PARADIGM pathway analysis of mRNASeq expression data - Brain Lower Grade Glioma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
Ephrin A reverse signaling	132
IL23-mediated signaling events	116
FOXM1 transcription factor network	100
TCGA08_retinoblastoma	96
IL12-mediated signaling events	91
Aurora B signaling	87
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	82
Syndecan-1-mediated signaling events	79
E-cadherin signaling events	78
Effects of Botulinum toxin	76

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
Ephrin A reverse signaling	0.2558	132	924	7	-0.15	0	1000	-1000	-0.031	-1000
IL23-mediated signaling events	0.2248	116	7017	60	-0.68	0.014	1000	-1000	-0.15	-1000
FOXM1 transcription factor network	0.1938	100	5127	51	-0.41	0.025	1000	-1000	-0.15	-1000
TCGA08_retinoblastoma	0.1860	96	773	8	-0.097	0.075	1000	-1000	-0.016	-1000
IL12-mediated signaling events	0.1764	91	7945	87	-0.56	0.12	1000	-1000	-0.11	-1000
Aurora B signaling	0.1686	87	5845	67	-0.34	0.014	1000	-1000	-0.059	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.1589	82	5576	68	-0.48	0.23	1000	-1000	-0.1	-1000
Syndecan-1-mediated signaling events	0.1531	79	2699	34	-0.23	0.014	1000	-1000	-0.054	-1000
E-cadherin signaling events	0.1512	78	392	5	-0.12	0.014	1000	-1000	-0.043	-1000
Effects of Botulinum toxin	0.1473	76	1998	26	-0.2	0.014	1000	-1000	-0.056	-1000
TCR signaling in naïve CD8+ T cells	0.1395	72	6698	93	-0.21	0.067	1000	-1000	-0.067	-1000
Signaling events mediated by the Hedgehog family	0.1376	71	3718	52	-0.19	0.15	1000	-1000	-0.065	-1000
Signaling mediated by p38-alpha and p38-beta	0.1240	64	2859	44	-0.15	0.014	1000	-1000	-0.046	-1000
IL4-mediated signaling events	0.1182	61	5592	91	-0.61	0.44	1000	-1000	-0.15	-1000
Thromboxane A2 receptor signaling	0.1124	58	6194	105	-0.21	0.057	1000	-1000	-0.053	-1000
Syndecan-4-mediated signaling events	0.1105	57	3847	67	-0.18	0.037	1000	-1000	-0.088	-1000
Glypican 2 network	0.1085	56	224	4	-0.059	-0.015	1000	-1000	-0.038	-1000
Signaling events regulated by Ret tyrosine kinase	0.1047	54	4434	82	-0.18	0.014	1000	-1000	-0.076	-1000
Aurora C signaling	0.1027	53	371	7	-0.16	0	1000	-1000	-0.036	-1000
Reelin signaling pathway	0.1027	53	2999	56	-0.28	0.014	1000	-1000	-0.068	-1000
a4b1 and a4b7 Integrin signaling	0.1008	52	264	5	-0.077	-0.034	1000	-1000	-0.036	-1000
Endothelins	0.0988	51	4910	96	-0.19	0.014	1000	-1000	-0.072	-1000
amb2 Integrin signaling	0.0969	50	4143	82	-0.23	0.014	1000	-1000	-0.081	-1000
Visual signal transduction: Cones	0.0950	49	1892	38	-0.15	0.017	1000	-1000	-0.053	-1000
Caspase cascade in apoptosis	0.0930	48	3588	74	-0.19	0.043	1000	-1000	-0.049	-1000
Glypican 1 network	0.0930	48	2308	48	-0.17	0.03	1000	-1000	-0.044	-1000
FOXA2 and FOXA3 transcription factor networks	0.0891	46	2143	46	-0.27	0.02	1000	-1000	-0.057	-1000
Visual signal transduction: Rods	0.0891	46	2416	52	-0.2	0.014	1000	-1000	-0.075	-1000
Ras signaling in the CD4+ TCR pathway	0.0833	43	736	17	-0.12	0.023	1000	-1000	-0.04	-1000
HIF-1-alpha transcription factor network	0.0814	42	3211	76	-0.19	0.087	1000	-1000	-0.1	-1000
PDGFR-alpha signaling pathway	0.0814	42	1860	44	-0.17	0.028	1000	-1000	-0.058	-1000
Arf6 signaling events	0.0795	41	2578	62	-0.2	0.014	1000	-1000	-0.056	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0795	41	3510	85	-0.15	0.014	1000	-1000	-0.07	-1000
p75(NTR)-mediated signaling	0.0795	41	5180	125	-0.16	0.014	1000	-1000	-0.091	-1000
IL1-mediated signaling events	0.0795	41	2545	62	-0.19	0.064	1000	-1000	-0.082	-1000
Calcium signaling in the CD4+ TCR pathway	0.0795	41	1293	31	-0.18	0.014	1000	-1000	-0.075	-1000
PLK1 signaling events	0.0775	40	3417	85	-0.17	0.041	1000	-1000	-0.039	-1000
PLK2 and PLK4 events	0.0736	38	115	3	-0.018	-0.012	1000	-1000	-0.015	-1000
Glucocorticoid receptor regulatory network	0.0736	38	4405	114	-0.43	0.23	1000	-1000	-0.065	-1000
TCGA08_p53	0.0736	38	268	7	-0.074	0.048	1000	-1000	-0.008	-1000
LPA receptor mediated events	0.0736	38	3877	102	-0.18	0.019	1000	-1000	-0.079	-1000
Osteopontin-mediated events	0.0717	37	1443	38	-0.13	0.016	1000	-1000	-0.097	-1000
Nongenotropic Androgen signaling	0.0717	37	1941	52	-0.1	0.038	1000	-1000	-0.057	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0678	35	1199	34	-0.063	0.014	1000	-1000	-0.051	-1000
EGFR-dependent Endothelin signaling events	0.0678	35	740	21	-0.11	0.014	1000	-1000	-0.066	-1000
BMP receptor signaling	0.0659	34	2812	81	-0.18	0.05	1000	-1000	-0.079	-1000
BCR signaling pathway	0.0659	34	3425	99	-0.17	0.03	1000	-1000	-0.083	-1000
IL6-mediated signaling events	0.0640	33	2508	75	-0.15	0.064	1000	-1000	-0.076	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0640	33	2960	88	-0.18	0.019	1000	-1000	-0.091	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0620	32	1202	37	-0.14	0.014	1000	-1000	-0.051	-1000
Retinoic acid receptors-mediated signaling	0.0620	32	1876	58	-0.19	0.016	1000	-1000	-0.064	-1000
Fc-epsilon receptor I signaling in mast cells	0.0601	31	3085	97	-0.19	0.039	1000	-1000	-0.074	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0601	31	1637	52	-0.19	0.027	1000	-1000	-0.055	-1000
Rapid glucocorticoid signaling	0.0601	31	631	20	-0.18	0.014	1000	-1000	-0.03	-1000
Coregulation of Androgen receptor activity	0.0581	30	2296	76	-0.14	0.027	1000	-1000	-0.04	-1000
JNK signaling in the CD4+ TCR pathway	0.0581	30	517	17	-0.072	0.014	1000	-1000	-0.051	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0581	30	3619	120	-0.21	0.13	1000	-1000	-0.071	-1000
ErbB2/ErbB3 signaling events	0.0562	29	1948	65	-0.17	0.023	1000	-1000	-0.061	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0562	29	1606	54	-0.16	0.029	1000	-1000	-0.086	-1000
Syndecan-2-mediated signaling events	0.0562	29	2069	69	-0.16	0.034	1000	-1000	-0.05	-1000
Wnt signaling	0.0543	28	200	7	-0.033	-0.013	1000	-1000	-0.025	-1000
IL2 signaling events mediated by STAT5	0.0543	28	637	22	-0.094	0.019	1000	-1000	-0.035	-1000
LPA4-mediated signaling events	0.0523	27	327	12	-0.053	0.014	1000	-1000	-0.02	-1000
Regulation of nuclear SMAD2/3 signaling	0.0523	27	3768	136	-0.22	0.22	1000	-1000	-0.064	-1000
Presenilin action in Notch and Wnt signaling	0.0523	27	1648	61	-0.28	0.031	1000	-1000	-0.065	-1000
S1P5 pathway	0.0523	27	466	17	-0.13	0.053	1000	-1000	-0.036	-1000
Signaling events mediated by HDAC Class III	0.0484	25	1024	40	-0.12	0.1	1000	-1000	-0.043	-1000
FAS signaling pathway (CD95)	0.0484	25	1191	47	-0.15	0.016	1000	-1000	-0.046	-1000
IL27-mediated signaling events	0.0484	25	1275	51	-0.16	0.018	1000	-1000	-0.064	-1000
Cellular roles of Anthrax toxin	0.0465	24	936	39	-0.16	0.019	1000	-1000	-0.028	-1000
E-cadherin signaling in the nascent adherens junction	0.0465	24	1839	76	-0.12	0.014	1000	-1000	-0.076	-1000
IL2 signaling events mediated by PI3K	0.0446	23	1380	58	-0.095	0.032	1000	-1000	-0.076	-1000
Canonical Wnt signaling pathway	0.0446	23	1221	51	-0.28	0.098	1000	-1000	-0.049	-1000
Noncanonical Wnt signaling pathway	0.0426	22	593	26	-0.11	0.014	1000	-1000	-0.055	-1000
Syndecan-3-mediated signaling events	0.0426	22	783	35	-0.16	0.014	1000	-1000	-0.055	-1000
Integrins in angiogenesis	0.0426	22	1902	84	-0.093	0.014	1000	-1000	-0.078	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0426	22	1636	74	-0.16	0.063	1000	-1000	-0.075	-1000
Signaling events mediated by PTP1B	0.0407	21	1669	76	-0.14	0.02	1000	-1000	-0.074	-1000
S1P1 pathway	0.0388	20	731	36	-0.1	0.014	1000	-1000	-0.05	-1000
TCGA08_rtk_signaling	0.0388	20	532	26	-0.15	0.028	1000	-1000	-0.018	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0388	20	1606	78	-0.062	0.04	1000	-1000	-0.062	-1000
Aurora A signaling	0.0368	19	1141	60	-0.14	0.032	1000	-1000	-0.055	-1000
Ephrin B reverse signaling	0.0368	19	939	48	-0.1	0.078	1000	-1000	-0.063	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0349	18	510	28	-0.13	0.024	1000	-1000	-0.034	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0349	18	1545	83	-0.19	0.053	1000	-1000	-0.068	-1000
ErbB4 signaling events	0.0329	17	1240	69	-0.15	0.041	1000	-1000	-0.082	-1000
Ceramide signaling pathway	0.0329	17	1346	76	-0.15	0.022	1000	-1000	-0.055	-1000
EPHB forward signaling	0.0329	17	1452	85	-0.1	0.035	1000	-1000	-0.087	-1000
TRAIL signaling pathway	0.0310	16	792	48	-0.046	0.03	1000	-1000	-0.067	-1000
Signaling mediated by p38-gamma and p38-delta	0.0310	16	246	15	-0.026	0.027	1000	-1000	-0.02	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0310	16	737	45	-0.15	0.032	1000	-1000	-0.081	-1000
Regulation of Telomerase	0.0310	16	1677	102	-0.14	0.045	1000	-1000	-0.1	-1000
S1P4 pathway	0.0310	16	411	25	-0.13	0.03	1000	-1000	-0.055	-1000
Insulin-mediated glucose transport	0.0291	15	511	32	-0.11	0.034	1000	-1000	-0.056	-1000
Plasma membrane estrogen receptor signaling	0.0291	15	1341	86	-0.058	0.033	1000	-1000	-0.067	-1000
BARD1 signaling events	0.0271	14	827	57	-0.053	0.03	1000	-1000	-0.059	-1000
Paxillin-dependent events mediated by a4b1	0.0271	14	526	36	-0.14	0.031	1000	-1000	-0.063	-1000
Regulation of p38-alpha and p38-beta	0.0271	14	791	54	-0.11	0.014	1000	-1000	-0.055	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0271	14	464	33	-0.1	0.041	1000	-1000	-0.056	-1000
E-cadherin signaling in keratinocytes	0.0271	14	632	43	-0.12	0.026	1000	-1000	-0.062	-1000
Regulation of Androgen receptor activity	0.0271	14	1003	70	-0.13	0.031	1000	-1000	-0.067	-1000
Atypical NF-kappaB pathway	0.0233	12	391	31	-0.081	0.029	1000	-1000	-0.033	-1000
p38 MAPK signaling pathway	0.0233	12	558	44	-0.072	0.02	1000	-1000	-0.057	-1000
EPO signaling pathway	0.0213	11	623	55	-0.11	0.057	1000	-1000	-0.081	-1000
Nectin adhesion pathway	0.0213	11	723	63	-0.12	0.048	1000	-1000	-0.074	-1000
ceramide signaling pathway	0.0213	11	581	49	-0.15	0.02	1000	-1000	-0.049	-1000
Class I PI3K signaling events	0.0213	11	837	73	-0.1	0.03	1000	-1000	-0.063	-1000
Canonical NF-kappaB pathway	0.0194	10	403	39	-0.15	0.086	1000	-1000	-0.082	-1000
IFN-gamma pathway	0.0194	10	680	68	-0.23	0.058	1000	-1000	-0.084	-1000
Signaling events mediated by PRL	0.0194	10	345	34	-0.063	0.021	1000	-1000	-0.034	-1000
Circadian rhythm pathway	0.0174	9	200	22	-0.018	0.033	1000	-1000	-0.042	-1000
S1P3 pathway	0.0174	9	385	42	-0.032	0.031	1000	-1000	-0.039	-1000
Class IB PI3K non-lipid kinase events	0.0174	9	27	3	-0.004	0.004	1000	-1000	-0.007	-1000
HIF-2-alpha transcription factor network	0.0155	8	355	43	-0.098	0.099	1000	-1000	-0.073	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0155	8	1056	125	-0.073	0.075	1000	-1000	-0.086	-1000
VEGFR1 specific signals	0.0155	8	501	56	-0.092	0.04	1000	-1000	-0.067	-1000
Hedgehog signaling events mediated by Gli proteins	0.0136	7	468	65	-0.042	0.064	1000	-1000	-0.054	-1000
Signaling events mediated by HDAC Class I	0.0136	7	779	104	-0.15	0.058	1000	-1000	-0.064	-1000
Insulin Pathway	0.0136	7	552	74	-0.18	0.038	1000	-1000	-0.076	-1000
PDGFR-beta signaling pathway	0.0136	7	703	97	-0.054	0.063	1000	-1000	-0.07	-1000
Signaling events mediated by HDAC Class II	0.0116	6	458	75	-0.18	0.038	1000	-1000	-0.058	-1000
IGF1 pathway	0.0116	6	361	57	-0.049	0.053	1000	-1000	-0.079	-1000
Class I PI3K signaling events mediated by Akt	0.0097	5	372	68	-0.11	0.054	1000	-1000	-0.049	-1000
FoxO family signaling	0.0097	5	346	64	-0.11	0.12	1000	-1000	-0.064	-1000
Arf6 trafficking events	0.0097	5	389	71	-0.11	0.047	1000	-1000	-0.063	-1000
Arf6 downstream pathway	0.0078	4	182	43	-0.027	0.028	1000	-1000	-0.038	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0039	2	51	23	-0.014	0.05	1000	-1000	-0.059	-1000
Alternative NF-kappaB pathway	0.0039	2	28	13	-0.005	0.014	1000	-1000	-0.058	-1000
mTOR signaling pathway	0.0019	1	87	53	-0.005	0.036	1000	-1000	-0.055	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	26	27	-0.004	0.036	1000	-1000	-0.046	-1000
Arf1 pathway	0.0000	0	26	54	-0.004	0.037	1000	-1000	-0.044	-1000
Total	NA	4096	223393	7203	-20	5.5	131000	-131000	-8	-131000

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.15	0.22	-9999	-0.44	173	173
EFNA5	-0.085	0.22	-9999	-0.55	91	91
FYN	-0.11	0.22	-9999	-0.39	173	173
neuron projection morphogenesis	-0.15	0.22	-9999	-0.44	173	173
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.15	0.22	-9999	-0.44	173	173
EPHA5	-0.14	0.25	-9999	-0.55	141	141

×

IL23-mediated signaling events

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
CCL2	-0.58	0.56	-10000	0	-1.2	184	184
IL23A	-0.6	0.56	-10000	0	-1.2	183	183
NF kappa B1 p50/RelA/I kappa B alpha	-0.57	0.51	-10000	0	-1.1	195	195
positive regulation of T cell mediated cytotoxicity	-0.62	0.62	-10000	0	-1.3	195	195
ITGA3	-0.55	0.52	-10000	0	-1.1	176	176
IL17F	-0.35	0.33	-10000	0	-0.74	149	149
IL12B	-0.023	0.064	-10000	0	-0.54	6	6
STAT1 (dimer)	-0.6	0.59	-10000	0	-1.2	197	197
CD4	-0.53	0.5	-10000	0	-1.1	178	178
IL23	-0.58	0.53	-10000	0	-1.2	184	184
IL23R	-0.082	0.084	-10000	0	-10000	0	0
IL1B	-0.64	0.61	-10000	0	-1.3	199	199
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.53	0.5	-10000	0	-1.1	172	172
TYK2	-0.001	0.018	-10000	0	-10000	0	0
STAT4	-0.16	0.26	-10000	0	-0.53	166	166
STAT3	0.014	0	-10000	0	-10000	0	0
IL18RAP	-0.077	0.21	-10000	0	-0.54	85	85
IL12RB1	-0.047	0.16	-10000	0	-0.59	41	41
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
IL12Rbeta1/TYK2	-0.038	0.12	-10000	0	-0.44	41	41
IL23R/JAK2	-0.092	0.1	-10000	0	-10000	0	0
positive regulation of chronic inflammatory response	-0.62	0.62	-10000	0	-1.3	195	195
natural killer cell activation	0.008	0.007	0.047	1	-10000	0	1
JAK2	0.008	0.018	-10000	0	-10000	0	0
PIK3R1	0.014	0	-10000	0	-10000	0	0
NFKB1	0.011	0.003	-10000	0	-10000	0	0
RELA	0.011	0.003	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.55	0.5	-10000	0	-1.1	187	187
ALOX12B	-0.6	0.56	-10000	0	-1.2	206	206
CXCL1	-0.59	0.55	-10000	0	-1.2	185	185
T cell proliferation	-0.62	0.62	-10000	0	-1.3	195	195
NFKBIA	0.011	0.003	-10000	0	-10000	0	0
IL17A	-0.26	0.26	-10000	0	-0.58	118	118
PI3K	-0.58	0.52	-10000	0	-1.2	198	198
IFNG	-0.023	0.031	-10000	0	-0.1	7	7
STAT3 (dimer)	-0.55	0.48	-10000	0	-1.1	194	194
IL18R1	-0.049	0.18	-10000	0	-0.54	60	60
IL23/IL23R/JAK2/TYK2/SOCS3	-0.32	0.3	-10000	0	-0.67	129	129
IL18/IL18R	-0.092	0.21	-10000	0	-0.45	99	99
macrophage activation	-0.027	0.018	-10000	0	-0.045	151	151
TNF	-0.63	0.6	-10000	0	-1.3	186	186
STAT3/STAT4	-0.64	0.53	-10000	0	-1.2	222	222
STAT4 (dimer)	-0.66	0.59	-10000	0	-1.2	218	218
IL18	-0.029	0.15	-10000	0	-0.54	41	41
IL19	-0.53	0.5	-10000	0	-1.1	170	170
STAT5A (dimer)	-0.6	0.59	-10000	0	-1.2	193	193
STAT1	-0.001	0.087	-10000	0	-0.49	16	16
SOCS3	-0.11	0.23	-10000	0	-0.52	124	124
CXCL9	-0.62	0.56	-10000	0	-1.2	221	221
MPO	-0.62	0.56	-10000	0	-1.2	202	202
positive regulation of humoral immune response	-0.62	0.62	-10000	0	-1.3	195	195
IL23/IL23R/JAK2/TYK2	-0.68	0.72	-10000	0	-1.4	195	195
IL6	-0.6	0.56	-10000	0	-1.2	196	196
STAT5A	0.001	0.088	-10000	0	-0.59	11	11
IL2	0.006	0.006	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0.008	0.007	0.047	1	-10000	0	1
CD3E	-0.61	0.56	-10000	0	-1.2	190	190
keratinocyte proliferation	-0.62	0.62	-10000	0	-1.3	195	195
NOS2	-0.55	0.53	-10000	0	-1.2	164	164

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.21	0.64	-10000	0	-1.2	129	129
PLK1	-0.006	0.2	-10000	0	-1.5	5	5
BIRC5	-0.22	0.54	-10000	0	-1.1	123	123
HSPA1B	-0.23	0.66	-10000	0	-1.2	134	134
MAP2K1	0.022	0.056	-10000	0	-0.54	2	2
BRCA2	-0.23	0.67	-10000	0	-1.2	138	138
FOXM1	-0.36	0.92	-10000	0	-1.7	139	139
XRCC1	-0.21	0.64	-10000	0	-1.2	132	132
FOXM1B/p19	-0.38	0.56	0.43	6	-1.2	138	144
Cyclin D1/CDK4	-0.2	0.6	-10000	0	-1.1	138	138
CDC2	-0.23	0.68	-10000	0	-1.2	139	139
TGFA	-0.18	0.58	-10000	0	-1	140	140
SKP2	-0.22	0.65	-10000	0	-1.2	135	135
CCNE1	0.012	0.041	-10000	0	-0.5	3	3
CKS1B	-0.21	0.64	-10000	0	-1.2	128	128
RB1	-0.17	0.27	-10000	0	-0.73	65	65
FOXM1C/SP1	-0.29	0.75	-10000	0	-1.4	140	140
AURKB	-0.27	0.57	-10000	0	-1.5	91	91
CENPF	-0.24	0.7	-10000	0	-1.3	135	135
CDK4	0.002	0.091	-10000	0	-0.5	16	16
MYC	-0.18	0.57	-10000	0	-1	134	134
CHEK2	0.007	0.11	-10000	0	-0.56	16	16
ONECUT1	-0.22	0.63	-10000	0	-1.1	141	141
CDKN2A	-0.1	0.23	-10000	0	-0.56	104	104
LAMA4	-0.21	0.64	-10000	0	-1.2	132	132
FOXM1B/HNF6	-0.3	0.78	-10000	0	-1.5	141	141
FOS	-0.3	0.7	-10000	0	-1.2	174	174
SP1	0.014	0.006	-10000	0	-10000	0	0
CDC25B	-0.21	0.64	-10000	0	-1.2	131	131
response to radiation	0.008	0.041	-10000	0	-10000	0	0
CENPB	-0.21	0.64	-10000	0	-1.2	131	131
CENPA	-0.26	0.7	-10000	0	-1.3	143	143
NEK2	-0.28	0.72	-10000	0	-1.3	147	147
HIST1H2BA	-0.22	0.64	-10000	0	-1.2	127	127
CCNA2	-0.054	0.19	-10000	0	-0.54	66	66
EP300	0.009	0.053	-10000	0	-0.59	4	4
CCNB1/CDK1	-0.29	0.77	-10000	0	-1.5	135	135
CCNB2	-0.28	0.74	-10000	0	-1.4	145	145
CCNB1	-0.24	0.69	-10000	0	-1.3	135	135
ETV5	-0.23	0.65	-10000	0	-1.2	138	138
ESR1	-0.23	0.65	-10000	0	-1.2	142	142
CCND1	-0.2	0.61	-10000	0	-1.1	139	139
GSK3A	0.025	0.036	-10000	0	-10000	0	0
Cyclin A-E1/CDK1-2	-0.015	0.16	-10000	0	-0.39	69	69
CDK2	0.001	0.089	-10000	0	-0.54	13	13
G2/M transition of mitotic cell cycle	0.008	0.049	-10000	0	-10000	0	0
FOXM1B/Cbp/p300	-0.41	0.58	-10000	0	-1.3	145	145
GAS1	-0.22	0.65	-10000	0	-1.2	134	134
MMP2	-0.22	0.65	-10000	0	-1.2	128	128
RB1/FOXM1C	-0.22	0.64	-10000	0	-1.2	137	137
CREBBP	0.014	0	-10000	0	-10000	0	0

×

TCGA08_retinoblastoma

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
CDKN2B	-0.06	0.19	-10000	0	-0.54	69	69
CDKN2C	-0.022	0.13	-10000	0	-0.44	46	46
CDKN2A	-0.097	0.22	-10000	0	-0.54	104	104
CCND2	0.064	0.14	0.3	109	-0.14	2	111
RB1	-0.068	0.15	-10000	0	-0.32	106	106
CDK4	0.075	0.15	0.34	107	-10000	0	107
CDK6	0.068	0.16	0.33	109	-0.16	15	124
G1/S progression	0.055	0.15	0.32	106	-10000	0	106

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.12	0.17	-10000	0	-0.4	91	91
TBX21	-0.47	0.5	-10000	0	-1	192	192
B2M	0.009	0.05	-10000	0	-0.49	5	5
TYK2	0.001	0.019	-10000	0	-10000	0	0
IL12RB1	-0.045	0.16	-10000	0	-0.58	41	41
GADD45B	-0.35	0.39	-10000	0	-0.84	141	141
IL12RB2	-0.13	0.24	-10000	0	-0.54	126	126
GADD45G	-0.36	0.41	-10000	0	-0.83	169	169
natural killer cell activation	-0.016	0.023	-10000	0	-10000	0	0
RELB	0.009	0.052	-10000	0	-0.51	5	5
RELA	0.014	0	-10000	0	-10000	0	0
IL18	-0.033	0.15	-10000	0	-0.56	41	41
IL2RA	-0.063	0.18	-10000	0	-0.5	73	73
IFNG	-0.002	0.049	-10000	0	-0.49	5	5
STAT3 (dimer)	-0.36	0.36	-10000	0	-0.74	204	204
HLA-DRB5	-0.13	0.24	-10000	0	-0.54	130	130
FASLG	-0.44	0.46	-10000	0	-0.96	190	190
NF kappa B2 p52/RelB	-0.46	0.43	-10000	0	-0.89	216	216
CD4	0.005	0.062	-10000	0	-0.52	7	7
SOCS1	-0.031	0.15	-10000	0	-0.51	45	45
EntrezGene:6955	-0.002	0.008	-10000	0	-10000	0	0
CD3D	-0.11	0.23	-10000	0	-0.53	115	115
CD3E	-0.13	0.24	-10000	0	-0.54	137	137
CD3G	-0.034	0.14	-10000	0	-0.5	43	43
IL12Rbeta2/JAK2	-0.097	0.18	-10000	0	-0.4	126	126
CCL3	-0.56	0.58	-10000	0	-1.1	220	220
CCL4	-0.56	0.59	-10000	0	-1.2	202	202
HLA-A	0.005	0.07	-10000	0	-0.49	10	10
IL18/IL18R	-0.091	0.22	-10000	0	-0.42	139	139
NOS2	-0.41	0.45	-10000	0	-0.93	170	170
IL12/IL12R/TYK2/JAK2/SPHK2	-0.1	0.15	-10000	0	-0.38	75	75
IL1R1	-0.45	0.48	-10000	0	-0.99	187	187
IL4	0.019	0.023	-10000	0	-10000	0	0
JAK2	0.001	0.019	-10000	0	-10000	0	0
EntrezGene:6957	-0.002	0.008	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.12	0.23	-10000	0	-0.55	89	89
RAB7A	-0.28	0.32	-10000	0	-0.7	129	129
lysosomal transport	-0.27	0.3	-10000	0	-0.66	130	130
FOS	-0.36	0.46	-10000	0	-0.96	147	147
STAT4 (dimer)	-0.42	0.41	-10000	0	-0.84	209	209
STAT5A (dimer)	-0.46	0.44	-10000	0	-0.89	221	221
GZMA	-0.52	0.54	-10000	0	-1.1	211	211
GZMB	-0.5	0.52	-10000	0	-1.1	195	195
HLX	-0.002	0.092	-10000	0	-0.52	16	16
LCK	-0.51	0.53	-10000	0	-1	231	231
TCR/CD3/MHC II/CD4	-0.16	0.25	-10000	0	-0.5	142	142
IL2/IL2R	-0.12	0.21	-10000	0	-0.47	104	104
MAPK14	-0.35	0.39	-10000	0	-0.8	174	174
CCR5	-0.4	0.45	-10000	0	-0.98	143	143
IL1B	-0.19	0.27	-10000	0	-0.56	174	174
STAT6	-0.11	0.12	-10000	0	-0.3	5	5
STAT4	-0.16	0.26	-10000	0	-0.53	166	166
STAT3	0.014	0	-10000	0	-10000	0	0
STAT1	-0.001	0.087	-10000	0	-0.49	16	16
NFKB1	0.014	0	-10000	0	-10000	0	0
NFKB2	0.011	0.044	-10000	0	-0.56	3	3
IL12B	-0.016	0.06	-10000	0	-0.53	6	6
CD8A	-0.077	0.21	-10000	0	-0.55	85	85
CD8B	-0.032	0.16	-10000	0	-0.56	42	42
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.12	0.17	0.39	91	-10000	0	91
IL2RB	-0.095	0.22	-10000	0	-0.53	103	103
proteasomal ubiquitin-dependent protein catabolic process	-0.38	0.36	-10000	0	-0.76	207	207
IL2RG	-0.041	0.16	-10000	0	-0.52	53	53
IL12	-0.035	0.11	-10000	0	-0.44	35	35
STAT5A	0.001	0.088	-10000	0	-0.59	11	11
CD247	-0.02	0.13	-10000	0	-0.52	31	31
IL2	0.001	0.003	-10000	0	-10000	0	0
SPHK2	0.014	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.032	0.14	-10000	0	-0.6	29	29
IL12/IL12R/TYK2/JAK2	-0.52	0.57	-10000	0	-1	225	225
MAP2K3	-0.36	0.4	-10000	0	-0.78	188	188
RIPK2	0.014	0	-10000	0	-10000	0	0
MAP2K6	-0.36	0.4	-10000	0	-0.78	188	188
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.09	0.22	-10000	0	-0.54	96	96
IL18RAP	-0.081	0.21	-10000	0	-0.55	85	85
IL12Rbeta1/TYK2	-0.034	0.12	-10000	0	-0.43	41	41
EOMES	-0.002	0.13	-10000	0	-1.3	1	1
STAT1 (dimer)	-0.36	0.35	-10000	0	-0.73	198	198
T cell proliferation	-0.31	0.29	-10000	0	-0.61	196	196
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.053	0.18	-10000	0	-0.55	60	60
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.36	0.29	-10000	0	-0.67	200	200
ATF2	-0.33	0.36	-10000	0	-0.75	164	164

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.13	0.26	-9999	-0.56	116	116
STMN1	-0.1	0.2	-9999	-0.4	158	158
Aurora B/RasGAP/Survivin	-0.17	0.28	-9999	-0.55	170	170
Chromosomal passenger complex/Cul3 protein complex	-0.093	0.2	-9999	-0.37	147	147
BIRC5	-0.14	0.26	-9999	-0.57	138	138
DES	-0.34	0.45	-9999	-0.92	167	167
Aurora C/Aurora B/INCENP	-0.1	0.17	-9999	-0.32	178	178
Aurora B/TACC1	-0.094	0.16	-9999	-0.33	157	157
Aurora B/PP2A	-0.11	0.19	-9999	-0.4	157	157
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.028	0.074	-9999	-0.17	92	92
mitotic metaphase/anaphase transition	0	0.006	-9999	-10000	0	0
NDC80	-0.2	0.32	-9999	-0.6	182	182
Cul3 protein complex	-0.008	0.052	-9999	-0.36	11	11
KIF2C	-0.13	0.27	-9999	-0.44	170	170
PEBP1	0.005	0.055	-9999	-0.61	4	4
KIF20A	-0.17	0.27	-9999	-0.55	169	169
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.11	0.19	-9999	-0.4	157	157
SEPT1	0.009	0.052	-9999	-0.51	5	5
SMC2	0.014	0	-9999	-10000	0	0
SMC4	-0.015	0.12	-9999	-0.49	30	30
NSUN2/NPM1/Nucleolin	-0.16	0.32	-9999	-0.83	91	91
PSMA3	0.014	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.004	-9999	-10000	0	0
H3F3B	-0.075	0.15	-9999	-0.29	157	157
AURKB	-0.16	0.27	-9999	-0.56	157	157
AURKC	-0.021	0.13	-9999	-0.52	34	34
CDCA8	-0.062	0.19	-9999	-0.53	70	70
cytokinesis	-0.27	0.4	-9999	-0.78	172	172
Aurora B/Septin1	-0.24	0.38	-9999	-0.75	166	166
AURKA	-0.015	0.12	-9999	-0.5	29	29
INCENP	0.008	0.029	-9999	-0.62	1	1
KLHL13	0.012	0.038	-9999	-0.59	2	2
BUB1	-0.11	0.24	-9999	-0.55	119	119
hSgo1/Aurora B/Survivin	-0.23	0.35	-9999	-0.66	190	190
EVI5	0.013	0.003	-9999	-10000	0	0
RhoA/GTP	-0.24	0.35	-9999	-0.71	162	162
SGOL1	-0.12	0.24	-9999	-0.54	127	127
CENPA	-0.17	0.32	-9999	-0.57	165	165
NCAPG	-0.14	0.25	-9999	-0.55	142	142
Aurora B/HC8 Proteasome	-0.11	0.19	-9999	-0.4	157	157
NCAPD2	0.009	0.049	-9999	-0.49	5	5
Aurora B/PP1-gamma	-0.11	0.19	-9999	-0.4	157	157
RHOA	0.014	0	-9999	-10000	0	0
NCAPH	-0.065	0.19	-9999	-0.54	74	74
NPM1	-0.13	0.24	-9999	-0.62	91	91
RASA1	0.014	0	-9999	-10000	0	0
KLHL9	0.004	0.079	-9999	-0.59	9	9
mitotic prometaphase	-0.006	0.01	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.11	0.19	-9999	-0.39	157	157
PPP1CC	0.014	0	-9999	-10000	0	0
Centraspindlin	-0.26	0.39	-9999	-0.76	174	174
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.13	0.24	-9999	-0.62	91	91
MYLK	-0.086	0.16	-9999	-0.3	171	171
KIF23	-0.11	0.23	-9999	-0.54	113	113
VIM	-0.16	0.24	-9999	-0.43	214	214
RACGAP1	0.004	0.057	-9999	-0.52	6	6
mitosis	0	0	-9999	-10000	0	0
NCL	-0.13	0.24	-9999	-0.62	91	91
Chromosomal passenger complex	-0.21	0.38	-9999	-0.68	171	171
Chromosomal passenger complex/EVI5	-0.18	0.31	-9999	-0.58	172	172
TACC1	0.014	0	-9999	-10000	0	0
PPP2R5D	0.014	0	-9999	-10000	0	0
CUL3	0.014	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	-0.012	0.1	-10000	0	-0.57	12	12
NFATC2	-0.13	0.3	-10000	0	-0.68	95	95
NFATC3	-0.049	0.11	-10000	0	-0.31	12	12
CD40LG	-0.38	0.49	-10000	0	-1	157	157
ITCH	-0.031	0.12	-10000	0	-0.52	3	3
CBLB	-0.033	0.13	-10000	0	-0.6	4	4
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.33	0.4	-10000	0	-0.94	118	118
JUNB	-0.031	0.15	-10000	0	-0.52	44	44
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.084	0.12	-10000	0	-0.61	3	3
T cell anergy	-0.096	0.19	-10000	0	-0.43	90	90
TLE4	-0.08	0.25	-10000	0	-0.65	57	57
Jun/NFAT1-c-4/p21SNFT	-0.36	0.46	-10000	0	-0.99	143	143
AP-1/NFAT1-c-4	-0.46	0.6	-10000	0	-1.2	157	157
IKZF1	-0.091	0.28	-10000	0	-0.72	60	60
T-helper 2 cell differentiation	-0.18	0.3	-10000	0	-0.72	82	82
AP-1/NFAT1	-0.17	0.26	-10000	0	-0.55	129	129
CALM1	-0.026	0.088	-10000	0	-0.69	2	2
EGR2	-0.31	0.57	-10000	0	-1.1	122	122
EGR3	-0.34	0.6	-10000	0	-1.2	130	130
NFAT1/FOXP3	-0.12	0.25	-10000	0	-0.61	80	80
EGR1	-0.11	0.23	-10000	0	-0.54	114	114
JUN	-0.003	0.077	-10000	0	-0.51	11	11
EGR4	-0.19	0.27	-10000	0	-0.55	187	187
mol:Ca2+	-0.041	0.083	-10000	0	-0.3	1	1
GBP3	-0.16	0.35	-10000	0	-0.74	112	112
FOSL1	-0.093	0.22	-10000	0	-0.53	101	101
NFAT1-c-4/MAF/IRF4	-0.33	0.45	-10000	0	-0.97	135	135
DGKA	-0.073	0.23	-10000	0	-0.6	55	55
CREM	0.012	0.035	-10000	0	-0.54	2	2
NFAT1-c-4/PPARG	-0.34	0.46	-10000	0	-0.97	145	145
CTLA4	-0.12	0.29	-10000	0	-0.67	93	93
NFAT1-c-4 (dimer)/EGR1	-0.38	0.53	-10000	0	-1.1	162	162
NFAT1-c-4 (dimer)/EGR4	-0.43	0.49	-10000	0	-1	170	170
FOS	-0.1	0.23	-10000	0	-0.56	101	101
IFNG	-0.17	0.24	-10000	0	-0.78	42	42
T cell activation	-0.17	0.29	-10000	0	-0.78	49	49
MAF	0.011	0.046	-10000	0	-0.59	3	3
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.23	0.42	0.82	131	-10000	0	131
TNF	-0.48	0.51	-10000	0	-1	202	202
FASLG	-0.35	0.57	-10000	0	-1.2	121	121
TBX21	-0.044	0.17	-10000	0	-0.53	56	56
BATF3	-0.034	0.16	-10000	0	-0.53	45	45
PRKCQ	-0.005	0.11	-10000	0	-0.58	17	17
PTPN1	-0.073	0.23	-10000	0	-0.6	55	55
NFAT1-c-4/ICER1	-0.32	0.46	-10000	0	-0.96	143	143
GATA3	-0.11	0.23	-10000	0	-0.54	115	115
T-helper 1 cell differentiation	-0.16	0.25	-10000	0	-0.74	46	46
IL2RA	-0.3	0.34	-10000	0	-0.83	110	110
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.074	0.23	-10000	0	-0.57	65	65
E2F1	-0.01	0.12	-10000	0	-0.52	28	28
PPARG	-0.014	0.12	-10000	0	-0.56	25	25
SLC3A2	-0.073	0.23	-10000	0	-0.57	64	64
IRF4	-0.043	0.17	-10000	0	-0.54	53	53
PTGS2	-0.41	0.53	-10000	0	-1.1	162	162
CSF2	-0.37	0.48	-10000	0	-1	148	148
JunB/Fra1/NFAT1-c-4	-0.37	0.47	-10000	0	-0.97	158	158
IL4	-0.19	0.31	-10000	0	-0.76	81	81
IL5	-0.37	0.48	-10000	0	-1	149	149
IL2	-0.17	0.29	-10000	0	-0.8	48	48
IL3	-0.064	0.064	-10000	0	-0.55	1	1
RNF128	-0.15	0.29	-10000	0	-0.55	172	172
NFATC1	-0.23	0.43	-10000	0	-0.83	130	130
CDK4	0.13	0.24	0.67	28	-10000	0	28
PTPRK	-0.075	0.23	-10000	0	-0.6	61	61
IL8	-0.43	0.53	-10000	0	-1.1	178	178
POU2F1	0.013	0.027	-10000	0	-0.59	1	1

×

Syndecan-1-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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.004	0.079	-9999	-0.59	9	9
CCL5	-0.086	0.21	-9999	-0.53	94	94
SDCBP	0.014	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.13	0.19	-9999	-0.37	137	137
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.12	0.18	-9999	-0.45	77	77
Syndecan-1/Syntenin	-0.12	0.18	-9999	-0.45	75	75
MAPK3	-0.095	0.16	-9999	-0.47	44	44
HGF/MET	-0.17	0.22	-9999	-0.43	204	204
TGFB1/TGF beta receptor Type II	0.004	0.079	-9999	-0.59	9	9
BSG	0.014	0	-9999	-10000	0	0
keratinocyte migration	-0.12	0.18	-9999	-0.44	77	77
Syndecan-1/RANTES	-0.17	0.22	-9999	-0.46	137	137
Syndecan-1/CD147	-0.11	0.17	-9999	-0.43	75	75
Syndecan-1/Syntenin/PIP2	-0.12	0.16	-9999	-0.43	75	75
LAMA5	0.012	0.035	-9999	-0.54	2	2
positive regulation of cell-cell adhesion	-0.13	0.15	-9999	-0.42	75	75
MMP7	-0.16	0.26	-9999	-0.54	155	155
HGF	-0.079	0.2	-9999	-0.51	91	91
Syndecan-1/CASK	-0.13	0.18	-9999	-0.36	137	137
Syndecan-1/HGF/MET	-0.23	0.25	-9999	-0.51	181	181
regulation of cell adhesion	-0.084	0.16	-9999	-0.45	43	43
HPSE	-0.052	0.18	-9999	-0.56	59	59
positive regulation of cell migration	-0.13	0.19	-9999	-0.37	137	137
SDC1	-0.14	0.19	-9999	-0.38	137	137
Syndecan-1/Collagen	-0.13	0.19	-9999	-0.37	137	137
PPIB	0.014	0	-9999	-10000	0	0
MET	-0.15	0.25	-9999	-0.54	151	151
PRKACA	0.014	0	-9999	-10000	0	0
MMP9	-0.14	0.24	-9999	-0.52	144	144
MAPK1	-0.095	0.16	-9999	-0.47	44	44
homophilic cell adhesion	-0.13	0.18	-9999	-0.37	137	137
MMP1	-0.047	0.16	-9999	-0.49	56	56

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.083	0.15	-9999	-0.32	132	132
E-cadherin/beta catenin	-0.093	0.17	-9999	-0.38	125	125
CTNNB1	0.014	0	-9999	-10000	0	0
JUP	0.003	0.081	-9999	-0.57	10	10
CDH1	-0.12	0.24	-9999	-0.54	125	125

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	-0.049	0.14	-9999	-0.36	85	85
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.093	0.17	-9999	-0.4	120	120
STXBP1	-0.014	0.12	-9999	-0.5	28	28
ACh/CHRNA1	-0.13	0.17	-9999	-0.37	163	163
RAB3GAP2/RIMS1/UNC13B	-0.077	0.14	-9999	-0.36	76	76
mol:Ca2+	0	0	-9999	-10000	0	0
UniProt:P30996	0	0	-9999	-10000	0	0
UniProt:Q60393	0	0	-9999	-10000	0	0
CST086	0	0	-9999	-10000	0	0
RIMS1	-0.12	0.24	-9999	-0.56	120	120
mol:ACh	-0.038	0.068	-9999	-0.13	165	165
RAB3GAP2	0.014	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.14	0.2	-9999	-0.45	130	130
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.13	0.17	-9999	-0.37	163	163
UNC13B	0.013	0.027	-9999	-0.59	1	1
CHRNA1	-0.16	0.26	-9999	-0.53	162	162
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.16	0.21	-9999	-0.41	200	200
SNAP25	-0.075	0.13	-9999	-0.25	168	168
VAMP2	0.007	0	-9999	-10000	0	0
SYT1	-0.2	0.27	-9999	-0.54	200	200
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.047	0.16	-9999	-0.38	87	87
STX1A/SNAP25 fragment 1/VAMP2	-0.14	0.2	-9999	-0.45	130	130

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.14	0.18	-10000	0	-0.45	106	106
FYN	-0.14	0.27	-10000	0	-0.54	130	130
LAT/GRAP2/SLP76	-0.16	0.22	-10000	0	-0.49	127	127
IKBKB	0.014	0	-10000	0	-10000	0	0
AKT1	-0.1	0.19	-10000	0	-0.38	123	123
B2M	0.007	0.051	-10000	0	-0.5	5	5
IKBKG	-0.034	0.046	-10000	0	-0.14	31	31
MAP3K8	-0.005	0.099	-10000	0	-0.51	19	19
mol:Ca2+	-0.025	0.042	-10000	0	-0.11	91	91
integrin-mediated signaling pathway	-0.01	0.058	-10000	0	-0.33	16	16
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.15	0.26	-10000	0	-0.53	132	132
TRPV6	-0.11	0.23	-10000	0	-0.56	105	105
CD28	-0.075	0.2	-10000	0	-0.54	81	81
SHC1	-0.14	0.26	-10000	0	-0.53	129	129
receptor internalization	-0.13	0.23	-10000	0	-0.48	122	122
PRF1	-0.17	0.36	-10000	0	-0.9	78	78
KRAS	0.013	0.022	-10000	0	-0.49	1	1
GRB2	0.013	0.022	-10000	0	-0.49	1	1
COT/AKT1	-0.081	0.16	-10000	0	-0.33	115	115
LAT	-0.16	0.26	-10000	0	-0.52	136	136
EntrezGene:6955	-0.002	0.006	-10000	0	-10000	0	0
CD3D	-0.11	0.23	-10000	0	-0.53	115	115
CD3E	-0.13	0.25	-10000	0	-0.54	137	137
CD3G	-0.034	0.14	-10000	0	-0.5	43	43
RASGRP2	-0.006	0.025	-10000	0	-0.18	3	3
RASGRP1	-0.11	0.2	-10000	0	-0.39	131	131
HLA-A	0.002	0.071	-10000	0	-0.5	10	10
RASSF5	-0.003	0.098	-10000	0	-0.55	16	16
RAP1A/GTP/RAPL	-0.01	0.058	-10000	0	-0.33	16	16
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	-0.015	0.062	-10000	0	-0.11	68	68
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.063	0.08	-10000	0	-0.22	71	71
PRKCA	-0.078	0.1	-10000	0	-0.25	94	94
GRAP2	-0.047	0.17	-10000	0	-0.53	58	58
mol:IP3	-0.1	0.19	0.22	48	-0.38	113	161
EntrezGene:6957	-0.002	0.006	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.11	0.21	-10000	0	-0.44	116	116
ORAI1	0.067	0.12	0.31	104	-0.36	1	105
CSK	-0.15	0.26	-10000	0	-0.53	129	129
B7 family/CD28	-0.21	0.27	-10000	0	-0.57	148	148
CHUK	0.014	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.17	0.29	-10000	0	-0.57	141	141
PTPN6	-0.15	0.27	-10000	0	-0.55	135	135
VAV1	-0.16	0.27	-10000	0	-0.55	133	133
Monovalent TCR/CD3	-0.11	0.19	-10000	0	-0.36	170	170
CBL	0.014	0	-10000	0	-10000	0	0
LCK	-0.17	0.29	-10000	0	-0.55	151	151
PAG1	-0.15	0.26	-10000	0	-0.53	129	129
RAP1A	0.014	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.17	0.29	-10000	0	-0.58	137	137
CD80	-0.046	0.16	-10000	0	-0.51	56	56
CD86	-0.027	0.15	-10000	0	-0.56	36	36
PDK1/CARD11/BCL10/MALT1	-0.077	0.097	-10000	0	-0.26	79	79
HRAS	0.014	0	-10000	0	-10000	0	0
GO:0035030	-0.15	0.25	-10000	0	-0.48	145	145
CD8A	-0.08	0.21	-10000	0	-0.55	85	85
CD8B	-0.035	0.16	-10000	0	-0.56	42	42
PTPRC	-0.042	0.17	-10000	0	-0.54	51	51
PDK1/PKC theta	-0.12	0.23	-10000	0	-0.46	122	122
CSK/PAG1	-0.14	0.26	-10000	0	-0.53	120	120
SOS1	0.014	0	-10000	0	-10000	0	0
peptide-MHC class I	0.004	0.071	-10000	0	-0.43	12	12
GRAP2/SLP76	-0.18	0.25	-10000	0	-0.54	139	139
STIM1	0.037	0.061	-10000	0	-10000	0	0
RAS family/GTP	-0.022	0.083	-10000	0	-0.17	37	37
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.13	0.25	-10000	0	-0.51	121	121
mol:DAG	-0.11	0.15	-10000	0	-0.34	117	117
RAP1A/GDP	-0.005	0.027	-10000	0	-10000	0	0
PLCG1	0.014	0	-10000	0	-10000	0	0
CD247	-0.019	0.13	-10000	0	-0.52	31	31
cytotoxic T cell degranulation	-0.16	0.34	-10000	0	-0.8	87	87
RAP1A/GTP	-0.004	0.007	-10000	0	-0.067	1	1
mol:PI-3-4-5-P3	-0.13	0.22	-10000	0	-0.44	132	132
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.14	0.23	0.24	36	-0.49	114	150
NRAS	0.014	0	-10000	0	-10000	0	0
ZAP70	-0.046	0.17	-10000	0	-0.53	57	57
GRB2/SOS1	-0.001	0.015	-10000	0	-0.34	1	1
LAT/GRAP2/SLP76/VAV1	-0.16	0.21	-10000	0	-0.48	128	128
MALT1	0.014	0	-10000	0	-10000	0	0
TRAF6	0.013	0.027	-10000	0	-0.59	1	1
CD8 heterodimer	-0.083	0.2	-10000	0	-0.46	108	108
CARD11	-0.009	0.11	-10000	0	-0.57	20	20
PRKCB	-0.1	0.12	-10000	0	-0.27	126	126
PRKCE	-0.082	0.11	-10000	0	-0.26	94	94
PRKCQ	-0.15	0.25	-10000	0	-0.52	127	127
LCP2	-0.001	0.086	-10000	0	-0.5	15	15
BCL10	0.014	0	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.087	0.16	-10000	0	-0.33	121	121
IKK complex	-0.01	0.062	-10000	0	-0.11	29	29
RAS family/GDP	-0.007	0.009	-10000	0	-10000	0	0
MAP3K14	-0.054	0.13	-10000	0	-0.27	77	77
PDPK1	-0.096	0.18	-10000	0	-0.36	119	119
TCR/CD3/MHC I/CD8/Fyn	-0.17	0.3	-10000	0	-0.58	147	147

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.1	0.29	-10000	0	-0.72	65	65
IHH	-0.014	0.086	-10000	0	-0.51	9	9
SHH Np/Cholesterol/GAS1	-0.069	0.16	-10000	0	-0.32	143	143
LRPAP1	0.014	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.086	0.15	0.31	143	-10000	0	143
SMO/beta Arrestin2	-0.036	0.17	-10000	0	-0.66	18	18
SMO	-0.046	0.18	-10000	0	-0.63	24	24
AKT1	0.002	0.083	-10000	0	-0.31	5	5
ARRB2	0.014	0	-10000	0	-10000	0	0
BOC	0.008	0.062	-10000	0	-0.56	6	6
ADRBK1	0.014	0	-10000	0	-10000	0	0
heart looping	-0.045	0.18	-10000	0	-0.61	24	24
STIL	-0.092	0.22	-10000	0	-0.52	74	74
DHH N/PTCH2	-0.058	0.14	-10000	0	-0.4	74	74
DHH N/PTCH1	-0.069	0.19	-10000	0	-0.53	39	39
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
DHH	-0.047	0.17	-10000	0	-0.54	56	56
PTHLH	-0.11	0.34	-10000	0	-0.92	63	63
determination of left/right symmetry	-0.045	0.18	-10000	0	-0.61	24	24
PIK3R1	0.014	0	-10000	0	-10000	0	0
skeletal system development	-0.11	0.34	-10000	0	-0.91	63	63
IHH N/Hhip	-0.12	0.21	-10000	0	-0.45	143	143
DHH N/Hhip	-0.15	0.21	-10000	0	-0.42	180	180
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.045	0.18	-10000	0	-0.61	24	24
pancreas development	-0.14	0.25	-10000	0	-0.55	142	142
HHAT	-0.006	0.11	-10000	0	-0.58	18	18
PI3K	-0.001	0.019	-10000	0	-0.43	1	1
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.014	0.12	-10000	0	-0.5	28	28
somite specification	-0.045	0.18	-10000	0	-0.61	24	24
SHH Np/Cholesterol/PTCH1	-0.093	0.21	-10000	0	-0.53	65	65
SHH Np/Cholesterol/PTCH2	-0.067	0.16	-10000	0	-0.31	142	142
SHH Np/Cholesterol/Megalin	-0.17	0.22	-10000	0	-0.36	259	259
SHH	-0.079	0.19	-10000	0	-0.41	123	123
catabolic process	-0.047	0.18	-10000	0	-0.6	26	26
SMO/Vitamin D3	-0.084	0.22	-10000	0	-0.56	54	54
SHH Np/Cholesterol/Hhip	-0.14	0.21	-10000	0	-0.35	225	225
LRP2	-0.19	0.27	-10000	0	-0.55	187	187
receptor-mediated endocytosis	-0.18	0.22	-10000	0	-0.56	97	97
SHH Np/Cholesterol/BOC	-0.057	0.15	-10000	0	-0.31	126	126
SHH Np/Cholesterol/CDO	-0.075	0.17	-10000	0	-0.33	148	148
mesenchymal cell differentiation	0.15	0.2	0.35	225	-10000	0	225
mol:Vitamin D3	-0.091	0.22	-10000	0	-0.53	65	65
IHH N/PTCH2	-0.011	0.11	-10000	0	-0.45	25	25
CDON	-0.025	0.14	-10000	0	-0.56	35	35
IHH N/PTCH1	-0.047	0.18	-10000	0	-0.6	26	26
Megalin/LRPAP1	-0.14	0.19	-10000	0	-0.39	187	187
PTCH2	-0.009	0.11	-10000	0	-0.56	21	21
SHH Np/Cholesterol	-0.075	0.14	-10000	0	-0.32	123	123
PTCH1	-0.047	0.18	-10000	0	-0.6	26	26
HHIP	-0.14	0.25	-10000	0	-0.55	142	142

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.15	0.38	-9999	-1	68	68
MKNK1	0.009	0.053	-9999	-0.59	4	4
MAPK14	-0.037	0.12	-9999	-0.28	80	80
ATF2/c-Jun	-0.028	0.14	-9999	-0.57	17	17
MAPK11	-0.049	0.15	-9999	-0.55	16	16
MITF	-0.041	0.16	-9999	-0.35	90	90
MAPKAPK5	-0.039	0.16	-9999	-0.34	88	88
KRT8	-0.11	0.22	-9999	-0.42	132	132
MAPKAPK3	0.012	0.038	-9999	-0.59	2	2
MAPKAPK2	0.014	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.062	0.19	-9999	-0.44	88	88
CEBPB	-0.052	0.18	-9999	-0.39	96	96
SLC9A1	-0.04	0.16	-9999	-0.35	88	88
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.044	0.17	-9999	-0.35	97	97
p38alpha-beta/MNK1	-0.038	0.16	-9999	-0.35	89	89
JUN	-0.027	0.14	-9999	-0.57	17	17
PPARGC1A	-0.056	0.18	-9999	-0.39	97	97
USF1	-0.039	0.16	-9999	-0.34	88	88
RAB5/GDP/GDI1	-0.051	0.095	-9999	-0.38	10	10
NOS2	-0.082	0.28	-9999	-1	27	27
DDIT3	-0.044	0.16	-9999	-0.35	89	89
RAB5A	0.014	0	-9999	-10000	0	0
HSPB1	-0.042	0.15	-9999	-0.38	40	40
p38alpha-beta/HBP1	-0.035	0.16	-9999	-0.34	88	88
CREB1	-0.041	0.17	-9999	-0.37	87	87
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	-0.027	0.14	-9999	-0.56	10	10
RPS6KA4	-0.039	0.16	-9999	-0.34	88	88
PLA2G4A	-0.046	0.17	-9999	-0.52	31	31
GDI1	-0.039	0.16	-9999	-0.34	88	88
TP53	-0.06	0.2	-9999	-0.43	95	95
RPS6KA5	-0.047	0.17	-9999	-0.36	95	95
ESR1	-0.054	0.17	-9999	-0.37	101	101
HBP1	0.014	0	-9999	-10000	0	0
MEF2C	-0.049	0.16	-9999	-0.36	96	96
MEF2A	-0.04	0.16	-9999	-0.35	88	88
EIF4EBP1	-0.044	0.17	-9999	-0.37	92	92
KRT19	-0.1	0.22	-9999	-0.41	134	134
ELK4	-0.039	0.16	-9999	-0.34	88	88
ATF6	-0.039	0.16	-9999	-0.34	88	88
ATF1	-0.041	0.17	-9999	-0.36	90	90
p38alpha-beta/MAPKAPK2	-0.035	0.16	-9999	-0.34	88	88
p38alpha-beta/MAPKAPK3	-0.037	0.16	-9999	-0.34	89	89

×

IL4-mediated signaling events

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
BCL2L1	-0.39	0.43	-10000	0	-1.1	81	81
STAT6 (cleaved dimer)	-0.47	0.43	-10000	0	-1	152	152
IGHG1	-0.16	0.21	-10000	0	-0.84	17	17
IGHG3	-0.39	0.41	-10000	0	-0.99	114	114
AKT1	-0.24	0.29	-10000	0	-0.77	65	65
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.22	0.3	-10000	0	-0.8	66	66
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.23	0.26	-10000	0	-0.72	53	53
THY1	-0.41	0.46	-10000	0	-1.2	85	85
MYB	-0.065	0.2	-10000	0	-0.54	73	73
HMGA1	0.01	0.047	-10000	0	-0.52	4	4
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.32	0.34	-10000	0	-0.81	117	117
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.23	0.27	-10000	0	-0.73	52	52
SP1	0.02	0.01	-10000	0	-10000	0	0
INPP5D	0.008	0.06	-10000	0	-0.54	6	6
SOCS5	0.027	0.017	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.45	0.45	-10000	0	-1.1	144	144
SOCS1	-0.3	0.33	-10000	0	-0.8	87	87
SOCS3	-0.35	0.41	-10000	0	-0.96	118	118
FCER2	-0.42	0.44	-10000	0	-1.1	106	106
PARP14	-0.002	0.084	-10000	0	-0.52	13	13
CCL17	-0.4	0.44	-10000	0	-1.1	87	87
GRB2	0.013	0.022	-10000	0	-0.49	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.19	0.23	-10000	0	-0.65	49	49
T cell proliferation	-0.41	0.45	-10000	0	-1.1	104	104
IL4R/JAK1	-0.4	0.43	-10000	0	-1.1	87	87
EGR2	-0.52	0.55	-10000	0	-1.3	131	131
JAK2	-0.004	0.027	-10000	0	-10000	0	0
JAK3	-0.058	0.18	-10000	0	-0.53	68	68
PIK3R1	0.014	0	-10000	0	-10000	0	0
JAK1	0.005	0.012	-10000	0	-10000	0	0
COL1A2	-0.16	0.24	-10000	0	-0.72	46	46
CCL26	-0.4	0.44	-10000	0	-1.1	90	90
IL4R	-0.42	0.46	-10000	0	-1.2	87	87
PTPN6	0.007	0.099	-10000	0	-0.54	16	16
IL13RA2	-0.61	0.58	-10000	0	-1.3	194	194
IL13RA1	-0.015	0.084	-10000	0	-0.61	9	9
IRF4	-0.18	0.33	-10000	0	-1.1	44	44
ARG1	-0.13	0.23	-10000	0	-0.85	28	28
CBL	-0.3	0.32	-10000	0	-0.79	103	103
GTF3A	0.009	0.033	-10000	0	-10000	0	0
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
IL13RA1/JAK2	-0.015	0.07	-10000	0	-0.45	9	9
IRF4/BCL6	-0.15	0.31	-10000	0	-1	44	44
CD40LG	-0.035	0.15	-10000	0	-0.5	46	46
MAPK14	-0.32	0.35	-10000	0	-0.82	121	121
mitosis	-0.23	0.27	-10000	0	-0.72	65	65
STAT6	-0.45	0.5	-10000	0	-1.2	110	110
SPI1	-0.004	0.11	-10000	0	-0.54	19	19
RPS6KB1	-0.21	0.26	-10000	0	-0.7	60	60
STAT6 (dimer)	-0.45	0.5	-10000	0	-1.2	110	110
STAT6 (dimer)/PARP14	-0.43	0.47	-10000	0	-1.1	112	112
mast cell activation	0.011	0.012	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.27	0.32	-10000	0	-0.82	81	81
FRAP1	-0.24	0.29	-10000	0	-0.77	65	65
LTA	-0.43	0.49	-10000	0	-1.2	96	96
FES	0.01	0.047	-10000	0	-0.52	4	4
T-helper 1 cell differentiation	0.44	0.48	1.1	110	-10000	0	110
CCL11	-0.39	0.42	-10000	0	-1.1	78	78
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.25	0.3	-10000	0	-0.82	69	69
IL2RG	-0.041	0.16	-10000	0	-0.52	53	53
IL10	-0.5	0.56	-10000	0	-1.3	124	124
IRS1	0.014	0	-10000	0	-10000	0	0
IRS2	0.012	0.035	-10000	0	-0.54	2	2
IL4	-0.097	0.11	-10000	0	-10000	0	0
IL5	-0.4	0.43	-10000	0	-1.1	82	82
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.33	0.35	-10000	0	-0.85	86	86
COL1A1	-0.35	0.5	-10000	0	-1.2	114	114
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.39	0.44	-10000	0	-1.2	74	74
IL2R gamma/JAK3	-0.073	0.19	-10000	0	-0.44	101	101
TFF3	-0.41	0.45	-10000	0	-1.1	91	91
ALOX15	-0.4	0.44	-10000	0	-1.1	91	91
MYBL1	0.01	0.044	-10000	0	-0.49	4	4
T-helper 2 cell differentiation	-0.36	0.37	-10000	0	-0.89	108	108
SHC1	0.009	0.049	-10000	0	-0.49	5	5
CEBPB	-0.003	0.11	-10000	0	-0.57	17	17
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.22	0.26	-10000	0	-0.69	54	54
mol:PI-3-4-5-P3	-0.24	0.29	-10000	0	-0.77	65	65
PI3K	-0.25	0.31	-10000	0	-0.83	65	65
DOK2	-0.07	0.2	-10000	0	-0.53	80	80
ETS1	0.014	0.08	-10000	0	-0.52	11	11
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.17	0.22	-10000	0	-0.62	47	47
ITGB3	-0.43	0.48	-10000	0	-1.2	93	93
PIGR	-0.5	0.55	-10000	0	-1.3	125	125
IGHE	0.021	0.062	-10000	0	-0.26	9	9
MAPKKK cascade	-0.17	0.22	-10000	0	-0.61	47	47
BCL6	0.016	0.006	-10000	0	-10000	0	0
OPRM1	-0.41	0.44	-10000	0	-1.1	98	98
RETNLB	-0.4	0.43	-10000	0	-1.1	82	82
SELP	-0.41	0.44	-10000	0	-1.1	81	81
AICDA	-0.38	0.42	-10000	0	-1.1	86	86

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.008	0.049	-10000	0	-0.49	5	5
GNB1/GNG2	-0.079	0.08	-10000	0	-0.18	160	160
AKT1	-0.06	0.12	-10000	0	-0.21	93	93
EGF	-0.05	0.18	-10000	0	-0.56	58	58
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.018	0.07	-10000	0	-0.3	5	5
mol:Ca2+	-0.1	0.16	-10000	0	-0.3	156	156
LYN	0.014	0.079	-10000	0	-0.32	11	11
RhoA/GTP	-0.051	0.053	-10000	0	-0.14	17	17
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.12	0.18	-10000	0	-0.35	156	156
GNG2	0.009	0.053	-10000	0	-0.59	4	4
ARRB2	0.014	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.01	0.098	-10000	0	-0.39	24	24
G beta5/gamma2	-0.098	0.1	-10000	0	-0.24	156	156
PRKCH	-0.11	0.18	-10000	0	-0.34	155	155
DNM1	-0.1	0.22	-10000	0	-0.52	112	112
TXA2/TP beta/beta Arrestin3	-0.041	0.072	-10000	0	-0.24	30	30
mol:GTP	-0.001	0.001	-10000	0	-10000	0	0
PTGDR	-0.039	0.16	-10000	0	-0.5	52	52
G12 family/GTP	-0.13	0.13	-10000	0	-0.3	154	154
ADRBK1	0.014	0	-10000	0	-10000	0	0
ADRBK2	0.01	0.051	-10000	0	-0.57	4	4
RhoA/GTP/ROCK1	0.004	0.008	-10000	0	-10000	0	0
mol:GDP	0.057	0.11	0.29	32	-10000	0	32
mol:NADP	0.005	0.071	-10000	0	-0.52	9	9
RAB11A	0.014	0	-10000	0	-10000	0	0
PRKG1	-0.039	0.17	-10000	0	-0.58	46	46
mol:IP3	-0.13	0.19	-10000	0	-0.37	156	156
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	-0.18	0.25	-10000	0	-0.5	156	156
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.038	0.11	-10000	0	-0.33	18	18
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.01	0.088	-10000	0	-0.34	14	14
RHOA	0.014	0	-10000	0	-10000	0	0
PTGIR	-0.015	0.12	-10000	0	-0.52	28	28
PRKCB1	-0.12	0.19	-10000	0	-0.36	155	155
GNAQ	0.014	0	-10000	0	-10000	0	0
mol:L-citrulline	0.005	0.071	-10000	0	-0.52	9	9
TXA2/TXA2-R family	-0.18	0.26	-10000	0	-0.52	161	161
LCK	-0.023	0.12	-10000	0	-0.33	25	25
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.025	0.066	-10000	0	-0.35	6	6
TXA2-R family/G12 family/GDP/G beta/gamma	0.024	0.044	-10000	0	-0.75	1	1
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.023	0.063	-10000	0	-0.38	4	4
MAPK14	-0.071	0.13	-10000	0	-0.23	149	149
TGM2/GTP	-0.14	0.21	-10000	0	-0.42	158	158
MAPK11	-0.074	0.13	-10000	0	-0.24	150	150
ARHGEF1	-0.053	0.097	-10000	0	-0.18	96	96
GNAI2	0.014	0	-10000	0	-10000	0	0
JNK cascade	-0.13	0.2	-10000	0	-0.38	163	163
RAB11/GDP	0.015	0.001	-10000	0	-10000	0	0
ICAM1	-0.099	0.16	-10000	0	-0.29	162	162
cAMP biosynthetic process	-0.12	0.18	-10000	0	-0.35	159	159
Gq family/GTP/EBP50	0.007	0.083	-10000	0	-0.29	27	27
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0.019	0.068	-10000	0	-0.3	5	5
GNB5	0.014	0	-10000	0	-10000	0	0
GNB1	0.014	0	-10000	0	-10000	0	0
EGF/EGFR	-0.024	0.11	-10000	0	-0.3	27	27
VCAM1	-0.13	0.19	-10000	0	-0.37	160	160
TP beta/Gq family/GDP/G beta5/gamma2	0.01	0.098	-10000	0	-0.39	24	24
platelet activation	-0.094	0.17	-10000	0	-0.3	154	154
PGI2/IP	-0.016	0.087	-10000	0	-0.38	28	28
PRKACA	-0.01	0.08	-10000	0	-0.29	18	18
Gq family/GDP/G beta5/gamma2	0.009	0.093	-10000	0	-0.36	24	24
TXA2/TP beta/beta Arrestin2	-0.062	0.14	-10000	0	-0.53	35	35
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.005	0.085	-10000	0	-0.29	25	25
mol:DAG	-0.14	0.21	-10000	0	-0.41	156	156
EGFR	-0.083	0.21	-10000	0	-0.55	89	89
TXA2/TP alpha	-0.17	0.24	-10000	0	-0.48	159	159
Gq family/GTP	-0.015	0.068	-10000	0	-0.24	38	38
YES1	0.017	0.072	-10000	0	-0.31	4	4
GNAI2/GTP	-0.023	0.061	-10000	0	-0.35	5	5
PGD2/DP	-0.033	0.11	-10000	0	-0.36	52	52
SLC9A3R1	0.009	0.053	-10000	0	-0.59	4	4
FYN	0.019	0.068	-10000	0	-0.3	5	5
mol:NO	0.005	0.071	-10000	0	-0.52	9	9
GNA15	-0.007	0.11	-10000	0	-0.57	19	19
PGK/cGMP	-0.037	0.11	-10000	0	-0.36	54	54
RhoA/GDP	0.015	0.001	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.023	0.074	-10000	0	-0.42	6	6
NOS3	0.005	0.071	-10000	0	-0.52	9	9
RAC1	0.014	0	-10000	0	-10000	0	0
PRKCA	-0.11	0.18	-10000	0	-0.34	151	151
PRKCB	-0.14	0.2	-10000	0	-0.38	169	169
PRKCE	-0.11	0.18	-10000	0	-0.35	147	147
PRKCD	-0.13	0.2	-10000	0	-0.39	157	157
PRKCG	-0.17	0.22	-10000	0	-0.42	190	190
muscle contraction	-0.17	0.25	-10000	0	-0.48	164	164
PRKCZ	-0.12	0.19	-10000	0	-0.35	166	166
ARR3	0.002	0.022	-10000	0	-0.49	1	1
TXA2/TP beta	-0.025	0.069	-10000	0	-0.36	7	7
PRKCQ	-0.12	0.18	-10000	0	-0.35	161	161
MAPKKK cascade	-0.16	0.23	-10000	0	-0.45	160	160
SELE	-0.12	0.18	-10000	0	-0.33	177	177
TP beta/GNAI2/GDP/G beta/gamma	-0.021	0.067	-10000	0	-0.37	5	5
ROCK1	0.014	0	-10000	0	-10000	0	0
GNA14	-0.014	0.12	-10000	0	-0.56	25	25
chemotaxis	-0.21	0.3	-10000	0	-0.6	159	159
GNA12	0.013	0.027	-10000	0	-0.59	1	1
GNA13	0.014	0	-10000	0	-10000	0	0
GNA11	0.004	0.079	-10000	0	-0.59	9	9
Rac1/GTP	0.004	0.005	-10000	0	-10000	0	0

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0	0.055	-9999	-10000	0	0
Syndecan-4/Syndesmos	-0.13	0.24	-9999	-0.56	100	100
positive regulation of JNK cascade	-0.14	0.22	-9999	-0.52	108	108
Syndecan-4/ADAM12	-0.17	0.26	-9999	-0.57	119	119
CCL5	-0.086	0.21	-9999	-0.53	94	94
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0.014	0	-9999	-10000	0	0
ITGA5	-0.01	0.11	-9999	-0.5	24	24
SDCBP	0.014	0	-9999	-10000	0	0
PLG	0.001	0.043	-9999	-0.48	4	4
ADAM12	-0.07	0.19	-9999	-0.5	84	84
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.014	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.03	0.043	-9999	-0.18	1	1
Syndecan-4/Laminin alpha1	-0.16	0.27	-9999	-0.59	116	116
Syndecan-4/CXCL12/CXCR4	-0.13	0.25	-9999	-0.55	108	108
Syndecan-4/Laminin alpha3	-0.15	0.26	-9999	-0.58	112	112
MDK	-0.042	0.17	-9999	-0.54	52	52
Syndecan-4/FZD7	-0.16	0.28	-9999	-0.61	112	112
Syndecan-4/Midkine	-0.16	0.26	-9999	-0.58	107	107
FZD7	-0.048	0.18	-9999	-0.58	54	54
Syndecan-4/FGFR1/FGF	-0.14	0.2	-9999	-0.51	102	102
THBS1	-0.09	0.21	-9999	-0.51	102	102
integrin-mediated signaling pathway	-0.15	0.26	-9999	-0.57	111	111
positive regulation of MAPKKK cascade	-0.14	0.22	-9999	-0.52	108	108
Syndecan-4/TACI	-0.14	0.24	-9999	-0.56	101	101
CXCR4	-0.013	0.12	-9999	-0.54	25	25
cell adhesion	0.021	0.052	-9999	-0.26	11	11
Syndecan-4/Dynamin	-0.13	0.24	-9999	-0.56	100	100
Syndecan-4/TSP1	-0.18	0.26	-9999	-0.58	120	120
Syndecan-4/GIPC	-0.13	0.24	-9999	-0.56	100	100
Syndecan-4/RANTES	-0.18	0.26	-9999	-0.59	113	113
ITGB1	0.012	0.031	-9999	-0.49	2	2
LAMA1	-0.063	0.2	-9999	-0.57	68	68
LAMA3	-0.041	0.17	-9999	-0.54	51	51
RAC1	0.014	0	-9999	-10000	0	0
PRKCA	0.037	0.053	-9999	-0.53	1	1
Syndecan-4/alpha-Actinin	-0.14	0.25	-9999	-0.57	112	112
TFPI	-0.091	0.21	-9999	-0.52	101	101
F2	-0.008	0.069	-9999	-0.49	10	10
alpha5/beta1 Integrin	-0.017	0.079	-9999	-0.36	25	25
positive regulation of cell adhesion	-0.18	0.28	-9999	-0.6	125	125
ACTN1	-0.021	0.13	-9999	-0.5	36	36
TNC	-0.049	0.18	-9999	-0.54	59	59
Syndecan-4/CXCL12	-0.13	0.24	-9999	-0.56	103	103
FGF6	0.001	0.003	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
CXCL12	0.003	0.077	-9999	-0.54	10	10
TNFRSF13B	-0.005	0.072	-9999	-0.49	11	11
FGF2	0.011	0.044	-9999	-0.56	3	3
FGFR1	0.013	0.027	-9999	-0.59	1	1
Syndecan-4/PI-4-5-P2	-0.14	0.24	-9999	-0.56	100	100
mol:GDP	0	0	-9999	-10000	0	0
FN1	0	0.092	-9999	-0.48	18	18
cell migration	-0.007	0.018	-9999	-10000	0	0
PRKCD	-0.013	0.13	-9999	-0.57	27	27
vasculogenesis	-0.17	0.25	-9999	-0.56	120	120
SDC4	-0.14	0.25	-9999	-0.6	100	100
Syndecan-4/Tenascin C	-0.16	0.27	-9999	-0.6	111	111
Syndecan-4/PI-4-5-P2/PKC alpha	-0.024	0.034	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.13	0.24	-9999	-0.56	100	100
MMP9	-0.14	0.24	-9999	-0.52	144	144
Rac1/GTP	0.021	0.053	-9999	-0.26	11	11
cytoskeleton organization	-0.12	0.23	-9999	-0.53	100	100
GIPC1	0.013	0.022	-9999	-0.49	1	1
Syndecan-4/TFPI	-0.18	0.26	-9999	-0.6	109	109

×

Glypican 2 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.042	0.17	-9999	-0.54	52	52
GPC2	-0.015	0.13	-9999	-0.57	26	26
GPC2/Midkine	-0.059	0.15	-9999	-0.42	73	73
neuron projection morphogenesis	-0.059	0.15	-9999	-0.42	73	73

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.038	0.05	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.092	0.14	-9999	-0.42	49	49
JUN	-0.08	0.2	-9999	-0.52	59	59
HRAS	0.014	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.16	0.22	-9999	-0.44	145	145
RAP1A	0.014	0	-9999	-10000	0	0
FRS2	0.012	0.035	-9999	-0.54	2	2
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.16	0.22	-9999	-0.44	144	144
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.014	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.014	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.095	0.17	-9999	-0.4	95	95
RHOA	0.014	0	-9999	-10000	0	0
RAP1A/GTP	-0.14	0.2	-9999	-0.54	71	71
GRB7	-0.032	0.14	-9999	-0.49	43	43
RET51/GFRalpha1/GDNF	-0.15	0.22	-9999	-0.43	144	144
MAPKKK cascade	-0.12	0.18	-9999	-0.56	51	51
BCAR1	0.013	0.027	-9999	-0.59	1	1
RET9/GFRalpha1/GDNF/IRS1	-0.09	0.17	-9999	-0.36	131	131
lamellipodium assembly	-0.086	0.13	-9999	-0.39	50	50
RET51/GFRalpha1/GDNF/SHC	-0.16	0.22	-9999	-0.44	144	144
PIK3CA	0.013	0.027	-9999	-0.59	1	1
RET9/GFRalpha1/GDNF/SHC	-0.093	0.17	-9999	-0.4	95	95
RET9/GFRalpha1/GDNF/Shank3	-0.095	0.17	-9999	-0.36	138	138
MAPK3	-0.11	0.21	-9999	-0.57	55	55
DOK1	0.012	0.035	-9999	-0.54	2	2
DOK6	-0.05	0.18	-9999	-0.58	56	56
PXN	0.014	0	-9999	-10000	0	0
neurite development	-0.1	0.22	-9999	-0.53	72	72
DOK5	0.001	0.088	-9999	-0.59	11	11
GFRA1	-0.071	0.2	-9999	-0.56	77	77
MAPK8	-0.087	0.2	-9999	-0.57	52	52
HRAS/GTP	-0.14	0.2	-9999	-0.56	66	66
tube development	-0.088	0.16	-9999	-0.37	97	97
MAPK1	-0.11	0.21	-9999	-0.57	55	55
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.042	0.15	-9999	-0.32	95	95
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.014	0	-9999	-10000	0	0
PDLIM7	0.005	0.066	-9999	-0.49	9	9
RET51/GFRalpha1/GDNF/Dok6	-0.17	0.26	-9999	-0.66	79	79
SHC1	0.009	0.049	-9999	-0.49	5	5
RET51/GFRalpha1/GDNF/Dok4	-0.16	0.23	-9999	-0.45	151	151
RET51/GFRalpha1/GDNF/Dok5	-0.16	0.22	-9999	-0.44	152	152
PRKCA	0.013	0.027	-9999	-0.59	1	1
HRAS/GDP	0	0	-9999	-10000	0	0
CREB1	-0.069	0.18	-9999	-0.48	57	57
PIK3R1	0.014	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.044	0.15	-9999	-0.32	95	95
RET51/GFRalpha1/GDNF/Grb7	-0.18	0.24	-9999	-0.47	147	147
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.11	0.24	-9999	-0.55	117	117
DOK4	-0.005	0.1	-9999	-0.59	16	16
JNK cascade	-0.078	0.19	-9999	-0.51	59	59
RET9/GFRalpha1/GDNF/FRS2	-0.091	0.17	-9999	-0.36	132	132
SHANK3	0.004	0.073	-9999	-0.51	10	10
RASA1	0.014	0	-9999	-10000	0	0
NCK1	0.013	0.027	-9999	-0.59	1	1
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.043	0.15	-9999	-0.32	95	95
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.092	0.2	-9999	-0.5	64	64
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.092	0.2	-9999	-0.49	66	66
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.096	0.21	-9999	-0.52	65	65
PI3K	-0.09	0.23	-9999	-0.59	58	58
SOS1	0.014	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.088	0.16	-9999	-0.37	97	97
GRB10	0.011	0.044	-9999	-0.56	3	3
activation of MAPKK activity	-0.087	0.2	-9999	-0.46	83	83
RET51/GFRalpha1/GDNF/FRS2	-0.16	0.22	-9999	-0.44	144	144
GAB1	0.012	0.035	-9999	-0.54	2	2
IRS1	0.014	0	-9999	-10000	0	0
IRS2	0.012	0.035	-9999	-0.54	2	2
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.097	0.21	-9999	-0.62	48	48
RET51/GFRalpha1/GDNF/PKC alpha	-0.15	0.22	-9999	-0.44	144	144
GRB2	0.013	0.022	-9999	-0.49	1	1
PRKACA	0.014	0	-9999	-10000	0	0
GDNF	-0.071	0.21	-9999	-0.57	74	74
RAC1	0.014	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.15	0.22	-9999	-0.43	144	144
Rac1/GTP	-0.1	0.15	-9999	-0.47	50	50
RET9/GFRalpha1/GDNF	-0.1	0.18	-9999	-0.4	131	131
GFRalpha1/GDNF	-0.12	0.21	-9999	-0.46	131	131

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.013	0.027	-9999	-0.59	1	1
Aurora C/Aurora B/INCENP	-0.11	0.16	-9999	-0.31	178	178
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.031	0.045	-9999	-0.25	1	1
AURKB	-0.16	0.26	-9999	-0.55	157	157
AURKC	-0.021	0.13	-9999	-0.52	34	34

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	-0.026	0.1	-9999	-0.43	31	31
VLDLR	-0.007	0.11	-9999	-0.57	19	19
CRKL	0.013	0.022	-9999	-0.49	1	1
LRPAP1	0.014	0	-9999	-10000	0	0
FYN	0.014	0	-9999	-10000	0	0
ITGA3	-0.009	0.11	-9999	-0.5	23	23
RELN/VLDLR/Fyn	-0.1	0.16	-9999	-0.34	153	153
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.011	0.055	-9999	-10000	0	0
AKT1	-0.072	0.16	-9999	-0.49	31	31
MAP2K7	0.014	0	-9999	-10000	0	0
RAPGEF1	0.014	0	-9999	-10000	0	0
DAB1	-0.089	0.22	-9999	-0.56	92	92
RELN/LRP8/DAB1	-0.14	0.18	-9999	-0.39	140	140
LRPAP1/LRP8	-0.002	0.027	-9999	-0.43	2	2
RELN/LRP8/DAB1/Fyn	-0.12	0.17	-9999	-0.36	139	139
DAB1/alpha3/beta1 Integrin	-0.13	0.18	-9999	-0.54	51	51
long-term memory	-0.28	0.28	-9999	-0.64	164	164
DAB1/LIS1	-0.12	0.17	-9999	-0.54	39	39
DAB1/CRLK/C3G	-0.12	0.16	-9999	-0.53	39	39
PIK3CA	0.013	0.027	-9999	-0.59	1	1
DAB1/NCK2	-0.12	0.17	-9999	-0.55	39	39
ARHGEF2	0.013	0.027	-9999	-0.59	1	1
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.16	0.26	-9999	-0.55	158	158
CDK5R1	-0.022	0.14	-9999	-0.59	31	31
RELN	-0.14	0.25	-9999	-0.55	140	140
PIK3R1	0.014	0	-9999	-10000	0	0
RELN/LRP8/Fyn	-0.089	0.15	-9999	-0.32	141	141
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.2	0.23	-9999	-0.59	106	106
MAPK8	-0.002	0.099	-9999	-0.59	14	14
RELN/VLDLR/DAB1	-0.14	0.19	-9999	-0.35	212	212
ITGB1	0.012	0.031	-9999	-0.49	2	2
MAP1B	-0.11	0.2	-9999	-0.37	141	141
RELN/LRP8	-0.089	0.15	-9999	-0.32	141	141
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.22	0.23	-9999	-0.59	106	106
PI3K	-0.001	0.019	-9999	-0.43	1	1
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.017	0.078	-9999	-0.36	24	24
RAP1A	-0.072	0.18	-9999	-0.49	39	39
PAFAH1B1	0.014	0	-9999	-10000	0	0
MAPK8IP1	0.009	0.053	-9999	-0.59	4	4
CRLK/C3G	-0.001	0.015	-9999	-0.34	1	1
GRIN2B	-0.18	0.26	-9999	-0.54	180	180
NCK2	0.014	0	-9999	-10000	0	0
neuron differentiation	-0.043	0.14	-9999	-0.42	34	34
neuron adhesion	-0.065	0.18	-9999	-0.47	51	51
LRP8	0.012	0.038	-9999	-0.59	2	2
GSK3B	-0.061	0.15	-9999	-0.47	30	30
RELN/VLDLR/DAB1/Fyn	-0.13	0.18	-9999	-0.37	148	148
MAP3K11	0.014	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.085	0.17	-9999	-0.31	148	148
CDK5	0.014	0	-9999	-10000	0	0
MAPT	0.011	0.082	-9999	-0.54	10	10
neuron migration	-0.07	0.19	-9999	-0.51	43	43
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.043	0.14	-9999	-0.42	34	34
RELN/VLDLR	-0.09	0.14	-9999	-0.34	93	93

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.012	0.031	-9999	-0.49	2	2
ITGB7	-0.034	0.16	-9999	-0.54	45	45
ITGA4	-0.052	0.18	-9999	-0.53	62	62
alpha4/beta7 Integrin	-0.077	0.17	-9999	-0.43	93	93
alpha4/beta1 Integrin	-0.047	0.13	-9999	-0.39	62	62

×

Endothelins

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
AKT1	-0.092	0.21	-10000	0	-0.57	49	49
PTK2B	-0.009	0.11	-10000	0	-0.49	24	24
mol:Ca2+	-0.062	0.24	-10000	0	-0.71	43	43
EDN1	-0.08	0.18	-10000	0	-0.53	51	51
EDN3	-0.017	0.13	-10000	0	-0.58	27	27
EDN2	-0.017	0.1	-10000	0	-0.49	23	23
HRAS/GDP	-0.093	0.21	-10000	0	-0.52	61	61
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.051	0.16	-10000	0	-0.43	43	43
ADCY4	-0.11	0.23	-10000	0	-0.52	90	90
ADCY5	-0.12	0.24	-10000	0	-0.56	89	89
ADCY6	-0.1	0.22	-10000	0	-0.51	86	86
ADCY7	-0.1	0.22	-10000	0	-0.51	86	86
ADCY1	-0.16	0.25	-10000	0	-0.54	118	118
ADCY2	-0.11	0.23	-10000	0	-0.53	92	92
ADCY3	-0.1	0.22	-10000	0	-0.51	86	86
ADCY8	-0.14	0.25	-10000	0	-0.54	113	113
ADCY9	-0.11	0.22	-10000	0	-0.51	88	88
arachidonic acid secretion	-0.095	0.22	-10000	0	-0.52	74	74
ETB receptor/Endothelin-1/Gq/GTP	-0.045	0.16	-10000	0	-0.41	52	52
GNAO1	0.008	0.059	-10000	0	-0.59	5	5
HRAS	0.013	0.004	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	-0.094	0.2	0.26	19	-0.54	48	67
ETA receptor/Endothelin-1/Gs/GTP	-0.13	0.23	0.24	18	-0.54	86	104
mol:GTP	0	0.005	-10000	0	-10000	0	0
COL3A1	-0.19	0.32	-10000	0	-0.62	155	155
EDNRB	-0.045	0.18	-10000	0	-0.59	49	49
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.11	0.26	-10000	0	-0.68	59	59
CYSLTR1	-0.1	0.24	-10000	0	-0.65	55	55
SLC9A1	-0.066	0.099	-10000	0	-0.31	32	32
mol:GDP	-0.11	0.22	-10000	0	-0.53	71	71
SLC9A3	-0.095	0.27	-10000	0	-0.69	67	67
RAF1	-0.11	0.23	-10000	0	-0.52	78	78
JUN	-0.045	0.2	-10000	0	-0.6	32	32
JAK2	-0.092	0.21	-10000	0	-0.57	49	49
mol:IP3	-0.058	0.18	-10000	0	-0.5	43	43
ETA receptor/Endothelin-1	-0.13	0.24	0.3	19	-0.61	58	77
PLCB1	-0.01	0.11	-10000	0	-0.59	19	19
PLCB2	-0.009	0.11	-10000	0	-0.57	19	19
ETA receptor/Endothelin-3	-0.072	0.16	-10000	0	-0.47	57	57
FOS	-0.15	0.33	-10000	0	-0.85	78	78
Gai/GDP	0.006	0.11	-10000	0	-0.97	5	5
CRK	0.014	0.001	-10000	0	-10000	0	0
mol:Ca ++	-0.12	0.25	-10000	0	-0.56	86	86
BCAR1	0.013	0.027	-10000	0	-0.59	1	1
PRKCB1	-0.057	0.17	-10000	0	-0.47	44	44
GNAQ	0.013	0.007	-10000	0	-10000	0	0
GNAZ	0.014	0	-10000	0	-10000	0	0
GNAL	-0.058	0.2	-10000	0	-0.59	62	62
Gs family/GDP	-0.15	0.21	-10000	0	-0.51	101	101
ETA receptor/Endothelin-1/Gq/GTP	-0.05	0.15	-10000	0	-0.4	47	47
MAPK14	-0.037	0.16	-10000	0	-0.53	28	28
TRPC6	-0.066	0.25	-10000	0	-0.75	43	43
GNAI2	0.014	0	-10000	0	-10000	0	0
GNAI3	0.014	0	-10000	0	-10000	0	0
GNAI1	-0.005	0.1	-10000	0	-0.59	16	16
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.047	0.17	-10000	0	-0.46	44	44
ETB receptor/Endothelin-2	-0.047	0.15	-10000	0	-0.41	71	71
ETB receptor/Endothelin-3	-0.047	0.17	-10000	0	-0.46	69	69
ETB receptor/Endothelin-1	-0.096	0.19	-10000	0	-0.46	88	88
MAPK3	-0.14	0.3	-10000	0	-0.74	82	82
MAPK1	-0.14	0.3	-10000	0	-0.74	82	82
Rac1/GDP	-0.092	0.21	-10000	0	-0.52	60	60
cAMP biosynthetic process	-0.12	0.24	-10000	0	-0.54	97	97
MAPK8	-0.06	0.22	-10000	0	-0.62	46	46
SRC	0.014	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.02	0.12	-10000	0	-0.36	31	31
p130Cas/CRK/Src/PYK2	-0.097	0.23	-10000	0	-0.55	66	66
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.092	0.21	-10000	0	-0.52	60	60
COL1A2	-0.13	0.28	-10000	0	-0.68	80	80
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.069	0.14	-10000	0	-0.42	54	54
mol:DAG	-0.058	0.18	-10000	0	-0.5	43	43
MAP2K2	-0.12	0.25	-10000	0	-0.59	83	83
MAP2K1	-0.12	0.26	-10000	0	-0.6	84	84
EDNRA	-0.066	0.17	-10000	0	-0.48	51	51
positive regulation of muscle contraction	-0.071	0.19	-10000	0	-0.5	48	48
Gq family/GDP	-0.12	0.2	-10000	0	-0.55	60	60
HRAS/GTP	-0.1	0.21	-10000	0	-0.5	74	74
PRKCH	-0.049	0.17	-10000	0	-0.49	38	38
RAC1	0.014	0	-10000	0	-10000	0	0
PRKCA	-0.05	0.18	-10000	0	-0.5	38	38
PRKCB	-0.087	0.2	-10000	0	-0.49	64	64
PRKCE	-0.054	0.18	-10000	0	-0.5	40	40
PRKCD	-0.065	0.2	-10000	0	-0.58	44	44
PRKCG	-0.15	0.23	-10000	0	-0.48	119	119
regulation of vascular smooth muscle contraction	-0.17	0.38	-10000	0	-1	73	73
PRKCQ	-0.058	0.19	-10000	0	-0.51	48	48
PLA2G4A	-0.1	0.24	-10000	0	-0.56	75	75
GNA14	-0.014	0.12	-10000	0	-0.56	25	25
GNA15	-0.008	0.11	-10000	0	-0.57	19	19
GNA12	0.013	0.027	-10000	0	-0.59	1	1
GNA11	0.003	0.08	-10000	0	-0.59	9	9
Rac1/GTP	-0.093	0.2	0.26	19	-0.53	48	67
MMP1	0.013	0.16	-10000	0	-0.43	33	33

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.077	0.17	-9999	-0.47	69	69
alphaM/beta2 Integrin/GPIbA	-0.073	0.16	-9999	-0.46	68	68
alphaM/beta2 Integrin/proMMP-9	-0.15	0.21	-9999	-0.4	180	180
PLAUR	-0.02	0.13	-9999	-0.5	35	35
HMGB1	-0.001	0.022	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.062	0.16	-9999	-0.49	52	52
AGER	-0.029	0.13	-9999	-0.6	24	24
RAP1A	0.014	0	-9999	-10000	0	0
SELPLG	-0.023	0.14	-9999	-0.58	32	32
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.13	0.18	-9999	-0.54	60	60
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.14	0.24	-9999	-0.52	144	144
CYR61	-0.099	0.23	-9999	-0.55	104	104
TLN1	0.014	0	-9999	-10000	0	0
Rap1/GTP	-0.088	0.13	-9999	-0.42	42	42
RHOA	0.014	0	-9999	-10000	0	0
P-selectin oligomer	-0.027	0.13	-9999	-0.49	38	38
MYH2	-0.085	0.15	-9999	-0.41	53	53
MST1R	0.006	0.069	-9999	-0.58	7	7
leukocyte activation during inflammatory response	-0.11	0.18	-9999	-0.41	103	103
APOB	-0.074	0.2	-9999	-0.55	80	80
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.012	0.12	-9999	-0.54	25	25
JAM3	0.014	0	-9999	-10000	0	0
GP1BA	-0.004	0.1	-9999	-0.57	16	16
alphaM/beta2 Integrin/CTGF	-0.086	0.18	-9999	-0.47	77	77
alphaM/beta2 Integrin	-0.096	0.16	-9999	-0.42	70	70
JAM3 homodimer	0.014	0	-9999	-10000	0	0
ICAM2	0.013	0.022	-9999	-0.49	1	1
ICAM1	-0.026	0.14	-9999	-0.51	40	40
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.095	0.16	-9999	-0.41	70	70
cell adhesion	-0.073	0.16	-9999	-0.46	68	68
NFKB1	-0.16	0.26	-9999	-0.63	80	80
THY1	-0.004	0.1	-9999	-0.56	16	16
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.07	0.14	-9999	-0.33	109	109
alphaM/beta2 Integrin/LRP/tPA	-0.082	0.17	-9999	-0.47	61	61
IL6	-0.21	0.33	-9999	-0.77	98	98
ITGB2	-0.044	0.15	-9999	-0.57	38	38
elevation of cytosolic calcium ion concentration	-0.11	0.2	-9999	-0.51	79	79
alphaM/beta2 Integrin/JAM2/JAM3	-0.051	0.14	-9999	-0.46	48	48
JAM2	0.013	0.027	-9999	-0.59	1	1
alphaM/beta2 Integrin/ICAM1	-0.087	0.18	-9999	-0.5	51	51
alphaM/beta2 Integrin/uPA/Plg	-0.096	0.18	-9999	-0.43	92	92
RhoA/GTP	-0.088	0.16	-9999	-0.42	56	56
positive regulation of phagocytosis	-0.1	0.18	-9999	-0.58	46	46
Ron/MSP	-0.034	0.11	-9999	-0.41	42	42
alphaM/beta2 Integrin/uPAR/uPA	-0.11	0.2	-9999	-0.51	79	79
alphaM/beta2 Integrin/uPAR	-0.082	0.18	-9999	-0.47	77	77
PLAU	-0.059	0.18	-9999	-0.51	73	73
PLAT	-0.049	0.17	-9999	-0.49	64	64
actin filament polymerization	-0.082	0.15	-9999	-0.39	53	53
MST1	-0.026	0.15	-9999	-0.57	35	35
alphaM/beta2 Integrin/lipoprotein(a)	-0.11	0.18	-9999	-0.42	103	103
TNF	-0.23	0.36	-9999	-0.79	115	115
RAP1B	0.013	0.022	-9999	-0.49	1	1
alphaM/beta2 Integrin/uPA	-0.1	0.19	-9999	-0.46	96	96
fibrinolysis	-0.095	0.18	-9999	-0.43	92	92
HCK	-0.007	0.11	-9999	-0.54	20	20
dendritic cell antigen processing and presentation	-0.095	0.16	-9999	-0.41	70	70
VTN	-0.008	0.11	-9999	-0.56	20	20
alphaM/beta2 Integrin/CYR61	-0.13	0.22	-9999	-0.46	128	128
LPA	-0.021	0.12	-9999	-0.49	32	32
LRP1	0.014	0	-9999	-10000	0	0
cell migration	-0.13	0.22	-9999	-0.45	122	122
FN1	-0.003	0.092	-9999	-0.49	18	18
alphaM/beta2 Integrin/Thy1	-0.073	0.17	-9999	-0.48	64	64
MPO	-0.12	0.24	-9999	-0.54	127	127
KNG1	-0.019	0.1	-9999	-0.49	24	24
RAP1/GDP	-0.001	0.013	-9999	-0.29	1	1
ROCK1	-0.076	0.15	-9999	-0.4	51	51
ELA2	0	0	-9999	-10000	0	0
PLG	-0.002	0.043	-9999	-0.49	4	4
CTGF	-0.027	0.15	-9999	-0.54	39	39
alphaM/beta2 Integrin/Hck	-0.073	0.19	-9999	-0.57	56	56
ITGAM	-0.044	0.16	-9999	-0.6	36	36
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.09	0.21	-9999	-0.57	63	63
HP	-0.11	0.23	-9999	-0.53	116	116
leukocyte adhesion	-0.11	0.17	-9999	-0.54	51	51
SELP	-0.027	0.13	-9999	-0.49	38	38

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	-0.041	0.11	-9999	-0.3	71	71
RGS9BP	0.002	0.085	-9999	-0.57	11	11
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0.012	0.022	-9999	-0.49	1	1
mol:Na +	-0.1	0.15	-9999	-0.32	162	162
mol:ADP	0.017	0.042	-9999	-0.34	7	7
GNAT2	0.01	0.032	-9999	-0.49	2	2
RGS9-1/Gbeta5/R9AP	-0.038	0.12	-9999	-0.37	53	53
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.014	0.064	-9999	-0.3	24	24
GRK7	0.006	0.054	-9999	-0.49	6	6
CNGB3	-0.01	0.094	-9999	-0.49	19	19
Cone Metarhodopsin II/X-Arrestin	-0.001	0.015	-9999	-0.35	1	1
mol:Ca2+	-0.14	0.2	-9999	-0.34	234	234
Cone PDE6	-0.044	0.11	-9999	-0.34	47	47
Cone Metarhodopsin II	-0.004	0.03	-9999	-0.26	7	7
Na + (4 Units)	-0.15	0.19	-9999	-0.34	234	234
GNAT2/GDP	-0.033	0.1	-9999	-0.33	47	47
GNB5	0.014	0	-9999	-10000	0	0
mol:GMP (4 units)	0.002	0.067	-9999	-0.26	29	29
Cone Transducin	-0.044	0.11	-9999	-0.32	71	71
SLC24A2	-0.11	0.24	-9999	-0.55	115	115
GNB3/GNGT2	-0.056	0.14	-9999	-0.42	70	70
GNB3	-0.035	0.16	-9999	-0.58	43	43
GNAT2/GTP	-0.001	0.022	-9999	-0.35	2	2
CNGA3	-0.14	0.24	-9999	-0.53	144	144
ARR3	0.002	0.022	-9999	-0.49	1	1
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.1	0.15	-9999	-0.32	162	162
mol:Pi	-0.038	0.12	-9999	-0.37	53	53
Cone CNG Channel	-0.091	0.14	-9999	-0.35	58	58
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.11	0.24	-9999	-0.55	115	115
RGS9	-0.039	0.17	-9999	-0.58	46	46
PDE6C	0.002	0.049	-9999	-0.49	5	5
GNGT2	-0.018	0.13	-9999	-0.55	29	29
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	-0.013	0.1	-9999	-0.49	23	23

×

Caspase cascade in apoptosis

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
TOP1	-0.044	0.15	0.2	2	-0.32	96	98
ACTA1	-0.065	0.18	0.23	2	-0.39	102	104
NUMA1	-0.044	0.15	0.21	1	-0.32	96	97
SPTAN1	-0.055	0.18	0.25	3	-0.39	92	95
LIMK1	-0.055	0.18	0.25	3	-0.39	92	95
BIRC3	-0.033	0.16	-10000	0	-0.55	43	43
BIRC2	0.014	0	-10000	0	-10000	0	0
BAX	0.014	0	-10000	0	-10000	0	0
CASP10	-0.083	0.2	-10000	0	-0.39	140	140
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.014	0	-10000	0	-10000	0	0
PTK2	-0.044	0.15	0.21	1	-0.32	96	97
DIABLO	0.014	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.054	0.18	0.25	3	-0.38	92	95
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.014	0	-10000	0	-10000	0	0
GSN	-0.063	0.18	0.25	1	-0.39	98	99
MADD	0.014	0	-10000	0	-10000	0	0
TFAP2A	-0.19	0.3	-10000	0	-0.65	138	138
BID	-0.039	0.11	-10000	0	-0.24	103	103
MAP3K1	-0.014	0.068	-10000	0	-0.21	7	7
TRADD	0.013	0.027	-10000	0	-0.59	1	1
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.007	0.019	-10000	0	-0.34	1	1
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.057	0.18	0.25	3	-0.39	93	96
CASP9	0.013	0.022	-10000	0	-0.49	1	1
DNA repair	0.003	0.061	0.16	5	-0.19	19	24
neuron apoptosis	0.006	0.045	-10000	0	-0.42	1	1
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.047	0.17	0.24	1	-0.37	91	92
APAF1	0.014	0	-10000	0	-10000	0	0
CASP6	-0.028	0.12	-10000	0	-0.73	4	4
TRAF2	0.014	0	-10000	0	-10000	0	0
ICAD/CAD	-0.046	0.17	0.24	3	-0.37	91	94
CASP7	0.019	0.076	0.27	38	-10000	0	38
KRT18	-0.09	0.21	-10000	0	-0.61	67	67
apoptosis	-0.069	0.18	0.26	1	-0.38	96	97
DFFA	-0.055	0.18	0.25	3	-0.39	92	95
DFFB	-0.055	0.18	0.25	3	-0.39	92	95
PARP1	-0.003	0.061	0.19	19	-0.16	5	24
actin filament polymerization	0.043	0.17	0.36	89	-0.24	3	92
TNF	-0.15	0.26	-10000	0	-0.54	156	156
CYCS	-0.023	0.08	-10000	0	-0.21	39	39
SATB1	-0.024	0.12	-10000	0	-0.53	9	9
SLK	-0.056	0.18	0.25	3	-0.39	93	96
p15 BID/BAX	-0.027	0.099	-10000	0	-0.32	17	17
CASP2	-0.018	0.11	-10000	0	-0.42	12	12
JNK cascade	0.014	0.068	0.21	7	-10000	0	7
CASP3	-0.066	0.19	0.24	5	-0.41	95	100
LMNB2	-0.013	0.093	-10000	0	-0.4	9	9
RIPK1	0.014	0	-10000	0	-10000	0	0
CASP4	-0.013	0.11	-10000	0	-0.5	27	27
Mammalian IAPs/DIABLO	-0.024	0.08	-10000	0	-0.32	25	25
negative regulation of DNA binding	-0.18	0.3	-10000	0	-0.64	138	138
stress fiber formation	-0.055	0.18	0.25	3	-0.38	93	96
GZMB	-0.11	0.22	-10000	0	-0.46	140	140
CASP1	-0.007	0.09	-10000	0	-0.36	27	27
LMNB1	-0.022	0.1	-10000	0	-0.39	17	17
APP	0.006	0.045	-10000	0	-0.42	1	1
TNFRSF1A	0.001	0.085	-10000	0	-0.55	12	12
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.001	0.064	-10000	0	-0.36	16	16
VIM	-0.075	0.18	0.23	6	-0.38	97	103
LMNA	-0.013	0.093	-10000	0	-0.39	9	9
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.028	0.12	-10000	0	-0.4	18	18
LRDD	0.006	0.069	-10000	0	-0.58	7	7
SREBF1	-0.065	0.18	0.24	2	-0.38	102	104
APAF-1/Caspase 9	-0.006	0.042	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	-0.043	0.14	0.21	1	-0.31	96	97
CFL2	-0.044	0.17	0.24	3	-0.37	89	92
GAS2	-0.064	0.18	0.24	2	-0.39	98	100
positive regulation of apoptosis	-0.014	0.097	-10000	0	-0.4	10	10
PRF1	-0.062	0.19	-10000	0	-0.54	71	71

×

Glypican 1 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
GPC1/FGF2 dimer/FGFR1 dimer	-0.005	0.043	-10000	0	-0.45	3	3
fibroblast growth factor receptor signaling pathway	-0.005	0.043	-10000	0	-0.44	3	3
LAMA1	-0.063	0.2	-10000	0	-0.57	68	68
PRNP	0.014	0	-10000	0	-10000	0	0
GPC1/SLIT2	-0.095	0.17	-10000	0	-0.38	128	128
SMAD2	0.03	0.044	-10000	0	-0.41	2	2
GPC1/PrPc/Cu2+	-0.002	0.025	-10000	0	-0.29	4	4
GPC1/Laminin alpha1	-0.057	0.14	-10000	0	-0.42	70	70
TDGF1	-0.077	0.21	-10000	0	-0.57	81	81
CRIPTO/GPC1	-0.066	0.15	-10000	0	-0.42	82	82
APP/GPC1	-0.003	0.03	-10000	0	-0.34	4	4
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.032	0.15	-10000	0	-0.35	84	84
FLT1	0.013	0.027	-10000	0	-0.59	1	1
GPC1/TGFB/TGFBR1/TGFBR2	-0.006	0.045	-10000	0	-0.31	10	10
SERPINC1	-0.005	0.09	-10000	0	-0.49	17	17
FYN	-0.029	0.14	-10000	0	-0.34	82	82
FGR	-0.031	0.14	-10000	0	-0.34	85	85
positive regulation of MAPKKK cascade	-0.071	0.19	-10000	0	-0.46	71	71
SLIT2	-0.12	0.24	-10000	0	-0.54	125	125
GPC1/NRG	-0.13	0.19	-10000	0	-0.4	166	166
NRG1	-0.17	0.27	-10000	0	-0.55	164	164
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.015	0.065	-10000	0	-0.29	26	26
LYN	-0.036	0.15	-10000	0	-0.35	90	90
mol:Spermine	0.01	0.032	-10000	0	-0.35	4	4
cell growth	-0.005	0.043	-10000	0	-0.44	3	3
BMP signaling pathway	-0.01	0.044	0.49	4	-10000	0	4
SRC	-0.029	0.14	-10000	0	-0.34	82	82
TGFBR1	0.012	0.035	-10000	0	-0.54	2	2
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.087	0.2	-10000	0	-0.51	92	92
GPC1	0.01	0.044	-10000	0	-0.49	4	4
TGFBR1 (dimer)	0.012	0.035	-10000	0	-0.54	2	2
VEGFA	-0.007	0.1	-10000	0	-0.49	22	22
BLK	-0.1	0.19	-10000	0	-0.35	180	180
HCK	-0.042	0.16	-10000	0	-0.36	96	96
FGF2	0.011	0.044	-10000	0	-0.56	3	3
FGFR1	0.013	0.027	-10000	0	-0.59	1	1
VEGFR1 homodimer	0.013	0.027	-10000	0	-0.59	1	1
TGFBR2	0.009	0.049	-10000	0	-0.49	5	5
cell death	-0.003	0.03	-10000	0	-0.34	4	4
ATIII/GPC1	-0.014	0.067	-10000	0	-0.34	21	21
PLA2G2A/GPC1	-0.066	0.14	-10000	0	-0.37	93	93
LCK	-0.087	0.19	-10000	0	-0.37	152	152
neuron differentiation	-0.13	0.19	-10000	0	-0.4	166	166
PrPc/Cu2+	0	0	-10000	0	-10000	0	0
APP	0.014	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.009	0.049	-10000	0	-0.49	5	5

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.18	0.39	-10000	0	-1	61	61
PCK1	-0.24	0.43	-10000	0	-1.1	71	71
HNF4A	-0.21	0.43	-10000	0	-1.1	66	66
KCNJ11	-0.25	0.51	-10000	0	-1.2	93	93
AKT1	-0.076	0.16	-10000	0	-0.42	31	31
response to starvation	-0.002	0.023	-10000	0	-10000	0	0
DLK1	-0.25	0.46	-10000	0	-1	92	92
NKX2-1	-0.076	0.22	-10000	0	-0.77	16	16
ACADM	-0.18	0.39	-10000	0	-0.97	66	66
TAT	-0.23	0.42	-10000	0	-1.1	72	72
CEBPB	-0.005	0.1	-10000	0	-0.57	17	17
CEBPA	-0.015	0.13	-10000	0	-0.56	27	27
TTR	-0.15	0.28	-10000	0	-0.9	32	32
PKLR	-0.19	0.4	-10000	0	-1	66	66
APOA1	-0.24	0.48	-10000	0	-1.2	70	70
CPT1C	-0.18	0.39	-10000	0	-0.98	66	66
ALAS1	-0.062	0.2	-10000	0	-0.83	2	2
TFRC	-0.17	0.31	-10000	0	-0.79	53	53
FOXF1	-0.005	0.094	-10000	0	-0.51	16	16
NF1	0.02	0.038	-10000	0	-0.59	2	2
HNF1A (dimer)	0.012	0.039	-10000	0	-0.65	1	1
CPT1A	-0.18	0.39	-10000	0	-0.97	69	69
HMGCS1	-0.18	0.39	-10000	0	-0.99	65	65
NR3C1	-0.023	0.077	-10000	0	-0.3	1	1
CPT1B	-0.2	0.41	-10000	0	-0.99	77	77
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.01	0.024	-10000	0	-10000	0	0
GCK	-0.25	0.48	-10000	0	-1.1	105	105
CREB1	-0.003	0.054	-10000	0	-10000	0	0
IGFBP1	-0.26	0.5	-10000	0	-1.3	85	85
PDX1	-0.079	0.21	-10000	0	-0.68	12	12
UCP2	-0.2	0.42	-10000	0	-1	79	79
ALDOB	-0.2	0.44	-10000	0	-1.1	72	72
AFP	-0.09	0.17	-10000	0	-0.54	37	37
BDH1	-0.22	0.45	-10000	0	-1.1	81	81
HADH	-0.18	0.41	-10000	0	-1	65	65
F2	-0.21	0.43	-10000	0	-1.1	56	56
HNF1A	0.012	0.039	-10000	0	-0.66	1	1
G6PC	-0.067	0.21	-10000	0	-1.1	11	11
SLC2A2	-0.093	0.22	-10000	0	-0.66	11	11
INS	0.013	0.091	0.24	11	-0.56	5	16
FOXA1	-0.054	0.17	-10000	0	-0.51	52	52
FOXA3	-0.12	0.23	-10000	0	-0.52	109	109
FOXA2	-0.22	0.47	-10000	0	-1.1	82	82
ABCC8	-0.27	0.53	-10000	0	-1.2	94	94
ALB	-0.13	0.3	-10000	0	-1	43	43

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.014	0	-9999	-10000	0	0
GNAT1/GTP	-0.021	0.085	-9999	-0.36	31	31
Metarhodopsin II/Arrestin	-0.03	0.095	-9999	-0.32	49	49
PDE6G/GNAT1/GTP	-0.045	0.12	-9999	-0.33	70	70
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	-0.019	0.12	-9999	-0.5	31	31
GRK1	0.012	0.022	-9999	-0.49	1	1
CNG Channel	-0.19	0.2	-9999	-0.55	82	82
mol:Na +	-0.2	0.2	-9999	-0.52	102	102
mol:ADP	0.012	0.022	-9999	-0.49	1	1
RGS9-1/Gbeta5/R9AP	-0.038	0.12	-9999	-0.37	53	53
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.2	0.21	-9999	-0.54	102	102
CNGB1	-0.18	0.26	-9999	-0.53	181	181
RDH5	-0.018	0.12	-9999	-0.5	33	33
SAG	0.002	0.022	-9999	-0.49	1	1
mol:Ca2+	-0.17	0.21	-9999	-0.5	102	102
Na + (4 Units)	-0.18	0.18	-9999	-0.48	102	102
RGS9	-0.039	0.17	-9999	-0.58	46	46
GNB1/GNGT1	-0.001	0.021	-9999	-0.34	2	2
GNAT1/GDP	-0.046	0.11	-9999	-0.32	51	51
GUCY2D	-0.006	0.087	-9999	-0.49	16	16
GNGT1	-0.001	0.031	-9999	-0.49	2	2
GUCY2F	0.005	0.049	-9999	-0.49	5	5
GNB5	0.014	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.061	0.16	-9999	-0.37	74	74
mol:11-cis-retinal	-0.018	0.12	-9999	-0.5	33	33
mol:cGMP	-0.082	0.17	-9999	-0.37	104	104
GNB1	0.014	0	-9999	-10000	0	0
Rhodopsin	-0.057	0.13	-9999	-0.36	81	81
SLC24A1	0.014	0	-9999	-10000	0	0
CNGA1	-0.057	0.19	-9999	-0.56	64	64
Metarhodopsin II	-0.027	0.083	-9999	-0.28	50	50
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.11	0.17	-9999	-0.4	104	104
RGS9BP	0.002	0.085	-9999	-0.57	11	11
Metarhodopsin II/Transducin	-0.011	0.073	-9999	-0.3	14	14
GCAP Family/Ca ++	-0.1	0.17	-9999	-0.34	153	153
PDE6A/B	-0.069	0.16	-9999	-0.4	90	90
mol:Pi	-0.038	0.12	-9999	-0.37	53	53
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.017	0.067	-9999	-0.27	32	32
PDE6B	-0.034	0.16	-9999	-0.54	45	45
PDE6A	-0.039	0.16	-9999	-0.53	50	50
PDE6G	-0.032	0.16	-9999	-0.56	42	42
RHO	-0.039	0.16	-9999	-0.52	49	49
PDE6	-0.095	0.16	-9999	-0.56	31	31
GUCA1A	-0.14	0.25	-9999	-0.54	141	141
GC2/GCAP Family	-0.1	0.16	-9999	-0.38	96	96
GUCA1C	-0.013	0.091	-9999	-0.49	18	18
GUCA1B	-0.007	0.11	-9999	-0.59	18	18

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.1	0.23	-9999	-0.51	88	88
MAP3K8	-0.007	0.099	-9999	-0.51	19	19
FOS	-0.09	0.21	-9999	-0.5	84	84
PRKCA	0.011	0.028	-9999	-0.6	1	1
PTPN7	-0.12	0.24	-9999	-0.55	127	127
HRAS	0.014	0.001	-9999	-10000	0	0
PRKCB	-0.064	0.19	-9999	-0.52	73	73
NRAS	0.014	0.001	-9999	-10000	0	0
RAS family/GTP	0.023	0.017	-9999	-0.25	1	1
MAPK3	-0.073	0.18	-9999	-0.47	76	76
MAP2K1	-0.016	0.12	-9999	-0.45	27	27
ELK1	0.012	0.007	-9999	-10000	0	0
BRAF	-0.051	0.12	-9999	-0.44	41	41
mol:GTP	-0.001	0.002	-9999	-0.005	98	98
MAPK1	-0.073	0.18	-9999	-0.47	75	75
RAF1	-0.037	0.1	-9999	-0.43	25	25
KRAS	0.013	0.022	-9999	-0.49	1	1

×

HIF-1-alpha transcription factor network

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.018	0.49	-9999	-1.1	53	53
HDAC7	0.017	0.003	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.14	0.33	-9999	-0.89	55	55
SMAD4	0.016	0.004	-9999	-10000	0	0
ID2	-0.019	0.49	-9999	-1.1	53	53
AP1	-0.066	0.18	-9999	-0.42	102	102
ABCG2	-0.019	0.49	-9999	-1.1	55	55
HIF1A	0.024	0.093	-9999	-0.62	2	2
TFF3	-0.059	0.5	-9999	-1.1	61	61
GATA2	-0.003	0.1	-9999	-0.56	16	16
AKT1	0.018	0.1	-9999	-10000	0	0
response to hypoxia	0.001	0.11	-9999	-0.24	13	13
MCL1	-0.018	0.49	-9999	-1.1	51	51
NDRG1	-0.023	0.49	-9999	-1.1	54	54
SERPINE1	-0.093	0.54	-9999	-1.1	79	79
FECH	-0.018	0.49	-9999	-1.1	53	53
FURIN	-0.018	0.49	-9999	-1.1	53	53
NCOA2	-0.025	0.15	-9999	-0.59	35	35
EP300	0.033	0.18	-9999	-0.35	34	34
HMOX1	-0.028	0.5	-9999	-1.1	57	57
BHLHE40	-0.026	0.5	-9999	-1.1	56	56
BHLHE41	-0.026	0.5	-9999	-1.1	56	56
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.013	0.059	-9999	-0.4	6	6
ENG	0.087	0.13	-9999	-0.54	6	6
JUN	0.003	0.075	-9999	-0.5	11	11
RORA	-0.019	0.49	-9999	-1.1	53	53
ABCB1	-0.039	0.093	-9999	-1.1	2	2
TFRC	-0.024	0.5	-9999	-1.1	58	58
CXCR4	-0.03	0.5	-9999	-1.1	55	55
TF	-0.051	0.53	-9999	-1.1	65	65
CITED2	-0.019	0.49	-9999	-1.1	53	53
HIF1A/ARNT	-0.19	0.49	-9999	-1.3	60	60
LDHA	-0.03	0.09	-9999	-0.67	6	6
ETS1	-0.024	0.49	-9999	-1.1	56	56
PGK1	-0.018	0.49	-9999	-1.1	53	53
NOS2	-0.042	0.51	-9999	-1.1	60	60
ITGB2	-0.037	0.51	-9999	-1.1	57	57
ALDOA	-0.018	0.49	-9999	-1.1	53	53
Cbp/p300/CITED2	-0.088	0.5	-9999	-1.2	54	54
FOS	-0.096	0.22	-9999	-0.55	101	101
HK2	-0.03	0.5	-9999	-1.1	56	56
SP1	0.024	0.005	-9999	-10000	0	0
GCK	-0.066	0.47	-9999	-1.2	64	64
HK1	-0.018	0.49	-9999	-1.1	55	55
NPM1	-0.018	0.49	-9999	-1.1	53	53
EGLN1	-0.018	0.49	-9999	-1.1	53	53
CREB1	0.023	0.003	-9999	-10000	0	0
PGM1	-0.018	0.49	-9999	-1.1	53	53
SMAD3	0.016	0.004	-9999	-10000	0	0
EDN1	-0.045	0.32	-9999	-1.1	25	25
IGFBP1	-0.076	0.52	-9999	-1.1	64	64
VEGFA	0.016	0.41	-9999	-0.88	41	41
HIF1A/JAB1	-0.008	0.037	-9999	-0.46	2	2
CP	-0.1	0.55	-9999	-1.1	75	75
CXCL12	-0.023	0.49	-9999	-1.1	56	56
COPS5	0.015	0.003	-9999	-10000	0	0
SMAD3/SMAD4	0	0.004	-9999	-10000	0	0
BNIP3	-0.019	0.49	-9999	-1.1	53	53
EGLN3	-0.024	0.5	-9999	-1.1	53	53
CA9	-0.054	0.52	-9999	-1.2	60	60
TERT	-0.085	0.51	-9999	-1.1	69	69
ENO1	-0.018	0.49	-9999	-1.1	53	53
PFKL	-0.018	0.49	-9999	-1.1	53	53
NCOA1	0.015	0.001	-9999	-10000	0	0
ADM	-0.053	0.52	-9999	-1.1	64	64
ARNT	0.014	0.087	-9999	-0.65	1	1
HNF4A	-0.043	0.14	-9999	-0.49	42	42
ADFP	-0.069	0.47	-9999	-1.1	57	57
SLC2A1	0.024	0.39	-9999	-0.84	35	35
LEP	-0.054	0.48	-9999	-1.1	55	55
HIF1A/ARNT/Cbp/p300	-0.15	0.35	-9999	-0.92	57	57
EPO	0.024	0.36	-9999	-0.94	21	21
CREBBP	0.036	0.17	-9999	-0.33	30	30
HIF1A/ARNT/Cbp/p300/HDAC7	-0.14	0.34	-9999	-0.92	54	54
PFKFB3	-0.02	0.49	-9999	-1.1	54	54
NT5E	-0.026	0.5	-9999	-1.1	56	56

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.062	0.2	-9999	-0.58	63	63
PDGF/PDGFRA/CRKL	-0.05	0.14	-9999	-0.41	64	64
positive regulation of JUN kinase activity	-0.039	0.1	-9999	-0.32	53	53
CRKL	0.013	0.022	-9999	-0.49	1	1
PDGF/PDGFRA/Caveolin-3	-0.057	0.15	-9999	-0.42	74	74
AP1	-0.17	0.32	-9999	-0.9	74	74
mol:IP3	-0.036	0.15	-9999	-0.42	63	63
PLCG1	-0.036	0.15	-9999	-0.42	63	63
PDGF/PDGFRA/alphaV Integrin	-0.05	0.14	-9999	-0.41	63	63
RAPGEF1	0.014	0	-9999	-10000	0	0
CRK	0.014	0	-9999	-10000	0	0
mol:Ca2+	-0.036	0.15	-9999	-0.42	63	63
CAV3	-0.007	0.084	-9999	-0.49	15	15
CAV1	-0.05	0.17	-9999	-0.49	65	65
SHC/Grb2/SOS1	-0.037	0.11	-9999	-0.32	53	53
PDGF/PDGFRA/Shf	-0.052	0.14	-9999	-0.42	64	64
FOS	-0.14	0.34	-9999	-0.89	74	74
JUN	-0.02	0.061	-9999	-0.4	11	11
oligodendrocyte development	-0.05	0.14	-9999	-0.41	63	63
GRB2	0.013	0.022	-9999	-0.49	1	1
PIK3R1	0.014	0	-9999	-10000	0	0
mol:DAG	-0.036	0.15	-9999	-0.42	63	63
PDGF/PDGFRA	-0.062	0.2	-9999	-0.58	63	63
actin cytoskeleton reorganization	-0.049	0.13	-9999	-0.41	63	63
SRF	0.028	0.01	-9999	-10000	0	0
SHC1	0.009	0.049	-9999	-0.49	5	5
PI3K	-0.042	0.11	-9999	-0.34	58	58
PDGF/PDGFRA/Crk/C3G	-0.041	0.11	-9999	-0.34	57	57
JAK1	-0.03	0.14	-9999	-0.41	63	63
ELK1/SRF	-0.001	0.11	-9999	-0.36	11	11
SHB	0.014	0	-9999	-10000	0	0
SHF	0.009	0.053	-9999	-0.59	4	4
CSNK2A1	0.014	0.022	-9999	-10000	0	0
GO:0007205	-0.037	0.15	-9999	-0.44	63	63
SOS1	0.014	0	-9999	-10000	0	0
Ras protein signal transduction	-0.039	0.1	-9999	-0.32	53	53
PDGF/PDGFRA/SHB	-0.049	0.13	-9999	-0.41	63	63
PDGF/PDGFRA/Caveolin-1	-0.093	0.18	-9999	-0.41	118	118
ITGAV	0.013	0.027	-9999	-0.59	1	1
ELK1	-0.029	0.14	-9999	-0.39	57	57
PIK3CA	0.013	0.027	-9999	-0.59	1	1
PDGF/PDGFRA/Crk	-0.049	0.13	-9999	-0.41	63	63
JAK-STAT cascade	-0.03	0.14	-9999	-0.41	63	63
cell proliferation	-0.052	0.14	-9999	-0.42	64	64

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.021	0.082	-9999	-0.34	32	32
ARNO/beta Arrestin1-2	-0.024	0.084	-9999	-0.53	7	7
EGFR	-0.083	0.21	-9999	-0.55	89	89
EPHA2	-0.015	0.12	-9999	-0.5	30	30
USP6	0.004	0.069	-9999	-0.49	10	10
IQSEC1	0.005	0.069	-9999	-0.51	9	9
EGFR/EGFR/EGF/EGF	-0.11	0.2	-9999	-0.43	132	132
ARRB2	0.009	0.037	-9999	-10000	0	0
mol:GTP	0.004	0.045	-9999	-0.16	24	24
ARRB1	-0.003	0.1	-9999	-0.59	15	15
FBXO8	0.013	0.027	-9999	-0.59	1	1
TSHR	-0.2	0.27	-9999	-0.54	196	196
EGF	-0.05	0.18	-9999	-0.56	58	58
somatostatin receptor activity	0	0	-9999	-0.001	74	74
ARAP2	-0.008	0.11	-9999	-0.59	19	19
mol:GDP	-0.071	0.12	-9999	-0.29	79	79
mol:PI-3-4-5-P3	0	0	-9999	-0.001	37	37
ITGA2B	-0.043	0.17	-9999	-0.57	50	50
ARF6	0.014	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.017	0.066	-9999	-0.4	3	3
ADAP1	-0.021	0.14	-9999	-0.55	32	32
KIF13B	0.014	0	-9999	-10000	0	0
HGF/MET	-0.17	0.23	-9999	-0.43	204	204
PXN	0.014	0	-9999	-10000	0	0
ARF6/GTP	-0.063	0.12	-9999	-0.28	70	70
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.097	0.17	-9999	-0.41	92	92
ADRB2	-0.015	0.13	-9999	-0.59	25	25
receptor agonist activity	0	0	-9999	0	77	77
actin filament binding	0	0	-9999	-0.001	80	80
SRC	0.014	0	-9999	-10000	0	0
ITGB3	-0.052	0.18	-9999	-0.51	65	65
GNAQ	0.014	0	-9999	-10000	0	0
EFA6/PI-4-5-P2	0	0	-9999	-0.001	51	51
ARF6/GDP	-0.007	0.1	-9999	-0.39	17	17
ARF6/GDP/GULP/ACAP1	-0.11	0.16	-9999	-0.4	89	89
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.062	0.13	-9999	-0.35	54	54
ACAP1	-0.03	0.14	-9999	-0.5	44	44
ACAP2	0.013	0.027	-9999	-0.59	1	1
LHCGR/beta Arrestin2	0.002	0.052	-9999	-0.28	16	16
EFNA1	0.01	0.044	-9999	-0.49	4	4
HGF	-0.079	0.2	-9999	-0.51	91	91
CYTH3	0.012	0	-9999	-10000	0	0
CYTH2	0.009	0.002	-9999	-10000	0	0
NCK1	0.013	0.027	-9999	-0.59	1	1
fibronectin binding	0	0	-9999	0	69	69
endosomal lumen acidification	0	0	-9999	0	77	77
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.05	0.18	-9999	-0.57	57	57
GNAQ/ARNO	0.014	0.008	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	39	39
MET	-0.15	0.25	-9999	-0.54	151	151
GNA14	-0.014	0.12	-9999	-0.56	25	25
GNA15	-0.007	0.11	-9999	-0.57	19	19
GIT1	0.014	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	57	57
GNA11	0.004	0.08	-9999	-0.59	9	9
LHCGR	-0.007	0.087	-9999	-0.49	16	16
AGTR1	-0.033	0.16	-9999	-0.55	43	43
desensitization of G-protein coupled receptor protein signaling pathway	0.002	0.051	-9999	-0.28	16	16
IPCEF1/ARNO	-0.057	0.14	-9999	-0.48	15	15
alphaIIb/beta3 Integrin	-0.084	0.17	-9999	-0.41	107	107

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.11	0.17	-10000	0	-0.38	151	151
CRKL	-0.046	0.13	-10000	0	-0.48	10	10
mol:PIP3	-0.018	0.024	0.52	1	-10000	0	1
AKT1	0.003	0.027	0.37	1	-0.34	2	3
PTK2B	-0.009	0.11	-10000	0	-0.49	24	24
RAPGEF1	-0.036	0.12	-10000	0	-0.44	10	10
RANBP10	0.014	0	-10000	0	-10000	0	0
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
HGF/MET/SHIP2	-0.14	0.19	-10000	0	-0.44	110	110
MAP3K5	-0.04	0.13	-10000	0	-0.44	20	20
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.13	0.17	-10000	0	-0.39	110	110
AP1	-0.09	0.17	-10000	0	-0.4	102	102
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.009	0.049	-10000	0	-0.49	5	5
apoptosis	-0.1	0.25	-10000	0	-0.77	57	57
STAT3 (dimer)	-0.05	0.13	-10000	0	-0.42	15	15
GAB1/CRKL/SHP2/PI3K	-0.059	0.094	-10000	0	-0.42	10	10
INPP5D	0.008	0.06	-10000	0	-0.54	6	6
CBL/CRK	-0.036	0.12	-10000	0	-0.44	10	10
PTPN11	0.014	0	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.014	0	-10000	0	-10000	0	0
PTEN	0.013	0.027	-10000	0	-0.59	1	1
ELK1	-0.059	0.092	-10000	0	-0.2	151	151
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.049	0.071	-10000	0	-0.31	10	10
PAK1	-0.015	0.08	0.34	1	-0.27	19	20
HGF/MET/RANBP10	-0.14	0.19	-10000	0	-0.36	204	204
HRAS	-0.1	0.23	-10000	0	-0.64	67	67
DOCK1	-0.039	0.12	-10000	0	-0.44	10	10
GAB1	-0.057	0.13	-10000	0	-0.31	73	73
CRK	-0.046	0.13	-10000	0	-0.48	10	10
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.13	0.22	-10000	0	-0.59	81	81
JUN	0.003	0.074	-10000	0	-0.5	11	11
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.075	0.13	-10000	0	-0.28	110	110
PIK3R1	0.014	0	-10000	0	-10000	0	0
cell morphogenesis	-0.021	0.14	-10000	0	-0.46	9	9
GRB2/SHC	-0.052	0.12	-10000	0	-0.42	14	14
FOS	-0.096	0.22	-10000	0	-0.55	101	101
GLMN	0	0	-10000	0	-10000	0	0
cell motility	-0.059	0.092	-10000	0	-0.2	151	151
HGF/MET/MUC20	-0.15	0.2	-10000	0	-0.37	204	204
cell migration	-0.052	0.12	-10000	0	-0.41	14	14
GRB2	0.013	0.022	-10000	0	-0.49	1	1
CBL	0.014	0	-10000	0	-10000	0	0
MET/RANBP10	-0.11	0.17	-10000	0	-0.38	151	151
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.062	0.14	-10000	0	-0.34	39	39
MET/MUC20	-0.11	0.18	-10000	0	-0.39	151	151
RAP1B	-0.027	0.12	-10000	0	-0.42	9	9
RAP1A	-0.026	0.12	-10000	0	-0.42	9	9
HGF/MET/RANBP9	-0.14	0.19	-10000	0	-0.44	110	110
RAF1	-0.091	0.22	-10000	0	-0.6	67	67
STAT3	-0.051	0.13	-10000	0	-0.42	15	15
cell proliferation	-0.063	0.18	-10000	0	-0.4	77	77
RPS6KB1	-0.02	0.049	-10000	0	-10000	0	0
MAPK3	-0.059	0.083	-10000	0	-10000	0	0
MAPK1	-0.059	0.083	-10000	0	-10000	0	0
RANBP9	0.014	0	-10000	0	-10000	0	0
MAPK8	-0.025	0.14	-10000	0	-0.44	26	26
SRC	-0.05	0.13	-10000	0	-0.42	15	15
PI3K	-0.05	0.11	-10000	0	-0.39	10	10
MET/Glomulin	-0.09	0.16	-10000	0	-0.34	151	151
SOS1	0.014	0	-10000	0	-10000	0	0
MAP2K1	-0.077	0.2	-10000	0	-0.55	66	66
MET	-0.15	0.25	-10000	0	-0.54	151	151
MAP4K1	-0.047	0.14	-10000	0	-0.44	18	18
PTK2	0.014	0	-10000	0	-10000	0	0
MAP2K2	-0.076	0.2	-10000	0	-0.55	66	66
BAD	0.01	0.025	0.34	1	-0.31	2	3
MAP2K4	-0.03	0.13	-10000	0	-0.42	19	19
SHP2/GRB2/SOS1/GAB1	-0.089	0.14	-10000	0	-0.38	68	68
INPPL1	0.014	0	-10000	0	-10000	0	0
PXN	0.014	0	-10000	0	-10000	0	0
SH3KBP1	0.014	0	-10000	0	-10000	0	0
HGS	-0.061	0.12	-10000	0	-0.27	96	96
PLCgamma1/PKC	0	0	-10000	0	-10000	0	0
HGF	-0.079	0.2	-10000	0	-0.51	91	91
RASA1	0.014	0	-10000	0	-10000	0	0
NCK1	0.013	0.027	-10000	0	-0.59	1	1
PTPRJ	0.013	0.022	-10000	0	-0.49	1	1
NCK/PLCgamma1	-0.05	0.12	-10000	0	-0.25	96	96
PDPK1	-0.007	0.03	0.41	1	-0.37	2	3
HGF/MET/SHIP	-0.15	0.2	-10000	0	-0.44	114	114

×

p75(NTR)-mediated signaling

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
Sortilin/TRAF6	-0.002	0.027	-10000	0	-0.43	2	2
Necdin/E2F1	-0.049	0.14	-10000	0	-0.41	62	62
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.077	0.14	-10000	0	-0.34	83	83
NGF (dimer)/p75(NTR)/BEX1	-0.11	0.18	-10000	0	-0.37	147	147
NT-4/5 (dimer)/p75(NTR)	-0.066	0.15	-10000	0	-0.4	85	85
IKBKB	0.014	0	-10000	0	-10000	0	0
AKT1	-0.045	0.16	-10000	0	-0.56	15	15
IKBKG	0.014	0	-10000	0	-10000	0	0
BDNF	-0.08	0.2	-10000	0	-0.51	93	93
MGDIs/NGR/p75(NTR)/LINGO1	-0.093	0.18	-10000	0	-0.38	124	124
FURIN	0.014	0	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.098	0.16	-10000	0	-0.34	150	150
LINGO1	-0.019	0.14	-10000	0	-0.59	28	28
Sortilin/TRAF6/NRIF	-0.001	0.015	-10000	0	-10000	0	0
proBDNF (dimer)	-0.079	0.2	-10000	0	-0.5	93	93
NTRK1	-0.008	0.11	-10000	0	-0.52	22	22
RTN4R	-0.036	0.16	-10000	0	-0.56	45	45
neuron apoptosis	-0.062	0.17	-10000	0	-0.52	27	27
IRAK1	0.014	0	-10000	0	-10000	0	0
SHC1	-0.074	0.18	-10000	0	-0.36	138	138
ARHGDIA	0.014	0	-10000	0	-10000	0	0
RhoA/GTP	0	0	-10000	0	-10000	0	0
Gamma Secretase	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.089	0.16	-10000	0	-0.37	91	91
MAGEH1	0.004	0.079	-10000	0	-0.59	9	9
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.11	0.18	-10000	0	-0.4	109	109
Mammalian IAPs/DIABLO	-0.024	0.08	-10000	0	-0.32	25	25
proNGF (dimer)	-0.071	0.2	-10000	0	-0.56	77	77
MAGED1	0.014	0	-10000	0	-10000	0	0
APP	0.014	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.011	0.09	-10000	0	-0.5	17	17
ZNF274	0.014	0	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.052	0.15	-10000	0	-0.34	82	82
NGF	-0.071	0.2	-10000	0	-0.56	77	77
cell cycle arrest	-0.074	0.14	-10000	0	-0.53	16	16
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.032	0.13	-10000	0	-0.43	20	20
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.056	0.13	-10000	0	-0.33	86	86
NCSTN	0.014	0	-10000	0	-10000	0	0
mol:GTP	-0.093	0.17	-10000	0	-0.4	85	85
PSENEN	0.014	0	-10000	0	-10000	0	0
mol:ceramide	-0.056	0.16	-10000	0	-0.36	83	83
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.02	0.12	-10000	0	-0.4	20	20
p75(NTR)/beta APP	-0.054	0.14	-10000	0	-0.38	73	73
BEX1	-0.007	0.11	-10000	0	-0.59	18	18
mol:GDP	-0.081	0.18	-10000	0	-0.37	135	135
NGF (dimer)	-0.13	0.18	-10000	0	-0.38	127	127
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.083	0.16	-10000	0	-0.4	81	81
PIK3R1	0.014	0	-10000	0	-10000	0	0
RAC1/GTP	-0.08	0.14	-10000	0	-0.31	135	135
MYD88	0.004	0.077	-10000	0	-0.57	9	9
CHUK	0.014	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.094	0.17	-10000	0	-0.4	85	85
RHOB	0.011	0.038	-10000	0	-0.49	3	3
RHOA	0.014	0	-10000	0	-10000	0	0
MAGE-G1/E2F1	-0.02	0.082	-10000	0	-0.36	28	28
NT3 (dimer)	-0.008	0.092	-10000	0	-0.49	18	18
TP53	-0.048	0.16	-10000	0	-0.51	25	25
PRDM4	-0.057	0.16	-10000	0	-0.36	83	83
BDNF (dimer)	-0.16	0.2	-10000	0	-0.44	124	124
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
SORT1	0.013	0.027	-10000	0	-0.59	1	1
activation of caspase activity	-0.076	0.14	-10000	0	-0.33	83	83
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.085	0.15	-10000	0	-0.37	84	84
RHOC	0.011	0.041	-10000	0	-0.52	3	3
XIAP	0.014	0	-10000	0	-10000	0	0
MAPK10	-0.042	0.16	-10000	0	-0.48	30	30
DIABLO	0.014	0	-10000	0	-10000	0	0
SMPD2	-0.057	0.16	-10000	0	-0.36	83	83
APH1B	0.014	0	-10000	0	-10000	0	0
APH1A	0.014	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.094	0.17	-10000	0	-0.36	136	136
PSEN1	0.014	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	-0.001	0.015	-10000	0	-0.34	1	1
NT3 (dimer)/p75(NTR)	-0.066	0.15	-10000	0	-0.39	87	87
MAPK8	-0.046	0.17	-10000	0	-0.46	33	33
MAPK9	-0.04	0.16	-10000	0	-0.48	26	26
APAF1	0.014	0	-10000	0	-10000	0	0
NTF3	-0.008	0.092	-10000	0	-0.49	18	18
NTF4	-0.011	0.09	-10000	0	-0.5	17	17
NDN	-0.028	0.16	-10000	0	-0.59	36	36
RAC1/GDP	0	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.072	0.13	-10000	0	-0.52	16	16
p75 CTF/Sortilin/TRAF6/NRIF	-0.005	0.044	-10000	0	-0.36	7	7
RhoA-B-C/GTP	-0.093	0.16	-10000	0	-0.4	85	85
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.08	0.14	-10000	0	-0.52	18	18
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.087	0.15	-10000	0	-0.39	56	56
PRKACB	0.014	0	-10000	0	-10000	0	0
proBDNF (dimer)/p75 ECD	-0.069	0.15	-10000	0	-0.37	96	96
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.033	0.16	-10000	0	-0.55	43	43
BIRC2	0.014	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.089	0.16	0.2	5	-0.38	89	94
BAD	-0.035	0.16	-10000	0	-0.45	29	29
RIPK2	0.014	0	-10000	0	-10000	0	0
NGFR	-0.064	0.19	-10000	0	-0.54	73	73
CYCS	-0.045	0.16	-10000	0	-0.55	15	15
ADAM17	0.007	0.065	-10000	0	-0.59	6	6
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.084	0.15	-10000	0	-0.37	83	83
BCL2L11	-0.035	0.16	-10000	0	-0.45	29	29
BDNF (dimer)/p75(NTR)	-0.12	0.19	-10000	0	-0.4	149	149
PI3K	-0.084	0.15	-10000	0	-0.37	82	82
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.084	0.15	-10000	0	-0.37	83	83
NDNL2	0.014	0	-10000	0	-10000	0	0
YWHAE	0.014	0	-10000	0	-10000	0	0
PRKCI	0.014	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.11	0.2	-10000	0	-0.43	135	135
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.084	0.15	-10000	0	-0.37	83	83
TRAF6	0.013	0.027	-10000	0	-0.59	1	1
RAC1	0.014	0	-10000	0	-10000	0	0
PRKCZ	-0.015	0.13	-10000	0	-0.55	27	27
PLG	-0.002	0.043	-10000	0	-0.49	4	4
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.091	0.19	-10000	0	-0.46	63	63
SQSTM1	0.014	0	-10000	0	-10000	0	0
NGFRAP1	0.014	0	-10000	0	-10000	0	0
CASP3	-0.03	0.15	-10000	0	-0.42	29	29
E2F1	-0.014	0.12	-10000	0	-0.51	28	28
CASP9	0.013	0.022	-10000	0	-0.49	1	1
IKK complex	-0.066	0.12	-10000	0	-0.5	18	18
NGF (dimer)/TRKA	-0.075	0.16	-10000	0	-0.4	95	95
MMP7	-0.16	0.26	-10000	0	-0.54	155	155
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.078	0.14	-10000	0	-0.55	16	16
MMP3	-0.036	0.14	-10000	0	-0.49	46	46
APAF-1/Caspase 9	-0.068	0.11	-10000	0	-0.45	21	21

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	-0.003	0.03	-10000	0	-0.34	4	4
PRKCZ	-0.015	0.13	-10000	0	-0.55	27	27
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.013	0.022	-10000	0	-0.49	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.078	0.12	-10000	0	-0.39	31	31
IRAK/TOLLIP	0.03	0.024	-10000	0	-10000	0	0
IKBKB	0.014	0	-10000	0	-10000	0	0
IKBKG	0.014	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.16	0.21	-10000	0	-0.41	207	207
IL1A	-0.093	0.22	-10000	0	-0.54	99	99
IL1B	-0.13	0.21	-10000	0	-0.4	190	190
IRAK/TRAF6/p62/Atypical PKCs	-0.014	0.057	-10000	0	-0.42	1	1
IL1R2	-0.12	0.24	-10000	0	-0.53	128	128
IL1R1	-0.032	0.15	-10000	0	-0.52	45	45
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.045	0.12	0.21	1	-0.39	25	26
TOLLIP	0.014	0	-10000	0	-10000	0	0
TICAM2	0	0.089	-10000	0	-0.58	12	12
MAP3K3	0.014	0	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0	0	-10000	0	-10000	0	0
IKK complex/ELKS	0.064	0.033	-10000	0	-10000	0	0
JUN	0.034	0.07	-10000	0	-0.45	4	4
MAP3K7	0.014	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.14	0.17	-10000	0	-0.54	49	49
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.11	0.17	-10000	0	-0.4	87	87
PIK3R1	0.014	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.099	0.16	-10000	0	-0.37	87	87
IL1 beta fragment/IL1R1/IL1RAP	-0.14	0.21	-10000	0	-0.43	119	119
NFKB1	0.014	0	-10000	0	-10000	0	0
MAPK8	0.032	0.059	-10000	0	-0.54	1	1
IRAK1	0.023	0.027	-10000	0	-0.28	4	4
IL1RN/IL1R1	-0.12	0.2	-10000	0	-0.42	144	144
IRAK4	0.013	0.022	-10000	0	-0.49	1	1
PRKCI	0.014	0	-10000	0	-10000	0	0
TRAF6	0.013	0.027	-10000	0	-0.59	1	1
PI3K	-0.001	0.019	-10000	0	-0.43	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.063	0.14	-10000	0	-0.38	44	44
CHUK	0.014	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.14	0.21	-10000	0	-0.43	119	119
IL1 beta/IL1R2	-0.19	0.23	-10000	0	-0.38	266	266
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.002	0.022	-10000	0	-0.28	1	1
NF kappa B1 p50/RelA	-0.12	0.15	-10000	0	-0.48	49	49
IRAK3	0.008	0.062	-10000	0	-0.56	6	6
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.14	0.18	-10000	0	-0.54	56	56
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.043	0.14	-10000	0	-0.38	31	31
IL1 alpha/IL1R1/IL1RAP	-0.12	0.18	-10000	0	-0.44	83	83
RELA	0.014	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.014	0	-10000	0	-10000	0	0
MYD88	0.004	0.077	-10000	0	-0.57	9	9
IRAK/TRAF6/MEKK3	0.037	0.027	-10000	0	-0.3	1	1
IL1RAP	-0.036	0.15	-10000	0	-0.51	50	50
UBE2N	0.014	0	-10000	0	-10000	0	0
IRAK/TRAF6	-0.11	0.15	-10000	0	-0.45	57	57
CASP1	-0.015	0.12	-10000	0	-0.53	28	28
IL1RN/IL1R2	-0.18	0.24	-10000	0	-0.45	201	201
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.13	0.21	-10000	0	-0.41	125	125
TMEM189-UBE2V1	0.004	0.044	-10000	0	-0.49	4	4
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.023	0.12	-10000	0	-0.41	23	23
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
IL1RN	-0.11	0.23	-10000	0	-0.53	119	119
TRAF6/TAK1/TAB1/TAB2	-0.002	0.023	-10000	0	-0.3	1	1
MAP2K6	0.033	0.029	-10000	0	-0.28	2	2

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.011	0.096	-9999	-0.37	32	32
NFATC2	-0.041	0.13	-9999	-0.36	76	76
NFATC3	0.012	0.032	-9999	-0.34	2	2
CD40LG	-0.15	0.29	-9999	-0.67	87	87
PTGS2	-0.18	0.32	-9999	-0.68	118	118
JUNB	-0.031	0.15	-9999	-0.52	44	44
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.005	0.027	-9999	-0.41	2	2
CaM/Ca2+	-0.005	0.027	-9999	-0.41	2	2
CALM1	0.01	0.036	-9999	-0.55	2	2
JUN	0.001	0.075	-9999	-0.5	11	11
mol:Ca2+	-0.005	0.01	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.001	0.003	-9999	-10000	0	0
FOSL1	-0.093	0.22	-9999	-0.53	101	101
CREM	0.012	0.035	-9999	-0.54	2	2
Jun/NFAT1-c-4/p21SNFT	-0.12	0.18	-9999	-0.52	59	59
FOS	-0.099	0.23	-9999	-0.56	101	101
IFNG	-0.13	0.27	-9999	-0.64	70	70
AP-1/NFAT1-c-4	-0.16	0.32	-9999	-0.71	93	93
FASLG	-0.14	0.28	-9999	-0.67	78	78
NFAT1-c-4/ICER1	-0.056	0.15	-9999	-0.44	41	41
IL2RA	-0.16	0.3	-9999	-0.68	89	89
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	-0.14	0.26	-9999	-0.64	67	67
JunB/Fra1/NFAT1-c-4	-0.14	0.2	-9999	-0.48	96	96
IL4	-0.13	0.26	-9999	-0.62	73	73
IL2	-0.008	0.015	-9999	-10000	0	0
IL3	-0.018	0.038	-9999	-0.75	1	1
FKBP1A	0.014	0	-9999	-10000	0	0
BATF3	-0.034	0.16	-9999	-0.53	45	45
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.013	0.027	-9999	-0.59	1	1

×

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	0.041	0.095	0.2	127	-10000	0	127
BUB1B	-0.058	0.14	-10000	0	-0.3	124	124
PLK1	-0.001	0.043	-10000	0	-0.13	31	31
PLK1S1	0.006	0.022	-10000	0	-0.11	2	2
KIF2A	0.006	0.048	-10000	0	-0.3	5	5
regulation of mitotic centrosome separation	-0.001	0.043	-10000	0	-0.13	31	31
GOLGA2	0.014	0	-10000	0	-10000	0	0
Hec1/SPC24	-0.13	0.24	-10000	0	-0.43	182	182
WEE1	-0.007	0.088	-10000	0	-0.35	22	22
cytokinesis	-0.11	0.21	-10000	0	-0.4	157	157
PP2A-alpha B56	-0.062	0.23	-10000	0	-0.67	60	60
AURKA	0.001	0.041	-10000	0	-0.15	23	23
PICH/PLK1	-0.031	0.16	-10000	0	-0.41	68	68
CENPE	-0.045	0.14	-10000	0	-0.32	94	94
RhoA/GTP	0	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.006	0.047	-10000	0	-0.3	5	5
PPP2CA	0.014	0	-10000	0	-10000	0	0
FZR1	0.014	0	-10000	0	-10000	0	0
TPX2	-0.019	0.08	-10000	0	-0.2	72	72
PAK1	-0.035	0.15	-10000	0	-0.5	49	49
SPC24	-0.12	0.24	-10000	0	-0.53	128	128
FBXW11	0.014	0	-10000	0	-10000	0	0
CLSPN	-0.037	0.11	-10000	0	-0.25	90	90
GORASP1	0.014	0	-10000	0	-10000	0	0
metaphase	0	0.004	-10000	0	-0.013	34	34
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0	0.022	-10000	0	-0.065	30	30
G2 phase of mitotic cell cycle	0	0.002	-10000	0	-0.009	15	15
STAG2	0.014	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.003	0.01	-10000	0	-10000	0	0
spindle elongation	-0.001	0.043	-10000	0	-0.13	31	31
ODF2	0.013	0.003	-10000	0	-10000	0	0
BUB1	-0.1	0.24	-10000	0	-0.74	60	60
TPT1	0.006	0.022	-10000	0	-0.13	1	1
CDC25C	-0.048	0.13	-10000	0	-0.31	89	89
CDC25B	0.014	0.003	-10000	0	-10000	0	0
SGOL1	-0.041	0.096	-10000	0	-0.2	127	127
RHOA	0.014	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.029	0.089	-10000	0	-0.31	40	40
CDC14B	0.012	0.001	-10000	0	-10000	0	0
CDC20	-0.1	0.23	-10000	0	-0.54	112	112
PLK1/PBIP1	-0.047	0.11	-10000	0	-0.32	70	70
mitosis	0.001	0.005	0.021	9	-0.022	1	10
FBXO5	0.004	0.05	-10000	0	-0.28	8	8
CDC2	0	0.004	-10000	0	-0.013	42	42
NDC80	-0.13	0.25	-10000	0	-0.55	136	136
metaphase plate congression	0.005	0.026	-10000	0	-0.14	2	2
ERCC6L	-0.056	0.14	-10000	0	-0.41	64	64
NLP/gamma Tubulin	0.003	0.025	-10000	0	-0.11	3	3
microtubule cytoskeleton organization	0.006	0.022	-10000	0	-0.13	1	1
G2/M transition DNA damage checkpoint	0	0.002	0.01	5	-10000	0	5
PPP1R12A	0.013	0.027	-10000	0	-0.59	1	1
interphase	0	0.002	0.01	5	-10000	0	5
PLK1/PRC1-2	-0.091	0.18	-10000	0	-0.34	169	169
GRASP65/GM130/RAB1/GTP/PLK1	-0.005	0.023	-10000	0	-10000	0	0
RAB1A	0.014	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.006	0.036	-10000	0	-0.2	2	2
mitotic prometaphase	-0.001	0.002	-10000	0	-0.013	3	3
proteasomal ubiquitin-dependent protein catabolic process	0.005	0.061	-10000	0	-10000	0	0
microtubule-based process	-0.094	0.17	-10000	0	-0.33	169	169
Golgi organization	-0.001	0.043	-10000	0	-0.13	31	31
Cohesin/SA2	-0.012	0.029	-10000	0	-0.22	2	2
PPP1CB/MYPT1	0.003	0.021	-10000	0	-0.43	1	1
KIF20A	-0.17	0.26	-10000	0	-0.55	169	169
APC/C/CDC20	-0.058	0.15	-10000	0	-0.33	112	112
PPP2R1A	0.014	0	-10000	0	-10000	0	0
chromosome segregation	-0.047	0.11	-10000	0	-0.32	70	70
PRC1	-0.006	0.1	-10000	0	-0.49	21	21
ECT2	-0.002	0.079	-10000	0	-0.35	21	21
C13orf34	0.006	0.036	-10000	0	-0.21	2	2
NUDC	0.005	0.026	-10000	0	-0.14	2	2
regulation of attachment of spindle microtubules to kinetochore	-0.058	0.14	-10000	0	-0.3	124	124
spindle assembly	0.002	0.035	-10000	0	-0.1	25	25
spindle stabilization	0.006	0.022	-10000	0	-0.11	2	2
APC/C/HCDH1	0.02	0.001	-10000	0	-10000	0	0
MKLP2/PLK1	-0.094	0.17	-10000	0	-0.33	169	169
CCNB1	-0.019	0.13	-10000	0	-0.49	34	34
PPP1CB	0.014	0.001	-10000	0	-10000	0	0
BTRC	0.014	0	-10000	0	-10000	0	0
ROCK2	-0.006	0.095	-10000	0	-0.44	21	21
TUBG1	0.006	0.022	-10000	0	-0.13	1	1
G2/M transition of mitotic cell cycle	-0.031	0.086	-10000	0	-0.3	40	40
MLF1IP	-0.043	0.14	-10000	0	-0.4	70	70
INCENP	0.011	0.027	-10000	0	-0.6	1	1

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	-0.018	0.12	-9999	-0.5	32	32
PLK4	-0.012	0.11	-9999	-0.5	26	26
regulation of centriole replication	-0.018	0.12	-9999	-0.36	57	57

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.021	0.099	-10000	0	-0.88	3	3
SMARCC2	0.015	0.011	-10000	0	-10000	0	0
SMARCC1	0.015	0.011	-10000	0	-10000	0	0
TBX21	-0.11	0.25	-10000	0	-0.7	62	62
SUMO2	0.013	0.013	-10000	0	-10000	0	0
STAT1 (dimer)	0	0.11	-10000	0	-0.58	16	16
FKBP4	0.014	0	-10000	0	-10000	0	0
FKBP5	-0.086	0.22	-10000	0	-0.56	90	90
GR alpha/HSP90/FKBP51/HSP90	0.022	0.16	0.29	24	-0.33	42	66
PRL	-0.046	0.094	-10000	0	-0.57	2	2
cortisol/GR alpha (dimer)/TIF2	0.18	0.24	0.52	104	-0.44	4	108
RELA	-0.063	0.097	-10000	0	-0.28	6	6
FGG	0.16	0.17	0.47	52	-0.48	2	54
GR beta/TIF2	0.063	0.16	0.33	27	-0.41	31	58
IFNG	-0.23	0.22	-10000	0	-0.65	46	46
apoptosis	-0.009	0.2	0.62	19	-0.7	2	21
CREB1	0.013	0.023	-10000	0	-10000	0	0
histone acetylation	-0.045	0.12	-10000	0	-0.38	33	33
BGLAP	-0.047	0.12	-10000	0	-0.66	6	6
GR/PKAc	0.087	0.093	0.3	24	-10000	0	24
NF kappa B1 p50/RelA	-0.11	0.18	-10000	0	-0.42	72	72
SMARCD1	0.015	0.011	-10000	0	-10000	0	0
MDM2	0.079	0.078	0.27	29	-10000	0	29
GATA3	-0.1	0.23	-10000	0	-0.53	115	115
AKT1	0.002	0.016	-10000	0	-10000	0	0
CSF2	-0.062	0.099	-10000	0	-0.5	3	3
GSK3B	0.012	0.03	-10000	0	-0.6	1	1
NR1I3	0.028	0.19	0.63	16	-0.68	3	19
CSN2	0.14	0.13	0.4	28	-10000	0	28
BRG1/BAF155/BAF170/BAF60A	0.039	0.038	-10000	0	-10000	0	0
NFATC1	-0.019	0.14	-10000	0	-0.57	31	31
POU2F1	0.013	0.028	-10000	0	-0.59	1	1
CDKN1A	-0.06	0.31	-10000	0	-1.4	21	21
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0	0.012	-10000	0	-10000	0	0
SFN	-0.11	0.23	-10000	0	-0.53	119	119
GR alpha/HSP90/FKBP51/HSP90/14-3-3	-0.04	0.19	0.29	12	-0.42	41	53
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.052	0.32	0.61	15	-0.8	54	69
JUN	-0.16	0.19	-10000	0	-0.51	69	69
IL4	-0.082	0.15	-10000	0	-0.54	30	30
CDK5R1	-0.023	0.14	-10000	0	-0.59	31	31
PRKACA	0.014	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.18	0.2	-10000	0	-0.48	117	117
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.031	0.15	0.29	24	-0.32	16	40
cortisol/GR alpha (monomer)	0.23	0.26	0.61	116	-10000	0	116
NCOA2	-0.027	0.15	-10000	0	-0.59	35	35
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.14	0.23	-10000	0	-0.59	101	101
AP-1/NFAT1-c-4	-0.31	0.31	-10000	0	-0.71	134	134
AFP	-0.12	0.18	-10000	0	-0.63	25	25
SUV420H1	0.014	0	-10000	0	-10000	0	0
IRF1	0.11	0.15	0.48	11	-0.49	3	14
TP53	-0.013	0.15	-10000	0	-0.53	33	33
PPP5C	0.014	0	-10000	0	-10000	0	0
KRT17	-0.43	0.48	-10000	0	-1	178	178
KRT14	-0.13	0.18	-10000	0	-0.5	71	71
TBP	0.023	0.016	-10000	0	-10000	0	0
CREBBP	0.031	0.061	-10000	0	-10000	0	0
HDAC1	0.004	0.054	-10000	0	-0.59	4	4
HDAC2	0.014	0.001	-10000	0	-10000	0	0
AP-1	-0.31	0.31	-10000	0	-0.71	136	136
MAPK14	0.013	0.011	-10000	0	-10000	0	0
MAPK10	0.008	0.055	-10000	0	-0.6	4	4
MAPK11	0.003	0.081	-10000	0	-0.59	9	9
KRT5	-0.4	0.45	-10000	0	-0.92	175	175
interleukin-1 receptor activity	0	0.001	-10000	0	-10000	0	0
NCOA1	0.017	0.009	-10000	0	-10000	0	0
STAT1	0	0.11	-10000	0	-0.59	16	16
CGA	-0.065	0.12	-10000	0	-0.46	15	15
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.081	0.11	0.35	20	-10000	0	20
MAPK3	0.013	0.012	-10000	0	-10000	0	0
MAPK1	0.013	0.011	-10000	0	-10000	0	0
ICAM1	-0.2	0.27	-10000	0	-0.69	82	82
NFKB1	-0.063	0.097	-10000	0	-0.26	14	14
MAPK8	-0.14	0.17	-10000	0	-0.48	62	62
MAPK9	0.013	0.011	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.013	0.2	0.63	19	-0.74	2	21
BAX	0.001	0.11	-10000	0	-10000	0	0
POMC	-0.13	0.24	-10000	0	-1.3	13	13
EP300	0.026	0.08	-10000	0	-0.57	4	4
cortisol/GR alpha (dimer)/p53	0.18	0.23	0.51	101	-0.67	1	102
proteasomal ubiquitin-dependent protein catabolic process	0.056	0.069	0.26	17	-10000	0	17
SGK1	0.05	0.25	-10000	0	-1.4	14	14
IL13	-0.23	0.24	-10000	0	-0.68	69	69
IL6	-0.28	0.38	-10000	0	-0.83	136	136
PRKACG	0.005	0.044	-10000	0	-0.49	4	4
IL5	-0.2	0.19	-10000	0	-0.67	27	27
IL2	-0.23	0.21	-10000	0	-0.67	41	41
CDK5	0.014	0.006	-10000	0	-10000	0	0
PRKACB	0.014	0	-10000	0	-10000	0	0
HSP90AA1	0.014	0	-10000	0	-10000	0	0
IL8	-0.32	0.41	-10000	0	-0.84	164	164
CDK5R1/CDK5	-0.021	0.1	-10000	0	-0.43	31	31
NF kappa B1 p50/RelA/PKAc	-0.056	0.13	-10000	0	-0.36	16	16
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.2	0.2	0.5	112	-10000	0	112
SMARCA4	0.015	0.011	-10000	0	-10000	0	0
chromatin remodeling	0.14	0.13	0.38	49	-0.36	1	50
NF kappa B1 p50/RelA/Cbp	-0.053	0.16	-10000	0	-0.46	17	17
JUN (dimer)	-0.16	0.19	-10000	0	-0.51	69	69
YWHAH	-0.01	0.11	-10000	0	-0.49	25	25
VIPR1	-0.12	0.26	-10000	0	-0.71	74	74
NR3C1	0.14	0.14	0.44	56	-10000	0	56
NR4A1	-0.019	0.14	-10000	0	-0.5	39	39
TIF2/SUV420H1	-0.029	0.11	-10000	0	-0.43	35	35
MAPKKK cascade	-0.009	0.2	0.62	19	-0.7	2	21
cortisol/GR alpha (dimer)/Src-1	0.21	0.21	0.53	112	-10000	0	112
PBX1	0.013	0.028	-10000	0	-0.59	1	1
POU1F1	0.004	0.024	-10000	0	-0.49	1	1
SELE	-0.28	0.36	-10000	0	-0.81	127	127
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.14	0.14	0.38	48	-0.36	1	49
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.2	0.2	0.5	112	-10000	0	112
mol:cortisol	0.12	0.15	0.34	122	-10000	0	122
MMP1	-0.12	0.16	-10000	0	-0.55	37	37

×

TCGA08_p53

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
CDKN2A	-0.074	0.17	-10000	0	-0.42	104	104
TP53	-0.034	0.089	0.19	3	-0.43	14	17
Senescence	-0.034	0.089	0.19	3	-0.43	14	17
Apoptosis	-0.034	0.089	0.19	3	-0.43	14	17
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.048	0.1	0.25	102	-0.26	2	104
MDM4	0.005	0.066	-10000	0	-0.49	9	9

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.051	0.12	-9999	-0.34	55	55
NF kappa B1 p50/RelA/I kappa B alpha	-0.041	0.089	-9999	-0.38	17	17
AP1	-0.12	0.17	-9999	-0.48	61	61
mol:PIP3	-0.098	0.15	-9999	-0.46	44	44
AKT1	0.018	0.099	-9999	-0.34	10	10
PTK2B	-0.018	0.1	-9999	-0.31	34	34
RHOA	0.008	0.063	-9999	-0.32	7	7
PIK3CB	0.014	0.001	-9999	-10000	0	0
mol:Ca2+	0.006	0.086	-9999	-0.37	9	9
MAGI3	0.002	0.084	-9999	-0.59	10	10
RELA	0.014	0	-9999	-10000	0	0
apoptosis	-0.043	0.13	-9999	-0.34	61	61
HRAS/GDP	0	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	-0.006	0.1	-9999	-0.33	24	24
NF kappa B1 p50/RelA	-0.069	0.13	-9999	-0.49	27	27
endothelial cell migration	-0.045	0.18	-9999	-0.44	73	73
ADCY4	-0.022	0.15	-9999	-0.41	57	57
ADCY5	-0.027	0.16	-9999	-0.42	64	64
ADCY6	-0.02	0.15	-9999	-0.41	56	56
ADCY7	-0.02	0.15	-9999	-0.41	56	56
ADCY1	-0.048	0.17	-9999	-0.43	65	65
ADCY2	-0.026	0.16	-9999	-0.42	60	60
ADCY3	-0.02	0.15	-9999	-0.41	56	56
ADCY8	-0.043	0.18	-9999	-0.48	63	63
ADCY9	-0.021	0.15	-9999	-0.42	56	56
GSK3B	-0.01	0.1	-9999	-0.32	25	25
arachidonic acid secretion	-0.012	0.14	-9999	-0.38	56	56
GNG2	0.009	0.053	-9999	-0.59	4	4
TRIP6	0.009	0.065	-9999	-0.28	14	14
GNAO1	-0.034	0.14	-9999	-0.35	81	81
HRAS	0.014	0	-9999	-10000	0	0
NFKBIA	-0.011	0.12	-9999	-0.4	27	27
GAB1	0.012	0.035	-9999	-0.54	2	2
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.003	0.082	-9999	-1	3	3
JUN	0.003	0.074	-9999	-0.5	11	11
LPA/LPA2/NHERF2	-0.011	0.054	-9999	-0.33	13	13
TIAM1	-0.006	0.11	-9999	-1.3	3	3
PIK3R1	0.014	0.001	-9999	-10000	0	0
mol:IP3	0.005	0.088	-9999	-0.38	9	9
PLCB3	0.019	0.053	-9999	-0.29	13	13
FOS	-0.096	0.22	-9999	-0.55	101	101
positive regulation of mitosis	-0.012	0.14	-9999	-0.38	56	56
LPA/LPA1-2-3	-0.08	0.14	-9999	-0.38	68	68
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0.001	-9999	-10000	0	0
BCAR1	0.013	0.027	-9999	-0.59	1	1
stress fiber formation	-0.021	0.12	-9999	-0.34	34	34
GNAZ	-0.03	0.14	-9999	-0.34	77	77
EGFR/PI3K-beta/Gab1	-0.1	0.15	-9999	-0.49	43	43
positive regulation of dendritic cell cytokine production	-0.08	0.14	-9999	-0.37	68	68
LPA/LPA2/MAGI-3	-0.017	0.07	-9999	-0.35	21	21
ARHGEF1	-0.01	0.12	-9999	-0.31	52	52
GNAI2	-0.03	0.14	-9999	-0.34	77	77
GNAI3	-0.03	0.14	-9999	-0.34	77	77
GNAI1	-0.042	0.15	-9999	-0.36	85	85
LPA/LPA3	-0.038	0.11	-9999	-0.36	50	50
LPA/LPA2	-0.013	0.062	-9999	-0.41	11	11
LPA/LPA1	-0.067	0.15	-9999	-0.41	77	77
HB-EGF/EGFR	-0.13	0.21	-9999	-0.37	201	201
HBEGF	-0.092	0.19	-9999	-0.38	148	148
mol:DAG	0.005	0.088	-9999	-0.38	9	9
cAMP biosynthetic process	-0.024	0.16	-9999	-0.42	56	56
NFKB1	0.014	0	-9999	-10000	0	0
SRC	0.014	0	-9999	-10000	0	0
GNB1	0.014	0.001	-9999	-10000	0	0
LYN	-0.015	0.13	-9999	-0.43	26	26
GNAQ	-0.008	0.084	-9999	-0.32	17	17
LPAR2	0.002	0.084	-9999	-0.56	11	11
LPAR3	-0.042	0.15	-9999	-0.49	50	50
LPAR1	-0.066	0.2	-9999	-0.57	69	69
IL8	-0.18	0.23	-9999	-0.46	174	174
PTK2	-0.045	0.15	-9999	-0.34	68	68
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.043	0.13	-9999	-0.34	61	61
EGFR	-0.083	0.21	-9999	-0.55	89	89
PLCG1	-0.009	0.09	-9999	-0.3	23	23
PLD2	-0.046	0.15	-9999	-0.35	67	67
G12/G13	-0.05	0.11	-9999	-0.34	52	52
PI3K-beta	-0.039	0.086	-9999	-0.38	12	12
cell migration	-0.026	0.055	-9999	-0.23	9	9
SLC9A3R2	0.012	0.031	-9999	-0.49	2	2
PXN	-0.022	0.12	-9999	-0.34	34	34
HRAS/GTP	-0.013	0.15	-9999	-0.39	56	56
RAC1	0.014	0	-9999	-10000	0	0
MMP9	-0.14	0.24	-9999	-0.52	144	144
PRKCE	0.003	0.077	-9999	-0.52	11	11
PRKCD	-0.003	0.11	-9999	-0.39	21	21
Gi(beta/gamma)	-0.015	0.14	-9999	-0.38	57	57
mol:LPA	-0.003	0.035	-9999	-0.19	8	8
TRIP6/p130 Cas/FAK1/Paxillin	-0.065	0.12	-9999	-0.46	20	20
MAPKKK cascade	-0.012	0.14	-9999	-0.38	56	56
contractile ring contraction involved in cytokinesis	0.008	0.062	-9999	-0.31	7	7
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.022	0.1	-9999	-0.32	35	35
GNA15	-0.019	0.099	-9999	-0.32	33	33
GNA12	0.013	0.027	-9999	-0.59	1	1
GNA13	0.014	0	-9999	-10000	0	0
MAPT	-0.007	0.11	-9999	-0.34	24	24
GNA11	-0.014	0.094	-9999	-0.32	26	26
Rac1/GTP	-0.003	0.09	-9999	-1.1	3	3
MMP2	-0.045	0.18	-9999	-0.44	73	73

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.035	0.16	-9999	-0.5	24	24
NF kappa B1 p50/RelA/I kappa B alpha	-0.012	0.16	-9999	-0.49	18	18
alphaV/beta3 Integrin/Osteopontin/Src	-0.067	0.14	-9999	-0.38	91	91
AP1	-0.08	0.22	-9999	-0.59	47	47
ILK	-0.044	0.17	-9999	-0.51	24	24
bone resorption	-0.077	0.23	-9999	-0.53	79	79
PTK2B	-0.009	0.11	-9999	-0.49	24	24
PYK2/p130Cas	-0.093	0.16	-9999	-0.5	43	43
ITGAV	0.016	0.027	-9999	-0.58	1	1
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.067	0.16	-9999	-0.42	83	83
alphaV/beta3 Integrin/Osteopontin	-0.093	0.16	-9999	-0.39	101	101
MAP3K1	-0.049	0.17	-9999	-0.5	31	31
JUN	0.003	0.074	-9999	-0.5	11	11
MAPK3	-0.037	0.17	-9999	-0.51	26	26
MAPK1	-0.037	0.17	-9999	-0.51	26	26
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0.014	0	-9999	-10000	0	0
MAPK8	-0.045	0.18	-9999	-0.48	38	38
ITGB3	-0.049	0.18	-9999	-0.51	65	65
NFKBIA	-0.028	0.17	-9999	-0.5	25	25
FOS	-0.095	0.22	-9999	-0.55	101	101
CD44	-0.057	0.19	-9999	-0.55	65	65
CHUK	0.014	0	-9999	-10000	0	0
PLAU	-0.067	0.27	-9999	-0.82	36	36
NF kappa B1 p50/RelA	-0.074	0.13	-9999	-0.53	17	17
BCAR1	0.013	0.027	-9999	-0.59	1	1
RELA	0.014	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.047	0.12	-9999	-0.36	66	66
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.06	0.19	-9999	-0.42	86	86
VAV3	-0.12	0.23	-9999	-0.57	71	71
MAP3K14	-0.046	0.17	-9999	-0.51	27	27
ROCK2	-0.011	0.12	-9999	-0.59	21	21
SPP1	-0.079	0.21	-9999	-0.53	90	90
RAC1	0.014	0	-9999	-10000	0	0
Rac1/GTP	-0.13	0.19	-9999	-0.52	70	70
MMP2	-0.067	0.21	-9999	-0.6	35	35

×

Nongenotropic Androgen signaling

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
PTK2	0.012	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.062	0.13	-10000	0	-0.3	111	111
regulation of S phase of mitotic cell cycle	-0.019	0.11	-10000	0	-0.26	72	72
GNAO1	0.008	0.059	-10000	0	-0.59	5	5
HRAS	0.014	0.001	-10000	0	-10000	0	0
SHBG/T-DHT	-0.007	0.055	-10000	0	-0.36	12	12
PELP1	0.014	0.001	-10000	0	-10000	0	0
AKT1	0.012	0	-10000	0	-10000	0	0
MAP2K1	-0.024	0.13	-10000	0	-0.37	24	24
T-DHT/AR	-0.084	0.17	-10000	0	-0.41	107	107
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	-10000	0	-0.006	97	97
GNAI2	0.014	0	-10000	0	-10000	0	0
GNAI3	0.014	0	-10000	0	-10000	0	0
GNAI1	-0.005	0.1	-10000	0	-0.59	16	16
mol:GDP	-0.077	0.16	-10000	0	-0.46	72	72
cell proliferation	-0.038	0.18	-10000	0	-0.42	63	63
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
FOS	-0.086	0.28	-10000	0	-0.78	63	63
mol:Ca2+	-0.01	0.019	-10000	0	-0.061	31	31
MAPK3	-0.03	0.15	-10000	0	-0.47	24	24
MAPK1	-0.014	0.09	-10000	0	-0.27	20	20
PIK3R1	0.014	0	-10000	0	-10000	0	0
mol:IP3	0	0.002	-10000	0	-0.004	101	101
cAMP biosynthetic process	0.002	0.055	-10000	0	-0.33	12	12
GNG2	0.009	0.053	-10000	0	-0.59	4	4
potassium channel inhibitor activity	0	0.002	-10000	0	-0.004	101	101
HRAS/GTP	-0.059	0.11	-10000	0	-0.29	79	79
actin cytoskeleton reorganization	-0.001	0.012	-10000	0	-0.28	1	1
SRC	0.014	0.001	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.002	-10000	0	-0.004	101	101
PI3K	0.001	0.017	-10000	0	-0.37	1	1
apoptosis	0.038	0.17	0.42	63	-10000	0	63
T-DHT/AR/PELP1	-0.07	0.14	-10000	0	-0.34	107	107
HRAS/GDP	-0.071	0.15	-10000	0	-0.43	72	72
CREB1	-0.042	0.18	-10000	0	-0.45	63	63
RAC1-CDC42/GTP	-0.001	0.013	-10000	0	-0.28	1	1
AR	-0.1	0.23	-10000	0	-0.56	107	107
GNB1	0.014	0	-10000	0	-10000	0	0
RAF1	-0.029	0.12	-10000	0	-0.34	24	24
RAC1-CDC42/GDP	-0.065	0.14	-10000	0	-0.4	72	72
T-DHT/AR/PELP1/Src	-0.062	0.13	-10000	0	-0.31	107	107
MAP2K2	-0.023	0.12	-10000	0	-0.34	24	24
T-DHT/AR/PELP1/Src/PI3K	-0.019	0.11	-10000	0	-0.26	72	72
GNAZ	0.014	0	-10000	0	-10000	0	0
SHBG	0	0.089	-10000	0	-0.58	12	12
Gi family/GNB1/GNG2/GDP	0.021	0.074	-10000	0	-0.45	6	6
mol:T-DHT	0	0.001	-10000	0	-0.003	73	73
RAC1	0.014	0	-10000	0	-10000	0	0
GNRH1	0.001	0.067	-10000	0	-0.4	14	14
Gi family/GTP	-0.013	0.08	-10000	0	-0.36	6	6
CDC42	0.014	0	-10000	0	-10000	0	0

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.063	0.15	0.4	81	-10000	0	81
KIRREL	-0.037	0.16	-10000	0	-0.59	41	41
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.063	0.15	-10000	0	-0.4	81	81
PLCG1	0.014	0	-10000	0	-10000	0	0
ARRB2	0.014	0	-10000	0	-10000	0	0
WASL	0.014	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.046	0.11	-10000	0	-0.34	42	42
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.004	0.096	-10000	0	-0.29	42	42
FYN	-0.024	0.11	-10000	0	-0.32	42	42
mol:Ca2+	-0.045	0.11	-10000	0	-0.33	42	42
mol:DAG	-0.045	0.11	-10000	0	-0.34	42	42
NPHS2	-0.006	0.039	-10000	0	-0.54	2	2
mol:IP3	-0.045	0.11	-10000	0	-0.34	42	42
regulation of endocytosis	-0.015	0.1	-10000	0	-0.3	42	42
Nephrin/NEPH1/podocin/Cholesterol	-0.047	0.11	-10000	0	-0.29	83	83
establishment of cell polarity	-0.063	0.15	-10000	0	-0.4	81	81
Nephrin/NEPH1/podocin/NCK1-2	-0.041	0.099	-10000	0	-0.31	38	38
Nephrin/NEPH1/beta Arrestin2	-0.014	0.1	-10000	0	-0.3	42	42
NPHS1	-0.035	0.14	-10000	0	-0.49	44	44
Nephrin/NEPH1/podocin	-0.027	0.11	-10000	0	-0.32	42	42
TJP1	0.014	0	-10000	0	-10000	0	0
NCK1	0.013	0.027	-10000	0	-0.59	1	1
NCK2	0.014	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.046	0.11	-10000	0	-0.34	42	42
CD2AP	0.014	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.046	0.11	-10000	0	-0.34	43	43
GRB2	0.013	0.022	-10000	0	-0.49	1	1
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.043	0.13	-10000	0	-0.31	79	79
cytoskeleton organization	-0.004	0.11	-10000	0	-0.33	42	42
Nephrin/NEPH1	-0.045	0.11	-10000	0	-0.28	81	81
Nephrin/NEPH1/ZO-1	-0.049	0.12	-10000	0	-0.31	81	81

×

EGFR-dependent Endothelin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.014	0	-9999	-10000	0	0
EGFR	-0.083	0.21	-9999	-0.55	89	89
EGF/EGFR	-0.11	0.17	-9999	-0.36	119	119
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.078	0.14	-9999	-0.53	17	17
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.021	0.14	-9999	-0.54	33	33
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.05	0.18	-9999	-0.56	58	58
EGF/EGFR dimer/SHC	-0.095	0.17	-9999	-0.4	91	91
mol:GDP	-0.077	0.14	-9999	-0.52	17	17
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.036	0.16	-9999	-0.52	48	48
GRB2/SOS1	-0.001	0.015	-9999	-0.34	1	1
HRAS/GTP	-0.07	0.13	-9999	-0.48	17	17
SHC1	0.009	0.049	-9999	-0.49	5	5
HRAS/GDP	-0.071	0.13	-9999	-0.49	17	17
FRAP1	-0.045	0.15	-9999	-0.5	17	17
EGF/EGFR dimer	-0.11	0.2	-9999	-0.43	132	132
SOS1	0.014	0	-9999	-10000	0	0
GRB2	0.013	0.022	-9999	-0.49	1	1
ETA receptor/Endothelin-1	-0.059	0.14	-9999	-0.39	78	78

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.059	0.12	-9999	-0.32	73	73
SMAD6-7/SMURF1	-0.004	0.036	-9999	-0.33	6	6
NOG	-0.064	0.2	-9999	-0.58	68	68
SMAD9	-0.029	0.16	-9999	-0.56	37	37
SMAD4	0.014	0	-9999	-10000	0	0
SMAD5	-0.001	0.12	-9999	-0.48	17	17
BMP7/USAG1	-0.092	0.16	-9999	-0.38	126	126
SMAD5/SKI	0.007	0.12	-9999	-0.46	16	16
SMAD1	0.044	0.029	-9999	-0.32	1	1
BMP2	-0.079	0.22	-9999	-0.59	79	79
SMAD1/SMAD1/SMAD4	-0.003	0.025	-9999	-10000	0	0
BMPR1A	0.014	0	-9999	-10000	0	0
BMPR1B	-0.022	0.14	-9999	-0.59	31	31
BMPR1A-1B/BAMBI	-0.027	0.1	-9999	-0.39	35	35
AHSG	-0.078	0.21	-9999	-0.55	83	83
CER1	-0.013	0.098	-9999	-0.49	21	21
BMP2-4/CER1	-0.082	0.19	-9999	-0.45	94	94
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.014	0.16	-9999	-0.46	40	40
BMP2-4 (homodimer)	-0.083	0.2	-9999	-0.51	84	84
RGMB	0.004	0.074	-9999	-0.55	9	9
BMP6/BMPR2/BMPR1A-1B	-0.028	0.092	-9999	-0.33	36	36
RGMA	-0.002	0.096	-9999	-0.58	14	14
SMURF1	0.014	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.021	0.15	-9999	-0.46	37	37
BMP2-4/USAG1	-0.14	0.22	-9999	-0.42	172	172
SMAD6/SMURF1/SMAD5	0.007	0.12	-9999	-0.46	16	16
SOSTDC1	-0.11	0.23	-9999	-0.52	120	120
BMP7/BMPR2/BMPR1A-1B	-0.023	0.083	-9999	-0.32	38	38
SKI	0.014	0	-9999	-10000	0	0
BMP6 (homodimer)	-0.004	0.097	-9999	-0.52	17	17
HFE2	0.002	0.066	-9999	-0.49	9	9
ZFYVE16	0.014	0	-9999	-10000	0	0
MAP3K7	0.014	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.075	0.17	-9999	-0.43	90	90
SMAD5/SMAD5/SMAD4	0.007	0.12	-9999	-0.45	17	17
MAPK1	0.014	0	-9999	-10000	0	0
TAK1/TAB family	-0.047	0.11	-9999	-0.4	34	34
BMP7 (homodimer)	0.006	0.07	-9999	-0.59	7	7
NUP214	0.014	0	-9999	-10000	0	0
BMP6/FETUA	-0.075	0.16	-9999	-0.41	95	95
SMAD1/SKI	0.05	0.028	-9999	-10000	0	0
SMAD6	0.008	0.062	-9999	-0.56	6	6
CTDSP2	0.01	0.044	-9999	-0.49	4	4
BMP2-4/FETUA	-0.12	0.21	-9999	-0.42	150	150
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.17	0.27	-9999	-0.55	168	168
BMPR2 (homodimer)	0.014	0	-9999	-10000	0	0
GADD34/PP1CA	-0.005	0.037	-9999	-0.28	9	9
BMPR1A-1B (homodimer)	-0.026	0.1	-9999	-0.43	31	31
CHRDL1	-0.077	0.21	-9999	-0.57	80	80
ENDOFIN/SMAD1	0.05	0.028	-9999	-0.3	1	1
SMAD6-7/SMURF1/SMAD1	-0.003	0.029	-9999	-10000	0	0
SMAD6/SMURF1	0.014	0	-9999	-10000	0	0
BAMBI	0.005	0.069	-9999	-0.51	9	9
SMURF2	0.012	0.038	-9999	-0.59	2	2
BMP2-4/CHRDL1	-0.12	0.21	-9999	-0.42	153	153
BMP2-4/GREM1	-0.18	0.23	-9999	-0.41	221	221
SMAD7	0.014	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.02	0.16	-9999	-0.52	37	37
SMAD1/SMAD6	0.05	0.028	-9999	-0.3	1	1
TAK1/SMAD6	0	0	-9999	-10000	0	0
BMP7	0.006	0.07	-9999	-0.59	7	7
BMP6	-0.004	0.097	-9999	-0.53	17	17
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.014	0.14	-9999	-0.42	37	37
PPM1A	0.014	0	-9999	-10000	0	0
SMAD1/SMURF2	0.049	0.035	-9999	-0.31	2	2
SMAD7/SMURF1	0	0	-9999	-10000	0	0
CTDSPL	0.013	0.027	-9999	-0.59	1	1
PPP1CA	0.014	0	-9999	-10000	0	0
XIAP	0.014	0	-9999	-10000	0	0
CTDSP1	0.014	0	-9999	-10000	0	0
PPP1R15A	0.005	0.066	-9999	-0.49	9	9
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.052	0.18	-9999	-0.48	54	54
CHRD	0.006	0.07	-9999	-0.59	7	7
BMPR2	0.014	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.03	0.16	-9999	-0.5	37	37
BMP4	-0.014	0.13	-9999	-0.58	24	24
FST	-0.067	0.2	-9999	-0.54	76	76
BMP2-4/NOG	-0.11	0.25	-9999	-0.54	109	109
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.021	0.076	-9999	-0.29	38	38

×

BCR signaling pathway

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
JUN	-0.037	0.14	-10000	0	-0.36	50	50
IKBKB	-0.012	0.078	-10000	0	-0.26	15	15
AKT1	-0.05	0.1	-10000	0	-0.25	48	48
IKBKG	-0.01	0.082	-10000	0	-0.27	21	21
CALM1	-0.055	0.15	-10000	0	-0.49	35	35
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
MAP3K1	-0.061	0.18	-10000	0	-0.49	54	54
MAP3K7	0.014	0	-10000	0	-10000	0	0
mol:Ca2+	-0.065	0.16	-10000	0	-0.44	57	57
DOK1	0.012	0.035	-10000	0	-0.54	2	2
AP-1	-0.034	0.099	0.18	2	-0.26	35	37
LYN	0.004	0.072	-10000	0	-0.51	10	10
BLNK	-0.056	0.19	-10000	0	-0.58	61	61
SHC1	0.009	0.049	-10000	0	-0.49	5	5
BCR complex	-0.076	0.18	-10000	0	-0.44	91	91
CD22	-0.17	0.21	-10000	0	-0.53	89	89
CAMK2G	-0.044	0.14	-10000	0	-0.48	30	30
CSNK2A1	0.014	0	-10000	0	-10000	0	0
INPP5D	0.008	0.06	-10000	0	-0.54	6	6
SHC/GRB2/SOS1	-0.091	0.17	-10000	0	-0.55	43	43
GO:0007205	-0.066	0.16	-10000	0	-0.44	57	57
SYK	-0.013	0.12	-10000	0	-0.57	24	24
ELK1	-0.055	0.15	-10000	0	-0.49	36	36
NFATC1	-0.061	0.17	-10000	0	-0.46	58	58
B-cell antigen/BCR complex	-0.076	0.18	-10000	0	-0.44	91	91
PAG1/CSK	-0.001	0.019	-10000	0	-0.43	1	1
NFKBIB	0.006	0.029	0.081	2	-10000	0	2
HRAS	-0.049	0.16	-10000	0	-0.48	38	38
NFKBIA	0.007	0.028	0.081	2	-10000	0	2
NF-kappa-B/RelA/I kappa B beta	0.013	0.023	-10000	0	-10000	0	0
RasGAP/Csk	-0.12	0.18	-10000	0	-0.55	51	51
mol:GDP	-0.062	0.16	-10000	0	-0.42	57	57
PTEN	0.013	0.027	-10000	0	-0.59	1	1
CD79B	-0.047	0.17	-10000	0	-0.53	58	58
NF-kappa-B/RelA/I kappa B alpha	0.013	0.023	-10000	0	-10000	0	0
GRB2	0.013	0.022	-10000	0	-0.49	1	1
PI3K/BCAP/CD19	-0.086	0.19	-10000	0	-0.51	63	63
PIK3R1	0.014	0	-10000	0	-10000	0	0
mol:IP3	-0.067	0.16	-10000	0	-0.45	57	57
CSK	0.014	0	-10000	0	-10000	0	0
FOS	-0.095	0.18	-10000	0	-0.53	48	48
CHUK	-0.01	0.082	-10000	0	-0.28	17	17
IBTK	0.014	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.064	0.14	-10000	0	-0.51	35	35
PTPN6	-0.16	0.21	-10000	0	-0.54	87	87
RELA	0.014	0	-10000	0	-10000	0	0
BCL2A1	-0.006	0.045	-10000	0	-0.099	44	44
VAV2	-0.11	0.18	-10000	0	-0.55	52	52
ubiquitin-dependent protein catabolic process	0.011	0.028	0.085	2	-10000	0	2
BTK	-0.041	0.2	-10000	0	-1.1	17	17
CD19	-0.11	0.18	-10000	0	-0.54	58	58
MAP4K1	-0.018	0.13	-10000	0	-0.58	28	28
CD72	-0.008	0.11	-10000	0	-0.51	22	22
PAG1	0.013	0.027	-10000	0	-0.59	1	1
MAPK14	-0.044	0.16	-10000	0	-0.43	48	48
SH3BP5	0.01	0.051	-10000	0	-0.57	4	4
PIK3AP1	-0.064	0.18	-10000	0	-0.5	56	56
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.065	0.22	-10000	0	-0.56	60	60
RAF1	-0.038	0.15	-10000	0	-0.48	31	31
RasGAP/p62DOK/SHIP	-0.12	0.18	-10000	0	-0.54	53	53
CD79A	-0.04	0.16	-10000	0	-0.54	50	50
re-entry into mitotic cell cycle	-0.034	0.099	0.18	2	-0.26	35	37
RASA1	0.014	0	-10000	0	-10000	0	0
MAPK3	-0.017	0.12	-10000	0	-0.41	25	25
MAPK1	-0.017	0.12	-10000	0	-0.41	25	25
CD72/SHP1	-0.14	0.22	-10000	0	-0.56	76	76
NFKB1	0.014	0	-10000	0	-10000	0	0
MAPK8	-0.051	0.16	-10000	0	-0.43	54	54
actin cytoskeleton organization	-0.062	0.17	-10000	0	-0.48	47	47
NF-kappa-B/RelA	0.03	0.045	-10000	0	-10000	0	0
Calcineurin	-0.057	0.12	-10000	0	-0.44	31	31
PI3K	-0.13	0.18	-10000	0	-0.48	73	73
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.081	0.17	0.24	2	-0.49	56	58
SOS1	0.014	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.11	0.27	-10000	0	-0.79	58	58
DAPP1	-0.14	0.29	-10000	0	-0.88	55	55
cytokine secretion	-0.056	0.16	-10000	0	-0.43	58	58
mol:DAG	-0.067	0.16	-10000	0	-0.45	57	57
PLCG2	0	0.088	-10000	0	-0.55	13	13
MAP2K1	-0.028	0.14	-10000	0	-0.45	27	27
B-cell antigen/BCR complex/FcgammaRIIB	-0.15	0.22	-10000	0	-0.47	132	132
mol:PI-3-4-5-P3	-0.1	0.12	-10000	0	-0.35	61	61
ETS1	-0.038	0.14	-10000	0	-0.43	33	33
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.1	0.2	-10000	0	-0.63	41	41
B-cell antigen/BCR complex/LYN	-0.1	0.18	-10000	0	-0.51	61	61
MALT1	0.014	0	-10000	0	-10000	0	0
TRAF6	0.013	0.027	-10000	0	-0.59	1	1
RAC1	-0.067	0.18	-10000	0	-0.52	47	47
B-cell antigen/BCR complex/LYN/SYK	-0.17	0.23	-10000	0	-0.61	78	78
CARD11	-0.066	0.18	-10000	0	-0.49	60	60
FCGR2B	-0.13	0.24	-10000	0	-0.53	138	138
PPP3CA	0.012	0.031	-10000	0	-0.49	2	2
BCL10	0.014	0	-10000	0	-10000	0	0
IKK complex	0.002	0.036	-10000	0	-0.12	1	1
PTPRC	-0.04	0.17	-10000	0	-0.54	51	51
PDPK1	-0.05	0.098	-10000	0	-0.25	50	50
PPP3CB	0.011	0.038	-10000	0	-0.49	3	3
PPP3CC	0.014	0	-10000	0	-10000	0	0
POU2F2	0.013	0.024	-10000	0	-0.099	7	7

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.036	0.23	-10000	0	-0.71	17	17
CRP	-0.043	0.23	-10000	0	-0.66	24	24
cell cycle arrest	-0.056	0.26	-10000	0	-0.68	41	41
TIMP1	-0.08	0.27	-10000	0	-0.67	46	46
IL6ST	-0.029	0.15	-10000	0	-0.59	36	36
Rac1/GDP	-0.068	0.2	-10000	0	-0.46	67	67
AP1	-0.018	0.14	-10000	0	-0.48	13	13
GAB2	0.014	0.027	-10000	0	-0.59	1	1
TNFSF11	-0.044	0.24	-10000	0	-0.73	17	17
HSP90B1	0.006	0.16	-10000	0	-0.92	13	13
GAB1	0.013	0.035	-10000	0	-0.54	2	2
MAPK14	-0.097	0.23	-10000	0	-0.5	95	95
AKT1	0.058	0.03	-10000	0	-0.45	1	1
FOXO1	0.063	0.036	-10000	0	-0.42	1	1
MAP2K6	-0.085	0.2	-10000	0	-0.48	71	71
mol:GTP	0	0.002	-10000	0	-10000	0	0
MAP2K4	-0.054	0.21	-10000	0	-0.48	61	61
MITF	-0.066	0.19	0.27	1	-0.42	73	74
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.014	0	-10000	0	-10000	0	0
A2M	0.018	0.071	-10000	0	-1.4	1	1
CEBPB	0.004	0.11	-10000	0	-0.57	17	17
GRB2/SOS1/GAB family/SHP2	0.004	0.078	-10000	0	-0.82	1	1
STAT3	-0.06	0.27	-10000	0	-0.72	41	41
STAT1	-0.008	0.035	-10000	0	-10000	0	0
CEBPD	-0.078	0.33	-10000	0	-0.93	48	48
PIK3CA	0.015	0.027	-10000	0	-0.59	1	1
PI3K	0.023	0.02	-10000	0	-0.43	1	1
JUN	0.003	0.074	-10000	0	-0.5	11	11
PIAS3/MITF	-0.056	0.18	-10000	0	-0.46	47	47
MAPK11	-0.1	0.24	-10000	0	-0.5	98	98
STAT3 (dimer)/FOXO1	0.015	0.21	-10000	0	-0.59	16	16
GRB2/SOS1/GAB family	-0.072	0.12	-10000	0	-0.46	30	30
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.065	0.17	-10000	0	-0.44	54	54
GRB2	0.014	0.022	-10000	0	-0.49	1	1
JAK2	0.014	0	-10000	0	-10000	0	0
LBP	-0.034	0.23	-10000	0	-0.64	31	31
PIK3R1	0.016	0	-10000	0	-10000	0	0
JAK1	0.012	0.009	-10000	0	-10000	0	0
MYC	-0.064	0.3	-10000	0	-0.95	35	35
FGG	-0.044	0.24	-10000	0	-0.64	30	30
macrophage differentiation	-0.056	0.26	-10000	0	-0.68	41	41
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.11	0.17	-10000	0	-0.43	69	69
JUNB	-0.056	0.27	-10000	0	-0.78	36	36
FOS	-0.096	0.22	-10000	0	-0.55	101	101
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.077	0.19	0.29	1	-0.43	81	82
STAT1/PIAS1	-0.054	0.18	0.29	1	-0.43	59	60
GRB2/SOS1/GAB family/SHP2/PI3K	0.045	0.032	-10000	0	-0.38	2	2
STAT3 (dimer)	-0.059	0.27	-10000	0	-0.71	41	41
PRKCD	-0.058	0.25	-10000	0	-0.61	53	53
IL6R	-0.014	0.12	-10000	0	-0.57	24	24
SOCS3	-0.15	0.34	-10000	0	-1	48	48
gp130 (dimer)/JAK1/JAK1/LMO4	0	0.1	-10000	0	-0.35	36	36
Rac1/GTP	-0.069	0.2	-10000	0	-0.46	71	71
HCK	-0.007	0.11	-10000	0	-0.54	20	20
MAPKKK cascade	0.025	0.068	-10000	0	-0.91	1	1
bone resorption	-0.04	0.23	-10000	0	-0.69	17	17
IRF1	-0.044	0.24	-10000	0	-0.72	21	21
mol:GDP	-0.079	0.2	0.28	1	-0.44	85	86
SOS1	0.015	0.002	-10000	0	-10000	0	0
VAV1	-0.081	0.2	0.28	1	-0.45	85	86
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.1	0.23	-10000	0	-0.46	112	112
PTPN11	-0.002	0.017	-10000	0	-10000	0	0
IL6/IL6RA	-0.1	0.2	-10000	0	-0.41	150	150
gp130 (dimer)/TYK2/TYK2/LMO4	-0.002	0.099	-10000	0	-0.35	36	36
gp130 (dimer)/JAK2/JAK2/LMO4	-0.002	0.099	-10000	0	-0.35	36	36
IL6	-0.13	0.24	-10000	0	-0.53	137	137
PIAS3	0.014	0	-10000	0	-10000	0	0
PTPRE	0.012	0.032	-10000	0	-0.6	1	1
PIAS1	0.009	0.053	-10000	0	-0.59	4	4
RAC1	0.015	0.001	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.067	0.16	0.26	1	-0.41	53	54
LMO4	0.014	0.012	-10000	0	-10000	0	0
STAT3 (dimer)/PIAS3	-0.12	0.21	0.35	1	-0.68	39	40
MCL1	0.064	0.027	-10000	0	-10000	0	0

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.085	0.28	-10000	0	-0.86	41	41
NCK1/PAK1/Dok-R	-0.095	0.13	-10000	0	-0.4	54	54
NCK1/Dok-R	-0.11	0.32	-10000	0	-1.1	40	40
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
mol:beta2-estradiol	0.015	0.064	0.22	30	-10000	0	30
RELA	0.014	0	-10000	0	-10000	0	0
SHC1	0.009	0.049	-10000	0	-0.49	5	5
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	0.013	0.089	0.25	17	-0.47	8	25
TNIP2	0.014	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.11	0.26	-10000	0	-1	37	37
FN1	-0.003	0.092	-10000	0	-0.49	18	18
PLD2	-0.084	0.31	-10000	0	-1.1	37	37
PTPN11	0.014	0	-10000	0	-10000	0	0
GRB14	-0.18	0.26	-10000	0	-0.53	186	186
ELK1	-0.061	0.28	-10000	0	-0.99	37	37
GRB7	-0.032	0.14	-10000	0	-0.49	43	43
PAK1	-0.035	0.15	-10000	0	-0.5	49	49
Tie2/Ang1/alpha5/beta1 Integrin	-0.13	0.29	-10000	0	-1	42	42
CDKN1A	-0.1	0.28	-10000	0	-0.68	73	73
ITGA5	-0.01	0.11	-10000	0	-0.5	24	24
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.11	0.32	-10000	0	-1.1	39	39
CRK	0.014	0	-10000	0	-10000	0	0
mol:NO	-0.057	0.22	-10000	0	-0.63	43	43
PLG	-0.093	0.31	-10000	0	-1.1	38	38
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.077	0.26	-10000	0	-0.84	39	39
GRB2	0.013	0.022	-10000	0	-0.49	1	1
PIK3R1	0.014	0.002	-10000	0	-10000	0	0
ANGPT2	-0.11	0.28	-10000	0	-0.86	44	44
BMX	-0.11	0.32	-10000	0	-1.1	40	40
ANGPT1	-0.13	0.34	-10000	0	-1	50	50
tube development	-0.083	0.26	-10000	0	-0.66	61	61
ANGPT4	-0.05	0.18	-10000	0	-0.54	58	58
response to hypoxia	-0.008	0.021	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.18	0.36	-10000	0	-1.1	48	48
alpha5/beta1 Integrin	-0.017	0.079	-10000	0	-0.36	25	25
FGF2	0.011	0.044	-10000	0	-0.56	3	3
STAT5A (dimer)	-0.11	0.31	-10000	0	-0.76	69	69
mol:L-citrulline	-0.057	0.22	-10000	0	-0.63	43	43
AGTR1	-0.034	0.16	-10000	0	-0.55	43	43
MAPK14	-0.089	0.31	-10000	0	-1.1	37	37
Tie2/SHP2	-0.041	0.16	-10000	0	-1.2	8	8
TEK	-0.023	0.19	-10000	0	-1.3	8	8
RPS6KB1	-0.072	0.26	-10000	0	-0.84	38	38
Angiotensin II/AT1	-0.025	0.12	-10000	0	-0.4	43	43
Tie2/Ang1/GRB2	-0.087	0.32	-10000	0	-1.2	37	37
MAPK3	-0.068	0.29	-10000	0	-1	37	37
MAPK1	-0.068	0.29	-10000	0	-1	37	37
Tie2/Ang1/GRB7	-0.11	0.33	-10000	0	-1.1	40	40
NFKB1	0.014	0	-10000	0	-10000	0	0
MAPK8	-0.091	0.32	-10000	0	-1.1	38	38
PI3K	-0.094	0.31	-10000	0	-1	38	38
FES	-0.089	0.31	-10000	0	-1.1	37	37
Crk/Dok-R	-0.11	0.32	-10000	0	-1.1	40	40
Tie2/Ang1/ABIN2	-0.087	0.32	-10000	0	-1.2	37	37
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.075	0.26	-10000	0	-0.76	42	42
STAT5A	0.001	0.088	-10000	0	-0.59	11	11
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.072	0.26	-10000	0	-0.84	38	38
Tie2/Ang2	-0.12	0.34	-10000	0	-0.93	57	57
Tie2/Ang1	-0.099	0.34	-10000	0	-1.2	37	37
FOXO1	-0.082	0.27	-10000	0	-0.73	56	56
ELF1	0.019	0.032	-10000	0	-0.64	1	1
ELF2	-0.088	0.31	-10000	0	-1.1	37	37
mol:Choline	-0.078	0.3	-10000	0	-1.1	37	37
cell migration	-0.054	0.073	-10000	0	-0.23	45	45
FYN	-0.097	0.29	-10000	0	-0.76	57	57
DOK2	-0.07	0.2	-10000	0	-0.53	80	80
negative regulation of cell cycle	-0.088	0.26	-10000	0	-0.61	75	75
ETS1	-0.011	0.1	-10000	0	-0.56	12	12
PXN	-0.05	0.23	-10000	0	-0.69	38	38
ITGB1	0.012	0.031	-10000	0	-0.49	2	2
NOS3	-0.068	0.25	-10000	0	-0.72	42	42
RAC1	0.014	0	-10000	0	-10000	0	0
TNF	-0.17	0.27	-10000	0	-0.56	156	156
MAPKKK cascade	-0.078	0.3	-10000	0	-1.1	37	37
RASA1	0.014	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.091	0.33	-10000	0	-1.2	37	37
NCK1	0.013	0.027	-10000	0	-0.59	1	1
vasculogenesis	-0.049	0.2	-10000	0	-0.56	43	43
mol:Phosphatidic acid	-0.078	0.3	-10000	0	-1.1	37	37
mol:Angiotensin II	-0.001	0.008	-10000	0	-10000	0	0
mol:NADP	-0.057	0.22	-10000	0	-0.63	43	43
Rac1/GTP	-0.12	0.22	-10000	0	-0.77	39	39
MMP2	-0.097	0.32	-10000	0	-1.1	39	39

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.03	0.14	-9999	-0.38	58	58
CRKL	0.013	0.022	-9999	-0.49	1	1
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0.009	0.053	-9999	-0.59	4	4
ITGA4	-0.052	0.18	-9999	-0.53	62	62
alpha4/beta7 Integrin/MAdCAM1	-0.12	0.18	-9999	-0.4	99	99
EPO	-0.007	0.098	-9999	-0.5	20	20
alpha4/beta7 Integrin	-0.077	0.17	-9999	-0.43	93	93
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.014	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.047	0.13	-9999	-0.39	62	62
EPO/EPOR (dimer)	-0.014	0.071	-9999	-0.36	20	20
lamellipodium assembly	0.009	0.022	-9999	-0.29	1	1
PIK3CA	0.013	0.027	-9999	-0.59	1	1
PI3K	-0.001	0.019	-9999	-0.43	1	1
ARF6	0.014	0	-9999	-10000	0	0
JAK2	0	0.09	-9999	-0.29	11	11
PXN	0.014	0	-9999	-10000	0	0
PIK3R1	0.014	0	-9999	-10000	0	0
MADCAM1	-0.11	0.23	-9999	-0.53	120	120
cell adhesion	-0.12	0.17	-9999	-0.4	99	99
CRKL/CBL	-0.001	0.015	-9999	-0.34	1	1
ITGB1	0.012	0.031	-9999	-0.49	2	2
SRC	-0.087	0.18	-9999	-0.35	124	124
ITGB7	-0.034	0.16	-9999	-0.54	45	45
RAC1	0.014	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.12	0.18	-9999	-0.35	182	182
p130Cas/Crk/Dock1	-0.054	0.16	-9999	-0.5	17	17
VCAM1	-0.14	0.25	-9999	-0.56	134	134
RHOA	0.014	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.034	0.094	-9999	-0.33	28	28
BCAR1	-0.073	0.17	-9999	-0.55	15	15
EPOR	0.013	0.022	-9999	-0.49	1	1
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.014	0	-9999	-10000	0	0
GIT1	0.014	0	-9999	-10000	0	0
Rac1/GTP	0.009	0.022	-9999	-0.3	1	1

×

Retinoic acid receptors-mediated signaling

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
HDAC1	0.009	0.053	-10000	0	-0.59	4	4
HDAC3	0.014	0	-10000	0	-10000	0	0
VDR	-0.065	0.19	-10000	0	-0.53	74	74
Cbp/p300/PCAF	-0.003	0.034	-10000	0	-0.34	5	5
EP300	0.009	0.053	-10000	0	-0.59	4	4
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.015	0.064	-10000	0	-0.4	5	5
KAT2B	0.013	0.022	-10000	0	-0.49	1	1
MAPK14	0.014	0	-10000	0	-10000	0	0
AKT1	0.008	0.07	0.22	7	-0.34	3	10
RAR alpha/9cRA/Cyclin H	-0.053	0.087	-10000	0	-0.74	2	2
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.013	0.058	-10000	0	-0.34	5	5
CDC2	0.001	0	-10000	0	-10000	0	0
response to UV	0.001	0	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.065	0.11	-10000	0	-0.53	14	14
NCOR2	0.014	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	-0.056	0.14	-10000	0	-0.39	74	74
RXRs/RARs/NRIP1/9cRA	-0.061	0.2	-10000	0	-0.45	90	90
NCOA2	-0.027	0.15	-10000	0	-0.59	35	35
NCOA3	0.014	0	-10000	0	-10000	0	0
NCOA1	0.014	0	-10000	0	-10000	0	0
VDR/VDR/DNA	-0.064	0.19	-10000	0	-0.53	74	74
RARG	0.014	0.022	-10000	0	-0.49	1	1
RAR gamma1/9cRA	-0.001	0.013	-10000	0	-0.29	1	1
MAPK3	0.015	0	-10000	0	-10000	0	0
MAPK1	0.014	0	-10000	0	-10000	0	0
MAPK8	-0.001	0.099	-10000	0	-0.59	14	14
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.15	0.22	-10000	0	-0.55	96	96
RARA	-0.053	0.12	-10000	0	-0.26	102	102
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.005	0.097	-10000	0	-0.37	18	18
PRKCA	0.016	0.027	-10000	0	-0.59	1	1
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.074	0.2	-10000	0	-0.46	90	90
RXRG	-0.13	0.22	-10000	0	-0.44	124	124
RXRA	-0.037	0.11	-10000	0	-0.7	2	2
RXRB	-0.076	0.15	-10000	0	-0.35	90	90
VDR/Vit D3/DNA	-0.056	0.14	-10000	0	-0.39	74	74
RBP1	-0.075	0.2	-10000	0	-0.5	89	89
CRBP1/9-cic-RA	-0.062	0.14	-10000	0	-0.36	89	89
RARB	0.013	0.046	-10000	0	-0.59	3	3
PRKCG	-0.19	0.27	-10000	0	-0.54	193	193
MNAT1	0.013	0.022	-10000	0	-0.49	1	1
RAR alpha/RXRs	-0.064	0.21	-10000	0	-0.47	90	90
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.049	0.17	-10000	0	-0.38	90	90
proteasomal ubiquitin-dependent protein catabolic process	-0.008	0.097	-10000	0	-0.41	7	7
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.074	0.2	-10000	0	-0.46	90	90
positive regulation of DNA binding	-0.051	0.082	-10000	0	-0.67	2	2
NRIP1	-0.065	0.18	-10000	0	-0.58	27	27
RXRs/RARs	-0.081	0.2	-10000	0	-0.46	92	92
RXRs/RXRs/DNA/9cRA	-0.12	0.2	-10000	0	-0.52	90	90
PRKACA	0.014	0	-10000	0	-10000	0	0
CDK7	0.014	0	-10000	0	-10000	0	0
TFIIH	-0.001	0.012	-10000	0	-0.28	1	1
RAR alpha/9cRA	-0.038	0.065	-10000	0	-0.6	2	2
CCNH	0.014	0	-10000	0	-10000	0	0
CREBBP	0.014	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	-0.001	0.012	-10000	0	-10000	0	0

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.013	0.022	-9999	-0.49	1	1
LAT2	-0.052	0.18	-9999	-0.6	32	32
AP1	-0.11	0.18	-9999	-0.54	54	54
mol:PIP3	-0.063	0.2	-9999	-0.58	39	39
IKBKB	-0.029	0.11	-9999	-0.3	31	31
AKT1	-0.034	0.14	-9999	-0.42	23	23
IKBKG	-0.029	0.11	-9999	-0.28	36	36
MS4A2	-0.022	0.11	-9999	-0.49	25	25
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.013	0.027	-9999	-0.59	1	1
MAP3K1	-0.018	0.15	-9999	-0.52	31	31
mol:Ca2+	-0.043	0.15	-9999	-0.41	39	39
LYN	0.003	0.074	-9999	-0.52	10	10
CBLB	-0.039	0.14	-9999	-0.5	24	24
SHC1	0.009	0.049	-9999	-0.49	5	5
RasGAP/p62DOK	-0.019	0.071	-9999	-0.33	14	14
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0.008	0.06	-9999	-0.54	6	6
PLD2	-0.07	0.16	-9999	-0.36	73	73
PTPN13	-0.03	0.14	-9999	-0.56	20	20
PTPN11	0.011	0.009	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.003	0.12	-9999	-0.34	20	20
SYK	-0.014	0.13	-9999	-0.58	24	24
GRB2	0.013	0.022	-9999	-0.49	1	1
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.11	0.17	-9999	-0.59	39	39
LAT	-0.054	0.15	-9999	-0.42	48	48
PAK2	-0.027	0.17	-9999	-0.61	30	30
NFATC2	-0.099	0.19	-9999	-0.5	72	72
HRAS	-0.04	0.19	-9999	-0.67	32	32
GAB2	0.013	0.027	-9999	-0.59	1	1
PLA2G1B	0.039	0.024	-9999	-10000	0	0
Fc epsilon R1	-0.12	0.18	-9999	-0.36	178	178
Antigen/IgE/Fc epsilon R1	-0.11	0.17	-9999	-0.35	146	146
mol:GDP	-0.049	0.2	-9999	-0.7	34	34
JUN	0.003	0.074	-9999	-0.5	11	11
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.014	0.001	-9999	-10000	0	0
FOS	-0.096	0.22	-9999	-0.55	101	101
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.064	0.14	-9999	-0.49	29	29
CHUK	-0.029	0.11	-9999	-0.3	31	31
KLRG1	-0.042	0.14	-9999	-0.5	24	24
VAV1	-0.054	0.18	-9999	-0.62	34	34
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.037	0.14	-9999	-0.52	22	22
negative regulation of mast cell degranulation	-0.035	0.14	-9999	-0.52	24	24
BTK	-0.072	0.2	-9999	-0.75	30	30
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.11	0.19	-9999	-0.4	94	94
GAB2/PI3K/SHP2	-0.081	0.13	-9999	-0.46	23	23
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.056	0.16	-9999	-0.49	33	33
RAF1	0.029	0.025	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.17	0.22	-9999	-0.44	157	157
FCER1G	-0.02	0.14	-9999	-0.57	30	30
FCER1A	-0.14	0.25	-9999	-0.54	148	148
Antigen/IgE/Fc epsilon R1/Fyn	-0.1	0.16	-9999	-0.36	93	93
MAPK3	0.038	0.023	-9999	-10000	0	0
MAPK1	0.038	0.023	-9999	-10000	0	0
NFKB1	0.014	0	-9999	-10000	0	0
MAPK8	-0.004	0.11	-9999	-0.59	14	14
DUSP1	-0.02	0.13	-9999	-0.53	32	32
NF-kappa-B/RelA	-0.033	0.049	-9999	-0.23	1	1
actin cytoskeleton reorganization	-0.035	0.13	-9999	-0.53	20	20
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.069	0.16	-9999	-0.63	30	30
FER	-0.051	0.15	-9999	-0.45	43	43
RELA	0.014	0	-9999	-10000	0	0
ITK	-0.067	0.12	-9999	-0.3	79	79
SOS1	0.014	0	-9999	-10000	0	0
PLCG1	-0.047	0.21	-9999	-0.7	34	34
cytokine secretion	-0.024	0.036	-9999	-10000	0	0
SPHK1	-0.059	0.16	-9999	-0.48	41	41
PTK2	-0.037	0.14	-9999	-0.56	20	20
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.1	0.19	-9999	-0.68	34	34
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.051	0.19	-9999	-0.59	32	32
MAP2K2	0.035	0.022	-9999	-10000	0	0
MAP2K1	0.033	0.028	-9999	-10000	0	0
MAP2K7	0.014	0	-9999	-10000	0	0
KLRG1/SHP2	-0.047	0.13	-9999	-0.48	23	23
MAP2K4	0.02	0.014	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.19	0.22	-9999	-0.46	161	161
mol:Choline	-0.069	0.16	-9999	-0.34	86	86
SHC/Grb2/SOS1	-0.059	0.11	-9999	-0.5	22	22
FYN	0.014	0	-9999	-10000	0	0
DOK1	0.012	0.035	-9999	-0.54	2	2
PXN	-0.026	0.13	-9999	-0.51	20	20
HCLS1	-0.055	0.17	-9999	-0.56	37	37
PRKCB	-0.052	0.14	-9999	-0.38	50	50
FCGR2B	-0.13	0.24	-9999	-0.53	138	138
IGHE	-0.001	0.006	-9999	-10000	0	0
KLRG1/SHIP	-0.035	0.14	-9999	-0.53	24	24
LCP2	-0.001	0.086	-9999	-0.5	15	15
PLA2G4A	-0.054	0.16	-9999	-0.45	47	47
RASA1	0.014	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.069	0.16	-9999	-0.34	86	86
IKK complex	-0.008	0.086	-9999	-0.22	21	21
WIPF1	0.014	0	-9999	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.002	0.17	-9999	-1.3	9	9
VDR	-0.065	0.19	-9999	-0.53	74	74
FAM120B	0.014	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.048	0.16	-9999	-0.45	31	31
RXRs/LXRs/DNA/Oxysterols	-0.075	0.22	-9999	-0.45	97	97
MED1	0.014	0	-9999	-10000	0	0
mol:9cRA	-0.009	0.024	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	0.027	0.056	-9999	-10000	0	0
RXRs/NUR77	-0.035	0.14	-9999	-0.35	73	73
RXRs/PPAR	-0.017	0.12	-9999	-0.36	32	32
NCOR2	0.014	0	-9999	-10000	0	0
VDR/VDR/Vit D3	-0.056	0.14	-9999	-0.39	74	74
RARs/VDR/DNA/Vit D3	-0.039	0.097	-9999	-0.31	35	35
RARA	0.014	0	-9999	-10000	0	0
NCOA1	0.014	0	-9999	-10000	0	0
VDR/VDR/DNA	-0.064	0.19	-9999	-0.53	74	74
RARs/RARs/DNA/9cRA	0.017	0.032	-9999	-0.3	4	4
RARG	0.013	0.022	-9999	-0.49	1	1
RPS6KB1	0.02	0.067	-9999	-0.4	9	9
RARs/THRs/DNA/SMRT	0.027	0.056	-9999	-10000	0	0
THRA	0.011	0.046	-9999	-0.59	3	3
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	-0.056	0.14	-9999	-0.39	74	74
RXRs/PPAR/9cRA/PGJ2/DNA	-0.036	0.13	-9999	-0.35	60	60
NR1H4	-0.12	0.24	-9999	-0.53	129	129
RXRs/LXRs/DNA	-0.024	0.14	-9999	-0.43	23	23
NR1H2	0.011	0.017	-9999	-10000	0	0
NR1H3	0.009	0.02	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.058	0.16	-9999	-0.36	97	97
NR4A1	-0.017	0.13	-9999	-0.51	31	31
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.066	0.14	-9999	-0.32	84	84
RXRG	-0.065	0.2	-9999	-0.59	65	65
RXR alpha/CCPG	0.017	0.013	-9999	-10000	0	0
RXRA	0.011	0.017	-9999	-10000	0	0
RXRB	0.009	0.02	-9999	-10000	0	0
THRB	-0.012	0.12	-9999	-0.53	25	25
PPARG	-0.014	0.12	-9999	-0.56	25	25
PPARD	0.014	0	-9999	-10000	0	0
TNF	-0.19	0.42	-9999	-1	84	84
mol:Oxysterols	-0.007	0.022	-9999	-10000	0	0
cholesterol transport	-0.074	0.21	-9999	-0.44	97	97
PPARA	0.014	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	0.011	0.046	-9999	-0.59	3	3
RXRs/NUR77/BCL2	-0.024	0.12	-9999	-0.31	68	68
SREBF1	-0.079	0.26	-9999	-0.88	31	31
RXRs/RXRs/DNA/9cRA	-0.036	0.13	-9999	-0.35	63	63
ABCA1	-0.079	0.26	-9999	-0.87	32	32
RARs/THRs	-0.016	0.062	-9999	-10000	0	0
RXRs/FXR	-0.093	0.19	-9999	-0.38	122	122
BCL2	0.005	0.075	-9999	-0.59	8	8

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.039	0.11	-10000	0	-0.32	64	64
MAPK9	0.009	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.13	0.19	-10000	0	-0.39	175	175
GNB1/GNG2	-0.003	0.032	-10000	0	-0.37	4	4
GNB1	0.014	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.009	0	-10000	0	-10000	0	0
Gs family/GTP	-0.041	0.11	-10000	0	-0.34	62	62
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	0.01	0.028	0.087	62	-10000	0	62
GNAL	-0.058	0.2	-10000	0	-0.59	62	62
GNG2	0.009	0.053	-10000	0	-0.59	4	4
CRH	-0.18	0.26	-10000	0	-0.54	175	175
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	-0.001	0.061	-10000	0	-0.36	14	14
MAPK11	0.003	0.049	-10000	0	-0.36	9	9

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.013	0.004	-9999	-10000	0	0
SVIL	-0.011	0.11	-9999	-0.5	24	24
ZNF318	0.019	0.018	-9999	-10000	0	0
JMJD2C	-0.003	0.021	-9999	-0.076	36	36
T-DHT/AR/Ubc9	-0.068	0.16	-9999	-0.36	107	107
CARM1	0.014	0.001	-9999	-10000	0	0
PRDX1	-0.014	0.13	-9999	-0.59	24	24
PELP1	0.015	0.003	-9999	-10000	0	0
CTNNB1	0.013	0.004	-9999	-10000	0	0
AKT1	0.015	0.005	-9999	-10000	0	0
PTK2B	-0.01	0.11	-9999	-0.49	24	24
MED1	0.015	0.005	-9999	-10000	0	0
MAK	-0.034	0.16	-9999	-0.5	53	53
response to oxidative stress	0	0.001	-9999	-10000	0	0
HIP1	-0.002	0.096	-9999	-0.6	13	13
GSN	0	0.089	-9999	-0.58	12	12
NCOA2	-0.027	0.15	-9999	-0.59	35	35
NCOA6	0.013	0.004	-9999	-10000	0	0
DNA-PK	0.008	0.025	-9999	-10000	0	0
NCOA4	0.014	0.001	-9999	-10000	0	0
PIAS3	0.013	0.004	-9999	-10000	0	0
cell proliferation	-0.042	0.11	-9999	-0.37	28	28
XRCC5	0.015	0.004	-9999	-10000	0	0
UBE3A	0.012	0.009	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.081	0.18	-9999	-0.38	120	120
FHL2	-0.048	0.21	-9999	-0.62	45	45
RANBP9	0.013	0.004	-9999	-10000	0	0
JMJD1A	-0.009	0.053	-9999	-0.11	97	97
CDK6	-0.033	0.16	-9999	-0.54	44	44
TGFB1I1	0.003	0.075	-9999	-0.53	10	10
T-DHT/AR/CyclinD1	-0.087	0.18	-9999	-0.39	125	125
XRCC6	0.015	0.004	-9999	-10000	0	0
T-DHT/AR	-0.076	0.18	-9999	-0.38	116	116
CTDSP1	0.013	0.004	-9999	-10000	0	0
CTDSP2	0.013	0.046	-9999	-0.49	4	4
BRCA1	0.009	0.044	-9999	-0.49	4	4
TCF4	0.015	0.028	-9999	-0.59	1	1
CDKN2A	-0.1	0.23	-9999	-0.56	104	104
SRF	0.016	0.028	-9999	-10000	0	0
NKX3-1	-0.059	0.18	-9999	-0.99	13	13
KLK3	-0.018	0.11	-9999	-10000	0	0
TMF1	0.012	0.027	-9999	-0.59	1	1
HNRNPA1	0.016	0.006	-9999	-10000	0	0
AOF2	-0.002	0.008	-9999	-10000	0	0
APPL1	0.027	0.01	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.076	0.17	-9999	-0.37	119	119
AR	-0.12	0.24	-9999	-0.57	107	107
UBA3	0.013	0.004	-9999	-10000	0	0
PATZ1	0.016	0.006	-9999	-10000	0	0
PAWR	-0.034	0.15	-9999	-0.53	45	45
PRKDC	0.015	0.004	-9999	-10000	0	0
PA2G4	0.016	0.007	-9999	-10000	0	0
UBE2I	0.014	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.061	0.15	-9999	-0.33	108	108
RPS6KA3	0.012	0.027	-9999	-0.59	1	1
T-DHT/AR/ARA70	-0.068	0.16	-9999	-0.36	107	107
LATS2	-0.001	0.094	-9999	-0.52	16	16
T-DHT/AR/PRX1	-0.075	0.17	-9999	-0.36	119	119
Cyclin D3/CDK11 p58	0	0.016	-9999	-0.35	1	1
VAV3	-0.12	0.23	-9999	-0.52	127	127
KLK2	-0.065	0.12	-9999	-0.44	36	36
CASP8	-0.001	0.089	-9999	-0.5	16	16
T-DHT/AR/TIF2/CARM1	-0.076	0.18	-9999	-0.38	108	108
TMPRSS2	-0.14	0.31	-9999	-0.88	62	62
CCND1	-0.017	0.13	-9999	-0.53	29	29
PIAS1	0.007	0.054	-9999	-0.59	4	4
mol:T-DHT	-0.011	0.031	-9999	-0.081	52	52
CDC2L1	0	0.001	-9999	-10000	0	0
PIAS4	0.01	0.015	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.096	0.19	-9999	-0.38	139	139
CMTM2	-0.007	0.11	-9999	-0.56	19	19
SNURF	-0.008	0.11	-9999	-0.58	19	19
ZMIZ1	0.006	0.026	-9999	-10000	0	0
CCND3	0.013	0.022	-9999	-0.49	1	1
TGIF1	-0.007	0.11	-9999	-0.53	21	21
FKBP4	0.013	0.004	-9999	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.072	0.15	-9999	-0.37	80	80
MAP4K1	-0.018	0.13	-9999	-0.58	28	28
MAP3K8	-0.005	0.099	-9999	-0.51	19	19
PRKCB	-0.062	0.19	-9999	-0.52	73	73
DBNL	0.014	0	-9999	-10000	0	0
CRKL	0.013	0.022	-9999	-0.49	1	1
MAP3K1	-0.004	0.11	-9999	-0.43	8	8
JUN	-0.03	0.16	-9999	-0.56	37	37
MAP3K7	-0.001	0.1	-9999	-0.44	7	7
GRAP2	-0.048	0.17	-9999	-0.53	58	58
CRK	0.014	0	-9999	-10000	0	0
MAP2K4	0.003	0.11	-9999	-0.4	12	12
LAT	-0.017	0.13	-9999	-0.59	27	27
LCP2	-0.001	0.086	-9999	-0.5	15	15
MAPK8	-0.034	0.16	-9999	-0.59	36	36
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.01	0.11	-9999	-0.29	36	36
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.066	0.14	-9999	-0.34	80	80

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.013	0.022	-10000	0	-0.49	1	1
RAS family/GTP/Tiam1	0.029	0.038	-10000	0	-0.51	1	1
NT3 (dimer)/TRKC	-0.015	0.078	-10000	0	-0.39	20	20
NT3 (dimer)/TRKB	-0.074	0.15	-10000	0	-0.36	104	104
SHC/Grb2/SOS1/GAB1/PI3K	0.037	0.03	-10000	0	-0.45	1	1
RAPGEF1	0.014	0	-10000	0	-10000	0	0
BDNF	-0.08	0.2	-10000	0	-0.51	93	93
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
DYNLT1	0.012	0.038	-10000	0	-0.59	2	2
NTRK1	-0.008	0.11	-10000	0	-0.52	22	22
NTRK2	-0.018	0.14	-10000	0	-0.59	27	27
NTRK3	0.009	0.053	-10000	0	-0.59	4	4
NT-4/5 (dimer)/TRKB	-0.073	0.16	-10000	0	-0.37	102	102
neuron apoptosis	0.13	0.16	0.4	101	-10000	0	101
SHC 2-3/Grb2	-0.12	0.2	-10000	0	-0.44	101	101
SHC1	0.009	0.049	-10000	0	-0.49	5	5
SHC2	-0.07	0.11	-10000	0	-0.39	34	34
SHC3	-0.16	0.23	-10000	0	-0.54	112	112
STAT3 (dimer)	0.007	0.067	-10000	0	-0.34	11	11
NT3 (dimer)/TRKA	-0.068	0.14	-10000	0	-0.34	102	102
RIN/GDP	-0.039	0.11	-10000	0	-0.26	18	18
GIPC1	0.013	0.022	-10000	0	-0.49	1	1
KRAS	0.013	0.022	-10000	0	-0.49	1	1
DNAJA3	-0.069	0.12	-10000	0	-0.38	46	46
RIN/GTP	-0.16	0.2	-10000	0	-0.4	206	206
CCND1	0	0.15	-10000	0	-0.57	29	29
MAGED1	0.014	0	-10000	0	-10000	0	0
PTPN11	0.014	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.011	0.09	-10000	0	-0.5	17	17
SHC/GRB2/SOS1	-0.003	0.03	-10000	0	-0.28	6	6
GRB2	0.013	0.022	-10000	0	-0.49	1	1
NGF (dimer)/TRKA/MATK	-0.12	0.19	-10000	0	-0.38	167	167
TRKA/NEDD4-2	-0.026	0.097	-10000	0	-0.38	35	35
ELMO1	0.001	0.088	-10000	0	-0.59	11	11
RhoG/GTP/ELMO1/DOCK1	-0.011	0.062	-10000	0	-0.37	15	15
NGF	-0.071	0.2	-10000	0	-0.56	77	77
HRAS	0.014	0	-10000	0	-10000	0	0
DOCK1	0.009	0.053	-10000	0	-0.59	4	4
GAB2	0.013	0.027	-10000	0	-0.59	1	1
RIT2	-0.21	0.28	-10000	0	-0.55	206	206
RIT1	0.014	0	-10000	0	-10000	0	0
FRS2	0.012	0.035	-10000	0	-0.54	2	2
DNM1	-0.1	0.22	-10000	0	-0.52	112	112
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.014	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.073	0.13	-10000	0	-0.37	57	57
mol:GDP	0.045	0.066	-10000	0	-0.46	2	2
NGF (dimer)	-0.071	0.2	-10000	0	-0.56	77	77
RhoG/GDP	-0.009	0.063	-10000	0	-0.44	11	11
RIT1/GDP	0.041	0.048	-10000	0	-0.29	2	2
TIAM1	0.013	0.027	-10000	0	-0.59	1	1
PIK3R1	0.014	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.075	0.14	-10000	0	-0.32	121	121
KIDINS220/CRKL/C3G	-0.001	0.015	-10000	0	-0.34	1	1
SHC/RasGAP	-0.003	0.033	-10000	0	-0.34	5	5
FRS2 family/SHP2	-0.001	0.02	-10000	0	-0.32	2	2
SHC/GRB2/SOS1/GAB1	-0.004	0.036	-10000	0	-0.57	1	1
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.008	0.092	-10000	0	-0.49	18	18
RAP1/GDP	-0.005	0.022	-10000	0	-0.24	2	2
KIDINS220/CRKL	0.013	0.022	-10000	0	-0.49	1	1
BDNF (dimer)	-0.079	0.2	-10000	0	-0.5	93	93
ubiquitin-dependent protein catabolic process	-0.07	0.14	-10000	0	-0.35	104	104
Schwann cell development	-0.02	0.027	-10000	0	-10000	0	0
EHD4	0.007	0.058	-10000	0	-0.49	7	7
FRS2 family/GRB2/SOS1	-0.002	0.021	-10000	0	-0.32	1	1
FRS2 family/SHP2/CRK family/C3G/GAB2	0.043	0.018	-10000	0	-10000	0	0
RAP1B	0.013	0.022	-10000	0	-0.49	1	1
RAP1A	0.014	0	-10000	0	-10000	0	0
CDC42/GTP	-0.061	0.12	-10000	0	-0.48	18	18
ABL1	0.014	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	-0.001	0.015	-10000	0	-0.34	1	1
Rap1/GTP	-0.022	0.044	-10000	0	-10000	0	0
STAT3	0.007	0.067	-10000	0	-0.34	11	11
axon guidance	-0.059	0.11	-10000	0	-0.46	18	18
MAPK3	-0.085	0.19	-10000	0	-0.39	107	107
MAPK1	-0.085	0.19	-10000	0	-0.39	107	107
CDC42/GDP	0.041	0.048	-10000	0	-0.29	2	2
NTF3	-0.008	0.092	-10000	0	-0.49	18	18
NTF4	-0.011	0.09	-10000	0	-0.5	17	17
NGF (dimer)/TRKA/FAIM	-0.065	0.14	-10000	0	-0.34	98	98
PI3K	-0.001	0.019	-10000	0	-0.43	1	1
FRS3	0.014	0	-10000	0	-10000	0	0
FAIM	0.009	0.053	-10000	0	-0.59	4	4
GAB1	0.012	0.035	-10000	0	-0.54	2	2
RASGRF1	-0.12	0.17	-10000	0	-0.38	108	108
SOS1	0.014	0	-10000	0	-10000	0	0
MCF2L	0.013	0.072	-10000	0	-0.32	21	21
RGS19	0.014	0	-10000	0	-10000	0	0
CDC42	0.014	0	-10000	0	-10000	0	0
RAS family/GTP	0.014	0.074	-10000	0	-10000	0	0
Rac1/GDP	0.041	0.048	-10000	0	-0.29	2	2
NGF (dimer)/TRKA/GRIT	-0.064	0.14	-10000	0	-0.35	95	95
neuron projection morphogenesis	-0.036	0.13	-10000	0	-0.5	12	12
NGF (dimer)/TRKA/NEDD4-2	-0.07	0.15	-10000	0	-0.35	104	104
MAP2K1	0.038	0.041	-10000	0	-0.53	1	1
NGFR	-0.064	0.19	-10000	0	-0.54	73	73
NGF (dimer)/TRKA/GIPC/GAIP	-0.049	0.14	-10000	0	-0.42	25	25
RAS family/GTP/PI3K	0.033	0.015	-10000	0	-0.26	1	1
FRS2 family/SHP2/GRB2/SOS1	-0.001	0.019	-10000	0	-10000	0	0
NRAS	0.014	0	-10000	0	-10000	0	0
GRB2/SOS1	-0.001	0.015	-10000	0	-0.34	1	1
PRKCI	0.014	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.014	0	-10000	0	-10000	0	0
PRKCZ	-0.015	0.13	-10000	0	-0.55	27	27
MAPKKK cascade	-0.084	0.2	-10000	0	-0.61	60	60
RASA1	0.014	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.016	0.074	-10000	0	-0.36	22	22
SQSTM1	0.014	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.064	0.12	-10000	0	-0.36	43	43
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.064	0.13	-10000	0	-0.34	70	70
MATK	-0.093	0.22	-10000	0	-0.55	98	98
NEDD4L	0	0.088	-10000	0	-0.53	14	14
RAS family/GDP	-0.004	0.021	-10000	0	-0.26	1	1
NGF (dimer)/TRKA	-0.074	0.13	-10000	0	-0.33	91	91
Rac1/GTP	-0.064	0.095	-10000	0	-0.31	40	40
FRS2 family/SHP2/CRK family	-0.001	0.019	-10000	0	-10000	0	0

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.018	0.006	-9999	-10000	0	0
RAS family/GTP	-0.07	0.15	-9999	-0.51	25	25
NFATC4	-0.06	0.13	-9999	-0.37	35	35
ERBB2IP	0.015	0.027	-9999	-0.59	1	1
HSP90 (dimer)	0.014	0	-9999	-10000	0	0
mammary gland morphogenesis	-0.089	0.15	-9999	-0.47	27	27
JUN	-0.02	0.1	-9999	-0.36	19	19
HRAS	0.014	0.001	-9999	-10000	0	0
DOCK7	-0.082	0.15	-9999	-0.46	30	30
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.12	0.18	-9999	-0.37	141	141
AKT1	0.01	0.004	-9999	-10000	0	0
BAD	0.02	0.003	-9999	-10000	0	0
MAPK10	-0.043	0.079	-9999	-0.24	28	28
mol:GTP	-0.001	0.002	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.094	0.17	-9999	-0.51	27	27
RAF1	-0.063	0.15	-9999	-0.49	25	25
ErbB2/ErbB3/neuregulin 2	-0.043	0.12	-9999	-0.34	57	57
STAT3	0.004	0.005	-9999	-10000	0	0
cell migration	-0.02	0.094	-9999	-0.24	24	24
mol:PI-3-4-5-P3	-0.002	0.003	-9999	-10000	0	0
cell proliferation	-0.15	0.27	-9999	-0.6	99	99
FOS	-0.12	0.22	-9999	-0.42	145	145
NRAS	0.014	0.001	-9999	-10000	0	0
mol:Ca2+	-0.089	0.15	-9999	-0.47	27	27
MAPK3	-0.12	0.22	-9999	-0.51	86	86
MAPK1	-0.12	0.22	-9999	-0.51	86	86
JAK2	-0.079	0.15	-9999	-0.44	27	27
NF2	-0.003	0.006	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.09	0.18	-9999	-0.33	140	140
NRG1	-0.17	0.27	-9999	-0.56	164	164
GRB2/SOS1	0.008	0.019	-9999	-0.34	1	1
MAPK8	-0.076	0.15	-9999	-0.38	39	39
MAPK9	-0.041	0.076	-9999	-0.23	25	25
ERBB2	-0.006	0.047	-9999	-0.38	8	8
ERBB3	-0.058	0.19	-9999	-0.57	62	62
SHC1	0.009	0.049	-9999	-0.49	5	5
RAC1	0.014	0	-9999	-10000	0	0
apoptosis	-0.001	0.011	-9999	-10000	0	0
STAT3 (dimer)	0.01	0.009	-9999	-10000	0	0
RNF41	0.023	0.009	-9999	-10000	0	0
FRAP1	0.009	0.003	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.071	0.097	-9999	-0.33	26	26
ErbB2/ErbB2/HSP90 (dimer)	-0.005	0.038	-9999	-0.31	8	8
CHRNA1	-0.14	0.26	-9999	-0.58	103	103
myelination	-0.053	0.13	-9999	-0.36	35	35
PPP3CB	-0.075	0.14	-9999	-0.4	29	29
KRAS	0.013	0.022	-9999	-0.49	1	1
RAC1-CDC42/GDP	-0.063	0.16	-9999	-0.51	26	26
NRG2	0.012	0.038	-9999	-0.59	2	2
mol:GDP	-0.09	0.17	-9999	-0.33	140	140
SOS1	0.014	0.001	-9999	-10000	0	0
MAP2K2	-0.06	0.15	-9999	-0.42	40	40
SRC	0.014	0	-9999	-10000	0	0
mol:cAMP	-0.002	0.002	-9999	-10000	0	0
PTPN11	-0.079	0.15	-9999	-0.44	27	27
MAP2K1	-0.13	0.22	-9999	-0.55	57	57
heart morphogenesis	-0.089	0.15	-9999	-0.47	27	27
RAS family/GDP	-0.067	0.15	-9999	-0.51	25	25
GRB2	0.013	0.022	-9999	-0.49	1	1
PRKACA	-0.007	0.009	-9999	-10000	0	0
CHRNE	0.002	0.044	-9999	-0.19	21	21
HSP90AA1	0.014	0	-9999	-10000	0	0
activation of caspase activity	-0.01	0.004	-9999	-10000	0	0
nervous system development	-0.089	0.15	-9999	-0.47	27	27
CDC42	0.014	0	-9999	-10000	0	0

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.014	0	-9999	-10000	0	0
VLDLR	-0.007	0.11	-9999	-0.57	19	19
LRPAP1	0.014	0	-9999	-10000	0	0
NUDC	0.014	0	-9999	-10000	0	0
RELN/LRP8	-0.089	0.15	-9999	-0.32	141	141
CaM/Ca2+	-0.002	0.025	-9999	-0.4	2	2
KATNA1	0.014	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.052	0.15	-9999	-0.32	79	79
IQGAP1/CaM	-0.009	0.057	-9999	-0.38	12	12
DAB1	-0.089	0.22	-9999	-0.56	92	92
IQGAP1	0.004	0.075	-9999	-0.53	10	10
PLA2G7	-0.039	0.17	-9999	-0.55	48	48
CALM1	0.012	0.035	-9999	-0.54	2	2
DYNLT1	0.012	0.038	-9999	-0.59	2	2
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.002	0.027	-9999	-0.43	2	2
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.014	0	-9999	-10000	0	0
CDK5R1	-0.022	0.14	-9999	-0.59	31	31
LIS1/Poliovirus Protein 3A	0.018	0	-9999	-10000	0	0
CDK5R2	-0.1	0.23	-9999	-0.57	104	104
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.16	0.21	-9999	-0.39	212	212
YWHAE	0.014	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.07	0.19	-9999	-0.54	43	43
MAP1B	-0.001	0.016	-9999	-0.31	1	1
RAC1	-0.003	0.019	-9999	-10000	0	0
p35/CDK5	-0.048	0.16	-9999	-0.57	16	16
RELN	-0.14	0.25	-9999	-0.55	140	140
PAFAH/LIS1	-0.004	0.1	-9999	-0.33	48	48
LIS1/CLIP170	0.029	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.08	0.13	-9999	-0.44	39	39
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.085	0.2	-9999	-0.64	34	34
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.083	0.2	-9999	-0.54	54	54
LIS1/IQGAP1	0.022	0.047	-9999	-0.31	10	10
RHOA	-0.003	0.019	-9999	-10000	0	0
PAFAH1B1	0.025	0	-9999	-10000	0	0
PAFAH1B3	0.014	0	-9999	-10000	0	0
PAFAH1B2	-0.005	0.1	-9999	-0.59	16	16
MAP1B/LIS1/Dynein heavy chain	0.027	0.011	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.1	0.16	-9999	-0.52	43	43
LRP8	0.012	0.038	-9999	-0.59	2	2
NDEL1/Katanin 60	-0.07	0.19	-9999	-0.54	43	43
P39/CDK5	-0.089	0.19	-9999	-0.53	41	41
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.029	0	-9999	-10000	0	0
CDK5	-0.039	0.14	-9999	-0.29	79	79
PPP2R5D	0.014	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0	-9999	-10000	0	0
CSNK2A1	0.014	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.1	0.2	-9999	-0.36	148	148
RELN/VLDLR	-0.09	0.14	-9999	-0.34	93	93
CDC42	-0.003	0.019	-9999	-10000	0	0

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0	0.093	-9999	-0.32	40	40
EPHB2	0	0.087	-9999	-0.52	14	14
Syndecan-2/TACI	-0.011	0.086	-9999	-0.33	33	33
LAMA1	-0.063	0.2	-9999	-0.57	68	68
Syndecan-2/alpha2 ITGB1	-0.027	0.15	-9999	-0.38	55	55
HRAS	0.014	0	-9999	-10000	0	0
Syndecan-2/CASK	-0.015	0.071	-9999	-0.34	23	23
ITGA5	-0.01	0.11	-9999	-0.5	24	24
BAX	0.02	0.087	-9999	-10000	0	0
EPB41	0.011	0.044	-9999	-0.56	3	3
positive regulation of cell-cell adhesion	-0.013	0.062	-9999	-0.3	23	23
LAMA3	-0.041	0.17	-9999	-0.54	51	51
EZR	0.004	0.079	-9999	-0.59	9	9
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.015	0.12	-9999	-0.5	30	30
Syndecan-2/MMP2	-0.006	0.1	-9999	-0.33	47	47
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.034	0.11	-9999	-0.38	46	46
dendrite morphogenesis	0.002	0.096	-9999	-0.35	34	34
Syndecan-2/GM-CSF	-0.014	0.071	-9999	-0.34	23	23
determination of left/right symmetry	0.003	0.088	-9999	-0.4	23	23
Syndecan-2/PKC delta	-0.009	0.12	-9999	-0.4	43	43
GNB2L1	0.014	0	-9999	-10000	0	0
MAPK3	0.012	0.068	-9999	-0.3	23	23
MAPK1	0.012	0.068	-9999	-0.32	16	16
Syndecan-2/RACK1	-0.012	0.058	-9999	-0.28	23	23
NF1	0.012	0.038	-9999	-0.59	2	2
FGFR/FGF/Syndecan-2	0.003	0.088	-9999	-0.4	23	23
ITGA2	-0.033	0.16	-9999	-0.54	44	44
MAPK8	0.011	0.097	-9999	-0.34	37	37
Syndecan-2/alpha2/beta1 Integrin	-0.039	0.17	-9999	-0.38	79	79
Syndecan-2/Kininogen	-0.02	0.093	-9999	-0.31	47	47
ITGB1	0.012	0.031	-9999	-0.49	2	2
SRC	0.027	0.061	-9999	-0.28	16	16
Syndecan-2/CASK/Protein 4.1	-0.015	0.071	-9999	-0.33	24	24
extracellular matrix organization	0.004	0.093	-9999	-0.36	30	30
actin cytoskeleton reorganization	0	0.093	-9999	-0.32	40	40
Syndecan-2/Caveolin-2/Ras	0.003	0.096	-9999	-0.34	20	20
Syndecan-2/Laminin alpha3	-0.023	0.13	-9999	-0.35	69	69
Syndecan-2/RasGAP	-0.011	0.053	-9999	-0.28	16	16
alpha5/beta1 Integrin	-0.017	0.079	-9999	-0.36	25	25
PRKCD	-0.018	0.14	-9999	-0.59	27	27
Syndecan-2 dimer	0.002	0.096	-9999	-0.35	34	34
GO:0007205	0.004	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.034	0.06	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
SDCBP	0.014	0	-9999	-10000	0	0
TNFRSF13B	-0.005	0.072	-9999	-0.49	11	11
RASA1	0.014	0	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.034	0.11	-9999	-0.38	46	46
Syndecan-2/Synbindin	0.011	0.074	-9999	-0.33	23	23
TGFB1	0.004	0.079	-9999	-0.59	9	9
CASP3	0.002	0.12	-9999	-0.38	36	36
FN1	-0.003	0.092	-9999	-0.49	18	18
Syndecan-2/IL8	-0.095	0.18	-9999	-0.33	176	176
SDC2	0.003	0.088	-9999	-0.4	23	23
KNG1	-0.019	0.1	-9999	-0.49	24	24
Syndecan-2/Neurofibromin	0.009	0.08	-9999	-0.35	24	24
TRAPPC4	0.014	0	-9999	-10000	0	0
CSF2	0.001	0.003	-9999	-10000	0	0
Syndecan-2/TGFB1	0.004	0.094	-9999	-0.36	30	30
Syndecan-2/Syntenin/PI-4-5-P2	-0.013	0.063	-9999	-0.3	23	23
Syndecan-2/Ezrin	0.014	0.093	-9999	-0.4	20	20
PRKACA	0.019	0.073	-9999	-0.31	24	24
angiogenesis	-0.095	0.18	-9999	-0.33	176	176
MMP2	-0.012	0.12	-9999	-0.54	25	25
IL8	-0.16	0.26	-9999	-0.53	162	162
calcineurin-NFAT signaling pathway	-0.011	0.085	-9999	-0.33	33	33

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.03	0.13	-9999	-0.41	24	24
FZD6	-0.014	0.12	-9999	-0.49	29	29
WNT6	-0.033	0.16	-9999	-0.53	45	45
WNT4	-0.033	0.15	-9999	-0.52	46	46
FZD3	0.011	0.046	-9999	-0.59	3	3
WNT5A	-0.013	0.12	-9999	-0.56	24	24
WNT11	-0.017	0.13	-9999	-0.54	29	29

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.014	0.027	-9999	-0.59	1	1
ELF1	-0.016	0.091	-9999	-0.37	9	9
CCNA2	-0.055	0.18	-9999	-0.53	66	66
PIK3CA	0.014	0.027	-9999	-0.59	1	1
JAK3	-0.056	0.18	-9999	-0.53	68	68
PIK3R1	0.015	0.001	-9999	-10000	0	0
JAK1	0.015	0.001	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.025	0.16	-9999	-0.39	50	50
SHC1	0.01	0.049	-9999	-0.49	5	5
SP1	0.016	0.044	-9999	-0.34	4	4
IL2RA	-0.043	0.18	-9999	-0.46	74	74
IL2RB	-0.094	0.22	-9999	-0.53	103	103
SOS1	0.015	0.001	-9999	-10000	0	0
IL2RG	-0.04	0.16	-9999	-0.52	53	53
G1/S transition of mitotic cell cycle	-0.034	0.18	-9999	-0.49	50	50
PTPN11	0.015	0.001	-9999	-10000	0	0
CCND2	0.019	0.095	-9999	-0.54	13	13
LCK	-0.08	0.21	-9999	-0.53	89	89
GRB2	0.014	0.022	-9999	-0.49	1	1
IL2	0.001	0.003	-9999	-10000	0	0
CDK6	-0.033	0.16	-9999	-0.54	44	44
CCND3	-0.012	0.14	-9999	-0.48	6	6

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.008	0.066	-9999	-0.31	21	21
ADCY5	0	0.091	-9999	-0.37	28	28
ADCY6	0.014	0.048	-9999	-0.31	11	11
ADCY7	0.014	0.048	-9999	-0.31	11	11
ADCY1	-0.053	0.15	-9999	-0.35	103	103
ADCY2	0.004	0.081	-9999	-0.36	24	24
ADCY3	0.014	0.048	-9999	-0.31	11	11
ADCY8	-0.03	0.13	-9999	-0.36	71	71
PRKCE	0.004	0.056	-9999	-0.38	11	11
ADCY9	0.012	0.06	-9999	-0.34	14	14
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.008	0.098	-9999	-0.35	22	22

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.01	0.056	-10000	0	-0.59	4	4
HSPA8	0.013	0.027	-10000	0	-0.59	1	1
SMAD3/SMAD4/ER alpha	-0.026	0.1	0.21	2	-0.39	25	27
AKT1	0.008	0.023	-10000	0	-10000	0	0
GSC	-0.17	0.49	-10000	0	-1.4	68	68
NKX2-5	-0.092	0.2	-10000	0	-0.5	102	102
muscle cell differentiation	0.15	0.19	0.47	98	-10000	0	98
SMAD2-3/SMAD4/SP1	-0.007	0.11	-10000	0	-0.42	8	8
SMAD4	-0.017	0.066	-10000	0	-0.34	2	2
CBFB	0.014	0	-10000	0	-10000	0	0
SAP18	0.014	0.002	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.023	0.11	-10000	0	-0.33	48	48
SMAD3/SMAD4/VDR	-0.034	0.12	-10000	0	-0.37	20	20
MYC	-0.009	0.13	-10000	0	-0.55	26	26
CDKN2B	-0.13	0.45	-10000	0	-1.4	56	56
AP1	-0.03	0.16	-10000	0	-0.53	25	25
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.043	0.063	-10000	0	-0.54	2	2
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.012	0.14	-10000	0	-0.4	27	27
SP3	0.016	0.008	-10000	0	-10000	0	0
CREB1	0.014	0	-10000	0	-10000	0	0
FOXH1	-0.016	0.1	-10000	0	-0.56	16	16
SMAD3/SMAD4/GR	-0.01	0.062	-10000	0	-0.42	1	1
GATA3	-0.13	0.24	-10000	0	-0.56	115	115
SKI/SIN3/HDAC complex/NCoR1	0.045	0.036	-10000	0	-0.36	1	1
MEF2C/TIF2	-0.076	0.18	-10000	0	-0.51	43	43
endothelial cell migration	0.22	0.48	1.3	77	-10000	0	77
MAX	0.023	0.019	-10000	0	-10000	0	0
RBBP7	0.014	0.003	-10000	0	-10000	0	0
RBBP4	0.013	0.027	-10000	0	-0.59	1	1
RUNX2	-0.005	0.1	-10000	0	-0.53	18	18
RUNX3	-0.03	0.15	-10000	0	-0.55	40	40
RUNX1	-0.053	0.18	-10000	0	-0.53	64	64
CTBP1	0.014	0	-10000	0	-10000	0	0
NR3C1	0.023	0.019	-10000	0	-10000	0	0
VDR	-0.065	0.19	-10000	0	-0.53	74	74
CDKN1A	-0.045	0.28	-10000	0	-1.2	22	22
KAT2B	0.013	0.023	-10000	0	-0.49	1	1
SMAD2/SMAD2/SMAD4/FOXH1	-0.027	0.12	-10000	0	-0.38	24	24
DCP1A	0.014	0	-10000	0	-10000	0	0
SKI	0.014	0.002	-10000	0	-10000	0	0
SERPINE1	-0.22	0.49	-10000	0	-1.4	72	72
SMAD3/SMAD4/ATF2	-0.028	0.081	-10000	0	-0.38	15	15
SMAD3/SMAD4/ATF3	-0.05	0.12	-10000	0	-0.39	46	46
SAP30	0.013	0.027	-10000	0	-0.6	1	1
Cbp/p300/PIAS3	0.015	0.057	-10000	0	-0.36	4	4
JUN	-0.024	0.16	-10000	0	-0.52	25	25
SMAD3/SMAD4/IRF7	-0.033	0.097	-10000	0	-0.41	20	20
TFE3	0.008	0.029	-10000	0	-10000	0	0
COL1A2	-0.044	0.16	-10000	0	-0.46	58	58
mesenchymal cell differentiation	0.03	0.09	0.41	18	-10000	0	18
DLX1	-0.16	0.26	-10000	0	-0.54	161	161
TCF3	0.012	0.038	-10000	0	-0.59	2	2
FOS	-0.093	0.23	-10000	0	-0.55	101	101
SMAD3/SMAD4/Max	-0.01	0.062	-10000	0	-0.36	2	2
Cbp/p300/SNIP1	0.007	0.039	-10000	0	-0.36	4	4
ZBTB17	0.019	0.019	-10000	0	-10000	0	0
LAMC1	0.001	0.11	-10000	0	-0.49	18	18
TGIF2/HDAC complex/SMAD3/SMAD4	-0.023	0.073	-10000	0	-0.43	8	8
IRF7	-0.01	0.11	-10000	0	-0.52	23	23
ESR1	-0.013	0.12	-10000	0	-0.54	26	26
HNF4A	-0.034	0.14	-10000	0	-0.49	42	42
MEF2C	-0.063	0.17	-10000	0	-0.51	32	32
SMAD2-3/SMAD4	-0.035	0.073	-10000	0	-0.36	8	8
Cbp/p300/Src-1	0.01	0.045	-10000	0	-0.36	4	4
IGHV3OR16-13	-0.015	0.032	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.007	0.063	-10000	0	-0.57	6	6
CREBBP	0.015	0.012	-10000	0	-10000	0	0
SKIL	0.006	0.07	-10000	0	-0.59	7	7
HDAC1	0.009	0.053	-10000	0	-0.59	4	4
HDAC2	0.014	0.002	-10000	0	-10000	0	0
SNIP1	0.014	0.005	-10000	0	-10000	0	0
GCN5L2	-0.001	0.016	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	-0.009	0.083	-10000	0	-0.4	5	5
MSG1/HSC70	-0.022	0.12	-10000	0	-0.37	55	55
SMAD2	-0.004	0.047	-10000	0	-10000	0	0
SMAD3	-0.005	0.056	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.009	0.073	-10000	0	-0.33	7	7
SMAD2/SMAD2/SMAD4	-0.003	0.033	-10000	0	-10000	0	0
NCOR1	0.012	0.038	-10000	0	-0.59	2	2
NCOA2	-0.027	0.15	-10000	0	-0.59	35	35
NCOA1	0.014	0	-10000	0	-10000	0	0
MYOD/E2A	-0.14	0.19	-10000	0	-0.39	180	180
SMAD2-3/SMAD4/SP1/MIZ-1	0.004	0.11	-10000	0	-0.47	5	5
IFNB1	-0.007	0.1	-10000	0	-0.48	10	10
SMAD3/SMAD4/MEF2C	-0.067	0.18	-10000	0	-0.51	32	32
CITED1	-0.043	0.17	-10000	0	-0.53	54	54
SMAD2-3/SMAD4/ARC105	-0.011	0.074	-10000	0	-0.34	5	5
RBL1	-0.007	0.11	-10000	0	-0.57	19	19
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.027	0.19	-10000	0	-0.53	57	57
RUNX1-3/PEBPB2	-0.063	0.14	-10000	0	-0.35	94	94
SMAD7	-0.012	0.15	-10000	0	-0.56	8	8
MYC/MIZ-1	-0.002	0.1	-10000	0	-0.42	20	20
SMAD3/SMAD4	-0.041	0.19	0.3	39	-0.42	62	101
IL10	-0.14	0.28	-10000	0	-0.62	109	109
PIASy/HDAC complex	0.016	0.014	-10000	0	-10000	0	0
PIAS3	0.013	0.007	-10000	0	-10000	0	0
CDK2	0.001	0.086	-10000	0	-0.53	13	13
IL5	-0.085	0.19	-10000	0	-0.51	42	42
CDK4	-0.001	0.089	-10000	0	-0.49	16	16
PIAS4	0.016	0.013	-10000	0	-10000	0	0
ATF3	-0.038	0.16	-10000	0	-0.51	51	51
SMAD3/SMAD4/SP1	-0.009	0.1	-10000	0	-0.42	7	7
FOXG1	-0.025	0.15	-10000	0	-0.59	34	34
FOXO3	0.017	0.032	-10000	0	-10000	0	0
FOXO1	0.014	0.045	-10000	0	-0.42	3	3
FOXO4	0.016	0.039	-10000	0	-0.51	1	1
heart looping	-0.062	0.17	-10000	0	-0.51	32	32
CEBPB	-0.008	0.11	-10000	0	-0.57	17	17
SMAD3/SMAD4/DLX1	-0.12	0.17	-10000	0	-0.37	156	156
MYOD1	-0.18	0.27	-10000	0	-0.55	178	178
SMAD3/SMAD4/HNF4	-0.045	0.1	-10000	0	-0.38	21	21
SMAD3/SMAD4/GATA3	-0.13	0.19	-10000	0	-0.47	79	79
SnoN/SIN3/HDAC complex/NCoR1	0.006	0.07	-10000	0	-0.59	7	7
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.061	0.14	-10000	0	-0.41	47	47
SMAD3/SMAD4/SP1-3	0.009	0.098	-10000	0	-0.41	7	7
MED15	0.014	0	-10000	0	-10000	0	0
SP1	0.005	0.041	-10000	0	-10000	0	0
SIN3B	0.014	0.003	-10000	0	-10000	0	0
SIN3A	0.014	0.002	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.073	0.16	-10000	0	-0.44	34	34
ITGB5	0.02	0.11	-10000	0	-0.66	6	6
TGIF/SIN3/HDAC complex/CtBP	0.043	0.043	-10000	0	-0.44	1	1
SMAD3/SMAD4/AR	-0.092	0.16	-10000	0	-0.38	97	97
AR	-0.1	0.23	-10000	0	-0.56	107	107
negative regulation of cell growth	-0.007	0.12	-10000	0	-0.43	20	20
SMAD3/SMAD4/MYOD	-0.14	0.18	-10000	0	-0.39	135	135
E2F5	0.011	0.046	-10000	0	-0.59	3	3
E2F4	0.014	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.007	0.097	-10000	0	-0.34	13	13
SMAD2-3/SMAD4/FOXO1-3a-4	-0.01	0.13	-10000	0	-0.37	42	42
TFDP1	0.013	0.027	-10000	0	-0.59	1	1
SMAD3/SMAD4/AP1	-0.03	0.16	-10000	0	-0.53	25	25
SMAD3/SMAD4/RUNX2	-0.03	0.091	-10000	0	-0.42	17	17
TGIF2	0.007	0.063	-10000	0	-0.58	6	6
TGIF1	-0.008	0.11	-10000	0	-0.53	21	21
ATF2	-0.001	0.095	-10000	0	-0.59	13	13

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.044	0.15	-10000	0	-0.72	19	19
HDAC1	0.008	0.054	-10000	0	-0.59	4	4
AES	0.014	0.004	-10000	0	-10000	0	0
FBXW11	0.014	0	-10000	0	-10000	0	0
DTX1	0.004	0.078	-10000	0	-0.58	9	9
LRP6/FZD1	-0.005	0.04	-10000	0	-0.34	7	7
TLE1	0.012	0.038	-10000	0	-0.6	2	2
AP1	-0.029	0.12	-10000	0	-0.3	70	70
NCSTN	0.014	0	-10000	0	-10000	0	0
ADAM10	0	0.092	-10000	0	-0.59	12	12
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.027	0.072	-10000	0	-10000	0	0
NICD/RBPSUH	-0.02	0.11	-10000	0	-0.59	19	19
WIF1	-0.28	0.28	-10000	0	-0.54	271	271
NOTCH1	-0.023	0.12	-10000	0	-0.63	19	19
PSENEN	0.014	0	-10000	0	-10000	0	0
KREMEN2	-0.052	0.18	-10000	0	-0.53	63	63
DKK1	-0.12	0.24	-10000	0	-0.53	123	123
beta catenin/beta TrCP1	0.017	0.046	0.33	3	-10000	0	3
APH1B	0.014	0	-10000	0	-10000	0	0
APH1A	0.014	0	-10000	0	-10000	0	0
AXIN1	-0.001	0.045	0.23	4	-0.26	2	6
CtBP/CBP/TCF1/TLE1/AES	0.031	0.051	0.28	4	-10000	0	4
PSEN1	0.014	0	-10000	0	-10000	0	0
FOS	-0.096	0.22	-10000	0	-0.55	101	101
JUN	0.003	0.074	-10000	0	-0.5	11	11
MAP3K7	0.014	0.005	-10000	0	-10000	0	0
CTNNB1	0.009	0.049	0.32	4	-10000	0	4
MAPK3	0.014	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.11	0.17	-10000	0	-0.34	163	163
HNF1A	0.013	0.027	-10000	0	-0.59	1	1
CTBP1	0.014	0.004	-10000	0	-10000	0	0
MYC	-0.04	0.29	-10000	0	-1.4	22	22
NKD1	-0.004	0.099	-10000	0	-0.54	17	17
FZD1	0.008	0.054	-10000	0	-0.49	6	6
NOTCH1 precursor/Deltex homolog 1	-0.025	0.12	-10000	0	-0.6	19	19
apoptosis	-0.029	0.12	-10000	0	-0.29	70	70
Delta 1/NOTCHprecursor	-0.042	0.15	-10000	0	-0.71	19	19
DLL1	-0.033	0.16	-10000	0	-0.59	40	40
PPARD	0.02	0.027	-10000	0	-10000	0	0
Gamma Secretase	0	0	-10000	0	-10000	0	0
APC	-0.002	0.061	0.24	3	-0.49	3	6
DVL1	-0.021	0.024	-10000	0	-10000	0	0
CSNK2A1	0.014	0.003	-10000	0	-10000	0	0
MAP3K7IP1	-0.001	0.005	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.11	0.17	-10000	0	-0.34	168	168
LRP6	0.013	0.022	-10000	0	-0.49	1	1
CSNK1A1	0.014	0.003	-10000	0	-10000	0	0
NLK	0.016	0.015	-10000	0	-10000	0	0
CCND1	-0.021	0.22	-10000	0	-1.3	12	12
WNT1	-0.022	0.12	-10000	0	-0.49	34	34
Axin1/APC/beta catenin	0.018	0.061	0.31	4	-0.41	2	6
DKK2	-0.11	0.23	-10000	0	-0.54	117	117
NOTCH1 precursor/DVL1	-0.021	0.11	-10000	0	-0.56	19	19
GSK3B	0.013	0.027	-10000	0	-0.59	1	1
FRAT1	0.01	0.049	-10000	0	-0.54	4	4
NOTCH/Deltex homolog 1	-0.027	0.12	-10000	0	-0.62	19	19
PPP2R5D	-0.003	0.049	0.25	17	-10000	0	17
MAPK1	0.014	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.15	0.18	-10000	0	-0.37	139	139
RBPJ	0.013	0.022	-10000	0	-0.49	1	1
CREBBP	0.017	0.005	-10000	0	-10000	0	0

×

S1P5 pathway

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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.053	0.099	0.52	8	-10000	0	8
GNAI2	0.014	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.087	0.15	-10000	0	-0.34	134	134
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.008	0.059	-10000	0	-0.59	5	5
RhoA/GTP	-0.053	0.1	-10000	0	-0.53	8	8
negative regulation of cAMP metabolic process	-0.034	0.13	-10000	0	-0.28	80	80
GNAZ	0.014	0	-10000	0	-10000	0	0
GNAI3	0.014	0	-10000	0	-10000	0	0
GNA12	0.013	0.027	-10000	0	-0.59	1	1
S1PR5	-0.13	0.25	-10000	0	-0.55	134	134
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.034	0.13	-10000	0	-0.28	80	80
RhoA/GDP	0	0	-10000	0	-10000	0	0
RHOA	0.014	0	-10000	0	-10000	0	0
GNAI1	-0.005	0.1	-10000	0	-0.59	16	16

×

Signaling events mediated by HDAC Class III

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
EP300	0.009	0.053	-10000	0	-0.59	4	4
HDAC4	0.014	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.027	0.037	0.34	3	-10000	0	3
CDKN1A	-0.052	0.17	-10000	0	-0.48	60	60
KAT2B	0.013	0.022	-10000	0	-0.49	1	1
BAX	0.014	0	-10000	0	-10000	0	0
FOXO3	0.004	0.04	0.45	4	-10000	0	4
FOXO1	0.011	0.044	-10000	0	-0.56	3	3
FOXO4	0.022	0.031	-10000	0	-0.29	5	5
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.014	0	-10000	0	-10000	0	0
TAT	-0.08	0.21	-10000	0	-0.54	88	88
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.12	0.2	-10000	0	-0.39	178	178
PPARGC1A	-0.011	0.12	-10000	0	-0.57	22	22
FHL2	-0.032	0.15	-10000	0	-0.52	45	45
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.012	0.035	-10000	0	-10000	0	0
HIST2H4A	0.027	0.037	-10000	0	-0.34	3	3
SIRT1/FOXO3a	0.013	0.039	0.29	4	-10000	0	4
SIRT1	0.016	0.045	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.011	0.039	-10000	0	-0.28	2	2
SIRT1/Histone H1b	-0.002	0.069	-10000	0	-0.26	19	19
apoptosis	-0.012	0.034	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.004	0.08	-10000	0	-0.35	22	22
p53/SIRT1	0.023	0.12	0.4	19	-0.43	13	32
SIRT1/FOXO4	0.011	0.046	-10000	0	-0.25	4	4
FOXO1/FHL2/SIRT1	-0.015	0.089	-10000	0	-0.28	42	42
HIST1H1E	0.003	0.073	-10000	0	-0.3	20	20
SIRT1/p300	0.009	0.052	-10000	0	-0.43	4	4
muscle cell differentiation	0.1	0.16	0.32	177	-10000	0	177
TP53	-0.002	0.11	-10000	0	-0.57	15	15
KU70/SIRT1/BAX	0.012	0.035	-10000	0	-10000	0	0
CREBBP	0.014	0	-10000	0	-10000	0	0
MEF2D	0.012	0.031	-10000	0	-0.49	2	2
HIV-1 Tat/SIRT1	-0.054	0.15	-10000	0	-0.38	88	88
ACSS2	0.029	0.024	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	-0.1	0.16	-10000	0	-0.32	177	177

×

FAS signaling pathway (CD95)

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
SPTAN1	0.008	0.057	0.27	8	-10000	0	8
RFC1	0.008	0.057	0.22	21	-10000	0	21
PRKDC	0.008	0.057	0.27	8	-10000	0	8
RIPK1	0.016	0.003	-10000	0	-10000	0	0
CASP7	-0.004	0.071	0.25	15	-0.31	6	21
FASLG/FAS/FADD/FAF1	-0.009	0.085	0.22	19	-0.31	15	34
MAP2K4	-0.003	0.12	-10000	0	-0.36	15	15
mol:ceramide	-0.003	0.096	-10000	0	-0.39	11	11
GSN	0	0.072	0.25	6	-0.34	10	16
FASLG/FAS/FADD/FAF1/Caspase 8	-0.001	0.09	-10000	0	-0.34	14	14
FAS	-0.008	0.1	-10000	0	-0.55	18	18
BID	0.005	0.079	0.3	17	-0.3	12	29
MAP3K1	0.009	0.09	0.22	14	-0.29	8	22
MAP3K7	0.012	0.004	-10000	0	-10000	0	0
RB1	0.008	0.059	0.27	8	-0.36	1	9
CFLAR	0.015	0.022	-10000	0	-0.47	1	1
HGF/MET	-0.15	0.2	-10000	0	-0.44	114	114
ARHGDIB	0.006	0.063	0.27	8	-0.36	3	11
FADD	0.011	0.007	-10000	0	-10000	0	0
actin filament polymerization	0	0.071	0.34	10	-0.25	6	16
NFKB1	-0.039	0.067	-10000	0	-0.26	4	4
MAPK8	-0.028	0.17	-10000	0	-0.42	53	53
DFFA	0.008	0.057	0.22	21	-10000	0	21
DNA fragmentation during apoptosis	0.008	0.057	0.27	8	-10000	0	8
FAS/FADD/MET	-0.1	0.16	-10000	0	-0.34	158	158
CFLAR/RIP1	0.014	0.017	-10000	0	-0.32	1	1
FAIM3	-0.027	0.15	-10000	0	-0.54	39	39
FAF1	0.01	0.027	-10000	0	-0.59	1	1
PARP1	0.008	0.059	0.27	8	-0.28	1	9
DFFB	0.008	0.057	0.27	8	-10000	0	8
CHUK	-0.033	0.057	-10000	0	-10000	0	0
FASLG	-0.026	0.12	-10000	0	-0.5	33	33
FAS/FADD	0.002	0.077	-10000	0	-0.4	18	18
HGF	-0.079	0.2	-10000	0	-0.51	91	91
LMNA	0.006	0.061	0.25	8	-0.31	5	13
CASP6	0.007	0.064	0.27	8	-0.38	3	11
CASP10	0.01	0.024	-10000	0	-0.5	1	1
CASP3	0.01	0.068	0.26	24	-10000	0	24
PTPN13	0.006	0.069	-10000	0	-0.58	7	7
CASP8	0.01	0.1	0.31	34	-0.34	16	50
IL6	-0.14	0.38	-10000	0	-1.2	45	45
MET	-0.15	0.25	-10000	0	-0.54	151	151
ICAD/CAD	0.009	0.053	0.25	8	-10000	0	8
FASLG/FAS/FADD/FAF1/Caspase 10	-0.003	0.097	-10000	0	-0.39	11	11
activation of caspase activity by cytochrome c	0.005	0.079	0.3	17	-0.3	12	29
PAK2	0.008	0.057	0.22	21	-10000	0	21
BCL2	0.005	0.075	-10000	0	-0.59	8	8

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.004	0.08	-10000	0	-0.59	9	9
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.004	0.1	0.44	6	-10000	0	6
IL27/IL27R/JAK1	-0.034	0.15	-10000	0	-0.53	9	9
TBX21	-0.057	0.21	-10000	0	-0.54	45	45
IL12B	-0.002	0.054	-10000	0	-0.49	6	6
IL12A	-0.012	0.1	-10000	0	-0.42	29	29
IL6ST	-0.028	0.16	-10000	0	-0.6	36	36
IL27RA/JAK1	0.018	0.035	-10000	0	-10000	0	0
IL27	-0.015	0.11	-10000	0	-0.49	27	27
TYK2	0.015	0.003	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.055	0.12	-10000	0	-0.72	2	2
T-helper 2 cell differentiation	0.004	0.1	0.44	6	-10000	0	6
T cell proliferation during immune response	0.004	0.1	0.44	6	-10000	0	6
MAPKKK cascade	-0.004	0.1	-10000	0	-0.44	6	6
STAT3	0.014	0	-10000	0	-10000	0	0
STAT2	0.01	0.044	-10000	0	-0.49	4	4
STAT1	-0.002	0.088	-10000	0	-0.49	16	16
IL12RB1	-0.031	0.16	-10000	0	-0.56	41	41
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.087	0.24	-10000	0	-0.53	58	58
IL27/IL27R/JAK2/TYK2	-0.004	0.1	-10000	0	-0.44	6	6
positive regulation of T cell mediated cytotoxicity	-0.004	0.1	-10000	0	-0.44	6	6
STAT1 (dimer)	-0.059	0.24	0.52	27	-0.61	26	53
JAK2	0.015	0.004	-10000	0	-10000	0	0
JAK1	0.014	0.004	-10000	0	-10000	0	0
STAT2 (dimer)	0.002	0.1	-10000	0	-0.4	7	7
T cell proliferation	-0.068	0.16	-10000	0	-0.48	20	20
IL12/IL12R/TYK2/JAK2	-0.005	0.091	-10000	0	-0.56	4	4
IL17A	-0.055	0.12	-10000	0	-0.72	2	2
mast cell activation	0.004	0.1	0.44	6	-10000	0	6
IFNG	0.001	0.02	-10000	0	-0.095	3	3
T cell differentiation	-0.004	0.005	-10000	0	-0.022	4	4
STAT3 (dimer)	0.004	0.096	-10000	0	-0.41	6	6
STAT5A (dimer)	-0.003	0.11	-10000	0	-0.46	11	11
STAT4 (dimer)	-0.086	0.17	-10000	0	-0.47	27	27
STAT4	-0.16	0.26	-10000	0	-0.53	166	166
T cell activation	-0.009	0.007	0.061	3	-10000	0	3
IL27R/JAK2/TYK2	-0.011	0.087	-10000	0	-10000	0	0
GATA3	-0.16	0.41	-10000	0	-1.4	51	51
IL18	-0.02	0.11	-10000	0	-0.4	41	41
positive regulation of mast cell cytokine production	0.004	0.095	-10000	0	-0.41	6	6
IL27/EBI3	-0.02	0.12	-10000	0	-0.4	46	46
IL27RA	0.014	0.034	-10000	0	-0.39	1	1
IL6	-0.13	0.24	-10000	0	-0.52	137	137
STAT5A	0.001	0.088	-10000	0	-0.59	11	11
monocyte differentiation	0	0	-10000	0	-10000	0	0
IL2	-0.001	0.02	-10000	0	-10000	0	0
IL1B	-0.12	0.19	-10000	0	-0.39	174	174
EBI3	-0.012	0.12	-10000	0	-0.57	22	22
TNF	-0.11	0.19	-10000	0	-0.39	156	156

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.008	0.059	-10000	0	-0.59	5	5
ANTXR2	0.002	0.079	-10000	0	-0.51	12	12
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.002	0.012	-10000	0	-0.066	17	17
monocyte activation	-0.16	0.25	-10000	0	-0.51	146	146
MAP2K2	-0.001	0.004	-10000	0	-10000	0	0
MAP2K1	-0.003	0.02	-10000	0	-0.29	2	2
MAP2K7	-0.002	0.009	-10000	0	-10000	0	0
MAP2K6	-0.002	0.017	-10000	0	-0.32	1	1
CYAA	0.007	0.052	-10000	0	-0.27	17	17
MAP2K4	-0.003	0.022	-10000	0	-0.32	2	2
IL1B	-0.082	0.14	-10000	0	-0.28	174	174
Channel	-0.01	0.052	-10000	0	-0.29	17	17
NLRP1	-0.003	0.022	-10000	0	-0.32	2	2
CALM1	0.012	0.035	-10000	0	-0.54	2	2
negative regulation of phagocytosis	-0.004	0.028	-10000	0	-0.54	1	1
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.002	0.012	0.066	17	-10000	0	17
MAPK3	-0.002	0.009	-10000	0	-10000	0	0
MAPK1	-0.002	0.009	-10000	0	-10000	0	0
PGR	-0.034	0.099	-10000	0	-0.32	53	53
PA/Cellular Receptors	-0.011	0.058	-10000	0	-0.32	17	17
apoptosis	-0.002	0.012	-10000	0	-0.066	17	17
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.009	0.051	-10000	0	-0.26	17	17
macrophage activation	0.019	0.011	-10000	0	-10000	0	0
TNF	-0.15	0.26	-10000	0	-0.54	156	156
VCAM1	-0.16	0.26	-10000	0	-0.52	146	146
platelet activation	-0.004	0.028	-10000	0	-0.54	1	1
MAPKKK cascade	-0.015	0.017	0.18	2	-10000	0	2
IL18	-0.009	0.088	-10000	0	-0.29	41	41
negative regulation of macrophage activation	-0.002	0.012	-10000	0	-0.066	17	17
LEF	-0.002	0.012	-10000	0	-0.066	17	17
CASP1	-0.004	0.022	-10000	0	-0.27	2	2
mol:cAMP	-0.004	0.028	-10000	0	-0.55	1	1
necrosis	-0.002	0.012	-10000	0	-0.066	17	17
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.008	0.052	-10000	0	-0.27	17	17
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.035	0.16	-9999	-0.46	60	60
KLHL20	-0.026	0.056	-9999	-0.27	9	9
CYFIP2	0.008	0.06	-9999	-0.54	6	6
Rac1/GDP	0.008	0.11	-9999	-10000	0	0
ENAH	-0.035	0.16	-9999	-0.46	60	60
AP1M1	0.014	0	-9999	-10000	0	0
RAP1B	0.013	0.022	-9999	-0.49	1	1
RAP1A	0.014	0	-9999	-10000	0	0
CTNNB1	0.014	0	-9999	-10000	0	0
CDC42/GTP	-0.035	0.066	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.017	0.038	-9999	-0.18	11	11
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.092	0.15	-9999	-0.38	74	74
RAPGEF1	-0.014	0.14	-9999	-0.39	60	60
CTNND1	0.014	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.073	0.16	-9999	-0.48	60	60
CRK	-0.024	0.16	-9999	-0.43	60	60
E-cadherin/gamma catenin/alpha catenin	-0.083	0.15	-9999	-0.37	66	66
alphaE/beta7 Integrin	-0.033	0.11	-9999	-0.38	45	45
IQGAP1	0.004	0.075	-9999	-0.53	10	10
NCKAP1	0.014	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	-0.001	0.018	-9999	-0.33	1	1
DLG1	-0.035	0.16	-9999	-0.46	61	61
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.026	0.048	-9999	-10000	0	0
MLLT4	0.013	0.027	-9999	-0.59	1	1
ARF6/GTP/NME1/Tiam1	0	0.015	-9999	-0.33	1	1
PI3K	-0.032	0.061	-9999	-10000	0	0
ARF6	0.014	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.1	0.18	-9999	-0.39	132	132
TIAM1	0.013	0.027	-9999	-0.59	1	1
E-cadherin(dimer)/Ca2+	-0.064	0.11	-9999	-0.3	60	60
AKT1	-0.018	0.035	-9999	-10000	0	0
PIK3R1	0.014	0	-9999	-10000	0	0
CDH1	-0.12	0.24	-9999	-0.54	125	125
RhoA/GDP	0.008	0.11	-9999	-10000	0	0
actin cytoskeleton organization	-0.02	0.041	-9999	-0.19	9	9
CDC42/GDP	0.008	0.11	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.032	0.11	-9999	-0.27	66	66
ITGB7	-0.034	0.16	-9999	-0.54	45	45
RAC1	0.014	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.041	0.14	-9999	-0.32	60	60
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.066	0.12	-9999	-0.27	125	125
mol:GDP	-0.002	0.12	-9999	-0.32	8	8
CDC42/GTP/IQGAP1	-0.006	0.044	-9999	-0.32	10	10
JUP	0.003	0.081	-9999	-0.57	10	10
p120 catenin/RhoA/GDP	-0.042	0.086	-9999	-10000	0	0
RAC1/GTP/IQGAP1	-0.006	0.044	-9999	-0.32	10	10
PIP5K1C/AP1M1	0	0	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
CDC42	0.014	0	-9999	-10000	0	0
CTNNA1	0.014	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.01	0.063	-9999	-0.21	29	29
NME1	0.014	0	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	-0.035	0.16	-9999	-0.46	60	60
regulation of cell-cell adhesion	-0.032	0.059	-9999	-10000	0	0
WASF2	-0.008	0.02	-9999	-10000	0	0
Rap1/GTP	-0.041	0.077	-9999	-0.32	1	1
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.09	0.15	-9999	-0.58	19	19
CCND1	0.011	0.077	-9999	-0.26	29	29
VAV2	-0.018	0.15	-9999	-0.42	60	60
RAP1/GDP	-0.039	0.081	-9999	-10000	0	0
adherens junction assembly	-0.033	0.16	-9999	-0.44	60	60
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.014	0	-9999	-10000	0	0
PIP5K1C	0.014	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.051	0.16	-9999	-0.55	19	19
E-cadherin/beta catenin	-0.067	0.13	-9999	-0.39	60	60
mol:GTP	0	0	-9999	-10000	0	0
SRC	-0.036	0.16	-9999	-0.46	60	60
PIK3CA	0.013	0.027	-9999	-0.59	1	1
Rac1/GTP	-0.042	0.089	-9999	-0.45	9	9
E-cadherin/beta catenin/alpha catenin	-0.077	0.14	-9999	-0.32	125	125
ITGAE	0.014	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.075	0.16	-9999	-0.49	60	60

×

IL2 signaling events mediated by PI3K

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
BCL2L1	-0.037	0.16	-10000	0	-0.53	14	14
UGCG	-0.022	0.14	-10000	0	-0.67	20	20
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.039	0.16	-10000	0	-0.4	44	44
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.021	0.13	-10000	0	-0.66	20	20
mol:DAG	-0.004	0.043	-10000	0	-0.97	1	1
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.069	0.12	-10000	0	-0.45	28	28
FRAP1	-0.027	0.18	-10000	0	-0.53	27	27
FOXO3	-0.019	0.17	-10000	0	-0.51	22	22
AKT1	-0.03	0.18	-10000	0	-0.46	43	43
GAB2	0.013	0.027	-10000	0	-0.6	1	1
SMPD1	0.004	0.036	-10000	0	-10000	0	0
SGMS1	0.003	0.046	-10000	0	-0.67	1	1
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	0.022	0.018	-10000	0	-0.36	1	1
CALM1	0.012	0.035	-10000	0	-0.54	2	2
cell proliferation	-0.015	0.11	-10000	0	-0.3	44	44
EIF3A	0.014	0	-10000	0	-10000	0	0
PI3K	0.024	0.021	-10000	0	-0.43	1	1
RPS6KB1	-0.004	0.065	-10000	0	-0.25	1	1
mol:sphingomyelin	-0.004	0.043	-10000	0	-0.97	1	1
natural killer cell activation	0	0.002	-10000	0	-0.013	1	1
JAK3	-0.055	0.18	-10000	0	-0.52	68	68
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
JAK1	0.016	0.003	-10000	0	-10000	0	0
NFKB1	0.014	0	-10000	0	-10000	0	0
MYC	-0.04	0.24	-10000	0	-0.93	26	26
MYB	-0.095	0.35	-10000	0	-1	54	54
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.037	0.17	-10000	0	-0.4	58	58
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.013	0.061	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.035	0.16	-10000	0	-0.39	58	58
Rac1/GDP	0.028	0.017	-10000	0	-0.32	1	1
T cell proliferation	-0.037	0.18	-10000	0	-0.46	46	46
SHC1	0.009	0.05	-10000	0	-0.49	5	5
RAC1	0.014	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	-0.002	0.02	-10000	0	-0.05	73	73
PRKCZ	-0.039	0.18	-10000	0	-0.48	46	46
NF kappa B1 p50/RelA	-0.062	0.12	-10000	0	-0.47	22	22
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.05	0.17	-10000	0	-0.43	58	58
HSP90AA1	0.014	0	-10000	0	-10000	0	0
RELA	0.014	0	-10000	0	-10000	0	0
IL2RA	-0.063	0.18	-10000	0	-0.5	73	73
IL2RB	-0.092	0.22	-10000	0	-0.53	103	103
TERT	-0.082	0.21	-10000	0	-0.56	81	81
E2F1	-0.032	0.15	-10000	0	-0.43	56	56
SOS1	0.014	0.004	-10000	0	-10000	0	0
RPS6	0.013	0.022	-10000	0	-0.49	1	1
mol:cAMP	0.001	0.01	0.024	73	-10000	0	73
PTPN11	0.014	0.004	-10000	0	-10000	0	0
IL2RG	-0.039	0.16	-10000	0	-0.52	53	53
actin cytoskeleton organization	-0.037	0.18	-10000	0	-0.46	46	46
GRB2	0.013	0.022	-10000	0	-0.49	1	1
IL2	0.003	0.004	-10000	0	-10000	0	0
PIK3CA	0.015	0.027	-10000	0	-0.59	1	1
Rac1/GTP	0.032	0.022	-10000	0	-0.3	1	1
LCK	-0.078	0.21	-10000	0	-0.53	89	89
BCL2	-0.015	0.18	-10000	0	-0.7	15	15

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.003	0.058	-10000	0	-0.58	4	4
AES	0.011	0.022	-10000	0	-10000	0	0
FBXW11	0.014	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	-0.001	0.04	-10000	0	-0.34	7	7
SMAD4	0.014	0	-10000	0	-10000	0	0
DKK2	-0.11	0.23	-10000	0	-0.54	117	117
TLE1	0.008	0.044	-10000	0	-0.6	2	2
MACF1	0.015	0	-10000	0	-10000	0	0
CTNNB1	0.062	0.082	-10000	0	-10000	0	0
WIF1	-0.28	0.28	-10000	0	-0.54	271	271
beta catenin/RanBP3	0.021	0.11	0.39	33	-10000	0	33
KREMEN2	-0.052	0.18	-10000	0	-0.53	63	63
DKK1	-0.12	0.24	-10000	0	-0.53	123	123
beta catenin/beta TrCP1	0.067	0.077	-10000	0	-10000	0	0
FZD1	0.009	0.054	-10000	0	-0.49	6	6
AXIN2	-0.002	0.11	-10000	0	-0.9	5	5
AXIN1	0.015	0.001	-10000	0	-10000	0	0
RAN	0.014	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.023	0.044	-10000	0	-0.56	1	1
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.091	0.052	0.29	3	-10000	0	3
Axin1/APC/GSK3	0.008	0.037	0.25	3	-10000	0	3
Axin1/APC/GSK3/beta catenin/Macf1	0.054	0.065	-10000	0	-10000	0	0
HNF1A	0.006	0.036	-10000	0	-0.6	1	1
CTBP1	0.007	0.024	-10000	0	-10000	0	0
MYC	-0.052	0.31	-10000	0	-1.5	22	22
RANBP3	0.014	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.11	0.17	-10000	0	-0.34	163	163
NKD1	-0.004	0.099	-10000	0	-0.54	17	17
TCF4	0.006	0.034	-10000	0	-0.55	1	1
TCF3	0.005	0.04	-10000	0	-0.53	2	2
WNT1/LRP6/FZD1/Axin1	-0.017	0.068	-10000	0	-0.5	1	1
Ran/GTP	0.002	0.005	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.034	0.13	0.49	31	-10000	0	31
LEF1	0.002	0.054	-10000	0	-0.49	5	5
DVL1	0.061	0.047	-10000	0	-10000	0	0
CSNK2A1	0.014	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.087	0.078	-10000	0	-0.44	2	2
DKK1/LRP6/Kremen 2	-0.11	0.17	-10000	0	-0.35	153	153
LRP6	0.014	0.022	-10000	0	-0.49	1	1
CSNK1A1	0.009	0.026	-10000	0	-10000	0	0
NLK	0.012	0.033	-10000	0	-0.51	2	2
CCND1	-0.034	0.24	-10000	0	-1.4	12	12
WNT1	-0.021	0.12	-10000	0	-0.49	34	34
GSK3A	0.015	0.001	-10000	0	-10000	0	0
GSK3B	0.013	0.027	-10000	0	-0.59	1	1
FRAT1	0.01	0.049	-10000	0	-0.54	4	4
PPP2R5D	0.043	0.049	0.27	17	-10000	0	17
APC	0.022	0.073	-10000	0	-0.38	2	2
WNT1/LRP6/FZD1	0.098	0.1	0.24	112	-10000	0	112
CREBBP	0.007	0.024	-10000	0	-10000	0	0

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.067	0.2	-9999	-0.55	74	74
GNB1/GNG2	-0.014	0.12	-9999	-0.42	20	20
mol:DAG	-0.004	0.12	-9999	-0.38	19	19
PLCG1	-0.004	0.12	-9999	-0.39	19	19
YES1	-0.022	0.13	-9999	-0.43	22	22
FZD3	0.011	0.046	-9999	-0.59	3	3
FZD6	-0.014	0.12	-9999	-0.49	29	29
G protein	-0.005	0.12	-9999	-0.4	19	19
MAP3K7	-0.098	0.16	-9999	-0.41	44	44
mol:Ca2+	-0.003	0.11	-9999	-0.37	19	19
mol:IP3	-0.004	0.12	-9999	-0.38	19	19
NLK	-0.004	0.011	-9999	-10000	0	0
GNB1	0.014	0	-9999	-10000	0	0
CAMK2A	-0.11	0.17	-9999	-0.44	46	46
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.03	0.13	-9999	-0.41	24	24
CSNK1A1	0.014	0	-9999	-10000	0	0
GNAS	-0.019	0.12	-9999	-0.41	20	20
GO:0007205	-0.003	0.11	-9999	-0.43	10	10
WNT6	-0.033	0.16	-9999	-0.53	45	45
WNT4	-0.033	0.15	-9999	-0.52	46	46
NFAT1/CK1 alpha	-0.037	0.16	-9999	-0.45	37	37
GNG2	0.009	0.053	-9999	-0.59	4	4
WNT5A	-0.013	0.12	-9999	-0.56	24	24
WNT11	-0.017	0.13	-9999	-0.54	29	29
CDC42	-0.012	0.12	-9999	-0.41	21	21

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.014	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.004	0.043	-9999	-0.82	1	1
Syndecan-3/Neurocan	-0.021	0.082	-9999	-0.32	31	31
POMC	-0.005	0.1	-9999	-0.54	18	18
EGFR	-0.083	0.21	-9999	-0.55	89	89
Syndecan-3/EGFR	-0.047	0.1	-9999	-0.3	50	50
AGRP	0.005	0.049	-9999	-0.49	5	5
NCSTN	0.014	0	-9999	-10000	0	0
PSENEN	0.014	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.014	0	-9999	-10000	0	0
APH1A	0.014	0	-9999	-10000	0	0
NCAN	-0.026	0.15	-9999	-0.58	35	35
long-term memory	-0.002	0.026	-9999	-0.56	1	1
Syndecan-3/IL8	-0.082	0.12	-9999	-0.3	68	68
PSEN1	0.014	0	-9999	-10000	0	0
Src/Cortactin	0	0	-9999	-10000	0	0
FYN	0.014	0	-9999	-10000	0	0
limb bud formation	-0.002	0.029	-9999	-0.62	1	1
MC4R	-0.11	0.24	-9999	-0.56	112	112
SRC	0.014	0	-9999	-10000	0	0
PTN	0.007	0.062	-9999	-0.52	7	7
FGFR/FGF/Syndecan-3	-0.002	0.029	-9999	-0.63	1	1
neuron projection morphogenesis	-0.021	0.08	-9999	-0.57	4	4
Syndecan-3/AgRP	-0.004	0.036	-9999	-0.61	1	1
Syndecan-3/AgRP/MC4R	-0.06	0.12	-9999	-0.56	3	3
Fyn/Cortactin	0	0	-9999	-10000	0	0
SDC3	-0.002	0.03	-9999	-0.64	1	1
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.081	0.12	-9999	-0.3	68	68
IL8	-0.16	0.26	-9999	-0.53	162	162
Syndecan-3/Fyn/Cortactin	-0.002	0.026	-9999	-0.57	1	1
Syndecan-3/CASK	-0.002	0.028	-9999	-0.61	1	1
alpha-MSH/MC4R	-0.1	0.18	-9999	-0.42	123	123
Gamma Secretase	0	0	-9999	-10000	0	0

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.021	0.087	-9999	-0.37	29	29
alphaV beta3 Integrin	-0.04	0.1	-9999	-0.31	67	67
PTK2	-0.012	0.15	-9999	-0.46	23	23
IGF1R	0.013	0.022	-9999	-0.49	1	1
PI4KB	0.014	0	-9999	-10000	0	0
MFGE8	0.01	0.051	-9999	-0.57	4	4
SRC	0.014	0	-9999	-10000	0	0
CDKN1B	-0.028	0.089	-9999	-0.49	15	15
VEGFA	-0.007	0.1	-9999	-0.49	22	22
ILK	-0.028	0.089	-9999	-0.49	15	15
ROCK1	0.014	0	-9999	-10000	0	0
AKT1	0.008	0.092	-9999	-0.45	15	15
PTK2B	-0.02	0.14	-9999	-0.41	35	35
alphaV/beta3 Integrin/JAM-A	-0.012	0.13	-9999	-0.35	36	36
CBL	0.014	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.039	0.1	-9999	-0.3	67	67
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.012	0.058	-9999	-0.32	14	14
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.011	0.085	-9999	-0.37	4	4
alphaV/beta3 Integrin/Syndecan-1	-0.063	0.14	-9999	-0.36	91	91
PI4KA	0.005	0.066	-9999	-0.49	9	9
IGF-1R heterotetramer/IGF1/IRS1	-0.045	0.11	-9999	-0.47	19	19
PI4 Kinase	-0.006	0.045	-9999	-0.34	9	9
PIK3CA	0.013	0.027	-9999	-0.59	1	1
alphaV/beta3 Integrin/Osteopontin	-0.093	0.16	-9999	-0.36	133	133
RPS6KB1	0.01	0.12	-9999	-0.44	19	19
TLN1	0.014	0	-9999	-10000	0	0
MAPK3	0.006	0.12	-9999	-0.44	23	23
GPR124	0.01	0.044	-9999	-0.49	4	4
MAPK1	0.006	0.12	-9999	-0.45	20	20
PXN	0.014	0	-9999	-10000	0	0
PIK3R1	0.014	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.086	0.16	-9999	-0.46	45	45
cell adhesion	-0.033	0.085	-9999	-0.34	14	14
ANGPTL3	0.005	0.023	-9999	-0.49	1	1
VEGFR2 homodimer/VEGFA homodimer/Src	-0.017	0.072	-9999	-0.31	29	29
IGF-1R heterotetramer	0.013	0.022	-9999	-0.49	1	1
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	0.009	0.049	-9999	-0.49	5	5
ITGB3	-0.052	0.18	-9999	-0.51	65	65
IGF1	-0.008	0.11	-9999	-0.56	20	20
RAC1	0.014	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.04	0.1	-9999	-0.38	16	16
apoptosis	0.013	0.027	-9999	-0.59	1	1
CD47	0.014	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.038	0.099	-9999	-0.3	66	66
VCL	0.008	0.058	-9999	-0.52	6	6
alphaV/beta3 Integrin/Del1	-0.083	0.16	-9999	-0.35	122	122
CSF1	-0.006	0.11	-9999	-0.59	17	17
PIK3C2A	-0.031	0.097	-9999	-0.5	17	17
PI4 Kinase/Pyk2	-0.057	0.12	-9999	-0.43	32	32
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.049	0.12	-9999	-0.43	35	35
FAK1/Vinculin	-0.003	0.13	-9999	-0.39	19	19
alphaV beta3/Integrin/ppsTEM5	-0.04	0.1	-9999	-0.38	16	16
RHOA	0.014	0	-9999	-10000	0	0
VTN	-0.008	0.11	-9999	-0.56	20	20
BCAR1	0.013	0.027	-9999	-0.59	1	1
FGF2	0.011	0.044	-9999	-0.56	3	3
F11R	0.014	0.065	-9999	-0.36	15	15
alphaV/beta3 Integrin/Lactadherin	-0.04	0.1	-9999	-0.3	70	70
alphaV/beta3 Integrin/TGFBR2	-0.04	0.11	-9999	-0.31	68	68
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.012	0.06	-9999	-0.32	19	19
HSP90AA1	0.014	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.034	0.09	-9999	-0.33	14	14
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.003	0.092	-9999	-0.49	18	18
alphaV/beta3 Integrin/Pyk2	-0.02	0.14	-9999	-0.41	35	35
SDC1	-0.031	0.15	-9999	-0.51	44	44
VAV3	-0.039	0.14	-9999	-0.55	6	6
PTPN11	0.014	0	-9999	-10000	0	0
IRS1	0.014	0	-9999	-10000	0	0
FAK1/Paxillin	0	0.12	-9999	-0.37	18	18
cell migration	0.008	0.12	-9999	-0.37	14	14
ITGAV	0.013	0.027	-9999	-0.59	1	1
PI3K	-0.042	0.097	-9999	-0.47	9	9
SPP1	-0.082	0.21	-9999	-0.54	90	90
KDR	0.005	0.071	-9999	-0.52	9	9
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.013	0.027	-9999	-0.59	1	1
COL4A3	-0.071	0.2	-9999	-0.52	82	82
angiogenesis	0.008	0.13	-9999	-0.46	20	20
Rac1/GTP	-0.062	0.11	-9999	-0.5	6	6
EDIL3	-0.065	0.2	-9999	-0.57	69	69
cell proliferation	-0.04	0.11	-9999	-0.31	68	68

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	-0.025	0.11	-10000	0	-0.26	68	68
epithelial cell differentiation	-0.063	0.11	-10000	0	-0.3	60	60
CYFIP2	0.008	0.06	-10000	0	-0.54	6	6
ENAH	0.009	0.1	-10000	0	-0.32	6	6
EGFR	-0.083	0.21	-10000	0	-0.55	89	89
EPHA2	-0.015	0.12	-10000	0	-0.5	30	30
MYO6	-0.027	0.12	-10000	0	-10000	0	0
CTNNB1	0.014	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.004	0.034	-10000	0	-0.32	6	6
AQP5	-0.14	0.18	-10000	0	-0.48	90	90
CTNND1	0.014	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.027	0.12	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.033	0.13	-10000	0	-0.53	3	3
EGF	-0.05	0.18	-10000	0	-0.56	58	58
NCKAP1	0.014	0	-10000	0	-10000	0	0
AQP3	-0.076	0.13	-10000	0	-0.47	25	25
cortical microtubule organization	-0.063	0.11	-10000	0	-0.3	60	60
GO:0000145	-0.025	0.12	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.064	0.11	-10000	0	-0.3	60	60
MLLT4	0.013	0.027	-10000	0	-0.59	1	1
ARF6/GDP	-0.057	0.095	-10000	0	-0.4	10	10
ARF6	0.014	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.017	0.066	-10000	0	-0.4	3	3
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.028	0.12	-10000	0	-0.35	11	11
PVRL2	0.012	0.035	-10000	0	-0.54	2	2
ZYX	-0.032	0.12	-10000	0	-0.52	1	1
ARF6/GTP	-0.015	0.059	-10000	0	-0.37	3	3
CDH1	-0.12	0.24	-10000	0	-0.54	125	125
EGFR/EGFR/EGF/EGF	-0.13	0.17	-10000	0	-0.52	47	47
RhoA/GDP	-0.058	0.1	-10000	0	-10000	0	0
actin cytoskeleton organization	-0.021	0.12	-10000	0	-0.54	1	1
IGF-1R heterotetramer	0.013	0.022	-10000	0	-0.49	1	1
GIT1	0.014	0	-10000	0	-10000	0	0
IGF1R	0.013	0.022	-10000	0	-0.49	1	1
IGF1	-0.008	0.11	-10000	0	-0.56	20	20
DIAPH1	-0.001	0.052	-10000	0	-0.65	3	3
Wnt receptor signaling pathway	0.063	0.11	0.3	60	-10000	0	60
RHOA	0.014	0	-10000	0	-10000	0	0
RhoA/GTP	-0.057	0.096	-10000	0	-0.4	10	10
CTNNA1	0.014	0	-10000	0	-10000	0	0
VCL	-0.022	0.12	-10000	0	-0.56	1	1
EFNA1	0.01	0.044	-10000	0	-0.49	4	4
LPP	-0.042	0.14	-10000	0	-0.45	10	10
Ephrin A1/EPHA2	-0.069	0.11	-10000	0	-0.46	9	9
SEC6/SEC8	-0.05	0.092	-10000	0	-0.47	3	3
MGAT3	-0.033	0.13	-10000	0	-0.54	3	3
HGF/MET	-0.16	0.18	-10000	0	-0.51	73	73
HGF	-0.079	0.2	-10000	0	-0.51	91	91
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.025	0.11	-10000	0	-0.26	68	68
actin cable formation	0.02	0.1	-10000	0	-0.32	3	3
KIAA1543	-0.063	0.17	-10000	0	-0.55	25	25
KIFC3	-0.028	0.12	-10000	0	-0.58	1	1
NCK1	0.013	0.027	-10000	0	-0.59	1	1
EXOC3	0.014	0	-10000	0	-10000	0	0
ACTN1	-0.045	0.14	-10000	0	-0.47	8	8
NCK1/GIT1	-0.001	0.019	-10000	0	-0.43	1	1
mol:GDP	-0.063	0.11	-10000	0	-0.3	60	60
EXOC4	0.014	0	-10000	0	-10000	0	0
STX4	-0.027	0.12	-10000	0	-0.28	60	60
PIP5K1C	-0.027	0.12	-10000	0	-10000	0	0
LIMA1	0.004	0.079	-10000	0	-0.59	9	9
ABI1	0.014	0	-10000	0	-10000	0	0
ROCK1	-0.001	0.11	-10000	0	-0.34	10	10
adherens junction assembly	-0.043	0.17	-10000	0	-0.52	25	25
IGF-1R heterotetramer/IGF1	-0.065	0.12	-10000	0	-0.54	8	8
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.002	0.031	-10000	0	-0.4	3	3
MET	-0.15	0.25	-10000	0	-0.54	151	151
PLEKHA7	-0.037	0.14	-10000	0	-0.56	6	6
mol:GTP	-0.017	0.065	-10000	0	-0.4	3	3
establishment of epithelial cell apical/basal polarity	0.004	0.11	-10000	0	-0.45	3	3
cortical actin cytoskeleton stabilization	-0.025	0.11	-10000	0	-0.26	68	68
regulation of cell-cell adhesion	-0.021	0.12	-10000	0	-0.54	1	1
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.025	0.11	-10000	0	-0.26	68	68

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.011	0.038	-10000	0	-0.49	3	3
Jak2/Leptin Receptor	-0.009	0.1	0.2	18	-0.43	12	30
PTP1B/AKT1	-0.005	0.084	-10000	0	-0.33	9	9
FYN	0.014	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.014	0.093	-10000	0	-0.32	16	16
EGFR	-0.084	0.22	-10000	0	-0.55	89	89
EGF/EGFR	-0.095	0.16	-10000	0	-0.39	91	91
CSF1	-0.006	0.11	-10000	0	-0.59	17	17
AKT1	0.014	0.002	-10000	0	-10000	0	0
INSR	0.014	0.002	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.007	0.09	-10000	0	-0.36	10	10
Insulin Receptor/Insulin	-0.025	0.059	-10000	0	-0.34	4	4
HCK	-0.007	0.11	-10000	0	-0.54	20	20
CRK	0.014	0	-10000	0	-10000	0	0
TYK2	-0.005	0.088	-10000	0	-0.35	9	9
EGF	-0.052	0.18	-10000	0	-0.56	58	58
YES1	0.009	0.053	-10000	0	-0.59	4	4
CAV1	-0.03	0.12	-10000	0	-0.34	35	35
TXN	0.011	0.023	-10000	0	-0.5	1	1
PTP1B/IRS1/GRB2	-0.001	0.084	-10000	0	-0.34	9	9
cell migration	0.014	0.093	0.32	16	-10000	0	16
STAT3	0.014	0.001	-10000	0	-10000	0	0
PRLR	-0.018	0.14	-10000	0	-0.56	31	31
ITGA2B	-0.043	0.17	-10000	0	-0.57	50	50
CSF1R	-0.022	0.14	-10000	0	-0.57	32	32
Prolactin Receptor/Prolactin	-0.018	0.1	-10000	0	-0.4	34	34
FGR	0.011	0.038	-10000	0	-0.49	3	3
PTP1B/p130 Cas	-0.007	0.089	-10000	0	-0.35	10	10
Crk/p130 Cas	-0.002	0.084	-10000	0	-0.34	9	9
DOK1	0.003	0.084	-10000	0	-0.33	9	9
JAK2	0.001	0.084	-10000	0	-0.34	13	13
Jak2/Leptin Receptor/Leptin	-0.11	0.18	-10000	0	-0.43	99	99
PIK3R1	0.014	0	-10000	0	-10000	0	0
PTPN1	-0.014	0.093	-10000	0	-0.32	16	16
LYN	0.004	0.073	-10000	0	-0.51	10	10
CDH2	0.013	0.027	-10000	0	-0.59	1	1
SRC	0.012	0.037	-10000	0	-10000	0	0
ITGB3	-0.052	0.18	-10000	0	-0.51	65	65
CAT1/PTP1B	-0.058	0.15	-10000	0	-0.43	33	33
CAPN1	0.014	0.027	-10000	0	-0.6	1	1
CSK	0.014	0	-10000	0	-10000	0	0
PI3K	-0.018	0.053	-10000	0	-0.35	2	2
mol:H2O2	0	0.004	-10000	0	-10000	0	0
STAT3 (dimer)	-0.11	0.18	-10000	0	-0.43	107	107
negative regulation of transcription	0.002	0.083	-10000	0	-0.34	13	13
FCGR2A	-0.031	0.15	-10000	0	-0.54	42	42
FER	-0.013	0.12	-10000	0	-0.6	22	22
alphaIIb/beta3 Integrin	-0.081	0.17	-10000	0	-0.41	107	107
BLK	-0.1	0.22	-10000	0	-0.52	113	113
Insulin Receptor/Insulin/Shc	-0.003	0.045	-10000	0	-0.32	9	9
RHOA	0.015	0.002	-10000	0	-10000	0	0
LEPR	0.001	0.089	-10000	0	-0.53	14	14
BCAR1	0.013	0.027	-10000	0	-0.59	1	1
p210 bcr-abl/Grb2	0.013	0.022	-10000	0	-0.49	1	1
mol:NADPH	0	0.004	-10000	0	-10000	0	0
TRPV6	-0.068	0.16	-10000	0	-0.43	49	49
PRL	0.001	0.038	-10000	0	-0.48	3	3
SOCS3	-0.14	0.34	-10000	0	-1.4	32	32
SPRY2	0.006	0.064	-10000	0	-0.5	8	8
Insulin Receptor/Insulin/IRS1	0	0.035	-10000	0	-0.36	4	4
CSF1/CSF1R	-0.029	0.14	-10000	0	-0.47	31	31
Ras protein signal transduction	0.019	0.034	-10000	0	-0.4	1	1
IRS1	0.014	0	-10000	0	-10000	0	0
INS	-0.005	0.056	-10000	0	-0.57	5	5
LEP	-0.002	0.058	-10000	0	-0.49	7	7
STAT5B	-0.003	0.084	-10000	0	-0.3	12	12
STAT5A	-0.006	0.088	-10000	0	-0.31	14	14
GRB2	0.013	0.022	-10000	0	-0.49	1	1
PDGFB-D/PDGFRB	-0.008	0.091	-10000	0	-0.33	15	15
CSN2	-0.001	0.042	-10000	0	-10000	0	0
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
LAT	-0.037	0.15	-10000	0	-0.48	46	46
YBX1	0.02	0.038	-10000	0	-0.58	2	2
LCK	-0.081	0.21	-10000	0	-0.54	89	89
SHC1	0.009	0.049	-10000	0	-0.49	5	5
NOX4	-0.065	0.19	-10000	0	-0.52	76	76

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.004	0.092	-9999	-0.37	29	29
PDGFRB	0.01	0.039	-9999	-0.5	3	3
SPHK1	-0.041	0.14	-9999	-0.75	18	18
mol:S1P	-0.041	0.12	-9999	-0.61	21	21
S1P1/S1P/Gi	-0.021	0.15	-9999	-0.35	65	65
GNAO1	0.007	0.06	-9999	-0.6	5	5
PDGFB-D/PDGFRB/PLCgamma1	-0.009	0.14	-9999	-0.53	11	11
PLCG1	-0.014	0.15	-9999	-0.54	11	11
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.01	0.039	-9999	-0.5	3	3
GNAI2	0.012	0.006	-9999	-10000	0	0
GNAI3	0.012	0.006	-9999	-10000	0	0
GNAI1	-0.007	0.11	-9999	-0.6	16	16
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.003	0.078	-9999	-0.31	29	29
S1P1/S1P	-0.051	0.11	-9999	-0.44	30	30
negative regulation of cAMP metabolic process	-0.019	0.15	-9999	-0.34	65	65
MAPK3	-0.038	0.21	-9999	-0.53	61	61
calcium-dependent phospholipase C activity	-0.001	0.004	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
KDR	0.004	0.071	-9999	-0.53	9	9
PLCB2	-0.016	0.13	-9999	-0.46	25	25
RAC1	0.014	0	-9999	-10000	0	0
RhoA/GTP	-0.042	0.094	-9999	-0.37	28	28
receptor internalization	-0.048	0.1	-9999	-0.4	30	30
PTGS2	-0.1	0.36	-9999	-1	63	63
Rac1/GTP	-0.042	0.094	-9999	-0.37	28	28
RHOA	0.014	0	-9999	-10000	0	0
VEGFA	-0.008	0.1	-9999	-0.49	22	22
negative regulation of T cell proliferation	-0.019	0.15	-9999	-0.34	65	65
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.012	0.006	-9999	-10000	0	0
MAPK1	-0.038	0.21	-9999	-0.53	61	61
S1P1/S1P/PDGFB-D/PDGFRB	-0.011	0.13	-9999	-0.42	29	29
ABCC1	0.01	0.045	-9999	-0.49	4	4

×

TCGA08_rtk_signaling

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
PDGFRA	-0.058	0.19	-10000	0	-0.58	63	63
HRAS	0.014	0	-10000	0	-10000	0	0
EGFR	-0.083	0.21	-10000	0	-0.55	89	89
AKT	0.02	0.045	-10000	0	-0.38	4	4
FOXO3	0.014	0	-10000	0	-10000	0	0
AKT1	0.014	0	-10000	0	-10000	0	0
FOXO1	0.011	0.044	-10000	0	-0.56	3	3
AKT3	0.008	0.059	-10000	0	-0.59	5	5
FOXO4	0.013	0.027	-10000	0	-0.59	1	1
MET	-0.15	0.25	-10000	0	-0.54	151	151
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
PIK3CB	0.014	0	-10000	0	-10000	0	0
NRAS	0.014	0	-10000	0	-10000	0	0
PIK3CG	-0.059	0.19	-10000	0	-0.53	69	69
PIK3R3	0.011	0.041	-10000	0	-0.52	3	3
PIK3R2	0.014	0	-10000	0	-10000	0	0
NF1	0.012	0.038	-10000	0	-0.59	2	2
RAS	-0.054	0.11	0.22	1	-0.29	54	55
ERBB2	0.005	0.068	-10000	0	-0.5	9	9
proliferation/survival/translation	-0.008	0.051	0.22	7	-10000	0	7
PI3K	-0.046	0.11	-10000	0	-0.26	68	68
PIK3R1	0.014	0	-10000	0	-10000	0	0
KRAS	0.013	0.022	-10000	0	-0.49	1	1
FOXO	0.028	0.03	-10000	0	-10000	0	0
AKT2	0.014	0	-10000	0	-10000	0	0
PTEN	0.013	0.027	-10000	0	-0.59	1	1

×

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

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
MAP4K1	0.011	0.12	-10000	0	-0.4	21	21
CRKL	0.02	0.11	-10000	0	-0.42	20	20
HRAS	0.002	0.14	-10000	0	-0.48	14	14
mol:PIP3	0.003	0.1	-10000	0	-0.39	21	21
SPRED1	0.014	0	-10000	0	-10000	0	0
SPRED2	0.011	0.038	-10000	0	-0.49	3	3
GAB1	0.013	0.12	-10000	0	-0.45	20	20
FOXO3	0.025	0.1	-10000	0	-0.38	18	18
AKT1	0.017	0.11	-10000	0	-0.4	20	20
BAD	0.025	0.1	-10000	0	-0.38	18	18
megakaryocyte differentiation	0.006	0.12	-10000	0	-0.39	32	32
GSK3B	0.024	0.1	-10000	0	-0.39	18	18
RAF1	0.014	0.12	-10000	0	-0.38	13	13
SHC1	0.009	0.049	-10000	0	-0.49	5	5
STAT3	0.014	0.11	-10000	0	-0.44	20	20
STAT1	0.004	0.24	-10000	0	-0.91	27	27
HRAS/SPRED1	0.011	0.12	-10000	0	-0.38	13	13
cell proliferation	0.006	0.13	-10000	0	-0.42	31	31
PIK3CA	0.013	0.027	-10000	0	-0.6	1	1
TEC	-0.004	0.1	-10000	0	-0.54	17	17
RPS6KB1	0.014	0.11	-10000	0	-0.38	29	29
HRAS/SPRED2	0.009	0.12	-10000	0	-0.38	15	15
LYN/TEC/p62DOK	-0.038	0.11	-10000	0	-0.45	28	28
MAPK3	0.025	0.089	-10000	0	-0.3	5	5
STAP1	-0.004	0.13	-10000	0	-0.43	31	31
GRAP2	-0.048	0.17	-10000	0	-0.53	58	58
JAK2	-0.05	0.18	-10000	0	-0.74	27	27
STAT1 (dimer)	0.006	0.23	-10000	0	-0.89	27	27
mol:Gleevec	-0.002	0.005	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.056	0.13	-10000	0	-0.46	31	31
actin filament polymerization	0.006	0.12	-10000	0	-0.39	29	29
LYN	0.004	0.073	-10000	0	-0.51	10	10
STAP1/STAT5A (dimer)	-0.004	0.18	-10000	0	-0.6	30	30
PIK3R1	0.014	0	-10000	0	-10000	0	0
CBL/CRKL/GRB2	0.029	0.1	-10000	0	-0.38	18	18
PI3K	0.022	0.11	-10000	0	-0.42	20	20
PTEN	0.013	0.027	-10000	0	-0.59	1	1
SCF/KIT/EPO/EPOR	-0.004	0.28	-10000	0	-1.2	21	21
MAPK8	0.005	0.13	-10000	0	-0.42	31	31
STAT3 (dimer)	0.014	0.11	-10000	0	-0.43	20	20
positive regulation of transcription	0.026	0.077	-10000	0	-0.24	5	5
mol:GDP	-0.062	0.12	0.22	2	-0.48	21	23
PIK3C2B	0.01	0.12	-10000	0	-0.42	24	24
CBL/CRKL	0.027	0.11	-10000	0	-0.39	20	20
FER	0.001	0.14	-10000	0	-0.43	36	36
SH2B3	0.013	0.11	-10000	0	-0.44	20	20
PDPK1	0.01	0.1	-10000	0	-0.38	20	20
SNAI2	-0.006	0.14	-10000	0	-0.42	33	33
positive regulation of cell proliferation	0.01	0.18	-10000	0	-0.69	27	27
KITLG	0.004	0.093	-10000	0	-0.6	12	12
cell motility	0.01	0.18	-10000	0	-0.69	27	27
PTPN6	-0.012	0.097	-10000	0	-0.55	16	16
EPOR	0.038	0.078	-10000	0	-10000	0	0
STAT5A (dimer)	0.008	0.16	-10000	0	-0.58	29	29
SOCS1	-0.031	0.15	-10000	0	-0.51	45	45
cell migration	0.04	0.16	0.36	71	-10000	0	71
SOS1	0.014	0	-10000	0	-10000	0	0
EPO	-0.006	0.099	-10000	0	-0.5	20	20
VAV1	-0.019	0.14	-10000	0	-0.56	30	30
GRB10	0.012	0.12	-10000	0	-0.42	22	22
PTPN11	0.013	0.005	-10000	0	-10000	0	0
SCF/KIT	0.006	0.12	0.23	9	-0.39	31	40
GO:0007205	-0.002	0.006	-10000	0	-10000	0	0
MAP2K1	0.022	0.097	-10000	0	-0.31	7	7
CBL	0.014	0	-10000	0	-10000	0	0
KIT	-0.009	0.27	-10000	0	-1.3	20	20
MAP2K2	0.022	0.097	-10000	0	-0.3	10	10
SHC/Grb2/SOS1	-0.028	0.092	-10000	0	-0.41	20	20
STAT5A	0.007	0.17	-10000	0	-0.6	29	29
GRB2	0.013	0.022	-10000	0	-0.49	1	1
response to radiation	-0.006	0.13	-10000	0	-0.42	33	33
SHC/GRAP2	-0.046	0.13	-10000	0	-0.39	61	61
PTPRO	0.005	0.13	-10000	0	-0.4	32	32
SH2B2	0.006	0.12	-10000	0	-0.39	29	29
DOK1	0.012	0.035	-10000	0	-0.54	2	2
MATK	-0.041	0.16	-10000	0	-0.37	71	71
CREBBP	0.039	0.012	-10000	0	-10000	0	0
BCL2	0.022	0.18	-10000	0	-1.3	8	8

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.005	0.095	-9999	-0.32	31	31
BIRC5	-0.14	0.25	-9999	-0.55	138	138
NFKBIA	0.029	0.049	-9999	-0.28	2	2
CPEB1	-0.002	0.099	-9999	-0.59	14	14
AKT1	0.029	0.049	-9999	-0.28	2	2
NDEL1	0.014	0	-9999	-10000	0	0
Aurora A/BRCA1	0.002	0.052	-9999	-0.32	6	6
NDEL1/TACC3	-0.013	0.092	-9999	-0.37	20	20
GADD45A	-0.018	0.12	-9999	-0.49	33	33
GSK3B	0.017	0.03	-9999	-0.6	1	1
PAK1/Aurora A	-0.005	0.1	-9999	-0.3	38	38
MDM2	0.012	0.031	-9999	-0.49	2	2
JUB	-0.013	0.12	-9999	-0.57	24	24
TPX2	-0.037	0.15	-9999	-0.38	80	80
TP53	0.021	0.062	-9999	-0.28	14	14
DLG7	0.018	0.049	-9999	-0.29	2	2
AURKAIP1	0.013	0.022	-9999	-0.49	1	1
ARHGEF7	0.014	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	0.009	0.1	-9999	-0.39	20	20
G2/M transition of mitotic cell cycle	0.002	0.052	-9999	-0.32	6	6
AURKA	0.023	0.061	-9999	-0.34	2	2
AURKB	-0.082	0.13	-9999	-0.29	126	126
CDC25B	0.024	0.048	-9999	-0.27	2	2
G2/M transition checkpoint	-0.011	0.073	-9999	-0.28	26	26
mRNA polyadenylation	-0.005	0.073	-9999	-0.36	15	15
Aurora A/CPEB	-0.005	0.074	-9999	-0.36	15	15
Aurora A/TACC1/TRAP/chTOG	0.011	0.047	-9999	-0.29	2	2
BRCA1	0.01	0.044	-9999	-0.49	4	4
centrosome duplication	-0.005	0.1	-9999	-0.3	38	38
regulation of centrosome cycle	-0.024	0.084	-9999	-0.36	20	20
spindle assembly	0.005	0.043	-9999	-0.28	2	2
TDRD7	0.012	0.038	-9999	-0.59	2	2
Aurora A/RasGAP/Survivin	-0.071	0.12	-9999	-0.32	65	65
CENPA	-0.056	0.13	-9999	-0.32	77	77
Aurora A/PP2A	0.025	0.047	-9999	-0.28	2	2
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.032	0.045	-9999	-0.26	2	2
negative regulation of DNA binding	0.021	0.062	-9999	-0.28	14	14
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0	0	-9999	-10000	0	0
RASA1	0.014	0	-9999	-10000	0	0
Ajuba/Aurora A	-0.011	0.074	-9999	-0.28	26	26
mitotic prometaphase	0.022	0.037	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.023	0.061	-9999	-0.34	2	2
TACC1	0.014	0	-9999	-10000	0	0
TACC3	-0.027	0.14	-9999	-0.5	42	42
Aurora A/Antizyme1	0.032	0.044	-9999	-10000	0	0
Aurora A/RasGAP	0.025	0.047	-9999	-0.28	2	2
OAZ1	0.014	0	-9999	-10000	0	0
RAN	0.014	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.018	0.014	-9999	-10000	0	0
GIT1	0.014	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	-0.027	0.085	-9999	-0.29	49	49
Importin alpha/Importin beta/TPX2	-0.037	0.15	-9999	-0.38	80	80
PPP2R5D	0.014	0	-9999	-10000	0	0
Aurora A/TPX2	-0.014	0.13	-9999	-0.36	43	43
PAK1	-0.035	0.15	-9999	-0.5	49	49
CKAP5	0.014	0	-9999	-10000	0	0

×

Ephrin B reverse signaling

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
EFNB2	0.002	0.08	-10000	0	-0.52	12	12
EPHB2	-0.001	0.087	-10000	0	-0.52	14	14
EFNB1	-0.063	0.17	-10000	0	-0.37	113	113
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.077	0.14	-10000	0	-0.58	20	20
Ephrin B2/EPHB1-2	-0.034	0.12	-10000	0	-0.34	61	61
neuron projection morphogenesis	-0.074	0.14	-10000	0	-0.55	20	20
Ephrin B1/EPHB1-2/Tiam1	-0.055	0.17	-10000	0	-0.61	21	21
DNM1	-0.1	0.22	-10000	0	-0.52	112	112
cell-cell signaling	0	0.002	-10000	0	-10000	0	0
MAP2K4	0.011	0.082	-10000	0	-0.72	6	6
YES1	-0.009	0.11	-10000	0	-1	6	6
Ephrin B1/EPHB1-2/NCK2	-0.054	0.17	-10000	0	-0.61	20	20
PI3K	0.012	0.083	-10000	0	-0.67	7	7
mol:GDP	-0.077	0.16	-10000	0	-0.61	20	20
ITGA2B	-0.043	0.17	-10000	0	-0.57	50	50
endothelial cell proliferation	-0.005	0.048	-10000	0	-0.31	12	12
FYN	-0.008	0.1	-10000	0	-0.94	6	6
MAP3K7	-0.007	0.083	-10000	0	-0.76	6	6
FGR	-0.008	0.1	-10000	0	-0.94	6	6
TIAM1	0.013	0.027	-10000	0	-0.59	1	1
PIK3R1	0.014	0	-10000	0	-10000	0	0
RGS3	0.011	0.038	-10000	0	-0.49	3	3
cell adhesion	-0.033	0.14	-10000	0	-0.59	14	14
LYN	-0.009	0.1	-10000	0	-0.94	6	6
Ephrin B1/EPHB1-2/Src Family Kinases	-0.011	0.098	-10000	0	-0.91	6	6
Ephrin B1/EPHB1-2	-0.013	0.089	-10000	0	-0.83	6	6
SRC	-0.007	0.1	-10000	0	-0.94	6	6
ITGB3	-0.052	0.18	-10000	0	-0.51	65	65
EPHB1	-0.036	0.17	-10000	0	-0.6	42	42
EPHB4	0.014	0	-10000	0	-10000	0	0
RAC1	0.014	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	-0.004	0.048	-10000	0	-0.31	12	12
alphaIIb/beta3 Integrin	-0.084	0.17	-10000	0	-0.41	107	107
BLK	-0.027	0.11	-10000	0	-0.98	6	6
HCK	-0.012	0.11	-10000	0	-1	6	6
regulation of stress fiber formation	0.076	0.16	0.6	20	-10000	0	20
MAPK8	0.01	0.096	-10000	0	-0.5	13	13
Ephrin B1/EPHB1-2/RGS3	-0.055	0.17	-10000	0	-0.62	21	21
endothelial cell migration	-0.008	0.082	-10000	0	-0.46	12	12
NCK2	0.014	0	-10000	0	-10000	0	0
PTPN13	0.003	0.082	-10000	0	-0.68	7	7
regulation of focal adhesion formation	0.076	0.16	0.6	20	-10000	0	20
chemotaxis	0.078	0.16	0.61	21	-10000	0	21
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
Rac1/GTP	-0.076	0.14	-10000	0	-0.57	20	20
angiogenesis	-0.013	0.089	-10000	0	-0.82	6	6
LCK	-0.026	0.11	-10000	0	-0.96	6	6

×

Sphingosine 1-phosphate (S1P) 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.014	0	-9999	-10000	0	0
SPHK1	-0.028	0.15	-9999	-0.54	40	40
GNAI2	0.014	0	-9999	-10000	0	0
mol:S1P	0.005	0.07	-9999	-0.3	20	20
GNAO1	0.008	0.059	-9999	-0.59	5	5
mol:Sphinganine-1-P	-0.007	0.11	-9999	-0.38	40	40
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.024	0.071	-9999	-0.5	4	4
GNAI3	0.014	0	-9999	-10000	0	0
G12/G13	-0.001	0.019	-9999	-0.43	1	1
S1PR3	-0.034	0.15	-9999	-0.52	47	47
S1PR2	0.008	0.062	-9999	-0.56	6	6
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.015	0.055	-9999	-0.26	20	20
S1PR5	-0.13	0.25	-9999	-0.55	134	134
S1PR4	0	0.086	-9999	-0.51	14	14
GNAI1	-0.005	0.1	-9999	-0.59	16	16
S1P/S1P5/G12	-0.063	0.16	-9999	-0.34	84	84
S1P/S1P3/Gq	-0.009	0.12	-9999	-0.48	15	15
S1P/S1P4/Gi	0.024	0.07	-9999	-0.37	6	6
GNAQ	0.014	0	-9999	-10000	0	0
GNAZ	0.014	0	-9999	-10000	0	0
GNA14	-0.014	0.12	-9999	-0.56	25	25
GNA15	-0.007	0.11	-9999	-0.57	19	19
GNA12	0.013	0.027	-9999	-0.59	1	1
GNA13	0.014	0	-9999	-10000	0	0
GNA11	0.004	0.079	-9999	-0.59	9	9
ABCC1	0.01	0.044	-9999	-0.49	4	4

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.013	0.022	-10000	0	-0.49	1	1
NFATC1	0.029	0.095	-10000	0	-0.44	2	2
NFATC2	0.009	0.078	-10000	0	-0.26	19	19
NFATC3	0.006	0.082	-10000	0	-0.4	17	17
YWHAE	0.014	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.064	0.18	-10000	0	-0.52	42	42
Exportin 1/Ran/NUP214	0	0	-10000	0	-10000	0	0
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.15	0.19	-10000	0	-0.48	91	91
BCL2/BAX	-0.007	0.053	-10000	0	-0.43	8	8
CaM/Ca2+/Calcineurin A alpha-beta B1	0.01	0.026	-10000	0	-0.4	2	2
CaM/Ca2+	0.01	0.026	-10000	0	-0.4	2	2
BAX	0.014	0	-10000	0	-10000	0	0
MAPK14	0.014	0.003	-10000	0	-10000	0	0
BAD	0.014	0	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.054	0.17	-10000	0	-0.49	43	43
Calcineurin A alpha-beta B1/BCL2	0.005	0.075	-10000	0	-0.59	8	8
FKBP8	0.014	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.053	0.16	0.48	43	-10000	0	43
KPNB1	0.014	0	-10000	0	-10000	0	0
KPNA2	0.012	0.031	-10000	0	-0.49	2	2
XPO1	0.014	0	-10000	0	-10000	0	0
SFN	-0.11	0.23	-10000	0	-0.53	119	119
MAP3K8	-0.005	0.1	-10000	0	-0.51	19	19
NFAT4/CK1 alpha	-0.015	0.057	-10000	0	-0.4	3	3
MEF2D/NFAT1/Cbp/p300	0.025	0.11	-10000	0	-0.43	13	13
CABIN1	-0.065	0.18	-10000	0	-0.53	42	42
CALM1	0.012	0.035	-10000	0	-0.54	2	2
RAN	0.014	0	-10000	0	-10000	0	0
MAP3K1	0.007	0.058	-10000	0	-0.49	7	7
CAMK4	-0.18	0.27	-10000	0	-0.57	168	168
mol:Ca2+	0	0.004	-10000	0	-10000	0	0
MAPK3	0.014	0	-10000	0	-10000	0	0
YWHAH	-0.01	0.11	-10000	0	-0.49	25	25
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.014	0.11	-10000	0	-0.35	48	48
YWHAB	0.014	0	-10000	0	-10000	0	0
MAPK8	-0.003	0.099	-10000	0	-0.59	14	14
MAPK9	0.014	0	-10000	0	-10000	0	0
YWHAG	0.002	0.079	-10000	0	-0.49	13	13
FKBP1A	0.014	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.037	0.1	-10000	0	-0.4	7	7
PRKCH	0.014	0	-10000	0	-10000	0	0
CABIN1/Cbp/p300	-0.003	0.038	-10000	0	-0.43	4	4
CASP3	0.013	0.022	-10000	0	-0.49	1	1
PIM1	0.008	0.054	-10000	0	-0.49	6	6
Calcineurin A alpha-beta B1/FKBP12/FK506	0.01	0.003	-10000	0	-10000	0	0
apoptosis	-0.002	0.021	-10000	0	-0.34	1	1
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.005	0.077	-10000	0	-0.31	4	4
PRKCB	-0.062	0.19	-10000	0	-0.52	73	73
PRKCE	0.003	0.077	-10000	0	-0.52	11	11
JNK2/NFAT4	0.014	0.075	-10000	0	-0.36	17	17
BAD/BCL-XL	-0.001	0.015	-10000	0	-0.34	1	1
PRKCD	-0.018	0.14	-10000	0	-0.59	27	27
NUP214	0.014	0	-10000	0	-10000	0	0
PRKCZ	-0.016	0.13	-10000	0	-0.55	27	27
PRKCA	0.013	0.027	-10000	0	-0.59	1	1
PRKCG	-0.19	0.27	-10000	0	-0.54	193	193
PRKCQ	-0.005	0.11	-10000	0	-0.58	17	17
FKBP38/BCL2	-0.007	0.053	-10000	0	-0.43	8	8
EP300	0.01	0.053	-10000	0	-0.59	4	4
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.014	0	-10000	0	-10000	0	0
NFATc/JNK1	0.026	0.1	-10000	0	-0.42	4	4
CaM/Ca2+/FKBP38	0.018	0.023	-10000	0	-0.33	2	2
FKBP12/FK506	0	0	-10000	0	-10000	0	0
CSNK1A1	0.02	0.023	-10000	0	-0.33	2	2
CaM/Ca2+/CAMK IV	-0.1	0.17	-10000	0	-0.35	169	169
NFATc/ERK1	0.036	0.091	-10000	0	-0.41	2	2
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.15	0.19	-10000	0	-0.48	91	91
NR4A1	0.018	0.14	-10000	0	-0.46	35	35
GSK3B	0.013	0.027	-10000	0	-0.59	1	1
positive T cell selection	0.006	0.082	-10000	0	-0.4	17	17
NFAT1/CK1 alpha	-0.02	0.05	-10000	0	-0.34	5	5
RCH1/ KPNB1	-0.001	0.021	-10000	0	-0.34	2	2
YWHAQ	0.014	0	-10000	0	-10000	0	0
PRKACA	0.014	0.003	-10000	0	-10000	0	0
AKAP5	-0.033	0.15	-10000	0	-0.5	48	48
MEF2D	0.012	0.032	-10000	0	-0.5	2	2
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.014	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.034	0.091	-10000	0	-0.41	2	2
CREBBP	0.014	0.002	-10000	0	-10000	0	0
BCL2	0.005	0.075	-10000	0	-0.59	8	8

×

ErbB4 signaling events

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
ErbB4/ErbB4/HBEGF/HBEGF	0.017	0.068	-10000	0	-0.36	3	3
epithelial cell differentiation	-0.042	0.086	-10000	0	-0.47	7	7
ITCH	0.019	0.013	-10000	0	-10000	0	0
WWP1	0.024	0.05	-10000	0	-10000	0	0
FYN	0.014	0	-10000	0	-10000	0	0
EGFR	-0.083	0.21	-10000	0	-0.55	89	89
PRL	-0.001	0.038	-10000	0	-0.49	3	3
neuron projection morphogenesis	-0.031	0.15	-10000	0	-0.46	12	12
PTPRZ1	0.005	0.072	-10000	0	-0.57	8	8
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.089	0.13	-10000	0	-0.52	12	12
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.078	0.17	-10000	0	-0.42	27	27
ADAM17	0.011	0.066	-10000	0	-0.59	6	6
ErbB4/ErbB4	0.02	0.064	-10000	0	-0.41	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.004	0.12	-10000	0	-0.38	39	39
NCOR1	0.012	0.038	-10000	0	-0.59	2	2
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.065	0.16	-10000	0	-0.43	16	16
GRIN2B	-0.15	0.21	-10000	0	-0.5	82	82
ErbB4/ErbB2/betacellulin	-0.031	0.14	-10000	0	-0.46	15	15
STAT1	-0.001	0.087	-10000	0	-0.49	16	16
HBEGF	0.004	0.069	-10000	0	-0.49	10	10
PRLR	-0.02	0.14	-10000	0	-0.56	31	31
E4ICDs/ETO2	0.018	0.07	-10000	0	-0.37	8	8
axon guidance	-0.016	0.078	-10000	0	-0.37	1	1
NEDD4	0.007	0.08	-10000	0	-0.52	11	11
Prolactin receptor/Prolactin receptor/Prolactin	-0.026	0.1	-10000	0	-0.4	34	34
CBFA2T3	0.006	0.07	-10000	0	-0.59	7	7
ErbB4/ErbB2/HBEGF	0.022	0.075	-10000	0	-0.48	1	1
MAPK3	-0.041	0.15	-10000	0	-0.48	12	12
STAT1 (dimer)	0.014	0.075	-10000	0	-0.39	4	4
MAPK1	-0.041	0.15	-10000	0	-0.48	12	12
JAK2	0.014	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.07	0.16	-10000	0	-0.5	13	13
NRG1	-0.11	0.21	-10000	0	-0.41	167	167
NRG3	-0.031	0.16	-10000	0	-0.59	38	38
NRG2	0.012	0.038	-10000	0	-0.59	2	2
NRG4	-0.046	0.17	-10000	0	-0.52	58	58
heart development	-0.016	0.078	-10000	0	-0.37	1	1
neural crest cell migration	-0.069	0.16	-10000	0	-0.44	20	20
ERBB2	0.016	0.069	-10000	0	-0.38	15	15
WWOX/E4ICDs	0.023	0.054	-10000	0	-0.36	1	1
SHC1	0.009	0.049	-10000	0	-0.49	5	5
ErbB4/EGFR/neuregulin 4	-0.057	0.16	-10000	0	-0.47	35	35
apoptosis	0.041	0.11	0.41	39	-10000	0	39
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	0.021	0.061	-10000	0	-0.44	3	3
ErbB4/ErbB2/epiregulin	0.005	0.086	-10000	0	-0.49	3	3
ErbB4/ErbB4/betacellulin/betacellulin	-0.04	0.14	-10000	0	-0.36	63	63
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.03	0.076	-10000	0	-0.47	4	4
MDM2	0.026	0.058	-10000	0	-0.36	1	1
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.096	0.14	-10000	0	-0.42	16	16
STAT5A	-0.013	0.091	-10000	0	-0.43	7	7
ErbB4/EGFR/neuregulin 1 beta	-0.12	0.2	-10000	0	-0.53	53	53
DLG4	0.004	0.069	-10000	0	-0.49	10	10
GRB2/SHC	-0.004	0.037	-10000	0	-0.34	6	6
E4ICDs/TAB2/NCoR1	-0.014	0.049	-10000	0	-0.55	2	2
STAT5A (dimer)	-0.044	0.092	-10000	0	-0.53	6	6
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.007	0.073	-10000	0	-10000	0	0
LRIG1	-0.002	0.099	-10000	0	-0.59	14	14
EREG	-0.013	0.1	-10000	0	-0.49	24	24
BTC	-0.086	0.22	-10000	0	-0.56	88	88
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.016	0.078	-10000	0	-0.38	1	1
ERBB4	0.02	0.064	-10000	0	-0.42	1	1
STAT5B	0.014	0	-10000	0	-10000	0	0
YAP1	-0.036	0.13	-10000	0	-0.59	27	27
GRB2	0.013	0.022	-10000	0	-0.49	1	1
ErbB4/ErbB2/neuregulin 4	-0.007	0.11	-10000	0	-0.48	7	7
glial cell differentiation	0.014	0.048	0.54	2	-10000	0	2
WWOX	0.014	0	-10000	0	-10000	0	0
cell proliferation	-0.1	0.19	-10000	0	-0.55	38	38

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	-0.007	0.1	-10000	0	-0.34	45	45
MAP4K4	-0.022	0.12	-10000	0	-0.46	17	17
BAG4	-0.001	0.095	-10000	0	-0.59	13	13
PKC zeta/ceramide	-0.013	0.074	0.15	6	-0.27	26	32
NFKBIA	0.014	0	-10000	0	-10000	0	0
BIRC3	-0.033	0.16	-10000	0	-0.55	43	43
BAX	0.006	0.026	-10000	0	-10000	0	0
RIPK1	0.014	0	-10000	0	-10000	0	0
AKT1	0.022	0.014	-10000	0	-10000	0	0
BAD	0.003	0.048	0.16	10	-10000	0	10
SMPD1	-0.026	0.089	-10000	0	-0.27	12	12
RB1	0.003	0.051	0.16	10	-0.4	1	11
FADD/Caspase 8	-0.012	0.12	-10000	0	-0.49	13	13
MAP2K4	0.007	0.057	-10000	0	-0.26	8	8
NSMAF	0.014	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.011	0.046	-10000	0	-10000	0	0
EGF	-0.05	0.18	-10000	0	-0.56	58	58
mol:ceramide	-0.006	0.052	0.15	40	-10000	0	40
MADD	0.014	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.007	0.1	-10000	0	-0.34	45	45
ASAH1	0.014	0	-10000	0	-10000	0	0
negative regulation of cell cycle	0.002	0.051	0.16	10	-0.4	1	11
cell proliferation	-0.002	0.093	-10000	0	-0.4	18	18
BID	-0.01	0.091	-10000	0	-0.41	9	9
MAP3K1	0	0.058	0.16	10	-0.27	7	17
EIF2A	0.015	0.052	-10000	0	-0.31	3	3
TRADD	0.013	0.027	-10000	0	-0.59	1	1
CRADD	0.014	0	-10000	0	-10000	0	0
MAPK3	0.022	0.044	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.022	0.044	-10000	0	-10000	0	0
Cathepsin D/ceramide	0.002	0.046	0.16	6	-10000	0	6
FADD	-0.021	0.12	-10000	0	-0.46	17	17
KSR1	0.003	0.048	0.16	10	-10000	0	10
MAPK8	-0.003	0.073	-10000	0	-0.25	25	25
PRKRA	0.003	0.048	0.16	10	-10000	0	10
PDGFA	-0.03	0.14	-10000	0	-0.49	45	45
TRAF2	0.014	0	-10000	0	-10000	0	0
IGF1	-0.008	0.11	-10000	0	-0.56	20	20
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.006	0.052	0.15	40	-10000	0	40
CTSD	0.013	0.022	-10000	0	-0.49	1	1
regulation of nitric oxide biosynthetic process	0	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.001	0.1	-10000	0	-0.43	18	18
PRKCD	-0.018	0.14	-10000	0	-0.59	27	27
PRKCZ	-0.015	0.13	-10000	0	-0.55	27	27
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.007	0.1	-10000	0	-0.34	45	45
RelA/NF kappa B1	0	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	-0.033	0.16	-10000	0	-0.53	45	45
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.032	0.13	-10000	0	-0.5	17	17
TNFR1A/BAG4/TNF-alpha	-0.11	0.17	-10000	0	-0.39	89	89
mol:Sphingosine-1-phosphate	-0.007	0.1	-10000	0	-0.34	45	45
MAP2K1	0.018	0.046	-10000	0	-10000	0	0
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.014	0	-10000	0	-10000	0	0
CYCS	0.008	0.039	0.19	4	-10000	0	4
TNFRSF1A	0.001	0.085	-10000	0	-0.55	12	12
NFKB1	0.014	0	-10000	0	-10000	0	0
TNFR1A/BAG4	-0.02	0.093	-10000	0	-0.44	23	23
EIF2AK2	0.008	0.055	-10000	0	-0.3	5	5
TNF-alpha/TNFR1A/FAN	-0.1	0.15	-10000	0	-0.37	77	77
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	-0.002	0.081	-10000	0	-0.44	3	3
MAP2K2	0.019	0.044	-10000	0	-10000	0	0
SMPD3	-0.047	0.13	-10000	0	-0.37	41	41
TNF	-0.15	0.26	-10000	0	-0.54	156	156
PKC zeta/PAR4	-0.053	0.14	-10000	0	-0.4	68	68
mol:PHOSPHOCHOLINE	0.007	0.077	0.21	48	-10000	0	48
NF kappa B1/RelA/I kappa B alpha	-0.035	0.095	-10000	0	-0.54	4	4
AIFM1	0.008	0.039	0.19	4	-10000	0	4
BCL2	0.005	0.075	-10000	0	-0.59	8	8

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.067	0.14	-10000	0	-0.35	99	99
cell-cell adhesion	0.035	0.099	0.47	14	-10000	0	14
Ephrin B/EPHB2/RasGAP	-0.022	0.08	-10000	0	-0.54	5	5
ITSN1	0.014	0	-10000	0	-10000	0	0
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
SHC1	0.009	0.049	-10000	0	-0.49	5	5
Ephrin B1/EPHB3	-0.003	0.028	-10000	0	-0.29	5	5
Ephrin B1/EPHB1	-0.031	0.1	-10000	0	-0.37	44	44
HRAS/GDP	-0.031	0.094	-10000	0	-0.47	12	12
Ephrin B/EPHB1/GRB7	-0.058	0.14	-10000	0	-0.5	27	27
Endophilin/SYNJ1	0.017	0.088	-10000	0	-0.34	19	19
KRAS	0.013	0.022	-10000	0	-0.49	1	1
Ephrin B/EPHB1/Src	-0.039	0.11	-10000	0	-0.57	11	11
endothelial cell migration	-0.006	0.039	-10000	0	-0.3	4	4
GRB2	0.013	0.022	-10000	0	-0.49	1	1
GRB7	-0.032	0.14	-10000	0	-0.49	43	43
PAK1	-0.007	0.13	-10000	0	-0.47	20	20
HRAS	0.014	0	-10000	0	-10000	0	0
RRAS	0.017	0.088	-10000	0	-0.51	5	5
DNM1	-0.1	0.22	-10000	0	-0.52	112	112
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.001	0.12	-10000	0	-0.54	11	11
lamellipodium assembly	-0.035	0.099	-10000	0	-0.47	14	14
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.007	0.11	-10000	0	-0.5	12	12
PIK3R1	0.014	0	-10000	0	-10000	0	0
EPHB2	0	0.087	-10000	0	-0.52	14	14
EPHB3	0.012	0.031	-10000	0	-0.49	2	2
EPHB1	-0.035	0.17	-10000	0	-0.59	42	42
EPHB4	0.014	0	-10000	0	-10000	0	0
mol:GDP	-0.031	0.091	-10000	0	-0.43	15	15
Ephrin B/EPHB2	-0.022	0.082	-10000	0	-0.37	18	18
Ephrin B/EPHB3	-0.016	0.068	-10000	0	-0.33	14	14
JNK cascade	0.006	0.11	-10000	0	-0.32	45	45
Ephrin B/EPHB1	-0.04	0.12	-10000	0	-0.36	51	51
RAP1/GDP	-0.026	0.078	-10000	0	-0.4	11	11
EFNB2	0.002	0.08	-10000	0	-0.52	12	12
EFNB3	-0.003	0.098	-10000	0	-0.56	15	15
EFNB1	0.011	0.038	-10000	0	-0.49	3	3
Ephrin B2/EPHB1-2	-0.04	0.12	-10000	0	-0.34	61	61
RAP1B	0.013	0.022	-10000	0	-0.49	1	1
RAP1A	0.014	0	-10000	0	-10000	0	0
CDC42/GTP	-0.037	0.11	-10000	0	-0.51	14	14
Rap1/GTP	-0.035	0.1	-10000	0	-0.48	14	14
axon guidance	-0.066	0.14	-10000	0	-0.35	99	99
MAPK3	0.022	0.1	-10000	0	-0.43	13	13
MAPK1	0.022	0.1	-10000	0	-0.43	13	13
Rac1/GDP	0.02	0.099	-10000	0	-0.39	14	14
actin cytoskeleton reorganization	-0.027	0.076	-10000	0	-0.38	12	12
CDC42/GDP	0.02	0.099	-10000	0	-0.42	11	11
PI3K	-0.006	0.039	-10000	0	-0.3	4	4
EFNA5	-0.085	0.22	-10000	0	-0.55	91	91
Ephrin B2/EPHB4	-0.007	0.047	-10000	0	-0.31	12	12
Ephrin B/EPHB2/Intersectin/N-WASP	0.023	0.07	-10000	0	-0.41	5	5
CDC42	0.014	0	-10000	0	-10000	0	0
RAS family/GTP	-0.034	0.097	-10000	0	-0.46	14	14
PTK2	0.009	0.026	-10000	0	-10000	0	0
MAP4K4	0.006	0.11	-10000	0	-0.33	45	45
SRC	0.014	0	-10000	0	-10000	0	0
KALRN	-0.003	0.092	-10000	0	-0.5	17	17
Intersectin/N-WASP	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.018	0.12	-10000	0	-0.42	9	9
MAP2K1	0.015	0.11	-10000	0	-0.46	13	13
WASL	0.014	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.035	0.11	-10000	0	-0.35	45	45
cell migration	0.017	0.12	-10000	0	-0.48	13	13
NRAS	0.014	0	-10000	0	-10000	0	0
SYNJ1	0.017	0.089	-10000	0	-0.35	19	19
PXN	0.014	0	-10000	0	-10000	0	0
TF	-0.011	0.14	-10000	0	-0.55	15	15
HRAS/GTP	-0.038	0.11	-10000	0	-0.51	14	14
Ephrin B1/EPHB1-2	-0.035	0.11	-10000	0	-0.34	54	54
cell adhesion mediated by integrin	0.01	0.067	0.31	15	-10000	0	15
RAC1	0.014	0	-10000	0	-10000	0	0
mol:GTP	-0.041	0.12	-10000	0	-0.55	14	14
RAC1-CDC42/GTP	-0.035	0.1	-10000	0	-0.48	15	15
RASA1	0.014	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.026	0.077	-10000	0	-0.4	10	10
ruffle organization	0.023	0.12	-10000	0	-0.48	14	14
NCK1	0.013	0.027	-10000	0	-0.59	1	1
receptor internalization	-0.033	0.14	-10000	0	-0.58	11	11
Ephrin B/EPHB2/KALRN	-0.029	0.09	-10000	0	-0.53	6	6
ROCK1	0.025	0.027	-10000	0	-0.25	5	5
RAS family/GDP	-0.025	0.072	-10000	0	-0.42	7	7
Rac1/GTP	-0.037	0.11	-10000	0	-0.51	14	14
Ephrin B/EPHB1/Src/Paxillin	0.004	0.11	-10000	0	-0.47	11	11

×

TRAIL signaling pathway

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
TNFSF10	-0.012	0.12	-10000	0	-0.54	25	25
positive regulation of NF-kappaB transcription factor activity	-0.029	0.099	-10000	0	-0.37	40	40
MAP2K4	0.03	0.063	-10000	0	-0.35	3	3
IKBKB	0.014	0	-10000	0	-10000	0	0
TNFRSF10B	0.01	0.051	-10000	0	-0.57	4	4
TNFRSF10A	-0.026	0.15	-10000	0	-0.56	36	36
SMPD1	0.011	0.047	-10000	0	-0.23	13	13
IKBKG	0.014	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	-0.001	0.087	-10000	0	-0.5	15	15
TRAIL/TRAILR2	-0.021	0.092	-10000	0	-0.4	28	28
TRAIL/TRAILR3	-0.041	0.13	-10000	0	-0.41	52	52
TRAIL/TRAILR1	-0.046	0.13	-10000	0	-0.41	58	58
TRAIL/TRAILR4	-0.029	0.1	-10000	0	-0.37	40	40
TRAIL/TRAILR1/DAP3/GTP	-0.035	0.1	-10000	0	-0.31	58	58
IKK complex	-0.01	0.029	-10000	0	-10000	0	0
RIPK1	0.014	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0	0	-10000	0	-10000	0	0
MAPK3	0.005	0.087	-10000	0	-0.38	25	25
MAP3K1	0.024	0.063	-10000	0	-0.34	2	2
TRAILR4 (trimer)	-0.001	0.087	-10000	0	-0.5	15	15
TRADD	0.013	0.027	-10000	0	-0.59	1	1
TRAILR1 (trimer)	-0.026	0.15	-10000	0	-0.56	36	36
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.013	0.081	-10000	0	-0.28	3	3
CFLAR	0.013	0.022	-10000	0	-0.49	1	1
MAPK1	0.005	0.087	-10000	0	-0.38	25	25
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.032	0.09	-10000	0	-0.47	3	3
mol:ceramide	0.011	0.047	-10000	0	-0.23	13	13
FADD	0.014	0	-10000	0	-10000	0	0
MAPK8	0.029	0.082	-10000	0	-0.36	8	8
TRAF2	0.014	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	-0.02	0.13	-10000	0	-0.53	32	32
CHUK	0.014	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.038	0.11	-10000	0	-0.34	58	58
DAP3	0.014	0	-10000	0	-10000	0	0
CASP10	-0.021	0.086	0.27	1	-0.38	14	15
JNK cascade	-0.029	0.099	-10000	0	-0.37	40	40
TRAIL (trimer)	-0.012	0.12	-10000	0	-0.53	25	25
TNFRSF10C	-0.02	0.13	-10000	0	-0.53	32	32
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.032	0.092	-10000	0	-0.31	38	38
TRAIL/TRAILR2/FADD	-0.018	0.077	-10000	0	-0.33	28	28
cell death	0.011	0.047	-10000	0	-0.23	13	13
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.028	0.057	-10000	0	-0.52	1	1
TRAILR2 (trimer)	0.01	0.051	-10000	0	-0.57	4	4
CASP8	-0.003	0.049	-10000	0	-0.8	1	1
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.015	0.063	-10000	0	-0.6	1	1

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.007	0.091	-9999	-0.32	37	37
SNTA1	-0.026	0.15	-9999	-0.57	36	36
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.006	0.094	-9999	-0.32	39	39
MAPK12	0.027	0.044	-9999	-0.33	6	6
CCND1	0.008	0.069	-9999	-0.39	12	12
p38 gamma/SNTA1	0.011	0.09	-9999	-0.3	34	34
MAP2K3	0.011	0.038	-9999	-0.49	3	3
PKN1	0.014	0	-9999	-10000	0	0
G2/M transition checkpoint	0.026	0.044	-9999	-0.33	6	6
MAP2K6	0.022	0.031	-9999	-0.32	2	2
MAPT	0.011	0.084	-9999	-0.31	25	25
MAPK13	-0.004	0.11	-9999	-0.38	37	37
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.015	0.031	-9999	-0.22	9	9

×

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

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
BAG4	-0.001	0.095	-9999	-0.59	13	13
Caspase 8 (4 units)	-0.011	0.082	-9999	-0.36	15	15
NEF	-0.004	0.03	-9999	-10000	0	0
NFKBIA	0.009	0.029	-9999	-10000	0	0
BIRC3	0	0.16	-9999	-0.54	43	43
CYCS	0.024	0.084	-9999	-0.32	12	12
RIPK1	0.014	0	-9999	-10000	0	0
CD247	-0.024	0.15	-9999	-0.6	31	31
MAP2K7	0.017	0.074	-9999	-0.31	4	4
protein ubiquitination	0.017	0.093	-9999	-0.4	7	7
CRADD	0.014	0	-9999	-10000	0	0
DAXX	0.014	0	-9999	-10000	0	0
FAS	-0.005	0.1	-9999	-0.54	18	18
BID	0.016	0.087	-9999	-0.33	15	15
NF-kappa-B/RelA/I kappa B alpha	-0.021	0.071	-9999	-10000	0	0
TRADD	0.013	0.027	-9999	-0.59	1	1
MAP3K5	0.006	0.07	-9999	-0.59	7	7
CFLAR	0.013	0.022	-9999	-0.49	1	1
FADD	0.014	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.021	0.071	-9999	-10000	0	0
MAPK8	0.017	0.085	-9999	-0.51	1	1
APAF1	0.014	0	-9999	-10000	0	0
TRAF1	0.004	0.078	-9999	-0.58	9	9
TRAF2	0.014	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.009	0.09	-9999	-0.29	29	29
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	-0.001	0.11	-9999	-0.53	8	8
CHUK	0.016	0.099	-9999	-0.44	7	7
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.02	0.072	-9999	-0.31	19	19
TCRz/NEF	-0.038	0.13	-9999	-0.42	46	46
TNF	-0.15	0.26	-9999	-0.54	156	156
FASLG	-0.026	0.17	-9999	-0.56	41	41
NFKB1	0.009	0.029	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.11	0.17	-9999	-0.39	89	89
CASP6	-0.019	0.067	-9999	-0.58	3	3
CASP7	0.032	0.16	-9999	-0.51	33	33
RELA	0.009	0.029	-9999	-10000	0	0
CASP2	0.014	0	-9999	-10000	0	0
CASP3	0.032	0.16	-9999	-0.51	33	33
TNFRSF1A	0.001	0.085	-9999	-0.55	12	12
TNFR1A/BAG4	-0.02	0.093	-9999	-0.44	23	23
CASP8	-0.002	0.089	-9999	-0.5	16	16
CASP9	0.013	0.022	-9999	-0.49	1	1
MAP3K14	0.008	0.11	-9999	-0.5	7	7
APAF-1/Caspase 9	-0.038	0.11	-9999	-0.4	35	35
BCL2	0.019	0.089	-9999	-0.48	2	2

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.13	0.38	-9999	-1.1	58	58
RAD9A	0.014	0	-9999	-10000	0	0
AP1	-0.068	0.18	-9999	-0.42	102	102
IFNAR2	0.013	0.006	-9999	-10000	0	0
AKT1	0.001	0.049	-9999	-0.28	2	2
ER alpha/Oestrogen	-0.011	0.089	-9999	-0.4	26	26
NFX1/SIN3/HDAC complex	0.04	0.032	-9999	-10000	0	0
EGF	-0.051	0.18	-9999	-0.56	58	58
SMG5	0.013	0.022	-9999	-0.49	1	1
SMG6	0.014	0	-9999	-10000	0	0
SP3/HDAC2	0.019	0.012	-9999	-10000	0	0
TERT/c-Abl	-0.13	0.34	-9999	-1	58	58
SAP18	0.013	0.004	-9999	-10000	0	0
MRN complex	-0.001	0.016	-9999	-0.36	1	1
WT1	-0.038	0.14	-9999	-0.49	45	45
WRN	0.009	0.053	-9999	-0.59	4	4
SP1	0.013	0.009	-9999	-10000	0	0
SP3	0.012	0.006	-9999	-10000	0	0
TERF2IP	0.014	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.13	0.29	-9999	-0.9	58	58
Mad/Max	0.019	0.009	-9999	-10000	0	0
TERT	-0.14	0.4	-9999	-1.2	58	58
CCND1	-0.12	0.36	-9999	-1	66	66
MAX	0.012	0.006	-9999	-10000	0	0
RBBP7	0.013	0.004	-9999	-10000	0	0
RBBP4	0.012	0.027	-9999	-0.6	1	1
TERF2	0	0	-9999	-10000	0	0
PTGES3	0.014	0	-9999	-10000	0	0
SIN3A	0.013	0.004	-9999	-10000	0	0
Telomerase/911	0.032	0.039	-9999	-10000	0	0
CDKN1B	0.012	0.076	-9999	-0.53	2	2
RAD1	0.014	0	-9999	-10000	0	0
XRCC5	0.014	0	-9999	-10000	0	0
XRCC6	0.014	0	-9999	-10000	0	0
SAP30	0.012	0.027	-9999	-0.59	1	1
TRF2/PARP2	0	0	-9999	-10000	0	0
UBE3A	0.012	0.005	-9999	-10000	0	0
JUN	0.002	0.074	-9999	-0.5	11	11
E6	-0.001	0.005	-9999	-10000	0	0
HPV-16 E6/E6AP	0.009	0.007	-9999	-10000	0	0
FOS	-0.097	0.22	-9999	-0.55	101	101
IFN-gamma/IRF1	-0.011	0.087	-9999	-0.35	30	30
PARP2	0.014	0	-9999	-10000	0	0
BLM	-0.051	0.18	-9999	-0.53	62	62
Telomerase	-0.037	0.1	-9999	-0.39	31	31
IRF1	-0.009	0.11	-9999	-0.48	27	27
ESR1	-0.015	0.12	-9999	-0.54	26	26
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	0.022	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.045	0.033	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.045	0.034	-9999	-10000	0	0
HDAC1	0.008	0.053	-9999	-0.59	4	4
HDAC2	0.012	0.009	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.019	0.059	-9999	-0.42	9	9
ABL1	0.014	0	-9999	-10000	0	0
MXD1	0.012	0.006	-9999	-10000	0	0
MRE11A	0.014	0	-9999	-10000	0	0
HUS1	0.013	0.022	-9999	-0.49	1	1
RPS6KB1	0.014	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.14	0.32	-9999	-1	57	57
NR2F2	-0.009	0.12	-9999	-0.51	25	25
MAPK3	0.011	0.008	-9999	-10000	0	0
MAPK1	0.011	0.008	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.004	0.079	-9999	-0.59	9	9
NFKB1	0.014	0	-9999	-10000	0	0
HNRNPC	0.014	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0	0	-9999	-10000	0	0
NBN	0.014	0	-9999	-10000	0	0
EGFR	-0.084	0.21	-9999	-0.55	89	89
mol:Oestrogen	-0.001	0.003	-9999	-10000	0	0
EGF/EGFR	-0.097	0.2	-9999	-0.44	132	132
MYC	-0.017	0.13	-9999	-0.58	26	26
IL2	-0.003	0.014	-9999	-10000	0	0
KU	0	0	-9999	-10000	0	0
RAD50	0.013	0.027	-9999	-0.59	1	1
HSP90AA1	0.014	0	-9999	-10000	0	0
TGFB1	0.004	0.079	-9999	-0.59	9	9
TRF2/BLM	-0.042	0.11	-9999	-0.35	62	62
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.11	0.35	-9999	-1	58	58
SP1/HDAC2	0.019	0.017	-9999	-10000	0	0
PINX1	0.014	0	-9999	-10000	0	0
Telomerase/EST1A	-0.13	0.29	-9999	-0.9	58	58
Smad3/Myc	0.005	0.098	-9999	-0.36	34	34
911 complex	-0.001	0.012	-9999	-0.28	1	1
IFNG	0.003	0.049	-9999	-0.49	5	5
Telomerase/PinX1	-0.13	0.29	-9999	-0.9	58	58
Telomerase/AKT1/mTOR/p70S6K	0.009	0.074	-9999	-10000	0	0
SIN3B	0.013	0.004	-9999	-10000	0	0
YWHAE	0.014	0	-9999	-10000	0	0
Telomerase/EST1B	-0.13	0.29	-9999	-0.91	58	58
response to DNA damage stimulus	0.004	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	-0.001	0.012	-9999	-10000	0	0
TRF2/WRN	-0.003	0.035	-9999	-0.4	4	4
Telomerase/hnRNP C1/C2	-0.13	0.29	-9999	-0.9	58	58
E2F1	-0.016	0.12	-9999	-0.52	28	28
ZNFX1	0.013	0.004	-9999	-10000	0	0
PIF1	-0.052	0.18	-9999	-0.54	62	62
NCL	0.014	0	-9999	-10000	0	0
DKC1	0.014	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

S1P4 pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	0.008	0.059	-9999	-0.59	5	5
CDC42/GTP	-0.012	0.049	-9999	-0.39	3	3
PLCG1	0.03	0.061	-9999	-0.4	3	3
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.014	0	-9999	-10000	0	0
GNAI3	0.014	0	-9999	-10000	0	0
G12/G13	-0.001	0.019	-9999	-0.43	1	1
cell migration	-0.011	0.048	-9999	-0.38	3	3
S1PR5	-0.13	0.25	-9999	-0.55	134	134
S1PR4	0	0.086	-9999	-0.51	14	14
MAPK3	0.03	0.061	-9999	-0.4	3	3
MAPK1	0.03	0.061	-9999	-0.4	3	3
S1P/S1P5/Gi	-0.034	0.13	-9999	-0.28	80	80
GNAI1	-0.005	0.1	-9999	-0.59	16	16
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.087	0.15	-9999	-0.34	134	134
RHOA	0.026	0.047	-9999	-0.3	4	4
S1P/S1P4/Gi	0.023	0.064	-9999	-0.43	3	3
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	0.014	0	-9999	-10000	0	0
S1P/S1P4/G12/G13	-0.008	0.046	-9999	-0.33	4	4
GNA12	0.013	0.027	-9999	-0.59	1	1
GNA13	0.014	0	-9999	-10000	0	0
CDC42	0.014	0	-9999	-10000	0	0

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	-0.034	0.093	0.18	3	-0.4	18	21
CaM/Ca2+	-0.002	0.025	-10000	0	-0.4	2	2
AKT1	0.014	0	-10000	0	-10000	0	0
AKT2	0.014	0	-10000	0	-10000	0	0
STXBP4	0.013	0.027	-10000	0	-0.59	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.027	0.14	0.25	63	-0.46	16	79
YWHAZ	0.014	0	-10000	0	-10000	0	0
CALM1	0.012	0.035	-10000	0	-0.54	2	2
YWHAQ	0.014	0	-10000	0	-10000	0	0
TBC1D4	0.025	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	-0.01	0.11	-10000	0	-0.49	25	25
YWHAB	0.014	0	-10000	0	-10000	0	0
SNARE/Synip	-0.001	0.016	-10000	0	-0.36	1	1
YWHAG	0.002	0.079	-10000	0	-0.49	13	13
ASIP	-0.096	0.22	-10000	0	-0.55	99	99
PRKCI	0.014	0	-10000	0	-10000	0	0
AS160/CaM/Ca2+	-0.002	0.025	-10000	0	-0.4	2	2
RHOQ	0.014	0	-10000	0	-10000	0	0
GYS1	0.034	0.014	-10000	0	-0.29	1	1
PRKCZ	-0.015	0.13	-10000	0	-0.55	27	27
TRIP10	0.007	0.065	-10000	0	-0.55	7	7
TC10/GTP/CIP4/Exocyst	-0.005	0.039	-10000	0	-0.33	7	7
AS160/14-3-3	0.003	0.087	-10000	0	-0.37	3	3
VAMP2	0.014	0	-10000	0	-10000	0	0
SLC2A4	0.025	0.15	0.25	63	-0.52	16	79
STX4	0.014	0	-10000	0	-10000	0	0
GSK3B	0.028	0.016	-10000	0	-0.34	1	1
SFN	-0.11	0.23	-10000	0	-0.53	119	119
LNPEP	-0.012	0.12	-10000	0	-0.59	22	22
YWHAE	0.014	0	-10000	0	-10000	0	0

×

Plasma membrane estrogen receptor signaling

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
GNB1/GNG2	-0.025	0.082	-10000	0	-0.31	31	31
ER alpha/Gai/GDP/Gbeta gamma	0.026	0.088	-10000	0	-0.37	18	18
AKT1	0.017	0.12	-10000	0	-0.72	13	13
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	0.015	0.12	-10000	0	-0.73	13	13
mol:Ca2+	-0.008	0.14	-10000	0	-0.49	25	25
IGF1R	0.013	0.022	-10000	0	-0.49	1	1
E2/ER alpha (dimer)/Striatin	-0.035	0.11	-10000	0	-0.35	51	51
SHC1	0.009	0.049	-10000	0	-0.49	5	5
apoptosis	-0.017	0.12	0.69	13	-10000	0	13
RhoA/GTP	-0.011	0.049	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.02	0.074	-10000	0	-0.38	17	17
regulation of stress fiber formation	-0.015	0.099	0.4	9	-10000	0	9
E2/ERA-ERB (dimer)	-0.028	0.097	-10000	0	-0.35	42	42
KRAS	0.013	0.022	-10000	0	-0.49	1	1
G13/GTP	-0.015	0.065	-10000	0	-0.29	26	26
pseudopodium formation	0.015	0.099	-10000	0	-0.4	9	9
E2/ER alpha (dimer)/PELP1	-0.016	0.071	-10000	0	-0.32	26	26
GRB2	0.013	0.022	-10000	0	-0.49	1	1
GNG2	0.009	0.053	-10000	0	-0.59	4	4
GNAO1	0.008	0.059	-10000	0	-0.59	5	5
HRAS	0.014	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.027	0.096	-10000	0	-0.43	13	13
E2/ER beta (dimer)	-0.014	0.076	-10000	0	-0.41	18	18
mol:GDP	-0.024	0.083	-10000	0	-0.35	27	27
mol:NADP	0.027	0.096	-10000	0	-0.43	13	13
PIK3R1	0.014	0	-10000	0	-10000	0	0
mol:IP3	-0.01	0.14	-10000	0	-0.52	25	25
IGF-1R heterotetramer	0.013	0.022	-10000	0	-0.49	1	1
PLCB1	-0.007	0.13	-10000	0	-0.49	21	21
PLCB2	-0.007	0.14	-10000	0	-0.53	23	23
IGF1	-0.008	0.11	-10000	0	-0.56	20	20
mol:L-citrulline	0.027	0.096	-10000	0	-0.43	13	13
RHOA	0.014	0	-10000	0	-10000	0	0
Gai/GDP	-0.013	0.077	-10000	0	-0.7	5	5
JNK cascade	-0.014	0.076	-10000	0	-0.41	18	18
BCAR1	0.013	0.027	-10000	0	-0.59	1	1
ESR2	-0.006	0.11	-10000	0	-0.56	18	18
GNAQ	0.014	0	-10000	0	-10000	0	0
ESR1	-0.014	0.12	-10000	0	-0.54	26	26
Gq family/GDP/Gbeta gamma	0.01	0.12	-10000	0	-0.45	24	24
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.032	0.054	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.021	0.078	-10000	0	-0.41	17	17
GNAZ	0.014	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)	-0.02	0.086	-10000	0	-0.39	26	26
STRN	-0.016	0.13	-10000	0	-0.59	26	26
GNAL	-0.058	0.2	-10000	0	-0.59	62	62
PELP1	0.014	0	-10000	0	-10000	0	0
MAPK11	0.001	0.083	-10000	0	-0.35	27	27
GNAI2	0.014	0	-10000	0	-10000	0	0
GNAI3	0.014	0	-10000	0	-10000	0	0
GNAI1	-0.005	0.1	-10000	0	-0.59	16	16
HBEGF	-0.004	0.12	-10000	0	-0.36	21	21
cAMP biosynthetic process	-0.057	0.12	-10000	0	-0.3	97	97
SRC	0.033	0.084	-10000	0	-0.35	16	16
PI3K	-0.001	0.019	-10000	0	-0.43	1	1
GNB1	0.014	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.022	0.074	-10000	0	-0.34	14	14
SOS1	0.014	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.024	0.074	-10000	0	-0.34	19	19
Gs family/GTP	-0.058	0.12	-10000	0	-0.31	97	97
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0	0.011	-10000	0	-0.25	1	1
vasodilation	0.027	0.093	-10000	0	-0.42	13	13
mol:DAG	-0.01	0.14	-10000	0	-0.52	25	25
Gs family/GDP/Gbeta gamma	-0.047	0.1	-10000	0	-0.37	23	23
MSN	0.014	0.1	-10000	0	-0.43	9	9
Gq family/GTP	-0.005	0.12	-10000	0	-0.5	19	19
mol:PI-3-4-5-P3	0.016	0.12	-10000	0	-0.7	13	13
NRAS	0.014	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.027	0.093	0.42	13	-10000	0	13
GRB2/SOS1	-0.001	0.015	-10000	0	-0.34	1	1
RhoA/GDP	-0.022	0.077	-10000	0	-0.33	27	27
NOS3	0.026	0.099	-10000	0	-0.45	13	13
GNA11	0.004	0.079	-10000	0	-0.59	9	9
MAPKKK cascade	0.023	0.13	-10000	0	-0.4	37	37
E2/ER alpha (dimer)/PELP1/Src	-0.021	0.076	-10000	0	-0.41	16	16
ruffle organization	0.015	0.099	-10000	0	-0.4	9	9
ROCK2	0.027	0.083	-10000	0	-0.51	2	2
GNA14	-0.014	0.12	-10000	0	-0.56	25	25
GNA15	-0.007	0.11	-10000	0	-0.57	19	19
GNA13	0.014	0	-10000	0	-10000	0	0
MMP9	-0.032	0.14	-10000	0	-0.37	33	33
MMP2	0.027	0.1	-10000	0	-0.36	18	18

×

BARD1 signaling events

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
BARD1/CSTF1	-0.025	0.1	-10000	0	-0.42	31	31
ATM	0.014	0	-10000	0	-10000	0	0
UBE2D3	0.014	0	-10000	0	-10000	0	0
PRKDC	0.014	0	-10000	0	-10000	0	0
ATR	0.014	0	-10000	0	-10000	0	0
UBE2L3	0.014	0	-10000	0	-10000	0	0
FANCD2	0.015	0.057	-10000	0	-0.34	6	6
protein ubiquitination	-0.026	0.093	-10000	0	-0.58	5	5
XRCC5	0.014	0	-10000	0	-10000	0	0
XRCC6	0.014	0	-10000	0	-10000	0	0
M/R/N Complex	-0.001	0.016	-10000	0	-0.36	1	1
MRE11A	0.014	0	-10000	0	-10000	0	0
DNA-PK	0	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	-0.013	0.054	-10000	0	-0.38	7	7
FANCF	0.014	0	-10000	0	-10000	0	0
BRCA1	0.01	0.044	-10000	0	-0.49	4	4
CCNE1	0.011	0.038	-10000	0	-0.49	3	3
CDK2/Cyclin E1	-0.011	0.067	-10000	0	-0.39	15	15
FANCG	0.013	0.022	-10000	0	-0.49	1	1
BRCA1/BACH1/BARD1	-0.028	0.11	-10000	0	-0.42	34	34
FANCE	0.014	0	-10000	0	-10000	0	0
FANCC	0.011	0.041	-10000	0	-0.52	3	3
NBN	0.014	0	-10000	0	-10000	0	0
FANCA	-0.027	0.14	-10000	0	-0.51	40	40
DNA repair	0.017	0.15	-10000	0	-0.51	16	16
BRCA1/BARD1/ubiquitin	-0.028	0.11	-10000	0	-0.42	34	34
BARD1/DNA-PK	-0.019	0.074	-10000	0	-0.32	29	29
FANCL	0.014	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.025	0.1	0.42	31	-10000	0	31
BRCA1/BARD1/CTIP/M/R/N Complex	0.025	0.075	-10000	0	-0.47	3	3
BRCA1/BACH1/BARD1/TopBP1	-0.024	0.092	-10000	0	-0.36	34	34
BRCA1/BARD1/P53	-0.03	0.097	-10000	0	-0.34	42	42
BARD1/CSTF1/BRCA1	-0.023	0.089	-10000	0	-0.35	34	34
BRCA1/BACH1	0.01	0.044	-10000	0	-0.49	4	4
BARD1	-0.022	0.14	-10000	0	-0.59	31	31
PCNA	0.012	0.031	-10000	0	-0.49	2	2
BRCA1/BARD1/UbcH5C	-0.023	0.089	-10000	0	-0.35	34	34
BRCA1/BARD1/UbcH7	-0.023	0.089	-10000	0	-0.35	34	34
BRCA1/BARD1/RAD51/PCNA	-0.053	0.12	-10000	0	-0.38	45	45
BARD1/DNA-PK/P53	-0.026	0.086	-10000	0	-0.6	2	2
BRCA1/BARD1/Ubiquitin	-0.028	0.11	-10000	0	-0.42	34	34
BRCA1/BARD1/CTIP	0.012	0.094	-10000	0	-0.34	30	30
FA complex	0.028	0.057	-10000	0	-0.25	1	1
BARD1/EWS	-0.025	0.1	-10000	0	-0.42	31	31
RBBP8	0.023	0.028	-10000	0	-0.34	3	3
TP53	-0.003	0.1	-10000	0	-0.59	15	15
TOPBP1	0.013	0.027	-10000	0	-0.59	1	1
G1/S transition of mitotic cell cycle	0.03	0.096	0.34	42	-10000	0	42
BRCA1/BARD1	-0.027	0.094	-10000	0	-0.59	5	5
CSTF1	0.014	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.026	0.1	-10000	0	-0.43	31	31
CDK2	0	0.086	-10000	0	-0.53	13	13
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.048	0.17	-10000	0	-0.51	61	61
RAD50	0.013	0.027	-10000	0	-0.59	1	1
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.028	0.11	-10000	0	-0.42	34	34
EWSR1	0.014	0	-10000	0	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.013	0.022	-10000	0	-0.49	1	1
Rac1/GDP	0.006	0.017	-10000	0	-10000	0	0
DOCK1	0.009	0.053	-10000	0	-0.59	4	4
ITGA4	-0.052	0.18	-10000	0	-0.53	62	62
RAC1	0.014	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	-0.077	0.17	-10000	0	-0.43	93	93
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.014	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	-0.039	0.11	-10000	0	-0.32	62	62
alpha4/beta7 Integrin/Paxillin	-0.028	0.14	-10000	0	-0.37	57	57
lamellipodium assembly	0.004	0.038	-10000	0	-0.37	1	1
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
PI3K	-0.001	0.019	-10000	0	-0.43	1	1
ARF6	0.014	0	-10000	0	-10000	0	0
TLN1	0.014	0	-10000	0	-10000	0	0
PXN	0.025	0	-10000	0	-10000	0	0
PIK3R1	0.014	0	-10000	0	-10000	0	0
ARF6/GTP	-0.028	0.077	-10000	0	-0.43	2	2
cell adhesion	-0.031	0.085	-10000	0	-0.46	2	2
CRKL/CBL	-0.001	0.015	-10000	0	-0.34	1	1
alpha4/beta1 Integrin/Paxillin	-0.002	0.1	-10000	0	-0.33	28	28
ITGB1	0.012	0.031	-10000	0	-0.49	2	2
ITGB7	-0.034	0.16	-10000	0	-0.54	45	45
ARF6/GDP	0.006	0.017	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.074	0.17	-10000	0	-0.54	15	15
p130Cas/Crk/Dock1	-0.003	0.035	-10000	0	-0.36	5	5
VCAM1	-0.14	0.25	-10000	0	-0.56	134	134
alpha4/beta1 Integrin/Paxillin/Talin	0.007	0.1	-10000	0	-0.47	2	2
alpha4/beta1 Integrin/Paxillin/GIT1	0.007	0.1	-10000	0	-0.47	2	2
BCAR1	0.013	0.027	-10000	0	-0.59	1	1
mol:GDP	0.031	0.085	0.46	2	-10000	0	2
CBL	0.014	0	-10000	0	-10000	0	0
PRKACA	0.014	0	-10000	0	-10000	0	0
GIT1	0.014	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.007	0.1	-10000	0	-0.47	2	2
Rac1/GTP	0.004	0.041	-10000	0	-0.41	1	1

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.014	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.013	0.027	-9999	-0.59	1	1
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.012	0.031	-9999	-0.49	2	2
RAC1-CDC42/GTP/PAK family	-0.032	0.1	-9999	-0.22	106	106
response to UV	0	0	-9999	-10000	0	0
YES1	0.009	0.053	-9999	-0.59	4	4
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.014	0	-9999	-10000	0	0
FYN	0.014	0	-9999	-10000	0	0
MAP3K12	0.014	0	-9999	-10000	0	0
FGR	0.011	0.038	-9999	-0.49	3	3
p38 alpha/TAB1	-0.025	0.057	-9999	-0.32	8	8
PRKG1	-0.039	0.17	-9999	-0.58	46	46
DUSP8	0.001	0.083	-9999	-0.53	12	12
PGK/cGMP/p38 alpha	-0.044	0.09	-9999	-0.3	38	38
apoptosis	-0.024	0.055	-9999	-0.31	8	8
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0.004	0.073	-9999	-0.51	10	10
DUSP1	-0.02	0.13	-9999	-0.53	32	32
PAK1	-0.035	0.15	-9999	-0.5	49	49
SRC	0.014	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.002	0.021	-9999	-10000	0	0
TRAF6	0.013	0.027	-9999	-0.59	1	1
RAC1	0.014	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0.013	0.022	-9999	-0.49	1	1
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	-0.004	0.1	-9999	-0.38	13	13
BLK	-0.1	0.22	-9999	-0.52	113	113
HCK	-0.007	0.11	-9999	-0.54	20	20
MAP2K3	0.011	0.038	-9999	-0.49	3	3
DUSP16	0.014	0	-9999	-10000	0	0
DUSP10	-0.004	0.1	-9999	-0.55	17	17
TRAF6/MEKK3	-0.001	0.015	-9999	-0.33	1	1
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.008	0.081	-9999	-0.33	9	9
positive regulation of innate immune response	0.001	0.11	-9999	-0.42	11	11
LCK	-0.081	0.21	-9999	-0.54	89	89
p38alpha-beta/MKP7	0.008	0.1	-9999	-0.43	8	8
p38alpha-beta/MKP5	0	0.11	-9999	-0.43	12	12
PGK/cGMP	-0.038	0.12	-9999	-0.42	46	46
PAK2	0.014	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.007	0.12	-9999	-0.42	13	13
CDC42	0.014	0	-9999	-10000	0	0
RALB	0.014	0	-9999	-10000	0	0
RALA	0.014	0	-9999	-10000	0	0
PAK3	-0.11	0.24	-9999	-0.56	115	115

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.099	0.23	-9999	-0.55	103	103
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.014	0	-9999	-10000	0	0
TCEB1	0.014	0	-9999	-10000	0	0
HIF1A/p53	0.021	0.056	-9999	-0.27	14	14
HIF1A	0.023	0.025	-9999	-0.24	1	1
COPS5	0.014	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0	0	-9999	-10000	0	0
FIH (dimer)	0.014	0	-9999	-10000	0	0
CDKN2A	-0.1	0.23	-9999	-0.56	104	104
ARNT/IPAS	-0.08	0.16	-9999	-0.4	104	104
HIF1AN	0.014	0	-9999	-10000	0	0
GNB2L1	0.014	0	-9999	-10000	0	0
HIF1A/ARNT	0.03	0.028	-9999	-0.3	1	1
CUL2	0.014	0	-9999	-10000	0	0
OS9	0.003	0.073	-9999	-0.49	11	11
RACK1/Elongin B/Elongin C	0	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.03	0.024	-9999	-10000	0	0
PHD1-3/OS9	-0.013	0.06	-9999	-0.32	13	13
HIF1A/RACK1/Elongin B/Elongin C	-0.002	0.014	-9999	-10000	0	0
VHL	0.014	0	-9999	-10000	0	0
HSP90AA1	0.014	0	-9999	-10000	0	0
HIF1A/JAB1	0.03	0.024	-9999	-10000	0	0
EGLN3	-0.001	0.095	-9999	-0.59	13	13
EGLN2	0.014	0	-9999	-10000	0	0
EGLN1	0.014	0	-9999	-10000	0	0
TP53	-0.003	0.1	-9999	-0.59	15	15
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.041	0.006	-9999	-10000	0	0
ARNT	0.013	0.022	-9999	-0.49	1	1
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.014	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.028	0.12	-9999	-0.28	84	84

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.019	0.066	-10000	0	-0.38	2	2
adherens junction organization	-0.03	0.12	-10000	0	-0.37	24	24
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.019	0.12	-10000	0	-0.42	8	8
FMN1	-0.06	0.15	-10000	0	-0.5	24	24
mol:IP3	0.01	0.067	-10000	0	-0.4	2	2
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.015	0.11	-10000	0	-0.55	3	3
CTNNB1	0.016	0.004	-10000	0	-10000	0	0
AKT1	0.013	0.076	-10000	0	-0.43	2	2
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.03	0.15	-10000	0	-0.41	61	61
CTNND1	0.014	0.002	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.006	0.1	-10000	0	-0.5	3	3
VASP	-0.007	0.1	-10000	0	-0.52	3	3
ZYX	-0.011	0.11	-10000	0	-0.5	4	4
JUB	-0.02	0.12	-10000	0	-0.51	9	9
EGFR(dimer)	-0.055	0.15	-10000	0	-0.43	26	26
E-cadherin/beta catenin-gamma catenin	-0.081	0.14	-10000	0	-0.32	132	132
mol:PI-3-4-5-P3	-0.03	0.061	-10000	0	-0.41	3	3
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
PI3K	-0.03	0.062	-10000	0	-0.41	3	3
FYN	0.021	0.066	-10000	0	-0.32	2	2
mol:Ca2+	0.01	0.066	-10000	0	-0.39	2	2
JUP	0.005	0.081	-10000	0	-0.57	10	10
PIK3R1	0.015	0.001	-10000	0	-10000	0	0
mol:DAG	0.01	0.067	-10000	0	-0.4	2	2
CDH1	-0.12	0.24	-10000	0	-0.54	125	125
RhoA/GDP	-0.019	0.12	-10000	0	-0.42	8	8
establishment of polarity of embryonic epithelium	-0.006	0.1	-10000	0	-0.5	3	3
SRC	0.014	0	-10000	0	-10000	0	0
RAC1	0.014	0	-10000	0	-10000	0	0
RHOA	0.014	0	-10000	0	-10000	0	0
EGFR	-0.083	0.21	-10000	0	-0.55	89	89
CASR	0.009	0.073	-10000	0	-0.36	2	2
RhoA/GTP	-0.02	0.042	-10000	0	-0.35	2	2
AKT2	0.013	0.076	-10000	0	-0.43	2	2
actin cable formation	-0.051	0.15	-10000	0	-0.48	25	25
apoptosis	0.026	0.054	0.42	2	-10000	0	2
CTNNA1	0.014	0.002	-10000	0	-10000	0	0
mol:GDP	-0.029	0.12	-10000	0	-0.4	17	17
PIP5K1A	-0.006	0.1	-10000	0	-0.52	3	3
PLCG1	0.01	0.068	-10000	0	-0.41	2	2
Rac1/GTP	-0.076	0.12	-10000	0	-0.39	26	26
homophilic cell adhesion	0.001	0.002	-10000	0	-10000	0	0

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.021	0.04	-9999	-0.43	4	4
SMARCC1	0.009	0.013	-9999	-10000	0	0
REL	-0.017	0.13	-9999	-0.56	29	29
HDAC7	0.021	0.1	-9999	-0.42	5	5
JUN	0.002	0.074	-9999	-0.5	11	11
EP300	0.009	0.053	-9999	-0.59	4	4
KAT2B	0.013	0.022	-9999	-0.49	1	1
KAT5	0.014	0	-9999	-10000	0	0
MAPK14	0.023	0.023	-9999	-0.42	1	1
FOXO1	0.011	0.044	-9999	-0.56	3	3
T-DHT/AR	0.017	0.11	-9999	-0.43	7	7
MAP2K6	0.012	0.027	-9999	-0.59	1	1
BRM/BAF57	0.004	0.021	-9999	-0.43	1	1
MAP2K4	0.012	0.032	-9999	-0.5	2	2
SMARCA2	0.012	0.027	-9999	-0.59	1	1
PDE9A	-0.022	0.1	-9999	-1	3	3
NCOA2	-0.028	0.15	-9999	-0.59	35	35
CEBPA	-0.016	0.13	-9999	-0.56	27	27
EHMT2	0.013	0.004	-9999	-10000	0	0
cell proliferation	0.031	0.12	-9999	-0.44	11	11
NR0B1	-0.099	0.23	-9999	-0.55	103	103
EGR1	-0.11	0.23	-9999	-0.54	114	114
RXRs/9cRA	-0.035	0.11	-9999	-0.32	65	65
AR/RACK1/Src	-0.011	0.079	-9999	-0.39	9	9
AR/GR	-0.015	0.12	-9999	-0.4	16	16
GNB2L1	0.014	0.001	-9999	-10000	0	0
PKN1	0.014	0	-9999	-10000	0	0
RCHY1	0.014	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0.002	-9999	-10000	0	0
MAPK8	0.01	0.078	-9999	-0.42	16	16
T-DHT/AR/TIF2/CARM1	-0.002	0.14	-9999	-0.54	21	21
SRC	0.028	0.064	-9999	-0.3	3	3
NR3C1	0.014	0	-9999	-10000	0	0
KLK3	-0.045	0.14	-9999	-0.52	8	8
APPBP2	0.014	0.005	-9999	-10000	0	0
TRIM24	0.012	0.022	-9999	-0.49	1	1
T-DHT/AR/TIP60	0.012	0.086	-9999	-0.44	7	7
TMPRSS2	-0.13	0.32	-9999	-1.1	45	45
RXRG	-0.061	0.2	-9999	-0.58	65	65
mol:9cRA	0	0.001	-9999	-10000	0	0
RXRA	0.014	0.001	-9999	-10000	0	0
RXRB	0.014	0.001	-9999	-10000	0	0
CARM1	0.014	0.001	-9999	-10000	0	0
NR2C2	0.002	0.084	-9999	-0.59	10	10
KLK2	-0.008	0.15	-9999	-0.44	32	32
AR	-0.023	0.13	-9999	-0.3	72	72
SENP1	0.014	0.001	-9999	-10000	0	0
HSP90AA1	0.014	0	-9999	-10000	0	0
MDM2	0.013	0.032	-9999	-0.49	2	2
SRY	-0.021	0.11	-9999	-0.49	27	27
GATA2	-0.004	0.1	-9999	-0.56	16	16
MYST2	0.014	0.001	-9999	-10000	0	0
HOXB13	-0.053	0.16	-9999	-0.5	60	60
T-DHT/AR/RACK1/Src	0.018	0.086	-9999	-0.4	9	9
positive regulation of transcription	-0.004	0.1	-9999	-0.56	16	16
DNAJA1	0.014	0.005	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.03	0.026	-9999	-0.24	4	4
NCOA1	0.017	0.005	-9999	-10000	0	0
SPDEF	-0.044	0.17	-9999	-0.54	53	53
T-DHT/AR/TIF2	0.015	0.12	-9999	-0.58	13	13
T-DHT/AR/Hsp90	0.012	0.086	-9999	-0.41	9	9
GSK3B	0.013	0.027	-9999	-0.59	1	1
NR2C1	0.014	0.001	-9999	-10000	0	0
mol:T-DHT	0.023	0.068	-9999	-0.32	16	16
SIRT1	0.014	0	-9999	-10000	0	0
ZMIZ2	0.015	0.005	-9999	-10000	0	0
POU2F1	0.024	0.031	-9999	-0.59	1	1
T-DHT/AR/DAX-1	-0.049	0.15	-9999	-0.4	43	43
CREBBP	0.014	0	-9999	-10000	0	0
SMARCE1	0.013	0.003	-9999	-10000	0	0

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	-0.008	0.051	-9999	-0.34	12	12
FBXW11	0.014	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.009	0.083	-9999	-0.33	29	29
NF kappa B1 p50/RelA/I kappa B alpha	0.015	0.08	-9999	-0.5	2	2
NFKBIA	-0.01	0.09	-9999	-0.23	59	59
MAPK14	0.014	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.029	0	-9999	-10000	0	0
ARRB2	0.019	0	-9999	-10000	0	0
REL	-0.018	0.13	-9999	-0.56	29	29
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.022	0.046	-9999	-0.28	12	12
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.029	0	-9999	-10000	0	0
PIK3CA	0.013	0.027	-9999	-0.59	1	1
NF kappa B1 p50 dimer	0.022	0	-9999	-10000	0	0
PIK3R1	0.014	0	-9999	-10000	0	0
NFKB1	0.025	0	-9999	-10000	0	0
RELA	0.014	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	-0.002	0.087	-9999	-0.22	43	43
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.019	0.079	-9999	-0.48	2	2
SRC	0.014	0	-9999	-10000	0	0
PI3K	-0.001	0.019	-9999	-0.43	1	1
NF kappa B1 p50/RelA	-0.002	0.087	-9999	-0.22	43	43
IKBKB	0.014	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.014	0	-9999	-10000	0	0
SYK	-0.013	0.12	-9999	-0.57	24	24
I kappa B alpha/PIK3R1	-0.002	0.085	-9999	-0.54	2	2
cell death	0.018	0.076	-9999	-0.46	2	2
NF kappa B1 p105/c-Rel	0.009	0.083	-9999	-0.33	29	29
LCK	-0.081	0.21	-9999	-0.54	89	89
BCL3	0.002	0.076	-9999	-0.49	12	12

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.01	0.04	-10000	0	-0.31	8	8
TRAF2/ASK1	-0.005	0.042	-10000	0	-0.37	7	7
ATM	0.014	0	-10000	0	-10000	0	0
MAP2K3	0.02	0.054	-10000	0	-0.28	5	5
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.019	0.071	-10000	0	-0.41	7	7
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	-0.031	0.15	-10000	0	-0.54	42	42
TXN	0.009	0.01	-10000	0	-0.21	1	1
CALM1	0.012	0.035	-10000	0	-0.54	2	2
GADD45A	-0.018	0.12	-10000	0	-0.49	33	33
GADD45B	-0.026	0.14	-10000	0	-0.52	39	39
MAP3K1	0.007	0.058	-10000	0	-0.49	7	7
MAP3K6	0.007	0.058	-10000	0	-0.49	7	7
MAP3K7	0.014	0	-10000	0	-10000	0	0
MAP3K4	0.014	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	-0.01	0.063	-10000	0	-0.38	14	14
TAK1/TAB family	0.003	0.025	0.18	9	-0.17	1	10
RAC1/OSM/MEKK3	0	0.011	-10000	0	-0.25	1	1
TRAF2	0.014	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.008	0.027	-10000	0	-10000	0	0
TRAF6	0.009	0.016	-10000	0	-0.36	1	1
RAC1	0.014	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.072	0.2	-10000	0	-0.54	80	80
CCM2	0.013	0.022	-10000	0	-0.49	1	1
CaM/Ca2+/CAMKIIB	-0.052	0.12	-10000	0	-0.34	80	80
MAPK11	0.004	0.079	-10000	0	-0.59	9	9
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.05	0.12	-10000	0	-0.31	83	83
OSM/MEKK3	-0.001	0.015	-10000	0	-0.34	1	1
TAOK1	-0.015	0.11	-10000	0	-0.35	47	47
TAOK2	0.019	0	-10000	0	-10000	0	0
TAOK3	0.019	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.014	0	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.006	0.07	-10000	0	-0.59	7	7
MAP3K10	0.005	0.066	-10000	0	-0.49	9	9
MAP3K3	0.014	0	-10000	0	-10000	0	0
TRX/ASK1	0.012	0.047	-10000	0	-0.38	7	7
GADD45/MTK1/MTK1	-0.056	0.13	-10000	0	-0.38	50	50

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.06	0.098	-9999	-0.65	4	4
CRKL	0.035	0.073	-9999	-0.46	4	4
mol:DAG	0.04	0.078	-9999	-0.51	4	4
HRAS	0.057	0.074	-9999	-0.61	2	2
MAPK8	0.014	0.098	-9999	-0.39	19	19
RAP1A	0.035	0.073	-9999	-0.46	4	4
GAB1	0.034	0.079	-9999	-0.53	4	4
MAPK14	0.024	0.073	-9999	-0.37	7	7
EPO	-0.004	0.099	-9999	-0.5	20	20
PLCG1	0.04	0.08	-9999	-0.52	4	4
EPOR/TRPC2/IP3 Receptors	0.015	0.024	-9999	-0.51	1	1
RAPGEF1	0.014	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.062	0.16	-9999	-0.33	136	136
GAB1/SHC/GRB2/SOS1	-0.015	0.062	-9999	-0.51	4	4
EPO/EPOR (dimer)	0.01	0.076	-9999	-0.36	20	20
IRS2	0.034	0.079	-9999	-0.53	4	4
STAT1	0.043	0.097	-9999	-0.5	8	8
STAT5B	0.045	0.083	-9999	-0.56	4	4
cell proliferation	0.022	0.092	-9999	-0.44	9	9
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.016	0.067	-9999	-0.43	8	8
TEC	0.026	0.094	-9999	-0.44	10	10
SOCS3	-0.11	0.23	-9999	-0.52	124	124
STAT1 (dimer)	0.043	0.095	-9999	-0.48	8	8
JAK2	0.015	0.007	-9999	-10000	0	0
PIK3R1	0.014	0	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.042	0.08	-9999	-0.49	4	4
EPO/EPOR	0.01	0.076	-9999	-0.36	20	20
LYN	0.006	0.073	-9999	-0.51	10	10
TEC/VAV2	0.035	0.092	-9999	-0.43	9	9
elevation of cytosolic calcium ion concentration	0.015	0.024	-9999	-0.51	1	1
SHC1	0.009	0.049	-9999	-0.49	5	5
EPO/EPOR (dimer)/LYN	0.022	0.083	-9999	-0.36	14	14
mol:IP3	0.04	0.078	-9999	-0.51	4	4
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.043	0.084	-9999	-0.44	9	9
SH2B3	0.013	0.032	-9999	-0.48	2	2
NFKB1	0.024	0.073	-9999	-0.4	5	5
EPO/EPOR (dimer)/JAK2/SOCS3	-0.039	0.075	-9999	-0.26	14	14
PTPN6	0.028	0.076	-9999	-0.49	4	4
TEC/VAV2/GRB2	0.04	0.09	-9999	-0.41	9	9
EPOR	0.015	0.024	-9999	-0.52	1	1
INPP5D	0.008	0.06	-9999	-0.54	6	6
mol:GDP	-0.015	0.063	-9999	-0.48	5	5
SOS1	0.014	0	-9999	-10000	0	0
PLCG2	0	0.088	-9999	-0.55	13	13
CRKL/CBL/C3G	0.049	0.07	-9999	-0.42	4	4
VAV2	0.035	0.073	-9999	-0.46	4	4
CBL	0.035	0.073	-9999	-0.46	4	4
SHC/Grb2/SOS1	-0.015	0.061	-9999	-0.45	5	5
STAT5A	0.037	0.11	-9999	-0.59	10	10
GRB2	0.013	0.022	-9999	-0.49	1	1
STAT5 (dimer)	0.056	0.12	-9999	-0.57	10	10
LYN/PLCgamma2	0.005	0.093	-9999	-0.47	18	18
PTPN11	0.014	0	-9999	-10000	0	0
BTK	0.023	0.11	-9999	-0.49	15	15
BCL2	0.052	0.15	-9999	-0.92	9	9

×

Nectin adhesion 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.011	0.038	-9999	-0.49	3	3
alphaV beta3 Integrin	-0.046	0.12	-9999	-0.36	66	66
PTK2	-0.03	0.099	-9999	-0.48	19	19
positive regulation of JNK cascade	-0.009	0.045	-9999	-0.31	10	10
CDC42/GDP	0.046	0.073	-9999	-0.41	10	10
Rac1/GDP	0.048	0.073	-9999	-0.41	10	10
RAP1B	0.013	0.022	-9999	-0.49	1	1
RAP1A	0.014	0	-9999	-10000	0	0
CTNNB1	0.014	0	-9999	-10000	0	0
CDC42/GTP	-0.01	0.055	-9999	-0.38	10	10
nectin-3/I-afadin	-0.008	0.059	-9999	-0.43	10	10
RAPGEF1	0.04	0.081	-9999	-0.46	10	10
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.033	0.09	-9999	-0.53	10	10
PDGFB-D/PDGFRB	0.011	0.038	-9999	-0.49	3	3
TLN1	0.032	0.029	-9999	-10000	0	0
Rap1/GTP	-0.009	0.048	-9999	-0.32	10	10
IQGAP1	0.004	0.075	-9999	-0.53	10	10
Rap1/GTP/I-afadin	-0.001	0.018	-9999	-0.33	1	1
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.008	0.059	-9999	-0.43	10	10
PVR	0.014	0	-9999	-10000	0	0
Necl-5(dimer)	0.014	0	-9999	-10000	0	0
mol:GDP	0.044	0.087	-9999	-0.51	10	10
MLLT4	0.013	0.027	-9999	-0.59	1	1
PIK3CA	0.013	0.027	-9999	-0.59	1	1
PI3K	-0.008	0.049	-9999	-0.6	1	1
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.014	0.076	-9999	-0.43	17	17
positive regulation of lamellipodium assembly	-0.009	0.047	-9999	-0.32	10	10
PVRL1	-0.005	0.1	-9999	-0.59	16	16
PVRL3	0.004	0.079	-9999	-0.59	9	9
PVRL2	0.012	0.035	-9999	-0.54	2	2
PIK3R1	0.014	0	-9999	-10000	0	0
CDH1	-0.12	0.24	-9999	-0.54	125	125
CLDN1	-0.019	0.13	-9999	-0.53	31	31
JAM-A/CLDN1	-0.029	0.091	-9999	-0.35	27	27
SRC	-0.019	0.087	-9999	-0.6	10	10
ITGB3	-0.052	0.18	-9999	-0.51	65	65
nectin-1(dimer)/I-afadin/I-afadin	-0.014	0.076	-9999	-0.43	17	17
FARP2	0.037	0.085	-9999	-0.5	10	10
RAC1	0.014	0	-9999	-10000	0	0
CTNNA1	0.014	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.007	0.049	-9999	-0.36	10	10
nectin-1/I-afadin	-0.014	0.076	-9999	-0.43	17	17
nectin-2/I-afadin	-0.002	0.031	-9999	-0.4	3	3
RAC1/GTP/IQGAP1/filamentous actin	-0.006	0.044	-9999	-0.32	10	10
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.018	0.081	-9999	-0.37	25	25
CDC42/GTP/IQGAP1/filamentous actin	-0.006	0.044	-9999	-0.32	10	10
F11R	0.002	0.077	-9999	-0.5	12	12
positive regulation of filopodium formation	-0.009	0.045	-9999	-0.31	10	10
alphaV/beta3 Integrin/Talin	0.013	0.094	-9999	-0.4	4	4
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.002	0.031	-9999	-0.4	3	3
nectin-2(dimer)/I-afadin/I-afadin	-0.002	0.031	-9999	-0.4	3	3
PIP5K1C	0.025	0.031	-9999	-10000	0	0
VAV2	0.037	0.086	-9999	-0.51	10	10
RAP1/GDP	-0.011	0.055	-9999	-0.38	10	10
ITGAV	0.013	0.027	-9999	-0.59	1	1
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.008	0.053	-9999	-0.36	11	11
nectin-3(dimer)/I-afadin/I-afadin	-0.008	0.059	-9999	-0.43	10	10
Rac1/GTP	-0.01	0.057	-9999	-0.39	10	10
PTPRM	0.017	0.034	-9999	-0.22	10	10
E-cadherin/beta catenin/alpha catenin	-0.068	0.12	-9999	-0.59	9	9
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.014	0	-9999	-10000	0	0

×

ceramide signaling pathway

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
MAP4K4	-0.017	0.13	-10000	0	-0.5	17	17
BAG4	-0.001	0.095	-10000	0	-0.59	13	13
BAD	0.008	0.045	-10000	0	-0.19	2	2
NFKBIA	0.014	0	-10000	0	-10000	0	0
BIRC3	-0.033	0.16	-10000	0	-0.55	43	43
BAX	0.008	0.045	-10000	0	-0.19	2	2
EnzymeConsortium:3.1.4.12	-0.003	0.033	-10000	0	-0.1	17	17
IKBKB	-0.007	0.12	-10000	0	-0.46	17	17
MAP2K2	0.018	0.049	-10000	0	-10000	0	0
MAP2K1	0.017	0.052	-10000	0	-0.3	2	2
SMPD1	0.003	0.033	-10000	0	-0.14	2	2
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	-0.01	0.12	-10000	0	-0.47	17	17
MAP2K4	0.011	0.055	-10000	0	-0.28	3	3
protein ubiquitination	-0.006	0.12	-10000	0	-0.46	17	17
EnzymeConsortium:2.7.1.37	0.019	0.057	-10000	0	-0.29	1	1
response to UV	0	0.001	-10000	0	-0.002	3	3
RAF1	0.013	0.049	-10000	0	-10000	0	0
CRADD	0.014	0	-10000	0	-10000	0	0
mol:ceramide	0	0.047	-10000	0	-0.16	12	12
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-10000	0	-10000	0	0
MADD	0.014	0	-10000	0	-10000	0	0
MAP3K1	0.005	0.053	-10000	0	-0.22	9	9
TRADD	0.013	0.027	-10000	0	-0.59	1	1
RELA/p50	0.014	0	-10000	0	-10000	0	0
MAPK3	0.02	0.05	-10000	0	-10000	0	0
MAPK1	0.02	0.05	-10000	0	-10000	0	0
p50/RELA/I-kappa-B-alpha	0	0	-10000	0	-10000	0	0
FADD	-0.016	0.13	-10000	0	-0.5	17	17
KSR1	0.007	0.047	-10000	0	-0.2	2	2
MAPK8	0.01	0.069	-10000	0	-0.26	17	17
TRAF2	0.014	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	-0.007	0.12	-10000	0	-0.51	12	12
TNF R/SODD	-0.018	0.094	-10000	0	-0.44	23	23
TNF	-0.15	0.26	-10000	0	-0.54	156	156
CYCS	0.011	0.044	0.14	4	-0.19	2	6
IKBKG	-0.007	0.12	-10000	0	-0.46	17	17
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.025	0.13	-10000	0	-0.53	17	17
RELA	0.014	0	-10000	0	-10000	0	0
RIPK1	0.014	0	-10000	0	-10000	0	0
AIFM1	0.011	0.044	0.14	4	-0.19	2	6
TNF/TNF R/SODD	-0.11	0.17	-10000	0	-0.39	89	89
TNFRSF1A	0.001	0.085	-10000	0	-0.55	12	12
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.009	0.051	-10000	0	-0.72	1	1
NSMAF	-0.016	0.12	-10000	0	-0.49	17	17
response to hydrogen peroxide	0	0.001	-10000	0	-0.002	3	3
BCL2	0.005	0.075	-10000	0	-0.59	8	8

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.012	0.045	-9999	-10000	0	0
DAPP1	-0.033	0.14	-9999	-0.4	39	39
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.081	0.22	-9999	-0.53	66	66
mol:DAG	-0.024	0.1	-9999	-0.28	29	29
HRAS	0.014	0.003	-9999	-10000	0	0
RAP1A	0.014	0.003	-9999	-10000	0	0
ARF5/GDP	0.03	0.057	-9999	-0.29	6	6
PLCG2	0	0.088	-9999	-0.55	13	13
PLCG1	0.014	0	-9999	-10000	0	0
ARF5	0.014	0	-9999	-10000	0	0
mol:GTP	-0.014	0.051	-9999	-10000	0	0
ARF1/GTP	-0.011	0.042	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
YES1	0.009	0.053	-9999	-0.59	4	4
RAP1A/GTP	-0.014	0.05	-9999	-10000	0	0
ADAP1	-0.028	0.085	-9999	-0.47	8	8
ARAP3	-0.014	0.051	-9999	-10000	0	0
INPPL1	0.014	0	-9999	-10000	0	0
PREX1	0.002	0.084	-9999	-0.59	10	10
ARHGEF6	0.008	0.059	-9999	-0.59	5	5
ARHGEF7	0.014	0	-9999	-10000	0	0
ARF1	0.014	0	-9999	-10000	0	0
NRAS	0.014	0.003	-9999	-10000	0	0
FYN	0.014	0	-9999	-10000	0	0
ARF6	0.014	0	-9999	-10000	0	0
FGR	0.011	0.038	-9999	-0.49	3	3
mol:Ca2+	-0.003	0.057	-9999	-10000	0	0
mol:IP4	0	0	-9999	-10000	0	0
TIAM1	0.013	0.027	-9999	-0.59	1	1
ZAP70	-0.046	0.17	-9999	-0.53	57	57
mol:IP3	-0.008	0.076	-9999	-0.21	11	11
LYN	0.004	0.073	-9999	-0.51	10	10
ARF1/GDP	0.03	0.057	-9999	-0.29	6	6
RhoA/GDP	-0.014	0.043	-9999	-10000	0	0
PDK1/Src/Hsp90	-0.001	0.022	-9999	-0.36	2	2
BLNK	-0.056	0.19	-9999	-0.58	61	61
actin cytoskeleton reorganization	0.044	0.074	-9999	-0.38	5	5
SRC	0.014	0	-9999	-10000	0	0
PLEKHA2	0.028	0.038	-9999	-0.32	6	6
RAC1	0.014	0	-9999	-10000	0	0
PTEN	0.001	0.027	-9999	-0.57	1	1
HSP90AA1	0.014	0	-9999	-10000	0	0
ARF6/GTP	-0.012	0.045	-9999	-10000	0	0
RhoA/GTP	-0.013	0.047	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.075	0.2	-9999	-0.51	58	58
BLK	-0.1	0.22	-9999	-0.52	113	113
PDPK1	0.012	0.038	-9999	-0.59	2	2
CYTH1	-0.013	0.047	-9999	-10000	0	0
HCK	-0.007	0.11	-9999	-0.54	20	20
CYTH3	-0.013	0.047	-9999	-10000	0	0
CYTH2	-0.013	0.047	-9999	-10000	0	0
KRAS	0.013	0.022	-9999	-0.49	1	1
GO:0030676	0	0	-9999	-10000	0	0
FOXO3	0.025	0.087	-9999	-0.45	14	14
SGK1	-0.021	0.083	-9999	-0.49	14	14
INPP5D	0.008	0.06	-9999	-0.54	6	6
mol:GDP	0.023	0.059	-9999	-0.31	6	6
SOS1	0.014	0	-9999	-10000	0	0
SYK	-0.013	0.12	-9999	-0.57	24	24
ARF6/GDP	-0.014	0.043	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.014	0.051	-9999	-10000	0	0
ARAP3/RAP1A/GTP	-0.014	0.051	-9999	-10000	0	0
VAV1	-0.019	0.14	-9999	-0.56	30	30
mol:PI-3-4-P2	0.02	0.044	-9999	-0.38	6	6
RAS family/GTP/PI3K Class I	0.018	0.06	-9999	-10000	0	0
PLEKHA1	0.024	0.05	-9999	-0.3	12	12
Rac1/GDP	0.03	0.057	-9999	-0.29	6	6
LAT	-0.017	0.13	-9999	-0.59	27	27
Rac1/GTP	0.024	0.085	-9999	-0.45	10	10
ITK	-0.063	0.12	-9999	-0.42	20	20
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.04	0.14	-9999	-0.39	35	35
LCK	-0.081	0.21	-9999	-0.54	89	89
BTK	-0.024	0.069	-9999	-0.42	1	1

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.018	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.086	0.03	-9999	-10000	0	0
ERC1	0.013	0.022	-9999	-0.49	1	1
RIP2/NOD2	-0.022	0.088	-9999	-0.37	30	30
NFKBIA	0.05	0	-9999	-10000	0	0
BIRC2	0.014	0	-9999	-10000	0	0
IKBKB	0.014	0	-9999	-10000	0	0
RIPK2	0.014	0	-9999	-10000	0	0
IKBKG	-0.007	0.032	-9999	-10000	0	0
IKK complex/A20	-0.071	0.1	-9999	-0.47	6	6
NEMO/A20/RIP2	0.014	0	-9999	-10000	0	0
XPO1	0.014	0	-9999	-10000	0	0
NEMO/ATM	0.046	0.041	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.014	0	-9999	-10000	0	0
Exportin 1/RanGTP	0	0	-9999	-10000	0	0
IKK complex/ELKS	-0.005	0.024	-9999	-10000	0	0
BCL10/MALT1/TRAF6	-0.001	0.016	-9999	-0.36	1	1
NOD2	-0.017	0.13	-9999	-0.53	30	30
NFKB1	0.018	0	-9999	-10000	0	0
RELA	0.018	0	-9999	-10000	0	0
MALT1	0.014	0	-9999	-10000	0	0
cIAP1/UbcH5C	0	0	-9999	-10000	0	0
ATM	0.014	0	-9999	-10000	0	0
TNF/TNFR1A	-0.12	0.18	-9999	-0.39	165	165
TRAF6	0.013	0.027	-9999	-0.59	1	1
PRKCA	0.013	0.027	-9999	-0.59	1	1
CHUK	0.014	0	-9999	-10000	0	0
UBE2D3	0.014	0	-9999	-10000	0	0
TNF	-0.15	0.26	-9999	-0.54	156	156
NF kappa B1 p50/RelA	0	0	-9999	-10000	0	0
BCL10	0.014	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.05	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.018	0	-9999	-10000	0	0
TNFRSF1A	0.001	0.085	-9999	-0.55	12	12
IKK complex	0.053	0.04	-9999	-10000	0	0
CYLD	0.014	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.006	0.026	-9999	-10000	0	0

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.034	0.029	-9999	-0.29	1	1
positive regulation of NF-kappaB transcription factor activity	0	0.002	-9999	-10000	0	0
CRKL	0.013	0.022	-9999	-0.49	1	1
STAT1 (dimer)/Cbp/p300	0.044	0.095	-9999	-0.43	12	12
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0	0.003	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.055	0.077	-9999	-0.32	21	21
CaM/Ca2+	-0.003	0.025	-9999	-10000	0	0
RAP1A	0.014	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	0.034	0.062	-9999	-0.33	6	6
AKT1	0.052	0.028	-9999	-10000	0	0
MAP2K1	0.046	0.045	-9999	-10000	0	0
MAP3K11	0.041	0.028	-9999	-10000	0	0
IFNGR1	0.016	0.003	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.14	0.19	-9999	-0.46	106	106
Rap1/GTP	-0.002	0.016	-9999	-10000	0	0
CRKL/C3G	-0.001	0.015	-9999	-0.34	1	1
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0	0.024	-9999	-10000	0	0
CEBPB	0.058	0.11	-9999	-0.54	9	9
STAT3	0.014	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.001	0.17	-9999	-1	10	10
STAT1	0.034	0.062	-9999	-0.33	6	6
CALM1	0.012	0.035	-9999	-0.54	2	2
IFN-gamma (dimer)	0.001	0.048	-9999	-0.49	5	5
PIK3CA	0.013	0.027	-9999	-0.59	1	1
STAT1 (dimer)/PIAS1	0.038	0.065	-9999	-0.38	1	1
CEBPB/PTGES2/Cbp/p300	-0.015	0.061	-9999	-0.36	9	9
mol:Ca2+	0.022	0.03	-9999	-0.29	1	1
MAPK3	0.053	0.051	-9999	-10000	0	0
STAT1 (dimer)	-0.072	0.11	-9999	-0.46	21	21
MAPK1	0.053	0.051	-9999	-10000	0	0
JAK2	0.016	0.003	-9999	-10000	0	0
PIK3R1	0.014	0	-9999	-10000	0	0
JAK1	0.016	0.003	-9999	-10000	0	0
CAMK2D	0.013	0.027	-9999	-0.59	1	1
DAPK1	0.049	0.13	-9999	-0.63	18	18
SMAD7	0.005	0.065	-9999	-0.19	3	3
CBL/CRKL/C3G	0.037	0.033	-9999	-10000	0	0
PI3K	-0.002	0.021	-9999	-10000	0	0
IFNG	0.001	0.049	-9999	-0.49	5	5
apoptosis	0.03	0.097	-9999	-0.45	18	18
CAMK2G	0.013	0.027	-9999	-0.59	1	1
STAT3 (dimer)	0.014	0	-9999	-10000	0	0
CAMK2A	-0.23	0.28	-9999	-0.54	230	230
CAMK2B	-0.072	0.2	-9999	-0.54	80	80
FRAP1	0.05	0.027	-9999	-10000	0	0
PRKCD	0.038	0.073	-9999	-10000	0	0
RAP1B	0.013	0.022	-9999	-0.49	1	1
negative regulation of cell growth	-0.055	0.077	-9999	-0.32	21	21
PTPN2	0.014	0	-9999	-10000	0	0
EP300	0.01	0.053	-9999	-0.59	4	4
IRF1	0.032	0.14	-9999	-0.58	18	18
STAT1 (dimer)/PIASy	0.04	0.062	-9999	-0.39	1	1
SOCS1	-0.047	0.2	-9999	-1.4	8	8
mol:GDP	-0.001	0.019	-9999	-10000	0	0
CASP1	-0.004	0.089	-9999	-0.28	28	28
PTGES2	0.014	0	-9999	-10000	0	0
IRF9	0.05	0.047	-9999	-0.24	4	4
mol:PI-3-4-5-P3	-0.002	0.021	-9999	-10000	0	0
RAP1/GDP	-0.002	0.017	-9999	-10000	0	0
CBL	0.041	0.027	-9999	-10000	0	0
MAP3K1	0.038	0.042	-9999	-10000	0	0
PIAS1	0.009	0.053	-9999	-0.59	4	4
PIAS4	0.014	0.002	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.055	0.077	-9999	-0.32	21	21
PTPN11	0.034	0.028	-9999	-0.29	1	1
CREBBP	0.014	0.001	-9999	-10000	0	0
RAPGEF1	0.014	0	-9999	-10000	0	0

×

Signaling events mediated by PRL

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
CCNE1	0.011	0.038	-10000	0	-0.49	3	3
mol:Halofuginone	0.005	0.01	-10000	0	-0.23	1	1
ITGA1	-0.012	0.12	-10000	0	-0.52	25	25
CDKN1A	-0.023	0.11	-10000	0	-0.45	20	20
PRL-3/alpha Tubulin	-0.003	0.033	-10000	0	-0.34	5	5
mol:Ca2+	-0.02	0.095	0.23	3	-0.43	25	28
AGT	-0.015	0.13	-10000	0	-0.58	25	25
CCNA2	-0.056	0.16	-10000	0	-0.52	15	15
TUBA1B	0.014	0	-10000	0	-10000	0	0
EGR1	-0.063	0.17	-10000	0	-0.38	115	115
CDK2/Cyclin E1	-0.013	0.12	-10000	0	-0.43	21	21
MAPK3	0.021	0.036	-10000	0	-0.34	5	5
PRL-2 /Rab GGTase beta	0	0	-10000	0	-10000	0	0
MAPK1	0.021	0.036	-10000	0	-0.34	5	5
PTP4A1	-0.03	0.14	-10000	0	-0.95	1	1
PTP4A3	0.009	0.049	-10000	0	-0.49	5	5
PTP4A2	0.014	0	-10000	0	-10000	0	0
ITGB1	0.02	0.042	-10000	0	-0.34	7	7
SRC	0.014	0	-10000	0	-10000	0	0
RAC1	0.004	0.061	-10000	0	-0.27	1	1
Rab GGTase beta/Rab GGTase alpha	0	0	-10000	0	-10000	0	0
PRL-1/ATF-5	-0.024	0.13	-10000	0	-0.9	1	1
RABGGTA	0.014	0	-10000	0	-10000	0	0
BCAR1	0.001	0.03	0.23	5	-0.44	1	6
RHOC	0.003	0.064	-10000	0	-0.33	2	2
RHOA	0.004	0.061	-10000	0	-0.27	1	1
cell motility	0.006	0.066	-10000	0	-0.3	1	1
PRL-1/alpha Tubulin	-0.021	0.13	-10000	0	-0.9	1	1
PRL-3/alpha1 Integrin	-0.021	0.088	-10000	0	-0.38	29	29
ROCK1	0.006	0.066	-10000	0	-0.3	1	1
RABGGTB	0.014	0	-10000	0	-10000	0	0
CDK2	0	0.086	-10000	0	-0.53	13	13
mitosis	-0.03	0.14	-10000	0	-0.94	1	1
ATF5	0.007	0.058	-10000	0	-0.49	7	7

×

Circadian rhythm 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
chromatin modification	0.032	0.085	-10000	0	-0.54	6	6
CLOCK	-0.018	0.14	-10000	0	-0.59	30	30
TIMELESS/CRY2	0.025	0.082	-10000	0	-0.64	1	1
DEC1/BMAL1	0.008	0.059	-10000	0	-0.34	14	14
ATR	0.014	0	-10000	0	-10000	0	0
NR1D1	0.025	0.12	-10000	0	-1.4	3	3
ARNTL	0.014	0.039	-10000	0	-0.5	3	3
TIMELESS	0.025	0.08	-10000	0	-10000	0	0
NPAS2	0.006	0.079	-10000	0	-0.55	10	10
CRY2	0.008	0.059	-10000	0	-0.59	5	5
mol:CO	-0.012	0.019	0.084	16	-10000	0	16
CHEK1	0.008	0.054	-10000	0	-0.49	6	6
mol:HEME	0.012	0.019	-10000	0	-0.084	16	16
PER1	0.004	0.079	-10000	0	-0.59	9	9
BMAL/CLOCK/NPAS2	0.013	0.11	-10000	0	-0.36	37	37
BMAL1/CLOCK	0.016	0.13	-10000	0	-0.78	5	5
S phase of mitotic cell cycle	0.032	0.085	-10000	0	-0.54	6	6
TIMELESS/CHEK1/ATR	0.033	0.086	-10000	0	-0.55	6	6
mol:NADPH	0.012	0.019	-10000	0	-0.084	16	16
PER1/TIMELESS	0.022	0.084	-10000	0	-10000	0	0
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	-0.002	0.072	-10000	0	-0.49	11	11

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.011	0.038	-9999	-0.49	3	3
mol:S1P	0.001	0.003	-9999	-10000	0	0
S1P1/S1P/Gi	0.026	0.06	-9999	-0.27	17	17
GNAO1	0.01	0.06	-9999	-0.6	5	5
S1P/S1P3/G12/G13	0.003	0.09	-9999	-0.28	47	47
AKT1	0.027	0.04	-9999	-0.3	2	2
AKT3	0.027	0.14	-9999	-1.3	5	5
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.011	0.038	-9999	-0.49	3	3
GNAI2	0.016	0.002	-9999	-10000	0	0
GNAI3	0.016	0.002	-9999	-10000	0	0
GNAI1	-0.003	0.11	-9999	-0.59	16	16
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	-0.032	0.15	-9999	-0.51	47	47
S1PR2	0.008	0.062	-9999	-0.56	6	6
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.019	0.092	-9999	-0.49	7	7
MAPK3	0.027	0.088	-9999	-0.46	7	7
MAPK1	0.027	0.088	-9999	-0.46	7	7
JAK2	0.024	0.096	-9999	-0.42	11	11
CXCR4	0.013	0.11	-9999	-0.44	14	14
FLT1	0.016	0.028	-9999	-0.62	1	1
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.027	0.088	-9999	-0.46	7	7
S1P/S1P3/Gi	0.019	0.093	-9999	-0.49	7	7
RAC1	0.014	0	-9999	-10000	0	0
RhoA/GTP	-0.02	0.07	-9999	-0.44	7	7
VEGFA	-0.004	0.1	-9999	-0.49	22	22
S1P/S1P2/Gi	0.031	0.069	-9999	-0.34	10	10
VEGFR1 homodimer/VEGFA homodimer	0.013	0.077	-9999	-0.34	23	23
RHOA	0.014	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.009	0.11	-9999	-0.3	49	49
GNAQ	0.014	0	-9999	-10000	0	0
GNAZ	0.016	0.002	-9999	-10000	0	0
G12/G13	-0.001	0.019	-9999	-0.43	1	1
GNA14	-0.014	0.12	-9999	-0.56	25	25
GNA15	-0.007	0.11	-9999	-0.57	19	19
GNA12	0.013	0.027	-9999	-0.59	1	1
GNA13	0.014	0	-9999	-10000	0	0
GNA11	0.004	0.079	-9999	-0.59	9	9
Rac1/GTP	-0.02	0.07	-9999	-0.44	7	7

×

Class IB PI3K non-lipid kinase events

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
cAMP biosynthetic process	-0.004	0.076	0.57	9	-10000	0	9
PI3K Class IB/PDE3B	0.004	0.077	-10000	0	-0.57	9	9
PDE3B	0.004	0.077	-10000	0	-0.57	9	9

×

HIF-2-alpha transcription factor network

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
MMP14	-0.05	0.21	-10000	0	-1.1	17	17
oxygen homeostasis	0.007	0.017	-10000	0	-10000	0	0
TCEB2	0.014	0	-10000	0	-10000	0	0
TCEB1	0.014	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.005	0.048	-10000	0	-0.31	4	4
EPO	0.092	0.23	-10000	0	-0.72	14	14
FIH (dimer)	0.021	0.017	-10000	0	-10000	0	0
APEX1	0.02	0.017	-10000	0	-10000	0	0
SERPINE1	0.01	0.33	-10000	0	-0.7	35	35
FLT1	-0.004	0.1	-10000	0	-0.84	6	6
ADORA2A	0.091	0.23	-10000	0	-0.72	13	13
germ cell development	0.075	0.25	-10000	0	-0.7	19	19
SLC11A2	0.093	0.23	-10000	0	-0.73	13	13
BHLHE40	0.084	0.25	-10000	0	-0.78	18	18
HIF1AN	0.021	0.017	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.024	0.085	-10000	0	-0.44	8	8
ETS1	0.018	0.084	-10000	0	-0.55	11	11
CITED2	0.003	0.037	-10000	0	-10000	0	0
KDR	-0.012	0.13	-10000	0	-0.83	10	10
PGK1	0.093	0.23	-10000	0	-0.73	13	13
SIRT1	0.015	0.001	-10000	0	-10000	0	0
response to hypoxia	0	0.002	-10000	0	-10000	0	0
HIF2A/ARNT	0.099	0.27	-10000	0	-0.91	13	13
EPAS1	0.066	0.11	-10000	0	-0.35	7	7
SP1	0.019	0.017	-10000	0	-10000	0	0
ABCG2	0.092	0.24	-10000	0	-0.78	13	13
EFNA1	0.092	0.24	-10000	0	-0.75	14	14
FXN	0.092	0.23	-10000	0	-0.72	13	13
POU5F1	0.074	0.26	-10000	0	-0.74	19	19
neuron apoptosis	-0.098	0.26	0.86	13	-10000	0	13
EP300	0.009	0.053	-10000	0	-0.59	4	4
EGLN3	0.006	0.098	-10000	0	-0.59	13	13
EGLN2	0.021	0.017	-10000	0	-10000	0	0
EGLN1	0.021	0.017	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0	0	-10000	0	-10000	0	0
VHL	0.014	0	-10000	0	-10000	0	0
ARNT	0.019	0.029	-10000	0	-0.52	1	1
SLC2A1	0.091	0.23	-10000	0	-0.73	13	13
TWIST1	0.065	0.28	-10000	0	-0.75	25	25
ELK1	0.023	0.002	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.023	0.085	-10000	0	-0.44	8	8
VEGFA	0.085	0.25	-10000	0	-0.76	18	18
CREBBP	0.014	0	-10000	0	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.046	0.12	-9999	-0.36	66	66
AKT1	0.074	0.085	-9999	-0.64	3	3
PTK2B	-0.001	0.14	-9999	-0.48	23	23
VEGFR2 homodimer/Frs2	0.029	0.073	-9999	-0.72	3	3
CAV1	-0.05	0.17	-9999	-0.49	65	65
CALM1	0.012	0.035	-9999	-0.54	2	2
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.018	0.08	-9999	-0.61	5	5
endothelial cell proliferation	0.061	0.1	-9999	-0.49	4	4
mol:Ca2+	0.036	0.092	-9999	-0.55	5	5
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.021	0.083	-9999	-0.6	6	6
RP11-342D11.1	0.027	0.092	-9999	-0.56	5	5
CDH5	0.011	0.038	-9999	-0.49	3	3
VEGFA homodimer	-0.012	0.052	-9999	-0.32	1	1
SHC1	0.009	0.049	-9999	-0.49	5	5
SHC2	0.013	0.027	-9999	-0.59	1	1
HRAS/GDP	-0.019	0.072	-9999	-0.49	6	6
SH2D2A	-0.073	0.2	-9999	-0.54	81	81
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.022	0.07	-9999	-0.49	5	5
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.059	0.14	-9999	-0.59	15	15
VEGFR1 homodimer	0.013	0.027	-9999	-0.59	1	1
SHC/GRB2/SOS1	-0.021	0.08	-9999	-0.55	6	6
GRB10	0.035	0.1	-9999	-0.57	7	7
PTPN11	0.014	0	-9999	-10000	0	0
GRB2	0.013	0.022	-9999	-0.49	1	1
PAK1	-0.035	0.15	-9999	-0.5	49	49
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.021	0.088	-9999	-0.62	7	7
HRAS	0.014	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	0.027	0.078	-9999	-0.37	5	5
HIF1A	0.012	0.035	-9999	-0.54	2	2
FRS2	0.012	0.035	-9999	-0.54	2	2
oxygen and reactive oxygen species metabolic process	-0.021	0.082	-9999	-0.59	6	6
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.005	0.071	-9999	-0.52	9	9
Nck/Pak	-0.034	0.1	-9999	-0.35	50	50
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.017	0.079	-9999	-0.61	5	5
mol:GDP	-0.021	0.078	-9999	-0.5	8	8
mol:NADP	0.061	0.081	-9999	-0.44	5	5
eNOS/Hsp90	0.065	0.077	-9999	-0.4	5	5
PIK3R1	0.014	0	-9999	-10000	0	0
mol:IP3	0.036	0.093	-9999	-0.56	5	5
HIF1A/ARNT	-0.002	0.028	-9999	-0.37	3	3
SHB	0.014	0	-9999	-10000	0	0
VEGFA	-0.005	0.1	-9999	-0.48	22	22
VEGFC	-0.004	0.098	-9999	-0.52	18	18
FAK1/Vinculin	0.035	0.11	-9999	-0.62	6	6
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.046	0.12	-9999	-0.5	22	22
PTPN6	-0.003	0.099	-9999	-0.55	16	16
EPAS1	0.02	0.038	-9999	-0.34	3	3
mol:L-citrulline	0.061	0.081	-9999	-0.44	5	5
ITGAV	0.013	0.027	-9999	-0.59	1	1
PIK3CA	0.013	0.027	-9999	-0.59	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.018	0.075	-9999	-0.58	5	5
VEGFR2 homodimer/VEGFA homodimer	-0.023	0.086	-9999	-0.61	5	5
VEGFR2/3 heterodimer	0.025	0.091	-9999	-0.74	5	5
VEGFB	0.013	0.022	-9999	-0.49	1	1
MAPK11	0.035	0.099	-9999	-0.54	7	7
VEGFR2 homodimer	0.029	0.08	-9999	-0.54	9	9
FLT1	0.013	0.027	-9999	-0.59	1	1
NEDD4	0.005	0.078	-9999	-0.52	11	11
MAPK3	0.029	0.098	-9999	-0.5	5	5
MAPK1	0.029	0.098	-9999	-0.5	5	5
VEGFA145/NRP2	-0.022	0.089	-9999	-0.37	31	31
VEGFR1/2 heterodimer	0.03	0.072	-9999	-0.72	3	3
KDR	0.029	0.081	-9999	-0.54	9	9
VEGFA165/NRP1/VEGFR2 homodimer	0.029	0.1	-9999	-0.53	6	6
SRC	0.014	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.031	0.099	-9999	-0.49	6	6
PI3K	0.061	0.092	-9999	-0.67	3	3
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.018	0.08	-9999	-0.61	5	5
FES	0.034	0.098	-9999	-0.55	6	6
GAB1	-0.017	0.074	-9999	-0.63	5	5
VEGFR2 homodimer/VEGFA homodimer/Src	-0.017	0.079	-9999	-0.61	5	5
CTNNB1	0.014	0	-9999	-10000	0	0
SOS1	0.014	0	-9999	-10000	0	0
ARNT	0.013	0.022	-9999	-0.49	1	1
eNOS/Caveolin-1	0.038	0.11	-9999	-0.48	6	6
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.019	0.084	-9999	-0.6	6	6
PI3K/GAB1	0.075	0.085	-9999	-0.55	4	4
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.035	0.09	-9999	-0.55	6	6
PRKACA	0.014	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.019	0.094	-9999	-0.64	7	7
HSP90AA1	0.014	0	-9999	-10000	0	0
CDC42	0.036	0.094	-9999	-0.57	5	5
actin cytoskeleton reorganization	-0.059	0.13	-9999	-0.58	15	15
PTK2	0.031	0.11	-9999	-0.62	5	5
EDG1	0.027	0.092	-9999	-0.56	5	5
mol:DAG	0.036	0.093	-9999	-0.56	5	5
CaM/Ca2+	-0.02	0.071	-9999	-0.51	5	5
MAP2K3	0.034	0.11	-9999	-0.55	7	7
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.035	0.1	-9999	-0.59	7	7
PLCG1	0.036	0.094	-9999	-0.57	5	5
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.016	0.072	-9999	-0.58	5	5
IQGAP1	0.004	0.075	-9999	-0.53	10	10
YES1	0.009	0.053	-9999	-0.59	4	4
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.017	0.079	-9999	-0.61	5	5
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.026	0.094	-9999	-0.59	7	7
cell migration	0.058	0.11	-9999	-0.56	7	7
mol:PI-3-4-5-P3	0.06	0.087	-9999	-0.61	3	3
FYN	0.014	0	-9999	-10000	0	0
VEGFB/NRP1	0.033	0.088	-9999	-0.52	5	5
mol:NO	0.061	0.081	-9999	-0.44	5	5
PXN	0.014	0	-9999	-10000	0	0
HRAS/GTP	-0.019	0.072	-9999	-0.49	6	6
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.035	0.1	-9999	-0.58	7	7
VHL	0.014	0	-9999	-10000	0	0
ITGB3	-0.052	0.18	-9999	-0.51	65	65
NOS3	0.062	0.088	-9999	-0.49	5	5
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.018	0.082	-9999	-0.61	6	6
RAC1	0.014	0	-9999	-10000	0	0
PRKCA	0.043	0.089	-9999	-0.52	5	5
PRKCB	0.005	0.14	-9999	-0.5	18	18
VCL	0.008	0.058	-9999	-0.52	6	6
VEGFA165/NRP1	0.027	0.093	-9999	-0.56	5	5
VEGFR1/2 heterodimer/VEGFA homodimer	-0.018	0.08	-9999	-0.61	5	5
VEGFA165/NRP2	-0.022	0.089	-9999	-0.37	31	31
MAPKKK cascade	0.057	0.098	-9999	-0.52	7	7
NRP2	0.003	0.08	-9999	-0.56	10	10
VEGFC homodimer	-0.004	0.098	-9999	-0.52	18	18
NCK1	0.013	0.027	-9999	-0.59	1	1
ROCK1	0.014	0	-9999	-10000	0	0
FAK1/Paxillin	0.038	0.1	-9999	-0.57	5	5
MAP3K13	0.028	0.11	-9999	-0.56	6	6
PDPK1	0.065	0.085	-9999	-0.61	3	3

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.032	0.042	-9999	-0.53	2	2
VEGFR1 homodimer/NRP1	0.022	0.039	-9999	-0.54	2	2
mol:DAG	-0.019	0.13	-9999	-0.66	1	1
VEGFR1 homodimer/NRP1/VEGFR 121	-0.013	0.06	-9999	-0.49	2	2
CaM/Ca2+	-0.012	0.12	-9999	-0.57	2	2
HIF1A	0.02	0.038	-9999	-0.46	3	3
GAB1	0.012	0.035	-9999	-0.54	2	2
AKT1	0.005	0.13	-9999	-0.71	2	2
PLCG1	-0.02	0.13	-9999	-0.66	1	1
NOS3	0.007	0.13	-9999	-0.47	4	4
CBL	0.014	0	-9999	-10000	0	0
mol:NO	0.008	0.12	-9999	-0.45	4	4
FLT1	0.03	0.045	-9999	-0.62	2	2
PGF	-0.092	0.22	-9999	-0.55	96	96
VEGFR1 homodimer/NRP2/VEGFR121	0.021	0.082	-9999	-0.58	2	2
CALM1	0.012	0.035	-9999	-0.54	2	2
PIK3CA	0.013	0.027	-9999	-0.59	1	1
eNOS/Hsp90	0.015	0.12	-9999	-0.43	4	4
endothelial cell proliferation	-0.033	0.16	-9999	-0.52	16	16
mol:Ca2+	-0.019	0.13	-9999	-0.65	1	1
MAPK3	-0.001	0.12	-9999	-0.57	1	1
MAPK1	-0.001	0.12	-9999	-0.57	1	1
PIK3R1	0.014	0	-9999	-10000	0	0
PLGF homodimer	-0.091	0.22	-9999	-0.55	96	96
PRKACA	0.014	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.05	0.17	-9999	-0.49	65	65
VEGFA homodimer	-0.007	0.1	-9999	-0.49	22	22
VEGFR1 homodimer/VEGFA homodimer	0.02	0.073	-9999	-0.53	2	2
platelet activating factor biosynthetic process	0.007	0.11	-9999	-0.55	1	1
PI3K	-0.011	0.13	-9999	-0.61	2	2
PRKCA	-0.01	0.12	-9999	-0.61	1	1
PRKCB	-0.049	0.16	-9999	-0.55	16	16
VEGFR1 homodimer/PLGF homodimer	-0.034	0.14	-9999	-0.36	62	62
VEGFA	-0.007	0.1	-9999	-0.49	22	22
VEGFB	0.013	0.022	-9999	-0.49	1	1
mol:IP3	-0.019	0.13	-9999	-0.66	1	1
RASA1	0.04	0.039	-9999	-0.66	1	1
NRP2	0.003	0.08	-9999	-0.56	10	10
VEGFR1 homodimer	0.03	0.045	-9999	-0.62	2	2
VEGFB homodimer	0.013	0.022	-9999	-0.49	1	1
NCK1	0.013	0.027	-9999	-0.59	1	1
eNOS/Caveolin-1	-0.014	0.14	-9999	-0.44	17	17
PTPN11	0.014	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.05	0.11	-9999	-0.6	2	2
mol:L-citrulline	0.008	0.12	-9999	-0.45	4	4
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.035	0.063	-9999	-0.63	1	1
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.027	0.069	-9999	-0.67	1	1
CD2AP	0.014	0	-9999	-10000	0	0
PI3K/GAB1	-0.048	0.1	-9999	-0.57	2	2
PDPK1	-0.003	0.12	-9999	-0.71	2	2
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.028	0.067	-9999	-0.67	1	1
mol:NADP	0.008	0.12	-9999	-0.45	4	4
HSP90AA1	0.014	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.011	0.053	-9999	-0.62	1	1
VEGFR1 homodimer/NRP2	0.026	0.064	-9999	-0.39	9	9

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.009	0.053	-9999	-0.59	4	4
HDAC2	0.014	0.001	-9999	-10000	0	0
GNB1/GNG2	-0.008	0.052	-9999	-0.36	11	11
forebrain development	-0.005	0.15	-9999	-0.43	43	43
GNAO1	0.008	0.06	-9999	-0.6	5	5
SMO/beta Arrestin2	0.016	0.053	-9999	-0.43	7	7
SMO	0.006	0.07	-9999	-0.59	7	7
ARRB2	0.014	0.004	-9999	-10000	0	0
GLI3/SPOP	0.04	0.067	-9999	-0.6	1	1
mol:GTP	0	0.002	-9999	-10000	0	0
GSK3B	0.013	0.027	-9999	-0.59	1	1
GNAI2	0.014	0.003	-9999	-10000	0	0
SIN3/HDAC complex	0.004	0.019	-9999	-0.32	1	1
GNAI1	-0.005	0.1	-9999	-0.59	16	16
XPO1	0.015	0.005	-9999	-10000	0	0
GLI1/Su(fu)	-0.042	0.11	-9999	-0.51	14	14
SAP30	0.013	0.027	-9999	-0.59	1	1
mol:GDP	0.006	0.07	-9999	-0.59	7	7
MIM/GLI2A	0.01	0.059	-9999	-0.58	5	5
IFT88	0.014	0	-9999	-10000	0	0
GNAI3	0.014	0.003	-9999	-10000	0	0
GLI2	0.043	0.036	-9999	-10000	0	0
GLI3	0.034	0.07	-9999	-0.48	2	2
CSNK1D	0.014	0	-9999	-10000	0	0
CSNK1E	0.014	0	-9999	-10000	0	0
SAP18	0.014	0.001	-9999	-10000	0	0
embryonic digit morphogenesis	0.014	0	-9999	-10000	0	0
GNG2	0.009	0.053	-9999	-0.59	4	4
Gi family/GTP	0.025	0.067	-9999	-0.28	16	16
SIN3B	0.014	0.001	-9999	-10000	0	0
SIN3A	0.014	0.001	-9999	-10000	0	0
GLI3/Su(fu)	0.052	0.058	-9999	-0.46	2	2
GLI2/Su(fu)	0.053	0.057	-9999	-0.77	1	1
FOXA2	-0.039	0.13	-9999	-0.99	4	4
neural tube patterning	-0.005	0.15	-9999	-0.43	43	43
SPOP	0.014	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.027	0.051	-9999	-0.39	5	5
GNB1	0.014	0	-9999	-10000	0	0
CSNK1G2	0.014	0	-9999	-10000	0	0
CSNK1G3	0.014	0	-9999	-10000	0	0
MTSS1	0.01	0.059	-9999	-0.58	5	5
embryonic limb morphogenesis	-0.005	0.15	-9999	-0.43	43	43
SUFU	0.026	0.045	-9999	-0.78	1	1
LGALS3	-0.026	0.14	-9999	-0.5	41	41
catabolic process	0.064	0.064	-9999	-0.49	1	1
GLI3A/CBP	-0.017	0.1	-9999	-0.34	32	32
KIF3A	0.013	0.027	-9999	-0.59	1	1
GLI1	-0.006	0.16	-9999	-0.44	43	43
RAB23	0.013	0.027	-9999	-0.59	1	1
CSNK1A1	0.014	0	-9999	-10000	0	0
IFT172	0.011	0.046	-9999	-0.59	3	3
RBBP7	0.014	0.001	-9999	-10000	0	0
Su(fu)/Galectin3	0.008	0.089	-9999	-0.36	10	10
GNAZ	0.014	0.003	-9999	-10000	0	0
RBBP4	0.013	0.027	-9999	-0.59	1	1
CSNK1G1	0.013	0.022	-9999	-0.49	1	1
PIAS1	0.009	0.053	-9999	-0.59	4	4
PRKACA	0.014	0	-9999	-10000	0	0
GLI2/SPOP	0.047	0.034	-9999	-10000	0	0
STK36	0.014	0.027	-9999	-0.59	1	1
Gi family/GNB1/GNG2/GDP	0.031	0.069	-9999	-0.36	6	6
PTCH1	-0.006	0.19	-9999	-0.83	15	15
MIM/GLI1	-0.007	0.17	-9999	-0.52	26	26
CREBBP	-0.017	0.1	-9999	-0.34	32	32
Su(fu)/SIN3/HDAC complex	0.051	0.03	-9999	-0.28	1	1

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	-0.085	0.13	-10000	0	-0.35	80	80
Ran/GTP/Exportin 1/HDAC1	-0.002	0.023	-10000	0	-0.26	4	4
NF kappa B1 p50/RelA/I kappa B alpha	-0.034	0.14	-10000	0	-0.51	3	3
SUMO1	0.014	0	-10000	0	-10000	0	0
ZFPM1	0.013	0.027	-10000	0	-0.59	1	1
NPC/RanGAP1/SUMO1/Ubc9	0.024	0	-10000	0	-10000	0	0
FKBP3	0.014	0	-10000	0	-10000	0	0
Histones	-0.005	0.087	-10000	0	-0.44	4	4
YY1/LSF	0.031	0.029	-10000	0	-0.34	1	1
SMG5	0.013	0.022	-10000	0	-0.49	1	1
RAN	0.014	0	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	-0.041	0.12	-10000	0	-0.44	3	3
I kappa B alpha/HDAC1	-0.024	0.094	-10000	0	-0.39	7	7
SAP18	0.014	0	-10000	0	-10000	0	0
RELA	-0.031	0.11	-10000	0	-0.38	6	6
HDAC1/Smad7	-0.003	0.031	-10000	0	-0.36	4	4
RANGAP1	0.014	0	-10000	0	-10000	0	0
HDAC3/TR2	-0.021	0.086	-10000	0	-0.29	3	3
NuRD/MBD3 Complex	0.05	0.023	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.022	0.1	-10000	0	-0.35	6	6
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	-0.004	0.1	-10000	0	-0.56	16	16
GATA1	0.004	0.058	-10000	0	-0.49	7	7
Mad/Max	0	0	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.058	0.029	-10000	0	-10000	0	0
RBBP7	0.014	0	-10000	0	-10000	0	0
NPC	0	0	-10000	0	-10000	0	0
RBBP4	0.013	0.027	-10000	0	-0.59	1	1
MAX	0.014	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.014	0	-10000	0	-10000	0	0
NFKBIA	-0.033	0.097	-10000	0	-0.33	3	3
KAT2B	0.013	0.022	-10000	0	-0.49	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.045	0.026	-10000	0	-10000	0	0
SIN3 complex	-0.001	0.014	-10000	0	-0.32	1	1
SMURF1	0.014	0	-10000	0	-10000	0	0
CHD3	0.013	0.027	-10000	0	-0.59	1	1
SAP30	0.013	0.027	-10000	0	-0.59	1	1
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.012	0.038	-10000	0	-0.59	2	2
YY1/HDAC3	-0.007	0.084	-10000	0	-0.3	4	4
YY1/HDAC2	0.032	0.025	-10000	0	-10000	0	0
YY1/HDAC1	0.029	0.041	-10000	0	-0.34	4	4
NuRD/MBD2 Complex (MeCP1)	0.05	0.023	-10000	0	-10000	0	0
PPARG	-0.091	0.14	-10000	0	-0.35	94	94
HDAC8/hEST1B	-0.001	0.02	-10000	0	-0.32	2	2
UBE2I	0.014	0	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.014	0	-10000	0	-10000	0	0
TNFRSF1A	0.001	0.085	-10000	0	-0.55	12	12
HDAC3/SMRT (N-CoR2)	-0.021	0.086	-10000	0	-0.29	3	3
MBD3L2	0	0.001	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.003	0.031	-10000	0	-0.36	4	4
CREBBP	0.014	0	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.053	0.024	-10000	0	-10000	0	0
HDAC1	0.009	0.053	-10000	0	-0.59	4	4
HDAC3	-0.033	0.097	-10000	0	-0.33	3	3
HDAC2	0.014	0	-10000	0	-10000	0	0
YY1	0.03	0.029	-10000	0	-0.28	4	4
HDAC8	0.013	0.027	-10000	0	-0.59	1	1
SMAD7	0.014	0	-10000	0	-10000	0	0
NCOR2	0.014	0	-10000	0	-10000	0	0
MXD1	0.014	0	-10000	0	-10000	0	0
STAT3	0.025	0.033	-10000	0	-0.34	4	4
NFKB1	0.014	0	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.014	0	-10000	0	-10000	0	0
YY1/LSF/HDAC1	0.035	0.04	-10000	0	-0.31	5	5
YY1/SAP30/HDAC1	0.035	0.04	-10000	0	-0.31	5	5
EP300	0.009	0.053	-10000	0	-0.59	4	4
STAT3 (dimer non-phopshorylated)	0.025	0.032	-10000	0	-0.34	4	4
proteasomal ubiquitin-dependent protein catabolic process	-0.032	0.096	-10000	0	-0.33	3	3
histone deacetylation	0.05	0.023	-10000	0	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	-0.01	0.085	-10000	0	-0.36	3	3
nuclear export	0.001	0.02	0.32	2	-10000	0	2
PRKACA	0.014	0	-10000	0	-10000	0	0
GATAD2B	0.014	0	-10000	0	-10000	0	0
GATAD2A	0.014	0	-10000	0	-10000	0	0
GATA2/HDAC3	-0.031	0.1	-10000	0	-0.36	14	14
GATA1/HDAC1	-0.008	0.054	-10000	0	-0.37	11	11
GATA1/HDAC3	-0.032	0.089	-10000	0	-0.34	5	5
CHD4	0.014	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A	-0.12	0.18	-10000	0	-0.39	165	165
SIN3/HDAC complex/Mad/Max	0.05	0.023	-10000	0	-10000	0	0
NuRD Complex	0.058	0.024	-10000	0	-10000	0	0
positive regulation of chromatin silencing	-0.038	0.066	-10000	0	-0.43	4	4
SIN3B	0.014	0	-10000	0	-10000	0	0
MTA2	0.014	0	-10000	0	-10000	0	0
SIN3A	0.014	0	-10000	0	-10000	0	0
XPO1	0.014	0	-10000	0	-10000	0	0
SUMO1/HDAC1	0.031	0.028	-10000	0	-0.29	4	4
HDAC complex	-0.003	0.031	-10000	0	-0.32	5	5
GATA1/Fog1	-0.005	0.044	-10000	0	-0.35	8	8
FKBP25/HDAC1/HDAC2	-0.003	0.031	-10000	0	-0.36	4	4
TNF	-0.15	0.26	-10000	0	-0.54	156	156
negative regulation of cell growth	0.05	0.023	-10000	0	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.05	0.023	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0	0	-10000	0	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.044	0.14	-10000	0	-0.33	80	80
SIN3/HDAC complex/NCoR1	0.047	0.03	-10000	0	-0.39	1	1
TFCP2	0.013	0.027	-10000	0	-0.59	1	1
NR2C1	0.014	0	-10000	0	-10000	0	0
MBD3	0.014	0	-10000	0	-10000	0	0
MBD2	0.014	0	-10000	0	-10000	0	0

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.011	0.054	-9999	-0.57	1	1
TC10/GTP	-0.008	0.048	-9999	-0.55	1	1
Insulin Receptor/Insulin/IRS1/Shp2	-0.003	0.027	-9999	-0.29	4	4
HRAS	0.014	0	-9999	-10000	0	0
APS homodimer	-0.001	0.094	-9999	-0.56	14	14
GRB14	-0.18	0.26	-9999	-0.53	186	186
FOXO3	-0.027	0.096	-9999	-0.59	14	14
AKT1	-0.04	0.13	-9999	-0.45	4	4
INSR	0.016	0.003	-9999	-10000	0	0
Insulin Receptor/Insulin	0.036	0.028	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.011	0.044	-9999	-0.56	3	3
SORBS1	0.011	0.046	-9999	-0.59	3	3
CRK	0.014	0	-9999	-10000	0	0
PTPN1	0.035	0.028	-9999	-10000	0	0
CAV1	-0.007	0.096	-9999	-0.37	6	6
CBL/APS/CAP/Crk-II/C3G	-0.009	0.053	-9999	-0.6	1	1
Insulin Receptor/Insulin/IRS1/NCK2	-0.003	0.027	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.003	0.026	-9999	-0.28	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.038	0.032	-9999	-10000	0	0
RPS6KB1	-0.029	0.12	-9999	-0.4	4	4
PARD6A	0.014	0	-9999	-10000	0	0
CBL	0.014	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	-0.001	0.038	-9999	-0.82	1	1
PIK3R1	0.014	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.064	0.088	-9999	-0.39	5	5
HRAS/GTP	-0.006	0.037	-9999	-0.42	1	1
Insulin Receptor	0.016	0.003	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.005	0.035	-9999	-10000	0	0
PRKCI	-0.022	0.053	-9999	-0.55	4	4
Insulin Receptor/Insulin/GRB14/PDK1	-0.082	0.11	-9999	-0.48	4	4
SHC1	0.009	0.049	-9999	-0.49	5	5
negative regulation of MAPKKK cascade	-0.001	0.035	-9999	-0.5	2	2
PI3K	-0.003	0.027	-9999	-0.29	1	1
NCK2	0.014	0	-9999	-10000	0	0
RHOQ	0.014	0	-9999	-10000	0	0
mol:H2O2	0	0.003	-9999	-10000	0	0
HRAS/GDP	0	0	-9999	-10000	0	0
AKT2	-0.04	0.13	-9999	-0.45	4	4
PRKCZ	-0.043	0.12	-9999	-0.59	20	20
SH2B2	-0.001	0.094	-9999	-0.56	14	14
SHC/SHIP	0.029	0.05	-9999	-0.34	4	4
F2RL2	-0.095	0.21	-9999	-0.51	107	107
TRIP10	0.007	0.065	-9999	-0.55	7	7
Insulin Receptor/Insulin/Shc	-0.005	0.038	-9999	-0.28	9	9
TC10/GTP/CIP4/Exocyst	-0.005	0.039	-9999	-0.33	7	7
Insulin Receptor/Insulin/SHC/GRB2/Sos1	-0.005	0.035	-9999	-10000	0	0
RAPGEF1	0.014	0	-9999	-10000	0	0
RASA1	0.014	0	-9999	-10000	0	0
NCK1	0.013	0.027	-9999	-0.59	1	1
CBL/APS/CAP/Crk-II	-0.01	0.057	-9999	-0.34	12	12
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	-0.007	0.044	-9999	-0.31	6	6
INPP5D	0.023	0.046	-9999	-0.32	7	7
SOS1	0.014	0	-9999	-10000	0	0
SGK1	-0.029	0.14	-9999	-0.88	14	14
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.014	0	-9999	-10000	0	0
IRS1	0.014	0	-9999	-10000	0	0
p62DOK/RasGAP	-0.001	0.036	-9999	-0.51	2	2
INS	-0.002	0.056	-9999	-0.57	5	5
mol:PI-3-4-P2	0.023	0.046	-9999	-0.32	7	7
GRB2	0.013	0.022	-9999	-0.49	1	1
EIF4EBP1	-0.035	0.13	-9999	-0.42	12	12
PTPRA	0.016	0.003	-9999	-10000	0	0
PIK3CA	0.013	0.027	-9999	-0.59	1	1
TC10/GTP/CIP4	-0.005	0.039	-9999	-0.33	7	7
PDPK1	0.012	0.038	-9999	-0.59	2	2
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.032	0.031	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1	-0.003	0.028	-9999	-0.3	4	4
Insulin Receptor/Insulin/IRS3	-0.004	0.04	-9999	-0.41	5	5
Par3/Par6	-0.054	0.1	-9999	-0.31	29	29

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.015	0.077	-9999	-0.32	19	19
PDGFB-D/PDGFRB/SLAP	-0.006	0.1	-9999	-0.4	32	32
PDGFB-D/PDGFRB/APS/CBL	-0.006	0.063	-9999	-0.35	16	16
AKT1	0.058	0.037	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.009	0.086	-9999	-0.36	11	11
PIK3CA	0.013	0.027	-9999	-0.59	1	1
FGR	0.001	0.028	-9999	-10000	0	0
mol:Ca2+	0.019	0.041	-9999	-10000	0	0
MYC	0.001	0.18	-9999	-0.8	23	23
SHC1	0.009	0.049	-9999	-0.49	5	5
HRAS/GDP	0.037	0.021	-9999	-10000	0	0
LRP1/PDGFRB/PDGFB	0.003	0.024	-9999	-0.28	3	3
GRB10	0.011	0.044	-9999	-0.56	3	3
PTPN11	0.014	0	-9999	-10000	0	0
GO:0007205	0.019	0.041	-9999	-10000	0	0
PTEN	0.013	0.027	-9999	-0.59	1	1
GRB2	0.013	0.022	-9999	-0.49	1	1
GRB7	-0.032	0.14	-9999	-0.49	43	43
PDGFB-D/PDGFRB/SHP2	0.017	0.028	-9999	-0.34	3	3
PDGFB-D/PDGFRB/GRB10	0.015	0.043	-9999	-0.37	6	6
cell cycle arrest	-0.006	0.1	-9999	-0.39	32	32
HRAS	0.014	0	-9999	-10000	0	0
HIF1A	0.063	0.041	-9999	-0.44	1	1
GAB1	0.007	0.072	-9999	-0.36	5	5
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.01	0.074	-9999	-0.36	5	5
PDGFB-D/PDGFRB	0.011	0.028	-9999	-0.29	3	3
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.017	0.028	-9999	-0.34	3	3
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.025	0.085	-9999	-0.41	12	12
positive regulation of MAPKKK cascade	0.017	0.028	-9999	-0.34	3	3
PIK3R1	0.014	0	-9999	-10000	0	0
mol:IP3	0.019	0.042	-9999	-10000	0	0
E5	0	0.001	-9999	-10000	0	0
CSK	0.014	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.015	0.1	-9999	-0.35	45	45
SHB	0.014	0	-9999	-10000	0	0
BLK	-0.054	0.14	-9999	-0.55	31	31
PTPN2	0.014	0.003	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.017	0.028	-9999	-0.34	3	3
BCAR1	0.013	0.027	-9999	-0.59	1	1
VAV2	0.008	0.087	-9999	-0.38	8	8
CBL	0.014	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.017	0.032	-9999	-0.34	4	4
LCK	-0.053	0.15	-9999	-0.52	41	41
PDGFRB	0.011	0.039	-9999	-0.49	3	3
ACP1	0.014	0	-9999	-10000	0	0
HCK	-0.01	0.091	-9999	-0.61	10	10
ABL1	0.008	0.062	-9999	-0.32	4	4
PDGFB-D/PDGFRB/CBL	0.007	0.07	-9999	-0.35	4	4
PTPN1	0.014	0.003	-9999	-10000	0	0
SNX15	0.014	0	-9999	-10000	0	0
STAT3	0.014	0	-9999	-10000	0	0
STAT1	-0.001	0.087	-9999	-0.49	16	16
cell proliferation	0.006	0.16	-9999	-0.7	23	23
SLA	-0.018	0.13	-9999	-0.54	30	30
actin cytoskeleton reorganization	0.048	0.032	-9999	-10000	0	0
SRC	0.003	0.026	-9999	-10000	0	0
PI3K	-0.005	0.031	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	-0.023	0.092	-9999	-0.3	48	48
SH2B2	-0.001	0.094	-9999	-0.56	14	14
PLCgamma1/SPHK1	0.009	0.088	-9999	-0.37	11	11
LYN	-0.001	0.051	-9999	-0.63	2	2
LRP1	0.014	0	-9999	-10000	0	0
SOS1	0.014	0	-9999	-10000	0	0
STAT5B	0.014	0	-9999	-10000	0	0
STAT5A	0.001	0.088	-9999	-0.59	11	11
NCK1-2/p130 Cas	0.008	0.031	-9999	-10000	0	0
SPHK1	-0.028	0.15	-9999	-0.54	40	40
EDG1	0	0.002	-9999	-10000	0	0
mol:DAG	0.019	0.042	-9999	-10000	0	0
PLCG1	0.019	0.042	-9999	-10000	0	0
NHERF/PDGFRB	-0.001	0.043	-9999	-0.32	9	9
YES1	-0.002	0.056	-9999	-0.55	4	4
cell migration	-0.004	0.042	-9999	-0.31	9	9
SHC/Grb2/SOS1	0.006	0.041	-9999	-0.45	2	2
SLC9A3R2	0.012	0.031	-9999	-0.49	2	2
SLC9A3R1	0.009	0.053	-9999	-0.59	4	4
NHERF1-2/PDGFRB/PTEN	0.006	0.044	-9999	-0.32	5	5
FYN	0.003	0.026	-9999	-10000	0	0
DOK1	0.032	0.03	-9999	-0.33	1	1
HRAS/GTP	0	0	-9999	-10000	0	0
PDGFB	0.014	0	-9999	-10000	0	0
RAC1	0.013	0.12	-9999	-0.44	24	24
PRKCD	0.015	0.083	-9999	-0.33	27	27
FER	0.018	0.075	-9999	-0.32	21	21
MAPKKK cascade	-0.004	0.034	-9999	-0.45	2	2
RASA1	0.033	0.023	-9999	-10000	0	0
NCK1	0.013	0.027	-9999	-0.59	1	1
NCK2	0.014	0	-9999	-10000	0	0
p62DOK/Csk	0.04	0.027	-9999	-0.3	1	1
PDGFB-D/PDGFRB/SHB	0.017	0.028	-9999	-0.34	3	3
chemotaxis	0.008	0.061	-9999	-0.31	4	4
STAT1-3-5/STAT1-3-5	-0.013	0.052	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0.008	0.028	-9999	-0.35	3	3
PTPRJ	0.013	0.022	-9999	-0.49	1	1

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	-0.002	0.028	-9999	-0.32	4	4
HDAC3	0.014	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC4	-0.005	0.039	-9999	-0.34	7	7
GATA1/HDAC5	-0.005	0.039	-9999	-0.34	7	7
GATA2/HDAC5	-0.012	0.07	-9999	-0.4	16	16
HDAC5/BCL6/BCoR	-0.001	0.012	-9999	-0.28	1	1
HDAC9	-0.002	0.094	-9999	-0.55	15	15
Glucocorticoid receptor/Hsp90/HDAC6	0	0	-9999	-10000	0	0
HDAC4/ANKRA2	0	0	-9999	-10000	0	0
HDAC5/YWHAB	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.024	0	-9999	-10000	0	0
GATA2	-0.004	0.1	-9999	-0.56	16	16
HDAC4/RFXANK	-0.001	0.015	-9999	-0.34	1	1
BCOR	0.013	0.022	-9999	-0.49	1	1
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.014	0	-9999	-10000	0	0
HDAC5	0.014	0	-9999	-10000	0	0
GNB1/GNG2	-0.003	0.038	-9999	-0.43	4	4
Histones	0.038	0.036	-9999	-10000	0	0
ADRBK1	0.014	0	-9999	-10000	0	0
HDAC4	0.014	0	-9999	-10000	0	0
XPO1	0.014	0	-9999	-10000	0	0
HDAC5/ANKRA2	0	0	-9999	-10000	0	0
HDAC4/Ubc9	0	0	-9999	-10000	0	0
HDAC7	0.014	0	-9999	-10000	0	0
HDAC5/14-3-3 E	0	0	-9999	-10000	0	0
TUBA1B	0.014	0	-9999	-10000	0	0
HDAC6	0.014	0	-9999	-10000	0	0
HDAC5/RFXANK	-0.001	0.015	-9999	-0.34	1	1
CAMK4	-0.18	0.27	-9999	-0.57	168	168
Tubulin/HDAC6	-0.001	0.016	-9999	-0.36	1	1
SUMO1	0.014	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.014	0	-9999	-10000	0	0
GATA1	0.004	0.058	-9999	-0.49	7	7
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.014	0	-9999	-10000	0	0
NR3C1	0.014	0	-9999	-10000	0	0
SUMO1/HDAC4	0.033	0	-9999	-10000	0	0
SRF	0.014	0	-9999	-10000	0	0
HDAC4/YWHAB	0	0	-9999	-10000	0	0
Tubulin	-0.001	0.019	-9999	-0.43	1	1
HDAC4/14-3-3 E	0	0	-9999	-10000	0	0
GNB1	0.014	0	-9999	-10000	0	0
RANGAP1	0.014	0	-9999	-10000	0	0
BCL6/BCoR	-0.001	0.015	-9999	-0.34	1	1
HDAC4/HDAC3/SMRT (N-CoR2)	0	0	-9999	-10000	0	0
HDAC4/SRF	-0.11	0.16	-9999	-0.36	125	125
HDAC4/ER alpha	-0.019	0.084	-9999	-0.38	26	26
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.038	0.036	-9999	-10000	0	0
cell motility	-0.001	0.016	-9999	-0.36	1	1
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.014	0	-9999	-10000	0	0
HDAC7/HDAC3	0	0	-9999	-10000	0	0
BCL6	0.014	0	-9999	-10000	0	0
HDAC4/CaMK II delta B	0.014	0	-9999	-10000	0	0
Hsp90/HDAC6	0	0	-9999	-10000	0	0
ESR1	-0.014	0.12	-9999	-0.54	26	26
HDAC6/HDAC11	-0.001	0.019	-9999	-0.43	1	1
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
MEF2C	-0.007	0.1	-9999	-0.5	21	21
RAN	0.014	0	-9999	-10000	0	0
HDAC4/MEF2C	-0.009	0.045	-9999	-10000	0	0
GNG2	0.009	0.053	-9999	-0.59	4	4
NCOR2	0.014	0	-9999	-10000	0	0
TUBB2A	0.013	0.027	-9999	-0.59	1	1
HDAC11	0.013	0.027	-9999	-0.59	1	1
HSP90AA1	0.014	0	-9999	-10000	0	0
RANBP2	0.014	0	-9999	-10000	0	0
ANKRA2	0.014	0	-9999	-10000	0	0
RFXANK	0.013	0.022	-9999	-0.49	1	1
nuclear import	-0.032	0	-9999	-10000	0	0

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.014	0	-10000	0	-10000	0	0
PTK2	0.014	0	-10000	0	-10000	0	0
CRKL	0.018	0.057	-10000	0	-0.28	15	15
GRB2/SOS1/SHC	-0.003	0.03	-10000	0	-0.28	6	6
HRAS	0.014	0	-10000	0	-10000	0	0
IRS1/Crk	0.018	0.056	-10000	0	-0.29	14	14
IGF-1R heterotetramer/IGF1/PTP1B	-0.012	0.061	-10000	0	-0.34	14	14
AKT1	0.038	0.057	-10000	0	-0.54	1	1
BAD	0.044	0.054	-10000	0	-0.5	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.018	0.056	-10000	0	-0.29	14	14
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.018	0.056	-10000	0	-0.29	14	14
RAF1	0.048	0.054	-10000	0	-0.52	1	1
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.025	0.055	-10000	0	-0.27	14	14
YWHAZ	0.014	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.009	0.061	-10000	0	-0.32	14	14
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
RPS6KB1	0.038	0.057	-10000	0	-0.54	1	1
GNB2L1	0.014	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	0.041	0.048	-10000	0	-0.44	1	1
PXN	0.014	0	-10000	0	-10000	0	0
PIK3R1	0.014	0	-10000	0	-10000	0	0
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	-0.001	0.015	-10000	0	-0.34	1	1
HRAS/GTP	-0.01	0.047	-10000	0	-0.36	2	2
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.012	0.055	-10000	0	-0.43	2	2
IGF-1R heterotetramer	0.011	0.025	-10000	0	-0.48	1	1
IGF-1R heterotetramer/IGF1/IRS/Nck	0.018	0.057	-10000	0	-0.29	14	14
Crk/p130 Cas/Paxillin	-0.009	0.045	-10000	0	-10000	0	0
IGF1R	0.011	0.025	-10000	0	-0.48	1	1
IGF1	-0.008	0.11	-10000	0	-0.56	20	20
IRS2/Crk	0.025	0.058	-10000	0	-0.28	15	15
PI3K	0.025	0.055	-10000	0	-0.27	15	15
apoptosis	-0.049	0.048	0.42	1	-10000	0	1
HRAS/GDP	0	0	-10000	0	-10000	0	0
PRKCD	0.015	0.12	-10000	0	-0.39	33	33
RAF1/14-3-3 E	0.053	0.049	-10000	0	-0.44	1	1
BAD/14-3-3	0.051	0.051	-10000	0	-0.45	1	1
PRKCZ	0.023	0.085	-10000	0	-0.46	3	3
Crk/p130 Cas/Paxillin/FAK1	-0.008	0.038	-10000	0	-0.44	1	1
PTPN1	0.014	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.024	0.075	-10000	0	-0.38	16	16
BCAR1	0.013	0.027	-10000	0	-0.59	1	1
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.015	0.065	-10000	0	-0.31	18	18
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.014	0	-10000	0	-10000	0	0
IRS1/NCK2	0.018	0.056	-10000	0	-0.29	14	14
GRB10	0.011	0.044	-10000	0	-0.56	3	3
PTPN11	0.018	0.056	-10000	0	-0.29	14	14
IRS1	0.01	0.061	-10000	0	-0.32	14	14
IRS2	0.017	0.061	-10000	0	-0.3	16	16
IGF-1R heterotetramer/IGF1	0.002	0.085	-10000	0	-0.41	21	21
GRB2	0.013	0.022	-10000	0	-0.49	1	1
PDPK1	0.031	0.059	-10000	0	-0.42	2	2
YWHAE	0.014	0	-10000	0	-10000	0	0
PRKD1	0.031	0.071	-10000	0	-0.37	14	14
SHC1	0.009	0.049	-10000	0	-0.49	5	5

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	0.024	0.016	-10000	0	-0.34	1	1
BAD/BCL-XL/YWHAZ	0.036	0.012	-10000	0	-10000	0	0
CDKN1B	0.04	0.009	-10000	0	-10000	0	0
CDKN1A	0.008	0.088	-10000	0	-0.28	20	20
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.014	0	-10000	0	-10000	0	0
FOXO3	0.04	0.009	-10000	0	-10000	0	0
AKT1	0	0.007	-10000	0	-10000	0	0
BAD	0.014	0	-10000	0	-10000	0	0
AKT3	0.013	0.061	-10000	0	-0.56	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.04	0.016	-10000	0	-0.28	1	1
AKT1/ASK1	0.034	0.038	-10000	0	-0.29	7	7
BAD/YWHAZ	0	0	-10000	0	-10000	0	0
RICTOR	0.014	0	-10000	0	-10000	0	0
RAF1	0.014	0	-10000	0	-10000	0	0
JNK cascade	0.004	0.033	0.28	7	-10000	0	7
TSC1	0.04	0.009	-10000	0	-10000	0	0
YWHAZ	0.014	0	-10000	0	-10000	0	0
AKT1/RAF1	0.04	0.009	-10000	0	-10000	0	0
EP300	0.009	0.053	-10000	0	-0.59	4	4
mol:GDP	0.033	0.009	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.04	0.009	-10000	0	-10000	0	0
YWHAQ	0.014	0	-10000	0	-10000	0	0
TBC1D4	0.025	0.02	-10000	0	-0.3	2	2
MAP3K5	0.006	0.07	-10000	0	-0.59	7	7
MAPKAP1	0.014	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.013	0.059	0.27	1	-10000	0	1
YWHAH	-0.01	0.11	-10000	0	-0.49	25	25
AKT1S1	0.04	0.009	-10000	0	-10000	0	0
CASP9	0.04	0.014	-10000	0	-10000	0	0
YWHAB	0.014	0	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.047	0.008	-10000	0	-10000	0	0
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	-0.001	0.022	-10000	0	-0.36	2	2
YWHAE	0.014	0	-10000	0	-10000	0	0
SRC	0.014	0	-10000	0	-10000	0	0
AKT2/p21CIP1	-0.026	0.072	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.02	0.003	-10000	0	-10000	0	0
CHUK	0.04	0.009	-10000	0	-10000	0	0
BAD/BCL-XL	0.054	0.013	-10000	0	-10000	0	0
mTORC2	0	0	-10000	0	-10000	0	0
AKT2	0.017	0.023	-10000	0	-0.35	2	2
FOXO1-3a-4/14-3-3 family	0.03	0.064	-10000	0	-0.29	1	1
PDPK1	0.012	0.038	-10000	0	-0.59	2	2
MDM2	0.039	0.018	-10000	0	-10000	0	0
MAPKKK cascade	-0.039	0.008	-10000	0	-10000	0	0
MDM2/Cbp/p300	0.05	0.035	-10000	0	-0.37	2	2
TSC1/TSC2	0.047	0.008	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.048	0.034	-10000	0	-0.35	2	2
glucose import	-0.011	0.11	-10000	0	-0.29	71	71
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.034	0.006	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.011	0.11	-10000	0	-0.29	71	71
GSK3A	0.04	0.009	-10000	0	-10000	0	0
FOXO1	0.038	0.024	-10000	0	-0.28	2	2
GSK3B	0.04	0.021	-10000	0	-0.41	1	1
SFN	-0.11	0.23	-10000	0	-0.53	119	119
G1/S transition of mitotic cell cycle	0.046	0.02	-10000	0	-0.39	1	1
p27Kip1/14-3-3 family	0.006	0.085	-10000	0	-0.39	3	3
PRKACA	0.014	0	-10000	0	-10000	0	0
KPNA1	0.014	0	-10000	0	-10000	0	0
HSP90AA1	0.014	0	-10000	0	-10000	0	0
YWHAG	0.002	0.079	-10000	0	-0.49	13	13
RHEB	0.014	0	-10000	0	-10000	0	0
CREBBP	0.014	0	-10000	0	-10000	0	0

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.015	0.16	-9999	-1.3	5	5
PLK1	0.048	0.22	-9999	-1	10	10
CDKN1B	0.098	0.11	-9999	-10000	0	0
FOXO3	0.063	0.16	-9999	-0.57	10	10
KAT2B	0.022	0.026	-9999	-0.47	1	1
FOXO1/SIRT1	-0.003	0.067	-9999	-0.41	5	5
CAT	0.066	0.16	-9999	-0.81	3	3
CTNNB1	0.014	0	-9999	-10000	0	0
AKT1	0.025	0.017	-9999	-10000	0	0
FOXO1	0.028	0.08	-9999	-0.45	5	5
MAPK10	0.037	0.034	-9999	-0.31	4	4
mol:GTP	0.002	0.002	-9999	-10000	0	0
FOXO4	0.094	0.068	-9999	-0.49	1	1
response to oxidative stress	0.01	0.02	-9999	-10000	0	0
FOXO3A/SIRT1	0.01	0.14	-9999	-0.56	8	8
XPO1	0.015	0.001	-9999	-10000	0	0
EP300	0.011	0.054	-9999	-0.59	4	4
BCL2L11	0.028	0.11	-9999	-1.4	3	3
FOXO1/SKP2	0.026	0.086	-9999	-0.43	9	9
mol:GDP	0.01	0.02	-9999	-10000	0	0
RAN	0.016	0.001	-9999	-10000	0	0
GADD45A	0.078	0.14	-9999	-0.67	3	3
YWHAQ	0.014	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.043	0.071	-9999	-10000	0	0
MST1	-0.017	0.15	-9999	-0.57	35	35
CSNK1D	0.014	0	-9999	-10000	0	0
CSNK1E	0.014	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.009	0.1	-9999	-0.42	2	2
YWHAB	0.014	0	-9999	-10000	0	0
MAPK8	0.032	0.058	-9999	-0.3	14	14
MAPK9	0.04	0.014	-9999	-10000	0	0
YWHAG	0.002	0.079	-9999	-0.49	13	13
YWHAE	0.014	0	-9999	-10000	0	0
YWHAZ	0.014	0	-9999	-10000	0	0
SIRT1	0.009	0.011	-9999	-10000	0	0
SOD2	0.093	0.16	-9999	-0.63	4	4
RBL2	0.083	0.13	-9999	-1.2	1	1
RAL/GDP	0.029	0.017	-9999	-10000	0	0
CHUK	0.023	0.014	-9999	-10000	0	0
Ran/GTP	0.014	0.005	-9999	-10000	0	0
CSNK1G2	0.014	0	-9999	-10000	0	0
RAL/GTP	0.037	0.019	-9999	-10000	0	0
CSNK1G1	0.013	0.022	-9999	-0.49	1	1
FASLG	0.005	0.099	-9999	-0.43	2	2
SKP2	0.005	0.07	-9999	-0.55	8	8
USP7	0.016	0.001	-9999	-10000	0	0
IKBKB	0.023	0.014	-9999	-10000	0	0
CCNB1	0.056	0.18	-9999	-0.7	6	6
FOXO1-3a-4/beta catenin	0.12	0.13	-9999	-0.42	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.026	0.086	-9999	-0.42	9	9
CSNK1A1	0.014	0	-9999	-10000	0	0
SGK1	0.005	0.1	-9999	-0.58	15	15
CSNK1G3	0.014	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.024	0.009	-9999	-10000	0	0
ZFAND5	0.096	0.061	-9999	-10000	0	0
SFN	-0.11	0.23	-9999	-0.53	119	119
CDK2	0.001	0.086	-9999	-0.53	13	13
FOXO3A/14-3-3	0.022	0.093	-9999	-0.43	1	1
CREBBP	0.014	0.012	-9999	-10000	0	0
FBXO32	0.054	0.19	-9999	-0.92	6	6
BCL6	0.085	0.12	-9999	-10000	0	0
RALB	0.015	0.001	-9999	-10000	0	0
RALA	0.015	0.001	-9999	-10000	0	0
YWHAH	-0.01	0.11	-9999	-0.49	25	25

×

Arf6 trafficking events

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
SLC2A4	-0.062	0.19	-10000	0	-0.55	69	69
CLTC	0.031	0.015	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.015	0.046	-10000	0	-10000	0	0
Dynamin 2/GTP	0.027	0	-10000	0	-10000	0	0
EXOC4	0.014	0	-10000	0	-10000	0	0
CD59	0.025	0.022	-10000	0	-10000	0	0
CPE	0.007	0.07	-10000	0	-0.36	18	18
CTNNB1	0.014	0	-10000	0	-10000	0	0
membrane fusion	0.014	0.049	-10000	0	-10000	0	0
CTNND1	0.035	0	-10000	0	-10000	0	0
DNM2	0.014	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.028	0.025	-10000	0	-10000	0	0
TSHR	-0.11	0.17	-10000	0	-0.33	196	196
INS	0.006	0.048	-10000	0	-0.52	4	4
BIN1	0.013	0.027	-10000	0	-0.59	1	1
mol:Choline	0.014	0.049	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.02	0	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.014	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
JUP	0.021	0.04	-10000	0	-0.29	4	4
ASAP2/amphiphysin II	-0.001	0.014	-10000	0	-0.33	1	1
ARF6/GTP	0	0	-10000	0	-10000	0	0
CDH1	-0.02	0.089	-10000	0	-0.29	13	13
clathrin-independent pinocytosis	0	0	-10000	0	-10000	0	0
MAPK8IP3	0.014	0	-10000	0	-10000	0	0
positive regulation of endocytosis	0	0	-10000	0	-10000	0	0
EXOC2	0.014	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.047	0.005	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.014	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.026	0.051	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.02	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0	0	-10000	0	-10000	0	0
ACAP1	0.012	0.044	-10000	0	-0.28	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	-0.022	0.087	-10000	0	-0.29	6	6
clathrin heavy chain/ACAP1	0.031	0.03	-10000	0	-10000	0	0
JIP4/KLC1	0	0	-10000	0	-10000	0	0
EXOC1	0.014	0	-10000	0	-10000	0	0
exocyst	0.047	0.006	-10000	0	-10000	0	0
RALA/GTP	0	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0	0	-10000	0	-10000	0	0
receptor recycling	0	0	-10000	0	-10000	0	0
CTNNA1	0.035	0	-10000	0	-10000	0	0
NME1	0.021	0	-10000	0	-10000	0	0
clathrin coat assembly	0.031	0.015	-10000	0	-10000	0	0
IL2RA	0.002	0.058	-10000	0	-0.29	1	1
VAMP3	0.021	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.036	0.083	-10000	0	-0.31	13	13
EXOC6	0.014	0	-10000	0	-10000	0	0
PLD1	-0.021	0.072	-10000	0	-0.28	34	34
PLD2	-0.001	0.012	-10000	0	-0.28	1	1
EXOC5	0.014	0	-10000	0	-10000	0	0
PIP5K1C	0.028	0.026	-10000	0	-10000	0	0
SDC1	0.012	0.049	-10000	0	-10000	0	0
ARF6/GDP	0.02	0	-10000	0	-10000	0	0
EXOC7	0.013	0.022	-10000	0	-0.49	1	1
E-cadherin/beta catenin	-0.027	0.052	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.014	0.049	-10000	0	-10000	0	0
endocytosis	0.001	0.014	0.32	1	-10000	0	1
SCAMP2	0.014	0	-10000	0	-10000	0	0
ADRB2	0.022	0.071	-10000	0	-0.29	24	24
EXOC3	0.014	0	-10000	0	-10000	0	0
ASAP2	0.014	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.028	0	-10000	0	-10000	0	0
KLC1	0.014	0	-10000	0	-10000	0	0
AVPR2	0.025	0.055	-10000	0	-10000	0	0
RALA	0.014	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.02	0.045	-10000	0	-10000	0	0

×

Arf6 downstream 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
PLAUR	0.016	0.12	-10000	0	-1.1	2	2
regulation of axonogenesis	-0.005	0.069	-10000	0	-10000	0	0
myoblast fusion	-0.004	0.06	0.41	2	-10000	0	2
mol:GTP	-0.01	0.034	-10000	0	-0.23	2	2
regulation of calcium-dependent cell-cell adhesion	-0.027	0.04	0.34	1	-10000	0	1
ARF1/GTP	-0.006	0.022	-10000	0	-10000	0	0
mol:GM1	0.004	0.028	-10000	0	-0.17	2	2
mol:Choline	-0.006	0.1	-10000	0	-0.32	45	45
lamellipodium assembly	-0.016	0.055	-10000	0	-0.45	2	2
MAPK3	0.018	0.054	-10000	0	-0.33	2	2
ARF6/GTP/NME1/Tiam1	0.028	0.041	-10000	0	-0.34	1	1
ARF1	0.014	0	-10000	0	-10000	0	0
ARF6/GDP	0.004	0.06	-10000	0	-0.41	2	2
ARF1/GDP	0.013	0.055	-10000	0	-0.37	2	2
ARF6	0.008	0.02	-10000	0	-10000	0	0
RAB11A	0.014	0	-10000	0	-10000	0	0
TIAM1	0.014	0.027	-10000	0	-0.59	1	1
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.018	0.054	-10000	0	-0.33	2	2
actin filament bundle formation	-0.013	0.055	0.37	2	-10000	0	2
KALRN	-0.018	0.058	-10000	0	-0.32	4	4
RAB11FIP3/RAB11A	0	0	-10000	0	-10000	0	0
RhoA/GDP	0.013	0.055	-10000	0	-0.38	2	2
NME1	0.015	0.004	-10000	0	-10000	0	0
Rac1/GDP	0.013	0.055	-10000	0	-0.38	2	2
substrate adhesion-dependent cell spreading	-0.01	0.034	-10000	0	-0.23	2	2
cortical actin cytoskeleton organization	-0.016	0.055	-10000	0	-0.45	2	2
RAC1	0.014	0	-10000	0	-10000	0	0
liver development	-0.01	0.034	-10000	0	-0.23	2	2
ARF6/GTP	-0.01	0.034	-10000	0	-0.23	2	2
RhoA/GTP	-0.006	0.022	-10000	0	-10000	0	0
mol:GDP	-0.016	0.054	-10000	0	-0.42	2	2
ARF6/GTP/RAB11FIP3/RAB11A	-0.004	0.017	-10000	0	-10000	0	0
RHOA	0.014	0	-10000	0	-10000	0	0
PLD1	-0.019	0.11	-10000	0	-0.38	44	44
RAB11FIP3	0.014	0	-10000	0	-10000	0	0
tube morphogenesis	-0.016	0.055	-10000	0	-0.45	2	2
ruffle organization	0.005	0.069	-10000	0	-10000	0	0
regulation of epithelial cell migration	-0.01	0.034	-10000	0	-0.23	2	2
PLD2	0.015	0.034	-10000	0	-0.4	1	1
PIP5K1A	0.005	0.069	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.006	0.1	-10000	0	-0.32	45	45
Rac1/GTP	-0.016	0.055	-10000	0	-0.45	2	2

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.014	0	-9999	-10000	0	0
SMAD2	0.016	0.017	-9999	-0.25	1	1
SMAD3	0.044	0.018	-9999	-10000	0	0
SMAD3/SMAD4	0.05	0.01	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	0	0	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	-0.001	0.014	-9999	-10000	0	0
PPM1A	0.014	0	-9999	-10000	0	0
CALM1	0.012	0.035	-9999	-0.54	2	2
SMAD2/SMAD4	0.023	0.015	-9999	-10000	0	0
MAP3K1	0.007	0.058	-9999	-0.49	7	7
TRAP-1/SMAD4	-0.014	0.076	-9999	-0.43	17	17
MAPK3	0.014	0	-9999	-10000	0	0
MAPK1	0.014	0	-9999	-10000	0	0
NUP214	0.014	0	-9999	-10000	0	0
CTDSP1	0.014	0	-9999	-10000	0	0
CTDSP2	0.01	0.044	-9999	-0.49	4	4
CTDSPL	0.013	0.027	-9999	-0.59	1	1
KPNB1	0.014	0	-9999	-10000	0	0
TGFBRAP1	-0.006	0.11	-9999	-0.59	17	17
UBE2I	0.014	0	-9999	-10000	0	0
NUP153	0.014	0	-9999	-10000	0	0
KPNA2	0.012	0.031	-9999	-0.49	2	2
PIAS4	0.014	0	-9999	-10000	0	0

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0	0	-9999	-10000	0	0
FBXW11	0.014	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.014	0	-9999	-10000	0	0
CHUK	0.014	0	-9999	-10000	0	0
NF kappa B2 p100/RelB	-0.004	0.034	-9999	-0.47	1	1
NFKB1	0.014	0	-9999	-10000	0	0
MAP3K14	0.014	0	-9999	-10000	0	0
NF kappa B1 p50/RelB	-0.003	0.035	-9999	-0.36	5	5
RELB	0.009	0.052	-9999	-0.51	5	5
NFKB2	0.011	0.044	-9999	-0.56	3	3
NF kappa B2 p52/RelB	-0.005	0.043	-9999	-0.36	7	7
regulation of B cell activation	-0.005	0.043	-9999	-0.36	7	7

×

mTOR signaling pathway

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
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.009	0.053	-10000	0	-0.59	4	4
mol:PIP3	0	0.018	0.29	1	-0.31	1	2
FRAP1	0.016	0.01	-10000	0	-10000	0	0
AKT1	0.03	0.026	0.23	1	-0.46	1	2
INSR	0.014	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	-0.003	0.035	-10000	0	-0.35	5	5
mol:GTP	-0.001	0.018	-10000	0	-0.37	1	1
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0	0.007	-10000	0	-10000	0	0
TSC2	0.014	0	-10000	0	-10000	0	0
RHEB/GDP	-0.001	0.016	-10000	0	-0.34	1	1
TSC1	0.014	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.018	0.001	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0	0.008	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.014	0	-10000	0	-10000	0	0
RPS6KB1	0.03	0.017	0.18	1	-0.28	1	2
MAP3K5	0.006	0.046	-10000	0	-0.39	7	7
PIK3R1	0.014	0	-10000	0	-10000	0	0
apoptosis	0.006	0.046	-10000	0	-0.39	7	7
mol:LY294002	0	0	0.001	1	-10000	0	1
EIF4B	0.036	0.016	-10000	0	-0.24	1	1
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.001	0.013	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	-0.002	0.016	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.026	0.015	-10000	0	-0.31	1	1
mTOR/RHEB/GTP/Raptor/GBL	0.034	0.014	0.17	1	-0.2	1	2
FKBP1A	0.014	0	-10000	0	-10000	0	0
RHEB/GTP	-0.001	0.016	-10000	0	-0.34	1	1
mol:Amino Acids	0	0	0.001	1	-10000	0	1
FKBP12/Rapamycin	0.011	0.001	-10000	0	-10000	0	0
PDPK1	-0.001	0.03	0.24	1	-0.42	2	3
EIF4E	0.014	0	-10000	0	-10000	0	0
ASK1/PP5C	0.015	0.073	-10000	0	-0.6	7	7
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.019	0.001	-10000	0	-10000	0	0
TSC1/TSC2	-0.001	0.019	-10000	0	-0.4	1	1
tumor necrosis factor receptor activity	0	0	-10000	0	-0.001	1	1
RPS6	0.013	0.022	-10000	0	-0.49	1	1
PPP5C	0.014	0	-10000	0	-10000	0	0
EIF4G1	0.014	0	-10000	0	-10000	0	0
IRS1	0.009	0.001	-10000	0	-10000	0	0
INS	-0.005	0.056	-10000	0	-0.57	5	5
PTEN	0.012	0.027	-10000	0	-0.59	1	1
PDK2	-0.001	0.021	0.24	1	-0.28	2	3
EIF4EBP1	-0.004	0.13	-10000	0	-1.1	7	7
PIK3CA	0.013	0.027	-10000	0	-0.6	1	1
PPP2R5D	0.023	0.009	-10000	0	-10000	0	0
peptide biosynthetic process	0.016	0.032	-10000	0	-0.31	5	5
RHEB	0.014	0	-10000	0	-10000	0	0
EIF4A1	0.014	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	0.004	1	-0.003	1	2
EEF2	0.016	0.032	-10000	0	-0.31	5	5
eIF4E/4E-BP1	0.005	0.12	-10000	0	-1	7	7

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.009	0.053	-9999	-0.59	4	4
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
MDM2/SUMO1	0.032	0.016	-9999	-0.22	2	2
HDAC4	0.014	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	-0.002	0.021	-9999	-0.24	4	4
SUMO1	0.014	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.019	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.031	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.014	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.014	0	-9999	-10000	0	0
SUMO1/HDAC4	0.033	0	-9999	-10000	0	0
SUMO1/HDAC1	0.031	0.028	-9999	-0.29	4	4
RANGAP1	0.014	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	-0.004	0.034	-9999	-0.32	5	5
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.024	0	-9999	-10000	0	0
Ran/GTP	0.029	0	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.012	0.031	-9999	-0.49	2	2
UBE2I	0.014	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.036	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
PIAS2	0.013	0.027	-9999	-0.59	1	1
PIAS1	0.009	0.053	-9999	-0.59	4	4
EntrezGene:9972	0	0	-9999	-10000	0	0

×

Arf1 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
coatomer protein complex	0	0.009	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.022	0.005	-9999	-10000	0	0
AP2	0	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0.001	-9999	-10000	0	0
CLTB	0.014	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.028	0	-9999	-10000	0	0
CD4	0.007	0.062	-9999	-0.52	7	7
CLTA	0.014	0	-9999	-10000	0	0
mol:GTP	0.002	0	-9999	-10000	0	0
ARFGAP1	0.012	0.016	-9999	-0.35	1	1
mol:PI-4-5-P2	0	0.008	-9999	-0.19	1	1
ARF1/GTP	0	0.004	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.029	0.011	-9999	-0.22	1	1
mol:Choline	0	0.009	-9999	-0.2	1	1
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.014	0	-9999	-10000	0	0
DDEF1	0	0.009	-9999	-0.2	1	1
ARF1/GDP	-0.001	0.011	-9999	-0.24	1	1
AP2M1	0.014	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0.018	0	-9999	-10000	0	0
Rac/GTP	0	0.001	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.027	0.012	-9999	-0.24	1	1
ARFIP2	0.012	0	-9999	-10000	0	0
COPA	0.014	0	-9999	-10000	0	0
RAC1	0.014	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.028	0.003	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0.001	-9999	-10000	0	0
GGA3	0.014	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0	0.002	-9999	-10000	0	0
AP2A1	0.014	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.03	0.007	-9999	-10000	0	0
ARF1/GDP/Membrin	0.02	0.004	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0	0.001	-9999	-10000	0	0
CYTH2	0.014	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0	0.001	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0	0	-9999	-10000	0	0
mol:Brefeldin A	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.037	0.02	-9999	-10000	0	0
PLD2	0	0.009	-9999	-0.2	1	1
ARF-GAP1/v-SNARE	0.012	0.016	-9999	-0.35	1	1
PIP5K1A	0	0.009	-9999	-0.19	1	1
ARF1/GTP/Membrin/GBF1/p115	0	0.004	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0.009	-9999	-0.2	1	1
KDEL Receptor/Ligand/ARF-GAP1	0.012	0.016	-9999	-0.35	1	1
GOSR2	0	0.004	-9999	-10000	0	0
USO1	0	0.004	-9999	-10000	0	0
GBF1	0	0.004	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	-0.004	0.035	-9999	-0.3	7	7

pid_entity	TCGA.WY.A85E	TCGA.WY.A85D	TCGA.WY.A85C	TCGA.WY.A85B
109_MAP3K5	0.059	-0.21	0.059	-0.21
47_PPARGC1A	0.014	0.014	0.014	0.014
105_BMP4	0.014	0.014	0.014	0.014
105_BMP6	0.014	0.014	0.014	0.014
105_BMP7	0.014	0.014	0.014	0.014
105_BMP2	0.014	0.014	0.014	0.014
131_RELN/VLDLR	0	0	-0.32	0
30_TGFB1/TGF beta receptor Type II	0.014	0.014	0.017	0.014
84_STAT5B	0.011	0.049	0.049	0.049
84_STAT5A	0.011	0.049	0.049	0.049