Skin Cutaneous Melanoma: PARADIGM pathway analysis of mRNASeq expression data<BR>(All

Pathway.Name	Avg.Num.Perturbations
TCGA08_retinoblastoma	76
Ephrin A reverse signaling	57
E-cadherin signaling events	55
Syndecan-1-mediated signaling events	52
TCR signaling in naïve CD8+ T cells	48
Signaling events mediated by Stem cell factor receptor (c-Kit)	45
IL4-mediated signaling events	41
Signaling events regulated by Ret tyrosine kinase	40
IL12-mediated signaling events	39
Wnt signaling	39

Pathway.Name	Avg.Num.Perturbations	Total.Perturbations	Num.Entities	Min.Mean.Truth	Max.Mean.Truth	Min.Mean.Within	Max.Mean.Within	Min.Mean.Any	Max.Mean.Within.1
TCGA08_retinoblastoma	76	610	8	-0.13	0.081	1000	-1000	-0.008	-1000
Ephrin A reverse signaling	57	400	7	-0.082	0	1000	-1000	-0.008	-1000
E-cadherin signaling events	55	277	5	-0.12	0.014	1000	-1000	-0.007	-1000
Syndecan-1-mediated signaling events	52	1773	34	-0.12	0.014	1000	-1000	-0.019	-1000
TCR signaling in naïve CD8+ T cells	48	4497	93	-0.23	0.02	1000	-1000	-0.041	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	45	3583	78	-0.26	0.1	1000	-1000	-0.035	-1000
IL4-mediated signaling events	41	3750	91	-0.64	0.5	1000	-1000	-0.14	-1000
Signaling events regulated by Ret tyrosine kinase	40	3325	82	-0.12	0.014	1000	-1000	-0.048	-1000
IL12-mediated signaling events	39	3478	87	-0.34	0.079	1000	-1000	-0.088	-1000
Wnt signaling	39	274	7	-0.078	-0.016	1000	-1000	-0.013	-1000
IL23-mediated signaling events	39	2391	60	-0.38	0.014	1000	-1000	-0.097	-1000
Glypican 1 network	38	1838	48	-0.14	0.033	1000	-1000	-0.024	-1000
Glypican 2 network	36	145	4	-0.029	-0.015	1000	-1000	-0.008	-1000
Glucocorticoid receptor regulatory network	34	3893	114	-0.4	0.28	1000	-1000	-0.04	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	34	2350	68	-0.33	0.1	1000	-1000	-0.061	-1000
Angiopoietin receptor Tie2-mediated signaling	34	3010	88	-0.21	0.042	1000	-1000	-0.059	-1000
BCR signaling pathway	33	3327	99	-0.19	0.014	1000	-1000	-0.054	-1000
p75(NTR)-mediated signaling	32	4097	125	-0.14	0.039	1000	-1000	-0.052	-1000
Stabilization and expansion of the E-cadherin adherens junction	32	2375	74	-0.12	0.041	1000	-1000	-0.047	-1000
E-cadherin signaling in the nascent adherens junction	32	2433	76	-0.12	0.022	1000	-1000	-0.045	-1000
E-cadherin signaling in keratinocytes	31	1358	43	-0.12	0.016	1000	-1000	-0.017	-1000
Noncanonical Wnt signaling pathway	30	790	26	-0.078	0.014	1000	-1000	-0.022	-1000
BMP receptor signaling	30	2499	81	-0.17	0.033	1000	-1000	-0.055	-1000
a4b1 and a4b7 Integrin signaling	29	148	5	-0.038	-0.017	1000	-1000	-0.006	-1000
Endothelins	29	2826	96	-0.14	0.037	1000	-1000	-0.045	-1000
LPA receptor mediated events	29	3057	102	-0.13	0.014	1000	-1000	-0.049	-1000
EGFR-dependent Endothelin signaling events	29	625	21	-0.097	0.02	1000	-1000	-0.035	-1000
Caspase cascade in apoptosis	28	2085	74	-0.091	0.047	1000	-1000	-0.016	-1000
TCGA08_p53	28	201	7	-0.096	0.066	1000	-1000	-0.005	-1000
FAS signaling pathway (CD95)	28	1329	47	-0.083	0.041	1000	-1000	-0.023	-1000
Calcium signaling in the CD4+ TCR pathway	28	869	31	-0.17	0.014	1000	-1000	-0.03	-1000
LPA4-mediated signaling events	26	322	12	-0.097	0.014	1000	-1000	-0.013	-1000
Signaling events mediated by the Hedgehog family	26	1352	52	-0.21	0.014	1000	-1000	-0.026	-1000
Nectin adhesion pathway	26	1661	63	-0.13	0.022	1000	-1000	-0.046	-1000
Signaling mediated by p38-alpha and p38-beta	26	1155	44	-0.095	0.014	1000	-1000	-0.015	-1000
Integrins in angiogenesis	26	2226	84	-0.13	0.02	1000	-1000	-0.05	-1000
Osteopontin-mediated events	23	884	38	-0.073	0.014	1000	-1000	-0.026	-1000
TRAIL signaling pathway	23	1121	48	-0.044	0.014	1000	-1000	-0.027	-1000
Class IB PI3K non-lipid kinase events	23	69	3	-0.021	-1000	1000	-1000	-0.006	-1000
JNK signaling in the CD4+ TCR pathway	22	387	17	-0.062	0.014	1000	-1000	-0.018	-1000
Thromboxane A2 receptor signaling	22	2337	105	-0.097	0.019	1000	-1000	-0.044	-1000
Syndecan-2-mediated signaling events	22	1569	69	-0.079	0.019	1000	-1000	-0.02	-1000
IL27-mediated signaling events	22	1140	51	-0.15	0.081	1000	-1000	-0.038	-1000
Syndecan-4-mediated signaling events	22	1516	67	-0.087	0.015	1000	-1000	-0.025	-1000
HIF-1-alpha transcription factor network	21	1670	76	-0.2	0.024	1000	-1000	-0.057	-1000
amb2 Integrin signaling	21	1735	82	-0.074	0.018	1000	-1000	-0.035	-1000
EPHB forward signaling	21	1805	85	-0.097	0.062	1000	-1000	-0.05	-1000
Arf6 signaling events	20	1241	62	-0.097	0.024	1000	-1000	-0.021	-1000
Signaling events mediated by PTP1B	20	1563	76	-0.12	0.032	1000	-1000	-0.039	-1000
Ephrin B reverse signaling	20	961	48	-0.068	0.014	1000	-1000	-0.036	-1000
Reelin signaling pathway	19	1099	56	-0.087	0.023	1000	-1000	-0.042	-1000
RXR and RAR heterodimerization with other nuclear receptor	18	969	52	-0.086	0.021	1000	-1000	-0.027	-1000
Effects of Botulinum toxin	18	488	26	-0.077	0.015	1000	-1000	-0.025	-1000
Neurotrophic factor-mediated Trk receptor signaling	18	2187	120	-0.14	0.13	1000	-1000	-0.041	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	17	1459	85	-0.056	0.014	1000	-1000	-0.042	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	17	785	45	-0.12	0.03	1000	-1000	-0.052	-1000
Ras signaling in the CD4+ TCR pathway	17	304	17	-0.048	0.027	1000	-1000	-0.011	-1000
PDGFR-alpha signaling pathway	16	719	44	-0.027	0.018	1000	-1000	-0.013	-1000
S1P4 pathway	16	405	25	-0.066	0.02	1000	-1000	-0.02	-1000
Fc-epsilon receptor I signaling in mast cells	15	1533	97	-0.078	0.025	1000	-1000	-0.047	-1000
S1P5 pathway	15	263	17	-0.066	0.031	1000	-1000	-0.017	-1000
Paxillin-independent events mediated by a4b1 and a4b7	14	528	37	-0.038	0.026	1000	-1000	-0.017	-1000
S1P1 pathway	14	536	36	-0.09	0.014	1000	-1000	-0.032	-1000
Signaling mediated by p38-gamma and p38-delta	14	217	15	-0.024	0.014	1000	-1000	-0.014	-1000
IL2 signaling events mediated by PI3K	14	840	58	-0.072	0.029	1000	-1000	-0.044	-1000
IL2 signaling events mediated by STAT5	14	324	22	-0.074	0.014	1000	-1000	-0.024	-1000
Plasma membrane estrogen receptor signaling	14	1288	86	-0.1	0.031	1000	-1000	-0.055	-1000
Ceramide signaling pathway	13	988	76	-0.097	0.047	1000	-1000	-0.016	-1000
Class I PI3K signaling events	13	997	73	-0.11	0.027	1000	-1000	-0.034	-1000
Rapid glucocorticoid signaling	13	272	20	-0.074	0.014	1000	-1000	-0.008	-1000
ErbB2/ErbB3 signaling events	12	792	65	-0.062	0.02	1000	-1000	-0.04	-1000
Cellular roles of Anthrax toxin	12	472	39	-0.036	0.014	1000	-1000	-0.014	-1000
FOXA2 and FOXA3 transcription factor networks	12	561	46	-0.25	0.013	1000	-1000	-0.079	-1000
IL1-mediated signaling events	12	749	62	-0.055	0.05	1000	-1000	-0.051	-1000
Visual signal transduction: Rods	12	649	52	-0.054	0.014	1000	-1000	-0.045	-1000
Coregulation of Androgen receptor activity	11	892	76	-0.14	0.029	1000	-1000	-0.02	-1000
Sphingosine 1-phosphate (S1P) pathway	11	320	28	-0.066	0.026	1000	-1000	-0.02	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	11	607	54	-0.087	0.024	1000	-1000	-0.053	-1000
Paxillin-dependent events mediated by a4b1	11	418	36	-0.038	0.032	1000	-1000	-0.033	-1000
Canonical Wnt signaling pathway	11	576	51	-0.11	0.047	1000	-1000	-0.032	-1000
ErbB4 signaling events	10	736	69	-0.15	0.1	1000	-1000	-0.055	-1000
Presenilin action in Notch and Wnt signaling	10	666	61	-0.11	0.044	1000	-1000	-0.033	-1000
Syndecan-3-mediated signaling events	10	366	35	-0.085	0.039	1000	-1000	-0.019	-1000
Nongenotropic Androgen signaling	10	529	52	-0.066	0.031	1000	-1000	-0.026	-1000
Regulation of nuclear SMAD2/3 signaling	9	1247	136	-0.17	0.046	1000	-1000	-0.026	-1000
Visual signal transduction: Cones	9	364	38	-0.038	0.013	1000	-1000	-0.014	-1000
IFN-gamma pathway	9	659	68	-0.083	0.026	1000	-1000	-0.055	-1000
Signaling events mediated by HDAC Class III	9	360	40	-0.11	0.024	1000	-1000	-0.009	-1000
Atypical NF-kappaB pathway	9	281	31	-0.075	0.024	1000	-1000	-0.016	-1000
Regulation of p38-alpha and p38-beta	9	526	54	-0.085	0.035	1000	-1000	-0.037	-1000
IGF1 pathway	9	545	57	-0.022	0.028	1000	-1000	-0.048	-1000
Signaling events mediated by PRL	9	310	34	-0.11	0.026	1000	-1000	-0.018	-1000
Regulation of Androgen receptor activity	9	672	70	-0.14	0.02	1000	-1000	-0.025	-1000
ceramide signaling pathway	8	396	49	-0.052	0.023	1000	-1000	-0.024	-1000
Retinoic acid receptors-mediated signaling	8	495	58	-0.06	0.028	1000	-1000	-0.041	-1000
TCGA08_rtk_signaling	8	221	26	-0.051	0.033	1000	-1000	-0.008	-1000
Regulation of Telomerase	8	818	102	-0.098	0.041	1000	-1000	-0.07	-1000
S1P3 pathway	8	340	42	-0.065	0.021	1000	-1000	-0.024	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	8	288	33	-0.14	0.037	1000	-1000	-0.018	-1000
FOXM1 transcription factor network	8	433	51	-0.14	0.13	1000	-1000	-0.13	-1000
Hedgehog signaling events mediated by Gli proteins	7	505	65	-0.066	0.055	1000	-1000	-0.043	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	7	650	83	-0.08	0.044	1000	-1000	-0.027	-1000
IL6-mediated signaling events	7	597	75	-0.046	0.052	1000	-1000	-0.034	-1000
Aurora B signaling	7	526	67	-0.096	0.032	1000	-1000	-0.03	-1000
PLK2 and PLK4 events	6	19	3	0.004	0.008	1000	-1000	-0.006	-1000
Insulin Pathway	6	509	74	-0.073	0.034	1000	-1000	-0.045	-1000
PDGFR-beta signaling pathway	6	640	97	-0.073	0.04	1000	-1000	-0.04	-1000
p38 MAPK signaling pathway	6	275	44	-0.041	0.026	1000	-1000	-0.039	-1000
Nephrin/Neph1 signaling in the kidney podocyte	5	195	34	-0.022	0.017	1000	-1000	-0.013	-1000
BARD1 signaling events	5	304	57	-0.021	0.045	1000	-1000	-0.028	-1000
EPO signaling pathway	5	292	55	-0.024	0.039	1000	-1000	-0.049	-1000
Signaling events mediated by VEGFR1 and VEGFR2	5	634	125	-0.068	0.044	1000	-1000	-0.049	-1000
Arf6 downstream pathway	4	193	43	-0.019	0.023	1000	-1000	-0.012	-1000
Aurora C signaling	4	34	7	-0.012	0.007	1000	-1000	-0.014	-1000
Insulin-mediated glucose transport	4	153	32	-0.08	0.026	1000	-1000	-0.023	-1000
mTOR signaling pathway	4	256	53	-0.01	0.023	1000	-1000	-0.035	-1000
FoxO family signaling	4	262	64	-0.2	0.11	1000	-1000	-0.037	-1000
Canonical NF-kappaB pathway	3	149	39	-0.021	0.055	1000	-1000	-0.047	-1000
Signaling events mediated by HDAC Class II	3	260	75	-0.059	0.035	1000	-1000	-0.022	-1000
Circadian rhythm pathway	3	73	22	-0.015	0.038	1000	-1000	-0.025	-1000
Aurora A signaling	3	182	60	-0.046	0.037	1000	-1000	-0.013	-1000
Arf6 trafficking events	3	275	71	-0.031	0.031	1000	-1000	-0.031	-1000
VEGFR1 specific signals	3	213	56	-0.019	0.029	1000	-1000	-0.028	-1000
PLK1 signaling events	2	186	85	-0.006	0.032	1000	-1000	-0.024	-1000
HIF-2-alpha transcription factor network	2	87	43	-0.14	0.14	1000	-1000	-0.055	-1000
Signaling events mediated by HDAC Class I	2	270	104	-0.027	0.045	1000	-1000	-0.022	-1000
Class I PI3K signaling events mediated by Akt	1	130	68	-0.08	0.041	1000	-1000	-0.018	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0	13	23	0.003	0.041	1000	-1000	-0.021	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0	11	27	-0.001	0.031	1000	-1000	-0.027	-1000
Arf1 pathway	0	26	54	0	0.025	1000	-1000	-0.013	-1000
Alternative NF-kappaB pathway	0	3	13	0	0.04	1000	-1000	-0.012	-1000
Total	2305	128738	7203	-13	-1000	131000	-131000	-4.3	-131000

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	-0.065	0.15	-10000	0	-0.37	57	57
CDKN2C	0.016	0.029	-10000	0	-0.4	1	1
CDKN2A	-0.13	0.19	-10000	0	-0.38	102	102
CCND2	0.071	0.12	0.23	88	-0.11	3	91
RB1	-0.075	0.14	-10000	0	-0.25	88	88
CDK4	0.081	0.14	0.26	88	-10000	0	88
CDK6	0.076	0.14	0.27	86	-0.14	9	95
G1/S progression	0.075	0.14	0.25	88	-10000	0	88

×

Ephrin A reverse signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.063	0.14	-9999	-0.27	79	79
EFNA5	-0.03	0.13	-9999	-0.42	28	28
FYN	-0.052	0.12	-9999	-0.25	73	73
neuron projection morphogenesis	-0.063	0.14	-9999	-0.27	79	79
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.064	0.14	-9999	-0.27	79	79
EPHA5	-0.082	0.18	-9999	-0.42	62	62

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.065	0.13	-9999	-0.25	80	80
E-cadherin/beta catenin	-0.079	0.14	-9999	-0.28	92	92
CTNNB1	0.014	0	-9999	-10000	0	0
JUP	-0.002	0.072	-9999	-0.32	13	13
CDH1	-0.12	0.2	-9999	-0.41	92	92

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.006	0.058	-9999	-0.43	5	5
CCL5	-0.059	0.15	-9999	-0.38	52	52
SDCBP	0.009	0.045	-9999	-0.43	3	3
FGFR/FGF2/Syndecan-1	-0.099	0.16	-9999	-0.28	94	94
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.095	0.16	-9999	-0.28	90	90
Syndecan-1/Syntenin	-0.091	0.16	-9999	-0.28	87	87
MAPK3	-0.071	0.14	-9999	-0.35	39	39
HGF/MET	-0.052	0.13	-9999	-0.26	72	72
TGFB1/TGF beta receptor Type II	0.006	0.058	-9999	-0.43	5	5
BSG	0.014	0	-9999	-10000	0	0
keratinocyte migration	-0.094	0.16	-9999	-0.28	90	90
Syndecan-1/RANTES	-0.12	0.19	-9999	-0.31	105	105
Syndecan-1/CD147	-0.079	0.15	-9999	-0.37	39	39
Syndecan-1/Syntenin/PIP2	-0.088	0.15	-9999	-0.27	87	87
LAMA5	-0.001	0.076	-9999	-0.39	10	10
positive regulation of cell-cell adhesion	-0.086	0.15	-9999	-0.26	87	87
MMP7	-0.067	0.15	-9999	-0.35	62	62
HGF	-0.025	0.11	-9999	-0.36	29	29
Syndecan-1/CASK	-0.095	0.15	-9999	-0.27	94	94
Syndecan-1/HGF/MET	-0.12	0.18	-9999	-0.39	67	67
regulation of cell adhesion	-0.064	0.14	-9999	-0.38	29	29
HPSE	-0.002	0.08	-9999	-0.42	10	10
positive regulation of cell migration	-0.099	0.16	-9999	-0.28	94	94
SDC1	-0.1	0.16	-9999	-0.28	94	94
Syndecan-1/Collagen	-0.099	0.16	-9999	-0.28	94	94
PPIB	0.014	0	-9999	-10000	0	0
MET	-0.051	0.15	-9999	-0.4	44	44
PRKACA	0.014	0	-9999	-10000	0	0
MMP9	-0.068	0.16	-9999	-0.38	59	59
MAPK1	-0.071	0.14	-9999	-0.35	39	39
homophilic cell adhesion	-0.098	0.16	-9999	-0.28	94	94
MMP1	-0.12	0.18	-9999	-0.36	99	99

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.12	0.28	-10000	0	-0.54	77	77
FYN	-0.18	0.39	-10000	0	-0.72	80	80
LAT/GRAP2/SLP76	-0.17	0.28	-10000	0	-0.55	82	82
IKBKB	0.014	0	-10000	0	-10000	0	0
AKT1	-0.097	0.23	-10000	0	-0.43	79	79
B2M	0.01	0.027	-10000	0	-0.44	1	1
IKBKG	-0.02	0.073	-10000	0	-0.14	60	60
MAP3K8	-0.004	0.08	-10000	0	-0.36	13	13
mol:Ca2+	-0.015	0.022	-10000	0	-0.069	20	20
integrin-mediated signaling pathway	0.006	0.052	-10000	0	-0.22	14	14
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.16	0.35	-10000	0	-0.66	80	80
TRPV6	-0.02	0.082	-10000	0	-0.31	20	20
CD28	-0.018	0.11	-10000	0	-0.39	22	22
SHC1	-0.18	0.38	-10000	0	-0.7	81	81
receptor internalization	-0.2	0.43	-10000	0	-0.75	85	85
PRF1	-0.21	0.46	-10000	0	-0.96	64	64
KRAS	0.012	0.019	-10000	0	-0.31	1	1
GRB2	0.014	0	-10000	0	-10000	0	0
COT/AKT1	-0.072	0.19	-10000	0	-0.35	75	75
LAT	-0.19	0.39	-10000	0	-0.7	84	84
EntrezGene:6955	-0.001	0.004	-10000	0	-10000	0	0
CD3D	-0.077	0.17	-10000	0	-0.39	64	64
CD3E	-0.071	0.17	-10000	0	-0.39	59	59
CD3G	-0.085	0.18	-10000	0	-0.39	69	69
RASGRP2	-0.01	0.038	-10000	0	-0.19	8	8
RASGRP1	-0.1	0.25	-10000	0	-0.48	76	76
HLA-A	0.003	0.06	-10000	0	-0.44	5	5
RASSF5	-0.006	0.088	-10000	0	-0.38	14	14
RAP1A/GTP/RAPL	0.007	0.052	-10000	0	-0.22	14	14
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	-0.011	0.069	-10000	0	-0.12	67	67
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.072	0.11	-10000	0	-0.24	70	70
PRKCA	-0.077	0.12	-10000	0	-0.26	74	74
GRAP2	-0.011	0.098	-10000	0	-0.39	17	17
mol:IP3	-0.12	0.21	0.16	14	-0.42	77	91
EntrezGene:6957	-0.002	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.21	0.45	-10000	0	-0.8	78	78
ORAI1	0.019	0.056	0.2	20	-0.3	2	22
CSK	-0.18	0.39	-10000	0	-0.72	81	81
B7 family/CD28	-0.18	0.4	-10000	0	-0.74	81	81
CHUK	0.012	0.026	-10000	0	-0.43	1	1
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.23	0.48	-10000	0	-0.82	87	87
PTPN6	-0.19	0.4	-10000	0	-0.74	80	80
VAV1	-0.19	0.4	-10000	0	-0.73	81	81
Monovalent TCR/CD3	-0.14	0.32	-10000	0	-0.56	80	80
CBL	0.014	0	-10000	0	-10000	0	0
LCK	-0.21	0.44	-10000	0	-0.81	80	80
PAG1	-0.19	0.4	-10000	0	-0.72	82	82
RAP1A	0.014	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.22	0.48	-10000	0	-0.86	80	80
CD80	-0.018	0.11	-10000	0	-0.38	22	22
CD86	-0.007	0.092	-10000	0	-0.43	13	13
PDK1/CARD11/BCL10/MALT1	-0.087	0.13	-10000	0	-0.28	75	75
HRAS	0.014	0	-10000	0	-10000	0	0
GO:0035030	-0.14	0.31	-10000	0	-0.58	81	81
CD8A	-0.086	0.18	-10000	0	-0.39	70	70
CD8B	-0.098	0.18	-10000	0	-0.4	77	77
PTPRC	-0.057	0.15	-10000	0	-0.39	49	49
PDK1/PKC theta	-0.13	0.29	-10000	0	-0.55	80	80
CSK/PAG1	-0.18	0.38	-10000	0	-0.71	79	79
SOS1	0.014	0	-10000	0	-10000	0	0
peptide-MHC class I	0.01	0.048	-10000	0	-0.31	6	6
GRAP2/SLP76	-0.17	0.36	-10000	0	-0.67	80	80
STIM1	0.011	0.025	-10000	0	-10000	0	0
RAS family/GTP	-0.016	0.094	-10000	0	-0.17	61	61
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.23	0.49	-10000	0	-0.84	85	85
mol:DAG	-0.11	0.18	-10000	0	-0.37	81	81
RAP1A/GDP	-0.003	0.031	-10000	0	-0.059	43	43
PLCG1	0.014	0	-10000	0	-10000	0	0
CD247	-0.056	0.15	-10000	0	-0.39	49	49
cytotoxic T cell degranulation	-0.2	0.42	-10000	0	-0.88	65	65
RAP1A/GTP	-0.006	0.012	-10000	0	-0.069	8	8
mol:PI-3-4-5-P3	-0.12	0.28	-10000	0	-0.52	80	80
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.16	0.28	0.18	14	-0.56	78	92
NRAS	0.014	0	-10000	0	-10000	0	0
ZAP70	-0.07	0.16	-10000	0	-0.37	61	61
GRB2/SOS1	0.02	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.17	0.27	-10000	0	-0.54	82	82
MALT1	0.01	0.037	-10000	0	-0.43	2	2
TRAF6	0.014	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.12	0.22	-10000	0	-0.44	85	85
CARD11	-0.061	0.16	-10000	0	-0.38	53	53
PRKCB	-0.09	0.14	-10000	0	-0.29	80	80
PRKCE	-0.076	0.12	-10000	0	-0.27	71	71
PRKCQ	-0.16	0.34	-10000	0	-0.64	81	81
LCP2	-0.015	0.11	-10000	0	-0.43	18	18
BCL10	0.012	0.019	-10000	0	-0.31	1	1
regulation of survival gene product expression	-0.078	0.19	-10000	0	-0.36	79	79
IKK complex	-0.007	0.064	-10000	0	-0.11	59	59
RAS family/GDP	-0.008	0.012	-10000	0	-10000	0	0
MAP3K14	-0.048	0.14	-10000	0	-0.27	70	70
PDPK1	-0.089	0.22	-10000	0	-0.41	78	78
TCR/CD3/MHC I/CD8/Fyn	-0.23	0.49	-10000	0	-0.88	82	82

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	-0.082	0.18	-10000	0	-0.38	65	65
CRKL	-0.075	0.18	-10000	0	-0.39	63	63
HRAS	-0.065	0.16	-10000	0	-0.33	69	69
mol:PIP3	-0.076	0.17	-10000	0	-0.37	62	62
SPRED1	0.004	0.064	-10000	0	-0.43	6	6
SPRED2	0.014	0	-10000	0	-10000	0	0
GAB1	-0.084	0.19	-10000	0	-0.41	64	64
FOXO3	-0.063	0.16	-10000	0	-0.36	61	61
AKT1	-0.074	0.18	-10000	0	-0.38	62	62
BAD	-0.064	0.17	-10000	0	-0.36	62	62
megakaryocyte differentiation	-0.089	0.18	-10000	0	-0.4	64	64
GSK3B	-0.063	0.16	-10000	0	-0.36	62	62
RAF1	-0.047	0.14	-10000	0	-0.27	69	69
SHC1	0.014	0	-10000	0	-10000	0	0
STAT3	-0.083	0.19	-10000	0	-0.41	63	63
STAT1	-0.2	0.42	-10000	0	-0.93	66	66
HRAS/SPRED1	-0.051	0.14	-10000	0	-0.27	71	71
cell proliferation	-0.083	0.19	-10000	0	-0.41	65	65
PIK3CA	0.007	0.052	-10000	0	-0.43	4	4
TEC	-0.005	0.089	-10000	0	-0.43	12	12
RPS6KB1	-0.081	0.19	-10000	0	-0.41	62	62
HRAS/SPRED2	-0.047	0.14	-10000	0	-0.27	66	66
LYN/TEC/p62DOK	-0.076	0.18	-10000	0	-0.39	64	64
MAPK3	-0.025	0.1	-10000	0	-0.19	65	65
STAP1	-0.12	0.2	-10000	0	-0.43	72	72
GRAP2	-0.011	0.098	-10000	0	-0.39	17	17
JAK2	-0.17	0.35	-10000	0	-0.79	66	66
STAT1 (dimer)	-0.19	0.41	-10000	0	-0.9	66	66
mol:Gleevec	0.002	0.007	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.087	0.18	-10000	0	-0.39	67	67
actin filament polymerization	-0.086	0.18	-10000	0	-0.4	63	63
LYN	0.012	0.026	-10000	0	-0.43	1	1
STAP1/STAT5A (dimer)	-0.15	0.26	-10000	0	-0.59	68	68
PIK3R1	0.01	0.037	-10000	0	-0.43	2	2
CBL/CRKL/GRB2	-0.056	0.17	-10000	0	-0.35	62	62
PI3K	-0.07	0.19	-10000	0	-0.39	64	64
PTEN	0.003	0.069	-10000	0	-0.43	7	7
SCF/KIT/EPO/EPOR	-0.24	0.49	-10000	0	-1.2	59	59
MAPK8	-0.085	0.19	-10000	0	-0.42	65	65
STAT3 (dimer)	-0.081	0.18	-10000	0	-0.4	63	63
positive regulation of transcription	-0.018	0.087	-10000	0	-0.16	65	65
mol:GDP	-0.073	0.17	-10000	0	-0.34	70	70
PIK3C2B	-0.083	0.19	-10000	0	-0.41	63	63
CBL/CRKL	-0.064	0.17	-10000	0	-0.37	63	63
FER	-0.086	0.19	-10000	0	-0.41	65	65
SH2B3	-0.085	0.18	-10000	0	-0.41	63	63
PDPK1	-0.066	0.16	-10000	0	-0.34	62	62
SNAI2	-0.09	0.19	-10000	0	-0.42	64	64
positive regulation of cell proliferation	-0.14	0.31	-10000	0	-0.69	66	66
KITLG	-0.003	0.072	-10000	0	-0.44	7	7
cell motility	-0.14	0.31	-10000	0	-0.69	66	66
PTPN6	-0.002	0.087	-10000	0	-0.38	14	14
EPOR	-0.036	0.13	-10000	0	-0.41	7	7
STAT5A (dimer)	-0.12	0.26	-10000	0	-0.58	66	66
SOCS1	0.003	0.064	-10000	0	-0.37	8	8
cell migration	0.1	0.19	0.41	69	-10000	0	69
SOS1	0.014	0	-10000	0	-10000	0	0
EPO	-0.006	0.062	-10000	0	-0.31	11	11
VAV1	-0.026	0.12	-10000	0	-0.42	26	26
GRB10	-0.087	0.19	-10000	0	-0.42	63	63
PTPN11	0.016	0.007	-10000	0	-10000	0	0
SCF/KIT	-0.092	0.2	-10000	0	-0.43	65	65
GO:0007205	0.004	0.01	-10000	0	-10000	0	0
MAP2K1	-0.031	0.11	-10000	0	-0.21	66	66
CBL	0.014	0	-10000	0	-10000	0	0
KIT	-0.26	0.51	-10000	0	-1.2	59	59
MAP2K2	-0.031	0.11	-10000	0	-0.21	65	65
SHC/Grb2/SOS1	-0.067	0.18	-10000	0	-0.38	62	62
STAT5A	-0.12	0.27	-10000	0	-0.59	66	66
GRB2	0.014	0	-10000	0	-10000	0	0
response to radiation	-0.088	0.19	-10000	0	-0.41	64	64
SHC/GRAP2	0.003	0.069	-10000	0	-0.27	17	17
PTPRO	-0.091	0.18	-10000	0	-0.41	64	64
SH2B2	-0.088	0.18	-10000	0	-0.41	63	63
DOK1	0.011	0.032	-10000	0	-0.37	2	2
MATK	-0.1	0.19	-10000	0	-0.42	68	68
CREBBP	0.004	0.049	-10000	0	-0.14	7	7
BCL2	-0.063	0.25	-10000	0	-1.4	8	8

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.44	0.47	-10000	0	-1.2	61	61
STAT6 (cleaved dimer)	-0.5	0.48	-10000	0	-1.1	94	94
IGHG1	-0.15	0.15	-10000	0	-0.38	2	2
IGHG3	-0.43	0.45	-10000	0	-1	76	76
AKT1	-0.27	0.33	-10000	0	-0.8	56	56
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.25	0.38	-10000	0	-0.9	50	50
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.28	0.36	-10000	0	-0.86	51	51
THY1	-0.44	0.48	-10000	0	-1.2	60	60
MYB	-0.004	0.082	-10000	0	-0.39	12	12
HMGA1	0.011	0.027	-10000	0	-0.31	2	2
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.34	0.4	-10000	0	-0.85	76	76
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.28	0.38	-10000	0	-0.91	50	50
SP1	0.019	0.008	-10000	0	-10000	0	0
INPP5D	-0.009	0.095	-10000	0	-0.39	16	16
SOCS5	0.023	0.04	-10000	0	-0.41	2	2
STAT6 (dimer)/ETS1	-0.46	0.5	-10000	0	-1.1	81	81
SOCS1	-0.3	0.32	-10000	0	-0.73	68	68
SOCS3	-0.28	0.34	-10000	0	-0.87	47	47
FCER2	-0.47	0.5	-10000	0	-1.2	64	64
PARP14	0.009	0.028	-10000	0	-0.43	1	1
CCL17	-0.49	0.54	-10000	0	-1.3	66	66
GRB2	0.014	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.22	0.28	-10000	0	-0.77	38	38
T cell proliferation	-0.46	0.5	-10000	0	-1.1	77	77
IL4R/JAK1	-0.44	0.48	-10000	0	-1.1	67	67
EGR2	-0.47	0.49	-10000	0	-1.2	63	63
JAK2	-0.025	0.073	-10000	0	-0.44	7	7
JAK3	-0.002	0.08	-10000	0	-0.38	12	12
PIK3R1	0.01	0.037	-10000	0	-0.43	2	2
JAK1	0.006	0.011	-10000	0	-10000	0	0
COL1A2	-0.18	0.3	-10000	0	-1.4	12	12
CCL26	-0.45	0.47	-10000	0	-1.2	61	61
IL4R	-0.47	0.51	-10000	0	-1.2	66	66
PTPN6	0.004	0.087	-10000	0	-0.37	14	14
IL13RA2	-0.64	0.6	-10000	0	-1.3	109	109
IL13RA1	-0.015	0.039	-10000	0	-0.47	1	1
IRF4	-0.3	0.5	-10000	0	-1.3	55	55
ARG1	-0.13	0.16	-10000	0	-0.65	8	8
CBL	-0.32	0.37	-10000	0	-0.82	71	71
GTF3A	0.018	0.013	-10000	0	-10000	0	0
PIK3CA	0.007	0.052	-10000	0	-0.43	4	4
IL13RA1/JAK2	-0.026	0.063	-10000	0	-0.31	8	8
IRF4/BCL6	-0.27	0.47	-10000	0	-1.2	54	54
CD40LG	-0.06	0.15	-10000	0	-0.38	50	50
MAPK14	-0.32	0.38	-10000	0	-0.86	66	66
mitosis	-0.25	0.31	-10000	0	-0.74	55	55
STAT6	-0.52	0.58	-10000	0	-1.3	68	68
SPI1	-0.007	0.09	-10000	0	-0.41	13	13
RPS6KB1	-0.24	0.3	-10000	0	-0.72	53	53
STAT6 (dimer)	-0.52	0.58	-10000	0	-1.3	68	68
STAT6 (dimer)/PARP14	-0.49	0.53	-10000	0	-1.2	71	71
mast cell activation	0.012	0.011	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.29	0.39	-10000	0	-0.94	51	51
FRAP1	-0.27	0.33	-10000	0	-0.8	56	56
LTA	-0.51	0.56	-10000	0	-1.3	74	74
FES	-0.002	0.082	-10000	0	-0.43	10	10
T-helper 1 cell differentiation	0.5	0.55	1.3	68	-10000	0	68
CCL11	-0.45	0.49	-10000	0	-1.2	67	67
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.29	0.39	-10000	0	-0.92	53	53
IL2RG	-0.043	0.14	-10000	0	-0.39	40	40
IL10	-0.46	0.51	-10000	0	-1.2	62	62
IRS1	-0.006	0.091	-10000	0	-0.42	13	13
IRS2	0.012	0.026	-10000	0	-0.43	1	1
IL4	-0.11	0.11	-10000	0	-10000	0	0
IL5	-0.45	0.47	-10000	0	-1.2	59	59
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.37	0.37	-10000	0	-0.9	62	62
COL1A1	-0.2	0.33	-10000	0	-1.4	15	15
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.45	0.49	-10000	0	-1.2	61	61
IL2R gamma/JAK3	-0.032	0.13	-10000	0	-0.34	40	40
TFF3	-0.56	0.57	-10000	0	-1.3	89	89
ALOX15	-0.45	0.48	-10000	0	-1.2	61	61
MYBL1	0.003	0.066	-10000	0	-0.41	7	7
T-helper 2 cell differentiation	-0.4	0.43	-10000	0	-0.96	79	79
SHC1	0.014	0	-10000	0	-10000	0	0
CEBPB	0.012	0.013	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.27	0.35	-10000	0	-0.85	51	51
mol:PI-3-4-5-P3	-0.27	0.33	-10000	0	-0.8	55	55
PI3K	-0.29	0.37	-10000	0	-0.88	55	55
DOK2	-0.001	0.078	-10000	0	-0.43	9	9
ETS1	0.024	0.021	-10000	0	-0.27	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.2	0.26	-10000	0	-0.72	38	38
ITGB3	-0.54	0.58	-10000	0	-1.3	84	84
PIGR	-0.49	0.53	-10000	0	-1.2	74	74
IGHE	0.04	0.046	0.24	6	-10000	0	6
MAPKKK cascade	-0.2	0.26	-10000	0	-0.7	38	38
BCL6	0.015	0.005	-10000	0	-10000	0	0
OPRM1	-0.45	0.47	-10000	0	-1.2	62	62
RETNLB	-0.45	0.47	-10000	0	-1.2	62	62
SELP	-0.54	0.58	-10000	0	-1.3	78	78
AICDA	-0.44	0.45	-10000	0	-1.1	61	61

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.012	0.045	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.072	0.1	-9999	-0.32	22	22
JUN	-0.049	0.12	-9999	-0.37	18	18
HRAS	0.014	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.09	0.15	-9999	-0.28	86	86
RAP1A	0.014	0	-9999	-10000	0	0
FRS2	0.011	0.027	-9999	-0.31	2	2
RAP1A/GDP	0.01	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.086	0.15	-9999	-0.27	84	84
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	-0.081	0.13	-9999	-0.21	124	124
RHOA	0.014	0	-9999	-10000	0	0
RAP1A/GTP	-0.075	0.13	-9999	-0.24	86	86
GRB7	-0.027	0.1	-9999	-0.31	33	33
RET51/GFRalpha1/GDNF	-0.085	0.14	-9999	-0.27	83	83
MAPKKK cascade	-0.082	0.11	-9999	-0.38	18	18
BCAR1	0.009	0.045	-9999	-0.43	3	3
RET9/GFRalpha1/GDNF/IRS1	-0.091	0.14	-9999	-0.22	131	131
lamellipodium assembly	-0.071	0.099	-9999	-0.22	69	69
RET51/GFRalpha1/GDNF/SHC	-0.085	0.14	-9999	-0.27	83	83
PIK3CA	0.007	0.052	-9999	-0.43	4	4
RET9/GFRalpha1/GDNF/SHC	-0.081	0.13	-9999	-0.21	124	124
RET9/GFRalpha1/GDNF/Shank3	-0.083	0.13	-9999	-0.26	82	82
MAPK3	-0.067	0.12	-9999	-0.31	33	33
DOK1	0.011	0.032	-9999	-0.37	2	2
DOK6	-0.049	0.14	-9999	-0.35	49	49
PXN	0.014	0	-9999	-10000	0	0
neurite development	-0.066	0.12	-9999	-0.3	35	35
DOK5	-0.066	0.15	-9999	-0.34	64	64
GFRA1	-0.089	0.17	-9999	-0.36	78	78
MAPK8	-0.057	0.13	-9999	-0.4	18	18
HRAS/GTP	-0.093	0.12	-9999	-0.43	18	18
tube development	-0.073	0.12	-9999	-0.24	78	78
MAPK1	-0.067	0.12	-9999	-0.31	33	33
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.056	0.11	-9999	-0.24	63	63
Rac1/GDP	0.01	0	-9999	-10000	0	0
SRC	0.012	0.026	-9999	-0.43	1	1
PDLIM7	0.014	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.1	0.16	-9999	-0.28	99	99
SHC1	0.014	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.087	0.15	-9999	-0.27	86	86
RET51/GFRalpha1/GDNF/Dok5	-0.12	0.16	-9999	-0.3	108	108
PRKCA	-0.004	0.084	-9999	-0.4	12	12
HRAS/GDP	0.01	0	-9999	-10000	0	0
CREB1	-0.056	0.13	-9999	-0.26	64	64
PIK3R1	0.01	0.037	-9999	-0.43	2	2
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.057	0.12	-9999	-0.24	64	64
RET51/GFRalpha1/GDNF/Grb7	-0.1	0.16	-9999	-0.29	91	91
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.01	0.089	-9999	-0.35	18	18
DOK4	0.009	0.045	-9999	-0.43	3	3
JNK cascade	-0.048	0.12	-9999	-0.36	18	18
RET9/GFRalpha1/GDNF/FRS2	-0.082	0.13	-9999	-0.26	80	80
SHANK3	0.009	0.045	-9999	-0.43	3	3
RASA1	0.009	0.045	-9999	-0.43	3	3
NCK1	0.014	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.055	0.11	-9999	-0.24	63	63
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.06	0.12	-9999	-0.24	68	68
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.063	0.13	-9999	-0.4	18	18
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.058	0.12	-9999	-0.24	68	68
PI3K	-0.077	0.17	-9999	-0.33	69	69
SOS1	0.014	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.071	0.12	-9999	-0.24	78	78
GRB10	0.004	0.064	-9999	-0.43	6	6
activation of MAPKK activity	-0.067	0.14	-9999	-0.32	44	44
RET51/GFRalpha1/GDNF/FRS2	-0.086	0.14	-9999	-0.27	84	84
GAB1	0.01	0.037	-9999	-0.43	2	2
IRS1	-0.006	0.091	-9999	-0.42	13	13
IRS2	0.012	0.026	-9999	-0.43	1	1
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.061	0.13	-9999	-0.25	68	68
RET51/GFRalpha1/GDNF/PKC alpha	-0.093	0.16	-9999	-0.29	88	88
GRB2	0.014	0	-9999	-10000	0	0
PRKACA	0.014	0	-9999	-10000	0	0
GDNF	-0.085	0.17	-9999	-0.38	70	70
RAC1	0.014	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.095	0.15	-9999	-0.28	93	93
Rac1/GTP	-0.082	0.12	-9999	-0.26	69	69
RET9/GFRalpha1/GDNF	-0.098	0.14	-9999	-0.24	124	124
GFRalpha1/GDNF	-0.12	0.17	-9999	-0.29	124	124

×

IL12-mediated 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.08	0.18	-10000	0	-0.38	50	50
TBX21	-0.28	0.58	-10000	0	-1.2	67	67
B2M	0.01	0.028	-10000	0	-0.43	1	1
TYK2	0.01	0.025	-10000	0	-10000	0	0
IL12RB1	-0.045	0.16	-10000	0	-0.43	38	38
GADD45B	-0.18	0.44	-10000	0	-0.95	55	55
IL12RB2	-0.082	0.18	-10000	0	-0.42	61	61
GADD45G	-0.22	0.51	-10000	0	-1.1	61	61
natural killer cell activation	0	0.025	-10000	0	-10000	0	0
RELB	0.014	0	-10000	0	-10000	0	0
RELA	0.014	0	-10000	0	-10000	0	0
IL18	-0.028	0.13	-10000	0	-0.41	29	29
IL2RA	-0.035	0.14	-10000	0	-0.4	33	33
IFNG	-0.085	0.17	-10000	0	-0.38	69	69
STAT3 (dimer)	-0.18	0.42	-10000	0	-0.8	74	74
HLA-DRB5	-0.04	0.14	-10000	0	-0.39	38	38
FASLG	-0.31	0.61	-10000	0	-1.2	78	78
NF kappa B2 p52/RelB	-0.3	0.49	-10000	0	-1	73	73
CD4	0.002	0.071	-10000	0	-0.41	8	8
SOCS1	0.003	0.064	-10000	0	-0.37	8	8
EntrezGene:6955	-0.001	0.011	-10000	0	-10000	0	0
CD3D	-0.077	0.17	-10000	0	-0.38	64	64
CD3E	-0.07	0.16	-10000	0	-0.38	59	59
CD3G	-0.085	0.17	-10000	0	-0.39	69	69
IL12Rbeta2/JAK2	-0.056	0.14	-10000	0	-0.3	66	66
CCL3	-0.25	0.54	-10000	0	-1.1	63	63
CCL4	-0.25	0.55	-10000	0	-1.1	66	66
HLA-A	0.004	0.059	-10000	0	-0.43	5	5
IL18/IL18R	-0.03	0.16	-10000	0	-0.3	64	64
NOS2	-0.24	0.53	-10000	0	-1.1	68	68
IL12/IL12R/TYK2/JAK2/SPHK2	-0.077	0.17	-10000	0	-0.37	48	48
IL1R1	-0.25	0.54	-10000	0	-1.1	67	67
IL4	0.001	0.032	-10000	0	-0.32	1	1
JAK2	-0.001	0.072	-10000	0	-0.42	7	7
EntrezGene:6957	-0.001	0.011	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.24	0.5	-10000	0	-0.95	75	75
RAB7A	-0.14	0.37	-10000	0	-0.8	52	52
lysosomal transport	-0.13	0.35	-10000	0	-0.74	54	54
FOS	-0.17	0.41	-10000	0	-0.98	48	48
STAT4 (dimer)	-0.21	0.48	-10000	0	-0.91	77	77
STAT5A (dimer)	-0.33	0.5	-10000	0	-1	81	81
GZMA	-0.28	0.59	-10000	0	-1.2	69	69
GZMB	-0.28	0.59	-10000	0	-1.2	70	70
HLX	0.01	0.037	-10000	0	-0.43	2	2
LCK	-0.31	0.63	-10000	0	-1.2	79	79
TCR/CD3/MHC II/CD4	-0.16	0.39	-10000	0	-0.71	69	69
IL2/IL2R	-0.054	0.18	-10000	0	-0.38	51	51
MAPK14	-0.2	0.48	-10000	0	-0.98	62	62
CCR5	-0.22	0.51	-10000	0	-1	64	64
IL1B	-0.051	0.15	-10000	0	-0.38	45	45
STAT6	-0.037	0.13	-10000	0	-0.25	41	41
STAT4	-0.033	0.13	-10000	0	-0.38	34	34
STAT3	0.014	0	-10000	0	-10000	0	0
STAT1	0.012	0.026	-10000	0	-0.43	1	1
NFKB1	0.014	0	-10000	0	-10000	0	0
NFKB2	0.014	0	-10000	0	-10000	0	0
IL12B	0.002	0.059	-10000	0	-0.33	7	7
CD8A	-0.086	0.17	-10000	0	-0.38	70	70
CD8B	-0.097	0.18	-10000	0	-0.39	77	77
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.079	0.18	0.38	50	-10000	0	50
IL2RB	-0.034	0.13	-10000	0	-0.38	34	34
proteasomal ubiquitin-dependent protein catabolic process	-0.18	0.42	-10000	0	-0.8	77	77
IL2RG	-0.045	0.15	-10000	0	-0.4	40	40
IL12	-0.016	0.11	-10000	0	-0.28	33	33
STAT5A	0.012	0.026	-10000	0	-0.43	1	1
CD247	-0.056	0.15	-10000	0	-0.38	49	49
IL2	0.001	0.027	-10000	0	-0.31	2	2
SPHK2	0.01	0.037	-10000	0	-0.43	2	2
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.032	0.13	-10000	0	-0.41	29	29
IL12/IL12R/TYK2/JAK2	-0.34	0.77	-10000	0	-1.4	73	73
MAP2K3	-0.2	0.48	-10000	0	-0.95	67	67
RIPK2	0.014	0	-10000	0	-10000	0	0
MAP2K6	-0.21	0.49	-10000	0	-0.97	66	66
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.029	0.13	-10000	0	-0.4	29	29
IL18RAP	-0.029	0.12	-10000	0	-0.37	32	32
IL12Rbeta1/TYK2	-0.024	0.12	-10000	0	-0.32	38	38
EOMES	-0.1	0.34	-10000	0	-1.2	23	23
STAT1 (dimer)	-0.22	0.43	-10000	0	-0.82	79	79
T cell proliferation	-0.12	0.34	-10000	0	-0.64	72	72
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.025	0.12	-10000	0	-0.39	28	28
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.21	0.32	-10000	0	-0.7	74	74
ATF2	-0.17	0.43	-10000	0	-0.87	62	62

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.078	0.14	-9999	-0.26	91	91
FZD6	-0.021	0.12	-9999	-0.43	22	22
WNT6	-0.016	0.099	-9999	-0.34	23	23
WNT4	-0.063	0.16	-9999	-0.38	54	54
FZD3	0.012	0.026	-9999	-0.43	1	1
WNT5A	-0.044	0.14	-9999	-0.37	42	42
WNT11	-0.041	0.14	-9999	-0.36	41	41

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.28	0.48	-10000	0	-1.1	57	57
IL23A	-0.3	0.5	-10000	0	-1.2	57	57
NF kappa B1 p50/RelA/I kappa B alpha	-0.33	0.47	-10000	0	-1.1	58	58
positive regulation of T cell mediated cytotoxicity	-0.34	0.58	-10000	0	-1.3	62	62
ITGA3	-0.32	0.52	-10000	0	-1.1	70	70
IL17F	-0.18	0.32	-10000	0	-0.7	58	58
IL12B	-0.007	0.06	-10000	0	-0.33	7	7
STAT1 (dimer)	-0.32	0.55	-10000	0	-1.2	62	62
CD4	-0.28	0.49	-10000	0	-1.1	56	56
IL23	-0.29	0.48	-10000	0	-1.1	56	56
IL23R	-0.033	0.089	-10000	0	-10000	0	0
IL1B	-0.32	0.55	-10000	0	-1.2	61	61
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.34	0.54	-10000	0	-1.2	68	68
TYK2	0.004	0.022	-10000	0	-10000	0	0
STAT4	-0.033	0.13	-10000	0	-0.38	34	34
STAT3	0.014	0	-10000	0	-10000	0	0
IL18RAP	-0.033	0.12	-10000	0	-0.36	32	32
IL12RB1	-0.052	0.15	-10000	0	-0.43	38	38
PIK3CA	0.007	0.052	-10000	0	-0.43	4	4
IL12Rbeta1/TYK2	-0.034	0.11	-10000	0	-0.31	38	38
IL23R/JAK2	-0.042	0.12	-10000	0	-10000	0	0
positive regulation of chronic inflammatory response	-0.34	0.58	-10000	0	-1.3	62	62
natural killer cell activation	0.004	0.008	0.033	2	-10000	0	2
JAK2	-0.006	0.074	-10000	0	-0.43	7	7
PIK3R1	0.01	0.037	-10000	0	-0.43	2	2
NFKB1	0.012	0.003	-10000	0	-10000	0	0
RELA	0.012	0.003	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.27	0.46	-10000	0	-1	56	56
ALOX12B	-0.29	0.48	-10000	0	-1.1	57	57
CXCL1	-0.34	0.53	-10000	0	-1.2	70	70
T cell proliferation	-0.34	0.58	-10000	0	-1.3	62	62
NFKBIA	0.012	0.003	-10000	0	-10000	0	0
IL17A	-0.13	0.26	-10000	0	-0.56	50	50
PI3K	-0.32	0.51	-10000	0	-1.2	58	58
IFNG	-0.03	0.052	-10000	0	-0.12	53	53
STAT3 (dimer)	-0.33	0.46	-10000	0	-1.1	57	57
IL18R1	-0.029	0.12	-10000	0	-0.38	28	28
IL23/IL23R/JAK2/TYK2/SOCS3	-0.17	0.31	-10000	0	-0.69	52	52
IL18/IL18R	-0.053	0.14	-10000	0	-0.29	61	61
macrophage activation	-0.017	0.018	-10000	0	-0.043	59	59
TNF	-0.31	0.53	-10000	0	-1.2	58	58
STAT3/STAT4	-0.34	0.51	-10000	0	-1.2	61	61
STAT4 (dimer)	-0.34	0.56	-10000	0	-1.2	61	61
IL18	-0.032	0.12	-10000	0	-0.4	29	29
IL19	-0.28	0.48	-10000	0	-1.1	56	56
STAT5A (dimer)	-0.32	0.55	-10000	0	-1.2	62	62
STAT1	0.012	0.026	-10000	0	-0.43	1	1
SOCS3	0.003	0.066	-10000	0	-0.41	7	7
CXCL9	-0.38	0.6	-10000	0	-1.3	71	71
MPO	-0.31	0.5	-10000	0	-1.1	64	64
positive regulation of humoral immune response	-0.34	0.58	-10000	0	-1.3	62	62
IL23/IL23R/JAK2/TYK2	-0.38	0.69	-10000	0	-1.5	61	61
IL6	-0.3	0.5	-10000	0	-1.1	58	58
STAT5A	0.012	0.026	-10000	0	-0.43	1	1
IL2	-0.001	0.029	-10000	0	-0.3	2	2
positive regulation of tyrosine phosphorylation of STAT protein	0.004	0.008	0.033	2	-10000	0	2
CD3E	-0.33	0.55	-10000	0	-1.3	57	57
keratinocyte proliferation	-0.34	0.58	-10000	0	-1.3	62	62
NOS2	-0.31	0.5	-10000	0	-1.1	62	62

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	-0.065	0.14	-10000	0	-0.25	94	94
fibroblast growth factor receptor signaling pathway	-0.065	0.14	-10000	0	-0.25	94	94
LAMA1	-0.079	0.17	-10000	0	-0.39	65	65
PRNP	0.009	0.042	-10000	0	-0.39	3	3
GPC1/SLIT2	-0.044	0.12	-10000	0	-0.27	63	63
SMAD2	0.001	0.071	-10000	0	-0.21	23	23
GPC1/PrPc/Cu2+	-0.012	0.082	-10000	0	-0.23	35	35
GPC1/Laminin alpha1	-0.077	0.15	-10000	0	-0.29	88	88
TDGF1	-0.001	0.045	-10000	0	-0.31	6	6
CRIPTO/GPC1	-0.023	0.096	-10000	0	-0.26	39	39
APP/GPC1	-0.032	0.12	-10000	0	-0.29	47	47
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.017	0.086	-10000	0	-0.24	27	27
FLT1	0.009	0.042	-10000	0	-0.39	3	3
GPC1/TGFB/TGFBR1/TGFBR2	-0.002	0.081	-10000	0	-0.24	23	23
SERPINC1	0.006	0.038	-10000	0	-0.31	4	4
FYN	-0.012	0.08	-10000	0	-0.24	22	22
FGR	-0.024	0.093	-10000	0	-0.25	33	33
positive regulation of MAPKKK cascade	-0.063	0.14	-10000	0	-0.33	46	46
SLIT2	-0.032	0.12	-10000	0	-0.36	34	34
GPC1/NRG	-0.064	0.14	-10000	0	-0.27	82	82
NRG1	-0.062	0.15	-10000	0	-0.35	57	57
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.011	0.09	-10000	0	-0.25	27	27
LYN	-0.013	0.081	-10000	0	-0.24	23	23
mol:Spermine	-0.023	0.092	-10000	0	-0.27	33	33
cell growth	-0.065	0.14	-10000	0	-0.25	94	94
BMP signaling pathway	0.033	0.13	0.39	33	-10000	0	33
SRC	-0.013	0.081	-10000	0	-0.24	23	23
TGFBR1	0.012	0.026	-10000	0	-0.43	1	1
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.14	0.19	-10000	0	-0.36	111	111
GPC1	-0.033	0.13	-10000	0	-0.39	33	33
TGFBR1 (dimer)	0.012	0.026	-10000	0	-0.43	1	1
VEGFA	0.001	0.064	-10000	0	-0.32	11	11
BLK	-0.069	0.12	-10000	0	-0.27	61	61
HCK	-0.022	0.092	-10000	0	-0.25	33	33
FGF2	-0.076	0.18	-10000	0	-0.42	59	59
FGFR1	-0.006	0.082	-10000	0	-0.35	15	15
VEGFR1 homodimer	0.009	0.042	-10000	0	-0.39	3	3
TGFBR2	0.012	0.019	-10000	0	-0.31	1	1
cell death	-0.031	0.12	-10000	0	-0.29	47	47
ATIII/GPC1	-0.019	0.095	-10000	0	-0.26	37	37
PLA2G2A/GPC1	-0.12	0.15	-10000	0	-0.26	138	138
LCK	-0.064	0.12	-10000	0	-0.26	63	63
neuron differentiation	-0.064	0.14	-10000	0	-0.27	82	82
PrPc/Cu2+	0.007	0.029	-10000	0	-0.27	3	3
APP	-0.013	0.1	-10000	0	-0.43	17	17
TGFBR2 (dimer)	0.012	0.019	-10000	0	-0.31	1	1

×

Glypican 2 network

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
MDK	-0.028	0.12	-9999	-0.39	29	29
GPC2	-0.015	0.1	-9999	-0.39	20	20
GPC2/Midkine	-0.029	0.11	-9999	-0.27	48	48
neuron projection morphogenesis	-0.029	0.11	-9999	-0.27	48	48

×

Glucocorticoid receptor regulatory network

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
PCK2	0.032	0.074	0.27	12	-10000	0	12
SMARCC2	0.014	0.011	-10000	0	-10000	0	0
SMARCC1	0.014	0.011	-10000	0	-10000	0	0
TBX21	-0.15	0.26	-10000	0	-0.53	71	71
SUMO2	0.017	0.01	-10000	0	-10000	0	0
STAT1 (dimer)	0.015	0.041	-10000	0	-0.28	5	5
FKBP4	0.014	0	-10000	0	-10000	0	0
FKBP5	-0.028	0.13	-10000	0	-0.42	27	27
GR alpha/HSP90/FKBP51/HSP90	0.083	0.11	0.23	43	-0.25	8	51
PRL	-0.084	0.12	-10000	0	-0.55	3	3
cortisol/GR alpha (dimer)/TIF2	0.24	0.22	0.48	106	-0.34	2	108
RELA	-0.015	0.068	-10000	0	-0.22	8	8
FGG	0.18	0.19	0.42	73	-0.32	3	76
GR beta/TIF2	0.11	0.12	0.26	66	-0.34	7	73
IFNG	-0.36	0.42	-10000	0	-0.84	92	92
apoptosis	0.083	0.16	0.5	25	-10000	0	25
CREB1	0.013	0.013	-10000	0	-10000	0	0
histone acetylation	-0.024	0.14	0.31	9	-0.29	29	38
BGLAP	-0.079	0.12	-10000	0	-0.37	16	16
GR/PKAc	0.11	0.1	0.25	48	-0.3	5	53
NF kappa B1 p50/RelA	-0.021	0.12	-10000	0	-0.33	15	15
SMARCD1	0.014	0.011	-10000	0	-10000	0	0
MDM2	0.091	0.085	0.2	73	-0.15	1	74
GATA3	-0.058	0.16	-10000	0	-0.4	51	51
AKT1	0.007	0.001	-10000	0	-10000	0	0
CSF2	-0.06	0.12	-10000	0	-0.46	3	3
GSK3B	0.017	0.01	-10000	0	-10000	0	0
NR1I3	0.091	0.15	0.48	24	-10000	0	24
CSN2	0.16	0.15	0.36	66	-10000	0	66
BRG1/BAF155/BAF170/BAF60A	0.037	0.038	-10000	0	-0.3	3	3
NFATC1	0.002	0.074	-10000	0	-0.43	8	8
POU2F1	0.012	0.017	-10000	0	-10000	0	0
CDKN1A	-0.02	0.23	-10000	0	-1.3	8	8
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.003	0.01	-10000	0	-10000	0	0
SFN	-0.08	0.15	-10000	0	-0.33	77	77
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.047	0.13	0.22	34	-0.28	16	50
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	0.08	0.16	0.46	24	-0.65	2	26
JUN	-0.19	0.17	-10000	0	-0.38	94	94
IL4	-0.1	0.14	-10000	0	-0.45	19	19
CDK5R1	0.004	0.069	-10000	0	-0.43	7	7
PRKACA	0.014	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.11	0.19	0.2	26	-0.34	79	105
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.088	0.1	0.23	42	-0.27	4	46
cortisol/GR alpha (monomer)	0.28	0.26	0.56	108	-10000	0	108
NCOA2	0	0.076	-10000	0	-0.42	9	9
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.057	0.075	-10000	0	-0.37	7	7
AP-1/NFAT1-c-4	-0.3	0.28	-10000	0	-0.55	125	125
AFP	-0.13	0.12	-10000	0	-0.48	2	2
SUV420H1	0.012	0.026	-10000	0	-0.43	1	1
IRF1	0.14	0.17	0.39	33	-0.63	5	38
TP53	0.012	0.097	-10000	0	-0.46	11	11
PPP5C	0.014	0	-10000	0	-10000	0	0
KRT17	-0.34	0.38	-10000	0	-0.72	102	102
KRT14	-0.33	0.45	-10000	0	-1.1	63	63
TBP	0.02	0.014	-10000	0	-10000	0	0
CREBBP	0.076	0.1	0.28	47	-0.24	2	49
HDAC1	0.011	0.026	-10000	0	-0.43	1	1
HDAC2	0.013	0.005	-10000	0	-10000	0	0
AP-1	-0.3	0.28	-10000	0	-0.55	127	127
MAPK14	0.016	0.009	-10000	0	-10000	0	0
MAPK10	-0.039	0.13	-10000	0	-0.34	43	43
MAPK11	0.01	0.052	-10000	0	-0.41	4	4
KRT5	-0.4	0.44	-10000	0	-0.88	104	104
interleukin-1 receptor activity	-0.001	0.005	-10000	0	-10000	0	0
NCOA1	0.016	0.001	-10000	0	-10000	0	0
STAT1	0.015	0.041	-10000	0	-0.27	5	5
CGA	-0.094	0.12	-10000	0	-0.4	12	12
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.15	0.14	0.34	69	-10000	0	69
MAPK3	0.017	0.01	-10000	0	-10000	0	0
MAPK1	0.016	0.009	-10000	0	-10000	0	0
ICAM1	-0.13	0.22	-10000	0	-0.57	36	36
NFKB1	-0.015	0.068	-10000	0	-0.22	8	8
MAPK8	-0.16	0.15	-10000	0	-0.34	88	88
MAPK9	0.016	0.009	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.079	0.16	0.5	25	-10000	0	25
BAX	0.008	0.074	-10000	0	-0.52	1	1
POMC	-0.23	0.39	-10000	0	-1.3	28	28
EP300	0.076	0.1	0.28	47	-0.24	2	49
cortisol/GR alpha (dimer)/p53	0.24	0.22	0.48	99	-10000	0	99
proteasomal ubiquitin-dependent protein catabolic process	0.064	0.066	0.18	37	-10000	0	37
SGK1	0.11	0.19	-10000	0	-1.1	4	4
IL13	-0.24	0.26	-10000	0	-0.63	65	65
IL6	-0.14	0.23	-10000	0	-0.61	35	35
PRKACG	0.002	0.005	-10000	0	-10000	0	0
IL5	-0.21	0.22	-10000	0	-0.69	29	29
IL2	-0.24	0.24	-10000	0	-0.6	62	62
CDK5	0.015	0.005	-10000	0	-10000	0	0
PRKACB	0.006	0.056	-10000	0	-0.4	5	5
HSP90AA1	0.012	0.026	-10000	0	-0.43	1	1
IL8	-0.17	0.28	-10000	0	-0.66	49	49
CDK5R1/CDK5	0.016	0.051	-10000	0	-0.3	7	7
NF kappa B1 p50/RelA/PKAc	0.001	0.094	-10000	0	-0.29	10	10
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.24	0.2	0.45	108	-10000	0	108
SMARCA4	0.014	0.011	-10000	0	-10000	0	0
chromatin remodeling	0.16	0.14	0.34	65	-0.32	1	66
NF kappa B1 p50/RelA/Cbp	0.058	0.14	0.31	31	-0.29	9	40
JUN (dimer)	-0.18	0.17	-10000	0	-0.38	94	94
YWHAH	0.014	0	-10000	0	-10000	0	0
VIPR1	-0.12	0.2	-10000	0	-0.44	53	53
NR3C1	0.16	0.16	0.35	85	-0.33	4	89
NR4A1	-0.038	0.14	-10000	0	-0.44	28	28
TIF2/SUV420H1	0.009	0.057	-10000	0	-0.29	10	10
MAPKKK cascade	0.083	0.16	0.5	25	-10000	0	25
cortisol/GR alpha (dimer)/Src-1	0.25	0.22	0.48	107	-10000	0	107
PBX1	-0.011	0.091	-10000	0	-0.33	20	20
POU1F1	0.002	0.018	-10000	0	-10000	0	0
SELE	-0.19	0.31	-10000	0	-0.75	53	53
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.16	0.14	0.34	64	-0.32	1	65
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.24	0.2	0.45	108	-10000	0	108
mol:cortisol	0.15	0.16	0.32	103	-10000	0	103
MMP1	-0.26	0.39	-10000	0	-0.81	72	72

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	-0.032	0.12	-10000	0	-0.42	20	20
NFATC2	-0.11	0.28	-10000	0	-0.65	45	45
NFATC3	-0.01	0.067	-10000	0	-0.22	10	10
CD40LG	-0.24	0.39	-10000	0	-0.85	63	63
ITCH	-0.027	0.091	-10000	0	-10000	0	0
CBLB	-0.027	0.091	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.26	0.48	-10000	0	-1	70	70
JUNB	0.012	0.019	-10000	0	-0.31	1	1
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.044	0.11	-10000	0	-0.25	41	41
T cell anergy	-0.08	0.15	-10000	0	-0.38	41	41
TLE4	-0.081	0.24	-10000	0	-0.58	38	38
Jun/NFAT1-c-4/p21SNFT	-0.17	0.36	-10000	0	-0.81	52	52
AP-1/NFAT1-c-4	-0.23	0.44	-10000	0	-0.91	63	63
IKZF1	-0.099	0.27	-10000	0	-0.65	43	43
T-helper 2 cell differentiation	-0.15	0.33	-10000	0	-0.78	52	52
AP-1/NFAT1	-0.074	0.2	-10000	0	-0.45	44	44
CALM1	-0.021	0.064	-10000	0	-10000	0	0
EGR2	-0.12	0.31	-10000	0	-0.78	33	33
EGR3	-0.16	0.39	-10000	0	-1.1	31	31
NFAT1/FOXP3	-0.11	0.26	-10000	0	-0.56	51	51
EGR1	-0.001	0.069	-10000	0	-0.33	12	12
JUN	0.001	0.021	-10000	0	-10000	0	0
EGR4	-0.017	0.091	-10000	0	-0.31	25	25
mol:Ca2+	-0.036	0.065	-10000	0	-0.16	41	41
GBP3	-0.096	0.27	-10000	0	-0.66	42	42
FOSL1	-0.048	0.14	-10000	0	-0.38	44	44
NFAT1-c-4/MAF/IRF4	-0.16	0.34	-10000	0	-0.79	48	48
DGKA	-0.07	0.23	-10000	0	-0.61	29	29
CREM	0.012	0.019	-10000	0	-0.31	1	1
NFAT1-c-4/PPARG	-0.15	0.35	-10000	0	-0.84	45	45
CTLA4	-0.13	0.28	-10000	0	-0.62	59	59
NFAT1-c-4 (dimer)/EGR1	-0.15	0.35	-10000	0	-0.84	45	45
NFAT1-c-4 (dimer)/EGR4	-0.16	0.35	-10000	0	-0.84	46	46
FOS	-0.007	0.055	-10000	0	-0.33	7	7
IFNG	-0.3	0.5	-10000	0	-1	76	76
T cell activation	-0.08	0.22	-10000	0	-0.65	18	18
MAF	0.014	0	-10000	0	-10000	0	0
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.1	0.27	0.78	27	-10000	0	27
TNF	-0.16	0.34	-10000	0	-0.82	48	48
FASLG	-0.33	0.62	-10000	0	-1.4	65	65
TBX21	-0.078	0.17	-10000	0	-0.4	55	55
BATF3	0.003	0.064	-10000	0	-0.37	8	8
PRKCQ	-0.071	0.17	-10000	0	-0.42	52	52
PTPN1	-0.065	0.21	-10000	0	-0.56	30	30
NFAT1-c-4/ICER1	-0.14	0.34	-10000	0	-0.84	43	43
GATA3	-0.061	0.16	-10000	0	-0.4	51	51
T-helper 1 cell differentiation	-0.29	0.48	-10000	0	-1	77	77
IL2RA	-0.22	0.43	-10000	0	-0.93	62	62
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.064	0.21	-10000	0	-0.54	32	32
E2F1	0.015	0.038	-10000	0	-0.43	2	2
PPARG	0.002	0.069	-10000	0	-0.4	8	8
SLC3A2	-0.064	0.21	-10000	0	-0.6	25	25
IRF4	-0.045	0.15	-10000	0	-0.43	37	37
PTGS2	-0.23	0.39	-10000	0	-0.82	67	67
CSF2	-0.22	0.37	-10000	0	-0.8	62	62
JunB/Fra1/NFAT1-c-4	-0.16	0.34	-10000	0	-0.83	45	45
IL4	-0.16	0.35	-10000	0	-0.83	51	51
IL5	-0.22	0.36	-10000	0	-0.8	61	61
IL2	-0.081	0.22	-10000	0	-0.67	17	17
IL3	-0.044	0.054	-10000	0	-10000	0	0
RNF128	-0.11	0.2	-10000	0	-0.47	48	48
NFATC1	-0.1	0.27	-10000	0	-0.78	27	27
CDK4	0.082	0.19	0.56	15	-10000	0	15
PTPRK	-0.07	0.22	-10000	0	-0.59	31	31
IL8	-0.23	0.38	-10000	0	-0.81	68	68
POU2F1	0.014	0.001	-10000	0	-10000	0	0

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.13	0.34	-10000	0	-0.78	54	54
NCK1/PAK1/Dok-R	-0.088	0.15	-10000	0	-0.39	52	52
NCK1/Dok-R	-0.14	0.38	-10000	0	-0.95	50	50
PIK3CA	0.007	0.052	-10000	0	-0.43	4	4
mol:beta2-estradiol	0.042	0.089	0.23	50	-10000	0	50
RELA	0.014	0	-10000	0	-10000	0	0
SHC1	0.013	0.002	-10000	0	-10000	0	0
Rac/GDP	0.01	0	-10000	0	-10000	0	0
F2	0.041	0.098	0.23	49	-0.32	3	52
TNIP2	0.014	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.13	0.36	-10000	0	-0.88	50	50
FN1	-0.012	0.1	-10000	0	-0.42	17	17
PLD2	-0.15	0.39	-10000	0	-0.96	50	50
PTPN11	0.014	0	-10000	0	-10000	0	0
GRB14	-0.07	0.16	-10000	0	-0.37	60	60
ELK1	-0.13	0.35	-10000	0	-0.87	50	50
GRB7	-0.027	0.1	-10000	0	-0.31	33	33
PAK1	0.01	0.037	-10000	0	-0.35	3	3
Tie2/Ang1/alpha5/beta1 Integrin	-0.15	0.38	-10000	0	-0.93	51	51
CDKN1A	-0.085	0.26	-10000	0	-0.59	42	42
ITGA5	0.003	0.062	-10000	0	-0.35	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.15	0.39	-10000	0	-0.95	50	50
CRK	0.014	0	-10000	0	-10000	0	0
mol:NO	-0.089	0.26	-10000	0	-0.58	58	58
PLG	-0.16	0.39	-10000	0	-0.97	50	50
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.12	0.32	-10000	0	-0.76	52	52
GRB2	0.014	0	-10000	0	-10000	0	0
PIK3R1	0.01	0.037	-10000	0	-0.43	2	2
ANGPT2	-0.096	0.26	-10000	0	-1	13	13
BMX	-0.19	0.39	-10000	0	-0.99	50	50
ANGPT1	-0.21	0.45	-10000	0	-1.2	51	51
tube development	-0.089	0.26	-10000	0	-0.56	56	56
ANGPT4	0.001	0.038	-10000	0	-0.31	4	4
response to hypoxia	-0.012	0.026	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.19	0.4	-10000	0	-1	51	51
alpha5/beta1 Integrin	0.011	0.051	-10000	0	-0.26	9	9
FGF2	-0.076	0.18	-10000	0	-0.42	59	59
STAT5A (dimer)	-0.1	0.3	-10000	0	-0.63	59	59
mol:L-citrulline	-0.089	0.26	-10000	0	-0.58	58	58
AGTR1	-0.04	0.13	-10000	0	-0.37	38	38
MAPK14	-0.14	0.37	-10000	0	-0.92	50	50
Tie2/SHP2	-0.023	0.14	-10000	0	-1.1	2	2
TEK	-0.031	0.15	-10000	0	-1.2	2	2
RPS6KB1	-0.12	0.32	-10000	0	-0.75	52	52
Angiotensin II/AT1	-0.027	0.093	-10000	0	-0.26	38	38
Tie2/Ang1/GRB2	-0.16	0.4	-10000	0	-0.99	50	50
MAPK3	-0.14	0.36	-10000	0	-0.89	50	50
MAPK1	-0.14	0.36	-10000	0	-0.89	50	50
Tie2/Ang1/GRB7	-0.17	0.4	-10000	0	-1	50	50
NFKB1	0.014	0	-10000	0	-10000	0	0
MAPK8	-0.16	0.39	-10000	0	-0.97	50	50
PI3K	-0.14	0.37	-10000	0	-0.88	52	52
FES	-0.16	0.38	-10000	0	-0.92	53	53
Crk/Dok-R	-0.14	0.38	-10000	0	-0.95	50	50
Tie2/Ang1/ABIN2	-0.16	0.4	-10000	0	-0.99	50	50
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.11	0.3	-10000	0	-0.69	56	56
STAT5A	0.012	0.026	-10000	0	-0.43	1	1
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.12	0.32	-10000	0	-0.75	52	52
Tie2/Ang2	-0.13	0.34	-10000	0	-0.74	56	56
Tie2/Ang1	-0.17	0.41	-10000	0	-1	50	50
FOXO1	-0.11	0.31	-10000	0	-0.71	56	56
ELF1	0.015	0.031	-10000	0	-0.46	1	1
ELF2	-0.15	0.38	-10000	0	-0.95	50	50
mol:Choline	-0.15	0.37	-10000	0	-0.93	50	50
cell migration	-0.052	0.086	-10000	0	-0.22	53	53
FYN	-0.1	0.29	-10000	0	-0.63	56	56
DOK2	-0.001	0.078	-10000	0	-0.43	9	9
negative regulation of cell cycle	-0.075	0.24	-10000	0	-0.53	43	43
ETS1	-0.029	0.092	-10000	0	-0.22	44	44
PXN	-0.09	0.27	-10000	0	-0.63	52	52
ITGB1	0.011	0.032	-10000	0	-0.37	2	2
NOS3	-0.1	0.29	-10000	0	-0.66	55	55
RAC1	0.014	0	-10000	0	-10000	0	0
TNF	-0.063	0.15	-10000	0	-0.29	68	68
MAPKKK cascade	-0.15	0.37	-10000	0	-0.93	50	50
RASA1	0.009	0.045	-10000	0	-0.43	3	3
Tie2/Ang1/Shc	-0.16	0.4	-10000	0	-0.99	50	50
NCK1	0.014	0	-10000	0	-10000	0	0
vasculogenesis	-0.077	0.24	-10000	0	-0.52	58	58
mol:Phosphatidic acid	-0.15	0.37	-10000	0	-0.93	50	50
mol:Angiotensin II	-0.001	0.006	-10000	0	-10000	0	0
mol:NADP	-0.089	0.26	-10000	0	-0.58	58	58
Rac1/GTP	-0.15	0.28	-10000	0	-0.71	52	52
MMP2	-0.17	0.4	-10000	0	-0.99	50	50

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.091	0.16	-10000	0	-0.39	49	49
IKBKB	-0.038	0.086	-10000	0	-0.23	29	29
AKT1	-0.073	0.1	0.19	2	-0.22	64	66
IKBKG	-0.039	0.091	-10000	0	-0.25	29	29
CALM1	-0.08	0.18	-10000	0	-0.53	31	31
PIK3CA	0.007	0.052	-10000	0	-0.43	4	4
MAP3K1	-0.15	0.24	-10000	0	-0.54	61	61
MAP3K7	0.009	0.045	-10000	0	-0.43	3	3
mol:Ca2+	-0.091	0.2	-10000	0	-0.56	32	32
DOK1	0.011	0.032	-10000	0	-0.37	2	2
AP-1	-0.04	0.091	-10000	0	-0.25	31	31
LYN	0.012	0.026	-10000	0	-0.43	1	1
BLNK	-0.036	0.14	-10000	0	-0.41	33	33
SHC1	0.014	0	-10000	0	-10000	0	0
BCR complex	-0.13	0.18	-10000	0	-0.32	124	124
CD22	-0.15	0.23	-10000	0	-0.5	66	66
CAMK2G	-0.07	0.17	-10000	0	-0.48	31	31
CSNK2A1	0.014	0	-10000	0	-10000	0	0
INPP5D	-0.009	0.095	-10000	0	-0.39	16	16
SHC/GRB2/SOS1	-0.11	0.16	-10000	0	-0.39	49	49
GO:0007205	-0.093	0.2	-10000	0	-0.57	32	32
SYK	-0.011	0.099	-10000	0	-0.4	17	17
ELK1	-0.082	0.19	-10000	0	-0.54	31	31
NFATC1	-0.13	0.19	-10000	0	-0.42	61	61
B-cell antigen/BCR complex	-0.13	0.18	-10000	0	-0.32	124	124
PAG1/CSK	0.009	0.058	-10000	0	-0.3	10	10
NFKBIB	-0.004	0.03	-10000	0	-0.077	8	8
HRAS	-0.08	0.18	-10000	0	-0.48	34	34
NFKBIA	-0.004	0.029	-10000	0	-0.078	5	5
NF-kappa-B/RelA/I kappa B beta	0.002	0.024	-10000	0	-10000	0	0
RasGAP/Csk	-0.084	0.15	-10000	0	-0.33	46	46
mol:GDP	-0.087	0.19	-10000	0	-0.56	31	31
PTEN	0.002	0.069	-10000	0	-0.43	7	7
CD79B	-0.056	0.15	-10000	0	-0.36	52	52
NF-kappa-B/RelA/I kappa B alpha	0.002	0.024	-10000	0	-10000	0	0
GRB2	0.014	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.16	0.22	-10000	0	-0.51	64	64
PIK3R1	0.01	0.037	-10000	0	-0.43	2	2
mol:IP3	-0.094	0.2	-10000	0	-0.58	32	32
CSK	0.014	0	-10000	0	-10000	0	0
FOS	-0.074	0.17	-10000	0	-0.49	32	32
CHUK	-0.04	0.092	-10000	0	-0.26	27	27
IBTK	0.003	0.069	-10000	0	-0.43	7	7
CARD11/BCL10/MALT1/TAK1	-0.087	0.19	-10000	0	-0.45	45	45
PTPN6	-0.15	0.24	-10000	0	-0.5	65	65
RELA	0.013	0	-10000	0	-10000	0	0
BCL2A1	-0.001	0.027	-10000	0	-0.083	7	7
VAV2	-0.19	0.26	-10000	0	-0.56	68	68
ubiquitin-dependent protein catabolic process	0	0.029	-10000	0	-0.074	4	4
BTK	-0.027	0.19	-10000	0	-0.98	10	10
CD19	-0.18	0.24	-10000	0	-0.49	80	80
MAP4K1	-0.024	0.12	-10000	0	-0.4	25	25
CD72	-0.021	0.11	-10000	0	-0.36	26	26
PAG1	-0.002	0.082	-10000	0	-0.43	10	10
MAPK14	-0.12	0.2	-10000	0	-0.45	60	60
SH3BP5	0.01	0.037	-10000	0	-0.35	3	3
PIK3AP1	-0.099	0.24	-10000	0	-0.62	36	36
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.13	0.3	-10000	0	-0.52	70	70
RAF1	-0.07	0.17	-10000	0	-0.47	31	31
RasGAP/p62DOK/SHIP	-0.088	0.16	-10000	0	-0.37	48	48
CD79A	-0.14	0.19	-10000	0	-0.37	111	111
re-entry into mitotic cell cycle	-0.041	0.092	-10000	0	-0.25	31	31
RASA1	0.009	0.045	-10000	0	-0.43	3	3
MAPK3	-0.048	0.14	-10000	0	-0.4	28	28
MAPK1	-0.048	0.14	-10000	0	-0.4	28	28
CD72/SHP1	-0.15	0.24	-10000	0	-0.49	69	69
NFKB1	0.013	0	-10000	0	-10000	0	0
MAPK8	-0.12	0.2	-10000	0	-0.45	61	61
actin cytoskeleton organization	-0.16	0.22	-10000	0	-0.48	67	67
NF-kappa-B/RelA	0.009	0.046	-10000	0	-10000	0	0
Calcineurin	-0.056	0.15	-10000	0	-0.46	28	28
PI3K	-0.17	0.19	-10000	0	-0.42	83	83
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.1	0.23	-10000	0	-0.63	34	34
SOS1	0.014	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.17	0.34	-10000	0	-0.9	43	43
DAPP1	-0.19	0.39	-10000	0	-1.1	42	42
cytokine secretion	-0.12	0.18	-10000	0	-0.39	61	61
mol:DAG	-0.094	0.2	-10000	0	-0.58	32	32
PLCG2	-0.001	0.078	-10000	0	-0.4	10	10
MAP2K1	-0.059	0.15	-10000	0	-0.46	28	28
B-cell antigen/BCR complex/FcgammaRIIB	-0.11	0.17	-10000	0	-0.32	93	93
mol:PI-3-4-5-P3	-0.12	0.13	0.2	3	-0.3	80	83
ETS1	-0.059	0.15	-10000	0	-0.46	28	28
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.11	0.2	-10000	0	-0.32	98	98
B-cell antigen/BCR complex/LYN	-0.14	0.22	-10000	0	-0.6	39	39
MALT1	0.01	0.037	-10000	0	-0.43	2	2
TRAF6	0.014	0	-10000	0	-10000	0	0
RAC1	-0.17	0.23	-10000	0	-0.51	67	67
B-cell antigen/BCR complex/LYN/SYK	-0.15	0.24	-10000	0	-0.51	67	67
CARD11	-0.11	0.23	-10000	0	-0.49	54	54
FCGR2B	-0.008	0.088	-10000	0	-0.35	17	17
PPP3CA	0.01	0.037	-10000	0	-0.43	2	2
BCL10	0.012	0.019	-10000	0	-0.31	1	1
IKK complex	-0.011	0.037	-10000	0	-0.091	18	18
PTPRC	-0.056	0.15	-10000	0	-0.38	49	49
PDPK1	-0.073	0.098	0.17	2	-0.21	73	75
PPP3CB	0.014	0	-10000	0	-10000	0	0
PPP3CC	0.014	0	-10000	0	-10000	0	0
POU2F2	0.002	0.027	-10000	0	-0.093	8	8

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.011	0.052	-10000	0	-0.3	8	8
Necdin/E2F1	-0.011	0.095	-10000	0	-0.3	28	28
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.032	0.12	-10000	0	-0.23	58	58
NGF (dimer)/p75(NTR)/BEX1	-0.094	0.14	-10000	0	-0.24	129	129
NT-4/5 (dimer)/p75(NTR)	-0.054	0.12	-10000	0	-0.25	74	74
IKBKB	0.014	0	-10000	0	-10000	0	0
AKT1	-0.031	0.1	-10000	0	-0.21	52	52
IKBKG	0.014	0	-10000	0	-10000	0	0
BDNF	-0.099	0.18	-10000	0	-0.37	82	82
MGDIs/NGR/p75(NTR)/LINGO1	-0.085	0.17	-10000	0	-0.33	74	74
FURIN	0.014	0	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.096	0.14	-10000	0	-0.28	82	82
LINGO1	-0.039	0.14	-10000	0	-0.42	34	34
Sortilin/TRAF6/NRIF	-0.006	0.029	-10000	0	-10000	0	0
proBDNF (dimer)	-0.099	0.18	-10000	0	-0.37	82	82
NTRK1	-0.014	0.099	-10000	0	-0.37	20	20
RTN4R	-0.044	0.14	-10000	0	-0.4	39	39
neuron apoptosis	-0.067	0.13	-10000	0	-0.37	16	16
IRAK1	0.014	0	-10000	0	-10000	0	0
SHC1	-0.045	0.11	-10000	0	-0.26	48	48
ARHGDIA	0.012	0.026	-10000	0	-0.43	1	1
RhoA/GTP	0.01	0	-10000	0	-10000	0	0
Gamma Secretase	0.039	0.02	-10000	0	-0.19	2	2
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.038	0.12	-10000	0	-0.24	55	55
MAGEH1	0.009	0.045	-10000	0	-0.43	3	3
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.057	0.14	-10000	0	-0.27	70	70
Mammalian IAPs/DIABLO	-0.008	0.1	-10000	0	-0.26	31	31
proNGF (dimer)	-0.02	0.11	-10000	0	-0.38	24	24
MAGED1	0.012	0.026	-10000	0	-0.43	1	1
APP	-0.013	0.1	-10000	0	-0.43	17	17
NT-4/5 (dimer)	-0.008	0.066	-10000	0	-0.31	13	13
ZNF274	0.014	0	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.03	0.098	-10000	0	-0.21	49	49
NGF	-0.02	0.11	-10000	0	-0.38	24	24
cell cycle arrest	-0.027	0.11	0.14	12	-0.21	51	63
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.017	0.087	-10000	0	-0.2	42	42
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.035	0.1	-10000	0	-0.22	53	53
NCSTN	0.014	0	-10000	0	-10000	0	0
mol:GTP	-0.047	0.12	-10000	0	-0.26	51	51
PSENEN	0.014	0	-10000	0	-10000	0	0
mol:ceramide	-0.042	0.11	-10000	0	-0.24	54	54
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.013	0.086	-10000	0	-0.33	5	5
p75(NTR)/beta APP	-0.058	0.13	-10000	0	-0.26	77	77
BEX1	-0.077	0.15	-10000	0	-0.34	72	72
mol:GDP	-0.054	0.11	-10000	0	-0.22	80	80
NGF (dimer)	-0.035	0.1	-10000	0	-0.25	33	33
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.07	0.16	-10000	0	-0.3	74	74
PIK3R1	0.01	0.037	-10000	0	-0.43	2	2
RAC1/GTP	-0.035	0.097	-10000	0	-0.22	48	48
MYD88	0.012	0.026	-10000	0	-0.43	1	1
CHUK	0.012	0.026	-10000	0	-0.43	1	1
NGF (dimer)/p75(NTR)/PKA	-0.047	0.12	-10000	0	-0.26	51	51
RHOB	0.014	0	-10000	0	-10000	0	0
RHOA	0.014	0	-10000	0	-10000	0	0
MAGE-G1/E2F1	0.018	0.027	-10000	0	-0.3	2	2
NT3 (dimer)	-0.024	0.1	-10000	0	-0.31	31	31
TP53	-0.066	0.12	-10000	0	-0.32	20	20
PRDM4	-0.041	0.11	-10000	0	-0.24	53	53
BDNF (dimer)	-0.14	0.14	-10000	0	-0.28	112	112
PIK3CA	0.007	0.052	-10000	0	-0.43	4	4
SORT1	0.001	0.074	-10000	0	-0.43	8	8
activation of caspase activity	-0.034	0.11	-10000	0	-0.23	58	58
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.036	0.12	-10000	0	-0.24	53	53
RHOC	0.014	0	-10000	0	-10000	0	0
XIAP	0.01	0.037	-10000	0	-0.43	2	2
MAPK10	-0.077	0.14	-10000	0	-0.3	56	56
DIABLO	0.014	0	-10000	0	-10000	0	0
SMPD2	-0.042	0.12	-10000	0	-0.24	54	54
APH1B	0.01	0.037	-10000	0	-0.43	2	2
APH1A	0.014	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.05	0.13	-10000	0	-0.27	53	53
PSEN1	0.014	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.016	0.037	-10000	0	-0.3	4	4
NT3 (dimer)/p75(NTR)	-0.064	0.13	-10000	0	-0.26	85	85
MAPK8	-0.061	0.12	-10000	0	-0.3	32	32
MAPK9	-0.059	0.12	-10000	0	-0.28	46	46
APAF1	0.007	0.052	-10000	0	-0.43	4	4
NTF3	-0.024	0.1	-10000	0	-0.31	31	31
NTF4	-0.008	0.066	-10000	0	-0.31	13	13
NDN	-0.027	0.13	-10000	0	-0.43	26	26
RAC1/GDP	0.01	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.022	0.093	-10000	0	-0.27	9	9
p75 CTF/Sortilin/TRAF6/NRIF	0.028	0.041	-10000	0	-0.21	8	8
RhoA-B-C/GTP	-0.047	0.12	-10000	0	-0.26	51	51
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.067	0.12	-10000	0	-0.23	82	82
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.079	0.13	-10000	0	-0.25	82	82
PRKACB	0.006	0.056	-10000	0	-0.4	5	5
proBDNF (dimer)/p75 ECD	-0.059	0.13	-10000	0	-0.25	82	82
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.052	0.15	-10000	0	-0.38	47	47
BIRC2	0.003	0.066	-10000	0	-0.41	7	7
neuron projection morphogenesis	-0.047	0.13	0.16	12	-0.27	47	59
BAD	-0.064	0.13	-10000	0	-0.28	49	49
RIPK2	0.014	0	-10000	0	-10000	0	0
NGFR	-0.071	0.16	-10000	0	-0.36	64	64
CYCS	-0.033	0.11	-10000	0	-0.22	54	54
ADAM17	0.014	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.029	0.11	-10000	0	-0.23	48	48
BCL2L11	-0.064	0.13	-10000	0	-0.28	49	49
BDNF (dimer)/p75(NTR)	-0.12	0.16	-10000	0	-0.27	132	132
PI3K	-0.034	0.11	-10000	0	-0.23	52	52
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.036	0.12	-10000	0	-0.24	53	53
NDNL2	0.014	0	-10000	0	-10000	0	0
YWHAE	0.014	0	-10000	0	-10000	0	0
PRKCI	0.007	0.052	-10000	0	-0.43	4	4
NGF (dimer)/p75(NTR)	-0.062	0.14	-10000	0	-0.27	80	80
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.037	0.12	-10000	0	-0.24	54	54
TRAF6	0.014	0	-10000	0	-10000	0	0
RAC1	0.014	0	-10000	0	-10000	0	0
PRKCZ	0.003	0.069	-10000	0	-0.43	7	7
PLG	-0.001	0.026	-10000	0	-0.31	2	2
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.088	0.14	-10000	0	-0.25	97	97
SQSTM1	0.014	0	-10000	0	-10000	0	0
NGFRAP1	0.003	0.069	-10000	0	-0.43	7	7
CASP3	-0.058	0.12	-10000	0	-0.27	49	49
E2F1	0.01	0.037	-10000	0	-0.43	2	2
CASP9	0.014	0	-10000	0	-10000	0	0
IKK complex	-0.041	0.078	-10000	0	-0.25	21	21
NGF (dimer)/TRKA	-0.023	0.1	-10000	0	-0.26	43	43
MMP7	-0.067	0.15	-10000	0	-0.35	62	62
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.027	0.11	-10000	0	-0.22	53	53
MMP3	-0.099	0.17	-10000	0	-0.35	85	85
APAF-1/Caspase 9	-0.065	0.1	-10000	0	-0.32	26	26

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	-0.041	0.1	-10000	0	-0.2	79	79
epithelial cell differentiation	-0.041	0.1	-10000	0	-0.2	79	79
CYFIP2	-0.013	0.1	-10000	0	-0.41	18	18
ENAH	-0.014	0.083	-10000	0	-0.24	8	8
EGFR	-0.028	0.12	-10000	0	-0.34	33	33
EPHA2	-0.006	0.089	-10000	0	-0.41	13	13
MYO6	-0.044	0.1	-10000	0	-0.19	88	88
CTNNB1	0.014	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.011	0.063	-10000	0	-0.24	15	15
AQP5	-0.047	0.11	-10000	0	-0.47	6	6
CTNND1	0.014	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.036	0.095	-10000	0	-0.18	79	79
regulation of calcium-dependent cell-cell adhesion	-0.047	0.11	-10000	0	-0.2	84	84
EGF	-0.097	0.18	-10000	0	-0.4	76	76
NCKAP1	0.014	0	-10000	0	-10000	0	0
AQP3	-0.053	0.14	-10000	0	-0.49	17	17
cortical microtubule organization	-0.041	0.1	-10000	0	-0.2	79	79
GO:0000145	-0.035	0.09	-10000	0	-0.17	79	79
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.04	0.1	-10000	0	-0.2	79	79
MLLT4	0.006	0.056	-10000	0	-0.4	5	5
ARF6/GDP	-0.051	0.071	-10000	0	-0.28	4	4
ARF6	0.014	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.024	0.05	-10000	0	-0.21	11	11
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.028	0.092	-10000	0	-0.22	2	2
PVRL2	0.014	0	-10000	0	-10000	0	0
ZYX	-0.037	0.099	-10000	0	-0.19	79	79
ARF6/GTP	0.028	0.046	-10000	0	-0.19	11	11
CDH1	-0.12	0.2	-10000	0	-0.41	92	92
EGFR/EGFR/EGF/EGF	-0.11	0.13	-10000	0	-0.37	40	40
RhoA/GDP	-0.036	0.095	-10000	0	-0.18	79	79
actin cytoskeleton organization	-0.038	0.099	-10000	0	-0.33	2	2
IGF-1R heterotetramer	0.009	0.042	-10000	0	-0.39	3	3
GIT1	0.014	0	-10000	0	-10000	0	0
IGF1R	0.009	0.042	-10000	0	-0.39	3	3
IGF1	-0.02	0.11	-10000	0	-0.4	23	23
DIAPH1	-0.026	0.13	-10000	0	-0.58	15	15
Wnt receptor signaling pathway	0.041	0.1	0.2	79	-10000	0	79
RHOA	0.014	0	-10000	0	-10000	0	0
RhoA/GTP	-0.051	0.071	-10000	0	-0.28	4	4
CTNNA1	0.014	0	-10000	0	-10000	0	0
VCL	-0.039	0.1	-10000	0	-0.34	2	2
EFNA1	0.014	0	-10000	0	-10000	0	0
LPP	-0.033	0.093	-10000	0	-10000	0	0
Ephrin A1/EPHA2	-0.061	0.085	-10000	0	-0.32	4	4
SEC6/SEC8	-0.05	0.071	-10000	0	-0.34	1	1
MGAT3	-0.048	0.11	-10000	0	-0.2	84	84
HGF/MET	-0.094	0.12	-10000	0	-0.34	32	32
HGF	-0.025	0.11	-10000	0	-0.36	29	29
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.041	0.1	-10000	0	-0.2	79	79
actin cable formation	-0.003	0.082	-10000	0	-0.23	5	5
KIAA1543	-0.077	0.12	-10000	0	-0.32	26	26
KIFC3	-0.037	0.097	-10000	0	-0.18	80	80
NCK1	0.014	0	-10000	0	-10000	0	0
EXOC3	0.012	0.019	-10000	0	-0.31	1	1
ACTN1	-0.039	0.098	-10000	0	-0.18	83	83
NCK1/GIT1	0.02	0	-10000	0	-10000	0	0
mol:GDP	-0.041	0.1	-10000	0	-0.2	79	79
EXOC4	0.014	0	-10000	0	-10000	0	0
STX4	-0.036	0.096	-10000	0	-0.18	79	79
PIP5K1C	-0.036	0.096	-10000	0	-0.18	79	79
LIMA1	0.014	0	-10000	0	-10000	0	0
ABI1	0.014	0	-10000	0	-10000	0	0
ROCK1	-0.019	0.087	-10000	0	-0.26	5	5
adherens junction assembly	-0.059	0.12	-10000	0	-0.3	23	23
IGF-1R heterotetramer/IGF1	-0.068	0.092	-10000	0	-0.19	92	92
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.015	0.04	-10000	0	-0.28	5	5
MET	-0.051	0.15	-10000	0	-0.4	44	44
PLEKHA7	-0.047	0.11	-10000	0	-0.2	87	87
mol:GTP	0.023	0.049	-10000	0	-0.21	11	11
establishment of epithelial cell apical/basal polarity	-0.016	0.089	-10000	0	-0.32	1	1
cortical actin cytoskeleton stabilization	-0.041	0.1	-10000	0	-0.2	79	79
regulation of cell-cell adhesion	-0.038	0.099	-10000	0	-0.33	2	2
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.041	0.1	-10000	0	-0.2	79	79

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	-0.089	0.19	-9999	-0.39	79	79
KLHL20	-0.015	0.082	-9999	-0.2	14	14
CYFIP2	-0.013	0.1	-9999	-0.41	18	18
Rac1/GDP	-0.031	0.12	-9999	-0.22	75	75
ENAH	-0.093	0.19	-9999	-0.4	79	79
AP1M1	0.014	0	-9999	-10000	0	0
RAP1B	0.012	0.019	-9999	-0.31	1	1
RAP1A	0.014	0	-9999	-10000	0	0
CTNNB1	0.014	0	-9999	-10000	0	0
CDC42/GTP	-0.043	0.064	-9999	-0.28	2	2
ABI1/Sra1/Nap1	-0.033	0.046	-9999	-0.15	19	19
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.058	0.13	-9999	-0.23	91	91
RAPGEF1	-0.068	0.17	-9999	-0.34	79	79
CTNND1	0.014	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.097	0.2	-9999	-0.41	79	79
CRK	-0.079	0.18	-9999	-0.37	79	79
E-cadherin/gamma catenin/alpha catenin	-0.065	0.13	-9999	-0.23	101	101
alphaE/beta7 Integrin	-0.002	0.08	-9999	-0.29	20	20
IQGAP1	0.014	0	-9999	-10000	0	0
NCKAP1	0.014	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.022	0.032	-9999	-0.22	4	4
DLG1	-0.089	0.19	-9999	-0.39	79	79
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.033	0.049	-9999	-0.22	3	3
MLLT4	0.006	0.056	-9999	-0.4	5	5
ARF6/GTP/NME1/Tiam1	0.011	0.059	-9999	-0.22	17	17
PI3K	-0.041	0.062	-9999	-0.29	3	3
ARF6	0.014	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.089	0.15	-9999	-0.28	101	101
TIAM1	-0.014	0.11	-9999	-0.42	18	18
E-cadherin(dimer)/Ca2+	-0.04	0.1	-9999	-0.2	79	79
AKT1	-0.024	0.036	-9999	-0.16	3	3
PIK3R1	0.01	0.037	-9999	-0.43	2	2
CDH1	-0.12	0.2	-9999	-0.41	92	92
RhoA/GDP	-0.032	0.12	-9999	-0.22	75	75
actin cytoskeleton organization	-0.01	0.063	-9999	-0.15	14	14
CDC42/GDP	-0.032	0.12	-9999	-0.22	75	75
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.052	0.11	-9999	-0.21	80	80
ITGB7	-0.017	0.11	-9999	-0.42	20	20
RAC1	0.014	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.042	0.11	-9999	-0.21	79	79
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.047	0.1	-9999	-0.2	79	79
mol:GDP	-0.045	0.13	-9999	-0.26	79	79
CDC42/GTP/IQGAP1	0.018	0	-9999	-10000	0	0
JUP	-0.002	0.072	-9999	-0.32	13	13
p120 catenin/RhoA/GDP	-0.032	0.12	-9999	-0.22	75	75
RAC1/GTP/IQGAP1	0.018	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0.02	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	-0.004	0.047	-9999	-0.15	7	7
NME1	0.014	0	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	-0.093	0.19	-9999	-0.39	79	79
regulation of cell-cell adhesion	-0.039	0.057	-9999	-0.24	2	2
WASF2	-0.017	0.025	-9999	-0.11	2	2
Rap1/GTP	-0.049	0.074	-9999	-0.32	2	2
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.056	0.13	-9999	-0.22	91	91
CCND1	-0.006	0.057	-9999	-0.19	7	7
VAV2	-0.089	0.2	-9999	-0.39	84	84
RAP1/GDP	-0.025	0.1	-9999	-0.3	3	3
adherens junction assembly	-0.09	0.18	-9999	-0.38	79	79
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	-0.049	0.12	-9999	-0.38	12	12
E-cadherin/beta catenin	-0.091	0.14	-9999	-0.31	79	79
mol:GTP	0	0	-9999	-10000	0	0
SRC	-0.089	0.19	-9999	-0.39	79	79
PIK3CA	0.007	0.052	-9999	-0.43	4	4
Rac1/GTP	-0.066	0.098	-9999	-0.33	14	14
E-cadherin/beta catenin/alpha catenin	-0.056	0.12	-9999	-0.24	79	79
ITGAE	0.014	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.099	0.2	-9999	-0.42	79	79

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	-0.008	0.074	-10000	0	-0.28	7	7
adherens junction organization	-0.042	0.12	-10000	0	-0.22	79	79
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.018	0.09	-10000	0	-0.24	18	18
FMN1	-0.05	0.13	-10000	0	-0.23	79	79
mol:IP3	-0.013	0.072	-10000	0	-0.25	8	8
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.047	0.12	-10000	0	-0.22	79	79
CTNNB1	0.016	0.004	-10000	0	-10000	0	0
AKT1	-0.015	0.082	-10000	0	-0.31	5	5
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.077	0.17	-10000	0	-0.35	79	79
CTNND1	0.013	0.002	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.038	0.11	-10000	0	-0.2	79	79
VASP	-0.039	0.11	-10000	0	-0.21	79	79
ZYX	-0.04	0.11	-10000	0	-0.21	79	79
JUB	-0.04	0.11	-10000	0	-0.21	79	79
EGFR(dimer)	-0.056	0.13	-10000	0	-0.24	81	81
E-cadherin/beta catenin-gamma catenin	-0.061	0.12	-10000	0	-0.22	101	101
mol:PI-3-4-5-P3	-0.021	0.086	-10000	0	-0.27	8	8
PIK3CA	0.007	0.053	-10000	0	-0.43	4	4
PI3K	-0.021	0.088	-10000	0	-0.28	8	8
FYN	-0.004	0.066	-10000	0	-0.26	5	5
mol:Ca2+	-0.013	0.071	-10000	0	-0.24	8	8
JUP	0	0.072	-10000	0	-0.32	13	13
PIK3R1	0.01	0.038	-10000	0	-0.44	2	2
mol:DAG	-0.013	0.072	-10000	0	-0.25	8	8
CDH1	-0.12	0.2	-10000	0	-0.41	92	92
RhoA/GDP	-0.018	0.09	-10000	0	-0.24	18	18
establishment of polarity of embryonic epithelium	-0.038	0.11	-10000	0	-0.2	79	79
SRC	0.012	0.026	-10000	0	-0.43	1	1
RAC1	0.014	0	-10000	0	-10000	0	0
RHOA	0.014	0	-10000	0	-10000	0	0
EGFR	-0.028	0.12	-10000	0	-0.34	33	33
CASR	-0.015	0.072	-10000	0	-0.27	7	7
RhoA/GTP	-0.006	0.067	-10000	0	-0.29	4	4
AKT2	-0.015	0.082	-10000	0	-0.31	5	5
actin cable formation	-0.043	0.12	-10000	0	-0.22	79	79
apoptosis	0.016	0.081	0.27	8	-10000	0	8
CTNNA1	0.013	0.002	-10000	0	-10000	0	0
mol:GDP	-0.026	0.094	-10000	0	-0.26	19	19
PIP5K1A	-0.039	0.11	-10000	0	-0.21	79	79
PLCG1	-0.013	0.073	-10000	0	-0.26	7	7
Rac1/GTP	-0.047	0.12	-10000	0	-0.32	19	19
homophilic cell adhesion	0	0.002	-10000	0	-10000	0	0

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.031	0.13	-9999	-0.41	30	30
GNB1/GNG2	-0.066	0.14	-9999	-0.36	36	36
mol:DAG	-0.057	0.13	-9999	-0.32	36	36
PLCG1	-0.059	0.14	-9999	-0.33	36	36
YES1	-0.072	0.14	-9999	-0.34	36	36
FZD3	0.012	0.026	-9999	-0.43	1	1
FZD6	-0.021	0.12	-9999	-0.43	22	22
G protein	-0.058	0.14	-9999	-0.34	36	36
MAP3K7	-0.067	0.14	-9999	-0.35	36	36
mol:Ca2+	-0.056	0.13	-9999	-0.32	36	36
mol:IP3	-0.057	0.13	-9999	-0.32	36	36
NLK	0.004	0.012	-9999	-10000	0	0
GNB1	0.014	0	-9999	-10000	0	0
CAMK2A	-0.075	0.14	-9999	-0.35	40	40
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.078	0.14	-9999	-0.26	91	91
CSNK1A1	0.014	0	-9999	-10000	0	0
GNAS	-0.068	0.14	-9999	-0.34	35	35
GO:0007205	-0.057	0.13	-9999	-0.32	36	36
WNT6	-0.016	0.099	-9999	-0.34	23	23
WNT4	-0.063	0.16	-9999	-0.38	54	54
NFAT1/CK1 alpha	-0.068	0.15	-9999	-0.34	43	43
GNG2	-0.004	0.086	-9999	-0.43	11	11
WNT5A	-0.044	0.14	-9999	-0.37	42	42
WNT11	-0.041	0.14	-9999	-0.36	41	41
CDC42	-0.064	0.13	-9999	-0.34	33	33

×

BMP receptor 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
BMP7/BMPR2/BMPR1A-1B/FS	-0.16	0.16	-9999	-0.29	136	136
SMAD6-7/SMURF1	0.025	0.025	-9999	-0.24	2	2
NOG	-0.02	0.095	-9999	-0.31	27	27
SMAD9	-0.042	0.14	-9999	-0.53	17	17
SMAD4	0.014	0	-9999	-10000	0	0
SMAD5	-0.054	0.12	-9999	-0.29	36	36
BMP7/USAG1	-0.17	0.17	-9999	-0.28	178	178
SMAD5/SKI	-0.045	0.12	-9999	-0.29	27	27
SMAD1	0.016	0.05	-9999	-0.31	5	5
BMP2	-0.038	0.13	-9999	-0.35	40	40
SMAD1/SMAD1/SMAD4	-0.003	0.035	-9999	-0.3	1	1
BMPR1A	0.01	0.037	-9999	-0.43	2	2
BMPR1B	-0.12	0.19	-9999	-0.39	92	92
BMPR1A-1B/BAMBI	-0.069	0.14	-9999	-0.24	102	102
AHSG	-0.003	0.049	-9999	-0.31	7	7
CER1	0.004	0.006	-9999	-10000	0	0
BMP2-4/CER1	-0.025	0.097	-9999	-0.27	24	24
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.047	0.12	-9999	-0.3	33	33
BMP2-4 (homodimer)	-0.035	0.11	-9999	-0.25	57	57
RGMB	0.011	0.027	-9999	-0.31	2	2
BMP6/BMPR2/BMPR1A-1B	-0.051	0.12	-9999	-0.23	67	67
RGMA	-0.025	0.11	-9999	-0.36	29	29
SMURF1	0.014	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.057	0.13	-9999	-0.3	38	38
BMP2-4/USAG1	-0.1	0.14	-9999	-0.3	62	62
SMAD6/SMURF1/SMAD5	-0.045	0.12	-9999	-0.29	28	28
SOSTDC1	-0.13	0.17	-9999	-0.34	112	112
BMP7/BMPR2/BMPR1A-1B	-0.12	0.14	-9999	-0.28	92	92
SKI	0.014	0	-9999	-10000	0	0
BMP6 (homodimer)	-0.008	0.08	-9999	-0.31	19	19
HFE2	0.001	0.037	-9999	-0.31	4	4
ZFYVE16	0.009	0.045	-9999	-0.43	3	3
MAP3K7	0.009	0.045	-9999	-0.43	3	3
BMP2-4/CHRD	-0.03	0.11	-9999	-0.21	68	68
SMAD5/SMAD5/SMAD4	-0.045	0.12	-9999	-0.3	23	23
MAPK1	0.014	0	-9999	-10000	0	0
TAK1/TAB family	-0.062	0.097	-9999	-0.29	27	27
BMP7 (homodimer)	-0.13	0.18	-9999	-0.34	116	116
NUP214	0.014	0	-9999	-10000	0	0
BMP6/FETUA	-0.006	0.063	-9999	-0.2	26	26
SMAD1/SKI	0.022	0.049	-9999	-0.29	5	5
SMAD6	0.011	0.032	-9999	-0.37	2	2
CTDSP2	0.014	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.029	0.1	-9999	-0.22	50	50
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.055	0.15	-9999	-0.38	49	49
BMPR2 (homodimer)	0.014	0	-9999	-10000	0	0
GADD34/PP1CA	0.025	0.028	-9999	-0.24	3	3
BMPR1A-1B (homodimer)	-0.076	0.14	-9999	-0.27	92	92
CHRDL1	-0.12	0.19	-9999	-0.39	91	91
ENDOFIN/SMAD1	0.02	0.053	-9999	-0.29	5	5
SMAD6-7/SMURF1/SMAD1	0.033	0.049	-9999	-0.27	5	5
SMAD6/SMURF1	0.014	0	-9999	-10000	0	0
BAMBI	-0.013	0.1	-9999	-0.42	17	17
SMURF2	0.009	0.045	-9999	-0.43	3	3
BMP2-4/CHRDL1	-0.093	0.16	-9999	-0.32	76	76
BMP2-4/GREM1	-0.059	0.13	-9999	-0.29	56	56
SMAD7	0.012	0.026	-9999	-0.43	1	1
SMAD8A/SMAD8A/SMAD4	-0.033	0.13	-9999	-0.49	17	17
SMAD1/SMAD6	0.022	0.049	-9999	-0.29	5	5
TAK1/SMAD6	0.017	0.032	-9999	-0.3	3	3
BMP7	-0.13	0.18	-9999	-0.34	116	116
BMP6	-0.008	0.08	-9999	-0.31	19	19
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.046	0.12	-9999	-0.27	37	37
PPM1A	0.014	0	-9999	-10000	0	0
SMAD1/SMURF2	0.02	0.053	-9999	-0.28	6	6
SMAD7/SMURF1	0.019	0.019	-9999	-0.3	1	1
CTDSPL	0.014	0	-9999	-10000	0	0
PPP1CA	0.014	0	-9999	-10000	0	0
XIAP	0.01	0.037	-9999	-0.43	2	2
CTDSP1	0.014	0	-9999	-10000	0	0
PPP1R15A	0.014	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.099	0.16	-9999	-0.37	53	53
CHRD	-0.005	0.082	-9999	-0.36	14	14
BMPR2	0.014	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.062	0.13	-9999	-0.32	37	37
BMP4	-0.014	0.099	-9999	-0.36	21	21
FST	-0.098	0.17	-9999	-0.36	85	85
BMP2-4/NOG	-0.038	0.11	-9999	-0.28	31	31
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.1	0.14	-9999	-0.26	92	92

×

a4b1 and a4b7 Integrin signaling

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
ITGB1	0.011	0.032	-9999	-0.37	2	2
ITGB7	-0.017	0.11	-9999	-0.42	20	20
ITGA4	-0.038	0.14	-9999	-0.39	36	36
alpha4/beta7 Integrin	-0.038	0.12	-9999	-0.29	53	53
alpha4/beta1 Integrin	-0.018	0.1	-9999	-0.27	37	37

×

Endothelins

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
AKT1	-0.001	0.17	0.27	23	-0.45	18	41
PTK2B	0.01	0.038	-10000	0	-0.35	3	3
mol:Ca2+	0.015	0.17	-10000	0	-0.79	7	7
EDN1	0.001	0.13	0.21	22	-0.4	15	37
EDN3	-0.12	0.18	-10000	0	-0.36	96	96
EDN2	-0.005	0.064	-10000	0	-0.31	12	12
HRAS/GDP	-0.004	0.16	0.2	11	-0.4	25	36
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.006	0.14	0.18	14	-0.39	23	37
ADCY4	-0.045	0.15	0.18	12	-0.36	34	46
ADCY5	-0.083	0.17	0.18	9	-0.36	55	64
ADCY6	-0.044	0.15	0.18	13	-0.36	33	46
ADCY7	-0.044	0.15	0.18	12	-0.37	32	44
ADCY1	-0.078	0.16	0.18	7	-0.36	49	56
ADCY2	-0.13	0.17	0.18	5	-0.36	77	82
ADCY3	-0.043	0.15	0.18	13	-0.36	32	45
ADCY8	-0.059	0.16	0.18	4	-0.37	36	40
ADCY9	-0.043	0.15	0.18	13	-0.36	31	44
arachidonic acid secretion	0.007	0.14	-10000	0	-0.4	16	16
ETB receptor/Endothelin-1/Gq/GTP	0.002	0.097	-10000	0	-0.27	20	20
GNAO1	-0.066	0.17	-10000	0	-0.42	52	52
HRAS	0.014	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	0.037	0.18	0.33	32	-0.41	18	50
ETA receptor/Endothelin-1/Gs/GTP	-0.008	0.19	0.3	28	-0.37	35	63
mol:GTP	0.002	0.002	-10000	0	-10000	0	0
COL3A1	-0.013	0.2	0.27	21	-0.52	23	44
EDNRB	-0.005	0.086	-10000	0	-0.42	11	11
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.037	0.22	0.27	22	-0.53	32	54
CYSLTR1	-0.017	0.2	0.27	23	-0.53	24	47
SLC9A1	0.01	0.1	0.19	23	-0.26	15	38
mol:GDP	-0.012	0.16	0.2	11	-0.43	25	36
SLC9A3	-0.039	0.21	-10000	0	-0.55	32	32
RAF1	-0.005	0.14	-10000	0	-0.42	19	19
JUN	0.023	0.14	-10000	0	-0.57	8	8
JAK2	-0.007	0.18	0.27	23	-0.48	19	42
mol:IP3	-0.009	0.14	-10000	0	-0.4	22	22
ETA receptor/Endothelin-1	0.025	0.22	0.39	32	-0.52	18	50
PLCB1	-0.033	0.13	-10000	0	-0.41	31	31
PLCB2	0.003	0.069	-10000	0	-0.43	7	7
ETA receptor/Endothelin-3	-0.081	0.16	0.16	7	-0.26	104	111
FOS	0.014	0.12	-10000	0	-0.42	8	8
Gai/GDP	-0.097	0.25	-10000	0	-0.62	48	48
CRK	0.014	0	-10000	0	-10000	0	0
mol:Ca ++	-0.019	0.19	0.24	14	-0.53	24	38
BCAR1	0.009	0.045	-10000	0	-0.43	3	3
PRKCB1	-0.008	0.13	-10000	0	-0.38	22	22
GNAQ	0.015	0.003	-10000	0	-10000	0	0
GNAZ	-0.029	0.13	-10000	0	-0.42	28	28
GNAL	-0.074	0.16	-10000	0	-0.35	67	67
Gs family/GDP	-0.054	0.15	-10000	0	-0.39	33	33
ETA receptor/Endothelin-1/Gq/GTP	0.009	0.13	0.2	18	-0.32	22	40
MAPK14	-0.005	0.11	-10000	0	-0.35	17	17
TRPC6	0.013	0.18	-10000	0	-0.85	7	7
GNAI2	0.014	0	-10000	0	-10000	0	0
GNAI3	0.014	0	-10000	0	-10000	0	0
GNAI1	0.006	0.056	-10000	0	-0.4	5	5
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.01	0.12	-10000	0	-0.36	19	19
ETB receptor/Endothelin-2	-0.005	0.076	-10000	0	-0.25	22	22
ETB receptor/Endothelin-3	-0.083	0.14	-10000	0	-0.25	103	103
ETB receptor/Endothelin-1	0.002	0.12	-10000	0	-0.35	19	19
MAPK3	0.01	0.13	-10000	0	-0.45	12	12
MAPK1	0.01	0.13	-10000	0	-0.45	12	12
Rac1/GDP	-0.004	0.16	0.19	11	-0.4	25	36
cAMP biosynthetic process	-0.1	0.17	0.19	3	-0.38	56	59
MAPK8	0.013	0.17	-10000	0	-0.58	12	12
SRC	0.012	0.026	-10000	0	-0.43	1	1
ETB receptor/Endothelin-1/Gi/GTP	-0.036	0.12	-10000	0	-0.31	27	27
p130Cas/CRK/Src/PYK2	-0.002	0.16	-10000	0	-0.53	15	15
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.004	0.16	0.19	11	-0.4	25	36
COL1A2	-0.018	0.23	0.27	20	-0.67	20	40
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.003	0.11	0.16	10	-0.25	28	38
mol:DAG	-0.009	0.14	-10000	0	-0.4	22	22
MAP2K2	0.004	0.13	-10000	0	-0.44	14	14
MAP2K1	0.004	0.13	-10000	0	-0.44	14	14
EDNRA	-0.002	0.14	0.21	23	-0.38	20	43
positive regulation of muscle contraction	0.007	0.14	0.23	23	-0.4	17	40
Gq family/GDP	-0.042	0.13	-10000	0	-0.44	20	20
HRAS/GTP	-0.014	0.15	-10000	0	-0.42	22	22
PRKCH	-0.004	0.14	-10000	0	-0.39	21	21
RAC1	0.014	0	-10000	0	-10000	0	0
PRKCA	-0.01	0.14	-10000	0	-0.36	26	26
PRKCB	-0.03	0.17	-10000	0	-0.39	35	35
PRKCE	-0.002	0.13	-10000	0	-0.38	21	21
PRKCD	-0.002	0.13	-10000	0	-0.39	20	20
PRKCG	-0.008	0.14	-10000	0	-0.39	21	21
regulation of vascular smooth muscle contraction	0.013	0.13	-10000	0	-0.5	8	8
PRKCQ	-0.037	0.17	-10000	0	-0.38	37	37
PLA2G4A	0.005	0.14	-10000	0	-0.43	16	16
GNA14	-0.025	0.11	-10000	0	-0.32	34	34
GNA15	-0.004	0.086	-10000	0	-0.38	14	14
GNA12	0.014	0	-10000	0	-10000	0	0
GNA11	0.013	0.026	-10000	0	-0.43	1	1
Rac1/GTP	0.037	0.18	0.33	32	-0.42	17	49
MMP1	-0.14	0.3	0.26	2	-0.5	90	92

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.027	0.12	-9999	-0.27	44	44
NF kappa B1 p50/RelA/I kappa B alpha	-0.025	0.1	-9999	-0.29	14	14
AP1	-0.084	0.11	-9999	-0.31	36	36
mol:PIP3	-0.089	0.11	-9999	-0.31	41	41
AKT1	0.006	0.091	-9999	-0.36	8	8
PTK2B	-0.028	0.098	-9999	-0.29	23	23
RHOA	0.006	0.047	-9999	-0.27	2	2
PIK3CB	0.014	0.001	-9999	-10000	0	0
mol:Ca2+	-0.031	0.091	-9999	-0.21	44	44
MAGI3	0.009	0.045	-9999	-0.43	3	3
RELA	0.014	0	-9999	-10000	0	0
apoptosis	-0.075	0.13	-9999	-0.27	70	70
HRAS/GDP	0.01	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	-0.037	0.11	-9999	-0.27	30	30
NF kappa B1 p50/RelA	-0.071	0.11	-9999	-0.36	20	20
endothelial cell migration	-0.054	0.17	-9999	-0.39	47	47
ADCY4	-0.068	0.15	-9999	-0.37	40	40
ADCY5	-0.092	0.17	-9999	-0.39	54	54
ADCY6	-0.068	0.15	-9999	-0.38	40	40
ADCY7	-0.068	0.15	-9999	-0.36	45	45
ADCY1	-0.099	0.18	-9999	-0.37	63	63
ADCY2	-0.13	0.18	-9999	-0.4	69	69
ADCY3	-0.067	0.15	-9999	-0.36	43	43
ADCY8	-0.073	0.15	-9999	-0.35	45	45
ADCY9	-0.066	0.15	-9999	-0.38	37	37
GSK3B	-0.021	0.094	-9999	-0.28	22	22
arachidonic acid secretion	-0.066	0.14	-9999	-0.36	38	38
GNG2	-0.004	0.086	-9999	-0.43	11	11
TRIP6	0.007	0.062	-9999	-0.34	7	7
GNAO1	-0.079	0.14	-9999	-0.27	83	83
HRAS	0.014	0	-9999	-10000	0	0
NFKBIA	-0.04	0.11	-9999	-0.26	44	44
GAB1	0.01	0.037	-9999	-0.43	2	2
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.029	0.21	-9999	-0.87	17	17
JUN	0.013	0	-9999	-10000	0	0
LPA/LPA2/NHERF2	0.008	0.044	-9999	-0.23	7	7
TIAM1	-0.058	0.24	-9999	-1	17	17
PIK3R1	0.01	0.037	-9999	-0.43	2	2
mol:IP3	-0.031	0.092	-9999	-0.21	44	44
PLCB3	0.012	0.039	-9999	-0.22	5	5
FOS	0.006	0.05	-9999	-0.31	7	7
positive regulation of mitosis	-0.066	0.14	-9999	-0.36	38	38
LPA/LPA1-2-3	-0.082	0.14	-9999	-0.28	73	73
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.009	0.045	-9999	-0.43	3	3
stress fiber formation	-0.04	0.11	-9999	-0.32	23	23
GNAZ	-0.056	0.14	-9999	-0.29	61	61
EGFR/PI3K-beta/Gab1	-0.093	0.12	-9999	-0.32	41	41
positive regulation of dendritic cell cytokine production	-0.082	0.14	-9999	-0.28	73	73
LPA/LPA2/MAGI-3	0.007	0.047	-9999	-0.24	8	8
ARHGEF1	-0.015	0.099	-9999	-0.23	37	37
GNAI2	-0.031	0.12	-9999	-0.29	37	37
GNAI3	-0.031	0.12	-9999	-0.29	37	37
GNAI1	-0.036	0.12	-9999	-0.3	39	39
LPA/LPA3	-0.074	0.12	-9999	-0.25	86	86
LPA/LPA2	0	0.047	-9999	-0.29	5	5
LPA/LPA1	-0.046	0.14	-9999	-0.3	52	52
HB-EGF/EGFR	-0.049	0.12	-9999	-0.26	49	49
HBEGF	-0.04	0.11	-9999	-0.25	62	62
mol:DAG	-0.031	0.092	-9999	-0.21	44	44
cAMP biosynthetic process	-0.089	0.16	-9999	-0.35	57	57
NFKB1	0.014	0	-9999	-10000	0	0
SRC	0.012	0.026	-9999	-0.43	1	1
GNB1	0.014	0.001	-9999	-10000	0	0
LYN	-0.041	0.12	-9999	-0.27	42	42
GNAQ	-0.042	0.093	-9999	-0.23	41	41
LPAR2	0.006	0.056	-9999	-0.4	5	5
LPAR3	-0.1	0.17	-9999	-0.36	86	86
LPAR1	-0.055	0.16	-9999	-0.41	41	41
IL8	-0.092	0.17	-9999	-0.4	51	51
PTK2	-0.073	0.13	-9999	-0.26	68	68
Rac1/GDP	0.01	0	-9999	-10000	0	0
CASP3	-0.075	0.14	-9999	-0.27	70	70
EGFR	-0.028	0.12	-9999	-0.34	33	33
PLCG1	-0.046	0.1	-9999	-0.26	44	44
PLD2	-0.073	0.13	-9999	-0.26	67	67
G12/G13	-0.018	0.11	-9999	-0.26	37	37
PI3K-beta	-0.036	0.084	-9999	-0.35	12	12
cell migration	-0.023	0.086	-9999	-0.25	22	22
SLC9A3R2	0.011	0.032	-9999	-0.37	2	2
PXN	-0.041	0.11	-9999	-0.33	23	23
HRAS/GTP	-0.068	0.15	-9999	-0.37	38	38
RAC1	0.014	0	-9999	-10000	0	0
MMP9	-0.068	0.16	-9999	-0.38	59	59
PRKCE	0.013	0	-9999	-10000	0	0
PRKCD	-0.025	0.088	-9999	-0.26	12	12
Gi(beta/gamma)	-0.066	0.15	-9999	-0.37	38	38
mol:LPA	-0.009	0.039	-9999	-0.17	10	10
TRIP6/p130 Cas/FAK1/Paxillin	-0.053	0.14	-9999	-0.37	26	26
MAPKKK cascade	-0.066	0.14	-9999	-0.36	38	38
contractile ring contraction involved in cytokinesis	0.006	0.047	-9999	-0.27	2	2
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.059	0.1	-9999	-0.25	49	49
GNA15	-0.052	0.11	-9999	-0.24	53	53
GNA12	0.014	0	-9999	-10000	0	0
GNA13	0.014	0	-9999	-10000	0	0
MAPT	-0.039	0.11	-9999	-0.28	30	30
GNA11	-0.043	0.094	-9999	-0.23	44	44
Rac1/GTP	-0.031	0.23	-9999	-0.92	17	17
MMP2	-0.054	0.17	-9999	-0.39	47	47

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.014	0	-9999	-10000	0	0
EGFR	-0.028	0.12	-9999	-0.34	33	33
EGF/EGFR	-0.063	0.12	-9999	-0.23	82	82
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.038	0.11	-9999	-0.21	65	65
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.007	0.086	-9999	-0.35	16	16
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.097	0.18	-9999	-0.4	76	76
EGF/EGFR dimer/SHC	-0.063	0.13	-9999	-0.26	66	66
mol:GDP	-0.04	0.11	-9999	-0.21	65	65
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.003	0.08	-9999	-0.38	12	12
GRB2/SOS1	0.02	0	-9999	-10000	0	0
HRAS/GTP	-0.057	0.084	-9999	-0.3	10	10
SHC1	0.014	0	-9999	-10000	0	0
HRAS/GDP	-0.035	0.1	-9999	-0.3	10	10
FRAP1	-0.043	0.1	-9999	-0.2	65	65
EGF/EGFR dimer	-0.086	0.15	-9999	-0.28	99	99
SOS1	0.014	0	-9999	-10000	0	0
GRB2	0.014	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.006	0.085	-9999	-0.26	26	26

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	-0.039	0.15	-10000	0	-0.32	50	50
ACTA1	-0.059	0.18	0.17	8	-0.4	50	58
NUMA1	-0.039	0.15	-10000	0	-0.38	36	36
SPTAN1	-0.055	0.18	0.17	8	-0.39	50	58
LIMK1	-0.055	0.18	0.17	7	-0.39	50	57
BIRC3	-0.052	0.15	-10000	0	-0.38	47	47
BIRC2	0.003	0.066	-10000	0	-0.41	7	7
BAX	0.014	0	-10000	0	-10000	0	0
CASP10	-0.07	0.17	-10000	0	-0.36	59	59
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.01	0.037	-10000	0	-0.43	2	2
PTK2	-0.039	0.15	-10000	0	-0.32	50	50
DIABLO	0.014	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.054	0.18	0.17	8	-0.39	50	58
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.011	0.027	-10000	0	-0.31	2	2
GSN	-0.056	0.19	0.17	7	-0.4	50	57
MADD	0.014	0	-10000	0	-10000	0	0
TFAP2A	-0.074	0.22	-10000	0	-0.57	42	42
BID	-0.033	0.097	-10000	0	-0.2	59	59
MAP3K1	-0.022	0.088	-10000	0	-0.23	29	29
TRADD	0.014	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.016	0.037	-10000	0	-0.3	4	4
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.059	0.2	0.17	8	-0.41	51	59
CASP9	0.014	0	-10000	0	-10000	0	0
DNA repair	-0.005	0.056	0.14	10	-0.17	12	22
neuron apoptosis	-0.027	0.15	-10000	0	-0.6	18	18
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.046	0.18	0.17	1	-0.38	50	51
APAF1	0.007	0.052	-10000	0	-0.43	4	4
CASP6	-0.016	0.1	-10000	0	-0.31	21	21
TRAF2	0.014	0	-10000	0	-10000	0	0
ICAD/CAD	-0.048	0.18	0.17	6	-0.38	50	56
CASP7	0.035	0.093	0.29	28	-10000	0	28
KRT18	-0.058	0.18	-10000	0	-0.58	28	28
apoptosis	-0.034	0.15	0.18	6	-0.37	35	41
DFFA	-0.055	0.18	0.17	7	-0.39	50	57
DFFB	-0.055	0.18	0.17	8	-0.39	50	58
PARP1	0.005	0.056	0.17	12	-0.14	10	22
actin filament polymerization	0.047	0.17	0.36	50	-0.17	6	56
TNF	-0.021	0.11	-10000	0	-0.38	25	25
CYCS	-0.023	0.07	-10000	0	-0.18	30	30
SATB1	-0.031	0.13	-10000	0	-0.4	18	18
SLK	-0.058	0.18	0.17	8	-0.39	52	60
p15 BID/BAX	-0.023	0.088	-10000	0	-0.26	22	22
CASP2	0.004	0.081	-10000	0	-0.31	9	9
JNK cascade	0.022	0.087	0.23	29	-10000	0	29
CASP3	-0.064	0.19	0.17	8	-0.41	53	61
LMNB2	0.003	0.075	-10000	0	-0.25	14	14
RIPK1	0.014	0	-10000	0	-10000	0	0
CASP4	0.01	0.037	-10000	0	-0.43	2	2
Mammalian IAPs/DIABLO	-0.008	0.1	-10000	0	-0.26	31	31
negative regulation of DNA binding	-0.073	0.22	-10000	0	-0.57	42	42
stress fiber formation	-0.057	0.18	0.17	8	-0.38	52	60
GZMB	-0.086	0.19	-10000	0	-0.37	77	77
CASP1	-0.006	0.08	-10000	0	-0.31	17	17
LMNB1	0.003	0.075	-10000	0	-0.25	14	14
APP	-0.028	0.16	-10000	0	-0.61	18	18
TNFRSF1A	0.014	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.008	0.019	-10000	0	-0.3	1	1
VIM	-0.033	0.15	0.19	8	-0.36	34	42
LMNA	0.003	0.075	-10000	0	-0.28	10	10
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.001	0.085	-10000	0	-0.33	9	9
LRDD	0.003	0.069	-10000	0	-0.43	7	7
SREBF1	-0.056	0.18	0.17	8	-0.39	51	59
APAF-1/Caspase 9	0.008	0.068	0.36	6	-10000	0	6
nuclear fragmentation during apoptosis	-0.038	0.15	-10000	0	-0.37	36	36
CFL2	-0.049	0.18	0.18	1	-0.37	50	51
GAS2	-0.091	0.19	0.17	7	-0.36	70	77
positive regulation of apoptosis	0.007	0.075	-10000	0	-0.28	10	10
PRF1	-0.057	0.15	-10000	0	-0.37	52	52

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.096	0.14	-10000	0	-0.28	102	102
TP53	-0.041	0.066	0.17	2	-0.29	4	6
Senescence	-0.041	0.066	0.17	2	-0.29	4	6
Apoptosis	-0.041	0.066	0.17	2	-0.29	4	6
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.066	0.097	0.21	77	-0.24	3	80
MDM4	0.012	0.026	-10000	0	-0.43	1	1

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.031	0.069	0.2	35	-0.17	1	36
RFC1	0.031	0.069	0.2	35	-0.17	1	36
PRKDC	0.031	0.069	0.2	35	-0.17	1	36
RIPK1	0.014	0.002	-10000	0	-10000	0	0
CASP7	0.025	0.072	0.22	18	-0.31	1	19
FASLG/FAS/FADD/FAF1	-0.004	0.11	0.19	30	-0.25	33	63
MAP2K4	-0.008	0.12	-10000	0	-0.36	16	16
mol:ceramide	-0.028	0.13	-10000	0	-0.3	46	46
GSN	0.031	0.071	0.2	35	-0.2	2	37
FASLG/FAS/FADD/FAF1/Caspase 8	-0.008	0.12	0.18	11	-0.28	36	47
FAS	0.006	0.058	-10000	0	-0.43	5	5
BID	0.039	0.085	0.28	31	-0.25	1	32
MAP3K1	0.013	0.087	0.2	17	-0.24	10	27
MAP3K7	0.009	0.046	-10000	0	-0.43	3	3
RB1	0.027	0.077	0.2	35	-0.22	6	41
CFLAR	0.012	0.026	-10000	0	-0.43	1	1
HGF/MET	-0.047	0.13	-10000	0	-0.24	79	79
ARHGDIB	0.027	0.078	0.2	35	-0.23	6	41
FADD	0.012	0.019	-10000	0	-0.3	1	1
actin filament polymerization	-0.031	0.071	0.2	2	-0.2	35	37
NFKB1	-0.021	0.046	-10000	0	-0.26	4	4
MAPK8	-0.009	0.14	-10000	0	-0.44	16	16
DFFA	0.031	0.069	0.2	35	-0.17	1	36
DNA fragmentation during apoptosis	0.031	0.069	0.2	35	-0.17	1	36
FAS/FADD/MET	-0.017	0.097	-10000	0	-0.22	50	50
CFLAR/RIP1	0.018	0.019	-10000	0	-0.3	1	1
FAIM3	-0.046	0.15	-10000	0	-0.4	41	41
FAF1	0.013	0.005	-10000	0	-10000	0	0
PARP1	0.031	0.069	0.2	35	-0.17	1	36
DFFB	0.031	0.069	0.2	35	-0.17	1	36
CHUK	-0.001	0.049	-10000	0	-0.25	1	1
FASLG	-0.083	0.18	-10000	0	-0.39	67	67
FAS/FADD	0.014	0.044	-10000	0	-0.28	6	6
HGF	-0.025	0.11	-10000	0	-0.36	29	29
LMNA	0.034	0.061	0.19	35	-10000	0	35
CASP6	0.031	0.069	0.2	35	-0.17	1	36
CASP10	0.007	0.053	-10000	0	-0.43	4	4
CASP3	0.031	0.085	0.24	35	-0.2	1	36
PTPN13	-0.01	0.099	-10000	0	-0.43	15	15
CASP8	0.041	0.11	0.34	31	-0.31	1	32
IL6	-0.031	0.22	-10000	0	-1.2	8	8
MET	-0.051	0.15	-10000	0	-0.4	44	44
ICAD/CAD	0.034	0.062	0.19	35	-10000	0	35
FASLG/FAS/FADD/FAF1/Caspase 10	-0.028	0.13	-10000	0	-0.3	46	46
activation of caspase activity by cytochrome c	0.039	0.085	0.27	31	-0.25	1	32
PAK2	0.031	0.069	0.2	35	-0.17	1	36
BCL2	0.001	0.074	-10000	0	-0.43	8	8

×

Calcium signaling in the CD4+ TCR 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
NFATC1	-0.012	0.056	-9999	-0.28	8	8
NFATC2	-0.032	0.088	-9999	-0.26	30	30
NFATC3	-0.004	0.032	-9999	-10000	0	0
CD40LG	-0.16	0.27	-9999	-0.52	78	78
PTGS2	-0.15	0.26	-9999	-0.48	88	88
JUNB	0.012	0.019	-9999	-0.31	1	1
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.004	0.02	-9999	-10000	0	0
CaM/Ca2+	-0.004	0.02	-9999	-10000	0	0
CALM1	0.007	0.011	-9999	-10000	0	0
JUN	0.007	0.012	-9999	-10000	0	0
mol:Ca2+	-0.009	0.013	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.004	0.013	-9999	-0.18	1	1
FOSL1	-0.048	0.14	-9999	-0.38	44	44
CREM	0.012	0.019	-9999	-0.31	1	1
Jun/NFAT1-c-4/p21SNFT	-0.076	0.16	-9999	-0.34	53	53
FOS	-0.001	0.052	-9999	-0.32	7	7
IFNG	-0.17	0.28	-9999	-0.5	101	101
AP-1/NFAT1-c-4	-0.15	0.28	-9999	-0.54	77	77
FASLG	-0.17	0.29	-9999	-0.54	91	91
NFAT1-c-4/ICER1	-0.046	0.12	-9999	-0.32	25	25
IL2RA	-0.15	0.27	-9999	-0.53	73	73
FKBP12/FK506	0.009	0.013	-9999	-0.21	1	1
CSF2	-0.14	0.24	-9999	-0.48	70	70
JunB/Fra1/NFAT1-c-4	-0.067	0.13	-9999	-0.32	39	39
IL4	-0.14	0.23	-9999	-0.47	72	72
IL2	-0.006	0.022	-9999	-10000	0	0
IL3	-0.016	0.02	-9999	-10000	0	0
FKBP1A	0.012	0.019	-9999	-0.31	1	1
BATF3	0.003	0.064	-9999	-0.37	8	8
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.014	0.001	-9999	-10000	0	0

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.011	0.029	-9999	-0.2	5	5
ADCY5	-0.037	0.093	-9999	-0.2	69	69
ADCY6	0.013	0.025	-9999	-0.22	3	3
ADCY7	0.012	0.027	-9999	-0.25	3	3
ADCY1	-0.031	0.099	-9999	-0.24	50	50
ADCY2	-0.097	0.12	-9999	-0.21	142	142
ADCY3	0.014	0.016	-9999	-0.25	1	1
ADCY8	-0.007	0.054	-9999	-0.16	29	29
PRKCE	0.01	0	-9999	-10000	0	0
ADCY9	0.014	0.016	-9999	-0.25	1	1
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.054	0.066	-9999	-0.2	19	19

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.036	0.19	-10000	0	-0.55	25	25
IHH	-0.002	0.057	-10000	0	-0.33	4	4
SHH Np/Cholesterol/GAS1	0.002	0.054	-10000	0	-0.18	22	22
LRPAP1	0.014	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	-0.002	0.053	0.18	22	-10000	0	22
SMO/beta Arrestin2	-0.032	0.15	-10000	0	-0.47	16	16
SMO	-0.041	0.16	-10000	0	-0.5	16	16
AKT1	-0.006	0.084	-10000	0	-0.3	5	5
ARRB2	0.014	0	-10000	0	-10000	0	0
BOC	-0.015	0.1	-10000	0	-0.36	21	21
ADRBK1	0.012	0.026	-10000	0	-0.43	1	1
heart looping	-0.04	0.15	-10000	0	-0.49	16	16
STIL	-0.008	0.1	-10000	0	-0.37	10	10
DHH N/PTCH2	-0.033	0.11	-10000	0	-0.25	55	55
DHH N/PTCH1	-0.036	0.14	-10000	0	-0.39	20	20
PIK3CA	0.007	0.052	-10000	0	-0.43	4	4
DHH	-0.045	0.14	-10000	0	-0.35	46	46
PTHLH	-0.05	0.24	-10000	0	-0.77	23	23
determination of left/right symmetry	-0.04	0.15	-10000	0	-0.49	16	16
PIK3R1	0.01	0.037	-10000	0	-0.43	2	2
skeletal system development	-0.049	0.24	-10000	0	-0.73	25	25
IHH N/Hhip	-0.008	0.073	-10000	0	-0.24	21	21
DHH N/Hhip	-0.039	0.11	-10000	0	-0.24	62	62
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.04	0.15	-10000	0	-0.49	16	16
pancreas development	-0.013	0.081	-10000	0	-0.31	20	20
HHAT	0.006	0.058	-10000	0	-0.43	5	5
PI3K	0.014	0.05	-10000	0	-0.35	5	5
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	0.005	0.061	-10000	0	-0.41	6	6
somite specification	-0.04	0.15	-10000	0	-0.49	16	16
SHH Np/Cholesterol/PTCH1	-0.012	0.1	-10000	0	-0.39	10	10
SHH Np/Cholesterol/PTCH2	-0.002	0.061	-10000	0	-0.18	28	28
SHH Np/Cholesterol/Megalin	-0.11	0.11	-10000	0	-0.19	171	171
SHH	-0.002	0.058	-10000	0	-0.23	16	16
catabolic process	-0.014	0.12	-10000	0	-0.37	21	21
SMO/Vitamin D3	-0.024	0.12	-10000	0	-0.4	17	17
SHH Np/Cholesterol/Hhip	-0.007	0.063	-10000	0	-0.18	32	32
LRP2	-0.21	0.19	-10000	0	-0.37	164	164
receptor-mediated endocytosis	-0.097	0.15	-10000	0	-0.46	24	24
SHH Np/Cholesterol/BOC	-0.008	0.069	-10000	0	-0.18	36	36
SHH Np/Cholesterol/CDO	0.004	0.049	-10000	0	-0.18	19	19
mesenchymal cell differentiation	0.007	0.063	0.17	32	-10000	0	32
mol:Vitamin D3	-0.01	0.11	-10000	0	-0.39	10	10
IHH N/PTCH2	-0.001	0.072	-10000	0	-0.29	14	14
CDON	0.009	0.045	-10000	0	-0.43	3	3
IHH N/PTCH1	-0.012	0.13	-10000	0	-0.37	21	21
Megalin/LRPAP1	-0.14	0.14	-10000	0	-0.25	164	164
PTCH2	-0.004	0.08	-10000	0	-0.36	13	13
SHH Np/Cholesterol	0	0.043	-10000	0	-0.17	16	16
PTCH1	-0.014	0.12	-10000	0	-0.37	21	21
HHIP	-0.013	0.081	-10000	0	-0.31	20	20

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.009	0.045	-9999	-0.43	3	3
alphaV beta3 Integrin	-0.044	0.13	-9999	-0.3	57	57
PTK2	-0.047	0.16	-9999	-0.39	42	42
positive regulation of JNK cascade	-0.047	0.1	-9999	-0.29	44	44
CDC42/GDP	-0.028	0.16	-9999	-0.38	43	43
Rac1/GDP	-0.027	0.16	-9999	-0.38	43	43
RAP1B	0.012	0.019	-9999	-0.31	1	1
RAP1A	0.014	0	-9999	-10000	0	0
CTNNB1	0.014	0	-9999	-10000	0	0
CDC42/GTP	-0.056	0.13	-9999	-0.35	44	44
nectin-3/I-afadin	-0.034	0.12	-9999	-0.3	47	47
RAPGEF1	-0.037	0.17	-9999	-0.42	44	44
mol:GTP	0	0	-9999	-10000	0	0
CRK	-0.05	0.19	-9999	-0.48	44	44
PDGFB-D/PDGFRB	0.009	0.045	-9999	-0.43	3	3
TLN1	0	0.06	-9999	-0.23	4	4
Rap1/GTP	-0.049	0.11	-9999	-0.3	43	43
IQGAP1	0.014	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.022	0.032	-9999	-0.22	4	4
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.034	0.12	-9999	-0.3	47	47
PVR	0.009	0.045	-9999	-0.43	3	3
Necl-5(dimer)	0.009	0.045	-9999	-0.43	3	3
mol:GDP	-0.044	0.19	-9999	-0.47	43	43
MLLT4	0.006	0.056	-9999	-0.4	5	5
PIK3CA	0.007	0.052	-9999	-0.43	4	4
PI3K	-0.006	0.11	-9999	-0.23	45	45
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.009	0.052	-9999	-0.23	12	12
positive regulation of lamellipodium assembly	-0.054	0.11	-9999	-0.3	49	49
PVRL1	0.006	0.05	-9999	-0.31	7	7
PVRL3	-0.055	0.16	-9999	-0.42	45	45
PVRL2	0.014	0	-9999	-10000	0	0
PIK3R1	0.01	0.037	-9999	-0.43	2	2
CDH1	-0.12	0.2	-9999	-0.41	92	92
CLDN1	-0.13	0.19	-9999	-0.36	104	104
JAM-A/CLDN1	-0.084	0.14	-9999	-0.27	83	83
SRC	-0.062	0.21	-9999	-0.53	44	44
ITGB3	-0.068	0.17	-9999	-0.4	55	55
nectin-1(dimer)/I-afadin/I-afadin	0.009	0.052	-9999	-0.23	12	12
FARP2	-0.044	0.18	-9999	-0.46	44	44
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)	-0.021	0.11	-9999	-0.26	45	45
nectin-1/I-afadin	0.009	0.052	-9999	-0.23	12	12
nectin-2/I-afadin	0.015	0.04	-9999	-0.28	5	5
RAC1/GTP/IQGAP1/filamentous actin	0.018	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.023	0.11	-9999	-0.26	42	42
CDC42/GTP/IQGAP1/filamentous actin	0.018	0	-9999	-10000	0	0
F11R	0.009	0.045	-9999	-0.43	3	3
positive regulation of filopodium formation	-0.047	0.1	-9999	-0.29	44	44
alphaV/beta3 Integrin/Talin	-0.028	0.11	-9999	-0.38	12	12
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.015	0.04	-9999	-0.28	5	5
nectin-2(dimer)/I-afadin/I-afadin	0.015	0.04	-9999	-0.28	5	5
PIP5K1C	-0.007	0.065	-9999	-0.15	43	43
VAV2	-0.054	0.2	-9999	-0.48	48	48
RAP1/GDP	-0.024	0.15	-9999	-0.36	43	43
ITGAV	0.003	0.069	-9999	-0.43	7	7
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.018	0.11	-9999	-0.26	42	42
nectin-3(dimer)/I-afadin/I-afadin	-0.034	0.12	-9999	-0.3	47	47
Rac1/GTP	-0.064	0.14	-9999	-0.36	48	48
PTPRM	-0.014	0.072	-9999	-0.18	43	43
E-cadherin/beta catenin/alpha catenin	-0.036	0.1	-9999	-0.32	2	2
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.014	0	-9999	-10000	0	0

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.063	0.26	-9999	-0.74	29	29
MKNK1	0.014	0	-9999	-10000	0	0
MAPK14	-0.013	0.095	-9999	-0.28	25	25
ATF2/c-Jun	0	0.091	-9999	-0.4	6	6
MAPK11	-0.02	0.11	-9999	-0.31	29	29
MITF	-0.046	0.15	-9999	-0.32	60	60
MAPKAPK5	-0.012	0.12	-9999	-0.33	29	29
KRT8	-0.065	0.17	-9999	-0.35	57	57
MAPKAPK3	0.014	0	-9999	-10000	0	0
MAPKAPK2	0.014	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.023	0.14	-9999	-0.39	32	32
CEBPB	-0.012	0.12	-9999	-0.33	29	29
SLC9A1	-0.012	0.12	-9999	-0.33	29	29
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.012	0.13	-9999	-0.34	31	31
p38alpha-beta/MNK1	-0.006	0.12	-9999	-0.33	26	26
JUN	0	0.09	-9999	-0.4	6	6
PPARGC1A	-0.095	0.18	-9999	-0.32	93	93
USF1	-0.012	0.12	-9999	-0.33	29	29
RAB5/GDP/GDI1	-0.005	0.085	-9999	-0.24	26	26
NOS2	-0.04	0.21	-9999	-0.87	12	12
DDIT3	-0.013	0.12	-9999	-0.33	29	29
RAB5A	0.014	0	-9999	-10000	0	0
HSPB1	-0.004	0.096	-9999	-0.27	26	26
p38alpha-beta/HBP1	-0.006	0.12	-9999	-0.33	26	26
CREB1	-0.013	0.13	-9999	-0.37	29	29
RAB5/GDP	0.01	0	-9999	-10000	0	0
EIF4E	-0.006	0.1	-9999	-0.29	27	27
RPS6KA4	-0.012	0.12	-9999	-0.33	29	29
PLA2G4A	-0.018	0.12	-9999	-0.29	38	38
GDI1	-0.012	0.12	-9999	-0.33	29	29
TP53	-0.023	0.14	-9999	-0.4	30	30
RPS6KA5	-0.018	0.13	-9999	-0.35	32	32
ESR1	-0.027	0.15	-9999	-0.37	37	37
HBP1	0.014	0	-9999	-10000	0	0
MEF2C	-0.018	0.13	-9999	-0.36	32	32
MEF2A	-0.015	0.13	-9999	-0.36	29	29
EIF4EBP1	-0.013	0.13	-9999	-0.37	29	29
KRT19	-0.055	0.15	-9999	-0.36	43	43
ELK4	-0.012	0.12	-9999	-0.33	29	29
ATF6	-0.012	0.12	-9999	-0.33	29	29
ATF1	-0.013	0.13	-9999	-0.37	29	29
p38alpha-beta/MAPKAPK2	-0.006	0.12	-9999	-0.33	26	26
p38alpha-beta/MAPKAPK3	-0.006	0.12	-9999	-0.32	29	29

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	0.008	0.053	-9999	-0.21	15	15
alphaV beta3 Integrin	-0.079	0.17	-9999	-0.32	78	78
PTK2	-0.079	0.18	-9999	-0.46	38	38
IGF1R	0.009	0.042	-9999	-0.39	3	3
PI4KB	0.014	0	-9999	-10000	0	0
MFGE8	0.01	0.037	-9999	-0.35	3	3
SRC	0.012	0.026	-9999	-0.43	1	1
CDKN1B	-0.049	0.13	-9999	-0.43	17	17
VEGFA	0.001	0.064	-9999	-0.32	11	11
ILK	-0.049	0.13	-9999	-0.28	44	44
ROCK1	0.003	0.069	-9999	-0.43	7	7
AKT1	-0.04	0.12	-9999	-0.4	17	17
PTK2B	-0.024	0.11	-9999	-0.23	50	50
alphaV/beta3 Integrin/JAM-A	-0.083	0.17	-9999	-0.43	40	40
CBL	0.014	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.032	0.12	-9999	-0.27	45	45
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.003	0.084	-9999	-0.22	31	31
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.029	0.13	-9999	-0.36	21	21
alphaV/beta3 Integrin/Syndecan-1	-0.042	0.13	-9999	-0.28	53	53
PI4KA	0.012	0.019	-9999	-0.31	1	1
IGF-1R heterotetramer/IGF1/IRS1	-0.1	0.15	-9999	-0.42	39	39
PI4 Kinase	0.019	0.013	-9999	-0.2	1	1
PIK3CA	0.007	0.052	-9999	-0.43	4	4
alphaV/beta3 Integrin/Osteopontin	-0.072	0.16	-9999	-0.31	73	73
RPS6KB1	-0.073	0.16	-9999	-0.39	39	39
TLN1	0.014	0	-9999	-10000	0	0
MAPK3	-0.13	0.25	-9999	-0.5	77	77
GPR124	0.007	0.052	-9999	-0.43	4	4
MAPK1	-0.13	0.25	-9999	-0.5	77	77
PXN	0.014	0	-9999	-10000	0	0
PIK3R1	0.01	0.037	-9999	-0.43	2	2
alphaV/beta3 Integrin/Tumstatin	-0.066	0.14	-9999	-0.29	59	59
cell adhesion	-0.025	0.11	-9999	-0.26	45	45
ANGPTL3	0.006	0.007	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src	0.016	0.047	-9999	-0.17	16	16
IGF-1R heterotetramer	0.009	0.042	-9999	-0.39	3	3
Rac1/GDP	0.01	0	-9999	-10000	0	0
TGFBR2	0.012	0.019	-9999	-0.31	1	1
ITGB3	-0.068	0.17	-9999	-0.4	55	55
IGF1	-0.02	0.11	-9999	-0.4	23	23
RAC1	0.014	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.031	0.12	-9999	-0.27	48	48
apoptosis	0.003	0.069	-9999	-0.43	7	7
CD47	0.012	0.026	-9999	-0.43	1	1
alphaV/beta3 Integrin/CD47	-0.028	0.12	-9999	-0.27	46	46
VCL	0.014	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.077	0.16	-9999	-0.32	66	66
CSF1	0.002	0.067	-9999	-0.38	8	8
PIK3C2A	-0.064	0.18	-9999	-0.45	32	32
PI4 Kinase/Pyk2	-0.091	0.14	-9999	-0.37	41	41
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.025	0.11	-9999	-0.24	49	49
FAK1/Vinculin	-0.057	0.14	-9999	-0.36	37	37
alphaV beta3/Integrin/ppsTEM5	-0.031	0.12	-9999	-0.27	48	48
RHOA	0.014	0	-9999	-10000	0	0
VTN	-0.042	0.13	-9999	-0.34	45	45
BCAR1	0.009	0.045	-9999	-0.43	3	3
FGF2	-0.076	0.18	-9999	-0.42	59	59
F11R	-0.048	0.13	-9999	-0.29	61	61
alphaV/beta3 Integrin/Lactadherin	-0.03	0.12	-9999	-0.27	46	46
alphaV/beta3 Integrin/TGFBR2	-0.028	0.12	-9999	-0.27	45	45
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.02	0.058	-9999	-0.21	15	15
HSP90AA1	0.012	0.026	-9999	-0.43	1	1
alphaV/beta3 Integrin/Talin	-0.024	0.1	-9999	-0.24	45	45
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.012	0.1	-9999	-0.42	17	17
alphaV/beta3 Integrin/Pyk2	-0.021	0.11	-9999	-0.23	50	50
SDC1	-0.012	0.098	-9999	-0.37	19	19
VAV3	0	0.079	-9999	-0.37	4	4
PTPN11	0.014	0	-9999	-10000	0	0
IRS1	-0.006	0.091	-9999	-0.42	13	13
FAK1/Paxillin	-0.057	0.14	-9999	-0.36	37	37
cell migration	-0.047	0.13	-9999	-0.34	34	34
ITGAV	0.003	0.069	-9999	-0.43	7	7
PI3K	-0.072	0.17	-9999	-0.41	41	41
SPP1	-0.064	0.16	-9999	-0.39	54	54
KDR	0.009	0.042	-9999	-0.34	4	4
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.003	0.069	-9999	-0.43	7	7
COL4A3	-0.053	0.14	-9999	-0.35	51	51
angiogenesis	-0.13	0.25	-9999	-0.51	77	77
Rac1/GTP	0.007	0.073	-9999	-0.34	4	4
EDIL3	-0.075	0.16	-9999	-0.36	66	66
cell proliferation	-0.028	0.12	-9999	-0.27	45	45

×

Osteopontin-mediated 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.042	0.14	-9999	-0.39	24	24
NF kappa B1 p50/RelA/I kappa B alpha	-0.021	0.13	-9999	-0.39	19	19
alphaV/beta3 Integrin/Osteopontin/Src	-0.037	0.13	-9999	-0.28	58	58
AP1	-0.043	0.18	-9999	-0.47	27	27
ILK	-0.053	0.14	-9999	-0.38	27	27
bone resorption	-0.044	0.16	-9999	-0.42	28	28
PTK2B	0.01	0.037	-9999	-0.35	3	3
PYK2/p130Cas	-0.047	0.16	-9999	-0.4	29	29
ITGAV	0.005	0.069	-9999	-0.42	7	7
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.008	0.065	-9999	-0.32	10	10
alphaV/beta3 Integrin/Osteopontin	-0.062	0.16	-9999	-0.3	73	73
MAP3K1	-0.059	0.16	-9999	-0.28	76	76
JUN	0.013	0.002	-9999	-10000	0	0
MAPK3	-0.043	0.14	-9999	-0.39	24	24
MAPK1	-0.043	0.14	-9999	-0.39	24	24
Rac1/GDP	0.01	0	-9999	-10000	0	0
NFKB1	0.014	0	-9999	-10000	0	0
MAPK8	-0.054	0.16	-9999	-0.4	31	31
ITGB3	-0.065	0.17	-9999	-0.4	55	55
NFKBIA	-0.036	0.14	-9999	-0.41	21	21
FOS	0.005	0.05	-9999	-0.31	7	7
CD44	0.009	0.045	-9999	-0.43	3	3
CHUK	0.012	0.026	-9999	-0.43	1	1
PLAU	-0.044	0.2	-9999	-0.72	14	14
NF kappa B1 p50/RelA	-0.019	0.13	-9999	-0.37	21	21
BCAR1	0.009	0.045	-9999	-0.43	3	3
RELA	0.014	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.039	0.14	-9999	-0.29	57	57
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.066	0.16	-9999	-0.4	37	37
VAV3	-0.073	0.16	-9999	-0.39	42	42
MAP3K14	-0.052	0.15	-9999	-0.39	27	27
ROCK2	0.001	0.074	-9999	-0.43	8	8
SPP1	-0.062	0.16	-9999	-0.39	54	54
RAC1	0.014	0	-9999	-10000	0	0
Rac1/GTP	-0.061	0.15	-9999	-0.37	40	40
MMP2	-0.051	0.18	-9999	-0.46	34	34

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	-0.015	0.11	-10000	0	-0.41	19	19
positive regulation of NF-kappaB transcription factor activity	-0.031	0.11	-10000	0	-0.24	55	55
MAP2K4	0.002	0.083	-10000	0	-0.28	14	14
IKBKB	0.014	0	-10000	0	-10000	0	0
TNFRSF10B	-0.013	0.1	-10000	0	-0.43	17	17
TNFRSF10A	-0.044	0.14	-10000	0	-0.39	40	40
SMPD1	-0.007	0.069	-10000	0	-0.18	32	32
IKBKG	0.014	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	-0.032	0.12	-10000	0	-0.33	38	38
TRAIL/TRAILR2	-0.019	0.11	-10000	0	-0.3	35	35
TRAIL/TRAILR3	-0.034	0.12	-10000	0	-0.3	48	48
TRAIL/TRAILR1	-0.039	0.14	-10000	0	-0.31	51	51
TRAIL/TRAILR4	-0.031	0.11	-10000	0	-0.24	55	55
TRAIL/TRAILR1/DAP3/GTP	-0.02	0.11	-10000	0	-0.23	51	51
IKK complex	0.012	0.051	-10000	0	-0.32	1	1
RIPK1	0.014	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.01	0	-10000	0	-10000	0	0
MAPK3	-0.001	0.076	-10000	0	-0.28	19	19
MAP3K1	-0.004	0.087	-10000	0	-0.27	20	20
TRAILR4 (trimer)	-0.032	0.12	-10000	0	-0.32	38	38
TRADD	0.014	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	-0.044	0.14	-10000	0	-0.39	40	40
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.008	0.097	-10000	0	-0.24	37	37
CFLAR	0.012	0.026	-10000	0	-0.43	1	1
MAPK1	-0.001	0.076	-10000	0	-0.28	19	19
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.005	0.1	-10000	0	-0.23	38	38
mol:ceramide	-0.007	0.069	-10000	0	-0.18	32	32
FADD	0.012	0.019	-10000	0	-0.31	1	1
MAPK8	0.004	0.085	-10000	0	-0.3	12	12
TRAF2	0.014	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	-0.035	0.13	-10000	0	-0.39	34	34
CHUK	0.012	0.026	-10000	0	-0.43	1	1
TRAIL/TRAILR1/FADD	-0.024	0.12	-10000	0	-0.25	52	52
DAP3	0.014	0	-10000	0	-10000	0	0
CASP10	-0.015	0.12	0.23	3	-0.34	22	25
JNK cascade	-0.031	0.11	-10000	0	-0.24	55	55
TRAIL (trimer)	-0.015	0.11	-10000	0	-0.41	19	19
TNFRSF10C	-0.035	0.13	-10000	0	-0.39	34	34
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.012	0.1	-10000	0	-0.24	38	38
TRAIL/TRAILR2/FADD	-0.006	0.091	-10000	0	-0.24	36	36
cell death	-0.007	0.068	-10000	0	-0.18	32	32
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.005	0.076	-10000	0	-0.2	32	32
TRAILR2 (trimer)	-0.013	0.1	-10000	0	-0.43	17	17
CASP8	0.002	0.055	-10000	0	-0.82	1	1
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.011	0.079	-10000	0	-0.2	32	32

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	0.021	0.12	0.41	23	-10000	0	23
PI3K Class IB/PDE3B	-0.021	0.12	-10000	0	-0.41	23	23
PDE3B	-0.021	0.12	-10000	0	-0.41	23	23

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.032	0.14	-9999	-0.3	48	48
MAP4K1	-0.024	0.12	-9999	-0.4	25	25
MAP3K8	-0.004	0.08	-9999	-0.36	13	13
PRKCB	-0.049	0.15	-9999	-0.38	44	44
DBNL	0.014	0	-9999	-10000	0	0
CRKL	0.012	0.019	-9999	-0.31	1	1
MAP3K1	-0.02	0.12	-9999	-0.41	18	18
JUN	-0.053	0.22	-9999	-0.66	31	31
MAP3K7	-0.017	0.12	-9999	-0.42	16	16
GRAP2	-0.011	0.098	-9999	-0.39	17	17
CRK	0.014	0	-9999	-10000	0	0
MAP2K4	-0.017	0.13	-9999	-0.4	21	21
LAT	-0.021	0.11	-9999	-0.36	26	26
LCP2	-0.015	0.11	-9999	-0.43	18	18
MAPK8	-0.062	0.23	-9999	-0.7	31	31
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.021	0.13	-9999	-0.33	30	30
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.023	0.13	-9999	-0.28	48	48

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	-0.005	0.084	-10000	0	-0.38	13	13
GNB1/GNG2	-0.044	0.072	-10000	0	-0.19	51	51
AKT1	-0.01	0.098	-10000	0	-0.2	51	51
EGF	-0.097	0.18	-10000	0	-0.4	76	76
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.007	0.076	-10000	0	-0.34	5	5
mol:Ca2+	-0.03	0.14	-10000	0	-0.3	54	54
LYN	0.015	0.064	-10000	0	-0.4	2	2
RhoA/GTP	-0.026	0.049	-10000	0	-0.12	51	51
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.039	0.16	-10000	0	-0.35	53	53
GNG2	-0.004	0.086	-10000	0	-0.43	11	11
ARRB2	0.014	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.001	0.086	-10000	0	-0.37	12	12
G beta5/gamma2	-0.057	0.096	-10000	0	-0.25	51	51
PRKCH	-0.037	0.16	-10000	0	-0.35	52	52
DNM1	-0.002	0.076	-10000	0	-0.37	11	11
TXA2/TP beta/beta Arrestin3	-0.007	0.03	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	-0.007	0.088	-10000	0	-0.37	15	15
G12 family/GTP	-0.066	0.12	-10000	0	-0.3	52	52
ADRBK1	0.012	0.026	-10000	0	-0.43	1	1
ADRBK2	0.004	0.064	-10000	0	-0.43	6	6
RhoA/GTP/ROCK1	0.012	0.041	-10000	0	-0.25	7	7
mol:GDP	0.019	0.11	0.32	16	-10000	0	16
mol:NADP	0.001	0.067	-10000	0	-0.36	9	9
RAB11A	0.014	0	-10000	0	-10000	0	0
PRKG1	-0.017	0.1	-10000	0	-0.37	22	22
mol:IP3	-0.043	0.17	-10000	0	-0.38	54	54
cell morphogenesis	0.011	0.041	-10000	0	-0.25	7	7
PLCB2	-0.069	0.23	-10000	0	-0.51	54	54
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.026	0.092	-10000	0	-0.32	10	10
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.008	0.078	-10000	0	-0.34	7	7
RHOA	0.014	0	-10000	0	-10000	0	0
PTGIR	0.009	0.045	-10000	0	-0.43	3	3
PRKCB1	-0.043	0.17	-10000	0	-0.37	52	52
GNAQ	0.014	0	-10000	0	-10000	0	0
mol:L-citrulline	0.001	0.067	-10000	0	-0.36	9	9
TXA2/TXA2-R family	-0.069	0.23	-10000	0	-0.53	52	52
LCK	-0.021	0.1	-10000	0	-0.32	14	14
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.006	0.059	-10000	0	-0.32	2	2
TXA2-R family/G12 family/GDP/G beta/gamma	0.018	0.034	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.013	0.059	-10000	0	-0.31	2	2
MAPK14	-0.017	0.11	-10000	0	-0.23	52	52
TGM2/GTP	-0.052	0.2	-10000	0	-0.43	55	55
MAPK11	-0.019	0.12	-10000	0	-0.24	52	52
ARHGEF1	-0.01	0.085	-10000	0	-0.17	52	52
GNAI2	0.014	0	-10000	0	-10000	0	0
JNK cascade	-0.044	0.18	-10000	0	-0.38	52	52
RAB11/GDP	0.014	0.001	-10000	0	-10000	0	0
ICAM1	-0.028	0.14	-10000	0	-0.29	51	51
cAMP biosynthetic process	-0.043	0.16	-10000	0	-0.35	55	55
Gq family/GTP/EBP50	0.005	0.053	-10000	0	-0.22	10	10
actin cytoskeleton reorganization	0.011	0.041	-10000	0	-0.25	7	7
SRC	0.015	0.061	-10000	0	-0.32	3	3
GNB5	0.009	0.045	-10000	0	-0.43	3	3
GNB1	0.014	0	-10000	0	-10000	0	0
EGF/EGFR	-0.038	0.1	-10000	0	-0.31	22	22
VCAM1	-0.036	0.15	-10000	0	-0.32	52	52
TP beta/Gq family/GDP/G beta5/gamma2	0.001	0.086	-10000	0	-0.37	12	12
platelet activation	-0.022	0.15	-10000	0	-0.3	53	53
PGI2/IP	0.007	0.032	-10000	0	-0.3	3	3
PRKACA	0.007	0.048	-10000	0	-0.22	11	11
Gq family/GDP/G beta5/gamma2	0.002	0.08	-10000	0	-0.33	12	12
TXA2/TP beta/beta Arrestin2	-0.014	0.066	-10000	0	-0.45	6	6
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.001	0.066	-10000	0	-0.22	19	19
mol:DAG	-0.05	0.19	-10000	0	-0.42	52	52
EGFR	-0.028	0.12	-10000	0	-0.34	33	33
TXA2/TP alpha	-0.063	0.22	-10000	0	-0.48	55	55
Gq family/GTP	-0.014	0.046	-10000	0	-0.19	13	13
YES1	0.012	0.064	-10000	0	-0.3	3	3
GNAI2/GTP	-0.019	0.055	-10000	0	-0.38	2	2
PGD2/DP	-0.005	0.061	-10000	0	-0.26	15	15
SLC9A3R1	0.011	0.032	-10000	0	-0.37	2	2
FYN	0.015	0.059	-10000	0	-0.32	2	2
mol:NO	0.001	0.067	-10000	0	-0.36	9	9
GNA15	-0.006	0.086	-10000	0	-0.38	14	14
PGK/cGMP	-0.006	0.076	-10000	0	-0.22	29	29
RhoA/GDP	0.014	0.001	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0.006	0.086	-10000	0	-0.36	6	6
NOS3	0.001	0.067	-10000	0	-0.36	9	9
RAC1	0.014	0	-10000	0	-10000	0	0
PRKCA	-0.041	0.16	-10000	0	-0.35	52	52
PRKCB	-0.051	0.17	-10000	0	-0.37	55	55
PRKCE	-0.034	0.16	-10000	0	-0.35	51	51
PRKCD	-0.04	0.17	-10000	0	-0.38	51	51
PRKCG	-0.045	0.17	-10000	0	-0.38	52	52
muscle contraction	-0.064	0.22	-10000	0	-0.49	52	52
PRKCZ	-0.037	0.16	-10000	0	-0.34	52	52
ARR3	0	0.026	-10000	0	-0.31	2	2
TXA2/TP beta	0.008	0.072	-10000	0	-0.42	2	2
PRKCQ	-0.055	0.18	-10000	0	-0.39	53	53
MAPKKK cascade	-0.06	0.21	-10000	0	-0.46	54	54
SELE	-0.042	0.16	-10000	0	-0.34	52	52
TP beta/GNAI2/GDP/G beta/gamma	0.014	0.071	-10000	0	-0.3	3	3
ROCK1	0.003	0.069	-10000	0	-0.43	7	7
GNA14	-0.027	0.11	-10000	0	-0.32	34	34
chemotaxis	-0.081	0.26	-10000	0	-0.6	51	51
GNA12	0.014	0	-10000	0	-10000	0	0
GNA13	0.014	0	-10000	0	-10000	0	0
GNA11	0.012	0.026	-10000	0	-0.43	1	1
Rac1/GTP	0.01	0.001	-10000	0	-10000	0	0

×

Syndecan-2-mediated signaling 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
Syndecan-2/Fibronectin	-0.013	0.09	-9999	-0.22	41	41
EPHB2	-0.012	0.1	-9999	-0.42	17	17
Syndecan-2/TACI	-0.046	0.11	-9999	-0.2	83	83
LAMA1	-0.079	0.17	-9999	-0.39	65	65
Syndecan-2/alpha2 ITGB1	-0.015	0.1	-9999	-0.23	37	37
HRAS	0.014	0	-9999	-10000	0	0
Syndecan-2/CASK	-0.007	0.064	-9999	-0.2	26	26
ITGA5	0.003	0.062	-9999	-0.35	8	8
BAX	0.011	0.063	-9999	-10000	0	0
EPB41	0.01	0.037	-9999	-0.43	2	2
positive regulation of cell-cell adhesion	0	0.063	-9999	-0.18	29	29
LAMA3	-0.02	0.11	-9999	-0.35	26	26
EZR	0.007	0.052	-9999	-0.43	4	4
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	0.012	0.026	-9999	-0.43	1	1
Syndecan-2/MMP2	-0.022	0.1	-9999	-0.22	51	51
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.004	0.086	-9999	-0.29	22	22
dendrite morphogenesis	-0.013	0.092	-9999	-0.23	40	40
Syndecan-2/GM-CSF	-0.007	0.073	-9999	-0.2	35	35
determination of left/right symmetry	-0.007	0.078	-9999	-0.25	26	26
Syndecan-2/PKC delta	0.002	0.065	-9999	-0.2	26	26
GNB2L1	0.014	0	-9999	-10000	0	0
MAPK3	0	0.065	-9999	-0.22	14	14
MAPK1	0	0.065	-9999	-0.22	14	14
Syndecan-2/RACK1	0.011	0.056	-9999	-0.2	13	13
NF1	0.007	0.052	-9999	-0.43	4	4
FGFR/FGF/Syndecan-2	-0.007	0.078	-9999	-0.25	26	26
ITGA2	-0.018	0.11	-9999	-0.4	22	22
MAPK8	0.003	0.071	-9999	-0.24	17	17
Syndecan-2/alpha2/beta1 Integrin	-0.045	0.13	-9999	-0.25	64	64
Syndecan-2/Kininogen	-0.007	0.067	-9999	-0.2	30	30
ITGB1	0.011	0.032	-9999	-0.37	2	2
SRC	0.013	0.054	-9999	-0.18	14	14
Syndecan-2/CASK/Protein 4.1	0.001	0.062	-9999	-0.18	28	28
extracellular matrix organization	-0.002	0.082	-9999	-0.23	27	27
actin cytoskeleton reorganization	-0.013	0.09	-9999	-0.22	41	41
Syndecan-2/Caveolin-2/Ras	0.01	0.061	-9999	-0.21	14	14
Syndecan-2/Laminin alpha3	-0.017	0.091	-9999	-0.2	49	49
Syndecan-2/RasGAP	0.015	0.058	-9999	-0.18	16	16
alpha5/beta1 Integrin	0.011	0.051	-9999	-0.26	9	9
PRKCD	0.014	0	-9999	-10000	0	0
Syndecan-2 dimer	-0.013	0.092	-9999	-0.23	40	40
GO:0007205	0.003	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.019	0.057	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
SDCBP	0.009	0.045	-9999	-0.43	3	3
TNFRSF13B	-0.069	0.16	-9999	-0.36	61	61
RASA1	0.009	0.045	-9999	-0.43	3	3
alpha2/beta1 Integrin	-0.004	0.086	-9999	-0.29	22	22
Syndecan-2/Synbindin	0.002	0.065	-9999	-0.2	26	26
TGFB1	0.006	0.058	-9999	-0.43	5	5
CASP3	0.008	0.059	-9999	-0.21	13	13
FN1	-0.012	0.1	-9999	-0.42	17	17
Syndecan-2/IL8	-0.028	0.1	-9999	-0.21	62	62
SDC2	-0.007	0.078	-9999	-0.25	26	26
KNG1	0	0.037	-9999	-0.31	4	4
Syndecan-2/Neurofibromin	-0.001	0.071	-9999	-0.2	30	30
TRAPPC4	0.014	0	-9999	-10000	0	0
CSF2	-0.002	0.059	-9999	-0.31	10	10
Syndecan-2/TGFB1	-0.002	0.083	-9999	-0.24	27	27
Syndecan-2/Syntenin/PI-4-5-P2	0	0.063	-9999	-0.18	29	29
Syndecan-2/Ezrin	0.008	0.065	-9999	-0.21	17	17
PRKACA	0.005	0.064	-9999	-0.21	17	17
angiogenesis	-0.028	0.1	-9999	-0.21	62	62
MMP2	-0.028	0.12	-9999	-0.38	30	30
IL8	-0.039	0.13	-9999	-0.36	39	39
calcineurin-NFAT signaling pathway	-0.046	0.11	-9999	-0.2	83	83

×

IL27-mediated signaling events

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
TGFB1	0.005	0.059	-10000	0	-0.43	5	5
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.081	0.21	0.61	26	-10000	0	26
IL27/IL27R/JAK1	-0.088	0.25	-10000	0	-0.86	19	19
TBX21	-0.12	0.23	-10000	0	-0.51	54	54
IL12B	0	0.05	-10000	0	-0.31	7	7
IL12A	-0.022	0.087	-10000	0	-0.27	29	29
IL6ST	-0.023	0.12	-10000	0	-0.44	20	20
IL27RA/JAK1	-0.046	0.24	-10000	0	-1.1	12	12
IL27	-0.011	0.082	-10000	0	-0.36	14	14
TYK2	0.009	0.01	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.008	0.072	-10000	0	-0.57	1	1
T-helper 2 cell differentiation	0.081	0.21	0.61	26	-10000	0	26
T cell proliferation during immune response	0.081	0.21	0.61	26	-10000	0	26
MAPKKK cascade	-0.081	0.21	-10000	0	-0.61	26	26
STAT3	0.014	0	-10000	0	-10000	0	0
STAT2	0.014	0	-10000	0	-10000	0	0
STAT1	0.011	0.026	-10000	0	-0.42	1	1
IL12RB1	-0.043	0.14	-10000	0	-0.4	38	38
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.14	0.24	-10000	0	-0.47	77	77
IL27/IL27R/JAK2/TYK2	-0.082	0.21	-10000	0	-0.62	26	26
positive regulation of T cell mediated cytotoxicity	-0.081	0.21	-10000	0	-0.61	26	26
STAT1 (dimer)	-0.15	0.27	0.41	5	-0.75	31	36
JAK2	0.001	0.067	-10000	0	-0.42	7	7
JAK1	0.013	0.003	-10000	0	-10000	0	0
STAT2 (dimer)	-0.073	0.2	-10000	0	-0.58	26	26
T cell proliferation	-0.087	0.21	-10000	0	-0.58	30	30
IL12/IL12R/TYK2/JAK2	-0.066	0.15	-10000	0	-0.46	17	17
IL17A	-0.008	0.072	-10000	0	-0.57	1	1
mast cell activation	0.081	0.21	0.61	26	-10000	0	26
IFNG	-0.025	0.05	-10000	0	-0.12	54	54
T cell differentiation	-0.007	0.009	-10000	0	-0.021	72	72
STAT3 (dimer)	-0.073	0.2	-10000	0	-0.58	26	26
STAT5A (dimer)	-0.074	0.2	-10000	0	-0.58	26	26
STAT4 (dimer)	-0.093	0.22	-10000	0	-0.57	34	34
STAT4	-0.033	0.13	-10000	0	-0.38	34	34
T cell activation	-0.002	0.027	0.11	14	-10000	0	14
IL27R/JAK2/TYK2	-0.062	0.24	-10000	0	-0.84	19	19
GATA3	-0.15	0.42	-10000	0	-1.2	38	38
IL18	-0.021	0.088	-10000	0	-0.28	29	29
positive regulation of mast cell cytokine production	-0.071	0.19	-10000	0	-0.57	26	26
IL27/EBI3	-0.032	0.11	-10000	0	-0.29	41	41
IL27RA	-0.053	0.25	-10000	0	-1.2	12	12
IL6	-0.019	0.1	-10000	0	-0.35	25	25
STAT5A	0.012	0.026	-10000	0	-0.43	1	1
monocyte differentiation	-0.001	0.003	-10000	0	-10000	0	0
IL2	0.019	0.1	0.48	12	-10000	0	12
IL1B	-0.034	0.1	-10000	0	-0.26	45	45
EBI3	-0.035	0.13	-10000	0	-0.4	31	31
TNF	-0.015	0.079	-10000	0	-0.27	25	25

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.009	0.11	-9999	-0.46	15	15
Syndecan-4/Syndesmos	-0.038	0.15	-9999	-0.43	33	33
positive regulation of JNK cascade	-0.048	0.16	-9999	-0.44	35	35
Syndecan-4/ADAM12	-0.043	0.16	-9999	-0.45	34	34
CCL5	-0.059	0.15	-9999	-0.38	52	52
Rac1/GDP	0.01	0	-9999	-10000	0	0
DNM2	0.014	0	-9999	-10000	0	0
ITGA5	0.003	0.062	-9999	-0.35	8	8
SDCBP	0.009	0.045	-9999	-0.43	3	3
PLG	0	0.027	-9999	-0.31	2	2
ADAM12	0.002	0.067	-9999	-0.38	8	8
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	-0.008	0.021	-9999	-0.12	1	1
Syndecan-4/Laminin alpha1	-0.08	0.18	-9999	-0.47	37	37
Syndecan-4/CXCL12/CXCR4	-0.051	0.17	-9999	-0.47	35	35
Syndecan-4/Laminin alpha3	-0.053	0.16	-9999	-0.44	34	34
MDK	-0.028	0.12	-9999	-0.39	29	29
Syndecan-4/FZD7	-0.046	0.16	-9999	-0.44	36	36
Syndecan-4/Midkine	-0.057	0.17	-9999	-0.46	36	36
FZD7	-0.004	0.082	-9999	-0.37	13	13
Syndecan-4/FGFR1/FGF	-0.078	0.17	-9999	-0.44	39	39
THBS1	-0.015	0.1	-9999	-0.39	20	20
integrin-mediated signaling pathway	-0.055	0.17	-9999	-0.46	37	37
positive regulation of MAPKKK cascade	-0.048	0.16	-9999	-0.44	35	35
Syndecan-4/TACI	-0.075	0.17	-9999	-0.46	38	38
CXCR4	-0.004	0.082	-9999	-0.39	12	12
cell adhesion	-0.002	0.08	-9999	-0.24	24	24
Syndecan-4/Dynamin	-0.038	0.15	-9999	-0.43	33	33
Syndecan-4/TSP1	-0.051	0.17	-9999	-0.45	37	37
Syndecan-4/GIPC	-0.038	0.15	-9999	-0.43	33	33
Syndecan-4/RANTES	-0.07	0.18	-9999	-0.5	34	34
ITGB1	0.011	0.032	-9999	-0.37	2	2
LAMA1	-0.079	0.17	-9999	-0.39	65	65
LAMA3	-0.02	0.11	-9999	-0.35	26	26
RAC1	0.014	0	-9999	-10000	0	0
PRKCA	0.003	0.085	-9999	-0.37	12	12
Syndecan-4/alpha-Actinin	-0.041	0.16	-9999	-0.44	33	33
TFPI	-0.001	0.072	-9999	-0.35	11	11
F2	-0.004	0.037	-9999	-0.3	4	4
alpha5/beta1 Integrin	0.011	0.051	-9999	-0.26	9	9
positive regulation of cell adhesion	-0.087	0.18	-9999	-0.44	43	43
ACTN1	0.007	0.052	-9999	-0.43	4	4
TNC	-0.028	0.13	-9999	-0.42	27	27
Syndecan-4/CXCL12	-0.052	0.17	-9999	-0.47	33	33
FGF6	0	0.002	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
CXCL12	-0.017	0.11	-9999	-0.41	20	20
TNFRSF13B	-0.069	0.16	-9999	-0.36	61	61
FGF2	-0.076	0.18	-9999	-0.42	59	59
FGFR1	-0.006	0.082	-9999	-0.35	15	15
Syndecan-4/PI-4-5-P2	-0.046	0.15	-9999	-0.44	33	33
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.01	0.099	-9999	-0.4	17	17
cell migration	-0.003	0.009	-9999	-10000	0	0
PRKCD	0.015	0.006	-9999	-10000	0	0
vasculogenesis	-0.049	0.16	-9999	-0.44	37	37
SDC4	-0.048	0.16	-9999	-0.46	33	33
Syndecan-4/Tenascin C	-0.057	0.18	-9999	-0.47	37	37
Syndecan-4/PI-4-5-P2/PKC alpha	-0.007	0.017	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.04	0.15	-9999	-0.43	33	33
MMP9	-0.067	0.16	-9999	-0.37	59	59
Rac1/GTP	-0.002	0.082	-9999	-0.24	24	24
cytoskeleton organization	-0.037	0.15	-9999	-0.42	33	33
GIPC1	0.014	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.045	0.16	-9999	-0.44	33	33

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.12	0.36	-9999	-0.86	31	31
HDAC7	0.013	0.026	-9999	-0.43	1	1
HIF1A/ARNT/Cbp/p300/Src-1	-0.084	0.32	-9999	-0.78	21	21
SMAD4	0.015	0	-9999	-10000	0	0
ID2	-0.12	0.36	-9999	-0.86	31	31
AP1	0.015	0.035	-9999	-0.2	7	7
ABCG2	-0.13	0.37	-9999	-0.88	33	33
HIF1A	-0.01	0.073	-9999	-0.56	1	1
TFF3	-0.17	0.39	-9999	-0.9	40	40
GATA2	-0.004	0.083	-9999	-0.38	13	13
AKT1	-0.015	0.075	-9999	-0.22	4	4
response to hypoxia	-0.03	0.077	-9999	-0.19	14	14
MCL1	-0.12	0.36	-9999	-0.86	31	31
NDRG1	-0.13	0.37	-9999	-0.89	32	32
SERPINE1	-0.13	0.38	-9999	-0.91	33	33
FECH	-0.12	0.36	-9999	-0.86	31	31
FURIN	-0.12	0.36	-9999	-0.86	31	31
NCOA2	0	0.076	-9999	-0.42	9	9
EP300	-0.012	0.11	-9999	-0.31	10	10
HMOX1	-0.12	0.37	-9999	-0.88	32	32
BHLHE40	-0.12	0.36	-9999	-0.86	33	33
BHLHE41	-0.13	0.37	-9999	-0.89	33	33
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.021	0.093	-9999	-0.3	3	3
ENG	0.024	0.084	-9999	-0.32	1	1
JUN	0.014	0.004	-9999	-10000	0	0
RORA	-0.12	0.37	-9999	-0.88	32	32
ABCB1	-0.085	0.24	-9999	-1.1	13	13
TFRC	-0.12	0.36	-9999	-0.86	32	32
CXCR4	-0.13	0.37	-9999	-0.88	32	32
TF	-0.2	0.4	-9999	-0.88	46	46
CITED2	-0.12	0.36	-9999	-0.87	31	31
HIF1A/ARNT	-0.12	0.43	-9999	-0.98	31	31
LDHA	-0.026	0.082	-9999	-1.2	1	1
ETS1	-0.12	0.36	-9999	-0.86	31	31
PGK1	-0.12	0.36	-9999	-0.86	31	31
NOS2	-0.14	0.38	-9999	-0.86	34	34
ITGB2	-0.13	0.38	-9999	-0.89	34	34
ALDOA	-0.12	0.36	-9999	-0.86	31	31
Cbp/p300/CITED2	-0.13	0.38	-9999	-0.93	29	29
FOS	0.006	0.05	-9999	-0.3	7	7
HK2	-0.12	0.37	-9999	-0.88	31	31
SP1	0.018	0.016	-9999	-10000	0	0
GCK	-0.063	0.29	-9999	-1.2	12	12
HK1	-0.12	0.36	-9999	-0.86	31	31
NPM1	-0.12	0.36	-9999	-0.86	31	31
EGLN1	-0.12	0.36	-9999	-0.86	31	31
CREB1	0.02	0.001	-9999	-10000	0	0
PGM1	-0.12	0.36	-9999	-0.87	32	32
SMAD3	0.011	0.037	-9999	-0.43	2	2
EDN1	-0.029	0.22	-9999	-1	9	9
IGFBP1	-0.14	0.36	-9999	-0.88	32	32
VEGFA	-0.068	0.29	-9999	-0.71	22	22
HIF1A/JAB1	-0.001	0.045	-9999	-0.4	1	1
CP	-0.16	0.39	-9999	-0.88	40	40
CXCL12	-0.13	0.38	-9999	-0.86	39	39
COPS5	0.014	0.002	-9999	-10000	0	0
SMAD3/SMAD4	0.02	0.026	-9999	-0.29	2	2
BNIP3	-0.12	0.36	-9999	-0.86	31	31
EGLN3	-0.13	0.37	-9999	-0.9	31	31
CA9	-0.16	0.39	-9999	-0.91	37	37
TERT	-0.14	0.38	-9999	-0.86	37	37
ENO1	-0.12	0.36	-9999	-0.86	31	31
PFKL	-0.12	0.36	-9999	-0.86	31	31
NCOA1	0.014	0.001	-9999	-10000	0	0
ADM	-0.13	0.38	-9999	-0.87	36	36
ARNT	-0.008	0.065	-9999	-10000	0	0
HNF4A	-0.007	0.058	-9999	-0.32	8	8
ADFP	-0.14	0.35	-9999	-0.86	32	32
SLC2A1	-0.065	0.29	-9999	-0.68	22	22
LEP	-0.14	0.37	-9999	-0.86	34	34
HIF1A/ARNT/Cbp/p300	-0.092	0.33	-9999	-0.8	22	22
EPO	-0.052	0.26	-9999	-0.71	13	13
CREBBP	-0.012	0.11	-9999	-0.31	10	10
HIF1A/ARNT/Cbp/p300/HDAC7	-0.079	0.32	-9999	-0.79	22	22
PFKFB3	-0.12	0.36	-9999	-0.86	31	31
NT5E	-0.15	0.39	-9999	-0.9	37	37

×

amb2 Integrin 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
alphaM/beta2 Integrin/proMMP-2	-0.025	0.14	-9999	-0.37	33	33
alphaM/beta2 Integrin/GPIbA	-0.032	0.13	-9999	-0.31	36	36
alphaM/beta2 Integrin/proMMP-9	-0.048	0.15	-9999	-0.32	51	51
PLAUR	-0.002	0.076	-9999	-0.36	12	12
HMGB1	0.01	0.014	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.002	0.1	-9999	-0.37	18	18
AGER	0.005	0.044	-9999	-0.34	4	4
RAP1A	0.014	0	-9999	-10000	0	0
SELPLG	-0.002	0.08	-9999	-0.42	10	10
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.003	0.12	-9999	-0.37	21	21
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.068	0.16	-9999	-0.38	59	59
CYR61	-0.003	0.074	-9999	-0.33	13	13
TLN1	0.014	0	-9999	-10000	0	0
Rap1/GTP	-0.05	0.091	-9999	-0.32	18	18
RHOA	0.014	0	-9999	-10000	0	0
P-selectin oligomer	-0.074	0.17	-9999	-0.38	62	62
MYH2	-0.046	0.11	-9999	-0.31	23	23
MST1R	-0.07	0.15	-9999	-0.34	66	66
leukocyte activation during inflammatory response	-0.016	0.097	-9999	-0.34	18	18
APOB	-0.012	0.073	-9999	-0.31	16	16
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.028	0.12	-9999	-0.38	30	30
JAM3	-0.011	0.1	-9999	-0.42	16	16
GP1BA	-0.038	0.12	-9999	-0.33	42	42
alphaM/beta2 Integrin/CTGF	-0.016	0.13	-9999	-0.36	26	26
alphaM/beta2 Integrin	-0.047	0.12	-9999	-0.31	29	29
JAM3 homodimer	-0.011	0.1	-9999	-0.42	16	16
ICAM2	0.01	0.037	-9999	-0.35	3	3
ICAM1	0.003	0.069	-9999	-0.43	7	7
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.047	0.12	-9999	-0.31	29	29
cell adhesion	-0.032	0.13	-9999	-0.3	36	36
NFKB1	-0.011	0.16	-9999	-0.4	29	29
THY1	0.008	0.046	-9999	-0.37	4	4
RhoA/GDP	0.01	0	-9999	-10000	0	0
Lipoprotein(a)	-0.006	0.045	-9999	-0.18	17	17
alphaM/beta2 Integrin/LRP/tPA	-0.001	0.11	-9999	-0.34	23	23
IL6	-0.021	0.18	-9999	-0.56	20	20
ITGB2	-0.014	0.1	-9999	-0.42	16	16
elevation of cytosolic calcium ion concentration	-0.009	0.13	-9999	-0.38	25	25
alphaM/beta2 Integrin/JAM2/JAM3	-0.009	0.12	-9999	-0.31	32	32
JAM2	0.004	0.059	-9999	-0.36	7	7
alphaM/beta2 Integrin/ICAM1	-0.035	0.14	-9999	-0.3	40	40
alphaM/beta2 Integrin/uPA/Plg	-0.01	0.12	-9999	-0.39	20	20
RhoA/GTP	-0.048	0.12	-9999	-0.27	38	38
positive regulation of phagocytosis	-0.031	0.14	-9999	-0.51	18	18
Ron/MSP	-0.041	0.12	-9999	-0.24	67	67
alphaM/beta2 Integrin/uPAR/uPA	-0.009	0.13	-9999	-0.39	25	25
alphaM/beta2 Integrin/uPAR	-0.011	0.12	-9999	-0.34	25	25
PLAU	-0.005	0.082	-9999	-0.36	14	14
PLAT	-0.004	0.082	-9999	-0.37	13	13
actin filament polymerization	-0.044	0.11	-9999	-0.3	23	23
MST1	0.009	0.045	-9999	-0.43	3	3
alphaM/beta2 Integrin/lipoprotein(a)	-0.014	0.098	-9999	-0.34	18	18
TNF	-0.026	0.21	-9999	-0.66	21	21
RAP1B	0.012	0.019	-9999	-0.31	1	1
alphaM/beta2 Integrin/uPA	-0.012	0.13	-9999	-0.4	23	23
fibrinolysis	-0.011	0.12	-9999	-0.39	20	20
HCK	-0.004	0.086	-9999	-0.43	11	11
dendritic cell antigen processing and presentation	-0.047	0.12	-9999	-0.31	29	29
VTN	-0.042	0.13	-9999	-0.34	45	45
alphaM/beta2 Integrin/CYR61	-0.011	0.11	-9999	-0.34	25	25
LPA	-0.001	0.026	-9999	-0.31	2	2
LRP1	0.014	0	-9999	-10000	0	0
cell migration	-0.058	0.17	-9999	-0.36	53	53
FN1	-0.012	0.1	-9999	-0.42	17	17
alphaM/beta2 Integrin/Thy1	-0.005	0.11	-9999	-0.36	20	20
MPO	-0.015	0.1	-9999	-0.39	20	20
KNG1	0	0.037	-9999	-0.31	4	4
RAP1/GDP	0.018	0.011	-9999	-0.16	1	1
ROCK1	-0.045	0.12	-9999	-0.31	23	23
ELA2	0	0	-9999	-10000	0	0
PLG	-0.001	0.026	-9999	-0.31	2	2
CTGF	-0.012	0.096	-9999	-0.36	19	19
alphaM/beta2 Integrin/Hck	-0.011	0.14	-9999	-0.48	19	19
ITGAM	-0.008	0.091	-9999	-0.43	12	12
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.046	0.16	-9999	-0.3	57	57
HP	-0.071	0.15	-9999	-0.35	63	63
leukocyte adhesion	-0.01	0.14	-9999	-0.47	15	15
SELP	-0.074	0.17	-9999	-0.39	62	62

×

EPHB forward signaling

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
Ephrin A5/EPHB2	-0.023	0.097	-10000	0	-0.25	44	44
cell-cell adhesion	0.062	0.091	0.29	22	-10000	0	22
Ephrin B/EPHB2/RasGAP	-0.02	0.1	-10000	0	-0.2	56	56
ITSN1	0.014	0	-10000	0	-10000	0	0
PIK3CA	0.007	0.052	-10000	0	-0.43	4	4
SHC1	0.014	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.002	0.069	-10000	0	-0.23	23	23
Ephrin B1/EPHB1	-0.013	0.076	-10000	0	-0.19	42	42
HRAS/GDP	-0.052	0.091	-10000	0	-0.29	17	17
Ephrin B/EPHB1/GRB7	-0.05	0.12	-10000	0	-0.23	60	60
Endophilin/SYNJ1	-0.022	0.09	-10000	0	-0.19	53	53
KRAS	0.012	0.019	-10000	0	-0.31	1	1
Ephrin B/EPHB1/Src	-0.031	0.11	-10000	0	-0.21	54	54
endothelial cell migration	0.009	0.064	-10000	0	-0.21	18	18
GRB2	0.014	0	-10000	0	-10000	0	0
GRB7	-0.027	0.1	-10000	0	-0.31	33	33
PAK1	-0.025	0.098	-10000	0	-0.29	8	8
HRAS	0.014	0	-10000	0	-10000	0	0
RRAS	-0.023	0.092	-10000	0	-0.19	54	54
DNM1	-0.002	0.076	-10000	0	-0.37	11	11
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.034	0.097	-10000	0	-0.2	53	53
lamellipodium assembly	-0.062	0.091	-10000	0	-0.29	22	22
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.018	0.085	-10000	0	-0.22	16	16
PIK3R1	0.01	0.037	-10000	0	-0.43	2	2
EPHB2	-0.012	0.1	-10000	0	-0.42	17	17
EPHB3	-0.019	0.11	-10000	0	-0.41	22	22
EPHB1	-0.039	0.13	-10000	0	-0.34	41	41
EPHB4	-0.007	0.093	-10000	0	-0.43	13	13
mol:GDP	-0.033	0.11	-10000	0	-0.25	43	43
Ephrin B/EPHB2	-0.025	0.099	-10000	0	-0.21	53	53
Ephrin B/EPHB3	-0.028	0.1	-10000	0	-0.22	54	54
JNK cascade	-0.007	0.084	-10000	0	-0.22	27	27
Ephrin B/EPHB1	-0.037	0.1	-10000	0	-0.22	53	53
RAP1/GDP	-0.018	0.1	-10000	0	-0.3	13	13
EFNB2	0.003	0.056	-10000	0	-0.31	9	9
EFNB3	-0.06	0.16	-10000	0	-0.4	51	51
EFNB1	0.012	0.019	-10000	0	-0.31	1	1
Ephrin B2/EPHB1-2	-0.021	0.097	-10000	0	-0.25	30	30
RAP1B	0.012	0.019	-10000	0	-0.31	1	1
RAP1A	0.014	0	-10000	0	-10000	0	0
CDC42/GTP	-0.061	0.092	-10000	0	-0.36	9	9
Rap1/GTP	-0.054	0.079	-10000	0	-0.31	9	9
axon guidance	-0.023	0.097	-10000	0	-0.24	44	44
MAPK3	-0.006	0.076	-10000	0	-0.25	4	4
MAPK1	-0.006	0.076	-10000	0	-0.25	4	4
Rac1/GDP	-0.024	0.1	-10000	0	-0.23	41	41
actin cytoskeleton reorganization	-0.048	0.075	-10000	0	-0.27	17	17
CDC42/GDP	-0.024	0.1	-10000	0	-0.3	15	15
PI3K	0.012	0.065	-10000	0	-0.21	18	18
EFNA5	-0.03	0.13	-10000	0	-0.42	28	28
Ephrin B2/EPHB4	0	0.063	-10000	0	-0.21	22	22
Ephrin B/EPHB2/Intersectin/N-WASP	-0.018	0.092	-10000	0	-0.2	51	51
CDC42	0.014	0	-10000	0	-10000	0	0
RAS family/GTP	-0.052	0.077	-10000	0	-0.31	9	9
PTK2	0.01	0.022	-10000	0	-10000	0	0
MAP4K4	-0.007	0.085	-10000	0	-0.22	27	27
SRC	0.012	0.026	-10000	0	-0.43	1	1
KALRN	-0.001	0.072	-10000	0	-0.35	11	11
Intersectin/N-WASP	0.02	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.023	0.11	-10000	0	-0.28	18	18
MAP2K1	-0.011	0.08	-10000	0	-0.26	4	4
WASL	0.014	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.008	0.093	-10000	0	-0.24	27	27
cell migration	-0.013	0.095	-10000	0	-0.25	8	8
NRAS	0.014	0	-10000	0	-10000	0	0
SYNJ1	-0.022	0.091	-10000	0	-0.19	53	53
PXN	0.014	0	-10000	0	-10000	0	0
TF	-0.097	0.12	-10000	0	-0.33	33	33
HRAS/GTP	-0.036	0.1	-10000	0	-0.3	14	14
Ephrin B1/EPHB1-2	-0.016	0.092	-10000	0	-0.25	27	27
cell adhesion mediated by integrin	0.038	0.081	0.21	42	-10000	0	42
RAC1	0.014	0	-10000	0	-10000	0	0
mol:GTP	-0.038	0.11	-10000	0	-0.32	14	14
RAC1-CDC42/GTP	-0.065	0.093	-10000	0	-0.32	18	18
RASA1	0.009	0.045	-10000	0	-0.43	3	3
RAC1-CDC42/GDP	-0.018	0.1	-10000	0	-0.3	13	13
ruffle organization	-0.032	0.11	-10000	0	-0.32	17	17
NCK1	0.014	0	-10000	0	-10000	0	0
receptor internalization	-0.023	0.096	-10000	0	-0.3	10	10
Ephrin B/EPHB2/KALRN	-0.024	0.1	-10000	0	-0.21	58	58
ROCK1	-0.003	0.07	-10000	0	-0.22	25	25
RAS family/GDP	-0.048	0.077	-10000	0	-0.27	17	17
Rac1/GTP	-0.065	0.095	-10000	0	-0.31	22	22
Ephrin B/EPHB1/Src/Paxillin	-0.025	0.093	-10000	0	-0.21	51	51

×

Arf6 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.007	0.052	-9999	-0.23	13	13
ARNO/beta Arrestin1-2	0.016	0.038	-9999	-10000	0	0
EGFR	-0.028	0.12	-9999	-0.34	33	33
EPHA2	-0.006	0.089	-9999	-0.41	13	13
USP6	0.014	0	-9999	-10000	0	0
IQSEC1	0.013	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.086	0.15	-9999	-0.28	99	99
ARRB2	0.009	0.003	-9999	-10000	0	0
mol:GTP	-0.011	0.058	-9999	-0.19	18	18
ARRB1	0.01	0.037	-9999	-0.43	2	2
FBXO8	0.014	0	-9999	-10000	0	0
TSHR	-0.037	0.13	-9999	-0.36	37	37
EGF	-0.097	0.18	-9999	-0.4	76	76
somatostatin receptor activity	0	0	-9999	-0.001	20	20
ARAP2	-0.019	0.12	-9999	-0.43	21	21
mol:GDP	-0.027	0.067	-9999	-0.2	17	17
mol:PI-3-4-5-P3	0	0	-9999	-0.001	11	11
ITGA2B	-0.028	0.12	-9999	-0.35	32	32
ARF6	0.013	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.024	0.05	-9999	-0.21	11	11
ADAP1	-0.006	0.088	-9999	-0.4	13	13
KIF13B	0.014	0	-9999	-10000	0	0
HGF/MET	-0.052	0.13	-9999	-0.26	72	72
PXN	0.014	0	-9999	-10000	0	0
ARF6/GTP	-0.037	0.076	-9999	-0.22	17	17
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.063	0.13	-9999	-0.26	65	65
ADRB2	-0.004	0.08	-9999	-0.36	13	13
receptor agonist activity	0	0	-9999	0	24	24
actin filament binding	0	0	-9999	0	24	24
SRC	0.012	0.026	-9999	-0.43	1	1
ITGB3	-0.068	0.17	-9999	-0.4	55	55
GNAQ	0.013	0	-9999	-10000	0	0
EFA6/PI-4-5-P2	0	0	-9999	-0.001	14	14
ARF6/GDP	-0.03	0.12	-9999	-0.3	40	40
ARF6/GDP/GULP/ACAP1	-0.054	0.12	-9999	-0.28	41	41
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.032	0.11	-9999	-0.23	53	53
ACAP1	-0.065	0.16	-9999	-0.38	56	56
ACAP2	0.009	0.045	-9999	-0.43	3	3
LHCGR/beta Arrestin2	0.002	0.006	-9999	-10000	0	0
EFNA1	0.014	0	-9999	-10000	0	0
HGF	-0.025	0.11	-9999	-0.36	29	29
CYTH3	0.008	0.019	-9999	-0.3	1	1
CYTH2	0.009	0.001	-9999	-10000	0	0
NCK1	0.014	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	0	19	19
endosomal lumen acidification	0	0	-9999	0	27	27
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.021	0.12	-9999	-0.42	22	22
GNAQ/ARNO	0.017	0.003	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	14	14
MET	-0.051	0.15	-9999	-0.4	44	44
GNA14	-0.027	0.11	-9999	-0.32	34	34
GNA15	-0.006	0.086	-9999	-0.38	14	14
GIT1	0.014	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	16	16
GNA11	0.012	0.026	-9999	-0.43	1	1
LHCGR	0.002	0.005	-9999	-10000	0	0
AGTR1	-0.039	0.13	-9999	-0.37	38	38
desensitization of G-protein coupled receptor protein signaling pathway	0.002	0.006	-9999	-10000	0	0
IPCEF1/ARNO	-0.045	0.098	-9999	-0.32	8	8
alphaIIb/beta3 Integrin	-0.065	0.14	-9999	-0.28	80	80

×

Signaling events mediated by PTP1B

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
PDGFRB	0.009	0.045	-10000	0	-0.43	3	3
Jak2/Leptin Receptor	-0.048	0.14	0.19	1	-0.42	25	26
PTP1B/AKT1	-0.023	0.087	-10000	0	-0.26	22	22
FYN	0.014	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.032	0.095	-10000	0	-0.28	25	25
EGFR	-0.031	0.12	-10000	0	-0.34	33	33
EGF/EGFR	-0.075	0.14	-10000	0	-0.29	71	71
CSF1	0.002	0.067	-10000	0	-0.38	8	8
AKT1	0.013	0.001	-10000	0	-10000	0	0
INSR	0.012	0.027	-10000	0	-0.43	1	1
PTP1B/N-cadherin	-0.087	0.13	-10000	0	-0.28	62	62
Insulin Receptor/Insulin	-0.014	0.072	-10000	0	-0.27	10	10
HCK	-0.004	0.086	-10000	0	-0.43	11	11
CRK	0.014	0	-10000	0	-10000	0	0
TYK2	-0.025	0.091	-10000	0	-0.27	22	22
EGF	-0.099	0.19	-10000	0	-0.4	76	76
YES1	0.006	0.058	-10000	0	-0.43	5	5
CAV1	-0.038	0.11	-10000	0	-0.33	20	20
TXN	0.012	0.003	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.026	0.099	-10000	0	-0.26	30	30
cell migration	0.032	0.095	0.28	25	-10000	0	25
STAT3	0.013	0.001	-10000	0	-10000	0	0
PRLR	-0.083	0.16	-10000	0	-0.36	74	74
ITGA2B	-0.029	0.12	-10000	0	-0.35	32	32
CSF1R	-0.006	0.091	-10000	0	-0.42	13	13
Prolactin Receptor/Prolactin	-0.066	0.13	-10000	0	-0.25	87	87
FGR	-0.007	0.089	-10000	0	-0.39	14	14
PTP1B/p130 Cas	-0.026	0.093	-10000	0	-0.26	25	25
Crk/p130 Cas	-0.018	0.091	-10000	0	-0.26	21	21
DOK1	-0.018	0.088	-10000	0	-0.26	22	22
JAK2	-0.051	0.14	-10000	0	-0.42	25	25
Jak2/Leptin Receptor/Leptin	-0.048	0.12	-10000	0	-0.4	18	18
PIK3R1	0.01	0.037	-10000	0	-0.43	2	2
PTPN1	-0.032	0.096	-10000	0	-0.28	26	26
LYN	0.012	0.026	-10000	0	-0.43	1	1
CDH2	-0.12	0.19	-10000	0	-0.4	90	90
SRC	0.001	0.051	-10000	0	-0.58	1	1
ITGB3	-0.068	0.17	-10000	0	-0.4	55	55
CAT1/PTP1B	-0.063	0.15	-10000	0	-0.39	32	32
CAPN1	0.012	0.027	-10000	0	-0.44	1	1
CSK	0.014	0	-10000	0	-10000	0	0
PI3K	-0.024	0.075	-10000	0	-0.33	10	10
mol:H2O2	-0.001	0.003	-10000	0	-10000	0	0
STAT3 (dimer)	-0.042	0.11	-10000	0	-0.41	15	15
negative regulation of transcription	-0.05	0.14	-10000	0	-0.41	25	25
FCGR2A	0.009	0.042	-10000	0	-0.39	3	3
FER	0.004	0.059	-10000	0	-0.44	5	5
alphaIIb/beta3 Integrin	-0.067	0.14	-10000	0	-0.28	80	80
BLK	-0.085	0.17	-10000	0	-0.36	73	73
Insulin Receptor/Insulin/Shc	0.018	0.016	-10000	0	-0.25	1	1
RHOA	0.013	0.001	-10000	0	-10000	0	0
LEPR	0.002	0.069	-10000	0	-0.4	8	8
BCAR1	0.009	0.045	-10000	0	-0.43	3	3
p210 bcr-abl/Grb2	0.014	0	-10000	0	-10000	0	0
mol:NADPH	-0.001	0.003	-10000	0	-10000	0	0
TRPV6	-0.065	0.17	-10000	0	-0.46	30	30
PRL	-0.014	0.077	-10000	0	-0.31	18	18
SOCS3	-0.011	0.18	-10000	0	-1.2	6	6
SPRY2	0.007	0.05	-10000	0	-0.4	4	4
Insulin Receptor/Insulin/IRS1	0.006	0.057	-10000	0	-0.24	14	14
CSF1/CSF1R	-0.03	0.12	-10000	0	-0.32	31	31
Ras protein signal transduction	0.021	0.028	-10000	0	-10000	0	0
IRS1	-0.006	0.091	-10000	0	-0.42	13	13
INS	0	0.002	-10000	0	-10000	0	0
LEP	-0.023	0.098	-10000	0	-0.31	29	29
STAT5B	-0.036	0.1	-10000	0	-0.28	29	29
STAT5A	-0.037	0.1	-10000	0	-0.28	29	29
GRB2	0.014	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.026	0.096	-10000	0	-0.27	26	26
CSN2	-0.017	0.054	-10000	0	-10000	0	0
PIK3CA	0.007	0.052	-10000	0	-0.43	4	4
LAT	-0.023	0.11	-10000	0	-0.48	14	14
YBX1	0.02	0.01	-10000	0	-10000	0	0
LCK	-0.075	0.17	-10000	0	-0.38	63	63
SHC1	0.014	0	-10000	0	-10000	0	0
NOX4	-0.048	0.15	-10000	0	-0.4	41	41

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.003	0.056	-10000	0	-0.31	9	9
EPHB2	-0.012	0.1	-10000	0	-0.42	17	17
EFNB1	0.008	0.055	-10000	0	-0.25	12	12
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.016	0.11	-10000	0	-0.36	15	15
Ephrin B2/EPHB1-2	-0.02	0.098	-10000	0	-0.22	42	42
neuron projection morphogenesis	-0.045	0.092	-10000	0	-0.34	15	15
Ephrin B1/EPHB1-2/Tiam1	-0.023	0.12	-10000	0	-0.26	42	42
DNM1	-0.002	0.076	-10000	0	-0.37	11	11
cell-cell signaling	0	0.002	-10000	0	-10000	0	0
MAP2K4	-0.018	0.13	-10000	0	-0.49	18	18
YES1	-0.041	0.18	-10000	0	-0.8	15	15
Ephrin B1/EPHB1-2/NCK2	-0.009	0.1	-10000	0	-0.24	30	30
PI3K	-0.015	0.14	-10000	0	-0.5	19	19
mol:GDP	-0.024	0.12	-10000	0	-0.26	42	42
ITGA2B	-0.028	0.12	-10000	0	-0.35	32	32
endothelial cell proliferation	0	0.063	-10000	0	-0.21	22	22
FYN	-0.039	0.18	-10000	0	-0.78	15	15
MAP3K7	-0.025	0.14	-10000	0	-0.52	18	18
FGR	-0.038	0.18	-10000	0	-0.77	15	15
TIAM1	-0.014	0.11	-10000	0	-0.42	18	18
PIK3R1	0.01	0.037	-10000	0	-0.43	2	2
RGS3	0.012	0.026	-10000	0	-0.43	1	1
cell adhesion	-0.06	0.17	-10000	0	-0.52	23	23
LYN	-0.039	0.18	-10000	0	-0.78	15	15
Ephrin B1/EPHB1-2/Src Family Kinases	-0.039	0.16	-10000	0	-0.73	15	15
Ephrin B1/EPHB1-2	-0.037	0.14	-10000	0	-0.63	15	15
SRC	-0.032	0.18	-10000	0	-0.77	15	15
ITGB3	-0.068	0.17	-10000	0	-0.4	55	55
EPHB1	-0.039	0.13	-10000	0	-0.35	41	41
EPHB4	-0.007	0.093	-10000	0	-0.43	13	13
RAC1	0.014	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0	0.064	-10000	0	-0.22	22	22
alphaIIb/beta3 Integrin	-0.065	0.14	-10000	0	-0.28	80	80
BLK	-0.061	0.18	-10000	0	-0.79	15	15
HCK	-0.045	0.18	-10000	0	-0.77	15	15
regulation of stress fiber formation	0.01	0.099	0.24	30	-10000	0	30
MAPK8	-0.015	0.13	-10000	0	-0.52	16	16
Ephrin B1/EPHB1-2/RGS3	-0.01	0.1	-10000	0	-0.25	30	30
endothelial cell migration	-0.028	0.12	-10000	0	-0.36	27	27
NCK2	0.014	0	-10000	0	-10000	0	0
PTPN13	-0.014	0.13	-10000	0	-0.54	15	15
regulation of focal adhesion formation	0.01	0.099	0.24	30	-10000	0	30
chemotaxis	0.01	0.1	0.25	30	-10000	0	30
PIK3CA	0.007	0.052	-10000	0	-0.43	4	4
Rac1/GTP	-0.02	0.11	-10000	0	-0.35	15	15
angiogenesis	-0.036	0.14	-10000	0	-0.63	15	15
LCK	-0.056	0.18	-10000	0	-0.79	15	15

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.012	0.049	-9999	-0.3	7	7
VLDLR	0.001	0.071	-9999	-0.41	8	8
CRKL	0.012	0.019	-9999	-0.31	1	1
LRPAP1	0.014	0	-9999	-10000	0	0
FYN	0.014	0	-9999	-10000	0	0
ITGA3	-0.02	0.12	-9999	-0.41	22	22
RELN/VLDLR/Fyn	-0.039	0.11	-9999	-0.26	30	30
MAPK8IP1/MKK7/MAP3K11/JNK1	0.023	0.061	-9999	-0.19	20	20
AKT1	-0.025	0.088	-9999	-0.22	34	34
MAP2K7	0.014	0	-9999	-10000	0	0
RAPGEF1	0.014	0	-9999	-10000	0	0
DAB1	-0.026	0.097	-9999	-0.31	30	30
RELN/LRP8/DAB1	-0.049	0.1	-9999	-0.23	49	49
LRPAP1/LRP8	0.019	0.019	-9999	-0.3	1	1
RELN/LRP8/DAB1/Fyn	-0.039	0.1	-9999	-0.24	37	37
DAB1/alpha3/beta1 Integrin	-0.068	0.1	-9999	-0.31	31	31
long-term memory	-0.056	0.12	-9999	-0.3	33	33
DAB1/LIS1	-0.033	0.1	-9999	-0.24	33	33
DAB1/CRLK/C3G	-0.053	0.082	-9999	-0.27	20	20
PIK3CA	0.007	0.052	-9999	-0.43	4	4
DAB1/NCK2	-0.033	0.1	-9999	-0.28	20	20
ARHGEF2	0.014	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.027	0.11	-9999	-0.34	32	32
CDK5R1	0.003	0.069	-9999	-0.43	7	7
RELN	-0.087	0.16	-9999	-0.34	79	79
PIK3R1	0.01	0.037	-9999	-0.43	2	2
RELN/LRP8/Fyn	-0.033	0.1	-9999	-0.25	24	24
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.051	0.12	-9999	-0.25	51	51
MAPK8	0.007	0.052	-9999	-0.43	4	4
RELN/VLDLR/DAB1	-0.054	0.11	-9999	-0.26	43	43
ITGB1	0.011	0.032	-9999	-0.37	2	2
MAP1B	-0.051	0.11	-9999	-0.24	54	54
RELN/LRP8	-0.033	0.1	-9999	-0.19	79	79
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.045	0.11	-9999	-0.25	44	44
PI3K	0.014	0.05	-9999	-0.35	5	5
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.005	0.084	-9999	-0.28	24	24
RAP1A	-0.022	0.094	-9999	-0.25	20	20
PAFAH1B1	0.014	0	-9999	-10000	0	0
MAPK8IP1	-0.011	0.1	-9999	-0.42	16	16
CRLK/C3G	0.019	0.013	-9999	-0.2	1	1
GRIN2B	-0.014	0.079	-9999	-0.31	19	19
NCK2	0.014	0	-9999	-10000	0	0
neuron differentiation	-0.012	0.079	-9999	-0.3	7	7
neuron adhesion	-0.027	0.11	-9999	-0.31	19	19
LRP8	0.012	0.026	-9999	-0.43	1	1
GSK3B	-0.019	0.084	-9999	-0.31	8	8
RELN/VLDLR/DAB1/Fyn	-0.044	0.11	-9999	-0.24	43	43
MAP3K11	0.012	0.026	-9999	-0.43	1	1
RELN/VLDLR/DAB1/P13K	-0.033	0.094	-9999	-0.24	34	34
CDK5	0.014	0	-9999	-10000	0	0
MAPT	-0.036	0.13	-9999	-0.36	36	36
neuron migration	-0.013	0.1	-9999	-0.27	27	27
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.012	0.08	-9999	-0.3	7	7
RELN/VLDLR	-0.027	0.1	-9999	-0.24	30	30

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.006	0.15	-10000	0	-1.1	5	5
VDR	0.007	0.052	-10000	0	-0.43	4	4
FAM120B	0.014	0	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.023	0.13	-10000	0	-0.32	22	22
RXRs/LXRs/DNA/Oxysterols	-0.023	0.16	-10000	0	-0.46	22	22
MED1	0.014	0	-10000	0	-10000	0	0
mol:9cRA	0.001	0.014	-10000	0	-10000	0	0
RARs/THRs/DNA/Src-1	-0.011	0.093	-10000	0	-0.23	35	35
RXRs/NUR77	-0.02	0.11	-10000	0	-0.22	64	64
RXRs/PPAR	-0.023	0.1	-10000	0	-0.2	68	68
NCOR2	0.012	0.026	-10000	0	-0.43	1	1
VDR/VDR/Vit D3	0.006	0.037	-10000	0	-0.3	4	4
RARs/VDR/DNA/Vit D3	0.007	0.073	-10000	0	-0.21	27	27
RARA	0.014	0	-10000	0	-10000	0	0
NCOA1	0.014	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.007	0.052	-10000	0	-0.43	4	4
RARs/RARs/DNA/9cRA	0.003	0.067	-10000	0	-0.2	25	25
RARG	0.014	0	-10000	0	-10000	0	0
RPS6KB1	0.013	0.063	-10000	0	-0.4	5	5
RARs/THRs/DNA/SMRT	-0.012	0.094	-10000	0	-0.41	6	6
THRA	0.014	0	-10000	0	-10000	0	0
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.006	0.037	-10000	0	-0.3	4	4
RXRs/PPAR/9cRA/PGJ2/DNA	-0.023	0.11	0.28	2	-0.22	64	66
NR1H4	-0.008	0.063	-10000	0	-0.31	12	12
RXRs/LXRs/DNA	-0.007	0.12	-10000	0	-0.34	10	10
NR1H2	0.014	0.03	-10000	0	-0.45	1	1
NR1H3	0.014	0.033	-10000	0	-0.49	1	1
RXRs/VDR/DNA/Vit D3	-0.019	0.1	-10000	0	-0.2	65	65
NR4A1	0.008	0.049	-10000	0	-0.4	4	4
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.025	0.09	-10000	0	-0.18	63	63
RXRG	-0.086	0.19	-10000	0	-0.42	65	65
RXR alpha/CCPG	0.021	0.008	-10000	0	-10000	0	0
RXRA	0.015	0.012	-10000	0	-10000	0	0
RXRB	0.015	0.013	-10000	0	-10000	0	0
THRB	-0.047	0.14	-10000	0	-0.35	47	47
PPARG	0.002	0.069	-10000	0	-0.4	8	8
PPARD	0.014	0	-10000	0	-10000	0	0
TNF	-0.049	0.25	-10000	0	-0.9	19	19
mol:Oxysterols	0.002	0.013	-10000	0	-10000	0	0
cholesterol transport	-0.023	0.16	-10000	0	-0.45	22	22
PPARA	0.014	0	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	-0.03	0.13	-10000	0	-0.41	29	29
RXRs/NUR77/BCL2	-0.034	0.12	-10000	0	-0.22	69	69
SREBF1	-0.016	0.16	-10000	0	-0.65	8	8
RXRs/RXRs/DNA/9cRA	-0.023	0.11	0.27	2	-0.22	64	66
ABCA1	-0.026	0.2	-10000	0	-0.82	11	11
RARs/THRs	-0.013	0.1	-10000	0	-0.23	36	36
RXRs/FXR	-0.028	0.11	-10000	0	-0.22	63	63
BCL2	0.001	0.074	-10000	0	-0.43	8	8

×

Effects of Botulinum toxin

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
STX1A	0.002	0.042	-9999	-0.22	10	10
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	0.007	0.042	-9999	-0.21	10	10
STXBP1	0.012	0.026	-9999	-0.43	1	1
ACh/CHRNA1	-0.059	0.11	-9999	-0.25	65	65
RAB3GAP2/RIMS1/UNC13B	0.015	0.039	-9999	-0.25	2	2
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	-0.004	0.055	-9999	-0.31	9	9
mol:ACh	-0.016	0.04	-9999	-0.1	41	41
RAB3GAP2	0.012	0.026	-9999	-0.43	1	1
STX1A/SNAP25/VAMP2	-0.018	0.056	-9999	-0.22	1	1
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.059	0.11	-9999	-0.25	65	65
UNC13B	0.012	0.026	-9999	-0.43	1	1
CHRNA1	-0.077	0.17	-9999	-0.38	65	65
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.048	0.092	-9999	-0.21	61	61
SNAP25	-0.043	0.088	-9999	-0.16	83	83
VAMP2	0.006	0	-9999	-10000	0	0
SYT1	-0.061	0.14	-9999	-0.33	61	61
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	0.01	0.039	-9999	-0.18	11	11
STX1A/SNAP25 fragment 1/VAMP2	-0.018	0.056	-9999	-0.22	1	1

×

Neurotrophic factor-mediated Trk receptor 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
CRKL	0.012	0.019	-10000	0	-0.31	1	1
RAS family/GTP/Tiam1	-0.007	0.068	-10000	0	-0.2	18	18
NT3 (dimer)/TRKC	-0.039	0.12	-10000	0	-0.26	58	58
NT3 (dimer)/TRKB	-0.081	0.15	-10000	0	-0.3	64	64
SHC/Grb2/SOS1/GAB1/PI3K	0.026	0.054	-10000	0	-0.28	6	6
RAPGEF1	0.014	0	-10000	0	-10000	0	0
BDNF	-0.099	0.18	-10000	0	-0.37	82	82
PIK3CA	0.007	0.052	-10000	0	-0.43	4	4
DYNLT1	0.014	0	-10000	0	-10000	0	0
NTRK1	-0.014	0.099	-10000	0	-0.37	20	20
NTRK2	-0.052	0.14	-10000	0	-0.36	49	49
NTRK3	-0.035	0.12	-10000	0	-0.34	38	38
NT-4/5 (dimer)/TRKB	-0.072	0.14	-10000	0	-0.3	56	56
neuron apoptosis	0.13	0.18	0.39	73	-0.19	1	74
SHC 2-3/Grb2	-0.14	0.2	0.19	1	-0.42	73	74
SHC1	0.014	0	-10000	0	-10000	0	0
SHC2	-0.13	0.21	0.18	1	-0.47	63	64
SHC3	-0.11	0.19	0.18	1	-0.47	45	46
STAT3 (dimer)	0.017	0.036	-10000	0	-0.31	3	3
NT3 (dimer)/TRKA	-0.06	0.13	-10000	0	-0.29	48	48
RIN/GDP	-0.008	0.059	-10000	0	-0.17	4	4
GIPC1	0.014	0	-10000	0	-10000	0	0
KRAS	0.012	0.019	-10000	0	-0.31	1	1
DNAJA3	-0.043	0.11	0.21	1	-0.24	52	53
RIN/GTP	0	0.013	-10000	0	-0.21	1	1
CCND1	0.018	0.075	-10000	0	-0.67	3	3
MAGED1	0.012	0.026	-10000	0	-0.43	1	1
PTPN11	0.014	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.008	0.066	-10000	0	-0.31	13	13
SHC/GRB2/SOS1	0.028	0	-10000	0	-10000	0	0
GRB2	0.014	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.036	0.11	-10000	0	-0.26	42	42
TRKA/NEDD4-2	-0.002	0.076	-10000	0	-0.25	23	23
ELMO1	0.001	0.069	-10000	0	-0.37	9	9
RhoG/GTP/ELMO1/DOCK1	0.011	0.041	-10000	0	-0.21	9	9
NGF	-0.02	0.11	-10000	0	-0.38	24	24
HRAS	0.014	0	-10000	0	-10000	0	0
DOCK1	0.014	0	-10000	0	-10000	0	0
GAB2	0.011	0.027	-10000	0	-0.31	2	2
RIT2	0	0.019	-10000	0	-0.31	1	1
RIT1	0.014	0	-10000	0	-10000	0	0
FRS2	0.011	0.027	-10000	0	-0.31	2	2
DNM1	-0.002	0.076	-10000	0	-0.37	11	11
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	-0.046	0.11	0.2	1	-0.24	55	56
mol:GDP	-0.012	0.081	-10000	0	-0.24	5	5
NGF (dimer)	-0.02	0.11	-10000	0	-0.38	24	24
RhoG/GDP	0.001	0.048	-10000	0	-0.26	9	9
RIT1/GDP	-0.003	0.06	-10000	0	-0.17	4	4
TIAM1	-0.014	0.11	-10000	0	-0.42	18	18
PIK3R1	0.01	0.037	-10000	0	-0.43	2	2
BDNF (dimer)/TRKB	-0.078	0.14	-10000	0	-0.23	116	116
KIDINS220/CRKL/C3G	0.019	0.013	-10000	0	-0.2	1	1
SHC/RasGAP	0.017	0.032	-10000	0	-0.3	3	3
FRS2 family/SHP2	0.026	0.016	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0.033	0.021	-10000	0	-0.21	2	2
RIT1/GTP	0.01	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.024	0.1	-10000	0	-0.31	31	31
RAP1/GDP	-0.02	0.037	-10000	0	-0.15	2	2
KIDINS220/CRKL	0.012	0.019	-10000	0	-0.31	1	1
BDNF (dimer)	-0.099	0.18	-10000	0	-0.37	82	82
ubiquitin-dependent protein catabolic process	-0.012	0.091	-10000	0	-0.25	29	29
Schwann cell development	-0.03	0.027	-10000	0	-10000	0	0
EHD4	0.014	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.034	0.014	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.034	0.01	-10000	0	-10000	0	0
RAP1B	0.012	0.019	-10000	0	-0.31	1	1
RAP1A	0.014	0	-10000	0	-10000	0	0
CDC42/GTP	-0.12	0.13	-10000	0	-0.32	64	64
ABL1	0.014	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.02	0	-10000	0	-10000	0	0
Rap1/GTP	-0.002	0.06	-10000	0	-10000	0	0
STAT3	0.017	0.036	-10000	0	-0.31	3	3
axon guidance	-0.12	0.13	-10000	0	-0.31	64	64
MAPK3	-0.029	0.1	-10000	0	-0.24	41	41
MAPK1	-0.029	0.1	-10000	0	-0.24	41	41
CDC42/GDP	-0.003	0.06	-10000	0	-0.17	3	3
NTF3	-0.024	0.1	-10000	0	-0.31	31	31
NTF4	-0.008	0.066	-10000	0	-0.31	13	13
NGF (dimer)/TRKA/FAIM	-0.014	0.092	-10000	0	-0.24	31	31
PI3K	0.014	0.05	-10000	0	-0.35	5	5
FRS3	0.014	0	-10000	0	-10000	0	0
FAIM	0.006	0.058	-10000	0	-0.43	5	5
GAB1	0.01	0.037	-10000	0	-0.43	2	2
RASGRF1	-0.086	0.13	0.21	1	-0.25	84	85
SOS1	0.014	0	-10000	0	-10000	0	0
MCF2L	-0.061	0.12	-10000	0	-0.26	58	58
RGS19	0.014	0	-10000	0	-10000	0	0
CDC42	0.014	0	-10000	0	-10000	0	0
RAS family/GTP	0.007	0.055	-10000	0	-10000	0	0
Rac1/GDP	-0.003	0.06	-10000	0	-0.17	4	4
NGF (dimer)/TRKA/GRIT	-0.018	0.086	-10000	0	-0.22	43	43
neuron projection morphogenesis	-0.031	0.11	-10000	0	-0.4	5	5
NGF (dimer)/TRKA/NEDD4-2	-0.012	0.091	-10000	0	-0.25	29	29
MAP2K1	0.03	0.019	-10000	0	-0.19	2	2
NGFR	-0.071	0.16	-10000	0	-0.36	64	64
NGF (dimer)/TRKA/GIPC/GAIP	0	0.078	-10000	0	-0.52	1	1
RAS family/GTP/PI3K	0.022	0.038	-10000	0	-0.24	5	5
FRS2 family/SHP2/GRB2/SOS1	0.039	0.014	-10000	0	-10000	0	0
NRAS	0.014	0	-10000	0	-10000	0	0
GRB2/SOS1	0.02	0	-10000	0	-10000	0	0
PRKCI	0.007	0.052	-10000	0	-0.43	4	4
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.014	0	-10000	0	-10000	0	0
PRKCZ	0.003	0.069	-10000	0	-0.43	7	7
MAPKKK cascade	-0.079	0.19	-10000	0	-0.6	29	29
RASA1	0.009	0.045	-10000	0	-0.43	3	3
TRKA/c-Abl	0.001	0.07	-10000	0	-0.25	20	20
SQSTM1	0.014	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.062	0.12	-10000	0	-0.24	69	69
NGF (dimer)/TRKA/p62/Atypical PKCs	0	0.084	-10000	0	-0.2	36	36
MATK	-0.033	0.13	-10000	0	-0.38	33	33
NEDD4L	0.009	0.045	-10000	0	-0.43	3	3
RAS family/GDP	-0.02	0.035	-10000	0	-0.15	1	1
NGF (dimer)/TRKA	-0.051	0.11	0.22	1	-0.26	52	53
Rac1/GTP	-0.065	0.083	-10000	0	-0.23	40	40
FRS2 family/SHP2/CRK family	0.039	0.017	-10000	0	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.025	0.11	-10000	0	-0.27	44	44
CRKL	-0.017	0.1	-10000	0	-0.24	34	34
mol:PIP3	-0.004	0.063	0.39	7	-10000	0	7
AKT1	0.008	0.045	0.29	7	-10000	0	7
PTK2B	0.01	0.037	-10000	0	-0.35	3	3
RAPGEF1	-0.01	0.099	-10000	0	-0.51	3	3
RANBP10	0.014	0	-10000	0	-10000	0	0
PIK3CA	0.007	0.052	-10000	0	-0.43	4	4
HGF/MET/SHIP2	-0.034	0.11	-10000	0	-0.24	45	45
MAP3K5	-0.022	0.12	-10000	0	-0.39	11	11
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.022	0.1	-10000	0	-0.22	45	45
AP1	-0.001	0.043	-10000	0	-0.17	7	7
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.014	0	-10000	0	-10000	0	0
apoptosis	0.005	0.03	-10000	0	-10000	0	0
STAT3 (dimer)	-0.013	0.091	-10000	0	-0.4	2	2
GAB1/CRKL/SHP2/PI3K	-0.001	0.11	-10000	0	-0.57	3	3
INPP5D	-0.009	0.095	-10000	0	-0.39	16	16
CBL/CRK	-0.008	0.1	-10000	0	-0.51	3	3
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	0.003	0.069	-10000	0	-0.43	7	7
ELK1	-0.025	0.054	-10000	0	-0.15	44	44
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.005	0.061	-10000	0	-0.21	5	5
PAK1	0.011	0.045	0.27	7	-0.2	1	8
HGF/MET/RANBP10	-0.034	0.11	-10000	0	-0.21	72	72
HRAS	-0.053	0.19	-10000	0	-0.54	33	33
DOCK1	-0.01	0.099	-10000	0	-0.51	3	3
GAB1	-0.023	0.11	-10000	0	-0.26	34	34
CRK	-0.016	0.1	-10000	0	-0.55	3	3
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.056	0.18	-10000	0	-0.47	45	45
JUN	0.014	0	-10000	0	-10000	0	0
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.031	0.085	-10000	0	-0.21	47	47
PIK3R1	0.01	0.037	-10000	0	-0.43	2	2
cell morphogenesis	-0.001	0.11	-10000	0	-0.48	3	3
GRB2/SHC	-0.012	0.078	-10000	0	-0.19	35	35
FOS	0.006	0.05	-10000	0	-0.31	7	7
GLMN	-0.004	0.03	-10000	0	-0.23	5	5
cell motility	-0.025	0.054	-10000	0	-0.15	44	44
HGF/MET/MUC20	-0.042	0.11	-10000	0	-0.22	72	72
cell migration	-0.012	0.077	-10000	0	-0.19	35	35
GRB2	0.014	0	-10000	0	-10000	0	0
CBL	0.014	0	-10000	0	-10000	0	0
MET/RANBP10	-0.025	0.11	-10000	0	-0.27	44	44
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.017	0.091	-10000	0	-0.2	48	48
MET/MUC20	-0.035	0.11	-10000	0	-0.28	44	44
RAP1B	-0.005	0.094	-10000	0	-0.47	3	3
RAP1A	-0.004	0.094	-10000	0	-0.47	3	3
HGF/MET/RANBP9	-0.034	0.11	-10000	0	-0.24	45	45
RAF1	-0.044	0.18	-10000	0	-0.51	33	33
STAT3	-0.013	0.092	-10000	0	-0.41	2	2
cell proliferation	-0.021	0.13	-10000	0	-0.3	45	45
RPS6KB1	-0.008	0.038	-10000	0	-10000	0	0
MAPK3	-0.027	0.049	-10000	0	-10000	0	0
MAPK1	-0.027	0.049	-10000	0	-10000	0	0
RANBP9	0.014	0	-10000	0	-10000	0	0
MAPK8	-0.007	0.12	-10000	0	-0.48	8	8
SRC	-0.011	0.086	-10000	0	-0.37	2	2
PI3K	-0.017	0.087	-10000	0	-0.2	39	39
MET/Glomulin	-0.03	0.095	-10000	0	-0.23	49	49
SOS1	0.014	0	-10000	0	-10000	0	0
MAP2K1	-0.036	0.17	-10000	0	-0.47	33	33
MET	-0.051	0.15	-10000	0	-0.4	44	44
MAP4K1	-0.025	0.12	-10000	0	-0.4	9	9
PTK2	0.014	0	-10000	0	-10000	0	0
MAP2K2	-0.036	0.17	-10000	0	-0.47	33	33
BAD	0.012	0.043	0.27	7	-0.21	1	8
MAP2K4	-0.015	0.11	-10000	0	-0.38	9	9
SHP2/GRB2/SOS1/GAB1	-0.046	0.1	-10000	0	-0.3	34	34
INPPL1	0.014	0	-10000	0	-10000	0	0
PXN	0.014	0	-10000	0	-10000	0	0
SH3KBP1	0.012	0.026	-10000	0	-0.43	1	1
HGS	-0.023	0.079	-10000	0	-0.19	47	47
PLCgamma1/PKC	0.01	0	-10000	0	-10000	0	0
HGF	-0.025	0.11	-10000	0	-0.36	29	29
RASA1	0.009	0.045	-10000	0	-0.43	3	3
NCK1	0.014	0	-10000	0	-10000	0	0
PTPRJ	0.01	0.037	-10000	0	-0.43	2	2
NCK/PLCgamma1	-0.011	0.079	-10000	0	-0.18	47	47
PDPK1	0.003	0.051	0.32	7	-10000	0	7
HGF/MET/SHIP	-0.047	0.12	-10000	0	-0.27	50	50

×

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

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
BAG4	0.007	0.052	-9999	-0.43	4	4
Caspase 8 (4 units)	-0.016	0.1	-9999	-0.34	10	10
NEF	-0.025	0.055	-9999	-0.17	25	25
NFKBIA	0.001	0.033	-9999	-10000	0	0
BIRC3	-0.034	0.16	-9999	-0.39	47	47
CYCS	-0.02	0.11	-9999	-0.23	48	48
RIPK1	0.014	0	-9999	-10000	0	0
CD247	-0.085	0.18	-9999	-0.46	49	49
MAP2K7	-0.011	0.096	-9999	-0.32	9	9
protein ubiquitination	0.017	0.07	-9999	-0.23	8	8
CRADD	0.011	0.027	-9999	-0.31	2	2
DAXX	0.014	0	-9999	-10000	0	0
FAS	0.006	0.058	-9999	-0.43	5	5
BID	-0.027	0.11	-9999	-0.25	48	48
NF-kappa-B/RelA/I kappa B alpha	-0.002	0.091	-9999	-0.23	29	29
TRADD	0.014	0	-9999	-10000	0	0
MAP3K5	0.005	0.059	-9999	-0.39	6	6
CFLAR	0.012	0.026	-9999	-0.43	1	1
FADD	0.012	0.019	-9999	-0.31	1	1
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.002	0.091	-9999	-0.24	29	29
MAPK8	-0.008	0.095	-9999	-0.31	9	9
APAF1	0.007	0.052	-9999	-0.43	4	4
TRAF1	-0.022	0.1	-9999	-0.33	29	29
TRAF2	0.014	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.033	0.12	-9999	-0.26	49	49
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.007	0.083	-9999	-0.28	11	11
CHUK	0.017	0.074	-9999	-0.25	8	8
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.03	0.046	-9999	-0.19	10	10
TCRz/NEF	-0.086	0.18	-9999	-0.33	85	85
TNF	-0.021	0.11	-9999	-0.38	25	25
FASLG	-0.12	0.24	-9999	-0.49	76	76
NFKB1	0.001	0.033	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	0.003	0.074	-9999	-0.21	29	29
CASP6	0.004	0.083	-9999	-0.42	3	3
CASP7	-0.032	0.18	-9999	-0.49	30	30
RELA	0.001	0.033	-9999	-10000	0	0
CASP2	0.012	0.026	-9999	-0.43	1	1
CASP3	-0.032	0.18	-9999	-0.49	30	30
TNFRSF1A	0.014	0	-9999	-10000	0	0
TNFR1A/BAG4	0.016	0.037	-9999	-0.3	4	4
CASP8	0.012	0.026	-9999	-0.43	1	1
CASP9	0.014	0	-9999	-10000	0	0
MAP3K14	0.013	0.078	-9999	-0.26	11	11
APAF-1/Caspase 9	-0.07	0.12	-9999	-0.34	38	38
BCL2	-0.007	0.096	-9999	-0.29	11	11

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.017	0.16	-9999	-0.52	21	21
MAP3K8	-0.004	0.08	-9999	-0.36	13	13
FOS	-0.028	0.17	-9999	-0.5	24	24
PRKCA	-0.003	0.084	-9999	-0.4	12	12
PTPN7	-0.03	0.13	-9999	-0.38	32	32
HRAS	0.014	0	-9999	-10000	0	0
PRKCB	-0.048	0.15	-9999	-0.38	44	44
NRAS	0.014	0	-9999	-10000	0	0
RAS family/GTP	0.027	0.01	-9999	-10000	0	0
MAPK3	-0.028	0.16	-9999	-0.56	20	20
MAP2K1	-0.026	0.14	-9999	-0.38	37	37
ELK1	0.014	0.001	-9999	-10000	0	0
BRAF	-0.03	0.14	-9999	-0.36	38	38
mol:GTP	0	0	-9999	-0.003	6	6
MAPK1	-0.028	0.16	-9999	-0.56	20	20
RAF1	-0.027	0.14	-9999	-0.37	36	36
KRAS	0.012	0.019	-9999	-0.31	1	1

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.02	0.12	-9999	-0.4	24	24
PDGF/PDGFRA/CRKL	-0.004	0.08	-9999	-0.26	25	25
positive regulation of JUN kinase activity	0.016	0.06	-9999	-0.2	17	17
CRKL	0.012	0.019	-9999	-0.31	1	1
PDGF/PDGFRA/Caveolin-3	-0.013	0.081	-9999	-0.26	27	27
AP1	0.012	0.073	-9999	-0.4	3	3
mol:IP3	-0.003	0.083	-9999	-0.27	24	24
PLCG1	-0.003	0.083	-9999	-0.27	24	24
PDGF/PDGFRA/alphaV Integrin	-0.011	0.094	-9999	-0.28	30	30
RAPGEF1	0.014	0	-9999	-10000	0	0
CRK	0.014	0	-9999	-10000	0	0
mol:Ca2+	-0.003	0.082	-9999	-0.27	24	24
CAV3	-0.001	0.032	-9999	-0.31	3	3
CAV1	0.01	0.037	-9999	-0.43	2	2
SHC/Grb2/SOS1	0.017	0.061	-9999	-0.2	17	17
PDGF/PDGFRA/Shf	-0.011	0.091	-9999	-0.26	32	32
FOS	0.012	0.073	-9999	-0.4	3	3
JUN	-0.002	0.008	-9999	-10000	0	0
oligodendrocyte development	-0.011	0.094	-9999	-0.28	30	30
GRB2	0.014	0	-9999	-10000	0	0
PIK3R1	0.01	0.037	-9999	-0.43	2	2
mol:DAG	-0.003	0.083	-9999	-0.27	24	24
PDGF/PDGFRA	-0.02	0.12	-9999	-0.39	24	24
actin cytoskeleton reorganization	-0.027	0.11	-9999	-0.28	45	45
SRF	0.018	0.003	-9999	-10000	0	0
SHC1	0.014	0	-9999	-10000	0	0
PI3K	0.003	0.081	-9999	-0.23	28	28
PDGF/PDGFRA/Crk/C3G	0.008	0.067	-9999	-0.23	18	18
JAK1	-0.003	0.079	-9999	-0.26	24	24
ELK1/SRF	0.013	0.062	-9999	-0.22	17	17
SHB	-0.02	0.11	-9999	-0.4	23	23
SHF	0.002	0.067	-9999	-0.38	8	8
CSNK2A1	0.011	0.007	-9999	-10000	0	0
GO:0007205	-0.004	0.087	-9999	-0.28	24	24
SOS1	0.014	0	-9999	-10000	0	0
Ras protein signal transduction	0.016	0.06	-9999	-0.2	17	17
PDGF/PDGFRA/SHB	-0.027	0.11	-9999	-0.28	45	45
PDGF/PDGFRA/Caveolin-1	-0.005	0.086	-9999	-0.27	25	25
ITGAV	0.003	0.069	-9999	-0.43	7	7
ELK1	0.003	0.075	-9999	-0.27	18	18
PIK3CA	0.007	0.052	-9999	-0.43	4	4
PDGF/PDGFRA/Crk	-0.003	0.079	-9999	-0.26	24	24
JAK-STAT cascade	-0.003	0.079	-9999	-0.26	24	24
cell proliferation	-0.011	0.09	-9999	-0.26	32	32

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.066	0.17	-9999	-0.42	52	52
CDC42/GTP	-0.041	0.12	-9999	-0.4	14	14
PLCG1	-0.044	0.12	-9999	-0.41	14	14
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	0.02	0	-9999	-10000	0	0
cell migration	-0.041	0.12	-9999	-0.39	14	14
S1PR5	-0.013	0.096	-9999	-0.35	21	21
S1PR4	-0.034	0.13	-9999	-0.38	34	34
MAPK3	-0.044	0.12	-9999	-0.41	14	14
MAPK1	-0.044	0.12	-9999	-0.41	14	14
S1P/S1P5/Gi	-0.041	0.12	-9999	-0.24	55	55
GNAI1	0.006	0.056	-9999	-0.4	5	5
CDC42/GDP	0.01	0	-9999	-10000	0	0
S1P/S1P5/G12	0.003	0.056	-9999	-0.19	21	21
RHOA	0.003	0.064	-9999	-0.2	20	20
S1P/S1P4/Gi	-0.052	0.13	-9999	-0.25	65	65
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.029	0.13	-9999	-0.42	28	28
S1P/S1P4/G12/G13	0.001	0.07	-9999	-0.19	34	34
GNA12	0.014	0	-9999	-10000	0	0
GNA13	0.014	0	-9999	-10000	0	0
CDC42	0.014	0	-9999	-10000	0	0

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.014	0	-9999	-10000	0	0
LAT2	-0.029	0.15	-9999	-0.43	22	22
AP1	-0.018	0.16	-9999	-0.49	22	22
mol:PIP3	-0.043	0.18	-9999	-0.44	34	34
IKBKB	-0.019	0.1	-9999	-0.24	33	33
AKT1	-0.009	0.097	-9999	-0.35	9	9
IKBKG	-0.019	0.1	-9999	-0.25	31	31
MS4A2	-0.018	0.1	-9999	-0.37	21	21
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.007	0.053	-9999	-0.43	4	4
MAP3K1	-0.018	0.15	-9999	-0.44	22	22
mol:Ca2+	-0.028	0.13	-9999	-0.32	34	34
LYN	0.011	0.028	-9999	-0.46	1	1
CBLB	-0.021	0.13	-9999	-0.38	19	19
SHC1	0.013	0	-9999	-10000	0	0
RasGAP/p62DOK	0.019	0.037	-9999	-0.22	4	4
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	-0.009	0.095	-9999	-0.39	16	16
PLD2	-0.025	0.1	-9999	-0.25	32	32
PTPN13	-0.024	0.13	-9999	-0.54	10	10
PTPN11	0.012	0.007	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	0.005	0.092	-9999	-0.3	11	11
SYK	-0.012	0.1	-9999	-0.41	17	17
GRB2	0.013	0	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.078	0.16	-9999	-0.44	35	35
LAT	-0.037	0.14	-9999	-0.38	27	27
PAK2	-0.022	0.16	-9999	-0.54	18	18
NFATC2	-0.06	0.14	-9999	-0.46	28	28
HRAS	-0.032	0.18	-9999	-0.56	20	20
GAB2	0.011	0.027	-9999	-0.31	2	2
PLA2G1B	0.025	0.014	-9999	-10000	0	0
Fc epsilon R1	-0.046	0.13	-9999	-0.26	60	60
Antigen/IgE/Fc epsilon R1	-0.041	0.12	-9999	-0.24	60	60
mol:GDP	-0.039	0.19	-9999	-0.6	21	21
JUN	0.014	0	-9999	-10000	0	0
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.01	0.037	-9999	-0.43	2	2
FOS	0.006	0.05	-9999	-0.31	7	7
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.028	0.14	-9999	-0.39	20	20
CHUK	-0.02	0.1	-9999	-0.25	30	30
KLRG1	-0.024	0.12	-9999	-0.45	12	12
VAV1	-0.038	0.16	-9999	-0.42	28	28
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.021	0.13	-9999	-0.38	19	19
negative regulation of mast cell degranulation	-0.025	0.14	-9999	-0.5	15	15
BTK	-0.039	0.19	-9999	-0.7	17	17
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.037	0.15	-9999	-0.48	18	18
GAB2/PI3K/SHP2	-0.045	0.087	-9999	-0.32	15	15
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.038	0.15	-9999	-0.3	42	42
RAF1	0.016	0.017	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.045	0.14	-9999	-0.31	41	41
FCER1G	-0.019	0.11	-9999	-0.36	25	25
FCER1A	-0.049	0.14	-9999	-0.38	44	44
Antigen/IgE/Fc epsilon R1/Fyn	-0.03	0.11	-9999	-0.25	42	42
MAPK3	0.024	0.014	-9999	-10000	0	0
MAPK1	0.024	0.014	-9999	-10000	0	0
NFKB1	0.014	0	-9999	-10000	0	0
MAPK8	0.006	0.086	-9999	-0.61	4	4
DUSP1	0.008	0.042	-9999	-0.31	5	5
NF-kappa-B/RelA	-0.025	0.05	-9999	-0.2	11	11
actin cytoskeleton reorganization	-0.019	0.13	-9999	-0.56	10	10
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.026	0.16	-9999	-0.53	20	20
FER	-0.025	0.13	-9999	-0.35	23	23
RELA	0.014	0	-9999	-10000	0	0
ITK	-0.048	0.13	-9999	-0.37	36	36
SOS1	0.013	0	-9999	-10000	0	0
PLCG1	-0.037	0.19	-9999	-0.57	22	22
cytokine secretion	-0.019	0.036	-9999	-0.15	7	7
SPHK1	-0.031	0.14	-9999	-0.39	22	22
PTK2	-0.021	0.14	-9999	-0.6	10	10
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.074	0.17	-9999	-0.45	32	32
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.033	0.16	-9999	-0.43	29	29
MAP2K2	0.02	0.014	-9999	-10000	0	0
MAP2K1	0.02	0.014	-9999	-10000	0	0
MAP2K7	0.014	0	-9999	-10000	0	0
KLRG1/SHP2	-0.021	0.12	-9999	-0.47	10	10
MAP2K4	0.019	0.009	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.044	0.13	-9999	-0.28	45	45
mol:Choline	-0.025	0.1	-9999	-0.25	32	32
SHC/Grb2/SOS1	-0.007	0.12	-9999	-0.49	10	10
FYN	0.014	0	-9999	-10000	0	0
DOK1	0.011	0.032	-9999	-0.37	2	2
PXN	-0.014	0.13	-9999	-0.54	10	10
HCLS1	-0.03	0.16	-9999	-0.44	23	23
PRKCB	-0.036	0.14	-9999	-0.33	38	38
FCGR2B	-0.008	0.088	-9999	-0.35	17	17
IGHE	-0.001	0.005	-9999	-10000	0	0
KLRG1/SHIP	-0.026	0.14	-9999	-0.52	15	15
LCP2	-0.015	0.11	-9999	-0.43	18	18
PLA2G4A	-0.033	0.14	-9999	-0.38	23	23
RASA1	0.009	0.045	-9999	-0.43	3	3
mol:Phosphatidic acid	-0.025	0.1	-9999	-0.25	32	32
IKK complex	-0.004	0.078	-9999	-0.2	22	22
WIPF1	-0.005	0.089	-9999	-0.43	12	12

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.031	0.1	0.34	13	-10000	0	13
GNAI2	0.014	0	-10000	0	-10000	0	0
S1P/S1P5/G12	0.003	0.056	-10000	0	-0.19	21	21
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.066	0.17	-10000	0	-0.42	52	52
RhoA/GTP	-0.031	0.11	-10000	0	-0.35	13	13
negative regulation of cAMP metabolic process	-0.041	0.12	-10000	0	-0.24	55	55
GNAZ	-0.029	0.13	-10000	0	-0.42	28	28
GNAI3	0.014	0	-10000	0	-10000	0	0
GNA12	0.014	0	-10000	0	-10000	0	0
S1PR5	-0.013	0.096	-10000	0	-0.35	21	21
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.041	0.12	-10000	0	-0.24	55	55
RhoA/GDP	0.01	0	-10000	0	-10000	0	0
RHOA	0.014	0	-10000	0	-10000	0	0
GNAI1	0.006	0.056	-10000	0	-0.4	5	5

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	-0.025	0.12	-9999	-0.28	42	42
CRKL	0.012	0.019	-9999	-0.31	1	1
Rac1/GDP	0.01	0	-9999	-10000	0	0
DOCK1	0.014	0	-9999	-10000	0	0
ITGA4	-0.038	0.14	-9999	-0.39	36	36
alpha4/beta7 Integrin/MAdCAM1	-0.019	0.1	-9999	-0.23	43	43
EPO	-0.004	0.061	-9999	-0.31	11	11
alpha4/beta7 Integrin	-0.038	0.12	-9999	-0.29	53	53
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.014	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.018	0.1	-9999	-0.27	37	37
EPO/EPOR (dimer)	0.008	0.042	-9999	-0.2	11	11
lamellipodium assembly	0.026	0.04	-9999	-0.26	5	5
PIK3CA	0.007	0.052	-9999	-0.43	4	4
PI3K	0.014	0.05	-9999	-0.35	5	5
ARF6	0.014	0	-9999	-10000	0	0
JAK2	-0.009	0.1	-9999	-0.3	25	25
PXN	0.014	0	-9999	-10000	0	0
PIK3R1	0.01	0.037	-9999	-0.43	2	2
MADCAM1	-0.002	0.064	-9999	-0.31	12	12
cell adhesion	-0.02	0.1	-9999	-0.23	43	43
CRKL/CBL	0.019	0.013	-9999	-0.2	1	1
ITGB1	0.011	0.032	-9999	-0.37	2	2
SRC	-0.02	0.11	-9999	-0.26	37	37
ITGB7	-0.017	0.11	-9999	-0.42	20	20
RAC1	0.014	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.025	0.12	-9999	-0.3	36	36
p130Cas/Crk/Dock1	0	0.097	-9999	-0.37	8	8
VCAM1	-0.022	0.12	-9999	-0.4	24	24
RHOA	0.014	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.005	0.079	-9999	-0.22	25	25
BCAR1	-0.016	0.1	-9999	-0.24	40	40
EPOR	0.014	0	-9999	-10000	0	0
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	0.026	0.041	-9999	-0.27	5	5

×

S1P1 pathway

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
VEGFR2 homodimer/VEGFA homodimer	0.007	0.053	-9999	-0.21	15	15
PDGFRB	0.008	0.046	-9999	-0.43	3	3
SPHK1	-0.029	0.11	-9999	-0.7	7	7
mol:S1P	-0.031	0.1	-9999	-0.54	9	9
S1P1/S1P/Gi	-0.06	0.16	-9999	-0.37	41	41
GNAO1	-0.068	0.17	-9999	-0.42	52	52
PDGFB-D/PDGFRB/PLCgamma1	-0.046	0.14	-9999	-0.33	40	40
PLCG1	-0.052	0.15	-9999	-0.34	41	41
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.008	0.046	-9999	-0.43	3	3
GNAI2	0.013	0.005	-9999	-10000	0	0
GNAI3	0.013	0.004	-9999	-10000	0	0
GNAI1	0.005	0.056	-9999	-0.41	5	5
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.003	0.044	-9999	-0.18	15	15
S1P1/S1P	-0.011	0.094	-9999	-0.39	10	10
negative regulation of cAMP metabolic process	-0.059	0.15	-9999	-0.36	41	41
MAPK3	-0.065	0.18	-9999	-0.46	38	38
calcium-dependent phospholipase C activity	-0.001	0.003	-9999	-10000	0	0
Rac1/GDP	0.01	0	-9999	-10000	0	0
RhoA/GDP	0.01	0	-9999	-10000	0	0
KDR	0.008	0.042	-9999	-0.34	4	4
PLCB2	-0.009	0.096	-9999	-0.36	12	12
RAC1	0.014	0	-9999	-10000	0	0
RhoA/GTP	-0.027	0.071	-9999	-0.33	10	10
receptor internalization	-0.011	0.088	-9999	-0.36	10	10
PTGS2	-0.09	0.27	-9999	-0.7	34	34
Rac1/GTP	-0.027	0.071	-9999	-0.33	10	10
RHOA	0.014	0	-9999	-10000	0	0
VEGFA	0	0.065	-9999	-0.32	11	11
negative regulation of T cell proliferation	-0.059	0.15	-9999	-0.36	41	41
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.03	0.13	-9999	-0.42	28	28
MAPK1	-0.065	0.18	-9999	-0.46	38	38
S1P1/S1P/PDGFB-D/PDGFRB	-0.008	0.097	-9999	-0.32	13	13
ABCC1	0.005	0.059	-9999	-0.43	5	5

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.01	0.052	-9999	-0.2	16	16
SNTA1	0.004	0.059	-9999	-0.36	7	7
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.008	0.057	-9999	-0.2	18	18
MAPK12	-0.006	0.092	-9999	-0.25	30	30
CCND1	0.001	0.056	-9999	-0.27	7	7
p38 gamma/SNTA1	-0.003	0.09	-9999	-0.22	33	33
MAP2K3	0.014	0	-9999	-10000	0	0
PKN1	0.01	0.037	-9999	-0.43	2	2
G2/M transition checkpoint	-0.006	0.091	-9999	-0.25	30	30
MAP2K6	0.002	0.072	-9999	-0.27	16	16
MAPT	-0.024	0.1	-9999	-0.28	34	34
MAPK13	0.004	0.063	-9999	-0.25	16	16
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.004	0.062	-9999	-0.33	8	8

×

IL2 signaling events mediated by PI3K

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
BCL2L1	-0.033	0.19	-10000	0	-0.66	18	18
UGCG	0.005	0.058	-10000	0	-0.72	1	1
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.015	0.16	-10000	0	-0.38	34	34
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.006	0.057	-10000	0	-0.71	1	1
mol:DAG	-0.024	0.14	-10000	0	-0.93	7	7
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.064	0.15	-10000	0	-0.45	36	36
FRAP1	-0.02	0.21	-10000	0	-0.52	36	36
FOXO3	-0.014	0.19	-10000	0	-0.51	32	32
AKT1	-0.022	0.21	-10000	0	-0.55	33	33
GAB2	0.012	0.027	-10000	0	-0.3	2	2
SMPD1	0.005	0.064	-10000	0	-0.87	1	1
SGMS1	-0.01	0.13	-10000	0	-0.74	7	7
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	0.012	0.043	-10000	0	-0.29	5	5
CALM1	0.014	0	-10000	0	-10000	0	0
cell proliferation	-0.002	0.11	-10000	0	-0.28	25	25
EIF3A	0.014	0	-10000	0	-10000	0	0
PI3K	0.018	0.051	-10000	0	-0.34	5	5
RPS6KB1	0.011	0.043	-10000	0	-10000	0	0
mol:sphingomyelin	-0.024	0.14	-10000	0	-0.93	7	7
natural killer cell activation	0.001	0.001	-10000	0	-10000	0	0
JAK3	-0.002	0.084	-10000	0	-0.4	12	12
PIK3R1	0.013	0.037	-10000	0	-0.43	2	2
JAK1	0.016	0.001	-10000	0	-10000	0	0
NFKB1	0.014	0	-10000	0	-10000	0	0
MYC	-0.007	0.17	-10000	0	-0.48	28	28
MYB	-0.011	0.2	-10000	0	-1	10	10
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.034	0.22	-10000	0	-0.56	36	36
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.025	0.041	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.032	0.21	-10000	0	-0.55	36	36
Rac1/GDP	0.02	0.039	-10000	0	-0.26	5	5
T cell proliferation	-0.028	0.2	-10000	0	-0.5	38	38
SHC1	0.014	0.001	-10000	0	-10000	0	0
RAC1	0.014	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.002	0.012	-10000	0	-0.051	12	12
PRKCZ	-0.031	0.21	-10000	0	-0.52	38	38
NF kappa B1 p50/RelA	-0.005	0.18	-10000	0	-0.44	36	36
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.044	0.21	-10000	0	-0.56	33	33
HSP90AA1	0.012	0.026	-10000	0	-0.43	1	1
RELA	0.014	0	-10000	0	-10000	0	0
IL2RA	-0.035	0.14	-10000	0	-0.4	33	33
IL2RB	-0.032	0.13	-10000	0	-0.38	34	34
TERT	-0.032	0.13	-10000	0	-0.39	31	31
E2F1	0.007	0.086	-10000	0	-0.43	10	10
SOS1	0.014	0.001	-10000	0	-10000	0	0
RPS6	0.014	0	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.006	0.024	12	-10000	0	12
PTPN11	0.014	0.001	-10000	0	-10000	0	0
IL2RG	-0.043	0.15	-10000	0	-0.4	40	40
actin cytoskeleton organization	-0.028	0.2	-10000	0	-0.5	38	38
GRB2	0.014	0.001	-10000	0	-10000	0	0
IL2	0.003	0.027	-10000	0	-0.3	2	2
PIK3CA	0.01	0.053	-10000	0	-0.43	4	4
Rac1/GTP	0.029	0.039	-10000	0	-0.24	5	5
LCK	-0.072	0.17	-10000	0	-0.38	63	63
BCL2	-0.015	0.21	-10000	0	-0.53	31	31

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.012	0.027	-9999	-0.3	2	2
ELF1	-0.015	0.1	-9999	-0.32	27	27
CCNA2	0.009	0.045	-9999	-0.43	3	3
PIK3CA	0.008	0.052	-9999	-0.43	4	4
JAK3	-0.003	0.084	-9999	-0.4	12	12
PIK3R1	0.011	0.037	-9999	-0.43	2	2
JAK1	0.014	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.038	0.22	-9999	-0.58	35	35
SHC1	0.014	0	-9999	-10000	0	0
SP1	0.009	0.055	-9999	-0.31	6	6
IL2RA	-0.044	0.2	-9999	-0.57	34	34
IL2RB	-0.034	0.13	-9999	-0.38	34	34
SOS1	0.014	0	-9999	-10000	0	0
IL2RG	-0.045	0.15	-9999	-0.4	40	40
G1/S transition of mitotic cell cycle	-0.007	0.14	-9999	-0.46	20	20
PTPN11	0.014	0	-9999	-10000	0	0
CCND2	0.003	0.11	-9999	-0.67	6	6
LCK	-0.074	0.17	-9999	-0.38	63	63
GRB2	0.014	0	-9999	-10000	0	0
IL2	0.002	0.027	-9999	-0.31	2	2
CDK6	-0.004	0.086	-9999	-0.43	11	11
CCND3	-0.022	0.19	-9999	-0.58	23	23

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.009	0.092	-10000	0	-0.25	24	24
ER alpha/Gai/GDP/Gbeta gamma	-0.051	0.15	-10000	0	-0.42	22	22
AKT1	-0.018	0.17	-10000	0	-0.72	15	15
PIK3CA	0.007	0.052	-10000	0	-0.43	4	4
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.021	0.18	-10000	0	-0.74	15	15
mol:Ca2+	-0.022	0.11	-10000	0	-0.38	14	14
IGF1R	0.009	0.042	-10000	0	-0.39	3	3
E2/ER alpha (dimer)/Striatin	0.001	0.068	-10000	0	-0.25	18	18
SHC1	0.014	0	-10000	0	-10000	0	0
apoptosis	0.017	0.16	0.69	15	-10000	0	15
RhoA/GTP	-0.008	0.035	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.062	0.11	-10000	0	-0.38	21	21
regulation of stress fiber formation	-0.024	0.051	0.3	2	-10000	0	2
E2/ERA-ERB (dimer)	-0.019	0.089	-10000	0	-0.2	48	48
KRAS	0.012	0.019	-10000	0	-0.31	1	1
G13/GTP	0.006	0.05	-10000	0	-0.21	14	14
pseudopodium formation	0.024	0.051	-10000	0	-0.3	2	2
E2/ER alpha (dimer)/PELP1	0.006	0.056	-10000	0	-0.24	14	14
GRB2	0.014	0	-10000	0	-10000	0	0
GNG2	-0.004	0.086	-10000	0	-0.43	11	11
GNAO1	-0.066	0.17	-10000	0	-0.42	52	52
HRAS	0.014	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.033	0.14	-10000	0	-0.45	19	19
E2/ER beta (dimer)	-0.02	0.079	-10000	0	-0.22	37	37
mol:GDP	-0.027	0.08	-10000	0	-0.34	15	15
mol:NADP	-0.033	0.14	-10000	0	-0.45	19	19
PIK3R1	0.01	0.037	-10000	0	-0.43	2	2
mol:IP3	-0.023	0.11	-10000	0	-0.4	14	14
IGF-1R heterotetramer	0.009	0.042	-10000	0	-0.39	3	3
PLCB1	-0.024	0.1	-10000	0	-0.32	17	17
PLCB2	-0.008	0.093	-10000	0	-0.39	11	11
IGF1	-0.02	0.11	-10000	0	-0.4	23	23
mol:L-citrulline	-0.033	0.14	-10000	0	-0.45	19	19
RHOA	0.014	0	-10000	0	-10000	0	0
Gai/GDP	-0.1	0.25	-10000	0	-0.64	48	48
JNK cascade	-0.02	0.079	-10000	0	-0.22	37	37
BCAR1	0.009	0.045	-10000	0	-0.43	3	3
ESR2	-0.031	0.12	-10000	0	-0.32	37	37
GNAQ	0.014	0	-10000	0	-10000	0	0
ESR1	-0.008	0.093	-10000	0	-0.41	14	14
Gq family/GDP/Gbeta gamma	0.001	0.089	-10000	0	-0.39	9	9
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.011	0.057	-10000	0	-0.26	3	3
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.06	0.11	-10000	0	-0.37	21	21
GNAZ	-0.029	0.13	-10000	0	-0.42	28	28
E2/ER alpha (dimer)	-0.005	0.065	-10000	0	-0.29	14	14
STRN	0.006	0.058	-10000	0	-0.43	5	5
GNAL	-0.074	0.16	-10000	0	-0.35	67	67
PELP1	0.014	0	-10000	0	-10000	0	0
MAPK11	-0.013	0.071	-10000	0	-0.18	41	41
GNAI2	0.014	0	-10000	0	-10000	0	0
GNAI3	0.014	0	-10000	0	-10000	0	0
GNAI1	0.006	0.056	-10000	0	-0.4	5	5
HBEGF	-0.063	0.15	-10000	0	-0.36	34	34
cAMP biosynthetic process	-0.063	0.098	-10000	0	-0.23	55	55
SRC	-0.044	0.14	-10000	0	-0.4	21	21
PI3K	0.014	0.05	-10000	0	-0.35	5	5
GNB1	0.014	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.03	0.079	-10000	0	-0.32	15	15
SOS1	0.014	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.059	0.1	-10000	0	-0.32	25	25
Gs family/GTP	-0.051	0.11	-10000	0	-0.24	55	55
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.026	0.01	-10000	0	-10000	0	0
vasodilation	-0.031	0.13	-10000	0	-0.43	19	19
mol:DAG	-0.023	0.11	-10000	0	-0.4	14	14
Gs family/GDP/Gbeta gamma	-0.055	0.093	-10000	0	-0.32	19	19
MSN	0.025	0.054	-10000	0	-0.32	2	2
Gq family/GTP	-0.008	0.079	-10000	0	-0.39	6	6
mol:PI-3-4-5-P3	-0.02	0.17	-10000	0	-0.7	15	15
NRAS	0.014	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.031	0.13	0.43	19	-10000	0	19
GRB2/SOS1	0.02	0	-10000	0	-10000	0	0
RhoA/GDP	0.001	0.084	-10000	0	-0.31	15	15
NOS3	-0.035	0.14	-10000	0	-0.48	19	19
GNA11	0.012	0.026	-10000	0	-0.43	1	1
MAPKKK cascade	-0.014	0.14	-10000	0	-0.53	15	15
E2/ER alpha (dimer)/PELP1/Src	-0.036	0.13	-10000	0	-0.39	21	21
ruffle organization	0.024	0.051	-10000	0	-0.3	2	2
ROCK2	0.022	0.054	-10000	0	-0.34	1	1
GNA14	-0.027	0.11	-10000	0	-0.32	34	34
GNA15	-0.006	0.086	-10000	0	-0.38	14	14
GNA13	0.014	0	-10000	0	-10000	0	0
MMP9	-0.071	0.16	-10000	0	-0.39	35	35
MMP2	-0.054	0.15	-10000	0	-0.42	21	21

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	-0.014	0.091	-10000	0	-0.26	33	33
MAP4K4	0.002	0.092	-10000	0	-0.41	8	8
BAG4	0.007	0.052	-10000	0	-0.43	4	4
PKC zeta/ceramide	-0.006	0.054	0.12	14	-0.23	6	20
NFKBIA	0.014	0	-10000	0	-10000	0	0
BIRC3	-0.052	0.15	-10000	0	-0.38	47	47
BAX	0.003	0.023	-10000	0	-10000	0	0
RIPK1	0.014	0	-10000	0	-10000	0	0
AKT1	0.016	0.011	-10000	0	-10000	0	0
BAD	-0.004	0.044	0.12	14	-0.1	1	15
SMPD1	0.005	0.052	-10000	0	-0.18	16	16
RB1	-0.007	0.051	0.12	14	-0.23	4	18
FADD/Caspase 8	0.01	0.091	-10000	0	-0.38	9	9
MAP2K4	-0.003	0.053	0.12	15	-0.21	7	22
NSMAF	0.014	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.002	0.041	0.12	14	-10000	0	14
EGF	-0.097	0.18	-10000	0	-0.4	76	76
mol:ceramide	-0.009	0.047	0.13	15	-10000	0	15
MADD	0.014	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.015	0.095	-10000	0	-0.27	33	33
ASAH1	0.009	0.045	-10000	0	-0.43	3	3
negative regulation of cell cycle	-0.007	0.051	0.12	14	-0.22	4	18
cell proliferation	0	0.048	-10000	0	-0.16	15	15
BID	0.005	0.07	-10000	0	-0.29	8	8
MAP3K1	-0.008	0.056	0.12	15	-0.23	7	22
EIF2A	0.007	0.041	-10000	0	-10000	0	0
TRADD	0.014	0	-10000	0	-10000	0	0
CRADD	0.011	0.027	-10000	0	-0.31	2	2
MAPK3	0.011	0.039	0.12	14	-10000	0	14
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.011	0.039	0.12	14	-10000	0	14
Cathepsin D/ceramide	-0.004	0.049	0.12	15	-0.19	4	19
FADD	0.001	0.092	-10000	0	-0.41	8	8
KSR1	-0.004	0.043	0.12	14	-0.1	1	15
MAPK8	-0.004	0.07	-10000	0	-0.28	10	10
PRKRA	-0.003	0.044	0.12	15	-10000	0	15
PDGFA	-0.03	0.12	-10000	0	-0.38	31	31
TRAF2	0.014	0	-10000	0	-10000	0	0
IGF1	-0.02	0.11	-10000	0	-0.4	23	23
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.009	0.047	0.13	15	-10000	0	15
CTSD	0.008	0.046	-10000	0	-0.37	4	4
regulation of nitric oxide biosynthetic process	0.02	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	0.009	0.059	-10000	0	-0.17	14	14
PRKCD	0.014	0	-10000	0	-10000	0	0
PRKCZ	0.003	0.069	-10000	0	-0.43	7	7
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.015	0.095	-10000	0	-0.27	33	33
RelA/NF kappa B1	0.02	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	-0.028	0.13	-10000	0	-0.42	27	27
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.004	0.097	-10000	0	-0.44	8	8
TNFR1A/BAG4/TNF-alpha	0.003	0.074	-10000	0	-0.21	29	29
mol:Sphingosine-1-phosphate	-0.014	0.091	-10000	0	-0.26	33	33
MAP2K1	0.007	0.04	0.12	14	-10000	0	14
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.014	0	-10000	0	-10000	0	0
CYCS	0.005	0.039	0.15	8	-10000	0	8
TNFRSF1A	0.014	0	-10000	0	-10000	0	0
NFKB1	0.014	0	-10000	0	-10000	0	0
TNFR1A/BAG4	0.016	0.037	-10000	0	-0.3	4	4
EIF2AK2	0.002	0.041	0.12	15	-10000	0	15
TNF-alpha/TNFR1A/FAN	0.007	0.068	-10000	0	-0.21	25	25
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.014	0.061	-10000	0	-0.24	9	9
MAP2K2	0.007	0.04	-10000	0	-10000	0	0
SMPD3	0.002	0.064	-10000	0	-0.22	17	17
TNF	-0.021	0.11	-10000	0	-0.38	25	25
PKC zeta/PAR4	-0.018	0.1	-10000	0	-0.29	34	34
mol:PHOSPHOCHOLINE	0.047	0.088	0.18	71	-10000	0	71
NF kappa B1/RelA/I kappa B alpha	0.012	0.075	-10000	0	-0.19	33	33
AIFM1	0.005	0.039	0.15	8	-10000	0	8
BCL2	0.001	0.074	-10000	0	-0.43	8	8

×

Class I PI3K 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
ARF5/GTP	0.026	0.051	0.22	7	-10000	0	7
DAPP1	-0.069	0.21	-10000	0	-0.54	35	35
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.11	0.29	-10000	0	-0.66	47	47
mol:DAG	-0.027	0.11	0.18	2	-0.26	40	42
HRAS	0.014	0.003	-10000	0	-10000	0	0
RAP1A	0.014	0.003	-10000	0	-10000	0	0
ARF5/GDP	-0.001	0.1	-10000	0	-0.28	26	26
PLCG2	-0.001	0.078	-10000	0	-0.4	10	10
PLCG1	0.014	0	-10000	0	-10000	0	0
ARF5	0.014	0	-10000	0	-10000	0	0
mol:GTP	-0.003	0.049	0.21	7	-10000	0	7
ARF1/GTP	0.024	0.053	0.21	7	-10000	0	7
RHOA	0.014	0	-10000	0	-10000	0	0
YES1	0.006	0.058	-10000	0	-0.43	5	5
RAP1A/GTP	0.018	0.05	0.2	7	-10000	0	7
ADAP1	0.011	0.06	0.2	6	-10000	0	6
ARAP3	-0.003	0.049	0.2	7	-10000	0	7
INPPL1	0.014	0	-10000	0	-10000	0	0
PREX1	0.003	0.069	-10000	0	-0.43	7	7
ARHGEF6	-0.01	0.099	-10000	0	-0.43	15	15
ARHGEF7	0.014	0	-10000	0	-10000	0	0
ARF1	0.014	0	-10000	0	-10000	0	0
NRAS	0.014	0.003	-10000	0	-10000	0	0
FYN	0.014	0	-10000	0	-10000	0	0
ARF6	0.014	0	-10000	0	-10000	0	0
FGR	-0.007	0.089	-10000	0	-0.39	14	14
mol:Ca2+	-0.008	0.058	-10000	0	-0.15	18	18
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	-0.014	0.11	-10000	0	-0.42	18	18
ZAP70	-0.07	0.16	-10000	0	-0.37	61	61
mol:IP3	-0.015	0.081	-10000	0	-0.19	33	33
LYN	0.012	0.026	-10000	0	-0.43	1	1
ARF1/GDP	-0.001	0.1	-10000	0	-0.33	18	18
RhoA/GDP	0.019	0.074	0.21	6	-0.27	7	13
PDK1/Src/Hsp90	0.026	0.023	-10000	0	-0.24	2	2
BLNK	-0.036	0.14	-10000	0	-0.41	33	33
actin cytoskeleton reorganization	0.015	0.1	0.21	6	-0.32	12	18
SRC	0.012	0.026	-10000	0	-0.43	1	1
PLEKHA2	0.009	0.061	-10000	0	-0.26	11	11
RAC1	0.014	0	-10000	0	-10000	0	0
PTEN	0.001	0.065	-10000	0	-0.4	7	7
HSP90AA1	0.012	0.026	-10000	0	-0.43	1	1
ARF6/GTP	0.027	0.049	0.22	7	-10000	0	7
RhoA/GTP	0.023	0.048	0.2	7	-10000	0	7
Src family/SYK family/BLNK-LAT	-0.11	0.28	-10000	0	-0.66	43	43
BLK	-0.085	0.17	-10000	0	-0.36	73	73
PDPK1	0.014	0	-10000	0	-10000	0	0
CYTH1	0.02	0.048	0.2	7	-10000	0	7
HCK	-0.004	0.086	-10000	0	-0.43	11	11
CYTH3	0.019	0.05	0.2	7	-10000	0	7
CYTH2	0.02	0.048	0.2	7	-10000	0	7
KRAS	0.013	0.019	-10000	0	-0.3	1	1
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.026	0.064	-10000	0	-0.38	5	5
SGK1	-0.008	0.064	0.17	7	-0.41	5	12
INPP5D	-0.009	0.095	-10000	0	-0.39	16	16
mol:GDP	-0.009	0.11	-10000	0	-0.29	27	27
SOS1	0.014	0	-10000	0	-10000	0	0
SYK	-0.011	0.099	-10000	0	-0.4	17	17
ARF6/GDP	0.018	0.074	0.22	6	-0.26	8	14
mol:PI-3-4-5-P3	-0.002	0.052	0.24	7	-10000	0	7
ARAP3/RAP1A/GTP	0.018	0.05	0.2	7	-10000	0	7
VAV1	-0.026	0.12	-10000	0	-0.42	26	26
mol:PI-3-4-P2	0.003	0.067	-10000	0	-0.27	16	16
RAS family/GTP/PI3K Class I	0.019	0.042	-10000	0	-10000	0	0
PLEKHA1	0.008	0.058	-10000	0	-0.24	12	12
Rac1/GDP	-0.001	0.1	-10000	0	-0.28	26	26
LAT	-0.021	0.11	-10000	0	-0.36	26	26
Rac1/GTP	-0.018	0.14	-10000	0	-0.39	29	29
ITK	-0.014	0.084	0.2	4	-0.33	3	7
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.045	0.16	0.2	2	-0.38	41	43
LCK	-0.075	0.17	-10000	0	-0.38	63	63
BTK	0.011	0.055	0.2	4	-10000	0	4

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.028	0.091	-10000	0	-0.22	37	37
MAPK9	0.008	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.001	0.018	-10000	0	-0.21	2	2
GNB1/GNG2	0.008	0.052	-10000	0	-0.25	11	11
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	0.008	0	-10000	0	-10000	0	0
Gs family/GTP	-0.037	0.083	-10000	0	-0.18	67	67
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	0.012	0.023	0.052	67	-10000	0	67
GNAL	-0.074	0.16	-10000	0	-0.35	67	67
GNG2	-0.004	0.086	-10000	0	-0.43	11	11
CRH	-0.001	0.026	-10000	0	-0.31	2	2
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.003	0.035	-10000	0	-0.29	4	4
MAPK11	0.003	0.035	-10000	0	-0.29	4	4

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.014	0.004	-10000	0	-10000	0	0
RAS family/GTP	-0.005	0.085	-10000	0	-0.28	10	10
NFATC4	-0.013	0.089	0.18	2	-0.29	12	14
ERBB2IP	0.009	0.045	-10000	0	-0.42	3	3
HSP90 (dimer)	0.012	0.026	-10000	0	-0.43	1	1
mammary gland morphogenesis	-0.017	0.09	0.2	2	-0.26	12	14
JUN	0.01	0.082	-10000	0	-0.25	13	13
HRAS	0.013	0.001	-10000	0	-10000	0	0
DOCK7	-0.011	0.088	0.19	3	-0.32	5	8
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.027	0.1	0.22	3	-0.23	42	45
AKT1	0.009	0.002	-10000	0	-10000	0	0
BAD	0.014	0.016	-10000	0	-0.25	1	1
MAPK10	-0.014	0.067	-10000	0	-0.19	13	13
mol:GTP	-0.001	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.016	0.098	0.21	3	-0.28	11	14
RAF1	-0.001	0.091	-10000	0	-0.3	10	10
ErbB2/ErbB3/neuregulin 2	-0.022	0.1	0.22	2	-0.26	41	43
STAT3	0.015	0.059	-10000	0	-0.96	1	1
cell migration	0	0.06	-10000	0	-0.17	9	9
mol:PI-3-4-5-P3	-0.001	0.002	-10000	0	-10000	0	0
cell proliferation	-0.042	0.23	-10000	0	-0.6	38	38
FOS	-0.007	0.15	-10000	0	-0.33	38	38
NRAS	0.013	0.001	-10000	0	-10000	0	0
mol:Ca2+	-0.017	0.09	0.2	2	-0.26	12	14
MAPK3	-0.029	0.19	-10000	0	-0.46	38	38
MAPK1	-0.029	0.19	-10000	0	-0.46	38	38
JAK2	-0.015	0.087	-10000	0	-0.32	6	6
NF2	0.002	0.007	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.02	0.09	-10000	0	-0.24	34	34
NRG1	-0.062	0.15	-10000	0	-0.35	57	57
GRB2/SOS1	0.02	0.001	-10000	0	-10000	0	0
MAPK8	-0.009	0.091	-10000	0	-0.23	35	35
MAPK9	0.005	0.05	-10000	0	-0.16	5	5
ERBB2	-0.007	0.065	0.34	3	-0.31	9	12
ERBB3	-0.007	0.093	-10000	0	-0.43	13	13
SHC1	0.013	0.001	-10000	0	-10000	0	0
RAC1	0.014	0	-10000	0	-10000	0	0
apoptosis	-0.009	0.018	0.21	1	-10000	0	1
STAT3 (dimer)	0.015	0.057	-10000	0	-0.94	1	1
RNF41	0.018	0.006	-10000	0	-10000	0	0
FRAP1	0.007	0.002	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.026	0.052	-10000	0	-0.23	5	5
ErbB2/ErbB2/HSP90 (dimer)	0.003	0.058	0.23	3	-0.28	9	12
CHRNA1	-0.054	0.24	-10000	0	-0.62	38	38
myelination	-0.012	0.085	0.18	2	-0.27	12	14
PPP3CB	-0.01	0.083	0.19	3	-0.3	5	8
KRAS	0.012	0.019	-10000	0	-0.31	1	1
RAC1-CDC42/GDP	-0.002	0.081	-10000	0	-0.24	11	11
NRG2	-0.029	0.13	-10000	0	-0.42	28	28
mol:GDP	-0.019	0.09	-10000	0	-0.24	34	34
SOS1	0.013	0.001	-10000	0	-10000	0	0
MAP2K2	-0.001	0.1	-10000	0	-0.34	8	8
SRC	0.012	0.026	-10000	0	-0.43	1	1
mol:cAMP	-0.001	0.001	-10000	0	-10000	0	0
PTPN11	-0.011	0.088	0.2	3	-0.32	5	8
MAP2K1	-0.027	0.17	-10000	0	-0.38	38	38
heart morphogenesis	-0.017	0.09	0.2	2	-0.26	12	14
RAS family/GDP	0	0.083	-10000	0	-0.26	10	10
GRB2	0.013	0.001	-10000	0	-10000	0	0
PRKACA	-0.002	0.005	-10000	0	-10000	0	0
CHRNE	0.005	0.038	-10000	0	-0.13	18	18
HSP90AA1	0.012	0.026	-10000	0	-0.43	1	1
activation of caspase activity	-0.009	0.002	-10000	0	-10000	0	0
nervous system development	-0.017	0.09	0.2	2	-0.26	12	14
CDC42	0.014	0	-10000	0	-10000	0	0

×

Cellular roles of Anthrax toxin

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
ANTXR1	-0.002	0.082	-10000	0	-0.43	10	10
ANTXR2	0	0.069	-10000	0	-0.36	10	10
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.004	0.013	-10000	0	-0.05	20	20
monocyte activation	-0.035	0.14	-10000	0	-0.44	29	29
MAP2K2	0.01	0.007	-10000	0	-10000	0	0
MAP2K1	0.005	0.013	-10000	0	-10000	0	0
MAP2K7	0.005	0.013	-10000	0	-10000	0	0
MAP2K6	-0.002	0.042	-10000	0	-0.22	9	9
CYAA	-0.003	0.052	-10000	0	-0.19	20	20
MAP2K4	0.005	0.013	-10000	0	-10000	0	0
IL1B	-0.029	0.089	-10000	0	-0.2	48	48
Channel	0.002	0.057	-10000	0	-0.2	20	20
NLRP1	-0.004	0.048	-10000	0	-0.19	15	15
CALM1	0.014	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	0.008	0.017	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.004	0.013	0.05	20	-10000	0	20
MAPK3	0.005	0.013	-10000	0	-10000	0	0
MAPK1	0.005	0.013	-10000	0	-10000	0	0
PGR	-0.006	0.046	-10000	0	-0.18	17	17
PA/Cellular Receptors	0.001	0.063	-10000	0	-0.22	20	20
apoptosis	-0.004	0.013	-10000	0	-0.05	20	20
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.003	0.053	-10000	0	-0.19	20	20
macrophage activation	0.011	0.012	-10000	0	-10000	0	0
TNF	-0.021	0.11	-10000	0	-0.38	25	25
VCAM1	-0.036	0.15	-10000	0	-0.44	29	29
platelet activation	0.008	0.017	-10000	0	-10000	0	0
MAPKKK cascade	-0.007	0.018	0.097	2	-10000	0	2
IL18	-0.02	0.089	-10000	0	-0.24	31	31
negative regulation of macrophage activation	-0.004	0.013	-10000	0	-0.05	20	20
LEF	-0.004	0.013	-10000	0	-0.051	20	20
CASP1	-0.006	0.046	-10000	0	-0.12	27	27
mol:cAMP	0.008	0.017	-10000	0	-10000	0	0
necrosis	-0.004	0.013	-10000	0	-0.05	20	20
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.003	0.053	-10000	0	-0.19	20	20
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.082	0.24	-9999	-0.73	13	13
PCK1	-0.05	0.14	-9999	-0.7	1	1
HNF4A	-0.097	0.25	-9999	-0.86	8	8
KCNJ11	-0.12	0.32	-9999	-0.85	27	27
AKT1	-0.043	0.14	-9999	-0.38	8	8
response to starvation	-0.005	0.013	-9999	-10000	0	0
DLK1	-0.1	0.27	-9999	-0.75	18	18
NKX2-1	-0.011	0.15	-9999	-10000	0	0
ACADM	-0.088	0.25	-9999	-0.76	15	15
TAT	-0.049	0.14	-9999	-0.65	4	4
CEBPB	0.007	0.015	-9999	-10000	0	0
CEBPA	-0.01	0.086	-9999	-0.38	14	14
TTR	-0.25	0.44	-9999	-1.1	50	50
PKLR	-0.21	0.38	-9999	-0.86	59	59
APOA1	-0.095	0.27	-9999	-0.98	7	7
CPT1C	-0.12	0.31	-9999	-0.84	28	28
ALAS1	-0.023	0.14	-9999	-0.51	1	1
TFRC	-0.053	0.19	-9999	-0.88	4	4
FOXF1	-0.032	0.12	-9999	-0.34	36	36
NF1	0.013	0.053	-9999	-0.42	4	4
HNF1A (dimer)	0.011	0.039	-9999	-0.43	2	2
CPT1A	-0.09	0.26	-9999	-0.79	17	17
HMGCS1	-0.089	0.25	-9999	-0.77	16	16
NR3C1	0.006	0.066	-9999	-0.43	6	6
CPT1B	-0.093	0.26	-9999	-0.79	16	16
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.013	0.011	-9999	-10000	0	0
GCK	-0.12	0.3	-9999	-0.91	20	20
CREB1	0.013	0.016	-9999	-10000	0	0
IGFBP1	-0.039	0.14	-9999	-0.65	1	1
PDX1	-0.032	0.14	-9999	-10000	0	0
UCP2	-0.092	0.26	-9999	-0.91	11	11
ALDOB	-0.085	0.26	-9999	-0.78	14	14
AFP	-0.034	0.077	-9999	-0.35	1	1
BDH1	-0.11	0.29	-9999	-0.86	23	23
HADH	-0.083	0.26	-9999	-0.8	14	14
F2	-0.095	0.27	-9999	-0.98	7	7
HNF1A	0.011	0.039	-9999	-0.43	2	2
G6PC	-0.006	0.063	-9999	-10000	0	0
SLC2A2	-0.043	0.16	-9999	-10000	0	0
INS	-0.006	0.015	-9999	-10000	0	0
FOXA1	-0.043	0.13	-9999	-0.37	36	36
FOXA3	-0.04	0.12	-9999	-0.32	43	43
FOXA2	-0.099	0.3	-9999	-0.81	19	19
ABCC8	-0.093	0.26	-9999	-0.77	15	15
ALB	-0.034	0.082	-9999	-0.35	1	1

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.016	0.005	-10000	0	-10000	0	0
PRKCZ	0.003	0.069	-10000	0	-0.43	7	7
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.014	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.012	0.089	-10000	0	-0.3	16	16
IRAK/TOLLIP	0.027	0.003	-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	-0.037	0.12	-10000	0	-0.26	56	56
IL1A	-0.024	0.099	-10000	0	-0.31	31	31
IL1B	-0.044	0.13	-10000	0	-0.29	58	58
IRAK/TRAF6/p62/Atypical PKCs	0.035	0.042	-10000	0	-10000	0	0
IL1R2	-0.033	0.13	-10000	0	-0.37	34	34
IL1R1	-0.003	0.084	-10000	0	-0.42	11	11
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.003	0.086	0.18	2	-0.29	14	16
TOLLIP	0.014	0	-10000	0	-10000	0	0
TICAM2	0	0.073	-10000	0	-0.43	8	8
MAP3K3	0.014	0	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.006	0.027	-10000	0	-0.25	3	3
IKK complex/ELKS	0.05	0.028	-10000	0	-0.32	1	1
JUN	0.023	0.046	-10000	0	-0.33	1	1
MAP3K7	0.009	0.045	-10000	0	-0.43	3	3
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.022	0.12	-10000	0	-0.43	14	14
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.004	0.08	-10000	0	-0.22	19	19
PIK3R1	0.01	0.037	-10000	0	-0.43	2	2
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.003	0.076	-10000	0	-0.2	19	19
IL1 beta fragment/IL1R1/IL1RAP	-0.035	0.13	-10000	0	-0.27	47	47
NFKB1	0.014	0	-10000	0	-10000	0	0
MAPK8	0.02	0.049	-10000	0	-0.19	9	9
IRAK1	0.021	0.003	-10000	0	-10000	0	0
IL1RN/IL1R1	-0.011	0.095	-10000	0	-0.28	30	30
IRAK4	0.012	0.019	-10000	0	-0.31	1	1
PRKCI	0.007	0.052	-10000	0	-0.43	4	4
TRAF6	0.014	0	-10000	0	-10000	0	0
PI3K	0.014	0.05	-10000	0	-0.35	5	5
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.013	0.1	-10000	0	-0.35	15	15
CHUK	0.012	0.026	-10000	0	-0.43	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.035	0.13	-10000	0	-0.27	47	47
IL1 beta/IL1R2	-0.055	0.14	-10000	0	-0.31	52	52
IRAK/TRAF6/TAK1/TAB1/TAB2	0.027	0.022	-10000	0	-0.18	3	3
NF kappa B1 p50/RelA	-0.047	0.097	-10000	0	-0.38	14	14
IRAK3	0	0.071	-10000	0	-0.37	10	10
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.024	0.13	-10000	0	-0.41	16	16
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.005	0.062	-10000	0	-0.2	18	18
IL1 alpha/IL1R1/IL1RAP	-0.014	0.086	-10000	0	-0.25	18	18
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	0.012	0.026	-10000	0	-0.43	1	1
IRAK/TRAF6/MEKK3	0.035	0.003	-10000	0	-10000	0	0
IL1RAP	-0.003	0.08	-10000	0	-0.38	12	12
UBE2N	0.014	0	-10000	0	-10000	0	0
IRAK/TRAF6	-0.044	0.091	-10000	0	-0.35	15	15
CASP1	-0.016	0.11	-10000	0	-0.4	20	20
IL1RN/IL1R2	-0.032	0.12	-10000	0	-0.28	49	49
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.025	0.12	-10000	0	-0.44	12	12
TMEM189-UBE2V1	0.008	0.007	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.012	0.069	-10000	0	-0.28	11	11
PIK3CA	0.007	0.052	-10000	0	-0.43	4	4
IL1RN	-0.015	0.1	-10000	0	-0.36	21	21
TRAF6/TAK1/TAB1/TAB2	0.022	0.022	-10000	0	-0.19	3	3
MAP2K6	0.019	0.042	-10000	0	-0.18	12	12

×

Visual signal transduction: Rods

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
mol:K +	0.014	0	-9999	-10000	0	0
GNAT1/GTP	0.003	0.013	-9999	-0.21	1	1
Metarhodopsin II/Arrestin	0.002	0.011	-9999	-0.16	1	1
PDE6G/GNAT1/GTP	-0.019	0.081	-9999	-0.22	38	38
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.003	0.02	-9999	-0.31	1	1
GRK1	0.002	0.005	-9999	-10000	0	0
CNG Channel	-0.054	0.092	-9999	-0.31	18	18
mol:Na +	-0.036	0.075	-9999	-0.29	10	10
mol:ADP	0.002	0.005	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.016	0.096	-9999	-0.26	29	29
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.019	0.086	-9999	-0.3	10	10
CNGB1	-0.008	0.071	-9999	-0.31	15	15
RDH5	-0.014	0.094	-9999	-0.33	22	22
SAG	0	0.019	-9999	-0.31	1	1
mol:Ca2+	-0.013	0.082	-9999	-0.28	10	10
Na + (4 Units)	-0.035	0.068	-9999	-0.27	10	10
RGS9	-0.038	0.13	-9999	-0.36	38	38
GNB1/GNGT1	-0.002	0.068	-9999	-0.27	17	17
GNAT1/GDP	-0.011	0.082	-9999	-0.21	29	29
GUCY2D	-0.008	0.076	-9999	-0.31	17	17
GNGT1	-0.018	0.096	-9999	-0.39	17	17
GUCY2F	0.001	0.019	-9999	-0.31	1	1
GNB5	0.009	0.045	-9999	-0.43	3	3
mol:GMP (4 units)	-0.023	0.092	-9999	-0.23	34	34
mol:11-cis-retinal	-0.014	0.094	-9999	-0.33	22	22
mol:cGMP	-0.004	0.071	-9999	-0.24	14	14
GNB1	0.014	0	-9999	-10000	0	0
Rhodopsin	-0.006	0.065	-9999	-0.23	22	22
SLC24A1	0.014	0	-9999	-10000	0	0
CNGA1	-0.019	0.098	-9999	-0.32	26	26
Metarhodopsin II	0.004	0.005	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.004	0.074	-9999	-0.26	13	13
RGS9BP	-0.004	0.084	-9999	-0.4	12	12
Metarhodopsin II/Transducin	0	0.048	-9999	-0.22	12	12
GCAP Family/Ca ++	-0.001	0.063	-9999	-0.25	13	13
PDE6A/B	-0.009	0.084	-9999	-0.25	29	29
mol:Pi	-0.016	0.096	-9999	-0.26	29	29
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	0.002	0.053	-9999	-0.22	12	12
PDE6B	-0.016	0.11	-9999	-0.4	20	20
PDE6A	0.002	0.056	-9999	-0.31	9	9
PDE6G	-0.039	0.13	-9999	-0.37	38	38
RHO	0.003	0.006	-9999	-10000	0	0
PDE6	-0.04	0.12	-9999	-0.35	18	18
GUCA1A	-0.002	0.062	-9999	-0.31	11	11
GC2/GCAP Family	-0.001	0.064	-9999	-0.25	13	13
GUCA1C	0.001	0.004	-9999	-10000	0	0
GUCA1B	-0.008	0.095	-9999	-0.42	14	14

×

Coregulation of Androgen receptor activity

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
NRIP1	0.002	0.07	-9999	-0.43	7	7
SVIL	0.008	0.046	-9999	-0.44	3	3
ZNF318	0.015	0.008	-9999	-10000	0	0
JMJD2C	-0.004	0.026	-9999	-0.069	31	31
T-DHT/AR/Ubc9	-0.023	0.087	-9999	-0.23	33	33
CARM1	0.013	0	-9999	-10000	0	0
PRDX1	0.01	0.037	-9999	-0.43	2	2
PELP1	0.014	0.001	-9999	-10000	0	0
CTNNB1	0.013	0.003	-9999	-10000	0	0
AKT1	0.014	0.002	-9999	-10000	0	0
PTK2B	0.009	0.037	-9999	-0.35	3	3
MED1	0.014	0.003	-9999	-10000	0	0
MAK	0.012	0.038	-9999	-0.43	2	2
response to oxidative stress	0	0.001	-9999	-10000	0	0
HIP1	0.013	0.003	-9999	-10000	0	0
GSN	0.011	0.027	-9999	-0.43	1	1
NCOA2	0	0.076	-9999	-0.42	9	9
NCOA6	0.013	0.003	-9999	-10000	0	0
DNA-PK	0.029	0.008	-9999	-10000	0	0
NCOA4	0.013	0	-9999	-10000	0	0
PIAS3	0.013	0.003	-9999	-10000	0	0
cell proliferation	-0.015	0.052	-9999	-0.57	2	2
XRCC5	0.014	0.002	-9999	-10000	0	0
UBE3A	0.013	0.005	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.034	0.1	-9999	-0.24	44	44
FHL2	-0.023	0.18	-9999	-0.91	10	10
RANBP9	0.013	0.003	-9999	-10000	0	0
JMJD1A	-0.018	0.053	-9999	-0.1	72	72
CDK6	-0.004	0.086	-9999	-0.43	11	11
TGFB1I1	0.001	0.072	-9999	-0.42	8	8
T-DHT/AR/CyclinD1	-0.028	0.091	-9999	-0.23	39	39
XRCC6	0.014	0.002	-9999	-10000	0	0
T-DHT/AR	-0.035	0.12	-9999	-0.29	34	34
CTDSP1	0.013	0.001	-9999	-10000	0	0
CTDSP2	0.015	0.006	-9999	-10000	0	0
BRCA1	0.01	0.038	-9999	-0.43	2	2
TCF4	-0.002	0.075	-9999	-0.34	13	13
CDKN2A	-0.14	0.2	-9999	-0.4	102	102
SRF	0.016	0.025	-9999	-10000	0	0
NKX3-1	-0.11	0.28	-9999	-0.8	33	33
KLK3	0	0.062	-9999	-10000	0	0
TMF1	0.004	0.064	-9999	-0.43	6	6
HNRNPA1	0.014	0.003	-9999	-10000	0	0
AOF2	-0.001	0.004	-9999	-10000	0	0
APPL1	0.019	0.018	-9999	-0.28	1	1
T-DHT/AR/Caspase 8	-0.024	0.089	-9999	-0.23	35	35
AR	-0.043	0.12	-9999	-0.37	32	32
UBA3	0.012	0.027	-9999	-0.43	1	1
PATZ1	0.014	0.003	-9999	-10000	0	0
PAWR	-0.029	0.13	-9999	-0.42	27	27
PRKDC	0.014	0.002	-9999	-10000	0	0
PA2G4	0.014	0.004	-9999	-10000	0	0
UBE2I	0.014	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.019	0.079	-9999	-0.2	34	34
RPS6KA3	0.011	0.027	-9999	-0.43	1	1
T-DHT/AR/ARA70	-0.023	0.087	-9999	-0.23	34	34
LATS2	0.014	0.003	-9999	-10000	0	0
T-DHT/AR/PRX1	-0.021	0.084	-9999	-0.21	35	35
Cyclin D3/CDK11 p58	0.01	0.001	-9999	-10000	0	0
VAV3	-0.024	0.11	-9999	-0.34	29	29
KLK2	-0.045	0.15	-9999	-0.69	8	8
CASP8	0.012	0.026	-9999	-0.42	1	1
T-DHT/AR/TIF2/CARM1	-0.02	0.09	-9999	-0.23	32	32
TMPRSS2	-0.079	0.22	-9999	-0.6	30	30
CCND1	0.006	0.052	-9999	-0.38	5	5
PIAS1	0.013	0.005	-9999	-10000	0	0
mol:T-DHT	-0.014	0.031	-9999	-0.068	56	56
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.011	0.027	-9999	-0.43	1	1
T-DHT/AR/CDK6	-0.033	0.1	-9999	-0.24	44	44
CMTM2	0.005	0.046	-9999	-0.3	6	6
SNURF	-0.004	0.086	-9999	-0.43	11	11
ZMIZ1	-0.001	0.039	-9999	-0.42	1	1
CCND3	0.014	0	-9999	-10000	0	0
TGIF1	0.013	0.026	-9999	-0.42	1	1
FKBP4	0.013	0.003	-9999	-10000	0	0

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.01	0.037	-9999	-0.43	2	2
SPHK1	-0.008	0.088	-9999	-0.36	16	16
GNAI2	0.014	0	-9999	-10000	0	0
mol:S1P	0.003	0.065	-9999	-0.27	13	13
GNAO1	-0.066	0.17	-9999	-0.42	52	52
mol:Sphinganine-1-P	0.002	0.066	-9999	-0.25	18	18
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.026	0.05	-9999	-0.43	1	1
GNAI3	0.014	0	-9999	-10000	0	0
G12/G13	0.02	0	-9999	-10000	0	0
S1PR3	0	0.069	-9999	-0.34	11	11
S1PR2	0.014	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	0	0.055	-9999	-0.23	13	13
S1PR5	-0.013	0.096	-9999	-0.35	21	21
S1PR4	-0.034	0.13	-9999	-0.38	34	34
GNAI1	0.006	0.056	-9999	-0.4	5	5
S1P/S1P5/G12	0.004	0.072	-9999	-0.21	19	19
S1P/S1P3/Gq	0.003	0.081	-9999	-0.34	9	9
S1P/S1P4/Gi	-0.051	0.14	-9999	-0.38	24	24
GNAQ	0.014	0	-9999	-10000	0	0
GNAZ	-0.029	0.13	-9999	-0.42	28	28
GNA14	-0.027	0.11	-9999	-0.32	34	34
GNA15	-0.006	0.086	-9999	-0.38	14	14
GNA12	0.014	0	-9999	-10000	0	0
GNA13	0.014	0	-9999	-10000	0	0
GNA11	0.012	0.026	-9999	-0.43	1	1
ABCC1	0.006	0.058	-9999	-0.43	5	5

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.014	0	-9999	-10000	0	0
VLDLR	0.001	0.071	-9999	-0.41	8	8
LRPAP1	0.014	0	-9999	-10000	0	0
NUDC	0.014	0	-9999	-10000	0	0
RELN/LRP8	-0.033	0.1	-9999	-0.19	79	79
CaM/Ca2+	0.01	0	-9999	-10000	0	0
KATNA1	0.014	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.025	0.088	-9999	-0.22	24	24
IQGAP1/CaM	0.02	0	-9999	-10000	0	0
DAB1	-0.026	0.097	-9999	-0.31	30	30
IQGAP1	0.014	0	-9999	-10000	0	0
PLA2G7	-0.034	0.13	-9999	-0.4	33	33
CALM1	0.014	0	-9999	-10000	0	0
DYNLT1	0.014	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	0.019	0.019	-9999	-0.3	1	1
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.012	0.026	-9999	-0.43	1	1
CDK5R1	0.003	0.069	-9999	-0.43	7	7
LIS1/Poliovirus Protein 3A	0.014	0	-9999	-10000	0	0
CDK5R2	-0.069	0.16	-9999	-0.37	60	60
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.061	0.12	-9999	-0.29	43	43
YWHAE	0.014	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.03	0.098	-9999	-0.3	12	12
MAP1B	-0.005	0.052	-9999	-0.26	11	11
RAC1	0.019	0	-9999	-10000	0	0
p35/CDK5	-0.015	0.087	-9999	-0.35	4	4
RELN	-0.087	0.16	-9999	-0.34	79	79
PAFAH/LIS1	-0.004	0.079	-9999	-0.24	24	24
LIS1/CLIP170	0.023	0.016	-9999	-0.24	1	1
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.04	0.06	-9999	-0.28	5	5
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.023	0.09	-9999	-0.22	34	34
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.039	0.1	-9999	-0.32	12	12
LIS1/IQGAP1	0.024	0	-9999	-10000	0	0
RHOA	0.019	0	-9999	-10000	0	0
PAFAH1B1	0.019	0	-9999	-10000	0	0
PAFAH1B3	0.012	0.026	-9999	-0.43	1	1
PAFAH1B2	0.007	0.052	-9999	-0.43	4	4
MAP1B/LIS1/Dynein heavy chain	0.015	0.035	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.024	0.096	-9999	-0.29	11	11
LRP8	0.012	0.026	-9999	-0.43	1	1
NDEL1/Katanin 60	-0.03	0.098	-9999	-0.3	12	12
P39/CDK5	-0.049	0.1	-9999	-0.3	12	12
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.024	0	-9999	-10000	0	0
CDK5	-0.018	0.082	-9999	-0.2	24	24
PPP2R5D	0.014	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.02	0.013	-9999	-0.2	1	1
CSNK2A1	0.014	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.038	0.11	-9999	-0.24	43	43
RELN/VLDLR	-0.027	0.1	-9999	-0.24	30	30
CDC42	0.019	0	-9999	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.012	0.019	-10000	0	-0.31	1	1
Rac1/GDP	0.011	0.011	-10000	0	-10000	0	0
DOCK1	0.014	0	-10000	0	-10000	0	0
ITGA4	-0.038	0.14	-10000	0	-0.39	36	36
RAC1	0.014	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	-0.038	0.12	-10000	0	-0.29	53	53
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.014	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	-0.005	0.086	-10000	0	-0.25	25	25
alpha4/beta7 Integrin/Paxillin	-0.013	0.097	-10000	0	-0.23	42	42
lamellipodium assembly	0.032	0.061	-10000	0	-0.38	5	5
PIK3CA	0.007	0.052	-10000	0	-0.43	4	4
PI3K	0.014	0.05	-10000	0	-0.35	5	5
ARF6	0.014	0	-10000	0	-10000	0	0
TLN1	0.014	0	-10000	0	-10000	0	0
PXN	0.019	0	-10000	0	-10000	0	0
PIK3R1	0.01	0.037	-10000	0	-0.43	2	2
ARF6/GTP	0.01	0.067	-10000	0	-0.37	1	1
cell adhesion	0.01	0.074	-10000	0	-0.2	25	25
CRKL/CBL	0.019	0.013	-10000	0	-0.2	1	1
alpha4/beta1 Integrin/Paxillin	0.002	0.078	-10000	0	-0.22	25	25
ITGB1	0.011	0.032	-10000	0	-0.37	2	2
ITGB7	-0.017	0.11	-10000	0	-0.42	20	20
ARF6/GDP	0.011	0.011	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.007	0.1	-10000	0	-0.24	36	36
p130Cas/Crk/Dock1	0.025	0.028	-10000	0	-0.24	3	3
VCAM1	-0.022	0.12	-10000	0	-0.4	24	24
alpha4/beta1 Integrin/Paxillin/Talin	0.011	0.075	-10000	0	-0.2	25	25
alpha4/beta1 Integrin/Paxillin/GIT1	0.011	0.075	-10000	0	-0.2	25	25
BCAR1	0.009	0.045	-10000	0	-0.43	3	3
mol:GDP	-0.01	0.074	0.2	25	-10000	0	25
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	0.011	0.075	-10000	0	-0.2	25	25
Rac1/GTP	-0.004	0.063	-10000	0	-0.42	5	5

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.011	0.031	-10000	0	-0.43	1	1
AES	0.011	0.027	-10000	0	-0.38	1	1
FBXW11	0.014	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.01	0.052	-10000	0	-0.23	12	12
SMAD4	0.014	0	-10000	0	-10000	0	0
DKK2	-0.022	0.12	-10000	0	-0.39	25	25
TLE1	0.003	0.064	-10000	0	-0.42	6	6
MACF1	0.014	0	-10000	0	-10000	0	0
CTNNB1	0.022	0.055	-10000	0	-0.24	2	2
WIF1	-0.026	0.097	-10000	0	-0.31	29	29
beta catenin/RanBP3	0.008	0.08	0.34	12	-10000	0	12
KREMEN2	-0.03	0.12	-10000	0	-0.37	32	32
DKK1	-0.11	0.18	-10000	0	-0.36	91	91
beta catenin/beta TrCP1	0.029	0.052	-10000	0	-10000	0	0
FZD1	0.002	0.064	-10000	0	-0.33	10	10
AXIN2	-0.035	0.25	-10000	0	-1.3	10	10
AXIN1	0.014	0	-10000	0	-10000	0	0
RAN	0.013	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.024	0.026	-10000	0	-0.29	1	1
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.031	0.072	-10000	0	-0.29	5	5
Axin1/APC/GSK3	0.04	0.04	0.18	1	-10000	0	1
Axin1/APC/GSK3/beta catenin/Macf1	0.032	0.051	-10000	0	-0.44	1	1
HNF1A	0.01	0.04	-10000	0	-0.43	2	2
CTBP1	0.013	0.014	-10000	0	-10000	0	0
MYC	0.009	0.047	-10000	0	-10000	0	0
RANBP3	0.013	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.021	0.11	-10000	0	-0.24	52	52
NKD1	-0.055	0.16	-10000	0	-0.4	46	46
TCF4	-0.004	0.078	-10000	0	-0.35	13	13
TCF3	0.013	0.014	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0.019	0.051	-10000	0	-0.21	4	4
Ran/GTP	0.01	0.001	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.005	0.1	0.43	10	-0.34	1	11
LEF1	-0.011	0.1	-10000	0	-0.43	15	15
DVL1	0.025	0.032	-10000	0	-0.24	3	3
CSNK2A1	0.014	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.032	0.089	-10000	0	-0.4	4	4
DKK1/LRP6/Kremen 2	-0.07	0.12	-10000	0	-0.21	116	116
LRP6	0.011	0.037	-10000	0	-0.43	2	2
CSNK1A1	0.013	0.016	-10000	0	-10000	0	0
NLK	0.014	0.003	-10000	0	-10000	0	0
CCND1	-0.004	0.14	-10000	0	-1.3	3	3
WNT1	0	0.062	-10000	0	-0.3	11	11
GSK3A	0.012	0.026	-10000	0	-0.43	1	1
GSK3B	0.014	0	-10000	0	-10000	0	0
FRAT1	0.012	0.026	-10000	0	-0.43	1	1
PPP2R5D	0.047	0.078	0.22	43	-10000	0	43
APC	0.017	0.052	-10000	0	-0.23	5	5
WNT1/LRP6/FZD1	0.026	0.042	0.2	1	-0.19	4	5
CREBBP	0.013	0.014	-10000	0	-10000	0	0

×

ErbB4 signaling events

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
ErbB4/ErbB4/HBEGF/HBEGF	0.014	0.044	-10000	0	-10000	0	0
epithelial cell differentiation	-0.042	0.07	-10000	0	-0.34	2	2
ITCH	0.018	0.01	-10000	0	-10000	0	0
WWP1	0.015	0.037	-10000	0	-10000	0	0
FYN	0.014	0	-10000	0	-10000	0	0
EGFR	-0.028	0.12	-10000	0	-0.34	33	33
PRL	-0.013	0.077	-10000	0	-0.31	18	18
neuron projection morphogenesis	0.009	0.07	-10000	0	-10000	0	0
PTPRZ1	-0.065	0.16	-10000	0	-0.41	53	53
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.003	0.077	-10000	0	-10000	0	0
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.019	0.084	-10000	0	-0.31	2	2
ADAM17	0.018	0.01	-10000	0	-10000	0	0
ErbB4/ErbB4	0.012	0.048	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.075	0.12	-10000	0	-0.35	8	8
NCOR1	0.014	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.01	0.08	-10000	0	-10000	0	0
GRIN2B	-0.017	0.084	-10000	0	-0.31	2	2
ErbB4/ErbB2/betacellulin	0.001	0.064	-10000	0	-0.29	1	1
STAT1	0.012	0.026	-10000	0	-0.43	1	1
HBEGF	0.01	0.033	-10000	0	-0.31	3	3
PRLR	-0.083	0.16	-10000	0	-0.35	74	74
E4ICDs/ETO2	-0.003	0.071	-10000	0	-0.35	1	1
axon guidance	0.024	0.066	-10000	0	-10000	0	0
NEDD4	0.013	0.047	-10000	0	-0.43	3	3
Prolactin receptor/Prolactin receptor/Prolactin	-0.065	0.12	-10000	0	-0.25	87	87
CBFA2T3	-0.02	0.11	-10000	0	-0.35	26	26
ErbB4/ErbB2/HBEGF	0.018	0.051	-10000	0	-10000	0	0
MAPK3	0.005	0.072	-10000	0	-10000	0	0
STAT1 (dimer)	0.015	0.043	-10000	0	-10000	0	0
MAPK1	0.005	0.072	-10000	0	-10000	0	0
JAK2	0.003	0.066	-10000	0	-0.41	7	7
ErbB4/ErbB2/neuregulin 1 beta	-0.019	0.086	-10000	0	-0.3	4	4
NRG1	-0.031	0.11	-10000	0	-0.24	57	57
NRG3	-0.15	0.2	-10000	0	-0.4	112	112
NRG2	-0.029	0.13	-10000	0	-0.42	28	28
NRG4	0.005	0.042	-10000	0	-0.31	5	5
heart development	0.024	0.066	-10000	0	-10000	0	0
neural crest cell migration	-0.018	0.086	-10000	0	-0.29	4	4
ERBB2	0.012	0.057	-10000	0	-0.3	9	9
WWOX/E4ICDs	0.016	0.041	-10000	0	-10000	0	0
SHC1	0.014	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.002	0.074	-10000	0	-0.33	1	1
apoptosis	0.1	0.18	0.36	83	-10000	0	83
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.008	0.086	-10000	0	-0.35	3	3
ErbB4/ErbB2/epiregulin	-0.011	0.086	-10000	0	-0.38	3	3
ErbB4/ErbB4/betacellulin/betacellulin	-0.005	0.062	-10000	0	-10000	0	0
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.028	0.1	-10000	0	-0.37	6	6
MDM2	0.013	0.046	-10000	0	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.012	0.079	-10000	0	-0.27	2	2
STAT5A	0.029	0.064	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.03	0.1	-10000	0	-0.31	12	12
DLG4	0.009	0.042	-10000	0	-0.39	3	3
GRB2/SHC	0.02	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	0.014	0.037	-10000	0	-10000	0	0
STAT5A (dimer)	-0.042	0.076	-10000	0	-0.39	1	1
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.03	0.059	-10000	0	-10000	0	0
LRIG1	0.005	0.053	-10000	0	-0.32	7	7
EREG	-0.049	0.13	-10000	0	-0.34	47	47
BTC	-0.023	0.096	-10000	0	-0.32	27	27
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.024	0.066	-10000	0	-10000	0	0
ERBB4	0.012	0.049	-10000	0	-10000	0	0
STAT5B	0.014	0	-10000	0	-10000	0	0
YAP1	0.014	0.01	-10000	0	-10000	0	0
GRB2	0.014	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0.015	0.052	-10000	0	-0.29	1	1
glial cell differentiation	-0.014	0.037	-10000	0	-10000	0	0
WWOX	0.014	0	-10000	0	-10000	0	0
cell proliferation	-0.008	0.092	-10000	0	-10000	0	0

×

Presenilin action in Notch and Wnt 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0.018	0.058	-10000	0	-0.52	2	2
HDAC1	0.009	0.027	-10000	0	-0.43	1	1
AES	0.011	0.026	-10000	0	-0.43	1	1
FBXW11	0.014	0	-10000	0	-10000	0	0
DTX1	-0.032	0.12	-10000	0	-0.36	34	34
LRP6/FZD1	0.01	0.052	-10000	0	-0.23	12	12
TLE1	0.003	0.064	-10000	0	-0.43	6	6
AP1	-0.014	0.082	-10000	0	-0.22	36	36
NCSTN	0.014	0	-10000	0	-10000	0	0
ADAM10	0.013	0	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.037	0.045	-10000	0	-10000	0	0
NICD/RBPSUH	0.027	0.046	-10000	0	-0.51	2	2
WIF1	-0.025	0.097	-10000	0	-0.31	29	29
NOTCH1	-0.004	0.046	-10000	0	-0.55	2	2
PSENEN	0.014	0	-10000	0	-10000	0	0
KREMEN2	-0.03	0.12	-10000	0	-0.37	32	32
DKK1	-0.11	0.18	-10000	0	-0.36	91	91
beta catenin/beta TrCP1	0.043	0.051	0.2	2	-10000	0	2
APH1B	0.01	0.037	-10000	0	-0.43	2	2
APH1A	0.014	0	-10000	0	-10000	0	0
AXIN1	-0.001	0.028	0.22	1	-0.23	2	3
CtBP/CBP/TCF1/TLE1/AES	0.012	0.045	-10000	0	-0.21	10	10
PSEN1	0.014	0	-10000	0	-10000	0	0
FOS	0.006	0.05	-10000	0	-0.31	7	7
JUN	0.014	0	-10000	0	-10000	0	0
MAP3K7	0.007	0.045	-10000	0	-0.43	3	3
CTNNB1	0.037	0.055	0.21	2	-10000	0	2
MAPK3	0.014	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.021	0.11	-10000	0	-0.24	52	52
HNF1A	0.01	0.037	-10000	0	-0.43	2	2
CTBP1	0.013	0.001	-10000	0	-10000	0	0
MYC	0.02	0.018	-10000	0	-10000	0	0
NKD1	-0.055	0.16	-10000	0	-0.4	46	46
FZD1	0.001	0.064	-10000	0	-0.33	10	10
NOTCH1 precursor/Deltex homolog 1	0.006	0.079	-10000	0	-0.61	2	2
apoptosis	-0.014	0.082	-10000	0	-0.22	36	36
Delta 1/NOTCHprecursor	0.02	0.058	-10000	0	-0.51	2	2
DLL1	-0.002	0.076	-10000	0	-0.36	12	12
PPARD	0.021	0.012	-10000	0	-10000	0	0
Gamma Secretase	0.039	0.02	-10000	0	-0.19	2	2
APC	-0.004	0.044	0.22	1	-0.32	4	5
DVL1	0.018	0.041	-10000	0	-0.35	3	3
CSNK2A1	0.014	0.001	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.07	0.12	-10000	0	-0.21	116	116
LRP6	0.01	0.037	-10000	0	-0.43	2	2
CSNK1A1	0.014	0.001	-10000	0	-10000	0	0
NLK	0.008	0.031	-10000	0	-0.29	3	3
CCND1	0.007	0.13	-10000	0	-1.3	3	3
WNT1	-0.001	0.062	-10000	0	-0.31	11	11
Axin1/APC/beta catenin	0.041	0.046	0.25	1	-0.29	1	2
DKK2	-0.022	0.12	-10000	0	-0.39	25	25
NOTCH1 precursor/DVL1	0.033	0.062	-10000	0	-0.6	2	2
GSK3B	0.013	0	-10000	0	-10000	0	0
FRAT1	0.011	0.026	-10000	0	-0.43	1	1
NOTCH/Deltex homolog 1	0.004	0.078	-10000	0	-0.61	2	2
PPP2R5D	0.044	0.08	0.23	41	-10000	0	41
MAPK1	0.014	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.001	0.073	-10000	0	-0.25	9	9
RBPJ	0.014	0	-10000	0	-10000	0	0
CREBBP	0.016	0.002	-10000	0	-10000	0	0

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.012	0.019	-9999	-0.31	1	1
Syndecan-3/Src/Cortactin	-0.009	0.077	-9999	-0.22	1	1
Syndecan-3/Neurocan	0.012	0.028	-9999	-10000	0	0
POMC	-0.067	0.16	-9999	-0.35	62	62
EGFR	-0.028	0.12	-9999	-0.34	33	33
Syndecan-3/EGFR	0.004	0.054	-9999	-0.19	9	9
AGRP	0.001	0.046	-9999	-0.31	6	6
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	0.01	0.037	-9999	-0.43	2	2
APH1A	0.014	0	-9999	-10000	0	0
NCAN	-0.002	0.059	-9999	-0.31	10	10
long-term memory	0.029	0.01	-9999	-10000	0	0
Syndecan-3/IL8	-0.002	0.063	-9999	-0.19	18	18
PSEN1	0.014	0	-9999	-10000	0	0
Src/Cortactin	0.018	0.023	-9999	-0.25	2	2
FYN	0.014	0	-9999	-10000	0	0
limb bud formation	0	0.004	-9999	-10000	0	0
MC4R	-0.002	0.059	-9999	-0.31	10	10
SRC	0.012	0.026	-9999	-0.43	1	1
PTN	-0.085	0.17	-9999	-0.35	76	76
FGFR/FGF/Syndecan-3	0	0.004	-9999	-10000	0	0
neuron projection morphogenesis	-0.013	0.077	-9999	-0.24	4	4
Syndecan-3/AgRP	0.01	0.023	-9999	-10000	0	0
Syndecan-3/AgRP/MC4R	0.015	0.036	-9999	-0.25	1	1
Fyn/Cortactin	0.019	0.013	-9999	-0.2	1	1
SDC3	0	0.004	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.002	0.063	-9999	-0.19	18	18
IL8	-0.039	0.13	-9999	-0.36	39	39
Syndecan-3/Fyn/Cortactin	0.03	0.01	-9999	-10000	0	0
Syndecan-3/CASK	0	0.003	-9999	-10000	0	0
alpha-MSH/MC4R	-0.047	0.12	-9999	-0.24	70	70
Gamma Secretase	0.039	0.02	-9999	-0.19	2	2

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.01	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.005	0.075	-10000	0	-0.22	21	21
regulation of S phase of mitotic cell cycle	0.007	0.06	-10000	0	-0.21	16	16
GNAO1	-0.066	0.17	-10000	0	-0.42	52	52
HRAS	0.014	0	-10000	0	-10000	0	0
SHBG/T-DHT	0.002	0.04	-10000	0	-0.22	9	9
PELP1	0.014	0	-10000	0	-10000	0	0
AKT1	0.01	0	-10000	0	-10000	0	0
MAP2K1	0.019	0.052	-10000	0	-0.21	1	1
T-DHT/AR	-0.019	0.08	-10000	0	-0.24	32	32
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-0.003	6	6
GNAI2	0.014	0	-10000	0	-10000	0	0
GNAI3	0.014	0	-10000	0	-10000	0	0
GNAI1	0.006	0.056	-10000	0	-0.4	5	5
mol:GDP	-0.023	0.071	-10000	0	-0.34	11	11
cell proliferation	0.027	0.055	-10000	0	-0.26	1	1
PIK3CA	0.007	0.052	-10000	0	-0.43	4	4
FOS	0.031	0.047	-10000	0	-10000	0	0
mol:Ca2+	-0.014	0.024	-10000	0	-0.061	39	39
MAPK3	0.023	0.053	-10000	0	-0.24	1	1
MAPK1	0.02	0.028	-10000	0	-10000	0	0
PIK3R1	0.01	0.037	-10000	0	-0.43	2	2
mol:IP3	0	0	-10000	0	-0.002	7	7
cAMP biosynthetic process	0.003	0.041	-10000	0	-0.19	9	9
GNG2	-0.004	0.086	-10000	0	-0.43	11	11
potassium channel inhibitor activity	0	0	-10000	0	-0.002	7	7
HRAS/GTP	0.008	0.056	-10000	0	-0.19	11	11
actin cytoskeleton reorganization	-0.004	0.032	-10000	0	-0.23	5	5
SRC	0.012	0.026	-10000	0	-0.43	1	1
voltage-gated calcium channel activity	0	0	-10000	0	-0.002	7	7
PI3K	0.013	0.043	-10000	0	-0.3	5	5
apoptosis	-0.028	0.042	0.22	1	-10000	0	1
T-DHT/AR/PELP1	-0.006	0.067	-10000	0	-0.19	32	32
HRAS/GDP	0.002	0.073	-10000	0	-0.32	11	11
CREB1	0.029	0.044	-10000	0	-0.23	1	1
RAC1-CDC42/GTP	0.022	0.035	-10000	0	-0.23	5	5
AR	-0.028	0.12	-10000	0	-0.34	32	32
GNB1	0.014	0	-10000	0	-10000	0	0
RAF1	0.014	0.054	-10000	0	-0.18	11	11
RAC1-CDC42/GDP	0.01	0.072	-10000	0	-0.3	11	11
T-DHT/AR/PELP1/Src	0.004	0.063	-10000	0	-0.21	12	12
MAP2K2	0.019	0.052	-10000	0	-0.21	1	1
T-DHT/AR/PELP1/Src/PI3K	0.006	0.061	-10000	0	-0.22	16	16
GNAZ	-0.029	0.13	-10000	0	-0.42	28	28
SHBG	0.001	0.069	-10000	0	-0.37	9	9
Gi family/GNB1/GNG2/GDP	-0.046	0.14	-10000	0	-0.31	49	49
mol:T-DHT	0	0	-10000	0	-10000	0	0
RAC1	0.014	0	-10000	0	-10000	0	0
GNRH1	-0.003	0.06	-10000	0	-0.29	12	12
Gi family/GTP	-0.036	0.099	-10000	0	-0.24	35	35
CDC42	0.014	0	-10000	0	-10000	0	0

×

Regulation of nuclear SMAD2/3 signaling

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
EP300	0.017	0.011	-10000	0	-10000	0	0
HSPA8	0.013	0.003	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	0.017	0.08	0.19	7	-0.26	14	21
AKT1	0.003	0.029	-10000	0	-10000	0	0
GSC	-0.03	0.23	-10000	0	-1.3	9	9
NKX2-5	-0.12	0.18	-10000	0	-0.35	101	101
muscle cell differentiation	0.029	0.067	0.32	5	-10000	0	5
SMAD2-3/SMAD4/SP1	0.028	0.086	-10000	0	-0.26	3	3
SMAD4	0.011	0.033	-10000	0	-10000	0	0
CBFB	0.014	0	-10000	0	-10000	0	0
SAP18	0.013	0.001	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.005	0.093	-10000	0	-0.21	45	45
SMAD3/SMAD4/VDR	0.046	0.046	-10000	0	-0.25	4	4
MYC	0.022	0.034	-10000	0	-0.31	1	1
CDKN2B	-0.17	0.45	-10000	0	-1.3	40	40
AP1	0.038	0.04	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.038	0.044	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.021	0.12	-10000	0	-0.3	42	42
SP3	0.01	0.046	-10000	0	-0.42	3	3
CREB1	0.014	0	-10000	0	-10000	0	0
FOXH1	0.005	0.053	-10000	0	-0.39	4	4
SMAD3/SMAD4/GR	0.022	0.06	-10000	0	-0.25	8	8
GATA3	-0.064	0.17	-10000	0	-0.42	51	51
SKI/SIN3/HDAC complex/NCoR1	0.038	0.015	-10000	0	-10000	0	0
MEF2C/TIF2	-0.042	0.12	-10000	0	-0.47	9	9
endothelial cell migration	0.024	0.2	1.2	7	-10000	0	7
MAX	0.014	0.009	-10000	0	-10000	0	0
RBBP7	0.013	0.001	-10000	0	-10000	0	0
RBBP4	0.013	0.001	-10000	0	-10000	0	0
RUNX2	-0.007	0.089	-10000	0	-0.39	14	14
RUNX3	-0.037	0.14	-10000	0	-0.43	32	32
RUNX1	0.006	0.058	-10000	0	-0.43	5	5
CTBP1	0.014	0	-10000	0	-10000	0	0
NR3C1	0.005	0.065	-10000	0	-0.43	6	6
VDR	0.007	0.052	-10000	0	-0.43	4	4
CDKN1A	0.002	0.21	-10000	0	-1.2	8	8
KAT2B	0.005	0.064	-10000	0	-0.43	6	6
SMAD2/SMAD2/SMAD4/FOXH1	0.017	0.067	-10000	0	-0.23	12	12
DCP1A	0.014	0	-10000	0	-10000	0	0
SKI	0.013	0.001	-10000	0	-10000	0	0
SERPINE1	-0.025	0.2	-10000	0	-1.3	7	7
SMAD3/SMAD4/ATF2	0.022	0.052	-10000	0	-0.23	6	6
SMAD3/SMAD4/ATF3	0.023	0.048	-10000	0	-0.23	3	3
SAP30	0.012	0.019	-10000	0	-0.31	1	1
Cbp/p300/PIAS3	0.036	0.027	0.18	1	-10000	0	1
JUN	0.034	0.039	-10000	0	-10000	0	0
SMAD3/SMAD4/IRF7	0.02	0.063	-10000	0	-0.29	6	6
TFE3	0.017	0.012	-10000	0	-10000	0	0
COL1A2	-0.034	0.17	-10000	0	-0.8	12	12
mesenchymal cell differentiation	-0.013	0.073	0.27	12	-10000	0	12
DLX1	-0.071	0.16	-10000	0	-0.38	61	61
TCF3	0.014	0	-10000	0	-10000	0	0
FOS	0.009	0.049	-10000	0	-0.3	7	7
SMAD3/SMAD4/Max	0.028	0.043	-10000	0	-0.21	2	2
Cbp/p300/SNIP1	0.03	0.01	-10000	0	-10000	0	0
ZBTB17	0.021	0.021	-10000	0	-10000	0	0
LAMC1	0.033	0.039	-10000	0	-0.27	1	1
TGIF2/HDAC complex/SMAD3/SMAD4	0.025	0.044	-10000	0	-0.22	3	3
IRF7	0.004	0.067	-10000	0	-0.41	7	7
ESR1	-0.006	0.095	-10000	0	-0.41	14	14
HNF4A	-0.002	0.052	-10000	0	-0.31	8	8
MEF2C	-0.045	0.12	-10000	0	-0.47	8	8
SMAD2-3/SMAD4	0.017	0.062	-10000	0	-0.27	2	2
Cbp/p300/Src-1	0.032	0.017	-10000	0	-10000	0	0
IGHV3OR16-13	-0.006	0.02	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.012	0.026	-10000	0	-0.43	1	1
CREBBP	0.016	0.008	-10000	0	-10000	0	0
SKIL	-0.004	0.086	-10000	0	-0.43	11	11
HDAC1	0.012	0.026	-10000	0	-0.43	1	1
HDAC2	0.013	0.001	-10000	0	-10000	0	0
SNIP1	0.013	0.002	-10000	0	-10000	0	0
GCN5L2	0.002	0.009	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.037	0.046	-10000	0	-0.23	1	1
MSG1/HSC70	-0.026	0.1	-10000	0	-0.26	45	45
SMAD2	0.002	0.035	-10000	0	-10000	0	0
SMAD3	0.011	0.045	-10000	0	-0.41	2	2
SMAD3/E2F4-5/DP1/p107/SMAD4	0.024	0.056	-10000	0	-0.24	7	7
SMAD2/SMAD2/SMAD4	0.005	0.046	-10000	0	-0.29	6	6
NCOR1	0.013	0.001	-10000	0	-10000	0	0
NCOA2	0	0.076	-10000	0	-0.42	9	9
NCOA1	0.014	0	-10000	0	-10000	0	0
MYOD/E2A	0.008	0.04	-10000	0	-0.2	10	10
SMAD2-3/SMAD4/SP1/MIZ-1	0.034	0.084	-10000	0	-0.25	2	2
IFNB1	0.018	0.056	-10000	0	-0.28	4	4
SMAD3/SMAD4/MEF2C	-0.034	0.12	-10000	0	-0.41	10	10
CITED1	-0.05	0.15	-10000	0	-0.38	45	45
SMAD2-3/SMAD4/ARC105	0.03	0.056	-10000	0	-0.27	1	1
RBL1	0.01	0.037	-10000	0	-0.43	2	2
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.031	0.18	-10000	0	-0.46	41	41
RUNX1-3/PEBPB2	-0.008	0.093	-10000	0	-0.25	36	36
SMAD7	0.046	0.074	-10000	0	-0.65	1	1
MYC/MIZ-1	0.037	0.051	0.16	34	-0.21	1	35
SMAD3/SMAD4	0.032	0.098	0.29	6	-0.4	5	11
IL10	-0.028	0.16	-10000	0	-0.52	18	18
PIASy/HDAC complex	0.01	0.028	-10000	0	-0.43	1	1
PIAS3	0.014	0.004	-10000	0	-10000	0	0
CDK2	0.001	0.078	-10000	0	-0.43	9	9
IL5	-0.022	0.12	-10000	0	-0.39	15	15
CDK4	0.014	0.029	-10000	0	-0.31	2	2
PIAS4	0.01	0.028	-10000	0	-0.43	1	1
ATF3	0.009	0.042	-10000	0	-0.34	4	4
SMAD3/SMAD4/SP1	0.026	0.07	-10000	0	-0.23	1	1
FOXG1	-0.045	0.13	-10000	0	-0.34	43	43
FOXO3	0.006	0.036	-10000	0	-10000	0	0
FOXO1	0.004	0.044	-10000	0	-0.29	2	2
FOXO4	0.006	0.036	-10000	0	-10000	0	0
heart looping	-0.045	0.12	-10000	0	-0.46	8	8
CEBPB	0.008	0.016	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.027	0.11	-10000	0	-0.25	44	44
MYOD1	-0.004	0.058	-10000	0	-0.31	10	10
SMAD3/SMAD4/HNF4	0.016	0.052	-10000	0	-0.22	4	4
SMAD3/SMAD4/GATA3	-0.025	0.14	-10000	0	-0.36	29	29
SnoN/SIN3/HDAC complex/NCoR1	-0.004	0.086	-10000	0	-0.43	11	11
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.012	0.093	-10000	0	-0.26	14	14
SMAD3/SMAD4/SP1-3	0.037	0.07	-10000	0	-10000	0	0
MED15	0.014	0	-10000	0	-10000	0	0
SP1	0.007	0.034	-10000	0	-10000	0	0
SIN3B	0.013	0.001	-10000	0	-10000	0	0
SIN3A	0.013	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.046	0.12	-10000	0	-0.3	19	19
ITGB5	0.028	0.066	-10000	0	-0.4	2	2
TGIF/SIN3/HDAC complex/CtBP	0.039	0.018	-10000	0	-0.19	1	1
SMAD3/SMAD4/AR	0.001	0.085	-10000	0	-0.25	17	17
AR	-0.028	0.12	-10000	0	-0.34	32	32
negative regulation of cell growth	0.029	0.055	-10000	0	-0.26	3	3
SMAD3/SMAD4/MYOD	0.015	0.054	-10000	0	-0.22	5	5
E2F5	-0.002	0.08	-10000	0	-0.42	10	10
E2F4	0.014	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.036	0.052	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4	-0.011	0.13	-10000	0	-0.31	42	42
TFDP1	0.014	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.043	0.044	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX2	0.014	0.074	-10000	0	-0.28	12	12
TGIF2	0.012	0.026	-10000	0	-0.43	1	1
TGIF1	0.012	0.026	-10000	0	-0.43	1	1
ATF2	0.007	0.052	-10000	0	-0.43	4	4

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.003	0.063	-9999	-0.18	29	29
RGS9BP	-0.004	0.084	-9999	-0.4	12	12
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0.002	0.005	-9999	-10000	0	0
mol:Na +	0	0.035	-9999	-0.16	12	12
mol:ADP	0.006	0.014	-9999	-0.21	1	1
GNAT2	0.013	0.003	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.016	0.096	-9999	-0.26	29	29
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0.011	0.016	-9999	-0.16	2	2
GRK7	0.007	0.02	-9999	-0.31	1	1
CNGB3	-0.005	0.055	-9999	-0.31	9	9
Cone Metarhodopsin II/X-Arrestin	0	0.018	-9999	-0.21	2	2
mol:Ca2+	-0.006	0.049	-9999	-0.29	1	1
Cone PDE6	-0.01	0.083	-9999	-0.22	20	20
Cone Metarhodopsin II	0.006	0.011	-9999	-0.15	1	1
Na + (4 Units)	-0.004	0.049	-9999	-0.17	7	7
GNAT2/GDP	-0.006	0.082	-9999	-0.21	29	29
GNB5	0.009	0.045	-9999	-0.43	3	3
mol:GMP (4 units)	0.008	0.014	-9999	-10000	0	0
Cone Transducin	0.003	0.067	-9999	-0.19	29	29
SLC24A2	-0.011	0.073	-9999	-0.31	16	16
GNB3/GNGT2	-0.009	0.087	-9999	-0.26	29	29
GNB3	-0.01	0.093	-9999	-0.37	17	17
GNAT2/GTP	0.009	0.002	-9999	-10000	0	0
CNGA3	0.003	0.033	-9999	-0.31	3	3
ARR3	0	0.026	-9999	-0.31	2	2
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	0	0.035	-9999	-0.17	12	12
mol:Pi	-0.016	0.096	-9999	-0.26	29	29
Cone CNG Channel	0.008	0.033	-9999	-0.26	1	1
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.011	0.073	-9999	-0.31	16	16
RGS9	-0.038	0.13	-9999	-0.36	38	38
PDE6C	0.002	0.005	-9999	-10000	0	0
GNGT2	-0.004	0.086	-9999	-0.41	12	12
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.002	0.027	-9999	-0.31	2	2

×

IFN-gamma 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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.014	0.089	-10000	0	-0.19	45	45
positive regulation of NF-kappaB transcription factor activity	0	0.001	-10000	0	-10000	0	0
CRKL	0.012	0.019	-10000	0	-0.31	1	1
STAT1 (dimer)/Cbp/p300	0.007	0.088	-10000	0	-0.26	8	8
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.01	0.046	-10000	0	-0.25	6	6
antigen processing and presentation of peptide antigen via MHC class I	-0.031	0.072	-10000	0	-0.25	17	17
CaM/Ca2+	-0.011	0.082	-10000	0	-0.23	4	4
RAP1A	0.014	0	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	-0.01	0.086	-10000	0	-0.26	5	5
AKT1	-0.005	0.086	-10000	0	-0.44	3	3
MAP2K1	-0.01	0.09	-10000	0	-0.3	8	8
MAP3K11	-0.013	0.082	-10000	0	-0.24	4	4
IFNGR1	0.01	0.01	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.036	0.12	-10000	0	-0.37	23	23
Rap1/GTP	-0.027	0.047	-10000	0	-0.27	1	1
CRKL/C3G	0.019	0.013	-10000	0	-0.2	1	1
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.013	0.095	-10000	0	-0.26	6	6
CEBPB	0.007	0.12	-10000	0	-0.46	12	12
STAT3	0.014	0	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.022	0.16	-10000	0	-1.1	4	4
STAT1	-0.012	0.084	-10000	0	-0.26	5	5
CALM1	0.014	0	-10000	0	-10000	0	0
IFN-gamma (dimer)	-0.083	0.17	-10000	0	-0.38	69	69
PIK3CA	0.007	0.052	-10000	0	-0.43	4	4
STAT1 (dimer)/PIAS1	-0.004	0.082	-10000	0	-0.34	2	2
CEBPB/PTGES2/Cbp/p300	-0.023	0.063	-10000	0	-0.3	9	9
mol:Ca2+	-0.015	0.087	-10000	0	-0.18	45	45
MAPK3	0	0.098	-10000	0	-0.38	8	8
STAT1 (dimer)	-0.04	0.098	-10000	0	-0.35	16	16
MAPK1	0	0.098	-10000	0	-0.38	8	8
JAK2	0	0.067	-10000	0	-0.41	7	7
PIK3R1	0.01	0.037	-10000	0	-0.43	2	2
JAK1	0.01	0.01	-10000	0	-10000	0	0
CAMK2D	0.012	0.026	-10000	0	-0.43	1	1
DAPK1	0.011	0.12	-10000	0	-0.56	9	9
SMAD7	0.007	0.053	-10000	0	-0.17	5	5
CBL/CRKL/C3G	0.001	0.078	-10000	0	-0.32	1	1
PI3K	-0.014	0.09	-10000	0	-0.41	4	4
IFNG	-0.083	0.17	-10000	0	-0.38	69	69
apoptosis	0.003	0.096	-10000	0	-0.39	11	11
CAMK2G	0.014	0	-10000	0	-10000	0	0
STAT3 (dimer)	0.014	0	-10000	0	-10000	0	0
CAMK2A	-0.048	0.14	-10000	0	-0.36	47	47
CAMK2B	-0.041	0.13	-10000	0	-0.34	43	43
FRAP1	-0.006	0.081	-10000	0	-0.41	3	3
PRKCD	-0.005	0.087	-10000	0	-0.45	3	3
RAP1B	0.012	0.019	-10000	0	-0.31	1	1
negative regulation of cell growth	-0.031	0.072	-10000	0	-0.25	17	17
PTPN2	0.012	0.026	-10000	0	-0.43	1	1
EP300	0.014	0.001	-10000	0	-10000	0	0
IRF1	0.006	0.1	-10000	0	-0.37	11	11
STAT1 (dimer)/PIASy	-0.007	0.083	0.18	2	-0.34	2	4
SOCS1	-0.002	0.16	-10000	0	-1.3	4	4
mol:GDP	-0.001	0.074	-10000	0	-0.31	1	1
CASP1	-0.002	0.079	-10000	0	-0.25	20	20
PTGES2	0.014	0	-10000	0	-10000	0	0
IRF9	0.026	0.042	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.038	0.074	-10000	0	-0.4	4	4
RAP1/GDP	-0.027	0.048	-10000	0	-0.27	1	1
CBL	-0.012	0.081	-10000	0	-0.23	4	4
MAP3K1	-0.017	0.094	-10000	0	-0.3	9	9
PIAS1	0.014	0	-10000	0	-10000	0	0
PIAS4	0.012	0.026	-10000	0	-0.43	1	1
antigen processing and presentation of peptide antigen via MHC class II	-0.031	0.072	-10000	0	-0.25	17	17
PTPN11	-0.019	0.085	-10000	0	-0.19	45	45
CREBBP	0.014	0.001	-10000	0	-10000	0	0
RAPGEF1	0.014	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class III

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
EP300	0.014	0	-10000	0	-10000	0	0
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	-0.014	0.046	0.27	6	-10000	0	6
CDKN1A	-0.016	0.1	-10000	0	-0.63	8	8
KAT2B	0.004	0.064	-10000	0	-0.43	6	6
BAX	0.014	0	-10000	0	-10000	0	0
FOXO3	0.001	0.011	-10000	0	-10000	0	0
FOXO1	0.01	0.037	-10000	0	-0.43	2	2
FOXO4	0.019	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.014	0	-10000	0	-10000	0	0
TAT	0.002	0.033	-10000	0	-0.31	3	3
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0	0.062	-10000	0	-0.25	15	15
PPARGC1A	-0.11	0.2	-10000	0	-0.41	83	83
FHL2	-0.002	0.082	-10000	0	-0.43	10	10
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.016	0.043	-10000	0	-0.3	4	4
HIST2H4A	0.014	0.046	-10000	0	-0.27	6	6
SIRT1/FOXO3a	0.002	0.036	-10000	0	-0.25	4	4
SIRT1	0.007	0.06	0.19	7	-0.44	4	11
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.024	0.037	-10000	0	-0.25	4	4
SIRT1/Histone H1b	0.015	0.048	0.15	6	-0.22	9	15
apoptosis	-0.023	0.037	0.25	4	-10000	0	4
SIRT1/PGC1A	-0.06	0.12	-10000	0	-0.24	87	87
p53/SIRT1	0.001	0.076	0.37	7	-0.3	7	14
SIRT1/FOXO4	0.02	0.037	0.15	7	-0.24	4	11
FOXO1/FHL2/SIRT1	0.012	0.061	-10000	0	-0.23	14	14
HIST1H1E	0.013	0.039	-10000	0	-0.24	6	6
SIRT1/p300	0.016	0.043	-10000	0	-0.3	4	4
muscle cell differentiation	-0.006	0.07	0.33	8	-10000	0	8
TP53	0.008	0.056	0.19	7	-0.39	4	11
KU70/SIRT1/BAX	0.024	0.037	-10000	0	-0.25	4	4
CREBBP	0.014	0	-10000	0	-10000	0	0
MEF2D	0.014	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.007	0.048	-10000	0	-0.26	7	7
ACSS2	0.014	0.05	-10000	0	-0.32	5	5
SIRT1/PCAF/MYOD	0.007	0.071	-10000	0	-0.33	8	8

×

Atypical NF-kappaB 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.018	0.027	-9999	-0.3	2	2
FBXW11	0.014	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.022	0.022	-9999	-0.24	2	2
NF kappa B1 p50/RelA/I kappa B alpha	-0.002	0.1	-9999	-0.37	13	13
NFKBIA	-0.024	0.11	-9999	-0.26	41	41
MAPK14	0.014	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.024	0	-9999	-10000	0	0
ARRB2	0.015	0	-9999	-10000	0	0
REL	0.01	0.037	-9999	-0.43	2	2
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.022	0.022	-9999	-0.24	2	2
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.024	0	-9999	-10000	0	0
PIK3CA	0.007	0.052	-9999	-0.43	4	4
NF kappa B1 p50 dimer	0.018	0	-9999	-10000	0	0
PIK3R1	0.01	0.037	-9999	-0.43	2	2
NFKB1	0.019	0	-9999	-10000	0	0
RELA	0.014	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	-0.015	0.098	-9999	-0.23	41	41
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.002	0.097	-9999	-0.36	13	13
SRC	0.012	0.026	-9999	-0.43	1	1
PI3K	0.014	0.05	-9999	-0.35	5	5
NF kappa B1 p50/RelA	-0.015	0.099	-9999	-0.24	41	41
IKBKB	0.014	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.014	0	-9999	-10000	0	0
SYK	-0.011	0.099	-9999	-0.4	17	17
I kappa B alpha/PIK3R1	-0.017	0.11	-9999	-0.38	15	15
cell death	0.002	0.093	-9999	-0.34	13	13
NF kappa B1 p105/c-Rel	0.022	0.022	-9999	-0.24	2	2
LCK	-0.075	0.17	-9999	-0.38	63	63
BCL3	0.01	0.037	-9999	-0.43	2	2

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	0.018	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	-0.001	0.078	-9999	-0.43	9	9
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.014	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.014	0.024	-9999	-0.18	1	1
response to UV	0	0	-9999	-10000	0	0
YES1	0.006	0.058	-9999	-0.43	5	5
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	-0.007	0.089	-9999	-0.39	14	14
p38 alpha/TAB1	-0.041	0.082	-9999	-0.26	26	26
PRKG1	-0.017	0.1	-9999	-0.37	22	22
DUSP8	-0.012	0.098	-9999	-0.38	18	18
PGK/cGMP/p38 alpha	-0.046	0.086	-9999	-0.24	31	31
apoptosis	-0.039	0.079	-9999	-0.25	26	26
RAL/GTP	0.018	0	-9999	-10000	0	0
LYN	0.012	0.026	-9999	-0.43	1	1
DUSP1	0.008	0.042	-9999	-0.31	5	5
PAK1	0.01	0.037	-9999	-0.35	3	3
SRC	0.012	0.026	-9999	-0.43	1	1
RAC1/OSM/MEKK3/MKK3	0.035	0	-9999	-10000	0	0
TRAF6	0.014	0	-9999	-10000	0	0
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	0.014	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0.018	0	-9999	-10000	0	0
MAPK11	-0.026	0.12	-9999	-0.32	30	30
BLK	-0.085	0.17	-9999	-0.36	73	73
HCK	-0.004	0.086	-9999	-0.43	11	11
MAP2K3	0.014	0	-9999	-10000	0	0
DUSP16	0.014	0	-9999	-10000	0	0
DUSP10	0.004	0.064	-9999	-0.43	6	6
TRAF6/MEKK3	0.017	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	-0.014	0.1	-9999	-0.28	24	24
positive regulation of innate immune response	-0.025	0.14	-9999	-0.35	28	28
LCK	-0.075	0.17	-9999	-0.38	63	63
p38alpha-beta/MKP7	-0.017	0.13	-9999	-0.34	26	26
p38alpha-beta/MKP5	-0.02	0.14	-9999	-0.34	29	29
PGK/cGMP	-0.011	0.074	-9999	-0.26	22	22
PAK2	0.014	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.019	0.13	-9999	-0.34	26	26
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	-0.019	0.092	-9999	-0.31	26	26

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.014	0	-10000	0	-10000	0	0
PTK2	0.014	0	-10000	0	-10000	0	0
CRKL	-0.002	0.068	-10000	0	-0.21	20	20
GRB2/SOS1/SHC	0.028	0	-10000	0	-10000	0	0
HRAS	0.014	0	-10000	0	-10000	0	0
IRS1/Crk	-0.001	0.068	-10000	0	-0.21	20	20
IGF-1R heterotetramer/IGF1/PTP1B	0.002	0.07	-10000	0	-0.23	21	21
AKT1	0.009	0.067	-10000	0	-0.3	4	4
BAD	0.013	0.065	-10000	0	-0.32	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.002	0.067	-10000	0	-0.21	20	20
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0	0.068	-10000	0	-0.21	20	20
RAF1	0.02	0.062	-10000	0	-0.3	3	3
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.01	0.066	-10000	0	-0.2	20	20
YWHAZ	0.014	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.007	0.074	-10000	0	-0.2	31	31
PIK3CA	0.007	0.052	-10000	0	-0.43	4	4
RPS6KB1	0.009	0.067	-10000	0	-0.34	3	3
GNB2L1	0.014	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	0.015	0.055	-10000	0	-0.26	3	3
PXN	0.014	0	-10000	0	-10000	0	0
PIK3R1	0.01	0.037	-10000	0	-0.43	2	2
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.02	0	-10000	0	-10000	0	0
HRAS/GTP	-0.017	0.047	-10000	0	-0.25	2	2
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.022	0.056	-10000	0	-0.17	19	19
IGF-1R heterotetramer	0.003	0.045	-10000	0	-0.39	3	3
IGF-1R heterotetramer/IGF1/IRS/Nck	0.002	0.069	-10000	0	-0.21	20	20
Crk/p130 Cas/Paxillin	0.012	0.067	-10000	0	-0.24	5	5
IGF1R	0.003	0.045	-10000	0	-0.39	3	3
IGF1	-0.022	0.12	-10000	0	-0.41	23	23
IRS2/Crk	0.005	0.065	-10000	0	-0.2	21	21
PI3K	0.005	0.076	-10000	0	-0.21	24	24
apoptosis	-0.02	0.059	0.28	3	-10000	0	3
HRAS/GDP	0.01	0	-10000	0	-10000	0	0
PRKCD	0.007	0.085	-10000	0	-0.3	19	19
RAF1/14-3-3 E	0.026	0.057	-10000	0	-0.26	3	3
BAD/14-3-3	0.02	0.062	-10000	0	-0.29	3	3
PRKCZ	0.004	0.073	-10000	0	-0.3	4	4
Crk/p130 Cas/Paxillin/FAK1	-0.017	0.047	-10000	0	-0.27	4	4
PTPN1	0.012	0.019	-10000	0	-0.31	1	1
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.002	0.089	-10000	0	-0.32	19	19
BCAR1	0.009	0.045	-10000	0	-0.43	3	3
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.009	0.069	-10000	0	-0.2	25	25
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.014	0	-10000	0	-10000	0	0
IRS1/NCK2	0	0.068	-10000	0	-0.21	20	20
GRB10	0.004	0.064	-10000	0	-0.43	6	6
PTPN11	-0.002	0.067	-10000	0	-0.21	20	20
IRS1	-0.009	0.073	-10000	0	-0.2	31	31
IRS2	-0.003	0.068	-10000	0	-0.21	21	21
IGF-1R heterotetramer/IGF1	-0.011	0.089	-10000	0	-0.28	26	26
GRB2	0.014	0	-10000	0	-10000	0	0
PDPK1	0.005	0.07	-10000	0	-0.2	24	24
YWHAE	0.014	0	-10000	0	-10000	0	0
PRKD1	0.007	0.085	-10000	0	-0.3	19	19
SHC1	0.014	0	-10000	0	-10000	0	0

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.012	0.019	-10000	0	-0.31	1	1
mol:Halofuginone	0.004	0.006	-10000	0	-10000	0	0
ITGA1	-0.002	0.076	-10000	0	-0.36	12	12
CDKN1A	0.013	0.072	-10000	0	-0.39	8	8
PRL-3/alpha Tubulin	0.015	0.04	-10000	0	-0.28	5	5
mol:Ca2+	-0.079	0.13	0.34	3	-0.25	93	96
AGT	-0.11	0.18	-10000	0	-0.36	94	94
CCNA2	0.022	0.043	-10000	0	-10000	0	0
TUBA1B	0.014	0	-10000	0	-10000	0	0
EGR1	0.01	0.048	-10000	0	-0.21	12	12
CDK2/Cyclin E1	0.019	0.075	-10000	0	-0.34	8	8
MAPK3	0.014	0.039	-10000	0	-0.28	5	5
PRL-2 /Rab GGTase beta	0.02	0	-10000	0	-10000	0	0
MAPK1	0.014	0.039	-10000	0	-0.28	5	5
PTP4A1	0.02	0.04	-10000	0	-10000	0	0
PTP4A3	0.006	0.056	-10000	0	-0.4	5	5
PTP4A2	0.014	0	-10000	0	-10000	0	0
ITGB1	0.012	0.045	-10000	0	-0.27	7	7
SRC	0.012	0.026	-10000	0	-0.43	1	1
RAC1	0.019	0.054	-10000	0	-0.39	4	4
Rab GGTase beta/Rab GGTase alpha	0.02	0	-10000	0	-10000	0	0
PRL-1/ATF-5	0.026	0.037	-10000	0	-10000	0	0
RABGGTA	0.014	0	-10000	0	-10000	0	0
BCAR1	0.002	0.044	0.34	3	-0.31	2	5
RHOC	0.019	0.054	-10000	0	-0.39	4	4
RHOA	0.019	0.054	-10000	0	-0.39	4	4
cell motility	0.019	0.059	-10000	0	-0.39	4	4
PRL-1/alpha Tubulin	0.026	0.037	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	0.004	0.066	-10000	0	-0.25	17	17
ROCK1	0.019	0.06	-10000	0	-0.39	4	4
RABGGTB	0.014	0	-10000	0	-10000	0	0
CDK2	-0.001	0.078	-10000	0	-0.43	9	9
mitosis	0.02	0.04	-10000	0	-10000	0	0
ATF5	0.014	0	-10000	0	-10000	0	0

×

Regulation of Androgen receptor activity

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
HDAC1	0.018	0.019	-9999	-0.3	1	1
SMARCC1	0.008	0.01	-9999	-10000	0	0
REL	0.011	0.037	-9999	-0.43	2	2
HDAC7	-0.002	0.096	-9999	-0.31	7	7
JUN	0.013	0.001	-9999	-10000	0	0
EP300	0.013	0	-9999	-10000	0	0
KAT2B	0.004	0.064	-9999	-0.43	6	6
KAT5	0.014	0	-9999	-10000	0	0
MAPK14	0.004	0.058	-9999	-0.31	9	9
FOXO1	0.01	0.037	-9999	-0.43	2	2
T-DHT/AR	-0.001	0.1	-9999	-0.32	6	6
MAP2K6	-0.003	0.079	-9999	-0.44	9	9
BRM/BAF57	0.02	0.004	-9999	-10000	0	0
MAP2K4	0.011	0.007	-9999	-10000	0	0
SMARCA2	0.013	0.001	-9999	-10000	0	0
PDE9A	-0.1	0.31	-9999	-0.99	29	29
NCOA2	0	0.076	-9999	-0.42	9	9
CEBPA	-0.006	0.086	-9999	-0.38	14	14
EHMT2	0.013	0.001	-9999	-10000	0	0
cell proliferation	0.002	0.12	-9999	-0.34	11	11
NR0B1	-0.097	0.17	-9999	-0.38	77	77
EGR1	-0.001	0.069	-9999	-0.33	12	12
RXRs/9cRA	-0.03	0.1	-9999	-0.22	65	65
AR/RACK1/Src	0.006	0.072	-9999	-0.27	7	7
AR/GR	0	0.074	-9999	-0.24	17	17
GNB2L1	0.013	0.001	-9999	-10000	0	0
PKN1	0.01	0.037	-9999	-0.43	2	2
RCHY1	0.01	0.037	-9999	-0.43	2	2
epidermal growth factor receptor activity	0	0.002	-9999	-10000	0	0
MAPK8	0.01	0.039	-9999	-0.3	4	4
T-DHT/AR/TIF2/CARM1	0.005	0.085	-9999	-0.3	12	12
SRC	0.008	0.056	-9999	-0.22	9	9
NR3C1	0.004	0.064	-9999	-0.43	6	6
KLK3	-0.054	0.1	-9999	-0.38	6	6
APPBP2	0.011	0.007	-9999	-10000	0	0
TRIM24	0.013	0.002	-9999	-10000	0	0
T-DHT/AR/TIP60	0.005	0.067	-9999	-0.24	13	13
TMPRSS2	-0.061	0.24	-9999	-0.82	20	20
RXRG	-0.088	0.18	-9999	-0.43	65	65
mol:9cRA	0	0.001	-9999	-10000	0	0
RXRA	0.013	0	-9999	-10000	0	0
RXRB	0.013	0	-9999	-10000	0	0
CARM1	0.013	0.002	-9999	-10000	0	0
NR2C2	0.01	0.037	-9999	-0.43	2	2
KLK2	-0.012	0.13	-9999	-0.46	13	13
AR	-0.001	0.069	-9999	-0.22	16	16
SENP1	0.013	0	-9999	-10000	0	0
HSP90AA1	0.012	0.026	-9999	-0.43	1	1
MDM2	0.009	0.042	-9999	-0.33	4	4
SRY	-0.002	0.037	-9999	-0.31	4	4
GATA2	-0.004	0.082	-9999	-0.37	13	13
MYST2	0.014	0	-9999	-10000	0	0
HOXB13	-0.14	0.2	-9999	-0.41	98	98
T-DHT/AR/RACK1/Src	0.008	0.069	-9999	-0.26	7	7
positive regulation of transcription	-0.004	0.082	-9999	-0.37	13	13
DNAJA1	0.011	0.007	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.02	0.035	-9999	-0.28	3	3
NCOA1	0.017	0.003	-9999	-10000	0	0
SPDEF	0.002	0.053	-9999	-0.31	8	8
T-DHT/AR/TIF2	0.01	0.093	-9999	-0.42	8	8
T-DHT/AR/Hsp90	0.004	0.069	-9999	-0.24	14	14
GSK3B	0.013	0.002	-9999	-10000	0	0
NR2C1	0.014	0.001	-9999	-10000	0	0
mol:T-DHT	0.005	0.059	-9999	-0.23	13	13
SIRT1	0.007	0.052	-9999	-0.43	4	4
ZMIZ2	0.014	0.003	-9999	-10000	0	0
POU2F1	0.007	0.037	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.049	0.1	-9999	-0.26	29	29
CREBBP	0.013	0	-9999	-10000	0	0
SMARCE1	0.013	0.001	-9999	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.002	0.1	-10000	0	-0.31	16	16
BAG4	0.007	0.052	-10000	0	-0.43	4	4
BAD	0.011	0.038	-10000	0	-0.13	10	10
NFKBIA	0.014	0	-10000	0	-10000	0	0
BIRC3	-0.052	0.15	-10000	0	-0.38	47	47
BAX	0.012	0.037	-10000	0	-0.12	9	9
EnzymeConsortium:3.1.4.12	0.003	0.026	-10000	0	-0.078	15	15
IKBKB	0.007	0.096	-10000	0	-0.35	9	9
MAP2K2	0.02	0.037	-10000	0	-0.21	1	1
MAP2K1	0.02	0.037	-10000	0	-0.21	1	1
SMPD1	0.007	0.03	-10000	0	-0.11	9	9
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.008	0.099	-10000	0	-0.34	10	10
MAP2K4	0.012	0.05	-10000	0	-0.2	8	8
protein ubiquitination	0.008	0.098	-10000	0	-0.34	11	11
EnzymeConsortium:2.7.1.37	0.022	0.041	-10000	0	-0.21	1	1
response to UV	0	0	-10000	0	-0.001	9	9
RAF1	0.016	0.039	-10000	0	-0.19	2	2
CRADD	0.011	0.027	-10000	0	-0.31	2	2
mol:ceramide	0.007	0.038	-10000	0	-0.13	10	10
I-kappa-B-alpha/RELA/p50/ubiquitin	0.018	0	-10000	0	-10000	0	0
MADD	0.014	0	-10000	0	-10000	0	0
MAP3K1	0.007	0.052	-10000	0	-0.17	16	16
TRADD	0.014	0	-10000	0	-10000	0	0
RELA/p50	0.014	0	-10000	0	-10000	0	0
MAPK3	0.023	0.037	-10000	0	-0.2	1	1
MAPK1	0.023	0.037	-10000	0	-0.2	1	1
p50/RELA/I-kappa-B-alpha	0.02	0	-10000	0	-10000	0	0
FADD	0.002	0.1	-10000	0	-0.31	16	16
KSR1	0.011	0.04	-10000	0	-0.14	10	10
MAPK8	0.014	0.06	-10000	0	-0.26	8	8
TRAF2	0.014	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	0.007	0.098	-10000	0	-0.35	10	10
TNF R/SODD	0.016	0.037	-10000	0	-0.3	4	4
TNF	-0.021	0.11	-10000	0	-0.38	25	25
CYCS	0.015	0.039	0.12	6	-0.12	9	15
IKBKG	0.007	0.096	-10000	0	-0.35	9	9
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.004	0.1	-10000	0	-0.29	29	29
RELA	0.014	0	-10000	0	-10000	0	0
RIPK1	0.014	0	-10000	0	-10000	0	0
AIFM1	0.015	0.039	0.12	6	-0.12	9	15
TNF/TNF R/SODD	0.003	0.074	-10000	0	-0.21	29	29
TNFRSF1A	0.014	0	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.016	0.042	-10000	0	-0.52	1	1
NSMAF	0.002	0.099	-10000	0	-0.3	16	16
response to hydrogen peroxide	0	0	-10000	0	-0.001	9	9
BCL2	0.001	0.074	-10000	0	-0.43	8	8

×

Retinoic acid receptors-mediated 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
HDAC1	0.012	0.026	-10000	0	-0.43	1	1
HDAC3	0.014	0	-10000	0	-10000	0	0
VDR	0.007	0.052	-10000	0	-0.43	4	4
Cbp/p300/PCAF	0.022	0.039	-10000	0	-0.24	6	6
EP300	0.014	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.014	0.071	-10000	0	-0.33	5	5
KAT2B	0.004	0.064	-10000	0	-0.43	6	6
MAPK14	0.014	0	-10000	0	-10000	0	0
AKT1	0.009	0.08	0.19	9	-0.23	21	30
RAR alpha/9cRA/Cyclin H	0	0.073	-10000	0	-0.32	10	10
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.008	0.082	-10000	0	-0.32	8	8
CDC2	0	0.002	-10000	0	-10000	0	0
response to UV	0.001	0.003	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.007	0.071	-10000	0	-0.51	4	4
NCOR2	0.012	0.026	-10000	0	-0.43	1	1
VDR/VDR/Vit D3	0.006	0.037	-10000	0	-0.3	4	4
RXRs/RARs/NRIP1/9cRA	-0.014	0.16	-10000	0	-0.59	15	15
NCOA2	0	0.076	-10000	0	-0.42	9	9
NCOA3	0.014	0	-10000	0	-10000	0	0
NCOA1	0.014	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.007	0.052	-10000	0	-0.43	4	4
RARG	0.014	0.002	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.019	0.002	-10000	0	-10000	0	0
MAPK3	0.014	0.002	-10000	0	-10000	0	0
MAPK1	0.014	0	-10000	0	-10000	0	0
MAPK8	0.008	0.054	-10000	0	-0.44	4	4
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.005	0.11	-10000	0	-0.41	15	15
RARA	0.009	0.066	-10000	0	-0.28	11	11
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.002	0.1	-10000	0	-0.44	8	8
PRKCA	-0.002	0.085	-10000	0	-0.4	12	12
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.027	0.17	-10000	0	-0.63	15	15
RXRG	-0.06	0.14	-10000	0	-0.28	72	72
RXRA	0.013	0.065	-10000	0	-0.26	11	11
RXRB	0.008	0.059	-10000	0	-0.28	10	10
VDR/Vit D3/DNA	0.006	0.037	-10000	0	-0.3	4	4
RBP1	-0.038	0.13	-10000	0	-0.35	40	40
CRBP1/9-cic-RA	-0.026	0.089	-10000	0	-0.24	40	40
RARB	-0.028	0.13	-10000	0	-0.41	29	29
PRKCG	0.001	0.053	-10000	0	-0.3	8	8
MNAT1	0.014	0	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.004	0.14	-10000	0	-0.52	15	15
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.002	0.12	-10000	0	-0.41	15	15
proteasomal ubiquitin-dependent protein catabolic process	0.011	0.089	-10000	0	-0.42	6	6
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.027	0.17	-10000	0	-0.63	15	15
positive regulation of DNA binding	-0.014	0.063	-10000	0	-0.3	10	10
NRIP1	-0.035	0.22	-10000	0	-1.1	9	9
RXRs/RARs	-0.029	0.16	-10000	0	-0.48	22	22
RXRs/RXRs/DNA/9cRA	-0.01	0.11	-10000	0	-0.44	14	14
PRKACA	0.014	0	-10000	0	-10000	0	0
CDK7	0.014	0	-10000	0	-10000	0	0
TFIIH	0.028	0	-10000	0	-10000	0	0
RAR alpha/9cRA	0.028	0.047	-10000	0	-0.32	3	3
CCNH	0.014	0	-10000	0	-10000	0	0
CREBBP	0.014	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	0	0	-10000	0	-10000	0	0

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.021	0.12	-10000	0	-0.39	24	24
HRAS	0.014	0	-10000	0	-10000	0	0
EGFR	-0.028	0.12	-10000	0	-0.34	33	33
AKT	0.026	0.028	-10000	0	-0.18	1	1
FOXO3	0.014	0	-10000	0	-10000	0	0
AKT1	0.014	0	-10000	0	-10000	0	0
FOXO1	0.01	0.037	-10000	0	-0.43	2	2
AKT3	0.012	0.026	-10000	0	-0.43	1	1
FOXO4	0.014	0	-10000	0	-10000	0	0
MET	-0.051	0.15	-10000	0	-0.4	44	44
PIK3CA	0.007	0.052	-10000	0	-0.43	4	4
PIK3CB	0.014	0	-10000	0	-10000	0	0
NRAS	0.014	0	-10000	0	-10000	0	0
PIK3CG	-0.042	0.14	-10000	0	-0.38	40	40
PIK3R3	0.014	0	-10000	0	-10000	0	0
PIK3R2	0.014	0	-10000	0	-10000	0	0
NF1	0.007	0.052	-10000	0	-0.43	4	4
RAS	-0.018	0.079	0.18	3	-0.26	12	15
ERBB2	-0.001	0.078	-10000	0	-0.43	9	9
proliferation/survival/translation	-0.013	0.049	0.3	2	-10000	0	2
PI3K	-0.02	0.089	0.16	4	-0.24	24	28
PIK3R1	0.01	0.037	-10000	0	-0.43	2	2
KRAS	0.012	0.019	-10000	0	-0.31	1	1
FOXO	0.033	0.028	0.15	4	-10000	0	4
AKT2	0.014	0	-10000	0	-10000	0	0
PTEN	0.003	0.069	-10000	0	-0.43	7	7

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.08	0.31	-9999	-1	24	24
RAD9A	0.014	0	-9999	-10000	0	0
AP1	0.014	0.036	-9999	-0.2	7	7
IFNAR2	0.013	0.007	-9999	-10000	0	0
AKT1	0.004	0.043	-9999	-0.2	3	3
ER alpha/Oestrogen	-0.005	0.066	-9999	-0.29	14	14
NFX1/SIN3/HDAC complex	0.036	0.019	-9999	-10000	0	0
EGF	-0.098	0.18	-9999	-0.4	76	76
SMG5	0.014	0	-9999	-10000	0	0
SMG6	0.014	0	-9999	-10000	0	0
SP3/HDAC2	0.016	0.034	-9999	-0.29	3	3
TERT/c-Abl	-0.069	0.29	-9999	-0.99	23	23
SAP18	0.013	0.002	-9999	-10000	0	0
MRN complex	0.017	0.062	-9999	-0.33	8	8
WT1	-0.062	0.15	-9999	-0.38	52	52
WRN	0.007	0.052	-9999	-0.43	4	4
SP1	0.013	0.01	-9999	-10000	0	0
SP3	0.008	0.045	-9999	-0.43	3	3
TERF2IP	0.014	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.084	0.24	-9999	-0.87	23	23
Mad/Max	0.02	0.008	-9999	-10000	0	0
TERT	-0.085	0.32	-9999	-1.1	23	23
CCND1	-0.068	0.28	-9999	-0.95	25	25
MAX	0.013	0.004	-9999	-10000	0	0
RBBP7	0.013	0.002	-9999	-10000	0	0
RBBP4	0.013	0.002	-9999	-10000	0	0
TERF2	0.014	0.009	-9999	-10000	0	0
PTGES3	0.014	0	-9999	-10000	0	0
SIN3A	0.013	0.002	-9999	-10000	0	0
Telomerase/911	0.027	0.035	-9999	-10000	0	0
CDKN1B	-0.031	0.11	-9999	-0.25	16	16
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	0.019	-9999	-0.31	1	1
TRF2/PARP2	0.021	0.007	-9999	-10000	0	0
UBE3A	0.013	0.004	-9999	-10000	0	0
JUN	0.013	0.004	-9999	-10000	0	0
E6	-0.001	0.004	-9999	-10000	0	0
HPV-16 E6/E6AP	0.01	0.007	-9999	-10000	0	0
FOS	0.005	0.05	-9999	-0.31	7	7
IFN-gamma/IRF1	-0.047	0.13	-9999	-0.29	49	49
PARP2	0.014	0	-9999	-10000	0	0
BLM	0.01	0.037	-9999	-0.43	2	2
Telomerase	0.018	0.07	-9999	-0.36	6	6
IRF1	0.007	0.061	-9999	-0.37	7	7
ESR1	-0.008	0.093	-9999	-0.41	14	14
KU/TER	0.02	0	-9999	-10000	0	0
ATM/TRF2	0.016	0.039	-9999	-0.27	5	5
ubiquitin-dependent protein catabolic process	0.041	0.018	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.041	0.018	-9999	-10000	0	0
HDAC1	0.012	0.026	-9999	-0.43	1	1
HDAC2	0.012	0.01	-9999	-10000	0	0
ATM	-0.006	0.047	-9999	-0.36	5	5
SMAD3	0.012	0.049	-9999	-0.3	7	7
ABL1	0.014	0	-9999	-10000	0	0
MXD1	0.013	0.004	-9999	-10000	0	0
MRE11A	0.009	0.045	-9999	-0.43	3	3
HUS1	0.014	0	-9999	-10000	0	0
RPS6KB1	0.014	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.054	0.28	-9999	-0.96	23	23
NR2F2	0.013	0.028	-9999	-0.43	1	1
MAPK3	0.01	0.019	-9999	-0.2	2	2
MAPK1	0.01	0.019	-9999	-0.2	2	2
TGFB1/TGF beta receptor Type II	0.006	0.058	-9999	-0.43	5	5
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	-0.006	0.047	-9999	-0.36	5	5
NBN	0.01	0.037	-9999	-0.43	2	2
EGFR	-0.028	0.12	-9999	-0.34	33	33
mol:Oestrogen	0	0.003	-9999	-10000	0	0
EGF/EGFR	-0.086	0.15	-9999	-0.28	99	99
MYC	0.012	0.02	-9999	-0.31	1	1
IL2	0	0.029	-9999	-0.3	2	2
KU	0.02	0	-9999	-10000	0	0
RAD50	0.004	0.064	-9999	-0.43	6	6
HSP90AA1	0.012	0.026	-9999	-0.43	1	1
TGFB1	0.006	0.059	-9999	-0.43	5	5
TRF2/BLM	0.019	0.026	-9999	-0.27	2	2
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.061	0.29	-9999	-0.98	23	23
SP1/HDAC2	0.02	0.017	-9999	-10000	0	0
PINX1	0.011	0.032	-9999	-0.37	2	2
Telomerase/EST1A	-0.084	0.24	-9999	-0.87	23	23
Smad3/Myc	0.018	0.043	-9999	-0.23	8	8
911 complex	0.028	0	-9999	-10000	0	0
IFNG	-0.08	0.17	-9999	-0.37	69	69
Telomerase/PinX1	-0.084	0.24	-9999	-0.87	23	23
Telomerase/AKT1/mTOR/p70S6K	0.012	0.063	-9999	-0.26	2	2
SIN3B	0.013	0.002	-9999	-10000	0	0
YWHAE	0.014	0	-9999	-10000	0	0
Telomerase/EST1B	-0.084	0.24	-9999	-0.87	23	23
response to DNA damage stimulus	0.001	0.017	-9999	-0.13	5	5
MRN complex/TRF2/Rap1	0.031	0.052	-9999	-0.29	6	6
TRF2/WRN	0.016	0.034	-9999	-0.26	4	4
Telomerase/hnRNP C1/C2	-0.084	0.24	-9999	-0.87	23	23
E2F1	0.01	0.038	-9999	-0.43	2	2
ZNFX1	0.013	0.002	-9999	-10000	0	0
PIF1	0.006	0.058	-9999	-0.43	5	5
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

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.009	0.045	-9999	-0.43	3	3
mol:S1P	0.001	0.002	-9999	-10000	0	0
S1P1/S1P/Gi	-0.03	0.11	-9999	-0.25	29	29
GNAO1	-0.065	0.17	-9999	-0.42	52	52
S1P/S1P3/G12/G13	0.021	0.037	-9999	-0.16	11	11
AKT1	-0.001	0.072	-9999	-0.52	3	3
AKT3	-0.001	0.098	-9999	-0.74	2	2
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.009	0.045	-9999	-0.43	3	3
GNAI2	0.015	0.002	-9999	-10000	0	0
GNAI3	0.015	0.002	-9999	-10000	0	0
GNAI1	0.007	0.056	-9999	-0.4	5	5
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.001	0.069	-9999	-0.34	11	11
S1PR2	0.014	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	-0.028	0.11	-9999	-0.35	11	11
MAPK3	-0.021	0.11	-9999	-0.34	10	10
MAPK1	-0.021	0.11	-9999	-0.34	10	10
JAK2	-0.027	0.11	-9999	-0.34	11	11
CXCR4	-0.029	0.11	-9999	-0.35	11	11
FLT1	0.012	0.042	-9999	-0.39	3	3
RhoA/GDP	0.01	0	-9999	-10000	0	0
Rac1/GDP	0.01	0	-9999	-10000	0	0
SRC	-0.022	0.11	-9999	-0.34	10	10
S1P/S1P3/Gi	-0.028	0.11	-9999	-0.36	11	11
RAC1	0.014	0	-9999	-10000	0	0
RhoA/GTP	-0.019	0.1	-9999	-0.33	10	10
VEGFA	0.003	0.065	-9999	-0.32	11	11
S1P/S1P2/Gi	-0.026	0.11	-9999	-0.38	8	8
VEGFR1 homodimer/VEGFA homodimer	0.015	0.056	-9999	-0.23	13	13
RHOA	0.014	0	-9999	-10000	0	0
S1P/S1P3/Gq	0.001	0.07	-9999	-0.24	15	15
GNAQ	0.014	0	-9999	-10000	0	0
GNAZ	-0.028	0.13	-9999	-0.42	28	28
G12/G13	0.02	0	-9999	-10000	0	0
GNA14	-0.027	0.11	-9999	-0.32	34	34
GNA15	-0.006	0.086	-9999	-0.38	14	14
GNA12	0.014	0	-9999	-10000	0	0
GNA13	0.014	0	-9999	-10000	0	0
GNA11	0.012	0.026	-9999	-0.43	1	1
Rac1/GTP	-0.019	0.1	-9999	-0.33	10	10

×

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	-0.078	0.16	-9999	-0.35	71	71
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.012	0.026	-9999	-0.43	1	1
TCEB1	0.014	0	-9999	-10000	0	0
HIF1A/p53	0.02	0.04	-9999	-0.32	2	2
HIF1A	0.016	0.031	-9999	-0.3	2	2
COPS5	0.014	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.037	0.028	-9999	-0.19	4	4
FIH (dimer)	0.012	0.026	-9999	-0.43	1	1
CDKN2A	-0.14	0.2	-9999	-0.4	102	102
ARNT/IPAS	-0.043	0.11	-9999	-0.23	71	71
HIF1AN	0.012	0.026	-9999	-0.43	1	1
GNB2L1	0.014	0	-9999	-10000	0	0
HIF1A/ARNT	0.023	0.03	-9999	-0.39	1	1
CUL2	0.009	0.045	-9999	-0.43	3	3
OS9	0.012	0.019	-9999	-0.31	1	1
RACK1/Elongin B/Elongin C	0.027	0.016	-9999	-0.24	1	1
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.023	0.033	-9999	-0.39	1	1
PHD1-3/OS9	0.026	0.043	-9999	-0.21	6	6
HIF1A/RACK1/Elongin B/Elongin C	0.034	0.031	-9999	-0.36	1	1
VHL	0.014	0	-9999	-10000	0	0
HSP90AA1	0.012	0.026	-9999	-0.43	1	1
HIF1A/JAB1	0.023	0.03	-9999	-0.39	1	1
EGLN3	-0.002	0.076	-9999	-0.37	11	11
EGLN2	0.014	0	-9999	-10000	0	0
EGLN1	0.014	0	-9999	-10000	0	0
TP53	0.007	0.052	-9999	-0.43	4	4
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.031	0.025	-9999	-10000	0	0
ARNT	0.014	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.014	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.045	0.098	-9999	-0.42	2	2

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	0.13	0.28	-9999	-0.93	8	8
PLK1	0.052	0.12	-9999	-1.3	2	2
BIRC5	0.048	0.15	-9999	-1.3	3	3
HSPA1B	0.13	0.29	-9999	-0.97	8	8
MAP2K1	0.039	0.028	-9999	-10000	0	0
BRCA2	0.11	0.34	-9999	-1.1	14	14
FOXM1	0.12	0.36	-9999	-1.3	8	8
XRCC1	0.13	0.28	-9999	-1	6	6
FOXM1B/p19	-0.081	0.22	-9999	-0.99	9	9
Cyclin D1/CDK4	0.071	0.32	-9999	-0.91	10	10
CDC2	0.13	0.29	-9999	-0.99	8	8
TGFA	0.051	0.34	-9999	-0.93	12	12
SKP2	0.13	0.29	-9999	-1.1	6	6
CCNE1	0.017	0.019	-9999	-0.29	1	1
CKS1B	0.13	0.28	-9999	-1.1	5	5
RB1	-0.061	0.16	-9999	-0.8	9	9
FOXM1C/SP1	0.12	0.3	-9999	-1.1	8	8
AURKB	0.043	0.17	-9999	-1.3	4	4
CENPF	0.13	0.3	-9999	-1.1	7	7
CDK4	0.018	0.029	-9999	-0.29	2	2
MYC	0.13	0.26	-9999	-0.87	6	6
CHEK2	0.039	0.028	-9999	-10000	0	0
ONECUT1	0.071	0.34	-9999	-0.95	10	10
CDKN2A	-0.14	0.2	-9999	-0.4	102	102
LAMA4	0.12	0.32	-9999	-1.1	10	10
FOXM1B/HNF6	0.065	0.37	-9999	-1.1	10	10
FOS	0.13	0.28	-9999	-1	6	6
SP1	0.015	0.001	-9999	-10000	0	0
CDC25B	0.13	0.28	-9999	-1	6	6
response to radiation	0.021	0.026	-9999	-10000	0	0
CENPB	0.13	0.28	-9999	-1	6	6
CENPA	0.12	0.3	-9999	-1.2	7	7
NEK2	0.13	0.3	-9999	-1.1	6	6
HIST1H2BA	0.12	0.28	-9999	-1	6	6
CCNA2	0.014	0.048	-9999	-0.44	3	3
EP300	0.014	0	-9999	-10000	0	0
CCNB1/CDK1	0.12	0.31	-9999	-1.2	6	6
CCNB2	0.12	0.3	-9999	-1	8	8
CCNB1	0.13	0.29	-9999	-1.1	6	6
ETV5	0.12	0.29	-9999	-0.99	8	8
ESR1	0.1	0.35	-9999	-1.1	15	15
CCND1	0.074	0.33	-9999	-0.94	10	10
GSK3A	0.033	0.038	-9999	-0.44	1	1
Cyclin A-E1/CDK1-2	0.039	0.069	-9999	-0.26	11	11
CDK2	0.004	0.078	-9999	-0.43	9	9
G2/M transition of mitotic cell cycle	0.026	0.029	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.044	0.22	-9999	-1	8	8
GAS1	0.12	0.32	-9999	-1.1	11	11
MMP2	0.078	0.39	-9999	-1	24	24
RB1/FOXM1C	0.074	0.33	-9999	-1	8	8
CREBBP	0.014	0	-9999	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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	0.012	0.026	-9999	-0.43	1	1
HDAC2	0.013	0	-9999	-10000	0	0
GNB1/GNG2	-0.017	0.1	-9999	-0.24	47	47
forebrain development	-0.025	0.14	-9999	-0.48	16	16
GNAO1	-0.066	0.17	-9999	-0.42	52	52
SMO/beta Arrestin2	-0.019	0.11	-9999	-0.3	36	36
SMO	-0.042	0.15	-9999	-0.43	36	36
ARRB2	0.014	0.002	-9999	-10000	0	0
GLI3/SPOP	0.045	0.074	-9999	-0.68	1	1
mol:GTP	0	0.001	-9999	-10000	0	0
GSK3B	0.014	0	-9999	-10000	0	0
GNAI2	0.014	0.001	-9999	-10000	0	0
SIN3/HDAC complex	0.034	0.01	-9999	-10000	0	0
GNAI1	0.006	0.056	-9999	-0.41	5	5
XPO1	0.015	0.003	-9999	-10000	0	0
GLI1/Su(fu)	-0.027	0.14	-9999	-0.43	15	15
SAP30	0.012	0.019	-9999	-0.31	1	1
mol:GDP	-0.042	0.15	-9999	-0.43	36	36
MIM/GLI2A	-0.001	0.076	-9999	-0.37	11	11
IFT88	0.01	0.037	-9999	-0.43	2	2
GNAI3	0.014	0.001	-9999	-10000	0	0
GLI2	0.027	0.04	-9999	-10000	0	0
GLI3	0.039	0.078	-9999	-0.72	1	1
CSNK1D	0.014	0	-9999	-10000	0	0
CSNK1E	0.014	0	-9999	-10000	0	0
SAP18	0.013	0	-9999	-10000	0	0
embryonic digit morphogenesis	0.01	0.037	-9999	-0.43	2	2
GNG2	-0.004	0.086	-9999	-0.43	11	11
Gi family/GTP	-0.061	0.15	-9999	-0.45	20	20
SIN3B	0.013	0	-9999	-10000	0	0
SIN3A	0.013	0	-9999	-10000	0	0
GLI3/Su(fu)	0.047	0.055	-9999	-0.56	1	1
GLI2/Su(fu)	0.025	0.062	-9999	-0.24	4	4
FOXA2	-0.027	0.11	-9999	-0.72	6	6
neural tube patterning	-0.025	0.14	-9999	-0.48	16	16
SPOP	0.014	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.01	0.056	-9999	-10000	0	0
GNB1	0.014	0	-9999	-10000	0	0
CSNK1G2	0.009	0.045	-9999	-0.43	3	3
CSNK1G3	0.006	0.058	-9999	-0.43	5	5
MTSS1	-0.001	0.076	-9999	-0.37	11	11
embryonic limb morphogenesis	-0.025	0.14	-9999	-0.48	16	16
SUFU	0.002	0.061	-9999	-10000	0	0
LGALS3	-0.006	0.091	-9999	-0.42	13	13
catabolic process	0.055	0.072	-9999	-0.64	1	1
GLI3A/CBP	0.004	0.069	-9999	-0.31	11	11
KIF3A	0.01	0.037	-9999	-0.43	2	2
GLI1	-0.026	0.14	-9999	-0.49	16	16
RAB23	0.014	0	-9999	-10000	0	0
CSNK1A1	0.014	0	-9999	-10000	0	0
IFT172	-0.002	0.082	-9999	-0.43	10	10
RBBP7	0.013	0	-9999	-10000	0	0
Su(fu)/Galectin3	-0.001	0.074	-9999	-0.23	13	13
GNAZ	-0.029	0.13	-9999	-0.42	28	28
RBBP4	0.013	0	-9999	-10000	0	0
CSNK1G1	0.014	0	-9999	-10000	0	0
PIAS1	0.014	0	-9999	-10000	0	0
PRKACA	0.014	0	-9999	-10000	0	0
GLI2/SPOP	0.033	0.038	-9999	-10000	0	0
STK36	0.015	0.003	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.054	0.14	-9999	-0.42	20	20
PTCH1	-0.025	0.17	-9999	-0.91	7	7
MIM/GLI1	-0.026	0.14	-9999	-0.47	17	17
CREBBP	0.004	0.069	-9999	-0.31	11	11
Su(fu)/SIN3/HDAC complex	0.035	0.025	-9999	-0.24	1	1

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.014	0	-10000	0	-10000	0	0
NFATC1	0.034	0.061	-10000	0	-0.25	8	8
NFATC2	0.013	0.055	-10000	0	-0.26	4	4
NFATC3	0.013	0.054	-10000	0	-0.33	7	7
YWHAE	0.014	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.028	0.12	-10000	0	-0.35	23	23
Exportin 1/Ran/NUP214	0.028	0.001	-10000	0	-10000	0	0
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.039	0.14	-10000	0	-0.36	33	33
BCL2/BAX	0.011	0.052	-10000	0	-0.3	8	8
CaM/Ca2+/Calcineurin A alpha-beta B1	0.011	0.002	-10000	0	-10000	0	0
CaM/Ca2+	0.011	0.002	-10000	0	-10000	0	0
BAX	0.014	0	-10000	0	-10000	0	0
MAPK14	0.014	0.001	-10000	0	-10000	0	0
BAD	0.012	0.026	-10000	0	-0.43	1	1
CABIN1/MEF2D	-0.02	0.11	-10000	0	-0.35	21	21
Calcineurin A alpha-beta B1/BCL2	0.001	0.073	-10000	0	-0.43	8	8
FKBP8	0.012	0.026	-10000	0	-0.43	1	1
activation-induced cell death of T cells	0.02	0.11	0.34	21	-10000	0	21
KPNB1	0.014	0	-10000	0	-10000	0	0
KPNA2	0.014	0	-10000	0	-10000	0	0
XPO1	0.014	0	-10000	0	-10000	0	0
SFN	-0.08	0.15	-10000	0	-0.33	77	77
MAP3K8	-0.004	0.08	-10000	0	-0.36	13	13
NFAT4/CK1 alpha	0.021	0.045	-10000	0	-0.19	8	8
MEF2D/NFAT1/Cbp/p300	0.039	0.059	-10000	0	-0.28	4	4
CABIN1	-0.029	0.12	-10000	0	-0.35	23	23
CALM1	0.014	0.001	-10000	0	-10000	0	0
RAN	0.014	0	-10000	0	-10000	0	0
MAP3K1	0.003	0.069	-10000	0	-0.43	7	7
CAMK4	-0.059	0.16	-10000	0	-0.39	51	51
mol:Ca2+	0.001	0.002	-10000	0	-10000	0	0
MAPK3	0.014	0	-10000	0	-10000	0	0
YWHAH	0.014	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.008	0.083	-10000	0	-0.24	31	31
YWHAB	0.014	0	-10000	0	-10000	0	0
MAPK8	0.008	0.052	-10000	0	-0.43	4	4
MAPK9	0.014	0	-10000	0	-10000	0	0
YWHAG	0.014	0	-10000	0	-10000	0	0
FKBP1A	0.012	0.019	-10000	0	-0.31	1	1
NFAT1-c-4/YWHAQ	0.044	0.066	-10000	0	-0.25	7	7
PRKCH	0.01	0.037	-10000	0	-0.43	2	2
CABIN1/Cbp/p300	0.021	0.003	-10000	0	-10000	0	0
CASP3	0.014	0.001	-10000	0	-10000	0	0
PIM1	0.014	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.009	0.011	-10000	0	-0.17	1	1
apoptosis	-0.003	0.024	0.19	1	-0.27	1	2
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.014	0.045	-10000	0	-0.21	1	1
PRKCB	-0.049	0.15	-10000	0	-0.38	44	44
PRKCE	0.014	0	-10000	0	-10000	0	0
JNK2/NFAT4	0.019	0.049	-10000	0	-0.29	7	7
BAD/BCL-XL	0.019	0.019	-10000	0	-0.3	1	1
PRKCD	0.014	0	-10000	0	-10000	0	0
NUP214	0.014	0	-10000	0	-10000	0	0
PRKCZ	0.003	0.069	-10000	0	-0.43	7	7
PRKCA	-0.004	0.084	-10000	0	-0.4	12	12
PRKCG	-0.001	0.053	-10000	0	-0.31	8	8
PRKCQ	-0.062	0.16	-10000	0	-0.4	52	52
FKBP38/BCL2	0.01	0.056	-10000	0	-0.3	9	9
EP300	0.014	0.002	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.014	0	-10000	0	-10000	0	0
NFATc/JNK1	0.038	0.063	-10000	0	-0.25	1	1
CaM/Ca2+/FKBP38	0.018	0.016	-10000	0	-0.25	1	1
FKBP12/FK506	0.009	0.013	-10000	0	-0.21	1	1
CSNK1A1	0.017	0.003	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.024	0.094	-10000	0	-0.22	51	51
NFATc/ERK1	0.041	0.058	-10000	0	-0.25	1	1
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.04	0.14	-10000	0	-0.36	33	33
NR4A1	0.035	0.068	-10000	0	-0.37	5	5
GSK3B	0.014	0.001	-10000	0	-10000	0	0
positive T cell selection	0.013	0.054	-10000	0	-0.32	7	7
NFAT1/CK1 alpha	0.015	0.043	-10000	0	-0.23	3	3
RCH1/ KPNB1	0.02	0	-10000	0	-10000	0	0
YWHAQ	0.014	0	-10000	0	-10000	0	0
PRKACA	0.014	0.001	-10000	0	-10000	0	0
AKAP5	-0.027	0.12	-10000	0	-0.36	31	31
MEF2D	0.014	0.002	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.014	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.041	0.058	-10000	0	-0.25	1	1
CREBBP	0.014	0.002	-10000	0	-10000	0	0
BCL2	0.001	0.074	-10000	0	-0.43	8	8

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.023	0.16	-10000	0	-0.59	2	2
CRP	0.018	0.16	-10000	0	-0.64	2	2
cell cycle arrest	0.015	0.17	-10000	0	-0.52	8	8
TIMP1	0.029	0.16	-10000	0	-0.69	4	4
IL6ST	-0.015	0.11	-10000	0	-0.42	20	20
Rac1/GDP	0.001	0.12	-10000	0	-0.35	15	15
AP1	0.052	0.059	-10000	0	-0.35	1	1
GAB2	0.013	0.027	-10000	0	-0.3	2	2
TNFSF11	-0.046	0.32	-10000	0	-0.96	27	27
HSP90B1	0.033	0.036	-10000	0	-10000	0	0
GAB1	0.012	0.037	-10000	0	-0.43	2	2
MAPK14	0.003	0.12	-10000	0	-0.51	9	9
AKT1	0.045	0.052	-10000	0	-0.63	1	1
FOXO1	0.047	0.055	-10000	0	-0.49	2	2
MAP2K6	0.001	0.11	0.22	1	-0.36	12	13
mol:GTP	0	0.002	-10000	0	-10000	0	0
MAP2K4	0.012	0.13	-10000	0	-0.38	11	11
MITF	-0.013	0.12	0.23	1	-0.33	15	16
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	-0.039	0.25	-10000	0	-1.3	11	11
CEBPB	0.02	0.002	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.029	0.057	0.23	4	-0.28	1	5
STAT3	0.014	0.17	-10000	0	-0.55	8	8
STAT1	-0.002	0.052	-10000	0	-0.86	1	1
CEBPD	0.016	0.18	-10000	0	-0.77	5	5
PIK3CA	0.009	0.052	-10000	0	-0.43	4	4
PI3K	0.016	0.051	-10000	0	-0.35	5	5
JUN	0.014	0	-10000	0	-10000	0	0
PIAS3/MITF	-0.007	0.11	0.22	1	-0.33	12	13
MAPK11	0	0.12	-10000	0	-0.5	10	10
STAT3 (dimer)/FOXO1	0.044	0.16	-10000	0	-0.47	9	9
GRB2/SOS1/GAB family	0.013	0.097	0.19	4	-0.34	8	12
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.004	0.11	-10000	0	-0.34	14	14
GRB2	0.015	0.003	-10000	0	-10000	0	0
JAK2	0.003	0.066	-10000	0	-0.41	7	7
LBP	0.026	0.14	-10000	0	-0.48	2	2
PIK3R1	0.011	0.037	-10000	0	-0.43	2	2
JAK1	0.015	0.006	-10000	0	-10000	0	0
MYC	0.023	0.16	-10000	0	-0.56	3	3
FGG	0.015	0.16	-10000	0	-0.64	2	2
macrophage differentiation	0.015	0.17	-10000	0	-0.52	8	8
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0	0.11	-10000	0	-0.35	14	14
JUNB	0.022	0.15	-10000	0	-0.57	2	2
FOS	0.006	0.05	-10000	0	-0.31	7	7
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	0.006	0.1	0.24	1	-0.38	7	8
STAT1/PIAS1	0.017	0.1	0.25	1	-0.32	7	8
GRB2/SOS1/GAB family/SHP2/PI3K	0.037	0.055	-10000	0	-0.34	4	4
STAT3 (dimer)	0.014	0.17	-10000	0	-0.54	8	8
PRKCD	0.02	0.14	-10000	0	-0.41	11	11
IL6R	0.004	0.07	-10000	0	-0.43	7	7
SOCS3	-0.009	0.18	-10000	0	-1	7	7
gp130 (dimer)/JAK1/JAK1/LMO4	0.013	0.076	-10000	0	-0.23	23	23
Rac1/GTP	0.003	0.12	-10000	0	-0.35	15	15
HCK	-0.004	0.086	-10000	0	-0.43	11	11
MAPKKK cascade	0.041	0.054	-10000	0	-0.4	1	1
bone resorption	-0.039	0.3	-10000	0	-0.89	27	27
IRF1	0.014	0.19	-10000	0	-0.88	5	5
mol:GDP	-0.005	0.12	-10000	0	-0.35	17	17
SOS1	0.015	0.005	-10000	0	-10000	0	0
VAV1	-0.006	0.12	-10000	0	-0.35	17	17
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.003	0.12	-10000	0	-0.41	16	16
PTPN11	0.004	0.014	-10000	0	-10000	0	0
IL6/IL6RA	-0.006	0.091	-10000	0	-0.25	31	31
gp130 (dimer)/TYK2/TYK2/LMO4	0.01	0.074	-10000	0	-0.24	23	23
gp130 (dimer)/JAK2/JAK2/LMO4	0.004	0.096	-10000	0	-0.3	23	23
IL6	-0.016	0.1	-10000	0	-0.35	25	25
PIAS3	0.014	0	-10000	0	-10000	0	0
PTPRE	-0.005	0.074	-10000	0	-0.41	9	9
PIAS1	0.014	0	-10000	0	-10000	0	0
RAC1	0.014	0.001	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.001	0.093	0.22	1	-0.28	11	12
LMO4	0.012	0.047	-10000	0	-0.43	3	3
STAT3 (dimer)/PIAS3	0.018	0.17	-10000	0	-0.54	6	6
MCL1	0.05	0.047	-10000	0	-0.55	1	1

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.016	0.078	-9999	-0.3	13	13
STMN1	0.013	0.051	-9999	-0.35	5	5
Aurora B/RasGAP/Survivin	0.02	0.056	-9999	-0.28	9	9
Chromosomal passenger complex/Cul3 protein complex	-0.022	0.094	-9999	-0.19	54	54
BIRC5	0.009	0.048	-9999	-0.45	3	3
DES	-0.074	0.2	-9999	-0.59	34	34
Aurora C/Aurora B/INCENP	0.01	0.058	-9999	-0.18	24	24
Aurora B/TACC1	0.016	0.032	-9999	-0.25	4	4
Aurora B/PP2A	0.017	0.038	-9999	-0.3	4	4
mol:GTP	0	0	-9999	-10000	0	0
CBX5	0.012	0.018	-9999	-0.14	4	4
mitotic metaphase/anaphase transition	0	0.002	-9999	-10000	0	0
NDC80	0.012	0.054	-9999	-0.34	6	6
Cul3 protein complex	-0.044	0.12	-9999	-0.22	82	82
KIF2C	0.012	0.08	-9999	-0.42	6	6
PEBP1	0.014	0.002	-9999	-10000	0	0
KIF20A	0.01	0.037	-9999	-0.43	2	2
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	0.013	0.05	-9999	-0.3	7	7
SEPT1	-0.02	0.11	-9999	-0.35	26	26
SMC2	0.01	0.037	-9999	-0.43	2	2
SMC4	0.004	0.064	-9999	-0.43	6	6
NSUN2/NPM1/Nucleolin	0.016	0.09	-9999	-0.72	4	4
PSMA3	0.014	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0	0.001	-9999	-10000	0	0
H3F3B	0.011	0.036	-9999	-0.29	4	4
AURKB	0.009	0.054	-9999	-0.44	4	4
AURKC	-0.012	0.093	-9999	-0.34	20	20
CDCA8	0.009	0.048	-9999	-0.45	3	3
cytokinesis	0.017	0.1	-9999	-0.55	7	7
Aurora B/Septin1	0.016	0.11	-9999	-0.59	6	6
AURKA	0.012	0.026	-9999	-0.43	1	1
INCENP	0.014	0.003	-9999	-10000	0	0
KLHL13	-0.096	0.18	-9999	-0.38	78	78
BUB1	0.009	0.045	-9999	-0.43	3	3
hSgo1/Aurora B/Survivin	0.018	0.06	-9999	-0.31	8	8
EVI5	0.008	0.052	-9999	-0.43	4	4
RhoA/GTP	0.025	0.084	-9999	-0.53	5	5
SGOL1	0.007	0.052	-9999	-0.43	4	4
CENPA	0.014	0.088	-9999	-0.53	6	6
NCAPG	0.007	0.052	-9999	-0.43	4	4
Aurora B/HC8 Proteasome	0.017	0.038	-9999	-0.3	4	4
NCAPD2	0.014	0	-9999	-10000	0	0
Aurora B/PP1-gamma	0.016	0.042	-9999	-0.3	5	5
RHOA	0.014	0	-9999	-10000	0	0
NCAPH	0.009	0.045	-9999	-0.43	3	3
NPM1	0.01	0.062	-9999	-0.5	4	4
RASA1	0.009	0.045	-9999	-0.43	3	3
KLHL9	0.003	0.069	-9999	-0.43	7	7
mitotic prometaphase	0	0.002	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.017	0.038	-9999	-0.3	4	4
PPP1CC	0.012	0.026	-9999	-0.43	1	1
Centraspindlin	0.028	0.091	-9999	-0.51	6	6
RhoA/GDP	0.01	0	-9999	-10000	0	0
NSUN2	0.01	0.062	-9999	-0.5	4	4
MYLK	0.008	0.043	-9999	-0.29	5	5
KIF23	0.011	0.038	-9999	-0.44	2	2
VIM	0.016	0.038	-9999	-0.3	4	4
RACGAP1	0.014	0.002	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
NCL	0.01	0.062	-9999	-0.5	4	4
Chromosomal passenger complex	0.02	0.086	-9999	-0.45	7	7
Chromosomal passenger complex/EVI5	0.032	0.069	-9999	-0.27	11	11
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

×

PLK2 and PLK4 events

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
PLK2	0.007	0.052	-9999	-0.43	4	4
PLK4	0.004	0.064	-9999	-0.43	6	6
regulation of centriole replication	0.008	0.062	-9999	-0.32	9	9

×

Insulin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.019	0.058	-9999	-0.29	3	3
TC10/GTP	-0.01	0.041	-9999	-0.3	1	1
Insulin Receptor/Insulin/IRS1/Shp2	0.017	0.054	-9999	-0.22	13	13
HRAS	0.014	0	-9999	-10000	0	0
APS homodimer	0.003	0.069	-9999	-0.43	7	7
GRB14	-0.07	0.16	-9999	-0.37	60	60
FOXO3	0.006	0.068	-9999	-0.54	4	4
AKT1	-0.01	0.085	-9999	-0.31	5	5
INSR	0.013	0.026	-9999	-0.43	1	1
Insulin Receptor/Insulin	0.032	0.023	-9999	-0.28	1	1
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.004	0.064	-9999	-0.43	6	6
SORBS1	0	0.076	-9999	-0.42	9	9
CRK	0.014	0	-9999	-10000	0	0
PTPN1	0.025	0.022	-9999	-0.28	1	1
CAV1	0.01	0.052	-9999	-0.21	15	15
CBL/APS/CAP/Crk-II/C3G	0.027	0.055	-9999	-0.2	15	15
Insulin Receptor/Insulin/IRS1/NCK2	0.017	0.054	-9999	-0.22	13	13
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.009	0.057	-9999	-0.2	18	18
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.023	0.05	-9999	-0.36	2	2
RPS6KB1	-0.004	0.08	-9999	-0.28	5	5
PARD6A	0.009	0.042	-9999	-0.39	3	3
CBL	0.014	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	-0.001	0.045	-9999	-0.73	1	1
PIK3R1	0.01	0.037	-9999	-0.43	2	2
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.033	0.061	-9999	-0.28	5	5
HRAS/GTP	-0.015	0.047	-9999	-0.32	1	1
Insulin Receptor	0.013	0.026	-9999	-0.43	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.024	0.05	-9999	-0.2	13	13
PRKCI	-0.017	0.067	-9999	-0.49	5	5
Insulin Receptor/Insulin/GRB14/PDK1	-0.041	0.075	-9999	-0.31	6	6
SHC1	0.014	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0.022	0.046	-9999	-0.62	1	1
PI3K	0.014	0.059	-9999	-0.2	18	18
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	0.01	0	-9999	-10000	0	0
AKT2	-0.01	0.085	-9999	-0.31	5	5
PRKCZ	-0.02	0.079	-9999	-0.5	7	7
SH2B2	0.003	0.069	-9999	-0.43	7	7
SHC/SHIP	0.008	0.066	-9999	-0.2	23	23
F2RL2	-0.073	0.16	-9999	-0.37	63	63
TRIP10	0.012	0.026	-9999	-0.43	1	1
Insulin Receptor/Insulin/Shc	0.019	0.014	-9999	-0.21	1	1
TC10/GTP/CIP4/Exocyst	0.017	0.016	-9999	-0.25	1	1
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.034	0.013	-9999	-0.18	1	1
RAPGEF1	0.014	0	-9999	-10000	0	0
RASA1	0.009	0.045	-9999	-0.43	3	3
NCK1	0.014	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	0.021	0.058	-9999	-0.22	15	15
TC10/GDP	0.01	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.023	0.039	-9999	-0.22	7	7
INPP5D	0	0.069	-9999	-0.22	23	23
SOS1	0.014	0	-9999	-10000	0	0
SGK1	-0.013	0.094	-9999	-0.8	4	4
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.014	0	-9999	-10000	0	0
IRS1	-0.006	0.091	-9999	-0.42	13	13
p62DOK/RasGAP	0.022	0.046	-9999	-0.63	1	1
INS	0.002	0.003	-9999	-10000	0	0
mol:PI-3-4-P2	0	0.068	-9999	-0.21	23	23
GRB2	0.014	0	-9999	-10000	0	0
EIF4EBP1	-0.004	0.081	-9999	-0.28	6	6
PTPRA	0.015	0.003	-9999	-10000	0	0
PIK3CA	0.007	0.052	-9999	-0.43	4	4
TC10/GTP/CIP4	0.017	0.016	-9999	-0.25	1	1
PDPK1	0.014	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.018	0.048	-9999	-0.2	13	13
Insulin Receptor/Insulin/IRS1	0.008	0.053	-9999	-0.22	14	14
Insulin Receptor/Insulin/IRS3	0.012	0.019	-9999	-0.3	1	1
Par3/Par6	-0.015	0.086	-9999	-0.2	37	37

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.006	0.073	-9999	-0.33	8	8
PDGFB-D/PDGFRB/SLAP	-0.002	0.079	-9999	-0.28	21	21
PDGFB-D/PDGFRB/APS/CBL	0.018	0.05	-9999	-0.24	10	10
AKT1	0.031	0.055	-9999	-0.48	1	1
mol:PI-4-5-P2	0	0.001	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.006	0.076	-9999	-0.34	8	8
PIK3CA	0.007	0.052	-9999	-0.43	4	4
FGR	-0.018	0.098	-9999	-0.43	14	14
mol:Ca2+	0.007	0.068	-9999	-0.46	4	4
MYC	0.018	0.067	-9999	-0.38	2	2
SHC1	0.014	0	-9999	-10000	0	0
HRAS/GDP	0.027	0.039	-9999	-0.22	6	6
LRP1/PDGFRB/PDGFB	0.024	0.03	-9999	-0.22	4	4
GRB10	0.004	0.064	-9999	-0.43	6	6
PTPN11	0.014	0	-9999	-10000	0	0
GO:0007205	0.007	0.069	-9999	-0.47	4	4
PTEN	0.003	0.069	-9999	-0.43	7	7
GRB2	0.014	0	-9999	-10000	0	0
GRB7	-0.027	0.1	-9999	-0.31	33	33
PDGFB-D/PDGFRB/SHP2	0.017	0.032	-9999	-0.3	3	3
PDGFB-D/PDGFRB/GRB10	0.01	0.056	-9999	-0.3	9	9
cell cycle arrest	-0.002	0.079	-9999	-0.28	21	21
HRAS	0.014	0	-9999	-10000	0	0
HIF1A	0.034	0.053	-9999	-0.36	2	2
GAB1	-0.002	0.082	-9999	-0.4	6	6
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.003	0.076	-9999	-0.36	6	6
PDGFB-D/PDGFRB	0.026	0.035	-9999	-0.25	4	4
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.016	0.035	-9999	-0.27	4	4
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.017	0.067	-9999	-0.3	11	11
positive regulation of MAPKKK cascade	0.017	0.032	-9999	-0.3	3	3
PIK3R1	0.01	0.037	-9999	-0.43	2	2
mol:IP3	0.007	0.069	-9999	-0.47	4	4
E5	0	0.001	-9999	-10000	0	0
CSK	0.013	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.011	0.079	-9999	-0.22	36	36
SHB	-0.02	0.11	-9999	-0.4	23	23
BLK	-0.068	0.17	-9999	-0.49	36	36
PTPN2	0.012	0.027	-9999	-0.44	1	1
PDGFB-D/PDGFRB/SNX15	0.017	0.032	-9999	-0.3	3	3
BCAR1	0.009	0.045	-9999	-0.43	3	3
VAV2	0.001	0.087	-9999	-0.36	9	9
CBL	0.014	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.015	0.042	-9999	-0.3	5	5
LCK	-0.073	0.18	-9999	-0.49	42	42
PDGFRB	0.009	0.046	-9999	-0.43	3	3
ACP1	0.012	0.019	-9999	-0.31	1	1
HCK	-0.017	0.11	-9999	-0.45	15	15
ABL1	-0.005	0.083	-9999	-0.3	13	13
PDGFB-D/PDGFRB/CBL	-0.003	0.087	-9999	-0.4	7	7
PTPN1	0.013	0.019	-9999	-0.3	1	1
SNX15	0.014	0	-9999	-10000	0	0
STAT3	0.014	0	-9999	-10000	0	0
STAT1	0.012	0.026	-9999	-0.43	1	1
cell proliferation	0.018	0.063	-9999	-0.36	2	2
SLA	-0.013	0.1	-9999	-0.4	18	18
actin cytoskeleton reorganization	0.021	0.065	-9999	-0.37	1	1
SRC	-0.001	0.045	-9999	-0.31	5	5
PI3K	-0.012	0.049	-9999	-0.54	1	1
PDGFB-D/PDGFRB/GRB7/SHC	0.001	0.067	-9999	-0.17	36	36
SH2B2	0.003	0.069	-9999	-0.43	7	7
PLCgamma1/SPHK1	0.006	0.078	-9999	-0.35	8	8
LYN	0	0.047	-9999	-0.32	5	5
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	0.012	0.026	-9999	-0.43	1	1
NCK1-2/p130 Cas	0.037	0.036	-9999	-0.19	3	3
SPHK1	-0.007	0.088	-9999	-0.36	16	16
EDG1	0	0.002	-9999	-10000	0	0
mol:DAG	0.007	0.069	-9999	-0.47	4	4
PLCG1	0.006	0.071	-9999	-0.48	4	4
NHERF/PDGFRB	0.022	0.039	-9999	-0.22	7	7
YES1	-0.007	0.082	-9999	-0.44	8	8
cell migration	0.021	0.039	-9999	-0.22	7	7
SHC/Grb2/SOS1	0.04	0.028	-9999	-0.19	2	2
SLC9A3R2	0.011	0.032	-9999	-0.37	2	2
SLC9A3R1	0.011	0.032	-9999	-0.37	2	2
NHERF1-2/PDGFRB/PTEN	0.023	0.052	-9999	-0.21	12	12
FYN	0.002	0.036	-9999	-0.27	4	4
DOK1	0.022	0.035	-9999	-0.22	5	5
HRAS/GTP	0.01	0	-9999	-10000	0	0
PDGFB	0.012	0.019	-9999	-0.31	1	1
RAC1	0.011	0.082	-9999	-0.4	5	5
PRKCD	0.024	0.031	-9999	-0.22	4	4
FER	0.019	0.048	-9999	-0.24	8	8
MAPKKK cascade	-0.002	0.023	-9999	-0.18	1	1
RASA1	0.021	0.044	-9999	-0.26	6	6
NCK1	0.014	0	-9999	-10000	0	0
NCK2	0.014	0	-9999	-10000	0	0
p62DOK/Csk	0.029	0.033	-9999	-0.19	5	5
PDGFB-D/PDGFRB/SHB	-0.007	0.087	-9999	-0.28	26	26
chemotaxis	-0.005	0.081	-9999	-0.29	13	13
STAT1-3-5/STAT1-3-5	0.006	0.032	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0.007	0.032	-9999	-0.31	3	3
PTPRJ	0.01	0.037	-9999	-0.43	2	2

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.009	0.029	-10000	0	-0.18	6	6
TRAF2/ASK1	0.013	0.035	-10000	0	-0.22	6	6
ATM	0.006	0.058	-10000	0	-0.43	5	5
MAP2K3	0.006	0.1	-10000	0	-0.48	10	10
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.006	0.098	-10000	0	-0.31	16	16
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	-0.031	0.13	-10000	0	-0.39	31	31
TXN	0.008	0	-10000	0	-10000	0	0
CALM1	0.014	0	-10000	0	-10000	0	0
GADD45A	0.011	0.027	-10000	0	-0.31	2	2
GADD45B	0.014	0	-10000	0	-10000	0	0
MAP3K1	0.003	0.069	-10000	0	-0.43	7	7
MAP3K6	0.014	0	-10000	0	-10000	0	0
MAP3K7	0.009	0.045	-10000	0	-0.43	3	3
MAP3K4	0.014	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.014	0.042	-10000	0	-0.26	6	6
TAK1/TAB family	-0.001	0.028	0.16	4	-0.2	3	7
RAC1/OSM/MEKK3	0.026	0	-10000	0	-10000	0	0
TRAF2	0.014	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.014	0.071	-10000	0	-0.35	10	10
TRAF6	0.008	0	-10000	0	-10000	0	0
RAC1	0.014	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.041	0.13	-10000	0	-0.34	43	43
CCM2	0.014	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.013	0.076	-10000	0	-0.19	43	43
MAPK11	0.007	0.052	-10000	0	-0.43	4	4
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.007	0.074	-10000	0	-0.22	16	16
OSM/MEKK3	0.02	0	-10000	0	-10000	0	0
TAOK1	0	0.078	-10000	0	-0.35	12	12
TAOK2	0.01	0.039	-10000	0	-0.28	5	5
TAOK3	0.01	0.039	-10000	0	-0.28	5	5
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	0.005	0.059	-10000	0	-0.39	6	6
MAP3K10	0.007	0.052	-10000	0	-0.43	4	4
MAP3K3	0.014	0	-10000	0	-10000	0	0
TRX/ASK1	0.011	0.034	-10000	0	-0.22	6	6
GADD45/MTK1/MTK1	0.008	0.067	-10000	0	-0.2	22	22

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0.008	0.07	0.21	30	-10000	0	30
KIRREL	0.007	0.046	-10000	0	-0.43	3	3
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.008	0.07	-10000	0	-0.21	30	30
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	0.003	0.056	-10000	0	-0.23	6	6
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.015	0.033	-10000	0	-0.21	3	3
FYN	0.002	0.043	-10000	0	-0.21	3	3
mol:Ca2+	0.005	0.049	-10000	0	-0.21	3	3
mol:DAG	0.006	0.049	-10000	0	-0.21	3	3
NPHS2	0	0.009	-10000	0	-10000	0	0
mol:IP3	0.006	0.049	-10000	0	-0.21	3	3
regulation of endocytosis	0.011	0.042	-10000	0	-0.19	3	3
Nephrin/NEPH1/podocin/Cholesterol	-0.003	0.049	-10000	0	-0.22	3	3
establishment of cell polarity	-0.008	0.07	-10000	0	-0.21	30	30
Nephrin/NEPH1/podocin/NCK1-2	0.014	0.046	-10000	0	-0.19	3	3
Nephrin/NEPH1/beta Arrestin2	0.012	0.042	-10000	0	-0.19	3	3
NPHS1	-0.022	0.091	-10000	0	-0.3	27	27
Nephrin/NEPH1/podocin	0.002	0.044	-10000	0	-0.21	3	3
TJP1	0.004	0.064	-10000	0	-0.43	6	6
NCK1	0.014	0	-10000	0	-10000	0	0
NCK2	0.014	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.006	0.05	-10000	0	-0.21	3	3
CD2AP	0.009	0.045	-10000	0	-0.43	3	3
Nephrin/NEPH1/podocin/GRB2	0.006	0.05	-10000	0	-0.21	3	3
GRB2	0.014	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.005	0.059	-10000	0	-0.22	9	9
cytoskeleton organization	0.017	0.038	-10000	0	-0.22	3	3
Nephrin/NEPH1	-0.003	0.047	-10000	0	-0.21	3	3
Nephrin/NEPH1/ZO-1	-0.002	0.069	-10000	0	-0.27	9	9

×

BARD1 signaling events

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
BARD1/CSTF1	0.011	0.052	-10000	0	-0.3	8	8
ATM	0.006	0.058	-10000	0	-0.43	5	5
UBE2D3	0.014	0	-10000	0	-10000	0	0
PRKDC	0.014	0	-10000	0	-10000	0	0
ATR	0.012	0.026	-10000	0	-0.43	1	1
UBE2L3	0.014	0	-10000	0	-10000	0	0
FANCD2	0.015	0.046	-10000	0	-0.28	7	7
protein ubiquitination	0.017	0.072	-10000	0	-0.23	21	21
XRCC5	0.014	0	-10000	0	-10000	0	0
XRCC6	0.014	0	-10000	0	-10000	0	0
M/R/N Complex	0.017	0.062	-10000	0	-0.33	8	8
MRE11A	0.009	0.045	-10000	0	-0.43	3	3
DNA-PK	0.028	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.039	0.028	-10000	0	-10000	0	0
FANCF	0.014	0	-10000	0	-10000	0	0
BRCA1	0.01	0.037	-10000	0	-0.43	2	2
CCNE1	0.012	0.019	-10000	0	-0.31	1	1
CDK2/Cyclin E1	0.009	0.057	-10000	0	-0.29	10	10
FANCG	0.014	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.009	0.066	-10000	0	-0.36	8	8
FANCE	0.014	0	-10000	0	-10000	0	0
FANCC	0.014	0	-10000	0	-10000	0	0
NBN	0.01	0.037	-10000	0	-0.43	2	2
FANCA	0.014	0	-10000	0	-10000	0	0
DNA repair	0.045	0.057	-10000	0	-0.35	3	3
BRCA1/BARD1/ubiquitin	0.009	0.066	-10000	0	-0.36	8	8
BARD1/DNA-PK	0.028	0.041	-10000	0	-0.21	8	8
FANCL	0.012	0.026	-10000	0	-0.43	1	1
mRNA polyadenylation	-0.011	0.052	0.3	8	-10000	0	8
BRCA1/BARD1/CTIP/M/R/N Complex	0.009	0.12	-10000	0	-0.46	14	14
BRCA1/BACH1/BARD1/TopBP1	0.018	0.057	-10000	0	-0.3	8	8
BRCA1/BARD1/P53	0.022	0.061	-10000	0	-0.25	13	13
BARD1/CSTF1/BRCA1	0.018	0.057	-10000	0	-0.3	8	8
BRCA1/BACH1	0.01	0.037	-10000	0	-0.43	2	2
BARD1	0.001	0.074	-10000	0	-0.43	8	8
PCNA	0.014	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	0.018	0.057	-10000	0	-0.3	8	8
BRCA1/BARD1/UbcH7	0.018	0.057	-10000	0	-0.3	8	8
BRCA1/BARD1/RAD51/PCNA	0.025	0.056	-10000	0	-0.26	10	10
BARD1/DNA-PK/P53	0.03	0.047	-10000	0	-0.19	12	12
BRCA1/BARD1/Ubiquitin	0.009	0.066	-10000	0	-0.36	8	8
BRCA1/BARD1/CTIP	0.015	0.074	-10000	0	-0.29	14	14
FA complex	0.034	0.017	-10000	0	-10000	0	0
BARD1/EWS	0.011	0.052	-10000	0	-0.3	8	8
RBBP8	0.009	0.059	-10000	0	-0.33	8	8
TP53	0.007	0.052	-10000	0	-0.43	4	4
TOPBP1	0.014	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.021	0.061	0.24	13	-10000	0	13
BRCA1/BARD1	0.02	0.074	-10000	0	-0.23	21	21
CSTF1	0.014	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.001	0.052	-10000	0	-0.3	8	8
CDK2	-0.001	0.078	-10000	0	-0.43	9	9
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.01	0.037	-10000	0	-0.43	2	2
RAD50	0.004	0.064	-10000	0	-0.43	6	6
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.009	0.066	-10000	0	-0.36	8	8
EWSR1	0.014	0	-10000	0	-10000	0	0

×

EPO signaling 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
BCL2L1	0.04	0.08	-10000	0	-0.42	2	2
CRKL	0.016	0.063	-10000	0	-0.33	3	3
mol:DAG	0.025	0.061	-10000	0	-0.34	3	3
HRAS	0.032	0.06	-10000	0	-0.27	5	5
MAPK8	0.017	0.046	-10000	0	-0.24	5	5
RAP1A	0.016	0.063	-10000	0	-0.33	3	3
GAB1	0.015	0.068	-10000	0	-0.33	5	5
MAPK14	0.021	0.034	-10000	0	-0.26	1	1
EPO	-0.003	0.061	-10000	0	-0.3	11	11
PLCG1	0.025	0.062	-10000	0	-0.35	3	3
EPOR/TRPC2/IP3 Receptors	0.014	0.008	-10000	0	-10000	0	0
RAPGEF1	0.014	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.013	0.055	-10000	0	-0.24	8	8
GAB1/SHC/GRB2/SOS1	0.028	0.062	-10000	0	-0.28	5	5
EPO/EPOR (dimer)	0.01	0.044	-10000	0	-0.2	11	11
IRS2	0.015	0.064	-10000	0	-0.27	5	5
STAT1	0.03	0.074	-10000	0	-0.42	3	3
STAT5B	0.028	0.066	-10000	0	-0.35	3	3
cell proliferation	0.021	0.043	-10000	0	-0.22	5	5
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.024	0.074	-10000	0	-0.32	13	13
TEC	0.007	0.079	-10000	0	-0.33	6	6
SOCS3	0.003	0.066	-10000	0	-0.41	7	7
STAT1 (dimer)	0.03	0.073	-10000	0	-0.41	3	3
JAK2	0.003	0.067	-10000	0	-0.41	7	7
PIK3R1	0.01	0.037	-10000	0	-0.43	2	2
EPO/EPOR (dimer)/JAK2	0.026	0.072	-10000	0	-0.23	10	10
EPO/EPOR	0.01	0.044	-10000	0	-0.2	11	11
LYN	0.013	0.027	-10000	0	-0.43	1	1
TEC/VAV2	0.01	0.085	-10000	0	-0.35	6	6
elevation of cytosolic calcium ion concentration	0.014	0.008	-10000	0	-10000	0	0
SHC1	0.014	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	0.024	0.041	-10000	0	-0.24	2	2
mol:IP3	0.025	0.061	-10000	0	-0.34	3	3
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.017	0.093	-10000	0	-0.32	15	15
SH2B3	0.007	0.054	-10000	0	-0.44	4	4
NFKB1	0.021	0.034	-10000	0	-0.26	1	1
EPO/EPOR (dimer)/JAK2/SOCS3	-0.001	0.056	0.24	4	-0.23	9	13
PTPN6	0.011	0.066	-10000	0	-0.23	10	10
TEC/VAV2/GRB2	0.016	0.083	-10000	0	-0.33	6	6
EPOR	0.014	0.008	-10000	0	-10000	0	0
INPP5D	-0.009	0.095	-10000	0	-0.39	16	16
mol:GDP	0.028	0.062	-10000	0	-0.29	5	5
SOS1	0.014	0	-10000	0	-10000	0	0
PLCG2	-0.001	0.078	-10000	0	-0.4	10	10
CRKL/CBL/C3G	0.03	0.062	-10000	0	-0.3	3	3
VAV2	0.011	0.071	-10000	0	-0.29	6	6
CBL	0.016	0.063	-10000	0	-0.33	3	3
SHC/Grb2/SOS1	-0.015	0.045	-10000	0	-0.3	3	3
STAT5A	0.027	0.071	-10000	0	-0.42	3	3
GRB2	0.014	0	-10000	0	-10000	0	0
STAT5 (dimer)	0.039	0.084	-10000	0	-0.3	10	10
LYN/PLCgamma2	0.01	0.062	-10000	0	-0.3	10	10
PTPN11	0.014	0	-10000	0	-10000	0	0
BTK	0.007	0.084	-10000	0	-0.3	13	13
BCL2	0.026	0.15	-10000	0	-0.76	9	9

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	-0.044	0.13	-9999	-0.3	57	57
AKT1	0.034	0.11	-9999	-0.44	10	10
PTK2B	-0.012	0.11	-9999	-0.33	15	15
VEGFR2 homodimer/Frs2	0.025	0.047	-9999	-0.58	1	1
CAV1	0.01	0.037	-9999	-0.43	2	2
CALM1	0.014	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.027	0.057	-9999	-0.53	1	1
endothelial cell proliferation	0.023	0.11	-9999	-0.37	10	10
mol:Ca2+	0.028	0.065	-9999	-0.43	2	2
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.035	0.053	-9999	-0.5	1	1
RP11-342D11.1	0.02	0.064	-9999	-0.43	2	2
CDH5	0.014	0	-9999	-10000	0	0
VEGFA homodimer	0.028	0.037	-9999	-0.21	2	2
SHC1	0.014	0	-9999	-10000	0	0
SHC2	-0.054	0.16	-9999	-0.41	45	45
HRAS/GDP	-0.011	0.044	-9999	-0.36	2	2
SH2D2A	-0.006	0.089	-9999	-0.41	13	13
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.037	0.093	-9999	-0.42	7	7
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.018	0.08	-9999	-0.47	3	3
VEGFR1 homodimer	0.009	0.042	-9999	-0.39	3	3
SHC/GRB2/SOS1	0.038	0.062	-9999	-0.4	2	2
GRB10	0.023	0.091	-9999	-0.46	8	8
PTPN11	0.014	0	-9999	-10000	0	0
GRB2	0.014	0	-9999	-10000	0	0
PAK1	0.01	0.037	-9999	-0.35	3	3
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.04	0.051	-9999	-0.47	1	1
HRAS	0.014	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	-0.01	0.12	-9999	-0.46	11	11
HIF1A	0.012	0.026	-9999	-0.43	1	1
FRS2	0.011	0.027	-9999	-0.31	2	2
oxygen and reactive oxygen species metabolic process	0.034	0.052	-9999	-0.49	1	1
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.007	0.049	-9999	-0.36	5	5
Nck/Pak	0.017	0.026	-9999	-0.23	3	3
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.028	0.056	-9999	-0.53	1	1
mol:GDP	-0.012	0.047	-9999	-0.39	2	2
mol:NADP	0.037	0.077	-9999	-0.36	6	6
eNOS/Hsp90	0.041	0.075	-9999	-0.34	6	6
PIK3R1	0.01	0.037	-9999	-0.43	2	2
mol:IP3	0.028	0.065	-9999	-0.43	2	2
HIF1A/ARNT	0.019	0.019	-9999	-0.3	1	1
SHB	-0.02	0.11	-9999	-0.4	23	23
VEGFA	0.001	0.065	-9999	-0.31	11	11
VEGFC	0.007	0.046	-9999	-0.31	6	6
FAK1/Vinculin	0.007	0.11	-9999	-0.44	8	8
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.012	0.12	-9999	-0.36	13	13
PTPN6	-0.006	0.088	-9999	-0.38	14	14
EPAS1	0.019	0.027	-9999	-0.31	1	1
mol:L-citrulline	0.037	0.077	-9999	-0.36	6	6
ITGAV	0.003	0.069	-9999	-0.43	7	7
PIK3CA	0.007	0.052	-9999	-0.43	4	4
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.034	0.055	-9999	-0.5	1	1
VEGFR2 homodimer/VEGFA homodimer	0.028	0.072	-9999	-0.47	2	2
VEGFR2/3 heterodimer	0.023	0.06	-9999	-0.51	2	2
VEGFB	0.014	0	-9999	-10000	0	0
MAPK11	0.028	0.067	-9999	-0.45	2	2
VEGFR2 homodimer	0.023	0.052	-9999	-0.34	4	4
FLT1	0.009	0.042	-9999	-0.39	3	3
NEDD4	0.009	0.046	-9999	-0.43	3	3
MAPK3	0.015	0.069	-9999	-0.33	4	4
MAPK1	0.015	0.069	-9999	-0.33	4	4
VEGFA145/NRP2	0.006	0.066	-9999	-0.26	14	14
VEGFR1/2 heterodimer	0.024	0.051	-9999	-0.35	3	3
KDR	0.023	0.052	-9999	-0.35	4	4
VEGFA165/NRP1/VEGFR2 homodimer	0.029	0.073	-9999	-0.37	4	4
SRC	0.012	0.026	-9999	-0.43	1	1
platelet activating factor biosynthetic process	0.017	0.069	-9999	-0.33	4	4
PI3K	0.026	0.11	-9999	-0.45	10	10
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.028	0.056	-9999	-0.53	1	1
FES	0.02	0.081	-9999	-0.43	4	4
GAB1	0.037	0.072	-9999	-0.46	3	3
VEGFR2 homodimer/VEGFA homodimer/Src	0.027	0.057	-9999	-0.53	1	1
CTNNB1	0.014	0	-9999	-10000	0	0
SOS1	0.014	0	-9999	-10000	0	0
ARNT	0.014	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.041	0.075	-9999	-0.34	6	6
VEGFR2 homodimer/VEGFA homodimer/Yes	0.024	0.063	-9999	-0.53	1	1
PI3K/GAB1	0.036	0.11	-9999	-0.45	9	9
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.037	0.055	-9999	-0.47	1	1
PRKACA	0.014	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.027	0.06	-9999	-0.74	1	1
HSP90AA1	0.012	0.026	-9999	-0.43	1	1
CDC42	0.028	0.066	-9999	-0.44	2	2
actin cytoskeleton reorganization	0.017	0.08	-9999	-0.47	3	3
PTK2	0	0.12	-9999	-0.41	12	12
EDG1	0.02	0.064	-9999	-0.43	2	2
mol:DAG	0.028	0.065	-9999	-0.43	2	2
CaM/Ca2+	0.033	0.061	-9999	-0.4	2	2
MAP2K3	0.03	0.065	-9999	-0.41	2	2
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.029	0.094	-9999	-0.47	8	8
PLCG1	0.028	0.066	-9999	-0.44	2	2
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.017	0.082	-9999	-0.35	5	5
IQGAP1	0.014	0	-9999	-10000	0	0
YES1	0.006	0.058	-9999	-0.43	5	5
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.028	0.056	-9999	-0.53	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.017	0.073	-9999	-0.43	2	2
cell migration	0.029	0.099	-9999	-0.48	4	4
mol:PI-3-4-5-P3	0.026	0.1	-9999	-0.42	10	10
FYN	0.014	0	-9999	-10000	0	0
VEGFB/NRP1	0.027	0.062	-9999	-0.41	2	2
mol:NO	0.037	0.077	-9999	-0.36	6	6
PXN	0.014	0	-9999	-10000	0	0
HRAS/GTP	-0.011	0.044	-9999	-0.36	2	2
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.028	0.093	-9999	-0.46	8	8
VHL	0.014	0	-9999	-10000	0	0
ITGB3	-0.068	0.17	-9999	-0.4	55	55
NOS3	0.038	0.084	-9999	-0.41	6	6
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.009	0.098	-9999	-0.43	2	2
RAC1	0.014	0	-9999	-10000	0	0
PRKCA	0.023	0.074	-9999	-0.32	4	4
PRKCB	0.002	0.092	-9999	-0.4	4	4
VCL	0.014	0	-9999	-10000	0	0
VEGFA165/NRP1	0.023	0.066	-9999	-0.44	2	2
VEGFR1/2 heterodimer/VEGFA homodimer	0.026	0.061	-9999	-0.4	2	2
VEGFA165/NRP2	0.006	0.066	-9999	-0.26	14	14
MAPKKK cascade	0.044	0.08	-9999	-0.38	8	8
NRP2	0.006	0.058	-9999	-0.43	5	5
VEGFC homodimer	0.007	0.046	-9999	-0.31	6	6
NCK1	0.014	0	-9999	-10000	0	0
ROCK1	0.003	0.069	-9999	-0.43	7	7
FAK1/Paxillin	0.007	0.11	-9999	-0.44	8	8
MAP3K13	0.027	0.068	-9999	-0.44	2	2
PDPK1	0.029	0.095	-9999	-0.38	10	10

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.01	0.14	-10000	0	-0.99	5	5
regulation of axonogenesis	-0.019	0.03	0.3	1	-10000	0	1
myoblast fusion	-0.009	0.057	0.36	5	-10000	0	5
mol:GTP	0.004	0.033	-10000	0	-0.21	5	5
regulation of calcium-dependent cell-cell adhesion	-0.011	0.075	0.24	20	-10000	0	20
ARF1/GTP	0.013	0.025	-10000	0	-0.15	5	5
mol:GM1	0.004	0.025	-10000	0	-0.16	5	5
mol:Choline	0.017	0.033	-10000	0	-0.3	2	2
lamellipodium assembly	0.013	0.06	-10000	0	-0.39	5	5
MAPK3	0.015	0.049	-10000	0	-0.32	5	5
ARF6/GTP/NME1/Tiam1	0.012	0.075	-10000	0	-0.25	20	20
ARF1	0.014	0	-10000	0	-10000	0	0
ARF6/GDP	0.009	0.057	-10000	0	-0.36	5	5
ARF1/GDP	0.016	0.053	-10000	0	-0.33	5	5
ARF6	0.01	0.019	-10000	0	-10000	0	0
RAB11A	0.014	0	-10000	0	-10000	0	0
TIAM1	-0.014	0.11	-10000	0	-0.42	18	18
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.015	0.049	-10000	0	-0.32	5	5
actin filament bundle formation	-0.013	0.051	0.33	5	-10000	0	5
KALRN	-0.01	0.051	-10000	0	-0.24	9	9
RAB11FIP3/RAB11A	0.02	0	-10000	0	-10000	0	0
RhoA/GDP	0.013	0.052	-10000	0	-0.33	5	5
NME1	0.014	0.004	-10000	0	-10000	0	0
Rac1/GDP	0.013	0.052	-10000	0	-0.33	5	5
substrate adhesion-dependent cell spreading	0.004	0.033	-10000	0	-0.21	5	5
cortical actin cytoskeleton organization	0.013	0.06	-10000	0	-0.39	5	5
RAC1	0.014	0	-10000	0	-10000	0	0
liver development	0.004	0.033	-10000	0	-0.21	5	5
ARF6/GTP	0.004	0.033	-10000	0	-0.21	5	5
RhoA/GTP	0.013	0.025	-10000	0	-0.16	3	3
mol:GDP	0.011	0.057	-10000	0	-0.37	5	5
ARF6/GTP/RAB11FIP3/RAB11A	0.023	0.022	-10000	0	-10000	0	0
RHOA	0.014	0	-10000	0	-10000	0	0
PLD1	0.012	0.038	-10000	0	-0.22	6	6
RAB11FIP3	0.014	0	-10000	0	-10000	0	0
tube morphogenesis	0.013	0.06	-10000	0	-0.39	5	5
ruffle organization	0.019	0.03	-10000	0	-0.3	1	1
regulation of epithelial cell migration	0.004	0.033	-10000	0	-0.21	5	5
PLD2	0.014	0.025	-10000	0	-0.15	5	5
PIP5K1A	0.019	0.03	-10000	0	-0.31	1	1
mol:Phosphatidic acid	0.017	0.033	-10000	0	-0.3	2	2
Rac1/GTP	0.013	0.061	-10000	0	-0.39	5	5

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.014	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	0.009	0.057	-9999	-0.22	10	10
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.004	0.015	-9999	-10000	0	0
AURKB	0.007	0.052	-9999	-0.43	4	4
AURKC	-0.012	0.093	-9999	-0.34	20	20

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	0.016	0.077	-9999	-0.31	10	10
CaM/Ca2+	0.01	0	-9999	-10000	0	0
AKT1	0.014	0	-9999	-10000	0	0
AKT2	0.014	0	-9999	-10000	0	0
STXBP4	0.01	0.037	-9999	-0.43	2	2
mol:GTP	0	0	-9999	-10000	0	0
mol:glucose	0.018	0.08	-9999	-0.34	8	8
YWHAZ	0.014	0	-9999	-10000	0	0
CALM1	0.014	0	-9999	-10000	0	0
YWHAQ	0.014	0	-9999	-10000	0	0
TBC1D4	0.014	0.037	-9999	-0.23	6	6
mol:Ca2+	0	0	-9999	-10000	0	0
YWHAH	0.014	0	-9999	-10000	0	0
YWHAB	0.014	0	-9999	-10000	0	0
SNARE/Synip	0.026	0.023	-9999	-0.24	2	2
YWHAG	0.014	0	-9999	-10000	0	0
ASIP	-0.013	0.083	-9999	-0.31	21	21
PRKCI	0.007	0.052	-9999	-0.43	4	4
AS160/CaM/Ca2+	0.01	0	-9999	-10000	0	0
RHOQ	0.014	0	-9999	-10000	0	0
GYS1	0.026	0	-9999	-10000	0	0
PRKCZ	0.003	0.069	-9999	-0.43	7	7
TRIP10	0.012	0.026	-9999	-0.43	1	1
TC10/GTP/CIP4/Exocyst	0.017	0.016	-9999	-0.25	1	1
AS160/14-3-3	0.012	0.05	-9999	-10000	0	0
VAMP2	0.014	0	-9999	-10000	0	0
SLC2A4	0.017	0.087	-9999	-0.38	8	8
STX4	0.014	0	-9999	-10000	0	0
GSK3B	0.023	0	-9999	-10000	0	0
SFN	-0.08	0.15	-9999	-0.33	77	77
LNPEP	0.004	0.064	-9999	-0.43	6	6
YWHAE	0.014	0	-9999	-10000	0	0

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.014	0	-10000	0	-10000	0	0
mol:PIP3	-0.009	0.071	0.24	7	-0.25	17	24
FRAP1	0.01	0.023	-10000	0	-10000	0	0
AKT1	0.011	0.065	0.21	7	-0.21	17	24
INSR	0.012	0.026	-10000	0	-0.43	1	1
Insulin Receptor/Insulin	0.008	0.016	-10000	0	-0.25	1	1
mol:GTP	0.017	0.049	-10000	0	-0.31	1	1
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.004	0.018	-10000	0	-0.18	1	1
TSC2	0.013	0	-10000	0	-10000	0	0
RHEB/GDP	-0.01	0.036	-10000	0	-0.28	1	1
TSC1	0.012	0.026	-10000	0	-0.43	1	1
Insulin Receptor/IRS1	0.001	0.066	-10000	0	-0.3	13	13
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.005	0.021	-10000	0	-0.21	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.014	0	-10000	0	-10000	0	0
RPS6KB1	0.018	0.041	0.16	7	-0.23	1	8
MAP3K5	0.003	0.041	-10000	0	-0.33	4	4
PIK3R1	0.01	0.037	-10000	0	-0.43	2	2
apoptosis	0.003	0.041	-10000	0	-0.33	4	4
mol:LY294002	0	0	0.001	1	-0.001	12	13
EIF4B	0.022	0.038	0.16	7	-0.2	1	8
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.023	0.03	-10000	0	-0.19	1	1
eIF4E/eIF4G1/eIF4A1	-0.002	0.014	-10000	0	-0.17	1	1
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.007	0.069	-10000	0	-0.26	17	17
mTOR/RHEB/GTP/Raptor/GBL	0.021	0.033	0.15	7	-0.15	2	9
FKBP1A	0.013	0.019	-10000	0	-0.3	1	1
RHEB/GTP	0.018	0.044	-10000	0	-0.28	1	1
mol:Amino Acids	0	0	0.001	1	-0.001	12	13
FKBP12/Rapamycin	0.01	0.013	-10000	0	-0.21	1	1
PDPK1	0.008	0.067	0.21	7	-0.22	17	24
EIF4E	0.01	0.037	-10000	0	-0.43	2	2
ASK1/PP5C	0.012	0.074	-10000	0	-0.59	4	4
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.012	0.036	-10000	0	-0.42	2	2
TSC1/TSC2	0.019	0.053	-10000	0	-0.33	1	1
tumor necrosis factor receptor activity	0	0	0.001	12	-0.001	1	13
RPS6	0.014	0	-10000	0	-10000	0	0
PPP5C	0.014	0	-10000	0	-10000	0	0
EIF4G1	0.014	0	-10000	0	-10000	0	0
IRS1	-0.007	0.068	-10000	0	-0.33	12	12
INS	0	0.001	-10000	0	-10000	0	0
PTEN	0.002	0.069	-10000	0	-0.43	7	7
PDK2	0.006	0.069	0.21	7	-0.22	19	26
EIF4EBP1	0.013	0.003	-10000	0	-10000	0	0
PIK3CA	0.007	0.052	-10000	0	-0.43	4	4
PPP2R5D	0.015	0.022	-10000	0	-10000	0	0
peptide biosynthetic process	0.014	0.014	-10000	0	-0.22	1	1
RHEB	0.014	0	-10000	0	-10000	0	0
EIF4A1	0.014	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0.001	0.003	7	-0.003	1	8
EEF2	0.014	0.014	-10000	0	-0.22	1	1
eIF4E/4E-BP1	0.018	0.021	-10000	0	-10000	0	0

×

FoxO family signaling

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
G6PC	0.02	0.045	-9999	-10000	0	0
PLK1	0.04	0.16	-9999	-0.92	3	3
CDKN1B	0.11	0.075	-9999	-0.36	4	4
FOXO3	0.042	0.14	-9999	-0.5	4	4
KAT2B	0.008	0.067	-9999	-0.44	6	6
FOXO1/SIRT1	0.028	0.057	-9999	-0.21	11	11
CAT	0.046	0.13	-9999	-0.57	1	1
CTNNB1	0.013	0	-9999	-10000	0	0
AKT1	0.02	0.015	-9999	-10000	0	0
FOXO1	0.021	0.05	-9999	-0.22	11	11
MAPK10	0.005	0.066	-9999	-0.19	16	16
mol:GTP	0.002	0.001	-9999	-10000	0	0
FOXO4	0.066	0.056	-9999	-0.3	3	3
response to oxidative stress	0.007	0.015	-9999	-10000	0	0
FOXO3A/SIRT1	0.089	0.096	-9999	-0.49	4	4
XPO1	0.014	0	-9999	-10000	0	0
EP300	0.015	0.001	-9999	-10000	0	0
BCL2L11	0.016	0.084	-9999	-1.3	1	1
FOXO1/SKP2	0.024	0.049	-9999	-0.2	11	11
mol:GDP	0.007	0.015	-9999	-10000	0	0
RAN	0.015	0.001	-9999	-10000	0	0
GADD45A	0.09	0.077	-9999	-0.51	3	3
YWHAQ	0.014	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.039	0.049	-9999	-10000	0	0
MST1	0.013	0.047	-9999	-0.42	3	3
CSNK1D	0.014	0	-9999	-10000	0	0
CSNK1E	0.014	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.023	0.062	-9999	-10000	0	0
YWHAB	0.014	0	-9999	-10000	0	0
MAPK8	0.029	0.03	-9999	-0.22	4	4
MAPK9	0.032	0.008	-9999	-10000	0	0
YWHAG	0.014	0	-9999	-10000	0	0
YWHAE	0.014	0	-9999	-10000	0	0
YWHAZ	0.014	0	-9999	-10000	0	0
SIRT1	0.015	0.056	-9999	-0.41	4	4
SOD2	0.097	0.088	-9999	-0.47	3	3
RBL2	0.05	0.16	-9999	-1.1	3	3
RAL/GDP	0.028	0.011	-9999	-10000	0	0
CHUK	0.016	0.03	-9999	-0.43	1	1
Ran/GTP	0.014	0.002	-9999	-10000	0	0
CSNK1G2	0.009	0.045	-9999	-0.43	3	3
RAL/GTP	0.033	0.011	-9999	-10000	0	0
CSNK1G1	0.014	0	-9999	-10000	0	0
FASLG	-0.2	0.48	-9999	-1.3	46	46
SKP2	0.011	0.032	-9999	-0.37	2	2
USP7	0.015	0.001	-9999	-10000	0	0
IKBKB	0.018	0.014	-9999	-10000	0	0
CCNB1	0.046	0.13	-9999	-0.57	1	1
FOXO1-3a-4/beta catenin	0.087	0.11	-9999	-0.4	3	3
proteasomal ubiquitin-dependent protein catabolic process	0.024	0.048	-9999	-0.2	11	11
CSNK1A1	0.014	0	-9999	-10000	0	0
SGK1	0.011	0.055	-9999	-0.43	4	4
CSNK1G3	0.006	0.058	-9999	-0.43	5	5
Ran/GTP/Exportin 1	0.024	0.003	-9999	-10000	0	0
ZFAND5	0.068	0.049	-9999	-10000	0	0
SFN	-0.08	0.15	-9999	-0.33	77	77
CDK2	0	0.078	-9999	-0.43	9	9
FOXO3A/14-3-3	0.029	0.06	-9999	-0.24	3	3
CREBBP	0.014	0.001	-9999	-10000	0	0
FBXO32	0.04	0.16	-9999	-1.3	2	2
BCL6	0.06	0.1	-9999	-10000	0	0
RALB	0.015	0.001	-9999	-10000	0	0
RALA	0.015	0.001	-9999	-10000	0	0
YWHAH	0.014	0	-9999	-10000	0	0

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.055	0.046	-9999	-0.22	1	1
ERC1	0.014	0	-9999	-10000	0	0
RIP2/NOD2	-0.001	0.074	-9999	-0.26	21	21
NFKBIA	0.036	0	-9999	-10000	0	0
BIRC2	0.003	0.066	-9999	-0.41	7	7
IKBKB	0.014	0	-9999	-10000	0	0
RIPK2	0.014	0	-9999	-10000	0	0
IKBKG	0.023	0.054	-9999	-0.3	1	1
IKK complex/A20	0.025	0.079	-9999	-0.31	7	7
NEMO/A20/RIP2	0.014	0	-9999	-10000	0	0
XPO1	0.014	0	-9999	-10000	0	0
NEMO/ATM	0.026	0.066	-9999	-0.39	3	3
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.014	0	-9999	-10000	0	0
Exportin 1/RanGTP	0.018	0	-9999	-10000	0	0
IKK complex/ELKS	-0.01	0.038	-9999	-0.28	2	2
BCL10/MALT1/TRAF6	0.025	0.025	-9999	-0.24	2	2
NOD2	-0.016	0.1	-9999	-0.38	21	21
NFKB1	0.016	0	-9999	-10000	0	0
RELA	0.016	0	-9999	-10000	0	0
MALT1	0.01	0.037	-9999	-0.43	2	2
cIAP1/UbcH5C	0.013	0.047	-9999	-0.28	7	7
ATM	0.006	0.058	-9999	-0.43	5	5
TNF/TNFR1A	-0.005	0.08	-9999	-0.26	25	25
TRAF6	0.014	0	-9999	-10000	0	0
PRKCA	-0.004	0.084	-9999	-0.4	12	12
CHUK	0.012	0.026	-9999	-0.43	1	1
UBE2D3	0.014	0	-9999	-10000	0	0
TNF	-0.021	0.11	-9999	-0.38	25	25
NF kappa B1 p50/RelA	0.038	0	-9999	-10000	0	0
BCL10	0.012	0.019	-9999	-0.31	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.036	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.016	0	-9999	-10000	0	0
TNFRSF1A	0.014	0	-9999	-10000	0	0
IKK complex	0.035	0.055	-9999	-0.3	2	2
CYLD	0.014	0	-9999	-10000	0	0
IKK complex/PKC alpha	0.032	0.066	-9999	-0.28	4	4

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.024	0.05	-9999	-0.21	12	12
HDAC3	0.014	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC4	0.013	0.014	-9999	-0.2	1	1
GATA1/HDAC5	0.013	0.014	-9999	-0.2	1	1
GATA2/HDAC5	0.008	0.058	-9999	-0.25	13	13
HDAC5/BCL6/BCoR	0.028	0	-9999	-10000	0	0
HDAC9	-0.025	0.12	-9999	-0.39	27	27
Glucocorticoid receptor/Hsp90/HDAC6	0.021	0.042	-9999	-0.24	7	7
HDAC4/ANKRA2	0.018	0.027	-9999	-0.3	2	2
HDAC5/YWHAB	0.02	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.019	0	-9999	-10000	0	0
GATA2	-0.004	0.082	-9999	-0.37	13	13
HDAC4/RFXANK	0.02	0	-9999	-10000	0	0
BCOR	0.014	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.012	0.026	-9999	-0.43	1	1
HDAC5	0.014	0	-9999	-10000	0	0
GNB1/GNG2	0.008	0.061	-9999	-0.3	11	11
Histones	0.017	0.055	-9999	-0.26	1	1
ADRBK1	0.012	0.026	-9999	-0.43	1	1
HDAC4	0.014	0	-9999	-10000	0	0
XPO1	0.014	0	-9999	-10000	0	0
HDAC5/ANKRA2	0.018	0.027	-9999	-0.3	2	2
HDAC4/Ubc9	0.02	0	-9999	-10000	0	0
HDAC7	0.012	0.026	-9999	-0.43	1	1
HDAC5/14-3-3 E	0.02	0	-9999	-10000	0	0
TUBA1B	0.014	0	-9999	-10000	0	0
HDAC6	0.014	0	-9999	-10000	0	0
HDAC5/RFXANK	0.02	0	-9999	-10000	0	0
CAMK4	-0.059	0.16	-9999	-0.39	51	51
Tubulin/HDAC6	0.027	0.016	-9999	-0.24	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	0.02	-9999	-0.31	1	1
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.014	0	-9999	-10000	0	0
NR3C1	0.004	0.064	-9999	-0.43	6	6
SUMO1/HDAC4	0.029	0	-9999	-10000	0	0
SRF	0.014	0	-9999	-10000	0	0
HDAC4/YWHAB	0.02	0	-9999	-10000	0	0
Tubulin	0.019	0.019	-9999	-0.3	1	1
HDAC4/14-3-3 E	0.02	0	-9999	-10000	0	0
GNB1	0.014	0	-9999	-10000	0	0
RANGAP1	0.014	0	-9999	-10000	0	0
BCL6/BCoR	0.02	0	-9999	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0.027	0.016	-9999	-0.24	1	1
HDAC4/SRF	-0.016	0.094	-9999	-0.21	51	51
HDAC4/ER alpha	0.005	0.066	-9999	-0.28	14	14
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.017	0.055	-9999	-0.26	1	1
cell motility	0.026	0.016	-9999	-0.24	1	1
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.014	0	-9999	-10000	0	0
HDAC7/HDAC3	0.019	0.019	-9999	-0.3	1	1
BCL6	0.014	0	-9999	-10000	0	0
HDAC4/CaMK II delta B	0.014	0	-9999	-10000	0	0
Hsp90/HDAC6	0.019	0.019	-9999	-0.3	1	1
ESR1	-0.008	0.093	-9999	-0.41	14	14
HDAC6/HDAC11	0.019	0.019	-9999	-0.3	1	1
Ran/GTP/Exportin 1	0.031	0	-9999	-10000	0	0
NPC	0.008	0	-9999	-10000	0	0
MEF2C	0.006	0.058	-9999	-0.43	5	5
RAN	0.014	0	-9999	-10000	0	0
HDAC4/MEF2C	0.035	0.034	-9999	-10000	0	0
GNG2	-0.004	0.086	-9999	-0.43	11	11
NCOR2	0.012	0.026	-9999	-0.43	1	1
TUBB2A	0.012	0.026	-9999	-0.43	1	1
HDAC11	0.012	0.026	-9999	-0.43	1	1
HSP90AA1	0.012	0.026	-9999	-0.43	1	1
RANBP2	0.014	0	-9999	-10000	0	0
ANKRA2	0.01	0.037	-9999	-0.43	2	2
RFXANK	0.014	0	-9999	-10000	0	0
nuclear import	-0.027	0	-9999	-10000	0	0

×

Circadian rhythm 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
chromatin modification	0.038	0.025	-9999	-10000	0	0
CLOCK	0.007	0.061	-9999	-0.4	6	6
TIMELESS/CRY2	0.033	0.02	-9999	-10000	0	0
DEC1/BMAL1	0.007	0.042	-9999	-0.21	10	10
ATR	0.012	0.026	-9999	-0.43	1	1
NR1D1	0.029	0.022	-9999	-10000	0	0
ARNTL	0.015	0.026	-9999	-0.43	1	1
TIMELESS	0.029	0.022	-9999	-10000	0	0
NPAS2	-0.015	0.11	-9999	-0.43	20	20
CRY2	0.014	0	-9999	-10000	0	0
mol:CO	-0.012	0	-9999	-10000	0	0
CHEK1	0.014	0	-9999	-10000	0	0
mol:HEME	0.012	0	-9999	-10000	0	0
PER1	0.014	0	-9999	-10000	0	0
BMAL/CLOCK/NPAS2	0.016	0.083	-9999	-0.24	25	25
BMAL1/CLOCK	0.028	0.058	-9999	-0.36	1	1
S phase of mitotic cell cycle	0.038	0.025	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	0.038	0.025	-9999	-10000	0	0
mol:NADPH	0.012	0	-9999	-10000	0	0
PER1/TIMELESS	0.033	0.02	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	-0.006	0.055	-9999	-0.31	9	9

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.023	0.019	-9999	-0.16	2	2
BIRC5	0.009	0.045	-9999	-0.43	3	3
NFKBIA	0.024	0.012	-9999	-10000	0	0
CPEB1	-0.046	0.15	-9999	-0.43	38	38
AKT1	0.024	0.012	-9999	-10000	0	0
NDEL1	0.014	0	-9999	-10000	0	0
Aurora A/BRCA1	0.02	0.02	-9999	-0.19	2	2
NDEL1/TACC3	0.029	0.01	-9999	-10000	0	0
GADD45A	0.011	0.027	-9999	-0.31	2	2
GSK3B	0.013	0.006	-9999	-10000	0	0
PAK1/Aurora A	0.022	0.025	-9999	-0.24	1	1
MDM2	0.009	0.042	-9999	-0.34	4	4
JUB	0.012	0.026	-9999	-0.43	1	1
TPX2	0.017	0.026	-9999	-0.3	2	2
TP53	0.019	0.042	-9999	-0.28	5	5
DLG7	0.016	0.012	-9999	-0.14	1	1
AURKAIP1	0.012	0.026	-9999	-0.43	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	0.031	0.011	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.02	0.02	-9999	-0.19	2	2
AURKA	0.02	0.016	-9999	-0.17	1	1
AURKB	0.008	0.044	-9999	-0.28	6	6
CDC25B	0.024	0.014	-9999	-10000	0	0
G2/M transition checkpoint	0.021	0.018	-9999	-0.22	1	1
mRNA polyadenylation	-0.01	0.081	-9999	-0.22	37	37
Aurora A/CPEB	-0.01	0.082	-9999	-0.22	37	37
Aurora A/TACC1/TRAP/chTOG	0.037	0.017	-9999	-0.19	1	1
BRCA1	0.01	0.037	-9999	-0.43	2	2
centrosome duplication	0.022	0.025	-9999	-0.24	1	1
regulation of centrosome cycle	0.029	0.01	-9999	-10000	0	0
spindle assembly	0.036	0.017	-9999	-0.19	1	1
TDRD7	0.012	0.026	-9999	-0.43	1	1
Aurora A/RasGAP/Survivin	0.029	0.042	-9999	-0.25	5	5
CENPA	0.011	0.048	-9999	-0.38	4	4
Aurora A/PP2A	0.024	0.012	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.026	0.021	-9999	-10000	0	0
negative regulation of DNA binding	0.019	0.041	-9999	-0.28	5	5
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0.02	0	-9999	-10000	0	0
RASA1	0.009	0.045	-9999	-0.43	3	3
Ajuba/Aurora A	0.021	0.018	-9999	-0.22	1	1
mitotic prometaphase	0.001	0.01	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.02	0.016	-9999	-0.17	1	1
TACC1	0.014	0	-9999	-10000	0	0
TACC3	0.014	0	-9999	-10000	0	0
Aurora A/Antizyme1	0.03	0.018	-9999	-0.21	1	1
Aurora A/RasGAP	0.021	0.03	-9999	-0.24	3	3
OAZ1	0.014	0	-9999	-10000	0	0
RAN	0.014	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.013	0.006	-9999	-10000	0	0
GIT1	0.014	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0.025	0.022	-9999	-0.24	1	1
Importin alpha/Importin beta/TPX2	0.017	0.026	-9999	-0.3	2	2
PPP2R5D	0.014	0	-9999	-10000	0	0
Aurora A/TPX2	0.027	0.025	-9999	-0.34	1	1
PAK1	0.01	0.037	-9999	-0.35	3	3
CKAP5	0.014	0	-9999	-10000	0	0

×

Arf6 trafficking events

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
SLC2A4	-0.013	0.096	-10000	0	-0.36	20	20
CLTC	0.027	0.004	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.022	0.012	-10000	0	-10000	0	0
Dynamin 2/GTP	0.022	0	-10000	0	-10000	0	0
EXOC4	0.014	0	-10000	0	-10000	0	0
CD59	0.024	0.002	-10000	0	-10000	0	0
CPE	0.005	0.046	-10000	0	-0.18	17	17
CTNNB1	0.014	0	-10000	0	-10000	0	0
membrane fusion	0.021	0.013	-10000	0	-10000	0	0
CTNND1	0.026	0	-10000	0	-10000	0	0
DNM2	0.014	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.026	0.006	-10000	0	-10000	0	0
TSHR	-0.013	0.075	-10000	0	-0.2	37	37
INS	0.01	0.002	-10000	0	-10000	0	0
BIN1	-0.016	0.11	-10000	0	-0.42	19	19
mol:Choline	0.021	0.013	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.016	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+	0.022	0	-10000	0	-10000	0	0
JUP	0.02	0.022	-10000	0	-0.16	2	2
ASAP2/amphiphysin II	0.01	0.06	-10000	0	-0.22	18	18
ARF6/GTP	0.01	0	-10000	0	-10000	0	0
CDH1	-0.031	0.083	-10000	0	-0.16	79	79
clathrin-independent pinocytosis	0.01	0	-10000	0	-10000	0	0
MAPK8IP3	0.009	0.042	-10000	0	-0.39	3	3
positive regulation of endocytosis	0.01	0	-10000	0	-10000	0	0
EXOC2	0.014	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.031	0.039	-10000	0	-0.26	4	4
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	0.008	0.06	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.016	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.016	0.025	-10000	0	-0.22	3	3
ACAP1	0.005	0.046	-10000	0	-0.26	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.019	0.01	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.027	0.014	-10000	0	-10000	0	0
JIP4/KLC1	0.026	0	-10000	0	-10000	0	0
EXOC1	0.014	0	-10000	0	-10000	0	0
exocyst	0.031	0.04	-10000	0	-0.26	4	4
RALA/GTP	0.01	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.018	0	-10000	0	-10000	0	0
receptor recycling	0.01	0	-10000	0	-10000	0	0
CTNNA1	0.026	0	-10000	0	-10000	0	0
NME1	0.016	0	-10000	0	-10000	0	0
clathrin coat assembly	0.027	0.004	-10000	0	-10000	0	0
IL2RA	0.005	0.055	-10000	0	-0.16	26	26
VAMP3	0.016	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.01	0.036	-10000	0	-0.2	3	3
EXOC6	0.007	0.052	-10000	0	-0.43	4	4
PLD1	0.017	0.022	-10000	0	-0.24	2	2
PLD2	0.019	0	-10000	0	-10000	0	0
EXOC5	0.009	0.045	-10000	0	-0.43	3	3
PIP5K1C	0.027	0.006	-10000	0	-10000	0	0
SDC1	0.015	0.036	-10000	0	-0.16	10	10
ARF6/GDP	0.017	0	-10000	0	-10000	0	0
EXOC7	0.014	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.007	0.062	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.021	0.013	-10000	0	-10000	0	0
endocytosis	-0.009	0.06	0.22	18	-10000	0	18
SCAMP2	0.014	0	-10000	0	-10000	0	0
ADRB2	0.024	0.037	-10000	0	-10000	0	0
EXOC3	0.012	0.019	-10000	0	-0.31	1	1
ASAP2	0.014	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.023	0	-10000	0	-10000	0	0
KLC1	0.014	0	-10000	0	-10000	0	0
AVPR2	0.018	0.047	-10000	0	-10000	0	0
RALA	0.014	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.002	0.058	-10000	0	-10000	0	0

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.024	0.055	-9999	-0.58	2	2
VEGFR1 homodimer/NRP1	0.014	0.055	-9999	-0.59	2	2
mol:DAG	0.01	0.077	-9999	-0.53	2	2
VEGFR1 homodimer/NRP1/VEGFR 121	0.015	0.062	-9999	-0.47	3	3
CaM/Ca2+	0.017	0.073	-9999	-0.5	2	2
HIF1A	0.017	0.039	-9999	-0.35	3	3
GAB1	0.01	0.037	-9999	-0.43	2	2
AKT1	0.02	0.089	-9999	-0.5	4	4
PLCG1	0.01	0.077	-9999	-0.53	2	2
NOS3	0.022	0.093	-9999	-0.48	5	5
CBL	0.014	0	-9999	-10000	0	0
mol:NO	0.023	0.09	-9999	-0.46	5	5
FLT1	0.02	0.063	-9999	-0.54	3	3
PGF	-0.019	0.11	-9999	-0.4	22	22
VEGFR1 homodimer/NRP2/VEGFR121	0.02	0.073	-9999	-0.42	5	5
CALM1	0.014	0	-9999	-10000	0	0
PIK3CA	0.007	0.052	-9999	-0.43	4	4
eNOS/Hsp90	0.028	0.089	-9999	-0.48	4	4
endothelial cell proliferation	-0.015	0.11	-9999	-0.45	7	7
mol:Ca2+	0.01	0.076	-9999	-0.52	2	2
MAPK3	0.01	0.077	-9999	-0.4	3	3
MAPK1	0.01	0.077	-9999	-0.4	3	3
PIK3R1	0.01	0.037	-9999	-0.43	2	2
PLGF homodimer	-0.019	0.11	-9999	-0.4	22	22
PRKACA	0.014	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	0.01	0.037	-9999	-0.43	2	2
VEGFA homodimer	0.001	0.064	-9999	-0.32	11	11
VEGFR1 homodimer/VEGFA homodimer	0.017	0.068	-9999	-0.51	3	3
platelet activating factor biosynthetic process	0.015	0.075	-9999	-0.38	3	3
PI3K	0.017	0.089	-9999	-0.5	4	4
PRKCA	0.006	0.082	-9999	-0.42	3	3
PRKCB	-0.016	0.1	-9999	-0.42	6	6
VEGFR1 homodimer/PLGF homodimer	0.005	0.086	-9999	-0.58	2	2
VEGFA	0.001	0.064	-9999	-0.32	11	11
VEGFB	0.014	0	-9999	-10000	0	0
mol:IP3	0.01	0.077	-9999	-0.53	2	2
RASA1	0.025	0.059	-9999	-0.5	3	3
NRP2	0.006	0.058	-9999	-0.43	5	5
VEGFR1 homodimer	0.02	0.063	-9999	-0.54	3	3
VEGFB homodimer	0.014	0	-9999	-10000	0	0
NCK1	0.014	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.028	0.089	-9999	-0.48	4	4
PTPN11	0.014	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.016	0.087	-9999	-0.49	4	4
mol:L-citrulline	0.023	0.09	-9999	-0.46	5	5
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.029	0.066	-9999	-0.42	4	4
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.024	0.063	-9999	-0.46	3	3
CD2AP	0.009	0.045	-9999	-0.43	3	3
PI3K/GAB1	0.021	0.09	-9999	-0.52	4	4
PDPK1	0.016	0.082	-9999	-0.46	4	4
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.024	0.063	-9999	-0.46	3	3
mol:NADP	0.023	0.09	-9999	-0.46	5	5
HSP90AA1	0.012	0.026	-9999	-0.43	1	1
ubiquitin-dependent protein catabolic process	0.028	0.065	-9999	-0.42	4	4
VEGFR1 homodimer/NRP2	0.019	0.065	-9999	-0.58	2	2

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.006	0.028	0.23	4	-10000	0	4
BUB1B	0.015	0.038	-10000	0	-0.29	4	4
PLK1	0.014	0.013	-10000	0	-0.093	2	2
PLK1S1	0.013	0.006	-10000	0	-10000	0	0
KIF2A	0.017	0.023	-10000	0	-0.22	2	2
regulation of mitotic centrosome separation	0.014	0.013	-10000	0	-0.092	2	2
GOLGA2	0.014	0	-10000	0	-10000	0	0
Hec1/SPC24	0.021	0.052	-10000	0	-0.28	7	7
WEE1	0.018	0.041	-10000	0	-0.45	2	2
cytokinesis	0.019	0.055	-10000	0	-0.23	10	10
PP2A-alpha B56	0.03	0.064	-10000	0	-0.59	3	3
AURKA	0.012	0.016	-10000	0	-0.23	1	1
PICH/PLK1	0.027	0.03	-10000	0	-0.21	3	3
CENPE	0	0.067	-10000	0	-0.22	23	23
RhoA/GTP	0.01	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.017	0.023	-10000	0	-0.22	2	2
PPP2CA	0.014	0	-10000	0	-10000	0	0
FZR1	0.014	0	-10000	0	-10000	0	0
TPX2	0.011	0.025	-10000	0	-0.28	2	2
PAK1	0.009	0.038	-10000	0	-0.35	3	3
SPC24	0.004	0.064	-10000	0	-0.43	6	6
FBXW11	0.014	0	-10000	0	-10000	0	0
CLSPN	0.005	0.053	-10000	0	-0.3	8	8
GORASP1	0.014	0	-10000	0	-10000	0	0
metaphase	0	0.001	-10000	0	-0.016	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.008	0.006	-10000	0	-0.05	2	2
G2 phase of mitotic cell cycle	0	0.001	0.01	1	-0.011	1	2
STAG2	0.007	0.052	-10000	0	-0.43	4	4
GRASP65/GM130/RAB1/GTP	0.022	0.003	-10000	0	-10000	0	0
spindle elongation	0.014	0.013	-10000	0	-0.092	2	2
ODF2	0.013	0.001	-10000	0	-10000	0	0
BUB1	0.015	0.069	-10000	0	-0.65	3	3
TPT1	0.013	0.006	-10000	0	-10000	0	0
CDC25C	0.008	0.054	-10000	0	-0.39	5	5
CDC25B	0.014	0.001	-10000	0	-10000	0	0
SGOL1	0.006	0.028	-10000	0	-0.23	4	4
RHOA	0.014	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.002	0.019	-10000	0	-0.21	2	2
CDC14B	0.01	0.001	-10000	0	-10000	0	0
CDC20	0.009	0.045	-10000	0	-0.43	3	3
PLK1/PBIP1	0.013	0.031	-10000	0	-0.23	4	4
mitosis	0	0.002	0.04	1	-10000	0	1
FBXO5	0.017	0.009	-10000	0	-10000	0	0
CDC2	0.001	0.001	-10000	0	-10000	0	0
NDC80	0.009	0.045	-10000	0	-0.43	3	3
metaphase plate congression	0.014	0.008	-10000	0	-10000	0	0
ERCC6L	0.026	0.032	-10000	0	-0.21	4	4
NLP/gamma Tubulin	0.011	0.007	-10000	0	-0.061	1	1
microtubule cytoskeleton organization	0.013	0.006	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	0	0.001	0.009	1	-10000	0	1
PPP1R12A	0.007	0.053	-10000	0	-0.43	4	4
interphase	0	0.001	0.009	1	-10000	0	1
PLK1/PRC1-2	0.026	0.036	-10000	0	-0.36	2	2
GRASP65/GM130/RAB1/GTP/PLK1	0.032	0.01	-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	0.015	0.01	-10000	0	-10000	0	0
mitotic prometaphase	0	0.001	-10000	0	-0.011	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.029	0.016	-10000	0	-10000	0	0
microtubule-based process	0.019	0.027	-10000	0	-0.28	2	2
Golgi organization	0.014	0.013	-10000	0	-0.092	2	2
Cohesin/SA2	0.015	0.03	-10000	0	-0.19	5	5
PPP1CB/MYPT1	0.014	0.047	-10000	0	-0.36	4	4
KIF20A	0.01	0.037	-10000	0	-0.43	2	2
APC/C/CDC20	0.018	0.028	-10000	0	-0.23	3	3
PPP2R1A	0.014	0	-10000	0	-10000	0	0
chromosome segregation	0.013	0.031	-10000	0	-0.23	4	4
PRC1	0.012	0.026	-10000	0	-0.43	1	1
ECT2	0.014	0.039	-10000	0	-0.24	6	6
C13orf34	0.016	0.01	-10000	0	-10000	0	0
NUDC	0.014	0.008	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	0.015	0.038	-10000	0	-0.29	4	4
spindle assembly	0.014	0.01	-10000	0	-0.083	1	1
spindle stabilization	0.013	0.006	-10000	0	-10000	0	0
APC/C/HCDH1	0.017	0.001	-10000	0	-10000	0	0
MKLP2/PLK1	0.019	0.027	-10000	0	-0.28	2	2
CCNB1	0.014	0.001	-10000	0	-10000	0	0
PPP1CB	0.012	0.027	-10000	0	-0.44	1	1
BTRC	0.014	0	-10000	0	-10000	0	0
ROCK2	0.009	0.068	-10000	0	-0.38	8	8
TUBG1	0.013	0.006	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.002	0.018	-10000	0	-0.21	2	2
MLF1IP	0.005	0.038	-10000	0	-0.31	4	4
INCENP	0.013	0.001	-10000	0	-10000	0	0

×

HIF-2-alpha transcription factor network

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
MMP14	0.002	0.021	-10000	0	-10000	0	0
oxygen homeostasis	0.007	0.011	-10000	0	-10000	0	0
TCEB2	0.012	0.026	-10000	0	-0.43	1	1
TCEB1	0.014	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	0.069	0.068	-10000	0	-0.29	1	1
EPO	0.1	0.15	-10000	0	-0.52	2	2
FIH (dimer)	0.019	0.028	-10000	0	-0.42	1	1
APEX1	0.021	0.012	-10000	0	-10000	0	0
SERPINE1	0.099	0.18	-10000	0	-0.57	8	8
FLT1	-0.003	0.084	-10000	0	-0.96	2	2
ADORA2A	0.1	0.15	-10000	0	-0.51	3	3
germ cell development	0.11	0.15	-10000	0	-0.47	4	4
SLC11A2	0.11	0.15	-10000	0	-0.49	2	2
BHLHE40	0.11	0.15	-10000	0	-0.5	3	3
HIF1AN	0.019	0.028	-10000	0	-0.42	1	1
HIF2A/ARNT/SIRT1	0.084	0.1	-10000	0	-0.31	3	3
ETS1	0.024	0.023	-10000	0	-0.3	1	1
CITED2	0.002	0.018	-10000	0	-10000	0	0
KDR	-0.001	0.062	-10000	0	-0.96	1	1
PGK1	0.11	0.15	-10000	0	-0.49	2	2
SIRT1	0.007	0.052	-10000	0	-0.43	4	4
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	0.14	0.17	-10000	0	-0.56	2	2
EPAS1	0.063	0.076	-10000	0	-0.29	3	3
SP1	0.02	0.003	-10000	0	-10000	0	0
ABCG2	0.097	0.18	-10000	0	-0.61	4	4
EFNA1	0.11	0.15	-10000	0	-0.49	2	2
FXN	0.1	0.14	-10000	0	-0.49	2	2
POU5F1	0.11	0.15	-10000	0	-0.48	4	4
neuron apoptosis	-0.14	0.16	0.55	2	-10000	0	2
EP300	0.014	0	-10000	0	-10000	0	0
EGLN3	0.006	0.078	-10000	0	-0.38	11	11
EGLN2	0.021	0.01	-10000	0	-10000	0	0
EGLN1	0.021	0.01	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.027	0.016	-10000	0	-0.24	1	1
VHL	0.014	0	-10000	0	-10000	0	0
ARNT	0.021	0.012	-10000	0	-10000	0	0
SLC2A1	0.1	0.14	-10000	0	-0.49	2	2
TWIST1	0.083	0.19	-10000	0	-0.5	11	11
ELK1	0.02	0.001	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.093	0.099	-10000	0	-0.38	1	1
VEGFA	0.11	0.16	-10000	0	-0.52	3	3
CREBBP	0.014	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	0.018	0.067	-9999	-0.25	15	15
Ran/GTP/Exportin 1/HDAC1	-0.001	0.01	-9999	-0.17	1	1
NF kappa B1 p50/RelA/I kappa B alpha	0.024	0.066	-9999	-0.24	15	15
SUMO1	0.014	0	-9999	-10000	0	0
ZFPM1	0.006	0.058	-9999	-0.43	5	5
NPC/RanGAP1/SUMO1/Ubc9	0.019	0	-9999	-10000	0	0
FKBP3	0.014	0	-9999	-10000	0	0
Histones	0.032	0.039	-9999	-10000	0	0
YY1/LSF	0.015	0.055	-9999	-0.21	15	15
SMG5	0.014	0	-9999	-10000	0	0
RAN	0.014	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	0.014	0.055	-9999	-0.2	15	15
I kappa B alpha/HDAC1	0.017	0.042	-9999	-0.21	1	1
SAP18	0.014	0	-9999	-10000	0	0
RELA	0.018	0.052	-9999	-0.19	15	15
HDAC1/Smad7	0.026	0.023	-9999	-0.24	2	2
RANGAP1	0.014	0	-9999	-10000	0	0
HDAC3/TR2	0.018	0.04	-9999	-10000	0	0
NuRD/MBD3 Complex	0.038	0.023	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.023	0.048	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.004	0.082	-9999	-0.37	13	13
GATA1	0.004	0.02	-9999	-0.31	1	1
Mad/Max	0.02	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.041	0.043	-9999	-0.31	3	3
RBBP7	0.014	0	-9999	-10000	0	0
NPC	0.008	0	-9999	-10000	0	0
RBBP4	0.014	0	-9999	-10000	0	0
MAX	0.014	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.014	0	-9999	-10000	0	0
NFKBIA	0.012	0.044	-9999	-10000	0	0
KAT2B	0.004	0.064	-9999	-0.43	6	6
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.036	0.013	-9999	-10000	0	0
SIN3 complex	0.034	0.01	-9999	-10000	0	0
SMURF1	0.014	0	-9999	-10000	0	0
CHD3	0.014	0	-9999	-10000	0	0
SAP30	0.012	0.019	-9999	-0.31	1	1
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.014	0	-9999	-10000	0	0
YY1/HDAC3	0.023	0.047	-9999	-0.3	1	1
YY1/HDAC2	0.024	0.032	-9999	-0.2	6	6
YY1/HDAC1	0.023	0.036	-9999	-0.2	7	7
NuRD/MBD2 Complex (MeCP1)	0.04	0.01	-9999	-10000	0	0
PPARG	0.007	0.082	-9999	-0.27	20	20
HDAC8/hEST1B	0.028	0	-9999	-10000	0	0
UBE2I	0.014	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.014	0	-9999	-10000	0	0
TNFRSF1A	0.014	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.017	0.042	-9999	-0.21	1	1
MBD3L2	0	0.019	-9999	-0.31	1	1
ubiquitin-dependent protein catabolic process	0.025	0.023	-9999	-0.24	2	2
CREBBP	0.014	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.041	0.024	-9999	-10000	0	0
HDAC1	0.012	0.026	-9999	-0.43	1	1
HDAC3	0.012	0.044	-9999	-10000	0	0
HDAC2	0.014	0	-9999	-10000	0	0
YY1	0.02	0.038	-9999	-0.24	6	6
HDAC8	0.014	0	-9999	-10000	0	0
SMAD7	0.012	0.026	-9999	-0.43	1	1
NCOR2	0.012	0.026	-9999	-0.43	1	1
MXD1	0.014	0	-9999	-10000	0	0
STAT3	0.023	0	-9999	-10000	0	0
NFKB1	0.014	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.014	0	-9999	-10000	0	0
YY1/LSF/HDAC1	0.022	0.053	-9999	-0.19	16	16
YY1/SAP30/HDAC1	0.029	0.034	-9999	-0.2	1	1
EP300	0.014	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.023	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.012	0.044	-9999	-10000	0	0
histone deacetylation	0.04	0.01	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.025	0.037	-9999	-10000	0	0
nuclear export	-0.027	0	-9999	-10000	0	0
PRKACA	0.014	0	-9999	-10000	0	0
GATAD2B	0.014	0	-9999	-10000	0	0
GATAD2A	0.014	0	-9999	-10000	0	0
GATA2/HDAC3	0.009	0.057	-9999	-0.21	7	7
GATA1/HDAC1	0.012	0.023	-9999	-0.25	2	2
GATA1/HDAC3	0.012	0.041	-9999	-0.21	1	1
CHD4	0.014	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.005	0.08	-9999	-0.26	25	25
SIN3/HDAC complex/Mad/Max	0.04	0.011	-9999	-10000	0	0
NuRD Complex	0.045	0.024	-9999	-10000	0	0
positive regulation of chromatin silencing	0.03	0.038	-9999	-10000	0	0
SIN3B	0.014	0	-9999	-10000	0	0
MTA2	0.014	0	-9999	-10000	0	0
SIN3A	0.014	0	-9999	-10000	0	0
XPO1	0.014	0	-9999	-10000	0	0
SUMO1/HDAC1	0.028	0.013	-9999	-0.19	1	1
HDAC complex	0.034	0.015	-9999	-0.21	1	1
GATA1/Fog1	0.008	0.044	-9999	-0.29	6	6
FKBP25/HDAC1/HDAC2	0.027	0.016	-9999	-0.24	1	1
TNF	-0.021	0.11	-9999	-0.38	25	25
negative regulation of cell growth	0.04	0.011	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.04	0.01	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.031	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.017	0.068	-9999	-0.26	15	15
SIN3/HDAC complex/NCoR1	0.038	0.011	-9999	-10000	0	0
TFCP2	-0.002	0.08	-9999	-0.42	10	10
NR2C1	0.014	0	-9999	-10000	0	0
MBD3	0.007	0.052	-9999	-0.43	4	4
MBD2	0.014	0	-9999	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.019	0	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.031	0.014	-10000	0	-0.21	1	1
CDKN1B	0.029	0.012	-10000	0	-10000	0	0
CDKN1A	0.022	0.04	-10000	0	-0.28	1	1
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.014	0	-10000	0	-10000	0	0
FOXO3	0.029	0.012	-10000	0	-10000	0	0
AKT1	0.024	0.012	-10000	0	-10000	0	0
BAD	0.012	0.026	-10000	0	-0.43	1	1
AKT3	0.014	0.018	-10000	0	-0.28	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.029	0.012	-10000	0	-10000	0	0
AKT1/ASK1	0.026	0.03	-10000	0	-0.23	1	1
BAD/YWHAZ	0.027	0.016	-10000	0	-0.24	1	1
RICTOR	0.006	0.058	-10000	0	-0.43	5	5
RAF1	0.014	0	-10000	0	-10000	0	0
JNK cascade	-0.025	0.03	0.22	1	-10000	0	1
TSC1	0.028	0.017	-10000	0	-10000	0	0
YWHAZ	0.014	0	-10000	0	-10000	0	0
AKT1/RAF1	0.031	0.012	-10000	0	-10000	0	0
EP300	0.014	0	-10000	0	-10000	0	0
mol:GDP	0.024	0.012	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.029	0.012	-10000	0	-10000	0	0
YWHAQ	0.014	0	-10000	0	-10000	0	0
TBC1D4	0.015	0.03	-10000	0	-0.24	2	2
MAP3K5	0.005	0.059	-10000	0	-0.39	6	6
MAPKAP1	0.014	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.02	0.032	-10000	0	-10000	0	0
YWHAH	0.014	0	-10000	0	-10000	0	0
AKT1S1	0.029	0.012	-10000	0	-10000	0	0
CASP9	0.029	0.012	-10000	0	-10000	0	0
YWHAB	0.014	0	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.036	0.012	-10000	0	-10000	0	0
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.026	0.023	-10000	0	-0.24	2	2
YWHAE	0.014	0	-10000	0	-10000	0	0
SRC	0.012	0.026	-10000	0	-0.43	1	1
AKT2/p21CIP1	0.027	0.039	-10000	0	-0.28	1	1
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.015	0.005	-10000	0	-10000	0	0
CHUK	0.028	0.017	-10000	0	-10000	0	0
BAD/BCL-XL	0.041	0.017	-10000	0	-10000	0	0
mTORC2	0.013	0.032	-10000	0	-0.22	5	5
AKT2	0.015	0	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.031	0.038	-10000	0	-10000	0	0
PDPK1	0.014	0	-10000	0	-10000	0	0
MDM2	0.027	0.022	-10000	0	-10000	0	0
MAPKKK cascade	-0.031	0.012	-10000	0	-10000	0	0
MDM2/Cbp/p300	0.04	0.022	-10000	0	-10000	0	0
TSC1/TSC2	0.033	0.017	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.038	0.021	-10000	0	-10000	0	0
glucose import	0.006	0.056	-10000	0	-0.22	11	11
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.025	0.01	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	0.006	0.057	-10000	0	-0.22	11	11
GSK3A	0.028	0.017	-10000	0	-10000	0	0
FOXO1	0.027	0.023	-10000	0	-0.24	1	1
GSK3B	0.029	0.012	-10000	0	-10000	0	0
SFN	-0.08	0.15	-10000	0	-0.33	77	77
G1/S transition of mitotic cell cycle	0.033	0.017	-10000	0	-10000	0	0
p27Kip1/14-3-3 family	0.018	0.045	-10000	0	-10000	0	0
PRKACA	0.014	0	-10000	0	-10000	0	0
KPNA1	0.014	0	-10000	0	-10000	0	0
HSP90AA1	0.012	0.026	-10000	0	-0.43	1	1
YWHAG	0.014	0	-10000	0	-10000	0	0
RHEB	0.014	0	-10000	0	-10000	0	0
CREBBP	0.014	0	-10000	0	-10000	0	0

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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
SMAD4	0.014	0	-9999	-10000	0	0
SMAD2	0.014	0.017	-9999	-10000	0	0
SMAD3	0.033	0.017	-9999	-10000	0	0
SMAD3/SMAD4	0.041	0.006	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	0.027	0.016	-9999	-0.24	1	1
SMAD2/SMAD2/SMAD4	0.037	0.006	-9999	-10000	0	0
PPM1A	0.014	0	-9999	-10000	0	0
CALM1	0.014	0	-9999	-10000	0	0
SMAD2/SMAD4	0.021	0.014	-9999	-10000	0	0
MAP3K1	0.003	0.069	-9999	-0.43	7	7
TRAP-1/SMAD4	0.018	0.027	-9999	-0.3	2	2
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	0.014	0	-9999	-10000	0	0
CTDSPL	0.014	0	-9999	-10000	0	0
KPNB1	0.014	0	-9999	-10000	0	0
TGFBRAP1	0.01	0.037	-9999	-0.43	2	2
UBE2I	0.014	0	-9999	-10000	0	0
NUP153	0.014	0	-9999	-10000	0	0
KPNA2	0.014	0	-9999	-10000	0	0
PIAS4	0.012	0.026	-9999	-0.43	1	1

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.012	0.026	-9999	-0.43	1	1
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
MDM2/SUMO1	0.027	0.02	-9999	-0.19	1	1
HDAC4	0.014	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	-0.001	0.009	-9999	-0.16	1	1
SUMO1	0.014	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.015	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.023	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	0.029	0	-9999	-10000	0	0
SUMO1/HDAC1	0.028	0.013	-9999	-0.19	1	1
RANGAP1	0.014	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	0.031	0.027	-9999	-0.21	2	2
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.019	0	-9999	-10000	0	0
Ran/GTP	0.025	0	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.009	0.042	-9999	-0.34	4	4
UBE2I	0.014	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.029	0	-9999	-10000	0	0
NPC	0.008	0	-9999	-10000	0	0
PIAS2	0.012	0.026	-9999	-0.43	1	1
PIAS1	0.014	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.018	0	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.017	0.011	-9999	-10000	0	0
AP2	0.02	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0.019	0	-9999	-10000	0	0
CLTB	0.014	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.022	0	-9999	-10000	0	0
CD4	0.001	0.071	-9999	-0.41	8	8
CLTA	0.014	0	-9999	-10000	0	0
mol:GTP	0.001	0	-9999	-10000	0	0
ARFGAP1	0.01	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.011	0	-9999	-10000	0	0
ARF1/GTP	0.016	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.022	0	-9999	-10000	0	0
mol:Choline	0.011	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.014	0	-9999	-10000	0	0
DDEF1	0.011	0	-9999	-10000	0	0
ARF1/GDP	0.007	0	-9999	-10000	0	0
AP2M1	0.014	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0.015	0	-9999	-10000	0	0
Rac/GTP	0.011	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.024	0	-9999	-10000	0	0
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	0.022	0	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0.01	0	-9999	-10000	0	0
GGA3	0.014	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0.018	0	-9999	-10000	0	0
AP2A1	0.014	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.023	0	-9999	-10000	0	0
ARF1/GDP/Membrin	0.018	0	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0.018	0	-9999	-10000	0	0
CYTH2	0.014	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0.019	0	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0.01	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	0.025	0.032	-9999	-0.17	7	7
PLD2	0.011	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.01	0	-9999	-10000	0	0
PIP5K1A	0.011	0	-9999	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0.019	0.009	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0.011	0	-9999	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	0.01	0	-9999	-10000	0	0
GOSR2	0.013	0	-9999	-10000	0	0
USO1	0.009	0.041	-9999	-0.39	3	3
GBF1	0.013	0	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0.02	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.02	0.043	-9999	-0.23	8	8

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.019	0.019	-9999	-0.3	1	1
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	0.012	0.026	-9999	-0.43	1	1
NF kappa B2 p100/RelB	0.04	0.014	-9999	-0.19	1	1
NFKB1	0.014	0	-9999	-10000	0	0
MAP3K14	0.014	0	-9999	-10000	0	0
NF kappa B1 p50/RelB	0.02	0	-9999	-10000	0	0
RELB	0.014	0	-9999	-10000	0	0
NFKB2	0.014	0	-9999	-10000	0	0
NF kappa B2 p52/RelB	0.018	0	-9999	-10000	0	0
regulation of B cell activation	0.018	0	-9999	-10000	0	0

pid_entity	TCGA.HR.A2OH	TCGA.HR.A2OG	TCGA.GN.A26D	TCGA.GN.A26C
109_MAP3K5	0.045	-0.18	0.045	-0.18
47_PPARGC1A	0.014	-0.43	0.014	-0.43
105_BMP4	0.014	0.014	0.014	0.014
105_BMP6	0.014	0.014	0.014	0.014
105_BMP7	-0.31	0.014	0.014	0.014
105_BMP2	0.014	-0.31	0.014	0.014
131_RELN/VLDLR	-0.21	0.035	0.035	0.035
30_TGFB1/TGF beta receptor Type II	0.013	0.013	0.021	0.013
84_STAT5B	0.038	0.015	0.041	-0.21
84_STAT5A	0.038	0.015	0.041	-0.21