PARADIGM pathway analysis of mRNASeq expression data - Skin Cutaneous Melanoma (Metastatic)

Pathway.Name	Avg.Num.Perturbations
TCGA08_retinoblastoma	72
Ephrin A reverse signaling	61
TCGA08_p53	57
E-cadherin signaling events	53
TCR signaling in naïve CD8+ T cells	44
IL4-mediated signaling events	43
Signaling events regulated by Ret tyrosine kinase	43
IL23-mediated signaling events	42
Signaling events mediated by Stem cell factor receptor (c-Kit)	42
Syndecan-1-mediated signaling events	38

Pathway.Name	Significance.Ratio	Avg.Num.Perturbations	Total.Perturbations	Num.Entities	Min.Mean.Truth	Max.Mean.Truth	Min.Mean.Within	Max.Mean.Within	Min.Mean.Any	Max.Mean.Within.1
TCGA08_retinoblastoma	0.2707	72	579	8	-0.13	0.08	1000	-1000	-0.005	-1000
Ephrin A reverse signaling	0.2293	61	432	7	-0.097	0	1000	-1000	-0.007	-1000
TCGA08_p53	0.2143	57	405	7	-0.092	0.066	1000	-1000	-0.004	-1000
E-cadherin signaling events	0.1992	53	268	5	-0.13	0.014	1000	-1000	-0.007	-1000
TCR signaling in naïve CD8+ T cells	0.1654	44	4134	93	-0.25	0.02	1000	-1000	-0.039	-1000
IL4-mediated signaling events	0.1617	43	3993	91	-0.65	0.5	1000	-1000	-0.12	-1000
Signaling events regulated by Ret tyrosine kinase	0.1617	43	3560	82	-0.12	0.014	1000	-1000	-0.043	-1000
IL23-mediated signaling events	0.1579	42	2547	60	-0.39	0.014	1000	-1000	-0.068	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.1579	42	3316	78	-0.23	0.09	1000	-1000	-0.031	-1000
Syndecan-1-mediated signaling events	0.1429	38	1309	34	-0.11	0.014	1000	-1000	-0.015	-1000
IL12-mediated signaling events	0.1353	36	3170	87	-0.36	0.075	1000	-1000	-0.087	-1000
BCR signaling pathway	0.1316	35	3490	99	-0.2	0.014	1000	-1000	-0.048	-1000
Angiopoietin receptor Tie2-mediated signaling	0.1316	35	3142	88	-0.24	0.046	1000	-1000	-0.048	-1000
Glypican 1 network	0.1278	34	1650	48	-0.13	0.033	1000	-1000	-0.022	-1000
Wnt signaling	0.1278	34	240	7	-0.064	-0.025	1000	-1000	-0.009	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.1241	33	2306	68	-0.34	0.11	1000	-1000	-0.056	-1000
E-cadherin signaling in the nascent adherens junction	0.1128	30	2338	76	-0.13	0.024	1000	-1000	-0.046	-1000
LPA receptor mediated events	0.1090	29	2958	102	-0.12	0.014	1000	-1000	-0.046	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.1090	29	2208	74	-0.13	0.042	1000	-1000	-0.042	-1000
E-cadherin signaling in keratinocytes	0.1090	29	1262	43	-0.13	0.016	1000	-1000	-0.018	-1000
Noncanonical Wnt signaling pathway	0.1053	28	748	26	-0.064	0.014	1000	-1000	-0.016	-1000
p75(NTR)-mediated signaling	0.1053	28	3548	125	-0.11	0.039	1000	-1000	-0.044	-1000
BMP receptor signaling	0.1053	28	2316	81	-0.15	0.031	1000	-1000	-0.044	-1000
LPA4-mediated signaling events	0.1015	27	324	12	-0.087	0.013	1000	-1000	-0.009	-1000
Glucocorticoid receptor regulatory network	0.1015	27	3080	114	-0.36	0.25	1000	-1000	-0.041	-1000
FAS signaling pathway (CD95)	0.1015	27	1296	47	-0.077	0.044	1000	-1000	-0.015	-1000
EGFR-dependent Endothelin signaling events	0.1015	27	570	21	-0.088	0.02	1000	-1000	-0.034	-1000
Endothelins	0.0977	26	2551	96	-0.12	0.034	1000	-1000	-0.041	-1000
Signaling mediated by p38-alpha and p38-beta	0.0977	26	1158	44	-0.1	0.014	1000	-1000	-0.021	-1000
Glypican 2 network	0.0977	26	106	4	-0.025	-0.013	1000	-1000	-0.007	-1000
Caspase cascade in apoptosis	0.0940	25	1885	74	-0.082	0.044	1000	-1000	-0.016	-1000
Nectin adhesion pathway	0.0940	25	1611	63	-0.13	0.024	1000	-1000	-0.039	-1000
a4b1 and a4b7 Integrin signaling	0.0902	24	122	5	-0.031	-0.012	1000	-1000	-0.004	-1000
Integrins in angiogenesis	0.0902	24	2065	84	-0.13	0.022	1000	-1000	-0.044	-1000
IL27-mediated signaling events	0.0902	24	1239	51	-0.16	0.092	1000	-1000	-0.035	-1000
Thromboxane A2 receptor signaling	0.0865	23	2434	105	-0.088	0.024	1000	-1000	-0.035	-1000
HIF-1-alpha transcription factor network	0.0865	23	1809	76	-0.18	0.03	1000	-1000	-0.058	-1000
Calcium signaling in the CD4+ TCR pathway	0.0865	23	743	31	-0.17	0.014	1000	-1000	-0.04	-1000
Osteopontin-mediated events	0.0827	22	842	38	-0.06	0.014	1000	-1000	-0.025	-1000
Signaling events mediated by the Hedgehog family	0.0827	22	1178	52	-0.19	0.014	1000	-1000	-0.016	-1000
Syndecan-4-mediated signaling events	0.0827	22	1481	67	-0.084	0.014	1000	-1000	-0.024	-1000
TRAIL signaling pathway	0.0789	21	1036	48	-0.041	0.014	1000	-1000	-0.024	-1000
JNK signaling in the CD4+ TCR pathway	0.0752	20	345	17	-0.058	0.014	1000	-1000	-0.021	-1000
Reelin signaling pathway	0.0752	20	1134	56	-0.086	0.024	1000	-1000	-0.037	-1000
Ephrin B reverse signaling	0.0752	20	995	48	-0.064	0.014	1000	-1000	-0.021	-1000
EPHB forward signaling	0.0752	20	1752	85	-0.091	0.056	1000	-1000	-0.044	-1000
amb2 Integrin signaling	0.0714	19	1597	82	-0.068	0.018	1000	-1000	-0.027	-1000
Class IB PI3K non-lipid kinase events	0.0714	19	57	3	-0.015	-1000	1000	-1000	-0.005	-1000
Arf6 signaling events	0.0677	18	1165	62	-0.088	0.027	1000	-1000	-0.019	-1000
Signaling events mediated by PTP1B	0.0677	18	1430	76	-0.1	0.029	1000	-1000	-0.03	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0677	18	953	52	-0.084	0.021	1000	-1000	-0.02	-1000
Ras signaling in the CD4+ TCR pathway	0.0677	18	316	17	-0.043	0.027	1000	-1000	-0.016	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0639	17	795	45	-0.11	0.033	1000	-1000	-0.04	-1000
Effects of Botulinum toxin	0.0639	17	449	26	-0.078	0.014	1000	-1000	-0.012	-1000
Syndecan-2-mediated signaling events	0.0602	16	1168	69	-0.08	0.019	1000	-1000	-0.013	-1000
S1P5 pathway	0.0564	15	268	17	-0.068	0.028	1000	-1000	-0.011	-1000
IL2 signaling events mediated by PI3K	0.0564	15	887	58	-0.07	0.029	1000	-1000	-0.027	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0564	15	1908	120	-0.12	0.11	1000	-1000	-0.038	-1000
S1P4 pathway	0.0564	15	382	25	-0.068	0.02	1000	-1000	-0.016	-1000
PDGFR-alpha signaling pathway	0.0526	14	657	44	-0.025	0.018	1000	-1000	-0.021	-1000
IL2 signaling events mediated by STAT5	0.0526	14	315	22	-0.067	0.014	1000	-1000	-0.025	-1000
Class I PI3K signaling events	0.0526	14	1039	73	-0.12	0.026	1000	-1000	-0.024	-1000
Plasma membrane estrogen receptor signaling	0.0526	14	1252	86	-0.1	0.028	1000	-1000	-0.045	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0489	13	1129	85	-0.048	0.014	1000	-1000	-0.044	-1000
Fc-epsilon receptor I signaling in mast cells	0.0489	13	1347	97	-0.073	0.024	1000	-1000	-0.047	-1000
IFN-gamma pathway	0.0489	13	938	68	-0.085	0.024	1000	-1000	-0.048	-1000
Ceramide signaling pathway	0.0489	13	1015	76	-0.088	0.045	1000	-1000	-0.015	-1000
S1P1 pathway	0.0489	13	480	36	-0.094	0.014	1000	-1000	-0.031	-1000
Signaling mediated by p38-gamma and p38-delta	0.0489	13	195	15	-0.026	0.014	1000	-1000	-0.011	-1000
Rapid glucocorticoid signaling	0.0489	13	269	20	-0.069	0.014	1000	-1000	-0.008	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0451	12	471	37	-0.031	0.026	1000	-1000	-0.016	-1000
Visual signal transduction: Rods	0.0451	12	654	52	-0.046	0.014	1000	-1000	-0.04	-1000
ErbB2/ErbB3 signaling events	0.0414	11	751	65	-0.053	0.02	1000	-1000	-0.036	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0414	11	315	28	-0.068	0.024	1000	-1000	-0.015	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0414	11	617	54	-0.086	0.024	1000	-1000	-0.047	-1000
FOXA2 and FOXA3 transcription factor networks	0.0414	11	533	46	-0.24	0.015	1000	-1000	-0.077	-1000
IL1-mediated signaling events	0.0414	11	736	62	-0.048	0.05	1000	-1000	-0.051	-1000
S1P3 pathway	0.0414	11	477	42	-0.066	0.023	1000	-1000	-0.025	-1000
Cellular roles of Anthrax toxin	0.0376	10	410	39	-0.039	0.014	1000	-1000	-0.014	-1000
Paxillin-dependent events mediated by a4b1	0.0376	10	394	36	-0.031	0.034	1000	-1000	-0.03	-1000
Regulation of p38-alpha and p38-beta	0.0376	10	578	54	-0.082	0.035	1000	-1000	-0.033	-1000
Nongenotropic Androgen signaling	0.0376	10	551	52	-0.068	0.03	1000	-1000	-0.025	-1000
IGF1 pathway	0.0376	10	577	57	-0.026	0.028	1000	-1000	-0.045	-1000
Regulation of nuclear SMAD2/3 signaling	0.0338	9	1240	136	-0.17	0.044	1000	-1000	-0.023	-1000
Coregulation of Androgen receptor activity	0.0338	9	722	76	-0.13	0.029	1000	-1000	-0.02	-1000
ErbB4 signaling events	0.0338	9	685	69	-0.15	0.097	1000	-1000	-0.045	-1000
Signaling events mediated by HDAC Class III	0.0338	9	370	40	-0.12	0.025	1000	-1000	-0.008	-1000
ceramide signaling pathway	0.0338	9	463	49	-0.058	0.02	1000	-1000	-0.016	-1000
Atypical NF-kappaB pathway	0.0338	9	296	31	-0.067	0.024	1000	-1000	-0.007	-1000
IL6-mediated signaling events	0.0338	9	700	75	-0.031	0.048	1000	-1000	-0.031	-1000
Visual signal transduction: Cones	0.0301	8	321	38	-0.03	0.013	1000	-1000	-0.009	-1000
Hedgehog signaling events mediated by Gli proteins	0.0301	8	540	65	-0.067	0.053	1000	-1000	-0.039	-1000
Presenilin action in Notch and Wnt signaling	0.0301	8	516	61	-0.089	0.042	1000	-1000	-0.026	-1000
Retinoic acid receptors-mediated signaling	0.0301	8	481	58	-0.06	0.028	1000	-1000	-0.039	-1000
Syndecan-3-mediated signaling events	0.0301	8	296	35	-0.077	0.039	1000	-1000	-0.026	-1000
Canonical Wnt signaling pathway	0.0301	8	458	51	-0.089	0.044	1000	-1000	-0.031	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0301	8	279	33	-0.13	0.038	1000	-1000	-0.015	-1000
Regulation of Androgen receptor activity	0.0301	8	628	70	-0.13	0.023	1000	-1000	-0.039	-1000
PLK2 and PLK4 events	0.0263	7	21	3	0.004	0.007	1000	-1000	-0.002	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0263	7	621	83	-0.062	0.044	1000	-1000	-0.019	-1000
TCGA08_rtk_signaling	0.0263	7	192	26	-0.041	0.034	1000	-1000	-0.008	-1000
Regulation of Telomerase	0.0263	7	795	102	-0.089	0.04	1000	-1000	-0.069	-1000
Insulin Pathway	0.0263	7	540	74	-0.07	0.034	1000	-1000	-0.043	-1000
Signaling events mediated by PRL	0.0263	7	268	34	-0.091	0.027	1000	-1000	-0.017	-1000
FOXM1 transcription factor network	0.0263	7	387	51	-0.14	0.13	1000	-1000	-0.13	-1000
Aurora B signaling	0.0263	7	486	67	-0.095	0.03	1000	-1000	-0.029	-1000
EPO signaling pathway	0.0226	6	359	55	-0.025	0.034	1000	-1000	-0.04	-1000
PDGFR-beta signaling pathway	0.0188	5	542	97	-0.076	0.041	1000	-1000	-0.039	-1000
p38 MAPK signaling pathway	0.0188	5	230	44	-0.036	0.026	1000	-1000	-0.037	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0150	4	151	34	-0.019	0.015	1000	-1000	-0.016	-1000
BARD1 signaling events	0.0150	4	249	57	-0.022	0.045	1000	-1000	-0.021	-1000
Arf6 downstream pathway	0.0150	4	197	43	-0.017	0.023	1000	-1000	-0.016	-1000
Aurora C signaling	0.0150	4	32	7	-0.006	0.01	1000	-1000	-0.009	-1000
Insulin-mediated glucose transport	0.0150	4	134	32	-0.055	0.025	1000	-1000	-0.018	-1000
mTOR signaling pathway	0.0150	4	230	53	-0.013	0.023	1000	-1000	-0.033	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0150	4	500	125	-0.058	0.046	1000	-1000	-0.053	-1000
Canonical NF-kappaB pathway	0.0113	3	141	39	-0.025	0.054	1000	-1000	-0.039	-1000
Circadian rhythm pathway	0.0113	3	71	22	-0.016	0.037	1000	-1000	-0.019	-1000
Aurora A signaling	0.0113	3	191	60	-0.053	0.036	1000	-1000	-0.009	-1000
FoxO family signaling	0.0113	3	229	64	-0.2	0.11	1000	-1000	-0.039	-1000
VEGFR1 specific signals	0.0113	3	172	56	-0.017	0.034	1000	-1000	-0.022	-1000
Signaling events mediated by HDAC Class II	0.0075	2	214	75	-0.05	0.036	1000	-1000	-0.023	-1000
Signaling events mediated by HDAC Class I	0.0075	2	289	104	-0.027	0.044	1000	-1000	-0.021	-1000
Arf6 trafficking events	0.0075	2	147	71	-0.033	0.032	1000	-1000	-0.028	-1000
PLK1 signaling events	0.0038	1	138	85	-0.007	0.032	1000	-1000	-0.019	-1000
Class I PI3K signaling events mediated by Akt	0.0038	1	100	68	-0.055	0.041	1000	-1000	-0.022	-1000
HIF-2-alpha transcription factor network	0.0038	1	71	43	-0.14	0.14	1000	-1000	-0.051	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	13	23	0.004	0.04	1000	-1000	-0.019	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	8	27	-0.001	0.033	1000	-1000	-0.027	-1000
Arf1 pathway	0.0000	0	30	54	-0.001	0.024	1000	-1000	-0.01	-1000
Alternative NF-kappaB pathway	0.0000	0	3	13	0	0.04	1000	-1000	-0.004	-1000
Total	NA	2205	122496	7203	-12	-1000	131000	-131000	-3.9	-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	-0.064	0.15	-10000	0	-0.34	57	57
CDKN2C	0.016	0.028	-10000	0	-0.39	1	1
CDKN2A	-0.13	0.18	-10000	0	-0.36	100	100
CCND2	0.07	0.12	0.23	82	-0.11	3	85
RB1	-0.075	0.13	-10000	0	-0.25	82	82
CDK4	0.08	0.14	0.26	84	-10000	0	84
CDK6	0.077	0.14	0.26	82	-0.14	6	88
G1/S progression	0.075	0.13	0.25	82	-10000	0	82

×

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	-0.071	0.14	-9999	-0.26	86	86
EFNA5	-0.028	0.12	-9999	-0.39	27	27
FYN	-0.059	0.12	-9999	-0.24	76	76
neuron projection morphogenesis	-0.071	0.14	-9999	-0.26	86	86
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.071	0.14	-9999	-0.26	86	86
EPHA5	-0.097	0.18	-9999	-0.4	71	71

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.092	0.14	-10000	0	-0.26	100	100
TP53	-0.043	0.066	0.2	1	-0.13	76	77
Senescence	-0.042	0.066	0.2	1	-0.13	76	77
Apoptosis	-0.042	0.066	0.2	1	-0.13	76	77
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.066	0.091	0.21	71	-0.17	2	73
MDM4	0.012	0.027	-10000	0	-0.42	1	1

×

E-cadherin 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
E-cadherin/beta catenin-gamma catenin	-0.061	0.12	-9999	-0.24	77	77
E-cadherin/beta catenin	-0.079	0.14	-9999	-0.27	92	92
CTNNB1	0.014	0	-9999	-10000	0	0
JUP	0.005	0.051	-9999	-0.3	7	7
CDH1	-0.13	0.2	-9999	-0.39	92	92

×

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	0.29	-10000	0	-0.57	69	69
FYN	-0.19	0.41	-10000	0	-0.76	74	74
LAT/GRAP2/SLP76	-0.17	0.29	-10000	0	-0.59	74	74
IKBKB	0.014	0	-10000	0	-10000	0	0
AKT1	-0.095	0.24	-10000	0	-0.45	72	72
B2M	0.007	0.047	-10000	0	-0.43	3	3
IKBKG	-0.018	0.074	-10000	0	-0.14	58	58
MAP3K8	0	0.07	-10000	0	-0.33	11	11
mol:Ca2+	-0.013	0.021	-10000	0	-0.055	26	26
integrin-mediated signaling pathway	0.009	0.047	-10000	0	-0.21	11	11
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.16	0.37	-10000	0	-0.7	73	73
TRPV6	-0.014	0.064	-10000	0	-0.26	17	17
CD28	-0.017	0.1	-10000	0	-0.37	21	21
SHC1	-0.18	0.4	-10000	0	-0.73	76	76
receptor internalization	-0.21	0.45	-10000	0	-0.82	75	75
PRF1	-0.22	0.49	-10000	0	-1.2	50	50
KRAS	0.013	0.016	-10000	0	-0.25	1	1
GRB2	0.014	0	-10000	0	-10000	0	0
COT/AKT1	-0.068	0.19	-10000	0	-0.36	69	69
LAT	-0.19	0.4	-10000	0	-0.77	73	73
EntrezGene:6955	-0.001	0.004	-10000	0	-10000	0	0
CD3D	-0.069	0.16	-10000	0	-0.37	57	57
CD3E	-0.071	0.17	-10000	0	-0.38	57	57
CD3G	-0.076	0.17	-10000	0	-0.37	62	62
RASGRP2	-0.009	0.042	-10000	0	-0.19	10	10
RASGRP1	-0.1	0.25	-10000	0	-0.49	72	72
HLA-A	0.002	0.066	-10000	0	-0.43	6	6
RASSF5	-0.002	0.079	-10000	0	-0.37	11	11
RAP1A/GTP/RAPL	0.009	0.047	-10000	0	-0.21	11	11
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	-0.01	0.07	-10000	0	-0.12	61	61
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.069	0.11	-10000	0	-0.25	62	62
PRKCA	-0.068	0.13	-10000	0	-0.28	68	68
GRAP2	-0.012	0.1	-10000	0	-0.39	17	17
mol:IP3	-0.12	0.21	0.14	11	-0.43	72	83
EntrezGene:6957	-0.002	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.22	0.48	-10000	0	-0.9	70	70
ORAI1	0.015	0.047	0.16	17	-0.29	2	19
CSK	-0.19	0.41	-10000	0	-0.75	76	76
B7 family/CD28	-0.19	0.42	-10000	0	-0.8	71	71
CHUK	0.012	0.027	-10000	0	-0.42	1	1
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.24	0.5	-10000	0	-0.91	77	77
PTPN6	-0.2	0.43	-10000	0	-0.78	76	76
VAV1	-0.19	0.41	-10000	0	-0.76	76	76
Monovalent TCR/CD3	-0.15	0.34	-10000	0	-0.62	69	69
CBL	0.014	0	-10000	0	-10000	0	0
LCK	-0.22	0.47	-10000	0	-0.83	78	78
PAG1	-0.19	0.41	-10000	0	-0.76	77	77
RAP1A	0.014	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.24	0.51	-10000	0	-0.89	78	78
CD80	-0.018	0.11	-10000	0	-0.38	21	21
CD86	-0.015	0.11	-10000	0	-0.43	17	17
PDK1/CARD11/BCL10/MALT1	-0.085	0.13	-10000	0	-0.29	70	70
HRAS	0.014	0	-10000	0	-10000	0	0
GO:0035030	-0.14	0.32	-10000	0	-0.62	71	71
CD8A	-0.087	0.18	-10000	0	-0.38	69	69
CD8B	-0.096	0.18	-10000	0	-0.39	73	73
PTPRC	-0.053	0.15	-10000	0	-0.37	46	46
PDK1/PKC theta	-0.12	0.3	-10000	0	-0.57	72	72
CSK/PAG1	-0.18	0.4	-10000	0	-0.78	70	70
SOS1	0.014	0	-10000	0	-10000	0	0
peptide-MHC class I	0.007	0.062	-10000	0	-0.33	8	8
GRAP2/SLP76	-0.17	0.38	-10000	0	-0.71	73	73
STIM1	0.009	0.021	-10000	0	-10000	0	0
RAS family/GTP	-0.015	0.095	-10000	0	-0.18	57	57
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.24	0.52	-10000	0	-0.93	75	75
mol:DAG	-0.11	0.18	-10000	0	-0.38	74	74
RAP1A/GDP	-0.003	0.031	-10000	0	-0.059	45	45
PLCG1	0.014	0	-10000	0	-10000	0	0
CD247	-0.052	0.15	-10000	0	-0.37	46	46
cytotoxic T cell degranulation	-0.2	0.45	-10000	0	-1	55	55
RAP1A/GTP	-0.006	0.014	-10000	0	-0.069	10	10
mol:PI-3-4-5-P3	-0.12	0.29	-10000	0	-0.55	72	72
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.16	0.28	0.15	11	-0.58	72	83
NRAS	0.014	0	-10000	0	-10000	0	0
ZAP70	-0.063	0.15	-10000	0	-0.34	57	57
GRB2/SOS1	0.02	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.17	0.28	-10000	0	-0.57	74	74
MALT1	0.01	0.037	-10000	0	-0.42	2	2
TRAF6	0.014	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.12	0.22	-10000	0	-0.45	79	79
CARD11	-0.059	0.15	-10000	0	-0.37	51	51
PRKCB	-0.079	0.15	-10000	0	-0.3	73	73
PRKCE	-0.066	0.13	-10000	0	-0.27	68	68
PRKCQ	-0.16	0.35	-10000	0	-0.68	72	72
LCP2	-0.011	0.1	-10000	0	-0.42	15	15
BCL10	0.013	0.016	-10000	0	-0.25	1	1
regulation of survival gene product expression	-0.076	0.2	-10000	0	-0.38	71	71
IKK complex	-0.006	0.064	-10000	0	-0.11	56	56
RAS family/GDP	-0.008	0.013	-10000	0	-10000	0	0
MAP3K14	-0.045	0.14	-10000	0	-0.27	67	67
PDPK1	-0.087	0.22	-10000	0	-0.43	70	70
TCR/CD3/MHC I/CD8/Fyn	-0.25	0.53	-10000	0	-0.99	73	73

×

IL4-mediated signaling events

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
BCL2L1	-0.44	0.48	-10000	0	-1.2	63	63
STAT6 (cleaved dimer)	-0.51	0.5	-10000	0	-1.1	97	97
IGHG1	-0.15	0.15	-10000	0	-0.34	57	57
IGHG3	-0.43	0.46	-10000	0	-1	83	83
AKT1	-0.28	0.36	-10000	0	-0.86	56	56
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.27	0.42	-10000	0	-0.98	52	52
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.3	0.39	-10000	0	-0.93	53	53
THY1	-0.44	0.48	-10000	0	-1.2	63	63
MYB	-0.004	0.081	-10000	0	-0.35	13	13
HMGA1	0.012	0.023	-10000	0	-0.25	2	2
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.36	0.43	-10000	0	-0.87	80	80
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.3	0.42	-10000	0	-1	50	50
SP1	0.018	0.012	-10000	0	-10000	0	0
INPP5D	-0.011	0.097	-10000	0	-0.39	16	16
SOCS5	0.026	0.016	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.47	0.52	-10000	0	-1.1	84	84
SOCS1	-0.3	0.32	-10000	0	-0.72	74	74
SOCS3	-0.29	0.37	-10000	0	-0.92	49	49
FCER2	-0.49	0.55	-10000	0	-1.2	82	82
PARP14	0.007	0.038	-10000	0	-0.42	2	2
CCL17	-0.5	0.55	-10000	0	-1.3	74	74
GRB2	0.014	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.23	0.31	-10000	0	-0.77	46	46
T cell proliferation	-0.46	0.52	-10000	0	-1.2	71	71
IL4R/JAK1	-0.44	0.48	-10000	0	-1.1	68	68
EGR2	-0.48	0.52	-10000	0	-1.2	64	64
JAK2	-0.024	0.067	-10000	0	-0.42	6	6
JAK3	-0.004	0.082	-10000	0	-0.34	14	14
PIK3R1	0.01	0.037	-10000	0	-0.42	2	2
JAK1	0.006	0.011	-10000	0	-10000	0	0
COL1A2	-0.18	0.29	-10000	0	-1.4	10	10
CCL26	-0.45	0.48	-10000	0	-1.1	64	64
IL4R	-0.48	0.52	-10000	0	-1.2	66	66
PTPN6	-0.002	0.099	-10000	0	-0.37	17	17
IL13RA2	-0.65	0.61	-10000	0	-1.3	114	114
IL13RA1	-0.016	0.04	-10000	0	-0.46	1	1
IRF4	-0.31	0.52	-10000	0	-1.3	50	50
ARG1	-0.13	0.16	-10000	0	-0.66	11	11
CBL	-0.33	0.4	-10000	0	-0.82	79	79
GTF3A	0.018	0.013	-10000	0	-10000	0	0
PIK3CA	0.008	0.048	-10000	0	-0.38	4	4
IL13RA1/JAK2	-0.025	0.06	-10000	0	-0.3	7	7
IRF4/BCL6	-0.27	0.48	-10000	0	-1.2	50	50
CD40LG	-0.058	0.14	-10000	0	-0.34	50	50
MAPK14	-0.33	0.41	-10000	0	-0.84	79	79
mitosis	-0.26	0.33	-10000	0	-0.79	56	56
STAT6	-0.52	0.6	-10000	0	-1.2	82	82
SPI1	-0.006	0.091	-10000	0	-0.4	13	13
RPS6KB1	-0.25	0.32	-10000	0	-0.75	56	56
STAT6 (dimer)	-0.52	0.6	-10000	0	-1.2	82	82
STAT6 (dimer)/PARP14	-0.5	0.54	-10000	0	-1.2	83	83
mast cell activation	0.012	0.012	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.31	0.43	-10000	0	-1	54	54
FRAP1	-0.28	0.36	-10000	0	-0.86	56	56
LTA	-0.52	0.58	-10000	0	-1.4	71	71
FES	0.002	0.069	-10000	0	-0.42	7	7
T-helper 1 cell differentiation	0.5	0.56	1.2	82	-10000	0	82
CCL11	-0.46	0.49	-10000	0	-1.2	69	69
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.3	0.42	-10000	0	-0.96	57	57
IL2RG	-0.049	0.15	-10000	0	-0.37	44	44
IL10	-0.47	0.53	-10000	0	-1.2	68	68
IRS1	-0.009	0.095	-10000	0	-0.41	14	14
IRS2	0.012	0.027	-10000	0	-0.42	1	1
IL4	-0.11	0.11	-10000	0	-10000	0	0
IL5	-0.45	0.48	-10000	0	-1.1	70	70
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.36	0.37	-10000	0	-0.87	65	65
COL1A1	-0.2	0.32	-10000	0	-1.5	12	12
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.45	0.5	-10000	0	-1.2	62	62
IL2R gamma/JAK3	-0.037	0.13	-10000	0	-0.32	44	44
TFF3	-0.56	0.58	-10000	0	-1.3	89	89
ALOX15	-0.45	0.48	-10000	0	-1.2	64	64
MYBL1	0.007	0.053	-10000	0	-0.42	4	4
T-helper 2 cell differentiation	-0.41	0.46	-10000	0	-0.99	77	77
SHC1	0.014	0	-10000	0	-10000	0	0
CEBPB	0.015	0.007	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.29	0.39	-10000	0	-0.93	51	51
mol:PI-3-4-5-P3	-0.28	0.36	-10000	0	-0.86	56	56
PI3K	-0.3	0.4	-10000	0	-0.95	56	56
DOK2	-0.004	0.086	-10000	0	-0.42	11	11
ETS1	0.024	0.019	-10000	0	-0.21	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.21	0.29	-10000	0	-0.74	43	43
ITGB3	-0.53	0.58	-10000	0	-1.3	77	77
PIGR	-0.49	0.53	-10000	0	-1.2	74	74
IGHE	0.039	0.042	0.22	4	-10000	0	4
MAPKKK cascade	-0.21	0.28	-10000	0	-0.72	43	43
BCL6	0.016	0.005	-10000	0	-10000	0	0
OPRM1	-0.45	0.48	-10000	0	-1.2	63	63
RETNLB	-0.45	0.48	-10000	0	-1.2	63	63
SELP	-0.53	0.58	-10000	0	-1.3	81	81
AICDA	-0.44	0.46	-10000	0	-1.1	65	65

×

Signaling events regulated by Ret tyrosine kinase

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.011	0.043	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.074	0.11	-9999	-0.26	42	42
JUN	-0.05	0.12	-9999	-0.36	18	18
HRAS	0.014	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.083	0.14	-9999	-0.25	87	87
RAP1A	0.014	0	-9999	-10000	0	0
FRS2	0.013	0.016	-9999	-0.25	1	1
RAP1A/GDP	0.01	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.081	0.14	-9999	-0.25	86	86
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	-0.077	0.12	-9999	-0.24	79	79
RHOA	0.014	0	-9999	-10000	0	0
RAP1A/GTP	-0.07	0.12	-9999	-0.22	88	88
GRB7	-0.013	0.077	-9999	-0.26	24	24
RET51/GFRalpha1/GDNF	-0.08	0.14	-9999	-0.25	85	85
MAPKKK cascade	-0.079	0.11	-9999	-0.23	71	71
BCAR1	0.01	0.037	-9999	-0.42	2	2
RET9/GFRalpha1/GDNF/IRS1	-0.089	0.13	-9999	-0.25	90	90
lamellipodium assembly	-0.073	0.1	-9999	-0.22	73	73
RET51/GFRalpha1/GDNF/SHC	-0.08	0.14	-9999	-0.25	85	85
PIK3CA	0.008	0.048	-9999	-0.38	4	4
RET9/GFRalpha1/GDNF/SHC	-0.077	0.12	-9999	-0.24	79	79
RET9/GFRalpha1/GDNF/Shank3	-0.08	0.13	-9999	-0.25	81	81
MAPK3	-0.064	0.11	-9999	-0.2	88	88
DOK1	0.011	0.031	-9999	-0.33	2	2
DOK6	-0.037	0.12	-9999	-0.3	43	43
PXN	0.014	0	-9999	-10000	0	0
neurite development	-0.061	0.12	-9999	-0.28	32	32
DOK5	-0.06	0.13	-9999	-0.28	66	66
GFRA1	-0.083	0.16	-9999	-0.32	76	76
MAPK8	-0.057	0.13	-9999	-0.23	74	74
HRAS/GTP	-0.076	0.13	-9999	-0.26	73	73
tube development	-0.069	0.12	-9999	-0.23	81	81
MAPK1	-0.064	0.11	-9999	-0.25	38	38
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.057	0.11	-9999	-0.23	68	68
Rac1/GDP	0.01	0	-9999	-10000	0	0
SRC	0.012	0.027	-9999	-0.42	1	1
PDLIM7	0.014	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.093	0.15	-9999	-0.25	100	100
SHC1	0.014	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.082	0.14	-9999	-0.25	88	88
RET51/GFRalpha1/GDNF/Dok5	-0.12	0.15	-9999	-0.27	112	112
PRKCA	-0.006	0.086	-9999	-0.38	13	13
HRAS/GDP	0.01	0	-9999	-10000	0	0
CREB1	-0.059	0.13	-9999	-0.26	69	69
PIK3R1	0.01	0.037	-9999	-0.42	2	2
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.059	0.12	-9999	-0.24	69	69
RET51/GFRalpha1/GDNF/Grb7	-0.092	0.14	-9999	-0.26	91	91
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.006	0.079	-9999	-0.3	17	17
DOK4	0.009	0.046	-9999	-0.42	3	3
JNK cascade	-0.049	0.12	-9999	-0.35	18	18
RET9/GFRalpha1/GDNF/FRS2	-0.077	0.12	-9999	-0.24	79	79
SHANK3	0.009	0.046	-9999	-0.42	3	3
RASA1	0.01	0.037	-9999	-0.42	2	2
NCK1	0.014	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.057	0.11	-9999	-0.23	68	68
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.06	0.12	-9999	-0.24	71	71
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.063	0.13	-9999	-0.24	74	74
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.059	0.12	-9999	-0.24	71	71
PI3K	-0.082	0.17	-9999	-0.32	73	73
SOS1	0.014	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.068	0.12	-9999	-0.23	81	81
GRB10	0.007	0.053	-9999	-0.42	4	4
activation of MAPKK activity	-0.068	0.14	-9999	-0.27	69	69
RET51/GFRalpha1/GDNF/FRS2	-0.08	0.14	-9999	-0.25	85	85
GAB1	0.01	0.037	-9999	-0.42	2	2
IRS1	-0.009	0.095	-9999	-0.41	14	14
IRS2	0.012	0.027	-9999	-0.42	1	1
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.062	0.13	-9999	-0.24	71	71
RET51/GFRalpha1/GDNF/PKC alpha	-0.089	0.15	-9999	-0.26	91	91
GRB2	0.014	0	-9999	-10000	0	0
PRKACA	0.014	0	-9999	-10000	0	0
GDNF	-0.084	0.16	-9999	-0.35	70	70
RAC1	0.014	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.091	0.14	-9999	-0.26	95	95
Rac1/GTP	-0.085	0.12	-9999	-0.26	73	73
RET9/GFRalpha1/GDNF	-0.094	0.14	-9999	-0.22	122	122
GFRalpha1/GDNF	-0.11	0.16	-9999	-0.27	122	122

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.29	0.52	-10000	0	-1.1	60	60
IL23A	-0.3	0.54	-10000	0	-1.1	66	66
NF kappa B1 p50/RelA/I kappa B alpha	-0.34	0.51	-10000	0	-1.1	65	65
positive regulation of T cell mediated cytotoxicity	-0.35	0.62	-10000	0	-1.3	67	67
ITGA3	-0.32	0.55	-10000	0	-1.1	71	71
IL17F	-0.18	0.34	-10000	0	-0.71	60	60
IL12B	-0.007	0.058	-10000	0	-0.26	9	9
STAT1 (dimer)	-0.33	0.59	-10000	0	-1.2	67	67
CD4	-0.29	0.52	-10000	0	-1.1	60	60
IL23	-0.29	0.52	-10000	0	-1.1	66	66
IL23R	-0.028	0.09	-10000	0	-10000	0	0
IL1B	-0.33	0.58	-10000	0	-1.2	65	65
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.31	0.55	-10000	0	-1.2	64	64
TYK2	0.004	0.023	-10000	0	-10000	0	0
STAT4	-0.031	0.12	-10000	0	-0.35	33	33
STAT3	0.014	0	-10000	0	-10000	0	0
IL18RAP	-0.036	0.12	-10000	0	-0.33	35	35
IL12RB1	-0.05	0.15	-10000	0	-0.43	35	35
PIK3CA	0.008	0.048	-10000	0	-0.38	4	4
IL12Rbeta1/TYK2	-0.032	0.11	-10000	0	-0.31	35	35
IL23R/JAK2	-0.035	0.12	-10000	0	-10000	0	0
positive regulation of chronic inflammatory response	-0.35	0.62	-10000	0	-1.3	67	67
natural killer cell activation	0.004	0.008	0.03	1	-10000	0	1
JAK2	-0.004	0.07	-10000	0	-0.41	6	6
PIK3R1	0.01	0.037	-10000	0	-0.42	2	2
NFKB1	0.012	0.004	-10000	0	-10000	0	0
RELA	0.012	0.004	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.28	0.48	-10000	0	-1	66	66
ALOX12B	-0.29	0.51	-10000	0	-1.1	61	61
CXCL1	-0.34	0.56	-10000	0	-1.2	71	71
T cell proliferation	-0.35	0.62	-10000	0	-1.3	67	67
NFKBIA	0.012	0.004	-10000	0	-10000	0	0
IL17A	-0.13	0.27	-10000	0	-0.54	60	60
PI3K	-0.31	0.56	-10000	0	-1.2	64	64
IFNG	-0.031	0.056	-10000	0	-0.12	58	58
STAT3 (dimer)	-0.33	0.49	-10000	0	-1.1	64	64
IL18R1	-0.031	0.12	-10000	0	-0.36	29	29
IL23/IL23R/JAK2/TYK2/SOCS3	-0.17	0.34	-10000	0	-0.69	59	59
IL18/IL18R	-0.055	0.15	-10000	0	-0.33	48	48
macrophage activation	-0.016	0.019	-10000	0	-0.043	67	67
TNF	-0.32	0.56	-10000	0	-1.2	63	63
STAT3/STAT4	-0.32	0.56	-10000	0	-1.2	66	66
STAT4 (dimer)	-0.34	0.6	-10000	0	-1.2	68	68
IL18	-0.031	0.12	-10000	0	-0.37	28	28
IL19	-0.29	0.51	-10000	0	-1.1	60	60
STAT5A (dimer)	-0.33	0.59	-10000	0	-1.2	66	66
STAT1	0.01	0.037	-10000	0	-0.42	2	2
SOCS3	0	0.076	-10000	0	-0.4	9	9
CXCL9	-0.39	0.63	-10000	0	-1.3	73	73
MPO	-0.3	0.53	-10000	0	-1.1	65	65
positive regulation of humoral immune response	-0.35	0.62	-10000	0	-1.3	67	67
IL23/IL23R/JAK2/TYK2	-0.39	0.73	-10000	0	-1.5	66	66
IL6	-0.3	0.53	-10000	0	-1.1	62	62
STAT5A	0.01	0.037	-10000	0	-0.42	2	2
IL2	-0.004	0.035	-10000	0	-0.24	4	4
positive regulation of tyrosine phosphorylation of STAT protein	0.004	0.008	0.03	1	-10000	0	1
CD3E	-0.33	0.59	-10000	0	-1.3	61	61
keratinocyte proliferation	-0.35	0.62	-10000	0	-1.3	67	67
NOS2	-0.31	0.53	-10000	0	-1.1	65	65

×

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

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
MAP4K1	-0.072	0.18	-10000	0	-0.38	58	58
CRKL	-0.066	0.18	-10000	0	-0.39	56	56
HRAS	-0.06	0.16	-10000	0	-0.33	61	61
mol:PIP3	-0.067	0.16	-10000	0	-0.36	58	58
SPRED1	0.004	0.064	-10000	0	-0.42	6	6
SPRED2	0.014	0	-10000	0	-10000	0	0
GAB1	-0.073	0.19	-10000	0	-0.41	57	57
FOXO3	-0.054	0.16	-10000	0	-0.35	55	55
AKT1	-0.063	0.17	-10000	0	-0.38	55	55
BAD	-0.054	0.16	-10000	0	-0.35	55	55
megakaryocyte differentiation	-0.081	0.18	0.18	4	-0.4	59	63
GSK3B	-0.054	0.16	-10000	0	-0.35	55	55
RAF1	-0.044	0.13	-10000	0	-0.27	59	59
SHC1	0.014	0	-10000	0	-10000	0	0
STAT3	-0.072	0.18	0.18	8	-0.4	58	66
STAT1	-0.18	0.41	-10000	0	-0.93	58	58
HRAS/SPRED1	-0.048	0.14	-10000	0	-0.27	61	61
cell proliferation	-0.073	0.18	0.18	7	-0.39	60	67
PIK3CA	0.008	0.049	-10000	0	-0.38	4	4
TEC	-0.003	0.082	-10000	0	-0.42	10	10
RPS6KB1	-0.07	0.18	-10000	0	-0.4	58	58
HRAS/SPRED2	-0.044	0.14	-10000	0	-0.27	59	59
LYN/TEC/p62DOK	-0.069	0.18	-10000	0	-0.39	58	58
MAPK3	-0.023	0.1	-10000	0	-0.19	59	59
STAP1	-0.11	0.19	-10000	0	-0.42	62	62
GRAP2	-0.012	0.1	-10000	0	-0.39	17	17
JAK2	-0.15	0.35	-10000	0	-0.79	58	58
STAT1 (dimer)	-0.18	0.4	-10000	0	-0.91	58	58
mol:Gleevec	0.002	0.007	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.079	0.18	-10000	0	-0.4	57	57
actin filament polymerization	-0.075	0.18	0.18	7	-0.39	58	65
LYN	0.009	0.046	-10000	0	-0.42	3	3
STAP1/STAT5A (dimer)	-0.14	0.26	-10000	0	-0.56	63	63
PIK3R1	0.01	0.038	-10000	0	-0.42	2	2
CBL/CRKL/GRB2	-0.048	0.16	-10000	0	-0.35	56	56
PI3K	-0.06	0.18	-10000	0	-0.39	57	57
PTEN	0.007	0.053	-10000	0	-0.42	4	4
SCF/KIT/EPO/EPOR	-0.21	0.48	-10000	0	-1.2	52	52
MAPK8	-0.074	0.19	0.18	6	-0.4	60	66
STAT3 (dimer)	-0.07	0.18	0.18	8	-0.39	58	66
positive regulation of transcription	-0.017	0.085	-10000	0	-0.16	56	56
mol:GDP	-0.069	0.17	-10000	0	-0.34	63	63
PIK3C2B	-0.072	0.18	0.18	8	-0.4	58	66
CBL/CRKL	-0.055	0.17	-10000	0	-0.37	56	56
FER	-0.075	0.19	0.18	7	-0.4	60	67
SH2B3	-0.074	0.18	0.18	7	-0.4	58	65
PDPK1	-0.058	0.15	-10000	0	-0.34	56	56
SNAI2	-0.079	0.18	-10000	0	-0.41	58	58
positive regulation of cell proliferation	-0.13	0.31	-10000	0	-0.69	58	58
KITLG	-0.004	0.075	-10000	0	-0.39	9	9
cell motility	-0.13	0.31	-10000	0	-0.69	58	58
PTPN6	-0.008	0.1	-10000	0	-0.38	17	17
EPOR	-0.03	0.13	-10000	0	-10000	0	0
STAT5A (dimer)	-0.11	0.26	-10000	0	-0.58	58	58
SOCS1	0.001	0.065	-10000	0	-0.32	10	10
cell migration	0.09	0.18	0.4	62	-10000	0	62
SOS1	0.014	0	-10000	0	-10000	0	0
EPO	-0.002	0.048	-10000	0	-0.25	9	9
VAV1	-0.032	0.13	-10000	0	-0.4	29	29
GRB10	-0.075	0.19	0.18	7	-0.41	58	65
PTPN11	0.016	0.007	-10000	0	-10000	0	0
SCF/KIT	-0.081	0.19	0.19	8	-0.42	59	67
GO:0007205	0.004	0.01	-10000	0	-10000	0	0
MAP2K1	-0.029	0.11	-10000	0	-0.22	59	59
CBL	0.014	0	-10000	0	-10000	0	0
KIT	-0.23	0.5	-10000	0	-1.2	51	51
MAP2K2	-0.029	0.11	-10000	0	-0.22	59	59
SHC/Grb2/SOS1	-0.059	0.17	-10000	0	-0.38	55	55
STAT5A	-0.11	0.27	-10000	0	-0.6	58	58
GRB2	0.014	0	-10000	0	-10000	0	0
response to radiation	-0.078	0.18	0.18	6	-0.4	58	64
SHC/GRAP2	0.002	0.071	-10000	0	-0.27	17	17
PTPRO	-0.083	0.18	0.18	4	-0.4	59	63
SH2B2	-0.076	0.18	0.18	7	-0.4	58	65
DOK1	0.011	0.031	-10000	0	-0.33	2	2
MATK	-0.092	0.19	-10000	0	-0.41	62	62
CREBBP	0.005	0.049	-10000	0	-10000	0	0
BCL2	-0.059	0.26	-10000	0	-1.4	8	8

×

Syndecan-1-mediated signaling events

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
TGFB1	0.007	0.053	-9999	-0.42	4	4
CCL5	-0.06	0.16	-9999	-0.38	50	50
SDCBP	0.009	0.041	-9999	-0.36	3	3
FGFR/FGF2/Syndecan-1	-0.089	0.16	-9999	-0.29	77	77
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.086	0.16	-9999	-0.36	47	47
Syndecan-1/Syntenin	-0.081	0.16	-9999	-0.37	41	41
MAPK3	-0.063	0.14	-9999	-0.36	33	33
HGF/MET	-0.044	0.12	-9999	-0.29	39	39
TGFB1/TGF beta receptor Type II	0.007	0.053	-9999	-0.42	4	4
BSG	0.014	0	-9999	-10000	0	0
keratinocyte migration	-0.085	0.16	-9999	-0.36	47	47
Syndecan-1/RANTES	-0.11	0.18	-9999	-0.41	54	54
Syndecan-1/CD147	-0.07	0.15	-9999	-0.35	39	39
Syndecan-1/Syntenin/PIP2	-0.078	0.15	-9999	-0.36	41	41
LAMA5	-0.002	0.079	-9999	-0.37	11	11
positive regulation of cell-cell adhesion	-0.077	0.15	-9999	-0.35	41	41
MMP7	-0.05	0.13	-9999	-0.31	51	51
HGF	-0.023	0.11	-9999	-0.32	29	29
Syndecan-1/CASK	-0.086	0.15	-9999	-0.28	77	77
Syndecan-1/HGF/MET	-0.11	0.17	-9999	-0.38	57	57
regulation of cell adhesion	-0.056	0.14	-9999	-0.36	29	29
HPSE	-0.005	0.088	-9999	-0.41	12	12
positive regulation of cell migration	-0.089	0.16	-9999	-0.29	77	77
SDC1	-0.09	0.16	-9999	-0.3	77	77
Syndecan-1/Collagen	-0.089	0.16	-9999	-0.29	77	77
PPIB	0.014	0	-9999	-10000	0	0
MET	-0.041	0.14	-9999	-0.37	38	38
PRKACA	0.014	0	-9999	-10000	0	0
MMP9	-0.062	0.15	-9999	-0.35	56	56
MAPK1	-0.063	0.14	-9999	-0.36	33	33
homophilic cell adhesion	-0.088	0.16	-9999	-0.29	77	77
MMP1	-0.097	0.16	-9999	-0.32	88	88

×

IL12-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
IL12/IL12R/TYK2/JAK2/SOCS1	-0.076	0.17	-10000	0	-0.36	52	52
TBX21	-0.28	0.6	-10000	0	-1.3	56	56
B2M	0.008	0.047	-10000	0	-0.42	3	3
TYK2	0.009	0.024	-10000	0	-10000	0	0
IL12RB1	-0.044	0.15	-10000	0	-0.43	35	35
GADD45B	-0.19	0.46	-10000	0	-1.1	49	49
IL12RB2	-0.07	0.17	-10000	0	-0.4	52	52
GADD45G	-0.22	0.52	-10000	0	-1.1	61	61
natural killer cell activation	-0.001	0.024	-10000	0	-10000	0	0
RELB	0.014	0	-10000	0	-10000	0	0
RELA	0.014	0	-10000	0	-10000	0	0
IL18	-0.026	0.12	-10000	0	-0.38	28	28
IL2RA	-0.035	0.13	-10000	0	-0.39	32	32
IFNG	-0.086	0.17	-10000	0	-0.37	67	67
STAT3 (dimer)	-0.18	0.42	-10000	0	-0.88	61	61
HLA-DRB5	-0.041	0.14	-10000	0	-0.36	40	40
FASLG	-0.31	0.62	-10000	0	-1.3	66	66
NF kappa B2 p52/RelB	-0.3	0.51	-10000	0	-1.1	66	66
CD4	0	0.079	-10000	0	-0.42	9	9
SOCS1	0.001	0.065	-10000	0	-0.32	10	10
EntrezGene:6955	0	0.009	-10000	0	-10000	0	0
CD3D	-0.068	0.16	-10000	0	-0.37	57	57
CD3E	-0.069	0.16	-10000	0	-0.37	57	57
CD3G	-0.076	0.17	-10000	0	-0.37	62	62
IL12Rbeta2/JAK2	-0.047	0.13	-10000	0	-0.28	55	55
CCL3	-0.25	0.55	-10000	0	-1.2	58	58
CCL4	-0.27	0.58	-10000	0	-1.3	58	58
HLA-A	0.003	0.065	-10000	0	-0.42	6	6
IL18/IL18R	-0.031	0.16	-10000	0	-0.33	50	50
NOS2	-0.25	0.55	-10000	0	-1.2	60	60
IL12/IL12R/TYK2/JAK2/SPHK2	-0.073	0.17	-10000	0	-0.35	52	52
IL1R1	-0.26	0.55	-10000	0	-1.2	57	57
IL4	0.001	0.029	-10000	0	-0.26	1	1
JAK2	0	0.067	-10000	0	-0.4	6	6
EntrezGene:6957	0	0.009	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.25	0.54	-10000	0	-1.1	66	66
RAB7A	-0.14	0.38	-10000	0	-0.83	49	49
lysosomal transport	-0.13	0.35	-10000	0	-0.77	50	50
FOS	-0.18	0.44	-10000	0	-1.1	43	43
STAT4 (dimer)	-0.21	0.49	-10000	0	-1	61	61
STAT5A (dimer)	-0.34	0.52	-10000	0	-1	76	76
GZMA	-0.28	0.6	-10000	0	-1.4	54	54
GZMB	-0.28	0.59	-10000	0	-1.3	57	57
HLX	0.012	0.027	-10000	0	-0.42	1	1
LCK	-0.31	0.66	-10000	0	-1.3	67	67
TCR/CD3/MHC II/CD4	-0.17	0.42	-10000	0	-0.87	55	55
IL2/IL2R	-0.055	0.18	-10000	0	-0.38	50	50
MAPK14	-0.2	0.49	-10000	0	-1	58	58
CCR5	-0.23	0.54	-10000	0	-1.2	54	54
IL1B	-0.049	0.14	-10000	0	-0.36	43	43
STAT6	-0.036	0.13	0.2	2	-0.25	45	47
STAT4	-0.031	0.12	-10000	0	-0.35	33	33
STAT3	0.014	0	-10000	0	-10000	0	0
STAT1	0.01	0.037	-10000	0	-0.42	2	2
NFKB1	0.014	0	-10000	0	-10000	0	0
NFKB2	0.014	0	-10000	0	-10000	0	0
IL12B	0.001	0.056	-10000	0	-0.26	9	9
CD8A	-0.087	0.17	-10000	0	-0.37	69	69
CD8B	-0.095	0.18	-10000	0	-0.38	73	73
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.075	0.17	0.36	52	-10000	0	52
IL2RB	-0.031	0.13	-10000	0	-0.37	31	31
proteasomal ubiquitin-dependent protein catabolic process	-0.18	0.43	-10000	0	-0.89	61	61
IL2RG	-0.052	0.15	-10000	0	-0.38	44	44
IL12	-0.015	0.1	-10000	0	-0.26	32	32
STAT5A	0.01	0.037	-10000	0	-0.42	2	2
CD247	-0.051	0.15	-10000	0	-0.36	46	46
IL2	0	0.031	-10000	0	-0.25	4	4
SPHK2	0.01	0.037	-10000	0	-0.42	2	2
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.029	0.12	-10000	0	-0.37	27	27
IL12/IL12R/TYK2/JAK2	-0.36	0.82	-10000	0	-1.5	66	66
MAP2K3	-0.2	0.5	-10000	0	-1	60	60
RIPK2	0.014	0	-10000	0	-10000	0	0
MAP2K6	-0.21	0.51	-10000	0	-1	62	62
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.03	0.13	-10000	0	-0.39	29	29
IL18RAP	-0.031	0.12	-10000	0	-0.33	35	35
IL12Rbeta1/TYK2	-0.023	0.12	-10000	0	-0.32	35	35
EOMES	-0.093	0.33	-10000	0	-1.3	19	19
STAT1 (dimer)	-0.23	0.44	-10000	0	-0.86	73	73
T cell proliferation	-0.12	0.34	-10000	0	-0.69	60	60
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.027	0.12	-10000	0	-0.37	29	29
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	-0.75	60	60
ATF2	-0.17	0.44	-10000	0	-0.91	58	58

×

BCR signaling pathway

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
JUN	-0.092	0.18	-10000	0	-0.43	47	47
IKBKB	-0.037	0.093	-10000	0	-0.25	29	29
AKT1	-0.069	0.1	0.18	1	-0.23	61	62
IKBKG	-0.038	0.099	-10000	0	-0.27	29	29
CALM1	-0.092	0.21	-10000	0	-0.56	37	37
PIK3CA	0.008	0.048	-10000	0	-0.38	4	4
MAP3K1	-0.15	0.26	-10000	0	-0.56	61	61
MAP3K7	0.012	0.027	-10000	0	-0.42	1	1
mol:Ca2+	-0.1	0.23	-10000	0	-0.6	37	37
DOK1	0.011	0.031	-10000	0	-0.33	2	2
AP-1	-0.041	0.1	-10000	0	-0.26	36	36
LYN	0.009	0.046	-10000	0	-0.42	3	3
BLNK	-0.041	0.14	-10000	0	-0.39	36	36
SHC1	0.014	0	-10000	0	-10000	0	0
BCR complex	-0.12	0.19	-10000	0	-0.32	109	109
CD22	-0.15	0.26	-10000	0	-0.56	56	56
CAMK2G	-0.08	0.19	-10000	0	-0.52	36	36
CSNK2A1	0.014	0	-10000	0	-10000	0	0
INPP5D	-0.011	0.097	-10000	0	-0.39	16	16
SHC/GRB2/SOS1	-0.11	0.17	-10000	0	-0.46	40	40
GO:0007205	-0.1	0.23	-10000	0	-0.62	37	37
SYK	-0.009	0.093	-10000	0	-0.38	15	15
ELK1	-0.094	0.22	-10000	0	-0.57	37	37
NFATC1	-0.13	0.21	-10000	0	-0.46	61	61
B-cell antigen/BCR complex	-0.12	0.19	-10000	0	-0.32	109	109
PAG1/CSK	0.009	0.059	-10000	0	-0.29	10	10
NFKBIB	-0.003	0.032	-10000	0	-0.076	14	14
HRAS	-0.089	0.2	-10000	0	-0.52	38	38
NFKBIA	-0.003	0.031	-10000	0	-0.075	11	11
NF-kappa-B/RelA/I kappa B beta	0.003	0.026	-10000	0	-10000	0	0
RasGAP/Csk	-0.077	0.15	-10000	0	-0.26	94	94
mol:GDP	-0.099	0.22	-10000	0	-0.58	37	37
PTEN	0.007	0.053	-10000	0	-0.42	4	4
CD79B	-0.059	0.15	-10000	0	-0.33	56	56
NF-kappa-B/RelA/I kappa B alpha	0.003	0.025	-10000	0	-10000	0	0
GRB2	0.014	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.15	0.24	-10000	0	-0.51	69	69
PIK3R1	0.01	0.037	-10000	0	-0.42	2	2
mol:IP3	-0.11	0.24	-10000	0	-0.62	37	37
CSK	0.014	0	-10000	0	-10000	0	0
FOS	-0.085	0.2	-10000	0	-0.52	37	37
CHUK	-0.04	0.1	-10000	0	-0.27	30	30
IBTK	0.004	0.064	-10000	0	-0.42	6	6
CARD11/BCL10/MALT1/TAK1	-0.095	0.21	-10000	0	-0.49	47	47
PTPN6	-0.15	0.26	-10000	0	-0.58	56	56
RELA	0.014	0	-10000	0	-10000	0	0
BCL2A1	-0.001	0.028	-10000	0	-0.086	8	8
VAV2	-0.19	0.28	-10000	0	-0.59	68	68
ubiquitin-dependent protein catabolic process	0	0.031	-10000	0	-0.073	7	7
BTK	-0.045	0.23	0.28	8	-1	14	22
CD19	-0.18	0.26	-10000	0	-0.47	91	91
MAP4K1	-0.021	0.11	-10000	0	-0.37	24	24
CD72	-0.016	0.1	-10000	0	-0.35	22	22
PAG1	-0.003	0.082	-10000	0	-0.42	10	10
MAPK14	-0.12	0.21	-10000	0	-0.46	61	61
SH3BP5	0.009	0.041	-10000	0	-0.36	3	3
PIK3AP1	-0.11	0.27	-10000	0	-0.65	41	41
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.15	0.34	-10000	0	-0.6	68	68
RAF1	-0.079	0.19	-10000	0	-0.49	37	37
RasGAP/p62DOK/SHIP	-0.083	0.17	-10000	0	-0.28	95	95
CD79A	-0.12	0.18	-10000	0	-0.35	102	102
re-entry into mitotic cell cycle	-0.041	0.1	-10000	0	-0.26	36	36
RASA1	0.01	0.037	-10000	0	-0.42	2	2
MAPK3	-0.055	0.15	-10000	0	-0.41	35	35
MAPK1	-0.055	0.15	-10000	0	-0.41	35	35
CD72/SHP1	-0.14	0.26	-10000	0	-0.56	59	59
NFKB1	0.014	0	-10000	0	-10000	0	0
MAPK8	-0.12	0.22	-10000	0	-0.46	62	62
actin cytoskeleton organization	-0.16	0.23	-10000	0	-0.51	64	64
NF-kappa-B/RelA	0.01	0.05	-10000	0	-10000	0	0
Calcineurin	-0.065	0.18	-10000	0	-0.46	36	36
PI3K	-0.16	0.2	-10000	0	-0.44	76	76
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.12	0.27	-10000	0	-0.7	37	37
SOS1	0.014	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.18	0.36	-10000	0	-0.92	45	45
DAPP1	-0.2	0.42	-10000	0	-1.1	43	43
cytokine secretion	-0.12	0.2	-10000	0	-0.43	61	61
mol:DAG	-0.11	0.24	-10000	0	-0.62	37	37
PLCG2	-0.004	0.083	-10000	0	-0.38	12	12
MAP2K1	-0.067	0.17	-10000	0	-0.45	36	36
B-cell antigen/BCR complex/FcgammaRIIB	-0.1	0.17	-10000	0	-0.32	93	93
mol:PI-3-4-5-P3	-0.12	0.14	0.23	1	-0.3	76	77
ETS1	-0.068	0.17	-10000	0	-0.47	35	35
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.1	0.21	-10000	0	-0.34	94	94
B-cell antigen/BCR complex/LYN	-0.14	0.26	-10000	0	-0.5	66	66
MALT1	0.01	0.037	-10000	0	-0.42	2	2
TRAF6	0.014	0	-10000	0	-10000	0	0
RAC1	-0.17	0.26	-10000	0	-0.55	64	64
B-cell antigen/BCR complex/LYN/SYK	-0.14	0.27	-10000	0	-0.59	54	54
CARD11	-0.12	0.26	-10000	0	-0.56	52	52
FCGR2B	-0.007	0.085	-10000	0	-0.33	16	16
PPP3CA	0.012	0.027	-10000	0	-0.42	1	1
BCL10	0.013	0.016	-10000	0	-0.25	1	1
IKK complex	-0.01	0.039	-10000	0	-0.091	26	26
PTPRC	-0.052	0.15	-10000	0	-0.36	46	46
PDPK1	-0.069	0.1	0.17	1	-0.21	68	69
PPP3CB	0.014	0	-10000	0	-10000	0	0
PPP3CC	0.014	0	-10000	0	-10000	0	0
POU2F2	0.002	0.028	-10000	0	-0.089	11	11

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.13	0.34	-10000	0	-0.77	55	55
NCK1/PAK1/Dok-R	-0.091	0.16	-10000	0	-0.39	54	54
NCK1/Dok-R	-0.16	0.4	-10000	0	-0.95	53	53
PIK3CA	0.008	0.048	-10000	0	-0.38	4	4
mol:beta2-estradiol	0.046	0.092	0.22	53	-10000	0	53
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	0.046	0.097	0.23	53	-0.26	2	55
TNIP2	0.014	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.14	0.38	-10000	0	-0.88	53	53
FN1	-0.014	0.1	-10000	0	-0.4	18	18
PLD2	-0.17	0.4	-10000	0	-0.97	53	53
PTPN11	0.014	0	-10000	0	-10000	0	0
GRB14	-0.063	0.15	-10000	0	-0.34	57	57
ELK1	-0.15	0.37	-10000	0	-0.88	53	53
GRB7	-0.013	0.077	-10000	0	-0.26	24	24
PAK1	0.012	0.023	-10000	0	-0.25	2	2
Tie2/Ang1/alpha5/beta1 Integrin	-0.17	0.4	-10000	0	-0.93	54	54
CDKN1A	-0.082	0.25	-10000	0	-0.55	42	42
ITGA5	0.004	0.058	-10000	0	-0.31	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.17	0.4	-10000	0	-0.95	53	53
CRK	0.014	0	-10000	0	-10000	0	0
mol:NO	-0.093	0.27	-10000	0	-0.58	58	58
PLG	-0.18	0.4	-10000	0	-0.97	53	53
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.13	0.33	-10000	0	-0.77	53	53
GRB2	0.014	0	-10000	0	-10000	0	0
PIK3R1	0.01	0.038	-10000	0	-0.42	2	2
ANGPT2	-0.091	0.24	-10000	0	-0.56	33	33
BMX	-0.2	0.4	-10000	0	-0.98	53	53
ANGPT1	-0.24	0.48	-10000	0	-1.2	53	53
tube development	-0.09	0.26	-10000	0	-0.55	57	57
ANGPT4	0.003	0.028	-10000	0	-0.25	3	3
response to hypoxia	-0.013	0.027	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.21	0.42	-10000	0	-1	53	53
alpha5/beta1 Integrin	0.013	0.044	-10000	0	-0.23	8	8
FGF2	-0.078	0.17	-10000	0	-0.4	59	59
STAT5A (dimer)	-0.1	0.3	-10000	0	-0.62	59	59
mol:L-citrulline	-0.093	0.27	-10000	0	-0.58	58	58
AGTR1	-0.042	0.13	-10000	0	-0.35	40	40
MAPK14	-0.16	0.39	-10000	0	-0.92	53	53
Tie2/SHP2	-0.024	0.13	-10000	0	-1.3	1	1
TEK	-0.033	0.14	-10000	0	-1.5	1	1
RPS6KB1	-0.12	0.33	-10000	0	-0.75	54	54
Angiotensin II/AT1	-0.028	0.094	-10000	0	-0.24	40	40
Tie2/Ang1/GRB2	-0.18	0.42	-10000	0	-0.99	53	53
MAPK3	-0.15	0.38	-10000	0	-0.9	53	53
MAPK1	-0.15	0.38	-10000	0	-0.9	53	53
Tie2/Ang1/GRB7	-0.19	0.42	-10000	0	-1	53	53
NFKB1	0.014	0	-10000	0	-10000	0	0
MAPK8	-0.17	0.4	-10000	0	-0.97	53	53
PI3K	-0.15	0.38	-10000	0	-0.88	53	53
FES	-0.17	0.39	-10000	0	-0.92	54	54
Crk/Dok-R	-0.16	0.4	-10000	0	-0.95	53	53
Tie2/Ang1/ABIN2	-0.18	0.42	-10000	0	-0.99	53	53
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.12	0.31	-10000	0	-0.69	57	57
STAT5A	0.01	0.037	-10000	0	-0.42	2	2
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.12	0.33	-10000	0	-0.76	53	53
Tie2/Ang2	-0.13	0.33	-10000	0	-0.71	57	57
Tie2/Ang1	-0.19	0.43	-10000	0	-1	53	53
FOXO1	-0.12	0.32	-10000	0	-0.7	57	57
ELF1	0.011	0.03	-10000	0	-0.41	1	1
ELF2	-0.17	0.4	-10000	0	-0.95	53	53
mol:Choline	-0.16	0.39	-10000	0	-0.93	53	53
cell migration	-0.054	0.089	-10000	0	-0.22	55	55
FYN	-0.1	0.29	-10000	0	-0.61	57	57
DOK2	-0.004	0.086	-10000	0	-0.42	11	11
negative regulation of cell cycle	-0.073	0.23	-10000	0	-0.47	59	59
ETS1	-0.033	0.094	-10000	0	-0.22	46	46
PXN	-0.097	0.28	-10000	0	-0.63	54	54
ITGB1	0.013	0.016	-10000	0	-0.25	1	1
NOS3	-0.11	0.3	-10000	0	-0.66	56	56
RAC1	0.014	0	-10000	0	-10000	0	0
TNF	-0.07	0.15	-10000	0	-0.29	73	73
MAPKKK cascade	-0.16	0.39	-10000	0	-0.93	53	53
RASA1	0.01	0.037	-10000	0	-0.42	2	2
Tie2/Ang1/Shc	-0.18	0.42	-10000	0	-0.99	53	53
NCK1	0.014	0	-10000	0	-10000	0	0
vasculogenesis	-0.081	0.24	-10000	0	-0.52	58	58
mol:Phosphatidic acid	-0.16	0.39	-10000	0	-0.93	53	53
mol:Angiotensin II	0	0.005	-10000	0	-10000	0	0
mol:NADP	-0.093	0.27	-10000	0	-0.58	58	58
Rac1/GTP	-0.16	0.28	-10000	0	-0.7	54	54
MMP2	-0.19	0.41	-10000	0	-0.99	53	53

×

Glypican 1 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
GPC1/FGF2 dimer/FGFR1 dimer	-0.064	0.13	-10000	0	-0.26	75	75
fibroblast growth factor receptor signaling pathway	-0.064	0.13	-10000	0	-0.26	75	75
LAMA1	-0.08	0.17	-10000	0	-0.36	67	67
PRNP	0.009	0.041	-10000	0	-0.36	3	3
GPC1/SLIT2	-0.036	0.11	-10000	0	-0.3	31	31
SMAD2	0.002	0.066	-10000	0	-0.21	20	20
GPC1/PrPc/Cu2+	-0.011	0.078	-10000	0	-0.2	36	36
GPC1/Laminin alpha1	-0.076	0.15	-10000	0	-0.27	89	89
TDGF1	-0.001	0.041	-10000	0	-0.25	7	7
CRIPTO/GPC1	-0.022	0.091	-10000	0	-0.29	20	20
APP/GPC1	-0.025	0.11	-10000	0	-0.27	42	42
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.016	0.08	-10000	0	-0.24	24	24
FLT1	0.011	0.031	-10000	0	-0.33	2	2
GPC1/TGFB/TGFBR1/TGFBR2	0	0.076	-10000	0	-0.24	20	20
SERPINC1	0.007	0.028	-10000	0	-0.25	3	3
FYN	-0.012	0.075	-10000	0	-0.24	20	20
FGR	-0.025	0.088	-10000	0	-0.24	31	31
positive regulation of MAPKKK cascade	-0.067	0.15	-10000	0	-0.34	47	47
SLIT2	-0.02	0.1	-10000	0	-0.31	28	28
GPC1/NRG	-0.048	0.12	-10000	0	-0.22	73	73
NRG1	-0.038	0.12	-10000	0	-0.3	43	43
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.007	0.085	-10000	0	-0.25	23	23
LYN	-0.015	0.082	-10000	0	-0.25	22	22
mol:Spermine	-0.023	0.087	-10000	0	-0.24	34	34
cell growth	-0.064	0.13	-10000	0	-0.26	75	75
BMP signaling pathway	0.033	0.12	0.35	34	-10000	0	34
SRC	-0.013	0.077	-10000	0	-0.24	21	21
TGFBR1	0.014	0	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.13	0.18	-10000	0	-0.33	108	108
GPC1	-0.033	0.12	-10000	0	-0.35	34	34
TGFBR1 (dimer)	0.014	0	-10000	0	-10000	0	0
VEGFA	0.004	0.052	-10000	0	-0.27	9	9
BLK	-0.066	0.12	-10000	0	-0.26	60	60
HCK	-0.026	0.094	-10000	0	-0.25	34	34
FGF2	-0.079	0.18	-10000	0	-0.4	59	59
FGFR1	-0.002	0.07	-10000	0	-0.3	13	13
VEGFR1 homodimer	0.011	0.031	-10000	0	-0.33	2	2
TGFBR2	0.013	0.016	-10000	0	-0.25	1	1
cell death	-0.025	0.11	-10000	0	-0.27	42	42
ATIII/GPC1	-0.017	0.089	-10000	0	-0.23	37	37
PLA2G2A/GPC1	-0.11	0.14	-10000	0	-0.24	133	133
LCK	-0.059	0.12	-10000	0	-0.25	64	64
neuron differentiation	-0.047	0.12	-10000	0	-0.22	73	73
PrPc/Cu2+	0.007	0.028	-10000	0	-0.25	3	3
APP	-0.006	0.09	-10000	0	-0.42	12	12
TGFBR2 (dimer)	0.013	0.016	-10000	0	-0.25	1	1

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.064	0.14	-9999	-0.26	75	75
FZD6	-0.017	0.11	-9999	-0.42	19	19
WNT6	-0.018	0.097	-9999	-0.3	26	26
WNT4	-0.06	0.15	-9999	-0.35	54	54
FZD3	0.012	0.027	-9999	-0.42	1	1
WNT5A	-0.03	0.12	-9999	-0.32	35	35
WNT11	-0.025	0.11	-9999	-0.33	30	30

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	-0.029	0.12	-10000	0	-0.38	23	23
NFATC2	-0.11	0.28	-10000	0	-0.65	43	43
NFATC3	-0.011	0.07	-10000	0	-0.22	11	11
CD40LG	-0.24	0.4	-10000	0	-0.84	66	66
ITCH	-0.025	0.086	-10000	0	-10000	0	0
CBLB	-0.026	0.086	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.25	0.49	-10000	0	-1.1	61	61
JUNB	0.012	0.023	-10000	0	-0.25	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.041	0.1	-10000	0	-0.25	37	37
T cell anergy	-0.076	0.14	-10000	0	-0.37	39	39
TLE4	-0.076	0.23	-10000	0	-0.64	27	27
Jun/NFAT1-c-4/p21SNFT	-0.17	0.38	-10000	0	-0.83	51	51
AP-1/NFAT1-c-4	-0.23	0.45	-10000	0	-0.93	62	62
IKZF1	-0.097	0.27	-10000	0	-0.66	40	40
T-helper 2 cell differentiation	-0.15	0.34	-10000	0	-0.81	47	47
AP-1/NFAT1	-0.07	0.2	-10000	0	-0.46	40	40
CALM1	-0.019	0.06	-10000	0	-10000	0	0
EGR2	-0.13	0.35	-10000	0	-0.92	27	27
EGR3	-0.16	0.41	-10000	0	-1	36	36
NFAT1/FOXP3	-0.1	0.26	-10000	0	-0.53	56	56
EGR1	0.001	0.061	-10000	0	-0.28	11	11
JUN	0.001	0.026	-10000	0	-0.26	1	1
EGR4	-0.013	0.075	-10000	0	-0.25	24	24
mol:Ca2+	-0.033	0.061	-10000	0	-0.16	37	37
GBP3	-0.094	0.27	-10000	0	-0.66	40	40
FOSL1	-0.051	0.14	-10000	0	-0.35	47	47
NFAT1-c-4/MAF/IRF4	-0.16	0.35	-10000	0	-0.8	50	50
DGKA	-0.069	0.23	-10000	0	-0.54	35	35
CREM	0.013	0.016	-10000	0	-0.25	1	1
NFAT1-c-4/PPARG	-0.15	0.36	-10000	0	-0.85	44	44
CTLA4	-0.12	0.28	-10000	0	-0.62	51	51
NFAT1-c-4 (dimer)/EGR1	-0.16	0.36	-10000	0	-0.84	46	46
NFAT1-c-4 (dimer)/EGR4	-0.16	0.36	-10000	0	-0.84	47	47
FOS	-0.006	0.051	-10000	0	-0.27	8	8
IFNG	-0.33	0.55	-10000	0	-1.1	80	80
T cell activation	-0.082	0.22	-10000	0	-0.66	17	17
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	0.11	0.28	0.78	29	-10000	0	29
TNF	-0.17	0.35	-10000	0	-0.82	48	48
FASLG	-0.34	0.66	-10000	0	-1.5	63	63
TBX21	-0.075	0.16	-10000	0	-0.38	52	52
BATF3	0.002	0.068	-10000	0	-0.38	8	8
PRKCQ	-0.069	0.17	-10000	0	-0.41	50	50
PTPN1	-0.063	0.21	-10000	0	-0.52	33	33
NFAT1-c-4/ICER1	-0.15	0.36	-10000	0	-0.84	44	44
GATA3	-0.056	0.15	-10000	0	-0.38	47	47
T-helper 1 cell differentiation	-0.32	0.53	-10000	0	-1.1	80	80
IL2RA	-0.22	0.44	-10000	0	-0.97	57	57
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.063	0.21	-10000	0	-0.52	33	33
E2F1	0.015	0.038	-10000	0	-0.42	2	2
PPARG	0.007	0.051	-10000	0	-0.35	5	5
SLC3A2	-0.063	0.21	-10000	0	-0.52	33	33
IRF4	-0.043	0.15	-10000	0	-0.42	35	35
PTGS2	-0.23	0.4	-10000	0	-0.84	64	64
CSF2	-0.21	0.38	-10000	0	-0.82	61	61
JunB/Fra1/NFAT1-c-4	-0.17	0.36	-10000	0	-0.85	44	44
IL4	-0.16	0.36	-10000	0	-0.86	46	46
IL5	-0.22	0.38	-10000	0	-0.81	62	62
IL2	-0.083	0.23	-10000	0	-0.68	16	16
IL3	-0.044	0.055	-10000	0	-10000	0	0
RNF128	-0.1	0.19	-10000	0	-0.5	37	37
NFATC1	-0.11	0.29	-10000	0	-0.78	29	29
CDK4	0.083	0.19	0.52	24	-10000	0	24
PTPRK	-0.07	0.22	-10000	0	-0.56	34	34
IL8	-0.22	0.39	-10000	0	-0.84	63	63
POU2F1	0.014	0.002	-10000	0	-10000	0	0

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.093	0.19	-9999	-0.39	77	77
KLHL20	-0.019	0.082	-9999	-0.21	13	13
CYFIP2	-0.009	0.094	-9999	-0.39	15	15
Rac1/GDP	-0.034	0.12	-9999	-0.22	73	73
ENAH	-0.097	0.19	-9999	-0.39	77	77
AP1M1	0.014	0	-9999	-10000	0	0
RAP1B	0.013	0.016	-9999	-0.25	1	1
RAP1A	0.014	0	-9999	-10000	0	0
CTNNB1	0.014	0	-9999	-10000	0	0
CDC42/GTP	-0.043	0.063	-9999	-0.27	1	1
ABI1/Sra1/Nap1	-0.034	0.046	-9999	-0.15	17	17
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.057	0.13	-9999	-0.23	86	86
RAPGEF1	-0.072	0.17	-9999	-0.33	77	77
CTNND1	0.014	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.1	0.19	-9999	-0.4	77	77
CRK	-0.083	0.18	-9999	-0.36	77	77
E-cadherin/gamma catenin/alpha catenin	-0.061	0.12	-9999	-0.24	77	77
alphaE/beta7 Integrin	0.001	0.074	-9999	-0.28	17	17
IQGAP1	0.014	0	-9999	-10000	0	0
NCKAP1	0.014	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.024	0.024	-9999	-0.21	2	2
DLG1	-0.092	0.19	-9999	-0.39	77	77
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.033	0.048	-9999	-0.18	3	3
MLLT4	0.009	0.041	-9999	-0.36	3	3
ARF6/GTP/NME1/Tiam1	0.011	0.059	-9999	-0.21	17	17
PI3K	-0.041	0.06	-9999	-0.23	3	3
ARF6	0.014	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.084	0.14	-9999	-0.27	96	96
TIAM1	-0.015	0.11	-9999	-0.41	18	18
E-cadherin(dimer)/Ca2+	-0.04	0.1	-9999	-0.19	77	77
AKT1	-0.024	0.036	-9999	-0.14	2	2
PIK3R1	0.01	0.037	-9999	-0.42	2	2
CDH1	-0.13	0.2	-9999	-0.39	92	92
RhoA/GDP	-0.035	0.12	-9999	-0.22	73	73
actin cytoskeleton organization	-0.013	0.063	-9999	-0.15	13	13
CDC42/GDP	-0.035	0.12	-9999	-0.22	73	73
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.051	0.11	-9999	-0.21	77	77
ITGB7	-0.013	0.1	-9999	-0.41	17	17
RAC1	0.014	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.043	0.11	-9999	-0.21	77	77
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.047	0.1	-9999	-0.2	77	77
mol:GDP	-0.048	0.13	-9999	-0.25	77	77
CDC42/GTP/IQGAP1	0.019	0	-9999	-10000	0	0
JUP	0.005	0.051	-9999	-0.3	7	7
p120 catenin/RhoA/GDP	-0.035	0.12	-9999	-0.22	73	73
RAC1/GTP/IQGAP1	0.019	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	-0.007	0.048	-9999	-0.12	15	15
NME1	0.014	0	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	-0.096	0.19	-9999	-0.39	77	77
regulation of cell-cell adhesion	-0.038	0.056	-9999	-0.24	1	1
WASF2	-0.017	0.025	-9999	-0.1	3	3
Rap1/GTP	-0.022	0.091	-9999	-0.31	1	1
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.051	0.12	-9999	-0.21	86	86
CCND1	-0.01	0.058	-9999	-0.16	14	14
VAV2	-0.094	0.2	-9999	-0.39	82	82
RAP1/GDP	-0.027	0.1	-9999	-0.28	2	2
adherens junction assembly	-0.093	0.18	-9999	-0.38	77	77
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	-0.044	0.12	-9999	-0.36	11	11
E-cadherin/beta catenin	-0.084	0.14	-9999	-0.31	77	77
mol:GTP	0	0	-9999	-10000	0	0
SRC	-0.093	0.19	-9999	-0.39	77	77
PIK3CA	0.008	0.048	-9999	-0.38	4	4
Rac1/GTP	-0.069	0.099	-9999	-0.31	16	16
E-cadherin/beta catenin/alpha catenin	-0.057	0.12	-9999	-0.24	77	77
ITGAE	0.014	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.1	0.2	-9999	-0.41	77	77

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.026	0.12	-9999	-0.26	41	41
NF kappa B1 p50/RelA/I kappa B alpha	-0.022	0.1	-9999	-0.26	18	18
AP1	-0.078	0.11	-9999	-0.33	24	24
mol:PIP3	-0.081	0.1	-9999	-0.33	25	25
AKT1	0.006	0.088	-9999	-0.36	7	7
PTK2B	-0.026	0.095	-9999	-0.29	21	21
RHOA	0.006	0.045	-9999	-0.26	2	2
PIK3CB	0.014	0.001	-9999	-10000	0	0
mol:Ca2+	-0.027	0.086	-9999	-0.2	40	40
MAGI3	0.01	0.037	-9999	-0.42	2	2
RELA	0.014	0	-9999	-10000	0	0
apoptosis	-0.07	0.13	-9999	-0.26	67	67
HRAS/GDP	0.01	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	-0.038	0.1	-9999	-0.25	33	33
NF kappa B1 p50/RelA	-0.066	0.11	-9999	-0.31	26	26
endothelial cell migration	-0.052	0.16	-9999	-0.36	45	45
ADCY4	-0.068	0.14	-9999	-0.33	45	45
ADCY5	-0.091	0.17	-9999	-0.37	56	56
ADCY6	-0.069	0.15	-9999	-0.33	48	48
ADCY7	-0.068	0.15	-9999	-0.35	44	44
ADCY1	-0.097	0.17	-9999	-0.35	64	64
ADCY2	-0.12	0.18	-9999	-0.38	73	73
ADCY3	-0.067	0.15	-9999	-0.34	44	44
ADCY8	-0.072	0.14	-9999	-0.34	45	45
ADCY9	-0.068	0.15	-9999	-0.34	45	45
GSK3B	-0.02	0.091	-9999	-0.27	20	20
arachidonic acid secretion	-0.067	0.14	-9999	-0.33	42	42
GNG2	-0.003	0.082	-9999	-0.42	10	10
TRIP6	0.008	0.057	-9999	-0.28	9	9
GNAO1	-0.079	0.14	-9999	-0.26	81	81
HRAS	0.014	0	-9999	-10000	0	0
NFKBIA	-0.037	0.11	-9999	-0.25	41	41
GAB1	0.01	0.037	-9999	-0.42	2	2
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.032	0.22	-9999	-0.88	17	17
JUN	0.013	0.016	-9999	-0.25	1	1
LPA/LPA2/NHERF2	0.009	0.04	-9999	-0.21	6	6
TIAM1	-0.061	0.25	-9999	-1	17	17
PIK3R1	0.01	0.037	-9999	-0.42	2	2
mol:IP3	-0.027	0.088	-9999	-0.21	40	40
PLCB3	0.013	0.035	-9999	-0.22	4	4
FOS	0.006	0.045	-9999	-0.25	8	8
positive regulation of mitosis	-0.067	0.14	-9999	-0.33	42	42
LPA/LPA1-2-3	-0.075	0.14	-9999	-0.26	69	69
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.01	0.037	-9999	-0.42	2	2
stress fiber formation	-0.037	0.1	-9999	-0.31	22	22
GNAZ	-0.056	0.13	-9999	-0.28	57	57
EGFR/PI3K-beta/Gab1	-0.083	0.11	-9999	-0.34	25	25
positive regulation of dendritic cell cytokine production	-0.075	0.13	-9999	-0.26	69	69
LPA/LPA2/MAGI-3	0.009	0.042	-9999	-0.24	5	5
ARHGEF1	-0.015	0.094	-9999	-0.22	35	35
GNAI2	-0.031	0.11	-9999	-0.28	35	35
GNAI3	-0.031	0.11	-9999	-0.28	35	35
GNAI1	-0.034	0.11	-9999	-0.28	37	37
LPA/LPA3	-0.066	0.11	-9999	-0.22	83	83
LPA/LPA2	0.001	0.042	-9999	-0.27	4	4
LPA/LPA1	-0.046	0.13	-9999	-0.27	54	54
HB-EGF/EGFR	-0.041	0.11	-9999	-0.25	45	45
HBEGF	-0.036	0.11	-9999	-0.23	59	59
mol:DAG	-0.027	0.088	-9999	-0.21	40	40
cAMP biosynthetic process	-0.089	0.16	-9999	-0.3	74	74
NFKB1	0.014	0	-9999	-10000	0	0
SRC	0.012	0.027	-9999	-0.42	1	1
GNB1	0.014	0.001	-9999	-10000	0	0
LYN	-0.041	0.12	-9999	-0.33	20	20
GNAQ	-0.037	0.088	-9999	-0.23	38	38
LPAR2	0.008	0.048	-9999	-0.38	4	4
LPAR3	-0.091	0.16	-9999	-0.32	83	83
LPAR1	-0.056	0.15	-9999	-0.36	45	45
IL8	-0.079	0.16	-9999	-0.4	41	41
PTK2	-0.068	0.12	-9999	-0.24	65	65
Rac1/GDP	0.01	0	-9999	-10000	0	0
CASP3	-0.071	0.13	-9999	-0.26	67	67
EGFR	-0.021	0.1	-9999	-0.29	30	30
PLCG1	-0.041	0.1	-9999	-0.25	40	40
PLD2	-0.068	0.12	-9999	-0.24	68	68
G12/G13	-0.017	0.1	-9999	-0.25	35	35
PI3K-beta	-0.035	0.081	-9999	-0.34	11	11
cell migration	-0.022	0.085	-9999	-0.25	22	22
SLC9A3R2	0.011	0.031	-9999	-0.33	2	2
PXN	-0.038	0.11	-9999	-0.31	22	22
HRAS/GTP	-0.069	0.14	-9999	-0.34	42	42
RAC1	0.014	0	-9999	-10000	0	0
MMP9	-0.062	0.15	-9999	-0.35	56	56
PRKCE	0.013	0.016	-9999	-0.25	1	1
PRKCD	-0.022	0.084	-9999	-0.24	13	13
Gi(beta/gamma)	-0.066	0.14	-9999	-0.33	43	43
mol:LPA	-0.008	0.037	-9999	-0.16	9	9
TRIP6/p130 Cas/FAK1/Paxillin	-0.047	0.13	-9999	-0.36	21	21
MAPKKK cascade	-0.067	0.14	-9999	-0.33	42	42
contractile ring contraction involved in cytokinesis	0.006	0.045	-9999	-0.26	2	2
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.054	0.1	-9999	-0.24	49	49
GNA15	-0.046	0.1	-9999	-0.24	46	46
GNA12	0.014	0	-9999	-10000	0	0
GNA13	0.014	0	-9999	-10000	0	0
MAPT	-0.039	0.11	-9999	-0.26	33	33
GNA11	-0.037	0.088	-9999	-0.23	38	38
Rac1/GTP	-0.035	0.23	-9999	-0.93	17	17
MMP2	-0.053	0.16	-9999	-0.37	45	45

×

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	-0.042	0.1	-10000	0	-0.2	77	77
epithelial cell differentiation	-0.042	0.1	-10000	0	-0.19	77	77
CYFIP2	-0.009	0.094	-10000	0	-0.39	15	15
ENAH	-0.015	0.079	-10000	0	-0.22	8	8
EGFR	-0.021	0.1	-10000	0	-0.29	30	30
EPHA2	-0.001	0.073	-10000	0	-0.34	11	11
MYO6	-0.045	0.1	-10000	0	-0.18	84	84
CTNNB1	0.014	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.014	0.057	-10000	0	-0.24	12	12
AQP5	-0.042	0.1	-10000	0	-0.5	4	4
CTNND1	0.014	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.037	0.093	-10000	0	-0.18	77	77
regulation of calcium-dependent cell-cell adhesion	-0.048	0.1	-10000	0	-0.19	81	81
EGF	-0.088	0.17	-10000	0	-0.37	71	71
NCKAP1	0.014	0	-10000	0	-10000	0	0
AQP3	-0.054	0.14	-10000	0	-0.48	18	18
cortical microtubule organization	-0.042	0.1	-10000	0	-0.19	77	77
GO:0000145	-0.037	0.088	-10000	0	-0.17	77	77
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.04	0.1	-10000	0	-0.19	77	77
MLLT4	0.009	0.041	-10000	0	-0.36	3	3
ARF6/GDP	-0.049	0.069	-10000	0	-0.25	5	5
ARF6	0.014	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.027	0.04	-10000	0	-0.21	6	6
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.03	0.09	-10000	0	-0.21	2	2
PVRL2	0.014	0	-10000	0	-10000	0	0
ZYX	-0.038	0.096	-10000	0	-0.18	77	77
ARF6/GTP	0.031	0.037	-10000	0	-0.19	6	6
CDH1	-0.13	0.2	-10000	0	-0.39	92	92
EGFR/EGFR/EGF/EGF	-0.11	0.13	-10000	0	-0.34	43	43
RhoA/GDP	-0.037	0.094	-10000	0	-0.18	77	77
actin cytoskeleton organization	-0.04	0.098	-10000	0	-0.33	3	3
IGF-1R heterotetramer	0.009	0.041	-10000	0	-0.36	3	3
GIT1	0.014	0	-10000	0	-10000	0	0
IGF1R	0.009	0.041	-10000	0	-0.36	3	3
IGF1	-0.023	0.12	-10000	0	-0.38	25	25
DIAPH1	-0.02	0.12	-10000	0	-0.58	12	12
Wnt receptor signaling pathway	0.042	0.1	0.19	77	-10000	0	77
RHOA	0.014	0	-10000	0	-10000	0	0
RhoA/GTP	-0.049	0.069	-10000	0	-0.25	5	5
CTNNA1	0.014	0	-10000	0	-10000	0	0
VCL	-0.041	0.1	-10000	0	-0.33	3	3
EFNA1	0.014	0	-10000	0	-10000	0	0
LPP	-0.035	0.091	-10000	0	-10000	0	0
Ephrin A1/EPHA2	-0.059	0.082	-10000	0	-0.24	9	9
SEC6/SEC8	-0.049	0.068	-10000	0	-10000	0	0
MGAT3	-0.049	0.1	-10000	0	-0.19	81	81
HGF/MET	-0.089	0.11	-10000	0	-0.32	32	32
HGF	-0.023	0.11	-10000	0	-0.32	29	29
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.043	0.1	-10000	0	-0.2	77	77
actin cable formation	-0.003	0.079	-10000	0	-0.24	4	4
KIAA1543	-0.071	0.12	-10000	0	-0.3	27	27
KIFC3	-0.038	0.094	-10000	0	-0.18	78	78
NCK1	0.014	0	-10000	0	-10000	0	0
EXOC3	0.013	0.016	-10000	0	-0.25	1	1
ACTN1	-0.041	0.095	-10000	0	-0.18	81	81
NCK1/GIT1	0.02	0	-10000	0	-10000	0	0
mol:GDP	-0.042	0.1	-10000	0	-0.19	77	77
EXOC4	0.014	0	-10000	0	-10000	0	0
STX4	-0.038	0.094	-10000	0	-0.18	77	77
PIP5K1C	-0.038	0.094	-10000	0	-0.18	77	77
LIMA1	0.014	0	-10000	0	-10000	0	0
ABI1	0.014	0	-10000	0	-10000	0	0
ROCK1	-0.018	0.083	-10000	0	-0.22	5	5
adherens junction assembly	-0.055	0.11	-10000	0	-0.34	14	14
IGF-1R heterotetramer/IGF1	-0.07	0.095	-10000	0	-0.33	12	12
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.017	0.029	-10000	0	-0.24	3	3
MET	-0.041	0.14	-10000	0	-0.37	38	38
PLEKHA7	-0.049	0.1	-10000	0	-0.19	85	85
mol:GTP	0.026	0.04	-10000	0	-0.21	6	6
establishment of epithelial cell apical/basal polarity	-0.017	0.085	-10000	0	-10000	0	0
cortical actin cytoskeleton stabilization	-0.042	0.1	-10000	0	-0.2	77	77
regulation of cell-cell adhesion	-0.04	0.098	-10000	0	-0.33	3	3
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.043	0.1	-10000	0	-0.2	77	77

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	-0.008	0.072	-10000	0	-0.27	6	6
adherens junction organization	-0.044	0.12	-10000	0	-0.22	77	77
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.015	0.085	-10000	0	-0.28	7	7
FMN1	-0.053	0.13	-10000	0	-0.23	77	77
mol:IP3	-0.014	0.07	-10000	0	-0.24	7	7
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.047	0.12	-10000	0	-0.22	77	77
CTNNB1	0.016	0.004	-10000	0	-10000	0	0
AKT1	-0.016	0.081	-10000	0	-0.31	4	4
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.079	0.17	-10000	0	-0.34	77	77
CTNND1	0.013	0.002	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.039	0.11	-10000	0	-0.2	77	77
VASP	-0.04	0.11	-10000	0	-0.21	77	77
ZYX	-0.041	0.11	-10000	0	-0.21	77	77
JUB	-0.041	0.11	-10000	0	-0.21	77	77
EGFR(dimer)	-0.053	0.13	-10000	0	-0.23	78	78
E-cadherin/beta catenin-gamma catenin	-0.058	0.12	-10000	0	-0.23	77	77
mol:PI-3-4-5-P3	-0.021	0.085	-10000	0	-0.25	8	8
PIK3CA	0.008	0.049	-10000	0	-0.38	4	4
PI3K	-0.021	0.087	-10000	0	-0.26	8	8
FYN	-0.004	0.063	-10000	0	-0.25	4	4
mol:Ca2+	-0.013	0.069	-10000	0	-0.23	7	7
JUP	0.008	0.051	-10000	0	-0.29	7	7
PIK3R1	0.01	0.038	-10000	0	-0.43	2	2
mol:DAG	-0.014	0.07	-10000	0	-0.24	7	7
CDH1	-0.13	0.2	-10000	0	-0.39	92	92
RhoA/GDP	-0.015	0.085	-10000	0	-0.28	7	7
establishment of polarity of embryonic epithelium	-0.039	0.11	-10000	0	-0.2	77	77
SRC	0.012	0.027	-10000	0	-0.42	1	1
RAC1	0.014	0	-10000	0	-10000	0	0
RHOA	0.014	0	-10000	0	-10000	0	0
EGFR	-0.021	0.1	-10000	0	-0.29	30	30
CASR	-0.015	0.069	-10000	0	-0.25	6	6
RhoA/GTP	-0.006	0.065	-10000	0	-0.28	3	3
AKT2	-0.016	0.081	-10000	0	-0.31	4	4
actin cable formation	-0.046	0.12	-10000	0	-0.37	13	13
apoptosis	0.016	0.079	0.26	7	-10000	0	7
CTNNA1	0.013	0.002	-10000	0	-10000	0	0
mol:GDP	-0.024	0.088	-10000	0	-0.23	21	21
PIP5K1A	-0.04	0.11	-10000	0	-0.21	77	77
PLCG1	-0.014	0.072	-10000	0	-0.29	4	4
Rac1/GTP	-0.045	0.12	-10000	0	-0.21	78	78
homophilic cell adhesion	0	0.002	-10000	0	-10000	0	0

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.029	0.12	-9999	-0.39	28	28
GNB1/GNG2	-0.052	0.14	-9999	-0.34	32	32
mol:DAG	-0.045	0.13	-9999	-0.32	32	32
PLCG1	-0.047	0.13	-9999	-0.32	32	32
YES1	-0.058	0.13	-9999	-0.24	76	76
FZD3	0.012	0.027	-9999	-0.42	1	1
FZD6	-0.017	0.11	-9999	-0.42	19	19
G protein	-0.045	0.13	-9999	-0.33	32	32
MAP3K7	-0.051	0.12	-9999	-0.31	32	32
mol:Ca2+	-0.044	0.12	-9999	-0.31	32	32
mol:IP3	-0.045	0.13	-9999	-0.32	32	32
NLK	0.005	0.011	-9999	-10000	0	0
GNB1	0.014	0	-9999	-10000	0	0
CAMK2A	-0.059	0.13	-9999	-0.31	39	39
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.064	0.14	-9999	-0.26	75	75
CSNK1A1	0.014	0	-9999	-10000	0	0
GNAS	-0.055	0.13	-9999	-0.32	34	34
GO:0007205	-0.046	0.13	-9999	-0.31	32	32
WNT6	-0.018	0.097	-9999	-0.3	26	26
WNT4	-0.06	0.15	-9999	-0.35	54	54
NFAT1/CK1 alpha	-0.054	0.14	-9999	-0.34	37	37
GNG2	-0.003	0.082	-9999	-0.42	10	10
WNT5A	-0.03	0.12	-9999	-0.32	35	35
WNT11	-0.025	0.11	-9999	-0.33	30	30
CDC42	-0.051	0.13	-9999	-0.33	28	28

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.011	0.053	-10000	0	-0.29	8	8
Necdin/E2F1	-0.008	0.089	-10000	0	-0.29	24	24
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.025	0.1	-10000	0	-0.21	52	52
NGF (dimer)/p75(NTR)/BEX1	-0.075	0.13	-10000	0	-0.27	62	62
NT-4/5 (dimer)/p75(NTR)	-0.042	0.11	-10000	0	-0.22	65	65
IKBKB	0.014	0	-10000	0	-10000	0	0
AKT1	-0.023	0.09	-10000	0	-0.2	42	42
IKBKG	0.014	0	-10000	0	-10000	0	0
BDNF	-0.093	0.17	-10000	0	-0.33	82	82
MGDIs/NGR/p75(NTR)/LINGO1	-0.074	0.16	-10000	0	-0.31	68	68
FURIN	0.014	0	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.086	0.14	-10000	0	-0.28	74	74
LINGO1	-0.037	0.14	-10000	0	-0.41	32	32
Sortilin/TRAF6/NRIF	-0.006	0.03	-10000	0	-10000	0	0
proBDNF (dimer)	-0.093	0.17	-10000	0	-0.33	82	82
NTRK1	-0.01	0.089	-10000	0	-0.32	19	19
RTN4R	-0.036	0.13	-10000	0	-0.38	33	33
neuron apoptosis	-0.059	0.12	-10000	0	-0.35	18	18
IRAK1	0.014	0	-10000	0	-10000	0	0
SHC1	-0.036	0.1	-10000	0	-0.24	39	39
ARHGDIA	0.012	0.027	-10000	0	-0.42	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	-0.03	0.11	-10000	0	-0.23	47	47
MAGEH1	0.009	0.046	-10000	0	-0.42	3	3
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.046	0.13	-10000	0	-0.26	58	58
Mammalian IAPs/DIABLO	-0.01	0.1	-10000	0	-0.24	35	35
proNGF (dimer)	-0.012	0.093	-10000	0	-0.34	19	19
MAGED1	0.012	0.027	-10000	0	-0.42	1	1
APP	-0.006	0.09	-10000	0	-0.42	12	12
NT-4/5 (dimer)	0	0.041	-10000	0	-0.25	7	7
ZNF274	0.014	0	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.022	0.086	-10000	0	-0.2	40	40
NGF	-0.012	0.093	-10000	0	-0.34	19	19
cell cycle arrest	-0.022	0.098	0.14	10	-0.19	45	55
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.011	0.081	-10000	0	-0.2	35	35
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.025	0.09	-10000	0	-0.24	27	27
NCSTN	0.014	0	-10000	0	-10000	0	0
mol:GTP	-0.036	0.1	-10000	0	-0.24	42	42
PSENEN	0.014	0	-10000	0	-10000	0	0
mol:ceramide	-0.033	0.1	-10000	0	-0.23	46	46
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.007	0.081	-10000	0	-0.32	4	4
p75(NTR)/beta APP	-0.046	0.12	-10000	0	-0.23	70	70
BEX1	-0.063	0.14	-10000	0	-0.29	66	66
mol:GDP	-0.044	0.098	-10000	0	-0.25	39	39
NGF (dimer)	-0.021	0.087	-10000	0	-0.22	29	29
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.06	0.15	-10000	0	-0.28	68	68
PIK3R1	0.01	0.037	-10000	0	-0.42	2	2
RAC1/GTP	-0.026	0.086	-10000	0	-0.21	39	39
MYD88	0.012	0.027	-10000	0	-0.42	1	1
CHUK	0.012	0.027	-10000	0	-0.42	1	1
NGF (dimer)/p75(NTR)/PKA	-0.036	0.1	-10000	0	-0.24	42	42
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	-0.29	2	2
NT3 (dimer)	-0.018	0.083	-10000	0	-0.25	29	29
TP53	-0.06	0.11	-10000	0	-0.26	29	29
PRDM4	-0.033	0.099	-10000	0	-0.22	45	45
BDNF (dimer)	-0.11	0.13	-10000	0	-0.25	94	94
PIK3CA	0.008	0.048	-10000	0	-0.38	4	4
SORT1	0.001	0.074	-10000	0	-0.42	8	8
activation of caspase activity	-0.027	0.1	-10000	0	-0.21	52	52
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.027	0.1	-10000	0	-0.23	45	45
RHOC	0.014	0	-10000	0	-10000	0	0
XIAP	0.01	0.037	-10000	0	-0.42	2	2
MAPK10	-0.065	0.13	-10000	0	-0.3	43	43
DIABLO	0.014	0	-10000	0	-10000	0	0
SMPD2	-0.034	0.1	-10000	0	-0.23	46	46
APH1B	0.01	0.037	-10000	0	-0.42	2	2
APH1A	0.014	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.04	0.11	-10000	0	-0.26	45	45
PSEN1	0.014	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.016	0.038	-10000	0	-0.29	4	4
NT3 (dimer)/p75(NTR)	-0.053	0.12	-10000	0	-0.22	79	79
MAPK8	-0.051	0.12	-10000	0	-0.27	39	39
MAPK9	-0.049	0.12	-10000	0	-0.27	38	38
APAF1	0.007	0.053	-10000	0	-0.42	4	4
NTF3	-0.018	0.083	-10000	0	-0.25	29	29
NTF4	0	0.041	-10000	0	-0.25	7	7
NDN	-0.022	0.12	-10000	0	-0.42	22	22
RAC1/GDP	0.01	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.013	0.081	-10000	0	-0.18	39	39
p75 CTF/Sortilin/TRAF6/NRIF	0.028	0.041	-10000	0	-0.21	8	8
RhoA-B-C/GTP	-0.036	0.1	-10000	0	-0.24	42	42
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.059	0.12	-10000	0	-0.22	74	74
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.07	0.13	-10000	0	-0.24	74	74
PRKACB	0.008	0.048	-10000	0	-0.38	4	4
proBDNF (dimer)/p75 ECD	-0.055	0.12	-10000	0	-0.22	82	82
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.058	0.15	-10000	0	-0.36	51	51
BIRC2	0.004	0.061	-10000	0	-0.39	6	6
neuron projection morphogenesis	-0.041	0.12	0.15	10	-0.26	40	50
BAD	-0.053	0.12	-10000	0	-0.29	39	39
RIPK2	0.014	0	-10000	0	-10000	0	0
NGFR	-0.063	0.14	-10000	0	-0.32	61	61
CYCS	-0.026	0.094	-10000	0	-0.2	46	46
ADAM17	0.014	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.02	0.094	-10000	0	-0.22	39	39
BCL2L11	-0.053	0.12	-10000	0	-0.29	39	39
BDNF (dimer)/p75(NTR)	-0.1	0.15	-10000	0	-0.25	125	125
PI3K	-0.025	0.1	-10000	0	-0.22	42	42
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.027	0.1	-10000	0	-0.23	45	45
NDNL2	0.014	0	-10000	0	-10000	0	0
YWHAE	0.014	0	-10000	0	-10000	0	0
PRKCI	0.009	0.046	-10000	0	-0.42	3	3
NGF (dimer)/p75(NTR)	-0.05	0.12	-10000	0	-0.23	74	74
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.028	0.1	-10000	0	-0.23	46	46
TRAF6	0.014	0	-10000	0	-10000	0	0
RAC1	0.014	0	-10000	0	-10000	0	0
PRKCZ	0.005	0.059	-10000	0	-0.42	5	5
PLG	0	0.016	-10000	0	-0.25	1	1
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.078	0.13	-10000	0	-0.24	85	85
SQSTM1	0.012	0.027	-10000	0	-0.42	1	1
NGFRAP1	0.001	0.074	-10000	0	-0.42	8	8
CASP3	-0.048	0.12	-10000	0	-0.27	39	39
E2F1	0.01	0.037	-10000	0	-0.42	2	2
CASP9	0.014	0	-10000	0	-10000	0	0
IKK complex	-0.034	0.074	-10000	0	-0.26	15	15
NGF (dimer)/TRKA	-0.014	0.088	-10000	0	-0.22	37	37
MMP7	-0.05	0.13	-10000	0	-0.31	51	51
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.018	0.098	-10000	0	-0.21	45	45
MMP3	-0.068	0.14	-10000	0	-0.31	66	66
APAF-1/Caspase 9	-0.06	0.094	-10000	0	-0.3	26	26

×

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	-0.14	0.14	-9999	-0.26	135	135
SMAD6-7/SMURF1	0.025	0.026	-9999	-0.24	2	2
NOG	-0.017	0.082	-9999	-0.25	28	28
SMAD9	-0.034	0.12	-9999	-0.5	13	13
SMAD4	0.014	0	-9999	-10000	0	0
SMAD5	-0.051	0.12	-9999	-0.28	32	32
BMP7/USAG1	-0.15	0.15	-9999	-0.24	170	170
SMAD5/SKI	-0.042	0.11	-9999	-0.26	32	32
SMAD1	0.014	0.052	-9999	-0.31	5	5
BMP2	-0.033	0.12	-9999	-0.32	38	38
SMAD1/SMAD1/SMAD4	-0.004	0.037	-9999	-0.24	5	5
BMPR1A	0.012	0.027	-9999	-0.42	1	1
BMPR1B	-0.12	0.19	-9999	-0.37	89	89
BMPR1A-1B/BAMBI	-0.063	0.13	-9999	-0.26	71	71
AHSG	0.001	0.032	-9999	-0.25	4	4
CER1	0.004	0.006	-9999	-10000	0	0
BMP2-4/CER1	-0.021	0.089	-9999	-0.26	24	24
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.045	0.12	-9999	-0.34	19	19
BMP2-4 (homodimer)	-0.03	0.1	-9999	-0.22	55	55
RGMB	0.012	0.023	-9999	-0.25	2	2
BMP6/BMPR2/BMPR1A-1B	-0.047	0.11	-9999	-0.22	64	64
RGMA	-0.022	0.1	-9999	-0.3	30	30
SMURF1	0.014	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.055	0.12	-9999	-0.28	37	37
BMP2-4/USAG1	-0.086	0.12	-9999	-0.28	57	57
SMAD6/SMURF1/SMAD5	-0.042	0.11	-9999	-0.26	29	29
SOSTDC1	-0.11	0.15	-9999	-0.29	109	109
BMP7/BMPR2/BMPR1A-1B	-0.1	0.14	-9999	-0.26	89	89
SKI	0.014	0	-9999	-10000	0	0
BMP6 (homodimer)	-0.006	0.069	-9999	-0.25	20	20
HFE2	0	0.035	-9999	-0.25	5	5
ZFYVE16	0.009	0.046	-9999	-0.42	3	3
MAP3K7	0.012	0.027	-9999	-0.42	1	1
BMP2-4/CHRD	-0.028	0.1	-9999	-0.26	32	32
SMAD5/SMAD5/SMAD4	-0.042	0.11	-9999	-0.26	29	29
MAPK1	0.014	0	-9999	-10000	0	0
TAK1/TAB family	-0.057	0.091	-9999	-0.26	29	29
BMP7 (homodimer)	-0.12	0.16	-9999	-0.3	110	110
NUP214	0.014	0	-9999	-10000	0	0
BMP6/FETUA	-0.002	0.05	-9999	-0.16	24	24
SMAD1/SKI	0.021	0.05	-9999	-0.29	5	5
SMAD6	0.01	0.035	-9999	-0.3	3	3
CTDSP2	0.014	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.022	0.092	-9999	-0.26	24	24
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.05	0.14	-9999	-0.36	46	46
BMPR2 (homodimer)	0.014	0	-9999	-10000	0	0
GADD34/PP1CA	0.024	0.029	-9999	-0.24	3	3
BMPR1A-1B (homodimer)	-0.071	0.14	-9999	-0.25	89	89
CHRDL1	-0.1	0.18	-9999	-0.35	83	83
ENDOFIN/SMAD1	0.019	0.054	-9999	-0.29	5	5
SMAD6-7/SMURF1/SMAD1	0.031	0.051	-9999	-0.27	5	5
SMAD6/SMURF1	0.014	0	-9999	-10000	0	0
BAMBI	-0.008	0.093	-9999	-0.42	13	13
SMURF2	0.012	0.027	-9999	-0.42	1	1
BMP2-4/CHRDL1	-0.08	0.15	-9999	-0.31	65	65
BMP2-4/GREM1	-0.052	0.12	-9999	-0.27	54	54
SMAD7	0.012	0.027	-9999	-0.42	1	1
SMAD8A/SMAD8A/SMAD4	-0.026	0.11	-9999	-0.46	13	13
SMAD1/SMAD6	0.021	0.05	-9999	-0.29	5	5
TAK1/SMAD6	0.019	0.019	-9999	-0.29	1	1
BMP7	-0.12	0.16	-9999	-0.3	110	110
BMP6	-0.006	0.069	-9999	-0.25	20	20
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.044	0.11	-9999	-0.25	36	36
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	-0.29	1	1
CTDSPL	0.012	0.027	-9999	-0.42	1	1
PPP1CA	0.014	0	-9999	-10000	0	0
XIAP	0.01	0.037	-9999	-0.42	2	2
CTDSP1	0.014	0	-9999	-10000	0	0
PPP1R15A	0.013	0.016	-9999	-0.25	1	1
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.097	0.16	-9999	-0.35	52	52
CHRD	-0.009	0.088	-9999	-0.32	18	18
BMPR2	0.014	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.059	0.12	-9999	-0.3	36	36
BMP4	-0.012	0.092	-9999	-0.32	20	20
FST	-0.094	0.16	-9999	-0.32	86	86
BMP2-4/NOG	-0.032	0.1	-9999	-0.27	29	29
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.09	0.13	-9999	-0.24	89	89

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.01	0.028	-9999	-0.17	6	6
ADCY5	-0.031	0.085	-9999	-0.18	62	62
ADCY6	0.011	0.03	-9999	-0.2	5	5
ADCY7	0.011	0.028	-9999	-0.24	3	3
ADCY1	-0.028	0.094	-9999	-0.24	41	41
ADCY2	-0.087	0.1	-9999	-0.18	137	137
ADCY3	0.013	0.018	-9999	-0.18	2	2
ADCY8	-0.004	0.044	-9999	-0.13	29	29
PRKCE	0.009	0.011	-9999	-0.16	1	1
ADCY9	0.012	0.024	-9999	-0.2	3	3
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.048	0.062	-9999	-0.16	35	35

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.024	0.065	0.32	1	-10000	0	1
SMARCC2	0.014	0.01	-10000	0	-10000	0	0
SMARCC1	0.014	0.01	-10000	0	-10000	0	0
TBX21	-0.14	0.26	-10000	0	-0.65	45	45
SUMO2	0.016	0.008	-10000	0	-10000	0	0
STAT1 (dimer)	0.011	0.055	-10000	0	-0.29	8	8
FKBP4	0.014	0	-10000	0	-10000	0	0
FKBP5	-0.023	0.12	-10000	0	-0.41	23	23
GR alpha/HSP90/FKBP51/HSP90	0.077	0.1	0.23	36	-0.28	5	41
PRL	-0.073	0.11	-10000	0	-0.45	2	2
cortisol/GR alpha (dimer)/TIF2	0.21	0.21	0.47	83	-0.35	1	84
RELA	-0.015	0.069	-10000	0	-0.21	9	9
FGG	0.17	0.18	0.43	55	-10000	0	55
GR beta/TIF2	0.097	0.11	0.26	44	-0.3	6	50
IFNG	-0.35	0.44	-10000	0	-0.9	83	83
apoptosis	0.071	0.14	0.48	18	-10000	0	18
CREB1	0.014	0.011	-10000	0	-10000	0	0
histone acetylation	-0.016	0.13	0.3	9	-0.3	21	30
BGLAP	-0.064	0.12	-10000	0	-0.38	8	8
GR/PKAc	0.097	0.092	0.24	35	-0.28	4	39
NF kappa B1 p50/RelA	-0.021	0.12	-10000	0	-0.3	23	23
SMARCD1	0.014	0.01	-10000	0	-10000	0	0
MDM2	0.082	0.08	0.2	60	-10000	0	60
GATA3	-0.054	0.16	-10000	0	-0.38	47	47
AKT1	0.008	0.001	-10000	0	-10000	0	0
CSF2	-0.05	0.11	-10000	0	-0.43	3	3
GSK3B	0.016	0.008	-10000	0	-10000	0	0
NR1I3	0.08	0.13	0.46	17	-10000	0	17
CSN2	0.14	0.14	0.35	54	-10000	0	54
BRG1/BAF155/BAF170/BAF60A	0.038	0.033	-10000	0	-0.26	3	3
NFATC1	0.001	0.074	-10000	0	-0.42	8	8
POU2F1	0.013	0.015	-10000	0	-10000	0	0
CDKN1A	-0.01	0.19	-10000	0	-1.3	5	5
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.003	0.008	-10000	0	-10000	0	0
SFN	-0.055	0.13	-10000	0	-0.28	61	61
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.054	0.12	0.23	29	-0.25	12	41
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	0.07	0.14	0.44	17	-0.65	2	19
JUN	-0.17	0.16	-10000	0	-0.38	68	68
IL4	-0.088	0.14	-10000	0	-0.46	15	15
CDK5R1	0.005	0.065	-10000	0	-0.42	6	6
PRKACA	0.014	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.073	0.16	0.21	30	-0.35	44	74
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.082	0.096	0.23	34	-0.26	4	38
cortisol/GR alpha (monomer)	0.25	0.25	0.54	85	-10000	0	85
NCOA2	0.003	0.066	-10000	0	-0.4	7	7
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.053	0.071	-10000	0	-0.3	8	8
AP-1/NFAT1-c-4	-0.26	0.27	-10000	0	-0.55	97	97
AFP	-0.12	0.12	-10000	0	-0.49	1	1
SUV420H1	0.012	0.027	-10000	0	-0.42	1	1
IRF1	0.12	0.18	0.37	32	-0.62	7	39
TP53	0.013	0.089	-10000	0	-0.43	10	10
PPP5C	0.014	0	-10000	0	-10000	0	0
KRT17	-0.28	0.34	-10000	0	-0.75	67	67
KRT14	-0.3	0.45	-10000	0	-1.2	47	47
TBP	0.02	0.012	-10000	0	-10000	0	0
CREBBP	0.067	0.1	0.28	43	-0.24	2	45
HDAC1	0.011	0.027	-10000	0	-0.42	1	1
HDAC2	0.013	0.004	-10000	0	-10000	0	0
AP-1	-0.26	0.27	-10000	0	-0.55	98	98
MAPK14	0.016	0.007	-10000	0	-10000	0	0
MAPK10	-0.034	0.12	-10000	0	-0.3	42	42
MAPK11	0.008	0.059	-10000	0	-0.42	5	5
KRT5	-0.36	0.43	-10000	0	-0.99	72	72
interleukin-1 receptor activity	-0.001	0.004	-10000	0	-10000	0	0
NCOA1	0.016	0.001	-10000	0	-10000	0	0
STAT1	0.011	0.055	-10000	0	-0.29	8	8
CGA	-0.077	0.12	-10000	0	-0.39	9	9
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.13	0.13	0.35	50	-10000	0	50
MAPK3	0.016	0.008	-10000	0	-10000	0	0
MAPK1	0.016	0.007	-10000	0	-10000	0	0
ICAM1	-0.12	0.22	-10000	0	-0.61	29	29
NFKB1	-0.015	0.069	-10000	0	-0.22	8	8
MAPK8	-0.14	0.15	-10000	0	-0.33	72	72
MAPK9	0.016	0.007	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.066	0.14	0.48	18	-10000	0	18
BAX	0.01	0.068	-10000	0	-10000	0	0
POMC	-0.2	0.34	-10000	0	-1.2	21	21
EP300	0.067	0.1	0.28	43	-0.24	2	45
cortisol/GR alpha (dimer)/p53	0.22	0.21	0.47	78	-10000	0	78
proteasomal ubiquitin-dependent protein catabolic process	0.058	0.062	0.17	35	-10000	0	35
SGK1	0.1	0.18	-10000	0	-1.2	3	3
IL13	-0.22	0.26	-10000	0	-0.64	49	49
IL6	-0.13	0.22	-10000	0	-0.58	33	33
PRKACG	0.001	0.016	-10000	0	-0.25	1	1
IL5	-0.2	0.22	-10000	0	-0.53	57	57
IL2	-0.22	0.23	-10000	0	-0.59	47	47
CDK5	0.015	0.004	-10000	0	-10000	0	0
PRKACB	0.008	0.048	-10000	0	-0.38	4	4
HSP90AA1	0.012	0.027	-10000	0	-0.42	1	1
IL8	-0.14	0.26	-10000	0	-0.68	34	34
CDK5R1/CDK5	0.016	0.047	-10000	0	-0.29	6	6
NF kappa B1 p50/RelA/PKAc	0.002	0.095	-10000	0	-0.28	11	11
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.22	0.19	0.44	88	-10000	0	88
SMARCA4	0.014	0.01	-10000	0	-10000	0	0
chromatin remodeling	0.14	0.13	0.34	48	-10000	0	48
NF kappa B1 p50/RelA/Cbp	0.052	0.14	0.31	28	-0.34	7	35
JUN (dimer)	-0.17	0.16	-10000	0	-0.38	68	68
YWHAH	0.014	0	-10000	0	-10000	0	0
VIPR1	-0.093	0.17	-10000	0	-0.38	45	45
NR3C1	0.14	0.15	0.36	60	-0.34	3	63
NR4A1	-0.028	0.13	-10000	0	-0.44	21	21
TIF2/SUV420H1	0.011	0.051	-10000	0	-0.27	8	8
MAPKKK cascade	0.071	0.14	0.48	18	-10000	0	18
cortisol/GR alpha (dimer)/Src-1	0.23	0.21	0.47	85	-10000	0	85
PBX1	-0.01	0.079	-10000	0	-0.26	22	22
POU1F1	0.002	0.016	-10000	0	-10000	0	0
SELE	-0.18	0.32	-10000	0	-0.79	46	46
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.14	0.13	0.34	48	-10000	0	48
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.22	0.19	0.44	88	-10000	0	88
mol:cortisol	0.13	0.15	0.32	78	-10000	0	78
MMP1	-0.24	0.38	-10000	0	-1.1	37	37

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.033	0.071	0.2	36	-0.17	1	37
RFC1	0.033	0.071	0.2	36	-0.17	1	37
PRKDC	0.033	0.071	0.2	36	-0.17	1	37
RIPK1	0.014	0.002	-10000	0	-10000	0	0
CASP7	0.027	0.07	0.22	16	-0.31	1	17
FASLG/FAS/FADD/FAF1	0.001	0.11	0.19	29	-0.24	28	57
MAP2K4	-0.008	0.12	-10000	0	-0.28	33	33
mol:ceramide	-0.029	0.14	-10000	0	-0.3	45	45
GSN	0.032	0.073	0.2	36	-0.2	2	38
FASLG/FAS/FADD/FAF1/Caspase 8	-0.003	0.12	0.18	13	-0.27	33	46
FAS	0.007	0.053	-10000	0	-0.42	4	4
BID	0.041	0.088	0.27	32	-0.25	1	33
MAP3K1	0.014	0.085	0.19	14	-0.25	10	24
MAP3K7	0.012	0.027	-10000	0	-0.42	1	1
RB1	0.029	0.079	0.2	36	-0.21	6	42
CFLAR	0.012	0.027	-10000	0	-0.42	1	1
HGF/MET	-0.041	0.12	-10000	0	-0.26	49	49
ARHGDIB	0.027	0.081	0.2	35	-0.22	7	42
FADD	0.012	0.016	-10000	0	-0.25	1	1
actin filament polymerization	-0.032	0.073	0.2	2	-0.2	36	38
NFKB1	-0.007	0.054	-10000	0	-0.26	5	5
MAPK8	-0.008	0.14	-10000	0	-0.44	15	15
DFFA	0.033	0.071	0.2	36	-0.17	1	37
DNA fragmentation during apoptosis	0.033	0.071	0.2	36	-0.17	1	37
FAS/FADD/MET	-0.01	0.088	-10000	0	-0.24	31	31
CFLAR/RIP1	0.019	0.019	-10000	0	-0.29	1	1
FAIM3	-0.051	0.15	-10000	0	-0.37	45	45
FAF1	0.013	0.004	-10000	0	-10000	0	0
PARP1	0.033	0.071	0.2	36	-0.17	1	37
DFFB	0.033	0.071	0.2	36	-0.17	1	37
CHUK	-0.002	0.051	-10000	0	-0.24	5	5
FASLG	-0.077	0.17	-10000	0	-0.37	62	62
FAS/FADD	0.015	0.039	-10000	0	-0.26	5	5
HGF	-0.023	0.11	-10000	0	-0.32	29	29
LMNA	0.035	0.062	0.18	35	-10000	0	35
CASP6	0.033	0.071	0.2	36	-0.17	1	37
CASP10	0.004	0.065	-10000	0	-0.42	6	6
CASP3	0.033	0.087	0.24	36	-0.2	1	37
PTPN13	-0.011	0.1	-10000	0	-0.42	15	15
CASP8	0.044	0.11	0.34	32	-0.3	1	33
IL6	-0.033	0.22	-10000	0	-1.2	8	8
MET	-0.041	0.14	-10000	0	-0.37	38	38
ICAD/CAD	0.035	0.063	0.18	36	-10000	0	36
FASLG/FAS/FADD/FAF1/Caspase 10	-0.03	0.14	-10000	0	-0.31	45	45
activation of caspase activity by cytochrome c	0.041	0.088	0.27	32	-0.25	1	33
PAK2	0.033	0.071	0.2	36	-0.17	1	37
BCL2	0.001	0.074	-10000	0	-0.42	8	8

×

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	-0.021	0.1	-9999	-0.29	30	30
EGF/EGFR	-0.054	0.11	-9999	-0.22	73	73
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.03	0.11	-9999	-0.21	58	58
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.003	0.075	-9999	-0.31	14	14
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.088	0.17	-9999	-0.37	71	71
EGF/EGFR dimer/SHC	-0.053	0.12	-9999	-0.26	58	58
mol:GDP	-0.032	0.1	-9999	-0.21	58	58
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.004	0.079	-9999	-0.34	13	13
GRB2/SOS1	0.02	0	-9999	-10000	0	0
HRAS/GTP	-0.05	0.079	-9999	-0.26	11	11
SHC1	0.014	0	-9999	-10000	0	0
HRAS/GDP	-0.028	0.096	-9999	-0.27	11	11
FRAP1	-0.037	0.094	-9999	-0.2	58	58
EGF/EGFR dimer	-0.074	0.14	-9999	-0.26	90	90
SOS1	0.014	0	-9999	-10000	0	0
GRB2	0.014	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.003	0.079	-9999	-0.23	25	25

×

Endothelins

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
AKT1	0.001	0.16	0.27	22	-0.45	14	36
PTK2B	0.009	0.038	-10000	0	-0.29	4	4
mol:Ca2+	0.021	0.16	-10000	0	-0.72	5	5
EDN1	0.002	0.13	0.2	29	-0.36	16	45
EDN3	-0.11	0.16	-10000	0	-0.32	98	98
EDN2	0.001	0.041	-10000	0	-0.25	7	7
HRAS/GDP	-0.007	0.16	0.2	1	-0.41	25	26
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.007	0.14	0.18	17	-0.4	22	39
ADCY4	-0.039	0.14	0.18	14	-0.33	31	45
ADCY5	-0.071	0.16	0.18	12	-0.36	42	54
ADCY6	-0.039	0.14	0.18	15	-0.33	32	47
ADCY7	-0.039	0.15	0.18	15	-0.34	31	46
ADCY1	-0.069	0.16	0.18	8	-0.35	44	52
ADCY2	-0.12	0.17	0.18	9	-0.36	60	69
ADCY3	-0.037	0.14	0.18	15	-0.34	30	45
ADCY8	-0.051	0.15	0.18	13	-0.35	31	44
ADCY9	-0.038	0.14	0.18	15	-0.34	30	45
arachidonic acid secretion	0.008	0.14	-10000	0	-0.41	15	15
ETB receptor/Endothelin-1/Gq/GTP	0.002	0.099	-10000	0	-0.27	22	22
GNAO1	-0.068	0.17	-10000	0	-0.41	51	51
HRAS	0.014	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	0.034	0.17	0.33	30	-0.41	14	44
ETA receptor/Endothelin-1/Gs/GTP	-0.009	0.18	0.3	28	-0.36	29	57
mol:GTP	0.002	0.002	-10000	0	-10000	0	0
COL3A1	-0.012	0.19	0.27	22	-0.51	20	42
EDNRB	-0.004	0.085	-10000	0	-0.42	10	10
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.03	0.21	0.27	22	-0.51	29	51
CYSLTR1	-0.012	0.19	0.27	22	-0.52	21	43
SLC9A1	0.01	0.097	0.19	22	-0.28	10	32
mol:GDP	-0.015	0.17	0.2	8	-0.43	27	35
SLC9A3	-0.033	0.21	-10000	0	-0.54	29	29
RAF1	-0.007	0.15	-10000	0	-0.45	17	17
JUN	0.025	0.14	-10000	0	-0.73	3	3
JAK2	-0.004	0.17	0.27	22	-0.44	17	39
mol:IP3	-0.01	0.14	-10000	0	-0.4	23	23
ETA receptor/Endothelin-1	0.023	0.21	0.39	30	-0.44	20	50
PLCB1	-0.028	0.13	-10000	0	-0.4	27	27
PLCB2	0	0.079	-10000	0	-0.42	9	9
ETA receptor/Endothelin-3	-0.075	0.14	-10000	0	-0.27	67	67
FOS	0.012	0.13	-10000	0	-0.43	8	8
Gai/GDP	-0.1	0.25	-10000	0	-0.62	48	48
CRK	0.014	0	-10000	0	-10000	0	0
mol:Ca ++	-0.018	0.19	0.24	17	-0.5	25	42
BCAR1	0.011	0.037	-10000	0	-0.42	2	2
PRKCB1	-0.009	0.14	-10000	0	-0.38	23	23
GNAQ	0.016	0.002	-10000	0	-10000	0	0
GNAZ	-0.029	0.12	-10000	0	-0.39	28	28
GNAL	-0.069	0.15	-10000	0	-0.32	66	66
Gs family/GDP	-0.049	0.16	-10000	0	-0.41	30	30
ETA receptor/Endothelin-1/Gq/GTP	0.01	0.13	0.2	20	-0.34	19	39
MAPK14	-0.007	0.11	-10000	0	-0.32	21	21
TRPC6	0.02	0.16	-10000	0	-0.78	5	5
GNAI2	0.014	0	-10000	0	-10000	0	0
GNAI3	0.014	0	-10000	0	-10000	0	0
GNAI1	0.009	0.046	-10000	0	-0.42	3	3
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.012	0.12	-10000	0	-0.34	22	22
ETB receptor/Endothelin-2	0	0.067	-10000	0	-0.3	10	10
ETB receptor/Endothelin-3	-0.078	0.13	-10000	0	-0.29	53	53
ETB receptor/Endothelin-1	0.002	0.12	-10000	0	-0.31	23	23
MAPK3	0.007	0.14	-10000	0	-0.46	12	12
MAPK1	0.007	0.14	-10000	0	-0.46	12	12
Rac1/GDP	-0.007	0.16	0.2	1	-0.42	24	25
cAMP biosynthetic process	-0.095	0.17	0.2	6	-0.36	54	60
MAPK8	0.016	0.16	-10000	0	-0.63	9	9
SRC	0.012	0.026	-10000	0	-0.42	1	1
ETB receptor/Endothelin-1/Gi/GTP	-0.037	0.12	-10000	0	-0.27	33	33
p130Cas/CRK/Src/PYK2	-0.002	0.16	-10000	0	-0.49	18	18
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.007	0.16	0.2	1	-0.41	25	26
COL1A2	-0.015	0.22	0.27	21	-0.61	19	40
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	0.004	0.095	-10000	0	-0.3	11	11
mol:DAG	-0.01	0.14	-10000	0	-0.39	23	23
MAP2K2	0.002	0.14	-10000	0	-0.46	13	13
MAP2K1	0.002	0.14	-10000	0	-0.43	16	16
EDNRA	0.001	0.13	0.21	22	-0.34	17	39
positive regulation of muscle contraction	0.008	0.14	0.23	22	-0.4	13	35
Gq family/GDP	-0.045	0.14	-10000	0	-0.46	20	20
HRAS/GTP	-0.016	0.16	-10000	0	-0.43	22	22
PRKCH	-0.005	0.14	-10000	0	-0.39	22	22
RAC1	0.014	0	-10000	0	-10000	0	0
PRKCA	-0.013	0.14	-10000	0	-0.38	24	24
PRKCB	-0.029	0.17	-10000	0	-0.38	37	37
PRKCE	-0.004	0.14	-10000	0	-0.39	20	20
PRKCD	-0.005	0.14	-10000	0	-0.39	21	21
PRKCG	-0.009	0.14	-10000	0	-0.4	21	21
regulation of vascular smooth muscle contraction	0.01	0.14	-10000	0	-0.5	8	8
PRKCQ	-0.038	0.18	-10000	0	-0.38	39	39
PLA2G4A	0.006	0.15	-10000	0	-0.44	15	15
GNA14	-0.026	0.1	-10000	0	-0.27	39	39
GNA15	-0.002	0.082	-10000	0	-0.39	11	11
GNA12	0.014	0	-10000	0	-10000	0	0
GNA11	0.015	0.002	-10000	0	-10000	0	0
Rac1/GTP	0.034	0.17	0.33	30	-0.41	14	44
MMP1	-0.12	0.29	0.27	2	-0.79	37	39

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.067	0.27	-9999	-0.94	21	21
MKNK1	0.014	0	-9999	-10000	0	0
MAPK14	-0.013	0.097	-9999	-0.28	26	26
ATF2/c-Jun	-0.003	0.095	-9999	-0.46	4	4
MAPK11	-0.022	0.12	-9999	-0.32	31	31
MITF	-0.046	0.16	-9999	-0.32	57	57
MAPKAPK5	-0.015	0.12	-9999	-0.33	31	31
KRT8	-0.06	0.16	-9999	-0.34	54	54
MAPKAPK3	0.014	0	-9999	-10000	0	0
MAPKAPK2	0.014	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.025	0.15	-9999	-0.41	31	31
CEBPB	-0.015	0.12	-9999	-0.33	31	31
SLC9A1	-0.015	0.12	-9999	-0.33	31	31
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.014	0.13	-9999	-0.34	32	32
p38alpha-beta/MNK1	-0.008	0.12	-9999	-0.33	27	27
JUN	-0.003	0.094	-9999	-0.46	4	4
PPARGC1A	-0.1	0.19	-9999	-0.34	89	89
USF1	-0.015	0.12	-9999	-0.33	31	31
RAB5/GDP/GDI1	-0.007	0.088	-9999	-0.25	27	27
NOS2	-0.043	0.21	-9999	-0.92	11	11
DDIT3	-0.015	0.12	-9999	-0.33	31	31
RAB5A	0.014	0	-9999	-10000	0	0
HSPB1	-0.007	0.1	-9999	-0.28	27	27
p38alpha-beta/HBP1	-0.008	0.12	-9999	-0.33	27	27
CREB1	-0.016	0.14	-9999	-0.37	31	31
RAB5/GDP	0.01	0	-9999	-10000	0	0
EIF4E	-0.008	0.1	-9999	-0.29	27	27
RPS6KA4	-0.015	0.12	-9999	-0.33	31	31
PLA2G4A	-0.018	0.12	-9999	-0.31	29	29
GDI1	-0.015	0.12	-9999	-0.33	31	31
TP53	-0.027	0.15	-9999	-0.4	31	31
RPS6KA5	-0.02	0.14	-9999	-0.35	33	33
ESR1	-0.028	0.15	-9999	-0.37	37	37
HBP1	0.014	0	-9999	-10000	0	0
MEF2C	-0.021	0.14	-9999	-0.35	34	34
MEF2A	-0.018	0.13	-9999	-0.36	31	31
EIF4EBP1	-0.016	0.14	-9999	-0.37	31	31
KRT19	-0.048	0.14	-9999	-0.34	42	42
ELK4	-0.015	0.12	-9999	-0.33	31	31
ATF6	-0.015	0.12	-9999	-0.33	31	31
ATF1	-0.016	0.14	-9999	-0.37	31	31
p38alpha-beta/MAPKAPK2	-0.008	0.12	-9999	-0.33	27	27
p38alpha-beta/MAPKAPK3	-0.008	0.12	-9999	-0.33	27	27

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.025	0.12	-9999	-0.36	27	27
GPC2	-0.013	0.1	-9999	-0.37	19	19
GPC2/Midkine	-0.025	0.11	-9999	-0.31	30	30
neuron projection morphogenesis	-0.025	0.11	-9999	-0.31	30	30

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	-0.036	0.15	0.17	2	-0.38	36	38
ACTA1	-0.055	0.19	0.17	12	-0.47	36	48
NUMA1	-0.036	0.15	0.17	2	-0.38	35	37
SPTAN1	-0.051	0.18	0.17	12	-0.46	36	48
LIMK1	-0.051	0.18	0.17	11	-0.46	36	47
BIRC3	-0.058	0.15	-10000	0	-0.36	51	51
BIRC2	0.004	0.061	-10000	0	-0.39	6	6
BAX	0.014	0	-10000	0	-10000	0	0
CASP10	-0.065	0.16	-10000	0	-0.36	53	53
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.01	0.038	-10000	0	-0.42	2	2
PTK2	-0.036	0.15	0.17	2	-0.38	35	37
DIABLO	0.014	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.05	0.18	0.17	12	-0.45	36	48
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.013	0.016	-10000	0	-0.25	1	1
GSN	-0.053	0.19	0.17	11	-0.47	36	47
MADD	0.014	0	-10000	0	-10000	0	0
TFAP2A	-0.077	0.23	-10000	0	-0.59	40	40
BID	-0.031	0.095	-10000	0	-0.23	41	41
MAP3K1	-0.02	0.088	-10000	0	-0.23	28	28
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	0.038	-10000	0	-0.29	4	4
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.057	0.2	0.17	11	-0.49	36	47
CASP9	0.014	0	-10000	0	-10000	0	0
DNA repair	-0.008	0.056	0.14	11	-0.16	16	27
neuron apoptosis	-0.018	0.13	-10000	0	-0.62	12	12
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.043	0.18	0.18	3	-0.45	35	38
APAF1	0.007	0.053	-10000	0	-0.42	4	4
CASP6	-0.016	0.1	-10000	0	-0.32	21	21
TRAF2	0.014	0	-10000	0	-10000	0	0
ICAD/CAD	-0.045	0.18	0.17	11	-0.44	36	47
CASP7	0.04	0.097	0.28	33	-10000	0	33
KRT18	-0.065	0.19	-10000	0	-0.57	31	31
apoptosis	-0.03	0.15	0.18	12	-0.37	35	47
DFFA	-0.051	0.18	0.17	12	-0.46	36	48
DFFB	-0.051	0.18	0.17	12	-0.46	36	48
PARP1	0.008	0.056	0.17	16	-0.14	11	27
actin filament polymerization	0.044	0.17	0.42	36	-0.17	11	47
TNF	-0.025	0.11	-10000	0	-0.34	29	29
CYCS	-0.022	0.069	-10000	0	-0.19	28	28
SATB1	-0.029	0.13	-10000	0	-0.39	19	19
SLK	-0.055	0.18	0.17	12	-0.45	38	50
p15 BID/BAX	-0.021	0.086	-10000	0	-0.25	24	24
CASP2	-0.001	0.083	-10000	0	-0.31	9	9
JNK cascade	0.02	0.087	0.23	28	-10000	0	28
CASP3	-0.059	0.2	0.18	12	-0.42	46	58
LMNB2	0.001	0.077	-10000	0	-0.29	10	10
RIPK1	0.014	0	-10000	0	-10000	0	0
CASP4	0.009	0.046	-10000	0	-0.42	3	3
Mammalian IAPs/DIABLO	-0.01	0.1	-10000	0	-0.24	35	35
negative regulation of DNA binding	-0.076	0.22	-10000	0	-0.58	40	40
stress fiber formation	-0.053	0.18	0.17	12	-0.44	38	50
GZMB	-0.078	0.18	-10000	0	-0.33	74	74
CASP1	-0.007	0.081	-10000	0	-0.3	17	17
LMNB1	0.001	0.077	-10000	0	-0.29	10	10
APP	-0.018	0.14	-10000	0	-0.63	12	12
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	-0.029	0.15	0.19	13	-0.36	33	46
LMNA	0	0.081	-10000	0	-0.28	13	13
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.005	0.087	-10000	0	-0.33	9	9
LRDD	0.004	0.064	-10000	0	-0.42	6	6
SREBF1	-0.052	0.18	0.17	12	-0.45	37	49
APAF-1/Caspase 9	0.01	0.065	0.35	5	-0.24	1	6
nuclear fragmentation during apoptosis	-0.035	0.15	0.17	2	-0.38	35	37
CFL2	-0.046	0.18	0.17	11	-0.43	36	47
GAS2	-0.082	0.19	0.17	11	-0.39	56	67
positive regulation of apoptosis	0.004	0.078	-10000	0	-0.29	10	10
PRF1	-0.05	0.14	-10000	0	-0.36	45	45

×

Nectin adhesion pathway

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
PDGFRB	0.01	0.037	-9999	-0.42	2	2
alphaV beta3 Integrin	-0.037	0.12	-9999	-0.27	52	52
PTK2	-0.037	0.14	-9999	-0.34	38	38
positive regulation of JNK cascade	-0.044	0.099	-9999	-0.27	41	41
CDC42/GDP	-0.023	0.15	-9999	-0.36	40	40
Rac1/GDP	-0.021	0.15	-9999	-0.36	39	39
RAP1B	0.013	0.016	-9999	-0.25	1	1
RAP1A	0.014	0	-9999	-10000	0	0
CTNNB1	0.014	0	-9999	-10000	0	0
CDC42/GTP	-0.052	0.12	-9999	-0.33	41	41
nectin-3/I-afadin	-0.027	0.11	-9999	-0.28	42	42
RAPGEF1	-0.03	0.16	-9999	-0.4	39	39
mol:GTP	0	0	-9999	-10000	0	0
CRK	-0.041	0.17	-9999	-0.45	39	39
PDGFB-D/PDGFRB	0.01	0.037	-9999	-0.42	2	2
TLN1	0.001	0.056	-9999	-0.24	2	2
Rap1/GTP	-0.044	0.1	-9999	-0.28	39	39
IQGAP1	0.014	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.024	0.024	-9999	-0.21	2	2
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.027	0.11	-9999	-0.28	42	42
PVR	0.01	0.037	-9999	-0.42	2	2
Necl-5(dimer)	0.01	0.037	-9999	-0.42	2	2
mol:GDP	-0.037	0.18	-9999	-0.44	40	40
MLLT4	0.009	0.041	-9999	-0.36	3	3
PIK3CA	0.008	0.048	-9999	-0.38	4	4
PI3K	-0.001	0.097	-9999	-0.21	40	40
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.015	0.036	-9999	-0.24	5	5
positive regulation of lamellipodium assembly	-0.049	0.11	-9999	-0.28	44	44
PVRL1	0.011	0.031	-9999	-0.33	2	2
PVRL3	-0.049	0.15	-9999	-0.4	40	40
PVRL2	0.014	0	-9999	-10000	0	0
PIK3R1	0.01	0.037	-9999	-0.42	2	2
CDH1	-0.13	0.2	-9999	-0.39	92	92
CLDN1	-0.13	0.18	-9999	-0.32	114	114
JAM-A/CLDN1	-0.084	0.14	-9999	-0.26	82	82
SRC	-0.051	0.19	-9999	-0.5	39	39
ITGB3	-0.058	0.16	-9999	-0.38	49	49
nectin-1(dimer)/I-afadin/I-afadin	0.015	0.036	-9999	-0.24	5	5
FARP2	-0.037	0.17	-9999	-0.44	40	40
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)	-0.015	0.097	-9999	-0.24	39	39
nectin-1/I-afadin	0.015	0.036	-9999	-0.24	5	5
nectin-2/I-afadin	0.017	0.029	-9999	-0.24	3	3
RAC1/GTP/IQGAP1/filamentous actin	0.019	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.014	0.097	-9999	-0.24	38	38
CDC42/GTP/IQGAP1/filamentous actin	0.019	0	-9999	-10000	0	0
F11R	0.005	0.059	-9999	-0.42	5	5
positive regulation of filopodium formation	-0.044	0.099	-9999	-0.27	41	41
alphaV/beta3 Integrin/Talin	-0.022	0.095	-9999	-0.2	41	41
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.017	0.029	-9999	-0.24	3	3
nectin-2(dimer)/I-afadin/I-afadin	0.017	0.029	-9999	-0.24	3	3
PIP5K1C	-0.005	0.06	-9999	-0.15	38	38
VAV2	-0.046	0.19	-9999	-0.45	44	44
RAP1/GDP	-0.018	0.14	-9999	-0.34	39	39
ITGAV	0.004	0.061	-9999	-0.39	6	6
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.013	0.095	-9999	-0.24	37	37
nectin-3(dimer)/I-afadin/I-afadin	-0.027	0.11	-9999	-0.28	42	42
Rac1/GTP	-0.058	0.13	-9999	-0.34	44	44
PTPRM	-0.012	0.067	-9999	-0.17	38	38
E-cadherin/beta catenin/alpha catenin	-0.032	0.1	-9999	-0.18	79	79
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.014	0	-9999	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.013	0.016	-9999	-0.25	1	1
ITGB7	-0.013	0.1	-9999	-0.41	17	17
ITGA4	-0.031	0.13	-9999	-0.38	30	30
alpha4/beta7 Integrin	-0.03	0.12	-9999	-0.29	43	43
alpha4/beta1 Integrin	-0.012	0.09	-9999	-0.26	31	31

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	0.011	0.044	-9999	-0.18	13	13
alphaV beta3 Integrin	-0.074	0.16	-9999	-0.31	72	72
PTK2	-0.071	0.16	-9999	-0.39	45	45
IGF1R	0.009	0.041	-9999	-0.36	3	3
PI4KB	0.014	0	-9999	-10000	0	0
MFGE8	0.01	0.035	-9999	-0.3	3	3
SRC	0.012	0.027	-9999	-0.42	1	1
CDKN1B	-0.037	0.09	-9999	-0.32	10	10
VEGFA	0.004	0.052	-9999	-0.27	9	9
ILK	-0.037	0.09	-9999	-0.32	10	10
ROCK1	0.005	0.059	-9999	-0.42	5	5
AKT1	-0.028	0.084	-9999	-0.31	9	9
PTK2B	-0.018	0.093	-9999	-0.21	44	44
alphaV/beta3 Integrin/JAM-A	-0.074	0.15	-9999	-0.28	82	82
CBL	0.014	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.025	0.1	-9999	-0.26	39	39
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0	0.086	-9999	-0.21	34	34
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.018	0.099	-9999	-0.29	15	15
alphaV/beta3 Integrin/Syndecan-1	-0.033	0.12	-9999	-0.26	47	47
PI4KA	0.013	0.016	-9999	-0.25	1	1
IGF-1R heterotetramer/IGF1/IRS1	-0.1	0.15	-9999	-0.41	36	36
PI4 Kinase	0.02	0.011	-9999	-0.16	1	1
PIK3CA	0.008	0.048	-9999	-0.38	4	4
alphaV/beta3 Integrin/Osteopontin	-0.059	0.14	-9999	-0.28	65	65
RPS6KB1	-0.073	0.15	-9999	-0.39	36	36
TLN1	0.014	0	-9999	-10000	0	0
MAPK3	-0.13	0.24	-9999	-0.49	72	72
GPR124	0.007	0.053	-9999	-0.42	4	4
MAPK1	-0.13	0.24	-9999	-0.49	72	72
PXN	0.014	0	-9999	-10000	0	0
PIK3R1	0.01	0.037	-9999	-0.42	2	2
alphaV/beta3 Integrin/Tumstatin	-0.058	0.13	-9999	-0.28	52	52
cell adhesion	-0.018	0.1	-9999	-0.25	40	40
ANGPTL3	0.007	0.007	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src	0.019	0.04	-9999	-0.24	3	3
IGF-1R heterotetramer	0.009	0.041	-9999	-0.36	3	3
Rac1/GDP	0.01	0	-9999	-10000	0	0
TGFBR2	0.013	0.016	-9999	-0.25	1	1
ITGB3	-0.058	0.16	-9999	-0.38	49	49
IGF1	-0.023	0.12	-9999	-0.38	25	25
RAC1	0.014	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.025	0.11	-9999	-0.25	43	43
apoptosis	0.004	0.061	-9999	-0.39	6	6
CD47	0.014	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.021	0.1	-9999	-0.25	39	39
VCL	0.014	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.068	0.14	-9999	-0.3	62	62
CSF1	0.002	0.069	-9999	-0.42	7	7
PIK3C2A	-0.047	0.13	-9999	-0.48	14	14
PI4 Kinase/Pyk2	-0.08	0.12	-9999	-0.32	38	38
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.017	0.1	-9999	-0.22	43	43
FAK1/Vinculin	-0.051	0.13	-9999	-0.33	36	36
alphaV beta3/Integrin/ppsTEM5	-0.025	0.11	-9999	-0.25	43	43
RHOA	0.014	0	-9999	-10000	0	0
VTN	-0.029	0.1	-9999	-0.27	39	39
BCAR1	0.01	0.037	-9999	-0.42	2	2
FGF2	-0.079	0.18	-9999	-0.4	59	59
F11R	-0.052	0.13	-9999	-0.28	63	63
alphaV/beta3 Integrin/Lactadherin	-0.023	0.1	-9999	-0.25	40	40
alphaV/beta3 Integrin/TGFBR2	-0.021	0.11	-9999	-0.26	39	39
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.022	0.055	-9999	-0.21	14	14
HSP90AA1	0.012	0.027	-9999	-0.42	1	1
alphaV/beta3 Integrin/Talin	-0.018	0.095	-9999	-0.23	39	39
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.014	0.1	-9999	-0.4	18	18
alphaV/beta3 Integrin/Pyk2	-0.014	0.096	-9999	-0.21	44	44
SDC1	-0.008	0.089	-9999	-0.36	15	15
VAV3	0.003	0.074	-9999	-0.22	20	20
PTPN11	0.014	0	-9999	-10000	0	0
IRS1	-0.009	0.095	-9999	-0.41	14	14
FAK1/Paxillin	-0.051	0.13	-9999	-0.33	36	36
cell migration	-0.042	0.12	-9999	-0.31	31	31
ITGAV	0.004	0.061	-9999	-0.39	6	6
PI3K	-0.064	0.15	-9999	-0.37	37	37
SPP1	-0.053	0.15	-9999	-0.36	47	47
KDR	0.009	0.038	-9999	-0.29	4	4
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.004	0.061	-9999	-0.39	6	6
COL4A3	-0.052	0.13	-9999	-0.3	54	54
angiogenesis	-0.13	0.24	-9999	-0.49	75	75
Rac1/GTP	0.01	0.069	-9999	-0.2	20	20
EDIL3	-0.069	0.15	-9999	-0.32	65	65
cell proliferation	-0.021	0.1	-9999	-0.26	39	39

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.007	0.053	-10000	0	-0.42	4	4
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.092	0.24	0.58	35	-10000	0	35
IL27/IL27R/JAK1	-0.092	0.26	-10000	0	-0.87	20	20
TBX21	-0.12	0.23	-10000	0	-0.51	53	53
IL12B	-0.001	0.047	-10000	0	-0.25	9	9
IL12A	-0.019	0.08	-10000	0	-0.25	27	27
IL6ST	-0.018	0.1	-10000	0	-0.43	16	16
IL27RA/JAK1	-0.049	0.24	-10000	0	-1.2	12	12
IL27	-0.021	0.1	-10000	0	-0.4	18	18
TYK2	0.008	0.012	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.006	0.065	-10000	0	-0.57	1	1
T-helper 2 cell differentiation	0.092	0.24	0.58	35	-10000	0	35
T cell proliferation during immune response	0.092	0.24	0.58	35	-10000	0	35
MAPKKK cascade	-0.092	0.24	-10000	0	-0.58	35	35
STAT3	0.014	0	-10000	0	-10000	0	0
STAT2	0.014	0	-10000	0	-10000	0	0
STAT1	0.01	0.037	-10000	0	-0.42	2	2
IL12RB1	-0.042	0.14	-10000	0	-0.4	35	35
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.13	0.24	-10000	0	-0.47	72	72
IL27/IL27R/JAK2/TYK2	-0.094	0.25	-10000	0	-0.6	35	35
positive regulation of T cell mediated cytotoxicity	-0.092	0.24	-10000	0	-0.58	35	35
STAT1 (dimer)	-0.16	0.28	0.36	2	-0.78	31	33
JAK2	0.001	0.062	-10000	0	-0.4	6	6
JAK1	0.013	0.002	-10000	0	-10000	0	0
STAT2 (dimer)	-0.083	0.23	-10000	0	-0.57	34	34
T cell proliferation	-0.098	0.24	-10000	0	-0.6	34	34
IL12/IL12R/TYK2/JAK2	-0.072	0.16	-10000	0	-0.45	22	22
IL17A	-0.006	0.065	-10000	0	-0.57	1	1
mast cell activation	0.092	0.24	0.58	35	-10000	0	35
IFNG	-0.027	0.054	-10000	0	-0.12	61	61
T cell differentiation	-0.007	0.009	-10000	0	-0.021	71	71
STAT3 (dimer)	-0.083	0.23	-10000	0	-0.57	34	34
STAT5A (dimer)	-0.085	0.23	-10000	0	-0.56	35	35
STAT4 (dimer)	-0.1	0.25	-10000	0	-0.57	40	40
STAT4	-0.031	0.12	-10000	0	-0.35	33	33
T cell activation	-0.001	0.027	0.12	13	-10000	0	13
IL27R/JAK2/TYK2	-0.062	0.25	-10000	0	-0.88	18	18
GATA3	-0.15	0.42	-10000	0	-1.2	37	37
IL18	-0.02	0.084	-10000	0	-0.26	28	28
positive regulation of mast cell cytokine production	-0.081	0.22	-10000	0	-0.55	34	34
IL27/EBI3	-0.037	0.13	-10000	0	-0.33	38	38
IL27RA	-0.057	0.26	-10000	0	-1.2	12	12
IL6	-0.018	0.098	-10000	0	-0.3	27	27
STAT5A	0.01	0.037	-10000	0	-0.42	2	2
monocyte differentiation	-0.001	0.003	-10000	0	-10000	0	0
IL2	0.02	0.1	0.48	12	-10000	0	12
IL1B	-0.032	0.096	-10000	0	-0.24	43	43
EBI3	-0.033	0.13	-10000	0	-0.4	28	28
TNF	-0.018	0.078	-10000	0	-0.23	29	29

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	-0.001	0.073	-10000	0	-0.34	11	11
GNB1/GNG2	-0.045	0.075	-10000	0	-0.19	52	52
AKT1	-0.011	0.099	-10000	0	-0.2	51	51
EGF	-0.088	0.17	-10000	0	-0.37	71	71
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.002	0.084	-10000	0	-0.31	10	10
mol:Ca2+	-0.034	0.14	-10000	0	-0.31	53	53
LYN	0.008	0.072	-10000	0	-0.33	5	5
RhoA/GTP	-0.026	0.051	-10000	0	-0.12	53	53
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.042	0.17	-10000	0	-0.35	55	55
GNG2	-0.003	0.082	-10000	0	-0.42	10	10
ARRB2	0.014	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.002	0.09	-10000	0	-0.37	13	13
G beta5/gamma2	-0.059	0.1	-10000	0	-0.25	52	52
PRKCH	-0.041	0.16	-10000	0	-0.35	53	53
DNM1	-0.002	0.074	-10000	0	-0.33	12	12
TXA2/TP beta/beta Arrestin3	-0.007	0.032	-10000	0	-0.22	2	2
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	-0.011	0.094	-10000	0	-0.36	17	17
G12 family/GTP	-0.067	0.12	-10000	0	-0.3	53	53
ADRBK1	0.014	0	-10000	0	-10000	0	0
ADRBK2	0.001	0.074	-10000	0	-0.42	8	8
RhoA/GTP/ROCK1	0.013	0.035	-10000	0	-0.24	5	5
mol:GDP	0.024	0.12	0.31	24	-10000	0	24
mol:NADP	0.004	0.059	-10000	0	-0.35	7	7
RAB11A	0.014	0	-10000	0	-10000	0	0
PRKG1	-0.02	0.11	-10000	0	-0.36	24	24
mol:IP3	-0.048	0.18	-10000	0	-0.39	53	53
cell morphogenesis	0.013	0.035	-10000	0	-0.24	5	5
PLCB2	-0.075	0.24	-10000	0	-0.53	53	53
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.029	0.094	-10000	0	-0.32	12	12
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.001	0.088	-10000	0	-0.32	11	11
RHOA	0.014	0	-10000	0	-10000	0	0
PTGIR	0.009	0.046	-10000	0	-0.42	3	3
PRKCB1	-0.047	0.17	-10000	0	-0.38	53	53
GNAQ	0.014	0	-10000	0	-10000	0	0
mol:L-citrulline	0.004	0.059	-10000	0	-0.35	7	7
TXA2/TXA2-R family	-0.075	0.24	-10000	0	-0.53	53	53
LCK	-0.022	0.11	-10000	0	-0.28	28	28
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.003	0.064	-10000	0	-0.21	11	11
TXA2-R family/G12 family/GDP/G beta/gamma	0.017	0.034	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.01	0.064	-10000	0	-0.24	6	6
MAPK14	-0.02	0.11	-10000	0	-0.23	54	54
TGM2/GTP	-0.056	0.2	-10000	0	-0.44	53	53
MAPK11	-0.022	0.12	-10000	0	-0.23	56	56
ARHGEF1	-0.012	0.086	-10000	0	-0.18	53	53
GNAI2	0.014	0	-10000	0	-10000	0	0
JNK cascade	-0.048	0.18	-10000	0	-0.39	53	53
RAB11/GDP	0.014	0.001	-10000	0	-10000	0	0
ICAM1	-0.032	0.14	-10000	0	-0.3	52	52
cAMP biosynthetic process	-0.046	0.16	-10000	0	-0.36	53	53
Gq family/GTP/EBP50	0.005	0.052	-10000	0	-0.2	14	14
actin cytoskeleton reorganization	0.013	0.035	-10000	0	-0.24	5	5
SRC	0.01	0.067	-10000	0	-0.3	5	5
GNB5	0.006	0.055	-10000	0	-0.39	5	5
GNB1	0.014	0	-10000	0	-10000	0	0
EGF/EGFR	-0.042	0.12	-10000	0	-0.29	35	35
VCAM1	-0.039	0.15	-10000	0	-0.32	53	53
TP beta/Gq family/GDP/G beta5/gamma2	-0.002	0.09	-10000	0	-0.37	13	13
platelet activation	-0.026	0.15	-10000	0	-0.3	53	53
PGI2/IP	0.007	0.032	-10000	0	-0.3	3	3
PRKACA	0.004	0.053	-10000	0	-0.21	14	14
Gq family/GDP/G beta5/gamma2	0	0.083	-10000	0	-0.34	13	13
TXA2/TP beta/beta Arrestin2	-0.014	0.068	-10000	0	-0.45	6	6
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.003	0.071	-10000	0	-0.22	23	23
mol:DAG	-0.055	0.19	-10000	0	-0.43	53	53
EGFR	-0.021	0.1	-10000	0	-0.29	30	30
TXA2/TP alpha	-0.068	0.22	-10000	0	-0.5	53	53
Gq family/GTP	-0.013	0.045	-10000	0	-0.19	13	13
YES1	0.008	0.068	-10000	0	-0.28	5	5
GNAI2/GTP	-0.022	0.061	-10000	0	-0.28	6	6
PGD2/DP	-0.007	0.065	-10000	0	-0.25	17	17
SLC9A3R1	0.011	0.031	-10000	0	-0.33	2	2
FYN	0.01	0.065	-10000	0	-0.3	4	4
mol:NO	0.004	0.059	-10000	0	-0.35	7	7
GNA15	-0.003	0.081	-10000	0	-0.39	11	11
PGK/cGMP	-0.007	0.076	-10000	0	-0.26	19	19
RhoA/GDP	0.014	0.001	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0.004	0.087	-10000	0	-0.4	5	5
NOS3	0.004	0.059	-10000	0	-0.35	7	7
RAC1	0.014	0	-10000	0	-10000	0	0
PRKCA	-0.045	0.16	-10000	0	-0.35	53	53
PRKCB	-0.054	0.18	-10000	0	-0.38	53	53
PRKCE	-0.038	0.16	-10000	0	-0.35	53	53
PRKCD	-0.045	0.17	-10000	0	-0.38	53	53
PRKCG	-0.049	0.18	-10000	0	-0.39	53	53
muscle contraction	-0.068	0.22	-10000	0	-0.5	53	53
PRKCZ	-0.04	0.16	-10000	0	-0.34	53	53
ARR3	0	0.022	-10000	0	-0.25	2	2
TXA2/TP beta	0.003	0.078	-10000	0	-0.22	19	19
PRKCQ	-0.059	0.18	-10000	0	-0.4	53	53
MAPKKK cascade	-0.066	0.21	-10000	0	-0.47	53	53
SELE	-0.045	0.16	-10000	0	-0.34	53	53
TP beta/GNAI2/GDP/G beta/gamma	0.011	0.073	-10000	0	-0.31	3	3
ROCK1	0.005	0.059	-10000	0	-0.42	5	5
GNA14	-0.028	0.1	-10000	0	-0.27	39	39
chemotaxis	-0.087	0.26	-10000	0	-0.61	52	52
GNA12	0.014	0	-10000	0	-10000	0	0
GNA13	0.014	0	-10000	0	-10000	0	0
GNA11	0.014	0	-10000	0	-10000	0	0
Rac1/GTP	0.01	0.001	-10000	0	-10000	0	0

×

HIF-1-alpha transcription factor network

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
PKM2	-0.12	0.35	-9999	-0.77	34	34
HDAC7	0.013	0.027	-9999	-0.42	1	1
HIF1A/ARNT/Cbp/p300/Src-1	-0.073	0.31	-9999	-0.72	23	23
SMAD4	0.015	0	-9999	-10000	0	0
ID2	-0.12	0.35	-9999	-0.77	34	34
AP1	0.015	0.035	-9999	-0.31	1	1
ABCG2	-0.12	0.36	-9999	-0.77	37	37
HIF1A	-0.008	0.064	-9999	-10000	0	0
TFF3	-0.16	0.38	-9999	-0.78	47	47
GATA2	0	0.072	-9999	-0.33	11	11
AKT1	-0.016	0.074	-9999	-0.22	4	4
response to hypoxia	-0.03	0.076	-9999	-0.19	13	13
MCL1	-0.12	0.35	-9999	-0.76	35	35
NDRG1	-0.12	0.36	-9999	-0.78	35	35
SERPINE1	-0.12	0.36	-9999	-0.81	35	35
FECH	-0.12	0.35	-9999	-0.77	34	34
FURIN	-0.12	0.35	-9999	-0.77	34	34
NCOA2	0.004	0.066	-9999	-0.4	7	7
EP300	-0.013	0.11	-9999	-0.31	10	10
HMOX1	-0.12	0.35	-9999	-0.78	35	35
BHLHE40	-0.12	0.35	-9999	-0.76	36	36
BHLHE41	-0.12	0.36	-9999	-0.79	37	37
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.03	0.092	-9999	-0.26	2	2
ENG	0.023	0.079	-9999	-10000	0	0
JUN	0.013	0.017	-9999	-0.25	1	1
RORA	-0.12	0.35	-9999	-0.78	34	34
ABCB1	-0.089	0.25	-9999	-1.2	12	12
TFRC	-0.12	0.35	-9999	-0.77	34	34
CXCR4	-0.12	0.36	-9999	-0.78	36	36
TF	-0.18	0.39	-9999	-0.78	52	52
CITED2	-0.12	0.35	-9999	-0.77	34	34
HIF1A/ARNT	-0.098	0.43	-9999	-0.9	30	30
LDHA	-0.025	0.083	-9999	-1.2	1	1
ETS1	-0.12	0.35	-9999	-0.77	34	34
PGK1	-0.12	0.35	-9999	-0.77	34	34
NOS2	-0.13	0.36	-9999	-0.78	38	38
ITGB2	-0.12	0.36	-9999	-0.78	39	39
ALDOA	-0.12	0.35	-9999	-0.77	34	34
Cbp/p300/CITED2	-0.12	0.37	-9999	-0.87	28	28
FOS	0.006	0.045	-9999	-0.25	8	8
HK2	-0.12	0.35	-9999	-0.78	34	34
SP1	0.017	0.017	-9999	-10000	0	0
GCK	-0.065	0.3	-9999	-1.3	12	12
HK1	-0.12	0.35	-9999	-0.77	34	34
NPM1	-0.12	0.35	-9999	-0.77	34	34
EGLN1	-0.12	0.35	-9999	-0.76	35	35
CREB1	0.02	0.001	-9999	-10000	0	0
PGM1	-0.12	0.35	-9999	-0.81	30	30
SMAD3	0.011	0.037	-9999	-0.42	2	2
EDN1	-0.03	0.23	-9999	-0.79	15	15
IGFBP1	-0.13	0.35	-9999	-0.77	34	34
VEGFA	-0.063	0.28	-9999	-0.66	21	21
HIF1A/JAB1	0.006	0.042	-9999	-10000	0	0
CP	-0.16	0.38	-9999	-0.79	46	46
CXCL12	-0.13	0.37	-9999	-0.78	42	42
COPS5	0.014	0.002	-9999	-10000	0	0
SMAD3/SMAD4	0.02	0.027	-9999	-0.29	2	2
BNIP3	-0.12	0.35	-9999	-0.76	35	35
EGLN3	-0.12	0.36	-9999	-0.78	36	36
CA9	-0.15	0.37	-9999	-0.78	43	43
TERT	-0.14	0.37	-9999	-0.8	39	39
ENO1	-0.12	0.35	-9999	-0.77	34	34
PFKL	-0.12	0.35	-9999	-0.77	34	34
NCOA1	0.014	0.001	-9999	-10000	0	0
ADM	-0.12	0.36	-9999	-0.78	39	39
ARNT	-0.008	0.063	-9999	-10000	0	0
HNF4A	-0.008	0.055	-9999	-0.26	10	10
ADFP	-0.13	0.34	-9999	-0.73	40	40
SLC2A1	-0.059	0.27	-9999	-0.64	20	20
LEP	-0.13	0.35	-9999	-0.76	37	37
HIF1A/ARNT/Cbp/p300	-0.082	0.32	-9999	-0.73	24	24
EPO	-0.045	0.24	-9999	-0.61	13	13
CREBBP	-0.013	0.11	-9999	-0.29	13	13
HIF1A/ARNT/Cbp/p300/HDAC7	-0.068	0.32	-9999	-0.74	21	21
PFKFB3	-0.12	0.35	-9999	-0.76	35	35
NT5E	-0.14	0.38	-9999	-0.79	41	41

×

Calcium signaling in the CD4+ TCR 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.012	0.056	-9999	-0.28	8	8
NFATC2	-0.03	0.085	-9999	-0.27	26	26
NFATC3	-0.004	0.031	-9999	-10000	0	0
CD40LG	-0.15	0.27	-9999	-0.53	69	69
PTGS2	-0.15	0.26	-9999	-0.51	72	72
JUNB	0.012	0.023	-9999	-0.25	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.003	0.02	-9999	-10000	0	0
CaM/Ca2+	-0.003	0.02	-9999	-10000	0	0
CALM1	0.007	0.011	-9999	-10000	0	0
JUN	0.006	0.02	-9999	-0.26	1	1
mol:Ca2+	-0.009	0.012	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.005	0.007	-9999	-10000	0	0
FOSL1	-0.051	0.14	-9999	-0.35	47	47
CREM	0.013	0.016	-9999	-0.25	1	1
Jun/NFAT1-c-4/p21SNFT	-0.075	0.16	-9999	-0.38	41	41
FOS	-0.001	0.047	-9999	-0.26	8	8
IFNG	-0.17	0.28	-9999	-0.54	80	80
AP-1/NFAT1-c-4	-0.15	0.28	-9999	-0.55	70	70
FASLG	-0.16	0.29	-9999	-0.59	66	66
NFAT1-c-4/ICER1	-0.044	0.12	-9999	-0.31	27	27
IL2RA	-0.15	0.27	-9999	-0.56	60	60
FKBP12/FK506	0.01	0	-9999	-10000	0	0
CSF2	-0.13	0.24	-9999	-0.5	60	60
JunB/Fra1/NFAT1-c-4	-0.065	0.13	-9999	-0.31	38	38
IL4	-0.13	0.24	-9999	-0.5	59	59
IL2	-0.007	0.025	-9999	-10000	0	0
IL3	-0.015	0.021	-9999	-10000	0	0
FKBP1A	0.014	0	-9999	-10000	0	0
BATF3	0.002	0.068	-9999	-0.38	8	8
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.014	0.002	-9999	-10000	0	0

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.032	0.13	-9999	-0.32	25	25
NF kappa B1 p50/RelA/I kappa B alpha	-0.012	0.12	-9999	-0.35	17	17
alphaV/beta3 Integrin/Osteopontin/Src	-0.028	0.11	-9999	-0.27	40	40
AP1	-0.032	0.16	-9999	-0.45	23	23
ILK	-0.042	0.13	-9999	-0.36	21	21
bone resorption	-0.034	0.14	-9999	-0.39	23	23
PTK2B	0.009	0.038	-9999	-0.29	4	4
PYK2/p130Cas	-0.036	0.14	-9999	-0.39	21	21
ITGAV	0.007	0.061	-9999	-0.39	6	6
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.009	0.059	-9999	-0.29	10	10
alphaV/beta3 Integrin/Osteopontin	-0.049	0.14	-9999	-0.28	65	65
MAP3K1	-0.048	0.14	-9999	-0.26	68	68
JUN	0.013	0.016	-9999	-0.25	1	1
MAPK3	-0.033	0.13	-9999	-0.35	20	20
MAPK1	-0.033	0.13	-9999	-0.35	20	20
Rac1/GDP	0.01	0	-9999	-10000	0	0
NFKB1	0.014	0	-9999	-10000	0	0
MAPK8	-0.043	0.14	-9999	-0.34	29	29
ITGB3	-0.056	0.16	-9999	-0.38	49	49
NFKBIA	-0.027	0.13	-9999	-0.36	20	20
FOS	0.006	0.045	-9999	-0.25	8	8
CD44	0.009	0.046	-9999	-0.42	3	3
CHUK	0.012	0.027	-9999	-0.42	1	1
PLAU	-0.037	0.2	-9999	-1	7	7
NF kappa B1 p50/RelA	-0.011	0.12	-9999	-0.35	18	18
BCAR1	0.01	0.037	-9999	-0.42	2	2
RELA	0.014	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.032	0.12	-9999	-0.27	52	52
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.054	0.15	-9999	-0.27	71	71
VAV3	-0.06	0.15	-9999	-0.33	41	41
MAP3K14	-0.041	0.13	-9999	-0.25	65	65
ROCK2	0.002	0.069	-9999	-0.42	7	7
SPP1	-0.05	0.15	-9999	-0.36	47	47
RAC1	0.014	0	-9999	-10000	0	0
Rac1/GTP	-0.049	0.14	-9999	-0.35	30	30
MMP2	-0.042	0.17	-9999	-0.45	28	28

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.034	0.18	-10000	0	-0.53	26	26
IHH	-0.002	0.055	-10000	0	-0.23	8	8
SHH Np/Cholesterol/GAS1	0.003	0.05	-10000	0	-0.22	10	10
LRPAP1	0.014	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	-0.003	0.05	0.22	10	-10000	0	10
SMO/beta Arrestin2	-0.032	0.15	-10000	0	-0.44	17	17
SMO	-0.04	0.15	-10000	0	-0.41	24	24
AKT1	-0.005	0.085	-10000	0	-0.32	5	5
ARRB2	0.014	0	-10000	0	-10000	0	0
BOC	-0.016	0.099	-10000	0	-0.32	24	24
ADRBK1	0.014	0	-10000	0	-10000	0	0
heart looping	-0.04	0.15	-10000	0	-0.4	24	24
STIL	-0.008	0.098	-10000	0	-0.34	12	12
DHH N/PTCH2	-0.021	0.091	-10000	0	-0.2	49	49
DHH N/PTCH1	-0.03	0.13	-10000	0	-0.32	31	31
PIK3CA	0.008	0.048	-10000	0	-0.38	4	4
DHH	-0.034	0.12	-10000	0	-0.29	41	41
PTHLH	-0.049	0.24	-10000	0	-0.78	22	22
determination of left/right symmetry	-0.04	0.15	-10000	0	-0.4	24	24
PIK3R1	0.01	0.037	-10000	0	-0.42	2	2
skeletal system development	-0.049	0.24	-10000	0	-0.77	22	22
IHH N/Hhip	-0.004	0.061	-10000	0	-0.2	19	19
DHH N/Hhip	-0.027	0.091	-10000	0	-0.2	55	55
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.04	0.15	-10000	0	-0.4	24	24
pancreas development	-0.008	0.065	-10000	0	-0.25	18	18
HHAT	0.005	0.059	-10000	0	-0.42	5	5
PI3K	0.014	0.048	-10000	0	-0.31	5	5
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	0.004	0.061	-10000	0	-0.39	6	6
somite specification	-0.04	0.15	-10000	0	-0.4	24	24
SHH Np/Cholesterol/PTCH1	-0.012	0.1	-10000	0	-0.28	24	24
SHH Np/Cholesterol/PTCH2	0.001	0.052	-10000	0	-0.22	10	10
SHH Np/Cholesterol/Megalin	-0.096	0.11	-10000	0	-0.24	78	78
SHH	-0.001	0.052	-10000	0	-0.2	15	15
catabolic process	-0.014	0.12	-10000	0	-0.37	22	22
SMO/Vitamin D3	-0.024	0.12	-10000	0	-0.35	23	23
SHH Np/Cholesterol/Hhip	-0.004	0.054	-10000	0	-0.24	8	8
LRP2	-0.19	0.18	-10000	0	-0.34	152	152
receptor-mediated endocytosis	-0.09	0.15	-10000	0	-0.38	38	38
SHH Np/Cholesterol/BOC	-0.008	0.066	-10000	0	-0.23	14	14
SHH Np/Cholesterol/CDO	0.004	0.051	-10000	0	-0.24	8	8
mesenchymal cell differentiation	0.004	0.053	0.24	8	-10000	0	8
mol:Vitamin D3	-0.009	0.1	-10000	0	-0.28	24	24
IHH N/PTCH2	0.003	0.062	-10000	0	-0.27	10	10
CDON	0.007	0.053	-10000	0	-0.42	4	4
IHH N/PTCH1	-0.011	0.12	-10000	0	-0.37	22	22
Megalin/LRPAP1	-0.12	0.13	-10000	0	-0.22	152	152
PTCH2	0.001	0.065	-10000	0	-0.32	10	10
SHH Np/Cholesterol	0.001	0.039	-10000	0	-0.22	5	5
PTCH1	-0.014	0.12	-10000	0	-0.37	22	22
HHIP	-0.008	0.065	-10000	0	-0.25	18	18

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.012	0.11	-9999	-0.45	16	16
Syndecan-4/Syndesmos	-0.039	0.16	-9999	-0.43	32	32
positive regulation of JNK cascade	-0.049	0.17	-9999	-0.45	33	33
Syndecan-4/ADAM12	-0.044	0.16	-9999	-0.44	33	33
CCL5	-0.06	0.16	-9999	-0.38	50	50
Rac1/GDP	0.01	0	-9999	-10000	0	0
DNM2	0.014	0	-9999	-10000	0	0
ITGA5	0.004	0.058	-9999	-0.31	8	8
SDCBP	0.009	0.041	-9999	-0.36	3	3
PLG	0.001	0.018	-9999	-0.25	1	1
ADAM12	0.002	0.068	-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	-0.006	0.016	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.081	0.18	-9999	-0.47	36	36
Syndecan-4/CXCL12/CXCR4	-0.051	0.18	-9999	-0.48	33	33
Syndecan-4/Laminin alpha3	-0.05	0.16	-9999	-0.44	34	34
MDK	-0.025	0.12	-9999	-0.36	27	27
Syndecan-4/FZD7	-0.046	0.16	-9999	-0.44	34	34
Syndecan-4/Midkine	-0.056	0.18	-9999	-0.45	37	37
FZD7	-0.003	0.076	-9999	-0.33	13	13
Syndecan-4/FGFR1/FGF	-0.077	0.18	-9999	-0.45	38	38
THBS1	-0.013	0.1	-9999	-0.37	19	19
integrin-mediated signaling pathway	-0.057	0.17	-9999	-0.45	38	38
positive regulation of MAPKKK cascade	-0.049	0.17	-9999	-0.45	33	33
Syndecan-4/TACI	-0.079	0.17	-9999	-0.46	36	36
CXCR4	-0.002	0.076	-9999	-0.36	11	11
cell adhesion	-0.004	0.081	-9999	-0.23	25	25
Syndecan-4/Dynamin	-0.039	0.16	-9999	-0.43	32	32
Syndecan-4/TSP1	-0.051	0.17	-9999	-0.45	35	35
Syndecan-4/GIPC	-0.039	0.16	-9999	-0.43	32	32
Syndecan-4/RANTES	-0.072	0.18	-9999	-0.49	34	34
ITGB1	0.013	0.016	-9999	-0.25	1	1
LAMA1	-0.08	0.17	-9999	-0.36	67	67
LAMA3	-0.012	0.089	-9999	-0.3	21	21
RAC1	0.014	0	-9999	-10000	0	0
PRKCA	0.001	0.086	-9999	-0.35	13	13
Syndecan-4/alpha-Actinin	-0.042	0.16	-9999	-0.44	32	32
TFPI	0	0.067	-9999	-0.31	11	11
F2	-0.001	0.024	-9999	-0.25	2	2
alpha5/beta1 Integrin	0.013	0.044	-9999	-0.23	8	8
positive regulation of cell adhesion	-0.084	0.18	-9999	-0.47	36	36
ACTN1	0.007	0.053	-9999	-0.42	4	4
TNC	-0.031	0.13	-9999	-0.41	28	28
Syndecan-4/CXCL12	-0.053	0.17	-9999	-0.47	33	33
FGF6	0	0.002	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
CXCL12	-0.018	0.11	-9999	-0.4	20	20
TNFRSF13B	-0.076	0.15	-9999	-0.33	68	68
FGF2	-0.079	0.18	-9999	-0.4	59	59
FGFR1	-0.002	0.07	-9999	-0.3	13	13
Syndecan-4/PI-4-5-P2	-0.047	0.15	-9999	-0.44	32	32
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.012	0.1	-9999	-0.39	18	18
cell migration	-0.002	0.007	-9999	-10000	0	0
PRKCD	0.014	0.025	-9999	-0.38	1	1
vasculogenesis	-0.049	0.16	-9999	-0.44	35	35
SDC4	-0.049	0.16	-9999	-0.46	32	32
Syndecan-4/Tenascin C	-0.059	0.18	-9999	-0.46	38	38
Syndecan-4/PI-4-5-P2/PKC alpha	-0.005	0.013	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.041	0.16	-9999	-0.43	32	32
MMP9	-0.061	0.15	-9999	-0.34	56	56
Rac1/GTP	-0.005	0.083	-9999	-0.24	25	25
cytoskeleton organization	-0.038	0.15	-9999	-0.42	32	32
GIPC1	0.014	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.045	0.16	-9999	-0.43	33	33

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	-0.015	0.11	-10000	0	-0.41	18	18
positive regulation of NF-kappaB transcription factor activity	-0.028	0.1	-10000	0	-0.22	53	53
MAP2K4	0.001	0.083	-10000	0	-0.28	12	12
IKBKB	0.014	0	-10000	0	-10000	0	0
TNFRSF10B	-0.012	0.1	-10000	0	-0.42	16	16
TNFRSF10A	-0.041	0.14	-10000	0	-0.37	38	38
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	-0.028	0.1	-10000	0	-0.28	38	38
TRAIL/TRAILR2	-0.019	0.1	-10000	0	-0.29	33	33
TRAIL/TRAILR3	-0.029	0.12	-10000	0	-0.28	43	43
TRAIL/TRAILR1	-0.037	0.13	-10000	0	-0.34	36	36
TRAIL/TRAILR4	-0.028	0.1	-10000	0	-0.22	53	53
TRAIL/TRAILR1/DAP3/GTP	-0.018	0.1	-10000	0	-0.25	36	36
IKK complex	0.012	0.05	-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	-0.002	0.076	-10000	0	-0.28	18	18
MAP3K1	-0.005	0.088	-10000	0	-0.26	22	22
TRAILR4 (trimer)	-0.028	0.1	-10000	0	-0.28	38	38
TRADD	0.014	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	-0.041	0.14	-10000	0	-0.36	38	38
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.008	0.097	-10000	0	-0.24	36	36
CFLAR	0.012	0.027	-10000	0	-0.42	1	1
MAPK1	-0.002	0.076	-10000	0	-0.28	18	18
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.003	0.099	-10000	0	-0.23	36	36
mol:ceramide	-0.007	0.069	-10000	0	-0.18	32	32
FADD	0.013	0.016	-10000	0	-0.25	1	1
MAPK8	0.003	0.085	-10000	0	-0.29	11	11
TRAF2	0.014	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	-0.029	0.12	-10000	0	-0.36	30	30
CHUK	0.012	0.027	-10000	0	-0.42	1	1
TRAIL/TRAILR1/FADD	-0.022	0.11	-10000	0	-0.28	36	36
DAP3	0.014	0	-10000	0	-10000	0	0
CASP10	-0.019	0.13	0.22	3	-0.35	24	27
JNK cascade	-0.028	0.1	-10000	0	-0.22	53	53
TRAIL (trimer)	-0.015	0.11	-10000	0	-0.41	18	18
TNFRSF10C	-0.029	0.12	-10000	0	-0.36	30	30
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.01	0.098	-10000	0	-0.23	36	36
TRAIL/TRAILR2/FADD	-0.006	0.09	-10000	0	-0.24	32	32
cell death	-0.007	0.069	-10000	0	-0.18	32	32
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.003	0.077	-10000	0	-0.2	32	32
TRAILR2 (trimer)	-0.012	0.1	-10000	0	-0.42	16	16
CASP8	0.002	0.063	-10000	0	-0.95	1	1
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.011	0.078	-10000	0	-0.2	32	32

×

JNK signaling in the CD4+ TCR pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.027	0.14	-9999	-0.32	42	42
MAP4K1	-0.021	0.11	-9999	-0.37	24	24
MAP3K8	0	0.07	-9999	-0.33	11	11
PRKCB	-0.044	0.14	-9999	-0.35	42	42
DBNL	0.014	0	-9999	-10000	0	0
CRKL	0.013	0.016	-9999	-0.25	1	1
MAP3K1	-0.02	0.13	-9999	-0.44	19	19
JUN	-0.05	0.22	-9999	-0.7	27	27
MAP3K7	-0.016	0.13	-9999	-0.45	17	17
GRAP2	-0.012	0.1	-9999	-0.39	17	17
CRK	0.014	0	-9999	-10000	0	0
MAP2K4	-0.016	0.14	-9999	-0.46	19	19
LAT	-0.019	0.11	-9999	-0.34	25	25
LCP2	-0.011	0.1	-9999	-0.42	15	15
MAPK8	-0.058	0.23	-9999	-0.74	27	27
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.021	0.14	-9999	-0.48	17	17
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.019	0.13	-9999	-0.29	42	42

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.013	0.046	-9999	-0.29	6	6
VLDLR	-0.005	0.088	-9999	-0.41	12	12
CRKL	0.013	0.016	-9999	-0.25	1	1
LRPAP1	0.014	0	-9999	-10000	0	0
FYN	0.014	0	-9999	-10000	0	0
ITGA3	-0.024	0.12	-9999	-0.37	26	26
RELN/VLDLR/Fyn	-0.041	0.11	-9999	-0.27	35	35
MAPK8IP1/MKK7/MAP3K11/JNK1	0.024	0.059	-9999	-0.19	19	19
AKT1	-0.029	0.096	-9999	-0.23	38	38
MAP2K7	0.014	0	-9999	-10000	0	0
RAPGEF1	0.014	0	-9999	-10000	0	0
DAB1	-0.02	0.078	-9999	-0.25	28	28
RELN/LRP8/DAB1	-0.044	0.092	-9999	-0.22	40	40
LRPAP1/LRP8	0.02	0	-9999	-10000	0	0
RELN/LRP8/DAB1/Fyn	-0.034	0.087	-9999	-0.2	40	40
DAB1/alpha3/beta1 Integrin	-0.066	0.1	-9999	-0.28	33	33
long-term memory	-0.046	0.1	-9999	-0.22	56	56
DAB1/LIS1	-0.031	0.097	-9999	-0.21	47	47
DAB1/CRLK/C3G	-0.05	0.078	-9999	-0.31	9	9
PIK3CA	0.008	0.048	-9999	-0.38	4	4
DAB1/NCK2	-0.031	0.098	-9999	-0.21	47	47
ARHGEF2	0.014	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.022	0.096	-9999	-0.28	32	32
CDK5R1	0.004	0.064	-9999	-0.42	6	6
RELN	-0.086	0.15	-9999	-0.31	82	82
PIK3R1	0.01	0.037	-9999	-0.42	2	2
RELN/LRP8/Fyn	-0.031	0.092	-9999	-0.24	28	28
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.044	0.1	-9999	-0.22	50	50
MAPK8	0.009	0.046	-9999	-0.42	3	3
RELN/VLDLR/DAB1	-0.053	0.11	-9999	-0.25	47	47
ITGB1	0.013	0.016	-9999	-0.25	1	1
MAP1B	-0.049	0.11	-9999	-0.23	55	55
RELN/LRP8	-0.031	0.092	-9999	-0.24	28	28
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.037	0.096	-9999	-0.21	47	47
PI3K	0.014	0.048	-9999	-0.31	5	5
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.007	0.084	-9999	-0.25	27	27
RAP1A	-0.023	0.089	-9999	-0.29	9	9
PAFAH1B1	0.014	0	-9999	-10000	0	0
MAPK8IP1	-0.012	0.1	-9999	-0.41	16	16
CRLK/C3G	0.02	0.011	-9999	-10000	0	0
GRIN2B	-0.008	0.063	-9999	-0.25	17	17
NCK2	0.014	0	-9999	-10000	0	0
neuron differentiation	-0.012	0.076	-9999	-0.26	8	8
neuron adhesion	-0.029	0.1	-9999	-0.28	22	22
LRP8	0.014	0	-9999	-10000	0	0
GSK3B	-0.023	0.092	-9999	-0.33	10	10
RELN/VLDLR/DAB1/Fyn	-0.043	0.1	-9999	-0.23	47	47
MAP3K11	0.012	0.027	-9999	-0.42	1	1
RELN/VLDLR/DAB1/P13K	-0.036	0.1	-9999	-0.25	38	38
CDK5	0.014	0	-9999	-10000	0	0
MAPT	-0.037	0.13	-9999	-0.34	38	38
neuron migration	-0.017	0.11	-9999	-0.28	31	31
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.012	0.077	-9999	-0.26	8	8
RELN/VLDLR	-0.029	0.1	-9999	-0.24	35	35

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.006	0.045	-10000	0	-0.25	8	8
EPHB2	-0.015	0.11	-10000	0	-0.4	18	18
EFNB1	0.006	0.054	-10000	0	-0.22	14	14
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.016	0.11	-10000	0	-0.24	41	41
Ephrin B2/EPHB1-2	-0.018	0.093	-10000	0	-0.25	29	29
neuron projection morphogenesis	-0.039	0.095	-10000	0	-0.23	41	41
Ephrin B1/EPHB1-2/Tiam1	-0.023	0.12	-10000	0	-0.25	43	43
DNM1	-0.002	0.074	-10000	0	-0.33	12	12
cell-cell signaling	0	0.002	-10000	0	-10000	0	0
MAP2K4	-0.019	0.13	-10000	0	-0.52	16	16
YES1	-0.036	0.19	-10000	0	-0.8	15	15
Ephrin B1/EPHB1-2/NCK2	-0.009	0.098	-10000	0	-0.24	30	30
PI3K	-0.017	0.14	-10000	0	-0.58	15	15
mol:GDP	-0.024	0.12	-10000	0	-0.25	43	43
ITGA2B	-0.025	0.11	-10000	0	-0.3	32	32
endothelial cell proliferation	0.004	0.055	-10000	0	-0.19	18	18
FYN	-0.034	0.18	-10000	0	-0.78	15	15
MAP3K7	-0.026	0.14	-10000	0	-0.56	16	16
FGR	-0.041	0.18	-10000	0	-0.77	15	15
TIAM1	-0.015	0.11	-10000	0	-0.41	18	18
PIK3R1	0.01	0.037	-10000	0	-0.42	2	2
RGS3	0.011	0.031	-10000	0	-0.33	2	2
cell adhesion	-0.056	0.16	-10000	0	-0.58	17	17
LYN	-0.036	0.18	-10000	0	-0.78	15	15
Ephrin B1/EPHB1-2/Src Family Kinases	-0.041	0.17	-10000	0	-0.72	15	15
Ephrin B1/EPHB1-2	-0.038	0.14	-10000	0	-0.63	15	15
SRC	-0.034	0.18	-10000	0	-0.77	15	15
ITGB3	-0.058	0.16	-10000	0	-0.38	49	49
EPHB1	-0.035	0.12	-10000	0	-0.3	41	41
EPHB4	-0.003	0.082	-10000	0	-0.42	10	10
RAC1	0.014	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.004	0.055	-10000	0	-0.19	18	18
alphaIIb/beta3 Integrin	-0.057	0.13	-10000	0	-0.25	76	76
BLK	-0.064	0.19	-10000	0	-0.8	15	15
HCK	-0.05	0.18	-10000	0	-0.77	15	15
regulation of stress fiber formation	0.009	0.097	0.24	30	-10000	0	30
MAPK8	-0.015	0.13	-10000	0	-0.52	15	15
Ephrin B1/EPHB1-2/RGS3	-0.01	0.1	-10000	0	-0.24	31	31
endothelial cell migration	-0.027	0.12	-10000	0	-0.38	24	24
NCK2	0.014	0	-10000	0	-10000	0	0
PTPN13	-0.015	0.13	-10000	0	-0.54	15	15
regulation of focal adhesion formation	0.009	0.097	0.24	30	-10000	0	30
chemotaxis	0.011	0.099	0.24	31	-10000	0	31
PIK3CA	0.008	0.048	-10000	0	-0.38	4	4
Rac1/GTP	-0.02	0.11	-10000	0	-0.23	41	41
angiogenesis	-0.038	0.14	-10000	0	-0.62	15	15
LCK	-0.06	0.19	-10000	0	-0.77	15	15

×

EPHB forward 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	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	-0.24	43	43
cell-cell adhesion	0.056	0.086	0.3	17	-10000	0	17
Ephrin B/EPHB2/RasGAP	-0.017	0.095	-10000	0	-0.2	50	50
ITSN1	0.014	0	-10000	0	-10000	0	0
PIK3CA	0.008	0.048	-10000	0	-0.38	4	4
SHC1	0.014	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.004	0.07	-10000	0	-0.21	27	27
Ephrin B1/EPHB1	-0.01	0.069	-10000	0	-0.16	43	43
HRAS/GDP	-0.045	0.083	-10000	0	-0.28	14	14
Ephrin B/EPHB1/GRB7	-0.037	0.11	-10000	0	-0.22	55	55
Endophilin/SYNJ1	-0.021	0.084	-10000	0	-0.18	48	48
KRAS	0.013	0.016	-10000	0	-0.25	1	1
Ephrin B/EPHB1/Src	-0.025	0.1	-10000	0	-0.21	49	49
endothelial cell migration	0.013	0.058	-10000	0	-0.21	14	14
GRB2	0.014	0	-10000	0	-10000	0	0
GRB7	-0.013	0.077	-10000	0	-0.26	24	24
PAK1	-0.024	0.094	-10000	0	-0.26	11	11
HRAS	0.014	0	-10000	0	-10000	0	0
RRAS	-0.022	0.086	-10000	0	-0.19	49	49
DNM1	-0.002	0.074	-10000	0	-0.33	12	12
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.03	0.092	-10000	0	-0.2	48	48
lamellipodium assembly	-0.056	0.086	-10000	0	-0.3	17	17
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.015	0.083	-10000	0	-0.23	15	15
PIK3R1	0.01	0.037	-10000	0	-0.42	2	2
EPHB2	-0.014	0.1	-10000	0	-0.4	18	18
EPHB3	-0.023	0.12	-10000	0	-0.38	25	25
EPHB1	-0.034	0.12	-10000	0	-0.3	41	41
EPHB4	-0.003	0.082	-10000	0	-0.42	10	10
mol:GDP	-0.027	0.1	-10000	0	-0.24	35	35
Ephrin B/EPHB2	-0.023	0.093	-10000	0	-0.2	48	48
Ephrin B/EPHB3	-0.027	0.1	-10000	0	-0.22	49	49
JNK cascade	-0.008	0.082	-10000	0	-0.22	27	27
Ephrin B/EPHB1	-0.032	0.1	-10000	0	-0.22	48	48
RAP1/GDP	-0.012	0.095	-10000	0	-0.26	12	12
EFNB2	0.006	0.045	-10000	0	-0.25	8	8
EFNB3	-0.057	0.15	-10000	0	-0.35	51	51
EFNB1	0.012	0.023	-10000	0	-0.25	2	2
Ephrin B2/EPHB1-2	-0.018	0.093	-10000	0	-0.24	29	29
RAP1B	0.013	0.016	-10000	0	-0.25	1	1
RAP1A	0.014	0	-10000	0	-10000	0	0
CDC42/GTP	-0.057	0.092	-10000	0	-0.33	12	12
Rap1/GTP	-0.05	0.078	-10000	0	-0.29	12	12
axon guidance	-0.023	0.097	-10000	0	-0.24	43	43
MAPK3	-0.003	0.075	-10000	0	-0.24	6	6
MAPK1	-0.003	0.075	-10000	0	-0.24	6	6
Rac1/GDP	-0.018	0.097	-10000	0	-0.28	12	12
actin cytoskeleton reorganization	-0.043	0.07	-10000	0	-0.25	16	16
CDC42/GDP	-0.018	0.097	-10000	0	-0.28	12	12
PI3K	0.015	0.059	-10000	0	-0.21	14	14
EFNA5	-0.028	0.12	-10000	0	-0.39	27	27
Ephrin B2/EPHB4	0.004	0.055	-10000	0	-0.19	18	18
Ephrin B/EPHB2/Intersectin/N-WASP	-0.017	0.089	-10000	0	-0.2	46	46
CDC42	0.014	0	-10000	0	-10000	0	0
RAS family/GTP	-0.048	0.076	-10000	0	-0.28	12	12
PTK2	0.01	0.021	-10000	0	-10000	0	0
MAP4K4	-0.008	0.083	-10000	0	-0.22	27	27
SRC	0.012	0.027	-10000	0	-0.42	1	1
KALRN	-0.001	0.068	-10000	0	-0.3	12	12
Intersectin/N-WASP	0.02	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.019	0.1	-10000	0	-0.28	18	18
MAP2K1	-0.009	0.078	-10000	0	-0.26	6	6
WASL	0.014	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.007	0.091	-10000	0	-0.24	26	26
cell migration	-0.009	0.092	-10000	0	-0.27	8	8
NRAS	0.014	0	-10000	0	-10000	0	0
SYNJ1	-0.021	0.085	-10000	0	-0.19	48	48
PXN	0.014	0	-10000	0	-10000	0	0
TF	-0.091	0.12	-10000	0	-0.23	77	77
HRAS/GTP	-0.032	0.099	-10000	0	-0.31	12	12
Ephrin B1/EPHB1-2	-0.015	0.09	-10000	0	-0.25	26	26
cell adhesion mediated by integrin	0.037	0.075	0.2	36	-10000	0	36
RAC1	0.014	0	-10000	0	-10000	0	0
mol:GTP	-0.034	0.11	-10000	0	-0.27	20	20
RAC1-CDC42/GTP	-0.062	0.096	-10000	0	-0.32	20	20
RASA1	0.01	0.037	-10000	0	-0.42	2	2
RAC1-CDC42/GDP	-0.012	0.095	-10000	0	-0.27	11	11
ruffle organization	-0.028	0.1	-10000	0	-0.3	17	17
NCK1	0.014	0	-10000	0	-10000	0	0
receptor internalization	-0.023	0.091	-10000	0	-0.19	51	51
Ephrin B/EPHB2/KALRN	-0.022	0.1	-10000	0	-0.21	53	53
ROCK1	-0.004	0.069	-10000	0	-0.21	24	24
RAS family/GDP	-0.043	0.072	-10000	0	-0.25	15	15
Rac1/GTP	-0.059	0.09	-10000	0	-0.31	17	17
Ephrin B/EPHB1/Src/Paxillin	-0.021	0.091	-10000	0	-0.21	42	42

×

amb2 Integrin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.021	0.13	-9999	-0.36	28	28
alphaM/beta2 Integrin/GPIbA	-0.031	0.12	-9999	-0.33	28	28
alphaM/beta2 Integrin/proMMP-9	-0.043	0.15	-9999	-0.34	41	41
PLAUR	-0.002	0.073	-9999	-0.31	13	13
HMGB1	0.01	0.014	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	0.001	0.1	-9999	-0.38	15	15
AGER	0.006	0.035	-9999	-0.26	4	4
RAP1A	0.014	0	-9999	-10000	0	0
SELPLG	-0.004	0.084	-9999	-0.4	11	11
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.003	0.12	-9999	-0.36	19	19
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.062	0.15	-9999	-0.35	56	56
CYR61	0.001	0.063	-9999	-0.3	11	11
TLN1	0.014	0	-9999	-10000	0	0
Rap1/GTP	-0.044	0.11	-9999	-0.36	17	17
RHOA	0.014	0	-9999	-10000	0	0
P-selectin oligomer	-0.066	0.16	-9999	-0.36	57	57
MYH2	-0.043	0.12	-9999	-0.32	23	23
MST1R	-0.052	0.14	-9999	-0.31	54	54
leukocyte activation during inflammatory response	-0.011	0.091	-9999	-0.33	16	16
APOB	-0.006	0.053	-9999	-0.25	12	12
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.025	0.12	-9999	-0.34	29	29
JAM3	-0.013	0.1	-9999	-0.41	17	17
GP1BA	-0.041	0.12	-9999	-0.3	47	47
alphaM/beta2 Integrin/CTGF	-0.014	0.12	-9999	-0.38	21	21
alphaM/beta2 Integrin	-0.045	0.13	-9999	-0.35	25	25
JAM3 homodimer	-0.013	0.1	-9999	-0.41	17	17
ICAM2	0.009	0.041	-9999	-0.36	3	3
ICAM1	0.001	0.074	-9999	-0.42	8	8
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.045	0.13	-9999	-0.34	25	25
cell adhesion	-0.031	0.12	-9999	-0.32	28	28
NFKB1	-0.014	0.15	-9999	-0.39	28	28
THY1	0.007	0.046	-9999	-0.32	5	5
RhoA/GDP	0.01	0	-9999	-10000	0	0
Lipoprotein(a)	-0.003	0.034	-9999	-0.14	13	13
alphaM/beta2 Integrin/LRP/tPA	0.001	0.11	-9999	-0.32	22	22
IL6	-0.024	0.18	-9999	-0.44	30	30
ITGB2	-0.014	0.099	-9999	-0.41	15	15
elevation of cytosolic calcium ion concentration	-0.007	0.12	-9999	-0.38	23	23
alphaM/beta2 Integrin/JAM2/JAM3	-0.009	0.12	-9999	-0.32	29	29
JAM2	0.005	0.051	-9999	-0.3	7	7
alphaM/beta2 Integrin/ICAM1	-0.026	0.13	-9999	-0.3	38	38
alphaM/beta2 Integrin/uPA/Plg	-0.006	0.11	-9999	-0.42	16	16
RhoA/GTP	-0.046	0.12	-9999	-0.28	39	39
positive regulation of phagocytosis	-0.032	0.16	-9999	-0.6	15	15
Ron/MSP	-0.029	0.1	-9999	-0.22	56	56
alphaM/beta2 Integrin/uPAR/uPA	-0.006	0.12	-9999	-0.38	23	23
alphaM/beta2 Integrin/uPAR	-0.008	0.11	-9999	-0.35	21	21
PLAU	-0.003	0.076	-9999	-0.33	13	13
PLAT	-0.004	0.081	-9999	-0.35	13	13
actin filament polymerization	-0.041	0.12	-9999	-0.31	23	23
MST1	0.007	0.053	-9999	-0.42	4	4
alphaM/beta2 Integrin/lipoprotein(a)	-0.01	0.093	-9999	-0.33	16	16
TNF	-0.031	0.2	-9999	-0.53	29	29
RAP1B	0.013	0.016	-9999	-0.25	1	1
alphaM/beta2 Integrin/uPA	-0.008	0.12	-9999	-0.44	17	17
fibrinolysis	-0.007	0.11	-9999	-0.42	16	16
HCK	-0.011	0.1	-9999	-0.42	15	15
dendritic cell antigen processing and presentation	-0.045	0.13	-9999	-0.34	25	25
VTN	-0.029	0.1	-9999	-0.27	39	39
alphaM/beta2 Integrin/CYR61	-0.007	0.11	-9999	-0.38	17	17
LPA	-0.002	0.027	-9999	-0.25	3	3
LRP1	0.014	0	-9999	-10000	0	0
cell migration	-0.052	0.16	-9999	-0.36	46	46
FN1	-0.014	0.1	-9999	-0.4	18	18
alphaM/beta2 Integrin/Thy1	-0.003	0.1	-9999	-0.36	18	18
MPO	-0.01	0.091	-9999	-0.35	17	17
KNG1	0.002	0.023	-9999	-0.25	2	2
RAP1/GDP	0.018	0.009	-9999	-0.13	1	1
ROCK1	-0.042	0.12	-9999	-0.33	21	21
ELA2	0	0	-9999	-10000	0	0
PLG	0	0.016	-9999	-0.25	1	1
CTGF	-0.012	0.092	-9999	-0.32	20	20
alphaM/beta2 Integrin/Hck	-0.012	0.14	-9999	-0.51	18	18
ITGAM	-0.006	0.083	-9999	-0.42	10	10
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.041	0.16	-9999	-0.32	48	48
HP	-0.068	0.14	-9999	-0.31	65	65
leukocyte adhesion	-0.011	0.13	-9999	-0.41	19	19
SELP	-0.066	0.16	-9999	-0.36	57	57

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	0.015	0.11	0.39	19	-10000	0	19
PI3K Class IB/PDE3B	-0.015	0.11	-10000	0	-0.39	19	19
PDE3B	-0.015	0.11	-10000	0	-0.39	19	19

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.005	0.056	-9999	-0.22	15	15
ARNO/beta Arrestin1-2	0.016	0.035	-9999	-10000	0	0
EGFR	-0.021	0.1	-9999	-0.29	30	30
EPHA2	-0.001	0.073	-9999	-0.34	11	11
USP6	0.014	0	-9999	-10000	0	0
IQSEC1	0.014	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.074	0.14	-9999	-0.26	90	90
ARRB2	0.008	0.006	-9999	-10000	0	0
mol:GTP	-0.011	0.057	-9999	-0.17	20	20
ARRB1	0.01	0.037	-9999	-0.42	2	2
FBXO8	0.014	0	-9999	-10000	0	0
TSHR	-0.031	0.12	-9999	-0.33	34	34
EGF	-0.088	0.17	-9999	-0.37	71	71
somatostatin receptor activity	0	0	-9999	0	23	23
ARAP2	-0.022	0.12	-9999	-0.42	22	22
mol:GDP	-0.025	0.067	-9999	-0.2	19	19
mol:PI-3-4-5-P3	0	0	-9999	-0.001	12	12
ITGA2B	-0.025	0.11	-9999	-0.3	32	32
ARF6	0.014	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.027	0.04	-9999	-0.21	6	6
ADAP1	-0.009	0.094	-9999	-0.39	15	15
KIF13B	0.014	0	-9999	-10000	0	0
HGF/MET	-0.044	0.12	-9999	-0.29	39	39
PXN	0.014	0	-9999	-10000	0	0
ARF6/GTP	-0.035	0.075	-9999	-0.21	20	20
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.053	0.12	-9999	-0.26	58	58
ADRB2	-0.001	0.071	-9999	-0.32	12	12
receptor agonist activity	0	0	-9999	0	24	24
actin filament binding	0	0	-9999	0	24	24
SRC	0.012	0.027	-9999	-0.42	1	1
ITGB3	-0.059	0.16	-9999	-0.38	49	49
GNAQ	0.013	0	-9999	-10000	0	0
EFA6/PI-4-5-P2	0	0	-9999	-0.001	22	22
ARF6/GDP	-0.028	0.12	-9999	-0.31	36	36
ARF6/GDP/GULP/ACAP1	-0.045	0.12	-9999	-0.28	37	37
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.025	0.1	-9999	-0.22	49	49
ACAP1	-0.057	0.15	-9999	-0.35	51	51
ACAP2	0.012	0.027	-9999	-0.42	1	1
LHCGR/beta Arrestin2	0.002	0.009	-9999	-10000	0	0
EFNA1	0.014	0	-9999	-10000	0	0
HGF	-0.023	0.11	-9999	-0.32	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	21	21
endosomal lumen acidification	0	0	-9999	0	25	25
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.012	0.1	-9999	-0.41	16	16
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	19	19
MET	-0.041	0.14	-9999	-0.37	38	38
GNA14	-0.028	0.1	-9999	-0.27	39	39
GNA15	-0.003	0.081	-9999	-0.39	11	11
GIT1	0.014	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	22	22
GNA11	0.014	0	-9999	-10000	0	0
LHCGR	0.001	0.016	-9999	-0.25	1	1
AGTR1	-0.042	0.13	-9999	-0.35	40	40
desensitization of G-protein coupled receptor protein signaling pathway	0.002	0.009	-9999	-10000	0	0
IPCEF1/ARNO	-0.037	0.092	-9999	-0.36	2	2
alphaIIb/beta3 Integrin	-0.057	0.13	-9999	-0.25	76	76

×

Signaling events mediated by PTP1B

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
PDGFRB	0.01	0.037	-10000	0	-0.42	2	2
Jak2/Leptin Receptor	-0.039	0.14	0.19	1	-0.43	19	20
PTP1B/AKT1	-0.02	0.082	-10000	0	-0.24	21	21
FYN	0.014	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.029	0.09	-10000	0	-0.26	24	24
EGFR	-0.024	0.1	-10000	0	-0.3	30	30
EGF/EGFR	-0.066	0.13	-10000	0	-0.27	64	64
CSF1	0.002	0.069	-10000	0	-0.42	7	7
AKT1	0.014	0.001	-10000	0	-10000	0	0
INSR	0.012	0.027	-10000	0	-0.42	1	1
PTP1B/N-cadherin	-0.075	0.12	-10000	0	-0.26	57	57
Insulin Receptor/Insulin	-0.011	0.068	-10000	0	-0.25	8	8
HCK	-0.011	0.1	-10000	0	-0.42	15	15
CRK	0.014	0	-10000	0	-10000	0	0
TYK2	-0.023	0.086	-10000	0	-0.26	21	21
EGF	-0.09	0.18	-10000	0	-0.37	71	71
YES1	0.007	0.053	-10000	0	-0.42	4	4
CAV1	-0.033	0.1	-10000	0	-0.3	20	20
TXN	0.012	0.003	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.024	0.097	-10000	0	-0.25	27	27
cell migration	0.029	0.09	0.26	24	-10000	0	24
STAT3	0.013	0.001	-10000	0	-10000	0	0
PRLR	-0.068	0.15	-10000	0	-0.31	66	66
ITGA2B	-0.026	0.11	-10000	0	-0.3	32	32
CSF1R	-0.007	0.091	-10000	0	-0.41	13	13
Prolactin Receptor/Prolactin	-0.053	0.11	-10000	0	-0.3	29	29
FGR	-0.008	0.091	-10000	0	-0.37	15	15
PTP1B/p130 Cas	-0.023	0.088	-10000	0	-0.25	23	23
Crk/p130 Cas	-0.015	0.086	-10000	0	-0.24	21	21
DOK1	-0.015	0.083	-10000	0	-0.23	22	22
JAK2	-0.042	0.14	-10000	0	-0.43	19	19
Jak2/Leptin Receptor/Leptin	-0.037	0.12	-10000	0	-0.4	18	18
PIK3R1	0.01	0.037	-10000	0	-0.42	2	2
PTPN1	-0.029	0.09	-10000	0	-0.26	24	24
LYN	0.009	0.046	-10000	0	-0.42	3	3
CDH2	-0.1	0.18	-10000	0	-0.37	79	79
SRC	0.002	0.05	-10000	0	-0.57	1	1
ITGB3	-0.059	0.16	-10000	0	-0.38	49	49
CAT1/PTP1B	-0.066	0.16	-10000	0	-0.4	35	35
CAPN1	0.012	0.027	-10000	0	-0.43	1	1
CSK	0.014	0	-10000	0	-10000	0	0
PI3K	-0.021	0.069	-10000	0	-0.29	9	9
mol:H2O2	-0.001	0.003	-10000	0	-10000	0	0
STAT3 (dimer)	-0.028	0.12	-10000	0	-0.41	16	16
negative regulation of transcription	-0.042	0.14	-10000	0	-0.42	19	19
FCGR2A	0.004	0.063	-10000	0	-0.37	7	7
FER	0.006	0.054	-10000	0	-0.43	4	4
alphaIIb/beta3 Integrin	-0.058	0.13	-10000	0	-0.25	76	76
BLK	-0.082	0.16	-10000	0	-0.33	74	74
Insulin Receptor/Insulin/Shc	0.018	0.016	-10000	0	-0.24	1	1
RHOA	0.014	0.001	-10000	0	-10000	0	0
LEPR	0.004	0.062	-10000	0	-0.37	7	7
BCAR1	0.01	0.037	-10000	0	-0.42	2	2
p210 bcr-abl/Grb2	0.014	0	-10000	0	-10000	0	0
mol:NADPH	-0.001	0.003	-10000	0	-10000	0	0
TRPV6	-0.071	0.19	-10000	0	-0.48	36	36
PRL	-0.012	0.066	-10000	0	-0.25	19	19
SOCS3	-0.023	0.22	-10000	0	-1.2	8	8
SPRY2	0.007	0.049	-10000	0	-0.38	4	4
Insulin Receptor/Insulin/IRS1	0.004	0.059	-10000	0	-0.24	14	14
CSF1/CSF1R	-0.028	0.12	-10000	0	-0.29	30	30
Ras protein signal transduction	0.019	0.027	-10000	0	-10000	0	0
IRS1	-0.009	0.095	-10000	0	-0.41	14	14
INS	0	0.002	-10000	0	-10000	0	0
LEP	-0.019	0.083	-10000	0	-0.25	29	29
STAT5B	-0.031	0.095	-10000	0	-0.26	26	26
STAT5A	-0.032	0.095	-10000	0	-0.26	26	26
GRB2	0.014	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.023	0.091	-10000	0	-0.26	22	22
CSN2	-0.014	0.051	-10000	0	-10000	0	0
PIK3CA	0.008	0.048	-10000	0	-0.38	4	4
LAT	-0.03	0.12	-10000	0	-0.46	18	18
YBX1	0.02	0.009	-10000	0	-10000	0	0
LCK	-0.067	0.16	-10000	0	-0.37	56	56
SHC1	0.014	0	-10000	0	-10000	0	0
NOX4	-0.048	0.14	-10000	0	-0.38	41	41

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.004	0.14	-10000	0	-1.1	4	4
VDR	0.004	0.064	-10000	0	-0.42	6	6
FAM120B	0.014	0	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.026	0.13	-10000	0	-0.31	23	23
RXRs/LXRs/DNA/Oxysterols	-0.026	0.15	-10000	0	-0.43	23	23
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	-0.008	0.089	-10000	0	-0.23	31	31
RXRs/NUR77	-0.019	0.11	-10000	0	-0.21	60	60
RXRs/PPAR	-0.021	0.098	-10000	0	-0.19	62	62
NCOR2	0.014	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.003	0.045	-10000	0	-0.3	6	6
RARs/VDR/DNA/Vit D3	0.009	0.073	-10000	0	-0.21	24	24
RARA	0.014	0	-10000	0	-10000	0	0
NCOA1	0.014	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.004	0.064	-10000	0	-0.42	6	6
RARs/RARs/DNA/9cRA	0.007	0.062	-10000	0	-0.2	20	20
RARG	0.014	0	-10000	0	-10000	0	0
RPS6KB1	0.013	0.059	-10000	0	-0.4	4	4
RARs/THRs/DNA/SMRT	-0.008	0.089	-10000	0	-0.23	31	31
THRA	0.014	0	-10000	0	-10000	0	0
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.003	0.045	-10000	0	-0.3	6	6
RXRs/PPAR/9cRA/PGJ2/DNA	-0.024	0.11	0.28	1	-0.21	60	61
NR1H4	-0.005	0.051	-10000	0	-0.25	11	11
RXRs/LXRs/DNA	-0.008	0.12	-10000	0	-0.31	11	11
NR1H2	0.013	0.031	-10000	0	-0.44	1	1
NR1H3	0.013	0.032	-10000	0	-0.46	1	1
RXRs/VDR/DNA/Vit D3	-0.021	0.1	-10000	0	-0.2	63	63
NR4A1	0.008	0.048	-10000	0	-0.38	4	4
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.025	0.089	-10000	0	-0.18	59	59
RXRG	-0.084	0.18	-10000	0	-0.41	61	61
RXR alpha/CCPG	0.021	0.009	-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	-0.044	0.13	-10000	0	-0.3	48	48
PPARG	0.007	0.051	-10000	0	-0.35	5	5
PPARD	0.014	0	-10000	0	-10000	0	0
TNF	-0.055	0.26	-10000	0	-0.86	20	20
mol:Oxysterols	0.001	0.013	-10000	0	-10000	0	0
cholesterol transport	-0.026	0.15	-10000	0	-0.43	23	23
PPARA	0.014	0	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	-0.022	0.12	-10000	0	-0.4	23	23
RXRs/NUR77/BCL2	-0.034	0.11	-10000	0	-0.22	66	66
SREBF1	-0.019	0.15	-10000	0	-0.44	20	20
RXRs/RXRs/DNA/9cRA	-0.023	0.11	0.27	1	-0.21	60	61
ABCA1	-0.028	0.19	-10000	0	-0.75	11	11
RARs/THRs	-0.007	0.095	-10000	0	-0.23	31	31
RXRs/FXR	-0.026	0.11	-10000	0	-0.22	59	59
BCL2	0.001	0.074	-10000	0	-0.42	8	8

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.029	0.2	-9999	-0.56	27	27
MAP3K8	0	0.07	-9999	-0.33	11	11
FOS	-0.04	0.2	-9999	-0.57	28	28
PRKCA	-0.005	0.086	-9999	-0.38	13	13
PTPN7	-0.035	0.13	-9999	-0.37	34	34
HRAS	0.014	0	-9999	-10000	0	0
PRKCB	-0.043	0.14	-9999	-0.35	42	42
NRAS	0.014	0	-9999	-10000	0	0
RAS family/GTP	0.027	0.009	-9999	-10000	0	0
MAPK3	-0.042	0.2	-9999	-0.59	26	26
MAP2K1	-0.026	0.15	-9999	-0.4	33	33
ELK1	0.014	0.001	-9999	-10000	0	0
BRAF	-0.03	0.14	-9999	-0.38	35	35
mol:GTP	0	0	-9999	-0.002	7	7
MAPK1	-0.042	0.2	-9999	-0.59	26	26
RAF1	-0.027	0.14	-9999	-0.38	33	33
KRAS	0.013	0.016	-9999	-0.25	1	1

×

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

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
BAG4	0.005	0.059	-9999	-0.42	5	5
Caspase 8 (4 units)	-0.011	0.096	-9999	-0.34	8	8
NEF	-0.023	0.052	-9999	-0.16	21	21
NFKBIA	0	0.035	-9999	-10000	0	0
BIRC3	-0.042	0.17	-9999	-0.37	51	51
CYCS	-0.017	0.1	-9999	-0.23	46	46
RIPK1	0.014	0	-9999	-10000	0	0
CD247	-0.079	0.18	-9999	-0.35	67	67
MAP2K7	-0.009	0.096	-9999	-0.31	11	11
protein ubiquitination	0.014	0.076	-9999	-0.28	9	9
CRADD	0.013	0.016	-9999	-0.25	1	1
DAXX	0.014	0	-9999	-10000	0	0
FAS	0.007	0.053	-9999	-0.42	4	4
BID	-0.023	0.11	-9999	-0.24	46	46
NF-kappa-B/RelA/I kappa B alpha	-0.007	0.094	-9999	-0.23	33	33
TRADD	0.014	0	-9999	-10000	0	0
MAP3K5	0.008	0.044	-9999	-0.33	4	4
CFLAR	0.012	0.027	-9999	-0.42	1	1
FADD	0.013	0.016	-9999	-0.25	1	1
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.007	0.094	-9999	-0.23	33	33
MAPK8	-0.006	0.093	-9999	-0.3	9	9
APAF1	0.007	0.053	-9999	-0.42	4	4
TRAF1	-0.019	0.098	-9999	-0.29	29	29
TRAF2	0.014	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.029	0.11	-9999	-0.26	46	46
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.004	0.092	-9999	-0.34	11	11
CHUK	0.013	0.081	-9999	-0.3	9	9
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.033	0.039	-9999	-0.19	7	7
TCRz/NEF	-0.08	0.18	-9999	-0.32	77	77
TNF	-0.025	0.11	-9999	-0.34	29	29
FASLG	-0.11	0.24	-9999	-0.49	68	68
NFKB1	0	0.035	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	0	0.075	-9999	-0.24	20	20
CASP6	0.005	0.085	-9999	-0.42	4	4
CASP7	-0.039	0.19	-9999	-0.48	36	36
RELA	0	0.035	-9999	-10000	0	0
CASP2	0.012	0.027	-9999	-0.42	1	1
CASP3	-0.039	0.19	-9999	-0.48	35	35
TNFRSF1A	0.014	0	-9999	-10000	0	0
TNFR1A/BAG4	0.014	0.042	-9999	-0.29	5	5
CASP8	0.012	0.027	-9999	-0.42	1	1
CASP9	0.014	0	-9999	-10000	0	0
MAP3K14	0.009	0.086	-9999	-0.31	11	11
APAF-1/Caspase 9	-0.072	0.13	-9999	-0.34	40	40
BCL2	-0.006	0.095	-9999	-0.29	12	12

×

Effects of Botulinum toxin

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0	0.042	-9999	-0.17	14	14
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	0.006	0.04	-9999	-0.17	13	13
STXBP1	0.014	0	-9999	-10000	0	0
ACh/CHRNA1	-0.058	0.1	-9999	-0.22	69	69
RAB3GAP2/RIMS1/UNC13B	0.014	0.038	-9999	-0.24	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	-0.005	0.053	-9999	-0.25	12	12
mol:ACh	-0.015	0.038	-9999	-0.1	39	39
RAB3GAP2	0.012	0.027	-9999	-0.42	1	1
STX1A/SNAP25/VAMP2	-0.009	0.057	-9999	-0.17	4	4
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.058	0.1	-9999	-0.22	69	69
UNC13B	0.012	0.027	-9999	-0.42	1	1
CHRNA1	-0.078	0.16	-9999	-0.34	69	69
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.042	0.085	-9999	-0.18	59	59
SNAP25	-0.039	0.086	-9999	-0.26	33	33
VAMP2	0.006	0	-9999	-10000	0	0
SYT1	-0.054	0.13	-9999	-0.29	59	59
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	0.009	0.035	-9999	-0.24	1	1
STX1A/SNAP25 fragment 1/VAMP2	-0.009	0.057	-9999	-0.17	4	4

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.014	0.088	-9999	-0.25	26	26
EPHB2	-0.014	0.1	-9999	-0.4	18	18
Syndecan-2/TACI	-0.049	0.1	-9999	-0.24	46	46
LAMA1	-0.08	0.17	-9999	-0.36	67	67
Syndecan-2/alpha2 ITGB1	-0.007	0.091	-9999	-0.22	31	31
HRAS	0.014	0	-9999	-10000	0	0
Syndecan-2/CASK	-0.007	0.06	-9999	-0.18	27	27
ITGA5	0.004	0.058	-9999	-0.31	8	8
BAX	0.011	0.058	-9999	-10000	0	0
EPB41	0.01	0.037	-9999	-0.42	2	2
positive regulation of cell-cell adhesion	0	0.058	-9999	-0.21	14	14
LAMA3	-0.012	0.089	-9999	-0.3	21	21
EZR	0.007	0.053	-9999	-0.42	4	4
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	0.012	0.027	-9999	-0.42	1	1
Syndecan-2/MMP2	-0.019	0.097	-9999	-0.28	25	25
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	0.001	0.073	-9999	-0.26	19	19
dendrite morphogenesis	-0.014	0.09	-9999	-0.26	25	25
Syndecan-2/GM-CSF	-0.006	0.066	-9999	-0.24	13	13
determination of left/right symmetry	-0.007	0.073	-9999	-0.22	27	27
Syndecan-2/PKC delta	0.002	0.063	-9999	-0.24	13	13
GNB2L1	0.014	0	-9999	-10000	0	0
MAPK3	0.001	0.059	-9999	-0.21	13	13
MAPK1	0.001	0.059	-9999	-0.21	13	13
Syndecan-2/RACK1	0.011	0.053	-9999	-0.19	12	12
NF1	0.009	0.046	-9999	-0.42	3	3
FGFR/FGF/Syndecan-2	-0.007	0.073	-9999	-0.22	27	27
ITGA2	-0.013	0.1	-9999	-0.37	19	19
MAPK8	0.004	0.066	-9999	-0.23	15	15
Syndecan-2/alpha2/beta1 Integrin	-0.041	0.12	-9999	-0.24	60	60
Syndecan-2/Kininogen	-0.005	0.062	-9999	-0.17	29	29
ITGB1	0.013	0.016	-9999	-0.25	1	1
SRC	0.012	0.05	-9999	-0.18	13	13
Syndecan-2/CASK/Protein 4.1	0.001	0.058	-9999	-0.21	14	14
extracellular matrix organization	-0.001	0.078	-9999	-0.31	12	12
actin cytoskeleton reorganization	-0.014	0.088	-9999	-0.25	26	26
Syndecan-2/Caveolin-2/Ras	0.011	0.058	-9999	-0.21	13	13
Syndecan-2/Laminin alpha3	-0.011	0.082	-9999	-0.18	45	45
Syndecan-2/RasGAP	0.016	0.054	-9999	-0.18	14	14
alpha5/beta1 Integrin	0.013	0.044	-9999	-0.23	8	8
PRKCD	0.012	0.027	-9999	-0.42	1	1
Syndecan-2 dimer	-0.014	0.091	-9999	-0.26	25	25
GO:0007205	0.003	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.019	0.053	-9999	-0.17	15	15
RHOA	0.014	0	-9999	-10000	0	0
SDCBP	0.009	0.041	-9999	-0.36	3	3
TNFRSF13B	-0.076	0.15	-9999	-0.33	68	68
RASA1	0.01	0.037	-9999	-0.42	2	2
alpha2/beta1 Integrin	0.001	0.073	-9999	-0.26	19	19
Syndecan-2/Synbindin	0.003	0.061	-9999	-0.24	12	12
TGFB1	0.007	0.053	-9999	-0.42	4	4
CASP3	0.007	0.056	-9999	-0.2	13	13
FN1	-0.014	0.1	-9999	-0.4	18	18
Syndecan-2/IL8	-0.019	0.09	-9999	-0.25	25	25
SDC2	-0.007	0.073	-9999	-0.22	27	27
KNG1	0.002	0.023	-9999	-0.25	2	2
Syndecan-2/Neurofibromin	0	0.066	-9999	-0.24	15	15
TRAPPC4	0.014	0	-9999	-10000	0	0
CSF2	0	0.047	-9999	-0.25	9	9
Syndecan-2/TGFB1	-0.001	0.078	-9999	-0.31	12	12
Syndecan-2/Syntenin/PI-4-5-P2	0.001	0.059	-9999	-0.21	14	14
Syndecan-2/Ezrin	0.008	0.062	-9999	-0.21	16	16
PRKACA	0.005	0.059	-9999	-0.2	15	15
angiogenesis	-0.019	0.089	-9999	-0.25	25	25
MMP2	-0.025	0.12	-9999	-0.34	29	29
IL8	-0.024	0.11	-9999	-0.33	29	29
calcineurin-NFAT signaling pathway	-0.049	0.1	-9999	-0.24	46	46

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.028	0.1	0.34	11	-10000	0	11
GNAI2	0.014	0	-10000	0	-10000	0	0
S1P/S1P5/G12	0.009	0.042	-10000	0	-0.16	14	14
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.068	0.17	-10000	0	-0.41	51	51
RhoA/GTP	-0.029	0.1	-10000	0	-0.34	11	11
negative regulation of cAMP metabolic process	-0.038	0.11	-10000	0	-0.22	68	68
GNAZ	-0.029	0.12	-10000	0	-0.39	28	28
GNAI3	0.014	0	-10000	0	-10000	0	0
GNA12	0.014	0	-10000	0	-10000	0	0
S1PR5	-0.003	0.072	-10000	0	-0.3	14	14
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.038	0.11	-10000	0	-0.22	68	68
RhoA/GDP	0.01	0	-10000	0	-10000	0	0
RHOA	0.014	0	-10000	0	-10000	0	0
GNAI1	0.009	0.046	-10000	0	-0.42	3	3

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.038	0.2	-10000	0	-0.6	23	23
UGCG	0.005	0.058	-10000	0	-0.68	1	1
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.019	0.16	-10000	0	-0.39	34	34
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.005	0.057	-10000	0	-0.67	1	1
mol:DAG	-0.029	0.16	-10000	0	-0.94	8	8
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.07	0.16	-10000	0	-0.45	38	38
FRAP1	-0.027	0.22	-10000	0	-0.52	38	38
FOXO3	-0.02	0.2	-10000	0	-0.51	34	34
AKT1	-0.029	0.22	-10000	0	-0.55	35	35
GAB2	0.012	0.023	-10000	0	-0.25	2	2
SMPD1	0.004	0.07	-10000	0	-0.95	1	1
SGMS1	-0.015	0.14	-10000	0	-0.76	8	8
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	0.041	-10000	0	-0.26	5	5
CALM1	0.014	0	-10000	0	-10000	0	0
cell proliferation	-0.006	0.12	-10000	0	-0.3	25	25
EIF3A	0.014	0	-10000	0	-10000	0	0
PI3K	0.018	0.049	-10000	0	-0.31	5	5
RPS6KB1	0.009	0.043	-10000	0	-0.2	8	8
mol:sphingomyelin	-0.029	0.16	-10000	0	-0.94	8	8
natural killer cell activation	0	0.001	-10000	0	-10000	0	0
JAK3	-0.004	0.086	-10000	0	-0.36	14	14
PIK3R1	0.013	0.038	-10000	0	-0.42	2	2
JAK1	0.016	0.001	-10000	0	-10000	0	0
NFKB1	0.014	0	-10000	0	-10000	0	0
MYC	-0.013	0.18	-10000	0	-0.48	30	30
MYB	-0.014	0.21	-10000	0	-1	10	10
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.041	0.23	-10000	0	-0.56	39	39
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.024	0.042	-10000	0	-0.23	1	1
mol:PI-3-4-5-P3	-0.038	0.22	-10000	0	-0.54	39	39
Rac1/GDP	0.02	0.038	-10000	0	-0.26	4	4
T cell proliferation	-0.033	0.21	-10000	0	-0.5	40	40
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	-0.048	13	13
PRKCZ	-0.036	0.22	-10000	0	-0.52	40	40
NF kappa B1 p50/RelA	-0.011	0.19	-10000	0	-0.44	38	38
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.05	0.22	-10000	0	-0.54	37	37
HSP90AA1	0.012	0.027	-10000	0	-0.42	1	1
RELA	0.014	0	-10000	0	-10000	0	0
IL2RA	-0.034	0.13	-10000	0	-0.39	32	32
IL2RB	-0.029	0.13	-10000	0	-0.37	31	31
TERT	-0.032	0.12	-10000	0	-0.35	33	33
E2F1	0.005	0.088	-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	0.023	13	-10000	0	13
PTPN11	0.014	0.001	-10000	0	-10000	0	0
IL2RG	-0.049	0.15	-10000	0	-0.38	44	44
actin cytoskeleton organization	-0.033	0.21	-10000	0	-0.5	40	40
GRB2	0.014	0.001	-10000	0	-10000	0	0
IL2	0.002	0.031	-10000	0	-0.24	4	4
PIK3CA	0.01	0.049	-10000	0	-0.38	4	4
Rac1/GTP	0.029	0.038	-10000	0	-0.25	4	4
LCK	-0.065	0.16	-10000	0	-0.37	56	56
BCL2	-0.021	0.21	-10000	0	-0.52	34	34

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.013	0.016	-10000	0	-0.25	1	1
RAS family/GTP/Tiam1	-0.005	0.064	-10000	0	-0.19	18	18
NT3 (dimer)/TRKC	-0.03	0.099	-10000	0	-0.21	55	55
NT3 (dimer)/TRKB	-0.07	0.13	-10000	0	-0.29	58	58
SHC/Grb2/SOS1/GAB1/PI3K	0.025	0.053	-10000	0	-0.3	5	5
RAPGEF1	0.014	0	-10000	0	-10000	0	0
BDNF	-0.093	0.17	-10000	0	-0.33	82	82
PIK3CA	0.008	0.048	-10000	0	-0.38	4	4
DYNLT1	0.014	0	-10000	0	-10000	0	0
NTRK1	-0.01	0.089	-10000	0	-0.32	19	19
NTRK2	-0.049	0.14	-10000	0	-0.33	48	48
NTRK3	-0.029	0.11	-10000	0	-0.3	36	36
NT-4/5 (dimer)/TRKB	-0.061	0.13	-10000	0	-0.28	51	51
neuron apoptosis	0.11	0.17	0.36	63	-0.18	1	64
SHC 2-3/Grb2	-0.12	0.18	0.19	1	-0.4	63	64
SHC1	0.014	0	-10000	0	-10000	0	0
SHC2	-0.12	0.21	-10000	0	-0.5	46	46
SHC3	-0.099	0.17	0.18	1	-0.44	40	41
STAT3 (dimer)	0.015	0.042	-10000	0	-0.31	4	4
NT3 (dimer)/TRKA	-0.048	0.11	-10000	0	-0.27	44	44
RIN/GDP	-0.006	0.056	-10000	0	-0.18	2	2
GIPC1	0.014	0	-10000	0	-10000	0	0
KRAS	0.013	0.016	-10000	0	-0.25	1	1
DNAJA3	-0.035	0.1	0.21	1	-0.24	43	44
RIN/GTP	0	0.01	-10000	0	-0.16	1	1
CCND1	0.013	0.087	-10000	0	-0.66	4	4
MAGED1	0.012	0.027	-10000	0	-0.42	1	1
PTPN11	0.014	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	0	0.041	-10000	0	-0.25	7	7
SHC/GRB2/SOS1	0.028	0	-10000	0	-10000	0	0
GRB2	0.014	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.028	0.11	-10000	0	-0.28	36	36
TRKA/NEDD4-2	0.002	0.065	-10000	0	-0.22	20	20
ELMO1	-0.005	0.088	-10000	0	-0.41	12	12
RhoG/GTP/ELMO1/DOCK1	0.007	0.052	-10000	0	-0.23	12	12
NGF	-0.012	0.093	-10000	0	-0.34	19	19
HRAS	0.014	0	-10000	0	-10000	0	0
DOCK1	0.014	0	-10000	0	-10000	0	0
GAB2	0.012	0.023	-10000	0	-0.25	2	2
RIT2	0	0.016	-10000	0	-0.25	1	1
RIT1	0.014	0	-10000	0	-10000	0	0
FRS2	0.013	0.016	-10000	0	-0.25	1	1
DNM1	-0.002	0.074	-10000	0	-0.33	12	12
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	-0.041	0.11	0.2	1	-0.26	48	49
mol:GDP	-0.01	0.077	-10000	0	-0.25	4	4
NGF (dimer)	-0.012	0.093	-10000	0	-0.34	19	19
RhoG/GDP	-0.003	0.062	-10000	0	-0.28	12	12
RIT1/GDP	-0.001	0.057	-10000	0	-0.18	2	2
TIAM1	-0.015	0.11	-10000	0	-0.41	18	18
PIK3R1	0.01	0.037	-10000	0	-0.42	2	2
BDNF (dimer)/TRKB	-0.071	0.13	-10000	0	-0.27	65	65
KIDINS220/CRKL/C3G	0.02	0.011	-10000	0	-10000	0	0
SHC/RasGAP	0.018	0.027	-10000	0	-0.29	2	2
FRS2 family/SHP2	0.027	0.009	-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)	-0.018	0.083	-10000	0	-0.25	29	29
RAP1/GDP	-0.017	0.036	-10000	0	-0.15	2	2
KIDINS220/CRKL	0.013	0.016	-10000	0	-0.25	1	1
BDNF (dimer)	-0.093	0.17	-10000	0	-0.33	82	82
ubiquitin-dependent protein catabolic process	-0.003	0.076	-10000	0	-0.24	20	20
Schwann cell development	-0.029	0.027	-10000	0	-10000	0	0
EHD4	0.014	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.035	0.008	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.033	0.008	-10000	0	-10000	0	0
RAP1B	0.013	0.016	-10000	0	-0.25	1	1
RAP1A	0.014	0	-10000	0	-10000	0	0
CDC42/GTP	-0.097	0.14	-10000	0	-0.33	48	48
ABL1	0.014	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.02	0	-10000	0	-10000	0	0
Rap1/GTP	0	0.058	-10000	0	-10000	0	0
STAT3	0.015	0.042	-10000	0	-0.31	4	4
axon guidance	-0.11	0.12	-10000	0	-0.32	48	48
MAPK3	-0.023	0.099	-10000	0	-0.24	36	36
MAPK1	-0.023	0.099	-10000	0	-0.24	36	36
CDC42/GDP	-0.001	0.057	-10000	0	-0.18	2	2
NTF3	-0.018	0.083	-10000	0	-0.25	29	29
NTF4	0	0.041	-10000	0	-0.25	7	7
NGF (dimer)/TRKA/FAIM	-0.007	0.082	-10000	0	-0.24	24	24
PI3K	0.014	0.048	-10000	0	-0.31	5	5
FRS3	0.014	0	-10000	0	-10000	0	0
FAIM	0.005	0.059	-10000	0	-0.42	5	5
GAB1	0.01	0.037	-10000	0	-0.42	2	2
RASGRF1	-0.08	0.12	0.21	1	-0.25	75	76
SOS1	0.014	0	-10000	0	-10000	0	0
MCF2L	-0.057	0.11	-10000	0	-0.26	44	44
RGS19	0.014	0	-10000	0	-10000	0	0
CDC42	0.014	0	-10000	0	-10000	0	0
RAS family/GTP	0.009	0.053	-10000	0	-10000	0	0
Rac1/GDP	-0.001	0.057	-10000	0	-0.18	3	3
NGF (dimer)/TRKA/GRIT	-0.011	0.074	-10000	0	-0.19	37	37
neuron projection morphogenesis	-0.025	0.1	-10000	0	-0.39	5	5
NGF (dimer)/TRKA/NEDD4-2	-0.003	0.077	-10000	0	-0.24	20	20
MAP2K1	0.029	0.019	-10000	0	-0.19	2	2
NGFR	-0.063	0.14	-10000	0	-0.32	61	61
NGF (dimer)/TRKA/GIPC/GAIP	0.004	0.072	-10000	0	-0.21	23	23
RAS family/GTP/PI3K	0.022	0.036	-10000	0	-0.25	4	4
FRS2 family/SHP2/GRB2/SOS1	0.04	0.008	-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	0.009	0.046	-10000	0	-0.42	3	3
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.014	0	-10000	0	-10000	0	0
PRKCZ	0.005	0.059	-10000	0	-0.42	5	5
MAPKKK cascade	-0.065	0.17	-10000	0	-0.59	23	23
RASA1	0.01	0.037	-10000	0	-0.42	2	2
TRKA/c-Abl	0.004	0.062	-10000	0	-0.21	19	19
SQSTM1	0.012	0.027	-10000	0	-0.42	1	1
BDNF (dimer)/TRKB/GIPC	-0.056	0.12	-10000	0	-0.24	65	65
NGF (dimer)/TRKA/p62/Atypical PKCs	0.007	0.079	-10000	0	-0.2	27	27
MATK	-0.032	0.13	-10000	0	-0.37	32	32
NEDD4L	0.012	0.027	-10000	0	-0.42	1	1
RAS family/GDP	-0.017	0.033	-10000	0	-0.15	2	2
NGF (dimer)/TRKA	-0.042	0.11	0.22	1	-0.26	43	44
Rac1/GTP	-0.062	0.084	-10000	0	-0.23	38	38
FRS2 family/SHP2/CRK family	0.04	0.011	-10000	0	-10000	0	0

×

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	-0.068	0.17	-9999	-0.41	51	51
CDC42/GTP	-0.042	0.12	-9999	-0.38	13	13
PLCG1	-0.045	0.12	-9999	-0.39	13	13
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	-0.042	0.11	-9999	-0.37	13	13
S1PR5	-0.003	0.072	-9999	-0.3	14	14
S1PR4	-0.03	0.12	-9999	-0.36	31	31
MAPK3	-0.045	0.12	-9999	-0.39	13	13
MAPK1	-0.045	0.12	-9999	-0.39	13	13
S1P/S1P5/Gi	-0.038	0.11	-9999	-0.22	68	68
GNAI1	0.009	0.046	-9999	-0.42	3	3
CDC42/GDP	0.01	0	-9999	-10000	0	0
S1P/S1P5/G12	0.009	0.042	-9999	-0.16	14	14
RHOA	0.003	0.062	-9999	-0.19	21	21
S1P/S1P4/Gi	-0.053	0.13	-9999	-0.24	66	66
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.029	0.12	-9999	-0.39	28	28
S1P/S1P4/G12/G13	0.002	0.068	-9999	-0.21	21	21
GNA12	0.014	0	-9999	-10000	0	0
GNA13	0.014	0	-9999	-10000	0	0
CDC42	0.014	0	-9999	-10000	0	0

×

PDGFR-alpha signaling pathway

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
PDGFRA	-0.018	0.11	-9999	-0.37	23	23
PDGF/PDGFRA/CRKL	-0.002	0.076	-9999	-0.27	18	18
positive regulation of JUN kinase activity	0.017	0.058	-9999	-0.2	16	16
CRKL	0.013	0.016	-9999	-0.25	1	1
PDGF/PDGFRA/Caveolin-3	-0.012	0.076	-9999	-0.24	26	26
AP1	0.011	0.067	-9999	-0.39	1	1
mol:IP3	-0.002	0.078	-9999	-0.25	23	23
PLCG1	-0.003	0.078	-9999	-0.25	23	23
PDGF/PDGFRA/alphaV Integrin	-0.008	0.091	-9999	-0.26	27	27
RAPGEF1	0.014	0	-9999	-10000	0	0
CRK	0.014	0	-9999	-10000	0	0
mol:Ca2+	-0.002	0.078	-9999	-0.25	23	23
CAV3	-0.001	0.027	-9999	-0.25	3	3
CAV1	0.012	0.027	-9999	-0.42	1	1
SHC/Grb2/SOS1	0.018	0.058	-9999	-0.2	16	16
PDGF/PDGFRA/Shf	-0.009	0.085	-9999	-0.24	31	31
FOS	0.01	0.067	-9999	-0.39	1	1
JUN	0.001	0.015	-9999	-0.2	1	1
oligodendrocyte development	-0.008	0.091	-9999	-0.26	27	27
GRB2	0.014	0	-9999	-10000	0	0
PIK3R1	0.01	0.037	-9999	-0.42	2	2
mol:DAG	-0.002	0.078	-9999	-0.25	23	23
PDGF/PDGFRA	-0.018	0.11	-9999	-0.37	23	23
actin cytoskeleton reorganization	-0.025	0.1	-9999	-0.25	45	45
SRF	0.017	0.003	-9999	-10000	0	0
SHC1	0.014	0	-9999	-10000	0	0
PI3K	0.004	0.08	-9999	-0.26	18	18
PDGF/PDGFRA/Crk/C3G	0.009	0.064	-9999	-0.22	16	16
JAK1	-0.003	0.075	-9999	-0.24	23	23
ELK1/SRF	0.013	0.059	-9999	-0.21	16	16
SHB	-0.019	0.11	-9999	-0.36	23	23
SHF	0.003	0.061	-9999	-0.33	8	8
CSNK2A1	0.012	0.006	-9999	-10000	0	0
GO:0007205	-0.004	0.083	-9999	-0.31	17	17
SOS1	0.014	0	-9999	-10000	0	0
Ras protein signal transduction	0.017	0.058	-9999	-0.2	16	16
PDGF/PDGFRA/SHB	-0.025	0.1	-9999	-0.25	45	45
PDGF/PDGFRA/Caveolin-1	-0.003	0.078	-9999	-0.24	24	24
ITGAV	0.004	0.061	-9999	-0.39	6	6
ELK1	0.003	0.072	-9999	-0.27	16	16
PIK3CA	0.008	0.048	-9999	-0.38	4	4
PDGF/PDGFRA/Crk	-0.002	0.076	-9999	-0.27	17	17
JAK-STAT cascade	-0.003	0.075	-9999	-0.24	23	23
cell proliferation	-0.009	0.085	-9999	-0.24	31	31

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.012	0.023	-9999	-0.25	2	2
ELF1	-0.015	0.1	-9999	-0.31	27	27
CCNA2	0.009	0.046	-9999	-0.42	3	3
PIK3CA	0.008	0.048	-9999	-0.38	4	4
JAK3	-0.005	0.085	-9999	-0.36	14	14
PIK3R1	0.011	0.037	-9999	-0.42	2	2
JAK1	0.014	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.044	0.24	-9999	-0.58	38	38
SHC1	0.014	0	-9999	-10000	0	0
SP1	0.01	0.054	-9999	-0.31	6	6
IL2RA	-0.047	0.21	-9999	-0.65	27	27
IL2RB	-0.031	0.13	-9999	-0.37	31	31
SOS1	0.014	0	-9999	-10000	0	0
IL2RG	-0.051	0.15	-9999	-0.38	44	44
G1/S transition of mitotic cell cycle	-0.005	0.14	-9999	-0.48	17	17
PTPN11	0.014	0	-9999	-10000	0	0
CCND2	0.004	0.11	-9999	-0.66	6	6
LCK	-0.067	0.16	-9999	-0.37	56	56
GRB2	0.014	0	-9999	-10000	0	0
IL2	0.001	0.031	-9999	-0.25	4	4
CDK6	0.001	0.074	-9999	-0.42	8	8
CCND3	-0.027	0.2	-9999	-0.57	26	26

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	0.022	0.049	0.21	4	-10000	0	4
DAPP1	-0.078	0.24	-10000	0	-0.6	36	36
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.12	0.32	-10000	0	-0.76	42	42
mol:DAG	-0.03	0.12	0.17	1	-0.27	41	42
HRAS	0.014	0.002	-10000	0	-10000	0	0
RAP1A	0.014	0.003	-10000	0	-10000	0	0
ARF5/GDP	-0.005	0.11	-10000	0	-0.28	27	27
PLCG2	-0.004	0.083	-10000	0	-0.38	12	12
PLCG1	0.014	0	-10000	0	-10000	0	0
ARF5	0.014	0	-10000	0	-10000	0	0
mol:GTP	0.01	0.049	0.2	4	-10000	0	4
ARF1/GTP	0.019	0.052	0.21	4	-10000	0	4
RHOA	0.014	0	-10000	0	-10000	0	0
YES1	0.007	0.053	-10000	0	-0.42	4	4
RAP1A/GTP	0.014	0.049	0.2	4	-10000	0	4
ADAP1	0.005	0.06	0.2	3	-0.18	11	14
ARAP3	0.01	0.049	0.2	4	-0.16	16	20
INPPL1	0.014	0	-10000	0	-10000	0	0
PREX1	0.002	0.069	-10000	0	-0.42	7	7
ARHGEF6	-0.008	0.093	-10000	0	-0.42	13	13
ARHGEF7	0.014	0	-10000	0	-10000	0	0
ARF1	0.014	0	-10000	0	-10000	0	0
NRAS	0.014	0.002	-10000	0	-10000	0	0
FYN	0.014	0	-10000	0	-10000	0	0
ARF6	0.014	0	-10000	0	-10000	0	0
FGR	-0.008	0.091	-10000	0	-0.37	15	15
mol:Ca2+	-0.009	0.06	-10000	0	-0.15	24	24
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	-0.015	0.11	-10000	0	-0.41	18	18
ZAP70	-0.062	0.15	-10000	0	-0.34	57	57
mol:IP3	-0.016	0.083	-10000	0	-0.2	32	32
LYN	0.009	0.046	-10000	0	-0.42	3	3
ARF1/GDP	-0.005	0.11	-10000	0	-0.28	27	27
RhoA/GDP	0.014	0.074	0.21	2	-0.26	9	11
PDK1/Src/Hsp90	0.026	0.023	-10000	0	-0.24	2	2
BLNK	-0.041	0.14	-10000	0	-0.39	36	36
actin cytoskeleton reorganization	0.007	0.1	0.21	2	-0.31	18	20
SRC	0.012	0.027	-10000	0	-0.42	1	1
PLEKHA2	0.006	0.064	-10000	0	-0.25	14	14
RAC1	0.014	0	-10000	0	-10000	0	0
PTEN	0.006	0.05	-10000	0	-0.4	4	4
HSP90AA1	0.012	0.027	-10000	0	-0.42	1	1
ARF6/GTP	0.022	0.047	0.21	4	-10000	0	4
RhoA/GTP	0.018	0.047	0.2	4	-10000	0	4
Src family/SYK family/BLNK-LAT	-0.12	0.31	-10000	0	-0.72	43	43
BLK	-0.082	0.16	-10000	0	-0.33	74	74
PDPK1	0.014	0	-10000	0	-10000	0	0
CYTH1	0.015	0.047	0.2	4	-10000	0	4
HCK	-0.011	0.1	-10000	0	-0.42	15	15
CYTH3	0.015	0.048	0.2	4	-0.18	1	5
CYTH2	0.015	0.047	0.2	4	-10000	0	4
KRAS	0.013	0.016	-10000	0	-0.25	1	1
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.024	0.059	-10000	0	-0.38	4	4
SGK1	0.019	0.062	-10000	0	-0.4	4	4
INPP5D	-0.011	0.097	-10000	0	-0.39	16	16
mol:GDP	-0.014	0.11	-10000	0	-0.3	27	27
SOS1	0.014	0	-10000	0	-10000	0	0
SYK	-0.009	0.094	-10000	0	-0.39	15	15
ARF6/GDP	0.012	0.074	0.21	2	-0.26	9	11
mol:PI-3-4-5-P3	-0.006	0.048	0.23	4	-10000	0	4
ARAP3/RAP1A/GTP	0.014	0.049	0.2	4	-10000	0	4
VAV1	-0.032	0.13	-10000	0	-0.4	29	29
mol:PI-3-4-P2	0.002	0.068	-10000	0	-0.26	16	16
RAS family/GTP/PI3K Class I	0.017	0.045	-10000	0	-0.16	16	16
PLEKHA1	0.006	0.061	-10000	0	-0.24	15	15
Rac1/GDP	-0.005	0.11	-10000	0	-0.28	27	27
LAT	-0.019	0.11	-10000	0	-0.34	25	25
Rac1/GTP	-0.023	0.15	-10000	0	-0.4	28	28
ITK	-0.019	0.08	0.2	1	-0.19	33	34
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.05	0.17	0.2	1	-0.4	41	42
LCK	-0.067	0.16	-10000	0	-0.37	56	56
BTK	0.004	0.061	0.2	2	-0.19	12	14

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.002	0.082	-10000	0	-0.24	21	21
ER alpha/Gai/GDP/Gbeta gamma	-0.051	0.15	-10000	0	-0.3	55	55
AKT1	-0.015	0.16	-10000	0	-0.71	13	13
PIK3CA	0.008	0.048	-10000	0	-0.38	4	4
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.018	0.16	-10000	0	-0.72	13	13
mol:Ca2+	-0.02	0.11	-10000	0	-0.3	23	23
IGF1R	0.009	0.041	-10000	0	-0.36	3	3
E2/ER alpha (dimer)/Striatin	0.003	0.061	-10000	0	-0.23	17	17
SHC1	0.014	0	-10000	0	-10000	0	0
apoptosis	0.014	0.15	0.67	13	-10000	0	13
RhoA/GTP	-0.007	0.032	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.059	0.11	-10000	0	-0.38	18	18
regulation of stress fiber formation	-0.024	0.046	0.29	1	-10000	0	1
E2/ERA-ERB (dimer)	-0.012	0.076	-10000	0	-0.17	43	43
KRAS	0.013	0.016	-10000	0	-0.25	1	1
G13/GTP	0.008	0.046	-10000	0	-0.22	10	10
pseudopodium formation	0.024	0.046	-10000	0	-0.29	1	1
E2/ER alpha (dimer)/PELP1	0.008	0.051	-10000	0	-0.24	10	10
GRB2	0.014	0	-10000	0	-10000	0	0
GNG2	-0.003	0.082	-10000	0	-0.42	10	10
GNAO1	-0.068	0.17	-10000	0	-0.41	51	51
HRAS	0.014	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.03	0.13	-10000	0	-0.45	16	16
E2/ER beta (dimer)	-0.014	0.065	-10000	0	-0.18	33	33
mol:GDP	-0.022	0.071	-10000	0	-0.32	13	13
mol:NADP	-0.03	0.13	-10000	0	-0.45	16	16
PIK3R1	0.01	0.037	-10000	0	-0.42	2	2
mol:IP3	-0.021	0.11	-10000	0	-0.32	23	23
IGF-1R heterotetramer	0.009	0.041	-10000	0	-0.36	3	3
PLCB1	-0.02	0.098	-10000	0	-0.31	17	17
PLCB2	-0.007	0.094	-10000	0	-0.35	14	14
IGF1	-0.023	0.12	-10000	0	-0.38	25	25
mol:L-citrulline	-0.03	0.13	-10000	0	-0.45	16	16
RHOA	0.014	0	-10000	0	-10000	0	0
Gai/GDP	-0.1	0.26	-10000	0	-0.64	48	48
JNK cascade	-0.014	0.064	-10000	0	-0.18	33	33
BCAR1	0.01	0.037	-10000	0	-0.42	2	2
ESR2	-0.021	0.095	-10000	0	-0.27	33	33
GNAQ	0.014	0	-10000	0	-10000	0	0
ESR1	-0.005	0.085	-10000	0	-0.39	12	12
Gq family/GDP/Gbeta gamma	0.002	0.09	-10000	0	-0.39	9	9
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.012	0.054	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.058	0.11	-10000	0	-0.38	18	18
GNAZ	-0.029	0.12	-10000	0	-0.39	28	28
E2/ER alpha (dimer)	-0.003	0.06	-10000	0	-0.27	12	12
STRN	0.005	0.059	-10000	0	-0.42	5	5
GNAL	-0.069	0.15	-10000	0	-0.32	66	66
PELP1	0.014	0	-10000	0	-10000	0	0
MAPK11	-0.009	0.063	-10000	0	-0.16	38	38
GNAI2	0.014	0	-10000	0	-10000	0	0
GNAI3	0.014	0	-10000	0	-10000	0	0
GNAI1	0.009	0.046	-10000	0	-0.42	3	3
HBEGF	-0.062	0.14	-10000	0	-0.34	34	34
cAMP biosynthetic process	-0.044	0.092	-10000	0	-0.21	52	52
SRC	-0.044	0.14	-10000	0	-0.41	18	18
PI3K	0.014	0.048	-10000	0	-0.31	5	5
GNB1	0.014	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	0.003	0.083	-10000	0	-0.3	13	13
SOS1	0.014	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.059	0.097	-10000	0	-0.32	22	22
Gs family/GTP	-0.042	0.095	-10000	0	-0.21	52	52
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.026	0.008	-10000	0	-10000	0	0
vasodilation	-0.028	0.12	-10000	0	-0.43	16	16
mol:DAG	-0.021	0.11	-10000	0	-0.32	23	23
Gs family/GDP/Gbeta gamma	-0.048	0.085	-10000	0	-0.3	17	17
MSN	0.024	0.049	-10000	0	-0.32	1	1
Gq family/GTP	-0.006	0.078	-10000	0	-0.36	7	7
mol:PI-3-4-5-P3	-0.016	0.16	-10000	0	-0.69	13	13
NRAS	0.014	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.028	0.12	0.43	16	-10000	0	16
GRB2/SOS1	0.02	0	-10000	0	-10000	0	0
RhoA/GDP	0.006	0.075	-10000	0	-0.3	13	13
NOS3	-0.032	0.14	-10000	0	-0.47	16	16
GNA11	0.014	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.013	0.13	-10000	0	-0.48	15	15
E2/ER alpha (dimer)/PELP1/Src	-0.035	0.13	-10000	0	-0.39	18	18
ruffle organization	0.024	0.046	-10000	0	-0.29	1	1
ROCK2	0.022	0.047	-10000	0	-10000	0	0
GNA14	-0.028	0.1	-10000	0	-0.27	39	39
GNA15	-0.003	0.081	-10000	0	-0.39	11	11
GNA13	0.014	0	-10000	0	-10000	0	0
MMP9	-0.069	0.15	-10000	0	-0.37	34	34
MMP2	-0.054	0.14	-10000	0	-0.37	24	24

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.018	0.098	-10000	0	-0.25	38	38
CRKL	-0.013	0.1	-10000	0	-0.54	3	3
mol:PIP3	-0.007	0.049	0.39	4	-10000	0	4
AKT1	0.005	0.035	0.28	4	-10000	0	4
PTK2B	0.009	0.038	-10000	0	-0.29	4	4
RAPGEF1	-0.007	0.097	-10000	0	-0.5	3	3
RANBP10	0.014	0	-10000	0	-10000	0	0
PIK3CA	0.008	0.048	-10000	0	-0.38	4	4
HGF/MET/SHIP2	-0.027	0.099	-10000	0	-0.24	39	39
MAP3K5	-0.016	0.11	-10000	0	-0.38	9	9
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.016	0.094	-10000	0	-0.22	39	39
AP1	0.001	0.041	-10000	0	-0.27	1	1
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.014	0	-10000	0	-10000	0	0
apoptosis	0.007	0.027	-10000	0	-10000	0	0
STAT3 (dimer)	-0.009	0.087	-10000	0	-0.39	2	2
GAB1/CRKL/SHP2/PI3K	0.003	0.1	-10000	0	-0.72	2	2
INPP5D	-0.011	0.097	-10000	0	-0.39	16	16
CBL/CRK	-0.005	0.098	-10000	0	-0.5	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	0.007	0.053	-10000	0	-0.42	4	4
ELK1	-0.022	0.049	-10000	0	-0.15	26	26
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.003	0.059	-10000	0	-0.22	4	4
PAK1	0.009	0.034	0.27	4	-10000	0	4
HGF/MET/RANBP10	-0.027	0.099	-10000	0	-0.24	39	39
HRAS	-0.044	0.18	-10000	0	-0.54	27	27
DOCK1	-0.007	0.097	-10000	0	-0.5	3	3
GAB1	-0.019	0.11	-10000	0	-0.26	28	28
CRK	-0.013	0.1	-10000	0	-0.54	3	3
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.048	0.18	-10000	0	-0.46	39	39
JUN	0.013	0.016	-10000	0	-0.25	1	1
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.027	0.08	-10000	0	-0.21	41	41
PIK3R1	0.01	0.037	-10000	0	-0.42	2	2
cell morphogenesis	0.002	0.1	-10000	0	-0.55	2	2
GRB2/SHC	-0.008	0.074	-10000	0	-0.19	29	29
FOS	0.006	0.045	-10000	0	-0.25	8	8
GLMN	-0.003	0.024	-10000	0	-0.22	3	3
cell motility	-0.022	0.049	-10000	0	-0.15	26	26
HGF/MET/MUC20	-0.035	0.098	-10000	0	-0.24	39	39
cell migration	-0.009	0.073	-10000	0	-0.19	29	29
GRB2	0.014	0	-10000	0	-10000	0	0
CBL	0.014	0	-10000	0	-10000	0	0
MET/RANBP10	-0.018	0.098	-10000	0	-0.29	27	27
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.013	0.087	-10000	0	-0.2	41	41
MET/MUC20	-0.028	0.096	-10000	0	-0.26	38	38
RAP1B	-0.002	0.091	-10000	0	-0.58	2	2
RAP1A	-0.002	0.091	-10000	0	-0.58	2	2
HGF/MET/RANBP9	-0.027	0.099	-10000	0	-0.24	39	39
RAF1	-0.036	0.17	-10000	0	-0.51	27	27
STAT3	-0.009	0.088	-10000	0	-0.4	2	2
cell proliferation	-0.016	0.12	-10000	0	-0.3	39	39
RPS6KB1	-0.005	0.035	-10000	0	-10000	0	0
MAPK3	-0.025	0.044	-10000	0	-10000	0	0
MAPK1	-0.025	0.044	-10000	0	-10000	0	0
RANBP9	0.014	0	-10000	0	-10000	0	0
MAPK8	-0.002	0.11	-10000	0	-0.52	5	5
SRC	-0.008	0.082	-10000	0	-0.36	2	2
PI3K	-0.013	0.083	-10000	0	-0.2	32	32
MET/Glomulin	-0.023	0.086	-10000	0	-0.22	41	41
SOS1	0.014	0	-10000	0	-10000	0	0
MAP2K1	-0.028	0.16	-10000	0	-0.47	27	27
MET	-0.041	0.14	-10000	0	-0.37	38	38
MAP4K1	-0.02	0.11	-10000	0	-0.39	7	7
PTK2	0.014	0	-10000	0	-10000	0	0
MAP2K2	-0.028	0.16	-10000	0	-0.47	27	27
BAD	0.01	0.032	0.27	4	-10000	0	4
MAP2K4	-0.009	0.1	-10000	0	-0.37	7	7
SHP2/GRB2/SOS1/GAB1	-0.04	0.099	-10000	0	-0.3	28	28
INPPL1	0.014	0	-10000	0	-10000	0	0
PXN	0.014	0	-10000	0	-10000	0	0
SH3KBP1	0.012	0.027	-10000	0	-0.42	1	1
HGS	-0.019	0.074	-10000	0	-0.19	41	41
PLCgamma1/PKC	0.01	0	-10000	0	-10000	0	0
HGF	-0.023	0.11	-10000	0	-0.32	29	29
RASA1	0.01	0.037	-10000	0	-0.42	2	2
NCK1	0.014	0	-10000	0	-10000	0	0
PTPRJ	0.01	0.037	-10000	0	-0.42	2	2
NCK/PLCgamma1	-0.008	0.075	-10000	0	-0.18	41	41
PDPK1	0	0.039	0.32	4	-10000	0	4
HGF/MET/SHIP	-0.04	0.12	-10000	0	-0.27	46	46

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.014	0	-9999	-10000	0	0
LAT2	-0.026	0.15	-9999	-0.5	17	17
AP1	-0.021	0.18	-9999	-0.53	22	22
mol:PIP3	-0.039	0.18	-9999	-0.5	27	27
IKBKB	-0.015	0.1	-9999	-0.27	27	27
AKT1	-0.004	0.088	-9999	-0.33	8	8
IKBKG	-0.015	0.1	-9999	-0.28	25	25
MS4A2	-0.005	0.069	-9999	-0.29	14	14
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.008	0.049	-9999	-0.38	4	4
MAP3K1	-0.019	0.15	-9999	-0.42	25	25
mol:Ca2+	-0.025	0.13	-9999	-0.36	27	27
LYN	0.008	0.048	-9999	-0.44	3	3
CBLB	-0.017	0.12	-9999	-0.43	14	14
SHC1	0.014	0	-9999	-10000	0	0
RasGAP/p62DOK	0.02	0.035	-9999	-0.21	4	4
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	-0.011	0.097	-9999	-0.39	16	16
PLD2	-0.018	0.093	-9999	-0.22	34	34
PTPN13	-0.02	0.13	-9999	-0.54	10	10
PTPN11	0.012	0.008	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	0.008	0.088	-9999	-0.32	9	9
SYK	-0.01	0.096	-9999	-0.4	15	15
GRB2	0.013	0	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.073	0.17	-9999	-0.49	29	29
LAT	-0.032	0.14	-9999	-0.46	18	18
PAK2	-0.024	0.17	-9999	-0.51	21	21
NFATC2	-0.048	0.15	-9999	-0.48	24	24
HRAS	-0.033	0.18	-9999	-0.57	21	21
GAB2	0.012	0.023	-9999	-0.25	2	2
PLA2G1B	0.024	0.014	-9999	-10000	0	0
Fc epsilon R1	-0.036	0.12	-9999	-0.29	38	38
Antigen/IgE/Fc epsilon R1	-0.031	0.11	-9999	-0.26	38	38
mol:GDP	-0.042	0.2	-9999	-0.56	26	26
JUN	0.013	0.016	-9999	-0.25	1	1
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.01	0.038	-9999	-0.42	2	2
FOS	0.006	0.045	-9999	-0.25	8	8
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.023	0.13	-9999	-0.46	14	14
CHUK	-0.016	0.1	-9999	-0.27	27	27
KLRG1	-0.02	0.12	-9999	-0.47	11	11
VAV1	-0.036	0.16	-9999	-0.49	22	22
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.017	0.12	-9999	-0.45	13	13
negative regulation of mast cell degranulation	-0.022	0.14	-9999	-0.52	15	15
BTK	-0.043	0.21	-9999	-0.67	21	21
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.032	0.15	-9999	-0.38	28	28
GAB2/PI3K/SHP2	-0.038	0.079	-9999	-0.36	8	8
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.032	0.15	-9999	-0.46	18	18
RAF1	0.015	0.016	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.036	0.14	-9999	-0.3	43	43
FCER1G	-0.023	0.11	-9999	-0.32	29	29
FCER1A	-0.04	0.13	-9999	-0.35	38	38
Antigen/IgE/Fc epsilon R1/Fyn	-0.021	0.1	-9999	-0.23	38	38
MAPK3	0.023	0.014	-9999	-10000	0	0
MAPK1	0.023	0.014	-9999	-10000	0	0
NFKB1	0.014	0	-9999	-10000	0	0
MAPK8	0.007	0.082	-9999	-0.63	3	3
DUSP1	0.007	0.044	-9999	-0.28	6	6
NF-kappa-B/RelA	-0.023	0.052	-9999	-0.19	14	14
actin cytoskeleton reorganization	-0.014	0.13	-9999	-0.59	9	9
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.025	0.17	-9999	-0.51	22	22
FER	-0.02	0.13	-9999	-0.39	17	17
RELA	0.014	0	-9999	-10000	0	0
ITK	-0.051	0.14	-9999	-0.37	38	38
SOS1	0.014	0	-9999	-10000	0	0
PLCG1	-0.039	0.2	-9999	-0.61	22	22
cytokine secretion	-0.017	0.037	-9999	-0.15	9	9
SPHK1	-0.026	0.14	-9999	-0.48	15	15
PTK2	-0.016	0.14	-9999	-0.62	9	9
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.071	0.17	-9999	-0.53	25	25
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.03	0.17	-9999	-0.49	23	23
MAP2K2	0.019	0.014	-9999	-10000	0	0
MAP2K1	0.019	0.014	-9999	-10000	0	0
MAP2K7	0.014	0	-9999	-10000	0	0
KLRG1/SHP2	-0.017	0.11	-9999	-0.46	10	10
MAP2K4	0.019	0.009	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.034	0.12	-9999	-0.28	41	41
mol:Choline	-0.018	0.092	-9999	-0.22	34	34
SHC/Grb2/SOS1	-0.002	0.12	-9999	-0.52	9	9
FYN	0.014	0	-9999	-10000	0	0
DOK1	0.011	0.031	-9999	-0.33	2	2
PXN	-0.009	0.13	-9999	-0.56	9	9
HCLS1	-0.028	0.16	-9999	-0.53	17	17
PRKCB	-0.032	0.14	-9999	-0.37	30	30
FCGR2B	-0.007	0.085	-9999	-0.33	16	16
IGHE	-0.001	0.004	-9999	-10000	0	0
KLRG1/SHIP	-0.023	0.15	-9999	-0.53	15	15
LCP2	-0.011	0.1	-9999	-0.42	15	15
PLA2G4A	-0.026	0.14	-9999	-0.43	17	17
RASA1	0.01	0.037	-9999	-0.42	2	2
mol:Phosphatidic acid	-0.018	0.092	-9999	-0.22	34	34
IKK complex	-0.002	0.078	-9999	-0.21	21	21
WIPF1	-0.001	0.078	-9999	-0.42	9	9

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.015	0.091	-10000	0	-0.18	53	53
positive regulation of NF-kappaB transcription factor activity	0	0.001	-10000	0	-10000	0	0
CRKL	0.013	0.016	-10000	0	-0.25	1	1
STAT1 (dimer)/Cbp/p300	0.003	0.092	-10000	0	-0.26	8	8
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.011	0.044	-10000	0	-0.25	5	5
antigen processing and presentation of peptide antigen via MHC class I	-0.033	0.075	-10000	0	-0.25	20	20
CaM/Ca2+	-0.011	0.084	-10000	0	-0.17	53	53
RAP1A	0.014	0	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	-0.013	0.09	-10000	0	-0.18	53	53
AKT1	-0.008	0.089	-10000	0	-0.41	4	4
MAP2K1	-0.013	0.092	-10000	0	-0.31	9	9
MAP3K11	-0.015	0.084	-10000	0	-0.2	9	9
IFNGR1	0.009	0.011	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.03	0.11	-10000	0	-0.31	28	28
Rap1/GTP	-0.028	0.049	-10000	0	-0.26	1	1
CRKL/C3G	0.02	0.011	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.014	0.096	-10000	0	-0.19	53	53
CEBPB	0.004	0.13	-10000	0	-0.49	12	12
STAT3	0.014	0	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.025	0.16	-10000	0	-1.1	4	4
STAT1	-0.016	0.088	-10000	0	-0.18	53	53
CALM1	0.014	0	-10000	0	-10000	0	0
IFN-gamma (dimer)	-0.085	0.17	-10000	0	-0.37	67	67
PIK3CA	0.008	0.048	-10000	0	-0.38	4	4
STAT1 (dimer)/PIAS1	-0.008	0.086	-10000	0	-0.25	7	7
CEBPB/PTGES2/Cbp/p300	-0.025	0.067	-10000	0	-0.3	12	12
mol:Ca2+	-0.016	0.089	-10000	0	-0.18	53	53
MAPK3	-0.003	0.1	-10000	0	-0.42	7	7
STAT1 (dimer)	-0.042	0.1	-10000	0	-0.36	18	18
MAPK1	-0.003	0.1	-10000	0	-0.46	5	5
JAK2	0	0.062	-10000	0	-0.39	6	6
PIK3R1	0.01	0.037	-10000	0	-0.42	2	2
JAK1	0.009	0.011	-10000	0	-10000	0	0
CAMK2D	0.012	0.027	-10000	0	-0.42	1	1
DAPK1	0.008	0.12	-10000	0	-0.53	10	10
SMAD7	0.007	0.055	-10000	0	-0.15	13	13
CBL/CRKL/C3G	-0.001	0.079	-10000	0	-0.31	1	1
PI3K	-0.015	0.093	-10000	0	-0.31	8	8
IFNG	-0.085	0.17	-10000	0	-0.37	67	67
apoptosis	0.001	0.099	-10000	0	-0.38	12	12
CAMK2G	0.014	0	-10000	0	-10000	0	0
STAT3 (dimer)	0.014	0	-10000	0	-10000	0	0
CAMK2A	-0.037	0.12	-10000	0	-0.3	42	42
CAMK2B	-0.036	0.12	-10000	0	-0.3	42	42
FRAP1	-0.008	0.083	-10000	0	-0.38	4	4
PRKCD	-0.008	0.09	-10000	0	-0.34	6	6
RAP1B	0.013	0.016	-10000	0	-0.25	1	1
negative regulation of cell growth	-0.033	0.075	-10000	0	-0.25	20	20
PTPN2	0.012	0.027	-10000	0	-0.42	1	1
EP300	0.014	0.001	-10000	0	-10000	0	0
IRF1	-0.001	0.1	-10000	0	-0.33	14	14
STAT1 (dimer)/PIASy	-0.009	0.087	0.18	3	-0.28	5	8
SOCS1	-0.005	0.16	-10000	0	-1.3	4	4
mol:GDP	-0.003	0.076	-10000	0	-0.3	1	1
CASP1	-0.001	0.079	-10000	0	-0.25	19	19
PTGES2	0.014	0	-10000	0	-10000	0	0
IRF9	0.024	0.043	-10000	0	-0.14	4	4
mol:PI-3-4-5-P3	-0.04	0.077	-10000	0	-0.3	8	8
RAP1/GDP	-0.028	0.05	-10000	0	-0.27	1	1
CBL	-0.015	0.083	-10000	0	-0.19	15	15
MAP3K1	-0.019	0.096	-10000	0	-0.25	16	16
PIAS1	0.014	0	-10000	0	-10000	0	0
PIAS4	0.014	0.001	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.033	0.075	-10000	0	-0.25	20	20
PTPN11	-0.021	0.086	-10000	0	-0.18	53	53
CREBBP	0.014	0.001	-10000	0	-10000	0	0
RAPGEF1	0.014	0	-10000	0	-10000	0	0

×

Ceramide signaling pathway

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
SPHK2	-0.015	0.092	-10000	0	-0.25	33	33
MAP4K4	-0.004	0.095	-10000	0	-0.39	9	9
BAG4	0.005	0.059	-10000	0	-0.42	5	5
PKC zeta/ceramide	-0.003	0.048	0.12	15	-0.21	4	19
NFKBIA	0.014	0	-10000	0	-10000	0	0
BIRC3	-0.058	0.15	-10000	0	-0.36	51	51
BAX	0.004	0.022	-10000	0	-10000	0	0
RIPK1	0.014	0	-10000	0	-10000	0	0
AKT1	0.013	0.007	-10000	0	-10000	0	0
BAD	-0.002	0.042	0.12	16	-10000	0	16
SMPD1	0.002	0.053	-10000	0	-0.18	16	16
RB1	-0.006	0.05	0.12	15	-0.22	4	19
FADD/Caspase 8	0.004	0.095	-10000	0	-0.4	9	9
MAP2K4	-0.001	0.051	0.12	16	-0.21	6	22
NSMAF	0.014	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.003	0.04	0.12	15	-10000	0	15
EGF	-0.088	0.17	-10000	0	-0.37	71	71
mol:ceramide	-0.007	0.045	0.12	19	-10000	0	19
MADD	0.014	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.017	0.097	-10000	0	-0.26	34	34
ASAH1	0.007	0.053	-10000	0	-0.42	4	4
negative regulation of cell cycle	-0.006	0.049	0.12	15	-0.22	4	19
cell proliferation	0	0.053	-10000	0	-0.17	17	17
BID	0.002	0.071	-10000	0	-0.28	9	9
MAP3K1	-0.006	0.053	0.12	16	-0.22	6	22
EIF2A	0.008	0.039	-10000	0	-10000	0	0
TRADD	0.014	0	-10000	0	-10000	0	0
CRADD	0.013	0.016	-10000	0	-0.25	1	1
MAPK3	0.011	0.038	0.12	15	-10000	0	15
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.011	0.038	0.12	15	-10000	0	15
Cathepsin D/ceramide	-0.002	0.047	0.12	16	-0.17	4	20
FADD	-0.004	0.094	-10000	0	-0.41	8	8
KSR1	-0.002	0.042	0.11	18	-0.098	1	19
MAPK8	-0.001	0.065	0.12	15	-0.29	7	22
PRKRA	-0.002	0.042	0.12	16	-10000	0	16
PDGFA	-0.031	0.13	-10000	0	-0.37	31	31
TRAF2	0.014	0	-10000	0	-10000	0	0
IGF1	-0.023	0.12	-10000	0	-0.38	25	25
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.007	0.045	0.12	19	-10000	0	19
CTSD	0.008	0.044	-10000	0	-0.33	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	0.008	0.063	-10000	0	-0.18	17	17
PRKCD	0.012	0.027	-10000	0	-0.42	1	1
PRKCZ	0.005	0.059	-10000	0	-0.42	5	5
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.017	0.097	-10000	0	-0.26	34	34
RelA/NF kappa B1	0.02	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	-0.033	0.13	-10000	0	-0.41	29	29
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.009	0.1	-10000	0	-0.44	8	8
TNFR1A/BAG4/TNF-alpha	0	0.075	-10000	0	-0.24	20	20
mol:Sphingosine-1-phosphate	-0.015	0.092	-10000	0	-0.25	33	33
MAP2K1	0.008	0.038	0.12	15	-10000	0	15
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.014	0	-10000	0	-10000	0	0
CYCS	0.006	0.038	0.14	8	-10000	0	8
TNFRSF1A	0.014	0	-10000	0	-10000	0	0
NFKB1	0.014	0	-10000	0	-10000	0	0
TNFR1A/BAG4	0.014	0.042	-10000	0	-0.29	5	5
EIF2AK2	0.004	0.04	0.12	16	-10000	0	16
TNF-alpha/TNFR1A/FAN	0.005	0.068	-10000	0	-0.24	15	15
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.01	0.067	-10000	0	-0.26	9	9
MAP2K2	0.008	0.038	-10000	0	-10000	0	0
SMPD3	0.002	0.058	-10000	0	-0.2	15	15
TNF	-0.025	0.11	-10000	0	-0.34	29	29
PKC zeta/PAR4	-0.019	0.1	-10000	0	-0.28	34	34
mol:PHOSPHOCHOLINE	0.045	0.087	0.18	69	-10000	0	69
NF kappa B1/RelA/I kappa B alpha	0.012	0.076	-10000	0	-0.19	33	33
AIFM1	0.006	0.038	0.14	8	-10000	0	8
BCL2	0.001	0.074	-10000	0	-0.42	8	8

×

S1P1 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.01	0.044	-9999	-0.18	11	11
PDGFRB	0.01	0.038	-9999	-0.42	2	2
SPHK1	-0.03	0.12	-9999	-0.73	7	7
mol:S1P	-0.019	0.12	-9999	-0.56	9	9
S1P1/S1P/Gi	-0.062	0.16	-9999	-0.36	41	41
GNAO1	-0.069	0.17	-9999	-0.41	51	51
PDGFB-D/PDGFRB/PLCgamma1	-0.047	0.14	-9999	-0.33	37	37
PLCG1	-0.054	0.15	-9999	-0.34	41	41
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.01	0.038	-9999	-0.42	2	2
GNAI2	0.013	0.005	-9999	-10000	0	0
GNAI3	0.013	0.004	-9999	-10000	0	0
GNAI1	0.008	0.046	-9999	-0.42	3	3
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.005	0.036	-9999	-0.19	4	4
S1P1/S1P	-0.012	0.098	-9999	-0.46	8	8
negative regulation of cAMP metabolic process	-0.06	0.16	-9999	-0.36	41	41
MAPK3	-0.068	0.19	-9999	-0.47	35	35
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	0.009	0.038	-9999	-0.29	4	4
PLCB2	-0.011	0.1	-9999	-0.38	12	12
RAC1	0.014	0	-9999	-10000	0	0
RhoA/GTP	-0.026	0.075	-9999	-0.39	8	8
receptor internalization	-0.011	0.091	-9999	-0.43	8	8
PTGS2	-0.094	0.28	-9999	-0.94	21	21
Rac1/GTP	-0.026	0.075	-9999	-0.39	8	8
RHOA	0.014	0	-9999	-10000	0	0
VEGFA	0.004	0.052	-9999	-0.27	9	9
negative regulation of T cell proliferation	-0.06	0.16	-9999	-0.36	41	41
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.03	0.13	-9999	-0.39	28	28
MAPK1	-0.068	0.19	-9999	-0.47	35	35
S1P1/S1P/PDGFB-D/PDGFRB	-0.008	0.099	-9999	-0.43	8	8
ABCC1	0.003	0.065	-9999	-0.42	6	6

×

Signaling mediated by p38-gamma and p38-delta

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.013	0.044	-9999	-0.24	7	7
SNTA1	0.007	0.051	-9999	-0.35	5	5
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.011	0.049	-9999	-0.24	9	9
MAPK12	-0.009	0.093	-9999	-0.24	31	31
CCND1	-0.002	0.062	-9999	-0.28	8	8
p38 gamma/SNTA1	-0.004	0.09	-9999	-0.22	34	34
MAP2K3	0.014	0	-9999	-10000	0	0
PKN1	0.012	0.027	-9999	-0.42	1	1
G2/M transition checkpoint	-0.009	0.092	-9999	-0.24	31	31
MAP2K6	0.001	0.072	-9999	-0.27	16	16
MAPT	-0.026	0.1	-9999	-0.27	35	35
MAPK13	0.009	0.052	-9999	-0.25	10	10
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.004	0.062	-9999	-0.33	8	8

×

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	-0.025	0.086	-10000	0	-0.21	37	37
MAPK9	0.007	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.001	0.018	-10000	0	-0.16	3	3
GNB1/GNG2	0.009	0.05	-10000	0	-0.24	10	10
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	0.007	0	-10000	0	-10000	0	0
Gs family/GTP	-0.034	0.078	-10000	0	-0.16	66	66
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	0.021	0.047	66	-10000	0	66
GNAL	-0.069	0.15	-10000	0	-0.32	66	66
GNG2	-0.003	0.082	-10000	0	-0.42	10	10
CRH	-0.002	0.026	-10000	0	-0.25	3	3
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.004	0.031	-10000	0	-0.29	3	3
MAPK11	0.002	0.04	-10000	0	-0.29	5	5

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.019	0.11	-9999	-0.28	37	37
CRKL	0.013	0.016	-9999	-0.25	1	1
Rac1/GDP	0.01	0	-9999	-10000	0	0
DOCK1	0.014	0	-9999	-10000	0	0
ITGA4	-0.031	0.13	-9999	-0.38	30	30
alpha4/beta7 Integrin/MAdCAM1	-0.012	0.097	-9999	-0.23	38	38
EPO	0	0.047	-9999	-0.25	9	9
alpha4/beta7 Integrin	-0.03	0.12	-9999	-0.29	43	43
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.014	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.012	0.09	-9999	-0.26	31	31
EPO/EPOR (dimer)	0.011	0.032	-9999	-0.16	9	9
lamellipodium assembly	0.025	0.038	-9999	-0.26	4	4
PIK3CA	0.008	0.048	-9999	-0.38	4	4
PI3K	0.014	0.048	-9999	-0.31	5	5
ARF6	0.014	0	-9999	-10000	0	0
JAK2	-0.004	0.097	-9999	-0.28	23	23
PXN	0.014	0	-9999	-10000	0	0
PIK3R1	0.01	0.037	-9999	-0.42	2	2
MADCAM1	-0.002	0.058	-9999	-0.25	14	14
cell adhesion	-0.013	0.096	-9999	-0.23	38	38
CRKL/CBL	0.02	0.011	-9999	-10000	0	0
ITGB1	0.013	0.016	-9999	-0.25	1	1
SRC	-0.016	0.1	-9999	-0.25	35	35
ITGB7	-0.013	0.1	-9999	-0.41	17	17
RAC1	0.014	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.02	0.11	-9999	-0.29	34	34
p130Cas/Crk/Dock1	0.004	0.09	-9999	-0.34	8	8
VCAM1	-0.022	0.11	-9999	-0.38	24	24
RHOA	0.014	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.01	0.071	-9999	-0.21	23	23
BCAR1	-0.012	0.095	-9999	-0.23	37	37
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	0.039	-9999	-0.27	4	4

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.014	0	-9999	-10000	0	0
GNAT1/GTP	0.003	0.011	-9999	-0.16	1	1
Metarhodopsin II/Arrestin	0.003	0.009	-9999	-0.13	1	1
PDE6G/GNAT1/GTP	-0.015	0.076	-9999	-0.21	33	33
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.004	0.017	-9999	-0.25	1	1
GRK1	0.002	0.005	-9999	-10000	0	0
CNG Channel	-0.046	0.086	-9999	-0.23	35	35
mol:Na +	-0.017	0.07	-9999	-0.25	9	9
mol:ADP	0.002	0.005	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.012	0.088	-9999	-0.25	24	24
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.011	0.075	-9999	-0.25	9	9
CNGB1	0.001	0.041	-9999	-0.25	7	7
RDH5	-0.012	0.087	-9999	-0.28	23	23
SAG	0	0.016	-9999	-0.25	1	1
mol:Ca2+	-0.007	0.071	-9999	-0.29	5	5
Na + (4 Units)	-0.028	0.059	-9999	-0.28	5	5
RGS9	-0.03	0.12	-9999	-0.32	35	35
GNB1/GNGT1	0.002	0.059	-9999	-0.24	14	14
GNAT1/GDP	-0.007	0.075	-9999	-0.21	24	24
GUCY2D	-0.007	0.065	-9999	-0.25	18	18
GNGT1	-0.012	0.084	-9999	-0.36	14	14
GUCY2F	0.001	0.016	-9999	-0.25	1	1
GNB5	0.006	0.055	-9999	-0.39	5	5
mol:GMP (4 units)	-0.02	0.09	-9999	-0.23	33	33
mol:11-cis-retinal	-0.012	0.086	-9999	-0.28	23	23
mol:cGMP	-0.003	0.067	-9999	-0.22	16	16
GNB1	0.014	0	-9999	-10000	0	0
Rhodopsin	-0.005	0.06	-9999	-0.19	23	23
SLC24A1	0.014	0	-9999	-10000	0	0
CNGA1	-0.015	0.084	-9999	-0.27	25	25
Metarhodopsin II	0.004	0.005	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.003	0.07	-9999	-0.24	15	15
RGS9BP	-0.002	0.076	-9999	-0.36	11	11
Metarhodopsin II/Transducin	0.002	0.042	-9999	-0.21	9	9
GCAP Family/Ca ++	-0.001	0.061	-9999	-0.24	14	14
PDE6A/B	-0.009	0.082	-9999	-0.23	31	31
mol:Pi	-0.012	0.088	-9999	-0.25	24	24
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	0.005	0.046	-9999	-0.22	9	9
PDE6B	-0.016	0.11	-9999	-0.39	20	20
PDE6A	0.001	0.052	-9999	-0.25	11	11
PDE6G	-0.032	0.13	-9999	-0.36	33	33
RHO	0.003	0.006	-9999	-10000	0	0
PDE6	-0.034	0.11	-9999	-0.23	53	53
GUCA1A	0.001	0.049	-9999	-0.25	10	10
GC2/GCAP Family	0	0.062	-9999	-0.24	14	14
GUCA1C	0.001	0.016	-9999	-0.25	1	1
GUCA1B	-0.009	0.097	-9999	-0.42	14	14

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.013	0.016	-10000	0	-0.24	1	1
RAS family/GTP	0.003	0.076	-10000	0	-0.28	8	8
NFATC4	-0.005	0.078	0.18	2	-0.25	10	12
ERBB2IP	0.009	0.045	-10000	0	-0.42	3	3
HSP90 (dimer)	0.012	0.026	-10000	0	-0.42	1	1
mammary gland morphogenesis	-0.007	0.082	0.19	3	-0.21	24	27
JUN	0.01	0.075	-10000	0	-0.22	12	12
HRAS	0.013	0.001	-10000	0	-10000	0	0
DOCK7	-0.002	0.079	0.19	3	-0.23	11	14
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.014	0.091	0.22	3	-0.23	31	34
AKT1	0.009	0.002	-10000	0	-10000	0	0
BAD	0.014	0.002	-10000	0	-10000	0	0
MAPK10	-0.007	0.059	-10000	0	-0.16	14	14
mol:GTP	-0.001	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.007	0.087	0.21	3	-0.23	24	27
RAF1	0.004	0.084	-10000	0	-0.29	8	8
ErbB2/ErbB3/neuregulin 2	-0.019	0.099	0.22	2	-0.24	38	40
STAT3	0.016	0.061	-10000	0	-0.97	1	1
cell migration	0.005	0.054	-10000	0	-0.18	5	5
mol:PI-3-4-5-P3	0	0.001	-10000	0	-10000	0	0
cell proliferation	-0.04	0.23	-10000	0	-0.59	36	36
FOS	-0.006	0.14	-10000	0	-0.33	36	36
NRAS	0.013	0.001	-10000	0	-10000	0	0
mol:Ca2+	-0.007	0.082	0.19	3	-0.21	24	27
MAPK3	-0.026	0.18	-10000	0	-0.46	36	36
MAPK1	-0.026	0.18	-10000	0	-0.46	36	36
JAK2	-0.006	0.077	-10000	0	-0.25	8	8
NF2	0.005	0.008	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.009	0.079	-10000	0	-0.24	23	23
NRG1	-0.038	0.12	-10000	0	-0.3	43	43
GRB2/SOS1	0.02	0.001	-10000	0	-10000	0	0
MAPK8	0	0.08	-10000	0	-0.23	23	23
MAPK9	0.009	0.045	-10000	0	-0.15	5	5
ERBB2	-0.007	0.066	0.34	3	-0.3	9	12
ERBB3	-0.005	0.087	-10000	0	-0.42	11	11
SHC1	0.013	0.001	-10000	0	-10000	0	0
RAC1	0.014	0	-10000	0	-10000	0	0
apoptosis	-0.01	0.011	-10000	0	-10000	0	0
STAT3 (dimer)	0.016	0.059	-10000	0	-0.94	1	1
RNF41	0.016	0.015	-10000	0	-0.21	1	1
FRAP1	0.007	0.002	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.02	0.047	-10000	0	-0.22	5	5
ErbB2/ErbB2/HSP90 (dimer)	0.003	0.058	0.23	3	-0.27	9	12
CHRNA1	-0.053	0.24	-10000	0	-0.62	36	36
myelination	-0.004	0.075	0.18	2	-0.26	8	10
PPP3CB	-0.002	0.074	0.18	3	-0.23	9	12
KRAS	0.012	0.016	-10000	0	-0.25	1	1
RAC1-CDC42/GDP	0.007	0.071	-10000	0	-0.24	9	9
NRG2	-0.026	0.12	-10000	0	-0.41	25	25
mol:GDP	-0.009	0.079	-10000	0	-0.24	23	23
SOS1	0.013	0.001	-10000	0	-10000	0	0
MAP2K2	0.004	0.093	-10000	0	-0.34	6	6
SRC	0.012	0.027	-10000	0	-0.42	1	1
mol:cAMP	0	0.001	-10000	0	-10000	0	0
PTPN11	-0.001	0.079	0.19	3	-0.24	9	12
MAP2K1	-0.021	0.16	-10000	0	-0.5	11	11
heart morphogenesis	-0.007	0.082	0.19	3	-0.21	24	27
RAS family/GDP	0.01	0.074	-10000	0	-0.26	8	8
GRB2	0.013	0.001	-10000	0	-10000	0	0
PRKACA	-0.001	0.005	-10000	0	-10000	0	0
CHRNE	0.005	0.035	-10000	0	-0.11	20	20
HSP90AA1	0.012	0.027	-10000	0	-0.42	1	1
activation of caspase activity	-0.009	0.002	-10000	0	-10000	0	0
nervous system development	-0.007	0.082	0.19	3	-0.21	24	27
CDC42	0.014	0	-10000	0	-10000	0	0

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.01	0.037	-9999	-0.42	2	2
SPHK1	-0.008	0.084	-9999	-0.32	17	17
GNAI2	0.014	0	-9999	-10000	0	0
mol:S1P	0.001	0.067	-9999	-0.26	14	14
GNAO1	-0.068	0.17	-9999	-0.41	51	51
mol:Sphinganine-1-P	0.002	0.064	-9999	-0.22	19	19
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.024	0.052	-9999	-0.43	1	1
GNAI3	0.014	0	-9999	-10000	0	0
G12/G13	0.02	0	-9999	-10000	0	0
S1PR3	0.002	0.058	-9999	-0.28	10	10
S1PR2	0.014	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.002	0.057	-9999	-0.23	14	14
S1PR5	-0.003	0.072	-9999	-0.3	14	14
S1PR4	-0.03	0.12	-9999	-0.36	31	31
GNAI1	0.009	0.046	-9999	-0.42	3	3
S1P/S1P5/G12	0.008	0.066	-9999	-0.21	17	17
S1P/S1P3/Gq	0.003	0.081	-9999	-0.28	14	14
S1P/S1P4/Gi	-0.053	0.13	-9999	-0.35	24	24
GNAQ	0.014	0	-9999	-10000	0	0
GNAZ	-0.029	0.12	-9999	-0.39	28	28
GNA14	-0.028	0.1	-9999	-0.27	39	39
GNA15	-0.003	0.081	-9999	-0.39	11	11
GNA12	0.014	0	-9999	-10000	0	0
GNA13	0.014	0	-9999	-10000	0	0
GNA11	0.014	0	-9999	-10000	0	0
ABCC1	0.004	0.064	-9999	-0.42	6	6

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.014	0	-9999	-10000	0	0
VLDLR	-0.005	0.088	-9999	-0.41	12	12
LRPAP1	0.014	0	-9999	-10000	0	0
NUDC	0.014	0	-9999	-10000	0	0
RELN/LRP8	-0.031	0.092	-9999	-0.24	28	28
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	-0.024	0.081	-9999	-0.21	28	28
IQGAP1/CaM	0.02	0	-9999	-10000	0	0
DAB1	-0.02	0.078	-9999	-0.25	28	28
IQGAP1	0.014	0	-9999	-10000	0	0
PLA2G7	-0.034	0.13	-9999	-0.37	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	0.02	0	-9999	-10000	0	0
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.012	0.027	-9999	-0.42	1	1
CDK5R1	0.004	0.064	-9999	-0.42	6	6
LIS1/Poliovirus Protein 3A	0.014	0	-9999	-10000	0	0
CDK5R2	-0.057	0.14	-9999	-0.32	55	55
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.06	0.12	-9999	-0.28	47	47
YWHAE	0.014	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.025	0.092	-9999	-0.28	11	11
MAP1B	-0.004	0.048	-9999	-0.26	9	9
RAC1	0.018	0	-9999	-10000	0	0
p35/CDK5	-0.014	0.082	-9999	-0.19	32	32
RELN	-0.086	0.15	-9999	-0.31	82	82
PAFAH/LIS1	-0.004	0.077	-9999	-0.24	23	23
LIS1/CLIP170	0.023	0.016	-9999	-0.24	1	1
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.033	0.059	-9999	-0.29	4	4
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.026	0.094	-9999	-0.29	15	15
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.033	0.095	-9999	-0.3	11	11
LIS1/IQGAP1	0.024	0	-9999	-10000	0	0
RHOA	0.018	0	-9999	-10000	0	0
PAFAH1B1	0.019	0	-9999	-10000	0	0
PAFAH1B3	0.012	0.027	-9999	-0.42	1	1
PAFAH1B2	0.01	0.037	-9999	-0.42	2	2
MAP1B/LIS1/Dynein heavy chain	0.016	0.032	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.019	0.09	-9999	-0.27	11	11
LRP8	0.014	0	-9999	-10000	0	0
NDEL1/Katanin 60	-0.025	0.092	-9999	-0.28	11	11
P39/CDK5	-0.043	0.092	-9999	-0.19	55	55
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.024	0	-9999	-10000	0	0
CDK5	-0.018	0.075	-9999	-0.19	28	28
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	0.1	-9999	-0.22	47	47
RELN/VLDLR	-0.029	0.1	-9999	-0.24	35	35
CDC42	0.018	0	-9999	-10000	0	0

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.076	0.24	-9999	-0.84	10	10
PCK1	-0.043	0.14	-9999	-0.59	2	2
HNF4A	-0.089	0.25	-9999	-0.89	9	9
KCNJ11	-0.11	0.32	-9999	-0.89	25	25
AKT1	-0.039	0.14	-9999	-0.38	9	9
response to starvation	-0.004	0.012	-9999	-10000	0	0
DLK1	-0.093	0.27	-9999	-0.79	18	18
NKX2-1	-0.01	0.15	-9999	-10000	0	0
ACADM	-0.08	0.25	-9999	-0.84	11	11
TAT	-0.042	0.14	-9999	-0.71	1	1
CEBPB	0.007	0.016	-9999	-10000	0	0
CEBPA	-0.017	0.098	-9999	-0.37	18	18
TTR	-0.24	0.44	-9999	-1.1	48	48
PKLR	-0.2	0.38	-9999	-0.87	53	53
APOA1	-0.087	0.27	-9999	-0.98	9	9
CPT1C	-0.11	0.3	-9999	-0.92	21	21
ALAS1	-0.018	0.14	-9999	-10000	0	0
TFRC	-0.045	0.17	-9999	-0.7	3	3
FOXF1	-0.026	0.11	-9999	-0.29	34	34
NF1	0.015	0.046	-9999	-0.42	3	3
HNF1A (dimer)	0.013	0.028	-9999	-0.42	1	1
CPT1A	-0.086	0.27	-9999	-0.84	16	16
HMGCS1	-0.081	0.25	-9999	-0.79	15	15
NR3C1	0.008	0.06	-9999	-0.42	5	5
CPT1B	-0.088	0.26	-9999	-0.79	18	18
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.013	0.009	-9999	-10000	0	0
GCK	-0.11	0.3	-9999	-0.93	19	19
CREB1	0.013	0.014	-9999	-10000	0	0
IGFBP1	-0.032	0.13	-9999	-0.49	2	2
PDX1	-0.026	0.14	-9999	-10000	0	0
UCP2	-0.089	0.27	-9999	-0.92	14	14
ALDOB	-0.079	0.26	-9999	-0.79	15	15
AFP	-0.03	0.074	-9999	-10000	0	0
BDH1	-0.1	0.3	-9999	-0.88	22	22
HADH	-0.076	0.27	-9999	-0.84	14	14
F2	-0.088	0.27	-9999	-0.98	9	9
HNF1A	0.013	0.028	-9999	-0.42	1	1
G6PC	-0.009	0.068	-9999	-10000	0	0
SLC2A2	-0.036	0.16	-9999	-0.52	2	2
INS	-0.006	0.013	-9999	-10000	0	0
FOXA1	-0.036	0.12	-9999	-0.32	34	34
FOXA3	-0.033	0.11	-9999	-0.28	40	40
FOXA2	-0.089	0.31	-9999	-0.88	16	16
ABCC8	-0.085	0.26	-9999	-0.78	16	16
ALB	-0.028	0.076	-9999	-10000	0	0

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.016	0.005	-10000	0	-10000	0	0
PRKCZ	0.005	0.059	-10000	0	-0.42	5	5
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.014	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.016	0.11	-10000	0	-0.36	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	-0.026	0.1	-10000	0	-0.23	48	48
IL1A	-0.014	0.077	-10000	0	-0.25	26	26
IL1B	-0.04	0.13	-10000	0	-0.27	54	54
IRAK/TRAF6/p62/Atypical PKCs	0.037	0.042	-10000	0	-0.36	1	1
IL1R2	-0.026	0.12	-10000	0	-0.35	29	29
IL1R1	-0.005	0.088	-10000	0	-0.41	12	12
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.007	0.1	0.18	3	-0.35	14	17
TOLLIP	0.014	0	-10000	0	-10000	0	0
TICAM2	0.002	0.069	-10000	0	-0.42	7	7
MAP3K3	0.014	0	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.008	0.016	-10000	0	-0.25	1	1
IKK complex/ELKS	0.05	0.028	-10000	0	-0.32	1	1
JUN	0.023	0.04	-10000	0	-10000	0	0
MAP3K7	0.012	0.027	-10000	0	-0.42	1	1
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.021	0.13	-10000	0	-0.45	13	13
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.002	0.078	-10000	0	-0.22	21	21
PIK3R1	0.01	0.037	-10000	0	-0.42	2	2
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.004	0.078	-10000	0	-0.21	21	21
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	0.042	-10000	0	-0.17	10	10
IRAK1	0.02	0.003	-10000	0	-10000	0	0
IL1RN/IL1R1	-0.009	0.089	-10000	0	-0.3	19	19
IRAK4	0.011	0.031	-10000	0	-0.33	2	2
PRKCI	0.009	0.046	-10000	0	-0.42	3	3
TRAF6	0.014	0	-10000	0	-10000	0	0
PI3K	0.014	0.048	-10000	0	-0.31	5	5
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.018	0.12	-10000	0	-0.41	15	15
CHUK	0.012	0.027	-10000	0	-0.42	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.035	0.13	-10000	0	-0.27	47	47
IL1 beta/IL1R2	-0.048	0.13	-10000	0	-0.3	49	49
IRAK/TRAF6/TAK1/TAB1/TAB2	0.028	0.013	-10000	0	-0.18	1	1
NF kappa B1 p50/RelA	-0.047	0.1	-10000	0	-0.43	12	12
IRAK3	0	0.071	-10000	0	-0.35	10	10
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.024	0.13	-10000	0	-0.46	14	14
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.004	0.07	-10000	0	-0.22	20	20
IL1 alpha/IL1R1/IL1RAP	-0.011	0.084	-10000	0	-0.25	20	20
RELA	0.014	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.012	0.027	-10000	0	-0.42	1	1
MYD88	0.012	0.027	-10000	0	-0.42	1	1
IRAK/TRAF6/MEKK3	0.034	0.003	-10000	0	-10000	0	0
IL1RAP	-0.006	0.085	-10000	0	-0.36	14	14
UBE2N	0.014	0	-10000	0	-10000	0	0
IRAK/TRAF6	-0.044	0.098	-10000	0	-0.38	14	14
CASP1	-0.014	0.1	-10000	0	-0.39	18	18
IL1RN/IL1R2	-0.024	0.1	-10000	0	-0.24	45	45
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.025	0.13	-10000	0	-0.26	47	47
TMEM189-UBE2V1	0.008	0.007	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.009	0.079	-10000	0	-0.3	13	13
PIK3CA	0.008	0.048	-10000	0	-0.38	4	4
IL1RN	-0.01	0.09	-10000	0	-0.33	18	18
TRAF6/TAK1/TAB1/TAB2	0.023	0.014	-10000	0	-0.19	1	1
MAP2K6	0.019	0.039	-10000	0	-0.18	10	10

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.01	0.037	-9999	-0.42	2	2
mol:S1P	0.001	0.002	-9999	-10000	0	0
S1P1/S1P/Gi	-0.031	0.1	-9999	-0.2	67	67
GNAO1	-0.066	0.17	-9999	-0.41	51	51
S1P/S1P3/G12/G13	0.023	0.031	-9999	-0.21	2	2
AKT1	0	0.063	-9999	-0.49	2	2
AKT3	-0.001	0.096	-9999	-1.1	1	1
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.01	0.037	-9999	-0.42	2	2
GNAI2	0.015	0.002	-9999	-10000	0	0
GNAI3	0.015	0.002	-9999	-10000	0	0
GNAI1	0.01	0.046	-9999	-0.42	3	3
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.004	0.058	-9999	-0.28	10	10
S1PR2	0.014	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	-0.028	0.11	-9999	-0.22	51	51
MAPK3	-0.022	0.1	-9999	-0.33	10	10
MAPK1	-0.022	0.1	-9999	-0.33	10	10
JAK2	-0.027	0.11	-9999	-0.32	12	12
CXCR4	-0.029	0.11	-9999	-0.33	12	12
FLT1	0.013	0.031	-9999	-0.33	2	2
RhoA/GDP	0.01	0	-9999	-10000	0	0
Rac1/GDP	0.01	0	-9999	-10000	0	0
SRC	-0.023	0.1	-9999	-0.33	10	10
S1P/S1P3/Gi	-0.028	0.11	-9999	-0.22	51	51
RAC1	0.014	0	-9999	-10000	0	0
RhoA/GTP	-0.02	0.1	-9999	-0.32	10	10
VEGFA	0.006	0.052	-9999	-0.26	9	9
S1P/S1P2/Gi	-0.027	0.11	-9999	-0.22	48	48
VEGFR1 homodimer/VEGFA homodimer	0.018	0.044	-9999	-0.2	10	10
RHOA	0.014	0	-9999	-10000	0	0
S1P/S1P3/Gq	0.002	0.067	-9999	-0.24	14	14
GNAQ	0.014	0	-9999	-10000	0	0
GNAZ	-0.028	0.13	-9999	-0.39	28	28
G12/G13	0.02	0	-9999	-10000	0	0
GNA14	-0.028	0.1	-9999	-0.27	39	39
GNA15	-0.003	0.081	-9999	-0.39	11	11
GNA12	0.014	0	-9999	-10000	0	0
GNA13	0.014	0	-9999	-10000	0	0
GNA11	0.014	0	-9999	-10000	0	0
Rac1/GTP	-0.02	0.1	-9999	-0.32	10	10

×

Cellular roles of Anthrax toxin

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
ANTXR1	-0.003	0.082	-10000	0	-0.42	10	10
ANTXR2	0	0.07	-10000	0	-0.33	11	11
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.004	0.013	-10000	0	-0.056	15	15
monocyte activation	-0.039	0.15	-10000	0	-0.46	28	28
MAP2K2	0.009	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	-0.003	0.042	-10000	0	-0.22	9	9
CYAA	-0.004	0.052	-10000	0	-0.2	15	15
MAP2K4	0.005	0.013	-10000	0	-10000	0	0
IL1B	-0.028	0.087	-10000	0	-0.18	48	48
Channel	0.001	0.057	-10000	0	-0.22	15	15
NLRP1	-0.004	0.045	-10000	0	-0.18	14	14
CALM1	0.014	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	0.007	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	0.056	15	-10000	0	15
MAPK3	0.005	0.013	-10000	0	-10000	0	0
MAPK1	0.005	0.013	-10000	0	-10000	0	0
PGR	-0.007	0.045	-10000	0	-0.16	17	17
PA/Cellular Receptors	0.001	0.063	-10000	0	-0.24	15	15
apoptosis	-0.004	0.013	-10000	0	-0.056	15	15
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.002	0.054	-10000	0	-0.21	15	15
macrophage activation	0.01	0.013	-10000	0	-10000	0	0
TNF	-0.025	0.11	-10000	0	-0.34	29	29
VCAM1	-0.039	0.15	-10000	0	-0.46	28	28
platelet activation	0.007	0.017	-10000	0	-10000	0	0
MAPKKK cascade	-0.006	0.018	0.092	2	-10000	0	2
IL18	-0.02	0.087	-10000	0	-0.23	30	30
negative regulation of macrophage activation	-0.004	0.013	-10000	0	-0.056	15	15
LEF	-0.004	0.013	-10000	0	-0.056	15	15
CASP1	-0.006	0.046	-10000	0	-0.13	19	19
mol:cAMP	0.007	0.017	-10000	0	-10000	0	0
necrosis	-0.004	0.013	-10000	0	-0.056	15	15
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.002	0.054	-10000	0	-0.2	15	15
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.013	0.016	-10000	0	-0.25	1	1
Rac1/GDP	0.011	0.01	-10000	0	-10000	0	0
DOCK1	0.014	0	-10000	0	-10000	0	0
ITGA4	-0.031	0.13	-10000	0	-0.38	30	30
RAC1	0.014	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	-0.03	0.12	-10000	0	-0.29	43	43
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.014	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.001	0.077	-10000	0	-0.24	23	23
alpha4/beta7 Integrin/Paxillin	-0.007	0.092	-10000	0	-0.22	37	37
lamellipodium assembly	0.033	0.056	-10000	0	-0.38	4	4
PIK3CA	0.008	0.048	-10000	0	-0.38	4	4
PI3K	0.014	0.048	-10000	0	-0.31	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	-0.42	2	2
ARF6/GTP	0.014	0.059	-10000	0	-0.17	23	23
cell adhesion	0.014	0.066	-10000	0	-0.19	23	23
CRKL/CBL	0.02	0.011	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.007	0.07	-10000	0	-0.21	23	23
ITGB1	0.013	0.016	-10000	0	-0.25	1	1
ITGB7	-0.013	0.1	-10000	0	-0.41	17	17
ARF6/GDP	0.011	0.01	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.003	0.098	-10000	0	-0.23	34	34
p130Cas/Crk/Dock1	0.026	0.023	-10000	0	-0.24	2	2
VCAM1	-0.022	0.11	-10000	0	-0.38	24	24
alpha4/beta1 Integrin/Paxillin/Talin	0.015	0.066	-10000	0	-0.19	23	23
alpha4/beta1 Integrin/Paxillin/GIT1	0.015	0.066	-10000	0	-0.19	23	23
BCAR1	0.01	0.037	-10000	0	-0.42	2	2
mol:GDP	-0.014	0.066	0.19	23	-10000	0	23
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	0.015	0.066	-10000	0	-0.19	23	23
Rac1/GTP	0.034	0.061	-10000	0	-0.42	4	4

×

Regulation of p38-alpha and p38-beta

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.019	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	-0.42	9	9
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.014	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.016	0.017	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
YES1	0.007	0.053	-9999	-0.42	4	4
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.014	0	-9999	-10000	0	0
FYN	0.014	0	-9999	-10000	0	0
MAP3K12	0.014	0	-9999	-10000	0	0
FGR	-0.008	0.091	-9999	-0.37	15	15
p38 alpha/TAB1	-0.046	0.094	-9999	-0.27	31	31
PRKG1	-0.02	0.11	-9999	-0.36	24	24
DUSP8	-0.012	0.094	-9999	-0.34	19	19
PGK/cGMP/p38 alpha	-0.051	0.098	-9999	-0.27	35	35
apoptosis	-0.044	0.09	-9999	-0.26	31	31
RAL/GTP	0.019	0	-9999	-10000	0	0
LYN	0.009	0.046	-9999	-0.42	3	3
DUSP1	0.007	0.044	-9999	-0.28	6	6
PAK1	0.012	0.023	-9999	-0.25	2	2
SRC	0.012	0.027	-9999	-0.42	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	0.019	0	-9999	-10000	0	0
MAPK11	-0.033	0.14	-9999	-0.33	36	36
BLK	-0.082	0.16	-9999	-0.33	74	74
HCK	-0.011	0.1	-9999	-0.42	15	15
MAP2K3	0.014	0	-9999	-10000	0	0
DUSP16	0.014	0	-9999	-10000	0	0
DUSP10	0.001	0.074	-9999	-0.42	8	8
TRAF6/MEKK3	0.018	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	-0.02	0.12	-9999	-0.3	30	30
positive regulation of innate immune response	-0.032	0.15	-9999	-0.38	32	32
LCK	-0.067	0.16	-9999	-0.37	56	56
p38alpha-beta/MKP7	-0.024	0.15	-9999	-0.36	32	32
p38alpha-beta/MKP5	-0.028	0.15	-9999	-0.38	33	33
PGK/cGMP	-0.013	0.076	-9999	-0.25	24	24
PAK2	0.014	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.025	0.15	-9999	-0.36	32	32
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	-0.015	0.077	-9999	-0.25	26	26

×

Nongenotropic Androgen 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
PTK2	0.009	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.003	0.071	-10000	0	-0.21	21	21
regulation of S phase of mitotic cell cycle	0.007	0.06	-10000	0	-0.21	16	16
GNAO1	-0.068	0.17	-10000	0	-0.41	51	51
HRAS	0.014	0	-10000	0	-10000	0	0
SHBG/T-DHT	0.003	0.035	-10000	0	-0.2	7	7
PELP1	0.014	0	-10000	0	-10000	0	0
AKT1	0.009	0	-10000	0	-10000	0	0
MAP2K1	0.019	0.048	-10000	0	-0.2	1	1
T-DHT/AR	-0.016	0.073	-10000	0	-0.21	30	30
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	0.009	0.046	-10000	0	-0.42	3	3
mol:GDP	-0.022	0.073	-10000	0	-0.34	12	12
cell proliferation	0.026	0.052	-10000	0	-10000	0	0
PIK3CA	0.008	0.048	-10000	0	-0.38	4	4
FOS	0.03	0.043	-10000	0	-10000	0	0
mol:Ca2+	-0.009	0.027	-10000	0	-0.052	68	68
MAPK3	0.022	0.05	-10000	0	-0.22	1	1
MAPK1	0.019	0.026	-10000	0	-10000	0	0
PIK3R1	0.01	0.037	-10000	0	-0.42	2	2
mol:IP3	0	0	-10000	0	-0.002	6	6
cAMP biosynthetic process	0.004	0.036	0.093	1	-0.18	6	7
GNG2	-0.003	0.082	-10000	0	-0.42	10	10
potassium channel inhibitor activity	0	0	-10000	0	-0.002	6	6
HRAS/GTP	0.01	0.052	-10000	0	-0.18	12	12
actin cytoskeleton reorganization	0.017	0.033	-10000	0	-0.23	4	4
SRC	0.012	0.027	-10000	0	-0.42	1	1
voltage-gated calcium channel activity	0	0	-10000	0	-0.002	6	6
PI3K	0.013	0.041	-10000	0	-0.26	5	5
apoptosis	-0.028	0.039	-10000	0	-10000	0	0
T-DHT/AR/PELP1	-0.003	0.062	-10000	0	-0.24	11	11
HRAS/GDP	0.002	0.075	-10000	0	-0.32	12	12
CREB1	0.028	0.041	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0.022	0.034	-10000	0	-0.23	4	4
AR	-0.024	0.11	-10000	0	-0.31	30	30
GNB1	0.014	0	-10000	0	-10000	0	0
RAF1	0.014	0.05	-10000	0	-0.17	12	12
RAC1-CDC42/GDP	0.009	0.073	-10000	0	-0.3	12	12
T-DHT/AR/PELP1/Src	0.006	0.059	-10000	0	-0.21	12	12
MAP2K2	0.019	0.048	-10000	0	-0.2	1	1
T-DHT/AR/PELP1/Src/PI3K	0.007	0.06	-10000	0	-0.21	16	16
GNAZ	-0.029	0.12	-10000	0	-0.39	28	28
SHBG	0.004	0.059	-10000	0	-0.35	7	7
Gi family/GNB1/GNG2/GDP	-0.048	0.14	-10000	0	-0.3	49	49
mol:T-DHT	0	0	-10000	0	-10000	0	0
RAC1	0.014	0	-10000	0	-10000	0	0
GNRH1	-0.002	0.056	-10000	0	-0.28	10	10
Gi family/GTP	-0.037	0.1	-10000	0	-0.19	68	68
CDC42	0.014	0	-10000	0	-10000	0	0

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	-0.006	0.069	-10000	0	-0.2	22	22
GRB2/SOS1/SHC	0.028	0	-10000	0	-10000	0	0
HRAS	0.014	0	-10000	0	-10000	0	0
IRS1/Crk	-0.003	0.069	-10000	0	-0.2	22	22
IGF-1R heterotetramer/IGF1/PTP1B	0.002	0.071	-10000	0	-0.22	22	22
AKT1	0.006	0.069	-10000	0	-0.32	4	4
BAD	0.01	0.065	-10000	0	-0.3	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.005	0.069	-10000	0	-0.2	22	22
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.003	0.07	-10000	0	-0.21	22	22
RAF1	0.016	0.063	-10000	0	-0.29	3	3
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.008	0.068	-10000	0	-0.19	21	21
YWHAZ	0.014	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.01	0.076	-10000	0	-0.2	34	34
PIK3CA	0.008	0.048	-10000	0	-0.38	4	4
RPS6KB1	0.006	0.069	-10000	0	-0.32	4	4
GNB2L1	0.014	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	0.012	0.056	-10000	0	-0.26	3	3
PXN	0.014	0	-10000	0	-10000	0	0
PIK3R1	0.01	0.037	-10000	0	-0.42	2	2
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.02	0	-10000	0	-10000	0	0
HRAS/GTP	-0.018	0.048	-10000	0	-0.31	1	1
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.021	0.057	-10000	0	-0.21	1	1
IGF-1R heterotetramer	0.003	0.045	-10000	0	-0.37	3	3
IGF-1R heterotetramer/IGF1/IRS/Nck	0	0.071	-10000	0	-0.21	22	22
Crk/p130 Cas/Paxillin	0.01	0.068	-10000	0	-0.18	23	23
IGF1R	0.003	0.045	-10000	0	-0.37	3	3
IGF1	-0.026	0.12	-10000	0	-0.39	25	25
IRS2/Crk	0.002	0.067	-10000	0	-0.19	23	23
PI3K	0.003	0.078	-10000	0	-0.21	25	25
apoptosis	-0.017	0.06	0.26	4	-10000	0	4
HRAS/GDP	0.01	0	-10000	0	-10000	0	0
PRKCD	0.002	0.09	-10000	0	-0.29	22	22
RAF1/14-3-3 E	0.023	0.058	-10000	0	-0.25	3	3
BAD/14-3-3	0.017	0.063	-10000	0	-0.27	4	4
PRKCZ	0.002	0.073	-10000	0	-0.24	9	9
Crk/p130 Cas/Paxillin/FAK1	-0.018	0.049	-10000	0	-0.25	5	5
PTPN1	0.013	0.016	-10000	0	-0.25	1	1
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.003	0.094	-10000	0	-0.31	21	21
BCAR1	0.01	0.037	-10000	0	-0.42	2	2
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.009	0.068	-10000	0	-0.19	25	25
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.014	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.003	0.069	-10000	0	-0.2	22	22
GRB10	0.007	0.053	-10000	0	-0.42	4	4
PTPN11	-0.005	0.069	-10000	0	-0.2	22	22
IRS1	-0.006	0.069	-10000	0	-0.23	22	22
IRS2	-0.006	0.07	-10000	0	-0.2	23	23
IGF-1R heterotetramer/IGF1	-0.014	0.092	-10000	0	-0.27	28	28
GRB2	0.014	0	-10000	0	-10000	0	0
PDPK1	0.002	0.072	-10000	0	-0.2	24	24
YWHAE	0.014	0	-10000	0	-10000	0	0
PRKD1	0.002	0.089	-10000	0	-0.29	21	21
SHC1	0.014	0	-10000	0	-10000	0	0

×

Regulation of nuclear SMAD2/3 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
EP300	0.016	0.012	-10000	0	-10000	0	0
HSPA8	0.013	0.003	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	0.017	0.075	0.19	5	-0.25	12	17
AKT1	0.002	0.029	-10000	0	-10000	0	0
GSC	-0.028	0.23	-10000	0	-1.3	8	8
NKX2-5	-0.12	0.17	-10000	0	-0.32	99	99
muscle cell differentiation	0.018	0.074	0.32	5	-10000	0	5
SMAD2-3/SMAD4/SP1	0.027	0.087	-10000	0	-0.25	4	4
SMAD4	0.009	0.034	-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	-0.008	0.095	-10000	0	-0.23	35	35
SMAD3/SMAD4/VDR	0.044	0.05	-10000	0	-0.25	4	4
MYC	0.023	0.032	-10000	0	-0.25	1	1
CDKN2B	-0.17	0.46	-10000	0	-1.3	39	39
AP1	0.035	0.044	-10000	0	-0.3	1	1
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.037	0.043	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.023	0.12	-10000	0	-0.29	40	40
SP3	0.012	0.038	-10000	0	-0.42	2	2
CREB1	0.014	0	-10000	0	-10000	0	0
FOXH1	0.007	0.045	-10000	0	-0.36	3	3
SMAD3/SMAD4/GR	0.023	0.061	-10000	0	-0.25	7	7
GATA3	-0.061	0.17	-10000	0	-0.41	47	47
SKI/SIN3/HDAC complex/NCoR1	0.037	0.014	-10000	0	-10000	0	0
MEF2C/TIF2	-0.039	0.12	-10000	0	-0.45	9	9
endothelial cell migration	0.03	0.23	1.3	9	-10000	0	9
MAX	0.014	0.01	-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	0.073	-10000	0	-0.38	9	9
RUNX3	-0.035	0.14	-10000	0	-0.42	30	30
RUNX1	0.005	0.059	-10000	0	-0.42	5	5
CTBP1	0.014	0	-10000	0	-10000	0	0
NR3C1	0.006	0.06	-10000	0	-0.42	5	5
VDR	0.004	0.064	-10000	0	-0.42	6	6
CDKN1A	0.008	0.17	-10000	0	-1.2	5	5
KAT2B	0.001	0.074	-10000	0	-0.42	8	8
SMAD2/SMAD2/SMAD4/FOXH1	0.017	0.066	-10000	0	-0.23	10	10
DCP1A	0.014	0	-10000	0	-10000	0	0
SKI	0.013	0.001	-10000	0	-10000	0	0
SERPINE1	-0.034	0.24	-10000	0	-1.3	9	9
SMAD3/SMAD4/ATF2	0.023	0.052	-10000	0	-0.23	5	5
SMAD3/SMAD4/ATF3	0.023	0.05	-10000	0	-0.23	3	3
SAP30	0.012	0.016	-10000	0	-0.25	1	1
Cbp/p300/PIAS3	0.036	0.028	0.18	1	-10000	0	1
JUN	0.03	0.043	-10000	0	-0.3	1	1
SMAD3/SMAD4/IRF7	0.02	0.063	-10000	0	-0.25	8	8
TFE3	0.016	0.013	-10000	0	-10000	0	0
COL1A2	-0.03	0.16	-10000	0	-0.8	10	10
mesenchymal cell differentiation	-0.017	0.066	0.27	9	-10000	0	9
DLX1	-0.066	0.15	-10000	0	-0.34	60	60
TCF3	0.014	0	-10000	0	-10000	0	0
FOS	0.009	0.045	-10000	0	-0.25	8	8
SMAD3/SMAD4/Max	0.029	0.047	-10000	0	-0.2	2	2
Cbp/p300/SNIP1	0.03	0.01	-10000	0	-10000	0	0
ZBTB17	0.022	0.021	-10000	0	-10000	0	0
LAMC1	0.031	0.039	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.025	0.046	-10000	0	-0.22	3	3
IRF7	0.003	0.068	-10000	0	-0.38	8	8
ESR1	-0.004	0.087	-10000	0	-0.39	12	12
HNF4A	-0.003	0.049	-10000	0	-0.25	10	10
MEF2C	-0.043	0.11	-10000	0	-0.42	9	9
SMAD2-3/SMAD4	0.018	0.064	-10000	0	-0.24	3	3
Cbp/p300/Src-1	0.032	0.017	-10000	0	-10000	0	0
IGHV3OR16-13	-0.006	0.019	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.012	0.026	-10000	0	-0.42	1	1
CREBBP	0.016	0.008	-10000	0	-10000	0	0
SKIL	-0.001	0.078	-10000	0	-0.42	9	9
HDAC1	0.012	0.027	-10000	0	-0.42	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	0.036	0.047	-10000	0	-0.21	2	2
MSG1/HSC70	-0.029	0.11	-10000	0	-0.25	48	48
SMAD2	0.001	0.035	-10000	0	-10000	0	0
SMAD3	0.009	0.047	-10000	0	-0.4	2	2
SMAD3/E2F4-5/DP1/p107/SMAD4	0.023	0.053	-10000	0	-0.21	6	6
SMAD2/SMAD2/SMAD4	0.002	0.053	-10000	0	-0.28	8	8
NCOR1	0.013	0.001	-10000	0	-10000	0	0
NCOA2	0.003	0.066	-10000	0	-0.4	7	7
NCOA1	0.014	0	-10000	0	-10000	0	0
MYOD/E2A	0.009	0.035	-10000	0	-0.16	11	11
SMAD2-3/SMAD4/SP1/MIZ-1	0.033	0.085	-10000	0	-0.24	3	3
IFNB1	0.015	0.054	-10000	0	-0.25	4	4
SMAD3/SMAD4/MEF2C	-0.033	0.12	-10000	0	-0.4	10	10
CITED1	-0.055	0.15	-10000	0	-0.37	48	48
SMAD2-3/SMAD4/ARC105	0.028	0.058	-10000	0	-0.26	1	1
RBL1	0.01	0.037	-10000	0	-0.42	2	2
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.034	0.18	-10000	0	-0.46	40	40
RUNX1-3/PEBPB2	-0.007	0.091	-10000	0	-0.24	34	34
SMAD7	0.042	0.076	-10000	0	-0.65	1	1
MYC/MIZ-1	0.038	0.051	0.16	39	-0.16	1	40
SMAD3/SMAD4	0.028	0.1	0.3	5	-0.41	7	12
IL10	-0.033	0.17	-10000	0	-0.47	26	26
PIASy/HDAC complex	0.011	0.009	-10000	0	-10000	0	0
PIAS3	0.014	0.004	-10000	0	-10000	0	0
CDK2	0.002	0.074	-10000	0	-0.42	8	8
IL5	-0.025	0.13	-10000	0	-0.33	28	28
CDK4	0.013	0.03	-10000	0	-0.25	3	3
PIAS4	0.011	0.009	-10000	0	-10000	0	0
ATF3	0.008	0.041	-10000	0	-0.28	5	5
SMAD3/SMAD4/SP1	0.026	0.069	-10000	0	-0.22	4	4
FOXG1	-0.04	0.12	-10000	0	-0.3	41	41
FOXO3	0.005	0.037	-10000	0	-10000	0	0
FOXO1	0.004	0.041	-10000	0	-0.29	1	1
FOXO4	0.005	0.037	-10000	0	-10000	0	0
heart looping	-0.043	0.11	-10000	0	-0.42	9	9
CEBPB	0.008	0.016	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.024	0.1	-10000	0	-0.23	42	42
MYOD1	-0.003	0.051	-10000	0	-0.25	11	11
SMAD3/SMAD4/HNF4	0.015	0.051	-10000	0	-0.22	2	2
SMAD3/SMAD4/GATA3	-0.024	0.14	-10000	0	-0.33	41	41
SnoN/SIN3/HDAC complex/NCoR1	-0.001	0.078	-10000	0	-0.42	9	9
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.01	0.092	-10000	0	-0.24	17	17
SMAD3/SMAD4/SP1-3	0.038	0.069	-10000	0	-0.23	1	1
MED15	0.014	0	-10000	0	-10000	0	0
SP1	0.007	0.033	-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	-0.043	0.12	-10000	0	-0.3	16	16
ITGB5	0.026	0.065	-10000	0	-0.4	2	2
TGIF/SIN3/HDAC complex/CtBP	0.037	0.018	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	0.003	0.081	-10000	0	-0.26	14	14
AR	-0.024	0.11	-10000	0	-0.31	30	30
negative regulation of cell growth	0.026	0.054	-10000	0	-0.27	2	2
SMAD3/SMAD4/MYOD	0.015	0.053	-10000	0	-0.2	4	4
E2F5	0	0.076	-10000	0	-0.4	9	9
E2F4	0.014	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.036	0.051	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4	-0.014	0.13	-10000	0	-0.31	40	40
TFDP1	0.014	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.041	0.048	-10000	0	-0.3	1	1
SMAD3/SMAD4/RUNX2	0.018	0.067	-10000	0	-0.27	9	9
TGIF2	0.012	0.027	-10000	0	-0.42	1	1
TGIF1	0.012	0.027	-10000	0	-0.42	1	1
ATF2	0.009	0.046	-10000	0	-0.42	3	3

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.003	0.065	-9999	-0.42	6	6
SVIL	0.008	0.046	-9999	-0.42	3	3
ZNF318	0.015	0.007	-9999	-10000	0	0
JMJD2C	-0.003	0.022	-9999	-0.072	15	15
T-DHT/AR/Ubc9	-0.02	0.08	-9999	-0.23	24	24
CARM1	0.014	0	-9999	-10000	0	0
PRDX1	0.009	0.046	-9999	-0.42	3	3
PELP1	0.014	0.001	-9999	-10000	0	0
CTNNB1	0.013	0.002	-9999	-10000	0	0
AKT1	0.014	0.002	-9999	-10000	0	0
PTK2B	0.009	0.038	-9999	-0.29	4	4
MED1	0.014	0.002	-9999	-10000	0	0
MAK	0.011	0.038	-9999	-0.42	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	-0.42	1	1
NCOA2	0.003	0.066	-9999	-0.4	7	7
NCOA6	0.013	0.003	-9999	-10000	0	0
DNA-PK	0.029	0.007	-9999	-10000	0	0
NCOA4	0.014	0	-9999	-10000	0	0
PIAS3	0.013	0.002	-9999	-10000	0	0
cell proliferation	-0.014	0.053	-9999	-0.56	2	2
XRCC5	0.014	0.001	-9999	-10000	0	0
UBE3A	0.013	0.005	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.033	0.095	-9999	-0.24	35	35
FHL2	-0.033	0.2	-9999	-0.89	13	13
RANBP9	0.013	0.003	-9999	-10000	0	0
JMJD1A	-0.016	0.052	-9999	-0.13	40	40
CDK6	0.001	0.074	-9999	-0.42	8	8
TGFB1I1	0.004	0.061	-9999	-0.39	6	6
T-DHT/AR/CyclinD1	-0.026	0.086	-9999	-0.23	29	29
XRCC6	0.014	0.001	-9999	-10000	0	0
T-DHT/AR	-0.031	0.12	-9999	-0.26	34	34
CTDSP1	0.013	0.001	-9999	-10000	0	0
CTDSP2	0.014	0.005	-9999	-10000	0	0
BRCA1	0.01	0.038	-9999	-0.42	2	2
TCF4	-0.003	0.073	-9999	-0.29	15	15
CDKN2A	-0.13	0.19	-9999	-0.37	100	100
SRF	0.014	0.03	-9999	-10000	0	0
NKX3-1	-0.1	0.28	-9999	-0.84	29	29
KLK3	0.003	0.053	-9999	-10000	0	0
TMF1	0.004	0.064	-9999	-0.42	6	6
HNRNPA1	0.014	0.003	-9999	-10000	0	0
AOF2	0	0.003	-9999	-10000	0	0
APPL1	0.019	0.004	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.021	0.082	-9999	-0.24	23	23
AR	-0.038	0.11	-9999	-0.33	30	30
UBA3	0.012	0.027	-9999	-0.42	1	1
PATZ1	0.014	0.003	-9999	-10000	0	0
PAWR	-0.033	0.13	-9999	-0.41	29	29
PRKDC	0.014	0.001	-9999	-10000	0	0
PA2G4	0.014	0.003	-9999	-10000	0	0
UBE2I	0.014	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.017	0.073	-9999	-0.21	23	23
RPS6KA3	0.011	0.027	-9999	-0.42	1	1
T-DHT/AR/ARA70	-0.02	0.08	-9999	-0.23	23	23
LATS2	0.014	0.002	-9999	-10000	0	0
T-DHT/AR/PRX1	-0.019	0.079	-9999	-0.22	24	24
Cyclin D3/CDK11 p58	0.01	0	-9999	-10000	0	0
VAV3	-0.018	0.099	-9999	-0.31	26	26
KLK2	-0.038	0.13	-9999	-0.91	4	4
CASP8	0.012	0.026	-9999	-0.41	1	1
T-DHT/AR/TIF2/CARM1	-0.014	0.082	-9999	-0.22	25	25
TMPRSS2	-0.067	0.2	-9999	-0.67	18	18
CCND1	0.004	0.059	-9999	-0.35	7	7
PIAS1	0.013	0.005	-9999	-10000	0	0
mol:T-DHT	-0.014	0.031	-9999	-0.068	55	55
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.012	0.007	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.028	0.092	-9999	-0.24	30	30
CMTM2	0.008	0.032	-9999	-0.25	4	4
SNURF	-0.008	0.093	-9999	-0.42	13	13
ZMIZ1	0	0.03	-9999	-10000	0	0
CCND3	0.014	0	-9999	-10000	0	0
TGIF1	0.012	0.026	-9999	-0.41	1	1
FKBP4	0.013	0.003	-9999	-10000	0	0

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.017	0.038	-10000	0	-10000	0	0
epithelial cell differentiation	-0.031	0.062	-10000	0	-0.33	2	2
ITCH	0.017	0.009	-10000	0	-10000	0	0
WWP1	0.018	0.032	-10000	0	-10000	0	0
FYN	0.014	0	-10000	0	-10000	0	0
EGFR	-0.021	0.1	-10000	0	-0.29	30	30
PRL	-0.012	0.066	-10000	0	-0.25	19	19
neuron projection morphogenesis	0.02	0.058	-10000	0	-10000	0	0
PTPRZ1	-0.064	0.16	-10000	0	-0.38	52	52
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.016	0.064	-10000	0	-10000	0	0
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.004	0.068	-10000	0	-0.3	2	2
ADAM17	0.017	0.009	-10000	0	-10000	0	0
ErbB4/ErbB4	0.015	0.042	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.071	0.12	-10000	0	-0.34	7	7
NCOR1	0.014	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	0.004	0.065	-10000	0	-0.28	2	2
GRIN2B	-0.002	0.068	-10000	0	-0.27	3	3
ErbB4/ErbB2/betacellulin	0.005	0.058	-10000	0	-0.28	1	1
STAT1	0.01	0.037	-10000	0	-0.42	2	2
HBEGF	0.011	0.028	-10000	0	-0.25	3	3
PRLR	-0.068	0.15	-10000	0	-0.31	66	66
E4ICDs/ETO2	0	0.066	-10000	0	-0.34	1	1
axon guidance	0.031	0.062	-10000	0	-10000	0	0
NEDD4	0.012	0.047	-10000	0	-0.42	3	3
Prolactin receptor/Prolactin receptor/Prolactin	-0.053	0.11	-10000	0	-0.21	80	80
CBFA2T3	-0.021	0.1	-10000	0	-0.31	29	29
ErbB4/ErbB2/HBEGF	0.02	0.048	-10000	0	-0.28	1	1
MAPK3	0.016	0.06	-10000	0	-10000	0	0
STAT1 (dimer)	0.017	0.041	-10000	0	-10000	0	0
MAPK1	0.016	0.06	-10000	0	-10000	0	0
JAK2	0.004	0.061	-10000	0	-0.39	6	6
ErbB4/ErbB2/neuregulin 1 beta	-0.005	0.074	-10000	0	-0.28	4	4
NRG1	-0.015	0.083	-10000	0	-0.2	41	41
NRG3	-0.15	0.2	-10000	0	-0.37	112	112
NRG2	-0.026	0.12	-10000	0	-0.41	25	25
NRG4	0.006	0.036	-10000	0	-0.25	5	5
heart development	0.031	0.062	-10000	0	-10000	0	0
neural crest cell migration	-0.005	0.074	-10000	0	-0.28	4	4
ERBB2	0.01	0.057	-10000	0	-0.29	9	9
WWOX/E4ICDs	0.019	0.036	-10000	0	-10000	0	0
SHC1	0.014	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	0.005	0.062	-10000	0	-10000	0	0
apoptosis	0.097	0.17	0.34	80	-10000	0	80
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.003	0.081	-10000	0	-0.34	4	4
ErbB4/ErbB2/epiregulin	0.001	0.073	-10000	0	-0.32	5	5
ErbB4/ErbB4/betacellulin/betacellulin	0.002	0.052	-10000	0	-10000	0	0
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.016	0.094	-10000	0	-0.34	8	8
MDM2	0.017	0.038	-10000	0	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	0.002	0.063	-10000	0	-0.26	2	2
STAT5A	0.034	0.06	-10000	0	-0.28	1	1
ErbB4/EGFR/neuregulin 1 beta	-0.012	0.084	-10000	0	-0.28	4	4
DLG4	0.009	0.041	-10000	0	-0.36	3	3
GRB2/SHC	0.02	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	0.017	0.032	-10000	0	-10000	0	0
STAT5A (dimer)	-0.021	0.073	-10000	0	-0.36	2	2
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.036	0.055	-10000	0	-10000	0	0
LRIG1	0.005	0.049	-10000	0	-0.27	8	8
EREG	-0.027	0.1	-10000	0	-0.28	33	33
BTC	-0.018	0.08	-10000	0	-0.26	25	25
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.031	0.062	-10000	0	-10000	0	0
ERBB4	0.015	0.042	-10000	0	-10000	0	0
STAT5B	0.014	0	-10000	0	-10000	0	0
YAP1	0.014	0.009	-10000	0	-10000	0	0
GRB2	0.014	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0.017	0.049	-10000	0	-0.28	1	1
glial cell differentiation	-0.017	0.032	-10000	0	-10000	0	0
WWOX	0.014	0	-10000	0	-10000	0	0
cell proliferation	0.005	0.081	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class III

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
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	0.037	0.22	5	-0.14	5	10
CDKN1A	-0.005	0.088	-10000	0	-0.62	5	5
KAT2B	0.001	0.074	-10000	0	-0.42	8	8
BAX	0.014	0	-10000	0	-10000	0	0
FOXO3	-0.005	0.009	-10000	0	-10000	0	0
FOXO1	0.012	0.027	-10000	0	-0.42	1	1
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	0.003	0.023	-10000	0	-0.25	2	2
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.002	0.068	-10000	0	-0.25	16	16
PPARGC1A	-0.12	0.19	-10000	0	-0.38	88	88
FHL2	-0.008	0.093	-10000	0	-0.42	13	13
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.017	0.033	0.14	5	-0.31	2	7
HIST2H4A	0.014	0.038	0.14	5	-0.22	5	10
SIRT1/FOXO3a	0.003	0.028	-10000	0	-0.25	2	2
SIRT1	0.01	0.046	0.19	5	-0.44	2	7
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.025	0.029	-10000	0	-0.25	2	2
SIRT1/Histone H1b	0.014	0.045	0.15	4	-0.21	8	12
apoptosis	-0.025	0.029	0.25	2	-10000	0	2
SIRT1/PGC1A	-0.061	0.11	-10000	0	-0.22	89	89
p53/SIRT1	0	0.071	0.37	5	-0.3	7	12
SIRT1/FOXO4	0.021	0.029	0.15	5	-0.24	2	7
FOXO1/FHL2/SIRT1	0.011	0.058	0.13	4	-0.21	16	20
HIST1H1E	0.011	0.042	-10000	0	-0.24	7	7
SIRT1/p300	0.017	0.033	-10000	0	-0.31	2	2
muscle cell differentiation	-0.006	0.071	0.35	8	-0.14	4	12
TP53	0.005	0.064	0.19	5	-0.42	5	10
KU70/SIRT1/BAX	0.025	0.029	-10000	0	-0.25	2	2
CREBBP	0.014	0	-10000	0	-10000	0	0
MEF2D	0.014	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.01	0.036	-10000	0	-0.24	4	4
ACSS2	0.015	0.04	0.14	5	-0.3	3	8
SIRT1/PCAF/MYOD	0.006	0.071	0.14	4	-0.35	8	12

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	-0.005	0.11	-10000	0	-0.26	34	34
BAG4	0.005	0.059	-10000	0	-0.42	5	5
BAD	0.009	0.038	-10000	0	-0.12	9	9
NFKBIA	0.014	0	-10000	0	-10000	0	0
BIRC3	-0.058	0.15	-10000	0	-0.36	51	51
BAX	0.009	0.038	-10000	0	-0.12	9	9
EnzymeConsortium:3.1.4.12	0.001	0.027	-10000	0	-0.077	15	15
IKBKB	0	0.1	-10000	0	-0.3	15	15
MAP2K2	0.017	0.038	-10000	0	-0.21	1	1
MAP2K1	0.017	0.038	-10000	0	-0.21	1	1
SMPD1	0.005	0.031	-10000	0	-0.11	9	9
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.001	0.1	-10000	0	-0.31	15	15
MAP2K4	0.01	0.048	-10000	0	-0.2	7	7
protein ubiquitination	0.001	0.1	-10000	0	-0.3	16	16
EnzymeConsortium:2.7.1.37	0.019	0.041	-10000	0	-0.2	1	1
response to UV	0	0	-10000	0	-0.001	9	9
RAF1	0.013	0.039	-10000	0	-0.13	10	10
CRADD	0.013	0.016	-10000	0	-0.25	1	1
mol:ceramide	0.004	0.039	-10000	0	-0.13	10	10
I-kappa-B-alpha/RELA/p50/ubiquitin	0.019	0	-10000	0	-10000	0	0
MADD	0.014	0	-10000	0	-10000	0	0
MAP3K1	0.005	0.051	-10000	0	-0.16	15	15
TRADD	0.014	0	-10000	0	-10000	0	0
RELA/p50	0.014	0	-10000	0	-10000	0	0
MAPK3	0.02	0.037	-10000	0	-0.2	1	1
MAPK1	0.02	0.037	-10000	0	-0.2	1	1
p50/RELA/I-kappa-B-alpha	0.02	0	-10000	0	-10000	0	0
FADD	-0.005	0.1	-10000	0	-0.26	33	33
KSR1	0.009	0.041	-10000	0	-0.14	10	10
MAPK8	0.012	0.058	-10000	0	-0.26	7	7
TRAF2	0.014	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	0	0.1	-10000	0	-0.31	15	15
TNF R/SODD	0.015	0.042	-10000	0	-0.29	5	5
TNF	-0.025	0.11	-10000	0	-0.34	29	29
CYCS	0.012	0.039	0.12	5	-0.12	9	14
IKBKG	0	0.1	-10000	0	-0.3	15	15
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.01	0.11	-10000	0	-0.28	33	33
RELA	0.014	0	-10000	0	-10000	0	0
RIPK1	0.014	0	-10000	0	-10000	0	0
AIFM1	0.012	0.039	0.12	5	-0.12	9	14
TNF/TNF R/SODD	0	0.075	-10000	0	-0.24	20	20
TNFRSF1A	0.014	0	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.014	0.053	-10000	0	-0.72	1	1
NSMAF	-0.004	0.1	-10000	0	-0.31	15	15
response to hydrogen peroxide	0	0	-10000	0	-0.001	9	9
BCL2	0.001	0.074	-10000	0	-0.42	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	-0.29	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	-0.39	13	13
NFKBIA	-0.024	0.12	-9999	-0.26	40	40
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	-0.42	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	0.008	0.048	-9999	-0.38	4	4
NF kappa B1 p50 dimer	0.018	0	-9999	-10000	0	0
PIK3R1	0.01	0.037	-9999	-0.42	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	0.1	-9999	-0.24	40	40
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.002	0.1	-9999	-0.37	13	13
SRC	0.012	0.027	-9999	-0.42	1	1
PI3K	0.014	0.048	-9999	-0.31	5	5
NF kappa B1 p50/RelA	-0.015	0.1	-9999	-0.24	40	40
IKBKB	0.014	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.014	0	-9999	-10000	0	0
SYK	-0.009	0.094	-9999	-0.39	15	15
I kappa B alpha/PIK3R1	-0.017	0.11	-9999	-0.24	42	42
cell death	0.002	0.097	-9999	-0.36	13	13
NF kappa B1 p105/c-Rel	0.022	0.022	-9999	-0.24	2	2
LCK	-0.067	0.16	-9999	-0.37	56	56
BCL3	0.01	0.037	-9999	-0.42	2	2

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.025	0.16	-10000	0	-0.56	5	5
CRP	0.02	0.16	-10000	0	-0.75	2	2
cell cycle arrest	0.016	0.18	-10000	0	-0.57	9	9
TIMP1	0.03	0.16	-10000	0	-0.83	3	3
IL6ST	-0.01	0.1	-10000	0	-0.42	16	16
Rac1/GDP	-0.003	0.13	-10000	0	-0.35	23	23
AP1	0.048	0.058	-10000	0	-0.34	1	1
GAB2	0.013	0.023	-10000	0	-0.25	2	2
TNFSF11	-0.031	0.3	-10000	0	-0.98	21	21
HSP90B1	0.033	0.035	-10000	0	-10000	0	0
GAB1	0.011	0.038	-10000	0	-0.42	2	2
MAPK14	-0.004	0.13	-10000	0	-0.51	11	11
AKT1	0.044	0.05	-10000	0	-0.62	1	1
FOXO1	0.047	0.049	-10000	0	-0.59	1	1
MAP2K6	-0.003	0.12	0.22	1	-0.36	15	16
mol:GTP	0	0.002	-10000	0	-10000	0	0
MAP2K4	0.008	0.14	-10000	0	-0.4	18	18
MITF	-0.013	0.12	0.22	1	-0.32	17	18
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	-0.031	0.24	-10000	0	-1.3	9	9
CEBPB	0.02	0.003	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.026	0.055	0.23	3	-0.28	1	4
STAT3	0.015	0.18	-10000	0	-0.6	9	9
STAT1	0.001	0.077	-10000	0	-0.86	2	2
CEBPD	0.015	0.19	-10000	0	-0.88	5	5
PIK3CA	0.009	0.048	-10000	0	-0.38	4	4
PI3K	0.016	0.049	-10000	0	-0.31	5	5
JUN	0.013	0.016	-10000	0	-0.25	1	1
PIAS3/MITF	-0.007	0.11	0.21	1	-0.3	17	18
MAPK11	-0.008	0.14	-10000	0	-0.51	13	13
STAT3 (dimer)/FOXO1	0.046	0.17	-10000	0	-0.56	7	7
GRB2/SOS1/GAB family	0.013	0.1	0.19	3	-0.34	11	14
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.01	0.12	-10000	0	-0.33	22	22
GRB2	0.015	0.002	-10000	0	-10000	0	0
JAK2	0.004	0.061	-10000	0	-0.39	6	6
LBP	0.017	0.18	-10000	0	-0.76	6	6
PIK3R1	0.011	0.037	-10000	0	-0.42	2	2
JAK1	0.015	0.008	-10000	0	-10000	0	0
MYC	0.024	0.16	-10000	0	-0.63	3	3
FGG	0.018	0.16	-10000	0	-0.75	2	2
macrophage differentiation	0.016	0.18	-10000	0	-0.57	9	9
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0	0.11	-10000	0	-0.3	19	19
JUNB	0.023	0.15	-10000	0	-0.54	5	5
FOS	0.006	0.045	-10000	0	-0.25	8	8
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	0.005	0.11	0.24	1	-0.33	12	13
STAT1/PIAS1	0.017	0.099	0.24	1	-0.27	13	14
GRB2/SOS1/GAB family/SHP2/PI3K	0.037	0.053	-10000	0	-0.38	3	3
STAT3 (dimer)	0.015	0.18	-10000	0	-0.6	9	9
PRKCD	0.016	0.16	-10000	0	-0.47	16	16
IL6R	0.002	0.075	-10000	0	-0.42	8	8
SOCS3	-0.02	0.2	-10000	0	-1.1	8	8
gp130 (dimer)/JAK1/JAK1/LMO4	0.014	0.074	-10000	0	-0.23	20	20
Rac1/GTP	-0.001	0.14	-10000	0	-0.36	23	23
HCK	-0.011	0.1	-10000	0	-0.42	15	15
MAPKKK cascade	0.039	0.051	-10000	0	-0.39	1	1
bone resorption	-0.025	0.28	-10000	0	-0.9	21	21
IRF1	0.011	0.21	-10000	0	-0.82	9	9
mol:GDP	-0.01	0.13	-10000	0	-0.36	24	24
SOS1	0.015	0.004	-10000	0	-10000	0	0
VAV1	-0.01	0.13	-10000	0	-0.36	24	24
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.009	0.12	-10000	0	-0.41	16	16
PTPN11	0.016	0.017	-10000	0	-10000	0	0
IL6/IL6RA	-0.007	0.091	-10000	0	-0.23	34	34
gp130 (dimer)/TYK2/TYK2/LMO4	0.012	0.071	-10000	0	-0.23	20	20
gp130 (dimer)/JAK2/JAK2/LMO4	0.007	0.09	-10000	0	-0.29	20	20
IL6	-0.016	0.1	-10000	0	-0.3	27	27
PIAS3	0.014	0	-10000	0	-10000	0	0
PTPRE	-0.005	0.073	-10000	0	-0.39	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	0.087	0.22	1	-0.21	29	30
LMO4	0.01	0.054	-10000	0	-0.42	4	4
STAT3 (dimer)/PIAS3	0.02	0.17	-10000	0	-0.56	9	9
MCL1	0.048	0.046	-10000	0	-0.55	1	1

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.002	0.065	-9999	-0.21	20	20
RGS9BP	-0.002	0.076	-9999	-0.36	11	11
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0.002	0.005	-9999	-10000	0	0
mol:Na +	0.003	0.025	-9999	-0.13	9	9
mol:ADP	0.006	0.012	-9999	-0.16	1	1
GNAT2	0.013	0.004	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.012	0.088	-9999	-0.25	24	24
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0.011	0.013	-9999	-0.13	2	2
GRK7	0.007	0.017	-9999	-0.25	1	1
CNGB3	-0.003	0.044	-9999	-0.25	8	8
Cone Metarhodopsin II/X-Arrestin	0	0.015	-9999	-0.16	2	2
mol:Ca2+	-0.003	0.039	-9999	-0.23	1	1
Cone PDE6	-0.006	0.076	-9999	-0.21	25	25
Cone Metarhodopsin II	0.006	0.01	-9999	-10000	0	0
Na + (4 Units)	-0.001	0.04	-9999	-0.23	1	1
GNAT2/GDP	-0.002	0.075	-9999	-0.21	24	24
GNB5	0.006	0.055	-9999	-0.39	5	5
mol:GMP (4 units)	0.008	0.012	-9999	-10000	0	0
Cone Transducin	0.003	0.07	-9999	-0.22	20	20
SLC24A2	-0.01	0.064	-9999	-0.25	18	18
GNB3/GNGT2	-0.009	0.09	-9999	-0.26	28	28
GNB3	-0.007	0.084	-9999	-0.34	15	15
GNAT2/GTP	0.009	0.003	-9999	-10000	0	0
CNGA3	0.005	0.017	-9999	-0.25	1	1
ARR3	0	0.022	-9999	-0.25	2	2
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	0.003	0.025	-9999	-0.13	9	9
mol:Pi	-0.012	0.088	-9999	-0.25	24	24
Cone CNG Channel	0.01	0.024	-9999	-0.2	1	1
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.01	0.064	-9999	-0.25	18	18
RGS9	-0.03	0.12	-9999	-0.32	35	35
PDE6C	0.002	0.005	-9999	-10000	0	0
GNGT2	-0.009	0.095	-9999	-0.41	14	14
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.003	0.023	-9999	-0.25	2	2

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.012	0.027	-10000	0	-0.42	1	1
HDAC2	0.014	0.001	-10000	0	-10000	0	0
GNB1/GNG2	-0.016	0.098	-10000	0	-0.24	44	44
forebrain development	-0.023	0.13	-10000	0	-0.51	12	12
GNAO1	-0.067	0.17	-10000	0	-0.41	51	51
SMO/beta Arrestin2	-0.018	0.1	-10000	0	-0.29	34	34
SMO	-0.041	0.14	-10000	0	-0.42	34	34
ARRB2	0.014	0.002	-10000	0	-10000	0	0
GLI3/SPOP	0.043	0.077	-10000	0	-0.25	10	10
mol:GTP	0	0.001	-10000	0	-10000	0	0
GSK3B	0.014	0	-10000	0	-10000	0	0
GNAI2	0.014	0.001	-10000	0	-10000	0	0
SIN3/HDAC complex	0.034	0.009	-10000	0	-10000	0	0
GNAI1	0.009	0.046	-10000	0	-0.42	3	3
XPO1	0.015	0.003	-10000	0	-10000	0	0
GLI1/Su(fu)	-0.026	0.14	-10000	0	-0.43	15	15
SAP30	0.013	0.016	-10000	0	-0.25	1	1
mol:GDP	-0.041	0.14	-10000	0	-0.42	34	34
MIM/GLI2A	0.001	0.073	-10000	0	-0.38	9	9
IFT88	0.012	0.027	-10000	0	-0.42	1	1
GNAI3	0.014	0.001	-10000	0	-10000	0	0
GLI2	0.027	0.038	-10000	0	-10000	0	0
GLI3	0.037	0.081	0.17	8	-0.26	10	18
CSNK1D	0.014	0	-10000	0	-10000	0	0
CSNK1E	0.014	0	-10000	0	-10000	0	0
SAP18	0.014	0	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.012	0.026	-10000	0	-0.42	1	1
GNG2	-0.003	0.082	-10000	0	-0.42	10	10
Gi family/GTP	-0.062	0.14	-10000	0	-0.25	75	75
SIN3B	0.014	0.001	-10000	0	-10000	0	0
SIN3A	0.014	0	-10000	0	-10000	0	0
GLI3/Su(fu)	0.045	0.056	-10000	0	-0.56	1	1
GLI2/Su(fu)	0.025	0.058	-10000	0	-0.24	2	2
FOXA2	-0.028	0.12	-10000	0	-0.73	7	7
neural tube patterning	-0.023	0.13	-10000	0	-0.51	12	12
SPOP	0.014	0	-10000	0	-10000	0	0
Su(fu)/PIAS1	0.009	0.055	-10000	0	-10000	0	0
GNB1	0.014	0	-10000	0	-10000	0	0
CSNK1G2	0.01	0.037	-10000	0	-0.42	2	2
CSNK1G3	0.007	0.053	-10000	0	-0.42	4	4
MTSS1	0.001	0.073	-10000	0	-0.38	9	9
embryonic limb morphogenesis	-0.023	0.13	-10000	0	-0.51	12	12
SUFU	0.002	0.06	-10000	0	-10000	0	0
LGALS3	-0.009	0.097	-10000	0	-0.42	14	14
catabolic process	0.053	0.075	-10000	0	-0.45	2	2
GLI3A/CBP	0.008	0.058	-10000	0	-0.31	7	7
KIF3A	0.01	0.037	-10000	0	-0.42	2	2
GLI1	-0.024	0.14	-10000	0	-0.53	12	12
RAB23	0.014	0	-10000	0	-10000	0	0
CSNK1A1	0.014	0	-10000	0	-10000	0	0
IFT172	-0.001	0.078	-10000	0	-0.42	9	9
RBBP7	0.014	0.001	-10000	0	-10000	0	0
Su(fu)/Galectin3	-0.003	0.074	-10000	0	-0.21	14	14
GNAZ	-0.029	0.12	-10000	0	-0.39	28	28
RBBP4	0.014	0	-10000	0	-10000	0	0
CSNK1G1	0.014	0	-10000	0	-10000	0	0
PIAS1	0.014	0	-10000	0	-10000	0	0
PRKACA	0.014	0	-10000	0	-10000	0	0
GLI2/SPOP	0.033	0.036	-10000	0	-10000	0	0
STK36	0.015	0.003	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.054	0.13	-10000	0	-0.4	19	19
PTCH1	-0.026	0.18	-10000	0	-0.92	8	8
MIM/GLI1	-0.022	0.14	-10000	0	-0.47	15	15
CREBBP	0.008	0.058	-10000	0	-0.31	7	7
Su(fu)/SIN3/HDAC complex	0.034	0.025	-10000	0	-0.24	1	1

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0.018	0.058	-10000	0	-0.52	2	2
HDAC1	0.009	0.027	-10000	0	-0.42	1	1
AES	0.011	0.027	-10000	0	-0.42	1	1
FBXW11	0.014	0	-10000	0	-10000	0	0
DTX1	-0.022	0.1	-10000	0	-0.3	30	30
LRP6/FZD1	0.011	0.047	-10000	0	-0.2	11	11
TLE1	0.007	0.053	-10000	0	-0.42	4	4
AP1	-0.012	0.079	-10000	0	-0.22	31	31
NCSTN	0.014	0	-10000	0	-10000	0	0
ADAM10	0.012	0.027	-10000	0	-0.42	1	1
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.035	0.044	-10000	0	-10000	0	0
NICD/RBPSUH	0.027	0.047	-10000	0	-0.51	2	2
WIF1	-0.019	0.081	-10000	0	-0.26	26	26
NOTCH1	0.02	0.049	-10000	0	-0.55	2	2
PSENEN	0.014	0	-10000	0	-10000	0	0
KREMEN2	-0.023	0.11	-10000	0	-0.34	27	27
DKK1	-0.089	0.16	-10000	0	-0.32	82	82
beta catenin/beta TrCP1	0.041	0.049	0.21	1	-10000	0	1
APH1B	0.01	0.037	-10000	0	-0.42	2	2
APH1A	0.014	0	-10000	0	-10000	0	0
AXIN1	0	0.027	0.21	1	-0.21	2	3
CtBP/CBP/TCF1/TLE1/AES	0.015	0.04	-10000	0	-0.21	7	7
PSEN1	0.014	0	-10000	0	-10000	0	0
FOS	0.006	0.045	-10000	0	-0.25	8	8
JUN	0.013	0.016	-10000	0	-0.25	1	1
MAP3K7	0.011	0.027	-10000	0	-0.42	1	1
CTNNB1	0.035	0.052	0.22	1	-10000	0	1
MAPK3	0.014	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.013	0.095	-10000	0	-0.26	29	29
HNF1A	0.011	0.027	-10000	0	-0.42	1	1
CTBP1	0.013	0.001	-10000	0	-10000	0	0
MYC	0.019	0.017	-10000	0	-10000	0	0
NKD1	-0.048	0.15	-10000	0	-0.38	41	41
FZD1	0.004	0.056	-10000	0	-0.29	9	9
NOTCH1 precursor/Deltex homolog 1	0.01	0.067	-10000	0	-0.51	2	2
apoptosis	-0.012	0.079	-10000	0	-0.22	31	31
Delta 1/NOTCHprecursor	0.02	0.058	-10000	0	-0.51	2	2
DLL1	-0.001	0.071	-10000	0	-0.32	12	12
PPARD	0.02	0.013	-10000	0	-10000	0	0
Gamma Secretase	0.04	0.02	-10000	0	-0.19	2	2
APC	-0.003	0.044	0.21	1	-0.3	4	5
DVL1	0.019	0.041	-10000	0	-0.34	3	3
CSNK2A1	0.014	0.001	-10000	0	-10000	0	0
MAP3K7IP1	-0.001	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.056	0.11	-10000	0	-0.25	50	50
LRP6	0.01	0.037	-10000	0	-0.42	2	2
CSNK1A1	0.014	0.001	-10000	0	-10000	0	0
NLK	0.011	0.019	-10000	0	-0.28	1	1
CCND1	0	0.16	-10000	0	-1.3	4	4
WNT1	0.003	0.047	-10000	0	-0.25	9	9
Axin1/APC/beta catenin	0.04	0.047	0.25	1	-0.29	1	2
DKK2	-0.017	0.1	-10000	0	-0.35	22	22
NOTCH1 precursor/DVL1	0.033	0.063	-10000	0	-0.6	2	2
GSK3B	0.013	0	-10000	0	-10000	0	0
FRAT1	0.011	0.027	-10000	0	-0.42	1	1
NOTCH/Deltex homolog 1	0.009	0.067	-10000	0	-0.52	2	2
PPP2R5D	0.042	0.076	0.24	31	-10000	0	31
MAPK1	0.014	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.005	0.061	-10000	0	-0.22	9	9
RBPJ	0.014	0	-10000	0	-10000	0	0
CREBBP	0.016	0.003	-10000	0	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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
HDAC1	0.012	0.027	-10000	0	-0.42	1	1
HDAC3	0.014	0	-10000	0	-10000	0	0
VDR	0.004	0.064	-10000	0	-0.42	6	6
Cbp/p300/PCAF	0.02	0.045	-10000	0	-0.24	8	8
EP300	0.014	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.014	0.071	-10000	0	-0.34	5	5
KAT2B	0.001	0.074	-10000	0	-0.42	8	8
MAPK14	0.014	0	-10000	0	-10000	0	0
AKT1	0.01	0.078	0.19	9	-0.22	19	28
RAR alpha/9cRA/Cyclin H	0.024	0.078	-10000	0	-0.31	11	11
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.008	0.083	-10000	0	-0.33	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	0.068	-10000	0	-0.55	3	3
NCOR2	0.014	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.003	0.045	-10000	0	-0.3	6	6
RXRs/RARs/NRIP1/9cRA	-0.013	0.16	-10000	0	-0.58	14	14
NCOA2	0.003	0.066	-10000	0	-0.4	7	7
NCOA3	0.014	0	-10000	0	-10000	0	0
NCOA1	0.014	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.004	0.064	-10000	0	-0.42	6	6
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	0.009	0.047	-10000	0	-0.43	3	3
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.008	0.11	-10000	0	-0.42	14	14
RARA	0.008	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	0.003	0.1	-10000	0	-0.39	11	11
PRKCA	-0.004	0.087	-10000	0	-0.38	13	13
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.025	0.17	-10000	0	-0.62	14	14
RXRG	-0.06	0.13	-10000	0	-0.28	68	68
RXRA	0.012	0.065	-10000	0	-0.26	11	11
RXRB	0.007	0.061	-10000	0	-0.28	10	10
VDR/Vit D3/DNA	0.003	0.045	-10000	0	-0.3	6	6
RBP1	-0.031	0.12	-10000	0	-0.3	38	38
CRBP1/9-cic-RA	-0.021	0.079	-10000	0	-0.21	38	38
RARB	-0.02	0.12	-10000	0	-0.4	23	23
PRKCG	0.003	0.045	-10000	0	-0.24	8	8
MNAT1	0.014	0	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.004	0.14	-10000	0	-0.52	14	14
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.001	0.12	-10000	0	-0.41	14	14
proteasomal ubiquitin-dependent protein catabolic process	0.011	0.09	-10000	0	-0.48	5	5
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.024	0.17	-10000	0	-0.62	14	14
positive regulation of DNA binding	-0.014	0.065	-10000	0	-0.29	11	11
NRIP1	-0.032	0.22	-10000	0	-1.1	8	8
RXRs/RARs	-0.027	0.15	-10000	0	-0.48	19	19
RXRs/RXRs/DNA/9cRA	-0.01	0.11	-10000	0	-0.43	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

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.012	0.023	-9999	-0.25	2	2
Syndecan-3/Src/Cortactin	-0.006	0.071	-9999	-10000	0	0
Syndecan-3/Neurocan	0.012	0.025	-9999	-10000	0	0
POMC	-0.054	0.13	-9999	-0.3	57	57
EGFR	-0.021	0.1	-9999	-0.29	30	30
Syndecan-3/EGFR	0.007	0.047	-9999	-10000	0	0
AGRP	0.002	0.039	-9999	-0.25	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	-0.42	2	2
APH1A	0.014	0	-9999	-10000	0	0
NCAN	-0.001	0.052	-9999	-0.25	11	11
long-term memory	0.029	0.011	-9999	-10000	0	0
Syndecan-3/IL8	0.005	0.053	-9999	-10000	0	0
PSEN1	0.014	0	-9999	-10000	0	0
Src/Cortactin	0.018	0.024	-9999	-0.2	3	3
FYN	0.014	0	-9999	-10000	0	0
limb bud formation	0	0.004	-9999	-10000	0	0
MC4R	-0.002	0.052	-9999	-0.25	11	11
SRC	0.012	0.027	-9999	-0.42	1	1
PTN	-0.077	0.15	-9999	-0.31	74	74
FGFR/FGF/Syndecan-3	0	0.004	-9999	-10000	0	0
neuron projection morphogenesis	-0.01	0.069	-9999	-0.26	1	1
Syndecan-3/AgRP	0.01	0.02	-9999	-10000	0	0
Syndecan-3/AgRP/MC4R	0.015	0.03	-9999	-10000	0	0
Fyn/Cortactin	0.019	0.015	-9999	-0.16	2	2
SDC3	0	0.004	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	0.005	0.053	-9999	-10000	0	0
IL8	-0.024	0.11	-9999	-0.33	29	29
Syndecan-3/Fyn/Cortactin	0.03	0.011	-9999	-10000	0	0
Syndecan-3/CASK	0	0.003	-9999	-10000	0	0
alpha-MSH/MC4R	-0.036	0.1	-9999	-0.2	65	65
Gamma Secretase	0.039	0.02	-9999	-0.19	2	2

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.012	0.032	-10000	0	-0.42	1	1
AES	0.012	0.028	-10000	0	-0.37	1	1
FBXW11	0.014	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.011	0.047	-10000	0	-0.2	11	11
SMAD4	0.014	0	-10000	0	-10000	0	0
DKK2	-0.017	0.1	-10000	0	-0.35	22	22
TLE1	0.007	0.054	-10000	0	-0.41	4	4
MACF1	0.014	0	-10000	0	-10000	0	0
CTNNB1	0.024	0.052	-10000	0	-0.23	2	2
WIF1	-0.019	0.081	-10000	0	-0.26	26	26
beta catenin/RanBP3	0.013	0.087	0.34	15	-10000	0	15
KREMEN2	-0.023	0.11	-10000	0	-0.34	27	27
DKK1	-0.089	0.16	-10000	0	-0.32	82	82
beta catenin/beta TrCP1	0.031	0.05	-10000	0	-0.21	2	2
FZD1	0.004	0.056	-10000	0	-0.28	9	9
AXIN2	-0.044	0.27	-10000	0	-1.3	11	11
AXIN1	0.014	0	-10000	0	-10000	0	0
RAN	0.014	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.026	0.026	-10000	0	-0.28	1	1
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.032	0.07	-10000	0	-0.31	3	3
Axin1/APC/GSK3	0.038	0.039	0.17	1	-10000	0	1
Axin1/APC/GSK3/beta catenin/Macf1	0.033	0.049	-10000	0	-0.44	1	1
HNF1A	0.012	0.031	-10000	0	-0.42	1	1
CTBP1	0.014	0.016	-10000	0	-10000	0	0
MYC	0.006	0.052	-10000	0	-10000	0	0
RANBP3	0.014	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.013	0.095	-10000	0	-0.26	29	29
NKD1	-0.048	0.14	-10000	0	-0.38	41	41
TCF4	-0.004	0.076	-10000	0	-0.3	15	15
TCF3	0.014	0.016	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0.023	0.043	-10000	0	-0.21	4	4
Ran/GTP	0.01	0.001	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.014	0.11	0.4	15	-0.34	1	16
LEF1	-0.014	0.11	-10000	0	-0.42	17	17
DVL1	0.025	0.033	-10000	0	-0.24	3	3
CSNK2A1	0.014	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.029	0.088	-10000	0	-0.4	4	4
DKK1/LRP6/Kremen 2	-0.056	0.11	-10000	0	-0.25	50	50
LRP6	0.011	0.037	-10000	0	-0.42	2	2
CSNK1A1	0.014	0.018	-10000	0	-10000	0	0
NLK	0.014	0.003	-10000	0	-10000	0	0
CCND1	-0.012	0.17	-10000	0	-1.1	5	5
WNT1	0.003	0.047	-10000	0	-0.25	9	9
GSK3A	0.012	0.027	-10000	0	-0.42	1	1
GSK3B	0.014	0.001	-10000	0	-10000	0	0
FRAT1	0.012	0.026	-10000	0	-0.42	1	1
PPP2R5D	0.044	0.074	0.24	31	-10000	0	31
APC	0.018	0.046	-10000	0	-0.23	5	5
WNT1/LRP6/FZD1	0.026	0.04	0.2	2	-0.19	3	5
CREBBP	0.014	0.016	-10000	0	-10000	0	0

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	-0.068	0.14	-9999	-0.3	68	68
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.012	0.027	-9999	-0.42	1	1
TCEB1	0.014	0	-9999	-10000	0	0
HIF1A/p53	0.02	0.04	-9999	-0.22	6	6
HIF1A	0.016	0.029	-9999	-0.42	1	1
COPS5	0.014	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.038	0.024	-9999	-0.19	3	3
FIH (dimer)	0.012	0.026	-9999	-0.42	1	1
CDKN2A	-0.13	0.19	-9999	-0.37	100	100
ARNT/IPAS	-0.036	0.1	-9999	-0.2	68	68
HIF1AN	0.012	0.027	-9999	-0.42	1	1
GNB2L1	0.014	0	-9999	-10000	0	0
HIF1A/ARNT	0.024	0.028	-9999	-0.39	1	1
CUL2	0.01	0.037	-9999	-0.42	2	2
OS9	0.013	0.016	-9999	-0.25	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	0.031	-9999	-0.28	2	2
PHD1-3/OS9	0.029	0.038	-9999	-0.21	6	6
HIF1A/RACK1/Elongin B/Elongin C	0.035	0.029	-9999	-0.36	1	1
VHL	0.014	0	-9999	-10000	0	0
HSP90AA1	0.012	0.027	-9999	-0.42	1	1
HIF1A/JAB1	0.024	0.028	-9999	-0.39	1	1
EGLN3	0.003	0.066	-9999	-0.4	7	7
EGLN2	0.014	0	-9999	-10000	0	0
EGLN1	0.014	0	-9999	-10000	0	0
TP53	0.005	0.059	-9999	-0.42	5	5
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.031	0.022	-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	-0.042	0.094	-9999	-0.41	2	2

×

Regulation of Androgen receptor activity

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
HDAC1	0.017	0.019	-9999	-0.29	1	1
SMARCC1	0.008	0.01	-9999	-10000	0	0
REL	0.011	0.037	-9999	-0.42	2	2
HDAC7	-0.002	0.091	-9999	-0.3	5	5
JUN	0.013	0.016	-9999	-0.25	1	1
EP300	0.014	0	-9999	-10000	0	0
KAT2B	0.001	0.074	-9999	-0.42	8	8
KAT5	0.014	0	-9999	-10000	0	0
MAPK14	0.004	0.057	-9999	-0.3	9	9
FOXO1	0.012	0.027	-9999	-0.42	1	1
T-DHT/AR	0	0.096	-9999	-0.27	6	6
MAP2K6	-0.004	0.079	-9999	-0.42	9	9
BRM/BAF57	0.018	0.027	-9999	-0.29	2	2
MAP2K4	0.011	0.008	-9999	-10000	0	0
SMARCA2	0.01	0.037	-9999	-0.42	2	2
PDE9A	-0.11	0.33	-9999	-1	31	31
NCOA2	0.003	0.066	-9999	-0.4	7	7
CEBPA	-0.012	0.099	-9999	-0.37	18	18
EHMT2	0.013	0.001	-9999	-10000	0	0
cell proliferation	0.003	0.11	-9999	-0.37	6	6
NR0B1	-0.1	0.17	-9999	-0.35	83	83
EGR1	0.001	0.06	-9999	-0.28	11	11
RXRs/9cRA	-0.028	0.099	-9999	-0.21	59	59
AR/RACK1/Src	0.006	0.067	-9999	-0.26	5	5
AR/GR	0.001	0.072	-9999	-0.24	16	16
GNB2L1	0.013	0.001	-9999	-10000	0	0
PKN1	0.012	0.027	-9999	-0.42	1	1
RCHY1	0.014	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0.002	-9999	-10000	0	0
MAPK8	0.01	0.034	-9999	-0.29	3	3
T-DHT/AR/TIF2/CARM1	0.007	0.077	-9999	-0.28	9	9
SRC	0.008	0.053	-9999	-0.2	13	13
NR3C1	0.005	0.059	-9999	-0.42	5	5
KLK3	-0.052	0.096	-9999	-0.43	1	1
APPBP2	0.011	0.007	-9999	-10000	0	0
TRIM24	0.013	0.002	-9999	-10000	0	0
T-DHT/AR/TIP60	0.005	0.063	-9999	-0.22	12	12
TMPRSS2	-0.048	0.21	-9999	-0.98	11	11
RXRG	-0.085	0.18	-9999	-0.41	61	61
mol:9cRA	0	0.001	-9999	-10000	0	0
RXRA	0.014	0	-9999	-10000	0	0
RXRB	0.014	0	-9999	-10000	0	0
CARM1	0.013	0.002	-9999	-10000	0	0
NR2C2	0.01	0.038	-9999	-0.42	2	2
KLK2	-0.006	0.12	-9999	-0.44	10	10
AR	-0.001	0.068	-9999	-0.24	13	13
SENP1	0.014	0	-9999	-10000	0	0
HSP90AA1	0.012	0.027	-9999	-0.42	1	1
MDM2	0.011	0.027	-9999	-0.24	3	3
SRY	0	0.022	-9999	-0.25	2	2
GATA2	0	0.07	-9999	-0.33	11	11
MYST2	0.014	0	-9999	-10000	0	0
HOXB13	-0.13	0.2	-9999	-0.39	94	94
T-DHT/AR/RACK1/Src	0.008	0.065	-9999	-0.26	5	5
positive regulation of transcription	0	0.07	-9999	-0.33	11	11
DNAJA1	0.011	0.007	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.023	0.014	-9999	-0.18	1	1
NCOA1	0.018	0.003	-9999	-10000	0	0
SPDEF	0.003	0.045	-9999	-0.25	8	8
T-DHT/AR/TIF2	0.011	0.089	-9999	-0.41	7	7
T-DHT/AR/Hsp90	0.004	0.065	-9999	-0.22	13	13
GSK3B	0.013	0.002	-9999	-10000	0	0
NR2C1	0.014	0.001	-9999	-10000	0	0
mol:T-DHT	0.004	0.055	-9999	-0.22	12	12
SIRT1	0.01	0.037	-9999	-0.42	2	2
ZMIZ2	0.014	0.003	-9999	-10000	0	0
POU2F1	0.006	0.038	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.051	0.1	-9999	-0.24	35	35
CREBBP	0.014	0	-9999	-10000	0	0
SMARCE1	0.013	0.001	-9999	-10000	0	0

×

PLK2 and PLK4 events

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
PLK2	0.006	0.055	-9999	-0.39	5	5
PLK4	0.004	0.064	-9999	-0.42	6	6
regulation of centriole replication	0.007	0.063	-9999	-0.3	10	10

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.014	0	-10000	0	-10000	0	0
NFATC1	0.034	0.059	-10000	0	-0.24	8	8
NFATC2	0.015	0.047	-10000	0	-0.21	2	2
NFATC3	0.014	0.047	-10000	0	-0.32	5	5
YWHAE	0.014	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.032	0.13	-10000	0	-0.35	29	29
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	-0.038	0.15	-10000	0	-0.39	33	33
BCL2/BAX	0.011	0.053	-10000	0	-0.29	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	0.014	0	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.023	0.13	-10000	0	-0.37	24	24
Calcineurin A alpha-beta B1/BCL2	0.001	0.074	-10000	0	-0.42	8	8
FKBP8	0.012	0.027	-10000	0	-0.42	1	1
activation-induced cell death of T cells	0.023	0.12	0.36	24	-10000	0	24
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	-0.055	0.13	-10000	0	-0.28	61	61
MAP3K8	0	0.07	-10000	0	-0.33	11	11
NFAT4/CK1 alpha	0.022	0.041	-10000	0	-0.18	11	11
MEF2D/NFAT1/Cbp/p300	0.041	0.053	-10000	0	-0.25	3	3
CABIN1	-0.032	0.13	-10000	0	-0.38	26	26
CALM1	0.014	0.001	-10000	0	-10000	0	0
RAN	0.014	0	-10000	0	-10000	0	0
MAP3K1	0.004	0.064	-10000	0	-0.42	6	6
CAMK4	-0.05	0.14	-10000	0	-0.36	45	45
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	-0.001	0.072	-10000	0	-0.22	24	24
YWHAB	0.014	0	-10000	0	-10000	0	0
MAPK8	0.009	0.046	-10000	0	-0.42	3	3
MAPK9	0.014	0	-10000	0	-10000	0	0
YWHAG	0.014	0	-10000	0	-10000	0	0
FKBP1A	0.014	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.044	0.062	-10000	0	-0.24	9	9
PRKCH	0.012	0.027	-10000	0	-0.42	1	1
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	0.01	0.001	-10000	0	-10000	0	0
apoptosis	-0.002	0.018	0.19	1	-10000	0	1
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.019	0.039	-10000	0	-10000	0	0
PRKCB	-0.044	0.14	-10000	0	-0.35	42	42
PRKCE	0.013	0.016	-10000	0	-0.25	1	1
JNK2/NFAT4	0.021	0.043	-10000	0	-0.29	5	5
BAD/BCL-XL	0.02	0	-10000	0	-10000	0	0
PRKCD	0.012	0.027	-10000	0	-0.42	1	1
NUP214	0.014	0	-10000	0	-10000	0	0
PRKCZ	0.006	0.059	-10000	0	-0.42	5	5
PRKCA	-0.006	0.086	-10000	0	-0.38	13	13
PRKCG	0.001	0.044	-10000	0	-0.25	8	8
PRKCQ	-0.062	0.16	-10000	0	-0.39	50	50
FKBP38/BCL2	0.01	0.056	-10000	0	-0.29	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	0.06	-10000	0	-0.23	8	8
CaM/Ca2+/FKBP38	0.018	0.016	-10000	0	-0.24	1	1
FKBP12/FK506	0.01	0	-10000	0	-10000	0	0
CSNK1A1	0.017	0.003	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.018	0.087	-10000	0	-0.2	45	45
NFATc/ERK1	0.04	0.057	-10000	0	-0.23	8	8
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.038	0.15	-10000	0	-0.39	33	33
NR4A1	0.035	0.064	-10000	0	-0.44	3	3
GSK3B	0.014	0.001	-10000	0	-10000	0	0
positive T cell selection	0.014	0.047	-10000	0	-0.32	5	5
NFAT1/CK1 alpha	0.016	0.036	-10000	0	-0.17	1	1
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	-0.018	0.1	-10000	0	-0.33	24	24
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	0.04	0.057	-10000	0	-0.23	8	8
CREBBP	0.014	0.002	-10000	0	-10000	0	0
BCL2	0.001	0.074	-10000	0	-0.42	8	8

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.019	0.11	-10000	0	-0.37	23	23
HRAS	0.014	0	-10000	0	-10000	0	0
EGFR	-0.021	0.1	-10000	0	-0.29	30	30
AKT	0.026	0.029	-10000	0	-0.26	1	1
FOXO3	0.014	0	-10000	0	-10000	0	0
AKT1	0.014	0	-10000	0	-10000	0	0
FOXO1	0.012	0.027	-10000	0	-0.42	1	1
AKT3	0.012	0.027	-10000	0	-0.42	1	1
FOXO4	0.014	0	-10000	0	-10000	0	0
MET	-0.041	0.14	-10000	0	-0.37	38	38
PIK3CA	0.008	0.048	-10000	0	-0.38	4	4
PIK3CB	0.014	0	-10000	0	-10000	0	0
NRAS	0.014	0	-10000	0	-10000	0	0
PIK3CG	-0.034	0.13	-10000	0	-0.37	33	33
PIK3R3	0.013	0.016	-10000	0	-0.25	1	1
PIK3R2	0.014	0	-10000	0	-10000	0	0
NF1	0.009	0.046	-10000	0	-0.42	3	3
RAS	-0.015	0.075	0.18	2	-0.26	10	12
ERBB2	-0.001	0.078	-10000	0	-0.42	9	9
proliferation/survival/translation	-0.016	0.044	0.21	3	-10000	0	3
PI3K	-0.016	0.087	0.16	3	-0.24	20	23
PIK3R1	0.01	0.037	-10000	0	-0.42	2	2
KRAS	0.013	0.016	-10000	0	-0.25	1	1
FOXO	0.034	0.025	0.14	3	-10000	0	3
AKT2	0.014	0	-10000	0	-10000	0	0
PTEN	0.007	0.053	-10000	0	-0.42	4	4

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.082	0.3	-9999	-1.1	21	21
RAD9A	0.014	0	-9999	-10000	0	0
AP1	0.014	0.036	-9999	-0.24	2	2
IFNAR2	0.013	0.007	-9999	-10000	0	0
AKT1	0.004	0.04	-9999	-0.2	3	3
ER alpha/Oestrogen	-0.003	0.06	-9999	-0.28	12	12
NFX1/SIN3/HDAC complex	0.035	0.018	-9999	-10000	0	0
EGF	-0.089	0.17	-9999	-0.37	71	71
SMG5	0.014	0	-9999	-10000	0	0
SMG6	0.014	0	-9999	-10000	0	0
SP3/HDAC2	0.017	0.029	-9999	-0.29	2	2
TERT/c-Abl	-0.07	0.28	-9999	-0.99	21	21
SAP18	0.013	0.002	-9999	-10000	0	0
MRN complex	0.019	0.059	-9999	-0.35	6	6
WT1	-0.055	0.14	-9999	-0.34	49	49
WRN	0.009	0.046	-9999	-0.42	3	3
SP1	0.012	0.011	-9999	-10000	0	0
SP3	0.01	0.038	-9999	-0.42	2	2
TERF2IP	0.014	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.084	0.24	-9999	-0.87	21	21
Mad/Max	0.02	0.008	-9999	-10000	0	0
TERT	-0.087	0.32	-9999	-1.1	21	21
CCND1	-0.074	0.29	-9999	-0.96	24	24
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	0.013	0.007	-9999	-10000	0	0
PTGES3	0.014	0	-9999	-10000	0	0
SIN3A	0.013	0.002	-9999	-10000	0	0
Telomerase/911	0.026	0.034	-9999	-10000	0	0
CDKN1B	-0.035	0.11	-9999	-0.23	57	57
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	0.016	-9999	-0.25	1	1
TRF2/PARP2	0.021	0.006	-9999	-10000	0	0
UBE3A	0.013	0.004	-9999	-10000	0	0
JUN	0.012	0.016	-9999	-0.25	1	1
E6	-0.001	0.004	-9999	-10000	0	0
HPV-16 E6/E6AP	0.01	0.007	-9999	-10000	0	0
FOS	0.005	0.045	-9999	-0.25	8	8
IFN-gamma/IRF1	-0.05	0.13	-9999	-0.28	58	58
PARP2	0.014	0	-9999	-10000	0	0
BLM	0.01	0.037	-9999	-0.42	2	2
Telomerase	0.021	0.071	-9999	-0.35	6	6
IRF1	0.005	0.067	-9999	-0.37	8	8
ESR1	-0.005	0.085	-9999	-0.39	12	12
KU/TER	0.02	0	-9999	-10000	0	0
ATM/TRF2	0.018	0.03	-9999	-0.27	3	3
ubiquitin-dependent protein catabolic process	0.04	0.018	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.04	0.018	-9999	-10000	0	0
HDAC1	0.012	0.027	-9999	-0.42	1	1
HDAC2	0.012	0.01	-9999	-10000	0	0
ATM	-0.004	0.037	-9999	-0.35	3	3
SMAD3	0.012	0.046	-9999	-0.29	6	6
ABL1	0.014	0	-9999	-10000	0	0
MXD1	0.013	0.004	-9999	-10000	0	0
MRE11A	0.012	0.027	-9999	-0.42	1	1
HUS1	0.014	0	-9999	-10000	0	0
RPS6KB1	0.014	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.055	0.28	-9999	-0.96	21	21
NR2F2	0.015	0.008	-9999	-10000	0	0
MAPK3	0.008	0.022	-9999	-0.16	4	4
MAPK1	0.008	0.022	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.007	0.053	-9999	-0.42	4	4
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	-0.004	0.037	-9999	-0.35	3	3
NBN	0.009	0.046	-9999	-0.42	3	3
EGFR	-0.022	0.1	-9999	-0.29	30	30
mol:Oestrogen	0	0.003	-9999	-10000	0	0
EGF/EGFR	-0.075	0.14	-9999	-0.26	90	90
MYC	0.012	0.017	-9999	-0.25	1	1
IL2	-0.001	0.033	-9999	-0.24	4	4
KU	0.02	0	-9999	-10000	0	0
RAD50	0.005	0.059	-9999	-0.42	5	5
HSP90AA1	0.012	0.027	-9999	-0.42	1	1
TGFB1	0.007	0.053	-9999	-0.42	4	4
TRF2/BLM	0.018	0.025	-9999	-0.27	2	2
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.063	0.28	-9999	-0.99	21	21
SP1/HDAC2	0.019	0.017	-9999	-10000	0	0
PINX1	0.013	0.016	-9999	-0.25	1	1
Telomerase/EST1A	-0.084	0.24	-9999	-0.87	21	21
Smad3/Myc	0.018	0.04	-9999	-0.24	6	6
911 complex	0.028	0	-9999	-10000	0	0
IFNG	-0.082	0.17	-9999	-0.37	67	67
Telomerase/PinX1	-0.084	0.24	-9999	-0.87	21	21
Telomerase/AKT1/mTOR/p70S6K	0.01	0.063	-9999	-0.28	1	1
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	21	21
response to DNA damage stimulus	0.002	0.014	-9999	-0.12	3	3
MRN complex/TRF2/Rap1	0.032	0.05	-9999	-0.3	5	5
TRF2/WRN	0.017	0.03	-9999	-0.26	3	3
Telomerase/hnRNP C1/C2	-0.084	0.24	-9999	-0.87	21	21
E2F1	0.01	0.038	-9999	-0.42	2	2
ZNFX1	0.013	0.002	-9999	-10000	0	0
PIF1	0.005	0.059	-9999	-0.42	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

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.02	0.058	-9999	-0.19	27	27
TC10/GTP	-0.01	0.04	-9999	-0.27	1	1
Insulin Receptor/Insulin/IRS1/Shp2	0.015	0.056	-9999	-0.22	14	14
HRAS	0.014	0	-9999	-10000	0	0
APS homodimer	0.004	0.061	-9999	-0.39	6	6
GRB14	-0.063	0.15	-9999	-0.34	57	57
FOXO3	0.008	0.062	-9999	-0.54	3	3
AKT1	-0.009	0.084	-9999	-0.3	7	7
INSR	0.013	0.027	-9999	-0.42	1	1
Insulin Receptor/Insulin	0.032	0.021	-9999	-0.23	1	1
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.007	0.053	-9999	-0.42	4	4
SORBS1	-0.003	0.081	-9999	-0.39	11	11
CRK	0.014	0	-9999	-10000	0	0
PTPN1	0.023	0.02	-9999	-0.23	1	1
CAV1	0.009	0.052	-9999	-0.2	15	15
CBL/APS/CAP/Crk-II/C3G	0.027	0.054	-9999	-0.2	14	14
Insulin Receptor/Insulin/IRS1/NCK2	0.015	0.056	-9999	-0.22	14	14
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.009	0.059	-9999	-0.21	17	17
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.021	0.051	-9999	-0.35	2	2
RPS6KB1	-0.004	0.078	-9999	-0.28	7	7
PARD6A	0.009	0.041	-9999	-0.36	3	3
CBL	0.014	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	-0.002	0.046	-9999	-0.73	1	1
PIK3R1	0.01	0.037	-9999	-0.42	2	2
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.031	0.062	-9999	-0.28	7	7
HRAS/GTP	-0.017	0.051	-9999	-0.32	2	2
Insulin Receptor	0.013	0.027	-9999	-0.42	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.023	0.052	-9999	-0.2	14	14
PRKCI	-0.009	0.065	-9999	-0.5	4	4
Insulin Receptor/Insulin/GRB14/PDK1	-0.039	0.075	-9999	-0.31	8	8
SHC1	0.014	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0.023	0.044	-9999	-0.62	1	1
PI3K	0.014	0.062	-9999	-0.21	17	17
NCK2	0.014	0	-9999	-10000	0	0
RHOQ	0.014	0	-9999	-10000	0	0
mol:H2O2	0	0.002	-9999	-10000	0	0
HRAS/GDP	0.01	0	-9999	-10000	0	0
AKT2	-0.009	0.084	-9999	-0.29	8	8
PRKCZ	-0.011	0.071	-9999	-0.5	5	5
SH2B2	0.004	0.061	-9999	-0.39	6	6
SHC/SHIP	0.006	0.07	-9999	-0.2	25	25
F2RL2	-0.07	0.15	-9999	-0.33	65	65
TRIP10	0.012	0.027	-9999	-0.42	1	1
Insulin Receptor/Insulin/Shc	0.019	0.014	-9999	-0.2	1	1
TC10/GTP/CIP4/Exocyst	0.018	0.016	-9999	-0.24	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	0.01	0.037	-9999	-0.42	2	2
NCK1	0.014	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	0.021	0.057	-9999	-0.22	14	14
TC10/GDP	0.01	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.024	0.033	-9999	-0.21	5	5
INPP5D	-0.002	0.073	-9999	-0.22	25	25
SOS1	0.014	0	-9999	-10000	0	0
SGK1	-0.01	0.084	-9999	-0.8	3	3
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.014	0	-9999	-10000	0	0
IRS1	-0.009	0.095	-9999	-0.41	14	14
p62DOK/RasGAP	0.023	0.045	-9999	-0.63	1	1
INS	0.002	0.003	-9999	-10000	0	0
mol:PI-3-4-P2	-0.002	0.072	-9999	-0.22	25	25
GRB2	0.014	0	-9999	-10000	0	0
EIF4EBP1	-0.004	0.079	-9999	-0.27	8	8
PTPRA	0.015	0.003	-9999	-10000	0	0
PIK3CA	0.008	0.048	-9999	-0.38	4	4
TC10/GTP/CIP4	0.018	0.016	-9999	-0.24	1	1
PDPK1	0.014	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.016	0.05	-9999	-0.2	14	14
Insulin Receptor/Insulin/IRS1	0.007	0.055	-9999	-0.22	14	14
Insulin Receptor/Insulin/IRS3	0.012	0.019	-9999	-0.29	1	1
Par3/Par6	-0.014	0.081	-9999	-0.19	34	34

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.011	0.031	-10000	0	-0.33	2	2
mol:Halofuginone	0.004	0.005	-10000	0	-10000	0	0
ITGA1	0.003	0.056	-10000	0	-0.29	9	9
CDKN1A	0.016	0.061	-10000	0	-0.4	5	5
PRL-3/alpha Tubulin	0.015	0.039	-10000	0	-0.26	5	5
mol:Ca2+	-0.065	0.12	0.34	3	-0.22	85	88
AGT	-0.091	0.16	-10000	0	-0.31	86	86
CCNA2	0.022	0.039	-10000	0	-10000	0	0
TUBA1B	0.014	0	-10000	0	-10000	0	0
EGR1	0.012	0.041	-10000	0	-0.28	2	2
CDK2/Cyclin E1	0.022	0.068	-10000	0	-0.34	6	6
MAPK3	0.013	0.039	-10000	0	-0.26	5	5
PRL-2 /Rab GGTase beta	0.02	0	-10000	0	-10000	0	0
MAPK1	0.013	0.039	-10000	0	-0.29	4	4
PTP4A1	0.02	0.035	-10000	0	-10000	0	0
PTP4A3	0.006	0.055	-10000	0	-0.39	5	5
PTP4A2	0.014	0	-10000	0	-10000	0	0
ITGB1	0.013	0.04	-10000	0	-0.29	4	4
SRC	0.012	0.027	-10000	0	-0.42	1	1
RAC1	0.018	0.053	-10000	0	-0.39	4	4
Rab GGTase beta/Rab GGTase alpha	0.02	0	-10000	0	-10000	0	0
PRL-1/ATF-5	0.027	0.033	-10000	0	-10000	0	0
RABGGTA	0.014	0	-10000	0	-10000	0	0
BCAR1	0.003	0.041	0.34	3	-0.3	1	4
RHOC	0.018	0.053	-10000	0	-0.39	4	4
RHOA	0.018	0.053	-10000	0	-0.39	4	4
cell motility	0.019	0.058	-10000	0	-0.38	4	4
PRL-1/alpha Tubulin	0.027	0.033	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	0.008	0.054	-10000	0	-0.21	14	14
ROCK1	0.019	0.058	-10000	0	-0.38	4	4
RABGGTB	0.014	0	-10000	0	-10000	0	0
CDK2	0.001	0.074	-10000	0	-0.42	8	8
mitosis	0.02	0.034	-10000	0	-10000	0	0
ATF5	0.014	0	-10000	0	-10000	0	0

×

FOXM1 transcription factor network

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
NFATC3	0.13	0.27	-9999	-1	5	5
PLK1	0.05	0.13	-9999	-1.4	2	2
BIRC5	0.04	0.18	-9999	-1.4	4	4
HSPA1B	0.13	0.28	-9999	-1	6	6
MAP2K1	0.039	0.027	-9999	-10000	0	0
BRCA2	0.12	0.31	-9999	-1	10	10
FOXM1	0.12	0.35	-9999	-1.4	6	6
XRCC1	0.13	0.27	-9999	-1	5	5
FOXM1B/p19	-0.071	0.21	-9999	-0.96	7	7
Cyclin D1/CDK4	0.078	0.31	-9999	-0.97	7	7
CDC2	0.13	0.28	-9999	-1	6	6
TGFA	0.058	0.33	-9999	-0.96	8	8
SKP2	0.13	0.27	-9999	-1	5	5
CCNE1	0.016	0.032	-9999	-0.33	2	2
CKS1B	0.13	0.27	-9999	-1.1	4	4
RB1	-0.059	0.16	-9999	-0.74	10	10
FOXM1C/SP1	0.12	0.28	-9999	-1.1	6	6
AURKB	0.036	0.2	-9999	-1.3	5	5
CENPF	0.13	0.28	-9999	-1.1	5	5
CDK4	0.018	0.031	-9999	-0.24	3	3
MYC	0.13	0.24	-9999	-0.83	6	6
CHEK2	0.039	0.027	-9999	-10000	0	0
ONECUT1	0.079	0.32	-9999	-0.87	12	12
CDKN2A	-0.14	0.19	-9999	-0.38	100	100
LAMA4	0.12	0.31	-9999	-1.1	10	10
FOXM1B/HNF6	0.074	0.35	-9999	-1.2	8	8
FOS	0.13	0.27	-9999	-1.1	4	4
SP1	0.015	0.001	-9999	-10000	0	0
CDC25B	0.13	0.27	-9999	-1	5	5
response to radiation	0.021	0.025	-9999	-10000	0	0
CENPB	0.13	0.27	-9999	-1	5	5
CENPA	0.12	0.29	-9999	-1.3	5	5
NEK2	0.13	0.28	-9999	-1.1	5	5
HIST1H2BA	0.12	0.27	-9999	-1	5	5
CCNA2	0.014	0.048	-9999	-0.43	3	3
EP300	0.014	0	-9999	-10000	0	0
CCNB1/CDK1	0.13	0.3	-9999	-1.1	6	6
CCNB2	0.12	0.29	-9999	-1.1	8	8
CCNB1	0.13	0.28	-9999	-1	6	6
ETV5	0.13	0.28	-9999	-0.99	7	7
ESR1	0.1	0.33	-9999	-1	14	14
CCND1	0.081	0.32	-9999	-1	7	7
GSK3A	0.033	0.038	-9999	-0.43	1	1
Cyclin A-E1/CDK1-2	0.038	0.07	-9999	-0.26	11	11
CDK2	0.006	0.075	-9999	-0.42	8	8
G2/M transition of mitotic cell cycle	0.026	0.028	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.026	0.21	-9999	-1	6	6
GAS1	0.12	0.31	-9999	-1	10	10
MMP2	0.082	0.37	-9999	-1	21	21
RB1/FOXM1C	0.08	0.32	-9999	-0.98	8	8
CREBBP	0.014	0	-9999	-10000	0	0

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.017	0.07	-9999	-0.29	11	11
STMN1	0.011	0.055	-9999	-0.33	6	6
Aurora B/RasGAP/Survivin	0.018	0.062	-9999	-0.3	9	9
Chromosomal passenger complex/Cul3 protein complex	-0.026	0.098	-9999	-0.19	55	55
BIRC5	0.008	0.055	-9999	-0.44	4	4
DES	-0.075	0.21	-9999	-0.61	32	32
Aurora C/Aurora B/INCENP	0.012	0.054	-9999	-0.22	10	10
Aurora B/TACC1	0.014	0.036	-9999	-0.24	5	5
Aurora B/PP2A	0.015	0.043	-9999	-0.29	5	5
mol:GTP	0	0	-9999	-10000	0	0
CBX5	0.011	0.021	-9999	-0.14	5	5
mitotic metaphase/anaphase transition	0	0.002	-9999	-10000	0	0
NDC80	0.011	0.055	-9999	-0.34	6	6
Cul3 protein complex	-0.045	0.11	-9999	-0.24	54	54
KIF2C	0.01	0.084	-9999	-0.46	6	6
PEBP1	0.014	0.002	-9999	-10000	0	0
KIF20A	0.01	0.038	-9999	-0.42	2	2
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	0.013	0.05	-9999	-0.29	7	7
SEPT1	-0.018	0.099	-9999	-0.31	26	26
SMC2	0.012	0.027	-9999	-0.42	1	1
SMC4	0.009	0.046	-9999	-0.42	3	3
NSUN2/NPM1/Nucleolin	0.012	0.1	-9999	-0.72	5	5
PSMA3	0.014	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0	0.001	-9999	-10000	0	0
H3F3B	0.01	0.041	-9999	-0.29	5	5
AURKB	0.007	0.061	-9999	-0.43	5	5
AURKC	-0.006	0.079	-9999	-0.3	17	17
CDCA8	0.009	0.048	-9999	-0.44	3	3
cytokinesis	0.014	0.11	-9999	-0.66	6	6
Aurora B/Septin1	0.014	0.12	-9999	-0.65	6	6
AURKA	0.012	0.026	-9999	-0.42	1	1
INCENP	0.014	0.003	-9999	-10000	0	0
KLHL13	-0.095	0.17	-9999	-0.35	79	79
BUB1	0.009	0.046	-9999	-0.42	3	3
hSgo1/Aurora B/Survivin	0.018	0.063	-9999	-0.35	7	7
EVI5	0.009	0.046	-9999	-0.42	3	3
RhoA/GTP	0.029	0.09	-9999	-0.58	5	5
SGOL1	0.01	0.037	-9999	-0.42	2	2
CENPA	0.011	0.1	-9999	-0.6	6	6
NCAPG	0.009	0.046	-9999	-0.42	3	3
Aurora B/HC8 Proteasome	0.015	0.043	-9999	-0.29	5	5
NCAPD2	0.014	0	-9999	-10000	0	0
Aurora B/PP1-gamma	0.014	0.047	-9999	-0.29	6	6
RHOA	0.014	0	-9999	-10000	0	0
NCAPH	0.007	0.053	-9999	-0.42	4	4
NPM1	0.007	0.071	-9999	-0.5	5	5
RASA1	0.01	0.037	-9999	-0.42	2	2
KLHL9	0.002	0.069	-9999	-0.42	7	7
mitotic prometaphase	0	0.002	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.015	0.043	-9999	-0.29	5	5
PPP1CC	0.012	0.027	-9999	-0.42	1	1
Centraspindlin	0.026	0.099	-9999	-0.63	5	5
RhoA/GDP	0.01	0	-9999	-10000	0	0
NSUN2	0.007	0.071	-9999	-0.5	5	5
MYLK	0.006	0.052	-9999	-0.3	7	7
KIF23	0.011	0.039	-9999	-0.43	2	2
VIM	0.014	0.042	-9999	-0.29	5	5
RACGAP1	0.014	0.002	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
NCL	0.007	0.071	-9999	-0.5	5	5
Chromosomal passenger complex	0.016	0.094	-9999	-0.49	7	7
Chromosomal passenger complex/EVI5	0.03	0.074	-9999	-0.28	11	11
TACC1	0.014	0	-9999	-10000	0	0
PPP2R5D	0.014	0	-9999	-10000	0	0
CUL3	0.012	0.027	-9999	-0.42	1	1
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.034	0.091	-10000	0	-0.4	5	5
CRKL	0.014	0.064	-10000	0	-0.32	4	4
mol:DAG	0.021	0.071	-10000	0	-0.4	4	4
HRAS	0.03	0.06	-10000	0	-0.26	6	6
MAPK8	0.017	0.045	-10000	0	-0.24	6	6
RAP1A	0.015	0.064	-10000	0	-0.32	4	4
GAB1	0.013	0.069	-10000	0	-0.3	7	7
MAPK14	0.02	0.036	-10000	0	-0.24	3	3
EPO	0.001	0.047	-10000	0	-0.25	9	9
PLCG1	0.022	0.072	-10000	0	-0.4	4	4
EPOR/TRPC2/IP3 Receptors	0.013	0.008	-10000	0	-10000	0	0
RAPGEF1	0.014	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.013	0.057	-10000	0	-0.27	8	8
GAB1/SHC/GRB2/SOS1	0.027	0.063	-10000	0	-0.28	6	6
EPO/EPOR (dimer)	0.012	0.034	-10000	0	-0.16	9	9
IRS2	0.014	0.065	-10000	0	-0.24	9	9
STAT1	0.025	0.087	-10000	0	-0.41	6	6
STAT5B	0.024	0.076	-10000	0	-0.4	4	4
cell proliferation	0.02	0.042	-10000	0	-0.22	6	6
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.025	0.076	-10000	0	-0.31	15	15
TEC	0.007	0.079	-10000	0	-0.23	17	17
SOCS3	0	0.076	-10000	0	-0.4	9	9
STAT1 (dimer)	0.025	0.086	-10000	0	-0.4	6	6
JAK2	0.004	0.061	-10000	0	-0.39	6	6
PIK3R1	0.01	0.037	-10000	0	-0.42	2	2
EPO/EPOR (dimer)/JAK2	0.025	0.073	-10000	0	-0.26	8	8
EPO/EPOR	0.012	0.034	-10000	0	-0.16	9	9
LYN	0.01	0.046	-10000	0	-0.42	3	3
TEC/VAV2	0.01	0.086	-10000	0	-0.36	6	6
elevation of cytosolic calcium ion concentration	0.013	0.008	-10000	0	-10000	0	0
SHC1	0.014	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	0.024	0.043	-10000	0	-0.28	3	3
mol:IP3	0.021	0.071	-10000	0	-0.4	4	4
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.015	0.095	-10000	0	-0.33	14	14
SH2B3	0.008	0.049	-10000	0	-0.45	3	3
NFKB1	0.02	0.036	-10000	0	-0.24	3	3
EPO/EPOR (dimer)/JAK2/SOCS3	-0.002	0.048	0.24	1	-0.23	8	9
PTPN6	0.01	0.067	-10000	0	-0.25	9	9
TEC/VAV2/GRB2	0.016	0.084	-10000	0	-0.35	6	6
EPOR	0.013	0.008	-10000	0	-10000	0	0
INPP5D	-0.011	0.097	-10000	0	-0.39	16	16
mol:GDP	0.027	0.064	-10000	0	-0.28	6	6
SOS1	0.014	0	-10000	0	-10000	0	0
PLCG2	-0.004	0.083	-10000	0	-0.38	12	12
CRKL/CBL/C3G	0.029	0.062	-10000	0	-0.3	4	4
VAV2	0.009	0.074	-10000	0	-0.23	14	14
CBL	0.015	0.064	-10000	0	-0.32	4	4
SHC/Grb2/SOS1	-0.015	0.047	-10000	0	-0.3	4	4
STAT5A	0.022	0.084	-10000	0	-0.4	6	6
GRB2	0.014	0	-10000	0	-10000	0	0
STAT5 (dimer)	0.034	0.093	-10000	0	-0.32	12	12
LYN/PLCgamma2	0.006	0.073	-10000	0	-0.3	13	13
PTPN11	0.014	0	-10000	0	-10000	0	0
BTK	0.003	0.092	-10000	0	-0.25	24	24
BCL2	0.019	0.16	-10000	0	-0.67	12	12

×

PDGFR-beta 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.005	0.073	-9999	-0.32	8	8
PDGFB-D/PDGFRB/SLAP	0.001	0.076	-9999	-0.29	17	17
PDGFB-D/PDGFRB/APS/CBL	0.02	0.044	-9999	-0.24	7	7
AKT1	0.031	0.049	-9999	-0.47	1	1
mol:PI-4-5-P2	0	0.001	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.005	0.076	-9999	-0.34	8	8
PIK3CA	0.008	0.048	-9999	-0.38	4	4
FGR	-0.02	0.11	-9999	-0.46	14	14
mol:Ca2+	0.006	0.066	-9999	-0.47	3	3
MYC	0.016	0.07	-9999	-0.36	3	3
SHC1	0.014	0	-9999	-10000	0	0
HRAS/GDP	0.027	0.035	-9999	-0.23	4	4
LRP1/PDGFRB/PDGFB	0.025	0.026	-9999	-0.24	2	2
GRB10	0.007	0.053	-9999	-0.42	4	4
PTPN11	0.014	0	-9999	-10000	0	0
GO:0007205	0.006	0.067	-9999	-0.48	3	3
PTEN	0.007	0.053	-9999	-0.42	4	4
GRB2	0.014	0	-9999	-10000	0	0
GRB7	-0.013	0.077	-9999	-0.26	24	24
PDGFB-D/PDGFRB/SHP2	0.018	0.027	-9999	-0.29	2	2
PDGFB-D/PDGFRB/GRB10	0.014	0.046	-9999	-0.29	6	6
cell cycle arrest	0.001	0.075	-9999	-0.29	17	17
HRAS	0.014	0	-9999	-10000	0	0
HIF1A	0.034	0.045	-9999	-0.41	1	1
GAB1	-0.003	0.084	-9999	-0.35	8	8
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.002	0.078	-9999	-0.36	6	6
PDGFB-D/PDGFRB	0.027	0.031	-9999	-0.25	3	3
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.018	0.029	-9999	-0.25	3	3
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.016	0.069	-9999	-0.31	10	10
positive regulation of MAPKKK cascade	0.018	0.027	-9999	-0.29	2	2
PIK3R1	0.01	0.037	-9999	-0.42	2	2
mol:IP3	0.006	0.067	-9999	-0.48	3	3
E5	0	0.001	-9999	-10000	0	0
CSK	0.013	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	0	0.059	-9999	-0.17	26	26
SHB	-0.019	0.11	-9999	-0.36	23	23
BLK	-0.07	0.18	-9999	-0.5	35	35
PTPN2	0.012	0.027	-9999	-0.43	1	1
PDGFB-D/PDGFRB/SNX15	0.018	0.027	-9999	-0.29	2	2
BCAR1	0.01	0.037	-9999	-0.42	2	2
VAV2	-0.002	0.093	-9999	-0.4	8	8
CBL	0.014	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.016	0.038	-9999	-0.29	4	4
LCK	-0.076	0.18	-9999	-0.49	42	42
PDGFRB	0.011	0.038	-9999	-0.43	2	2
ACP1	0.013	0.016	-9999	-0.25	1	1
HCK	-0.026	0.12	-9999	-0.48	18	18
ABL1	-0.008	0.088	-9999	-0.29	16	16
PDGFB-D/PDGFRB/CBL	-0.004	0.089	-9999	-0.4	7	7
PTPN1	0.013	0.016	-9999	-0.25	1	1
SNX15	0.014	0	-9999	-10000	0	0
STAT3	0.014	0	-9999	-10000	0	0
STAT1	0.01	0.037	-9999	-0.42	2	2
cell proliferation	0.016	0.066	-9999	-0.33	3	3
SLA	-0.01	0.098	-9999	-0.41	15	15
actin cytoskeleton reorganization	0.022	0.061	-9999	-0.36	1	1
SRC	-0.001	0.044	-9999	-0.33	4	4
PI3K	-0.009	0.045	-9999	-0.52	1	1
PDGFB-D/PDGFRB/GRB7/SHC	0.011	0.05	-9999	-0.24	3	3
SH2B2	0.004	0.061	-9999	-0.39	6	6
PLCgamma1/SPHK1	0.005	0.078	-9999	-0.34	8	8
LYN	-0.003	0.066	-9999	-0.4	6	6
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	0.01	0.037	-9999	-0.42	2	2
NCK1-2/p130 Cas	0.039	0.031	-9999	-0.18	3	3
SPHK1	-0.007	0.084	-9999	-0.32	17	17
EDG1	0	0.002	-9999	-10000	0	0
mol:DAG	0.006	0.067	-9999	-0.48	3	3
PLCG1	0.006	0.069	-9999	-0.49	3	3
NHERF/PDGFRB	0.023	0.035	-9999	-0.24	4	4
YES1	-0.006	0.077	-9999	-0.47	6	6
cell migration	0.023	0.035	-9999	-0.24	4	4
SHC/Grb2/SOS1	0.041	0.025	-9999	-0.18	2	2
SLC9A3R2	0.011	0.031	-9999	-0.33	2	2
SLC9A3R1	0.011	0.031	-9999	-0.33	2	2
NHERF1-2/PDGFRB/PTEN	0.027	0.043	-9999	-0.21	8	8
FYN	0.002	0.032	-9999	-0.27	3	3
DOK1	0.022	0.031	-9999	-0.22	4	4
HRAS/GTP	0.01	0	-9999	-10000	0	0
PDGFB	0.012	0.023	-9999	-0.25	2	2
RAC1	0.009	0.087	-9999	-0.38	7	7
PRKCD	0.022	0.031	-9999	-0.22	4	4
FER	0.02	0.044	-9999	-0.25	6	6
MAPKKK cascade	-0.002	0.02	-9999	-10000	0	0
RASA1	0.022	0.039	-9999	-0.27	4	4
NCK1	0.014	0	-9999	-10000	0	0
NCK2	0.014	0	-9999	-10000	0	0
p62DOK/Csk	0.029	0.029	-9999	-0.19	4	4
PDGFB-D/PDGFRB/SHB	-0.005	0.081	-9999	-0.25	25	25
chemotaxis	-0.007	0.086	-9999	-0.28	16	16
STAT1-3-5/STAT1-3-5	0.006	0.038	-9999	-0.37	1	1
Bovine Papilomavirus E5/PDGFRB	0.008	0.027	-9999	-0.3	2	2
PTPRJ	0.01	0.037	-9999	-0.42	2	2

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.011	0.021	-10000	0	-0.2	2	2
TRAF2/ASK1	0.015	0.026	-10000	0	-0.24	2	2
ATM	0.009	0.046	-10000	0	-0.42	3	3
MAP2K3	0.012	0.08	-10000	0	-0.39	8	8
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.011	0.074	-10000	0	-0.29	8	8
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	-0.03	0.12	-10000	0	-0.37	30	30
TXN	0.007	0	-10000	0	-10000	0	0
CALM1	0.014	0	-10000	0	-10000	0	0
GADD45A	0.011	0.028	-10000	0	-0.25	3	3
GADD45B	0.013	0.016	-10000	0	-0.25	1	1
MAP3K1	0.004	0.064	-10000	0	-0.42	6	6
MAP3K6	0.014	0	-10000	0	-10000	0	0
MAP3K7	0.012	0.027	-10000	0	-0.42	1	1
MAP3K4	0.014	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.017	0.031	-10000	0	-0.29	2	2
TAK1/TAB family	0.001	0.024	0.15	5	-0.2	1	6
RAC1/OSM/MEKK3	0.026	0	-10000	0	-10000	0	0
TRAF2	0.014	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.009	0.055	-10000	0	-0.3	8	8
TRAF6	0.007	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	-0.036	0.12	-10000	0	-0.3	42	42
CCM2	0.014	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.01	0.068	-10000	0	-0.16	42	42
MAPK11	0.005	0.059	-10000	0	-0.42	5	5
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.003	0.066	-10000	0	-0.21	14	14
OSM/MEKK3	0.02	0	-10000	0	-10000	0	0
TAOK1	0.003	0.064	-10000	0	-0.32	9	9
TAOK2	0.011	0.031	-10000	0	-0.28	3	3
TAOK3	0.011	0.031	-10000	0	-0.28	3	3
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	0.008	0.044	-10000	0	-0.33	4	4
MAP3K10	0.009	0.046	-10000	0	-0.42	3	3
MAP3K3	0.014	0	-10000	0	-10000	0	0
TRX/ASK1	0.013	0.025	-10000	0	-0.18	4	4
GADD45/MTK1/MTK1	0.008	0.065	-10000	0	-0.19	21	21

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.008	0.068	0.32	5	-10000	0	5
KIRREL	0.004	0.06	-10000	0	-0.43	5	5
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.008	0.068	-10000	0	-0.32	5	5
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	0.004	0.053	-10000	0	-0.23	7	7
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.014	0.038	-10000	0	-0.22	5	5
FYN	0.001	0.043	-10000	0	-0.22	5	5
mol:Ca2+	0.005	0.048	-10000	0	-0.23	5	5
mol:DAG	0.006	0.049	-10000	0	-0.23	5	5
NPHS2	0	0.009	-10000	0	-10000	0	0
mol:IP3	0.006	0.049	-10000	0	-0.23	5	5
regulation of endocytosis	0.011	0.042	-10000	0	-0.2	5	5
Nephrin/NEPH1/podocin/Cholesterol	-0.002	0.048	-10000	0	-0.23	5	5
establishment of cell polarity	-0.008	0.068	-10000	0	-0.32	5	5
Nephrin/NEPH1/podocin/NCK1-2	0.015	0.045	-10000	0	-0.2	5	5
Nephrin/NEPH1/beta Arrestin2	0.012	0.043	-10000	0	-0.2	5	5
NPHS1	-0.019	0.078	-10000	0	-0.25	28	28
Nephrin/NEPH1/podocin	0.002	0.044	-10000	0	-0.22	5	5
TJP1	0.005	0.059	-10000	0	-0.42	5	5
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	0.049	-10000	0	-0.23	5	5
CD2AP	0.01	0.037	-10000	0	-0.42	2	2
Nephrin/NEPH1/podocin/GRB2	0.006	0.049	-10000	0	-0.23	5	5
GRB2	0.014	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.003	0.053	-10000	0	-0.21	9	9
cytoskeleton organization	0.015	0.042	-10000	0	-0.23	5	5
Nephrin/NEPH1	-0.003	0.046	-10000	0	-0.22	5	5
Nephrin/NEPH1/ZO-1	0	0.066	-10000	0	-0.26	10	10

×

BARD1 signaling events

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
BARD1/CSTF1	0.013	0.046	-10000	0	-0.29	6	6
ATM	0.009	0.046	-10000	0	-0.42	3	3
UBE2D3	0.014	0	-10000	0	-10000	0	0
PRKDC	0.014	0	-10000	0	-10000	0	0
ATR	0.012	0.027	-10000	0	-0.42	1	1
UBE2L3	0.014	0	-10000	0	-10000	0	0
FANCD2	0.016	0.04	-10000	0	-0.27	5	5
protein ubiquitination	0.02	0.066	-10000	0	-0.22	18	18
XRCC5	0.014	0	-10000	0	-10000	0	0
XRCC6	0.014	0	-10000	0	-10000	0	0
M/R/N Complex	0.019	0.059	-10000	0	-0.35	6	6
MRE11A	0.012	0.027	-10000	0	-0.42	1	1
DNA-PK	0.028	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.038	0.025	-10000	0	-10000	0	0
FANCF	0.014	0	-10000	0	-10000	0	0
BRCA1	0.01	0.037	-10000	0	-0.42	2	2
CCNE1	0.011	0.031	-10000	0	-0.33	2	2
CDK2/Cyclin E1	0.009	0.057	-10000	0	-0.28	10	10
FANCG	0.014	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.011	0.061	-10000	0	-0.37	6	6
FANCE	0.014	0	-10000	0	-10000	0	0
FANCC	0.014	0	-10000	0	-10000	0	0
NBN	0.009	0.046	-10000	0	-0.42	3	3
FANCA	0.014	0	-10000	0	-10000	0	0
DNA repair	0.045	0.052	-10000	0	-0.38	2	2
BRCA1/BARD1/ubiquitin	0.011	0.061	-10000	0	-0.37	6	6
BARD1/DNA-PK	0.03	0.036	-10000	0	-0.21	6	6
FANCL	0.012	0.027	-10000	0	-0.42	1	1
mRNA polyadenylation	-0.013	0.046	0.29	6	-10000	0	6
BRCA1/BARD1/CTIP/M/R/N Complex	0.013	0.11	-10000	0	-0.44	11	11
BRCA1/BACH1/BARD1/TopBP1	0.02	0.053	-10000	0	-0.31	6	6
BRCA1/BARD1/P53	0.023	0.06	-10000	0	-0.24	12	12
BARD1/CSTF1/BRCA1	0.02	0.053	-10000	0	-0.31	6	6
BRCA1/BACH1	0.01	0.037	-10000	0	-0.42	2	2
BARD1	0.004	0.064	-10000	0	-0.42	6	6
PCNA	0.014	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	0.02	0.053	-10000	0	-0.31	6	6
BRCA1/BARD1/UbcH7	0.02	0.053	-10000	0	-0.31	6	6
BRCA1/BARD1/RAD51/PCNA	0.026	0.053	-10000	0	-0.26	8	8
BARD1/DNA-PK/P53	0.031	0.046	-10000	0	-0.19	11	11
BRCA1/BARD1/Ubiquitin	0.011	0.061	-10000	0	-0.37	6	6
BRCA1/BARD1/CTIP	0.018	0.066	-10000	0	-0.28	11	11
FA complex	0.033	0.017	-10000	0	-10000	0	0
BARD1/EWS	0.013	0.046	-10000	0	-0.29	6	6
RBBP8	0.011	0.054	-10000	0	-0.33	6	6
TP53	0.005	0.059	-10000	0	-0.42	5	5
TOPBP1	0.014	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.022	0.06	0.24	12	-10000	0	12
BRCA1/BARD1	0.023	0.067	-10000	0	-0.22	18	18
CSTF1	0.014	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.003	0.045	-10000	0	-0.3	6	6
CDK2	0.001	0.074	-10000	0	-0.42	8	8
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.01	0.037	-10000	0	-0.42	2	2
RAD50	0.005	0.059	-10000	0	-0.42	5	5
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.011	0.061	-10000	0	-0.37	6	6
EWSR1	0.014	0	-10000	0	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.007	0.14	-10000	0	-0.99	5	5
regulation of axonogenesis	-0.017	0.032	0.3	1	-10000	0	1
myoblast fusion	-0.008	0.056	0.35	5	-10000	0	5
mol:GTP	0.004	0.033	-10000	0	-0.21	5	5
regulation of calcium-dependent cell-cell adhesion	-0.01	0.078	0.25	19	-10000	0	19
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	0.015	0.037	-10000	0	-0.27	3	3
lamellipodium assembly	0.012	0.059	-10000	0	-0.37	5	5
MAPK3	0.014	0.049	-10000	0	-0.31	5	5
ARF6/GTP/NME1/Tiam1	0.011	0.078	-10000	0	-0.25	19	19
ARF1	0.014	0	-10000	0	-10000	0	0
ARF6/GDP	0.008	0.056	-10000	0	-0.35	5	5
ARF1/GDP	0.016	0.052	-10000	0	-0.32	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	-0.41	18	18
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.014	0.049	-10000	0	-0.31	5	5
actin filament bundle formation	-0.012	0.051	0.32	5	-10000	0	5
KALRN	-0.01	0.05	-10000	0	-0.23	10	10
RAB11FIP3/RAB11A	0.02	0	-10000	0	-10000	0	0
RhoA/GDP	0.012	0.051	-10000	0	-0.32	5	5
NME1	0.014	0.004	-10000	0	-10000	0	0
Rac1/GDP	0.012	0.051	-10000	0	-0.32	5	5
substrate adhesion-dependent cell spreading	0.004	0.033	-10000	0	-0.21	5	5
cortical actin cytoskeleton organization	0.012	0.059	-10000	0	-0.38	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	-0.15	5	5
mol:GDP	0.01	0.056	-10000	0	-0.35	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	0.01	0.042	-10000	0	-0.22	7	7
RAB11FIP3	0.014	0	-10000	0	-10000	0	0
tube morphogenesis	0.012	0.059	-10000	0	-0.37	5	5
ruffle organization	0.017	0.032	-10000	0	-0.3	1	1
regulation of epithelial cell migration	0.004	0.033	-10000	0	-0.21	5	5
PLD2	0.013	0.025	-10000	0	-0.15	5	5
PIP5K1A	0.017	0.032	-10000	0	-0.3	1	1
mol:Phosphatidic acid	0.015	0.037	-10000	0	-0.27	3	3
Rac1/GTP	0.012	0.059	-10000	0	-0.38	5	5

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.014	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	0.011	0.052	-9999	-0.21	10	10
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	0.01	0.018	-9999	-10000	0	0
AURKB	0.005	0.059	-9999	-0.42	5	5
AURKC	-0.006	0.079	-9999	-0.3	17	17

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	0.02	0.071	0.17	1	-0.29	8	9
CaM/Ca2+	0.01	0	-10000	0	-10000	0	0
AKT1	0.014	0	-10000	0	-10000	0	0
AKT2	0.014	0	-10000	0	-10000	0	0
STXBP4	0.009	0.046	-10000	0	-0.42	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.022	0.071	0.17	1	-0.33	6	7
YWHAZ	0.014	0	-10000	0	-10000	0	0
CALM1	0.014	0	-10000	0	-10000	0	0
YWHAQ	0.014	0	-10000	0	-10000	0	0
TBC1D4	0.014	0.034	-10000	0	-0.2	6	6
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.014	0	-10000	0	-10000	0	0
YWHAB	0.014	0	-10000	0	-10000	0	0
SNARE/Synip	0.025	0.028	-10000	0	-0.24	3	3
YWHAG	0.014	0	-10000	0	-10000	0	0
ASIP	-0.011	0.071	-10000	0	-0.25	22	22
PRKCI	0.009	0.046	-10000	0	-0.42	3	3
AS160/CaM/Ca2+	0.01	0	-10000	0	-10000	0	0
RHOQ	0.014	0	-10000	0	-10000	0	0
GYS1	0.025	0	-10000	0	-10000	0	0
PRKCZ	0.005	0.059	-10000	0	-0.42	5	5
TRIP10	0.012	0.027	-10000	0	-0.42	1	1
TC10/GTP/CIP4/Exocyst	0.018	0.016	-10000	0	-0.24	1	1
AS160/14-3-3	0.017	0.046	-10000	0	-10000	0	0
VAMP2	0.014	0	-10000	0	-10000	0	0
SLC2A4	0.021	0.077	0.18	1	-0.36	6	7
STX4	0.014	0	-10000	0	-10000	0	0
GSK3B	0.022	0	-10000	0	-10000	0	0
SFN	-0.055	0.13	-10000	0	-0.28	61	61
LNPEP	0.004	0.064	-10000	0	-0.42	6	6
YWHAE	0.014	0	-10000	0	-10000	0	0

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.014	0	-10000	0	-10000	0	0
mol:PIP3	-0.013	0.071	0.23	4	-0.26	16	20
FRAP1	0.009	0.021	-10000	0	-10000	0	0
AKT1	0.007	0.065	0.2	4	-0.22	16	20
INSR	0.012	0.027	-10000	0	-0.42	1	1
Insulin Receptor/Insulin	0.008	0.016	-10000	0	-0.25	1	1
mol:GTP	0.015	0.052	-10000	0	-0.31	2	2
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.004	0.016	-10000	0	-10000	0	0
TSC2	0.014	0	-10000	0	-10000	0	0
RHEB/GDP	-0.01	0.039	-10000	0	-0.28	2	2
TSC1	0.012	0.027	-10000	0	-0.42	1	1
Insulin Receptor/IRS1	-0.001	0.07	-10000	0	-0.3	14	14
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.005	0.018	-10000	0	-0.14	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.014	0	-10000	0	-10000	0	0
RPS6KB1	0.015	0.04	0.16	4	-0.22	2	6
MAP3K5	0.006	0.031	-10000	0	-0.33	2	2
PIK3R1	0.01	0.038	-10000	0	-0.42	2	2
apoptosis	0.005	0.031	-10000	0	-0.33	2	2
mol:LY294002	0	0	0.001	1	-0.001	13	14
EIF4B	0.019	0.037	0.16	4	-0.19	2	6
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.023	0.032	-10000	0	-0.18	2	2
eIF4E/eIF4G1/eIF4A1	-0.001	0.01	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.005	0.075	-10000	0	-0.28	16	16
mTOR/RHEB/GTP/Raptor/GBL	0.018	0.031	0.15	4	-0.15	3	7
FKBP1A	0.014	0	-10000	0	-10000	0	0
RHEB/GTP	0.018	0.046	-10000	0	-0.28	2	2
mol:Amino Acids	0	0	0.001	1	-0.001	13	14
FKBP12/Rapamycin	0.01	0.001	-10000	0	-10000	0	0
PDPK1	0.004	0.068	0.21	4	-0.24	16	20
EIF4E	0.012	0.027	-10000	0	-0.42	1	1
ASK1/PP5C	0.015	0.054	-10000	0	-0.58	2	2
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.013	0.026	-10000	0	-0.41	1	1
TSC1/TSC2	0.02	0.06	0.2	4	-0.33	2	6
tumor necrosis factor receptor activity	0	0	0.001	13	-0.001	1	14
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	-0.009	0.073	-10000	0	-0.33	13	13
INS	0	0.001	-10000	0	-10000	0	0
PTEN	0.007	0.053	-10000	0	-0.42	4	4
PDK2	0.002	0.07	0.21	4	-0.23	18	22
EIF4EBP1	0.013	0.003	-10000	0	-10000	0	0
PIK3CA	0.008	0.048	-10000	0	-0.38	4	4
PPP2R5D	0.014	0.02	-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	0.003	4	-0.002	2	6
EEF2	0.014	0.014	-10000	0	-0.22	1	1
eIF4E/4E-BP1	0.019	0.015	-10000	0	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.037	0.12	-9999	-0.27	52	52
AKT1	0.036	0.098	-9999	-0.47	6	6
PTK2B	-0.006	0.095	-9999	-0.33	8	8
VEGFR2 homodimer/Frs2	0.026	0.044	-9999	-0.57	1	1
CAV1	0.012	0.027	-9999	-0.42	1	1
CALM1	0.014	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.03	0.051	-9999	-0.52	1	1
endothelial cell proliferation	0.024	0.11	-9999	-0.41	8	8
mol:Ca2+	0.03	0.056	-9999	-0.47	1	1
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.038	0.048	-9999	-0.49	1	1
RP11-342D11.1	0.022	0.055	-9999	-0.48	1	1
CDH5	0.013	0.016	-9999	-0.25	1	1
VEGFA homodimer	0.031	0.028	-9999	-0.2	1	1
SHC1	0.014	0	-9999	-10000	0	0
SHC2	-0.046	0.14	-9999	-0.37	41	41
HRAS/GDP	-0.009	0.038	-9999	-0.4	1	1
SH2D2A	-0.009	0.094	-9999	-0.39	15	15
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.036	0.095	-9999	-0.46	6	6
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.019	0.078	-9999	-0.46	3	3
VEGFR1 homodimer	0.011	0.031	-9999	-0.33	2	2
SHC/GRB2/SOS1	0.041	0.054	-9999	-0.44	1	1
GRB10	0.026	0.077	-9999	-0.47	5	5
PTPN11	0.014	0	-9999	-10000	0	0
GRB2	0.014	0	-9999	-10000	0	0
PAK1	0.012	0.023	-9999	-0.25	2	2
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.042	0.047	-9999	-0.47	1	1
HRAS	0.014	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	-0.003	0.1	-9999	-0.33	11	11
HIF1A	0.014	0	-9999	-10000	0	0
FRS2	0.013	0.016	-9999	-0.25	1	1
oxygen and reactive oxygen species metabolic process	0.036	0.047	-9999	-0.49	1	1
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.006	0.049	-9999	-0.3	6	6
Nck/Pak	0.019	0.015	-9999	-0.16	2	2
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.031	0.05	-9999	-0.52	1	1
mol:GDP	-0.009	0.041	-9999	-0.43	1	1
mol:NADP	0.038	0.076	-9999	-0.4	5	5
eNOS/Hsp90	0.043	0.073	-9999	-0.38	5	5
PIK3R1	0.01	0.037	-9999	-0.42	2	2
mol:IP3	0.03	0.057	-9999	-0.48	1	1
HIF1A/ARNT	0.02	0	-9999	-10000	0	0
SHB	-0.019	0.11	-9999	-0.36	23	23
VEGFA	0.005	0.052	-9999	-0.26	9	9
VEGFC	0.006	0.047	-9999	-0.27	7	7
FAK1/Vinculin	0.013	0.095	-9999	-0.38	6	6
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.004	0.1	-9999	-0.38	6	6
PTPN6	-0.012	0.1	-9999	-0.39	17	17
EPAS1	0.019	0.026	-9999	-0.31	1	1
mol:L-citrulline	0.038	0.076	-9999	-0.4	5	5
ITGAV	0.004	0.061	-9999	-0.39	6	6
PIK3CA	0.008	0.048	-9999	-0.38	4	4
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.037	0.048	-9999	-0.49	1	1
VEGFR2 homodimer/VEGFA homodimer	0.031	0.062	-9999	-0.52	1	1
VEGFR2/3 heterodimer	0.023	0.059	-9999	-0.78	1	1
VEGFB	0.014	0	-9999	-10000	0	0
MAPK11	0.028	0.063	-9999	-0.36	3	3
VEGFR2 homodimer	0.023	0.05	-9999	-0.66	1	1
FLT1	0.011	0.031	-9999	-0.33	2	2
NEDD4	0.01	0.046	-9999	-0.42	3	3
MAPK3	0.016	0.064	-9999	-0.39	2	2
MAPK1	0.016	0.064	-9999	-0.39	2	2
VEGFA145/NRP2	0.01	0.056	-9999	-0.34	5	5
VEGFR1/2 heterodimer	0.025	0.046	-9999	-0.57	1	1
KDR	0.023	0.05	-9999	-0.66	1	1
VEGFA165/NRP1/VEGFR2 homodimer	0.032	0.064	-9999	-0.34	3	3
SRC	0.012	0.027	-9999	-0.42	1	1
platelet activating factor biosynthetic process	0.018	0.064	-9999	-0.4	2	2
PI3K	0.029	0.1	-9999	-0.45	8	8
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.031	0.05	-9999	-0.52	1	1
FES	0.024	0.071	-9999	-0.43	3	3
GAB1	0.038	0.064	-9999	-0.47	2	2
VEGFR2 homodimer/VEGFA homodimer/Src	0.03	0.052	-9999	-0.52	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	0.043	0.073	-9999	-0.38	5	5
VEGFR2 homodimer/VEGFA homodimer/Yes	0.027	0.057	-9999	-0.52	1	1
PI3K/GAB1	0.039	0.1	-9999	-0.42	9	9
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.041	0.048	-9999	-0.47	1	1
PRKACA	0.014	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.026	0.06	-9999	-0.72	1	1
HSP90AA1	0.012	0.027	-9999	-0.42	1	1
CDC42	0.03	0.057	-9999	-0.48	1	1
actin cytoskeleton reorganization	0.018	0.077	-9999	-0.45	3	3
PTK2	0.005	0.099	-9999	-0.4	6	6
EDG1	0.022	0.055	-9999	-0.48	1	1
mol:DAG	0.03	0.057	-9999	-0.48	1	1
CaM/Ca2+	0.034	0.053	-9999	-0.44	1	1
MAP2K3	0.03	0.06	-9999	-0.41	2	2
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.033	0.08	-9999	-0.47	5	5
PLCG1	0.03	0.057	-9999	-0.48	1	1
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.021	0.079	-9999	-0.36	5	5
IQGAP1	0.014	0	-9999	-10000	0	0
YES1	0.007	0.053	-9999	-0.42	4	4
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.031	0.05	-9999	-0.52	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.017	0.074	-9999	-0.43	2	2
cell migration	0.032	0.085	-9999	-0.43	2	2
mol:PI-3-4-5-P3	0.029	0.096	-9999	-0.42	8	8
FYN	0.014	0	-9999	-10000	0	0
VEGFB/NRP1	0.029	0.053	-9999	-0.45	1	1
mol:NO	0.038	0.076	-9999	-0.4	5	5
PXN	0.014	0	-9999	-10000	0	0
HRAS/GTP	-0.009	0.038	-9999	-0.4	1	1
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.032	0.079	-9999	-0.47	5	5
VHL	0.014	0	-9999	-10000	0	0
ITGB3	-0.058	0.16	-9999	-0.38	49	49
NOS3	0.038	0.084	-9999	-0.45	5	5
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.002	0.092	-9999	-0.42	3	3
RAC1	0.014	0	-9999	-10000	0	0
PRKCA	0.023	0.067	-9999	-0.44	1	1
PRKCB	0.005	0.086	-9999	-0.52	2	2
VCL	0.014	0	-9999	-10000	0	0
VEGFA165/NRP1	0.025	0.057	-9999	-0.48	1	1
VEGFR1/2 heterodimer/VEGFA homodimer	0.029	0.054	-9999	-0.52	1	1
VEGFA165/NRP2	0.01	0.056	-9999	-0.34	5	5
MAPKKK cascade	0.046	0.068	-9999	-0.39	5	5
NRP2	0.007	0.053	-9999	-0.42	4	4
VEGFC homodimer	0.006	0.047	-9999	-0.27	7	7
NCK1	0.014	0	-9999	-10000	0	0
ROCK1	0.005	0.059	-9999	-0.42	5	5
FAK1/Paxillin	0.013	0.095	-9999	-0.38	6	6
MAP3K13	0.027	0.064	-9999	-0.43	2	2
PDPK1	0.032	0.087	-9999	-0.37	8	8

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	0.054	0.045	-9999	-0.22	1	1
ERC1	0.014	0	-9999	-10000	0	0
RIP2/NOD2	0.005	0.064	-9999	-0.24	16	16
NFKBIA	0.034	0	-9999	-10000	0	0
BIRC2	0.004	0.061	-9999	-0.39	6	6
IKBKB	0.014	0	-9999	-10000	0	0
RIPK2	0.014	0	-9999	-10000	0	0
IKBKG	0.025	0.049	-9999	-0.29	1	1
IKK complex/A20	0.026	0.073	-9999	-0.3	5	5
NEMO/A20/RIP2	0.014	0	-9999	-10000	0	0
XPO1	0.014	0	-9999	-10000	0	0
NEMO/ATM	0.029	0.058	-9999	-0.41	2	2
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.014	0	-9999	-10000	0	0
Exportin 1/RanGTP	0.019	0	-9999	-10000	0	0
IKK complex/ELKS	-0.008	0.036	-9999	-0.28	2	2
BCL10/MALT1/TRAF6	0.025	0.025	-9999	-0.24	2	2
NOD2	-0.009	0.09	-9999	-0.36	16	16
NFKB1	0.016	0	-9999	-10000	0	0
RELA	0.016	0	-9999	-10000	0	0
MALT1	0.01	0.037	-9999	-0.42	2	2
cIAP1/UbcH5C	0.014	0.043	-9999	-0.27	6	6
ATM	0.009	0.046	-9999	-0.42	3	3
TNF/TNFR1A	-0.007	0.08	-9999	-0.22	29	29
TRAF6	0.014	0	-9999	-10000	0	0
PRKCA	-0.006	0.086	-9999	-0.38	13	13
CHUK	0.012	0.027	-9999	-0.42	1	1
UBE2D3	0.014	0	-9999	-10000	0	0
TNF	-0.025	0.11	-9999	-0.34	29	29
NF kappa B1 p50/RelA	0.038	0	-9999	-10000	0	0
BCL10	0.013	0.016	-9999	-0.25	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.034	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	0.037	0.051	-9999	-0.3	2	2
CYLD	0.014	0	-9999	-10000	0	0
IKK complex/PKC alpha	0.033	0.065	-9999	-0.28	4	4

×

Circadian rhythm 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
chromatin modification	0.037	0.023	-9999	-10000	0	0
CLOCK	0.009	0.055	-9999	-0.38	5	5
TIMELESS/CRY2	0.032	0.02	-9999	-10000	0	0
DEC1/BMAL1	0.008	0.036	-9999	-0.17	10	10
ATR	0.012	0.027	-9999	-0.42	1	1
NR1D1	0.028	0.022	-9999	-10000	0	0
ARNTL	0.015	0.026	-9999	-0.42	1	1
TIMELESS	0.028	0.022	-9999	-10000	0	0
NPAS2	-0.016	0.11	-9999	-0.42	20	20
CRY2	0.014	0	-9999	-10000	0	0
mol:CO	-0.011	0	-9999	-10000	0	0
CHEK1	0.014	0	-9999	-10000	0	0
mol:HEME	0.011	0	-9999	-10000	0	0
PER1	0.014	0	-9999	-10000	0	0
BMAL/CLOCK/NPAS2	0.016	0.082	-9999	-0.24	24	24
BMAL1/CLOCK	0.028	0.055	-9999	-0.36	1	1
S phase of mitotic cell cycle	0.037	0.023	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	0.037	0.023	-9999	-10000	0	0
mol:NADPH	0.011	0	-9999	-10000	0	0
PER1/TIMELESS	0.032	0.02	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	-0.004	0.046	-9999	-0.25	9	9

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.022	0.02	-9999	-10000	0	0
BIRC5	0.007	0.053	-9999	-0.42	4	4
NFKBIA	0.023	0.013	-9999	-10000	0	0
CPEB1	-0.053	0.16	-9999	-0.42	41	41
AKT1	0.023	0.013	-9999	-10000	0	0
NDEL1	0.014	0	-9999	-10000	0	0
Aurora A/BRCA1	0.02	0.021	-9999	-0.18	2	2
NDEL1/TACC3	0.029	0.011	-9999	-10000	0	0
GADD45A	0.011	0.028	-9999	-0.25	3	3
GSK3B	0.013	0.006	-9999	-10000	0	0
PAK1/Aurora A	0.023	0.018	-9999	-10000	0	0
MDM2	0.011	0.028	-9999	-0.25	3	3
JUB	0.011	0.031	-9999	-0.33	2	2
TPX2	0.016	0.027	-9999	-0.29	2	2
TP53	0.019	0.042	-9999	-0.28	5	5
DLG7	0.016	0.013	-9999	-0.15	1	1
AURKAIP1	0.012	0.027	-9999	-0.42	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	0.012	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.019	0.021	-9999	-0.18	2	2
AURKA	0.02	0.017	-9999	-0.19	1	1
AURKB	0.006	0.056	-9999	-0.33	6	6
CDC25B	0.023	0.015	-9999	-10000	0	0
G2/M transition checkpoint	0.02	0.02	-9999	-0.21	1	1
mRNA polyadenylation	-0.014	0.084	-9999	-0.21	40	40
Aurora A/CPEB	-0.014	0.084	-9999	-0.21	40	40
Aurora A/TACC1/TRAP/chTOG	0.036	0.026	-9999	-0.19	3	3
BRCA1	0.01	0.037	-9999	-0.42	2	2
centrosome duplication	0.023	0.018	-9999	-10000	0	0
regulation of centrosome cycle	0.028	0.011	-9999	-10000	0	0
spindle assembly	0.034	0.026	-9999	-0.19	3	3
TDRD7	0.009	0.046	-9999	-0.42	3	3
Aurora A/RasGAP/Survivin	0.029	0.042	-9999	-0.24	5	5
CENPA	0.01	0.055	-9999	-0.41	4	4
Aurora A/PP2A	0.024	0.013	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.025	0.021	-9999	-10000	0	0
negative regulation of DNA binding	0.019	0.042	-9999	-0.28	5	5
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0.02	0	-9999	-10000	0	0
RASA1	0.01	0.037	-9999	-0.42	2	2
Ajuba/Aurora A	0.02	0.02	-9999	-0.21	1	1
mitotic prometaphase	0.001	0.011	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.02	0.017	-9999	-0.19	1	1
TACC1	0.014	0	-9999	-10000	0	0
TACC3	0.014	0	-9999	-10000	0	0
Aurora A/Antizyme1	0.03	0.019	-9999	-0.21	1	1
Aurora A/RasGAP	0.022	0.026	-9999	-0.23	2	2
OAZ1	0.014	0	-9999	-10000	0	0
RAN	0.014	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.013	0.006	-9999	-10000	0	0
GIT1	0.014	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0.027	0.013	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	0.016	0.027	-9999	-0.29	2	2
PPP2R5D	0.014	0	-9999	-10000	0	0
Aurora A/TPX2	0.026	0.026	-9999	-0.35	1	1
PAK1	0.012	0.023	-9999	-0.25	2	2
CKAP5	0.014	0	-9999	-10000	0	0

×

FoxO family signaling

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
G6PC	0.02	0.042	-9999	-10000	0	0
PLK1	0.035	0.16	-9999	-0.93	3	3
CDKN1B	0.11	0.068	-9999	-0.39	2	2
FOXO3	0.036	0.14	-9999	-0.47	7	7
KAT2B	0.004	0.077	-9999	-0.43	8	8
FOXO1/SIRT1	0.03	0.049	-9999	-0.19	11	11
CAT	0.04	0.13	-9999	-0.53	2	2
CTNNB1	0.014	0	-9999	-10000	0	0
AKT1	0.019	0.015	-9999	-10000	0	0
FOXO1	0.021	0.046	-9999	-0.22	9	9
MAPK10	0.007	0.059	-9999	-0.19	13	13
mol:GTP	0.002	0.001	-9999	-10000	0	0
FOXO4	0.065	0.051	-9999	-0.32	2	2
response to oxidative stress	0.007	0.015	-9999	-10000	0	0
FOXO3A/SIRT1	0.084	0.1	-9999	-0.49	5	5
XPO1	0.014	0	-9999	-10000	0	0
EP300	0.015	0.001	-9999	-10000	0	0
BCL2L11	0.019	0.035	-9999	-10000	0	0
FOXO1/SKP2	0.025	0.043	-9999	-0.19	9	9
mol:GDP	0.007	0.015	-9999	-10000	0	0
RAN	0.015	0.001	-9999	-10000	0	0
GADD45A	0.088	0.069	-9999	-0.54	2	2
YWHAQ	0.014	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.043	0.045	-9999	-10000	0	0
MST1	0.011	0.054	-9999	-0.41	4	4
CSNK1D	0.014	0	-9999	-10000	0	0
CSNK1E	0.014	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.028	0.057	-9999	-10000	0	0
YWHAB	0.014	0	-9999	-10000	0	0
MAPK8	0.029	0.027	-9999	-0.22	3	3
MAPK9	0.031	0.007	-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	0.018	0.044	-9999	-0.42	2	2
SOD2	0.094	0.083	-9999	-0.47	2	2
RBL2	0.048	0.15	-9999	-1.2	2	2
RAL/GDP	0.027	0.011	-9999	-10000	0	0
CHUK	0.016	0.031	-9999	-0.42	1	1
Ran/GTP	0.014	0.001	-9999	-10000	0	0
CSNK1G2	0.01	0.037	-9999	-0.42	2	2
RAL/GTP	0.033	0.011	-9999	-10000	0	0
CSNK1G1	0.014	0	-9999	-10000	0	0
FASLG	-0.2	0.49	-9999	-1.3	45	45
SKP2	0.013	0.016	-9999	-0.25	1	1
USP7	0.015	0.001	-9999	-10000	0	0
IKBKB	0.017	0.015	-9999	-10000	0	0
CCNB1	0.041	0.13	-9999	-0.51	3	3
FOXO1-3a-4/beta catenin	0.084	0.1	-9999	-0.4	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.025	0.042	-9999	-0.19	9	9
CSNK1A1	0.014	0	-9999	-10000	0	0
SGK1	0.012	0.049	-9999	-0.43	3	3
CSNK1G3	0.007	0.053	-9999	-0.42	4	4
Ran/GTP/Exportin 1	0.024	0.002	-9999	-10000	0	0
ZFAND5	0.067	0.045	-9999	-10000	0	0
SFN	-0.055	0.13	-9999	-0.28	61	61
CDK2	0.001	0.074	-9999	-0.42	8	8
FOXO3A/14-3-3	0.032	0.06	-9999	-0.32	1	1
CREBBP	0.014	0.001	-9999	-10000	0	0
FBXO32	0.032	0.18	-9999	-1.3	3	3
BCL6	0.055	0.1	-9999	-10000	0	0
RALB	0.015	0	-9999	-10000	0	0
RALA	0.015	0	-9999	-10000	0	0
YWHAH	0.014	0	-9999	-10000	0	0

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.027	0.039	-9999	-0.58	1	1
VEGFR1 homodimer/NRP1	0.016	0.038	-9999	-0.58	1	1
mol:DAG	0.013	0.066	-9999	-0.52	1	1
VEGFR1 homodimer/NRP1/VEGFR 121	0.02	0.046	-9999	-0.33	3	3
CaM/Ca2+	0.02	0.062	-9999	-0.49	1	1
HIF1A	0.02	0.022	-9999	-0.31	1	1
GAB1	0.01	0.037	-9999	-0.42	2	2
AKT1	0.022	0.079	-9999	-0.57	2	2
PLCG1	0.013	0.066	-9999	-0.53	1	1
NOS3	0.024	0.083	-9999	-0.51	3	3
CBL	0.014	0	-9999	-10000	0	0
mol:NO	0.025	0.08	-9999	-0.49	3	3
FLT1	0.023	0.044	-9999	-0.66	1	1
PGF	-0.017	0.11	-9999	-0.37	21	21
VEGFR1 homodimer/NRP2/VEGFR121	0.025	0.058	-9999	-0.36	4	4
CALM1	0.014	0	-9999	-10000	0	0
PIK3CA	0.008	0.048	-9999	-0.38	4	4
eNOS/Hsp90	0.031	0.08	-9999	-0.47	3	3
endothelial cell proliferation	-0.011	0.1	-9999	-0.42	7	7
mol:Ca2+	0.013	0.065	-9999	-0.52	1	1
MAPK3	0.011	0.069	-9999	-0.46	1	1
MAPK1	0.011	0.069	-9999	-0.34	2	2
PIK3R1	0.01	0.037	-9999	-0.42	2	2
PLGF homodimer	-0.017	0.11	-9999	-0.37	21	21
PRKACA	0.014	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	0.012	0.027	-9999	-0.42	1	1
VEGFA homodimer	0.004	0.052	-9999	-0.27	9	9
VEGFR1 homodimer/VEGFA homodimer	0.021	0.05	-9999	-0.36	3	3
platelet activating factor biosynthetic process	0.015	0.067	-9999	-0.44	1	1
PI3K	0.02	0.078	-9999	-0.54	2	2
PRKCA	0.007	0.073	-9999	-0.36	2	2
PRKCB	-0.012	0.092	-9999	-0.39	5	5
VEGFR1 homodimer/PLGF homodimer	0.009	0.073	-9999	-0.25	16	16
VEGFA	0.004	0.052	-9999	-0.27	9	9
VEGFB	0.014	0	-9999	-10000	0	0
mol:IP3	0.013	0.066	-9999	-0.52	1	1
RASA1	0.027	0.041	-9999	-0.53	1	1
NRP2	0.007	0.053	-9999	-0.42	4	4
VEGFR1 homodimer	0.023	0.044	-9999	-0.66	1	1
VEGFB homodimer	0.014	0	-9999	-10000	0	0
NCK1	0.014	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.031	0.08	-9999	-0.47	3	3
PTPN11	0.014	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.019	0.076	-9999	-0.53	2	2
mol:L-citrulline	0.025	0.08	-9999	-0.49	3	3
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.034	0.048	-9999	-0.36	2	2
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.029	0.046	-9999	-0.39	2	2
CD2AP	0.01	0.037	-9999	-0.42	2	2
PI3K/GAB1	0.024	0.08	-9999	-0.61	2	2
PDPK1	0.018	0.071	-9999	-0.5	2	2
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.029	0.046	-9999	-0.39	2	2
mol:NADP	0.025	0.08	-9999	-0.49	3	3
HSP90AA1	0.012	0.027	-9999	-0.42	1	1
ubiquitin-dependent protein catabolic process	0.033	0.048	-9999	-0.36	2	2
VEGFR1 homodimer/NRP2	0.023	0.05	-9999	-0.3	5	5

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	0.026	0.046	-9999	-0.21	10	10
HDAC3	0.014	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC4	0.014	0.005	-9999	-10000	0	0
GATA1/HDAC5	0.014	0.005	-9999	-10000	0	0
GATA2/HDAC5	0.01	0.049	-9999	-0.22	11	11
HDAC5/BCL6/BCoR	0.028	0	-9999	-10000	0	0
HDAC9	-0.023	0.12	-9999	-0.37	25	25
Glucocorticoid receptor/Hsp90/HDAC6	0.022	0.039	-9999	-0.24	6	6
HDAC4/ANKRA2	0.018	0.027	-9999	-0.29	2	2
HDAC5/YWHAB	0.02	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.018	0	-9999	-10000	0	0
GATA2	0	0.07	-9999	-0.33	11	11
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	0.027	-9999	-0.42	1	1
HDAC5	0.014	0	-9999	-10000	0	0
GNB1/GNG2	0.009	0.059	-9999	-0.29	10	10
Histones	0.017	0.054	-9999	-0.24	1	1
ADRBK1	0.014	0	-9999	-10000	0	0
HDAC4	0.014	0	-9999	-10000	0	0
XPO1	0.014	0	-9999	-10000	0	0
HDAC5/ANKRA2	0.018	0.027	-9999	-0.29	2	2
HDAC4/Ubc9	0.02	0	-9999	-10000	0	0
HDAC7	0.012	0.027	-9999	-0.42	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	-0.05	0.14	-9999	-0.36	45	45
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	0.005	0.007	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.014	0	-9999	-10000	0	0
NR3C1	0.005	0.059	-9999	-0.42	5	5
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	-0.29	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)	0.028	0	-9999	-10000	0	0
HDAC4/SRF	-0.01	0.087	-9999	-0.24	30	30
HDAC4/ER alpha	0.007	0.061	-9999	-0.27	12	12
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.017	0.054	-9999	-0.24	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	-0.29	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	-0.29	1	1
ESR1	-0.005	0.085	-9999	-0.39	12	12
HDAC6/HDAC11	0.02	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.031	0	-9999	-10000	0	0
NPC	0.008	0	-9999	-10000	0	0
MEF2C	0.005	0.059	-9999	-0.42	5	5
RAN	0.014	0	-9999	-10000	0	0
HDAC4/MEF2C	0.036	0.031	-9999	-0.19	5	5
GNG2	-0.003	0.082	-9999	-0.42	10	10
NCOR2	0.014	0	-9999	-10000	0	0
TUBB2A	0.012	0.027	-9999	-0.42	1	1
HDAC11	0.014	0	-9999	-10000	0	0
HSP90AA1	0.012	0.027	-9999	-0.42	1	1
RANBP2	0.014	0	-9999	-10000	0	0
ANKRA2	0.01	0.037	-9999	-0.42	2	2
RFXANK	0.014	0	-9999	-10000	0	0
nuclear import	-0.027	0	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	0.017	0.068	-9999	-0.24	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	0.022	0.067	-9999	-0.24	15	15
SUMO1	0.014	0	-9999	-10000	0	0
ZFPM1	0.007	0.053	-9999	-0.42	4	4
NPC/RanGAP1/SUMO1/Ubc9	0.018	0	-9999	-10000	0	0
FKBP3	0.014	0	-9999	-10000	0	0
Histones	0.031	0.04	-9999	-10000	0	0
YY1/LSF	0.014	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	0.012	0.055	-9999	-0.2	15	15
I kappa B alpha/HDAC1	0.016	0.042	-9999	-0.2	1	1
SAP18	0.014	0	-9999	-10000	0	0
RELA	0.016	0.053	-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	0.017	0.04	-9999	-10000	0	0
NuRD/MBD3 Complex	0.037	0.021	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.021	0.049	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	0	0.07	-9999	-0.33	11	11
GATA1	0.005	0.007	-9999	-10000	0	0
Mad/Max	0.02	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.041	0.038	-9999	-0.31	2	2
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	0.01	0.044	-9999	-0.16	15	15
KAT2B	0.001	0.074	-9999	-0.42	8	8
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.035	0.013	-9999	-10000	0	0
SIN3 complex	0.035	0.008	-9999	-10000	0	0
SMURF1	0.014	0	-9999	-10000	0	0
CHD3	0.014	0	-9999	-10000	0	0
SAP30	0.013	0.016	-9999	-0.25	1	1
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.014	0	-9999	-10000	0	0
YY1/HDAC3	0.02	0.049	-9999	-0.3	1	1
YY1/HDAC2	0.021	0.038	-9999	-0.19	8	8
YY1/HDAC1	0.02	0.041	-9999	-0.2	9	9
NuRD/MBD2 Complex (MeCP1)	0.039	0.011	-9999	-10000	0	0
PPARG	0.008	0.078	-9999	-0.27	17	17
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	0.04	-9999	-10000	0	0
MBD3L2	0	0.016	-9999	-0.25	1	1
ubiquitin-dependent protein catabolic process	0.026	0.023	-9999	-0.24	2	2
CREBBP	0.014	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.04	0.022	-9999	-10000	0	0
HDAC1	0.012	0.027	-9999	-0.42	1	1
HDAC3	0.01	0.044	-9999	-10000	0	0
HDAC2	0.014	0	-9999	-10000	0	0
YY1	0.017	0.044	-9999	-0.24	8	8
HDAC8	0.014	0	-9999	-10000	0	0
SMAD7	0.012	0.027	-9999	-0.42	1	1
NCOR2	0.014	0	-9999	-10000	0	0
MXD1	0.014	0	-9999	-10000	0	0
STAT3	0.022	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	0.021	0.053	-9999	-0.2	8	8
YY1/SAP30/HDAC1	0.027	0.039	-9999	-0.2	1	1
EP300	0.014	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.022	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.01	0.044	-9999	-0.16	15	15
histone deacetylation	0.039	0.011	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.023	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	0.01	0.052	-9999	-0.2	5	5
GATA1/HDAC1	0.013	0.02	-9999	-0.3	1	1
GATA1/HDAC3	0.011	0.04	-9999	-10000	0	0
CHD4	0.014	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.007	0.08	-9999	-0.22	29	29
SIN3/HDAC complex/Mad/Max	0.039	0.011	-9999	-10000	0	0
NuRD Complex	0.044	0.022	-9999	-10000	0	0
positive regulation of chromatin silencing	0.029	0.039	-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	-0.18	1	1
HDAC complex	0.034	0.015	-9999	-0.21	1	1
GATA1/Fog1	0.009	0.038	-9999	-0.3	4	4
FKBP25/HDAC1/HDAC2	0.027	0.016	-9999	-0.24	1	1
TNF	-0.025	0.11	-9999	-0.34	29	29
negative regulation of cell growth	0.039	0.011	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.039	0.011	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.031	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.015	0.069	-9999	-0.26	15	15
SIN3/HDAC complex/NCoR1	0.037	0.011	-9999	-10000	0	0
TFCP2	0.001	0.071	-9999	-0.4	8	8
NR2C1	0.014	0	-9999	-10000	0	0
MBD3	0.009	0.046	-9999	-0.42	3	3
MBD2	0.014	0	-9999	-10000	0	0

×

Arf6 trafficking 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
SLC2A4	-0.011	0.087	-10000	0	-0.3	21	21
CLTC	0.026	0.005	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.02	0.015	-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	0.023	0.011	-10000	0	-10000	0	0
CPE	0.006	0.04	-10000	0	-0.14	17	17
CTNNB1	0.014	0	-10000	0	-10000	0	0
membrane fusion	0.02	0.016	-10000	0	-10000	0	0
CTNND1	0.025	0	-10000	0	-10000	0	0
DNM2	0.014	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.025	0.008	-10000	0	-10000	0	0
TSHR	-0.01	0.069	-10000	0	-0.18	34	34
INS	0.009	0.003	-10000	0	-10000	0	0
BIN1	-0.011	0.1	-10000	0	-0.42	15	15
mol:Choline	0.02	0.016	-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	0.021	0.018	-10000	0	-10000	0	0
ASAP2/amphiphysin II	0.013	0.055	-10000	0	-0.21	15	15
ARF6/GTP	0.01	0	-10000	0	-10000	0	0
CDH1	-0.033	0.082	-10000	0	-0.22	1	1
clathrin-independent pinocytosis	0.01	0	-10000	0	-10000	0	0
MAPK8IP3	0.009	0.041	-10000	0	-0.36	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	0.032	-10000	0	-0.21	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	0.009	0.06	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.016	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.016	0.024	-10000	0	-0.2	3	3
ACAP1	0.004	0.046	-10000	0	-0.25	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.019	0.008	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.026	0.015	-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	0.032	0.033	-10000	0	-0.21	4	4
RALA/GTP	0.01	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.019	0	-10000	0	-10000	0	0
receptor recycling	0.01	0	-10000	0	-10000	0	0
CTNNA1	0.025	0	-10000	0	-10000	0	0
NME1	0.016	0	-10000	0	-10000	0	0
clathrin coat assembly	0.026	0.005	-10000	0	-10000	0	0
IL2RA	0.004	0.055	-10000	0	-0.22	1	1
VAMP3	0.016	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.009	0.032	-10000	0	-0.18	3	3
EXOC6	0.007	0.053	-10000	0	-0.42	4	4
PLD1	0.016	0.027	-10000	0	-0.24	3	3
PLD2	0.019	0	-10000	0	-10000	0	0
EXOC5	0.012	0.027	-10000	0	-0.42	1	1
PIP5K1C	0.025	0.008	-10000	0	-10000	0	0
SDC1	0.015	0.036	-10000	0	-10000	0	0
ARF6/GDP	0.017	0	-10000	0	-10000	0	0
EXOC7	0.014	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.008	0.062	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.02	0.016	-10000	0	-10000	0	0
endocytosis	-0.012	0.055	0.21	15	-10000	0	15
SCAMP2	0.014	0	-10000	0	-10000	0	0
ADRB2	0.023	0.033	-10000	0	-10000	0	0
EXOC3	0.013	0.016	-10000	0	-0.25	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	0.016	0.046	-10000	0	-10000	0	0
RALA	0.014	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0	0.058	-10000	0	-10000	0	0

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.007	0.021	0.23	2	-10000	0	2
BUB1B	0.015	0.038	-10000	0	-0.29	4	4
PLK1	0.014	0.011	-10000	0	-0.1	1	1
PLK1S1	0.012	0.006	-10000	0	-10000	0	0
KIF2A	0.017	0.017	-10000	0	-0.21	1	1
regulation of mitotic centrosome separation	0.014	0.011	-10000	0	-0.1	1	1
GOLGA2	0.014	0	-10000	0	-10000	0	0
Hec1/SPC24	0.023	0.048	-10000	0	-0.3	5	5
WEE1	0.021	0.009	-10000	0	-10000	0	0
cytokinesis	0.018	0.054	-10000	0	-0.33	4	4
PP2A-alpha B56	0.029	0.066	-10000	0	-0.59	3	3
AURKA	0.012	0.016	-10000	0	-0.23	1	1
PICH/PLK1	0.027	0.029	-10000	0	-0.2	4	4
CENPE	0.002	0.062	-10000	0	-0.22	19	19
RhoA/GTP	0.01	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.017	0.017	-10000	0	-0.2	1	1
PPP2CA	0.014	0	-10000	0	-10000	0	0
FZR1	0.014	0	-10000	0	-10000	0	0
TPX2	0.011	0.026	-10000	0	-0.28	2	2
PAK1	0.011	0.022	-10000	0	-0.25	2	2
SPC24	0.005	0.059	-10000	0	-0.42	5	5
FBXW11	0.014	0	-10000	0	-10000	0	0
CLSPN	0.005	0.054	-10000	0	-0.3	8	8
GORASP1	0.014	0	-10000	0	-10000	0	0
metaphase	0	0.001	-10000	0	-0.015	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.007	0.006	-10000	0	-0.056	1	1
G2 phase of mitotic cell cycle	0	0.001	-10000	0	-0.011	1	1
STAG2	0.009	0.046	-10000	0	-0.42	3	3
GRASP65/GM130/RAB1/GTP	0.021	0.001	-10000	0	-10000	0	0
spindle elongation	0.014	0.011	-10000	0	-0.1	1	1
ODF2	0.013	0.001	-10000	0	-10000	0	0
BUB1	0.015	0.071	-10000	0	-0.65	3	3
TPT1	0.013	0.006	-10000	0	-10000	0	0
CDC25C	0.008	0.055	-10000	0	-0.39	5	5
CDC25B	0.014	0	-10000	0	-10000	0	0
SGOL1	0.007	0.021	-10000	0	-0.23	2	2
RHOA	0.014	0	-10000	0	-10000	0	0
CCNB1/CDK1	0.023	0.007	-10000	0	-10000	0	0
CDC14B	0.009	0.001	-10000	0	-10000	0	0
CDC20	0.009	0.046	-10000	0	-0.42	3	3
PLK1/PBIP1	0.014	0.025	-10000	0	-0.26	2	2
mitosis	0	0.002	0.04	1	-10000	0	1
FBXO5	0.017	0.007	-10000	0	-10000	0	0
CDC2	0.001	0	-10000	0	-10000	0	0
NDC80	0.01	0.037	-10000	0	-0.42	2	2
metaphase plate congression	0.013	0.007	-10000	0	-10000	0	0
ERCC6L	0.026	0.028	-10000	0	-0.19	4	4
NLP/gamma Tubulin	0.011	0.006	-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	-10000	0	-10000	0	0
PPP1R12A	0.009	0.046	-10000	0	-0.42	3	3
interphase	0	0	-10000	0	-10000	0	0
PLK1/PRC1-2	0.026	0.036	-10000	0	-0.35	2	2
GRASP65/GM130/RAB1/GTP/PLK1	0.032	0.009	-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	0.009	-10000	0	-10000	0	0
mitotic prometaphase	0	0.001	-10000	0	-0.01	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.028	0.016	-10000	0	-10000	0	0
microtubule-based process	0.019	0.026	-10000	0	-0.27	2	2
Golgi organization	0.014	0.011	-10000	0	-0.1	1	1
Cohesin/SA2	0.015	0.026	-10000	0	-0.18	4	4
PPP1CB/MYPT1	0.016	0.033	-10000	0	-0.29	3	3
KIF20A	0.01	0.037	-10000	0	-0.42	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	0.014	0.025	-10000	0	-0.26	2	2
PRC1	0.012	0.027	-10000	0	-0.42	1	1
ECT2	0.015	0.033	-10000	0	-0.25	4	4
C13orf34	0.015	0.009	-10000	0	-10000	0	0
NUDC	0.013	0.007	-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	0.013	0.009	-10000	0	-0.083	1	1
spindle stabilization	0.012	0.006	-10000	0	-10000	0	0
APC/C/HCDH1	0.017	0	-10000	0	-10000	0	0
MKLP2/PLK1	0.019	0.027	-10000	0	-0.27	2	2
CCNB1	0.014	0	-10000	0	-10000	0	0
PPP1CB	0.014	0.001	-10000	0	-10000	0	0
BTRC	0.014	0	-10000	0	-10000	0	0
ROCK2	0.01	0.065	-10000	0	-0.38	7	7
TUBG1	0.013	0.006	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.005	-10000	0	-10000	0	0
MLF1IP	0.007	0.027	-10000	0	-0.3	2	2
INCENP	0.014	0.001	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	0.019	0	-9999	-10000	0	0
BAD/BCL-XL/YWHAZ	0.031	0	-9999	-10000	0	0
CDKN1B	0.028	0.011	-9999	-10000	0	0
CDKN1A	0.022	0.036	-9999	-0.28	1	1
FRAP1	0	0	-9999	-10000	0	0
PRKDC	0.014	0	-9999	-10000	0	0
FOXO3	0.028	0.011	-9999	-10000	0	0
AKT1	0.024	0.012	-9999	-10000	0	0
BAD	0.014	0	-9999	-10000	0	0
AKT3	0.014	0.018	-9999	-0.28	1	1
mol:GTP	0	0	-9999	-10000	0	0
FOXO4	0.028	0.011	-9999	-10000	0	0
AKT1/ASK1	0.027	0.023	-9999	-10000	0	0
BAD/YWHAZ	0.028	0	-9999	-10000	0	0
RICTOR	0.007	0.053	-9999	-0.42	4	4
RAF1	0.014	0	-9999	-10000	0	0
JNK cascade	-0.026	0.022	-9999	-10000	0	0
TSC1	0.027	0.017	-9999	-10000	0	0
YWHAZ	0.014	0	-9999	-10000	0	0
AKT1/RAF1	0.031	0.012	-9999	-10000	0	0
EP300	0.014	0	-9999	-10000	0	0
mol:GDP	0.024	0.012	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
TSC2	0.028	0.011	-9999	-10000	0	0
YWHAQ	0.014	0	-9999	-10000	0	0
TBC1D4	0.015	0.027	-9999	-0.23	2	2
MAP3K5	0.008	0.044	-9999	-0.33	4	4
MAPKAP1	0.014	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.023	0.03	-9999	-10000	0	0
YWHAH	0.014	0	-9999	-10000	0	0
AKT1S1	0.028	0.011	-9999	-10000	0	0
CASP9	0.028	0.011	-9999	-10000	0	0
YWHAB	0.014	0	-9999	-10000	0	0
p27Kip1/KPNA1	0.035	0.011	-9999	-10000	0	0
GBL	0	0	-9999	-10000	0	0
PDK1/Src/Hsp90	0.026	0.023	-9999	-0.24	2	2
YWHAE	0.014	0	-9999	-10000	0	0
SRC	0.012	0.027	-9999	-0.42	1	1
AKT2/p21CIP1	0.026	0.035	-9999	-0.27	1	1
KIAA1303	0	0	-9999	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.015	0.005	-9999	-10000	0	0
CHUK	0.027	0.017	-9999	-10000	0	0
BAD/BCL-XL	0.041	0.012	-9999	-10000	0	0
mTORC2	0.014	0.029	-9999	-0.22	4	4
AKT2	0.015	0	-9999	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.034	0.034	-9999	-10000	0	0
PDPK1	0.014	0	-9999	-10000	0	0
MDM2	0.027	0.016	-9999	-10000	0	0
MAPKKK cascade	-0.03	0.012	-9999	-10000	0	0
MDM2/Cbp/p300	0.04	0.016	-9999	-10000	0	0
TSC1/TSC2	0.031	0.016	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.038	0.016	-9999	-10000	0	0
glucose import	0.006	0.05	-9999	-0.21	9	9
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.024	0.01	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	0.006	0.05	-9999	-0.21	9	9
GSK3A	0.027	0.017	-9999	-10000	0	0
FOXO1	0.027	0.017	-9999	-10000	0	0
GSK3B	0.028	0.011	-9999	-10000	0	0
SFN	-0.055	0.13	-9999	-0.28	61	61
G1/S transition of mitotic cell cycle	0.031	0.016	-9999	-10000	0	0
p27Kip1/14-3-3 family	0.023	0.041	-9999	-10000	0	0
PRKACA	0.014	0	-9999	-10000	0	0
KPNA1	0.014	0	-9999	-10000	0	0
HSP90AA1	0.012	0.027	-9999	-0.42	1	1
YWHAG	0.014	0	-9999	-10000	0	0
RHEB	0.014	0	-9999	-10000	0	0
CREBBP	0.014	0	-9999	-10000	0	0

×

HIF-2-alpha transcription factor network

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
MMP14	0.002	0.019	-10000	0	-10000	0	0
oxygen homeostasis	0.007	0.01	-10000	0	-10000	0	0
TCEB2	0.012	0.027	-10000	0	-0.42	1	1
TCEB1	0.014	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	0.069	0.065	-10000	0	-0.25	2	2
EPO	0.11	0.14	-10000	0	-0.48	2	2
FIH (dimer)	0.019	0.028	-10000	0	-0.41	1	1
APEX1	0.021	0.012	-10000	0	-10000	0	0
SERPINE1	0.099	0.17	-10000	0	-0.61	6	6
FLT1	0	0.063	-10000	0	-0.97	1	1
ADORA2A	0.1	0.14	-10000	0	-0.49	3	3
germ cell development	0.11	0.14	-10000	0	-0.5	2	2
SLC11A2	0.11	0.14	-10000	0	-0.46	2	2
BHLHE40	0.11	0.14	-10000	0	-0.47	3	3
HIF1AN	0.019	0.028	-10000	0	-0.41	1	1
HIF2A/ARNT/SIRT1	0.086	0.099	-10000	0	-0.38	1	1
ETS1	0.025	0.018	-10000	0	-0.24	1	1
CITED2	0.002	0.016	-10000	0	-10000	0	0
KDR	-0.001	0.069	-10000	0	-1.1	1	1
PGK1	0.11	0.14	-10000	0	-0.46	2	2
SIRT1	0.011	0.037	-10000	0	-0.42	2	2
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	0.14	0.16	-10000	0	-0.53	2	2
EPAS1	0.062	0.072	-10000	0	-0.28	3	3
SP1	0.02	0.003	-10000	0	-10000	0	0
ABCG2	0.099	0.17	-10000	0	-0.57	4	4
EFNA1	0.11	0.14	-10000	0	-0.46	2	2
FXN	0.1	0.14	-10000	0	-0.46	2	2
POU5F1	0.11	0.14	-10000	0	-0.51	2	2
neuron apoptosis	-0.14	0.16	0.52	2	-10000	0	2
EP300	0.014	0	-10000	0	-10000	0	0
EGLN3	0.01	0.068	-10000	0	-0.39	7	7
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	0.022	0.012	-10000	0	-10000	0	0
SLC2A1	0.1	0.14	-10000	0	-0.46	2	2
TWIST1	0.083	0.18	-10000	0	-0.51	10	10
ELK1	0.02	0.001	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.093	0.095	-10000	0	-0.38	1	1
VEGFA	0.11	0.14	-10000	0	-0.46	2	2
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	0.013	0.021	-9999	-0.2	1	1
SMAD3	0.031	0.021	-9999	-10000	0	0
SMAD3/SMAD4	0.04	0.008	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	0.028	0	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	0.037	0.013	-9999	-10000	0	0
PPM1A	0.014	0	-9999	-10000	0	0
CALM1	0.014	0	-9999	-10000	0	0
SMAD2/SMAD4	0.02	0.018	-9999	-0.18	1	1
MAP3K1	0.004	0.064	-9999	-0.42	6	6
TRAP-1/SMAD4	0.018	0.027	-9999	-0.29	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	0.012	0.027	-9999	-0.42	1	1
KPNB1	0.014	0	-9999	-10000	0	0
TGFBRAP1	0.01	0.037	-9999	-0.42	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	0.014	0	-9999	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.012	0.027	-9999	-0.42	1	1
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
MDM2/SUMO1	0.027	0.012	-9999	-10000	0	0
HDAC4	0.014	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	-0.001	0.01	-9999	-0.16	1	1
SUMO1	0.014	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.014	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.022	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	-0.18	1	1
RANGAP1	0.014	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	0.033	0.021	-9999	-0.21	1	1
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.018	0	-9999	-10000	0	0
Ran/GTP	0.024	0	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.011	0.028	-9999	-0.25	3	3
UBE2I	0.014	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.028	0	-9999	-10000	0	0
NPC	0.008	0	-9999	-10000	0	0
PIAS2	0.012	0.027	-9999	-0.42	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	0.017	0	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.016	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	0.078	-9999	-0.42	9	9
CLTA	0.014	0	-9999	-10000	0	0
mol:GTP	0.001	0	-9999	-10000	0	0
ARFGAP1	0.009	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	0.014	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	0.021	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	0.017	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	0.023	0.036	-9999	-0.17	9	9
PLD2	0.011	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.009	0	-9999	-10000	0	0
PIP5K1A	0.011	0	-9999	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0.018	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	0.009	0	-9999	-10000	0	0
GOSR2	0.013	0	-9999	-10000	0	0
USO1	0.008	0.042	-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	0.019	0.048	-9999	-0.24	9	9

×

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	-0.29	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	0.027	-9999	-0.42	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	0.019	0	-9999	-10000	0	0
regulation of B cell activation	0.018	0	-9999	-10000	0	0

pid_entity	TCGA.GN.A26D	TCGA.GN.A26A	TCGA.GN.A268	TCGA.GN.A267
109_MAP3K5	0.044	-0.0033	-0.19	0.044
47_PPARGC1A	0.014	-0.42	0.014	0.014
105_BMP4	0.014	0.014	0.014	0.014
105_BMP6	0.014	0.014	0.014	0.014
105_BMP7	0.014	0.014	0.014	0.014
105_BMP2	0.014	-0.25	-0.42	0.014
131_RELN/VLDLR	0.035	0.035	0.035	0.035
30_TGFB1/TGF beta receptor Type II	0.02	0.013	0.02	0.013
84_STAT5B	0.039	0.0013	-0.18	0.033
84_STAT5A	0.039	0.0013	-0.18	0.033