	-0.16	0.32	-9999	-0.6	113	113
SRC	0.012	0.016	-9999	-0.32	1	1
ETB receptor/Endothelin-1/Gi/GTP	0.009	0.074	-9999	-0.32	9	9
p130Cas/CRK/Src/PYK2	-0.13	0.29	-9999	-0.56	100	100
mol:K +	0	0	-9999	-10000	0	0
G12/GDP	-0.1	0.23	-9999	-0.52	73	73
COL1A2	-0.042	0.16	-9999	-0.58	10	10
EntrezGene:2778	0	0	-9999	-10000	0	0
ETA receptor/Endothelin-2	-0.029	0.1	-9999	-0.52	9	9
mol:DAG	-0.11	0.23	-9999	-0.49	89	89
MAP2K2	-0.18	0.35	-9999	-0.68	116	116
MAP2K1	-0.18	0.35	-9999	-0.68	115	115
EDNRA	-0.041	0.099	-9999	-0.53	4	4
positive regulation of muscle contraction	-0.041	0.13	-9999	-0.55	7	7
Gq family/GDP	-0.19	0.29	-9999	-0.67	98	98
HRAS/GTP	-0.13	0.26	-9999	-0.54	91	91
PRKCH	-0.1	0.22	-9999	-0.48	87	87
RAC1	0.013	0	-9999	-10000	0	0
PRKCA	-0.13	0.26	-9999	-0.55	91	91
PRKCB	-0.12	0.22	-9999	-0.49	83	83
PRKCE	-0.1	0.23	-9999	-0.51	78	78
PRKCD	-0.1	0.22	-9999	-0.5	77	77
PRKCG	-0.11	0.22	-9999	-0.49	83	83
regulation of vascular smooth muscle contraction	-0.3	0.55	-9999	-1.2	108	108
PRKCQ	-0.11	0.23	-9999	-0.51	81	81
PLA2G4A	-0.2	0.36	-9999	-0.69	120	120
GNA14	-0.18	0.36	-9999	-0.86	92	92
GNA15	-0.015	0.093	-9999	-0.33	30	30
GNA12	0.013	0	-9999	-10000	0	0
GNA11	0.002	0.085	-9999	-0.85	4	4
Rac1/GTP	-0.021	0.16	-9999	-0.54	9	9
MMP1	-0.099	0.16	-9999	-10000	0	0

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.002	0.029	-10000	0	-0.57	1	1
fibroblast growth factor receptor signaling pathway	-0.002	0.029	-10000	0	-0.57	1	1
LAMA1	-0.053	0.23	-10000	0	-0.83	32	32
PRNP	0.013	0	-10000	0	-10000	0	0
GPC1/SLIT2	-0.096	0.23	-10000	0	-0.66	59	59
SMAD2	0.029	0.04	-10000	0	-0.52	1	1
GPC1/PrPc/Cu2+	0	0.008	-10000	0	-10000	0	0
GPC1/Laminin alpha1	-0.051	0.17	-10000	0	-0.66	31	31
TDGF1	-0.35	0.42	-10000	0	-0.85	170	170
CRIPTO/GPC1	-0.27	0.32	-10000	0	-0.66	170	170
APP/GPC1	0	0.01	-10000	0	-10000	0	0
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.22	0.29	-10000	0	-0.57	170	170
FLT1	0.013	0	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	-0.006	0.039	-10000	0	-0.57	1	1
SERPINC1	0.011	0.016	-10000	0	-10000	0	0
FYN	-0.22	0.29	-10000	0	-0.57	170	170
FGR	-0.22	0.29	-10000	0	-0.57	170	170
positive regulation of MAPKKK cascade	-0.28	0.32	-10000	0	-0.64	172	172
SLIT2	-0.11	0.3	-10000	0	-0.84	60	60
GPC1/NRG	-0.066	0.2	-10000	0	-0.66	40	40
NRG1	-0.073	0.26	-10000	0	-0.82	42	42
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.003	0.04	-10000	0	-0.57	2	2
LYN	-0.22	0.29	-10000	0	-0.57	170	170
mol:Spermine	0.012	0.011	-10000	0	-10000	0	0
cell growth	-0.002	0.029	-10000	0	-0.57	1	1
BMP signaling pathway	-0.012	0.016	0.31	1	-10000	0	1
SRC	-0.22	0.29	-10000	0	-0.57	170	170
TGFBR1	0.004	0.055	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.27	0.38	-10000	0	-0.72	158	158
GPC1	0.012	0.016	-10000	0	-0.31	1	1
TGFBR1 (dimer)	0.004	0.055	-10000	0	-10000	0	0
VEGFA	0.009	0.06	-10000	0	-0.85	2	2
BLK	-0.4	0.39	-10000	0	-0.7	234	234
HCK	-0.23	0.29	-10000	0	-0.57	170	170
FGF2	0.013	0	-10000	0	-10000	0	0
FGFR1	0.011	0.043	-10000	0	-0.85	1	1
VEGFR1 homodimer	0.013	0	-10000	0	-10000	0	0
TGFBR2	0.011	0.043	-10000	0	-0.85	1	1
cell death	0	0.01	-10000	0	-10000	0	0
ATIII/GPC1	-0.001	0.014	-10000	0	-10000	0	0
PLA2G2A/GPC1	-0.21	0.29	-10000	0	-0.66	118	118
LCK	-0.23	0.29	-10000	0	-0.57	175	175
neuron differentiation	-0.066	0.2	-10000	0	-0.66	40	40
PrPc/Cu2+	0	0	-10000	0	-10000	0	0
APP	0.013	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.011	0.043	-10000	0	-0.85	1	1

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.013	0	-10000	0	-10000	0	0
EPHB2	0.006	0.074	-10000	0	-0.85	3	3
EFNB1	-0.009	0.14	-10000	0	-0.66	18	18
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.26	0.26	-10000	0	-0.55	170	170
Ephrin B2/EPHB1-2	-0.2	0.26	-10000	0	-0.53	156	156
neuron projection morphogenesis	-0.24	0.24	-10000	0	-0.52	170	170
Ephrin B1/EPHB1-2/Tiam1	-0.28	0.28	-10000	0	-0.59	170	170
DNM1	-0.027	0.18	-10000	0	-0.82	19	19
cell-cell signaling	-0.001	0.002	-10000	0	-10000	0	0
MAP2K4	0.011	0.056	-10000	0	-0.76	2	2
YES1	-0.003	0.07	-10000	0	-1	2	2
Ephrin B1/EPHB1-2/NCK2	-0.2	0.26	-10000	0	-0.5	170	170
PI3K	0.01	0.074	-10000	0	-1	2	2
mol:GDP	-0.28	0.27	-10000	0	-0.58	170	170
ITGA2B	-0.088	0.28	-10000	0	-0.85	48	48
endothelial cell proliferation	0	0	-10000	0	-10000	0	0
FYN	-0.003	0.07	-10000	0	-1	2	2
MAP3K7	-0.006	0.057	-10000	0	-0.81	2	2
FGR	-0.005	0.07	-10000	0	-1	2	2
TIAM1	-0.17	0.16	-10000	0	-0.32	230	230
PIK3R1	0.013	0	-10000	0	-10000	0	0
RGS3	0.013	0	-10000	0	-10000	0	0
cell adhesion	-0.047	0.21	-10000	0	-0.54	55	55
LYN	-0.003	0.07	-10000	0	-1	2	2
Ephrin B1/EPHB1-2/Src Family Kinases	-0.007	0.065	-10000	0	-0.94	2	2
Ephrin B1/EPHB1-2	-0.014	0.061	-10000	0	-0.87	2	2
SRC	-0.005	0.07	-10000	0	-1	2	2
ITGB3	-0.014	0.15	-10000	0	-0.85	13	13
EPHB1	-0.31	0.42	-10000	0	-0.85	154	154
EPHB4	0.013	0	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0	0	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.096	0.25	-10000	0	-0.72	55	55
BLK	-0.061	0.11	-10000	0	-1	2	2
HCK	-0.006	0.07	-10000	0	-1	2	2
regulation of stress fiber formation	0.2	0.25	0.49	170	-10000	0	170
MAPK8	0.015	0.087	-10000	0	-0.93	3	3
Ephrin B1/EPHB1-2/RGS3	-0.2	0.26	-10000	0	-0.5	170	170
endothelial cell migration	-0.001	0.05	-10000	0	-0.71	2	2
NCK2	0.013	0	-10000	0	-10000	0	0
PTPN13	0.012	0.069	-10000	0	-0.96	2	2
regulation of focal adhesion formation	0.2	0.25	0.49	170	-10000	0	170
chemotaxis	0.2	0.25	0.49	170	-10000	0	170
PIK3CA	0.011	0.043	-10000	0	-0.85	1	1
Rac1/GTP	-0.25	0.25	-10000	0	-0.54	170	170
angiogenesis	-0.014	0.061	-10000	0	-0.87	2	2
LCK	-0.008	0.073	-10000	0	-1	2	2

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.047	0.096	-10000	0	-10000	0	0
SMARCC2	0.014	0.012	-10000	0	-10000	0	0
SMARCC1	0.014	0.012	-10000	0	-10000	0	0
TBX21	-0.16	0.29	-10000	0	-0.61	80	80
SUMO2	0.014	0.013	-10000	0	-10000	0	0
STAT1 (dimer)	0.015	0.05	-10000	0	-0.32	9	9
FKBP4	0.013	0	-10000	0	-10000	0	0
FKBP5	0.003	0.095	-10000	0	-0.85	5	5
GR alpha/HSP90/FKBP51/HSP90	0.13	0.13	0.35	36	-0.54	5	41
PRL	-0.092	0.12	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/TIF2	0.27	0.31	0.58	140	-0.54	16	156
RELA	-0.038	0.09	-10000	0	-10000	0	0
FGG	0.25	0.19	0.52	93	-10000	0	93
GR beta/TIF2	0.098	0.23	0.36	56	-0.6	30	86
IFNG	-0.51	0.52	-10000	0	-1.1	141	141
apoptosis	0.035	0.24	0.49	58	-0.54	1	59
CREB1	0.011	0.022	-10000	0	-10000	0	0
histone acetylation	-0.075	0.16	-10000	0	-0.4	52	52
BGLAP	-0.1	0.15	-10000	0	-0.56	4	4
GR/PKAc	0.14	0.1	0.35	27	-10000	0	27
NF kappa B1 p50/RelA	-0.075	0.16	-10000	0	-0.44	26	26
SMARCD1	0.014	0.012	-10000	0	-10000	0	0
MDM2	0.12	0.096	0.28	80	-10000	0	80
GATA3	-0.032	0.2	-10000	0	-0.83	24	24
AKT1	0	0	-10000	0	-10000	0	0
CSF2	-0.21	0.16	-10000	0	-0.62	21	21
GSK3B	0.014	0.013	-10000	0	-10000	0	0
NR1I3	0.061	0.24	0.51	39	-0.78	4	43
CSN2	0.21	0.14	0.44	56	-10000	0	56
BRG1/BAF155/BAF170/BAF60A	0.008	0.04	-10000	0	-10000	0	0
NFATC1	0.002	0.1	-10000	0	-0.85	6	6
POU2F1	0.013	0.016	-10000	0	-0.3	1	1
CDKN1A	0.022	0.057	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.001	0.013	-10000	0	-10000	0	0
SFN	-0.21	0.19	-10000	0	-0.34	265	265
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.047	0.17	0.35	12	-0.47	15	27
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.079	0.45	0.49	40	-0.9	89	129
JUN	-0.34	0.3	-10000	0	-0.7	143	143
IL4	-0.13	0.17	-10000	0	-0.61	23	23
CDK5R1	0.011	0.024	-10000	0	-0.32	2	2
PRKACA	0.013	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.37	0.43	-10000	0	-0.86	150	150
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.13	0.13	0.35	33	-0.49	5	38
cortisol/GR alpha (monomer)	0.38	0.31	0.68	164	-10000	0	164
NCOA2	-0.05	0.22	-10000	0	-0.85	30	30
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.26	0.37	-10000	0	-0.88	106	106
AP-1/NFAT1-c-4	-0.57	0.5	-10000	0	-0.99	198	198
AFP	-0.23	0.21	-10000	0	-0.63	53	53
SUV420H1	0.013	0	-10000	0	-10000	0	0
IRF1	0.2	0.15	0.52	31	-10000	0	31
TP53	0.032	0.023	-10000	0	-10000	0	0
PPP5C	0.013	0	-10000	0	-10000	0	0
KRT17	-0.48	0.38	-10000	0	-0.82	165	165
KRT14	-0.24	0.18	-10000	0	-0.56	35	35
TBP	0.022	0.009	-10000	0	-10000	0	0
CREBBP	0.064	0.063	-10000	0	-10000	0	0
HDAC1	0.01	0.005	-10000	0	-10000	0	0
HDAC2	0.03	0.014	-10000	0	-10000	0	0
AP-1	-0.58	0.5	-10000	0	-0.99	200	200
MAPK14	0.014	0.012	-10000	0	-10000	0	0
MAPK10	0.014	0.013	-10000	0	-10000	0	0
MAPK11	0.014	0.013	-10000	0	-10000	0	0
KRT5	-0.56	0.55	-10000	0	-1.1	161	161
interleukin-1 receptor activity	0.017	0.013	-10000	0	-10000	0	0
NCOA1	0.017	0.001	-10000	0	-10000	0	0
STAT1	0.015	0.05	-10000	0	-0.32	9	9
CGA	-0.13	0.16	-10000	0	-0.56	17	17
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.24	0.14	0.38	155	-10000	0	155
MAPK3	0.014	0.013	-10000	0	-10000	0	0
MAPK1	0.014	0.012	-10000	0	-10000	0	0
ICAM1	-0.27	0.27	-10000	0	-0.68	89	89
NFKB1	-0.038	0.09	-10000	0	-10000	0	0
MAPK8	-0.19	0.19	-10000	0	-0.48	86	86
MAPK9	0.014	0.012	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.03	0.25	0.5	57	-0.56	1	58
BAX	0.028	0.031	-10000	0	-10000	0	0
POMC	-0.56	0.7	-10000	0	-1.4	134	134
EP300	0.064	0.064	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/p53	0.34	0.24	0.59	156	-10000	0	156
proteasomal ubiquitin-dependent protein catabolic process	0.089	0.073	0.25	25	-10000	0	25
SGK1	0.11	0.21	-10000	0	-1.4	7	7
IL13	-0.31	0.26	-10000	0	-0.81	55	55
IL6	-0.43	0.56	-10000	0	-1.3	109	109
PRKACG	0.002	0.005	-10000	0	-10000	0	0
IL5	-0.27	0.21	-10000	0	-0.71	43	43
IL2	-0.37	0.27	-10000	0	-0.73	105	105
CDK5	0.012	0.008	-10000	0	-10000	0	0
PRKACB	0.013	0	-10000	0	-10000	0	0
HSP90AA1	0.013	0	-10000	0	-10000	0	0
IL8	-0.28	0.32	-10000	0	-0.77	78	78
CDK5R1/CDK5	0.007	0.024	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	-0.033	0.12	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.31	0.22	0.56	146	-10000	0	146
SMARCA4	0.014	0.012	-10000	0	-10000	0	0
chromatin remodeling	0.21	0.15	0.4	106	-0.36	2	108
NF kappa B1 p50/RelA/Cbp	0.017	0.16	-10000	0	-0.49	3	3
JUN (dimer)	-0.34	0.3	-10000	0	-0.69	143	143
YWHAH	0.013	0	-10000	0	-10000	0	0
VIPR1	-0.25	0.43	-10000	0	-1	85	85
NR3C1	0.22	0.2	0.5	106	-10000	0	106
NR4A1	-0.32	0.42	-10000	0	-0.76	179	179
TIF2/SUV420H1	-0.048	0.17	-10000	0	-0.66	30	30
MAPKKK cascade	0.035	0.24	0.49	58	-0.54	1	59
cortisol/GR alpha (dimer)/Src-1	0.33	0.24	0.58	158	-10000	0	158
PBX1	0.012	0.043	-10000	0	-0.85	1	1
POU1F1	0.006	0.008	-10000	0	-10000	0	0
SELE	-0.35	0.5	-10000	0	-1.2	88	88
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.21	0.15	0.4	106	-0.36	2	108
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.31	0.22	0.56	146	-10000	0	146
mol:cortisol	0.22	0.2	0.4	167	-10000	0	167
MMP1	-0.22	0.15	-10000	0	-0.44	50	50

×

Glypican 2 network

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
MDK	-0.087	0.15	-9999	-0.32	124	124
GPC2	-0.018	0.096	-9999	-0.31	39	39
GPC2/Midkine	-0.081	0.12	-9999	-0.41	17	17
neuron projection morphogenesis	-0.081	0.12	-9999	-0.41	17	17

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.23	0.55	-9999	-1.2	73	73
IL23A	-0.24	0.56	-9999	-1.3	74	74
NF kappa B1 p50/RelA/I kappa B alpha	-0.3	0.47	-9999	-1.2	76	76
positive regulation of T cell mediated cytotoxicity	-0.26	0.62	-9999	-1.3	85	85
ITGA3	-0.21	0.51	-9999	-1.2	69	69
IL17F	-0.11	0.34	-9999	-0.73	66	66
IL12B	-0.003	0.1	-9999	-0.55	10	10
STAT1 (dimer)	-0.25	0.58	-9999	-1.2	83	83
CD4	-0.2	0.5	-9999	-1.1	74	74
IL23	-0.24	0.53	-9999	-1.2	74	74
IL23R	-0.006	0.098	-9999	-10000	0	0
IL1B	-0.25	0.59	-9999	-1.4	69	69
T-helper cell lineage commitment	0	0	-9999	-10000	0	0
IL24	-0.21	0.5	-9999	-1.1	77	77
TYK2	0.013	0.022	-9999	-10000	0	0
STAT4	-0.031	0.15	-9999	-0.45	39	39
STAT3	0.013	0	-9999	-10000	0	0
IL18RAP	-0.03	0.18	-9999	-0.82	20	20
IL12RB1	-0.022	0.12	-9999	-0.38	35	35
PIK3CA	0.011	0.043	-9999	-0.85	1	1
IL12Rbeta1/TYK2	-0.01	0.092	-9999	-0.7	3	3
IL23R/JAK2	-0.003	0.12	-9999	-10000	0	0
positive regulation of chronic inflammatory response	-0.26	0.62	-9999	-1.3	85	85
natural killer cell activation	0.002	0.009	-9999	-10000	0	0
JAK2	0.021	0.026	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
NFKB1	0.013	0.004	-9999	-10000	0	0
RELA	0.013	0.004	-9999	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.22	0.5	-9999	-1.1	74	74
ALOX12B	-0.22	0.51	-9999	-1.2	71	71
CXCL1	-0.23	0.53	-9999	-1.2	78	78
T cell proliferation	-0.26	0.62	-9999	-1.3	85	85
NFKBIA	0.013	0.004	-9999	-10000	0	0
IL17A	-0.067	0.28	-9999	-0.57	54	54
PI3K	-0.31	0.48	-9999	-1.2	80	80
IFNG	-0.021	0.055	-9999	-0.13	69	69
STAT3 (dimer)	-0.29	0.45	-9999	-1.1	77	77
IL18R1	-0.032	0.15	-9999	-0.42	41	41
IL23/IL23R/JAK2/TYK2/SOCS3	-0.11	0.33	-9999	-0.74	52	52
IL18/IL18R	-0.074	0.19	-9999	-0.6	38	38
macrophage activation	-0.015	0.018	-9999	-0.044	76	76
TNF	-0.28	0.62	-9999	-1.4	86	86
STAT3/STAT4	-0.32	0.49	-9999	-1.2	85	85
STAT4 (dimer)	-0.26	0.59	-9999	-1.3	82	82
IL18	-0.041	0.16	-9999	-0.42	50	50
IL19	-0.21	0.5	-9999	-1.1	75	75
STAT5A (dimer)	-0.24	0.58	-9999	-1.3	79	79
STAT1	0.006	0.048	-9999	-0.31	9	9
SOCS3	-0.054	0.23	-9999	-0.85	32	32
CXCL9	-0.3	0.63	-9999	-1.3	95	95
MPO	-0.21	0.52	-9999	-1.1	79	79
positive regulation of humoral immune response	-0.26	0.62	-9999	-1.3	85	85
IL23/IL23R/JAK2/TYK2	-0.31	0.75	-9999	-1.5	85	85
IL6	-0.35	0.67	-9999	-1.4	108	108
STAT5A	0.013	0	-9999	-10000	0	0
IL2	0.001	0.017	-9999	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0.002	0.009	-9999	-10000	0	0
CD3E	-0.24	0.58	-9999	-1.3	78	78
keratinocyte proliferation	-0.26	0.62	-9999	-1.3	85	85
NOS2	-0.22	0.51	-9999	-1.1	78	78

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.12	0.23	-10000	0	-0.62	65	65
FYN	-0.11	0.35	-10000	0	-0.79	74	74
LAT/GRAP2/SLP76	-0.13	0.28	-10000	0	-0.66	78	78
IKBKB	0.013	0	-10000	0	-10000	0	0
AKT1	-0.055	0.22	-10000	0	-0.47	77	77
B2M	0.012	0.006	-10000	0	-10000	0	0
IKBKG	-0.031	0.05	-10000	0	-0.19	9	9
MAP3K8	0	0.1	-10000	0	-0.85	6	6
mol:Ca2+	-0.032	0.051	-10000	0	-0.13	86	86
integrin-mediated signaling pathway	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.11	0.33	-10000	0	-0.72	79	79
TRPV6	-0.18	0.35	-10000	0	-0.86	84	84
CD28	-0.048	0.2	-10000	0	-0.61	40	40
SHC1	-0.12	0.35	-10000	0	-0.8	73	73
receptor internalization	-0.14	0.39	-10000	0	-0.83	81	81
PRF1	-0.12	0.35	-10000	0	-0.85	64	64
KRAS	0.013	0	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
COT/AKT1	-0.038	0.18	-10000	0	-0.38	76	76
LAT	-0.12	0.35	-10000	0	-0.82	73	73
EntrezGene:6955	0	0.003	-10000	0	-10000	0	0
CD3D	-0.097	0.28	-10000	0	-0.74	60	60
CD3E	-0.074	0.26	-10000	0	-0.77	46	46
CD3G	-0.15	0.33	-10000	0	-0.81	80	80
RASGRP2	0	0.03	-10000	0	-0.19	4	4
RASGRP1	-0.052	0.22	-10000	0	-0.47	78	78
HLA-A	0.011	0.017	-10000	0	-10000	0	0
RASSF5	0.013	0	-10000	0	-10000	0	0
RAP1A/GTP/RAPL	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.01	0.068	-10000	0	-0.12	53	53
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.057	0.09	-10000	0	-0.25	54	54
PRKCA	-0.066	0.14	-10000	0	-0.32	79	79
GRAP2	-0.046	0.22	-10000	0	-0.8	30	30
mol:IP3	-0.053	0.24	0.28	71	-0.47	74	145
EntrezGene:6957	0	0.004	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.16	0.43	-10000	0	-0.96	72	72
ORAI1	0.088	0.16	0.4	84	-10000	0	84
CSK	-0.12	0.36	-10000	0	-0.82	73	73
B7 family/CD28	-0.2	0.36	-10000	0	-0.76	97	97
CHUK	0.013	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.16	0.43	-10000	0	-0.94	80	80
PTPN6	-0.13	0.36	-10000	0	-0.83	73	73
VAV1	-0.13	0.35	-10000	0	-0.79	77	77
Monovalent TCR/CD3	-0.17	0.43	-10000	0	-0.76	101	101
CBL	0.013	0	-10000	0	-10000	0	0
LCK	-0.12	0.37	-10000	0	-0.85	72	72
PAG1	-0.12	0.36	-10000	0	-0.82	73	73
RAP1A	0.013	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.16	0.43	-10000	0	-0.95	78	78
CD80	-0.086	0.27	-10000	0	-0.83	48	48
CD86	-0.011	0.11	-10000	0	-0.41	23	23
PDK1/CARD11/BCL10/MALT1	-0.07	0.11	-10000	0	-0.3	60	60
HRAS	0.012	0.023	-10000	0	-0.31	2	2
GO:0035030	-0.11	0.3	-10000	0	-0.6	97	97
CD8A	-0.049	0.22	-10000	0	-0.86	29	29
CD8B	-0.096	0.28	-10000	0	-0.75	59	59
PTPRC	-0.036	0.18	-10000	0	-0.6	32	32
PDK1/PKC theta	-0.071	0.27	-10000	0	-0.58	78	78
CSK/PAG1	-0.11	0.35	-10000	0	-0.83	67	67
SOS1	0.013	0	-10000	0	-10000	0	0
peptide-MHC class I	0.014	0.016	-10000	0	-10000	0	0
GRAP2/SLP76	-0.16	0.33	-10000	0	-0.78	78	78
STIM1	0.047	0.083	-10000	0	-10000	0	0
RAS family/GTP	0.008	0.092	-10000	0	-0.18	48	48
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.16	0.44	-10000	0	-0.94	81	81
mol:DAG	-0.072	0.18	-10000	0	-0.41	78	78
RAP1A/GDP	0.006	0.03	-10000	0	-10000	0	0
PLCG1	0.013	0	-10000	0	-10000	0	0
CD247	-0.029	0.18	-10000	0	-0.65	26	26
cytotoxic T cell degranulation	-0.11	0.33	-10000	0	-0.78	67	67
RAP1A/GTP	-0.003	0.009	-10000	0	-0.07	3	3
mol:PI-3-4-5-P3	-0.076	0.26	-10000	0	-0.57	79	79
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.083	0.3	0.3	65	-0.62	77	142
NRAS	0.013	0	-10000	0	-10000	0	0
ZAP70	-0.025	0.17	-10000	0	-0.67	23	23
GRB2/SOS1	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.12	0.26	-10000	0	-0.62	78	78
MALT1	0.013	0	-10000	0	-10000	0	0
TRAF6	0.011	0.043	-10000	0	-0.85	1	1
CD8 heterodimer	-0.11	0.3	-10000	0	-0.78	62	62
CARD11	-0.076	0.17	-10000	0	-0.36	98	98
PRKCB	-0.059	0.13	-10000	0	-0.31	69	69
PRKCE	-0.052	0.12	-10000	0	-0.3	61	61
PRKCQ	-0.095	0.31	-10000	0	-0.68	79	79
LCP2	0.007	0.045	-10000	0	-0.31	8	8
BCL10	0.013	0	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.041	0.19	-10000	0	-0.4	77	77
IKK complex	0.012	0.07	-10000	0	-0.12	44	44
RAS family/GDP	-0.005	0.01	-10000	0	-10000	0	0
MAP3K14	-0.017	0.14	-10000	0	-0.3	58	58
PDPK1	-0.048	0.21	-10000	0	-0.44	78	78
TCR/CD3/MHC I/CD8/Fyn	-0.17	0.46	-10000	0	-1.1	73	73

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.013	0	-10000	0	-10000	0	0
PTK2	0.013	0	-10000	0	-10000	0	0
CRKL	-0.12	0.24	-10000	0	-0.48	122	122
GRB2/SOS1/SHC	0	0	-10000	0	-10000	0	0
HRAS	0.012	0.023	-10000	0	-0.31	2	2
IRS1/Crk	-0.12	0.24	-10000	0	-0.48	122	122
IGF-1R heterotetramer/IGF1/PTP1B	-0.13	0.23	-10000	0	-0.55	89	89
AKT1	-0.086	0.22	-10000	0	-0.8	11	11
BAD	-0.072	0.2	-10000	0	-0.72	11	11
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.12	0.24	-10000	0	-0.48	122	122
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.14	0.23	-10000	0	-0.48	122	122
RAF1	-0.063	0.19	-10000	0	-0.67	11	11
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.14	0.22	-10000	0	-0.45	122	122
YWHAZ	0.013	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.16	0.25	-10000	0	-0.52	122	122
PIK3CA	0.011	0.043	-10000	0	-0.85	1	1
RPS6KB1	-0.086	0.22	-10000	0	-0.8	11	11
GNB2L1	0.013	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.054	0.17	-10000	0	-0.54	11	11
PXN	0.013	0	-10000	0	-10000	0	0
PIK3R1	0.013	0	-10000	0	-10000	0	0
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
HRAS/GTP	-0.12	0.19	-10000	0	-0.76	11	11
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.1	0.18	-10000	0	-0.44	89	89
IGF-1R heterotetramer	-0.018	0.048	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.14	0.23	-10000	0	-0.48	122	122
Crk/p130 Cas/Paxillin	-0.13	0.21	-10000	0	-0.46	89	89
IGF1R	-0.018	0.048	-10000	0	-10000	0	0
IGF1	-0.19	0.36	-10000	0	-0.84	94	94
IRS2/Crk	-0.11	0.23	-10000	0	-0.48	89	89
PI3K	-0.14	0.22	-10000	0	-0.45	122	122
apoptosis	0.054	0.18	0.59	11	-10000	0	11
HRAS/GDP	-0.001	0.015	-10000	0	-10000	0	0
PRKCD	-0.1	0.25	-10000	0	-0.55	89	89
RAF1/14-3-3 E	-0.046	0.17	-10000	0	-0.55	11	11
BAD/14-3-3	-0.058	0.19	-10000	0	-0.64	11	11
PRKCZ	-0.086	0.22	-10000	0	-0.8	11	11
Crk/p130 Cas/Paxillin/FAK1	-0.099	0.16	-10000	0	-0.66	11	11
PTPN1	0.013	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.12	0.26	-10000	0	-0.59	89	89
BCAR1	0.013	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.11	0.2	-10000	0	-0.48	89	89
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.013	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.12	0.24	-10000	0	-0.48	122	122
GRB10	0.013	0	-10000	0	-10000	0	0
PTPN11	-0.12	0.24	-10000	0	-0.48	122	122
IRS1	-0.14	0.26	-10000	0	-0.52	122	122
IRS2	-0.12	0.24	-10000	0	-0.48	122	122
IGF-1R heterotetramer/IGF1	-0.16	0.28	-10000	0	-0.69	89	89
GRB2	0.013	0	-10000	0	-10000	0	0
PDPK1	-0.099	0.23	-10000	0	-0.46	89	89
YWHAE	0.013	0	-10000	0	-10000	0	0
PRKD1	-0.1	0.25	-10000	0	-0.55	89	89
SHC1	0.013	0	-10000	0	-10000	0	0

×

HIF-1-alpha transcription factor network

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
PKM2	-0.2	0.43	-9999	-0.98	44	44
HDAC7	0.015	0.002	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.3	0.35	-9999	-0.84	92	92
SMAD4	0.015	0.002	-9999	-10000	0	0
ID2	-0.2	0.43	-9999	-0.99	42	42
AP1	-0.3	0.47	-9999	-0.98	124	124
ABCG2	-0.2	0.43	-9999	-1	43	43
HIF1A	-0.014	0.066	-9999	-10000	0	0
TFF3	-0.6	0.53	-9999	-1.1	168	168
GATA2	0.014	0.017	-9999	-0.31	1	1
AKT1	-0.043	0.1	-9999	-10000	0	0
response to hypoxia	-0.064	0.11	-9999	-0.25	10	10
MCL1	-0.2	0.43	-9999	-0.99	42	42
NDRG1	-0.2	0.43	-9999	-0.99	42	42
SERPINE1	-0.22	0.43	-9999	-1	45	45
FECH	-0.2	0.43	-9999	-0.97	46	46
FURIN	-0.2	0.43	-9999	-0.99	42	42
NCOA2	-0.049	0.22	-9999	-0.85	30	30
EP300	-0.069	0.18	-9999	-0.34	93	93
HMOX1	-0.21	0.43	-9999	-0.99	46	46
BHLHE40	-0.21	0.43	-9999	-1	46	46
BHLHE41	-0.2	0.43	-9999	-0.97	48	48
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.017	0.036	-9999	-10000	0	0
ENG	0.041	0.091	-9999	-10000	0	0
JUN	-0.18	0.36	-9999	-0.85	93	93
RORA	-0.2	0.43	-9999	-0.99	46	46
ABCB1	-0.071	0.16	-9999	-1.5	4	4
TFRC	-0.2	0.43	-9999	-0.99	42	42
CXCR4	-0.2	0.43	-9999	-0.98	44	44
TF	-0.27	0.51	-9999	-1.1	76	76
CITED2	-0.24	0.47	-9999	-1.1	58	58
HIF1A/ARNT	-0.31	0.39	-9999	-1	61	61
LDHA	-0.041	0.05	-9999	-10000	0	0
ETS1	-0.2	0.43	-9999	-0.98	45	45
PGK1	-0.2	0.43	-9999	-0.99	43	43
NOS2	-0.22	0.44	-9999	-0.98	53	53
ITGB2	-0.21	0.43	-9999	-1	47	47
ALDOA	-0.2	0.43	-9999	-0.99	42	42
Cbp/p300/CITED2	-0.34	0.51	-9999	-1.1	91	91
FOS	-0.21	0.38	-9999	-0.85	106	106
HK2	-0.21	0.43	-9999	-1	44	44
SP1	0.022	0.006	-9999	-10000	0	0
GCK	-0.42	0.73	-9999	-1.5	118	118
HK1	-0.2	0.43	-9999	-0.99	43	43
NPM1	-0.2	0.43	-9999	-0.99	43	43
EGLN1	-0.2	0.43	-9999	-0.99	43	43
CREB1	0.022	0	-9999	-10000	0	0
PGM1	-0.2	0.43	-9999	-1	34	34
SMAD3	0.015	0.002	-9999	-10000	0	0
EDN1	-0.17	0.32	-9999	-0.76	53	53
IGFBP1	-0.22	0.43	-9999	-1	43	43
VEGFA	-0.17	0.39	-9999	-0.77	61	61
HIF1A/JAB1	-0.012	0.02	-9999	-10000	0	0
CP	-0.38	0.57	-9999	-1.1	119	119
CXCL12	-0.25	0.49	-9999	-1.1	61	61
COPS5	0.014	0.001	-9999	-10000	0	0
SMAD3/SMAD4	0	0.002	-9999	-10000	0	0
BNIP3	-0.2	0.43	-9999	-0.99	42	42
EGLN3	-0.22	0.44	-9999	-1	48	48
CA9	-0.22	0.43	-9999	-1	45	45
TERT	-0.21	0.42	-9999	-1	43	43
ENO1	-0.2	0.43	-9999	-0.99	42	42
PFKL	-0.2	0.43	-9999	-0.99	42	42
NCOA1	0.013	0	-9999	-10000	0	0
ADM	-0.24	0.45	-9999	-1	45	45
ARNT	-0.014	0.066	-9999	-10000	0	0
HNF4A	-0.027	0.065	-9999	-0.34	9	9
ADFP	-0.22	0.42	-9999	-0.93	59	59
SLC2A1	-0.17	0.38	-9999	-0.77	55	55
LEP	-0.22	0.43	-9999	-1	45	45
HIF1A/ARNT/Cbp/p300	-0.31	0.36	-9999	-0.87	93	93
EPO	-0.14	0.31	-9999	-1	11	11
CREBBP	-0.069	0.18	-9999	-0.34	93	93
HIF1A/ARNT/Cbp/p300/HDAC7	-0.29	0.34	-9999	-0.84	88	88
PFKFB3	-0.2	0.43	-9999	-1	42	42
NT5E	-0.21	0.43	-9999	-1	46	46

×

BMP receptor signaling

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
BMP7/BMPR2/BMPR1A-1B/FS	-0.29	0.34	-9999	-0.63	187	187
SMAD6-7/SMURF1	0	0	-9999	-10000	0	0
NOG	-0.06	0.23	-9999	-0.73	40	40
SMAD9	-0.22	0.29	-9999	-0.61	132	132
SMAD4	0.013	0	-9999	-10000	0	0
SMAD5	-0.1	0.21	-9999	-0.38	139	139
BMP7/USAG1	-0.34	0.33	-9999	-0.66	213	213
SMAD5/SKI	-0.09	0.2	-9999	-0.54	23	23
SMAD1	0.017	0.046	-9999	-10000	0	0
BMP2	-0.014	0.15	-9999	-0.85	13	13
SMAD1/SMAD1/SMAD4	-0.002	0.002	-9999	-10000	0	0
BMPR1A	0.013	0	-9999	-10000	0	0
BMPR1B	-0.28	0.41	-9999	-0.85	139	139
BMPR1A-1B/BAMBI	-0.2	0.28	-9999	-0.58	139	139
AHSG	-0.014	0.078	-9999	-0.31	26	26
CER1	0.001	0.003	-9999	-10000	0	0
BMP2-4/CER1	-0.037	0.14	-9999	-0.58	25	25
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.083	0.2	-9999	-0.65	27	27
BMP2-4 (homodimer)	-0.043	0.16	-9999	-0.66	25	25
RGMB	0.013	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.18	0.25	-9999	-0.52	139	139
RGMA	-0.021	0.17	-9999	-0.85	16	16
SMURF1	0.013	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.093	0.19	-9999	-0.58	25	25
BMP2-4/USAG1	-0.33	0.31	-9999	-0.6	227	227
SMAD6/SMURF1/SMAD5	-0.09	0.2	-9999	-0.54	23	23
SOSTDC1	-0.44	0.43	-9999	-0.85	214	214
BMP7/BMPR2/BMPR1A-1B	-0.18	0.25	-9999	-0.52	139	139
SKI	0.013	0	-9999	-10000	0	0
BMP6 (homodimer)	0.013	0	-9999	-10000	0	0
HFE2	0.001	0.032	-9999	-0.31	4	4
ZFYVE16	0.013	0	-9999	-10000	0	0
MAP3K7	0.013	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.048	0.16	-9999	-0.58	32	32
SMAD5/SMAD5/SMAD4	-0.09	0.2	-9999	-0.54	23	23
MAPK1	0.013	0	-9999	-10000	0	0
TAK1/TAB family	-0.098	0.14	-9999	-0.49	25	25
BMP7 (homodimer)	0.013	0	-9999	-10000	0	0
NUP214	0.013	0	-9999	-10000	0	0
BMP6/FETUA	-0.013	0.049	-9999	-10000	0	0
SMAD1/SKI	0.024	0.044	-9999	-10000	0	0
SMAD6	0.013	0	-9999	-10000	0	0
CTDSP2	0.013	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.047	0.14	-9999	-0.59	25	25
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.2	0.36	-9999	-0.74	115	115
BMPR2 (homodimer)	0.013	0	-9999	-10000	0	0
GADD34/PP1CA	-0.01	0.074	-9999	-0.57	7	7
BMPR1A-1B (homodimer)	-0.22	0.31	-9999	-0.66	139	139
CHRDL1	-0.6	0.39	-9999	-0.85	290	290
ENDOFIN/SMAD1	0.024	0.044	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.007	0.009	-9999	-10000	0	0
SMAD6/SMURF1	0.013	0	-9999	-10000	0	0
BAMBI	-0.002	0.076	-9999	-0.34	17	17
SMURF2	0.013	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.44	0.29	-9999	-0.61	295	295
BMP2-4/GREM1	-0.17	0.29	-9999	-0.64	104	104
SMAD7	0.013	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.19	0.28	-9999	-0.57	132	132
SMAD1/SMAD6	0.024	0.044	-9999	-10000	0	0
TAK1/SMAD6	0	0	-9999	-10000	0	0
BMP7	0.013	0	-9999	-10000	0	0
BMP6	0.013	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.07	0.16	-9999	-0.5	25	25
PPM1A	0.013	0	-9999	-10000	0	0
SMAD1/SMURF2	0.024	0.044	-9999	-10000	0	0
SMAD7/SMURF1	0	0	-9999	-10000	0	0
CTDSPL	0.013	0	-9999	-10000	0	0
PPP1CA	0.013	0	-9999	-10000	0	0
XIAP	0.013	0	-9999	-10000	0	0
CTDSP1	0.013	0	-9999	-10000	0	0
PPP1R15A	-0.002	0.11	-9999	-0.85	7	7
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.21	0.33	-9999	-0.82	73	73
CHRD	-0.004	0.12	-9999	-0.85	8	8
BMPR2	0.013	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.098	0.2	-9999	-0.62	25	25
BMP4	-0.016	0.15	-9999	-0.69	17	17
FST	-0.21	0.37	-9999	-0.85	103	103
BMP2-4/NOG	-0.083	0.2	-9999	-0.57	56	56
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.16	0.23	-9999	-0.48	139	139

×

Arf6 signaling events

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
CENTA1/KIF3B	0	0	-9999	-10000	0	0
ARNO/beta Arrestin1-2	-0.042	0.11	-9999	-0.51	10	10
EGFR	0.002	0.095	-9999	-0.85	5	5
EPHA2	0.011	0.028	-9999	-0.31	3	3
USP6	0.011	0.028	-9999	-10000	0	0
IQSEC1	0.013	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.099	0.23	-9999	-0.66	60	60
ARRB2	-0.043	0.15	-9999	-0.46	48	48
mol:GTP	0.021	0.011	-9999	-10000	0	0
ARRB1	0.011	0.043	-9999	-0.85	1	1
FBXO8	0.013	0	-9999	-10000	0	0
TSHR	0.009	0.06	-9999	-0.85	2	2
EGF	-0.11	0.3	-9999	-0.8	61	61
somatostatin receptor activity	0	0	-9999	-0.001	113	113
ARAP2	0.011	0.043	-9999	-0.85	1	1
mol:GDP	-0.12	0.15	-9999	-0.31	114	114
mol:PI-3-4-5-P3	0	0	-9999	-0.001	98	98
ITGA2B	-0.088	0.28	-9999	-0.85	48	48
ARF6	0.013	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.001	0.011	-9999	-10000	0	0
ADAP1	0.013	0	-9999	-10000	0	0
KIF13B	0.013	0	-9999	-10000	0	0
HGF/MET	-0.18	0.25	-9999	-0.72	62	62
PXN	0.013	0	-9999	-10000	0	0
ARF6/GTP	-0.12	0.15	-9999	-0.31	115	115
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.086	0.2	-9999	-0.57	60	60
ADRB2	-0.008	0.13	-9999	-0.85	10	10
receptor agonist activity	0	0	-9999	0	122	122
actin filament binding	0	0	-9999	-0.001	112	112
SRC	0.012	0.016	-9999	-0.31	1	1
ITGB3	-0.014	0.15	-9999	-0.85	13	13
GNAQ	0.013	0	-9999	-10000	0	0
EFA6/PI-4-5-P2	0	0.001	-9999	-0.001	108	108
ARF6/GDP	0.001	0.069	-9999	-0.37	1	1
ARF6/GDP/GULP/ACAP1	-0.19	0.2	-9999	-0.51	93	93
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.077	0.2	-9999	-0.57	55	55
ACAP1	0.001	0.078	-9999	-0.4	12	12
ACAP2	0.013	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	-0.085	0.23	-9999	-0.7	48	48
EFNA1	0.013	0	-9999	-10000	0	0
HGF	-0.12	0.31	-9999	-0.85	62	62
CYTH3	0.01	0.034	-9999	-0.67	1	1
CYTH2	0.008	0.002	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	0	108	108
endosomal lumen acidification	0	0	-9999	-0.001	121	121
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.14	0.33	-9999	-0.85	74	74
GNAQ/ARNO	0.008	0.009	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	34	34
MET	-0.12	0.16	-9999	-0.31	164	164
GNA14	-0.18	0.36	-9999	-0.85	92	92
GNA15	-0.012	0.094	-9999	-0.33	30	30
GIT1	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	114	114
GNA11	0.004	0.085	-9999	-0.85	4	4
LHCGR	-0.098	0.28	-9999	-0.79	54	54
AGTR1	-0.33	0.42	-9999	-0.85	164	164
desensitization of G-protein coupled receptor protein signaling pathway	-0.085	0.22	-9999	-0.7	48	48
IPCEF1/ARNO	-0.064	0.16	-9999	-0.45	60	60
alphaIIb/beta3 Integrin	-0.096	0.25	-9999	-0.72	55	55

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	-0.014	0.063	-10000	0	-0.37	8	8
SVIL	-0.006	0.03	-10000	0	-10000	0	0
ZNF318	0.061	0.083	0.24	1	-10000	0	1
JMJD2C	-0.064	0.069	-10000	0	-0.12	231	231
T-DHT/AR/Ubc9	-0.29	0.3	-10000	0	-0.65	170	170
CARM1	0.011	0.003	-10000	0	-10000	0	0
PRDX1	0.015	0.004	-10000	0	-10000	0	0
PELP1	0.02	0.01	-10000	0	-10000	0	0
CTNNB1	-0.002	0.023	-10000	0	-10000	0	0
AKT1	0.025	0.019	-10000	0	-10000	0	0
PTK2B	0.004	0.015	-10000	0	-10000	0	0
MED1	0.025	0.019	-10000	0	-10000	0	0
MAK	0.049	0.13	-10000	0	-0.82	5	5
response to oxidative stress	0.002	0.004	-10000	0	-10000	0	0
HIP1	-0.008	0.052	-10000	0	-0.85	1	1
GSN	-0.005	0.03	-10000	0	-10000	0	0
NCOA2	-0.052	0.22	-10000	0	-0.85	30	30
NCOA6	-0.005	0.028	-10000	0	-10000	0	0
DNA-PK	0.057	0.083	0.26	1	-10000	0	1
NCOA4	0.011	0.004	-10000	0	-10000	0	0
PIAS3	-0.002	0.023	-10000	0	-10000	0	0
cell proliferation	-0.013	0.15	-10000	0	-1.1	5	5
XRCC5	0.024	0.017	-10000	0	-10000	0	0
UBE3A	-0.015	0.046	-10000	0	-10000	0	0
T-DHT/AR/SNURF	-0.32	0.33	-10000	0	-0.68	174	174
FHL2	-0.16	0.38	-10000	0	-1.4	33	33
RANBP9	-0.005	0.028	-10000	0	-10000	0	0
JMJD1A	0.003	0.037	-10000	0	-0.12	29	29
CDK6	0.012	0.043	-10000	0	-0.85	1	1
TGFB1I1	-0.006	0.03	-10000	0	-10000	0	0
T-DHT/AR/CyclinD1	-0.3	0.31	-10000	0	-0.66	171	171
XRCC6	0.024	0.017	-10000	0	-10000	0	0
T-DHT/AR	-0.34	0.33	-10000	0	-0.66	191	191
CTDSP1	0.009	0.006	-10000	0	-10000	0	0
CTDSP2	0.045	0.05	-10000	0	-10000	0	0
BRCA1	-0.006	0.03	-10000	0	-10000	0	0
TCF4	0.035	0.034	-10000	0	-10000	0	0
CDKN2A	-0.1	0.16	-10000	0	-0.31	117	117
SRF	0.028	0.039	-10000	0	-10000	0	0
NKX3-1	-0.13	0.15	-10000	0	-0.66	10	10
KLK3	-0.43	0.71	-10000	0	-1.6	111	111
TMF1	0.009	0.006	-10000	0	-10000	0	0
HNRNPA1	0.03	0.027	-10000	0	-10000	0	0
AOF2	-0.021	0.033	-10000	0	-0.075	111	111
APPL1	0.051	0.042	-10000	0	-10000	0	0
T-DHT/AR/Caspase 8	-0.28	0.31	-10000	0	-0.64	170	170
AR	-0.39	0.43	-10000	0	-0.9	170	170
UBA3	0.009	0.006	-10000	0	-10000	0	0
PATZ1	0.03	0.027	-10000	0	-10000	0	0
PAWR	0.009	0.006	-10000	0	-10000	0	0
PRKDC	0.024	0.017	-10000	0	-10000	0	0
PA2G4	0.035	0.035	-10000	0	-10000	0	0
UBE2I	0.013	0	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.26	0.29	-10000	0	-0.6	170	170
RPS6KA3	-0.005	0.03	-10000	0	-10000	0	0
T-DHT/AR/ARA70	-0.29	0.31	-10000	0	-0.65	170	170
LATS2	0.03	0.027	-10000	0	-10000	0	0
T-DHT/AR/PRX1	-0.26	0.29	-10000	0	-0.59	170	170
Cyclin D3/CDK11 p58	0	0	-10000	0	-10000	0	0
VAV3	-0.01	0.087	-10000	0	-0.86	4	4
KLK2	-0.78	0.64	-10000	0	-1.3	231	231
CASP8	0.017	0.007	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.31	0.34	-10000	0	-0.67	176	176
TMPRSS2	-0.18	0.31	-10000	0	-1.2	28	28
CCND1	0	0.053	-10000	0	-10000	0	0
PIAS1	-0.015	0.046	-10000	0	-10000	0	0
mol:T-DHT	-0.031	0.041	-10000	0	-0.083	138	138
CDC2L1	0.001	0.002	-10000	0	-10000	0	0
PIAS4	-0.034	0.076	-10000	0	-10000	0	0
T-DHT/AR/CDK6	-0.29	0.31	-10000	0	-0.65	170	170
CMTM2	0.015	0.024	-10000	0	-0.31	2	2
SNURF	-0.023	0.17	-10000	0	-0.85	17	17
ZMIZ1	-0.011	0.037	-10000	0	-10000	0	0
CCND3	0.014	0.002	-10000	0	-10000	0	0
TGIF1	0.03	0.027	-10000	0	-10000	0	0
FKBP4	-0.005	0.028	-10000	0	-10000	0	0

×

Syndecan-1-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
TGFB1	0.008	0.039	-9999	-0.31	6	6
CCL5	-0.047	0.21	-9999	-0.75	32	32
SDCBP	0.013	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.11	0.17	-9999	-0.49	43	43
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.095	0.16	-9999	-0.69	17	17
Syndecan-1/Syntenin	-0.095	0.16	-9999	-0.69	17	17
MAPK3	-0.072	0.15	-9999	-0.63	16	16
HGF/MET	-0.18	0.25	-9999	-0.72	62	62
TGFB1/TGF beta receptor Type II	0.008	0.039	-9999	-0.31	6	6
BSG	0.012	0.016	-9999	-0.31	1	1
keratinocyte migration	-0.094	0.16	-9999	-0.67	17	17
Syndecan-1/RANTES	-0.13	0.23	-9999	-0.75	38	38
Syndecan-1/CD147	-0.094	0.15	-9999	-0.66	17	17
Syndecan-1/Syntenin/PIP2	-0.1	0.15	-9999	-0.66	17	17
LAMA5	0.013	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.1	0.14	-9999	-0.64	17	17
MMP7	-0.18	0.23	-9999	-0.37	203	203
HGF	-0.12	0.31	-9999	-0.85	62	62
Syndecan-1/CASK	-0.1	0.16	-9999	-0.47	43	43
Syndecan-1/HGF/MET	-0.22	0.24	-9999	-0.66	74	74
regulation of cell adhesion	-0.062	0.14	-9999	-0.6	16	16
HPSE	-0.022	0.15	-9999	-0.51	27	27
positive regulation of cell migration	-0.11	0.17	-9999	-0.49	43	43
SDC1	-0.11	0.17	-9999	-0.5	43	43
Syndecan-1/Collagen	-0.11	0.17	-9999	-0.49	43	43
PPIB	0.013	0	-9999	-10000	0	0
MET	-0.12	0.16	-9999	-0.31	164	164
PRKACA	0.013	0	-9999	-10000	0	0
MMP9	-0.084	0.25	-9999	-0.59	66	66
MAPK1	-0.072	0.15	-9999	-0.63	16	16
homophilic cell adhesion	-0.11	0.17	-9999	-0.49	43	43
MMP1	-0.15	0.16	-9999	-0.31	201	201

×

EPHB forward signaling

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
Ephrin A5/EPHB2	-0.1	0.22	-10000	0	-0.58	70	70
cell-cell adhesion	0.16	0.19	0.56	8	-10000	0	8
Ephrin B/EPHB2/RasGAP	-0.013	0.066	-10000	0	-0.48	7	7
ITSN1	0.013	0	-10000	0	-10000	0	0
PIK3CA	0.011	0.043	-10000	0	-0.85	1	1
SHC1	0.013	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.1	0.081	-10000	0	-10000	0	0
Ephrin B1/EPHB1	-0.22	0.28	-10000	0	-0.58	154	154
HRAS/GDP	-0.14	0.18	-10000	0	-0.41	48	48
Ephrin B/EPHB1/GRB7	-0.21	0.25	-10000	0	-0.52	157	157
Endophilin/SYNJ1	0.026	0.069	-10000	0	-0.45	7	7
KRAS	0.013	0	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.19	0.24	-10000	0	-0.5	157	157
endothelial cell migration	-0.001	0.024	-10000	0	-0.49	1	1
GRB2	0.013	0	-10000	0	-10000	0	0
GRB7	-0.037	0.12	-10000	0	-0.31	63	63
PAK1	0.034	0.071	-10000	0	-0.46	7	7
HRAS	0.012	0.023	-10000	0	-0.31	2	2
RRAS	0.026	0.071	-10000	0	-0.46	7	7
DNM1	-0.026	0.18	-10000	0	-0.82	19	19
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.16	0.25	-10000	0	-0.47	157	157
lamellipodium assembly	-0.16	0.19	-10000	0	-0.56	8	8
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.1	0.18	-10000	0	-0.34	154	154
PIK3R1	0.013	0	-10000	0	-10000	0	0
EPHB2	0.007	0.074	-10000	0	-0.85	3	3
EPHB3	-0.19	0.16	-10000	0	-0.31	254	254
EPHB1	-0.31	0.42	-10000	0	-0.85	154	154
EPHB4	0.013	0	-10000	0	-10000	0	0
mol:GDP	-0.07	0.18	-10000	0	-0.47	8	8
Ephrin B/EPHB2	-0.013	0.068	-10000	0	-0.49	7	7
Ephrin B/EPHB3	-0.086	0.082	-10000	0	-0.6	4	4
JNK cascade	-0.16	0.25	-10000	0	-0.48	156	156
Ephrin B/EPHB1	-0.2	0.24	-10000	0	-0.5	157	157
RAP1/GDP	-0.054	0.16	-10000	0	-0.5	2	2
EFNB2	0.013	0	-10000	0	-10000	0	0
EFNB3	-0.008	0.1	-10000	0	-0.42	20	20
EFNB1	0.013	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.2	0.26	-10000	0	-0.53	156	156
RAP1B	0.013	0	-10000	0	-10000	0	0
RAP1A	0.013	0	-10000	0	-10000	0	0
CDC42/GTP	-0.16	0.2	-10000	0	-0.53	13	13
Rap1/GTP	-0.16	0.19	-10000	0	-0.57	8	8
axon guidance	-0.1	0.22	-10000	0	-0.58	70	70
MAPK3	-0.078	0.17	-10000	0	-0.55	1	1
MAPK1	-0.078	0.17	-10000	0	-0.55	1	1
Rac1/GDP	-0.045	0.17	-10000	0	-0.44	6	6
actin cytoskeleton reorganization	-0.11	0.14	-10000	0	-0.45	5	5
CDC42/GDP	-0.045	0.17	-10000	0	-0.44	6	6
PI3K	-0.001	0.024	-10000	0	-0.49	1	1
EFNA5	-0.13	0.32	-10000	0	-0.84	69	69
Ephrin B2/EPHB4	0	0	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	0.029	0.052	-10000	0	-0.34	7	7
CDC42	0.013	0	-10000	0	-10000	0	0
RAS family/GTP	-0.15	0.19	-10000	0	-0.55	9	9
PTK2	0.042	0.053	-10000	0	-10000	0	0
MAP4K4	-0.16	0.26	-10000	0	-0.48	156	156
SRC	0.012	0.016	-10000	0	-0.31	1	1
KALRN	0.013	0	-10000	0	-10000	0	0
Intersectin/N-WASP	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.071	0.18	-10000	0	-0.56	2	2
MAP2K1	-0.091	0.18	-10000	0	-0.4	8	8
WASL	0.013	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.2	0.26	-10000	0	-0.52	156	156
cell migration	-0.086	0.19	-10000	0	-0.43	8	8
NRAS	0.013	0	-10000	0	-10000	0	0
SYNJ1	0.026	0.071	-10000	0	-0.46	7	7
PXN	0.013	0	-10000	0	-10000	0	0
TF	-0.036	0.19	-10000	0	-0.46	62	62
HRAS/GTP	-0.17	0.21	-10000	0	-0.42	159	159
Ephrin B1/EPHB1-2	-0.2	0.26	-10000	0	-0.53	156	156
cell adhesion mediated by integrin	0.012	0.07	0.52	4	-10000	0	4
RAC1	0.013	0	-10000	0	-10000	0	0
mol:GTP	-0.18	0.22	-10000	0	-0.46	159	159
RAC1-CDC42/GTP	-0.21	0.22	-10000	0	-0.51	119	119
RASA1	0.013	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.054	0.16	-10000	0	-0.46	3	3
ruffle organization	-0.12	0.23	-10000	0	-0.57	8	8
NCK1	0.013	0	-10000	0	-10000	0	0
receptor internalization	0.012	0.13	-10000	0	-0.48	23	23
Ephrin B/EPHB2/KALRN	-0.013	0.066	-10000	0	-0.48	7	7
ROCK1	-0.076	0.081	-10000	0	-10000	0	0
RAS family/GDP	-0.086	0.11	-10000	0	-0.54	2	2
Rac1/GTP	-0.16	0.2	-10000	0	-0.61	8	8
Ephrin B/EPHB1/Src/Paxillin	-0.11	0.19	-10000	0	-0.34	157	157

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	-0.13	0.41	-9999	-1.4	39	39
MKNK1	0.013	0	-9999	-10000	0	0
MAPK14	-0.04	0.11	-9999	-0.39	16	16
ATF2/c-Jun	-0.22	0.43	-9999	-1	93	93
MAPK11	-0.04	0.11	-9999	-0.39	16	16
MITF	-0.034	0.14	-9999	-0.4	39	39
MAPKAPK5	-0.034	0.14	-9999	-0.4	39	39
KRT8	-0.034	0.14	-9999	-0.4	39	39
MAPKAPK3	0.013	0	-9999	-10000	0	0
MAPKAPK2	0.013	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.055	0.17	-9999	-0.51	39	39
CEBPB	-0.034	0.14	-9999	-0.4	39	39
SLC9A1	-0.034	0.14	-9999	-0.4	39	39
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.07	0.18	-9999	-0.42	58	58
p38alpha-beta/MNK1	-0.031	0.14	-9999	-0.5	16	16
JUN	-0.22	0.43	-9999	-0.99	93	93
PPARGC1A	-0.24	0.25	-9999	-0.47	216	216
USF1	-0.034	0.14	-9999	-0.4	39	39
RAB5/GDP/GDI1	-0.041	0.086	-9999	-0.35	16	16
NOS2	-0.055	0.16	-9999	-0.55	16	16
DDIT3	-0.036	0.14	-9999	-0.41	39	39
RAB5A	0.013	0	-9999	-10000	0	0
HSPB1	-0.017	0.11	-9999	-0.39	16	16
p38alpha-beta/HBP1	-0.031	0.14	-9999	-0.5	16	16
CREB1	-0.049	0.16	-9999	-0.44	39	39
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	-0.019	0.12	-9999	-0.44	16	16
RPS6KA4	-0.034	0.14	-9999	-0.4	39	39
PLA2G4A	-0.061	0.22	-9999	-0.63	43	43
GDI1	-0.034	0.14	-9999	-0.4	39	39
TP53	-0.044	0.16	-9999	-0.5	39	39
RPS6KA5	-0.073	0.19	-9999	-0.46	68	68
ESR1	-0.07	0.2	-9999	-0.52	50	50
HBP1	0.013	0	-9999	-10000	0	0
MEF2C	-0.034	0.14	-9999	-0.4	39	39
MEF2A	-0.034	0.14	-9999	-0.4	39	39
EIF4EBP1	-0.05	0.16	-9999	-0.44	39	39
KRT19	-0.11	0.22	-9999	-0.56	54	54
ELK4	-0.034	0.14	-9999	-0.4	39	39
ATF6	-0.034	0.14	-9999	-0.4	39	39
ATF1	-0.049	0.16	-9999	-0.44	39	39
p38alpha-beta/MAPKAPK2	-0.031	0.14	-9999	-0.5	16	16
p38alpha-beta/MAPKAPK3	-0.031	0.14	-9999	-0.5	16	16

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.081	0.061	-9999	-10000	0	0
Syndecan-4/Syndesmos	-0.13	0.18	-9999	-0.66	34	34
positive regulation of JNK cascade	-0.17	0.2	-9999	-0.61	60	60
Syndecan-4/ADAM12	-0.17	0.18	-9999	-0.66	34	34
CCL5	-0.047	0.21	-9999	-0.75	32	32
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0.013	0	-9999	-10000	0	0
ITGA5	0.013	0	-9999	-10000	0	0
SDCBP	0.013	0	-9999	-10000	0	0
PLG	0.002	0.025	-9999	-0.31	2	2
ADAM12	-0.072	0.14	-9999	-0.31	106	106
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.066	0.046	-9999	-0.23	2	2
Syndecan-4/Laminin alpha1	-0.17	0.22	-9999	-0.7	42	42
Syndecan-4/CXCL12/CXCR4	-0.18	0.22	-9999	-0.66	55	55
Syndecan-4/Laminin alpha3	-0.15	0.19	-9999	-0.68	36	36
MDK	-0.087	0.15	-9999	-0.32	124	124
Syndecan-4/FZD7	-0.14	0.18	-9999	-0.65	36	36
Syndecan-4/Midkine	-0.18	0.19	-9999	-0.67	34	34
FZD7	0.005	0.085	-9999	-0.85	4	4
Syndecan-4/FGFR1/FGF	-0.13	0.16	-9999	-0.6	35	35
THBS1	-0.009	0.082	-9999	-0.31	28	28
integrin-mediated signaling pathway	-0.18	0.19	-9999	-0.68	34	34
positive regulation of MAPKKK cascade	-0.17	0.2	-9999	-0.61	60	60
Syndecan-4/TACI	-0.26	0.27	-9999	-0.64	114	114
CXCR4	0.011	0.028	-9999	-0.31	3	3
cell adhesion	-0.077	0.1	-9999	-0.46	24	24
Syndecan-4/Dynamin	-0.13	0.18	-9999	-0.66	34	34
Syndecan-4/TSP1	-0.14	0.18	-9999	-0.66	34	34
Syndecan-4/GIPC	-0.13	0.18	-9999	-0.66	34	34
Syndecan-4/RANTES	-0.16	0.23	-9999	-0.78	39	39
ITGB1	0.013	0	-9999	-10000	0	0
LAMA1	-0.053	0.23	-9999	-0.83	32	32
LAMA3	-0.023	0.16	-9999	-0.56	26	26
RAC1	0.013	0	-9999	-10000	0	0
PRKCA	0.003	0.2	-9999	-0.78	24	24
Syndecan-4/alpha-Actinin	-0.13	0.18	-9999	-0.66	34	34
TFPI	-0.035	0.2	-9999	-0.85	23	23
F2	-0.002	0.04	-9999	-0.33	4	4
alpha5/beta1 Integrin	0	0	-9999	-10000	0	0
positive regulation of cell adhesion	-0.18	0.22	-9999	-0.69	43	43
ACTN1	0.012	0.016	-9999	-0.31	1	1
TNC	-0.12	0.17	-9999	-0.33	161	161
Syndecan-4/CXCL12	-0.18	0.24	-9999	-0.68	60	60
FGF6	0	0.001	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
CXCL12	-0.082	0.27	-9999	-0.85	45	45
TNFRSF13B	-0.22	0.38	-9999	-0.85	105	105
FGF2	0.013	0	-9999	-10000	0	0
FGFR1	0.011	0.043	-9999	-0.85	1	1
Syndecan-4/PI-4-5-P2	-0.14	0.18	-9999	-0.66	34	34
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.22	0.15	-9999	-0.31	293	293
cell migration	-0.021	0.017	-9999	-10000	0	0
PRKCD	0.009	0.016	-9999	-10000	0	0
vasculogenesis	-0.14	0.17	-9999	-0.63	34	34
SDC4	-0.15	0.19	-9999	-0.71	34	34
Syndecan-4/Tenascin C	-0.19	0.2	-9999	-0.71	34	34
Syndecan-4/PI-4-5-P2/PKC alpha	-0.052	0.036	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.13	0.18	-9999	-0.66	34	34
MMP9	-0.086	0.24	-9999	-0.59	65	65
Rac1/GTP	-0.079	0.11	-9999	-0.47	24	24
cytoskeleton organization	-0.13	0.17	-9999	-0.63	34	34
GIPC1	0.013	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.16	0.21	-9999	-0.66	50	50

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.02	0.15	-10000	0	-0.42	23	23
TBX21	-0.12	0.44	-10000	0	-1.1	57	57
B2M	0.012	0.008	-10000	0	-10000	0	0
TYK2	0.015	0.02	-10000	0	-10000	0	0
IL12RB1	-0.019	0.12	-10000	0	-0.38	35	35
GADD45B	-0.1	0.4	-10000	0	-1	48	48
IL12RB2	-0.016	0.16	-10000	0	-0.76	17	17
GADD45G	-0.079	0.35	-10000	0	-0.9	40	40
natural killer cell activation	0.002	0.022	-10000	0	-10000	0	0
RELB	0.013	0	-10000	0	-10000	0	0
RELA	0.013	0	-10000	0	-10000	0	0
IL18	-0.037	0.16	-10000	0	-0.41	50	50
IL2RA	-0.044	0.2	-10000	0	-0.85	20	20
IFNG	-0.11	0.29	-10000	0	-0.76	65	65
STAT3 (dimer)	-0.075	0.32	-10000	0	-0.74	55	55
HLA-DRB5	-0.043	0.14	-10000	0	-0.35	62	62
FASLG	-0.15	0.49	-10000	0	-1.2	58	58
NF kappa B2 p52/RelB	-0.17	0.32	-10000	0	-0.88	55	55
CD4	0.001	0.056	-10000	0	-0.32	12	12
SOCS1	0.011	0.028	-10000	0	-0.31	3	3
EntrezGene:6955	-0.007	0.015	-10000	0	-10000	0	0
CD3D	-0.1	0.28	-10000	0	-0.74	60	60
CD3E	-0.077	0.25	-10000	0	-0.76	46	46
CD3G	-0.15	0.33	-10000	0	-0.82	80	80
IL12Rbeta2/JAK2	-0.001	0.13	-10000	0	-0.66	14	14
CCL3	-0.11	0.43	-10000	0	-1.1	43	43
CCL4	-0.16	0.52	-10000	0	-1.4	53	53
HLA-A	0.011	0.018	-10000	0	-10000	0	0
IL18/IL18R	-0.037	0.2	-10000	0	-0.59	39	39
NOS2	-0.093	0.35	-10000	0	-0.83	51	51
IL12/IL12R/TYK2/JAK2/SPHK2	-0.02	0.15	-10000	0	-0.42	22	22
IL1R1	-0.089	0.37	-10000	0	-0.98	42	42
IL4	0.001	0.028	-10000	0	-0.34	1	1
JAK2	0.015	0.02	-10000	0	-10000	0	0
EntrezGene:6957	-0.006	0.014	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.25	0.58	-10000	0	-1.2	89	89
RAB7A	-0.046	0.3	-10000	0	-0.75	28	28
lysosomal transport	-0.041	0.28	-10000	0	-0.7	31	31
FOS	-0.41	0.65	-10000	0	-1.3	133	133
STAT4 (dimer)	-0.083	0.35	-10000	0	-0.83	51	51
STAT5A (dimer)	-0.22	0.36	-10000	0	-0.87	79	79
GZMA	-0.1	0.4	-10000	0	-1	47	47
GZMB	-0.1	0.39	-10000	0	-0.99	47	47
HLX	0.004	0.053	-10000	0	-0.31	11	11
LCK	-0.11	0.42	-10000	0	-1	56	56
TCR/CD3/MHC II/CD4	-0.19	0.36	-10000	0	-0.61	118	118
IL2/IL2R	-0.08	0.23	-10000	0	-0.74	36	36
MAPK14	-0.076	0.35	-10000	0	-0.81	54	54
CCR5	-0.1	0.4	-10000	0	-1	48	48
IL1B	-0.057	0.24	-10000	0	-0.85	34	34
STAT6	-0.005	0.11	0.23	4	-0.24	29	33
STAT4	-0.031	0.15	-10000	0	-0.45	39	39
STAT3	0.013	0	-10000	0	-10000	0	0
STAT1	0.006	0.048	-10000	0	-0.31	9	9
NFKB1	0.013	0	-10000	0	-10000	0	0
NFKB2	0.013	0	-10000	0	-10000	0	0
IL12B	-0.001	0.098	-10000	0	-0.57	9	9
CD8A	-0.049	0.22	-10000	0	-0.86	29	29
CD8B	-0.097	0.28	-10000	0	-0.74	59	59
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.02	0.15	0.41	23	-10000	0	23
IL2RB	-0.015	0.14	-10000	0	-0.85	9	9
proteasomal ubiquitin-dependent protein catabolic process	-0.071	0.32	-10000	0	-0.75	51	51
IL2RG	-0.048	0.2	-10000	0	-0.85	20	20
IL12	-0.055	0.22	-10000	0	-0.67	43	43
STAT5A	0.013	0	-10000	0	-10000	0	0
CD247	-0.032	0.17	-10000	0	-0.65	26	26
IL2	0.004	0.006	-10000	0	-10000	0	0
SPHK2	0.013	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.071	0.26	-10000	0	-0.82	42	42
IL12/IL12R/TYK2/JAK2	-0.12	0.47	-10000	0	-1.1	58	58
MAP2K3	-0.078	0.35	-10000	0	-0.8	54	54
RIPK2	0.013	0	-10000	0	-10000	0	0
MAP2K6	-0.084	0.36	-10000	0	-0.82	56	56
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.031	0.14	-10000	0	-0.41	41	41
IL18RAP	-0.026	0.18	-10000	0	-0.83	20	20
IL12Rbeta1/TYK2	-0.004	0.093	-10000	0	-0.68	3	3
EOMES	-0.16	0.45	-10000	0	-1.5	39	39
STAT1 (dimer)	-0.14	0.37	-10000	0	-0.77	79	79
T cell proliferation	-0.055	0.27	-10000	0	-0.6	50	50
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.028	0.15	-10000	0	-0.42	41	41
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.15	0.25	-10000	0	-0.68	54	54
ATF2	-0.072	0.33	-10000	0	-0.75	52	52

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.014	0.001	-9999	-10000	0	0
HDAC2	0.014	0.001	-9999	-10000	0	0
GNB1/GNG2	0	0	-9999	-10000	0	0
forebrain development	-0.32	0.28	-9999	-0.56	214	214
GNAO1	-0.019	0.15	-9999	-0.72	16	16
SMO/beta Arrestin2	0.012	0.012	-9999	-10000	0	0
SMO	0.008	0.008	-9999	-10000	0	0
ARRB2	0.007	0.007	-9999	-10000	0	0
GLI3/SPOP	0.048	0.044	-9999	-10000	0	0
mol:GTP	-0.002	0.003	-9999	-10000	0	0
GSK3B	0.013	0	-9999	-10000	0	0
GNAI2	0.01	0.006	-9999	-10000	0	0
SIN3/HDAC complex	0.009	0.032	-9999	-0.52	1	1
GNAI1	0.01	0.005	-9999	-10000	0	0
XPO1	0.008	0.008	-9999	-10000	0	0
GLI1/Su(fu)	-0.25	0.19	-9999	-0.51	113	113
SAP30	0.012	0.043	-9999	-0.85	1	1
mol:GDP	0.008	0.008	-9999	-10000	0	0
MIM/GLI2A	-0.009	0.044	-9999	-10000	0	0
IFT88	0.013	0	-9999	-10000	0	0
GNAI3	0.01	0.005	-9999	-10000	0	0
GLI2	0.033	0.063	-9999	-10000	0	0
GLI3	0.043	0.046	-9999	-0.31	7	7
CSNK1D	0.013	0	-9999	-10000	0	0
CSNK1E	0.013	0	-9999	-10000	0	0
SAP18	0.014	0.001	-9999	-10000	0	0
embryonic digit morphogenesis	0.013	0	-9999	-10000	0	0
GNG2	0.013	0	-9999	-10000	0	0
Gi family/GTP	0.009	0.065	-9999	-0.34	12	12
SIN3B	0.014	0.001	-9999	-10000	0	0
SIN3A	0.014	0.001	-9999	-10000	0	0
GLI3/Su(fu)	0.03	0.045	-9999	-10000	0	0
GLI2/Su(fu)	0.022	0.059	-9999	-10000	0	0
FOXA2	-0.69	0.67	-9999	-1.4	203	203
neural tube patterning	-0.32	0.28	-9999	-0.56	214	214
SPOP	0.013	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.018	0.018	-9999	-10000	0	0
GNB1	0.013	0	-9999	-10000	0	0
CSNK1G2	0.013	0	-9999	-10000	0	0
CSNK1G3	0.013	0	-9999	-10000	0	0
MTSS1	-0.008	0.044	-9999	-10000	0	0
embryonic limb morphogenesis	-0.32	0.28	-9999	-0.56	214	214
SUFU	0.017	0.017	-9999	-10000	0	0
LGALS3	-0.11	0.16	-9999	-0.31	149	149
catabolic process	0.064	0.061	-9999	-0.4	1	1
GLI3A/CBP	-0.2	0.2	-9999	-0.39	214	214
KIF3A	0.013	0	-9999	-10000	0	0
GLI1	-0.33	0.29	-9999	-0.57	214	214
RAB23	0.007	0.074	-9999	-0.85	3	3
CSNK1A1	0.013	0	-9999	-10000	0	0
IFT172	0.013	0	-9999	-10000	0	0
RBBP7	0.014	0.001	-9999	-10000	0	0
Su(fu)/Galectin3	-0.036	0.077	-9999	-10000	0	0
GNAZ	0.01	0.005	-9999	-10000	0	0
RBBP4	0.014	0.001	-9999	-10000	0	0
CSNK1G1	0.013	0	-9999	-10000	0	0
PIAS1	0.013	0	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
GLI2/SPOP	0.037	0.058	-9999	-10000	0	0
STK36	0.008	0.008	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.015	0.055	-9999	-10000	0	0
PTCH1	-0.29	0.26	-9999	-0.62	113	113
MIM/GLI1	-0.46	0.39	-9999	-0.76	212	212
CREBBP	-0.2	0.2	-9999	-0.39	214	214
Su(fu)/SIN3/HDAC complex	0.057	0.017	-9999	-10000	0	0

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.044	0.12	-9999	-0.55	15	15
alphaM/beta2 Integrin/GPIbA	-0.057	0.15	-9999	-0.59	24	24
alphaM/beta2 Integrin/proMMP-9	-0.097	0.21	-9999	-0.62	47	47
PLAUR	-0.095	0.15	-9999	-0.31	136	136
HMGB1	0.002	0.024	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.037	0.11	-9999	-0.44	20	20
AGER	-0.072	0.24	-9999	-0.83	36	36
RAP1A	0.013	0	-9999	-10000	0	0
SELPLG	-0.007	0.078	-9999	-0.31	25	25
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.13	0.21	-9999	-0.66	39	39
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.084	0.25	-9999	-0.59	66	66
CYR61	-0.25	0.4	-9999	-0.85	124	124
TLN1	0.013	0	-9999	-10000	0	0
Rap1/GTP	-0.076	0.098	-9999	-0.45	10	10
RHOA	0.013	0	-9999	-10000	0	0
P-selectin oligomer	-0.004	0.11	-9999	-0.6	11	11
MYH2	-0.11	0.12	-9999	-0.42	34	34
MST1R	-0.006	0.12	-9999	-0.7	11	11
leukocyte activation during inflammatory response	-0.041	0.1	-9999	-0.64	5	5
APOB	-0.006	0.07	-9999	-0.31	20	20
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	0.002	0.089	-9999	-0.62	7	7
JAM3	0.013	0	-9999	-10000	0	0
GP1BA	-0.019	0.15	-9999	-0.64	20	20
alphaM/beta2 Integrin/CTGF	-0.12	0.23	-9999	-0.61	69	69
alphaM/beta2 Integrin	-0.1	0.12	-9999	-0.36	44	44
JAM3 homodimer	0.013	0	-9999	-10000	0	0
ICAM2	0.013	0	-9999	-10000	0	0
ICAM1	-0.087	0.15	-9999	-0.31	125	125
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.099	0.12	-9999	-0.36	44	44
cell adhesion	-0.057	0.15	-9999	-0.59	24	24
NFKB1	-0.15	0.31	-9999	-0.76	56	56
THY1	0.011	0.028	-9999	-0.31	3	3
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.012	0.047	-9999	-0.34	2	2
alphaM/beta2 Integrin/LRP/tPA	-0.036	0.11	-9999	-0.62	8	8
IL6	-0.26	0.48	-9999	-1.1	91	91
ITGB2	-0.021	0.091	-9999	-0.34	26	26
elevation of cytosolic calcium ion concentration	-0.14	0.17	-9999	-0.55	31	31
alphaM/beta2 Integrin/JAM2/JAM3	-0.035	0.11	-9999	-0.63	9	9
JAM2	0.004	0.086	-9999	-0.74	5	5
alphaM/beta2 Integrin/ICAM1	-0.076	0.14	-9999	-0.51	25	25
alphaM/beta2 Integrin/uPA/Plg	-0.098	0.13	-9999	-0.52	20	20
RhoA/GTP	-0.11	0.13	-9999	-0.43	39	39
positive regulation of phagocytosis	-0.074	0.12	-9999	-0.49	17	17
Ron/MSP	-0.016	0.098	-9999	-0.66	9	9
alphaM/beta2 Integrin/uPAR/uPA	-0.14	0.17	-9999	-0.56	31	31
alphaM/beta2 Integrin/uPAR	-0.09	0.14	-9999	-0.47	31	31
PLAU	-0.14	0.16	-9999	-10000	0	0
PLAT	0.002	0.075	-9999	-0.42	10	10
actin filament polymerization	-0.1	0.12	-9999	-0.4	34	34
MST1	0.01	0.046	-9999	-0.58	2	2
alphaM/beta2 Integrin/lipoprotein(a)	-0.041	0.1	-9999	-0.65	5	5
TNF	-0.19	0.41	-9999	-1	64	64
RAP1B	0.013	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.11	0.14	-9999	-0.56	20	20
fibrinolysis	-0.098	0.13	-9999	-0.51	20	20
HCK	-0.008	0.08	-9999	-0.31	26	26
dendritic cell antigen processing and presentation	-0.099	0.12	-9999	-0.36	44	44
VTN	-0.078	0.26	-9999	-0.79	46	46
alphaM/beta2 Integrin/CYR61	-0.21	0.29	-9999	-0.6	138	138
LPA	-0.003	0.047	-9999	-0.31	9	9
LRP1	0.011	0.043	-9999	-0.85	1	1
cell migration	-0.091	0.21	-9999	-0.62	45	45
FN1	-0.22	0.15	-9999	-0.31	295	295
alphaM/beta2 Integrin/Thy1	-0.038	0.11	-9999	-0.53	11	11
MPO	-0.005	0.11	-9999	-0.73	9	9
KNG1	-0.013	0.075	-9999	-10000	0	0
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.099	0.12	-9999	-0.43	27	27
ELA2	0	0	-9999	-10000	0	0
PLG	0	0.022	-9999	-0.31	2	2
CTGF	-0.11	0.3	-9999	-0.85	59	59
alphaM/beta2 Integrin/Hck	-0.048	0.13	-9999	-0.55	20	20
ITGAM	-0.026	0.12	-9999	-0.4	27	27
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.049	0.14	-9999	-0.53	25	25
HP	-0.077	0.17	-9999	-0.34	103	103
leukocyte adhesion	-0.1	0.17	-9999	-0.64	24	24
SELP	-0.004	0.11	-9999	-0.61	11	11

×

IL6-mediated signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.055	0.2	-9999	-0.62	21	21
CRP	-0.06	0.2	-9999	-0.66	17	17
cell cycle arrest	-0.076	0.23	-9999	-0.72	23	23
TIMP1	-0.15	0.2	-9999	-0.58	30	30
IL6ST	-0.092	0.28	-9999	-0.85	49	49
Rac1/GDP	-0.087	0.24	-9999	-0.58	51	51
AP1	-0.2	0.33	-9999	-0.7	114	114
GAB2	0.014	0.001	-9999	-10000	0	0
TNFSF11	-0.099	0.22	-9999	-0.64	21	21
HSP90B1	0.022	0.041	-9999	-10000	0	0
GAB1	0.014	0	-9999	-10000	0	0
MAPK14	-0.1	0.31	-9999	-0.82	48	48
AKT1	0.055	0.021	-9999	-10000	0	0
FOXO1	0.062	0.02	-9999	-10000	0	0
MAP2K6	-0.1	0.29	-9999	-0.7	53	53
mol:GTP	0	0.001	-9999	-10000	0	0
MAP2K4	-0.077	0.23	-9999	-0.63	34	34
MITF	-0.089	0.26	-9999	-0.57	57	57
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0.013	0	-9999	-10000	0	0
A2M	0.025	0.006	-9999	-10000	0	0
CEBPB	0.022	0.002	-9999	-10000	0	0
GRB2/SOS1/GAB family/SHP2	-0.026	0.078	-9999	-10000	0	0
STAT3	-0.088	0.24	-9999	-0.78	23	23
STAT1	-0.011	0.022	-9999	-10000	0	0
CEBPD	-0.055	0.2	-9999	-0.68	13	13
PIK3CA	0.013	0.043	-9999	-0.85	1	1
PI3K	-0.002	0.032	-9999	-0.66	1	1
JUN	-0.18	0.36	-9999	-0.85	93	93
PIAS3/MITF	-0.078	0.24	-9999	-0.58	47	47
MAPK11	-0.1	0.31	-9999	-0.83	47	47
STAT3 (dimer)/FOXO1	-0.005	0.19	-9999	-0.59	12	12
GRB2/SOS1/GAB family	-0.11	0.19	-9999	-0.77	16	16
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.12	0.25	-9999	-0.48	92	92
GRB2	0.014	0	-9999	-10000	0	0
JAK2	0.013	0	-9999	-10000	0	0
LBP	-0.061	0.19	-9999	-0.58	13	13
PIK3R1	0.014	0	-9999	-10000	0	0
JAK1	0.013	0.005	-9999	-10000	0	0
MYC	-0.069	0.25	-9999	-1	14	14
FGG	-0.063	0.2	-9999	-0.63	22	22
macrophage differentiation	-0.076	0.23	-9999	-0.72	23	23
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.19	0.28	-9999	-0.56	130	130
JUNB	-0.062	0.23	-9999	-0.72	24	24
FOS	-0.21	0.38	-9999	-0.85	106	106
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.099	0.27	-9999	-0.54	76	76
STAT1/PIAS1	-0.081	0.23	-9999	-0.6	37	37
GRB2/SOS1/GAB family/SHP2/PI3K	0.036	0.027	-9999	-0.32	1	1
STAT3 (dimer)	-0.085	0.23	-9999	-0.76	23	23
PRKCD	-0.064	0.22	-9999	-0.64	27	27
IL6R	-0.01	0.14	-9999	-0.85	11	11
SOCS3	-0.13	0.41	-9999	-1.2	46	46
gp130 (dimer)/JAK1/JAK1/LMO4	-0.052	0.19	-9999	-0.57	49	49
Rac1/GTP	-0.11	0.23	-9999	-0.58	51	51
HCK	-0.008	0.08	-9999	-0.31	26	26
MAPKKK cascade	0.011	0.06	-9999	-10000	0	0
bone resorption	-0.094	0.21	-9999	-0.6	23	23
IRF1	-0.055	0.2	-9999	-0.66	15	15
mol:GDP	-0.099	0.26	-9999	-0.58	59	59
SOS1	0.013	0.001	-9999	-10000	0	0
VAV1	-0.1	0.26	-9999	-0.6	59	59
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.11	0.31	-9999	-0.8	49	49
PTPN11	-0.009	0.018	-9999	-10000	0	0
IL6/IL6RA	-0.16	0.29	-9999	-0.68	96	96
gp130 (dimer)/TYK2/TYK2/LMO4	-0.057	0.19	-9999	-0.57	49	49
gp130 (dimer)/JAK2/JAK2/LMO4	-0.057	0.19	-9999	-0.57	49	49
IL6	-0.19	0.35	-9999	-0.77	104	104
PIAS3	0.013	0	-9999	-10000	0	0
PTPRE	-0.095	0.15	-9999	-0.33	57	57
PIAS1	0.013	0	-9999	-10000	0	0
RAC1	0.013	0.001	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.099	0.26	-9999	-0.44	114	114
LMO4	0.011	0.01	-9999	-10000	0	0
STAT3 (dimer)/PIAS3	-0.1	0.22	-9999	-0.77	23	23
MCL1	0.061	0.019	-9999	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.097	0.22	-9999	-0.41	122	122
MAP3K8	-0.003	0.1	-9999	-0.86	6	6
FOS	-0.062	0.17	-9999	-0.5	30	30
PRKCA	-0.04	0.2	-9999	-0.85	24	24
PTPN7	-0.047	0.18	-9999	-0.49	48	48
HRAS	0.011	0.023	-9999	-0.31	2	2
PRKCB	-0.026	0.11	-9999	-0.34	42	42
NRAS	0.012	0.002	-9999	-10000	0	0
RAS family/GTP	-0.001	0.01	-9999	-10000	0	0
MAPK3	-0.034	0.13	-9999	-0.54	15	15
MAP2K1	-0.029	0.16	-9999	-0.58	25	25
ELK1	0.008	0.01	-9999	-10000	0	0
BRAF	-0.049	0.14	-9999	-0.58	25	25
mol:GTP	-0.001	0.003	-9999	-0.006	106	106
MAPK1	-0.034	0.13	-9999	-0.54	15	15
RAF1	-0.049	0.14	-9999	-0.58	25	25
KRAS	0.012	0.002	-9999	-10000	0	0

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.012	0.023	-9999	-0.31	2	2
EGFR	0.003	0.095	-9999	-0.85	5	5
EGF/EGFR	-0.08	0.18	-9999	-0.48	66	66
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.073	0.17	-9999	-0.48	60	60
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.009	0.051	-9999	-0.45	4	4
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.11	0.3	-9999	-0.8	61	61
EGF/EGFR dimer/SHC	-0.086	0.2	-9999	-0.57	60	60
mol:GDP	-0.072	0.17	-9999	-0.48	60	60
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.001	0.097	-9999	-0.7	7	7
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.067	0.16	-9999	-0.44	60	60
SHC1	0.013	0	-9999	-10000	0	0
HRAS/GDP	-0.068	0.16	-9999	-0.45	60	60
FRAP1	-0.036	0.18	-9999	-0.46	60	60
EGF/EGFR dimer	-0.099	0.23	-9999	-0.66	60	60
SOS1	0.013	0	-9999	-10000	0	0
GRB2	0.013	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.012	0.083	-9999	-0.62	7	7

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.034	0.15	-9999	-0.49	33	33
NF kappa B1 p50/RelA/I kappa B alpha	-0.055	0.12	-9999	-0.57	6	6
alphaV/beta3 Integrin/Osteopontin/Src	-0.067	0.15	-9999	-0.64	21	21
AP1	-0.26	0.37	-9999	-0.88	94	94
ILK	-0.038	0.16	-9999	-0.52	33	33
bone resorption	-0.057	0.14	-9999	-0.63	9	9
PTK2B	0.013	0	-9999	-10000	0	0
PYK2/p130Cas	-0.054	0.13	-9999	-0.47	33	33
ITGAV	0.011	0.043	-9999	-0.85	1	1
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.016	0.1	-9999	-0.66	10	10
alphaV/beta3 Integrin/Osteopontin	-0.072	0.16	-9999	-0.58	33	33
MAP3K1	-0.035	0.16	-9999	-0.53	33	33
JUN	-0.18	0.36	-9999	-0.85	93	93
MAPK3	-0.034	0.16	-9999	-0.49	33	33
MAPK1	-0.034	0.16	-9999	-0.49	33	33
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0.013	0	-9999	-10000	0	0
MAPK8	-0.027	0.16	-9999	-0.52	34	34
ITGB3	-0.014	0.15	-9999	-0.84	13	13
NFKBIA	-0.027	0.15	-9999	-0.47	33	33
FOS	-0.21	0.38	-9999	-0.85	106	106
CD44	0.013	0	-9999	-10000	0	0
CHUK	0.013	0	-9999	-10000	0	0
PLAU	-0.1	0.18	-9999	-0.72	4	4
NF kappa B1 p50/RelA	-0.06	0.11	-9999	-0.56	6	6
BCAR1	0.013	0	-9999	-10000	0	0
RELA	0.013	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.022	0.12	-9999	-0.69	13	13
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.034	0.16	-9999	-0.53	33	33
VAV3	-0.028	0.16	-9999	-0.5	36	36
MAP3K14	-0.042	0.16	-9999	-0.53	33	33
ROCK2	-0.008	0.13	-9999	-0.85	10	10
SPP1	-0.083	0.21	-9999	-0.43	88	88
RAC1	0.013	0	-9999	-10000	0	0
Rac1/GTP	-0.056	0.14	-9999	-0.46	36	36
MMP2	-0.17	0.3	-9999	-0.67	90	90

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	-0.039	0.12	-10000	0	-0.31	62	62
GNB1/GNG2	-0.044	0.067	-10000	0	-0.2	33	33
AKT1	-0.014	0.1	-10000	0	-0.21	26	26
EGF	-0.11	0.3	-10000	0	-0.8	61	61
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.008	0.069	-10000	0	-0.59	1	1
mol:Ca2+	-0.044	0.14	-10000	0	-0.31	59	59
LYN	0.01	0.068	-10000	0	-0.59	1	1
RhoA/GTP	-0.031	0.044	-10000	0	-10000	0	0
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.044	0.16	-10000	0	-0.35	56	56
GNG2	0.013	0	-10000	0	-10000	0	0
ARRB2	0.013	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.02	0.11	-10000	0	-0.55	5	5
G beta5/gamma2	-0.059	0.091	-10000	0	-0.27	38	38
PRKCH	-0.052	0.16	-10000	0	-0.36	57	57
DNM1	-0.026	0.18	-10000	0	-0.82	19	19
TXA2/TP beta/beta Arrestin3	-0.016	0.064	-10000	0	-0.31	18	18
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	-0.023	0.17	-10000	0	-0.85	17	17
G12 family/GTP	-0.077	0.11	-10000	0	-0.31	56	56
ADRBK1	0.013	0	-10000	0	-10000	0	0
ADRBK2	0.013	0	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0	0	-10000	0	-10000	0	0
mol:GDP	0.018	0.1	0.34	14	-10000	0	14
mol:NADP	0.013	0	-10000	0	-10000	0	0
RAB11A	0.013	0	-10000	0	-10000	0	0
PRKG1	-0.22	0.38	-10000	0	-0.85	108	108
mol:IP3	-0.06	0.17	-10000	0	-0.39	59	59
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	-0.087	0.22	-10000	0	-0.53	59	59
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.12	0.2	-10000	0	-0.41	123	123
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.002	0.071	-10000	0	-0.59	1	1
RHOA	0.013	0	-10000	0	-10000	0	0
PTGIR	0.005	0.085	-10000	0	-0.85	4	4
PRKCB1	-0.06	0.17	-10000	0	-0.39	59	59
GNAQ	0.013	0	-10000	0	-10000	0	0
mol:L-citrulline	0.013	0	-10000	0	-10000	0	0
TXA2/TXA2-R family	-0.084	0.23	-10000	0	-0.54	60	60
LCK	0	0.088	-10000	0	-0.5	6	6
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.017	0.078	-10000	0	-0.84	1	1
TXA2-R family/G12 family/GDP/G beta/gamma	0.029	0.025	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.017	0.077	-10000	0	-0.83	1	1
MAPK14	-0.019	0.11	-10000	0	-0.23	47	47
TGM2/GTP	-0.073	0.2	-10000	0	-0.44	59	59
MAPK11	-0.019	0.11	-10000	0	-0.23	37	37
ARHGEF1	-0.015	0.087	-10000	0	-0.2	2	2
GNAI2	0.013	0	-10000	0	-10000	0	0
JNK cascade	-0.057	0.18	-10000	0	-0.39	60	60
RAB11/GDP	0.013	0.001	-10000	0	-10000	0	0
ICAM1	-0.052	0.15	-10000	0	-0.3	64	64
cAMP biosynthetic process	-0.059	0.16	-10000	0	-0.36	57	57
Gq family/GTP/EBP50	-0.039	0.12	-10000	0	-0.25	95	95
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0.009	0.068	-10000	0	-0.59	1	1
GNB5	0.013	0	-10000	0	-10000	0	0
GNB1	0.013	0	-10000	0	-10000	0	0
EGF/EGFR	-0.02	0.1	-10000	0	-0.31	14	14
VCAM1	-0.038	0.14	-10000	0	-0.3	59	59
TP beta/Gq family/GDP/G beta5/gamma2	-0.02	0.11	-10000	0	-0.55	5	5
platelet activation	-0.026	0.15	-10000	0	-0.31	55	55
PGI2/IP	-0.007	0.066	-10000	0	-0.67	4	4
PRKACA	-0.001	0.1	-10000	0	-0.43	20	20
Gq family/GDP/G beta5/gamma2	-0.022	0.11	-10000	0	-0.52	5	5
TXA2/TP beta/beta Arrestin2	-0.031	0.14	-10000	0	-0.68	18	18
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.009	0.097	-10000	0	-0.4	20	20
mol:DAG	-0.068	0.19	-10000	0	-0.44	58	58
EGFR	0.003	0.095	-10000	0	-0.85	5	5
TXA2/TP alpha	-0.082	0.22	-10000	0	-0.5	57	57
Gq family/GTP	-0.073	0.13	-10000	0	-0.31	95	95
YES1	0.01	0.068	-10000	0	-0.59	1	1
GNAI2/GTP	-0.015	0.07	-10000	0	-0.72	1	1
PGD2/DP	-0.028	0.13	-10000	0	-0.67	17	17
SLC9A3R1	0.012	0.023	-10000	0	-0.31	2	2
FYN	0.01	0.068	-10000	0	-0.59	1	1
mol:NO	0.013	0	-10000	0	-10000	0	0
GNA15	-0.012	0.094	-10000	0	-0.33	30	30
PGK/cGMP	-0.15	0.26	-10000	0	-0.58	108	108
RhoA/GDP	0.013	0.001	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.03	0.087	-10000	0	-0.54	5	5
NOS3	0.013	0	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
PRKCA	-0.068	0.18	-10000	0	-0.39	71	71
PRKCB	-0.061	0.16	-10000	0	-0.37	60	60
PRKCE	-0.054	0.17	-10000	0	-0.38	57	57
PRKCD	-0.054	0.17	-10000	0	-0.39	57	57
PRKCG	-0.059	0.17	-10000	0	-0.4	58	58
muscle contraction	-0.074	0.21	-10000	0	-0.49	60	60
PRKCZ	-0.044	0.16	-10000	0	-0.35	56	56
ARR3	0.004	0.006	-10000	0	-10000	0	0
TXA2/TP beta	-0.017	0.079	-10000	0	-0.85	1	1
PRKCQ	-0.054	0.17	-10000	0	-0.37	61	61
MAPKKK cascade	-0.075	0.2	-10000	0	-0.47	60	60
SELE	-0.057	0.17	-10000	0	-0.43	57	57
TP beta/GNAI2/GDP/G beta/gamma	-0.017	0.076	-10000	0	-0.83	1	1
ROCK1	0.013	0	-10000	0	-10000	0	0
GNA14	-0.18	0.36	-10000	0	-0.85	92	92
chemotaxis	-0.096	0.25	-10000	0	-0.62	59	59
GNA12	0.013	0	-10000	0	-10000	0	0
GNA13	0.013	0	-10000	0	-10000	0	0
GNA11	0.005	0.085	-10000	0	-0.85	4	4
Rac1/GTP	0	0	-10000	0	-10000	0	0

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.081	0.11	-9999	-0.21	169	169
TP53	-0.027	0.032	-9999	-10000	0	0
Senescence	-0.027	0.032	-9999	-10000	0	0
Apoptosis	-0.027	0.032	-9999	-10000	0	0
Activated_Oncogenes	0	0	-9999	-10000	0	0
MDM2	0.052	0.062	-9999	-10000	0	0
MDM4	0.013	0	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.081	0.099	-10000	0	-10000	0	0
CRKL	-0.035	0.12	-10000	0	-0.34	25	25
mol:PIP3	-0.018	0.036	0.71	1	-10000	0	1
AKT1	0.002	0.036	0.46	1	-0.56	1	2
PTK2B	0.013	0	-10000	0	-10000	0	0
RAPGEF1	-0.026	0.11	-10000	0	-10000	0	0
RANBP10	0.013	0	-10000	0	-10000	0	0
PIK3CA	0.011	0.043	-10000	0	-0.85	1	1
HGF/MET/SHIP2	-0.15	0.22	-10000	0	-0.63	62	62
MAP3K5	-0.023	0.12	-10000	0	-0.49	5	5
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.13	0.2	-10000	0	-0.58	62	62
AP1	-0.29	0.44	-10000	0	-0.93	124	124
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.013	0	-10000	0	-10000	0	0
apoptosis	-0.26	0.4	-10000	0	-0.86	124	124
STAT3 (dimer)	-0.044	0.14	-10000	0	-0.35	62	62
GAB1/CRKL/SHP2/PI3K	-0.043	0.089	-10000	0	-0.4	1	1
INPP5D	-0.005	0.075	-10000	0	-0.31	23	23
CBL/CRK	-0.026	0.11	-10000	0	-10000	0	0
PTPN11	0.013	0	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.013	0	-10000	0	-10000	0	0
PTEN	0.011	0.043	-10000	0	-0.85	1	1
ELK1	-0.053	0.063	-10000	0	-10000	0	0
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.041	0.074	-10000	0	-0.25	25	25
PAK1	0.01	0.034	0.43	1	-0.52	1	2
HGF/MET/RANBP10	-0.15	0.22	-10000	0	-0.63	62	62
HRAS	-0.064	0.17	-10000	0	-0.44	62	62
DOCK1	-0.028	0.12	-10000	0	-0.58	2	2
GAB1	-0.046	0.12	-10000	0	-0.31	62	62
CRK	-0.035	0.12	-10000	0	-0.34	25	25
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.12	0.22	-10000	0	-0.62	62	62
JUN	-0.18	0.36	-10000	0	-0.85	93	93
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.075	0.1	-10000	0	-0.3	62	62
PIK3R1	0.013	0	-10000	0	-10000	0	0
cell morphogenesis	-0.013	0.14	-10000	0	-10000	0	0
GRB2/SHC	-0.058	0.088	-10000	0	-10000	0	0
FOS	-0.21	0.38	-10000	0	-0.85	106	106
GLMN	0	0	-10000	0	-10000	0	0
cell motility	-0.053	0.063	-10000	0	-10000	0	0
HGF/MET/MUC20	-0.15	0.22	-10000	0	-0.64	62	62
cell migration	-0.058	0.087	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
CBL	0.013	0	-10000	0	-10000	0	0
MET/RANBP10	-0.081	0.099	-10000	0	-10000	0	0
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.056	0.14	-10000	0	-0.38	62	62
MET/MUC20	-0.085	0.1	-10000	0	-0.21	164	164
RAP1B	-0.016	0.1	-10000	0	-10000	0	0
RAP1A	-0.016	0.1	-10000	0	-10000	0	0
HGF/MET/RANBP9	-0.15	0.22	-10000	0	-0.63	62	62
RAF1	-0.053	0.16	-10000	0	-0.46	26	26
STAT3	-0.045	0.14	-10000	0	-0.35	62	62
cell proliferation	-0.053	0.18	-10000	0	-0.47	62	62
RPS6KB1	-0.017	0.041	-10000	0	-10000	0	0
MAPK3	-0.053	0.058	-10000	0	-10000	0	0
MAPK1	-0.053	0.058	-10000	0	-10000	0	0
RANBP9	0.013	0	-10000	0	-10000	0	0
MAPK8	-0.003	0.11	-10000	0	-0.51	7	7
SRC	-0.045	0.14	-10000	0	-0.4	25	25
PI3K	-0.059	0.091	-10000	0	-0.48	1	1
MET/Glomulin	-0.065	0.095	-10000	0	-10000	0	0
SOS1	0.013	0	-10000	0	-10000	0	0
MAP2K1	-0.041	0.15	-10000	0	-0.43	26	26
MET	-0.12	0.16	-10000	0	-0.31	164	164
MAP4K1	-0.031	0.12	-10000	0	-0.34	30	30
PTK2	0.013	0	-10000	0	-10000	0	0
MAP2K2	-0.041	0.15	-10000	0	-0.43	26	26
BAD	0.01	0.034	0.43	1	-0.52	1	2
MAP2K4	-0.013	0.11	-10000	0	-0.44	5	5
SHP2/GRB2/SOS1/GAB1	-0.06	0.094	-10000	0	-10000	0	0
INPPL1	0.013	0	-10000	0	-10000	0	0
PXN	0.013	0	-10000	0	-10000	0	0
SH3KBP1	0.013	0	-10000	0	-10000	0	0
HGS	-0.053	0.1	-10000	0	-0.33	25	25
PLCgamma1/PKC	0	0	-10000	0	-10000	0	0
HGF	-0.12	0.31	-10000	0	-0.85	62	62
RASA1	0.013	0	-10000	0	-10000	0	0
NCK1	0.013	0	-10000	0	-10000	0	0
PTPRJ	0.013	0	-10000	0	-10000	0	0
NCK/PLCgamma1	-0.045	0.11	-10000	0	-0.34	25	25
PDPK1	-0.008	0.04	0.53	1	-0.6	1	2
HGF/MET/SHIP	-0.16	0.22	-10000	0	-0.63	62	62

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.023	0.074	0.3	26	-10000	0	26
RFC1	0.023	0.074	0.3	26	-10000	0	26
PRKDC	0.023	0.074	0.3	26	-10000	0	26
RIPK1	0.014	0.005	-10000	0	-10000	0	0
CASP7	-0.015	0.047	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1	-0.033	0.11	0.26	2	-0.38	31	33
MAP2K4	-0.031	0.16	-10000	0	-0.54	15	15
mol:ceramide	-0.029	0.15	-10000	0	-0.5	31	31
GSN	0.023	0.074	0.3	26	-10000	0	26
FASLG/FAS/FADD/FAF1/Caspase 8	-0.026	0.14	-10000	0	-0.48	31	31
FAS	0.01	0.006	-10000	0	-10000	0	0
BID	-0.035	0.083	0.32	3	-10000	0	3
MAP3K1	-0.001	0.1	-10000	0	-10000	0	0
MAP3K7	0.01	0.006	-10000	0	-10000	0	0
RB1	0.023	0.074	0.3	26	-10000	0	26
CFLAR	0.014	0.005	-10000	0	-10000	0	0
HGF/MET	-0.15	0.22	-10000	0	-0.64	63	63
ARHGDIB	0.019	0.079	0.3	26	-10000	0	26
FADD	0.01	0.006	-10000	0	-10000	0	0
actin filament polymerization	-0.023	0.074	-10000	0	-0.3	26	26
NFKB1	-0.055	0.09	-10000	0	-0.29	15	15
MAPK8	-0.063	0.22	-10000	0	-0.46	83	83
DFFA	0.023	0.074	0.3	26	-10000	0	26
DNA fragmentation during apoptosis	0.023	0.074	0.3	26	-10000	0	26
FAS/FADD/MET	-0.064	0.078	-10000	0	-10000	0	0
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	-0.004	0.095	-10000	0	-0.85	3	3
FAF1	0.011	0.007	-10000	0	-10000	0	0
PARP1	0.023	0.074	0.3	26	-10000	0	26
DFFB	0.023	0.074	0.3	26	-10000	0	26
CHUK	-0.047	0.079	-10000	0	-10000	0	0
FASLG	-0.065	0.23	-10000	0	-0.71	43	43
FAS/FADD	0	0.001	-10000	0	-10000	0	0
HGF	-0.12	0.31	-10000	0	-0.85	62	62
LMNA	0.021	0.068	0.27	26	-10000	0	26
CASP6	0.023	0.074	0.3	26	-10000	0	26
CASP10	0.01	0.006	-10000	0	-10000	0	0
CASP3	0.027	0.09	0.35	29	-10000	0	29
PTPN13	0.009	0.06	-10000	0	-0.85	2	2
CASP8	0.009	0.048	0.46	3	-10000	0	3
IL6	-0.28	0.58	-10000	0	-1.4	88	88
MET	-0.12	0.16	-10000	0	-0.31	164	164
ICAD/CAD	0.021	0.069	0.28	26	-10000	0	26
FASLG/FAS/FADD/FAF1/Caspase 10	-0.03	0.16	-10000	0	-0.5	31	31
activation of caspase activity by cytochrome c	-0.035	0.083	0.32	3	-10000	0	3
PAK2	0.023	0.074	0.3	26	-10000	0	26
BCL2	-0.041	0.21	-10000	0	-0.85	26	26

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.12	0.11	-9999	-0.67	6	6
EPHB2	0.007	0.074	-9999	-0.85	3	3
Syndecan-2/TACI	-0.14	0.27	-9999	-0.59	108	108
LAMA1	-0.053	0.23	-9999	-0.83	32	32
Syndecan-2/alpha2 ITGB1	-0.073	0.11	-9999	-0.49	18	18
HRAS	0.012	0.023	-9999	-0.31	2	2
Syndecan-2/CASK	-0.008	0.069	-9999	-0.57	6	6
ITGA5	0.013	0	-9999	-10000	0	0
BAX	0.031	0.08	-9999	-0.5	9	9
EPB41	0.013	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.008	0.063	-9999	-0.52	6	6
LAMA3	-0.023	0.16	-9999	-0.56	26	26
EZR	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	0.009	0.06	-9999	-0.85	2	2
Syndecan-2/MMP2	0.01	0.093	-9999	-0.57	10	10
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.082	0.099	-9999	-10000	0	0
dendrite morphogenesis	0.013	0.087	-9999	-0.57	9	9
Syndecan-2/GM-CSF	-0.11	0.1	-9999	-0.6	6	6
determination of left/right symmetry	0.011	0.081	-9999	-0.65	6	6
Syndecan-2/PKC delta	0.017	0.071	-9999	-0.57	6	6
GNB2L1	0.013	0	-9999	-10000	0	0
MAPK3	-0.087	0.094	-9999	-0.54	6	6
MAPK1	-0.087	0.094	-9999	-0.54	6	6
Syndecan-2/RACK1	-0.008	0.06	-9999	-0.49	6	6
NF1	0.013	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.011	0.081	-9999	-0.65	6	6
ITGA2	-0.12	0.16	-9999	-0.31	166	166
MAPK8	0.024	0.088	-9999	-0.56	9	9
Syndecan-2/alpha2/beta1 Integrin	-0.091	0.15	-9999	-0.55	34	34
Syndecan-2/Kininogen	-0.007	0.081	-9999	-0.57	6	6
ITGB1	0.013	0	-9999	-10000	0	0
SRC	0.031	0.061	-9999	-0.46	6	6
Syndecan-2/CASK/Protein 4.1	-0.008	0.063	-9999	-0.52	6	6
extracellular matrix organization	0.014	0.074	-9999	-0.56	6	6
actin cytoskeleton reorganization	-0.12	0.11	-9999	-0.66	6	6
Syndecan-2/Caveolin-2/Ras	-0.011	0.08	-9999	-0.59	7	7
Syndecan-2/Laminin alpha3	-0.007	0.12	-9999	-0.57	18	18
Syndecan-2/RasGAP	-0.007	0.056	-9999	-0.47	6	6
alpha5/beta1 Integrin	0	0	-9999	-10000	0	0
PRKCD	0.013	0	-9999	-10000	0	0
Syndecan-2 dimer	0.013	0.087	-9999	-0.57	9	9
GO:0007205	0.004	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.037	0.06	-9999	-0.44	6	6
RHOA	0.013	0	-9999	-10000	0	0
SDCBP	0.013	0	-9999	-10000	0	0
TNFRSF13B	-0.22	0.38	-9999	-0.85	105	105
RASA1	0.013	0	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.082	0.099	-9999	-10000	0	0
Syndecan-2/Synbindin	0.017	0.071	-9999	-0.57	6	6
TGFB1	0.008	0.039	-9999	-0.31	6	6
CASP3	0.027	0.066	-9999	-0.51	6	6
FN1	-0.22	0.15	-9999	-0.31	295	295
Syndecan-2/IL8	-0.04	0.13	-9999	-0.57	14	14
SDC2	0.011	0.081	-9999	-0.66	6	6
KNG1	-0.013	0.075	-9999	-10000	0	0
Syndecan-2/Neurofibromin	0.017	0.071	-9999	-0.57	6	6
TRAPPC4	0.013	0	-9999	-10000	0	0
CSF2	-0.21	0.15	-9999	-0.31	277	277
Syndecan-2/TGFB1	0.014	0.074	-9999	-0.57	6	6
Syndecan-2/Syntenin/PI-4-5-P2	-0.008	0.063	-9999	-0.52	6	6
Syndecan-2/Ezrin	-0.008	0.062	-9999	-0.52	6	6
PRKACA	0.027	0.066	-9999	-0.51	6	6
angiogenesis	-0.04	0.13	-9999	-0.57	14	14
MMP2	0.002	0.089	-9999	-0.62	7	7
IL8	-0.084	0.18	-9999	-0.35	108	108
calcineurin-NFAT signaling pathway	-0.14	0.27	-9999	-0.58	108	108

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.11	0.19	-9999	-0.46	56	56
IKBKB	-0.02	0.071	-9999	-0.28	5	5
AKT1	-0.044	0.1	-9999	-0.27	19	19
IKBKG	-0.019	0.074	-9999	-0.29	5	5
CALM1	-0.037	0.088	-9999	-0.36	2	2
PIK3CA	0.011	0.043	-9999	-0.85	1	1
MAP3K1	-0.079	0.19	-9999	-0.66	15	15
MAP3K7	0.013	0	-9999	-10000	0	0
mol:Ca2+	-0.047	0.092	-9999	-0.38	2	2
DOK1	0.013	0	-9999	-10000	0	0
AP-1	-0.083	0.14	-9999	-0.28	99	99
LYN	0.013	0	-9999	-10000	0	0
BLNK	0.013	0	-9999	-10000	0	0
SHC1	0.013	0	-9999	-10000	0	0
BCR complex	-0.18	0.25	-9999	-0.54	119	119
CD22	-0.16	0.23	-9999	-0.53	91	91
CAMK2G	-0.027	0.083	-9999	-0.33	2	2
CSNK2A1	0.013	0	-9999	-10000	0	0
INPP5D	-0.005	0.075	-9999	-0.31	23	23
SHC/GRB2/SOS1	-0.1	0.16	-9999	-10000	0	0
GO:0007205	-0.048	0.093	-9999	-0.39	2	2
SYK	0.013	0	-9999	-10000	0	0
ELK1	-0.038	0.089	-9999	-0.36	2	2
NFATC1	-0.073	0.16	-9999	-0.56	16	16
B-cell antigen/BCR complex	-0.18	0.25	-9999	-0.54	119	119
PAG1/CSK	-0.002	0.032	-9999	-0.66	1	1
NFKBIB	0.002	0.027	-9999	-0.1	1	1
HRAS	-0.041	0.1	-9999	-0.35	2	2
NFKBIA	0.002	0.027	-9999	-0.1	1	1
NF-kappa-B/RelA/I kappa B beta	0.008	0.023	-9999	-10000	0	0
RasGAP/Csk	-0.15	0.21	-9999	-0.52	83	83
mol:GDP	-0.043	0.085	-9999	-0.35	2	2
PTEN	0.011	0.043	-9999	-0.85	1	1
CD79B	-0.029	0.11	-9999	-0.31	53	53
NF-kappa-B/RelA/I kappa B alpha	0.008	0.022	-9999	-10000	0	0
GRB2	0.013	0	-9999	-10000	0	0
PI3K/BCAP/CD19	-0.092	0.18	-9999	-0.44	67	67
PIK3R1	0.013	0	-9999	-10000	0	0
mol:IP3	-0.054	0.09	-9999	-0.39	2	2
CSK	0.013	0	-9999	-10000	0	0
FOS	-0.15	0.22	-9999	-0.49	108	108
CHUK	-0.019	0.074	-9999	-0.28	6	6
IBTK	0.013	0	-9999	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.069	0.099	-9999	-0.51	8	8
PTPN6	-0.15	0.22	-9999	-0.5	91	91
RELA	0.013	0	-9999	-10000	0	0
BCL2A1	0.003	0.037	-9999	-0.14	18	18
VAV2	-0.14	0.2	-9999	-0.48	63	63
ubiquitin-dependent protein catabolic process	0.007	0.026	-9999	-0.095	1	1
BTK	-0.016	0.15	-9999	-1.2	6	6
CD19	-0.16	0.21	-9999	-0.46	87	87
MAP4K1	-0.02	0.13	-9999	-0.44	30	30
CD72	0.011	0.028	-9999	-0.31	3	3
PAG1	0.011	0.043	-9999	-0.85	1	1
MAPK14	-0.059	0.16	-9999	-0.53	15	15
SH3BP5	0.013	0	-9999	-10000	0	0
PIK3AP1	-0.037	0.091	-9999	-0.33	2	2
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.068	0.18	-9999	-0.44	64	64
RAF1	-0.031	0.097	-9999	-0.33	1	1
RasGAP/p62DOK/SHIP	-0.15	0.21	-9999	-0.5	82	82
CD79A	-0.2	0.32	-9999	-0.53	163	163
re-entry into mitotic cell cycle	-0.081	0.13	-9999	-0.28	97	97
RASA1	0.013	0	-9999	-10000	0	0
MAPK3	-0.011	0.086	-9999	-10000	0	0
MAPK1	-0.011	0.086	-9999	-10000	0	0
CD72/SHP1	-0.11	0.22	-9999	-0.58	45	45
NFKB1	0.013	0	-9999	-10000	0	0
MAPK8	-0.062	0.17	-9999	-0.54	18	18
actin cytoskeleton organization	-0.093	0.18	-9999	-0.7	10	10
NF-kappa-B/RelA	0.022	0.043	-9999	-10000	0	0
Calcineurin	-0.037	0.061	-9999	-10000	0	0
PI3K	-0.14	0.17	-9999	-0.54	28	28
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.058	0.088	-9999	-0.35	2	2
SOS1	0.013	0	-9999	-10000	0	0
Bam32/HPK1	-0.11	0.25	-9999	-1	18	18
DAPP1	-0.14	0.27	-9999	-1.3	14	14
cytokine secretion	-0.068	0.15	-9999	-0.51	16	16
mol:DAG	-0.054	0.09	-9999	-0.39	2	2
PLCG2	0.013	0	-9999	-10000	0	0
MAP2K1	-0.021	0.092	-9999	-10000	0	0
B-cell antigen/BCR complex/FcgammaRIIB	-0.18	0.25	-9999	-0.61	83	83
mol:PI-3-4-5-P3	-0.1	0.12	-9999	-0.37	26	26
ETS1	-0.018	0.078	-9999	-10000	0	0
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.12	0.18	-9999	-0.48	67	67
B-cell antigen/BCR complex/LYN	-0.13	0.21	-9999	-0.51	72	72
MALT1	0.013	0	-9999	-10000	0	0
TRAF6	0.011	0.043	-9999	-0.85	1	1
RAC1	-0.1	0.2	-9999	-0.77	10	10
B-cell antigen/BCR complex/LYN/SYK	-0.16	0.23	-9999	-0.56	84	84
CARD11	-0.078	0.13	-9999	-0.55	11	11
FCGR2B	-0.032	0.19	-9999	-0.76	24	24
PPP3CA	0.013	0	-9999	-10000	0	0
BCL10	0.013	0	-9999	-10000	0	0
IKK complex	-0.001	0.035	-9999	-0.14	1	1
PTPRC	-0.035	0.18	-9999	-0.6	32	32
PDPK1	-0.046	0.1	-9999	-0.27	19	19
PPP3CB	0.013	0	-9999	-10000	0	0
PPP3CC	0.013	0	-9999	-10000	0	0
POU2F2	0.009	0.024	-9999	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.013	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0	0.1	-9999	-0.77	7	7
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.013	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	-0.15	0.16	-9999	-0.28	236	236
response to UV	0	0	-9999	-10000	0	0
YES1	0.013	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	0.013	0	-9999	-10000	0	0
FYN	0.013	0	-9999	-10000	0	0
MAP3K12	0.013	0	-9999	-10000	0	0
FGR	0.01	0.032	-9999	-0.31	4	4
p38 alpha/TAB1	-0.048	0.067	-9999	-0.28	3	3
PRKG1	-0.22	0.38	-9999	-0.85	108	108
DUSP8	0.002	0.083	-9999	-0.49	9	9
PGK/cGMP/p38 alpha	-0.16	0.21	-9999	-0.48	110	110
apoptosis	-0.046	0.065	-9999	-0.29	2	2
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0.013	0	-9999	-10000	0	0
DUSP1	-0.12	0.32	-9999	-0.85	65	65
PAK1	0.013	0	-9999	-10000	0	0
SRC	0.012	0.016	-9999	-0.31	1	1
RAC1/OSM/MEKK3/MKK3	0	0	-9999	-10000	0	0
TRAF6	0.011	0.043	-9999	-0.85	1	1
RAC1	0.013	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	0.013	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	-0.062	0.12	-9999	-0.36	9	9
BLK	-0.26	0.39	-9999	-0.78	143	143
HCK	-0.008	0.08	-9999	-0.31	26	26
MAP2K3	0.013	0	-9999	-10000	0	0
DUSP16	0.013	0	-9999	-10000	0	0
DUSP10	0.009	0.048	-9999	-0.85	1	1
TRAF6/MEKK3	-0.001	0.026	-9999	-0.54	1	1
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	-0.028	0.09	-9999	-0.3	3	3
positive regulation of innate immune response	-0.06	0.13	-9999	-0.39	7	7
LCK	-0.009	0.11	-9999	-0.45	20	20
p38alpha-beta/MKP7	-0.051	0.13	-9999	-0.38	6	6
p38alpha-beta/MKP5	-0.053	0.13	-9999	-0.49	4	4
PGK/cGMP	-0.18	0.29	-9999	-0.67	108	108
PAK2	0.013	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.12	0.2	-9999	-0.48	68	68
CDC42	0.013	0	-9999	-10000	0	0
RALB	0.013	0	-9999	-10000	0	0
RALA	0.013	0	-9999	-10000	0	0
PAK3	-0.49	0.43	-9999	-0.85	236	236

×

Visual signal transduction: Rods

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.013	0	-9999	-10000	0	0
GNAT1/GTP	-0.001	0.015	-9999	-10000	0	0
Metarhodopsin II/Arrestin	-0.001	0.012	-9999	-10000	0	0
PDE6G/GNAT1/GTP	-0.016	0.065	-9999	-0.58	3	3
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.003	0.023	-9999	-0.31	2	2
GRK1	-0.072	0.26	-9999	-0.84	41	41
CNG Channel	-0.028	0.088	-9999	-0.6	5	5
mol:Na +	-0.025	0.09	-9999	-0.5	8	8
mol:ADP	-0.072	0.26	-9999	-0.84	41	41
RGS9-1/Gbeta5/R9AP	-0.095	0.22	-9999	-0.58	66	66
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.026	0.093	-9999	-0.62	3	3
CNGB1	-0.001	0.063	-9999	-0.31	16	16
RDH5	-0.2	0.16	-9999	-0.31	264	264
SAG	0.002	0.016	-9999	-0.31	1	1
mol:Ca2+	0.014	0.096	-9999	-0.84	1	1
Na + (4 Units)	-0.023	0.083	-9999	-0.8	1	1
RGS9	-0.077	0.26	-9999	-0.83	44	44
GNB1/GNGT1	-0.003	0.026	-9999	-10000	0	0
GNAT1/GDP	-0.084	0.19	-9999	-0.51	66	66
GUCY2D	-0.011	0.12	-9999	-0.48	20	20
GNGT1	-0.005	0.041	-9999	-0.31	7	7
GUCY2F	0.001	0.003	-9999	-10000	0	0
GNB5	0.013	0	-9999	-10000	0	0
mol:GMP (4 units)	0.003	0.068	-9999	-0.5	3	3
mol:11-cis-retinal	-0.2	0.16	-9999	-0.31	264	264
mol:cGMP	-0.017	0.078	-9999	-0.5	9	9
GNB1	0.013	0	-9999	-10000	0	0
Rhodopsin	-0.13	0.099	-9999	-10000	0	0
SLC24A1	0.013	0	-9999	-10000	0	0
CNGA1	-0.001	0.1	-9999	-0.58	10	10
Metarhodopsin II	-0.053	0.16	-9999	-0.54	40	40
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.018	0.082	-9999	-0.53	9	9
RGS9BP	-0.042	0.21	-9999	-0.85	26	26
Metarhodopsin II/Transducin	0.01	0.016	-9999	-10000	0	0
GCAP Family/Ca ++	-0.005	0.048	-9999	-0.54	3	3
PDE6A/B	-0.012	0.048	-9999	-10000	0	0
mol:Pi	-0.095	0.22	-9999	-0.58	66	66
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.003	0.024	-9999	-10000	0	0
PDE6B	0.013	0	-9999	-10000	0	0
PDE6A	-0.009	0.078	-9999	-10000	0	0
PDE6G	-0.013	0.11	-9999	-0.85	3	3
RHO	0.006	0.017	-9999	-0.31	1	1
PDE6	-0.094	0.19	-9999	-0.5	68	68
GUCA1A	0.005	0.028	-9999	-0.31	3	3
GC2/GCAP Family	-0.005	0.048	-9999	-0.54	3	3
GUCA1C	0	0	-9999	-10000	0	0
GUCA1B	0.007	0.074	-9999	-0.85	3	3

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.021	0.005	-9999	-10000	0	0
SMARCC1	0.014	0.014	-9999	-10000	0	0
REL	-0.024	0.19	-9999	-0.85	20	20
HDAC7	-0.024	0.12	-9999	-0.57	9	9
JUN	-0.19	0.36	-9999	-0.85	93	93
EP300	0.013	0.001	-9999	-10000	0	0
KAT2B	0.012	0.003	-9999	-10000	0	0
KAT5	0.014	0.001	-9999	-10000	0	0
MAPK14	0.001	0.084	-9999	-0.67	6	6
FOXO1	0.012	0.001	-9999	-10000	0	0
T-DHT/AR	-0.037	0.13	-9999	-0.61	9	9
MAP2K6	-0.006	0.11	-9999	-0.78	7	7
BRM/BAF57	-0.001	0.003	-9999	-10000	0	0
MAP2K4	0.008	0.007	-9999	-10000	0	0
SMARCA2	0.009	0.007	-9999	-10000	0	0
PDE9A	0.011	0.057	-9999	-10000	0	0
NCOA2	-0.057	0.22	-9999	-0.85	30	30
CEBPA	0.006	0.085	-9999	-0.85	4	4
EHMT2	0.009	0.006	-9999	-10000	0	0
cell proliferation	-0.061	0.14	-9999	-0.47	11	11
NR0B1	-0.002	0.038	-9999	-0.31	6	6
EGR1	-0.18	0.36	-9999	-0.86	89	89
RXRs/9cRA	-0.13	0.06	-9999	-0.53	3	3
AR/RACK1/Src	-0.11	0.14	-9999	-0.61	9	9
AR/GR	-0.12	0.19	-9999	-0.35	122	122
GNB2L1	0.006	0.007	-9999	-10000	0	0
PKN1	0.012	0.003	-9999	-10000	0	0
RCHY1	0.013	0	-9999	-10000	0	0
epidermal growth factor receptor activity	-0.006	0.005	-9999	-10000	0	0
MAPK8	0.007	0.059	-9999	-0.66	3	3
T-DHT/AR/TIF2/CARM1	-0.11	0.2	-9999	-0.65	35	35
SRC	0.006	0.083	-9999	-0.5	9	9
NR3C1	0.013	0	-9999	-10000	0	0
KLK3	-0.39	0.57	-9999	-1.3	111	111
APPBP2	0.013	0.004	-9999	-10000	0	0
TRIM24	0.009	0.007	-9999	-10000	0	0
T-DHT/AR/TIP60	-0.046	0.12	-9999	-0.63	9	9
TMPRSS2	-0.056	0.31	-9999	-1.3	25	25
RXRG	-0.28	0.12	-9999	-0.32	359	359
mol:9cRA	-0.002	0.002	-9999	-10000	0	0
RXRA	0.012	0.001	-9999	-10000	0	0
RXRB	0.012	0.001	-9999	-10000	0	0
CARM1	0.006	0.007	-9999	-10000	0	0
NR2C2	0.004	0.085	-9999	-0.85	4	4
KLK2	-0.48	0.43	-9999	-0.84	235	235
AR	-0.15	0.2	-9999	-0.38	172	172
SENP1	0.012	0.002	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
MDM2	0.022	0.014	-9999	-10000	0	0
SRY	0.009	0.014	-9999	-10000	0	0
GATA2	0.012	0.016	-9999	-0.31	1	1
MYST2	0.014	0.002	-9999	-10000	0	0
HOXB13	-0.016	0.058	-9999	-0.32	13	13
T-DHT/AR/RACK1/Src	-0.069	0.12	-9999	-0.62	9	9
positive regulation of transcription	0.012	0.016	-9999	-0.31	1	1
DNAJA1	0.013	0.004	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.034	0.004	-9999	-10000	0	0
NCOA1	0.012	0.009	-9999	-10000	0	0
SPDEF	-0.026	0.1	-9999	-0.32	44	44
T-DHT/AR/TIF2	-0.043	0.13	-9999	-0.42	29	29
T-DHT/AR/Hsp90	-0.048	0.12	-9999	-0.63	9	9
GSK3B	0.009	0.006	-9999	-10000	0	0
NR2C1	0.015	0.003	-9999	-10000	0	0
mol:T-DHT	0.003	0.087	-9999	-0.54	9	9
SIRT1	0.013	0.001	-9999	-10000	0	0
ZMIZ2	0.022	0.015	-9999	-10000	0	0
POU2F1	0.031	0.02	-9999	-0.3	1	1
T-DHT/AR/DAX-1	-0.067	0.11	-9999	-0.63	9	9
CREBBP	0.012	0.003	-9999	-10000	0	0
SMARCE1	0.009	0.007	-9999	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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
LAT/GRAP2/SLP76/HPK1	-0.06	0.17	-9999	-0.57	37	37
MAP4K1	-0.02	0.13	-9999	-0.44	30	30
MAP3K8	0	0.1	-9999	-0.85	6	6
PRKCB	-0.023	0.11	-9999	-0.34	42	42
DBNL	0.013	0	-9999	-10000	0	0
CRKL	0.013	0	-9999	-10000	0	0
MAP3K1	0.011	0.11	-9999	-0.57	5	5
JUN	-0.1	0.24	-9999	-0.51	97	97
MAP3K7	0.011	0.11	-9999	-0.57	5	5
GRAP2	-0.046	0.22	-9999	-0.8	30	30
CRK	0.013	0	-9999	-10000	0	0
MAP2K4	0.018	0.11	-9999	-0.54	6	6
LAT	0.004	0.086	-9999	-0.74	5	5
LCP2	0.007	0.045	-9999	-0.31	8	8
MAPK8	0.009	0.092	-9999	-0.74	5	5
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.002	0.12	-9999	-0.38	28	28
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.056	0.16	-9999	-0.54	37	37

×

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	0.038	0.036	-9999	-10000	0	0
VDR	0.012	0.016	-9999	-0.31	1	1
FAM120B	0.013	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.057	0.1	-9999	-0.58	2	2
RXRs/LXRs/DNA/Oxysterols	-0.046	0.15	-9999	-0.45	47	47
MED1	0.013	0	-9999	-10000	0	0
mol:9cRA	0	0.017	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	0.025	0.073	-9999	-0.34	16	16
RXRs/NUR77	-0.27	0.26	-9999	-0.66	123	123
RXRs/PPAR	-0.053	0.062	-9999	-0.4	8	8
NCOR2	0.013	0	-9999	-10000	0	0
VDR/VDR/Vit D3	-0.001	0.011	-9999	-10000	0	0
RARs/VDR/DNA/Vit D3	-0.012	0.079	-9999	-0.51	10	10
RARA	0.013	0	-9999	-10000	0	0
NCOA1	0.013	0	-9999	-10000	0	0
VDR/VDR/DNA	0.012	0.016	-9999	-0.31	1	1
RARs/RARs/DNA/9cRA	-0.012	0.077	-9999	-0.5	10	10
RARG	0.013	0	-9999	-10000	0	0
RPS6KB1	0.054	0.03	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	0.025	0.073	-9999	-0.34	16	16
THRA	0.013	0	-9999	-10000	0	0
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	-0.001	0.011	-9999	-10000	0	0
RXRs/PPAR/9cRA/PGJ2/DNA	-0.12	0.081	-9999	-0.6	3	3
NR1H4	0	0.035	-9999	-0.31	5	5
RXRs/LXRs/DNA	-0.097	0.089	-9999	-0.59	3	3
NR1H2	0.015	0.012	-9999	-10000	0	0
NR1H3	0.015	0.014	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.1	0.067	-9999	-0.54	3	3
NR4A1	-0.24	0.39	-9999	-0.85	122	122
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.046	0.047	-9999	-0.32	3	3
RXRG	-0.28	0.12	-9999	-0.32	359	359
RXR alpha/CCPG	0	0.003	-9999	-10000	0	0
RXRA	0.015	0.012	-9999	-10000	0	0
RXRB	0.014	0.014	-9999	-10000	0	0
THRB	0	0.1	-9999	-0.85	6	6
PPARG	-0.001	0.1	-9999	-0.58	10	10
PPARD	0.013	0	-9999	-10000	0	0
TNF	-0.14	0.41	-9999	-1.3	47	47
mol:Oxysterols	0.001	0.016	-9999	-10000	0	0
cholesterol transport	-0.046	0.15	-9999	-0.45	47	47
PPARA	0.013	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	-0.008	0.13	-9999	-0.85	10	10
RXRs/NUR77/BCL2	-0.19	0.2	-9999	-0.46	139	139
SREBF1	-0.036	0.14	-9999	-0.63	2	2
RXRs/RXRs/DNA/9cRA	-0.12	0.081	-9999	-0.6	3	3
ABCA1	-0.035	0.14	-9999	-0.63	2	2
RARs/THRs	-0.019	0.094	-9999	-0.48	16	16
RXRs/FXR	-0.12	0.071	-9999	-0.57	3	3
BCL2	-0.042	0.21	-9999	-0.85	26	26

×

Integrins in angiogenesis

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.008	0.072	-9999	-0.66	5	5
alphaV beta3 Integrin	-0.019	0.11	-9999	-0.61	13	13
PTK2	0.013	0.16	-9999	-0.55	15	15
IGF1R	0.013	0	-9999	-10000	0	0
PI4KB	0.013	0	-9999	-10000	0	0
MFGE8	-0.028	0.11	-9999	-0.31	51	51
SRC	0.012	0.016	-9999	-0.31	1	1
CDKN1B	-0.07	0.19	-9999	-0.63	41	41
VEGFA	0.009	0.06	-9999	-0.85	2	2
ILK	-0.07	0.19	-9999	-0.63	41	41
ROCK1	0.013	0	-9999	-10000	0	0
AKT1	-0.065	0.18	-9999	-0.59	41	41
PTK2B	0.018	0.12	-9999	-0.54	17	17
alphaV/beta3 Integrin/JAM-A	-0.067	0.17	-9999	-0.5	53	53
CBL	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.02	0.11	-9999	-0.61	13	13
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.17	0.27	-9999	-0.56	122	122
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0	0.12	-9999	-0.55	3	3
alphaV/beta3 Integrin/Syndecan-1	-0.02	0.11	-9999	-0.61	13	13
PI4KA	0.013	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.23	0.26	-9999	-0.58	129	129
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0.011	0.043	-9999	-0.85	1	1
alphaV/beta3 Integrin/Osteopontin	-0.073	0.17	-9999	-0.6	33	33
RPS6KB1	-0.2	0.25	-9999	-0.6	88	88
TLN1	0.013	0	-9999	-10000	0	0
MAPK3	-0.096	0.16	-9999	-0.8	13	13
GPR124	0.013	0	-9999	-10000	0	0
MAPK1	-0.096	0.16	-9999	-0.8	13	13
PXN	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.037	0.16	-9999	-0.66	23	23
cell adhesion	-0.031	0.1	-9999	-0.56	13	13
ANGPTL3	0.006	0.017	-9999	-0.31	1	1
VEGFR2 homodimer/VEGFA homodimer/Src	-0.007	0.063	-9999	-0.57	5	5
IGF-1R heterotetramer	0.013	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	0.011	0.043	-9999	-0.85	1	1
ITGB3	-0.014	0.15	-9999	-0.85	13	13
IGF1	-0.18	0.36	-9999	-0.82	94	94
RAC1	0.013	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.019	0.11	-9999	-0.6	13	13
apoptosis	0.011	0.042	-9999	-0.85	1	1
CD47	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.019	0.11	-9999	-0.61	13	13
VCL	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.035	0.13	-9999	-0.63	16	16
CSF1	0.003	0.095	-9999	-0.85	5	5
PIK3C2A	-0.07	0.19	-9999	-0.63	41	41
PI4 Kinase/Pyk2	-0.06	0.15	-9999	-0.82	3	3
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.024	0.12	-9999	-0.58	17	17
FAK1/Vinculin	0.022	0.13	-9999	-0.51	6	6
alphaV beta3/Integrin/ppsTEM5	-0.019	0.11	-9999	-0.61	13	13
RHOA	0.013	0	-9999	-10000	0	0
VTN	-0.078	0.26	-9999	-0.79	46	46
BCAR1	0.013	0	-9999	-10000	0	0
FGF2	0.013	0	-9999	-10000	0	0
F11R	0.024	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Lactadherin	-0.039	0.12	-9999	-0.61	13	13
alphaV/beta3 Integrin/TGFBR2	-0.021	0.11	-9999	-0.61	14	14
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.008	0.062	-9999	-0.52	6	6
HSP90AA1	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.018	0.1	-9999	-0.56	13	13
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.22	0.15	-9999	-0.31	295	295
alphaV/beta3 Integrin/Pyk2	-0.022	0.11	-9999	-0.54	17	17
SDC1	0.011	0.028	-9999	-0.31	3	3
VAV3	0.029	0.081	-9999	-0.48	10	10
PTPN11	0.013	0	-9999	-10000	0	0
IRS1	-0.078	0.26	-9999	-0.85	43	43
FAK1/Paxillin	0.022	0.13	-9999	-0.51	6	6
cell migration	0.032	0.12	-9999	-0.46	6	6
ITGAV	0.011	0.043	-9999	-0.85	1	1
PI3K	-0.061	0.16	-9999	-0.46	53	53
SPP1	-0.083	0.21	-9999	-0.44	88	88
KDR	0.007	0.074	-9999	-0.85	3	3
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.011	0.043	-9999	-0.85	1	1
COL4A3	-0.014	0.15	-9999	-0.85	13	13
angiogenesis	-0.087	0.19	-9999	-0.62	31	31
Rac1/GTP	-0.011	0.068	-9999	-0.44	10	10
EDIL3	-0.017	0.12	-9999	-0.38	31	31
cell proliferation	-0.021	0.11	-9999	-0.6	14	14

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.045	0.15	-9999	-0.54	33	33
NF kappa B1 p50/RelA/I kappa B alpha	-0.022	0.041	-9999	-10000	0	0
AP1	-0.26	0.38	-9999	-0.73	144	144
mol:PIP3	-0.044	0.14	-9999	-0.47	32	32
AKT1	-0.028	0.095	-9999	-0.56	3	3
PTK2B	0.001	0.084	-9999	-0.27	33	33
RHOA	0.031	0.046	-9999	-0.27	1	1
PIK3CB	0.013	0.001	-9999	-10000	0	0
mol:Ca2+	0.006	0.073	-9999	-10000	0	0
MAGI3	0.011	0.043	-9999	-0.85	1	1
RELA	0.013	0	-9999	-10000	0	0
apoptosis	-0.015	0.14	-9999	-0.45	33	33
HRAS/GDP	-0.001	0.015	-9999	-0.21	2	2
positive regulation of microtubule depolymerization	0.009	0.086	-9999	-0.34	8	8
NF kappa B1 p50/RelA	-0.048	0.12	-9999	-0.54	7	7
endothelial cell migration	-0.027	0.2	-9999	-0.64	34	34
ADCY4	-0.014	0.19	-9999	-0.63	33	33
ADCY5	-0.048	0.21	-9999	-0.65	36	36
ADCY6	-0.014	0.19	-9999	-0.63	33	33
ADCY7	-0.014	0.19	-9999	-0.63	33	33
ADCY1	-0.017	0.2	-9999	-0.64	33	33
ADCY2	-0.038	0.21	-9999	-0.67	34	34
ADCY3	-0.014	0.19	-9999	-0.63	33	33
ADCY8	-0.056	0.19	-9999	-0.66	34	34
ADCY9	-0.014	0.19	-9999	-0.63	33	33
GSK3B	0.009	0.08	-9999	-0.3	7	7
arachidonic acid secretion	-0.007	0.18	-9999	-0.54	39	39
GNG2	0.013	0.001	-9999	-10000	0	0
TRIP6	0.026	0.008	-9999	-10000	0	0
GNAO1	-0.04	0.2	-9999	-0.61	44	44
HRAS	0.012	0.023	-9999	-0.31	2	2
NFKBIA	0.012	0.076	-9999	-10000	0	0
GAB1	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.032	0.097	-9999	-0.98	4	4
JUN	-0.18	0.36	-9999	-0.85	93	93
LPA/LPA2/NHERF2	-0.001	0.006	-9999	-10000	0	0
TIAM1	-0.042	0.12	-9999	-1.2	4	4
PIK3R1	0.013	0.001	-9999	-10000	0	0
mol:IP3	0.006	0.074	-9999	-10000	0	0
PLCB3	0.03	0.007	-9999	-10000	0	0
FOS	-0.21	0.38	-9999	-0.85	106	106
positive regulation of mitosis	-0.007	0.18	-9999	-0.54	39	39
LPA/LPA1-2-3	-0.052	0.16	-9999	-0.55	33	33
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.013	0	-9999	-10000	0	0
stress fiber formation	0.004	0.11	-9999	-0.36	33	33
GNAZ	-0.022	0.17	-9999	-0.59	34	34
EGFR/PI3K-beta/Gab1	-0.046	0.14	-9999	-0.51	28	28
positive regulation of dendritic cell cytokine production	-0.051	0.15	-9999	-0.55	33	33
LPA/LPA2/MAGI-3	-0.002	0.031	-9999	-0.62	1	1
ARHGEF1	-0.002	0.15	-9999	-0.5	33	33
GNAI2	-0.022	0.17	-9999	-0.59	34	34
GNAI3	-0.022	0.17	-9999	-0.59	34	34
GNAI1	-0.022	0.17	-9999	-0.59	34	34
LPA/LPA3	-0.01	0.044	-9999	-0.27	1	1
LPA/LPA2	-0.001	0.008	-9999	-10000	0	0
LPA/LPA1	-0.057	0.19	-9999	-0.68	34	34
HB-EGF/EGFR	-0.057	0.18	-9999	-0.57	39	39
HBEGF	-0.062	0.2	-9999	-0.64	36	36
mol:DAG	0.006	0.074	-9999	-10000	0	0
cAMP biosynthetic process	-0.027	0.2	-9999	-0.58	43	43
NFKB1	0.013	0	-9999	-10000	0	0
SRC	0.012	0.016	-9999	-0.31	1	1
GNB1	0.013	0.001	-9999	-10000	0	0
LYN	0.012	0.076	-9999	-10000	0	0
GNAQ	0.019	0.029	-9999	-10000	0	0
LPAR2	0.013	0	-9999	-10000	0	0
LPAR3	-0.004	0.067	-9999	-0.31	18	18
LPAR1	-0.054	0.24	-9999	-0.86	33	33
IL8	-0.13	0.2	-9999	-0.48	52	52
PTK2	-0.011	0.16	-9999	-0.52	33	33
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.016	0.14	-9999	-0.46	33	33
EGFR	0.002	0.095	-9999	-0.85	5	5
PLCG1	-0.013	0.084	-9999	-0.29	11	11
PLD2	-0.011	0.16	-9999	-0.52	33	33
G12/G13	-0.045	0.15	-9999	-0.54	33	33
PI3K-beta	-0.033	0.11	-9999	-0.67	3	3
cell migration	-0.016	0.058	-9999	-0.26	7	7
SLC9A3R2	0.013	0	-9999	-10000	0	0
PXN	0.003	0.11	-9999	-0.36	33	33
HRAS/GTP	-0.019	0.19	-9999	-0.6	33	33
RAC1	0.013	0	-9999	-10000	0	0
MMP9	-0.084	0.25	-9999	-0.59	66	66
PRKCE	0.007	0.074	-9999	-0.85	3	3
PRKCD	0.014	0.071	-9999	-10000	0	0
Gi(beta/gamma)	-0.008	0.18	-9999	-0.59	33	33
mol:LPA	0.003	0.016	-9999	-0.22	1	1
TRIP6/p130 Cas/FAK1/Paxillin	-0.031	0.13	-9999	-0.46	33	33
MAPKKK cascade	-0.007	0.18	-9999	-0.54	39	39
contractile ring contraction involved in cytokinesis	0.031	0.046	-9999	-0.27	1	1
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.086	0.2	-9999	-0.45	92	92
GNA15	0.009	0.055	-9999	-0.25	9	9
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
MAPT	0.009	0.088	-9999	-0.36	7	7
GNA11	0.014	0.054	-9999	-0.44	4	4
Rac1/GTP	-0.033	0.1	-9999	-1.1	4	4
MMP2	-0.027	0.2	-9999	-0.64	34	34

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.036	0.12	-10000	0	-0.52	22	22
ER alpha/Gai/GDP/Gbeta gamma	0.007	0.15	-10000	0	-0.57	19	19
AKT1	-0.011	0.2	-10000	0	-0.87	20	20
PIK3CA	0.011	0.043	-10000	0	-0.85	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.012	0.2	-10000	0	-0.88	20	20
mol:Ca2+	-0.097	0.23	-10000	0	-0.5	94	94
IGF1R	0.013	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	-0.064	0.18	-10000	0	-0.6	37	37
SHC1	0.013	0	-10000	0	-10000	0	0
apoptosis	0.009	0.19	0.82	20	-10000	0	20
RhoA/GTP	-0.027	0.092	-10000	0	-0.43	19	19
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.035	0.13	-10000	0	-0.61	19	19
regulation of stress fiber formation	-0.02	0.1	0.44	2	-10000	0	2
E2/ERA-ERB (dimer)	-0.043	0.14	-10000	0	-0.6	22	22
KRAS	0.013	0	-10000	0	-10000	0	0
G13/GTP	-0.035	0.12	-10000	0	-0.53	19	19
pseudopodium formation	0.02	0.1	-10000	0	-0.44	2	2
E2/ER alpha (dimer)/PELP1	-0.038	0.13	-10000	0	-0.58	19	19
GRB2	0.013	0	-10000	0	-10000	0	0
GNG2	0.013	0	-10000	0	-10000	0	0
GNAO1	-0.015	0.15	-10000	0	-0.72	16	16
HRAS	0.012	0.023	-10000	0	-0.31	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.014	0.15	-10000	0	-0.62	19	19
E2/ER beta (dimer)	-0.007	0.066	-10000	0	-0.67	4	4
mol:GDP	-0.037	0.13	-10000	0	-0.58	22	22
mol:NADP	0.014	0.15	-10000	0	-0.62	19	19
PIK3R1	0.013	0	-10000	0	-10000	0	0
mol:IP3	-0.1	0.24	-10000	0	-0.52	94	94
IGF-1R heterotetramer	0.013	0	-10000	0	-10000	0	0
PLCB1	-0.11	0.24	-10000	0	-0.54	94	94
PLCB2	-0.11	0.24	-10000	0	-0.55	92	92
IGF1	-0.18	0.36	-10000	0	-0.82	94	94
mol:L-citrulline	0.014	0.15	-10000	0	-0.62	19	19
RHOA	0.013	0	-10000	0	-10000	0	0
Gai/GDP	-0.024	0.14	-10000	0	-0.82	12	12
JNK cascade	-0.006	0.065	-10000	0	-0.66	4	4
BCAR1	0.013	0	-10000	0	-10000	0	0
ESR2	0.005	0.085	-10000	0	-0.85	4	4
GNAQ	0.013	0	-10000	0	-10000	0	0
ESR1	-0.049	0.2	-10000	0	-0.85	19	19
Gq family/GDP/Gbeta gamma	-0.049	0.16	-10000	0	-0.49	14	14
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.02	0.082	-10000	0	-0.37	4	4
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.035	0.13	-10000	0	-0.61	19	19
GNAZ	0.013	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)	-0.045	0.15	-10000	0	-0.67	19	19
STRN	-0.027	0.18	-10000	0	-0.85	19	19
GNAL	-0.09	0.28	-10000	0	-0.85	49	49
PELP1	0.013	0	-10000	0	-10000	0	0
MAPK11	0.014	0.059	-10000	0	-0.58	4	4
GNAI2	0.013	0	-10000	0	-10000	0	0
GNAI3	0.013	0	-10000	0	-10000	0	0
GNAI1	0.013	0	-10000	0	-10000	0	0
HBEGF	-0.002	0.16	-10000	0	-0.67	13	13
cAMP biosynthetic process	-0.091	0.2	-10000	0	-0.51	67	67
SRC	0.015	0.14	-10000	0	-0.53	19	19
PI3K	-0.002	0.032	-10000	0	-0.66	1	1
GNB1	0.013	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.031	0.12	-10000	0	-0.52	19	19
SOS1	0.013	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.1	0.18	-10000	0	-0.54	31	31
Gs family/GTP	-0.093	0.2	-10000	0	-0.52	67	67
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.001	0.01	-10000	0	-10000	0	0
vasodilation	0.015	0.14	-10000	0	-0.59	19	19
mol:DAG	-0.1	0.24	-10000	0	-0.52	94	94
Gs family/GDP/Gbeta gamma	-0.073	0.16	-10000	0	-0.52	23	23
MSN	0.019	0.11	-10000	0	-0.48	2	2
Gq family/GTP	-0.14	0.24	-10000	0	-0.57	95	95
mol:PI-3-4-5-P3	-0.01	0.19	-10000	0	-0.83	20	20
NRAS	0.013	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.015	0.14	0.59	19	-10000	0	19
GRB2/SOS1	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.034	0.12	-10000	0	-0.54	22	22
NOS3	0.012	0.16	-10000	0	-0.66	19	19
GNA11	0.005	0.085	-10000	0	-0.85	4	4
MAPKKK cascade	0	0.19	-10000	0	-0.56	37	37
E2/ER alpha (dimer)/PELP1/Src	-0.038	0.14	-10000	0	-0.65	19	19
ruffle organization	0.02	0.1	-10000	0	-0.44	2	2
ROCK2	0.01	0.12	-10000	0	-0.44	10	10
GNA14	-0.18	0.36	-10000	0	-0.85	92	92
GNA15	-0.012	0.094	-10000	0	-0.33	30	30
GNA13	0.013	0	-10000	0	-10000	0	0
MMP9	-0.027	0.2	-10000	0	-0.56	38	38
MMP2	0.018	0.14	-10000	0	-0.72	8	8

×

IL27-mediated signaling events

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
TGFB1	0.011	0.04	-10000	0	-10000	0	0
CD4-positive alpha-beta T cell lineage commitment	0	0.001	-10000	0	-10000	0	0
cytokine production during immune response	0.058	0.14	0.43	19	-10000	0	19
IL27/IL27R/JAK1	-0.11	0.19	-10000	0	-0.61	33	33
TBX21	-0.084	0.22	-10000	0	-0.65	29	29
IL12B	-0.005	0.093	-10000	0	-0.53	10	10
IL12A	-0.056	0.2	-10000	0	-0.64	42	42
IL6ST	-0.093	0.28	-10000	0	-0.86	49	49
IL27RA/JAK1	0.013	0.026	-10000	0	-10000	0	0
IL27	0.002	0.037	-10000	0	-0.32	5	5
TYK2	0.012	0.006	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.07	0.16	-10000	0	-0.52	1	1
T-helper 2 cell differentiation	0.058	0.14	0.43	19	-10000	0	19
T cell proliferation during immune response	0.058	0.14	0.43	19	-10000	0	19
MAPKKK cascade	-0.058	0.14	-10000	0	-0.43	19	19
STAT3	0.013	0	-10000	0	-10000	0	0
STAT2	0.013	0	-10000	0	-10000	0	0
STAT1	0.006	0.048	-10000	0	-0.31	9	9
IL12RB1	-0.022	0.12	-10000	0	-0.36	37	37
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.083	0.21	-10000	0	-0.65	23	23
IL27/IL27R/JAK2/TYK2	-0.059	0.14	-10000	0	-0.44	18	18
positive regulation of T cell mediated cytotoxicity	-0.058	0.14	-10000	0	-0.43	19	19
STAT1 (dimer)	-0.11	0.24	0.52	14	-0.81	11	25
JAK2	0.014	0.007	-10000	0	-10000	0	0
JAK1	0.013	0.002	-10000	0	-10000	0	0
STAT2 (dimer)	-0.048	0.13	-10000	0	-0.52	6	6
T cell proliferation	-0.16	0.24	-10000	0	-0.54	94	94
IL12/IL12R/TYK2/JAK2	-0.054	0.16	-10000	0	-0.7	11	11
IL17A	-0.071	0.16	-10000	0	-0.52	1	1
mast cell activation	0.058	0.14	0.43	19	-10000	0	19
IFNG	-0.019	0.049	-10000	0	-0.13	56	56
T cell differentiation	-0.005	0.008	-10000	0	-0.022	54	54
STAT3 (dimer)	-0.048	0.13	-10000	0	-0.52	6	6
STAT5A (dimer)	-0.048	0.13	-10000	0	-0.52	6	6
STAT4 (dimer)	-0.07	0.16	-10000	0	-0.52	19	19
STAT4	-0.031	0.15	-10000	0	-0.45	39	39
T cell activation	-0.011	0.005	-10000	0	-10000	0	0
IL27R/JAK2/TYK2	-0.053	0.17	-10000	0	-0.59	9	9
GATA3	-0.054	0.36	-10000	0	-1.5	23	23
IL18	-0.026	0.12	-10000	0	-0.3	50	50
positive regulation of mast cell cytokine production	-0.047	0.13	-10000	0	-0.51	6	6
IL27/EBI3	-0.098	0.12	-10000	0	-0.44	6	6
IL27RA	0.004	0.027	-10000	0	-10000	0	0
IL6	-0.19	0.35	-10000	0	-0.85	88	88
STAT5A	0.013	0	-10000	0	-10000	0	0
monocyte differentiation	-0.001	0.003	-10000	0	-10000	0	0
IL2	0.002	0.013	-10000	0	-10000	0	0
IL1B	-0.044	0.18	-10000	0	-0.67	32	32
EBI3	-0.15	0.17	-10000	0	-0.34	33	33
TNF	-0.07	0.22	-10000	0	-0.62	53	53

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.013	0	-9999	-10000	0	0
mol:Halofuginone	0.005	0.002	-9999	-10000	0	0
ITGA1	0	0.1	-9999	-0.85	6	6
CDKN1A	-0.015	0.092	-9999	-0.26	2	2
PRL-3/alpha Tubulin	-0.013	0.05	-9999	-10000	0	0
mol:Ca2+	-0.017	0.11	-9999	-0.39	21	21
AGT	-0.021	0.14	-9999	-0.46	29	29
CCNA2	-0.07	0.22	-9999	-0.48	89	89
TUBA1B	0.013	0	-9999	-10000	0	0
EGR1	-0.12	0.28	-9999	-0.65	89	89
CDK2/Cyclin E1	-0.033	0.061	-9999	-10000	0	0
MAPK3	0.009	0.056	-9999	-10000	0	0
PRL-2 /Rab GGTase beta	0	0	-9999	-10000	0	0
MAPK1	0.009	0.056	-9999	-10000	0	0
PTP4A1	-0.079	0.22	-9999	-0.51	89	89
PTP4A3	-0.008	0.081	-9999	-0.31	27	27
PTP4A2	0.013	0	-9999	-10000	0	0
ITGB1	0.009	0.056	-9999	-10000	0	0
SRC	0.012	0.016	-9999	-0.31	1	1
RAC1	-0.017	0.094	-9999	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0	0	-9999	-10000	0	0
PRL-1/ATF-5	-0.075	0.21	-9999	-0.48	89	89
RABGGTA	0.013	0	-9999	-10000	0	0
BCAR1	0.01	0.036	-9999	-10000	0	0
RHOC	-0.017	0.094	-9999	-10000	0	0
RHOA	-0.017	0.094	-9999	-0.26	9	9
cell motility	-0.016	0.1	-9999	-0.27	9	9
PRL-1/alpha Tubulin	-0.068	0.21	-9999	-0.47	89	89
PRL-3/alpha1 Integrin	-0.023	0.097	-9999	-0.71	6	6
ROCK1	-0.016	0.1	-9999	-0.27	9	9
RABGGTB	0.013	0	-9999	-10000	0	0
CDK2	0.013	0	-9999	-10000	0	0
mitosis	-0.078	0.22	-9999	-0.5	89	89
ATF5	0	0.065	-9999	-0.31	17	17

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.021	0.005	-9999	-10000	0	0
RAS family/GTP	-0.045	0.11	-9999	-0.4	19	19
NFATC4	-0.003	0.12	-9999	-0.58	2	2
ERBB2IP	0.013	0.003	-9999	-10000	0	0
HSP90 (dimer)	0.013	0	-9999	-10000	0	0
mammary gland morphogenesis	-0.05	0.14	-9999	-0.42	48	48
JUN	0.005	0.094	-9999	-0.27	7	7
HRAS	0.011	0.023	-9999	-0.31	2	2
DOCK7	-0.017	0.14	-9999	-0.42	18	18
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.061	0.17	-9999	-0.51	48	48
AKT1	0.012	0.003	-9999	-10000	0	0
BAD	0.021	0.003	-9999	-10000	0	0
MAPK10	-0.023	0.063	-9999	-0.29	1	1
mol:GTP	-0.001	0.002	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.03	0.16	-9999	-0.46	48	48
RAF1	-0.006	0.13	-9999	-0.41	19	19
ErbB2/ErbB3/neuregulin 2	-0.079	0.19	-9999	-0.54	59	59
STAT3	0	0.003	-9999	-10000	0	0
cell migration	0.023	0.08	-9999	-0.28	2	2
mol:PI-3-4-5-P3	0	0.002	-9999	-10000	0	0
cell proliferation	-0.13	0.33	-9999	-0.68	97	97
FOS	-0.11	0.28	-9999	-0.52	124	124
NRAS	0.013	0.001	-9999	-10000	0	0
mol:Ca2+	-0.05	0.14	-9999	-0.42	48	48
MAPK3	-0.086	0.26	-9999	-0.51	94	94
MAPK1	-0.086	0.26	-9999	-0.51	94	94
JAK2	-0.017	0.14	-9999	-0.41	22	22
NF2	-0.002	0.006	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.022	0.14	-9999	-0.39	48	48
NRG1	-0.075	0.26	-9999	-0.83	42	42
GRB2/SOS1	0	0	-9999	-10000	0	0
MAPK8	-0.01	0.13	-9999	-0.35	50	50
MAPK9	-0.023	0.063	-9999	-0.29	1	1
ERBB2	0	0	-9999	-10000	0	0
ERBB3	-0.011	0.13	-9999	-0.76	11	11
SHC1	0.012	0.003	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
apoptosis	0.003	0.011	-9999	-10000	0	0
STAT3 (dimer)	0	0.003	-9999	-10000	0	0
RNF41	0.027	0.008	-9999	-10000	0	0
FRAP1	0.01	0.003	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.033	0.09	-9999	-0.44	1	1
ErbB2/ErbB2/HSP90 (dimer)	0	0	-9999	-10000	0	0
CHRNA1	-0.058	0.2	-9999	-0.46	26	26
myelination	0.006	0.12	-9999	-0.53	2	2
PPP3CB	-0.015	0.13	-9999	-0.61	1	1
KRAS	0.013	0.001	-9999	-10000	0	0
RAC1-CDC42/GDP	-0.039	0.11	-9999	-0.92	1	1
NRG2	-0.095	0.28	-9999	-0.82	53	53
mol:GDP	-0.02	0.14	-9999	-0.38	48	48
SOS1	0.013	0.001	-9999	-10000	0	0
MAP2K2	-0.009	0.14	-9999	-0.42	19	19
SRC	0.012	0.016	-9999	-0.31	1	1
mol:cAMP	-0.001	0.002	-9999	-10000	0	0
PTPN11	-0.017	0.14	-9999	-0.4	30	30
MAP2K1	-0.079	0.23	-9999	-0.62	24	24
heart morphogenesis	-0.05	0.14	-9999	-0.42	48	48
RAS family/GDP	-0.039	0.11	-9999	-0.68	2	2
GRB2	0.013	0.001	-9999	-10000	0	0
PRKACA	-0.003	0.009	-9999	-10000	0	0
CHRNE	0.011	0.032	-9999	-0.13	11	11
HSP90AA1	0.013	0	-9999	-10000	0	0
activation of caspase activity	-0.012	0.003	-9999	-10000	0	0
nervous system development	-0.05	0.14	-9999	-0.42	48	48
CDC42	0.013	0	-9999	-10000	0	0

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.013	0	-10000	0	-10000	0	0
Jak2/Leptin Receptor	-0.016	0.094	0.21	4	-0.38	10	14
PTP1B/AKT1	-0.002	0.064	-10000	0	-0.39	2	2
FYN	0.013	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.011	0.071	-10000	0	-0.38	3	3
EGFR	0.001	0.096	-10000	0	-0.86	5	5
EGF/EGFR	-0.084	0.18	-10000	0	-0.52	60	60
CSF1	0.003	0.095	-10000	0	-0.85	5	5
AKT1	0.013	0.001	-10000	0	-10000	0	0
INSR	0.013	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.099	0.12	-10000	0	-0.45	23	23
Insulin Receptor/Insulin	-0.013	0.042	-10000	0	-10000	0	0
HCK	-0.008	0.08	-10000	0	-0.31	26	26
CRK	0.013	0	-10000	0	-10000	0	0
TYK2	-0.002	0.067	-10000	0	-0.4	2	2
EGF	-0.11	0.3	-10000	0	-0.8	61	61
YES1	0.013	0	-10000	0	-10000	0	0
CAV1	-0.017	0.1	-10000	0	-0.48	4	4
TXN	0.011	0.017	-10000	0	-0.32	1	1
PTP1B/IRS1/GRB2	-0.067	0.16	-10000	0	-0.5	45	45
cell migration	0.011	0.071	0.38	3	-10000	0	3
STAT3	0.013	0.001	-10000	0	-10000	0	0
PRLR	-0.042	0.19	-10000	0	-0.58	38	38
ITGA2B	-0.089	0.28	-10000	0	-0.85	48	48
CSF1R	0.007	0.056	-10000	0	-0.4	6	6
Prolactin Receptor/Prolactin	-0.037	0.15	-10000	0	-0.67	19	19
FGR	0.01	0.032	-10000	0	-0.31	4	4
PTP1B/p130 Cas	-0.003	0.066	-10000	0	-0.4	2	2
Crk/p130 Cas	-0.016	0.049	-10000	0	-0.38	2	2
DOK1	0.008	0.062	-10000	0	-0.36	2	2
JAK2	-0.007	0.084	-10000	0	-0.37	9	9
Jak2/Leptin Receptor/Leptin	-0.069	0.16	-10000	0	-0.61	32	32
PIK3R1	0.013	0	-10000	0	-10000	0	0
PTPN1	-0.011	0.071	-10000	0	-0.38	3	3
LYN	0.013	0	-10000	0	-10000	0	0
CDH2	-0.19	0.21	-10000	0	-0.35	227	227
SRC	0.012	0.03	-10000	0	-10000	0	0
ITGB3	-0.016	0.15	-10000	0	-0.85	13	13
CAT1/PTP1B	-0.091	0.15	-10000	0	-0.39	47	47
CAPN1	0.013	0.003	-10000	0	-10000	0	0
CSK	0.013	0	-10000	0	-10000	0	0
PI3K	-0.014	0.043	-10000	0	-0.62	1	1
mol:H2O2	0	0.004	-10000	0	-10000	0	0
STAT3 (dimer)	-0.069	0.18	-10000	0	-0.65	32	32
negative regulation of transcription	-0.006	0.083	-10000	0	-0.36	9	9
FCGR2A	-0.008	0.087	-10000	0	-0.34	25	25
FER	0.008	0.061	-10000	0	-0.86	2	2
alphaIIb/beta3 Integrin	-0.095	0.25	-10000	0	-0.72	55	55
BLK	-0.26	0.39	-10000	0	-0.78	143	143
Insulin Receptor/Insulin/Shc	0	0	-10000	0	-10000	0	0
RHOA	0.013	0.003	-10000	0	-10000	0	0
LEPR	0.004	0.087	-10000	0	-0.84	4	4
BCAR1	0.013	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.013	0	-10000	0	-10000	0	0
mol:NADPH	0	0.004	-10000	0	-10000	0	0
TRPV6	-0.12	0.19	-10000	0	-0.5	39	39
PRL	0.001	0.017	-10000	0	-0.31	1	1
SOCS3	-0.1	0.41	-10000	0	-1.5	32	32
SPRY2	0.012	0.017	-10000	0	-0.31	1	1
Insulin Receptor/Insulin/IRS1	-0.061	0.18	-10000	0	-0.58	43	43
CSF1/CSF1R	-0.025	0.078	-10000	0	-0.47	8	8
Ras protein signal transduction	0.02	0.023	-10000	0	-10000	0	0
IRS1	-0.078	0.26	-10000	0	-0.85	43	43
INS	0	0.001	-10000	0	-10000	0	0
LEP	-0.009	0.069	-10000	0	-0.31	20	20
STAT5B	-0.004	0.069	-10000	0	-0.29	5	5
STAT5A	-0.004	0.069	-10000	0	-0.29	5	5
GRB2	0.013	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.003	0.066	-10000	0	-0.4	2	2
CSN2	-0.006	0.053	-10000	0	-10000	0	0
PIK3CA	0.011	0.043	-10000	0	-0.85	1	1
LAT	0.001	0.071	-10000	0	-0.55	5	5
YBX1	0.021	0.002	-10000	0	-10000	0	0
LCK	-0.009	0.11	-10000	0	-0.45	20	20
SHC1	0.013	0	-10000	0	-10000	0	0
NOX4	-0.13	0.16	-10000	0	-0.31	176	176

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.013	0.21	-10000	0	-0.94	16	16
NCK1/PAK1/Dok-R	-0.027	0.086	-10000	0	-0.42	17	17
NCK1/Dok-R	-0.062	0.22	-10000	0	-1.1	16	16
PIK3CA	0.011	0.043	-10000	0	-0.85	1	1
mol:beta2-estradiol	-0.004	0.046	0.25	12	-10000	0	12
RELA	0.013	0	-10000	0	-10000	0	0
SHC1	0.013	0.001	-10000	0	-10000	0	0
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	-0.008	0.062	-10000	0	-0.33	6	6
TNIP2	0.013	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.054	0.2	-10000	0	-1	16	16
FN1	-0.22	0.15	-10000	0	-0.31	295	295
PLD2	0.007	0.25	-10000	0	-1.2	16	16
PTPN11	0.013	0	-10000	0	-10000	0	0
GRB14	-0.019	0.16	-10000	0	-0.85	15	15
ELK1	0.021	0.22	-10000	0	-1	16	16
GRB7	-0.037	0.12	-10000	0	-0.31	63	63
PAK1	0.013	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.099	0.22	-10000	0	-1.2	16	16
CDKN1A	-0.011	0.17	-10000	0	-0.63	16	16
ITGA5	0.013	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.062	0.22	-10000	0	-1.1	16	16
CRK	0.013	0	-10000	0	-10000	0	0
mol:NO	0.028	0.16	-10000	0	-0.68	16	16
PLG	-0.002	0.25	-10000	0	-1.2	16	16
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.01	0.2	-10000	0	-0.9	16	16
GRB2	0.013	0	-10000	0	-10000	0	0
PIK3R1	0.013	0.002	-10000	0	-10000	0	0
ANGPT2	-0.11	0.23	-10000	0	-0.8	18	18
BMX	-0.006	0.26	-10000	0	-1.2	18	18
ANGPT1	-0.035	0.28	-10000	0	-1.5	14	14
tube development	-0.017	0.18	-10000	0	-0.72	16	16
ANGPT4	-0.064	0.24	-10000	0	-0.75	42	42
response to hypoxia	0	0.016	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.018	0.27	-10000	0	-1.2	16	16
alpha5/beta1 Integrin	0	0	-10000	0	-10000	0	0
FGF2	0.012	0.001	-10000	0	-10000	0	0
STAT5A (dimer)	-0.019	0.2	-10000	0	-0.82	16	16
mol:L-citrulline	0.028	0.16	-10000	0	-0.68	16	16
AGTR1	-0.33	0.42	-10000	0	-0.85	164	164
MAPK14	-0.006	0.24	-10000	0	-1.2	16	16
Tie2/SHP2	-0.018	0.095	-10000	0	-1.2	2	2
TEK	0.023	0.12	-10000	0	-1.4	2	2
RPS6KB1	0.013	0.2	-10000	0	-0.9	16	16
Angiotensin II/AT1	-0.26	0.33	-10000	0	-0.66	163	163
Tie2/Ang1/GRB2	0.001	0.25	-10000	0	-1.2	16	16
MAPK3	0.017	0.23	-10000	0	-1.1	16	16
MAPK1	0.017	0.23	-10000	0	-1.1	16	16
Tie2/Ang1/GRB7	-0.021	0.26	-10000	0	-1.2	16	16
NFKB1	0.013	0	-10000	0	-10000	0	0
MAPK8	0.003	0.25	-10000	0	-1.1	17	17
PI3K	-0.001	0.24	-10000	0	-1.1	16	16
FES	-0.006	0.24	-10000	0	-1.2	16	16
Crk/Dok-R	-0.062	0.22	-10000	0	-1.1	16	16
Tie2/Ang1/ABIN2	0.001	0.25	-10000	0	-1.2	16	16
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.017	0.19	-10000	0	-0.83	16	16
STAT5A	0.013	0.001	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.013	0.2	-10000	0	-0.9	16	16
Tie2/Ang2	-0.037	0.23	-10000	0	-0.99	16	16
Tie2/Ang1	-0.004	0.26	-10000	0	-1.3	16	16
FOXO1	0.023	0.19	-10000	0	-0.83	16	16
ELF1	0.02	0.043	-10000	0	-0.84	1	1
ELF2	0.003	0.24	-10000	0	-1.1	16	16
mol:Choline	0.009	0.24	-10000	0	-1.1	16	16
cell migration	-0.023	0.054	-10000	0	-0.25	2	2
FYN	-0.022	0.2	-10000	0	-0.82	16	16
DOK2	0.001	0.078	-10000	0	-0.4	12	12
negative regulation of cell cycle	-0.007	0.16	-10000	0	-0.57	16	16
ETS1	0.016	0.043	-10000	0	-10000	0	0
PXN	0.025	0.17	-10000	0	-0.73	16	16
ITGB1	0.013	0	-10000	0	-10000	0	0
NOS3	0.025	0.18	-10000	0	-0.78	16	16
RAC1	0.013	0	-10000	0	-10000	0	0
TNF	-0.089	0.28	-10000	0	-0.8	53	53
MAPKKK cascade	0.009	0.24	-10000	0	-1.1	16	16
RASA1	0.013	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.002	0.26	-10000	0	-1.2	16	16
NCK1	0.013	0	-10000	0	-10000	0	0
vasculogenesis	0.03	0.14	-10000	0	-0.6	16	16
mol:Phosphatidic acid	0.009	0.24	-10000	0	-1.1	16	16
mol:Angiotensin II	0.001	0.002	-10000	0	-10000	0	0
mol:NADP	0.028	0.16	-10000	0	-0.68	16	16
Rac1/GTP	-0.048	0.16	-10000	0	-0.83	16	16
MMP2	0.001	0.25	-10000	0	-1.2	16	16

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	-0.002	0.032	-10000	0	-0.66	1	1
Necdin/E2F1	-0.066	0.11	-10000	0	-0.82	2	2
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.038	0.11	-10000	0	-0.51	19	19
NGF (dimer)/p75(NTR)/BEX1	-0.3	0.3	-10000	0	-0.6	201	201
NT-4/5 (dimer)/p75(NTR)	-0.075	0.19	-10000	0	-0.69	30	30
IKBKB	0.013	0	-10000	0	-10000	0	0
AKT1	-0.004	0.13	-10000	0	-0.51	20	20
IKBKG	0.013	0	-10000	0	-10000	0	0
BDNF	-0.018	0.15	-10000	0	-0.85	12	12
MGDIs/NGR/p75(NTR)/LINGO1	-0.05	0.13	-10000	0	-0.56	20	20
FURIN	0.013	0	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.062	0.15	-10000	0	-0.59	28	28
LINGO1	-0.001	0.067	-10000	0	-0.31	18	18
Sortilin/TRAF6/NRIF	-0.001	0.021	-10000	0	-10000	0	0
proBDNF (dimer)	-0.018	0.15	-10000	0	-0.85	12	12
NTRK1	0	0.055	-10000	0	-0.31	12	12
RTN4R	0.013	0	-10000	0	-10000	0	0
neuron apoptosis	-0.014	0.14	-10000	0	-0.52	22	22
IRAK1	0.013	0	-10000	0	-10000	0	0
SHC1	-0.022	0.14	-10000	0	-0.59	19	19
ARHGDIA	0.013	0	-10000	0	-10000	0	0
RhoA/GTP	0	0	-10000	0	-10000	0	0
Gamma Secretase	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.042	0.12	-10000	0	-0.55	19	19
MAGEH1	0.013	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.044	0.13	-10000	0	-0.54	21	21
Mammalian IAPs/DIABLO	-0.03	0.12	-10000	0	-0.52	21	21
proNGF (dimer)	0.006	0.075	-10000	0	-0.72	4	4
MAGED1	0.013	0	-10000	0	-10000	0	0
APP	0.013	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.02	0.15	-10000	0	-0.6	22	22
ZNF274	0.013	0	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.039	0.11	-10000	0	-0.51	19	19
NGF	0.006	0.075	-10000	0	-0.72	4	4
cell cycle arrest	0.044	0.17	-10000	0	-0.5	19	19
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.008	0.091	-10000	0	-0.36	20	20
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.065	0.16	-10000	0	-0.61	31	31
NCSTN	0.013	0	-10000	0	-10000	0	0
mol:GTP	-0.047	0.13	-10000	0	-0.59	19	19
PSENEN	0.013	0	-10000	0	-10000	0	0
mol:ceramide	-0.012	0.13	-10000	0	-0.54	19	19
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.02	0.075	-10000	0	-0.45	2	2
p75(NTR)/beta APP	-0.052	0.14	-10000	0	-0.66	17	17
BEX1	-0.38	0.43	-10000	0	-0.85	186	186
mol:GDP	-0.033	0.14	-10000	0	-0.6	19	19
NGF (dimer)	-0.096	0.13	-10000	0	-0.53	26	26
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.044	0.12	-10000	0	-0.55	17	17
PIK3R1	0.013	0	-10000	0	-10000	0	0
RAC1/GTP	-0.041	0.12	-10000	0	-0.52	19	19
MYD88	0.013	0	-10000	0	-10000	0	0
CHUK	0.013	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.047	0.13	-10000	0	-0.6	19	19
RHOB	0.013	0	-10000	0	-10000	0	0
RHOA	0.013	0	-10000	0	-10000	0	0
MAGE-G1/E2F1	-0.063	0.093	-10000	0	-10000	0	0
NT3 (dimer)	-0.051	0.21	-10000	0	-0.63	41	41
TP53	-0.009	0.14	-10000	0	-0.48	29	29
PRDM4	-0.012	0.13	-10000	0	-0.54	19	19
BDNF (dimer)	-0.13	0.17	-10000	0	-0.58	34	34
PIK3CA	0.011	0.043	-10000	0	-0.85	1	1
SORT1	0.013	0	-10000	0	-10000	0	0
activation of caspase activity	-0.037	0.11	-10000	0	-0.5	19	19
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.043	0.12	-10000	0	-0.55	20	20
RHOC	0.013	0	-10000	0	-10000	0	0
XIAP	0.013	0	-10000	0	-10000	0	0
MAPK10	0.021	0.13	-10000	0	-0.46	18	18
DIABLO	0.013	0	-10000	0	-10000	0	0
SMPD2	-0.012	0.13	-10000	0	-0.54	19	19
APH1B	0.013	0	-10000	0	-10000	0	0
APH1A	0.013	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.047	0.13	-10000	0	-0.6	19	19
PSEN1	0.013	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.098	0.21	-10000	0	-0.69	40	40
MAPK8	0.019	0.13	-10000	0	-0.47	18	18
MAPK9	0.021	0.13	-10000	0	-0.45	20	20
APAF1	0.013	0	-10000	0	-10000	0	0
NTF3	-0.051	0.21	-10000	0	-0.63	41	41
NTF4	-0.02	0.15	-10000	0	-0.61	22	22
NDN	0.009	0.06	-10000	0	-0.85	2	2
RAC1/GDP	0	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.034	0.1	-10000	0	-0.47	19	19
p75 CTF/Sortilin/TRAF6/NRIF	-0.002	0.05	-10000	0	-1	1	1
RhoA-B-C/GTP	-0.047	0.13	-10000	0	-0.59	19	19
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.051	0.13	-10000	0	-0.51	29	29
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.056	0.14	-10000	0	-0.54	29	29
PRKACB	0.013	0	-10000	0	-10000	0	0
proBDNF (dimer)/p75 ECD	-0.024	0.12	-10000	0	-0.66	13	13
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.038	0.2	-10000	0	-0.69	30	30
BIRC2	0.013	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.07	0.18	0.25	161	-0.5	19	180
BAD	0.028	0.13	-10000	0	-0.45	18	18
RIPK2	0.013	0	-10000	0	-10000	0	0
NGFR	-0.063	0.2	-10000	0	-0.45	67	67
CYCS	-0.003	0.12	-10000	0	-0.51	19	19
ADAM17	0.011	0.043	-10000	0	-0.85	1	1
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.043	0.12	-10000	0	-0.55	20	20
BCL2L11	0.028	0.13	-10000	0	-0.45	18	18
BDNF (dimer)/p75(NTR)	-0.074	0.18	-10000	0	-0.68	28	28
PI3K	-0.043	0.12	-10000	0	-0.55	20	20
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.042	0.12	-10000	0	-0.55	19	19
NDNL2	0.013	0	-10000	0	-10000	0	0
YWHAE	0.013	0	-10000	0	-10000	0	0
PRKCI	0.013	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.057	0.16	-10000	0	-0.68	19	19
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.042	0.12	-10000	0	-0.55	19	19
TRAF6	0.011	0.043	-10000	0	-0.85	1	1
RAC1	0.013	0	-10000	0	-10000	0	0
PRKCZ	0.013	0	-10000	0	-10000	0	0
PLG	0	0.022	-10000	0	-0.31	2	2
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.021	0.15	-10000	0	-0.51	30	30
SQSTM1	0.013	0	-10000	0	-10000	0	0
NGFRAP1	0.013	0	-10000	0	-10000	0	0
CASP3	0.03	0.12	-10000	0	-0.41	18	18
E2F1	-0.089	0.15	-10000	0	-10000	0	0
CASP9	0.013	0	-10000	0	-10000	0	0
IKK complex	-0.014	0.063	-10000	0	-0.55	3	3
NGF (dimer)/TRKA	-0.011	0.066	-10000	0	-0.66	3	3
MMP7	-0.18	0.23	-10000	0	-0.37	203	203
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.039	0.12	-10000	0	-0.52	20	20
MMP3	-0.041	0.11	-10000	0	-0.31	59	59
APAF-1/Caspase 9	-0.043	0.12	-10000	0	-0.66	6	6

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.012	0.016	-9999	-0.31	1	1
LAT2	-0.016	0.1	-9999	-0.3	13	13
AP1	-0.21	0.29	-9999	-0.6	131	131
mol:PIP3	-0.015	0.16	-9999	-0.44	33	33
IKBKB	0.006	0.093	-9999	-0.28	16	16
AKT1	-0.013	0.13	-9999	-0.48	5	5
IKBKG	0.006	0.093	-9999	-0.28	16	16
MS4A2	-0.063	0.13	-9999	-0.31	91	91
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.011	0.043	-9999	-0.85	1	1
MAP3K1	0.012	0.1	-9999	-0.45	7	7
mol:Ca2+	-0.006	0.12	-9999	-0.33	33	33
LYN	0.01	0.007	-9999	-10000	0	0
CBLB	-0.008	0.088	-9999	-0.33	3	3
SHC1	0.013	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.084	0.19	-9999	-0.53	65	65
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	-0.005	0.075	-9999	-0.31	23	23
PLD2	-0.046	0.15	-9999	-0.46	34	34
PTPN13	0.003	0.087	-9999	-0.46	2	2
PTPN11	0.012	0.006	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	0.021	0.1	-9999	-0.32	4	4
SYK	0.01	0.007	-9999	-10000	0	0
GRB2	0.013	0.001	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.062	0.13	-9999	-0.45	33	33
LAT	-0.014	0.1	-9999	-0.45	7	7
PAK2	0.004	0.11	-9999	-0.51	7	7
NFATC2	-0.13	0.27	-9999	-0.78	59	59
HRAS	-0.005	0.12	-9999	-0.5	10	10
GAB2	0.013	0	-9999	-10000	0	0
PLA2G1B	0.03	0.017	-9999	-10000	0	0
Fc epsilon R1	-0.097	0.17	-9999	-0.49	54	54
Antigen/IgE/Fc epsilon R1	-0.088	0.16	-9999	-0.45	54	54
mol:GDP	-0.014	0.13	-9999	-0.53	12	12
JUN	-0.18	0.36	-9999	-0.85	93	93
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.013	0.001	-9999	-10000	0	0
FOS	-0.21	0.38	-9999	-0.85	106	106
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.042	0.078	-9999	-0.27	28	28
CHUK	0.006	0.093	-9999	-0.27	17	17
KLRG1	-0.02	0.11	-9999	-0.39	13	13
VAV1	-0.02	0.12	-9999	-0.45	10	10
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.008	0.088	-9999	-0.33	3	3
negative regulation of mast cell degranulation	-0.019	0.1	-9999	-0.38	12	12
BTK	-0.045	0.12	-9999	-0.6	10	10
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.049	0.2	-9999	-0.55	38	38
GAB2/PI3K/SHP2	-0.062	0.12	-9999	-0.44	29	29
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.017	0.095	-9999	-0.3	28	28
RAF1	0.017	0.021	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.11	0.21	-9999	-0.61	47	47
FCER1G	-0.009	0.083	-9999	-0.32	27	27
FCER1A	-0.073	0.23	-9999	-0.57	59	59
Antigen/IgE/Fc epsilon R1/Fyn	-0.079	0.15	-9999	-0.5	34	34
MAPK3	0.029	0.018	-9999	-10000	0	0
MAPK1	0.029	0.018	-9999	-10000	0	0
NFKB1	0.013	0	-9999	-10000	0	0
MAPK8	0.015	0.064	-9999	-0.6	3	3
DUSP1	-0.12	0.32	-9999	-0.85	65	65
NF-kappa-B/RelA	-0.018	0.042	-9999	-10000	0	0
actin cytoskeleton reorganization	-0.003	0.082	-9999	-10000	0	0
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.04	0.099	-9999	-0.52	8	8
FER	-0.011	0.093	-9999	-0.39	5	5
RELA	0.013	0	-9999	-10000	0	0
ITK	-0.077	0.18	-9999	-0.54	53	53
SOS1	0.013	0	-9999	-10000	0	0
PLCG1	-0.01	0.13	-9999	-0.52	12	12
cytokine secretion	-0.013	0.031	-9999	-10000	0	0
SPHK1	-0.011	0.09	-9999	-0.33	4	4
PTK2	-0.003	0.085	-9999	-10000	0	0
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.065	0.14	-9999	-0.46	36	36
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.009	0.15	-9999	-0.42	33	33
MAP2K2	0.025	0.018	-9999	-10000	0	0
MAP2K1	0.025	0.018	-9999	-10000	0	0
MAP2K7	0.013	0	-9999	-10000	0	0
KLRG1/SHP2	-0.045	0.089	-9999	-0.4	11	11
MAP2K4	0.021	0.008	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.11	0.22	-9999	-0.66	43	43
mol:Choline	-0.045	0.15	-9999	-0.46	34	34
SHC/Grb2/SOS1	-0.03	0.064	-9999	-10000	0	0
FYN	0.013	0	-9999	-10000	0	0
DOK1	0.013	0	-9999	-10000	0	0
PXN	0.005	0.08	-9999	-10000	0	0
HCLS1	-0.01	0.093	-9999	-0.35	5	5
PRKCB	-0.007	0.12	-9999	-0.34	33	33
FCGR2B	-0.032	0.19	-9999	-0.76	24	24
IGHE	-0.001	0.006	-9999	-10000	0	0
KLRG1/SHIP	-0.019	0.11	-9999	-0.38	12	12
LCP2	0.007	0.046	-9999	-0.32	8	8
PLA2G4A	-0.046	0.17	-9999	-0.52	34	34
RASA1	0.013	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.045	0.15	-9999	-0.46	34	34
IKK complex	0.02	0.075	-9999	-0.23	4	4
WIPF1	0.013	0	-9999	-10000	0	0

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.034	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP1	0	0	-9999	-10000	0	0
mol:DAG	-0.011	0.16	-9999	-0.51	40	40
VEGFR1 homodimer/NRP1/VEGFR 121	-0.003	0.036	-9999	-0.52	2	2
CaM/Ca2+	-0.004	0.16	-9999	-0.47	40	40
HIF1A	0.021	0	-9999	-10000	0	0
GAB1	0.013	0	-9999	-10000	0	0
AKT1	0.011	0.16	-9999	-0.92	1	1
PLCG1	-0.012	0.16	-9999	-0.51	40	40
NOS3	0.018	0.15	-9999	-0.44	40	40
CBL	0.013	0	-9999	-10000	0	0
mol:NO	0.019	0.15	-9999	-0.42	40	40
FLT1	0.033	0	-9999	-10000	0	0
PGF	-0.072	0.26	-9999	-0.84	41	41
VEGFR1 homodimer/NRP2/VEGFR121	-0.013	0.049	-9999	-0.51	2	2
CALM1	0.013	0	-9999	-10000	0	0
PIK3CA	0.011	0.043	-9999	-0.85	1	1
eNOS/Hsp90	0.025	0.14	-9999	-10000	0	0
endothelial cell proliferation	-0.031	0.2	-9999	-0.55	41	41
mol:Ca2+	-0.011	0.16	-9999	-0.5	40	40
MAPK3	-0.022	0.19	-9999	-0.47	60	60
MAPK1	-0.022	0.19	-9999	-0.47	60	60
PIK3R1	0.013	0	-9999	-10000	0	0
PLGF homodimer	-0.072	0.26	-9999	-0.84	41	41
PRKACA	0.013	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.01	0.14	-9999	-0.85	11	11
VEGFA homodimer	0.009	0.06	-9999	-0.85	2	2
VEGFR1 homodimer/VEGFA homodimer	0.031	0.042	-9999	-0.56	2	2
platelet activating factor biosynthetic process	-0.014	0.19	-9999	-0.86	4	4
PI3K	-0.048	0.14	-9999	-0.48	41	41
PRKCA	-0.032	0.2	-9999	-0.5	60	60
PRKCB	-0.019	0.16	-9999	-0.48	42	42
VEGFR1 homodimer/PLGF homodimer	-0.025	0.18	-9999	-0.56	40	40
VEGFA	0.009	0.06	-9999	-0.85	2	2
VEGFB	0.013	0	-9999	-10000	0	0
mol:IP3	-0.011	0.16	-9999	-0.51	40	40
RASA1	0.043	0	-9999	-10000	0	0
NRP2	-0.013	0.089	-9999	-0.31	33	33
VEGFR1 homodimer	0.033	0	-9999	-10000	0	0
VEGFB homodimer	0.013	0	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.013	0.16	-9999	-0.83	2	2
PTPN11	0.013	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.048	0.14	-9999	-0.47	41	41
mol:L-citrulline	0.019	0.15	-9999	-0.42	40	40
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.002	0.033	-9999	-0.48	2	2
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.003	0.036	-9999	-0.51	2	2
CD2AP	0.013	0	-9999	-10000	0	0
PI3K/GAB1	-0.045	0.13	-9999	-0.45	41	41
PDPK1	0.003	0.15	-9999	-0.45	41	41
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.003	0.036	-9999	-0.51	2	2
mol:NADP	0.019	0.15	-9999	-0.42	40	40
HSP90AA1	0.013	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.002	0.033	-9999	-0.47	2	2
VEGFR1 homodimer/NRP2	0.019	0.05	-9999	-10000	0	0

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.021	0.016	-10000	0	-10000	0	0
HSPA8	0.005	0.074	-10000	0	-0.85	3	3
SMAD3/SMAD4/ER alpha	-0.052	0.14	-10000	0	-0.61	19	19
AKT1	0.009	0.01	-10000	0	-10000	0	0
GSC	-0.22	0.57	-10000	0	-1.6	63	63
NKX2-5	0.001	0.031	-10000	0	-10000	0	0
muscle cell differentiation	0.025	0.047	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1	0.003	0.08	-10000	0	-10000	0	0
SMAD4	-0.016	0.059	-10000	0	-10000	0	0
CBFB	0.013	0	-10000	0	-10000	0	0
SAP18	0.011	0.004	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.12	0.078	-10000	0	-0.57	4	4
SMAD3/SMAD4/VDR	0.011	0.045	-10000	0	-10000	0	0
MYC	0.002	0.14	-10000	0	-0.86	10	10
CDKN2B	-0.079	0.14	-10000	0	-10000	0	0
AP1	-0.27	0.53	-10000	0	-1	124	124
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.033	0.042	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.001	0.065	-10000	0	-10000	0	0
SP3	0.016	0.002	-10000	0	-10000	0	0
CREB1	0.013	0	-10000	0	-10000	0	0
FOXH1	-0.009	0.067	-10000	0	-0.3	14	14
SMAD3/SMAD4/GR	-0.017	0.046	-10000	0	-10000	0	0
GATA3	-0.037	0.2	-10000	0	-0.84	23	23
SKI/SIN3/HDAC complex/NCoR1	0.041	0.023	-10000	0	-10000	0	0
MEF2C/TIF2	-0.052	0.14	-10000	0	-0.53	19	19
endothelial cell migration	-0.009	0.11	1.4	1	-10000	0	1
MAX	0.013	0.006	-10000	0	-10000	0	0
RBBP7	0.011	0.004	-10000	0	-10000	0	0
RBBP4	0.011	0.004	-10000	0	-10000	0	0
RUNX2	-0.08	0.16	-10000	0	-0.32	113	113
RUNX3	-0.007	0.12	-10000	0	-0.58	14	14
RUNX1	-0.14	0.16	-10000	0	-10000	0	0
CTBP1	0.013	0	-10000	0	-10000	0	0
NR3C1	0.013	0.006	-10000	0	-10000	0	0
VDR	0.012	0.016	-10000	0	-0.31	1	1
CDKN1A	0.023	0.074	-10000	0	-10000	0	0
KAT2B	0.016	0.005	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	-0.04	0.09	-10000	0	-0.35	1	1
DCP1A	0.013	0	-10000	0	-10000	0	0
SKI	0.011	0.004	-10000	0	-10000	0	0
SERPINE1	0.008	0.11	-10000	0	-1.5	1	1
SMAD3/SMAD4/ATF2	-0.032	0.1	-10000	0	-0.61	10	10
SMAD3/SMAD4/ATF3	-0.16	0.28	-10000	0	-0.65	96	96
SAP30	0.009	0.043	-10000	0	-0.85	1	1
Cbp/p300/PIAS3	0.035	0.046	-10000	0	-10000	0	0
JUN	-0.26	0.52	-10000	0	-0.99	124	124
SMAD3/SMAD4/IRF7	-0.017	0.046	-10000	0	-10000	0	0
TFE3	0.019	0.006	-10000	0	-10000	0	0
COL1A2	-0.002	0.092	-10000	0	-10000	0	0
mesenchymal cell differentiation	0.068	0.098	0.48	4	-10000	0	4
DLX1	-0.04	0.21	-10000	0	-0.85	25	25
TCF3	0.013	0	-10000	0	-10000	0	0
FOS	-0.23	0.41	-10000	0	-0.92	106	106
SMAD3/SMAD4/Max	-0.017	0.046	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.009	0.021	-10000	0	-10000	0	0
ZBTB17	0.021	0.012	-10000	0	-10000	0	0
LAMC1	0.025	0.054	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	-0.017	0.045	-10000	0	-10000	0	0
IRF7	0.014	0.005	-10000	0	-10000	0	0
ESR1	-0.049	0.2	-10000	0	-0.85	19	19
HNF4A	-0.004	0.047	-10000	0	-0.31	9	9
MEF2C	0.005	0.087	-10000	0	-10000	0	0
SMAD2-3/SMAD4	-0.033	0.056	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.025	0.031	-10000	0	-10000	0	0
IGHV3OR16-13	-0.017	0.024	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.013	0	-10000	0	-10000	0	0
CREBBP	0.018	0.011	-10000	0	-10000	0	0
SKIL	0.013	0	-10000	0	-10000	0	0
HDAC1	0.011	0.004	-10000	0	-10000	0	0
HDAC2	0.011	0.004	-10000	0	-10000	0	0
SNIP1	0.011	0.005	-10000	0	-10000	0	0
GCN5L2	0.006	0.012	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	-0.012	0.045	-10000	0	-10000	0	0
MSG1/HSC70	-0.18	0.1	-10000	0	-0.7	7	7
SMAD2	-0.004	0.04	-10000	0	-10000	0	0
SMAD3	-0.005	0.048	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.015	0.059	-10000	0	-0.37	4	4
SMAD2/SMAD2/SMAD4	0.013	0.026	-10000	0	-10000	0	0
NCOR1	0.011	0.004	-10000	0	-10000	0	0
NCOA2	-0.05	0.22	-10000	0	-0.85	30	30
NCOA1	0.013	0	-10000	0	-10000	0	0
MYOD/E2A	-0.002	0.02	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.011	0.076	-10000	0	-10000	0	0
IFNB1	0.015	0.059	-10000	0	-10000	0	0
SMAD3/SMAD4/MEF2C	-0.006	0.088	-10000	0	-10000	0	0
CITED1	-0.26	0.14	-10000	0	-0.32	335	335
SMAD2-3/SMAD4/ARC105	-0.024	0.045	-10000	0	-10000	0	0
RBL1	0	0.1	-10000	0	-0.85	6	6
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.007	0.081	-10000	0	-10000	0	0
RUNX1-3/PEBPB2	-0.085	0.11	-10000	0	-0.61	7	7
SMAD7	-0.11	0.28	-10000	0	-0.6	83	83
MYC/MIZ-1	0.014	0.11	-10000	0	-0.66	10	10
SMAD3/SMAD4	0.066	0.1	0.31	38	-0.35	1	39
IL10	-0.031	0.2	-10000	0	-0.64	34	34
PIASy/HDAC complex	0.007	0.009	-10000	0	-10000	0	0
PIAS3	0.015	0.006	-10000	0	-10000	0	0
CDK2	0.018	0.011	-10000	0	-10000	0	0
IL5	-0.02	0.15	-10000	0	-0.53	23	23
CDK4	0.019	0.013	-10000	0	-10000	0	0
PIAS4	0.007	0.009	-10000	0	-10000	0	0
ATF3	-0.19	0.37	-10000	0	-0.82	102	102
SMAD3/SMAD4/SP1	-0.018	0.053	-10000	0	-10000	0	0
FOXG1	-0.007	0.09	-10000	0	-0.43	14	14
FOXO3	0.017	0.015	-10000	0	-10000	0	0
FOXO1	0.017	0.015	-10000	0	-10000	0	0
FOXO4	0.017	0.015	-10000	0	-10000	0	0
heart looping	0.005	0.087	-10000	0	-10000	0	0
CEBPB	0.009	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.055	0.15	-10000	0	-0.63	25	25
MYOD1	-0.002	0.031	-10000	0	-0.31	4	4
SMAD3/SMAD4/HNF4	-0.024	0.054	-10000	0	-0.4	1	1
SMAD3/SMAD4/GATA3	-0.055	0.15	-10000	0	-0.56	28	28
SnoN/SIN3/HDAC complex/NCoR1	0.013	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.079	0.11	-10000	0	-0.57	9	9
SMAD3/SMAD4/SP1-3	-0.006	0.047	-10000	0	-10000	0	0
MED15	0.013	0	-10000	0	-10000	0	0
SP1	0.014	0.022	-10000	0	-10000	0	0
SIN3B	0.011	0.004	-10000	0	-10000	0	0
SIN3A	0.011	0.004	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.031	0.082	-10000	0	-10000	0	0
ITGB5	0.035	0.06	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.042	0.022	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.27	0.3	-10000	0	-0.62	170	170
AR	-0.35	0.43	-10000	0	-0.85	170	170
negative regulation of cell growth	-0.038	0.12	-10000	0	-0.4	3	3
SMAD3/SMAD4/MYOD	-0.023	0.051	-10000	0	-10000	0	0
E2F5	0.013	0	-10000	0	-10000	0	0
E2F4	0.013	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.02	0.058	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4	-0.001	0.067	-10000	0	-10000	0	0
TFDP1	0.013	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	-0.28	0.54	-10000	0	-1	124	124
SMAD3/SMAD4/RUNX2	-0.068	0.099	-10000	0	-0.48	4	4
TGIF2	0.013	0	-10000	0	-10000	0	0
TGIF1	0.013	0	-10000	0	-10000	0	0
ATF2	-0.008	0.13	-10000	0	-0.85	10	10

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	-0.017	0.089	-9999	-0.5	13	13
RGS9BP	-0.042	0.21	-9999	-0.85	26	26
mol:GTP	0	0	-9999	-10000	0	0
GRK1	-0.072	0.26	-9999	-0.84	41	41
mol:Na +	-0.022	0.057	-9999	-10000	0	0
mol:ADP	-0.049	0.2	-9999	-0.66	40	40
GNAT2	0.009	0.023	-9999	-0.31	2	2
RGS9-1/Gbeta5/R9AP	-0.095	0.22	-9999	-0.58	66	66
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.001	0.012	-9999	-10000	0	0
GRK7	0.007	0.007	-9999	-10000	0	0
CNGB3	0.003	0.005	-9999	-10000	0	0
Cone Metarhodopsin II/X-Arrestin	0	0	-9999	-10000	0	0
mol:Ca2+	-0.014	0.065	-9999	-0.31	2	2
Cone PDE6	-0.083	0.19	-9999	-0.51	66	66
Cone Metarhodopsin II	-0.053	0.16	-9999	-0.54	40	40
Na + (4 Units)	-0.025	0.06	-9999	-10000	0	0
GNAT2/GDP	-0.083	0.19	-9999	-0.51	66	66
GNB5	0.013	0	-9999	-10000	0	0
mol:GMP (4 units)	0.012	0.014	-9999	-10000	0	0
Cone Transducin	-0.018	0.093	-9999	-0.53	13	13
SLC24A2	-0.01	0.065	-9999	-0.31	18	18
GNB3/GNGT2	-0.022	0.12	-9999	-0.66	13	13
GNB3	-0.014	0.15	-9999	-0.85	13	13
GNAT2/GTP	-0.001	0.015	-9999	-10000	0	0
CNGA3	-0.028	0.11	-9999	-0.31	51	51
ARR3	0.004	0.006	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.022	0.057	-9999	-10000	0	0
mol:Pi	-0.095	0.22	-9999	-0.58	66	66
Cone CNG Channel	-0.016	0.043	-9999	-10000	0	0
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.01	0.065	-9999	-0.31	18	18
RGS9	-0.077	0.26	-9999	-0.83	44	44
PDE6C	0.004	0.006	-9999	-10000	0	0
GNGT2	0.012	0.023	-9999	-0.31	2	2
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.004	0.006	-9999	-10000	0	0

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.062	0.15	-9999	-0.45	54	54
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
CRKL	0.013	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	-0.051	0.12	-9999	-10000	0	0
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.009	0.023	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.024	0.061	-9999	-0.27	1	1
CaM/Ca2+	-0.057	0.14	-9999	-0.42	54	54
RAP1A	0.013	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.022	0.16	-9999	-0.42	54	54
AKT1	-0.004	0.15	-9999	-0.41	3	3
MAP2K1	-0.007	0.15	-9999	-0.39	54	54
MAP3K11	-0.018	0.16	-9999	-0.42	54	54
IFNGR1	0.009	0.014	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.026	0.07	-9999	-0.66	1	1
Rap1/GTP	-0.042	0.1	-9999	-10000	0	0
CRKL/C3G	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.065	0.16	-9999	-0.47	54	54
CEBPB	0.016	0.17	-9999	-0.78	2	2
STAT3	0.013	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.058	0.14	-9999	-10000	0	0
STAT1	-0.021	0.16	-9999	-0.42	54	54
CALM1	0.013	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.11	0.29	-9999	-0.75	65	65
PIK3CA	0.011	0.043	-9999	-0.85	1	1
STAT1 (dimer)/PIAS1	-0.048	0.14	-9999	-0.39	54	54
CEBPB/PTGES2/Cbp/p300	-0.036	0.081	-9999	-0.43	2	2
mol:Ca2+	-0.061	0.15	-9999	-0.44	54	54
MAPK3	0.008	0.14	-9999	-0.49	2	2
STAT1 (dimer)	-0.031	0.081	-9999	-0.37	1	1
MAPK1	0.008	0.14	-9999	-0.49	2	2
JAK2	0.009	0.014	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
JAK1	0.009	0.014	-9999	-10000	0	0
CAMK2D	0.013	0	-9999	-10000	0	0
DAPK1	0.013	0.18	-9999	-0.66	20	20
SMAD7	0.041	0.056	-9999	-10000	0	0
CBL/CRKL/C3G	-0.051	0.13	-9999	-10000	0	0
PI3K	-0.056	0.14	-9999	-0.4	55	55
IFNG	-0.11	0.29	-9999	-0.76	65	65
apoptosis	0.011	0.13	-9999	-0.44	20	20
CAMK2G	0.013	0	-9999	-10000	0	0
STAT3 (dimer)	0.013	0	-9999	-10000	0	0
CAMK2A	-0.003	0.065	-9999	-0.31	17	17
CAMK2B	0.003	0.095	-9999	-0.85	5	5
FRAP1	0	0.14	-9999	-0.38	3	3
PRKCD	-0.002	0.15	-9999	-0.41	3	3
RAP1B	0.013	0	-9999	-10000	0	0
negative regulation of cell growth	-0.024	0.061	-9999	-0.27	1	1
PTPN2	0.013	0	-9999	-10000	0	0
EP300	0.014	0	-9999	-10000	0	0
IRF1	0.029	0.12	-9999	-0.4	1	1
STAT1 (dimer)/PIASy	-0.056	0.14	-9999	-0.4	54	54
SOCS1	0.005	0.025	-9999	-10000	0	0
mol:GDP	-0.049	0.12	-9999	-10000	0	0
CASP1	0.039	0.064	-9999	-0.36	2	2
PTGES2	0.013	0	-9999	-10000	0	0
IRF9	0.041	0.058	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.055	0.13	-9999	-0.39	55	55
RAP1/GDP	-0.042	0.11	-9999	-10000	0	0
CBL	-0.019	0.16	-9999	-0.42	54	54
MAP3K1	-0.018	0.16	-9999	-0.42	54	54
PIAS1	0.013	0	-9999	-10000	0	0
PIAS4	0.013	0	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.024	0.061	-9999	-0.27	1	1
PTPN11	-0.028	0.16	-9999	-0.45	54	54
CREBBP	0.014	0	-9999	-10000	0	0
RAPGEF1	0.013	0	-9999	-10000	0	0

×

Syndecan-3-mediated signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.013	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.044	0.13	-9999	-0.44	40	40
Syndecan-3/Neurocan	-0.043	0.14	-9999	-0.49	35	35
POMC	-0.17	0.35	-9999	-0.83	88	88
EGFR	0.003	0.095	-9999	-0.85	5	5
Syndecan-3/EGFR	-0.006	0.054	-9999	-0.49	5	5
AGRP	-0.003	0.059	-9999	-0.31	14	14
NCSTN	0.013	0	-9999	-10000	0	0
PSENEN	0.013	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.013	0	-9999	-10000	0	0
APH1A	0.013	0	-9999	-10000	0	0
NCAN	-0.064	0.24	-9999	-0.81	38	38
long-term memory	0	0.004	-9999	-10000	0	0
Syndecan-3/IL8	-0.04	0.082	-9999	-0.49	8	8
PSEN1	0.013	0	-9999	-10000	0	0
Src/Cortactin	0	0.01	-9999	-10000	0	0
FYN	0.013	0	-9999	-10000	0	0
limb bud formation	0	0.006	-9999	-10000	0	0
MC4R	0.001	0.039	-9999	-0.31	6	6
SRC	0.012	0.016	-9999	-0.31	1	1
PTN	-0.072	0.26	-9999	-0.84	41	41
FGFR/FGF/Syndecan-3	0	0.006	-9999	-10000	0	0
neuron projection morphogenesis	-0.079	0.17	-9999	-0.43	74	74
Syndecan-3/AgRP	-0.005	0.023	-9999	-10000	0	0
Syndecan-3/AgRP/MC4R	-0.006	0.025	-9999	-10000	0	0
Fyn/Cortactin	0	0	-9999	-10000	0	0
SDC3	0	0.006	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.039	0.081	-9999	-0.48	8	8
IL8	-0.084	0.18	-9999	-0.35	108	108
Syndecan-3/Fyn/Cortactin	0	0.004	-9999	-10000	0	0
Syndecan-3/CASK	0	0.006	-9999	-10000	0	0
alpha-MSH/MC4R	-0.14	0.27	-9999	-0.66	85	85
Gamma Secretase	0	0	-9999	-10000	0	0

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.25	0.4	-10000	0	-0.85	126	126
HRAS	0.012	0.023	-10000	0	-0.31	2	2
EGFR	0.003	0.095	-10000	0	-0.85	5	5
AKT	0.018	0.025	0.21	1	-10000	0	1
FOXO3	0.013	0	-10000	0	-10000	0	0
AKT1	0.013	0	-10000	0	-10000	0	0
FOXO1	0.013	0	-10000	0	-10000	0	0
AKT3	0.013	0	-10000	0	-10000	0	0
FOXO4	0.013	0	-10000	0	-10000	0	0
MET	-0.12	0.16	-10000	0	-0.31	164	164
PIK3CA	0.011	0.043	-10000	0	-0.85	1	1
PIK3CB	0.013	0	-10000	0	-10000	0	0
NRAS	0.013	0	-10000	0	-10000	0	0
PIK3CG	-0.008	0.13	-10000	0	-0.75	11	11
PIK3R3	0.011	0.043	-10000	0	-0.85	1	1
PIK3R2	0.013	0	-10000	0	-10000	0	0
NF1	0.013	0	-10000	0	-10000	0	0
RAS	-0.063	0.1	-10000	0	-0.28	40	40
ERBB2	0.013	0	-10000	0	-10000	0	0
proliferation/survival/translation	-0.025	0.022	0.17	1	-0.17	1	2
PI3K	-0.041	0.098	0.23	1	-0.23	43	44
PIK3R1	0.013	0	-10000	0	-10000	0	0
KRAS	0.013	0	-10000	0	-10000	0	0
FOXO	0.024	0.026	0.2	1	-10000	0	1
AKT2	0.013	0	-10000	0	-10000	0	0
PTEN	0.011	0.043	-10000	0	-0.85	1	1

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.013	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.067	0.085	-10000	0	-0.35	20	20
NT3 (dimer)/TRKC	-0.095	0.2	-10000	0	-0.7	35	35
NT3 (dimer)/TRKB	-0.087	0.19	-10000	0	-0.6	43	43
SHC/Grb2/SOS1/GAB1/PI3K	0.039	0.019	-10000	0	-0.34	1	1
RAPGEF1	0.013	0	-10000	0	-10000	0	0
BDNF	-0.018	0.15	-10000	0	-0.85	12	12
PIK3CA	0.011	0.043	-10000	0	-0.85	1	1
DYNLT1	0.013	0	-10000	0	-10000	0	0
NTRK1	0	0.055	-10000	0	-0.31	12	12
NTRK2	0.007	0.074	-10000	0	-0.85	3	3
NTRK3	-0.061	0.18	-10000	0	-0.4	73	73
NT-4/5 (dimer)/TRKB	-0.067	0.17	-10000	0	-0.6	33	33
neuron apoptosis	0.042	0.096	0.45	11	-10000	0	11
SHC 2-3/Grb2	-0.045	0.1	-10000	0	-0.49	11	11
SHC1	0.013	0	-10000	0	-10000	0	0
SHC2	-0.031	0.098	-10000	0	-0.68	5	5
SHC3	-0.049	0.1	-10000	0	-0.57	10	10
STAT3 (dimer)	0.017	0.026	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	-0.088	0.18	-10000	0	-0.6	41	41
RIN/GDP	-0.01	0.064	-10000	0	-0.29	2	2
GIPC1	0.013	0	-10000	0	-10000	0	0
KRAS	0.013	0	-10000	0	-10000	0	0
DNAJA3	-0.032	0.098	-10000	0	-0.44	20	20
RIN/GTP	0	0	-10000	0	-10000	0	0
CCND1	0.025	0.047	-10000	0	-10000	0	0
MAGED1	0.013	0	-10000	0	-10000	0	0
PTPN11	0.013	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.02	0.15	-10000	0	-0.6	22	22
SHC/GRB2/SOS1	0	0	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.018	0.085	-10000	0	-0.57	8	8
TRKA/NEDD4-2	-0.006	0.034	-10000	0	-10000	0	0
ELMO1	-0.32	0.42	-10000	0	-0.85	159	159
RhoG/GTP/ELMO1/DOCK1	-0.23	0.29	-10000	0	-0.58	159	159
NGF	0.006	0.075	-10000	0	-0.72	4	4
HRAS	0.012	0.023	-10000	0	-0.31	2	2
DOCK1	0.009	0.06	-10000	0	-0.85	2	2
GAB2	0.013	0	-10000	0	-10000	0	0
RIT2	0.002	0.005	-10000	0	-10000	0	0
RIT1	0.013	0	-10000	0	-10000	0	0
FRS2	0.013	0	-10000	0	-10000	0	0
DNM1	-0.026	0.18	-10000	0	-0.82	19	19
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.013	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.21	0.24	-10000	0	-0.49	174	174
mol:GDP	-0.017	0.093	-10000	0	-0.41	4	4
NGF (dimer)	0.006	0.075	-10000	0	-0.72	4	4
RhoG/GDP	-0.26	0.32	-10000	0	-0.67	159	159
RIT1/GDP	-0.005	0.065	-10000	0	-0.28	2	2
TIAM1	-0.17	0.16	-10000	0	-0.32	230	230
PIK3R1	0.013	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.023	0.12	-10000	0	-0.65	13	13
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0	0	-10000	0	-10000	0	0
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.051	0.21	-10000	0	-0.63	41	41
RAP1/GDP	-0.019	0.044	-10000	0	-0.26	1	1
KIDINS220/CRKL	0.013	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.018	0.15	-10000	0	-0.85	12	12
ubiquitin-dependent protein catabolic process	-0.009	0.055	-10000	0	-0.57	3	3
Schwann cell development	-0.043	0.033	-10000	0	-10000	0	0
EHD4	0.013	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.043	0	-10000	0	-10000	0	0
RAP1B	0.013	0	-10000	0	-10000	0	0
RAP1A	0.013	0	-10000	0	-10000	0	0
CDC42/GTP	-0.072	0.16	-10000	0	-0.71	12	12
ABL1	0.013	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
Rap1/GTP	-0.007	0.037	-10000	0	-10000	0	0
STAT3	0.017	0.026	-10000	0	-10000	0	0
axon guidance	-0.069	0.16	-10000	0	-0.48	45	45
MAPK3	0.016	0.083	-10000	0	-0.52	8	8
MAPK1	0.016	0.083	-10000	0	-0.52	8	8
CDC42/GDP	-0.005	0.065	-10000	0	-0.28	2	2
NTF3	-0.051	0.21	-10000	0	-0.63	41	41
NTF4	-0.02	0.15	-10000	0	-0.61	22	22
NGF (dimer)/TRKA/FAIM	-0.009	0.056	-10000	0	-0.57	3	3
PI3K	-0.002	0.032	-10000	0	-0.66	1	1
FRS3	0.013	0	-10000	0	-10000	0	0
FAIM	0.013	0	-10000	0	-10000	0	0
GAB1	0.013	0	-10000	0	-10000	0	0
RASGRF1	-0.13	0.12	-10000	0	-0.51	24	24
SOS1	0.013	0	-10000	0	-10000	0	0
MCF2L	-0.058	0.19	-10000	0	-0.61	35	35
RGS19	0.013	0	-10000	0	-10000	0	0
CDC42	0.013	0	-10000	0	-10000	0	0
RAS family/GTP	0.002	0.045	-10000	0	-10000	0	0
Rac1/GDP	-0.005	0.065	-10000	0	-0.28	2	2
NGF (dimer)/TRKA/GRIT	-0.01	0.057	-10000	0	-0.58	3	3
neuron projection morphogenesis	0	0.1	-10000	0	-0.53	3	3
NGF (dimer)/TRKA/NEDD4-2	-0.009	0.056	-10000	0	-0.57	3	3
MAP2K1	0.042	0	-10000	0	-10000	0	0
NGFR	-0.063	0.2	-10000	0	-0.45	67	67
NGF (dimer)/TRKA/GIPC/GAIP	0.015	0.088	-10000	0	-0.36	20	20
RAS family/GTP/PI3K	0.032	0.024	-10000	0	-0.44	1	1
FRS2 family/SHP2/GRB2/SOS1	0	0	-10000	0	-10000	0	0
NRAS	0.013	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
PRKCI	0.013	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
PRKCZ	0.013	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.009	0.061	-10000	0	-0.62	3	3
RASA1	0.013	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.006	0.034	-10000	0	-10000	0	0
SQSTM1	0.013	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.021	0.11	-10000	0	-0.6	13	13
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.007	0.046	-10000	0	-0.49	3	3
MATK	-0.001	0.1	-10000	0	-0.58	10	10
NEDD4L	0.013	0	-10000	0	-10000	0	0
RAS family/GDP	-0.016	0.043	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.036	0.1	-10000	0	-0.47	20	20
Rac1/GTP	-0.19	0.15	-10000	0	-0.36	163	163
FRS2 family/SHP2/CRK family	0	0	-10000	0	-10000	0	0

×

Aurora B 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.002	0.082	-9999	-10000	0	0
STMN1	-0.021	0.094	-9999	-0.39	1	1
Aurora B/RasGAP/Survivin	-0.026	0.11	-9999	-0.33	33	33
Chromosomal passenger complex/Cul3 protein complex	0.008	0.068	-9999	-0.29	10	10
BIRC5	-0.018	0.1	-9999	-0.34	36	36
DES	-0.38	0.3	-9999	-0.62	249	249
Aurora C/Aurora B/INCENP	-0.013	0.077	-9999	-10000	0	0
Aurora B/TACC1	-0.02	0.075	-9999	-10000	0	0
Aurora B/PP2A	-0.027	0.091	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CBX5	0.005	0.025	-9999	-10000	0	0
mitotic metaphase/anaphase transition	0.001	0.003	-9999	-10000	0	0
NDC80	-0.053	0.15	-9999	-0.39	56	56
Cul3 protein complex	-0.016	0.086	-9999	-0.57	9	9
KIF2C	-0.002	0.043	-9999	-10000	0	0
PEBP1	0.01	0.005	-9999	-10000	0	0
KIF20A	-0.058	0.14	-9999	-0.31	90	90
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.027	0.091	-9999	-10000	0	0
SEPT1	0.008	0.039	-9999	-0.31	6	6
SMC2	0.013	0	-9999	-10000	0	0
SMC4	0.013	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	0.006	0.044	-9999	-10000	0	0
PSMA3	0.013	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.001	-9999	-10000	0	0
H3F3B	-0.007	0.055	-9999	-10000	0	0
AURKB	-0.05	0.14	-9999	-0.31	91	91
AURKC	0.004	0.055	-9999	-0.31	12	12
CDCA8	0.009	0.029	-9999	-0.33	3	3
cytokinesis	-0.069	0.08	-9999	-0.38	9	9
Aurora B/Septin1	-0.029	0.1	-9999	-0.42	6	6
AURKA	0.012	0.002	-9999	-10000	0	0
INCENP	0.012	0.006	-9999	-10000	0	0
KLHL13	-0.014	0.14	-9999	-0.57	19	19
BUB1	-0.11	0.16	-9999	-0.31	154	154
hSgo1/Aurora B/Survivin	-0.03	0.12	-9999	-0.46	17	17
EVI5	0.014	0.001	-9999	-10000	0	0
RhoA/GTP	-0.033	0.074	-9999	-0.36	3	3
SGOL1	-0.003	0.079	-9999	-0.34	19	19
CENPA	-0.008	0.069	-9999	-0.21	10	10
NCAPG	-0.028	0.11	-9999	-0.31	51	51
Aurora B/HC8 Proteasome	-0.027	0.091	-9999	-10000	0	0
NCAPD2	0.013	0	-9999	-10000	0	0
Aurora B/PP1-gamma	-0.027	0.091	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
NCAPH	-0.036	0.12	-9999	-0.31	61	61
NPM1	-0.012	0.048	-9999	-10000	0	0
RASA1	0.013	0	-9999	-10000	0	0
KLHL9	0.013	0	-9999	-10000	0	0
mitotic prometaphase	-0.001	0.003	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.027	0.09	-9999	-10000	0	0
PPP1CC	0.013	0	-9999	-10000	0	0
Centraspindlin	-0.037	0.082	-9999	-0.35	16	16
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.012	0.048	-9999	-10000	0	0
MYLK	-0.007	0.055	-9999	-10000	0	0
KIF23	-0.006	0.076	-9999	-0.32	23	23
VIM	-0.021	0.093	-9999	-10000	0	0
RACGAP1	0.012	0.003	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
NCL	-0.012	0.048	-9999	-10000	0	0
Chromosomal passenger complex	-0.016	0.084	-9999	-0.25	21	21
Chromosomal passenger complex/EVI5	0.012	0.12	-9999	-0.43	4	4
TACC1	0.013	0	-9999	-10000	0	0
PPP2R5D	0.013	0	-9999	-10000	0	0
CUL3	0.013	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.015	0.093	-10000	0	-0.33	4	4
epithelial cell differentiation	-0.044	0.097	-10000	0	-0.5	8	8
ITCH	0.024	0.021	-10000	0	-10000	0	0
WWP1	-0.002	0.08	-10000	0	-10000	0	0
FYN	0.013	0	-10000	0	-10000	0	0
EGFR	0.003	0.095	-10000	0	-0.85	5	5
PRL	0.001	0.016	-10000	0	-0.31	1	1
neuron projection morphogenesis	-0.001	0.15	-10000	0	-0.54	8	8
PTPRZ1	-0.02	0.15	-10000	0	-0.6	21	21
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.062	0.14	-10000	0	-0.61	8	8
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.049	0.18	-10000	0	-0.55	40	40
ADAM17	0.022	0.048	-10000	0	-0.85	1	1
ErbB4/ErbB4	-0.012	0.1	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.049	0.18	-10000	0	-0.59	31	31
NCOR1	0.013	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.072	0.16	-10000	0	-0.52	40	40
GRIN2B	-0.034	0.16	-10000	0	-0.49	40	40
ErbB4/ErbB2/betacellulin	-0.035	0.1	-10000	0	-0.63	9	9
STAT1	0.006	0.048	-10000	0	-0.31	9	9
HBEGF	-0.004	0.072	-10000	0	-0.31	21	21
PRLR	-0.042	0.19	-10000	0	-0.58	38	38
E4ICDs/ETO2	-0.006	0.086	-10000	0	-0.33	1	1
axon guidance	0	0.082	-10000	0	-0.33	2	2
NEDD4	0.022	0.048	-10000	0	-0.85	1	1
Prolactin receptor/Prolactin receptor/Prolactin	-0.041	0.14	-10000	0	-0.67	19	19
CBFA2T3	0.012	0.016	-10000	0	-0.31	1	1
ErbB4/ErbB2/HBEGF	-0.029	0.058	-10000	0	-0.67	1	1
MAPK3	-0.01	0.15	-10000	0	-0.57	8	8
STAT1 (dimer)	-0.009	0.09	-10000	0	-0.33	3	3
MAPK1	-0.01	0.15	-10000	0	-0.57	8	8
JAK2	0.013	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.072	0.16	-10000	0	-0.52	40	40
NRG1	-0.039	0.21	-10000	0	-0.68	40	40
NRG3	-0.053	0.23	-10000	0	-0.85	31	31
NRG2	-0.095	0.28	-10000	0	-0.82	53	53
NRG4	0.007	0.039	-10000	0	-0.31	6	6
heart development	0	0.082	-10000	0	-0.33	2	2
neural crest cell migration	-0.071	0.15	-10000	0	-0.51	40	40
ERBB2	0.029	0.035	-10000	0	-0.64	1	1
WWOX/E4ICDs	-0.006	0.085	-10000	0	-10000	0	0
SHC1	0.013	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.04	0.089	-10000	0	-0.59	5	5
apoptosis	0.059	0.14	0.48	31	-10000	0	31
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.077	0.2	-10000	0	-0.57	51	51
ErbB4/ErbB2/epiregulin	-0.078	0.085	-10000	0	-0.67	1	1
ErbB4/ErbB4/betacellulin/betacellulin	-0.018	0.13	-10000	0	-0.67	9	9
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.059	0.12	-10000	0	-0.5	19	19
MDM2	-0.001	0.088	-10000	0	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.066	0.16	-10000	0	-0.53	40	40
STAT5A	0.008	0.077	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.078	0.17	-10000	0	-0.53	44	44
DLG4	0.013	0	-10000	0	-10000	0	0
GRB2/SHC	0	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.033	0.063	-10000	0	-10000	0	0
STAT5A (dimer)	-0.047	0.1	-10000	0	-0.54	8	8
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.007	0.075	-10000	0	-10000	0	0
LRIG1	0.007	0.074	-10000	0	-0.85	3	3
EREG	-0.14	0.16	-10000	0	-0.31	189	189
BTC	-0.006	0.13	-10000	0	-0.85	9	9
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0	0.083	-10000	0	-0.33	2	2
ERBB4	-0.012	0.1	-10000	0	-10000	0	0
STAT5B	0.013	0	-10000	0	-10000	0	0
YAP1	-0.011	0.021	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.026	0.054	-10000	0	-0.53	1	1
glial cell differentiation	0.033	0.063	-10000	0	-10000	0	0
WWOX	0.013	0	-10000	0	-10000	0	0
cell proliferation	-0.024	0.17	-10000	0	-0.47	44	44

×

Aurora C signaling

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
INCENP	0.013	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.035	0.065	-9999	-10000	0	0
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.01	0.018	-9999	-10000	0	0
AURKB	-0.06	0.14	-9999	-0.31	91	91
AURKC	0.004	0.055	-9999	-0.31	12	12

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.013	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.022	0.12	-9999	-0.7	13	13
PTK2	-0.036	0.15	-9999	-0.64	20	20
positive regulation of JNK cascade	-0.018	0.076	-9999	-0.35	20	20
CDC42/GDP	0.035	0.12	-9999	-0.48	20	20
Rac1/GDP	0.037	0.12	-9999	-0.48	20	20
RAP1B	0.013	0	-9999	-10000	0	0
RAP1A	0.013	0	-9999	-10000	0	0
CTNNB1	0.013	0	-9999	-10000	0	0
CDC42/GTP	-0.022	0.095	-9999	-0.44	20	20
nectin-3/I-afadin	-0.032	0.14	-9999	-0.66	20	20
RAPGEF1	0.028	0.13	-9999	-0.55	20	20
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.018	0.15	-9999	-0.65	20	20
PDGFB-D/PDGFRB	0.013	0	-9999	-10000	0	0
TLN1	0.021	0.076	-9999	-0.97	1	1
Rap1/GTP	-0.019	0.082	-9999	-0.38	20	20
IQGAP1	0.013	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.032	0.14	-9999	-0.66	20	20
PVR	0.013	0	-9999	-10000	0	0
Necl-5(dimer)	0.013	0	-9999	-10000	0	0
mol:GDP	0.029	0.15	-9999	-0.61	20	20
MLLT4	0.013	0	-9999	-10000	0	0
PIK3CA	0.011	0.043	-9999	-0.85	1	1
PI3K	-0.025	0.11	-9999	-0.51	20	20
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.005	0.031	-9999	-10000	0	0
positive regulation of lamellipodium assembly	-0.019	0.08	-9999	-0.37	20	20
PVRL1	0.005	0.05	-9999	-0.31	10	10
PVRL3	-0.029	0.19	-9999	-0.85	20	20
PVRL2	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
CDH1	0.013	0	-9999	-10000	0	0
CLDN1	-0.26	0.16	-9999	-0.33	331	331
JAM-A/CLDN1	-0.14	0.14	-9999	-0.58	30	30
SRC	-0.038	0.16	-9999	-0.74	20	20
ITGB3	-0.014	0.15	-9999	-0.85	13	13
nectin-1(dimer)/I-afadin/I-afadin	-0.005	0.031	-9999	-10000	0	0
FARP2	0.023	0.14	-9999	-0.6	20	20
RAC1	0.013	0	-9999	-10000	0	0
CTNNA1	0.013	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.028	0.12	-9999	-0.57	20	20
nectin-1/I-afadin	-0.005	0.031	-9999	-10000	0	0
nectin-2/I-afadin	0	0	-9999	-10000	0	0
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	-0.032	0.12	-9999	-0.57	20	20
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0.013	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.018	0.076	-9999	-0.35	20	20
alphaV/beta3 Integrin/Talin	0.018	0.13	-9999	-0.63	13	13
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
PIP5K1C	0.013	0.08	-9999	-1	1	1
VAV2	0.022	0.14	-9999	-0.61	20	20
RAP1/GDP	-0.022	0.096	-9999	-0.44	20	20
ITGAV	0.011	0.043	-9999	-0.85	1	1
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.028	0.12	-9999	-0.57	20	20
nectin-3(dimer)/I-afadin/I-afadin	-0.032	0.14	-9999	-0.66	20	20
Rac1/GTP	-0.023	0.099	-9999	-0.46	20	20
PTPRM	-0.017	0.083	-9999	-0.34	20	20
E-cadherin/beta catenin/alpha catenin	-0.002	0.015	-9999	-10000	0	0
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.013	0	-9999	-10000	0	0

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	0.049	0.35	-9999	-0.94	11	11
PLK1	0.042	0.073	-9999	-10000	0	0
BIRC5	0.023	0.13	-9999	-1.6	1	1
HSPA1B	0.049	0.35	-9999	-0.94	11	11
MAP2K1	0.032	0.037	-9999	-10000	0	0
BRCA2	0.042	0.36	-9999	-1	14	14
FOXM1	0.037	0.39	-9999	-1.1	13	13
XRCC1	0.049	0.35	-9999	-0.94	11	11
FOXM1B/p19	-0.094	0.3	-9999	-0.92	19	19
Cyclin D1/CDK4	0.034	0.33	-9999	-0.88	10	10
CDC2	0.042	0.36	-9999	-0.95	13	13
TGFA	0.016	0.34	-9999	-0.86	13	13
SKP2	0.046	0.35	-9999	-0.95	12	12
CCNE1	0.016	0.01	-9999	-10000	0	0
CKS1B	0.049	0.35	-9999	-0.94	11	11
RB1	-0.052	0.095	-9999	-10000	0	0
FOXM1C/SP1	0.034	0.36	-9999	-1	12	12
AURKB	-0.005	0.13	-9999	-10000	0	0
CENPF	0.042	0.36	-9999	-0.97	12	12
CDK4	0.018	0.015	-9999	-10000	0	0
MYC	0.041	0.35	-9999	-0.9	16	16
CHEK2	0.032	0.037	-9999	-10000	0	0
ONECUT1	0.031	0.34	-9999	-0.93	11	11
CDKN2A	-0.12	0.16	-9999	-0.31	165	165
LAMA4	0.049	0.35	-9999	-0.94	11	11
FOXM1B/HNF6	0.024	0.37	-9999	-1.1	11	11
FOS	-0.19	0.66	-9999	-1.2	107	107
SP1	0.014	0.006	-9999	-10000	0	0
CDC25B	0.048	0.35	-9999	-0.95	11	11
response to radiation	0.015	0.034	-9999	-10000	0	0
CENPB	0.049	0.35	-9999	-0.94	11	11
CENPA	0.041	0.36	-9999	-0.98	12	12
NEK2	0.039	0.36	-9999	-0.98	12	12
HIST1H2BA	0.04	0.35	-9999	-0.95	11	11
CCNA2	0.008	0.051	-9999	-0.33	9	9
EP300	0.013	0	-9999	-10000	0	0
CCNB1/CDK1	0.037	0.37	-9999	-1.1	11	11
CCNB2	0.045	0.36	-9999	-0.98	11	11
CCNB1	0.044	0.36	-9999	-0.99	11	11
ETV5	0.048	0.35	-9999	-0.94	12	12
ESR1	0	0.43	-9999	-1.1	27	27
CCND1	0.037	0.34	-9999	-0.9	10	10
GSK3A	0.03	0.031	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	0.036	0.052	-9999	-10000	0	0
CDK2	0.016	0.01	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.018	0.041	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.12	0.23	-9999	-0.91	16	16
GAS1	-0.13	0.62	-9999	-1.2	86	86
MMP2	0.042	0.37	-9999	-1.1	13	13
RB1/FOXM1C	0.045	0.34	-9999	-0.93	11	11
CREBBP	0.013	0	-9999	-10000	0	0

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.01	0.085	-10000	0	-0.77	5	5
HDAC1	0.002	0.008	-10000	0	-10000	0	0
AES	0.012	0.002	-10000	0	-10000	0	0
FBXW11	0.013	0	-10000	0	-10000	0	0
DTX1	-0.002	0.11	-10000	0	-0.85	7	7
LRP6/FZD1	0	0	-10000	0	-10000	0	0
TLE1	0.008	0.06	-10000	0	-0.85	2	2
AP1	-0.15	0.27	-10000	0	-0.5	134	134
NCSTN	0.013	0	-10000	0	-10000	0	0
ADAM10	0.002	0.095	-10000	0	-0.85	5	5
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.039	0.054	-10000	0	-10000	0	0
NICD/RBPSUH	-0.009	0.084	-10000	0	-0.77	5	5
WIF1	-0.034	0.1	-10000	0	-0.31	50	50
NOTCH1	-0.01	0.086	-10000	0	-0.79	5	5
PSENEN	0.013	0	-10000	0	-10000	0	0
KREMEN2	-0.011	0.085	-10000	0	-10000	0	0
DKK1	-0.041	0.13	-10000	0	-0.33	64	64
beta catenin/beta TrCP1	0.036	0.039	-10000	0	-10000	0	0
APH1B	0.013	0	-10000	0	-10000	0	0
APH1A	0.013	0	-10000	0	-10000	0	0
AXIN1	0.002	0.029	-10000	0	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	0.003	0.04	-10000	0	-0.36	2	2
PSEN1	0.013	0	-10000	0	-10000	0	0
FOS	-0.21	0.38	-10000	0	-0.85	106	106
JUN	-0.18	0.36	-10000	0	-0.85	93	93
MAP3K7	0.012	0.003	-10000	0	-10000	0	0
CTNNB1	0.03	0.042	0.24	12	-10000	0	12
MAPK3	0.013	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.039	0.12	-10000	0	-0.6	17	17
HNF1A	0.01	0.043	-10000	0	-0.85	1	1
CTBP1	0.012	0.002	-10000	0	-10000	0	0
MYC	-0.012	0.24	-10000	0	-1.5	10	10
NKD1	-0.017	0.15	-10000	0	-0.75	16	16
FZD1	0.013	0	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.017	0.1	-10000	0	-0.59	12	12
apoptosis	-0.15	0.26	-10000	0	-0.5	134	134
Delta 1/NOTCHprecursor	-0.009	0.081	-10000	0	-0.74	5	5
DLL1	0.012	0.016	-10000	0	-0.31	1	1
PPARD	0.024	0.016	-10000	0	-10000	0	0
Gamma Secretase	0	0	-10000	0	-10000	0	0
APC	0.002	0.029	-10000	0	-10000	0	0
DVL1	0	0.002	-10000	0	-10000	0	0
CSNK2A1	0.013	0.002	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.003	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.038	0.083	-10000	0	-0.65	2	2
LRP6	0.013	0	-10000	0	-10000	0	0
CSNK1A1	0.013	0.002	-10000	0	-10000	0	0
NLK	0.015	0.007	-10000	0	-10000	0	0
CCND1	0.018	0.045	-10000	0	-10000	0	0
WNT1	0.009	0.023	-10000	0	-0.31	2	2
Axin1/APC/beta catenin	0.046	0.035	-10000	0	-10000	0	0
DKK2	-0.031	0.18	-10000	0	-0.65	27	27
NOTCH1 precursor/DVL1	-0.005	0.073	-10000	0	-0.66	5	5
GSK3B	0.013	0.001	-10000	0	-10000	0	0
FRAT1	0.012	0.001	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.018	0.1	-10000	0	-0.6	12	12
PPP2R5D	0.013	0.068	0.38	13	-10000	0	13
MAPK1	0.013	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.017	0.044	-10000	0	-10000	0	0
RBPJ	0.012	0.016	-10000	0	-0.31	1	1
CREBBP	0.016	0.004	-10000	0	-10000	0	0

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	0.005	0.074	-10000	0	-0.37	5	5
CaM/Ca2+	0	0	-10000	0	-10000	0	0
AKT1	0.013	0	-10000	0	-10000	0	0
AKT2	0.013	0	-10000	0	-10000	0	0
STXBP4	0.013	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.036	0.075	0.23	7	-0.28	9	16
YWHAZ	0.013	0	-10000	0	-10000	0	0
CALM1	0.013	0	-10000	0	-10000	0	0
YWHAQ	0.013	0	-10000	0	-10000	0	0
TBC1D4	-0.054	0.22	-10000	0	-0.66	47	47
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.013	0	-10000	0	-10000	0	0
YWHAB	0.013	0	-10000	0	-10000	0	0
SNARE/Synip	0	0	-10000	0	-10000	0	0
YWHAG	0.013	0	-10000	0	-10000	0	0
ASIP	-0.023	0.1	-10000	0	-0.31	44	44
PRKCI	0.013	0	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0	0	-10000	0	-10000	0	0
RHOQ	0.013	0	-10000	0	-10000	0	0
GYS1	0.034	0	-10000	0	-10000	0	0
PRKCZ	0.013	0	-10000	0	-10000	0	0
TRIP10	0.013	0	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-10000	0	-10000	0	0
AS160/14-3-3	-0.035	0.099	-10000	0	-10000	0	0
VAMP2	0.013	0	-10000	0	-10000	0	0
SLC2A4	0.037	0.079	-10000	0	-0.31	9	9
STX4	0.013	0	-10000	0	-10000	0	0
GSK3B	0.027	0	-10000	0	-10000	0	0
SFN	-0.21	0.19	-10000	0	-0.34	265	265
LNPEP	-0.006	0.13	-10000	0	-0.85	9	9
YWHAE	0.013	0	-10000	0	-10000	0	0

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0	0	-9999	-10000	0	0
PRKCZ	0.013	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
ERC1	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.031	0.071	-9999	-0.32	7	7
IRAK/TOLLIP	0.029	0.004	-9999	-10000	0	0
IKBKB	0.013	0	-9999	-10000	0	0
IKBKG	0.013	0	-9999	-10000	0	0
IL1 alpha/IL1R2	-0.13	0.26	-9999	-0.7	65	65
IL1A	-0.06	0.24	-9999	-0.81	36	36
IL1B	-0.036	0.19	-9999	-0.67	34	34
IRAK/TRAF6/p62/Atypical PKCs	-0.001	0.022	-9999	-0.45	1	1
IL1R2	-0.089	0.25	-9999	-0.62	66	66
IL1R1	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.026	0.059	-9999	-10000	0	0
TOLLIP	0.013	0	-9999	-10000	0	0
TICAM2	0.002	0.095	-9999	-0.85	5	5
MAP3K3	0.013	0	-9999	-10000	0	0
TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
IKK complex/ELKS	0.067	0.022	-9999	-10000	0	0
JUN	-0.07	0.21	-9999	-0.44	98	98
MAP3K7	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.069	0.14	-9999	-0.5	34	34
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.079	0.15	-9999	-0.53	33	33
PIK3R1	0.013	0	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.071	0.14	-9999	-0.5	33	33
IL1 beta fragment/IL1R1/IL1RAP	-0.082	0.16	-9999	-0.56	33	33
NFKB1	0.013	0	-9999	-10000	0	0
MAPK8	0.029	0.08	-9999	-0.48	9	9
IRAK1	0.023	0.004	-9999	-10000	0	0
IL1RN/IL1R1	-0.042	0.11	-9999	-0.66	8	8
IRAK4	0.013	0	-9999	-10000	0	0
PRKCI	0.013	0	-9999	-10000	0	0
TRAF6	0.011	0.043	-9999	-0.85	1	1
PI3K	-0.002	0.032	-9999	-0.66	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.004	0.09	-9999	-0.35	7	7
CHUK	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.082	0.16	-9999	-0.56	33	33
IL1 beta/IL1R2	-0.11	0.24	-9999	-0.64	64	64
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.001	0.023	-9999	-0.46	1	1
NF kappa B1 p50/RelA	-0.059	0.12	-9999	-0.58	7	7
IRAK3	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.074	0.15	-9999	-0.51	38	38
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.019	0.11	-9999	-0.35	33	33
IL1 alpha/IL1R1/IL1RAP	-0.09	0.16	-9999	-0.58	33	33
RELA	0.013	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
SQSTM1	0.013	0	-9999	-10000	0	0
MYD88	0.013	0	-9999	-10000	0	0
IRAK/TRAF6/MEKK3	-0.001	0.024	-9999	-0.49	1	1
IL1RAP	-0.076	0.15	-9999	-10000	0	0
UBE2N	0.013	0	-9999	-10000	0	0
IRAK/TRAF6	-0.057	0.12	-9999	-0.52	11	11
CASP1	0.006	0.066	-9999	-0.53	5	5
IL1RN/IL1R2	-0.12	0.22	-9999	-0.63	53	53
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.074	0.15	-9999	-0.52	33	33
TMEM189-UBE2V1	0.004	0.006	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.007	0.081	-9999	-0.34	3	3
PIK3CA	0.011	0.043	-9999	-0.85	1	1
IL1RN	-0.052	0.16	-9999	-0.85	8	8
TRAF6/TAK1/TAB1/TAB2	-0.001	0.024	-9999	-0.48	1	1
MAP2K6	0.025	0.065	-9999	-0.46	7	7

×

LPA4-mediated signaling events

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
ADCY4	0.017	0.051	-9999	-0.58	3	3
ADCY5	-0.064	0.21	-9999	-0.58	57	57
ADCY6	0.017	0.051	-9999	-0.58	3	3
ADCY7	0.017	0.051	-9999	-0.58	3	3
ADCY1	0.01	0.078	-9999	-0.6	6	6
ADCY2	-0.041	0.18	-9999	-0.59	38	38
ADCY3	0.017	0.051	-9999	-0.58	3	3
ADCY8	-0.12	0.099	-9999	-0.73	3	3
PRKCE	0.007	0.058	-9999	-0.67	3	3
ADCY9	0.017	0.051	-9999	-0.58	3	3
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.056	0.1	-9999	-0.45	13	13

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.05	0.14	-9999	-0.45	45	45
TC10/GTP	-0.002	0.031	-9999	-0.44	2	2
Insulin Receptor/Insulin/IRS1/Shp2	-0.056	0.16	-9999	-0.54	43	43
HRAS	0.012	0.023	-9999	-0.31	2	2
APS homodimer	0.012	0.016	-9999	-0.31	1	1
GRB14	-0.019	0.16	-9999	-0.85	15	15
FOXO3	-0.021	0.098	-9999	-0.72	7	7
AKT1	-0.011	0.16	-9999	-0.78	1	1
INSR	0.015	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.013	0	-9999	-10000	0	0
SORBS1	0.009	0.06	-9999	-0.85	2	2
CRK	0.013	0	-9999	-10000	0	0
PTPN1	0.038	0	-9999	-10000	0	0
CAV1	-0.041	0.18	-9999	-0.5	54	54
CBL/APS/CAP/Crk-II/C3G	-0.003	0.034	-9999	-0.48	2	2
Insulin Receptor/Insulin/IRS1/NCK2	-0.056	0.16	-9999	-0.54	43	43
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.05	0.14	-9999	-0.47	44	44
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.006	0.1	-9999	-10000	0	0
RPS6KB1	0	0.15	-9999	-0.69	1	1
PARD6A	0.013	0	-9999	-10000	0	0
CBL	0.013	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	0.013	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.054	0.13	-9999	-0.67	1	1
HRAS/GTP	-0.047	0.12	-9999	-0.52	2	2
Insulin Receptor	0.015	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.052	0.15	-9999	-0.5	43	43
PRKCI	-0.014	0.035	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.063	0.16	-9999	-0.44	59	59
SHC1	0.013	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0	0	-9999	-10000	0	0
PI3K	-0.051	0.15	-9999	-0.48	44	44
NCK2	0.013	0	-9999	-10000	0	0
RHOQ	0.013	0	-9999	-10000	0	0
mol:H2O2	0	0	-9999	-10000	0	0
HRAS/GDP	-0.001	0.015	-9999	-10000	0	0
AKT2	-0.011	0.16	-9999	-0.43	16	16
PRKCZ	-0.014	0.035	-9999	-10000	0	0
SH2B2	0.012	0.016	-9999	-0.31	1	1
SHC/SHIP	-0.026	0.16	-9999	-0.48	43	43
F2RL2	-0.082	0.15	-9999	-0.32	118	118
TRIP10	0.013	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	0.013	0	-9999	-10000	0	0
RASA1	0.013	0	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	-0.003	0.037	-9999	-0.52	2	2
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0	0	-9999	-10000	0	0
INPP5D	-0.036	0.17	-9999	-0.51	43	43
SOS1	0.013	0	-9999	-10000	0	0
SGK1	-0.022	0.14	-9999	-1.1	7	7
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.013	0	-9999	-10000	0	0
IRS1	-0.078	0.26	-9999	-0.85	43	43
p62DOK/RasGAP	0	0	-9999	-10000	0	0
INS	0.003	0	-9999	-10000	0	0
mol:PI-3-4-P2	-0.035	0.16	-9999	-0.5	43	43
GRB2	0.013	0	-9999	-10000	0	0
EIF4EBP1	-0.002	0.15	-9999	-0.55	3	3
PTPRA	0.015	0	-9999	-10000	0	0
PIK3CA	0.011	0.043	-9999	-0.85	1	1
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0.011	0.043	-9999	-0.85	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	-0.004	0.12	-9999	-0.34	43	43
Insulin Receptor/Insulin/IRS1	-0.057	0.17	-9999	-0.54	43	43
Insulin Receptor/Insulin/IRS3	0	0	-9999	-10000	0	0
Par3/Par6	-0.036	0.059	-9999	-0.49	1	1

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	-0.17	0.35	-9999	-0.85	86	86
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.012	0.016	-9999	-0.31	1	1
TCEB1	0.013	0	-9999	-10000	0	0
HIF1A/p53	0.029	0.023	-9999	-10000	0	0
HIF1A	0.022	0.024	-9999	-10000	0	0
COPS5	0.013	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	-0.003	0.034	-9999	-0.48	2	2
FIH (dimer)	0.013	0	-9999	-10000	0	0
CDKN2A	-0.12	0.16	-9999	-0.31	169	169
ARNT/IPAS	-0.14	0.27	-9999	-0.66	86	86
HIF1AN	0.013	0	-9999	-10000	0	0
GNB2L1	0.013	0	-9999	-10000	0	0
HIF1A/ARNT	0.029	0.023	-9999	-10000	0	0
CUL2	0.013	0	-9999	-10000	0	0
OS9	0.013	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	0	0.008	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.029	0.023	-9999	-10000	0	0
PHD1-3/OS9	-0.018	0.084	-9999	-0.52	10	10
HIF1A/RACK1/Elongin B/Elongin C	-0.002	0.014	-9999	-10000	0	0
VHL	0.009	0.06	-9999	-0.85	2	2
HSP90AA1	0.013	0	-9999	-10000	0	0
HIF1A/JAB1	0.029	0.023	-9999	-10000	0	0
EGLN3	-0.022	0.15	-9999	-0.5	28	28
EGLN2	0.013	0	-9999	-10000	0	0
EGLN1	0.013	0	-9999	-10000	0	0
TP53	0.013	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.035	0.044	-9999	-0.59	2	2
ARNT	0.013	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.013	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.03	0.073	-9999	-10000	0	0

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.06	0.16	-10000	0	-0.5	49	49
MAPK9	0.009	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.008	0.055	-10000	0	-10000	0	0
GNB1/GNG2	0	0	-10000	0	-10000	0	0
GNB1	0.013	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	0.009	0	-10000	0	-10000	0	0
Gs family/GTP	-0.065	0.18	-10000	0	-0.54	49	49
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	0.014	0.039	0.12	49	-10000	0	49
GNAL	-0.09	0.28	-10000	0	-0.85	49	49
GNG2	0.013	0	-10000	0	-10000	0	0
CRH	-0.014	0.08	-10000	0	-0.31	27	27
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.006	0.041	-10000	0	-0.47	3	3
MAPK11	0.009	0	-10000	0	-10000	0	0

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	0.002	0.1	0.56	11	-10000	0	11
PI3K Class IB/PDE3B	-0.002	0.1	-10000	0	-0.56	11	11
PDE3B	-0.002	0.1	-10000	0	-0.56	11	11

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.024	0	-10000	0	-10000	0	0
MAP4K4	-0.004	0.15	-10000	0	-0.72	10	10
BAG4	0.011	0.043	-10000	0	-0.85	1	1
PKC zeta/ceramide	-0.017	0.04	-10000	0	-10000	0	0
NFKBIA	0.013	0	-10000	0	-10000	0	0
BIRC3	-0.038	0.2	-10000	0	-0.69	30	30
BAX	-0.005	0.019	-10000	0	-10000	0	0
RIPK1	0.013	0	-10000	0	-10000	0	0
AKT1	0.023	0.009	-10000	0	-10000	0	0
BAD	-0.017	0.041	-10000	0	-10000	0	0
SMPD1	-0.006	0.098	-10000	0	-0.27	47	47
RB1	-0.017	0.041	-10000	0	-10000	0	0
FADD/Caspase 8	0.008	0.14	-10000	0	-0.68	10	10
MAP2K4	-0.008	0.038	-10000	0	-10000	0	0
NSMAF	0.013	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.01	0.048	-10000	0	-0.59	1	1
EGF	-0.11	0.3	-10000	0	-0.8	61	61
mol:ceramide	-0.028	0.043	-10000	0	-10000	0	0
MADD	0.013	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.023	0.034	-10000	0	-0.66	1	1
ASAH1	0.011	0.043	-10000	0	-0.85	1	1
negative regulation of cell cycle	-0.017	0.04	-10000	0	-10000	0	0
cell proliferation	-0.097	0.17	-10000	0	-0.41	89	89
BID	-0.018	0.093	-10000	0	-0.41	10	10
MAP3K1	-0.017	0.041	-10000	0	-10000	0	0
EIF2A	0	0.037	-10000	0	-10000	0	0
TRADD	0.013	0	-10000	0	-10000	0	0
CRADD	0.013	0	-10000	0	-10000	0	0
MAPK3	0.003	0.045	-10000	0	-0.54	1	1
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.003	0.045	-10000	0	-0.54	1	1
Cathepsin D/ceramide	-0.017	0.04	-10000	0	-10000	0	0
FADD	-0.004	0.15	-10000	0	-0.72	10	10
KSR1	-0.018	0.05	-10000	0	-0.63	1	1
MAPK8	-0.005	0.048	-10000	0	-0.35	3	3
PRKRA	-0.017	0.041	-10000	0	-10000	0	0
PDGFA	0.013	0	-10000	0	-10000	0	0
TRAF2	0.013	0	-10000	0	-10000	0	0
IGF1	-0.18	0.36	-10000	0	-0.82	94	94
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.028	0.043	-10000	0	-10000	0	0
CTSD	0.013	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	-0.084	0.19	-10000	0	-0.44	89	89
PRKCD	0.013	0	-10000	0	-10000	0	0
PRKCZ	0.013	0	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.023	0.034	-10000	0	-0.66	1	1
RelA/NF kappa B1	0	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.013	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.013	0.16	-10000	0	-0.77	10	10
TNFR1A/BAG4/TNF-alpha	-0.069	0.18	-10000	0	-0.57	48	48
mol:Sphingosine-1-phosphate	0.024	0	-10000	0	-10000	0	0
MAP2K1	-0.001	0.046	-10000	0	-0.55	1	1
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.013	0	-10000	0	-10000	0	0
CYCS	0.002	0.049	0.18	19	-10000	0	19
TNFRSF1A	0.013	0	-10000	0	-10000	0	0
NFKB1	0.013	0	-10000	0	-10000	0	0
TNFR1A/BAG4	-0.002	0.032	-10000	0	-0.66	1	1
EIF2AK2	-0.008	0.038	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.068	0.18	-10000	0	-0.57	47	47
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.015	0.081	-10000	0	-0.34	10	10
MAP2K2	-0.001	0.046	-10000	0	-0.55	1	1
SMPD3	-0.014	0.12	-10000	0	-0.31	53	53
TNF	-0.091	0.28	-10000	0	-0.79	53	53
PKC zeta/PAR4	0	0	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	0.021	0.11	0.28	55	-10000	0	55
NF kappa B1/RelA/I kappa B alpha	0	0	-10000	0	-10000	0	0
AIFM1	0.002	0.05	0.18	19	-10000	0	19
BCL2	-0.042	0.21	-10000	0	-0.85	26	26

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.013	0	-9999	-10000	0	0
HDAC4	0.013	0	-9999	-10000	0	0
induction of apoptosis	0	0	-9999	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.022	0.005	-9999	-10000	0	0
CDKN1A	-0.008	0.039	-9999	-10000	0	0
KAT2B	0.013	0	-9999	-10000	0	0
BAX	0.013	0	-9999	-10000	0	0
FOXO3	0	0	-9999	-10000	0	0
FOXO1	0.013	0	-9999	-10000	0	0
FOXO4	0.024	0	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
XRCC6	0.013	0	-9999	-10000	0	0
TAT	0.008	0.017	-9999	-0.31	1	1
mol:Lysophosphatidic acid	0	0	-9999	-10000	0	0
MYOD1	0.011	0.021	-9999	-10000	0	0
PPARGC1A	-0.36	0.43	-9999	-0.85	178	178
FHL2	-0.057	0.24	-9999	-0.85	33	33
response to nutrient levels	0	0	-9999	-10000	0	0
KU70/SIRT1	0.002	0.012	-9999	-10000	0	0
HIST2H4A	0.022	0.005	-9999	-10000	0	0
SIRT1/FOXO3a	0.002	0.009	-9999	-10000	0	0
SIRT1	0.003	0.013	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
SIRT1/MEF2D/HDAC4	0.003	0.012	-9999	-10000	0	0
SIRT1/Histone H1b	-0.005	0.047	-9999	-0.32	8	8
apoptosis	-0.002	0.012	-9999	-10000	0	0
SIRT1/PGC1A	-0.25	0.29	-9999	-0.58	178	178
p53/SIRT1	0.007	0.035	-9999	-10000	0	0
SIRT1/FOXO4	0.003	0.013	-9999	-10000	0	0
FOXO1/FHL2/SIRT1	-0.04	0.14	-9999	-0.53	33	33
HIST1H1E	0.014	0.057	-9999	-0.37	8	8
SIRT1/p300	0.002	0.012	-9999	-10000	0	0
muscle cell differentiation	-0.001	0.019	-9999	-10000	0	0
TP53	0.003	0.013	-9999	-10000	0	0
KU70/SIRT1/BAX	0.003	0.012	-9999	-10000	0	0
CREBBP	0.013	0	-9999	-10000	0	0
MEF2D	0.013	0	-9999	-10000	0	0
HIV-1 Tat/SIRT1	0.002	0.015	-9999	-10000	0	0
ACSS2	0.022	0.005	-9999	-10000	0	0
SIRT1/PCAF/MYOD	0.001	0.019	-9999	-10000	0	0

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.013	0	-9999	-10000	0	0
SPHK1	0.007	0.045	-9999	-0.31	8	8
GNAI2	0.013	0	-9999	-10000	0	0
mol:S1P	0.022	0.015	-9999	-10000	0	0
GNAO1	-0.015	0.15	-9999	-0.72	16	16
mol:Sphinganine-1-P	0.02	0.031	-9999	-10000	0	0
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	-0.001	0.012	-9999	-10000	0	0
GNAI3	0.013	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
S1PR3	0.013	0	-9999	-10000	0	0
S1PR2	0.012	0.023	-9999	-0.31	2	2
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.001	0.01	-9999	-10000	0	0
S1PR5	0.009	0.036	-9999	-0.31	5	5
S1PR4	0.01	0.032	-9999	-0.31	4	4
GNAI1	0.013	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.003	0.017	-9999	-10000	0	0
S1P/S1P3/Gq	-0.044	0.15	-9999	-0.31	95	95
S1P/S1P4/Gi	0.032	0.064	-9999	-0.32	12	12
GNAQ	0.013	0	-9999	-10000	0	0
GNAZ	0.013	0	-9999	-10000	0	0
GNA14	-0.18	0.36	-9999	-0.85	92	92
GNA15	-0.012	0.094	-9999	-0.33	30	30
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
GNA11	0.005	0.085	-9999	-0.85	4	4
ABCC1	0.013	0	-9999	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.013	0	-9999	-10000	0	0
ITGB7	-0.024	0.15	-9999	-0.52	28	28
ITGA4	0.007	0.045	-9999	-0.31	8	8
alpha4/beta7 Integrin	-0.03	0.12	-9999	-0.64	12	12
alpha4/beta1 Integrin	-0.004	0.028	-9999	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.013	0	-10000	0	-10000	0	0
NFATC1	0.048	0.054	-10000	0	-0.39	5	5
NFATC2	-0.012	0.088	-10000	0	-0.29	16	16
NFATC3	0.018	0.012	-10000	0	-10000	0	0
YWHAE	0.013	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.008	0.094	-10000	0	-0.3	26	26
Exportin 1/Ran/NUP214	0	0	-10000	0	-10000	0	0
mol:DAG	-0.002	0.004	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.027	0.09	-10000	0	-0.57	5	5
BCL2/BAX	-0.042	0.16	-10000	0	-0.66	26	26
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.002	0.007	-10000	0	-10000	0	0
CaM/Ca2+	-0.002	0.007	-10000	0	-10000	0	0
BAX	0.013	0	-10000	0	-10000	0	0
MAPK14	0.01	0.006	-10000	0	-10000	0	0
BAD	0.013	0	-10000	0	-10000	0	0
CABIN1/MEF2D	0.012	0.089	-10000	0	-0.53	3	3
Calcineurin A alpha-beta B1/BCL2	-0.042	0.21	-10000	0	-0.85	26	26
FKBP8	0.013	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.012	0.088	0.52	3	-10000	0	3
KPNB1	0.013	0	-10000	0	-10000	0	0
KPNA2	0.013	0	-10000	0	-10000	0	0
XPO1	0.013	0.001	-10000	0	-10000	0	0
SFN	-0.21	0.19	-10000	0	-0.34	265	265
MAP3K8	-0.003	0.1	-10000	0	-0.85	6	6
NFAT4/CK1 alpha	0	0	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.11	0.16	-10000	0	-0.34	123	123
CABIN1	0.008	0.094	-10000	0	-0.31	26	26
CALM1	0.01	0.006	-10000	0	-10000	0	0
RAN	0.013	0.001	-10000	0	-10000	0	0
MAP3K1	0.013	0	-10000	0	-10000	0	0
CAMK4	-0.003	0.097	-10000	0	-0.48	13	13
mol:Ca2+	-0.005	0.01	-10000	0	-10000	0	0
MAPK3	0.013	0	-10000	0	-10000	0	0
YWHAH	0.013	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0	0	-10000	0	-10000	0	0
YWHAB	0.013	0	-10000	0	-10000	0	0
MAPK8	0.003	0.074	-10000	0	-0.85	3	3
MAPK9	0.013	0	-10000	0	-10000	0	0
YWHAG	0.013	0	-10000	0	-10000	0	0
FKBP1A	0.013	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	-0.007	0.044	-10000	0	-10000	0	0
PRKCH	0.013	0	-10000	0	-10000	0	0
CABIN1/Cbp/p300	-0.003	0.004	-10000	0	-10000	0	0
CASP3	0.01	0.006	-10000	0	-10000	0	0
PIM1	0.013	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0	-10000	0	-10000	0	0
apoptosis	-0.013	0.049	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	-0.006	0.049	-10000	0	-10000	0	0
PRKCB	-0.023	0.11	-10000	0	-0.34	42	42
PRKCE	0.007	0.074	-10000	0	-0.85	3	3
JNK2/NFAT4	0.021	0.014	-10000	0	-10000	0	0
BAD/BCL-XL	0	0	-10000	0	-10000	0	0
PRKCD	0.013	0	-10000	0	-10000	0	0
NUP214	0.013	0.001	-10000	0	-10000	0	0
PRKCZ	0.01	0.006	-10000	0	-10000	0	0
PRKCA	-0.038	0.2	-10000	0	-0.85	24	24
PRKCG	0.005	0.023	-10000	0	-0.31	2	2
PRKCQ	0	0.1	-10000	0	-0.85	6	6
FKBP38/BCL2	-0.042	0.16	-10000	0	-0.66	26	26
EP300	0.009	0.007	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.013	0	-10000	0	-10000	0	0
NFATc/JNK1	0.038	0.07	-10000	0	-0.41	3	3
CaM/Ca2+/FKBP38	0	0	-10000	0	-10000	0	0
FKBP12/FK506	0	0	-10000	0	-10000	0	0
CSNK1A1	0.015	0.01	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.01	0.063	-10000	0	-0.59	4	4
NFATc/ERK1	0.053	0.051	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.026	0.088	-10000	0	-0.56	5	5
NR4A1	-0.19	0.37	-10000	0	-0.75	123	123
GSK3B	0.01	0.006	-10000	0	-10000	0	0
positive T cell selection	0.018	0.012	-10000	0	-10000	0	0
NFAT1/CK1 alpha	-0.032	0.057	-10000	0	-0.48	2	2
RCH1/ KPNB1	0	0	-10000	0	-10000	0	0
YWHAQ	0.013	0	-10000	0	-10000	0	0
PRKACA	0.01	0.006	-10000	0	-10000	0	0
AKAP5	0.013	0	-10000	0	-10000	0	0
MEF2D	0.009	0.007	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.013	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.042	0.058	-10000	0	-10000	0	0
CREBBP	0.009	0.007	-10000	0	-10000	0	0
BCL2	-0.042	0.21	-10000	0	-0.85	26	26

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.013	0.12	-10000	0	-0.59	9	9
UGCG	-0.034	0.16	-10000	0	-0.82	15	15
AKT1/mTOR/p70S6K/Hsp90/TERT	0.025	0.13	-10000	0	-0.41	14	14
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.013	0.16	-10000	0	-0.81	15	15
mol:DAG	0	0.004	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.054	0.13	-10000	0	-0.46	25	25
FRAP1	0.01	0.19	-10000	0	-0.54	25	25
FOXO3	0.025	0.16	-10000	0	-0.61	13	13
AKT1	0.017	0.17	-10000	0	-0.65	14	14
GAB2	0.013	0.004	-10000	0	-10000	0	0
SMPD1	-0.005	0.022	-10000	0	-10000	0	0
SGMS1	-0.005	0.022	-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	0.021	0.031	-10000	0	-0.58	1	1
CALM1	0.013	0	-10000	0	-10000	0	0
cell proliferation	0.005	0.15	-10000	0	-0.47	23	23
EIF3A	0.013	0	-10000	0	-10000	0	0
PI3K	0.022	0.035	-10000	0	-0.66	1	1
RPS6KB1	0.017	0.042	-10000	0	-10000	0	0
mol:sphingomyelin	0	0.004	-10000	0	-10000	0	0
natural killer cell activation	0	0.003	-10000	0	-0.012	6	6
JAK3	-0.06	0.14	-10000	0	-0.31	94	94
PIK3R1	0.015	0.005	-10000	0	-10000	0	0
JAK1	0.015	0.005	-10000	0	-10000	0	0
NFKB1	0.013	0	-10000	0	-10000	0	0
MYC	0.013	0.21	-10000	0	-0.91	15	15
MYB	-0.017	0.2	-10000	0	-1.4	9	9
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.013	0.16	-10000	0	-0.62	17	17
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.031	0.038	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.013	0.16	-10000	0	-0.59	17	17
Rac1/GDP	0.026	0.029	-10000	0	-0.53	1	1
T cell proliferation	0.022	0.15	-10000	0	-0.55	16	16
SHC1	0.013	0.004	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.004	0.011	-10000	0	-0.054	13	13
PRKCZ	0.021	0.15	-10000	0	-0.58	16	16
NF kappa B1 p50/RelA	-0.053	0.13	-10000	0	-0.51	15	15
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.004	0.13	-10000	0	-0.63	10	10
HSP90AA1	0.013	0	-10000	0	-10000	0	0
RELA	0.013	0	-10000	0	-10000	0	0
IL2RA	-0.044	0.2	-10000	0	-0.85	20	20
IL2RB	-0.013	0.14	-10000	0	-0.85	9	9
TERT	0	0.032	-10000	0	-10000	0	0
E2F1	-0.005	0.077	-10000	0	-0.45	9	9
SOS1	0.013	0.004	-10000	0	-10000	0	0
RPS6	0.013	0	-10000	0	-10000	0	0
mol:cAMP	-0.002	0.005	0.026	13	-10000	0	13
PTPN11	0.013	0.004	-10000	0	-10000	0	0
IL2RG	-0.045	0.2	-10000	0	-0.85	20	20
actin cytoskeleton organization	0.022	0.15	-10000	0	-0.55	16	16
GRB2	0.013	0.004	-10000	0	-10000	0	0
IL2	0.007	0.007	-10000	0	-10000	0	0
PIK3CA	0.013	0.043	-10000	0	-0.85	1	1
Rac1/GTP	0.033	0.029	-10000	0	-0.51	1	1
LCK	-0.007	0.11	-10000	0	-0.44	20	20
BCL2	-0.015	0.27	-10000	0	-0.83	35	35

×

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

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
BAG4	0.011	0.043	-9999	-0.85	1	1
Caspase 8 (4 units)	-0.023	0.064	-9999	-10000	0	0
NEF	-0.012	0.056	-9999	-10000	0	0
NFKBIA	0.009	0.03	-9999	-10000	0	0
BIRC3	-0.005	0.2	-9999	-0.85	21	21
CYCS	-0.009	0.1	-9999	-0.4	5	5
RIPK1	0.013	0	-9999	-10000	0	0
CD247	-0.043	0.2	-9999	-0.8	22	22
MAP2K7	0.023	0.082	-9999	-0.32	2	2
protein ubiquitination	0.039	0.088	-9999	-10000	0	0
CRADD	0.013	0	-9999	-10000	0	0
DAXX	0.013	0	-9999	-10000	0	0
FAS	0.013	0	-9999	-10000	0	0
BID	-0.019	0.11	-9999	-0.42	5	5
NF-kappa-B/RelA/I kappa B alpha	-0.021	0.078	-9999	-0.34	21	21
TRADD	0.013	0	-9999	-10000	0	0
MAP3K5	0.011	0.043	-9999	-0.85	1	1
CFLAR	0.013	0	-9999	-10000	0	0
FADD	0.013	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.021	0.079	-9999	-0.35	21	21
MAPK8	0.027	0.088	-9999	-0.44	3	3
APAF1	0.013	0	-9999	-10000	0	0
TRAF1	0.013	0	-9999	-10000	0	0
TRAF2	0.013	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.008	0.1	-9999	-0.31	25	25
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.024	0.11	-9999	-0.37	10	10
CHUK	0.039	0.094	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.001	0.024	-9999	-0.48	1	1
TCRz/NEF	-0.064	0.19	-9999	-0.53	46	46
TNF	-0.091	0.28	-9999	-0.79	53	53
FASLG	-0.077	0.3	-9999	-0.87	46	46
NFKB1	0.009	0.03	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.069	0.18	-9999	-0.57	48	48
CASP6	-0.005	0.047	-9999	-10000	0	0
CASP7	0.028	0.17	-9999	-0.64	21	21
RELA	0.009	0.03	-9999	-10000	0	0
CASP2	0.013	0	-9999	-10000	0	0
CASP3	0.028	0.17	-9999	-0.64	21	21
TNFRSF1A	0.013	0	-9999	-10000	0	0
TNFR1A/BAG4	-0.002	0.032	-9999	-0.66	1	1
CASP8	0.013	0	-9999	-10000	0	0
CASP9	0.013	0	-9999	-10000	0	0
MAP3K14	0.032	0.1	-9999	-0.38	2	2
APAF-1/Caspase 9	-0.048	0.12	-9999	-0.54	21	21
BCL2	0.004	0.14	-9999	-0.42	28	28

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	0.033	0	-9999	-10000	0	0
epithelial cell differentiation	0	0	-9999	-10000	0	0
CYFIP2	0.013	0	-9999	-10000	0	0
ENAH	0.071	0.01	-9999	-10000	0	0
EGFR	0.003	0.095	-9999	-0.85	5	5
EPHA2	0.011	0.028	-9999	-0.31	3	3
MYO6	0.041	0	-9999	-10000	0	0
CTNNB1	0.013	0	-9999	-10000	0	0
ABI1/Sra1/Nap1	0	0	-9999	-10000	0	0
AQP5	-0.04	0.14	-9999	-0.61	22	22
CTNND1	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.04	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.038	0.074	-9999	-10000	0	0
EGF	-0.11	0.3	-9999	-0.8	61	61
NCKAP1	0.013	0	-9999	-10000	0	0
AQP3	-0.073	0.2	-9999	-0.61	49	49
cortical microtubule organization	0	0	-9999	-10000	0	0
GO:0000145	0.039	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0	0	-9999	-10000	0	0
MLLT4	0.013	0	-9999	-10000	0	0
ARF6/GDP	0	0.006	-9999	-10000	0	0
ARF6	0.013	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.001	0.011	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
VASP	0.051	0.024	-9999	-10000	0	0
PVRL2	0.013	0	-9999	-10000	0	0
ZYX	0.041	0	-9999	-10000	0	0
ARF6/GTP	-0.001	0.01	-9999	-10000	0	0
CDH1	0.013	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.067	0.16	-9999	-0.45	60	60
RhoA/GDP	0	0	-9999	-10000	0	0
actin cytoskeleton organization	0.047	0	-9999	-10000	0	0
IGF-1R heterotetramer	0.013	0	-9999	-10000	0	0
GIT1	0.013	0	-9999	-10000	0	0
IGF1R	0.013	0	-9999	-10000	0	0
IGF1	-0.18	0.36	-9999	-0.82	94	94
DIAPH1	0	0.002	-9999	-10000	0	0
Wnt receptor signaling pathway	0	0	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
RhoA/GTP	0	0.006	-9999	-10000	0	0
CTNNA1	0.013	0	-9999	-10000	0	0
VCL	0.048	0	-9999	-10000	0	0
EFNA1	0.013	0	-9999	-10000	0	0
LPP	0.044	0.043	-9999	-0.45	3	3
Ephrin A1/EPHA2	-0.001	0.008	-9999	-10000	0	0
SEC6/SEC8	0	0	-9999	-10000	0	0
MGAT3	-0.038	0.074	-9999	-10000	0	0
HGF/MET	-0.11	0.17	-9999	-0.5	62	62
HGF	-0.12	0.31	-9999	-0.85	62	62
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.033	0	-9999	-10000	0	0
actin cable formation	0.087	0.016	-9999	-10000	0	0
KIAA1543	0.047	0.024	-9999	-0.44	1	1
KIFC3	0.041	0	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
EXOC3	0.013	0	-9999	-10000	0	0
ACTN1	0.04	0.007	-9999	-10000	0	0
NCK1/GIT1	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
EXOC4	0.013	0	-9999	-10000	0	0
STX4	0.041	0	-9999	-10000	0	0
PIP5K1C	0.041	0	-9999	-10000	0	0
LIMA1	0.013	0	-9999	-10000	0	0
ABI1	0.013	0	-9999	-10000	0	0
ROCK1	0	0.005	-9999	-10000	0	0
adherens junction assembly	0.064	0.022	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.099	0.18	-9999	-0.45	89	89
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
MET	-0.12	0.16	-9999	-0.31	164	164
PLEKHA7	0.04	0.025	-9999	-0.47	1	1
mol:GTP	-0.001	0.011	-9999	-10000	0	0
establishment of epithelial cell apical/basal polarity	0.067	0	-9999	-10000	0	0
cortical actin cytoskeleton stabilization	0.033	0	-9999	-10000	0	0
regulation of cell-cell adhesion	0.047	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.033	0	-9999	-10000	0	0

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.014	0	-9999	-10000	0	0
ELF1	-0.008	0.1	-9999	-0.41	21	21
CCNA2	0.006	0.048	-9999	-0.31	9	9
PIK3CA	0.012	0.043	-9999	-0.85	1	1
JAK3	-0.061	0.14	-9999	-0.31	94	94
PIK3R1	0.014	0	-9999	-10000	0	0
JAK1	0.014	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.022	0.15	-9999	-0.6	15	15
SHC1	0.014	0	-9999	-10000	0	0
SP1	0.021	0	-9999	-10000	0	0
IL2RA	-0.035	0.24	-9999	-1	21	21
IL2RB	-0.014	0.14	-9999	-0.85	9	9
SOS1	0.014	0	-9999	-10000	0	0
IL2RG	-0.047	0.2	-9999	-0.85	20	20
G1/S transition of mitotic cell cycle	0.042	0.04	-9999	-0.62	1	1
PTPN11	0.014	0	-9999	-10000	0	0
CCND2	0.033	0	-9999	-10000	0	0
LCK	-0.009	0.11	-9999	-0.45	20	20
GRB2	0.014	0	-9999	-10000	0	0
IL2	0.005	0.006	-9999	-10000	0	0
CDK6	0.011	0.043	-9999	-0.85	1	1
CCND3	0.033	0.13	-9999	-0.64	7	7

×

Class I PI3K 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.001	0.031	0.31	1	-0.55	1	2
DAPP1	-0.058	0.14	-10000	0	-0.51	11	11
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.064	0.18	-10000	0	-0.5	27	27
mol:DAG	-0.008	0.098	-10000	0	-0.28	13	13
HRAS	0.013	0.023	-10000	0	-0.31	2	2
RAP1A	0.014	0.001	-10000	0	-10000	0	0
ARF5/GDP	0.023	0.036	-10000	0	-0.47	1	1
PLCG2	0.013	0	-10000	0	-10000	0	0
PLCG1	0.013	0	-10000	0	-10000	0	0
ARF5	0.013	0	-10000	0	-10000	0	0
mol:GTP	0	0.015	0.27	1	-10000	0	1
ARF1/GTP	0	0.022	0.29	1	-10000	0	1
RHOA	0.013	0	-10000	0	-10000	0	0
YES1	0.013	0	-10000	0	-10000	0	0
RAP1A/GTP	0	0.015	0.26	1	-10000	0	1
ADAP1	0	0.014	-10000	0	-10000	0	0
ARAP3	0	0.015	0.27	1	-10000	0	1
INPPL1	0.013	0	-10000	0	-10000	0	0
PREX1	0.013	0	-10000	0	-10000	0	0
ARHGEF6	0.013	0	-10000	0	-10000	0	0
ARHGEF7	0.013	0	-10000	0	-10000	0	0
ARF1	0.013	0	-10000	0	-10000	0	0
NRAS	0.014	0.001	-10000	0	-10000	0	0
FYN	0.013	0	-10000	0	-10000	0	0
ARF6	0.013	0	-10000	0	-10000	0	0
FGR	0.01	0.032	-10000	0	-0.31	4	4
mol:Ca2+	0.005	0.055	-10000	0	-10000	0	0
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	-0.17	0.16	-10000	0	-0.32	230	230
ZAP70	-0.025	0.17	-10000	0	-0.66	23	23
mol:IP3	0.002	0.073	-10000	0	-0.22	1	1
LYN	0.013	0	-10000	0	-10000	0	0
ARF1/GDP	0.023	0.036	-10000	0	-0.47	1	1
RhoA/GDP	-0.001	0.021	0.29	1	-10000	0	1
PDK1/Src/Hsp90	-0.002	0.029	-10000	0	-0.57	1	1
BLNK	0.013	0	-10000	0	-10000	0	0
actin cytoskeleton reorganization	0.039	0.039	-10000	0	-10000	0	0
SRC	0.012	0.016	-10000	0	-0.31	1	1
PLEKHA2	0.021	0.043	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
PTEN	-0.002	0.041	-10000	0	-0.83	1	1
HSP90AA1	0.013	0	-10000	0	-10000	0	0
ARF6/GTP	0	0.016	0.31	1	-10000	0	1
RhoA/GTP	0	0.014	0.26	1	-10000	0	1
Src family/SYK family/BLNK-LAT	-0.055	0.16	-10000	0	-0.63	11	11
BLK	-0.26	0.39	-10000	0	-0.78	143	143
PDPK1	0.011	0.043	-10000	0	-0.85	1	1
CYTH1	0	0.014	0.26	1	-10000	0	1
HCK	-0.008	0.08	-10000	0	-0.31	26	26
CYTH3	-0.001	0.031	0.26	1	-0.57	1	2
CYTH2	0	0.014	-10000	0	-10000	0	0
KRAS	0.014	0.001	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	-0.01	0.084	-10000	0	-0.63	7	7
SGK1	-0.011	0.095	0.24	1	-0.7	7	8
INPP5D	-0.005	0.075	-10000	0	-0.31	23	23
mol:GDP	0.016	0.038	-10000	0	-0.5	1	1
SOS1	0.013	0	-10000	0	-10000	0	0
SYK	0.013	0	-10000	0	-10000	0	0
ARF6/GDP	-0.001	0.021	0.3	1	-10000	0	1
mol:PI-3-4-5-P3	0	0.02	0.37	1	-10000	0	1
ARAP3/RAP1A/GTP	0	0.015	0.26	1	-10000	0	1
VAV1	-0.014	0.11	-10000	0	-0.37	29	29
mol:PI-3-4-P2	0.012	0.052	-10000	0	-10000	0	0
RAS family/GTP/PI3K Class I	0	0.007	-10000	0	-10000	0	0
PLEKHA1	0.021	0.043	-10000	0	-10000	0	0
Rac1/GDP	0.023	0.036	-10000	0	-0.47	1	1
LAT	0.004	0.086	-10000	0	-0.74	5	5
Rac1/GTP	-0.005	0.055	-10000	0	-0.62	1	1
ITK	-0.061	0.15	-10000	0	-0.46	52	52
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.019	0.13	-10000	0	-0.41	13	13
LCK	-0.009	0.11	-10000	0	-0.45	20	20
BTK	-0.013	0.062	0.26	1	-0.46	6	7

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	0.018	0.094	-10000	0	-0.47	10	10
ACTA1	0.01	0.11	-10000	0	-0.57	10	10
NUMA1	0.018	0.094	-10000	0	-0.47	10	10
SPTAN1	0.015	0.11	-10000	0	-0.56	10	10
LIMK1	0.015	0.11	-10000	0	-0.56	10	10
BIRC3	-0.038	0.2	-10000	0	-0.69	30	30
BIRC2	0.013	0	-10000	0	-10000	0	0
BAX	0.013	0	-10000	0	-10000	0	0
CASP10	-0.001	0.12	-10000	0	-0.59	13	13
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.013	0	-10000	0	-10000	0	0
PTK2	0.018	0.094	-10000	0	-0.47	10	10
DIABLO	0.013	0	-10000	0	-10000	0	0
apoptotic nuclear changes	0.015	0.11	-10000	0	-0.55	10	10
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.013	0	-10000	0	-10000	0	0
GSN	0.015	0.11	-10000	0	-0.57	10	10
MADD	0.013	0	-10000	0	-10000	0	0
TFAP2A	-0.057	0.23	-10000	0	-0.67	49	49
BID	-0.013	0.07	-10000	0	-0.32	10	10
MAP3K1	0.014	0.042	-10000	0	-0.19	7	7
TRADD	0.013	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	0.012	0.12	-10000	0	-0.59	9	9
CASP9	0.013	0	-10000	0	-10000	0	0
DNA repair	-0.016	0.052	-10000	0	-0.23	18	18
neuron apoptosis	0.023	0.016	-10000	0	-10000	0	0
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.021	0.11	-10000	0	-0.6	8	8
APAF1	0.013	0	-10000	0	-10000	0	0
CASP6	0.021	0.07	-10000	0	-0.49	4	4
TRAF2	0.013	0	-10000	0	-10000	0	0
ICAD/CAD	0.022	0.11	-10000	0	-0.6	8	8
CASP7	0.01	0.082	0.34	21	-10000	0	21
KRT18	0.016	0.019	-10000	0	-10000	0	0
apoptosis	0.028	0.1	-10000	0	-0.52	8	8
DFFA	0.015	0.11	-10000	0	-0.56	10	10
DFFB	0.015	0.11	-10000	0	-0.59	9	9
PARP1	0.016	0.052	0.23	18	-10000	0	18
actin filament polymerization	-0.023	0.1	0.56	8	-10000	0	8
TNF	-0.091	0.28	-10000	0	-0.79	53	53
CYCS	0.004	0.046	-10000	0	-0.23	10	10
SATB1	0.029	0.067	-10000	0	-0.46	4	4
SLK	0.015	0.11	-10000	0	-0.56	10	10
p15 BID/BAX	-0.004	0.062	-10000	0	-0.35	4	4
CASP2	0.006	0.12	-10000	0	-0.47	10	10
JNK cascade	-0.014	0.042	0.19	7	-10000	0	7
CASP3	0.007	0.12	0.25	8	-0.6	10	18
LMNB2	0.02	0.08	-10000	0	-0.39	4	4
RIPK1	0.013	0	-10000	0	-10000	0	0
CASP4	0.013	0	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	-0.03	0.12	-10000	0	-0.52	21	21
negative regulation of DNA binding	-0.056	0.22	-10000	0	-0.66	49	49
stress fiber formation	0.015	0.11	-10000	0	-0.55	10	10
GZMB	-0.014	0.14	-10000	0	-0.68	13	13
CASP1	0.015	0.035	-10000	0	-0.46	2	2
LMNB1	0.02	0.081	-10000	0	-0.39	4	4
APP	0.023	0.016	-10000	0	-10000	0	0
TNFRSF1A	0.013	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.012	0	-10000	0	-10000	0	0
VIM	0.022	0.098	0.26	18	-0.51	8	26
LMNA	0.02	0.08	-10000	0	-0.39	4	4
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.003	0.12	-10000	0	-0.5	10	10
LRDD	0.013	0	-10000	0	-10000	0	0
SREBF1	0.014	0.11	-10000	0	-0.62	8	8
APAF-1/Caspase 9	0.005	0.038	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0.018	0.093	-10000	0	-0.46	10	10
CFL2	0.022	0.11	-10000	0	-0.58	8	8
GAS2	0.009	0.13	-10000	0	-0.55	15	15
positive regulation of apoptosis	0.022	0.083	-10000	0	-0.38	4	4
PRF1	-0.002	0.11	-10000	0	-0.67	9	9

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	-0.004	0.12	-10000	0	-0.85	8	8
ANTXR2	0.011	0.043	-10000	0	-0.85	1	1
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.002	0.015	-10000	0	-0.1	9	9
monocyte activation	-0.045	0.16	-10000	0	-0.48	49	49
MAP2K2	-0.001	0.006	-10000	0	-10000	0	0
MAP2K1	-0.002	0.013	-10000	0	-10000	0	0
MAP2K7	-0.002	0.013	-10000	0	-10000	0	0
MAP2K6	-0.01	0.065	-10000	0	-0.53	6	6
CYAA	0.005	0.076	-10000	0	-0.5	9	9
MAP2K4	-0.002	0.013	-10000	0	-10000	0	0
IL1B	-0.027	0.14	-10000	0	-0.48	34	34
Channel	-0.012	0.079	-10000	0	-0.54	9	9
NLRP1	-0.004	0.038	-10000	0	-0.52	2	2
CALM1	0.013	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.003	0.018	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.002	0.015	0.1	9	-10000	0	9
MAPK3	-0.002	0.013	-10000	0	-10000	0	0
MAPK1	-0.002	0.013	-10000	0	-10000	0	0
PGR	-0.024	0.087	-10000	0	-0.47	12	12
PA/Cellular Receptors	-0.013	0.085	-10000	0	-0.58	9	9
apoptosis	-0.002	0.015	-10000	0	-0.1	9	9
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.005	0.076	-10000	0	-0.5	9	9
macrophage activation	0.019	0.014	-10000	0	-10000	0	0
TNF	-0.091	0.28	-10000	0	-0.79	53	53
VCAM1	-0.046	0.16	-10000	0	-0.48	49	49
platelet activation	-0.003	0.018	-10000	0	-10000	0	0
MAPKKK cascade	-0.014	0.022	0.12	6	-10000	0	6
IL18	-0.011	0.089	-10000	0	-0.43	12	12
negative regulation of macrophage activation	-0.002	0.015	-10000	0	-0.1	9	9
LEF	-0.002	0.015	-10000	0	-0.1	9	9
CASP1	-0.003	0.021	-10000	0	-0.12	11	11
mol:cAMP	-0.003	0.018	-10000	0	-10000	0	0
necrosis	-0.002	0.015	-10000	0	-0.1	9	9
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.011	0.075	-10000	0	-0.51	9	9
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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
HDAC1	0.013	0	-10000	0	-10000	0	0
HDAC3	0.013	0	-10000	0	-10000	0	0
VDR	0.012	0.016	-10000	0	-0.31	1	1
Cbp/p300/PCAF	0	0	-10000	0	-10000	0	0
EP300	0.013	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.034	0.058	-10000	0	-0.33	5	5
KAT2B	0.013	0	-10000	0	-10000	0	0
MAPK14	0.013	0	-10000	0	-10000	0	0
AKT1	0.011	0.081	0.24	4	-0.42	10	14
RAR alpha/9cRA/Cyclin H	-0.025	0.094	-10000	0	-0.39	24	24
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.03	0.064	-10000	0	-0.38	5	5
CDC2	0.001	0.001	-10000	0	-10000	0	0
response to UV	0.001	0.002	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.02	0.082	-10000	0	-0.68	3	3
NCOR2	0.013	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	-0.001	0.011	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA	-0.024	0.17	-10000	0	-0.64	25	25
NCOA2	-0.05	0.22	-10000	0	-0.85	30	30
NCOA3	0.013	0	-10000	0	-10000	0	0
NCOA1	0.013	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.012	0.016	-10000	0	-0.31	1	1
RARG	0.014	0.002	-10000	0	-10000	0	0
RAR gamma1/9cRA	0	0	-10000	0	-10000	0	0
MAPK3	0.014	0.002	-10000	0	-10000	0	0
MAPK1	0.013	0	-10000	0	-10000	0	0
MAPK8	0.008	0.074	-10000	0	-0.85	3	3
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.043	0.16	-10000	0	-0.66	24	24
RARA	0.006	0.085	-10000	0	-0.31	27	27
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.006	0.12	-10000	0	-0.51	11	11
PRKCA	-0.034	0.2	-10000	0	-0.85	24	24
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.035	0.17	-10000	0	-0.66	25	25
RXRG	-0.12	0.12	-10000	0	-0.54	27	27
RXRA	0.011	0.094	-10000	0	-0.35	24	24
RXRB	-0.002	0.11	-10000	0	-0.46	24	24
VDR/Vit D3/DNA	-0.001	0.011	-10000	0	-10000	0	0
RBP1	-0.001	0.1	-10000	0	-0.61	9	9
CRBP1/9-cic-RA	-0.01	0.076	-10000	0	-0.46	9	9
RARB	-0.006	0.13	-10000	0	-0.85	10	10
PRKCG	0.008	0.024	-10000	0	-0.31	2	2
MNAT1	0.013	0	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.032	0.18	-10000	0	-0.7	25	25
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.012	0.15	-10000	0	-0.55	25	25
proteasomal ubiquitin-dependent protein catabolic process	0.029	0.081	-10000	0	-0.43	5	5
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.035	0.17	-10000	0	-0.66	25	25
positive regulation of DNA binding	-0.024	0.089	-10000	0	-0.37	24	24
NRIP1	-0.033	0.16	-10000	0	-0.82	6	6
RXRs/RARs	-0.042	0.17	-10000	0	-0.66	25	25
RXRs/RXRs/DNA/9cRA	-0.055	0.16	-10000	0	-0.69	24	24
PRKACA	0.013	0	-10000	0	-10000	0	0
CDK7	0.013	0	-10000	0	-10000	0	0
TFIIH	0	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.012	0.046	-10000	0	-10000	0	0
CCNH	0.013	0	-10000	0	-10000	0	0
CREBBP	0.013	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	0	0	-10000	0	-10000	0	0

×

BARD1 signaling events

Figure S94. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S94. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	-0.031	0.14	-10000	0	-0.66	19	19
ATM	0.011	0.043	-10000	0	-0.85	1	1
UBE2D3	0.013	0	-10000	0	-10000	0	0
PRKDC	0.013	0	-10000	0	-10000	0	0
ATR	0.013	0	-10000	0	-10000	0	0
UBE2L3	0.013	0	-10000	0	-10000	0	0
FANCD2	0.026	0.024	-10000	0	-0.45	1	1
protein ubiquitination	-0.023	0.1	-10000	0	-0.48	20	20
XRCC5	0.013	0	-10000	0	-10000	0	0
XRCC6	0.013	0	-10000	0	-10000	0	0
M/R/N Complex	0	0	-10000	0	-10000	0	0
MRE11A	0.013	0	-10000	0	-10000	0	0
DNA-PK	0	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	-0.002	0.011	-10000	0	-10000	0	0
FANCF	0.013	0	-10000	0	-10000	0	0
BRCA1	0.013	0	-10000	0	-10000	0	0
CCNE1	0.013	0	-10000	0	-10000	0	0
CDK2/Cyclin E1	0	0	-10000	0	-10000	0	0
FANCG	0.013	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	-0.031	0.14	-10000	0	-0.66	19	19
FANCE	0.013	0	-10000	0	-10000	0	0
FANCC	0.013	0	-10000	0	-10000	0	0
NBN	0.013	0	-10000	0	-10000	0	0
FANCA	-0.004	0.072	-10000	0	-0.31	21	21
DNA repair	0.054	0.099	-10000	0	-10000	0	0
BRCA1/BARD1/ubiquitin	-0.031	0.14	-10000	0	-0.66	19	19
BARD1/DNA-PK	-0.024	0.11	-10000	0	-0.52	19	19
FANCL	0.013	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.03	0.14	0.66	19	-10000	0	19
BRCA1/BARD1/CTIP/M/R/N Complex	0.024	0.085	-10000	0	-0.34	20	20
BRCA1/BACH1/BARD1/TopBP1	-0.026	0.12	-10000	0	-0.57	19	19
BRCA1/BARD1/P53	-0.024	0.11	-10000	0	-0.52	19	19
BARD1/CSTF1/BRCA1	-0.026	0.12	-10000	0	-0.57	19	19
BRCA1/BACH1	0.013	0	-10000	0	-10000	0	0
BARD1	-0.027	0.18	-10000	0	-0.85	19	19
PCNA	0.013	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	-0.026	0.12	-10000	0	-0.57	19	19
BRCA1/BARD1/UbcH7	-0.026	0.12	-10000	0	-0.57	19	19
BRCA1/BARD1/RAD51/PCNA	-0.025	0.11	-10000	0	-0.52	19	19
BARD1/DNA-PK/P53	-0.023	0.1	-10000	0	-0.48	19	19
BRCA1/BARD1/Ubiquitin	-0.031	0.14	-10000	0	-0.66	19	19
BRCA1/BARD1/CTIP	-0.025	0.11	-10000	0	-0.52	20	20
FA complex	0.038	0.022	-10000	0	-10000	0	0
BARD1/EWS	-0.031	0.14	-10000	0	-0.66	19	19
RBBP8	0.023	0.034	-10000	0	-0.66	1	1
TP53	0.013	0	-10000	0	-10000	0	0
TOPBP1	0.013	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.024	0.11	0.52	19	-10000	0	19
BRCA1/BARD1	-0.024	0.1	-10000	0	-0.49	20	20
CSTF1	0.013	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.031	0.14	-10000	0	-0.67	19	19
CDK2	0.013	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.01	0.032	-10000	0	-0.31	4	4
RAD50	0.013	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.031	0.14	-10000	0	-0.66	19	19
EWSR1	0.013	0	-10000	0	-10000	0	0

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.013	0	-10000	0	-10000	0	0
mol:PIP3	-0.038	0.11	0.34	1	-0.36	44	45
FRAP1	0.009	0.024	-10000	0	-10000	0	0
AKT1	-0.031	0.094	0.25	1	-0.68	1	2
INSR	0.013	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0	0	-10000	0	-10000	0	0
mol:GTP	-0.024	0.07	-10000	0	-0.53	1	1
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.007	0.02	-10000	0	-10000	0	0
TSC2	0.013	0	-10000	0	-10000	0	0
RHEB/GDP	-0.02	0.059	-10000	0	-0.48	1	1
TSC1	0.013	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	-0.03	0.14	-10000	0	-0.43	43	43
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.008	0.024	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.013	0	-10000	0	-10000	0	0
RPS6KB1	0.012	0.055	-10000	0	-0.38	1	1
MAP3K5	0.011	0.023	-10000	0	-0.46	1	1
PIK3R1	0.013	0	-10000	0	-10000	0	0
apoptosis	0.01	0.023	-10000	0	-0.46	1	1
mol:LY294002	0	0.001	0.001	1	-0.002	43	44
EIF4B	0.02	0.05	-10000	0	-0.32	1	1
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.012	0.035	-10000	0	-0.3	1	1
eIF4E/eIF4G1/eIF4A1	-0.001	0.006	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	-0.019	0.13	-10000	0	-0.39	44	44
mTOR/RHEB/GTP/Raptor/GBL	0.023	0.037	0.18	1	-0.27	1	2
FKBP1A	0.013	0.001	-10000	0	-10000	0	0
RHEB/GTP	-0.02	0.058	-10000	0	-0.48	1	1
mol:Amino Acids	0	0.001	0.001	1	-0.002	43	44
FKBP12/Rapamycin	0	0.001	-10000	0	-10000	0	0
PDPK1	-0.035	0.11	0.26	1	-0.33	44	45
EIF4E	0.013	0	-10000	0	-10000	0	0
ASK1/PP5C	0.016	0.036	-10000	0	-0.63	1	1
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.018	0.001	-10000	0	-10000	0	0
TSC1/TSC2	-0.025	0.075	-10000	0	-0.59	1	1
tumor necrosis factor receptor activity	0	0.001	0.002	43	-0.001	1	44
RPS6	0.013	0	-10000	0	-10000	0	0
PPP5C	0.013	0	-10000	0	-10000	0	0
EIF4G1	0.013	0	-10000	0	-10000	0	0
IRS1	-0.041	0.15	-10000	0	-0.47	43	43
INS	0	0	-10000	0	-10000	0	0
PTEN	0.011	0.043	-10000	0	-0.85	1	1
PDK2	-0.034	0.1	0.26	1	-0.32	44	45
EIF4EBP1	0.012	0.01	-10000	0	-10000	0	0
PIK3CA	0.011	0.043	-10000	0	-0.85	1	1
PPP2R5D	0.016	0.022	-10000	0	-10000	0	0
peptide biosynthetic process	0.018	0	-10000	0	-10000	0	0
RHEB	0.013	0	-10000	0	-10000	0	0
EIF4A1	0.013	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	0.004	1	-0.004	1	2
EEF2	0.018	0	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.018	0.009	-10000	0	-10000	0	0

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.017	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.069	0.057	-9999	-10000	0	0
ERC1	0.013	0	-9999	-10000	0	0
RIP2/NOD2	-0.028	0.075	-9999	-0.66	1	1
NFKBIA	0.05	0	-9999	-10000	0	0
BIRC2	0.013	0	-9999	-10000	0	0
IKBKB	0.013	0	-9999	-10000	0	0
RIPK2	0.013	0	-9999	-10000	0	0
IKBKG	-0.005	0.017	-9999	-10000	0	0
IKK complex/A20	-0.05	0.13	-9999	-0.41	47	47
NEMO/A20/RIP2	0.013	0	-9999	-10000	0	0
XPO1	0.013	0	-9999	-10000	0	0
NEMO/ATM	0.042	0.038	-9999	-0.45	1	1
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.013	0	-9999	-10000	0	0
Exportin 1/RanGTP	0	0	-9999	-10000	0	0
IKK complex/ELKS	-0.001	0.011	-9999	-10000	0	0
BCL10/MALT1/TRAF6	-0.001	0.028	-9999	-0.57	1	1
NOD2	-0.032	0.12	-9999	-0.32	55	55
NFKB1	0.017	0	-9999	-10000	0	0
RELA	0.017	0	-9999	-10000	0	0
MALT1	0.013	0	-9999	-10000	0	0
cIAP1/UbcH5C	0	0	-9999	-10000	0	0
ATM	0.011	0.043	-9999	-0.85	1	1
TNF/TNFR1A	-0.078	0.21	-9999	-0.66	47	47
TRAF6	0.011	0.043	-9999	-0.85	1	1
PRKCA	-0.038	0.2	-9999	-0.85	24	24
CHUK	0.013	0	-9999	-10000	0	0
UBE2D3	0.013	0	-9999	-10000	0	0
TNF	-0.091	0.28	-9999	-0.79	53	53
NF kappa B1 p50/RelA	0	0	-9999	-10000	0	0
BCL10	0.013	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.05	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.017	0	-9999	-10000	0	0
TNFRSF1A	0.013	0	-9999	-10000	0	0
IKK complex	-0.002	0.013	-9999	-10000	0	0
CYLD	0.013	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.025	0.097	-9999	-0.41	24	24

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.024	0	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0	0	-10000	0	-10000	0	0
CDKN1B	0.039	0.009	-10000	0	-10000	0	0
CDKN1A	0.034	0.03	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.013	0	-10000	0	-10000	0	0
FOXO3	0.039	0.009	-10000	0	-10000	0	0
AKT1	0	0.008	-10000	0	-10000	0	0
BAD	0.013	0	-10000	0	-10000	0	0
AKT3	0.017	0.024	-10000	0	-0.46	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.039	0.009	-10000	0	-10000	0	0
AKT1/ASK1	-0.001	0.023	-10000	0	-0.45	1	1
BAD/YWHAZ	0	0	-10000	0	-10000	0	0
RICTOR	0.013	0	-10000	0	-10000	0	0
RAF1	0.013	0	-10000	0	-10000	0	0
JNK cascade	0.001	0.023	0.44	1	-10000	0	1
TSC1	0.039	0.009	-10000	0	-10000	0	0
YWHAZ	0.013	0	-10000	0	-10000	0	0
AKT1/RAF1	0.038	0.009	-10000	0	-10000	0	0
EP300	0.013	0	-10000	0	-10000	0	0
mol:GDP	0	0.008	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.039	0.009	-10000	0	-10000	0	0
YWHAQ	0.013	0	-10000	0	-10000	0	0
TBC1D4	-0.043	0.19	-10000	0	-0.57	47	47
MAP3K5	0.011	0.043	-10000	0	-0.85	1	1
MAPKAP1	0.013	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.01	0.036	-10000	0	-10000	0	0
YWHAH	0.013	0	-10000	0	-10000	0	0
AKT1S1	0.039	0.009	-10000	0	-10000	0	0
CASP9	0.039	0.009	-10000	0	-10000	0	0
YWHAB	0.013	0	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.045	0.009	-10000	0	-10000	0	0
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	-0.002	0.029	-10000	0	-0.57	1	1
YWHAE	0.013	0	-10000	0	-10000	0	0
SRC	0.012	0.016	-10000	0	-0.31	1	1
AKT2/p21CIP1	-0.005	0.025	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.019	0.003	-10000	0	-10000	0	0
CHUK	0.039	0.009	-10000	0	-10000	0	0
BAD/BCL-XL	0.052	0.009	-10000	0	-10000	0	0
mTORC2	0	0	-10000	0	-10000	0	0
AKT2	0.017	0.024	-10000	0	-0.46	1	1
FOXO1-3a-4/14-3-3 family	0.024	0.041	-10000	0	-10000	0	0
PDPK1	0.011	0.043	-10000	0	-0.85	1	1
MDM2	0.039	0.009	-10000	0	-10000	0	0
MAPKKK cascade	-0.038	0.009	-10000	0	-10000	0	0
MDM2/Cbp/p300	0	0.006	-10000	0	-10000	0	0
TSC1/TSC2	0.046	0.009	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0.006	-10000	0	-10000	0	0
glucose import	-0.052	0.21	-10000	0	-0.55	59	59
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.034	0.006	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.053	0.21	-10000	0	-0.56	59	59
GSK3A	0.039	0.009	-10000	0	-10000	0	0
FOXO1	0.039	0.009	-10000	0	-10000	0	0
GSK3B	0.039	0.009	-10000	0	-10000	0	0
SFN	-0.21	0.19	-10000	0	-0.34	265	265
G1/S transition of mitotic cell cycle	0.046	0.009	-10000	0	-10000	0	0
p27Kip1/14-3-3 family	-0.002	0.053	-10000	0	-10000	0	0
PRKACA	0.013	0	-10000	0	-10000	0	0
KPNA1	0.013	0	-10000	0	-10000	0	0
HSP90AA1	0.013	0	-10000	0	-10000	0	0
YWHAG	0.013	0	-10000	0	-10000	0	0
RHEB	0.013	0	-10000	0	-10000	0	0
CREBBP	0.013	0	-10000	0	-10000	0	0

×

TRAIL signaling pathway

Figure S98. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S98. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.008	0.062	-9999	-0.67	3	3
positive regulation of NF-kappaB transcription factor activity	-0.004	0.047	-9999	-0.66	2	2
MAP2K4	0.048	0.028	-9999	-10000	0	0
IKBKB	0.013	0	-9999	-10000	0	0
TNFRSF10B	0.013	0	-9999	-10000	0	0
TNFRSF10A	0.009	0.06	-9999	-0.85	2	2
SMPD1	-0.002	0.021	-9999	-0.3	2	2
IKBKG	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
TNFRSF10D	0.013	0	-9999	-10000	0	0
TRAIL/TRAILR2	-0.004	0.047	-9999	-0.66	2	2
TRAIL/TRAILR3	-0.064	0.1	-9999	-0.66	2	2
TRAIL/TRAILR1	-0.007	0.065	-9999	-0.66	4	4
TRAIL/TRAILR4	-0.004	0.047	-9999	-0.66	2	2
TRAIL/TRAILR1/DAP3/GTP	-0.005	0.052	-9999	-0.53	4	4
IKK complex	-0.002	0.016	-9999	-10000	0	0
RIPK1	0.013	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
DAP3/GTP	0	0	-9999	-10000	0	0
MAPK3	0.02	0.049	-9999	-0.66	2	2
MAP3K1	-0.002	0.025	-9999	-0.33	2	2
TRAILR4 (trimer)	0.013	0	-9999	-10000	0	0
TRADD	0.013	0	-9999	-10000	0	0
TRAILR1 (trimer)	0.009	0.06	-9999	-0.85	2	2
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.036	0.037	-9999	-0.34	4	4
CFLAR	0.013	0	-9999	-10000	0	0
MAPK1	0.02	0.049	-9999	-0.66	2	2
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.005	0.048	-9999	-0.48	4	4
mol:ceramide	-0.002	0.021	-9999	-0.3	2	2
FADD	0.013	0	-9999	-10000	0	0
MAPK8	0.051	0.05	-9999	-0.44	3	3
TRAF2	0.013	0	-9999	-10000	0	0
TRAILR3 (trimer)	-0.085	0.15	-9999	-0.31	123	123
CHUK	0.013	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD	-0.006	0.057	-9999	-0.57	4	4
DAP3	0.013	0	-9999	-10000	0	0
CASP10	-0.004	0.043	-9999	-0.54	2	2
JNK cascade	-0.004	0.047	-9999	-0.66	2	2
TRAIL (trimer)	0.008	0.062	-9999	-0.67	3	3
TNFRSF10C	-0.085	0.15	-9999	-0.31	123	123
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.005	0.049	-9999	-0.49	4	4
TRAIL/TRAILR2/FADD	-0.003	0.04	-9999	-0.57	2	2
cell death	-0.002	0.021	-9999	-0.3	2	2
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.037	0.027	-9999	-0.34	2	2
TRAILR2 (trimer)	0.013	0	-9999	-10000	0	0
CASP8	0.001	0.012	-9999	-10000	0	0
negative regulation of caspase activity	0	0	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.003	0.034	-9999	-0.48	2	2

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.004	0.13	-10000	0	-0.57	10	10
BAG4	0.011	0.043	-10000	0	-0.85	1	1
BAD	0.018	0.047	-10000	0	-10000	0	0
NFKBIA	0.013	0	-10000	0	-10000	0	0
BIRC3	-0.039	0.2	-10000	0	-0.69	30	30
BAX	0.018	0.047	-10000	0	-10000	0	0
EnzymeConsortium:3.1.4.12	0.004	0.034	-10000	0	-0.12	10	10
IKBKB	0.013	0.13	-10000	0	-0.53	10	10
MAP2K2	0.028	0.055	-10000	0	-0.38	1	1
MAP2K1	0.028	0.055	-10000	0	-0.38	1	1
SMPD1	0.01	0.034	-10000	0	-10000	0	0
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.013	0.13	-10000	0	-0.55	10	10
MAP2K4	0.024	0.047	-10000	0	-10000	0	0
protein ubiquitination	0.014	0.13	-10000	0	-0.54	10	10
EnzymeConsortium:2.7.1.37	0.032	0.061	-10000	0	-0.39	1	1
response to UV	0	0.001	-10000	0	-0.003	1	1
RAF1	0.023	0.055	-10000	0	-0.42	1	1
CRADD	0.013	0	-10000	0	-10000	0	0
mol:ceramide	0.01	0.049	-10000	0	-0.17	10	10
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-10000	0	-10000	0	0
MADD	0.013	0	-10000	0	-10000	0	0
MAP3K1	0.018	0.048	-10000	0	-10000	0	0
TRADD	0.013	0	-10000	0	-10000	0	0
RELA/p50	0.013	0	-10000	0	-10000	0	0
MAPK3	0.031	0.055	-10000	0	-0.37	1	1
MAPK1	0.031	0.055	-10000	0	-0.37	1	1
p50/RELA/I-kappa-B-alpha	0	0	-10000	0	-10000	0	0
FADD	0.004	0.13	-10000	0	-0.57	10	10
KSR1	0.016	0.054	-10000	0	-0.45	1	1
MAPK8	0.028	0.062	-10000	0	-0.47	3	3
TRAF2	0.013	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	0.013	0.13	-10000	0	-0.53	10	10
TNF R/SODD	-0.002	0.032	-10000	0	-0.66	1	1
TNF	-0.091	0.28	-10000	0	-0.79	53	53
CYCS	0.027	0.056	0.16	22	-10000	0	22
IKBKG	0.013	0.13	-10000	0	-0.53	10	10
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.004	0.14	-10000	0	-0.47	21	21
RELA	0.013	0	-10000	0	-10000	0	0
RIPK1	0.013	0	-10000	0	-10000	0	0
AIFM1	0.027	0.056	0.16	22	-10000	0	22
TNF/TNF R/SODD	-0.069	0.18	-10000	0	-0.57	48	48
TNFRSF1A	0.013	0	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.019	0.034	-10000	0	-10000	0	0
NSMAF	0.005	0.13	-10000	0	-0.56	10	10
response to hydrogen peroxide	0	0.001	-10000	0	-0.003	1	1
BCL2	-0.042	0.21	-10000	0	-0.85	26	26

×

S1P1 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.008	0.072	-9999	-0.66	5	5
PDGFRB	0.013	0.004	-9999	-10000	0	0
SPHK1	-0.008	0.022	-9999	-10000	0	0
mol:S1P	-0.009	0.026	-9999	-10000	0	0
S1P1/S1P/Gi	0.011	0.16	-9999	-0.61	13	13
GNAO1	-0.015	0.15	-9999	-0.72	16	16
PDGFB-D/PDGFRB/PLCgamma1	0.022	0.14	-9999	-0.6	9	9
PLCG1	0.018	0.15	-9999	-0.66	9	9
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.013	0.004	-9999	-10000	0	0
GNAI2	0.013	0.005	-9999	-10000	0	0
GNAI3	0.013	0.005	-9999	-10000	0	0
GNAI1	0.013	0.005	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.011	0.065	-9999	-0.57	5	5
S1P1/S1P	-0.017	0.059	-9999	-0.43	5	5
negative regulation of cAMP metabolic process	0.012	0.15	-9999	-0.58	13	13
MAPK3	0.003	0.21	-9999	-0.6	39	39
calcium-dependent phospholipase C activity	-0.001	0.003	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
KDR	0.006	0.074	-9999	-0.85	3	3
PLCB2	0.029	0.068	-9999	-0.38	5	5
RAC1	0.013	0	-9999	-10000	0	0
RhoA/GTP	-0.014	0.049	-9999	-0.36	5	5
receptor internalization	-0.016	0.055	-9999	-0.4	5	5
PTGS2	-0.044	0.36	-9999	-1.1	39	39
Rac1/GTP	-0.014	0.049	-9999	-0.36	5	5
RHOA	0.013	0	-9999	-10000	0	0
VEGFA	0.008	0.06	-9999	-0.85	2	2
negative regulation of T cell proliferation	0.012	0.15	-9999	-0.58	13	13
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.013	0.005	-9999	-10000	0	0
MAPK1	0.003	0.21	-9999	-0.6	39	39
S1P1/S1P/PDGFB-D/PDGFRB	0.032	0.079	-9999	-0.44	5	5
ABCC1	0.013	0.002	-9999	-10000	0	0

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.024	0.091	-9999	-10000	0	0
RAD9A	0.013	0	-9999	-10000	0	0
AP1	-0.3	0.47	-9999	-0.98	124	124
IFNAR2	0.014	0.003	-9999	-10000	0	0
AKT1	-0.001	0.071	-9999	-10000	0	0
ER alpha/Oestrogen	-0.045	0.15	-9999	-0.66	19	19
NFX1/SIN3/HDAC complex	0.048	0.018	-9999	-10000	0	0
EGF	-0.11	0.3	-9999	-0.8	61	61
SMG5	0.013	0	-9999	-10000	0	0
SMG6	0.013	0	-9999	-10000	0	0
SP3/HDAC2	0.005	0.01	-9999	-10000	0	0
TERT/c-Abl	-0.037	0.066	-9999	-10000	0	0
SAP18	0.013	0	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	-0.03	0.11	-9999	-0.32	1	1
WRN	0.013	0	-9999	-10000	0	0
SP1	0.015	0.003	-9999	-10000	0	0
SP3	0.013	0.002	-9999	-10000	0	0
TERF2IP	0.013	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.029	0.051	-9999	-10000	0	0
Mad/Max	0	0	-9999	-10000	0	0
TERT	-0.025	0.092	-9999	-10000	0	0
CCND1	-0.017	0.091	-9999	-10000	0	0
MAX	0.013	0.002	-9999	-10000	0	0
RBBP7	0.013	0	-9999	-10000	0	0
RBBP4	0.013	0	-9999	-10000	0	0
TERF2	0	0.005	-9999	-10000	0	0
PTGES3	0.013	0	-9999	-10000	0	0
SIN3A	0.013	0	-9999	-10000	0	0
Telomerase/911	0.035	0.02	-9999	-10000	0	0
CDKN1B	-0.043	0.2	-9999	-0.55	54	54
RAD1	0.013	0	-9999	-10000	0	0
XRCC5	0.013	0	-9999	-10000	0	0
XRCC6	0.013	0	-9999	-10000	0	0
SAP30	0.011	0.043	-9999	-0.85	1	1
TRF2/PARP2	0	0.004	-9999	-10000	0	0
UBE3A	0.013	0.002	-9999	-10000	0	0
JUN	-0.18	0.36	-9999	-0.85	93	93
E6	0	0.001	-9999	-10000	0	0
HPV-16 E6/E6AP	0.003	0.005	-9999	-10000	0	0
FOS	-0.21	0.38	-9999	-0.85	106	106
IFN-gamma/IRF1	-0.09	0.22	-9999	-0.64	55	55
PARP2	0.013	0	-9999	-10000	0	0
BLM	0.012	0.016	-9999	-0.31	1	1
Telomerase	0.014	0.071	-9999	-0.48	4	4
IRF1	0.017	0.016	-9999	-0.3	1	1
ESR1	-0.048	0.2	-9999	-0.85	19	19
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	-0.001	0.029	-9999	-0.58	1	1
ubiquitin-dependent protein catabolic process	0.053	0.017	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.054	0.018	-9999	-10000	0	0
HDAC1	0.013	0	-9999	-10000	0	0
HDAC2	0.014	0.003	-9999	-10000	0	0
ATM	-0.001	0.028	-9999	-0.58	1	1
SMAD3	0.02	0.027	-9999	-10000	0	0
ABL1	0.013	0	-9999	-10000	0	0
MXD1	0.013	0.002	-9999	-10000	0	0
MRE11A	0.013	0	-9999	-10000	0	0
HUS1	0.013	0	-9999	-10000	0	0
RPS6KB1	0.013	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.031	0.059	-9999	-10000	0	0
NR2F2	0.012	0.002	-9999	-10000	0	0
MAPK3	0.017	0.006	-9999	-10000	0	0
MAPK1	0.017	0.006	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.008	0.039	-9999	-0.31	6	6
NFKB1	0.013	0	-9999	-10000	0	0
HNRNPC	0.013	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	-0.001	0.028	-9999	-0.57	1	1
NBN	0.013	0	-9999	-10000	0	0
EGFR	0.003	0.095	-9999	-0.85	5	5
mol:Oestrogen	0	0.001	-9999	-10000	0	0
EGF/EGFR	-0.099	0.23	-9999	-0.66	60	60
MYC	-0.008	0.13	-9999	-0.85	10	10
IL2	0.006	0.007	-9999	-10000	0	0
KU	0	0	-9999	-10000	0	0
RAD50	0.013	0	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
TGFB1	0.008	0.039	-9999	-0.31	6	6
TRF2/BLM	0	0.01	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.032	0.065	-9999	-10000	0	0
SP1/HDAC2	0.007	0.012	-9999	-10000	0	0
PINX1	0.013	0	-9999	-10000	0	0
Telomerase/EST1A	-0.029	0.051	-9999	-10000	0	0
Smad3/Myc	0.006	0.096	-9999	-0.58	10	10
911 complex	0	0	-9999	-10000	0	0
IFNG	-0.1	0.29	-9999	-0.75	65	65
Telomerase/PinX1	-0.029	0.051	-9999	-10000	0	0
Telomerase/AKT1/mTOR/p70S6K	0.021	0.037	-9999	-10000	0	0
SIN3B	0.013	0	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
Telomerase/EST1B	-0.029	0.051	-9999	-10000	0	0
response to DNA damage stimulus	0.003	0.008	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0	0.005	-9999	-10000	0	0
TRF2/WRN	0	0.004	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.029	0.051	-9999	-10000	0	0
E2F1	-0.088	0.15	-9999	-0.32	3	3
ZNFX1	0.013	0	-9999	-10000	0	0
PIF1	0.002	0.089	-9999	-0.85	4	4
NCL	0.013	0	-9999	-10000	0	0
DKC1	0.013	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.013	0	-9999	-10000	0	0
mol:S1P	0.002	0	-9999	-10000	0	0
S1P1/S1P/Gi	0.027	0.054	-9999	-0.28	12	12
GNAO1	-0.013	0.15	-9999	-0.72	16	16
S1P/S1P3/G12/G13	0	0	-9999	-10000	0	0
AKT1	-0.003	0.018	-9999	-10000	0	0
AKT3	0.05	0.041	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.013	0	-9999	-10000	0	0
GNAI2	0.015	0	-9999	-10000	0	0
GNAI3	0.015	0	-9999	-10000	0	0
GNAI1	0.015	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.015	0	-9999	-10000	0	0
S1PR2	0.012	0.023	-9999	-0.31	2	2
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.037	0.064	-9999	-0.33	12	12
MAPK3	0.044	0.061	-9999	-10000	0	0
MAPK1	0.044	0.061	-9999	-10000	0	0
JAK2	0.047	0.061	-9999	-10000	0	0
CXCR4	0.043	0.062	-9999	-10000	0	0
FLT1	0.016	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.043	0.061	-9999	-10000	0	0
S1P/S1P3/Gi	0.037	0.064	-9999	-0.33	12	12
RAC1	0.013	0	-9999	-10000	0	0
RhoA/GTP	-0.009	0.049	-9999	-10000	0	0
VEGFA	0.012	0.06	-9999	-0.85	2	2
S1P/S1P2/Gi	0.032	0.065	-9999	-0.33	12	12
VEGFR1 homodimer/VEGFA homodimer	0.025	0.048	-9999	-0.66	2	2
RHOA	0.013	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.062	0.17	-9999	-0.36	95	95
GNAQ	0.013	0	-9999	-10000	0	0
GNAZ	0.015	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
GNA14	-0.18	0.36	-9999	-0.85	92	92
GNA15	-0.012	0.094	-9999	-0.33	30	30
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
GNA11	0.005	0.085	-9999	-0.85	4	4
Rac1/GTP	-0.009	0.049	-9999	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	-0.064	0.13	-10000	0	-10000	0	0
regulation of axonogenesis	-0.01	0.034	0.3	1	-10000	0	1
myoblast fusion	0.032	0.047	-10000	0	-10000	0	0
mol:GTP	-0.028	0.04	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.094	0.11	0.54	1	-10000	0	1
ARF1/GTP	-0.016	0.023	-10000	0	-10000	0	0
mol:GM1	-0.012	0.034	-10000	0	-10000	0	0
mol:Choline	0.011	0.029	-10000	0	-10000	0	0
lamellipodium assembly	-0.005	0.064	-10000	0	-10000	0	0
MAPK3	-0.02	0.066	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.095	0.11	-10000	0	-0.55	1	1
ARF1	0.013	0	-10000	0	-10000	0	0
ARF6/GDP	-0.032	0.047	-10000	0	-10000	0	0
ARF1/GDP	0.002	0.059	-10000	0	-10000	0	0
ARF6	-0.003	0.023	-10000	0	-10000	0	0
RAB11A	0.013	0	-10000	0	-10000	0	0
TIAM1	-0.17	0.17	-10000	0	-0.32	230	230
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	-0.02	0.066	-10000	0	-10000	0	0
actin filament bundle formation	0.026	0.038	-10000	0	-10000	0	0
KALRN	-0.008	0.051	-10000	0	-10000	0	0
RAB11FIP3/RAB11A	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.026	0.038	-10000	0	-10000	0	0
NME1	0.01	0.007	-10000	0	-10000	0	0
Rac1/GDP	-0.026	0.038	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	-0.028	0.04	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	-0.005	0.064	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
liver development	-0.028	0.04	-10000	0	-10000	0	0
ARF6/GTP	-0.028	0.04	-10000	0	-10000	0	0
RhoA/GTP	-0.016	0.023	-10000	0	-10000	0	0
mol:GDP	-0.014	0.065	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	-0.01	0.014	-10000	0	-10000	0	0
RHOA	0.013	0	-10000	0	-10000	0	0
PLD1	-0.001	0.034	-10000	0	-10000	0	0
RAB11FIP3	0.013	0	-10000	0	-10000	0	0
tube morphogenesis	-0.005	0.064	-10000	0	-10000	0	0
ruffle organization	0.01	0.034	-10000	0	-0.3	1	1
regulation of epithelial cell migration	-0.028	0.04	-10000	0	-10000	0	0
PLD2	-0.001	0.034	-10000	0	-10000	0	0
PIP5K1A	0.009	0.034	-10000	0	-0.3	1	1
mol:Phosphatidic acid	0.011	0.029	-10000	0	-10000	0	0
Rac1/GTP	-0.005	0.064	-10000	0	-10000	0	0

×

Canonical Wnt 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.006	0.022	-10000	0	-10000	0	0
AES	0.005	0.019	-10000	0	-10000	0	0
FBXW11	0.013	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0	0	-10000	0	-10000	0	0
SMAD4	0.013	0	-10000	0	-10000	0	0
DKK2	-0.031	0.18	-10000	0	-0.65	27	27
TLE1	0.001	0.061	-10000	0	-0.82	2	2
MACF1	0.013	0	-10000	0	-10000	0	0
CTNNB1	0.047	0.042	-10000	0	-10000	0	0
WIF1	-0.034	0.1	-10000	0	-0.31	50	50
beta catenin/RanBP3	0.021	0.09	0.37	20	-10000	0	20
KREMEN2	-0.011	0.085	-10000	0	-10000	0	0
DKK1	-0.041	0.13	-10000	0	-0.33	64	64
beta catenin/beta TrCP1	0.052	0.04	-10000	0	-10000	0	0
FZD1	0.014	0.001	-10000	0	-10000	0	0
AXIN2	-0.047	0.31	-10000	0	-1.6	15	15
AXIN1	0.014	0	-10000	0	-10000	0	0
RAN	0.013	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.006	0.019	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.063	0.041	-10000	0	-10000	0	0
Axin1/APC/GSK3	0.007	0.032	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin/Macf1	0.059	0.016	-10000	0	-10000	0	0
HNF1A	0.004	0.047	-10000	0	-0.86	1	1
CTBP1	0.006	0.02	-10000	0	-10000	0	0
MYC	-0.029	0.25	-10000	0	-1.6	10	10
RANBP3	0.013	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.039	0.12	-10000	0	-0.6	17	17
NKD1	-0.017	0.15	-10000	0	-0.75	16	16
TCF4	0.006	0.02	-10000	0	-10000	0	0
TCF3	0.006	0.02	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	-0.001	0.009	-10000	0	-10000	0	0
Ran/GTP	0.001	0.004	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.029	0.11	0.46	24	-10000	0	24
LEF1	0	0.046	-10000	0	-0.32	6	6
DVL1	0.014	0.027	-10000	0	-10000	0	0
CSNK2A1	0.013	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.068	0.067	-10000	0	-0.63	1	1
DKK1/LRP6/Kremen 2	-0.038	0.083	-10000	0	-0.65	2	2
LRP6	0.013	0	-10000	0	-10000	0	0
CSNK1A1	0.006	0.022	-10000	0	-10000	0	0
NLK	0.013	0.004	-10000	0	-10000	0	0
CCND1	0	0.071	-10000	0	-10000	0	0
WNT1	0.009	0.023	-10000	0	-0.31	2	2
GSK3A	0.014	0	-10000	0	-10000	0	0
GSK3B	0.013	0.001	-10000	0	-10000	0	0
FRAT1	0.013	0	-10000	0	-10000	0	0
PPP2R5D	0.031	0.064	0.37	13	-10000	0	13
APC	0.039	0.013	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.035	0.037	-10000	0	-10000	0	0
CREBBP	0.006	0.02	-10000	0	-10000	0	0

×

Effects of Botulinum toxin

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.012	0	-9999	-10000	0	0
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	0	0.01	-9999	-10000	0	0
STXBP1	0.013	0	-9999	-10000	0	0
ACh/CHRNA1	-0.016	0.065	-9999	-0.29	2	2
RAB3GAP2/RIMS1/UNC13B	0	0.008	-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	0.011	0.017	-9999	-0.31	1	1
mol:ACh	-0.007	0.041	-9999	-0.16	24	24
RAB3GAP2	0.013	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.014	0.044	-9999	-10000	0	0
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.016	0.065	-9999	-0.29	2	2
UNC13B	0.013	0	-9999	-10000	0	0
CHRNA1	-0.02	0.095	-9999	-0.31	39	39
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.12	0.17	-9999	-0.64	27	27
SNAP25	-0.032	0.098	-9999	-0.39	24	24
VAMP2	0.007	0	-9999	-10000	0	0
SYT1	-0.18	0.24	-9999	-0.85	27	27
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	0.019	0	-9999	-10000	0	0
STX1A/SNAP25 fragment 1/VAMP2	-0.014	0.044	-9999	-10000	0	0

×

FoxO family signaling

Figure S106. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S106. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.04	0.017	-9999	-10000	0	0
PLK1	0.11	0.096	-9999	-10000	0	0
CDKN1B	0.15	0.033	-9999	-10000	0	0
FOXO3	0.11	0.096	-9999	-10000	0	0
KAT2B	0.025	0.009	-9999	-10000	0	0
FOXO1/SIRT1	0.011	0.027	-9999	-10000	0	0
CAT	0.11	0.089	-9999	-10000	0	0
CTNNB1	0.013	0	-9999	-10000	0	0
AKT1	0.028	0.01	-9999	-10000	0	0
FOXO1	0.043	0.012	-9999	-10000	0	0
MAPK10	0.044	0.006	-9999	-10000	0	0
mol:GTP	0.002	0.001	-9999	-10000	0	0
FOXO4	0.11	0.039	-9999	-0.47	1	1
response to oxidative stress	0.015	0.012	-9999	-10000	0	0
FOXO3A/SIRT1	0.015	0.059	-9999	-10000	0	0
XPO1	0.014	0	-9999	-10000	0	0
EP300	0.015	0.001	-9999	-10000	0	0
BCL2L11	0.041	0.027	-9999	-10000	0	0
FOXO1/SKP2	0.042	0.028	-9999	-0.49	1	1
mol:GDP	0.015	0.012	-9999	-10000	0	0
RAN	0.015	0.001	-9999	-10000	0	0
GADD45A	0.13	0.035	-9999	-10000	0	0
YWHAQ	0.013	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.04	0.042	-9999	-10000	0	0
MST1	0.022	0.046	-9999	-0.57	2	2
CSNK1D	0.013	0	-9999	-10000	0	0
CSNK1E	0.013	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.008	0.066	-9999	-10000	0	0
YWHAB	0.013	0	-9999	-10000	0	0
MAPK8	0.041	0.047	-9999	-0.51	3	3
MAPK9	0.044	0.006	-9999	-10000	0	0
YWHAG	0.013	0	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
YWHAZ	0.013	0	-9999	-10000	0	0
SIRT1	0.008	0.021	-9999	-10000	0	0
SOD2	0.16	0.047	-9999	-10000	0	0
RBL2	0.12	0.098	-9999	-1.2	1	1
RAL/GDP	0.033	0.012	-9999	-10000	0	0
CHUK	0.025	0.009	-9999	-10000	0	0
Ran/GTP	0.015	0.001	-9999	-10000	0	0
CSNK1G2	0.013	0	-9999	-10000	0	0
RAL/GTP	0.042	0.009	-9999	-10000	0	0
CSNK1G1	0.013	0	-9999	-10000	0	0
FASLG	-0.079	0.42	-9999	-1.5	31	31
SKP2	0.011	0.043	-9999	-0.85	1	1
USP7	0.015	0.001	-9999	-10000	0	0
IKBKB	0.025	0.009	-9999	-10000	0	0
CCNB1	0.11	0.089	-9999	-10000	0	0
FOXO1-3a-4/beta catenin	-0.003	0.036	-9999	-0.41	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.042	0.028	-9999	-0.48	1	1
CSNK1A1	0.013	0	-9999	-10000	0	0
SGK1	0.01	0.11	-9999	-0.84	7	7
CSNK1G3	0.013	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.026	0.002	-9999	-10000	0	0
ZFAND5	0.11	0.034	-9999	-10000	0	0
SFN	-0.21	0.19	-9999	-0.34	265	265
CDK2	0.014	0.002	-9999	-10000	0	0
FOXO3A/14-3-3	0.016	0.063	-9999	-10000	0	0
CREBBP	0.014	0.002	-9999	-10000	0	0
FBXO32	0.11	0.091	-9999	-10000	0	0
BCL6	0.12	0.097	-9999	-1.2	1	1
RALB	0.015	0	-9999	-10000	0	0
RALA	0.015	0	-9999	-10000	0	0
YWHAH	0.013	0	-9999	-10000	0	0

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.044	0.007	-9999	-10000	0	0
KLHL20	-0.01	0.023	-9999	-10000	0	0
CYFIP2	0.013	0	-9999	-10000	0	0
Rac1/GDP	0.074	0.009	-9999	-10000	0	0
ENAH	0.044	0.007	-9999	-10000	0	0
AP1M1	0.013	0	-9999	-10000	0	0
RAP1B	0.013	0	-9999	-10000	0	0
RAP1A	0.013	0	-9999	-10000	0	0
CTNNB1	0.013	0	-9999	-10000	0	0
CDC42/GTP	0	0.002	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.002	0.016	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.019	0.087	-9999	-0.52	11	11
RAPGEF1	0.058	0.007	-9999	-10000	0	0
CTNND1	0.013	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0	0	-9999	-10000	0	0
CRK	0.052	0.007	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin	0	0	-9999	-10000	0	0
alphaE/beta7 Integrin	-0.026	0.11	-9999	-0.66	11	11
IQGAP1	0.013	0	-9999	-10000	0	0
NCKAP1	0.013	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0	0	-9999	-10000	0	0
DLG1	0.044	0.007	-9999	-10000	0	0
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.011	-9999	-10000	0	0
MLLT4	0.013	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.079	0.073	-9999	-0.53	1	1
PI3K	-0.001	0.014	-9999	-10000	0	0
ARF6	0.013	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	0	0	-9999	-10000	0	0
TIAM1	-0.17	0.16	-9999	-0.32	230	230
E-cadherin(dimer)/Ca2+	0	0	-9999	-10000	0	0
AKT1	0	0.008	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
CDH1	0.013	0	-9999	-10000	0	0
RhoA/GDP	0.073	0.009	-9999	-10000	0	0
actin cytoskeleton organization	-0.007	0.017	-9999	-10000	0	0
CDC42/GDP	0.073	0.009	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.026	0	-9999	-10000	0	0
ITGB7	-0.024	0.15	-9999	-0.52	28	28
RAC1	0.013	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin	0	0	-9999	-10000	0	0
mol:GDP	0.072	0.01	-9999	-10000	0	0
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	0.013	0	-9999	-10000	0	0
p120 catenin/RhoA/GDP	0	0.002	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0	0	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
CDC42	0.013	0	-9999	-10000	0	0
CTNNA1	0.013	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.013	0.034	-9999	-0.15	11	11
NME1	0.013	0	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.044	0.007	-9999	-10000	0	0
regulation of cell-cell adhesion	0	0.002	-9999	-10000	0	0
WASF2	0.002	0.009	-9999	-10000	0	0
Rap1/GTP	0	0.003	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.018	0.081	-9999	-0.48	11	11
CCND1	0.014	0.041	-9999	-0.18	11	11
VAV2	0.056	0.007	-9999	-10000	0	0
RAP1/GDP	0	0.002	-9999	-10000	0	0
adherens junction assembly	0.045	0.001	-9999	-10000	0	0
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.013	0	-9999	-10000	0	0
PIP5K1C	0.013	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.017	0.076	-9999	-0.46	11	11
E-cadherin/beta catenin	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SRC	0.044	0.01	-9999	-10000	0	0
PIK3CA	0.011	0.043	-9999	-0.85	1	1
Rac1/GTP	-0.018	0.036	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin	0	0	-9999	-10000	0	0
ITGAE	0.013	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0	0	-9999	-10000	0	0

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.015	0.15	-9999	-0.72	16	16
CDC42/GTP	-0.01	0.051	-9999	-0.3	12	12
PLCG1	0.032	0.061	-9999	-0.31	12	12
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.013	0	-9999	-10000	0	0
GNAI3	0.013	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
cell migration	-0.01	0.05	-9999	-0.3	12	12
S1PR5	0.009	0.036	-9999	-0.31	5	5
S1PR4	0.01	0.032	-9999	-0.31	4	4
MAPK3	0.032	0.061	-9999	-0.31	12	12
MAPK1	0.032	0.061	-9999	-0.31	12	12
S1P/S1P5/Gi	0.024	0.065	-9999	-0.34	12	12
GNAI1	0.013	0	-9999	-10000	0	0
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.002	0.018	-9999	-10000	0	0
RHOA	0.032	0.015	-9999	-10000	0	0
S1P/S1P4/Gi	0.024	0.065	-9999	-0.34	12	12
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	0.013	0	-9999	-10000	0	0
S1P/S1P4/G12/G13	-0.001	0.014	-9999	-10000	0	0
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
CDC42	0.013	0	-9999	-10000	0	0

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	-0.023	0.037	-9999	-10000	0	0
CLOCK	-0.017	0.15	-9999	-0.86	13	13
TIMELESS/CRY2	-0.002	0.062	-9999	-10000	0	0
DEC1/BMAL1	-0.024	0.067	-9999	-10000	0	0
ATR	0.013	0	-9999	-10000	0	0
NR1D1	-0.053	0.13	-9999	-10000	0	0
ARNTL	-0.024	0.1	-9999	-0.32	44	44
TIMELESS	-0.009	0.071	-9999	-10000	0	0
NPAS2	0.007	0.049	-9999	-0.49	3	3
CRY2	0.013	0	-9999	-10000	0	0
mol:CO	0.007	0.03	-9999	-10000	0	0
CHEK1	0.013	0	-9999	-10000	0	0
mol:HEME	-0.007	0.03	-9999	-10000	0	0
PER1	0.013	0	-9999	-10000	0	0
BMAL/CLOCK/NPAS2	-0.017	0.13	-9999	-0.6	14	14
BMAL1/CLOCK	-0.041	0.13	-9999	-0.63	7	7
S phase of mitotic cell cycle	-0.023	0.037	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	-0.023	0.037	-9999	-10000	0	0
mol:NADPH	-0.007	0.03	-9999	-10000	0	0
PER1/TIMELESS	-0.002	0.062	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	0	0.016	-9999	-0.31	1	1

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	0.012	0.082	-9999	-0.43	11	11
CRKL	0.013	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0.009	0.06	-9999	-0.85	2	2
ITGA4	0.007	0.045	-9999	-0.31	8	8
alpha4/beta7 Integrin/MAdCAM1	-0.031	0.097	-9999	-0.52	12	12
EPO	0.005	0.023	-9999	-0.31	2	2
alpha4/beta7 Integrin	-0.03	0.12	-9999	-0.64	12	12
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.004	0.028	-9999	-10000	0	0
EPO/EPOR (dimer)	-0.004	0.028	-9999	-10000	0	0
lamellipodium assembly	0	0.027	-9999	-0.52	1	1
PIK3CA	0.011	0.043	-9999	-0.85	1	1
PI3K	-0.002	0.032	-9999	-0.66	1	1
ARF6	0.013	0	-9999	-10000	0	0
JAK2	-0.003	0.015	-9999	-10000	0	0
PXN	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
MADCAM1	-0.01	0.086	-9999	-0.34	24	24
cell adhesion	-0.031	0.097	-9999	-0.52	12	12
CRKL/CBL	0	0	-9999	-10000	0	0
ITGB1	0.013	0	-9999	-10000	0	0
SRC	0.026	0.058	-9999	-0.52	3	3
ITGB7	-0.024	0.15	-9999	-0.52	28	28
RAC1	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.01	0.058	-9999	-0.57	3	3
p130Cas/Crk/Dock1	-0.009	0.052	-9999	-10000	0	0
VCAM1	0.002	0.083	-9999	-0.49	9	9
RHOA	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.003	0.018	-9999	-10000	0	0
BCAR1	0.034	0.055	-9999	-0.48	3	3
EPOR	0.008	0.039	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.013	0	-9999	-10000	0	0
GIT1	0.013	0	-9999	-10000	0	0
Rac1/GTP	0	0.027	-9999	-0.54	1	1

×

S1P5 pathway

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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.01	0.05	0.3	12	-10000	0	12
GNAI2	0.013	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.002	0.018	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.015	0.15	-10000	0	-0.72	16	16
RhoA/GTP	-0.01	0.051	-10000	0	-10000	0	0
negative regulation of cAMP metabolic process	0.024	0.064	-10000	0	-0.34	12	12
GNAZ	0.013	0	-10000	0	-10000	0	0
GNAI3	0.013	0	-10000	0	-10000	0	0
GNA12	0.013	0	-10000	0	-10000	0	0
S1PR5	0.009	0.036	-10000	0	-0.31	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	0.024	0.065	-10000	0	-0.34	12	12
RhoA/GDP	0	0	-10000	0	-10000	0	0
RHOA	0.013	0	-10000	0	-10000	0	0
GNAI1	0.013	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	-0.062	0.17	-9999	-0.52	47	47
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.05	0.14	-9999	-0.43	47	47
SUMO1	0.013	0	-9999	-10000	0	0
ZFPM1	0.013	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.023	0	-9999	-10000	0	0
FKBP3	0.013	0	-9999	-10000	0	0
Histones	-0.025	0.068	-9999	-10000	0	0
YY1/LSF	0.028	0.05	-9999	-0.55	3	3
SMG5	0.013	0	-9999	-10000	0	0
RAN	0.013	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	-0.044	0.12	-9999	-0.38	47	47
I kappa B alpha/HDAC1	-0.029	0.082	-9999	-10000	0	0
SAP18	0.013	0	-9999	-10000	0	0
RELA	-0.003	0.12	-9999	-0.33	47	47
HDAC1/Smad7	0	0	-9999	-10000	0	0
RANGAP1	0.013	0	-9999	-10000	0	0
HDAC3/TR2	-0.029	0.082	-9999	-10000	0	0
NuRD/MBD3 Complex	0.051	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.003	0.11	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	0.012	0.016	-9999	-0.31	1	1
GATA1	0.009	0.006	-9999	-10000	0	0
Mad/Max	0	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.061	0.002	-9999	-10000	0	0
RBBP7	0.013	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
RBBP4	0.013	0	-9999	-10000	0	0
MAX	0.013	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.013	0	-9999	-10000	0	0
NFKBIA	-0.008	0.1	-9999	-10000	0	0
KAT2B	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.046	0.015	-9999	-10000	0	0
SIN3 complex	-0.001	0.026	-9999	-0.52	1	1
SMURF1	0.013	0	-9999	-10000	0	0
CHD3	0.013	0	-9999	-10000	0	0
SAP30	0.011	0.043	-9999	-0.85	1	1
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.013	0	-9999	-10000	0	0
YY1/HDAC3	-0.024	0.072	-9999	-10000	0	0
YY1/HDAC2	0.033	0	-9999	-10000	0	0
YY1/HDAC1	0.033	0	-9999	-10000	0	0
NuRD/MBD2 Complex (MeCP1)	0.051	0	-9999	-10000	0	0
PPARG	-0.06	0.16	-9999	-0.47	51	51
HDAC8/hEST1B	0	0	-9999	-10000	0	0
UBE2I	0.013	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.013	0	-9999	-10000	0	0
TNFRSF1A	0.013	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	-0.029	0.082	-9999	-10000	0	0
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
CREBBP	0.013	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.054	0	-9999	-10000	0	0
HDAC1	0.013	0	-9999	-10000	0	0
HDAC3	-0.008	0.1	-9999	-10000	0	0
HDAC2	0.013	0	-9999	-10000	0	0
YY1	0.032	0	-9999	-10000	0	0
HDAC8	0.013	0	-9999	-10000	0	0
SMAD7	0.013	0	-9999	-10000	0	0
NCOR2	0.013	0	-9999	-10000	0	0
MXD1	0.013	0	-9999	-10000	0	0
STAT3	0.027	0	-9999	-10000	0	0
NFKB1	0.013	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.013	0	-9999	-10000	0	0
YY1/LSF/HDAC1	-0.004	0.043	-9999	-0.51	3	3
YY1/SAP30/HDAC1	-0.001	0.025	-9999	-0.51	1	1
EP300	0.013	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.027	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.008	0.1	-9999	-10000	0	0
histone deacetylation	0.051	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	-0.025	0.073	-9999	-10000	0	0
nuclear export	0	0	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
GATAD2B	0.013	0	-9999	-10000	0	0
GATAD2A	0.013	0	-9999	-10000	0	0
GATA2/HDAC3	-0.029	0.082	-9999	-10000	0	0
GATA1/HDAC1	0	0	-9999	-10000	0	0
GATA1/HDAC3	-0.03	0.083	-9999	-10000	0	0
CHD4	0.013	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.078	0.21	-9999	-0.66	47	47
SIN3/HDAC complex/Mad/Max	0.05	0.013	-9999	-10000	0	0
NuRD Complex	0.059	0	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.025	0.067	-9999	-10000	0	0
SIN3B	0.013	0	-9999	-10000	0	0
MTA2	0.013	0	-9999	-10000	0	0
SIN3A	0.013	0	-9999	-10000	0	0
XPO1	0.013	0	-9999	-10000	0	0
SUMO1/HDAC1	0	0	-9999	-10000	0	0
HDAC complex	0	0	-9999	-10000	0	0
GATA1/Fog1	0	0	-9999	-10000	0	0
FKBP25/HDAC1/HDAC2	0	0	-9999	-10000	0	0
TNF	-0.091	0.28	-9999	-0.79	53	53
negative regulation of cell growth	0.05	0.013	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.051	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.053	0.14	-9999	-0.45	47	47
SIN3/HDAC complex/NCoR1	0.048	0.013	-9999	-10000	0	0
TFCP2	0.007	0.074	-9999	-0.85	3	3
NR2C1	0.013	0	-9999	-10000	0	0
MBD3	0.013	0	-9999	-10000	0	0
MBD2	0.013	0	-9999	-10000	0	0

×

Atypical NF-kappaB 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
BCL3/RelA	0	0.01	-9999	-10000	0	0
FBXW11	0.013	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	-0.001	0.13	-9999	-0.57	20	20
NF kappa B1 p50/RelA/I kappa B alpha	0.045	0.033	-9999	-10000	0	0
NFKBIA	0.025	0.038	-9999	-0.28	5	5
MAPK14	0.013	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.028	0	-9999	-10000	0	0
ARRB2	0.018	0	-9999	-10000	0	0
REL	-0.029	0.19	-9999	-0.85	20	20
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.027	0.009	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.028	0	-9999	-10000	0	0
PIK3CA	0.011	0.043	-9999	-0.85	1	1
NF kappa B1 p50 dimer	0.021	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
NFKB1	0.024	0	-9999	-10000	0	0
RELA	0.013	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.032	0.037	-9999	-0.28	5	5
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.048	0.032	-9999	-10000	0	0
SRC	0.012	0.016	-9999	-0.31	1	1
PI3K	-0.002	0.032	-9999	-0.66	1	1
NF kappa B1 p50/RelA	0.032	0.037	-9999	-0.28	5	5
IKBKB	0.013	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.013	0	-9999	-10000	0	0
SYK	0.013	0	-9999	-10000	0	0
I kappa B alpha/PIK3R1	0.03	0.035	-9999	-10000	0	0
cell death	-0.003	0.023	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	-0.001	0.13	-9999	-0.57	20	20
LCK	-0.009	0.11	-9999	-0.45	20	20
BCL3	0.012	0.016	-9999	-0.31	1	1

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	-0.022	0.12	-9999	-0.7	13	13
AKT1	0.085	0.081	-9999	-0.61	4	4
PTK2B	0.037	0.13	-9999	-0.92	4	4
VEGFR2 homodimer/Frs2	-0.007	0.081	-9999	-0.94	3	3
CAV1	-0.01	0.14	-9999	-0.85	11	11
CALM1	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.009	0.083	-9999	-0.73	5	5
endothelial cell proliferation	0.073	0.1	-9999	-0.57	4	4
mol:Ca2+	0.051	0.084	-9999	-0.79	3	3
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.008	0.078	-9999	-0.69	5	5
RP11-342D11.1	0.042	0.084	-9999	-0.63	6	6
CDH5	0.013	0	-9999	-10000	0	0
VEGFA homodimer	-0.005	0.051	-9999	-0.52	4	4
SHC1	0.013	0	-9999	-10000	0	0
SHC2	0.007	0.074	-9999	-0.85	3	3
HRAS/GDP	-0.008	0.068	-9999	-0.63	4	4
SH2D2A	-0.037	0.19	-9999	-0.67	30	30
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.007	0.061	-9999	-0.62	3	3
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.036	0.14	-9999	-0.55	25	25
VEGFR1 homodimer	0.013	0	-9999	-10000	0	0
SHC/GRB2/SOS1	-0.009	0.073	-9999	-0.76	3	3
GRB10	0.052	0.084	-9999	-0.79	3	3
PTPN11	0.013	0	-9999	-10000	0	0
GRB2	0.013	0	-9999	-10000	0	0
PAK1	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.008	0.075	-9999	-0.8	3	3
HRAS	0.012	0.023	-9999	-0.31	2	2
VEGF/Rho/ROCK1/Integrin Complex	0.04	0.077	-9999	-0.5	4	4
HIF1A	0.013	0	-9999	-10000	0	0
FRS2	0.013	0	-9999	-10000	0	0
oxygen and reactive oxygen species metabolic process	-0.008	0.077	-9999	-0.68	5	5
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.005	0.085	-9999	-0.85	4	4
Nck/Pak	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.009	0.083	-9999	-0.73	5	5
mol:GDP	-0.008	0.071	-9999	-0.73	3	3
mol:NADP	0.077	0.062	-9999	-0.51	3	3
eNOS/Hsp90	0.079	0.058	-9999	-0.48	3	3
PIK3R1	0.013	0	-9999	-10000	0	0
mol:IP3	0.052	0.086	-9999	-0.8	3	3
HIF1A/ARNT	0	0	-9999	-10000	0	0
SHB	0.013	0	-9999	-10000	0	0
VEGFA	0.011	0.06	-9999	-0.85	2	2
VEGFC	0.011	0.043	-9999	-0.85	1	1
FAK1/Vinculin	0.059	0.11	-9999	-0.79	4	4
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.025	0.13	-9999	-0.98	4	4
PTPN6	0.013	0	-9999	-10000	0	0
EPAS1	0.021	0.035	-9999	-0.39	3	3
mol:L-citrulline	0.077	0.062	-9999	-0.51	3	3
ITGAV	0.011	0.043	-9999	-0.85	1	1
PIK3CA	0.011	0.043	-9999	-0.85	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.008	0.078	-9999	-0.84	3	3
VEGFR2 homodimer/VEGFA homodimer	-0.01	0.086	-9999	-0.69	6	6
VEGFR2/3 heterodimer	-0.012	0.11	-9999	-0.83	6	6
VEGFB	0.013	0	-9999	-10000	0	0
MAPK11	0.054	0.089	-9999	-0.65	6	6
VEGFR2 homodimer	0.031	0.093	-9999	-1	3	3
FLT1	0.013	0	-9999	-10000	0	0
NEDD4	0.014	0.043	-9999	-0.85	1	1
MAPK3	0.042	0.094	-9999	-0.69	4	4
MAPK1	0.042	0.094	-9999	-0.69	4	4
VEGFA145/NRP2	-0.019	0.07	-9999	-0.65	2	2
VEGFR1/2 heterodimer	-0.007	0.081	-9999	-0.94	3	3
KDR	0.031	0.093	-9999	-1.1	3	3
VEGFA165/NRP1/VEGFR2 homodimer	-0.016	0.084	-9999	-0.85	3	3
SRC	0.012	0.016	-9999	-0.31	1	1
platelet activating factor biosynthetic process	0.045	0.094	-9999	-0.78	3	3
PI3K	-0.01	0.078	-9999	-0.76	3	3
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.009	0.083	-9999	-0.73	5	5
FES	0.052	0.087	-9999	-0.64	6	6
GAB1	-0.009	0.076	-9999	-0.67	5	5
VEGFR2 homodimer/VEGFA homodimer/Src	-0.009	0.083	-9999	-0.73	5	5
CTNNB1	0.013	0	-9999	-10000	0	0
SOS1	0.013	0	-9999	-10000	0	0
ARNT	0.013	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.068	0.093	-9999	-0.57	3	3
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.009	0.083	-9999	-0.73	5	5
PI3K/GAB1	0.086	0.079	-9999	-0.64	3	3
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.008	0.075	-9999	-0.8	3	3
PRKACA	0.013	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.013	0.1	-9999	-0.74	7	7
HSP90AA1	0.013	0	-9999	-10000	0	0
CDC42	0.052	0.087	-9999	-0.82	3	3
actin cytoskeleton reorganization	-0.036	0.13	-9999	-0.55	25	25
PTK2	0.053	0.12	-9999	-0.75	6	6
EDG1	0.042	0.084	-9999	-0.63	6	6
mol:DAG	0.052	0.086	-9999	-0.8	3	3
CaM/Ca2+	-0.008	0.072	-9999	-0.74	3	3
MAP2K3	0.054	0.097	-9999	-0.77	3	3
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.01	0.081	-9999	-0.83	3	3
PLCG1	0.052	0.087	-9999	-0.82	3	3
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.009	0.079	-9999	-0.84	3	3
IQGAP1	0.013	0	-9999	-10000	0	0
YES1	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.009	0.083	-9999	-0.73	5	5
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.009	0.083	-9999	-0.73	5	5
cell migration	0.083	0.095	-9999	-0.69	3	3
mol:PI-3-4-5-P3	-0.009	0.071	-9999	-0.69	3	3
FYN	0.013	0	-9999	-10000	0	0
VEGFB/NRP1	-0.009	0.073	-9999	-0.75	3	3
mol:NO	0.077	0.062	-9999	-0.51	3	3
PXN	0.013	0	-9999	-10000	0	0
HRAS/GTP	-0.008	0.068	-9999	-0.63	4	4
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.05	0.088	-9999	-0.83	3	3
VHL	0.009	0.06	-9999	-0.85	2	2
ITGB3	-0.014	0.15	-9999	-0.85	13	13
NOS3	0.079	0.069	-9999	-0.58	3	3
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.013	0.093	-9999	-0.64	8	8
RAC1	0.013	0	-9999	-10000	0	0
PRKCA	0.029	0.15	-9999	-0.89	3	3
PRKCB	0.041	0.097	-9999	-0.74	3	3
VCL	0.013	0	-9999	-10000	0	0
VEGFA165/NRP1	0.042	0.085	-9999	-0.63	6	6
VEGFR1/2 heterodimer/VEGFA homodimer	-0.009	0.083	-9999	-0.73	5	5
VEGFA165/NRP2	-0.019	0.07	-9999	-0.65	2	2
MAPKKK cascade	-0.008	0.067	-9999	-0.67	3	3
NRP2	-0.013	0.089	-9999	-0.31	33	33
VEGFC homodimer	0.011	0.043	-9999	-0.85	1	1
NCK1	0.013	0	-9999	-10000	0	0
ROCK1	0.013	0	-9999	-10000	0	0
FAK1/Paxillin	0.059	0.11	-9999	-0.79	4	4
MAP3K13	0.047	0.1	-9999	-0.82	3	3
PDPK1	0.077	0.081	-9999	-0.63	4	4

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.008	0.039	-9999	-0.31	6	6
PLK4	0.013	0	-9999	-10000	0	0
regulation of centriole replication	0.021	0.027	-9999	-10000	0	0

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.006	0.012	-9999	-10000	0	0
BIRC5	-0.017	0.1	-9999	-0.33	36	36
NFKBIA	0.032	0.003	-9999	-10000	0	0
CPEB1	-0.052	0.23	-9999	-0.85	31	31
AKT1	0.032	0.003	-9999	-10000	0	0
NDEL1	0.013	0	-9999	-10000	0	0
Aurora A/BRCA1	0.003	0.009	-9999	-10000	0	0
NDEL1/TACC3	0.003	0.012	-9999	-10000	0	0
GADD45A	0.013	0	-9999	-10000	0	0
GSK3B	0.012	0.002	-9999	-10000	0	0
PAK1/Aurora A	0.006	0.012	-9999	-10000	0	0
MDM2	0.013	0	-9999	-10000	0	0
JUB	0.011	0.043	-9999	-0.85	1	1
TPX2	0.001	0.069	-9999	-10000	0	0
TP53	0.007	0.013	-9999	-10000	0	0
DLG7	0.021	0.003	-9999	-10000	0	0
AURKAIP1	0.012	0.016	-9999	-0.31	1	1
ARHGEF7	0.013	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	0.003	0.013	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.003	0.009	-9999	-10000	0	0
AURKA	0.025	0.004	-9999	-10000	0	0
AURKB	-0.013	0.025	-9999	-10000	0	0
CDC25B	0.006	0.017	-9999	-10000	0	0
G2/M transition checkpoint	0.001	0.027	-9999	-0.52	1	1
mRNA polyadenylation	-0.037	0.14	-9999	-0.52	31	31
Aurora A/CPEB	-0.038	0.14	-9999	-0.53	31	31
Aurora A/TACC1/TRAP/chTOG	0.004	0.013	-9999	-10000	0	0
BRCA1	0.013	0	-9999	-10000	0	0
centrosome duplication	0.006	0.012	-9999	-10000	0	0
regulation of centrosome cycle	0.002	0.011	-9999	-10000	0	0
spindle assembly	0	0	-9999	-10000	0	0
TDRD7	0.013	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.01	0.037	-9999	-0.47	1	1
CENPA	-0.008	0.017	-9999	-10000	0	0
Aurora A/PP2A	0.006	0.012	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.038	0.004	-9999	-10000	0	0
negative regulation of DNA binding	0.031	0.002	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0	0	-9999	-10000	0	0
RASA1	0.013	0	-9999	-10000	0	0
Ajuba/Aurora A	0.001	0.028	-9999	-0.53	1	1
mitotic prometaphase	0.006	0.01	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.025	0.004	-9999	-10000	0	0
TACC1	0.013	0	-9999	-10000	0	0
TACC3	0.012	0.016	-9999	-0.31	1	1
Aurora A/Antizyme1	0.003	0.013	-9999	-10000	0	0
Aurora A/RasGAP	0.006	0.012	-9999	-10000	0	0
OAZ1	0.013	0	-9999	-10000	0	0
RAN	0.013	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.012	0.002	-9999	-10000	0	0
GIT1	0.013	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0	0	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	0.001	0.069	-9999	-10000	0	0
PPP2R5D	0.013	0	-9999	-10000	0	0
Aurora A/TPX2	0.018	0.05	-9999	-10000	0	0
PAK1	0.013	0	-9999	-10000	0	0
CKAP5	0.013	0	-9999	-10000	0	0

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.057	0.096	-9999	-10000	0	0
CRKL	0.042	0.033	-9999	-10000	0	0
mol:DAG	0.045	0.042	-9999	-10000	0	0
HRAS	0.065	0.032	-9999	-10000	0	0
MAPK8	0.029	0.057	-9999	-0.58	3	3
RAP1A	0.042	0.033	-9999	-10000	0	0
GAB1	0.042	0.033	-9999	-10000	0	0
MAPK14	0.033	0.023	-9999	-10000	0	0
EPO	0.008	0.023	-9999	-10000	0	0
PLCG1	0.045	0.042	-9999	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0.011	0.039	-9999	-10000	0	0
RAPGEF1	0.013	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.049	0.16	-9999	-0.6	32	32
GAB1/SHC/GRB2/SOS1	-0.003	0.012	-9999	-10000	0	0
EPO/EPOR (dimer)	0.016	0.031	-9999	-10000	0	0
IRS2	0.042	0.033	-9999	-10000	0	0
STAT1	0.047	0.069	-9999	-10000	0	0
STAT5B	0.047	0.057	-9999	-10000	0	0
cell proliferation	0.036	0.054	-9999	-0.54	3	3
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.006	0.017	-9999	-10000	0	0
TEC	0.042	0.033	-9999	-10000	0	0
SOCS3	-0.054	0.23	-9999	-0.85	32	32
STAT1 (dimer)	0.046	0.069	-9999	-10000	0	0
JAK2	0.014	0.004	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.047	0.038	-9999	-10000	0	0
EPO/EPOR	0.016	0.031	-9999	-10000	0	0
LYN	0.014	0.004	-9999	-10000	0	0
TEC/VAV2	0.05	0.032	-9999	-10000	0	0
elevation of cytosolic calcium ion concentration	0.011	0.039	-9999	-10000	0	0
SHC1	0.013	0	-9999	-10000	0	0
EPO/EPOR (dimer)/LYN	0.031	0.027	-9999	-10000	0	0
mol:IP3	0.045	0.042	-9999	-10000	0	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.008	0.023	-9999	-10000	0	0
SH2B3	0.014	0.004	-9999	-10000	0	0
NFKB1	0.033	0.023	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2/SOCS3	-0.024	0.079	-9999	-0.29	32	32
PTPN6	0.035	0.034	-9999	-10000	0	0
TEC/VAV2/GRB2	0.024	0.036	-9999	-10000	0	0
EPOR	0.011	0.039	-9999	-10000	0	0
INPP5D	-0.005	0.075	-9999	-0.31	23	23
mol:GDP	-0.003	0.012	-9999	-10000	0	0
SOS1	0.013	0	-9999	-10000	0	0
PLCG2	0.013	0	-9999	-10000	0	0
CRKL/CBL/C3G	0.024	0.036	-9999	-10000	0	0
VAV2	0.042	0.033	-9999	-10000	0	0
CBL	0.042	0.033	-9999	-10000	0	0
SHC/Grb2/SOS1	-0.004	0.014	-9999	-10000	0	0
STAT5A	0.047	0.057	-9999	-10000	0	0
GRB2	0.013	0	-9999	-10000	0	0
STAT5 (dimer)	0.058	0.089	-9999	-10000	0	0
LYN/PLCgamma2	0	0	-9999	-10000	0	0
PTPN11	0.013	0	-9999	-10000	0	0
BTK	0.025	0.076	-9999	-0.46	6	6
BCL2	0.014	0.26	-9999	-0.99	26	26

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.008	0.024	0.3	1	-10000	0	1
BUB1B	0.017	0.029	-10000	0	-10000	0	0
PLK1	0.017	0.01	-10000	0	-10000	0	0
PLK1S1	0.015	0.006	-10000	0	-10000	0	0
KIF2A	0.025	0.009	-10000	0	-10000	0	0
regulation of mitotic centrosome separation	0.017	0.01	-10000	0	-10000	0	0
GOLGA2	0.013	0	-10000	0	-10000	0	0
Hec1/SPC24	-0.005	0.078	-10000	0	-0.28	14	14
WEE1	0.022	0.01	-10000	0	-10000	0	0
cytokinesis	0	0.065	-10000	0	-0.31	1	1
PP2A-alpha B56	-0.015	0.02	-10000	0	-10000	0	0
AURKA	0.016	0.007	-10000	0	-10000	0	0
PICH/PLK1	0.006	0.017	-10000	0	-10000	0	0
CENPE	0.021	0.036	-10000	0	-0.52	1	1
RhoA/GTP	0	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.025	0.009	-10000	0	-10000	0	0
PPP2CA	0.013	0	-10000	0	-10000	0	0
FZR1	0.013	0	-10000	0	-10000	0	0
TPX2	0.009	0.021	-10000	0	-10000	0	0
PAK1	0.013	0	-10000	0	-10000	0	0
SPC24	-0.009	0.081	-10000	0	-0.31	27	27
FBXW11	0.013	0	-10000	0	-10000	0	0
CLSPN	0.005	0.028	-10000	0	-10000	0	0
GORASP1	0.013	0	-10000	0	-10000	0	0
metaphase	0.001	0.001	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.009	0.006	-10000	0	-0.068	1	1
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
STAG2	0.013	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.001	0.003	-10000	0	-10000	0	0
spindle elongation	0.017	0.01	-10000	0	-10000	0	0
ODF2	0.013	0.001	-10000	0	-10000	0	0
BUB1	-0.023	0.03	-10000	0	-10000	0	0
TPT1	0.015	0.006	-10000	0	-10000	0	0
CDC25C	0.011	0.023	-10000	0	-10000	0	0
CDC25B	0.011	0.028	-10000	0	-0.31	3	3
SGOL1	0.008	0.024	-10000	0	-0.3	1	1
RHOA	0.013	0	-10000	0	-10000	0	0
CCNB1/CDK1	0.006	0.014	-10000	0	-10000	0	0
CDC14B	0.006	0.068	-10000	0	-0.68	4	4
CDC20	0.009	0.036	-10000	0	-0.31	5	5
PLK1/PBIP1	0.003	0.023	-10000	0	-10000	0	0
mitosis	0	0.001	-10000	0	-0.022	1	1
FBXO5	0.022	0.008	-10000	0	-10000	0	0
CDC2	0.001	0.001	-10000	0	-10000	0	0
NDC80	-0.039	0.12	-10000	0	-0.31	65	65
metaphase plate congression	0.016	0.006	-10000	0	-10000	0	0
ERCC6L	0.007	0.017	-10000	0	-10000	0	0
NLP/gamma Tubulin	0.014	0.007	-10000	0	-10000	0	0
microtubule cytoskeleton organization	0.015	0.006	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	0	0.001	-10000	0	-0.011	1	1
PPP1R12A	0.013	0	-10000	0	-10000	0	0
interphase	0	0.001	-10000	0	-0.011	1	1
PLK1/PRC1-2	-0.003	0.066	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP/PLK1	0	0.003	-10000	0	-10000	0	0
RAB1A	0.013	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.02	0.026	-10000	0	-0.5	1	1
mitotic prometaphase	0	0.001	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.01	0.035	-10000	0	-0.33	2	2
microtubule-based process	-0.013	0.07	-10000	0	-10000	0	0
Golgi organization	0.017	0.01	-10000	0	-10000	0	0
Cohesin/SA2	-0.001	0.004	-10000	0	-10000	0	0
PPP1CB/MYPT1	0	0	-10000	0	-10000	0	0
KIF20A	-0.059	0.14	-10000	0	-0.31	90	90
APC/C/CDC20	0.021	0.022	-10000	0	-10000	0	0
PPP2R1A	0.013	0	-10000	0	-10000	0	0
chromosome segregation	0.002	0.023	-10000	0	-10000	0	0
PRC1	0.013	0	-10000	0	-10000	0	0
ECT2	0.025	0.009	-10000	0	-10000	0	0
C13orf34	0.02	0.027	-10000	0	-0.5	1	1
NUDC	0.016	0.006	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	0.017	0.029	-10000	0	-10000	0	0
spindle assembly	0.017	0.008	-10000	0	-10000	0	0
spindle stabilization	0.015	0.006	-10000	0	-10000	0	0
APC/C/HCDH1	0.013	0.059	-10000	0	-0.58	4	4
MKLP2/PLK1	-0.013	0.071	-10000	0	-10000	0	0
CCNB1	0.014	0.001	-10000	0	-10000	0	0
PPP1CB	0.013	0	-10000	0	-10000	0	0
BTRC	0.013	0	-10000	0	-10000	0	0
ROCK2	0.011	0.085	-10000	0	-0.53	10	10
TUBG1	0.015	0.006	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.01	-10000	0	-10000	0	0
MLF1IP	0.007	0.034	-10000	0	-0.22	9	9
INCENP	0.012	0.001	-10000	0	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.013	0	-9999	-10000	0	0
Rac1/GDP	0.001	0.004	-9999	-10000	0	0
DOCK1	0.009	0.06	-9999	-0.85	2	2
ITGA4	0.007	0.045	-9999	-0.31	8	8
RAC1	0.013	0	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.03	0.12	-9999	-0.64	12	12
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.003	0.022	-9999	-10000	0	0
alpha4/beta7 Integrin/Paxillin	-0.022	0.089	-9999	-0.52	11	11
lamellipodium assembly	-0.002	0.042	-9999	-0.75	1	1
PIK3CA	0.011	0.043	-9999	-0.85	1	1
PI3K	-0.002	0.032	-9999	-0.66	1	1
ARF6	0.013	0	-9999	-10000	0	0
TLN1	0.013	0	-9999	-10000	0	0
PXN	0.024	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
ARF6/GTP	-0.002	0.013	-9999	-10000	0	0
cell adhesion	-0.002	0.016	-9999	-10000	0	0
CRKL/CBL	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	-0.003	0.018	-9999	-10000	0	0
ITGB1	0.013	0	-9999	-10000	0	0
ITGB7	-0.024	0.15	-9999	-0.52	28	28
ARF6/GDP	0.001	0.004	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.008	0.048	-9999	-0.48	3	3
p130Cas/Crk/Dock1	-0.003	0.04	-9999	-0.57	2	2
VCAM1	0.002	0.083	-9999	-0.49	9	9
alpha4/beta1 Integrin/Paxillin/Talin	-0.002	0.016	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.002	0.016	-9999	-10000	0	0
BCAR1	0.013	0	-9999	-10000	0	0
mol:GDP	0.002	0.016	-9999	-10000	0	0
CBL	0.013	0	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
GIT1	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.002	0.016	-9999	-10000	0	0
Rac1/GTP	-0.002	0.05	-9999	-0.9	1	1

×

PDGFR-beta 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
S1P1/Sphingosine-1-phosphate	0.001	0.02	-9999	-10000	0	0
PDGFB-D/PDGFRB/SLAP	0	0.01	-9999	-10000	0	0
PDGFB-D/PDGFRB/APS/CBL	0	0.008	-9999	-10000	0	0
AKT1	0.061	0.032	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.025	0.034	-9999	-10000	0	0
PIK3CA	0.011	0.043	-9999	-0.85	1	1
FGR	0.003	0.012	-9999	-10000	0	0
mol:Ca2+	0.021	0.03	-9999	-10000	0	0
MYC	0.02	0.14	-9999	-0.87	10	10
SHC1	0.013	0	-9999	-10000	0	0
HRAS/GDP	0.011	0.019	-9999	-10000	0	0
LRP1/PDGFRB/PDGFB	-0.001	0.028	-9999	-0.57	1	1
GRB10	0.013	0	-9999	-10000	0	0
PTPN11	0.013	0	-9999	-10000	0	0
GO:0007205	0.021	0.03	-9999	-10000	0	0
PTEN	0.011	0.043	-9999	-0.85	1	1
GRB2	0.013	0	-9999	-10000	0	0
GRB7	-0.037	0.12	-9999	-0.31	63	63
PDGFB-D/PDGFRB/SHP2	0	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB10	0	0.001	-9999	-10000	0	0
cell cycle arrest	-0.001	0.01	-9999	-10000	0	0
HRAS	0.012	0.023	-9999	-0.31	2	2
HIF1A	0.067	0.029	-9999	-10000	0	0
GAB1	0.014	0.049	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.021	0.046	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.012	0.016	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0	0.001	-9999	-10000	0	0
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.003	0.03	-9999	-10000	0	0
positive regulation of MAPKKK cascade	0	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
mol:IP3	0.021	0.03	-9999	-10000	0	0
E5	0	0.001	-9999	-10000	0	0
CSK	0.013	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.031	0.074	-9999	-10000	0	0
SHB	0.013	0	-9999	-10000	0	0
BLK	-0.19	0.28	-9999	-0.62	123	123
PTPN2	0.013	0.002	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0	0.001	-9999	-10000	0	0
BCAR1	0.013	0	-9999	-10000	0	0
VAV2	0.018	0.057	-9999	-10000	0	0
CBL	0.013	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0	0.001	-9999	-10000	0	0
LCK	-0.006	0.07	-9999	-0.62	5	5
PDGFRB	0.014	0.002	-9999	-10000	0	0
ACP1	0.013	0	-9999	-10000	0	0
HCK	0.007	0.024	-9999	-10000	0	0
ABL1	0.01	0.048	-9999	-10000	0	0
PDGFB-D/PDGFRB/CBL	0.01	0.052	-9999	-10000	0	0
PTPN1	0.013	0.002	-9999	-10000	0	0
SNX15	0.013	0	-9999	-10000	0	0
STAT3	0.013	0	-9999	-10000	0	0
STAT1	0.006	0.048	-9999	-0.31	9	9
cell proliferation	0.022	0.13	-9999	-0.75	10	10
SLA	0.012	0.016	-9999	-0.31	1	1
actin cytoskeleton reorganization	0.021	0.026	-9999	-10000	0	0
SRC	0.006	0.012	-9999	-10000	0	0
PI3K	-0.002	0.03	-9999	-0.42	1	1
PDGFB-D/PDGFRB/GRB7/SHC	-0.024	0.057	-9999	-10000	0	0
SH2B2	0.012	0.016	-9999	-0.31	1	1
PLCgamma1/SPHK1	0.025	0.034	-9999	-10000	0	0
LYN	0.007	0.013	-9999	-10000	0	0
LRP1	0.011	0.043	-9999	-0.85	1	1
SOS1	0.013	0	-9999	-10000	0	0
STAT5B	0.013	0	-9999	-10000	0	0
STAT5A	0.013	0	-9999	-10000	0	0
NCK1-2/p130 Cas	0.001	0.007	-9999	-10000	0	0
SPHK1	0.007	0.045	-9999	-0.31	8	8
EDG1	0.001	0.001	-9999	-10000	0	0
mol:DAG	0.021	0.03	-9999	-10000	0	0
PLCG1	0.022	0.03	-9999	-10000	0	0
NHERF/PDGFRB	-0.001	0.011	-9999	-10000	0	0
YES1	0.005	0.01	-9999	-10000	0	0
cell migration	-0.001	0.011	-9999	-10000	0	0
SHC/Grb2/SOS1	0.001	0.007	-9999	-10000	0	0
SLC9A3R2	0.013	0	-9999	-10000	0	0
SLC9A3R1	0.012	0.023	-9999	-0.31	2	2
NHERF1-2/PDGFRB/PTEN	-0.002	0.027	-9999	-0.52	1	1
FYN	0.007	0.012	-9999	-10000	0	0
DOK1	0.035	0.006	-9999	-10000	0	0
HRAS/GTP	-0.001	0.015	-9999	-0.21	2	2
PDGFB	0.013	0	-9999	-10000	0	0
RAC1	0.029	0.078	-9999	-0.4	10	10
PRKCD	0.035	0.006	-9999	-10000	0	0
FER	0.033	0.04	-9999	-0.53	2	2
MAPKKK cascade	0	0.006	-9999	-10000	0	0
RASA1	0.035	0.006	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
NCK2	0.013	0	-9999	-10000	0	0
p62DOK/Csk	0.016	0.02	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHB	0	0.001	-9999	-10000	0	0
chemotaxis	0.01	0.047	-9999	-10000	0	0
STAT1-3-5/STAT1-3-5	-0.002	0.013	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0.003	0.004	-9999	-10000	0	0
PTPRJ	0.013	0	-9999	-10000	0	0

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	-0.002	0.03	-9999	-0.43	2	2
TRAF2/ASK1	-0.001	0.029	-9999	-0.58	1	1
ATM	0.011	0.043	-9999	-0.85	1	1
MAP2K3	0.028	0.057	-9999	-0.54	2	2
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.028	0.074	-9999	-0.43	5	5
hyperosmotic response	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
GADD45G	-0.002	0.11	-9999	-0.67	9	9
TXN	0.009	0.007	-9999	-10000	0	0
CALM1	0.013	0	-9999	-10000	0	0
GADD45A	0.013	0	-9999	-10000	0	0
GADD45B	-0.021	0.17	-9999	-0.85	16	16
MAP3K1	0.013	0	-9999	-10000	0	0
MAP3K6	0.013	0	-9999	-10000	0	0
MAP3K7	0.013	0	-9999	-10000	0	0
MAP3K4	0.013	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
ASK1/ASK2	-0.002	0.032	-9999	-0.66	1	1
TAK1/TAB family	-0.001	0.011	-9999	-0.22	1	1
RAC1/OSM/MEKK3	0	0	-9999	-10000	0	0
TRAF2	0.013	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.007	0.033	-9999	-0.39	2	2
TRAF6	0.008	0.024	-9999	-0.47	1	1
RAC1	0.013	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
CAMK2B	0.003	0.095	-9999	-0.85	5	5
CCM2	0.013	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.007	0.064	-9999	-0.58	5	5
MAPK11	0.013	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.008	0.072	-9999	-0.63	5	5
OSM/MEKK3	0	0	-9999	-10000	0	0
TAOK1	-0.029	0.15	-9999	-0.48	39	39
TAOK2	0.017	0.024	-9999	-0.46	1	1
TAOK3	0.017	0.024	-9999	-0.46	1	1
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.013	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
MAP3K5	0.011	0.043	-9999	-0.85	1	1
MAP3K10	0.013	0	-9999	-10000	0	0
MAP3K3	0.013	0	-9999	-10000	0	0
TRX/ASK1	0.015	0.029	-9999	-0.57	1	1
GADD45/MTK1/MTK1	-0.027	0.12	-9999	-0.52	21	21

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.013	0	-9999	-10000	0	0
SMAD2	0.015	0	-9999	-10000	0	0
SMAD3	0.044	0	-9999	-10000	0	0
SMAD3/SMAD4	0.05	0	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	0	0	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	0	0	-9999	-10000	0	0
PPM1A	0.013	0	-9999	-10000	0	0
CALM1	0.013	0	-9999	-10000	0	0
SMAD2/SMAD4	0.022	0	-9999	-10000	0	0
MAP3K1	0.013	0	-9999	-10000	0	0
TRAP-1/SMAD4	-0.031	0.14	-9999	-0.66	19	19
MAPK3	0.013	0	-9999	-10000	0	0
MAPK1	0.013	0	-9999	-10000	0	0
NUP214	0.013	0	-9999	-10000	0	0
CTDSP1	0.013	0	-9999	-10000	0	0
CTDSP2	0.013	0	-9999	-10000	0	0
CTDSPL	0.013	0	-9999	-10000	0	0
KPNB1	0.013	0	-9999	-10000	0	0
TGFBRAP1	-0.027	0.18	-9999	-0.85	19	19
UBE2I	0.013	0	-9999	-10000	0	0
NUP153	0.013	0	-9999	-10000	0	0
KPNA2	0.013	0	-9999	-10000	0	0
PIAS4	0.013	0	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0	0	-9999	-10000	0	0
HDAC3	0.013	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC5	0	0	-9999	-10000	0	0
GATA2/HDAC5	0	0.01	-9999	-10000	0	0
HDAC5/BCL6/BCoR	-0.001	0.028	-9999	-0.57	1	1
HDAC9	-0.017	0.095	-9999	-0.31	38	38
Glucocorticoid receptor/Hsp90/HDAC6	0	0	-9999	-10000	0	0
HDAC4/ANKRA2	0	0	-9999	-10000	0	0
HDAC5/YWHAB	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.023	0	-9999	-10000	0	0
GATA2	0.012	0.016	-9999	-0.31	1	1
HDAC4/RFXANK	0	0.01	-9999	-10000	0	0
BCOR	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.013	0	-9999	-10000	0	0
HDAC5	0.013	0	-9999	-10000	0	0
GNB1/GNG2	0	0	-9999	-10000	0	0
Histones	0.036	0.023	-9999	-10000	0	0
ADRBK1	0.013	0	-9999	-10000	0	0
HDAC4	0.013	0	-9999	-10000	0	0
XPO1	0.013	0	-9999	-10000	0	0
HDAC5/ANKRA2	0	0	-9999	-10000	0	0
HDAC4/Ubc9	0	0	-9999	-10000	0	0
HDAC7	0.013	0	-9999	-10000	0	0
HDAC5/14-3-3 E	0	0	-9999	-10000	0	0
TUBA1B	0.013	0	-9999	-10000	0	0
HDAC6	0.013	0	-9999	-10000	0	0
HDAC5/RFXANK	0	0.01	-9999	-10000	0	0
CAMK4	-0.003	0.097	-9999	-0.48	13	13
Tubulin/HDAC6	-0.004	0.049	-9999	-0.57	3	3
SUMO1	0.013	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.013	0	-9999	-10000	0	0
GATA1	0.009	0.006	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
NR3C1	0.013	0	-9999	-10000	0	0
SUMO1/HDAC4	0	0	-9999	-10000	0	0
SRF	0.013	0	-9999	-10000	0	0
HDAC4/YWHAB	0	0	-9999	-10000	0	0
Tubulin	-0.005	0.056	-9999	-0.66	3	3
HDAC4/14-3-3 E	0	0	-9999	-10000	0	0
GNB1	0.013	0	-9999	-10000	0	0
RANGAP1	0.013	0	-9999	-10000	0	0
BCL6/BCoR	-0.002	0.032	-9999	-0.66	1	1
HDAC4/HDAC3/SMRT (N-CoR2)	0	0	-9999	-10000	0	0
HDAC4/SRF	-0.009	0.06	-9999	-0.57	4	4
HDAC4/ER alpha	-0.044	0.14	-9999	-0.66	19	19
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.035	0.023	-9999	-10000	0	0
cell motility	-0.004	0.048	-9999	-0.57	3	3
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.013	0	-9999	-10000	0	0
HDAC7/HDAC3	0	0	-9999	-10000	0	0
BCL6	0.011	0.043	-9999	-0.85	1	1
HDAC4/CaMK II delta B	0.013	0	-9999	-10000	0	0
Hsp90/HDAC6	0	0	-9999	-10000	0	0
ESR1	-0.049	0.2	-9999	-0.85	19	19
HDAC6/HDAC11	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
MEF2C	0.013	0	-9999	-10000	0	0
RAN	0.013	0	-9999	-10000	0	0
HDAC4/MEF2C	0	0	-9999	-10000	0	0
GNG2	0.013	0	-9999	-10000	0	0
NCOR2	0.013	0	-9999	-10000	0	0
TUBB2A	0.007	0.074	-9999	-0.85	3	3
HDAC11	0.013	0	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
RANBP2	0.013	0	-9999	-10000	0	0
ANKRA2	0.013	0	-9999	-10000	0	0
RFXANK	0.012	0.016	-9999	-0.31	1	1
nuclear import	0	0	-9999	-10000	0	0

×

HIF-2-alpha transcription factor network

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
MMP14	-0.001	0.024	-9999	-10000	0	0
oxygen homeostasis	0.015	0.011	-9999	-10000	0	0
TCEB2	0.012	0.016	-9999	-0.31	1	1
TCEB1	0.013	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.008	0.043	-9999	-0.52	1	1
EPO	0.19	0.12	-9999	-10000	0	0
FIH (dimer)	0.028	0.011	-9999	-10000	0	0
APEX1	0.026	0.011	-9999	-10000	0	0
SERPINE1	0.18	0.16	-9999	-0.65	1	1
FLT1	0.001	0.016	-9999	-10000	0	0
ADORA2A	0.19	0.13	-9999	-10000	0	0
germ cell development	0.19	0.13	-9999	-10000	0	0
SLC11A2	0.19	0.13	-9999	-10000	0	0
BHLHE40	0.18	0.15	-9999	-10000	0	0
HIF1AN	0.028	0.011	-9999	-10000	0	0
HIF2A/ARNT/SIRT1	0.001	0.043	-9999	-10000	0	0
ETS1	0.03	0.003	-9999	-10000	0	0
CITED2	-0.086	0.31	-9999	-1.2	30	30
KDR	-0.007	0.11	-9999	-1.3	3	3
PGK1	0.19	0.13	-9999	-10000	0	0
SIRT1	0.013	0.001	-9999	-10000	0	0
response to hypoxia	0	0.001	-9999	-10000	0	0
HIF2A/ARNT	0.21	0.14	-9999	-10000	0	0
EPAS1	0.11	0.089	-9999	-10000	0	0
SP1	0.021	0.002	-9999	-10000	0	0
ABCG2	0.19	0.14	-9999	-0.76	2	2
EFNA1	0.19	0.13	-9999	-10000	0	0
FXN	0.19	0.13	-9999	-10000	0	0
POU5F1	0.19	0.13	-9999	-10000	0	0
neuron apoptosis	-0.2	0.14	-9999	-10000	0	0
EP300	0.013	0	-9999	-10000	0	0
EGLN3	-0.007	0.15	-9999	-0.57	20	20
EGLN2	0.028	0.011	-9999	-10000	0	0
EGLN1	0.028	0.011	-9999	-10000	0	0
VHL/Elongin B/Elongin C	-0.003	0.04	-9999	-0.57	2	2
VHL	0.009	0.06	-9999	-0.85	2	2
ARNT	0.027	0.011	-9999	-10000	0	0
SLC2A1	0.19	0.13	-9999	-10000	0	0
TWIST1	0.18	0.17	-9999	-0.63	8	8
ELK1	0.014	0.027	-9999	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.002	0.042	-9999	-10000	0	0
VEGFA	0.19	0.14	-9999	-0.69	2	2
CREBBP	0.013	0	-9999	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	0.032	0	-9999	-10000	0	0
SNTA1	0.013	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.032	0.009	-9999	-10000	0	0
MAPK12	0.024	0.067	-9999	-0.52	6	6
CCND1	0.018	0.03	-9999	-0.26	1	1
p38 gamma/SNTA1	0.029	0.063	-9999	-0.48	6	6
MAP2K3	0.013	0	-9999	-10000	0	0
PKN1	0.013	0	-9999	-10000	0	0
G2/M transition checkpoint	0.024	0.067	-9999	-0.51	6	6
MAP2K6	0.017	0.071	-9999	-0.56	6	6
MAPT	0.026	0.041	-9999	-0.41	2	2
MAPK13	0.024	0	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.018	0	-9999	-10000	0	0

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.052	0.025	-10000	0	-0.46	1	1
adherens junction organization	0.044	0.032	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.052	0.055	-10000	0	-10000	0	0
FMN1	0.029	0.097	-10000	0	-0.46	15	15
mol:IP3	-0.001	0.021	-10000	0	-0.43	1	1
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.04	0.008	-10000	0	-10000	0	0
CTNNB1	0.013	0	-10000	0	-10000	0	0
AKT1	0.051	0.023	-10000	0	-0.42	1	1
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.046	0.006	-10000	0	-10000	0	0
CTNND1	0.014	0.001	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.046	0.025	-10000	0	-0.44	1	1
VASP	0.047	0.007	-10000	0	-10000	0	0
ZYX	0.047	0.007	-10000	0	-10000	0	0
JUB	0.046	0.026	-10000	0	-0.46	1	1
EGFR(dimer)	0.04	0.055	-10000	0	-0.45	5	5
E-cadherin/beta catenin-gamma catenin	0	0.002	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.022	-10000	0	-0.45	1	1
PIK3CA	0.012	0.043	-10000	0	-0.85	1	1
PI3K	-0.001	0.023	-10000	0	-0.46	1	1
FYN	0.052	0.026	-10000	0	-10000	0	0
mol:Ca2+	-0.001	0.021	-10000	0	-0.42	1	1
JUP	0.013	0	-10000	0	-10000	0	0
PIK3R1	0.014	0.001	-10000	0	-10000	0	0
mol:DAG	-0.001	0.021	-10000	0	-0.43	1	1
CDH1	0.013	0	-10000	0	-10000	0	0
RhoA/GDP	0.052	0.055	-10000	0	-10000	0	0
establishment of polarity of embryonic epithelium	0.047	0.007	-10000	0	-10000	0	0
SRC	0.012	0.016	-10000	0	-0.31	1	1
RAC1	0.013	0	-10000	0	-10000	0	0
RHOA	0.013	0	-10000	0	-10000	0	0
EGFR	0.003	0.095	-10000	0	-0.85	5	5
CASR	0.044	0.028	-10000	0	-0.4	1	1
RhoA/GTP	-0.001	0.019	-10000	0	-0.38	1	1
AKT2	0.051	0.023	-10000	0	-0.42	1	1
actin cable formation	0.036	0.094	-10000	0	-0.44	15	15
apoptosis	0.001	0.021	0.43	1	-10000	0	1
CTNNA1	0.014	0.001	-10000	0	-10000	0	0
mol:GDP	0.047	0.058	-10000	0	-0.43	6	6
PIP5K1A	0.046	0.026	-10000	0	-0.46	1	1
PLCG1	-0.001	0.022	-10000	0	-0.44	1	1
Rac1/GTP	-0.005	0.046	-10000	0	-0.41	5	5
homophilic cell adhesion	0.001	0.001	-10000	0	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
HDAC1	0.013	-9999	-9999
Ran/GTP/Exportin 1/HDAC4	0	-9999	-9999
MDM2/SUMO1	0	-9999	-9999
HDAC4	0.013	-9999	-9999
Ran/GTP/Exportin 1/HDAC1	0	-9999	-9999
SUMO1	0.013	-9999	-9999
NPC/RanGAP1/SUMO1	0.018	-9999	-9999
mol:GTP	0	-9999	-9999
XPO1	0.031	-9999	-9999
EntrezGene:23636	0	-9999	-9999
RAN	0.013	-9999	-9999
EntrezGene:8021	0	-9999	-9999
RANBP2	0.013	-9999	-9999
SUMO1/HDAC4	0	-9999	-9999
SUMO1/HDAC1	0	-9999	-9999
RANGAP1	0.013	-9999	-9999
MDM2/SUMO1/SUMO1	0	-9999	-9999
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.023	-9999	-9999
Ran/GTP	0	-9999	-9999
EntrezGene:23225	0	-9999	-9999
MDM2	0.013	-9999	-9999
UBE2I	0.013	-9999	-9999
Ran/GTP/Exportin 1	0	-9999	-9999
NPC	0	-9999	-9999
PIAS2	0.013	-9999	-9999
PIAS1	0.013	-9999	-9999
EntrezGene:9972	0	-9999	-9999

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.023	0.17	-10000	0	-0.77	19	19
CLTC	0.034	0	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.029	0	-10000	0	-10000	0	0
Dynamin 2/GTP	0	0	-10000	0	-10000	0	0
EXOC4	0.013	0	-10000	0	-10000	0	0
CD59	0.031	0	-10000	0	-10000	0	0
CPE	0.01	0.078	-10000	0	-0.58	7	7
CTNNB1	0.013	0	-10000	0	-10000	0	0
membrane fusion	0	0	-10000	0	-10000	0	0
CTNND1	0.034	0	-10000	0	-10000	0	0
DNM2	0.013	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.035	0	-10000	0	-10000	0	0
TSHR	0.017	0.042	-10000	0	-0.58	2	2
INS	0.013	0	-10000	0	-10000	0	0
BIN1	0.013	0	-10000	0	-10000	0	0
mol:Choline	0	0	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.02	0	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.013	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
JUP	0.031	0	-10000	0	-10000	0	0
ASAP2/amphiphysin II	-0.001	0.026	-10000	0	-0.53	1	1
ARF6/GTP	0	0	-10000	0	-10000	0	0
CDH1	0.031	0	-10000	0	-10000	0	0
clathrin-independent pinocytosis	0	0	-10000	0	-10000	0	0
MAPK8IP3	0.013	0	-10000	0	-10000	0	0
positive regulation of endocytosis	0	0	-10000	0	-10000	0	0
EXOC2	0.013	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.046	0	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.013	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0	0	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.02	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0	0	-10000	0	-10000	0	0
ACAP1	0.026	0.01	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.025	0.001	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.04	0.002	-10000	0	-10000	0	0
JIP4/KLC1	0	0	-10000	0	-10000	0	0
EXOC1	0.013	0	-10000	0	-10000	0	0
exocyst	0.046	0	-10000	0	-10000	0	0
RALA/GTP	0	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0	0	-10000	0	-10000	0	0
receptor recycling	0	0	-10000	0	-10000	0	0
CTNNA1	0.034	0	-10000	0	-10000	0	0
NME1	0.02	0	-10000	0	-10000	0	0
clathrin coat assembly	0.034	0	-10000	0	-10000	0	0
IL2RA	0.012	0.069	-10000	0	-10000	0	0
VAMP3	0.02	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.017	0.083	-10000	0	-0.43	16	16
EXOC6	0.013	0	-10000	0	-10000	0	0
PLD1	0	0	-10000	0	-10000	0	0
PLD2	0	0	-10000	0	-10000	0	0
EXOC5	0.013	0	-10000	0	-10000	0	0
PIP5K1C	0.035	0	-10000	0	-10000	0	0
SDC1	0.03	0.007	-10000	0	-10000	0	0
ARF6/GDP	0.019	0	-10000	0	-10000	0	0
EXOC7	0.013	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0	0	-10000	0	-10000	0	0
endocytosis	0.001	0.026	0.52	1	-10000	0	1
SCAMP2	0.013	0	-10000	0	-10000	0	0
ADRB2	0.029	0.077	-10000	0	-0.46	10	10
EXOC3	0.013	0	-10000	0	-10000	0	0
ASAP2	0.011	0.043	-10000	0	-0.85	1	1
Dynamin 2/GDP	0.026	0	-10000	0	-10000	0	0
KLC1	0.013	0	-10000	0	-10000	0	0
AVPR2	0.031	0.07	-10000	0	-0.46	8	8
RALA	0.013	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0	0	-10000	0	-10000	0	0

×

E-cadherin signaling events

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

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

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
E-cadherin/beta catenin-gamma catenin	0	-9999	-9999
E-cadherin/beta catenin	0	-9999	-9999
CTNNB1	0.013	-9999	-9999
JUP	0.013	-9999	-9999
CDH1	0.013	-9999	-9999

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0	0.001	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.021	0.012	-9999	-0.21	1	1
AP2	0	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0.003	-9999	-10000	0	0
CLTB	0.013	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.027	0	-9999	-10000	0	0
CD4	0.004	0.055	-9999	-0.31	12	12
CLTA	0.013	0	-9999	-10000	0	0
mol:GTP	0.002	0.001	-9999	-10000	0	0
ARFGAP1	0.012	0	-9999	-10000	0	0
mol:PI-4-5-P2	-0.001	0.022	-9999	-0.44	1	1
ARF1/GTP	-0.001	0.013	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.029	0	-9999	-10000	0	0
mol:Choline	-0.001	0.021	-9999	-0.44	1	1
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.013	0	-9999	-10000	0	0
DDEF1	-0.001	0.022	-9999	-0.44	1	1
ARF1/GDP	0	0.006	-9999	-10000	0	0
AP2M1	0.013	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0	0.001	-9999	-10000	0	0
Rac/GTP	0	0.001	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0	0.002	-9999	-10000	0	0
ARFIP2	0	0.004	-9999	-10000	0	0
COPA	0.013	0	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.027	0.006	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0.001	-9999	-10000	0	0
GGA3	0.013	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0	0.008	-9999	-10000	0	0
AP2A1	0.013	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.029	0	-9999	-10000	0	0
ARF1/GDP/Membrin	0	0.007	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0	0.003	-9999	-10000	0	0
CYTH2	0.013	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0	0.002	-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	0.036	0.014	-9999	-10000	0	0
PLD2	-0.001	0.022	-9999	-0.44	1	1
ARF-GAP1/v-SNARE	0.012	0	-9999	-10000	0	0
PIP5K1A	-0.001	0.022	-9999	-0.44	1	1
ARF1/GTP/Membrin/GBF1/p115	-0.001	0.012	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.001	0.021	-9999	-0.44	1	1
KDEL Receptor/Ligand/ARF-GAP1	0.012	0	-9999	-10000	0	0
GOSR2	0	0.009	-9999	-10000	0	0
USO1	0	0.009	-9999	-10000	0	0
GBF1	0	0.009	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0	0.003	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	-0.005	0.026	-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	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
IKK alpha homodimer	0	-9999	-9999
FBXW11	0.013	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	0	-9999	-9999
beta TrCP1/SCF ubiquitin ligase complex	0.013	-9999	-9999
CHUK	0.013	-9999	-9999
NF kappa B2 p100/RelB	0	-9999	-9999
NFKB1	0.013	-9999	-9999
MAP3K14	0.013	-9999	-9999
NF kappa B1 p50/RelB	0	-9999	-9999
RELB	0.013	-9999	-9999
NFKB2	0.013	-9999	-9999
NF kappa B2 p52/RelB	0	-9999	-9999
regulation of B cell activation	0	-9999	-9999

pid_entity	TCGA.KS.A41L	TCGA.KS.A41J	TCGA.KS.A41I	TCGA.KS.A41F
109_MAP3K5	-0.22	-0.28	0.058	-0.22
47_PPARGC1A	0.013	-0.85	0.013	-0.85
105_BMP4	0.013	0.013	0.013	0.013
105_BMP6	0.013	0.013	0.013	0.013
105_BMP7	0.013	0.013	0.013	0.013
105_BMP2	0.013	0.013	0.013	0.013
131_RELN/VLDLR	0	-0.52	0	-0.52
30_TGFB1/TGF beta receptor Type II	0.013	0.013	0.013	0.013
84_STAT5B	0.045	0.0028	0	-0.053
84_STAT5A	0.045	0.0028	0	-0.053