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

Pathway.Name	Avg.Num.Perturbations
Angiopoietin receptor Tie2-mediated signaling	159
Signaling events mediated by the Hedgehog family	137
Endothelins	96
Fc-epsilon receptor I signaling in mast cells	66
Thromboxane A2 receptor signaling	61
amb2 Integrin signaling	57
IL4-mediated signaling events	56
Signaling mediated by p38-alpha and p38-beta	56
TCGA08_retinoblastoma	56
Aurora B signaling	55

Pathway.Name	Significance.Ratio	Avg.Num.Perturbations	Total.Perturbations	Num.Entities	Min.Mean.Truth	Max.Mean.Truth	Min.Mean.Within	Max.Mean.Within	Min.Mean.Any	Max.Mean.Within.1
Angiopoietin receptor Tie2-mediated signaling	0.3174	159	14075	88	-0.68	0.075	1000	-1000	-0.062	-1000
Signaling events mediated by the Hedgehog family	0.2735	137	7159	52	-0.41	0.21	1000	-1000	-0.036	-1000
Endothelins	0.1916	96	9262	96	-0.37	0.1	1000	-1000	-0.054	-1000
Fc-epsilon receptor I signaling in mast cells	0.1317	66	6427	97	-0.14	0.023	1000	-1000	-0.064	-1000
Thromboxane A2 receptor signaling	0.1218	61	6490	105	-0.21	0.057	1000	-1000	-0.051	-1000
amb2 Integrin signaling	0.1138	57	4708	82	-0.48	0.035	1000	-1000	-0.039	-1000
IL4-mediated signaling events	0.1118	56	5122	91	-0.81	0.5	1000	-1000	-0.16	-1000
Signaling mediated by p38-alpha and p38-beta	0.1118	56	2502	44	-0.1	0.022	1000	-1000	-0.034	-1000
TCGA08_retinoblastoma	0.1118	56	454	8	-0.009	0.092	1000	-1000	-0.002	-1000
Aurora B signaling	0.1098	55	3689	67	-0.3	0.28	1000	-1000	-0.05	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.1038	52	2754	52	-0.25	0.048	1000	-1000	-0.048	-1000
Aurora C signaling	0.1018	51	361	7	-0.004	0.15	1000	-1000	-0.013	-1000
Signaling events regulated by Ret tyrosine kinase	0.0878	44	3683	82	-0.11	0.054	1000	-1000	-0.059	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0778	39	3064	78	-0.16	0.051	1000	-1000	-0.053	-1000
Nongenotropic Androgen signaling	0.0758	38	1978	52	-0.12	0.076	1000	-1000	-0.038	-1000
BMP receptor signaling	0.0739	37	3070	81	-0.26	0.15	1000	-1000	-0.049	-1000
Integrins in angiogenesis	0.0719	36	3090	84	-0.31	0.12	1000	-1000	-0.043	-1000
Calcium signaling in the CD4+ TCR pathway	0.0719	36	1121	31	-0.16	0.024	1000	-1000	-0.04	-1000
Arf6 signaling events	0.0679	34	2115	62	-0.13	0.043	1000	-1000	-0.035	-1000
PLK1 signaling events	0.0659	33	2811	85	-0.026	0.16	1000	-1000	-0.031	-1000
Canonical Wnt signaling pathway	0.0619	31	1615	51	-0.32	0.15	1000	-1000	-0.051	-1000
IL6-mediated signaling events	0.0599	30	2295	75	-0.46	0.048	1000	-1000	-0.058	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0579	29	2023	68	-0.17	0.039	1000	-1000	-0.079	-1000
Coregulation of Androgen receptor activity	0.0559	28	2178	76	-0.32	0.091	1000	-1000	-0.029	-1000
Reelin signaling pathway	0.0559	28	1592	56	-0.065	0.059	1000	-1000	-0.047	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0539	27	3401	125	-0.12	0.05	1000	-1000	-0.058	-1000
Presenilin action in Notch and Wnt signaling	0.0519	26	1646	61	-0.32	0.15	1000	-1000	-0.057	-1000
Glypican 2 network	0.0519	26	106	4	0.027	0.056	1000	-1000	0.012	-1000
Visual signal transduction: Cones	0.0499	25	987	38	-0.036	0.12	1000	-1000	-0.028	-1000
LPA4-mediated signaling events	0.0479	24	292	12	-0.093	0	1000	-1000	-0.026	-1000
HIF-1-alpha transcription factor network	0.0479	24	1860	76	-0.12	0.12	1000	-1000	-0.11	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0479	24	2076	85	-0.11	0.031	1000	-1000	-0.049	-1000
IL12-mediated signaling events	0.0459	23	2031	87	-0.16	0.044	1000	-1000	-0.084	-1000
TCR signaling in naïve CD8+ T cells	0.0459	23	2211	93	-0.061	0.032	1000	-1000	-0.047	-1000
IL23-mediated signaling events	0.0459	23	1393	60	-0.2	0.025	1000	-1000	-0.13	-1000
Plasma membrane estrogen receptor signaling	0.0459	23	2021	86	-0.11	0.037	1000	-1000	-0.053	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0459	23	779	33	-0.16	0.091	1000	-1000	-0.034	-1000
Regulation of Androgen receptor activity	0.0459	23	1628	70	-0.35	0.14	1000	-1000	-0.042	-1000
Glucocorticoid receptor regulatory network	0.0439	22	2583	114	-0.33	0.063	1000	-1000	-0.053	-1000
Syndecan-1-mediated signaling events	0.0419	21	743	34	-0.09	0.15	1000	-1000	-0.051	-1000
Nectin adhesion pathway	0.0419	21	1351	63	-0.031	0.12	1000	-1000	-0.046	-1000
Wnt signaling	0.0419	21	151	7	0.007	0.054	1000	-1000	-0.011	-1000
FOXM1 transcription factor network	0.0419	21	1076	51	0.022	0.31	1000	-1000	-0.13	-1000
ErbB4 signaling events	0.0399	20	1397	69	-0.13	0.16	1000	-1000	-0.054	-1000
Glypican 1 network	0.0399	20	976	48	-0.14	0.082	1000	-1000	-0.036	-1000
TCGA08_p53	0.0399	20	141	7	-0.032	0.022	1000	-1000	-0.015	-1000
Caspase cascade in apoptosis	0.0359	18	1336	74	-0.063	0.082	1000	-1000	-0.037	-1000
S1P1 pathway	0.0359	18	662	36	-0.1	0.022	1000	-1000	-0.042	-1000
FAS signaling pathway (CD95)	0.0359	18	847	47	-0.19	0.059	1000	-1000	-0.041	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0359	18	2180	120	-0.14	0.06	1000	-1000	-0.045	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0339	17	941	54	-0.065	0.071	1000	-1000	-0.05	-1000
JNK signaling in the CD4+ TCR pathway	0.0339	17	301	17	-0.037	0.032	1000	-1000	-0.031	-1000
Visual signal transduction: Rods	0.0319	16	860	52	-0.036	0.092	1000	-1000	-0.036	-1000
Noncanonical Wnt signaling pathway	0.0299	15	408	26	-0.051	0.054	1000	-1000	-0.043	-1000
PDGFR-alpha signaling pathway	0.0299	15	666	44	-0.12	0.044	1000	-1000	-0.042	-1000
Syndecan-3-mediated signaling events	0.0299	15	535	35	-0.24	0.055	1000	-1000	-0.034	-1000
p75(NTR)-mediated signaling	0.0279	14	1867	125	-0.046	0.14	1000	-1000	-0.078	-1000
Ephrin B reverse signaling	0.0279	14	681	48	-0.057	0.062	1000	-1000	-0.03	-1000
BCR signaling pathway	0.0279	14	1386	99	-0.093	0.052	1000	-1000	-0.045	-1000
Osteopontin-mediated events	0.0259	13	506	38	-0.048	0.12	1000	-1000	-0.051	-1000
Signaling events mediated by PTP1B	0.0259	13	1032	76	-0.044	0.058	1000	-1000	-0.035	-1000
Effects of Botulinum toxin	0.0259	13	346	26	-0.031	0.029	1000	-1000	-0.014	-1000
EGFR-dependent Endothelin signaling events	0.0259	13	276	21	-0.025	0.049	1000	-1000	-0.04	-1000
S1P4 pathway	0.0259	13	333	25	-0.026	0.032	1000	-1000	-0.028	-1000
Aurora A signaling	0.0240	12	760	60	-0.037	0.2	1000	-1000	-0.028	-1000
HIF-2-alpha transcription factor network	0.0240	12	523	43	-0.07	0.064	1000	-1000	-0.065	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0240	12	900	74	-0.14	0.048	1000	-1000	-0.07	-1000
IGF1 pathway	0.0240	12	728	57	-0.053	0.056	1000	-1000	-0.048	-1000
Ras signaling in the CD4+ TCR pathway	0.0240	12	219	17	-0.02	0.03	1000	-1000	-0.031	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0220	11	330	28	-0.11	0.043	1000	-1000	-0.03	-1000
Hedgehog signaling events mediated by Gli proteins	0.0220	11	725	65	-0.51	0.055	1000	-1000	-0.056	-1000
Syndecan-2-mediated signaling events	0.0200	10	731	69	-0.028	0.082	1000	-1000	-0.04	-1000
Syndecan-4-mediated signaling events	0.0200	10	713	67	-0.032	0.082	1000	-1000	-0.046	-1000
Regulation of nuclear SMAD2/3 signaling	0.0180	9	1322	136	-0.22	0.14	1000	-1000	-0.045	-1000
LPA receptor mediated events	0.0180	9	945	102	-0.06	0.041	1000	-1000	-0.068	-1000
ErbB2/ErbB3 signaling events	0.0160	8	581	65	-0.036	0.033	1000	-1000	-0.053	-1000
Cellular roles of Anthrax toxin	0.0160	8	348	39	-0.06	0.023	1000	-1000	-0.027	-1000
mTOR signaling pathway	0.0160	8	456	53	-0.017	0.092	1000	-1000	-0.036	-1000
Retinoic acid receptors-mediated signaling	0.0160	8	505	58	-0.15	0.045	1000	-1000	-0.055	-1000
IL2 signaling events mediated by PI3K	0.0160	8	482	58	-0.019	0.12	1000	-1000	-0.043	-1000
EPHB forward signaling	0.0160	8	741	85	-0.043	0.07	1000	-1000	-0.066	-1000
IL27-mediated signaling events	0.0160	8	421	51	-0.062	0.029	1000	-1000	-0.057	-1000
IL2 signaling events mediated by STAT5	0.0160	8	184	22	0.003	0.074	1000	-1000	-0.047	-1000
PDGFR-beta signaling pathway	0.0160	8	808	97	-0.045	0.064	1000	-1000	-0.059	-1000
FOXA2 and FOXA3 transcription factor networks	0.0140	7	356	46	-0.23	0.045	1000	-1000	-0.11	-1000
Regulation of p38-alpha and p38-beta	0.0140	7	422	54	-0.035	0.052	1000	-1000	-0.047	-1000
TCGA08_rtk_signaling	0.0140	7	193	26	-0.063	0.081	1000	-1000	-0.01	-1000
Insulin Pathway	0.0140	7	518	74	-0.082	0.059	1000	-1000	-0.065	-1000
Ephrin A reverse signaling	0.0120	6	43	7	-0.011	0.029	1000	-1000	-0.016	-1000
IFN-gamma pathway	0.0120	6	444	68	-0.03	0.064	1000	-1000	-0.068	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0120	6	578	83	-0.063	0.041	1000	-1000	-0.042	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0120	6	302	45	-0.018	0.051	1000	-1000	-0.055	-1000
Class I PI3K signaling events	0.0120	6	484	73	-0.029	0.042	1000	-1000	-0.042	-1000
S1P3 pathway	0.0120	6	293	42	-0.11	0.042	1000	-1000	-0.041	-1000
Signaling events mediated by PRL	0.0120	6	234	34	-0.034	0.064	1000	-1000	-0.044	-1000
E-cadherin signaling in keratinocytes	0.0120	6	296	43	-0.049	0.063	1000	-1000	-0.037	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0100	5	194	34	-0.031	0.05	1000	-1000	-0.031	-1000
EPO signaling pathway	0.0100	5	296	55	-0.01	0.06	1000	-1000	-0.046	-1000
Ceramide signaling pathway	0.0100	5	448	76	-0.011	0.059	1000	-1000	-0.036	-1000
Signaling events mediated by HDAC Class III	0.0100	5	207	40	-0.076	0.041	1000	-1000	-0.028	-1000
ceramide signaling pathway	0.0100	5	260	49	0	0.033	1000	-1000	-0.039	-1000
Signaling events mediated by HDAC Class II	0.0080	4	326	75	-0.034	0.054	1000	-1000	-0.03	-1000
BARD1 signaling events	0.0080	4	257	57	-0.041	0.089	1000	-1000	-0.046	-1000
a4b1 and a4b7 Integrin signaling	0.0080	4	20	5	0.016	0.027	1000	-1000	0.006	-1000
TRAIL signaling pathway	0.0080	4	206	48	-0.034	0.06	1000	-1000	-0.036	-1000
IL1-mediated signaling events	0.0080	4	302	62	-0.019	0.04	1000	-1000	-0.039	-1000
Signaling events mediated by HDAC Class I	0.0080	4	498	104	-0.042	0.055	1000	-1000	-0.038	-1000
FoxO family signaling	0.0080	4	265	64	-0.021	0.07	1000	-1000	-0.062	-1000
VEGFR1 specific signals	0.0080	4	250	56	-0.12	0.054	1000	-1000	-0.057	-1000
Arf6 downstream pathway	0.0060	3	136	43	-0.044	0.045	1000	-1000	-0.022	-1000
Insulin-mediated glucose transport	0.0060	3	96	32	-0.009	0.042	1000	-1000	-0.034	-1000
Class I PI3K signaling events mediated by Akt	0.0060	3	263	68	-0.033	0.047	1000	-1000	-0.036	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0060	3	127	37	-0.013	0.05	1000	-1000	-0.037	-1000
Paxillin-dependent events mediated by a4b1	0.0060	3	113	36	-0.04	0.041	1000	-1000	-0.035	-1000
E-cadherin signaling in the nascent adherens junction	0.0060	3	263	76	-0.012	0.059	1000	-1000	-0.061	-1000
Regulation of Telomerase	0.0060	3	403	102	-0.042	0.065	1000	-1000	-0.045	-1000
p38 MAPK signaling pathway	0.0060	3	143	44	-0.002	0.054	1000	-1000	-0.035	-1000
Canonical NF-kappaB pathway	0.0040	2	84	39	-0.006	0.046	1000	-1000	-0.038	-1000
Signaling mediated by p38-gamma and p38-delta	0.0040	2	30	15	-0.011	0.022	1000	-1000	-0.033	-1000
Arf6 trafficking events	0.0040	2	203	71	-0.05	0.04	1000	-1000	-0.03	-1000
Class IB PI3K non-lipid kinase events	0.0040	2	6	3	-0.019	0.019	1000	-1000	-0.009	-1000
Circadian rhythm pathway	0.0020	1	31	22	-0.006	0.047	1000	-1000	-0.043	-1000
S1P5 pathway	0.0020	1	32	17	-0.015	0.03	1000	-1000	-0.014	-1000
Rapid glucocorticoid signaling	0.0020	1	27	20	-0.01	0.024	1000	-1000	-0.017	-1000
Arf1 pathway	0.0020	1	68	54	-0.005	0.03	1000	-1000	-0.017	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	16	23	0.003	0.042	1000	-1000	-0.031	-1000
PLK2 and PLK4 events	0.0000	0	1	3	-0.01	0.022	1000	-1000	-0.027	-1000
Atypical NF-kappaB pathway	0.0000	0	11	31	-0.008	0.023	1000	-1000	-0.031	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	10	27	-0.01	0.053	1000	-1000	-0.038	-1000
E-cadherin signaling events	0.0000	0	0	5	0.021	0.041	1000	-1000	0.005	-1000
Alternative NF-kappaB pathway	0.0000	0	4	13	0	0.06	1000	-1000	0	-1000
Total	NA	2460	159831	7203	-14	9.2	131000	-131000	-5.7	-131000

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.51	0.5	-10000	0	-0.97	263	263
NCK1/PAK1/Dok-R	-0.24	0.22	-10000	0	-0.44	263	263
NCK1/Dok-R	-0.59	0.63	-10000	0	-1.1	261	261
PIK3CA	0.013	0.012	-10000	0	-10000	0	0
mol:beta2-estradiol	0.063	0.098	0.24	118	-10000	0	118
RELA	0.023	0.002	-10000	0	-10000	0	0
SHC1	0.02	0.005	-10000	0	-10000	0	0
Rac/GDP	0.016	0.003	-10000	0	-10000	0	0
F2	0.075	0.12	0.27	122	-10000	0	122
TNIP2	0.021	0.006	-10000	0	-10000	0	0
NF kappa B/RelA	-0.53	0.58	-10000	0	-1.1	261	261
FN1	0.009	0.085	-10000	0	-0.53	12	12
PLD2	-0.62	0.65	-10000	0	-1.2	259	259
PTPN11	0.023	0.002	-10000	0	-10000	0	0
GRB14	-0.01	0.13	0.23	1	-0.53	29	30
ELK1	-0.55	0.56	-10000	0	-1.1	261	261
GRB7	0.025	0.032	0.38	4	-10000	0	4
PAK1	0.023	0.016	0.38	1	-10000	0	1
Tie2/Ang1/alpha5/beta1 Integrin	-0.57	0.62	-10000	0	-1.1	261	261
CDKN1A	-0.35	0.33	-10000	0	-0.66	259	259
ITGA5	0.023	0.002	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.6	0.64	-10000	0	-1.2	261	261
CRK	0.021	0.005	-10000	0	-10000	0	0
mol:NO	-0.36	0.35	-10000	0	-0.69	263	263
PLG	-0.62	0.65	-10000	0	-1.2	260	260
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.48	0.47	-10000	0	-0.91	263	263
GRB2	0.022	0.004	-10000	0	-10000	0	0
PIK3R1	0.019	0.006	-10000	0	-10000	0	0
ANGPT2	-0.3	0.32	-10000	0	-0.71	151	151
BMX	-0.67	0.67	-10000	0	-1.3	261	261
ANGPT1	-0.35	0.56	-10000	0	-1.3	120	120
tube development	-0.4	0.37	-10000	0	-0.75	262	262
ANGPT4	-0.23	0.26	-10000	0	-0.53	211	211
response to hypoxia	-0.035	0.033	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.65	0.68	-10000	0	-1.2	261	261
alpha5/beta1 Integrin	0.033	0.007	-10000	0	-10000	0	0
FGF2	0.009	0.085	-10000	0	-0.53	12	12
STAT5A (dimer)	-0.46	0.44	-10000	0	-0.87	261	261
mol:L-citrulline	-0.36	0.35	-10000	0	-0.69	263	263
AGTR1	-0.13	0.24	-10000	0	-0.53	132	132
MAPK14	-0.67	0.67	-10000	0	-1.3	263	263
Tie2/SHP2	-0.55	0.6	-10000	0	-1.2	234	234
TEK	-0.61	0.66	-10000	0	-1.3	234	234
RPS6KB1	-0.49	0.48	-10000	0	-0.93	263	263
Angiotensin II/AT1	-0.094	0.18	-10000	0	-0.39	132	132
Tie2/Ang1/GRB2	-0.64	0.68	-10000	0	-1.2	261	261
MAPK3	-0.56	0.58	-10000	0	-1.1	258	258
MAPK1	-0.55	0.57	-10000	0	-1.1	260	260
Tie2/Ang1/GRB7	-0.64	0.68	-10000	0	-1.2	261	261
NFKB1	0.022	0.005	-10000	0	-10000	0	0
MAPK8	-0.62	0.65	-10000	0	-1.2	261	261
PI3K	-0.61	0.59	-10000	0	-1.2	263	263
FES	-0.66	0.67	-10000	0	-1.3	263	263
Crk/Dok-R	-0.6	0.64	-10000	0	-1.2	261	261
Tie2/Ang1/ABIN2	-0.64	0.69	-10000	0	-1.2	261	261
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.45	0.43	-10000	0	-0.85	263	263
STAT5A	0.022	0.003	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.48	0.47	-10000	0	-0.92	263	263
Tie2/Ang2	-0.58	0.56	-10000	0	-1.1	261	261
Tie2/Ang1	-0.68	0.74	-10000	0	-1.3	261	261
FOXO1	-0.45	0.44	-10000	0	-0.86	263	263
ELF1	-0.034	0.067	-10000	0	-10000	0	0
ELF2	-0.62	0.66	-10000	0	-1.2	261	261
mol:Choline	-0.58	0.6	-10000	0	-1.1	259	259
cell migration	-0.13	0.12	-10000	0	-0.24	263	263
FYN	-0.47	0.44	-10000	0	-0.87	261	261
DOK2	-0.021	0.14	-10000	0	-0.53	37	37
negative regulation of cell cycle	-0.32	0.3	-10000	0	-0.6	261	261
ETS1	-0.065	0.13	-10000	0	-0.28	119	119
PXN	-0.39	0.38	-10000	0	-0.75	262	262
ITGB1	0.022	0.004	-10000	0	-10000	0	0
NOS3	-0.42	0.41	-10000	0	-0.8	263	263
RAC1	0.022	0.004	-10000	0	-10000	0	0
TNF	-0.066	0.14	0.24	1	-0.28	120	121
MAPKKK cascade	-0.58	0.6	-10000	0	-1.1	259	259
RASA1	0.021	0.006	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.64	0.68	-10000	0	-1.2	260	260
NCK1	0.019	0.008	-10000	0	-10000	0	0
vasculogenesis	-0.32	0.31	-10000	0	-0.61	263	263
mol:Phosphatidic acid	-0.58	0.6	-10000	0	-1.1	259	259
mol:Angiotensin II	0	0.001	-10000	0	-10000	0	0
mol:NADP	-0.36	0.35	-10000	0	-0.69	263	263
Rac1/GTP	-0.45	0.44	-10000	0	-0.86	263	263
MMP2	-0.62	0.65	-10000	0	-1.2	259	259

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.16	0.22	-10000	0	-0.71	30	30
IHH	-0.29	0.3	-10000	0	-0.57	267	267
SHH Np/Cholesterol/GAS1	-0.027	0.11	0.19	1	-0.31	68	69
LRPAP1	0.021	0.006	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.027	0.11	0.31	68	-0.19	1	69
SMO/beta Arrestin2	-0.2	0.22	-10000	0	-0.39	252	252
SMO	-0.21	0.22	-10000	0	-0.4	265	265
AKT1	-0.11	0.15	-10000	0	-0.56	32	32
ARRB2	0.022	0.005	-10000	0	-10000	0	0
BOC	0.02	0.029	0.23	2	-0.53	1	3
ADRBK1	0.022	0.004	-10000	0	-10000	0	0
heart looping	-0.21	0.22	-10000	0	-0.4	265	265
STIL	-0.17	0.18	0.24	1	-0.46	68	69
DHH N/PTCH2	0.001	0.11	-10000	0	-0.39	38	38
DHH N/PTCH1	-0.17	0.2	-10000	0	-0.32	294	294
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
DHH	-0.022	0.14	-10000	0	-0.53	36	36
PTHLH	-0.2	0.26	-10000	0	-0.72	29	29
determination of left/right symmetry	-0.21	0.22	-10000	0	-0.4	265	265
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
skeletal system development	-0.19	0.25	-10000	0	-0.71	29	29
IHH N/Hhip	-0.41	0.27	-10000	0	-0.54	383	383
DHH N/Hhip	-0.26	0.22	-10000	0	-0.42	312	312
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.21	0.22	-10000	0	-0.4	265	265
pancreas development	-0.32	0.27	-10000	0	-0.53	302	302
HHAT	0.022	0.004	-10000	0	-10000	0	0
PI3K	0.017	0.017	-10000	0	-10000	0	0
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	0.013	0.07	-10000	0	-0.53	8	8
somite specification	-0.21	0.22	-10000	0	-0.4	265	265
SHH Np/Cholesterol/PTCH1	-0.17	0.19	-10000	0	-0.41	99	99
SHH Np/Cholesterol/PTCH2	-0.024	0.11	0.19	1	-0.31	63	64
SHH Np/Cholesterol/Megalin	-0.17	0.19	-10000	0	-0.34	263	263
SHH	-0.056	0.12	0.29	1	-0.39	60	61
catabolic process	-0.18	0.2	-10000	0	-0.34	281	281
SMO/Vitamin D3	-0.2	0.21	-10000	0	-0.43	131	131
SHH Np/Cholesterol/Hhip	-0.22	0.18	-10000	0	-0.34	310	310
LRP2	-0.25	0.28	-10000	0	-0.53	243	243
receptor-mediated endocytosis	-0.3	0.25	-10000	0	-0.56	202	202
SHH Np/Cholesterol/BOC	-0.02	0.1	-10000	0	-0.31	52	52
SHH Np/Cholesterol/CDO	-0.025	0.11	0.19	1	-0.3	65	66
mesenchymal cell differentiation	0.21	0.18	0.34	310	-10000	0	310
mol:Vitamin D3	-0.17	0.19	0.24	1	-0.44	86	87
IHH N/PTCH2	-0.18	0.2	-10000	0	-0.35	268	268
CDON	0.017	0.055	-10000	0	-0.53	5	5
IHH N/PTCH1	-0.17	0.21	-10000	0	-0.34	281	281
Megalin/LRPAP1	-0.17	0.21	-10000	0	-0.39	241	241
PTCH2	0.02	0.045	0.23	2	-0.53	3	5
SHH Np/Cholesterol	-0.03	0.1	-10000	0	-0.3	60	60
PTCH1	-0.18	0.2	-10000	0	-0.34	281	281
HHIP	-0.32	0.27	-10000	0	-0.53	302	302

×

Endothelins

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
AKT1	-0.1	0.16	-10000	0	-0.41	80	80
PTK2B	0.02	0.007	-10000	0	-10000	0	0
mol:Ca2+	-0.16	0.29	-10000	0	-0.73	74	74
EDN1	-0.093	0.17	-10000	0	-0.45	71	71
EDN3	-0.044	0.16	0.23	15	-0.53	47	62
EDN2	0.041	0.1	0.24	66	-0.53	8	74
HRAS/GDP	-0.21	0.26	-10000	0	-0.55	148	148
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.1	0.19	-10000	0	-0.43	92	92
ADCY4	-0.097	0.16	-10000	0	-0.38	93	93
ADCY5	-0.099	0.17	-10000	0	-0.4	93	93
ADCY6	-0.084	0.14	-10000	0	-0.36	75	75
ADCY7	-0.081	0.14	-10000	0	-0.36	73	73
ADCY1	-0.081	0.14	-10000	0	-0.36	72	72
ADCY2	-0.07	0.15	0.26	9	-0.38	67	76
ADCY3	-0.082	0.14	-10000	0	-0.36	75	75
ADCY8	-0.15	0.18	-10000	0	-0.35	188	188
ADCY9	-0.084	0.14	-10000	0	-0.36	75	75
arachidonic acid secretion	-0.2	0.24	-10000	0	-0.5	168	168
ETB receptor/Endothelin-1/Gq/GTP	-0.26	0.27	-10000	0	-0.43	302	302
GNAO1	0.021	0.029	0.23	2	-0.53	1	3
HRAS	0.022	0.004	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	-0.077	0.16	-10000	0	-0.38	76	76
ETA receptor/Endothelin-1/Gs/GTP	-0.075	0.15	-10000	0	-0.37	80	80
mol:GTP	-0.001	0.003	-10000	0	-10000	0	0
COL3A1	-0.1	0.15	-10000	0	-0.42	74	74
EDNRB	-0.28	0.28	-10000	0	-0.53	272	272
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.11	0.19	-10000	0	-0.48	74	74
CYSLTR1	-0.14	0.24	-10000	0	-0.58	99	99
SLC9A1	-0.054	0.095	-10000	0	-0.29	45	45
mol:GDP	-0.23	0.28	-10000	0	-0.59	151	151
SLC9A3	-0.37	0.38	-10000	0	-0.74	199	199
RAF1	-0.23	0.27	-10000	0	-0.56	166	166
JUN	-0.14	0.24	-10000	0	-0.68	55	55
JAK2	-0.099	0.16	-10000	0	-0.41	80	80
mol:IP3	-0.2	0.25	-10000	0	-0.54	151	151
ETA receptor/Endothelin-1	-0.11	0.19	-10000	0	-0.45	96	96
PLCB1	0.019	0.026	-10000	0	-0.53	1	1
PLCB2	0.01	0.07	-10000	0	-0.54	8	8
ETA receptor/Endothelin-3	-0.064	0.14	-10000	0	-0.39	59	59
FOS	-0.24	0.32	-10000	0	-0.76	110	110
Gai/GDP	-0.086	0.28	-10000	0	-0.86	53	53
CRK	0.021	0.005	-10000	0	-10000	0	0
mol:Ca ++	-0.26	0.28	-10000	0	-0.61	157	157
BCAR1	0.022	0.005	-10000	0	-10000	0	0
PRKCB1	-0.2	0.24	-10000	0	-0.51	152	152
GNAQ	0.017	0.028	-10000	0	-0.54	1	1
GNAZ	0.016	0.056	-10000	0	-0.53	5	5
GNAL	0.02	0.035	-10000	0	-0.53	2	2
Gs family/GDP	-0.2	0.24	-10000	0	-0.53	148	148
ETA receptor/Endothelin-1/Gq/GTP	-0.12	0.2	-10000	0	-0.42	125	125
MAPK14	-0.22	0.23	-10000	0	-0.49	165	165
TRPC6	-0.17	0.31	-10000	0	-0.81	70	70
GNAI2	0.021	0.007	-10000	0	-10000	0	0
GNAI3	0.022	0.005	-10000	0	-10000	0	0
GNAI1	0.021	0.025	-10000	0	-0.53	1	1
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.23	0.24	-10000	0	-0.5	175	175
ETB receptor/Endothelin-2	-0.21	0.22	0.27	1	-0.4	277	278
ETB receptor/Endothelin-3	-0.24	0.23	-10000	0	-0.42	296	296
ETB receptor/Endothelin-1	-0.27	0.23	-10000	0	-0.44	294	294
MAPK3	-0.25	0.32	-10000	0	-0.68	150	150
MAPK1	-0.25	0.33	-10000	0	-0.67	156	156
Rac1/GDP	-0.21	0.25	-10000	0	-0.55	147	147
cAMP biosynthetic process	-0.091	0.16	0.25	6	-0.43	58	64
MAPK8	-0.17	0.31	-10000	0	-0.72	87	87
SRC	0.022	0.004	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.16	0.16	-10000	0	-0.3	232	232
p130Cas/CRK/Src/PYK2	-0.22	0.28	-10000	0	-0.6	147	147
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.21	0.25	-10000	0	-0.55	144	144
COL1A2	-0.25	0.23	-10000	0	-0.58	102	102
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.014	0.11	0.27	3	-0.33	26	29
mol:DAG	-0.2	0.25	-10000	0	-0.54	151	151
MAP2K2	-0.24	0.28	-10000	0	-0.6	161	161
MAP2K1	-0.24	0.28	-10000	0	-0.6	161	161
EDNRA	-0.05	0.095	-10000	0	-0.31	35	35
positive regulation of muscle contraction	-0.085	0.14	-10000	0	-0.37	71	71
Gq family/GDP	-0.19	0.27	-10000	0	-0.56	144	144
HRAS/GTP	-0.23	0.27	-10000	0	-0.56	164	164
PRKCH	-0.2	0.24	-10000	0	-0.52	146	146
RAC1	0.022	0.004	-10000	0	-10000	0	0
PRKCA	-0.2	0.24	-10000	0	-0.53	142	142
PRKCB	-0.21	0.26	-10000	0	-0.56	147	147
PRKCE	-0.19	0.23	-10000	0	-0.52	140	140
PRKCD	-0.19	0.24	-10000	0	-0.53	138	138
PRKCG	-0.2	0.24	-10000	0	-0.53	149	149
regulation of vascular smooth muscle contraction	-0.28	0.38	-10000	0	-0.92	107	107
PRKCQ	-0.22	0.26	-10000	0	-0.56	156	156
PLA2G4A	-0.21	0.27	-10000	0	-0.54	168	168
GNA14	-0.11	0.24	-10000	0	-0.54	117	117
GNA15	0.02	0.01	-10000	0	-10000	0	0
GNA12	0.022	0.004	-10000	0	-10000	0	0
GNA11	0.02	0.01	-10000	0	-10000	0	0
Rac1/GTP	-0.077	0.16	-10000	0	-0.38	77	77
MMP1	0.1	0.1	0.41	18	-10000	0	18

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.021	0.006	-10000	0	-10000	0	0
LAT2	-0.11	0.2	-10000	0	-0.43	105	105
AP1	-0.11	0.26	-10000	0	-0.55	101	101
mol:PIP3	-0.13	0.23	0.3	11	-0.5	102	113
IKBKB	-0.06	0.14	0.22	14	-0.29	81	95
AKT1	-0.053	0.2	0.41	19	-0.42	54	73
IKBKG	-0.069	0.13	0.23	9	-0.29	82	91
MS4A2	-0.11	0.23	-10000	0	-0.53	115	115
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
MAP3K1	-0.031	0.22	0.31	32	-0.46	60	92
mol:Ca2+	-0.095	0.18	0.27	12	-0.36	102	114
LYN	0.012	0.041	-10000	0	-0.55	2	2
CBLB	-0.1	0.19	-10000	0	-0.42	99	99
SHC1	0.022	0.005	-10000	0	-10000	0	0
RasGAP/p62DOK	0.004	0.1	-10000	0	-0.31	47	47
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	0.021	0.025	-10000	0	-0.53	1	1
PLD2	-0.13	0.2	0.32	13	-0.36	184	197
PTPN13	-0.099	0.21	0.41	1	-0.53	62	63
PTPN11	0.008	0.028	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	-0.039	0.17	0.35	19	-0.34	58	77
SYK	0.015	0.018	-10000	0	-10000	0	0
GRB2	0.022	0.004	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.14	0.23	-10000	0	-0.5	111	111
LAT	-0.11	0.19	-10000	0	-0.42	106	106
PAK2	-0.038	0.24	0.25	94	-0.51	63	157
NFATC2	-0.13	0.25	-10000	0	-0.7	70	70
HRAS	-0.11	0.24	0.23	9	-0.55	86	95
GAB2	0.006	0.092	-10000	0	-0.53	14	14
PLA2G1B	-0.079	0.25	-10000	0	-0.92	38	38
Fc epsilon R1	-0.14	0.25	-10000	0	-0.44	187	187
Antigen/IgE/Fc epsilon R1	-0.12	0.23	-10000	0	-0.4	187	187
mol:GDP	-0.12	0.26	0.27	1	-0.59	89	90
JUN	0.022	0.004	-10000	0	-10000	0	0
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.021	0.007	-10000	0	-10000	0	0
FOS	-0.043	0.18	-10000	0	-0.53	58	58
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.11	0.2	-10000	0	-0.44	106	106
CHUK	-0.071	0.13	0.23	9	-0.29	81	90
KLRG1	-0.1	0.18	-10000	0	-0.46	73	73
VAV1	-0.11	0.2	-10000	0	-0.43	104	104
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.11	0.19	-10000	0	-0.42	105	105
negative regulation of mast cell degranulation	-0.087	0.18	-10000	0	-0.46	67	67
BTK	-0.14	0.28	-10000	0	-0.66	90	90
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.14	0.24	-10000	0	-0.45	137	137
GAB2/PI3K/SHP2	-0.11	0.16	-10000	0	-0.38	97	97
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.11	0.19	-10000	0	-0.36	140	140
RAF1	-0.043	0.27	-10000	0	-0.96	38	38
Fc epsilon R1/FcgammaRIIB/SHIP	-0.11	0.24	-10000	0	-0.38	187	187
FCER1G	0.002	0.092	-10000	0	-0.55	13	13
FCER1A	-0.14	0.25	-10000	0	-0.55	138	138
Antigen/IgE/Fc epsilon R1/Fyn	-0.11	0.22	-10000	0	-0.38	187	187
MAPK3	-0.042	0.25	-10000	0	-0.9	38	38
MAPK1	-0.043	0.25	-10000	0	-0.9	38	38
NFKB1	0.022	0.005	-10000	0	-10000	0	0
MAPK8	-0.05	0.24	0.38	1	-0.84	35	36
DUSP1	-0.035	0.17	-10000	0	-0.53	50	50
NF-kappa-B/RelA	-0.039	0.082	-10000	0	-0.19	60	60
actin cytoskeleton reorganization	-0.099	0.21	0.43	1	-0.54	64	65
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.091	0.19	-10000	0	-0.51	61	61
FER	-0.11	0.19	-10000	0	-0.42	105	105
RELA	0.023	0.002	-10000	0	-10000	0	0
ITK	-0.064	0.15	-10000	0	-0.43	59	59
SOS1	0.022	0.004	-10000	0	-10000	0	0
PLCG1	-0.12	0.26	0.4	3	-0.57	91	94
cytokine secretion	-0.03	0.057	-10000	0	-0.16	8	8
SPHK1	-0.1	0.19	-10000	0	-0.42	105	105
PTK2	-0.1	0.22	0.43	1	-0.57	63	64
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.14	0.24	-10000	0	-0.51	112	112
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	-0.13	0.23	0.3	11	-0.48	104	115
MAP2K2	-0.045	0.25	-10000	0	-0.9	38	38
MAP2K1	-0.046	0.25	-10000	0	-0.9	38	38
MAP2K7	0.022	0.004	-10000	0	-10000	0	0
KLRG1/SHP2	-0.084	0.18	0.22	2	-0.44	67	69
MAP2K4	-0.036	0.26	-10000	0	-0.97	34	34
Fc epsilon R1/FcgammaRIIB	-0.12	0.24	-10000	0	-0.4	188	188
mol:Choline	-0.13	0.2	0.32	13	-0.35	184	197
SHC/Grb2/SOS1	-0.078	0.2	-10000	0	-0.48	67	67
FYN	0.021	0.025	-10000	0	-0.53	1	1
DOK1	0.022	0.004	-10000	0	-10000	0	0
PXN	-0.098	0.21	0.59	1	-0.53	62	63
HCLS1	-0.1	0.19	-10000	0	-0.42	100	100
PRKCB	-0.1	0.18	0.27	8	-0.41	88	96
FCGR2B	0.015	0.061	-10000	0	-0.53	6	6
IGHE	-0.003	0.009	-10000	0	-10000	0	0
KLRG1/SHIP	-0.089	0.19	-10000	0	-0.47	67	67
LCP2	0.015	0.056	-10000	0	-0.54	5	5
PLA2G4A	-0.11	0.2	-10000	0	-0.43	106	106
RASA1	0.021	0.006	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.13	0.2	0.32	13	-0.35	184	197
IKK complex	-0.043	0.11	0.2	13	-0.23	62	75
WIPF1	0.022	0.004	-10000	0	-10000	0	0

×

Thromboxane A2 receptor signaling

Figure S5. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S5. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	-0.025	0.15	-10000	0	-0.54	41	41
GNB1/GNG2	-0.069	0.093	-10000	0	-0.19	170	170
AKT1	-0.063	0.12	-10000	0	-0.25	42	42
EGF	0.015	0.068	0.23	3	-0.53	7	10
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	-0.026	0.099	0.22	1	-0.35	30	31
mol:Ca2+	-0.1	0.16	-10000	0	-0.31	172	172
LYN	-0.013	0.069	0.26	2	-0.36	8	10
RhoA/GTP	-0.039	0.07	-10000	0	-0.14	37	37
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.11	0.18	-10000	0	-0.35	170	170
GNG2	0.016	0.056	-10000	0	-0.53	5	5
ARRB2	0.022	0.005	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.042	0.14	-10000	0	-0.58	21	21
G beta5/gamma2	-0.088	0.13	-10000	0	-0.26	166	166
PRKCH	-0.12	0.19	-10000	0	-0.37	170	170
DNM1	0.023	0.014	0.23	2	-10000	0	2
TXA2/TP beta/beta Arrestin3	0.012	0.064	-10000	0	-0.58	5	5
mol:GTP	-0.001	0.001	-10000	0	-10000	0	0
PTGDR	0.008	0.085	-10000	0	-0.53	12	12
G12 family/GTP	-0.099	0.16	-10000	0	-0.31	161	161
ADRBK1	0.022	0.004	-10000	0	-10000	0	0
ADRBK2	0.022	0.004	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0.027	0.01	-10000	0	-10000	0	0
mol:GDP	0.057	0.12	0.4	24	-10000	0	24
mol:NADP	0.017	0.05	-10000	0	-0.53	4	4
RAB11A	0.023	0.002	-10000	0	-10000	0	0
PRKG1	-0.029	0.16	-10000	0	-0.53	45	45
mol:IP3	-0.13	0.2	-10000	0	-0.39	172	172
cell morphogenesis	0.027	0.01	-10000	0	-10000	0	0
PLCB2	-0.18	0.28	-10000	0	-0.54	172	172
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.014	0.082	0.26	2	-0.33	17	19
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.013	0.07	0.26	2	-0.39	8	10
RHOA	0.021	0.007	-10000	0	-10000	0	0
PTGIR	0.011	0.078	-10000	0	-0.53	10	10
PRKCB1	-0.13	0.2	-10000	0	-0.39	175	175
GNAQ	0.021	0.025	-10000	0	-0.53	1	1
mol:L-citrulline	0.017	0.05	-10000	0	-0.53	4	4
TXA2/TXA2-R family	-0.18	0.28	-10000	0	-0.55	173	173
LCK	-0.013	0.07	0.26	2	-0.38	8	10
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.009	0.073	-10000	0	-0.32	18	18
TXA2-R family/G12 family/GDP/G beta/gamma	-0.002	0.1	-10000	0	-0.44	23	23
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.012	0.072	-10000	0	-0.32	18	18
MAPK14	-0.075	0.12	-10000	0	-0.24	159	159
TGM2/GTP	-0.15	0.24	-10000	0	-0.45	170	170
MAPK11	-0.075	0.12	-10000	0	-0.24	158	158
ARHGEF1	-0.056	0.096	-10000	0	-0.19	148	148
GNAI2	0.021	0.007	-10000	0	-10000	0	0
JNK cascade	-0.13	0.2	-10000	0	-0.4	173	173
RAB11/GDP	0.023	0.003	-10000	0	-10000	0	0
ICAM1	-0.099	0.16	-10000	0	-0.31	172	172
cAMP biosynthetic process	-0.12	0.19	-10000	0	-0.36	174	174
Gq family/GTP/EBP50	-0.036	0.096	0.24	3	-0.2	112	115
actin cytoskeleton reorganization	0.027	0.01	-10000	0	-10000	0	0
SRC	-0.012	0.065	0.26	2	-0.37	6	8
GNB5	0.022	0.003	-10000	0	-10000	0	0
GNB1	0.021	0.025	-10000	0	-0.53	1	1
EGF/EGFR	-0.007	0.092	0.2	11	-0.3	21	32
VCAM1	-0.094	0.15	-10000	0	-0.3	173	173
TP beta/Gq family/GDP/G beta5/gamma2	-0.042	0.14	-10000	0	-0.58	21	21
platelet activation	-0.1	0.16	-10000	0	-0.31	162	162
PGI2/IP	0.008	0.057	-10000	0	-0.39	10	10
PRKACA	-0.001	0.074	-10000	0	-0.35	18	18
Gq family/GDP/G beta5/gamma2	-0.041	0.14	-10000	0	-0.51	24	24
TXA2/TP beta/beta Arrestin2	0.009	0.044	-10000	0	-0.37	3	3
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.011	0.072	-10000	0	-0.34	19	19
mol:DAG	-0.14	0.23	-10000	0	-0.44	172	172
EGFR	0.023	0.081	0.36	12	-0.53	6	18
TXA2/TP alpha	-0.17	0.26	-10000	0	-0.5	174	174
Gq family/GTP	-0.057	0.12	-10000	0	-0.24	129	129
YES1	-0.013	0.065	0.22	1	-0.35	8	9
GNAI2/GTP	-0.006	0.067	-10000	0	-0.32	15	15
PGD2/DP	0.005	0.063	-10000	0	-0.35	14	14
SLC9A3R1	0.024	0.023	0.27	4	-10000	0	4
FYN	-0.013	0.07	0.26	2	-0.42	6	8
mol:NO	0.017	0.05	-10000	0	-0.53	4	4
GNA15	0.022	0.004	-10000	0	-10000	0	0
PGK/cGMP	-0.007	0.11	-10000	0	-0.35	46	46
RhoA/GDP	0.021	0.007	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.001	0.12	-10000	0	-0.47	18	18
NOS3	0.018	0.05	-10000	0	-0.53	4	4
RAC1	0.022	0.004	-10000	0	-10000	0	0
PRKCA	-0.12	0.19	-10000	0	-0.36	171	171
PRKCB	-0.12	0.2	-10000	0	-0.38	171	171
PRKCE	-0.11	0.19	-10000	0	-0.37	159	159
PRKCD	-0.13	0.2	-10000	0	-0.39	172	172
PRKCG	-0.13	0.21	-10000	0	-0.4	171	171
muscle contraction	-0.17	0.26	-10000	0	-0.5	174	174
PRKCZ	-0.11	0.18	-10000	0	-0.35	172	172
ARR3	-0.01	0.016	-10000	0	-10000	0	0
TXA2/TP beta	0.01	0.077	-10000	0	-0.33	18	18
PRKCQ	-0.13	0.2	-10000	0	-0.39	177	177
MAPKKK cascade	-0.16	0.25	-10000	0	-0.48	173	173
SELE	-0.13	0.2	-10000	0	-0.4	172	172
TP beta/GNAI2/GDP/G beta/gamma	0.021	0.083	-10000	0	-0.38	13	13
ROCK1	0.022	0.004	-10000	0	-10000	0	0
GNA14	-0.11	0.24	-10000	0	-0.53	117	117
chemotaxis	-0.21	0.31	-10000	0	-0.62	172	172
GNA12	0.022	0.004	-10000	0	-10000	0	0
GNA13	0.022	0.003	-10000	0	-10000	0	0
GNA11	0.022	0.004	-10000	0	-10000	0	0
Rac1/GTP	0.016	0.003	-10000	0	-10000	0	0

×

amb2 Integrin 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.011	0.16	-10000	0	-0.49	41	41
alphaM/beta2 Integrin/GPIbA	-0.012	0.16	-10000	0	-0.48	43	43
alphaM/beta2 Integrin/proMMP-9	-0.002	0.15	0.23	1	-0.47	40	41
PLAUR	0.022	0.004	-10000	0	-10000	0	0
HMGB1	0.014	0.021	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.01	0.15	-10000	0	-0.46	41	41
AGER	-0.48	0.18	-10000	0	-0.54	443	443
RAP1A	0.022	0.005	-10000	0	-10000	0	0
SELPLG	-0.014	0.14	-10000	0	-0.53	33	33
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.33	0.2	-10000	0	-0.37	440	440
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	0.034	0.049	0.24	27	-10000	0	27
CYR61	-0.003	0.12	-10000	0	-0.53	23	23
TLN1	0.021	0.007	-10000	0	-10000	0	0
Rap1/GTP	-0.14	0.26	-10000	0	-0.5	119	119
RHOA	0.021	0.007	-10000	0	-10000	0	0
P-selectin oligomer	-0.11	0.23	-10000	0	-0.53	115	115
MYH2	-0.22	0.28	-10000	0	-0.6	147	147
MST1R	-0.007	0.12	-10000	0	-0.53	25	25
leukocyte activation during inflammatory response	-0.015	0.15	-10000	0	-0.4	59	59
APOB	-0.011	0.13	0.23	4	-0.53	27	31
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	0.017	0.05	-10000	0	-0.53	4	4
JAM3	0.021	0.025	-10000	0	-0.53	1	1
GP1BA	0.016	0.051	0.23	1	-0.53	4	5
alphaM/beta2 Integrin/CTGF	-0.021	0.18	-10000	0	-0.52	48	48
alphaM/beta2 Integrin	-0.18	0.3	-10000	0	-0.58	123	123
JAM3 homodimer	0.021	0.025	-10000	0	-0.53	1	1
ICAM2	-0.014	0.14	-10000	0	-0.53	33	33
ICAM1	-0.017	0.14	-10000	0	-0.53	35	35
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.17	0.3	-10000	0	-0.57	123	123
cell adhesion	-0.013	0.15	-10000	0	-0.48	43	43
NFKB1	-0.34	0.23	-10000	0	-0.7	109	109
THY1	0.022	0.004	-10000	0	-10000	0	0
RhoA/GDP	0.015	0.005	-10000	0	-10000	0	0
Lipoprotein(a)	0.013	0.087	0.24	1	-0.34	26	27
alphaM/beta2 Integrin/LRP/tPA	0.002	0.14	0.26	4	-0.44	40	44
IL6	-0.36	0.31	-10000	0	-0.91	105	105
ITGB2	-0.006	0.11	-10000	0	-0.54	18	18
elevation of cytosolic calcium ion concentration	0.008	0.15	0.25	1	-0.45	39	40
alphaM/beta2 Integrin/JAM2/JAM3	-0.047	0.2	-10000	0	-0.44	90	90
JAM2	-0.061	0.2	-10000	0	-0.53	74	74
alphaM/beta2 Integrin/ICAM1	-0.02	0.2	-10000	0	-0.44	78	78
alphaM/beta2 Integrin/uPA/Plg	0.008	0.15	0.26	1	-0.45	40	41
RhoA/GTP	-0.21	0.3	-10000	0	-0.63	130	130
positive regulation of phagocytosis	-0.12	0.23	-10000	0	-0.5	98	98
Ron/MSP	0.008	0.094	-10000	0	-0.39	25	25
alphaM/beta2 Integrin/uPAR/uPA	0.009	0.15	0.26	1	-0.45	39	40
alphaM/beta2 Integrin/uPAR	-0.009	0.15	-10000	0	-0.48	40	40
PLAU	0.035	0.053	0.24	32	-10000	0	32
PLAT	0.024	0.035	0.33	6	-10000	0	6
actin filament polymerization	-0.22	0.26	-10000	0	-0.56	149	149
MST1	0.021	0.011	0.23	1	-10000	0	1
alphaM/beta2 Integrin/lipoprotein(a)	-0.012	0.16	-10000	0	-0.4	59	59
TNF	-0.32	0.22	-10000	0	-0.68	106	106
RAP1B	0.022	0.005	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.002	0.16	0.26	1	-0.48	40	41
fibrinolysis	0.007	0.15	0.25	1	-0.44	40	41
HCK	0.018	0.043	-10000	0	-0.53	3	3
dendritic cell antigen processing and presentation	-0.17	0.3	-10000	0	-0.57	123	123
VTN	-0.18	0.27	0.23	2	-0.53	185	187
alphaM/beta2 Integrin/CYR61	-0.025	0.18	-10000	0	-0.51	52	52
LPA	0.02	0.046	0.24	18	-10000	0	18
LRP1	0.023	0.002	-10000	0	-10000	0	0
cell migration	-0.013	0.14	-10000	0	-0.46	40	40
FN1	0.009	0.085	-10000	0	-0.53	12	12
alphaM/beta2 Integrin/Thy1	-0.01	0.15	-10000	0	-0.48	40	40
MPO	-0.003	0.11	-10000	0	-0.53	22	22
KNG1	0.007	0.053	0.31	13	-10000	0	13
RAP1/GDP	0.028	0.009	-10000	0	-10000	0	0
ROCK1	-0.19	0.28	-10000	0	-0.6	121	121
ELA2	0	0	-10000	0	-10000	0	0
PLG	-0.004	0.03	0.23	5	-10000	0	5
CTGF	0.003	0.1	-10000	0	-0.53	18	18
alphaM/beta2 Integrin/Hck	-0.01	0.14	-10000	0	-0.46	40	40
ITGAM	-0.03	0.15	-10000	0	-0.54	40	40
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.089	0.25	-10000	0	-0.46	129	129
HP	-0.13	0.25	-10000	0	-0.53	137	137
leukocyte adhesion	-0.32	0.23	-10000	0	-0.58	155	155
SELP	-0.11	0.23	-10000	0	-0.53	115	115

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.44	0.53	-10000	0	-1.3	106	106
STAT6 (cleaved dimer)	-0.45	0.54	-10000	0	-1.3	116	116
IGHG1	-0.14	0.18	-10000	0	-0.74	3	3
IGHG3	-0.43	0.51	-10000	0	-1.2	114	114
AKT1	-0.21	0.3	-10000	0	-0.95	36	36
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.15	0.26	-10000	0	-1	22	22
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.22	0.32	-10000	0	-1.1	33	33
THY1	-0.45	0.53	-10000	0	-1.3	107	107
MYB	0.026	0.05	0.23	15	-0.53	2	17
HMGA1	0.024	0.019	0.23	4	-10000	0	4
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.25	0.32	-10000	0	-0.83	51	51
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.22	0.32	-10000	0	-1.1	34	34
SP1	0.026	0.003	-10000	0	-10000	0	0
INPP5D	0.021	0.025	-10000	0	-0.53	1	1
SOCS5	0.02	0.03	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.44	0.54	-10000	0	-1.2	116	116
SOCS1	-0.29	0.34	-10000	0	-0.76	101	101
SOCS3	-0.21	0.27	-10000	0	-0.93	20	20
FCER2	-0.41	0.51	-10000	0	-1.3	87	87
PARP14	0.02	0.009	-10000	0	-10000	0	0
CCL17	-0.51	0.6	-10000	0	-1.4	128	128
GRB2	0.022	0.004	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.18	0.26	-10000	0	-0.86	32	32
T cell proliferation	-0.44	0.54	-10000	0	-1.3	113	113
IL4R/JAK1	-0.44	0.54	-10000	0	-1.2	112	112
EGR2	-0.46	0.56	-10000	0	-1.3	118	118
JAK2	-0.019	0.047	-10000	0	-10000	0	0
JAK3	0.026	0.009	-10000	0	-10000	0	0
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
JAK1	0	0.026	-10000	0	-10000	0	0
COL1A2	-0.11	0.16	-10000	0	-10000	0	0
CCL26	-0.44	0.53	-10000	0	-1.2	111	111
IL4R	-0.47	0.57	-10000	0	-1.3	111	111
PTPN6	0.026	0.022	-10000	0	-10000	0	0
IL13RA2	-0.47	0.56	-10000	0	-1.3	117	117
IL13RA1	-0.019	0.05	-10000	0	-10000	0	0
IRF4	-0.2	0.37	-10000	0	-0.89	92	92
ARG1	-0.13	0.22	-10000	0	-0.77	30	30
CBL	-0.24	0.3	-10000	0	-0.79	48	48
GTF3A	0.028	0.01	-10000	0	-10000	0	0
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.019	0.067	-10000	0	-10000	0	0
IRF4/BCL6	-0.16	0.32	-10000	0	-0.77	87	87
CD40LG	-0.068	0.21	-10000	0	-0.53	83	83
MAPK14	-0.23	0.31	-10000	0	-0.86	38	38
mitosis	-0.2	0.28	-10000	0	-0.87	36	36
STAT6	-0.52	0.67	-10000	0	-1.5	114	114
SPI1	-0.014	0.14	-10000	0	-0.53	35	35
RPS6KB1	-0.2	0.27	-10000	0	-0.85	33	33
STAT6 (dimer)	-0.52	0.67	-10000	0	-1.5	114	114
STAT6 (dimer)/PARP14	-0.47	0.59	-10000	0	-1.4	110	110
mast cell activation	0.01	0.013	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.23	0.33	-10000	0	-0.96	47	47
FRAP1	-0.21	0.3	-10000	0	-0.94	36	36
LTA	-0.44	0.53	-10000	0	-1.3	110	110
FES	0.021	0.025	-10000	0	-0.53	1	1
T-helper 1 cell differentiation	0.5	0.62	1.4	114	-10000	0	114
CCL11	-0.44	0.52	-10000	0	-1.2	115	115
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.2	0.29	-10000	0	-1	27	27
IL2RG	0.019	0.066	-10000	0	-0.52	7	7
IL10	-0.45	0.53	-10000	0	-1.2	112	112
IRS1	0.022	0.004	-10000	0	-10000	0	0
IRS2	0.018	0.043	-10000	0	-0.53	3	3
IL4	-0.14	0.27	-10000	0	-1.1	29	29
IL5	-0.45	0.53	-10000	0	-1.3	108	108
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.37	0.46	-10000	0	-1	111	111
COL1A1	-0.15	0.25	-10000	0	-1	20	20
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.46	0.56	-10000	0	-1.3	105	105
IL2R gamma/JAK3	0.03	0.051	-10000	0	-0.38	7	7
TFF3	-0.49	0.6	-10000	0	-1.4	112	112
ALOX15	-0.66	0.73	-10000	0	-1.5	192	192
MYBL1	0.022	0.01	0.23	1	-10000	0	1
T-helper 2 cell differentiation	-0.49	0.51	-10000	0	-1.1	155	155
SHC1	0.022	0.005	-10000	0	-10000	0	0
CEBPB	0.025	0.006	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.21	0.31	-10000	0	-1.1	28	28
mol:PI-3-4-5-P3	-0.21	0.3	-10000	0	-0.94	36	36
PI3K	-0.23	0.32	-10000	0	-1.1	35	35
DOK2	-0.021	0.14	-10000	0	-0.53	37	37
ETS1	0.01	0.078	-10000	0	-0.5	10	10
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.16	0.23	-10000	0	-0.74	29	29
ITGB3	-0.46	0.55	-10000	0	-1.3	114	114
PIGR	-0.81	0.78	-10000	0	-1.5	263	263
IGHE	0.046	0.053	0.2	13	-10000	0	13
MAPKKK cascade	-0.15	0.22	-10000	0	-0.72	29	29
BCL6	0.014	0.011	-10000	0	-10000	0	0
OPRM1	-0.45	0.53	-10000	0	-1.3	110	110
RETNLB	-0.43	0.54	-10000	0	-1.2	110	110
SELP	-0.6	0.71	-10000	0	-1.5	158	158
AICDA	-0.42	0.51	-10000	0	-1.2	108	108

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.1	0.34	-10000	0	-1.1	51	51
MKNK1	0.022	0.004	-10000	0	-10000	0	0
MAPK14	-0.014	0.12	-10000	0	-0.32	68	68
ATF2/c-Jun	-0.021	0.096	-10000	0	-0.4	5	5
MAPK11	-0.016	0.12	-10000	0	-0.32	71	71
MITF	-0.04	0.15	-10000	0	-0.37	79	79
MAPKAPK5	-0.031	0.14	-10000	0	-0.37	74	74
KRT8	-0.03	0.14	-10000	0	-0.37	73	73
MAPKAPK3	0.021	0.007	-10000	0	-10000	0	0
MAPKAPK2	0.022	0.004	-10000	0	-10000	0	0
p38alpha-beta/CK2	-0.029	0.18	-10000	0	-0.47	68	68
CEBPB	-0.03	0.14	-10000	0	-0.36	73	73
SLC9A1	-0.033	0.14	-10000	0	-0.38	73	73
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	-0.027	0.14	-10000	0	-0.36	68	68
p38alpha-beta/MNK1	-0.008	0.16	-10000	0	-0.38	67	67
JUN	-0.02	0.096	-10000	0	-0.4	5	5
PPARGC1A	-0.1	0.23	-10000	0	-0.43	140	140
USF1	-0.029	0.14	-10000	0	-0.36	71	71
RAB5/GDP/GDI1	-0.017	0.11	-10000	0	-0.28	61	61
NOS2	-0.064	0.27	-10000	0	-1.1	29	29
DDIT3	-0.03	0.14	-10000	0	-0.36	73	73
RAB5A	0.021	0.006	-10000	0	-10000	0	0
HSPB1	-0.028	0.12	0.27	8	-0.31	66	74
p38alpha-beta/HBP1	-0.008	0.16	-10000	0	-0.39	65	65
CREB1	-0.033	0.15	-10000	0	-0.39	71	71
RAB5/GDP	0.016	0.005	-10000	0	-10000	0	0
EIF4E	-0.032	0.13	-10000	0	-0.35	62	62
RPS6KA4	-0.031	0.14	-10000	0	-0.37	73	73
PLA2G4A	-0.033	0.13	0.26	1	-0.35	63	64
GDI1	-0.028	0.14	-10000	0	-0.37	69	69
TP53	-0.052	0.17	-10000	0	-0.47	72	72
RPS6KA5	-0.031	0.14	-10000	0	-0.37	72	72
ESR1	-0.05	0.18	-10000	0	-0.41	86	86
HBP1	0.022	0.005	-10000	0	-10000	0	0
MEF2C	-0.041	0.16	-10000	0	-0.39	78	78
MEF2A	-0.03	0.14	-10000	0	-0.37	72	72
EIF4EBP1	-0.03	0.15	-10000	0	-0.39	68	68
KRT19	-0.036	0.16	-10000	0	-0.39	76	76
ELK4	-0.03	0.14	-10000	0	-0.36	73	73
ATF6	-0.029	0.14	-10000	0	-0.36	71	71
ATF1	-0.032	0.15	-10000	0	-0.38	71	71
p38alpha-beta/MAPKAPK2	-0.008	0.16	-10000	0	-0.38	68	68
p38alpha-beta/MAPKAPK3	-0.011	0.16	-10000	0	-0.38	68	68

×

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	0.016	0.036	-10000	0	-0.5	2	2
CDKN2C	0.024	0.02	-10000	0	-10000	0	0
CDKN2A	0.092	0.14	0.23	207	-0.29	20	227
CCND2	-0.008	0.054	0.23	5	-0.38	7	12
RB1	-0.009	0.083	0.43	6	-0.24	39	45
CDK4	-0.001	0.07	0.25	20	-0.43	6	26
CDK6	-0.002	0.071	0.25	20	-0.44	6	26
G1/S progression	0.036	0.1	0.21	110	-0.42	6	116

×

Aurora B signaling

Figure S10. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S10. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.056	0.088	0.27	18	-0.33	8	26
STMN1	-0.045	0.045	-10000	0	-0.26	1	1
Aurora B/RasGAP/Survivin	0.22	0.14	0.32	297	-0.21	7	304
Chromosomal passenger complex/Cul3 protein complex	0.036	0.079	0.2	8	-0.32	12	20
BIRC5	0.21	0.084	0.24	422	-0.32	1	423
DES	-0.3	0.31	-10000	0	-0.66	91	91
Aurora C/Aurora B/INCENP	0.12	0.088	0.29	1	-0.33	1	2
Aurora B/TACC1	0.091	0.091	-10000	0	-0.18	17	17
Aurora B/PP2A	0.12	0.097	-10000	0	-0.2	21	21
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	0.017	0.03	0.13	4	-0.12	1	5
mitotic metaphase/anaphase transition	-0.003	0.005	-10000	0	-10000	0	0
NDC80	-0.049	0.1	0.34	22	-0.24	18	40
Cul3 protein complex	0.039	0.029	0.25	1	-10000	0	1
KIF2C	0.066	0.083	0.16	19	-0.38	11	30
PEBP1	0.021	0.006	-10000	0	-10000	0	0
KIF20A	0.11	0.13	0.23	242	-0.3	15	257
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.12	0.096	-10000	0	-0.21	6	6
SEPT1	0.023	0.01	0.23	1	-10000	0	1
SMC2	0.022	0.004	-10000	0	-10000	0	0
SMC4	0.016	0.011	-10000	0	-10000	0	0
NSUN2/NPM1/Nucleolin	0.07	0.18	-10000	0	-0.58	30	30
PSMA3	0.022	0.004	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.005	0.003	-10000	0	-10000	0	0
H3F3B	0.042	0.061	0.17	8	-0.22	19	27
AURKB	0.16	0.14	0.24	335	-0.3	21	356
AURKC	0.021	0.027	0.23	1	-0.53	1	2
CDCA8	0.079	0.098	0.24	128	-0.32	1	129
cytokinesis	0.044	0.11	0.26	2	-0.4	22	24
Aurora B/Septin1	0.12	0.14	0.3	15	-0.4	17	32
AURKA	0.029	0.049	0.24	24	-10000	0	24
INCENP	0.024	0.009	-10000	0	-10000	0	0
KLHL13	0.028	0.038	0.27	11	-10000	0	11
BUB1	0.042	0.066	0.24	47	-10000	0	47
hSgo1/Aurora B/Survivin	0.26	0.19	0.38	326	-0.25	30	356
EVI5	0.026	0.006	-10000	0	-10000	0	0
RhoA/GTP	0.096	0.094	0.25	29	-0.29	5	34
SGOL1	0.11	0.13	0.23	238	-0.3	21	259
CENPA	0.075	0.078	0.23	11	-0.24	10	21
NCAPG	0.057	0.091	0.23	92	-0.3	5	97
Aurora B/HC8 Proteasome	0.12	0.097	-10000	0	-0.21	17	17
NCAPD2	0.022	0.017	0.38	1	-10000	0	1
Aurora B/PP1-gamma	0.12	0.097	-10000	0	-0.21	21	21
RHOA	0.021	0.007	-10000	0	-10000	0	0
NCAPH	0.13	0.11	0.24	255	-10000	0	255
NPM1	0.016	0.18	-10000	0	-0.72	24	24
RASA1	0.021	0.006	-10000	0	-10000	0	0
KLHL9	0.019	0.009	-10000	0	-10000	0	0
mitotic prometaphase	-0.002	0.002	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.12	0.097	-10000	0	-0.2	17	17
PPP1CC	0.023	0.002	-10000	0	-10000	0	0
Centraspindlin	0.1	0.1	0.26	69	-0.31	8	77
RhoA/GDP	0.015	0.005	-10000	0	-10000	0	0
NSUN2	0.06	0.11	-10000	0	-0.36	24	24
MYLK	0.047	0.07	0.16	40	-0.23	19	59
KIF23	0.066	0.085	0.24	97	-10000	0	97
VIM	-0.05	0.075	0.28	3	-0.3	22	25
RACGAP1	0.025	0.008	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
NCL	0.034	0.14	-10000	0	-0.5	22	22
Chromosomal passenger complex	0.06	0.08	0.19	15	-0.28	15	30
Chromosomal passenger complex/EVI5	0.28	0.17	0.38	319	-0.25	6	325
TACC1	0.018	0.026	-10000	0	-0.53	1	1
PPP2R5D	0.022	0.004	-10000	0	-10000	0	0
CUL3	0.022	0.005	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.018	0.063	0.36	7	-10000	0	7
VDR	0.021	0.025	-10000	0	-0.53	1	1
FAM120B	0.022	0.004	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.11	0.14	-10000	0	-0.41	20	20
RXRs/LXRs/DNA/Oxysterols	-0.096	0.14	-10000	0	-0.56	11	11
MED1	0.022	0.004	-10000	0	-10000	0	0
mol:9cRA	0.001	0.007	-10000	0	-10000	0	0
RARs/THRs/DNA/Src-1	-0.001	0.07	-10000	0	-0.26	17	17
RXRs/NUR77	-0.16	0.21	-10000	0	-0.35	265	265
RXRs/PPAR	-0.14	0.16	-10000	0	-0.29	259	259
NCOR2	0.021	0.025	-10000	0	-0.53	1	1
VDR/VDR/Vit D3	0.016	0.018	-10000	0	-0.39	1	1
RARs/VDR/DNA/Vit D3	0.046	0.029	-10000	0	-0.28	2	2
RARA	0.022	0.004	-10000	0	-10000	0	0
NCOA1	0.022	0.003	-10000	0	-10000	0	0
VDR/VDR/DNA	0.021	0.025	-10000	0	-0.53	1	1
RARs/RARs/DNA/9cRA	0.036	0.022	-10000	0	-0.27	1	1
RARG	0.023	0.002	-10000	0	-10000	0	0
RPS6KB1	0.037	0.081	0.65	7	-10000	0	7
RARs/THRs/DNA/SMRT	0	0.072	-10000	0	-0.27	20	20
THRA	0.022	0.004	-10000	0	-10000	0	0
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.016	0.018	-10000	0	-0.39	1	1
RXRs/PPAR/9cRA/PGJ2/DNA	-0.12	0.17	-10000	0	-0.3	241	241
NR1H4	-0.001	0.029	0.23	4	-10000	0	4
RXRs/LXRs/DNA	-0.11	0.18	-10000	0	-0.29	235	235
NR1H2	0.023	0.012	-10000	0	-10000	0	0
NR1H3	0.023	0.011	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.12	0.17	-10000	0	-0.29	238	238
NR4A1	-0.05	0.19	-10000	0	-0.53	65	65
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.1	0.12	-10000	0	-0.22	239	239
RXRG	-0.25	0.28	-10000	0	-0.53	244	244
RXR alpha/CCPG	0.033	0.012	-10000	0	-10000	0	0
RXRA	0.023	0.011	-10000	0	-10000	0	0
RXRB	0.023	0.011	-10000	0	-10000	0	0
THRB	0.002	0.1	-10000	0	-0.53	17	17
PPARG	-0.036	0.17	-10000	0	-0.53	51	51
PPARD	0.022	0.003	-10000	0	-10000	0	0
TNF	-0.1	0.19	-10000	0	-1.1	12	12
mol:Oxysterols	0.002	0.006	-10000	0	-10000	0	0
cholesterol transport	-0.095	0.13	-10000	0	-0.55	11	11
PPARA	0.022	0.005	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.019	0.036	-10000	0	-0.53	2	2
RXRs/NUR77/BCL2	-0.15	0.17	-10000	0	-0.3	265	265
SREBF1	-0.087	0.13	-10000	0	-0.55	9	9
RXRs/RXRs/DNA/9cRA	-0.12	0.17	-10000	0	-0.3	241	241
ABCA1	-0.088	0.13	-10000	0	-0.57	7	7
RARs/THRs	0.048	0.068	-10000	0	-0.29	17	17
RXRs/FXR	-0.12	0.18	-10000	0	-0.31	241	241
BCL2	0.023	0.016	0.38	1	-10000	0	1

×

Aurora C 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
INCENP	0.023	0.002	-10000	0	-10000	0	0
Aurora C/Aurora B/INCENP	0.11	0.085	0.29	1	-0.34	1	2
metaphase	0	0	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
H3F3B	-0.004	0.022	-10000	0	-0.42	1	1
AURKB	0.15	0.13	0.23	335	-0.3	21	356
AURKC	0.021	0.027	0.23	1	-0.53	1	2

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.021	0.089	-10000	0	-0.42	16	16
Crk/p130 Cas/Paxillin	-0.05	0.11	-10000	0	-0.29	53	53
JUN	-0.019	0.11	0.26	7	-0.33	6	13
HRAS	0.022	0.004	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.001	0.16	0.28	21	-0.32	77	98
RAP1A	0.022	0.005	-10000	0	-10000	0	0
FRS2	0.022	0.005	-10000	0	-10000	0	0
RAP1A/GDP	0.016	0.003	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.003	0.16	0.35	4	-0.32	82	86
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.023	0.002	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.021	0.005	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.019	0.15	0.24	18	-0.31	89	107
RHOA	0.021	0.007	-10000	0	-10000	0	0
RAP1A/GTP	-0.007	0.14	0.32	3	-0.28	83	86
GRB7	0.025	0.032	0.38	4	-10000	0	4
RET51/GFRalpha1/GDNF	-0.004	0.16	0.27	20	-0.32	81	101
MAPKKK cascade	-0.025	0.13	0.27	2	-0.3	69	71
BCAR1	0.022	0.005	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.018	0.15	0.24	19	-0.31	89	108
lamellipodium assembly	-0.037	0.11	-10000	0	-0.27	56	56
RET51/GFRalpha1/GDNF/SHC	-0.005	0.16	0.27	19	-0.32	80	99
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.019	0.15	0.24	17	-0.31	84	101
RET9/GFRalpha1/GDNF/Shank3	-0.02	0.15	0.24	17	-0.31	88	105
MAPK3	-0.041	0.13	0.27	2	-0.28	79	81
DOK1	0.022	0.004	-10000	0	-10000	0	0
DOK6	-0.024	0.15	-10000	0	-0.53	41	41
PXN	0.023	0.002	-10000	0	-10000	0	0
neurite development	-0.046	0.13	0.32	1	-0.36	14	15
DOK5	0.021	0.038	0.23	2	-0.53	2	4
GFRA1	-0.11	0.23	-10000	0	-0.53	115	115
MAPK8	-0.032	0.11	0.28	7	-0.34	7	14
HRAS/GTP	-0.016	0.15	0.35	2	-0.32	74	76
tube development	-0.018	0.15	0.24	18	-0.3	88	106
MAPK1	-0.04	0.12	0.25	3	-0.28	73	76
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.032	0.11	-10000	0	-0.25	86	86
Rac1/GDP	0.016	0.003	-10000	0	-10000	0	0
SRC	0.022	0.004	-10000	0	-10000	0	0
PDLIM7	0.021	0.006	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.019	0.18	0.35	4	-0.34	104	108
SHC1	0.022	0.005	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.005	0.16	0.27	20	-0.32	83	103
RET51/GFRalpha1/GDNF/Dok5	-0.006	0.16	0.28	19	-0.32	83	102
PRKCA	0.02	0.035	-10000	0	-0.53	2	2
HRAS/GDP	0.016	0.003	-10000	0	-10000	0	0
CREB1	-0.037	0.13	0.27	3	-0.28	80	83
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.034	0.12	0.17	15	-0.26	86	101
RET51/GFRalpha1/GDNF/Grb7	-0.003	0.16	0.28	24	-0.31	83	107
mol:GDP	0	0	-10000	0	-10000	0	0
RET	0.029	0.04	0.24	17	-10000	0	17
DOK4	0.022	0.005	-10000	0	-10000	0	0
JNK cascade	-0.018	0.11	0.26	7	-0.33	6	13
RET9/GFRalpha1/GDNF/FRS2	-0.017	0.15	0.24	18	-0.31	85	103
SHANK3	0.021	0.025	-10000	0	-0.53	1	1
RASA1	0.021	0.006	-10000	0	-10000	0	0
NCK1	0.019	0.008	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.033	0.11	-10000	0	-0.26	82	82
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.028	0.12	0.26	2	-0.25	76	78
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.031	0.12	0.28	2	-0.28	29	31
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.026	0.11	0.28	2	-0.25	76	78
PI3K	-0.037	0.17	0.28	9	-0.39	59	68
SOS1	0.022	0.004	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.012	0.15	0.24	17	-0.3	88	105
GRB10	0.022	0.005	-10000	0	-10000	0	0
activation of MAPKK activity	-0.027	0.11	0.2	18	-0.28	1	19
RET51/GFRalpha1/GDNF/FRS2	-0.004	0.16	0.28	20	-0.32	82	102
GAB1	0.021	0.006	-10000	0	-10000	0	0
IRS1	0.022	0.004	-10000	0	-10000	0	0
IRS2	0.018	0.043	-10000	0	-0.53	3	3
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.03	0.12	-10000	0	-0.26	82	82
RET51/GFRalpha1/GDNF/PKC alpha	-0.006	0.16	0.28	21	-0.32	86	107
GRB2	0.022	0.004	-10000	0	-10000	0	0
PRKACA	0.022	0.004	-10000	0	-10000	0	0
GDNF	0.054	0.1	0.28	80	-10000	0	80
RAC1	0.022	0.004	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.005	0.16	0.28	21	-0.32	85	106
Rac1/GTP	-0.032	0.14	0.21	6	-0.32	55	61
RET9/GFRalpha1/GDNF	-0.031	0.16	0.24	19	-0.34	90	109
GFRalpha1/GDNF	-0.039	0.18	0.27	19	-0.38	95	114

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	-0.026	0.14	0.33	3	-0.39	53	56
CRKL	-0.038	0.14	-10000	0	-0.41	54	54
HRAS	-0.033	0.15	-10000	0	-0.4	51	51
mol:PIP3	-0.006	0.14	0.25	1	-0.35	53	54
SPRED1	0.022	0.003	-10000	0	-10000	0	0
SPRED2	0.021	0.005	-10000	0	-10000	0	0
GAB1	-0.04	0.15	-10000	0	-0.42	63	63
FOXO3	-0.026	0.14	-10000	0	-0.37	58	58
AKT1	-0.027	0.15	-10000	0	-0.39	66	66
BAD	-0.026	0.14	0.27	1	-0.37	58	59
megakaryocyte differentiation	-0.056	0.17	-10000	0	-0.44	67	67
GSK3B	-0.008	0.15	0.29	7	-0.37	54	61
RAF1	-0.024	0.12	-10000	0	-0.33	49	49
SHC1	0.022	0.005	-10000	0	-10000	0	0
STAT3	-0.042	0.15	-10000	0	-0.42	63	63
STAT1	-0.12	0.36	-10000	0	-1	63	63
HRAS/SPRED1	-0.014	0.13	-10000	0	-0.38	26	26
cell proliferation	-0.04	0.15	-10000	0	-0.41	64	64
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
TEC	0.019	0.036	-10000	0	-0.53	2	2
RPS6KB1	-0.033	0.15	-10000	0	-0.41	63	63
HRAS/SPRED2	-0.015	0.13	-10000	0	-0.35	37	37
LYN/TEC/p62DOK	-0.013	0.15	-10000	0	-0.42	53	53
MAPK3	-0.018	0.098	0.36	2	-0.3	18	20
STAP1	-0.052	0.17	-10000	0	-0.47	63	63
GRAP2	-0.008	0.13	-10000	0	-0.53	27	27
JAK2	-0.095	0.32	-10000	0	-0.9	63	63
STAT1 (dimer)	-0.11	0.34	-10000	0	-1	63	63
mol:Gleevec	0.001	0.006	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.014	0.16	-10000	0	-0.41	60	60
actin filament polymerization	-0.041	0.14	-10000	0	-0.42	59	59
LYN	0.02	0.035	-10000	0	-0.53	2	2
STAP1/STAT5A (dimer)	-0.078	0.24	-10000	0	-0.66	63	63
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.014	0.14	-10000	0	-0.38	53	53
PI3K	-0.021	0.12	-10000	0	-0.4	32	32
PTEN	0.02	0.007	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.12	0.42	-10000	0	-1.2	63	63
MAPK8	-0.041	0.15	-10000	0	-0.42	64	64
STAT3 (dimer)	-0.041	0.14	-10000	0	-0.41	63	63
positive regulation of transcription	-0.013	0.082	0.34	2	-0.24	18	20
mol:GDP	-0.032	0.15	-10000	0	-0.41	54	54
PIK3C2B	-0.041	0.15	-10000	0	-0.42	61	61
CBL/CRKL	-0.024	0.14	-10000	0	-0.39	55	55
FER	-0.04	0.15	-10000	0	-0.42	63	63
SH2B3	-0.043	0.15	-10000	0	-0.42	64	64
PDPK1	-0.003	0.13	-10000	0	-0.33	48	48
SNAI2	-0.042	0.15	-10000	0	-0.42	62	62
positive regulation of cell proliferation	-0.083	0.27	-10000	0	-0.75	64	64
KITLG	0.017	0.022	-10000	0	-10000	0	0
cell motility	-0.083	0.27	-10000	0	-0.75	64	64
PTPN6	0.022	0.011	-10000	0	-10000	0	0
EPOR	-0.033	0.19	-10000	0	-0.88	14	14
STAT5A (dimer)	-0.066	0.22	-10000	0	-0.62	64	64
SOCS1	0.021	0.025	-10000	0	-0.53	1	1
cell migration	0.051	0.16	0.43	67	-10000	0	67
SOS1	0.022	0.004	-10000	0	-10000	0	0
EPO	0.018	0.029	0.23	6	-10000	0	6
VAV1	0.019	0.043	-10000	0	-0.53	3	3
GRB10	-0.04	0.14	-10000	0	-0.42	59	59
PTPN11	0.023	0.007	-10000	0	-10000	0	0
SCF/KIT	-0.041	0.16	-10000	0	-0.44	64	64
GO:0007205	0.002	0.008	-10000	0	-10000	0	0
MAP2K1	-0.019	0.1	0.38	2	-0.32	18	20
CBL	0.022	0.004	-10000	0	-10000	0	0
KIT	-0.16	0.46	-10000	0	-1.3	70	70
MAP2K2	-0.019	0.1	0.38	2	-0.31	19	21
SHC/Grb2/SOS1	-0.011	0.15	-10000	0	-0.4	55	55
STAT5A	-0.066	0.23	-10000	0	-0.65	63	63
GRB2	0.022	0.004	-10000	0	-10000	0	0
response to radiation	-0.041	0.14	-10000	0	-0.41	62	62
SHC/GRAP2	0.008	0.096	-10000	0	-0.39	27	27
PTPRO	-0.057	0.17	-10000	0	-0.46	67	67
SH2B2	-0.042	0.15	-10000	0	-0.42	59	59
DOK1	0.022	0.004	-10000	0	-10000	0	0
MATK	-0.052	0.16	-10000	0	-0.44	66	66
CREBBP	0.017	0.045	-10000	0	-10000	0	0
BCL2	-0.042	0.22	-10000	0	-0.98	17	17

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.005	0.002	-10000	0	-10000	0	0
GNB1/GNG2	-0.032	0.14	-10000	0	-0.3	101	101
regulation of S phase of mitotic cell cycle	-0.032	0.09	-10000	0	-0.26	51	51
GNAO1	0.021	0.029	0.23	2	-0.53	1	3
HRAS	0.022	0.004	-10000	0	-10000	0	0
SHBG/T-DHT	0.014	0.004	-10000	0	-10000	0	0
PELP1	0.021	0.006	-10000	0	-10000	0	0
AKT1	-0.004	0.003	-10000	0	-10000	0	0
MAP2K1	-0.069	0.11	-10000	0	-0.28	85	85
T-DHT/AR	-0.068	0.16	-10000	0	-0.38	103	103
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.002	-10000	0	-0.006	60	60
GNAI2	0.021	0.007	-10000	0	-10000	0	0
GNAI3	0.022	0.005	-10000	0	-10000	0	0
GNAI1	0.021	0.025	-10000	0	-0.53	1	1
mol:GDP	-0.078	0.15	-10000	0	-0.37	102	102
cell proliferation	-0.097	0.17	-10000	0	-0.44	71	71
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
FOS	-0.12	0.27	-10000	0	-0.8	62	62
mol:Ca2+	-0.009	0.022	-10000	0	-0.067	35	35
MAPK3	-0.087	0.14	-10000	0	-0.42	36	36
MAPK1	-0.044	0.11	-10000	0	-0.36	24	24
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
mol:IP3	0	0.001	-10000	0	-0.004	60	60
cAMP biosynthetic process	0.002	0.017	-10000	0	-10000	0	0
GNG2	0.016	0.055	-10000	0	-0.53	5	5
potassium channel inhibitor activity	0	0.001	-10000	0	-0.004	60	60
HRAS/GTP	-0.032	0.13	-10000	0	-0.28	97	97
actin cytoskeleton reorganization	0.017	0.018	-10000	0	-10000	0	0
SRC	0.022	0.004	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.004	60	60
PI3K	0.016	0.016	-10000	0	-10000	0	0
apoptosis	0.076	0.16	0.44	67	-10000	0	67
T-DHT/AR/PELP1	-0.048	0.14	-10000	0	-0.33	100	100
HRAS/GDP	-0.064	0.15	-10000	0	-0.36	101	101
CREB1	-0.082	0.17	-10000	0	-0.47	67	67
RAC1-CDC42/GTP	0.022	0.022	-10000	0	-10000	0	0
AR	-0.091	0.22	-10000	0	-0.53	100	100
GNB1	0.021	0.025	-10000	0	-0.53	1	1
RAF1	-0.066	0.11	0.2	1	-0.28	90	91
RAC1-CDC42/GDP	-0.024	0.17	-10000	0	-0.34	98	98
T-DHT/AR/PELP1/Src	-0.035	0.14	-10000	0	-0.31	97	97
MAP2K2	-0.069	0.11	-10000	0	-0.28	85	85
T-DHT/AR/PELP1/Src/PI3K	-0.033	0.09	-10000	0	-0.26	51	51
GNAZ	0.016	0.056	-10000	0	-0.53	5	5
SHBG	0.02	0.01	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.032	0.16	-10000	0	-0.52	35	35
mol:T-DHT	0	0.001	0.001	2	-0.002	39	41
RAC1	0.022	0.004	-10000	0	-10000	0	0
GNRH1	-0.006	0.024	-10000	0	-0.39	2	2
Gi family/GTP	-0.03	0.084	-10000	0	-0.31	21	21
CDC42	0.022	0.004	-10000	0	-10000	0	0

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	0.07	0.14	0.3	25	-0.31	42	67
SMAD6-7/SMURF1	0.009	0.1	-10000	0	-0.33	40	40
NOG	0.001	0.1	0.23	1	-0.53	18	19
SMAD9	-0.085	0.22	-10000	0	-0.52	92	92
SMAD4	0.022	0.005	-10000	0	-10000	0	0
SMAD5	-0.034	0.14	-10000	0	-0.47	28	28
BMP7/USAG1	-0.012	0.2	0.27	3	-0.41	94	97
SMAD5/SKI	-0.036	0.16	0.26	1	-0.47	39	40
SMAD1	0.008	0.059	-10000	0	-0.61	2	2
BMP2	-0.043	0.18	-10000	0	-0.53	58	58
SMAD1/SMAD1/SMAD4	-0.012	0.1	-10000	0	-0.48	5	5
BMPR1A	0.022	0.005	-10000	0	-10000	0	0
BMPR1B	-0.02	0.14	-10000	0	-0.53	37	37
BMPR1A-1B/BAMBI	0.012	0.1	0.25	1	-0.34	40	41
AHSG	0.019	0.065	0.35	17	-10000	0	17
CER1	-0.008	0.024	0.23	1	-0.3	1	2
BMP2-4/CER1	-0.014	0.13	-10000	0	-0.35	63	63
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.035	0.15	-10000	0	-0.45	36	36
BMP2-4 (homodimer)	-0.027	0.15	-10000	0	-0.4	65	65
RGMB	0.021	0.006	-10000	0	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	0.017	0.11	-10000	0	-0.32	46	46
RGMA	0.046	0.076	0.25	54	-0.53	1	55
SMURF1	0.021	0.006	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.028	0.12	-10000	0	-0.45	23	23
BMP2-4/USAG1	-0.074	0.19	-10000	0	-0.38	133	133
SMAD6/SMURF1/SMAD5	-0.033	0.15	0.31	2	-0.46	40	42
SOSTDC1	-0.08	0.22	0.23	1	-0.53	92	93
BMP7/BMPR2/BMPR1A-1B	0.052	0.13	-10000	0	-0.32	42	42
SKI	0.022	0.005	-10000	0	-10000	0	0
BMP6 (homodimer)	0.01	0.082	-10000	0	-0.53	11	11
HFE2	-0.003	0.024	0.23	2	-10000	0	2
ZFYVE16	0.021	0.006	-10000	0	-10000	0	0
MAP3K7	0.023	0.002	-10000	0	-10000	0	0
BMP2-4/CHRD	-0.015	0.11	0.25	1	-0.36	42	43
SMAD5/SMAD5/SMAD4	-0.035	0.16	0.31	2	-0.47	39	41
MAPK1	0.021	0.006	-10000	0	-10000	0	0
TAK1/TAB family	-0.015	0.12	-10000	0	-0.39	23	23
BMP7 (homodimer)	0.082	0.12	0.23	161	-0.47	8	169
NUP214	0.022	0.003	-10000	0	-10000	0	0
BMP6/FETUA	0.019	0.067	0.27	12	-0.39	7	19
SMAD1/SKI	0.007	0.086	-10000	0	-0.53	4	4
SMAD6	-0.031	0.16	-10000	0	-0.53	48	48
CTDSP2	0.022	0.003	-10000	0	-10000	0	0
BMP2-4/FETUA	-0.007	0.12	0.25	13	-0.35	43	56
MAP3K7IP1	0	0	-10000	0	-10000	0	0
GREM1	0.15	0.11	0.23	298	-0.3	2	300
BMPR2 (homodimer)	0.022	0.004	-10000	0	-10000	0	0
GADD34/PP1CA	0.042	0.014	-10000	0	-10000	0	0
BMPR1A-1B (homodimer)	0	0.11	-10000	0	-0.39	37	37
CHRDL1	-0.26	0.28	-10000	0	-0.53	255	255
ENDOFIN/SMAD1	0.009	0.084	-10000	0	-0.52	4	4
SMAD6-7/SMURF1/SMAD1	-0.002	0.12	-10000	0	-0.53	5	5
SMAD6/SMURF1	0.021	0.006	-10000	0	-10000	0	0
BAMBI	0.02	0.047	0.3	2	-0.53	3	5
SMURF2	0.022	0.003	-10000	0	-10000	0	0
BMP2-4/CHRDL1	-0.19	0.22	-10000	0	-0.38	261	261
BMP2-4/GREM1	0.053	0.18	0.25	1	-0.37	64	65
SMAD7	0.022	0.005	-10000	0	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.084	0.22	-10000	0	-0.51	99	99
SMAD1/SMAD6	0.006	0.085	-10000	0	-0.54	4	4
TAK1/SMAD6	0.032	0.009	-10000	0	-10000	0	0
BMP7	0.082	0.12	0.23	161	-0.48	8	169
BMP6	0.01	0.082	-10000	0	-0.53	11	11
MAP3K7IP2	0	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.022	0.12	-10000	0	-0.41	25	25
PPM1A	0.022	0.004	-10000	0	-10000	0	0
SMAD1/SMURF2	0.006	0.085	-10000	0	-0.5	4	4
SMAD7/SMURF1	0.03	0.01	-10000	0	-10000	0	0
CTDSPL	0.021	0.007	-10000	0	-10000	0	0
PPP1CA	0.022	0.004	-10000	0	-10000	0	0
XIAP	0.022	0.003	-10000	0	-10000	0	0
CTDSP1	0.022	0.004	-10000	0	-10000	0	0
PPP1R15A	0.022	0.004	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.034	0.15	-10000	0	-0.46	34	34
CHRD	0.011	0.04	0.38	1	-0.53	2	3
BMPR2	0.022	0.004	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.036	0.12	0.2	1	-0.46	24	25
BMP4	0.01	0.082	0.23	1	-0.53	11	12
FST	0.049	0.091	0.24	77	-0.33	7	84
BMP2-4/NOG	-0.02	0.15	-10000	0	-0.36	73	73
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	0.059	0.12	-10000	0	-0.3	36	36

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.01	0.091	-10000	0	-0.39	24	24
alphaV beta3 Integrin	0.026	0.08	-10000	0	-0.35	20	20
PTK2	-0.16	0.19	0.34	2	-0.52	62	64
IGF1R	0.022	0.004	-10000	0	-10000	0	0
PI4KB	0.021	0.006	-10000	0	-10000	0	0
MFGE8	0.022	0.003	-10000	0	-10000	0	0
SRC	0.022	0.004	-10000	0	-10000	0	0
CDKN1B	-0.17	0.24	-10000	0	-0.48	183	183
VEGFA	0.022	0.004	-10000	0	-10000	0	0
ILK	-0.17	0.24	-10000	0	-0.48	185	185
ROCK1	0.022	0.004	-10000	0	-10000	0	0
AKT1	-0.15	0.22	-10000	0	-0.45	171	171
PTK2B	-0.018	0.094	0.35	2	-0.34	26	28
alphaV/beta3 Integrin/JAM-A	-0.086	0.17	-10000	0	-0.31	172	172
CBL	0.022	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.035	0.056	-10000	0	-0.34	10	10
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.043	0.067	-10000	0	-0.31	16	16
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.091	0.16	-10000	0	-0.44	50	50
alphaV/beta3 Integrin/Syndecan-1	0.035	0.057	-10000	0	-0.34	11	11
PI4KA	0.021	0.006	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.015	0.11	-10000	0	-0.33	40	40
PI4 Kinase	0.03	0.011	-10000	0	-10000	0	0
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	0.093	0.098	0.25	1	-0.35	10	11
RPS6KB1	-0.036	0.098	0.32	2	-0.45	11	13
TLN1	0.021	0.007	-10000	0	-10000	0	0
MAPK3	-0.08	0.16	-10000	0	-0.55	38	38
GPR124	0.018	0.026	-10000	0	-0.53	1	1
MAPK1	-0.078	0.16	-10000	0	-0.56	37	37
PXN	0.023	0.002	-10000	0	-10000	0	0
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.19	0.19	-10000	0	-0.35	292	292
cell adhesion	0.025	0.054	-10000	0	-0.33	9	9
ANGPTL3	0.007	0.028	0.23	4	-10000	0	4
VEGFR2 homodimer/VEGFA homodimer/Src	0.024	0.077	-10000	0	-0.33	20	20
IGF-1R heterotetramer	0.022	0.004	-10000	0	-10000	0	0
Rac1/GDP	0.016	0.003	-10000	0	-10000	0	0
TGFBR2	-0.007	0.12	-10000	0	-0.53	25	25
ITGB3	0.01	0.082	-10000	0	-0.53	11	11
IGF1	0.003	0.1	0.23	1	-0.53	18	19
RAC1	0.022	0.004	-10000	0	-10000	0	0
regulation of cell-matrix adhesion	0.029	0.054	-10000	0	-0.34	9	9
apoptosis	0.022	0.003	-10000	0	-10000	0	0
CD47	0.019	0.026	-10000	0	-0.53	1	1
alphaV/beta3 Integrin/CD47	0.031	0.055	-10000	0	-0.34	9	9
VCL	0.022	0.005	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Del1	0.013	0.1	-10000	0	-0.35	34	34
CSF1	0.017	0.05	-10000	0	-0.53	4	4
PIK3C2A	-0.17	0.24	-10000	0	-0.48	185	185
PI4 Kinase/Pyk2	-0.086	0.16	-10000	0	-0.31	129	129
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.029	0.097	-10000	0	-0.36	26	26
FAK1/Vinculin	-0.13	0.15	0.32	2	-0.42	53	55
alphaV beta3/Integrin/ppsTEM5	0.029	0.055	-10000	0	-0.34	9	9
RHOA	0.021	0.007	-10000	0	-10000	0	0
VTN	-0.18	0.27	0.23	2	-0.53	185	187
BCAR1	0.022	0.005	-10000	0	-10000	0	0
FGF2	0.008	0.085	-10000	0	-0.53	12	12
F11R	-0.018	0.056	-10000	0	-0.39	11	11
alphaV/beta3 Integrin/Lactadherin	0.036	0.055	-10000	0	-0.34	10	10
alphaV/beta3 Integrin/TGFBR2	0.013	0.11	-10000	0	-0.39	30	30
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.049	0.035	-10000	0	-0.31	3	3
HSP90AA1	0.022	0.005	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	0.032	0.047	-10000	0	-0.31	8	8
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.009	0.085	-10000	0	-0.53	12	12
alphaV/beta3 Integrin/Pyk2	0.02	0.094	-10000	0	-0.34	26	26
SDC1	0.021	0.025	-10000	0	-0.53	1	1
VAV3	-0.012	0.04	-10000	0	-0.29	4	4
PTPN11	0.023	0.002	-10000	0	-10000	0	0
IRS1	0.022	0.004	-10000	0	-10000	0	0
FAK1/Paxillin	-0.13	0.15	0.34	1	-0.42	56	57
cell migration	-0.12	0.14	0.26	3	-0.39	51	54
ITGAV	0.022	0.004	-10000	0	-10000	0	0
PI3K	-0.048	0.13	-10000	0	-0.3	80	80
SPP1	0.12	0.11	0.23	246	-0.3	6	252
KDR	-0.007	0.12	-10000	0	-0.53	25	25
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.022	0.003	-10000	0	-10000	0	0
COL4A3	-0.31	0.27	-10000	0	-0.53	301	301
angiogenesis	-0.11	0.18	0.27	1	-0.56	40	41
Rac1/GTP	0.019	0.036	-10000	0	-0.27	4	4
EDIL3	-0.009	0.13	-10000	0	-0.53	27	27
cell proliferation	0.013	0.11	-10000	0	-0.39	30	30

×

Calcium signaling in the CD4+ TCR pathway

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
NFATC1	-0.004	0.034	-10000	0	-0.41	1	1
NFATC2	-0.047	0.12	-10000	0	-0.36	63	63
NFATC3	-0.003	0.029	-10000	0	-10000	0	0
CD40LG	-0.16	0.28	0.34	2	-0.61	112	114
PTGS2	-0.14	0.25	0.34	2	-0.57	102	104
JUNB	0.021	0.025	-10000	0	-0.53	1	1
CaM/Ca2+/Calcineurin A alpha-beta B1	0.003	0.024	-10000	0	-10000	0	0
CaM/Ca2+	0.003	0.023	-10000	0	-10000	0	0
CALM1	0.01	0.022	-10000	0	-10000	0	0
JUN	0.011	0.022	-10000	0	-10000	0	0
mol:Ca2+	-0.005	0.009	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.009	0.012	-10000	0	-10000	0	0
FOSL1	0.024	0.021	0.28	3	-10000	0	3
CREM	0.022	0.004	-10000	0	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.05	0.16	-10000	0	-0.39	58	58
FOS	-0.054	0.18	-10000	0	-0.54	58	58
IFNG	-0.12	0.22	0.34	1	-0.51	86	87
AP-1/NFAT1-c-4	-0.13	0.26	-10000	0	-0.59	89	89
FASLG	-0.13	0.23	0.34	2	-0.56	82	84
NFAT1-c-4/ICER1	-0.044	0.13	-10000	0	-0.34	58	58
IL2RA	-0.12	0.22	0.34	1	-0.51	84	85
FKBP12/FK506	0.016	0.003	-10000	0	-10000	0	0
CSF2	-0.14	0.25	0.34	2	-0.54	110	112
JunB/Fra1/NFAT1-c-4	-0.036	0.13	-10000	0	-0.34	59	59
IL4	-0.12	0.22	0.33	2	-0.51	83	85
IL2	-0.032	0.21	-10000	0	-0.93	25	25
IL3	-0.044	0.19	-10000	0	-0.7	35	35
FKBP1A	0.022	0.005	-10000	0	-10000	0	0
BATF3	0.022	0.004	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.021	0.006	-10000	0	-10000	0	0

×

Arf6 signaling events

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
CENTA1/KIF3B	0.018	0.056	-10000	0	-0.34	11	11
ARNO/beta Arrestin1-2	-0.099	0.21	-10000	0	-0.58	49	49
EGFR	0.023	0.081	0.36	12	-0.53	6	18
EPHA2	0.018	0.043	-10000	0	-0.53	3	3
USP6	0.021	0.006	-10000	0	-10000	0	0
IQSEC1	0.021	0.006	-10000	0	-10000	0	0
EGFR/EGFR/EGF/EGF	0.024	0.078	0.27	8	-0.42	12	20
ARRB2	0.007	0.004	-10000	0	-10000	0	0
mol:GTP	0.037	0.061	0.16	26	-0.18	7	33
ARRB1	-0.084	0.22	-10000	0	-0.53	95	95
FBXO8	0.021	0.006	-10000	0	-10000	0	0
TSHR	0.026	0.037	0.23	15	-10000	0	15
EGF	0.015	0.068	0.23	3	-0.53	7	10
somatostatin receptor activity	0	0	0.001	4	-0.001	108	112
ARAP2	0.02	0.026	-10000	0	-0.53	1	1
mol:GDP	-0.09	0.16	0.2	1	-0.32	113	114
mol:PI-3-4-5-P3	0	0	0.001	3	-0.001	65	68
ITGA2B	0.006	0.092	-10000	0	-0.53	14	14
ARF6	0.022	0.005	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.043	0.037	-10000	0	-0.31	3	3
ADAP1	0.015	0.061	-10000	0	-0.53	6	6
KIF13B	0.015	0.056	-10000	0	-0.53	5	5
HGF/MET	-0.054	0.17	0.27	1	-0.39	99	100
PXN	0.023	0.002	-10000	0	-10000	0	0
ARF6/GTP	-0.084	0.14	0.22	5	-0.29	109	114
EGFR/EGFR/EGF/EGF/ARFGEP100	0.034	0.071	0.25	8	-0.36	12	20
ADRB2	-0.12	0.24	-10000	0	-0.53	123	123
receptor agonist activity	0	0	0	7	0	98	105
actin filament binding	0	0	0	3	-0.001	109	112
SRC	0.022	0.004	-10000	0	-10000	0	0
ITGB3	0.01	0.082	-10000	0	-0.53	11	11
GNAQ	0.021	0.025	-10000	0	-0.53	1	1
EFA6/PI-4-5-P2	0	0.001	0.001	10	-0.001	78	88
ARF6/GDP	-0.018	0.16	0.26	8	-0.52	32	40
ARF6/GDP/GULP/ACAP1	-0.071	0.16	-10000	0	-0.37	66	66
alphaIIb/beta3 Integrin/paxillin/GIT1	0.037	0.081	-10000	0	-0.31	25	25
ACAP1	0.021	0.027	0.23	1	-0.53	1	2
ACAP2	0.014	0.011	-10000	0	-10000	0	0
LHCGR/beta Arrestin2	0.014	0.018	0.19	1	-10000	0	1
EFNA1	0.022	0.005	-10000	0	-10000	0	0
HGF	-0.09	0.22	-10000	0	-0.53	100	100
CYTH3	-0.005	0.003	-10000	0	-10000	0	0
CYTH2	-0.01	0.16	-10000	0	-1	12	12
NCK1	0.019	0.008	-10000	0	-10000	0	0
fibronectin binding	0	0	0.001	7	0	91	98
endosomal lumen acidification	0	0	0.001	22	0	71	93
microtubule-based process	0	0	-10000	0	-10000	0	0
GULP1	0.014	0.065	-10000	0	-0.53	7	7
GNAQ/ARNO	0.003	0.15	-10000	0	-0.96	12	12
mol:Phosphatidic acid	0	0	0	2	-10000	0	2
PIP3-E	0	0	0	5	0	12	17
MET	0.02	0.039	0.38	1	-0.53	2	3
GNA14	-0.11	0.24	-10000	0	-0.53	117	117
GNA15	0.022	0.004	-10000	0	-10000	0	0
GIT1	0.022	0.003	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	0.001	9	-0.001	88	97
GNA11	0.022	0.004	-10000	0	-10000	0	0
LHCGR	-0.007	0.021	0.23	1	-10000	0	1
AGTR1	-0.13	0.24	-10000	0	-0.53	132	132
desensitization of G-protein coupled receptor protein signaling pathway	0.014	0.018	0.19	1	-10000	0	1
IPCEF1/ARNO	0.009	0.15	-10000	0	-0.84	13	13
alphaIIb/beta3 Integrin	0.012	0.093	-10000	0	-0.39	25	25

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.008	0.053	0.16	37	-0.11	1	38
BUB1B	0.021	0.03	0.11	1	-0.24	3	4
PLK1	0.009	0.018	0.082	6	-0.086	1	7
PLK1S1	0.009	0.021	-10000	0	-0.19	4	4
KIF2A	0.007	0.021	0.23	3	-10000	0	3
regulation of mitotic centrosome separation	0.009	0.018	0.084	5	-0.086	1	6
GOLGA2	0.022	0.003	-10000	0	-10000	0	0
Hec1/SPC24	0.12	0.1	0.26	127	-0.29	1	128
WEE1	0.008	0.059	-10000	0	-0.33	12	12
cytokinesis	0.018	0.074	0.2	4	-0.31	14	18
PP2A-alpha B56	0.056	0.049	-10000	0	-0.49	2	2
AURKA	0.012	0.024	0.14	3	-0.19	3	6
PICH/PLK1	0.034	0.052	0.22	10	-0.23	1	11
CENPE	0.001	0.024	0.27	1	-0.2	1	2
RhoA/GTP	0.015	0.005	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.007	0.022	0.23	3	-10000	0	3
PPP2CA	0.021	0.006	-10000	0	-10000	0	0
FZR1	0.022	0.004	-10000	0	-10000	0	0
TPX2	0.054	0.042	0.17	36	-10000	0	36
PAK1	0.023	0.016	0.36	1	-10000	0	1
SPC24	0.081	0.099	0.24	137	-0.3	1	138
FBXW11	0.021	0.006	-10000	0	-10000	0	0
CLSPN	0.012	0.044	-10000	0	-0.22	13	13
GORASP1	0.021	0.006	-10000	0	-10000	0	0
metaphase	0	0.002	0.013	7	-0.012	2	9
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.004	0.01	0.045	6	-10000	0	6
G2 phase of mitotic cell cycle	-0.001	0.002	0.012	8	-0.013	1	9
STAG2	0.023	0.003	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	-0.026	0.15	-10000	0	-0.53	41	41
spindle elongation	0.009	0.018	0.084	5	-0.086	1	6
ODF2	0.023	0.004	-10000	0	-10000	0	0
BUB1	0.035	0.054	-10000	0	-0.54	2	2
TPT1	-0.003	0.05	-10000	0	-0.19	33	33
CDC25C	0.042	0.097	0.21	2	-0.29	34	36
CDC25B	0.021	0.011	-10000	0	-10000	0	0
SGOL1	0.008	0.053	0.11	1	-0.16	37	38
RHOA	0.021	0.007	-10000	0	-10000	0	0
CCNB1/CDK1	0.04	0.056	-10000	0	-0.23	2	2
CDC14B	-0.005	0.003	-10000	0	-10000	0	0
CDC20	0.16	0.11	0.23	326	-0.3	4	330
PLK1/PBIP1	0.003	0.011	-10000	0	-10000	0	0
mitosis	-0.002	0.004	0.024	3	-0.018	18	21
FBXO5	0.006	0.02	0.14	2	-10000	0	2
CDC2	0.001	0.003	-10000	0	-0.011	7	7
NDC80	0.1	0.11	0.25	173	-0.3	1	174
metaphase plate congression	0.003	0.049	-10000	0	-0.23	20	20
ERCC6L	0.031	0.054	0.2	9	-0.27	1	10
NLP/gamma Tubulin	0.006	0.014	0.11	1	-0.1	2	3
microtubule cytoskeleton organization	-0.003	0.05	-10000	0	-0.19	33	33
G2/M transition DNA damage checkpoint	-0.001	0.002	0.01	5	-10000	0	5
PPP1R12A	0.023	0.003	-10000	0	-10000	0	0
interphase	-0.001	0.002	0.01	5	-10000	0	5
PLK1/PRC1-2	0.1	0.097	0.25	70	-0.19	8	78
GRASP65/GM130/RAB1/GTP/PLK1	0.038	0.02	-10000	0	-10000	0	0
RAB1A	0.021	0.006	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.006	0.015	0.076	6	-0.072	1	7
mitotic prometaphase	0	0.004	0.018	20	-10000	0	20
proteasomal ubiquitin-dependent protein catabolic process	0.008	0.1	-10000	0	-0.46	18	18
microtubule-based process	0.086	0.084	0.17	238	-0.18	11	249
Golgi organization	0.009	0.018	0.084	5	-0.086	1	6
Cohesin/SA2	0.022	0.015	-10000	0	-10000	0	0
PPP1CB/MYPT1	0.033	0.006	-10000	0	-10000	0	0
KIF20A	0.11	0.13	0.23	242	-0.3	15	257
APC/C/CDC20	0.11	0.077	0.17	322	-0.16	5	327
PPP2R1A	0.022	0.004	-10000	0	-10000	0	0
chromosome segregation	0.003	0.011	-10000	0	-10000	0	0
PRC1	0.044	0.067	0.24	48	-10000	0	48
ECT2	0.096	0.11	0.22	217	-10000	0	217
C13orf34	0.007	0.015	0.071	6	-10000	0	6
NUDC	0.003	0.049	-10000	0	-0.23	20	20
regulation of attachment of spindle microtubules to kinetochore	0.021	0.03	0.11	1	-0.24	3	4
spindle assembly	0.007	0.017	0.12	2	-10000	0	2
spindle stabilization	0.009	0.021	-10000	0	-0.19	4	4
APC/C/HCDH1	0.019	0.005	-10000	0	-10000	0	0
MKLP2/PLK1	0.086	0.084	0.17	238	-0.18	11	249
CCNB1	0.046	0.073	0.24	60	-0.31	2	62
PPP1CB	0.023	0.004	-10000	0	-10000	0	0
BTRC	0.022	0.005	-10000	0	-10000	0	0
ROCK2	0.006	0.047	-10000	0	-0.25	4	4
TUBG1	0.008	0.024	0.11	1	-0.18	6	7
G2/M transition of mitotic cell cycle	0.004	0.028	-10000	0	-0.22	2	2
MLF1IP	-0.006	0.011	-10000	0	-10000	0	0
INCENP	0.022	0.002	-10000	0	-10000	0	0

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.023	0.015	-10000	0	-10000	0	0
AES	0.022	0.013	-10000	0	-10000	0	0
FBXW11	0.021	0.006	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.031	0.011	-10000	0	-10000	0	0
SMAD4	0.022	0.005	-10000	0	-10000	0	0
DKK2	-0.074	0.21	-10000	0	-0.53	86	86
TLE1	0.022	0.012	-10000	0	-10000	0	0
MACF1	0.02	0.035	-10000	0	-0.53	2	2
CTNNB1	0.087	0.12	0.29	32	-0.38	6	38
WIF1	-0.32	0.27	0.23	1	-0.53	307	308
beta catenin/RanBP3	0.009	0.1	0.44	17	-0.44	1	18
KREMEN2	0.15	0.11	0.23	317	-0.3	6	323
DKK1	0.021	0.089	0.24	21	-0.51	10	31
beta catenin/beta TrCP1	0.095	0.12	0.3	24	-0.36	4	28
FZD1	0.022	0.006	-10000	0	-10000	0	0
AXIN2	-0.036	0.27	0.57	7	-1.4	17	24
AXIN1	0.023	0.005	-10000	0	-10000	0	0
RAN	0.023	0.002	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.025	0.11	-10000	0	-0.56	13	13
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.051	0.13	-10000	0	-0.54	14	14
Axin1/APC/GSK3	0.057	0.076	0.26	10	-0.34	2	12
Axin1/APC/GSK3/beta catenin/Macf1	0.047	0.099	0.28	10	-0.36	6	16
HNF1A	0.026	0.029	0.23	8	-10000	0	8
CTBP1	0.021	0.014	-10000	0	-10000	0	0
MYC	0.055	0.18	0.58	48	-10000	0	48
RANBP3	0.022	0.004	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.026	0.19	-10000	0	-0.37	80	80
NKD1	-0.022	0.15	0.23	4	-0.53	40	44
TCF4	0.019	0.044	-10000	0	-0.52	3	3
TCF3	0.022	0.013	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0.052	0.024	-10000	0	-10000	0	0
Ran/GTP	0.017	0.002	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	-0.006	0.11	0.4	15	-0.4	13	28
LEF1	0.023	0.017	0.23	1	-10000	0	1
DVL1	0.053	0.078	0.23	1	-0.52	4	5
CSNK2A1	0.022	0.005	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.049	0.15	-10000	0	-0.63	13	13
DKK1/LRP6/Kremen 2	0.11	0.11	0.31	15	-0.36	10	25
LRP6	0.022	0.006	-10000	0	-10000	0	0
CSNK1A1	0.022	0.015	-10000	0	-10000	0	0
NLK	0.021	0.009	-10000	0	-10000	0	0
CCND1	0.062	0.26	0.58	67	-1.4	6	73
WNT1	0.022	0.019	0.23	3	-10000	0	3
GSK3A	0.023	0.005	-10000	0	-10000	0	0
GSK3B	0.02	0.007	-10000	0	-10000	0	0
FRAT1	0.02	0.025	-10000	0	-0.53	1	1
PPP2R5D	0.067	0.085	0.32	39	-0.37	1	40
APC	0.014	0.066	0.2	50	-10000	0	50
WNT1/LRP6/FZD1	0.13	0.11	0.23	280	-10000	0	280
CREBBP	0.022	0.013	-10000	0	-10000	0	0

×

IL6-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.15	0.23	-10000	0	-0.68	16	16
CRP	-0.15	0.23	-10000	0	-0.65	21	21
cell cycle arrest	-0.18	0.26	-10000	0	-0.63	54	54
TIMP1	-0.12	0.21	-10000	0	-0.62	17	17
IL6ST	-0.01	0.098	-10000	0	-0.53	16	16
Rac1/GDP	-0.066	0.16	-10000	0	-0.4	57	57
AP1	0.038	0.16	-10000	0	-0.59	9	9
GAB2	0.014	0.093	-10000	0	-0.53	14	14
TNFSF11	-0.15	0.23	-10000	0	-0.69	16	16
HSP90B1	-0.002	0.088	-10000	0	-0.76	5	5
GAB1	0.026	0.01	-10000	0	-10000	0	0
MAPK14	-0.044	0.14	-10000	0	-0.55	19	19
AKT1	0.039	0.073	0.29	6	-0.36	3	9
FOXO1	0.037	0.07	0.28	6	-0.36	1	7
MAP2K6	-0.055	0.14	-10000	0	-0.39	52	52
mol:GTP	-0.002	0.003	-10000	0	-10000	0	0
MAP2K4	-0.089	0.17	-10000	0	-0.45	54	54
MITF	-0.062	0.15	-10000	0	-0.39	59	59
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.022	0.004	-10000	0	-10000	0	0
A2M	-0.44	0.65	-10000	0	-1.4	165	165
CEBPB	0.026	0.005	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.027	0.13	0.27	2	-0.51	11	13
STAT3	-0.18	0.27	-10000	0	-0.67	53	53
STAT1	-0.006	0.1	-10000	0	-0.85	7	7
CEBPD	-0.15	0.24	-10000	0	-0.62	34	34
PIK3CA	0.013	0.012	-10000	0	-10000	0	0
PI3K	0.018	0.017	-10000	0	-10000	0	0
JUN	0.022	0.004	-10000	0	-10000	0	0
PIAS3/MITF	-0.056	0.15	-10000	0	-0.38	58	58
MAPK11	-0.044	0.14	-10000	0	-0.54	20	20
STAT3 (dimer)/FOXO1	-0.2	0.3	0.4	1	-0.64	104	105
GRB2/SOS1/GAB family	0.007	0.16	-10000	0	-0.46	22	22
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.046	0.15	-10000	0	-0.36	67	67
GRB2	0.027	0.008	-10000	0	-10000	0	0
JAK2	0.02	0.007	-10000	0	-10000	0	0
LBP	-0.093	0.19	-10000	0	-0.62	9	9
PIK3R1	0.021	0.007	-10000	0	-10000	0	0
JAK1	0.014	0.02	-10000	0	-10000	0	0
MYC	-0.14	0.24	-10000	0	-0.58	40	40
FGG	-0.46	0.53	-10000	0	-1	233	233
macrophage differentiation	-0.18	0.26	-10000	0	-0.63	54	54
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.029	0.15	-10000	0	-0.34	77	77
JUNB	-0.15	0.23	-10000	0	-0.65	20	20
FOS	-0.043	0.18	-10000	0	-0.53	58	58
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.063	0.16	-10000	0	-0.39	65	65
STAT1/PIAS1	-0.067	0.16	-10000	0	-0.4	59	59
GRB2/SOS1/GAB family/SHP2/PI3K	0.038	0.071	-10000	0	-0.37	4	4
STAT3 (dimer)	-0.18	0.27	-10000	0	-0.66	53	53
PRKCD	-0.11	0.2	0.3	3	-0.5	51	54
IL6R	0.004	0.076	-10000	0	-0.53	9	9
SOCS3	-0.032	0.15	-10000	0	-0.63	15	15
gp130 (dimer)/JAK1/JAK1/LMO4	0.012	0.076	-10000	0	-0.33	16	16
Rac1/GTP	-0.076	0.17	-10000	0	-0.43	56	56
HCK	0.02	0.043	-10000	0	-0.53	3	3
MAPKKK cascade	0.046	0.14	-10000	0	-0.58	9	9
bone resorption	-0.15	0.22	-10000	0	-0.64	17	17
IRF1	-0.16	0.23	-10000	0	-0.68	17	17
mol:GDP	-0.067	0.15	-10000	0	-0.41	55	55
SOS1	0.029	0.012	-10000	0	-10000	0	0
VAV1	-0.068	0.15	-10000	0	-0.42	55	55
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.033	0.16	-10000	0	-0.58	26	26
PTPN11	0.008	0.057	-10000	0	-0.81	2	2
IL6/IL6RA	-0.049	0.16	-10000	0	-0.42	74	74
gp130 (dimer)/TYK2/TYK2/LMO4	0.015	0.072	-10000	0	-0.33	16	16
gp130 (dimer)/JAK2/JAK2/LMO4	0.014	0.072	-10000	0	-0.33	16	16
IL6	-0.076	0.2	-10000	0	-0.54	77	77
PIAS3	0.021	0.007	-10000	0	-10000	0	0
PTPRE	0.02	0.04	-10000	0	-0.53	2	2
PIAS1	0.023	0.002	-10000	0	-10000	0	0
RAC1	0.021	0.004	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.055	0.14	-10000	0	-0.34	81	81
LMO4	0.008	0.026	0.21	1	-10000	0	1
STAT3 (dimer)/PIAS3	-0.16	0.26	-10000	0	-0.65	50	50
MCL1	0.048	0.082	0.45	3	-10000	0	3

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	0.03	0.033	0.24	12	-10000	0	12
NFATC2	-0.04	0.22	-10000	0	-0.56	68	68
NFATC3	0.011	0.064	-10000	0	-0.27	9	9
CD40LG	-0.17	0.35	-10000	0	-0.88	70	70
ITCH	-0.018	0.095	-10000	0	-10000	0	0
CBLB	-0.019	0.093	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.1	0.28	-10000	0	-0.81	45	45
JUNB	0.021	0.025	-10000	0	-0.53	1	1
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.023	0.12	-10000	0	-0.29	79	79
T cell anergy	-0.05	0.16	0.29	3	-0.41	69	72
TLE4	-0.029	0.16	-10000	0	-0.47	38	38
Jun/NFAT1-c-4/p21SNFT	-0.047	0.26	-10000	0	-0.91	26	26
AP-1/NFAT1-c-4	-0.12	0.36	-10000	0	-1	39	39
IKZF1	-0.032	0.19	-10000	0	-0.59	33	33
T-helper 2 cell differentiation	-0.074	0.25	-10000	0	-0.79	37	37
AP-1/NFAT1	-0.065	0.2	-10000	0	-0.4	97	97
CALM1	-0.004	0.075	-10000	0	-10000	0	0
EGR2	-0.064	0.29	-10000	0	-1.1	27	27
EGR3	-0.067	0.29	-10000	0	-1.1	25	25
NFAT1/FOXP3	-0.006	0.17	-10000	0	-0.46	37	37
EGR1	0.01	0.074	-10000	0	-0.53	9	9
JUN	0.004	0.034	-10000	0	-10000	0	0
EGR4	0.026	0.035	0.24	11	-10000	0	11
mol:Ca2+	-0.022	0.066	-10000	0	-0.17	78	78
GBP3	-0.042	0.2	-10000	0	-0.61	37	37
FOSL1	0.024	0.021	0.28	3	-10000	0	3
NFAT1-c-4/MAF/IRF4	-0.034	0.25	-10000	0	-0.93	24	24
DGKA	-0.029	0.16	-10000	0	-0.51	26	26
CREM	0.022	0.004	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.073	0.27	-10000	0	-0.9	29	29
CTLA4	-0.021	0.14	-10000	0	-0.49	20	20
NFAT1-c-4 (dimer)/EGR1	-0.044	0.26	-10000	0	-0.99	23	23
NFAT1-c-4 (dimer)/EGR4	-0.036	0.25	-10000	0	-0.94	23	23
FOS	-0.06	0.18	-10000	0	-0.54	58	58
IFNG	-0.11	0.31	-10000	0	-0.8	64	64
T cell activation	-0.064	0.18	-10000	0	-0.67	19	19
MAF	0.022	0.005	-10000	0	-10000	0	0
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.029	0.16	0.73	17	-10000	0	17
TNF	-0.062	0.24	-10000	0	-0.86	30	30
FASLG	-0.13	0.42	-10000	0	-1.5	39	39
TBX21	-0.031	0.17	-10000	0	-0.53	49	49
BATF3	0.022	0.004	-10000	0	-10000	0	0
PRKCQ	-0.026	0.16	-10000	0	-0.54	42	42
PTPN1	-0.029	0.16	-10000	0	-0.53	24	24
NFAT1-c-4/ICER1	-0.039	0.25	-10000	0	-0.93	23	23
GATA3	0.009	0.09	0.23	3	-0.53	13	16
T-helper 1 cell differentiation	-0.11	0.3	-10000	0	-0.78	64	64
IL2RA	-0.094	0.28	-10000	0	-0.78	48	48
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.026	0.15	-10000	0	-0.51	26	26
E2F1	0.024	0.006	-10000	0	-10000	0	0
PPARG	-0.036	0.17	-10000	0	-0.53	51	51
SLC3A2	-0.029	0.16	-10000	0	-0.53	24	24
IRF4	0.015	0.061	-10000	0	-0.53	6	6
PTGS2	-0.15	0.32	-10000	0	-0.85	61	61
CSF2	-0.16	0.32	-10000	0	-0.86	54	54
JunB/Fra1/NFAT1-c-4	-0.029	0.24	-10000	0	-0.89	23	23
IL4	-0.077	0.26	-10000	0	-0.83	37	37
IL5	-0.13	0.29	-10000	0	-0.9	38	38
IL2	-0.065	0.19	-10000	0	-0.68	19	19
IL3	-0.043	0.16	-10000	0	-0.78	18	18
RNF128	-0.082	0.24	-10000	0	-0.61	81	81
NFATC1	-0.03	0.17	-10000	0	-0.73	17	17
CDK4	0.039	0.15	0.58	14	-10000	0	14
PTPRK	-0.029	0.16	-10000	0	-0.53	24	24
IL8	-0.13	0.3	-10000	0	-0.9	39	39
POU2F1	0.021	0.006	-10000	0	-10000	0	0

×

Coregulation of Androgen receptor activity

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
NRIP1	0.022	0.005	-10000	0	-10000	0	0
SVIL	0.022	0.004	-10000	0	-10000	0	0
ZNF318	0.022	0.005	-10000	0	-10000	0	0
JMJD2C	0.006	0.011	0.055	1	-10000	0	1
T-DHT/AR/Ubc9	-0.075	0.16	-10000	0	-0.36	100	100
CARM1	0.022	0.004	-10000	0	-10000	0	0
PRDX1	0.022	0.004	-10000	0	-10000	0	0
PELP1	0.021	0.005	-10000	0	-10000	0	0
CTNNB1	0.021	0.006	-10000	0	-10000	0	0
AKT1	0.021	0.005	-10000	0	-10000	0	0
PTK2B	0.021	0.007	-10000	0	-10000	0	0
MED1	0.022	0.004	-10000	0	-10000	0	0
MAK	-0.026	0.16	-10000	0	-0.53	43	43
response to oxidative stress	0	0	-10000	0	-10000	0	0
HIP1	0.022	0.004	-10000	0	-10000	0	0
GSN	0.023	0.003	-10000	0	-10000	0	0
NCOA2	0.021	0.025	-10000	0	-0.53	1	1
NCOA6	0.022	0.005	-10000	0	-10000	0	0
DNA-PK	0.042	0.013	-10000	0	-10000	0	0
NCOA4	0.022	0.005	-10000	0	-10000	0	0
PIAS3	0.021	0.007	-10000	0	-10000	0	0
cell proliferation	-0.088	0.24	-10000	0	-0.77	51	51
XRCC5	0.022	0.004	-10000	0	-10000	0	0
UBE3A	0.022	0.004	-10000	0	-10000	0	0
T-DHT/AR/SNURF	-0.085	0.17	-10000	0	-0.38	110	110
FHL2	-0.028	0.07	-10000	0	-0.34	3	3
RANBP9	0.022	0.004	-10000	0	-10000	0	0
JMJD1A	-0.039	0.063	-10000	0	-0.13	160	160
CDK6	0.023	0.023	0.38	2	-10000	0	2
TGFB1I1	0.023	0.003	-10000	0	-10000	0	0
T-DHT/AR/CyclinD1	-0.071	0.15	0.26	1	-0.36	95	96
XRCC6	0.022	0.004	-10000	0	-10000	0	0
T-DHT/AR	-0.094	0.18	-10000	0	-0.38	105	105
CTDSP1	0.022	0.004	-10000	0	-10000	0	0
CTDSP2	0.022	0.004	-10000	0	-10000	0	0
BRCA1	0.022	0.003	-10000	0	-10000	0	0
TCF4	0.018	0.043	-10000	0	-0.53	3	3
CDKN2A	0.091	0.14	0.23	207	-0.31	20	227
SRF	0.026	0.005	-10000	0	-10000	0	0
NKX3-1	-0.096	0.12	-10000	0	-0.23	217	217
KLK3	0.016	0.048	-10000	0	-10000	0	0
TMF1	0.02	0.007	-10000	0	-10000	0	0
HNRNPA1	0.023	0.002	-10000	0	-10000	0	0
AOF2	0	0.001	-10000	0	-10000	0	0
APPL1	-0.009	0.004	-10000	0	-10000	0	0
T-DHT/AR/Caspase 8	-0.074	0.15	-10000	0	-0.36	99	99
AR	-0.12	0.22	-10000	0	-0.56	100	100
UBA3	0.02	0.007	-10000	0	-10000	0	0
PATZ1	0.022	0.005	-10000	0	-10000	0	0
PAWR	0.023	0.002	-10000	0	-10000	0	0
PRKDC	0.022	0.005	-10000	0	-10000	0	0
PA2G4	0.022	0.002	-10000	0	-10000	0	0
UBE2I	0.022	0.004	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.067	0.14	-10000	0	-0.33	100	100
RPS6KA3	0.022	0.005	-10000	0	-10000	0	0
T-DHT/AR/ARA70	-0.075	0.16	-10000	0	-0.36	99	99
LATS2	0.021	0.006	-10000	0	-10000	0	0
T-DHT/AR/PRX1	-0.067	0.14	-10000	0	-0.33	100	100
Cyclin D3/CDK11 p58	0.016	0.003	-10000	0	-10000	0	0
VAV3	0.021	0.025	-10000	0	-0.53	1	1
KLK2	-0.038	0.084	-10000	0	-0.42	7	7
CASP8	0.022	0.004	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.059	0.15	-10000	0	-0.33	99	99
TMPRSS2	-0.32	0.46	-10000	0	-0.97	161	161
CCND1	0.014	0.063	0.38	1	-0.53	6	7
PIAS1	0.023	0.002	-10000	0	-10000	0	0
mol:T-DHT	-0.017	0.029	-10000	0	-0.066	119	119
CDC2L1	0	0	-10000	0	-10000	0	0
PIAS4	0.022	0.004	-10000	0	-10000	0	0
T-DHT/AR/CDK6	-0.069	0.15	0.24	2	-0.36	93	95
CMTM2	-0.043	0.18	-10000	0	-0.53	56	56
SNURF	0.004	0.095	-10000	0	-0.53	15	15
ZMIZ1	-0.003	0.042	-10000	0	-10000	0	0
CCND3	0.022	0.004	-10000	0	-10000	0	0
TGIF1	0.021	0.005	-10000	0	-10000	0	0
FKBP4	0.022	0.017	0.38	1	-10000	0	1

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.035	0.02	-10000	0	-10000	0	0
VLDLR	0.019	0.026	-10000	0	-0.53	1	1
CRKL	0.021	0.006	-10000	0	-10000	0	0
LRPAP1	0.021	0.006	-10000	0	-10000	0	0
FYN	0.021	0.025	-10000	0	-0.53	1	1
ITGA3	0.018	0.05	-10000	0	-0.53	4	4
RELN/VLDLR/Fyn	-0.02	0.14	-10000	0	-0.34	76	76
MAPK8IP1/MKK7/MAP3K11/JNK1	0.059	0.029	-10000	0	-0.29	1	1
AKT1	-0.023	0.076	-10000	0	-0.26	28	28
MAP2K7	0.022	0.004	-10000	0	-10000	0	0
RAPGEF1	0.022	0.003	-10000	0	-10000	0	0
DAB1	0.026	0.056	0.24	29	-10000	0	29
RELN/LRP8/DAB1	-0.009	0.13	0.29	1	-0.31	78	79
LRPAP1/LRP8	0.031	0.013	-10000	0	-10000	0	0
RELN/LRP8/DAB1/Fyn	0	0.13	0.29	1	-0.3	78	79
DAB1/alpha3/beta1 Integrin	-0.006	0.12	-10000	0	-0.28	65	65
long-term memory	-0.01	0.15	0.3	2	-0.31	86	88
DAB1/LIS1	0.005	0.13	-10000	0	-0.28	71	71
DAB1/CRLK/C3G	-0.003	0.11	-10000	0	-0.28	56	56
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
DAB1/NCK2	0.007	0.13	0.27	1	-0.28	71	72
ARHGEF2	0.022	0.005	-10000	0	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	0.006	0.12	0.24	24	-0.53	22	46
CDK5R1	0.027	0.032	0.24	10	-10000	0	10
RELN	-0.065	0.2	0.23	3	-0.53	78	81
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
RELN/LRP8/Fyn	-0.017	0.14	-10000	0	-0.34	78	78
GRIN2A/RELN/LRP8/DAB1/Fyn	0	0.16	0.3	2	-0.32	91	93
MAPK8	0.022	0.004	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.012	0.13	0.33	2	-0.3	76	78
ITGB1	0.022	0.004	-10000	0	-10000	0	0
MAP1B	-0.046	0.11	0.28	2	-0.3	74	76
RELN/LRP8	-0.018	0.14	-10000	0	-0.33	78	78
GRIN2B/RELN/LRP8/DAB1/Fyn	0.01	0.14	0.3	1	-0.3	72	73
PI3K	0.017	0.017	-10000	0	-10000	0	0
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.029	0.035	-10000	0	-0.39	3	3
RAP1A	-0.035	0.11	0.34	8	-0.3	2	10
PAFAH1B1	0.022	0.005	-10000	0	-10000	0	0
MAPK8IP1	0.021	0.027	0.23	1	-0.53	1	2
CRLK/C3G	0.031	0.01	-10000	0	-10000	0	0
GRIN2B	0	0.03	0.23	5	-10000	0	5
NCK2	0.023	0.002	-10000	0	-10000	0	0
neuron differentiation	-0.012	0.09	0.19	1	-0.34	12	13
neuron adhesion	-0.037	0.11	0.33	11	-0.33	1	12
LRP8	0.023	0.016	0.23	3	-10000	0	3
GSK3B	-0.022	0.069	-10000	0	-0.26	27	27
RELN/VLDLR/DAB1/Fyn	-0.003	0.13	0.32	2	-0.29	76	78
MAP3K11	0.023	0.002	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.021	0.085	-10000	0	-0.27	39	39
CDK5	0.022	0.004	-10000	0	-10000	0	0
MAPT	0.007	0.12	0.76	10	-0.49	6	16
neuron migration	-0.014	0.12	0.4	1	-0.33	31	32
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.012	0.091	0.19	1	-0.34	12	13
RELN/VLDLR	-0.007	0.13	-10000	0	-0.3	76	76

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	0.024	0.06	-10000	0	-0.39	10	10
AKT1	-0.006	0.18	0.36	11	-0.54	31	42
PTK2B	-0.059	0.18	0.37	6	-0.65	27	33
VEGFR2 homodimer/Frs2	-0.056	0.19	-10000	0	-0.45	80	80
CAV1	-0.12	0.24	-10000	0	-0.53	127	127
CALM1	0.022	0.005	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.04	0.18	-10000	0	-0.42	74	74
endothelial cell proliferation	-0.012	0.18	0.37	14	-0.54	29	43
mol:Ca2+	-0.041	0.17	0.36	3	-0.62	24	27
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.028	0.18	-10000	0	-0.65	24	24
RP11-342D11.1	-0.057	0.17	-10000	0	-0.64	24	24
CDH5	-0.085	0.22	-10000	0	-0.53	96	96
VEGFA homodimer	0.05	0.022	-10000	0	-10000	0	0
SHC1	0.022	0.005	-10000	0	-10000	0	0
SHC2	0.019	0.043	-10000	0	-0.53	3	3
HRAS/GDP	-0.025	0.15	-10000	0	-0.55	24	24
SH2D2A	0.021	0.025	-10000	0	-0.53	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.023	0.17	-10000	0	-0.57	28	28
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.039	0.18	-10000	0	-0.42	73	73
VEGFR1 homodimer	0.021	0.006	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.013	0.17	-10000	0	-0.6	24	24
GRB10	-0.042	0.17	0.35	2	-0.63	24	26
PTPN11	0.023	0.002	-10000	0	-10000	0	0
GRB2	0.022	0.004	-10000	0	-10000	0	0
PAK1	0.023	0.016	0.38	1	-10000	0	1
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.074	0.24	-10000	0	-0.64	55	55
HRAS	0.022	0.004	-10000	0	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	-0.037	0.13	-10000	0	-0.44	35	35
HIF1A	0.022	0.004	-10000	0	-10000	0	0
FRS2	0.022	0.005	-10000	0	-10000	0	0
oxygen and reactive oxygen species metabolic process	-0.029	0.18	-10000	0	-0.64	24	24
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	-0.006	0.12	-10000	0	-0.53	24	24
Nck/Pak	0.028	0.013	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.041	0.19	-10000	0	-0.41	83	83
mol:GDP	-0.02	0.16	-10000	0	-0.58	24	24
mol:NADP	-0.016	0.17	0.35	9	-0.5	32	41
eNOS/Hsp90	-0.008	0.16	0.35	8	-0.46	32	40
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
mol:IP3	-0.042	0.17	0.36	3	-0.63	24	27
HIF1A/ARNT	0.031	0.01	-10000	0	-10000	0	0
SHB	0.021	0.007	-10000	0	-10000	0	0
VEGFA	0.023	0.004	-10000	0	-10000	0	0
VEGFC	0.019	0.036	-10000	0	-0.53	2	2
FAK1/Vinculin	-0.042	0.21	0.34	4	-0.62	38	42
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.021	0.007	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.034	0.19	-10000	0	-0.67	28	28
PTPN6	0.021	0.006	-10000	0	-10000	0	0
EPAS1	-0.077	0.22	-10000	0	-0.54	91	91
mol:L-citrulline	-0.016	0.17	0.35	9	-0.5	32	41
ITGAV	0.022	0.004	-10000	0	-10000	0	0
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.028	0.18	-10000	0	-0.65	24	24
VEGFR2 homodimer/VEGFA homodimer	-0.039	0.18	-10000	0	-0.69	24	24
VEGFR2/3 heterodimer	-0.072	0.22	-10000	0	-0.47	94	94
VEGFB	0.023	0.002	-10000	0	-10000	0	0
MAPK11	-0.043	0.18	0.41	5	-0.59	29	34
VEGFR2 homodimer	-0.069	0.21	-10000	0	-0.52	76	76
FLT1	0.021	0.006	-10000	0	-10000	0	0
NEDD4	0.023	0.003	-10000	0	-10000	0	0
MAPK3	-0.05	0.17	0.34	9	-0.6	25	34
MAPK1	-0.049	0.17	0.32	11	-0.6	25	36
VEGFA145/NRP2	0.03	0.034	-10000	0	-0.38	3	3
VEGFR1/2 heterodimer	-0.058	0.19	-10000	0	-0.44	83	83
KDR	-0.069	0.21	-10000	0	-0.52	76	76
VEGFA165/NRP1/VEGFR2 homodimer	-0.035	0.18	-10000	0	-0.67	24	24
SRC	0.022	0.004	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	-0.046	0.17	0.37	8	-0.61	25	33
PI3K	-0.036	0.15	-10000	0	-0.61	23	23
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.037	0.17	-10000	0	-0.43	64	64
FES	-0.045	0.18	0.36	1	-0.67	24	25
GAB1	-0.046	0.18	-10000	0	-0.61	31	31
VEGFR2 homodimer/VEGFA homodimer/Src	-0.04	0.18	-10000	0	-0.42	75	75
CTNNB1	0.021	0.006	-10000	0	-10000	0	0
SOS1	0.022	0.004	-10000	0	-10000	0	0
ARNT	0.021	0.006	-10000	0	-10000	0	0
eNOS/Caveolin-1	-0.065	0.19	0.33	4	-0.47	57	61
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.04	0.18	-10000	0	-0.41	79	79
PI3K/GAB1	-0.007	0.16	-10000	0	-0.53	27	27
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.018	0.16	-10000	0	-0.62	22	22
PRKACA	0.022	0.004	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.058	0.21	-10000	0	-0.47	78	78
HSP90AA1	0.022	0.005	-10000	0	-10000	0	0
CDC42	-0.043	0.18	0.36	3	-0.65	24	27
actin cytoskeleton reorganization	-0.039	0.18	-10000	0	-0.42	73	73
PTK2	-0.058	0.21	0.32	4	-0.62	44	48
EDG1	-0.057	0.17	-10000	0	-0.64	24	24
mol:DAG	-0.042	0.17	0.36	3	-0.63	24	27
CaM/Ca2+	-0.031	0.16	-10000	0	-0.59	23	23
MAP2K3	-0.045	0.13	-10000	0	-0.56	23	23
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.034	0.18	-10000	0	-0.66	24	24
PLCG1	-0.043	0.18	0.36	3	-0.64	24	27
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.029	0.17	-10000	0	-0.64	24	24
IQGAP1	0.022	0.004	-10000	0	-10000	0	0
YES1	0.021	0.006	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.041	0.18	-10000	0	-0.42	76	76
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.039	0.18	-10000	0	-0.41	78	78
cell migration	-0.056	0.2	0.41	2	-0.57	44	46
mol:PI-3-4-5-P3	-0.033	0.14	-10000	0	-0.56	23	23
FYN	0.021	0.025	-10000	0	-0.53	1	1
VEGFB/NRP1	-0.037	0.16	-10000	0	-0.6	24	24
mol:NO	-0.016	0.17	0.35	9	-0.5	32	41
PXN	0.023	0.002	-10000	0	-10000	0	0
HRAS/GTP	-0.036	0.14	-10000	0	-0.55	24	24
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.043	0.17	-10000	0	-0.66	24	24
VHL	0.021	0.006	-10000	0	-10000	0	0
ITGB3	0.01	0.082	-10000	0	-0.53	11	11
NOS3	-0.022	0.18	0.37	8	-0.57	32	40
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.042	0.19	-10000	0	-0.44	72	72
RAC1	0.022	0.004	-10000	0	-10000	0	0
PRKCA	-0.054	0.16	0.35	3	-0.59	25	28
PRKCB	-0.066	0.18	0.35	3	-0.64	26	29
VCL	0.022	0.005	-10000	0	-10000	0	0
VEGFA165/NRP1	-0.037	0.17	-10000	0	-0.64	24	24
VEGFR1/2 heterodimer/VEGFA homodimer	-0.042	0.18	-10000	0	-0.42	75	75
VEGFA165/NRP2	0.03	0.034	-10000	0	-0.38	3	3
MAPKKK cascade	-0.036	0.14	-10000	0	-0.54	24	24
NRP2	0.019	0.043	-10000	0	-0.53	3	3
VEGFC homodimer	0.019	0.035	-10000	0	-0.53	2	2
NCK1	0.019	0.008	-10000	0	-10000	0	0
ROCK1	0.022	0.004	-10000	0	-10000	0	0
FAK1/Paxillin	-0.042	0.21	0.38	4	-0.61	40	44
MAP3K13	-0.037	0.14	-10000	0	-0.58	23	23
PDPK1	-0.035	0.13	-10000	0	-0.5	23	23

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0.029	0.068	-10000	0	-10000	0	0
HDAC1	0.021	0.005	-10000	0	-10000	0	0
AES	0.022	0.004	-10000	0	-10000	0	0
FBXW11	0.021	0.006	-10000	0	-10000	0	0
DTX1	0.023	0.013	0.23	2	-10000	0	2
LRP6/FZD1	0.03	0.011	-10000	0	-10000	0	0
TLE1	0.022	0.004	-10000	0	-10000	0	0
AP1	-0.051	0.15	-10000	0	-0.34	87	87
NCSTN	0.022	0.005	-10000	0	-10000	0	0
ADAM10	0.023	0.002	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.01	0.17	-10000	0	-0.75	23	23
NICD/RBPSUH	0.025	0.067	-10000	0	-10000	0	0
WIF1	-0.32	0.27	0.23	1	-0.53	307	308
NOTCH1	0.01	0.064	-10000	0	-0.4	7	7
PSENEN	0.021	0.007	-10000	0	-10000	0	0
KREMEN2	0.15	0.11	0.23	317	-0.3	6	323
DKK1	0.021	0.089	0.24	21	-0.51	10	31
beta catenin/beta TrCP1	-0.001	0.1	0.28	2	-0.42	12	14
APH1B	0.023	0.002	-10000	0	-10000	0	0
APH1A	0.021	0.006	-10000	0	-10000	0	0
AXIN1	-0.002	0.081	0.26	1	-0.52	8	9
CtBP/CBP/TCF1/TLE1/AES	0.01	0.033	-10000	0	-10000	0	0
PSEN1	0.022	0.005	-10000	0	-10000	0	0
FOS	-0.043	0.18	-10000	0	-0.53	58	58
JUN	0.022	0.004	-10000	0	-10000	0	0
MAP3K7	0.022	0.003	-10000	0	-10000	0	0
CTNNB1	-0.008	0.11	0.26	4	-0.42	15	19
MAPK3	0.022	0.003	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.026	0.19	-10000	0	-0.37	80	80
HNF1A	0.025	0.026	0.23	8	-10000	0	8
CTBP1	0.02	0.006	-10000	0	-10000	0	0
MYC	0.02	0.018	-10000	0	-10000	0	0
NKD1	-0.022	0.15	0.23	4	-0.53	40	44
FZD1	0.021	0.006	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	0.028	0.069	-10000	0	-0.41	1	1
apoptosis	-0.051	0.15	-10000	0	-0.34	87	87
Delta 1/NOTCHprecursor	0.027	0.068	-10000	0	-10000	0	0
DLL1	0.022	0.004	-10000	0	-10000	0	0
PPARD	0.006	0.13	-10000	0	-0.95	9	9
Gamma Secretase	0.055	0.027	-10000	0	-10000	0	0
APC	-0.018	0.11	0.26	1	-0.42	26	27
DVL1	-0.042	0.089	-10000	0	-0.37	21	21
CSNK2A1	0.022	0.005	-10000	0	-10000	0	0
MAP3K7IP1	-0.001	0.001	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	0.11	0.11	0.31	15	-0.36	10	25
LRP6	0.021	0.006	-10000	0	-10000	0	0
CSNK1A1	0.021	0.006	-10000	0	-10000	0	0
NLK	0.009	0.004	-10000	0	-10000	0	0
CCND1	0.004	0.15	-10000	0	-1.4	6	6
WNT1	0.018	0.022	0.23	3	-10000	0	3
Axin1/APC/beta catenin	-0.014	0.13	0.32	4	-0.46	26	30
DKK2	-0.074	0.21	-10000	0	-0.53	86	86
NOTCH1 precursor/DVL1	-0.027	0.11	-10000	0	-0.54	13	13
GSK3B	0.02	0.007	-10000	0	-10000	0	0
FRAT1	0.02	0.025	-10000	0	-0.53	1	1
NOTCH/Deltex homolog 1	0.03	0.069	-10000	0	-0.41	1	1
PPP2R5D	0.015	0.09	0.27	39	-0.41	5	44
MAPK1	0.021	0.006	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.16	0.17	-10000	0	-0.31	279	279
RBPJ	0.021	0.006	-10000	0	-10000	0	0
CREBBP	0.023	0.006	-10000	0	-10000	0	0

×

Glypican 2 network

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.Total.Perturbations
MDK	0.027	0.033	0.26	9	-9999	9
GPC2	0.056	0.085	0.25	73	-9999	73
GPC2/Midkine	0.056	0.06	0.27	12	-9999	12
neuron projection morphogenesis	0.055	0.06	0.27	12	-9999	12

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.028	0.058	0.22	1	-0.29	14	15
RGS9BP	0.011	0.074	-10000	0	-0.53	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
GRK1	-0.004	0.03	0.38	2	-10000	0	2
mol:Na +	0.09	0.07	0.23	9	-0.17	2	11
mol:ADP	-0.003	0.062	0.34	14	-10000	0	14
GNAT2	0.018	0.013	-10000	0	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.003	0.12	-10000	0	-0.34	57	57
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.025	0.008	-10000	0	-10000	0	0
GRK7	0.031	0.066	0.3	26	-10000	0	26
CNGB3	0.12	0.11	0.24	248	-0.3	2	250
Cone Metarhodopsin II/X-Arrestin	0.013	0.002	-10000	0	-10000	0	0
mol:Ca2+	-0.008	0.079	0.21	32	-10000	0	32
Cone PDE6	0.01	0.11	-10000	0	-0.3	53	53
Cone Metarhodopsin II	0.028	0.038	0.22	12	-10000	0	12
Na + (4 Units)	0.11	0.094	0.28	50	-0.2	2	52
GNAT2/GDP	0.007	0.11	-10000	0	-0.3	57	57
GNB5	0.023	0.003	-10000	0	-10000	0	0
mol:GMP (4 units)	-0.005	0.045	0.18	29	-10000	0	29
Cone Transducin	0.03	0.062	0.24	1	-0.3	14	15
SLC24A2	0.054	0.096	0.24	91	-0.3	5	96
GNB3/GNGT2	0.021	0.075	0.27	1	-0.39	14	15
GNB3	0.025	0.03	0.25	8	-10000	0	8
GNAT2/GTP	0.016	0.004	-10000	0	-10000	0	0
CNGA3	0.011	0.027	0.3	2	-10000	0	2
ARR3	-0.01	0.016	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
cGMP/Cone CNG Channel	0.091	0.07	0.24	9	-0.17	2	11
mol:Pi	-0.003	0.12	-10000	0	-0.34	57	57
Cone CNG Channel	0.078	0.063	-10000	0	-10000	0	0
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	0.054	0.096	0.24	91	-0.3	5	96
RGS9	-0.036	0.17	-10000	0	-0.53	52	52
PDE6C	-0.008	0.017	-10000	0	-10000	0	0
GNGT2	0.005	0.098	-10000	0	-0.53	16	16
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	-0.011	0.015	-10000	0	-10000	0	0

×

LPA4-mediated signaling events

Figure S30. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S30. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.028	0.082	-10000	0	-0.34	31	31
ADCY5	-0.033	0.091	-10000	0	-0.34	39	39
ADCY6	-0.01	0.025	-10000	0	-0.33	3	3
ADCY7	-0.008	0.015	-10000	0	-0.33	1	1
ADCY1	-0.009	0.021	-10000	0	-0.33	2	2
ADCY2	-0.009	0.079	0.27	16	-0.33	16	32
ADCY3	-0.008	0.015	-10000	0	-0.33	1	1
ADCY8	-0.093	0.14	0.21	1	-0.33	129	130
PRKCE	-0.006	0.017	-10000	0	-0.39	1	1
ADCY9	-0.009	0.021	-10000	0	-0.33	2	2
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	-0.016	0.12	0.25	31	-0.28	19	50

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.018	0.29	-10000	0	-0.87	32	32
HDAC7	0.023	0.007	-10000	0	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	0.071	0.3	-10000	0	-0.81	18	18
SMAD4	0.021	0.01	-10000	0	-10000	0	0
ID2	-0.008	0.3	0.46	1	-0.88	31	32
AP1	-0.024	0.14	-10000	0	-0.4	58	58
ABCG2	-0.042	0.35	0.46	1	-0.9	47	48
HIF1A	0.013	0.076	-10000	0	-0.38	2	2
TFF3	-0.031	0.33	-10000	0	-0.91	39	39
GATA2	-0.039	0.16	-10000	0	-0.53	49	49
AKT1	0.014	0.069	-10000	0	-0.25	1	1
response to hypoxia	-0.003	0.065	-10000	0	-0.26	9	9
MCL1	-0.014	0.29	0.46	1	-0.88	29	30
NDRG1	-0.007	0.29	0.46	1	-0.88	28	29
SERPINE1	-0.008	0.29	0.46	1	-0.88	29	30
FECH	-0.008	0.3	0.46	1	-0.88	30	31
FURIN	-0.007	0.3	0.46	1	-0.88	30	31
NCOA2	0.022	0.025	-10000	0	-0.53	1	1
EP300	0.015	0.072	-10000	0	-0.28	6	6
HMOX1	-0.007	0.3	0.46	1	-0.88	30	31
BHLHE40	-0.009	0.3	0.46	1	-0.87	31	32
BHLHE41	-0.012	0.3	0.46	1	-0.94	29	30
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.056	0.13	-10000	0	-0.43	9	9
ENG	0.005	0.12	0.35	4	-0.63	9	13
JUN	0.018	0.016	-10000	0	-10000	0	0
RORA	-0.007	0.3	0.46	1	-0.88	31	32
ABCB1	-0.1	0.38	-10000	0	-1.1	59	59
TFRC	-0.029	0.26	-10000	0	-0.86	25	25
CXCR4	-0.007	0.3	0.46	1	-0.88	31	32
TF	-0.012	0.3	0.46	1	-0.87	32	33
CITED2	-0.013	0.31	0.46	1	-0.92	31	32
HIF1A/ARNT	0.12	0.41	0.61	2	-1	29	31
LDHA	0.019	0.13	-10000	0	-0.79	9	9
ETS1	-0.014	0.31	0.46	1	-0.94	31	32
PGK1	-0.009	0.3	0.46	1	-0.88	31	32
NOS2	-0.015	0.33	0.46	1	-0.92	34	35
ITGB2	-0.019	0.32	-10000	0	-0.92	36	36
ALDOA	-0.006	0.3	0.46	1	-0.88	31	32
Cbp/p300/CITED2	0.003	0.32	-10000	0	-0.96	27	27
FOS	-0.047	0.18	-10000	0	-0.54	58	58
HK2	-0.007	0.3	0.46	1	-0.88	31	32
SP1	0.009	0.048	-10000	0	-0.15	8	8
GCK	0.025	0.11	-10000	0	-10000	0	0
HK1	-0.007	0.3	0.46	1	-0.88	31	32
NPM1	-0.009	0.3	0.46	1	-0.87	31	32
EGLN1	-0.008	0.29	0.46	1	-0.88	30	31
CREB1	0.026	0.004	-10000	0	-10000	0	0
PGM1	-0.008	0.3	0.46	1	-0.88	31	32
SMAD3	0.022	0.009	-10000	0	-10000	0	0
EDN1	-0.12	0.38	-10000	0	-1.1	51	51
IGFBP1	-0.008	0.3	0.46	1	-0.87	31	32
VEGFA	0.004	0.23	-10000	0	-0.71	16	16
HIF1A/JAB1	0.025	0.059	-10000	0	-0.27	2	2
CP	-0.026	0.29	0.46	1	-0.93	30	31
CXCL12	-0.029	0.34	0.46	1	-0.99	38	39
COPS5	0.023	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4	0.032	0.015	-10000	0	-10000	0	0
BNIP3	-0.007	0.3	0.46	1	-0.88	31	32
EGLN3	0.001	0.3	0.46	1	-0.88	31	32
CA9	0.054	0.34	0.51	8	-0.92	29	37
TERT	0.031	0.3	0.5	8	-0.87	27	35
ENO1	-0.008	0.3	0.46	1	-0.88	31	32
PFKL	-0.009	0.3	-10000	0	-0.88	31	31
NCOA1	0.023	0.003	-10000	0	-10000	0	0
ADM	-0.008	0.3	0.46	1	-0.88	31	32
ARNT	0.015	0.069	-10000	0	-0.32	1	1
HNF4A	0.027	0.03	0.25	8	-10000	0	8
ADFP	-0.018	0.29	-10000	0	-0.87	32	32
SLC2A1	0.051	0.27	0.4	6	-0.69	26	32
LEP	0.006	0.31	0.46	1	-0.88	30	31
HIF1A/ARNT/Cbp/p300	0.065	0.3	-10000	0	-0.79	24	24
EPO	0.035	0.19	-10000	0	-0.75	4	4
CREBBP	0.013	0.076	-10000	0	-0.29	9	9
HIF1A/ARNT/Cbp/p300/HDAC7	0.099	0.32	-10000	0	-0.81	20	20
PFKFB3	-0.008	0.3	0.46	1	-0.87	31	32
NT5E	-0.008	0.3	0.46	1	-0.89	31	32

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	0.031	0.03	0.27	1	-0.39	2	3
CRKL	-0.048	0.18	0.31	3	-0.6	31	34
mol:PIP3	0.012	0.019	-10000	0	-10000	0	0
AKT1	0.011	0.042	-10000	0	-10000	0	0
PTK2B	0.021	0.007	-10000	0	-10000	0	0
RAPGEF1	-0.046	0.17	0.42	2	-0.57	31	33
RANBP10	0.022	0.005	-10000	0	-10000	0	0
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
HGF/MET/SHIP2	-0.033	0.15	0.25	1	-0.34	95	96
MAP3K5	-0.042	0.16	0.34	2	-0.54	34	36
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.021	0.15	0.25	1	-0.31	97	98
AP1	-0.026	0.12	-10000	0	-0.34	58	58
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.022	0.005	-10000	0	-10000	0	0
apoptosis	-0.11	0.3	-10000	0	-0.78	80	80
STAT3 (dimer)	-0.042	0.12	-10000	0	-0.34	21	21
GAB1/CRKL/SHP2/PI3K	-0.02	0.14	-10000	0	-0.53	22	22
INPP5D	0.021	0.025	-10000	0	-0.53	1	1
CBL/CRK	-0.045	0.17	-10000	0	-0.58	31	31
PTPN11	0.023	0.002	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.022	0.004	-10000	0	-10000	0	0
PTEN	0.02	0.007	-10000	0	-10000	0	0
ELK1	-0.004	0.075	0.3	19	-10000	0	19
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.029	0.087	-10000	0	-0.31	21	21
PAK1	0.012	0.048	0.39	1	-10000	0	1
HGF/MET/RANBP10	-0.033	0.15	0.25	1	-0.33	98	99
HRAS	-0.056	0.16	-10000	0	-0.6	14	14
DOCK1	-0.047	0.16	0.4	1	-0.57	31	32
GAB1	-0.057	0.18	-10000	0	-0.65	30	30
CRK	-0.056	0.17	-10000	0	-0.62	30	30
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.09	0.21	-10000	0	-0.5	99	99
JUN	0.022	0.004	-10000	0	-10000	0	0
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.035	0.089	0.18	1	-0.21	99	100
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
cell morphogenesis	0.018	0.16	0.33	19	-0.43	15	34
GRB2/SHC	-0.009	0.09	-10000	0	-0.28	8	8
FOS	-0.043	0.18	-10000	0	-0.53	58	58
GLMN	0.003	0.001	-10000	0	-10000	0	0
cell motility	-0.004	0.075	0.3	19	-10000	0	19
HGF/MET/MUC20	-0.044	0.14	0.24	1	-0.33	99	100
cell migration	-0.009	0.088	-10000	0	-0.28	8	8
GRB2	0.022	0.004	-10000	0	-10000	0	0
CBL	0.022	0.004	-10000	0	-10000	0	0
MET/RANBP10	0.03	0.03	0.27	1	-0.39	2	3
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.036	0.11	-10000	0	-0.27	87	87
MET/MUC20	0.015	0.028	0.25	1	-0.39	2	3
RAP1B	-0.039	0.16	0.37	4	-0.53	31	35
RAP1A	-0.046	0.16	0.35	3	-0.53	31	34
HGF/MET/RANBP9	-0.033	0.15	0.25	1	-0.34	98	99
RAF1	-0.052	0.15	-10000	0	-0.58	13	13
STAT3	-0.042	0.12	-10000	0	-0.35	21	21
cell proliferation	-0.057	0.16	0.25	4	-0.36	82	86
RPS6KB1	-0.007	0.043	-10000	0	-0.3	3	3
MAPK3	-0.005	0.1	0.74	7	-10000	0	7
MAPK1	-0.002	0.11	0.68	9	-10000	0	9
RANBP9	0.022	0.004	-10000	0	-10000	0	0
MAPK8	-0.023	0.15	0.34	3	-0.49	32	35
SRC	-0.043	0.1	-10000	0	-0.33	16	16
PI3K	-0.001	0.064	-10000	0	-0.26	6	6
MET/Glomulin	0.013	0.033	0.27	1	-0.34	2	3
SOS1	0.022	0.004	-10000	0	-10000	0	0
MAP2K1	-0.051	0.14	-10000	0	-0.53	13	13
MET	0.02	0.039	0.38	1	-0.53	2	3
MAP4K1	-0.044	0.18	0.35	2	-0.58	35	37
PTK2	0.021	0.006	-10000	0	-10000	0	0
MAP2K2	-0.05	0.14	-10000	0	-0.53	13	13
BAD	0.01	0.041	-10000	0	-10000	0	0
MAP2K4	-0.039	0.15	0.32	2	-0.49	32	34
SHP2/GRB2/SOS1/GAB1	-0.032	0.16	-10000	0	-0.54	30	30
INPPL1	0.022	0.005	-10000	0	-10000	0	0
PXN	0.023	0.002	-10000	0	-10000	0	0
SH3KBP1	0.02	0.035	-10000	0	-0.53	2	2
HGS	-0.036	0.082	0.16	1	-0.2	93	94
PLCgamma1/PKC	0.016	0.003	-10000	0	-10000	0	0
HGF	-0.09	0.22	-10000	0	-0.53	100	100
RASA1	0.021	0.006	-10000	0	-10000	0	0
NCK1	0.019	0.008	-10000	0	-10000	0	0
PTPRJ	0.021	0.025	-10000	0	-0.53	1	1
NCK/PLCgamma1	-0.011	0.091	-10000	0	-0.26	4	4
PDPK1	0.008	0.021	-10000	0	-10000	0	0
HGF/MET/SHIP	-0.034	0.15	0.25	1	-0.34	99	100

×

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	0.009	0.12	-10000	0	-0.4	23	23
TBX21	-0.12	0.46	-10000	0	-1.3	58	58
B2M	0.021	0.011	-10000	0	-10000	0	0
TYK2	0.014	0.031	-10000	0	-10000	0	0
IL12RB1	-0.017	0.14	-10000	0	-0.56	29	29
GADD45B	-0.063	0.35	-10000	0	-1.1	40	40
IL12RB2	0.036	0.074	0.24	45	-0.29	1	46
GADD45G	-0.048	0.32	-10000	0	-1	33	33
natural killer cell activation	0	0.017	0.042	4	-0.042	33	37
RELB	0.023	0.016	0.38	1	-10000	0	1
RELA	0.023	0.002	-10000	0	-10000	0	0
IL18	0.016	0.047	-10000	0	-0.55	3	3
IL2RA	0.021	0.039	0.23	3	-0.53	2	5
IFNG	0.016	0.052	0.23	2	-0.53	4	6
STAT3 (dimer)	-0.047	0.28	-10000	0	-0.76	50	50
HLA-DRB5	-0.002	0.007	-10000	0	-0.023	49	49
FASLG	-0.078	0.39	-10000	0	-1.2	43	43
NF kappa B2 p52/RelB	-0.057	0.34	-10000	0	-0.93	48	48
CD4	0	0.092	-10000	0	-0.53	14	14
SOCS1	0.021	0.025	-10000	0	-0.53	1	1
EntrezGene:6955	-0.002	0.01	-10000	0	-0.028	59	59
CD3D	0.006	0.076	-10000	0	-0.54	9	9
CD3E	0.007	0.072	-10000	0	-0.54	8	8
CD3G	-0.017	0.13	-10000	0	-0.54	30	30
IL12Rbeta2/JAK2	0.034	0.065	-10000	0	-10000	0	0
CCL3	-0.067	0.34	-10000	0	-1	38	38
CCL4	-0.07	0.35	-10000	0	-1.1	39	39
HLA-A	0	0.006	-10000	0	-0.042	8	8
IL18/IL18R	0.031	0.11	-10000	0	-0.41	24	24
NOS2	-0.093	0.41	-10000	0	-1.2	52	52
IL12/IL12R/TYK2/JAK2/SPHK2	0.01	0.12	-10000	0	-0.39	23	23
IL1R1	-0.064	0.33	-10000	0	-1	40	40
IL4	-0.007	0.031	-10000	0	-10000	0	0
JAK2	0.013	0.029	-10000	0	-10000	0	0
EntrezGene:6957	-0.002	0.009	-10000	0	-0.025	56	56
TCR/CD3/MHC I/CD8	-0.047	0.26	-10000	0	-1	26	26
RAB7A	-0.019	0.28	0.49	2	-0.8	37	39
lysosomal transport	-0.015	0.27	0.49	2	-0.75	37	39
FOS	-0.16	0.46	-10000	0	-1.1	84	84
STAT4 (dimer)	-0.051	0.33	0.44	2	-0.91	47	49
STAT5A (dimer)	-0.061	0.34	-10000	0	-0.93	49	49
GZMA	-0.071	0.35	-10000	0	-1.1	38	38
GZMB	-0.07	0.36	-10000	0	-1.1	36	36
HLX	0.022	0.004	-10000	0	-10000	0	0
LCK	-0.074	0.36	-10000	0	-1	48	48
TCR/CD3/MHC II/CD4	-0.039	0.17	-10000	0	-0.36	70	70
IL2/IL2R	0.044	0.067	-10000	0	-0.42	8	8
MAPK14	-0.054	0.34	-10000	0	-1	42	42
CCR5	-0.071	0.36	-10000	0	-1.2	36	36
IL1B	0.002	0.09	-10000	0	-0.56	11	11
STAT6	0.006	0.091	-10000	0	-10000	0	0
STAT4	0.013	0.07	-10000	0	-0.53	8	8
STAT3	0.022	0.003	-10000	0	-10000	0	0
STAT1	0.022	0.004	-10000	0	-10000	0	0
NFKB1	0.022	0.005	-10000	0	-10000	0	0
NFKB2	0.022	0.005	-10000	0	-10000	0	0
IL12B	0.013	0.03	-10000	0	-10000	0	0
CD8A	0.014	0.067	-10000	0	-0.54	7	7
CD8B	0.009	0.092	0.23	4	-0.54	13	17
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.008	0.12	0.4	23	-10000	0	23
IL2RB	0.019	0.043	-10000	0	-0.53	3	3
proteasomal ubiquitin-dependent protein catabolic process	-0.04	0.29	0.44	2	-0.81	47	49
IL2RG	0.015	0.065	-10000	0	-0.53	7	7
IL12	0.013	0.058	-10000	0	-0.4	6	6
STAT5A	0.022	0.003	-10000	0	-10000	0	0
CD247	0.002	0.087	-10000	0	-0.54	12	12
IL2	0.001	0.02	-10000	0	-10000	0	0
SPHK2	0.022	0.004	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.004	0.066	-10000	0	-0.54	6	6
IL12/IL12R/TYK2/JAK2	-0.091	0.4	-10000	0	-1.1	51	51
MAP2K3	-0.061	0.35	-10000	0	-1	43	43
RIPK2	0.022	0.005	-10000	0	-10000	0	0
MAP2K6	-0.052	0.33	-10000	0	-0.99	41	41
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.002	0.008	-10000	0	-0.026	54	54
IL18RAP	-0.004	0.11	-10000	0	-0.54	21	21
IL12Rbeta1/TYK2	-0.002	0.11	-10000	0	-0.43	29	29
EOMES	-0.062	0.26	-10000	0	-0.93	30	30
STAT1 (dimer)	-0.043	0.28	-10000	0	-0.77	45	45
T cell proliferation	-0.026	0.24	0.43	2	-0.65	44	46
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.014	0.059	-10000	0	-0.54	5	5
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.046	0.26	-10000	0	-0.75	40	40
ATF2	-0.045	0.31	0.44	1	-0.92	40	41

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	0.012	0.16	0.31	12	-0.53	29	41
FYN	-0.015	0.21	0.29	14	-0.68	34	48
LAT/GRAP2/SLP76	-0.01	0.18	0.26	4	-0.56	35	39
IKBKB	0.021	0.017	0.38	1	-10000	0	1
AKT1	-0.008	0.14	0.27	10	-0.42	39	49
B2M	0.021	0.012	-10000	0	-10000	0	0
IKBKG	0.001	0.043	0.1	7	-0.14	16	23
MAP3K8	0.021	0.025	-10000	0	-0.53	1	1
mol:Ca2+	-0.013	0.015	0.087	1	-0.082	7	8
integrin-mediated signaling pathway	0.029	0.007	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.021	0.21	0.32	9	-0.62	40	49
TRPV6	0.007	0.17	1.1	9	-0.55	8	17
CD28	0.018	0.05	-10000	0	-0.54	4	4
SHC1	-0.015	0.2	0.3	16	-0.68	30	46
receptor internalization	-0.026	0.21	0.23	4	-0.68	38	42
PRF1	-0.061	0.32	-10000	0	-1	43	43
KRAS	0.021	0.006	-10000	0	-10000	0	0
GRB2	0.022	0.004	-10000	0	-10000	0	0
COT/AKT1	0.006	0.12	0.26	9	-0.34	35	44
LAT	-0.018	0.19	0.28	6	-0.69	29	35
EntrezGene:6955	0	0.004	-10000	0	-10000	0	0
CD3D	0.012	0.076	-10000	0	-0.55	9	9
CD3E	0.012	0.072	-10000	0	-0.55	8	8
CD3G	-0.012	0.13	-10000	0	-0.54	30	30
RASGRP2	-0.018	0.061	-10000	0	-0.17	66	66
RASGRP1	-0.009	0.14	0.27	10	-0.43	34	44
HLA-A	0	0.005	-10000	0	-10000	0	0
RASSF5	0.022	0.004	-10000	0	-10000	0	0
RAP1A/GTP/RAPL	0.029	0.007	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.011	0.058	0.15	25	-0.13	21	46
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.015	0.06	-10000	0	-0.24	23	23
PRKCA	-0.003	0.085	0.16	12	-0.28	27	39
GRAP2	-0.008	0.13	-10000	0	-0.53	27	27
mol:IP3	-0.017	0.12	0.23	4	-0.42	32	36
EntrezGene:6957	0	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.026	0.18	-10000	0	-0.7	27	27
ORAI1	-0.013	0.13	0.62	1	-0.96	8	9
CSK	-0.018	0.2	0.28	6	-0.7	29	35
B7 family/CD28	-0.012	0.22	-10000	0	-0.76	32	32
CHUK	0.022	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.037	0.22	0.24	1	-0.67	41	42
PTPN6	-0.025	0.19	0.25	3	-0.7	29	32
VAV1	-0.021	0.2	0.3	5	-0.71	29	34
Monovalent TCR/CD3	-0.021	0.16	-10000	0	-0.48	38	38
CBL	0.022	0.004	-10000	0	-10000	0	0
LCK	-0.016	0.21	0.3	12	-0.69	33	45
PAG1	-0.016	0.2	0.27	11	-0.7	29	40
RAP1A	0.022	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.034	0.22	0.29	4	-0.75	34	38
CD80	0.002	0.099	-10000	0	-0.54	16	16
CD86	0.015	0.056	-10000	0	-0.54	5	5
PDK1/CARD11/BCL10/MALT1	-0.009	0.075	-10000	0	-0.28	24	24
HRAS	0.022	0.004	-10000	0	-10000	0	0
GO:0035030	-0.029	0.17	-10000	0	-0.57	35	35
CD8A	0.014	0.067	-10000	0	-0.54	7	7
CD8B	0.008	0.093	0.23	4	-0.54	13	17
PTPRC	-0.012	0.14	-10000	0	-0.54	31	31
PDK1/PKC theta	-0.021	0.17	0.28	9	-0.52	38	47
CSK/PAG1	-0.016	0.19	0.27	11	-0.67	28	39
SOS1	0.022	0.004	-10000	0	-10000	0	0
peptide-MHC class I	0.015	0.017	-10000	0	-0.15	3	3
GRAP2/SLP76	-0.012	0.21	0.3	2	-0.66	36	38
STIM1	-0.004	0.078	1.3	1	-0.93	1	2
RAS family/GTP	0.019	0.071	0.19	22	-0.19	18	40
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.03	0.23	0.23	4	-0.74	38	42
mol:DAG	-0.027	0.1	-10000	0	-0.37	33	33
RAP1A/GDP	0.008	0.028	0.088	15	-0.066	9	24
PLCG1	0.022	0.004	-10000	0	-10000	0	0
CD247	0.008	0.087	-10000	0	-0.54	12	12
cytotoxic T cell degranulation	-0.055	0.3	-10000	0	-0.96	43	43
RAP1A/GTP	-0.006	0.023	-10000	0	-0.064	66	66
mol:PI-3-4-5-P3	-0.012	0.17	0.28	12	-0.5	40	52
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.015	0.16	0.25	4	-0.55	32	36
NRAS	0.022	0.005	-10000	0	-10000	0	0
ZAP70	0.013	0.07	-10000	0	-0.53	8	8
GRB2/SOS1	0.032	0.008	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.019	0.16	-10000	0	-0.55	33	33
MALT1	0.022	0.005	-10000	0	-10000	0	0
TRAF6	0.022	0.004	-10000	0	-10000	0	0
CD8 heterodimer	0.017	0.098	-10000	0	-0.51	15	15
CARD11	0.022	0.031	0.3	2	-0.53	1	3
PRKCB	-0.01	0.099	0.16	12	-0.31	36	48
PRKCE	-0.006	0.081	0.16	7	-0.28	25	32
PRKCQ	-0.027	0.2	0.29	9	-0.59	40	49
LCP2	0.015	0.056	-10000	0	-0.53	5	5
BCL10	0.022	0.004	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.004	0.12	0.23	15	-0.36	37	52
IKK complex	0.011	0.054	0.14	30	-0.12	17	47
RAS family/GDP	-0.002	0.01	-10000	0	-10000	0	0
MAP3K14	0.002	0.091	0.18	14	-0.28	29	43
PDPK1	-0.007	0.14	0.27	10	-0.41	35	45
TCR/CD3/MHC I/CD8/Fyn	-0.032	0.22	-10000	0	-0.81	29	29

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.11	0.42	-10000	0	-1.3	34	34
IL23A	-0.085	0.39	-10000	0	-1.3	26	26
NF kappa B1 p50/RelA/I kappa B alpha	-0.074	0.4	-10000	0	-1.1	37	37
positive regulation of T cell mediated cytotoxicity	-0.11	0.45	-10000	0	-1.3	41	41
ITGA3	-0.094	0.39	-10000	0	-1.2	32	32
IL17F	-0.006	0.28	-10000	0	-0.73	28	28
IL12B	0.019	0.04	-10000	0	-10000	0	0
STAT1 (dimer)	-0.1	0.42	-10000	0	-1.2	39	39
CD4	-0.093	0.42	-10000	0	-1.3	34	34
IL23	-0.076	0.38	-10000	0	-1.2	26	26
IL23R	-0.002	0.17	-10000	0	-0.92	12	12
IL1B	-0.095	0.41	-10000	0	-1.3	28	28
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.088	0.38	-10000	0	-1.1	31	31
TYK2	0.016	0.033	-10000	0	-10000	0	0
STAT4	0.013	0.07	-10000	0	-0.53	8	8
STAT3	0.022	0.003	-10000	0	-10000	0	0
IL18RAP	-0.001	0.11	-10000	0	-0.53	21	21
IL12RB1	-0.016	0.14	-10000	0	-0.56	29	29
PIK3CA	0.013	0.011	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	-0.001	0.11	-10000	0	-0.42	29	29
IL23R/JAK2	0.013	0.16	-10000	0	-0.92	9	9
positive regulation of chronic inflammatory response	-0.11	0.45	-10000	0	-1.3	41	41
natural killer cell activation	0	0.006	-10000	0	-10000	0	0
JAK2	0.019	0.039	-10000	0	-10000	0	0
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
NFKB1	0.02	0.012	-10000	0	-10000	0	0
RELA	0.021	0.011	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.07	0.36	-10000	0	-1.1	26	26
ALOX12B	-0.086	0.38	-10000	0	-1.2	27	27
CXCL1	-0.11	0.44	-10000	0	-1.3	42	42
T cell proliferation	-0.11	0.45	-10000	0	-1.3	41	41
NFKBIA	0.02	0.012	-10000	0	-10000	0	0
IL17A	0.003	0.23	-10000	0	-0.59	19	19
PI3K	-0.1	0.37	-10000	0	-1.2	32	32
IFNG	-0.001	0.035	0.1	3	-0.11	25	28
STAT3 (dimer)	-0.092	0.36	-10000	0	-1.1	32	32
IL18R1	0.017	0.055	-10000	0	-0.53	5	5
IL23/IL23R/JAK2/TYK2/SOCS3	-0.062	0.31	-10000	0	-0.87	39	39
IL18/IL18R	0.025	0.095	-10000	0	-0.38	24	24
macrophage activation	-0.005	0.018	0.029	1	-0.045	21	22
TNF	-0.099	0.42	-10000	0	-1.3	32	32
STAT3/STAT4	-0.093	0.41	-10000	0	-1.2	39	39
STAT4 (dimer)	-0.1	0.43	-10000	0	-1.2	40	40
IL18	0.019	0.043	-10000	0	-0.53	3	3
IL19	-0.089	0.38	-10000	0	-1.2	26	26
STAT5A (dimer)	-0.1	0.43	-10000	0	-1.2	40	40
STAT1	0.022	0.004	-10000	0	-10000	0	0
SOCS3	0.02	0.035	-10000	0	-0.53	2	2
CXCL9	-0.11	0.41	-10000	0	-1.2	39	39
MPO	-0.12	0.44	-10000	0	-1.2	45	45
positive regulation of humoral immune response	-0.11	0.45	-10000	0	-1.3	41	41
IL23/IL23R/JAK2/TYK2	-0.12	0.5	-10000	0	-1.4	40	40
IL6	-0.2	0.55	-10000	0	-1.3	90	90
STAT5A	0.022	0.003	-10000	0	-10000	0	0
IL2	0.008	0.021	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0	0.006	-10000	0	-10000	0	0
CD3E	-0.098	0.4	-10000	0	-1.3	26	26
keratinocyte proliferation	-0.11	0.45	-10000	0	-1.3	41	41
NOS2	-0.12	0.45	-10000	0	-1.3	47	47

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.029	0.085	-10000	0	-0.32	25	25
ER alpha/Gai/GDP/Gbeta gamma	-0.037	0.18	-10000	0	-0.54	44	44
AKT1	-0.027	0.2	-10000	0	-0.77	30	30
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.023	0.2	-10000	0	-0.78	30	30
mol:Ca2+	-0.097	0.18	-10000	0	-0.41	114	114
IGF1R	0.022	0.004	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	0.013	0.075	-10000	0	-0.33	22	22
SHC1	0.022	0.005	-10000	0	-10000	0	0
apoptosis	0.025	0.18	0.73	30	-10000	0	30
RhoA/GTP	0.006	0.057	-10000	0	-0.26	20	20
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.009	0.15	-10000	0	-0.46	40	40
regulation of stress fiber formation	0.01	0.069	0.43	2	-0.22	3	5
E2/ERA-ERB (dimer)	0.013	0.075	-10000	0	-0.33	22	22
KRAS	0.021	0.006	-10000	0	-10000	0	0
G13/GTP	0.014	0.067	-10000	0	-0.3	21	21
pseudopodium formation	-0.01	0.069	0.22	3	-0.43	2	5
E2/ER alpha (dimer)/PELP1	0.012	0.076	-10000	0	-0.33	23	23
GRB2	0.022	0.004	-10000	0	-10000	0	0
GNG2	0.016	0.055	-10000	0	-0.53	5	5
GNAO1	0.021	0.029	0.23	2	-0.53	1	3
HRAS	0.022	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.027	0.17	-10000	0	-0.53	40	40
E2/ER beta (dimer)	0.016	0.003	-10000	0	-10000	0	0
mol:GDP	-0.005	0.086	-10000	0	-0.38	23	23
mol:NADP	-0.027	0.17	-10000	0	-0.53	40	40
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
mol:IP3	-0.1	0.19	-10000	0	-0.43	114	114
IGF-1R heterotetramer	0.022	0.004	-10000	0	-10000	0	0
PLCB1	-0.095	0.19	-10000	0	-0.44	112	112
PLCB2	-0.1	0.2	-10000	0	-0.44	120	120
IGF1	0.003	0.1	0.23	1	-0.53	18	19
mol:L-citrulline	-0.027	0.17	-10000	0	-0.53	40	40
RHOA	0.021	0.007	-10000	0	-10000	0	0
Gai/GDP	-0.038	0.2	-10000	0	-0.62	53	53
JNK cascade	0.016	0.003	-10000	0	-10000	0	0
BCAR1	0.022	0.005	-10000	0	-10000	0	0
ESR2	0.022	0.005	-10000	0	-10000	0	0
GNAQ	0.021	0.025	-10000	0	-0.53	1	1
ESR1	-0.003	0.12	-10000	0	-0.53	23	23
Gq family/GDP/Gbeta gamma	-0.069	0.2	-10000	0	-0.67	34	34
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.014	0.073	-10000	0	-0.47	3	3
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.008	0.15	-10000	0	-0.46	39	39
GNAZ	0.016	0.056	-10000	0	-0.53	5	5
E2/ER alpha (dimer)	-0.002	0.085	-10000	0	-0.38	24	24
STRN	0.022	0.003	-10000	0	-10000	0	0
GNAL	0.02	0.035	-10000	0	-0.53	2	2
PELP1	0.022	0.005	-10000	0	-10000	0	0
MAPK11	0.01	0.003	-10000	0	-10000	0	0
GNAI2	0.021	0.007	-10000	0	-10000	0	0
GNAI3	0.022	0.005	-10000	0	-10000	0	0
GNAI1	0.021	0.025	-10000	0	-0.53	1	1
HBEGF	-0.037	0.18	0.3	7	-0.59	35	42
cAMP biosynthetic process	0.01	0.063	-10000	0	-0.28	20	20
SRC	-0.034	0.17	0.26	2	-0.51	43	45
PI3K	0.017	0.017	-10000	0	-10000	0	0
GNB1	0.021	0.025	-10000	0	-0.53	1	1
G13/GDP/Gbeta gamma	0.015	0.095	-10000	0	-0.41	19	19
SOS1	0.022	0.004	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.027	0.12	-10000	0	-0.4	37	37
Gs family/GTP	0.016	0.065	-10000	0	-0.29	20	20
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.037	0.016	-10000	0	-10000	0	0
vasodilation	-0.025	0.16	-10000	0	-0.5	40	40
mol:DAG	-0.1	0.19	-10000	0	-0.43	114	114
Gs family/GDP/Gbeta gamma	0	0.087	-10000	0	-0.4	18	18
MSN	-0.011	0.073	0.23	3	-0.46	2	5
Gq family/GTP	-0.095	0.21	-10000	0	-0.45	122	122
mol:PI-3-4-5-P3	-0.021	0.19	-10000	0	-0.75	30	30
NRAS	0.022	0.005	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.025	0.16	0.5	40	-10000	0	40
GRB2/SOS1	0.032	0.008	-10000	0	-10000	0	0
RhoA/GDP	0.007	0.087	-10000	0	-0.39	19	19
NOS3	-0.03	0.18	-10000	0	-0.57	40	40
GNA11	0.022	0.004	-10000	0	-10000	0	0
MAPKKK cascade	-0.01	0.16	0.32	1	-0.61	28	29
E2/ER alpha (dimer)/PELP1/Src	-0.015	0.16	-10000	0	-0.48	42	42
ruffle organization	-0.01	0.069	0.22	3	-0.43	2	5
ROCK2	-0.008	0.074	0.24	3	-10000	0	3
GNA14	-0.11	0.24	-10000	0	-0.53	117	117
GNA15	0.022	0.004	-10000	0	-10000	0	0
GNA13	0.022	0.003	-10000	0	-10000	0	0
MMP9	-0.028	0.16	0.32	8	-0.49	40	48
MMP2	-0.029	0.17	0.29	4	-0.57	29	33

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.16	0.26	-10000	0	-0.53	162	162
oxygen homeostasis	0	0	-10000	0	-10000	0	0
TCEB2	0.022	0.004	-10000	0	-10000	0	0
TCEB1	0.022	0.005	-10000	0	-10000	0	0
HIF1A/p53	0.012	0.067	0.25	2	-0.28	17	19
HIF1A	-0.004	0.048	-10000	0	-0.27	15	15
COPS5	0.022	0.004	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.058	0.024	-10000	0	-10000	0	0
FIH (dimer)	0.022	0.005	-10000	0	-10000	0	0
CDKN2A	0.091	0.14	0.23	207	-0.31	20	227
ARNT/IPAS	-0.1	0.19	-10000	0	-0.39	147	147
HIF1AN	0.022	0.005	-10000	0	-10000	0	0
GNB2L1	0.021	0.006	-10000	0	-10000	0	0
HIF1A/ARNT	0.01	0.063	-10000	0	-0.28	19	19
CUL2	0.022	0.004	-10000	0	-10000	0	0
OS9	0.023	0.002	-10000	0	-10000	0	0
RACK1/Elongin B/Elongin C	0.041	0.015	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF1A/Hsp90	0.012	0.064	0.26	1	-0.28	20	21
PHD1-3/OS9	0.068	0.051	0.25	2	-10000	0	2
HIF1A/RACK1/Elongin B/Elongin C	0.031	0.061	-10000	0	-0.28	5	5
VHL	0.021	0.006	-10000	0	-10000	0	0
HSP90AA1	0.022	0.005	-10000	0	-10000	0	0
HIF1A/JAB1	0.013	0.062	0.25	2	-0.28	16	18
EGLN3	0.054	0.077	0.23	76	-10000	0	76
EGLN2	0.021	0.006	-10000	0	-10000	0	0
EGLN1	0.022	0.004	-10000	0	-10000	0	0
TP53	0.02	0.025	-10000	0	-0.53	1	1
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	-0.014	0.17	-10000	0	-0.58	38	38
ARNT	0.021	0.006	-10000	0	-10000	0	0
ARD1A	0	0	-10000	0	-10000	0	0
RBX1	0.022	0.004	-10000	0	-10000	0	0
HIF1A/p19ARF	0.053	0.11	0.28	9	-0.33	20	29

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	-0.01	0.003	-10000	0	-10000	0	0
SMARCC1	0.004	0.022	-10000	0	-10000	0	0
REL	0.021	0.007	-10000	0	-10000	0	0
HDAC7	-0.067	0.11	-10000	0	-0.32	13	13
JUN	0.022	0.004	-10000	0	-10000	0	0
EP300	0.022	0.004	-10000	0	-10000	0	0
KAT2B	0.021	0.006	-10000	0	-10000	0	0
KAT5	0.023	0.002	-10000	0	-10000	0	0
MAPK14	-0.009	0.023	-10000	0	-10000	0	0
FOXO1	0.021	0.006	-10000	0	-10000	0	0
T-DHT/AR	-0.054	0.12	-10000	0	-0.31	38	38
MAP2K6	0.007	0.026	0.22	1	-10000	0	1
BRM/BAF57	0.029	0.022	-10000	0	-0.39	1	1
MAP2K4	0.007	0.024	-10000	0	-10000	0	0
SMARCA2	0.019	0.026	-10000	0	-0.53	1	1
PDE9A	-0.082	0.22	-10000	0	-0.94	20	20
NCOA2	0.021	0.025	-10000	0	-0.53	1	1
CEBPA	0.02	0.026	-10000	0	-0.53	1	1
EHMT2	0.022	0.004	-10000	0	-10000	0	0
cell proliferation	-0.078	0.16	0.33	4	-0.43	46	50
NR0B1	0.07	0.12	0.23	152	-0.3	7	159
EGR1	0.011	0.074	-10000	0	-0.53	9	9
RXRs/9cRA	-0.13	0.17	-10000	0	-0.31	241	241
AR/RACK1/Src	-0.025	0.077	0.3	3	-0.28	1	4
AR/GR	-0.043	0.12	-10000	0	-0.28	91	91
GNB2L1	0.021	0.006	-10000	0	-10000	0	0
PKN1	0.022	0.004	-10000	0	-10000	0	0
RCHY1	0.022	0.005	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
MAPK8	-0.009	0.022	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.018	0.081	0.27	1	-0.32	2	3
SRC	-0.027	0.036	0.2	3	-10000	0	3
NR3C1	0.021	0.006	-10000	0	-10000	0	0
KLK3	-0.04	0.13	-10000	0	-0.52	3	3
APPBP2	0.007	0.024	-10000	0	-10000	0	0
TRIM24	0.022	0.004	-10000	0	-10000	0	0
T-DHT/AR/TIP60	-0.031	0.074	-10000	0	-0.29	1	1
TMPRSS2	-0.35	0.51	-10000	0	-1.1	165	165
RXRG	-0.25	0.27	-10000	0	-0.53	244	244
mol:9cRA	0	0	-10000	0	-10000	0	0
RXRA	0.022	0.004	-10000	0	-10000	0	0
RXRB	0.022	0.004	-10000	0	-10000	0	0
CARM1	0.022	0.004	-10000	0	-10000	0	0
NR2C2	0.021	0.006	-10000	0	-10000	0	0
KLK2	-0.013	0.074	0.34	2	-0.35	2	4
AR	-0.06	0.12	-10000	0	-0.3	87	87
SENP1	0.023	0.003	-10000	0	-10000	0	0
HSP90AA1	0.022	0.005	-10000	0	-10000	0	0
MDM2	0.023	0.016	0.38	1	-10000	0	1
SRY	0	0	-10000	0	-10000	0	0
GATA2	-0.034	0.16	-10000	0	-0.53	49	49
MYST2	0	0	-10000	0	-10000	0	0
HOXB13	0.14	0.11	0.23	293	-10000	0	293
T-DHT/AR/RACK1/Src	-0.025	0.077	0.3	3	-0.28	1	4
positive regulation of transcription	-0.034	0.16	-10000	0	-0.53	49	49
DNAJA1	0.007	0.023	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.012	0.01	0.22	1	-10000	0	1
NCOA1	0.031	0.02	-10000	0	-10000	0	0
SPDEF	-0.044	0.18	0.23	4	-0.53	61	65
T-DHT/AR/TIF2	-0.022	0.081	-10000	0	-0.36	13	13
T-DHT/AR/Hsp90	-0.029	0.073	0.22	1	-0.29	1	2
GSK3B	0.016	0.013	-10000	0	-10000	0	0
NR2C1	0.023	0.002	-10000	0	-10000	0	0
mol:T-DHT	-0.029	0.034	-10000	0	-10000	0	0
SIRT1	0.022	0.005	-10000	0	-10000	0	0
ZMIZ2	0.022	0.005	-10000	0	-10000	0	0
POU2F1	-0.011	0.061	-10000	0	-0.18	5	5
T-DHT/AR/DAX-1	-0.018	0.11	0.28	4	-0.3	2	6
CREBBP	0.022	0.005	-10000	0	-10000	0	0
SMARCE1	0.022	0.004	-10000	0	-10000	0	0

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	-0.006	0.092	-10000	0	-0.43	4	4
SMARCC2	0.023	0.002	-10000	0	-10000	0	0
SMARCC1	0.021	0.007	-10000	0	-10000	0	0
TBX21	-0.071	0.29	0.45	3	-0.87	50	53
SUMO2	0.021	0.008	-10000	0	-10000	0	0
STAT1 (dimer)	0.026	0.005	-10000	0	-10000	0	0
FKBP4	0.022	0.017	0.38	1	-10000	0	1
FKBP5	0.022	0.003	-10000	0	-10000	0	0
GR alpha/HSP90/FKBP51/HSP90	0.013	0.11	0.29	14	-10000	0	14
PRL	0.011	0.09	0.41	1	-10000	0	1
cortisol/GR alpha (dimer)/TIF2	0.011	0.25	0.51	46	-0.39	38	84
RELA	-0.061	0.13	-10000	0	-0.3	51	51
FGG	-0.22	0.33	0.47	13	-0.57	206	219
GR beta/TIF2	0.005	0.12	0.3	21	-0.3	1	22
IFNG	0.015	0.19	-10000	0	-0.81	10	10
apoptosis	-0.005	0.11	0.5	3	-0.52	5	8
CREB1	0.026	0.01	-10000	0	-10000	0	0
histone acetylation	-0.002	0.11	0.32	1	-0.35	14	15
BGLAP	0.016	0.11	-10000	0	-0.48	1	1
GR/PKAc	0.013	0.11	0.31	8	-10000	0	8
NF kappa B1 p50/RelA	-0.12	0.24	-10000	0	-0.4	167	167
SMARCD1	0.023	0.002	-10000	0	-10000	0	0
MDM2	0.006	0.079	0.23	22	-10000	0	22
GATA3	0.012	0.091	0.23	3	-0.53	13	16
AKT1	0.019	0.005	-10000	0	-10000	0	0
CSF2	-0.12	0.35	-10000	0	-1.2	49	49
GSK3B	0.019	0.01	-10000	0	-10000	0	0
NR1I3	0.003	0.11	0.56	3	-0.62	1	4
CSN2	-0.04	0.17	0.37	17	-0.35	41	58
BRG1/BAF155/BAF170/BAF60A	0.055	0.02	-10000	0	-10000	0	0
NFATC1	0.021	0.025	-10000	0	-0.53	1	1
POU2F1	0.023	0.007	-10000	0	-10000	0	0
CDKN1A	0.008	0.045	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0	0.004	-10000	0	-10000	0	0
SFN	0.039	0.069	0.23	46	-0.38	3	49
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.029	0.12	0.31	7	-10000	0	7
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.01	0.14	0.5	2	-0.8	11	13
JUN	0.029	0.1	0.36	2	-0.37	6	8
IL4	0.005	0.11	-10000	0	-0.49	1	1
CDK5R1	0.027	0.032	0.24	10	-10000	0	10
PRKACA	0.022	0.004	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.13	0.14	-10000	0	-0.38	91	91
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.019	0.11	0.32	8	-10000	0	8
cortisol/GR alpha (monomer)	0.004	0.29	0.59	47	-0.45	41	88
NCOA2	0.021	0.025	-10000	0	-0.53	1	1
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.007	0.19	-10000	0	-0.53	58	58
AP-1/NFAT1-c-4	0.056	0.19	0.36	2	-0.5	13	15
AFP	0.034	0.092	-10000	0	-10000	0	0
SUV420H1	0.022	0.004	-10000	0	-10000	0	0
IRF1	0.005	0.13	0.4	10	-0.38	1	11
TP53	0.029	0.026	-10000	0	-0.53	1	1
PPP5C	0.022	0.004	-10000	0	-10000	0	0
KRT17	0.049	0.17	-10000	0	-0.56	10	10
KRT14	0.032	0.13	0.44	1	-0.66	4	5
TBP	0.026	0.004	-10000	0	-10000	0	0
CREBBP	-0.01	0.044	0.34	1	-10000	0	1
HDAC1	0.021	0.005	-10000	0	-10000	0	0
HDAC2	0.029	0.023	-10000	0	-10000	0	0
AP-1	0.056	0.19	0.36	2	-0.5	13	15
MAPK14	0.021	0.008	-10000	0	-10000	0	0
MAPK10	0.013	0.066	-10000	0	-0.53	7	7
MAPK11	0.021	0.008	-10000	0	-10000	0	0
KRT5	0.049	0.18	-10000	0	-0.79	6	6
interleukin-1 receptor activity	0.007	0.023	-10000	0	-10000	0	0
NCOA1	0.023	0.003	-10000	0	-10000	0	0
STAT1	0.026	0.005	-10000	0	-10000	0	0
CGA	0.01	0.11	-10000	0	-0.49	1	1
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	-0.028	0.18	0.46	38	-0.33	16	54
MAPK3	0.022	0.008	-10000	0	-10000	0	0
MAPK1	0.021	0.008	-10000	0	-10000	0	0
ICAM1	-0.14	0.37	-10000	0	-1.1	53	53
NFKB1	-0.059	0.13	-10000	0	-0.29	57	57
MAPK8	0.022	0.13	0.28	3	-0.36	19	22
MAPK9	0.02	0.009	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.008	0.11	0.5	2	-0.54	5	7
BAX	0.007	0.043	-10000	0	-10000	0	0
POMC	-0.034	0.21	0.48	3	-1.1	8	11
EP300	-0.011	0.044	0.34	1	-10000	0	1
cortisol/GR alpha (dimer)/p53	0.009	0.25	0.51	42	-0.39	33	75
proteasomal ubiquitin-dependent protein catabolic process	-0.005	0.068	0.23	15	-10000	0	15
SGK1	-0.001	0.073	-10000	0	-10000	0	0
IL13	0.002	0.16	-10000	0	-0.64	10	10
IL6	-0.2	0.46	-10000	0	-1.1	91	91
PRKACG	-0.01	0.019	0.23	1	-10000	0	1
IL5	0.001	0.14	-10000	0	-0.68	4	4
IL2	0.012	0.16	-10000	0	-0.57	8	8
CDK5	0.022	0.005	-10000	0	-10000	0	0
PRKACB	0.022	0.004	-10000	0	-10000	0	0
HSP90AA1	0.022	0.005	-10000	0	-10000	0	0
IL8	-0.073	0.23	-10000	0	-0.64	39	39
CDK5R1/CDK5	0.034	0.022	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	-0.063	0.19	-10000	0	-0.44	51	51
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.018	0.23	0.5	45	-0.36	31	76
SMARCA4	0.023	0.005	-10000	0	-10000	0	0
chromatin remodeling	0.005	0.13	0.36	17	-0.36	2	19
NF kappa B1 p50/RelA/Cbp	-0.084	0.2	0.36	1	-0.48	54	55
JUN (dimer)	0.029	0.1	0.36	2	-0.37	6	8
YWHAH	0.022	0.004	-10000	0	-10000	0	0
VIPR1	-0.27	0.45	-10000	0	-0.89	165	165
NR3C1	-0.004	0.17	0.43	24	-0.26	1	25
NR4A1	-0.049	0.19	-10000	0	-0.53	68	68
TIF2/SUV420H1	0.031	0.021	-10000	0	-0.39	1	1
MAPKKK cascade	-0.005	0.11	0.5	3	-0.52	5	8
cortisol/GR alpha (dimer)/Src-1	0.013	0.25	0.51	46	-0.39	38	84
PBX1	0.021	0.036	-10000	0	-0.53	2	2
POU1F1	0.004	0.026	0.23	3	-10000	0	3
SELE	-0.33	0.55	-10000	0	-1.1	159	159
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.005	0.14	0.36	17	-0.36	2	19
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.018	0.23	0.5	45	-0.36	31	76
mol:cortisol	-0.005	0.16	0.32	49	-0.23	47	96
MMP1	0.063	0.11	-10000	0	-0.6	6	6

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.022	0.005	-10000	0	-10000	0	0
CCL5	0.012	0.074	-10000	0	-0.53	9	9
SDCBP	0.022	0.005	-10000	0	-10000	0	0
FGFR/FGF2/Syndecan-1	0.021	0.064	0.28	7	-0.38	3	10
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
Syndecan-1/Laminin-5	0.028	0.071	0.26	8	-0.37	3	11
Syndecan-1/Syntenin	0.03	0.068	0.26	8	-0.36	3	11
MAPK3	0.022	0.063	0.24	8	-0.36	2	10
HGF/MET	-0.053	0.17	0.27	1	-0.39	99	100
TGFB1/TGF beta receptor Type II	0.022	0.005	-10000	0	-10000	0	0
BSG	0.022	0.004	-10000	0	-10000	0	0
keratinocyte migration	0.028	0.07	0.25	8	-0.36	3	11
Syndecan-1/RANTES	0.024	0.086	0.26	7	-0.43	7	14
Syndecan-1/CD147	0.04	0.07	0.28	3	-0.35	3	6
Syndecan-1/Syntenin/PIP2	0.028	0.065	0.27	3	-0.35	3	6
LAMA5	0.021	0.025	-10000	0	-0.53	1	1
positive regulation of cell-cell adhesion	0.027	0.064	0.26	3	-0.34	3	6
MMP7	0.021	0.087	0.23	22	-0.53	9	31
HGF	-0.09	0.22	-10000	0	-0.53	100	100
Syndecan-1/CASK	0.012	0.062	0.22	5	-0.34	4	9
Syndecan-1/HGF/MET	-0.019	0.14	0.29	3	-0.41	20	23
regulation of cell adhesion	0.011	0.058	0.31	1	-0.4	1	2
HPSE	0.022	0.005	-10000	0	-10000	0	0
positive regulation of cell migration	0.021	0.064	0.28	7	-0.38	3	10
SDC1	0.022	0.059	0.27	6	-0.4	2	8
Syndecan-1/Collagen	0.021	0.064	0.28	7	-0.38	3	10
PPIB	0.023	0.002	-10000	0	-10000	0	0
MET	0.02	0.039	0.38	1	-0.53	2	3
PRKACA	0.022	0.004	-10000	0	-10000	0	0
MMP9	0.034	0.049	0.24	27	-10000	0	27
MAPK1	0.019	0.06	0.22	5	-0.34	3	8
homophilic cell adhesion	0.021	0.066	0.28	7	-0.38	3	10
MMP1	0.15	0.11	0.23	303	-0.3	4	307

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.02	0.025	-10000	0	-0.53	1	1
alphaV beta3 Integrin	0.024	0.06	-10000	0	-0.39	10	10
PTK2	0.009	0.14	-10000	0	-0.45	31	31
positive regulation of JNK cascade	0	0.1	-10000	0	-0.32	34	34
CDC42/GDP	0.016	0.14	0.36	1	-0.42	38	39
Rac1/GDP	0.015	0.14	-10000	0	-0.42	37	37
RAP1B	0.022	0.005	-10000	0	-10000	0	0
RAP1A	0.022	0.005	-10000	0	-10000	0	0
CTNNB1	0.021	0.006	-10000	0	-10000	0	0
CDC42/GTP	0.008	0.13	-10000	0	-0.4	33	33
nectin-3/I-afadin	0.001	0.1	-10000	0	-0.39	33	33
RAPGEF1	-0.002	0.14	-10000	0	-0.47	33	33
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.007	0.16	-10000	0	-0.53	33	33
PDGFB-D/PDGFRB	0.02	0.025	-10000	0	-0.53	1	1
TLN1	-0.031	0.099	-10000	0	-0.42	23	23
Rap1/GTP	-0.003	0.1	-10000	0	-0.34	31	31
IQGAP1	0.022	0.004	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.04	0.013	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.001	0.1	-10000	0	-0.39	33	33
PVR	0.022	0.005	-10000	0	-10000	0	0
Necl-5(dimer)	0.022	0.005	-10000	0	-10000	0	0
mol:GDP	0.001	0.17	0.39	1	-0.52	39	40
MLLT4	0.022	0.004	-10000	0	-10000	0	0
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
PI3K	0.019	0.068	-10000	0	-0.29	14	14
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.098	0.075	0.27	1	-0.21	1	2
positive regulation of lamellipodium assembly	0.004	0.11	-10000	0	-0.33	35	35
PVRL1	0.12	0.11	0.23	235	-0.3	1	236
PVRL3	-0.017	0.14	-10000	0	-0.53	33	33
PVRL2	0.022	0.004	-10000	0	-10000	0	0
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
CDH1	0.022	0.005	-10000	0	-10000	0	0
CLDN1	0.063	0.12	0.31	85	-0.53	2	87
JAM-A/CLDN1	0.042	0.099	0.25	30	-0.31	17	47
SRC	-0.012	0.17	-10000	0	-0.58	33	33
ITGB3	0.01	0.082	-10000	0	-0.53	11	11
nectin-1(dimer)/I-afadin/I-afadin	0.098	0.075	0.27	1	-0.21	1	2
FARP2	0.001	0.18	-10000	0	-0.54	34	34
RAC1	0.022	0.004	-10000	0	-10000	0	0
CTNNA1	0.021	0.006	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.014	0.095	-10000	0	-0.33	33	33
nectin-1/I-afadin	0.098	0.075	0.27	1	-0.21	1	2
nectin-2/I-afadin	0.032	0.008	-10000	0	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0.029	0.007	-10000	0	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.061	0.13	-10000	0	-0.35	33	33
CDC42/GTP/IQGAP1/filamentous actin	0.029	0.007	-10000	0	-10000	0	0
F11R	0.022	0.005	-10000	0	-10000	0	0
positive regulation of filopodium formation	0	0.1	-10000	0	-0.32	34	34
alphaV/beta3 Integrin/Talin	0.005	0.13	0.27	4	-0.43	25	29
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.032	0.008	-10000	0	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.032	0.008	-10000	0	-10000	0	0
PIP5K1C	-0.029	0.11	-10000	0	-0.33	47	47
VAV2	0.002	0.17	-10000	0	-0.52	39	39
RAP1/GDP	0.015	0.13	0.36	1	-0.39	36	37
ITGAV	0.022	0.004	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.014	0.095	-10000	0	-0.33	33	33
nectin-3(dimer)/I-afadin/I-afadin	0.001	0.1	-10000	0	-0.39	33	33
Rac1/GTP	0.01	0.14	-10000	0	-0.41	34	34
PTPRM	-0.028	0.12	-10000	0	-0.34	51	51
E-cadherin/beta catenin/alpha catenin	0.1	0.061	-10000	0	-10000	0	0
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.022	0.004	-10000	0	-10000	0	0

×

Wnt signaling

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
Noncanonical Wnts/FZD	0.008	0.077	0.23	2	-0.3	20	22
FZD6	0.022	0.005	-10000	0	-10000	0	0
WNT6	0.054	0.08	0.23	81	-0.3	1	82
WNT4	0.019	0.053	0.23	4	-0.53	4	8
FZD3	0.021	0.007	-10000	0	-10000	0	0
WNT5A	0.023	0.041	0.23	9	-0.42	2	11
WNT11	0.007	0.11	0.24	10	-0.53	18	28

×

FOXM1 transcription factor network

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
NFATC3	0.24	0.24	0.65	1	-1.1	4	5
PLK1	0.1	0.093	-10000	0	-0.49	3	3
BIRC5	0.13	0.066	-10000	0	-0.52	1	1
HSPA1B	0.24	0.24	0.57	2	-1.1	4	6
MAP2K1	0.061	0.04	-10000	0	-10000	0	0
BRCA2	0.24	0.24	-10000	0	-1.2	3	3
FOXM1	0.25	0.28	0.62	2	-1.5	4	6
XRCC1	0.24	0.24	0.65	7	-1.1	4	11
FOXM1B/p19	0.13	0.27	0.58	6	-1.2	5	11
Cyclin D1/CDK4	0.19	0.24	0.6	6	-1.1	4	10
CDC2	0.24	0.25	0.58	3	-1.2	4	7
TGFA	0.22	0.22	0.55	9	-0.96	4	13
SKP2	0.27	0.26	0.68	31	-1.1	3	34
CCNE1	0.084	0.11	0.28	110	-10000	0	110
CKS1B	0.24	0.24	0.54	8	-1.1	4	12
RB1	0.14	0.2	0.42	39	-0.79	7	46
FOXM1C/SP1	0.24	0.25	-10000	0	-1.3	4	4
AURKB	0.086	0.18	-10000	0	-0.92	7	7
CENPF	0.25	0.24	0.68	6	-1.1	4	10
CDK4	0.038	0.025	0.38	1	-10000	0	1
MYC	0.2	0.22	0.5	7	-0.94	4	11
CHEK2	0.059	0.04	-10000	0	-10000	0	0
ONECUT1	0.24	0.24	0.57	11	-1.1	4	15
CDKN2A	0.074	0.14	0.22	207	-0.32	20	227
LAMA4	0.23	0.27	0.59	1	-1.2	7	8
FOXM1B/HNF6	0.24	0.26	0.62	4	-1.4	4	8
FOS	0.13	0.46	0.71	4	-0.98	63	67
SP1	0.023	0.002	-10000	0	-10000	0	0
CDC25B	0.24	0.24	0.66	9	-1.1	4	13
response to radiation	0.033	0.027	-10000	0	-10000	0	0
CENPB	0.24	0.24	0.67	8	-1.1	4	12
CENPA	0.26	0.24	0.66	6	-1.1	4	10
NEK2	0.26	0.24	0.69	6	-1.2	3	9
HIST1H2BA	0.23	0.24	-10000	0	-1.2	3	3
CCNA2	0.083	0.099	0.25	127	-0.29	2	129
EP300	0.022	0.004	-10000	0	-10000	0	0
CCNB1/CDK1	0.23	0.26	-10000	0	-1.3	4	4
CCNB2	0.25	0.24	0.6	1	-1.1	4	5
CCNB1	0.24	0.25	0.6	1	-1.2	4	5
ETV5	0.31	0.29	0.66	69	-1.1	7	76
ESR1	0.2	0.34	0.65	2	-1.1	22	24
CCND1	0.18	0.24	0.6	3	-1.1	4	7
GSK3A	0.051	0.035	-10000	0	-10000	0	0
Cyclin A-E1/CDK1-2	0.14	0.11	0.31	100	-10000	0	100
CDK2	0.03	0.012	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.041	0.033	-10000	0	-10000	0	0
FOXM1B/Cbp/p300	0.22	0.24	-10000	0	-1.2	4	4
GAS1	0.22	0.28	0.69	1	-1.2	10	11
MMP2	0.23	0.26	0.71	1	-1.2	7	8
RB1/FOXM1C	0.2	0.26	0.58	16	-1.2	4	20
CREBBP	0.022	0.005	-10000	0	-10000	0	0

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.046	0.1	-10000	0	-0.38	14	14
epithelial cell differentiation	-0.022	0.086	-10000	0	-0.41	4	4
ITCH	0.037	0.021	-10000	0	-10000	0	0
WWP1	-0.037	0.076	-10000	0	-10000	0	0
FYN	0.021	0.025	-10000	0	-0.53	1	1
EGFR	0.023	0.081	0.36	12	-0.53	6	18
PRL	0.001	0.035	0.23	8	-10000	0	8
neuron projection morphogenesis	-0.03	0.077	-10000	0	-0.34	5	5
PTPRZ1	0.15	0.13	0.23	320	-0.48	9	329
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.011	0.09	-10000	0	-0.37	5	5
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.036	0.082	-10000	0	-0.34	13	13
ADAM17	0.037	0.022	-10000	0	-10000	0	0
ErbB4/ErbB4	-0.053	0.091	-10000	0	-0.29	5	5
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.12	0.17	-10000	0	-0.38	123	123
NCOR1	0.022	0.005	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.031	0.085	-10000	0	-0.38	7	7
GRIN2B	-0.034	0.081	-10000	0	-0.37	6	6
ErbB4/ErbB2/betacellulin	-0.04	0.11	-10000	0	-0.38	18	18
STAT1	0.022	0.004	-10000	0	-10000	0	0
HBEGF	0.004	0.095	-10000	0	-0.53	15	15
PRLR	0.019	0.098	0.29	21	-0.53	10	31
E4ICDs/ETO2	-0.041	0.097	-10000	0	-0.39	5	5
axon guidance	-0.034	0.071	-10000	0	-0.43	2	2
NEDD4	0.037	0.022	-10000	0	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	0.026	0.075	0.28	9	-0.39	10	19
CBFA2T3	0.016	0.056	-10000	0	-0.53	5	5
ErbB4/ErbB2/HBEGF	-0.028	0.086	-10000	0	-0.36	8	8
MAPK3	-0.022	0.084	-10000	0	-0.35	5	5
STAT1 (dimer)	-0.037	0.09	-10000	0	-10000	0	0
MAPK1	-0.021	0.081	-10000	0	-0.35	5	5
JAK2	0.02	0.007	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.034	0.082	-10000	0	-0.39	6	6
NRG1	-0.006	0.068	-10000	0	-0.39	14	14
NRG3	-0.13	0.24	-10000	0	-0.53	126	126
NRG2	-0.036	0.16	-10000	0	-0.53	48	48
NRG4	0.046	0.069	0.23	59	-0.3	1	60
heart development	-0.034	0.071	-10000	0	-0.43	2	2
neural crest cell migration	-0.033	0.081	-10000	0	-0.38	6	6
ERBB2	0.008	0.028	0.31	2	-10000	0	2
WWOX/E4ICDs	-0.035	0.088	-10000	0	-10000	0	0
SHC1	0.022	0.005	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.018	0.12	0.29	1	-0.42	3	4
apoptosis	0.16	0.24	0.5	135	-10000	0	135
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.068	0.13	-10000	0	-0.38	45	45
ErbB4/ErbB2/epiregulin	-0.068	0.14	-10000	0	-0.38	48	48
ErbB4/ErbB4/betacellulin/betacellulin	-0.06	0.13	-10000	0	-0.38	35	35
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.021	0.11	0.37	1	-0.41	9	10
MDM2	-0.042	0.086	0.25	6	-10000	0	6
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.021	0.072	-10000	0	-0.36	6	6
STAT5A	-0.034	0.068	-10000	0	-0.41	2	2
ErbB4/EGFR/neuregulin 1 beta	-0.027	0.1	0.27	2	-0.43	11	13
DLG4	0.021	0.005	-10000	0	-10000	0	0
GRB2/SHC	0.031	0.009	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.036	0.082	-10000	0	-10000	0	0
STAT5A (dimer)	-0.019	0.095	-10000	0	-0.48	3	3
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.024	0.076	-10000	0	-0.41	2	2
LRIG1	0.02	0.026	-10000	0	-0.53	1	1
EREG	-0.072	0.22	0.24	14	-0.53	89	103
BTC	-0.019	0.14	-10000	0	-0.53	36	36
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.034	0.07	-10000	0	-0.43	2	2
ERBB4	-0.051	0.091	-10000	0	-0.29	5	5
STAT5B	0.022	0.003	-10000	0	-10000	0	0
YAP1	-0.009	0.076	-10000	0	-0.52	9	9
GRB2	0.022	0.004	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.013	0.09	0.31	3	-10000	0	3
glial cell differentiation	0.036	0.082	-10000	0	-10000	0	0
WWOX	0.021	0.006	-10000	0	-10000	0	0
cell proliferation	-0.056	0.12	0.32	1	-0.47	13	14

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	0.031	0.069	-10000	0	-0.33	12	12
fibroblast growth factor receptor signaling pathway	0.03	0.068	-10000	0	-0.33	12	12
LAMA1	0.082	0.1	0.24	142	-0.42	2	144
PRNP	0.022	0.005	-10000	0	-10000	0	0
GPC1/SLIT2	-0.051	0.17	-10000	0	-0.4	96	96
SMAD2	-0.029	0.067	0.18	5	-0.3	24	29
GPC1/PrPc/Cu2+	0.035	0.03	-10000	0	-10000	0	0
GPC1/Laminin alpha1	0.08	0.084	0.31	23	-0.3	2	25
TDGF1	0.014	0.024	0.23	3	-10000	0	3
CRIPTO/GPC1	0.038	0.035	-10000	0	-10000	0	0
APP/GPC1	0.039	0.034	-10000	0	-10000	0	0
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.014	0.012	-10000	0	-10000	0	0
FLT1	0.021	0.006	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	0.026	0.092	-10000	0	-0.33	25	25
SERPINC1	0.014	0.03	0.23	6	-10000	0	6
FYN	-0.015	0.018	-10000	0	-0.3	1	1
FGR	-0.035	0.08	-10000	0	-0.34	32	32
positive regulation of MAPKKK cascade	-0.018	0.1	0.31	3	-0.36	21	24
SLIT2	-0.087	0.22	-10000	0	-0.53	97	97
GPC1/NRG	0.025	0.079	-10000	0	-0.39	14	14
NRG1	0.004	0.092	-10000	0	-0.53	14	14
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.049	0.033	-10000	0	-10000	0	0
LYN	-0.015	0.023	-10000	0	-0.33	2	2
mol:Spermine	-0.008	0.013	-10000	0	-10000	0	0
cell growth	0.03	0.068	-10000	0	-0.33	12	12
BMP signaling pathway	-0.033	0.047	-10000	0	-0.23	27	27
SRC	-0.014	0.012	-10000	0	-10000	0	0
TGFBR1	0.022	0.004	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.14	0.25	0.23	2	-0.53	140	142
GPC1	0.033	0.047	0.23	27	-10000	0	27
TGFBR1 (dimer)	0.022	0.004	-10000	0	-10000	0	0
VEGFA	0.022	0.004	-10000	0	-10000	0	0
BLK	-0.018	0.053	-10000	0	-0.34	11	11
HCK	-0.016	0.028	-10000	0	-0.34	3	3
FGF2	0.008	0.085	-10000	0	-0.53	12	12
FGFR1	0.017	0.026	-10000	0	-0.53	1	1
VEGFR1 homodimer	0.021	0.006	-10000	0	-10000	0	0
TGFBR2	-0.007	0.12	-10000	0	-0.53	25	25
cell death	0.039	0.033	-10000	0	-10000	0	0
ATIII/GPC1	0.039	0.036	-10000	0	-10000	0	0
PLA2G2A/GPC1	-0.086	0.2	-10000	0	-0.39	140	140
LCK	-0.015	0.019	-10000	0	-0.34	1	1
neuron differentiation	0.025	0.079	-10000	0	-0.39	14	14
PrPc/Cu2+	0.016	0.004	-10000	0	-10000	0	0
APP	0.022	0.005	-10000	0	-10000	0	0
TGFBR2 (dimer)	-0.007	0.12	-10000	0	-0.53	25	25

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.032	0.06	0.3	6	-0.21	20	26
TP53	-0.003	0.048	-10000	0	-0.19	24	24
Senescence	-0.004	0.05	-10000	0	-0.2	25	25
Apoptosis	-0.004	0.05	-10000	0	-0.2	25	25
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	-0.001	0.073	0.23	35	-0.21	6	41
MDM4	0.022	0.004	-10000	0	-10000	0	0

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	-0.024	0.15	0.28	1	-0.48	38	39
ACTA1	-0.033	0.14	0.27	3	-0.52	30	33
NUMA1	-0.028	0.16	0.28	1	-0.49	41	42
SPTAN1	-0.036	0.14	0.32	3	-0.52	30	33
LIMK1	-0.034	0.14	0.31	2	-0.52	29	31
BIRC3	0.015	0.061	-10000	0	-0.53	6	6
BIRC2	0.022	0.004	-10000	0	-10000	0	0
BAX	0.022	0.004	-10000	0	-10000	0	0
CASP10	-0.03	0.091	-10000	0	-0.43	23	23
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.022	0.003	-10000	0	-10000	0	0
PTK2	-0.024	0.15	0.26	1	-0.49	36	37
DIABLO	0.023	0.002	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.035	0.14	0.32	3	-0.51	30	33
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.023	0.002	-10000	0	-10000	0	0
GSN	-0.036	0.14	0.31	2	-0.53	29	31
MADD	0.022	0.004	-10000	0	-10000	0	0
TFAP2A	0.081	0.18	-10000	0	-0.7	21	21
BID	-0.007	0.05	-10000	0	-0.25	19	19
MAP3K1	-0.035	0.16	-10000	0	-0.57	34	34
TRADD	0.022	0.005	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.032	0.007	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.026	0.15	0.32	3	-0.55	26	29
CASP9	0.022	0.005	-10000	0	-10000	0	0
DNA repair	0.002	0.046	0.2	9	-0.16	2	11
neuron apoptosis	-0.011	0.15	-10000	0	-0.73	18	18
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.034	0.16	0.29	1	-0.51	39	40
APAF1	0.023	0.002	-10000	0	-10000	0	0
CASP6	-0.032	0.22	-10000	0	-0.98	22	22
TRAF2	0.022	0.004	-10000	0	-10000	0	0
ICAD/CAD	-0.035	0.14	0.33	3	-0.52	28	31
CASP7	-0.005	0.066	0.31	5	-0.27	4	9
KRT18	0.009	0.046	-10000	0	-0.62	1	1
apoptosis	-0.04	0.16	0.41	1	-0.56	33	34
DFFA	-0.035	0.14	0.29	1	-0.52	30	31
DFFB	-0.035	0.14	0.29	1	-0.53	29	30
PARP1	-0.002	0.047	0.16	2	-0.2	9	11
actin filament polymerization	0.029	0.14	0.48	28	-0.34	7	35
TNF	0.012	0.079	0.23	1	-0.53	10	11
CYCS	-0.002	0.06	0.18	8	-0.23	19	27
SATB1	-0.033	0.2	-10000	0	-0.91	22	22
SLK	-0.036	0.14	0.32	1	-0.52	30	31
p15 BID/BAX	0.006	0.063	0.2	3	-0.3	11	14
CASP2	0.007	0.051	0.2	2	-0.37	2	4
JNK cascade	0.035	0.16	0.57	34	-10000	0	34
CASP3	-0.035	0.15	0.32	1	-0.55	30	31
LMNB2	-0.004	0.12	0.28	3	-0.44	24	27
RIPK1	0.022	0.004	-10000	0	-10000	0	0
CASP4	0.021	0.025	-10000	0	-0.53	1	1
Mammalian IAPs/DIABLO	0.051	0.042	-10000	0	-0.31	6	6
negative regulation of DNA binding	0.082	0.18	-10000	0	-0.68	21	21
stress fiber formation	-0.035	0.14	0.31	1	-0.5	30	31
GZMB	-0.033	0.11	-10000	0	-0.49	24	24
CASP1	0.008	0.039	-10000	0	-0.56	2	2
LMNB1	-0.024	0.19	0.28	3	-0.58	37	40
APP	-0.011	0.15	-10000	0	-0.75	18	18
TNFRSF1A	0.021	0.006	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	-0.005	0.002	-10000	0	-10000	0	0
VIM	-0.038	0.16	0.4	1	-0.55	36	37
LMNA	0.004	0.099	0.28	3	-0.4	19	22
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.01	0.056	-10000	0	-0.35	3	3
LRDD	0	0	-10000	0	-10000	0	0
SREBF1	-0.035	0.14	0.32	2	-0.53	29	31
APAF-1/Caspase 9	-0.007	0.13	-10000	0	-0.64	19	19
nuclear fragmentation during apoptosis	-0.027	0.15	0.27	1	-0.48	41	42
CFL2	-0.03	0.14	0.34	7	-0.5	28	35
GAS2	-0.063	0.16	-10000	0	-0.42	66	66
positive regulation of apoptosis	-0.008	0.15	0.29	3	-0.5	29	32
PRF1	-0.002	0.11	-10000	0	-0.53	21	21

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.005	0.092	-10000	0	-0.39	24	24
PDGFRB	0.019	0.026	-10000	0	-0.54	1	1
SPHK1	0	0.054	-10000	0	-0.73	2	2
mol:S1P	-0.004	0.053	-10000	0	-0.64	2	2
S1P1/S1P/Gi	-0.049	0.16	-10000	0	-0.42	64	64
GNAO1	0.017	0.032	0.22	2	-0.53	1	3
PDGFB-D/PDGFRB/PLCgamma1	-0.032	0.15	0.25	3	-0.38	61	64
PLCG1	-0.051	0.15	-10000	0	-0.4	64	64
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.019	0.026	-10000	0	-0.54	1	1
GNAI2	0.016	0.016	-10000	0	-10000	0	0
GNAI3	0.018	0.015	-10000	0	-10000	0	0
GNAI1	0.016	0.029	-10000	0	-0.54	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	-0.024	0.07	-10000	0	-0.33	24	24
S1P1/S1P	-0.018	0.078	-10000	0	-0.35	10	10
negative regulation of cAMP metabolic process	-0.047	0.16	-10000	0	-0.41	64	64
MAPK3	-0.072	0.21	-10000	0	-0.56	69	69
calcium-dependent phospholipase C activity	-0.001	0.003	-10000	0	-10000	0	0
Rac1/GDP	0.016	0.003	-10000	0	-10000	0	0
RhoA/GDP	0.015	0.005	-10000	0	-10000	0	0
KDR	-0.01	0.12	-10000	0	-0.53	25	25
PLCB2	-0.009	0.088	0.25	4	-0.33	8	12
RAC1	0.022	0.004	-10000	0	-10000	0	0
RhoA/GTP	-0.012	0.069	-10000	0	-0.32	8	8
receptor internalization	-0.018	0.073	-10000	0	-0.33	10	10
PTGS2	-0.1	0.33	0.34	1	-0.95	58	59
Rac1/GTP	-0.012	0.069	-10000	0	-0.31	9	9
RHOA	0.021	0.007	-10000	0	-10000	0	0
VEGFA	0.019	0.013	-10000	0	-10000	0	0
negative regulation of T cell proliferation	-0.047	0.16	-10000	0	-0.41	64	64
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	0.012	0.057	-10000	0	-0.54	5	5
MAPK1	-0.064	0.19	-10000	0	-0.54	65	65
S1P1/S1P/PDGFB-D/PDGFRB	-0.008	0.092	0.28	1	-0.37	10	11
ABCC1	0.019	0.017	0.24	1	-10000	0	1

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	-0.008	0.023	0.24	1	-0.25	1	2
RFC1	-0.006	0.031	0.22	5	-0.25	1	6
PRKDC	-0.003	0.044	0.22	13	-0.25	1	14
RIPK1	0.023	0.005	-10000	0	-10000	0	0
CASP7	-0.016	0.12	-10000	0	-0.6	18	18
FASLG/FAS/FADD/FAF1	-0.006	0.061	0.21	4	-0.28	18	22
MAP2K4	-0.02	0.15	0.33	3	-0.42	23	26
mol:ceramide	-0.018	0.095	-10000	0	-0.36	20	20
GSN	-0.008	0.023	0.24	1	-0.25	1	2
FASLG/FAS/FADD/FAF1/Caspase 8	-0.007	0.086	-10000	0	-0.34	21	21
FAS	0.013	0.032	-10000	0	-0.55	1	1
BID	-0.014	0.055	0.51	4	-10000	0	4
MAP3K1	0.009	0.13	0.35	5	-0.46	20	25
MAP3K7	0.017	0.015	-10000	0	-10000	0	0
RB1	-0.008	0.029	0.23	2	-0.3	2	4
CFLAR	0.023	0.005	-10000	0	-10000	0	0
HGF/MET	-0.035	0.15	0.25	1	-0.34	99	100
ARHGDIB	0.001	0.053	0.22	23	-0.25	1	24
FADD	0.013	0.018	-10000	0	-10000	0	0
actin filament polymerization	0.019	0.046	0.25	1	-0.24	1	2
NFKB1	-0.033	0.14	-10000	0	-0.67	16	16
MAPK8	-0.049	0.19	0.45	1	-0.43	84	85
DFFA	-0.007	0.027	0.23	2	-0.25	1	3
DNA fragmentation during apoptosis	-0.015	0.047	0.22	4	-0.25	1	5
FAS/FADD/MET	0.025	0.043	0.25	1	-0.34	3	4
CFLAR/RIP1	0.034	0.01	-10000	0	-10000	0	0
FAIM3	0.019	0.051	0.23	1	-0.53	4	5
FAF1	0.014	0.022	-10000	0	-10000	0	0
PARP1	-0.006	0.035	0.22	6	-0.2	4	10
DFFB	-0.006	0.031	0.22	4	-0.25	1	5
CHUK	-0.03	0.13	-10000	0	-0.61	16	16
FASLG	-0.007	0.11	-10000	0	-0.54	19	19
FAS/FADD	0.017	0.033	-10000	0	-0.42	1	1
HGF	-0.09	0.22	-10000	0	-0.53	100	100
LMNA	-0.011	0.043	0.21	1	-10000	0	1
CASP6	-0.006	0.027	0.23	3	-0.25	1	4
CASP10	0.013	0.031	-10000	0	-0.53	1	1
CASP3	-0.003	0.021	0.25	2	-0.28	1	3
PTPN13	0.018	0.043	-10000	0	-0.53	3	3
CASP8	-0.016	0.044	0.44	4	-10000	0	4
IL6	-0.19	0.49	-10000	0	-1.2	89	89
MET	0.02	0.039	0.38	1	-0.53	2	3
ICAD/CAD	-0.008	0.03	0.26	3	-0.24	1	4
FASLG/FAS/FADD/FAF1/Caspase 10	-0.018	0.096	-10000	0	-0.37	20	20
activation of caspase activity by cytochrome c	-0.014	0.054	0.51	4	-10000	0	4
PAK2	0.059	0.1	0.22	150	-10000	0	150
BCL2	0.023	0.016	0.38	1	-10000	0	1

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.021	0.006	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.04	0.091	-10000	0	-0.26	23	23
NT3 (dimer)/TRKC	-0.088	0.19	-10000	0	-0.4	134	134
NT3 (dimer)/TRKB	0.04	0.13	0.31	2	-0.36	34	36
SHC/Grb2/SOS1/GAB1/PI3K	0.009	0.022	-10000	0	-10000	0	0
RAPGEF1	0.022	0.003	-10000	0	-10000	0	0
BDNF	-0.045	0.18	-10000	0	-0.53	60	60
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
DYNLT1	0.022	0.003	-10000	0	-10000	0	0
NTRK1	0.016	0.056	-10000	0	-0.53	5	5
NTRK2	0.02	0.16	0.23	79	-0.53	32	111
NTRK3	-0.14	0.25	0.23	3	-0.53	140	143
NT-4/5 (dimer)/TRKB	0.043	0.13	0.27	5	-0.36	36	41
neuron apoptosis	0.042	0.17	0.41	48	-10000	0	48
SHC 2-3/Grb2	-0.047	0.18	-10000	0	-0.45	48	48
SHC1	0.022	0.005	-10000	0	-10000	0	0
SHC2	0.004	0.12	-10000	0	-0.43	16	16
SHC3	-0.074	0.22	-10000	0	-0.51	87	87
STAT3 (dimer)	0.022	0.042	-10000	0	-0.35	6	6
NT3 (dimer)/TRKA	0.043	0.068	0.25	1	-0.34	10	11
RIN/GDP	-0.026	0.089	0.24	4	-0.28	5	9
GIPC1	0.022	0.004	-10000	0	-10000	0	0
KRAS	0.021	0.006	-10000	0	-10000	0	0
DNAJA3	0.028	0.058	0.23	1	-0.24	5	6
RIN/GTP	0.012	0.003	-10000	0	-10000	0	0
CCND1	0.001	0.089	0.36	1	-0.79	6	7
MAGED1	0.022	0.004	-10000	0	-10000	0	0
PTPN11	0.023	0.002	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.013	0.07	-10000	0	-0.53	8	8
SHC/GRB2/SOS1	0.042	0.014	-10000	0	-10000	0	0
GRB2	0.022	0.004	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	0.018	0.094	0.25	1	-0.33	31	32
TRKA/NEDD4-2	0.027	0.043	-10000	0	-0.39	5	5
ELMO1	0.014	0.065	-10000	0	-0.53	7	7
RhoG/GTP/ELMO1/DOCK1	0.023	0.044	-10000	0	-0.33	7	7
NGF	0.013	0.077	0.28	3	-0.53	9	12
HRAS	0.022	0.004	-10000	0	-10000	0	0
DOCK1	0.022	0.004	-10000	0	-10000	0	0
GAB2	0.006	0.092	-10000	0	-0.53	14	14
RIT2	-0.015	0.011	-10000	0	-10000	0	0
RIT1	0.022	0.005	-10000	0	-10000	0	0
FRS2	0.022	0.005	-10000	0	-10000	0	0
DNM1	0.023	0.014	0.23	2	-10000	0	2
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.021	0.005	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	0.036	0.062	-10000	0	-0.24	9	9
mol:GDP	-0.04	0.12	0.31	5	-0.4	10	15
NGF (dimer)	0.013	0.077	0.28	3	-0.53	9	12
RhoG/GDP	0.01	0.049	-10000	0	-0.39	7	7
RIT1/GDP	-0.023	0.087	0.26	3	-0.28	5	8
TIAM1	0.021	0.025	-10000	0	-0.53	1	1
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.004	0.18	0.25	1	-0.38	78	79
KIDINS220/CRKL/C3G	0.031	0.01	-10000	0	-10000	0	0
SHC/RasGAP	0.03	0.011	-10000	0	-10000	0	0
FRS2 family/SHP2	0.043	0.013	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0.05	0.021	-10000	0	-10000	0	0
RIT1/GTP	0.016	0.004	-10000	0	-10000	0	0
NT3 (dimer)	0.014	0.067	0.23	2	-0.53	7	9
RAP1/GDP	-0.024	0.072	-10000	0	-0.24	6	6
KIDINS220/CRKL	0.021	0.006	-10000	0	-10000	0	0
BDNF (dimer)	-0.044	0.18	-10000	0	-0.53	60	60
ubiquitin-dependent protein catabolic process	0.03	0.066	0.25	1	-0.34	14	15
Schwann cell development	-0.039	0.03	-10000	0	-10000	0	0
EHD4	0.022	0.003	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.052	0.019	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.011	0.054	-10000	0	-0.32	4	4
RAP1B	0.022	0.005	-10000	0	-10000	0	0
RAP1A	0.022	0.005	-10000	0	-10000	0	0
CDC42/GTP	-0.091	0.2	-10000	0	-0.34	169	169
ABL1	0.022	0.003	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.032	0.008	-10000	0	-10000	0	0
Rap1/GTP	-0.016	0.091	-10000	0	-0.38	8	8
STAT3	0.022	0.042	-10000	0	-0.35	6	6
axon guidance	-0.094	0.18	-10000	0	-0.32	169	169
MAPK3	-0.026	0.079	0.18	15	-0.3	30	45
MAPK1	-0.026	0.077	0.18	13	-0.3	29	42
CDC42/GDP	-0.022	0.092	0.26	5	-0.28	6	11
NTF3	0.014	0.067	0.23	2	-0.53	7	9
NTF4	0.013	0.07	-10000	0	-0.53	8	8
NGF (dimer)/TRKA/FAIM	0.026	0.065	0.25	1	-0.34	13	14
PI3K	0.017	0.017	-10000	0	-10000	0	0
FRS3	0.022	0.004	-10000	0	-10000	0	0
FAIM	0.019	0.009	-10000	0	-10000	0	0
GAB1	0.021	0.006	-10000	0	-10000	0	0
RASGRF1	-0.12	0.14	-10000	0	-0.28	143	143
SOS1	0.022	0.004	-10000	0	-10000	0	0
MCF2L	-0.1	0.15	0.25	1	-0.34	133	134
RGS19	0.022	0.004	-10000	0	-10000	0	0
CDC42	0.022	0.004	-10000	0	-10000	0	0
RAS family/GTP	-0.021	0.08	0.37	1	-0.42	4	5
Rac1/GDP	-0.023	0.091	0.24	4	-0.28	6	10
NGF (dimer)/TRKA/GRIT	0.018	0.062	0.24	1	-0.33	14	15
neuron projection morphogenesis	0.034	0.12	-10000	0	-0.81	7	7
NGF (dimer)/TRKA/NEDD4-2	0.031	0.066	0.25	1	-0.34	14	15
MAP2K1	0.001	0.057	0.55	1	-10000	0	1
NGFR	0.041	0.062	0.24	43	-10000	0	43
NGF (dimer)/TRKA/GIPC/GAIP	0.012	0.047	-10000	0	-0.26	12	12
RAS family/GTP/PI3K	0.009	0.01	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	0.06	0.023	-10000	0	-10000	0	0
NRAS	0.022	0.005	-10000	0	-10000	0	0
GRB2/SOS1	0.032	0.008	-10000	0	-10000	0	0
PRKCI	0.013	0.011	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.022	0.004	-10000	0	-10000	0	0
PRKCZ	0.022	0.005	-10000	0	-10000	0	0
MAPKKK cascade	-0.028	0.14	-10000	0	-0.56	24	24
RASA1	0.021	0.006	-10000	0	-10000	0	0
TRKA/c-Abl	0.028	0.043	-10000	0	-0.39	5	5
SQSTM1	0.021	0.006	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	0.008	0.17	0.25	1	-0.35	75	76
NGF (dimer)/TRKA/p62/Atypical PKCs	0.027	0.059	-10000	0	-0.29	10	10
MATK	0.001	0.11	-10000	0	-0.53	19	19
NEDD4L	0.022	0.005	-10000	0	-10000	0	0
RAS family/GDP	-0.037	0.056	-10000	0	-0.24	2	2
NGF (dimer)/TRKA	0.005	0.045	0.19	1	-0.25	7	8
Rac1/GTP	-0.1	0.098	-10000	0	-0.26	67	67
FRS2 family/SHP2/CRK family	0.056	0.026	-10000	0	-10000	0	0

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.022	0.005	-10000	0	-10000	0	0
VLDLR	0.019	0.026	-10000	0	-0.53	1	1
LRPAP1	0.021	0.006	-10000	0	-10000	0	0
NUDC	0.022	0.004	-10000	0	-10000	0	0
RELN/LRP8	-0.018	0.14	-10000	0	-0.33	78	78
CaM/Ca2+	0.016	0.004	-10000	0	-10000	0	0
KATNA1	0.022	0.003	-10000	0	-10000	0	0
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	-0.051	0.12	-10000	0	-0.3	78	78
IQGAP1/CaM	0.032	0.009	-10000	0	-10000	0	0
DAB1	0.026	0.056	0.24	29	-10000	0	29
IQGAP1	0.022	0.004	-10000	0	-10000	0	0
PLA2G7	0.018	0.05	-10000	0	-0.53	4	4
CALM1	0.022	0.005	-10000	0	-10000	0	0
DYNLT1	0.022	0.003	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	0.031	0.013	-10000	0	-10000	0	0
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0.023	0.002	-10000	0	-10000	0	0
CDK5R1	0.027	0.032	0.24	10	-10000	0	10
LIS1/Poliovirus Protein 3A	-0.007	0.003	-10000	0	-10000	0	0
CDK5R2	0.071	0.096	0.23	128	-0.3	2	130
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.015	0.14	0.35	2	-0.33	76	78
YWHAE	0.022	0.005	-10000	0	-10000	0	0
NDEL1/14-3-3 E	-0.015	0.11	0.31	2	-0.32	5	7
MAP1B	0.005	0.01	0.21	1	-10000	0	1
RAC1	0.009	0.004	-10000	0	-10000	0	0
p35/CDK5	-0.046	0.11	0.28	1	-0.28	73	74
RELN	-0.065	0.2	0.23	3	-0.53	78	81
PAFAH/LIS1	0.019	0.028	-10000	0	-0.33	3	3
LIS1/CLIP170	0.021	0.007	-10000	0	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.009	0.092	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.035	0.12	-10000	0	-0.33	40	40
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	-0.033	0.11	0.34	1	-0.32	10	11
LIS1/IQGAP1	0.021	0.008	-10000	0	-10000	0	0
RHOA	0.009	0.004	-10000	0	-10000	0	0
PAFAH1B1	-0.009	0.003	-10000	0	-10000	0	0
PAFAH1B3	0.025	0.029	0.34	4	-10000	0	4
PAFAH1B2	0.022	0.004	-10000	0	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0.015	0.027	-10000	0	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.007	0.11	0.3	2	-0.34	2	4
LRP8	0.023	0.016	0.23	3	-10000	0	3
NDEL1/Katanin 60	-0.018	0.11	0.31	2	-0.32	6	8
P39/CDK5	-0.017	0.14	0.3	7	-0.29	67	74
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.021	0.008	-10000	0	-10000	0	0
CDK5	-0.051	0.11	-10000	0	-0.29	77	77
PPP2R5D	0.022	0.004	-10000	0	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.018	0.006	-10000	0	-10000	0	0
CSNK2A1	0.022	0.005	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.004	0.12	0.29	2	-0.29	68	70
RELN/VLDLR	-0.007	0.13	-10000	0	-0.3	76	76
CDC42	0.009	0.004	-10000	0	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.024	0.093	-10000	0	-0.33	29	29
MAP4K1	0.016	0.05	-10000	0	-0.53	4	4
MAP3K8	0.021	0.025	-10000	0	-0.53	1	1
PRKCB	-0.006	0.12	-10000	0	-0.53	25	25
DBNL	0.022	0.005	-10000	0	-10000	0	0
CRKL	0.021	0.006	-10000	0	-10000	0	0
MAP3K1	-0.002	0.079	-10000	0	-0.31	21	21
JUN	-0.037	0.2	-10000	0	-0.64	43	43
MAP3K7	-0.009	0.088	-10000	0	-0.3	29	29
GRAP2	-0.008	0.13	-10000	0	-0.53	27	27
CRK	0.021	0.005	-10000	0	-10000	0	0
MAP2K4	0.002	0.096	0.28	5	-0.51	8	13
LAT	0.022	0.003	-10000	0	-10000	0	0
LCP2	0.015	0.056	-10000	0	-0.53	5	5
MAPK8	-0.036	0.21	-10000	0	-0.68	43	43
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0	0.092	-10000	0	-0.3	33	33
LAT/GRAP2/SLP76/HPK1/HIP-55	0.032	0.091	-10000	0	-0.31	28	28

×

Visual signal transduction: Rods

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
mol:K +	0.023	0.002	-10000	0	-10000	0	0
GNAT1/GTP	0.015	0.02	0.16	7	-0.2	1	8
Metarhodopsin II/Arrestin	0.023	0.012	-10000	0	-10000	0	0
PDE6G/GNAT1/GTP	0.021	0.053	-10000	0	-0.32	10	10
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	0.008	0.035	0.23	7	-0.3	1	8
GRK1	-0.004	0.03	0.38	2	-10000	0	2
CNG Channel	0.028	0.077	-10000	0	-0.29	20	20
mol:Na +	0.058	0.058	-10000	0	-10000	0	0
mol:ADP	-0.004	0.03	0.38	2	-10000	0	2
RGS9-1/Gbeta5/R9AP	-0.003	0.12	-10000	0	-0.34	57	57
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	0.074	0.069	0.25	22	-10000	0	22
CNGB1	0.04	0.061	0.23	44	-10000	0	44
RDH5	0.02	0.035	-10000	0	-0.53	2	2
SAG	-0.013	0.013	-10000	0	-10000	0	0
mol:Ca2+	-0.004	0.09	0.35	14	-10000	0	14
Na + (4 Units)	0.044	0.043	-10000	0	-10000	0	0
RGS9	-0.036	0.17	-10000	0	-0.53	52	52
GNB1/GNGT1	0.077	0.078	0.27	19	-0.39	1	20
GNAT1/GDP	0.005	0.11	-10000	0	-0.3	57	57
GUCY2D	0.02	0.009	-10000	0	-10000	0	0
GNGT1	0.092	0.11	0.25	155	-10000	0	155
GUCY2F	-0.006	0.019	-10000	0	-10000	0	0
GNB5	0.023	0.003	-10000	0	-10000	0	0
mol:GMP (4 units)	0.001	0.068	-10000	0	-0.3	22	22
mol:11-cis-retinal	0.02	0.035	-10000	0	-0.53	2	2
mol:cGMP	0.062	0.062	0.27	3	-10000	0	3
GNB1	0.021	0.025	-10000	0	-0.53	1	1
Rhodopsin	0.027	0.03	-10000	0	-0.4	2	2
SLC24A1	0.023	0.002	-10000	0	-10000	0	0
CNGA1	0.024	0.024	0.23	6	-10000	0	6
Metarhodopsin II	0.022	0.017	0.22	2	-10000	0	2
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.073	0.063	-10000	0	-10000	0	0
RGS9BP	0.011	0.074	-10000	0	-0.53	9	9
Metarhodopsin II/Transducin	0.023	0.045	0.17	15	-0.2	3	18
GCAP Family/Ca ++	0.063	0.059	-10000	0	-10000	0	0
PDE6A/B	0.017	0.075	-10000	0	-0.39	15	15
mol:Pi	-0.003	0.12	-10000	0	-0.34	57	57
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	0.071	0.069	0.24	19	-0.31	1	20
PDE6B	0.014	0.062	0.23	1	-0.53	6	7
PDE6A	0.011	0.075	0.23	2	-0.53	9	11
PDE6G	0.012	0.074	-10000	0	-0.53	9	9
RHO	0	0.024	0.23	2	-10000	0	2
PDE6	0.002	0.14	-10000	0	-0.32	65	65
GUCA1A	0.076	0.097	0.23	134	-0.3	2	136
GC2/GCAP Family	0.072	0.062	-10000	0	-10000	0	0
GUCA1C	-0.016	0.006	-10000	0	-10000	0	0
GUCA1B	0.022	0.005	-10000	0	-10000	0	0

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.051	0.19	-10000	0	-0.53	65	65
GNB1/GNG2	0.018	0.094	0.26	1	-0.35	10	11
mol:DAG	-0.004	0.075	0.22	1	-0.34	7	8
PLCG1	-0.004	0.077	0.22	1	-0.35	7	8
YES1	-0.004	0.073	0.22	4	-0.29	19	23
FZD3	0.021	0.007	-10000	0	-10000	0	0
FZD6	0.022	0.005	-10000	0	-10000	0	0
G protein	0.013	0.09	0.24	1	-0.38	7	8
MAP3K7	-0.026	0.092	0.19	1	-0.38	14	15
mol:Ca2+	-0.004	0.073	0.22	1	-0.33	7	8
mol:IP3	-0.004	0.075	0.22	1	-0.34	7	8
NLK	0.005	0.072	-10000	0	-0.78	4	4
GNB1	0.021	0.025	-10000	0	-0.53	1	1
CAMK2A	-0.019	0.099	0.2	1	-0.4	15	16
MAP3K7IP1	0	0	-10000	0	-10000	0	0
Noncanonical Wnts/FZD	0.008	0.077	0.23	2	-0.3	20	22
CSNK1A1	0.021	0.006	-10000	0	-10000	0	0
GNAS	-0.004	0.074	0.24	4	-0.29	19	23
GO:0007205	-0.011	0.073	0.21	1	-0.34	7	8
WNT6	0.054	0.08	0.23	81	-0.3	1	82
WNT4	0.019	0.053	0.23	4	-0.53	4	8
NFAT1/CK1 alpha	-0.012	0.14	0.27	2	-0.41	22	24
GNG2	0.016	0.055	-10000	0	-0.53	5	5
WNT5A	0.023	0.041	0.23	9	-0.42	2	11
WNT11	0.007	0.11	0.24	10	-0.53	18	28
CDC42	-0.005	0.069	0.23	3	-0.28	19	22

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.008	0.067	0.36	1	-0.55	6	7
PDGF/PDGFRA/CRKL	0.019	0.045	0.25	1	-0.39	4	5
positive regulation of JUN kinase activity	0.042	0.044	-10000	0	-0.3	6	6
CRKL	0.021	0.006	-10000	0	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.043	0.15	0.25	1	-0.39	74	75
AP1	-0.11	0.3	0.3	2	-0.92	60	62
mol:IP3	-0.015	0.04	0.3	1	-0.39	3	4
PLCG1	-0.015	0.04	0.3	1	-0.39	3	4
PDGF/PDGFRA/alphaV Integrin	0.019	0.052	0.25	1	-0.39	6	7
RAPGEF1	0.022	0.003	-10000	0	-10000	0	0
CRK	0.021	0.005	-10000	0	-10000	0	0
mol:Ca2+	-0.015	0.039	0.3	1	-0.39	3	4
CAV3	-0.081	0.18	-10000	0	-0.53	68	68
CAV1	-0.12	0.24	-10000	0	-0.53	127	127
SHC/Grb2/SOS1	0.044	0.045	-10000	0	-0.3	6	6
PDGF/PDGFRA/Shf	0.02	0.051	0.25	1	-0.39	6	7
FOS	-0.12	0.29	-10000	0	-0.9	60	60
JUN	-0.022	0.025	-10000	0	-10000	0	0
oligodendrocyte development	0.019	0.051	0.25	1	-0.39	6	7
GRB2	0.022	0.004	-10000	0	-10000	0	0
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
mol:DAG	-0.015	0.04	0.3	1	-0.39	3	4
PDGF/PDGFRA	0.008	0.067	0.36	1	-0.55	6	7
actin cytoskeleton reorganization	0.018	0.051	0.25	1	-0.38	6	7
SRF	-0.005	0.014	-10000	0	-10000	0	0
SHC1	0.022	0.005	-10000	0	-10000	0	0
PI3K	0.016	0.044	0.24	1	-0.33	5	6
PDGF/PDGFRA/Crk/C3G	0.029	0.047	0.24	1	-0.32	6	7
JAK1	-0.013	0.042	0.28	1	-0.39	5	6
ELK1/SRF	-0.01	0.051	0.24	2	-0.31	2	4
SHB	0.021	0.007	-10000	0	-10000	0	0
SHF	0.022	0.003	-10000	0	-10000	0	0
CSNK2A1	0.024	0.02	-10000	0	-10000	0	0
GO:0007205	-0.013	0.045	0.3	1	-0.37	5	6
SOS1	0.022	0.004	-10000	0	-10000	0	0
Ras protein signal transduction	0.042	0.044	-10000	0	-0.3	6	6
PDGF/PDGFRA/SHB	0.019	0.051	0.25	1	-0.39	6	7
PDGF/PDGFRA/Caveolin-1	-0.087	0.19	0.25	1	-0.4	130	131
ITGAV	0.022	0.004	-10000	0	-10000	0	0
ELK1	-0.019	0.046	0.23	1	-0.34	5	6
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
PDGF/PDGFRA/Crk	0.019	0.05	0.25	1	-0.38	6	7
JAK-STAT cascade	-0.013	0.042	0.28	1	-0.39	5	6
cell proliferation	0.02	0.051	0.25	1	-0.38	6	7

×

Syndecan-3-mediated 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.019	0.008	-10000	0	-10000	0	0
Syndecan-3/Src/Cortactin	0.028	0.077	-10000	0	-0.35	9	9
Syndecan-3/Neurocan	0.026	0.071	-10000	0	-0.37	9	9
POMC	0.037	0.081	0.24	43	-0.53	4	47
EGFR	0.023	0.081	0.36	12	-0.53	6	18
Syndecan-3/EGFR	0.019	0.07	0.29	3	-0.37	8	11
AGRP	-0.24	0.26	-10000	0	-0.53	218	218
NCSTN	0.022	0.005	-10000	0	-10000	0	0
PSENEN	0.021	0.007	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
APH1B	0.023	0.002	-10000	0	-10000	0	0
APH1A	0.021	0.006	-10000	0	-10000	0	0
NCAN	0.029	0.059	0.23	35	-10000	0	35
long-term memory	0.026	0.064	-10000	0	-0.36	10	10
Syndecan-3/IL8	0.02	0.069	-10000	0	-0.37	10	10
PSEN1	0.022	0.005	-10000	0	-10000	0	0
Src/Cortactin	0.028	0.013	-10000	0	-10000	0	0
FYN	0.021	0.025	-10000	0	-0.53	1	1
limb bud formation	0.001	0.055	-10000	0	-0.38	10	10
MC4R	0.024	0.049	0.24	21	-10000	0	21
SRC	0.022	0.004	-10000	0	-10000	0	0
PTN	0.011	0.083	0.23	3	-0.53	11	14
FGFR/FGF/Syndecan-3	0.001	0.056	-10000	0	-0.39	10	10
neuron projection morphogenesis	0.029	0.092	0.27	10	-0.35	8	18
Syndecan-3/AgRP	-0.11	0.15	-10000	0	-0.42	10	10
Syndecan-3/AgRP/MC4R	-0.095	0.16	0.32	1	-0.37	15	16
Fyn/Cortactin	0.028	0.023	-10000	0	-0.39	1	1
SDC3	0.001	0.056	-10000	0	-0.39	10	10
GO:0007205	0	0	-10000	0	-10000	0	0
positive regulation of leukocyte migration	0.02	0.068	-10000	0	-0.36	10	10
IL8	0.025	0.058	0.25	14	-0.53	3	17
Syndecan-3/Fyn/Cortactin	0.026	0.065	-10000	0	-0.36	10	10
Syndecan-3/CASK	-0.001	0.056	-10000	0	-0.37	10	10
alpha-MSH/MC4R	0.047	0.066	0.28	6	-0.4	4	10
Gamma Secretase	0.055	0.027	-10000	0	-10000	0	0

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.027	0.044	-10000	0	-0.39	5	5
Necdin/E2F1	0.026	0.048	-10000	0	-0.39	6	6
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.058	0.073	-10000	0	-0.3	13	13
NGF (dimer)/p75(NTR)/BEX1	0.015	0.13	0.28	5	-0.34	51	56
NT-4/5 (dimer)/p75(NTR)	0.039	0.07	0.27	3	-0.39	8	11
IKBKB	0.021	0.017	0.38	1	-10000	0	1
AKT1	0.051	0.1	0.32	5	-0.3	6	11
IKBKG	0.022	0.004	-10000	0	-10000	0	0
BDNF	-0.045	0.18	-10000	0	-0.53	60	60
MGDIs/NGR/p75(NTR)/LINGO1	0.062	0.06	0.3	8	-0.34	1	9
FURIN	0.022	0.003	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	0.002	0.14	0.25	2	-0.34	64	66
LINGO1	0.041	0.06	0.23	43	-10000	0	43
Sortilin/TRAF6/NRIF	0.022	0.031	-10000	0	-0.28	4	4
proBDNF (dimer)	-0.044	0.18	-10000	0	-0.53	60	60
NTRK1	0.016	0.056	-10000	0	-0.53	5	5
RTN4R	0.02	0.027	0.23	1	-0.53	1	2
neuron apoptosis	-0.044	0.14	0.29	2	-0.54	17	19
IRAK1	0.022	0.004	-10000	0	-10000	0	0
SHC1	-0.019	0.048	0.23	3	-0.35	8	11
ARHGDIA	0.022	0.004	-10000	0	-10000	0	0
RhoA/GTP	0.015	0.005	-10000	0	-10000	0	0
Gamma Secretase	0.055	0.027	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.053	0.073	0.25	2	-0.31	13	15
MAGEH1	0.022	0.003	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	0.048	0.086	0.25	3	-0.33	18	21
Mammalian IAPs/DIABLO	0.051	0.042	-10000	0	-0.31	6	6
proNGF (dimer)	0.013	0.077	0.28	3	-0.53	9	12
MAGED1	0.022	0.004	-10000	0	-10000	0	0
APP	0.022	0.005	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.013	0.07	-10000	0	-0.53	8	8
ZNF274	0.022	0.005	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	0.016	0.049	-10000	0	-0.3	8	8
NGF	0.013	0.077	0.28	3	-0.53	9	12
cell cycle arrest	-0.016	0.066	0.21	7	-0.28	13	20
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.014	0.047	-10000	0	-0.25	8	8
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.049	0.063	0.25	2	-0.34	8	10
NCSTN	0.022	0.005	-10000	0	-10000	0	0
mol:GTP	0.046	0.065	0.25	3	-0.34	8	11
PSENEN	0.021	0.007	-10000	0	-10000	0	0
mol:ceramide	-0.022	0.056	0.18	9	-0.31	13	22
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.01	0.038	0.24	1	-0.32	1	2
p75(NTR)/beta APP	0.044	0.042	0.27	3	-10000	0	3
BEX1	-0.02	0.17	0.23	22	-0.53	44	66
mol:GDP	-0.016	0.048	0.22	3	-0.34	8	11
NGF (dimer)	0.042	0.079	-10000	0	-0.33	17	17
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.071	0.059	0.33	5	-0.31	1	6
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
RAC1/GTP	0.04	0.057	0.22	3	-0.3	8	11
MYD88	0.021	0.006	-10000	0	-10000	0	0
CHUK	0.022	0.005	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	0.046	0.066	0.25	3	-0.35	8	11
RHOB	0.022	0.004	-10000	0	-10000	0	0
RHOA	0.021	0.007	-10000	0	-10000	0	0
MAGE-G1/E2F1	0.032	0.009	-10000	0	-10000	0	0
NT3 (dimer)	0.014	0.067	0.23	2	-0.53	7	9
TP53	-0.046	0.11	0.38	4	-0.29	58	62
PRDM4	-0.022	0.056	0.18	9	-0.31	13	22
BDNF (dimer)	0.062	0.18	0.3	15	-0.34	66	81
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
SORT1	0.016	0.055	-10000	0	-0.53	5	5
activation of caspase activity	0.052	0.07	-10000	0	-0.3	13	13
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.053	0.073	0.25	3	-0.31	13	16
RHOC	0.022	0.005	-10000	0	-10000	0	0
XIAP	0.022	0.003	-10000	0	-10000	0	0
MAPK10	-0.031	0.1	0.32	6	-0.4	8	14
DIABLO	0.023	0.002	-10000	0	-10000	0	0
SMPD2	-0.022	0.056	0.18	9	-0.31	13	22
APH1B	0.023	0.002	-10000	0	-10000	0	0
APH1A	0.021	0.006	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	0.043	0.076	0.25	3	-0.34	13	16
PSEN1	0.022	0.005	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.032	0.007	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	0.036	0.065	0.27	1	-0.39	7	8
MAPK8	-0.027	0.096	0.31	7	-0.4	4	11
MAPK9	-0.028	0.095	0.36	4	-0.37	6	10
APAF1	0.023	0.002	-10000	0	-10000	0	0
NTF3	0.014	0.067	0.23	2	-0.53	7	9
NTF4	0.013	0.07	-10000	0	-0.53	8	8
NDN	0.014	0.065	-10000	0	-0.53	7	7
RAC1/GDP	0.016	0.003	-10000	0	-10000	0	0
RhoA-B-C/GDP	0.052	0.057	-10000	0	-0.28	8	8
p75 CTF/Sortilin/TRAF6/NRIF	0.049	0.039	-10000	0	-0.31	4	4
RhoA-B-C/GTP	0.045	0.065	0.25	3	-0.34	8	11
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.021	0.13	-10000	0	-0.3	64	64
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.015	0.13	0.25	2	-0.32	64	66
PRKACB	0.022	0.004	-10000	0	-10000	0	0
proBDNF (dimer)/p75 ECD	-0.019	0.14	-10000	0	-0.39	59	59
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.015	0.061	-10000	0	-0.53	6	6
BIRC2	0.022	0.004	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.004	0.071	0.23	3	-0.3	13	16
BAD	-0.03	0.099	0.32	6	-0.38	5	11
RIPK2	0.022	0.005	-10000	0	-10000	0	0
NGFR	0.041	0.062	0.24	43	-10000	0	43
CYCS	-0.021	0.054	-10000	0	-0.3	12	12
ADAM17	0.022	0.004	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.055	0.065	0.25	3	-0.32	8	11
BCL2L11	-0.029	0.098	0.33	5	-0.38	5	10
BDNF (dimer)/p75(NTR)	-0.009	0.15	0.27	2	-0.4	60	62
PI3K	0.03	0.062	0.25	1	-0.32	6	7
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.053	0.074	0.25	3	-0.31	13	16
NDNL2	0.022	0.004	-10000	0	-10000	0	0
YWHAE	0.022	0.005	-10000	0	-10000	0	0
PRKCI	0.013	0.011	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	0.036	0.072	0.27	3	-0.38	9	12
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.053	0.074	0.25	3	-0.31	13	16
TRAF6	0.022	0.004	-10000	0	-10000	0	0
RAC1	0.022	0.004	-10000	0	-10000	0	0
PRKCZ	0.022	0.005	-10000	0	-10000	0	0
PLG	-0.004	0.03	0.23	5	-10000	0	5
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.029	0.11	0.21	2	-0.3	70	72
SQSTM1	0.021	0.006	-10000	0	-10000	0	0
NGFRAP1	0.022	0.003	-10000	0	-10000	0	0
CASP3	-0.03	0.097	0.29	7	-0.33	9	16
E2F1	0.022	0.005	-10000	0	-10000	0	0
CASP9	0.022	0.005	-10000	0	-10000	0	0
IKK complex	0.046	0.078	-10000	0	-0.33	8	8
NGF (dimer)/TRKA	0.019	0.073	0.27	1	-0.39	14	15
MMP7	0.021	0.087	0.23	22	-0.53	9	31
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.059	0.072	-10000	0	-0.3	13	13
MMP3	0.14	0.11	0.23	293	-0.3	4	297
APAF-1/Caspase 9	-0.035	0.046	-10000	0	-0.46	1	1

×

Ephrin B reverse 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
EFNB2	0.02	0.025	-10000	0	-0.53	1	1
EPHB2	0.025	0.027	0.23	8	-10000	0	8
EFNB1	-0.005	0.013	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.062	0.054	0.28	1	-0.28	1	2
Ephrin B2/EPHB1-2	0.051	0.058	0.24	16	-0.31	2	18
neuron projection morphogenesis	0.043	0.042	0.21	1	-0.26	1	2
Ephrin B1/EPHB1-2/Tiam1	0.058	0.058	0.24	18	-0.29	1	19
DNM1	0.024	0.014	0.23	2	-10000	0	2
cell-cell signaling	0	0.004	-10000	0	-10000	0	0
MAP2K4	-0.02	0.1	0.24	1	-0.43	26	27
YES1	-0.023	0.15	-10000	0	-0.66	27	27
Ephrin B1/EPHB1-2/NCK2	0.059	0.058	0.24	18	-0.29	1	19
PI3K	0	0.091	-10000	0	-0.43	16	16
mol:GDP	0.056	0.057	0.24	16	-0.29	1	17
ITGA2B	0.006	0.092	-10000	0	-0.53	14	14
endothelial cell proliferation	0.026	0.019	-10000	0	-0.33	1	1
FYN	-0.022	0.15	-10000	0	-0.66	27	27
MAP3K7	-0.021	0.11	0.23	1	-0.46	27	28
FGR	-0.03	0.16	-10000	0	-0.68	26	26
TIAM1	0.021	0.025	-10000	0	-0.53	1	1
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
RGS3	0.022	0.004	-10000	0	-10000	0	0
cell adhesion	-0.016	0.096	-10000	0	-0.42	16	16
LYN	-0.023	0.15	-10000	0	-0.66	27	27
Ephrin B1/EPHB1-2/Src Family Kinases	-0.023	0.14	-10000	0	-0.59	27	27
Ephrin B1/EPHB1-2	-0.02	0.11	-10000	0	-0.5	25	25
SRC	-0.02	0.15	-10000	0	-0.64	27	27
ITGB3	0.01	0.082	-10000	0	-0.53	11	11
EPHB1	0.05	0.09	0.28	61	-0.53	1	62
EPHB4	0.021	0.005	-10000	0	-10000	0	0
RAC1	0.022	0.004	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.027	0.019	-10000	0	-0.33	1	1
alphaIIb/beta3 Integrin	0.012	0.093	-10000	0	-0.39	25	25
BLK	-0.025	0.15	-10000	0	-0.66	26	26
HCK	-0.022	0.15	-10000	0	-0.64	27	27
regulation of stress fiber formation	-0.057	0.057	0.29	1	-0.24	16	17
MAPK8	-0.02	0.094	-10000	0	-0.41	25	25
Ephrin B1/EPHB1-2/RGS3	0.059	0.058	0.25	5	-0.29	1	6
endothelial cell migration	-0.009	0.096	0.3	2	-0.37	25	27
NCK2	0.023	0.002	-10000	0	-10000	0	0
PTPN13	0.018	0.052	-10000	0	-0.64	3	3
regulation of focal adhesion formation	-0.057	0.057	0.29	1	-0.24	16	17
chemotaxis	-0.057	0.057	0.29	1	-0.26	2	3
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
Rac1/GTP	0.054	0.048	0.25	1	-0.27	1	2
angiogenesis	-0.02	0.11	-10000	0	-0.49	26	26
LCK	-0.019	0.15	-10000	0	-0.66	26	26

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.012	0.12	0.61	1	-0.41	23	24
IKBKB	0.026	0.082	0.34	6	-0.3	5	11
AKT1	0.049	0.11	0.25	60	-0.24	10	70
IKBKG	0.024	0.074	0.31	5	-0.3	4	9
CALM1	-0.006	0.096	0.28	2	-0.41	15	17
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
MAP3K1	-0.007	0.15	0.69	1	-0.53	22	23
MAP3K7	0.023	0.002	-10000	0	-10000	0	0
mol:Ca2+	-0.006	0.098	0.27	1	-0.4	18	19
DOK1	0.022	0.004	-10000	0	-10000	0	0
AP-1	-0.017	0.082	0.33	3	-0.26	13	16
LYN	0.02	0.035	-10000	0	-0.53	2	2
BLNK	0.021	0.025	-10000	0	-0.53	1	1
SHC1	0.022	0.005	-10000	0	-10000	0	0
BCR complex	0.019	0.09	0.33	1	-0.43	17	18
CD22	-0.039	0.16	0.26	1	-0.59	29	30
CAMK2G	-0.007	0.092	0.3	3	-0.38	15	18
CSNK2A1	0.022	0.005	-10000	0	-10000	0	0
INPP5D	0.021	0.025	-10000	0	-0.53	1	1
SHC/GRB2/SOS1	0.014	0.063	-10000	0	-0.32	13	13
GO:0007205	-0.008	0.1	0.27	1	-0.42	19	20
SYK	0.022	0.004	-10000	0	-10000	0	0
ELK1	-0.01	0.1	0.25	2	-0.4	18	20
NFATC1	-0.016	0.11	0.44	2	-0.47	15	17
B-cell antigen/BCR complex	0.019	0.09	0.33	1	-0.43	17	18
PAG1/CSK	0.027	0.047	-10000	0	-0.39	6	6
NFKBIB	0.022	0.046	0.18	6	-0.13	16	22
HRAS	-0.008	0.095	0.32	3	-0.39	15	18
NFKBIA	0.022	0.046	0.18	6	-0.12	17	23
NF-kappa-B/RelA/I kappa B beta	0.026	0.04	0.18	6	-10000	0	6
RasGAP/Csk	0.043	0.085	0.3	1	-0.34	19	20
mol:GDP	-0.01	0.1	0.26	1	-0.41	19	20
PTEN	0.02	0.007	-10000	0	-10000	0	0
CD79B	0.018	0.051	0.23	1	-0.53	4	5
NF-kappa-B/RelA/I kappa B alpha	0.026	0.04	0.18	6	-10000	0	6
GRB2	0.022	0.004	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.011	0.14	0.58	1	-0.52	23	24
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
mol:IP3	-0.008	0.097	0.28	1	-0.42	17	18
CSK	0.023	0.002	-10000	0	-10000	0	0
FOS	-0.038	0.13	0.31	3	-0.41	23	26
CHUK	0.014	0.09	0.37	3	-0.29	16	19
IBTK	0.023	0.003	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	0.011	0.096	-10000	0	-0.38	14	14
PTPN6	-0.038	0.15	0.25	1	-0.59	25	26
RELA	0.023	0.002	-10000	0	-10000	0	0
BCL2A1	0.017	0.034	0.31	1	-0.13	1	2
VAV2	-0.015	0.13	-10000	0	-0.62	16	16
ubiquitin-dependent protein catabolic process	0.024	0.046	0.18	6	-0.12	16	22
BTK	-0.093	0.33	-10000	0	-1.1	50	50
CD19	-0.021	0.12	0.26	2	-0.52	21	23
MAP4K1	0.016	0.05	-10000	0	-0.53	4	4
CD72	0.021	0.012	0.23	1	-10000	0	1
PAG1	0.015	0.061	-10000	0	-0.53	6	6
MAPK14	-0.005	0.12	0.46	2	-0.46	20	22
SH3BP5	0.014	0.061	-10000	0	-0.53	6	6
PIK3AP1	-0.007	0.11	0.29	1	-0.48	19	20
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.012	0.15	-10000	0	-0.62	20	20
RAF1	-0.009	0.087	0.34	2	-0.36	14	16
RasGAP/p62DOK/SHIP	0.042	0.084	-10000	0	-0.36	16	16
CD79A	0.008	0.1	0.23	9	-0.53	16	25
re-entry into mitotic cell cycle	-0.017	0.082	0.33	3	-0.26	13	16
RASA1	0.021	0.006	-10000	0	-10000	0	0
MAPK3	-0.011	0.076	0.41	1	-0.35	8	9
MAPK1	-0.004	0.084	0.35	5	-0.37	6	11
CD72/SHP1	-0.007	0.15	0.29	6	-0.56	23	29
NFKB1	0.022	0.005	-10000	0	-10000	0	0
MAPK8	-0.005	0.12	0.66	1	-0.46	20	21
actin cytoskeleton organization	-0.011	0.11	0.29	1	-0.56	13	14
NF-kappa-B/RelA	0.052	0.077	0.31	6	-10000	0	6
Calcineurin	0.014	0.092	0.27	1	-0.42	8	9
PI3K	-0.019	0.093	-10000	0	-0.42	17	17
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	0.001	0.093	0.25	3	-0.42	16	19
SOS1	0.022	0.004	-10000	0	-10000	0	0
Bam32/HPK1	-0.014	0.19	-10000	0	-0.69	30	30
DAPP1	-0.031	0.21	-10000	0	-0.77	30	30
cytokine secretion	-0.014	0.1	0.43	2	-0.43	15	17
mol:DAG	-0.008	0.097	0.28	1	-0.42	17	18
PLCG2	0.022	0.005	-10000	0	-10000	0	0
MAP2K1	-0.011	0.082	0.43	1	-0.35	12	13
B-cell antigen/BCR complex/FcgammaRIIB	0.027	0.09	0.31	1	-0.39	19	20
mol:PI-3-4-5-P3	0.002	0.084	0.24	1	-0.33	11	12
ETS1	-0.013	0.094	0.28	3	-0.37	19	22
B-cell antigen/BCR complex/LYN/SYK/BLNK	0.045	0.084	0.3	1	-0.34	18	19
B-cell antigen/BCR complex/LYN	-0.013	0.13	0.27	2	-0.53	22	24
MALT1	0.022	0.005	-10000	0	-10000	0	0
TRAF6	0.022	0.004	-10000	0	-10000	0	0
RAC1	-0.013	0.12	-10000	0	-0.61	13	13
B-cell antigen/BCR complex/LYN/SYK	0.011	0.16	0.34	2	-0.53	27	29
CARD11	-0.008	0.1	0.3	3	-0.43	17	20
FCGR2B	0.015	0.061	-10000	0	-0.53	6	6
PPP3CA	0.022	0.005	-10000	0	-10000	0	0
BCL10	0.022	0.004	-10000	0	-10000	0	0
IKK complex	0.027	0.053	0.17	25	-0.12	3	28
PTPRC	-0.012	0.13	-10000	0	-0.53	31	31
PDPK1	0.028	0.099	0.23	44	-0.24	8	52
PPP3CB	0.022	0.005	-10000	0	-10000	0	0
PPP3CC	0.02	0.007	-10000	0	-10000	0	0
POU2F2	0.02	0.031	0.27	2	-10000	0	2

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.009	0.063	-10000	0	-0.3	10	10
NF kappa B1 p50/RelA/I kappa B alpha	0.007	0.074	0.35	3	-10000	0	3
alphaV/beta3 Integrin/Osteopontin/Src	0.1	0.081	0.27	1	-0.2	5	6
AP1	0.002	0.12	0.3	1	-0.45	4	5
ILK	-0.017	0.064	0.34	1	-0.32	10	11
bone resorption	-0.017	0.06	-10000	0	-0.3	5	5
PTK2B	0.021	0.007	-10000	0	-10000	0	0
PYK2/p130Cas	0.095	0.095	0.28	2	-0.29	10	12
ITGAV	0.024	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.031	0.02	-10000	0	-0.39	1	1
alphaV/beta3 Integrin/Osteopontin	0.1	0.099	0.26	1	-0.35	10	11
MAP3K1	-0.017	0.064	0.34	1	-0.32	10	11
JUN	0.022	0.005	-10000	0	-10000	0	0
MAPK3	-0.02	0.059	0.38	1	-0.3	10	11
MAPK1	-0.02	0.058	0.38	1	-0.3	10	11
Rac1/GDP	0.016	0.003	-10000	0	-10000	0	0
NFKB1	0.022	0.005	-10000	0	-10000	0	0
MAPK8	-0.026	0.057	0.24	3	-0.31	10	13
ITGB3	0.012	0.082	-10000	0	-0.53	11	11
NFKBIA	-0.011	0.058	0.41	2	-0.31	6	8
FOS	-0.043	0.18	-10000	0	-0.53	58	58
CD44	0.021	0.025	-10000	0	-0.53	1	1
CHUK	0.022	0.005	-10000	0	-10000	0	0
PLAU	0	0.072	0.44	2	-10000	0	2
NF kappa B1 p50/RelA	0.007	0.077	-10000	0	-10000	0	0
BCAR1	0.022	0.005	-10000	0	-10000	0	0
RELA	0.023	0.002	-10000	0	-10000	0	0
alphaV beta3 Integrin	0.028	0.061	-10000	0	-0.39	10	10
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	-0.019	0.063	0.34	1	-0.32	10	11
VAV3	-0.028	0.061	0.24	6	-0.33	10	16
MAP3K14	-0.018	0.062	-10000	0	-0.32	10	10
ROCK2	0.022	0.004	-10000	0	-10000	0	0
SPP1	0.12	0.12	0.23	246	-0.3	6	252
RAC1	0.022	0.004	-10000	0	-10000	0	0
Rac1/GTP	-0.018	0.06	0.33	1	-0.3	10	11
MMP2	-0.048	0.099	0.29	2	-0.61	4	6

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.02	0.025	-10000	0	-0.53	1	1
Jak2/Leptin Receptor	-0.017	0.15	-10000	0	-0.43	39	39
PTP1B/AKT1	0.002	0.084	0.26	1	-0.32	18	19
FYN	0.021	0.025	-10000	0	-0.53	1	1
p210 bcr-abl/PTP1B	-0.009	0.088	0.24	2	-0.32	22	24
EGFR	0.021	0.082	0.36	12	-0.54	6	18
EGF/EGFR	0.005	0.098	0.24	8	-0.32	27	35
CSF1	0.017	0.05	-10000	0	-0.53	4	4
AKT1	0.021	0.007	-10000	0	-10000	0	0
INSR	0.022	0.006	-10000	0	-10000	0	0
PTP1B/N-cadherin	0.005	0.093	0.24	7	-0.32	19	26
Insulin Receptor/Insulin	0.014	0.083	-10000	0	-0.33	11	11
HCK	0.018	0.043	-10000	0	-0.53	3	3
CRK	0.021	0.005	-10000	0	-10000	0	0
TYK2	-0.01	0.085	0.28	3	-0.32	19	22
EGF	0.015	0.069	0.23	3	-0.54	7	10
YES1	0.021	0.006	-10000	0	-10000	0	0
CAV1	-0.044	0.13	0.26	5	-0.39	36	41
TXN	0.022	0.005	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	0.012	0.087	-10000	0	-0.34	14	14
cell migration	0.009	0.088	0.32	22	-0.24	2	24
STAT3	0.022	0.003	-10000	0	-10000	0	0
PRLR	0.019	0.098	0.29	21	-0.53	10	31
ITGA2B	0.007	0.092	-10000	0	-0.54	14	14
CSF1R	0.013	0.065	-10000	0	-0.53	7	7
Prolactin Receptor/Prolactin	0.026	0.075	0.28	9	-0.39	10	19
FGR	-0.014	0.14	-10000	0	-0.53	32	32
PTP1B/p130 Cas	0.004	0.085	0.25	1	-0.31	19	20
Crk/p130 Cas	0.013	0.087	0.25	1	-0.32	14	15
DOK1	-0.009	0.1	0.37	1	-0.36	24	25
JAK2	-0.016	0.14	0.27	2	-0.44	42	44
Jak2/Leptin Receptor/Leptin	0.031	0.11	0.28	1	-0.4	13	14
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
PTPN1	-0.009	0.088	0.24	2	-0.32	22	24
LYN	0.02	0.035	-10000	0	-0.53	2	2
CDH2	0.032	0.059	0.25	26	-0.53	1	27
SRC	0.013	0.072	-10000	0	-0.63	5	5
ITGB3	0.01	0.082	-10000	0	-0.54	11	11
CAT1/PTP1B	-0.018	0.14	0.24	3	-0.41	37	40
CAPN1	0.022	0.004	-10000	0	-10000	0	0
CSK	0.023	0.002	-10000	0	-10000	0	0
PI3K	0.011	0.064	-10000	0	-0.34	4	4
mol:H2O2	0	0.003	-10000	0	-10000	0	0
STAT3 (dimer)	0.03	0.1	0.25	1	-0.36	13	14
negative regulation of transcription	-0.015	0.14	0.27	2	-0.43	42	44
FCGR2A	0.012	0.074	-10000	0	-0.53	9	9
FER	0.021	0.007	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	0.011	0.093	-10000	0	-0.39	25	25
BLK	0.013	0.088	0.23	12	-0.53	11	23
Insulin Receptor/Insulin/Shc	0.039	0.013	-10000	0	-10000	0	0
RHOA	0.021	0.007	-10000	0	-10000	0	0
LEPR	-0.008	0.12	-10000	0	-0.53	27	27
BCAR1	0.022	0.005	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.022	0.004	-10000	0	-10000	0	0
mol:NADPH	0	0.002	-10000	0	-10000	0	0
TRPV6	-0.015	0.13	-10000	0	-0.42	33	33
PRL	0.003	0.035	0.23	8	-10000	0	8
SOCS3	0.015	0.11	-10000	0	-1.2	4	4
SPRY2	0.019	0.036	-10000	0	-0.54	2	2
Insulin Receptor/Insulin/IRS1	0.04	0.012	-10000	0	-10000	0	0
CSF1/CSF1R	0.007	0.1	0.25	1	-0.37	17	18
Ras protein signal transduction	0.01	0.1	0.57	14	-10000	0	14
IRS1	0.022	0.004	-10000	0	-10000	0	0
INS	0.01	0.015	-10000	0	-10000	0	0
LEP	0.058	0.084	0.23	92	-0.3	1	93
STAT5B	-0.007	0.11	0.31	1	-0.38	26	27
STAT5A	-0.007	0.11	0.31	1	-0.4	24	25
GRB2	0.022	0.004	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.005	0.084	0.25	1	-0.31	19	20
CSN2	0.016	0.063	-10000	0	-10000	0	0
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
LAT	0.003	0.1	-10000	0	-0.49	17	17
YBX1	0.026	0.005	-10000	0	-10000	0	0
LCK	0.021	0.025	-10000	0	-0.53	1	1
SHC1	0.022	0.005	-10000	0	-10000	0	0
NOX4	0.024	0.019	0.3	2	-10000	0	2

×

Effects of Botulinum toxin

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
STX1A	-0.006	0.005	-10000	0	-10000	0	0
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	-0.009	0.12	-10000	0	-0.38	46	46
STXBP1	0.018	0.05	-10000	0	-0.53	4	4
ACh/CHRNA1	0.014	0.05	0.18	9	-0.28	8	17
RAB3GAP2/RIMS1/UNC13B	0.005	0.11	-10000	0	-0.34	43	43
mol:Ca2+	0	0	-10000	0	-10000	0	0
UniProt:P30996	0	0	-10000	0	-10000	0	0
UniProt:Q60393	0	0	-10000	0	-10000	0	0
CST086	0	0	-10000	0	-10000	0	0
RIMS1	-0.031	0.16	0.23	2	-0.53	45	47
mol:ACh	0	0.031	0.088	10	-0.14	10	20
RAB3GAP2	0.022	0.004	-10000	0	-10000	0	0
STX1A/SNAP25/VAMP2	0.001	0.094	-10000	0	-0.27	44	44
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	0.014	0.05	0.18	9	-0.28	8	17
UNC13B	0.018	0.036	-10000	0	-0.53	2	2
CHRNA1	0.02	0.063	0.23	9	-0.53	5	14
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	0.02	0.039	0.18	16	-0.15	3	19
SNAP25	-0.002	0.04	-10000	0	-0.29	9	9
VAMP2	0.003	0.001	-10000	0	-10000	0	0
SYT1	0.029	0.039	0.24	16	-10000	0	16
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.016	0.032	-10000	0	-0.33	4	4
STX1A/SNAP25 fragment 1/VAMP2	0.001	0.094	-10000	0	-0.27	44	44

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.022	0.004	-10000	0	-10000	0	0
EGFR	0.023	0.081	0.36	12	-0.53	6	18
EGF/EGFR	0.005	0.11	-10000	0	-0.31	50	50
EGF/EGFR dimer/SHC/GRB2/SOS1	0.049	0.069	-10000	0	-0.32	12	12
mol:GTP	0	0	-10000	0	-10000	0	0
EDNRA	0.017	0.05	-10000	0	-0.53	4	4
response to oxidative stress	0	0	-10000	0	-10000	0	0
EGF	0.015	0.068	0.23	3	-0.53	7	10
EGF/EGFR dimer/SHC	0.033	0.071	0.25	7	-0.36	12	19
mol:GDP	0.044	0.066	-10000	0	-0.31	12	12
mol:Ca2+	0	0	-10000	0	-10000	0	0
EDN1	-0.025	0.15	-10000	0	-0.53	42	42
GRB2/SOS1	0.032	0.008	-10000	0	-10000	0	0
HRAS/GTP	0.029	0.057	-10000	0	-0.29	12	12
SHC1	0.022	0.005	-10000	0	-10000	0	0
HRAS/GDP	0.042	0.063	-10000	0	-0.3	12	12
FRAP1	-0.017	0.05	0.15	7	-0.3	12	19
EGF/EGFR dimer	0.024	0.078	0.27	8	-0.42	12	20
SOS1	0.022	0.004	-10000	0	-10000	0	0
GRB2	0.022	0.004	-10000	0	-10000	0	0
ETA receptor/Endothelin-1	-0.009	0.12	-10000	0	-0.39	46	46

×

S1P4 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
GNAO1	0.021	0.029	0.23	2	-0.53	1	3
CDC42/GTP	-0.007	0.093	-10000	0	-0.28	36	36
PLCG1	-0.012	0.081	-10000	0	-0.28	30	30
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.021	0.007	-10000	0	-10000	0	0
GNAI3	0.022	0.005	-10000	0	-10000	0	0
G12/G13	0.032	0.008	-10000	0	-10000	0	0
cell migration	-0.007	0.092	-10000	0	-0.27	36	36
S1PR5	0.024	0.035	0.23	7	-0.53	1	8
S1PR4	-0.02	0.15	-10000	0	-0.53	38	38
MAPK3	-0.012	0.08	-10000	0	-0.28	30	30
MAPK1	-0.011	0.077	-10000	0	-0.29	28	28
S1P/S1P5/Gi	0.017	0.035	-10000	0	-0.22	5	5
GNAI1	0.021	0.025	-10000	0	-0.53	1	1
CDC42/GDP	0.016	0.003	-10000	0	-10000	0	0
S1P/S1P5/G12	0.03	0.022	-10000	0	-0.33	1	1
RHOA	-0.026	0.082	0.36	1	-0.28	37	38
S1P/S1P4/Gi	-0.006	0.087	-10000	0	-0.28	37	37
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	0.016	0.056	-10000	0	-0.53	5	5
S1P/S1P4/G12/G13	0.013	0.092	-10000	0	-0.3	37	37
GNA12	0.022	0.004	-10000	0	-10000	0	0
GNA13	0.022	0.003	-10000	0	-10000	0	0
CDC42	0.022	0.004	-10000	0	-10000	0	0

×

Aurora A signaling

Figure S65. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S65. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	-0.02	0.033	-10000	0	-10000	0	0
BIRC5	0.2	0.082	0.23	422	-0.3	1	423
NFKBIA	-0.023	0.026	0.24	1	-10000	0	1
CPEB1	-0.015	0.14	-10000	0	-0.53	33	33
AKT1	-0.022	0.026	0.24	1	-10000	0	1
NDEL1	0.021	0.005	-10000	0	-10000	0	0
Aurora A/BRCA1	-0.018	0.03	-10000	0	-10000	0	0
NDEL1/TACC3	-0.008	0.041	-10000	0	-10000	0	0
GADD45A	0.022	0.004	-10000	0	-10000	0	0
GSK3B	-0.019	0.02	-10000	0	-10000	0	0
PAK1/Aurora A	-0.019	0.035	0.31	1	-10000	0	1
MDM2	0.023	0.016	0.38	1	-10000	0	1
JUB	0	0	-10000	0	-10000	0	0
TPX2	-0.024	0.095	0.3	36	-10000	0	36
TP53	-0.01	0.046	0.22	1	-0.23	18	19
DLG7	-0.021	0.022	0.15	2	-10000	0	2
AURKAIP1	0.022	0.005	-10000	0	-10000	0	0
ARHGEF7	0.021	0.006	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	-0.009	0.044	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.018	0.029	-10000	0	-10000	0	0
AURKA	-0.025	0.029	0.2	2	-10000	0	2
AURKB	0.076	0.057	0.15	15	-0.17	3	18
CDC25B	-0.011	0.023	-10000	0	-0.31	1	1
G2/M transition checkpoint	-0.021	0.022	-10000	0	-10000	0	0
mRNA polyadenylation	-0.037	0.078	-10000	0	-0.31	32	32
Aurora A/CPEB	-0.037	0.078	-10000	0	-0.31	32	32
Aurora A/TACC1/TRAP/chTOG	-0.004	0.046	-10000	0	-10000	0	0
BRCA1	0.022	0.003	-10000	0	-10000	0	0
centrosome duplication	-0.019	0.035	0.31	1	-10000	0	1
regulation of centrosome cycle	-0.008	0.04	-10000	0	-10000	0	0
spindle assembly	-0.004	0.045	-10000	0	-10000	0	0
TDRD7	0.022	0.004	-10000	0	-10000	0	0
Aurora A/RasGAP/Survivin	0.11	0.079	0.27	6	-10000	0	6
CENPA	0.096	0.05	0.16	72	-10000	0	72
Aurora A/PP2A	-0.02	0.033	-10000	0	-10000	0	0
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	-0.011	0.032	0.24	1	-10000	0	1
negative regulation of DNA binding	-0.01	0.046	0.21	1	-0.29	2	3
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.031	0.01	-10000	0	-10000	0	0
RASA1	0.021	0.006	-10000	0	-10000	0	0
Ajuba/Aurora A	-0.021	0.022	-10000	0	-10000	0	0
mitotic prometaphase	-0.02	0.029	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.025	0.029	0.2	2	-10000	0	2
TACC1	0.018	0.026	-10000	0	-0.53	1	1
TACC3	0.021	0.022	0.38	1	-0.3	1	2
Aurora A/Antizyme1	-0.01	0.044	-10000	0	-10000	0	0
Aurora A/RasGAP	-0.017	0.03	-10000	0	-10000	0	0
OAZ1	0.022	0.004	-10000	0	-10000	0	0
RAN	0.023	0.002	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	-0.021	0.019	-10000	0	-10000	0	0
GIT1	0.022	0.003	-10000	0	-10000	0	0
GIT1/beta-PIX/PAK1	0.042	0.017	0.25	1	-10000	0	1
Importin alpha/Importin beta/TPX2	-0.024	0.095	0.3	36	-10000	0	36
PPP2R5D	0.022	0.004	-10000	0	-10000	0	0
Aurora A/TPX2	-0.024	0.082	0.21	32	-10000	0	32
PAK1	0.023	0.016	0.38	1	-10000	0	1
CKAP5	0.022	0.004	-10000	0	-10000	0	0

×

HIF-2-alpha transcription factor network

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
MMP14	0.015	0.12	-10000	0	-0.71	12	12
oxygen homeostasis	0.001	0.009	-10000	0	-10000	0	0
TCEB2	0.022	0.004	-10000	0	-10000	0	0
TCEB1	0.022	0.005	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	0.008	0.13	0.27	5	-0.36	16	21
EPO	0.023	0.16	0.35	2	-0.49	9	11
FIH (dimer)	0.018	0.019	-10000	0	-10000	0	0
APEX1	0.022	0.024	-10000	0	-10000	0	0
SERPINE1	0.008	0.17	0.38	2	-0.53	10	12
FLT1	-0.034	0.22	-10000	0	-0.83	29	29
ADORA2A	-0.003	0.16	0.37	3	-0.51	10	13
germ cell development	0.01	0.17	0.38	2	-0.55	10	12
SLC11A2	0.01	0.17	0.38	2	-0.54	9	11
BHLHE40	0.009	0.17	0.42	1	-0.54	9	10
HIF1AN	0.018	0.019	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	0.02	0.14	0.3	5	-0.4	13	18
ETS1	0.012	0.083	-10000	0	-0.54	10	10
CITED2	-0.002	0.18	-10000	0	-1.1	13	13
KDR	-0.07	0.33	-10000	0	-1	48	48
PGK1	0.01	0.17	0.38	2	-0.54	9	11
SIRT1	0.022	0.005	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF2A/ARNT	0.064	0.22	0.45	2	-0.6	11	13
EPAS1	-0.022	0.12	0.27	6	-0.36	28	34
SP1	0.026	0.003	-10000	0	-10000	0	0
ABCG2	-0.029	0.25	0.42	1	-0.63	58	59
EFNA1	0.007	0.17	-10000	0	-0.53	10	10
FXN	-0.002	0.16	0.48	4	-0.53	8	12
POU5F1	0.01	0.18	0.42	1	-0.57	10	11
neuron apoptosis	-0.062	0.22	0.58	11	-0.44	2	13
EP300	0.022	0.004	-10000	0	-10000	0	0
EGLN3	0.052	0.08	0.23	76	-10000	0	76
EGLN2	0.017	0.02	-10000	0	-10000	0	0
EGLN1	0.018	0.019	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.041	0.015	-10000	0	-10000	0	0
VHL	0.021	0.006	-10000	0	-10000	0	0
ARNT	0.022	0.024	-10000	0	-10000	0	0
SLC2A1	0.008	0.18	0.41	8	-0.5	15	23
TWIST1	0.006	0.17	0.39	8	-0.51	12	20
ELK1	0.024	0.015	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.022	0.15	0.32	1	-0.42	10	11
VEGFA	0.01	0.17	0.42	1	-0.54	9	10
CREBBP	0.022	0.005	-10000	0	-10000	0	0

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	0.017	0.006	-10000	0	-10000	0	0
epithelial cell differentiation	0.044	0.016	-10000	0	-10000	0	0
CYFIP2	0.007	0.089	-10000	0	-0.53	13	13
ENAH	0.006	0.067	0.26	11	-10000	0	11
EGFR	0.023	0.081	0.36	12	-0.53	6	18
EPHA2	0.018	0.043	-10000	0	-0.53	3	3
MYO6	-0.009	0.029	0.34	1	-10000	0	1
CTNNB1	0.021	0.006	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.031	0.06	-10000	0	-0.34	11	11
AQP5	-0.14	0.22	-10000	0	-0.47	148	148
CTNND1	0.023	0.001	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.01	0.025	0.34	1	-10000	0	1
regulation of calcium-dependent cell-cell adhesion	-0.082	0.12	0.34	1	-0.28	134	135
EGF	0.015	0.068	0.23	3	-0.53	7	10
NCKAP1	0.022	0.004	-10000	0	-10000	0	0
AQP3	-0.056	0.16	-10000	0	-0.46	64	64
cortical microtubule organization	0.044	0.016	-10000	0	-10000	0	0
GO:0000145	-0.01	0.024	0.19	5	-10000	0	5
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.048	0.017	-10000	0	-10000	0	0
MLLT4	0.022	0.004	-10000	0	-10000	0	0
ARF6/GDP	-0.019	0.022	-10000	0	-10000	0	0
ARF6	0.022	0.005	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.043	0.037	-10000	0	-0.31	3	3
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.001	0.012	-10000	0	-10000	0	0
PVRL2	0.022	0.004	-10000	0	-10000	0	0
ZYX	-0.01	0.023	-10000	0	-10000	0	0
ARF6/GTP	0.046	0.039	-10000	0	-0.29	3	3
CDH1	0.022	0.005	-10000	0	-10000	0	0
EGFR/EGFR/EGF/EGF	0.031	0.058	-10000	0	-0.3	12	12
RhoA/GDP	0.045	0.016	-10000	0	-10000	0	0
actin cytoskeleton organization	-0.011	0.02	-10000	0	-10000	0	0
IGF-1R heterotetramer	0.022	0.004	-10000	0	-10000	0	0
GIT1	0.022	0.003	-10000	0	-10000	0	0
IGF1R	0.022	0.004	-10000	0	-10000	0	0
IGF1	0.003	0.1	0.23	1	-0.53	18	19
DIAPH1	-0.016	0.16	-10000	0	-0.58	19	19
Wnt receptor signaling pathway	-0.044	0.016	-10000	0	-10000	0	0
RHOA	0.021	0.007	-10000	0	-10000	0	0
RhoA/GTP	-0.019	0.022	-10000	0	-10000	0	0
CTNNA1	0.021	0.006	-10000	0	-10000	0	0
VCL	-0.011	0.02	-10000	0	-10000	0	0
EFNA1	0.022	0.005	-10000	0	-10000	0	0
LPP	-0.008	0.022	0.34	1	-10000	0	1
Ephrin A1/EPHA2	0.036	0.029	-10000	0	-0.28	3	3
SEC6/SEC8	-0.016	0.01	-10000	0	-10000	0	0
MGAT3	-0.083	0.12	0.34	1	-0.28	134	135
HGF/MET	-0.023	0.12	-10000	0	-0.27	89	89
HGF	-0.09	0.22	-10000	0	-0.53	100	100
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.018	0.006	-10000	0	-10000	0	0
actin cable formation	0.046	0.1	0.33	25	-10000	0	25
KIAA1543	-0.01	0.024	0.2	5	-10000	0	5
KIFC3	-0.01	0.027	0.34	1	-10000	0	1
NCK1	0.019	0.008	-10000	0	-10000	0	0
EXOC3	0.018	0.009	-10000	0	-10000	0	0
ACTN1	-0.01	0.028	0.34	1	-10000	0	1
NCK1/GIT1	0.028	0.013	-10000	0	-10000	0	0
mol:GDP	0.044	0.016	-10000	0	-10000	0	0
EXOC4	0.022	0.004	-10000	0	-10000	0	0
STX4	-0.009	0.028	0.34	1	-10000	0	1
PIP5K1C	-0.01	0.026	0.34	1	-10000	0	1
LIMA1	0.023	0.002	-10000	0	-10000	0	0
ABI1	0.022	0.004	-10000	0	-10000	0	0
ROCK1	0.015	0.084	0.31	17	-10000	0	17
adherens junction assembly	-0.014	0.092	0.31	3	-0.65	7	10
IGF-1R heterotetramer/IGF1	0.029	0.058	-10000	0	-0.27	16	16
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.032	0.008	-10000	0	-10000	0	0
MET	0.02	0.039	0.38	1	-0.53	2	3
PLEKHA7	-0.01	0.026	0.34	1	-10000	0	1
mol:GTP	0.041	0.036	-10000	0	-0.31	3	3
establishment of epithelial cell apical/basal polarity	0.024	0.089	0.34	12	-10000	0	12
cortical actin cytoskeleton stabilization	0.017	0.006	-10000	0	-10000	0	0
regulation of cell-cell adhesion	-0.011	0.02	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.018	0.006	-10000	0	-10000	0	0

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.023	0.002	-10000	0	-10000	0	0
PTK2	0.021	0.006	-10000	0	-10000	0	0
CRKL	0.001	0.05	-10000	0	-0.28	15	15
GRB2/SOS1/SHC	0.042	0.014	-10000	0	-10000	0	0
HRAS	0.022	0.004	-10000	0	-10000	0	0
IRS1/Crk	0.01	0.054	-10000	0	-0.28	16	16
IGF-1R heterotetramer/IGF1/PTP1B	0.032	0.063	-10000	0	-0.32	14	14
AKT1	0.055	0.095	0.22	19	-0.25	5	24
BAD	0.049	0.091	0.21	18	-10000	0	18
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.001	0.052	-10000	0	-0.28	16	16
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.015	0.056	-10000	0	-0.28	16	16
RAF1	0.054	0.11	0.28	12	-0.43	9	21
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.04	0.059	-10000	0	-0.27	15	15
YWHAZ	0.022	0.005	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.018	0.06	-10000	0	-0.3	16	16
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
RPS6KB1	0.056	0.097	0.22	22	-0.25	5	27
GNB2L1	0.021	0.006	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	0.052	0.1	0.27	18	-0.34	4	22
PXN	0.023	0.002	-10000	0	-10000	0	0
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.032	0.008	-10000	0	-10000	0	0
HRAS/GTP	0.017	0.046	-10000	0	-0.25	12	12
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.051	0.057	-10000	0	-0.26	12	12
IGF-1R heterotetramer	0.02	0.021	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	0.03	0.058	-10000	0	-0.28	15	15
Crk/p130 Cas/Paxillin	0.036	0.057	-10000	0	-0.26	15	15
IGF1R	0.02	0.021	-10000	0	-10000	0	0
IGF1	0.005	0.11	0.26	1	-0.54	18	19
IRS2/Crk	0.007	0.054	-10000	0	-0.27	17	17
PI3K	0.022	0.045	-10000	0	-0.27	5	5
apoptosis	-0.053	0.092	-10000	0	-0.26	13	13
HRAS/GDP	0.016	0.003	-10000	0	-10000	0	0
PRKCD	-0.002	0.067	-10000	0	-0.35	16	16
RAF1/14-3-3 E	0.053	0.12	0.28	11	-0.37	11	22
BAD/14-3-3	0.056	0.096	0.28	14	-10000	0	14
PRKCZ	0.054	0.096	0.22	18	-0.25	5	23
Crk/p130 Cas/Paxillin/FAK1	0.052	0.062	-10000	0	-10000	0	0
PTPN1	0.022	0.004	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.003	0.076	-10000	0	-0.38	17	17
BCAR1	0.022	0.005	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.042	0.056	-10000	0	-0.28	12	12
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.022	0.004	-10000	0	-10000	0	0
IRS1/NCK2	0.018	0.057	-10000	0	-0.28	15	15
GRB10	0.022	0.005	-10000	0	-10000	0	0
PTPN11	0.001	0.052	-10000	0	-0.28	16	16
IRS1	0.004	0.059	-10000	0	-0.3	16	16
IRS2	0	0.054	-10000	0	-0.28	17	17
IGF-1R heterotetramer/IGF1	0.018	0.08	-10000	0	-0.41	16	16
GRB2	0.022	0.004	-10000	0	-10000	0	0
PDPK1	0.056	0.098	0.17	193	-0.26	5	198
YWHAE	0.022	0.005	-10000	0	-10000	0	0
PRKD1	-0.014	0.094	-10000	0	-0.42	18	18
SHC1	0.022	0.005	-10000	0	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.02	0.15	-10000	0	-0.53	17	17
MAP3K8	0.017	0.028	-10000	0	-0.53	1	1
FOS	-0.014	0.12	-10000	0	-0.48	16	16
PRKCA	0.015	0.038	-10000	0	-0.54	2	2
PTPN7	0.016	0.035	0.38	1	-0.53	1	2
HRAS	0.022	0.004	-10000	0	-10000	0	0
PRKCB	-0.011	0.12	-10000	0	-0.53	25	25
NRAS	0.021	0.005	-10000	0	-10000	0	0
RAS family/GTP	0.03	0.026	-10000	0	-10000	0	0
MAPK3	0.001	0.094	-10000	0	-0.6	8	8
MAP2K1	-0.016	0.12	-10000	0	-0.44	29	29
ELK1	0.015	0.02	-10000	0	-10000	0	0
BRAF	-0.012	0.099	-10000	0	-0.42	25	25
mol:GTP	-0.001	0.002	-10000	0	-0.005	60	60
MAPK1	0.001	0.091	-10000	0	-0.5	9	9
RAF1	-0.015	0.11	-10000	0	-0.47	25	25
KRAS	0.021	0.006	-10000	0	-10000	0	0

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.022	0.004	-10000	0	-10000	0	0
SPHK1	0.022	0.004	-10000	0	-10000	0	0
GNAI2	0.021	0.007	-10000	0	-10000	0	0
mol:S1P	0.01	0.003	-10000	0	-10000	0	0
GNAO1	0.021	0.029	0.23	2	-0.53	1	3
mol:Sphinganine-1-P	-0.01	0.002	-10000	0	-10000	0	0
growth factor activity	0	0	-10000	0	-10000	0	0
S1P/S1P2/G12/G13	0.043	0.033	-10000	0	-10000	0	0
GNAI3	0.022	0.005	-10000	0	-10000	0	0
G12/G13	0.032	0.008	-10000	0	-10000	0	0
S1PR3	0.022	0.004	-10000	0	-10000	0	0
S1PR2	0.022	0.004	-10000	0	-10000	0	0
EDG1	0	0	-10000	0	-10000	0	0
S1P1/S1P	0.003	0.025	-10000	0	-0.2	4	4
S1PR5	0.024	0.035	0.23	7	-0.53	1	8
S1PR4	-0.02	0.15	-10000	0	-0.53	38	38
GNAI1	0.021	0.025	-10000	0	-0.53	1	1
S1P/S1P5/G12	0.033	0.037	-10000	0	-0.29	1	1
S1P/S1P3/Gq	-0.051	0.13	-10000	0	-0.28	117	117
S1P/S1P4/Gi	-0.004	0.09	0.26	1	-0.29	33	34
GNAQ	0.021	0.025	-10000	0	-0.53	1	1
GNAZ	0.016	0.056	-10000	0	-0.53	5	5
GNA14	-0.11	0.24	-10000	0	-0.53	117	117
GNA15	0.022	0.004	-10000	0	-10000	0	0
GNA12	0.022	0.004	-10000	0	-10000	0	0
GNA13	0.022	0.003	-10000	0	-10000	0	0
GNA11	0.022	0.004	-10000	0	-10000	0	0
ABCC1	0.023	0.01	0.23	1	-10000	0	1

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.023	0.004	-10000	0	-10000	0	0
HDAC2	0.024	0.002	-10000	0	-10000	0	0
GNB1/GNG2	0.034	0.044	0.25	1	-0.34	6	7
forebrain development	-0.1	0.16	-10000	0	-0.57	18	18
GNAO1	0.015	0.031	0.23	2	-0.54	1	3
SMO/beta Arrestin2	0.007	0.03	0.24	1	-10000	0	1
SMO	0.004	0.032	0.37	2	-10000	0	2
ARRB2	0.005	0.018	-10000	0	-10000	0	0
GLI3/SPOP	0.024	0.092	-10000	0	-0.42	9	9
mol:GTP	-0.003	0.004	-10000	0	-10000	0	0
GSK3B	0.02	0.007	-10000	0	-10000	0	0
GNAI2	0.014	0.013	-10000	0	-10000	0	0
SIN3/HDAC complex	0.055	0.022	-10000	0	-10000	0	0
GNAI1	0.015	0.027	-10000	0	-0.54	1	1
XPO1	0	0.024	-10000	0	-10000	0	0
GLI1/Su(fu)	-0.099	0.16	-10000	0	-0.59	18	18
SAP30	0.022	0.006	-10000	0	-10000	0	0
mol:GDP	0.004	0.032	0.37	2	-10000	0	2
MIM/GLI2A	-0.041	0.069	-10000	0	-10000	0	0
IFT88	0.021	0.006	-10000	0	-10000	0	0
GNAI3	0.016	0.012	-10000	0	-10000	0	0
GLI2	0.015	0.075	0.31	2	-0.37	7	9
GLI3	0.013	0.096	0.41	1	-0.43	10	11
CSNK1D	0.022	0.004	-10000	0	-10000	0	0
CSNK1E	0.022	0.004	-10000	0	-10000	0	0
SAP18	0.022	0.006	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.021	0.006	-10000	0	-10000	0	0
GNG2	0.016	0.055	-10000	0	-0.53	5	5
Gi family/GTP	-0.01	0.05	-10000	0	-0.26	7	7
SIN3B	0.023	0.005	-10000	0	-10000	0	0
SIN3A	0.024	0.003	-10000	0	-10000	0	0
GLI3/Su(fu)	0.011	0.11	-10000	0	-0.43	21	21
GLI2/Su(fu)	0.009	0.087	-10000	0	-0.4	12	12
FOXA2	-0.51	0.55	-10000	0	-1.1	248	248
neural tube patterning	-0.1	0.16	-10000	0	-0.57	18	18
SPOP	0.022	0.003	-10000	0	-10000	0	0
Su(fu)/PIAS1	0.008	0.046	-10000	0	-10000	0	0
GNB1	0.021	0.025	-10000	0	-0.53	1	1
CSNK1G2	0.022	0.004	-10000	0	-10000	0	0
CSNK1G3	0.021	0.006	-10000	0	-10000	0	0
MTSS1	-0.04	0.069	-10000	0	-10000	0	0
embryonic limb morphogenesis	-0.1	0.16	-10000	0	-0.57	18	18
SUFU	0.004	0.016	-10000	0	-10000	0	0
LGALS3	0.022	0.004	-10000	0	-10000	0	0
catabolic process	0.025	0.12	-10000	0	-0.48	15	15
GLI3A/CBP	0.005	0.029	-10000	0	-0.36	1	1
KIF3A	0.021	0.006	-10000	0	-10000	0	0
GLI1	-0.1	0.16	-10000	0	-0.58	18	18
RAB23	0.022	0.004	-10000	0	-10000	0	0
CSNK1A1	0.021	0.006	-10000	0	-10000	0	0
IFT172	0.022	0.003	-10000	0	-10000	0	0
RBBP7	0.023	0.005	-10000	0	-10000	0	0
Su(fu)/Galectin3	0.01	0.041	-10000	0	-10000	0	0
GNAZ	0.01	0.056	-10000	0	-0.54	5	5
RBBP4	0.023	0.004	-10000	0	-10000	0	0
CSNK1G1	0.023	0.002	-10000	0	-10000	0	0
PIAS1	0.023	0.002	-10000	0	-10000	0	0
PRKACA	0.022	0.004	-10000	0	-10000	0	0
GLI2/SPOP	0.022	0.078	0.23	1	-0.38	7	8
STK36	0	0.025	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.01	0.064	-10000	0	-0.33	13	13
PTCH1	-0.1	0.17	-10000	0	-0.74	14	14
MIM/GLI1	-0.22	0.27	-10000	0	-0.5	223	223
CREBBP	0.005	0.029	-10000	0	-0.36	1	1
Su(fu)/SIN3/HDAC complex	0.007	0.088	-10000	0	-0.4	16	16

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.01	0.065	-10000	0	-0.35	15	15
EPHB2	0.025	0.027	0.23	8	-10000	0	8
Syndecan-2/TACI	0.016	0.053	-10000	0	-0.33	10	10
LAMA1	0.082	0.1	0.24	142	-0.42	2	144
Syndecan-2/alpha2 ITGB1	0.032	0.057	-10000	0	-0.29	13	13
HRAS	0.022	0.004	-10000	0	-10000	0	0
Syndecan-2/CASK	0.003	0.033	-10000	0	-0.32	5	5
ITGA5	0.023	0.002	-10000	0	-10000	0	0
BAX	-0.007	0.026	-10000	0	-10000	0	0
EPB41	0.022	0.004	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	0.016	0.032	-10000	0	-0.3	5	5
LAMA3	0.009	0.082	-10000	0	-0.53	11	11
EZR	0.022	0.003	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	0.009	0.082	-10000	0	-0.53	11	11
Syndecan-2/MMP2	0.015	0.05	-10000	0	-0.36	8	8
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.031	0.01	-10000	0	-10000	0	0
dendrite morphogenesis	0.021	0.037	-10000	0	-0.33	4	4
Syndecan-2/GM-CSF	-0.011	0.1	-10000	0	-0.33	44	44
determination of left/right symmetry	0.004	0.039	-10000	0	-0.38	5	5
Syndecan-2/PKC delta	0.017	0.035	-10000	0	-0.32	5	5
GNB2L1	0.021	0.006	-10000	0	-10000	0	0
MAPK3	-0.015	0.094	0.19	14	-0.3	44	58
MAPK1	-0.014	0.089	0.19	11	-0.3	39	50
Syndecan-2/RACK1	0.028	0.032	-10000	0	-0.27	5	5
NF1	0.022	0.004	-10000	0	-10000	0	0
FGFR/FGF/Syndecan-2	0.004	0.039	-10000	0	-0.38	5	5
ITGA2	0.021	0.006	-10000	0	-10000	0	0
MAPK8	0.002	0.03	-10000	0	-0.33	4	4
Syndecan-2/alpha2/beta1 Integrin	0.071	0.076	0.26	12	-0.29	6	18
Syndecan-2/Kininogen	0.015	0.042	0.21	13	-0.33	2	15
ITGB1	0.022	0.004	-10000	0	-10000	0	0
SRC	-0.003	0.041	0.18	17	-0.27	3	20
Syndecan-2/CASK/Protein 4.1	0.016	0.032	-10000	0	-0.3	5	5
extracellular matrix organization	0.018	0.035	-10000	0	-0.32	5	5
actin cytoskeleton reorganization	0.01	0.065	-10000	0	-0.35	15	15
Syndecan-2/Caveolin-2/Ras	0.023	0.058	-10000	0	-0.32	12	12
Syndecan-2/Laminin alpha3	0.01	0.062	-10000	0	-0.34	15	15
Syndecan-2/RasGAP	0.036	0.034	-10000	0	-0.26	5	5
alpha5/beta1 Integrin	0.033	0.007	-10000	0	-10000	0	0
PRKCD	0.021	0.007	-10000	0	-10000	0	0
Syndecan-2 dimer	0.021	0.037	-10000	0	-0.33	4	4
GO:0007205	0.001	0	-10000	0	-10000	0	0
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	0.023	0.027	-10000	0	-0.26	3	3
RHOA	0.021	0.007	-10000	0	-10000	0	0
SDCBP	0.022	0.005	-10000	0	-10000	0	0
TNFRSF13B	0.017	0.062	0.23	8	-0.53	5	13
RASA1	0.021	0.006	-10000	0	-10000	0	0
alpha2/beta1 Integrin	0.031	0.01	-10000	0	-10000	0	0
Syndecan-2/Synbindin	0.018	0.035	-10000	0	-0.33	5	5
TGFB1	0.022	0.005	-10000	0	-10000	0	0
CASP3	0.012	0.04	0.19	16	-0.3	3	19
FN1	0.009	0.085	-10000	0	-0.53	12	12
Syndecan-2/IL8	0.02	0.052	0.25	2	-0.33	8	10
SDC2	0.004	0.039	-10000	0	-0.38	5	5
KNG1	0.007	0.053	0.31	13	-10000	0	13
Syndecan-2/Neurofibromin	0.018	0.035	-10000	0	-0.33	5	5
TRAPPC4	0.022	0.004	-10000	0	-10000	0	0
CSF2	-0.028	0.15	-10000	0	-0.53	42	42
Syndecan-2/TGFB1	0.018	0.035	-10000	0	-0.32	5	5
Syndecan-2/Syntenin/PI-4-5-P2	0.017	0.032	-10000	0	-0.3	5	5
Syndecan-2/Ezrin	0.029	0.034	-10000	0	-0.29	5	5
PRKACA	0.013	0.046	0.19	19	-0.3	5	24
angiogenesis	0.02	0.052	0.25	2	-0.33	8	10
MMP2	0.017	0.05	-10000	0	-0.53	4	4
IL8	0.025	0.058	0.25	14	-0.53	3	17
calcineurin-NFAT signaling pathway	0.016	0.053	-10000	0	-0.33	10	10

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.014	0.14	-10000	0	-0.56	22	22
Syndecan-4/Syndesmos	0.019	0.093	-10000	0	-0.65	5	5
positive regulation of JNK cascade	0.006	0.12	-10000	0	-0.54	11	11
Syndecan-4/ADAM12	0.044	0.12	-10000	0	-0.67	5	5
CCL5	0.012	0.074	-10000	0	-0.53	9	9
Rac1/GDP	0.016	0.003	-10000	0	-10000	0	0
DNM2	0.022	0.004	-10000	0	-10000	0	0
ITGA5	0.023	0.002	-10000	0	-10000	0	0
SDCBP	0.022	0.005	-10000	0	-10000	0	0
PLG	0.013	0.028	0.22	5	-10000	0	5
ADAM12	0.069	0.091	0.23	117	-0.3	2	119
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0.022	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.032	0.019	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	0.051	0.12	0.35	1	-0.64	6	7
Syndecan-4/CXCL12/CXCR4	0.007	0.12	-10000	0	-0.57	11	11
Syndecan-4/Laminin alpha3	0.011	0.095	-10000	0	-0.6	5	5
MDK	0.027	0.033	0.26	9	-10000	0	9
Syndecan-4/FZD7	0.019	0.092	-10000	0	-0.62	5	5
Syndecan-4/Midkine	0.02	0.095	0.36	2	-0.62	5	7
FZD7	0.023	0.016	0.38	1	-10000	0	1
Syndecan-4/FGFR1/FGF	0.015	0.093	-10000	0	-0.59	5	5
THBS1	0.013	0.074	-10000	0	-0.53	9	9
integrin-mediated signaling pathway	0.019	0.093	-10000	0	-0.63	5	5
positive regulation of MAPKKK cascade	0.006	0.12	-10000	0	-0.54	11	11
Syndecan-4/TACI	0.019	0.098	-10000	0	-0.65	5	5
CXCR4	0.021	0.025	-10000	0	-0.53	1	1
cell adhesion	0.005	0.055	0.19	5	-0.3	13	18
Syndecan-4/Dynamin	0.018	0.093	-10000	0	-0.65	5	5
Syndecan-4/TSP1	0.014	0.11	-10000	0	-0.61	10	10
Syndecan-4/GIPC	0.018	0.092	-10000	0	-0.71	4	4
Syndecan-4/RANTES	0.013	0.1	-10000	0	-0.6	7	7
ITGB1	0.022	0.004	-10000	0	-10000	0	0
LAMA1	0.082	0.1	0.24	142	-0.42	2	144
LAMA3	0.009	0.082	-10000	0	-0.53	11	11
RAC1	0.022	0.004	-10000	0	-10000	0	0
PRKCA	0.004	0.1	0.76	9	-0.47	1	10
Syndecan-4/alpha-Actinin	0.019	0.093	-10000	0	-0.66	5	5
TFPI	-0.017	0.14	-10000	0	-0.53	35	35
F2	0.026	0.039	0.23	16	-10000	0	16
alpha5/beta1 Integrin	0.033	0.007	-10000	0	-10000	0	0
positive regulation of cell adhesion	0.014	0.1	0.38	1	-0.57	6	7
ACTN1	0.022	0.004	-10000	0	-10000	0	0
TNC	0.025	0.039	0.23	10	-0.53	1	11
Syndecan-4/CXCL12	-0.003	0.12	-10000	0	-0.59	11	11
FGF6	-0.016	0.006	-10000	0	-10000	0	0
RHOA	0.021	0.007	-10000	0	-10000	0	0
CXCL12	-0.021	0.15	-10000	0	-0.53	39	39
TNFRSF13B	0.017	0.062	0.23	8	-0.53	5	13
FGF2	0.008	0.085	-10000	0	-0.53	12	12
FGFR1	0.017	0.026	-10000	0	-0.53	1	1
Syndecan-4/PI-4-5-P2	0.002	0.088	-10000	0	-0.65	5	5
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.006	0.084	-10000	0	-0.52	12	12
cell migration	-0.018	0.01	-10000	0	-10000	0	0
PRKCD	0.018	0.013	-10000	0	-10000	0	0
vasculogenesis	0.014	0.1	-10000	0	-0.58	10	10
SDC4	0.011	0.08	-10000	0	-0.76	3	3
Syndecan-4/Tenascin C	0.02	0.097	-10000	0	-0.66	5	5
Syndecan-4/PI-4-5-P2/PKC alpha	-0.026	0.015	-10000	0	-10000	0	0
Syndecan-4/Syntenin	0.018	0.091	-10000	0	-0.62	5	5
MMP9	0.034	0.049	0.23	27	-10000	0	27
Rac1/GTP	0.004	0.056	0.19	5	-0.31	13	18
cytoskeleton organization	0.019	0.09	-10000	0	-0.62	5	5
GIPC1	0.022	0.004	-10000	0	-10000	0	0
Syndecan-4/TFPI	0	0.12	-10000	0	-0.66	7	7

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.022	0.006	-10000	0	-10000	0	0
HSPA8	0.022	0.004	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	0.015	0.098	-10000	0	-0.38	22	22
AKT1	0.014	0.031	-10000	0	-10000	0	0
GSC	0.016	0.072	-10000	0	-0.47	2	2
NKX2-5	-0.001	0.015	-10000	0	-0.24	1	1
muscle cell differentiation	-0.033	0.092	0.44	6	-10000	0	6
SMAD2-3/SMAD4/SP1	0.052	0.073	-10000	0	-10000	0	0
SMAD4	0.015	0.039	-10000	0	-10000	0	0
CBFB	0.022	0.005	-10000	0	-10000	0	0
SAP18	0.021	0.006	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.043	0.024	-10000	0	-0.34	1	1
SMAD3/SMAD4/VDR	0.053	0.051	-10000	0	-0.29	1	1
MYC	0.023	0.014	-10000	0	-10000	0	0
CDKN2B	-0.22	0.48	-10000	0	-1.5	53	53
AP1	-0.001	0.1	-10000	0	-0.28	52	52
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.033	0.067	-10000	0	-0.39	4	4
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.014	0.11	-10000	0	-0.34	42	42
SP3	0.024	0.004	-10000	0	-10000	0	0
CREB1	0.022	0.003	-10000	0	-10000	0	0
FOXH1	0.042	0.07	0.27	40	-10000	0	40
SMAD3/SMAD4/GR	0.033	0.048	-10000	0	-10000	0	0
GATA3	0.009	0.091	0.23	2	-0.49	15	17
SKI/SIN3/HDAC complex/NCoR1	0	0.085	-10000	0	-0.41	14	14
MEF2C/TIF2	0.018	0.095	0.31	3	-0.52	10	13
endothelial cell migration	-0.018	0.07	0.75	3	-10000	0	3
MAX	0.021	0.005	-10000	0	-10000	0	0
RBBP7	0.022	0.005	-10000	0	-10000	0	0
RBBP4	0.022	0.004	-10000	0	-10000	0	0
RUNX2	0.022	0.003	-10000	0	-10000	0	0
RUNX3	0.022	0.004	-10000	0	-10000	0	0
RUNX1	0.022	0.005	-10000	0	-10000	0	0
CTBP1	0.021	0.006	-10000	0	-10000	0	0
NR3C1	0.021	0.006	-10000	0	-10000	0	0
VDR	0.021	0.025	-10000	0	-0.53	1	1
CDKN1A	0.013	0.052	-10000	0	-10000	0	0
KAT2B	0.021	0.007	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	0.052	0.067	0.28	4	-0.25	3	7
DCP1A	0.021	0.007	-10000	0	-10000	0	0
SKI	0.022	0.005	-10000	0	-10000	0	0
SERPINE1	0.018	0.071	-10000	0	-0.76	3	3
SMAD3/SMAD4/ATF2	0.035	0.048	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	0.034	0.055	-10000	0	-0.43	2	2
SAP30	0.021	0.006	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.04	0.019	-10000	0	-10000	0	0
JUN	-0.01	0.098	-10000	0	-0.27	50	50
SMAD3/SMAD4/IRF7	0.036	0.05	-10000	0	-10000	0	0
TFE3	0.025	0.006	-10000	0	-10000	0	0
COL1A2	0.026	0.031	-10000	0	-10000	0	0
mesenchymal cell differentiation	-0.035	0.048	-10000	0	-10000	0	0
DLX1	0.14	0.11	0.24	290	-0.3	1	291
TCF3	0.022	0.004	-10000	0	-10000	0	0
FOS	-0.041	0.18	-10000	0	-0.54	58	58
SMAD3/SMAD4/Max	0.033	0.048	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.042	0.014	-10000	0	-10000	0	0
ZBTB17	0.022	0.007	-10000	0	-10000	0	0
LAMC1	0.013	0.034	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.035	0.048	-10000	0	-10000	0	0
IRF7	0.023	0.005	-10000	0	-10000	0	0
ESR1	-0.005	0.12	-10000	0	-0.53	23	23
HNF4A	0.021	0.033	0.25	8	-10000	0	8
MEF2C	0.013	0.098	0.37	4	-0.52	10	14
SMAD2-3/SMAD4	0.034	0.064	-10000	0	-0.25	2	2
Cbp/p300/Src-1	0.043	0.015	-10000	0	-10000	0	0
IGHV3OR16-13	0.006	0.033	-10000	0	-0.35	4	4
TGIF2/HDAC complex	0.022	0.004	-10000	0	-10000	0	0
CREBBP	0.022	0.006	-10000	0	-10000	0	0
SKIL	0.013	0.011	-10000	0	-10000	0	0
HDAC1	0.022	0.004	-10000	0	-10000	0	0
HDAC2	0.023	0.002	-10000	0	-10000	0	0
SNIP1	0.023	0.016	0.38	1	-10000	0	1
GCN5L2	0	0.003	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.041	0.049	-10000	0	-10000	0	0
MSG1/HSC70	0.032	0.021	-10000	0	-0.39	1	1
SMAD2	0.016	0.032	-10000	0	-10000	0	0
SMAD3	0.015	0.036	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.015	0.037	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	-0.003	0.065	0.23	2	-0.41	7	9
NCOR1	0.022	0.005	-10000	0	-10000	0	0
NCOA2	0.021	0.025	-10000	0	-0.53	1	1
NCOA1	0.022	0.003	-10000	0	-10000	0	0
MYOD/E2A	0.048	0.054	0.27	1	-0.2	3	4
SMAD2-3/SMAD4/SP1/MIZ-1	0.059	0.079	-10000	0	-10000	0	0
IFNB1	0.008	0.029	-10000	0	-10000	0	0
SMAD3/SMAD4/MEF2C	0.032	0.1	-10000	0	-0.55	9	9
CITED1	0.021	0.027	0.23	1	-0.53	1	2
SMAD2-3/SMAD4/ARC105	0.041	0.063	-10000	0	-10000	0	0
RBL1	0.022	0.004	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.03	0.16	-10000	0	-0.52	46	46
RUNX1-3/PEBPB2	0.042	0.014	-10000	0	-10000	0	0
SMAD7	0.003	0.099	-10000	0	-10000	0	0
MYC/MIZ-1	0.032	0.023	-10000	0	-10000	0	0
SMAD3/SMAD4	0.013	0.044	-10000	0	-0.43	1	1
IL10	0	0.075	-10000	0	-0.36	15	15
PIASy/HDAC complex	0.019	0.012	-10000	0	-10000	0	0
PIAS3	0.021	0.007	-10000	0	-10000	0	0
CDK2	0.023	0.004	-10000	0	-10000	0	0
IL5	-0.001	0.067	-10000	0	-0.35	7	7
CDK4	0.024	0.017	0.38	1	-10000	0	1
PIAS4	0.019	0.012	-10000	0	-10000	0	0
ATF3	0.02	0.035	-10000	0	-0.53	2	2
SMAD3/SMAD4/SP1	0.041	0.055	-10000	0	-10000	0	0
FOXG1	0.027	0.078	0.24	54	-0.3	1	55
FOXO3	0.001	0.033	-10000	0	-10000	0	0
FOXO1	0.002	0.03	-10000	0	-10000	0	0
FOXO4	0.001	0.032	-10000	0	-10000	0	0
heart looping	0.013	0.097	0.37	4	-0.51	10	14
CEBPB	0.016	0.022	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	0.11	0.094	0.27	6	-10000	0	6
MYOD1	0.03	0.086	0.23	68	-0.3	3	71
SMAD3/SMAD4/HNF4	0.037	0.053	0.27	1	-10000	0	1
SMAD3/SMAD4/GATA3	0.027	0.085	-10000	0	-0.36	16	16
SnoN/SIN3/HDAC complex/NCoR1	0.013	0.011	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.049	0.054	-10000	0	-10000	0	0
SMAD3/SMAD4/SP1-3	0.054	0.056	-10000	0	-10000	0	0
MED15	0.021	0.006	-10000	0	-10000	0	0
SP1	0.023	0.016	-10000	0	-10000	0	0
SIN3B	0.022	0.004	-10000	0	-10000	0	0
SIN3A	0.023	0.002	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.05	0.072	0.26	4	-0.32	8	12
ITGB5	0.014	0.04	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.005	0.072	-10000	0	-0.34	16	16
SMAD3/SMAD4/AR	-0.043	0.16	-10000	0	-0.36	99	99
AR	-0.091	0.22	-10000	0	-0.53	100	100
negative regulation of cell growth	0.013	0.047	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	0.049	0.071	0.27	1	-10000	0	1
E2F5	0.022	0.005	-10000	0	-10000	0	0
E2F4	0.022	0.005	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.063	0.063	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4	-0.014	0.11	-10000	0	-0.37	43	43
TFDP1	0.023	0.028	0.38	3	-10000	0	3
SMAD3/SMAD4/AP1	0.013	0.11	-10000	0	-0.28	52	52
SMAD3/SMAD4/RUNX2	0.035	0.049	-10000	0	-10000	0	0
TGIF2	0.022	0.004	-10000	0	-10000	0	0
TGIF1	0.022	0.005	-10000	0	-10000	0	0
ATF2	0.022	0.004	-10000	0	-10000	0	0

×

LPA receptor mediated 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.035	0.061	-10000	0	-0.39	8	8
NF kappa B1 p50/RelA/I kappa B alpha	-0.001	0.075	-10000	0	-0.36	2	2
AP1	-0.003	0.11	-10000	0	-0.28	61	61
mol:PIP3	-0.017	0.045	-10000	0	-0.3	9	9
AKT1	0.006	0.097	0.32	8	-0.46	2	10
PTK2B	-0.017	0.079	0.18	1	-0.34	13	14
RHOA	-0.014	0.082	-10000	0	-0.31	31	31
PIK3CB	0.019	0.009	-10000	0	-10000	0	0
mol:Ca2+	-0.029	0.064	-10000	0	-0.28	10	10
MAGI3	0.021	0.005	-10000	0	-10000	0	0
RELA	0.023	0.002	-10000	0	-10000	0	0
apoptosis	0.009	0.04	0.19	1	-0.28	8	9
HRAS/GDP	0.016	0.003	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.002	0.094	0.29	5	-0.3	14	19
NF kappa B1 p50/RelA	-0.006	0.076	-10000	0	-0.38	3	3
endothelial cell migration	0.007	0.063	-10000	0	-0.68	4	4
ADCY4	-0.004	0.075	-10000	0	-0.45	6	6
ADCY5	-0.008	0.071	-10000	0	-0.65	2	2
ADCY6	0.007	0.056	-10000	0	-0.38	5	5
ADCY7	0.008	0.052	-10000	0	-0.39	4	4
ADCY1	0.007	0.052	-10000	0	-0.83	1	1
ADCY2	0.002	0.064	0.21	2	-0.44	3	5
ADCY3	0.008	0.054	-10000	0	-0.39	4	4
ADCY8	-0.044	0.1	-10000	0	-0.47	7	7
ADCY9	0.007	0.057	-10000	0	-0.38	6	6
GSK3B	-0.001	0.092	0.2	35	-0.34	10	45
arachidonic acid secretion	0.004	0.06	-10000	0	-0.41	6	6
GNG2	0.016	0.055	-10000	0	-0.53	5	5
TRIP6	0.015	0.007	-10000	0	-10000	0	0
GNAO1	0.01	0.039	-10000	0	-0.35	5	5
HRAS	0.022	0.004	-10000	0	-10000	0	0
NFKBIA	-0.019	0.071	0.22	1	-0.33	7	8
GAB1	0.021	0.006	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	0.008	0.16	-10000	0	-0.82	18	18
JUN	0.022	0.004	-10000	0	-10000	0	0
LPA/LPA2/NHERF2	0.028	0.027	-10000	0	-0.33	2	2
TIAM1	-0.009	0.18	-10000	0	-0.94	18	18
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
mol:IP3	-0.028	0.063	-10000	0	-0.29	9	9
PLCB3	0.011	0.032	0.18	9	-0.3	2	11
FOS	-0.043	0.18	-10000	0	-0.53	58	58
positive regulation of mitosis	0.004	0.06	-10000	0	-0.41	6	6
LPA/LPA1-2-3	0.041	0.052	0.24	1	-0.31	8	9
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0	-10000	0	-10000	0	0
BCAR1	0.022	0.005	-10000	0	-10000	0	0
stress fiber formation	-0.001	0.065	0.35	1	-0.38	6	7
GNAZ	0.007	0.048	-10000	0	-0.33	9	9
EGFR/PI3K-beta/Gab1	0.01	0.052	-10000	0	-0.32	9	9
positive regulation of dendritic cell cytokine production	0.039	0.051	0.24	1	-0.31	8	9
LPA/LPA2/MAGI-3	0.028	0.015	-10000	0	-10000	0	0
ARHGEF1	0.009	0.046	-10000	0	-0.51	1	1
GNAI2	0.009	0.035	-10000	0	-0.34	4	4
GNAI3	0.01	0.035	-10000	0	-0.34	4	4
GNAI1	0.01	0.045	-10000	0	-0.41	4	4
LPA/LPA3	0.017	0.044	0.17	10	-0.39	4	14
LPA/LPA2	0.017	0.011	-10000	0	-10000	0	0
LPA/LPA1	0.017	0.04	-10000	0	-0.39	4	4
HB-EGF/EGFR	0.006	0.082	0.26	9	-0.35	19	28
HBEGF	-0.024	0.065	-10000	0	-0.39	14	14
mol:DAG	-0.028	0.063	-10000	0	-0.29	9	9
cAMP biosynthetic process	-0.004	0.067	0.33	2	-0.41	4	6
NFKB1	0.022	0.005	-10000	0	-10000	0	0
SRC	0.022	0.004	-10000	0	-10000	0	0
GNB1	0.02	0.026	-10000	0	-0.54	1	1
LYN	-0.019	0.074	0.25	1	-0.34	10	11
GNAQ	0.009	0.033	0.19	1	-0.29	5	6
LPAR2	0.022	0.004	-10000	0	-10000	0	0
LPAR3	0.022	0.059	0.24	10	-0.53	4	14
LPAR1	0.022	0.036	-10000	0	-0.69	1	1
IL8	-0.016	0.12	0.3	3	-0.41	16	19
PTK2	0.004	0.048	-10000	0	-0.33	5	5
Rac1/GDP	0.016	0.003	-10000	0	-10000	0	0
CASP3	0.009	0.041	0.19	1	-0.29	8	9
EGFR	0.023	0.081	0.36	12	-0.53	6	18
PLCG1	-0.02	0.065	-10000	0	-0.24	15	15
PLD2	0.006	0.051	0.36	1	-0.33	5	6
G12/G13	0.041	0.036	-10000	0	-0.31	4	4
PI3K-beta	-0.008	0.073	-10000	0	-0.37	7	7
cell migration	0.013	0.058	0.17	1	-0.25	17	18
SLC9A3R2	0.02	0.035	-10000	0	-0.53	2	2
PXN	-0.001	0.066	0.35	1	-0.38	6	7
HRAS/GTP	0.004	0.061	-10000	0	-0.42	6	6
RAC1	0.022	0.004	-10000	0	-10000	0	0
MMP9	0.034	0.049	0.24	27	-10000	0	27
PRKCE	0.02	0.025	-10000	0	-0.53	1	1
PRKCD	-0.027	0.061	-10000	0	-0.3	4	4
Gi(beta/gamma)	0.008	0.065	-10000	0	-0.54	4	4
mol:LPA	0.001	0.014	-10000	0	-0.17	3	3
TRIP6/p130 Cas/FAK1/Paxillin	0.021	0.056	0.26	1	-0.38	2	3
MAPKKK cascade	0.004	0.06	-10000	0	-0.41	6	6
contractile ring contraction involved in cytokinesis	-0.021	0.095	-10000	0	-0.32	38	38
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.06	0.13	-10000	0	-0.3	116	116
GNA15	0.01	0.03	0.19	1	-0.29	4	5
GNA12	0.022	0.004	-10000	0	-10000	0	0
GNA13	0.022	0.003	-10000	0	-10000	0	0
MAPT	-0.002	0.096	0.29	5	-0.3	15	20
GNA11	0.01	0.03	0.19	1	-0.29	4	5
Rac1/GTP	0.007	0.17	-10000	0	-0.86	18	18
MMP2	0.007	0.063	-10000	0	-0.69	4	4

×

ErbB2/ErbB3 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	-0.007	0.006	-10000	0	-10000	0	0
RAS family/GTP	0.028	0.061	-10000	0	-0.3	2	2
NFATC4	-0.012	0.059	0.24	4	-0.24	3	7
ERBB2IP	0.021	0.007	-10000	0	-10000	0	0
HSP90 (dimer)	0.022	0.005	-10000	0	-10000	0	0
mammary gland morphogenesis	0.008	0.059	-10000	0	-0.29	13	13
JUN	0.013	0.061	0.2	4	-0.44	1	5
HRAS	0.022	0.004	-10000	0	-10000	0	0
DOCK7	-0.016	0.063	0.28	1	-0.28	13	14
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.025	0.057	-10000	0	-0.3	12	12
AKT1	-0.004	0.006	-10000	0	-10000	0	0
BAD	-0.008	0.004	-10000	0	-10000	0	0
MAPK10	-0.01	0.054	0.18	6	-0.24	7	13
mol:GTP	0	0.001	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	0.009	0.064	-10000	0	-0.31	13	13
RAF1	0.019	0.075	0.26	12	-0.35	1	13
ErbB2/ErbB3/neuregulin 2	-0.007	0.099	0.2	2	-0.32	44	46
STAT3	0.012	0.1	-10000	0	-0.79	8	8
cell migration	-0.005	0.054	0.22	8	-0.26	2	10
mol:PI-3-4-5-P3	0	0.001	-10000	0	-10000	0	0
cell proliferation	-0.016	0.17	0.43	1	-0.54	18	19
FOS	-0.033	0.19	0.31	3	-0.47	68	71
NRAS	0.021	0.005	-10000	0	-10000	0	0
mol:Ca2+	0.008	0.059	-10000	0	-0.29	13	13
MAPK3	-0.006	0.14	0.37	2	-0.53	15	17
MAPK1	-0.008	0.15	0.36	2	-0.55	18	20
JAK2	-0.017	0.059	-10000	0	-0.28	13	13
NF2	-0.002	0.071	-10000	0	-0.56	8	8
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0.01	0.053	0.19	1	-0.28	11	12
NRG1	0.005	0.092	-10000	0	-0.54	14	14
GRB2/SOS1	0.032	0.008	-10000	0	-10000	0	0
MAPK8	0.002	0.067	0.24	1	-0.29	13	14
MAPK9	-0.009	0.044	0.18	4	-10000	0	4
ERBB2	-0.016	0.021	0.29	2	-10000	0	2
ERBB3	0.023	0.003	-10000	0	-10000	0	0
SHC1	0.022	0.005	-10000	0	-10000	0	0
RAC1	0.022	0.004	-10000	0	-10000	0	0
apoptosis	0.005	0.017	-10000	0	-0.17	3	3
STAT3 (dimer)	0.014	0.1	-10000	0	-0.77	8	8
RNF41	-0.01	0.007	-10000	0	-10000	0	0
FRAP1	-0.003	0.003	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.024	0.034	-10000	0	-0.21	13	13
ErbB2/ErbB2/HSP90 (dimer)	-0.014	0.018	0.21	2	-10000	0	2
CHRNA1	0.003	0.13	0.34	2	-0.52	10	12
myelination	-0.001	0.077	0.29	13	-10000	0	13
PPP3CB	-0.015	0.059	0.27	1	-0.26	13	14
KRAS	0.021	0.006	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0.032	0.059	-10000	0	-0.25	11	11
NRG2	-0.036	0.16	-10000	0	-0.53	48	48
mol:GDP	0.01	0.053	0.18	2	-0.28	11	13
SOS1	0.022	0.004	-10000	0	-10000	0	0
MAP2K2	0.012	0.077	0.26	11	-0.39	1	12
SRC	0.022	0.004	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.001	-10000	0	-10000	0	0
PTPN11	-0.014	0.064	0.28	1	-0.28	13	14
MAP2K1	-0.011	0.15	0.4	1	-0.5	15	16
heart morphogenesis	0.008	0.059	-10000	0	-0.29	13	13
RAS family/GDP	0.033	0.062	-10000	0	-0.29	2	2
GRB2	0.022	0.004	-10000	0	-10000	0	0
PRKACA	0	0.079	-10000	0	-0.58	9	9
CHRNE	0.007	0.017	0.099	1	-0.2	1	2
HSP90AA1	0.022	0.005	-10000	0	-10000	0	0
activation of caspase activity	0.004	0.006	-10000	0	-10000	0	0
nervous system development	0.008	0.059	-10000	0	-0.29	13	13
CDC42	0.022	0.004	-10000	0	-10000	0	0

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.02	0.035	-10000	0	-0.53	2	2
ANTXR2	0.015	0.061	-10000	0	-0.53	6	6
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.002	0.009	-10000	0	-0.084	6	6
monocyte activation	-0.009	0.1	-10000	0	-0.37	34	34
MAP2K2	-0.009	0.11	-10000	0	-0.57	18	18
MAP2K1	-0.005	0.008	-10000	0	-0.1	1	1
MAP2K7	-0.005	0.008	-10000	0	-0.1	1	1
MAP2K6	-0.005	0.01	0.12	1	-10000	0	1
CYAA	-0.011	0.042	-10000	0	-0.37	6	6
MAP2K4	-0.005	0.007	-10000	0	-0.1	1	1
IL1B	-0.009	0.051	0.24	2	-0.28	14	16
Channel	0.022	0.049	-10000	0	-0.39	6	6
NLRP1	-0.006	0.025	-10000	0	-0.32	3	3
CALM1	0.022	0.005	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.003	0.068	-10000	0	-0.4	14	14
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.002	0.009	0.084	6	-10000	0	6
MAPK3	-0.005	0.009	-10000	0	-10000	0	0
MAPK1	-0.005	0.008	-10000	0	-10000	0	0
PGR	-0.06	0.11	-10000	0	-0.29	98	98
PA/Cellular Receptors	0.023	0.053	-10000	0	-0.43	6	6
apoptosis	-0.002	0.009	-10000	0	-0.084	6	6
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.021	0.046	-10000	0	-0.37	6	6
macrophage activation	-0.008	0.008	-10000	0	-10000	0	0
TNF	0.012	0.079	0.23	1	-0.53	10	11
VCAM1	-0.008	0.1	-10000	0	-0.37	32	32
platelet activation	-0.003	0.068	-10000	0	-0.4	14	14
MAPKKK cascade	0.001	0.021	0.12	2	-0.14	3	5
IL18	-0.005	0.032	-10000	0	-0.25	6	6
negative regulation of macrophage activation	-0.002	0.009	-10000	0	-0.084	6	6
LEF	-0.002	0.009	-10000	0	-0.085	6	6
CASP1	-0.003	0.023	-10000	0	-0.18	5	5
mol:cAMP	-0.004	0.069	-10000	0	-0.4	14	14
necrosis	-0.002	0.009	-10000	0	-0.084	6	6
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.021	0.047	-10000	0	-0.37	6	6
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.022	0.004	-10000	0	-10000	0	0
mol:PIP3	-0.005	0.017	-10000	0	-10000	0	0
FRAP1	0.049	0.058	0.26	2	-0.37	2	4
AKT1	0.052	0.079	0.19	17	-10000	0	17
INSR	0.022	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.025	0.007	-10000	0	-10000	0	0
mol:GTP	0.081	0.077	0.26	22	-10000	0	22
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0.006	0.015	-10000	0	-10000	0	0
TSC2	0.022	0.004	-10000	0	-10000	0	0
RHEB/GDP	0.008	0.017	-10000	0	-10000	0	0
TSC1	0.023	0.004	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.019	0.032	-10000	0	-0.18	10	10
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.015	0.026	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.022	0.004	-10000	0	-10000	0	0
RPS6KB1	0.075	0.08	0.23	42	-0.29	2	44
MAP3K5	0	0.025	0.19	2	-0.18	7	9
PIK3R1	0.021	0.007	-10000	0	-10000	0	0
apoptosis	0	0.025	0.19	2	-0.18	7	9
mol:LY294002	0	0	-10000	0	-0.001	12	12
EIF4B	0.07	0.077	0.23	42	-0.26	2	44
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.073	0.067	0.23	21	-0.25	1	22
eIF4E/eIF4G1/eIF4A1	0.008	0.017	-10000	0	-0.27	1	1
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.016	0.027	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.058	0.069	0.2	48	-0.15	1	49
FKBP1A	0.023	0.005	-10000	0	-10000	0	0
RHEB/GTP	0.062	0.058	-10000	0	-10000	0	0
mol:Amino Acids	0	0	-10000	0	-0.001	12	12
FKBP12/Rapamycin	0.019	0.006	-10000	0	-10000	0	0
PDPK1	-0.002	0.034	0.17	15	-10000	0	15
EIF4E	0.022	0.005	-10000	0	-10000	0	0
ASK1/PP5C	0.052	0.083	-10000	0	-0.52	8	8
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	-0.007	0.063	-10000	0	-0.34	6	6
TSC1/TSC2	0.092	0.085	0.29	26	-10000	0	26
tumor necrosis factor receptor activity	0	0	0.001	12	-10000	0	12
RPS6	0.021	0.007	-10000	0	-10000	0	0
PPP5C	0.022	0.004	-10000	0	-10000	0	0
EIF4G1	0.013	0.011	-10000	0	-10000	0	0
IRS1	0.005	0.031	-10000	0	-0.19	12	12
INS	-0.017	0.003	-10000	0	-10000	0	0
PTEN	0.019	0.007	-10000	0	-10000	0	0
PDK2	-0.002	0.031	0.16	13	-10000	0	13
EIF4EBP1	0.01	0.17	-10000	0	-1	11	11
PIK3CA	0.013	0.011	-10000	0	-10000	0	0
PPP2R5D	0.049	0.06	0.24	10	-0.34	2	12
peptide biosynthetic process	-0.013	0.015	0.17	3	-10000	0	3
RHEB	0.022	0.004	-10000	0	-10000	0	0
EIF4A1	0.021	0.005	-10000	0	-10000	0	0
mol:Rapamycin	0.001	0.002	0.004	69	-10000	0	69
EEF2	-0.013	0.015	0.18	3	-10000	0	3
eIF4E/4E-BP1	0.015	0.15	-10000	0	-0.93	11	11

×

Retinoic acid receptors-mediated 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
HDAC1	0.022	0.004	-10000	0	-10000	0	0
HDAC3	0.021	0.006	-10000	0	-10000	0	0
VDR	0.021	0.025	-10000	0	-0.53	1	1
Cbp/p300/PCAF	0.041	0.017	-10000	0	-10000	0	0
EP300	0.022	0.004	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.018	0.049	0.23	1	-0.37	6	7
KAT2B	0.021	0.006	-10000	0	-10000	0	0
MAPK14	0.022	0.004	-10000	0	-10000	0	0
AKT1	-0.009	0.055	-10000	0	-0.28	3	3
RAR alpha/9cRA/Cyclin H	0.037	0.044	-10000	0	-0.35	1	1
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	-0.001	0.086	-10000	0	-0.38	18	18
CDC2	0	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.021	0.029	-10000	0	-0.22	3	3
NCOR2	0.021	0.025	-10000	0	-0.53	1	1
VDR/VDR/Vit D3	0.016	0.018	-10000	0	-0.39	1	1
RXRs/RARs/NRIP1/9cRA	-0.033	0.11	-10000	0	-0.59	9	9
NCOA2	0.021	0.025	-10000	0	-0.53	1	1
NCOA3	0.022	0.004	-10000	0	-10000	0	0
NCOA1	0.022	0.003	-10000	0	-10000	0	0
VDR/VDR/DNA	0.021	0.025	-10000	0	-0.53	1	1
RARG	0.023	0.002	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.03	0.007	-10000	0	-10000	0	0
MAPK3	0.023	0.003	-10000	0	-10000	0	0
MAPK1	0.021	0.006	-10000	0	-10000	0	0
MAPK8	0.022	0.005	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.026	0.09	-10000	0	-0.51	6	6
RARA	0.015	0.023	0.2	1	-0.22	3	4
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.001	0.087	-10000	0	-0.35	23	23
PRKCA	0.022	0.035	-10000	0	-0.53	2	2
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.044	0.12	0.34	1	-0.58	12	13
RXRG	-0.15	0.18	-10000	0	-0.33	240	240
RXRA	0.012	0.029	-10000	0	-0.32	2	2
RXRB	0.018	0.032	0.25	1	-0.28	4	5
VDR/Vit D3/DNA	0.016	0.018	-10000	0	-0.39	1	1
RBP1	0.028	0.049	0.27	18	-10000	0	18
CRBP1/9-cic-RA	0.02	0.033	0.18	18	-10000	0	18
RARB	0.02	0.036	-10000	0	-0.53	2	2
PRKCG	0.036	0.058	0.24	34	-0.3	2	36
MNAT1	0.022	0.005	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.039	0.096	-10000	0	-0.54	9	9
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.023	0.091	0.24	1	-0.48	10	11
proteasomal ubiquitin-dependent protein catabolic process	-0.001	0.1	0.29	1	-0.38	25	26
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.045	0.12	0.34	1	-0.6	12	13
positive regulation of DNA binding	0.029	0.04	-10000	0	-0.33	1	1
NRIP1	-0.043	0.12	-10000	0	-0.67	6	6
RXRs/RARs	-0.048	0.13	-10000	0	-0.58	16	16
RXRs/RXRs/DNA/9cRA	-0.035	0.083	-10000	0	-0.49	7	7
PRKACA	0.022	0.004	-10000	0	-10000	0	0
CDK7	0.021	0.006	-10000	0	-10000	0	0
TFIIH	0.042	0.014	-10000	0	-10000	0	0
RAR alpha/9cRA	0.045	0.035	-10000	0	-10000	0	0
CCNH	0.021	0.006	-10000	0	-10000	0	0
CREBBP	0.022	0.005	-10000	0	-10000	0	0
RAR gamma2/9cRA	0.039	0.016	-10000	0	-10000	0	0

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.041	0.071	-10000	0	-0.67	1	1
UGCG	0.016	0.082	-10000	0	-0.69	6	6
AKT1/mTOR/p70S6K/Hsp90/TERT	0.073	0.11	0.29	13	-0.43	11	24
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.017	0.081	-10000	0	-0.68	6	6
mol:DAG	-0.019	0.16	-10000	0	-0.8	19	19
CaM/Ca2+/Calcineurin A alpha-beta B1	0.048	0.093	-10000	0	-0.4	8	8
FRAP1	0.047	0.1	0.49	1	-0.44	9	10
FOXO3	0.043	0.1	0.34	3	-0.43	10	13
AKT1	0.045	0.11	-10000	0	-0.45	11	11
GAB2	0.007	0.092	-10000	0	-0.53	14	14
SMPD1	0.005	0.12	-10000	0	-0.69	14	14
SGMS1	0.001	0.13	-10000	0	-0.64	18	18
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	-0.003	0.003	-10000	0	-10000	0	0
CALM1	0.022	0.005	-10000	0	-10000	0	0
cell proliferation	0.032	0.1	0.48	1	-0.44	16	17
EIF3A	0.022	0.004	-10000	0	-10000	0	0
PI3K	0.019	0.018	-10000	0	-10000	0	0
RPS6KB1	0.023	0.056	-10000	0	-0.79	2	2
mol:sphingomyelin	-0.019	0.16	-10000	0	-0.8	19	19
natural killer cell activation	0	0	-10000	0	-10000	0	0
JAK3	0.023	0.005	-10000	0	-10000	0	0
PIK3R1	0.022	0.007	-10000	0	-10000	0	0
JAK1	0.023	0.005	-10000	0	-10000	0	0
NFKB1	0.022	0.005	-10000	0	-10000	0	0
MYC	0.059	0.11	0.37	8	-0.45	5	13
MYB	0.017	0.083	-10000	0	-1.2	2	2
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.04	0.089	-10000	0	-0.47	7	7
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.044	0.055	-10000	0	-0.72	2	2
mol:PI-3-4-5-P3	0.042	0.089	-10000	0	-0.46	7	7
Rac1/GDP	0.01	0.01	-10000	0	-10000	0	0
T cell proliferation	0.041	0.085	0.26	2	-0.44	6	8
SHC1	0.022	0.005	-10000	0	-10000	0	0
RAC1	0.022	0.004	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.003	0.005	-10000	0	-0.064	2	2
PRKCZ	0.041	0.086	-10000	0	-0.46	6	6
NF kappa B1 p50/RelA	0.061	0.099	0.46	1	-0.44	5	6
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.008	0.053	-10000	0	-0.45	5	5
HSP90AA1	0.022	0.005	-10000	0	-10000	0	0
RELA	0.023	0.002	-10000	0	-10000	0	0
IL2RA	0.021	0.039	0.23	3	-0.53	2	5
IL2RB	0.02	0.043	-10000	0	-0.53	3	3
TERT	0.12	0.13	0.27	194	-0.3	1	195
E2F1	0.023	0.038	-10000	0	-0.41	3	3
SOS1	0.023	0.004	-10000	0	-10000	0	0
RPS6	0.021	0.007	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.003	0.03	2	-0.01	14	16
PTPN11	0.023	0.002	-10000	0	-10000	0	0
IL2RG	0.016	0.066	-10000	0	-0.53	7	7
actin cytoskeleton organization	0.041	0.085	0.26	2	-0.44	6	8
GRB2	0.023	0.004	-10000	0	-10000	0	0
IL2	0.02	0.006	-10000	0	-10000	0	0
PIK3CA	0.013	0.012	-10000	0	-10000	0	0
Rac1/GTP	0.023	0.023	-10000	0	-10000	0	0
LCK	0.023	0.025	-10000	0	-0.53	1	1
BCL2	0.045	0.093	0.48	2	-0.48	2	4

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	0.028	0.03	-10000	0	-0.33	2	2
cell-cell adhesion	0.019	0.021	0.26	2	-10000	0	2
Ephrin B/EPHB2/RasGAP	0.059	0.034	-10000	0	-0.29	1	1
ITSN1	0.022	0.004	-10000	0	-10000	0	0
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
SHC1	0.022	0.005	-10000	0	-10000	0	0
Ephrin B1/EPHB3	0.025	0.041	0.24	14	-10000	0	14
Ephrin B1/EPHB1	0.044	0.055	0.24	18	-0.33	1	19
HRAS/GDP	-0.024	0.09	-10000	0	-0.29	3	3
Ephrin B/EPHB1/GRB7	0.065	0.057	-10000	0	-0.29	1	1
Endophilin/SYNJ1	-0.011	0.026	0.2	1	-0.28	1	2
KRAS	0.021	0.006	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	0.064	0.056	-10000	0	-0.29	1	1
endothelial cell migration	0.023	0.028	-10000	0	-0.29	1	1
GRB2	0.022	0.004	-10000	0	-10000	0	0
GRB7	0.025	0.032	0.38	4	-10000	0	4
PAK1	0.004	0.072	0.31	3	-0.28	5	8
HRAS	0.022	0.004	-10000	0	-10000	0	0
RRAS	-0.012	0.025	-10000	0	-0.28	1	1
DNM1	0.023	0.014	0.23	2	-10000	0	2
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	0.007	0.068	0.34	1	-0.28	2	3
lamellipodium assembly	-0.019	0.021	-10000	0	-0.26	2	2
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.021	0.042	0.26	1	-0.26	2	3
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
EPHB2	0.025	0.027	0.23	8	-10000	0	8
EPHB3	0.025	0.064	0.34	18	-10000	0	18
EPHB1	0.05	0.09	0.27	61	-0.53	1	62
EPHB4	0.021	0.005	-10000	0	-10000	0	0
mol:GDP	-0.04	0.07	-10000	0	-0.32	2	2
Ephrin B/EPHB2	0.049	0.029	-10000	0	-0.29	1	1
Ephrin B/EPHB3	0.034	0.046	0.24	12	-0.29	1	13
JNK cascade	0.032	0.13	0.35	62	-0.29	1	63
Ephrin B/EPHB1	0.054	0.054	0.24	12	-0.29	2	14
RAP1/GDP	-0.03	0.086	-10000	0	-0.3	3	3
EFNB2	0.02	0.025	-10000	0	-0.53	1	1
EFNB3	0.022	0.014	0.23	2	-10000	0	2
EFNB1	0.023	0.003	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	0.051	0.058	0.24	16	-0.31	2	18
RAP1B	0.022	0.005	-10000	0	-10000	0	0
RAP1A	0.022	0.005	-10000	0	-10000	0	0
CDC42/GTP	0.039	0.046	-10000	0	-0.3	1	1
Rap1/GTP	0.011	0.029	-10000	0	-0.26	1	1
axon guidance	0.028	0.03	-10000	0	-0.33	2	2
MAPK3	0.01	0.039	0.23	4	-10000	0	4
MAPK1	0.01	0.043	0.25	6	-10000	0	6
Rac1/GDP	-0.038	0.084	-10000	0	-0.29	6	6
actin cytoskeleton reorganization	-0.039	0.044	-10000	0	-0.24	1	1
CDC42/GDP	-0.038	0.084	-10000	0	-0.29	6	6
PI3K	0.025	0.03	-10000	0	-0.29	1	1
EFNA5	0.019	0.036	-10000	0	-0.53	2	2
Ephrin B2/EPHB4	0.027	0.019	-10000	0	-0.33	1	1
Ephrin B/EPHB2/Intersectin/N-WASP	0.015	0.034	-10000	0	-0.25	1	1
CDC42	0.022	0.004	-10000	0	-10000	0	0
RAS family/GTP	-0.021	0.021	-10000	0	-0.26	1	1
PTK2	0.026	0.13	0.55	31	-10000	0	31
MAP4K4	0.033	0.13	0.35	62	-0.29	1	63
SRC	0.022	0.004	-10000	0	-10000	0	0
KALRN	0.015	0.056	-10000	0	-0.53	5	5
Intersectin/N-WASP	0.032	0.008	-10000	0	-10000	0	0
neuron projection morphogenesis	0.015	0.1	0.29	46	-0.38	1	47
MAP2K1	0.013	0.038	0.24	1	-10000	0	1
WASL	0.022	0.004	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	0.057	0.05	0.28	2	-0.31	1	3
cell migration	0.012	0.072	0.29	7	-10000	0	7
NRAS	0.022	0.005	-10000	0	-10000	0	0
SYNJ1	-0.011	0.026	0.2	1	-0.28	1	2
PXN	0.023	0.002	-10000	0	-10000	0	0
TF	-0.015	0.039	0.18	6	-0.28	5	11
HRAS/GTP	0.04	0.037	-10000	0	-0.26	2	2
Ephrin B1/EPHB1-2	0.054	0.056	0.24	18	-0.31	1	19
cell adhesion mediated by integrin	-0.02	0.051	0.29	1	-0.21	4	5
RAC1	0.022	0.004	-10000	0	-10000	0	0
mol:GTP	0.044	0.042	-10000	0	-0.28	2	2
RAC1-CDC42/GTP	-0.015	0.023	-10000	0	-0.26	2	2
RASA1	0.021	0.006	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.031	0.087	-10000	0	-0.29	4	4
ruffle organization	0.009	0.082	0.35	9	-10000	0	9
NCK1	0.019	0.008	-10000	0	-10000	0	0
receptor internalization	-0.014	0.026	0.2	1	-0.27	1	2
Ephrin B/EPHB2/KALRN	0.051	0.051	-10000	0	-0.29	6	6
ROCK1	0.07	0.094	0.18	209	-10000	0	209
RAS family/GDP	-0.043	0.047	-10000	0	-0.26	1	1
Rac1/GTP	-0.02	0.023	-10000	0	-0.27	2	2
Ephrin B/EPHB1/Src/Paxillin	0.019	0.042	-10000	0	-0.25	1	1

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.024	0.007	-10000	0	-10000	0	0
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.012	0.093	0.42	8	-10000	0	8
IL27/IL27R/JAK1	0.028	0.085	-10000	0	-10000	0	0
TBX21	-0.046	0.15	-10000	0	-0.48	38	38
IL12B	0.019	0.012	-10000	0	-10000	0	0
IL12A	-0.002	0.043	-10000	0	-0.39	6	6
IL6ST	0.001	0.099	-10000	0	-0.54	16	16
IL27RA/JAK1	0.015	0.033	-10000	0	-10000	0	0
IL27	0.017	0.015	-10000	0	-10000	0	0
TYK2	0.022	0.008	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.026	0.13	-10000	0	-0.77	1	1
T-helper 2 cell differentiation	0.012	0.093	0.42	8	-10000	0	8
T cell proliferation during immune response	0.012	0.093	0.42	8	-10000	0	8
MAPKKK cascade	-0.012	0.093	-10000	0	-0.42	8	8
STAT3	0.022	0.003	-10000	0	-10000	0	0
STAT2	0.023	0.002	-10000	0	-10000	0	0
STAT1	0.02	0.011	-10000	0	-10000	0	0
IL12RB1	-0.01	0.13	-10000	0	-0.53	29	29
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.024	0.098	-10000	0	-0.46	3	3
IL27/IL27R/JAK2/TYK2	-0.012	0.094	-10000	0	-0.42	8	8
positive regulation of T cell mediated cytotoxicity	-0.012	0.093	-10000	0	-0.42	8	8
STAT1 (dimer)	0.014	0.13	0.5	4	-0.6	3	7
JAK2	0.02	0.009	-10000	0	-10000	0	0
JAK1	0.02	0.011	-10000	0	-10000	0	0
STAT2 (dimer)	-0.004	0.1	-10000	0	-0.41	9	9
T cell proliferation	-0.056	0.14	-10000	0	-0.49	20	20
IL12/IL12R/TYK2/JAK2	-0.053	0.24	-10000	0	-0.81	39	39
IL17A	-0.026	0.13	-10000	0	-0.77	1	1
mast cell activation	0.012	0.093	0.42	8	-10000	0	8
IFNG	0.002	0.028	-10000	0	-0.1	18	18
T cell differentiation	-0.002	0.005	-10000	0	-0.019	14	14
STAT3 (dimer)	-0.005	0.1	-10000	0	-0.4	10	10
STAT5A (dimer)	-0.005	0.1	-10000	0	-0.4	9	9
STAT4 (dimer)	-0.008	0.11	-10000	0	-0.45	8	8
STAT4	0.013	0.07	-10000	0	-0.53	8	8
T cell activation	-0.005	0.003	-10000	0	-10000	0	0
IL27R/JAK2/TYK2	0.022	0.068	-10000	0	-10000	0	0
GATA3	-0.04	0.22	0.57	2	-1.3	14	16
IL18	-0.007	0.03	-10000	0	-0.39	3	3
positive regulation of mast cell cytokine production	-0.005	0.099	-10000	0	-0.39	10	10
IL27/EBI3	0.029	0.023	-10000	0	-10000	0	0
IL27RA	0.004	0.025	-10000	0	-10000	0	0
IL6	-0.062	0.2	-10000	0	-0.53	77	77
STAT5A	0.022	0.003	-10000	0	-10000	0	0
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	-0.012	0.018	-10000	0	-10000	0	0
IL1B	-0.014	0.056	-10000	0	-0.39	11	11
EBI3	0.02	0.029	0.23	1	-0.53	1	2
TNF	-0.013	0.054	-10000	0	-0.39	10	10

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.007	0.092	-10000	0	-0.53	14	14
ELF1	0.024	0.019	-10000	0	-0.35	1	1
CCNA2	0.074	0.095	0.23	127	-0.3	2	129
PIK3CA	0.013	0.012	-10000	0	-10000	0	0
JAK3	0.022	0.005	-10000	0	-10000	0	0
PIK3R1	0.021	0.007	-10000	0	-10000	0	0
JAK1	0.022	0.005	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.037	0.093	-10000	0	-0.47	7	7
SHC1	0.022	0.005	-10000	0	-10000	0	0
SP1	0.023	0.034	-10000	0	-0.35	4	4
IL2RA	0.01	0.044	-10000	0	-0.65	2	2
IL2RB	0.019	0.043	-10000	0	-0.53	3	3
SOS1	0.023	0.004	-10000	0	-10000	0	0
IL2RG	0.015	0.065	-10000	0	-0.53	7	7
G1/S transition of mitotic cell cycle	0.032	0.1	0.37	3	-0.66	4	7
PTPN11	0.023	0.002	-10000	0	-10000	0	0
CCND2	0.005	0.072	-10000	0	-0.79	4	4
LCK	0.021	0.025	-10000	0	-0.53	1	1
GRB2	0.022	0.004	-10000	0	-10000	0	0
IL2	0.003	0.02	-10000	0	-10000	0	0
CDK6	0.023	0.023	0.38	2	-10000	0	2
CCND3	0.035	0.091	0.37	1	-0.57	2	3

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.004	0.09	0.25	1	-0.35	20	21
PDGFB-D/PDGFRB/SLAP	0.009	0.094	-10000	0	-0.4	24	24
PDGFB-D/PDGFRB/APS/CBL	0.04	0.023	-10000	0	-0.34	1	1
AKT1	0.064	0.1	0.29	29	-10000	0	29
mol:PI-4-5-P2	0	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.007	0.1	0.24	1	-0.38	23	24
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
FGR	-0.045	0.19	0.32	1	-0.58	48	49
mol:Ca2+	-0.003	0.11	-10000	0	-0.4	31	31
MYC	0.02	0.1	0.36	2	-0.36	7	9
SHC1	0.022	0.005	-10000	0	-10000	0	0
HRAS/GDP	0.026	0.035	-10000	0	-0.29	1	1
LRP1/PDGFRB/PDGFB	0.042	0.022	-10000	0	-0.34	1	1
GRB10	0.022	0.005	-10000	0	-10000	0	0
PTPN11	0.023	0.002	-10000	0	-10000	0	0
GO:0007205	-0.004	0.12	-10000	0	-0.4	31	31
PTEN	0.02	0.007	-10000	0	-10000	0	0
GRB2	0.022	0.004	-10000	0	-10000	0	0
GRB7	0.025	0.032	0.38	4	-10000	0	4
PDGFB-D/PDGFRB/SHP2	0.031	0.021	-10000	0	-0.39	1	1
PDGFB-D/PDGFRB/GRB10	0.03	0.022	-10000	0	-0.39	1	1
cell cycle arrest	0.009	0.094	-10000	0	-0.4	24	24
HRAS	0.022	0.004	-10000	0	-10000	0	0
HIF1A	0.056	0.096	0.28	30	-10000	0	30
GAB1	-0.001	0.11	0.24	1	-0.4	23	24
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	0	0.096	0.26	4	-0.36	17	21
PDGFB-D/PDGFRB	0.041	0.024	-10000	0	-0.35	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.031	0.021	-10000	0	-0.39	1	1
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.007	0.072	-10000	0	-0.36	6	6
positive regulation of MAPKKK cascade	0.031	0.021	-10000	0	-0.39	1	1
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
mol:IP3	-0.004	0.12	-10000	0	-0.4	31	31
E5	0	0.001	-10000	0	-10000	0	0
CSK	0.022	0.005	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7	0.032	0.03	0.27	4	-0.39	1	5
SHB	0.021	0.007	-10000	0	-10000	0	0
BLK	-0.045	0.17	-10000	0	-0.47	60	60
PTPN2	0.022	0.006	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.031	0.021	-10000	0	-0.39	1	1
BCAR1	0.022	0.005	-10000	0	-10000	0	0
VAV2	-0.001	0.12	-10000	0	-0.42	22	22
CBL	0.022	0.004	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.03	0.029	-10000	0	-0.4	2	2
LCK	-0.005	0.11	0.32	1	-0.54	15	16
PDGFRB	0.021	0.026	-10000	0	-0.54	1	1
ACP1	0.022	0.003	-10000	0	-10000	0	0
HCK	0.003	0.072	0.32	1	-0.49	6	7
ABL1	-0.002	0.1	0.22	2	-0.4	19	21
PDGFB-D/PDGFRB/CBL	-0.005	0.13	-10000	0	-0.44	30	30
PTPN1	0.022	0.005	-10000	0	-10000	0	0
SNX15	0.023	0.002	-10000	0	-10000	0	0
STAT3	0.022	0.003	-10000	0	-10000	0	0
STAT1	0.022	0.004	-10000	0	-10000	0	0
cell proliferation	0.021	0.097	0.3	5	-0.33	8	13
SLA	-0.006	0.12	-10000	0	-0.53	24	24
actin cytoskeleton reorganization	0.021	0.082	0.33	8	-0.29	1	9
SRC	0.006	0.068	0.31	1	-0.64	3	4
PI3K	-0.011	0.017	-10000	0	-0.27	1	1
PDGFB-D/PDGFRB/GRB7/SHC	0.042	0.026	0.25	4	-10000	0	4
SH2B2	0.022	0.005	-10000	0	-10000	0	0
PLCgamma1/SPHK1	0.007	0.11	0.24	1	-0.39	23	24
LYN	0.001	0.082	0.3	1	-0.53	8	9
LRP1	0.023	0.002	-10000	0	-10000	0	0
SOS1	0.022	0.004	-10000	0	-10000	0	0
STAT5B	0.022	0.003	-10000	0	-10000	0	0
STAT5A	0.022	0.003	-10000	0	-10000	0	0
NCK1-2/p130 Cas	0.05	0.036	-10000	0	-0.29	1	1
SPHK1	0.022	0.005	-10000	0	-10000	0	0
EDG1	0	0.002	-10000	0	-10000	0	0
mol:DAG	-0.004	0.12	-10000	0	-0.4	31	31
PLCG1	-0.004	0.12	-10000	0	-0.42	30	30
NHERF/PDGFRB	0.041	0.036	0.25	1	-0.33	3	4
YES1	0.001	0.076	-10000	0	-0.54	7	7
cell migration	0.041	0.035	0.25	1	-0.33	3	4
SHC/Grb2/SOS1	0.057	0.03	-10000	0	-10000	0	0
SLC9A3R2	0.02	0.035	-10000	0	-0.53	2	2
SLC9A3R1	0.024	0.023	0.27	4	-10000	0	4
NHERF1-2/PDGFRB/PTEN	0.047	0.038	-10000	0	-0.3	3	3
FYN	0.004	0.067	-10000	0	-0.52	5	5
DOK1	-0.003	0.041	-10000	0	-0.32	1	1
HRAS/GTP	0.016	0.003	-10000	0	-10000	0	0
PDGFB	0.022	0.004	-10000	0	-10000	0	0
RAC1	0.003	0.11	0.31	1	-0.41	17	18
PRKCD	-0.002	0.043	0.18	17	-0.32	1	18
FER	-0.002	0.043	0.18	11	-0.32	1	12
MAPKKK cascade	0.006	0.074	0.4	7	-10000	0	7
RASA1	-0.002	0.043	0.18	11	-0.32	1	12
NCK1	0.019	0.008	-10000	0	-10000	0	0
NCK2	0.023	0.002	-10000	0	-10000	0	0
p62DOK/Csk	0.027	0.034	-10000	0	-0.29	1	1
PDGFB-D/PDGFRB/SHB	0.029	0.022	-10000	0	-0.39	1	1
chemotaxis	-0.002	0.1	0.22	6	-0.39	19	25
STAT1-3-5/STAT1-3-5	0.047	0.027	-10000	0	-0.28	1	1
Bovine Papilomavirus E5/PDGFRB	0.015	0.019	-10000	0	-0.39	1	1
PTPRJ	0.021	0.025	-10000	0	-0.53	1	1

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.097	0.2	-10000	0	-0.78	3	3
PCK1	-0.048	0.14	0.44	1	-0.63	3	4
HNF4A	-0.14	0.3	0.59	1	-0.84	56	57
KCNJ11	-0.097	0.23	-10000	0	-0.96	12	12
AKT1	0.045	0.073	-10000	0	-10000	0	0
response to starvation	-0.01	0.034	-10000	0	-0.19	3	3
DLK1	-0.082	0.2	-10000	0	-0.78	2	2
NKX2-1	-0.033	0.14	0.32	22	-0.44	3	25
ACADM	-0.098	0.2	-10000	0	-0.78	3	3
TAT	-0.049	0.15	-10000	0	-0.74	5	5
CEBPB	0.023	0.005	-10000	0	-10000	0	0
CEBPA	0.021	0.026	-10000	0	-0.53	1	1
TTR	-0.027	0.17	0.6	2	-0.82	5	7
PKLR	-0.093	0.2	-10000	0	-0.78	3	3
APOA1	-0.23	0.46	0.55	1	-1.3	63	64
CPT1C	-0.1	0.2	-10000	0	-0.78	3	3
ALAS1	-0.045	0.13	-10000	0	-10000	0	0
TFRC	-0.022	0.14	-10000	0	-0.6	2	2
FOXF1	-0.036	0.17	-10000	0	-0.53	52	52
NF1	0.025	0.005	-10000	0	-10000	0	0
HNF1A (dimer)	0.034	0.029	0.25	8	-10000	0	8
CPT1A	-0.092	0.2	-10000	0	-0.78	3	3
HMGCS1	-0.075	0.2	0.57	1	-0.76	2	3
NR3C1	0.026	0.008	-10000	0	-10000	0	0
CPT1B	-0.098	0.2	-10000	0	-0.78	3	3
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.029	0.01	-10000	0	-10000	0	0
GCK	-0.095	0.2	0.52	1	-0.78	3	4
CREB1	0.026	0.007	-10000	0	-10000	0	0
IGFBP1	-0.047	0.13	-10000	0	-0.63	2	2
PDX1	-0.035	0.13	-10000	0	-10000	0	0
UCP2	-0.096	0.2	-10000	0	-0.78	3	3
ALDOB	-0.087	0.19	-10000	0	-0.78	2	2
AFP	0.011	0.065	-10000	0	-10000	0	0
BDH1	-0.043	0.2	0.51	2	-0.72	3	5
HADH	-0.085	0.19	-10000	0	-0.78	2	2
F2	-0.14	0.28	-10000	0	-0.83	29	29
HNF1A	0.034	0.029	0.25	8	-10000	0	8
G6PC	0.022	0.057	-10000	0	-10000	0	0
SLC2A2	-0.021	0.12	-10000	0	-0.63	1	1
INS	-0.023	0.006	-10000	0	-10000	0	0
FOXA1	0.021	0.081	-10000	0	-0.53	10	10
FOXA3	0.032	0.094	0.35	4	-0.52	12	16
FOXA2	-0.097	0.23	-10000	0	-0.88	2	2
ABCC8	-0.095	0.22	-10000	0	-0.94	9	9
ALB	0.011	0.063	-10000	0	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	0.03	0.007	-10000	0	-10000	0	0
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0.022	0.004	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.023	0.01	0.23	1	-10000	0	1
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.022	0.005	-10000	0	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.007	0.011	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.021	0.006	-10000	0	-10000	0	0
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	0.022	0.003	-10000	0	-10000	0	0
FYN	0.021	0.025	-10000	0	-0.53	1	1
MAP3K12	0.023	0.002	-10000	0	-10000	0	0
FGR	-0.014	0.14	-10000	0	-0.53	32	32
p38 alpha/TAB1	-0.028	0.083	-10000	0	-0.36	22	22
PRKG1	-0.028	0.16	-10000	0	-0.53	45	45
DUSP8	0.014	0.065	-10000	0	-0.53	7	7
PGK/cGMP/p38 alpha	-0.011	0.12	-10000	0	-0.39	28	28
apoptosis	-0.027	0.08	-10000	0	-0.35	22	22
RAL/GTP	0.029	0.007	-10000	0	-10000	0	0
LYN	0.02	0.035	-10000	0	-0.53	2	2
DUSP1	-0.035	0.17	-10000	0	-0.53	50	50
PAK1	0.023	0.016	0.38	1	-10000	0	1
SRC	0.022	0.004	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.052	0.019	-10000	0	-10000	0	0
TRAF6	0.022	0.004	-10000	0	-10000	0	0
RAC1	0.022	0.004	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
mol:cGMP	0	0	-10000	0	-10000	0	0
CCM2	0.022	0.005	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0.029	0.008	-10000	0	-10000	0	0
MAPK11	0.013	0.099	0.26	3	-0.36	16	19
BLK	0.013	0.088	0.23	12	-0.53	11	23
HCK	0.018	0.043	-10000	0	-0.53	3	3
MAP2K3	0.022	0.005	-10000	0	-10000	0	0
DUSP16	0.021	0.005	-10000	0	-10000	0	0
DUSP10	0.021	0.025	-10000	0	-0.53	1	1
TRAF6/MEKK3	0.028	0.006	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.008	0.11	0.21	2	-0.41	20	22
positive regulation of innate immune response	0.012	0.12	0.26	3	-0.42	22	25
LCK	0.021	0.025	-10000	0	-0.53	1	1
p38alpha-beta/MKP7	0.018	0.12	0.25	1	-0.42	19	20
p38alpha-beta/MKP5	0.02	0.12	0.25	1	-0.43	19	20
PGK/cGMP	-0.021	0.12	-10000	0	-0.39	45	45
PAK2	0.014	0.011	-10000	0	-10000	0	0
p38alpha-beta/MKP1	-0.003	0.14	0.31	1	-0.42	28	29
CDC42	0.022	0.004	-10000	0	-10000	0	0
RALB	0.022	0.003	-10000	0	-10000	0	0
RALA	0.022	0.004	-10000	0	-10000	0	0
PAK3	0.015	0.039	0.23	1	-0.53	2	3

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.015	0.063	0.38	1	-0.53	6	7
HRAS	0.022	0.004	-10000	0	-10000	0	0
EGFR	0.023	0.081	0.36	12	-0.53	6	18
AKT	0.064	0.081	0.26	21	-0.33	2	23
FOXO3	0.023	0.002	-10000	0	-10000	0	0
AKT1	0.022	0.005	-10000	0	-10000	0	0
FOXO1	0.021	0.006	-10000	0	-10000	0	0
AKT3	0.019	0.043	-10000	0	-0.53	3	3
FOXO4	0.023	0.002	-10000	0	-10000	0	0
MET	0.02	0.039	0.38	1	-0.53	2	3
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
PIK3CB	0.019	0.009	-10000	0	-10000	0	0
NRAS	0.022	0.005	-10000	0	-10000	0	0
PIK3CG	-0.024	0.15	-10000	0	-0.53	41	41
PIK3R3	0.021	0.025	-10000	0	-0.53	1	1
PIK3R2	0.022	0.004	-10000	0	-10000	0	0
NF1	0.022	0.004	-10000	0	-10000	0	0
RAS	0.023	0.048	0.25	5	-0.22	4	9
ERBB2	0.023	0.023	0.38	2	-10000	0	2
proliferation/survival/translation	-0.063	0.07	0.27	3	-0.26	10	13
PI3K	0.047	0.074	0.23	34	-0.21	6	40
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
KRAS	0.021	0.006	-10000	0	-10000	0	0
FOXO	0.081	0.064	0.23	33	-10000	0	33
AKT2	0.021	0.007	-10000	0	-10000	0	0
PTEN	0.02	0.007	-10000	0	-10000	0	0

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	0.012	0.089	-10000	0	-0.28	38	38
TC10/GTP	0.01	0.083	-10000	0	-0.27	35	35
Insulin Receptor/Insulin/IRS1/Shp2	0.053	0.018	-10000	0	-10000	0	0
HRAS	0.022	0.004	-10000	0	-10000	0	0
APS homodimer	0.021	0.005	-10000	0	-10000	0	0
GRB14	-0.01	0.13	0.23	1	-0.53	29	30
FOXO3	0.031	0.053	-10000	0	-0.54	3	3
AKT1	0.044	0.11	0.31	7	-10000	0	7
INSR	0.024	0.007	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.043	0.024	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.022	0.005	-10000	0	-10000	0	0
SORBS1	-0.033	0.16	-10000	0	-0.53	49	49
CRK	0.021	0.005	-10000	0	-10000	0	0
PTPN1	0.002	0.036	-10000	0	-10000	0	0
CAV1	-0.082	0.12	-10000	0	-0.3	126	126
CBL/APS/CAP/Crk-II/C3G	0.027	0.099	-10000	0	-0.29	38	38
Insulin Receptor/Insulin/IRS1/NCK2	0.053	0.018	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.023	0.024	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.019	0.054	-10000	0	-0.36	3	3
RPS6KB1	0.038	0.1	0.3	6	-10000	0	6
PARD6A	0.021	0.025	-10000	0	-0.53	1	1
CBL	0.022	0.004	-10000	0	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.017	0.007	-10000	0	-10000	0	0
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	0.048	0.084	-10000	0	-10000	0	0
HRAS/GTP	-0.019	0.017	-10000	0	-0.26	1	1
Insulin Receptor	0.024	0.007	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.059	0.025	-10000	0	-10000	0	0
PRKCI	0.01	0.03	-10000	0	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	0.001	0.061	-10000	0	-0.27	20	20
SHC1	0.022	0.005	-10000	0	-10000	0	0
negative regulation of MAPKKK cascade	0.032	0.021	-10000	0	-10000	0	0
PI3K	0.028	0.029	-10000	0	-10000	0	0
NCK2	0.023	0.002	-10000	0	-10000	0	0
RHOQ	0.022	0.005	-10000	0	-10000	0	0
mol:H2O2	0	0.004	-10000	0	-10000	0	0
HRAS/GDP	0.016	0.003	-10000	0	-10000	0	0
AKT2	0.039	0.11	0.3	8	-10000	0	8
PRKCZ	0.006	0.043	-10000	0	-10000	0	0
SH2B2	0.022	0.005	-10000	0	-10000	0	0
SHC/SHIP	0.021	0.021	-10000	0	-0.29	1	1
F2RL2	0.048	0.095	0.23	80	-0.35	9	89
TRIP10	0.022	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insulin/Shc	0.039	0.015	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.028	0.009	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.058	0.025	-10000	0	-10000	0	0
RAPGEF1	0.022	0.003	-10000	0	-10000	0	0
RASA1	0.021	0.006	-10000	0	-10000	0	0
NCK1	0.019	0.008	-10000	0	-10000	0	0
CBL/APS/CAP/Crk-II	0.018	0.1	-10000	0	-0.31	39	39
TC10/GDP	0.016	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.05	0.021	-10000	0	-10000	0	0
INPP5D	-0.011	0.024	-10000	0	-0.3	1	1
SOS1	0.022	0.004	-10000	0	-10000	0	0
SGK1	0.002	0.055	-10000	0	-0.6	4	4
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.023	0.002	-10000	0	-10000	0	0
IRS1	0.022	0.004	-10000	0	-10000	0	0
p62DOK/RasGAP	0.033	0.021	-10000	0	-10000	0	0
INS	0.019	0.008	-10000	0	-10000	0	0
mol:PI-3-4-P2	-0.01	0.024	-10000	0	-0.3	1	1
GRB2	0.022	0.004	-10000	0	-10000	0	0
EIF4EBP1	0.039	0.11	0.31	16	-10000	0	16
PTPRA	0.023	0.006	-10000	0	-10000	0	0
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
TC10/GTP/CIP4	0.028	0.009	-10000	0	-10000	0	0
PDPK1	0.022	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.018	0.018	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.04	0.014	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS3	0.032	0.011	-10000	0	-10000	0	0
Par3/Par6	0.058	0.058	-10000	0	-0.31	2	2

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	0.029	0.035	0.23	1	-0.33	2	3
EFNA5	0.019	0.036	-10000	0	-0.53	2	2
FYN	-0.011	0.034	0.18	8	-0.3	3	11
neuron projection morphogenesis	0.029	0.035	0.23	1	-0.33	2	3
cell-cell signaling	0	0	-10000	0	-10000	0	0
Ephrin A5/EPHA5	0.029	0.035	0.24	1	-0.34	2	3
EPHA5	0.019	0.051	0.24	21	-10000	0	21

×

IFN-gamma pathway

Figure S90. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S90. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.042	0.044	-10000	0	-0.28	4	4
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	0.021	0.006	-10000	0	-10000	0	0
STAT1 (dimer)/Cbp/p300	0.037	0.044	0.27	1	-10000	0	1
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.04	0.022	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	0.002	0.032	-10000	0	-10000	0	0
CaM/Ca2+	0.041	0.044	-10000	0	-0.27	4	4
RAP1A	0.022	0.005	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	0.023	0.041	-10000	0	-0.27	3	3
AKT1	0.064	0.097	0.29	19	-10000	0	19
MAP2K1	-0.01	0.047	0.27	1	-0.31	1	2
MAP3K11	-0.007	0.046	0.27	1	-0.27	4	5
IFNGR1	0.023	0.008	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.005	0.12	-10000	0	-0.39	36	36
Rap1/GTP	-0.02	0.019	-10000	0	-10000	0	0
CRKL/C3G	0.031	0.01	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.053	0.043	-10000	0	-0.29	4	4
CEBPB	-0.017	0.15	-10000	0	-0.6	11	11
STAT3	0.022	0.003	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.037	0.13	-10000	0	-0.7	13	13
STAT1	-0.005	0.044	0.27	1	-0.27	3	4
CALM1	0.022	0.005	-10000	0	-10000	0	0
IFN-gamma (dimer)	0.017	0.053	0.25	2	-0.54	4	6
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
STAT1 (dimer)/PIAS1	0.023	0.045	0.27	1	-0.26	3	4
CEBPB/PTGES2/Cbp/p300	0.001	0.096	-10000	0	-0.39	8	8
mol:Ca2+	0.039	0.042	-10000	0	-0.28	4	4
MAPK3	-0.005	0.11	-10000	0	-0.68	8	8
STAT1 (dimer)	0.007	0.045	-10000	0	-10000	0	0
MAPK1	-0.006	0.1	-10000	0	-0.62	8	8
JAK2	0.021	0.01	-10000	0	-10000	0	0
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
JAK1	0.023	0.009	-10000	0	-10000	0	0
CAMK2D	0.022	0.005	-10000	0	-10000	0	0
DAPK1	-0.03	0.18	0.32	1	-0.61	38	39
SMAD7	0.031	0.047	0.16	20	-10000	0	20
CBL/CRKL/C3G	0.029	0.044	0.27	1	-10000	0	1
PI3K	0.023	0.038	-10000	0	-0.26	2	2
IFNG	0.017	0.053	0.25	2	-0.54	4	6
apoptosis	-0.013	0.13	-10000	0	-0.44	39	39
CAMK2G	0.022	0.004	-10000	0	-10000	0	0
STAT3 (dimer)	0.022	0.003	-10000	0	-10000	0	0
CAMK2A	-0.014	0.13	-10000	0	-0.53	31	31
CAMK2B	0.047	0.073	0.24	58	-0.3	1	59
FRAP1	0.059	0.091	0.28	19	-10000	0	19
PRKCD	0.063	0.098	0.3	19	-10000	0	19
RAP1B	0.022	0.005	-10000	0	-10000	0	0
negative regulation of cell growth	0.002	0.032	-10000	0	-10000	0	0
PTPN2	0.022	0.005	-10000	0	-10000	0	0
EP300	0.022	0.004	-10000	0	-10000	0	0
IRF1	0.002	0.047	0.26	2	-0.33	1	3
STAT1 (dimer)/PIASy	0.02	0.045	0.27	1	-0.28	1	2
SOCS1	-0.005	0.17	-10000	0	-1	13	13
mol:GDP	0.027	0.042	0.25	1	-0.24	3	4
CASP1	0.032	0.052	0.16	22	-0.25	2	24
PTGES2	0.022	0.003	-10000	0	-10000	0	0
IRF9	0.008	0.045	0.14	1	-0.19	1	2
mol:PI-3-4-5-P3	0.016	0.031	-10000	0	-0.25	2	2
RAP1/GDP	0.025	0.032	-10000	0	-10000	0	0
CBL	-0.006	0.046	0.27	1	-0.27	4	5
MAP3K1	-0.007	0.046	0.27	1	-0.27	4	5
PIAS1	0.023	0.002	-10000	0	-10000	0	0
PIAS4	0.022	0.004	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	0.002	0.032	-10000	0	-10000	0	0
PTPN11	-0.002	0.049	0.29	1	-0.28	4	5
CREBBP	0.022	0.005	-10000	0	-10000	0	0
RAPGEF1	0.022	0.003	-10000	0	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.021	0.006	-10000	0	-10000	0	0
NFATC1	0.027	0.079	0.49	2	-0.38	3	5
NFATC2	-0.02	0.095	0.19	2	-0.27	40	42
NFATC3	0.012	0.009	-10000	0	-10000	0	0
YWHAE	0.022	0.005	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.023	0.12	-10000	0	-0.42	31	31
Exportin 1/Ran/NUP214	0.041	0.014	-10000	0	-10000	0	0
mol:DAG	-0.001	0.002	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.002	0.12	-10000	0	-0.38	29	29
BCL2/BAX	0.033	0.013	0.27	1	-10000	0	1
CaM/Ca2+/Calcineurin A alpha-beta B1	0.012	0.014	-10000	0	-10000	0	0
CaM/Ca2+	0.012	0.014	-10000	0	-10000	0	0
BAX	0.022	0.004	-10000	0	-10000	0	0
MAPK14	0.022	0.004	-10000	0	-10000	0	0
BAD	0.023	0.002	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.012	0.12	-10000	0	-0.39	32	32
Calcineurin A alpha-beta B1/BCL2	0.023	0.016	0.38	1	-10000	0	1
FKBP8	0.022	0.004	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.011	0.12	0.39	32	-10000	0	32
KPNB1	0.022	0.003	-10000	0	-10000	0	0
KPNA2	0.022	0.004	-10000	0	-10000	0	0
XPO1	0.021	0.007	-10000	0	-10000	0	0
SFN	0.039	0.069	0.23	46	-0.38	3	49
MAP3K8	0.017	0.027	-10000	0	-0.53	1	1
NFAT4/CK1 alpha	0.017	0.021	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.018	0.14	-10000	0	-0.32	64	64
CABIN1	-0.022	0.12	-10000	0	-0.42	30	30
CALM1	0.017	0.014	-10000	0	-10000	0	0
RAN	0.023	0.002	-10000	0	-10000	0	0
MAP3K1	0.021	0.006	-10000	0	-10000	0	0
CAMK4	0.019	0.036	-10000	0	-0.53	2	2
mol:Ca2+	-0.001	0.005	-10000	0	-10000	0	0
MAPK3	0.022	0.003	-10000	0	-10000	0	0
YWHAH	0.022	0.004	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.03	0.028	-10000	0	-0.39	2	2
YWHAB	0.022	0.004	-10000	0	-10000	0	0
MAPK8	0.018	0.013	-10000	0	-10000	0	0
MAPK9	0.021	0.006	-10000	0	-10000	0	0
YWHAG	0.022	0.004	-10000	0	-10000	0	0
FKBP1A	0.022	0.005	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.015	0.093	0.28	1	-0.39	6	7
PRKCH	0.022	0.004	-10000	0	-10000	0	0
CABIN1/Cbp/p300	0.023	0.025	-10000	0	-10000	0	0
CASP3	0.02	0.007	-10000	0	-10000	0	0
PIM1	0.022	0.004	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.012	0.009	-10000	0	-10000	0	0
apoptosis	0.015	0.01	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.011	0.04	-10000	0	-0.26	5	5
PRKCB	-0.006	0.12	-10000	0	-0.53	25	25
PRKCE	0.02	0.025	-10000	0	-0.53	1	1
JNK2/NFAT4	0.024	0.026	-10000	0	-10000	0	0
BAD/BCL-XL	0.031	0.009	-10000	0	-10000	0	0
PRKCD	0.021	0.007	-10000	0	-10000	0	0
NUP214	0.022	0.003	-10000	0	-10000	0	0
PRKCZ	0.018	0.013	-10000	0	-10000	0	0
PRKCA	0.02	0.035	-10000	0	-0.53	2	2
PRKCG	0.028	0.062	0.23	34	-0.3	2	36
PRKCQ	-0.025	0.15	-10000	0	-0.53	42	42
FKBP38/BCL2	0.032	0.014	0.27	1	-10000	0	1
EP300	0.016	0.017	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.022	0.005	-10000	0	-10000	0	0
NFATc/JNK1	0.036	0.077	0.46	2	-0.36	3	5
CaM/Ca2+/FKBP38	0.023	0.019	-10000	0	-10000	0	0
FKBP12/FK506	0.016	0.003	-10000	0	-10000	0	0
CSNK1A1	0.005	0.013	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0.02	0.03	-10000	0	-0.34	2	2
NFATc/ERK1	0.039	0.078	0.46	2	-0.38	2	4
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	0	0.12	-10000	0	-0.38	30	30
NR4A1	-0.063	0.2	0.22	2	-0.52	73	75
GSK3B	0.017	0.012	-10000	0	-10000	0	0
positive T cell selection	0.012	0.009	-10000	0	-10000	0	0
NFAT1/CK1 alpha	-0.011	0.071	0.16	1	-0.3	13	14
RCH1/ KPNB1	0.033	0.006	-10000	0	-10000	0	0
YWHAQ	0.022	0.004	-10000	0	-10000	0	0
PRKACA	0.021	0.005	-10000	0	-10000	0	0
AKAP5	0.02	0.035	-10000	0	-0.53	2	2
MEF2D	0.016	0.017	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.022	0.005	-10000	0	-10000	0	0
NFATc/p38 alpha	0.038	0.078	0.46	2	-0.36	3	5
CREBBP	0.016	0.017	-10000	0	-10000	0	0
BCL2	0.023	0.016	0.38	1	-10000	0	1

×

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

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
BAG4	0.019	0.018	0.38	1	-10000	0	1
Caspase 8 (4 units)	0.028	0.068	-10000	0	-0.29	3	3
NEF	-0.005	0.037	-10000	0	-0.2	15	15
NFKBIA	0.022	0.014	-10000	0	-10000	0	0
BIRC3	0.012	0.066	-10000	0	-0.51	6	6
CYCS	0.009	0.063	0.26	1	-0.28	9	10
RIPK1	0.022	0.004	-10000	0	-10000	0	0
CD247	0.003	0.1	-10000	0	-0.38	25	25
MAP2K7	0.009	0.14	0.29	1	-0.62	17	18
protein ubiquitination	0.022	0.074	0.3	5	-0.35	3	8
CRADD	0.023	0.002	-10000	0	-10000	0	0
DAXX	0.022	0.004	-10000	0	-10000	0	0
FAS	0.02	0.025	-10000	0	-0.53	1	1
BID	0.012	0.066	-10000	0	-0.28	13	13
NF-kappa-B/RelA/I kappa B alpha	0.043	0.036	-10000	0	-0.28	5	5
TRADD	0.022	0.005	-10000	0	-10000	0	0
MAP3K5	0.022	0.003	-10000	0	-10000	0	0
CFLAR	0.022	0.004	-10000	0	-10000	0	0
FADD	0.019	0.008	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.043	0.036	-10000	0	-0.28	5	5
MAPK8	0.009	0.13	0.28	1	-0.57	17	18
APAF1	0.023	0.002	-10000	0	-10000	0	0
TRAF1	0.022	0.003	-10000	0	-10000	0	0
TRAF2	0.022	0.004	-10000	0	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.012	0.068	-10000	0	-0.28	19	19
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.014	0.074	-10000	0	-0.44	4	4
CHUK	0.021	0.072	0.23	4	-0.38	3	7
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.051	0.034	-10000	0	-0.29	1	1
TCRz/NEF	-0.001	0.096	-10000	0	-0.4	25	25
TNF	0.012	0.079	0.23	1	-0.53	10	11
FASLG	-0.018	0.14	-10000	0	-0.58	26	26
NFKB1	0.022	0.012	-10000	0	-10000	0	0
TNFR1A/BAG4/TNF-alpha	0.028	0.053	0.25	1	-0.33	8	9
CASP6	0.018	0.13	-10000	0	-0.51	14	14
CASP7	0.017	0.11	0.36	6	-0.48	10	16
RELA	0.022	0.016	-10000	0	-10000	0	0
CASP2	0.022	0.004	-10000	0	-10000	0	0
CASP3	0.011	0.11	0.36	6	-0.53	7	13
TNFRSF1A	0.021	0.006	-10000	0	-10000	0	0
TNFR1A/BAG4	0.026	0.018	0.27	1	-10000	0	1
CASP8	0.022	0.004	-10000	0	-10000	0	0
CASP9	0.022	0.005	-10000	0	-10000	0	0
MAP3K14	0.022	0.078	-10000	0	-0.4	4	4
APAF-1/Caspase 9	0.013	0.067	-10000	0	-0.38	6	6
BCL2	0.008	0.12	0.32	3	-0.54	15	18

×

Class I PI3K signaling events

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
ARF5/GTP	-0.009	0.047	-10000	0	-10000	0	0
DAPP1	-0.011	0.12	0.23	2	-0.39	31	33
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.022	0.17	-10000	0	-0.55	34	34
mol:DAG	0.001	0.086	0.2	12	-0.24	21	33
HRAS	0.024	0.008	-10000	0	-10000	0	0
RAP1A	0.024	0.008	-10000	0	-10000	0	0
ARF5/GDP	0.016	0.082	-10000	0	-0.37	11	11
PLCG2	0.022	0.005	-10000	0	-10000	0	0
PLCG1	0.022	0.004	-10000	0	-10000	0	0
ARF5	0.022	0.004	-10000	0	-10000	0	0
mol:GTP	-0.007	0.044	-10000	0	-0.26	2	2
ARF1/GTP	-0.004	0.039	0.23	1	-0.26	2	3
RHOA	0.021	0.007	-10000	0	-10000	0	0
YES1	0.021	0.006	-10000	0	-10000	0	0
RAP1A/GTP	-0.006	0.048	0.3	1	-0.25	2	3
ADAP1	-0.011	0.049	-10000	0	-0.27	6	6
ARAP3	-0.007	0.044	-10000	0	-0.26	2	2
INPPL1	0.022	0.005	-10000	0	-10000	0	0
PREX1	0.016	0.061	-10000	0	-0.53	6	6
ARHGEF6	0.004	0.1	-10000	0	-0.53	17	17
ARHGEF7	0.021	0.006	-10000	0	-10000	0	0
ARF1	0.022	0.004	-10000	0	-10000	0	0
NRAS	0.023	0.009	-10000	0	-10000	0	0
FYN	0.021	0.025	-10000	0	-0.53	1	1
ARF6	0.022	0.005	-10000	0	-10000	0	0
FGR	-0.014	0.14	-10000	0	-0.53	32	32
mol:Ca2+	0.005	0.055	0.19	10	-10000	0	10
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.021	0.025	-10000	0	-0.53	1	1
ZAP70	0.013	0.07	-10000	0	-0.53	8	8
mol:IP3	0.003	0.071	0.18	33	-0.19	11	44
LYN	0.02	0.035	-10000	0	-0.53	2	2
ARF1/GDP	0.015	0.083	-10000	0	-0.35	13	13
RhoA/GDP	0.022	0.059	0.29	3	-0.32	1	4
PDK1/Src/Hsp90	0.042	0.014	-10000	0	-10000	0	0
BLNK	0.021	0.025	-10000	0	-0.53	1	1
actin cytoskeleton reorganization	0.009	0.088	0.29	7	-0.39	6	13
SRC	0.022	0.004	-10000	0	-10000	0	0
PLEKHA2	-0.01	0.005	-10000	0	-10000	0	0
RAC1	0.022	0.004	-10000	0	-10000	0	0
PTEN	0.018	0.014	-10000	0	-10000	0	0
HSP90AA1	0.022	0.005	-10000	0	-10000	0	0
ARF6/GTP	-0.011	0.044	-10000	0	-10000	0	0
RhoA/GTP	-0.007	0.048	0.29	1	-10000	0	1
Src family/SYK family/BLNK-LAT	-0.009	0.11	-10000	0	-0.41	22	22
BLK	0.013	0.088	0.23	12	-0.53	11	23
PDPK1	0.022	0.004	-10000	0	-10000	0	0
CYTH1	-0.009	0.042	-10000	0	-0.25	2	2
HCK	0.018	0.043	-10000	0	-0.53	3	3
CYTH3	-0.009	0.042	-10000	0	-0.25	2	2
CYTH2	-0.01	0.042	-10000	0	-10000	0	0
KRAS	0.022	0.009	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.014	0.032	-10000	0	-10000	0	0
SGK1	0.018	0.032	-10000	0	-10000	0	0
INPP5D	0.021	0.025	-10000	0	-0.53	1	1
mol:GDP	0.004	0.084	0.18	1	-0.35	15	16
SOS1	0.022	0.004	-10000	0	-10000	0	0
SYK	0.022	0.004	-10000	0	-10000	0	0
ARF6/GDP	-0.004	0.059	0.29	3	-0.34	1	4
mol:PI-3-4-5-P3	-0.009	0.04	-10000	0	-0.26	2	2
ARAP3/RAP1A/GTP	-0.006	0.048	0.3	1	-0.26	2	3
VAV1	0.019	0.043	-10000	0	-0.53	3	3
mol:PI-3-4-P2	-0.01	0.017	-10000	0	-0.39	1	1
RAS family/GTP/PI3K Class I	0.039	0.049	-10000	0	-0.26	2	2
PLEKHA1	-0.012	0.015	-10000	0	-0.34	1	1
Rac1/GDP	0.014	0.083	-10000	0	-0.36	12	12
LAT	0.022	0.003	-10000	0	-10000	0	0
Rac1/GTP	0.003	0.083	-10000	0	-0.37	18	18
ITK	-0.023	0.071	-10000	0	-0.28	23	23
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.006	0.11	0.26	8	-0.33	25	33
LCK	0.021	0.025	-10000	0	-0.53	1	1
BTK	-0.029	0.079	-10000	0	-0.28	32	32

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.02	0.025	-10000	0	-0.53	1	1
mol:S1P	0	0.002	-10000	0	-10000	0	0
S1P1/S1P/Gi	0.003	0.055	-10000	0	-0.26	13	13
GNAO1	0.022	0.029	0.23	2	-0.53	1	3
S1P/S1P3/G12/G13	0.042	0.013	-10000	0	-10000	0	0
AKT1	0.013	0.079	-10000	0	-0.45	13	13
AKT3	0.011	0.11	-10000	0	-1.2	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.02	0.025	-10000	0	-0.53	1	1
GNAI2	0.021	0.008	-10000	0	-10000	0	0
GNAI3	0.022	0.007	-10000	0	-10000	0	0
GNAI1	0.021	0.026	-10000	0	-0.53	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
S1PR3	0.023	0.007	-10000	0	-10000	0	0
S1PR2	0.022	0.004	-10000	0	-10000	0	0
EDG1	0	0	-10000	0	-10000	0	0
mol:Ca2+	0.019	0.041	-10000	0	-0.25	3	3
MAPK3	0.009	0.044	-10000	0	-10000	0	0
MAPK1	0.008	0.039	-10000	0	-10000	0	0
JAK2	0.011	0.05	-10000	0	-0.26	2	2
CXCR4	0.008	0.048	-10000	0	-0.33	3	3
FLT1	0.022	0.008	-10000	0	-10000	0	0
RhoA/GDP	0.015	0.005	-10000	0	-10000	0	0
Rac1/GDP	0.016	0.003	-10000	0	-10000	0	0
SRC	0.009	0.043	-10000	0	-0.24	2	2
S1P/S1P3/Gi	0.019	0.041	-10000	0	-0.25	3	3
RAC1	0.022	0.004	-10000	0	-10000	0	0
RhoA/GTP	0.02	0.055	-10000	0	-10000	0	0
VEGFA	0.023	0.006	-10000	0	-10000	0	0
S1P/S1P2/Gi	0.019	0.034	-10000	0	-0.21	4	4
VEGFR1 homodimer/VEGFA homodimer	0.034	0.013	-10000	0	-10000	0	0
RHOA	0.021	0.007	-10000	0	-10000	0	0
S1P/S1P3/Gq	-0.048	0.12	-10000	0	-0.26	117	117
GNAQ	0.021	0.025	-10000	0	-0.53	1	1
GNAZ	0.016	0.056	-10000	0	-0.53	5	5
G12/G13	0.032	0.008	-10000	0	-10000	0	0
GNA14	-0.11	0.24	-10000	0	-0.53	117	117
GNA15	0.022	0.004	-10000	0	-10000	0	0
GNA12	0.022	0.004	-10000	0	-10000	0	0
GNA13	0.022	0.003	-10000	0	-10000	0	0
GNA11	0.022	0.004	-10000	0	-10000	0	0
Rac1/GTP	0.017	0.058	-10000	0	-0.24	1	1

×

Signaling events mediated by PRL

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
CCNE1	0.077	0.11	0.27	110	-10000	0	110
mol:Halofuginone	0.002	0	-10000	0	-10000	0	0
ITGA1	0.015	0.056	-10000	0	-0.53	5	5
CDKN1A	0.009	0.039	-10000	0	-0.31	6	6
PRL-3/alpha Tubulin	0.031	0.009	-10000	0	-10000	0	0
mol:Ca2+	-0.034	0.078	-10000	0	-0.4	22	22
AGT	-0.003	0.12	0.23	1	-0.53	23	24
CCNA2	-0.017	0.047	0.39	1	-10000	0	1
TUBA1B	0.023	0.002	-10000	0	-10000	0	0
EGR1	0.003	0.052	-10000	0	-0.38	9	9
CDK2/Cyclin E1	0.064	0.096	0.33	4	-0.35	4	8
MAPK3	-0.009	0.003	-10000	0	-10000	0	0
PRL-2 /Rab GGTase beta	0.032	0.007	-10000	0	-10000	0	0
MAPK1	-0.009	0.003	-10000	0	-10000	0	0
PTP4A1	-0.01	0.035	-10000	0	-10000	0	0
PTP4A3	0.021	0.006	-10000	0	-10000	0	0
PTP4A2	0.022	0.004	-10000	0	-10000	0	0
ITGB1	-0.009	0.003	-10000	0	-10000	0	0
SRC	0.022	0.004	-10000	0	-10000	0	0
RAC1	0.01	0.03	-10000	0	-0.31	3	3
Rab GGTase beta/Rab GGTase alpha	0.031	0.009	-10000	0	-10000	0	0
PRL-1/ATF-5	0.02	0.055	0.3	1	-10000	0	1
RABGGTA	0.022	0.005	-10000	0	-10000	0	0
BCAR1	-0.017	0.006	-10000	0	-10000	0	0
RHOC	0.005	0.048	-10000	0	-0.31	10	10
RHOA	0.005	0.048	-10000	0	-0.31	10	10
cell motility	0.01	0.064	-10000	0	-0.28	10	10
PRL-1/alpha Tubulin	0.018	0.053	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	0.025	0.044	-10000	0	-0.39	5	5
ROCK1	0.017	0.05	-10000	0	-0.33	3	3
RABGGTB	0.022	0.004	-10000	0	-10000	0	0
CDK2	0.023	0.002	-10000	0	-10000	0	0
mitosis	-0.009	0.034	-10000	0	-10000	0	0
ATF5	0.025	0.025	0.23	7	-10000	0	7

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0.045	0.077	0.2	4	-0.29	4	8
adherens junction organization	0.014	0.098	-10000	0	-0.41	17	17
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.061	0.087	0.26	7	-10000	0	7
FMN1	0.009	0.1	-10000	0	-0.34	23	23
mol:IP3	0.002	0.036	-10000	0	-0.25	3	3
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.031	0.081	-10000	0	-0.41	11	11
CTNNB1	0.022	0.007	-10000	0	-10000	0	0
AKT1	0.002	0.042	-10000	0	-0.29	2	2
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.003	0.15	-10000	0	-0.72	17	17
CTNND1	0.026	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.023	0.079	-10000	0	-0.38	11	11
VASP	0.027	0.073	-10000	0	-0.38	8	8
ZYX	0.025	0.08	-10000	0	-0.39	11	11
JUB	0.026	0.082	-10000	0	-0.34	16	16
EGFR(dimer)	0.035	0.097	0.27	10	-0.37	12	22
E-cadherin/beta catenin-gamma catenin	0.038	0.014	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.011	0.051	-10000	0	-0.26	11	11
PIK3CA	0.013	0.012	-10000	0	-10000	0	0
PI3K	0.011	0.052	-10000	0	-0.26	11	11
FYN	0.04	0.078	0.21	5	-0.3	3	8
mol:Ca2+	0.003	0.037	-10000	0	-0.24	3	3
JUP	0.024	0.005	-10000	0	-10000	0	0
PIK3R1	0.024	0.008	-10000	0	-10000	0	0
mol:DAG	0.002	0.036	-10000	0	-0.25	3	3
CDH1	0.023	0.006	-10000	0	-10000	0	0
RhoA/GDP	0.063	0.086	0.3	4	-10000	0	4
establishment of polarity of embryonic epithelium	0.026	0.074	-10000	0	-0.37	9	9
SRC	0.022	0.004	-10000	0	-10000	0	0
RAC1	0.022	0.004	-10000	0	-10000	0	0
RHOA	0.021	0.007	-10000	0	-10000	0	0
EGFR	0.023	0.081	0.36	12	-0.53	6	18
CASR	0.038	0.076	0.2	4	-10000	0	4
RhoA/GTP	0.059	0.069	-10000	0	-10000	0	0
AKT2	0.002	0.044	-10000	0	-0.28	3	3
actin cable formation	0.005	0.094	-10000	0	-0.39	12	12
apoptosis	-0.049	0.084	0.3	9	-0.22	8	17
CTNNA1	0.025	0.008	-10000	0	-10000	0	0
mol:GDP	0.049	0.086	0.32	3	-0.26	6	9
PIP5K1A	0.023	0.079	-10000	0	-0.4	10	10
PLCG1	0.002	0.036	-10000	0	-0.25	3	3
Rac1/GTP	0.039	0.092	0.29	4	-0.35	11	15
homophilic cell adhesion	0.003	0.004	-10000	0	-10000	0	0

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	-0.031	0.06	0.41	5	-0.24	1	6
KIRREL	0.015	0.07	-10000	0	-0.53	8	8
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.031	0.06	0.24	1	-0.42	5	6
PLCG1	0.022	0.004	-10000	0	-10000	0	0
ARRB2	0.022	0.005	-10000	0	-10000	0	0
WASL	0.022	0.004	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	0.049	0.055	0.32	1	-0.32	5	6
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.013	0.036	-10000	0	-0.28	3	3
FYN	0.009	0.078	0.29	18	-0.34	5	23
mol:Ca2+	0.046	0.049	0.31	1	-0.3	3	4
mol:DAG	0.047	0.05	0.31	1	-0.3	3	4
NPHS2	-0.004	0.031	0.25	3	-10000	0	3
mol:IP3	0.047	0.05	0.31	1	-0.3	3	4
regulation of endocytosis	0.039	0.051	-10000	0	-0.31	5	5
Nephrin/NEPH1/podocin/Cholesterol	0.036	0.052	0.25	2	-0.32	5	7
establishment of cell polarity	0.031	0.06	0.24	1	-0.41	5	6
Nephrin/NEPH1/podocin/NCK1-2	0.05	0.057	0.31	1	-0.3	5	6
Nephrin/NEPH1/beta Arrestin2	0.042	0.053	-10000	0	-0.32	5	5
NPHS1	0.024	0.058	0.26	24	-10000	0	24
Nephrin/NEPH1/podocin	0.038	0.055	0.3	1	-0.34	5	6
TJP1	0.022	0.004	-10000	0	-10000	0	0
NCK1	0.019	0.008	-10000	0	-10000	0	0
NCK2	0.023	0.002	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.048	0.051	0.32	1	-0.31	3	4
CD2AP	0.022	0.004	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	0.049	0.053	0.32	1	-0.32	4	5
GRB2	0.022	0.004	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.012	0.1	0.28	15	-0.35	23	38
cytoskeleton organization	-0.002	0.042	0.19	7	-0.33	3	10
Nephrin/NEPH1	0.027	0.045	0.19	1	-0.29	5	6
Nephrin/NEPH1/ZO-1	0.041	0.052	-10000	0	-0.33	5	5

×

EPO 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.04	0.048	-10000	0	-10000	0	0
CRKL	0.011	0.063	0.3	8	-0.26	1	9
mol:DAG	0.026	0.037	-10000	0	-0.31	1	1
HRAS	0.015	0.075	0.28	15	-10000	0	15
MAPK8	0.003	0.051	0.18	18	-0.32	1	19
RAP1A	0.011	0.068	0.33	9	-0.26	2	11
GAB1	0.012	0.069	0.33	9	-0.26	1	10
MAPK14	0.004	0.054	0.19	16	-0.32	1	17
EPO	0.025	0.027	0.25	6	-10000	0	6
PLCG1	0.026	0.038	-10000	0	-0.32	1	1
EPOR/TRPC2/IP3 Receptors	0.025	0.009	-10000	0	-10000	0	0
RAPGEF1	0.022	0.003	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.044	0.035	-10000	0	-0.35	2	2
GAB1/SHC/GRB2/SOS1	0.046	0.048	0.26	5	-10000	0	5
EPO/EPOR (dimer)	0.036	0.023	0.23	1	-10000	0	1
IRS2	0.008	0.067	0.3	8	-0.27	4	12
STAT1	0.031	0.037	-10000	0	-10000	0	0
STAT5B	0.029	0.039	-10000	0	-0.32	1	1
cell proliferation	0.001	0.052	0.19	19	-0.3	1	20
GAB1/SHIP/PIK3R1/SHP2/SHC	0.035	0.037	-10000	0	-10000	0	0
TEC	0.01	0.069	0.33	8	-0.27	4	12
SOCS3	0.02	0.035	-10000	0	-0.53	2	2
STAT1 (dimer)	0.03	0.036	-10000	0	-10000	0	0
JAK2	0.023	0.012	-10000	0	-10000	0	0
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.06	0.049	0.33	1	-0.27	2	3
EPO/EPOR	0.036	0.023	0.23	1	-10000	0	1
LYN	0.021	0.035	-10000	0	-0.53	2	2
TEC/VAV2	0.033	0.061	0.27	6	-0.34	4	10
elevation of cytosolic calcium ion concentration	0.025	0.009	-10000	0	-10000	0	0
SHC1	0.022	0.005	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	0.047	0.031	0.22	1	-0.35	1	2
mol:IP3	0.026	0.037	-10000	0	-0.31	1	1
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.041	0.06	0.29	7	-10000	0	7
SH2B3	0.024	0.036	-10000	0	-0.54	2	2
NFKB1	0.005	0.054	0.18	21	-0.32	1	22
EPO/EPOR (dimer)/JAK2/SOCS3	0.009	0.032	0.25	2	-0.2	6	8
PTPN6	0.015	0.046	0.3	2	-0.27	2	4
TEC/VAV2/GRB2	0.042	0.06	0.27	6	-0.42	2	8
EPOR	0.025	0.009	-10000	0	-10000	0	0
INPP5D	0.021	0.025	-10000	0	-0.53	1	1
mol:GDP	0.046	0.048	0.26	5	-10000	0	5
SOS1	0.022	0.004	-10000	0	-10000	0	0
PLCG2	0.022	0.005	-10000	0	-10000	0	0
CRKL/CBL/C3G	0.044	0.051	0.27	6	-10000	0	6
VAV2	0.01	0.068	0.3	8	-0.29	4	12
CBL	0.012	0.069	0.33	9	-0.26	2	11
SHC/Grb2/SOS1	0.029	0.029	-10000	0	-10000	0	0
STAT5A	0.029	0.039	-10000	0	-0.32	1	1
GRB2	0.022	0.004	-10000	0	-10000	0	0
STAT5 (dimer)	0.043	0.043	-10000	0	-10000	0	0
LYN/PLCgamma2	0.03	0.028	-10000	0	-0.39	2	2
PTPN11	0.023	0.002	-10000	0	-10000	0	0
BTK	-0.01	0.1	0.33	8	-0.29	36	44
BCL2	0.041	0.051	-10000	0	-10000	0	0

×

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
SPHK2	-0.011	0.017	-10000	0	-0.39	1	1
MAP4K4	0.006	0.061	-10000	0	-0.46	2	2
BAG4	0.019	0.018	0.38	1	-10000	0	1
PKC zeta/ceramide	0.012	0.043	-10000	0	-0.22	11	11
NFKBIA	0.022	0.005	-10000	0	-10000	0	0
BIRC3	0.015	0.061	-10000	0	-0.53	6	6
BAX	0.001	0.056	-10000	0	-0.33	13	13
RIPK1	0.022	0.004	-10000	0	-10000	0	0
AKT1	0.014	0.12	0.66	17	-10000	0	17
BAD	-0.004	0.042	0.19	2	-0.22	11	13
SMPD1	0.007	0.054	0.19	4	-0.2	11	15
RB1	-0.005	0.043	0.18	2	-0.23	12	14
FADD/Caspase 8	0.023	0.08	-10000	0	-0.44	3	3
MAP2K4	-0.006	0.041	0.19	2	-0.61	1	3
NSMAF	0.022	0.005	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.002	0.048	0.2	13	-0.32	2	15
EGF	0.015	0.068	0.23	3	-0.53	7	10
mol:ceramide	-0.002	0.043	0.16	1	-0.24	11	12
MADD	0.022	0.004	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.009	0.003	-10000	0	-10000	0	0
ASAH1	0.021	0.007	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.005	0.042	0.18	2	-0.22	12	14
cell proliferation	0.01	0.062	-10000	0	-0.25	12	12
BID	0.001	0.12	-10000	0	-0.61	16	16
MAP3K1	-0.005	0.041	0.18	2	-0.22	11	13
EIF2A	0.046	0.095	0.3	20	-0.26	1	21
TRADD	0.022	0.005	-10000	0	-10000	0	0
CRADD	0.023	0.002	-10000	0	-10000	0	0
MAPK3	-0.002	0.047	0.23	4	-0.42	1	5
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.002	0.045	0.24	3	-0.43	1	4
Cathepsin D/ceramide	0.012	0.043	-10000	0	-0.22	11	11
FADD	0.004	0.055	-10000	0	-0.46	2	2
KSR1	0	0.048	0.2	13	-0.21	11	24
MAPK8	-0.005	0.052	-10000	0	-0.3	4	4
PRKRA	0.001	0.052	0.19	15	-0.24	9	24
PDGFA	0.021	0.025	-10000	0	-0.53	1	1
TRAF2	0.022	0.004	-10000	0	-10000	0	0
IGF1	0.003	0.1	0.23	1	-0.53	18	19
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.002	0.042	0.16	1	-0.23	11	12
CTSD	0.022	0.004	-10000	0	-10000	0	0
regulation of nitric oxide biosynthetic process	0.032	0.008	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	0.011	0.066	-10000	0	-0.28	7	7
PRKCD	0.021	0.007	-10000	0	-10000	0	0
PRKCZ	0.022	0.005	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.009	0.003	-10000	0	-10000	0	0
RelA/NF kappa B1	0.032	0.008	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.023	0.002	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.007	0.053	-10000	0	-0.48	2	2
TNFR1A/BAG4/TNF-alpha	0.028	0.053	0.25	1	-0.33	8	9
mol:Sphingosine-1-phosphate	-0.011	0.017	-10000	0	-0.39	1	1
MAP2K1	-0.005	0.046	0.23	4	-0.43	1	5
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.023	0.002	-10000	0	-10000	0	0
CYCS	-0.001	0.044	-10000	0	-0.21	12	12
TNFRSF1A	0.021	0.006	-10000	0	-10000	0	0
NFKB1	0.022	0.005	-10000	0	-10000	0	0
TNFR1A/BAG4	0.026	0.018	0.27	1	-10000	0	1
EIF2AK2	0.001	0.051	0.19	21	-0.44	1	22
TNF-alpha/TNFR1A/FAN	0.034	0.049	-10000	0	-0.34	7	7
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.011	0.081	-10000	0	-0.47	6	6
MAP2K2	-0.005	0.046	0.25	3	-0.43	1	4
SMPD3	0.003	0.074	0.18	2	-0.29	21	23
TNF	0.012	0.079	0.23	1	-0.53	10	11
PKC zeta/PAR4	0.032	0.008	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	0.005	0.041	0.23	7	-0.19	3	10
NF kappa B1/RelA/I kappa B alpha	0.059	0.023	-10000	0	-10000	0	0
AIFM1	0	0.041	-10000	0	-0.2	9	9
BCL2	0.023	0.016	0.38	1	-10000	0	1

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.022	0.004	-10000	0	-10000	0	0
HDAC4	0.022	0.004	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.009	0.021	-10000	0	-0.3	2	2
CDKN1A	-0.009	0.006	-10000	0	-10000	0	0
KAT2B	0.021	0.006	-10000	0	-10000	0	0
BAX	0.022	0.004	-10000	0	-10000	0	0
FOXO3	-0.004	0.003	-10000	0	-10000	0	0
FOXO1	0.021	0.006	-10000	0	-10000	0	0
FOXO4	0.01	0.003	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.022	0.004	-10000	0	-10000	0	0
TAT	0.016	0.024	0.3	2	-10000	0	2
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.019	0.024	0.3	1	-10000	0	1
PPARGC1A	-0.076	0.21	-10000	0	-0.53	87	87
FHL2	0.024	0.019	0.23	4	-10000	0	4
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.03	0.008	-10000	0	-10000	0	0
HIST2H4A	-0.009	0.021	0.3	2	-10000	0	2
SIRT1/FOXO3a	0.011	0.03	-10000	0	-0.2	9	9
SIRT1	0.02	0.004	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.041	0.014	-10000	0	-10000	0	0
SIRT1/Histone H1b	0.019	0.035	-10000	0	-0.2	5	5
apoptosis	-0.041	0.012	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.04	0.14	-10000	0	-0.33	87	87
p53/SIRT1	0.024	0.02	-10000	0	-0.39	1	1
SIRT1/FOXO4	0.019	0.032	-10000	0	-0.19	4	4
FOXO1/FHL2/SIRT1	0.04	0.017	-10000	0	-10000	0	0
HIST1H1E	0.013	0.012	0.16	1	-10000	0	1
SIRT1/p300	0.03	0.008	-10000	0	-10000	0	0
muscle cell differentiation	-0.014	0.036	-10000	0	-10000	0	0
TP53	0.018	0.025	-10000	0	-0.53	1	1
KU70/SIRT1/BAX	0.041	0.012	-10000	0	-10000	0	0
CREBBP	0.022	0.005	-10000	0	-10000	0	0
MEF2D	0.022	0.005	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.03	0.015	0.26	1	-10000	0	1
ACSS2	-0.01	0.003	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	0.014	0.037	-10000	0	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.007	0.08	0.24	1	-0.43	7	8
BAG4	0.019	0.018	0.38	1	-10000	0	1
BAD	0.003	0.033	0.16	3	-10000	0	3
NFKBIA	0.022	0.005	-10000	0	-10000	0	0
BIRC3	0.015	0.061	-10000	0	-0.53	6	6
BAX	0.003	0.032	0.31	1	-10000	0	1
EnzymeConsortium:3.1.4.12	0.004	0.022	0.11	1	-0.093	6	7
IKBKB	0.018	0.088	0.24	1	-0.45	5	6
MAP2K2	0.003	0.039	0.2	10	-10000	0	10
MAP2K1	0.002	0.04	0.2	10	-10000	0	10
SMPD1	0.003	0.028	0.11	1	-0.13	7	8
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.033	0.098	0.26	16	-0.48	4	20
MAP2K4	0.003	0.026	0.17	1	-10000	0	1
protein ubiquitination	0.012	0.082	-10000	0	-0.42	6	6
EnzymeConsortium:2.7.1.37	0.001	0.042	0.2	10	-10000	0	10
response to UV	0	0	0.002	11	-10000	0	11
RAF1	0.006	0.04	0.2	11	-10000	0	11
CRADD	0.023	0.002	-10000	0	-10000	0	0
mol:ceramide	0.005	0.033	0.13	2	-0.14	7	9
I-kappa-B-alpha/RELA/p50/ubiquitin	0.029	0.007	-10000	0	-10000	0	0
MADD	0.022	0.004	-10000	0	-10000	0	0
MAP3K1	0.004	0.029	0.16	2	-10000	0	2
TRADD	0.022	0.005	-10000	0	-10000	0	0
RELA/p50	0.023	0.002	-10000	0	-10000	0	0
MAPK3	0.003	0.044	0.2	10	-10000	0	10
MAPK1	0.003	0.042	0.2	9	-10000	0	9
p50/RELA/I-kappa-B-alpha	0.032	0.008	-10000	0	-10000	0	0
FADD	0.028	0.096	0.26	13	-0.48	4	17
KSR1	0.006	0.042	0.19	12	-10000	0	12
MAPK8	0	0.028	0.16	3	-10000	0	3
TRAF2	0.022	0.004	-10000	0	-10000	0	0
response to radiation	0	0	0.002	3	-10000	0	3
CHUK	0.008	0.076	-10000	0	-0.45	5	5
TNF R/SODD	0.026	0.018	0.27	1	-10000	0	1
TNF	0.012	0.079	0.23	1	-0.53	10	11
CYCS	0.002	0.037	0.26	1	-0.22	2	3
IKBKG	0.009	0.079	0.26	1	-0.42	5	6
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.01	0.081	-10000	0	-0.47	6	6
RELA	0.023	0.002	-10000	0	-10000	0	0
RIPK1	0.022	0.004	-10000	0	-10000	0	0
AIFM1	0.002	0.033	0.22	1	-0.18	1	2
TNF/TNF R/SODD	0.028	0.053	0.25	1	-0.33	8	9
TNFRSF1A	0.021	0.006	-10000	0	-10000	0	0
response to heat	0	0	0.002	3	-10000	0	3
CASP8	0.016	0.08	-10000	0	-0.55	9	9
NSMAF	0.011	0.078	0.26	3	-0.43	6	9
response to hydrogen peroxide	0	0	0.002	11	-10000	0	11
BCL2	0.023	0.016	0.38	1	-10000	0	1

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	0.048	0.039	-10000	0	-0.31	4	4
HDAC3	0.021	0.006	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.01	0.004	-10000	0	-10000	0	0
GATA1/HDAC4	-0.006	0.12	-10000	0	-0.39	44	44
GATA1/HDAC5	-0.006	0.12	-10000	0	-0.39	43	43
GATA2/HDAC5	-0.011	0.12	-10000	0	-0.39	47	47
HDAC5/BCL6/BCoR	0.027	0.023	-10000	0	-10000	0	0
HDAC9	0.022	0.03	0.23	3	-0.53	1	4
Glucocorticoid receptor/Hsp90/HDAC6	0.041	0.015	-10000	0	-10000	0	0
HDAC4/ANKRA2	0.031	0.01	-10000	0	-10000	0	0
HDAC5/YWHAB	0.032	0.008	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.01	0.003	-10000	0	-10000	0	0
GATA2	-0.034	0.16	-10000	0	-0.53	49	49
HDAC4/RFXANK	0.032	0.008	-10000	0	-10000	0	0
BCOR	0.022	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.022	0.005	-10000	0	-10000	0	0
HDAC5	0.022	0.004	-10000	0	-10000	0	0
GNB1/GNG2	0.026	0.047	-10000	0	-0.39	6	6
Histones	0.017	0.036	-10000	0	-0.26	3	3
ADRBK1	0.022	0.004	-10000	0	-10000	0	0
HDAC4	0.022	0.004	-10000	0	-10000	0	0
XPO1	0.021	0.007	-10000	0	-10000	0	0
HDAC5/ANKRA2	0.031	0.01	-10000	0	-10000	0	0
HDAC4/Ubc9	0.032	0.008	-10000	0	-10000	0	0
HDAC7	0.023	0.003	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.031	0.009	-10000	0	-10000	0	0
TUBA1B	0.023	0.002	-10000	0	-10000	0	0
HDAC6	0.022	0.004	-10000	0	-10000	0	0
HDAC5/RFXANK	0.032	0.008	-10000	0	-10000	0	0
CAMK4	0.019	0.036	-10000	0	-0.53	2	2
Tubulin/HDAC6	0.044	0.011	-10000	0	-10000	0	0
SUMO1	0.022	0.003	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.022	0.004	-10000	0	-10000	0	0
GATA1	-0.032	0.16	-10000	0	-0.53	44	44
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.022	0.005	-10000	0	-10000	0	0
NR3C1	0.021	0.006	-10000	0	-10000	0	0
SUMO1/HDAC4	0.031	0.029	-10000	0	-0.24	1	1
SRF	0.022	0.004	-10000	0	-10000	0	0
HDAC4/YWHAB	0.032	0.007	-10000	0	-10000	0	0
Tubulin	0.033	0.006	-10000	0	-10000	0	0
HDAC4/14-3-3 E	0.032	0.009	-10000	0	-10000	0	0
GNB1	0.021	0.025	-10000	0	-0.53	1	1
RANGAP1	0.022	0.004	-10000	0	-10000	0	0
BCL6/BCoR	0.02	0.017	-10000	0	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0.042	0.02	-10000	0	-0.32	1	1
HDAC4/SRF	0.04	0.029	-10000	0	-0.34	2	2
HDAC4/ER alpha	0.013	0.089	-10000	0	-0.39	23	23
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.017	0.036	-10000	0	-0.26	3	3
cell motility	0.043	0.011	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.022	0.004	-10000	0	-10000	0	0
HDAC7/HDAC3	0.031	0.009	-10000	0	-10000	0	0
BCL6	0.014	0.011	-10000	0	-10000	0	0
HDAC4/CaMK II delta B	0.022	0.004	-10000	0	-10000	0	0
Hsp90/HDAC6	0.032	0.008	-10000	0	-10000	0	0
ESR1	-0.003	0.12	-10000	0	-0.53	23	23
HDAC6/HDAC11	0.031	0.01	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.03	0.028	-10000	0	-10000	0	0
NPC	0.013	0.001	-10000	0	-10000	0	0
MEF2C	0.01	0.078	-10000	0	-0.53	10	10
RAN	0.023	0.002	-10000	0	-10000	0	0
HDAC4/MEF2C	0.054	0.054	-10000	0	-0.29	10	10
GNG2	0.016	0.055	-10000	0	-0.53	5	5
NCOR2	0.021	0.025	-10000	0	-0.53	1	1
TUBB2A	0.022	0.004	-10000	0	-10000	0	0
HDAC11	0.021	0.006	-10000	0	-10000	0	0
HSP90AA1	0.022	0.005	-10000	0	-10000	0	0
RANBP2	0.023	0.002	-10000	0	-10000	0	0
ANKRA2	0.021	0.006	-10000	0	-10000	0	0
RFXANK	0.022	0.004	-10000	0	-10000	0	0
nuclear import	-0.026	0.009	-10000	0	-10000	0	0

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.033	0.007	-10000	0	-10000	0	0
ATM	0.022	0.004	-10000	0	-10000	0	0
UBE2D3	0.022	0.005	-10000	0	-10000	0	0
PRKDC	0.022	0.005	-10000	0	-10000	0	0
ATR	0.018	0.009	-10000	0	-10000	0	0
UBE2L3	0.021	0.006	-10000	0	-10000	0	0
FANCD2	0.012	0.007	-10000	0	-10000	0	0
protein ubiquitination	0.08	0.057	-10000	0	-10000	0	0
XRCC5	0.022	0.004	-10000	0	-10000	0	0
XRCC6	0.022	0.004	-10000	0	-10000	0	0
M/R/N Complex	0.041	0.015	-10000	0	-10000	0	0
MRE11A	0.022	0.004	-10000	0	-10000	0	0
DNA-PK	0.043	0.013	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.012	0.1	0.3	1	-0.52	13	14
FANCF	0.022	0.004	-10000	0	-10000	0	0
BRCA1	0.022	0.003	-10000	0	-10000	0	0
CCNE1	0.077	0.11	0.27	110	-10000	0	110
CDK2/Cyclin E1	0.069	0.073	0.27	32	-10000	0	32
FANCG	0.022	0.024	0.38	2	-10000	0	2
BRCA1/BACH1/BARD1	0.032	0.007	-10000	0	-10000	0	0
FANCE	0.022	0.003	-10000	0	-10000	0	0
FANCC	0.022	0.004	-10000	0	-10000	0	0
NBN	0.022	0.005	-10000	0	-10000	0	0
FANCA	0.023	0.019	0.3	2	-10000	0	2
DNA repair	0.014	0.081	0.28	8	-0.41	6	14
BRCA1/BARD1/ubiquitin	0.032	0.007	-10000	0	-10000	0	0
BARD1/DNA-PK	0.054	0.016	-10000	0	-10000	0	0
FANCL	0.022	0.017	0.38	1	-10000	0	1
mRNA polyadenylation	-0.033	0.006	-10000	0	-10000	0	0
BRCA1/BARD1/CTIP/M/R/N Complex	0.02	0.033	0.21	1	-0.27	1	2
BRCA1/BACH1/BARD1/TopBP1	0.039	0.017	-10000	0	-10000	0	0
BRCA1/BARD1/P53	0.043	0.03	-10000	0	-0.31	1	1
BARD1/CSTF1/BRCA1	0.044	0.011	-10000	0	-10000	0	0
BRCA1/BACH1	0.022	0.003	-10000	0	-10000	0	0
BARD1	0.022	0.004	-10000	0	-10000	0	0
PCNA	0.022	0.005	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	0.043	0.013	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH7	0.041	0.015	-10000	0	-10000	0	0
BRCA1/BARD1/RAD51/PCNA	0.07	0.048	-10000	0	-10000	0	0
BARD1/DNA-PK/P53	0.059	0.028	-10000	0	-0.29	1	1
BRCA1/BARD1/Ubiquitin	0.032	0.007	-10000	0	-10000	0	0
BRCA1/BARD1/CTIP	0.033	0.012	-10000	0	-10000	0	0
FA complex	0.032	0.041	0.41	1	-0.26	2	3
BARD1/EWS	0.032	0.008	-10000	0	-10000	0	0
RBBP8	-0.009	0.014	0.3	1	-10000	0	1
TP53	0.02	0.025	-10000	0	-0.53	1	1
TOPBP1	0.02	0.008	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.041	0.029	0.31	1	-10000	0	1
BRCA1/BARD1	0.089	0.062	-10000	0	-10000	0	0
CSTF1	0.022	0.003	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.017	0.003	-10000	0	-10000	0	0
CDK2	0.023	0.002	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.053	0.073	0.23	72	-10000	0	72
RAD50	0.021	0.006	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.032	0.007	-10000	0	-10000	0	0
EWSR1	0.022	0.004	-10000	0	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.022	0.004	-9999	-10000	0	0
ITGB7	0.021	0.025	-9999	-0.53	1	1
ITGA4	0.016	0.061	-9999	-0.53	6	6
alpha4/beta7 Integrin	0.027	0.05	-9999	-0.39	7	7
alpha4/beta1 Integrin	0.027	0.047	-9999	-0.39	6	6

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.013	0.011	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0.009	0.054	-10000	0	-0.39	6	6
MAP2K4	0.012	0.031	-10000	0	-10000	0	0
IKBKB	0.021	0.017	0.38	1	-10000	0	1
TNFRSF10B	0.02	0.007	-10000	0	-10000	0	0
TNFRSF10A	0.019	0.026	-10000	0	-0.53	1	1
SMPD1	0.006	0.005	-10000	0	-10000	0	0
IKBKG	0.022	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.001	0.1	-10000	0	-0.53	17	17
TRAIL/TRAILR2	0.018	0.017	-10000	0	-10000	0	0
TRAIL/TRAILR3	-0.007	0.087	-10000	0	-0.39	18	18
TRAIL/TRAILR1	0.017	0.026	-10000	0	-0.39	1	1
TRAIL/TRAILR4	0.009	0.055	-10000	0	-0.39	6	6
TRAIL/TRAILR1/DAP3/GTP	0.022	0.027	-10000	0	-0.31	1	1
IKK complex	0.007	0.03	-10000	0	-10000	0	0
RIPK1	0.022	0.004	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.016	0.004	-10000	0	-10000	0	0
MAPK3	-0.006	0.005	-10000	0	-10000	0	0
MAP3K1	0.017	0.029	-10000	0	-10000	0	0
TRAILR4 (trimer)	0.001	0.1	-10000	0	-0.53	17	17
TRADD	0.022	0.005	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.019	0.026	-10000	0	-0.53	1	1
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.009	0.024	-10000	0	-0.28	2	2
CFLAR	0.022	0.004	-10000	0	-10000	0	0
MAPK1	-0.006	0.005	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP	0.03	0.037	-10000	0	-0.29	1	1
mol:ceramide	0.006	0.005	-10000	0	-10000	0	0
FADD	0.019	0.008	-10000	0	-10000	0	0
MAPK8	0.043	0.053	0.28	1	-10000	0	1
TRAF2	0.022	0.004	-10000	0	-10000	0	0
TRAILR3 (trimer)	-0.034	0.16	-10000	0	-0.53	49	49
CHUK	0.022	0.005	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	0.02	0.029	-10000	0	-0.34	1	1
DAP3	0.022	0.005	-10000	0	-10000	0	0
CASP10	0.06	0.094	0.36	16	-10000	0	16
JNK cascade	0.009	0.054	-10000	0	-0.39	6	6
TRAIL (trimer)	0.013	0.011	-10000	0	-10000	0	0
TNFRSF10C	-0.034	0.16	-10000	0	-0.53	49	49
TRAIL/TRAILR1/DAP3/GTP/FADD	0.024	0.031	-10000	0	-0.29	1	1
TRAIL/TRAILR2/FADD	0.021	0.023	-10000	0	-10000	0	0
cell death	0.006	0.005	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.01	0.016	-10000	0	-10000	0	0
TRAILR2 (trimer)	0.02	0.007	-10000	0	-10000	0	0
CASP8	-0.005	0.077	-10000	0	-0.49	11	11
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.031	0.034	-10000	0	-10000	0	0

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.017	0.002	-10000	0	-10000	0	0
PRKCZ	0.022	0.005	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.021	0.006	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	0	0.054	-10000	0	-0.36	3	3
IRAK/TOLLIP	0.023	0.006	-10000	0	-10000	0	0
IKBKB	0.021	0.017	0.38	1	-10000	0	1
IKBKG	0.022	0.004	-10000	0	-10000	0	0
IL1 alpha/IL1R2	0.032	0.094	0.31	3	-0.39	18	21
IL1A	0.011	0.11	0.23	21	-0.53	18	39
IL1B	-0.019	0.059	-10000	0	-0.39	12	12
IRAK/TRAF6/p62/Atypical PKCs	0.03	0.029	-10000	0	-10000	0	0
IL1R2	0.035	0.05	0.24	29	-10000	0	29
IL1R1	0.021	0.025	-10000	0	-0.53	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.027	0.057	0.33	1	-0.26	2	3
TOLLIP	0.022	0.004	-10000	0	-10000	0	0
TICAM2	0.015	0.056	-10000	0	-0.53	5	5
MAP3K3	0.022	0.003	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.015	0.002	-10000	0	-10000	0	0
IKK complex/ELKS	0.033	0.047	-10000	0	-10000	0	0
JUN	-0.011	0.026	0.15	12	-10000	0	12
MAP3K7	0.023	0.002	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.022	0.051	-10000	0	-0.28	9	9
IL1 alpha/IL1R1/IL1RAP/MYD88	0.027	0.069	-10000	0	-0.33	11	11
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.033	0.07	-10000	0	-0.31	11	11
IL1 beta fragment/IL1R1/IL1RAP	0.014	0.049	-10000	0	-0.31	9	9
NFKB1	0.022	0.005	-10000	0	-10000	0	0
MAPK8	-0.009	0.028	0.16	13	-10000	0	13
IRAK1	0.01	0.002	-10000	0	-10000	0	0
IL1RN/IL1R1	0.031	0.04	0.27	1	-0.55	2	3
IRAK4	0.023	0.003	-10000	0	-10000	0	0
PRKCI	0.013	0.011	-10000	0	-10000	0	0
TRAF6	0.022	0.004	-10000	0	-10000	0	0
PI3K	0.017	0.017	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.001	0.054	-10000	0	-0.36	3	3
CHUK	0.022	0.005	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.014	0.049	-10000	0	-0.31	9	9
IL1 beta/IL1R2	0.027	0.07	0.3	2	-0.34	13	15
IRAK/TRAF6/TAK1/TAB1/TAB2	0.03	0.008	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.017	0.045	-10000	0	-0.27	7	7
IRAK3	0.009	0.085	-10000	0	-0.53	12	12
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.022	0.062	-10000	0	-0.28	14	14
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.005	0.057	-10000	0	-0.31	11	11
IL1 alpha/IL1R1/IL1RAP	0.021	0.071	-10000	0	-0.36	11	11
RELA	0.023	0.002	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.021	0.006	-10000	0	-10000	0	0
MYD88	0.021	0.006	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0.036	0.01	-10000	0	-10000	0	0
IL1RAP	0.014	0.011	-10000	0	-10000	0	0
UBE2N	0.023	0.002	-10000	0	-10000	0	0
IRAK/TRAF6	0.008	0.049	-10000	0	-10000	0	0
CASP1	0.02	0.035	-10000	0	-0.53	2	2
IL1RN/IL1R2	0.04	0.045	0.27	2	-0.39	2	4
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.02	0.051	-10000	0	-0.29	9	9
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0	0.068	-10000	0	-0.4	6	6
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
IL1RN	0.021	0.039	0.38	1	-0.53	2	3
TRAF6/TAK1/TAB1/TAB2	0.032	0.007	-10000	0	-10000	0	0
MAP2K6	-0.006	0.031	0.17	14	-10000	0	14

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	0.032	0.071	-10000	0	-0.34	9	9
Ran/GTP/Exportin 1/HDAC1	-0.01	0.004	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.016	0.08	-10000	0	-0.32	12	12
SUMO1	0.022	0.003	-10000	0	-10000	0	0
ZFPM1	0.02	0.025	-10000	0	-0.53	1	1
NPC/RanGAP1/SUMO1/Ubc9	0.01	0.003	-10000	0	-10000	0	0
FKBP3	0.022	0.005	-10000	0	-10000	0	0
Histones	0.041	0.063	-10000	0	-10000	0	0
YY1/LSF	0.012	0.062	-10000	0	-0.29	5	5
SMG5	0.022	0.005	-10000	0	-10000	0	0
RAN	0.023	0.002	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	0.012	0.039	-10000	0	-0.26	8	8
I kappa B alpha/HDAC1	0.02	0.055	-10000	0	-0.25	1	1
SAP18	0.021	0.006	-10000	0	-10000	0	0
RELA	0.018	0.048	-10000	0	-0.26	8	8
HDAC1/Smad7	0.041	0.015	-10000	0	-10000	0	0
RANGAP1	0.022	0.004	-10000	0	-10000	0	0
HDAC3/TR2	0.018	0.06	-10000	0	-0.25	1	1
NuRD/MBD3 Complex	0.023	0.043	-10000	0	-0.4	2	2
NF kappa B1 p50/RelA	0.017	0.078	-10000	0	-0.31	11	11
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	-0.034	0.16	-10000	0	-0.53	49	49
GATA1	-0.032	0.16	-10000	0	-0.53	44	44
Mad/Max	0.031	0.009	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	-0.002	0.092	-10000	0	-0.38	10	10
RBBP7	0.022	0.005	-10000	0	-10000	0	0
NPC	0.013	0.001	-10000	0	-10000	0	0
RBBP4	0.022	0.004	-10000	0	-10000	0	0
MAX	0.022	0.004	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.021	0.006	-10000	0	-10000	0	0
NFKBIA	0.011	0.03	-10000	0	-10000	0	0
KAT2B	0.021	0.006	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.014	0.03	-10000	0	-0.36	1	1
SIN3 complex	0.051	0.02	-10000	0	-10000	0	0
SMURF1	0.021	0.006	-10000	0	-10000	0	0
CHD3	0.021	0.005	-10000	0	-10000	0	0
SAP30	0.021	0.006	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.022	0.005	-10000	0	-10000	0	0
YY1/HDAC3	0.011	0.056	-10000	0	-0.36	6	6
YY1/HDAC2	0.013	0.062	-10000	0	-0.3	5	5
YY1/HDAC1	0.013	0.06	-10000	0	-0.29	5	5
NuRD/MBD2 Complex (MeCP1)	0.024	0.036	-10000	0	-10000	0	0
PPARG	-0.018	0.12	-10000	0	-0.33	57	57
HDAC8/hEST1B	0.043	0.013	-10000	0	-10000	0	0
UBE2I	0.022	0.004	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.021	0.006	-10000	0	-10000	0	0
TNFRSF1A	0.021	0.006	-10000	0	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.018	0.062	-10000	0	-0.34	2	2
MBD3L2	-0.017	0.004	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.04	0.015	-10000	0	-10000	0	0
CREBBP	0.022	0.005	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.02	0.061	-10000	0	-0.33	6	6
HDAC1	0.022	0.004	-10000	0	-10000	0	0
HDAC3	0.011	0.03	-10000	0	-10000	0	0
HDAC2	0.023	0.002	-10000	0	-10000	0	0
YY1	0.012	0.01	-10000	0	-10000	0	0
HDAC8	0.023	0.002	-10000	0	-10000	0	0
SMAD7	0.022	0.005	-10000	0	-10000	0	0
NCOR2	0.021	0.025	-10000	0	-0.53	1	1
MXD1	0.022	0.004	-10000	0	-10000	0	0
STAT3	0.015	0.005	-10000	0	-10000	0	0
NFKB1	0.022	0.005	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.023	0.002	-10000	0	-10000	0	0
YY1/LSF/HDAC1	0.025	0.06	-10000	0	-0.26	5	5
YY1/SAP30/HDAC1	0.025	0.058	-10000	0	-0.26	5	5
EP300	0.022	0.004	-10000	0	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.015	0.005	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.011	0.03	-10000	0	-10000	0	0
histone deacetylation	0.024	0.036	-10000	0	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.015	0.032	-10000	0	-0.24	1	1
nuclear export	-0.042	0.013	-10000	0	-10000	0	0
PRKACA	0.022	0.004	-10000	0	-10000	0	0
GATAD2B	0.022	0.005	-10000	0	-10000	0	0
GATAD2A	0.022	0.004	-10000	0	-10000	0	0
GATA2/HDAC3	-0.014	0.12	-10000	0	-0.33	47	47
GATA1/HDAC1	-0.006	0.12	-10000	0	-0.39	44	44
GATA1/HDAC3	-0.011	0.11	-10000	0	-0.31	42	42
CHD4	0.021	0.006	-10000	0	-10000	0	0
TNF-alpha/TNFR1A	0.023	0.056	-10000	0	-0.39	8	8
SIN3/HDAC complex/Mad/Max	0.01	0.058	-10000	0	-0.35	4	4
NuRD Complex	0.021	0.057	-10000	0	-0.33	3	3
positive regulation of chromatin silencing	0.038	0.062	-10000	0	-10000	0	0
SIN3B	0.022	0.004	-10000	0	-10000	0	0
MTA2	0.023	0.002	-10000	0	-10000	0	0
SIN3A	0.023	0.002	-10000	0	-10000	0	0
XPO1	0.021	0.007	-10000	0	-10000	0	0
SUMO1/HDAC1	0.031	0.029	-10000	0	-0.26	1	1
HDAC complex	0.055	0.015	-10000	0	-10000	0	0
GATA1/Fog1	-0.008	0.12	-10000	0	-0.39	45	45
FKBP25/HDAC1/HDAC2	0.043	0.013	-10000	0	-10000	0	0
TNF	0.012	0.079	0.23	1	-0.53	10	11
negative regulation of cell growth	0.01	0.058	-10000	0	-0.34	4	4
NuRD/MBD2/PRMT5 Complex	0.024	0.036	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.03	0.028	-10000	0	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.005	0.064	-10000	0	-0.33	12	12
SIN3/HDAC complex/NCoR1	0	0.077	-10000	0	-0.31	21	21
TFCP2	0.023	0.002	-10000	0	-10000	0	0
NR2C1	0.023	0.002	-10000	0	-10000	0	0
MBD3	0.021	0.025	-10000	0	-0.53	1	1
MBD2	0.022	0.005	-10000	0	-10000	0	0

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.002	0.045	-10000	0	-10000	0	0
PLK1	0.061	0.11	-10000	0	-0.97	1	1
CDKN1B	0.07	0.1	0.3	3	-0.36	14	17
FOXO3	0.067	0.1	-10000	0	-0.73	3	3
KAT2B	0.028	0.016	-10000	0	-10000	0	0
FOXO1/SIRT1	0.019	0.036	-10000	0	-10000	0	0
CAT	0.049	0.14	-10000	0	-1.1	3	3
CTNNB1	0.021	0.006	-10000	0	-10000	0	0
AKT1	0.029	0.016	-10000	0	-10000	0	0
FOXO1	0.007	0.043	-10000	0	-10000	0	0
MAPK10	0.018	0.048	0.19	17	-0.28	7	24
mol:GTP	0.001	0	-10000	0	-10000	0	0
FOXO4	0.034	0.06	0.26	8	-10000	0	8
response to oxidative stress	0.01	0.01	-10000	0	-10000	0	0
FOXO3A/SIRT1	0.068	0.099	-10000	0	-0.92	1	1
XPO1	0.021	0.007	-10000	0	-10000	0	0
EP300	0.023	0.004	-10000	0	-10000	0	0
BCL2L11	0.032	0.043	-10000	0	-0.79	1	1
FOXO1/SKP2	0.017	0.039	0.25	2	-10000	0	2
mol:GDP	0.01	0.01	-10000	0	-10000	0	0
RAN	0.023	0.002	-10000	0	-10000	0	0
GADD45A	0.048	0.14	-10000	0	-0.61	17	17
YWHAQ	0.022	0.004	-10000	0	-10000	0	0
FOXO1/14-3-3 family	0.014	0.12	-10000	0	-0.45	21	21
MST1	0.028	0.019	0.24	1	-10000	0	1
CSNK1D	0.022	0.004	-10000	0	-10000	0	0
CSNK1E	0.022	0.004	-10000	0	-10000	0	0
FOXO4/14-3-3 family	0.016	0.087	-10000	0	-0.42	11	11
YWHAB	0.022	0.004	-10000	0	-10000	0	0
MAPK8	0.022	0.031	0.19	16	-10000	0	16
MAPK9	0.022	0.032	0.19	17	-10000	0	17
YWHAG	0.022	0.004	-10000	0	-10000	0	0
YWHAE	0.022	0.005	-10000	0	-10000	0	0
YWHAZ	0.022	0.005	-10000	0	-10000	0	0
SIRT1	0.021	0.012	-10000	0	-10000	0	0
SOD2	0.059	0.097	-10000	0	-0.62	2	2
RBL2	0.035	0.2	-10000	0	-0.81	23	23
RAL/GDP	0.037	0.013	-10000	0	-10000	0	0
CHUK	0.028	0.016	-10000	0	-10000	0	0
Ran/GTP	0.019	0.002	-10000	0	-10000	0	0
CSNK1G2	0.022	0.004	-10000	0	-10000	0	0
RAL/GTP	0.039	0.011	-10000	0	-10000	0	0
CSNK1G1	0.023	0.002	-10000	0	-10000	0	0
FASLG	-0.021	0.28	-10000	0	-1.3	21	21
SKP2	0.02	0.026	0.33	3	-10000	0	3
USP7	0.023	0.005	-10000	0	-10000	0	0
IKBKB	0.028	0.023	0.38	1	-10000	0	1
CCNB1	0.059	0.1	-10000	0	-0.96	1	1
FOXO1-3a-4/beta catenin	0.069	0.087	0.32	2	-0.39	1	3
proteasomal ubiquitin-dependent protein catabolic process	0.017	0.039	0.25	2	-10000	0	2
CSNK1A1	0.021	0.006	-10000	0	-10000	0	0
SGK1	0.029	0.015	-10000	0	-10000	0	0
CSNK1G3	0.021	0.006	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.031	0.01	-10000	0	-10000	0	0
ZFAND5	0.03	0.065	0.36	3	-10000	0	3
SFN	0.039	0.069	0.23	46	-0.38	3	49
CDK2	0.023	0.003	-10000	0	-10000	0	0
FOXO3A/14-3-3	0.025	0.088	-10000	0	-0.41	12	12
CREBBP	0.022	0.005	-10000	0	-10000	0	0
FBXO32	0.062	0.12	-10000	0	-0.98	1	1
BCL6	0.051	0.095	-10000	0	-0.69	1	1
RALB	0.023	0.003	-10000	0	-10000	0	0
RALA	0.022	0.005	-10000	0	-10000	0	0
YWHAH	0.022	0.004	-10000	0	-10000	0	0

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.024	0.008	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP1	0.008	0.003	-10000	0	-10000	0	0
mol:DAG	-0.01	0.023	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	0.021	0.007	-10000	0	-10000	0	0
CaM/Ca2+	0.019	0.023	-10000	0	-10000	0	0
HIF1A	0.025	0.005	-10000	0	-10000	0	0
GAB1	0.021	0.006	-10000	0	-10000	0	0
AKT1	0.052	0.078	0.31	3	-10000	0	3
PLCG1	-0.01	0.023	-10000	0	-10000	0	0
NOS3	0.033	0.052	0.31	1	-10000	0	1
CBL	0.022	0.004	-10000	0	-10000	0	0
mol:NO	0.038	0.075	0.42	6	-0.4	2	8
FLT1	0.011	0.003	-10000	0	-10000	0	0
PGF	0.033	0.049	0.24	27	-10000	0	27
VEGFR1 homodimer/NRP2/VEGFR121	0.033	0.029	-10000	0	-0.31	2	2
CALM1	0.022	0.005	-10000	0	-10000	0	0
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
eNOS/Hsp90	0.042	0.072	0.3	1	-0.38	3	4
endothelial cell proliferation	0.008	0.053	-10000	0	-10000	0	0
mol:Ca2+	-0.01	0.023	-10000	0	-10000	0	0
MAPK3	-0.011	0.038	0.34	3	-10000	0	3
MAPK1	-0.01	0.041	0.34	4	-10000	0	4
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
PLGF homodimer	0.033	0.049	0.24	27	-10000	0	27
PRKACA	0.022	0.004	-10000	0	-10000	0	0
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	-0.12	0.24	-10000	0	-0.53	127	127
VEGFA homodimer	0.022	0.004	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0.023	0.008	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	-0.012	0.042	0.32	5	-10000	0	5
PI3K	0.028	0.035	-10000	0	-10000	0	0
PRKCA	-0.012	0.024	-10000	0	-10000	0	0
PRKCB	-0.023	0.059	-10000	0	-10000	0	0
VEGFR1 homodimer/PLGF homodimer	0.03	0.033	-10000	0	-10000	0	0
VEGFA	0.022	0.004	-10000	0	-10000	0	0
VEGFB	0.023	0.002	-10000	0	-10000	0	0
mol:IP3	-0.01	0.023	-10000	0	-10000	0	0
RASA1	-0.008	0.02	-10000	0	-10000	0	0
NRP2	0.019	0.043	-10000	0	-0.53	3	3
VEGFR1 homodimer	0.011	0.003	-10000	0	-10000	0	0
VEGFB homodimer	0.023	0.002	-10000	0	-10000	0	0
NCK1	0.019	0.008	-10000	0	-10000	0	0
eNOS/Caveolin-1	-0.023	0.14	0.43	5	-0.45	10	15
PTPN11	0.023	0.002	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.027	0.033	-10000	0	-10000	0	0
mol:L-citrulline	0.038	0.075	0.42	6	-0.4	2	8
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.046	0.017	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.03	0.017	-10000	0	-10000	0	0
CD2AP	0.022	0.004	-10000	0	-10000	0	0
PI3K/GAB1	0.035	0.04	-10000	0	-10000	0	0
PDPK1	0.054	0.087	0.34	2	-10000	0	2
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.035	0.012	-10000	0	-10000	0	0
mol:NADP	0.038	0.075	0.42	6	-0.4	2	8
HSP90AA1	0.022	0.005	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.044	0.017	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP2	0.022	0.028	-10000	0	-0.32	3	3

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.016	0.017	-10000	0	-10000	0	0
regulation of axonogenesis	-0.005	0.021	0.24	2	-0.17	3	5
myoblast fusion	-0.026	0.037	0.34	1	-10000	0	1
mol:GTP	0.016	0.027	-10000	0	-0.15	10	10
regulation of calcium-dependent cell-cell adhesion	-0.044	0.028	-10000	0	-10000	0	0
ARF1/GTP	0.027	0.027	-10000	0	-10000	0	0
mol:GM1	0.007	0.02	-10000	0	-10000	0	0
mol:Choline	0.004	0.019	0.23	3	-10000	0	3
lamellipodium assembly	0.009	0.043	-10000	0	-0.33	6	6
MAPK3	0.017	0.017	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.045	0.029	-10000	0	-10000	0	0
ARF1	0.022	0.004	-10000	0	-10000	0	0
ARF6/GDP	0.026	0.037	-10000	0	-0.34	1	1
ARF1/GDP	0.025	0.047	-10000	0	-0.21	11	11
ARF6	0.029	0.012	-10000	0	-10000	0	0
RAB11A	0.023	0.002	-10000	0	-10000	0	0
TIAM1	0.022	0.024	-10000	0	-0.49	1	1
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.017	0.017	-10000	0	-10000	0	0
actin filament bundle formation	-0.024	0.043	0.25	3	-10000	0	3
KALRN	0.006	0.034	-10000	0	-0.29	6	6
RAB11FIP3/RAB11A	0.033	0.006	-10000	0	-10000	0	0
RhoA/GDP	0.024	0.044	-10000	0	-0.25	3	3
NME1	0.023	0.012	0.24	1	-10000	0	1
Rac1/GDP	0.025	0.045	-10000	0	-0.24	4	4
substrate adhesion-dependent cell spreading	0.016	0.027	-10000	0	-0.15	10	10
cortical actin cytoskeleton organization	0.009	0.044	-10000	0	-0.33	6	6
RAC1	0.022	0.004	-10000	0	-10000	0	0
liver development	0.016	0.027	-10000	0	-0.15	10	10
ARF6/GTP	0.016	0.027	-10000	0	-0.15	10	10
RhoA/GTP	0.026	0.025	-10000	0	-10000	0	0
mol:GDP	0.007	0.028	-10000	0	-0.21	7	7
ARF6/GTP/RAB11FIP3/RAB11A	0.04	0.027	-10000	0	-10000	0	0
RHOA	0.021	0.007	-10000	0	-10000	0	0
PLD1	0.009	0.027	0.28	3	-10000	0	3
RAB11FIP3	0.022	0.004	-10000	0	-10000	0	0
tube morphogenesis	0.009	0.043	-10000	0	-0.33	6	6
ruffle organization	0.005	0.021	0.17	3	-0.24	2	5
regulation of epithelial cell migration	0.016	0.027	-10000	0	-0.15	10	10
PLD2	0.015	0.018	-10000	0	-10000	0	0
PIP5K1A	0.005	0.021	0.17	3	-0.24	2	5
mol:Phosphatidic acid	0.004	0.019	0.23	3	-10000	0	3
Rac1/GTP	0.009	0.044	-10000	0	-0.34	6	6

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	0.041	0.11	-10000	0	-0.4	11	11
CaM/Ca2+	0.016	0.004	-10000	0	-10000	0	0
AKT1	0.022	0.005	-10000	0	-10000	0	0
AKT2	0.021	0.007	-10000	0	-10000	0	0
STXBP4	0.022	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.028	0.12	0.44	1	-0.41	15	16
YWHAZ	0.022	0.005	-10000	0	-10000	0	0
CALM1	0.022	0.005	-10000	0	-10000	0	0
YWHAQ	0.022	0.004	-10000	0	-10000	0	0
TBC1D4	-0.009	0.003	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.022	0.004	-10000	0	-10000	0	0
YWHAB	0.022	0.004	-10000	0	-10000	0	0
SNARE/Synip	0.042	0.013	-10000	0	-10000	0	0
YWHAG	0.022	0.004	-10000	0	-10000	0	0
ASIP	0.008	0.027	0.3	2	-10000	0	2
PRKCI	0.013	0.011	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0.016	0.004	-10000	0	-10000	0	0
RHOQ	0.022	0.005	-10000	0	-10000	0	0
GYS1	0.005	0.003	-10000	0	-10000	0	0
PRKCZ	0.022	0.005	-10000	0	-10000	0	0
TRIP10	0.022	0.004	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.028	0.009	-10000	0	-10000	0	0
AS160/14-3-3	0.019	0.039	-10000	0	-0.3	2	2
VAMP2	0.021	0.005	-10000	0	-10000	0	0
SLC2A4	0.027	0.12	0.45	1	-0.46	15	16
STX4	0.022	0.003	-10000	0	-10000	0	0
GSK3B	0.013	0.007	-10000	0	-10000	0	0
SFN	0.039	0.069	0.23	46	-0.38	3	49
LNPEP	0.021	0.006	-10000	0	-10000	0	0
YWHAE	0.022	0.005	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.009	0.003	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.031	0.014	-10000	0	-10000	0	0
CDKN1B	0.019	0.064	-10000	0	-0.38	7	7
CDKN1A	0.015	0.048	-10000	0	-0.34	6	6
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.022	0.005	-10000	0	-10000	0	0
FOXO3	0.014	0.056	-10000	0	-0.38	7	7
AKT1	0.005	0.051	-10000	0	-0.4	7	7
BAD	0.023	0.002	-10000	0	-10000	0	0
AKT3	0.008	0.027	-10000	0	-0.34	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.013	0.056	-10000	0	-0.37	8	8
AKT1/ASK1	0.031	0.063	-10000	0	-0.36	8	8
BAD/YWHAZ	0.042	0.013	-10000	0	-10000	0	0
RICTOR	0.018	0.009	-10000	0	-10000	0	0
RAF1	0.021	0.006	-10000	0	-10000	0	0
JNK cascade	-0.03	0.061	0.35	8	-10000	0	8
TSC1	0.012	0.056	-10000	0	-0.37	8	8
YWHAZ	0.022	0.005	-10000	0	-10000	0	0
AKT1/RAF1	0.034	0.066	-10000	0	-0.38	6	6
EP300	0.022	0.004	-10000	0	-10000	0	0
mol:GDP	0.006	0.054	-10000	0	-0.38	8	8
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.016	0.035	-10000	0	-0.29	4	4
YWHAQ	0.022	0.004	-10000	0	-10000	0	0
TBC1D4	0.003	0.001	-10000	0	-10000	0	0
MAP3K5	0.022	0.003	-10000	0	-10000	0	0
MAPKAP1	0.022	0.003	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.024	0.066	0.37	6	-0.29	1	7
YWHAH	0.022	0.004	-10000	0	-10000	0	0
AKT1S1	0.015	0.045	-10000	0	-0.35	5	5
CASP9	0.014	0.044	-10000	0	-0.35	5	5
YWHAB	0.022	0.004	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.036	0.071	0.3	1	-0.38	6	7
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.042	0.014	-10000	0	-10000	0	0
YWHAE	0.022	0.005	-10000	0	-10000	0	0
SRC	0.022	0.004	-10000	0	-10000	0	0
AKT2/p21CIP1	0.012	0.054	0.25	1	-0.42	4	5
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.009	0.052	-10000	0	-0.34	9	9
CHUK	0.015	0.042	-10000	0	-0.37	4	4
BAD/BCL-XL	0.033	0.063	-10000	0	-0.58	2	2
mTORC2	0.023	0.012	-10000	0	-10000	0	0
AKT2	0.01	0.004	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.03	0.086	0.3	1	-0.49	6	7
PDPK1	0.022	0.004	-10000	0	-10000	0	0
MDM2	0.016	0.062	-10000	0	-0.37	8	8
MAPKKK cascade	-0.033	0.064	0.34	8	-10000	0	8
MDM2/Cbp/p300	0.047	0.073	0.3	1	-0.46	3	4
TSC1/TSC2	0.011	0.052	0.23	2	-0.38	6	8
proteasomal ubiquitin-dependent protein catabolic process	0.045	0.07	0.29	1	-0.43	3	4
glucose import	-0.004	0.026	0.2	2	-0.29	3	5
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.015	0.049	0.3	1	-0.35	4	5
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.005	0.023	-10000	0	-0.3	3	3
GSK3A	0.016	0.047	-10000	0	-0.35	5	5
FOXO1	0.014	0.049	-10000	0	-0.45	4	4
GSK3B	0.024	0.071	-10000	0	-0.38	7	7
SFN	0.039	0.069	0.23	46	-0.38	3	49
G1/S transition of mitotic cell cycle	0.035	0.076	0.27	17	-0.39	3	20
p27Kip1/14-3-3 family	0.028	0.054	-10000	0	-0.54	2	2
PRKACA	0.022	0.004	-10000	0	-10000	0	0
KPNA1	0.02	0.007	-10000	0	-10000	0	0
HSP90AA1	0.022	0.005	-10000	0	-10000	0	0
YWHAG	0.022	0.004	-10000	0	-10000	0	0
RHEB	0.022	0.004	-10000	0	-10000	0	0
CREBBP	0.022	0.005	-10000	0	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.013	0.035	-10000	0	-0.36	4	4
CRKL	0.021	0.006	-10000	0	-10000	0	0
Rac1/GDP	0.016	0.003	-10000	0	-10000	0	0
DOCK1	0.022	0.004	-10000	0	-10000	0	0
ITGA4	0.016	0.061	-10000	0	-0.53	6	6
alpha4/beta7 Integrin/MAdCAM1	0.047	0.047	-10000	0	-0.3	7	7
EPO	0.017	0.028	0.23	6	-10000	0	6
alpha4/beta7 Integrin	0.027	0.05	-10000	0	-0.39	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.021	0.005	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.027	0.047	-10000	0	-0.39	6	6
EPO/EPOR (dimer)	0.032	0.019	-10000	0	-10000	0	0
lamellipodium assembly	0.042	0.11	-10000	0	-0.53	12	12
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
PI3K	0.017	0.017	-10000	0	-10000	0	0
ARF6	0.022	0.005	-10000	0	-10000	0	0
JAK2	0.014	0.033	-10000	0	-0.34	4	4
PXN	0.023	0.002	-10000	0	-10000	0	0
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
MADCAM1	0.02	0.023	0.23	4	-10000	0	4
cell adhesion	0.045	0.046	-10000	0	-0.3	7	7
CRKL/CBL	0.031	0.01	-10000	0	-10000	0	0
ITGB1	0.022	0.004	-10000	0	-10000	0	0
SRC	-0.012	0.053	0.18	16	-0.36	6	22
ITGB7	0.021	0.025	-10000	0	-0.53	1	1
RAC1	0.022	0.004	-10000	0	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.036	0.061	-10000	0	-0.4	8	8
p130Cas/Crk/Dock1	0.023	0.049	-10000	0	-0.43	2	2
VCAM1	0.019	0.053	0.23	4	-0.53	4	8
RHOA	0.021	0.007	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.05	0.039	-10000	0	-0.3	5	5
BCAR1	-0.013	0.051	-10000	0	-0.34	6	6
EPOR	0.022	0.004	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.022	0.004	-10000	0	-10000	0	0
GIT1	0.022	0.003	-10000	0	-10000	0	0
Rac1/GTP	0.042	0.12	-10000	0	-0.56	12	12

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.021	0.006	-10000	0	-10000	0	0
Rac1/GDP	0.022	0.01	-10000	0	-10000	0	0
DOCK1	0.022	0.004	-10000	0	-10000	0	0
ITGA4	0.016	0.061	-10000	0	-0.53	6	6
RAC1	0.022	0.004	-10000	0	-10000	0	0
alpha4/beta7 Integrin	0.027	0.05	-10000	0	-0.39	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.021	0.005	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.039	0.038	-10000	0	-0.34	4	4
alpha4/beta7 Integrin/Paxillin	0.03	0.036	-10000	0	-0.31	5	5
lamellipodium assembly	-0.014	0.1	-10000	0	-0.4	25	25
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
PI3K	0.017	0.017	-10000	0	-10000	0	0
ARF6	0.022	0.005	-10000	0	-10000	0	0
TLN1	0.021	0.007	-10000	0	-10000	0	0
PXN	-0.01	0.002	-10000	0	-10000	0	0
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
ARF6/GTP	0.039	0.033	-10000	0	-0.27	4	4
cell adhesion	0.037	0.033	-10000	0	-0.29	3	3
CRKL/CBL	0.031	0.01	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.031	0.033	-10000	0	-0.31	4	4
ITGB1	0.022	0.004	-10000	0	-10000	0	0
ITGB7	0.021	0.025	-10000	0	-0.53	1	1
ARF6/GDP	0.022	0.01	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.04	0.051	-10000	0	-0.34	7	7
p130Cas/Crk/Dock1	0.041	0.015	-10000	0	-10000	0	0
VCAM1	0.019	0.053	0.23	4	-0.53	4	8
alpha4/beta1 Integrin/Paxillin/Talin	0.039	0.033	-10000	0	-0.29	3	3
alpha4/beta1 Integrin/Paxillin/GIT1	0.041	0.035	-10000	0	-0.29	4	4
BCAR1	0.022	0.005	-10000	0	-10000	0	0
mol:GDP	-0.04	0.034	0.29	4	-10000	0	4
CBL	0.022	0.004	-10000	0	-10000	0	0
PRKACA	0.022	0.004	-10000	0	-10000	0	0
GIT1	0.022	0.003	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.039	0.033	-10000	0	-0.29	3	3
Rac1/GTP	-0.016	0.11	-10000	0	-0.45	25	25

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.009	0.09	-10000	0	-0.34	23	23
KLHL20	0.017	0.058	0.17	1	-0.25	8	9
CYFIP2	0.007	0.089	-10000	0	-0.53	13	13
Rac1/GDP	0.013	0.069	0.25	2	-10000	0	2
ENAH	-0.009	0.094	-10000	0	-0.35	18	18
AP1M1	0.022	0.004	-10000	0	-10000	0	0
RAP1B	0.022	0.005	-10000	0	-10000	0	0
RAP1A	0.022	0.005	-10000	0	-10000	0	0
CTNNB1	0.021	0.006	-10000	0	-10000	0	0
CDC42/GTP	0.014	0.028	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.01	0.035	-10000	0	-0.19	9	9
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.051	0.025	-10000	0	-0.31	1	1
RAPGEF1	-0.004	0.08	-10000	0	-10000	0	0
CTNND1	0.023	0.001	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.005	0.098	-10000	0	-0.34	29	29
CRK	-0.004	0.072	-10000	0	-0.33	6	6
E-cadherin/gamma catenin/alpha catenin	0.042	0.013	-10000	0	-10000	0	0
alphaE/beta7 Integrin	0.031	0.021	-10000	0	-0.39	1	1
IQGAP1	0.022	0.004	-10000	0	-10000	0	0
NCKAP1	0.022	0.004	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.04	0.013	-10000	0	-10000	0	0
DLG1	-0.001	0.064	-10000	0	-0.35	8	8
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.008	0.011	-10000	0	-10000	0	0
MLLT4	0.022	0.004	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.04	0.014	-10000	0	-10000	0	0
PI3K	-0.009	0.014	-10000	0	-10000	0	0
ARF6	0.022	0.005	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
E-cadherin/gamma catenin	0.032	0.008	-10000	0	-10000	0	0
TIAM1	0.021	0.025	-10000	0	-0.53	1	1
E-cadherin(dimer)/Ca2+	0.049	0.017	-10000	0	-10000	0	0
AKT1	0.004	0.03	0.12	2	-10000	0	2
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
CDH1	0.022	0.005	-10000	0	-10000	0	0
RhoA/GDP	0.017	0.065	0.25	2	-10000	0	2
actin cytoskeleton organization	0.015	0.045	0.15	5	-0.18	7	12
CDC42/GDP	0.016	0.068	0.25	2	-10000	0	2
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.014	0.005	-10000	0	-10000	0	0
ITGB7	0.021	0.025	-10000	0	-0.53	1	1
RAC1	0.022	0.004	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.053	0.019	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin	0.037	0.013	-10000	0	-10000	0	0
mol:GDP	0.002	0.074	0.26	2	-0.31	1	3
CDC42/GTP/IQGAP1	0.029	0.007	-10000	0	-10000	0	0
JUP	0.022	0.003	-10000	0	-10000	0	0
p120 catenin/RhoA/GDP	0.023	0.064	0.27	1	-10000	0	1
RAC1/GTP/IQGAP1	0.029	0.007	-10000	0	-10000	0	0
PIP5K1C/AP1M1	0.032	0.008	-10000	0	-10000	0	0
RHOA	0.021	0.007	-10000	0	-10000	0	0
CDC42	0.022	0.004	-10000	0	-10000	0	0
CTNNA1	0.021	0.006	-10000	0	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.009	0.039	0.14	5	-0.23	6	11
NME1	0.023	0.01	0.23	1	-10000	0	1
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	-0.006	0.09	-10000	0	-0.35	16	16
regulation of cell-cell adhesion	0.009	0.024	-10000	0	-10000	0	0
WASF2	0.008	0.025	-10000	0	-10000	0	0
Rap1/GTP	0.018	0.04	-10000	0	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.059	0.027	-10000	0	-0.29	1	1
CCND1	0.011	0.048	0.16	5	-0.3	6	11
VAV2	-0.01	0.12	-10000	0	-0.64	9	9
RAP1/GDP	0.02	0.054	0.25	1	-10000	0	1
adherens junction assembly	-0.006	0.088	-10000	0	-0.34	16	16
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.022	0.004	-10000	0	-10000	0	0
PIP5K1C	0.022	0.004	-10000	0	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.045	0.026	-10000	0	-0.28	1	1
E-cadherin/beta catenin	0.009	0.007	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	-0.008	0.092	-10000	0	-0.35	15	15
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
Rac1/GTP	-0.012	0.076	-10000	0	-0.42	9	9
E-cadherin/beta catenin/alpha catenin	0.042	0.014	-10000	0	-10000	0	0
ITGAE	0.022	0.005	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.006	0.099	-10000	0	-0.35	29	29

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	0.051	0.1	0.37	1	-0.55	3	4
RAD9A	0.022	0.004	-10000	0	-10000	0	0
AP1	-0.016	0.14	-10000	0	-0.39	58	58
IFNAR2	0.025	0.007	-10000	0	-10000	0	0
AKT1	0.008	0.052	-10000	0	-0.23	17	17
ER alpha/Oestrogen	-0.001	0.085	-10000	0	-0.38	24	24
NFX1/SIN3/HDAC complex	0.012	0.058	-10000	0	-0.3	10	10
EGF	0.016	0.068	0.23	3	-0.53	7	10
SMG5	0.022	0.005	-10000	0	-10000	0	0
SMG6	0.022	0.005	-10000	0	-10000	0	0
SP3/HDAC2	0.037	0.011	-10000	0	-10000	0	0
TERT/c-Abl	0.056	0.1	-10000	0	-0.51	3	3
SAP18	0.022	0.006	-10000	0	-10000	0	0
MRN complex	0.041	0.015	-10000	0	-10000	0	0
WT1	0.036	0.051	0.24	27	-10000	0	27
WRN	0.021	0.007	-10000	0	-10000	0	0
SP1	0.026	0.007	-10000	0	-10000	0	0
SP3	0.023	0.006	-10000	0	-10000	0	0
TERF2IP	0.022	0.005	-10000	0	-10000	0	0
Telomerase/Nucleolin	0.059	0.093	-10000	0	-0.47	3	3
Mad/Max	0.034	0.012	-10000	0	-10000	0	0
TERT	0.051	0.11	-10000	0	-0.56	3	3
CCND1	0.062	0.17	0.54	1	-1.1	6	7
MAX	0.023	0.006	-10000	0	-10000	0	0
RBBP7	0.022	0.005	-10000	0	-10000	0	0
RBBP4	0.023	0.004	-10000	0	-10000	0	0
TERF2	0.019	0.008	-10000	0	-10000	0	0
PTGES3	0.023	0.002	-10000	0	-10000	0	0
SIN3A	0.023	0.002	-10000	0	-10000	0	0
Telomerase/911	0.044	0.072	-10000	0	-0.5	3	3
CDKN1B	0.011	0.031	-10000	0	-0.33	4	4
RAD1	0.018	0.009	-10000	0	-10000	0	0
XRCC5	0.022	0.004	-10000	0	-10000	0	0
XRCC6	0.022	0.004	-10000	0	-10000	0	0
SAP30	0.022	0.006	-10000	0	-10000	0	0
TRF2/PARP2	0.03	0.011	-10000	0	-10000	0	0
UBE3A	0.023	0.004	-10000	0	-10000	0	0
JUN	0.023	0.006	-10000	0	-10000	0	0
E6	0.001	0.001	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.019	0.005	-10000	0	-10000	0	0
FOS	-0.042	0.18	-10000	0	-0.53	58	58
IFN-gamma/IRF1	0.034	0.041	-10000	0	-0.38	4	4
PARP2	0.021	0.005	-10000	0	-10000	0	0
BLM	0.027	0.034	0.26	10	-10000	0	10
Telomerase	0.023	0.056	-10000	0	-0.28	2	2
IRF1	0.025	0.007	-10000	0	-10000	0	0
ESR1	-0.003	0.12	-10000	0	-0.53	23	23
KU/TER	0.032	0.008	-10000	0	-10000	0	0
ATM/TRF2	0.032	0.009	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.018	0.055	-10000	0	-0.3	4	4
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.018	0.056	-10000	0	-0.3	4	4
HDAC1	0.023	0.004	-10000	0	-10000	0	0
HDAC2	0.026	0.007	-10000	0	-10000	0	0
ATM	0.011	0.012	-10000	0	-10000	0	0
SMAD3	-0.011	0.004	-10000	0	-10000	0	0
ABL1	0.022	0.003	-10000	0	-10000	0	0
MXD1	0.023	0.006	-10000	0	-10000	0	0
MRE11A	0.022	0.004	-10000	0	-10000	0	0
HUS1	0.022	0.005	-10000	0	-10000	0	0
RPS6KB1	0.022	0.003	-10000	0	-10000	0	0
TERT/NF kappa B1/14-3-3	0.06	0.12	-10000	0	-0.59	4	4
NR2F2	0.019	0.006	-10000	0	-10000	0	0
MAPK3	-0.002	0.013	-10000	0	-10000	0	0
MAPK1	-0.002	0.012	-10000	0	-10000	0	0
TGFB1/TGF beta receptor Type II	0.021	0.005	-10000	0	-10000	0	0
NFKB1	0.022	0.005	-10000	0	-10000	0	0
HNRNPC	0.022	0.005	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.011	0.012	-10000	0	-10000	0	0
NBN	0.022	0.005	-10000	0	-10000	0	0
EGFR	0.023	0.081	0.37	12	-0.53	6	18
mol:Oestrogen	0.001	0.001	-10000	0	-10000	0	0
EGF/EGFR	0.026	0.078	0.27	8	-0.42	12	20
MYC	0.022	0.008	-10000	0	-10000	0	0
IL2	0.022	0.009	-10000	0	-10000	0	0
KU	0.032	0.008	-10000	0	-10000	0	0
RAD50	0.021	0.006	-10000	0	-10000	0	0
HSP90AA1	0.022	0.005	-10000	0	-10000	0	0
TGFB1	0.021	0.005	-10000	0	-10000	0	0
TRF2/BLM	0.034	0.023	0.25	2	-10000	0	2
FRAP1	0	0	-10000	0	-10000	0	0
KU/TERT	0.065	0.1	-10000	0	-0.51	3	3
SP1/HDAC2	0.041	0.012	-10000	0	-10000	0	0
PINX1	0.02	0.007	-10000	0	-10000	0	0
Telomerase/EST1A	0.059	0.092	-10000	0	-0.47	3	3
Smad3/Myc	0.019	0.008	-10000	0	-10000	0	0
911 complex	0.035	0.02	-10000	0	-10000	0	0
IFNG	0.021	0.051	0.24	2	-0.53	4	6
Telomerase/PinX1	0.054	0.092	-10000	0	-0.47	3	3
Telomerase/AKT1/mTOR/p70S6K	0.021	0.093	-10000	0	-0.51	10	10
SIN3B	0.022	0.005	-10000	0	-10000	0	0
YWHAE	0.022	0.005	-10000	0	-10000	0	0
Telomerase/EST1B	0.058	0.091	-10000	0	-0.5	2	2
response to DNA damage stimulus	0.003	0.016	-10000	0	-10000	0	0
MRN complex/TRF2/Rap1	0.056	0.023	-10000	0	-10000	0	0
TRF2/WRN	0.029	0.014	-10000	0	-10000	0	0
Telomerase/hnRNP C1/C2	0.057	0.093	-10000	0	-0.47	3	3
E2F1	0.024	0.008	-10000	0	-10000	0	0
ZNFX1	0.023	0.004	-10000	0	-10000	0	0
PIF1	0.044	0.063	0.23	51	-10000	0	51
NCL	0.022	0.004	-10000	0	-10000	0	0
DKC1	0.022	0.004	-10000	0	-10000	0	0
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

p38 MAPK 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.017	0.01	-10000	0	-10000	0	0
TRAF2/ASK1	0.03	0.007	-10000	0	-10000	0	0
ATM	0.022	0.004	-10000	0	-10000	0	0
MAP2K3	0	0.093	0.3	1	-0.37	16	17
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.001	0.077	0.31	1	-0.35	12	13
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.018	0.05	-10000	0	-0.53	4	4
TXN	0.005	0.001	-10000	0	-10000	0	0
CALM1	0.022	0.005	-10000	0	-10000	0	0
GADD45A	0.022	0.004	-10000	0	-10000	0	0
GADD45B	0.009	0.085	-10000	0	-0.53	12	12
MAP3K1	0.021	0.006	-10000	0	-10000	0	0
MAP3K6	0.022	0.004	-10000	0	-10000	0	0
MAP3K7	0.023	0.002	-10000	0	-10000	0	0
MAP3K4	0.022	0.003	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.032	0.008	-10000	0	-10000	0	0
TAK1/TAB family	-0.002	0.018	-10000	0	-0.14	5	5
RAC1/OSM/MEKK3	0.041	0.011	-10000	0	-10000	0	0
TRAF2	0.022	0.004	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.017	0.079	-10000	0	-0.35	7	7
TRAF6	0.005	0.001	-10000	0	-10000	0	0
RAC1	0.022	0.004	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	0.047	0.073	0.24	58	-0.3	1	59
CCM2	0.022	0.005	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	0.043	0.045	0.24	4	-0.17	1	5
MAPK11	0.022	0.005	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.054	0.045	0.24	4	-10000	0	4
OSM/MEKK3	0.032	0.008	-10000	0	-10000	0	0
TAOK1	0.01	0.01	-10000	0	-0.21	1	1
TAOK2	0.01	0.002	-10000	0	-10000	0	0
TAOK3	0.011	0.002	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.022	0.004	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.022	0.003	-10000	0	-10000	0	0
MAP3K10	0.021	0.017	0.38	1	-10000	0	1
MAP3K3	0.022	0.003	-10000	0	-10000	0	0
TRX/ASK1	0.019	0.013	-10000	0	-10000	0	0
GADD45/MTK1/MTK1	0.039	0.064	-10000	0	-0.31	15	15

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.022	0.007	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.032	0.088	-10000	0	-0.36	9	9
ERC1	0.021	0.006	-10000	0	-10000	0	0
RIP2/NOD2	0.03	0.021	-10000	0	-0.39	1	1
NFKBIA	-0.006	0.02	-10000	0	-10000	0	0
BIRC2	0.022	0.004	-10000	0	-10000	0	0
IKBKB	0.021	0.017	0.38	1	-10000	0	1
RIPK2	0.022	0.005	-10000	0	-10000	0	0
IKBKG	0.016	0.025	-10000	0	-10000	0	0
IKK complex/A20	0.024	0.1	-10000	0	-0.44	9	9
NEMO/A20/RIP2	0.022	0.005	-10000	0	-10000	0	0
XPO1	0.021	0.007	-10000	0	-10000	0	0
NEMO/ATM	0.014	0.097	-10000	0	-0.43	13	13
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.023	0.002	-10000	0	-10000	0	0
Exportin 1/RanGTP	0.028	0.009	-10000	0	-10000	0	0
IKK complex/ELKS	0.019	0.087	-10000	0	-0.42	9	9
BCL10/MALT1/TRAF6	0.042	0.013	-10000	0	-10000	0	0
NOD2	0.02	0.025	-10000	0	-0.53	1	1
NFKB1	0.023	0.005	-10000	0	-10000	0	0
RELA	0.024	0.002	-10000	0	-10000	0	0
MALT1	0.022	0.005	-10000	0	-10000	0	0
cIAP1/UbcH5C	0.031	0.009	-10000	0	-10000	0	0
ATM	0.022	0.004	-10000	0	-10000	0	0
TNF/TNFR1A	0.023	0.056	-10000	0	-0.39	8	8
TRAF6	0.022	0.004	-10000	0	-10000	0	0
PRKCA	0.02	0.035	-10000	0	-0.53	2	2
CHUK	0.022	0.005	-10000	0	-10000	0	0
UBE2D3	0.022	0.005	-10000	0	-10000	0	0
TNF	0.012	0.079	0.23	1	-0.53	10	11
NF kappa B1 p50/RelA	0.046	0.016	-10000	0	-10000	0	0
BCL10	0.022	0.004	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.006	0.02	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.022	0.007	-10000	0	-10000	0	0
TNFRSF1A	0.021	0.006	-10000	0	-10000	0	0
IKK complex	0.024	0.095	-10000	0	-0.44	10	10
CYLD	0.022	0.005	-10000	0	-10000	0	0
IKK complex/PKC alpha	0.031	0.099	-10000	0	-0.47	10	10

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	-0.011	0.004	-10000	0	-10000	0	0
SNTA1	0.022	0.005	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	-0.011	0.004	-10000	0	-10000	0	0
MAPK12	-0.005	0.002	-10000	0	-10000	0	0
CCND1	0.001	0.043	-10000	0	-0.42	5	5
p38 gamma/SNTA1	0.016	0.034	0.19	13	-10000	0	13
MAP2K3	0.022	0.005	-10000	0	-10000	0	0
PKN1	0.022	0.004	-10000	0	-10000	0	0
G2/M transition checkpoint	-0.005	0.002	-10000	0	-10000	0	0
MAP2K6	-0.002	0.002	-10000	0	-10000	0	0
MAPT	0.002	0.052	0.2	4	-0.3	8	12
MAPK13	-0.01	0.003	-10000	0	-10000	0	0
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.005	0.001	-10000	0	-10000	0	0

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	0.018	0.043	-10000	0	-0.53	3	3
CLTC	0.019	0.069	-10000	0	-0.38	12	12
calcium ion-dependent exocytosis	0.006	0.024	-10000	0	-0.24	2	2
Dynamin 2/GTP	0.02	0.007	-10000	0	-10000	0	0
EXOC4	0.022	0.004	-10000	0	-10000	0	0
CD59	0.004	0.04	-10000	0	-0.34	6	6
CPE	0.009	0.016	-10000	0	-0.33	1	1
CTNNB1	0.021	0.006	-10000	0	-10000	0	0
membrane fusion	0.007	0.015	-10000	0	-10000	0	0
CTNND1	-0.006	0.034	0.18	16	-10000	0	16
DNM2	0.022	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.005	0.043	0.21	4	-0.28	5	9
TSHR	0.011	0.016	-10000	0	-10000	0	0
INS	0.001	0.1	-10000	0	-0.54	17	17
BIN1	0.02	0.035	-10000	0	-0.53	2	2
mol:Choline	0.007	0.015	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.01	0.005	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.022	0.005	-10000	0	-10000	0	0
mol:Ca2+	0.019	0.007	-10000	0	-10000	0	0
JUP	0.003	0.043	-10000	0	-0.34	7	7
ASAP2/amphiphysin II	0.039	0.024	-10000	0	-0.3	2	2
ARF6/GTP	0.016	0.004	-10000	0	-10000	0	0
CDH1	0.005	0.034	-10000	0	-0.35	4	4
clathrin-independent pinocytosis	0.016	0.004	-10000	0	-10000	0	0
MAPK8IP3	0.022	0.004	-10000	0	-10000	0	0
positive regulation of endocytosis	0.016	0.004	-10000	0	-10000	0	0
EXOC2	0.022	0.004	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.006	0.044	-10000	0	-0.32	3	3
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.022	0.003	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.031	0.052	0.32	5	-10000	0	5
positive regulation of phagocytosis	0.01	0.003	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.029	0.008	-10000	0	-10000	0	0
ACAP1	0.009	0.016	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	-0.038	0.094	-10000	0	-0.46	7	7
clathrin heavy chain/ACAP1	0.005	0.054	0.24	3	-0.35	7	10
JIP4/KLC1	0.04	0.013	-10000	0	-10000	0	0
EXOC1	0.021	0.006	-10000	0	-10000	0	0
exocyst	0.01	0.038	-10000	0	-0.32	3	3
RALA/GTP	0.016	0.003	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.029	0.008	-10000	0	-10000	0	0
receptor recycling	0.016	0.004	-10000	0	-10000	0	0
CTNNA1	-0.007	0.032	0.18	14	-10000	0	14
NME1	0.01	0.005	-10000	0	-10000	0	0
clathrin coat assembly	0.021	0.071	0.31	1	-0.37	12	13
IL2RA	0.005	0.037	-10000	0	-0.32	5	5
VAMP3	0.01	0.003	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	0.029	0.063	-10000	0	-0.36	6	6
EXOC6	0.022	0.005	-10000	0	-10000	0	0
PLD1	0.007	0.015	0.18	3	-10000	0	3
PLD2	0.009	0.008	-10000	0	-10000	0	0
EXOC5	0.022	0.004	-10000	0	-10000	0	0
PIP5K1C	0.004	0.038	-10000	0	-0.29	5	5
SDC1	0.003	0.045	-10000	0	-0.34	7	7
ARF6/GDP	0.019	0.006	-10000	0	-10000	0	0
EXOC7	0.022	0.004	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.033	0.054	-10000	0	-0.33	5	5
mol:Phosphatidic acid	0.007	0.015	-10000	0	-10000	0	0
endocytosis	-0.038	0.024	0.3	2	-10000	0	2
SCAMP2	0.023	0.002	-10000	0	-10000	0	0
ADRB2	-0.05	0.13	-10000	0	-0.44	12	12
EXOC3	0.018	0.009	-10000	0	-10000	0	0
ASAP2	0.022	0.004	-10000	0	-10000	0	0
Dynamin 2/GDP	0.023	0.008	-10000	0	-10000	0	0
KLC1	0.022	0.005	-10000	0	-10000	0	0
AVPR2	-0.041	0.13	0.26	1	-0.41	17	18
RALA	0.022	0.004	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.027	0.051	-10000	0	-0.31	4	4

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	-0.019	0.035	0.53	2	-10000	0	2
PI3K Class IB/PDE3B	0.019	0.035	-10000	0	-0.53	2	2
PDE3B	0.019	0.035	-10000	0	-0.53	2	2

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.036	0.023	-10000	0	-10000	0	0
CLOCK	0.022	0.007	-10000	0	-10000	0	0
TIMELESS/CRY2	0.033	0.018	-10000	0	-10000	0	0
DEC1/BMAL1	0.039	0.034	-10000	0	-10000	0	0
ATR	0.018	0.009	-10000	0	-10000	0	0
NR1D1	0.014	0.006	-10000	0	-10000	0	0
ARNTL	0.023	0.005	-10000	0	-10000	0	0
TIMELESS	0.014	0.006	-10000	0	-10000	0	0
NPAS2	0.024	0.003	-10000	0	-10000	0	0
CRY2	0.022	0.004	-10000	0	-10000	0	0
mol:CO	-0.006	0	-10000	0	-10000	0	0
CHEK1	0.023	0.01	0.23	1	-10000	0	1
mol:HEME	0.006	0	-10000	0	-10000	0	0
PER1	0.019	0.035	-10000	0	-0.53	2	2
BMAL/CLOCK/NPAS2	0.047	0.018	-10000	0	-10000	0	0
BMAL1/CLOCK	0.022	0.049	-10000	0	-10000	0	0
S phase of mitotic cell cycle	0.036	0.023	-10000	0	-10000	0	0
TIMELESS/CHEK1/ATR	0.036	0.024	-10000	0	-10000	0	0
mol:NADPH	0.006	0	-10000	0	-10000	0	0
PER1/TIMELESS	0.031	0.025	-10000	0	-10000	0	0
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.015	0.056	0.23	28	-10000	0	28

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	-0.015	0.053	0.24	2	-10000	0	2
GNAI2	0.021	0.007	-10000	0	-10000	0	0
S1P/S1P5/G12	0.03	0.022	-10000	0	-0.33	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.021	0.029	0.23	2	-0.53	1	3
RhoA/GTP	0.016	0.054	-10000	0	-0.24	2	2
negative regulation of cAMP metabolic process	0.017	0.035	-10000	0	-0.22	5	5
GNAZ	0.016	0.056	-10000	0	-0.53	5	5
GNAI3	0.022	0.005	-10000	0	-10000	0	0
GNA12	0.022	0.004	-10000	0	-10000	0	0
S1PR5	0.024	0.035	0.23	7	-0.53	1	8
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	0.017	0.035	-10000	0	-0.22	5	5
RhoA/GDP	0.015	0.005	-10000	0	-10000	0	0
RHOA	0.021	0.007	-10000	0	-10000	0	0
GNAI1	0.021	0.025	-10000	0	-0.53	1	1

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0.031	0.043	-10000	0	-0.33	6	6
MAPK9	0.005	0.002	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.01	0.004	-10000	0	-10000	0	0
GNB1/GNG2	0.024	0.04	-10000	0	-0.33	6	6
GNB1	0.021	0.025	-10000	0	-0.53	1	1
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	0.005	0.001	-10000	0	-10000	0	0
Gs family/GTP	0.013	0.021	-10000	0	-0.23	3	3
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	0.001	0.005	0.062	3	-10000	0	3
GNAL	0.02	0.035	-10000	0	-0.53	2	2
GNG2	0.016	0.055	-10000	0	-0.53	5	5
CRH	-0.01	0.019	0.23	1	-10000	0	1
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.005	0.001	-10000	0	-10000	0	0
MAPK11	0.005	0.001	-10000	0	-10000	0	0

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.004	0.019	-10000	0	-10000	0	0
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.012	0.031	-10000	0	-0.17	3	3
AP2	0.019	0.02	0.27	1	-10000	0	1
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.028	0.012	-10000	0	-10000	0	0
CLTB	0.021	0.006	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.012	0.006	-10000	0	-10000	0	0
CD4	0.006	0.092	-10000	0	-0.53	14	14
CLTA	0.021	0.007	-10000	0	-10000	0	0
mol:GTP	-0.002	0.002	-10000	0	-10000	0	0
ARFGAP1	-0.005	0.001	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.004	0.008	-10000	0	-10000	0	0
ARF1/GTP	0.026	0.011	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.006	0.003	-10000	0	-10000	0	0
mol:Choline	0.004	0.008	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.023	0.007	-10000	0	-10000	0	0
DDEF1	0.003	0.008	-10000	0	-10000	0	0
ARF1/GDP	0.003	0.015	-10000	0	-0.12	1	1
AP2M1	0.013	0.02	0.38	1	-10000	0	1
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	0.009	0.005	-10000	0	-10000	0	0
Rac/GTP	0.017	0.005	-10000	0	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.03	0.011	-10000	0	-10000	0	0
ARFIP2	0.018	0.013	-10000	0	-10000	0	0
COPA	0.022	0.005	-10000	0	-10000	0	0
RAC1	0.022	0.004	-10000	0	-10000	0	0
ARF1/GTP/coatomer protein complex	0.01	0.034	-10000	0	-0.2	6	6
ARF1/GTP/ARHGAP10	0.015	0.006	-10000	0	-10000	0	0
GGA3	0.022	0.004	-10000	0	-10000	0	0
ARF1/GTP/Membrin	0.019	0.017	-10000	0	-0.25	1	1
AP2A1	0.022	0.004	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.001	0.04	-10000	0	-0.21	9	9
ARF1/GDP/Membrin	0.021	0.021	-10000	0	-0.24	2	2
Arfaptin 2/Rac/GDP	0.028	0.009	-10000	0	-10000	0	0
CYTH2	0.024	0.006	-10000	0	-10000	0	0
ARF1/GTP/GGA3	0.029	0.01	-10000	0	-10000	0	0
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.016	0.003	-10000	0	-10000	0	0
mol:Brefeldin A	0	0	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.006	0.029	-10000	0	-0.23	5	5
PLD2	0.004	0.008	-10000	0	-10000	0	0
ARF-GAP1/v-SNARE	-0.005	0.001	-10000	0	-10000	0	0
PIP5K1A	0.004	0.008	-10000	0	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0.014	0.018	-10000	0	-10000	0	0
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.004	0.008	-10000	0	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	-0.005	0.001	-10000	0	-10000	0	0
GOSR2	0.009	0.016	-10000	0	-0.33	1	1
USO1	0.005	0.037	-10000	0	-0.32	6	6
GBF1	0.001	0.052	-10000	0	-0.32	13	13
ARF1/GTP/Arfaptin 2	0.03	0.011	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.018	0.046	0.25	1	-0.34	4	5

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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
SMAD4	0.022	0.005	-10000	0	-10000	0	0
SMAD2	0.003	0.043	0.21	1	-0.23	6	7
SMAD3	0.019	0.028	-10000	0	-10000	0	0
SMAD3/SMAD4	0.024	0.057	-10000	0	-0.46	4	4
SMAD4/Ubc9/PIASy	0.042	0.014	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.04	0.053	-10000	0	-10000	0	0
PPM1A	0.022	0.004	-10000	0	-10000	0	0
CALM1	0.022	0.005	-10000	0	-10000	0	0
SMAD2/SMAD4	0.01	0.05	-10000	0	-0.24	5	5
MAP3K1	0.021	0.006	-10000	0	-10000	0	0
TRAP-1/SMAD4	0.032	0.008	-10000	0	-10000	0	0
MAPK3	0.022	0.003	-10000	0	-10000	0	0
MAPK1	0.021	0.006	-10000	0	-10000	0	0
NUP214	0.022	0.003	-10000	0	-10000	0	0
CTDSP1	0.022	0.004	-10000	0	-10000	0	0
CTDSP2	0.022	0.003	-10000	0	-10000	0	0
CTDSPL	0.021	0.007	-10000	0	-10000	0	0
KPNB1	0.022	0.003	-10000	0	-10000	0	0
TGFBRAP1	0.023	0.002	-10000	0	-10000	0	0
UBE2I	0.022	0.004	-10000	0	-10000	0	0
NUP153	0.022	0.004	-10000	0	-10000	0	0
KPNA2	0.022	0.004	-10000	0	-10000	0	0
PIAS4	0.022	0.004	-10000	0	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.021	0.006	-10000	0	-9999	0
PLK4	0.022	0.011	0.23	1	-9999	1
regulation of centriole replication	-0.01	0.004	-10000	0	-9999	0

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.032	0.007	-10000	0	-10000	0	0
FBXW11	0.021	0.006	-10000	0	-10000	0	0
NF kappa B1 p50/c-Rel	0.019	0.01	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.022	0.038	-10000	0	-10000	0	0
NFKBIA	0.011	0.022	-10000	0	-0.22	1	1
MAPK14	0.022	0.004	-10000	0	-10000	0	0
NF kappa B1 p105/p50	0.019	0.009	-10000	0	-10000	0	0
ARRB2	0.01	0.003	-10000	0	-10000	0	0
REL	0.021	0.007	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	0.02	0.009	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	0.02	0.008	-10000	0	-10000	0	0
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
NF kappa B1 p50 dimer	0.017	0.028	0.42	2	-10000	0	2
PIK3R1	0.021	0.006	-10000	0	-10000	0	0
NFKB1	-0.008	0.027	0.58	1	-10000	0	1
RELA	0.023	0.002	-10000	0	-10000	0	0
positive regulation of anti-apoptosis	0.018	0.033	0.24	1	-0.22	1	2
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.022	0.043	-10000	0	-10000	0	0
SRC	0.022	0.004	-10000	0	-10000	0	0
PI3K	0.017	0.017	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.018	0.033	0.24	1	-0.23	1	2
IKBKB	0.021	0.017	0.38	1	-10000	0	1
beta TrCP1/SCF ubiquitin ligase complex	0.021	0.006	-10000	0	-10000	0	0
SYK	0.022	0.004	-10000	0	-10000	0	0
I kappa B alpha/PIK3R1	0.023	0.034	-10000	0	-0.25	1	1
cell death	0.021	0.041	-10000	0	-10000	0	0
NF kappa B1 p105/c-Rel	0.019	0.01	-10000	0	-10000	0	0
LCK	0.021	0.025	-10000	0	-0.53	1	1
BCL3	0.022	0.004	-10000	0	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.022	0.004	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.01	0.006	-10000	0	-10000	0	0
MDM2/SUMO1	0.03	0.032	0.24	1	-0.26	1	2
HDAC4	0.022	0.004	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	-0.01	0.006	-10000	0	-10000	0	0
SUMO1	0.022	0.003	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1	0.008	0.007	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
XPO1	0.005	0.002	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
RAN	0.023	0.002	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.023	0.002	-10000	0	-10000	0	0
SUMO1/HDAC4	0.031	0.029	-10000	0	-0.24	1	1
SUMO1/HDAC1	0.031	0.029	-10000	0	-0.26	1	1
RANGAP1	0.022	0.004	-10000	0	-10000	0	0
MDM2/SUMO1/SUMO1	0.053	0.021	0.25	1	-10000	0	1
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.01	0.003	-10000	0	-10000	0	0
Ran/GTP	0.021	0.028	-10000	0	-0.24	1	1
EntrezGene:23225	0	0	-10000	0	-10000	0	0
MDM2	0.023	0.016	0.38	1	-10000	0	1
UBE2I	0.022	0.004	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.032	0.053	0.24	3	-10000	0	3
NPC	0.013	0.001	-10000	0	-10000	0	0
PIAS2	0.022	0.005	-10000	0	-10000	0	0
PIAS1	0.023	0.002	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0

×

E-cadherin signaling events

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
E-cadherin/beta catenin-gamma catenin	0.041	0.015	-9999	-9999
E-cadherin/beta catenin	0.031	0.01	-9999	-9999
CTNNB1	0.021	0.006	-9999	-9999
JUP	0.022	0.003	-9999	-9999
CDH1	0.022	0.005	-9999	-9999

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.032	0.009	-10000	0	-9999	0
FBXW11	0.021	0.006	-10000	0	-9999	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-10000	0	-9999	0
beta TrCP1/SCF ubiquitin ligase complex	0.021	0.006	-10000	0	-9999	0
CHUK	0.022	0.005	-10000	0	-9999	0
NF kappa B2 p100/RelB	0.06	0.025	-10000	0	-9999	0
NFKB1	0.022	0.005	-10000	0	-9999	0
MAP3K14	0.022	0.004	-10000	0	-9999	0
NF kappa B1 p50/RelB	0.032	0.014	0.27	1	-9999	1
RELB	0.023	0.016	0.38	1	-9999	1
NFKB2	0.022	0.005	-10000	0	-9999	0
NF kappa B2 p52/RelB	0.029	0.012	0.24	1	-9999	1
regulation of B cell activation	0.029	0.012	0.23	1	-9999	1

pid_entity	TCGA.XC.AA0X	TCGA.O2.A5IB	TCGA.O2.A52W	TCGA.O2.A52V
109_MAP3K5	0.05	-0.17	0.02	0.02
47_PPARGC1A	0.023	0	0.023	0.023
105_BMP4	0.023	0.023	0.023	0.023
105_BMP6	0.023	0.023	0.023	0.023
105_BMP7	0.23	0.023	0.23	0.23
105_BMP2	0.023	-0.53	0.023	0.023
131_RELN/VLDLR	0.059	0.059	0.059	0.059
30_TGFB1/TGF beta receptor Type II	0.021	0.028	0.021	0.021
84_STAT5B	0.023	-0.34	0.024	0.024
84_STAT5A	0.023	-0.34	0.024	0.024