PARADIGM pathway analysis of mRNASeq expression and copy number data - Kidney Renal Clear Cell Carcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
Nephrin/Neph1 signaling in the kidney podocyte	243
HIF-1-alpha transcription factor network	159
EGFR-dependent Endothelin signaling events	140
TCR signaling in naïve CD8+ T cells	134
FOXA2 and FOXA3 transcription factor networks	131
PDGFR-alpha signaling pathway	111
TCGA08_retinoblastoma	98
Syndecan-4-mediated signaling events	91
TCGA08_p53	89
Glypican 1 network	82

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
Nephrin/Neph1 signaling in the kidney podocyte	0.4691	243	8265	34	-0.49	0.029	1000	-1000	-0.048	-1000
HIF-1-alpha transcription factor network	0.3069	159	12102	76	-0.99	0.044	1000	-1000	-0.16	-1000
EGFR-dependent Endothelin signaling events	0.2703	140	2945	21	-0.54	0.041	1000	-1000	-0.053	-1000
TCR signaling in naïve CD8+ T cells	0.2587	134	12522	93	-0.41	0.19	1000	-1000	-0.065	-1000
FOXA2 and FOXA3 transcription factor networks	0.2529	131	6026	46	-1.1	0.034	1000	-1000	-0.1	-1000
PDGFR-alpha signaling pathway	0.2143	111	4909	44	-0.21	0.035	1000	-1000	-0.05	-1000
TCGA08_retinoblastoma	0.1892	98	787	8	-0.5	0.13	1000	-1000	-0.006	-1000
Syndecan-4-mediated signaling events	0.1757	91	6156	67	-0.37	0.083	1000	-1000	-0.05	-1000
TCGA08_p53	0.1718	89	629	7	-0.35	0.19	1000	-1000	-0.012	-1000
Glypican 1 network	0.1583	82	3948	48	-0.38	0.045	1000	-1000	-0.047	-1000
Aurora B signaling	0.1564	81	5428	67	-0.23	0.04	1000	-1000	-0.055	-1000
IL12-mediated signaling events	0.1525	79	6921	87	-0.38	0.097	1000	-1000	-0.11	-1000
amb2 Integrin signaling	0.1409	73	5993	82	-0.43	0.037	1000	-1000	-0.047	-1000
BMP receptor signaling	0.1371	71	5798	81	-0.5	0.052	1000	-1000	-0.081	-1000
Aurora C signaling	0.1313	68	476	7	-0.22	0.026	1000	-1000	-0.015	-1000
Glypican 2 network	0.1178	61	244	4	-0.03	-1000	1000	-1000	-0.004	-1000
FOXM1 transcription factor network	0.1158	60	3088	51	-0.48	0.029	1000	-1000	-0.11	-1000
JNK signaling in the CD4+ TCR pathway	0.1081	56	955	17	-0.19	0.028	1000	-1000	-0.046	-1000
Caspase cascade in apoptosis	0.1004	52	3890	74	-0.29	0.073	1000	-1000	-0.046	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0965	50	1670	33	-0.49	0.053	1000	-1000	-0.042	-1000
IL4-mediated signaling events	0.0946	49	4528	91	-0.77	0.47	1000	-1000	-0.13	-1000
Syndecan-1-mediated signaling events	0.0869	45	1539	34	-0.21	0.029	1000	-1000	-0.063	-1000
Fc-epsilon receptor I signaling in mast cells	0.0792	41	4000	97	-0.24	0.039	1000	-1000	-0.076	-1000
Arf6 signaling events	0.0753	39	2418	62	-0.54	0.062	1000	-1000	-0.044	-1000
Effects of Botulinum toxin	0.0734	38	1001	26	-0.2	0.04	1000	-1000	-0.027	-1000
HIF-2-alpha transcription factor network	0.0714	37	1608	43	-0.45	0.21	1000	-1000	-0.066	-1000
Calcium signaling in the CD4+ TCR pathway	0.0714	37	1152	31	-0.33	0.028	1000	-1000	-0.055	-1000
Reelin signaling pathway	0.0695	36	2030	56	-0.16	0.077	1000	-1000	-0.068	-1000
Signaling events mediated by the Hedgehog family	0.0676	35	1839	52	-0.24	0.064	1000	-1000	-0.056	-1000
LPA4-mediated signaling events	0.0637	33	396	12	-0.085	0.009	1000	-1000	-0.028	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0637	33	1815	54	-0.38	0.04	1000	-1000	-0.079	-1000
IL27-mediated signaling events	0.0618	32	1666	51	-0.59	0.048	1000	-1000	-0.058	-1000
Ephrin A reverse signaling	0.0598	31	217	7	-0.022	0.013	1000	-1000	-0.013	-1000
IL2 signaling events mediated by STAT5	0.0579	30	681	22	-0.25	0.034	1000	-1000	-0.061	-1000
Coregulation of Androgen receptor activity	0.0560	29	2277	76	-0.84	0.052	1000	-1000	-0.028	-1000
p75(NTR)-mediated signaling	0.0560	29	3695	125	-0.29	0.076	1000	-1000	-0.083	-1000
PLK1 signaling events	0.0560	29	2545	85	-0.16	0.041	1000	-1000	-0.054	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0560	29	2008	68	-0.28	0.052	1000	-1000	-0.11	-1000
S1P1 pathway	0.0541	28	1043	36	-0.21	0.028	1000	-1000	-0.057	-1000
Glucocorticoid receptor regulatory network	0.0463	24	2788	114	-0.33	0.14	1000	-1000	-0.068	-1000
Ceramide signaling pathway	0.0463	24	1830	76	-0.54	0.2	1000	-1000	-0.046	-1000
VEGFR1 specific signals	0.0463	24	1399	56	-0.27	0.029	1000	-1000	-0.06	-1000
Integrins in angiogenesis	0.0444	23	1956	84	-0.25	0.065	1000	-1000	-0.074	-1000
BCR signaling pathway	0.0444	23	2327	99	-0.19	0.056	1000	-1000	-0.073	-1000
IL23-mediated signaling events	0.0444	23	1419	60	-0.22	0.028	1000	-1000	-0.085	-1000
Signaling events mediated by PTP1B	0.0425	22	1688	76	-0.55	0.067	1000	-1000	-0.058	-1000
IL2 signaling events mediated by PI3K	0.0425	22	1309	58	-0.25	0.045	1000	-1000	-0.058	-1000
Wnt signaling	0.0425	22	158	7	-0.042	0.027	1000	-1000	-0.036	-1000
Noncanonical Wnt signaling pathway	0.0405	21	546	26	-0.096	0.028	1000	-1000	-0.06	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0405	21	968	45	-0.31	0.075	1000	-1000	-0.067	-1000
Regulation of Telomerase	0.0405	21	2164	102	-0.54	0.059	1000	-1000	-0.075	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0405	21	1901	88	-0.17	0.037	1000	-1000	-0.084	-1000
FoxO family signaling	0.0386	20	1327	64	-0.55	0.086	1000	-1000	-0.062	-1000
Visual signal transduction: Rods	0.0386	20	1046	52	-0.13	0.041	1000	-1000	-0.064	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0386	20	1610	78	-0.23	0.043	1000	-1000	-0.063	-1000
Thromboxane A2 receptor signaling	0.0367	19	2011	105	-0.54	0.04	1000	-1000	-0.052	-1000
Syndecan-2-mediated signaling events	0.0347	18	1302	69	-0.43	0.061	1000	-1000	-0.046	-1000
EPO signaling pathway	0.0347	18	1041	55	-0.14	0.035	1000	-1000	-0.066	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0347	18	2183	120	-0.11	0.078	1000	-1000	-0.063	-1000
Signaling mediated by p38-alpha and p38-beta	0.0328	17	774	44	-0.041	0.05	1000	-1000	-0.036	-1000
Endothelins	0.0309	16	1617	96	-0.33	0.042	1000	-1000	-0.067	-1000
LPA receptor mediated events	0.0309	16	1662	102	-0.21	0.046	1000	-1000	-0.065	-1000
Presenilin action in Notch and Wnt signaling	0.0290	15	964	61	-0.13	0.082	1000	-1000	-0.069	-1000
IFN-gamma pathway	0.0290	15	1040	68	-0.21	0.041	1000	-1000	-0.072	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0290	15	1154	74	-0.54	0.098	1000	-1000	-0.091	-1000
Signaling events regulated by Ret tyrosine kinase	0.0270	14	1174	82	-0.037	0.029	1000	-1000	-0.08	-1000
IL6-mediated signaling events	0.0270	14	1097	75	-0.2	0.053	1000	-1000	-0.058	-1000
Class I PI3K signaling events	0.0270	14	1059	73	-0.26	0.078	1000	-1000	-0.054	-1000
Canonical Wnt signaling pathway	0.0251	13	675	51	-0.13	0.094	1000	-1000	-0.06	-1000
Nongenotropic Androgen signaling	0.0251	13	724	52	-0.095	0.043	1000	-1000	-0.044	-1000
Regulation of Androgen receptor activity	0.0251	13	949	70	-0.91	0.052	1000	-1000	-0.051	-1000
Regulation of nuclear SMAD2/3 signaling	0.0232	12	1719	136	-0.28	0.096	1000	-1000	-0.059	-1000
PLK2 and PLK4 events	0.0232	12	36	3	0.006	0.025	1000	-1000	-0.015	-1000
Aurora A signaling	0.0232	12	738	60	-0.13	0.058	1000	-1000	-0.034	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0232	12	461	37	-0.14	0.057	1000	-1000	-0.037	-1000
S1P5 pathway	0.0232	12	211	17	-0.062	0.028	1000	-1000	-0.029	-1000
Plasma membrane estrogen receptor signaling	0.0232	12	1108	86	-0.13	0.052	1000	-1000	-0.08	-1000
S1P3 pathway	0.0232	12	524	42	-0.21	0.049	1000	-1000	-0.043	-1000
ErbB4 signaling events	0.0212	11	762	69	-0.16	0.096	1000	-1000	-0.059	-1000
FAS signaling pathway (CD95)	0.0212	11	555	47	-0.24	0.047	1000	-1000	-0.045	-1000
TCGA08_rtk_signaling	0.0212	11	307	26	-0.22	0.053	1000	-1000	-0.025	-1000
ceramide signaling pathway	0.0193	10	509	49	-0.054	0.044	1000	-1000	-0.05	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0193	10	1253	125	-0.21	0.041	1000	-1000	-0.067	-1000
S1P4 pathway	0.0193	10	266	25	-0.062	0.037	1000	-1000	-0.04	-1000
E-cadherin signaling events	0.0193	10	54	5	0.007	0.024	1000	-1000	-0.003	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0174	9	274	28	-0.062	0.047	1000	-1000	-0.033	-1000
a4b1 and a4b7 Integrin signaling	0.0174	9	45	5	0.012	0.028	1000	-1000	0	-1000
Visual signal transduction: Cones	0.0154	8	332	38	-0.012	0.044	1000	-1000	-0.019	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0154	8	733	85	-0.04	0.076	1000	-1000	-0.057	-1000
mTOR signaling pathway	0.0154	8	431	53	-0.059	0.05	1000	-1000	-0.054	-1000
Syndecan-3-mediated signaling events	0.0154	8	302	35	-0.009	0.076	1000	-1000	-0.05	-1000
E-cadherin signaling in keratinocytes	0.0154	8	382	43	-0.21	0.038	1000	-1000	-0.058	-1000
Ephrin B reverse signaling	0.0135	7	341	48	-0.047	0.052	1000	-1000	-0.043	-1000
Canonical NF-kappaB pathway	0.0116	6	267	39	-0.098	0.055	1000	-1000	-0.049	-1000
IL1-mediated signaling events	0.0116	6	373	62	-0.036	0.062	1000	-1000	-0.075	-1000
E-cadherin signaling in the nascent adherens junction	0.0116	6	495	76	-0.033	0.049	1000	-1000	-0.08	-1000
Signaling events mediated by PRL	0.0116	6	233	34	-0.037	0.06	1000	-1000	-0.051	-1000
ErbB2/ErbB3 signaling events	0.0097	5	355	65	-0.11	0.04	1000	-1000	-0.057	-1000
Cellular roles of Anthrax toxin	0.0097	5	214	39	-0.009	0.037	1000	-1000	-0.029	-1000
Insulin-mediated glucose transport	0.0097	5	171	32	-0.036	0.054	1000	-1000	-0.035	-1000
Signaling events mediated by HDAC Class III	0.0097	5	218	40	-0.052	0.052	1000	-1000	-0.026	-1000
EPHB forward signaling	0.0097	5	443	85	-0.046	0.069	1000	-1000	-0.086	-1000
Regulation of p38-alpha and p38-beta	0.0097	5	278	54	-0.021	0.064	1000	-1000	-0.056	-1000
Arf6 trafficking events	0.0097	5	382	71	-0.11	0.059	1000	-1000	-0.05	-1000
PDGFR-beta signaling pathway	0.0097	5	520	97	-0.012	0.081	1000	-1000	-0.073	-1000
Class IB PI3K non-lipid kinase events	0.0097	5	15	3	-0.023	0.023	1000	-1000	-0.008	-1000
p38 MAPK signaling pathway	0.0097	5	251	44	-0.062	0.055	1000	-1000	-0.043	-1000
Ras signaling in the CD4+ TCR pathway	0.0097	5	100	17	-0.006	0.052	1000	-1000	-0.037	-1000
Signaling mediated by p38-gamma and p38-delta	0.0077	4	70	15	0	0.03	1000	-1000	-0.032	-1000
IGF1 pathway	0.0077	4	233	57	-0.054	0.075	1000	-1000	-0.064	-1000
Insulin Pathway	0.0077	4	298	74	-0.033	0.077	1000	-1000	-0.066	-1000
BARD1 signaling events	0.0058	3	208	57	-0.081	0.073	1000	-1000	-0.075	-1000
Hedgehog signaling events mediated by Gli proteins	0.0058	3	249	65	-0.005	0.097	1000	-1000	-0.056	-1000
Class I PI3K signaling events mediated by Akt	0.0058	3	228	68	-0.036	0.053	1000	-1000	-0.049	-1000
Nectin adhesion pathway	0.0058	3	191	63	0	0.056	1000	-1000	-0.062	-1000
Osteopontin-mediated events	0.0039	2	105	38	0	0.08	1000	-1000	-0.055	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0039	2	149	52	-0.013	0.094	1000	-1000	-0.046	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0039	2	240	83	-0.036	0.068	1000	-1000	-0.057	-1000
Retinoic acid receptors-mediated signaling	0.0039	2	129	58	-0.021	0.051	1000	-1000	-0.056	-1000
Paxillin-dependent events mediated by a4b1	0.0039	2	76	36	-0.051	0.053	1000	-1000	-0.044	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0019	1	38	23	-0.029	0.054	1000	-1000	-0.042	-1000
Signaling events mediated by HDAC Class II	0.0019	1	109	75	-0.038	0.059	1000	-1000	-0.034	-1000
Circadian rhythm pathway	0.0019	1	24	22	-0.012	0.065	1000	-1000	-0.036	-1000
Arf6 downstream pathway	0.0019	1	83	43	-0.045	0.046	1000	-1000	-0.043	-1000
Signaling events mediated by HDAC Class I	0.0019	1	192	104	-0.055	0.073	1000	-1000	-0.046	-1000
Atypical NF-kappaB pathway	0.0019	1	61	31	0	0.036	1000	-1000	-0.035	-1000
Arf1 pathway	0.0019	1	84	54	0	0.047	1000	-1000	-0.027	-1000
TRAIL signaling pathway	0.0000	0	34	48	0	0.07	1000	-1000	-0.048	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	7	27	0	0.067	1000	-1000	-0.046	-1000
Rapid glucocorticoid signaling	0.0000	0	9	20	-0.007	0.035	1000	-1000	-0.012	-1000
Alternative NF-kappaB pathway	0.0000	0	10	13	0	0.059	1000	-1000	-0.003	-1000
Total	NA	3530	191557	7203	-27	-990	131000	-131000	-7	-131000

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.38	0.22	0.5	379	-10000	0	379
KIRREL	-0.059	0.082	-10000	0	-0.6	8	8
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.38	0.22	-10000	0	-0.5	379	379
PLCG1	0.028	0.006	-10000	0	-10000	0	0
ARRB2	0.027	0.029	-10000	0	-0.62	1	1
WASL	0.026	0.009	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.4	0.27	-10000	0	-0.51	400	400
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.33	0.23	-10000	0	-0.44	375	375
FYN	-0.38	0.24	0.26	1	-0.48	404	405
mol:Ca2+	-0.39	0.27	-10000	0	-0.51	397	397
mol:DAG	-0.39	0.27	-10000	0	-0.51	397	397
NPHS2	-0.33	0.31	-10000	0	-0.66	235	235
mol:IP3	-0.39	0.27	-10000	0	-0.51	397	397
regulation of endocytosis	-0.35	0.24	-10000	0	-0.46	397	397
Nephrin/NEPH1/podocin/Cholesterol	-0.4	0.26	-10000	0	-0.51	404	404
establishment of cell polarity	-0.38	0.22	-10000	0	-0.5	379	379
Nephrin/NEPH1/podocin/NCK1-2	-0.36	0.26	-10000	0	-0.62	210	210
Nephrin/NEPH1/beta Arrestin2	-0.36	0.24	-10000	0	-0.47	397	397
NPHS1	-0.49	0.27	-10000	0	-0.64	392	392
Nephrin/NEPH1/podocin	-0.38	0.25	-10000	0	-0.48	404	404
TJP1	0.029	0.003	-10000	0	-10000	0	0
NCK1	0.026	0.029	-10000	0	-0.61	1	1
NCK2	0.028	0.005	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.39	0.27	-10000	0	-0.51	397	397
CD2AP	0.028	0.006	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.39	0.27	-10000	0	-0.51	398	398
GRB2	0.028	0.005	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.37	0.24	0.28	1	-0.48	398	399
cytoskeleton organization	-0.42	0.27	-10000	0	-0.56	358	358
Nephrin/NEPH1	-0.27	0.17	-10000	0	-0.37	379	379
Nephrin/NEPH1/ZO-1	-0.3	0.19	-10000	0	-0.41	377	377

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.79	0.46	-10000	0	-1.2	239	239
HDAC7	0.025	0.01	-10000	0	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.58	0.31	-10000	0	-0.88	193	193
SMAD4	0.029	0.005	-10000	0	-10000	0	0
ID2	-0.79	0.46	-10000	0	-1.2	239	239
AP1	0.028	0.074	-10000	0	-0.44	12	12
ABCG2	-0.79	0.46	-10000	0	-1.2	240	240
HIF1A	-0.11	0.072	-10000	0	-0.74	2	2
TFF3	-0.8	0.46	-10000	0	-1.2	243	243
GATA2	0.014	0.09	-10000	0	-0.58	11	11
AKT1	-0.098	0.06	-10000	0	-0.31	1	1
response to hypoxia	-0.12	0.059	-10000	0	-0.34	7	7
MCL1	-0.79	0.46	-10000	0	-1.2	236	236
NDRG1	-0.79	0.46	-10000	0	-1.2	240	240
SERPINE1	-0.8	0.49	-10000	0	-1.2	245	245
FECH	-0.79	0.46	-10000	0	-1.2	242	242
FURIN	-0.79	0.46	-10000	0	-1.2	240	240
NCOA2	0.013	0.079	-10000	0	-0.61	8	8
EP300	-0.1	0.075	-10000	0	-0.32	17	17
HMOX1	-0.8	0.47	-10000	0	-1.2	246	246
BHLHE40	-0.79	0.46	-10000	0	-1.2	239	239
BHLHE41	-0.84	0.49	-10000	0	-1.2	261	261
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.098	0.085	-10000	0	-0.52	2	2
ENG	-0.086	0.086	0.43	1	-0.48	2	3
JUN	0.028	0.007	-10000	0	-10000	0	0
RORA	-0.79	0.46	-10000	0	-1.2	243	243
ABCB1	-0.26	0.39	-10000	0	-1.3	64	64
TFRC	-0.79	0.46	-10000	0	-1.2	241	241
CXCR4	-0.86	0.5	-10000	0	-1.2	274	274
TF	-0.83	0.5	-10000	0	-1.2	251	251
CITED2	-0.79	0.46	-10000	0	-1.2	239	239
HIF1A/ARNT	-0.94	0.64	-10000	0	-1.4	266	266
LDHA	-0.079	0.12	-10000	0	-0.81	10	10
ETS1	-0.79	0.46	-10000	0	-1.2	240	240
PGK1	-0.79	0.46	-10000	0	-1.2	240	240
NOS2	-0.79	0.46	-10000	0	-1.2	241	241
ITGB2	-0.82	0.48	-10000	0	-1.2	256	256
ALDOA	-0.79	0.46	-10000	0	-1.2	238	238
Cbp/p300/CITED2	-0.79	0.45	-10000	0	-1.2	226	226
FOS	0.012	0.096	-10000	0	-0.6	12	12
HK2	-0.93	0.49	-10000	0	-1.3	304	304
SP1	0.021	0.043	-10000	0	-10000	0	0
GCK	-0.17	0.16	-10000	0	-0.88	10	10
HK1	-0.79	0.46	-10000	0	-1.2	240	240
NPM1	-0.76	0.46	-10000	0	-1.2	225	225
EGLN1	-0.79	0.46	-10000	0	-1.2	236	236
CREB1	0.034	0.009	-10000	0	-10000	0	0
PGM1	-0.79	0.46	-10000	0	-1.2	240	240
SMAD3	0.03	0.003	-10000	0	-10000	0	0
EDN1	-0.11	0.13	-10000	0	-0.69	7	7
IGFBP1	-0.82	0.5	-10000	0	-1.2	246	246
VEGFA	-0.62	0.32	-10000	0	-0.93	199	199
HIF1A/JAB1	-0.062	0.056	-10000	0	-0.56	2	2
CP	-0.93	0.5	-10000	0	-1.3	311	311
CXCL12	-0.8	0.46	-10000	0	-1.2	244	244
COPS5	0.024	0.009	-10000	0	-10000	0	0
SMAD3/SMAD4	0.044	0.008	-10000	0	-10000	0	0
BNIP3	-0.79	0.46	-10000	0	-1.2	240	240
EGLN3	-0.98	0.46	-10000	0	-1.3	327	327
CA9	-0.99	0.45	-10000	0	-1.3	338	338
TERT	-0.81	0.47	-10000	0	-1.2	245	245
ENO1	-0.79	0.46	-10000	0	-1.2	243	243
PFKL	-0.79	0.46	-10000	0	-1.2	238	238
NCOA1	0.028	0.005	-10000	0	-10000	0	0
ADM	-0.84	0.48	-10000	0	-1.2	261	261
ARNT	-0.11	0.054	-10000	0	-10000	0	0
HNF4A	-0.018	0.17	-10000	0	-0.61	38	38
ADFP	-0.79	0.46	-10000	0	-1.2	261	261
SLC2A1	-0.55	0.28	-10000	0	-0.86	146	146
LEP	-0.8	0.47	-10000	0	-1.2	246	246
HIF1A/ARNT/Cbp/p300	-0.6	0.31	-10000	0	-0.91	194	194
EPO	-0.49	0.3	-10000	0	-0.83	167	167
CREBBP	-0.1	0.074	-10000	0	-0.33	13	13
HIF1A/ARNT/Cbp/p300/HDAC7	-0.62	0.34	-10000	0	-0.95	192	192
PFKFB3	-0.79	0.46	-10000	0	-1.2	240	240
NT5E	-0.79	0.46	-10000	0	-1.2	242	242

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.028	0.024	-9999	-0.5	1	1
EGFR	0.019	0.06	-9999	-0.52	6	6
EGF/EGFR	-0.28	0.12	-9999	-0.33	411	411
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.27	0.13	-9999	-0.33	389	389
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.027	0.024	-9999	-0.5	1	1
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.54	0.19	-9999	-0.61	460	460
EGF/EGFR dimer/SHC	-0.32	0.14	-9999	-0.39	398	398
mol:GDP	-0.27	0.13	-9999	-0.33	389	389
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.01	0.097	-9999	-0.51	17	17
GRB2/SOS1	0.041	0.009	-9999	-10000	0	0
HRAS/GTP	-0.25	0.12	-9999	-0.54	6	6
SHC1	0.027	0.006	-9999	-10000	0	0
HRAS/GDP	-0.25	0.12	-9999	-0.54	6	6
FRAP1	-0.26	0.11	-9999	-0.32	389	389
EGF/EGFR dimer	-0.39	0.16	-9999	-0.43	454	454
SOS1	0.028	0.005	-9999	-10000	0	0
GRB2	0.028	0.005	-9999	-10000	0	0
ETA receptor/Endothelin-1	0.027	0.076	-9999	-0.37	18	18

TCR signaling in naïve CD8+ T 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
GRB2/SOS1/SHC	-0.21	0.27	0.3	6	-0.52	196	202
FYN	-0.25	0.34	0.42	13	-0.62	203	216
LAT/GRAP2/SLP76	-0.25	0.31	0.34	4	-0.59	201	205
IKBKB	0.027	0.008	-10000	0	-10000	0	0
AKT1	-0.18	0.27	0.44	21	-0.45	212	233
B2M	0.025	0.007	-10000	0	-10000	0	0
IKBKG	-0.051	0.082	0.15	13	-0.17	63	76
MAP3K8	0.026	0.033	-10000	0	-0.5	2	2
mol:Ca2+	-0.084	0.052	0.073	10	-0.12	283	293
integrin-mediated signaling pathway	0.026	0.058	-10000	0	-0.31	15	15
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.27	0.37	0.49	16	-0.66	213	229
TRPV6	-0.41	0.42	0.74	44	-0.61	394	438
CD28	-0.014	0.14	-10000	0	-0.51	38	38
SHC1	-0.27	0.34	0.39	8	-0.62	223	231
receptor internalization	-0.29	0.34	0.48	1	-0.64	227	228
PRF1	-0.27	0.36	0.41	1	-0.74	158	159
KRAS	0.028	0.005	-10000	0	-10000	0	0
GRB2	0.028	0.005	-10000	0	-10000	0	0
COT/AKT1	-0.13	0.22	0.41	19	-0.36	191	210
LAT	-0.32	0.38	0.46	7	-0.7	231	238
EntrezGene:6955	-0.003	0.005	-10000	0	-10000	0	0
CD3D	-0.21	0.27	-10000	0	-0.51	228	228
CD3E	-0.19	0.26	-10000	0	-0.51	204	204
CD3G	-0.18	0.26	-10000	0	-0.51	200	200
RASGRP2	-0.012	0.028	0.089	5	-0.17	1	6
RASGRP1	-0.15	0.27	0.45	26	-0.44	189	215
HLA-A	0.022	0.035	-10000	0	-0.51	2	2
RASSF5	0.012	0.09	-10000	0	-0.5	15	15
RAP1A/GTP/RAPL	0.027	0.059	-10000	0	-0.31	15	15
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	-0.004	0.14	0.23	61	-0.13	5	66
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.11	0.11	-10000	0	-0.25	162	162
PRKCA	-0.1	0.16	0.18	32	-0.28	167	199
GRAP2	-0.008	0.14	-10000	0	-0.51	35	35
mol:IP3	-0.11	0.29	0.23	155	-0.43	192	347
EntrezGene:6957	-0.003	0.006	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.24	0.3	0.28	1	-0.56	221	222
ORAI1	0.19	0.27	0.66	6	-0.59	44	50
CSK	-0.28	0.34	0.38	5	-0.63	225	230
B7 family/CD28	-0.3	0.39	0.32	2	-0.73	205	207
CHUK	0.028	0.006	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.32	0.38	0.24	1	-0.71	227	228
PTPN6	-0.27	0.33	0.28	4	-0.63	211	215
VAV1	-0.32	0.38	0.42	7	-0.7	228	235
Monovalent TCR/CD3	-0.21	0.26	-10000	0	-0.5	221	221
CBL	0.027	0.028	-10000	0	-0.61	1	1
LCK	-0.26	0.35	0.44	11	-0.63	211	222
PAG1	-0.28	0.33	0.32	3	-0.63	224	227
RAP1A	0.028	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.3	0.37	-10000	0	-0.7	216	216
CD80	-0.095	0.22	-10000	0	-0.51	114	114
CD86	-0.06	0.2	-10000	0	-0.51	81	81
PDK1/CARD11/BCL10/MALT1	-0.13	0.15	0.19	1	-0.3	172	173
HRAS	0.028	0.024	-10000	0	-0.5	1	1
GO:0035030	-0.25	0.31	0.42	3	-0.58	212	215
CD8A	-0.22	0.27	-10000	0	-0.51	230	230
CD8B	-0.17	0.26	-10000	0	-0.51	184	184
PTPRC	-0.03	0.16	-10000	0	-0.51	53	53
PDK1/PKC theta	-0.22	0.33	0.54	23	-0.56	209	232
CSK/PAG1	-0.27	0.33	0.42	5	-0.63	208	213
SOS1	0.028	0.005	-10000	0	-10000	0	0
peptide-MHC class I	0.032	0.029	-10000	0	-0.37	2	2
GRAP2/SLP76	-0.26	0.33	0.3	2	-0.63	202	204
STIM1	0.11	0.11	0.96	1	-0.63	3	4
RAS family/GTP	-0.032	0.14	0.31	31	-0.18	41	72
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.31	0.36	0.49	1	-0.68	227	228
mol:DAG	-0.16	0.21	0.14	2	-0.39	205	207
RAP1A/GDP	0.003	0.083	0.19	33	-10000	0	33
PLCG1	0.028	0.006	-10000	0	-10000	0	0
CD247	-0.15	0.25	-10000	0	-0.51	166	166
cytotoxic T cell degranulation	-0.26	0.35	0.41	1	-0.71	159	160
RAP1A/GTP	-0.005	0.01	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.22	0.31	0.43	19	-0.54	213	232
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.18	0.36	0.26	116	-0.58	199	315
NRAS	0.028	0.005	-10000	0	-10000	0	0
ZAP70	-0.26	0.26	-10000	0	-0.5	276	276
GRB2/SOS1	0.041	0.009	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.26	0.31	0.28	3	-0.6	209	212
MALT1	0.028	0.005	-10000	0	-10000	0	0
TRAF6	0.029	0.003	-10000	0	-10000	0	0
CD8 heterodimer	-0.25	0.33	-10000	0	-0.6	236	236
CARD11	-0.077	0.21	-10000	0	-0.5	98	98
PRKCB	-0.11	0.16	0.17	30	-0.28	175	205
PRKCE	-0.1	0.16	0.17	31	-0.28	172	203
PRKCQ	-0.26	0.37	0.46	22	-0.64	210	232
LCP2	-0.009	0.12	-10000	0	-0.5	29	29
BCL10	0.028	0.005	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.15	0.23	0.42	22	-0.38	212	234
IKK complex	-0.002	0.15	0.27	64	-0.13	6	70
RAS family/GDP	-0.012	0.013	-10000	0	-10000	0	0
MAP3K14	-0.099	0.17	0.36	18	-0.28	163	181
PDPK1	-0.16	0.26	0.47	22	-0.43	206	228
TCR/CD3/MHC I/CD8/Fyn	-0.3	0.36	0.44	1	-0.69	217	218

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.44	0.4	-10000	0	-0.98	130	130
PCK1	-0.9	0.66	-10000	0	-1.3	313	313
HNF4A	-0.51	0.47	-10000	0	-1.2	131	131
KCNJ11	-0.45	0.43	-10000	0	-1	131	131
AKT1	-0.21	0.2	-10000	0	-0.53	56	56
response to starvation	-0.013	0.024	-10000	0	-10000	0	0
DLK1	-0.54	0.5	-10000	0	-1.1	174	174
NKX2-1	-0.086	0.18	-10000	0	-0.7	4	4
ACADM	-0.44	0.4	-10000	0	-0.98	133	133
TAT	-0.48	0.3	-10000	0	-0.75	224	224
CEBPB	-0.022	0.081	-10000	0	-0.56	8	8
CEBPA	-0.023	0.084	-10000	0	-0.54	10	10
TTR	-0.84	0.46	0.43	1	-1.1	354	355
PKLR	-0.48	0.48	-10000	0	-1.1	138	138
APOA1	-0.53	0.47	-10000	0	-1.2	140	140
CPT1C	-0.44	0.4	-10000	0	-0.97	134	134
ALAS1	-0.23	0.21	-10000	0	-0.72	14	14
TFRC	-0.64	0.38	-10000	0	-0.9	289	289
FOXF1	0.019	0.066	-10000	0	-0.49	8	8
NF1	0.034	0.005	-10000	0	-10000	0	0
HNF1A (dimer)	-0.014	0.081	-10000	0	-0.44	8	8
CPT1A	-0.44	0.4	-10000	0	-0.98	132	132
HMGCS1	-0.43	0.4	-10000	0	-0.98	126	126
NR3C1	0.006	0.053	-10000	0	-0.57	1	1
CPT1B	-0.45	0.42	-10000	0	-0.99	140	140
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.029	0.007	-10000	0	-10000	0	0
GCK	-0.43	0.41	-10000	0	-0.99	127	127
CREB1	-0.04	0.08	-10000	0	-0.32	2	2
IGFBP1	-0.24	0.29	-10000	0	-0.73	92	92
PDX1	-0.2	0.2	-10000	0	-0.76	12	12
UCP2	-0.44	0.4	-10000	0	-0.98	132	132
ALDOB	-0.87	0.55	-10000	0	-1.1	382	382
AFP	-0.62	0.43	-10000	0	-0.76	378	378
BDH1	-0.56	0.49	-10000	0	-1.1	200	200
HADH	-0.44	0.42	-10000	0	-1	130	130
F2	-0.57	0.48	-10000	0	-1.1	165	165
HNF1A	-0.014	0.081	-10000	0	-0.45	8	8
G6PC	-0.76	0.62	-10000	0	-1.4	241	241
SLC2A2	-0.32	0.43	-10000	0	-1.4	50	50
INS	0	0.058	-10000	0	-10000	0	0
FOXA1	-0.3	0.25	-10000	0	-0.55	191	191
FOXA3	-0.55	0.29	-10000	0	-0.67	392	392
FOXA2	-0.51	0.48	-10000	0	-1.1	152	152
ABCC8	-0.45	0.42	-10000	0	-1	135	135
ALB	-1.1	0.42	-10000	0	-1.2	438	438

PDGFR-alpha signaling pathway

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
PDGFRA	-0.21	0.31	-10000	0	-0.61	193	193
PDGF/PDGFRA/CRKL	-0.14	0.23	-10000	0	-0.44	190	190
positive regulation of JUN kinase activity	-0.079	0.19	-10000	0	-0.34	171	171
CRKL	0.028	0.004	-10000	0	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.15	0.23	-10000	0	-0.44	196	196
AP1	-0.12	0.21	0.47	1	-1.1	11	12
mol:IP3	-0.15	0.23	-10000	0	-0.45	187	187
PLCG1	-0.16	0.23	-10000	0	-0.45	187	187
PDGF/PDGFRA/alphaV Integrin	-0.14	0.23	-10000	0	-0.44	184	184
RAPGEF1	0.028	0.005	-10000	0	-10000	0	0
CRK	0.028	0.005	-10000	0	-10000	0	0
mol:Ca2+	-0.15	0.23	-10000	0	-0.45	187	187
CAV3	0.012	0.044	-10000	0	-0.54	3	3
CAV1	-0.006	0.12	-10000	0	-0.5	30	30
SHC/Grb2/SOS1	-0.078	0.19	-10000	0	-0.34	171	171
PDGF/PDGFRA/Shf	-0.14	0.23	-10000	0	-0.44	192	192
FOS	-0.12	0.21	-10000	0	-1.1	11	11
JUN	-0.025	0.022	-10000	0	-10000	0	0
oligodendrocyte development	-0.14	0.23	-10000	0	-0.44	184	184
GRB2	0.028	0.005	-10000	0	-10000	0	0
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
mol:DAG	-0.15	0.23	-10000	0	-0.45	187	187
PDGF/PDGFRA	-0.21	0.31	-10000	0	-0.61	193	193
actin cytoskeleton reorganization	-0.14	0.23	-10000	0	-0.44	192	192
SRF	0.023	0.01	-10000	0	-10000	0	0
SHC1	0.027	0.006	-10000	0	-10000	0	0
PI3K	-0.1	0.2	-10000	0	-0.37	166	166
PDGF/PDGFRA/Crk/C3G	-0.11	0.21	-10000	0	-0.37	190	190
JAK1	-0.15	0.22	-10000	0	-0.44	192	192
ELK1/SRF	-0.11	0.17	-10000	0	-0.34	179	179
SHB	0.028	0.006	-10000	0	-10000	0	0
SHF	0.027	0.028	-10000	0	-0.61	1	1
CSNK2A1	0.035	0.016	-10000	0	-10000	0	0
GO:0007205	-0.17	0.23	-10000	0	-0.46	192	192
SOS1	0.028	0.005	-10000	0	-10000	0	0
Ras protein signal transduction	-0.079	0.19	-10000	0	-0.34	171	171
PDGF/PDGFRA/SHB	-0.14	0.23	-10000	0	-0.44	192	192
PDGF/PDGFRA/Caveolin-1	-0.16	0.23	-10000	0	-0.44	194	194
ITGAV	0.027	0.006	-10000	0	-10000	0	0
ELK1	-0.14	0.2	-10000	0	-0.41	185	185
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
PDGF/PDGFRA/Crk	-0.14	0.23	-10000	0	-0.44	191	191
JAK-STAT cascade	-0.15	0.22	-10000	0	-0.44	192	192
cell proliferation	-0.14	0.23	-10000	0	-0.44	192	192

TCGA08_retinoblastoma

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
CDKN2B	0.025	0.059	-10000	0	-0.51	6	6
CDKN2C	0.071	0.021	-10000	0	-10000	0	0
CDKN2A	-0.5	0.11	-10000	0	-0.52	489	489
CCND2	0.11	0.05	0.23	46	-10000	0	46
RB1	-0.13	0.059	0.29	1	-0.25	54	55
CDK4	0.13	0.058	0.26	47	-10000	0	47
CDK6	0.13	0.062	0.23	84	-0.16	1	85
G1/S progression	0.13	0.061	0.26	58	-0.29	1	59

Syndecan-4-mediated signaling events

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
PTK2	-0.1	0.16	-10000	0	-0.68	16	16
Syndecan-4/Syndesmos	-0.27	0.23	-10000	0	-0.52	169	169
positive regulation of JNK cascade	-0.32	0.25	-10000	0	-0.59	189	189
Syndecan-4/ADAM12	-0.34	0.28	-10000	0	-0.61	212	212
CCL5	-0.2	0.26	-10000	0	-0.5	217	217
Rac1/GDP	0.019	0.007	-10000	0	-10000	0	0
DNM2	0.029	0.003	-10000	0	-10000	0	0
ITGA5	-0.007	0.13	-10000	0	-0.5	34	34
SDCBP	0.027	0.007	-10000	0	-10000	0	0
PLG	-0.28	0.3	-10000	0	-0.57	265	265
ADAM12	-0.12	0.24	-10000	0	-0.5	136	136
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0.028	0.006	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.08	0.06	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	-0.28	0.23	-10000	0	-0.53	180	180
Syndecan-4/CXCL12/CXCR4	-0.34	0.27	-10000	0	-0.63	189	189
Syndecan-4/Laminin alpha3	-0.28	0.23	-10000	0	-0.52	178	178
MDK	-0.011	0.14	-10000	0	-0.51	38	38
Syndecan-4/FZD7	-0.27	0.23	-10000	0	-0.52	181	181
Syndecan-4/Midkine	-0.29	0.24	-10000	0	-0.59	141	141
FZD7	0.026	0.029	-10000	0	-0.61	1	1
Syndecan-4/FGFR1/FGF	-0.26	0.22	-10000	0	-0.55	110	110
THBS1	0.025	0.049	-10000	0	-0.61	3	3
integrin-mediated signaling pathway	-0.27	0.22	-10000	0	-0.51	180	180
positive regulation of MAPKKK cascade	-0.32	0.25	-10000	0	-0.59	189	189
Syndecan-4/TACI	-0.3	0.25	-10000	0	-0.53	222	222
CXCR4	-0.15	0.25	-10000	0	-0.5	174	174
cell adhesion	0.018	0.065	0.22	5	-0.25	9	14
Syndecan-4/Dynamin	-0.28	0.23	-10000	0	-0.52	174	174
Syndecan-4/TSP1	-0.28	0.23	-10000	0	-0.52	175	175
Syndecan-4/GIPC	-0.28	0.23	-10000	0	-0.52	179	179
Syndecan-4/RANTES	-0.37	0.27	-10000	0	-0.61	241	241
ITGB1	0.028	0.004	-10000	0	-10000	0	0
LAMA1	0.013	0.095	-10000	0	-0.54	14	14
LAMA3	0.022	0.058	-10000	0	-0.5	6	6
RAC1	0.026	0.009	-10000	0	-10000	0	0
PRKCA	0.083	0.13	0.99	9	-10000	0	9
Syndecan-4/alpha-Actinin	-0.28	0.23	-10000	0	-0.52	175	175
TFPI	0.019	0.067	-10000	0	-0.51	8	8
F2	-0.17	0.26	-10000	0	-0.5	191	191
alpha5/beta1 Integrin	0.014	0.1	-10000	0	-0.36	34	34
positive regulation of cell adhesion	-0.28	0.23	-10000	0	-0.57	123	123
ACTN1	0.025	0.029	-10000	0	-0.61	1	1
TNC	0.014	0.093	-10000	0	-0.61	11	11
Syndecan-4/CXCL12	-0.28	0.23	-10000	0	-0.53	181	181
FGF6	0.018	0.004	-10000	0	-10000	0	0
RHOA	0.021	0.013	-10000	0	-10000	0	0
CXCL12	0.018	0.078	-10000	0	-0.52	10	10
TNFRSF13B	-0.025	0.16	-10000	0	-0.5	50	50
FGF2	0.022	0.061	-10000	0	-0.59	5	5
FGFR1	0.026	0.008	-10000	0	-10000	0	0
Syndecan-4/PI-4-5-P2	-0.28	0.22	-10000	0	-0.5	212	212
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.003	0.14	-10000	0	-0.49	37	37
cell migration	-0.027	0.02	-10000	0	-10000	0	0
PRKCD	0.028	0.032	-10000	0	-0.49	1	1
vasculogenesis	-0.27	0.22	-10000	0	-0.5	176	176
SDC4	-0.29	0.24	-10000	0	-0.53	212	212
Syndecan-4/Tenascin C	-0.28	0.23	-10000	0	-0.53	180	180
Syndecan-4/PI-4-5-P2/PKC alpha	-0.063	0.047	-10000	0	-10000	0	0
Syndecan-4/Syntenin	-0.27	0.23	-10000	0	-0.52	171	171
MMP9	-0.21	0.26	-10000	0	-0.5	230	230
Rac1/GTP	0.018	0.066	0.22	5	-0.26	9	14
cytoskeleton organization	-0.26	0.22	-10000	0	-0.5	172	172
GIPC1	0.027	0.028	-10000	0	-0.61	1	1
Syndecan-4/TFPI	-0.28	0.23	-10000	0	-0.57	125	125

TCGA08_p53

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
CDKN2A	-0.35	0.085	0.19	3	-0.37	489	492
TP53	-0.1	0.071	-10000	0	-0.34	32	32
Senescence	-0.1	0.071	-10000	0	-0.34	32	32
Apoptosis	-0.1	0.071	-10000	0	-0.34	32	32
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.19	0.088	0.4	41	-10000	0	41
MDM4	0.028	0.006	-10000	0	-10000	0	0

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	0.045	0.05	-10000	0	-0.37	6	6
fibroblast growth factor receptor signaling pathway	0.045	0.05	-10000	0	-0.37	6	6
LAMA1	0.013	0.095	-10000	0	-0.54	14	14
PRNP	0.028	0.005	-10000	0	-10000	0	0
GPC1/SLIT2	-0.06	0.2	-10000	0	-0.45	100	100
SMAD2	0.019	0.026	-10000	0	-0.35	1	1
GPC1/PrPc/Cu2+	0.035	0.022	-10000	0	-0.39	1	1
GPC1/Laminin alpha1	0.028	0.074	-10000	0	-0.44	11	11
TDGF1	-0.38	0.26	-10000	0	-0.52	383	383
CRIPTO/GPC1	-0.27	0.2	-10000	0	-0.45	262	262
APP/GPC1	0.038	0.025	-10000	0	-0.45	1	1
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.23	0.17	-10000	0	-0.39	259	259
FLT1	0.023	0.053	-10000	0	-0.5	5	5
GPC1/TGFB/TGFBR1/TGFBR2	0.039	0.033	-10000	0	-0.39	1	1
SERPINC1	-0.027	0.18	-10000	0	-0.6	44	44
FYN	-0.23	0.18	-10000	0	-0.39	261	261
FGR	-0.23	0.18	-10000	0	-0.39	262	262
positive regulation of MAPKKK cascade	-0.27	0.19	0.38	3	-0.42	267	270
SLIT2	-0.1	0.26	-10000	0	-0.59	108	108
GPC1/NRG	0.023	0.08	-10000	0	-0.45	13	13
NRG1	0.009	0.1	-10000	0	-0.53	16	16
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.11	0.18	-10000	0	-0.31	222	222
LYN	-0.22	0.17	-10000	0	-0.39	253	253
mol:Spermine	0.009	0.021	-10000	0	-0.45	1	1
cell growth	0.045	0.05	-10000	0	-0.37	6	6
BMP signaling pathway	-0.026	0.029	0.61	1	-10000	0	1
SRC	-0.23	0.17	-10000	0	-0.39	254	254
TGFBR1	0.028	0.006	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.02	0.15	-10000	0	-0.5	43	43
GPC1	0.026	0.029	-10000	0	-0.61	1	1
TGFBR1 (dimer)	0.028	0.006	-10000	0	-10000	0	0
VEGFA	-0.21	0.26	-10000	0	-0.5	228	228
BLK	-0.24	0.2	-10000	0	-0.41	266	266
HCK	-0.24	0.18	-10000	0	-0.4	266	266
FGF2	0.022	0.061	-10000	0	-0.59	5	5
FGFR1	0.026	0.008	-10000	0	-10000	0	0
VEGFR1 homodimer	0.023	0.053	-10000	0	-0.5	5	5
TGFBR2	0.021	0.013	-10000	0	-10000	0	0
cell death	0.038	0.025	-10000	0	-0.45	1	1
ATIII/GPC1	-0.004	0.14	-10000	0	-0.44	45	45
PLA2G2A/GPC1	0.002	0.11	-10000	0	-0.36	44	44
LCK	-0.24	0.18	-10000	0	-0.4	270	270
neuron differentiation	0.023	0.08	-10000	0	-0.44	13	13
PrPc/Cu2+	0.021	0.004	-10000	0	-10000	0	0
APP	0.028	0.006	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.021	0.013	-10000	0	-10000	0	0

Aurora B signaling

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
Condensin I complex	-0.1	0.16	-10000	0	-0.39	87	87
STMN1	-0.15	0.19	-10000	0	-0.36	239	239
Aurora B/RasGAP/Survivin	-0.18	0.26	-10000	0	-0.45	227	227
Chromosomal passenger complex/Cul3 protein complex	-0.075	0.13	-10000	0	-0.4	34	34
BIRC5	-0.13	0.25	-10000	0	-0.52	148	148
DES	-0.23	0.29	-10000	0	-0.63	157	157
Aurora C/Aurora B/INCENP	-0.096	0.17	-10000	0	-0.27	234	234
Aurora B/TACC1	-0.12	0.17	-10000	0	-0.3	236	236
Aurora B/PP2A	-0.14	0.2	-10000	0	-0.36	238	238
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	-0.028	0.049	-10000	0	-0.2	3	3
mitotic metaphase/anaphase transition	0.001	0.005	-10000	0	-10000	0	0
NDC80	-0.22	0.27	-10000	0	-0.48	241	241
Cul3 protein complex	0.04	0.077	-10000	0	-0.39	15	15
KIF2C	-0.066	0.13	-10000	0	-0.38	42	42
PEBP1	0.023	0.01	-10000	0	-10000	0	0
KIF20A	-0.16	0.25	-10000	0	-0.5	174	174
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	-0.13	0.19	-10000	0	-0.36	213	213
SEPT1	-0.041	0.18	-10000	0	-0.5	66	66
SMC2	0.028	0.006	-10000	0	-10000	0	0
SMC4	0.027	0.006	-10000	0	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.034	0.15	0.28	1	-0.7	11	12
PSMA3	0.027	0.008	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.004	-10000	0	-10000	0	0
H3F3B	-0.079	0.11	-10000	0	-0.2	231	231
AURKB	-0.22	0.27	-10000	0	-0.51	239	239
AURKC	0.026	0.033	-10000	0	-0.5	2	2
CDCA8	-0.002	0.1	-10000	0	-0.53	19	19
cytokinesis	-0.13	0.18	-10000	0	-0.42	94	94
Aurora B/Septin1	-0.14	0.23	-10000	0	-0.53	82	82
AURKA	0.023	0.053	-10000	0	-0.51	5	5
INCENP	0.018	0.019	-10000	0	-10000	0	0
KLHL13	0.009	0.11	-10000	0	-0.59	16	16
BUB1	-0.2	0.26	-10000	0	-0.51	220	220
hSgo1/Aurora B/Survivin	-0.19	0.26	-10000	0	-0.44	227	227
EVI5	0.027	0.006	-10000	0	-10000	0	0
RhoA/GTP	-0.11	0.18	-10000	0	-0.4	83	83
SGOL1	0.001	0.1	-10000	0	-0.52	18	18
CENPA	-0.12	0.16	0.19	1	-0.32	158	159
NCAPG	-0.15	0.25	-10000	0	-0.5	171	171
Aurora B/HC8 Proteasome	-0.14	0.2	-10000	0	-0.35	238	238
NCAPD2	0.028	0.006	-10000	0	-10000	0	0
Aurora B/PP1-gamma	-0.14	0.2	-10000	0	-0.36	229	229
RHOA	0.021	0.013	-10000	0	-10000	0	0
NCAPH	-0.06	0.2	-10000	0	-0.5	84	84
NPM1	-0.072	0.11	-10000	0	-0.52	7	7
RASA1	0.024	0.03	-10000	0	-0.61	1	1
KLHL9	0.028	0.006	-10000	0	-10000	0	0
mitotic prometaphase	-0.005	0.007	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.14	0.2	-10000	0	-0.35	238	238
PPP1CC	0.028	0.005	-10000	0	-10000	0	0
Centraspindlin	-0.11	0.2	-10000	0	-0.43	92	92
RhoA/GDP	0.015	0.01	-10000	0	-10000	0	0
NSUN2	-0.076	0.12	-10000	0	-0.55	6	6
MYLK	-0.085	0.12	-10000	0	-0.38	15	15
KIF23	0.018	0.067	-10000	0	-0.51	8	8
VIM	-0.18	0.22	-10000	0	-0.4	250	250
RACGAP1	0.025	0.025	-10000	0	-0.52	1	1
mitosis	0	0	-10000	0	-10000	0	0
NCL	-0.09	0.15	-10000	0	-0.6	18	18
Chromosomal passenger complex	-0.13	0.19	0.18	1	-0.37	164	165
Chromosomal passenger complex/EVI5	-0.14	0.27	-10000	0	-0.52	144	144
TACC1	0.026	0.008	-10000	0	-10000	0	0
PPP2R5D	0.028	0.006	-10000	0	-10000	0	0
CUL3	0.027	0.006	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

IL12-mediated signaling events

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
IL12/IL12R/TYK2/JAK2/SOCS1	-0.097	0.15	-10000	0	-0.4	58	58
TBX21	-0.35	0.46	0.74	1	-0.96	146	147
B2M	0.021	0.015	-10000	0	-10000	0	0
TYK2	0.002	0.037	-10000	0	-10000	0	0
IL12RB1	-0.16	0.26	-10000	0	-0.54	158	158
GADD45B	-0.19	0.3	0.57	1	-0.69	52	53
IL12RB2	-0.074	0.19	-10000	0	-0.52	74	74
GADD45G	-0.21	0.31	0.57	1	-0.68	70	71
natural killer cell activation	-0.011	0.025	-10000	0	-10000	0	0
RELB	0.029	0.003	-10000	0	-10000	0	0
RELA	0.029	0.003	-10000	0	-10000	0	0
IL18	0.021	0.053	-10000	0	-0.5	5	5
IL2RA	-0.076	0.21	-10000	0	-0.5	100	100
IFNG	-0.21	0.26	-10000	0	-0.5	230	230
STAT3 (dimer)	-0.26	0.35	-10000	0	-0.7	156	156
HLA-DRB5	-0.005	0.13	-10000	0	-0.5	31	31
FASLG	-0.38	0.47	0.74	1	-0.96	163	164
NF kappa B2 p52/RelB	-0.29	0.41	-10000	0	-0.83	151	151
CD4	0.018	0.071	-10000	0	-0.5	9	9
SOCS1	0.021	0.058	-10000	0	-0.5	6	6
EntrezGene:6955	-0.004	0.009	-10000	0	-10000	0	0
CD3D	-0.22	0.27	-10000	0	-0.51	228	228
CD3E	-0.19	0.26	-10000	0	-0.51	204	204
CD3G	-0.19	0.27	-10000	0	-0.52	200	200
IL12Rbeta2/JAK2	-0.052	0.15	-10000	0	-0.38	74	74
CCL3	-0.32	0.44	0.74	1	-0.91	139	140
CCL4	-0.33	0.45	0.74	1	-0.97	134	135
HLA-A	0.019	0.036	-10000	0	-0.51	2	2
IL18/IL18R	-0.053	0.18	-10000	0	-0.34	105	105
NOS2	-0.25	0.33	-10000	0	-0.74	100	100
IL12/IL12R/TYK2/JAK2/SPHK2	-0.095	0.15	-10000	0	-0.39	57	57
IL1R1	-0.3	0.41	0.74	1	-0.89	120	121
IL4	0.017	0.036	-10000	0	-10000	0	0
JAK2	0.001	0.036	-10000	0	-10000	0	0
EntrezGene:6957	-0.004	0.009	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.32	0.38	-10000	0	-0.73	216	216
RAB7A	-0.16	0.28	0.54	4	-0.65	18	22
lysosomal transport	-0.15	0.27	0.52	5	-0.62	18	23
FOS	-0.25	0.36	-10000	0	-0.71	140	140
STAT4 (dimer)	-0.26	0.38	0.56	5	-0.77	132	137
STAT5A (dimer)	-0.38	0.47	-10000	0	-0.9	200	200
GZMA	-0.36	0.46	-10000	0	-0.97	148	148
GZMB	-0.35	0.45	-10000	0	-0.93	156	156
HLX	-0.033	0.17	-10000	0	-0.51	58	58
LCK	-0.33	0.44	0.52	1	-0.91	155	156
TCR/CD3/MHC II/CD4	-0.18	0.23	-10000	0	-0.44	206	206
IL2/IL2R	-0.19	0.25	-10000	0	-0.6	88	88
MAPK14	-0.19	0.32	0.58	1	-0.68	70	71
CCR5	-0.35	0.4	0.57	1	-0.84	158	159
IL1B	-0.005	0.068	-10000	0	-0.54	6	6
STAT6	-0.07	0.11	-10000	0	-10000	0	0
STAT4	-0.003	0.12	-10000	0	-0.5	29	29
STAT3	0.028	0.004	-10000	0	-10000	0	0
STAT1	0.026	0.024	-10000	0	-0.5	1	1
NFKB1	0.027	0.029	-10000	0	-0.61	1	1
NFKB2	0.028	0.006	-10000	0	-10000	0	0
IL12B	-0.053	0.16	-10000	0	-0.53	52	52
CD8A	-0.22	0.27	-10000	0	-0.52	230	230
CD8B	-0.17	0.26	-10000	0	-0.52	184	184
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.097	0.15	0.39	58	-10000	0	58
IL2RB	-0.25	0.27	-10000	0	-0.5	270	270
proteasomal ubiquitin-dependent protein catabolic process	-0.23	0.36	0.53	6	-0.7	131	137
IL2RG	-0.007	0.13	-10000	0	-0.51	34	34
IL12	-0.038	0.13	-10000	0	-0.4	52	52
STAT5A	0.028	0.004	-10000	0	-10000	0	0
CD247	-0.15	0.25	-10000	0	-0.51	166	166
IL2	0.014	0.073	-10000	0	-0.5	10	10
SPHK2	0.026	0.04	-10000	0	-0.61	2	2
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.001	0.036	-10000	0	-10000	0	0
IL12/IL12R/TYK2/JAK2	-0.35	0.45	-10000	0	-0.94	155	155
MAP2K3	-0.2	0.32	0.57	1	-0.66	90	91
RIPK2	0.026	0.024	-10000	0	-0.5	1	1
MAP2K6	-0.2	0.32	0.57	1	-0.68	80	81
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.023	0.048	-10000	0	-0.5	4	4
IL18RAP	-0.11	0.24	-10000	0	-0.51	132	132
IL12Rbeta1/TYK2	-0.11	0.21	-10000	0	-0.41	158	158
EOMES	-0.28	0.29	-10000	0	-0.82	69	69
STAT1 (dimer)	-0.3	0.37	-10000	0	-0.75	159	159
T cell proliferation	-0.19	0.28	0.45	5	-0.58	102	107
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.018	0.068	-10000	0	-0.55	7	7
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.24	0.28	-10000	0	-0.65	95	95
ATF2	-0.18	0.31	0.53	7	-0.65	64	71

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.034	0.17	-10000	0	-0.36	99	99
alphaM/beta2 Integrin/GPIbA	-0.033	0.17	-10000	0	-0.36	97	97
alphaM/beta2 Integrin/proMMP-9	-0.18	0.25	-10000	0	-0.4	250	250
PLAUR	0.003	0.11	-10000	0	-0.5	24	24
HMGB1	0.023	0.022	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.033	0.17	-10000	0	-0.36	96	96
AGER	-0.071	0.2	-10000	0	-0.51	90	90
RAP1A	0.028	0.005	-10000	0	-10000	0	0
SELPLG	-0.005	0.13	-10000	0	-0.5	32	32
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.081	0.21	-10000	0	-0.5	61	61
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	-0.21	0.26	-10000	0	-0.5	230	230
CYR61	0.022	0.055	-10000	0	-0.46	6	6
TLN1	0.028	0.006	-10000	0	-10000	0	0
Rap1/GTP	-0.18	0.15	-10000	0	-0.4	105	105
RHOA	0.021	0.013	-10000	0	-10000	0	0
P-selectin oligomer	0.002	0.12	-10000	0	-0.61	20	20
MYH2	-0.27	0.18	-10000	0	-0.47	173	173
MST1R	0.013	0.067	-10000	0	-0.54	7	7
leukocyte activation during inflammatory response	-0.12	0.2	-10000	0	-0.46	82	82
APOB	-0.15	0.25	-10000	0	-0.51	166	166
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	0.022	0.055	-10000	0	-0.52	5	5
JAM3	0.029	0.003	-10000	0	-10000	0	0
GP1BA	0.027	0.029	-10000	0	-0.61	1	1
alphaM/beta2 Integrin/CTGF	-0.039	0.17	-10000	0	-0.36	101	101
alphaM/beta2 Integrin	-0.21	0.17	-10000	0	-0.37	215	215
JAM3 homodimer	0.029	0.003	-10000	0	-10000	0	0
ICAM2	0.028	0.005	-10000	0	-10000	0	0
ICAM1	0.017	0.077	-10000	0	-0.5	11	11
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.21	0.17	-10000	0	-0.36	215	215
cell adhesion	-0.033	0.17	-10000	0	-0.36	97	97
NFKB1	-0.097	0.22	0.39	5	-0.54	62	67
THY1	0.027	0.028	-10000	0	-0.61	1	1
RhoA/GDP	0.015	0.01	-10000	0	-10000	0	0
Lipoprotein(a)	-0.083	0.17	-10000	0	-0.32	166	166
alphaM/beta2 Integrin/LRP/tPA	-0.021	0.16	-10000	0	-0.44	37	37
IL6	-0.12	0.27	0.38	3	-0.64	76	79
ITGB2	-0.077	0.21	-10000	0	-0.5	96	96
elevation of cytosolic calcium ion concentration	-0.033	0.18	-10000	0	-0.47	42	42
alphaM/beta2 Integrin/JAM2/JAM3	-0.012	0.16	-10000	0	-0.45	28	28
JAM2	0.028	0.006	-10000	0	-10000	0	0
alphaM/beta2 Integrin/ICAM1	-0.033	0.16	-10000	0	-0.48	30	30
alphaM/beta2 Integrin/uPA/Plg	-0.21	0.25	-10000	0	-0.43	252	252
RhoA/GTP	-0.28	0.2	-10000	0	-0.48	184	184
positive regulation of phagocytosis	-0.17	0.17	-10000	0	-0.47	82	82
Ron/MSP	0.018	0.074	-10000	0	-0.4	14	14
alphaM/beta2 Integrin/uPAR/uPA	-0.031	0.18	-10000	0	-0.47	42	42
alphaM/beta2 Integrin/uPAR	-0.045	0.19	-10000	0	-0.37	109	109
PLAU	0.019	0.072	-10000	0	-0.53	8	8
PLAT	0.015	0.085	-10000	0	-0.58	10	10
actin filament polymerization	-0.26	0.17	-10000	0	-0.45	172	172
MST1	0.012	0.07	-10000	0	-0.53	8	8
alphaM/beta2 Integrin/lipoprotein(a)	-0.12	0.21	-10000	0	-0.46	82	82
TNF	-0.093	0.22	0.39	4	-0.52	63	67
RAP1B	0.028	0.005	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.038	0.17	-10000	0	-0.36	102	102
fibrinolysis	-0.21	0.24	-10000	0	-0.42	252	252
HCK	0.001	0.12	-10000	0	-0.5	26	26
dendritic cell antigen processing and presentation	-0.21	0.17	-10000	0	-0.36	215	215
VTN	-0.065	0.22	-10000	0	-0.59	76	76
alphaM/beta2 Integrin/CYR61	-0.035	0.17	-10000	0	-0.36	99	99
LPA	0.018	0.044	-10000	0	-0.54	3	3
LRP1	0.028	0.005	-10000	0	-10000	0	0
cell migration	-0.16	0.23	-10000	0	-0.45	135	135
FN1	-0.012	0.14	-10000	0	-0.51	37	37
alphaM/beta2 Integrin/Thy1	-0.033	0.17	-10000	0	-0.36	97	97
MPO	0.01	0.096	-10000	0	-0.5	17	17
KNG1	-0.43	0.28	-10000	0	-0.6	370	370
RAP1/GDP	0.037	0.01	-10000	0	-10000	0	0
ROCK1	-0.26	0.18	-10000	0	-0.46	170	170
ELA2	0	0	-10000	0	-10000	0	0
PLG	-0.29	0.31	-10000	0	-0.58	265	265
CTGF	0.018	0.075	-10000	0	-0.61	7	7
alphaM/beta2 Integrin/Hck	-0.046	0.2	-10000	0	-0.42	98	98
ITGAM	0.003	0.1	-10000	0	-0.5	19	19
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.041	0.2	-10000	0	-0.49	61	61
HP	-0.1	0.23	-10000	0	-0.51	124	124
leukocyte adhesion	-0.058	0.17	-10000	0	-0.44	41	41
SELP	0.002	0.12	-10000	0	-0.61	20	20

BMP receptor signaling

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
BMP7/BMPR2/BMPR1A-1B/FS	-0.44	0.26	-10000	0	-0.54	413	413
SMAD6-7/SMURF1	0.051	0.02	-10000	0	-10000	0	0
NOG	-0.06	0.2	-10000	0	-0.52	81	81
SMAD9	-0.067	0.17	-10000	0	-0.62	38	38
SMAD4	0.028	0.005	-10000	0	-10000	0	0
SMAD5	-0.14	0.16	-10000	0	-0.47	32	32
BMP7/USAG1	-0.5	0.3	-10000	0	-0.62	416	416
SMAD5/SKI	-0.14	0.16	0.31	3	-0.47	29	32
SMAD1	-0.026	0.056	-10000	0	-10000	0	0
BMP2	0.024	0.049	-10000	0	-0.61	3	3
SMAD1/SMAD1/SMAD4	0.005	0.058	-10000	0	-10000	0	0
BMPR1A	0.028	0.006	-10000	0	-10000	0	0
BMPR1B	-0.41	0.3	-10000	0	-0.61	350	350
BMPR1A-1B/BAMBI	-0.25	0.21	-10000	0	-0.39	344	344
AHSG	0.011	0.078	-10000	0	-0.51	11	11
CER1	0.02	0.006	-10000	0	-10000	0	0
BMP2-4/CER1	0.042	0.045	-10000	0	-0.4	4	4
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.1	0.12	-10000	0	-0.44	10	10
BMP2-4 (homodimer)	0.034	0.048	-10000	0	-0.45	4	4
RGMB	0.023	0.035	-10000	0	-0.5	2	2
BMP6/BMPR2/BMPR1A-1B	-0.22	0.19	-10000	0	-0.36	334	334
RGMA	0.022	0.063	-10000	0	-0.61	5	5
SMURF1	0.026	0.009	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.12	0.13	-10000	0	-0.35	47	47
BMP2-4/USAG1	-0.21	0.22	-10000	0	-0.39	292	292
SMAD6/SMURF1/SMAD5	-0.14	0.15	0.3	1	-0.48	26	27
SOSTDC1	-0.34	0.31	-10000	0	-0.61	293	293
BMP7/BMPR2/BMPR1A-1B	-0.44	0.26	-10000	0	-0.54	417	417
SKI	0.028	0.006	-10000	0	-10000	0	0
BMP6 (homodimer)	0.018	0.076	-10000	0	-0.57	8	8
HFE2	0.007	0.099	-10000	0	-0.51	18	18
ZFYVE16	0.026	0.009	-10000	0	-10000	0	0
MAP3K7	0.027	0.007	-10000	0	-10000	0	0
BMP2-4/CHRD	0.042	0.069	-10000	0	-0.4	10	10
SMAD5/SMAD5/SMAD4	-0.15	0.16	0.29	2	-0.48	29	31
MAPK1	0.028	0.004	-10000	0	-10000	0	0
TAK1/TAB family	-0.1	0.12	-10000	0	-0.42	8	8
BMP7 (homodimer)	-0.39	0.3	-10000	0	-0.61	332	332
NUP214	0.028	0.005	-10000	0	-10000	0	0
BMP6/FETUA	0.021	0.077	-10000	0	-0.39	15	15
SMAD1/SKI	-0.023	0.068	0.34	1	-0.44	1	2
SMAD6	0.029	0.003	-10000	0	-10000	0	0
CTDSP2	0.028	0.005	-10000	0	-10000	0	0
BMP2-4/FETUA	0.037	0.066	-10000	0	-0.33	14	14
MAP3K7IP1	0	0	-10000	0	-10000	0	0
GREM1	-0.13	0.27	-10000	0	-0.6	126	126
BMPR2 (homodimer)	0.027	0.006	-10000	0	-10000	0	0
GADD34/PP1CA	0.052	0.019	-10000	0	-10000	0	0
BMPR1A-1B (homodimer)	-0.3	0.23	-10000	0	-0.45	344	344
CHRDL1	-0.3	0.32	-10000	0	-0.61	265	265
ENDOFIN/SMAD1	-0.02	0.065	0.34	1	-0.45	1	2
SMAD6-7/SMURF1/SMAD1	0.008	0.068	-10000	0	-0.42	1	1
SMAD6/SMURF1	0.026	0.009	-10000	0	-10000	0	0
BAMBI	0.021	0.065	-10000	0	-0.56	6	6
SMURF2	0.027	0.029	-10000	0	-0.61	1	1
BMP2-4/CHRDL1	-0.18	0.22	-10000	0	-0.39	258	258
BMP2-4/GREM1	-0.056	0.19	-10000	0	-0.38	124	124
SMAD7	0.028	0.005	-10000	0	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.065	0.17	-10000	0	-0.57	46	46
SMAD1/SMAD6	-0.022	0.063	-10000	0	-0.45	1	1
TAK1/SMAD6	0.036	0.016	-10000	0	-10000	0	0
BMP7	-0.39	0.3	-10000	0	-0.61	332	332
BMP6	0.018	0.076	-10000	0	-0.57	8	8
MAP3K7IP2	0	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.098	0.11	-10000	0	-0.34	27	27
PPM1A	0.027	0.008	-10000	0	-10000	0	0
SMAD1/SMURF2	-0.024	0.069	0.34	1	-0.45	1	2
SMAD7/SMURF1	0.037	0.014	-10000	0	-10000	0	0
CTDSPL	0.02	0.013	-10000	0	-10000	0	0
PPP1CA	0.029	0.003	-10000	0	-10000	0	0
XIAP	0.029	0.003	-10000	0	-10000	0	0
CTDSP1	0.027	0.007	-10000	0	-10000	0	0
PPP1R15A	0.029	0.003	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.16	0.17	-10000	0	-0.46	75	75
CHRD	0.017	0.08	-10000	0	-0.57	9	9
BMPR2	0.027	0.006	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.13	0.13	-10000	0	-0.36	48	48
BMP4	0.023	0.049	-10000	0	-0.61	3	3
FST	-0.037	0.19	-10000	0	-0.59	52	52
BMP2-4/NOG	-0.01	0.14	-10000	0	-0.33	79	79
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.4	0.25	-10000	0	-0.51	396	396

Aurora C 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.029	0.003	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.1	0.17	-9999	-0.28	234	234
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.024	0.051	-9999	-0.57	1	1
AURKB	-0.22	0.27	-9999	-0.51	239	239
AURKC	0.026	0.033	-9999	-0.5	2	2

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.011	0.14	-9999	-0.51	38	38
GPC2	-0.029	0.16	-9999	-0.5	52	52
GPC2/Midkine	-0.03	0.16	-9999	-0.41	77	77
neuron projection morphogenesis	-0.03	0.16	-9999	-0.4	77	77

FOXM1 transcription factor network

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
NFATC3	-0.11	0.48	0.75	1	-1	61	62
PLK1	-0.039	0.22	-10000	0	-1.5	1	1
BIRC5	-0.063	0.24	-10000	0	-0.74	9	9
HSPA1B	-0.11	0.48	0.75	2	-1.1	59	61
MAP2K1	0.024	0.051	-10000	0	-10000	0	0
BRCA2	-0.12	0.48	-10000	0	-1.1	63	63
FOXM1	-0.16	0.59	-10000	0	-1.3	77	77
XRCC1	-0.11	0.48	-10000	0	-1	71	71
FOXM1B/p19	-0.23	0.45	-10000	0	-1.1	72	72
Cyclin D1/CDK4	-0.11	0.45	-10000	0	-0.96	61	61
CDC2	-0.12	0.5	-10000	0	-1.1	77	77
TGFA	-0.11	0.44	-10000	0	-0.94	61	61
SKP2	-0.099	0.48	0.68	5	-1	68	73
CCNE1	0.023	0.06	-10000	0	-0.52	6	6
CKS1B	-0.11	0.48	0.67	1	-1	65	66
RB1	-0.023	0.27	-10000	0	-0.89	12	12
FOXM1C/SP1	-0.14	0.53	-10000	0	-1.1	78	78
AURKB	-0.13	0.28	-10000	0	-1.2	9	9
CENPF	-0.13	0.52	0.67	1	-1.1	69	70
CDK4	0.024	0.025	-10000	0	-10000	0	0
MYC	-0.097	0.43	-10000	0	-0.91	68	68
CHEK2	0.023	0.057	-10000	0	-0.56	1	1
ONECUT1	-0.12	0.47	-10000	0	-1	71	71
CDKN2A	-0.48	0.11	-10000	0	-0.5	489	489
LAMA4	-0.16	0.49	0.75	1	-1.1	72	73
FOXM1B/HNF6	-0.15	0.54	-10000	0	-1.2	68	68
FOS	-0.13	0.5	-10000	0	-1.1	74	74
SP1	0.028	0.009	-10000	0	-10000	0	0
CDC25B	-0.11	0.48	-10000	0	-1	68	68
response to radiation	0.005	0.033	-10000	0	-10000	0	0
CENPB	-0.11	0.48	-10000	0	-1	68	68
CENPA	-0.17	0.54	0.66	1	-1.1	90	91
NEK2	-0.15	0.53	0.67	1	-1.1	86	87
HIST1H2BA	-0.12	0.48	0.75	1	-1	69	70
CCNA2	-0.076	0.22	-10000	0	-0.52	100	100
EP300	0.027	0.029	-10000	0	-0.61	1	1
CCNB1/CDK1	-0.14	0.54	-10000	0	-1.2	71	71
CCNB2	-0.15	0.53	0.75	1	-1.1	95	96
CCNB1	-0.12	0.51	-10000	0	-1.1	70	70
ETV5	-0.11	0.48	-10000	0	-1	71	71
ESR1	-0.12	0.48	0.75	1	-1.1	62	63
CCND1	-0.11	0.45	-10000	0	-0.98	63	63
GSK3A	0.025	0.044	-10000	0	-10000	0	0
Cyclin A-E1/CDK1-2	-0.013	0.17	-10000	0	-0.35	93	93
CDK2	0.029	0.01	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.005	0.04	-10000	0	-10000	0	0
FOXM1B/Cbp/p300	-0.13	0.51	-10000	0	-1.1	75	75
GAS1	-0.16	0.52	-10000	0	-1.1	89	89
MMP2	-0.11	0.48	0.75	1	-1	69	70
RB1/FOXM1C	-0.12	0.48	-10000	0	-1	69	69
CREBBP	0.028	0.006	-10000	0	-10000	0	0

JNK 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
LAT/GRAP2/SLP76/HPK1	-0.17	0.3	-10000	0	-0.47	214	214
MAP4K1	-0.19	0.26	-10000	0	-0.5	207	207
MAP3K8	0.026	0.033	-10000	0	-0.5	2	2
PRKCB	0.022	0.057	-10000	0	-0.55	5	5
DBNL	0.026	0.009	-10000	0	-10000	0	0
CRKL	0.028	0.004	-10000	0	-10000	0	0
MAP3K1	-0.06	0.13	-10000	0	-0.41	37	37
JUN	0.015	0.11	0.34	1	-0.58	12	13
MAP3K7	-0.062	0.13	-10000	0	-0.41	37	37
GRAP2	-0.008	0.14	-10000	0	-0.51	35	35
CRK	0.028	0.005	-10000	0	-10000	0	0
MAP2K4	-0.025	0.16	0.29	29	-0.39	36	65
LAT	-0.12	0.24	-10000	0	-0.5	141	141
LCP2	-0.009	0.12	-10000	0	-0.5	29	29
MAPK8	0.012	0.12	-10000	0	-0.6	13	13
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.066	0.14	-10000	0	-0.43	40	40
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.16	0.28	-10000	0	-0.6	117	117

Caspase cascade in apoptosis

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
TOP1	-0.062	0.15	-10000	0	-0.32	81	81
ACTA1	-0.1	0.18	-10000	0	-0.4	107	107
NUMA1	-0.063	0.15	0.23	1	-0.33	77	78
SPTAN1	-0.1	0.18	0.26	1	-0.4	107	108
LIMK1	-0.083	0.19	0.33	2	-0.4	100	102
BIRC3	-0.054	0.19	-10000	0	-0.5	79	79
BIRC2	0.028	0.004	-10000	0	-10000	0	0
BAX	0.029	0.003	-10000	0	-10000	0	0
CASP10	-0.16	0.24	-10000	0	-0.46	181	181
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.028	0.003	-10000	0	-10000	0	0
PTK2	-0.066	0.15	0.23	1	-0.33	82	83
DIABLO	0.028	0.005	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.098	0.18	0.26	1	-0.4	107	108
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.028	0.005	-10000	0	-10000	0	0
GSN	-0.1	0.18	0.26	1	-0.4	107	108
MADD	0.029	0.003	-10000	0	-10000	0	0
TFAP2A	-0.29	0.29	-10000	0	-0.52	287	287
BID	-0.064	0.11	-10000	0	-0.25	108	108
MAP3K1	-0.025	0.068	-10000	0	-0.25	1	1
TRADD	0.028	0.006	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.04	0.012	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.094	0.18	0.3	3	-0.4	106	109
CASP9	0.028	0.006	-10000	0	-10000	0	0
DNA repair	0.015	0.077	0.3	13	-0.18	2	15
neuron apoptosis	0.005	0.12	-10000	0	-0.62	14	14
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.084	0.18	-10000	0	-0.4	84	84
APAF1	0.028	0.005	-10000	0	-10000	0	0
CASP6	-0.023	0.14	0.36	2	-0.9	7	9
TRAF2	0.028	0.005	-10000	0	-10000	0	0
ICAD/CAD	-0.095	0.17	0.4	1	-0.41	81	82
CASP7	0.027	0.1	-10000	0	-0.33	8	8
KRT18	0.012	0.038	-10000	0	-10000	0	0
apoptosis	-0.094	0.18	0.42	2	-0.4	91	93
DFFA	-0.099	0.18	-10000	0	-0.4	107	107
DFFB	-0.099	0.18	-10000	0	-0.4	107	107
PARP1	-0.015	0.078	0.18	2	-0.3	13	15
actin filament polymerization	0.073	0.18	0.4	72	-0.4	2	74
TNF	0.018	0.073	-10000	0	-0.56	8	8
CYCS	-0.04	0.095	0.18	6	-0.19	97	103
SATB1	-0.022	0.14	0.43	2	-0.83	7	9
SLK	-0.099	0.18	0.34	1	-0.4	108	109
p15 BID/BAX	-0.043	0.11	-10000	0	-0.25	2	2
CASP2	0.024	0.08	0.22	36	-0.44	2	38
JNK cascade	0.024	0.068	0.25	1	-10000	0	1
CASP3	-0.11	0.19	-10000	0	-0.42	107	107
LMNB2	0.025	0.11	0.36	11	-0.54	6	17
RIPK1	0.028	0.005	-10000	0	-10000	0	0
CASP4	0.028	0.003	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	0.018	0.12	-10000	0	-0.28	75	75
negative regulation of DNA binding	-0.28	0.29	-10000	0	-0.52	287	287
stress fiber formation	-0.099	0.18	0.34	1	-0.4	108	109
GZMB	-0.18	0.28	-10000	0	-0.53	185	185
CASP1	0.019	0.002	-10000	0	-10000	0	0
LMNB1	0.02	0.099	0.37	9	-0.42	6	15
APP	0.004	0.12	-10000	0	-0.63	14	14
TNFRSF1A	0.028	0.006	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.01	0.002	-10000	0	-10000	0	0
VIM	-0.092	0.17	0.29	1	-0.39	90	91
LMNA	0.023	0.11	0.36	11	-0.38	11	22
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.014	0.059	-10000	0	-0.47	2	2
LRDD	0	0	-10000	0	-10000	0	0
SREBF1	-0.099	0.18	0.3	1	-0.4	107	108
APAF-1/Caspase 9	-0.014	0.13	-10000	0	-0.59	22	22
nuclear fragmentation during apoptosis	-0.062	0.15	0.23	1	-0.33	77	78
CFL2	-0.077	0.18	0.4	2	-0.4	72	74
GAS2	-0.11	0.18	0.39	1	-0.4	116	117
positive regulation of apoptosis	0.027	0.11	0.36	11	-0.46	7	18
PRF1	-0.11	0.23	-10000	0	-0.5	131	131

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	0.013	0.097	-10000	0	-0.59	13	13
oxygen homeostasis	0	0	-10000	0	-10000	0	0
TCEB2	0.024	0.044	-10000	0	-0.54	3	3
TCEB1	0.027	0.007	-10000	0	-10000	0	0
HIF1A/p53	-0.061	0.077	0.26	1	-0.44	15	16
HIF1A	-0.067	0.078	-10000	0	-0.46	15	15
COPS5	0.027	0.007	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.053	0.05	-10000	0	-0.33	1	1
FIH (dimer)	0.028	0.006	-10000	0	-10000	0	0
CDKN2A	-0.49	0.11	-10000	0	-0.51	489	489
ARNT/IPAS	0.028	0.075	-10000	0	-0.43	13	13
HIF1AN	0.028	0.006	-10000	0	-10000	0	0
GNB2L1	0.022	0.012	-10000	0	-10000	0	0
HIF1A/ARNT	-0.06	0.079	0.26	1	-0.44	15	16
CUL2	0.028	0.004	-10000	0	-10000	0	0
OS9	0.028	0.005	-10000	0	-10000	0	0
RACK1/Elongin B/Elongin C	0.039	0.039	-10000	0	-0.33	3	3
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF1A/Hsp90	-0.053	0.077	-10000	0	-0.44	15	15
PHD1-3/OS9	-0.23	0.11	-10000	0	-0.36	21	21
HIF1A/RACK1/Elongin B/Elongin C	-0.041	0.078	-10000	0	-0.42	14	14
VHL	0.02	0.019	-10000	0	-0.3	1	1
HSP90AA1	0.027	0.008	-10000	0	-10000	0	0
HIF1A/JAB1	-0.058	0.078	-10000	0	-0.44	15	15
EGLN3	-0.45	0.17	-10000	0	-0.51	451	451
EGLN2	0.029	0.003	-10000	0	-10000	0	0
EGLN1	0.028	0.006	-10000	0	-10000	0	0
TP53	0.028	0.005	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	-0.13	0.26	-10000	0	-0.52	149	149
ARNT	0.027	0.006	-10000	0	-10000	0	0
ARD1A	0	0	-10000	0	-10000	0	0
RBX1	0.028	0.004	-10000	0	-10000	0	0
HIF1A/p19ARF	-0.3	0.095	-10000	0	-0.32	435	435

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.42	0.39	-10000	0	-1.1	69	69
STAT6 (cleaved dimer)	-0.46	0.41	-10000	0	-1.1	110	110
IGHG1	-0.15	0.15	-10000	0	-0.44	10	10
IGHG3	-0.41	0.38	-10000	0	-0.99	93	93
AKT1	-0.22	0.24	-10000	0	-0.68	41	41
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.17	0.19	-10000	0	-0.62	23	23
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.23	0.24	-10000	0	-0.74	35	35
THY1	-0.42	0.4	-10000	0	-1.1	74	74
MYB	-0.12	0.24	-10000	0	-0.51	139	139
HMGA1	0.027	0.024	-10000	0	-0.5	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.3	0.28	-10000	0	-0.75	81	81
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.23	0.24	-10000	0	-0.73	35	35
SP1	0.024	0.03	-10000	0	-10000	0	0
INPP5D	0.023	0.047	-10000	0	-0.5	4	4
SOCS5	0.039	0.02	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.44	0.41	-10000	0	-1.1	99	99
SOCS1	-0.3	0.28	-10000	0	-0.75	54	54
SOCS3	-0.25	0.24	-10000	0	-0.72	34	34
FCER2	-0.36	0.34	-10000	0	-0.96	63	63
PARP14	0.027	0.008	-10000	0	-10000	0	0
CCL17	-0.43	0.4	-10000	0	-1.1	72	72
GRB2	0.028	0.005	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.19	0.21	-10000	0	-0.64	36	36
T cell proliferation	-0.43	0.41	-10000	0	-1.1	83	83
IL4R/JAK1	-0.42	0.39	-10000	0	-1	83	83
EGR2	-0.44	0.41	-10000	0	-1.1	79	79
JAK2	-0.022	0.038	-10000	0	-10000	0	0
JAK3	-0.079	0.22	-10000	0	-0.51	103	103
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
JAK1	0.006	0.02	-10000	0	-10000	0	0
COL1A2	-0.16	0.18	-10000	0	-0.62	24	24
CCL26	-0.41	0.4	-10000	0	-1.1	70	70
IL4R	-0.44	0.42	-10000	0	-1.1	81	81
PTPN6	0.039	0.014	-10000	0	-10000	0	0
IL13RA2	-0.49	0.48	-10000	0	-1.3	98	98
IL13RA1	-0.022	0.04	-10000	0	-10000	0	0
IRF4	-0.17	0.24	-10000	0	-0.66	53	53
ARG1	-0.14	0.17	-10000	0	-0.74	8	8
CBL	-0.28	0.27	-10000	0	-0.72	76	76
GTF3A	-0.001	0.045	-10000	0	-10000	0	0
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
IL13RA1/JAK2	-0.027	0.053	-10000	0	-10000	0	0
IRF4/BCL6	-0.15	0.23	-10000	0	-0.63	43	43
CD40LG	-0.037	0.17	-10000	0	-0.55	51	51
MAPK14	-0.28	0.27	-10000	0	-0.72	71	71
mitosis	-0.22	0.23	-10000	0	-0.65	41	41
STAT6	-0.48	0.44	-10000	0	-1.2	90	90
SPI1	-0.042	0.18	-10000	0	-0.5	70	70
RPS6KB1	-0.2	0.23	-10000	0	-0.65	30	30
STAT6 (dimer)	-0.48	0.45	-10000	0	-1.2	90	90
STAT6 (dimer)/PARP14	-0.44	0.42	-10000	0	-1.1	91	91
mast cell activation	0.012	0.011	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.23	0.24	-10000	0	-0.67	49	49
FRAP1	-0.22	0.24	-10000	0	-0.68	41	41
LTA	-0.48	0.42	-10000	0	-1.1	90	90
FES	0.026	0.04	-10000	0	-0.61	2	2
T-helper 1 cell differentiation	0.47	0.44	1.1	90	-10000	0	90
CCL11	-0.63	0.56	-10000	0	-1.3	195	195
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.22	0.23	-10000	0	-0.66	34	34
IL2RG	-0.005	0.14	-10000	0	-0.51	34	34
IL10	-0.43	0.4	-10000	0	-1.2	48	48
IRS1	0.022	0.057	-10000	0	-0.61	4	4
IRS2	0.02	0.068	-10000	0	-0.52	8	8
IL4	-0.11	0.13	-10000	0	-1.1	3	3
IL5	-0.39	0.41	-10000	0	-1.1	63	63
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.36	0.33	-10000	0	-0.91	53	53
COL1A1	-0.27	0.27	-10000	0	-0.66	94	94
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.42	0.4	-10000	0	-1.1	61	61
IL2R gamma/JAK3	-0.066	0.22	-10000	0	-0.46	107	107
TFF3	-0.44	0.42	-10000	0	-1.1	80	80
ALOX15	-0.43	0.4	-10000	0	-1.1	68	68
MYBL1	-0.004	0.12	-10000	0	-0.5	30	30
T-helper 2 cell differentiation	-0.38	0.35	-10000	0	-0.92	85	85
SHC1	0.027	0.006	-10000	0	-10000	0	0
CEBPB	0.021	0.069	-10000	0	-0.52	8	8
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.22	0.23	-10000	0	-0.69	37	37
mol:PI-3-4-5-P3	-0.22	0.24	-10000	0	-0.68	41	41
PI3K	-0.24	0.26	-10000	0	-0.72	42	42
DOK2	-0.007	0.13	-10000	0	-0.51	31	31
ETS1	0.039	0.019	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.18	0.21	-10000	0	-0.63	38	38
ITGB3	-0.43	0.4	-10000	0	-1.2	58	58
PIGR	-0.77	0.66	-10000	0	-1.4	247	247
IGHE	0.032	0.068	0.29	5	-0.34	1	6
MAPKKK cascade	-0.18	0.2	-10000	0	-0.61	38	38
BCL6	0.027	0.006	-10000	0	-10000	0	0
OPRM1	-0.43	0.4	-10000	0	-1.1	67	67
RETNLB	-0.43	0.4	-10000	0	-1.1	85	85
SELP	-0.45	0.44	-10000	0	-1.3	67	67
AICDA	-0.48	0.41	-10000	0	-1	114	114

Syndecan-1-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
TGFB1	0.024	0.047	-10000	0	-0.5	4	4
CCL5	-0.2	0.26	-10000	0	-0.5	217	217
SDCBP	0.027	0.007	-10000	0	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.12	0.15	0.25	4	-0.42	51	55
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	-0.11	0.14	-10000	0	-0.42	44	44
Syndecan-1/Syntenin	-0.1	0.15	0.34	2	-0.43	42	44
MAPK3	-0.091	0.14	0.25	1	-0.46	22	23
HGF/MET	0.019	0.091	-10000	0	-0.42	20	20
TGFB1/TGF beta receptor Type II	0.024	0.047	-10000	0	-0.5	4	4
BSG	0.027	0.024	-10000	0	-0.5	1	1
keratinocyte migration	-0.1	0.14	-10000	0	-0.42	44	44
Syndecan-1/RANTES	-0.21	0.2	0.35	3	-0.42	181	184
Syndecan-1/CD147	-0.092	0.15	0.28	1	-0.49	22	23
Syndecan-1/Syntenin/PIP2	-0.1	0.14	0.26	1	-0.41	42	43
LAMA5	0.027	0.029	-10000	0	-0.61	1	1
positive regulation of cell-cell adhesion	-0.099	0.14	-10000	0	-0.4	42	42
MMP7	-0.082	0.24	-10000	0	-0.6	89	89
HGF	0.003	0.11	-10000	0	-0.54	20	20
Syndecan-1/CASK	-0.11	0.14	0.2	1	-0.4	51	52
Syndecan-1/HGF/MET	-0.099	0.16	-10000	0	-0.48	35	35
regulation of cell adhesion	-0.088	0.13	0.52	1	-0.47	18	19
HPSE	0.026	0.04	-10000	0	-0.61	2	2
positive regulation of cell migration	-0.12	0.15	0.25	4	-0.42	51	55
SDC1	-0.12	0.15	0.24	3	-0.43	51	54
Syndecan-1/Collagen	-0.12	0.15	0.25	4	-0.42	51	55
PPIB	0.029	0.003	-10000	0	-10000	0	0
MET	0.024	0.034	-10000	0	-0.5	2	2
PRKACA	0.029	0.002	-10000	0	-10000	0	0
MMP9	-0.21	0.26	-10000	0	-0.5	230	230
MAPK1	-0.09	0.14	0.26	2	-0.46	22	24
homophilic cell adhesion	-0.11	0.15	0.26	3	-0.42	51	54
MMP1	-0.081	0.22	-10000	0	-0.54	99	99

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.026	0.008	-10000	0	-10000	0	0
LAT2	-0.061	0.13	-10000	0	-0.4	39	39
AP1	-0.028	0.14	-10000	0	-0.52	10	10
mol:PIP3	-0.072	0.27	0.44	40	-0.52	81	121
IKBKB	-0.006	0.18	0.34	62	-0.29	31	93
AKT1	-0.058	0.17	0.42	13	-0.45	20	33
IKBKG	-0.007	0.18	0.32	63	-0.3	29	92
MS4A2	-0.088	0.22	-10000	0	-0.51	111	111
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
MAP3K1	-0.033	0.18	0.33	41	-0.39	13	54
mol:Ca2+	-0.044	0.22	0.39	43	-0.38	81	124
LYN	0.024	0.011	-10000	0	-10000	0	0
CBLB	-0.042	0.093	-10000	0	-0.34	9	9
SHC1	0.027	0.006	-10000	0	-10000	0	0
RasGAP/p62DOK	0.039	0.034	-10000	0	-0.32	2	2
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	0.023	0.047	-10000	0	-0.5	4	4
PLD2	-0.083	0.18	0.34	17	-0.51	20	37
PTPN13	-0.016	0.14	0.39	3	-0.69	8	11
PTPN11	0.025	0.014	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	0	0.16	0.41	33	-0.36	2	35
SYK	0.023	0.034	-10000	0	-0.47	2	2
GRB2	0.028	0.005	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.14	0.21	-10000	0	-0.52	92	92
LAT	-0.11	0.16	-10000	0	-0.39	87	87
PAK2	-0.053	0.17	0.35	21	-0.36	61	82
NFATC2	-0.03	0.068	-10000	0	-0.54	3	3
HRAS	-0.067	0.17	0.32	8	-0.38	69	77
GAB2	0.029	0.003	-10000	0	-10000	0	0
PLA2G1B	-0.21	0.38	-10000	0	-0.8	148	148
Fc epsilon R1	-0.11	0.2	-10000	0	-0.35	201	201
Antigen/IgE/Fc epsilon R1	-0.096	0.19	-10000	0	-0.32	200	200
mol:GDP	-0.084	0.18	0.25	1	-0.42	73	74
JUN	0.028	0.006	-10000	0	-10000	0	0
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.024	0.029	-10000	0	-0.61	1	1
FOS	0.012	0.096	-10000	0	-0.6	12	12
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.042	0.099	-10000	0	-0.32	17	17
CHUK	-0.008	0.18	0.33	61	-0.29	32	93
KLRG1	-0.045	0.098	-10000	0	-0.35	9	9
VAV1	-0.097	0.16	-10000	0	-0.38	93	93
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.041	0.096	-10000	0	-0.35	10	10
negative regulation of mast cell degranulation	-0.034	0.1	0.23	1	-0.4	9	10
BTK	-0.048	0.12	-10000	0	-0.37	13	13
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.055	0.14	-10000	0	-0.41	23	23
GAB2/PI3K/SHP2	-0.093	0.14	-10000	0	-0.49	21	21
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.042	0.1	-10000	0	-0.32	24	24
RAF1	-0.24	0.42	-10000	0	-0.9	148	148
Fc epsilon R1/FcgammaRIIB/SHIP	-0.12	0.24	-10000	0	-0.54	87	87
FCER1G	-0.07	0.21	-10000	0	-0.51	93	93
FCER1A	0.001	0.12	-10000	0	-0.6	19	19
Antigen/IgE/Fc epsilon R1/Fyn	-0.083	0.18	-10000	0	-0.47	30	30
MAPK3	-0.21	0.39	-10000	0	-0.81	148	148
MAPK1	-0.21	0.39	-10000	0	-0.81	148	148
NFKB1	0.027	0.029	-10000	0	-0.61	1	1
MAPK8	0.01	0.14	-10000	0	-0.7	14	14
DUSP1	0.02	0.026	-10000	0	-0.5	1	1
NF-kappa-B/RelA	-0.025	0.077	-10000	0	-0.26	1	1
actin cytoskeleton reorganization	-0.013	0.13	0.4	3	-0.66	9	12
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.081	0.18	0.26	1	-0.42	71	72
FER	-0.04	0.095	-10000	0	-0.37	10	10
RELA	0.029	0.003	-10000	0	-10000	0	0
ITK	-0.041	0.092	-10000	0	-0.24	12	12
SOS1	0.028	0.005	-10000	0	-10000	0	0
PLCG1	-0.063	0.2	0.38	14	-0.43	71	85
cytokine secretion	-0.025	0.049	-10000	0	-10000	0	0
SPHK1	-0.056	0.12	-10000	0	-0.41	26	26
PTK2	-0.014	0.14	0.4	3	-0.71	9	12
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.1	0.19	-10000	0	-0.53	55	55
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	-0.036	0.26	0.4	57	-0.5	51	108
MAP2K2	-0.22	0.39	-10000	0	-0.83	148	148
MAP2K1	-0.22	0.39	-10000	0	-0.83	148	148
MAP2K7	0.029	0.003	-10000	0	-10000	0	0
KLRG1/SHP2	-0.042	0.1	0.29	2	-0.36	7	9
MAP2K4	0.016	0.14	-10000	0	-0.82	12	12
Fc epsilon R1/FcgammaRIIB	-0.13	0.25	-10000	0	-0.56	88	88
mol:Choline	-0.082	0.17	0.34	17	-0.5	20	37
SHC/Grb2/SOS1	-0.012	0.11	-10000	0	-0.39	2	2
FYN	0.027	0.008	-10000	0	-10000	0	0
DOK1	0.028	0.005	-10000	0	-10000	0	0
PXN	-0.006	0.14	0.42	10	-0.67	8	18
HCLS1	-0.047	0.11	-10000	0	-0.41	18	18
PRKCB	-0.026	0.22	0.37	60	-0.36	66	126
FCGR2B	-0.066	0.2	-10000	0	-0.5	89	89
IGHE	-0.003	0.01	-10000	0	-10000	0	0
KLRG1/SHIP	-0.035	0.11	0.23	1	-0.4	9	10
LCP2	-0.009	0.12	-10000	0	-0.51	29	29
PLA2G4A	-0.042	0.098	-10000	0	-0.36	12	12
RASA1	0.024	0.03	-10000	0	-0.61	1	1
mol:Phosphatidic acid	-0.082	0.17	0.34	17	-0.5	20	37
IKK complex	0.009	0.16	0.32	63	-0.24	3	66
WIPF1	0.028	0.006	-10000	0	-10000	0	0

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.029	0.04	-10000	0	-0.38	4	4
ARNO/beta Arrestin1-2	0.022	0.061	-10000	0	-0.78	1	1
EGFR	0.019	0.06	-10000	0	-0.52	6	6
EPHA2	0.026	0.029	-10000	0	-0.61	1	1
USP6	0.027	0.024	-10000	0	-0.5	1	1
IQSEC1	0.02	0.013	-10000	0	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.39	0.16	-10000	0	-0.43	454	454
ARRB2	-0.002	0.061	-10000	0	-0.21	36	36
mol:GTP	0.003	0.043	0.18	7	-0.16	6	13
ARRB1	0.029	0.003	-10000	0	-10000	0	0
FBXO8	0.028	0.004	-10000	0	-10000	0	0
TSHR	-0.034	0.17	-10000	0	-0.5	58	58
EGF	-0.54	0.19	-10000	0	-0.61	460	460
somatostatin receptor activity	0	0	0.001	19	-0.001	26	45
ARAP2	0.026	0.04	-10000	0	-0.61	2	2
mol:GDP	-0.044	0.097	0.23	7	-0.3	31	38
mol:PI-3-4-5-P3	0	0	0.001	9	-0.001	11	20
ITGA2B	0.009	0.099	-10000	0	-0.51	18	18
ARF6	0.027	0.007	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.062	0.039	-10000	0	-0.35	2	2
ADAP1	0.021	0.057	-10000	0	-0.61	4	4
KIF13B	0.026	0.009	-10000	0	-10000	0	0
HGF/MET	0.019	0.091	-10000	0	-0.42	20	20
PXN	0.028	0.005	-10000	0	-10000	0	0
ARF6/GTP	-0.062	0.11	0.28	12	-0.31	30	42
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.32	0.14	-10000	0	-0.38	411	411
ADRB2	0.019	0.041	-10000	0	-0.61	2	2
receptor agonist activity	0	0	0	20	0	15	35
actin filament binding	0	0	0.001	20	-0.001	29	49
SRC	0.028	0.006	-10000	0	-10000	0	0
ITGB3	0.024	0.049	-10000	0	-0.61	3	3
GNAQ	0.028	0.006	-10000	0	-10000	0	0
EFA6/PI-4-5-P2	0	0.001	0.002	27	-0.001	14	41
ARF6/GDP	-0.041	0.11	0.27	5	-0.38	19	24
ARF6/GDP/GULP/ACAP1	-0.12	0.17	0.26	1	-0.4	71	72
alphaIIb/beta3 Integrin/paxillin/GIT1	0.056	0.073	-10000	0	-0.35	4	4
ACAP1	-0.18	0.26	-10000	0	-0.5	195	195
ACAP2	0.027	0.006	-10000	0	-10000	0	0
LHCGR/beta Arrestin2	0	0.083	-10000	0	-0.3	36	36
EFNA1	0.026	0.024	-10000	0	-0.5	1	1
HGF	0.003	0.11	-10000	0	-0.54	20	20
CYTH3	0.009	0.003	-10000	0	-10000	0	0
CYTH2	0.017	0.045	-10000	0	-0.99	1	1
NCK1	0.026	0.029	-10000	0	-0.61	1	1
fibronectin binding	0	0	0.001	31	-0.001	14	45
endosomal lumen acidification	0	0	0.001	3	-0.001	26	29
microtubule-based process	0	0	-10000	0	-0.001	1	1
GULP1	0.007	0.11	-10000	0	-0.59	17	17
GNAQ/ARNO	0.032	0.044	-10000	0	-0.93	1	1
mol:Phosphatidic acid	0	0	0	4	-10000	0	4
PIP3-E	0	0	0.001	2	0	8	10
MET	0.024	0.034	-10000	0	-0.5	2	2
GNA14	0.02	0.069	-10000	0	-0.61	6	6
GNA15	0.013	0.09	-10000	0	-0.5	15	15
GIT1	0.028	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	0.001	22	-0.001	20	42
GNA11	0.025	0.049	-10000	0	-0.61	3	3
LHCGR	-0.031	0.13	-10000	0	-0.5	35	35
AGTR1	-0.003	0.14	-10000	0	-0.6	25	25
desensitization of G-protein coupled receptor protein signaling pathway	0	0.082	-10000	0	-0.3	36	36
IPCEF1/ARNO	-0.24	0.11	-10000	0	-0.58	6	6
alphaIIb/beta3 Integrin	0.024	0.084	-10000	0	-0.38	21	21

Effects of Botulinum toxin

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
STX1A	0.007	0.037	0.19	2	-0.39	4	6
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.025	0.074	-10000	0	-0.39	15	15
STXBP1	0.027	0.029	-10000	0	-0.61	1	1
ACh/CHRNA1	-0.13	0.17	-10000	0	-0.32	217	217
RAB3GAP2/RIMS1/UNC13B	0.04	0.067	-10000	0	-0.33	15	15
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	0.009	0.097	-10000	0	-0.54	15	15
mol:ACh	0.004	0.043	0.1	43	-0.14	3	46
RAB3GAP2	0.028	0.006	-10000	0	-10000	0	0
STX1A/SNAP25/VAMP2	0.02	0.077	-10000	0	-0.35	8	8
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	-0.13	0.17	-10000	0	-0.32	217	217
UNC13B	0.028	0.006	-10000	0	-10000	0	0
CHRNA1	-0.2	0.26	-10000	0	-0.5	217	217
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	-0.048	0.16	-10000	0	-0.4	80	80
SNAP25	-0.018	0.063	-10000	0	-0.17	71	71
VAMP2	0.007	0.001	-10000	0	-10000	0	0
SYT1	-0.071	0.23	-10000	0	-0.6	80	80
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.022	0.038	-10000	0	-0.34	5	5
STX1A/SNAP25 fragment 1/VAMP2	0.02	0.077	-10000	0	-0.35	8	8

HIF-2-alpha transcription factor network

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
MMP14	-0.015	0.15	-10000	0	-0.71	19	19
oxygen homeostasis	-0.003	0.013	-10000	0	-10000	0	0
TCEB2	0.024	0.044	-10000	0	-0.54	3	3
TCEB1	0.027	0.007	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.12	0.12	-10000	0	-0.41	9	9
EPO	-0.25	0.27	-10000	0	-0.68	75	75
FIH (dimer)	0.02	0.022	-10000	0	-10000	0	0
APEX1	0.02	0.022	-10000	0	-10000	0	0
SERPINE1	-0.21	0.27	-10000	0	-0.71	63	63
FLT1	0.003	0.12	-10000	0	-0.73	9	9
ADORA2A	-0.2	0.24	0.48	3	-0.67	42	45
germ cell development	-0.26	0.3	-10000	0	-0.66	126	126
SLC11A2	-0.19	0.24	-10000	0	-0.67	38	38
BHLHE40	-0.2	0.23	-10000	0	-0.67	39	39
HIF1AN	0.02	0.022	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.18	0.18	-10000	0	-0.47	32	32
ETS1	0.042	0.011	-10000	0	-10000	0	0
CITED2	-0.034	0.17	-10000	0	-0.72	21	21
KDR	0.012	0.097	-10000	0	-0.78	6	6
PGK1	-0.19	0.24	-10000	0	-0.67	40	40
SIRT1	0.027	0.006	-10000	0	-10000	0	0
response to hypoxia	-0.002	0.004	-10000	0	-10000	0	0
HIF2A/ARNT	-0.21	0.29	-10000	0	-0.78	43	43
EPAS1	-0.16	0.12	-10000	0	-0.37	42	42
SP1	0.034	0.012	-10000	0	-10000	0	0
ABCG2	-0.19	0.24	-10000	0	-0.68	40	40
EFNA1	-0.19	0.24	-10000	0	-0.67	41	41
FXN	-0.2	0.24	0.48	2	-0.66	42	44
POU5F1	-0.27	0.31	-10000	0	-0.68	128	128
neuron apoptosis	0.21	0.28	0.76	43	-10000	0	43
EP300	0.027	0.029	-10000	0	-0.61	1	1
EGLN3	-0.45	0.18	-10000	0	-0.52	451	451
EGLN2	0.022	0.02	-10000	0	-10000	0	0
EGLN1	0.02	0.022	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.036	0.041	-10000	0	-0.33	3	3
VHL	0.02	0.019	-10000	0	-0.3	1	1
ARNT	0.019	0.023	-10000	0	-10000	0	0
SLC2A1	-0.21	0.26	0.45	2	-0.73	48	50
TWIST1	-0.2	0.24	0.48	2	-0.64	45	47
ELK1	0.035	0.007	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.14	0.16	-10000	0	-0.5	11	11
VEGFA	-0.28	0.31	-10000	0	-0.68	138	138
CREBBP	0.028	0.006	-10000	0	-10000	0	0

Calcium signaling in the CD4+ TCR pathway

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
NFATC1	-0.024	0.044	-10000	0	-10000	0	0
NFATC2	-0.024	0.052	-10000	0	-0.42	3	3
NFATC3	-0.024	0.043	-10000	0	-10000	0	0
CD40LG	-0.25	0.3	0.4	2	-0.71	101	103
PTGS2	-0.24	0.29	0.4	1	-0.66	100	101
JUNB	0.026	0.04	-10000	0	-0.61	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.013	0.031	-10000	0	-10000	0	0
CaM/Ca2+	-0.013	0.031	-10000	0	-10000	0	0
CALM1	0.003	0.027	-10000	0	-10000	0	0
JUN	0.002	0.028	-10000	0	-10000	0	0
mol:Ca2+	-0.016	0.015	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.006	0.015	-10000	0	-10000	0	0
FOSL1	0.004	0.11	-10000	0	-0.5	24	24
CREM	0.028	0.004	-10000	0	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.13	0.18	-10000	0	-0.53	27	27
FOS	-0.013	0.096	-10000	0	-0.61	12	12
IFNG	-0.32	0.36	0.4	1	-0.69	217	218
AP-1/NFAT1-c-4	-0.27	0.33	-10000	0	-0.77	98	98
FASLG	-0.33	0.35	0.4	1	-0.69	220	221
NFAT1-c-4/ICER1	-0.062	0.1	-10000	0	-0.44	3	3
IL2RA	-0.27	0.32	0.4	1	-0.74	107	108
FKBP12/FK506	0.021	0.004	-10000	0	-10000	0	0
CSF2	-0.22	0.27	0.4	1	-0.67	87	88
JunB/Fra1/NFAT1-c-4	-0.065	0.12	-10000	0	-0.42	9	9
IL4	-0.22	0.26	0.4	1	-0.65	82	83
IL2	-0.006	0.12	-10000	0	-0.86	7	7
IL3	-0.013	0.076	-10000	0	-0.69	1	1
FKBP1A	0.028	0.005	-10000	0	-10000	0	0
BATF3	-0.018	0.15	-10000	0	-0.5	44	44
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.028	0.006	-10000	0	-10000	0	0

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.037	0.014	-10000	0	-10000	0	0
VLDLR	0.028	0.006	-10000	0	-10000	0	0
CRKL	0.028	0.004	-10000	0	-10000	0	0
LRPAP1	0.028	0.004	-10000	0	-10000	0	0
FYN	0.027	0.008	-10000	0	-10000	0	0
ITGA3	0.027	0.024	-10000	0	-0.5	1	1
RELN/VLDLR/Fyn	-0.083	0.2	-10000	0	-0.38	153	153
MAPK8IP1/MKK7/MAP3K11/JNK1	0.077	0.045	-10000	0	-0.49	2	2
AKT1	-0.063	0.13	-10000	0	-0.37	13	13
MAP2K7	0.029	0.003	-10000	0	-10000	0	0
RAPGEF1	0.028	0.005	-10000	0	-10000	0	0
DAB1	0.012	0.08	-10000	0	-0.5	12	12
RELN/LRP8/DAB1	-0.082	0.18	-10000	0	-0.35	162	162
LRPAP1/LRP8	0.04	0.02	-10000	0	-0.36	1	1
RELN/LRP8/DAB1/Fyn	-0.069	0.18	-10000	0	-0.34	147	147
DAB1/alpha3/beta1 Integrin	-0.06	0.17	-10000	0	-0.54	1	1
long-term memory	-0.098	0.2	-10000	0	-0.56	18	18
DAB1/LIS1	-0.055	0.18	-10000	0	-0.56	1	1
DAB1/CRLK/C3G	-0.061	0.17	-10000	0	-0.54	1	1
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
DAB1/NCK2	-0.055	0.18	-10000	0	-0.56	1	1
ARHGEF2	0.027	0.006	-10000	0	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	-0.047	0.19	-10000	0	-0.53	68	68
CDK5R1	0.028	0.004	-10000	0	-10000	0	0
RELN	-0.16	0.29	-10000	0	-0.61	153	153
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
RELN/LRP8/Fyn	-0.083	0.2	-10000	0	-0.38	153	153
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.1	0.2	-10000	0	-0.57	20	20
MAPK8	0.027	0.029	-10000	0	-0.61	1	1
RELN/VLDLR/DAB1	-0.083	0.18	-10000	0	-0.35	161	161
ITGB1	0.028	0.004	-10000	0	-10000	0	0
MAP1B	-0.083	0.17	-10000	0	-0.34	130	130
RELN/LRP8	-0.082	0.2	-10000	0	-0.38	153	153
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.061	0.19	-10000	0	-0.34	130	130
PI3K	0.036	0.034	-10000	0	-0.45	2	2
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.041	0.02	-10000	0	-0.36	1	1
RAP1A	-0.055	0.17	0.4	7	-0.51	1	8
PAFAH1B1	0.028	0.005	-10000	0	-10000	0	0
MAPK8IP1	0.026	0.04	-10000	0	-0.61	2	2
CRLK/C3G	0.041	0.009	-10000	0	-10000	0	0
GRIN2B	0.023	0.034	-10000	0	-0.5	2	2
NCK2	0.028	0.005	-10000	0	-10000	0	0
neuron differentiation	-0.035	0.13	-10000	0	-0.38	29	29
neuron adhesion	-0.048	0.17	0.38	10	-0.49	1	11
LRP8	0.027	0.024	-10000	0	-0.5	1	1
GSK3B	-0.058	0.12	-10000	0	-0.35	9	9
RELN/VLDLR/DAB1/Fyn	-0.07	0.18	-10000	0	-0.33	148	148
MAP3K11	0.027	0.028	-10000	0	-0.61	1	1
RELN/VLDLR/DAB1/P13K	-0.067	0.14	-10000	0	-0.28	138	138
CDK5	0.026	0.009	-10000	0	-10000	0	0
MAPT	0.01	0.096	0.72	5	-0.57	6	11
neuron migration	-0.067	0.18	0.45	4	-0.49	2	6
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.035	0.13	-10000	0	-0.38	29	29
RELN/VLDLR	-0.064	0.19	-10000	0	-0.35	148	148

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.16	0.17	-10000	0	-0.55	27	27
IHH	-0.075	0.18	-10000	0	-0.65	44	44
SHH Np/Cholesterol/GAS1	0.003	0.093	-10000	0	-0.35	29	29
LRPAP1	0.028	0.004	-10000	0	-10000	0	0
dorsoventral neural tube patterning	-0.003	0.092	0.35	29	-10000	0	29
SMO/beta Arrestin2	-0.076	0.14	-10000	0	-0.49	26	26
SMO	-0.086	0.14	-10000	0	-0.51	25	25
AKT1	-0.034	0.11	-10000	0	-0.49	15	15
ARRB2	0.027	0.029	-10000	0	-0.62	1	1
BOC	0.027	0.008	-10000	0	-10000	0	0
ADRBK1	0.029	0.003	-10000	0	-10000	0	0
heart looping	-0.085	0.14	-10000	0	-0.5	25	25
STIL	-0.062	0.12	-10000	0	-0.4	27	27
DHH N/PTCH2	0.01	0.11	-10000	0	-0.39	35	35
DHH N/PTCH1	-0.094	0.14	-10000	0	-0.47	31	31
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
DHH	0.014	0.093	-10000	0	-0.61	11	11
PTHLH	-0.24	0.24	-10000	0	-0.74	35	35
determination of left/right symmetry	-0.085	0.14	-10000	0	-0.5	25	25
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
skeletal system development	-0.24	0.23	-10000	0	-0.73	35	35
IHH N/Hhip	-0.15	0.24	-10000	0	-0.5	153	153
DHH N/Hhip	-0.087	0.22	-10000	0	-0.45	129	129
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.085	0.14	-10000	0	-0.5	25	25
pancreas development	-0.12	0.27	-10000	0	-0.59	126	126
HHAT	0.028	0.006	-10000	0	-10000	0	0
PI3K	0.036	0.034	-10000	0	-0.45	2	2
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.008	0.14	-10000	0	-0.56	31	31
somite specification	-0.085	0.14	-10000	0	-0.5	25	25
SHH Np/Cholesterol/PTCH1	-0.074	0.12	-10000	0	-0.42	27	27
SHH Np/Cholesterol/PTCH2	0.008	0.08	-10000	0	-0.3	31	31
SHH Np/Cholesterol/Megalin	-0.004	0.11	-10000	0	-0.39	35	35
SHH	0.009	0.066	-10000	0	-0.45	10	10
catabolic process	-0.11	0.14	-10000	0	-0.48	32	32
SMO/Vitamin D3	-0.076	0.13	-10000	0	-0.46	27	27
SHH Np/Cholesterol/Hhip	-0.064	0.17	-10000	0	-0.36	112	112
LRP2	-0.021	0.17	-10000	0	-0.56	42	42
receptor-mediated endocytosis	-0.089	0.15	-10000	0	-0.62	17	17
SHH Np/Cholesterol/BOC	0.02	0.054	-10000	0	-0.35	10	10
SHH Np/Cholesterol/CDO	-0.011	0.1	-10000	0	-0.29	60	60
mesenchymal cell differentiation	0.064	0.16	0.36	112	-10000	0	112
mol:Vitamin D3	-0.069	0.13	-10000	0	-0.42	27	27
IHH N/PTCH2	-0.053	0.15	-10000	0	-0.42	67	67
CDON	-0.032	0.17	-10000	0	-0.5	58	58
IHH N/PTCH1	-0.11	0.14	-10000	0	-0.49	32	32
Megalin/LRPAP1	0.004	0.12	-10000	0	-0.45	34	34
PTCH2	0.002	0.12	-10000	0	-0.5	25	25
SHH Np/Cholesterol	0.01	0.052	-10000	0	-0.35	10	10
PTCH1	-0.11	0.14	-10000	0	-0.48	32	32
HHIP	-0.13	0.27	-10000	0	-0.59	126	126

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	0.008	0.018	-10000	0	-0.39	1	1
ADCY5	-0.007	0.076	-10000	0	-0.39	19	19
ADCY6	0.008	0.033	-10000	0	-0.73	1	1
ADCY7	-0.001	0.056	-10000	0	-0.31	16	16
ADCY1	0	0.057	0.18	1	-0.38	11	12
ADCY2	-0.054	0.14	0.18	20	-0.31	109	129
ADCY3	0.009	0.018	-10000	0	-0.39	1	1
ADCY8	-0.085	0.15	0.18	7	-0.31	151	158
PRKCE	0.009	0.021	-10000	0	-0.45	1	1
ADCY9	0.008	0.018	-10000	0	-0.39	1	1
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	-0.032	0.12	0.28	21	-0.28	36	57

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.027	0.008	-10000	0	-10000	0	0
VLDLR	0.028	0.006	-10000	0	-10000	0	0
LRPAP1	0.028	0.004	-10000	0	-10000	0	0
NUDC	0.028	0.006	-10000	0	-10000	0	0
RELN/LRP8	-0.082	0.2	-10000	0	-0.38	153	153
CaM/Ca2+	0.02	0.006	-10000	0	-10000	0	0
KATNA1	0.026	0.008	-10000	0	-10000	0	0
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	-0.077	0.18	-10000	0	-0.35	148	148
IQGAP1/CaM	0.039	0.012	-10000	0	-10000	0	0
DAB1	0.012	0.08	-10000	0	-0.5	12	12
IQGAP1	0.029	0.003	-10000	0	-10000	0	0
PLA2G7	-0.38	0.23	-10000	0	-0.51	389	389
CALM1	0.027	0.008	-10000	0	-10000	0	0
DYNLT1	0.026	0.008	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	0.04	0.02	-10000	0	-0.36	1	1
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0.028	0.005	-10000	0	-10000	0	0
CDK5R1	0.028	0.004	-10000	0	-10000	0	0
LIS1/Poliovirus Protein 3A	0.015	0.004	-10000	0	-10000	0	0
CDK5R2	-0.041	0.18	-10000	0	-0.51	62	62
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.092	0.2	-10000	0	-0.38	161	161
YWHAE	0.028	0.005	-10000	0	-10000	0	0
NDEL1/14-3-3 E	-0.05	0.18	0.32	30	-0.44	11	41
MAP1B	0.007	0.007	-10000	0	-10000	0	0
RAC1	0.019	0.008	-10000	0	-10000	0	0
p35/CDK5	-0.07	0.15	-10000	0	-10000	0	0
RELN	-0.16	0.29	-10000	0	-0.61	153	153
PAFAH/LIS1	-0.22	0.15	-10000	0	-0.31	376	376
LIS1/CLIP170	0.034	0.01	-10000	0	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.052	0.12	-10000	0	-0.39	4	4
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.06	0.14	-10000	0	-0.42	12	12
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	-0.081	0.15	-10000	0	-0.46	12	12
LIS1/IQGAP1	0.034	0.01	-10000	0	-10000	0	0
RHOA	0.014	0.01	-10000	0	-10000	0	0
PAFAH1B1	0.02	0.005	-10000	0	-10000	0	0
PAFAH1B3	0.027	0.028	-10000	0	-0.61	1	1
PAFAH1B2	0.027	0.028	-10000	0	-0.61	1	1
MAP1B/LIS1/Dynein heavy chain	0.036	0.023	-10000	0	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.047	0.17	0.32	22	-0.43	10	32
LRP8	0.027	0.024	-10000	0	-0.5	1	1
NDEL1/Katanin 60	-0.052	0.17	0.32	27	-0.44	11	38
P39/CDK5	-0.096	0.17	-10000	0	-0.54	14	14
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.034	0.01	-10000	0	-10000	0	0
CDK5	-0.085	0.16	-10000	0	-10000	0	0
PPP2R5D	0.028	0.006	-10000	0	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.029	0.009	-10000	0	-10000	0	0
CSNK2A1	0.028	0.005	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.068	0.18	-10000	0	-0.34	56	56
RELN/VLDLR	-0.064	0.19	-10000	0	-0.35	148	148
CDC42	0.02	0.006	-10000	0	-10000	0	0

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.025	0.047	-10000	0	-0.5	4	4
CD4-positive alpha-beta T cell lineage commitment	0	0.001	-10000	0	-10000	0	0
cytokine production during immune response	0.048	0.13	0.38	26	-0.31	1	27
IL27/IL27R/JAK1	-0.01	0.25	0.66	3	-0.6	28	31
TBX21	-0.11	0.31	0.57	9	-0.56	107	116
IL12B	-0.038	0.16	-10000	0	-0.51	52	52
IL12A	0.006	0.011	0.19	1	-10000	0	1
IL6ST	-0.003	0.11	-10000	0	-0.6	16	16
IL27RA/JAK1	0.014	0.06	-10000	0	-10000	0	0
IL27	-0.018	0.13	-10000	0	-0.52	32	32
TYK2	0.01	0.025	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.009	0.1	-10000	0	-0.46	1	1
T-helper 2 cell differentiation	0.048	0.13	0.38	26	-0.31	1	27
T cell proliferation during immune response	0.048	0.13	0.38	26	-0.31	1	27
MAPKKK cascade	-0.048	0.13	0.31	1	-0.38	26	27
STAT3	0.028	0.004	-10000	0	-10000	0	0
STAT2	0.028	0.005	-10000	0	-10000	0	0
STAT1	0.028	0.025	-10000	0	-0.51	1	1
IL12RB1	-0.14	0.25	-10000	0	-0.51	158	158
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.081	0.27	0.56	9	-0.54	64	73
IL27/IL27R/JAK2/TYK2	-0.049	0.13	0.31	1	-0.39	26	27
positive regulation of T cell mediated cytotoxicity	-0.048	0.13	0.31	1	-0.38	26	27
STAT1 (dimer)	0.047	0.39	0.51	137	-0.64	56	193
JAK2	0.014	0.021	-10000	0	-10000	0	0
JAK1	0.03	0.009	-10000	0	-10000	0	0
STAT2 (dimer)	-0.031	0.14	0.39	2	-0.44	7	9
T cell proliferation	-0.075	0.15	-10000	0	-0.46	28	28
IL12/IL12R/TYK2/JAK2	-0.079	0.14	-10000	0	-0.75	3	3
IL17A	-0.009	0.099	-10000	0	-0.46	1	1
mast cell activation	0.048	0.13	0.38	26	-0.31	1	27
IFNG	-0.023	0.051	0.12	5	-0.089	52	57
T cell differentiation	-0.007	0.01	0.017	4	-0.021	119	123
STAT3 (dimer)	-0.032	0.14	0.39	2	-0.43	8	10
STAT5A (dimer)	-0.032	0.14	0.39	2	-0.43	8	10
STAT4 (dimer)	-0.047	0.16	0.39	2	-0.48	26	28
STAT4	-0.003	0.12	-10000	0	-0.5	29	29
T cell activation	-0.008	0.005	0.06	1	-10000	0	1
IL27R/JAK2/TYK2	-0.01	0.1	-10000	0	-0.44	4	4
GATA3	-0.59	0.64	0.5	1	-1.3	245	246
IL18	0.006	0.038	0.19	1	-0.36	5	6
positive regulation of mast cell cytokine production	-0.031	0.14	0.39	2	-0.43	8	10
IL27/EBI3	-0.054	0.19	-10000	0	-0.46	85	85
IL27RA	-0.003	0.044	-10000	0	-10000	0	0
IL6	-0.041	0.18	-10000	0	-0.55	60	60
STAT5A	0.028	0.004	-10000	0	-10000	0	0
monocyte differentiation	-0.002	0.002	-10000	0	-10000	0	0
IL2	-0.01	0.048	-10000	0	-10000	0	0
IL1B	0.005	0.042	-10000	0	-0.38	6	6
EBI3	-0.058	0.19	-10000	0	-0.52	75	75
TNF	0.003	0.052	-10000	0	-0.41	8	8

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.008	0.12	-9999	-0.39	43	43
EFNA5	-0.022	0.16	-9999	-0.6	37	37
FYN	0.009	0.13	-9999	-0.36	43	43
neuron projection morphogenesis	-0.008	0.12	-9999	-0.39	43	43
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.008	0.12	-9999	-0.39	43	43
EPHA5	0.013	0.068	-9999	-0.52	8	8

IL2 signaling events mediated by STAT5

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
GAB2	0.029	0.003	-10000	0	-10000	0	0
ELF1	-0.02	0.11	-10000	0	-0.47	4	4
CCNA2	-0.076	0.21	-10000	0	-0.51	100	100
PIK3CA	0.027	0.029	-10000	0	-0.61	1	1
JAK3	-0.078	0.21	-10000	0	-0.5	103	103
PIK3R1	0.026	0.029	-10000	0	-0.61	1	1
JAK1	0.028	0.006	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.039	0.14	-10000	0	-0.46	19	19
SHC1	0.028	0.007	-10000	0	-10000	0	0
SP1	0.034	0.017	-10000	0	-10000	0	0
IL2RA	-0.063	0.18	-10000	0	-0.43	101	101
IL2RB	-0.25	0.27	-10000	0	-0.5	270	270
SOS1	0.029	0.005	-10000	0	-10000	0	0
IL2RG	-0.006	0.13	-10000	0	-0.51	34	34
G1/S transition of mitotic cell cycle	0.006	0.11	0.43	7	-0.46	4	11
PTPN11	0.029	0.005	-10000	0	-10000	0	0
CCND2	0.025	0.029	-10000	0	-0.43	2	2
LCK	0.005	0.11	-10000	0	-0.51	22	22
GRB2	0.029	0.005	-10000	0	-10000	0	0
IL2	0.014	0.073	-10000	0	-0.5	10	10
CDK6	0.024	0.03	-10000	0	-0.61	1	1
CCND3	-0.026	0.13	0.49	1	-0.49	1	2

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.027	0.01	-9999	-10000	0	0
SVIL	0.027	0.009	-9999	-10000	0	0
ZNF318	0.028	0.011	-9999	-10000	0	0
JMJD2C	0	0.015	-9999	-0.076	17	17
T-DHT/AR/Ubc9	-0.081	0.087	-9999	-0.45	21	21
CARM1	0.029	0.003	-9999	-10000	0	0
PRDX1	0.028	0.006	-9999	-10000	0	0
PELP1	0.028	0.005	-9999	-10000	0	0
CTNNB1	0.019	0.015	-9999	-10000	0	0
AKT1	0.027	0.009	-9999	-10000	0	0
PTK2B	0.025	0.01	-9999	-10000	0	0
MED1	0.028	0.005	-9999	-10000	0	0
MAK	0.027	0.026	-9999	-0.5	1	1
response to oxidative stress	0	0.001	-9999	-10000	0	0
HIP1	0.02	0.058	-9999	-0.62	4	4
GSN	0.026	0.012	-9999	-10000	0	0
NCOA2	0.017	0.08	-9999	-0.61	8	8
NCOA6	0.026	0.011	-9999	-10000	0	0
DNA-PK	0.052	0.021	-9999	-10000	0	0
NCOA4	0.028	0.005	-9999	-10000	0	0
PIAS3	0.027	0.009	-9999	-10000	0	0
cell proliferation	-0.044	0.099	-9999	-0.53	18	18
XRCC5	0.028	0.007	-9999	-10000	0	0
UBE3A	0.027	0.014	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.096	0.11	-9999	-0.47	36	36
FHL2	-0.052	0.11	-9999	-0.71	9	9
RANBP9	0.027	0.01	-9999	-10000	0	0
JMJD1A	-0.12	0.052	-9999	-0.14	442	442
CDK6	0.024	0.03	-9999	-0.61	1	1
TGFB1I1	0.025	0.026	-9999	-0.5	1	1
T-DHT/AR/CyclinD1	-0.094	0.1	-9999	-0.41	40	40
XRCC6	0.029	0.005	-9999	-10000	0	0
T-DHT/AR	-0.15	0.1	-9999	-0.42	31	31
CTDSP1	0.027	0.007	-9999	-10000	0	0
CTDSP2	0.029	0.01	-9999	-10000	0	0
BRCA1	0.027	0.009	-9999	-10000	0	0
TCF4	0.029	0.008	-9999	-10000	0	0
CDKN2A	-0.49	0.11	-9999	-0.51	489	489
SRF	0.034	0.015	-9999	-10000	0	0
NKX3-1	-0.21	0.12	-9999	-0.51	45	45
KLK3	0.017	0.075	-9999	-10000	0	0
TMF1	0.023	0.012	-9999	-10000	0	0
HNRNPA1	0.029	0.007	-9999	-10000	0	0
AOF2	-0.001	0.005	-9999	-10000	0	0
APPL1	0.015	0.012	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.082	0.087	-9999	-0.44	22	22
AR	-0.08	0.13	-9999	-0.65	23	23
UBA3	0.022	0.012	-9999	-10000	0	0
PATZ1	0.029	0.006	-9999	-10000	0	0
PAWR	0.027	0.029	-9999	-0.61	1	1
PRKDC	0.027	0.008	-9999	-10000	0	0
PA2G4	0.029	0.007	-9999	-10000	0	0
UBE2I	0.028	0.006	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.074	0.08	-9999	-0.4	23	23
RPS6KA3	0.026	0.031	-9999	-0.63	1	1
T-DHT/AR/ARA70	-0.083	0.086	-9999	-0.44	22	22
LATS2	0.029	0.006	-9999	-10000	0	0
T-DHT/AR/PRX1	-0.074	0.08	-9999	-0.4	23	23
Cyclin D3/CDK11 p58	0.021	0.004	-9999	-10000	0	0
VAV3	0.01	0.1	-9999	-0.61	14	14
KLK2	-0.074	0.081	-9999	-0.45	18	18
CASP8	0.028	0.006	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.075	0.097	-9999	-0.44	24	24
TMPRSS2	-0.84	0.32	-9999	-0.95	446	446
CCND1	0.01	0.098	-9999	-0.5	18	18
PIAS1	0.027	0.014	-9999	-10000	0	0
mol:T-DHT	-0.057	0.024	-9999	-0.067	432	432
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.026	0.017	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.076	0.09	-9999	-0.45	20	20
CMTM2	0.016	0.077	-9999	-0.5	11	11
SNURF	0.008	0.11	-9999	-0.61	16	16
ZMIZ1	-0.049	0.033	-9999	-10000	0	0
CCND3	0.028	0.006	-9999	-10000	0	0
TGIF1	0.029	0.006	-9999	-10000	0	0
FKBP4	0.026	0.011	-9999	-10000	0	0

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.04	0.023	-10000	0	-0.45	1	1
Necdin/E2F1	-0.002	0.12	-10000	0	-0.36	54	54
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.027	0.13	-10000	0	-0.49	8	8
NGF (dimer)/p75(NTR)/BEX1	-0.16	0.24	-10000	0	-0.4	241	241
NT-4/5 (dimer)/p75(NTR)	0.006	0.11	-10000	0	-0.38	38	38
IKBKB	0.027	0.008	-10000	0	-10000	0	0
AKT1	-0.005	0.13	0.41	4	-0.46	11	15
IKBKG	0.028	0.004	-10000	0	-10000	0	0
BDNF	-0.042	0.18	-10000	0	-0.51	67	67
MGDIs/NGR/p75(NTR)/LINGO1	0.014	0.12	-10000	0	-0.33	56	56
FURIN	0.029	0.003	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.015	0.15	-10000	0	-0.33	94	94
LINGO1	0.008	0.1	-10000	0	-0.5	20	20
Sortilin/TRAF6/NRIF	0.035	0.02	-10000	0	-10000	0	0
proBDNF (dimer)	-0.042	0.18	-10000	0	-0.51	67	67
NTRK1	-0.016	0.16	-10000	0	-0.58	36	36
RTN4R	0.022	0.06	-10000	0	-0.52	6	6
neuron apoptosis	-0.019	0.13	0.45	6	-0.55	7	13
IRAK1	0.029	0.003	-10000	0	-10000	0	0
SHC1	-0.027	0.13	-10000	0	-0.33	73	73
ARHGDIA	0.027	0.029	-10000	0	-0.61	1	1
RhoA/GTP	0.015	0.01	-10000	0	-10000	0	0
Gamma Secretase	0.076	0.029	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.016	0.14	-10000	0	-0.46	11	11
MAGEH1	0.029	0.003	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	0.014	0.14	-10000	0	-0.44	13	13
Mammalian IAPs/DIABLO	0.018	0.12	-10000	0	-0.28	75	75
proNGF (dimer)	-0.021	0.15	-10000	0	-0.5	47	47
MAGED1	0.029	0.003	-10000	0	-10000	0	0
APP	0.028	0.006	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.017	0.049	-10000	0	-0.53	4	4
ZNF274	0.029	0.003	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.014	0.12	-10000	0	-0.43	11	11
NGF	-0.021	0.15	-10000	0	-0.5	47	47
cell cycle arrest	0.016	0.15	0.36	10	-0.54	7	17
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.003	0.084	-10000	0	-0.34	16	16
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.024	0.098	-10000	0	-0.32	38	38
NCSTN	0.027	0.006	-10000	0	-10000	0	0
mol:GTP	0	0.14	-10000	0	-0.33	73	73
PSENEN	0.029	0.003	-10000	0	-10000	0	0
mol:ceramide	-0.022	0.12	-10000	0	-0.45	11	11
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.009	0.059	-10000	0	-0.43	3	3
p75(NTR)/beta APP	0.014	0.1	-10000	0	-0.37	33	33
BEX1	-0.21	0.31	-10000	0	-0.61	189	189
mol:GDP	-0.039	0.12	-10000	0	-0.34	73	73
NGF (dimer)	-0.23	0.24	-10000	0	-0.42	294	294
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.03	0.12	-10000	0	-0.31	55	55
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
RAC1/GTP	-0.001	0.12	-10000	0	-0.29	67	67
MYD88	0.02	0.013	-10000	0	-10000	0	0
CHUK	0.028	0.006	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	0	0.14	-10000	0	-0.33	73	73
RHOB	0.028	0.005	-10000	0	-10000	0	0
RHOA	0.021	0.013	-10000	0	-10000	0	0
MAGE-G1/E2F1	0	0.12	-10000	0	-0.36	52	52
NT3 (dimer)	0.022	0.059	-10000	0	-0.57	5	5
TP53	-0.024	0.12	0.34	3	-0.49	6	9
PRDM4	-0.021	0.12	-10000	0	-0.47	10	10
BDNF (dimer)	-0.27	0.27	-10000	0	-0.46	297	297
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
SORT1	0.027	0.029	-10000	0	-0.61	1	1
activation of caspase activity	0.022	0.13	-10000	0	-0.48	8	8
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.016	0.14	-10000	0	-0.46	11	11
RHOC	0.028	0.005	-10000	0	-10000	0	0
XIAP	0.029	0.003	-10000	0	-10000	0	0
MAPK10	-0.009	0.13	0.45	7	-0.44	6	13
DIABLO	0.028	0.005	-10000	0	-10000	0	0
SMPD2	-0.022	0.12	-10000	0	-0.46	11	11
APH1B	0.029	0.003	-10000	0	-10000	0	0
APH1A	0.027	0.006	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.001	0.14	-10000	0	-0.34	74	74
PSEN1	0.027	0.008	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.04	0.012	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	0.009	0.11	-10000	0	-0.38	38	38
MAPK8	-0.009	0.12	0.43	7	-0.41	5	12
MAPK9	-0.013	0.11	0.45	6	-0.41	5	11
APAF1	0.028	0.005	-10000	0	-10000	0	0
NTF3	0.022	0.059	-10000	0	-0.57	5	5
NTF4	0.017	0.049	-10000	0	-0.53	4	4
NDN	0.026	0.04	-10000	0	-0.61	2	2
RAC1/GDP	0.019	0.007	-10000	0	-10000	0	0
RhoA-B-C/GDP	0.007	0.12	-10000	0	-0.47	7	7
p75 CTF/Sortilin/TRAF6/NRIF	0.068	0.027	-10000	0	-0.35	1	1
RhoA-B-C/GTP	-0.001	0.14	-10000	0	-0.33	73	73
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.014	0.14	-10000	0	-0.44	10	10
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.003	0.15	-10000	0	-0.47	10	10
PRKACB	0.028	0.005	-10000	0	-10000	0	0
proBDNF (dimer)/p75 ECD	-0.012	0.14	-10000	0	-0.36	66	66
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.054	0.19	-10000	0	-0.5	79	79
BIRC2	0.028	0.004	-10000	0	-10000	0	0
neuron projection morphogenesis	0.035	0.14	0.32	5	-0.42	7	12
BAD	0.007	0.13	0.47	10	-0.43	5	15
RIPK2	0.026	0.024	-10000	0	-0.5	1	1
NGFR	-0.008	0.14	-10000	0	-0.51	34	34
CYCS	-0.017	0.12	0.44	2	-0.49	9	11
ADAM17	0.028	0.005	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.013	0.14	-10000	0	-0.48	10	10
BCL2L11	0.008	0.13	0.46	10	-0.44	5	15
BDNF (dimer)/p75(NTR)	-0.037	0.17	-10000	0	-0.38	94	94
PI3K	0.01	0.13	-10000	0	-0.31	68	68
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.016	0.14	-10000	0	-0.46	11	11
NDNL2	0.029	0.003	-10000	0	-10000	0	0
YWHAE	0.028	0.005	-10000	0	-10000	0	0
PRKCI	0.027	0.007	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.022	0.16	-10000	0	-0.39	73	73
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.016	0.14	-10000	0	-0.46	11	11
TRAF6	0.029	0.003	-10000	0	-10000	0	0
RAC1	0.026	0.009	-10000	0	-10000	0	0
PRKCZ	0.024	0.049	-10000	0	-0.61	3	3
PLG	-0.29	0.31	-10000	0	-0.58	265	265
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.038	0.13	-10000	0	-0.43	22	22
SQSTM1	0.021	0.013	-10000	0	-10000	0	0
NGFRAP1	0.029	0.003	-10000	0	-10000	0	0
CASP3	0.011	0.13	0.46	10	-0.4	5	15
E2F1	-0.027	0.16	-10000	0	-0.5	52	52
CASP9	0.028	0.006	-10000	0	-10000	0	0
IKK complex	0.023	0.12	-10000	0	-0.46	1	1
NGF (dimer)/TRKA	-0.03	0.16	-10000	0	-0.4	79	79
MMP7	-0.082	0.24	-10000	0	-0.6	89	89
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.028	0.13	-10000	0	-0.49	8	8
MMP3	-0.024	0.15	-10000	0	-0.5	46	46
APAF-1/Caspase 9	-0.044	0.11	-10000	0	-0.4	9	9

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0.038	0.067	0.14	148	-0.14	2	150
BUB1B	-0.003	0.073	0.2	8	-0.25	27	35
PLK1	-0.002	0.042	0.15	11	-0.14	7	18
PLK1S1	0.008	0.03	0.15	9	-0.19	1	10
KIF2A	0.016	0.083	0.24	46	-0.31	3	49
regulation of mitotic centrosome separation	-0.002	0.042	0.15	11	-0.14	7	18
GOLGA2	0.028	0.006	-10000	0	-10000	0	0
Hec1/SPC24	-0.056	0.19	0.18	1	-0.37	119	120
WEE1	0.013	0.053	0.23	4	-0.76	1	5
cytokinesis	-0.034	0.15	0.24	17	-0.25	91	108
PP2A-alpha B56	-0.011	0.1	-10000	0	-0.74	3	3
AURKA	0.006	0.03	0.14	6	-0.14	3	9
PICH/PLK1	-0.011	0.092	-10000	0	-0.44	17	17
CENPE	-0.032	0.11	0.27	3	-0.32	60	63
RhoA/GTP	0.015	0.01	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.016	0.083	0.24	46	-0.31	3	49
PPP2CA	0.022	0.012	-10000	0	-10000	0	0
FZR1	0.027	0.028	-10000	0	-0.61	1	1
TPX2	-0.011	0.062	0.15	15	-0.12	82	97
PAK1	0.029	0.003	-10000	0	-10000	0	0
SPC24	-0.026	0.16	-10000	0	-0.51	52	52
FBXW11	0.022	0.013	-10000	0	-10000	0	0
CLSPN	-0.013	0.068	0.14	3	-0.18	58	61
GORASP1	0.02	0.013	-10000	0	-10000	0	0
metaphase	-0.001	0.005	0.017	20	-0.013	9	29
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	-0.002	0.024	0.08	13	-0.069	9	22
G2 phase of mitotic cell cycle	0	0.003	0.019	3	-10000	0	3
STAG2	0.029	0.003	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	-0.11	0.22	-10000	0	-0.46	143	143
spindle elongation	-0.002	0.042	0.15	11	-0.14	7	18
ODF2	0.028	0.006	-10000	0	-10000	0	0
BUB1	-0.035	0.1	-10000	0	-0.64	7	7
TPT1	0.003	0.038	0.15	4	-0.2	11	15
CDC25C	-0.016	0.091	0.17	12	-0.19	10	22
CDC25B	0.024	0.048	-10000	0	-0.51	4	4
SGOL1	-0.039	0.067	0.14	2	-0.14	148	150
RHOA	0.021	0.013	-10000	0	-10000	0	0
CCNB1/CDK1	0.019	0.061	-10000	0	-0.39	6	6
CDC14B	0.01	0.002	-10000	0	-10000	0	0
CDC20	-0.017	0.15	-10000	0	-0.51	42	42
PLK1/PBIP1	-0.009	0.066	0.14	3	-0.3	17	20
mitosis	-0.002	0.003	0.022	1	-10000	0	1
FBXO5	0	0.044	0.19	7	-0.18	4	11
CDC2	0	0.003	-10000	0	-0.015	6	6
NDC80	-0.083	0.22	-10000	0	-0.5	106	106
metaphase plate congression	-0.003	0.061	0.14	3	-0.26	22	25
ERCC6L	0.001	0.087	-10000	0	-0.42	17	17
NLP/gamma Tubulin	0.001	0.029	0.12	8	-0.12	8	16
microtubule cytoskeleton organization	0.003	0.038	0.15	4	-0.2	11	15
G2/M transition DNA damage checkpoint	0	0.002	0.012	2	-10000	0	2
PPP1R12A	0.028	0.005	-10000	0	-10000	0	0
interphase	0	0.002	0.012	2	-10000	0	2
PLK1/PRC1-2	-0.08	0.16	-10000	0	-0.29	172	172
GRASP65/GM130/RAB1/GTP/PLK1	0.021	0.042	-10000	0	-10000	0	0
RAB1A	0.028	0.005	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.002	0.032	0.12	13	-0.11	7	20
mitotic prometaphase	-0.001	0.004	0.017	15	-10000	0	15
proteasomal ubiquitin-dependent protein catabolic process	0.01	0.054	-10000	0	-0.47	3	3
microtubule-based process	-0.09	0.15	0.21	1	-0.3	174	175
Golgi organization	-0.002	0.042	0.15	11	-0.14	7	18
Cohesin/SA2	0.01	0.041	0.17	3	-10000	0	3
PPP1CB/MYPT1	0.041	0.01	-10000	0	-10000	0	0
KIF20A	-0.16	0.25	-10000	0	-0.5	174	174
APC/C/CDC20	-0.01	0.1	0.18	4	-0.33	41	45
PPP2R1A	0.029	0.003	-10000	0	-10000	0	0
chromosome segregation	-0.009	0.065	0.14	3	-0.3	17	20
PRC1	0.023	0.053	-10000	0	-0.5	5	5
ECT2	0.006	0.054	0.24	15	-10000	0	15
C13orf34	0.001	0.033	0.13	11	-0.12	7	18
NUDC	-0.003	0.061	0.14	3	-0.26	22	25
regulation of attachment of spindle microtubules to kinetochore	-0.003	0.072	0.2	8	-0.24	27	35
spindle assembly	0	0.037	0.14	11	-0.12	6	17
spindle stabilization	0.008	0.03	0.15	9	-0.19	1	10
APC/C/HCDH1	0.027	0.02	-10000	0	-0.39	1	1
MKLP2/PLK1	-0.09	0.15	0.21	1	-0.3	174	175
CCNB1	0.019	0.067	-10000	0	-0.51	8	8
PPP1CB	0.029	0.005	-10000	0	-10000	0	0
BTRC	0.028	0.006	-10000	0	-10000	0	0
ROCK2	-0.022	0.074	0.19	2	-0.37	9	11
TUBG1	0.005	0.036	0.15	4	-0.24	6	10
G2/M transition of mitotic cell cycle	-0.007	0.05	-10000	0	-0.38	6	6
MLF1IP	-0.004	0.07	-10000	0	-0.38	17	17
INCENP	0.028	0.003	-10000	0	-10000	0	0

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	-0.12	0.22	-10000	0	-0.62	72	72
NFATC2	-0.067	0.19	-10000	0	-0.67	10	10
NFATC3	-0.018	0.061	-10000	0	-0.33	1	1
CD40LG	-0.17	0.31	-10000	0	-0.88	39	39
ITCH	0.036	0.045	-10000	0	-10000	0	0
CBLB	0.034	0.046	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.28	0.37	-10000	0	-0.89	92	92
JUNB	0.026	0.04	-10000	0	-0.61	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	0.034	0.054	-10000	0	-0.29	11	11
T cell anergy	0.022	0.071	-10000	0	-0.41	10	10
TLE4	-0.034	0.13	-10000	0	-0.53	6	6
Jun/NFAT1-c-4/p21SNFT	-0.11	0.25	-10000	0	-0.98	8	8
AP-1/NFAT1-c-4	-0.16	0.32	-10000	0	-1.1	16	16
IKZF1	-0.08	0.22	-10000	0	-0.53	86	86
T-helper 2 cell differentiation	-0.26	0.24	0.49	2	-0.65	60	62
AP-1/NFAT1	-0.046	0.16	-10000	0	-0.54	11	11
CALM1	0.034	0.034	-10000	0	-10000	0	0
EGR2	-0.08	0.22	-10000	0	-1.3	8	8
EGR3	-0.08	0.21	-10000	0	-1.3	7	7
NFAT1/FOXP3	-0.15	0.28	-10000	0	-0.67	85	85
EGR1	0.013	0.08	-10000	0	-0.61	8	8
JUN	0.01	0.031	-10000	0	-10000	0	0
EGR4	0.021	0.048	-10000	0	-0.5	4	4
mol:Ca2+	-0.002	0.038	-10000	0	-0.32	3	3
GBP3	-0.037	0.14	-10000	0	-0.59	8	8
FOSL1	0.004	0.11	-10000	0	-0.5	24	24
NFAT1-c-4/MAF/IRF4	-0.12	0.27	-10000	0	-0.87	12	12
DGKA	-0.035	0.14	-10000	0	-0.66	8	8
CREM	0.028	0.004	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.088	0.2	-10000	0	-1	6	6
CTLA4	-0.24	0.34	-10000	0	-0.62	200	200
NFAT1-c-4 (dimer)/EGR1	-0.071	0.21	-10000	0	-1.1	6	6
NFAT1-c-4 (dimer)/EGR4	-0.076	0.22	-10000	0	-0.94	8	8
FOS	-0.006	0.098	-10000	0	-0.6	12	12
IFNG	-0.23	0.29	-10000	0	-0.64	121	121
T cell activation	-0.04	0.16	0.46	1	-0.69	6	7
MAF	0.028	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	0.052	0.14	0.78	5	-10000	0	5
TNF	-0.055	0.21	-10000	0	-1.1	6	6
FASLG	-0.18	0.3	-10000	0	-1.3	9	9
TBX21	-0.18	0.26	-10000	0	-0.55	167	167
BATF3	-0.018	0.15	-10000	0	-0.5	44	44
PRKCQ	-0.023	0.098	-10000	0	-0.55	14	14
PTPN1	-0.033	0.13	-10000	0	-0.53	6	6
NFAT1-c-4/ICER1	-0.075	0.21	-10000	0	-0.92	8	8
GATA3	-0.28	0.32	-10000	0	-0.61	245	245
T-helper 1 cell differentiation	-0.22	0.29	-10000	0	-0.62	122	122
IL2RA	-0.19	0.31	-10000	0	-0.8	69	69
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.033	0.13	-10000	0	-0.53	6	6
E2F1	-0.021	0.16	-10000	0	-0.5	52	52
PPARG	0.02	0.013	-10000	0	-10000	0	0
SLC3A2	-0.033	0.13	-10000	0	-0.53	6	6
IRF4	-0.096	0.22	-10000	0	-0.51	118	118
PTGS2	-0.16	0.29	-10000	0	-0.94	23	23
CSF2	-0.15	0.27	-10000	0	-0.98	19	19
JunB/Fra1/NFAT1-c-4	-0.072	0.22	-10000	0	-0.96	6	6
IL4	-0.27	0.25	0.49	2	-0.69	53	55
IL5	-0.14	0.26	-10000	0	-0.96	13	13
IL2	-0.04	0.16	0.46	1	-0.7	6	7
IL3	-0.026	0.058	-10000	0	-0.9	1	1
RNF128	0.023	0.12	-10000	0	-0.6	16	16
NFATC1	-0.052	0.15	-10000	0	-0.79	5	5
CDK4	0.038	0.12	0.54	1	-10000	0	1
PTPRK	-0.036	0.13	-10000	0	-0.53	6	6
IL8	-0.16	0.3	-10000	0	-0.96	26	26
POU2F1	0.028	0.006	-10000	0	-10000	0	0

S1P1 pathway

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
VEGFR2 homodimer/VEGFA homodimer	-0.14	0.2	-10000	0	-0.36	228	228
PDGFRB	0.022	0.013	-10000	0	-10000	0	0
SPHK1	-0.007	0.076	-10000	0	-0.6	6	6
mol:S1P	-0.003	0.07	-10000	0	-0.5	6	6
S1P1/S1P/Gi	-0.047	0.12	0.32	1	-0.45	20	21
GNAO1	0.025	0.05	-10000	0	-0.53	4	4
PDGFB-D/PDGFRB/PLCgamma1	-0.026	0.1	0.33	1	-0.43	11	12
PLCG1	-0.038	0.11	0.32	2	-0.44	16	18
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.022	0.013	-10000	0	-10000	0	0
GNAI2	0.021	0.015	-10000	0	-10000	0	0
GNAI3	0.028	0.008	-10000	0	-10000	0	0
GNAI1	0.025	0.03	-10000	0	-0.62	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	-0.13	0.16	0.18	1	-0.3	227	228
S1P1/S1P	-0.075	0.13	0.25	1	-0.33	23	24
negative regulation of cAMP metabolic process	-0.046	0.12	0.32	1	-0.44	20	21
MAPK3	-0.048	0.14	0.42	2	-0.58	23	25
calcium-dependent phospholipase C activity	0	0.002	-10000	0	-10000	0	0
Rac1/GDP	0.019	0.007	-10000	0	-10000	0	0
RhoA/GDP	0.015	0.01	-10000	0	-10000	0	0
KDR	0.027	0.029	-10000	0	-0.61	1	1
PLCB2	-0.085	0.15	0.31	10	-0.37	50	60
RAC1	0.026	0.009	-10000	0	-10000	0	0
RhoA/GTP	-0.074	0.099	-10000	0	-0.29	20	20
receptor internalization	-0.074	0.12	-10000	0	-0.31	24	24
PTGS2	-0.049	0.23	0.45	8	-0.94	24	32
Rac1/GTP	-0.067	0.1	-10000	0	-0.29	21	21
RHOA	0.021	0.013	-10000	0	-10000	0	0
VEGFA	-0.21	0.26	-10000	0	-0.5	228	228
negative regulation of T cell proliferation	-0.046	0.12	0.32	1	-0.44	20	21
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	0.025	0.05	-10000	0	-0.61	3	3
MAPK1	-0.05	0.15	0.32	1	-0.58	25	26
S1P1/S1P/PDGFB-D/PDGFRB	-0.067	0.12	0.29	1	-0.34	12	13
ABCC1	0.028	0.007	-10000	0	-10000	0	0

Glucocorticoid receptor regulatory network

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
PCK2	0.033	0.083	-10000	0	-1.1	1	1
SMARCC2	0.03	0.005	-10000	0	-10000	0	0
SMARCC1	0.022	0.014	-10000	0	-10000	0	0
TBX21	-0.16	0.23	0.54	1	-0.47	169	170
SUMO2	0.022	0.013	-10000	0	-10000	0	0
STAT1 (dimer)	0.034	0.032	-10000	0	-0.68	1	1
FKBP4	0.028	0.006	-10000	0	-10000	0	0
FKBP5	0.02	0.064	-10000	0	-0.52	7	7
GR alpha/HSP90/FKBP51/HSP90	0.061	0.091	0.33	7	-0.35	2	9
PRL	-0.027	0.1	-10000	0	-0.65	4	4
cortisol/GR alpha (dimer)/TIF2	0.12	0.21	0.51	51	-0.41	2	53
RELA	0.008	0.079	-10000	0	-0.3	1	1
FGG	-0.027	0.25	0.46	16	-0.44	63	79
GR beta/TIF2	0.046	0.1	0.33	7	-0.42	5	12
IFNG	-0.26	0.26	-10000	0	-0.6	123	123
apoptosis	-0.083	0.21	-10000	0	-0.53	55	55
CREB1	-0.004	0.1	-10000	0	-0.35	40	40
histone acetylation	-0.005	0.094	0.27	3	-0.38	7	10
BGLAP	-0.018	0.089	-10000	0	-0.52	3	3
GR/PKAc	0.07	0.086	0.36	3	-10000	0	3
NF kappa B1 p50/RelA	0.013	0.14	-10000	0	-0.45	23	23
SMARCD1	0.03	0.005	-10000	0	-10000	0	0
MDM2	0.035	0.073	0.26	10	-10000	0	10
GATA3	-0.27	0.32	-10000	0	-0.6	245	245
AKT1	0.02	0.008	-10000	0	-10000	0	0
CSF2	-0.024	0.095	-10000	0	-0.57	4	4
GSK3B	0.022	0.013	-10000	0	-10000	0	0
NR1I3	-0.048	0.22	-10000	0	-0.66	20	20
CSN2	0.061	0.15	0.37	21	-10000	0	21
BRG1/BAF155/BAF170/BAF60A	0.057	0.038	-10000	0	-10000	0	0
NFATC1	0.029	0.006	-10000	0	-10000	0	0
POU2F1	0.03	0.008	-10000	0	-10000	0	0
CDKN1A	0.03	0.058	0.86	1	-10000	0	1
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.003	0.006	-10000	0	-10000	0	0
SFN	-0.036	0.18	-10000	0	-0.52	59	59
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.033	0.13	0.34	3	-0.37	10	13
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.021	0.24	-10000	0	-0.66	19	19
JUN	-0.18	0.2	-10000	0	-0.53	78	78
IL4	-0.026	0.084	-10000	0	-0.5	1	1
CDK5R1	0.026	0.006	-10000	0	-10000	0	0
PRKACA	0.029	0.002	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.16	0.2	0.25	12	-0.47	92	104
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.07	0.092	0.36	4	-0.35	1	5
cortisol/GR alpha (monomer)	0.12	0.24	0.57	56	-10000	0	56
NCOA2	0.017	0.08	-10000	0	-0.61	8	8
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.042	0.11	-10000	0	-0.65	12	12
AP-1/NFAT1-c-4	-0.24	0.25	-10000	0	-0.64	82	82
AFP	-0.33	0.52	-10000	0	-1.3	106	106
SUV420H1	0.029	0.003	-10000	0	-10000	0	0
IRF1	0.059	0.1	0.45	5	-10000	0	5
TP53	0.047	0.016	-10000	0	-10000	0	0
PPP5C	0.029	0.003	-10000	0	-10000	0	0
KRT17	-0.2	0.32	-10000	0	-0.94	61	61
KRT14	-0.098	0.16	-10000	0	-0.57	18	18
TBP	0.034	0.013	-10000	0	-10000	0	0
CREBBP	0.047	0.048	-10000	0	-10000	0	0
HDAC1	0.026	0.006	-10000	0	-10000	0	0
HDAC2	0.027	0.01	-10000	0	-10000	0	0
AP-1	-0.24	0.25	-10000	0	-0.64	83	83
MAPK14	0.024	0.011	-10000	0	-10000	0	0
MAPK10	0.018	0.064	-10000	0	-0.62	5	5
MAPK11	0.022	0.027	-10000	0	-0.52	1	1
KRT5	-0.18	0.23	-10000	0	-0.62	69	69
interleukin-1 receptor activity	0	0.007	-10000	0	-10000	0	0
NCOA1	0.03	0.007	-10000	0	-10000	0	0
STAT1	0.034	0.032	-10000	0	-0.68	1	1
CGA	-0.12	0.32	-10000	0	-1.1	48	48
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.069	0.1	0.4	13	-10000	0	13
MAPK3	0.024	0.01	-10000	0	-10000	0	0
MAPK1	0.024	0.01	-10000	0	-10000	0	0
ICAM1	-0.05	0.17	-10000	0	-0.57	30	30
NFKB1	0.007	0.086	-10000	0	-0.34	7	7
MAPK8	-0.11	0.15	-10000	0	-0.42	42	42
MAPK9	0.019	0.012	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.088	0.22	-10000	0	-0.56	57	57
BAX	0.032	0.032	-10000	0	-10000	0	0
POMC	-0.049	0.14	0.48	1	-0.73	6	7
EP300	0.048	0.055	-10000	0	-0.53	1	1
cortisol/GR alpha (dimer)/p53	0.14	0.21	0.52	55	-10000	0	55
proteasomal ubiquitin-dependent protein catabolic process	0.014	0.056	0.22	4	-10000	0	4
SGK1	0.064	0.083	-10000	0	-10000	0	0
IL13	-0.27	0.24	-10000	0	-0.66	86	86
IL6	-0.098	0.29	-10000	0	-0.8	57	57
PRKACG	0.02	0.006	-10000	0	-10000	0	0
IL5	-0.22	0.19	-10000	0	-0.62	35	35
IL2	-0.15	0.19	-10000	0	-0.62	30	30
CDK5	0.024	0.009	-10000	0	-10000	0	0
PRKACB	0.028	0.005	-10000	0	-10000	0	0
HSP90AA1	0.027	0.008	-10000	0	-10000	0	0
IL8	-0.07	0.23	-10000	0	-0.67	43	43
CDK5R1/CDK5	0.034	0.015	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	0.046	0.12	-10000	0	-0.42	7	7
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.13	0.19	0.5	50	-10000	0	50
SMARCA4	0.03	0.003	-10000	0	-10000	0	0
chromatin remodeling	0.063	0.11	0.37	17	-10000	0	17
NF kappa B1 p50/RelA/Cbp	0.064	0.14	-10000	0	-0.47	7	7
JUN (dimer)	-0.18	0.2	-10000	0	-0.53	78	78
YWHAH	0.028	0.004	-10000	0	-10000	0	0
VIPR1	-0.05	0.15	-10000	0	-0.69	17	17
NR3C1	0.059	0.14	0.44	17	-0.52	1	18
NR4A1	0.016	0.11	-10000	0	-0.59	15	15
TIF2/SUV420H1	0.032	0.062	-10000	0	-0.45	8	8
MAPKKK cascade	-0.083	0.21	-10000	0	-0.53	55	55
cortisol/GR alpha (dimer)/Src-1	0.13	0.21	0.51	55	-0.42	1	56
PBX1	0.011	0.11	-10000	0	-0.61	15	15
POU1F1	0.021	0.01	-10000	0	-10000	0	0
SELE	-0.094	0.31	-10000	0	-1	42	42
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.063	0.11	0.38	17	-10000	0	17
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.13	0.19	0.5	50	-10000	0	50
mol:cortisol	0.043	0.15	0.3	58	-0.26	28	86
MMP1	-0.15	0.3	-10000	0	-0.88	54	54

Ceramide signaling 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
SPHK2	0.016	0.037	-10000	0	-0.45	3	3
MAP4K4	0.012	0.058	-10000	0	-0.47	2	2
BAG4	0.025	0.029	-10000	0	-0.61	1	1
PKC zeta/ceramide	-0.099	0.085	-10000	0	-0.3	54	54
NFKBIA	0.027	0.007	-10000	0	-10000	0	0
BIRC3	-0.054	0.19	-10000	0	-0.5	79	79
BAX	-0.035	0.036	-10000	0	-0.3	4	4
RIPK1	0.028	0.005	-10000	0	-10000	0	0
AKT1	0.026	0.069	0.89	3	-10000	0	3
BAD	-0.1	0.079	-10000	0	-0.3	48	48
SMPD1	0.02	0.053	0.27	9	-0.19	5	14
RB1	-0.098	0.079	-10000	0	-0.3	47	47
FADD/Caspase 8	0.018	0.073	-10000	0	-0.43	4	4
MAP2K4	-0.078	0.077	-10000	0	-0.28	36	36
NSMAF	0.027	0.007	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.075	0.086	-10000	0	-0.28	50	50
EGF	-0.54	0.19	-10000	0	-0.61	460	460
mol:ceramide	-0.11	0.084	0.17	2	-0.3	56	58
MADD	0.029	0.003	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.016	0.022	-10000	0	-0.45	1	1
ASAH1	0.026	0.009	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.098	0.078	-10000	0	-0.29	47	47
cell proliferation	-0.058	0.071	-10000	0	-0.39	7	7
BID	-0.005	0.075	-10000	0	-0.57	5	5
MAP3K1	-0.089	0.073	0.18	2	-0.29	37	39
EIF2A	-0.074	0.084	0.29	7	-0.6	3	10
TRADD	0.028	0.006	-10000	0	-10000	0	0
CRADD	0.028	0.005	-10000	0	-10000	0	0
MAPK3	-0.077	0.072	-10000	0	-0.38	10	10
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.077	0.073	-10000	0	-0.43	7	7
Cathepsin D/ceramide	-0.098	0.08	-10000	0	-0.28	54	54
FADD	0.013	0.058	-10000	0	-0.47	2	2
KSR1	-0.1	0.082	0.18	1	-0.29	56	57
MAPK8	-0.08	0.086	-10000	0	-0.3	42	42
PRKRA	-0.096	0.081	0.18	2	-0.29	51	53
PDGFA	0.024	0.03	-10000	0	-0.61	1	1
TRAF2	0.028	0.005	-10000	0	-10000	0	0
IGF1	0.023	0.053	-10000	0	-0.5	5	5
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.11	0.083	0.17	2	-0.3	56	58
CTSD	0.027	0.028	-10000	0	-0.61	1	1
regulation of nitric oxide biosynthetic process	0.041	0.023	-10000	0	-0.45	1	1
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.061	0.077	-10000	0	-0.42	7	7
PRKCD	0.02	0.027	-10000	0	-0.5	1	1
PRKCZ	0.024	0.049	-10000	0	-0.61	3	3
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.016	0.022	-10000	0	-0.45	1	1
RelA/NF kappa B1	0.041	0.023	-10000	0	-0.45	1	1
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.027	0.029	-10000	0	-0.61	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.014	0.062	-10000	0	-0.5	2	2
TNFR1A/BAG4/TNF-alpha	0.044	0.057	-10000	0	-0.35	9	9
mol:Sphingosine-1-phosphate	0.016	0.037	-10000	0	-0.45	3	3
MAP2K1	-0.082	0.075	-10000	0	-0.4	10	10
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.029	0.003	-10000	0	-10000	0	0
CYCS	-0.053	0.035	-10000	0	-0.24	8	8
TNFRSF1A	0.028	0.006	-10000	0	-10000	0	0
NFKB1	0.027	0.029	-10000	0	-0.61	1	1
TNFR1A/BAG4	0.037	0.026	-10000	0	-0.45	1	1
EIF2AK2	-0.085	0.089	0.27	7	-0.28	46	53
TNF-alpha/TNFR1A/FAN	0.045	0.053	-10000	0	-0.35	8	8
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.026	0.07	-10000	0	-0.4	7	7
MAP2K2	-0.083	0.073	-10000	0	-0.4	9	9
SMPD3	0.015	0.051	0.2	3	-0.32	4	7
TNF	0.018	0.073	-10000	0	-0.56	8	8
PKC zeta/PAR4	0.036	0.045	-10000	0	-0.45	4	4
mol:PHOSPHOCHOLINE	0.2	0.086	0.24	413	-10000	0	413
NF kappa B1/RelA/I kappa B alpha	0.072	0.045	-10000	0	-0.33	3	3
AIFM1	-0.06	0.049	-10000	0	-0.28	7	7
BCL2	0.028	0.005	-10000	0	-10000	0	0

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.033	0.049	-10000	0	-0.37	7	7
VEGFR1 homodimer/NRP1	0.013	0.046	-10000	0	-0.37	7	7
mol:DAG	-0.14	0.15	-10000	0	-0.44	15	15
VEGFR1 homodimer/NRP1/VEGFR 121	-0.11	0.16	-10000	0	-0.45	9	9
CaM/Ca2+	-0.12	0.15	-10000	0	-0.57	6	6
HIF1A	0.029	0.046	-10000	0	-0.6	2	2
GAB1	0.028	0.004	-10000	0	-10000	0	0
AKT1	-0.092	0.14	-10000	0	-0.58	6	6
PLCG1	-0.14	0.16	-10000	0	-0.44	15	15
NOS3	-0.08	0.12	-10000	0	-0.46	11	11
CBL	0.027	0.028	-10000	0	-0.61	1	1
mol:NO	-0.074	0.13	0.72	1	-0.44	11	12
FLT1	0.019	0.054	-10000	0	-0.44	7	7
PGF	-0.27	0.27	-10000	0	-0.51	282	282
VEGFR1 homodimer/NRP2/VEGFR121	-0.098	0.17	-10000	0	-0.46	11	11
CALM1	0.027	0.008	-10000	0	-10000	0	0
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
eNOS/Hsp90	-0.063	0.14	0.43	2	-0.49	5	7
endothelial cell proliferation	-0.098	0.13	0.58	1	-0.44	13	14
mol:Ca2+	-0.14	0.15	-10000	0	-0.44	15	15
MAPK3	-0.12	0.14	0.46	2	-0.5	6	8
MAPK1	-0.12	0.14	0.46	2	-0.53	6	8
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
PLGF homodimer	-0.27	0.27	-10000	0	-0.51	282	282
PRKACA	0.029	0.002	-10000	0	-10000	0	0
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	-0.006	0.12	-10000	0	-0.5	30	30
VEGFA homodimer	-0.21	0.26	-10000	0	-0.5	228	228
VEGFR1 homodimer/VEGFA homodimer	-0.12	0.17	-10000	0	-0.49	9	9
platelet activating factor biosynthetic process	-0.12	0.13	0.44	2	-0.49	6	8
PI3K	-0.11	0.16	-10000	0	-0.62	6	6
PRKCA	-0.13	0.14	0.58	1	-0.56	6	7
PRKCB	-0.13	0.14	0.58	1	-0.52	8	9
VEGFR1 homodimer/PLGF homodimer	-0.16	0.18	-10000	0	-0.46	18	18
VEGFA	-0.21	0.26	-10000	0	-0.5	228	228
VEGFB	0.029	0.003	-10000	0	-10000	0	0
mol:IP3	-0.14	0.15	-10000	0	-0.44	15	15
RASA1	0.019	0.05	-10000	0	-0.67	1	1
NRP2	0.02	0.062	-10000	0	-0.5	7	7
VEGFR1 homodimer	0.019	0.054	-10000	0	-0.43	7	7
VEGFB homodimer	0.029	0.003	-10000	0	-10000	0	0
NCK1	0.026	0.029	-10000	0	-0.61	1	1
eNOS/Caveolin-1	-0.084	0.14	-10000	0	-0.44	27	27
PTPN11	0.028	0.005	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.11	0.16	-10000	0	-0.61	6	6
mol:L-citrulline	-0.074	0.13	0.72	1	-0.44	11	12
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.083	0.16	-10000	0	-0.58	5	5
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.098	0.17	-10000	0	-0.57	6	6
CD2AP	0.028	0.006	-10000	0	-10000	0	0
PI3K/GAB1	-0.1	0.16	-10000	0	-0.59	6	6
PDPK1	-0.11	0.15	0.34	1	-0.6	6	7
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.097	0.16	-10000	0	-0.55	5	5
mol:NADP	-0.074	0.13	0.72	1	-0.44	11	12
HSP90AA1	0.027	0.008	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.083	0.16	-10000	0	-0.57	5	5
VEGFR1 homodimer/NRP2	0.028	0.06	-10000	0	-0.37	7	7

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	-0.14	0.2	-10000	0	-0.36	228	228
alphaV beta3 Integrin	0.047	0.06	-10000	0	-0.42	7	7
PTK2	-0.079	0.15	0.51	3	-0.55	6	9
IGF1R	0.029	0.003	-10000	0	-10000	0	0
PI4KB	0.027	0.006	-10000	0	-10000	0	0
MFGE8	0.028	0.024	-10000	0	-0.5	1	1
SRC	0.028	0.006	-10000	0	-10000	0	0
CDKN1B	-0.041	0.17	-10000	0	-0.47	69	69
VEGFA	-0.21	0.26	-10000	0	-0.5	228	228
ILK	-0.042	0.18	-10000	0	-0.47	71	71
ROCK1	0.028	0.004	-10000	0	-10000	0	0
AKT1	-0.041	0.16	-10000	0	-0.44	68	68
PTK2B	-0.095	0.14	0.36	2	-0.56	1	3
alphaV/beta3 Integrin/JAM-A	0.004	0.14	-10000	0	-0.65	1	1
CBL	0.027	0.028	-10000	0	-0.61	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.14	0.21	-10000	0	-0.39	213	213
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.061	0.054	-10000	0	-0.35	4	4
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.084	0.14	-10000	0	-0.4	55	55
alphaV/beta3 Integrin/Syndecan-1	0.047	0.06	-10000	0	-0.39	9	9
PI4KA	0.028	0.004	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.029	0.1	-10000	0	-0.56	4	4
PI4 Kinase	0.04	0.011	-10000	0	-10000	0	0
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
alphaV/beta3 Integrin/Osteopontin	0.049	0.047	-10000	0	-0.39	5	5
RPS6KB1	0.018	0.12	0.47	13	-0.53	4	17
TLN1	0.028	0.006	-10000	0	-10000	0	0
MAPK3	0	0.1	-10000	0	-0.61	7	7
GPR124	0.025	0.025	-10000	0	-0.5	1	1
MAPK1	0.001	0.1	-10000	0	-0.61	7	7
PXN	0.028	0.005	-10000	0	-10000	0	0
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
alphaV/beta3 Integrin/Tumstatin	0.005	0.14	-10000	0	-0.39	54	54
cell adhesion	-0.11	0.18	-10000	0	-0.36	23	23
ANGPTL3	-0.25	0.31	-10000	0	-0.59	232	232
VEGFR2 homodimer/VEGFA homodimer/Src	-0.11	0.18	-10000	0	-0.31	224	224
IGF-1R heterotetramer	0.029	0.003	-10000	0	-10000	0	0
Rac1/GDP	0.019	0.007	-10000	0	-10000	0	0
TGFBR2	0.021	0.013	-10000	0	-10000	0	0
ITGB3	0.024	0.049	-10000	0	-0.61	3	3
IGF1	0.023	0.053	-10000	0	-0.5	5	5
RAC1	0.026	0.009	-10000	0	-10000	0	0
regulation of cell-matrix adhesion	0.047	0.039	-10000	0	-0.38	3	3
apoptosis	0.027	0.006	-10000	0	-10000	0	0
CD47	0.026	0.008	-10000	0	-10000	0	0
alphaV/beta3 Integrin/CD47	0.048	0.039	-10000	0	-0.39	3	3
VCL	0.028	0.005	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Del1	0.037	0.076	-10000	0	-0.38	14	14
CSF1	0.027	0.029	-10000	0	-0.61	1	1
PIK3C2A	-0.044	0.18	-10000	0	-0.48	72	72
PI4 Kinase/Pyk2	-0.12	0.17	-10000	0	-0.5	39	39
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.085	0.17	-10000	0	-0.4	5	5
FAK1/Vinculin	-0.056	0.14	0.59	3	-0.49	3	6
alphaV beta3/Integrin/ppsTEM5	0.048	0.04	-10000	0	-0.39	3	3
RHOA	0.021	0.013	-10000	0	-10000	0	0
VTN	-0.065	0.22	-10000	0	-0.59	76	76
BCAR1	0.027	0.029	-10000	0	-0.61	1	1
FGF2	0.022	0.061	-10000	0	-0.59	5	5
F11R	0.016	0.042	-10000	0	-0.45	4	4
alphaV/beta3 Integrin/Lactadherin	0.051	0.04	-10000	0	-0.37	4	4
alphaV/beta3 Integrin/TGFBR2	0.038	0.042	-10000	0	-0.38	3	3
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.065	0.044	-10000	0	-0.52	2	2
HSP90AA1	0.027	0.008	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	0.048	0.035	-10000	0	-0.35	3	3
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	-0.012	0.14	-10000	0	-0.51	37	37
alphaV/beta3 Integrin/Pyk2	-0.085	0.15	-10000	0	-0.39	4	4
SDC1	0.02	0.069	-10000	0	-0.61	6	6
VAV3	0.026	0.083	0.36	7	-0.64	1	8
PTPN11	0.028	0.005	-10000	0	-10000	0	0
IRS1	0.022	0.057	-10000	0	-0.61	4	4
FAK1/Paxillin	-0.057	0.13	0.53	2	-0.44	5	7
cell migration	-0.053	0.12	0.52	2	-0.44	3	5
ITGAV	0.027	0.006	-10000	0	-10000	0	0
PI3K	0.013	0.13	-10000	0	-0.88	1	1
SPP1	0.025	0.049	-10000	0	-0.61	3	3
KDR	0.027	0.029	-10000	0	-0.61	1	1
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.027	0.006	-10000	0	-10000	0	0
COL4A3	-0.041	0.2	-10000	0	-0.58	57	57
angiogenesis	-0.008	0.13	0.31	4	-0.63	7	11
Rac1/GTP	0.031	0.063	-10000	0	-0.59	1	1
EDIL3	0.011	0.092	-10000	0	-0.55	13	13
cell proliferation	0.037	0.042	-10000	0	-0.38	3	3

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.012	0.14	0.37	13	-0.46	10	23
IKBKB	0.01	0.12	0.33	19	-0.3	5	24
AKT1	0.005	0.13	0.39	27	-0.26	6	33
IKBKG	0.024	0.1	0.32	15	-0.28	1	16
CALM1	0.003	0.082	0.36	1	-0.31	4	5
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
MAP3K1	-0.029	0.17	0.38	21	-0.42	23	44
MAP3K7	0.027	0.007	-10000	0	-10000	0	0
mol:Ca2+	0.004	0.087	0.26	1	-0.33	4	5
DOK1	0.028	0.005	-10000	0	-10000	0	0
AP-1	0.017	0.1	0.29	22	-0.27	8	30
LYN	0.027	0.007	-10000	0	-10000	0	0
BLNK	0.026	0.029	-10000	0	-0.61	1	1
SHC1	0.027	0.006	-10000	0	-10000	0	0
BCR complex	-0.058	0.18	-10000	0	-0.37	122	122
CD22	-0.05	0.13	-10000	0	-0.42	27	27
CAMK2G	0.009	0.081	0.35	1	-10000	0	1
CSNK2A1	0.028	0.005	-10000	0	-10000	0	0
INPP5D	0.023	0.047	-10000	0	-0.5	4	4
SHC/GRB2/SOS1	-0.031	0.12	-10000	0	-0.45	3	3
GO:0007205	0.003	0.088	0.26	1	-0.33	4	5
SYK	0.026	0.032	-10000	0	-0.46	2	2
ELK1	0.007	0.087	0.3	1	-0.32	3	4
NFATC1	-0.03	0.13	0.37	7	-0.34	18	25
B-cell antigen/BCR complex	-0.058	0.18	-10000	0	-0.37	122	122
PAG1/CSK	0.04	0.011	-10000	0	-10000	0	0
NFKBIB	0.021	0.051	0.16	19	-0.13	8	27
HRAS	0.004	0.084	0.29	3	-0.33	1	4
NFKBIA	0.022	0.05	0.16	19	-0.12	5	24
NF-kappa-B/RelA/I kappa B beta	0.027	0.047	0.16	19	-0.17	1	20
RasGAP/Csk	-0.059	0.2	-10000	0	-0.51	46	46
mol:GDP	0.004	0.085	0.27	2	-0.35	4	6
PTEN	0.028	0.006	-10000	0	-10000	0	0
CD79B	0.025	0.041	-10000	0	-0.5	3	3
NF-kappa-B/RelA/I kappa B alpha	0.027	0.047	0.16	19	-0.17	1	20
GRB2	0.028	0.005	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.003	0.16	0.39	15	-0.45	8	23
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
mol:IP3	0.002	0.086	0.26	2	-0.33	5	7
CSK	0.029	0.003	-10000	0	-10000	0	0
FOS	0.001	0.098	0.32	3	-0.51	3	6
CHUK	0.016	0.11	0.32	15	-0.31	9	24
IBTK	0.027	0.007	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.012	0.14	0.39	1	-0.41	4	5
PTPN6	-0.046	0.12	-10000	0	-0.5	12	12
RELA	0.029	0.003	-10000	0	-10000	0	0
BCL2A1	0.006	0.054	0.15	12	-0.14	1	13
VAV2	-0.059	0.16	-10000	0	-0.45	42	42
ubiquitin-dependent protein catabolic process	0.025	0.05	0.15	22	-0.12	5	27
BTK	-0.03	0.14	-10000	0	-0.89	11	11
CD19	-0.072	0.17	-10000	0	-0.46	64	64
MAP4K1	-0.19	0.26	-10000	0	-0.5	207	207
CD72	-0.1	0.23	-10000	0	-0.51	122	122
PAG1	0.027	0.007	-10000	0	-10000	0	0
MAPK14	-0.02	0.16	0.37	21	-0.38	9	30
SH3BP5	0.019	0.031	-10000	0	-0.61	1	1
PIK3AP1	0.008	0.087	0.3	1	-0.43	3	4
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.046	0.12	-10000	0	-0.4	13	13
RAF1	0	0.079	0.31	3	-10000	0	3
RasGAP/p62DOK/SHIP	-0.058	0.19	-10000	0	-0.5	47	47
CD79A	-0.1	0.23	-10000	0	-0.5	124	124
re-entry into mitotic cell cycle	0.017	0.1	0.29	22	-0.28	6	28
RASA1	0.024	0.03	-10000	0	-0.61	1	1
MAPK3	0.021	0.095	0.34	14	-10000	0	14
MAPK1	0.017	0.086	0.34	7	-10000	0	7
CD72/SHP1	-0.085	0.2	0.35	1	-0.48	61	62
NFKB1	0.027	0.029	-10000	0	-0.61	1	1
MAPK8	-0.022	0.16	0.37	22	-0.38	9	31
actin cytoskeleton organization	-0.036	0.16	0.33	8	-0.4	35	43
NF-kappa-B/RelA	0.056	0.085	0.29	19	-10000	0	19
Calcineurin	0.027	0.081	-10000	0	-10000	0	0
PI3K	-0.062	0.14	-10000	0	-0.42	39	39
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	0	0.083	0.31	1	-0.4	4	5
SOS1	0.028	0.005	-10000	0	-10000	0	0
Bam32/HPK1	-0.11	0.2	-10000	0	-0.53	30	30
DAPP1	-0.03	0.14	-10000	0	-0.66	13	13
cytokine secretion	-0.027	0.13	0.36	7	-0.32	17	24
mol:DAG	0.002	0.086	0.26	2	-0.33	5	7
PLCG2	0.02	0.068	-10000	0	-0.55	7	7
MAP2K1	0.014	0.086	0.33	6	-10000	0	6
B-cell antigen/BCR complex/FcgammaRIIB	-0.088	0.22	-10000	0	-0.39	161	161
mol:PI-3-4-5-P3	-0.049	0.1	-10000	0	-0.32	28	28
ETS1	0.012	0.082	0.43	2	-10000	0	2
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.01	0.15	-10000	0	-0.42	6	6
B-cell antigen/BCR complex/LYN	-0.049	0.11	-10000	0	-0.36	19	19
MALT1	0.028	0.005	-10000	0	-10000	0	0
TRAF6	0.029	0.003	-10000	0	-10000	0	0
RAC1	-0.042	0.16	0.31	4	-0.42	35	39
B-cell antigen/BCR complex/LYN/SYK	-0.042	0.16	-10000	0	-0.45	27	27
CARD11	-0.026	0.16	0.32	14	-0.34	54	68
FCGR2B	-0.066	0.2	-10000	0	-0.5	89	89
PPP3CA	0.028	0.004	-10000	0	-10000	0	0
BCL10	0.028	0.005	-10000	0	-10000	0	0
IKK complex	0.021	0.069	0.21	31	-10000	0	31
PTPRC	-0.028	0.16	-10000	0	-0.5	53	53
PDPK1	-0.017	0.1	0.3	13	-0.26	9	22
PPP3CB	0.028	0.005	-10000	0	-10000	0	0
PPP3CC	0.026	0.009	-10000	0	-10000	0	0
POU2F2	0.013	0.049	0.15	12	-10000	0	12

IL23-mediated signaling events

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
CCL2	-0.15	0.33	-10000	0	-1.1	12	12
IL23A	-0.13	0.33	-10000	0	-1.1	9	9
NF kappa B1 p50/RelA/I kappa B alpha	-0.13	0.32	-10000	0	-0.99	15	15
positive regulation of T cell mediated cytotoxicity	-0.16	0.34	-10000	0	-1	22	22
ITGA3	-0.14	0.32	-10000	0	-1	10	10
IL17F	-0.092	0.25	0.66	2	-0.71	9	11
IL12B	-0.049	0.16	-10000	0	-0.52	52	52
STAT1 (dimer)	-0.15	0.33	-10000	0	-1	19	19
CD4	-0.14	0.32	-10000	0	-1	14	14
IL23	-0.16	0.3	-10000	0	-1	16	16
IL23R	-0.019	0.15	-10000	0	-0.81	8	8
IL1B	-0.14	0.33	-10000	0	-1	13	13
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.14	0.32	-10000	0	-0.95	17	17
TYK2	0.012	0.034	-10000	0	-10000	0	0
STAT4	-0.003	0.12	-10000	0	-0.5	29	29
STAT3	0.028	0.004	-10000	0	-10000	0	0
IL18RAP	-0.12	0.23	-10000	0	-0.52	132	132
IL12RB1	-0.15	0.26	-10000	0	-0.53	158	158
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
IL12Rbeta1/TYK2	-0.097	0.2	-10000	0	-0.39	158	158
IL23R/JAK2	-0.022	0.15	-10000	0	-0.8	6	6
positive regulation of chronic inflammatory response	-0.16	0.34	-10000	0	-1	22	22
natural killer cell activation	0.002	0.009	0.044	9	-10000	0	9
JAK2	0.008	0.039	-10000	0	-10000	0	0
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
NFKB1	0.027	0.029	-10000	0	-0.61	1	1
RELA	0.028	0.004	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.16	0.3	-10000	0	-0.95	17	17
ALOX12B	-0.17	0.33	-10000	0	-1	17	17
CXCL1	-0.18	0.37	-10000	0	-1.1	35	35
T cell proliferation	-0.16	0.34	-10000	0	-1	22	22
NFKBIA	0.027	0.008	-10000	0	-10000	0	0
IL17A	-0.068	0.21	-10000	0	-0.58	5	5
PI3K	-0.14	0.32	-10000	0	-1	15	15
IFNG	-0.035	0.053	0.11	8	-0.1	61	69
STAT3 (dimer)	-0.13	0.31	-10000	0	-0.98	14	14
IL18R1	0.012	0.068	-10000	0	-0.55	7	7
IL23/IL23R/JAK2/TYK2/SOCS3	-0.089	0.24	-10000	0	-0.7	12	12
IL18/IL18R	-0.078	0.17	-10000	0	-0.34	137	137
macrophage activation	-0.011	0.016	-10000	0	-0.044	6	6
TNF	-0.15	0.33	-10000	0	-1.1	15	15
STAT3/STAT4	-0.15	0.34	-10000	0	-1	21	21
STAT4 (dimer)	-0.16	0.35	-10000	0	-1	23	23
IL18	0.016	0.053	-10000	0	-0.5	5	5
IL19	-0.14	0.32	-10000	0	-0.97	14	14
STAT5A (dimer)	-0.15	0.33	-10000	0	-1	19	19
STAT1	0.026	0.024	-10000	0	-0.5	1	1
SOCS3	0.026	0.034	-10000	0	-0.5	2	2
CXCL9	-0.22	0.37	-10000	0	-0.92	42	42
MPO	-0.15	0.32	-10000	0	-1	14	14
positive regulation of humoral immune response	-0.16	0.34	-10000	0	-1	22	22
IL23/IL23R/JAK2/TYK2	-0.17	0.34	-10000	0	-1.1	18	18
IL6	-0.17	0.4	-10000	0	-1.1	41	41
STAT5A	0.028	0.004	-10000	0	-10000	0	0
IL2	-0.01	0.075	-10000	0	-0.51	10	10
positive regulation of tyrosine phosphorylation of STAT protein	0.002	0.009	0.044	9	-10000	0	9
CD3E	-0.21	0.37	-10000	0	-0.93	37	37
keratinocyte proliferation	-0.16	0.34	-10000	0	-1	22	22
NOS2	-0.14	0.32	-10000	0	-0.99	13	13

Signaling events mediated by PTP1B

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
PDGFRB	0.022	0.012	-10000	0	-10000	0	0
Jak2/Leptin Receptor	-0.065	0.13	-10000	0	-0.43	30	30
PTP1B/AKT1	-0.053	0.072	0.21	1	-0.33	5	6
FYN	0.027	0.008	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.067	0.076	0.37	1	-0.31	10	11
EGFR	-0.015	0.059	-10000	0	-0.54	6	6
EGF/EGFR	-0.29	0.13	-10000	0	-0.35	395	395
CSF1	0.027	0.029	-10000	0	-0.61	1	1
AKT1	0.027	0.008	-10000	0	-10000	0	0
INSR	0.029	0.004	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.068	0.085	-10000	0	-0.38	14	14
Insulin Receptor/Insulin	-0.043	0.077	0.3	1	-10000	0	1
HCK	0.001	0.12	-10000	0	-0.5	26	26
CRK	0.028	0.005	-10000	0	-10000	0	0
TYK2	-0.062	0.073	0.28	2	-0.36	4	6
EGF	-0.55	0.2	-10000	0	-0.61	457	457
YES1	0.028	0.004	-10000	0	-10000	0	0
CAV1	-0.14	0.11	0.33	5	-0.34	26	31
TXN	0.022	0.006	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.056	0.08	0.33	1	-0.38	8	9
cell migration	0.067	0.076	0.31	10	-0.37	1	11
STAT3	0.028	0.004	-10000	0	-10000	0	0
PRLR	-0.049	0.2	-10000	0	-0.61	59	59
ITGA2B	0.009	0.099	-10000	0	-0.51	18	18
CSF1R	0.017	0.053	-10000	0	-0.5	5	5
Prolactin Receptor/Prolactin	-0.026	0.16	-10000	0	-0.46	59	59
FGR	0.025	0.041	-10000	0	-0.5	3	3
PTP1B/p130 Cas	-0.06	0.072	-10000	0	-0.34	5	5
Crk/p130 Cas	-0.055	0.072	-10000	0	-0.34	4	4
DOK1	-0.029	0.082	0.28	5	-0.32	4	9
JAK2	-0.07	0.14	0.32	1	-0.42	42	43
Jak2/Leptin Receptor/Leptin	-0.045	0.1	-10000	0	-0.41	2	2
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
PTPN1	-0.067	0.076	0.37	1	-0.32	10	11
LYN	0.027	0.007	-10000	0	-10000	0	0
CDH2	0.011	0.1	-10000	0	-0.59	14	14
SRC	0.001	0.044	0.34	1	-0.66	1	2
ITGB3	0.024	0.049	-10000	0	-0.61	3	3
CAT1/PTP1B	-0.21	0.15	0.37	6	-0.43	71	77
CAPN1	0.027	0.003	-10000	0	-10000	0	0
CSK	0.029	0.003	-10000	0	-10000	0	0
PI3K	-0.003	0.085	-10000	0	-0.54	1	1
mol:H2O2	-0.006	0.003	-10000	0	-10000	0	0
STAT3 (dimer)	-0.037	0.098	-10000	0	-0.41	2	2
negative regulation of transcription	-0.069	0.14	0.32	1	-0.41	43	44
FCGR2A	0.004	0.11	-10000	0	-0.5	22	22
FER	0.016	0.041	-10000	0	-0.62	2	2
alphaIIb/beta3 Integrin	0.022	0.084	-10000	0	-0.38	21	21
BLK	-0.009	0.13	-10000	0	-0.5	33	33
Insulin Receptor/Insulin/Shc	0.048	0.013	-10000	0	-10000	0	0
RHOA	0.019	0.013	-10000	0	-10000	0	0
LEPR	0.028	0.006	-10000	0	-10000	0	0
BCAR1	0.027	0.029	-10000	0	-0.61	1	1
p210 bcr-abl/Grb2	0.028	0.005	-10000	0	-10000	0	0
mol:NADPH	-0.006	0.003	-10000	0	-10000	0	0
TRPV6	-0.19	0.16	0.36	4	-0.44	75	79
PRL	0.001	0.022	-10000	0	-10000	0	0
SOCS3	0.025	0.11	-10000	0	-0.98	6	6
SPRY2	0.024	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.044	0.042	-10000	0	-0.4	4	4
CSF1/CSF1R	-0.049	0.073	0.33	1	-0.45	3	4
Ras protein signal transduction	0.033	0.071	0.5	10	-10000	0	10
IRS1	0.022	0.057	-10000	0	-0.61	4	4
INS	0.006	0.019	-10000	0	-10000	0	0
LEP	-0.032	0.15	-10000	0	-0.5	46	46
STAT5B	-0.061	0.093	0.36	1	-0.34	24	25
STAT5A	-0.061	0.093	0.36	1	-0.34	24	25
GRB2	0.028	0.005	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.049	0.068	0.33	1	-0.36	3	4
CSN2	0.004	0.071	-10000	0	-0.61	1	1
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
LAT	-0.045	0.092	-10000	0	-0.45	8	8
YBX1	0.031	0.007	-10000	0	-10000	0	0
LCK	0.004	0.11	-10000	0	-0.51	22	22
SHC1	0.027	0.006	-10000	0	-10000	0	0
NOX4	0.02	0.051	-10000	0	-0.54	4	4

IL2 signaling events mediated by PI3K

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
BCL2L1	-0.05	0.13	-10000	0	-0.49	3	3
UGCG	-0.011	0.11	-10000	0	-0.57	19	19
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.025	0.14	0.32	4	-0.44	15	19
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.01	0.11	-10000	0	-0.56	19	19
mol:DAG	-0.013	0.13	-10000	0	-0.84	12	12
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.016	0.13	0.28	1	-0.42	7	8
FRAP1	-0.025	0.14	0.36	3	-0.46	9	12
FOXO3	-0.023	0.14	0.36	4	-0.47	7	11
AKT1	-0.029	0.14	0.3	1	-0.44	21	22
GAB2	0.029	0.003	-10000	0	-10000	0	0
SMPD1	0.009	0.043	-10000	0	-0.74	1	1
SGMS1	-0.006	0.11	-10000	0	-0.7	12	12
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	0.011	0.026	-10000	0	-0.38	2	2
CALM1	0.027	0.008	-10000	0	-10000	0	0
cell proliferation	-0.01	0.12	0.29	4	-0.49	16	20
EIF3A	0.028	0.006	-10000	0	-10000	0	0
PI3K	0.039	0.035	-10000	0	-0.45	2	2
RPS6KB1	-0.014	0.11	-10000	0	-0.91	6	6
mol:sphingomyelin	-0.013	0.13	-10000	0	-0.84	12	12
natural killer cell activation	0	0.001	-10000	0	-10000	0	0
JAK3	-0.077	0.21	-10000	0	-0.5	103	103
PIK3R1	0.027	0.03	-10000	0	-0.61	1	1
JAK1	0.03	0.006	-10000	0	-10000	0	0
NFKB1	0.027	0.029	-10000	0	-0.61	1	1
MYC	-0.019	0.14	0.42	4	-0.53	4	8
MYB	-0.078	0.18	-10000	0	-0.46	24	24
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.04	0.14	0.26	1	-0.43	30	31
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.009	0.12	-10000	0	-0.86	6	6
mol:PI-3-4-5-P3	-0.038	0.14	0.26	1	-0.42	30	31
Rac1/GDP	0.025	0.027	-10000	0	-0.35	2	2
T cell proliferation	-0.033	0.13	0.27	2	-0.43	20	22
SHC1	0.028	0.007	-10000	0	-10000	0	0
RAC1	0.026	0.009	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	-0.006	0.018	-10000	0	-0.036	139	139
PRKCZ	-0.035	0.14	0.25	1	-0.45	20	21
NF kappa B1 p50/RelA	-0.005	0.14	0.3	1	-0.44	5	6
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.064	0.13	-10000	0	-0.39	46	46
HSP90AA1	0.027	0.008	-10000	0	-10000	0	0
RELA	0.029	0.003	-10000	0	-10000	0	0
IL2RA	-0.076	0.21	-10000	0	-0.5	100	100
IL2RB	-0.25	0.27	-10000	0	-0.5	270	270
TERT	-0.04	0.17	-10000	0	-0.51	59	59
E2F1	-0.038	0.12	-10000	0	-0.33	26	26
SOS1	0.028	0.005	-10000	0	-10000	0	0
RPS6	0.026	0.034	-10000	0	-0.5	2	2
mol:cAMP	0.003	0.009	0.017	137	-10000	0	137
PTPN11	0.028	0.006	-10000	0	-10000	0	0
IL2RG	-0.005	0.13	-10000	0	-0.51	34	34
actin cytoskeleton organization	-0.033	0.13	0.27	2	-0.43	20	22
GRB2	0.028	0.005	-10000	0	-10000	0	0
IL2	0.016	0.074	-10000	0	-0.5	10	10
PIK3CA	0.028	0.029	-10000	0	-0.61	1	1
Rac1/GTP	0.045	0.035	-10000	0	-0.33	2	2
LCK	0.007	0.11	-10000	0	-0.51	22	22
BCL2	-0.013	0.12	0.44	2	-0.45	1	3

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.039	0.15	-9999	-0.42	44	44
FZD6	0.027	0.007	-9999	-10000	0	0
WNT6	0.009	0.097	-9999	-0.51	17	17
WNT4	-0.042	0.2	-9999	-0.59	57	57
FZD3	0.026	0.009	-9999	-10000	0	0
WNT5A	0.018	0.037	-9999	-0.41	3	3
WNT11	-0.017	0.16	-9999	-0.6	37	37

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	0.024	0.047	-9999	-0.57	3	3
GNB1/GNG2	-0.028	0.15	-9999	-0.45	24	24
mol:DAG	-0.036	0.13	-9999	-0.42	22	22
PLCG1	-0.037	0.13	-9999	-0.44	22	22
YES1	-0.038	0.14	-9999	-0.4	42	42
FZD3	0.026	0.009	-9999	-10000	0	0
FZD6	0.027	0.007	-9999	-10000	0	0
G protein	-0.025	0.14	-9999	-0.44	22	22
MAP3K7	-0.089	0.16	-9999	-0.46	41	41
mol:Ca2+	-0.035	0.12	-9999	-0.41	22	22
mol:IP3	-0.036	0.13	-9999	-0.42	22	22
NLK	-0.002	0.09	-9999	-0.82	6	6
GNB1	0.028	0.006	-9999	-10000	0	0
CAMK2A	-0.096	0.18	-9999	-0.46	60	60
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.039	0.15	-9999	-0.42	44	44
CSNK1A1	0.022	0.012	-9999	-10000	0	0
GNAS	-0.038	0.14	-9999	-0.4	44	44
GO:0007205	-0.04	0.12	-9999	-0.42	22	22
WNT6	0.009	0.097	-9999	-0.51	17	17
WNT4	-0.042	0.2	-9999	-0.59	57	57
NFAT1/CK1 alpha	-0.017	0.12	-9999	-0.46	12	12
GNG2	0.027	0.008	-9999	-10000	0	0
WNT5A	0.018	0.037	-9999	-0.41	3	3
WNT11	-0.017	0.16	-9999	-0.6	37	37
CDC42	-0.035	0.13	-9999	-0.44	24	24

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

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
BAG4	0.025	0.029	-10000	0	-0.61	1	1
Caspase 8 (4 units)	-0.058	0.1	-10000	0	-0.36	1	1
NEF	-0.054	0.069	-10000	0	-0.41	5	5
NFKBIA	0.012	0.043	-10000	0	-10000	0	0
BIRC3	-0.044	0.18	-10000	0	-0.46	79	79
CYCS	-0.067	0.1	-10000	0	-0.39	1	1
RIPK1	0.028	0.005	-10000	0	-10000	0	0
CD247	-0.22	0.3	-10000	0	-0.63	166	166
MAP2K7	-0.041	0.13	0.38	2	-0.59	15	17
protein ubiquitination	0.027	0.097	0.36	10	-0.49	4	14
CRADD	0.028	0.005	-10000	0	-10000	0	0
DAXX	0.028	0.006	-10000	0	-10000	0	0
FAS	0.028	0.005	-10000	0	-10000	0	0
BID	-0.075	0.11	-10000	0	-0.34	2	2
NF-kappa-B/RelA/I kappa B alpha	0.014	0.11	-10000	0	-0.43	2	2
TRADD	0.028	0.006	-10000	0	-10000	0	0
MAP3K5	0.027	0.008	-10000	0	-10000	0	0
CFLAR	0.028	0.006	-10000	0	-10000	0	0
FADD	0.029	0.003	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.014	0.12	-10000	0	-0.43	2	2
MAPK8	-0.036	0.13	0.43	3	-0.57	13	16
APAF1	0.028	0.005	-10000	0	-10000	0	0
TRAF1	0.027	0.024	-10000	0	-0.5	1	1
TRAF2	0.028	0.005	-10000	0	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.081	0.11	-10000	0	-0.31	6	6
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.009	0.094	-10000	0	-0.52	7	7
CHUK	0.025	0.091	0.3	6	-0.54	4	10
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.075	0.029	-10000	0	-10000	0	0
TCRz/NEF	-0.23	0.27	-10000	0	-0.44	271	271
TNF	0.018	0.073	-10000	0	-0.56	8	8
FASLG	-0.31	0.34	-10000	0	-0.63	255	255
NFKB1	0.011	0.053	-10000	0	-0.6	1	1
TNFR1A/BAG4/TNF-alpha	0.044	0.057	-10000	0	-0.35	9	9
CASP6	-0.022	0.11	-10000	0	-0.55	13	13
CASP7	-0.061	0.14	0.37	1	-0.43	8	9
RELA	0.012	0.045	-10000	0	-10000	0	0
CASP2	0.026	0.009	-10000	0	-10000	0	0
CASP3	-0.058	0.14	0.37	1	-0.44	4	5
TNFRSF1A	0.028	0.006	-10000	0	-10000	0	0
TNFR1A/BAG4	0.037	0.026	-10000	0	-0.45	1	1
CASP8	0.028	0.006	-10000	0	-10000	0	0
CASP9	0.028	0.006	-10000	0	-10000	0	0
MAP3K14	0.017	0.092	-10000	0	-0.57	5	5
APAF-1/Caspase 9	-0.082	0.14	-10000	0	-0.41	47	47
BCL2	-0.03	0.12	0.47	3	-0.54	11	14

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.16	0.19	0.49	1	-0.6	40	41
RAD9A	0.029	0.003	-10000	0	-10000	0	0
AP1	0.026	0.074	-10000	0	-0.44	12	12
IFNAR2	0.027	0.009	-10000	0	-10000	0	0
AKT1	0.013	0.044	-10000	0	-0.3	4	4
ER alpha/Oestrogen	0.016	0.036	-10000	0	-0.37	4	4
NFX1/SIN3/HDAC complex	0.026	0.064	-10000	0	-0.38	5	5
EGF	-0.54	0.19	-10000	0	-0.61	460	460
SMG5	0.027	0.006	-10000	0	-10000	0	0
SMG6	0.028	0.005	-10000	0	-10000	0	0
SP3/HDAC2	0.036	0.017	-10000	0	-10000	0	0
TERT/c-Abl	-0.15	0.18	-10000	0	-0.58	36	36
SAP18	0.028	0.005	-10000	0	-10000	0	0
MRN complex	0.042	0.026	-10000	0	-10000	0	0
WT1	-0.27	0.32	-10000	0	-0.61	235	235
WRN	0.026	0.009	-10000	0	-10000	0	0
SP1	0.025	0.014	-10000	0	-10000	0	0
SP3	0.027	0.006	-10000	0	-10000	0	0
TERF2IP	0.028	0.006	-10000	0	-10000	0	0
Telomerase/Nucleolin	-0.13	0.16	-10000	0	-0.59	17	17
Mad/Max	0.038	0.014	-10000	0	-10000	0	0
TERT	-0.16	0.19	0.49	1	-0.62	39	40
CCND1	-0.15	0.19	0.65	1	-0.65	21	22
MAX	0.026	0.008	-10000	0	-10000	0	0
RBBP7	0.028	0.003	-10000	0	-10000	0	0
RBBP4	0.026	0.029	-10000	0	-0.61	1	1
TERF2	0.025	0.007	-10000	0	-10000	0	0
PTGES3	0.028	0.005	-10000	0	-10000	0	0
SIN3A	0.028	0.003	-10000	0	-10000	0	0
Telomerase/911	0.025	0.042	-10000	0	-10000	0	0
CDKN1B	-0.1	0.15	-10000	0	-0.56	1	1
RAD1	0.026	0.009	-10000	0	-10000	0	0
XRCC5	0.027	0.007	-10000	0	-10000	0	0
XRCC6	0.028	0.004	-10000	0	-10000	0	0
SAP30	0.01	0.096	-10000	0	-0.5	17	17
TRF2/PARP2	0.038	0.012	-10000	0	-10000	0	0
UBE3A	0.028	0.004	-10000	0	-10000	0	0
JUN	0.027	0.006	-10000	0	-10000	0	0
E6	-0.001	0.003	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.019	0.009	-10000	0	-10000	0	0
FOS	0.011	0.096	-10000	0	-0.6	12	12
IFN-gamma/IRF1	-0.12	0.18	-10000	0	-0.35	189	189
PARP2	0.027	0.007	-10000	0	-10000	0	0
BLM	0.018	0.074	-10000	0	-0.5	10	10
Telomerase	-0.019	0.11	-10000	0	-0.6	3	3
IRF1	0.024	0.027	-10000	0	-0.5	1	1
ESR1	0.022	0.049	-10000	0	-0.51	4	4
KU/TER	0.04	0.011	-10000	0	-10000	0	0
ATM/TRF2	0.041	0.022	-10000	0	-0.41	1	1
ubiquitin-dependent protein catabolic process	0.036	0.052	-10000	0	-0.44	1	1
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.037	0.053	-10000	0	-0.45	1	1
HDAC1	0.028	0.006	-10000	0	-10000	0	0
HDAC2	0.024	0.014	-10000	0	-10000	0	0
ATM	0.01	0.021	-10000	0	-0.45	1	1
SMAD3	0.018	0.035	0.22	1	-0.36	4	5
ABL1	0.028	0.005	-10000	0	-10000	0	0
MXD1	0.028	0.006	-10000	0	-10000	0	0
MRE11A	0.028	0.004	-10000	0	-10000	0	0
HUS1	0.026	0.009	-10000	0	-10000	0	0
RPS6KB1	0.028	0.005	-10000	0	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.11	0.18	-10000	0	-0.62	20	20
NR2F2	0.029	0.006	-10000	0	-10000	0	0
MAPK3	0.006	0.054	-10000	0	-0.36	10	10
MAPK1	0.006	0.054	-10000	0	-0.36	10	10
TGFB1/TGF beta receptor Type II	0.025	0.047	-10000	0	-0.5	4	4
NFKB1	0.027	0.029	-10000	0	-0.61	1	1
HNRNPC	0.027	0.007	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.01	0.021	-10000	0	-0.45	1	1
NBN	0.027	0.007	-10000	0	-10000	0	0
EGFR	0.019	0.06	-10000	0	-0.52	6	6
mol:Oestrogen	0	0.002	-10000	0	-10000	0	0
EGF/EGFR	-0.39	0.16	-10000	0	-0.44	446	446
MYC	0.009	0.096	-10000	0	-0.5	17	17
IL2	0.009	0.075	-10000	0	-0.5	10	10
KU	0.04	0.011	-10000	0	-10000	0	0
RAD50	0.022	0.012	-10000	0	-10000	0	0
HSP90AA1	0.027	0.008	-10000	0	-10000	0	0
TGFB1	0.025	0.047	-10000	0	-0.5	4	4
TRF2/BLM	0.032	0.053	-10000	0	-0.34	10	10
FRAP1	0	0	-10000	0	-10000	0	0
KU/TERT	-0.14	0.18	-10000	0	-0.6	29	29
SP1/HDAC2	0.034	0.024	-10000	0	-10000	0	0
PINX1	0.026	0.009	-10000	0	-10000	0	0
Telomerase/EST1A	-0.13	0.17	-10000	0	-0.58	19	19
Smad3/Myc	0.021	0.071	-10000	0	-0.32	20	20
911 complex	0.049	0.022	-10000	0	-10000	0	0
IFNG	-0.21	0.26	-10000	0	-0.49	230	230
Telomerase/PinX1	-0.13	0.16	-10000	0	-0.58	18	18
Telomerase/AKT1/mTOR/p70S6K	-0.02	0.094	-10000	0	-0.42	8	8
SIN3B	0.029	0.003	-10000	0	-10000	0	0
YWHAE	0.028	0.005	-10000	0	-10000	0	0
Telomerase/EST1B	-0.13	0.17	-10000	0	-0.57	21	21
response to DNA damage stimulus	0.005	0.012	-10000	0	-10000	0	0
MRN complex/TRF2/Rap1	0.059	0.038	-10000	0	-10000	0	0
TRF2/WRN	0.036	0.014	-10000	0	-10000	0	0
Telomerase/hnRNP C1/C2	-0.13	0.17	-10000	0	-0.59	16	16
E2F1	-0.028	0.16	-10000	0	-0.51	52	52
ZNFX1	0.028	0.006	-10000	0	-10000	0	0
PIF1	-0.064	0.2	-10000	0	-0.5	89	89
NCL	0.027	0.007	-10000	0	-10000	0	0
DKC1	0.028	0.004	-10000	0	-10000	0	0
telomeric DNA binding	0	0	-10000	0	-10000	0	0

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.064	0.25	-10000	0	-0.88	29	29
NCK1/PAK1/Dok-R	-0.057	0.098	-10000	0	-0.42	26	26
NCK1/Dok-R	0.001	0.27	-10000	0	-1	29	29
PIK3CA	0.025	0.029	-10000	0	-0.61	1	1
mol:beta2-estradiol	-0.002	0.035	0.26	8	-10000	0	8
RELA	0.029	0.003	-10000	0	-10000	0	0
SHC1	0.027	0.006	-10000	0	-10000	0	0
Rac/GDP	0.019	0.007	-10000	0	-10000	0	0
F2	-0.17	0.25	0.27	3	-0.5	186	189
TNIP2	0.028	0.004	-10000	0	-10000	0	0
NF kappa B/RelA	0.037	0.26	-10000	0	-0.96	29	29
FN1	-0.012	0.14	-10000	0	-0.51	37	37
PLD2	-0.005	0.27	-10000	0	-1.1	29	29
PTPN11	0.028	0.005	-10000	0	-10000	0	0
GRB14	-0.006	0.14	-10000	0	-0.61	27	27
ELK1	0.009	0.24	-10000	0	-0.94	29	29
GRB7	0.021	0.069	-10000	0	-0.61	6	6
PAK1	0.029	0.003	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.003	0.28	-10000	0	-1	28	28
CDKN1A	-0.066	0.21	-10000	0	-0.64	21	21
ITGA5	-0.007	0.13	-10000	0	-0.5	34	34
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.003	0.27	-10000	0	-1	29	29
CRK	0.028	0.005	-10000	0	-10000	0	0
mol:NO	-0.025	0.2	0.42	6	-0.64	28	34
PLG	-0.16	0.3	-10000	0	-1.2	29	29
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.043	0.22	-10000	0	-0.83	28	28
GRB2	0.028	0.005	-10000	0	-10000	0	0
PIK3R1	0.024	0.029	-10000	0	-0.61	1	1
ANGPT2	-0.11	0.23	-10000	0	-0.59	27	27
BMX	-0.043	0.28	-10000	0	-1.1	29	29
ANGPT1	0.034	0.17	-10000	0	-1.2	8	8
tube development	-0.083	0.23	-10000	0	-0.71	26	26
ANGPT4	0.005	0.093	-10000	0	-0.51	16	16
response to hypoxia	-0.005	0.015	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.012	0.3	-10000	0	-1.1	29	29
alpha5/beta1 Integrin	0.014	0.1	-10000	0	-0.36	34	34
FGF2	0.027	0.062	-10000	0	-0.59	5	5
STAT5A (dimer)	-0.082	0.26	-10000	0	-0.8	26	26
mol:L-citrulline	-0.025	0.2	0.42	6	-0.64	28	34
AGTR1	-0.023	0.13	-10000	0	-0.6	25	25
MAPK14	-0.032	0.3	-10000	0	-1.1	30	30
Tie2/SHP2	-0.008	0.26	-10000	0	-1.1	27	27
TEK	-0.012	0.29	-10000	0	-1.2	27	27
RPS6KB1	-0.04	0.24	-10000	0	-0.84	29	29
Angiotensin II/AT1	-0.025	0.1	-10000	0	-0.45	25	25
Tie2/Ang1/GRB2	0.007	0.28	-10000	0	-1.1	29	29
MAPK3	0.001	0.25	-10000	0	-0.95	29	29
MAPK1	-0.001	0.25	-10000	0	-0.96	29	29
Tie2/Ang1/GRB7	0.004	0.29	-10000	0	-1.1	29	29
NFKB1	0.027	0.029	-10000	0	-0.61	1	1
MAPK8	-0.006	0.27	-10000	0	-1.1	29	29
PI3K	-0.058	0.28	-10000	0	-1	29	29
FES	-0.027	0.29	-10000	0	-1.1	29	29
Crk/Dok-R	0.004	0.27	-10000	0	-1	28	28
Tie2/Ang1/ABIN2	0.006	0.29	-10000	0	-1.1	29	29
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.054	0.23	0.43	1	-0.78	29	30
STAT5A	0.028	0.004	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.038	0.24	-10000	0	-0.85	28	28
Tie2/Ang2	-0.11	0.29	-10000	0	-0.99	26	26
Tie2/Ang1	-0.008	0.3	-10000	0	-1.2	29	29
FOXO1	-0.07	0.24	0.45	1	-0.8	28	29
ELF1	0.029	0.041	-10000	0	-0.6	1	1
ELF2	-0.006	0.28	-10000	0	-1.1	29	29
mol:Choline	-0.002	0.26	-10000	0	-1	29	29
cell migration	-0.038	0.061	-10000	0	-0.24	23	23
FYN	-0.096	0.25	-10000	0	-0.82	26	26
DOK2	-0.007	0.13	-10000	0	-0.51	31	31
negative regulation of cell cycle	-0.059	0.2	-10000	0	-0.58	21	21
ETS1	0.032	0.04	-10000	0	-0.28	4	4
PXN	-0.021	0.21	0.49	6	-0.69	28	34
ITGB1	0.028	0.004	-10000	0	-10000	0	0
NOS3	-0.033	0.22	0.58	1	-0.73	28	29
RAC1	0.026	0.009	-10000	0	-10000	0	0
TNF	0.019	0.083	-10000	0	-0.45	13	13
MAPKKK cascade	-0.002	0.26	-10000	0	-1	29	29
RASA1	0.024	0.03	-10000	0	-0.61	1	1
Tie2/Ang1/Shc	-0.001	0.28	-10000	0	-1.1	29	29
NCK1	0.026	0.029	-10000	0	-0.61	1	1
vasculogenesis	-0.02	0.19	0.39	10	-0.57	28	38
mol:Phosphatidic acid	-0.002	0.26	-10000	0	-1	29	29
mol:Angiotensin II	-0.009	0.012	-10000	0	-10000	0	0
mol:NADP	-0.025	0.2	0.42	6	-0.64	28	34
Rac1/GTP	-0.039	0.22	-10000	0	-0.78	28	28
MMP2	-0.009	0.27	-10000	0	-1.1	29	29

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	-0.55	0.64	-10000	0	-1.2	237	237
PLK1	-0.12	0.21	-10000	0	-0.71	10	10
CDKN1B	-0.021	0.14	0.52	1	-0.38	1	2
FOXO3	-0.06	0.16	-10000	0	-0.6	10	10
KAT2B	0.012	0.038	-10000	0	-0.65	1	1
FOXO1/SIRT1	-0.14	0.22	-10000	0	-0.38	216	216
CAT	-0.082	0.18	0.47	1	-1.2	3	4
CTNNB1	0.02	0.013	-10000	0	-10000	0	0
AKT1	-0.011	0.05	-10000	0	-0.3	1	1
FOXO1	-0.17	0.23	0.3	1	-0.41	232	233
MAPK10	0.032	0.069	0.34	3	-0.35	4	7
mol:GTP	0.002	0.001	-10000	0	-10000	0	0
FOXO4	0.084	0.085	0.38	13	-10000	0	13
response to oxidative stress	-0.028	0.04	-10000	0	-0.29	1	1
FOXO3A/SIRT1	-0.028	0.18	-10000	0	-0.59	9	9
XPO1	0.029	0.005	-10000	0	-10000	0	0
EP300	-0.012	0.055	-10000	0	-0.47	2	2
BCL2L11	0.003	0.085	-10000	0	-0.74	6	6
FOXO1/SKP2	-0.14	0.21	-10000	0	-0.39	198	198
mol:GDP	-0.028	0.04	-10000	0	-0.29	1	1
RAN	0.029	0.006	-10000	0	-10000	0	0
GADD45A	0.049	0.15	-10000	0	-0.64	13	13
YWHAQ	0.028	0.005	-10000	0	-10000	0	0
FOXO1/14-3-3 family	0.026	0.11	0.27	1	-0.54	9	10
MST1	0.005	0.073	-10000	0	-0.54	8	8
CSNK1D	0.028	0.005	-10000	0	-10000	0	0
CSNK1E	0.028	0.004	-10000	0	-10000	0	0
FOXO4/14-3-3 family	0.024	0.11	-10000	0	-0.62	7	7
YWHAB	0.028	0.006	-10000	0	-10000	0	0
MAPK8	0.034	0.061	0.34	2	-0.35	1	3
MAPK9	0.021	0.048	0.35	2	-10000	0	2
YWHAG	0.026	0.009	-10000	0	-10000	0	0
YWHAE	0.028	0.005	-10000	0	-10000	0	0
YWHAZ	0.027	0.007	-10000	0	-10000	0	0
SIRT1	0.041	0.016	-10000	0	-10000	0	0
SOD2	-0.059	0.18	0.45	1	-0.54	11	12
RBL2	-0.023	0.16	-10000	0	-0.95	6	6
RAL/GDP	0.016	0.034	-10000	0	-10000	0	0
CHUK	0.02	0.025	-10000	0	-10000	0	0
Ran/GTP	0.025	0.005	-10000	0	-10000	0	0
CSNK1G2	0.027	0.029	-10000	0	-0.61	1	1
RAL/GTP	0.023	0.033	-10000	0	-10000	0	0
CSNK1G1	0.029	0.003	-10000	0	-10000	0	0
FASLG	-0.18	0.2	-10000	0	-0.7	8	8
SKP2	0.026	0.009	-10000	0	-10000	0	0
USP7	0.029	0.006	-10000	0	-10000	0	0
IKBKB	0.02	0.024	-10000	0	-10000	0	0
CCNB1	-0.068	0.17	-10000	0	-0.68	7	7
FOXO1-3a-4/beta catenin	-0.043	0.14	0.38	4	-0.41	2	6
proteasomal ubiquitin-dependent protein catabolic process	-0.14	0.21	-10000	0	-0.38	198	198
CSNK1A1	0.022	0.012	-10000	0	-10000	0	0
SGK1	0.019	0.025	-10000	0	-10000	0	0
CSNK1G3	0.022	0.012	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.042	0.011	-10000	0	-10000	0	0
ZFAND5	0.086	0.085	0.45	8	-10000	0	8
SFN	-0.036	0.18	-10000	0	-0.52	59	59
CDK2	-0.021	0.059	-10000	0	-10000	0	0
FOXO3A/14-3-3	0.004	0.11	-10000	0	-0.52	12	12
CREBBP	-0.02	0.058	-10000	0	-10000	0	0
FBXO32	-0.074	0.16	0.47	1	-0.68	4	5
BCL6	-0.029	0.16	-10000	0	-0.74	11	11
RALB	0.029	0.005	-10000	0	-10000	0	0
RALA	0.027	0.009	-10000	0	-10000	0	0
YWHAH	0.028	0.004	-10000	0	-10000	0	0

Visual signal transduction: Rods

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
mol:K +	0.029	0.003	-10000	0	-10000	0	0
GNAT1/GTP	0.006	0.05	-10000	0	-0.41	7	7
Metarhodopsin II/Arrestin	0.017	0.059	-10000	0	-0.31	15	15
PDE6G/GNAT1/GTP	0.015	0.06	-10000	0	-0.36	12	12
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	0.008	0.068	-10000	0	-0.55	7	7
GRK1	0.02	0.005	-10000	0	-10000	0	0
CNG Channel	-0.039	0.14	-10000	0	-0.62	7	7
mol:Na +	-0.04	0.16	-10000	0	-0.51	18	18
mol:ADP	0.02	0.005	-10000	0	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.027	0.11	-10000	0	-0.36	34	34
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	-0.034	0.17	-10000	0	-0.52	18	18
CNGB1	0.014	0.07	-10000	0	-0.5	9	9
RDH5	0.02	0.066	-10000	0	-0.53	7	7
SAG	0.017	0.024	-10000	0	-0.5	1	1
mol:Ca2+	-0.068	0.15	0.38	3	-0.5	17	20
Na + (4 Units)	-0.041	0.15	-10000	0	-0.48	17	17
RGS9	0.013	0.091	-10000	0	-0.52	14	14
GNB1/GNGT1	-0.082	0.18	-10000	0	-0.36	150	150
GNAT1/GDP	0.015	0.1	-10000	0	-0.34	29	29
GUCY2D	0	0.11	-10000	0	-0.5	25	25
GNGT1	-0.13	0.24	-10000	0	-0.5	150	150
GUCY2F	0.019	0.004	-10000	0	-10000	0	0
GNB5	0.029	0.003	-10000	0	-10000	0	0
mol:GMP (4 units)	0.003	0.082	-10000	0	-0.43	10	10
mol:11-cis-retinal	0.02	0.066	-10000	0	-0.53	7	7
mol:cGMP	0.019	0.091	-10000	0	-0.43	4	4
GNB1	0.028	0.006	-10000	0	-10000	0	0
Rhodopsin	0.019	0.084	-10000	0	-0.37	22	22
SLC24A1	0.029	0.003	-10000	0	-10000	0	0
CNGA1	-0.086	0.24	-10000	0	-0.6	93	93
Metarhodopsin II	0.017	0.053	-10000	0	-0.28	15	15
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.028	0.098	-10000	0	-0.45	4	4
RGS9BP	-0.001	0.13	-10000	0	-0.61	23	23
Metarhodopsin II/Transducin	-0.051	0.11	-10000	0	-0.32	48	48
GCAP Family/Ca ++	0.031	0.062	-10000	0	-0.31	15	15
PDE6A/B	0.016	0.082	-10000	0	-0.41	17	17
mol:Pi	0.026	0.11	-10000	0	-0.36	34	34
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	-0.064	0.15	-10000	0	-0.28	152	152
PDE6B	0.022	0.063	-10000	0	-0.61	5	5
PDE6A	0.007	0.084	-10000	0	-0.5	13	13
PDE6G	0.022	0.061	-10000	0	-0.59	5	5
RHO	0.008	0.089	-10000	0	-0.5	15	15
PDE6	0.026	0.12	-10000	0	-0.6	5	5
GUCA1A	0.012	0.07	-10000	0	-0.5	9	9
GC2/GCAP Family	0.041	0.066	-10000	0	-0.43	3	3
GUCA1C	0.016	0.04	-10000	0	-0.61	2	2
GUCA1B	0.022	0.053	-10000	0	-0.5	5	5

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

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
MAP4K1	-0.09	0.16	-10000	0	-0.58	20	20
CRKL	0.005	0.11	-10000	0	-0.47	20	20
HRAS	-0.009	0.13	-10000	0	-0.51	10	10
mol:PIP3	0.011	0.11	0.27	1	-0.45	19	20
SPRED1	0.029	0.003	-10000	0	-10000	0	0
SPRED2	0.027	0.029	-10000	0	-0.61	1	1
GAB1	0.004	0.12	-10000	0	-0.5	21	21
FOXO3	0.01	0.14	0.34	3	-0.53	18	21
AKT1	0.008	0.16	0.3	4	-0.52	25	29
BAD	0.011	0.15	0.33	4	-0.53	18	22
megakaryocyte differentiation	-0.051	0.17	-10000	0	-0.43	54	54
GSK3B	0.012	0.15	0.31	7	-0.52	19	26
RAF1	-0.016	0.1	0.3	2	-0.41	9	11
SHC1	0.027	0.006	-10000	0	-10000	0	0
STAT3	0.003	0.12	-10000	0	-0.5	21	21
STAT1	-0.012	0.24	-10000	0	-1.1	21	21
HRAS/SPRED1	0.006	0.11	-10000	0	-0.41	9	9
cell proliferation	0.002	0.12	-10000	0	-0.51	21	21
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
TEC	0.028	0.004	-10000	0	-10000	0	0
RPS6KB1	0.009	0.13	-10000	0	-0.51	23	23
HRAS/SPRED2	0.004	0.11	-10000	0	-0.42	9	9
LYN/TEC/p62DOK	0.041	0.12	-10000	0	-0.46	20	20
MAPK3	0.011	0.092	0.29	10	-0.31	5	15
STAP1	-0.23	0.18	-10000	0	-0.38	154	154
GRAP2	-0.008	0.14	-10000	0	-0.51	35	35
JAK2	-0.012	0.22	-10000	0	-1	21	21
STAT1 (dimer)	-0.009	0.23	-10000	0	-1.1	21	21
mol:Gleevec	-0.002	0.005	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.027	0.16	-10000	0	-0.53	20	20
actin filament polymerization	-0.001	0.11	-10000	0	-0.49	20	20
LYN	0.027	0.007	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.2	0.2	-10000	0	-0.72	30	30
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
CBL/CRKL/GRB2	0.034	0.11	-10000	0	-0.45	15	15
PI3K	0.03	0.13	-10000	0	-0.5	18	18
PTEN	0.027	0.006	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.045	0.27	-10000	0	-1.2	21	21
MAPK8	0.002	0.12	-10000	0	-0.52	21	21
STAT3 (dimer)	0.003	0.12	-10000	0	-0.49	21	21
positive regulation of transcription	0.014	0.082	0.27	12	-0.27	3	15
mol:GDP	-0.023	0.15	-10000	0	-0.58	9	9
PIK3C2B	0.003	0.12	-10000	0	-0.49	21	21
CBL/CRKL	0.021	0.11	-10000	0	-0.45	18	18
FER	-0.002	0.12	-10000	0	-0.5	20	20
SH2B3	0.004	0.12	-10000	0	-0.5	21	21
PDPK1	0.02	0.11	0.34	6	-0.42	17	23
SNAI2	0.002	0.12	-10000	0	-0.51	21	21
positive regulation of cell proliferation	0.009	0.18	-10000	0	-0.8	21	21
KITLG	0.017	0.092	-10000	0	-0.63	10	10
cell motility	0.009	0.18	-10000	0	-0.8	21	21
PTPN6	0.026	0.008	-10000	0	-10000	0	0
EPOR	0.039	0.094	-10000	0	-1.1	2	2
STAT5A (dimer)	0.021	0.16	-10000	0	-0.65	22	22
SOCS1	0.021	0.058	-10000	0	-0.5	6	6
cell migration	0.022	0.14	0.51	26	-10000	0	26
SOS1	0.028	0.005	-10000	0	-10000	0	0
EPO	-0.14	0.24	-10000	0	-0.5	163	163
VAV1	-0.099	0.23	-10000	0	-0.5	122	122
GRB10	0	0.11	0.24	1	-0.5	20	21
PTPN11	0.027	0.007	-10000	0	-10000	0	0
SCF/KIT	0.004	0.12	-10000	0	-0.52	22	22
GO:0007205	-0.001	0.006	-10000	0	-10000	0	0
MAP2K1	-0.01	0.086	0.3	3	-0.35	5	8
CBL	0.027	0.028	-10000	0	-0.61	1	1
KIT	-0.007	0.27	-10000	0	-1.3	21	21
MAP2K2	-0.01	0.086	0.35	3	-0.35	5	8
SHC/Grb2/SOS1	0.042	0.12	-10000	0	-0.48	15	15
STAT5A	0.02	0.17	-10000	0	-0.68	22	22
GRB2	0.028	0.005	-10000	0	-10000	0	0
response to radiation	0.003	0.12	0.28	1	-0.49	21	22
SHC/GRAP2	0.013	0.1	-10000	0	-0.36	34	34
PTPRO	-0.052	0.18	-10000	0	-0.44	54	54
SH2B2	-0.001	0.12	-10000	0	-0.5	20	20
DOK1	0.028	0.005	-10000	0	-10000	0	0
MATK	-0.023	0.15	-10000	0	-0.53	26	26
CREBBP	0.043	0.03	-10000	0	-10000	0	0
BCL2	0.038	0.094	-10000	0	-0.86	2	2

Thromboxane A2 receptor signaling

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
TGM2	0.022	0.058	-10000	0	-0.5	6	6
GNB1/GNG2	-0.025	0.051	-10000	0	-0.18	33	33
AKT1	0.021	0.11	0.3	6	-0.3	23	29
EGF	-0.54	0.19	-10000	0	-0.61	460	460
mol:TXA2	0	0	-10000	0	-10000	0	0
FGR	0.011	0.067	0.33	3	-0.33	2	5
mol:Ca2+	0.034	0.12	0.32	6	-0.3	32	38
LYN	0.01	0.061	0.37	2	-10000	0	2
RhoA/GTP	0.007	0.044	-10000	0	-10000	0	0
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	0.03	0.12	0.35	5	-0.34	33	38
GNG2	0.027	0.008	-10000	0	-10000	0	0
ARRB2	0.027	0.029	-10000	0	-0.62	1	1
TP alpha/Gq family/GDP/G beta5/gamma2	0.013	0.075	0.31	2	-0.48	5	7
G beta5/gamma2	-0.032	0.068	-10000	0	-0.24	33	33
PRKCH	0.027	0.12	0.37	3	-0.34	32	35
DNM1	0.018	0.072	-10000	0	-0.52	9	9
TXA2/TP beta/beta Arrestin3	0.005	0.031	-10000	0	-0.42	1	1
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
PTGDR	-0.052	0.19	-10000	0	-0.5	75	75
G12 family/GTP	0.007	0.095	-10000	0	-0.3	27	27
ADRBK1	0.029	0.003	-10000	0	-10000	0	0
ADRBK2	0.028	0.004	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0.028	0.018	-10000	0	-10000	0	0
mol:GDP	-0.028	0.086	0.42	4	-0.32	3	7
mol:NADP	0.026	0.009	-10000	0	-10000	0	0
RAB11A	0.029	0.003	-10000	0	-10000	0	0
PRKG1	0.013	0.097	-10000	0	-0.61	12	12
mol:IP3	0.032	0.14	0.38	4	-0.37	32	36
cell morphogenesis	0.027	0.018	-10000	0	-10000	0	0
PLCB2	0.026	0.17	0.45	3	-0.5	33	36
mol:cGMP	0	0	-10000	0	-10000	0	0
BLK	-0.005	0.088	0.37	2	-0.33	15	17
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.002	0.081	0.38	1	-0.32	9	10
RHOA	0.021	0.013	-10000	0	-10000	0	0
PTGIR	0.026	0.037	-10000	0	-0.56	2	2
PRKCB1	0.029	0.13	0.36	4	-0.37	35	39
GNAQ	0.028	0.006	-10000	0	-10000	0	0
mol:L-citrulline	0.026	0.009	-10000	0	-10000	0	0
TXA2/TXA2-R family	0.025	0.18	0.45	3	-0.51	35	38
LCK	0.003	0.084	0.33	3	-0.33	12	15
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.008	0.069	-10000	0	-10000	0	0
TXA2-R family/G12 family/GDP/G beta/gamma	0.012	0.083	-10000	0	-0.42	15	15
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.011	0.07	-10000	0	-0.3	1	1
MAPK14	0.03	0.092	0.27	10	-0.24	16	26
TGM2/GTP	0.031	0.15	0.38	2	-0.41	30	32
MAPK11	0.032	0.092	0.27	10	-0.25	15	25
ARHGEF1	0.017	0.064	-10000	0	-0.19	10	10
GNAI2	0.02	0.013	-10000	0	-10000	0	0
JNK cascade	0.031	0.14	0.37	5	-0.38	35	40
RAB11/GDP	0.028	0.003	-10000	0	-10000	0	0
ICAM1	0.031	0.11	0.32	5	-0.29	37	42
cAMP biosynthetic process	0.028	0.13	0.36	5	-0.35	31	36
Gq family/GTP/EBP50	0.015	0.05	0.23	3	-0.24	4	7
actin cytoskeleton reorganization	0.027	0.018	-10000	0	-10000	0	0
SRC	0.01	0.058	0.38	1	-10000	0	1
GNB5	0.029	0.003	-10000	0	-10000	0	0
GNB1	0.028	0.006	-10000	0	-10000	0	0
EGF/EGFR	-0.1	0.08	0.27	2	-0.3	15	17
VCAM1	0.029	0.12	0.29	7	-0.3	36	43
TP beta/Gq family/GDP/G beta5/gamma2	0.013	0.075	0.31	2	-0.48	5	7
platelet activation	0.04	0.12	0.34	11	-0.3	30	41
PGI2/IP	0.02	0.027	-10000	0	-0.41	2	2
PRKACA	-0.005	0.07	-10000	0	-0.29	2	2
Gq family/GDP/G beta5/gamma2	0.01	0.072	0.26	1	-0.44	5	6
TXA2/TP beta/beta Arrestin2	0.002	0.044	-10000	0	-0.35	4	4
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.006	0.065	-10000	0	-0.28	2	2
mol:DAG	0.031	0.15	0.39	4	-0.41	35	39
EGFR	0.019	0.06	-10000	0	-0.52	6	6
TXA2/TP alpha	0.029	0.17	0.47	3	-0.47	32	35
Gq family/GTP	0.011	0.046	-10000	0	-0.27	9	9
YES1	0.012	0.063	0.37	2	-10000	0	2
GNAI2/GTP	0.001	0.058	-10000	0	-10000	0	0
PGD2/DP	-0.037	0.14	-10000	0	-0.36	75	75
SLC9A3R1	0.028	0.005	-10000	0	-10000	0	0
FYN	0.011	0.062	0.33	3	-10000	0	3
mol:NO	0.026	0.009	-10000	0	-10000	0	0
GNA15	0.013	0.09	-10000	0	-0.5	15	15
PGK/cGMP	0.025	0.062	-10000	0	-0.39	10	10
RhoA/GDP	0.02	0.013	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0.025	0.08	-10000	0	-0.37	1	1
NOS3	0.026	0.009	-10000	0	-10000	0	0
RAC1	0.026	0.009	-10000	0	-10000	0	0
PRKCA	0.032	0.13	0.36	6	-0.35	30	36
PRKCB	0.033	0.13	0.34	12	-0.36	34	46
PRKCE	0.032	0.13	0.34	5	-0.35	32	37
PRKCD	0.009	0.13	0.41	3	-0.37	36	39
PRKCG	0.025	0.14	0.42	3	-0.39	38	41
muscle contraction	0.028	0.16	0.42	4	-0.48	35	39
PRKCZ	0.029	0.12	0.33	6	-0.34	34	40
ARR3	0.021	0.005	-10000	0	-10000	0	0
TXA2/TP beta	0.018	0.071	-10000	0	-10000	0	0
PRKCQ	0.025	0.13	0.36	5	-0.37	33	38
MAPKKK cascade	0.026	0.16	0.43	3	-0.44	34	37
SELE	0.023	0.14	0.29	7	-0.4	37	44
TP beta/GNAI2/GDP/G beta/gamma	0.016	0.072	-10000	0	-10000	0	0
ROCK1	0.028	0.004	-10000	0	-10000	0	0
GNA14	0.02	0.069	-10000	0	-0.61	6	6
chemotaxis	0.022	0.2	0.46	3	-0.59	37	40
GNA12	0.026	0.009	-10000	0	-10000	0	0
GNA13	0.028	0.005	-10000	0	-10000	0	0
GNA11	0.025	0.049	-10000	0	-0.61	3	3
Rac1/GTP	0.019	0.007	-10000	0	-10000	0	0

Syndecan-2-mediated signaling events

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
Syndecan-2/Fibronectin	0.009	0.084	-10000	0	-0.3	33	33
EPHB2	0.019	0.07	-10000	0	-0.48	9	9
Syndecan-2/TACI	-0.001	0.098	-10000	0	-0.3	49	49
LAMA1	0.013	0.095	-10000	0	-0.54	14	14
Syndecan-2/alpha2 ITGB1	0.051	0.05	-10000	0	-0.33	3	3
HRAS	0.028	0.024	-10000	0	-0.5	1	1
Syndecan-2/CASK	0.013	0.003	-10000	0	-10000	0	0
ITGA5	-0.007	0.13	-10000	0	-0.5	34	34
BAX	0.018	0.017	-10000	0	-10000	0	0
EPB41	0.028	0.006	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	0.03	0.008	-10000	0	-10000	0	0
LAMA3	0.022	0.058	-10000	0	-0.5	6	6
EZR	0.026	0.008	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	0.021	0.053	-10000	0	-0.5	5	5
Syndecan-2/MMP2	0.029	0.033	-10000	0	-0.32	4	4
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.034	0.046	-10000	0	-0.45	4	4
dendrite morphogenesis	0.027	0.041	-10000	0	-0.38	4	4
Syndecan-2/GM-CSF	0.014	0.053	-10000	0	-0.3	13	13
determination of left/right symmetry	0.018	0.004	-10000	0	-10000	0	0
Syndecan-2/PKC delta	0.024	0.022	-10000	0	-0.3	1	1
GNB2L1	0.022	0.012	-10000	0	-10000	0	0
MAPK3	0.011	0.052	-10000	0	-0.27	13	13
MAPK1	0.012	0.053	-10000	0	-0.27	13	13
Syndecan-2/RACK1	0.035	0.026	-10000	0	-0.26	1	1
NF1	0.028	0.004	-10000	0	-10000	0	0
FGFR/FGF/Syndecan-2	0.018	0.004	-10000	0	-10000	0	0
ITGA2	0.021	0.059	-10000	0	-0.55	5	5
MAPK8	0.02	0.019	-10000	0	-0.38	1	1
Syndecan-2/alpha2/beta1 Integrin	0.047	0.066	-10000	0	-0.32	12	12
Syndecan-2/Kininogen	-0.26	0.18	-10000	0	-0.38	351	351
ITGB1	0.028	0.004	-10000	0	-10000	0	0
SRC	0.061	0.067	0.35	1	-10000	0	1
Syndecan-2/CASK/Protein 4.1	0.029	0.009	-10000	0	-10000	0	0
extracellular matrix organization	0.03	0.031	-10000	0	-0.3	4	4
actin cytoskeleton reorganization	0.009	0.084	-10000	0	-0.3	33	33
Syndecan-2/Caveolin-2/Ras	0.041	0.037	-10000	0	-0.27	5	5
Syndecan-2/Laminin alpha3	0.029	0.035	-10000	0	-0.3	5	5
Syndecan-2/RasGAP	0.044	0.039	-10000	0	-0.56	1	1
alpha5/beta1 Integrin	0.014	0.1	-10000	0	-0.36	34	34
PRKCD	0.02	0.027	-10000	0	-0.5	1	1
Syndecan-2 dimer	0.028	0.041	-10000	0	-0.38	4	4
GO:0007205	0.003	0	-10000	0	-10000	0	0
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	0.057	0.057	-10000	0	-0.54	1	1
RHOA	0.021	0.013	-10000	0	-10000	0	0
SDCBP	0.027	0.007	-10000	0	-10000	0	0
TNFRSF13B	-0.025	0.16	-10000	0	-0.5	50	50
RASA1	0.024	0.03	-10000	0	-0.61	1	1
alpha2/beta1 Integrin	0.034	0.046	-10000	0	-0.45	4	4
Syndecan-2/Synbindin	0.033	0.009	-10000	0	-10000	0	0
TGFB1	0.024	0.047	-10000	0	-0.5	4	4
CASP3	0.022	0.033	-10000	0	-0.27	1	1
FN1	-0.012	0.14	-10000	0	-0.51	37	37
Syndecan-2/IL8	0.01	0.087	-10000	0	-0.32	32	32
SDC2	0.018	0.004	-10000	0	-10000	0	0
KNG1	-0.43	0.28	-10000	0	-0.6	370	370
Syndecan-2/Neurofibromin	0.033	0.009	-10000	0	-10000	0	0
TRAPPC4	0.029	0.003	-10000	0	-10000	0	0
CSF2	0.003	0.086	-10000	0	-0.5	14	14
Syndecan-2/TGFB1	0.03	0.031	-10000	0	-0.3	4	4
Syndecan-2/Syntenin/PI-4-5-P2	0.03	0.008	-10000	0	-10000	0	0
Syndecan-2/Ezrin	0.034	0.025	-10000	0	-10000	0	0
PRKACA	0.03	0.031	-10000	0	-10000	0	0
angiogenesis	0.01	0.087	-10000	0	-0.32	32	32
MMP2	0.022	0.055	-10000	0	-0.52	5	5
IL8	-0.009	0.14	-10000	0	-0.53	34	34
calcineurin-NFAT signaling pathway	-0.001	0.098	-10000	0	-0.3	49	49

EPO signaling pathway

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
BCL2L1	0.026	0.096	0.45	3	-10000	0	3
CRKL	-0.019	0.14	0.37	15	-10000	0	15
mol:DAG	-0.014	0.099	-10000	0	-10000	0	0
HRAS	-0.001	0.14	0.39	20	-10000	0	20
MAPK8	-0.045	0.15	0.31	2	-0.36	1	3
RAP1A	-0.02	0.14	0.37	16	-10000	0	16
GAB1	-0.021	0.14	0.36	14	-10000	0	14
MAPK14	-0.044	0.15	0.31	2	-10000	0	2
EPO	-0.14	0.24	-10000	0	-0.5	163	163
PLCG1	-0.015	0.1	-10000	0	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0.016	0.03	-10000	0	-10000	0	0
RAPGEF1	0.028	0.005	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.057	0.16	-10000	0	-0.29	161	161
GAB1/SHC/GRB2/SOS1	-0.004	0.13	-10000	0	-10000	0	0
EPO/EPOR (dimer)	-0.086	0.19	-10000	0	-0.36	163	163
IRS2	-0.024	0.14	0.36	14	-0.45	1	15
STAT1	-0.008	0.1	-10000	0	-10000	0	0
STAT5B	-0.011	0.1	-10000	0	-10000	0	0
cell proliferation	-0.04	0.14	0.36	7	-0.33	1	8
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.024	0.1	-10000	0	-0.39	1	1
TEC	-0.021	0.14	0.36	14	-10000	0	14
SOCS3	0.026	0.034	-10000	0	-0.5	2	2
STAT1 (dimer)	-0.006	0.1	-10000	0	-10000	0	0
JAK2	0.014	0.03	-10000	0	-10000	0	0
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
EPO/EPOR (dimer)/JAK2	-0.013	0.14	-10000	0	-10000	0	0
EPO/EPOR	-0.086	0.19	-10000	0	-0.36	163	163
LYN	0.029	0.008	-10000	0	-10000	0	0
TEC/VAV2	-0.015	0.13	0.29	5	-10000	0	5
elevation of cytosolic calcium ion concentration	0.016	0.03	-10000	0	-10000	0	0
SHC1	0.027	0.006	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	-0.051	0.16	-10000	0	-0.28	153	153
mol:IP3	-0.014	0.099	-10000	0	-10000	0	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.012	0.13	0.34	6	-0.42	2	8
SH2B3	0.013	0.028	-10000	0	-10000	0	0
NFKB1	-0.044	0.15	0.31	2	-0.59	1	3
EPO/EPOR (dimer)/JAK2/SOCS3	-0.036	0.083	-10000	0	-0.31	4	4
PTPN6	-0.031	0.13	0.3	3	-10000	0	3
TEC/VAV2/GRB2	-0.007	0.13	0.29	4	-10000	0	4
EPOR	0.016	0.03	-10000	0	-10000	0	0
INPP5D	0.023	0.047	-10000	0	-0.5	4	4
mol:GDP	-0.005	0.13	-10000	0	-10000	0	0
SOS1	0.028	0.005	-10000	0	-10000	0	0
PLCG2	0.02	0.068	-10000	0	-0.55	7	7
CRKL/CBL/C3G	-0.006	0.13	0.29	5	-0.48	1	6
VAV2	-0.02	0.14	0.37	14	-10000	0	14
CBL	-0.022	0.14	0.35	13	-0.52	1	14
SHC/Grb2/SOS1	-0.03	0.11	-10000	0	-10000	0	0
STAT5A	-0.011	0.1	-10000	0	-10000	0	0
GRB2	0.028	0.005	-10000	0	-10000	0	0
STAT5 (dimer)	0.004	0.11	-10000	0	-10000	0	0
LYN/PLCgamma2	0.035	0.05	-10000	0	-0.39	6	6
PTPN11	0.028	0.005	-10000	0	-10000	0	0
BTK	-0.074	0.18	0.37	14	-0.45	28	42
BCL2	0.028	0.099	0.42	4	-10000	0	4

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.028	0.004	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	0.022	0.051	-10000	0	-0.32	3	3
NT3 (dimer)/TRKC	0.012	0.12	-10000	0	-0.47	26	26
NT3 (dimer)/TRKB	-0.044	0.19	-10000	0	-0.38	105	105
SHC/Grb2/SOS1/GAB1/PI3K	0.033	0.03	-10000	0	-0.44	1	1
RAPGEF1	0.028	0.005	-10000	0	-10000	0	0
BDNF	-0.042	0.18	-10000	0	-0.51	67	67
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
DYNLT1	0.026	0.008	-10000	0	-10000	0	0
NTRK1	-0.016	0.16	-10000	0	-0.58	36	36
NTRK2	-0.087	0.24	-10000	0	-0.59	95	95
NTRK3	-0.007	0.15	-10000	0	-0.61	28	28
NT-4/5 (dimer)/TRKB	-0.052	0.19	-10000	0	-0.39	111	111
neuron apoptosis	0.074	0.18	0.5	41	-10000	0	41
SHC 2-3/Grb2	-0.081	0.19	-10000	0	-0.55	41	41
SHC1	0.027	0.006	-10000	0	-10000	0	0
SHC2	-0.04	0.13	-10000	0	-0.5	21	21
SHC3	-0.11	0.22	-10000	0	-0.56	85	85
STAT3 (dimer)	0.026	0.048	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	-0.004	0.14	-10000	0	-0.36	68	68
RIN/GDP	0.044	0.084	0.29	15	-0.3	6	21
GIPC1	0.027	0.028	-10000	0	-0.61	1	1
KRAS	0.028	0.005	-10000	0	-10000	0	0
DNAJA3	-0.027	0.097	-10000	0	-0.38	16	16
RIN/GTP	0.014	0.017	-10000	0	-0.36	1	1
CCND1	0.011	0.084	-10000	0	-0.43	18	18
MAGED1	0.029	0.003	-10000	0	-10000	0	0
PTPN11	0.028	0.005	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.017	0.049	-10000	0	-0.53	4	4
SHC/GRB2/SOS1	0.054	0.016	-10000	0	-10000	0	0
GRB2	0.028	0.005	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.043	0.18	-10000	0	-0.35	120	120
TRKA/NEDD4-2	0.006	0.12	-10000	0	-0.44	33	33
ELMO1	0.025	0.025	-10000	0	-0.5	1	1
RhoG/GTP/ELMO1/DOCK1	0.032	0.027	-10000	0	-0.35	2	2
NGF	-0.021	0.15	-10000	0	-0.5	47	47
HRAS	0.028	0.024	-10000	0	-0.5	1	1
DOCK1	0.026	0.029	-10000	0	-0.61	1	1
GAB2	0.029	0.003	-10000	0	-10000	0	0
RIT2	0.019	0.024	-10000	0	-0.5	1	1
RIT1	0.027	0.006	-10000	0	-10000	0	0
FRS2	0.028	0.005	-10000	0	-10000	0	0
DNM1	0.018	0.072	-10000	0	-0.52	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.028	0.005	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.011	0.1	-10000	0	-0.37	15	15
mol:GDP	0.05	0.12	0.4	15	-0.44	9	24
NGF (dimer)	-0.021	0.15	-10000	0	-0.5	47	47
RhoG/GDP	0.018	0.018	-10000	0	-0.36	1	1
RIT1/GDP	0.045	0.078	0.3	12	-0.3	5	17
TIAM1	0.028	0.006	-10000	0	-10000	0	0
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
BDNF (dimer)/TRKB	-0.068	0.2	-10000	0	-0.38	142	142
KIDINS220/CRKL/C3G	0.041	0.009	-10000	0	-10000	0	0
SHC/RasGAP	0.035	0.027	-10000	0	-0.45	1	1
FRS2 family/SHP2	0.054	0.016	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0.068	0.022	-10000	0	-10000	0	0
RIT1/GTP	0.02	0.005	-10000	0	-10000	0	0
NT3 (dimer)	0.022	0.059	-10000	0	-0.57	5	5
RAP1/GDP	0.03	0.055	-10000	0	-0.26	4	4
KIDINS220/CRKL	0.028	0.004	-10000	0	-10000	0	0
BDNF (dimer)	-0.042	0.18	-10000	0	-0.51	67	67
ubiquitin-dependent protein catabolic process	-0.009	0.14	-10000	0	-0.34	78	78
Schwann cell development	-0.018	0.025	-10000	0	-10000	0	0
EHD4	0.029	0.003	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.067	0.022	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.037	0.024	-10000	0	-10000	0	0
RAP1B	0.028	0.005	-10000	0	-10000	0	0
RAP1A	0.028	0.005	-10000	0	-10000	0	0
CDC42/GTP	-0.057	0.18	-10000	0	-0.57	25	25
ABL1	0.028	0.005	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.041	0.009	-10000	0	-10000	0	0
Rap1/GTP	-0.002	0.1	-10000	0	-0.46	8	8
STAT3	0.026	0.048	-10000	0	-10000	0	0
axon guidance	-0.064	0.17	-10000	0	-0.55	25	25
MAPK3	-0.054	0.15	-10000	0	-0.41	37	37
MAPK1	-0.053	0.15	-10000	0	-0.41	37	37
CDC42/GDP	0.052	0.086	0.33	16	-0.31	4	20
NTF3	0.022	0.059	-10000	0	-0.57	5	5
NTF4	0.017	0.049	-10000	0	-0.53	4	4
NGF (dimer)/TRKA/FAIM	-0.01	0.14	-10000	0	-0.39	32	32
PI3K	0.036	0.034	-10000	0	-0.45	2	2
FRS3	0.028	0.006	-10000	0	-10000	0	0
FAIM	0.027	0.007	-10000	0	-10000	0	0
GAB1	0.028	0.004	-10000	0	-10000	0	0
RASGRF1	-0.031	0.1	-10000	0	-0.38	20	20
SOS1	0.028	0.005	-10000	0	-10000	0	0
MCF2L	0.001	0.098	-10000	0	-0.4	26	26
RGS19	0.028	0.005	-10000	0	-10000	0	0
CDC42	0.028	0.006	-10000	0	-10000	0	0
RAS family/GTP	0.046	0.093	0.31	6	-0.57	6	12
Rac1/GDP	0.041	0.073	0.28	7	-0.31	5	12
NGF (dimer)/TRKA/GRIT	-0.024	0.14	-10000	0	-0.34	79	79
neuron projection morphogenesis	0.003	0.15	0.38	2	-0.97	7	9
NGF (dimer)/TRKA/NEDD4-2	-0.009	0.14	-10000	0	-0.34	78	78
MAP2K1	0.037	0.048	0.43	3	-10000	0	3
NGFR	-0.008	0.14	-10000	0	-0.51	34	34
NGF (dimer)/TRKA/GIPC/GAIP	-0.005	0.097	-10000	0	-0.39	11	11
RAS family/GTP/PI3K	0.027	0.031	-10000	0	-0.42	2	2
FRS2 family/SHP2/GRB2/SOS1	0.077	0.027	-10000	0	-10000	0	0
NRAS	0.028	0.005	-10000	0	-10000	0	0
GRB2/SOS1	0.041	0.009	-10000	0	-10000	0	0
PRKCI	0.027	0.007	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.026	0.009	-10000	0	-10000	0	0
PRKCZ	0.024	0.049	-10000	0	-0.61	3	3
MAPKKK cascade	-0.061	0.2	-10000	0	-0.61	51	51
RASA1	0.024	0.03	-10000	0	-0.61	1	1
TRKA/c-Abl	0.006	0.12	-10000	0	-0.44	33	33
SQSTM1	0.021	0.013	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.051	0.19	-10000	0	-0.38	90	90
NGF (dimer)/TRKA/p62/Atypical PKCs	0.012	0.12	-10000	0	-0.34	18	18
MATK	-0.026	0.16	-10000	0	-0.51	52	52
NEDD4L	0.027	0.029	-10000	0	-0.61	1	1
RAS family/GDP	-0.009	0.035	-10000	0	-0.26	1	1
NGF (dimer)/TRKA	-0.027	0.1	-10000	0	-0.32	39	39
Rac1/GTP	-0.013	0.07	-10000	0	-0.32	6	6
FRS2 family/SHP2/CRK family	0.078	0.026	-10000	0	-10000	0	0

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	-0.002	0.22	-10000	0	-1.1	20	20
MKNK1	0.028	0.006	-10000	0	-10000	0	0
MAPK14	0.028	0.073	-10000	0	-0.3	20	20
ATF2/c-Jun	0.024	0.059	-10000	0	-0.38	1	1
MAPK11	0.028	0.079	-10000	0	-0.31	22	22
MITF	0.017	0.09	-10000	0	-0.38	21	21
MAPKAPK5	0.027	0.083	-10000	0	-0.35	20	20
KRT8	0.027	0.085	-10000	0	-0.35	21	21
MAPKAPK3	0.021	0.013	-10000	0	-10000	0	0
MAPKAPK2	0.028	0.006	-10000	0	-10000	0	0
p38alpha-beta/CK2	0.036	0.11	-10000	0	-0.46	21	21
CEBPB	0.025	0.088	-10000	0	-0.35	20	20
SLC9A1	0.026	0.088	-10000	0	-0.36	21	21
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	0.03	0.087	-10000	0	-0.34	22	22
p38alpha-beta/MNK1	0.05	0.096	-10000	0	-0.37	20	20
JUN	0.026	0.06	-10000	0	-0.38	1	1
PPARGC1A	-0.008	0.14	-10000	0	-0.35	66	66
USF1	0.027	0.08	-10000	0	-0.34	20	20
RAB5/GDP/GDI1	0.019	0.063	-10000	0	-0.39	2	2
NOS2	0.028	0.09	-10000	0	-0.5	2	2
DDIT3	0.026	0.088	-10000	0	-0.36	22	22
RAB5A	0.021	0.013	-10000	0	-10000	0	0
HSPB1	0.04	0.1	0.3	41	-0.42	4	45
p38alpha-beta/HBP1	0.045	0.093	-10000	0	-0.37	18	18
CREB1	0.027	0.092	-10000	0	-0.39	20	20
RAB5/GDP	0.015	0.01	-10000	0	-10000	0	0
EIF4E	0.024	0.077	-10000	0	-0.5	2	2
RPS6KA4	0.028	0.085	-10000	0	-0.36	20	20
PLA2G4A	0.018	0.087	-10000	0	-0.45	6	6
GDI1	0.028	0.085	-10000	0	-0.35	21	21
TP53	0.017	0.1	-10000	0	-0.45	21	21
RPS6KA5	0.025	0.09	-10000	0	-0.38	20	20
ESR1	0.023	0.093	-10000	0	-0.37	23	23
HBP1	0.026	0.009	-10000	0	-10000	0	0
MEF2C	0.025	0.08	-10000	0	-0.36	17	17
MEF2A	0.029	0.083	-10000	0	-0.36	19	19
EIF4EBP1	0.022	0.099	-10000	0	-0.41	20	20
KRT19	-0.041	0.18	-10000	0	-0.37	97	97
ELK4	0.027	0.082	-10000	0	-0.35	20	20
ATF6	0.027	0.08	-10000	0	-0.34	20	20
ATF1	0.027	0.092	-10000	0	-0.39	20	20
p38alpha-beta/MAPKAPK2	0.05	0.094	-10000	0	-0.36	21	21
p38alpha-beta/MAPKAPK3	0.034	0.095	-10000	0	-0.58	2	2

Endothelins

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
AKT1	0.002	0.15	0.37	2	-0.45	5	7
PTK2B	0.026	0.009	-10000	0	-10000	0	0
mol:Ca2+	0.041	0.14	0.47	2	-0.67	6	8
EDN1	0.003	0.14	0.45	1	-0.44	21	22
EDN3	0.012	0.077	-10000	0	-0.5	11	11
EDN2	-0.04	0.18	-10000	0	-0.51	64	64
HRAS/GDP	0.029	0.14	0.31	5	-0.54	12	17
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	0.018	0.11	0.27	1	-0.5	10	11
ADCY4	0.004	0.12	0.34	1	-0.39	4	5
ADCY5	-0.01	0.14	0.35	2	-0.49	14	16
ADCY6	0.003	0.12	0.34	1	-0.43	4	5
ADCY7	-0.005	0.13	0.34	1	-0.42	8	9
ADCY1	-0.004	0.12	0.34	1	-0.44	6	7
ADCY2	-0.056	0.15	0.35	1	-0.4	27	28
ADCY3	0.006	0.12	0.35	2	-0.43	4	6
ADCY8	-0.076	0.16	0.34	1	-0.45	25	26
ADCY9	0.004	0.12	0.35	2	-0.43	4	6
arachidonic acid secretion	0.036	0.14	0.36	7	-0.55	12	19
ETB receptor/Endothelin-1/Gq/GTP	0.024	0.08	-10000	0	-0.51	5	5
GNAO1	0.023	0.05	-10000	0	-0.53	4	4
HRAS	0.028	0.024	-10000	0	-0.5	1	1
ETA receptor/Endothelin-1/G12/GTP	0.037	0.16	0.4	19	-0.47	4	23
ETA receptor/Endothelin-1/Gs/GTP	0.038	0.16	0.38	22	-0.41	6	28
mol:GTP	0.002	0.002	-10000	0	-10000	0	0
COL3A1	-0.019	0.2	0.44	1	-0.56	48	49
EDNRB	0.017	0.053	-10000	0	-0.47	3	3
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.022	0.2	0.63	1	-0.49	39	40
CYSLTR1	0.003	0.15	0.44	1	-0.52	5	6
SLC9A1	0.013	0.089	0.28	2	-0.31	4	6
mol:GDP	0.02	0.14	0.32	7	-0.57	13	20
SLC9A3	-0.33	0.28	0.38	1	-0.65	130	131
RAF1	0.011	0.14	0.33	4	-0.62	11	15
JUN	0.042	0.14	-10000	0	-0.67	5	5
JAK2	0.003	0.15	0.37	2	-0.49	5	7
mol:IP3	0.013	0.12	0.25	1	-0.56	10	11
ETA receptor/Endothelin-1	0.027	0.21	0.45	27	-0.53	7	34
PLCB1	0.02	0.075	-10000	0	-0.61	7	7
PLCB2	-0.031	0.17	-10000	0	-0.5	58	58
ETA receptor/Endothelin-3	0.022	0.096	-10000	0	-0.37	11	11
FOS	0.022	0.18	0.39	4	-0.81	16	20
Gai/GDP	-0.11	0.26	-10000	0	-0.56	90	90
CRK	0.028	0.005	-10000	0	-10000	0	0
mol:Ca ++	0.001	0.16	0.32	1	-0.57	12	13
BCAR1	0.027	0.029	-10000	0	-0.61	1	1
PRKCB1	0.013	0.12	0.24	1	-0.53	10	11
GNAQ	0.03	0.007	-10000	0	-10000	0	0
GNAZ	0.025	0.049	-10000	0	-0.61	3	3
GNAL	0.028	0.005	-10000	0	-10000	0	0
Gs family/GDP	0.025	0.13	0.29	5	-0.54	11	16
ETA receptor/Endothelin-1/Gq/GTP	0.032	0.1	0.23	1	-0.51	4	5
MAPK14	0.012	0.095	0.33	1	-0.47	10	11
TRPC6	0.041	0.14	0.47	2	-0.71	6	8
GNAI2	0.02	0.013	-10000	0	-10000	0	0
GNAI3	0.028	0.005	-10000	0	-10000	0	0
GNAI1	0.024	0.03	-10000	0	-0.61	1	1
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	0.012	0.1	-10000	0	-0.49	11	11
ETB receptor/Endothelin-2	-0.02	0.14	-10000	0	-0.39	60	60
ETB receptor/Endothelin-3	0.02	0.07	-10000	0	-0.37	13	13
ETB receptor/Endothelin-1	0.015	0.12	-10000	0	-0.36	16	16
MAPK3	0.025	0.17	0.38	5	-0.72	16	21
MAPK1	0.025	0.17	0.39	5	-0.7	17	22
Rac1/GDP	0.021	0.13	0.3	2	-0.55	11	13
cAMP biosynthetic process	-0.017	0.14	0.36	9	-0.48	8	17
MAPK8	0.039	0.16	0.4	1	-0.67	12	13
SRC	0.028	0.006	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	0.01	0.072	-10000	0	-0.45	5	5
p130Cas/CRK/Src/PYK2	0.034	0.14	0.42	9	-0.6	9	18
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	0.021	0.13	0.3	2	-0.55	11	13
COL1A2	-0.017	0.21	0.7	1	-0.54	50	51
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.017	0.15	0.3	1	-0.38	59	60
mol:DAG	0.013	0.12	0.25	1	-0.56	10	11
MAP2K2	0.022	0.15	0.46	3	-0.58	18	21
MAP2K1	0.024	0.15	0.37	5	-0.58	17	22
EDNRA	0.021	0.11	0.43	1	-0.4	2	3
positive regulation of muscle contraction	0.021	0.14	0.42	7	-0.41	4	11
Gq family/GDP	0.033	0.14	-10000	0	-0.55	12	12
HRAS/GTP	0.016	0.14	0.29	7	-0.58	12	19
PRKCH	0.013	0.11	-10000	0	-0.55	8	8
RAC1	0.026	0.009	-10000	0	-10000	0	0
PRKCA	0.016	0.12	0.24	4	-0.56	9	13
PRKCB	0.016	0.13	0.28	14	-0.55	13	27
PRKCE	0.015	0.12	0.24	5	-0.53	10	15
PRKCD	0	0.11	-10000	0	-0.55	9	9
PRKCG	0	0.13	-10000	0	-0.59	12	12
regulation of vascular smooth muscle contraction	0.02	0.2	0.42	5	-0.93	16	21
PRKCQ	0.007	0.13	0.28	1	-0.61	11	12
PLA2G4A	0.035	0.15	0.37	7	-0.6	12	19
GNA14	0.023	0.069	-10000	0	-0.61	6	6
GNA15	0.015	0.09	-10000	0	-0.5	15	15
GNA12	0.026	0.009	-10000	0	-10000	0	0
GNA11	0.027	0.049	-10000	0	-0.61	3	3
Rac1/GTP	0.038	0.16	0.4	19	-0.47	4	23
MMP1	-0.097	0.26	0.65	1	-0.58	91	92

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.036	0.084	-10000	0	-0.34	21	21
NF kappa B1 p50/RelA/I kappa B alpha	0.046	0.077	0.28	2	-10000	0	2
AP1	0.019	0.091	-10000	0	-0.34	8	8
mol:PIP3	0	0.063	-10000	0	-0.47	1	1
AKT1	0.004	0.11	0.31	4	-0.38	10	14
PTK2B	0.002	0.085	0.22	2	-0.35	11	13
RHOA	-0.044	0.12	-10000	0	-0.35	24	24
PIK3CB	0.027	0.007	-10000	0	-10000	0	0
mol:Ca2+	0.025	0.057	0.42	2	-0.38	2	4
MAGI3	0.025	0.04	-10000	0	-0.61	2	2
RELA	0.029	0.003	-10000	0	-10000	0	0
apoptosis	0.008	0.074	-10000	0	-0.32	22	22
HRAS/GDP	0.02	0.017	-10000	0	-0.36	1	1
positive regulation of microtubule depolymerization	0.006	0.086	0.26	8	-0.32	12	20
NF kappa B1 p50/RelA	0.024	0.075	-10000	0	-0.39	1	1
endothelial cell migration	0.005	0.094	-10000	0	-0.4	25	25
ADCY4	0.003	0.098	-10000	0	-0.44	20	20
ADCY5	-0.003	0.11	-10000	0	-0.42	26	26
ADCY6	0.003	0.097	-10000	0	-0.44	20	20
ADCY7	0	0.098	-10000	0	-0.44	20	20
ADCY1	-0.001	0.096	0.21	1	-0.43	21	22
ADCY2	-0.02	0.11	-10000	0	-0.43	24	24
ADCY3	0.003	0.097	-10000	0	-0.43	21	21
ADCY8	-0.027	0.11	0.21	1	-0.42	27	28
ADCY9	0.002	0.096	-10000	0	-0.44	20	20
GSK3B	0.005	0.082	0.26	5	-0.37	8	13
arachidonic acid secretion	0.003	0.099	-10000	0	-0.42	22	22
GNG2	0.027	0.008	-10000	0	-10000	0	0
TRIP6	0.026	0.011	-10000	0	-10000	0	0
GNAO1	0.006	0.088	-10000	0	-0.36	25	25
HRAS	0.028	0.024	-10000	0	-0.5	1	1
NFKBIA	0.025	0.077	0.33	5	-0.38	2	7
GAB1	0.028	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	0.013	0.17	-10000	0	-0.83	19	19
JUN	0.028	0.006	-10000	0	-10000	0	0
LPA/LPA2/NHERF2	0.038	0.024	-10000	0	-0.38	1	1
TIAM1	-0.004	0.2	-10000	0	-0.98	20	20
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
mol:IP3	0.024	0.057	0.42	2	-0.39	2	4
PLCB3	0.032	0.039	-10000	0	-0.35	1	1
FOS	0.012	0.096	-10000	0	-0.6	12	12
positive regulation of mitosis	0.003	0.099	-10000	0	-0.42	22	22
LPA/LPA1-2-3	0.034	0.088	-10000	0	-0.34	24	24
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0	-10000	0	-10000	0	0
BCAR1	0.027	0.029	-10000	0	-0.61	1	1
stress fiber formation	0.015	0.085	0.31	2	-0.36	7	9
GNAZ	0.007	0.089	-10000	0	-0.38	24	24
EGFR/PI3K-beta/Gab1	0.01	0.069	-10000	0	-0.5	1	1
positive regulation of dendritic cell cytokine production	0.032	0.087	-10000	0	-0.33	24	24
LPA/LPA2/MAGI-3	0.037	0.031	-10000	0	-0.38	2	2
ARHGEF1	0.031	0.088	0.36	6	-0.32	14	20
GNAI2	0.003	0.079	-10000	0	-0.36	21	21
GNAI3	0.008	0.084	-10000	0	-0.37	22	22
GNAI1	0.008	0.078	-10000	0	-0.36	19	19
LPA/LPA3	0.017	0.033	-10000	0	-0.36	3	3
LPA/LPA2	0.023	0.014	-10000	0	-0.17	1	1
LPA/LPA1	0.006	0.098	-10000	0	-0.4	26	26
HB-EGF/EGFR	-0.1	0.16	-10000	0	-0.31	178	178
HBEGF	-0.13	0.18	-10000	0	-0.36	184	184
mol:DAG	0.024	0.057	0.42	2	-0.39	2	4
cAMP biosynthetic process	0.008	0.11	0.36	10	-0.39	21	31
NFKB1	0.027	0.029	-10000	0	-0.61	1	1
SRC	0.028	0.006	-10000	0	-10000	0	0
GNB1	0.027	0.006	-10000	0	-10000	0	0
LYN	0.028	0.08	0.33	7	-0.38	3	10
GNAQ	0.02	0.023	-10000	0	-10000	0	0
LPAR2	0.029	0.003	-10000	0	-10000	0	0
LPAR3	0.02	0.041	-10000	0	-0.5	3	3
LPAR1	0.004	0.12	-10000	0	-0.57	22	22
IL8	-0.024	0.14	0.29	1	-0.48	9	10
PTK2	0.011	0.077	-10000	0	-0.32	20	20
Rac1/GDP	0.019	0.007	-10000	0	-10000	0	0
CASP3	0.008	0.075	-10000	0	-0.32	22	22
EGFR	0.019	0.06	-10000	0	-0.52	6	6
PLCG1	0.018	0.037	-10000	0	-0.43	1	1
PLD2	0.012	0.077	-10000	0	-0.32	20	20
G12/G13	0.037	0.075	-10000	0	-0.34	14	14
PI3K-beta	-0.026	0.1	-10000	0	-0.43	10	10
cell migration	0.024	0.064	-10000	0	-0.26	13	13
SLC9A3R2	0.026	0.029	-10000	0	-0.61	1	1
PXN	0.015	0.086	0.31	2	-0.36	7	9
HRAS/GTP	0.003	0.099	-10000	0	-0.44	21	21
RAC1	0.026	0.009	-10000	0	-10000	0	0
MMP9	-0.21	0.26	-10000	0	-0.5	230	230
PRKCE	0.027	0.029	-10000	0	-0.61	1	1
PRKCD	0.021	0.06	0.36	4	-0.37	2	6
Gi(beta/gamma)	0.007	0.095	-10000	0	-0.41	22	22
mol:LPA	-0.002	0.019	-10000	0	-0.22	2	2
TRIP6/p130 Cas/FAK1/Paxillin	0.031	0.085	-10000	0	-10000	0	0
MAPKKK cascade	0.003	0.099	-10000	0	-0.42	22	22
contractile ring contraction involved in cytokinesis	-0.046	0.12	-10000	0	-0.36	22	22
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	0.016	0.046	-10000	0	-0.38	5	5
GNA15	0.014	0.045	-10000	0	-0.38	1	1
GNA12	0.026	0.009	-10000	0	-10000	0	0
GNA13	0.028	0.005	-10000	0	-10000	0	0
MAPT	0.005	0.088	0.26	7	-0.32	13	20
GNA11	0.019	0.034	-10000	0	-0.32	3	3
Rac1/GTP	0.012	0.18	-10000	0	-0.88	19	19
MMP2	0.005	0.095	-10000	0	-0.4	25	25

Presenilin action in Notch and Wnt signaling

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
Delta 1/NOTCH/NOTCH(cleaved)	0.034	0.079	-10000	0	-0.62	1	1
HDAC1	0.025	0.007	-10000	0	-10000	0	0
AES	0.028	0.003	-10000	0	-10000	0	0
FBXW11	0.022	0.013	-10000	0	-10000	0	0
DTX1	-0.028	0.18	-10000	0	-0.6	45	45
LRP6/FZD1	0.037	0.014	-10000	0	-10000	0	0
TLE1	0.027	0.006	-10000	0	-10000	0	0
AP1	-0.066	0.15	-10000	0	-0.31	133	133
NCSTN	0.027	0.006	-10000	0	-10000	0	0
ADAM10	0.027	0.028	-10000	0	-0.61	1	1
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.042	0.057	-10000	0	-0.74	1	1
NICD/RBPSUH	0.036	0.079	-10000	0	-0.61	1	1
WIF1	0.016	0.061	-10000	0	-0.59	5	5
NOTCH1	0.02	0.08	-10000	0	-0.64	1	1
PSENEN	0.029	0.003	-10000	0	-10000	0	0
KREMEN2	-0.034	0.17	-10000	0	-0.5	58	58
DKK1	0.005	0.11	-10000	0	-0.54	21	21
beta catenin/beta TrCP1	0.033	0.089	0.29	4	-10000	0	4
APH1B	0.029	0.003	-10000	0	-10000	0	0
APH1A	0.027	0.006	-10000	0	-10000	0	0
AXIN1	0.011	0.067	0.27	6	-0.3	2	8
CtBP/CBP/TCF1/TLE1/AES	0.025	0.036	-10000	0	-0.35	2	2
PSEN1	0.027	0.008	-10000	0	-10000	0	0
FOS	0.012	0.096	-10000	0	-0.6	12	12
JUN	0.028	0.006	-10000	0	-10000	0	0
MAP3K7	0.026	0.007	-10000	0	-10000	0	0
CTNNB1	0.033	0.11	0.28	15	-0.33	4	19
MAPK3	0.028	0.006	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.001	0.13	-10000	0	-0.32	72	72
HNF1A	0.022	0.057	-10000	0	-0.61	4	4
CTBP1	0.028	0.004	-10000	0	-10000	0	0
MYC	0.009	0.12	-10000	0	-0.76	8	8
NKD1	-0.13	0.28	-10000	0	-0.6	130	130
FZD1	0.026	0.009	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	0.006	0.12	-10000	0	-0.6	4	4
apoptosis	-0.065	0.15	-10000	0	-0.31	133	133
Delta 1/NOTCHprecursor	0.033	0.079	-10000	0	-0.61	1	1
DLL1	0.026	0.008	-10000	0	-10000	0	0
PPARD	0.008	0.15	-10000	0	-0.75	18	18
Gamma Secretase	0.076	0.029	-10000	0	-10000	0	0
APC	0.011	0.073	0.28	6	-0.4	3	9
DVL1	0.018	0.034	-10000	0	-0.42	2	2
CSNK2A1	0.028	0.005	-10000	0	-10000	0	0
MAP3K7IP1	-0.001	0.003	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	0	0.14	-10000	0	-0.33	66	66
LRP6	0.028	0.005	-10000	0	-10000	0	0
CSNK1A1	0.022	0.013	-10000	0	-10000	0	0
NLK	0.016	0.007	-10000	0	-10000	0	0
CCND1	0.021	0.087	-10000	0	-0.72	2	2
WNT1	0.001	0.12	-10000	0	-0.5	25	25
Axin1/APC/beta catenin	0.077	0.099	0.36	22	-10000	0	22
DKK2	0.003	0.12	-10000	0	-0.54	23	23
NOTCH1 precursor/DVL1	0.042	0.081	-10000	0	-0.55	1	1
GSK3B	0.027	0.008	-10000	0	-10000	0	0
FRAT1	0.027	0.006	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	0.008	0.12	-10000	0	-0.6	4	4
PPP2R5D	0.082	0.15	0.33	116	-0.39	8	124
MAPK1	0.028	0.004	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.041	0.085	-10000	0	-0.35	4	4
RBPJ	0.028	0.004	-10000	0	-10000	0	0
CREBBP	0.03	0.008	-10000	0	-10000	0	0

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.063	0.14	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0.001	-10000	0	-10000	0	0
CRKL	0.028	0.004	-10000	0	-10000	0	0
STAT1 (dimer)/Cbp/p300	-0.038	0.13	0.32	2	-0.66	1	3
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.007	0.058	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.055	0.081	-10000	0	-0.29	3	3
CaM/Ca2+	-0.057	0.14	-10000	0	-10000	0	0
RAP1A	0.028	0.005	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	-0.068	0.12	-10000	0	-0.55	1	1
AKT1	-0.044	0.14	0.36	12	-10000	0	12
MAP2K1	-0.062	0.12	0.3	6	-10000	0	6
MAP3K11	-0.07	0.13	0.3	10	-0.52	1	11
IFNGR1	0.005	0.03	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.16	0.24	-10000	0	-0.51	136	136
Rap1/GTP	-0.06	0.095	-10000	0	-10000	0	0
CRKL/C3G	0.041	0.009	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.068	0.16	-10000	0	-10000	0	0
CEBPB	0.001	0.14	0.51	10	-10000	0	10
STAT3	0.028	0.004	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.046	0.15	-10000	0	-0.66	1	1
STAT1	-0.067	0.13	0.31	11	-0.55	1	12
CALM1	0.027	0.008	-10000	0	-10000	0	0
IFN-gamma (dimer)	-0.21	0.26	-10000	0	-0.5	230	230
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
STAT1 (dimer)/PIAS1	-0.054	0.13	0.31	6	-0.52	1	7
CEBPB/PTGES2/Cbp/p300	-0.003	0.074	-10000	0	-0.38	1	1
mol:Ca2+	-0.064	0.14	-10000	0	-10000	0	0
MAPK3	-0.029	0.11	0.42	3	-0.63	1	4
STAT1 (dimer)	-0.069	0.11	-10000	0	-0.42	2	2
MAPK1	-0.028	0.12	0.45	4	-0.6	2	6
JAK2	0.005	0.029	-10000	0	-10000	0	0
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
JAK1	0.005	0.03	-10000	0	-10000	0	0
CAMK2D	0.028	0.004	-10000	0	-10000	0	0
DAPK1	0.011	0.12	0.42	14	-0.61	3	17
SMAD7	-0.011	0.073	0.23	19	-10000	0	19
CBL/CRKL/C3G	-0.048	0.13	0.3	9	-10000	0	9
PI3K	-0.055	0.13	-10000	0	-10000	0	0
IFNG	-0.21	0.26	-10000	0	-0.5	230	230
apoptosis	0.004	0.12	0.4	14	-0.44	7	21
CAMK2G	0.028	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	0.028	0.004	-10000	0	-10000	0	0
CAMK2A	-0.13	0.27	-10000	0	-0.61	122	122
CAMK2B	-0.062	0.22	-10000	0	-0.6	71	71
FRAP1	-0.046	0.13	0.35	12	-10000	0	12
PRKCD	-0.055	0.12	0.33	10	-10000	0	10
RAP1B	0.028	0.005	-10000	0	-10000	0	0
negative regulation of cell growth	-0.055	0.081	-10000	0	-0.29	3	3
PTPN2	0.028	0.005	-10000	0	-10000	0	0
EP300	0.028	0.029	-10000	0	-0.61	1	1
IRF1	-0.03	0.1	0.41	5	-0.66	1	6
STAT1 (dimer)/PIASy	-0.057	0.13	0.33	5	-0.52	1	6
SOCS1	0.027	0.063	-10000	0	-0.99	1	1
mol:GDP	-0.048	0.13	0.28	6	-10000	0	6
CASP1	-0.011	0.073	0.23	19	-10000	0	19
PTGES2	0.025	0.04	-10000	0	-0.61	2	2
IRF9	0.022	0.065	0.24	18	-10000	0	18
mol:PI-3-4-5-P3	-0.061	0.12	-10000	0	-10000	0	0
RAP1/GDP	-0.049	0.11	-10000	0	-10000	0	0
CBL	-0.071	0.13	0.3	10	-0.32	1	11
MAP3K1	-0.067	0.12	0.32	6	-10000	0	6
PIAS1	0.029	0.003	-10000	0	-10000	0	0
PIAS4	0.028	0.003	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.055	0.081	-10000	0	-0.29	3	3
PTPN11	-0.079	0.13	-10000	0	-10000	0	0
CREBBP	0.028	0.006	-10000	0	-10000	0	0
RAPGEF1	0.028	0.005	-10000	0	-10000	0	0

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	0.011	0.055	-10000	0	-0.29	13	13
epithelial cell differentiation	0.027	0.067	-10000	0	-0.32	13	13
CYFIP2	0.013	0.075	-10000	0	-0.61	7	7
ENAH	0.056	0.1	0.38	17	-10000	0	17
EGFR	0.019	0.06	-10000	0	-0.52	6	6
EPHA2	0.026	0.029	-10000	0	-0.61	1	1
MYO6	0.055	0.11	0.38	13	-0.45	2	15
CTNNB1	0.02	0.013	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.036	0.056	-10000	0	-0.38	7	7
AQP5	-0.11	0.24	-10000	0	-0.5	108	108
CTNND1	0.029	0.003	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.059	0.11	0.39	13	-10000	0	13
regulation of calcium-dependent cell-cell adhesion	0.05	0.11	0.4	11	-0.39	1	12
EGF	-0.54	0.19	-10000	0	-0.61	460	460
NCKAP1	0.028	0.006	-10000	0	-10000	0	0
AQP3	0.004	0.15	-10000	0	-0.53	29	29
cortical microtubule organization	0.027	0.067	-10000	0	-0.32	13	13
GO:0000145	0.049	0.1	0.39	13	-10000	0	13
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.03	0.069	-10000	0	-0.33	13	13
MLLT4	0.026	0.008	-10000	0	-10000	0	0
ARF6/GDP	-0.008	0.044	-10000	0	-10000	0	0
ARF6	0.027	0.008	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.062	0.039	-10000	0	-0.35	2	2
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.037	0.081	0.37	2	-10000	0	2
PVRL2	0.029	0.003	-10000	0	-10000	0	0
ZYX	0.045	0.092	0.36	5	-10000	0	5
ARF6/GTP	0.066	0.042	-10000	0	-10000	0	0
CDH1	0.007	0.11	-10000	0	-0.59	17	17
EGFR/EGFR/EGF/EGF	-0.23	0.14	-10000	0	-0.55	18	18
RhoA/GDP	0.028	0.064	-10000	0	-10000	0	0
actin cytoskeleton organization	0.047	0.1	0.34	12	-0.42	2	14
IGF-1R heterotetramer	0.029	0.003	-10000	0	-10000	0	0
GIT1	0.028	0.004	-10000	0	-10000	0	0
IGF1R	0.029	0.003	-10000	0	-10000	0	0
IGF1	0.023	0.053	-10000	0	-0.5	5	5
DIAPH1	0.029	0.11	-10000	0	-0.66	7	7
Wnt receptor signaling pathway	-0.027	0.067	0.32	13	-10000	0	13
RHOA	0.021	0.013	-10000	0	-10000	0	0
RhoA/GTP	-0.008	0.045	-10000	0	-10000	0	0
CTNNA1	0.022	0.012	-10000	0	-10000	0	0
VCL	0.048	0.1	0.35	12	-0.43	2	14
EFNA1	0.026	0.024	-10000	0	-0.5	1	1
LPP	0.043	0.092	0.39	6	-10000	0	6
Ephrin A1/EPHA2	0.022	0.061	-10000	0	-10000	0	0
SEC6/SEC8	0.001	0.047	-10000	0	-10000	0	0
MGAT3	0.05	0.11	0.41	11	-0.4	1	12
HGF/MET	0.013	0.083	-10000	0	-0.52	3	3
HGF	0.003	0.11	-10000	0	-0.54	20	20
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.011	0.056	-10000	0	-0.29	13	13
actin cable formation	0.098	0.13	0.32	72	-10000	0	72
KIAA1543	0.045	0.1	0.35	10	-0.5	2	12
KIFC3	0.048	0.092	-10000	0	-10000	0	0
NCK1	0.026	0.029	-10000	0	-0.61	1	1
EXOC3	0.026	0.009	-10000	0	-10000	0	0
ACTN1	0.05	0.099	0.43	7	-10000	0	7
NCK1/GIT1	0.039	0.025	-10000	0	-0.45	1	1
mol:GDP	0.027	0.067	-10000	0	-0.32	13	13
EXOC4	0.026	0.009	-10000	0	-10000	0	0
STX4	0.048	0.09	-10000	0	-10000	0	0
PIP5K1C	0.059	0.11	0.4	13	-10000	0	13
LIMA1	0.028	0.005	-10000	0	-10000	0	0
ABI1	0.028	0.004	-10000	0	-10000	0	0
ROCK1	0.068	0.11	0.4	20	-10000	0	20
adherens junction assembly	0.067	0.14	0.5	16	-0.7	2	18
IGF-1R heterotetramer/IGF1	0.022	0.064	-10000	0	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.039	0.013	-10000	0	-10000	0	0
MET	0.024	0.034	-10000	0	-0.5	2	2
PLEKHA7	0.055	0.1	0.36	10	-0.53	2	12
mol:GTP	0.06	0.038	-10000	0	-0.35	2	2
establishment of epithelial cell apical/basal polarity	0.077	0.13	0.37	49	-10000	0	49
cortical actin cytoskeleton stabilization	0.011	0.055	-10000	0	-0.29	13	13
regulation of cell-cell adhesion	0.047	0.1	0.34	12	-0.42	2	14
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.011	0.056	-10000	0	-0.29	13	13

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.037	0.14	-10000	0	-0.53	14	14
Crk/p130 Cas/Paxillin	-0.029	0.081	-10000	0	-0.41	5	5
JUN	0.005	0.086	-10000	0	-0.45	7	7
HRAS	0.028	0.024	-10000	0	-0.5	1	1
RET51/GFRalpha1/GDNF/GRB10	0.021	0.12	-10000	0	-0.37	33	33
RAP1A	0.028	0.005	-10000	0	-10000	0	0
FRS2	0.028	0.005	-10000	0	-10000	0	0
RAP1A/GDP	0.021	0.004	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	0.021	0.12	-10000	0	-0.37	41	41
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.028	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.028	0.005	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	0.012	0.09	-10000	0	-0.33	26	26
RHOA	0.021	0.013	-10000	0	-10000	0	0
RAP1A/GTP	0.021	0.11	-10000	0	-0.34	35	35
GRB7	0.021	0.069	-10000	0	-0.61	6	6
RET51/GFRalpha1/GDNF	0.022	0.12	-10000	0	-0.37	38	38
MAPKKK cascade	0.01	0.1	-10000	0	-0.47	4	4
BCAR1	0.027	0.029	-10000	0	-0.61	1	1
RET9/GFRalpha1/GDNF/IRS1	0.014	0.1	-10000	0	-0.35	35	35
lamellipodium assembly	0.001	0.086	-10000	0	-0.29	25	25
RET51/GFRalpha1/GDNF/SHC	0.021	0.12	-10000	0	-0.37	39	39
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
RET9/GFRalpha1/GDNF/SHC	0.018	0.096	-10000	0	-0.34	30	30
RET9/GFRalpha1/GDNF/Shank3	0.018	0.098	-10000	0	-0.34	32	32
MAPK3	0.004	0.11	0.52	1	-0.53	3	4
DOK1	0.028	0.005	-10000	0	-10000	0	0
DOK6	0.015	0.09	-10000	0	-0.58	11	11
PXN	0.028	0.005	-10000	0	-10000	0	0
neurite development	0.002	0.1	-10000	0	-0.45	6	6
DOK5	0.015	0.087	-10000	0	-0.6	10	10
GFRA1	-0.013	0.15	-10000	0	-0.55	36	36
MAPK8	0	0.091	-10000	0	-0.43	11	11
HRAS/GTP	0.019	0.12	-10000	0	-0.37	33	33
tube development	0.021	0.096	-10000	0	-0.34	26	26
MAPK1	0.009	0.12	0.43	6	-0.53	3	9
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	0.008	0.069	-10000	0	-0.27	22	22
Rac1/GDP	0.019	0.007	-10000	0	-10000	0	0
SRC	0.028	0.006	-10000	0	-10000	0	0
PDLIM7	0.018	0.042	-10000	0	-0.5	3	3
RET51/GFRalpha1/GDNF/Dok6	0.026	0.14	-10000	0	-0.39	39	39
SHC1	0.027	0.006	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	0.021	0.12	-10000	0	-0.37	37	37
RET51/GFRalpha1/GDNF/Dok5	0.016	0.14	-10000	0	-0.42	39	39
PRKCA	0.028	0.005	-10000	0	-10000	0	0
HRAS/GDP	0.02	0.017	-10000	0	-0.36	1	1
CREB1	0.005	0.092	-10000	0	-0.43	9	9
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	0.006	0.077	-10000	0	-0.29	27	27
RET51/GFRalpha1/GDNF/Grb7	0.017	0.14	-10000	0	-0.41	40	40
mol:GDP	0	0	-10000	0	-10000	0	0
RET	0.007	0.11	-10000	0	-0.58	18	18
DOK4	0.028	0.006	-10000	0	-10000	0	0
JNK cascade	0.004	0.087	-10000	0	-0.43	8	8
RET9/GFRalpha1/GDNF/FRS2	0.019	0.094	-10000	0	-0.34	28	28
SHANK3	0.028	0.004	-10000	0	-10000	0	0
RASA1	0.024	0.03	-10000	0	-0.61	1	1
NCK1	0.026	0.029	-10000	0	-0.61	1	1
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	0.005	0.08	-10000	0	-0.3	28	28
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	0.004	0.09	-10000	0	-0.37	8	8
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	0.001	0.1	-10000	0	-0.32	40	40
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	0.003	0.097	-10000	0	-0.44	10	10
PI3K	0.002	0.13	-10000	0	-0.44	28	28
SOS1	0.028	0.005	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	0.029	0.097	-10000	0	-0.34	26	26
GRB10	0.026	0.009	-10000	0	-10000	0	0
activation of MAPKK activity	0.004	0.08	-10000	0	-0.39	3	3
RET51/GFRalpha1/GDNF/FRS2	0.023	0.12	-10000	0	-0.38	35	35
GAB1	0.028	0.004	-10000	0	-10000	0	0
IRS1	0.022	0.057	-10000	0	-0.61	4	4
IRS2	0.02	0.068	-10000	0	-0.52	8	8
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	0.001	0.1	-10000	0	-0.4	15	15
RET51/GFRalpha1/GDNF/PKC alpha	0.021	0.12	-10000	0	-0.37	38	38
GRB2	0.028	0.005	-10000	0	-10000	0	0
PRKACA	0.029	0.002	-10000	0	-10000	0	0
GDNF	0.017	0.041	-10000	0	-0.5	3	3
RAC1	0.026	0.009	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	0.017	0.13	-10000	0	-0.37	45	45
Rac1/GTP	0.009	0.1	-10000	0	-0.35	24	24
RET9/GFRalpha1/GDNF	0.002	0.1	-10000	0	-0.37	33	33
GFRalpha1/GDNF	0	0.12	-10000	0	-0.44	33	33

IL6-mediated signaling events

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
BCL2L1	-0.079	0.22	0.54	4	-0.66	6	10
CRP	-0.11	0.26	0.5	2	-0.62	45	47
cell cycle arrest	-0.1	0.23	-10000	0	-0.62	29	29
TIMP1	-0.08	0.22	0.45	1	-0.59	32	33
IL6ST	0.005	0.11	-10000	0	-0.61	15	15
Rac1/GDP	-0.07	0.15	-10000	0	-0.42	28	28
AP1	0.026	0.12	0.45	1	-0.74	4	5
GAB2	0.028	0.003	-10000	0	-10000	0	0
TNFSF11	-0.11	0.24	0.59	1	-0.66	30	31
HSP90B1	0.026	0.058	-10000	0	-10000	0	0
GAB1	0.029	0.004	-10000	0	-10000	0	0
MAPK14	0.005	0.093	-10000	0	-0.53	4	4
AKT1	0.04	0.04	-10000	0	-0.5	1	1
FOXO1	0.047	0.045	-10000	0	-0.48	1	1
MAP2K6	-0.015	0.093	-10000	0	-0.58	4	4
mol:GTP	-0.001	0.003	-10000	0	-10000	0	0
MAP2K4	-0.084	0.16	-10000	0	-0.44	33	33
MITF	-0.023	0.093	-10000	0	-0.46	6	6
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.029	0.003	-10000	0	-10000	0	0
A2M	0.029	0.051	-10000	0	-1.1	1	1
CEBPB	0.023	0.067	-10000	0	-0.5	8	8
GRB2/SOS1/GAB family/SHP2	0.013	0.079	-10000	0	-0.76	3	3
STAT3	-0.12	0.22	-10000	0	-0.65	28	28
STAT1	-0.002	0.11	-10000	0	-0.76	9	9
CEBPD	-0.081	0.21	0.53	2	-0.66	6	8
PIK3CA	0.027	0.029	-10000	0	-0.61	1	1
PI3K	0.038	0.034	-10000	0	-0.45	2	2
JUN	0.027	0.006	-10000	0	-10000	0	0
PIAS3/MITF	-0.01	0.099	-10000	0	-0.56	3	3
MAPK11	0.005	0.095	-10000	0	-0.52	5	5
STAT3 (dimer)/FOXO1	-0.054	0.18	0.41	1	-0.62	4	5
GRB2/SOS1/GAB family	0.03	0.11	-10000	0	-0.56	2	2
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.015	0.1	-10000	0	-0.39	13	13
GRB2	0.028	0.005	-10000	0	-10000	0	0
JAK2	0.027	0.007	-10000	0	-10000	0	0
LBP	-0.2	0.38	0.53	4	-0.79	119	123
PIK3R1	0.026	0.03	-10000	0	-0.61	1	1
JAK1	0.027	0.01	-10000	0	-10000	0	0
MYC	-0.086	0.22	0.52	3	-0.68	9	12
FGG	-0.15	0.27	0.51	1	-0.65	46	47
macrophage differentiation	-0.1	0.23	-10000	0	-0.62	29	29
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0.01	0.13	-10000	0	-0.37	17	17
JUNB	-0.085	0.21	-10000	0	-0.75	8	8
FOS	0.011	0.096	-10000	0	-0.6	12	12
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.023	0.1	-10000	0	-0.46	7	7
STAT1/PIAS1	-0.024	0.12	-10000	0	-0.51	5	5
GRB2/SOS1/GAB family/SHP2/PI3K	0.038	0.043	-10000	0	-0.53	1	1
STAT3 (dimer)	-0.1	0.24	-10000	0	-0.65	29	29
PRKCD	-0.095	0.18	0.41	7	-0.49	32	39
IL6R	0.027	0.009	-10000	0	-10000	0	0
SOCS3	0.032	0.11	0.45	1	-0.66	2	3
gp130 (dimer)/JAK1/JAK1/LMO4	0.033	0.079	-10000	0	-0.38	15	15
Rac1/GTP	-0.077	0.16	-10000	0	-0.42	36	36
HCK	0	0.12	-10000	0	-0.5	26	26
MAPKKK cascade	0.031	0.095	-10000	0	-0.61	6	6
bone resorption	-0.1	0.24	0.59	1	-0.62	31	32
IRF1	-0.05	0.23	0.53	7	-0.62	10	17
mol:GDP	-0.085	0.15	-10000	0	-0.38	52	52
SOS1	0.027	0.005	-10000	0	-10000	0	0
VAV1	-0.086	0.15	-10000	0	-0.39	52	52
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	0.007	0.11	-10000	0	-0.57	6	6
PTPN11	0.011	0.038	-10000	0	-0.71	1	1
IL6/IL6RA	-0.017	0.14	-10000	0	-0.4	59	59
gp130 (dimer)/TYK2/TYK2/LMO4	0.035	0.077	-10000	0	-0.38	15	15
gp130 (dimer)/JAK2/JAK2/LMO4	0.033	0.077	-10000	0	-0.38	15	15
IL6	-0.045	0.19	-10000	0	-0.55	60	60
PIAS3	0.028	0.006	-10000	0	-10000	0	0
PTPRE	0.029	0.017	-10000	0	-10000	0	0
PIAS1	0.029	0.003	-10000	0	-10000	0	0
RAC1	0.025	0.009	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.016	0.093	-10000	0	-0.35	13	13
LMO4	0.024	0.016	-10000	0	-10000	0	0
STAT3 (dimer)/PIAS3	-0.1	0.22	-10000	0	-0.63	24	24
MCL1	0.053	0.057	-10000	0	-10000	0	0

Class I PI3K signaling events

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
ARF5/GTP	0.021	0.027	0.3	1	-10000	0	1
DAPP1	0.008	0.11	0.34	8	-0.42	10	18
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.06	0.17	0.36	2	-0.51	25	27
mol:DAG	-0.009	0.15	0.28	57	-0.25	13	70
HRAS	0.032	0.025	-10000	0	-0.5	1	1
RAP1A	0.032	0.009	-10000	0	-10000	0	0
ARF5/GDP	0.031	0.072	0.25	2	-0.39	4	6
PLCG2	0.02	0.068	-10000	0	-0.55	7	7
PLCG1	0.028	0.006	-10000	0	-10000	0	0
ARF5	0.026	0.009	-10000	0	-10000	0	0
mol:GTP	0.007	0.029	0.3	2	-10000	0	2
ARF1/GTP	0.034	0.057	0.31	3	-10000	0	3
RHOA	0.021	0.013	-10000	0	-10000	0	0
YES1	0.028	0.004	-10000	0	-10000	0	0
RAP1A/GTP	0.019	0.027	0.3	1	-10000	0	1
ADAP1	0.032	0.07	0.29	3	-10000	0	3
ARAP3	0.007	0.029	0.3	2	-10000	0	2
INPPL1	0.029	0.003	-10000	0	-10000	0	0
PREX1	0.028	0.006	-10000	0	-10000	0	0
ARHGEF6	0.029	0.003	-10000	0	-10000	0	0
ARHGEF7	0.028	0.004	-10000	0	-10000	0	0
ARF1	0.028	0.006	-10000	0	-10000	0	0
NRAS	0.032	0.009	-10000	0	-10000	0	0
FYN	0.027	0.008	-10000	0	-10000	0	0
ARF6	0.027	0.008	-10000	0	-10000	0	0
FGR	0.025	0.041	-10000	0	-0.5	3	3
mol:Ca2+	0.005	0.094	0.31	20	-10000	0	20
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.028	0.006	-10000	0	-10000	0	0
ZAP70	-0.26	0.26	-10000	0	-0.5	276	276
mol:IP3	-0.001	0.11	0.32	24	-10000	0	24
LYN	0.027	0.007	-10000	0	-10000	0	0
ARF1/GDP	0.042	0.077	0.25	7	-0.38	4	11
RhoA/GDP	0.016	0.044	0.38	1	-10000	0	1
PDK1/Src/Hsp90	0.05	0.028	-10000	0	-0.39	1	1
BLNK	0.026	0.029	-10000	0	-0.61	1	1
actin cytoskeleton reorganization	0.038	0.095	0.36	14	-10000	0	14
SRC	0.028	0.006	-10000	0	-10000	0	0
PLEKHA2	0.01	0.028	-10000	0	-0.3	4	4
RAC1	0.026	0.009	-10000	0	-10000	0	0
PTEN	0.017	0.017	-10000	0	-10000	0	0
HSP90AA1	0.027	0.008	-10000	0	-10000	0	0
ARF6/GTP	0.021	0.026	0.3	1	-10000	0	1
RhoA/GTP	0.016	0.029	0.3	2	-10000	0	2
Src family/SYK family/BLNK-LAT	-0.084	0.14	-10000	0	-0.43	27	27
BLK	-0.009	0.13	-10000	0	-0.5	33	33
PDPK1	0.026	0.029	-10000	0	-0.61	1	1
CYTH1	0.045	0.073	0.29	11	-10000	0	11
HCK	0.001	0.12	-10000	0	-0.5	26	26
CYTH3	0.034	0.063	0.29	3	-10000	0	3
CYTH2	0.044	0.073	0.29	11	-10000	0	11
KRAS	0.032	0.009	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.039	0.055	-10000	0	-0.38	1	1
SGK1	0.035	0.071	-10000	0	-0.41	1	1
INPP5D	0.023	0.047	-10000	0	-0.5	4	4
mol:GDP	0.031	0.079	0.23	12	-0.41	4	16
SOS1	0.028	0.005	-10000	0	-10000	0	0
SYK	0.026	0.032	-10000	0	-0.46	2	2
ARF6/GDP	0.016	0.043	0.32	2	-10000	0	2
mol:PI-3-4-5-P3	0.037	0.062	-10000	0	-10000	0	0
ARAP3/RAP1A/GTP	0.019	0.027	0.3	1	-10000	0	1
VAV1	-0.099	0.23	-10000	0	-0.5	122	122
mol:PI-3-4-P2	0.017	0.034	-10000	0	-0.36	4	4
RAS family/GTP/PI3K Class I	0.078	0.066	0.33	1	-10000	0	1
PLEKHA1	0.01	0.028	-10000	0	-0.3	4	4
Rac1/GDP	0.031	0.071	0.24	1	-0.39	4	5
LAT	-0.12	0.24	-10000	0	-0.5	141	141
Rac1/GTP	0.018	0.064	-10000	0	-0.41	1	1
ITK	-0.044	0.13	0.28	25	-10000	0	25
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.03	0.17	0.3	48	-0.33	36	84
LCK	0.004	0.11	-10000	0	-0.51	22	22
BTK	-0.007	0.14	0.29	12	-10000	0	12

Canonical Wnt signaling 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
HDAC1	0.025	0.011	-10000	0	-10000	0	0
AES	0.026	0.009	-10000	0	-10000	0	0
FBXW11	0.022	0.013	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
LRP6/FZD1	0.038	0.015	-10000	0	-10000	0	0
SMAD4	0.028	0.005	-10000	0	-10000	0	0
DKK2	0.003	0.12	-10000	0	-0.54	23	23
TLE1	0.026	0.01	-10000	0	-10000	0	0
MACF1	0.029	0.006	-10000	0	-10000	0	0
CTNNB1	0.036	0.11	0.38	13	-0.39	1	14
WIF1	0.002	0.063	-10000	0	-0.59	5	5
beta catenin/RanBP3	-0.004	0.082	0.34	5	-10000	0	5
KREMEN2	-0.034	0.17	-10000	0	-0.5	58	58
DKK1	0.005	0.11	-10000	0	-0.54	21	21
beta catenin/beta TrCP1	0.018	0.082	0.38	1	-0.36	1	2
FZD1	0.026	0.009	-10000	0	-10000	0	0
AXIN2	-0.003	0.12	0.55	9	-1.4	2	11
AXIN1	0.028	0.007	-10000	0	-10000	0	0
RAN	0.028	0.005	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.002	0.12	-10000	0	-0.52	17	17
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.057	0.085	0.31	2	-0.76	1	3
Axin1/APC/GSK3	0.071	0.085	0.3	25	-10000	0	25
Axin1/APC/GSK3/beta catenin/Macf1	0.048	0.096	0.36	10	-10000	0	10
HNF1A	0.021	0.057	-10000	0	-0.61	4	4
CTBP1	0.026	0.01	-10000	0	-10000	0	0
MYC	-0.001	0.12	0.59	12	-10000	0	12
RANBP3	0.028	0.003	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0	0.13	-10000	0	-0.32	72	72
NKD1	-0.13	0.28	-10000	0	-0.6	130	130
TCF4	0.026	0.01	-10000	0	-10000	0	0
TCF3	0.026	0.01	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0.046	0.077	-10000	0	-10000	0	0
Ran/GTP	0.02	0.004	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.012	0.083	0.39	6	-0.53	2	8
LEF1	0.01	0.091	-10000	0	-0.51	15	15
DVL1	0.019	0.029	-10000	0	-0.3	2	2
CSNK2A1	0.028	0.006	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.065	0.086	0.33	2	-0.61	2	4
DKK1/LRP6/Kremen 2	0	0.14	-10000	0	-0.33	66	66
LRP6	0.028	0.006	-10000	0	-10000	0	0
CSNK1A1	0.02	0.014	-10000	0	-10000	0	0
NLK	0.029	0.005	-10000	0	-10000	0	0
CCND1	-0.016	0.089	0.57	2	-0.47	1	3
WNT1	0.002	0.12	-10000	0	-0.5	25	25
GSK3A	0.03	0.004	-10000	0	-10000	0	0
GSK3B	0.027	0.008	-10000	0	-10000	0	0
FRAT1	0.027	0.006	-10000	0	-10000	0	0
PPP2R5D	0.094	0.14	0.32	121	-0.37	7	128
APC	0.026	0.088	0.38	9	-10000	0	9
WNT1/LRP6/FZD1	0.035	0.048	0.25	3	-10000	0	3
CREBBP	0.025	0.011	-10000	0	-10000	0	0

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.01	0.002	-10000	0	-10000	0	0
GNB1/GNG2	0.032	0.084	-10000	0	-0.34	23	23
regulation of S phase of mitotic cell cycle	0.017	0.066	-10000	0	-0.3	17	17
GNAO1	0.023	0.05	-10000	0	-0.53	4	4
HRAS	0.028	0.024	-10000	0	-0.5	1	1
SHBG/T-DHT	-0.023	0.12	-10000	0	-0.38	53	53
PELP1	0.028	0.005	-10000	0	-10000	0	0
AKT1	0.01	0.003	-10000	0	-10000	0	0
MAP2K1	0.006	0.068	0.35	1	-0.39	3	4
T-DHT/AR	-0.001	0.099	-10000	0	-0.44	24	24
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.002	-10000	0	-0.009	13	13
GNAI2	0.02	0.013	-10000	0	-10000	0	0
GNAI3	0.028	0.005	-10000	0	-10000	0	0
GNAI1	0.025	0.03	-10000	0	-0.61	1	1
mol:GDP	-0.007	0.096	-10000	0	-0.45	22	22
cell proliferation	-0.002	0.1	0.3	6	-0.48	10	16
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
FOS	0.003	0.14	-10000	0	-0.76	13	13
mol:Ca2+	0.002	0.015	-10000	0	-0.078	10	10
MAPK3	0.004	0.088	0.3	6	-0.47	5	11
MAPK1	0.008	0.064	-10000	0	-0.51	3	3
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
mol:IP3	0	0.001	-10000	0	-0.005	12	12
cAMP biosynthetic process	-0.038	0.11	0.24	2	-0.37	52	54
GNG2	0.027	0.008	-10000	0	-10000	0	0
potassium channel inhibitor activity	0	0.001	-10000	0	-0.005	12	12
HRAS/GTP	0.04	0.074	-10000	0	-0.32	18	18
actin cytoskeleton reorganization	0.034	0.029	-10000	0	-0.31	2	2
SRC	0.028	0.006	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.005	12	12
PI3K	0.033	0.029	-10000	0	-0.39	2	2
apoptosis	-0.008	0.1	0.5	12	-0.25	3	15
T-DHT/AR/PELP1	0.019	0.087	-10000	0	-0.38	22	22
HRAS/GDP	0.009	0.096	-10000	0	-0.43	22	22
CREB1	0.007	0.11	0.26	3	-0.54	12	15
RAC1-CDC42/GTP	0.043	0.032	-10000	0	-0.31	2	2
AR	-0.001	0.13	-10000	0	-0.6	24	24
GNB1	0.028	0.006	-10000	0	-10000	0	0
RAF1	0.009	0.071	0.35	1	-0.38	3	4
RAC1-CDC42/GDP	0.029	0.095	-10000	0	-0.42	19	19
T-DHT/AR/PELP1/Src	0.037	0.079	-10000	0	-0.35	18	18
MAP2K2	0.005	0.068	0.35	1	-0.39	3	4
T-DHT/AR/PELP1/Src/PI3K	0.017	0.067	-10000	0	-0.3	17	17
GNAZ	0.025	0.049	-10000	0	-0.61	3	3
SHBG	-0.038	0.19	-10000	0	-0.6	53	53
Gi family/GNB1/GNG2/GDP	-0.013	0.12	-10000	0	-0.48	16	16
mol:T-DHT	0	0.001	-10000	0	-0.007	9	9
RAC1	0.026	0.009	-10000	0	-10000	0	0
GNRH1	-0.095	0.17	0.19	1	-0.37	141	142
Gi family/GTP	0.006	0.055	-10000	0	-0.3	10	10
CDC42	0.028	0.006	-10000	0	-10000	0	0

Regulation of Androgen receptor activity

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	0.02	0.005	-10000	0	-10000	0	0
SMARCC1	0.006	0.046	-10000	0	-0.66	2	2
REL	0.025	0.043	-10000	0	-0.51	3	3
HDAC7	-0.13	0.093	-10000	0	-0.5	7	7
JUN	0.028	0.006	-10000	0	-10000	0	0
EP300	0.027	0.029	-10000	0	-0.61	1	1
KAT2B	0.019	0.031	-10000	0	-0.61	1	1
KAT5	0.029	0.003	-10000	0	-10000	0	0
MAPK14	-0.02	0.04	-10000	0	-0.48	3	3
FOXO1	0.028	0.005	-10000	0	-10000	0	0
T-DHT/AR	-0.14	0.1	-10000	0	-0.53	7	7
MAP2K6	0	0.052	-10000	0	-0.63	3	3
BRM/BAF57	0.04	0.012	-10000	0	-10000	0	0
MAP2K4	0.004	0.02	-10000	0	-10000	0	0
SMARCA2	0.027	0.007	-10000	0	-10000	0	0
PDE9A	-0.12	0.14	-10000	0	-0.79	16	16
NCOA2	0.017	0.08	-10000	0	-0.61	8	8
CEBPA	0.018	0.074	-10000	0	-0.5	10	10
EHMT2	0.028	0.006	-10000	0	-10000	0	0
cell proliferation	-0.12	0.13	0.47	5	-0.46	19	24
NR0B1	-0.012	0.13	-10000	0	-0.51	32	32
EGR1	0.012	0.08	-10000	0	-0.61	8	8
RXRs/9cRA	0.047	0.033	-10000	0	-0.3	3	3
AR/RACK1/Src	-0.04	0.064	-10000	0	-0.45	4	4
AR/GR	-0.024	0.086	-10000	0	-0.42	16	16
GNB2L1	0.022	0.012	-10000	0	-10000	0	0
PKN1	0.029	0.002	-10000	0	-10000	0	0
RCHY1	0.029	0.003	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0.001	-10000	0	-0.015	1	1
MAPK8	-0.018	0.027	-10000	0	-0.47	1	1
T-DHT/AR/TIF2/CARM1	-0.051	0.084	-10000	0	-0.47	11	11
SRC	-0.04	0.039	-10000	0	-0.38	3	3
NR3C1	0.021	0.026	-10000	0	-0.5	1	1
KLK3	-0.019	0.13	-10000	0	-0.67	9	9
APPBP2	-0.003	0.019	-10000	0	-10000	0	0
TRIM24	0.026	0.009	-10000	0	-10000	0	0
T-DHT/AR/TIP60	-0.055	0.067	-10000	0	-0.46	6	6
TMPRSS2	-0.91	0.35	-10000	0	-1	449	449
RXRG	0.021	0.05	-10000	0	-0.54	4	4
mol:9cRA	0	0.001	-10000	0	-10000	0	0
RXRA	0.028	0.005	-10000	0	-10000	0	0
RXRB	0.028	0.006	-10000	0	-10000	0	0
CARM1	0.029	0.003	-10000	0	-10000	0	0
NR2C2	0.019	0.031	-10000	0	-0.61	1	1
KLK2	-0.038	0.096	-10000	0	-0.5	13	13
AR	-0.025	0.071	-10000	0	-0.36	18	18
SENP1	0.028	0.005	-10000	0	-10000	0	0
HSP90AA1	0.027	0.008	-10000	0	-10000	0	0
MDM2	0.028	0.006	-10000	0	-10000	0	0
SRY	0	0.003	0.017	18	-10000	0	18
GATA2	0.014	0.09	-10000	0	-0.58	11	11
MYST2	0	0	-10000	0	-10000	0	0
HOXB13	-0.082	0.21	-10000	0	-0.5	101	101
T-DHT/AR/RACK1/Src	-0.04	0.065	-10000	0	-0.44	4	4
positive regulation of transcription	0.014	0.09	-10000	0	-0.58	11	11
DNAJA1	-0.003	0.019	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.027	0.008	-10000	0	-10000	0	0
NCOA1	0.052	0.031	-10000	0	-10000	0	0
SPDEF	-0.088	0.22	-10000	0	-0.51	109	109
T-DHT/AR/TIF2	-0.035	0.091	-10000	0	-0.48	10	10
T-DHT/AR/Hsp90	-0.053	0.065	-10000	0	-0.45	5	5
GSK3B	0.023	0.007	-10000	0	-10000	0	0
NR2C1	0.028	0.005	-10000	0	-10000	0	0
mol:T-DHT	-0.047	0.044	-10000	0	-0.41	4	4
SIRT1	0.028	0.005	-10000	0	-10000	0	0
ZMIZ2	0.026	0.01	-10000	0	-10000	0	0
POU2F1	-0.074	0.047	-10000	0	-10000	0	0
T-DHT/AR/DAX-1	-0.076	0.095	-10000	0	-0.5	11	11
CREBBP	0.028	0.006	-10000	0	-10000	0	0
SMARCE1	0.028	0.005	-10000	0	-10000	0	0

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.022	0.033	-10000	0	-0.6	1	1
HSPA8	0.029	0.004	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	0.072	0.066	0.32	1	-0.41	2	3
AKT1	0.029	0.011	-10000	0	-10000	0	0
GSC	-0.024	0.14	-10000	0	-0.63	3	3
NKX2-5	-0.005	0.11	-10000	0	-0.5	22	22
muscle cell differentiation	-0.03	0.079	0.45	2	-10000	0	2
SMAD2-3/SMAD4/SP1	0.089	0.082	-10000	0	-10000	0	0
SMAD4	0.038	0.033	-10000	0	-10000	0	0
CBFB	0.028	0.006	-10000	0	-10000	0	0
SAP18	0.028	0.005	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.047	0.039	-10000	0	-0.32	3	3
SMAD3/SMAD4/VDR	0.087	0.058	-10000	0	-10000	0	0
MYC	0.007	0.096	-10000	0	-0.51	17	17
CDKN2B	0.017	0.11	-10000	0	-0.61	1	1
AP1	0.057	0.064	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.048	0.063	-10000	0	-0.41	3	3
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.04	0.038	-10000	0	-10000	0	0
SP3	0.03	0.007	-10000	0	-10000	0	0
CREB1	0.028	0.006	-10000	0	-10000	0	0
FOXH1	-0.014	0.14	-10000	0	-0.51	38	38
SMAD3/SMAD4/GR	0.059	0.053	-10000	0	-10000	0	0
GATA3	-0.28	0.32	-10000	0	-0.61	242	242
SKI/SIN3/HDAC complex/NCoR1	0.039	0.032	-10000	0	-0.32	1	1
MEF2C/TIF2	0.029	0.12	-10000	0	-0.49	8	8
endothelial cell migration	0.044	0.14	0.45	14	-10000	0	14
MAX	0.029	0.013	-10000	0	-10000	0	0
RBBP7	0.029	0.003	-10000	0	-10000	0	0
RBBP4	0.027	0.029	-10000	0	-0.61	1	1
RUNX2	0.013	0.087	-10000	0	-0.5	14	14
RUNX3	-0.21	0.26	-10000	0	-0.51	225	225
RUNX1	-0.008	0.13	-10000	0	-0.5	34	34
CTBP1	0.028	0.004	-10000	0	-10000	0	0
NR3C1	0.023	0.029	-10000	0	-0.51	1	1
VDR	0.024	0.049	-10000	0	-0.61	3	3
CDKN1A	0.044	0.077	-10000	0	-10000	0	0
KAT2B	0.019	0.031	-10000	0	-0.61	1	1
SMAD2/SMAD2/SMAD4/FOXH1	0.04	0.11	-10000	0	-0.4	13	13
DCP1A	0.021	0.013	-10000	0	-10000	0	0
SKI	0.028	0.006	-10000	0	-10000	0	0
SERPINE1	-0.044	0.14	-10000	0	-0.45	14	14
SMAD3/SMAD4/ATF2	0.069	0.048	-10000	0	-0.4	1	1
SMAD3/SMAD4/ATF3	0.067	0.056	-10000	0	-0.41	3	3
SAP30	0.011	0.096	-10000	0	-0.5	17	17
Cbp/p300/PIAS3	0.045	0.039	-10000	0	-0.37	1	1
JUN	0.045	0.061	-10000	0	-10000	0	0
SMAD3/SMAD4/IRF7	0.06	0.081	-10000	0	-0.36	2	2
TFE3	0.028	0.02	-10000	0	-10000	0	0
COL1A2	-0.021	0.13	-10000	0	-0.39	55	55
mesenchymal cell differentiation	-0.06	0.075	0.42	2	-10000	0	2
DLX1	-0.25	0.26	-10000	0	-0.5	263	263
TCF3	0.029	0.003	-10000	0	-10000	0	0
FOS	0.019	0.096	-10000	0	-0.6	12	12
SMAD3/SMAD4/Max	0.074	0.046	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.051	0.026	-10000	0	-0.38	1	1
ZBTB17	0.024	0.039	-10000	0	-0.59	2	2
LAMC1	0.047	0.036	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.071	0.042	-10000	0	-10000	0	0
IRF7	0.01	0.1	-10000	0	-0.5	19	19
ESR1	0.024	0.05	-10000	0	-0.5	4	4
HNF4A	-0.02	0.17	-10000	0	-0.61	38	38
MEF2C	0.032	0.13	0.46	8	-0.48	6	14
SMAD2-3/SMAD4	0.078	0.045	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.05	0.029	-10000	0	-0.37	1	1
IGHV3OR16-13	-0.022	0.063	-10000	0	-0.4	8	8
TGIF2/HDAC complex	0.028	0.006	-10000	0	-10000	0	0
CREBBP	0.026	0.01	-10000	0	-10000	0	0
SKIL	0.027	0.007	-10000	0	-10000	0	0
HDAC1	0.028	0.006	-10000	0	-10000	0	0
HDAC2	0.027	0.008	-10000	0	-10000	0	0
SNIP1	0.028	0.006	-10000	0	-10000	0	0
GCN5L2	-0.001	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.076	0.048	-10000	0	-10000	0	0
MSG1/HSC70	0.041	0.026	-10000	0	-0.36	2	2
SMAD2	0.03	0.022	-10000	0	-10000	0	0
SMAD3	0.039	0.032	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.047	0.03	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	-0.018	0.068	0.21	1	-0.45	4	5
NCOR1	0.028	0.005	-10000	0	-10000	0	0
NCOA2	0.017	0.08	-10000	0	-0.61	8	8
NCOA1	0.028	0.005	-10000	0	-10000	0	0
MYOD/E2A	0.015	0.093	-10000	0	-0.36	29	29
SMAD2-3/SMAD4/SP1/MIZ-1	0.096	0.086	-10000	0	-10000	0	0
IFNB1	0.027	0.068	-10000	0	-10000	0	0
SMAD3/SMAD4/MEF2C	0.051	0.12	-10000	0	-0.45	6	6
CITED1	0.026	0.034	-10000	0	-0.5	2	2
SMAD2-3/SMAD4/ARC105	0.092	0.044	-10000	0	-10000	0	0
RBL1	0.028	0.006	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.05	0.039	-10000	0	-10000	0	0
RUNX1-3/PEBPB2	-0.12	0.19	-10000	0	-0.32	237	237
SMAD7	0.072	0.063	-10000	0	-10000	0	0
MYC/MIZ-1	0.02	0.078	-10000	0	-0.37	19	19
SMAD3/SMAD4	0.015	0.08	-10000	0	-0.42	1	1
IL10	-0.15	0.22	-10000	0	-0.76	17	17
PIASy/HDAC complex	0.03	0.008	-10000	0	-10000	0	0
PIAS3	0.027	0.007	-10000	0	-10000	0	0
CDK2	0.027	0.009	-10000	0	-10000	0	0
IL5	-0.12	0.18	-10000	0	-0.56	12	12
CDK4	0.026	0.011	-10000	0	-10000	0	0
PIAS4	0.03	0.008	-10000	0	-10000	0	0
ATF3	0.023	0.051	-10000	0	-0.53	4	4
SMAD3/SMAD4/SP1	0.065	0.08	-10000	0	-10000	0	0
FOXG1	-0.008	0.098	-10000	0	-0.5	18	18
FOXO3	0.021	0.011	-10000	0	-10000	0	0
FOXO1	0.022	0.01	-10000	0	-10000	0	0
FOXO4	0.023	0.01	-10000	0	-10000	0	0
heart looping	0.032	0.13	0.46	8	-0.48	6	14
CEBPB	0.02	0.067	-10000	0	-0.5	8	8
SMAD3/SMAD4/DLX1	-0.13	0.19	-10000	0	-0.37	26	26
MYOD1	-0.008	0.12	-10000	0	-0.5	29	29
SMAD3/SMAD4/HNF4	0.036	0.13	-10000	0	-0.4	38	38
SMAD3/SMAD4/GATA3	-0.15	0.24	-10000	0	-0.49	41	41
SnoN/SIN3/HDAC complex/NCoR1	0.027	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.078	0.18	-10000	0	-0.52	14	14
SMAD3/SMAD4/SP1-3	0.081	0.078	-10000	0	-10000	0	0
MED15	0.028	0.004	-10000	0	-10000	0	0
SP1	0.022	0.045	-10000	0	-10000	0	0
SIN3B	0.029	0.003	-10000	0	-10000	0	0
SIN3A	0.029	0.003	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.027	0.12	-10000	0	-0.44	14	14
ITGB5	0.052	0.073	0.42	2	-10000	0	2
TGIF/SIN3/HDAC complex/CtBP	0.036	0.047	-10000	0	-0.45	3	3
SMAD3/SMAD4/AR	0.053	0.11	-10000	0	-0.4	23	23
AR	-0.001	0.13	-10000	0	-0.6	24	24
negative regulation of cell growth	0.05	0.04	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	0.047	0.097	-10000	0	-0.4	6	6
E2F5	0.026	0.029	-10000	0	-0.61	1	1
E2F4	0.028	0.006	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.041	0.11	-10000	0	-0.39	6	6
SMAD2-3/SMAD4/FOXO1-3a-4	0.048	0.031	-10000	0	-10000	0	0
TFDP1	0.028	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.076	0.068	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX2	0.06	0.075	-10000	0	-0.42	2	2
TGIF2	0.028	0.006	-10000	0	-10000	0	0
TGIF1	0.028	0.005	-10000	0	-10000	0	0
ATF2	0.026	0.029	-10000	0	-0.61	1	1

PLK2 and PLK4 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.011	0.09	-9999	-0.5	15	15
PLK4	0.025	0.041	-9999	-0.5	3	3
regulation of centriole replication	0.006	0.072	-9999	-0.36	18	18

Aurora A 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
Aurora A/GADD45A	0.033	0.038	-10000	0	-10000	0	0
BIRC5	-0.13	0.24	-10000	0	-0.5	148	148
NFKBIA	0.02	0.023	0.25	1	-10000	0	1
CPEB1	-0.097	0.25	-10000	0	-0.6	101	101
AKT1	0.019	0.021	-10000	0	-10000	0	0
NDEL1	0.028	0.005	-10000	0	-10000	0	0
Aurora A/BRCA1	0.028	0.033	-10000	0	-10000	0	0
NDEL1/TACC3	0.044	0.048	-10000	0	-0.38	3	3
GADD45A	0.028	0.006	-10000	0	-10000	0	0
GSK3B	0.029	0.011	-10000	0	-10000	0	0
PAK1/Aurora A	0.035	0.04	-10000	0	-10000	0	0
MDM2	0.028	0.005	-10000	0	-10000	0	0
JUB	0	0	-10000	0	-10000	0	0
TPX2	-0.059	0.16	-10000	0	-0.36	108	108
TP53	0.029	0.024	-10000	0	-0.31	1	1
DLG7	0.017	0.021	-10000	0	-10000	0	0
AURKAIP1	0.024	0.047	-10000	0	-0.57	3	3
ARHGEF7	0.028	0.004	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.046	0.05	-10000	0	-0.4	3	3
G2/M transition of mitotic cell cycle	0.027	0.033	-10000	0	-10000	0	0
AURKA	0.027	0.028	-10000	0	-10000	0	0
AURKB	-0.049	0.074	-10000	0	-0.21	14	14
CDC25B	0.025	0.027	-10000	0	-0.27	1	1
G2/M transition checkpoint	0.01	0.028	-10000	0	-10000	0	0
mRNA polyadenylation	-0.044	0.15	-10000	0	-0.34	99	99
Aurora A/CPEB	-0.045	0.15	-10000	0	-0.34	99	99
Aurora A/TACC1/TRAP/chTOG	0.058	0.043	-10000	0	-10000	0	0
BRCA1	0.028	0.004	-10000	0	-10000	0	0
centrosome duplication	0.035	0.039	-10000	0	-10000	0	0
regulation of centrosome cycle	0.042	0.047	-10000	0	-0.37	3	3
spindle assembly	0.057	0.042	-10000	0	-10000	0	0
TDRD7	0.028	0.006	-10000	0	-10000	0	0
Aurora A/RasGAP/Survivin	-0.025	0.13	-10000	0	-0.35	13	13
CENPA	-0.035	0.066	-10000	0	-0.21	13	13
Aurora A/PP2A	0.034	0.037	-10000	0	-10000	0	0
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	0.025	0.029	0.19	1	-10000	0	1
negative regulation of DNA binding	0.029	0.024	-10000	0	-0.31	1	1
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.041	0.008	-10000	0	-10000	0	0
RASA1	0.024	0.03	-10000	0	-0.61	1	1
Ajuba/Aurora A	0.011	0.028	-10000	0	-10000	0	0
mitotic prometaphase	0.018	0.023	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.027	0.028	-10000	0	-10000	0	0
TACC1	0.026	0.008	-10000	0	-10000	0	0
TACC3	0.024	0.047	-10000	0	-0.5	4	4
Aurora A/Antizyme1	0.045	0.049	-10000	0	-0.34	2	2
Aurora A/RasGAP	0.031	0.041	-10000	0	-0.38	1	1
OAZ1	0.027	0.024	-10000	0	-0.5	1	1
RAN	0.028	0.005	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	0.031	0.009	-10000	0	-10000	0	0
GIT1	0.028	0.004	-10000	0	-10000	0	0
GIT1/beta-PIX/PAK1	0.056	0.012	-10000	0	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.059	0.16	-10000	0	-0.36	108	108
PPP2R5D	0.028	0.006	-10000	0	-10000	0	0
Aurora A/TPX2	-0.037	0.12	-10000	0	-0.37	9	9
PAK1	0.029	0.003	-10000	0	-10000	0	0
CKAP5	0.029	0.003	-10000	0	-10000	0	0

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	0.022	0.048	-10000	0	-10000	0	0
CRKL	0.028	0.004	-10000	0	-10000	0	0
Rac1/GDP	0.019	0.007	-10000	0	-10000	0	0
DOCK1	0.026	0.029	-10000	0	-0.61	1	1
ITGA4	0.012	0.09	-10000	0	-0.5	15	15
alpha4/beta7 Integrin/MAdCAM1	0.032	0.08	-10000	0	-0.31	3	3
EPO	-0.14	0.25	-10000	0	-0.5	163	163
alpha4/beta7 Integrin	0.028	0.069	-10000	0	-0.36	15	15
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.028	0.005	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.028	0.069	-10000	0	-0.36	15	15
EPO/EPOR (dimer)	-0.092	0.19	-10000	0	-0.36	163	163
lamellipodium assembly	0.019	0.091	0.31	1	-0.52	7	8
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
PI3K	0.036	0.034	-10000	0	-0.45	2	2
ARF6	0.027	0.008	-10000	0	-10000	0	0
JAK2	-0.033	0.099	-10000	0	-0.33	9	9
PXN	0.028	0.005	-10000	0	-10000	0	0
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
MADCAM1	0.015	0.079	-10000	0	-0.51	11	11
cell adhesion	0.03	0.078	-10000	0	-0.31	3	3
CRKL/CBL	0.041	0.023	-10000	0	-0.45	1	1
ITGB1	0.028	0.004	-10000	0	-10000	0	0
SRC	0.014	0.072	-10000	0	-0.33	1	1
ITGB7	0.028	0.005	-10000	0	-10000	0	0
RAC1	0.026	0.009	-10000	0	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.035	0.081	-10000	0	-0.31	25	25
p130Cas/Crk/Dock1	0.035	0.073	-10000	0	-0.53	1	1
VCAM1	0.016	0.079	-10000	0	-0.47	13	13
RHOA	0.021	0.013	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.057	0.062	-10000	0	-10000	0	0
BCAR1	0.006	0.07	-10000	0	-0.58	1	1
EPOR	0.029	0.003	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.027	0.028	-10000	0	-0.61	1	1
GIT1	0.028	0.004	-10000	0	-10000	0	0
Rac1/GTP	0.018	0.093	0.31	1	-0.54	7	8

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.002	0.082	0.53	1	-10000	0	1
GNAI2	0.02	0.013	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.02	0.12	-10000	0	-0.31	78	78
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.023	0.05	-10000	0	-0.53	4	4
RhoA/GTP	-0.001	0.084	-10000	0	-0.54	1	1
negative regulation of cAMP metabolic process	-0.011	0.088	-10000	0	-0.31	18	18
GNAZ	0.025	0.049	-10000	0	-0.61	3	3
GNAI3	0.028	0.005	-10000	0	-10000	0	0
GNA12	0.026	0.009	-10000	0	-10000	0	0
S1PR5	-0.062	0.2	-10000	0	-0.5	87	87
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.011	0.088	-10000	0	-0.31	18	18
RhoA/GDP	0.015	0.01	-10000	0	-10000	0	0
RHOA	0.021	0.013	-10000	0	-10000	0	0
GNAI1	0.024	0.03	-10000	0	-0.61	1	1

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.052	0.053	-10000	0	-0.33	3	3
ER alpha/Gai/GDP/Gbeta gamma	-0.035	0.17	-10000	0	-0.53	36	36
AKT1	-0.034	0.22	-10000	0	-0.73	44	44
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.034	0.23	-10000	0	-0.75	45	45
mol:Ca2+	-0.015	0.11	-10000	0	-0.41	17	17
IGF1R	0.029	0.003	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	0.03	0.053	-10000	0	-0.43	6	6
SHC1	0.027	0.006	-10000	0	-10000	0	0
apoptosis	0.031	0.21	0.68	46	-10000	0	46
RhoA/GTP	0.017	0.028	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	0.001	0.14	-10000	0	-0.57	12	12
regulation of stress fiber formation	-0.029	0.053	-10000	0	-0.36	4	4
E2/ERA-ERB (dimer)	0.026	0.052	-10000	0	-0.34	9	9
KRAS	0.028	0.005	-10000	0	-10000	0	0
G13/GTP	0.031	0.031	-10000	0	-0.33	3	3
pseudopodium formation	0.029	0.053	0.36	4	-10000	0	4
E2/ER alpha (dimer)/PELP1	0.033	0.034	-10000	0	-0.36	3	3
GRB2	0.028	0.005	-10000	0	-10000	0	0
GNG2	0.027	0.008	-10000	0	-10000	0	0
GNAO1	0.023	0.05	-10000	0	-0.53	4	4
HRAS	0.028	0.024	-10000	0	-0.5	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.009	0.17	0.31	5	-0.53	41	46
E2/ER beta (dimer)	0.015	0.045	-10000	0	-0.35	7	7
mol:GDP	0.019	0.047	-10000	0	-0.4	3	3
mol:NADP	-0.009	0.17	0.31	5	-0.53	41	46
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
mol:IP3	-0.015	0.11	-10000	0	-0.43	16	16
IGF-1R heterotetramer	0.029	0.003	-10000	0	-10000	0	0
PLCB1	0.014	0.081	-10000	0	-0.47	9	9
PLCB2	-0.011	0.11	-10000	0	-0.42	15	15
IGF1	0.023	0.053	-10000	0	-0.5	5	5
mol:L-citrulline	-0.009	0.17	0.31	5	-0.53	41	46
RHOA	0.021	0.013	-10000	0	-10000	0	0
Gai/GDP	-0.11	0.26	-10000	0	-0.54	122	122
JNK cascade	0.015	0.044	-10000	0	-0.35	7	7
BCAR1	0.027	0.029	-10000	0	-0.61	1	1
ESR2	0.02	0.061	-10000	0	-0.49	7	7
GNAQ	0.028	0.006	-10000	0	-10000	0	0
ESR1	0.022	0.049	-10000	0	-0.51	4	4
Gq family/GDP/Gbeta gamma	0.018	0.11	-10000	0	-0.71	8	8
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.026	0.14	-10000	0	-0.92	9	9
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	0.001	0.14	-10000	0	-0.59	11	11
GNAZ	0.025	0.049	-10000	0	-0.61	3	3
E2/ER alpha (dimer)	0.017	0.036	-10000	0	-0.37	4	4
STRN	0.023	0.057	-10000	0	-0.61	4	4
GNAL	0.028	0.005	-10000	0	-10000	0	0
PELP1	0.028	0.005	-10000	0	-10000	0	0
MAPK11	0.013	0.04	-10000	0	-0.32	7	7
GNAI2	0.02	0.013	-10000	0	-10000	0	0
GNAI3	0.028	0.005	-10000	0	-10000	0	0
GNAI1	0.024	0.03	-10000	0	-0.61	1	1
HBEGF	-0.076	0.17	0.38	9	-0.54	28	37
cAMP biosynthetic process	0.023	0.042	-10000	0	-0.27	9	9
SRC	-0.029	0.16	-10000	0	-0.51	34	34
PI3K	0.036	0.034	-10000	0	-0.45	2	2
GNB1	0.028	0.006	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	0.039	0.061	-10000	0	-0.38	2	2
SOS1	0.028	0.005	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.039	0.097	-10000	0	-0.47	13	13
Gs family/GTP	0.03	0.045	-10000	0	-0.27	9	9
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.051	0.021	-10000	0	-0.28	1	1
vasodilation	-0.007	0.17	0.31	5	-0.5	41	46
mol:DAG	-0.015	0.11	-10000	0	-0.43	16	16
Gs family/GDP/Gbeta gamma	0.019	0.053	-10000	0	-0.36	2	2
MSN	0.029	0.055	0.37	4	-10000	0	4
Gq family/GTP	0.021	0.072	-10000	0	-0.46	8	8
mol:PI-3-4-5-P3	-0.031	0.22	-10000	0	-0.71	46	46
NRAS	0.028	0.005	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.007	0.17	0.5	41	-0.31	5	46
GRB2/SOS1	0.041	0.009	-10000	0	-10000	0	0
RhoA/GDP	0.019	0.06	-10000	0	-0.37	3	3
NOS3	-0.011	0.18	0.33	4	-0.56	41	45
GNA11	0.025	0.049	-10000	0	-0.61	3	3
MAPKKK cascade	0	0.18	0.38	4	-0.55	43	47
E2/ER alpha (dimer)/PELP1/Src	-0.003	0.15	-10000	0	-0.52	20	20
ruffle organization	0.029	0.053	0.36	4	-10000	0	4
ROCK2	0.035	0.057	0.38	4	-10000	0	4
GNA14	0.02	0.069	-10000	0	-0.61	6	6
GNA15	0.013	0.09	-10000	0	-0.5	15	15
GNA13	0.028	0.005	-10000	0	-10000	0	0
MMP9	-0.13	0.18	0.38	7	-0.54	37	44
MMP2	-0.025	0.16	0.33	2	-0.58	20	22

S1P3 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.022	0.012	-9999	-10000	0	0
mol:S1P	0.001	0	-9999	-10000	0	0
S1P1/S1P/Gi	0.007	0.049	-9999	-0.27	4	4
GNAO1	0.025	0.05	-9999	-0.53	4	4
S1P/S1P3/G12/G13	0.049	0.021	-9999	-10000	0	0
AKT1	0.024	0.04	-9999	-0.38	1	1
AKT3	-0.009	0.082	-9999	-0.5	3	3
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.022	0.012	-9999	-10000	0	0
GNAI2	0.022	0.014	-9999	-10000	0	0
GNAI3	0.029	0.005	-9999	-10000	0	0
GNAI1	0.026	0.03	-9999	-0.61	1	1
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.029	0.006	-9999	-10000	0	0
S1PR2	0.029	0.003	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.029	0.039	-9999	-0.28	2	2
MAPK3	0.026	0.036	-9999	-10000	0	0
MAPK1	0.027	0.037	-9999	-10000	0	0
JAK2	-0.022	0.086	-9999	-0.46	3	3
CXCR4	-0.066	0.13	-9999	-0.35	5	5
FLT1	0.025	0.053	-9999	-0.5	5	5
RhoA/GDP	0.015	0.01	-9999	-10000	0	0
Rac1/GDP	0.019	0.007	-9999	-10000	0	0
SRC	0.026	0.036	-9999	-10000	0	0
S1P/S1P3/Gi	0.029	0.04	-9999	-0.29	2	2
RAC1	0.026	0.009	-9999	-10000	0	0
RhoA/GTP	0.034	0.048	-9999	-10000	0	0
VEGFA	-0.21	0.26	-9999	-0.5	228	228
S1P/S1P2/Gi	0.027	0.041	-9999	-0.29	2	2
VEGFR1 homodimer/VEGFA homodimer	-0.14	0.21	-9999	-0.36	228	228
RHOA	0.021	0.013	-9999	-10000	0	0
S1P/S1P3/Gq	0.025	0.051	-9999	-0.29	9	9
GNAQ	0.028	0.006	-9999	-10000	0	0
GNAZ	0.026	0.049	-9999	-0.61	3	3
G12/G13	0.037	0.015	-9999	-10000	0	0
GNA14	0.02	0.069	-9999	-0.61	6	6
GNA15	0.013	0.09	-9999	-0.5	15	15
GNA12	0.026	0.009	-9999	-10000	0	0
GNA13	0.028	0.005	-9999	-10000	0	0
GNA11	0.025	0.049	-9999	-0.61	3	3
Rac1/GTP	0.023	0.054	-9999	-10000	0	0

ErbB4 signaling events

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
ErbB4/ErbB4/HBEGF/HBEGF	-0.078	0.082	-10000	0	-0.37	1	1
epithelial cell differentiation	-0.05	0.1	-10000	0	-0.45	3	3
ITCH	0.061	0.02	-10000	0	-10000	0	0
WWP1	-0.092	0.064	-10000	0	-10000	0	0
FYN	0.027	0.008	-10000	0	-10000	0	0
EGFR	0.019	0.06	-10000	0	-0.52	6	6
PRL	0.021	0.007	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.051	0.078	0.37	2	-0.51	1	3
PTPRZ1	-0.046	0.2	-10000	0	-0.6	56	56
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.061	0.077	-10000	0	-0.44	4	4
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.08	0.08	-10000	0	-0.45	10	10
ADAM17	0.062	0.019	-10000	0	-10000	0	0
ErbB4/ErbB4	-0.12	0.083	-10000	0	-0.42	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.11	0.086	-10000	0	-0.41	9	9
NCOR1	0.028	0.005	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.071	0.078	-10000	0	-0.44	8	8
GRIN2B	-0.069	0.074	-10000	0	-0.42	8	8
ErbB4/ErbB2/betacellulin	-0.11	0.13	-10000	0	-0.43	59	59
STAT1	0.026	0.024	-10000	0	-0.5	1	1
HBEGF	0.022	0.012	-10000	0	-10000	0	0
PRLR	-0.048	0.2	-10000	0	-0.61	59	59
E4ICDs/ETO2	-0.1	0.078	-10000	0	-0.41	3	3
axon guidance	-0.046	0.08	-10000	0	-10000	0	0
NEDD4	0.06	0.045	-10000	0	-0.6	2	2
Prolactin receptor/Prolactin receptor/Prolactin	-0.024	0.16	-10000	0	-0.46	59	59
CBFA2T3	0.026	0.034	-10000	0	-0.5	2	2
ErbB4/ErbB2/HBEGF	-0.048	0.064	-10000	0	-0.43	1	1
MAPK3	-0.055	0.077	0.44	1	-0.52	1	2
STAT1 (dimer)	-0.1	0.075	-10000	0	-0.37	1	1
MAPK1	-0.055	0.079	0.35	3	-0.52	1	4
JAK2	0.027	0.007	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.077	0.076	-10000	0	-0.44	9	9
NRG1	0.025	0.076	-10000	0	-0.44	12	12
NRG3	0.017	0.076	-10000	0	-0.52	10	10
NRG2	0.012	0.072	-10000	0	-0.52	9	9
NRG4	-0.027	0.18	-10000	0	-0.59	45	45
heart development	-0.046	0.08	-10000	0	-10000	0	0
neural crest cell migration	-0.077	0.075	-10000	0	-0.44	9	9
ERBB2	0.039	0.033	-10000	0	-0.45	2	2
WWOX/E4ICDs	-0.1	0.077	-10000	0	-0.37	2	2
SHC1	0.027	0.006	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.12	0.12	-10000	0	-0.45	35	35
apoptosis	0.089	0.076	0.34	11	-10000	0	11
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.083	0.087	-10000	0	-0.4	5	5
ErbB4/ErbB2/epiregulin	-0.082	0.087	-10000	0	-0.36	21	21
ErbB4/ErbB4/betacellulin/betacellulin	-0.16	0.15	-10000	0	-0.48	69	69
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.093	0.12	-10000	0	-0.44	32	32
MDM2	-0.1	0.071	-10000	0	-0.37	1	1
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.054	0.068	-10000	0	-0.4	10	10
STAT5A	-0.041	0.075	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.073	0.082	-10000	0	-0.42	12	12
DLG4	0.028	0.005	-10000	0	-10000	0	0
GRB2/SHC	0.04	0.011	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.096	0.068	-10000	0	-0.35	1	1
STAT5A (dimer)	-0.049	0.11	-10000	0	-0.48	3	3
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.039	0.084	0.35	1	-10000	0	1
LRIG1	0.022	0.012	-10000	0	-10000	0	0
EREG	-0.005	0.13	-10000	0	-0.51	31	31
BTC	-0.063	0.22	-10000	0	-0.6	74	74
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.047	0.079	-10000	0	-10000	0	0
ERBB4	-0.12	0.083	-10000	0	-0.42	1	1
STAT5B	0.028	0.004	-10000	0	-10000	0	0
YAP1	-0.021	0.039	-10000	0	-0.53	2	2
GRB2	0.028	0.005	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.096	0.11	-10000	0	-0.42	34	34
glial cell differentiation	0.096	0.067	0.34	1	-10000	0	1
WWOX	0.026	0.024	-10000	0	-0.5	1	1
cell proliferation	-0.079	0.14	0.34	1	-0.55	16	17

FAS signaling pathway (CD95)

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
SPTAN1	0.006	0.022	-10000	0	-10000	0	0
RFC1	0.005	0.02	-10000	0	-10000	0	0
PRKDC	0.008	0.033	0.31	1	-10000	0	1
RIPK1	0.028	0.006	-10000	0	-10000	0	0
CASP7	-0.009	0.11	-10000	0	-0.63	12	12
FASLG/FAS/FADD/FAF1	-0.059	0.092	0.23	6	-0.27	3	9
MAP2K4	-0.043	0.14	0.31	5	-0.55	18	23
mol:ceramide	-0.066	0.11	-10000	0	-0.34	10	10
GSN	0.006	0.022	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 8	-0.068	0.099	-10000	0	-0.39	4	4
FAS	0.026	0.011	-10000	0	-10000	0	0
BID	-0.001	0.033	-10000	0	-10000	0	0
MAP3K1	-0.013	0.12	0.31	5	-0.5	16	21
MAP3K7	0.027	0.007	-10000	0	-10000	0	0
RB1	0.006	0.026	-10000	0	-10000	0	0
CFLAR	0.028	0.007	-10000	0	-10000	0	0
HGF/MET	0.029	0.097	-10000	0	-0.38	25	25
ARHGDIB	0.01	0.035	-10000	0	-10000	0	0
FADD	0.026	0.011	-10000	0	-10000	0	0
actin filament polymerization	-0.006	0.022	-10000	0	-10000	0	0
NFKB1	-0.023	0.089	-10000	0	-0.59	7	7
MAPK8	-0.05	0.16	0.34	6	-0.52	31	37
DFFA	0.005	0.02	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.005	0.02	-10000	0	-10000	0	0
FAS/FADD/MET	0.047	0.031	-10000	0	-0.3	2	2
CFLAR/RIP1	0.041	0.012	-10000	0	-10000	0	0
FAIM3	-0.009	0.13	-10000	0	-0.5	35	35
FAF1	0.025	0.014	-10000	0	-10000	0	0
PARP1	0.005	0.02	-10000	0	-10000	0	0
DFFB	0.005	0.02	-10000	0	-10000	0	0
CHUK	-0.017	0.076	-10000	0	-0.55	5	5
FASLG	-0.24	0.26	-10000	0	-0.5	255	255
FAS/FADD	0.038	0.017	-10000	0	-10000	0	0
HGF	0.003	0.11	-10000	0	-0.54	20	20
LMNA	0.004	0.029	0.27	1	-10000	0	1
CASP6	0.005	0.02	-10000	0	-10000	0	0
CASP10	0.026	0.011	-10000	0	-10000	0	0
CASP3	0.004	0.026	-10000	0	-10000	0	0
PTPN13	0.017	0.084	-10000	0	-0.61	9	9
CASP8	0.001	0.059	0.22	35	-10000	0	35
IL6	-0.076	0.29	-10000	0	-1.1	32	32
MET	0.024	0.034	-10000	0	-0.5	2	2
ICAD/CAD	0.007	0.019	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 10	-0.067	0.11	-10000	0	-0.35	10	10
activation of caspase activity by cytochrome c	-0.001	0.033	-10000	0	-10000	0	0
PAK2	0.009	0.036	-10000	0	-10000	0	0
BCL2	0.028	0.005	-10000	0	-10000	0	0

TCGA08_rtk_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
PDGFRA	-0.22	0.31	-10000	0	-0.61	196	196
HRAS	0.028	0.024	-10000	0	-0.5	1	1
EGFR	0.019	0.06	-10000	0	-0.52	6	6
AKT	0.028	0.089	0.28	24	-10000	0	24
FOXO3	0.027	0.008	-10000	0	-10000	0	0
AKT1	0.027	0.008	-10000	0	-10000	0	0
FOXO1	0.028	0.005	-10000	0	-10000	0	0
AKT3	0.028	0.006	-10000	0	-10000	0	0
FOXO4	0.029	0.001	-10000	0	-10000	0	0
MET	0.024	0.034	-10000	0	-0.5	2	2
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
PIK3CB	0.027	0.007	-10000	0	-10000	0	0
NRAS	0.028	0.005	-10000	0	-10000	0	0
PIK3CG	0.023	0.041	-10000	0	-0.5	3	3
PIK3R3	0.028	0.006	-10000	0	-10000	0	0
PIK3R2	0.029	0.003	-10000	0	-10000	0	0
NF1	0.028	0.004	-10000	0	-10000	0	0
RAS	-0.029	0.081	0.19	2	-0.25	3	5
ERBB2	0.026	0.04	-10000	0	-0.61	2	2
proliferation/survival/translation	-0.041	0.061	0.26	8	-0.21	5	13
PI3K	-0.002	0.1	0.3	24	-0.25	6	30
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
KRAS	0.028	0.005	-10000	0	-10000	0	0
FOXO	0.053	0.072	0.27	23	-10000	0	23
AKT2	0.029	0.003	-10000	0	-10000	0	0
PTEN	0.028	0.006	-10000	0	-10000	0	0

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.017	0.08	-10000	0	-0.48	5	5
BAG4	0.025	0.029	-10000	0	-0.61	1	1
BAD	0.018	0.054	0.34	6	-0.24	3	9
NFKBIA	0.027	0.007	-10000	0	-10000	0	0
BIRC3	-0.054	0.19	-10000	0	-0.5	79	79
BAX	0.02	0.048	0.25	11	-0.19	1	12
EnzymeConsortium:3.1.4.12	0.01	0.031	0.12	12	-0.1	5	17
IKBKB	0.023	0.081	0.33	3	-0.47	4	7
MAP2K2	0.025	0.059	0.29	11	-0.27	1	12
MAP2K1	0.026	0.061	0.3	12	-10000	0	12
SMPD1	0.015	0.034	0.21	6	-0.15	2	8
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.024	0.087	0.37	1	-0.49	5	6
MAP2K4	0.034	0.072	0.22	45	-10000	0	45
protein ubiquitination	0.028	0.097	0.38	9	-0.46	5	14
EnzymeConsortium:2.7.1.37	0.032	0.069	0.34	11	-10000	0	11
response to UV	0	0.001	0.004	20	-0.003	1	21
RAF1	0.016	0.056	0.28	11	-10000	0	11
CRADD	0.028	0.005	-10000	0	-10000	0	0
mol:ceramide	0.017	0.045	0.2	10	-0.17	3	13
I-kappa-B-alpha/RELA/p50/ubiquitin	0.036	0.01	-10000	0	-10000	0	0
MADD	0.029	0.003	-10000	0	-10000	0	0
MAP3K1	0.032	0.07	0.22	43	-0.2	1	44
TRADD	0.028	0.006	-10000	0	-10000	0	0
RELA/p50	0.029	0.003	-10000	0	-10000	0	0
MAPK3	0.029	0.059	0.28	13	-10000	0	13
MAPK1	0.029	0.059	0.29	12	-10000	0	12
p50/RELA/I-kappa-B-alpha	0.04	0.011	-10000	0	-10000	0	0
FADD	0.013	0.081	0.37	1	-0.48	5	6
KSR1	0.02	0.053	0.26	10	-0.21	5	15
MAPK8	0.034	0.074	0.31	15	-0.27	1	16
TRAF2	0.028	0.006	-10000	0	-10000	0	0
response to radiation	0	0.001	0.004	8	-10000	0	8
CHUK	0.024	0.081	0.29	3	-0.51	3	6
TNF R/SODD	0.037	0.026	-10000	0	-0.45	1	1
TNF	0.019	0.073	-10000	0	-0.56	8	8
CYCS	0.024	0.059	0.25	15	-0.19	1	16
IKBKG	0.024	0.085	0.3	4	-0.51	3	7
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.013	0.085	-10000	0	-0.5	5	5
RELA	0.029	0.003	-10000	0	-10000	0	0
RIPK1	0.028	0.006	-10000	0	-10000	0	0
AIFM1	0.018	0.051	0.24	12	-0.19	1	13
TNF/TNF R/SODD	0.044	0.057	-10000	0	-0.35	9	9
TNFRSF1A	0.028	0.006	-10000	0	-10000	0	0
response to heat	0	0.001	0.004	8	-10000	0	8
CASP8	0.022	0.098	-10000	0	-0.61	11	11
NSMAF	0.016	0.084	0.32	2	-0.47	5	7
response to hydrogen peroxide	0	0.001	0.004	20	-0.003	1	21
BCL2	0.028	0.005	-10000	0	-10000	0	0

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	0.037	0.039	-10000	0	-0.45	3	3
AKT1	-0.007	0.12	0.44	7	-0.52	4	11
PTK2B	-0.08	0.14	0.35	2	-0.83	1	3
VEGFR2 homodimer/Frs2	0.04	0.041	-10000	0	-0.56	2	2
CAV1	-0.006	0.12	-10000	0	-0.5	30	30
CALM1	0.027	0.008	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.084	0.16	-10000	0	-0.64	2	2
endothelial cell proliferation	0.012	0.14	0.47	20	-0.45	2	22
mol:Ca2+	-0.082	0.14	-10000	0	-0.69	1	1
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.065	0.15	-10000	0	-0.73	1	1
RP11-342D11.1	-0.088	0.14	-10000	0	-0.84	1	1
CDH5	0.027	0.024	-10000	0	-0.5	1	1
VEGFA homodimer	-0.089	0.16	-10000	0	-0.34	4	4
SHC1	0.027	0.006	-10000	0	-10000	0	0
SHC2	0.023	0.057	-10000	0	-0.55	5	5
HRAS/GDP	-0.061	0.13	-10000	0	-0.55	2	2
SH2D2A	-0.14	0.25	-10000	0	-0.5	160	160
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.012	0.12	-10000	0	-0.56	1	1
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.18	0.2	-10000	0	-0.52	64	64
VEGFR1 homodimer	0.023	0.053	-10000	0	-0.5	5	5
SHC/GRB2/SOS1	-0.052	0.15	-10000	0	-0.67	1	1
GRB10	-0.076	0.14	-10000	0	-0.69	1	1
PTPN11	0.028	0.005	-10000	0	-10000	0	0
GRB2	0.028	0.005	-10000	0	-10000	0	0
PAK1	0.029	0.003	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.063	0.15	-10000	0	-0.67	2	2
HRAS	0.028	0.024	-10000	0	-0.5	1	1
VEGF/Rho/ROCK1/Integrin Complex	-0.04	0.1	-10000	0	-0.37	14	14
HIF1A	0.024	0.041	-10000	0	-0.61	2	2
FRS2	0.028	0.005	-10000	0	-10000	0	0
oxygen and reactive oxygen species metabolic process	-0.065	0.15	-10000	0	-0.72	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.021	0.013	-10000	0	-10000	0	0
Nck/Pak	0.039	0.024	-10000	0	-0.45	1	1
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.086	0.16	-10000	0	-0.93	1	1
mol:GDP	-0.059	0.14	-10000	0	-0.64	1	1
mol:NADP	-0.01	0.11	0.46	5	-0.46	1	6
eNOS/Hsp90	-0.005	0.1	0.36	2	-0.42	1	3
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
mol:IP3	-0.082	0.14	-10000	0	-0.7	1	1
HIF1A/ARNT	0.036	0.034	-10000	0	-0.45	2	2
SHB	0.028	0.006	-10000	0	-10000	0	0
VEGFA	-0.21	0.26	-10000	0	-0.5	228	228
VEGFC	0.027	0.024	-10000	0	-0.5	1	1
FAK1/Vinculin	-0.051	0.13	0.45	2	-0.54	4	6
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.021	0.013	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.069	0.16	-10000	0	-0.89	1	1
PTPN6	0.028	0.006	-10000	0	-10000	0	0
EPAS1	0.035	0.033	-10000	0	-0.47	2	2
mol:L-citrulline	-0.01	0.11	0.46	5	-0.46	1	6
ITGAV	0.027	0.006	-10000	0	-10000	0	0
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.069	0.16	-10000	0	-0.89	1	1
VEGFR2 homodimer/VEGFA homodimer	-0.081	0.16	-10000	0	-0.92	1	1
VEGFR2/3 heterodimer	0.03	0.038	-10000	0	-0.47	2	2
VEGFB	0.029	0.003	-10000	0	-10000	0	0
MAPK11	-0.078	0.13	0.34	1	-0.62	2	3
VEGFR2 homodimer	0.028	0.044	-10000	0	-0.63	2	2
FLT1	0.023	0.053	-10000	0	-0.5	5	5
NEDD4	0.028	0.04	-10000	0	-0.61	2	2
MAPK3	-0.078	0.13	0.32	3	-0.66	1	4
MAPK1	-0.076	0.13	0.32	3	-0.6	1	4
VEGFA145/NRP2	-0.14	0.2	-10000	0	-0.36	225	225
VEGFR1/2 heterodimer	0.037	0.052	-10000	0	-0.55	2	2
KDR	0.028	0.044	-10000	0	-0.63	2	2
VEGFA165/NRP1/VEGFR2 homodimer	-0.068	0.16	-10000	0	-0.77	2	2
SRC	0.028	0.006	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	-0.067	0.14	0.38	8	-0.64	1	9
PI3K	-0.037	0.12	-10000	0	-0.52	3	3
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.086	0.16	-10000	0	-0.48	3	3
FES	-0.084	0.15	-10000	0	-0.72	2	2
GAB1	-0.043	0.11	-10000	0	-0.74	1	1
VEGFR2 homodimer/VEGFA homodimer/Src	-0.085	0.16	-10000	0	-0.56	2	2
CTNNB1	0.02	0.013	-10000	0	-10000	0	0
SOS1	0.028	0.005	-10000	0	-10000	0	0
ARNT	0.027	0.006	-10000	0	-10000	0	0
eNOS/Caveolin-1	-0.023	0.1	0.32	1	-0.38	1	2
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.083	0.16	-10000	0	-0.64	2	2
PI3K/GAB1	-0.005	0.1	-10000	0	-0.48	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.06	0.16	-10000	0	-0.71	1	1
PRKACA	0.029	0.002	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.041	0.043	-10000	0	-0.53	1	1
HSP90AA1	0.027	0.008	-10000	0	-10000	0	0
CDC42	-0.083	0.15	-10000	0	-0.85	1	1
actin cytoskeleton reorganization	-0.18	0.2	-10000	0	-0.52	64	64
PTK2	-0.06	0.12	-10000	0	-0.6	3	3
EDG1	-0.088	0.14	-10000	0	-0.84	1	1
mol:DAG	-0.082	0.14	-10000	0	-0.7	1	1
CaM/Ca2+	-0.069	0.13	-10000	0	-0.63	1	1
MAP2K3	-0.08	0.13	0.38	1	-0.68	1	2
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.05	0.16	-10000	0	-0.72	1	1
PLCG1	-0.083	0.14	-10000	0	-0.71	1	1
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.07	0.16	-10000	0	-0.73	1	1
IQGAP1	0.029	0.003	-10000	0	-10000	0	0
YES1	0.028	0.004	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.085	0.16	-10000	0	-0.64	2	2
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.085	0.16	-10000	0	-0.64	2	2
cell migration	-0.023	0.12	0.42	3	-0.49	4	7
mol:PI-3-4-5-P3	-0.035	0.11	-10000	0	-0.49	3	3
FYN	0.027	0.008	-10000	0	-10000	0	0
VEGFB/NRP1	-0.074	0.14	-10000	0	-0.79	1	1
mol:NO	-0.01	0.11	0.46	5	-0.46	1	6
PXN	0.028	0.005	-10000	0	-10000	0	0
HRAS/GTP	-0.072	0.12	-10000	0	-0.55	2	2
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.071	0.15	-10000	0	-0.73	1	1
VHL	0.02	0.019	-10000	0	-0.3	1	1
ITGB3	0.024	0.049	-10000	0	-0.61	3	3
NOS3	-0.014	0.12	0.48	5	-0.52	1	6
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.088	0.16	-10000	0	-0.76	2	2
RAC1	0.026	0.009	-10000	0	-10000	0	0
PRKCA	-0.079	0.13	-10000	0	-0.66	1	1
PRKCB	-0.081	0.13	-10000	0	-0.56	2	2
VCL	0.028	0.005	-10000	0	-10000	0	0
VEGFA165/NRP1	-0.083	0.15	-10000	0	-0.86	1	1
VEGFR1/2 heterodimer/VEGFA homodimer	-0.088	0.17	-10000	0	-0.56	6	6
VEGFA165/NRP2	-0.14	0.2	-10000	0	-0.36	225	225
MAPKKK cascade	-0.045	0.14	0.44	1	-0.48	2	3
NRP2	0.02	0.062	-10000	0	-0.5	7	7
VEGFC homodimer	0.027	0.024	-10000	0	-0.5	1	1
NCK1	0.026	0.029	-10000	0	-0.61	1	1
ROCK1	0.028	0.004	-10000	0	-10000	0	0
FAK1/Paxillin	-0.049	0.13	0.4	3	-0.54	4	7
MAP3K13	-0.083	0.14	-10000	0	-0.71	1	1
PDPK1	-0.035	0.1	0.28	1	-0.58	2	3

S1P4 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
mol:S1P	0	0	-10000	0	-10000	0	0
GNAO1	0.023	0.05	-10000	0	-0.53	4	4
CDC42/GTP	0.011	0.064	-10000	0	-0.28	4	4
PLCG1	0.012	0.05	-10000	0	-0.29	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.02	0.013	-10000	0	-10000	0	0
GNAI3	0.028	0.005	-10000	0	-10000	0	0
G12/G13	0.037	0.015	-10000	0	-10000	0	0
cell migration	0.011	0.062	-10000	0	-0.28	4	4
S1PR5	-0.062	0.2	-10000	0	-0.5	87	87
S1PR4	0.001	0.12	-10000	0	-0.5	26	26
MAPK3	0.012	0.05	-10000	0	-0.29	4	4
MAPK1	0.013	0.051	-10000	0	-0.34	1	1
S1P/S1P5/Gi	-0.011	0.088	-10000	0	-0.31	18	18
GNAI1	0.024	0.03	-10000	0	-0.61	1	1
CDC42/GDP	0.02	0.004	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.02	0.12	-10000	0	-0.31	78	78
RHOA	0.015	0.078	0.36	4	-10000	0	4
S1P/S1P4/Gi	0.014	0.054	-10000	0	-0.31	4	4
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	0.025	0.049	-10000	0	-0.61	3	3
S1P/S1P4/G12/G13	0.032	0.072	-10000	0	-0.28	24	24
GNA12	0.026	0.009	-10000	0	-10000	0	0
GNA13	0.028	0.005	-10000	0	-10000	0	0
CDC42	0.028	0.006	-10000	0	-10000	0	0

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.023	0.088	-9999	-0.4	18	18
E-cadherin/beta catenin	0.014	0.086	-9999	-0.45	16	16
CTNNB1	0.02	0.013	-9999	-10000	0	0
JUP	0.024	0.049	-9999	-0.61	3	3
CDH1	0.007	0.11	-9999	-0.59	17	17

Sphingosine 1-phosphate (S1P) pathway

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
SPHK2	0.026	0.04	-10000	0	-0.61	2	2
SPHK1	-0.014	0.14	-10000	0	-0.5	40	40
GNAI2	0.02	0.013	-10000	0	-10000	0	0
mol:S1P	0.007	0.052	-10000	0	-0.3	3	3
GNAO1	0.023	0.05	-10000	0	-0.53	4	4
mol:Sphinganine-1-P	-0.011	0.11	-10000	0	-0.37	41	41
growth factor activity	0	0	-10000	0	-10000	0	0
S1P/S1P2/G12/G13	0.047	0.054	-10000	0	-10000	0	0
GNAI3	0.028	0.005	-10000	0	-10000	0	0
G12/G13	0.037	0.015	-10000	0	-10000	0	0
S1PR3	0.028	0.006	-10000	0	-10000	0	0
S1PR2	0.029	0.003	-10000	0	-10000	0	0
EDG1	0	0	-10000	0	-10000	0	0
S1P1/S1P	0.001	0.044	-10000	0	-0.26	3	3
S1PR5	-0.062	0.2	-10000	0	-0.5	87	87
S1PR4	0.001	0.12	-10000	0	-0.5	26	26
GNAI1	0.024	0.03	-10000	0	-0.61	1	1
S1P/S1P5/G12	-0.013	0.12	-10000	0	-0.37	12	12
S1P/S1P3/Gq	0.02	0.086	-10000	0	-0.32	21	21
S1P/S1P4/Gi	0.014	0.066	0.3	1	-0.32	6	7
GNAQ	0.028	0.006	-10000	0	-10000	0	0
GNAZ	0.025	0.049	-10000	0	-0.61	3	3
GNA14	0.02	0.069	-10000	0	-0.61	6	6
GNA15	0.013	0.09	-10000	0	-0.5	15	15
GNA12	0.026	0.009	-10000	0	-10000	0	0
GNA13	0.028	0.005	-10000	0	-10000	0	0
GNA11	0.025	0.049	-10000	0	-0.61	3	3
ABCC1	0.028	0.006	-10000	0	-10000	0	0

a4b1 and a4b7 Integrin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.028	0.004	-9999	-10000	0	0
ITGB7	0.028	0.005	-9999	-10000	0	0
ITGA4	0.012	0.09	-9999	-0.5	15	15
alpha4/beta7 Integrin	0.028	0.069	-9999	-0.36	15	15
alpha4/beta1 Integrin	0.028	0.069	-9999	-0.36	15	15

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.031	0.069	-9999	-0.26	26	26
RGS9BP	-0.001	0.13	-9999	-0.61	23	23
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0.02	0.005	-9999	-10000	0	0
mol:Na +	0.022	0.044	-9999	-0.32	8	8
mol:ADP	0.003	0.03	-9999	-0.42	2	2
GNAT2	0.027	0.006	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.027	0.11	-9999	-0.36	34	34
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0.031	0.009	-9999	-10000	0	0
GRK7	0.022	0.038	-9999	-0.56	2	2
CNGB3	0.015	0.059	-9999	-0.52	6	6
Cone Metarhodopsin II/X-Arrestin	0.015	0.004	-9999	-10000	0	0
mol:Ca2+	-0.012	0.068	-9999	-0.38	10	10
Cone PDE6	0.043	0.1	-9999	-0.34	24	24
Cone Metarhodopsin II	0.026	0.024	-9999	-0.33	2	2
Na + (4 Units)	0.027	0.065	-9999	-0.36	12	12
GNAT2/GDP	0.037	0.096	-9999	-0.33	27	27
GNB5	0.029	0.003	-9999	-10000	0	0
mol:GMP (4 units)	0.009	0.039	-9999	-0.27	2	2
Cone Transducin	0.034	0.074	-9999	-0.28	26	26
SLC24A2	0.012	0.065	-9999	-0.54	7	7
GNB3/GNGT2	0.019	0.089	-9999	-0.36	26	26
GNB3	0.001	0.12	-9999	-0.5	25	25
GNAT2/GTP	0.02	0.004	-9999	-10000	0	0
CNGA3	0.018	0.041	-9999	-0.5	3	3
ARR3	0.021	0.005	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	0.022	0.044	-9999	-0.32	8	8
mol:Pi	0.026	0.11	-9999	-0.36	34	34
Cone CNG Channel	0.044	0.047	-9999	-0.34	1	1
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	0.012	0.065	-9999	-0.54	7	7
RGS9	0.013	0.091	-9999	-0.52	14	14
PDE6C	0.02	0.034	-9999	-0.5	2	2
GNGT2	0.027	0.024	-9999	-0.5	1	1
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.021	0.006	-9999	-10000	0	0

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

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
MET/RANBP9	0.035	0.029	-10000	0	-0.36	2	2
CRKL	0.046	0.097	0.4	8	-0.44	7	15
mol:PIP3	-0.008	0.045	-10000	0	-0.71	2	2
AKT1	0.001	0.057	-10000	0	-0.52	3	3
PTK2B	0.026	0.009	-10000	0	-10000	0	0
RAPGEF1	0.048	0.098	0.38	12	-0.41	7	19
RANBP10	0.028	0.006	-10000	0	-10000	0	0
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
HGF/MET/SHIP2	0.035	0.083	-10000	0	-0.36	20	20
MAP3K5	0.022	0.11	0.44	11	-0.44	5	16
HGF/MET/CIN85/CBL/ENDOPHILINS	0.049	0.085	-10000	0	-0.4	10	10
AP1	0.028	0.071	-10000	0	-0.38	12	12
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.027	0.006	-10000	0	-10000	0	0
apoptosis	-0.04	0.24	-10000	0	-0.71	53	53
STAT3 (dimer)	0.023	0.067	-10000	0	-0.4	5	5
GAB1/CRKL/SHP2/PI3K	0.061	0.086	0.43	1	-0.45	5	6
INPP5D	0.023	0.047	-10000	0	-0.5	4	4
CBL/CRK	0.06	0.098	0.35	11	-0.43	8	19
PTPN11	0.028	0.005	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.028	0.006	-10000	0	-10000	0	0
PTEN	0.028	0.006	-10000	0	-10000	0	0
ELK1	0.024	0.11	0.34	52	-0.22	1	53
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	0.021	0.041	-10000	0	-0.26	5	5
PAK1	0.003	0.057	0.38	1	-0.58	2	3
HGF/MET/RANBP10	0.035	0.082	-10000	0	-0.36	19	19
HRAS	0.017	0.097	-10000	0	-0.55	6	6
DOCK1	0.049	0.1	0.39	13	-0.43	8	21
GAB1	0.032	0.083	0.24	3	-0.42	9	12
CRK	0.044	0.092	0.31	9	-0.44	7	16
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	0.018	0.1	-10000	0	-0.54	11	11
JUN	0.028	0.006	-10000	0	-10000	0	0
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	0.008	0.039	-10000	0	-0.21	11	11
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
cell morphogenesis	0.076	0.14	0.38	54	-0.54	3	57
GRB2/SHC	0.037	0.043	-10000	0	-10000	0	0
FOS	0.012	0.096	-10000	0	-0.6	12	12
GLMN	0.004	0.001	-10000	0	-10000	0	0
cell motility	0.023	0.11	0.34	52	-0.22	1	53
HGF/MET/MUC20	0.019	0.079	-10000	0	-0.36	20	20
cell migration	0.036	0.042	-10000	0	-10000	0	0
GRB2	0.028	0.005	-10000	0	-10000	0	0
CBL	0.027	0.028	-10000	0	-0.61	1	1
MET/RANBP10	0.036	0.029	-10000	0	-0.36	2	2
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.021	0.058	-10000	0	-0.46	3	3
MET/MUC20	0.018	0.025	-10000	0	-0.36	2	2
RAP1B	0.055	0.11	0.44	18	-0.4	6	24
RAP1A	0.05	0.097	0.39	13	-0.45	3	16
HGF/MET/RANBP9	0.034	0.082	-10000	0	-0.35	20	20
RAF1	0.016	0.094	-10000	0	-0.52	6	6
STAT3	0.023	0.067	-10000	0	-0.41	5	5
cell proliferation	0.039	0.082	0.31	6	-0.44	5	11
RPS6KB1	0.012	0.037	-10000	0	-0.42	3	3
MAPK3	0.012	0.1	0.48	7	-10000	0	7
MAPK1	0.014	0.11	0.57	8	-10000	0	8
RANBP9	0.028	0.005	-10000	0	-10000	0	0
MAPK8	0.041	0.12	0.48	13	-0.43	6	19
SRC	0.017	0.054	-10000	0	-0.43	3	3
PI3K	0.034	0.052	-10000	0	-0.41	3	3
MET/Glomulin	0.017	0.03	-10000	0	-0.32	2	2
SOS1	0.028	0.005	-10000	0	-10000	0	0
MAP2K1	0.031	0.099	0.3	2	-0.49	5	7
MET	0.024	0.034	-10000	0	-0.5	2	2
MAP4K1	0.022	0.12	0.44	11	-0.43	8	19
PTK2	0.027	0.006	-10000	0	-10000	0	0
MAP2K2	0.032	0.1	0.36	4	-0.52	4	8
BAD	0.002	0.062	0.38	1	-0.58	3	4
MAP2K4	0.026	0.11	0.41	14	-0.42	4	18
SHP2/GRB2/SOS1/GAB1	0.042	0.066	-10000	0	-0.5	2	2
INPPL1	0.029	0.003	-10000	0	-10000	0	0
PXN	0.028	0.005	-10000	0	-10000	0	0
SH3KBP1	0.029	0.003	-10000	0	-10000	0	0
HGS	0.007	0.035	-10000	0	-0.25	1	1
PLCgamma1/PKC	0.021	0.004	-10000	0	-10000	0	0
HGF	0.003	0.11	-10000	0	-0.54	20	20
RASA1	0.024	0.03	-10000	0	-0.61	1	1
NCK1	0.026	0.029	-10000	0	-0.61	1	1
PTPRJ	0.029	0.003	-10000	0	-10000	0	0
NCK/PLCgamma1	0.038	0.051	-10000	0	-0.38	2	2
PDPK1	-0.001	0.06	-10000	0	-0.56	3	3
HGF/MET/SHIP	0.031	0.09	-10000	0	-0.36	23	23

mTOR signaling 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
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.028	0.006	-10000	0	-10000	0	0
mol:PIP3	0.005	0.046	-10000	0	-0.34	6	6
FRAP1	0.024	0.046	0.31	2	-10000	0	2
AKT1	0.019	0.066	0.22	7	-0.34	6	13
INSR	0.029	0.003	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.031	0.004	-10000	0	-10000	0	0
mol:GTP	0.041	0.064	0.3	1	-0.35	3	4
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0.013	0.026	-10000	0	-0.26	1	1
TSC2	0.027	0.006	-10000	0	-10000	0	0
RHEB/GDP	0.018	0.041	-10000	0	-0.35	2	2
TSC1	0.028	0.006	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.02	0.053	-10000	0	-0.24	13	13
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.026	0.034	-10000	0	-0.3	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.028	0.006	-10000	0	-10000	0	0
RPS6KB1	0.036	0.074	0.33	7	-0.37	3	10
MAP3K5	-0.005	0.051	0.17	1	-0.18	39	40
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
apoptosis	-0.005	0.051	0.17	1	-0.18	39	40
mol:LY294002	0	0	0.001	1	-0.001	21	22
EIF4B	0.04	0.079	0.33	14	-0.46	1	15
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.05	0.064	0.29	5	-0.58	1	6
eIF4E/eIF4G1/eIF4A1	0.02	0.019	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.031	0.058	-10000	0	-0.35	6	6
mTOR/RHEB/GTP/Raptor/GBL	0.023	0.047	0.23	8	-0.21	1	9
FKBP1A	0.028	0.005	-10000	0	-10000	0	0
RHEB/GTP	0.037	0.053	-10000	0	-0.34	2	2
mol:Amino Acids	0	0	0.001	1	-0.001	21	22
FKBP12/Rapamycin	0.021	0.005	-10000	0	-10000	0	0
PDPK1	0.004	0.05	0.19	4	-0.36	6	10
EIF4E	0.029	0.003	-10000	0	-10000	0	0
ASK1/PP5C	-0.001	0.16	-10000	0	-0.54	40	40
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.017	0.031	-10000	0	-10000	0	0
TSC1/TSC2	0.045	0.069	0.32	1	-0.38	3	4
tumor necrosis factor receptor activity	0	0	0.001	21	-0.001	1	22
RPS6	0.026	0.034	-10000	0	-0.5	2	2
PPP5C	0.029	0.003	-10000	0	-10000	0	0
EIF4G1	0.027	0.006	-10000	0	-10000	0	0
IRS1	0.002	0.053	-10000	0	-0.23	23	23
INS	0.018	0.002	-10000	0	-10000	0	0
PTEN	0.027	0.006	-10000	0	-10000	0	0
PDK2	0.007	0.049	0.2	7	-0.31	6	13
EIF4EBP1	-0.059	0.27	-10000	0	-1	39	39
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
PPP2R5D	0.027	0.05	0.33	5	-10000	0	5
peptide biosynthetic process	0.016	0.013	-10000	0	-10000	0	0
RHEB	0.026	0.009	-10000	0	-10000	0	0
EIF4A1	0.028	0.005	-10000	0	-10000	0	0
mol:Rapamycin	0.001	0.001	0.005	17	-0.003	1	18
EEF2	0.016	0.013	-10000	0	-10000	0	0
eIF4E/4E-BP1	-0.04	0.26	-10000	0	-0.93	39	39

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.029	0.003	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	0.041	0.091	-9999	-0.63	1	1
Syndecan-3/Neurocan	0.014	0.084	-9999	-0.36	19	19
POMC	0.025	0.041	-9999	-0.62	2	2
EGFR	0.019	0.06	-9999	-0.52	6	6
Syndecan-3/EGFR	0.017	0.077	-9999	-0.36	15	15
AGRP	0.021	0.04	-9999	-0.61	2	2
NCSTN	0.027	0.006	-9999	-10000	0	0
PSENEN	0.029	0.003	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.029	0.003	-9999	-10000	0	0
APH1A	0.027	0.006	-9999	-10000	0	0
NCAN	0.014	0.077	-9999	-0.5	11	11
long-term memory	0.038	0.073	-9999	-0.33	8	8
Syndecan-3/IL8	0.003	0.1	-9999	-0.34	27	27
PSEN1	0.027	0.008	-9999	-10000	0	0
Src/Cortactin	0.041	0.009	-9999	-10000	0	0
FYN	0.027	0.008	-9999	-10000	0	0
limb bud formation	0.006	0.069	-9999	-0.36	17	17
MC4R	0.012	0.069	-9999	-0.5	9	9
SRC	0.028	0.006	-9999	-10000	0	0
PTN	0.01	0.1	-9999	-0.6	13	13
FGFR/FGF/Syndecan-3	0.006	0.069	-9999	-0.36	17	17
neuron projection morphogenesis	0.022	0.099	-9999	-0.57	2	2
Syndecan-3/AgRP	0.017	0.076	-9999	-0.34	21	21
Syndecan-3/AgRP/MC4R	0.025	0.085	-9999	-0.34	16	16
Fyn/Cortactin	0.04	0.012	-9999	-10000	0	0
SDC3	0.006	0.07	-9999	-0.37	17	17
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	0.003	0.099	-9999	-0.33	27	27
IL8	-0.009	0.14	-9999	-0.53	34	34
Syndecan-3/Fyn/Cortactin	0.039	0.075	-9999	-0.34	8	8
Syndecan-3/CASK	0.003	0.069	-9999	-0.34	19	19
alpha-MSH/MC4R	0.026	0.061	-9999	-0.38	11	11
Gamma Secretase	0.076	0.029	-9999	-10000	0	0

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.034	0.068	0.24	18	-0.34	2	20
adherens junction organization	-0.001	0.09	0.25	5	-0.45	4	9
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.038	0.075	0.26	18	-0.34	1	19
FMN1	-0.017	0.098	-10000	0	-0.41	12	12
mol:IP3	0.021	0.052	-10000	0	-0.32	3	3
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.003	0.077	-10000	0	-0.49	3	3
CTNNB1	0.021	0.014	-10000	0	-10000	0	0
AKT1	0.022	0.059	0.26	1	-0.35	1	2
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.052	0.14	-10000	0	-0.56	19	19
CTNND1	0.03	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.003	0.071	-10000	0	-0.4	4	4
VASP	-0.003	0.073	-10000	0	-0.47	3	3
ZYX	-0.003	0.072	-10000	0	-0.47	3	3
JUB	-0.005	0.073	-10000	0	-0.47	3	3
EGFR(dimer)	0.004	0.082	-10000	0	-0.45	4	4
E-cadherin/beta catenin-gamma catenin	0.022	0.083	-10000	0	-0.38	18	18
mol:PI-3-4-5-P3	0.03	0.068	0.26	2	-0.33	5	7
PIK3CA	0.029	0.03	-10000	0	-0.61	1	1
PI3K	0.031	0.069	0.27	2	-0.34	5	7
FYN	-0.19	0.14	0.23	5	-0.38	76	81
mol:Ca2+	0.021	0.051	-10000	0	-0.32	3	3
JUP	0.027	0.049	-10000	0	-0.61	3	3
PIK3R1	0.027	0.03	-10000	0	-0.61	1	1
mol:DAG	0.021	0.052	-10000	0	-0.32	3	3
CDH1	0.009	0.11	-10000	0	-0.59	17	17
RhoA/GDP	0.037	0.074	0.26	18	-0.34	1	19
establishment of polarity of embryonic epithelium	-0.003	0.072	-10000	0	-0.46	3	3
SRC	0.028	0.006	-10000	0	-10000	0	0
RAC1	0.026	0.009	-10000	0	-10000	0	0
RHOA	0.021	0.013	-10000	0	-10000	0	0
EGFR	0.019	0.06	-10000	0	-0.52	6	6
CASR	-0.21	0.14	0.23	4	-0.36	65	69
RhoA/GTP	0.027	0.05	-10000	0	-0.31	2	2
AKT2	0.023	0.063	0.26	2	-0.37	2	4
actin cable formation	-0.016	0.095	-10000	0	-0.43	9	9
apoptosis	-0.024	0.071	0.32	4	-0.33	7	11
CTNNA1	0.023	0.013	-10000	0	-10000	0	0
mol:GDP	0.012	0.056	-10000	0	-0.34	3	3
PIP5K1A	-0.003	0.072	-10000	0	-0.41	4	4
PLCG1	0.021	0.053	-10000	0	-0.33	3	3
Rac1/GTP	0.015	0.082	-10000	0	-0.42	4	4
homophilic cell adhesion	0.001	0.003	-10000	0	-10000	0	0

Ephrin B reverse signaling

Figure S93. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S93. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.028	0.004	-10000	0	-10000	0	0
EPHB2	0.019	0.07	-10000	0	-0.48	9	9
EFNB1	0.013	0.052	-10000	0	-0.37	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.052	0.067	-10000	0	-0.52	2	2
Ephrin B2/EPHB1-2	0.043	0.055	-10000	0	-0.43	5	5
neuron projection morphogenesis	0.034	0.059	-10000	0	-0.5	2	2
Ephrin B1/EPHB1-2/Tiam1	0.048	0.068	-10000	0	-0.56	2	2
DNM1	0.018	0.071	-10000	0	-0.51	9	9
cell-cell signaling	0	0.002	-10000	0	-10000	0	0
MAP2K4	0	0.087	-10000	0	-0.5	14	14
YES1	-0.001	0.12	-10000	0	-0.74	14	14
Ephrin B1/EPHB1-2/NCK2	0.048	0.068	-10000	0	-0.55	2	2
PI3K	0.027	0.097	-10000	0	-0.51	14	14
mol:GDP	0.047	0.067	-10000	0	-0.55	2	2
ITGA2B	0.009	0.099	-10000	0	-0.51	18	18
endothelial cell proliferation	0.034	0.013	-10000	0	-10000	0	0
FYN	-0.003	0.13	-10000	0	-0.75	14	14
MAP3K7	-0.004	0.09	-10000	0	-0.55	13	13
FGR	-0.001	0.12	-10000	0	-0.73	14	14
TIAM1	0.028	0.006	-10000	0	-10000	0	0
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
RGS3	0.028	0.006	-10000	0	-10000	0	0
cell adhesion	0.014	0.11	-10000	0	-0.58	10	10
LYN	-0.001	0.12	-10000	0	-0.74	14	14
Ephrin B1/EPHB1-2/Src Family Kinases	-0.006	0.12	-10000	0	-0.69	14	14
Ephrin B1/EPHB1-2	-0.007	0.1	-10000	0	-0.59	14	14
SRC	0.001	0.12	-10000	0	-0.72	14	14
ITGB3	0.024	0.049	-10000	0	-0.61	3	3
EPHB1	0.023	0.047	-10000	0	-0.58	3	3
EPHB4	0.026	0.009	-10000	0	-10000	0	0
RAC1	0.026	0.009	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.034	0.013	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	0.024	0.084	-10000	0	-0.38	21	21
BLK	-0.004	0.12	-10000	0	-0.74	14	14
HCK	-0.002	0.12	-10000	0	-0.72	14	14
regulation of stress fiber formation	-0.046	0.067	0.54	2	-10000	0	2
MAPK8	0.003	0.087	0.4	1	-0.49	12	13
Ephrin B1/EPHB1-2/RGS3	0.049	0.069	-10000	0	-0.56	2	2
endothelial cell migration	0.015	0.097	0.39	4	-0.48	11	15
NCK2	0.028	0.005	-10000	0	-10000	0	0
PTPN13	0.015	0.097	-10000	0	-0.71	9	9
regulation of focal adhesion formation	-0.046	0.067	0.54	2	-10000	0	2
chemotaxis	-0.047	0.067	0.55	2	-10000	0	2
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
Rac1/GTP	0.044	0.063	-10000	0	-0.51	2	2
angiogenesis	-0.006	0.099	-10000	0	-0.59	14	14
LCK	-0.003	0.13	-10000	0	-0.75	14	14

Canonical NF-kappaB 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
FBXW11	0.024	0.014	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.039	0.07	0.3	9	-10000	0	9
ERC1	0.028	0.006	-10000	0	-10000	0	0
RIP2/NOD2	-0.055	0.17	-10000	0	-0.36	116	116
NFKBIA	0.021	0.021	-10000	0	-10000	0	0
BIRC2	0.028	0.004	-10000	0	-10000	0	0
IKBKB	0.027	0.008	-10000	0	-10000	0	0
RIPK2	0.026	0.024	-10000	0	-0.5	1	1
IKBKG	0.012	0.056	-10000	0	-10000	0	0
IKK complex/A20	0.035	0.088	-10000	0	-0.47	1	1
NEMO/A20/RIP2	0.026	0.024	-10000	0	-0.5	1	1
XPO1	0.028	0.005	-10000	0	-10000	0	0
NEMO/ATM	0.024	0.077	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.028	0.005	-10000	0	-10000	0	0
Exportin 1/RanGTP	0.037	0.01	-10000	0	-10000	0	0
IKK complex/ELKS	0.026	0.068	-10000	0	-10000	0	0
BCL10/MALT1/TRAF6	0.055	0.014	-10000	0	-10000	0	0
NOD2	-0.098	0.23	-10000	0	-0.5	120	120
NFKB1	0.031	0.028	-10000	0	-0.6	1	1
RELA	0.032	0.003	-10000	0	-10000	0	0
MALT1	0.028	0.005	-10000	0	-10000	0	0
cIAP1/UbcH5C	0.042	0.007	-10000	0	-10000	0	0
ATM	0.027	0.028	-10000	0	-0.61	1	1
TNF/TNFR1A	0.033	0.057	-10000	0	-0.41	8	8
TRAF6	0.029	0.003	-10000	0	-10000	0	0
PRKCA	0.028	0.005	-10000	0	-10000	0	0
CHUK	0.028	0.006	-10000	0	-10000	0	0
UBE2D3	0.028	0.004	-10000	0	-10000	0	0
TNF	0.018	0.073	-10000	0	-0.56	8	8
NF kappa B1 p50/RelA	0.05	0.036	-10000	0	-0.37	1	1
BCL10	0.028	0.005	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.021	0.021	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.024	0.014	-10000	0	-10000	0	0
TNFRSF1A	0.028	0.006	-10000	0	-10000	0	0
IKK complex	0.032	0.077	-10000	0	-10000	0	0
CYLD	0.028	0.006	-10000	0	-10000	0	0
IKK complex/PKC alpha	0.039	0.08	-10000	0	-10000	0	0

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.036	0.01	-10000	0	-10000	0	0
PRKCZ	0.024	0.049	-10000	0	-0.61	3	3
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.028	0.006	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.023	0.096	-10000	0	-0.34	2	2
IRAK/TOLLIP	0.035	0.011	-10000	0	-10000	0	0
IKBKB	0.027	0.008	-10000	0	-10000	0	0
IKBKG	0.028	0.004	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.018	0.15	-10000	0	-0.41	65	65
IL1A	0.014	0.081	-10000	0	-0.5	12	12
IL1B	0.015	0.043	-10000	0	-0.38	6	6
IRAK/TRAF6/p62/Atypical PKCs	0.052	0.043	-10000	0	-10000	0	0
IL1R2	-0.036	0.18	-10000	0	-0.56	56	56
IL1R1	0.028	0.005	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.006	0.046	-10000	0	-10000	0	0
TOLLIP	0.029	0.003	-10000	0	-10000	0	0
TICAM2	0.023	0.012	-10000	0	-10000	0	0
MAP3K3	0.028	0.005	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.018	0.005	-10000	0	-10000	0	0
IKK complex/ELKS	0.052	0.063	0.38	1	-10000	0	1
JUN	0.019	0.058	0.35	10	-10000	0	10
MAP3K7	0.027	0.007	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.062	0.059	-10000	0	-0.62	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88	0.04	0.066	-10000	0	-0.36	1	1
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.046	0.067	-10000	0	-0.34	1	1
IL1 beta fragment/IL1R1/IL1RAP	0.042	0.048	-10000	0	-0.35	2	2
NFKB1	0.027	0.029	-10000	0	-0.61	1	1
MAPK8	0.023	0.061	0.36	10	-10000	0	10
IRAK1	0.019	0.007	-10000	0	-10000	0	0
IL1RN/IL1R1	0.028	0.074	-10000	0	-0.37	17	17
IRAK4	0.028	0.005	-10000	0	-10000	0	0
PRKCI	0.027	0.007	-10000	0	-10000	0	0
TRAF6	0.029	0.003	-10000	0	-10000	0	0
PI3K	0.036	0.034	-10000	0	-0.45	2	2
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.008	0.077	-10000	0	-0.35	1	1
CHUK	0.028	0.006	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.042	0.048	-10000	0	-0.35	2	2
IL1 beta/IL1R2	-0.006	0.13	-10000	0	-0.35	59	59
IRAK/TRAF6/TAK1/TAB1/TAB2	0.04	0.015	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.047	0.059	-10000	0	-0.85	1	1
IRAK3	0.028	0.005	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.053	0.054	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.022	0.038	-10000	0	-0.3	1	1
IL1 alpha/IL1R1/IL1RAP	0.042	0.064	-10000	0	-0.31	15	15
RELA	0.029	0.003	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.021	0.013	-10000	0	-10000	0	0
MYD88	0.02	0.013	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0.051	0.02	-10000	0	-10000	0	0
IL1RAP	0.023	0.05	-10000	0	-0.53	4	4
UBE2N	0.028	0.005	-10000	0	-10000	0	0
IRAK/TRAF6	0.028	0.038	-10000	0	-10000	0	0
CASP1	0.028	0.004	-10000	0	-10000	0	0
IL1RN/IL1R2	-0.021	0.16	-10000	0	-0.41	69	69
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.04	0.053	-10000	0	-0.33	2	2
TMEM189-UBE2V1	0.022	0.007	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.02	0.099	-10000	0	-10000	0	0
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
IL1RN	0.01	0.097	-10000	0	-0.51	17	17
TRAF6/TAK1/TAB1/TAB2	0.048	0.017	-10000	0	-10000	0	0
MAP2K6	0.03	0.06	0.36	10	-10000	0	10

E-cadherin signaling in the nascent adherens junction

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
CTTN	-0.025	0.12	-10000	0	-0.47	16	16
KLHL20	0.016	0.073	0.2	2	-0.3	2	4
CYFIP2	0.013	0.075	-10000	0	-0.61	7	7
Rac1/GDP	0.018	0.086	0.29	6	-0.35	1	7
ENAH	-0.024	0.12	-10000	0	-0.47	17	17
AP1M1	0.029	0.003	-10000	0	-10000	0	0
RAP1B	0.028	0.005	-10000	0	-10000	0	0
RAP1A	0.028	0.005	-10000	0	-10000	0	0
CTNNB1	0.021	0.013	-10000	0	-10000	0	0
CDC42/GTP	0.023	0.052	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.013	0.034	-10000	0	-0.2	4	4
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.036	0.078	-10000	0	-0.35	16	16
RAPGEF1	-0.017	0.12	0.27	4	-0.42	11	15
CTNND1	0.029	0.003	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.025	0.13	-10000	0	-0.49	17	17
CRK	-0.026	0.12	-10000	0	-0.44	14	14
E-cadherin/gamma catenin/alpha catenin	0.028	0.084	-10000	0	-0.41	15	15
alphaE/beta7 Integrin	0.041	0.01	-10000	0	-10000	0	0
IQGAP1	0.029	0.003	-10000	0	-10000	0	0
NCKAP1	0.028	0.006	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.049	0.019	-10000	0	-10000	0	0
DLG1	-0.021	0.12	-10000	0	-0.47	15	15
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.006	0.028	-10000	0	-10000	0	0
MLLT4	0.026	0.008	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.049	0.019	-10000	0	-10000	0	0
PI3K	0.005	0.041	-10000	0	-10000	0	0
ARF6	0.027	0.008	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
E-cadherin/gamma catenin	0.022	0.097	-10000	0	-0.47	18	18
TIAM1	0.028	0.006	-10000	0	-10000	0	0
E-cadherin(dimer)/Ca2+	0.03	0.069	-10000	0	-0.33	13	13
AKT1	0.016	0.03	-10000	0	-10000	0	0
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
CDH1	0.007	0.11	-10000	0	-0.59	17	17
RhoA/GDP	0.036	0.083	0.33	10	-10000	0	10
actin cytoskeleton organization	0.018	0.061	0.17	14	-0.22	2	16
CDC42/GDP	0.026	0.11	0.37	15	-0.35	1	16
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.01	0.061	-10000	0	-0.3	15	15
ITGB7	0.028	0.005	-10000	0	-10000	0	0
RAC1	0.026	0.009	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.033	0.074	-10000	0	-0.35	13	13
E-cadherin/Ca2+/beta catenin/alpha catenin	0.02	0.064	-10000	0	-0.33	13	13
mol:GDP	0.014	0.11	0.41	12	-0.4	3	15
CDC42/GTP/IQGAP1	0.037	0.009	-10000	0	-10000	0	0
JUP	0.024	0.049	-10000	0	-0.61	3	3
p120 catenin/RhoA/GDP	0.014	0.08	0.3	3	-10000	0	3
RAC1/GTP/IQGAP1	0.035	0.012	-10000	0	-10000	0	0
PIP5K1C/AP1M1	0.042	0.005	-10000	0	-10000	0	0
RHOA	0.021	0.013	-10000	0	-10000	0	0
CDC42	0.028	0.006	-10000	0	-10000	0	0
CTNNA1	0.022	0.012	-10000	0	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.017	0.059	0.16	16	-0.2	18	34
NME1	0.028	0.005	-10000	0	-10000	0	0
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	-0.025	0.12	-10000	0	-0.48	16	16
regulation of cell-cell adhesion	0.01	0.04	-10000	0	-10000	0	0
WASF2	0.012	0.03	-10000	0	-10000	0	0
Rap1/GTP	0.03	0.064	0.25	5	-10000	0	5
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.048	0.083	-10000	0	-0.63	1	1
CCND1	0.017	0.069	0.18	12	-0.24	18	30
VAV2	-0.023	0.16	-10000	0	-0.57	17	17
RAP1/GDP	0.037	0.075	0.27	6	-10000	0	6
adherens junction assembly	-0.024	0.12	-10000	0	-0.46	16	16
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.028	0.004	-10000	0	-10000	0	0
PIP5K1C	0.029	0.003	-10000	0	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.045	0.087	-10000	0	-0.61	1	1
E-cadherin/beta catenin	-0.001	0.075	-10000	0	-0.4	17	17
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	-0.024	0.12	-10000	0	-0.47	16	16
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
Rac1/GTP	-0.033	0.077	-10000	0	-0.38	5	5
E-cadherin/beta catenin/alpha catenin	0.023	0.074	-10000	0	-0.38	13	13
ITGAE	0.028	0.005	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.026	0.13	-10000	0	-0.5	17	17

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.022	0.057	-10000	0	-0.5	6	6
mol:Halofuginone	0.005	0.001	-10000	0	-10000	0	0
ITGA1	0.026	0.008	-10000	0	-10000	0	0
CDKN1A	0.016	0.046	-10000	0	-10000	0	0
PRL-3/alpha Tubulin	0.027	0.071	-10000	0	-0.36	16	16
mol:Ca2+	-0.022	0.084	0.22	16	-0.38	19	35
AGT	0.004	0.11	-10000	0	-0.5	23	23
CCNA2	-0.037	0.11	-10000	0	-0.56	5	5
TUBA1B	0.028	0.005	-10000	0	-10000	0	0
EGR1	0.01	0.058	-10000	0	-0.44	8	8
CDK2/Cyclin E1	0.057	0.1	-10000	0	-0.42	10	10
MAPK3	0.007	0.067	-10000	0	-0.36	16	16
PRL-2 /Rab GGTase beta	0.041	0.009	-10000	0	-10000	0	0
MAPK1	0.008	0.067	-10000	0	-0.36	16	16
PTP4A1	0.008	0.041	-10000	0	-10000	0	0
PTP4A3	0.011	0.093	-10000	0	-0.5	16	16
PTP4A2	0.028	0.006	-10000	0	-10000	0	0
ITGB1	0.008	0.067	-10000	0	-0.36	16	16
SRC	0.028	0.006	-10000	0	-10000	0	0
RAC1	0.016	0.032	-10000	0	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0.037	0.033	-10000	0	-0.45	2	2
PRL-1/ATF-5	0.06	0.084	-10000	0	-10000	0	0
RABGGTA	0.025	0.04	-10000	0	-0.61	2	2
BCAR1	-0.008	0.046	0.22	16	-0.47	1	17
RHOC	0.014	0.049	-10000	0	-0.57	1	1
RHOA	-0.027	0.11	-10000	0	-0.55	3	3
cell motility	0.019	0.088	0.29	7	-0.34	6	13
PRL-1/alpha Tubulin	0.06	0.079	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	0.025	0.069	-10000	0	-0.36	15	15
ROCK1	0.019	0.082	0.27	6	-0.32	4	10
RABGGTB	0.028	0.006	-10000	0	-10000	0	0
CDK2	0.028	0.005	-10000	0	-10000	0	0
mitosis	0.008	0.041	-10000	0	-10000	0	0
ATF5	0.025	0.041	-10000	0	-0.5	3	3

ErbB2/ErbB3 signaling events

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
USP8	0.008	0.006	-10000	0	-10000	0	0
RAS family/GTP	0.011	0.091	-10000	0	-0.48	7	7
NFATC4	0.004	0.063	0.27	7	-0.44	1	8
ERBB2IP	0.026	0.009	-10000	0	-10000	0	0
HSP90 (dimer)	0.027	0.008	-10000	0	-10000	0	0
mammary gland morphogenesis	0.012	0.069	-10000	0	-10000	0	0
JUN	0.016	0.06	0.26	3	-0.27	2	5
HRAS	0.027	0.024	-10000	0	-0.5	1	1
DOCK7	0.002	0.066	-10000	0	-0.55	1	1
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.026	0.078	-10000	0	-0.34	19	19
AKT1	0.009	0.005	-10000	0	-10000	0	0
BAD	0.007	0.023	-10000	0	-0.35	2	2
MAPK10	0.014	0.055	0.2	7	-0.3	2	9
mol:GTP	-0.001	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	0.014	0.075	-10000	0	-10000	0	0
RAF1	-0.008	0.083	0.28	2	-0.49	6	8
ErbB2/ErbB3/neuregulin 2	0.015	0.066	-10000	0	-0.33	16	16
STAT3	0.026	0.1	-10000	0	-0.89	6	6
cell migration	0.034	0.083	0.27	27	-0.26	2	29
mol:PI-3-4-5-P3	0	0.002	-10000	0	-10000	0	0
cell proliferation	-0.11	0.17	-10000	0	-0.5	12	12
FOS	-0.066	0.13	0.29	1	-0.48	12	13
NRAS	0.027	0.005	-10000	0	-10000	0	0
mol:Ca2+	0.012	0.069	-10000	0	-10000	0	0
MAPK3	-0.086	0.15	0.34	1	-0.51	7	8
MAPK1	-0.086	0.15	0.37	1	-0.56	8	9
JAK2	0.004	0.062	-10000	0	-10000	0	0
NF2	0.016	0.037	-10000	0	-0.78	1	1
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0.007	0.083	-10000	0	-0.39	17	17
NRG1	0.009	0.1	-10000	0	-0.55	15	15
GRB2/SOS1	0.04	0.009	-10000	0	-10000	0	0
MAPK8	0.007	0.074	-10000	0	-0.34	5	5
MAPK9	0.008	0.043	0.2	5	-0.26	1	6
ERBB2	-0.016	0.029	-10000	0	-0.47	2	2
ERBB3	0.017	0.079	-10000	0	-0.61	8	8
SHC1	0.027	0.006	-10000	0	-10000	0	0
RAC1	0.026	0.009	-10000	0	-10000	0	0
apoptosis	-0.005	0.021	0.25	2	-0.17	2	4
STAT3 (dimer)	0.026	0.098	-10000	0	-0.87	6	6
RNF41	0.006	0.005	-10000	0	-10000	0	0
FRAP1	0.004	0.003	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0.007	0.047	-10000	0	-0.38	1	1
ErbB2/ErbB2/HSP90 (dimer)	0.015	0.028	-10000	0	-0.4	2	2
CHRNA1	-0.11	0.17	0.33	1	-0.39	55	56
myelination	0.002	0.077	0.34	11	-0.39	1	12
PPP3CB	0.004	0.06	-10000	0	-10000	0	0
KRAS	0.027	0.005	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0.031	0.084	-10000	0	-0.49	6	6
NRG2	0.012	0.072	-10000	0	-0.52	9	9
mol:GDP	0.007	0.085	-10000	0	-0.38	18	18
SOS1	0.028	0.005	-10000	0	-10000	0	0
MAP2K2	-0.016	0.085	0.27	3	-0.46	6	9
SRC	0.028	0.006	-10000	0	-10000	0	0
mol:cAMP	0	0.001	-10000	0	-10000	0	0
PTPN11	0.005	0.063	-10000	0	-10000	0	0
MAP2K1	-0.11	0.17	-10000	0	-0.53	14	14
heart morphogenesis	0.012	0.069	-10000	0	-10000	0	0
RAS family/GDP	0.038	0.089	-10000	0	-0.51	6	6
GRB2	0.028	0.005	-10000	0	-10000	0	0
PRKACA	0.016	0.038	-10000	0	-0.82	1	1
CHRNE	0.011	0.02	0.14	2	-0.17	2	4
HSP90AA1	0.027	0.008	-10000	0	-10000	0	0
activation of caspase activity	-0.009	0.005	-10000	0	-10000	0	0
nervous system development	0.012	0.069	-10000	0	-10000	0	0
CDC42	0.028	0.006	-10000	0	-10000	0	0

Cellular roles of Anthrax toxin

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
ANTXR1	0.027	0.016	-10000	0	-0.3	1	1
ANTXR2	0.029	0.003	-10000	0	-10000	0	0
negative regulation of myeloid dendritic cell antigen processing and presentation	0.001	0.002	-10000	0	-10000	0	0
monocyte activation	0	0.099	-10000	0	-0.37	29	29
MAP2K2	0.013	0.061	-10000	0	-0.59	5	5
MAP2K1	0.003	0.002	-10000	0	-10000	0	0
MAP2K7	0.003	0.002	-10000	0	-10000	0	0
MAP2K6	0.001	0.025	-10000	0	-0.32	3	3
CYAA	0.004	0.006	-10000	0	-10000	0	0
MAP2K4	0.003	0.001	-10000	0	-10000	0	0
IL1B	0.004	0.041	0.24	6	-0.26	6	12
Channel	0.035	0.011	-10000	0	-10000	0	0
NLRP1	0	0.028	-10000	0	-0.28	5	5
CALM1	0.027	0.008	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.009	0.096	-10000	0	-0.37	33	33
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	-0.001	0.002	-10000	0	-10000	0	0
MAPK3	0.003	0.002	-10000	0	-10000	0	0
MAPK1	0.003	0.002	-10000	0	-10000	0	0
PGR	-0.008	0.058	-10000	0	-0.33	16	16
PA/Cellular Receptors	0.037	0.012	-10000	0	-10000	0	0
apoptosis	0.001	0.002	-10000	0	-10000	0	0
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.034	0.011	-10000	0	-10000	0	0
macrophage activation	0.003	0.002	-10000	0	-10000	0	0
TNF	0.018	0.073	-10000	0	-0.56	8	8
VCAM1	0.005	0.088	-10000	0	-0.37	22	22
platelet activation	-0.009	0.096	-10000	0	-0.37	33	33
MAPKKK cascade	-0.008	0.019	-10000	0	-0.14	4	4
IL18	0.003	0.03	-10000	0	-0.26	5	5
negative regulation of macrophage activation	0.001	0.002	-10000	0	-10000	0	0
LEF	0.001	0.002	-10000	0	-10000	0	0
CASP1	0.004	0.014	-10000	0	-0.14	5	5
mol:cAMP	-0.009	0.097	-10000	0	-0.38	33	33
necrosis	0.001	0.002	-10000	0	-10000	0	0
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.035	0.011	-10000	0	-10000	0	0
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	0.041	0.11	0.28	1	-0.5	10	11
CaM/Ca2+	0.02	0.006	-10000	0	-10000	0	0
AKT1	0.027	0.008	-10000	0	-10000	0	0
AKT2	0.029	0.003	-10000	0	-10000	0	0
STXBP4	0.028	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.034	0.13	0.3	9	-0.48	17	26
YWHAZ	0.027	0.007	-10000	0	-10000	0	0
CALM1	0.027	0.008	-10000	0	-10000	0	0
YWHAQ	0.028	0.005	-10000	0	-10000	0	0
TBC1D4	0.019	0.006	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.028	0.004	-10000	0	-10000	0	0
YWHAB	0.028	0.006	-10000	0	-10000	0	0
SNARE/Synip	0.054	0.016	-10000	0	-10000	0	0
YWHAG	0.026	0.009	-10000	0	-10000	0	0
ASIP	-0.018	0.15	-10000	0	-0.5	42	42
PRKCI	0.027	0.007	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0.02	0.006	-10000	0	-10000	0	0
RHOQ	0.028	0.005	-10000	0	-10000	0	0
GYS1	0.02	0.008	-10000	0	-10000	0	0
PRKCZ	0.024	0.049	-10000	0	-0.61	3	3
TRIP10	0.029	0.003	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.037	0.008	-10000	0	-10000	0	0
AS160/14-3-3	0.017	0.064	-10000	0	-0.36	5	5
VAMP2	0.028	0.005	-10000	0	-10000	0	0
SLC2A4	0.033	0.14	0.35	5	-0.53	18	23
STX4	0.028	0.006	-10000	0	-10000	0	0
GSK3B	0.025	0.01	-10000	0	-10000	0	0
SFN	-0.036	0.18	-10000	0	-0.52	59	59
LNPEP	0.022	0.041	-10000	0	-0.61	2	2
YWHAE	0.028	0.005	-10000	0	-10000	0	0

Signaling events mediated by HDAC Class III

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
EP300	0.027	0.029	-10000	0	-0.61	1	1
HDAC4	0.027	0.007	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.016	0.023	0.34	2	-10000	0	2
CDKN1A	-0.005	0.021	-10000	0	-0.33	2	2
KAT2B	0.019	0.031	-10000	0	-0.61	1	1
BAX	0.029	0.003	-10000	0	-10000	0	0
FOXO3	-0.006	0.021	0.45	1	-10000	0	1
FOXO1	0.028	0.005	-10000	0	-10000	0	0
FOXO4	0.021	0.015	-10000	0	-0.3	1	1
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.028	0.004	-10000	0	-10000	0	0
TAT	0.015	0.074	-10000	0	-0.5	10	10
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.012	0.088	-10000	0	-0.36	30	30
PPARGC1A	-0.034	0.19	-10000	0	-0.6	50	50
FHL2	0.023	0.054	-10000	0	-0.58	4	4
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.038	0.01	-10000	0	-10000	0	0
HIST2H4A	0.016	0.023	-10000	0	-0.34	2	2
SIRT1/FOXO3a	0.01	0.028	0.3	1	-10000	0	1
SIRT1	0.024	0.007	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.049	0.018	-10000	0	-10000	0	0
SIRT1/Histone H1b	0.032	0.03	-10000	0	-0.26	1	1
apoptosis	-0.052	0.014	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.007	0.12	-10000	0	-0.39	49	49
p53/SIRT1	0.028	0.016	-10000	0	-10000	0	0
SIRT1/FOXO4	0.035	0.024	-10000	0	-0.26	1	1
FOXO1/FHL2/SIRT1	0.046	0.036	-10000	0	-0.33	4	4
HIST1H1E	0.019	0.018	-10000	0	-0.3	1	1
SIRT1/p300	0.037	0.024	-10000	0	-0.45	1	1
muscle cell differentiation	-0.005	0.08	0.31	23	-10000	0	23
TP53	0.024	0.007	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0.052	0.014	-10000	0	-10000	0	0
CREBBP	0.028	0.006	-10000	0	-10000	0	0
MEF2D	0.027	0.006	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.028	0.056	-10000	0	-0.36	10	10
ACSS2	0.017	0.005	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	0.005	0.08	-10000	0	-0.31	23	23

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.005	0.12	-10000	0	-0.38	42	42
cell-cell adhesion	-0.003	0.049	0.45	2	-10000	0	2
Ephrin B/EPHB2/RasGAP	0.062	0.066	-10000	0	-10000	0	0
ITSN1	0.028	0.006	-10000	0	-10000	0	0
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
SHC1	0.027	0.006	-10000	0	-10000	0	0
Ephrin B1/EPHB3	0.028	0.062	-10000	0	-0.39	11	11
Ephrin B1/EPHB1	0.034	0.032	-10000	0	-0.36	3	3
HRAS/GDP	0.032	0.056	-10000	0	-0.47	1	1
Ephrin B/EPHB1/GRB7	0.067	0.069	-10000	0	-10000	0	0
Endophilin/SYNJ1	0.018	0.053	-10000	0	-10000	0	0
KRAS	0.028	0.005	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	0.069	0.059	-10000	0	-0.33	7	7
endothelial cell migration	0.048	0.034	-10000	0	-0.33	2	2
GRB2	0.028	0.005	-10000	0	-10000	0	0
GRB7	0.021	0.069	-10000	0	-0.61	6	6
PAK1	0.024	0.053	-10000	0	-10000	0	0
HRAS	0.028	0.024	-10000	0	-0.5	1	1
RRAS	0.019	0.052	-10000	0	-10000	0	0
DNM1	0.018	0.072	-10000	0	-0.52	9	9
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	0.022	0.05	-10000	0	-10000	0	0
lamellipodium assembly	0.003	0.049	-10000	0	-0.45	2	2
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.034	0.045	-10000	0	-0.43	1	1
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
EPHB2	0.019	0.07	-10000	0	-0.48	9	9
EPHB3	0.014	0.093	-10000	0	-0.61	11	11
EPHB1	0.024	0.047	-10000	0	-0.57	3	3
EPHB4	0.026	0.009	-10000	0	-10000	0	0
mol:GDP	0.019	0.054	0.33	3	-0.46	1	4
Ephrin B/EPHB2	0.056	0.057	-10000	0	-0.33	9	9
Ephrin B/EPHB3	0.05	0.076	-10000	0	-0.35	16	16
JNK cascade	0.022	0.061	0.36	5	-0.54	2	7
Ephrin B/EPHB1	0.056	0.055	-10000	0	-0.33	8	8
RAP1/GDP	0.06	0.077	0.35	5	-0.39	1	6
EFNB2	0.028	0.004	-10000	0	-10000	0	0
EFNB3	0.02	0.071	-10000	0	-0.57	7	7
EFNB1	0.029	0.002	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	0.044	0.056	-10000	0	-0.43	5	5
RAP1B	0.028	0.005	-10000	0	-10000	0	0
RAP1A	0.028	0.005	-10000	0	-10000	0	0
CDC42/GTP	0.043	0.069	-10000	0	-0.52	2	2
Rap1/GTP	0.021	0.054	-10000	0	-0.54	1	1
axon guidance	-0.005	0.11	-10000	0	-0.38	42	42
MAPK3	0.027	0.043	-10000	0	-0.39	1	1
MAPK1	0.028	0.043	-10000	0	-0.39	1	1
Rac1/GDP	0.034	0.061	0.36	2	-0.42	1	3
actin cytoskeleton reorganization	0.007	0.046	-10000	0	-0.38	3	3
CDC42/GDP	0.052	0.08	0.33	7	-0.41	1	8
PI3K	0.053	0.037	-10000	0	-0.33	2	2
EFNA5	-0.022	0.16	-10000	0	-0.6	37	37
Ephrin B2/EPHB4	0.034	0.013	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	0.029	0.048	-10000	0	-0.37	1	1
CDC42	0.028	0.006	-10000	0	-10000	0	0
RAS family/GTP	0.016	0.055	-10000	0	-0.5	2	2
PTK2	0.02	0.087	0.53	14	-10000	0	14
MAP4K4	0.022	0.062	0.36	5	-0.54	2	7
SRC	0.028	0.006	-10000	0	-10000	0	0
KALRN	0.027	0.007	-10000	0	-10000	0	0
Intersectin/N-WASP	0.037	0.015	-10000	0	-10000	0	0
neuron projection morphogenesis	0.067	0.12	0.4	40	-0.44	1	41
MAP2K1	0.03	0.042	-10000	0	-0.4	1	1
WASL	0.026	0.009	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	0.059	0.063	-10000	0	-0.44	5	5
cell migration	0.042	0.08	0.42	6	-0.43	1	7
NRAS	0.028	0.005	-10000	0	-10000	0	0
SYNJ1	0.018	0.053	-10000	0	-10000	0	0
PXN	0.028	0.005	-10000	0	-10000	0	0
TF	-0.046	0.12	-10000	0	-0.54	2	2
HRAS/GTP	0.042	0.067	-10000	0	-0.49	3	3
Ephrin B1/EPHB1-2	0.043	0.058	-10000	0	-0.47	4	4
cell adhesion mediated by integrin	-0.002	0.058	0.35	6	-0.38	3	9
RAC1	0.026	0.009	-10000	0	-10000	0	0
mol:GTP	0.046	0.068	-10000	0	-0.51	2	2
RAC1-CDC42/GTP	0.004	0.069	-10000	0	-0.66	2	2
RASA1	0.024	0.03	-10000	0	-0.61	1	1
RAC1-CDC42/GDP	0.045	0.06	0.35	2	-0.39	1	3
ruffle organization	0.068	0.13	0.4	47	-0.54	1	48
NCK1	0.026	0.029	-10000	0	-0.61	1	1
receptor internalization	0.008	0.059	-10000	0	-10000	0	0
Ephrin B/EPHB2/KALRN	0.067	0.063	-10000	0	-10000	0	0
ROCK1	0.018	0.06	-10000	0	-0.35	11	11
RAS family/GDP	-0.007	0.043	-10000	0	-0.38	2	2
Rac1/GTP	0.011	0.054	-10000	0	-0.48	2	2
Ephrin B/EPHB1/Src/Paxillin	0.032	0.041	-10000	0	-0.34	1	1

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.037	0.009	-10000	0	-10000	0	0
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0.028	0.005	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.024	0.049	-10000	0	-0.61	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.028	0.005	-10000	0	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.019	0.026	-10000	0	-0.22	1	1
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.028	0.004	-10000	0	-10000	0	0
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	0.028	0.005	-10000	0	-10000	0	0
FYN	0.027	0.008	-10000	0	-10000	0	0
MAP3K12	0.027	0.029	-10000	0	-0.61	1	1
FGR	0.025	0.041	-10000	0	-0.5	3	3
p38 alpha/TAB1	-0.021	0.081	-10000	0	-0.5	10	10
PRKG1	0.013	0.097	-10000	0	-0.61	12	12
DUSP8	0.027	0.028	-10000	0	-0.61	1	1
PGK/cGMP/p38 alpha	0.025	0.1	-10000	0	-0.52	10	10
apoptosis	-0.02	0.076	-10000	0	-0.47	10	10
RAL/GTP	0.034	0.013	-10000	0	-10000	0	0
LYN	0.027	0.007	-10000	0	-10000	0	0
DUSP1	0.02	0.026	-10000	0	-0.5	1	1
PAK1	0.029	0.003	-10000	0	-10000	0	0
SRC	0.028	0.006	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.064	0.026	-10000	0	-10000	0	0
TRAF6	0.029	0.003	-10000	0	-10000	0	0
RAC1	0.026	0.009	-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	0.026	0.009	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0.034	0.014	-10000	0	-10000	0	0
MAPK11	0.041	0.11	0.34	16	-0.44	8	24
BLK	-0.009	0.13	-10000	0	-0.5	33	33
HCK	0.001	0.12	-10000	0	-0.5	26	26
MAP2K3	0.028	0.005	-10000	0	-10000	0	0
DUSP16	0.028	0.005	-10000	0	-10000	0	0
DUSP10	0.024	0.044	-10000	0	-0.54	3	3
TRAF6/MEKK3	0.036	0.007	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.036	0.12	0.3	14	-0.62	8	22
positive regulation of innate immune response	0.047	0.13	0.36	17	-0.64	7	24
LCK	0.004	0.11	-10000	0	-0.51	22	22
p38alpha-beta/MKP7	0.05	0.12	0.32	9	-0.64	6	15
p38alpha-beta/MKP5	0.053	0.13	0.39	13	-0.59	8	21
PGK/cGMP	0.009	0.072	-10000	0	-0.45	12	12
PAK2	0.027	0.006	-10000	0	-10000	0	0
p38alpha-beta/MKP1	0.032	0.11	0.42	4	-0.6	7	11
CDC42	0.028	0.006	-10000	0	-10000	0	0
RALB	0.028	0.005	-10000	0	-10000	0	0
RALA	0.026	0.009	-10000	0	-10000	0	0
PAK3	0.014	0.088	-10000	0	-0.53	13	13

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	0.015	0.089	-10000	0	-0.58	11	11
CLTC	0.015	0.088	-10000	0	-0.34	23	23
calcium ion-dependent exocytosis	0.025	0.028	0.2	1	-10000	0	1
Dynamin 2/GTP	0.03	0.01	-10000	0	-10000	0	0
EXOC4	0.026	0.009	-10000	0	-10000	0	0
CD59	0.012	0.067	-10000	0	-0.28	21	21
CPE	0.005	0.065	-10000	0	-0.31	21	21
CTNNB1	0.02	0.013	-10000	0	-10000	0	0
membrane fusion	0.017	0.015	-10000	0	-10000	0	0
CTNND1	0.023	0.021	-10000	0	-10000	0	0
DNM2	0.029	0.003	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.02	0.05	0.26	1	-0.45	1	2
TSHR	-0.019	0.1	-10000	0	-0.31	58	58
INS	0.015	0.039	-10000	0	-0.77	1	1
BIN1	0.028	0.005	-10000	0	-10000	0	0
mol:Choline	0.017	0.015	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.018	0.006	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.027	0.008	-10000	0	-10000	0	0
mol:Ca2+	0.03	0.01	-10000	0	-10000	0	0
JUP	0.01	0.07	-10000	0	-0.32	5	5
ASAP2/amphiphysin II	0.05	0.017	-10000	0	-10000	0	0
ARF6/GTP	0.02	0.006	-10000	0	-10000	0	0
CDH1	0.006	0.079	-10000	0	-0.31	20	20
clathrin-independent pinocytosis	0.02	0.006	-10000	0	-10000	0	0
MAPK8IP3	-0.01	0.14	-10000	0	-0.5	36	36
positive regulation of endocytosis	0.02	0.006	-10000	0	-10000	0	0
EXOC2	0.028	0.005	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.031	0.027	-10000	0	-0.29	1	1
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.028	0.005	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.018	0.078	0.42	3	-10000	0	3
positive regulation of phagocytosis	0.018	0.006	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.011	0.088	-10000	0	-0.3	36	36
ACAP1	0.014	0.033	-10000	0	-0.26	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.005	0.064	-10000	0	-0.29	22	22
clathrin heavy chain/ACAP1	0.019	0.071	-10000	0	-0.33	5	5
JIP4/KLC1	0.05	0.017	-10000	0	-10000	0	0
EXOC1	0.028	0.004	-10000	0	-10000	0	0
exocyst	0.032	0.027	-10000	0	-0.3	1	1
RALA/GTP	0.019	0.007	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.035	0.012	-10000	0	-10000	0	0
receptor recycling	0.02	0.006	-10000	0	-10000	0	0
CTNNA1	0.019	0.023	-10000	0	-10000	0	0
NME1	0.018	0.006	-10000	0	-10000	0	0
clathrin coat assembly	0.014	0.091	-10000	0	-0.34	23	23
IL2RA	-0.016	0.086	-10000	0	-0.3	22	22
VAMP3	0.018	0.006	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	0.02	0.08	-10000	0	-0.41	4	4
EXOC6	0.028	0.006	-10000	0	-10000	0	0
PLD1	0.019	0.009	-10000	0	-10000	0	0
PLD2	0.019	0.009	-10000	0	-10000	0	0
EXOC5	0.027	0.008	-10000	0	-10000	0	0
PIP5K1C	0.02	0.048	0.2	1	-0.46	1	2
SDC1	0.009	0.076	-10000	0	-0.3	22	22
ARF6/GDP	0.027	0.009	-10000	0	-10000	0	0
EXOC7	0.028	0.005	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.02	0.081	-10000	0	-0.43	3	3
mol:Phosphatidic acid	0.017	0.015	-10000	0	-10000	0	0
endocytosis	-0.048	0.016	-10000	0	-10000	0	0
SCAMP2	0.029	0.003	-10000	0	-10000	0	0
ADRB2	0.059	0.11	0.33	6	-0.38	4	10
EXOC3	0.026	0.009	-10000	0	-10000	0	0
ASAP2	0.028	0.005	-10000	0	-10000	0	0
Dynamin 2/GDP	0.034	0.011	-10000	0	-10000	0	0
KLC1	0.027	0.008	-10000	0	-10000	0	0
AVPR2	-0.11	0.19	0.3	1	-0.56	26	27
RALA	0.026	0.009	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.035	0.081	-10000	0	-0.49	1	1

PDGFR-beta 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
S1P1/Sphingosine-1-phosphate	0.014	0.069	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SLAP	0.013	0.085	-10000	0	-0.37	23	23
PDGFB-D/PDGFRB/APS/CBL	0.039	0.04	-10000	0	-0.33	3	3
AKT1	0.081	0.13	0.38	57	-10000	0	57
mol:PI-4-5-P2	0	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.043	0.09	0.34	6	-10000	0	6
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
FGR	0.036	0.1	0.33	6	-0.63	2	8
mol:Ca2+	0.047	0.064	0.33	8	-10000	0	8
MYC	0.062	0.12	0.46	18	-10000	0	18
SHC1	0.027	0.006	-10000	0	-10000	0	0
HRAS/GDP	0.05	0.055	-10000	0	-0.56	1	1
LRP1/PDGFRB/PDGFB	0.044	0.026	-10000	0	-10000	0	0
GRB10	0.026	0.009	-10000	0	-10000	0	0
PTPN11	0.028	0.005	-10000	0	-10000	0	0
GO:0007205	0.047	0.064	0.33	8	-10000	0	8
PTEN	0.028	0.006	-10000	0	-10000	0	0
GRB2	0.028	0.005	-10000	0	-10000	0	0
GRB7	0.021	0.069	-10000	0	-0.61	6	6
PDGFB-D/PDGFRB/SHP2	0.032	0.019	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB10	0.031	0.02	-10000	0	-10000	0	0
cell cycle arrest	0.013	0.085	-10000	0	-0.36	23	23
HRAS	0.028	0.024	-10000	0	-0.5	1	1
HIF1A	0.072	0.13	0.37	55	-0.51	1	56
GAB1	0.045	0.078	0.34	8	-10000	0	8
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	0.045	0.082	0.34	12	-10000	0	12
PDGFB-D/PDGFRB	0.043	0.027	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.032	0.019	-10000	0	-10000	0	0
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.011	0.069	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	0.032	0.019	-10000	0	-10000	0	0
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
mol:IP3	0.047	0.064	0.33	8	-10000	0	8
E5	0	0.001	-10000	0	-10000	0	0
CSK	0.027	0.005	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7	0.027	0.053	-10000	0	-0.46	5	5
SHB	0.028	0.006	-10000	0	-10000	0	0
BLK	0.014	0.12	0.32	4	-0.48	8	12
PTPN2	0.03	0.006	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.033	0.019	-10000	0	-10000	0	0
BCAR1	0.027	0.029	-10000	0	-0.61	1	1
VAV2	0.047	0.086	0.36	10	-10000	0	10
CBL	0.027	0.028	-10000	0	-0.61	1	1
PDGFB-D/PDGFRB/DEP1	0.033	0.019	-10000	0	-10000	0	0
LCK	0.03	0.11	0.32	7	-0.46	9	16
PDGFRB	0.022	0.013	-10000	0	-10000	0	0
ACP1	0.028	0.005	-10000	0	-10000	0	0
HCK	0.044	0.076	0.34	5	-10000	0	5
ABL1	0.047	0.087	0.33	12	-0.45	2	14
PDGFB-D/PDGFRB/CBL	0.04	0.072	0.34	4	-0.41	2	6
PTPN1	0.029	0.006	-10000	0	-10000	0	0
SNX15	0.029	0.003	-10000	0	-10000	0	0
STAT3	0.028	0.004	-10000	0	-10000	0	0
STAT1	0.026	0.024	-10000	0	-0.5	1	1
cell proliferation	0.061	0.12	0.42	22	-10000	0	22
SLA	0.002	0.11	-10000	0	-0.5	24	24
actin cytoskeleton reorganization	0.036	0.044	0.35	2	-10000	0	2
SRC	0.049	0.064	0.32	4	-10000	0	4
PI3K	0.01	0.025	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	0.038	0.049	-10000	0	-0.39	4	4
SH2B2	0.023	0.041	-10000	0	-0.5	3	3
PLCgamma1/SPHK1	0.043	0.091	0.34	6	-10000	0	6
LYN	0.039	0.091	0.32	4	-0.55	3	7
LRP1	0.028	0.005	-10000	0	-10000	0	0
SOS1	0.028	0.005	-10000	0	-10000	0	0
STAT5B	0.028	0.004	-10000	0	-10000	0	0
STAT5A	0.028	0.004	-10000	0	-10000	0	0
NCK1-2/p130 Cas	0.059	0.048	-10000	0	-10000	0	0
SPHK1	-0.012	0.14	-10000	0	-0.5	40	40
EDG1	0.001	0.003	-10000	0	-10000	0	0
mol:DAG	0.047	0.064	0.33	8	-10000	0	8
PLCG1	0.048	0.065	0.34	8	-10000	0	8
NHERF/PDGFRB	0.042	0.032	-10000	0	-0.39	1	1
YES1	0.047	0.074	0.32	3	-0.56	2	5
cell migration	0.042	0.032	-10000	0	-0.39	1	1
SHC/Grb2/SOS1	0.061	0.042	-10000	0	-10000	0	0
SLC9A3R2	0.026	0.029	-10000	0	-0.61	1	1
SLC9A3R1	0.028	0.005	-10000	0	-10000	0	0
NHERF1-2/PDGFRB/PTEN	0.051	0.039	-10000	0	-0.35	1	1
FYN	0.028	0.11	0.31	5	-0.41	11	16
DOK1	0.057	0.064	-10000	0	-10000	0	0
HRAS/GTP	0.02	0.017	-10000	0	-0.36	1	1
PDGFB	0.028	0.004	-10000	0	-10000	0	0
RAC1	0.064	0.11	0.45	14	-10000	0	14
PRKCD	0.036	0.056	-10000	0	-10000	0	0
FER	0.032	0.051	-10000	0	-0.36	2	2
MAPKKK cascade	0.04	0.083	0.37	15	-10000	0	15
RASA1	0.043	0.058	-10000	0	-0.36	1	1
NCK1	0.026	0.029	-10000	0	-0.61	1	1
NCK2	0.028	0.005	-10000	0	-10000	0	0
p62DOK/Csk	0.072	0.06	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SHB	0.031	0.019	-10000	0	-10000	0	0
chemotaxis	0.047	0.086	0.33	12	-0.44	2	14
STAT1-3-5/STAT1-3-5	0.05	0.036	-10000	0	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0.016	0.01	-10000	0	-10000	0	0
PTPRJ	0.029	0.003	-10000	0	-10000	0	0

Class IB PI3K non-lipid kinase 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
cAMP biosynthetic process	-0.023	0.059	0.57	5	-10000	0	5
PI3K Class IB/PDE3B	0.023	0.059	-10000	0	-0.57	5	5
PDE3B	0.023	0.059	-10000	0	-0.57	5	5

p38 MAPK signaling pathway

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
TRAF6/ASK1	0.023	0.008	-10000	0	-10000	0	0
TRAF2/ASK1	0.035	0.012	-10000	0	-10000	0	0
ATM	0.027	0.028	-10000	0	-0.61	1	1
MAP2K3	0.03	0.069	0.47	3	-0.31	2	5
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.031	0.072	0.41	3	-0.33	6	9
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.018	0.072	-10000	0	-0.52	9	9
TXN	0.009	0.002	-10000	0	-10000	0	0
CALM1	0.027	0.008	-10000	0	-10000	0	0
GADD45A	0.028	0.006	-10000	0	-10000	0	0
GADD45B	0.029	0.003	-10000	0	-10000	0	0
MAP3K1	0.026	0.008	-10000	0	-10000	0	0
MAP3K6	0.026	0.029	-10000	0	-0.61	1	1
MAP3K7	0.027	0.007	-10000	0	-10000	0	0
MAP3K4	0.026	0.008	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.038	0.025	-10000	0	-0.45	1	1
TAK1/TAB family	-0.004	0.013	-10000	0	-10000	0	0
RAC1/OSM/MEKK3	0.049	0.019	-10000	0	-10000	0	0
TRAF2	0.028	0.005	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.035	0.051	-10000	0	-10000	0	0
TRAF6	0.01	0.001	-10000	0	-10000	0	0
RAC1	0.026	0.009	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.062	0.22	-10000	0	-0.6	71	71
CCM2	0.026	0.009	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.025	0.14	-10000	0	-0.38	71	71
MAPK11	0.027	0.024	-10000	0	-0.5	1	1
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.01	0.14	-10000	0	-0.34	71	71
OSM/MEKK3	0.037	0.014	-10000	0	-10000	0	0
TAOK1	0.014	0.041	-10000	0	-0.33	7	7
TAOK2	0.018	0.017	-10000	0	-0.36	1	1
TAOK3	0.018	0.017	-10000	0	-0.36	1	1
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.028	0.006	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.027	0.008	-10000	0	-10000	0	0
MAP3K10	0.027	0.028	-10000	0	-0.61	1	1
MAP3K3	0.028	0.005	-10000	0	-10000	0	0
TRX/ASK1	0.024	0.018	-10000	0	-10000	0	0
GADD45/MTK1/MTK1	0.055	0.047	-10000	0	-0.3	1	1

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	0.041	0.11	0.38	2	-0.57	9	11
MAP3K8	0.026	0.034	-10000	0	-0.5	2	2
FOS	0.028	0.099	0.35	4	-0.53	8	12
PRKCA	0.028	0.008	-10000	0	-10000	0	0
PTPN7	-0.006	0.13	-10000	0	-0.51	33	33
HRAS	0.028	0.024	-10000	0	-0.5	1	1
PRKCB	0.022	0.058	-10000	0	-0.56	5	5
NRAS	0.028	0.006	-10000	0	-10000	0	0
RAS family/GTP	0.052	0.022	-10000	0	-0.28	1	1
MAPK3	0.016	0.085	-10000	0	-0.5	9	9
MAP2K1	0.026	0.051	-10000	0	-0.48	2	2
ELK1	0.028	0.009	-10000	0	-10000	0	0
BRAF	0.026	0.037	-10000	0	-0.44	2	2
mol:GTP	0	0.002	-10000	0	-0.007	13	13
MAPK1	0.016	0.087	-10000	0	-0.54	7	7
RAF1	0.019	0.038	-10000	0	-0.44	2	2
KRAS	0.028	0.006	-10000	0	-10000	0	0

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	0.01	0.035	-10000	0	-0.39	4	4
SNTA1	0.026	0.029	-10000	0	-0.61	1	1
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	0.01	0.035	-10000	0	-0.38	4	4
MAPK12	0.007	0.044	-10000	0	-0.29	11	11
CCND1	0.012	0.042	-10000	0	-0.29	4	4
p38 gamma/SNTA1	0.03	0.061	0.28	2	-0.42	3	5
MAP2K3	0.028	0.005	-10000	0	-10000	0	0
PKN1	0.029	0.002	-10000	0	-10000	0	0
G2/M transition checkpoint	0.012	0.053	0.21	11	-0.28	11	22
MAP2K6	0.013	0.03	-10000	0	-0.37	3	3
MAPT	0.015	0.064	0.31	4	-0.39	8	12
MAPK13	0.016	0.042	-10000	0	-0.45	4	4
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.019	0.007	-10000	0	-10000	0	0

IGF1 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
NCK2	0.028	0.005	-10000	0	-10000	0	0
PTK2	0.027	0.006	-10000	0	-10000	0	0
CRKL	0.023	0.035	-10000	0	-10000	0	0
GRB2/SOS1/SHC	0.054	0.016	-10000	0	-10000	0	0
HRAS	0.028	0.024	-10000	0	-0.5	1	1
IRS1/Crk	0.028	0.032	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/PTP1B	0.051	0.037	-10000	0	-10000	0	0
AKT1	0.032	0.067	0.31	6	-0.58	1	7
BAD	0.027	0.07	0.3	6	-0.75	1	7
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.023	0.033	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.033	0.034	-10000	0	-10000	0	0
RAF1	-0.054	0.18	0.31	5	-0.4	95	100
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.062	0.039	-10000	0	-10000	0	0
YWHAZ	0.027	0.007	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.032	0.035	-10000	0	-0.24	6	6
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
RPS6KB1	0.037	0.07	0.32	7	-0.58	1	8
GNB2L1	0.022	0.012	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.048	0.16	0.31	10	-0.43	4	14
PXN	0.028	0.005	-10000	0	-10000	0	0
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.041	0.009	-10000	0	-10000	0	0
HRAS/GTP	0.03	0.031	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.075	0.038	-10000	0	-10000	0	0
IGF-1R heterotetramer	0.031	0.015	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	0.048	0.037	-10000	0	-10000	0	0
Crk/p130 Cas/Paxillin	0.062	0.043	-10000	0	-0.31	1	1
IGF1R	0.031	0.015	-10000	0	-10000	0	0
IGF1	0.025	0.052	-10000	0	-0.48	5	5
IRS2/Crk	0.03	0.047	-10000	0	-0.32	1	1
PI3K	0.056	0.049	-10000	0	-0.3	2	2
apoptosis	-0.043	0.07	0.62	1	-0.29	13	14
HRAS/GDP	0.02	0.017	-10000	0	-0.36	1	1
PRKCD	0.026	0.045	-10000	0	-0.55	1	1
RAF1/14-3-3 E	-0.045	0.18	0.32	8	-0.44	5	13
BAD/14-3-3	0.045	0.074	0.3	13	-0.68	1	14
PRKCZ	0.033	0.069	0.32	5	-0.58	1	6
Crk/p130 Cas/Paxillin/FAK1	0.038	0.044	-10000	0	-0.49	1	1
PTPN1	0.028	0.006	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.022	0.036	-10000	0	-0.32	3	3
BCAR1	0.027	0.029	-10000	0	-0.61	1	1
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.058	0.04	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.028	0.005	-10000	0	-10000	0	0
IRS1/NCK2	0.036	0.036	-10000	0	-10000	0	0
GRB10	0.026	0.009	-10000	0	-10000	0	0
PTPN11	0.023	0.036	-10000	0	-10000	0	0
IRS1	0.021	0.038	0.22	1	-0.26	4	5
IRS2	0.019	0.05	-10000	0	-0.28	6	6
IGF-1R heterotetramer/IGF1	0.038	0.043	-10000	0	-0.33	5	5
GRB2	0.028	0.005	-10000	0	-10000	0	0
PDPK1	0.04	0.07	0.31	7	-0.61	1	8
YWHAE	0.028	0.005	-10000	0	-10000	0	0
PRKD1	0.038	0.048	-10000	0	-0.43	1	1
SHC1	0.027	0.006	-10000	0	-10000	0	0

Insulin Pathway

Figure S111. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S111. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	0.043	0.051	-10000	0	-10000	0	0
TC10/GTP	0.043	0.038	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	0.062	0.044	-10000	0	-0.37	4	4
HRAS	0.028	0.024	-10000	0	-0.5	1	1
APS homodimer	0.023	0.041	-10000	0	-0.5	3	3
GRB14	-0.006	0.14	-10000	0	-0.61	27	27
FOXO3	-0.002	0.14	-10000	0	-0.61	26	26
AKT1	0.03	0.11	0.4	16	-0.55	2	18
INSR	0.032	0.008	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.062	0.018	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.026	0.009	-10000	0	-10000	0	0
SORBS1	0.026	0.029	-10000	0	-0.61	1	1
CRK	0.028	0.005	-10000	0	-10000	0	0
PTPN1	0.018	0.01	-10000	0	-10000	0	0
CAV1	0	0.077	0.24	1	-0.34	4	5
CBL/APS/CAP/Crk-II/C3G	0.068	0.049	-10000	0	-0.33	2	2
Insulin Receptor/Insulin/IRS1/NCK2	0.063	0.044	-10000	0	-0.37	4	4
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.044	0.045	-10000	0	-0.32	6	6
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.04	0.038	-10000	0	-10000	0	0
RPS6KB1	0.023	0.1	0.38	14	-0.5	2	16
PARD6A	0.024	0.049	-10000	0	-0.61	3	3
CBL	0.027	0.028	-10000	0	-0.61	1	1
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.015	0.057	-10000	0	-0.5	6	6
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
Insulin Receptor/Insuli/IRS1/GRB2/Shc	0.034	0.081	-10000	0	-0.51	2	2
HRAS/GTP	0.016	0.04	-10000	0	-0.5	1	1
Insulin Receptor	0.032	0.008	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.072	0.046	-10000	0	-0.34	4	4
PRKCI	0.029	0.051	-10000	0	-0.47	2	2
Insulin Receptor/Insulin/GRB14/PDK1	0.012	0.081	-10000	0	-0.6	2	2
SHC1	0.027	0.006	-10000	0	-10000	0	0
negative regulation of MAPKKK cascade	0.036	0.063	-10000	0	-0.45	7	7
PI3K	0.054	0.049	-10000	0	-0.32	6	6
NCK2	0.028	0.005	-10000	0	-10000	0	0
RHOQ	0.028	0.005	-10000	0	-10000	0	0
mol:H2O2	0	0.002	-10000	0	-10000	0	0
HRAS/GDP	0.02	0.017	-10000	0	-0.36	1	1
AKT2	0.036	0.12	0.41	20	-0.55	2	22
PRKCZ	0.023	0.075	-10000	0	-0.58	5	5
SH2B2	0.023	0.041	-10000	0	-0.5	3	3
SHC/SHIP	0.031	0.047	-10000	0	-0.38	4	4
F2RL2	-0.001	0.12	-10000	0	-0.5	26	26
TRIP10	0.029	0.003	-10000	0	-10000	0	0
Insulin Receptor/Insulin/Shc	0.05	0.015	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.037	0.008	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.077	0.026	-10000	0	-10000	0	0
RAPGEF1	0.028	0.005	-10000	0	-10000	0	0
RASA1	0.024	0.03	-10000	0	-0.61	1	1
NCK1	0.026	0.029	-10000	0	-0.61	1	1
CBL/APS/CAP/Crk-II	0.06	0.046	-10000	0	-0.35	2	2
TC10/GDP	0.021	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.061	0.026	-10000	0	-10000	0	0
INPP5D	0.016	0.048	-10000	0	-0.4	4	4
SOS1	0.028	0.005	-10000	0	-10000	0	0
SGK1	-0.033	0.17	-10000	0	-0.62	39	39
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.028	0.005	-10000	0	-10000	0	0
IRS1	0.022	0.057	-10000	0	-0.61	4	4
p62DOK/RasGAP	0.036	0.064	-10000	0	-0.46	7	7
INS	0.023	0.007	-10000	0	-10000	0	0
mol:PI-3-4-P2	0.016	0.047	-10000	0	-0.4	4	4
GRB2	0.028	0.005	-10000	0	-10000	0	0
EIF4EBP1	0.01	0.12	0.39	13	-0.53	5	18
PTPRA	0.03	0.006	-10000	0	-10000	0	0
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
TC10/GTP/CIP4	0.037	0.008	-10000	0	-10000	0	0
PDPK1	0.026	0.029	-10000	0	-0.61	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.033	0.03	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.046	0.04	-10000	0	-0.37	4	4
Insulin Receptor/Insulin/IRS3	0.04	0.011	-10000	0	-10000	0	0
Par3/Par6	0.04	0.078	-10000	0	-0.33	3	3

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.037	0.035	-10000	0	-0.45	2	2
ATM	0.027	0.028	-10000	0	-0.61	1	1
UBE2D3	0.028	0.004	-10000	0	-10000	0	0
PRKDC	0.027	0.007	-10000	0	-10000	0	0
ATR	0.027	0.007	-10000	0	-10000	0	0
UBE2L3	0.028	0.004	-10000	0	-10000	0	0
FANCD2	0.019	0.021	-10000	0	-0.35	1	1
protein ubiquitination	0.066	0.053	-10000	0	-0.45	2	2
XRCC5	0.027	0.007	-10000	0	-10000	0	0
XRCC6	0.028	0.004	-10000	0	-10000	0	0
M/R/N Complex	0.042	0.026	-10000	0	-10000	0	0
MRE11A	0.028	0.004	-10000	0	-10000	0	0
DNA-PK	0.052	0.019	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	-0.009	0.11	-10000	0	-0.56	14	14
FANCF	0.028	0.004	-10000	0	-10000	0	0
BRCA1	0.028	0.004	-10000	0	-10000	0	0
CCNE1	0.022	0.057	-10000	0	-0.5	6	6
CDK2/Cyclin E1	0.037	0.044	-10000	0	-0.36	6	6
FANCG	0.028	0.006	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.037	0.036	-10000	0	-0.45	2	2
FANCE	0.027	0.024	-10000	0	-0.5	1	1
FANCC	0.028	0.006	-10000	0	-10000	0	0
NBN	0.027	0.007	-10000	0	-10000	0	0
FANCA	-0.081	0.21	-10000	0	-0.5	104	104
DNA repair	0.012	0.099	0.37	6	-0.62	3	9
BRCA1/BARD1/ubiquitin	0.037	0.036	-10000	0	-0.45	2	2
BARD1/DNA-PK	0.063	0.038	-10000	0	-0.35	2	2
FANCL	0.028	0.005	-10000	0	-10000	0	0
mRNA polyadenylation	-0.037	0.035	0.45	2	-10000	0	2
BRCA1/BARD1/CTIP/M/R/N Complex	0.024	0.044	-10000	0	-0.67	1	1
BRCA1/BACH1/BARD1/TopBP1	0.05	0.035	-10000	0	-0.39	2	2
BRCA1/BARD1/P53	0.063	0.038	-10000	0	-0.35	2	2
BARD1/CSTF1/BRCA1	0.051	0.034	-10000	0	-0.39	2	2
BRCA1/BACH1	0.028	0.004	-10000	0	-10000	0	0
BARD1	0.024	0.045	-10000	0	-0.46	4	4
PCNA	0.028	0.005	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	0.052	0.034	-10000	0	-0.39	2	2
BRCA1/BARD1/UbcH7	0.052	0.034	-10000	0	-0.39	2	2
BRCA1/BARD1/RAD51/PCNA	0.056	0.066	-10000	0	-0.36	3	3
BARD1/DNA-PK/P53	0.073	0.04	-10000	0	-0.33	2	2
BRCA1/BARD1/Ubiquitin	0.037	0.036	-10000	0	-0.45	2	2
BRCA1/BARD1/CTIP	0.045	0.045	-10000	0	-0.46	3	3
FA complex	0.001	0.081	-10000	0	-0.42	5	5
BARD1/EWS	0.037	0.036	-10000	0	-0.45	2	2
RBBP8	0.019	0.037	-10000	0	-0.82	1	1
TP53	0.028	0.005	-10000	0	-10000	0	0
TOPBP1	0.027	0.007	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.061	0.037	0.35	2	-10000	0	2
BRCA1/BARD1	0.072	0.055	-10000	0	-0.58	1	1
CSTF1	0.028	0.006	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.018	0.033	-10000	0	-0.45	2	2
CDK2	0.028	0.005	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.014	0.089	-10000	0	-0.51	14	14
RAD50	0.022	0.012	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.037	0.036	-10000	0	-0.45	2	2
EWSR1	0.028	0.004	-10000	0	-10000	0	0

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.028	0.006	-10000	0	-10000	0	0
HDAC2	0.027	0.007	-10000	0	-10000	0	0
GNB1/GNG2	0.047	0.03	-10000	0	-0.39	1	1
forebrain development	0.041	0.11	0.45	6	-0.46	7	13
GNAO1	0.024	0.05	-10000	0	-0.53	4	4
SMO/beta Arrestin2	0.037	0.035	-10000	0	-0.46	2	2
SMO	0.025	0.03	-10000	0	-0.61	1	1
ARRB2	0.027	0.029	-10000	0	-0.62	1	1
GLI3/SPOP	0.051	0.091	0.27	1	-0.51	8	9
mol:GTP	0	0.002	-10000	0	-10000	0	0
GSK3B	0.027	0.008	-10000	0	-10000	0	0
GNAI2	0.021	0.014	-10000	0	-10000	0	0
SIN3/HDAC complex	0.058	0.064	-10000	0	-10000	0	0
GNAI1	0.025	0.03	-10000	0	-0.61	1	1
XPO1	0.029	0.011	-10000	0	-10000	0	0
GLI1/Su(fu)	0.034	0.093	-10000	0	-0.56	5	5
SAP30	0.01	0.096	-10000	0	-0.5	17	17
mol:GDP	0.025	0.03	-10000	0	-0.61	1	1
MIM/GLI2A	0.026	0.03	-10000	0	-10000	0	0
IFT88	0.027	0.029	-10000	0	-0.61	1	1
GNAI3	0.028	0.006	-10000	0	-10000	0	0
GLI2	0.067	0.081	0.3	12	-0.47	1	13
GLI3	0.038	0.097	0.3	3	-0.57	8	11
CSNK1D	0.028	0.005	-10000	0	-10000	0	0
CSNK1E	0.028	0.004	-10000	0	-10000	0	0
SAP18	0.028	0.005	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.027	0.029	-10000	0	-0.61	1	1
GNG2	0.027	0.008	-10000	0	-10000	0	0
Gi family/GTP	0.021	0.045	-10000	0	-0.35	4	4
SIN3B	0.029	0.003	-10000	0	-10000	0	0
SIN3A	0.029	0.003	-10000	0	-10000	0	0
GLI3/Su(fu)	0.04	0.1	-10000	0	-0.57	10	10
GLI2/Su(fu)	0.066	0.068	0.26	2	-0.47	2	4
FOXA2	-0.005	0.2	-10000	0	-0.98	15	15
neural tube patterning	0.041	0.11	0.45	6	-0.46	7	13
SPOP	0.028	0.005	-10000	0	-10000	0	0
Su(fu)/PIAS1	0.042	0.048	-10000	0	-0.48	1	1
GNB1	0.028	0.006	-10000	0	-10000	0	0
CSNK1G2	0.027	0.029	-10000	0	-0.61	1	1
CSNK1G3	0.022	0.012	-10000	0	-10000	0	0
MTSS1	0.026	0.03	-10000	0	-10000	0	0
embryonic limb morphogenesis	0.041	0.11	0.45	6	-0.46	7	13
SUFU	0.027	0.03	-10000	0	-0.53	1	1
LGALS3	0.016	0.076	-10000	0	-0.52	10	10
catabolic process	0.097	0.12	0.34	16	-0.55	7	23
GLI3A/CBP	0.029	0.041	-10000	0	-0.36	2	2
KIF3A	0.022	0.012	-10000	0	-10000	0	0
GLI1	0.041	0.11	0.47	5	-0.47	7	12
RAB23	0.028	0.006	-10000	0	-10000	0	0
CSNK1A1	0.022	0.012	-10000	0	-10000	0	0
IFT172	0.028	0.005	-10000	0	-10000	0	0
RBBP7	0.028	0.003	-10000	0	-10000	0	0
Su(fu)/Galectin3	0.034	0.072	-10000	0	-0.45	6	6
GNAZ	0.025	0.049	-10000	0	-0.61	3	3
RBBP4	0.026	0.029	-10000	0	-0.61	1	1
CSNK1G1	0.029	0.003	-10000	0	-10000	0	0
PIAS1	0.029	0.003	-10000	0	-10000	0	0
PRKACA	0.029	0.002	-10000	0	-10000	0	0
GLI2/SPOP	0.079	0.067	0.27	11	-10000	0	11
STK36	0.028	0.011	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.025	0.037	-10000	0	-0.36	2	2
PTCH1	0.041	0.11	0.47	5	-0.96	1	6
MIM/GLI1	0.043	0.14	0.45	2	-0.49	13	15
CREBBP	0.029	0.041	-10000	0	-0.35	2	2
Su(fu)/SIN3/HDAC complex	0.026	0.1	0.25	1	-0.5	12	13

Class I PI3K signaling events mediated by Akt

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
BCL2L1	0.02	0.004	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.047	0.027	-10000	0	-0.35	1	1
CDKN1B	0.015	0.078	-10000	0	-0.58	1	1
CDKN1A	0.014	0.076	-10000	0	-0.59	2	2
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.027	0.007	-10000	0	-10000	0	0
FOXO3	0.015	0.072	-10000	0	-0.59	2	2
AKT1	0.016	0.057	-10000	0	-0.62	2	2
BAD	0.026	0.037	-10000	0	-0.56	2	2
AKT3	0.017	0.018	-10000	0	-0.36	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.012	0.082	-10000	0	-0.59	2	2
AKT1/ASK1	0.021	0.094	-10000	0	-0.51	4	4
BAD/YWHAZ	0.053	0.029	-10000	0	-0.35	2	2
RICTOR	0.026	0.009	-10000	0	-10000	0	0
RAF1	0.02	0.013	-10000	0	-10000	0	0
JNK cascade	-0.02	0.091	0.5	4	-10000	0	4
TSC1	0.016	0.068	-10000	0	-0.58	1	1
YWHAZ	0.027	0.007	-10000	0	-10000	0	0
AKT1/RAF1	0.015	0.094	-10000	0	-0.52	4	4
EP300	0.027	0.029	-10000	0	-0.61	1	1
mol:GDP	0.004	0.082	-10000	0	-0.36	9	9
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.009	0.081	-10000	0	-0.59	2	2
YWHAQ	0.028	0.005	-10000	0	-10000	0	0
TBC1D4	0.014	0.015	-10000	0	-0.31	1	1
MAP3K5	0.027	0.008	-10000	0	-10000	0	0
MAPKAP1	0.028	0.006	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.028	0.083	0.33	8	-0.25	9	17
YWHAH	0.028	0.004	-10000	0	-10000	0	0
AKT1S1	0.012	0.081	-10000	0	-0.59	2	2
CASP9	0.016	0.07	-10000	0	-0.6	1	1
YWHAB	0.028	0.006	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.028	0.096	0.34	5	-0.46	4	9
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.05	0.028	-10000	0	-0.39	1	1
YWHAE	0.028	0.005	-10000	0	-10000	0	0
SRC	0.028	0.006	-10000	0	-10000	0	0
AKT2/p21CIP1	0.011	0.079	-10000	0	-0.48	4	4
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.013	0.027	-10000	0	-10000	0	0
CHUK	0.013	0.078	-10000	0	-0.59	2	2
BAD/BCL-XL	0.032	0.095	-10000	0	-0.5	4	4
mTORC2	0.032	0.013	-10000	0	-10000	0	0
AKT2	0.018	0.017	-10000	0	-0.36	1	1
FOXO1-3a-4/14-3-3 family	0.03	0.11	0.32	7	-0.42	11	18
PDPK1	0.026	0.029	-10000	0	-0.61	1	1
MDM2	0.015	0.079	-10000	0	-0.58	1	1
MAPKKK cascade	-0.015	0.092	0.51	4	-10000	0	4
MDM2/Cbp/p300	0.041	0.096	0.32	3	-0.44	5	8
TSC1/TSC2	0.02	0.08	0.28	11	-0.57	2	13
proteasomal ubiquitin-dependent protein catabolic process	0.038	0.092	0.3	3	-0.42	5	8
glucose import	0.008	0.053	-10000	0	-0.34	7	7
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.021	0.054	0.24	3	-0.33	2	5
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	0.006	0.05	-10000	0	-0.34	7	7
GSK3A	0.012	0.081	-10000	0	-0.59	2	2
FOXO1	0.012	0.081	-10000	0	-0.59	2	2
GSK3B	0.014	0.075	-10000	0	-0.59	2	2
SFN	-0.036	0.18	-10000	0	-0.52	59	59
G1/S transition of mitotic cell cycle	0.018	0.081	0.34	3	-0.54	3	6
p27Kip1/14-3-3 family	0.036	0.066	0.29	1	-0.41	2	3
PRKACA	0.029	0.002	-10000	0	-10000	0	0
KPNA1	0.027	0.007	-10000	0	-10000	0	0
HSP90AA1	0.027	0.008	-10000	0	-10000	0	0
YWHAG	0.026	0.009	-10000	0	-10000	0	0
RHEB	0.026	0.009	-10000	0	-10000	0	0
CREBBP	0.028	0.006	-10000	0	-10000	0	0

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.022	0.012	-10000	0	-10000	0	0
alphaV beta3 Integrin	0.037	0.039	-10000	0	-0.45	3	3
PTK2	0.024	0.073	-10000	0	-0.4	1	1
positive regulation of JNK cascade	0.007	0.1	-10000	0	-0.35	14	14
CDC42/GDP	0.031	0.14	0.36	3	-0.45	11	14
Rac1/GDP	0.025	0.13	0.28	1	-0.45	10	11
RAP1B	0.028	0.005	-10000	0	-10000	0	0
RAP1A	0.028	0.005	-10000	0	-10000	0	0
CTNNB1	0.02	0.013	-10000	0	-10000	0	0
CDC42/GTP	0.016	0.13	-10000	0	-0.43	14	14
nectin-3/I-afadin	0.035	0.028	-10000	0	-0.45	1	1
RAPGEF1	0.014	0.12	0.3	2	-0.42	2	4
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.008	0.13	-10000	0	-0.48	2	2
PDGFB-D/PDGFRB	0.022	0.012	-10000	0	-10000	0	0
TLN1	0.013	0.012	-10000	0	-10000	0	0
Rap1/GTP	0.009	0.089	-10000	0	-10000	0	0
IQGAP1	0.029	0.003	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.049	0.019	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.035	0.028	-10000	0	-0.45	1	1
PVR	0.029	0.003	-10000	0	-10000	0	0
Necl-5(dimer)	0.028	0.003	-10000	0	-10000	0	0
mol:GDP	0.017	0.16	0.39	3	-0.52	17	20
MLLT4	0.026	0.008	-10000	0	-10000	0	0
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
PI3K	0.054	0.051	-10000	0	-0.34	2	2
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.039	0.013	-10000	0	-10000	0	0
positive regulation of lamellipodium assembly	0.011	0.1	-10000	0	-0.36	10	10
PVRL1	0.029	0.003	-10000	0	-10000	0	0
PVRL3	0.025	0.033	-10000	0	-0.46	2	2
PVRL2	0.029	0.003	-10000	0	-10000	0	0
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
CDH1	0.007	0.11	-10000	0	-0.59	17	17
CLDN1	0.022	0.059	-10000	0	-0.57	5	5
JAM-A/CLDN1	0.056	0.049	-10000	0	-0.35	4	4
SRC	0.004	0.14	-10000	0	-0.53	2	2
ITGB3	0.024	0.049	-10000	0	-0.61	3	3
nectin-1(dimer)/I-afadin/I-afadin	0.039	0.013	-10000	0	-10000	0	0
FARP2	0.01	0.17	-10000	0	-0.66	14	14
RAC1	0.026	0.009	-10000	0	-10000	0	0
CTNNA1	0.022	0.012	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.049	0.03	-10000	0	-0.39	1	1
nectin-1/I-afadin	0.039	0.013	-10000	0	-10000	0	0
nectin-2/I-afadin	0.039	0.013	-10000	0	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0.035	0.012	-10000	0	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.049	0.03	-10000	0	-0.39	1	1
CDC42/GTP/IQGAP1/filamentous actin	0.037	0.009	-10000	0	-10000	0	0
F11R	0.027	0.006	-10000	0	-10000	0	0
positive regulation of filopodium formation	0.007	0.1	-10000	0	-0.35	14	14
alphaV/beta3 Integrin/Talin	0.042	0.044	0.28	2	-10000	0	2
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.039	0.013	-10000	0	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.039	0.013	-10000	0	-10000	0	0
PIP5K1C	0.014	0.013	-10000	0	-10000	0	0
VAV2	0.012	0.17	-10000	0	-0.64	11	11
RAP1/GDP	0.031	0.12	-10000	0	-0.4	4	4
ITGAV	0.027	0.006	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.049	0.03	-10000	0	-0.39	1	1
nectin-3(dimer)/I-afadin/I-afadin	0.035	0.028	-10000	0	-0.45	1	1
Rac1/GTP	0.017	0.12	-10000	0	-0.46	9	9
PTPRM	0.017	0.015	-10000	0	-0.22	1	1
E-cadherin/beta catenin/alpha catenin	0.039	0.071	-10000	0	-10000	0	0
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.028	0.006	-10000	0	-10000	0	0

Osteopontin-mediated events

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
IKK alpha homodimer	0.054	0.056	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.07	0.076	0.36	5	-0.56	1	6
alphaV/beta3 Integrin/Osteopontin/Src	0.044	0.042	-10000	0	-0.45	3	3
AP1	0.08	0.092	-10000	0	-0.6	2	2
ILK	0.043	0.052	-10000	0	-10000	0	0
bone resorption	0.04	0.079	-10000	0	-0.54	2	2
PTK2B	0.026	0.009	-10000	0	-10000	0	0
PYK2/p130Cas	0.069	0.06	-10000	0	-10000	0	0
ITGAV	0.031	0.01	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.024	0.081	-10000	0	-0.37	20	20
alphaV/beta3 Integrin/Osteopontin	0.062	0.051	-10000	0	-0.37	5	5
MAP3K1	0.039	0.053	-10000	0	-10000	0	0
JUN	0.028	0.007	-10000	0	-10000	0	0
MAPK3	0.034	0.057	-10000	0	-10000	0	0
MAPK1	0.036	0.057	-10000	0	-10000	0	0
Rac1/GDP	0.019	0.007	-10000	0	-10000	0	0
NFKB1	0.027	0.029	-10000	0	-0.61	1	1
MAPK8	0.034	0.06	0.4	1	-0.62	1	2
ITGB3	0.028	0.049	-10000	0	-0.6	3	3
NFKBIA	0.034	0.055	-10000	0	-10000	0	0
FOS	0.012	0.096	-10000	0	-0.6	12	12
CD44	0.01	0.098	-10000	0	-0.5	18	18
CHUK	0.028	0.006	-10000	0	-10000	0	0
PLAU	0.042	0.16	0.51	4	-1.1	8	12
NF kappa B1 p50/RelA	0.077	0.072	0.37	1	-0.54	1	2
BCAR1	0.027	0.029	-10000	0	-0.61	1	1
RELA	0.029	0.003	-10000	0	-10000	0	0
alphaV beta3 Integrin	0.044	0.041	-10000	0	-0.44	3	3
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	0.041	0.056	-10000	0	-0.34	1	1
VAV3	0.025	0.078	-10000	0	-0.63	1	1
MAP3K14	0.042	0.058	-10000	0	-10000	0	0
ROCK2	0.025	0.043	-10000	0	-0.51	3	3
SPP1	0.028	0.05	-10000	0	-0.61	3	3
RAC1	0.026	0.009	-10000	0	-10000	0	0
Rac1/GTP	0.033	0.069	-10000	0	-0.58	1	1
MMP2	0.047	0.09	0.42	2	-0.6	2	4

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.014	0.064	0.85	1	-10000	0	1
VDR	0.024	0.049	-10000	0	-0.61	3	3
FAM120B	0.026	0.008	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.051	0.044	-10000	0	-0.31	1	1
RXRs/LXRs/DNA/Oxysterols	0.055	0.053	-10000	0	-0.36	4	4
MED1	0.028	0.004	-10000	0	-10000	0	0
mol:9cRA	0.006	0.006	-10000	0	-10000	0	0
RARs/THRs/DNA/Src-1	0.01	0.072	-10000	0	-10000	0	0
RXRs/NUR77	0.061	0.081	-10000	0	-0.35	13	13
RXRs/PPAR	0.03	0.036	-10000	0	-0.5	1	1
NCOR2	0.028	0.005	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.018	0.036	-10000	0	-0.45	3	3
RARs/VDR/DNA/Vit D3	0.043	0.049	-10000	0	-0.32	5	5
RARA	0.028	0.004	-10000	0	-10000	0	0
NCOA1	0.028	0.005	-10000	0	-10000	0	0
VDR/VDR/DNA	0.024	0.049	-10000	0	-0.61	3	3
RARs/RARs/DNA/9cRA	0.035	0.035	-10000	0	-0.33	2	2
RARG	0.028	0.005	-10000	0	-10000	0	0
RPS6KB1	0.019	0.071	0.51	9	-0.36	1	10
RARs/THRs/DNA/SMRT	0.01	0.071	-10000	0	-10000	0	0
THRA	0.027	0.029	-10000	0	-0.61	1	1
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.018	0.036	-10000	0	-0.45	3	3
RXRs/PPAR/9cRA/PGJ2/DNA	0.063	0.045	-10000	0	-0.33	1	1
NR1H4	0.01	0.1	-10000	0	-0.61	14	14
RXRs/LXRs/DNA	0.094	0.058	-10000	0	-10000	0	0
NR1H2	0.032	0.03	-10000	0	-0.61	1	1
NR1H3	0.034	0.01	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.065	0.05	-10000	0	-0.32	3	3
NR4A1	0.011	0.1	-10000	0	-0.6	14	14
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	0.022	0.073	-10000	0	-0.42	9	9
RXRG	0.026	0.051	-10000	0	-0.52	4	4
RXR alpha/CCPG	0.041	0.016	-10000	0	-10000	0	0
RXRA	0.032	0.011	-10000	0	-10000	0	0
RXRB	0.033	0.012	-10000	0	-10000	0	0
THRB	-0.013	0.14	-10000	0	-0.53	31	31
PPARG	0.02	0.013	-10000	0	-10000	0	0
PPARD	0.028	0.006	-10000	0	-10000	0	0
TNF	0.048	0.11	-10000	0	-1	4	4
mol:Oxysterols	0.006	0.005	-10000	0	-10000	0	0
cholesterol transport	0.055	0.053	-10000	0	-0.36	4	4
PPARA	0.028	0.004	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.018	0.042	-10000	0	-0.61	2	2
RXRs/NUR77/BCL2	0.024	0.057	-10000	0	-0.43	2	2
SREBF1	0.055	0.049	-10000	0	-10000	0	0
RXRs/RXRs/DNA/9cRA	0.063	0.045	-10000	0	-0.33	1	1
ABCA1	0.054	0.054	-10000	0	-10000	0	0
RARs/THRs	0.035	0.095	-10000	0	-10000	0	0
RXRs/FXR	0.062	0.08	-10000	0	-0.35	9	9
BCL2	0.028	0.005	-10000	0	-10000	0	0

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.028	0.006	-10000	0	-10000	0	0
NFATC1	0.039	0.072	0.37	3	-0.45	1	4
NFATC2	0.034	0.067	0.22	8	-0.26	12	20
NFATC3	0.023	0.03	-10000	0	-0.34	3	3
YWHAE	0.028	0.005	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.003	0.083	0.31	2	-0.35	10	12
Exportin 1/Ran/NUP214	0.054	0.017	-10000	0	-10000	0	0
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	0.022	0.077	-10000	0	-0.37	5	5
BCL2/BAX	0.041	0.008	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0.02	0.01	-10000	0	-10000	0	0
CaM/Ca2+	0.02	0.01	-10000	0	-10000	0	0
BAX	0.029	0.003	-10000	0	-10000	0	0
MAPK14	0.028	0.006	-10000	0	-10000	0	0
BAD	0.026	0.037	-10000	0	-0.56	2	2
CABIN1/MEF2D	0.01	0.08	0.31	1	-0.34	9	10
Calcineurin A alpha-beta B1/BCL2	0.028	0.005	-10000	0	-10000	0	0
FKBP8	0.027	0.028	-10000	0	-0.61	1	1
activation-induced cell death of T cells	-0.01	0.079	0.33	9	-0.3	1	10
KPNB1	0.028	0.005	-10000	0	-10000	0	0
KPNA2	0.028	0.005	-10000	0	-10000	0	0
XPO1	0.028	0.005	-10000	0	-10000	0	0
SFN	-0.036	0.18	-10000	0	-0.52	59	59
MAP3K8	0.026	0.034	-10000	0	-0.5	2	2
NFAT4/CK1 alpha	0.029	0.029	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	0.068	0.087	-10000	0	-0.41	4	4
CABIN1	-0.004	0.083	0.31	2	-0.36	10	12
CALM1	0.027	0.009	-10000	0	-10000	0	0
RAN	0.028	0.005	-10000	0	-10000	0	0
MAP3K1	0.026	0.008	-10000	0	-10000	0	0
CAMK4	0.022	0.03	-10000	0	-0.61	1	1
mol:Ca2+	0.001	0.004	-10000	0	-10000	0	0
MAPK3	0.028	0.006	-10000	0	-10000	0	0
YWHAH	0.028	0.004	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.038	0.033	-10000	0	-0.45	2	2
YWHAB	0.028	0.006	-10000	0	-10000	0	0
MAPK8	0.027	0.029	-10000	0	-0.61	1	1
MAPK9	0.021	0.013	-10000	0	-10000	0	0
YWHAG	0.026	0.009	-10000	0	-10000	0	0
FKBP1A	0.028	0.005	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.062	0.079	0.24	1	-0.41	2	3
PRKCH	0.027	0.008	-10000	0	-10000	0	0
CABIN1/Cbp/p300	0.039	0.026	-10000	0	-0.45	1	1
CASP3	0.029	0.004	-10000	0	-10000	0	0
PIM1	0.028	0.006	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.019	0.005	-10000	0	-10000	0	0
apoptosis	0.023	0.015	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.019	0.058	-10000	0	-0.34	6	6
PRKCB	0.022	0.057	-10000	0	-0.55	5	5
PRKCE	0.027	0.029	-10000	0	-0.61	1	1
JNK2/NFAT4	0.023	0.043	-10000	0	-0.33	2	2
BAD/BCL-XL	0.039	0.03	-10000	0	-0.41	2	2
PRKCD	0.02	0.027	-10000	0	-0.5	1	1
NUP214	0.028	0.005	-10000	0	-10000	0	0
PRKCZ	0.024	0.05	-10000	0	-0.61	3	3
PRKCA	0.028	0.005	-10000	0	-10000	0	0
PRKCG	0.001	0.11	-10000	0	-0.51	21	21
PRKCQ	0.013	0.096	-10000	0	-0.55	14	14
FKBP38/BCL2	0.04	0.023	-10000	0	-0.45	1	1
EP300	0.027	0.029	-10000	0	-0.61	1	1
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.028	0.005	-10000	0	-10000	0	0
NFATc/JNK1	0.05	0.074	0.34	2	-0.41	1	3
CaM/Ca2+/FKBP38	0.036	0.023	-10000	0	-0.4	1	1
FKBP12/FK506	0.021	0.004	-10000	0	-10000	0	0
CSNK1A1	0.015	0.011	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0.029	0.025	-10000	0	-0.37	1	1
NFATc/ERK1	0.047	0.071	-10000	0	-0.42	1	1
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	0.021	0.078	-10000	0	-0.42	3	3
NR4A1	0.044	0.12	-10000	0	-0.56	13	13
GSK3B	0.027	0.008	-10000	0	-10000	0	0
positive T cell selection	0.023	0.03	-10000	0	-0.34	3	3
NFAT1/CK1 alpha	0.017	0.037	-10000	0	-10000	0	0
RCH1/ KPNB1	0.041	0.008	-10000	0	-10000	0	0
YWHAQ	0.028	0.005	-10000	0	-10000	0	0
PRKACA	0.029	0.003	-10000	0	-10000	0	0
AKAP5	0.024	0.041	-10000	0	-0.61	2	2
MEF2D	0.027	0.01	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.027	0.007	-10000	0	-10000	0	0
NFATc/p38 alpha	0.053	0.073	0.36	3	-0.41	1	4
CREBBP	0.027	0.009	-10000	0	-10000	0	0
BCL2	0.028	0.005	-10000	0	-10000	0	0

Retinoic acid receptors-mediated signaling

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
HDAC1	0.028	0.006	-10000	0	-10000	0	0
HDAC3	0.022	0.012	-10000	0	-10000	0	0
VDR	0.024	0.049	-10000	0	-0.61	3	3
Cbp/p300/PCAF	0.039	0.044	-10000	0	-0.73	1	1
EP300	0.027	0.029	-10000	0	-0.61	1	1
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.024	0.05	-10000	0	-0.3	6	6
KAT2B	0.019	0.031	-10000	0	-0.61	1	1
MAPK14	0.028	0.006	-10000	0	-10000	0	0
AKT1	-0.003	0.054	0.22	1	-10000	0	1
RAR alpha/9cRA/Cyclin H	0.046	0.054	-10000	0	-10000	0	0
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.024	0.052	-10000	0	-0.35	2	2
CDC2	0.001	0	-10000	0	-10000	0	0
response to UV	0.001	0	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.025	0.049	-10000	0	-0.35	5	5
NCOR2	0.028	0.005	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.018	0.036	-10000	0	-0.45	3	3
RXRs/RARs/NRIP1/9cRA	0.017	0.081	0.31	1	-0.46	2	3
NCOA2	0.017	0.08	-10000	0	-0.61	8	8
NCOA3	0.028	0.006	-10000	0	-10000	0	0
NCOA1	0.028	0.005	-10000	0	-10000	0	0
VDR/VDR/DNA	0.024	0.049	-10000	0	-0.61	3	3
RARG	0.029	0.005	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.038	0.007	-10000	0	-10000	0	0
MAPK3	0.028	0.006	-10000	0	-10000	0	0
MAPK1	0.028	0.004	-10000	0	-10000	0	0
MAPK8	0.028	0.029	-10000	0	-0.61	1	1
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.042	0.064	-10000	0	-0.51	1	1
RARA	0.021	0.034	-10000	0	-0.25	2	2
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.018	0.075	-10000	0	-0.49	7	7
PRKCA	0.031	0.006	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.001	0.1	0.36	1	-0.5	3	4
RXRG	0.016	0.054	-10000	0	-0.56	1	1
RXRA	0.026	0.038	-10000	0	-10000	0	0
RXRB	0.018	0.054	-10000	0	-0.44	3	3
VDR/Vit D3/DNA	0.018	0.036	-10000	0	-0.45	3	3
RBP1	0.023	0.05	-10000	0	-0.53	4	4
CRBP1/9-cic-RA	0.017	0.036	-10000	0	-0.39	4	4
RARB	0.02	0.042	-10000	0	-0.61	2	2
PRKCG	0.004	0.11	-10000	0	-0.51	21	21
MNAT1	0.027	0.008	-10000	0	-10000	0	0
RAR alpha/RXRs	0.019	0.071	0.3	1	-0.49	2	3
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.029	0.069	0.28	2	-0.4	3	5
proteasomal ubiquitin-dependent protein catabolic process	-0.011	0.11	0.26	10	-0.34	8	18
RXRs/RARs/NRIP1/9cRA/HDAC3	0.009	0.1	0.36	2	-0.51	2	4
positive regulation of DNA binding	0.036	0.047	-10000	0	-10000	0	0
NRIP1	-0.013	0.11	-10000	0	-0.5	1	1
RXRs/RARs	-0.021	0.12	0.3	1	-0.45	5	6
RXRs/RXRs/DNA/9cRA	0.025	0.055	-10000	0	-0.44	2	2
PRKACA	0.029	0.002	-10000	0	-10000	0	0
CDK7	0.026	0.008	-10000	0	-10000	0	0
TFIIH	0.048	0.022	-10000	0	-10000	0	0
RAR alpha/9cRA	0.051	0.051	-10000	0	-10000	0	0
CCNH	0.025	0.009	-10000	0	-10000	0	0
CREBBP	0.028	0.006	-10000	0	-10000	0	0
RAR gamma2/9cRA	0.046	0.024	-10000	0	-10000	0	0

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.028	0.004	-9999	-10000	0	0
Rac1/GDP	0.023	0.012	-9999	-10000	0	0
DOCK1	0.026	0.029	-9999	-0.61	1	1
ITGA4	0.012	0.09	-9999	-0.5	15	15
RAC1	0.026	0.009	-9999	-10000	0	0
alpha4/beta7 Integrin	0.028	0.069	-9999	-0.36	15	15
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.028	0.005	-9999	-10000	0	0
alpha4/beta1 Integrin	0.044	0.063	-9999	-0.3	15	15
alpha4/beta7 Integrin/Paxillin	0.039	0.057	-9999	-10000	0	0
lamellipodium assembly	0.033	0.061	-9999	-0.5	4	4
PIK3CA	0.026	0.029	-9999	-0.61	1	1
PI3K	0.036	0.034	-9999	-0.45	2	2
ARF6	0.027	0.008	-9999	-10000	0	0
TLN1	0.028	0.006	-9999	-10000	0	0
PXN	0.02	0.004	-9999	-10000	0	0
PIK3R1	0.025	0.029	-9999	-0.61	1	1
ARF6/GTP	0.048	0.055	-9999	-10000	0	0
cell adhesion	0.049	0.058	-9999	-10000	0	0
CRKL/CBL	0.041	0.023	-9999	-0.45	1	1
alpha4/beta1 Integrin/Paxillin	0.039	0.057	-9999	-10000	0	0
ITGB1	0.028	0.004	-9999	-10000	0	0
ITGB7	0.028	0.005	-9999	-10000	0	0
ARF6/GDP	0.023	0.011	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.045	0.074	-9999	-10000	0	0
p130Cas/Crk/Dock1	0.052	0.032	-9999	-0.39	2	2
VCAM1	0.016	0.079	-9999	-0.47	13	13
alpha4/beta1 Integrin/Paxillin/Talin	0.051	0.059	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.053	0.058	-9999	-10000	0	0
BCAR1	0.027	0.029	-9999	-0.61	1	1
mol:GDP	-0.051	0.057	-9999	-10000	0	0
CBL	0.027	0.028	-9999	-0.61	1	1
PRKACA	0.029	0.002	-9999	-10000	0	0
GIT1	0.028	0.004	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.051	0.059	-9999	-10000	0	0
Rac1/GTP	0.034	0.068	-9999	-0.57	4	4

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.028	0.005	-10000	0	-10000	0	0
SMAD2	-0.029	0.067	0.23	1	-0.25	15	16
SMAD3	0.024	0.021	-10000	0	-10000	0	0
SMAD3/SMAD4	0.029	0.092	-10000	0	-0.47	12	12
SMAD4/Ubc9/PIASy	0.054	0.016	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.017	0.084	-10000	0	-10000	0	0
PPM1A	0.027	0.008	-10000	0	-10000	0	0
CALM1	0.027	0.008	-10000	0	-10000	0	0
SMAD2/SMAD4	-0.02	0.077	-10000	0	-0.3	9	9
MAP3K1	0.026	0.008	-10000	0	-10000	0	0
TRAP-1/SMAD4	0.04	0.014	-10000	0	-10000	0	0
MAPK3	0.028	0.006	-10000	0	-10000	0	0
MAPK1	0.028	0.004	-10000	0	-10000	0	0
NUP214	0.028	0.005	-10000	0	-10000	0	0
CTDSP1	0.027	0.007	-10000	0	-10000	0	0
CTDSP2	0.028	0.005	-10000	0	-10000	0	0
CTDSPL	0.02	0.013	-10000	0	-10000	0	0
KPNB1	0.028	0.005	-10000	0	-10000	0	0
TGFBRAP1	0.027	0.016	-10000	0	-0.3	1	1
UBE2I	0.028	0.006	-10000	0	-10000	0	0
NUP153	0.028	0.005	-10000	0	-10000	0	0
KPNA2	0.028	0.005	-10000	0	-10000	0	0
PIAS4	0.029	0.003	-10000	0	-10000	0	0

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.065	0.03	-10000	0	-0.35	1	1
HDAC3	0.022	0.012	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0.007	0.002	-10000	0	-10000	0	0
GATA1/HDAC4	0.025	0.075	-10000	0	-0.36	18	18
GATA1/HDAC5	0.024	0.08	-10000	0	-0.37	20	20
GATA2/HDAC5	0.029	0.071	-10000	0	-0.45	10	10
HDAC5/BCL6/BCoR	0.053	0.025	-10000	0	-0.39	1	1
HDAC9	0.026	0.009	-10000	0	-10000	0	0
Glucocorticoid receptor/Hsp90/HDAC6	0.041	0.031	-10000	0	-0.3	1	1
HDAC4/ANKRA2	0.036	0.016	-10000	0	-10000	0	0
HDAC5/YWHAB	0.039	0.024	-10000	0	-0.45	1	1
NPC/RanGAP1/SUMO1/Ubc9	0.02	0.007	-10000	0	-10000	0	0
GATA2	0.014	0.09	-10000	0	-0.58	11	11
HDAC4/RFXANK	0.039	0.021	-10000	0	-0.36	1	1
BCOR	0.029	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.027	0.029	-10000	0	-0.61	1	1
HDAC5	0.027	0.029	-10000	0	-0.61	1	1
GNB1/GNG2	0.038	0.013	-10000	0	-10000	0	0
Histones	0.029	0.044	-10000	0	-0.7	1	1
ADRBK1	0.029	0.003	-10000	0	-10000	0	0
HDAC4	0.027	0.007	-10000	0	-10000	0	0
XPO1	0.028	0.005	-10000	0	-10000	0	0
HDAC5/ANKRA2	0.037	0.026	-10000	0	-0.45	1	1
HDAC4/Ubc9	0.039	0.013	-10000	0	-10000	0	0
HDAC7	0.028	0.005	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.04	0.023	-10000	0	-0.45	1	1
TUBA1B	0.028	0.005	-10000	0	-10000	0	0
HDAC6	0.029	0.003	-10000	0	-10000	0	0
HDAC5/RFXANK	0.04	0.029	-10000	0	-0.41	2	2
CAMK4	0.022	0.03	-10000	0	-0.61	1	1
Tubulin/HDAC6	0.053	0.025	-10000	0	-0.39	1	1
SUMO1	0.027	0.006	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.028	0.006	-10000	0	-10000	0	0
GATA1	0.007	0.1	-10000	0	-0.5	19	19
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.028	0.005	-10000	0	-10000	0	0
NR3C1	0.021	0.026	-10000	0	-0.5	1	1
SUMO1/HDAC4	0.049	0.028	-10000	0	-10000	0	0
SRF	0.028	0.006	-10000	0	-10000	0	0
HDAC4/YWHAB	0.039	0.012	-10000	0	-10000	0	0
Tubulin	0.039	0.024	-10000	0	-0.45	1	1
HDAC4/14-3-3 E	0.04	0.011	-10000	0	-10000	0	0
GNB1	0.028	0.006	-10000	0	-10000	0	0
RANGAP1	0.028	0.004	-10000	0	-10000	0	0
BCL6/BCoR	0.04	0.01	-10000	0	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0.041	0.027	-10000	0	-10000	0	0
HDAC4/SRF	0.043	0.032	-10000	0	-0.39	1	1
HDAC4/ER alpha	0.034	0.039	-10000	0	-0.42	3	3
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.029	0.043	-10000	0	-0.69	1	1
cell motility	0.053	0.025	-10000	0	-0.38	1	1
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.028	0.006	-10000	0	-10000	0	0
HDAC7/HDAC3	0.032	0.019	-10000	0	-10000	0	0
BCL6	0.027	0.006	-10000	0	-10000	0	0
HDAC4/CaMK II delta B	0.027	0.007	-10000	0	-10000	0	0
Hsp90/HDAC6	0.039	0.012	-10000	0	-10000	0	0
ESR1	0.022	0.049	-10000	0	-0.51	4	4
HDAC6/HDAC11	0.029	0.029	-10000	0	-0.45	1	1
Ran/GTP/Exportin 1	0.049	0.03	-10000	0	-10000	0	0
NPC	0.017	0.003	-10000	0	-10000	0	0
MEF2C	0.025	0.01	-10000	0	-10000	0	0
RAN	0.028	0.005	-10000	0	-10000	0	0
HDAC4/MEF2C	0.059	0.04	-10000	0	-10000	0	0
GNG2	0.027	0.008	-10000	0	-10000	0	0
NCOR2	0.028	0.005	-10000	0	-10000	0	0
TUBB2A	0.027	0.029	-10000	0	-0.61	1	1
HDAC11	0.019	0.031	-10000	0	-0.61	1	1
HSP90AA1	0.027	0.008	-10000	0	-10000	0	0
RANBP2	0.028	0.005	-10000	0	-10000	0	0
ANKRA2	0.026	0.009	-10000	0	-10000	0	0
RFXANK	0.028	0.024	-10000	0	-0.5	1	1
nuclear import	-0.038	0.021	0.34	1	-10000	0	1

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.061	0.03	-10000	0	-10000	0	0
CLOCK	0.03	0.029	-10000	0	-0.61	1	1
TIMELESS/CRY2	0.051	0.026	-10000	0	-10000	0	0
DEC1/BMAL1	0.036	0.02	-10000	0	-0.36	1	1
ATR	0.027	0.007	-10000	0	-10000	0	0
NR1D1	0.03	0.063	-10000	0	-1.2	1	1
ARNTL	0.031	0.006	-10000	0	-10000	0	0
TIMELESS	0.033	0.023	-10000	0	-10000	0	0
NPAS2	0.022	0.069	-10000	0	-0.47	9	9
CRY2	0.029	0.003	-10000	0	-10000	0	0
mol:CO	-0.012	0.008	0.1	2	-10000	0	2
CHEK1	0.029	0.003	-10000	0	-10000	0	0
mol:HEME	0.012	0.008	-10000	0	-0.1	2	2
PER1	0.028	0.005	-10000	0	-10000	0	0
BMAL/CLOCK/NPAS2	0.065	0.049	-10000	0	-0.38	4	4
BMAL1/CLOCK	0.044	0.06	-10000	0	-0.8	1	1
S phase of mitotic cell cycle	0.061	0.03	-10000	0	-10000	0	0
TIMELESS/CHEK1/ATR	0.062	0.03	-10000	0	-10000	0	0
mol:NADPH	0.012	0.008	-10000	0	-0.1	2	2
PER1/TIMELESS	0.05	0.026	-10000	0	-10000	0	0
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.018	0.024	-10000	0	-0.5	1	1

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.014	0.087	-10000	0	-10000	0	0
regulation of axonogenesis	-0.008	0.053	-10000	0	-10000	0	0
myoblast fusion	-0.018	0.051	0.3	2	-10000	0	2
mol:GTP	0.012	0.042	-10000	0	-0.36	1	1
regulation of calcium-dependent cell-cell adhesion	-0.045	0.048	-10000	0	-10000	0	0
ARF1/GTP	0.023	0.045	-10000	0	-0.28	1	1
mol:GM1	0.001	0.037	-10000	0	-0.28	1	1
mol:Choline	0.011	0.03	-10000	0	-10000	0	0
lamellipodium assembly	0.005	0.073	-10000	0	-0.33	15	15
MAPK3	0.017	0.052	-10000	0	-0.41	1	1
ARF6/GTP/NME1/Tiam1	0.046	0.049	-10000	0	-10000	0	0
ARF1	0.028	0.006	-10000	0	-10000	0	0
ARF6/GDP	0.018	0.051	-10000	0	-0.31	2	2
ARF1/GDP	0.015	0.071	-10000	0	-0.31	2	2
ARF6	0.027	0.025	-10000	0	-10000	0	0
RAB11A	0.029	0.003	-10000	0	-10000	0	0
TIAM1	0.029	0.008	-10000	0	-10000	0	0
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.018	0.051	-10000	0	-10000	0	0
actin filament bundle formation	-0.009	0.069	0.31	2	-10000	0	2
KALRN	0.012	0.04	-10000	0	-0.31	1	1
RAB11FIP3/RAB11A	0.041	0.01	-10000	0	-10000	0	0
RhoA/GDP	0.009	0.07	-10000	0	-0.31	2	2
NME1	0.029	0.007	-10000	0	-10000	0	0
Rac1/GDP	0.021	0.065	-10000	0	-0.34	1	1
substrate adhesion-dependent cell spreading	0.012	0.042	-10000	0	-0.36	1	1
cortical actin cytoskeleton organization	0.005	0.074	-10000	0	-0.33	15	15
RAC1	0.026	0.009	-10000	0	-10000	0	0
liver development	0.012	0.042	-10000	0	-0.36	1	1
ARF6/GTP	0.012	0.042	-10000	0	-0.36	1	1
RhoA/GTP	0.016	0.043	-10000	0	-0.28	1	1
mol:GDP	0.003	0.061	-10000	0	-0.37	1	1
ARF6/GTP/RAB11FIP3/RAB11A	0.04	0.045	-10000	0	-0.24	1	1
RHOA	0.021	0.013	-10000	0	-10000	0	0
PLD1	0.014	0.036	-10000	0	-10000	0	0
RAB11FIP3	0.028	0.006	-10000	0	-10000	0	0
tube morphogenesis	0.005	0.073	-10000	0	-0.33	15	15
ruffle organization	0.008	0.053	-10000	0	-10000	0	0
regulation of epithelial cell migration	0.012	0.042	-10000	0	-0.36	1	1
PLD2	0.013	0.039	-10000	0	-10000	0	0
PIP5K1A	0.008	0.053	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.011	0.03	-10000	0	-10000	0	0
Rac1/GTP	0.005	0.074	-10000	0	-0.33	15	15

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	0.047	0.057	-10000	0	-0.4	3	3
Ran/GTP/Exportin 1/HDAC1	0.007	0.002	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.035	0.052	-10000	0	-0.36	3	3
SUMO1	0.027	0.006	-10000	0	-10000	0	0
ZFPM1	0.024	0.049	-10000	0	-0.61	3	3
NPC/RanGAP1/SUMO1/Ubc9	0.02	0.007	-10000	0	-10000	0	0
FKBP3	0.027	0.008	-10000	0	-10000	0	0
Histones	0.053	0.043	-10000	0	-10000	0	0
YY1/LSF	0.004	0.069	-10000	0	-0.62	1	1
SMG5	0.027	0.006	-10000	0	-10000	0	0
RAN	0.028	0.005	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	0.023	0.031	-10000	0	-0.28	2	2
I kappa B alpha/HDAC1	0.027	0.038	-10000	0	-10000	0	0
SAP18	0.028	0.005	-10000	0	-10000	0	0
RELA	0.024	0.034	-10000	0	-0.24	2	2
HDAC1/Smad7	0.05	0.021	-10000	0	-10000	0	0
RANGAP1	0.028	0.004	-10000	0	-10000	0	0
HDAC3/TR2	0.031	0.03	-10000	0	-10000	0	0
NuRD/MBD3 Complex	0.039	0.025	-10000	0	-0.29	1	1
NF kappa B1 p50/RelA	0.073	0.069	0.28	8	-0.53	1	9
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	0.014	0.09	-10000	0	-0.58	11	11
GATA1	0.007	0.1	-10000	0	-0.5	19	19
Mad/Max	0.039	0.013	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.04	0.067	-10000	0	-0.36	7	7
RBBP7	0.029	0.003	-10000	0	-10000	0	0
NPC	0.017	0.003	-10000	0	-10000	0	0
RBBP4	0.027	0.029	-10000	0	-0.61	1	1
MAX	0.027	0.008	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.022	0.013	-10000	0	-10000	0	0
NFKBIA	0.019	0.027	-10000	0	-10000	0	0
KAT2B	0.019	0.031	-10000	0	-0.61	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.031	0.04	-10000	0	-0.38	2	2
SIN3 complex	0.059	0.064	-10000	0	-10000	0	0
SMURF1	0.026	0.009	-10000	0	-10000	0	0
CHD3	0.028	0.005	-10000	0	-10000	0	0
SAP30	0.011	0.096	-10000	0	-0.5	17	17
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.028	0.005	-10000	0	-10000	0	0
YY1/HDAC3	0.014	0.051	-10000	0	-0.55	1	1
YY1/HDAC2	0.006	0.068	-10000	0	-0.62	1	1
YY1/HDAC1	0.004	0.069	-10000	0	-0.62	1	1
NuRD/MBD2 Complex (MeCP1)	0.04	0.021	-10000	0	-10000	0	0
PPARG	0.019	0.037	-10000	0	-0.34	2	2
HDAC8/hEST1B	0.056	0.013	-10000	0	-10000	0	0
UBE2I	0.028	0.006	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.022	0.013	-10000	0	-10000	0	0
TNFRSF1A	0.028	0.006	-10000	0	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.031	0.03	-10000	0	-10000	0	0
MBD3L2	0.018	0.002	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.049	0.021	-10000	0	-10000	0	0
CREBBP	0.028	0.006	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.041	0.062	-10000	0	-0.35	6	6
HDAC1	0.028	0.006	-10000	0	-10000	0	0
HDAC3	0.021	0.025	-10000	0	-10000	0	0
HDAC2	0.027	0.008	-10000	0	-10000	0	0
YY1	0.019	0.035	-10000	0	-0.7	1	1
HDAC8	0.029	0.001	-10000	0	-10000	0	0
SMAD7	0.028	0.005	-10000	0	-10000	0	0
NCOR2	0.028	0.005	-10000	0	-10000	0	0
MXD1	0.028	0.005	-10000	0	-10000	0	0
STAT3	0.026	0.018	-10000	0	-0.35	1	1
NFKB1	0.027	0.029	-10000	0	-0.61	1	1
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.028	0.005	-10000	0	-10000	0	0
YY1/LSF/HDAC1	0.017	0.069	-10000	0	-0.58	1	1
YY1/SAP30/HDAC1	0.008	0.088	-10000	0	-0.41	6	6
EP300	0.027	0.029	-10000	0	-0.61	1	1
STAT3 (dimer non-phopshorylated)	0.026	0.018	-10000	0	-0.35	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.019	0.027	-10000	0	-10000	0	0
histone deacetylation	0.042	0.049	-10000	0	-0.43	4	4
STAT3 (dimer non-phopshorylated)/HDAC3	0.03	0.03	-10000	0	-10000	0	0
nuclear export	-0.055	0.013	-10000	0	-10000	0	0
PRKACA	0.029	0.002	-10000	0	-10000	0	0
GATAD2B	0.027	0.006	-10000	0	-10000	0	0
GATAD2A	0.029	0.003	-10000	0	-10000	0	0
GATA2/HDAC3	0.025	0.055	-10000	0	-0.34	7	7
GATA1/HDAC1	0.025	0.077	-10000	0	-0.36	19	19
GATA1/HDAC3	0.023	0.055	-10000	0	-10000	0	0
CHD4	0.028	0.006	-10000	0	-10000	0	0
TNF-alpha/TNFR1A	0.033	0.057	-10000	0	-0.41	8	8
SIN3/HDAC complex/Mad/Max	0.035	0.038	-10000	0	-0.37	2	2
NuRD Complex	0.046	0.06	-10000	0	-0.35	4	4
positive regulation of chromatin silencing	0.05	0.041	-10000	0	-10000	0	0
SIN3B	0.029	0.003	-10000	0	-10000	0	0
MTA2	0.029	0.003	-10000	0	-10000	0	0
SIN3A	0.029	0.003	-10000	0	-10000	0	0
XPO1	0.028	0.005	-10000	0	-10000	0	0
SUMO1/HDAC1	0.048	0.028	-10000	0	-10000	0	0
HDAC complex	0.066	0.029	-10000	0	-0.35	1	1
GATA1/Fog1	0.023	0.082	-10000	0	-0.38	20	20
FKBP25/HDAC1/HDAC2	0.05	0.021	-10000	0	-10000	0	0
TNF	0.018	0.073	-10000	0	-0.56	8	8
negative regulation of cell growth	0.03	0.064	-10000	0	-0.37	9	9
NuRD/MBD2/PRMT5 Complex	0.04	0.021	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.049	0.03	-10000	0	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.026	0.038	-10000	0	-0.34	2	2
SIN3/HDAC complex/NCoR1	0.035	0.037	-10000	0	-0.32	1	1
TFCP2	0.028	0.005	-10000	0	-10000	0	0
NR2C1	0.028	0.005	-10000	0	-10000	0	0
MBD3	0.026	0.037	-10000	0	-0.56	2	2
MBD2	0.028	0.005	-10000	0	-10000	0	0

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.041	0.026	-10000	0	-0.36	2	2
FBXW11	0.022	0.013	-10000	0	-10000	0	0
NF kappa B1 p50/c-Rel	0.03	0.035	-10000	0	-0.39	3	3
NF kappa B1 p50/RelA/I kappa B alpha	0.029	0.06	-10000	0	-0.32	1	1
NFKBIA	0.017	0.04	-10000	0	-0.32	2	2
MAPK14	0.028	0.006	-10000	0	-10000	0	0
NF kappa B1 p105/p50	0.025	0.025	-10000	0	-0.39	1	1
ARRB2	0.018	0.026	-10000	0	-0.56	1	1
REL	0.025	0.043	-10000	0	-0.51	3	3
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	0.031	0.029	-10000	0	-0.35	2	2
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	0.033	0.022	-10000	0	-0.39	1	1
PIK3CA	0.026	0.029	-10000	0	-0.61	1	1
NF kappa B1 p50 dimer	0.023	0.022	-10000	0	-0.45	1	1
PIK3R1	0.025	0.029	-10000	0	-0.61	1	1
NFKB1	0.018	0.022	-10000	0	-0.45	1	1
RELA	0.029	0.003	-10000	0	-10000	0	0
positive regulation of anti-apoptosis	0.02	0.041	-10000	0	-0.28	2	2
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.032	0.066	-10000	0	-0.46	1	1
SRC	0.028	0.006	-10000	0	-10000	0	0
PI3K	0.036	0.034	-10000	0	-0.45	2	2
NF kappa B1 p50/RelA	0.021	0.038	-10000	0	-0.29	2	2
IKBKB	0.027	0.008	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.022	0.013	-10000	0	-10000	0	0
SYK	0.026	0.032	-10000	0	-0.46	2	2
I kappa B alpha/PIK3R1	0.019	0.062	0.28	1	-0.36	3	4
cell death	0.03	0.064	-10000	0	-0.44	1	1
NF kappa B1 p105/c-Rel	0.03	0.035	-10000	0	-0.39	3	3
LCK	0.004	0.11	-10000	0	-0.51	22	22
BCL3	0.026	0.033	-10000	0	-0.5	2	2

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.05	0.074	0.31	8	-0.44	1	9
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.015	0.051	0.15	1	-0.29	9	10
AP2	0.04	0.01	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.036	0.014	-10000	0	-10000	0	0
CLTB	0.021	0.013	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.019	0.013	-10000	0	-10000	0	0
CD4	0.018	0.07	-10000	0	-0.5	9	9
CLTA	0.028	0.006	-10000	0	-10000	0	0
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
ARFGAP1	0.009	0.021	-10000	0	-0.45	1	1
mol:PI-4-5-P2	0.01	0.016	-10000	0	-0.34	1	1
ARF1/GTP	0.034	0.013	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.014	0.02	-10000	0	-0.38	1	1
mol:Choline	0.009	0.016	-10000	0	-0.33	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.028	0.007	-10000	0	-10000	0	0
DDEF1	0.009	0.016	-10000	0	-0.34	1	1
ARF1/GDP	0.006	0.02	-10000	0	-0.37	1	1
AP2M1	0.027	0.006	-10000	0	-10000	0	0
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	0.015	0.006	-10000	0	-10000	0	0
Rac/GTP	0.02	0.007	-10000	0	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.04	0.021	-10000	0	-0.34	1	1
ARFIP2	0.026	0.009	-10000	0	-10000	0	0
COPA	0.027	0.006	-10000	0	-10000	0	0
RAC1	0.026	0.009	-10000	0	-10000	0	0
ARF1/GTP/coatomer protein complex	0.01	0.043	-10000	0	-0.28	8	8
ARF1/GTP/ARHGAP10	0.019	0.005	-10000	0	-10000	0	0
GGA3	0.028	0.005	-10000	0	-10000	0	0
ARF1/GTP/Membrin	0.026	0.03	-10000	0	-0.23	6	6
AP2A1	0.029	0.003	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.017	0.017	-10000	0	-10000	0	0
ARF1/GDP/Membrin	0.026	0.038	-10000	0	-0.3	6	6
Arfaptin 2/Rac/GDP	0.035	0.013	-10000	0	-10000	0	0
CYTH2	0.03	0.005	-10000	0	-10000	0	0
ARF1/GTP/GGA3	0.038	0.01	-10000	0	-10000	0	0
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.019	0.007	-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	0.02	0.024	-10000	0	-10000	0	0
PLD2	0.009	0.016	-10000	0	-0.34	1	1
ARF-GAP1/v-SNARE	0.009	0.021	-10000	0	-0.45	1	1
PIP5K1A	0.01	0.016	-10000	0	-0.34	1	1
ARF1/GTP/Membrin/GBF1/p115	0.025	0.02	-10000	0	-10000	0	0
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.009	0.016	-10000	0	-0.33	1	1
KDEL Receptor/Ligand/ARF-GAP1	0.009	0.021	-10000	0	-0.45	1	1
GOSR2	0.016	0.009	-10000	0	-10000	0	0
USO1	0.014	0.026	-10000	0	-0.3	3	3
GBF1	0.009	0.049	-10000	0	-0.3	12	12
ARF1/GTP/Arfaptin 2	0.04	0.01	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.047	0.05	-10000	0	-0.3	9	9

TRAIL signaling 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
TNFSF10	0.026	0.029	-10000	0	-0.61	1	1
positive regulation of NF-kappaB transcription factor activity	0.036	0.026	-10000	0	-0.45	1	1
MAP2K4	0.032	0.033	-10000	0	-10000	0	0
IKBKB	0.027	0.008	-10000	0	-10000	0	0
TNFRSF10B	0.025	0.025	-10000	0	-0.5	1	1
TNFRSF10A	0.025	0.017	-10000	0	-0.3	1	1
SMPD1	0.017	0.013	-10000	0	-0.22	1	1
IKBKG	0.028	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.026	0.009	-10000	0	-10000	0	0
TRAIL/TRAILR2	0.036	0.027	-10000	0	-0.45	1	1
TRAIL/TRAILR3	0.036	0.026	-10000	0	-0.45	1	1
TRAIL/TRAILR1	0.036	0.026	-10000	0	-0.45	1	1
TRAIL/TRAILR4	0.036	0.026	-10000	0	-0.45	1	1
TRAIL/TRAILR1/DAP3/GTP	0.045	0.028	-10000	0	-0.35	1	1
IKK complex	0.033	0.035	-10000	0	-10000	0	0
RIPK1	0.028	0.005	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.02	0.005	-10000	0	-10000	0	0
MAPK3	0.018	0.022	-10000	0	-0.45	1	1
MAP3K1	0.035	0.031	-10000	0	-10000	0	0
TRAILR4 (trimer)	0.026	0.009	-10000	0	-10000	0	0
TRADD	0.028	0.006	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.025	0.017	-10000	0	-0.3	1	1
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.033	0.021	-10000	0	-10000	0	0
CFLAR	0.028	0.006	-10000	0	-10000	0	0
MAPK1	0.019	0.021	-10000	0	-0.45	1	1
TRAIL/TRAILR1/FADD/TRADD/RIP	0.07	0.038	-10000	0	-0.33	1	1
mol:ceramide	0.017	0.013	-10000	0	-0.22	1	1
FADD	0.029	0.003	-10000	0	-10000	0	0
MAPK8	0.03	0.043	0.28	1	-10000	0	1
TRAF2	0.028	0.005	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.026	0.009	-10000	0	-10000	0	0
CHUK	0.028	0.006	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	0.05	0.028	-10000	0	-0.39	1	1
DAP3	0.027	0.006	-10000	0	-10000	0	0
CASP10	0.017	0.028	-10000	0	-0.38	1	1
JNK cascade	0.036	0.026	-10000	0	-0.45	1	1
TRAIL (trimer)	0.026	0.029	-10000	0	-0.61	1	1
TNFRSF10C	0.026	0.009	-10000	0	-10000	0	0
TRAIL/TRAILR1/DAP3/GTP/FADD	0.056	0.031	-10000	0	-0.33	1	1
TRAIL/TRAILR2/FADD	0.05	0.029	-10000	0	-0.39	1	1
cell death	0.017	0.013	-10000	0	-0.22	1	1
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.033	0.022	-10000	0	-10000	0	0
TRAILR2 (trimer)	0.025	0.025	-10000	0	-0.5	1	1
CASP8	0.004	0.081	-10000	0	-0.59	9	9
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.069	0.038	-10000	0	-0.33	1	1

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	0.028	0.006	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0.001	-10000	0	-10000	0	0
MDM2/SUMO1	0.047	0.029	-10000	0	-10000	0	0
HDAC4	0.027	0.007	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	0	0.001	-10000	0	-10000	0	0
SUMO1	0.027	0.006	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1	0.014	0.023	-10000	0	-0.18	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
XPO1	0.019	0.007	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
RAN	0.028	0.005	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.028	0.005	-10000	0	-10000	0	0
SUMO1/HDAC4	0.049	0.028	-10000	0	-10000	0	0
SUMO1/HDAC1	0.048	0.028	-10000	0	-10000	0	0
RANGAP1	0.028	0.004	-10000	0	-10000	0	0
MDM2/SUMO1/SUMO1	0.067	0.022	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.02	0.007	-10000	0	-10000	0	0
Ran/GTP	0.035	0.028	-10000	0	-10000	0	0
EntrezGene:23225	0	0	-10000	0	-10000	0	0
MDM2	0.028	0.005	-10000	0	-10000	0	0
UBE2I	0.028	0.006	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.035	0.028	0.25	1	-10000	0	1
NPC	0.017	0.003	-10000	0	-10000	0	0
PIAS2	0.028	0.005	-10000	0	-10000	0	0
PIAS1	0.029	0.003	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0.045	0.017	-10000	0	-10000	0	0
MAPK9	0.007	0.004	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.007	0.03	0.19	1	-0.36	3	4
GNB1/GNG2	0.035	0.012	-10000	0	-10000	0	0
GNB1	0.028	0.006	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.01	0.002	-10000	0	-10000	0	0
Gs family/GTP	0.018	0.003	-10000	0	-10000	0	0
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	0	-10000	0	-10000	0	0
GNAL	0.028	0.005	-10000	0	-10000	0	0
GNG2	0.027	0.008	-10000	0	-10000	0	0
CRH	0.016	0.041	-10000	0	-0.5	3	3
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.009	0.017	-10000	0	-0.37	1	1
MAPK11	0.009	0.01	-10000	0	-0.21	1	1

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.038	0.037	-9999	-0.36	4	4
FBXW11	0.022	0.013	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.022	0.013	-9999	-10000	0	0
CHUK	0.028	0.006	-9999	-10000	0	0
NF kappa B2 p100/RelB	0.059	0.045	-9999	-10000	0	0
NFKB1	0.027	0.029	-9999	-0.61	1	1
MAP3K14	0.024	0.047	-9999	-0.5	4	4
NF kappa B1 p50/RelB	0.041	0.023	-9999	-0.45	1	1
RELB	0.029	0.003	-9999	-10000	0	0
NFKB2	0.028	0.006	-9999	-10000	0	0
NF kappa B2 p52/RelB	0.037	0.009	-9999	-10000	0	0
regulation of B cell activation	0.037	0.009	-9999	-10000	0	0

pid_entity	TCGA.MW.A4EC	TCGA.MM.A564	TCGA.GK.A6C7	TCGA.G6.A5PC
109_MAP3K5	0	0.048	0.048	-0.044
47_PPARGC1A	0.029	0.029	0.029	0.029
105_BMP4	0.029	0.029	0.029	0
105_BMP6	0.029	0.029	0.029	0.029
105_BMP7	0.018	-0.61	-0.61	0.018
105_BMP2	0.029	0.029	0.029	0.029
131_RELN/VLDLR	-0.35	-0.35	-0.35	-0.35
30_TGFB1/TGF beta receptor Type II	0.028	0.033	0.029	0.028
84_STAT5B	-0.054	-0.14	-0.03	-0.28
84_STAT5A	-0.054	-0.14	-0.03	-0.28