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

Pathway.Name	Avg.Num.Perturbations
E-cadherin signaling events	141
Aurora B signaling	118
FOXM1 transcription factor network	95
Signaling events regulated by Ret tyrosine kinase	80
Aurora C signaling	70
Angiopoietin receptor Tie2-mediated signaling	59
TCGA08_p53	57
Signaling events mediated by VEGFR1 and VEGFR2	52
Plasma membrane estrogen receptor signaling	48
p75(NTR)-mediated signaling	47

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
E-cadherin signaling events	0.4638	141	707	5	0.019	0.17	1000	-1000	0.011	-1000
Aurora B signaling	0.3882	118	7968	67	-0.29	0.43	1000	-1000	-0.025	-1000
FOXM1 transcription factor network	0.3125	95	4886	51	0.02	0.5	1000	-1000	-0.12	-1000
Signaling events regulated by Ret tyrosine kinase	0.2632	80	6574	82	-0.22	0.021	1000	-1000	-0.042	-1000
Aurora C signaling	0.2303	70	492	7	0	0.26	1000	-1000	-0.012	-1000
Angiopoietin receptor Tie2-mediated signaling	0.1941	59	5246	88	-0.35	0.07	1000	-1000	-0.05	-1000
TCGA08_p53	0.1875	57	402	7	-0.086	0.026	1000	-1000	-0.011	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.1711	52	6502	125	-0.17	0.043	1000	-1000	-0.037	-1000
Plasma membrane estrogen receptor signaling	0.1579	48	4197	86	-0.25	0.24	1000	-1000	-0.041	-1000
p75(NTR)-mediated signaling	0.1546	47	5963	125	-0.14	0.16	1000	-1000	-0.044	-1000
PLK1 signaling events	0.1546	47	4049	85	-0.076	0.29	1000	-1000	-0.026	-1000
TCGA08_retinoblastoma	0.1546	47	380	8	-0.083	0.27	1000	-1000	-0.004	-1000
HIF-1-alpha transcription factor network	0.1480	45	3461	76	-0.28	0.028	1000	-1000	-0.035	-1000
Endothelins	0.1480	45	4380	96	-0.18	0.19	1000	-1000	-0.046	-1000
IGF1 pathway	0.1447	44	2511	57	-0.1	0.036	1000	-1000	-0.027	-1000
Integrins in angiogenesis	0.1316	40	3401	84	-0.18	0.26	1000	-1000	-0.034	-1000
E-cadherin signaling in the nascent adherens junction	0.1250	38	2916	76	-0.008	0.26	1000	-1000	-0.04	-1000
Glucocorticoid receptor regulatory network	0.1217	37	4314	114	-0.28	0.39	1000	-1000	-0.047	-1000
PDGFR-alpha signaling pathway	0.1184	36	1593	44	-0.095	0.023	1000	-1000	-0.027	-1000
Reelin signaling pathway	0.1151	35	1970	56	-0.084	0.047	1000	-1000	-0.027	-1000
Nongenotropic Androgen signaling	0.1151	35	1835	52	-0.13	0.087	1000	-1000	-0.024	-1000
Signaling events mediated by the Hedgehog family	0.1053	32	1704	52	-0.12	0.072	1000	-1000	-0.024	-1000
Syndecan-1-mediated signaling events	0.1020	31	1054	34	-0.016	0.1	1000	-1000	-0.024	-1000
IL23-mediated signaling events	0.1020	31	1868	60	-0.013	0.37	1000	-1000	-0.082	-1000
Syndecan-2-mediated signaling events	0.0954	29	2059	69	-0.038	0.17	1000	-1000	-0.028	-1000
Aurora A signaling	0.0954	29	1778	60	-0.065	0.28	1000	-1000	-0.017	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0954	29	3487	120	-0.18	0.16	1000	-1000	-0.037	-1000
Cellular roles of Anthrax toxin	0.0921	28	1102	39	-0.095	0.023	1000	-1000	-0.016	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0855	26	1932	74	-0.14	0.26	1000	-1000	-0.045	-1000
E-cadherin signaling in keratinocytes	0.0855	26	1150	43	-0.073	0.26	1000	-1000	-0.023	-1000
LPA4-mediated signaling events	0.0822	25	310	12	-0.081	0	1000	-1000	-0.015	-1000
Coregulation of Androgen receptor activity	0.0822	25	1963	76	-0.069	0.27	1000	-1000	-0.018	-1000
Thromboxane A2 receptor signaling	0.0789	24	2579	105	-0.14	0.042	1000	-1000	-0.036	-1000
IL4-mediated signaling events	0.0789	24	2222	91	-0.6	0.36	1000	-1000	-0.13	-1000
Glypican 1 network	0.0789	24	1160	48	-0.089	0.065	1000	-1000	-0.021	-1000
HIF-2-alpha transcription factor network	0.0789	24	1061	43	-0.36	0.15	1000	-1000	-0.041	-1000
Effects of Botulinum toxin	0.0789	24	644	26	-0.11	0.039	1000	-1000	-0.012	-1000
amb2 Integrin signaling	0.0757	23	1926	82	-0.12	0.099	1000	-1000	-0.024	-1000
IL1-mediated signaling events	0.0757	23	1435	62	-0.024	0.23	1000	-1000	-0.034	-1000
Nectin adhesion pathway	0.0691	21	1362	63	-0.076	0.26	1000	-1000	-0.032	-1000
Fc-epsilon receptor I signaling in mast cells	0.0658	20	1984	97	-0.073	0.035	1000	-1000	-0.051	-1000
BMP receptor signaling	0.0625	19	1555	81	-0.23	0.083	1000	-1000	-0.017	-1000
Canonical Wnt signaling pathway	0.0625	19	1012	51	-0.37	0.18	1000	-1000	-0.031	-1000
S1P3 pathway	0.0625	19	804	42	-0.077	0.035	1000	-1000	-0.036	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0625	19	1491	78	-0.11	0.039	1000	-1000	-0.052	-1000
S1P5 pathway	0.0592	18	311	17	-0.05	0.11	1000	-1000	-0.009	-1000
TCR signaling in naïve CD8+ T cells	0.0592	18	1680	93	-0.04	0.034	1000	-1000	-0.037	-1000
EPHB forward signaling	0.0592	18	1559	85	-0.063	0.06	1000	-1000	-0.039	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0592	18	605	33	-0.11	0.27	1000	-1000	-0.023	-1000
Arf6 signaling events	0.0559	17	1067	62	-0.094	0.036	1000	-1000	-0.046	-1000
S1P1 pathway	0.0559	17	622	36	-0.072	0.02	1000	-1000	-0.035	-1000
S1P4 pathway	0.0559	17	432	25	-0.05	0.11	1000	-1000	-0.017	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0526	16	465	28	-0.066	0.11	1000	-1000	-0.017	-1000
LPA receptor mediated events	0.0493	15	1554	102	-0.092	0.12	1000	-1000	-0.053	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0461	14	799	54	-0.084	0.033	1000	-1000	-0.034	-1000
Signaling events mediated by PTP1B	0.0461	14	1130	76	-0.14	0.064	1000	-1000	-0.024	-1000
FOXA2 and FOXA3 transcription factor networks	0.0461	14	682	46	-0.16	0.26	1000	-1000	-0.078	-1000
mTOR signaling pathway	0.0461	14	754	53	-0.032	0.045	1000	-1000	-0.028	-1000
BCR signaling pathway	0.0461	14	1406	99	-0.06	0.04	1000	-1000	-0.046	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0428	13	461	34	-0.016	0.03	1000	-1000	-0.022	-1000
Hedgehog signaling events mediated by Gli proteins	0.0428	13	892	65	-0.14	0.047	1000	-1000	-0.029	-1000
Presenilin action in Notch and Wnt signaling	0.0428	13	844	61	-0.045	0.18	1000	-1000	-0.035	-1000
EGFR-dependent Endothelin signaling events	0.0395	12	257	21	-0.028	0.04	1000	-1000	-0.03	-1000
Insulin Pathway	0.0395	12	934	74	-0.096	0.07	1000	-1000	-0.036	-1000
PDGFR-beta signaling pathway	0.0395	12	1227	97	-0.031	0.041	1000	-1000	-0.038	-1000
ErbB2/ErbB3 signaling events	0.0362	11	771	65	-0.031	0.066	1000	-1000	-0.049	-1000
Noncanonical Wnt signaling pathway	0.0362	11	300	26	-0.068	0.02	1000	-1000	-0.024	-1000
ErbB4 signaling events	0.0329	10	748	69	-0.11	0.14	1000	-1000	-0.028	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0329	10	850	85	-0.052	0.028	1000	-1000	-0.035	-1000
Insulin-mediated glucose transport	0.0329	10	333	32	-0.037	0.28	1000	-1000	-0.024	-1000
Class I PI3K signaling events mediated by Akt	0.0329	10	742	68	-0.057	0.28	1000	-1000	-0.024	-1000
Ephrin B reverse signaling	0.0296	9	451	48	-0.026	0.026	1000	-1000	-0.026	-1000
Syndecan-3-mediated signaling events	0.0296	9	340	35	-0.099	0.17	1000	-1000	-0.025	-1000
Signaling mediated by p38-alpha and p38-beta	0.0296	9	435	44	-0.06	0.045	1000	-1000	-0.021	-1000
Calcium signaling in the CD4+ TCR pathway	0.0296	9	282	31	-0.011	0.08	1000	-1000	-0.039	-1000
Syndecan-4-mediated signaling events	0.0296	9	621	67	-0.17	0.061	1000	-1000	-0.027	-1000
EPO signaling pathway	0.0263	8	476	55	-0.034	0.033	1000	-1000	-0.03	-1000
FAS signaling pathway (CD95)	0.0263	8	408	47	-0.021	0.05	1000	-1000	-0.028	-1000
Wnt signaling	0.0263	8	62	7	-0.025	0.019	1000	-1000	-0.01	-1000
Regulation of Telomerase	0.0263	8	883	102	-0.24	0.085	1000	-1000	-0.033	-1000
Regulation of Androgen receptor activity	0.0263	8	584	70	-0.066	0.14	1000	-1000	-0.041	-1000
IL12-mediated signaling events	0.0230	7	650	87	-0.06	0.074	1000	-1000	-0.068	-1000
IFN-gamma pathway	0.0230	7	509	68	-0.074	0.075	1000	-1000	-0.037	-1000
Ceramide signaling pathway	0.0230	7	571	76	-0.079	0.055	1000	-1000	-0.031	-1000
ceramide signaling pathway	0.0230	7	347	49	-0.017	0.038	1000	-1000	-0.026	-1000
TCGA08_rtk_signaling	0.0230	7	184	26	-0.049	0.047	1000	-1000	-0.008	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0230	7	491	68	-0.043	0.19	1000	-1000	-0.06	-1000
Regulation of nuclear SMAD2/3 signaling	0.0197	6	869	136	-0.12	0.056	1000	-1000	-0.032	-1000
Osteopontin-mediated events	0.0197	6	252	38	-0.058	0.034	1000	-1000	-0.033	-1000
Visual signal transduction: Rods	0.0197	6	352	52	-0.017	0.086	1000	-1000	-0.03	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0164	5	421	83	-0.021	0.28	1000	-1000	-0.018	-1000
FoxO family signaling	0.0164	5	324	64	-0.027	0.28	1000	-1000	-0.052	-1000
Regulation of p38-alpha and p38-beta	0.0164	5	306	54	-0.055	0.064	1000	-1000	-0.04	-1000
Caspase cascade in apoptosis	0.0132	4	348	74	-0.019	0.12	1000	-1000	-0.033	-1000
Visual signal transduction: Cones	0.0132	4	179	38	-0.017	0.039	1000	-1000	-0.02	-1000
Signaling mediated by p38-gamma and p38-delta	0.0132	4	63	15	-0.015	0.02	1000	-1000	-0.023	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0132	4	181	45	-0.024	0.048	1000	-1000	-0.033	-1000
IL27-mediated signaling events	0.0132	4	216	51	-0.018	0.062	1000	-1000	-0.045	-1000
Signaling events mediated by PRL	0.0132	4	141	34	-0.049	0.035	1000	-1000	-0.037	-1000
Ras signaling in the CD4+ TCR pathway	0.0132	4	70	17	-0.013	0.031	1000	-1000	-0.023	-1000
Signaling events mediated by HDAC Class II	0.0099	3	298	75	-0.082	0.038	1000	-1000	-0.022	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0099	3	177	52	-0.01	0.057	1000	-1000	-0.027	-1000
Retinoic acid receptors-mediated signaling	0.0099	3	178	58	-0.019	0.04	1000	-1000	-0.028	-1000
Class I PI3K signaling events	0.0099	3	260	73	-0.029	0.064	1000	-1000	-0.027	-1000
VEGFR1 specific signals	0.0099	3	175	56	-0.03	0.031	1000	-1000	-0.031	-1000
p38 MAPK signaling pathway	0.0099	3	167	44	-0.033	0.046	1000	-1000	-0.017	-1000
Canonical NF-kappaB pathway	0.0066	2	92	39	-0.02	0.041	1000	-1000	-0.02	-1000
BARD1 signaling events	0.0066	2	114	57	-0.031	0.048	1000	-1000	-0.039	-1000
JNK signaling in the CD4+ TCR pathway	0.0066	2	42	17	-0.01	0.053	1000	-1000	-0.022	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0066	2	97	37	-0.029	0.049	1000	-1000	-0.02	-1000
TRAIL signaling pathway	0.0066	2	108	48	-0.019	0.035	1000	-1000	-0.021	-1000
IL2 signaling events mediated by PI3K	0.0066	2	166	58	-0.014	0.047	1000	-1000	-0.037	-1000
IL6-mediated signaling events	0.0066	2	213	75	-0.11	0.05	1000	-1000	-0.051	-1000
IL2 signaling events mediated by STAT5	0.0066	2	54	22	-0.032	0.031	1000	-1000	-0.026	-1000
Arf6 trafficking events	0.0066	2	154	71	-0.077	0.067	1000	-1000	-0.029	-1000
Rapid glucocorticoid signaling	0.0066	2	46	20	-0.017	0.026	1000	-1000	-0.01	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0033	1	27	23	-0.009	0.037	1000	-1000	-0.015	-1000
Ephrin A reverse signaling	0.0033	1	9	7	-0.019	0.025	1000	-1000	-0.012	-1000
Signaling events mediated by HDAC Class III	0.0033	1	53	40	-0.038	0.038	1000	-1000	-0.03	-1000
Signaling events mediated by HDAC Class I	0.0033	1	144	104	-0.037	0.05	1000	-1000	-0.037	-1000
Glypican 2 network	0.0033	1	6	4	0.02	0.029	1000	-1000	0.012	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0033	1	31	27	-0.021	0.045	1000	-1000	-0.026	-1000
Class IB PI3K non-lipid kinase events	0.0033	1	3	3	-0.021	0.021	1000	-1000	-0.011	-1000
Arf1 pathway	0.0033	1	63	54	-0.011	0.026	1000	-1000	-0.014	-1000
PLK2 and PLK4 events	0.0000	0	0	3	-0.017	0.02	1000	-1000	-0.021	-1000
Circadian rhythm pathway	0.0000	0	5	22	-0.009	0.04	1000	-1000	-0.025	-1000
a4b1 and a4b7 Integrin signaling	0.0000	0	0	5	0.02	0.029	1000	-1000	0.013	-1000
Arf6 downstream pathway	0.0000	0	7	43	-0.04	0.042	1000	-1000	-0.023	-1000
Paxillin-dependent events mediated by a4b1	0.0000	0	30	36	-0.036	0.038	1000	-1000	-0.024	-1000
Atypical NF-kappaB pathway	0.0000	0	10	31	-0.02	0.024	1000	-1000	-0.02	-1000
Alternative NF-kappaB pathway	0.0000	0	0	13	0	0.053	1000	-1000	0	-1000
Total	NA	2405	146559	7203	-10	13	131000	-131000	-4	-131000

E-cadherin signaling events

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.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.16	0.08	0.21	226	-9999	226
E-cadherin/beta catenin	0.17	0.082	0.22	230	-9999	230
CTNNB1	0.019	0.006	-10000	0	-9999	0
JUP	0.02	0.003	-10000	0	-9999	0
CDH1	0.26	0.097	0.29	251	-9999	251

×

Aurora B 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.17	0.11	0.23	206	-0.25	1	207
STMN1	0.12	0.052	0.14	254	-10000	0	254
Aurora B/RasGAP/Survivin	0.32	0.13	0.37	250	-10000	0	250
Chromosomal passenger complex/Cul3 protein complex	0.12	0.084	0.18	186	-0.15	1	187
BIRC5	0.28	0.073	0.3	273	-10000	0	273
DES	-0.29	0.15	-10000	0	-0.53	39	39
Aurora C/Aurora B/INCENP	0.17	0.08	0.21	235	-0.098	1	236
Aurora B/TACC1	0.16	0.073	0.19	241	-0.15	1	242
Aurora B/PP2A	0.18	0.076	0.22	246	-10000	0	246
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	0.054	0.025	0.13	11	-10000	0	11
mitotic metaphase/anaphase transition	-0.009	0.006	-10000	0	-10000	0	0
NDC80	0.12	0.061	0.15	251	-10000	0	251
Cul3 protein complex	0.003	0.078	-10000	0	-0.17	47	47
KIF2C	0.18	0.076	0.21	236	-10000	0	236
PEBP1	0.024	0.003	-10000	0	-10000	0	0
KIF20A	0.27	0.067	0.29	275	-10000	0	275
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.18	0.076	0.22	246	-10000	0	246
SEPT1	0.02	0.002	-10000	0	-10000	0	0
SMC2	0.02	0.003	-10000	0	-10000	0	0
SMC4	0.014	0.01	-10000	0	-10000	0	0
NSUN2/NPM1/Nucleolin	0.15	0.18	0.28	59	-0.42	22	81
PSMA3	0.02	0.003	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.006	0.005	-10000	0	-10000	0	0
H3F3B	0.12	0.049	0.13	254	-10000	0	254
AURKB	0.26	0.099	0.3	255	-10000	0	255
AURKC	0.019	0.019	-10000	0	-0.29	1	1
CDCA8	0.21	0.13	0.31	195	-10000	0	195
cytokinesis	0.18	0.099	0.23	219	-10000	0	219
Aurora B/Septin1	0.26	0.12	0.31	244	-10000	0	244
AURKA	0.003	0.064	0.29	13	-10000	0	13
INCENP	0.033	0.006	-10000	0	-10000	0	0
KLHL13	-0.029	0.11	-10000	0	-0.29	47	47
BUB1	0.17	0.15	0.29	176	-10000	0	176
hSgo1/Aurora B/Survivin	0.42	0.19	0.49	246	-10000	0	246
EVI5	0.031	0.005	-10000	0	-10000	0	0
RhoA/GTP	0.18	0.094	0.24	191	-10000	0	191
SGOL1	0.26	0.098	0.29	251	-10000	0	251
CENPA	0.22	0.094	0.25	260	-10000	0	260
NCAPG	0.24	0.11	0.29	240	-10000	0	240
Aurora B/HC8 Proteasome	0.19	0.075	0.22	248	-10000	0	248
NCAPD2	0.019	0.005	-10000	0	-10000	0	0
Aurora B/PP1-gamma	0.19	0.069	0.22	255	-10000	0	255
RHOA	0.019	0.006	-10000	0	-10000	0	0
NCAPH	0.22	0.12	0.29	208	-10000	0	208
NPM1	0.12	0.12	0.2	6	-0.46	9	15
RASA1	0.02	0.004	-10000	0	-10000	0	0
KLHL9	0.02	0.004	-10000	0	-10000	0	0
mitotic prometaphase	0.002	0.002	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.18	0.075	0.22	248	-10000	0	248
PPP1CC	0.021	0.001	-10000	0	-10000	0	0
Centraspindlin	0.21	0.093	0.25	239	-10000	0	239
RhoA/GDP	0.014	0.004	-10000	0	-10000	0	0
NSUN2	0.14	0.099	0.23	54	-0.32	6	60
MYLK	0.007	0.13	0.16	110	-0.13	120	230
KIF23	0.031	0.006	-10000	0	-10000	0	0
VIM	0.12	0.064	0.14	243	-0.14	5	248
RACGAP1	0.031	0.006	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
NCL	0.11	0.13	0.18	12	-0.46	11	23
Chromosomal passenger complex	0.25	0.085	0.27	268	-10000	0	268
Chromosomal passenger complex/EVI5	0.43	0.18	0.49	252	-10000	0	252
TACC1	0.018	0.019	-10000	0	-0.29	1	1
PPP2R5D	0.02	0.004	-10000	0	-10000	0	0
CUL3	0.019	0.006	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	0.4	0.38	0.76	110	-0.9	2	112
PLK1	0.21	0.17	0.55	27	-10000	0	27
BIRC5	0.34	0.14	0.45	108	-0.65	2	110
HSPA1B	0.41	0.39	0.77	110	-0.91	2	112
MAP2K1	0.1	0.095	0.22	86	-10000	0	86
BRCA2	0.4	0.38	0.76	111	-0.91	2	113
FOXM1	0.45	0.43	0.83	123	-1.1	2	125
XRCC1	0.4	0.39	0.77	110	-0.91	2	112
FOXM1B/p19	0.3	0.37	0.69	87	-0.97	3	90
Cyclin D1/CDK4	0.35	0.36	0.69	110	-0.84	2	112
CDC2	0.42	0.4	0.78	123	-0.96	2	125
TGFA	0.36	0.36	0.69	122	-0.81	2	124
SKP2	0.43	0.39	0.78	122	-0.91	2	124
CCNE1	0.036	0.042	0.31	4	-10000	0	4
CKS1B	0.4	0.38	0.73	123	-0.91	2	125
RB1	0.21	0.25	0.5	88	-0.58	1	89
FOXM1C/SP1	0.36	0.36	0.73	88	-1.1	2	90
AURKB	0.29	0.23	0.44	110	-0.71	9	119
CENPF	0.44	0.41	0.8	123	-0.91	2	125
CDK4	0.052	0.042	0.17	5	-10000	0	5
MYC	0.32	0.35	0.65	111	-0.94	3	114
CHEK2	0.11	0.096	0.22	89	-10000	0	89
ONECUT1	0.36	0.36	0.7	116	-0.88	2	118
CDKN2A	0.18	0.11	0.23	234	-0.15	9	243
LAMA4	0.33	0.5	0.75	111	-1	17	128
FOXM1B/HNF6	0.37	0.38	0.74	99	-0.99	2	101
FOS	0.35	0.46	0.76	109	-0.94	11	120
SP1	0.02	0.009	-10000	0	-0.11	1	1
CDC25B	0.41	0.38	0.76	112	-0.91	2	114
response to radiation	0.073	0.069	0.17	75	-10000	0	75
CENPB	0.41	0.38	0.76	111	-0.91	2	113
CENPA	0.47	0.4	0.86	107	-0.98	1	108
NEK2	0.5	0.4	0.84	131	-0.91	1	132
HIST1H2BA	0.4	0.38	0.76	109	-0.91	2	111
CCNA2	0.035	0.036	0.32	2	-10000	0	2
EP300	0.02	0.003	-10000	0	-10000	0	0
CCNB1/CDK1	0.4	0.4	0.82	91	-1	2	93
CCNB2	0.48	0.39	0.82	131	-0.84	2	133
CCNB1	0.42	0.4	0.8	112	-0.96	2	114
ETV5	0.47	0.4	0.8	136	-0.86	1	137
ESR1	0.14	0.6	0.76	100	-0.94	21	121
CCND1	0.35	0.37	0.71	114	-0.85	2	116
GSK3A	0.084	0.077	0.18	75	-10000	0	75
Cyclin A-E1/CDK1-2	0.1	0.086	0.22	67	-10000	0	67
CDK2	0.033	0.027	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.092	0.086	0.18	111	-10000	0	111
FOXM1B/Cbp/p300	0.29	0.33	0.66	68	-0.97	2	70
GAS1	0.068	0.63	0.76	98	-0.96	26	124
MMP2	0.36	0.46	0.75	111	-1	11	122
RB1/FOXM1C	0.32	0.35	0.67	103	-0.9	2	105
CREBBP	0.02	0.004	-10000	0	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.048	0.099	-10000	0	-0.41	18	18
Crk/p130 Cas/Paxillin	-0.15	0.089	-10000	0	-0.22	165	165
JUN	-0.1	0.091	-10000	0	-0.28	19	19
HRAS	0.02	0.005	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.1	0.098	-10000	0	-0.17	187	187
RAP1A	0.021	0.002	-10000	0	-10000	0	0
FRS2	0.02	0.003	-10000	0	-10000	0	0
RAP1A/GDP	0.015	0.001	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.098	0.098	-10000	0	-0.17	184	184
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.021	0.001	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.019	0.006	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.094	0.084	-10000	0	-0.16	189	189
RHOA	0.019	0.006	-10000	0	-10000	0	0
RAP1A/GTP	-0.092	0.089	-10000	0	-0.16	189	189
GRB7	0.021	0.023	0.29	2	-10000	0	2
RET51/GFRalpha1/GDNF	-0.099	0.097	-10000	0	-0.17	184	184
MAPKKK cascade	-0.11	0.082	-10000	0	-0.19	139	139
BCAR1	0.02	0.004	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.098	0.088	-10000	0	-0.16	189	189
lamellipodium assembly	-0.14	0.086	-10000	0	-0.22	123	123
RET51/GFRalpha1/GDNF/SHC	-0.092	0.098	-10000	0	-0.17	172	172
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.086	0.085	-10000	0	-0.16	172	172
RET9/GFRalpha1/GDNF/Shank3	-0.094	0.084	-10000	0	-0.16	189	189
MAPK3	-0.097	0.085	0.2	2	-0.26	10	12
DOK1	0.02	0.003	-10000	0	-10000	0	0
DOK6	0.011	0.051	-10000	0	-0.29	8	8
PXN	0.021	0.001	-10000	0	-10000	0	0
neurite development	-0.1	0.078	-10000	0	-0.25	16	16
DOK5	0.013	0.044	0.29	1	-0.29	5	6
GFRA1	-0.22	0.13	-10000	0	-0.29	228	228
MAPK8	-0.095	0.097	-10000	0	-0.19	146	146
HRAS/GTP	-0.11	0.1	-10000	0	-0.2	146	146
tube development	-0.089	0.082	0.19	1	-0.15	183	184
MAPK1	-0.097	0.087	0.17	8	-0.26	10	18
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.11	0.088	-10000	0	-0.18	181	181
Rac1/GDP	0.015	0.002	-10000	0	-10000	0	0
SRC	0.019	0.006	-10000	0	-10000	0	0
PDLIM7	0.02	0.004	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.092	0.1	-10000	0	-0.17	176	176
SHC1	0.019	0.006	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.1	0.097	-10000	0	-0.17	189	189
RET51/GFRalpha1/GDNF/Dok5	-0.096	0.1	0.21	1	-0.17	177	178
PRKCA	0.014	0.044	-10000	0	-0.29	6	6
HRAS/GDP	0.015	0.003	-10000	0	-10000	0	0
CREB1	-0.13	0.13	-10000	0	-0.24	163	163
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.1	0.092	-10000	0	-0.18	167	167
RET51/GFRalpha1/GDNF/Grb7	-0.097	0.096	-10000	0	-0.17	181	181
mol:GDP	0	0	-10000	0	-10000	0	0
RET	0.007	0.062	-10000	0	-0.29	12	12
DOK4	0.02	0.004	-10000	0	-10000	0	0
JNK cascade	-0.1	0.089	-10000	0	-0.28	19	19
RET9/GFRalpha1/GDNF/FRS2	-0.093	0.085	-10000	0	-0.16	186	186
SHANK3	0.02	0.004	-10000	0	-10000	0	0
RASA1	0.02	0.004	-10000	0	-10000	0	0
NCK1	0.015	0.009	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.097	0.09	-10000	0	-0.18	162	162
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.12	0.098	-10000	0	-0.19	187	187
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.097	0.1	-10000	0	-0.19	150	150
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.11	0.1	-10000	0	-0.19	163	163
PI3K	-0.18	0.13	-10000	0	-0.3	126	126
SOS1	0.02	0.003	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.087	0.084	-10000	0	-0.15	183	183
GRB10	0.019	0.018	-10000	0	-0.29	1	1
activation of MAPKK activity	-0.11	0.089	-10000	0	-0.26	13	13
RET51/GFRalpha1/GDNF/FRS2	-0.1	0.097	-10000	0	-0.17	186	186
GAB1	0.02	0.003	-10000	0	-10000	0	0
IRS1	0.008	0.056	-10000	0	-0.29	10	10
IRS2	0.011	0.051	-10000	0	-0.29	8	8
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.11	0.11	-10000	0	-0.2	167	167
RET51/GFRalpha1/GDNF/PKC alpha	-0.1	0.098	-10000	0	-0.17	185	185
GRB2	0.02	0.005	-10000	0	-10000	0	0
PRKACA	0.02	0.004	-10000	0	-10000	0	0
GDNF	-0.004	0.017	-10000	0	-10000	0	0
RAC1	0.02	0.003	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.1	0.1	-10000	0	-0.17	189	189
Rac1/GTP	-0.16	0.1	-10000	0	-0.25	123	123
RET9/GFRalpha1/GDNF	-0.1	0.087	-10000	0	-0.17	189	189
GFRalpha1/GDNF	-0.13	0.1	-10000	0	-0.2	189	189

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.02	0.003	-10000	0	-10000	0	0
Aurora C/Aurora B/INCENP	0.16	0.076	0.2	235	-0.1	1	236
metaphase	0	0	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
H3F3B	0.021	0.012	-10000	0	-10000	0	0
AURKB	0.26	0.096	0.29	255	-10000	0	255
AURKC	0.019	0.019	-10000	0	-0.29	1	1

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.27	0.41	-10000	0	-0.84	95	95
NCK1/PAK1/Dok-R	-0.14	0.18	-10000	0	-0.39	96	96
NCK1/Dok-R	-0.27	0.44	-10000	0	-0.86	95	95
PIK3CA	0.014	0.01	-10000	0	-10000	0	0
mol:beta2-estradiol	0.028	0.068	0.23	28	-10000	0	28
RELA	0.02	0.003	-10000	0	-10000	0	0
SHC1	0.007	0.018	-10000	0	-10000	0	0
Rac/GDP	0.015	0.002	-10000	0	-10000	0	0
F2	0.021	0.08	0.26	27	-10000	0	27
TNIP2	0.019	0.006	-10000	0	-10000	0	0
NF kappa B/RelA	-0.26	0.44	-10000	0	-0.85	95	95
FN1	0.01	0.051	-10000	0	-0.29	8	8
PLD2	-0.3	0.47	-10000	0	-0.94	94	94
PTPN11	0.021	0.001	-10000	0	-10000	0	0
GRB14	0.07	0.11	0.29	54	-10000	0	54
ELK1	-0.29	0.43	-10000	0	-0.88	95	95
GRB7	0.021	0.023	0.29	2	-10000	0	2
PAK1	0.019	0.005	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.27	0.46	-10000	0	-0.89	95	95
CDKN1A	-0.19	0.29	-10000	0	-0.6	95	95
ITGA5	0.018	0.026	-10000	0	-0.29	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.28	0.46	-10000	0	-0.9	95	95
CRK	0.019	0.006	-10000	0	-10000	0	0
mol:NO	-0.2	0.3	-10000	0	-0.63	95	95
PLG	-0.31	0.47	-10000	0	-0.94	95	95
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.26	0.38	-10000	0	-0.8	95	95
GRB2	0.02	0.005	-10000	0	-10000	0	0
PIK3R1	0.008	0.018	-10000	0	-10000	0	0
ANGPT2	-0.14	0.26	-10000	0	-0.72	36	36
BMX	-0.35	0.48	-10000	0	-1	94	94
ANGPT1	-0.13	0.32	-10000	0	-1.1	27	27
tube development	-0.22	0.32	-10000	0	-0.66	96	96
ANGPT4	0.006	0.018	-10000	0	-10000	0	0
response to hypoxia	-0.021	0.029	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.28	0.5	-10000	0	-0.95	96	96
alpha5/beta1 Integrin	0.028	0.02	-10000	0	-0.2	2	2
FGF2	-0.073	0.14	-10000	0	-0.29	88	88
STAT5A (dimer)	-0.24	0.37	-10000	0	-0.75	95	95
mol:L-citrulline	-0.2	0.3	-10000	0	-0.63	95	95
AGTR1	-0.093	0.14	-10000	0	-0.29	99	99
MAPK14	-0.34	0.52	-10000	0	-1.1	95	95
Tie2/SHP2	-0.28	0.45	-10000	0	-0.92	91	91
TEK	-0.31	0.48	-10000	0	-1	91	91
RPS6KB1	-0.26	0.4	-10000	0	-0.81	95	95
Angiotensin II/AT1	-0.06	0.097	-10000	0	-0.2	99	99
Tie2/Ang1/GRB2	-0.3	0.49	-10000	0	-0.95	96	96
MAPK3	-0.29	0.43	-10000	0	-0.88	94	94
MAPK1	-0.29	0.43	-10000	0	-0.88	94	94
Tie2/Ang1/GRB7	-0.3	0.49	-10000	0	-0.95	96	96
NFKB1	0.02	0.003	-10000	0	-10000	0	0
MAPK8	-0.31	0.47	-10000	0	-0.94	96	96
PI3K	-0.32	0.47	-10000	0	-0.97	95	95
FES	-0.34	0.52	-10000	0	-1.1	95	95
Crk/Dok-R	-0.28	0.46	-10000	0	-0.9	95	95
Tie2/Ang1/ABIN2	-0.3	0.49	-10000	0	-0.95	96	96
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.24	0.36	-10000	0	-0.75	95	95
STAT5A	0.02	0.002	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.26	0.39	-10000	0	-0.8	95	95
Tie2/Ang2	-0.29	0.44	-10000	0	-0.89	95	95
Tie2/Ang1	-0.32	0.51	-10000	0	-1	95	95
FOXO1	-0.24	0.37	-10000	0	-0.75	95	95
ELF1	-0.018	0.062	-10000	0	-0.12	74	74
ELF2	-0.3	0.47	-10000	0	-0.94	94	94
mol:Choline	-0.29	0.44	-10000	0	-0.9	94	94
cell migration	-0.08	0.1	-10000	0	-0.22	96	96
FYN	-0.25	0.36	-10000	0	-0.75	96	96
DOK2	0.019	0.006	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.17	0.27	-10000	0	-0.54	95	95
ETS1	-0.012	0.071	-10000	0	-0.25	22	22
PXN	-0.21	0.33	-10000	0	-0.67	95	95
ITGB1	0.02	0.003	-10000	0	-10000	0	0
NOS3	-0.23	0.35	-10000	0	-0.72	95	95
RAC1	0.02	0.003	-10000	0	-10000	0	0
TNF	-0.015	0.082	0.28	3	-0.24	26	29
MAPKKK cascade	-0.29	0.44	-10000	0	-0.9	94	94
RASA1	0.02	0.004	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.3	0.49	-10000	0	-0.95	96	96
NCK1	0.015	0.009	-10000	0	-10000	0	0
vasculogenesis	-0.18	0.27	-10000	0	-0.56	95	95
mol:Phosphatidic acid	-0.29	0.44	-10000	0	-0.9	94	94
mol:Angiotensin II	0	0.002	-10000	0	-10000	0	0
mol:NADP	-0.2	0.3	-10000	0	-0.63	95	95
Rac1/GTP	-0.24	0.37	-10000	0	-0.76	95	95
MMP2	-0.31	0.48	-10000	0	-0.95	95	95

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	0.13	0.043	0.14	270	-10000	0	270
TP53	0.026	0.062	-10000	0	-0.12	40	40
Senescence	0.026	0.061	-10000	0	-0.12	40	40
Apoptosis	0.026	0.061	-10000	0	-0.12	40	40
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	-0.086	0.052	0.2	7	-0.18	5	12
MDM4	0.019	0.005	-10000	0	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	0.003	0.073	-10000	0	-0.2	33	33
AKT1	-0.11	0.21	0.24	3	-0.42	80	83
PTK2B	-0.14	0.19	0.32	1	-0.43	84	85
VEGFR2 homodimer/Frs2	-0.15	0.21	-10000	0	-0.47	85	85
CAV1	-0.008	0.088	-10000	0	-0.29	26	26
CALM1	0.02	0.005	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.11	0.21	-10000	0	-0.43	85	85
endothelial cell proliferation	-0.1	0.21	0.32	10	-0.4	84	94
mol:Ca2+	-0.13	0.18	0.17	4	-0.4	84	88
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.093	0.21	-10000	0	-0.42	83	83
RP11-342D11.1	-0.13	0.18	0.16	4	-0.4	85	89
CDH5	0.013	0.048	-10000	0	-0.29	7	7
VEGFA homodimer	0.043	0.021	-10000	0	-10000	0	0
SHC1	0.019	0.006	-10000	0	-10000	0	0
SHC2	0.007	0.062	-10000	0	-0.29	12	12
HRAS/GDP	-0.13	0.16	-10000	0	-0.37	80	80
SH2D2A	0.028	0.048	0.29	9	-10000	0	9
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.098	0.21	0.25	2	-0.4	85	87
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.1	0.21	0.2	3	-0.43	85	88
VEGFR1 homodimer	0.019	0.019	-10000	0	-0.29	1	1
SHC/GRB2/SOS1	-0.083	0.2	-10000	0	-0.39	85	85
GRB10	-0.13	0.18	0.17	4	-0.42	80	84
PTPN11	0.021	0.001	-10000	0	-10000	0	0
GRB2	0.02	0.005	-10000	0	-10000	0	0
PAK1	0.019	0.005	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.089	0.21	-10000	0	-0.41	84	84
HRAS	0.02	0.005	-10000	0	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	-0.11	0.18	-10000	0	-0.35	86	86
HIF1A	0.02	0.003	-10000	0	-10000	0	0
FRS2	0.02	0.003	-10000	0	-10000	0	0
oxygen and reactive oxygen species metabolic process	-0.093	0.2	-10000	0	-0.41	83	83
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.006	0.064	-10000	0	-0.29	13	13
Nck/Pak	0.021	0.014	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.11	0.21	-10000	0	-0.43	88	88
mol:GDP	-0.087	0.19	-10000	0	-0.38	85	85
mol:NADP	-0.094	0.19	0.29	5	-0.36	85	90
eNOS/Hsp90	-0.084	0.18	0.34	2	-0.34	85	87
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
mol:IP3	-0.13	0.18	0.17	4	-0.41	84	88
HIF1A/ARNT	0.028	0.009	-10000	0	-10000	0	0
SHB	0.02	0.003	-10000	0	-10000	0	0
VEGFA	0.02	0.005	-10000	0	-10000	0	0
VEGFC	0.01	0.054	-10000	0	-0.29	9	9
FAK1/Vinculin	-0.16	0.25	0.27	3	-0.52	87	90
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.019	0.006	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.11	0.22	-10000	0	-0.44	87	87
PTPN6	0.02	0.005	-10000	0	-10000	0	0
EPAS1	-0.068	0.14	-10000	0	-0.28	86	86
mol:L-citrulline	-0.094	0.19	0.29	5	-0.36	85	90
ITGAV	0.02	0.004	-10000	0	-10000	0	0
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.095	0.21	-10000	0	-0.41	84	84
VEGFR2 homodimer/VEGFA homodimer	-0.11	0.21	-10000	0	-0.44	85	85
VEGFR2/3 heterodimer	-0.16	0.22	-10000	0	-0.48	87	87
VEGFB	0.02	0.003	-10000	0	-10000	0	0
MAPK11	-0.12	0.19	0.22	4	-0.42	82	86
VEGFR2 homodimer	-0.16	0.24	-10000	0	-0.55	80	80
FLT1	0.019	0.019	-10000	0	-0.29	1	1
NEDD4	0.02	0.005	-10000	0	-10000	0	0
MAPK3	-0.12	0.17	0.21	4	-0.38	82	86
MAPK1	-0.12	0.17	0.22	3	-0.38	82	85
VEGFA145/NRP2	0.023	0.032	-10000	0	-0.2	5	5
VEGFR1/2 heterodimer	-0.15	0.21	-10000	0	-0.47	85	85
KDR	-0.16	0.24	-10000	0	-0.55	80	80
VEGFA165/NRP1/VEGFR2 homodimer	-0.1	0.2	-10000	0	-0.41	85	85
SRC	0.019	0.006	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	-0.12	0.18	0.29	6	-0.38	84	90
PI3K	-0.13	0.19	-10000	0	-0.43	78	78
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.1	0.2	-10000	0	-0.4	84	84
FES	-0.13	0.18	0.17	4	-0.42	83	87
GAB1	-0.15	0.22	-10000	0	-0.47	86	86
VEGFR2 homodimer/VEGFA homodimer/Src	-0.11	0.21	-10000	0	-0.43	84	84
CTNNB1	0.019	0.006	-10000	0	-10000	0	0
SOS1	0.02	0.003	-10000	0	-10000	0	0
ARNT	0.019	0.006	-10000	0	-10000	0	0
eNOS/Caveolin-1	-0.089	0.18	0.27	4	-0.35	85	89
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.11	0.21	-10000	0	-0.43	85	85
PI3K/GAB1	-0.1	0.21	-10000	0	-0.44	74	74
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.084	0.19	-10000	0	-0.38	83	83
PRKACA	0.02	0.004	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.12	0.22	-10000	0	-0.44	90	90
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
CDC42	-0.14	0.18	0.17	4	-0.42	83	87
actin cytoskeleton reorganization	-0.1	0.21	0.2	3	-0.42	85	88
PTK2	-0.17	0.26	0.3	2	-0.55	87	89
EDG1	-0.13	0.18	0.16	4	-0.4	85	89
mol:DAG	-0.13	0.18	0.17	4	-0.41	84	88
CaM/Ca2+	-0.12	0.17	0.16	3	-0.38	83	86
MAP2K3	-0.11	0.16	0.16	1	-0.35	81	82
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.1	0.2	-10000	0	-0.43	80	80
PLCG1	-0.13	0.18	0.17	4	-0.41	84	88
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.095	0.21	-10000	0	-0.41	84	84
IQGAP1	0.02	0.004	-10000	0	-10000	0	0
YES1	0.02	0.005	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.11	0.21	-10000	0	-0.44	85	85
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.11	0.21	-10000	0	-0.44	85	85
cell migration	-0.15	0.22	0.28	3	-0.47	87	90
mol:PI-3-4-5-P3	-0.12	0.18	-10000	0	-0.4	78	78
FYN	0.015	0.04	-10000	0	-0.29	5	5
VEGFB/NRP1	-0.13	0.17	0.16	4	-0.39	85	89
mol:NO	-0.094	0.19	0.29	5	-0.36	85	90
PXN	0.021	0.001	-10000	0	-10000	0	0
HRAS/GTP	-0.13	0.15	-10000	0	-0.36	83	83
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.14	0.18	-10000	0	-0.43	80	80
VHL	0.019	0.005	-10000	0	-10000	0	0
ITGB3	-0.016	0.1	-10000	0	-0.29	34	34
NOS3	-0.11	0.21	0.32	4	-0.4	85	89
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.11	0.22	-10000	0	-0.43	90	90
RAC1	0.02	0.003	-10000	0	-10000	0	0
PRKCA	-0.13	0.17	0.16	3	-0.39	82	85
PRKCB	-0.13	0.17	0.16	3	-0.39	83	86
VCL	0.02	0.003	-10000	0	-10000	0	0
VEGFA165/NRP1	-0.13	0.18	0.16	4	-0.4	85	89
VEGFR1/2 heterodimer/VEGFA homodimer	-0.11	0.21	-10000	0	-0.43	86	86
VEGFA165/NRP2	0.023	0.032	-10000	0	-0.2	5	5
MAPKKK cascade	-0.12	0.17	-10000	0	-0.38	78	78
NRP2	0.014	0.041	-10000	0	-0.29	5	5
VEGFC homodimer	0.01	0.054	-10000	0	-0.29	9	9
NCK1	0.015	0.009	-10000	0	-10000	0	0
ROCK1	0.02	0.002	-10000	0	-10000	0	0
FAK1/Paxillin	-0.16	0.25	0.27	3	-0.52	87	90
MAP3K13	-0.11	0.16	0.17	1	-0.36	82	83
PDPK1	-0.11	0.16	-10000	0	-0.37	78	78

×

Plasma membrane estrogen receptor signaling

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
GNB1/GNG2	-0.019	0.091	-10000	0	-0.15	92	92
ER alpha/Gai/GDP/Gbeta gamma	-0.16	0.19	-10000	0	-0.37	105	105
AKT1	-0.25	0.34	-10000	0	-0.67	112	112
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.25	0.34	-10000	0	-0.68	112	112
mol:Ca2+	-0.1	0.15	0.29	1	-0.33	79	80
IGF1R	0.018	0.026	-10000	0	-0.29	2	2
E2/ER alpha (dimer)/Striatin	-0.037	0.09	-10000	0	-0.17	94	94
SHC1	0.019	0.006	-10000	0	-10000	0	0
apoptosis	0.24	0.32	0.64	112	-10000	0	112
RhoA/GTP	-0.063	0.055	-10000	0	-0.15	78	78
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.14	0.19	-10000	0	-0.37	96	96
regulation of stress fiber formation	0.056	0.062	0.23	2	-0.2	3	5
E2/ERA-ERB (dimer)	-0.037	0.09	-10000	0	-0.17	93	93
KRAS	0.019	0.005	-10000	0	-10000	0	0
G13/GTP	-0.032	0.081	-10000	0	-0.15	93	93
pseudopodium formation	-0.056	0.062	0.2	3	-0.23	2	5
E2/ER alpha (dimer)/PELP1	-0.038	0.089	-10000	0	-0.17	95	95
GRB2	0.02	0.005	-10000	0	-10000	0	0
GNG2	0.02	0.003	-10000	0	-10000	0	0
GNAO1	0.016	0.032	-10000	0	-0.29	3	3
HRAS	0.02	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.18	0.22	0.23	1	-0.43	116	117
E2/ER beta (dimer)	0.015	0.002	-10000	0	-10000	0	0
mol:GDP	-0.11	0.13	-10000	0	-0.27	104	104
mol:NADP	-0.18	0.22	0.23	1	-0.43	116	117
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
mol:IP3	-0.11	0.15	-10000	0	-0.34	79	79
IGF-1R heterotetramer	0.018	0.026	-10000	0	-0.29	2	2
PLCB1	-0.11	0.15	-10000	0	-0.35	78	78
PLCB2	-0.11	0.16	-10000	0	-0.35	82	82
IGF1	-0.079	0.14	-10000	0	-0.29	93	93
mol:L-citrulline	-0.18	0.22	0.23	1	-0.43	116	117
RHOA	0.019	0.006	-10000	0	-10000	0	0
Gai/GDP	-0.11	0.23	-10000	0	-0.66	37	37
JNK cascade	0.015	0.002	-10000	0	-10000	0	0
BCAR1	0.02	0.004	-10000	0	-10000	0	0
ESR2	0.02	0.003	-10000	0	-10000	0	0
GNAQ	0.02	0.003	-10000	0	-10000	0	0
ESR1	-0.082	0.14	-10000	0	-0.29	95	95
Gq family/GDP/Gbeta gamma	-0.077	0.19	-10000	0	-0.75	16	16
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.061	0.12	-10000	0	-0.68	3	3
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.14	0.19	-10000	0	-0.37	92	92
GNAZ	-0.05	0.13	-10000	0	-0.29	66	66
E2/ER alpha (dimer)	-0.054	0.098	-10000	0	-0.2	95	95
STRN	0.02	0.003	-10000	0	-10000	0	0
GNAL	0.008	0.059	-10000	0	-0.29	11	11
PELP1	0.019	0.006	-10000	0	-10000	0	0
MAPK11	-0.014	0.004	-10000	0	-10000	0	0
GNAI2	0.019	0.006	-10000	0	-10000	0	0
GNAI3	0.02	0.002	-10000	0	-10000	0	0
GNAI1	0.019	0.019	-10000	0	-0.29	1	1
HBEGF	-0.13	0.2	0.33	11	-0.44	49	60
cAMP biosynthetic process	-0.034	0.078	-10000	0	-0.14	97	97
SRC	-0.14	0.19	0.25	2	-0.36	98	100
PI3K	0.019	0.015	-10000	0	-10000	0	0
GNB1	0.02	0.004	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.067	0.14	-10000	0	-0.26	92	92
SOS1	0.02	0.003	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.15	0.16	-10000	0	-0.34	111	111
Gs family/GTP	-0.031	0.082	-10000	0	-0.14	97	97
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.036	0.012	-10000	0	-10000	0	0
vasodilation	-0.17	0.21	0.22	1	-0.41	116	117
mol:DAG	-0.11	0.15	-10000	0	-0.34	79	79
Gs family/GDP/Gbeta gamma	-0.11	0.11	-10000	0	-0.26	100	100
MSN	-0.059	0.065	0.21	3	-0.24	2	5
Gq family/GTP	-0.1	0.17	-10000	0	-0.36	82	82
mol:PI-3-4-5-P3	-0.24	0.33	-10000	0	-0.65	112	112
NRAS	0.021	0.002	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.17	0.21	0.41	116	-0.22	1	117
GRB2/SOS1	0.028	0.008	-10000	0	-10000	0	0
RhoA/GDP	-0.083	0.14	-10000	0	-0.27	100	100
NOS3	-0.19	0.24	0.23	1	-0.45	116	117
GNA11	0.019	0.019	-10000	0	-0.29	1	1
MAPKKK cascade	-0.19	0.26	0.25	1	-0.51	109	110
E2/ER alpha (dimer)/PELP1/Src	-0.14	0.2	0.24	2	-0.38	100	102
ruffle organization	-0.056	0.062	0.2	3	-0.23	2	5
ROCK2	-0.057	0.07	0.21	4	-0.25	1	5
GNA14	-0.066	0.14	-10000	0	-0.29	81	81
GNA15	0.035	0.064	0.29	17	-10000	0	17
GNA13	0.02	0.003	-10000	0	-10000	0	0
MMP9	-0.12	0.19	0.36	11	-0.45	44	55
MMP2	-0.14	0.19	0.33	4	-0.45	49	53

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.029	0.007	-10000	0	-10000	0	0
Necdin/E2F1	-0.056	0.12	0.22	6	-0.2	107	113
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.048	0.12	-10000	0	-0.18	129	129
NGF (dimer)/p75(NTR)/BEX1	-0.14	0.14	-10000	0	-0.23	190	190
NT-4/5 (dimer)/p75(NTR)	0.11	0.12	0.22	152	-0.2	17	169
IKBKB	0.02	0.005	-10000	0	-10000	0	0
AKT1	-0.025	0.12	0.17	51	-0.28	10	61
IKBKG	0.02	0.004	-10000	0	-10000	0	0
BDNF	0.035	0.063	0.29	16	-10000	0	16
MGDIs/NGR/p75(NTR)/LINGO1	0.023	0.057	-10000	0	-0.17	22	22
FURIN	0.02	0.004	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	0.034	0.063	0.21	13	-0.17	18	31
LINGO1	0.016	0.036	-10000	0	-0.29	4	4
Sortilin/TRAF6/NRIF	-0.034	0.016	-10000	0	-10000	0	0
proBDNF (dimer)	0.035	0.063	0.29	16	-10000	0	16
NTRK1	0.017	0.009	-10000	0	-10000	0	0
RTN4R	0.02	0.003	-10000	0	-10000	0	0
neuron apoptosis	-0.056	0.1	0.32	2	-0.3	18	20
IRAK1	0.02	0.004	-10000	0	-10000	0	0
SHC1	-0.087	0.088	-10000	0	-0.19	116	116
ARHGDIA	0.02	0.004	-10000	0	-10000	0	0
RhoA/GTP	0.014	0.004	-10000	0	-10000	0	0
Gamma Secretase	0.051	0.024	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.051	0.12	-10000	0	-0.18	125	125
MAGEH1	0.008	0.059	-10000	0	-0.29	11	11
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.11	0.14	-10000	0	-0.22	174	174
Mammalian IAPs/DIABLO	0.042	0.024	0.21	1	-10000	0	1
proNGF (dimer)	-0.11	0.15	-10000	0	-0.29	122	122
MAGED1	0.018	0.026	-10000	0	-0.29	2	2
APP	0.02	0.004	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.16	0.14	0.29	153	-10000	0	153
ZNF274	0.02	0.005	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.06	0.093	-10000	0	-0.16	126	126
NGF	-0.11	0.15	-10000	0	-0.29	122	122
cell cycle arrest	-0.046	0.092	0.24	5	-0.24	13	18
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.079	0.11	-10000	0	-0.2	119	119
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.11	0.11	0.21	146	-0.17	17	163
NCSTN	0.019	0.005	-10000	0	-10000	0	0
mol:GTP	-0.059	0.12	-10000	0	-0.19	127	127
PSENEN	0.02	0.005	-10000	0	-10000	0	0
mol:ceramide	-0.082	0.084	0.17	4	-0.18	118	122
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.047	0.088	-10000	0	-0.28	19	19
p75(NTR)/beta APP	0.015	0.056	-10000	0	-0.2	18	18
BEX1	-0.12	0.15	-10000	0	-0.29	126	126
mol:GDP	-0.087	0.088	-10000	0	-0.18	127	127
NGF (dimer)	-0.047	0.1	0.21	2	-0.17	121	123
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.032	0.057	-10000	0	-0.16	22	22
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
RAC1/GTP	-0.048	0.099	-10000	0	-0.16	126	126
MYD88	0.019	0.005	-10000	0	-10000	0	0
CHUK	0.02	0.003	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.059	0.12	-10000	0	-0.19	127	127
RHOB	0.019	0.019	-10000	0	-0.29	1	1
RHOA	0.019	0.006	-10000	0	-10000	0	0
MAGE-G1/E2F1	0.03	0.029	0.22	6	-10000	0	6
NT3 (dimer)	-0.021	0.1	-10000	0	-0.29	36	36
TP53	-0.02	0.059	0.17	17	-10000	0	17
PRDM4	-0.087	0.084	0.17	4	-0.18	125	129
BDNF (dimer)	0.068	0.1	0.23	68	-0.14	17	85
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
SORT1	0.02	0.002	-10000	0	-10000	0	0
activation of caspase activity	-0.05	0.12	-10000	0	-0.18	129	129
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.047	0.11	-10000	0	-0.18	124	124
RHOC	0.021	0.002	-10000	0	-10000	0	0
XIAP	0.021	0.002	-10000	0	-10000	0	0
MAPK10	-0.12	0.13	0.4	2	-0.32	57	59
DIABLO	0.021	0.001	-10000	0	-10000	0	0
SMPD2	-0.083	0.084	0.17	4	-0.18	118	122
APH1B	0.02	0.003	-10000	0	-10000	0	0
APH1A	0.019	0.005	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.059	0.12	-10000	0	-0.19	126	126
PSEN1	0.02	0.003	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.03	0.005	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.014	0.094	-10000	0	-0.22	50	50
MAPK8	-0.084	0.1	0.4	2	-0.27	28	30
MAPK9	-0.083	0.1	0.52	1	-0.27	30	31
APAF1	0.021	0.001	-10000	0	-10000	0	0
NTF3	-0.021	0.1	-10000	0	-0.29	36	36
NTF4	0.16	0.14	0.29	153	-10000	0	153
NDN	-0.1	0.15	-10000	0	-0.29	114	114
RAC1/GDP	0.015	0.002	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.041	0.1	-10000	0	-0.16	120	120
p75 CTF/Sortilin/TRAF6/NRIF	0.047	0.018	-10000	0	-10000	0	0
RhoA-B-C/GTP	-0.059	0.12	-10000	0	-0.19	127	127
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.049	0.062	0.21	13	-0.16	15	28
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.044	0.063	0.21	13	-0.16	16	29
PRKACB	0.021	0.002	-10000	0	-10000	0	0
proBDNF (dimer)/p75 ECD	0.039	0.043	0.22	16	-10000	0	16
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.017	0.018	0.29	1	-10000	0	1
BIRC2	0.016	0.008	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.09	0.12	0.19	3	-0.24	92	95
BAD	-0.11	0.12	0.38	2	-0.29	48	50
RIPK2	0.02	0.004	-10000	0	-10000	0	0
NGFR	0.001	0.075	-10000	0	-0.29	18	18
CYCS	-0.083	0.088	0.24	5	-0.28	14	19
ADAM17	0.02	0.004	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.047	0.11	-10000	0	-0.18	122	122
BCL2L11	-0.11	0.12	0.38	2	-0.29	48	50
BDNF (dimer)/p75(NTR)	0.024	0.069	0.22	13	-0.2	18	31
PI3K	-0.029	0.095	-10000	0	-0.18	77	77
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.047	0.12	-10000	0	-0.18	125	125
NDNL2	0.02	0.004	-10000	0	-10000	0	0
YWHAE	0.019	0.006	-10000	0	-10000	0	0
PRKCI	0.013	0.01	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.079	0.13	-10000	0	-0.22	127	127
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.046	0.12	-10000	0	-0.18	124	124
TRAF6	0.02	0.004	-10000	0	-10000	0	0
RAC1	0.02	0.003	-10000	0	-10000	0	0
PRKCZ	0.02	0.004	-10000	0	-10000	0	0
PLG	-0.007	0.034	0.29	3	-10000	0	3
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.084	0.088	-10000	0	-0.18	119	119
SQSTM1	0.02	0.004	-10000	0	-10000	0	0
NGFRAP1	0.008	0.062	-10000	0	-0.29	12	12
CASP3	-0.1	0.11	0.36	2	-0.27	52	54
E2F1	0.024	0.04	0.29	6	-10000	0	6
CASP9	0.02	0.003	-10000	0	-10000	0	0
IKK complex	-0.055	0.13	-10000	0	-0.25	72	72
NGF (dimer)/TRKA	-0.062	0.11	-10000	0	-0.2	112	112
MMP7	-0.001	0.078	0.29	2	-0.29	18	20
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.037	0.11	-10000	0	-0.17	117	117
MMP3	0.08	0.12	0.29	68	-10000	0	68
APAF-1/Caspase 9	-0.086	0.067	-10000	0	-0.25	13	13

×

PLK1 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
regulation of centriole-centriole cohesion	-0.076	0.056	0.12	18	-0.096	247	265
BUB1B	0.088	0.046	0.12	116	-0.12	2	118
PLK1	0.025	0.03	0.09	28	-0.077	1	29
PLK1S1	0.016	0.031	0.11	8	-0.16	4	12
KIF2A	0.015	0.026	0.11	5	-10000	0	5
regulation of mitotic centrosome separation	0.025	0.03	0.09	27	-0.077	1	28
GOLGA2	0.021	0.002	-10000	0	-10000	0	0
Hec1/SPC24	0.054	0.056	0.22	24	-10000	0	24
WEE1	0.011	0.069	-10000	0	-0.31	11	11
cytokinesis	0.11	0.056	0.17	37	-0.16	1	38
PP2A-alpha B56	0.11	0.11	-10000	0	-0.5	5	5
AURKA	0.024	0.035	0.13	21	-0.17	1	22
PICH/PLK1	0.03	0.064	0.17	42	-10000	0	42
CENPE	0.015	0.027	0.098	11	-10000	0	11
RhoA/GTP	0.014	0.004	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.016	0.026	0.11	5	-10000	0	5
PPP2CA	0.02	0.005	-10000	0	-10000	0	0
FZR1	0.019	0.005	-10000	0	-10000	0	0
TPX2	0.11	0.023	0.11	280	-10000	0	280
PAK1	0.018	0.006	-10000	0	-10000	0	0
SPC24	0.043	0.077	0.29	25	-10000	0	25
FBXW11	0.02	0.004	-10000	0	-10000	0	0
CLSPN	0.11	0.039	0.14	117	-10000	0	117
GORASP1	0.019	0.005	-10000	0	-10000	0	0
metaphase	0	0.002	0.011	1	-0.011	2	3
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.012	0.016	0.05	21	-0.041	1	22
G2 phase of mitotic cell cycle	-0.001	0.002	0.012	1	-10000	0	1
STAG2	0.021	0.002	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	-0.025	0.13	-10000	0	-0.49	22	22
spindle elongation	0.025	0.03	0.09	27	-0.077	1	28
ODF2	0.02	0.006	-10000	0	-10000	0	0
BUB1	0.11	0.12	-10000	0	-0.57	5	5
TPT1	0.006	0.047	-10000	0	-0.17	17	17
CDC25C	0.11	0.079	0.15	176	-0.22	11	187
CDC25B	0.019	0.009	-10000	0	-10000	0	0
SGOL1	0.076	0.056	0.096	247	-0.12	18	265
RHOA	0.019	0.006	-10000	0	-10000	0	0
CCNB1/CDK1	0.03	0.025	-10000	0	-10000	0	0
CDC14B	-0.01	0.003	-10000	0	-10000	0	0
CDC20	0.29	0.041	0.29	286	-10000	0	286
PLK1/PBIP1	0.039	0.05	0.1	106	-10000	0	106
mitosis	-0.002	0.004	0.017	2	-0.015	9	11
FBXO5	0.01	0.026	0.095	4	-0.1	1	5
CDC2	0.001	0.002	-10000	0	-0.009	1	1
NDC80	0.02	0.004	-10000	0	-10000	0	0
metaphase plate congression	0.018	0.037	-10000	0	-0.22	5	5
ERCC6L	0.026	0.06	0.15	40	-10000	0	40
NLP/gamma Tubulin	0.014	0.018	0.073	10	-10000	0	10
microtubule cytoskeleton organization	0.006	0.047	-10000	0	-0.17	17	17
G2/M transition DNA damage checkpoint	-0.001	0.003	0.013	10	-10000	0	10
PPP1R12A	0.021	0.003	-10000	0	-10000	0	0
interphase	-0.001	0.003	0.013	10	-10000	0	10
PLK1/PRC1-2	0.19	0.064	0.21	264	-10000	0	264
GRASP65/GM130/RAB1/GTP/PLK1	0.044	0.028	-10000	0	-10000	0	0
RAB1A	0.02	0.003	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.018	0.026	0.083	28	-10000	0	28
mitotic prometaphase	0.001	0.003	0.017	6	-10000	0	6
proteasomal ubiquitin-dependent protein catabolic process	0.057	0.057	0.18	4	-0.34	2	6
microtubule-based process	0.2	0.054	0.21	275	-10000	0	275
Golgi organization	0.025	0.03	0.09	27	-0.077	1	28
Cohesin/SA2	0.032	0.024	0.11	6	-10000	0	6
PPP1CB/MYPT1	0.03	0.007	-10000	0	-10000	0	0
KIF20A	0.28	0.068	0.29	275	-10000	0	275
APC/C/CDC20	0.21	0.038	0.21	286	-10000	0	286
PPP2R1A	0.02	0.004	-10000	0	-10000	0	0
chromosome segregation	0.038	0.049	0.1	106	-10000	0	106
PRC1	0.02	0.004	-10000	0	-10000	0	0
ECT2	0.093	0.11	0.23	108	-10000	0	108
C13orf34	0.019	0.025	0.077	27	-10000	0	27
NUDC	0.018	0.037	-10000	0	-0.22	5	5
regulation of attachment of spindle microtubules to kinetochore	0.088	0.046	0.12	119	-0.12	2	121
spindle assembly	0.018	0.025	0.086	17	-0.067	1	18
spindle stabilization	0.016	0.031	0.11	8	-0.16	4	12
APC/C/HCDH1	0.008	0.014	-10000	0	-10000	0	0
MKLP2/PLK1	0.2	0.054	0.21	275	-10000	0	275
CCNB1	0.02	0.007	-10000	0	-10000	0	0
PPP1CB	0.02	0.005	-10000	0	-10000	0	0
BTRC	0.02	0.004	-10000	0	-10000	0	0
ROCK2	0.015	0.051	0.17	1	-0.37	2	3
TUBG1	0.016	0.019	0.1	2	-0.15	1	3
G2/M transition of mitotic cell cycle	0.004	0.022	-10000	0	-10000	0	0
MLF1IP	0.049	0.075	0.14	109	-10000	0	109
INCENP	0.021	0.005	-10000	0	-10000	0	0

×

TCGA08_retinoblastoma

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
CDKN2B	0.022	0.03	0.3	2	-10000	0	2
CDKN2C	-0.031	0.019	-10000	0	-10000	0	0
CDKN2A	0.27	0.083	0.3	265	-10000	0	265
CCND2	-0.074	0.048	-10000	0	-0.18	25	25
RB1	0.079	0.048	0.21	19	-10000	0	19
CDK4	-0.082	0.048	-10000	0	-0.21	19	19
CDK6	-0.083	0.051	-10000	0	-0.19	28	28
G1/S progression	-0.078	0.052	0.18	2	-0.2	20	22

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.19	0.25	0.35	6	-0.56	60	66
HDAC7	0.021	0.003	-10000	0	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.18	0.28	0.47	5	-0.63	51	56
SMAD4	0.019	0.005	-10000	0	-10000	0	0
ID2	-0.18	0.26	0.39	4	-0.57	55	59
AP1	0.011	0.062	-10000	0	-0.2	22	22
ABCG2	-0.24	0.29	0.39	4	-0.6	86	90
HIF1A	-0.044	0.064	0.16	1	-0.19	6	7
TFF3	-0.19	0.3	0.44	9	-0.6	69	78
GATA2	0.009	0.048	-10000	0	-0.29	7	7
AKT1	-0.054	0.079	-10000	0	-0.21	29	29
response to hypoxia	-0.051	0.067	0.13	1	-0.18	33	34
MCL1	-0.18	0.26	0.4	3	-0.57	58	61
NDRG1	-0.17	0.25	0.39	4	-0.57	52	56
SERPINE1	-0.18	0.26	0.39	4	-0.56	57	61
FECH	-0.18	0.26	0.39	4	-0.57	58	62
FURIN	-0.18	0.26	0.39	4	-0.57	57	61
NCOA2	0.012	0.039	-10000	0	-0.29	4	4
EP300	-0.062	0.11	0.19	1	-0.32	36	37
HMOX1	-0.18	0.26	0.39	4	-0.57	58	62
BHLHE40	-0.18	0.26	0.4	3	-0.57	58	61
BHLHE41	-0.18	0.26	0.39	4	-0.57	56	60
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.042	0.1	0.27	1	-0.32	2	3
ENG	-0.05	0.094	0.25	2	-0.3	2	4
JUN	0.019	0.019	-10000	0	-0.29	1	1
RORA	-0.18	0.26	0.39	4	-0.57	57	61
ABCB1	-0.28	0.4	-10000	0	-0.86	90	90
TFRC	-0.15	0.23	0.4	3	-0.57	40	43
CXCR4	-0.18	0.26	0.39	4	-0.57	58	62
TF	-0.16	0.25	0.42	6	-0.56	49	55
CITED2	-0.19	0.27	0.39	4	-0.57	65	69
HIF1A/ARNT	-0.18	0.31	0.65	5	-0.65	45	50
LDHA	-0.078	0.19	-10000	0	-0.66	24	24
ETS1	-0.18	0.26	0.4	3	-0.57	57	60
PGK1	-0.18	0.26	0.39	4	-0.56	60	64
NOS2	-0.18	0.27	0.44	6	-0.57	60	66
ITGB2	-0.18	0.26	0.39	4	-0.57	58	62
ALDOA	-0.18	0.26	0.39	4	-0.57	58	62
Cbp/p300/CITED2	-0.23	0.32	0.48	1	-0.71	60	61
FOS	-0.003	0.082	-10000	0	-0.29	22	22
HK2	-0.15	0.28	0.46	8	-0.56	56	64
SP1	-0.017	0.061	-10000	0	-0.12	41	41
GCK	-0.16	0.36	-10000	0	-1.2	31	31
HK1	-0.18	0.26	0.39	4	-0.57	58	62
NPM1	-0.18	0.26	0.39	4	-0.56	59	63
EGLN1	-0.18	0.26	0.4	3	-0.57	56	59
CREB1	0.02	0.006	-10000	0	-10000	0	0
PGM1	-0.18	0.26	0.39	4	-0.57	57	61
SMAD3	0.02	0.003	-10000	0	-10000	0	0
EDN1	-0.068	0.17	0.37	1	-0.48	26	27
IGFBP1	-0.19	0.27	0.39	4	-0.58	61	65
VEGFA	-0.16	0.25	0.38	1	-0.56	53	54
HIF1A/JAB1	-0.024	0.054	-10000	0	-0.15	1	1
CP	-0.15	0.26	0.43	9	-0.59	46	55
CXCL12	-0.25	0.3	0.39	4	-0.59	97	101
COPS5	0.016	0.015	-10000	0	-10000	0	0
SMAD3/SMAD4	0.028	0.009	-10000	0	-10000	0	0
BNIP3	-0.18	0.26	0.39	4	-0.57	59	63
EGLN3	-0.18	0.26	0.4	3	-0.57	58	61
CA9	-0.13	0.29	0.46	10	-0.55	55	65
TERT	-0.17	0.24	0.39	3	-0.57	47	50
ENO1	-0.18	0.26	0.39	4	-0.57	58	62
PFKL	-0.18	0.26	0.39	4	-0.57	58	62
NCOA1	0.018	0.011	-10000	0	-10000	0	0
ADM	-0.18	0.26	0.4	3	-0.57	58	61
ARNT	-0.038	0.062	-10000	0	-0.21	2	2
HNF4A	0.008	0.06	0.3	5	-0.2	6	11
ADFP	-0.19	0.25	0.35	6	-0.56	60	66
SLC2A1	-0.16	0.25	0.38	2	-0.56	53	55
LEP	-0.17	0.27	0.44	4	-0.57	57	61
HIF1A/ARNT/Cbp/p300	-0.19	0.29	0.48	5	-0.64	55	60
EPO	-0.17	0.27	0.39	1	-0.72	37	38
CREBBP	-0.06	0.11	0.19	1	-0.32	35	36
HIF1A/ARNT/Cbp/p300/HDAC7	-0.17	0.29	0.47	5	-0.65	47	52
PFKFB3	-0.18	0.26	0.39	4	-0.57	58	62
NT5E	-0.2	0.28	0.39	4	-0.58	74	78

×

Endothelins

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
AKT1	-0.079	0.097	-10000	0	-0.34	22	22
PTK2B	0.019	0.006	-10000	0	-10000	0	0
mol:Ca2+	-0.1	0.19	-10000	0	-0.61	19	19
EDN1	-0.023	0.061	-10000	0	-0.2	5	5
EDN3	-0.077	0.13	0.29	1	-0.29	75	76
EDN2	0.19	0.13	0.29	182	-10000	0	182
HRAS/GDP	-0.13	0.17	0.26	1	-0.39	62	63
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.096	0.14	-10000	0	-0.31	70	70
ADCY4	-0.074	0.1	0.19	1	-0.28	37	38
ADCY5	-0.086	0.12	0.18	4	-0.27	65	69
ADCY6	-0.065	0.091	0.19	1	-0.27	27	28
ADCY7	-0.066	0.09	0.18	2	-0.27	27	29
ADCY1	-0.069	0.096	0.17	7	-0.28	30	37
ADCY2	-0.092	0.11	0.17	1	-0.26	68	69
ADCY3	-0.065	0.091	0.19	1	-0.28	26	27
ADCY8	-0.062	0.088	0.17	5	-0.28	23	28
ADCY9	-0.065	0.089	0.19	1	-0.28	26	27
arachidonic acid secretion	-0.13	0.17	-10000	0	-0.4	63	63
ETB receptor/Endothelin-1/Gq/GTP	-0.099	0.15	-10000	0	-0.28	100	100
GNAO1	0.016	0.032	-10000	0	-0.29	3	3
HRAS	0.018	0.009	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	-0.042	0.11	-10000	0	-0.31	20	20
ETA receptor/Endothelin-1/Gs/GTP	-0.044	0.11	-10000	0	-0.28	28	28
mol:GTP	-0.001	0.002	-10000	0	-10000	0	0
COL3A1	-0.085	0.12	-10000	0	-0.43	21	21
EDNRB	-0.052	0.13	-10000	0	-0.29	63	63
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.077	0.097	0.27	1	-0.34	21	22
CYSLTR1	-0.08	0.096	-10000	0	-0.34	20	20
SLC9A1	-0.043	0.073	-10000	0	-0.22	22	22
mol:GDP	-0.14	0.17	0.23	3	-0.41	62	65
SLC9A3	-0.13	0.26	-10000	0	-0.58	59	59
RAF1	-0.14	0.17	0.23	1	-0.39	72	73
JUN	-0.12	0.19	-10000	0	-0.59	23	23
JAK2	-0.079	0.097	-10000	0	-0.34	22	22
mol:IP3	-0.12	0.16	-10000	0	-0.37	68	68
ETA receptor/Endothelin-1	-0.064	0.13	-10000	0	-0.35	28	28
PLCB1	0.013	0.033	-10000	0	-0.29	3	3
PLCB2	0.016	0.013	-10000	0	-10000	0	0
ETA receptor/Endothelin-3	-0.087	0.13	0.22	1	-0.24	104	105
FOS	-0.15	0.23	-10000	0	-0.71	32	32
Gai/GDP	-0.11	0.25	-10000	0	-0.72	37	37
CRK	0.019	0.006	-10000	0	-10000	0	0
mol:Ca ++	-0.14	0.17	-10000	0	-0.39	74	74
BCAR1	0.02	0.004	-10000	0	-10000	0	0
PRKCB1	-0.12	0.15	-10000	0	-0.35	70	70
GNAQ	0.016	0.013	-10000	0	-10000	0	0
GNAZ	-0.05	0.13	-10000	0	-0.29	66	66
GNAL	0.008	0.059	-10000	0	-0.29	11	11
Gs family/GDP	-0.13	0.16	0.25	1	-0.38	63	64
ETA receptor/Endothelin-1/Gq/GTP	-0.1	0.14	-10000	0	-0.31	71	71
MAPK14	-0.097	0.14	-10000	0	-0.33	62	62
TRPC6	-0.11	0.2	-10000	0	-0.67	17	17
GNAI2	0.019	0.006	-10000	0	-10000	0	0
GNAI3	0.02	0.002	-10000	0	-10000	0	0
GNAI1	0.019	0.019	-10000	0	-0.29	1	1
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.097	0.15	0.17	1	-0.34	66	67
ETB receptor/Endothelin-2	0.073	0.15	0.21	132	-0.16	61	193
ETB receptor/Endothelin-3	-0.076	0.12	0.22	1	-0.22	119	120
ETB receptor/Endothelin-1	-0.053	0.1	-10000	0	-0.23	66	66
MAPK3	-0.16	0.22	-10000	0	-0.58	46	46
MAPK1	-0.16	0.23	-10000	0	-0.59	45	45
Rac1/GDP	-0.12	0.17	0.24	2	-0.39	62	64
cAMP biosynthetic process	-0.13	0.14	0.29	4	-0.3	79	83
MAPK8	-0.13	0.22	-10000	0	-0.59	39	39
SRC	0.019	0.006	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.093	0.12	-10000	0	-0.3	49	49
p130Cas/CRK/Src/PYK2	-0.12	0.18	0.26	2	-0.42	54	56
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.12	0.17	0.24	2	-0.39	61	63
COL1A2	-0.11	0.18	-10000	0	-0.47	41	41
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	0.072	0.15	0.2	130	-0.2	42	172
mol:DAG	-0.12	0.16	-10000	0	-0.37	68	68
MAP2K2	-0.15	0.19	-10000	0	-0.44	67	67
MAP2K1	-0.15	0.19	-10000	0	-0.44	67	67
EDNRA	-0.063	0.13	-10000	0	-0.34	43	43
positive regulation of muscle contraction	-0.07	0.083	0.18	1	-0.29	21	22
Gq family/GDP	-0.11	0.17	0.28	1	-0.37	67	68
HRAS/GTP	-0.13	0.17	0.24	2	-0.38	71	73
PRKCH	-0.12	0.15	0.19	1	-0.36	69	70
RAC1	0.02	0.003	-10000	0	-10000	0	0
PRKCA	-0.12	0.16	0.19	1	-0.36	67	68
PRKCB	-0.12	0.16	-10000	0	-0.36	68	68
PRKCE	-0.11	0.15	-10000	0	-0.36	64	64
PRKCD	-0.11	0.15	-10000	0	-0.36	66	66
PRKCG	-0.11	0.15	-10000	0	-0.36	62	62
regulation of vascular smooth muscle contraction	-0.18	0.28	-10000	0	-0.84	32	32
PRKCQ	-0.12	0.15	-10000	0	-0.36	68	68
PLA2G4A	-0.14	0.18	-10000	0	-0.43	63	63
GNA14	-0.069	0.14	-10000	0	-0.29	81	81
GNA15	0.032	0.066	0.29	17	-10000	0	17
GNA12	0.02	0.003	-10000	0	-10000	0	0
GNA11	0.015	0.022	-10000	0	-0.29	1	1
Rac1/GTP	-0.043	0.11	-10000	0	-0.31	21	21
MMP1	0.1	0.17	0.34	85	-10000	0	85

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.02	0.002	-10000	0	-10000	0	0
PTK2	0.019	0.006	-10000	0	-10000	0	0
CRKL	-0.059	0.073	-10000	0	-0.17	84	84
GRB2/SOS1/SHC	0.036	0.015	-10000	0	-10000	0	0
HRAS	0.02	0.005	-10000	0	-10000	0	0
IRS1/Crk	-0.062	0.071	-10000	0	-0.16	88	88
IGF-1R heterotetramer/IGF1/PTP1B	-0.02	0.096	-10000	0	-0.17	82	82
AKT1	-0.005	0.1	0.15	65	-0.16	46	111
BAD	-0.009	0.098	0.14	63	-0.16	45	108
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.056	0.073	-10000	0	-0.17	80	80
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.04	0.087	-10000	0	-0.17	88	88
RAF1	-0.014	0.14	0.26	4	-0.44	16	20
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.018	0.095	-10000	0	-0.16	81	81
YWHAZ	0.02	0.005	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.039	0.094	-10000	0	-0.17	94	94
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
RPS6KB1	-0.004	0.11	0.15	67	-0.16	47	114
GNB2L1	0.02	0.004	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	0	0.13	0.29	12	-0.33	16	28
PXN	0.021	0.001	-10000	0	-10000	0	0
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.028	0.008	-10000	0	-10000	0	0
HRAS/GTP	-0.059	0.063	-10000	0	-0.16	66	66
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.002	0.09	-10000	0	-0.15	76	76
IGF-1R heterotetramer	-0.006	0.046	-10000	0	-0.16	4	4
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.029	0.095	-10000	0	-0.17	88	88
Crk/p130 Cas/Paxillin	-0.023	0.093	-10000	0	-0.16	87	87
IGF1R	-0.006	0.046	-10000	0	-0.16	4	4
IGF1	0.009	0.045	-10000	0	-0.34	4	4
IRS2/Crk	-0.063	0.074	-10000	0	-0.17	88	88
PI3K	-0.016	0.08	-10000	0	-0.16	61	61
apoptosis	0.002	0.098	0.26	2	-0.21	10	12
HRAS/GDP	0.015	0.003	-10000	0	-10000	0	0
PRKCD	-0.084	0.13	-10000	0	-0.27	87	87
RAF1/14-3-3 E	-0.01	0.13	0.26	4	-0.37	18	22
BAD/14-3-3	-0.003	0.1	0.21	10	-0.27	2	12
PRKCZ	-0.004	0.1	0.15	69	-0.16	47	116
Crk/p130 Cas/Paxillin/FAK1	-0.027	0.084	-10000	0	-0.28	2	2
PTPN1	0.019	0.005	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.085	0.14	-10000	0	-0.28	89	89
BCAR1	0.02	0.004	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.009	0.093	-10000	0	-0.16	80	80
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.02	0.003	-10000	0	-10000	0	0
IRS1/NCK2	-0.04	0.087	-10000	0	-0.17	88	88
GRB10	0.019	0.018	-10000	0	-0.29	1	1
PTPN11	-0.061	0.073	-10000	0	-0.17	88	88
IRS1	-0.055	0.077	0.12	2	-0.18	77	79
IRS2	-0.062	0.077	-10000	0	-0.17	88	88
IGF-1R heterotetramer/IGF1	-0.045	0.12	-10000	0	-0.23	88	88
GRB2	0.02	0.005	-10000	0	-10000	0	0
PDPK1	-0.006	0.11	0.16	64	-0.16	48	112
YWHAE	0.019	0.006	-10000	0	-10000	0	0
PRKD1	-0.1	0.15	-10000	0	-0.3	91	91
SHC1	0.019	0.006	-10000	0	-10000	0	0

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	-0.041	0.11	-10000	0	-0.2	87	87
alphaV beta3 Integrin	-0.043	0.12	-10000	0	-0.2	100	100
PTK2	-0.14	0.19	0.31	3	-0.42	73	76
IGF1R	0.018	0.026	-10000	0	-0.29	2	2
PI4KB	0.019	0.006	-10000	0	-10000	0	0
MFGE8	0.019	0.019	-10000	0	-0.29	1	1
SRC	0.019	0.006	-10000	0	-10000	0	0
CDKN1B	-0.062	0.14	0.16	4	-0.43	33	37
VEGFA	0.02	0.004	-10000	0	-10000	0	0
ILK	-0.062	0.14	-10000	0	-0.42	32	32
ROCK1	0.02	0.002	-10000	0	-10000	0	0
AKT1	-0.071	0.13	-10000	0	-0.38	37	37
PTK2B	-0.065	0.093	0.2	9	-0.27	24	33
alphaV/beta3 Integrin/JAM-A	-0.046	0.12	0.2	4	-0.19	104	108
CBL	0.017	0.008	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.015	0.068	-10000	0	-0.17	33	33
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.022	0.1	-10000	0	-0.17	94	94
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.086	0.14	-10000	0	-0.35	44	44
alphaV/beta3 Integrin/Syndecan-1	0.14	0.11	0.21	216	-0.12	28	244
PI4KA	0.02	0.003	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.083	0.14	-10000	0	-0.22	133	133
PI4 Kinase	0.027	0.01	-10000	0	-10000	0	0
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	0.02	0.075	0.21	9	-0.17	33	42
RPS6KB1	-0.12	0.11	-10000	0	-0.29	60	60
TLN1	0.02	0.003	-10000	0	-10000	0	0
MAPK3	-0.18	0.22	-10000	0	-0.45	105	105
GPR124	-0.044	0.12	-10000	0	-0.29	60	60
MAPK1	-0.18	0.22	-10000	0	-0.45	105	105
PXN	0.021	0.001	-10000	0	-10000	0	0
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	0.016	0.07	0.21	4	-0.17	33	37
cell adhesion	0.007	0.062	-10000	0	-0.19	25	25
ANGPTL3	0.008	0.018	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src	-0.024	0.094	-10000	0	-0.17	82	82
IGF-1R heterotetramer	0.018	0.026	-10000	0	-0.29	2	2
Rac1/GDP	0.015	0.002	-10000	0	-10000	0	0
TGFBR2	0.017	0.026	-10000	0	-0.29	2	2
ITGB3	-0.016	0.1	-10000	0	-0.29	34	34
IGF1	-0.079	0.14	-10000	0	-0.29	93	93
RAC1	0.02	0.003	-10000	0	-10000	0	0
regulation of cell-matrix adhesion	-0.023	0.11	-10000	0	-0.2	74	74
apoptosis	0.02	0.004	-10000	0	-10000	0	0
CD47	0.017	0.008	-10000	0	-10000	0	0
alphaV/beta3 Integrin/CD47	0.016	0.06	-10000	0	-0.17	25	25
VCL	0.02	0.003	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.02	0.11	-10000	0	-0.21	68	68
CSF1	0.018	0.026	-10000	0	-0.29	2	2
PIK3C2A	-0.062	0.14	0.16	4	-0.42	32	36
PI4 Kinase/Pyk2	-0.12	0.11	0.099	2	-0.3	63	65
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.03	0.12	-10000	0	-0.19	93	93
FAK1/Vinculin	-0.11	0.16	0.33	4	-0.34	70	74
alphaV beta3/Integrin/ppsTEM5	-0.023	0.11	-10000	0	-0.2	74	74
RHOA	0.019	0.006	-10000	0	-10000	0	0
VTN	-0.008	0.1	0.29	5	-0.29	29	34
BCAR1	0.02	0.004	-10000	0	-10000	0	0
FGF2	-0.074	0.14	-10000	0	-0.29	88	88
F11R	-0.067	0.084	-10000	0	-0.2	80	80
alphaV/beta3 Integrin/Lactadherin	0.015	0.069	-10000	0	-0.18	32	32
alphaV/beta3 Integrin/TGFBR2	0.013	0.069	-10000	0	-0.17	34	34
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.041	0.027	-10000	0	-0.16	2	2
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	0.017	0.06	-10000	0	-0.15	32	32
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.01	0.051	-10000	0	-0.29	8	8
alphaV/beta3 Integrin/Pyk2	-0.039	0.1	0.16	4	-0.19	79	83
SDC1	0.26	0.09	0.29	258	-10000	0	258
VAV3	-0.023	0.028	0.16	5	-10000	0	5
PTPN11	0.021	0.001	-10000	0	-10000	0	0
IRS1	0.008	0.056	-10000	0	-0.29	10	10
FAK1/Paxillin	-0.11	0.16	0.33	4	-0.34	70	74
cell migration	-0.1	0.14	0.32	4	-0.31	70	74
ITGAV	0.02	0.004	-10000	0	-10000	0	0
PI3K	-0.028	0.096	-10000	0	-0.18	68	68
SPP1	0.03	0.05	0.29	10	-10000	0	10
KDR	-0.073	0.14	-10000	0	-0.29	87	87
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.02	0.004	-10000	0	-10000	0	0
COL4A3	0.02	0.034	0.29	4	-10000	0	4
angiogenesis	-0.18	0.23	-10000	0	-0.46	106	106
Rac1/GTP	-0.025	0.028	0.16	5	-10000	0	5
EDIL3	-0.039	0.12	-10000	0	-0.29	54	54
cell proliferation	0.012	0.069	-10000	0	-0.17	34	34

×

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.081	0.1	0.28	5	-0.27	6	11
KLHL20	0.041	0.052	0.16	11	-10000	0	11
CYFIP2	0.02	0.004	-10000	0	-10000	0	0
Rac1/GDP	0.066	0.08	0.23	24	-10000	0	24
ENAH	0.083	0.12	0.29	13	-0.28	9	22
AP1M1	0.02	0.003	-10000	0	-10000	0	0
RAP1B	0.02	0.003	-10000	0	-10000	0	0
RAP1A	0.021	0.002	-10000	0	-10000	0	0
CTNNB1	0.019	0.006	-10000	0	-10000	0	0
CDC42/GTP	0.022	0.037	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.006	0.016	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.16	0.088	0.21	208	-10000	0	208
RAPGEF1	0.066	0.11	0.26	22	-0.26	10	32
CTNND1	0.02	0.002	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.097	0.12	0.26	1	-0.28	10	11
CRK	0.07	0.11	0.28	19	-0.27	10	29
E-cadherin/gamma catenin/alpha catenin	0.17	0.075	0.21	233	-10000	0	233
alphaE/beta7 Integrin	0.028	0.009	-10000	0	-10000	0	0
IQGAP1	0.02	0.004	-10000	0	-10000	0	0
NCKAP1	0.02	0.004	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.036	0.012	-10000	0	-10000	0	0
DLG1	0.12	0.14	0.29	77	-0.28	7	84
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0.016	-10000	0	-10000	0	0
MLLT4	0.019	0.005	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.036	0.019	-10000	0	-0.16	2	2
PI3K	0.004	0.023	-10000	0	-10000	0	0
ARF6	0.02	0.003	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
E-cadherin/gamma catenin	0.18	0.071	0.22	246	-10000	0	246
TIAM1	0.018	0.026	-10000	0	-0.29	2	2
E-cadherin(dimer)/Ca2+	0.15	0.078	0.2	218	-10000	0	218
AKT1	0.007	0.026	0.099	15	-10000	0	15
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
CDH1	0.26	0.097	0.29	251	-10000	0	251
RhoA/GDP	0.072	0.071	0.24	23	-10000	0	23
actin cytoskeleton organization	0.036	0.044	0.14	14	-10000	0	14
CDC42/GDP	0.065	0.08	0.24	23	-10000	0	23
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.076	0.036	0.14	2	-10000	0	2
ITGB7	0.02	0.003	-10000	0	-10000	0	0
RAC1	0.02	0.003	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.16	0.083	0.21	218	-10000	0	218
E-cadherin/Ca2+/beta catenin/alpha catenin	0.14	0.073	0.18	219	-10000	0	219
mol:GDP	0.062	0.083	0.24	24	-10000	0	24
CDC42/GTP/IQGAP1	0.026	0.007	-10000	0	-10000	0	0
JUP	0.02	0.003	-10000	0	-10000	0	0
p120 catenin/RhoA/GDP	0.073	0.079	0.24	22	-10000	0	22
RAC1/GTP/IQGAP1	0.027	0.006	-10000	0	-10000	0	0
PIP5K1C/AP1M1	0.029	0.008	-10000	0	-10000	0	0
RHOA	0.019	0.006	-10000	0	-10000	0	0
CDC42	0.02	0.003	-10000	0	-10000	0	0
CTNNA1	0.02	0.004	-10000	0	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.03	0.036	0.16	7	-10000	0	7
NME1	0.02	0.002	-10000	0	-10000	0	0
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	0.075	0.11	0.27	2	-0.28	10	12
regulation of cell-cell adhesion	0.014	0.029	-10000	0	-10000	0	0
WASF2	0.015	0.023	-10000	0	-10000	0	0
Rap1/GTP	0.042	0.057	0.19	19	-10000	0	19
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.16	0.085	0.21	210	-10000	0	210
CCND1	0.033	0.037	0.16	5	-10000	0	5
VAV2	0.097	0.12	0.31	11	-10000	0	11
RAP1/GDP	0.057	0.066	0.22	21	-10000	0	21
adherens junction assembly	0.075	0.11	0.27	2	-0.27	10	12
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.02	0.004	-10000	0	-10000	0	0
PIP5K1C	0.019	0.005	-10000	0	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.14	0.082	0.19	201	-10000	0	201
E-cadherin/beta catenin	0.11	0.049	0.13	217	-10000	0	217
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	0.085	0.12	0.29	18	-0.28	10	28
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
Rac1/GTP	-0.008	0.03	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin	0.16	0.083	0.21	219	-10000	0	219
ITGAE	0.019	0.006	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.096	0.12	-10000	0	-0.29	10	10

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	-0.092	0.07	-10000	0	-0.36	6	6
SMARCC2	0.021	0.002	-10000	0	-10000	0	0
SMARCC1	0.019	0.006	-10000	0	-10000	0	0
TBX21	0.11	0.086	0.58	2	-0.63	1	3
SUMO2	0.018	0.009	-10000	0	-10000	0	0
STAT1 (dimer)	0.021	0.004	-10000	0	-10000	0	0
FKBP4	0.02	0.004	-10000	0	-10000	0	0
FKBP5	0.019	0.018	-10000	0	-0.29	1	1
GR alpha/HSP90/FKBP51/HSP90	-0.096	0.065	-10000	0	-0.18	16	16
PRL	-0.17	0.47	0.38	10	-1	65	75
cortisol/GR alpha (dimer)/TIF2	-0.24	0.15	-10000	0	-0.4	101	101
RELA	0.018	0.088	-10000	0	-0.18	32	32
FGG	-0.24	0.15	-10000	0	-0.39	109	109
GR beta/TIF2	-0.11	0.074	-10000	0	-0.2	47	47
IFNG	0.27	0.16	0.46	88	-10000	0	88
apoptosis	-0.092	0.13	-10000	0	-0.5	10	10
CREB1	0.023	0.022	-10000	0	-10000	0	0
histone acetylation	0.005	0.069	0.24	4	-10000	0	4
BGLAP	0.11	0.077	0.32	8	-10000	0	8
GR/PKAc	-0.088	0.065	-10000	0	-0.18	8	8
NF kappa B1 p50/RelA	0.044	0.16	0.28	7	-0.28	43	50
SMARCD1	0.021	0.003	-10000	0	-10000	0	0
MDM2	-0.07	0.044	-10000	0	-0.12	44	44
GATA3	0.047	0.08	0.3	27	-10000	0	27
AKT1	0.019	0.004	-10000	0	-10000	0	0
CSF2	0.02	0.048	-10000	0	-10000	0	0
GSK3B	0.015	0.011	-10000	0	-10000	0	0
NR1I3	-0.073	0.12	-10000	0	-0.49	6	6
CSN2	-0.22	0.14	-10000	0	-0.33	147	147
BRG1/BAF155/BAF170/BAF60A	0.048	0.018	-10000	0	-10000	0	0
NFATC1	0.019	0.019	-10000	0	-0.29	1	1
POU2F1	-0.051	0.13	-10000	0	-0.29	65	65
CDKN1A	-0.001	0.057	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0	0.002	-10000	0	-10000	0	0
SFN	0.28	0.067	0.29	274	-10000	0	274
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.076	0.1	0.26	3	-10000	0	3
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.091	0.15	-10000	0	-0.73	9	9
JUN	0.24	0.13	0.32	174	-0.28	1	175
IL4	0.1	0.068	0.33	1	-10000	0	1
CDK5R1	0.019	0.008	-10000	0	-10000	0	0
PRKACA	0.02	0.004	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.043	0.057	-10000	0	-0.22	9	9
GR alpha/HSP90/FKBP51/HSP90/PP5C	-0.087	0.065	-10000	0	-0.18	3	3
cortisol/GR alpha (monomer)	-0.28	0.18	-10000	0	-0.45	114	114
NCOA2	0.015	0.036	-10000	0	-0.29	4	4
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	0.14	0.083	0.23	92	-0.29	2	94
AP-1/NFAT1-c-4	0.32	0.18	0.42	206	-10000	0	206
AFP	0.17	0.092	0.39	8	-10000	0	8
SUV420H1	0.02	0.004	-10000	0	-10000	0	0
IRF1	-0.14	0.11	-10000	0	-0.46	12	12
TP53	0.022	0.007	-10000	0	-10000	0	0
PPP5C	0.02	0.004	-10000	0	-10000	0	0
KRT17	0.39	0.16	0.47	191	-10000	0	191
KRT14	0.28	0.13	0.36	183	-10000	0	183
TBP	0.021	0.006	-10000	0	-10000	0	0
CREBBP	-0.084	0.054	-10000	0	-10000	0	0
HDAC1	0.02	0.001	-10000	0	-10000	0	0
HDAC2	0.019	0.009	-10000	0	-10000	0	0
AP-1	0.33	0.18	0.42	207	-10000	0	207
MAPK14	0.018	0.009	-10000	0	-10000	0	0
MAPK10	-0.063	0.14	-10000	0	-0.29	76	76
MAPK11	0.018	0.009	-10000	0	-10000	0	0
KRT5	0.37	0.17	0.46	206	-10000	0	206
interleukin-1 receptor activity	-0.001	0.003	-10000	0	-10000	0	0
NCOA1	0.02	0.004	-10000	0	-10000	0	0
STAT1	0.021	0.004	-10000	0	-10000	0	0
CGA	0.1	0.078	0.38	4	-10000	0	4
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	-0.18	0.097	-10000	0	-0.34	35	35
MAPK3	0.018	0.01	-10000	0	-10000	0	0
MAPK1	0.019	0.009	-10000	0	-10000	0	0
ICAM1	0.11	0.12	0.31	5	-0.35	1	6
NFKB1	0.019	0.088	-10000	0	-0.19	25	25
MAPK8	0.21	0.11	0.29	169	-10000	0	169
MAPK9	0.018	0.01	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.095	0.14	-10000	0	-0.53	10	10
BAX	-0.001	0.058	-10000	0	-10000	0	0
POMC	0.13	0.12	0.49	7	-0.98	1	8
EP300	-0.085	0.055	-10000	0	-0.16	1	1
cortisol/GR alpha (dimer)/p53	-0.24	0.16	-10000	0	-0.41	96	96
proteasomal ubiquitin-dependent protein catabolic process	-0.066	0.037	-10000	0	-10000	0	0
SGK1	-0.11	0.071	-10000	0	-10000	0	0
IL13	0.2	0.12	0.42	23	-10000	0	23
IL6	0.11	0.13	0.43	9	-10000	0	9
PRKACG	-0.017	0.003	-10000	0	-10000	0	0
IL5	0.18	0.11	0.42	7	-10000	0	7
IL2	0.24	0.13	0.4	70	-10000	0	70
CDK5	0.018	0.009	-10000	0	-10000	0	0
PRKACB	0.021	0.002	-10000	0	-10000	0	0
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
IL8	0.21	0.18	0.38	124	-0.35	1	125
CDK5R1/CDK5	0.027	0.012	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	0.06	0.13	0.26	4	-0.25	22	26
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	-0.22	0.15	-10000	0	-0.38	97	97
SMARCA4	0.02	0.004	-10000	0	-10000	0	0
chromatin remodeling	-0.15	0.096	-10000	0	-0.31	20	20
NF kappa B1 p50/RelA/Cbp	-0.078	0.13	-10000	0	-0.31	39	39
JUN (dimer)	0.24	0.13	0.32	173	-0.28	1	174
YWHAH	0.02	0.003	-10000	0	-10000	0	0
VIPR1	0.099	0.084	-10000	0	-0.75	1	1
NR3C1	-0.16	0.099	-10000	0	-0.27	89	89
NR4A1	0.014	0.057	-10000	0	-0.33	7	7
TIF2/SUV420H1	0.025	0.028	-10000	0	-0.2	4	4
MAPKKK cascade	-0.092	0.13	-10000	0	-0.5	10	10
cortisol/GR alpha (dimer)/Src-1	-0.24	0.16	-10000	0	-0.4	102	102
PBX1	-0.062	0.14	-10000	0	-0.3	75	75
POU1F1	-0.063	0.12	-10000	0	-0.3	61	61
SELE	-0.003	0.36	0.32	14	-0.76	52	66
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	-0.15	0.097	-10000	0	-0.32	20	20
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	-0.22	0.15	-10000	0	-0.38	97	97
mol:cortisol	-0.16	0.087	-10000	0	-0.23	138	138
MMP1	0.18	0.19	0.44	73	-0.43	4	77

×

PDGFR-alpha signaling pathway

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
PDGFRA	-0.044	0.12	-10000	0	-0.3	54	54
PDGF/PDGFRA/CRKL	-0.023	0.092	-10000	0	-0.2	61	61
positive regulation of JUN kinase activity	0.003	0.077	-10000	0	-0.16	49	49
CRKL	0.02	0.003	-10000	0	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.026	0.091	-10000	0	-0.2	62	62
AP1	-0.095	0.19	0.29	1	-0.73	22	23
mol:IP3	-0.057	0.077	-10000	0	-0.21	57	57
PLCG1	-0.058	0.078	-10000	0	-0.21	57	57
PDGF/PDGFRA/alphaV Integrin	-0.021	0.09	-10000	0	-0.2	59	59
RAPGEF1	0.02	0.002	-10000	0	-10000	0	0
CRK	0.019	0.006	-10000	0	-10000	0	0
mol:Ca2+	-0.057	0.077	-10000	0	-0.21	57	57
CAV3	-0.01	0.014	-10000	0	-10000	0	0
CAV1	-0.008	0.088	-10000	0	-0.29	26	26
SHC/Grb2/SOS1	0.004	0.078	-10000	0	-0.16	49	49
PDGF/PDGFRA/Shf	-0.035	0.11	-10000	0	-0.23	65	65
FOS	-0.092	0.19	0.3	3	-0.72	22	25
JUN	-0.028	0.023	-10000	0	-0.18	1	1
oligodendrocyte development	-0.021	0.09	-10000	0	-0.2	59	59
GRB2	0.02	0.005	-10000	0	-10000	0	0
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
mol:DAG	-0.057	0.077	-10000	0	-0.21	57	57
PDGF/PDGFRA	-0.044	0.12	-10000	0	-0.3	54	54
actin cytoskeleton reorganization	-0.022	0.091	-10000	0	-0.2	60	60
SRF	-0.013	0.013	-10000	0	-10000	0	0
SHC1	0.019	0.006	-10000	0	-10000	0	0
PI3K	-0.004	0.066	-10000	0	-0.17	36	36
PDGF/PDGFRA/Crk/C3G	-0.01	0.083	-10000	0	-0.17	60	60
JAK1	-0.055	0.075	-10000	0	-0.2	60	60
ELK1/SRF	-0.05	0.073	0.14	11	-0.19	52	63
SHB	0.02	0.003	-10000	0	-10000	0	0
SHF	0.002	0.073	-10000	0	-0.29	17	17
CSNK2A1	0.023	0.018	-10000	0	-10000	0	0
GO:0007205	-0.06	0.091	-10000	0	-0.24	57	57
SOS1	0.02	0.003	-10000	0	-10000	0	0
Ras protein signal transduction	0.003	0.077	-10000	0	-0.16	49	49
PDGF/PDGFRA/SHB	-0.022	0.092	-10000	0	-0.2	60	60
PDGF/PDGFRA/Caveolin-1	-0.041	0.11	-10000	0	-0.22	78	78
ITGAV	0.02	0.004	-10000	0	-10000	0	0
ELK1	-0.055	0.077	-10000	0	-0.21	51	51
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
PDGF/PDGFRA/Crk	-0.024	0.091	-10000	0	-0.2	62	62
JAK-STAT cascade	-0.055	0.075	-10000	0	-0.2	60	60
cell proliferation	-0.035	0.11	-10000	0	-0.23	65	65

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.029	0.008	-10000	0	-10000	0	0
VLDLR	0.019	0.005	-10000	0	-10000	0	0
CRKL	0.02	0.003	-10000	0	-10000	0	0
LRPAP1	0.019	0.006	-10000	0	-10000	0	0
FYN	0.015	0.04	-10000	0	-0.29	5	5
ITGA3	0.02	0.002	-10000	0	-10000	0	0
RELN/VLDLR/Fyn	-0.032	0.099	-10000	0	-0.18	94	94
MAPK8IP1/MKK7/MAP3K11/JNK1	0.047	0.037	-10000	0	-0.16	5	5
AKT1	-0.04	0.07	0.16	1	-0.17	59	60
MAP2K7	0.02	0.004	-10000	0	-10000	0	0
RAPGEF1	0.02	0.002	-10000	0	-10000	0	0
DAB1	0.005	0.03	0.29	2	-10000	0	2
RELN/LRP8/DAB1	-0.024	0.09	0.2	2	-0.16	91	93
LRPAP1/LRP8	0.027	0.01	-10000	0	-10000	0	0
RELN/LRP8/DAB1/Fyn	-0.02	0.093	0.2	2	-0.15	94	96
DAB1/alpha3/beta1 Integrin	-0.022	0.088	-10000	0	-0.15	84	84
long-term memory	-0.048	0.11	0.23	2	-0.18	113	115
DAB1/LIS1	-0.015	0.093	0.19	2	-0.15	86	88
DAB1/CRLK/C3G	-0.022	0.089	-10000	0	-0.15	87	87
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
DAB1/NCK2	-0.014	0.095	0.19	2	-0.15	87	89
ARHGEF2	0.019	0.005	-10000	0	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	-0.042	0.12	-10000	0	-0.29	53	53
CDK5R1	0.02	0.003	-10000	0	-10000	0	0
RELN	-0.084	0.14	-10000	0	-0.29	94	94
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
RELN/LRP8/Fyn	-0.032	0.1	-10000	0	-0.18	95	95
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.044	0.12	0.21	2	-0.18	117	119
MAPK8	0.018	0.026	-10000	0	-0.29	2	2
RELN/VLDLR/DAB1	-0.024	0.089	0.2	2	-0.16	88	90
ITGB1	0.02	0.003	-10000	0	-10000	0	0
MAP1B	-0.071	0.089	0.14	9	-0.18	85	94
RELN/LRP8	-0.03	0.097	-10000	0	-0.17	92	92
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.014	0.1	0.23	6	-0.16	93	99
PI3K	0.019	0.015	-10000	0	-10000	0	0
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.03	0.006	-10000	0	-10000	0	0
RAP1A	-0.057	0.083	0.25	6	-10000	0	6
PAFAH1B1	0.019	0.006	-10000	0	-10000	0	0
MAPK8IP1	0.013	0.044	-10000	0	-0.29	6	6
CRLK/C3G	0.03	0.006	-10000	0	-10000	0	0
GRIN2B	-0.005	0.042	0.29	5	-10000	0	5
NCK2	0.02	0.002	-10000	0	-10000	0	0
neuron differentiation	-0.048	0.087	-10000	0	-0.28	15	15
neuron adhesion	-0.061	0.085	0.26	6	-10000	0	6
LRP8	0.02	0.003	-10000	0	-10000	0	0
GSK3B	-0.041	0.066	-10000	0	-0.17	56	56
RELN/VLDLR/DAB1/Fyn	-0.02	0.092	0.2	2	-0.15	91	93
MAP3K11	0.02	0.003	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.034	0.075	-10000	0	-0.18	60	60
CDK5	0.02	0.004	-10000	0	-10000	0	0
MAPT	-0.004	0.028	-10000	0	-0.27	3	3
neuron migration	-0.062	0.11	0.24	3	-0.24	57	60
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.048	0.088	-10000	0	-0.29	15	15
RELN/VLDLR	-0.02	0.094	-10000	0	-0.16	89	89

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.009	0.003	-10000	0	-10000	0	0
GNB1/GNG2	-0.049	0.095	-10000	0	-0.16	129	129
regulation of S phase of mitotic cell cycle	-0.047	0.088	-10000	0	-0.19	76	76
GNAO1	0.016	0.032	-10000	0	-0.29	3	3
HRAS	0.017	0.011	-10000	0	-10000	0	0
SHBG/T-DHT	0.013	0.004	-10000	0	-10000	0	0
PELP1	0.016	0.012	-10000	0	-10000	0	0
AKT1	-0.009	0.002	-10000	0	-10000	0	0
MAP2K1	-0.064	0.083	0.15	15	-0.25	11	26
T-DHT/AR	-0.082	0.1	-10000	0	-0.2	132	132
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-0.005	22	22
GNAI2	0.019	0.006	-10000	0	-10000	0	0
GNAI3	0.02	0.002	-10000	0	-10000	0	0
GNAI1	0.019	0.019	-10000	0	-0.29	1	1
mol:GDP	-0.11	0.13	-10000	0	-0.25	124	124
cell proliferation	-0.1	0.13	0.26	1	-0.39	33	34
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
FOS	-0.1	0.2	0.26	1	-0.63	29	30
mol:Ca2+	-0.024	0.026	-10000	0	-0.06	85	85
MAPK3	-0.089	0.11	0.27	1	-0.3	30	31
MAPK1	-0.043	0.079	-10000	0	-0.26	20	20
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
mol:IP3	0	0.001	-10000	0	-0.004	20	20
cAMP biosynthetic process	0.012	0.021	0.083	1	-10000	0	1
GNG2	0.02	0.003	-10000	0	-10000	0	0
potassium channel inhibitor activity	0	0.001	-10000	0	-0.004	20	20
HRAS/GTP	-0.047	0.087	-10000	0	-0.14	124	124
actin cytoskeleton reorganization	0.019	0.016	-10000	0	-10000	0	0
SRC	0.016	0.012	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.004	20	20
PI3K	0.017	0.014	-10000	0	-10000	0	0
apoptosis	0.087	0.14	0.41	39	-10000	0	39
T-DHT/AR/PELP1	-0.063	0.094	-10000	0	-0.17	132	132
HRAS/GDP	-0.11	0.12	-10000	0	-0.28	86	86
CREB1	-0.093	0.15	-10000	0	-0.44	39	39
RAC1-CDC42/GTP	0.024	0.02	-10000	0	-10000	0	0
AR	-0.13	0.15	-10000	0	-0.29	132	132
GNB1	0.02	0.004	-10000	0	-10000	0	0
RAF1	-0.061	0.082	0.16	15	-0.22	11	26
RAC1-CDC42/GDP	-0.082	0.15	-10000	0	-0.28	79	79
T-DHT/AR/PELP1/Src	-0.05	0.092	-10000	0	-0.16	124	124
MAP2K2	-0.061	0.082	0.15	15	-0.25	11	26
T-DHT/AR/PELP1/Src/PI3K	-0.047	0.089	-10000	0	-0.19	76	76
GNAZ	-0.05	0.13	-10000	0	-0.29	66	66
SHBG	0.017	0.01	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.076	0.13	-10000	0	-0.37	29	29
mol:T-DHT	0	0.001	-10000	0	-0.004	5	5
RAC1	0.02	0.003	-10000	0	-10000	0	0
GNRH1	-0.008	0.003	-10000	0	-10000	0	0
Gi family/GTP	-0.085	0.1	-10000	0	-0.22	78	78
CDC42	0.02	0.003	-10000	0	-10000	0	0

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.047	0.088	-10000	0	-0.4	6	6
IHH	0.016	0.04	0.3	4	-0.13	5	9
SHH Np/Cholesterol/GAS1	-0.072	0.073	0.14	4	-0.16	119	123
LRPAP1	0.019	0.006	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.072	0.072	0.16	119	-0.14	4	123
SMO/beta Arrestin2	-0.089	0.16	-10000	0	-0.33	69	69
SMO	-0.09	0.15	-10000	0	-0.34	62	62
AKT1	-0.04	0.11	-10000	0	-0.48	10	10
ARRB2	0.019	0.006	-10000	0	-10000	0	0
BOC	-0.044	0.12	-10000	0	-0.29	57	57
ADRBK1	0.02	0.003	-10000	0	-10000	0	0
heart looping	-0.093	0.16	-10000	0	-0.34	65	65
STIL	-0.04	0.083	0.17	11	-0.23	6	17
DHH N/PTCH2	0.013	0.06	-10000	0	-0.2	21	21
DHH N/PTCH1	-0.036	0.093	-10000	0	-0.19	71	71
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
DHH	0.017	0.011	-10000	0	-10000	0	0
PTHLH	-0.072	0.14	-10000	0	-0.55	6	6
determination of left/right symmetry	-0.093	0.16	-10000	0	-0.34	65	65
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
skeletal system development	-0.072	0.14	-10000	0	-0.54	6	6
IHH N/Hhip	-0.027	0.1	0.2	5	-0.2	71	76
DHH N/Hhip	0.024	0.037	0.21	1	-0.2	7	8
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.093	0.16	-10000	0	-0.34	65	65
pancreas development	0.003	0.052	0.29	1	-0.29	7	8
HHAT	0.018	0.019	-10000	0	-0.29	1	1
PI3K	0.019	0.015	-10000	0	-10000	0	0
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.12	0.15	-10000	0	-0.29	130	130
somite specification	-0.093	0.16	-10000	0	-0.34	65	65
SHH Np/Cholesterol/PTCH1	-0.047	0.073	0.21	3	-0.23	7	10
SHH Np/Cholesterol/PTCH2	-0.024	0.045	0.12	8	-0.16	22	30
SHH Np/Cholesterol/Megalin	-0.01	0.04	0.16	13	-0.16	1	14
SHH	-0.012	0.039	0.18	9	-0.2	1	10
catabolic process	-0.05	0.097	-10000	0	-0.21	71	71
SMO/Vitamin D3	-0.064	0.11	0.34	1	-0.25	61	62
SHH Np/Cholesterol/Hhip	-0.016	0.035	0.13	9	-0.15	7	16
LRP2	0.018	0.039	0.29	5	-10000	0	5
receptor-mediated endocytosis	-0.064	0.11	0.29	1	-0.28	21	22
SHH Np/Cholesterol/BOC	-0.037	0.062	0.13	6	-0.16	53	59
SHH Np/Cholesterol/CDO	-0.019	0.042	0.12	8	-0.16	17	25
mesenchymal cell differentiation	0.016	0.035	0.15	7	-0.13	9	16
mol:Vitamin D3	-0.037	0.083	0.19	11	-0.23	7	18
IHH N/PTCH2	-0.038	0.11	0.19	4	-0.2	84	88
CDON	-0.001	0.072	-10000	0	-0.29	17	17
IHH N/PTCH1	-0.036	0.1	-10000	0	-0.21	71	71
Megalin/LRPAP1	0.03	0.027	0.22	5	-10000	0	5
PTCH2	-0.004	0.082	-10000	0	-0.29	22	22
SHH Np/Cholesterol	-0.01	0.015	-10000	0	-0.15	1	1
PTCH1	-0.05	0.097	-10000	0	-0.21	71	71
HHIP	0.003	0.052	0.29	1	-0.29	7	8

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.02	0.004	-10000	0	-10000	0	0
CCL5	0.02	0.003	-10000	0	-10000	0	0
SDCBP	0.02	0.004	-10000	0	-10000	0	0
FGFR/FGF2/Syndecan-1	0.1	0.1	0.26	57	-10000	0	57
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
Syndecan-1/Laminin-5	0.081	0.1	0.25	42	-0.2	1	43
Syndecan-1/Syntenin	0.087	0.1	0.25	46	-0.2	1	47
MAPK3	0.066	0.096	0.22	42	-10000	0	42
HGF/MET	0.003	0.076	0.22	1	-0.2	34	35
TGFB1/TGF beta receptor Type II	0.02	0.004	-10000	0	-10000	0	0
BSG	0.019	0.005	-10000	0	-10000	0	0
keratinocyte migration	0.081	0.1	0.25	42	-0.2	1	43
Syndecan-1/RANTES	0.089	0.1	0.25	48	-0.2	1	49
Syndecan-1/CD147	0.087	0.1	0.27	30	-10000	0	30
Syndecan-1/Syntenin/PIP2	0.081	0.098	0.23	46	-0.2	1	47
LAMA5	0.019	0.006	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	0.078	0.095	0.23	45	-0.19	1	46
MMP7	-0.001	0.078	0.29	2	-0.29	18	20
HGF	-0.016	0.1	0.29	1	-0.29	34	35
Syndecan-1/CASK	0.066	0.091	0.16	100	-0.2	1	101
Syndecan-1/HGF/MET	0.071	0.11	0.27	26	-0.22	2	28
regulation of cell adhesion	0.056	0.092	0.21	42	-10000	0	42
HPSE	0.02	0.004	-10000	0	-10000	0	0
positive regulation of cell migration	0.1	0.1	0.26	57	-10000	0	57
SDC1	0.098	0.099	0.24	59	-10000	0	59
Syndecan-1/Collagen	0.1	0.1	0.26	57	-10000	0	57
PPIB	0.02	0.003	-10000	0	-10000	0	0
MET	0.02	0.004	-10000	0	-10000	0	0
PRKACA	0.02	0.004	-10000	0	-10000	0	0
MMP9	0.062	0.1	0.29	46	-10000	0	46
MAPK1	0.068	0.096	0.22	44	-10000	0	44
homophilic cell adhesion	0.094	0.11	0.26	58	-10000	0	58
MMP1	0.08	0.12	0.29	68	-10000	0	68

×

IL23-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	0.32	0.24	0.75	37	-10000	0	37
IL23A	0.34	0.26	0.84	35	-10000	0	35
NF kappa B1 p50/RelA/I kappa B alpha	0.24	0.18	0.62	7	-10000	0	7
positive regulation of T cell mediated cytotoxicity	0.36	0.28	0.8	53	-10000	0	53
ITGA3	0.31	0.23	0.73	38	-10000	0	38
IL17F	0.28	0.21	0.54	81	-10000	0	81
IL12B	0.098	0.077	0.23	54	-10000	0	54
STAT1 (dimer)	0.3	0.22	0.69	35	-10000	0	35
CD4	0.32	0.24	0.74	40	-10000	0	40
IL23	0.3	0.24	0.76	33	-10000	0	33
IL23R	0.17	0.14	0.59	12	-10000	0	12
IL1B	0.34	0.26	0.8	46	-10000	0	46
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	0.35	0.27	0.77	58	-10000	0	58
TYK2	0.069	0.05	0.19	23	-10000	0	23
STAT4	0.02	0.004	-10000	0	-10000	0	0
STAT3	0.021	0.003	-10000	0	-10000	0	0
IL18RAP	0.011	0.022	-10000	0	-10000	0	0
IL12RB1	0.07	0.049	0.17	37	-10000	0	37
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	0.083	0.056	0.2	36	-10000	0	36
IL23R/JAK2	0.2	0.15	0.55	19	-10000	0	19
positive regulation of chronic inflammatory response	0.36	0.28	0.8	53	-10000	0	53
natural killer cell activation	-0.013	0.013	-10000	0	-0.043	29	29
JAK2	0.092	0.071	0.22	49	-10000	0	49
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
NFKB1	0.028	0.01	-10000	0	-10000	0	0
RELA	0.028	0.01	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	0.3	0.24	0.75	34	-10000	0	34
ALOX12B	0.35	0.26	0.76	49	-10000	0	49
CXCL1	0.37	0.27	0.79	55	-10000	0	55
T cell proliferation	0.36	0.28	0.8	53	-10000	0	53
NFKBIA	0.027	0.01	-10000	0	-10000	0	0
IL17A	0.26	0.2	0.5	87	-10000	0	87
PI3K	0.18	0.21	0.64	17	-10000	0	17
IFNG	0.047	0.06	0.15	54	-10000	0	54
STAT3 (dimer)	0.17	0.2	0.61	13	-10000	0	13
IL18R1	0.01	0.028	-10000	0	-0.29	1	1
IL23/IL23R/JAK2/TYK2/SOCS3	0.27	0.21	0.6	59	-10000	0	59
IL18/IL18R	0.037	0.056	0.26	3	-0.18	1	4
macrophage activation	0.023	0.027	0.057	83	-10000	0	83
TNF	0.34	0.26	0.8	40	-10000	0	40
STAT3/STAT4	0.27	0.2	0.62	24	-10000	0	24
STAT4 (dimer)	0.3	0.22	0.69	35	-10000	0	35
IL18	0.012	0.037	0.3	3	-10000	0	3
IL19	0.31	0.31	0.72	53	-0.83	8	61
STAT5A (dimer)	0.3	0.22	0.69	36	-10000	0	36
STAT1	0.02	0.004	-10000	0	-10000	0	0
SOCS3	0.02	0.004	-10000	0	-10000	0	0
CXCL9	0.34	0.26	0.79	43	-10000	0	43
MPO	0.32	0.24	0.75	38	-10000	0	38
positive regulation of humoral immune response	0.36	0.28	0.8	53	-10000	0	53
IL23/IL23R/JAK2/TYK2	0.35	0.28	0.8	53	-10000	0	53
IL6	0.32	0.24	0.74	40	-10000	0	40
STAT5A	0.02	0.002	-10000	0	-10000	0	0
IL2	-0.004	0.038	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	-0.013	0.013	-10000	0	-0.043	29	29
CD3E	0.32	0.24	0.75	37	-10000	0	37
keratinocyte proliferation	0.36	0.28	0.8	53	-10000	0	53
NOS2	0.3	0.29	0.75	37	-0.84	2	39

×

Syndecan-2-mediated signaling events

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
Syndecan-2/Fibronectin	-0.016	0.069	-10000	0	-0.16	50	50
EPHB2	0.02	0.003	-10000	0	-10000	0	0
Syndecan-2/TACI	-0.011	0.066	0.2	1	-0.16	44	45
LAMA1	0.032	0.066	0.29	15	-0.29	2	17
Syndecan-2/alpha2 ITGB1	0.009	0.069	0.2	2	-0.15	44	46
HRAS	0.02	0.005	-10000	0	-10000	0	0
Syndecan-2/CASK	-0.029	0.055	-10000	0	-0.16	44	44
ITGA5	0.018	0.026	-10000	0	-0.29	2	2
BAX	-0.034	0.048	-10000	0	-10000	0	0
EPB41	0.02	0.002	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	-0.009	0.058	-10000	0	-0.15	43	43
LAMA3	0.02	0.024	0.29	1	-0.29	1	2
EZR	0.019	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	0.019	0.019	-10000	0	-0.29	1	1
Syndecan-2/MMP2	-0.018	0.08	-10000	0	-0.19	48	48
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.029	0.014	0.22	1	-10000	0	1
dendrite morphogenesis	-0.011	0.065	-10000	0	-0.16	44	44
Syndecan-2/GM-CSF	-0.007	0.072	0.2	7	-0.16	44	51
determination of left/right symmetry	-0.036	0.067	-10000	0	-0.19	44	44
Syndecan-2/PKC delta	-0.012	0.065	-10000	0	-0.16	44	44
GNB2L1	0.02	0.004	-10000	0	-10000	0	0
MAPK3	-0.027	0.066	0.18	11	-0.15	44	55
MAPK1	-0.026	0.066	0.18	11	-0.15	42	53
Syndecan-2/RACK1	0	0.06	-10000	0	-0.14	44	44
NF1	0.02	0.004	-10000	0	-10000	0	0
FGFR/FGF/Syndecan-2	-0.036	0.067	-10000	0	-0.19	44	44
ITGA2	0.02	0.017	0.29	1	-10000	0	1
MAPK8	-0.035	0.055	-10000	0	-0.16	44	44
Syndecan-2/alpha2/beta1 Integrin	0.017	0.079	0.21	14	-0.15	41	55
Syndecan-2/Kininogen	-0.006	0.049	-10000	0	-0.17	24	24
ITGB1	0.02	0.003	-10000	0	-10000	0	0
SRC	-0.028	0.058	0.16	12	-10000	0	12
Syndecan-2/CASK/Protein 4.1	-0.01	0.059	-10000	0	-0.15	44	44
extracellular matrix organization	-0.01	0.063	-10000	0	-0.16	41	41
actin cytoskeleton reorganization	-0.016	0.069	-10000	0	-0.16	50	50
Syndecan-2/Caveolin-2/Ras	-0.001	0.065	-10000	0	-0.15	43	43
Syndecan-2/Laminin alpha3	-0.011	0.067	0.2	1	-0.17	45	46
Syndecan-2/RasGAP	0.008	0.063	-10000	0	-0.14	40	40
alpha5/beta1 Integrin	0.028	0.02	-10000	0	-0.2	2	2
PRKCD	0.019	0.006	-10000	0	-10000	0	0
Syndecan-2 dimer	-0.011	0.065	-10000	0	-0.17	44	44
GO:0007205	0.001	0	-10000	0	-10000	0	0
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	-0.038	0.042	-10000	0	-10000	0	0
RHOA	0.019	0.006	-10000	0	-10000	0	0
SDCBP	0.02	0.004	-10000	0	-10000	0	0
TNFRSF13B	0.017	0.02	0.29	1	-10000	0	1
RASA1	0.02	0.004	-10000	0	-10000	0	0
alpha2/beta1 Integrin	0.029	0.014	0.22	1	-10000	0	1
Syndecan-2/Synbindin	-0.012	0.063	-10000	0	-0.16	44	44
TGFB1	0.02	0.004	-10000	0	-10000	0	0
CASP3	-0.031	0.055	0.18	5	-0.15	37	42
FN1	0.01	0.051	-10000	0	-0.29	8	8
Syndecan-2/IL8	0.077	0.13	0.21	129	-0.13	44	173
SDC2	-0.036	0.067	-10000	0	-0.2	44	44
KNG1	-0.011	0.008	-10000	0	-10000	0	0
Syndecan-2/Neurofibromin	-0.011	0.065	-10000	0	-0.17	44	44
TRAPPC4	0.017	0.008	-10000	0	-10000	0	0
CSF2	0.024	0.043	0.29	7	-10000	0	7
Syndecan-2/TGFB1	-0.01	0.063	-10000	0	-0.17	41	41
Syndecan-2/Syntenin/PI-4-5-P2	-0.009	0.058	-10000	0	-0.15	43	43
Syndecan-2/Ezrin	-0.002	0.065	-10000	0	-0.15	44	44
PRKACA	-0.03	0.061	0.18	9	-0.15	42	51
angiogenesis	0.077	0.13	0.2	129	-0.13	44	173
MMP2	0.004	0.069	-10000	0	-0.29	15	15
IL8	0.17	0.14	0.29	159	-10000	0	159
calcineurin-NFAT signaling pathway	-0.011	0.065	0.2	1	-0.16	44	45

×

Aurora A signaling

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
Aurora A/GADD45A	-0.018	0.044	-10000	0	-0.15	4	4
BIRC5	0.28	0.071	0.29	273	-10000	0	273
NFKBIA	-0.023	0.037	0.19	2	-10000	0	2
CPEB1	-0.065	0.13	-10000	0	-0.29	74	74
AKT1	-0.023	0.036	0.19	2	-10000	0	2
NDEL1	0.019	0.006	-10000	0	-10000	0	0
Aurora A/BRCA1	-0.016	0.039	-10000	0	-0.13	3	3
NDEL1/TACC3	-0.002	0.051	-10000	0	-10000	0	0
GADD45A	0.02	0.002	-10000	0	-10000	0	0
GSK3B	-0.019	0.027	-10000	0	-10000	0	0
PAK1/Aurora A	-0.016	0.043	-10000	0	-0.15	4	4
MDM2	0.02	0.004	-10000	0	-10000	0	0
JUB	0	0	-10000	0	-10000	0	0
TPX2	0.15	0.049	0.16	286	-10000	0	286
TP53	-0.019	0.057	-10000	0	-0.22	19	19
DLG7	-0.02	0.03	0.14	2	-10000	0	2
AURKAIP1	0.02	0.004	-10000	0	-10000	0	0
ARHGEF7	0.02	0.004	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	-0.002	0.054	-10000	0	-0.14	1	1
G2/M transition of mitotic cell cycle	-0.016	0.038	-10000	0	-0.13	3	3
AURKA	-0.022	0.04	0.17	2	-10000	0	2
AURKB	0.13	0.066	0.15	254	-10000	0	254
CDC25B	-0.013	0.03	-10000	0	-0.22	1	1
G2/M transition checkpoint	-0.018	0.028	-10000	0	-0.13	4	4
mRNA polyadenylation	-0.048	0.07	-10000	0	-0.17	58	58
Aurora A/CPEB	-0.048	0.07	-10000	0	-0.17	58	58
Aurora A/TACC1/TRAP/chTOG	0.001	0.061	-10000	0	-0.26	1	1
BRCA1	0.02	0.002	-10000	0	-10000	0	0
centrosome duplication	-0.016	0.043	-10000	0	-0.15	4	4
regulation of centrosome cycle	-0.003	0.05	-10000	0	-10000	0	0
spindle assembly	0.001	0.06	-10000	0	-0.26	1	1
TDRD7	0.02	0.002	-10000	0	-10000	0	0
Aurora A/RasGAP/Survivin	0.16	0.071	0.21	135	-10000	0	135
CENPA	0.14	0.068	0.18	189	-10000	0	189
Aurora A/PP2A	-0.018	0.043	-10000	0	-0.15	4	4
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	-0.019	0.039	-10000	0	-0.17	4	4
negative regulation of DNA binding	-0.018	0.057	-10000	0	-0.22	19	19
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.029	0.007	-10000	0	-10000	0	0
RASA1	0.02	0.004	-10000	0	-10000	0	0
Ajuba/Aurora A	-0.018	0.028	-10000	0	-0.13	4	4
mitotic prometaphase	-0.024	0.029	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.022	0.04	0.17	2	-10000	0	2
TACC1	0.018	0.019	-10000	0	-0.29	1	1
TACC3	0.02	0.017	0.29	1	-10000	0	1
Aurora A/Antizyme1	-0.001	0.054	-10000	0	-0.14	1	1
Aurora A/RasGAP	-0.017	0.042	-10000	0	-0.15	3	3
OAZ1	0.019	0.005	-10000	0	-10000	0	0
RAN	0.02	0.002	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	-0.023	0.027	-10000	0	-10000	0	0
GIT1	0.02	0.003	-10000	0	-10000	0	0
GIT1/beta-PIX/PAK1	0.037	0.014	-10000	0	-10000	0	0
Importin alpha/Importin beta/TPX2	0.15	0.049	0.15	286	-10000	0	286
PPP2R5D	0.02	0.004	-10000	0	-10000	0	0
Aurora A/TPX2	0.09	0.055	0.16	73	-10000	0	73
PAK1	0.019	0.005	-10000	0	-10000	0	0
CKAP5	0.02	0.004	-10000	0	-10000	0	0

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.02	0.003	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.074	0.077	-10000	0	-0.2	41	41
NT3 (dimer)/TRKC	-0.12	0.13	-10000	0	-0.23	164	164
NT3 (dimer)/TRKB	-0.028	0.11	0.21	1	-0.2	81	82
SHC/Grb2/SOS1/GAB1/PI3K	0.005	0.021	-10000	0	-0.18	1	1
RAPGEF1	0.02	0.002	-10000	0	-10000	0	0
BDNF	0.035	0.063	0.29	16	-10000	0	16
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
DYNLT1	0.019	0.005	-10000	0	-10000	0	0
NTRK1	0.017	0.009	-10000	0	-10000	0	0
NTRK2	-0.027	0.11	0.29	1	-0.29	45	46
NTRK3	-0.16	0.15	-10000	0	-0.29	163	163
NT-4/5 (dimer)/TRKB	0.073	0.14	0.21	127	-0.16	58	185
neuron apoptosis	0.072	0.14	0.31	46	-10000	0	46
SHC 2-3/Grb2	-0.078	0.15	-10000	0	-0.33	46	46
SHC1	0.019	0.006	-10000	0	-10000	0	0
SHC2	-0.087	0.16	-10000	0	-0.39	49	49
SHC3	-0.064	0.13	-10000	0	-0.34	34	34
STAT3 (dimer)	0.022	0.003	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	-0.002	0.085	-10000	0	-0.19	49	49
RIN/GDP	-0.051	0.077	0.19	4	-0.2	6	10
GIPC1	0.02	0.004	-10000	0	-10000	0	0
KRAS	0.019	0.005	-10000	0	-10000	0	0
DNAJA3	-0.052	0.1	0.15	1	-0.2	71	72
RIN/GTP	0.012	0.003	-10000	0	-10000	0	0
CCND1	-0.016	0.004	-10000	0	-10000	0	0
MAGED1	0.018	0.026	-10000	0	-0.29	2	2
PTPN11	0.021	0.001	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.16	0.14	0.29	153	-10000	0	153
SHC/GRB2/SOS1	0.036	0.015	-10000	0	-10000	0	0
GRB2	0.02	0.005	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.045	0.1	-10000	0	-0.17	112	112
TRKA/NEDD4-2	0.027	0.01	-10000	0	-10000	0	0
ELMO1	0.019	0.018	-10000	0	-0.29	1	1
RhoG/GTP/ELMO1/DOCK1	0.026	0.013	-10000	0	-0.17	1	1
NGF	-0.11	0.15	-10000	0	-0.29	122	122
HRAS	0.02	0.005	-10000	0	-10000	0	0
DOCK1	0.02	0.003	-10000	0	-10000	0	0
GAB2	0.018	0.019	-10000	0	-0.29	1	1
RIT2	-0.017	0.003	-10000	0	-10000	0	0
RIT1	0.019	0.006	-10000	0	-10000	0	0
FRS2	0.02	0.003	-10000	0	-10000	0	0
DNM1	0.021	0.002	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.019	0.006	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.042	0.11	-10000	0	-0.2	74	74
mol:GDP	-0.073	0.1	0.24	4	-0.28	10	14
NGF (dimer)	-0.11	0.15	-10000	0	-0.29	122	122
RhoG/GDP	0.014	0.012	-10000	0	-0.2	1	1
RIT1/GDP	-0.054	0.071	0.23	1	-0.2	6	7
TIAM1	0.018	0.026	-10000	0	-0.29	2	2
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	0.014	0.086	0.22	12	-0.17	45	57
KIDINS220/CRKL/C3G	0.03	0.006	-10000	0	-10000	0	0
SHC/RasGAP	0.027	0.01	-10000	0	-10000	0	0
FRS2 family/SHP2	0.04	0.01	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0.044	0.02	-10000	0	-10000	0	0
RIT1/GTP	0.014	0.004	-10000	0	-10000	0	0
NT3 (dimer)	-0.021	0.1	-10000	0	-0.29	36	36
RAP1/GDP	-0.05	0.062	-10000	0	-0.18	6	6
KIDINS220/CRKL	0.02	0.003	-10000	0	-10000	0	0
BDNF (dimer)	0.035	0.063	0.29	16	-10000	0	16
ubiquitin-dependent protein catabolic process	-0.045	0.1	-10000	0	-0.17	112	112
Schwann cell development	-0.034	0.023	-10000	0	-10000	0	0
EHD4	0.02	0.005	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.047	0.018	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	-0.001	0.046	-10000	0	-0.19	6	6
RAP1B	0.02	0.003	-10000	0	-10000	0	0
RAP1A	0.021	0.002	-10000	0	-10000	0	0
CDC42/GTP	-0.12	0.097	0.17	4	-0.28	43	47
ABL1	0.02	0.002	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.028	0.008	-10000	0	-10000	0	0
Rap1/GTP	-0.004	0.049	-10000	0	-0.31	1	1
STAT3	0.022	0.003	-10000	0	-10000	0	0
axon guidance	-0.12	0.092	0.13	4	-0.28	43	47
MAPK3	-0.07	0.079	0.17	9	-0.16	105	114
MAPK1	-0.069	0.08	0.17	10	-0.16	105	115
CDC42/GDP	-0.051	0.078	0.2	4	-0.2	5	9
NTF3	-0.021	0.1	-10000	0	-0.29	36	36
NTF4	0.16	0.14	0.29	153	-10000	0	153
NGF (dimer)/TRKA/FAIM	-0.033	0.092	-10000	0	-0.17	84	84
PI3K	0.019	0.015	-10000	0	-10000	0	0
FRS3	0.02	0.004	-10000	0	-10000	0	0
FAIM	0.015	0.009	-10000	0	-10000	0	0
GAB1	0.02	0.003	-10000	0	-10000	0	0
RASGRF1	-0.052	0.1	0.15	2	-0.21	70	72
SOS1	0.02	0.003	-10000	0	-10000	0	0
MCF2L	-0.12	0.1	-10000	0	-0.2	160	160
RGS19	0.019	0.005	-10000	0	-10000	0	0
CDC42	0.02	0.003	-10000	0	-10000	0	0
RAS family/GTP	-0.008	0.083	0.28	1	-0.33	7	8
Rac1/GDP	-0.051	0.077	0.2	4	-0.2	6	10
NGF (dimer)/TRKA/GRIT	-0.049	0.094	-10000	0	-0.17	112	112
neuron projection morphogenesis	-0.038	0.12	-10000	0	-0.58	1	1
NGF (dimer)/TRKA/NEDD4-2	-0.045	0.1	-10000	0	-0.17	112	112
MAP2K1	-0.002	0.069	0.17	38	-10000	0	38
NGFR	0.001	0.075	-10000	0	-0.29	18	18
NGF (dimer)/TRKA/GIPC/GAIP	-0.063	0.096	-10000	0	-0.19	105	105
RAS family/GTP/PI3K	0.003	0.022	-10000	0	-0.17	2	2
FRS2 family/SHP2/GRB2/SOS1	0.054	0.021	-10000	0	-10000	0	0
NRAS	0.021	0.002	-10000	0	-10000	0	0
GRB2/SOS1	0.028	0.008	-10000	0	-10000	0	0
PRKCI	0.013	0.01	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.02	0.003	-10000	0	-10000	0	0
PRKCZ	0.02	0.004	-10000	0	-10000	0	0
MAPKKK cascade	-0.18	0.24	-10000	0	-0.46	119	119
RASA1	0.02	0.004	-10000	0	-10000	0	0
TRKA/c-Abl	0.028	0.009	-10000	0	-10000	0	0
SQSTM1	0.02	0.004	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	0.024	0.083	0.22	11	-0.16	38	49
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.017	0.083	-10000	0	-0.16	70	70
MATK	0.02	0.005	-10000	0	-10000	0	0
NEDD4L	0.02	0.005	-10000	0	-10000	0	0
RAS family/GDP	-0.059	0.048	-10000	0	-0.15	20	20
NGF (dimer)/TRKA	-0.049	0.1	0.17	1	-0.21	73	74
Rac1/GTP	-0.084	0.077	-10000	0	-0.2	62	62
FRS2 family/SHP2/CRK family	0.051	0.025	-10000	0	-10000	0	0

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.019	0.018	-10000	0	-0.29	1	1
ANTXR2	-0.053	0.13	-10000	0	-0.29	69	69
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.011	0.016	-10000	0	-0.042	64	64
monocyte activation	-0.004	0.077	-10000	0	-0.35	13	13
MAP2K2	-0.024	0.13	-10000	0	-0.58	15	15
MAP2K1	-0.016	0.015	-10000	0	-0.069	1	1
MAP2K7	-0.016	0.015	-10000	0	-0.069	1	1
MAP2K6	-0.016	0.016	0.048	1	-0.069	1	2
CYAA	-0.04	0.054	-10000	0	-0.14	64	64
MAP2K4	-0.014	0.015	-10000	0	-10000	0	0
IL1B	-0.012	0.036	0.18	1	-0.11	9	10
Channel	-0.014	0.074	-10000	0	-0.15	64	64
NLRP1	-0.015	0.018	-10000	0	-0.12	2	2
CALM1	0.02	0.005	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.013	0.064	-10000	0	-0.4	7	7
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.011	0.016	0.042	64	-10000	0	64
MAPK3	-0.016	0.015	-10000	0	-0.069	1	1
MAPK1	-0.016	0.015	-10000	0	-0.069	1	1
PGR	-0.095	0.069	-10000	0	-0.14	187	187
PA/Cellular Receptors	-0.017	0.082	-10000	0	-0.17	64	64
apoptosis	-0.011	0.016	-10000	0	-0.042	64	64
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.013	0.072	-10000	0	-0.15	64	64
macrophage activation	-0.021	0.015	-10000	0	-10000	0	0
TNF	0.023	0.032	0.29	4	-10000	0	4
VCAM1	-0.004	0.077	-10000	0	-0.35	13	13
platelet activation	-0.013	0.064	-10000	0	-0.4	7	7
MAPKKK cascade	0.015	0.023	0.084	4	-0.062	7	11
IL18	-0.012	0.016	-10000	0	-0.11	1	1
negative regulation of macrophage activation	-0.011	0.016	-10000	0	-0.042	64	64
LEF	-0.011	0.017	-10000	0	-0.042	64	64
CASP1	-0.009	0.015	-10000	0	-0.042	45	45
mol:cAMP	-0.013	0.064	-10000	0	-0.4	7	7
necrosis	-0.011	0.016	-10000	0	-0.042	64	64
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.012	0.069	-10000	0	-0.14	64	64
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	0.071	0.048	0.15	5	-0.16	1	6
epithelial cell differentiation	0.14	0.071	0.18	218	-10000	0	218
CYFIP2	0.02	0.004	-10000	0	-10000	0	0
ENAH	0.029	0.071	0.15	64	-10000	0	64
EGFR	0.018	0.026	-10000	0	-0.29	2	2
EPHA2	0.02	0.003	-10000	0	-10000	0	0
MYO6	0.037	0.03	0.18	4	-10000	0	4
CTNNB1	0.019	0.006	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.038	0.013	-10000	0	-10000	0	0
AQP5	0.014	0.12	0.22	9	-0.36	24	33
CTNND1	0.02	0.002	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.036	0.029	0.18	4	-10000	0	4
regulation of calcium-dependent cell-cell adhesion	0.034	0.032	0.17	2	-10000	0	2
EGF	0.003	0.066	-10000	0	-0.29	14	14
NCKAP1	0.02	0.004	-10000	0	-10000	0	0
AQP3	0.079	0.078	0.22	21	-10000	0	21
cortical microtubule organization	0.14	0.071	0.18	218	-10000	0	218
GO:0000145	0.023	0.025	0.16	4	-10000	0	4
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.15	0.078	0.2	218	-10000	0	218
MLLT4	0.019	0.005	-10000	0	-10000	0	0
ARF6/GDP	0.003	0.015	-10000	0	-10000	0	0
ARF6	0.02	0.003	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.036	0.025	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.015	0.02	0.16	1	-10000	0	1
PVRL2	0.02	0.005	-10000	0	-10000	0	0
ZYX	0.036	0.03	0.18	4	-10000	0	4
ARF6/GTP	0.037	0.029	-10000	0	-10000	0	0
CDH1	0.26	0.097	0.29	251	-10000	0	251
EGFR/EGFR/EGF/EGF	0.085	0.069	0.21	2	-0.13	4	6
RhoA/GDP	0.12	0.062	-10000	0	-10000	0	0
actin cytoskeleton organization	0.027	0.028	0.17	4	-10000	0	4
IGF-1R heterotetramer	0.018	0.026	-10000	0	-0.29	2	2
GIT1	0.02	0.003	-10000	0	-10000	0	0
IGF1R	0.018	0.026	-10000	0	-0.29	2	2
IGF1	-0.079	0.14	-10000	0	-0.29	93	93
DIAPH1	-0.006	0.13	-10000	0	-0.53	9	9
Wnt receptor signaling pathway	-0.14	0.071	-10000	0	-0.18	218	218
RHOA	0.019	0.006	-10000	0	-10000	0	0
RhoA/GTP	0.003	0.016	-10000	0	-10000	0	0
CTNNA1	0.02	0.004	-10000	0	-10000	0	0
VCL	0.028	0.028	0.17	4	-10000	0	4
EFNA1	0.019	0.006	-10000	0	-10000	0	0
LPP	0.014	0.021	0.16	1	-10000	0	1
Ephrin A1/EPHA2	0.089	0.055	-10000	0	-10000	0	0
SEC6/SEC8	0.014	0.023	-10000	0	-10000	0	0
MGAT3	0.034	0.032	0.17	2	-10000	0	2
HGF/MET	0.072	0.081	0.23	1	-0.14	3	4
HGF	-0.016	0.1	0.29	1	-0.29	34	35
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.071	0.048	0.15	4	-0.17	1	5
actin cable formation	0.074	0.12	0.24	74	-0.23	3	77
KIAA1543	0.023	0.025	0.17	4	-10000	0	4
KIFC3	0.036	0.027	0.19	2	-10000	0	2
NCK1	0.015	0.009	-10000	0	-10000	0	0
EXOC3	0.017	0.008	-10000	0	-10000	0	0
ACTN1	0.037	0.029	0.18	4	-10000	0	4
NCK1/GIT1	0.023	0.014	-10000	0	-10000	0	0
mol:GDP	0.14	0.071	0.18	218	-10000	0	218
EXOC4	0.02	0.004	-10000	0	-10000	0	0
STX4	0.037	0.027	0.19	2	-10000	0	2
PIP5K1C	0.036	0.029	0.18	4	-10000	0	4
LIMA1	0.02	0.003	-10000	0	-10000	0	0
ABI1	0.02	0.004	-10000	0	-10000	0	0
ROCK1	0.059	0.09	0.19	78	-10000	0	78
adherens junction assembly	0.01	0.081	0.25	3	-0.45	5	8
IGF-1R heterotetramer/IGF1	0.035	0.1	-10000	0	-0.16	10	10
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.027	0.01	-10000	0	-10000	0	0
MET	0.02	0.004	-10000	0	-10000	0	0
PLEKHA7	0.036	0.03	0.18	4	-10000	0	4
mol:GTP	0.035	0.024	-10000	0	-10000	0	0
establishment of epithelial cell apical/basal polarity	0.055	0.08	0.2	57	-10000	0	57
cortical actin cytoskeleton stabilization	0.071	0.048	0.15	5	-0.16	1	6
regulation of cell-cell adhesion	0.027	0.028	0.17	4	-10000	0	4
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.071	0.048	0.15	4	-0.17	1	5

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0.058	0.071	0.17	65	-10000	0	65
adherens junction organization	0.072	0.068	0.19	19	-0.21	1	20
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.07	0.079	0.19	72	-10000	0	72
FMN1	0.07	0.062	0.19	12	-0.19	1	13
mol:IP3	0.02	0.032	0.14	6	-10000	0	6
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.083	0.065	0.2	12	-0.19	1	13
CTNNB1	-0.001	0.019	-10000	0	-10000	0	0
AKT1	0.024	0.037	0.14	8	-10000	0	8
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.095	0.083	0.24	17	-0.25	1	18
CTNND1	0.024	0.006	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.078	0.074	0.23	25	-0.18	1	26
VASP	0.068	0.062	0.19	11	-0.19	1	12
ZYX	0.072	0.059	0.19	13	-10000	0	13
JUB	0.076	0.061	0.19	12	-0.18	1	13
EGFR(dimer)	0.083	0.067	0.2	10	-0.19	1	11
E-cadherin/beta catenin-gamma catenin	0.16	0.078	0.2	226	-10000	0	226
mol:PI-3-4-5-P3	0.039	0.047	0.22	1	-10000	0	1
PIK3CA	0.013	0.012	-10000	0	-10000	0	0
PI3K	0.04	0.048	0.22	1	-10000	0	1
FYN	0.029	0.063	0.17	33	-0.22	4	37
mol:Ca2+	0.019	0.032	0.14	6	-10000	0	6
JUP	0	0.02	-10000	0	-10000	0	0
PIK3R1	0.023	0.007	-10000	0	-10000	0	0
mol:DAG	0.02	0.032	0.14	6	-10000	0	6
CDH1	0.26	0.097	0.3	251	-10000	0	251
RhoA/GDP	0.068	0.078	0.19	73	-10000	0	73
establishment of polarity of embryonic epithelium	0.07	0.064	0.2	14	-0.18	1	15
SRC	0.019	0.006	-10000	0	-10000	0	0
RAC1	0.02	0.003	-10000	0	-10000	0	0
RHOA	0.019	0.006	-10000	0	-10000	0	0
EGFR	0.018	0.026	-10000	0	-0.29	2	2
CASR	0.034	0.058	0.16	41	-10000	0	41
RhoA/GTP	0.021	0.035	-10000	0	-10000	0	0
AKT2	0.022	0.038	0.14	6	-10000	0	6
actin cable formation	0.064	0.069	0.22	17	-10000	0	17
apoptosis	-0.073	0.078	0.18	1	-0.19	71	72
CTNNA1	0.023	0.007	-10000	0	-10000	0	0
mol:GDP	0.059	0.075	0.17	79	-10000	0	79
PIP5K1A	0.066	0.062	0.18	11	-0.19	1	12
PLCG1	0.02	0.033	0.14	6	-10000	0	6
Rac1/GTP	0.081	0.064	0.19	8	-0.18	1	9
homophilic cell adhesion	0.003	0.005	-10000	0	-10000	0	0

×

LPA4-mediated signaling events

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
ADCY4	-0.025	0.041	-10000	0	-0.17	22	22
ADCY5	-0.072	0.078	-10000	0	-0.17	116	116
ADCY6	-0.014	0.003	-10000	0	-10000	0	0
ADCY7	-0.014	0.004	-10000	0	-10000	0	0
ADCY1	-0.018	0.025	-10000	0	-0.17	8	8
ADCY2	-0.081	0.079	-10000	0	-0.17	132	132
ADCY3	-0.014	0.003	-10000	0	-10000	0	0
ADCY8	-0.014	0.007	0.081	1	-10000	0	1
PRKCE	-0.009	0.002	-10000	0	-10000	0	0
ADCY9	-0.014	0.004	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	-0.028	0.1	0.2	26	-0.19	5	31

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.021	0.005	-10000	0	-10000	0	0
SVIL	0.017	0.036	-10000	0	-0.29	4	4
ZNF318	0.017	0.014	-10000	0	-10000	0	0
JMJD2C	0.004	0.019	0.11	9	-10000	0	9
T-DHT/AR/Ubc9	-0.042	0.1	0.15	1	-0.15	129	130
CARM1	0.02	0.004	-10000	0	-10000	0	0
PRDX1	0.019	0.008	-10000	0	-10000	0	0
PELP1	0.017	0.009	-10000	0	-10000	0	0
CTNNB1	0.02	0.006	-10000	0	-10000	0	0
AKT1	0.018	0.01	-10000	0	-10000	0	0
PTK2B	0.019	0.006	-10000	0	-10000	0	0
MED1	0.018	0.009	-10000	0	-10000	0	0
MAK	0.03	0.061	0.29	14	-10000	0	14
response to oxidative stress	0	0.001	-10000	0	-10000	0	0
HIP1	0.017	0.032	-10000	0	-0.29	3	3
GSN	0.021	0.004	-10000	0	-10000	0	0
NCOA2	0.015	0.036	-10000	0	-0.29	4	4
NCOA6	0.019	0.007	-10000	0	-10000	0	0
DNA-PK	0.033	0.021	-10000	0	-10000	0	0
NCOA4	0.02	0.003	-10000	0	-10000	0	0
PIAS3	0.02	0.006	-10000	0	-10000	0	0
cell proliferation	-0.004	0.1	0.24	15	-0.46	10	25
XRCC5	0.017	0.01	-10000	0	-10000	0	0
UBE3A	0.021	0.006	-10000	0	-10000	0	0
T-DHT/AR/SNURF	-0.056	0.12	0.15	1	-0.17	140	141
FHL2	-0.022	0.083	-10000	0	-0.5	5	5
RANBP9	0.02	0.006	-10000	0	-10000	0	0
JMJD1A	0.044	0.056	0.12	106	-10000	0	106
CDK6	0.019	0.005	-10000	0	-10000	0	0
TGFB1I1	-0.013	0.097	-10000	0	-0.29	32	32
T-DHT/AR/CyclinD1	-0.038	0.1	0.16	1	-0.15	123	124
XRCC6	0.018	0.01	-10000	0	-10000	0	0
T-DHT/AR	-0.018	0.12	0.3	1	-0.17	86	87
CTDSP1	0.019	0.007	-10000	0	-10000	0	0
CTDSP2	0.018	0.012	-10000	0	-10000	0	0
BRCA1	0.021	0.004	-10000	0	-10000	0	0
TCF4	0.015	0.028	-10000	0	-0.29	2	2
CDKN2A	0.27	0.082	0.29	265	-10000	0	265
SRF	0.019	0.016	-10000	0	-0.14	2	2
NKX3-1	0	0.068	0.11	60	-10000	0	60
KLK3	-0.007	0.061	-10000	0	-10000	0	0
TMF1	0.019	0.006	-10000	0	-10000	0	0
HNRNPA1	0.018	0.01	-10000	0	-10000	0	0
AOF2	0.001	0.003	-10000	0	-10000	0	0
APPL1	-0.017	0.008	-10000	0	-10000	0	0
T-DHT/AR/Caspase 8	-0.041	0.1	-10000	0	-0.15	129	129
AR	-0.069	0.14	-10000	0	-0.29	87	87
UBA3	0.019	0.006	-10000	0	-10000	0	0
PATZ1	0.018	0.01	-10000	0	-10000	0	0
PAWR	0.021	0.001	-10000	0	-10000	0	0
PRKDC	0.018	0.009	-10000	0	-10000	0	0
PA2G4	0.018	0.01	-10000	0	-10000	0	0
UBE2I	0.02	0.004	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.036	0.094	-10000	0	-0.14	129	129
RPS6KA3	0.021	0.005	-10000	0	-10000	0	0
T-DHT/AR/ARA70	-0.042	0.1	0.15	1	-0.15	129	130
LATS2	0.018	0.01	-10000	0	-10000	0	0
T-DHT/AR/PRX1	-0.036	0.094	-10000	0	-0.14	129	129
Cyclin D3/CDK11 p58	0.015	0.004	-10000	0	-10000	0	0
VAV3	0.021	0.003	-10000	0	-10000	0	0
KLK2	-0.015	0.068	0.28	3	-0.32	2	5
CASP8	0.018	0.009	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.031	0.1	0.17	1	-0.15	122	123
TMPRSS2	0.063	0.14	0.27	61	-0.33	4	65
CCND1	0.02	0.005	-10000	0	-10000	0	0
PIAS1	0.021	0.006	-10000	0	-10000	0	0
mol:T-DHT	0.009	0.012	0.059	1	-10000	0	1
CDC2L1	0	0	-10000	0	-10000	0	0
PIAS4	0.021	0.009	-10000	0	-10000	0	0
T-DHT/AR/CDK6	-0.04	0.1	-10000	0	-0.15	126	126
CMTM2	0.018	0.009	-10000	0	-10000	0	0
SNURF	-0.012	0.088	-10000	0	-0.29	26	26
ZMIZ1	0.028	0.014	-10000	0	-10000	0	0
CCND3	0.02	0.004	-10000	0	-10000	0	0
TGIF1	0.018	0.009	-10000	0	-10000	0	0
FKBP4	0.02	0.006	-10000	0	-10000	0	0

×

Thromboxane A2 receptor 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	-0.023	0.1	-10000	0	-0.29	35	35
GNB1/GNG2	-0.052	0.068	-10000	0	-0.18	54	54
AKT1	-0.052	0.096	-10000	0	-0.24	24	24
EGF	0.003	0.066	-10000	0	-0.29	14	14
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	-0.018	0.044	0.2	3	-10000	0	3
mol:Ca2+	-0.079	0.14	-10000	0	-0.3	62	62
LYN	-0.017	0.044	0.2	3	-10000	0	3
RhoA/GTP	-0.039	0.054	-10000	0	-0.13	49	49
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.086	0.15	-10000	0	-0.34	56	56
GNG2	0.02	0.003	-10000	0	-10000	0	0
ARRB2	0.019	0.006	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.046	0.15	0.27	2	-0.52	19	21
G beta5/gamma2	-0.066	0.09	-10000	0	-0.25	53	53
PRKCH	-0.091	0.16	0.25	1	-0.36	56	57
DNM1	0.021	0.002	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin3	0.016	0.039	-10000	0	-0.51	1	1
mol:GTP	-0.001	0.001	-10000	0	-10000	0	0
PTGDR	0.016	0.032	-10000	0	-0.29	3	3
G12 family/GTP	-0.077	0.13	-10000	0	-0.29	60	60
ADRBK1	0.02	0.003	-10000	0	-10000	0	0
ADRBK2	0.02	0.003	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0.025	0.008	-10000	0	-10000	0	0
mol:GDP	0.042	0.088	0.25	5	-0.19	1	6
mol:NADP	0.011	0.051	-10000	0	-0.29	8	8
RAB11A	0.02	0.003	-10000	0	-10000	0	0
PRKG1	-0.055	0.13	-10000	0	-0.29	68	68
mol:IP3	-0.1	0.17	-10000	0	-0.37	63	63
cell morphogenesis	0.025	0.008	-10000	0	-10000	0	0
PLCB2	-0.14	0.22	-10000	0	-0.5	64	64
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	0.01	0.071	0.2	7	-10000	0	7
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.018	0.041	0.2	3	-10000	0	3
RHOA	0.019	0.006	-10000	0	-10000	0	0
PTGIR	0.019	0.018	-10000	0	-0.29	1	1
PRKCB1	-0.097	0.16	-10000	0	-0.37	58	58
GNAQ	0.02	0.003	-10000	0	-10000	0	0
mol:L-citrulline	0.011	0.051	-10000	0	-0.29	8	8
TXA2/TXA2-R family	-0.13	0.22	-10000	0	-0.51	57	57
LCK	-0.018	0.044	0.2	3	-10000	0	3
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.01	0.038	-10000	0	-10000	0	0
TXA2-R family/G12 family/GDP/G beta/gamma	0.006	0.074	-10000	0	-0.39	9	9
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.004	0.038	0.15	2	-10000	0	2
MAPK14	-0.058	0.1	0.28	1	-0.23	52	53
TGM2/GTP	-0.12	0.19	-10000	0	-0.41	80	80
MAPK11	-0.06	0.099	-10000	0	-0.23	52	52
ARHGEF1	-0.051	0.074	-10000	0	-0.18	51	51
GNAI2	0.019	0.006	-10000	0	-10000	0	0
JNK cascade	-0.095	0.16	-10000	0	-0.38	56	56
RAB11/GDP	0.02	0.007	-10000	0	-10000	0	0
ICAM1	-0.068	0.12	-10000	0	-0.28	55	55
cAMP biosynthetic process	-0.097	0.16	-10000	0	-0.33	80	80
Gq family/GTP/EBP50	-0.023	0.079	0.23	5	-0.15	67	72
actin cytoskeleton reorganization	0.025	0.008	-10000	0	-10000	0	0
SRC	-0.019	0.041	0.2	3	-10000	0	3
GNB5	0.02	0.005	-10000	0	-10000	0	0
GNB1	0.02	0.004	-10000	0	-10000	0	0
EGF/EGFR	-0.001	0.059	0.18	8	-10000	0	8
VCAM1	-0.071	0.13	-10000	0	-0.3	55	55
TP beta/Gq family/GDP/G beta5/gamma2	-0.046	0.15	0.27	2	-0.52	19	21
platelet activation	-0.078	0.13	0.29	1	-0.3	53	54
PGI2/IP	0.014	0.013	-10000	0	-0.2	1	1
PRKACA	0.005	0.019	-10000	0	-0.17	3	3
Gq family/GDP/G beta5/gamma2	-0.041	0.12	0.21	1	-0.45	18	19
TXA2/TP beta/beta Arrestin2	0.003	0.039	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.013	0.021	-10000	0	-0.16	5	5
mol:DAG	-0.11	0.18	-10000	0	-0.42	59	59
EGFR	0.018	0.026	-10000	0	-0.29	2	2
TXA2/TP alpha	-0.13	0.21	-10000	0	-0.45	80	80
Gq family/GTP	-0.051	0.095	-10000	0	-0.19	80	80
YES1	-0.018	0.043	0.2	3	-10000	0	3
GNAI2/GTP	-0.022	0.025	-10000	0	-0.16	3	3
PGD2/DP	0.012	0.022	-10000	0	-0.2	3	3
SLC9A3R1	0.033	0.059	0.29	14	-10000	0	14
FYN	-0.02	0.047	0.2	3	-10000	0	3
mol:NO	0.011	0.051	-10000	0	-0.29	8	8
GNA15	0.035	0.064	0.29	17	-10000	0	17
PGK/cGMP	-0.024	0.088	-10000	0	-0.17	73	73
RhoA/GDP	0.018	0.008	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0.008	0.061	-10000	0	-0.23	3	3
NOS3	0.011	0.051	-10000	0	-0.29	8	8
RAC1	0.02	0.003	-10000	0	-10000	0	0
PRKCA	-0.092	0.15	-10000	0	-0.35	56	56
PRKCB	-0.093	0.16	0.24	1	-0.36	56	57
PRKCE	-0.09	0.15	-10000	0	-0.36	54	54
PRKCD	-0.098	0.16	-10000	0	-0.38	56	56
PRKCG	-0.097	0.17	-10000	0	-0.39	53	53
muscle contraction	-0.12	0.2	-10000	0	-0.48	57	57
PRKCZ	-0.087	0.14	-10000	0	-0.34	57	57
ARR3	-0.008	0.016	-10000	0	-10000	0	0
TXA2/TP beta	0.007	0.041	-10000	0	-0.17	3	3
PRKCQ	-0.093	0.15	-10000	0	-0.36	56	56
MAPKKK cascade	-0.12	0.2	-10000	0	-0.45	59	59
SELE	-0.082	0.15	-10000	0	-0.35	55	55
TP beta/GNAI2/GDP/G beta/gamma	0.028	0.036	-10000	0	-0.16	3	3
ROCK1	0.02	0.002	-10000	0	-10000	0	0
GNA14	-0.066	0.14	-10000	0	-0.29	81	81
chemotaxis	-0.14	0.24	-10000	0	-0.58	55	55
GNA12	0.02	0.003	-10000	0	-10000	0	0
GNA13	0.02	0.003	-10000	0	-10000	0	0
GNA11	0.019	0.019	-10000	0	-0.29	1	1
Rac1/GTP	0.014	0.002	-10000	0	-10000	0	0

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.31	0.49	-10000	0	-1.1	46	46
STAT6 (cleaved dimer)	-0.33	0.46	-10000	0	-1.1	54	54
IGHG1	-0.099	0.19	0.36	4	-10000	0	4
IGHG3	-0.32	0.46	-10000	0	-1.1	52	52
AKT1	-0.16	0.25	-10000	0	-0.8	9	9
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.1	0.2	-10000	0	-0.67	10	10
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.16	0.26	-10000	0	-0.75	15	15
THY1	-0.33	0.48	-10000	0	-1.1	51	51
MYB	0.052	0.088	0.29	34	-10000	0	34
HMGA1	0.024	0.032	0.29	4	-10000	0	4
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.18	0.28	0.45	2	-0.65	24	26
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.16	0.26	-10000	0	-0.75	15	15
SP1	0.013	0.033	-10000	0	-0.16	4	4
INPP5D	0.018	0.007	-10000	0	-10000	0	0
SOCS5	0.015	0.033	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.32	0.46	-10000	0	-1.1	53	53
SOCS1	-0.22	0.31	-10000	0	-0.71	44	44
SOCS3	-0.16	0.24	0.56	1	-0.66	6	7
FCER2	-0.28	0.4	-10000	0	-0.97	38	38
PARP14	0.017	0.008	-10000	0	-10000	0	0
CCL17	-0.32	0.49	0.63	3	-1.1	49	52
GRB2	0.02	0.005	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.14	0.24	-10000	0	-0.71	15	15
T cell proliferation	-0.33	0.47	-10000	0	-1.1	51	51
IL4R/JAK1	-0.33	0.47	-10000	0	-1.1	50	50
EGR2	-0.33	0.48	-10000	0	-1.1	46	46
JAK2	-0.017	0.056	-10000	0	-10000	0	0
JAK3	0.02	0.014	-10000	0	-10000	0	0
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
JAK1	-0.004	0.03	-10000	0	-10000	0	0
COL1A2	-0.16	0.34	-10000	0	-1.2	23	23
CCL26	-0.33	0.48	-10000	0	-1.1	50	50
IL4R	-0.35	0.51	-10000	0	-1.2	51	51
PTPN6	0.019	0.027	-10000	0	-10000	0	0
IL13RA2	-0.33	0.48	-10000	0	-1.1	50	50
IL13RA1	-0.018	0.057	-10000	0	-10000	0	0
IRF4	-0.059	0.17	0.44	1	-0.75	9	10
ARG1	-0.081	0.18	-10000	0	-0.63	8	8
CBL	-0.17	0.26	-10000	0	-0.62	23	23
GTF3A	0.021	0.008	-10000	0	-10000	0	0
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.015	0.08	0.2	4	-10000	0	4
IRF4/BCL6	-0.039	0.14	-10000	0	-0.68	9	9
CD40LG	0.022	0.011	-10000	0	-0.13	1	1
MAPK14	-0.17	0.27	-10000	0	-0.66	16	16
mitosis	-0.15	0.24	-10000	0	-0.77	8	8
STAT6	-0.36	0.55	0.65	1	-1.3	52	53
SPI1	0.021	0.01	-10000	0	-10000	0	0
RPS6KB1	-0.15	0.23	0.39	1	-0.75	8	9
STAT6 (dimer)	-0.36	0.55	0.65	1	-1.3	52	53
STAT6 (dimer)/PARP14	-0.34	0.49	-10000	0	-1.2	48	48
mast cell activation	0.007	0.014	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.15	0.25	-10000	0	-0.67	18	18
FRAP1	-0.16	0.25	-10000	0	-0.8	9	9
LTA	-0.32	0.48	0.64	1	-1.1	49	50
FES	0.02	0.004	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0.36	0.54	1.2	52	-0.64	1	53
CCL11	-0.34	0.48	-10000	0	-1.1	54	54
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.14	0.24	-10000	0	-0.75	8	8
IL2RG	0.023	0.032	0.3	3	-10000	0	3
IL10	-0.32	0.48	0.62	1	-1.1	45	46
IRS1	0.008	0.056	-10000	0	-0.29	10	10
IRS2	0.011	0.051	-10000	0	-0.29	8	8
IL4	-0.091	0.23	-10000	0	-0.98	11	11
IL5	-0.33	0.48	-10000	0	-1.1	50	50
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.27	0.41	0.56	4	-0.91	46	50
COL1A1	-0.12	0.24	-10000	0	-0.92	11	11
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.34	0.48	-10000	0	-1.2	49	49
IL2R gamma/JAK3	0.031	0.024	0.22	3	-10000	0	3
TFF3	-0.44	0.63	0.62	2	-1.4	75	77
ALOX15	-0.31	0.49	0.63	3	-1.1	49	52
MYBL1	0.02	0.004	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.37	0.45	-10000	0	-1	65	65
SHC1	0.019	0.006	-10000	0	-10000	0	0
CEBPB	0.021	0.011	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.14	0.23	0.43	1	-0.65	7	8
mol:PI-3-4-5-P3	-0.16	0.25	-10000	0	-0.8	9	9
PI3K	-0.16	0.26	-10000	0	-0.86	9	9
DOK2	0.019	0.006	-10000	0	-10000	0	0
ETS1	0.014	0.03	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.12	0.21	-10000	0	-0.66	9	9
ITGB3	-0.4	0.56	-10000	0	-1.3	63	63
PIGR	-0.46	0.63	0.62	4	-1.3	88	92
IGHE	0.042	0.062	0.18	19	-10000	0	19
MAPKKK cascade	-0.12	0.21	-10000	0	-0.64	9	9
BCL6	0.013	0.01	-10000	0	-10000	0	0
OPRM1	-0.33	0.48	-10000	0	-1.1	48	48
RETNLB	-0.3	0.48	0.62	1	-1.1	48	49
SELP	-0.6	0.68	0.62	1	-1.3	133	134
AICDA	-0.32	0.46	-10000	0	-1.1	50	50

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	-0.046	0.12	-10000	0	-0.2	103	103
fibroblast growth factor receptor signaling pathway	-0.046	0.12	-10000	0	-0.2	103	103
LAMA1	0.032	0.066	0.29	15	-0.29	2	17
PRNP	0.014	0.04	-10000	0	-0.29	5	5
GPC1/SLIT2	-0.052	0.11	-10000	0	-0.2	99	99
SMAD2	-0.018	0.028	0.17	5	-0.16	1	6
GPC1/PrPc/Cu2+	0.02	0.027	-10000	0	-0.17	5	5
GPC1/Laminin alpha1	0.033	0.046	0.22	14	-0.19	2	16
TDGF1	-0.01	0.076	0.29	1	-0.29	18	19
CRIPTO/GPC1	0.011	0.057	0.22	1	-0.2	18	19
APP/GPC1	0.026	0.011	-10000	0	-10000	0	0
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.026	0.039	0.092	1	-0.17	18	19
FLT1	0.019	0.019	-10000	0	-0.29	1	1
GPC1/TGFB/TGFBR1/TGFBR2	0.033	0.024	-10000	0	-0.17	2	2
SERPINC1	0.018	0.035	0.29	4	-10000	0	4
FYN	-0.029	0.041	0.092	1	-0.17	21	22
FGR	-0.027	0.038	0.092	1	-0.17	17	18
positive regulation of MAPKKK cascade	-0.021	0.099	0.22	4	-0.25	21	25
SLIT2	-0.089	0.15	-10000	0	-0.29	100	100
GPC1/NRG	0.052	0.068	0.22	42	-10000	0	42
NRG1	0.065	0.1	0.29	50	-10000	0	50
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.034	0.02	-10000	0	-0.17	1	1
LYN	-0.026	0.038	0.092	1	-0.17	17	18
mol:Spermine	-0.008	0.003	-10000	0	-10000	0	0
cell growth	-0.046	0.12	-10000	0	-0.2	103	103
BMP signaling pathway	-0.018	0.007	-10000	0	-10000	0	0
SRC	-0.026	0.039	0.092	1	-0.17	18	19
TGFBR1	0.02	0.003	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	0	0.098	0.29	10	-0.29	22	32
GPC1	0.018	0.007	-10000	0	-10000	0	0
TGFBR1 (dimer)	0.02	0.003	-10000	0	-10000	0	0
VEGFA	0.02	0.004	-10000	0	-10000	0	0
BLK	0.004	0.075	0.15	50	-0.17	14	64
HCK	-0.024	0.036	0.092	1	-0.17	15	16
FGF2	-0.074	0.14	-10000	0	-0.29	88	88
FGFR1	-0.021	0.1	-10000	0	-0.29	38	38
VEGFR1 homodimer	0.019	0.019	-10000	0	-0.29	1	1
TGFBR2	0.017	0.026	-10000	0	-0.29	2	2
cell death	0.026	0.011	-10000	0	-10000	0	0
ATIII/GPC1	0.026	0.023	0.22	3	-10000	0	3
PLA2G2A/GPC1	0.016	0.071	0.22	10	-0.2	22	32
LCK	-0.027	0.039	0.092	1	-0.17	18	19
neuron differentiation	0.052	0.068	0.22	42	-10000	0	42
PrPc/Cu2+	0.011	0.028	-10000	0	-0.2	5	5
APP	0.02	0.004	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.017	0.026	-10000	0	-0.29	2	2

×

HIF-2-alpha transcription factor network

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
MMP14	-0.016	0.081	-10000	0	-0.64	4	4
oxygen homeostasis	-0.011	0.012	-10000	0	-10000	0	0
TCEB2	0.02	0.004	-10000	0	-10000	0	0
TCEB1	0.02	0.004	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.041	0.082	-10000	0	-0.23	2	2
EPO	-0.16	0.19	-10000	0	-0.47	44	44
FIH (dimer)	-0.016	0.027	-10000	0	-10000	0	0
APEX1	-0.02	0.031	-10000	0	-10000	0	0
SERPINE1	-0.15	0.17	0.34	2	-0.43	40	42
FLT1	-0.16	0.27	-10000	0	-0.7	52	52
ADORA2A	-0.15	0.17	0.33	2	-0.42	44	46
germ cell development	-0.13	0.18	0.39	4	-0.42	38	42
SLC11A2	-0.15	0.18	0.34	2	-0.43	44	46
BHLHE40	-0.15	0.18	0.34	2	-0.42	44	46
HIF1AN	-0.016	0.027	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.084	0.12	0.32	1	-0.3	8	9
ETS1	-0.011	0.052	-10000	0	-10000	0	0
CITED2	-0.12	0.3	-10000	0	-0.88	38	38
KDR	-0.36	0.46	-10000	0	-0.91	117	117
PGK1	-0.15	0.18	0.34	2	-0.42	45	47
SIRT1	0.018	0.011	-10000	0	-10000	0	0
response to hypoxia	0	0.002	-10000	0	-10000	0	0
HIF2A/ARNT	-0.16	0.2	-10000	0	-0.47	44	44
EPAS1	-0.055	0.066	-10000	0	-0.22	8	8
SP1	0.021	0.003	-10000	0	-10000	0	0
ABCG2	-0.23	0.23	0.34	2	-0.46	123	125
EFNA1	-0.15	0.17	0.32	1	-0.43	44	45
FXN	-0.15	0.17	0.33	2	-0.42	45	47
POU5F1	-0.14	0.19	0.39	4	-0.43	38	42
neuron apoptosis	0.15	0.2	0.46	44	-10000	0	44
EP300	0.02	0.003	-10000	0	-10000	0	0
EGLN3	-0.016	0.026	-10000	0	-10000	0	0
EGLN2	-0.016	0.026	-10000	0	-10000	0	0
EGLN1	-0.014	0.025	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.036	0.015	-10000	0	-10000	0	0
VHL	0.019	0.005	-10000	0	-10000	0	0
ARNT	-0.018	0.029	-10000	0	-10000	0	0
SLC2A1	-0.15	0.17	0.32	3	-0.41	46	49
TWIST1	-0.18	0.2	0.33	2	-0.48	62	64
ELK1	0.01	0.035	-10000	0	-0.11	6	6
HIF2A/ARNT/Cbp/p300	-0.079	0.12	-10000	0	-0.29	7	7
VEGFA	-0.15	0.17	0.36	1	-0.42	44	45
CREBBP	0.02	0.004	-10000	0	-10000	0	0

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	-0.009	0.002	-10000	0	-10000	0	0
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.031	0.025	0.22	5	-10000	0	5
STXBP1	0.019	0.018	-10000	0	-0.29	1	1
ACh/CHRNA1	-0.012	0.058	0.2	6	-0.086	82	88
RAB3GAP2/RIMS1/UNC13B	0.039	0.026	0.21	5	-10000	0	5
mol:Ca2+	0	0	-10000	0	-10000	0	0
UniProt:P30996	0	0	-10000	0	-10000	0	0
UniProt:Q60393	0	0	-10000	0	-10000	0	0
CST086	0	0	-10000	0	-10000	0	0
RIMS1	0.006	0.042	0.29	5	-10000	0	5
mol:ACh	-0.032	0.054	0.073	14	-0.1	91	105
RAB3GAP2	0.019	0.005	-10000	0	-10000	0	0
STX1A/SNAP25/VAMP2	-0.023	0.086	0.19	4	-0.2	15	19
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	-0.012	0.058	0.2	6	-0.086	82	88
UNC13B	0.02	0.003	-10000	0	-10000	0	0
CHRNA1	0.021	0.042	0.29	6	-10000	0	6
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	-0.051	0.099	-10000	0	-0.18	90	90
SNAP25	-0.063	0.097	-10000	0	-0.21	89	89
VAMP2	0.002	0	-10000	0	-10000	0	0
SYT1	-0.11	0.15	-10000	0	-0.29	123	123
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.015	0.011	-10000	0	-0.17	1	1
STX1A/SNAP25 fragment 1/VAMP2	-0.023	0.086	0.19	4	-0.2	15	19

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	0.03	0.047	-10000	0	-0.17	14	14
alphaM/beta2 Integrin/GPIbA	0.039	0.019	0.21	1	-10000	0	1
alphaM/beta2 Integrin/proMMP-9	0.065	0.064	0.21	44	-10000	0	44
PLAUR	0.02	0.004	-10000	0	-10000	0	0
HMGB1	0.021	0.006	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Talin	0.041	0.013	-10000	0	-10000	0	0
AGER	0.021	0.006	-10000	0	-10000	0	0
RAP1A	0.021	0.002	-10000	0	-10000	0	0
SELPLG	0.021	0.001	-10000	0	-10000	0	0
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	0.053	0.029	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	0.062	0.1	0.29	46	-10000	0	46
CYR61	-0.015	0.098	-10000	0	-0.29	33	33
TLN1	0.02	0.003	-10000	0	-10000	0	0
Rap1/GTP	-0.052	0.11	-10000	0	-0.24	40	40
RHOA	0.019	0.006	-10000	0	-10000	0	0
P-selectin oligomer	-0.12	0.15	-10000	0	-0.29	128	128
MYH2	-0.075	0.14	-10000	0	-0.33	42	42
MST1R	0.099	0.12	0.29	85	-10000	0	85
leukocyte activation during inflammatory response	0.043	0.028	0.18	8	-10000	0	8
APOB	0.01	0.034	0.29	3	-10000	0	3
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	0.004	0.069	-10000	0	-0.29	15	15
JAM3	-0.013	0.091	-10000	0	-0.29	28	28
GP1BA	0.018	0.019	0.29	1	-10000	0	1
alphaM/beta2 Integrin/CTGF	-0.014	0.094	-10000	0	-0.17	75	75
alphaM/beta2 Integrin	-0.056	0.1	-10000	0	-0.28	32	32
JAM3 homodimer	-0.013	0.091	-10000	0	-0.29	28	28
ICAM2	0.009	0.057	-10000	0	-0.29	10	10
ICAM1	0.02	0.004	-10000	0	-10000	0	0
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.049	0.11	-10000	0	-0.27	35	35
cell adhesion	0.039	0.019	0.21	1	-10000	0	1
NFKB1	-0.005	0.068	0.38	4	-10000	0	4
THY1	0.017	0.008	-10000	0	-10000	0	0
RhoA/GDP	0.014	0.004	-10000	0	-10000	0	0
Lipoprotein(a)	0.029	0.029	0.19	8	-10000	0	8
alphaM/beta2 Integrin/LRP/tPA	0.04	0.046	-10000	0	-0.16	12	12
IL6	-0.007	0.069	0.28	11	-10000	0	11
ITGB2	0.021	0.006	-10000	0	-10000	0	0
elevation of cytosolic calcium ion concentration	0.048	0.021	0.24	1	-10000	0	1
alphaM/beta2 Integrin/JAM2/JAM3	-0.058	0.12	-10000	0	-0.18	132	132
JAM2	-0.12	0.15	-10000	0	-0.29	134	134
alphaM/beta2 Integrin/ICAM1	0.094	0.074	0.21	78	-10000	0	78
alphaM/beta2 Integrin/uPA/Plg	0.05	0.027	0.22	4	-10000	0	4
RhoA/GTP	-0.088	0.14	-10000	0	-0.34	45	45
positive regulation of phagocytosis	-0.038	0.087	-10000	0	-0.25	15	15
Ron/MSP	0.082	0.086	0.22	85	-10000	0	85
alphaM/beta2 Integrin/uPAR/uPA	0.05	0.021	0.24	1	-10000	0	1
alphaM/beta2 Integrin/uPAR	0.04	0.014	-10000	0	-10000	0	0
PLAU	0.021	0.016	0.29	1	-10000	0	1
PLAT	0.007	0.062	-10000	0	-0.29	12	12
actin filament polymerization	-0.085	0.13	-10000	0	-0.32	44	44
MST1	0.019	0.006	-10000	0	-10000	0	0
alphaM/beta2 Integrin/lipoprotein(a)	0.048	0.03	0.2	8	-10000	0	8
TNF	-0.013	0.064	0.35	6	-10000	0	6
RAP1B	0.02	0.003	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPA	0.042	0.018	0.24	1	-10000	0	1
fibrinolysis	0.048	0.026	0.21	4	-10000	0	4
HCK	0.019	0.006	-10000	0	-10000	0	0
dendritic cell antigen processing and presentation	-0.049	0.11	-10000	0	-0.27	35	35
VTN	-0.008	0.1	0.29	5	-0.29	29	34
alphaM/beta2 Integrin/CYR61	0.019	0.068	-10000	0	-0.17	32	32
LPA	0.01	0.042	0.29	5	-10000	0	5
LRP1	0.02	0.002	-10000	0	-10000	0	0
cell migration	0.034	0.055	0.19	3	-0.16	11	14
FN1	0.01	0.051	-10000	0	-0.29	8	8
alphaM/beta2 Integrin/Thy1	0.036	0.019	-10000	0	-10000	0	0
MPO	0.014	0.022	0.29	1	-10000	0	1
KNG1	-0.011	0.008	-10000	0	-10000	0	0
RAP1/GDP	0.027	0.005	-10000	0	-10000	0	0
ROCK1	-0.08	0.14	-10000	0	-0.33	45	45
ELA2	0	0	-10000	0	-10000	0	0
PLG	-0.007	0.034	0.29	3	-10000	0	3
CTGF	-0.063	0.14	-10000	0	-0.29	78	78
alphaM/beta2 Integrin/Hck	0.038	0.017	-10000	0	-10000	0	0
ITGAM	0.022	0.005	-10000	0	-10000	0	0
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.042	0.1	-10000	0	-0.16	124	124
HP	-0.11	0.15	-10000	0	-0.29	119	119
leukocyte adhesion	-0.06	0.11	-10000	0	-0.26	25	25
SELP	-0.12	0.15	-10000	0	-0.29	128	128

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.015	0.001	-10000	0	-10000	0	0
PRKCZ	0.02	0.004	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.02	0.005	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	0.006	0.041	-10000	0	-0.21	7	7
IRAK/TOLLIP	0.018	0.006	-10000	0	-10000	0	0
IKBKB	0.02	0.005	-10000	0	-10000	0	0
IKBKG	0.02	0.004	-10000	0	-10000	0	0
IL1 alpha/IL1R2	0.13	0.097	0.22	157	-10000	0	157
IL1A	0.16	0.14	0.29	148	-10000	0	148
IL1B	0.011	0.062	0.15	47	-10000	0	47
IRAK/TRAF6/p62/Atypical PKCs	0.026	0.026	-10000	0	-10000	0	0
IL1R2	0.033	0.057	0.29	13	-10000	0	13
IL1R1	0.017	0.031	-10000	0	-0.29	3	3
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.02	0.062	0.19	3	-0.33	4	7
TOLLIP	0.02	0.005	-10000	0	-10000	0	0
TICAM2	0.019	0.005	-10000	0	-10000	0	0
MAP3K3	0.02	0.004	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.014	0.003	-10000	0	-10000	0	0
IKK complex/ELKS	0.013	0.061	-10000	0	-0.36	2	2
JUN	-0.024	0.024	0.14	5	-10000	0	5
MAP3K7	0.02	0.004	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.037	0.046	-10000	0	-0.16	2	2
IL1 alpha/IL1R1/IL1RAP/MYD88	0.078	0.091	0.21	88	-0.16	2	90
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.08	0.09	0.21	88	-0.16	2	90
IL1 beta fragment/IL1R1/IL1RAP	0.027	0.041	0.26	1	-0.16	2	3
NFKB1	0.02	0.003	-10000	0	-10000	0	0
MAPK8	-0.021	0.026	0.15	5	-0.14	1	6
IRAK1	-0.014	0.003	-10000	0	-10000	0	0
IL1RN/IL1R1	0.17	0.087	0.22	219	-0.16	3	222
IRAK4	0.02	0.002	-10000	0	-10000	0	0
PRKCI	0.013	0.01	-10000	0	-10000	0	0
TRAF6	0.02	0.004	-10000	0	-10000	0	0
PI3K	0.019	0.015	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.011	0.043	-10000	0	-0.24	1	1
CHUK	0.02	0.003	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.027	0.041	0.26	1	-0.16	2	3
IL1 beta/IL1R2	0.034	0.04	0.2	11	-10000	0	11
IRAK/TRAF6/TAK1/TAB1/TAB2	0.024	0.008	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.011	0.04	-10000	0	-10000	0	0
IRAK3	0.012	0.051	-10000	0	-0.29	8	8
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.037	0.046	-10000	0	-0.16	2	2
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.054	0.066	0.17	42	-0.22	2	44
IL1 alpha/IL1R1/IL1RAP	0.08	0.093	0.21	96	-0.17	2	98
RELA	0.02	0.003	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.02	0.004	-10000	0	-10000	0	0
MYD88	0.019	0.005	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0.029	0.01	-10000	0	-10000	0	0
IL1RAP	0.013	0.01	-10000	0	-10000	0	0
UBE2N	0.021	0.001	-10000	0	-10000	0	0
IRAK/TRAF6	-0.014	0.034	-10000	0	-10000	0	0
CASP1	0.018	0.007	-10000	0	-10000	0	0
IL1RN/IL1R2	0.18	0.086	0.22	227	-10000	0	227
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.031	0.041	-10000	0	-0.16	2	2
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.035	0.078	-10000	0	-0.27	7	7
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
IL1RN	0.23	0.12	0.29	223	-10000	0	223
TRAF6/TAK1/TAB1/TAB2	0.028	0.008	-10000	0	-10000	0	0
MAP2K6	-0.015	0.029	0.16	7	-10000	0	7

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.003	0.071	-10000	0	-0.29	16	16
alphaV beta3 Integrin	0.003	0.073	-10000	0	-0.2	33	33
PTK2	-0.037	0.12	-10000	0	-0.32	31	31
positive regulation of JNK cascade	-0.043	0.13	-10000	0	-0.29	46	46
CDC42/GDP	-0.04	0.16	-10000	0	-0.38	37	37
Rac1/GDP	-0.037	0.15	-10000	0	-0.37	39	39
RAP1B	0.02	0.003	-10000	0	-10000	0	0
RAP1A	0.021	0.002	-10000	0	-10000	0	0
CTNNB1	0.019	0.006	-10000	0	-10000	0	0
CDC42/GTP	-0.05	0.16	-10000	0	-0.37	43	43
nectin-3/I-afadin	0.008	0.057	-10000	0	-0.2	19	19
RAPGEF1	-0.04	0.14	0.25	1	-0.38	34	35
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.045	0.15	-10000	0	-0.42	34	34
PDGFB-D/PDGFRB	0.003	0.071	-10000	0	-0.29	16	16
TLN1	-0.025	0.051	-10000	0	-0.26	9	9
Rap1/GTP	-0.028	0.1	-10000	0	-0.28	33	33
IQGAP1	0.02	0.004	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.036	0.012	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.008	0.057	-10000	0	-0.2	19	19
PVR	0.02	0.005	-10000	0	-10000	0	0
Necl-5(dimer)	0.02	0.005	-10000	0	-10000	0	0
mol:GDP	-0.055	0.18	-10000	0	-0.45	39	39
MLLT4	0.019	0.005	-10000	0	-10000	0	0
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
PI3K	0.021	0.056	-10000	0	-0.16	17	17
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.041	0.056	0.22	26	-10000	0	26
positive regulation of lamellipodium assembly	-0.024	0.11	-10000	0	-0.28	35	35
PVRL1	0.045	0.085	0.29	30	-10000	0	30
PVRL3	-0.003	0.076	-10000	0	-0.29	19	19
PVRL2	0.02	0.005	-10000	0	-10000	0	0
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
CDH1	0.26	0.097	0.29	251	-10000	0	251
CLDN1	-0.001	0.063	-10000	0	-0.29	13	13
JAM-A/CLDN1	0.014	0.058	-10000	0	-0.17	22	22
SRC	-0.046	0.16	-10000	0	-0.45	35	35
ITGB3	-0.016	0.1	-10000	0	-0.29	34	34
nectin-1(dimer)/I-afadin/I-afadin	0.041	0.056	0.22	26	-10000	0	26
FARP2	-0.076	0.22	-10000	0	-0.49	53	53
RAC1	0.02	0.003	-10000	0	-10000	0	0
CTNNA1	0.02	0.004	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.017	0.052	-10000	0	-0.17	18	18
nectin-1/I-afadin	0.041	0.056	0.22	26	-10000	0	26
nectin-2/I-afadin	0.027	0.01	-10000	0	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0.027	0.006	-10000	0	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.027	0.074	0.21	23	-0.17	19	42
CDC42/GTP/IQGAP1/filamentous actin	0.026	0.007	-10000	0	-10000	0	0
F11R	0.019	0.006	-10000	0	-10000	0	0
positive regulation of filopodium formation	-0.043	0.13	-10000	0	-0.29	46	46
alphaV/beta3 Integrin/Talin	-0.032	0.085	0.19	2	-0.26	16	18
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.027	0.01	-10000	0	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.027	0.01	-10000	0	-10000	0	0
PIP5K1C	-0.02	0.053	-10000	0	-0.18	23	23
VAV2	-0.034	0.16	-10000	0	-0.44	27	27
RAP1/GDP	-0.028	0.14	-10000	0	-0.34	37	37
ITGAV	0.02	0.004	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.018	0.051	-10000	0	-0.17	17	17
nectin-3(dimer)/I-afadin/I-afadin	0.008	0.057	-10000	0	-0.2	19	19
Rac1/GTP	-0.026	0.13	-10000	0	-0.34	32	32
PTPRM	-0.014	0.065	-10000	0	-0.21	25	25
E-cadherin/beta catenin/alpha catenin	0.13	0.1	0.32	22	-10000	0	22
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.02	0.003	-10000	0	-10000	0	0

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.02	0.005	-10000	0	-10000	0	0
LAT2	-0.04	0.086	-10000	0	-0.24	33	33
AP1	-0.012	0.13	0.26	1	-0.42	12	13
mol:PIP3	-0.035	0.12	0.25	10	-0.29	23	33
IKBKB	-0.014	0.082	0.18	16	-0.2	10	26
AKT1	0.015	0.14	0.34	27	-0.23	7	34
IKBKG	-0.012	0.086	0.19	15	-0.2	10	25
MS4A2	-0.021	0.097	-10000	0	-0.29	33	33
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.012	0.011	-10000	0	-10000	0	0
MAP3K1	0.031	0.14	0.22	73	-0.31	8	81
mol:Ca2+	-0.026	0.1	0.21	14	-0.23	23	37
LYN	0.015	0.016	-10000	0	-10000	0	0
CBLB	-0.034	0.079	-10000	0	-0.24	28	28
SHC1	0.019	0.006	-10000	0	-10000	0	0
RasGAP/p62DOK	0.035	0.025	-10000	0	-0.16	4	4
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	0.018	0.007	-10000	0	-10000	0	0
PLD2	-0.03	0.11	0.29	22	-0.19	35	57
PTPN13	-0.033	0.13	-10000	0	-0.46	12	12
PTPN11	0.015	0.02	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	0.004	0.12	0.27	17	-0.28	9	26
SYK	0.015	0.016	-10000	0	-10000	0	0
GRB2	0.02	0.005	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.029	0.11	-10000	0	-0.27	32	32
LAT	-0.04	0.086	-10000	0	-0.24	33	33
PAK2	0.031	0.14	0.23	75	-0.32	9	84
NFATC2	-0.025	0.079	-10000	0	-0.44	9	9
HRAS	-0.025	0.1	0.21	7	-0.27	25	32
GAB2	0.018	0.019	-10000	0	-0.29	1	1
PLA2G1B	-0.037	0.2	-10000	0	-0.83	18	18
Fc epsilon R1	-0.012	0.098	-10000	0	-0.19	64	64
Antigen/IgE/Fc epsilon R1	-0.009	0.088	-10000	0	-0.17	63	63
mol:GDP	-0.028	0.098	0.23	1	-0.34	12	13
JUN	0.019	0.018	-10000	0	-0.29	1	1
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.019	0.007	-10000	0	-10000	0	0
FOS	-0.003	0.082	-10000	0	-0.29	22	22
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.033	0.091	-10000	0	-0.24	33	33
CHUK	-0.017	0.08	0.19	13	-0.2	9	22
KLRG1	-0.036	0.074	-10000	0	-0.26	13	13
VAV1	-0.038	0.087	0.21	1	-0.24	32	33
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.034	0.081	-10000	0	-0.24	27	27
negative regulation of mast cell degranulation	-0.031	0.076	0.19	3	-0.26	13	16
BTK	-0.026	0.097	-10000	0	-0.34	12	12
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.047	0.1	-10000	0	-0.24	43	43
GAB2/PI3K/SHP2	-0.045	0.057	-10000	0	-0.18	30	30
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.033	0.082	-10000	0	-0.2	39	39
RAF1	-0.037	0.23	-10000	0	-0.91	18	18
Fc epsilon R1/FcgammaRIIB/SHIP	0.001	0.095	-10000	0	-0.17	60	60
FCER1G	0.016	0.019	-10000	0	-10000	0	0
FCER1A	-0.028	0.11	-10000	0	-0.3	39	39
Antigen/IgE/Fc epsilon R1/Fyn	-0.005	0.091	-10000	0	-0.17	66	66
MAPK3	-0.038	0.21	-10000	0	-0.84	18	18
MAPK1	-0.038	0.21	-10000	0	-0.84	18	18
NFKB1	0.02	0.003	-10000	0	-10000	0	0
MAPK8	-0.038	0.19	-10000	0	-0.61	19	19
DUSP1	0.014	0.04	-10000	0	-0.29	5	5
NF-kappa-B/RelA	-0.012	0.053	0.12	7	-0.14	8	15
actin cytoskeleton reorganization	-0.03	0.13	-10000	0	-0.45	14	14
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.021	0.087	-10000	0	-0.26	21	21
FER	-0.04	0.085	-10000	0	-0.24	32	32
RELA	0.02	0.003	-10000	0	-10000	0	0
ITK	-0.012	0.044	-10000	0	-0.23	8	8
SOS1	0.02	0.003	-10000	0	-10000	0	0
PLCG1	-0.018	0.11	0.25	3	-0.29	22	25
cytokine secretion	-0.015	0.032	-10000	0	-10000	0	0
SPHK1	-0.04	0.086	-10000	0	-0.24	33	33
PTK2	-0.031	0.14	-10000	0	-0.49	12	12
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.027	0.11	-10000	0	-0.27	32	32
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	-0.033	0.12	0.23	16	-0.28	25	41
MAP2K2	-0.043	0.21	-10000	0	-0.85	18	18
MAP2K1	-0.041	0.21	-10000	0	-0.85	18	18
MAP2K7	0.02	0.004	-10000	0	-10000	0	0
KLRG1/SHP2	-0.029	0.073	0.2	3	-0.23	13	16
MAP2K4	-0.073	0.29	-10000	0	-0.83	35	35
Fc epsilon R1/FcgammaRIIB	-0.001	0.097	-10000	0	-0.18	62	62
mol:Choline	-0.029	0.11	0.29	22	-0.18	35	57
SHC/Grb2/SOS1	-0.01	0.1	-10000	0	-0.25	24	24
FYN	0.015	0.04	-10000	0	-0.29	5	5
DOK1	0.02	0.003	-10000	0	-10000	0	0
PXN	-0.034	0.13	-10000	0	-0.44	14	14
HCLS1	-0.033	0.077	-10000	0	-0.24	25	25
PRKCB	-0.02	0.1	0.22	13	-0.25	13	26
FCGR2B	0.017	0.026	-10000	0	-0.29	2	2
IGHE	-0.001	0.006	-10000	0	-10000	0	0
KLRG1/SHIP	-0.032	0.077	0.19	3	-0.26	13	16
LCP2	0.02	0.004	-10000	0	-10000	0	0
PLA2G4A	-0.042	0.089	-10000	0	-0.25	35	35
RASA1	0.02	0.004	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.029	0.11	0.29	22	-0.18	35	57
IKK complex	-0.01	0.073	0.19	10	-0.16	6	16
WIPF1	0.02	0.003	-10000	0	-10000	0	0

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	0.058	0.1	0.21	59	-0.16	24	83
SMAD6-7/SMURF1	0.037	0.013	-10000	0	-10000	0	0
NOG	0.019	0.025	0.29	2	-10000	0	2
SMAD9	-0.061	0.17	-10000	0	-0.44	45	45
SMAD4	0.019	0.005	-10000	0	-10000	0	0
SMAD5	-0.032	0.093	-10000	0	-0.32	15	15
BMP7/USAG1	0.083	0.096	0.23	84	-0.2	1	85
SMAD5/SKI	-0.023	0.1	0.22	1	-0.3	16	17
SMAD1	-0.011	0.052	-10000	0	-0.25	4	4
BMP2	0.018	0.019	-10000	0	-0.29	1	1
SMAD1/SMAD1/SMAD4	0	0.059	-10000	0	-0.24	5	5
BMPR1A	0.02	0.004	-10000	0	-10000	0	0
BMPR1B	-0.007	0.09	0.29	1	-0.29	26	27
BMPR1A-1B/BAMBI	0.013	0.076	0.21	1	-0.19	35	36
AHSG	-0.011	0.008	-10000	0	-10000	0	0
CER1	-0.01	0.014	-10000	0	-10000	0	0
BMP2-4/CER1	0.026	0.045	-10000	0	-0.17	13	13
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.027	0.091	-10000	0	-0.29	18	18
BMP2-4 (homodimer)	0.018	0.048	-10000	0	-0.2	13	13
RGMB	0.02	0.004	-10000	0	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	0.025	0.065	0.21	1	-0.16	29	30
RGMA	-0.001	0.078	-10000	0	-0.29	20	20
SMURF1	0.02	0.004	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.026	0.085	-10000	0	-0.3	13	13
BMP2-4/USAG1	0.041	0.063	0.21	21	-0.17	12	33
SMAD6/SMURF1/SMAD5	-0.022	0.098	0.22	1	-0.31	14	15
SOSTDC1	0.037	0.082	0.29	26	-10000	0	26
BMP7/BMPR2/BMPR1A-1B	0.055	0.093	0.21	54	-0.16	18	72
SKI	0.02	0.004	-10000	0	-10000	0	0
BMP6 (homodimer)	0.016	0.032	-10000	0	-0.29	3	3
HFE2	-0.006	0.017	-10000	0	-10000	0	0
ZFYVE16	0.02	0.004	-10000	0	-10000	0	0
MAP3K7	0.02	0.004	-10000	0	-10000	0	0
BMP2-4/CHRD	-0.018	0.085	-10000	0	-0.19	55	55
SMAD5/SMAD5/SMAD4	-0.021	0.1	0.22	1	-0.31	14	15
MAPK1	0.02	0.002	-10000	0	-10000	0	0
TAK1/TAB family	-0.012	0.086	-10000	0	-0.26	13	13
BMP7 (homodimer)	0.082	0.12	0.29	68	-0.29	1	69
NUP214	0.02	0.002	-10000	0	-10000	0	0
BMP6/FETUA	0.016	0.019	-10000	0	-0.2	1	1
SMAD1/SKI	-0.005	0.061	-10000	0	-0.25	6	6
SMAD6	0.02	0.003	-10000	0	-10000	0	0
CTDSP2	0.02	0.002	-10000	0	-10000	0	0
BMP2-4/FETUA	0.019	0.036	-10000	0	-0.17	7	7
MAP3K7IP1	0	0	-10000	0	-10000	0	0
GREM1	0.015	0.04	-10000	0	-0.29	5	5
BMPR2 (homodimer)	0.019	0.005	-10000	0	-10000	0	0
GADD34/PP1CA	0.038	0.013	-10000	0	-10000	0	0
BMPR1A-1B (homodimer)	0.009	0.068	0.22	1	-0.2	26	27
CHRDL1	-0.23	0.12	-10000	0	-0.29	229	229
ENDOFIN/SMAD1	-0.003	0.06	-10000	0	-0.25	6	6
SMAD6-7/SMURF1/SMAD1	0.009	0.065	-10000	0	-0.25	5	5
SMAD6/SMURF1	0.02	0.004	-10000	0	-10000	0	0
BAMBI	0.007	0.062	-10000	0	-0.29	12	12
SMURF2	0.02	0.003	-10000	0	-10000	0	0
BMP2-4/CHRDL1	-0.13	0.094	-10000	0	-0.18	217	217
BMP2-4/GREM1	0.025	0.052	-10000	0	-0.18	16	16
SMAD7	0.02	0.004	-10000	0	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.057	0.17	-10000	0	-0.41	49	49
SMAD1/SMAD6	-0.004	0.06	-10000	0	-0.25	6	6
TAK1/SMAD6	0.028	0.008	-10000	0	-10000	0	0
BMP7	0.082	0.12	0.29	68	-0.29	1	69
BMP6	0.017	0.032	-10000	0	-0.29	3	3
MAP3K7IP2	0	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.023	0.091	0.2	1	-0.3	16	17
PPM1A	0.02	0.003	-10000	0	-10000	0	0
SMAD1/SMURF2	-0.005	0.061	-10000	0	-0.26	6	6
SMAD7/SMURF1	0.028	0.009	-10000	0	-10000	0	0
CTDSPL	0.019	0.005	-10000	0	-10000	0	0
PPP1CA	0.02	0.004	-10000	0	-10000	0	0
XIAP	0.021	0.002	-10000	0	-10000	0	0
CTDSP1	0.018	0.006	-10000	0	-10000	0	0
PPP1R15A	0.02	0.004	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.032	0.1	-10000	0	-0.34	18	18
CHRD	-0.045	0.12	-10000	0	-0.29	55	55
BMPR2	0.019	0.005	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.033	0.085	-10000	0	-0.31	14	14
BMP4	0.007	0.062	-10000	0	-0.29	12	12
FST	0.02	0.068	0.29	9	-0.29	7	16
BMP2-4/NOG	0.028	0.046	0.21	1	-0.17	13	14
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	0.059	0.091	-10000	0	-0.16	17	17

×

Canonical Wnt signaling 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.045	0.037	0.22	3	-10000	0	3
AES	0.038	0.03	0.18	2	-10000	0	2
FBXW11	0.02	0.004	-10000	0	-10000	0	0
mol:GTP	0.001	0.002	-10000	0	-10000	0	0
LRP6/FZD1	0.028	0.009	-10000	0	-10000	0	0
SMAD4	0.019	0.005	-10000	0	-10000	0	0
DKK2	0.015	0.044	0.29	1	-0.29	5	6
TLE1	0.04	0.03	0.19	2	-10000	0	2
MACF1	0.021	0.002	-10000	0	-10000	0	0
CTNNB1	0.052	0.11	0.29	17	-0.38	3	20
WIF1	-0.035	0.12	0.29	3	-0.29	51	54
beta catenin/RanBP3	0.12	0.16	0.36	82	-10000	0	82
KREMEN2	0.18	0.14	0.29	168	-10000	0	168
DKK1	0.006	0.076	0.29	3	-0.29	16	19
beta catenin/beta TrCP1	0.061	0.1	0.28	17	-0.38	2	19
FZD1	0.02	0.005	-10000	0	-10000	0	0
AXIN2	-0.37	0.55	0.54	5	-1.1	96	101
AXIN1	0.021	0.004	-10000	0	-10000	0	0
RAN	0.021	0.003	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.024	0.091	-10000	0	-0.56	6	6
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.019	0.12	-10000	0	-0.51	8	8
Axin1/APC/GSK3	0.011	0.056	0.19	2	-0.25	3	5
Axin1/APC/GSK3/beta catenin/Macf1	0.017	0.092	0.31	6	-0.4	6	12
HNF1A	0.044	0.04	0.25	5	-10000	0	5
CTBP1	0.037	0.032	0.19	2	-10000	0	2
MYC	-0.042	0.21	0.56	13	-1	5	18
RANBP3	0.021	0.005	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.12	0.093	0.21	150	-0.12	5	155
NKD1	0.019	0.042	0.29	3	-0.29	3	6
TCF4	0.038	0.032	0.2	2	-10000	0	2
TCF3	0.038	0.032	0.19	2	-10000	0	2
WNT1/LRP6/FZD1/Axin1	0.047	0.018	-10000	0	-10000	0	0
Ran/GTP	0.017	0.004	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.1	0.2	0.4	79	-0.37	1	80
LEF1	0.041	0.033	0.2	3	-10000	0	3
DVL1	0.025	0.047	0.23	1	-0.23	2	3
CSNK2A1	0.02	0.005	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	-0.044	0.15	0.27	1	-0.45	18	19
DKK1/LRP6/Kremen 2	0.12	0.11	0.21	151	-0.15	15	166
LRP6	0.02	0.005	-10000	0	-10000	0	0
CSNK1A1	0.043	0.038	0.23	3	-10000	0	3
NLK	0.005	0.022	-10000	0	-10000	0	0
CCND1	-0.059	0.11	0.48	1	-0.62	2	3
WNT1	0.019	0.019	0.29	1	-10000	0	1
GSK3A	0.02	0.004	-10000	0	-10000	0	0
GSK3B	0.016	0.008	-10000	0	-10000	0	0
FRAT1	0.019	0.006	-10000	0	-10000	0	0
PPP2R5D	0.02	0.062	0.2	3	-0.26	7	10
APC	-0.014	0.051	0.19	15	-10000	0	15
WNT1/LRP6/FZD1	0.025	0.055	0.17	8	-0.27	1	9
CREBBP	0.04	0.033	0.2	3	-10000	0	3

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.003	0.071	-10000	0	-0.29	16	16
mol:S1P	-0.001	0.005	-10000	0	-10000	0	0
S1P1/S1P/Gi	-0.049	0.091	-10000	0	-0.19	72	72
GNAO1	0.014	0.034	-10000	0	-0.29	3	3
S1P/S1P3/G12/G13	0.015	0.062	-10000	0	-0.16	31	31
AKT1	-0.062	0.16	-10000	0	-0.48	33	33
AKT3	-0.077	0.23	-10000	0	-0.84	21	21
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.003	0.071	-10000	0	-0.29	16	16
GNAI2	0.017	0.014	-10000	0	-10000	0	0
GNAI3	0.018	0.012	-10000	0	-10000	0	0
GNAI1	0.016	0.022	-10000	0	-0.29	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
S1PR3	-0.016	0.098	-10000	0	-0.29	32	32
S1PR2	0.02	0.004	-10000	0	-10000	0	0
EDG1	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.063	0.12	-10000	0	-0.34	33	33
MAPK3	-0.071	0.11	-10000	0	-0.33	33	33
MAPK1	-0.07	0.11	-10000	0	-0.33	33	33
JAK2	-0.067	0.13	-10000	0	-0.33	36	36
CXCR4	-0.071	0.11	-10000	0	-0.33	33	33
FLT1	0.016	0.025	-10000	0	-0.3	1	1
RhoA/GDP	0.014	0.004	-10000	0	-10000	0	0
Rac1/GDP	0.015	0.002	-10000	0	-10000	0	0
SRC	-0.067	0.11	-10000	0	-0.32	32	32
S1P/S1P3/Gi	-0.064	0.12	-10000	0	-0.34	33	33
RAC1	0.02	0.003	-10000	0	-10000	0	0
RhoA/GTP	-0.06	0.12	-10000	0	-0.3	36	36
VEGFA	0.017	0.016	-10000	0	-10000	0	0
S1P/S1P2/Gi	-0.039	0.091	-10000	0	-0.28	17	17
VEGFR1 homodimer/VEGFA homodimer	0.024	0.027	-10000	0	-0.22	1	1
RHOA	0.019	0.006	-10000	0	-10000	0	0
S1P/S1P3/Gq	-0.058	0.12	-10000	0	-0.22	90	90
GNAQ	0.02	0.003	-10000	0	-10000	0	0
GNAZ	-0.052	0.13	-10000	0	-0.29	66	66
G12/G13	0.029	0.006	-10000	0	-10000	0	0
GNA14	-0.066	0.14	-10000	0	-0.29	81	81
GNA15	0.035	0.064	0.29	17	-10000	0	17
GNA12	0.02	0.003	-10000	0	-10000	0	0
GNA13	0.02	0.003	-10000	0	-10000	0	0
GNA11	0.019	0.019	-10000	0	-0.29	1	1
Rac1/GTP	-0.061	0.12	-10000	0	-0.3	36	36

×

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

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
MAP4K1	-0.035	0.12	0.23	1	-0.37	26	27
CRKL	-0.043	0.12	-10000	0	-0.38	29	29
HRAS	-0.02	0.11	-10000	0	-0.33	24	24
mol:PIP3	0.001	0.12	0.26	2	-0.33	26	28
SPRED1	0.02	0.004	-10000	0	-10000	0	0
SPRED2	0.02	0.003	-10000	0	-10000	0	0
GAB1	-0.038	0.12	-10000	0	-0.4	29	29
FOXO3	-0.025	0.13	-10000	0	-0.36	28	28
AKT1	-0.023	0.13	-10000	0	-0.38	28	28
BAD	-0.026	0.13	-10000	0	-0.36	28	28
megakaryocyte differentiation	-0.04	0.12	-10000	0	-0.38	29	29
GSK3B	0.006	0.14	0.33	4	-0.36	23	27
RAF1	-0.02	0.094	0.22	3	-0.28	23	26
SHC1	0.019	0.006	-10000	0	-10000	0	0
STAT3	-0.039	0.12	-10000	0	-0.4	28	28
STAT1	-0.093	0.28	-10000	0	-0.86	32	32
HRAS/SPRED1	-0.008	0.096	-10000	0	-0.28	22	22
cell proliferation	-0.04	0.12	-10000	0	-0.39	29	29
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
TEC	0.019	0.005	-10000	0	-10000	0	0
RPS6KB1	-0.025	0.13	-10000	0	-0.39	29	29
HRAS/SPRED2	-0.008	0.095	-10000	0	-0.28	22	22
LYN/TEC/p62DOK	-0.006	0.13	-10000	0	-0.38	27	27
MAPK3	-0.016	0.074	0.19	3	-0.21	14	17
STAP1	-0.037	0.12	-10000	0	-0.4	29	29
GRAP2	0.02	0.003	-10000	0	-10000	0	0
JAK2	-0.078	0.24	-10000	0	-0.74	32	32
STAT1 (dimer)	-0.092	0.27	-10000	0	-0.85	32	32
mol:Gleevec	0.002	0.005	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.01	0.13	-10000	0	-0.39	27	27
actin filament polymerization	-0.038	0.12	-10000	0	-0.39	29	29
LYN	0.02	0.004	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.055	0.18	-10000	0	-0.55	30	30
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.024	0.12	-10000	0	-0.36	28	28
PI3K	-0.014	0.11	-10000	0	-0.37	20	20
PTEN	0.019	0.005	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.096	0.33	-10000	0	-1	29	29
MAPK8	-0.04	0.12	-10000	0	-0.4	29	29
STAT3 (dimer)	-0.039	0.12	-10000	0	-0.39	28	28
positive regulation of transcription	-0.012	0.063	0.18	3	-0.21	3	6
mol:GDP	-0.02	0.11	-10000	0	-0.34	23	23
PIK3C2B	-0.038	0.12	-10000	0	-0.4	28	28
CBL/CRKL	-0.031	0.12	-10000	0	-0.37	28	28
FER	-0.038	0.12	-10000	0	-0.4	29	29
SH2B3	-0.039	0.12	-10000	0	-0.4	29	29
PDPK1	0.001	0.12	0.29	4	-0.32	26	30
SNAI2	-0.044	0.13	-10000	0	-0.41	28	28
positive regulation of cell proliferation	-0.067	0.21	-10000	0	-0.67	30	30
KITLG	0.01	0.024	-10000	0	-10000	0	0
cell motility	-0.067	0.21	-10000	0	-0.67	30	30
PTPN6	0.019	0.014	-10000	0	-10000	0	0
EPOR	-0.024	0.14	-10000	0	-0.69	7	7
STAT5A (dimer)	-0.052	0.18	-10000	0	-0.56	30	30
SOCS1	0.02	0.005	-10000	0	-10000	0	0
cell migration	0.039	0.12	0.39	29	-10000	0	29
SOS1	0.02	0.003	-10000	0	-10000	0	0
EPO	-0.006	0.079	-10000	0	-0.3	19	19
VAV1	0.02	0.004	-10000	0	-10000	0	0
GRB10	-0.04	0.12	-10000	0	-0.4	29	29
PTPN11	0.019	0.013	-10000	0	-10000	0	0
SCF/KIT	-0.035	0.13	-10000	0	-0.41	29	29
GO:0007205	0.002	0.007	-10000	0	-10000	0	0
MAP2K1	-0.019	0.078	0.2	3	-0.22	22	25
CBL	0.017	0.008	-10000	0	-10000	0	0
KIT	-0.11	0.34	-10000	0	-1	32	32
MAP2K2	-0.019	0.077	0.2	3	-0.23	21	24
SHC/Grb2/SOS1	-0.008	0.13	-10000	0	-0.39	25	25
STAT5A	-0.055	0.18	-10000	0	-0.57	30	30
GRB2	0.02	0.005	-10000	0	-10000	0	0
response to radiation	-0.044	0.13	-10000	0	-0.4	29	29
SHC/GRAP2	0.028	0.009	-10000	0	-10000	0	0
PTPRO	-0.039	0.12	-10000	0	-0.4	28	28
SH2B2	-0.038	0.12	-10000	0	-0.4	28	28
DOK1	0.02	0.003	-10000	0	-10000	0	0
MATK	-0.039	0.12	-10000	0	-0.4	29	29
CREBBP	0.007	0.043	-10000	0	-10000	0	0
BCL2	-0.055	0.23	-10000	0	-0.91	15	15

×

S1P5 pathway

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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.009	0.09	0.23	10	-10000	0	10
GNAI2	0.019	0.006	-10000	0	-10000	0	0
S1P/S1P5/G12	0.078	0.078	0.19	90	-10000	0	90
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.016	0.032	-10000	0	-0.29	3	3
RhoA/GTP	-0.009	0.092	-10000	0	-0.23	10	10
negative regulation of cAMP metabolic process	-0.01	0.093	0.17	2	-0.22	17	19
GNAZ	-0.05	0.13	-10000	0	-0.29	66	66
GNAI3	0.02	0.002	-10000	0	-10000	0	0
GNA12	0.02	0.003	-10000	0	-10000	0	0
S1PR5	0.11	0.13	0.29	93	-10000	0	93
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.01	0.093	0.17	2	-0.22	17	19
RhoA/GDP	0.014	0.004	-10000	0	-10000	0	0
RHOA	0.019	0.006	-10000	0	-10000	0	0
GNAI1	0.019	0.019	-10000	0	-0.29	1	1

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	0.005	0.12	0.26	12	-0.29	28	40
FYN	-0.011	0.13	0.24	15	-0.31	30	45
LAT/GRAP2/SLP76	-0.004	0.12	0.24	7	-0.28	31	38
IKBKB	0.02	0.005	-10000	0	-10000	0	0
AKT1	-0.011	0.11	0.23	12	-0.26	32	44
B2M	0.018	0.011	-10000	0	-10000	0	0
IKBKG	-0.009	0.042	0.11	9	-0.099	9	18
MAP3K8	0.02	0.004	-10000	0	-10000	0	0
mol:Ca2+	-0.011	0.014	0.019	4	-0.045	3	7
integrin-mediated signaling pathway	0.026	0.007	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.018	0.14	0.25	10	-0.33	32	42
TRPV6	0.029	0.11	1.2	2	-10000	0	2
CD28	0.018	0.02	-10000	0	-0.29	1	1
SHC1	-0.015	0.13	0.25	13	-0.32	33	46
receptor internalization	-0.034	0.14	0.17	5	-0.35	45	50
PRF1	-0.025	0.15	-10000	0	-0.66	8	8
KRAS	0.019	0.005	-10000	0	-10000	0	0
GRB2	0.02	0.005	-10000	0	-10000	0	0
COT/AKT1	-0.007	0.099	0.21	12	-0.22	30	42
LAT	-0.022	0.13	0.21	5	-0.31	36	41
EntrezGene:6955	0.001	0.002	-10000	0	-10000	0	0
CD3D	0.019	0.018	0.3	1	-10000	0	1
CD3E	0.018	0.008	-10000	0	-10000	0	0
CD3G	0.019	0.018	0.3	1	-10000	0	1
RASGRP2	-0.019	0.05	-10000	0	-0.15	33	33
RASGRP1	-0.015	0.12	0.28	6	-0.27	28	34
HLA-A	0	0.002	-10000	0	-10000	0	0
RASSF5	0.019	0.005	-10000	0	-10000	0	0
RAP1A/GTP/RAPL	0.026	0.007	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.003	0.052	0.16	11	-0.11	6	17
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.03	0.044	-10000	0	-0.14	31	31
PRKCA	-0.018	0.066	0.15	6	-0.17	21	27
GRAP2	0.02	0.003	-10000	0	-10000	0	0
mol:IP3	-0.036	0.077	-10000	0	-0.23	30	30
EntrezGene:6957	0.001	0.002	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.017	0.086	0.13	1	-0.28	27	28
ORAI1	-0.034	0.092	-10000	0	-1	2	2
CSK	-0.019	0.12	0.2	11	-0.31	33	44
B7 family/CD28	-0.004	0.098	-10000	0	-0.26	29	29
CHUK	0.02	0.003	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.034	0.12	0.17	1	-0.33	36	37
PTPN6	-0.015	0.12	0.2	9	-0.3	33	42
VAV1	-0.02	0.13	0.2	9	-0.31	36	45
Monovalent TCR/CD3	0.01	0.01	-10000	0	-10000	0	0
CBL	0.017	0.008	-10000	0	-10000	0	0
LCK	-0.006	0.12	0.24	17	-0.29	29	46
PAG1	-0.019	0.12	0.19	11	-0.32	33	44
RAP1A	0.021	0.002	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.029	0.12	0.18	4	-0.32	36	40
CD80	0.015	0.011	-10000	0	-10000	0	0
CD86	0.015	0.011	-10000	0	-10000	0	0
PDK1/CARD11/BCL10/MALT1	-0.028	0.055	-10000	0	-0.17	31	31
HRAS	0.02	0.005	-10000	0	-10000	0	0
GO:0035030	-0.028	0.078	0.18	1	-0.23	30	31
CD8A	0.018	0.02	0.3	1	-10000	0	1
CD8B	0.021	0.042	0.29	5	-0.3	1	6
PTPRC	0.016	0.021	-10000	0	-0.29	1	1
PDK1/PKC theta	-0.019	0.13	0.29	9	-0.3	31	40
CSK/PAG1	-0.012	0.12	0.24	10	-0.31	31	41
SOS1	0.02	0.003	-10000	0	-10000	0	0
peptide-MHC class I	0.014	0.01	-10000	0	-10000	0	0
GRAP2/SLP76	-0.001	0.13	0.22	4	-0.31	33	37
STIM1	-0.015	0.022	-10000	0	-10000	0	0
RAS family/GTP	0.006	0.072	0.19	11	-0.17	14	25
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.034	0.15	0.17	3	-0.37	43	46
mol:DAG	-0.04	0.064	-10000	0	-0.21	31	31
RAP1A/GDP	0.003	0.026	0.094	6	-10000	0	6
PLCG1	0.019	0.005	-10000	0	-10000	0	0
CD247	0.02	0.006	-10000	0	-10000	0	0
cytotoxic T cell degranulation	-0.024	0.14	-10000	0	-0.64	8	8
RAP1A/GTP	-0.009	0.019	-10000	0	-0.06	33	33
mol:PI-3-4-5-P3	-0.013	0.12	0.24	10	-0.29	32	42
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.016	0.1	-10000	0	-0.28	30	30
NRAS	0.021	0.002	-10000	0	-10000	0	0
ZAP70	0.021	0.002	-10000	0	-10000	0	0
GRB2/SOS1	0.028	0.008	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.028	0.11	0.21	1	-0.28	32	33
MALT1	0.02	0.005	-10000	0	-10000	0	0
TRAF6	0.02	0.004	-10000	0	-10000	0	0
CD8 heterodimer	0.034	0.031	0.22	6	-0.21	1	7
CARD11	0.02	0.003	-10000	0	-10000	0	0
PRKCB	-0.018	0.065	0.15	5	-0.17	21	26
PRKCE	-0.018	0.064	0.15	5	-0.17	21	26
PRKCQ	-0.021	0.13	0.27	7	-0.32	32	39
LCP2	0.02	0.004	-10000	0	-10000	0	0
BCL10	0.021	0.002	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.008	0.1	0.22	12	-0.22	32	44
IKK complex	0.004	0.056	0.16	17	-0.096	1	18
RAS family/GDP	-0.006	0.009	-10000	0	-0.035	2	2
MAP3K14	-0.011	0.076	0.17	10	-0.18	29	39
PDPK1	-0.011	0.11	0.24	12	-0.25	31	43
TCR/CD3/MHC I/CD8/Fyn	-0.04	0.15	-10000	0	-0.38	39	39

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	0.026	0.007	-10000	0	-10000	0	0
cell-cell adhesion	0.042	0.047	0.16	32	-10000	0	32
Ephrin B/EPHB2/RasGAP	0.019	0.077	-10000	0	-0.16	43	43
ITSN1	0.02	0.004	-10000	0	-10000	0	0
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
SHC1	0.019	0.006	-10000	0	-10000	0	0
Ephrin B1/EPHB3	0.018	0.013	-10000	0	-10000	0	0
Ephrin B1/EPHB1	0.011	0.043	-10000	0	-0.17	15	15
HRAS/GDP	-0.043	0.094	-10000	0	-0.2	43	43
Ephrin B/EPHB1/GRB7	0.01	0.081	0.21	1	-0.16	41	42
Endophilin/SYNJ1	-0.036	0.052	0.16	7	-10000	0	7
KRAS	0.019	0.005	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	0.007	0.076	-10000	0	-0.16	40	40
endothelial cell migration	0.025	0.022	-10000	0	-10000	0	0
GRB2	0.02	0.005	-10000	0	-10000	0	0
GRB7	0.021	0.023	0.29	2	-10000	0	2
PAK1	-0.01	0.092	0.21	8	-0.27	2	10
HRAS	0.02	0.005	-10000	0	-10000	0	0
RRAS	-0.037	0.054	0.16	7	-10000	0	7
DNM1	0.021	0.002	-10000	0	-10000	0	0
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.003	0.097	0.16	57	-0.27	3	60
lamellipodium assembly	-0.042	0.047	-10000	0	-0.16	32	32
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.018	0.074	-10000	0	-0.22	18	18
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
EPHB2	0.02	0.003	-10000	0	-10000	0	0
EPHB3	0.013	0.01	-10000	0	-10000	0	0
EPHB1	-0.001	0.068	-10000	0	-0.29	15	15
EPHB4	0.02	0.005	-10000	0	-10000	0	0
mol:GDP	-0.045	0.079	0.14	2	-0.22	34	36
Ephrin B/EPHB2	0.013	0.07	-10000	0	-0.15	43	43
Ephrin B/EPHB3	0.01	0.056	-10000	0	-0.15	27	27
JNK cascade	0.06	0.17	0.34	75	-10000	0	75
Ephrin B/EPHB1	0.002	0.072	-10000	0	-0.16	43	43
RAP1/GDP	-0.062	0.085	-10000	0	-0.24	19	19
EFNB2	0.02	0.004	-10000	0	-10000	0	0
EFNB3	-0.028	0.11	-10000	0	-0.29	44	44
EFNB1	0.02	0.002	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	0.018	0.044	-10000	0	-0.16	15	15
RAP1B	0.02	0.003	-10000	0	-10000	0	0
RAP1A	0.021	0.002	-10000	0	-10000	0	0
CDC42/GTP	-0.011	0.08	-10000	0	-0.2	33	33
Rap1/GTP	-0.046	0.05	-10000	0	-0.16	34	34
axon guidance	0.026	0.007	-10000	0	-10000	0	0
MAPK3	-0.031	0.067	0.17	1	-0.25	8	9
MAPK1	-0.031	0.066	0.17	1	-0.25	8	9
Rac1/GDP	-0.062	0.085	-10000	0	-0.24	20	20
actin cytoskeleton reorganization	-0.056	0.062	-10000	0	-0.18	35	35
CDC42/GDP	-0.063	0.086	-10000	0	-0.24	20	20
PI3K	0.028	0.024	-10000	0	-10000	0	0
EFNA5	0.02	0.005	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.026	0.008	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	-0.031	0.08	-10000	0	-0.19	48	48
CDC42	0.02	0.003	-10000	0	-10000	0	0
RAS family/GTP	-0.046	0.05	-10000	0	-0.16	34	34
PTK2	0.013	0.11	0.54	12	-10000	0	12
MAP4K4	0.06	0.17	0.34	75	-10000	0	75
SRC	0.019	0.006	-10000	0	-10000	0	0
KALRN	0.002	0.064	-10000	0	-0.29	13	13
Intersectin/N-WASP	0.028	0.008	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.013	0.12	0.26	38	-0.24	6	44
MAP2K1	-0.025	0.068	-10000	0	-0.21	18	18
WASL	0.02	0.005	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	0.027	0.05	-10000	0	-0.16	15	15
cell migration	-0.027	0.11	0.24	4	-0.28	14	18
NRAS	0.021	0.002	-10000	0	-10000	0	0
SYNJ1	-0.036	0.053	0.16	7	-10000	0	7
PXN	0.021	0.001	-10000	0	-10000	0	0
TF	-0.029	0.051	0.15	5	-10000	0	5
HRAS/GTP	-0.003	0.066	-10000	0	-0.15	40	40
Ephrin B1/EPHB1-2	0.019	0.044	-10000	0	-0.16	15	15
cell adhesion mediated by integrin	0.012	0.059	0.15	23	-0.24	4	27
RAC1	0.02	0.003	-10000	0	-10000	0	0
mol:GTP	-0.002	0.068	0.18	1	-0.15	43	44
RAC1-CDC42/GTP	-0.04	0.049	-10000	0	-0.16	28	28
RASA1	0.02	0.004	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.062	0.086	-10000	0	-0.24	18	18
ruffle organization	-0.014	0.092	0.29	4	-0.25	3	7
NCK1	0.015	0.009	-10000	0	-10000	0	0
receptor internalization	-0.039	0.05	0.15	7	-10000	0	7
Ephrin B/EPHB2/KALRN	0.009	0.077	-10000	0	-0.16	42	42
ROCK1	0.047	0.091	0.17	100	-10000	0	100
RAS family/GDP	-0.062	0.062	-10000	0	-0.18	36	36
Rac1/GTP	-0.043	0.049	-10000	0	-0.16	36	36
Ephrin B/EPHB1/Src/Paxillin	-0.026	0.076	-10000	0	-0.2	42	42

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.11	0.15	-10000	0	-0.29	120	120
oxygen homeostasis	0	0	-10000	0	-10000	0	0
TCEB2	0.02	0.004	-10000	0	-10000	0	0
TCEB1	0.02	0.004	-10000	0	-10000	0	0
HIF1A/p53	0.014	0.054	-10000	0	-0.25	8	8
HIF1A	-0.003	0.047	-10000	0	-0.28	7	7
COPS5	0.02	0.004	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.05	0.026	-10000	0	-10000	0	0
FIH (dimer)	0.02	0.003	-10000	0	-10000	0	0
CDKN2A	0.27	0.082	0.29	265	-10000	0	265
ARNT/IPAS	-0.06	0.11	-10000	0	-0.2	109	109
HIF1AN	0.02	0.003	-10000	0	-10000	0	0
GNB2L1	0.02	0.004	-10000	0	-10000	0	0
HIF1A/ARNT	0.01	0.054	0.25	1	-0.26	8	9
CUL2	0.02	0.004	-10000	0	-10000	0	0
OS9	0.02	0.002	-10000	0	-10000	0	0
RACK1/Elongin B/Elongin C	0.037	0.013	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF1A/Hsp90	0.015	0.054	0.25	1	-0.27	7	8
PHD1-3/OS9	0.046	0.018	-10000	0	-10000	0	0
HIF1A/RACK1/Elongin B/Elongin C	0.029	0.056	-10000	0	-0.26	8	8
VHL	0.019	0.005	-10000	0	-10000	0	0
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
HIF1A/JAB1	0.014	0.057	0.25	1	-0.26	8	9
EGLN3	0.02	0.004	-10000	0	-10000	0	0
EGLN2	0.02	0.004	-10000	0	-10000	0	0
EGLN1	0.019	0.005	-10000	0	-10000	0	0
TP53	0.019	0.006	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	-0.01	0.14	-10000	0	-0.52	19	19
ARNT	0.019	0.006	-10000	0	-10000	0	0
ARD1A	0	0	-10000	0	-10000	0	0
RBX1	0.02	0.003	-10000	0	-10000	0	0
HIF1A/p19ARF	0.16	0.088	0.26	36	-0.23	7	43

×

Arf6 signaling events

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
CENTA1/KIF3B	0.026	0.016	0.19	2	-10000	0	2
ARNO/beta Arrestin1-2	0.01	0.097	-10000	0	-0.77	4	4
EGFR	0.018	0.026	-10000	0	-0.29	2	2
EPHA2	0.02	0.003	-10000	0	-10000	0	0
USP6	0.019	0.006	-10000	0	-10000	0	0
IQSEC1	0.019	0.005	-10000	0	-10000	0	0
EGFR/EGFR/EGF/EGF	0.017	0.052	-10000	0	-0.2	15	15
ARRB2	0.005	0.002	-10000	0	-10000	0	0
mol:GTP	0.033	0.057	0.12	65	-0.12	4	69
ARRB1	0.02	0.005	-10000	0	-10000	0	0
FBXO8	0.02	0.005	-10000	0	-10000	0	0
TSHR	0.016	0.021	0.29	1	-10000	0	1
EGF	0.003	0.066	-10000	0	-0.29	14	14
somatostatin receptor activity	0	0	0.001	8	-0.001	44	52
ARAP2	0.019	0.005	-10000	0	-10000	0	0
mol:GDP	-0.052	0.095	0.14	1	-0.23	37	38
mol:PI-3-4-5-P3	0	0	0.001	2	-0.001	11	13
ITGA2B	0.019	0.03	0.29	1	-0.29	2	3
ARF6	0.02	0.003	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.036	0.025	-10000	0	-10000	0	0
ADAP1	0.022	0.023	0.29	2	-10000	0	2
KIF13B	0.019	0.006	-10000	0	-10000	0	0
HGF/MET	0.002	0.076	0.22	1	-0.2	34	35
PXN	0.021	0.001	-10000	0	-10000	0	0
ARF6/GTP	-0.057	0.1	0.22	4	-0.22	45	49
EGFR/EGFR/EGF/EGF/ARFGEP100	0.026	0.048	-10000	0	-0.17	15	15
ADRB2	0.015	0.04	-10000	0	-0.29	5	5
receptor agonist activity	0	0	0	6	0	36	42
actin filament binding	0	0	0	6	0	46	52
SRC	0.019	0.006	-10000	0	-10000	0	0
ITGB3	-0.016	0.1	-10000	0	-0.29	34	34
GNAQ	0.02	0.003	-10000	0	-10000	0	0
EFA6/PI-4-5-P2	0	0	0.001	10	-0.001	23	33
ARF6/GDP	0.001	0.13	0.22	16	-0.33	19	35
ARF6/GDP/GULP/ACAP1	-0.065	0.11	-10000	0	-0.26	39	39
alphaIIb/beta3 Integrin/paxillin/GIT1	0.026	0.072	0.21	1	-0.17	35	36
ACAP1	0.019	0.006	-10000	0	-10000	0	0
ACAP2	0.013	0.01	-10000	0	-10000	0	0
LHCGR/beta Arrestin2	0.009	0.02	-10000	0	-10000	0	0
EFNA1	0.019	0.006	-10000	0	-10000	0	0
HGF	-0.016	0.1	0.29	1	-0.29	34	35
CYTH3	-0.009	0.001	-10000	0	-10000	0	0
CYTH2	0	0.12	-10000	0	-0.97	4	4
NCK1	0.015	0.009	-10000	0	-10000	0	0
fibronectin binding	0	0	0.001	6	0	28	34
endosomal lumen acidification	0	0	0	9	0	48	57
microtubule-based process	0	0	-10000	0	-10000	0	0
GULP1	-0.043	0.12	-10000	0	-0.29	59	59
GNAQ/ARNO	0.011	0.11	-10000	0	-0.9	4	4
mol:Phosphatidic acid	0	0	0	1	-10000	0	1
PIP3-E	0	0	0	4	0	1	5
MET	0.02	0.004	-10000	0	-10000	0	0
GNA14	-0.066	0.14	-10000	0	-0.29	81	81
GNA15	0.035	0.064	0.29	17	-10000	0	17
GIT1	0.02	0.003	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	0.001	12	-0.001	28	40
GNA11	0.018	0.019	-10000	0	-0.29	1	1
LHCGR	-0.009	0.015	-10000	0	-10000	0	0
AGTR1	-0.094	0.14	-10000	0	-0.29	99	99
desensitization of G-protein coupled receptor protein signaling pathway	0.009	0.02	-10000	0	-10000	0	0
IPCEF1/ARNO	0.013	0.1	-10000	0	-0.78	4	4
alphaIIb/beta3 Integrin	0.002	0.079	0.22	1	-0.21	35	36

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.04	0.11	-10000	0	-0.2	87	87
PDGFRB	-0.004	0.072	-10000	0	-0.29	16	16
SPHK1	-0.008	0.079	-10000	0	-0.59	5	5
mol:S1P	-0.012	0.07	-10000	0	-0.48	5	5
S1P1/S1P/Gi	-0.061	0.12	0.3	3	-0.3	31	34
GNAO1	0.016	0.032	-10000	0	-0.29	3	3
PDGFB-D/PDGFRB/PLCgamma1	-0.06	0.12	0.26	3	-0.3	25	28
PLCG1	-0.065	0.1	0.26	2	-0.32	19	21
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.004	0.071	-10000	0	-0.29	16	16
GNAI2	0.019	0.01	-10000	0	-10000	0	0
GNAI3	0.018	0.012	-10000	0	-10000	0	0
GNAI1	0.017	0.021	-10000	0	-0.29	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	-0.057	0.07	-10000	0	-0.16	87	87
S1P1/S1P	-0.049	0.081	0.24	1	-0.31	7	8
negative regulation of cAMP metabolic process	-0.06	0.12	0.3	3	-0.29	31	34
MAPK3	-0.062	0.12	0.37	3	-0.34	15	18
calcium-dependent phospholipase C activity	-0.001	0.002	-10000	0	-10000	0	0
Rac1/GDP	0.015	0.002	-10000	0	-10000	0	0
RhoA/GDP	0.014	0.004	-10000	0	-10000	0	0
KDR	-0.072	0.14	-10000	0	-0.29	87	87
PLCB2	-0.043	0.085	0.26	5	-0.28	7	12
RAC1	0.02	0.003	-10000	0	-10000	0	0
RhoA/GTP	-0.05	0.066	-10000	0	-0.27	7	7
receptor internalization	-0.049	0.073	-10000	0	-0.29	7	7
PTGS2	-0.055	0.12	0.38	3	-0.43	1	4
Rac1/GTP	-0.05	0.066	-10000	0	-0.27	7	7
RHOA	0.019	0.006	-10000	0	-10000	0	0
VEGFA	0.02	0.004	-10000	0	-10000	0	0
negative regulation of T cell proliferation	-0.06	0.12	0.3	3	-0.29	31	34
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	-0.052	0.13	-10000	0	-0.29	66	66
MAPK1	-0.063	0.11	0.32	3	-0.34	15	18
S1P1/S1P/PDGFB-D/PDGFRB	-0.057	0.093	0.24	3	-0.29	14	17
ABCC1	0.01	0.018	-10000	0	-10000	0	0

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
GNAO1	0.016	0.032	-10000	0	-0.29	3	3
CDC42/GTP	-0.035	0.089	-10000	0	-0.26	15	15
PLCG1	-0.042	0.077	-10000	0	-0.24	18	18
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.019	0.006	-10000	0	-10000	0	0
GNAI3	0.02	0.002	-10000	0	-10000	0	0
G12/G13	0.029	0.006	-10000	0	-10000	0	0
cell migration	-0.035	0.087	-10000	0	-0.26	15	15
S1PR5	0.11	0.13	0.29	93	-10000	0	93
S1PR4	0.02	0.005	-10000	0	-10000	0	0
MAPK3	-0.043	0.078	-10000	0	-0.24	18	18
MAPK1	-0.042	0.077	-10000	0	-0.25	15	15
S1P/S1P5/Gi	-0.01	0.093	0.17	2	-0.22	17	19
GNAI1	0.019	0.019	-10000	0	-0.29	1	1
CDC42/GDP	0.015	0.003	-10000	0	-10000	0	0
S1P/S1P5/G12	0.078	0.078	0.19	90	-10000	0	90
RHOA	-0.015	0.035	0.17	10	-10000	0	10
S1P/S1P4/Gi	-0.034	0.086	-10000	0	-0.18	69	69
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	-0.05	0.13	-10000	0	-0.29	66	66
S1P/S1P4/G12/G13	0.036	0.012	-10000	0	-10000	0	0
GNA12	0.02	0.003	-10000	0	-10000	0	0
GNA13	0.02	0.003	-10000	0	-10000	0	0
CDC42	0.02	0.003	-10000	0	-10000	0	0

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.02	0.004	-10000	0	-10000	0	0
SPHK1	0.02	0.004	-10000	0	-10000	0	0
GNAI2	0.019	0.006	-10000	0	-10000	0	0
mol:S1P	0.005	0.002	-10000	0	-10000	0	0
GNAO1	0.016	0.032	-10000	0	-0.29	3	3
mol:Sphinganine-1-P	-0.017	0.005	-10000	0	-10000	0	0
growth factor activity	0	0	-10000	0	-10000	0	0
S1P/S1P2/G12/G13	0.039	0.031	-10000	0	-10000	0	0
GNAI3	0.02	0.002	-10000	0	-10000	0	0
G12/G13	0.029	0.006	-10000	0	-10000	0	0
S1PR3	-0.014	0.097	-10000	0	-0.29	32	32
S1PR2	0.02	0.004	-10000	0	-10000	0	0
EDG1	0	0	-10000	0	-10000	0	0
S1P1/S1P	0	0.019	-10000	0	-10000	0	0
S1PR5	0.11	0.13	0.29	93	-10000	0	93
S1PR4	0.02	0.005	-10000	0	-10000	0	0
GNAI1	0.019	0.019	-10000	0	-0.29	1	1
S1P/S1P5/G12	0.081	0.083	0.2	85	-10000	0	85
S1P/S1P3/Gq	-0.06	0.13	0.19	1	-0.26	68	69
S1P/S1P4/Gi	-0.034	0.089	-10000	0	-0.26	17	17
GNAQ	0.02	0.003	-10000	0	-10000	0	0
GNAZ	-0.05	0.13	-10000	0	-0.29	66	66
GNA14	-0.066	0.14	-10000	0	-0.29	81	81
GNA15	0.035	0.064	0.29	17	-10000	0	17
GNA12	0.02	0.003	-10000	0	-10000	0	0
GNA13	0.02	0.003	-10000	0	-10000	0	0
GNA11	0.019	0.019	-10000	0	-0.29	1	1
ABCC1	0.02	0.004	-10000	0	-10000	0	0

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.023	0.055	-10000	0	-0.18	18	18
NF kappa B1 p50/RelA/I kappa B alpha	-0.003	0.067	0.23	3	-0.3	1	4
AP1	0.035	0.081	0.18	6	-0.15	38	44
mol:PIP3	-0.024	0.031	-10000	0	-0.15	10	10
AKT1	0.004	0.096	0.27	7	-0.27	3	10
PTK2B	-0.025	0.079	-10000	0	-0.28	16	16
RHOA	-0.03	0.081	-10000	0	-0.29	22	22
PIK3CB	0.015	0.009	-10000	0	-10000	0	0
mol:Ca2+	-0.022	0.051	0.2	4	-0.17	1	5
MAGI3	0.02	0.002	-10000	0	-10000	0	0
RELA	0.021	0.003	-10000	0	-10000	0	0
apoptosis	-0.002	0.048	-10000	0	-0.18	15	15
HRAS/GDP	0.015	0.003	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.001	0.1	0.23	9	-0.29	8	17
NF kappa B1 p50/RelA	0.02	0.09	0.18	10	-0.24	6	16
endothelial cell migration	-0.032	0.087	-10000	0	-0.38	16	16
ADCY4	-0.046	0.097	-10000	0	-0.31	26	26
ADCY5	-0.083	0.11	-10000	0	-0.28	49	49
ADCY6	-0.037	0.078	-10000	0	-0.26	21	21
ADCY7	-0.036	0.075	-10000	0	-0.26	19	19
ADCY1	-0.042	0.087	-10000	0	-0.27	26	26
ADCY2	-0.092	0.11	-10000	0	-0.28	52	52
ADCY3	-0.036	0.077	-10000	0	-0.26	21	21
ADCY8	-0.033	0.074	-10000	0	-0.26	19	19
ADCY9	-0.038	0.079	-10000	0	-0.26	22	22
GSK3B	0.005	0.1	0.19	34	-0.26	13	47
arachidonic acid secretion	-0.046	0.081	-10000	0	-0.27	22	22
GNG2	0.018	0.009	-10000	0	-10000	0	0
TRIP6	0.008	0.011	-10000	0	-10000	0	0
GNAO1	-0.023	0.045	-10000	0	-0.19	19	19
HRAS	0.02	0.005	-10000	0	-10000	0	0
NFKBIA	-0.016	0.06	0.22	3	-0.28	2	5
GAB1	0.02	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	0.004	0.16	-10000	0	-0.81	11	11
JUN	0.019	0.019	-10000	0	-0.29	1	1
LPA/LPA2/NHERF2	0.023	0.024	-10000	0	-10000	0	0
TIAM1	-0.014	0.18	-10000	0	-0.93	11	11
PIK3R1	0.018	0.008	-10000	0	-10000	0	0
mol:IP3	-0.02	0.044	0.18	3	-10000	0	3
PLCB3	-0.015	0.032	0.17	7	-10000	0	7
FOS	-0.003	0.082	-10000	0	-0.29	22	22
positive regulation of mitosis	-0.046	0.081	-10000	0	-0.27	22	22
LPA/LPA1-2-3	0.036	0.063	0.2	10	-0.17	18	28
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0	-10000	0	-10000	0	0
BCAR1	0.02	0.004	-10000	0	-10000	0	0
stress fiber formation	-0.011	0.066	-10000	0	-0.28	8	8
GNAZ	-0.055	0.077	-10000	0	-0.18	74	74
EGFR/PI3K-beta/Gab1	-0.007	0.041	-10000	0	-0.16	9	9
positive regulation of dendritic cell cytokine production	0.035	0.062	0.2	10	-0.17	18	28
LPA/LPA2/MAGI-3	0.023	0.024	-10000	0	-10000	0	0
ARHGEF1	-0.022	0.055	0.18	12	-0.17	13	25
GNAI2	-0.021	0.041	-10000	0	-0.19	15	15
GNAI3	-0.023	0.044	-10000	0	-0.19	18	18
GNAI1	-0.022	0.041	-10000	0	-0.18	17	17
LPA/LPA3	0.019	0.043	0.19	12	-0.088	13	25
LPA/LPA2	0.011	0.023	-10000	0	-0.089	1	1
LPA/LPA1	0.002	0.059	-10000	0	-0.22	18	18
HB-EGF/EGFR	0.022	0.049	0.12	44	-0.17	1	45
HBEGF	0.009	0.059	0.15	44	-10000	0	44
mol:DAG	-0.02	0.044	0.18	3	-10000	0	3
cAMP biosynthetic process	-0.061	0.086	0.2	3	-0.26	23	26
NFKB1	0.02	0.003	-10000	0	-10000	0	0
SRC	0.019	0.006	-10000	0	-10000	0	0
GNB1	0.018	0.009	-10000	0	-10000	0	0
LYN	-0.016	0.059	0.31	1	-0.3	2	3
GNAQ	0.001	0.027	0.2	1	-10000	0	1
LPAR2	0.021	0.004	-10000	0	-10000	0	0
LPAR3	0.032	0.055	0.3	12	-10000	0	12
LPAR1	0.008	0.053	-10000	0	-0.18	18	18
IL8	0.12	0.16	0.27	112	-0.34	5	117
PTK2	-0.018	0.046	0.18	7	-0.17	10	17
Rac1/GDP	0.015	0.002	-10000	0	-10000	0	0
CASP3	-0.002	0.048	-10000	0	-0.18	15	15
EGFR	0.019	0.026	-10000	0	-0.29	2	2
PLCG1	-0.016	0.043	0.12	1	-0.16	3	4
PLD2	-0.019	0.05	0.18	8	-0.17	14	22
G12/G13	0.026	0.052	-10000	0	-0.17	17	17
PI3K-beta	-0.032	0.056	-10000	0	-0.22	13	13
cell migration	0.004	0.06	-10000	0	-0.25	11	11
SLC9A3R2	0.02	0.004	-10000	0	-10000	0	0
PXN	-0.012	0.067	-10000	0	-0.28	8	8
HRAS/GTP	-0.048	0.081	-10000	0	-0.27	22	22
RAC1	0.02	0.003	-10000	0	-10000	0	0
MMP9	0.063	0.1	0.3	46	-10000	0	46
PRKCE	0.019	0.006	-10000	0	-10000	0	0
PRKCD	-0.023	0.048	0.18	4	-10000	0	4
Gi(beta/gamma)	-0.041	0.076	-10000	0	-0.24	21	21
mol:LPA	-0.005	0.028	-10000	0	-0.13	14	14
TRIP6/p130 Cas/FAK1/Paxillin	0.006	0.067	0.2	1	-0.29	4	5
MAPKKK cascade	-0.046	0.081	-10000	0	-0.27	22	22
contractile ring contraction involved in cytokinesis	-0.028	0.082	-10000	0	-0.29	22	22
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.045	0.08	-10000	0	-0.18	73	73
GNA15	0.008	0.041	0.14	18	-10000	0	18
GNA12	0.02	0.004	-10000	0	-10000	0	0
GNA13	0.02	0.004	-10000	0	-10000	0	0
MAPT	-0.002	0.1	0.24	8	-0.3	8	16
GNA11	0	0.029	0.2	1	-0.18	1	2
Rac1/GTP	0.003	0.17	-10000	0	-0.85	11	11
MMP2	-0.032	0.087	-10000	0	-0.39	16	16

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.02	0.004	-10000	0	-10000	0	0
VLDLR	0.019	0.005	-10000	0	-10000	0	0
LRPAP1	0.019	0.006	-10000	0	-10000	0	0
NUDC	0.02	0.003	-10000	0	-10000	0	0
RELN/LRP8	-0.03	0.097	-10000	0	-0.17	92	92
CaM/Ca2+	0.015	0.003	-10000	0	-10000	0	0
KATNA1	0.02	0.004	-10000	0	-10000	0	0
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	-0.062	0.07	0.17	4	-0.16	80	84
IQGAP1/CaM	0.028	0.009	-10000	0	-10000	0	0
DAB1	0.005	0.03	0.29	2	-10000	0	2
IQGAP1	0.02	0.004	-10000	0	-10000	0	0
PLA2G7	0.033	0.059	0.29	14	-10000	0	14
CALM1	0.02	0.005	-10000	0	-10000	0	0
DYNLT1	0.019	0.005	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	0.027	0.01	-10000	0	-10000	0	0
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0.021	0.002	-10000	0	-10000	0	0
CDK5R1	0.02	0.003	-10000	0	-10000	0	0
LIS1/Poliovirus Protein 3A	-0.013	0.005	-10000	0	-10000	0	0
CDK5R2	0.011	0.048	0.29	7	-10000	0	7
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.028	0.098	0.21	2	-0.17	88	90
YWHAE	0.019	0.006	-10000	0	-10000	0	0
NDEL1/14-3-3 E	-0.062	0.068	0.16	4	-0.2	5	9
MAP1B	-0.019	0.064	-10000	0	-0.21	30	30
RAC1	0.004	0.002	-10000	0	-10000	0	0
p35/CDK5	-0.063	0.064	0.16	5	-10000	0	5
RELN	-0.084	0.14	-10000	0	-0.29	94	94
PAFAH/LIS1	-0.008	0.048	0.2	14	-10000	0	14
LIS1/CLIP170	-0.019	0.008	-10000	0	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.068	0.057	-10000	0	-0.2	1	1
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.036	0.083	0.2	1	-0.19	31	32
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	-0.057	0.069	0.15	5	-0.2	10	15
LIS1/IQGAP1	-0.018	0.008	-10000	0	-10000	0	0
RHOA	0.004	0.002	-10000	0	-10000	0	0
PAFAH1B1	-0.016	0.007	-10000	0	-10000	0	0
PAFAH1B3	0.02	0.004	-10000	0	-10000	0	0
PAFAH1B2	0.017	0.008	-10000	0	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	-0.008	0.055	-10000	0	-0.15	27	27
NDEL1/Katanin 60/Dynein heavy chain	-0.067	0.068	-10000	0	-0.22	2	2
LRP8	0.02	0.003	-10000	0	-10000	0	0
NDEL1/Katanin 60	-0.064	0.068	0.16	4	-0.21	7	11
P39/CDK5	-0.058	0.073	0.16	11	-10000	0	11
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	-0.019	0.008	-10000	0	-10000	0	0
CDK5	-0.063	0.066	0.16	4	-0.16	80	84
PPP2R5D	0.02	0.004	-10000	0	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	-0.015	0.006	-10000	0	-10000	0	0
CSNK2A1	0.019	0.005	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.023	0.088	0.25	2	-0.16	84	86
RELN/VLDLR	-0.02	0.094	-10000	0	-0.16	89	89
CDC42	0.004	0.002	-10000	0	-10000	0	0

×

Signaling events mediated by PTP1B

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
PDGFRB	0.003	0.071	-10000	0	-0.29	16	16
Jak2/Leptin Receptor	-0.14	0.14	-10000	0	-0.34	51	51
PTP1B/AKT1	-0.017	0.079	0.21	2	-0.26	12	14
FYN	0.015	0.04	-10000	0	-0.29	5	5
p210 bcr-abl/PTP1B	-0.027	0.08	0.23	2	-0.26	14	16
EGFR	0.013	0.03	-10000	0	-0.3	2	2
EGF/EGFR	-0.012	0.083	0.2	1	-0.28	10	11
CSF1	0.018	0.026	-10000	0	-0.29	2	2
AKT1	0.015	0.014	-10000	0	-10000	0	0
INSR	0.016	0.013	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.026	0.092	0.23	2	-0.28	18	20
Insulin Receptor/Insulin	-0.006	0.083	0.22	1	-0.29	7	8
HCK	0.019	0.006	-10000	0	-10000	0	0
CRK	0.019	0.006	-10000	0	-10000	0	0
TYK2	-0.027	0.077	0.2	4	-0.29	8	12
EGF	0.002	0.068	-10000	0	-0.3	14	14
YES1	0.02	0.005	-10000	0	-10000	0	0
CAV1	-0.035	0.087	0.2	1	-0.26	19	20
TXN	0.018	0.019	0.3	1	-10000	0	1
PTP1B/IRS1/GRB2	-0.017	0.082	-10000	0	-0.27	11	11
cell migration	0.027	0.08	0.26	14	-0.23	2	16
STAT3	0.02	0.006	-10000	0	-10000	0	0
PRLR	-0.11	0.15	-10000	0	-0.29	123	123
ITGA2B	0.015	0.033	0.29	1	-0.29	2	3
CSF1R	0.018	0.026	-10000	0	-0.29	2	2
Prolactin Receptor/Prolactin	-0.11	0.13	-10000	0	-0.23	148	148
FGR	0.02	0.002	-10000	0	-10000	0	0
PTP1B/p130 Cas	-0.02	0.081	0.24	1	-0.26	13	14
Crk/p130 Cas	-0.013	0.083	0.24	1	-0.27	10	11
DOK1	-0.036	0.094	0.2	2	-0.28	21	23
JAK2	-0.14	0.14	0.26	2	-0.33	61	63
Jak2/Leptin Receptor/Leptin	-0.045	0.1	-10000	0	-0.31	13	13
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
PTPN1	-0.027	0.08	0.23	2	-0.26	14	16
LYN	0.02	0.004	-10000	0	-10000	0	0
CDH2	-0.008	0.092	0.29	1	-0.29	27	28
SRC	0.001	0.06	-10000	0	-0.4	4	4
ITGB3	-0.017	0.1	-10000	0	-0.29	34	34
CAT1/PTP1B	-0.001	0.1	0.24	12	-0.29	9	21
CAPN1	0.017	0.01	-10000	0	-10000	0	0
CSK	0.02	0.004	-10000	0	-10000	0	0
PI3K	0.002	0.065	-10000	0	-0.47	1	1
mol:H2O2	0	0.003	-10000	0	-10000	0	0
STAT3 (dimer)	-0.041	0.096	-10000	0	-0.28	12	12
negative regulation of transcription	-0.14	0.14	0.25	2	-0.33	61	63
FCGR2A	0.019	0.006	-10000	0	-10000	0	0
FER	0.016	0.021	-10000	0	-0.3	1	1
alphaIIb/beta3 Integrin	0.001	0.08	0.21	1	-0.21	35	36
BLK	0.064	0.11	0.29	52	-10000	0	52
Insulin Receptor/Insulin/Shc	0.033	0.015	-10000	0	-10000	0	0
RHOA	0.018	0.007	-10000	0	-10000	0	0
LEPR	0.011	0.054	-10000	0	-0.29	9	9
BCAR1	0.02	0.004	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.02	0.005	-10000	0	-10000	0	0
mol:NADPH	-0.001	0.002	-10000	0	-10000	0	0
TRPV6	0.022	0.09	0.26	5	-0.26	4	9
PRL	-0.066	0.12	-10000	0	-0.29	61	61
SOCS3	-0.004	0.19	-10000	0	-1.1	9	9
SPRY2	0.015	0.033	-10000	0	-0.3	3	3
Insulin Receptor/Insulin/IRS1	0.026	0.041	-10000	0	-0.18	10	10
CSF1/CSF1R	-0.013	0.086	-10000	0	-0.26	13	13
Ras protein signal transduction	0.017	0.11	0.55	11	-10000	0	11
IRS1	0.008	0.056	-10000	0	-0.29	10	10
INS	0.004	0.017	-10000	0	-10000	0	0
LEP	0.032	0.08	0.29	24	-10000	0	24
STAT5B	-0.064	0.093	0.26	2	-0.28	21	23
STAT5A	-0.064	0.093	0.26	2	-0.29	19	21
GRB2	0.02	0.005	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.022	0.091	0.21	2	-0.27	21	23
CSN2	-0.06	0.098	-10000	0	-0.47	7	7
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
LAT	0.004	0.053	-10000	0	-0.4	3	3
YBX1	0.022	0.003	-10000	0	-10000	0	0
LCK	0.021	0.001	-10000	0	-10000	0	0
SHC1	0.019	0.006	-10000	0	-10000	0	0
NOX4	0.009	0.049	-10000	0	-0.3	7	7

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.096	0.17	-10000	0	-0.53	10	10
PCK1	-0.026	0.13	0.43	6	-10000	0	6
HNF4A	-0.096	0.18	0.57	1	-0.75	3	4
KCNJ11	-0.1	0.18	-10000	0	-0.58	10	10
AKT1	-0.048	0.13	-10000	0	-0.51	3	3
response to starvation	0.001	0.005	-10000	0	-10000	0	0
DLK1	-0.15	0.28	-10000	0	-0.77	36	36
NKX2-1	-0.15	0.13	-10000	0	-0.38	30	30
ACADM	-0.099	0.16	-10000	0	-0.53	10	10
TAT	-0.039	0.12	0.36	1	-0.5	1	2
CEBPB	0.021	0.01	-10000	0	-10000	0	0
CEBPA	0.023	0.015	-10000	0	-10000	0	0
TTR	0.12	0.14	0.54	17	-10000	0	17
PKLR	-0.093	0.16	-10000	0	-0.54	9	9
APOA1	-0.12	0.22	0.56	1	-0.77	3	4
CPT1C	-0.098	0.17	-10000	0	-0.57	10	10
ALAS1	-0.061	0.12	-10000	0	-0.54	1	1
TFRC	-0.02	0.13	0.44	4	-10000	0	4
FOXF1	0.014	0.04	-10000	0	-0.29	5	5
NF1	0.021	0.004	-10000	0	-10000	0	0
HNF1A (dimer)	0.022	0.023	0.29	2	-10000	0	2
CPT1A	-0.093	0.16	-10000	0	-0.7	1	1
HMGCS1	-0.082	0.16	-10000	0	-0.54	9	9
NR3C1	0.009	0.051	-10000	0	-0.19	18	18
CPT1B	-0.099	0.16	0.41	1	-0.53	10	11
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.02	0.003	-10000	0	-10000	0	0
GCK	-0.13	0.24	-10000	0	-0.7	30	30
CREB1	0.024	0.022	-10000	0	-10000	0	0
IGFBP1	-0.1	0.26	-10000	0	-1	19	19
PDX1	-0.058	0.12	-10000	0	-0.54	1	1
UCP2	-0.094	0.16	-10000	0	-0.53	10	10
ALDOB	-0.1	0.19	0.5	2	-0.57	12	14
AFP	0.11	0.062	0.29	6	-10000	0	6
BDH1	-0.064	0.16	0.41	2	-0.54	8	10
HADH	-0.1	0.18	-10000	0	-0.58	10	10
F2	-0.12	0.21	-10000	0	-0.8	2	2
HNF1A	0.023	0.023	0.29	2	-10000	0	2
G6PC	0.022	0.057	0.35	1	-10000	0	1
SLC2A2	-0.045	0.12	-10000	0	-10000	0	0
INS	-0.006	0.048	0.2	11	-10000	0	11
FOXA1	0.26	0.11	0.31	247	-10000	0	247
FOXA3	0.076	0.1	0.31	43	-10000	0	43
FOXA2	-0.11	0.22	0.5	2	-0.65	12	14
ABCC8	-0.16	0.28	-10000	0	-0.77	41	41
ALB	0.11	0.073	0.3	19	-10000	0	19

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.02	0.002	-10000	0	-10000	0	0
mol:PIP3	-0.02	0.044	-10000	0	-0.19	17	17
FRAP1	0.023	0.074	0.23	1	-0.4	5	6
AKT1	0.022	0.084	0.14	79	-0.2	5	84
INSR	0.02	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.023	0.007	-10000	0	-10000	0	0
mol:GTP	0.024	0.088	0.22	8	-0.18	3	11
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.013	0.02	-10000	0	-0.16	1	1
TSC2	0.02	0.004	-10000	0	-10000	0	0
RHEB/GDP	-0.02	0.032	-10000	0	-0.16	3	3
TSC1	0.021	0.002	-10000	0	-10000	0	0
Insulin Receptor/IRS1	-0.012	0.079	-10000	0	-0.21	39	39
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.005	0.029	-10000	0	-0.17	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.02	0.003	-10000	0	-10000	0	0
RPS6KB1	0.039	0.077	0.25	10	-0.26	1	11
MAP3K5	-0.006	0.034	-10000	0	-0.18	10	10
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
apoptosis	-0.006	0.034	-10000	0	-0.18	10	10
mol:LY294002	0	0	-10000	0	-0.001	38	38
EIF4B	0.034	0.076	0.24	13	-0.24	1	14
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.045	0.067	0.24	7	-0.23	1	8
eIF4E/eIF4G1/eIF4A1	-0.012	0.034	-10000	0	-0.28	3	3
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.001	0.059	-10000	0	-0.2	21	21
mTOR/RHEB/GTP/Raptor/GBL	0.03	0.071	0.21	18	-0.14	3	21
FKBP1A	0.02	0.005	-10000	0	-10000	0	0
RHEB/GTP	0.016	0.076	0.2	2	-10000	0	2
mol:Amino Acids	0	0	-10000	0	-0.001	38	38
FKBP12/Rapamycin	0.016	0.005	-10000	0	-10000	0	0
PDPK1	0.014	0.086	0.15	73	-0.18	16	89
EIF4E	0.02	0.003	-10000	0	-10000	0	0
ASK1/PP5C	0.017	0.12	-10000	0	-0.5	14	14
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	-0.009	0.071	-10000	0	-0.53	2	2
TSC1/TSC2	0.029	0.098	0.25	10	-0.19	3	13
tumor necrosis factor receptor activity	0	0	0.001	38	-10000	0	38
RPS6	0.02	0.004	-10000	0	-10000	0	0
PPP5C	0.02	0.004	-10000	0	-10000	0	0
EIF4G1	0.013	0.01	-10000	0	-10000	0	0
IRS1	-0.024	0.079	-10000	0	-0.22	39	39
INS	-0.016	0.004	-10000	0	-10000	0	0
PTEN	0.017	0.009	-10000	0	-10000	0	0
PDK2	0.014	0.085	0.15	72	-0.18	17	89
EIF4EBP1	-0.032	0.23	-10000	0	-1	14	14
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
PPP2R5D	0.022	0.073	0.26	3	-0.37	5	8
peptide biosynthetic process	-0.018	0.006	-10000	0	-10000	0	0
RHEB	0.02	0.004	-10000	0	-10000	0	0
EIF4A1	0.019	0.006	-10000	0	-10000	0	0
mol:Rapamycin	0.001	0.001	0.003	96	-10000	0	96
EEF2	-0.018	0.006	-10000	0	-10000	0	0
eIF4E/4E-BP1	-0.02	0.21	-10000	0	-0.97	14	14

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.025	0.12	0.54	1	-0.3	33	34
IKBKB	0.01	0.086	0.28	4	-0.29	5	9
AKT1	0.025	0.12	0.24	33	-0.19	15	48
IKBKG	0.018	0.079	0.26	7	-0.28	3	10
CALM1	0.015	0.1	0.32	6	-0.31	3	9
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
MAP3K1	-0.037	0.16	0.4	2	-0.42	39	41
MAP3K7	0.02	0.004	-10000	0	-10000	0	0
mol:Ca2+	0.016	0.099	0.28	8	-0.32	3	11
DOK1	0.02	0.003	-10000	0	-10000	0	0
AP-1	-0.003	0.088	0.26	8	-0.24	4	12
LYN	0.02	0.004	-10000	0	-10000	0	0
BLNK	0.021	0.016	0.29	1	-10000	0	1
SHC1	0.019	0.006	-10000	0	-10000	0	0
BCR complex	0.002	0.078	0.22	2	-0.2	35	37
CD22	-0.052	0.13	-10000	0	-0.4	34	34
CAMK2G	0.011	0.095	0.3	6	-0.31	2	8
CSNK2A1	0.019	0.005	-10000	0	-10000	0	0
INPP5D	0.018	0.007	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.044	0.043	-10000	0	-10000	0	0
GO:0007205	0.015	0.1	0.29	7	-0.32	3	10
SYK	0.02	0.003	-10000	0	-10000	0	0
ELK1	0.014	0.1	0.32	7	-0.31	3	10
NFATC1	-0.027	0.12	0.32	3	-0.32	31	34
B-cell antigen/BCR complex	0.002	0.078	0.22	2	-0.2	35	37
PAG1/CSK	0.028	0.009	-10000	0	-10000	0	0
NFKBIB	0.017	0.041	0.13	7	-0.12	7	14
HRAS	0.008	0.089	0.25	8	-0.26	4	12
NFKBIA	0.017	0.04	0.13	7	-0.12	8	15
NF-kappa-B/RelA/I kappa B beta	0.02	0.036	0.13	7	-10000	0	7
RasGAP/Csk	0.025	0.072	0.21	2	-0.16	33	35
mol:GDP	0.016	0.094	0.28	6	-0.3	3	9
PTEN	0.019	0.005	-10000	0	-10000	0	0
CD79B	-0.017	0.1	-10000	0	-0.29	35	35
NF-kappa-B/RelA/I kappa B alpha	0.02	0.036	0.14	5	-10000	0	5
GRB2	0.02	0.005	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.029	0.17	0.39	2	-0.43	36	38
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
mol:IP3	0.007	0.094	0.28	7	-0.33	3	10
CSK	0.02	0.004	-10000	0	-10000	0	0
FOS	0.002	0.1	0.31	7	-0.3	3	10
CHUK	0.012	0.089	0.29	4	-0.32	6	10
IBTK	0.02	0.004	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	0.024	0.088	0.28	2	-0.28	3	5
PTPN6	-0.054	0.13	-10000	0	-0.39	35	35
RELA	0.02	0.003	-10000	0	-10000	0	0
BCL2A1	0.014	0.027	0.16	2	-10000	0	2
VAV2	-0.041	0.15	-10000	0	-0.42	34	34
ubiquitin-dependent protein catabolic process	0.018	0.04	0.13	7	-0.12	8	15
BTK	0.019	0.012	-10000	0	-10000	0	0
CD19	-0.053	0.13	-10000	0	-0.4	35	35
MAP4K1	0.019	0.005	-10000	0	-10000	0	0
CD72	0.02	0.003	-10000	0	-10000	0	0
PAG1	0.02	0.005	-10000	0	-10000	0	0
MAPK14	-0.032	0.15	0.46	2	-0.36	38	40
SH3BP5	-0.005	0.084	-10000	0	-0.29	23	23
PIK3AP1	-0.003	0.1	0.23	5	-0.33	5	10
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	0.003	0.064	-10000	0	-0.37	3	3
RAF1	0.003	0.085	0.24	7	-0.26	3	10
RasGAP/p62DOK/SHIP	0.022	0.071	-10000	0	-0.16	31	31
CD79A	0.022	0.023	0.29	2	-10000	0	2
re-entry into mitotic cell cycle	-0.003	0.087	0.26	8	-0.23	5	13
RASA1	0.02	0.004	-10000	0	-10000	0	0
MAPK3	-0.003	0.08	0.27	5	-0.24	2	7
MAPK1	-0.003	0.079	0.24	5	-0.24	2	7
CD72/SHP1	-0.035	0.14	0.26	11	-0.38	33	44
NFKB1	0.02	0.003	-10000	0	-10000	0	0
MAPK8	-0.036	0.14	0.37	2	-0.36	38	40
actin cytoskeleton organization	-0.036	0.14	0.3	4	-0.38	33	37
NF-kappa-B/RelA	0.04	0.071	0.24	7	-0.2	3	10
Calcineurin	0.026	0.087	0.33	2	-0.29	2	4
PI3K	-0.05	0.092	-10000	0	-0.3	31	31
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.002	0.1	0.25	5	-0.3	9	14
SOS1	0.02	0.003	-10000	0	-10000	0	0
Bam32/HPK1	-0.04	0.21	-10000	0	-0.54	40	40
DAPP1	-0.06	0.22	-10000	0	-0.6	38	38
cytokine secretion	-0.024	0.11	0.32	3	-0.31	30	33
mol:DAG	0.007	0.094	0.28	7	-0.33	3	10
PLCG2	0.02	0.004	-10000	0	-10000	0	0
MAP2K1	0	0.083	0.23	7	-0.25	3	10
B-cell antigen/BCR complex/FcgammaRIIB	0.011	0.073	0.21	2	-0.18	35	37
mol:PI-3-4-5-P3	-0.01	0.097	0.19	12	-0.25	19	31
ETS1	0.005	0.089	0.28	7	-0.29	2	9
B-cell antigen/BCR complex/LYN/SYK/BLNK	0.03	0.071	-10000	0	-0.16	28	28
B-cell antigen/BCR complex/LYN	-0.037	0.14	-10000	0	-0.41	35	35
MALT1	0.02	0.005	-10000	0	-10000	0	0
TRAF6	0.02	0.004	-10000	0	-10000	0	0
RAC1	-0.041	0.14	0.24	3	-0.4	33	36
B-cell antigen/BCR complex/LYN/SYK	-0.015	0.14	-10000	0	-0.38	33	33
CARD11	0.013	0.1	0.31	6	-0.31	3	9
FCGR2B	0.017	0.026	-10000	0	-0.29	2	2
PPP3CA	0.02	0.003	-10000	0	-10000	0	0
BCL10	0.021	0.002	-10000	0	-10000	0	0
IKK complex	0.015	0.051	0.17	10	-0.13	1	11
PTPRC	0.018	0.019	-10000	0	-0.29	1	1
PDPK1	0.005	0.095	0.21	26	-0.18	17	43
PPP3CB	0.02	0.003	-10000	0	-10000	0	0
PPP3CC	0.019	0.006	-10000	0	-10000	0	0
POU2F2	0.013	0.029	0.17	3	-10000	0	3

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	-0.011	0.064	0.21	20	-0.21	3	23
KIRREL	0.018	0.013	-10000	0	-10000	0	0
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.011	0.064	0.21	3	-0.21	20	23
PLCG1	0.019	0.005	-10000	0	-10000	0	0
ARRB2	0.019	0.006	-10000	0	-10000	0	0
WASL	0.02	0.005	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	0.029	0.056	0.2	3	-0.16	18	21
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.004	0.047	-10000	0	-0.19	15	15
FYN	-0.002	0.084	0.21	30	-0.16	16	46
mol:Ca2+	0.029	0.052	0.2	2	-0.16	16	18
mol:DAG	0.029	0.053	0.2	2	-0.16	16	18
NPHS2	-0.015	0.019	-10000	0	-10000	0	0
mol:IP3	0.029	0.053	0.2	2	-0.16	16	18
regulation of endocytosis	0.019	0.053	0.18	3	-0.15	17	20
Nephrin/NEPH1/podocin/Cholesterol	0.019	0.052	0.19	3	-0.15	20	23
establishment of cell polarity	0.011	0.064	0.21	3	-0.21	20	23
Nephrin/NEPH1/podocin/NCK1-2	0.029	0.054	-10000	0	-0.15	14	14
Nephrin/NEPH1/beta Arrestin2	0.021	0.055	0.19	3	-0.15	17	20
NPHS1	0.007	0.05	0.3	6	-10000	0	6
Nephrin/NEPH1/podocin	0.018	0.053	0.19	3	-0.14	25	28
TJP1	0.02	0.004	-10000	0	-10000	0	0
NCK1	0.015	0.009	-10000	0	-10000	0	0
NCK2	0.02	0.002	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.03	0.053	0.2	2	-0.16	16	18
CD2AP	0.02	0.004	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	0.029	0.057	0.2	3	-0.16	18	21
GRB2	0.02	0.005	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.006	0.077	0.21	24	-0.15	16	40
cytoskeleton organization	-0.016	0.054	0.18	8	-0.2	14	22
Nephrin/NEPH1	0.012	0.045	0.18	3	-0.14	20	23
Nephrin/NEPH1/ZO-1	0.021	0.057	0.2	3	-0.17	18	21

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.021	0.001	-10000	0	-10000	0	0
HDAC2	0.02	0.003	-10000	0	-10000	0	0
GNB1/GNG2	0.023	0.054	-10000	0	-0.17	19	19
forebrain development	-0.13	0.22	-10000	0	-0.48	64	64
GNAO1	0.012	0.034	-10000	0	-0.29	3	3
SMO/beta Arrestin2	0.006	0.058	-10000	0	-0.2	19	19
SMO	-0.005	0.077	-10000	0	-0.29	19	19
ARRB2	0.015	0.013	-10000	0	-10000	0	0
GLI3/SPOP	0.01	0.1	-10000	0	-0.32	8	8
mol:GTP	0	0.002	-10000	0	-10000	0	0
GSK3B	0.017	0.008	-10000	0	-10000	0	0
GNAI2	0.015	0.013	-10000	0	-10000	0	0
SIN3/HDAC complex	0.047	0.019	-10000	0	-10000	0	0
GNAI1	0.014	0.022	-10000	0	-0.29	1	1
XPO1	0.015	0.016	-10000	0	-10000	0	0
GLI1/Su(fu)	-0.12	0.22	-10000	0	-0.56	44	44
SAP30	0.02	0.005	-10000	0	-10000	0	0
mol:GDP	-0.005	0.076	-10000	0	-0.29	19	19
MIM/GLI2A	0.005	0.043	-10000	0	-0.12	23	23
IFT88	0.02	0.004	-10000	0	-10000	0	0
GNAI3	0.016	0.013	-10000	0	-10000	0	0
GLI2	-0.015	0.087	0.2	3	-0.29	10	13
GLI3	0.002	0.1	0.21	3	-0.33	8	11
CSNK1D	0.02	0.004	-10000	0	-10000	0	0
CSNK1E	0.02	0.003	-10000	0	-10000	0	0
SAP18	0.02	0.004	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.02	0.004	-10000	0	-10000	0	0
GNG2	0.02	0.003	-10000	0	-10000	0	0
Gi family/GTP	-0.053	0.1	-10000	0	-0.24	45	45
SIN3B	0.02	0.003	-10000	0	-10000	0	0
SIN3A	0.02	0.004	-10000	0	-10000	0	0
GLI3/Su(fu)	-0.002	0.098	-10000	0	-0.34	13	13
GLI2/Su(fu)	-0.026	0.098	0.21	1	-0.31	15	16
FOXA2	-0.12	0.31	-10000	0	-0.88	41	41
neural tube patterning	-0.13	0.22	-10000	0	-0.48	64	64
SPOP	0.02	0.003	-10000	0	-10000	0	0
Su(fu)/PIAS1	-0.013	0.063	-10000	0	-0.18	1	1
GNB1	0.02	0.004	-10000	0	-10000	0	0
CSNK1G2	0.019	0.005	-10000	0	-10000	0	0
CSNK1G3	0.02	0.004	-10000	0	-10000	0	0
MTSS1	0.005	0.043	-10000	0	-0.12	23	23
embryonic limb morphogenesis	-0.13	0.22	-10000	0	-0.48	64	64
SUFU	-0.002	0.035	-10000	0	-10000	0	0
LGALS3	0.02	0.003	-10000	0	-10000	0	0
catabolic process	-0.016	0.12	0.28	1	-0.37	11	12
GLI3A/CBP	-0.03	0.11	-10000	0	-0.29	44	44
KIF3A	0.02	0.005	-10000	0	-10000	0	0
GLI1	-0.13	0.22	-10000	0	-0.5	64	64
RAB23	0.02	0.004	-10000	0	-10000	0	0
CSNK1A1	0.02	0.004	-10000	0	-10000	0	0
IFT172	0.02	0.004	-10000	0	-10000	0	0
RBBP7	0.02	0.004	-10000	0	-10000	0	0
Su(fu)/Galectin3	-0.014	0.064	-10000	0	-0.18	1	1
GNAZ	-0.053	0.13	-10000	0	-0.29	66	66
RBBP4	0.021	0.001	-10000	0	-10000	0	0
CSNK1G1	0.02	0.003	-10000	0	-10000	0	0
PIAS1	0.02	0.003	-10000	0	-10000	0	0
PRKACA	0.02	0.004	-10000	0	-10000	0	0
GLI2/SPOP	-0.009	0.087	0.22	1	-0.28	10	11
STK36	0.014	0.016	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.055	0.096	-10000	0	-0.29	23	23
PTCH1	-0.12	0.21	-10000	0	-0.59	33	33
MIM/GLI1	-0.14	0.24	-10000	0	-0.48	81	81
CREBBP	-0.03	0.11	-10000	0	-0.29	44	44
Su(fu)/SIN3/HDAC complex	-0.004	0.048	-10000	0	-0.27	3	3

×

Presenilin action in Notch and Wnt signaling

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
Delta 1/NOTCH/NOTCH(cleaved)	0.019	0.075	-10000	0	-0.39	9	9
HDAC1	0.02	0.004	-10000	0	-10000	0	0
AES	0.02	0.005	-10000	0	-10000	0	0
FBXW11	0.02	0.004	-10000	0	-10000	0	0
DTX1	0.021	0.002	-10000	0	-10000	0	0
LRP6/FZD1	0.028	0.009	-10000	0	-10000	0	0
TLE1	0.02	0.003	-10000	0	-10000	0	0
AP1	-0.008	0.056	-10000	0	-0.19	22	22
NCSTN	0.019	0.005	-10000	0	-10000	0	0
ADAM10	0.02	0.004	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.003	0.09	-10000	0	-0.62	5	5
NICD/RBPSUH	0.02	0.08	-10000	0	-0.39	10	10
WIF1	-0.045	0.12	0.29	3	-0.29	51	54
NOTCH1	0	0.077	-10000	0	-0.41	10	10
PSENEN	0.02	0.005	-10000	0	-10000	0	0
KREMEN2	0.18	0.14	0.29	168	-10000	0	168
DKK1	0.005	0.077	0.29	3	-0.29	16	19
beta catenin/beta TrCP1	0.001	0.072	-10000	0	-0.29	5	5
APH1B	0.02	0.003	-10000	0	-10000	0	0
APH1A	0.019	0.005	-10000	0	-10000	0	0
AXIN1	0.009	0.058	-10000	0	-0.36	4	4
CtBP/CBP/TCF1/TLE1/AES	0	0.04	-10000	0	-10000	0	0
PSEN1	0.02	0.003	-10000	0	-10000	0	0
FOS	-0.003	0.082	-10000	0	-0.29	22	22
JUN	0.019	0.018	-10000	0	-0.29	1	1
MAP3K7	0.02	0.004	-10000	0	-10000	0	0
CTNNB1	-0.009	0.073	-10000	0	-0.3	5	5
MAPK3	0.02	0.002	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.12	0.093	0.21	150	-0.12	5	155
HNF1A	0.022	0.023	0.29	2	-10000	0	2
CTBP1	0.019	0.006	-10000	0	-10000	0	0
MYC	-0.003	0.14	-10000	0	-1	5	5
NKD1	0.019	0.042	0.29	3	-0.29	3	6
FZD1	0.02	0.004	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	0.022	0.082	-10000	0	-0.39	10	10
apoptosis	-0.008	0.055	-10000	0	-0.19	22	22
Delta 1/NOTCHprecursor	0.021	0.078	-10000	0	-0.39	9	9
DLL1	0.019	0.005	-10000	0	-10000	0	0
PPARD	0.005	0.095	-10000	0	-0.79	4	4
Gamma Secretase	0.051	0.024	-10000	0	-10000	0	0
APC	-0.003	0.089	-10000	0	-0.39	11	11
DVL1	-0.005	0.037	-10000	0	-0.24	6	6
CSNK2A1	0.019	0.007	-10000	0	-10000	0	0
MAP3K7IP1	0	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	0.11	0.11	0.21	151	-0.15	15	166
LRP6	0.02	0.005	-10000	0	-10000	0	0
CSNK1A1	0.019	0.006	-10000	0	-10000	0	0
NLK	0.006	0.005	-10000	0	-10000	0	0
CCND1	-0.009	0.14	-10000	0	-0.79	9	9
WNT1	0.017	0.02	0.29	1	-10000	0	1
Axin1/APC/beta catenin	-0.002	0.094	0.25	3	-0.32	11	14
DKK2	0.014	0.044	0.29	1	-0.29	5	6
NOTCH1 precursor/DVL1	-0.009	0.096	-10000	0	-0.41	12	12
GSK3B	0.017	0.008	-10000	0	-10000	0	0
FRAT1	0.02	0.003	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	0.02	0.079	-10000	0	-0.39	10	10
PPP2R5D	0.003	0.054	-10000	0	-0.3	7	7
MAPK1	0.02	0.002	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.013	0.083	0.21	4	-0.16	51	55
RBPJ	0.019	0.006	-10000	0	-10000	0	0
CREBBP	0.02	0.005	-10000	0	-10000	0	0

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.02	0.005	-10000	0	-10000	0	0
EGFR	0.018	0.026	-10000	0	-0.29	2	2
EGF/EGFR	0.004	0.071	-10000	0	-0.15	50	50
EGF/EGFR dimer/SHC/GRB2/SOS1	0.04	0.053	-10000	0	-0.16	15	15
mol:GTP	0	0	-10000	0	-10000	0	0
EDNRA	-0.024	0.11	-10000	0	-0.29	41	41
response to oxidative stress	0	0	-10000	0	-10000	0	0
EGF	0.003	0.066	-10000	0	-0.29	14	14
EGF/EGFR dimer/SHC	0.026	0.049	-10000	0	-0.17	15	15
mol:GDP	0.034	0.05	-10000	0	-0.16	15	15
mol:Ca2+	0	0	-10000	0	-10000	0	0
EDN1	0.018	0.019	-10000	0	-0.29	1	1
GRB2/SOS1	0.028	0.008	-10000	0	-10000	0	0
HRAS/GTP	0.02	0.044	-10000	0	-0.15	15	15
SHC1	0.019	0.006	-10000	0	-10000	0	0
HRAS/GDP	0.031	0.049	-10000	0	-0.15	15	15
FRAP1	-0.028	0.033	0.15	2	-0.15	15	17
EGF/EGFR dimer	0.017	0.052	-10000	0	-0.2	15	15
SOS1	0.02	0.003	-10000	0	-10000	0	0
GRB2	0.02	0.005	-10000	0	-10000	0	0
ETA receptor/Endothelin-1	-0.005	0.081	-10000	0	-0.2	42	42

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.036	0.091	-10000	0	-0.16	91	91
TC10/GTP	-0.031	0.083	-10000	0	-0.14	99	99
Insulin Receptor/Insulin/IRS1/Shp2	0.039	0.045	-10000	0	-0.16	10	10
HRAS	0.02	0.005	-10000	0	-10000	0	0
APS homodimer	0.02	0.004	-10000	0	-10000	0	0
GRB14	0.07	0.11	0.29	54	-10000	0	54
FOXO3	0.016	0.097	-10000	0	-0.63	6	6
AKT1	0.039	0.094	0.2	36	-10000	0	36
INSR	0.022	0.009	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.038	0.03	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.019	0.018	-10000	0	-0.29	1	1
SORBS1	-0.096	0.15	-10000	0	-0.29	109	109
CRK	0.019	0.006	-10000	0	-10000	0	0
PTPN1	-0.015	0.017	0.15	3	-10000	0	3
CAV1	-0.03	0.048	-10000	0	-0.17	26	26
CBL/APS/CAP/Crk-II/C3G	-0.025	0.097	-10000	0	-0.15	104	104
Insulin Receptor/Insulin/IRS1/NCK2	0.039	0.045	-10000	0	-0.16	10	10
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.02	0.032	-10000	0	-0.15	5	5
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	-0.001	0.079	-10000	0	-0.32	12	12
RPS6KB1	0.029	0.087	0.18	37	-10000	0	37
PARD6A	0.02	0.004	-10000	0	-10000	0	0
CBL	0.017	0.008	-10000	0	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.015	0.007	-10000	0	-10000	0	0
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	0.017	0.072	0.15	15	-10000	0	15
HRAS/GTP	-0.03	0.027	-10000	0	-0.15	6	6
Insulin Receptor	0.022	0.009	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.041	0.046	-10000	0	-0.16	7	7
PRKCI	0.005	0.053	-10000	0	-0.3	8	8
Insulin Receptor/Insulin/GRB14/PDK1	-0.007	0.041	0.1	4	-0.15	3	7
SHC1	0.019	0.006	-10000	0	-10000	0	0
negative regulation of MAPKKK cascade	0.028	0.02	-10000	0	-10000	0	0
PI3K	0.025	0.036	-10000	0	-0.15	5	5
NCK2	0.02	0.002	-10000	0	-10000	0	0
RHOQ	0.02	0.004	-10000	0	-10000	0	0
mol:H2O2	-0.003	0.003	-10000	0	-10000	0	0
HRAS/GDP	0.015	0.003	-10000	0	-10000	0	0
AKT2	0.036	0.092	0.2	32	-10000	0	32
PRKCZ	-0.002	0.072	-10000	0	-0.3	15	15
SH2B2	0.02	0.004	-10000	0	-10000	0	0
SHC/SHIP	-0.021	0.031	-10000	0	-10000	0	0
F2RL2	0.002	0.073	-10000	0	-0.29	17	17
TRIP10	0.02	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insulin/Shc	0.035	0.018	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.026	0.007	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.049	0.03	-10000	0	-10000	0	0
RAPGEF1	0.02	0.002	-10000	0	-10000	0	0
RASA1	0.02	0.004	-10000	0	-10000	0	0
NCK1	0.015	0.009	-10000	0	-10000	0	0
CBL/APS/CAP/Crk-II	-0.031	0.097	-10000	0	-0.16	106	106
TC10/GDP	0.015	0.003	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.045	0.026	-10000	0	-0.17	1	1
INPP5D	-0.021	0.03	-10000	0	-0.15	9	9
SOS1	0.02	0.003	-10000	0	-10000	0	0
SGK1	-0.01	0.1	-10000	0	-0.61	8	8
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.021	0.001	-10000	0	-10000	0	0
IRS1	0.008	0.056	-10000	0	-0.29	10	10
p62DOK/RasGAP	0.028	0.021	-10000	0	-10000	0	0
INS	-0.014	0.017	-10000	0	-10000	0	0
mol:PI-3-4-P2	-0.021	0.03	-10000	0	-0.15	9	9
GRB2	0.02	0.005	-10000	0	-10000	0	0
EIF4EBP1	0.028	0.087	0.18	40	-10000	0	40
PTPRA	0.02	0.006	-10000	0	-10000	0	0
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
TC10/GTP/CIP4	0.026	0.007	-10000	0	-10000	0	0
PDPK1	0.02	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0	0.042	-10000	0	-0.18	10	10
Insulin Receptor/Insulin/IRS1	0.029	0.04	-10000	0	-0.16	10	10
Insulin Receptor/Insulin/IRS3	0.029	0.017	-10000	0	-10000	0	0
Par3/Par6	0.032	0.047	-10000	0	-0.15	16	16

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.014	0.099	0.2	1	-0.33	22	23
PDGFB-D/PDGFRB/SLAP	0.017	0.048	-10000	0	-0.2	13	13
PDGFB-D/PDGFRB/APS/CBL	0.024	0.047	-10000	0	-0.16	15	15
AKT1	0.041	0.11	0.32	19	-10000	0	19
mol:PI-4-5-P2	0	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	-0.001	0.12	0.22	4	-0.36	22	26
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
FGR	-0.013	0.072	-10000	0	-0.36	4	4
mol:Ca2+	-0.009	0.13	0.21	15	-0.38	22	37
MYC	0	0.13	0.32	4	-0.66	5	9
SHC1	0.019	0.006	-10000	0	-10000	0	0
HRAS/GDP	-0.014	0.059	0.16	24	-0.16	1	25
LRP1/PDGFRB/PDGFB	0.029	0.048	-10000	0	-0.17	15	15
GRB10	0.019	0.018	-10000	0	-0.29	1	1
PTPN11	0.021	0.001	-10000	0	-10000	0	0
GO:0007205	-0.009	0.13	0.22	14	-0.39	22	36
PTEN	0.019	0.005	-10000	0	-10000	0	0
GRB2	0.02	0.005	-10000	0	-10000	0	0
GRB7	0.021	0.023	0.29	2	-10000	0	2
PDGFB-D/PDGFRB/SHP2	0.017	0.054	-10000	0	-0.2	16	16
PDGFB-D/PDGFRB/GRB10	0.017	0.055	-10000	0	-0.21	15	15
cell cycle arrest	0.017	0.048	-10000	0	-0.2	13	13
HRAS	0.02	0.005	-10000	0	-10000	0	0
HIF1A	0.033	0.1	0.27	23	-10000	0	23
GAB1	-0.008	0.12	0.27	1	-0.39	18	19
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	-0.007	0.12	0.21	13	-0.36	17	30
PDGFB-D/PDGFRB	0.026	0.049	-10000	0	-0.18	14	14
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.017	0.052	-10000	0	-0.2	15	15
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.01	0.091	-10000	0	-0.32	18	18
positive regulation of MAPKKK cascade	0.017	0.053	-10000	0	-0.2	16	16
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
mol:IP3	-0.009	0.13	0.22	14	-0.39	22	36
E5	0	0.001	-10000	0	-10000	0	0
CSK	0.016	0.013	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7	0.017	0.055	0.22	2	-0.2	15	17
SHB	0.02	0.003	-10000	0	-10000	0	0
BLK	-0.021	0.16	0.32	4	-0.44	27	31
PTPN2	0.017	0.013	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.017	0.054	-10000	0	-0.2	16	16
BCAR1	0.02	0.004	-10000	0	-10000	0	0
VAV2	-0.007	0.13	0.24	6	-0.39	19	25
CBL	0.017	0.008	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.016	0.053	-10000	0	-0.2	16	16
LCK	-0.009	0.06	-10000	0	-10000	0	0
PDGFRB	0.003	0.07	-10000	0	-0.3	15	15
ACP1	0.02	0.004	-10000	0	-10000	0	0
HCK	-0.011	0.057	-10000	0	-10000	0	0
ABL1	-0.001	0.11	0.21	16	-0.32	18	34
PDGFB-D/PDGFRB/CBL	-0.018	0.14	0.25	1	-0.44	23	24
PTPN1	0.015	0.014	-10000	0	-10000	0	0
SNX15	0.02	0.003	-10000	0	-10000	0	0
STAT3	0.02	0.002	-10000	0	-10000	0	0
STAT1	0.02	0.004	-10000	0	-10000	0	0
cell proliferation	0.002	0.12	0.31	4	-0.58	5	9
SLA	0.019	0.005	-10000	0	-10000	0	0
actin cytoskeleton reorganization	0.02	0.1	0.19	55	-10000	0	55
SRC	-0.012	0.062	-10000	0	-0.38	1	1
PI3K	-0.022	0.028	-10000	0	-0.16	5	5
PDGFB-D/PDGFRB/GRB7/SHC	0.026	0.05	0.21	2	-0.17	14	16
SH2B2	0.02	0.004	-10000	0	-10000	0	0
PLCgamma1/SPHK1	-0.002	0.12	0.23	4	-0.37	22	26
LYN	-0.013	0.073	-10000	0	-0.78	1	1
LRP1	0.02	0.002	-10000	0	-10000	0	0
SOS1	0.02	0.003	-10000	0	-10000	0	0
STAT5B	0.02	0.002	-10000	0	-10000	0	0
STAT5A	0.02	0.002	-10000	0	-10000	0	0
NCK1-2/p130 Cas	0.034	0.043	-10000	0	-0.16	6	6
SPHK1	0.017	0.012	-10000	0	-10000	0	0
EDG1	0	0.003	-10000	0	-10000	0	0
mol:DAG	-0.009	0.13	0.22	14	-0.39	22	36
PLCG1	-0.01	0.13	0.23	5	-0.4	22	27
NHERF/PDGFRB	0.035	0.061	0.21	13	-0.17	15	28
YES1	-0.02	0.09	-10000	0	-0.42	8	8
cell migration	0.034	0.061	0.21	13	-0.17	15	28
SHC/Grb2/SOS1	0.037	0.051	-10000	0	-0.16	12	12
SLC9A3R2	0.02	0.004	-10000	0	-10000	0	0
SLC9A3R1	0.033	0.059	0.29	14	-10000	0	14
NHERF1-2/PDGFRB/PTEN	0.041	0.061	0.21	13	-0.16	15	28
FYN	-0.031	0.14	-10000	0	-0.59	13	13
DOK1	-0.018	0.055	0.16	17	-0.17	14	31
HRAS/GTP	0.015	0.003	-10000	0	-10000	0	0
PDGFB	0.02	0.002	-10000	0	-10000	0	0
RAC1	-0.01	0.13	0.27	1	-0.42	16	17
PRKCD	-0.012	0.061	0.17	23	-0.17	11	34
FER	-0.014	0.063	0.17	24	-0.17	14	38
MAPKKK cascade	0.001	0.088	0.2	22	-10000	0	22
RASA1	-0.014	0.063	0.17	24	-0.17	14	38
NCK1	0.015	0.009	-10000	0	-10000	0	0
NCK2	0.02	0.002	-10000	0	-10000	0	0
p62DOK/Csk	-0.018	0.058	0.16	23	-0.16	13	36
PDGFB-D/PDGFRB/SHB	0.016	0.054	-10000	0	-0.2	16	16
chemotaxis	-0.001	0.11	0.21	16	-0.31	18	34
STAT1-3-5/STAT1-3-5	0.03	0.049	-10000	0	-0.16	14	14
Bovine Papilomavirus E5/PDGFRB	0.002	0.049	-10000	0	-0.2	16	16
PTPRJ	0.02	0.004	-10000	0	-10000	0	0

×

ErbB2/ErbB3 signaling events

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
USP8	-0.013	0.007	-10000	0	-10000	0	0
RAS family/GTP	0.044	0.06	0.22	2	-10000	0	2
NFATC4	-0.016	0.068	0.19	13	-0.17	3	16
ERBB2IP	0.016	0.012	-10000	0	-10000	0	0
HSP90 (dimer)	0.02	0.004	-10000	0	-10000	0	0
mammary gland morphogenesis	0.014	0.088	0.18	56	-10000	0	56
JUN	0.015	0.06	0.24	5	-10000	0	5
HRAS	0.019	0.006	-10000	0	-10000	0	0
DOCK7	0	0.072	0.21	17	-10000	0	17
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.066	0.083	0.22	61	-10000	0	61
AKT1	-0.008	0.006	-10000	0	-10000	0	0
BAD	-0.014	0.004	-10000	0	-10000	0	0
MAPK10	-0.025	0.058	0.15	9	-0.14	6	15
mol:GTP	0	0.001	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	0.015	0.094	0.19	56	-10000	0	56
RAF1	0.008	0.066	0.23	7	-10000	0	7
ErbB2/ErbB3/neuregulin 2	-0.018	0.073	0.22	14	-0.17	27	41
STAT3	0.018	0.073	-10000	0	-0.85	2	2
cell migration	-0.031	0.061	0.19	6	-0.17	5	11
mol:PI-3-4-5-P3	0	0.001	-10000	0	-10000	0	0
cell proliferation	-0.007	0.14	0.4	1	-0.48	4	5
FOS	-0.013	0.14	0.35	3	-0.42	23	26
NRAS	0.02	0.004	-10000	0	-10000	0	0
mol:Ca2+	0.014	0.088	0.18	56	-10000	0	56
MAPK3	-0.001	0.12	0.35	1	-0.46	6	7
MAPK1	-0.002	0.12	0.35	1	-0.46	7	8
JAK2	0.001	0.071	0.21	16	-10000	0	16
NF2	0	0.053	-10000	0	-0.64	2	2
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0.031	0.061	0.18	24	-10000	0	24
NRG1	0.064	0.1	0.3	50	-10000	0	50
GRB2/SOS1	0.028	0.008	-10000	0	-10000	0	0
MAPK8	0.008	0.081	0.23	12	-0.24	2	14
MAPK9	-0.012	0.043	0.17	6	-10000	0	6
ERBB2	-0.014	0.04	0.26	6	-10000	0	6
ERBB3	0.029	0.053	0.29	11	-10000	0	11
SHC1	0.019	0.006	-10000	0	-10000	0	0
RAC1	0.02	0.003	-10000	0	-10000	0	0
apoptosis	0.01	0.007	-10000	0	-10000	0	0
STAT3 (dimer)	0.018	0.072	-10000	0	-0.84	2	2
RNF41	-0.016	0.008	-10000	0	-10000	0	0
FRAP1	-0.007	0.003	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.022	0.029	-10000	0	-10000	0	0
ErbB2/ErbB2/HSP90 (dimer)	-0.017	0.03	0.19	5	-10000	0	5
CHRNA1	0.006	0.1	0.33	5	-0.33	3	8
myelination	-0.012	0.074	0.24	11	-10000	0	11
PPP3CB	-0.001	0.068	0.2	16	-10000	0	16
KRAS	0.019	0.005	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0.048	0.06	0.22	2	-10000	0	2
NRG2	-0.014	0.094	-10000	0	-0.29	30	30
mol:GDP	0.031	0.061	0.18	24	-10000	0	24
SOS1	0.02	0.003	-10000	0	-10000	0	0
MAP2K2	0.003	0.065	0.22	6	-10000	0	6
SRC	0.019	0.006	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.001	-10000	0	-10000	0	0
PTPN11	0.001	0.072	0.21	17	-10000	0	17
MAP2K1	-0.002	0.15	0.38	1	-0.52	11	12
heart morphogenesis	0.014	0.088	0.18	56	-10000	0	56
RAS family/GDP	0.05	0.063	0.22	3	-10000	0	3
GRB2	0.02	0.005	-10000	0	-10000	0	0
PRKACA	0.006	0.056	-10000	0	-0.67	2	2
CHRNE	0.006	0.015	0.12	1	-10000	0	1
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
activation of caspase activity	0.008	0.006	-10000	0	-10000	0	0
nervous system development	0.014	0.088	0.18	56	-10000	0	56
CDC42	0.02	0.003	-10000	0	-10000	0	0

×

Noncanonical Wnt 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
NFATC2	0.008	0.054	-10000	0	-0.29	9	9
GNB1/GNG2	-0.011	0.09	-10000	0	-0.26	12	12
mol:DAG	-0.042	0.068	0.17	1	-0.24	11	12
PLCG1	-0.043	0.07	0.17	1	-0.24	11	12
YES1	-0.036	0.067	-10000	0	-0.2	30	30
FZD3	0.009	0.054	-10000	0	-0.29	9	9
FZD6	0.019	0.005	-10000	0	-10000	0	0
G protein	-0.009	0.093	0.24	1	-0.24	11	12
MAP3K7	-0.067	0.085	0.18	2	-0.25	27	29
mol:Ca2+	-0.041	0.067	0.16	1	-0.23	11	12
mol:IP3	-0.042	0.068	0.17	1	-0.24	11	12
NLK	-0.003	0.081	-10000	0	-0.8	3	3
GNB1	0.02	0.004	-10000	0	-10000	0	0
CAMK2A	-0.068	0.091	0.19	2	-0.25	32	34
MAP3K7IP1	0	0	-10000	0	-10000	0	0
Noncanonical Wnts/FZD	-0.025	0.077	-10000	0	-0.21	33	33
CSNK1A1	0.02	0.004	-10000	0	-10000	0	0
GNAS	-0.035	0.065	-10000	0	-0.19	32	32
GO:0007205	-0.039	0.068	0.16	1	-0.23	12	13
WNT6	0.011	0.048	-10000	0	-0.29	7	7
WNT4	0.016	0.036	-10000	0	-0.29	4	4
NFAT1/CK1 alpha	-0.02	0.086	0.24	1	-0.27	8	9
GNG2	0.02	0.003	-10000	0	-10000	0	0
WNT5A	0.019	0.006	-10000	0	-10000	0	0
WNT11	0.012	0.053	0.29	1	-0.29	8	9
CDC42	-0.036	0.066	-10000	0	-0.29	7	7

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.019	0.044	-10000	0	-10000	0	0
epithelial cell differentiation	-0.087	0.096	-10000	0	-0.34	6	6
ITCH	0.019	0.017	-10000	0	-10000	0	0
WWP1	0.006	0.032	-10000	0	-10000	0	0
FYN	0.015	0.04	-10000	0	-0.29	5	5
EGFR	0.018	0.026	-10000	0	-0.29	2	2
PRL	-0.068	0.12	-10000	0	-0.29	61	61
neuron projection morphogenesis	0.005	0.07	0.28	3	-10000	0	3
PTPRZ1	0.14	0.14	0.29	135	-10000	0	135
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.037	0.058	-10000	0	-10000	0	0
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	0.017	0.054	0.26	2	-10000	0	2
ADAM17	0.017	0.019	-10000	0	-10000	0	0
ErbB4/ErbB4	0.009	0.021	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	0.019	0.047	-10000	0	-10000	0	0
NCOR1	0.019	0.006	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	0.029	0.051	0.24	1	-10000	0	1
GRIN2B	0.005	0.052	0.25	3	-10000	0	3
ErbB4/ErbB2/betacellulin	0.019	0.04	-10000	0	-10000	0	0
STAT1	0.02	0.004	-10000	0	-10000	0	0
HBEGF	0.02	0.004	-10000	0	-10000	0	0
PRLR	-0.11	0.15	-10000	0	-0.29	123	123
E4ICDs/ETO2	0.016	0.044	-10000	0	-10000	0	0
axon guidance	-0.025	0.064	-10000	0	-10000	0	0
NEDD4	0.015	0.019	-10000	0	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	-0.11	0.13	-10000	0	-0.23	148	148
CBFA2T3	0.014	0.04	-10000	0	-0.29	5	5
ErbB4/ErbB2/HBEGF	0.02	0.04	-10000	0	-10000	0	0
MAPK3	0.008	0.068	0.29	2	-10000	0	2
STAT1 (dimer)	0.02	0.043	-10000	0	-10000	0	0
MAPK1	0.009	0.068	0.29	2	-10000	0	2
JAK2	0.019	0.005	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	0.011	0.054	0.23	3	-10000	0	3
NRG1	0.015	0.068	0.16	51	-10000	0	51
NRG3	0	0.035	0.29	3	-10000	0	3
NRG2	-0.014	0.094	-10000	0	-0.29	30	30
NRG4	0.042	0.076	0.29	24	-10000	0	24
heart development	-0.025	0.064	-10000	0	-10000	0	0
neural crest cell migration	0.011	0.053	0.23	3	-10000	0	3
ERBB2	-0.008	0.046	0.27	7	-10000	0	7
WWOX/E4ICDs	0.018	0.042	-10000	0	-10000	0	0
SHC1	0.019	0.006	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	0.041	0.064	0.33	1	-10000	0	1
apoptosis	-0.027	0.048	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	0.014	0.045	-10000	0	-10000	0	0
ErbB4/ErbB2/epiregulin	0.061	0.085	0.3	6	-10000	0	6
ErbB4/ErbB4/betacellulin/betacellulin	0.018	0.043	-10000	0	-10000	0	0
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.063	0.1	-10000	0	-0.31	5	5
MDM2	0.006	0.033	-10000	0	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	0.026	0.04	-10000	0	-10000	0	0
STAT5A	-0.029	0.063	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	0.03	0.051	0.24	1	-10000	0	1
DLG4	0.009	0.054	-10000	0	-0.29	9	9
GRB2/SHC	0.027	0.01	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	0.015	0.04	-10000	0	-10000	0	0
STAT5A (dimer)	-0.09	0.1	-10000	0	-0.39	4	4
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.019	0.072	-10000	0	-10000	0	0
LRIG1	0.019	0.006	-10000	0	-10000	0	0
EREG	0.082	0.12	0.29	67	-10000	0	67
BTC	0.018	0.008	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.025	0.063	-10000	0	-10000	0	0
ERBB4	0.009	0.021	-10000	0	-10000	0	0
STAT5B	0.02	0.002	-10000	0	-10000	0	0
YAP1	-0.033	0.14	-10000	0	-0.46	28	28
GRB2	0.02	0.005	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0.037	0.066	0.32	4	-10000	0	4
glial cell differentiation	-0.014	0.039	-10000	0	-10000	0	0
WWOX	0.019	0.005	-10000	0	-10000	0	0
cell proliferation	0.005	0.069	0.28	3	-0.31	1	4

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	0.028	0.009	-10000	0	-10000	0	0
CRKL	-0.026	0.1	-10000	0	-0.47	8	8
mol:PIP3	0.009	0.072	-10000	0	-0.84	2	2
AKT1	0.003	0.073	-10000	0	-0.74	2	2
PTK2B	0.019	0.006	-10000	0	-10000	0	0
RAPGEF1	-0.029	0.1	0.25	1	-0.45	8	9
RANBP10	0.02	0.004	-10000	0	-10000	0	0
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
HGF/MET/SHIP2	0.014	0.07	0.21	1	-0.17	34	35
MAP3K5	-0.036	0.1	-10000	0	-0.44	10	10
HGF/MET/CIN85/CBL/ENDOPHILINS	0.02	0.067	0.21	1	-0.16	33	34
AP1	-0.025	0.05	-10000	0	-0.18	19	19
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.019	0.006	-10000	0	-10000	0	0
apoptosis	-0.045	0.2	-10000	0	-0.67	26	26
STAT3 (dimer)	-0.028	0.086	-10000	0	-0.28	18	18
GAB1/CRKL/SHP2/PI3K	-0.003	0.094	-10000	0	-0.48	5	5
INPP5D	0.018	0.007	-10000	0	-10000	0	0
CBL/CRK	-0.014	0.099	-10000	0	-0.44	8	8
PTPN11	0.021	0.001	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.019	0.005	-10000	0	-10000	0	0
PTEN	0.019	0.005	-10000	0	-10000	0	0
ELK1	-0.008	0.052	0.24	8	-0.18	1	9
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.018	0.058	-10000	0	-0.23	5	5
PAK1	0	0.073	-10000	0	-0.71	2	2
HGF/MET/RANBP10	0.014	0.07	0.21	1	-0.17	34	35
HRAS	-0.04	0.13	-10000	0	-0.47	17	17
DOCK1	-0.031	0.098	-10000	0	-0.45	8	8
GAB1	-0.021	0.11	-10000	0	-0.48	8	8
CRK	-0.027	0.1	-10000	0	-0.46	8	8
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.052	0.16	-10000	0	-0.4	44	44
JUN	0.019	0.018	-10000	0	-0.29	1	1
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.014	0.049	-10000	0	-0.15	33	33
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
cell morphogenesis	0.014	0.13	0.25	12	-0.34	12	24
GRB2/SHC	-0.002	0.062	-10000	0	-0.17	10	10
FOS	-0.003	0.082	-10000	0	-0.29	22	22
GLMN	0.002	0.001	-10000	0	-10000	0	0
cell motility	-0.008	0.052	0.24	8	-0.18	1	9
HGF/MET/MUC20	0.004	0.063	0.19	1	-0.17	34	35
cell migration	-0.002	0.062	-10000	0	-0.16	10	10
GRB2	0.02	0.005	-10000	0	-10000	0	0
CBL	0.017	0.008	-10000	0	-10000	0	0
MET/RANBP10	0.028	0.008	-10000	0	-10000	0	0
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.02	0.074	-10000	0	-0.2	36	36
MET/MUC20	0.015	0.003	-10000	0	-10000	0	0
RAP1B	-0.029	0.1	0.25	3	-0.42	8	11
RAP1A	-0.033	0.096	0.23	1	-0.42	8	9
HGF/MET/RANBP9	0.015	0.068	0.21	1	-0.17	32	33
RAF1	-0.042	0.12	-10000	0	-0.45	17	17
STAT3	-0.027	0.086	-10000	0	-0.28	18	18
cell proliferation	-0.031	0.12	0.25	1	-0.32	35	36
RPS6KB1	-0.005	0.031	-10000	0	-0.26	1	1
MAPK3	-0.01	0.068	0.66	2	-10000	0	2
MAPK1	-0.008	0.08	0.53	5	-10000	0	5
RANBP9	0.019	0.005	-10000	0	-10000	0	0
MAPK8	-0.025	0.11	-10000	0	-0.45	10	10
SRC	-0.032	0.064	-10000	0	-0.24	11	11
PI3K	0.001	0.051	-10000	0	-0.16	7	7
MET/Glomulin	0.012	0.02	-10000	0	-10000	0	0
SOS1	0.02	0.003	-10000	0	-10000	0	0
MAP2K1	-0.042	0.12	-10000	0	-0.42	16	16
MET	0.02	0.004	-10000	0	-10000	0	0
MAP4K1	-0.033	0.11	-10000	0	-0.47	10	10
PTK2	0.019	0.006	-10000	0	-10000	0	0
MAP2K2	-0.042	0.12	-10000	0	-0.43	16	16
BAD	-0.001	0.071	-10000	0	-0.71	2	2
MAP2K4	-0.035	0.095	-10000	0	-0.42	9	9
SHP2/GRB2/SOS1/GAB1	-0.006	0.1	-10000	0	-0.41	8	8
INPPL1	0.02	0.004	-10000	0	-10000	0	0
PXN	0.021	0.001	-10000	0	-10000	0	0
SH3KBP1	0.02	0.004	-10000	0	-10000	0	0
HGS	-0.024	0.047	-10000	0	-0.14	36	36
PLCgamma1/PKC	0.014	0.004	-10000	0	-10000	0	0
HGF	-0.016	0.1	0.29	1	-0.29	34	35
RASA1	0.02	0.004	-10000	0	-10000	0	0
NCK1	0.015	0.009	-10000	0	-10000	0	0
PTPRJ	0.02	0.004	-10000	0	-10000	0	0
NCK/PLCgamma1	0	0.059	-10000	0	-0.16	29	29
PDPK1	0.006	0.074	-10000	0	-0.78	2	2
HGF/MET/SHIP	0.013	0.069	0.21	1	-0.17	34	35

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	-0.026	0.12	-10000	0	-0.32	11	11
CaM/Ca2+	0.015	0.003	-10000	0	-10000	0	0
AKT1	0.02	0.004	-10000	0	-10000	0	0
AKT2	0.02	0.005	-10000	0	-10000	0	0
STXBP4	0.02	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	-0.033	0.12	0.2	3	-0.32	16	19
YWHAZ	0.02	0.005	-10000	0	-10000	0	0
CALM1	0.02	0.005	-10000	0	-10000	0	0
YWHAQ	0.02	0.004	-10000	0	-10000	0	0
TBC1D4	-0.017	0.005	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.02	0.003	-10000	0	-10000	0	0
YWHAB	0.019	0.006	-10000	0	-10000	0	0
SNARE/Synip	0.037	0.014	-10000	0	-10000	0	0
YWHAG	0.02	0.004	-10000	0	-10000	0	0
ASIP	0.004	0.018	-10000	0	-10000	0	0
PRKCI	0.013	0.01	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0.015	0.003	-10000	0	-10000	0	0
RHOQ	0.02	0.004	-10000	0	-10000	0	0
GYS1	-0.006	0.003	-10000	0	-10000	0	0
PRKCZ	0.02	0.004	-10000	0	-10000	0	0
TRIP10	0.02	0.004	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.026	0.007	-10000	0	-10000	0	0
AS160/14-3-3	0.068	0.056	0.21	13	-10000	0	13
VAMP2	0.019	0.006	-10000	0	-10000	0	0
SLC2A4	-0.037	0.13	-10000	0	-0.35	16	16
STX4	0.02	0.002	-10000	0	-10000	0	0
GSK3B	0.007	0.004	-10000	0	-10000	0	0
SFN	0.28	0.067	0.29	274	-10000	0	274
LNPEP	0.02	0.004	-10000	0	-10000	0	0
YWHAE	0.019	0.006	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.016	0.007	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.024	0.012	-10000	0	-10000	0	0
CDKN1B	0.002	0.052	-10000	0	-0.29	7	7
CDKN1A	0.001	0.055	0.18	1	-0.29	8	9
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.02	0.004	-10000	0	-10000	0	0
FOXO3	0.001	0.055	-10000	0	-0.29	8	8
AKT1	-0.004	0.05	-10000	0	-0.3	8	8
BAD	0.02	0.003	-10000	0	-10000	0	0
AKT3	-0.005	0.051	-10000	0	-0.23	14	14
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.001	0.055	-10000	0	-0.29	8	8
AKT1/ASK1	0.025	0.062	0.22	1	-0.28	8	9
BAD/YWHAZ	0.038	0.013	-10000	0	-10000	0	0
RICTOR	0.018	0.007	-10000	0	-10000	0	0
RAF1	0.019	0.005	-10000	0	-10000	0	0
JNK cascade	-0.023	0.059	0.28	8	-10000	0	8
TSC1	0.001	0.054	-10000	0	-0.29	8	8
YWHAZ	0.02	0.005	-10000	0	-10000	0	0
AKT1/RAF1	0.025	0.065	0.23	1	-0.29	8	9
EP300	0.02	0.003	-10000	0	-10000	0	0
mol:GDP	0	0.053	-10000	0	-0.3	8	8
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0	0.053	-10000	0	-0.29	8	8
YWHAQ	0.02	0.004	-10000	0	-10000	0	0
TBC1D4	-0.007	0.002	-10000	0	-10000	0	0
MAP3K5	0.02	0.004	-10000	0	-10000	0	0
MAPKAP1	0.021	0.002	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.057	0.057	-10000	0	-0.19	14	14
YWHAH	0.02	0.003	-10000	0	-10000	0	0
AKT1S1	0.003	0.05	-10000	0	-0.29	6	6
CASP9	0.001	0.055	0.18	1	-0.29	8	9
YWHAB	0.019	0.006	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.016	0.056	0.22	2	-0.28	6	8
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.036	0.015	-10000	0	-10000	0	0
YWHAE	0.019	0.006	-10000	0	-10000	0	0
SRC	0.019	0.006	-10000	0	-10000	0	0
AKT2/p21CIP1	0	0.047	0.18	1	-0.26	7	8
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	-0.001	0.067	-10000	0	-0.32	11	11
CHUK	0.001	0.054	-10000	0	-0.29	8	8
BAD/BCL-XL	0.018	0.058	-10000	0	-0.28	8	8
mTORC2	0.023	0.01	-10000	0	-10000	0	0
AKT2	0.006	0.002	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.063	0.072	0.23	9	-0.24	1	10
PDPK1	0.02	0.004	-10000	0	-10000	0	0
MDM2	0.003	0.057	0.18	3	-0.29	8	11
MAPKKK cascade	-0.025	0.064	0.28	8	-0.22	2	10
MDM2/Cbp/p300	0.034	0.064	0.26	4	-0.28	6	10
TSC1/TSC2	0	0.066	0.3	5	-0.29	8	13
proteasomal ubiquitin-dependent protein catabolic process	0.032	0.061	0.25	4	-0.27	6	10
glucose import	-0.048	0.064	0.2	1	-0.15	83	84
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.005	0.057	0.21	4	-0.22	5	9
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.049	0.062	-10000	0	-0.15	83	83
GSK3A	0.003	0.049	-10000	0	-0.29	6	6
FOXO1	0.001	0.052	-10000	0	-0.29	7	7
GSK3B	0.021	0.074	-10000	0	-0.3	6	6
SFN	0.28	0.067	0.29	274	-10000	0	274
G1/S transition of mitotic cell cycle	0.034	0.092	0.25	19	-0.29	5	24
p27Kip1/14-3-3 family	0.073	0.063	0.23	8	-0.25	1	9
PRKACA	0.02	0.004	-10000	0	-10000	0	0
KPNA1	0.017	0.008	-10000	0	-10000	0	0
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
YWHAG	0.02	0.004	-10000	0	-10000	0	0
RHEB	0.02	0.004	-10000	0	-10000	0	0
CREBBP	0.02	0.004	-10000	0	-10000	0	0

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.02	0.004	-10000	0	-10000	0	0
EPHB2	0.021	0.005	-10000	0	-10000	0	0
EFNB1	-0.016	0.011	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.023	0.05	-10000	0	-0.15	16	16
Ephrin B2/EPHB1-2	0.018	0.044	-10000	0	-0.15	15	15
neuron projection morphogenesis	-0.021	0.04	-10000	0	-0.15	14	14
Ephrin B1/EPHB1-2/Tiam1	0.019	0.048	-10000	0	-0.16	16	16
DNM1	0.021	0.003	-10000	0	-10000	0	0
cell-cell signaling	0	0.004	-10000	0	-10000	0	0
MAP2K4	-0.018	0.076	-10000	0	-0.4	10	10
YES1	-0.015	0.12	-10000	0	-0.62	11	11
Ephrin B1/EPHB1-2/NCK2	0.021	0.046	-10000	0	-0.16	14	14
PI3K	0.006	0.077	-10000	0	-0.36	11	11
mol:GDP	0.018	0.046	-10000	0	-0.15	16	16
ITGA2B	0.019	0.03	0.29	1	-0.29	2	3
endothelial cell proliferation	0.026	0.008	-10000	0	-10000	0	0
FYN	-0.016	0.12	-10000	0	-0.62	11	11
MAP3K7	-0.016	0.078	-10000	0	-0.42	10	10
FGR	-0.012	0.12	-10000	0	-0.61	12	12
TIAM1	0.018	0.026	-10000	0	-0.29	2	2
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
RGS3	0.02	0.003	-10000	0	-10000	0	0
cell adhesion	-0.026	0.078	-10000	0	-0.36	11	11
LYN	-0.014	0.12	-10000	0	-0.62	11	11
Ephrin B1/EPHB1-2/Src Family Kinases	-0.022	0.12	-10000	0	-0.53	15	15
Ephrin B1/EPHB1-2	-0.013	0.086	-10000	0	-0.47	10	10
SRC	-0.01	0.12	-10000	0	-0.62	11	11
ITGB3	-0.016	0.1	-10000	0	-0.29	34	34
EPHB1	0.001	0.066	-10000	0	-0.29	14	14
EPHB4	0.02	0.005	-10000	0	-10000	0	0
RAC1	0.02	0.003	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.026	0.008	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	0.002	0.079	0.22	1	-0.21	35	36
BLK	-0.007	0.14	-10000	0	-0.62	12	12
HCK	-0.011	0.12	-10000	0	-0.62	11	11
regulation of stress fiber formation	-0.02	0.045	0.16	14	-10000	0	14
MAPK8	-0.024	0.077	-10000	0	-0.38	12	12
Ephrin B1/EPHB1-2/RGS3	0.021	0.046	-10000	0	-0.16	14	14
endothelial cell migration	-0.011	0.071	0.18	8	-0.35	10	18
NCK2	0.02	0.002	-10000	0	-10000	0	0
PTPN13	0.017	0.026	-10000	0	-0.4	1	1
regulation of focal adhesion formation	-0.02	0.045	0.16	14	-10000	0	14
chemotaxis	-0.02	0.045	0.16	14	-10000	0	14
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
Rac1/GTP	0.018	0.046	-10000	0	-0.15	16	16
angiogenesis	-0.013	0.086	-10000	0	-0.47	10	10
LCK	-0.012	0.12	-10000	0	-0.61	12	12

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.019	0.005	-10000	0	-10000	0	0
Syndecan-3/Src/Cortactin	-0.02	0.085	-10000	0	-0.49	1	1
Syndecan-3/Neurocan	0.019	0.029	-10000	0	-0.4	1	1
POMC	0.024	0.044	0.29	6	-0.29	1	7
EGFR	0.018	0.026	-10000	0	-0.29	2	2
Syndecan-3/EGFR	0.017	0.029	-10000	0	-0.4	1	1
AGRP	-0.017	0.003	-10000	0	-10000	0	0
NCSTN	0.019	0.005	-10000	0	-10000	0	0
PSENEN	0.02	0.005	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
APH1B	0.02	0.003	-10000	0	-10000	0	0
APH1A	0.019	0.005	-10000	0	-10000	0	0
NCAN	0.015	0.022	0.29	1	-10000	0	1
long-term memory	0.031	0.039	-10000	0	-0.38	1	1
Syndecan-3/IL8	0.12	0.097	0.28	13	-0.4	1	14
PSEN1	0.02	0.003	-10000	0	-10000	0	0
Src/Cortactin	0.027	0.01	-10000	0	-10000	0	0
FYN	0.015	0.04	-10000	0	-0.29	5	5
limb bud formation	0.004	0.024	-10000	0	-0.4	1	1
MC4R	-0.004	0.025	0.29	1	-10000	0	1
SRC	0.019	0.006	-10000	0	-10000	0	0
PTN	-0.099	0.15	-10000	0	-0.29	111	111
FGFR/FGF/Syndecan-3	0.004	0.024	-10000	0	-0.41	1	1
neuron projection morphogenesis	-0.045	0.072	-10000	0	-0.48	1	1
Syndecan-3/AgRP	0.017	0.026	-10000	0	-0.38	1	1
Syndecan-3/AgRP/MC4R	0.033	0.036	0.28	1	-0.36	1	2
Fyn/Cortactin	0.024	0.031	-10000	0	-0.2	5	5
SDC3	0.004	0.024	-10000	0	-0.41	1	1
GO:0007205	0	0	-10000	0	-10000	0	0
positive regulation of leukocyte migration	0.11	0.096	0.28	13	-0.39	1	14
IL8	0.17	0.14	0.29	159	-10000	0	159
Syndecan-3/Fyn/Cortactin	0.032	0.04	-10000	0	-0.39	1	1
Syndecan-3/CASK	0.003	0.023	-10000	0	-0.39	1	1
alpha-MSH/MC4R	0.031	0.032	0.22	7	-0.18	1	8
Gamma Secretase	0.051	0.024	-10000	0	-10000	0	0

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	0.025	0.094	0.41	3	-10000	0	3
MKNK1	0.02	0.002	-10000	0	-10000	0	0
MAPK14	0.028	0.063	-10000	0	-0.28	8	8
ATF2/c-Jun	0.003	0.057	-10000	0	-0.33	2	2
MAPK11	0.028	0.061	-10000	0	-0.28	7	7
MITF	-0.027	0.11	-10000	0	-0.25	47	47
MAPKAPK5	0.015	0.069	-10000	0	-0.33	8	8
KRT8	0.042	0.085	0.25	11	-0.31	6	17
MAPKAPK3	0.019	0.006	-10000	0	-10000	0	0
MAPKAPK2	0.019	0.005	-10000	0	-10000	0	0
p38alpha-beta/CK2	0.037	0.086	-10000	0	-0.38	8	8
CEBPB	0.017	0.072	0.27	3	-0.33	8	11
SLC9A1	0.015	0.072	-10000	0	-0.35	8	8
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	0.017	0.072	0.27	1	-0.32	8	9
p38alpha-beta/MNK1	0.045	0.074	-10000	0	-0.33	7	7
JUN	0.001	0.056	-10000	0	-0.33	2	2
PPARGC1A	-0.002	0.1	-10000	0	-0.31	20	20
USF1	0.015	0.07	0.31	1	-0.33	8	9
RAB5/GDP/GDI1	0.014	0.053	-10000	0	-0.24	8	8
NOS2	0.007	0.15	-10000	0	-0.84	8	8
DDIT3	0.015	0.069	-10000	0	-0.33	8	8
RAB5A	0.019	0.005	-10000	0	-10000	0	0
HSPB1	0.001	0.059	0.26	4	-0.27	7	11
p38alpha-beta/HBP1	0.043	0.073	-10000	0	-0.33	7	7
CREB1	0.012	0.073	-10000	0	-0.36	8	8
RAB5/GDP	0.014	0.004	-10000	0	-10000	0	0
EIF4E	-0.015	0.062	0.22	2	-0.29	7	9
RPS6KA4	0.015	0.069	-10000	0	-0.33	8	8
PLA2G4A	-0.018	0.065	0.2	3	-0.29	7	10
GDI1	0.015	0.07	0.27	1	-0.33	8	9
TP53	-0.005	0.078	-10000	0	-0.39	8	8
RPS6KA5	0.016	0.067	0.27	1	-0.33	7	8
ESR1	-0.06	0.13	-10000	0	-0.25	76	76
HBP1	0.02	0.004	-10000	0	-10000	0	0
MEF2C	-0.003	0.087	-10000	0	-0.28	20	20
MEF2A	0.016	0.066	-10000	0	-0.33	7	7
EIF4EBP1	0.012	0.069	-10000	0	-0.34	8	8
KRT19	0.026	0.08	0.25	4	-0.32	9	13
ELK4	0.017	0.074	0.32	3	-0.33	8	11
ATF6	0.015	0.07	0.31	1	-0.33	8	9
ATF1	0.014	0.07	0.22	1	-0.34	8	9
p38alpha-beta/MAPKAPK2	0.042	0.074	-10000	0	-0.33	7	7
p38alpha-beta/MAPKAPK3	0.042	0.073	-10000	0	-0.33	7	7

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.001	0.024	0.093	2	-0.17	1	3
NFATC2	-0.004	0.033	0.093	2	-0.17	7	9
NFATC3	-0.001	0.022	0.093	2	-10000	0	2
CD40LG	0.023	0.1	0.31	11	-10000	0	11
PTGS2	0.031	0.11	0.29	26	-10000	0	26
JUNB	0.02	0.004	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0.019	0.01	-10000	0	-10000	0	0
CaM/Ca2+	0.019	0.01	-10000	0	-10000	0	0
CALM1	0.022	0.007	-10000	0	-10000	0	0
JUN	0.022	0.019	-10000	0	-0.29	1	1
mol:Ca2+	0.002	0.004	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.015	0.005	-10000	0	-10000	0	0
FOSL1	0.039	0.069	0.29	20	-10000	0	20
CREM	0.02	0.004	-10000	0	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	0.048	0.068	0.25	13	-10000	0	13
FOS	-0.001	0.082	-10000	0	-0.29	22	22
IFNG	0.047	0.14	0.29	53	-10000	0	53
AP-1/NFAT1-c-4	0.08	0.13	0.44	14	-10000	0	14
FASLG	0.023	0.1	0.34	11	-10000	0	11
NFAT1-c-4/ICER1	0.002	0.055	0.19	3	-10000	0	3
IL2RA	0.026	0.11	0.33	17	-10000	0	17
FKBP12/FK506	0.014	0.004	-10000	0	-10000	0	0
CSF2	0.025	0.11	0.32	16	-10000	0	16
JunB/Fra1/NFAT1-c-4	0.045	0.065	0.21	20	-10000	0	20
IL4	0.02	0.098	0.26	21	-10000	0	21
IL2	-0.011	0.14	-10000	0	-0.82	8	8
IL3	-0.006	0.12	-10000	0	-0.56	12	12
FKBP1A	0.019	0.005	-10000	0	-10000	0	0
BATF3	0.019	0.005	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.019	0.005	-10000	0	-10000	0	0

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.03	0.14	-10000	0	-0.44	18	18
Syndecan-4/Syndesmos	0.015	0.1	-10000	0	-0.73	1	1
positive regulation of JNK cascade	-0.057	0.12	-10000	0	-0.41	8	8
Syndecan-4/ADAM12	0.017	0.1	-10000	0	-0.73	1	1
CCL5	0.02	0.003	-10000	0	-10000	0	0
Rac1/GDP	0.015	0.002	-10000	0	-10000	0	0
DNM2	0.02	0.004	-10000	0	-10000	0	0
ITGA5	0.018	0.026	-10000	0	-0.29	2	2
SDCBP	0.02	0.004	-10000	0	-10000	0	0
PLG	0.011	0.036	0.29	3	-0.12	1	4
ADAM12	0.02	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0.02	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.029	0.019	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	0.023	0.11	0.29	3	-0.56	2	5
Syndecan-4/CXCL12/CXCR4	-0.059	0.13	-10000	0	-0.44	8	8
Syndecan-4/Laminin alpha3	0.017	0.1	0.29	1	-0.71	1	2
MDK	0.02	0.004	-10000	0	-10000	0	0
Syndecan-4/FZD7	0.018	0.098	-10000	0	-0.73	1	1
Syndecan-4/Midkine	0.017	0.1	-10000	0	-0.73	1	1
FZD7	0.01	0.054	-10000	0	-0.29	9	9
Syndecan-4/FGFR1/FGF	-0.029	0.13	-10000	0	-0.4	10	10
THBS1	-0.03	0.11	-10000	0	-0.29	47	47
integrin-mediated signaling pathway	0.013	0.11	-10000	0	-0.78	1	1
positive regulation of MAPKKK cascade	-0.057	0.12	-10000	0	-0.41	8	8
Syndecan-4/TACI	0.018	0.1	0.29	1	-0.73	1	2
CXCR4	0.02	0.002	-10000	0	-10000	0	0
cell adhesion	-0.006	0.049	0.18	8	-0.21	8	16
Syndecan-4/Dynamin	0.018	0.1	-10000	0	-0.73	1	1
Syndecan-4/TSP1	0.004	0.11	-10000	0	-0.46	4	4
Syndecan-4/GIPC	0.016	0.1	-10000	0	-0.73	1	1
Syndecan-4/RANTES	0.016	0.1	-10000	0	-0.73	1	1
ITGB1	0.02	0.003	-10000	0	-10000	0	0
LAMA1	0.032	0.066	0.29	15	-0.29	2	17
LAMA3	0.02	0.024	0.29	1	-0.29	1	2
RAC1	0.02	0.003	-10000	0	-10000	0	0
PRKCA	0.004	0.13	0.77	8	-10000	0	8
Syndecan-4/alpha-Actinin	0.015	0.1	-10000	0	-0.73	1	1
TFPI	-0.009	0.09	-10000	0	-0.29	27	27
F2	0.02	0.015	-10000	0	-10000	0	0
alpha5/beta1 Integrin	0.028	0.02	-10000	0	-0.2	2	2
positive regulation of cell adhesion	0.012	0.1	-10000	0	-0.54	2	2
ACTN1	0.02	0.003	-10000	0	-10000	0	0
TNC	0.011	0.054	-10000	0	-0.29	9	9
Syndecan-4/CXCL12	-0.024	0.12	-10000	0	-0.44	8	8
FGF6	-0.016	0.004	-10000	0	-10000	0	0
RHOA	0.019	0.006	-10000	0	-10000	0	0
CXCL12	-0.17	0.15	-10000	0	-0.29	177	177
TNFRSF13B	0.017	0.02	0.29	1	-10000	0	1
FGF2	-0.074	0.14	-10000	0	-0.29	88	88
FGFR1	-0.021	0.1	-10000	0	-0.29	38	38
Syndecan-4/PI-4-5-P2	-0.002	0.09	0.24	1	-0.72	1	2
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.005	0.051	-10000	0	-0.26	9	9
cell migration	-0.016	0.012	-10000	0	-10000	0	0
PRKCD	0.013	0.022	-10000	0	-0.12	1	1
vasculogenesis	0.004	0.11	-10000	0	-0.44	4	4
SDC4	0.009	0.077	0.27	2	-10000	0	2
Syndecan-4/Tenascin C	0.013	0.11	-10000	0	-0.83	1	1
Syndecan-4/PI-4-5-P2/PKC alpha	-0.023	0.015	-10000	0	-10000	0	0
Syndecan-4/Syntenin	0.017	0.1	-10000	0	-0.73	1	1
MMP9	0.061	0.1	0.29	46	-10000	0	46
Rac1/GTP	-0.007	0.05	0.18	8	-0.21	8	16
cytoskeleton organization	0.015	0.099	-10000	0	-0.37	5	5
GIPC1	0.02	0.004	-10000	0	-10000	0	0
Syndecan-4/TFPI	0.012	0.11	-10000	0	-0.5	3	3

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.007	0.085	0.33	1	-0.38	1	2
CRKL	-0.02	0.059	0.22	5	-10000	0	5
mol:DAG	-0.007	0.062	-10000	0	-0.22	17	17
HRAS	-0.015	0.079	0.35	4	-10000	0	4
MAPK8	-0.022	0.056	0.16	15	-0.16	20	35
RAP1A	-0.02	0.06	0.21	6	-10000	0	6
GAB1	-0.02	0.059	0.28	3	-10000	0	3
MAPK14	-0.021	0.053	0.16	14	-0.16	17	31
EPO	-0.003	0.076	-10000	0	-0.3	18	18
PLCG1	-0.008	0.063	-10000	0	-0.22	17	17
EPOR/TRPC2/IP3 Receptors	0.016	0.017	-10000	0	-10000	0	0
RAPGEF1	0.02	0.002	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.024	0.053	-10000	0	-0.17	18	18
GAB1/SHC/GRB2/SOS1	-0.027	0.054	-10000	0	-10000	0	0
EPO/EPOR (dimer)	0.014	0.059	-10000	0	-0.21	18	18
IRS2	-0.023	0.062	0.22	5	-10000	0	5
STAT1	-0.006	0.07	-10000	0	-0.23	21	21
STAT5B	-0.006	0.069	-10000	0	-0.23	19	19
cell proliferation	-0.022	0.064	0.19	17	-0.15	19	36
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.034	0.046	-10000	0	-10000	0	0
TEC	-0.02	0.056	0.21	4	-10000	0	4
SOCS3	0.02	0.004	-10000	0	-10000	0	0
STAT1 (dimer)	-0.005	0.069	-10000	0	-0.22	21	21
JAK2	0.016	0.017	-10000	0	-10000	0	0
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.033	0.056	-10000	0	-0.15	18	18
EPO/EPOR	0.014	0.059	-10000	0	-0.21	18	18
LYN	0.019	0.008	-10000	0	-10000	0	0
TEC/VAV2	-0.026	0.053	0.19	3	-10000	0	3
elevation of cytosolic calcium ion concentration	0.016	0.017	-10000	0	-10000	0	0
SHC1	0.019	0.006	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	0.025	0.053	-10000	0	-0.17	18	18
mol:IP3	-0.007	0.062	-10000	0	-0.22	17	17
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.026	0.064	0.25	4	-10000	0	4
SH2B3	0.017	0.017	-10000	0	-10000	0	0
NFKB1	-0.021	0.054	0.16	15	-0.16	17	32
EPO/EPOR (dimer)/JAK2/SOCS3	-0.007	0.055	-10000	0	-0.19	21	21
PTPN6	-0.019	0.053	0.15	18	-10000	0	18
TEC/VAV2/GRB2	-0.029	0.053	0.26	1	-10000	0	1
EPOR	0.017	0.017	-10000	0	-10000	0	0
INPP5D	0.018	0.007	-10000	0	-10000	0	0
mol:GDP	-0.028	0.054	0.18	1	-10000	0	1
SOS1	0.02	0.003	-10000	0	-10000	0	0
PLCG2	0.02	0.004	-10000	0	-10000	0	0
CRKL/CBL/C3G	-0.027	0.052	0.19	3	-10000	0	3
VAV2	-0.021	0.057	0.28	2	-10000	0	2
CBL	-0.018	0.052	0.21	4	-10000	0	4
SHC/Grb2/SOS1	0.008	0.047	-10000	0	-10000	0	0
STAT5A	-0.006	0.069	-10000	0	-0.23	19	19
GRB2	0.02	0.005	-10000	0	-10000	0	0
STAT5 (dimer)	0.006	0.07	-10000	0	-0.3	3	3
LYN/PLCgamma2	0.028	0.011	-10000	0	-10000	0	0
PTPN11	0.021	0.001	-10000	0	-10000	0	0
BTK	-0.021	0.06	0.21	6	-10000	0	6
BCL2	-0.019	0.12	0.33	1	-0.59	7	8

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	-0.011	0.042	0.17	6	-0.18	11	17
RFC1	-0.008	0.032	0.16	4	-0.18	6	10
PRKDC	-0.005	0.052	0.19	12	-0.18	10	22
RIPK1	0.018	0.009	-10000	0	-10000	0	0
CASP7	-0.004	0.098	-10000	0	-0.58	8	8
FASLG/FAS/FADD/FAF1	0.005	0.029	0.15	1	-0.18	1	2
MAP2K4	0.007	0.094	0.28	1	-0.32	11	12
mol:ceramide	0.009	0.036	-10000	0	-10000	0	0
GSN	-0.011	0.042	0.17	6	-0.18	11	17
FASLG/FAS/FADD/FAF1/Caspase 8	0.003	0.041	-10000	0	-0.3	1	1
FAS	0.02	0.005	-10000	0	-10000	0	0
BID	-0.021	0.009	-10000	0	-10000	0	0
MAP3K1	0.023	0.11	0.26	3	-0.4	10	13
MAP3K7	0.02	0.004	-10000	0	-10000	0	0
RB1	-0.012	0.036	-10000	0	-0.18	10	10
CFLAR	0.018	0.009	-10000	0	-10000	0	0
HGF/MET	0.013	0.072	0.21	1	-0.18	35	36
ARHGDIB	-0.01	0.044	0.22	3	-0.18	11	14
FADD	0.02	0.006	-10000	0	-10000	0	0
actin filament polymerization	0.01	0.042	0.18	11	-0.17	6	17
NFKB1	0.011	0.079	-10000	0	-0.56	5	5
MAPK8	0.002	0.091	0.25	2	-0.56	2	4
DFFA	-0.011	0.037	-10000	0	-0.18	10	10
DNA fragmentation during apoptosis	-0.011	0.037	0.14	4	-0.18	10	14
FAS/FADD/MET	0.037	0.015	-10000	0	-10000	0	0
CFLAR/RIP1	0.026	0.014	-10000	0	-10000	0	0
FAIM3	0.018	0.008	-10000	0	-10000	0	0
FAF1	0.021	0.004	-10000	0	-10000	0	0
PARP1	-0.011	0.04	0.16	5	-0.18	11	16
DFFB	-0.011	0.037	0.14	4	-0.18	10	14
CHUK	0.004	0.066	-10000	0	-0.52	4	4
FASLG	0.023	0.028	0.29	3	-10000	0	3
FAS/FADD	0.028	0.01	-10000	0	-10000	0	0
HGF	-0.016	0.1	0.29	1	-0.29	34	35
LMNA	-0.01	0.04	0.22	4	-0.17	6	10
CASP6	-0.01	0.032	0.14	4	-0.18	7	11
CASP10	0.02	0.006	-10000	0	-10000	0	0
CASP3	0	0.021	0.18	4	-10000	0	4
PTPN13	0.017	0.026	-10000	0	-0.29	2	2
CASP8	-0.019	0.007	-10000	0	-10000	0	0
IL6	0.02	0.083	-10000	0	-0.53	2	2
MET	0.02	0.004	-10000	0	-10000	0	0
ICAD/CAD	-0.015	0.034	-10000	0	-0.17	10	10
FASLG/FAS/FADD/FAF1/Caspase 10	0.009	0.036	-10000	0	-10000	0	0
activation of caspase activity by cytochrome c	-0.021	0.009	-10000	0	-10000	0	0
PAK2	0.05	0.1	0.22	76	-0.18	4	80
BCL2	0.014	0.04	-10000	0	-0.29	5	5

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.025	0.077	-10000	0	-0.21	33	33
FZD6	0.019	0.005	-10000	0	-10000	0	0
WNT6	0.011	0.048	-10000	0	-0.29	7	7
WNT4	0.016	0.036	-10000	0	-0.29	4	4
FZD3	0.009	0.054	-10000	0	-0.29	9	9
WNT5A	0.019	0.006	-10000	0	-10000	0	0
WNT11	0.012	0.053	0.29	1	-0.29	8	9

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.085	0.089	-10000	0	-0.45	3	3
RAD9A	0.02	0.003	-10000	0	-10000	0	0
AP1	0.012	0.062	-10000	0	-0.2	22	22
IFNAR2	0.02	0.003	-10000	0	-10000	0	0
AKT1	-0.039	0.075	-10000	0	-0.32	6	6
ER alpha/Oestrogen	-0.054	0.098	-10000	0	-0.2	95	95
NFX1/SIN3/HDAC complex	0.01	0.03	-10000	0	-0.18	1	1
EGF	0.003	0.066	-10000	0	-0.29	14	14
SMG5	0.019	0.005	-10000	0	-10000	0	0
SMG6	0.019	0.006	-10000	0	-10000	0	0
SP3/HDAC2	0.029	0.007	-10000	0	-10000	0	0
TERT/c-Abl	-0.089	0.086	-10000	0	-0.44	3	3
SAP18	0.02	0.004	-10000	0	-10000	0	0
MRN complex	0.034	0.017	-10000	0	-10000	0	0
WT1	-0.24	0.12	-10000	0	-0.29	240	240
WRN	0.019	0.006	-10000	0	-10000	0	0
SP1	0.02	0.003	-10000	0	-10000	0	0
SP3	0.02	0.003	-10000	0	-10000	0	0
TERF2IP	0.02	0.004	-10000	0	-10000	0	0
Telomerase/Nucleolin	-0.083	0.087	-10000	0	-0.41	3	3
Mad/Max	0.03	0.006	-10000	0	-10000	0	0
TERT	-0.086	0.09	-10000	0	-0.46	3	3
CCND1	-0.079	0.083	-10000	0	-10000	0	0
MAX	0.02	0.003	-10000	0	-10000	0	0
RBBP7	0.02	0.004	-10000	0	-10000	0	0
RBBP4	0.021	0.001	-10000	0	-10000	0	0
TERF2	-0.009	0.03	-10000	0	-10000	0	0
PTGES3	0.02	0.002	-10000	0	-10000	0	0
SIN3A	0.02	0.004	-10000	0	-10000	0	0
Telomerase/911	0.008	0.041	-10000	0	-10000	0	0
CDKN1B	0.001	0.042	-10000	0	-10000	0	0
RAD1	0.018	0.007	-10000	0	-10000	0	0
XRCC5	0.019	0.006	-10000	0	-10000	0	0
XRCC6	0.02	0.003	-10000	0	-10000	0	0
SAP30	0.02	0.004	-10000	0	-10000	0	0
TRF2/PARP2	0.032	0.016	-10000	0	-10000	0	0
UBE3A	0.02	0.004	-10000	0	-10000	0	0
JUN	0.019	0.018	-10000	0	-0.29	1	1
E6	0	0	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.015	0.003	-10000	0	-10000	0	0
FOS	-0.003	0.082	-10000	0	-0.29	22	22
IFN-gamma/IRF1	0.062	0.071	0.22	50	-10000	0	50
PARP2	0.02	0.003	-10000	0	-10000	0	0
BLM	0.085	0.12	0.29	69	-10000	0	69
Telomerase	-0.014	0.062	-10000	0	-0.42	2	2
IRF1	0.02	0.005	-10000	0	-10000	0	0
ESR1	-0.082	0.14	-10000	0	-0.29	95	95
KU/TER	0.027	0.01	-10000	0	-10000	0	0
ATM/TRF2	0.019	0.028	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.012	0.039	-10000	0	-0.23	2	2
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.012	0.04	-10000	0	-0.23	2	2
HDAC1	0.021	0.001	-10000	0	-10000	0	0
HDAC2	0.02	0.003	-10000	0	-10000	0	0
ATM	0.008	0.009	-10000	0	-10000	0	0
SMAD3	-0.018	0.004	-10000	0	-10000	0	0
ABL1	0.02	0.002	-10000	0	-10000	0	0
MXD1	0.02	0.003	-10000	0	-10000	0	0
MRE11A	0.018	0.007	-10000	0	-10000	0	0
HUS1	0.02	0.002	-10000	0	-10000	0	0
RPS6KB1	0.02	0.003	-10000	0	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.084	0.1	-10000	0	-0.44	6	6
NR2F2	-0.006	0.085	-10000	0	-0.29	24	24
MAPK3	-0.018	0.004	-10000	0	-10000	0	0
MAPK1	-0.018	0.004	-10000	0	-10000	0	0
TGFB1/TGF beta receptor Type II	0.02	0.004	-10000	0	-10000	0	0
NFKB1	0.02	0.003	-10000	0	-10000	0	0
HNRNPC	0.02	0.003	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.008	0.009	-10000	0	-10000	0	0
NBN	0.02	0.004	-10000	0	-10000	0	0
EGFR	0.018	0.026	-10000	0	-0.29	2	2
mol:Oestrogen	0	0	-10000	0	-10000	0	0
EGF/EGFR	0.017	0.052	-10000	0	-0.2	15	15
MYC	0.015	0.036	-10000	0	-0.29	4	4
IL2	0.018	0.004	-10000	0	-10000	0	0
KU	0.027	0.01	-10000	0	-10000	0	0
RAD50	0.02	0.005	-10000	0	-10000	0	0
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
TGFB1	0.02	0.004	-10000	0	-10000	0	0
TRF2/BLM	0.073	0.079	0.21	67	-10000	0	67
FRAP1	0	0	-10000	0	-10000	0	0
KU/TERT	-0.082	0.09	-10000	0	-0.42	3	3
SP1/HDAC2	0.03	0.007	-10000	0	-10000	0	0
PINX1	0.019	0.006	-10000	0	-10000	0	0
Telomerase/EST1A	-0.084	0.088	-10000	0	-0.41	3	3
Smad3/Myc	-0.021	0.02	-10000	0	-0.17	4	4
911 complex	0.034	0.016	-10000	0	-10000	0	0
IFNG	0.069	0.1	0.3	51	-10000	0	51
Telomerase/PinX1	-0.085	0.085	-10000	0	-0.41	3	3
Telomerase/AKT1/mTOR/p70S6K	-0.035	0.072	-10000	0	-0.31	11	11
SIN3B	0.02	0.003	-10000	0	-10000	0	0
YWHAE	0.019	0.006	-10000	0	-10000	0	0
Telomerase/EST1B	-0.08	0.086	-10000	0	-0.42	3	3
response to DNA damage stimulus	-0.011	0.036	-10000	0	-0.1	40	40
MRN complex/TRF2/Rap1	0.046	0.026	-10000	0	-10000	0	0
TRF2/WRN	0.03	0.017	-10000	0	-10000	0	0
Telomerase/hnRNP C1/C2	-0.083	0.088	-10000	0	-0.41	3	3
E2F1	0.024	0.04	0.29	6	-10000	0	6
ZNFX1	0.019	0.005	-10000	0	-10000	0	0
PIF1	0.025	0.036	0.29	5	-10000	0	5
NCL	0.018	0.007	-10000	0	-10000	0	0
DKC1	0.02	0.004	-10000	0	-10000	0	0
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	-0.017	0.006	-10000	0	-10000	0	0
SMARCC1	0.003	0.011	-10000	0	-10000	0	0
REL	0.018	0.011	-10000	0	-10000	0	0
HDAC7	-0.009	0.086	0.19	2	-0.25	8	10
JUN	0.019	0.019	-10000	0	-0.29	1	1
EP300	0.02	0.003	-10000	0	-10000	0	0
KAT2B	0.02	0.005	-10000	0	-10000	0	0
KAT5	0.02	0.004	-10000	0	-10000	0	0
MAPK14	-0.005	0.022	0.14	1	-10000	0	1
FOXO1	0.017	0.026	-10000	0	-0.29	2	2
T-DHT/AR	0.021	0.12	0.23	12	-0.26	8	20
MAP2K6	0.021	0.021	0.29	1	-10000	0	1
BRM/BAF57	0.03	0.01	-10000	0	-10000	0	0
MAP2K4	0.018	0.015	-10000	0	-10000	0	0
SMARCA2	0.02	0.006	-10000	0	-10000	0	0
PDE9A	-0.019	0.25	-10000	0	-0.75	26	26
NCOA2	0.016	0.036	-10000	0	-0.29	4	4
CEBPA	0.018	0.009	-10000	0	-10000	0	0
EHMT2	0.02	0.005	-10000	0	-10000	0	0
cell proliferation	0.025	0.13	0.32	19	-0.32	6	25
NR0B1	0.013	0.056	0.29	10	-10000	0	10
EGR1	0.012	0.051	-10000	0	-0.29	8	8
RXRs/9cRA	0.035	0.02	0.2	1	-0.16	1	2
AR/RACK1/Src	-0.008	0.079	0.21	11	-10000	0	11
AR/GR	-0.066	0.11	0.29	1	-0.21	72	73
GNB2L1	0.02	0.004	-10000	0	-10000	0	0
PKN1	0.02	0.004	-10000	0	-10000	0	0
RCHY1	0.02	0.004	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0.001	-10000	0	-10000	0	0
MAPK8	-0.006	0.023	-10000	0	-0.2	1	1
T-DHT/AR/TIF2/CARM1	-0.014	0.077	0.28	1	-0.32	2	3
SRC	-0.009	0.045	0.2	9	-0.15	1	10
NR3C1	0.02	0.004	-10000	0	-10000	0	0
KLK3	0.057	0.12	0.4	4	-10000	0	4
APPBP2	0.021	0.015	-10000	0	-10000	0	0
TRIM24	0.02	0.006	-10000	0	-10000	0	0
T-DHT/AR/TIP60	-0.018	0.065	0.19	1	-0.29	1	2
TMPRSS2	0.084	0.17	0.46	15	-0.53	5	20
RXRG	0.008	0.03	0.29	1	-0.29	1	2
mol:9cRA	0	0.001	-10000	0	-10000	0	0
RXRA	0.021	0.002	-10000	0	-10000	0	0
RXRB	0.02	0.004	-10000	0	-10000	0	0
CARM1	0.02	0.004	-10000	0	-10000	0	0
NR2C2	0.017	0.026	-10000	0	-0.29	2	2
KLK2	-0.004	0.084	0.32	7	-10000	0	7
AR	-0.062	0.095	0.13	1	-0.2	91	92
SENP1	0.021	0.003	-10000	0	-10000	0	0
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
MDM2	0.018	0.012	-10000	0	-10000	0	0
SRY	-0.001	0.005	-10000	0	-0.025	11	11
GATA2	0.009	0.048	-10000	0	-0.29	7	7
MYST2	0	0.001	-10000	0	-10000	0	0
HOXB13	0.14	0.14	0.3	134	-10000	0	134
T-DHT/AR/RACK1/Src	-0.008	0.078	0.21	12	-10000	0	12
positive regulation of transcription	0.009	0.048	-10000	0	-0.29	7	7
DNAJA1	0.021	0.015	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.005	0.003	-10000	0	-10000	0	0
NCOA1	0.025	0.02	-10000	0	-10000	0	0
SPDEF	0.054	0.12	0.3	45	-0.29	8	53
T-DHT/AR/TIF2	-0.023	0.07	0.18	1	-0.27	7	8
T-DHT/AR/Hsp90	-0.018	0.065	0.18	2	-0.29	1	3
GSK3B	0.016	0.013	-10000	0	-10000	0	0
NR2C1	0.019	0.009	-10000	0	-10000	0	0
mol:T-DHT	-0.01	0.031	0.24	1	-0.16	1	2
SIRT1	0.02	0.003	-10000	0	-10000	0	0
ZMIZ2	0.018	0.012	-10000	0	-10000	0	0
POU2F1	0.05	0.066	-10000	0	-0.12	1	1
T-DHT/AR/DAX-1	-0.013	0.074	0.21	8	-0.29	1	9
CREBBP	0.02	0.004	-10000	0	-10000	0	0
SMARCE1	0.021	0.004	-10000	0	-10000	0	0

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	0.045	0.068	0.22	2	-10000	0	2
TBX21	0.029	0.16	-10000	0	-1	1	1
B2M	0.02	0.005	-10000	0	-10000	0	0
TYK2	0.014	0.028	-10000	0	-10000	0	0
IL12RB1	0.014	0.028	-10000	0	-10000	0	0
GADD45B	0.009	0.16	-10000	0	-0.59	6	6
IL12RB2	0.074	0.12	0.29	61	-10000	0	61
GADD45G	-0.05	0.33	-10000	0	-0.99	28	28
natural killer cell activation	0	0.014	0.057	3	-0.046	2	5
RELB	0.02	0.004	-10000	0	-10000	0	0
RELA	0.02	0.003	-10000	0	-10000	0	0
IL18	0.014	0.036	0.3	3	-10000	0	3
IL2RA	0.027	0.042	0.29	7	-10000	0	7
IFNG	0.067	0.1	0.29	51	-10000	0	51
STAT3 (dimer)	0.017	0.15	-10000	0	-0.55	4	4
HLA-DRB5	-0.001	0.006	-10000	0	-0.022	19	19
FASLG	0.044	0.16	-10000	0	-10000	0	0
NF kappa B2 p52/RelB	0.035	0.14	-10000	0	-0.53	3	3
CD4	0.016	0.015	-10000	0	-10000	0	0
SOCS1	0.02	0.005	-10000	0	-10000	0	0
EntrezGene:6955	-0.001	0.007	0.025	2	-0.024	21	23
CD3D	0.015	0.024	0.32	1	-10000	0	1
CD3E	0.014	0.016	-10000	0	-10000	0	0
CD3G	0.015	0.024	0.32	1	-10000	0	1
IL12Rbeta2/JAK2	0.062	0.084	0.22	56	-10000	0	56
CCL3	0.032	0.15	-10000	0	-10000	0	0
CCL4	0.032	0.15	-10000	0	-10000	0	0
HLA-A	0	0.002	0.025	2	-10000	0	2
IL18/IL18R	0.034	0.053	0.22	3	-0.18	1	4
NOS2	0.009	0.22	-10000	0	-0.99	9	9
IL12/IL12R/TYK2/JAK2/SPHK2	0.042	0.068	0.2	1	-10000	0	1
IL1R1	0.024	0.17	-10000	0	-1	3	3
IL4	-0.007	0.027	-10000	0	-10000	0	0
JAK2	0.014	0.027	-10000	0	-10000	0	0
EntrezGene:6957	-0.001	0.006	0.023	2	-0.021	19	21
TCR/CD3/MHC I/CD8	-0.028	0.096	0.28	2	-0.28	35	37
RAB7A	0.019	0.22	-10000	0	-0.67	8	8
lysosomal transport	0.02	0.21	-10000	0	-0.64	8	8
FOS	-0.06	0.3	-10000	0	-1	24	24
STAT4 (dimer)	0.015	0.18	-10000	0	-0.6	5	5
STAT5A (dimer)	0.065	0.17	0.48	4	-0.53	3	7
GZMA	0.027	0.15	-10000	0	-1.1	1	1
GZMB	0.037	0.15	-10000	0	-10000	0	0
HLX	0.019	0.005	-10000	0	-10000	0	0
LCK	0.027	0.15	-10000	0	-0.56	3	3
TCR/CD3/MHC II/CD4	-0.015	0.077	-10000	0	-0.26	22	22
IL2/IL2R	0.054	0.032	0.21	10	-10000	0	10
MAPK14	-0.018	0.23	-10000	0	-0.77	11	11
CCR5	0.002	0.16	-10000	0	-0.58	2	2
IL1B	0.064	0.11	0.29	51	-10000	0	51
STAT6	0.028	0.068	-10000	0	-0.36	1	1
STAT4	0.02	0.004	-10000	0	-10000	0	0
STAT3	0.02	0.002	-10000	0	-10000	0	0
STAT1	0.02	0.004	-10000	0	-10000	0	0
NFKB1	0.02	0.003	-10000	0	-10000	0	0
NFKB2	0.02	0.003	-10000	0	-10000	0	0
IL12B	0.017	0.043	0.3	4	-10000	0	4
CD8A	0.022	0.018	0.32	1	-10000	0	1
CD8B	0.024	0.041	0.3	5	-0.29	1	6
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.045	0.068	-10000	0	-0.22	2	2
IL2RB	0.02	0.002	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.016	0.17	-10000	0	-0.56	5	5
IL2RG	0.023	0.028	0.29	3	-10000	0	3
IL12	0.024	0.053	0.22	11	-10000	0	11
STAT5A	0.02	0.002	-10000	0	-10000	0	0
CD247	0.016	0.015	-10000	0	-10000	0	0
IL2	-0.001	0.019	-10000	0	-10000	0	0
SPHK2	0.02	0.004	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.017	0.051	0.3	7	-10000	0	7
IL12/IL12R/TYK2/JAK2	0.023	0.15	-10000	0	-0.58	3	3
MAP2K3	-0.021	0.24	-10000	0	-0.81	11	11
RIPK2	0.02	0.004	-10000	0	-10000	0	0
MAP2K6	-0.013	0.22	-10000	0	-0.71	11	11
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.002	0.006	-10000	0	-0.025	21	21
IL18RAP	0.014	0.022	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	0.021	0.036	-10000	0	-10000	0	0
EOMES	-0.038	0.14	-10000	0	-0.53	19	19
STAT1 (dimer)	0.044	0.17	0.46	4	-0.55	4	8
T cell proliferation	-0.002	0.16	-10000	0	-0.5	8	8
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.013	0.028	-10000	0	-0.29	1	1
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.022	0.17	-10000	0	-0.5	17	17
ATF2	-0.018	0.22	-10000	0	-0.72	11	11

×

IFN-gamma 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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.068	0.061	0.2	48	-10000	0	48
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	0.02	0.003	-10000	0	-10000	0	0
STAT1 (dimer)/Cbp/p300	-0.007	0.05	-10000	0	-10000	0	0
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.042	0.017	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.019	0.036	-10000	0	-10000	0	0
CaM/Ca2+	0.063	0.055	-10000	0	-10000	0	0
RAP1A	0.021	0.002	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	-0.002	0.049	0.18	2	-10000	0	2
AKT1	0.046	0.088	0.23	16	-10000	0	16
MAP2K1	-0.012	0.04	0.16	2	-10000	0	2
MAP3K11	-0.006	0.044	0.18	2	-10000	0	2
IFNGR1	0.021	0.008	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.073	0.15	-10000	0	-0.3	80	80
Rap1/GTP	-0.025	0.026	-10000	0	-10000	0	0
CRKL/C3G	0.03	0.006	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.075	0.063	-10000	0	-10000	0	0
CEBPB	0.01	0.065	-10000	0	-0.32	3	3
STAT3	0.02	0.002	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.069	0.1	-10000	0	-0.72	3	3
STAT1	-0.007	0.042	0.18	2	-10000	0	2
CALM1	0.02	0.005	-10000	0	-10000	0	0
IFN-gamma (dimer)	0.066	0.11	0.3	51	-10000	0	51
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
STAT1 (dimer)/PIAS1	-0.007	0.047	0.18	2	-10000	0	2
CEBPB/PTGES2/Cbp/p300	0.016	0.043	-10000	0	-0.23	2	2
mol:Ca2+	0.064	0.058	0.19	48	-10000	0	48
MAPK3	0.002	0.074	-10000	0	-0.71	2	2
STAT1 (dimer)	-0.023	0.049	-10000	0	-10000	0	0
MAPK1	-0.002	0.083	-10000	0	-0.69	3	3
JAK2	0.02	0.009	-10000	0	-10000	0	0
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
JAK1	0.02	0.01	-10000	0	-10000	0	0
CAMK2D	0.02	0.003	-10000	0	-10000	0	0
DAPK1	0.008	0.059	0.24	1	-0.52	1	2
SMAD7	0.006	0.043	0.15	4	-10000	0	4
CBL/CRKL/C3G	-0.006	0.049	0.18	2	-10000	0	2
PI3K	0.042	0.052	-10000	0	-10000	0	0
IFNG	0.066	0.11	0.3	51	-10000	0	51
apoptosis	0.01	0.062	-10000	0	-0.36	4	4
CAMK2G	0.02	0.003	-10000	0	-10000	0	0
STAT3 (dimer)	0.02	0.002	-10000	0	-10000	0	0
CAMK2A	-0.074	0.14	-10000	0	-0.29	87	87
CAMK2B	0.041	0.072	0.29	22	-10000	0	22
FRAP1	0.04	0.082	0.21	19	-10000	0	19
PRKCD	0.045	0.089	0.23	17	-10000	0	17
RAP1B	0.02	0.003	-10000	0	-10000	0	0
negative regulation of cell growth	-0.019	0.036	-10000	0	-10000	0	0
PTPN2	0.02	0.004	-10000	0	-10000	0	0
EP300	0.02	0.003	-10000	0	-10000	0	0
IRF1	-0.01	0.046	0.26	3	-10000	0	3
STAT1 (dimer)/PIASy	-0.008	0.046	0.18	2	-10000	0	2
SOCS1	0.007	0.11	-10000	0	-1	3	3
mol:GDP	-0.006	0.046	0.17	2	-10000	0	2
CASP1	0.005	0.043	0.17	4	-10000	0	4
PTGES2	0.021	0.002	-10000	0	-10000	0	0
IRF9	0.002	0.029	0.15	1	-10000	0	1
mol:PI-3-4-5-P3	0.031	0.04	-10000	0	-10000	0	0
RAP1/GDP	-0.019	0.039	-10000	0	-10000	0	0
CBL	-0.004	0.041	0.18	2	-10000	0	2
MAP3K1	-0.006	0.043	0.18	2	-10000	0	2
PIAS1	0.02	0.003	-10000	0	-10000	0	0
PIAS4	0.02	0.005	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.019	0.036	-10000	0	-10000	0	0
PTPN11	-0.002	0.045	0.15	16	-10000	0	16
CREBBP	0.02	0.004	-10000	0	-10000	0	0
RAPGEF1	0.02	0.002	-10000	0	-10000	0	0

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	-0.018	0.004	-10000	0	-10000	0	0
MAP4K4	-0.003	0.049	0.22	1	-0.26	1	2
BAG4	0.019	0.005	-10000	0	-10000	0	0
PKC zeta/ceramide	0.008	0.041	-10000	0	-0.19	11	11
NFKBIA	0.02	0.003	-10000	0	-10000	0	0
BIRC3	0.017	0.018	0.29	1	-10000	0	1
BAX	0.002	0.044	-10000	0	-0.35	4	4
RIPK1	0.02	0.005	-10000	0	-10000	0	0
AKT1	-0.003	0.087	0.65	5	-10000	0	5
BAD	-0.007	0.036	0.2	1	-0.18	10	11
SMPD1	-0.001	0.063	0.16	10	-0.23	11	21
RB1	-0.009	0.036	-10000	0	-0.18	11	11
FADD/Caspase 8	-0.007	0.076	0.21	3	-0.33	7	10
MAP2K4	-0.012	0.038	0.18	2	-0.18	11	13
NSMAF	0.02	0.004	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.011	0.037	0.18	2	-0.18	10	12
EGF	0.003	0.066	-10000	0	-0.29	14	14
mol:ceramide	-0.003	0.039	-10000	0	-0.19	11	11
MADD	0.02	0.004	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.017	0.006	-10000	0	-10000	0	0
ASAH1	0.019	0.006	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.009	0.036	-10000	0	-0.18	11	11
cell proliferation	-0.049	0.066	0.16	2	-0.26	8	10
BID	-0.003	0.12	-10000	0	-0.6	7	7
MAP3K1	-0.007	0.04	0.19	2	-0.18	11	13
EIF2A	0.039	0.091	0.17	83	-0.18	6	89
TRADD	0.02	0.004	-10000	0	-10000	0	0
CRADD	0.021	0.001	-10000	0	-10000	0	0
MAPK3	-0.013	0.037	0.17	2	-0.17	10	12
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.013	0.037	0.17	2	-0.17	11	13
Cathepsin D/ceramide	0.009	0.041	-10000	0	-0.19	11	11
FADD	0	0.046	0.22	1	-0.26	1	2
KSR1	-0.008	0.037	0.2	1	-0.19	10	11
MAPK8	-0.012	0.052	-10000	0	-0.18	12	12
PRKRA	-0.005	0.046	0.19	6	-0.19	11	17
PDGFA	0.02	0.003	-10000	0	-10000	0	0
TRAF2	0.02	0.003	-10000	0	-10000	0	0
IGF1	-0.079	0.14	-10000	0	-0.29	93	93
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.003	0.039	-10000	0	-0.19	11	11
CTSD	0.02	0.005	-10000	0	-10000	0	0
regulation of nitric oxide biosynthetic process	0.03	0.006	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.052	0.07	0.18	2	-0.28	8	10
PRKCD	0.019	0.006	-10000	0	-10000	0	0
PRKCZ	0.02	0.004	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.017	0.006	-10000	0	-10000	0	0
RelA/NF kappa B1	0.03	0.006	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.021	0.001	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0	0.043	0.25	1	-10000	0	1
TNFR1A/BAG4/TNF-alpha	0.038	0.025	0.21	4	-10000	0	4
mol:Sphingosine-1-phosphate	-0.018	0.004	-10000	0	-10000	0	0
MAP2K1	-0.015	0.038	0.16	4	-0.18	10	14
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.02	0.003	-10000	0	-10000	0	0
CYCS	0.002	0.039	0.13	3	-0.18	4	7
TNFRSF1A	0.019	0.005	-10000	0	-10000	0	0
NFKB1	0.02	0.003	-10000	0	-10000	0	0
TNFR1A/BAG4	0.027	0.01	-10000	0	-10000	0	0
EIF2AK2	-0.005	0.049	0.18	11	-0.18	9	20
TNF-alpha/TNFR1A/FAN	0.038	0.025	0.21	4	-10000	0	4
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	-0.005	0.1	-10000	0	-0.39	15	15
MAP2K2	-0.016	0.035	0.17	2	-0.18	10	12
SMPD3	0.003	0.052	0.19	3	-0.26	6	9
TNF	0.023	0.032	0.29	4	-10000	0	4
PKC zeta/PAR4	0.03	0.006	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	0.012	0.043	0.16	12	-0.12	8	20
NF kappa B1/RelA/I kappa B alpha	0.055	0.02	-10000	0	-10000	0	0
AIFM1	0.002	0.039	0.13	4	-0.18	4	8
BCL2	0.014	0.04	-10000	0	-0.29	5	5

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	-0.013	0.098	0.22	2	-0.32	15	17
BAG4	0.019	0.005	-10000	0	-10000	0	0
BAD	-0.007	0.041	0.13	6	-0.14	7	13
NFKBIA	0.02	0.003	-10000	0	-10000	0	0
BIRC3	0.017	0.018	0.29	1	-10000	0	1
BAX	-0.004	0.048	0.16	9	-0.14	8	17
EnzymeConsortium:3.1.4.12	-0.001	0.026	0.075	6	-0.079	10	16
IKBKB	-0.015	0.096	0.2	2	-0.4	7	9
MAP2K2	-0.012	0.04	0.21	3	-0.19	2	5
MAP2K1	-0.011	0.044	0.17	6	-0.19	2	8
SMPD1	-0.005	0.035	0.096	2	-0.14	11	13
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	-0.011	0.1	0.24	4	-0.36	11	15
MAP2K4	-0.008	0.038	0.15	4	-0.18	2	6
protein ubiquitination	-0.014	0.1	0.21	6	-0.42	7	13
EnzymeConsortium:2.7.1.37	-0.013	0.044	0.19	4	-0.2	2	6
response to UV	0	0	0.002	5	-0.002	1	6
RAF1	-0.009	0.042	0.19	4	-0.19	2	6
CRADD	0.021	0.001	-10000	0	-10000	0	0
mol:ceramide	-0.003	0.041	0.11	6	-0.13	12	18
I-kappa-B-alpha/RELA/p50/ubiquitin	0.027	0.006	-10000	0	-10000	0	0
MADD	0.02	0.004	-10000	0	-10000	0	0
MAP3K1	-0.006	0.041	0.13	6	-0.14	7	13
TRADD	0.02	0.004	-10000	0	-10000	0	0
RELA/p50	0.02	0.003	-10000	0	-10000	0	0
MAPK3	-0.01	0.043	0.2	3	-0.22	1	4
MAPK1	-0.01	0.043	0.21	3	-0.19	2	5
p50/RELA/I-kappa-B-alpha	0.029	0.006	-10000	0	-10000	0	0
FADD	-0.008	0.094	0.2	3	-0.33	12	15
KSR1	-0.006	0.044	0.17	5	-0.16	4	9
MAPK8	-0.014	0.037	0.14	3	-0.2	1	4
TRAF2	0.02	0.003	-10000	0	-10000	0	0
response to radiation	0	0	0.002	3	-10000	0	3
CHUK	-0.017	0.093	0.2	2	-0.4	7	9
TNF R/SODD	0.027	0.01	-10000	0	-10000	0	0
TNF	0.023	0.032	0.29	4	-10000	0	4
CYCS	-0.003	0.047	0.16	6	-0.17	3	9
IKBKG	-0.012	0.1	0.24	5	-0.4	7	12
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.009	0.1	0.25	1	-0.32	17	18
RELA	0.02	0.003	-10000	0	-10000	0	0
RIPK1	0.02	0.005	-10000	0	-10000	0	0
AIFM1	-0.004	0.046	0.16	6	-0.17	3	9
TNF/TNF R/SODD	0.038	0.025	0.21	4	-10000	0	4
TNFRSF1A	0.019	0.005	-10000	0	-10000	0	0
response to heat	0	0	0.002	3	-10000	0	3
CASP8	-0.016	0.16	-10000	0	-0.57	18	18
NSMAF	-0.008	0.1	0.21	12	-0.31	16	28
response to hydrogen peroxide	0	0	0.002	5	-0.002	1	6
BCL2	0.014	0.04	-10000	0	-0.29	5	5

×

TCGA08_rtk_signaling

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
PDGFRA	-0.046	0.13	-10000	0	-0.29	62	62
HRAS	0.02	0.005	-10000	0	-10000	0	0
EGFR	0.018	0.026	-10000	0	-0.29	2	2
AKT	0.024	0.089	0.25	8	-0.23	10	18
FOXO3	0.02	0.004	-10000	0	-10000	0	0
AKT1	0.02	0.004	-10000	0	-10000	0	0
FOXO1	0.017	0.026	-10000	0	-0.29	2	2
AKT3	0.004	0.066	-10000	0	-0.29	14	14
FOXO4	0.02	0.002	-10000	0	-10000	0	0
MET	0.02	0.004	-10000	0	-10000	0	0
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
PIK3CB	0.015	0.009	-10000	0	-10000	0	0
NRAS	0.021	0.002	-10000	0	-10000	0	0
PIK3CG	0.019	0.019	-10000	0	-0.29	1	1
PIK3R3	0.02	0.002	-10000	0	-10000	0	0
PIK3R2	0.02	0.003	-10000	0	-10000	0	0
NF1	0.02	0.004	-10000	0	-10000	0	0
RAS	-0.009	0.054	0.22	1	-0.12	49	50
ERBB2	0.019	0.005	-10000	0	-10000	0	0
proliferation/survival/translation	-0.049	0.089	0.26	7	-0.22	8	15
PI3K	0.022	0.069	0.23	10	-0.15	2	12
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
KRAS	0.019	0.005	-10000	0	-10000	0	0
FOXO	0.047	0.06	0.24	8	-10000	0	8
AKT2	0.02	0.005	-10000	0	-10000	0	0
PTEN	0.019	0.005	-10000	0	-10000	0	0

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	0.032	0.053	0.31	9	-10000	0	9
NFATC2	0.068	0.058	0.37	1	-10000	0	1
NFATC3	0.034	0.031	-10000	0	-0.29	1	1
CD40LG	0.1	0.12	0.4	5	-0.53	1	6
ITCH	0.022	0.052	-10000	0	-10000	0	0
CBLB	0.02	0.05	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	0.062	0.11	0.43	10	-10000	0	10
JUNB	0.02	0.004	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0.062	0.068	0.17	82	-10000	0	82
T cell anergy	0.047	0.077	0.22	15	-10000	0	15
TLE4	0.029	0.055	-10000	0	-0.52	1	1
Jun/NFAT1-c-4/p21SNFT	0.13	0.12	0.49	2	-0.55	2	4
AP-1/NFAT1-c-4	0.19	0.19	0.6	10	-0.58	1	11
IKZF1	0.031	0.045	-10000	0	-10000	0	0
T-helper 2 cell differentiation	0.03	0.11	-10000	0	-10000	0	0
AP-1/NFAT1	0.088	0.1	0.31	10	-0.29	2	12
CALM1	0.041	0.032	-10000	0	-10000	0	0
EGR2	0.041	0.089	-10000	0	-0.73	2	2
EGR3	0.04	0.074	-10000	0	-0.56	1	1
NFAT1/FOXP3	0.068	0.085	0.37	11	-10000	0	11
EGR1	0.012	0.051	-10000	0	-0.29	8	8
JUN	0.032	0.023	-10000	0	-0.29	1	1
EGR4	0.028	0.045	0.29	8	-10000	0	8
mol:Ca2+	0.022	0.031	-10000	0	-10000	0	0
GBP3	0.031	0.045	-10000	0	-10000	0	0
FOSL1	0.039	0.069	0.29	20	-10000	0	20
NFAT1-c-4/MAF/IRF4	0.095	0.099	-10000	0	-0.64	1	1
DGKA	0.031	0.045	-10000	0	-10000	0	0
CREM	0.02	0.004	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	0.08	0.11	-10000	0	-0.67	1	1
CTLA4	0.03	0.072	0.38	8	-10000	0	8
NFAT1-c-4 (dimer)/EGR1	0.091	0.1	-10000	0	-0.67	1	1
NFAT1-c-4 (dimer)/EGR4	0.1	0.099	-10000	0	-0.67	1	1
FOS	0.016	0.074	-10000	0	-0.28	16	16
IFNG	0.068	0.12	0.37	3	-0.6	1	4
T cell activation	0.038	0.088	-10000	0	-10000	0	0
MAF	0.015	0.036	-10000	0	-0.29	4	4
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.043	0.074	0.65	2	-10000	0	2
TNF	0.053	0.089	0.38	1	-0.61	1	2
FASLG	0.06	0.097	-10000	0	-0.72	1	1
TBX21	0.037	0.041	-10000	0	-0.29	1	1
BATF3	0.019	0.005	-10000	0	-10000	0	0
PRKCQ	0.021	0.007	-10000	0	-10000	0	0
PTPN1	0.031	0.045	-10000	0	-10000	0	0
NFAT1-c-4/ICER1	0.095	0.094	-10000	0	-0.67	1	1
GATA3	0.045	0.08	0.29	27	-10000	0	27
T-helper 1 cell differentiation	0.069	0.12	0.37	3	-0.59	1	4
IL2RA	0.074	0.12	0.47	8	-10000	0	8
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	0.03	0.044	-10000	0	-10000	0	0
E2F1	0.025	0.04	0.3	6	-10000	0	6
PPARG	0	0.075	-10000	0	-0.29	18	18
SLC3A2	0.031	0.045	-10000	0	-10000	0	0
IRF4	0.019	0.025	0.29	1	-0.29	1	2
PTGS2	0.1	0.13	0.42	16	-0.53	1	17
CSF2	0.1	0.13	0.44	10	-0.53	1	11
JunB/Fra1/NFAT1-c-4	0.11	0.11	0.42	2	-0.64	1	3
IL4	0.03	0.11	-10000	0	-10000	0	0
IL5	0.095	0.12	0.41	4	-0.53	1	5
IL2	0.038	0.089	-10000	0	-10000	0	0
IL3	0.014	0.057	-10000	0	-0.41	4	4
RNF128	0.07	0.13	0.27	83	-10000	0	83
NFATC1	0.043	0.074	-10000	0	-0.66	2	2
CDK4	-0.029	0.06	-10000	0	-10000	0	0
PTPRK	0.031	0.045	-10000	0	-10000	0	0
IL8	0.19	0.18	0.41	54	-0.48	1	55
POU2F1	0.019	0.005	-10000	0	-10000	0	0

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.019	0.008	-10000	0	-10000	0	0
HSPA8	0.017	0.008	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.03	0.11	-10000	0	-0.19	84	84
AKT1	0.021	0.005	-10000	0	-10000	0	0
GSC	0	0.083	0.4	1	-0.43	3	4
NKX2-5	-0.003	0.013	-10000	0	-10000	0	0
muscle cell differentiation	0.005	0.1	0.42	7	-10000	0	7
SMAD2-3/SMAD4/SP1	0.035	0.06	-10000	0	-10000	0	0
SMAD4	0.013	0.028	-10000	0	-10000	0	0
CBFB	0.02	0.004	-10000	0	-10000	0	0
SAP18	0.02	0.004	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.038	0.021	0.21	2	-10000	0	2
SMAD3/SMAD4/VDR	0.044	0.043	-10000	0	-10000	0	0
MYC	0.014	0.037	-10000	0	-0.29	4	4
CDKN2B	-0.008	0.082	-10000	0	-0.51	4	4
AP1	0.005	0.052	-10000	0	-0.31	1	1
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.012	0.064	-10000	0	-0.28	5	5
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.004	0.047	-10000	0	-0.22	4	4
SP3	0.02	0.003	-10000	0	-10000	0	0
CREB1	0.019	0.006	-10000	0	-10000	0	0
FOXH1	0.028	0.065	0.29	15	-10000	0	15
SMAD3/SMAD4/GR	0.03	0.035	-10000	0	-10000	0	0
GATA3	0.046	0.08	0.3	27	-10000	0	27
SKI/SIN3/HDAC complex/NCoR1	-0.005	0.049	-10000	0	-0.31	2	2
MEF2C/TIF2	-0.03	0.08	0.19	7	-0.3	18	25
endothelial cell migration	0.004	0.12	0.54	11	-10000	0	11
MAX	0.02	0.004	-10000	0	-10000	0	0
RBBP7	0.02	0.004	-10000	0	-10000	0	0
RBBP4	0.021	0.001	-10000	0	-10000	0	0
RUNX2	0.02	0.004	-10000	0	-10000	0	0
RUNX3	0.021	0.016	0.29	1	-10000	0	1
RUNX1	0.02	0.004	-10000	0	-10000	0	0
CTBP1	0.019	0.006	-10000	0	-10000	0	0
NR3C1	0.02	0.005	-10000	0	-10000	0	0
VDR	0.02	0.003	-10000	0	-10000	0	0
CDKN1A	-0.006	0.052	-10000	0	-10000	0	0
KAT2B	0.019	0.006	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	0.036	0.058	0.22	10	-10000	0	10
DCP1A	0.019	0.006	-10000	0	-10000	0	0
SKI	0.02	0.004	-10000	0	-10000	0	0
SERPINE1	-0.004	0.12	-10000	0	-0.55	11	11
SMAD3/SMAD4/ATF2	0.031	0.035	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	0.029	0.035	-10000	0	-10000	0	0
SAP30	0.02	0.004	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.035	0.018	-10000	0	-10000	0	0
JUN	-0.023	0.045	-10000	0	-0.31	1	1
SMAD3/SMAD4/IRF7	0.031	0.035	-10000	0	-10000	0	0
TFE3	0.021	0.006	-10000	0	-10000	0	0
COL1A2	-0.006	0.17	-10000	0	-0.57	21	21
mesenchymal cell differentiation	-0.029	0.035	-10000	0	-10000	0	0
DLX1	0.054	0.099	0.29	42	-10000	0	42
TCF3	0.019	0.005	-10000	0	-10000	0	0
FOS	0.015	0.017	-10000	0	-10000	0	0
SMAD3/SMAD4/Max	0.03	0.035	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.038	0.014	-10000	0	-10000	0	0
ZBTB17	0.019	0.007	-10000	0	-10000	0	0
LAMC1	-0.016	0.03	0.19	3	-10000	0	3
TGIF2/HDAC complex/SMAD3/SMAD4	0.029	0.035	-10000	0	-10000	0	0
IRF7	0.02	0.005	-10000	0	-10000	0	0
ESR1	-0.075	0.15	-10000	0	-0.29	92	92
HNF4A	0.013	0.05	0.29	5	-0.29	3	8
MEF2C	-0.022	0.09	0.18	16	-0.3	19	35
SMAD2-3/SMAD4	0.03	0.041	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.037	0.016	-10000	0	-10000	0	0
IGHV3OR16-13	-0.022	0.094	-10000	0	-0.36	21	21
TGIF2/HDAC complex	0.019	0.005	-10000	0	-10000	0	0
CREBBP	0.019	0.008	-10000	0	-10000	0	0
SKIL	0.013	0.01	-10000	0	-10000	0	0
HDAC1	0.021	0.001	-10000	0	-10000	0	0
HDAC2	0.02	0.003	-10000	0	-10000	0	0
SNIP1	0.021	0.002	-10000	0	-10000	0	0
GCN5L2	0	0.002	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.034	0.035	-10000	0	-10000	0	0
MSG1/HSC70	0.027	0.02	0.22	2	-10000	0	2
SMAD2	0.016	0.02	-10000	0	-10000	0	0
SMAD3	0.015	0.024	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.003	0.033	-10000	0	-0.2	1	1
SMAD2/SMAD2/SMAD4	-0.01	0.06	-10000	0	-0.26	7	7
NCOR1	0.019	0.006	-10000	0	-10000	0	0
NCOA2	0.015	0.036	-10000	0	-0.29	4	4
NCOA1	0.02	0.004	-10000	0	-10000	0	0
MYOD/E2A	0.025	0.009	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.041	0.063	-10000	0	-10000	0	0
IFNB1	-0.019	0.022	-10000	0	-10000	0	0
SMAD3/SMAD4/MEF2C	0.014	0.095	0.23	1	-0.3	19	20
CITED1	0.022	0.023	0.29	2	-10000	0	2
SMAD2-3/SMAD4/ARC105	0.038	0.045	-10000	0	-10000	0	0
RBL1	0.019	0.006	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.002	0.046	-10000	0	-10000	0	0
RUNX1-3/PEBPB2	0.039	0.015	0.21	1	-10000	0	1
SMAD7	-0.008	0.064	-10000	0	-10000	0	0
MYC/MIZ-1	0.023	0.03	-10000	0	-0.2	4	4
SMAD3/SMAD4	-0.001	0.058	-10000	0	-0.49	2	2
IL10	-0.009	0.043	0.31	2	-10000	0	2
PIASy/HDAC complex	0.02	0.005	-10000	0	-10000	0	0
PIAS3	0.019	0.008	-10000	0	-10000	0	0
CDK2	0.02	0.007	-10000	0	-10000	0	0
IL5	-0.011	0.04	0.34	1	-10000	0	1
CDK4	0.02	0.007	-10000	0	-10000	0	0
PIAS4	0.02	0.005	-10000	0	-10000	0	0
ATF3	0.019	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4/SP1	0.027	0.054	-10000	0	-0.2	2	2
FOXG1	0.008	0.071	0.29	16	-10000	0	16
FOXO3	-0.016	0.007	-10000	0	-10000	0	0
FOXO1	-0.017	0.017	-10000	0	-0.2	2	2
FOXO4	-0.017	0.007	-10000	0	-10000	0	0
heart looping	-0.021	0.089	0.18	16	-0.3	19	35
CEBPB	0.019	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	0.056	0.069	0.22	30	-10000	0	30
MYOD1	-0.017	0.004	-10000	0	-10000	0	0
SMAD3/SMAD4/HNF4	0.029	0.044	0.22	3	-0.19	2	5
SMAD3/SMAD4/GATA3	0.045	0.06	0.24	1	-10000	0	1
SnoN/SIN3/HDAC complex/NCoR1	0.013	0.01	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.047	0.043	-10000	0	-10000	0	0
SMAD3/SMAD4/SP1-3	0.037	0.055	-10000	0	-10000	0	0
MED15	0.02	0.003	-10000	0	-10000	0	0
SP1	0.013	0.034	-10000	0	-0.14	4	4
SIN3B	0.02	0.003	-10000	0	-10000	0	0
SIN3A	0.02	0.004	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.031	0.068	0.21	10	-0.19	15	25
ITGB5	-0.019	0.038	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.001	0.042	-10000	0	-0.26	1	1
SMAD3/SMAD4/AR	-0.064	0.11	-10000	0	-0.19	126	126
AR	-0.12	0.15	-10000	0	-0.29	132	132
negative regulation of cell growth	0.002	0.049	-10000	0	-0.26	1	1
SMAD3/SMAD4/MYOD	0.028	0.035	-10000	0	-10000	0	0
E2F5	0.019	0.019	-10000	0	-0.29	1	1
E2F4	0.02	0.004	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.048	0.06	0.24	1	-10000	0	1
SMAD2-3/SMAD4/FOXO1-3a-4	0	0.033	-10000	0	-10000	0	0
TFDP1	0.02	0.004	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.025	0.061	-10000	0	-0.31	1	1
SMAD3/SMAD4/RUNX2	0.03	0.035	-10000	0	-10000	0	0
TGIF2	0.019	0.005	-10000	0	-10000	0	0
TGIF1	0.02	0.004	-10000	0	-10000	0	0
ATF2	0.02	0.003	-10000	0	-10000	0	0

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.033	0.054	0.17	6	-10000	0	6
NF kappa B1 p50/RelA/I kappa B alpha	-0.031	0.061	0.33	1	-10000	0	1
alphaV/beta3 Integrin/Osteopontin/Src	0.034	0.037	0.22	10	-10000	0	10
AP1	-0.058	0.08	-10000	0	-0.31	9	9
ILK	-0.028	0.058	0.23	1	-10000	0	1
bone resorption	-0.037	0.064	0.29	3	-0.26	1	4
PTK2B	0.019	0.006	-10000	0	-10000	0	0
PYK2/p130Cas	0.025	0.073	0.3	1	-10000	0	1
ITGAV	0.018	0.01	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.027	0.021	-10000	0	-0.2	2	2
alphaV/beta3 Integrin/Osteopontin	0.02	0.077	0.21	9	-0.17	33	42
MAP3K1	-0.029	0.058	0.18	7	-0.19	5	12
JUN	0.017	0.021	-10000	0	-0.29	1	1
MAPK3	-0.034	0.053	0.17	6	-10000	0	6
MAPK1	-0.034	0.053	0.17	6	-10000	0	6
Rac1/GDP	0.015	0.002	-10000	0	-10000	0	0
NFKB1	0.02	0.003	-10000	0	-10000	0	0
MAPK8	-0.033	0.056	0.18	7	-0.2	5	12
ITGB3	-0.017	0.1	-10000	0	-0.29	34	34
NFKBIA	-0.028	0.053	-10000	0	-10000	0	0
FOS	-0.005	0.082	-10000	0	-0.29	22	22
CD44	0.02	0.004	-10000	0	-10000	0	0
CHUK	0.02	0.003	-10000	0	-10000	0	0
PLAU	-0.028	0.065	0.4	1	-10000	0	1
NF kappa B1 p50/RelA	-0.044	0.055	-10000	0	-10000	0	0
BCAR1	0.02	0.004	-10000	0	-10000	0	0
RELA	0.02	0.003	-10000	0	-10000	0	0
alphaV beta3 Integrin	0.002	0.074	-10000	0	-0.2	33	33
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	-0.031	0.056	0.17	7	-10000	0	7
VAV3	-0.036	0.049	0.17	4	-10000	0	4
MAP3K14	-0.031	0.056	0.17	6	-10000	0	6
ROCK2	0.018	0.026	-10000	0	-0.29	2	2
SPP1	0.028	0.051	0.3	10	-10000	0	10
RAC1	0.02	0.003	-10000	0	-10000	0	0
Rac1/GTP	-0.036	0.046	0.16	4	-10000	0	4
MMP2	-0.057	0.093	0.27	1	-0.36	15	16

×

Visual signal transduction: Rods

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
mol:K +	0.02	0.003	-10000	0	-10000	0	0
GNAT1/GTP	0.012	0.003	-10000	0	-10000	0	0
Metarhodopsin II/Arrestin	0.017	0.011	-10000	0	-10000	0	0
PDE6G/GNAT1/GTP	0.023	0.013	0.19	1	-10000	0	1
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	-0.016	0.005	-10000	0	-10000	0	0
GRK1	-0.017	0.003	-10000	0	-10000	0	0
CNG Channel	0.05	0.049	0.24	2	-10000	0	2
mol:Na +	0.035	0.064	0.26	2	-10000	0	2
mol:ADP	-0.017	0.003	-10000	0	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.016	0.065	0.2	1	-0.17	30	31
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	0.059	0.067	0.3	3	-10000	0	3
CNGB1	0.086	0.12	0.29	72	-10000	0	72
RDH5	0.019	0.018	-10000	0	-0.29	1	1
SAG	-0.013	0.026	-10000	0	-0.29	2	2
mol:Ca2+	0.014	0.087	0.25	16	-10000	0	16
Na + (4 Units)	-0.001	0.057	0.11	47	-10000	0	47
RGS9	-0.016	0.098	-10000	0	-0.29	33	33
GNB1/GNGT1	0.026	0.007	-10000	0	-10000	0	0
GNAT1/GDP	0.019	0.059	-10000	0	-0.15	30	30
GUCY2D	0.016	0.02	0.29	1	-10000	0	1
GNGT1	-0.017	0.004	-10000	0	-10000	0	0
GUCY2F	-0.013	0.013	-10000	0	-10000	0	0
GNB5	0.02	0.005	-10000	0	-10000	0	0
mol:GMP (4 units)	-0.017	0.022	0.13	5	-10000	0	5
mol:11-cis-retinal	0.019	0.018	-10000	0	-0.29	1	1
mol:cGMP	0.03	0.031	0.2	6	-10000	0	6
GNB1	0.02	0.004	-10000	0	-10000	0	0
Rhodopsin	0.022	0.018	-10000	0	-0.2	1	1
SLC24A1	0.02	0.003	-10000	0	-10000	0	0
CNGA1	0.02	0.005	-10000	0	-10000	0	0
Metarhodopsin II	0.017	0.01	-10000	0	-10000	0	0
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.041	0.035	0.21	7	-10000	0	7
RGS9BP	0.02	0.017	0.29	1	-10000	0	1
Metarhodopsin II/Transducin	0.004	0.011	-10000	0	-0.17	1	1
GCAP Family/Ca ++	0.033	0.028	0.2	6	-10000	0	6
PDE6A/B	0.03	0.026	0.22	5	-10000	0	5
mol:Pi	0.016	0.065	0.2	1	-0.17	30	31
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	0.03	0.012	-10000	0	-10000	0	0
PDE6B	0.019	0.006	-10000	0	-10000	0	0
PDE6A	0.022	0.041	0.29	6	-10000	0	6
PDE6G	0.02	0.017	0.29	1	-10000	0	1
RHO	-0.003	0.016	-10000	0	-10000	0	0
PDE6	0.029	0.068	-10000	0	-0.15	26	26
GUCA1A	0.015	0.04	0.29	5	-10000	0	5
GC2/GCAP Family	0.042	0.031	0.21	6	-10000	0	6
GUCA1C	-0.007	0.028	0.29	2	-10000	0	2
GUCA1B	0.019	0.019	-10000	0	-0.29	1	1

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.018	0.007	-10000	0	-10000	0	0
NFATC1	0.02	0.083	0.27	8	-0.37	2	10
NFATC2	0.007	0.061	0.19	7	-0.3	3	10
NFATC3	0.009	0.005	-10000	0	-10000	0	0
YWHAE	0.019	0.006	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.003	0.061	0.18	6	-0.23	2	8
Exportin 1/Ran/NUP214	0.04	0.008	-10000	0	-10000	0	0
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	0.02	0.057	-10000	0	-0.21	2	2
BCL2/BAX	0.024	0.031	-10000	0	-0.2	5	5
CaM/Ca2+/Calcineurin A alpha-beta B1	0.014	0.007	-10000	0	-10000	0	0
CaM/Ca2+	0.014	0.006	-10000	0	-10000	0	0
BAX	0.02	0.004	-10000	0	-10000	0	0
MAPK14	0.019	0.007	-10000	0	-10000	0	0
BAD	0.02	0.003	-10000	0	-10000	0	0
CABIN1/MEF2D	0.012	0.058	0.18	2	-0.23	2	4
Calcineurin A alpha-beta B1/BCL2	0.014	0.04	-10000	0	-0.29	5	5
FKBP8	0.02	0.003	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.012	0.057	0.23	2	-0.18	2	4
KPNB1	0.021	0.002	-10000	0	-10000	0	0
KPNA2	0.02	0.004	-10000	0	-10000	0	0
XPO1	0.02	0.003	-10000	0	-10000	0	0
SFN	0.28	0.067	0.29	274	-10000	0	274
MAP3K8	0.019	0.007	-10000	0	-10000	0	0
NFAT4/CK1 alpha	-0.021	0.009	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	0.025	0.067	-10000	0	-0.25	5	5
CABIN1	0.003	0.061	0.18	6	-0.24	2	8
CALM1	0.019	0.008	-10000	0	-10000	0	0
RAN	0.02	0.002	-10000	0	-10000	0	0
MAP3K1	0.02	0.005	-10000	0	-10000	0	0
CAMK4	0.019	0.006	-10000	0	-10000	0	0
mol:Ca2+	0	0.002	-10000	0	-10000	0	0
MAPK3	0.02	0.002	-10000	0	-10000	0	0
YWHAH	0.02	0.003	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.029	0.007	-10000	0	-10000	0	0
YWHAB	0.019	0.006	-10000	0	-10000	0	0
MAPK8	0.017	0.026	-10000	0	-0.29	2	2
MAPK9	0.02	0.004	-10000	0	-10000	0	0
YWHAG	0.02	0.004	-10000	0	-10000	0	0
FKBP1A	0.019	0.005	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.018	0.081	0.3	3	-0.37	4	7
PRKCH	0.02	0.003	-10000	0	-10000	0	0
CABIN1/Cbp/p300	0.027	0.013	-10000	0	-10000	0	0
CASP3	0.019	0.008	-10000	0	-10000	0	0
PIM1	0.02	0.003	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.013	0.005	-10000	0	-10000	0	0
apoptosis	0.009	0.021	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.059	0.048	-10000	0	-10000	0	0
PRKCB	0.018	0.026	-10000	0	-0.29	2	2
PRKCE	0.02	0.004	-10000	0	-10000	0	0
JNK2/NFAT4	0.016	0.037	-10000	0	-0.17	2	2
BAD/BCL-XL	0.026	0.011	-10000	0	-10000	0	0
PRKCD	0.019	0.006	-10000	0	-10000	0	0
NUP214	0.02	0.002	-10000	0	-10000	0	0
PRKCZ	0.019	0.007	-10000	0	-10000	0	0
PRKCA	0.014	0.044	-10000	0	-0.29	6	6
PRKCG	0.03	0.077	0.29	22	-10000	0	22
PRKCQ	0.02	0.003	-10000	0	-10000	0	0
FKBP38/BCL2	0.025	0.028	-10000	0	-0.2	4	4
EP300	0.019	0.008	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.019	0.005	-10000	0	-10000	0	0
NFATc/JNK1	0.028	0.08	0.31	4	-0.36	2	6
CaM/Ca2+/FKBP38	0.025	0.011	-10000	0	-10000	0	0
FKBP12/FK506	0.014	0.004	-10000	0	-10000	0	0
CSNK1A1	-0.014	0.005	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0.024	0.011	-10000	0	-10000	0	0
NFATc/ERK1	0.029	0.08	0.28	4	-0.36	2	6
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	0.019	0.058	-10000	0	-0.21	2	2
NR4A1	0.001	0.081	0.26	4	-0.33	6	10
GSK3B	0.016	0.01	-10000	0	-10000	0	0
positive T cell selection	0.009	0.005	-10000	0	-10000	0	0
NFAT1/CK1 alpha	0.005	0.042	0.11	2	-0.24	3	5
RCH1/ KPNB1	0.03	0.005	-10000	0	-10000	0	0
YWHAQ	0.02	0.004	-10000	0	-10000	0	0
PRKACA	0.019	0.007	-10000	0	-10000	0	0
AKAP5	0.02	0.003	-10000	0	-10000	0	0
MEF2D	0.018	0.008	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.02	0.005	-10000	0	-10000	0	0
NFATc/p38 alpha	0.028	0.078	0.27	5	-0.36	2	7
CREBBP	0.019	0.008	-10000	0	-10000	0	0
BCL2	0.014	0.04	-10000	0	-0.29	5	5

×

FoxO family signaling

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
G6PC	-0.007	0.044	-10000	0	-10000	0	0
PLK1	0.083	0.15	0.46	2	-10000	0	2
CDKN1B	0.042	0.096	-10000	0	-0.33	3	3
FOXO3	0.069	0.11	-10000	0	-10000	0	0
KAT2B	0.03	0.019	-10000	0	-10000	0	0
FOXO1/SIRT1	0.005	0.041	-10000	0	-10000	0	0
CAT	0.054	0.11	0.41	1	-10000	0	1
CTNNB1	0.019	0.006	-10000	0	-10000	0	0
AKT1	0.031	0.019	-10000	0	-10000	0	0
FOXO1	-0.002	0.043	-10000	0	-10000	0	0
MAPK10	-0.003	0.019	0.18	1	-0.16	1	2
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	-0.027	0.064	-10000	0	-10000	0	0
response to oxidative stress	0.012	0.016	-10000	0	-10000	0	0
FOXO3A/SIRT1	0.06	0.11	-10000	0	-0.38	2	2
XPO1	0.02	0.003	-10000	0	-10000	0	0
EP300	0.02	0.003	-10000	0	-10000	0	0
BCL2L11	0.024	0.078	-10000	0	-0.7	3	3
FOXO1/SKP2	0.007	0.038	-10000	0	-10000	0	0
mol:GDP	0.012	0.016	-10000	0	-10000	0	0
RAN	0.021	0.002	-10000	0	-10000	0	0
GADD45A	0.033	0.088	-10000	0	-10000	0	0
YWHAQ	0.02	0.004	-10000	0	-10000	0	0
FOXO1/14-3-3 family	0.041	0.09	0.22	2	-0.33	5	7
MST1	0.03	0.02	-10000	0	-10000	0	0
CSNK1D	0.02	0.004	-10000	0	-10000	0	0
CSNK1E	0.02	0.003	-10000	0	-10000	0	0
FOXO4/14-3-3 family	0.066	0.071	0.24	1	-0.32	2	3
YWHAB	0.019	0.006	-10000	0	-10000	0	0
MAPK8	-0.003	0.022	0.18	2	-10000	0	2
MAPK9	-0.003	0.022	0.18	2	-10000	0	2
YWHAG	0.02	0.004	-10000	0	-10000	0	0
YWHAE	0.019	0.006	-10000	0	-10000	0	0
YWHAZ	0.02	0.005	-10000	0	-10000	0	0
SIRT1	0.008	0.019	-10000	0	-10000	0	0
SOD2	0.024	0.096	-10000	0	-10000	0	0
RBL2	0.025	0.17	-10000	0	-0.65	11	11
RAL/GDP	0.036	0.014	-10000	0	-10000	0	0
CHUK	0.031	0.019	-10000	0	-10000	0	0
Ran/GTP	0.016	0.002	-10000	0	-10000	0	0
CSNK1G2	0.019	0.005	-10000	0	-10000	0	0
RAL/GTP	0.035	0.013	-10000	0	-10000	0	0
CSNK1G1	0.02	0.003	-10000	0	-10000	0	0
FASLG	0.032	0.036	-10000	0	-10000	0	0
SKP2	0.018	0.007	-10000	0	-10000	0	0
USP7	0.02	0.005	-10000	0	-10000	0	0
IKBKB	0.03	0.019	-10000	0	-10000	0	0
CCNB1	0.052	0.11	-10000	0	-10000	0	0
FOXO1-3a-4/beta catenin	0.031	0.08	0.3	2	-10000	0	2
proteasomal ubiquitin-dependent protein catabolic process	0.007	0.038	-10000	0	-10000	0	0
CSNK1A1	0.02	0.004	-10000	0	-10000	0	0
SGK1	0.031	0.019	-10000	0	-10000	0	0
CSNK1G3	0.02	0.004	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.028	0.005	-10000	0	-10000	0	0
ZFAND5	-0.025	0.06	-10000	0	-10000	0	0
SFN	0.28	0.067	0.29	274	-10000	0	274
CDK2	0.019	0.005	-10000	0	-10000	0	0
FOXO3A/14-3-3	0.073	0.066	0.22	2	-10000	0	2
CREBBP	0.019	0.006	-10000	0	-10000	0	0
FBXO32	0.053	0.18	0.46	3	-0.98	5	8
BCL6	0.037	0.093	-10000	0	-10000	0	0
RALB	0.021	0.002	-10000	0	-10000	0	0
RALA	0.021	0.002	-10000	0	-10000	0	0
YWHAH	0.02	0.003	-10000	0	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	0.026	0.007	-10000	0	-10000	0	0
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0.02	0.005	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.021	0.016	0.29	1	-10000	0	1
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.019	0.006	-10000	0	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.003	0.011	-10000	0	-0.17	1	1
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.02	0.005	-10000	0	-10000	0	0
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	0.02	0.004	-10000	0	-10000	0	0
FYN	0.015	0.04	-10000	0	-0.29	5	5
MAP3K12	0.019	0.018	-10000	0	-0.29	1	1
FGR	0.02	0.002	-10000	0	-10000	0	0
p38 alpha/TAB1	-0.025	0.062	-10000	0	-0.26	12	12
PRKG1	-0.055	0.13	-10000	0	-0.29	68	68
DUSP8	0.019	0.019	-10000	0	-0.29	1	1
PGK/cGMP/p38 alpha	-0.018	0.098	-10000	0	-0.28	18	18
apoptosis	-0.024	0.06	-10000	0	-0.26	12	12
RAL/GTP	0.028	0.004	-10000	0	-10000	0	0
LYN	0.02	0.004	-10000	0	-10000	0	0
DUSP1	0.014	0.04	-10000	0	-0.29	5	5
PAK1	0.019	0.005	-10000	0	-10000	0	0
SRC	0.019	0.006	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.048	0.016	-10000	0	-10000	0	0
TRAF6	0.02	0.004	-10000	0	-10000	0	0
RAC1	0.02	0.003	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
mol:cGMP	0	0	-10000	0	-10000	0	0
CCM2	0.02	0.002	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0.027	0.006	-10000	0	-10000	0	0
MAPK11	0.016	0.079	0.21	5	-0.27	4	9
BLK	0.064	0.11	0.29	52	-10000	0	52
HCK	0.019	0.006	-10000	0	-10000	0	0
MAP2K3	0.02	0.005	-10000	0	-10000	0	0
DUSP16	0.02	0.005	-10000	0	-10000	0	0
DUSP10	0.019	0.005	-10000	0	-10000	0	0
TRAF6/MEKK3	0.025	0.007	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.007	0.088	0.2	3	-0.29	11	14
positive regulation of innate immune response	0.014	0.094	0.23	6	-0.31	7	13
LCK	0.021	0.001	-10000	0	-10000	0	0
p38alpha-beta/MKP7	0.022	0.093	0.27	2	-0.32	5	7
p38alpha-beta/MKP5	0.019	0.093	0.24	2	-0.32	6	8
PGK/cGMP	-0.034	0.089	-10000	0	-0.2	68	68
PAK2	0.013	0.01	-10000	0	-10000	0	0
p38alpha-beta/MKP1	0.02	0.096	0.26	3	-0.32	7	10
CDC42	0.02	0.003	-10000	0	-10000	0	0
RALB	0.021	0.002	-10000	0	-10000	0	0
RALA	0.02	0.002	-10000	0	-10000	0	0
PAK3	0.004	0.025	0.29	1	-10000	0	1

×

Caspase cascade in apoptosis

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
TOP1	0.002	0.079	0.24	1	-0.38	7	8
ACTA1	-0.003	0.069	0.22	4	-0.34	2	6
NUMA1	-0.005	0.092	0.24	1	-0.44	7	8
SPTAN1	-0.009	0.067	0.23	4	-0.34	2	6
LIMK1	-0.006	0.07	0.24	5	-0.32	2	7
BIRC3	0.017	0.018	0.29	1	-10000	0	1
BIRC2	0.016	0.008	-10000	0	-10000	0	0
BAX	0.02	0.004	-10000	0	-10000	0	0
CASP10	-0.012	0.027	-10000	0	-10000	0	0
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.02	0.002	-10000	0	-10000	0	0
PTK2	0.001	0.08	0.24	1	-0.38	7	8
DIABLO	0.021	0.001	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.008	0.067	0.23	4	-0.33	2	6
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.021	0.001	-10000	0	-10000	0	0
GSN	-0.009	0.067	0.23	4	-0.34	2	6
MADD	0.02	0.004	-10000	0	-10000	0	0
TFAP2A	0.12	0.14	0.34	3	-0.51	9	12
BID	0	0.015	-10000	0	-10000	0	0
MAP3K1	-0.01	0.092	-10000	0	-0.4	13	13
TRADD	0.02	0.004	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.03	0.005	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.006	0.07	0.24	5	-0.34	2	7
CASP9	0.02	0.003	-10000	0	-10000	0	0
DNA repair	-0.001	0.052	0.36	1	-0.16	1	2
neuron apoptosis	-0.011	0.13	-10000	0	-0.68	9	9
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.01	0.086	0.24	1	-0.42	6	7
APAF1	0.02	0.001	-10000	0	-10000	0	0
CASP6	-0.004	0.13	-10000	0	-0.89	6	6
TRAF2	0.02	0.003	-10000	0	-10000	0	0
ICAD/CAD	-0.013	0.064	0.29	2	-0.31	2	4
CASP7	-0.019	0.1	-10000	0	-0.32	11	11
KRT18	0.037	0.077	-10000	0	-0.51	2	2
apoptosis	-0.017	0.091	0.22	1	-0.43	7	8
DFFA	-0.009	0.064	0.21	2	-0.33	2	4
DFFB	-0.009	0.064	0.2	3	-0.33	2	5
PARP1	0.001	0.053	0.16	1	-0.36	1	2
actin filament polymerization	0.01	0.073	0.3	2	-0.27	5	7
TNF	0.023	0.032	0.29	4	-10000	0	4
CYCS	0.003	0.032	0.16	5	-0.2	1	6
SATB1	-0.008	0.12	-10000	0	-0.83	6	6
SLK	-0.009	0.063	0.2	2	-0.33	2	4
p15 BID/BAX	0.009	0.032	0.2	1	-0.17	2	3
CASP2	-0.005	0.054	0.22	1	-0.24	5	6
JNK cascade	0.01	0.091	0.4	13	-10000	0	13
CASP3	-0.004	0.068	0.21	3	-0.35	2	5
LMNB2	-0.007	0.11	0.21	1	-0.39	13	14
RIPK1	0.02	0.005	-10000	0	-10000	0	0
CASP4	0.018	0.007	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	0.042	0.024	0.21	1	-10000	0	1
negative regulation of DNA binding	0.12	0.13	0.34	4	-0.51	9	13
stress fiber formation	-0.009	0.063	0.2	2	-0.32	2	4
GZMB	-0.006	0.042	0.14	23	-10000	0	23
CASP1	0.006	0.002	-10000	0	-10000	0	0
LMNB1	-0.007	0.11	0.21	1	-0.42	13	14
APP	-0.011	0.13	-10000	0	-0.69	9	9
TNFRSF1A	0.019	0.005	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	-0.009	0.002	-10000	0	-10000	0	0
VIM	-0.012	0.094	0.23	1	-0.48	6	7
LMNA	0.007	0.064	0.21	1	-0.29	6	7
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0	0.062	0.24	1	-0.19	16	17
LRDD	0	0	-10000	0	-10000	0	0
SREBF1	-0.008	0.063	0.2	2	-0.34	2	4
APAF-1/Caspase 9	0.005	0.085	-10000	0	-0.56	6	6
nuclear fragmentation during apoptosis	-0.005	0.09	0.24	1	-0.43	7	8
CFL2	-0.011	0.073	0.27	5	-0.31	2	7
GAS2	-0.01	0.063	0.21	2	-0.33	2	4
positive regulation of apoptosis	-0.002	0.1	0.22	1	-0.48	7	8
PRF1	0.02	0.003	-10000	0	-10000	0	0

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.033	0.014	-10000	0	-0.15	1	1
RGS9BP	0.02	0.017	0.29	1	-10000	0	1
mol:GTP	0	0	-10000	0	-10000	0	0
GRK1	-0.017	0.003	-10000	0	-10000	0	0
mol:Na +	0.024	0.006	-10000	0	-10000	0	0
mol:ADP	-0.013	0.019	0.26	1	-10000	0	1
GNAT2	0.011	0.016	-10000	0	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.016	0.065	0.2	1	-0.17	30	31
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.023	0.006	-10000	0	-10000	0	0
GRK7	0.011	0.013	-10000	0	-10000	0	0
CNGB3	0.006	0.018	-10000	0	-10000	0	0
Cone Metarhodopsin II/X-Arrestin	0.013	0.002	-10000	0	-10000	0	0
mol:Ca2+	-0.012	0.037	0.17	11	-10000	0	11
Cone PDE6	0.029	0.067	-10000	0	-0.15	30	30
Cone Metarhodopsin II	0.017	0.011	-10000	0	-10000	0	0
Na + (4 Units)	0.033	0.011	-10000	0	-10000	0	0
GNAT2/GDP	0.023	0.061	0.19	1	-0.15	30	31
GNB5	0.02	0.005	-10000	0	-10000	0	0
mol:GMP (4 units)	-0.016	0.027	0.17	6	-10000	0	6
Cone Transducin	0.036	0.015	-10000	0	-0.16	1	1
SLC24A2	0	0.019	-10000	0	-10000	0	0
GNB3/GNGT2	0.028	0.015	-10000	0	-0.2	1	1
GNB3	0.018	0.019	-10000	0	-0.29	1	1
GNAT2/GTP	0.015	0.002	-10000	0	-10000	0	0
CNGA3	0.003	0.019	-10000	0	-10000	0	0
ARR3	-0.008	0.016	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
cGMP/Cone CNG Channel	0.025	0.006	-10000	0	-10000	0	0
mol:Pi	0.016	0.065	0.2	1	-0.17	30	31
Cone CNG Channel	0.039	0.017	-10000	0	-10000	0	0
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	0	0.019	-10000	0	-10000	0	0
RGS9	-0.016	0.098	-10000	0	-0.29	33	33
PDE6C	-0.017	0.003	-10000	0	-10000	0	0
GNGT2	0.02	0.002	-10000	0	-10000	0	0
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	-0.016	0.004	-10000	0	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	-0.015	0.028	0.099	13	-10000	0	13
SNTA1	0.019	0.006	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	-0.015	0.028	0.099	13	-10000	0	13
MAPK12	-0.012	0.005	-10000	0	-10000	0	0
CCND1	-0.007	0.055	-10000	0	-0.34	8	8
p38 gamma/SNTA1	-0.011	0.029	0.18	4	-10000	0	4
MAP2K3	0.02	0.005	-10000	0	-10000	0	0
PKN1	0.02	0.004	-10000	0	-10000	0	0
G2/M transition checkpoint	-0.011	0.005	-10000	0	-10000	0	0
MAP2K6	-0.007	0.005	-10000	0	-10000	0	0
MAPT	-0.007	0.049	0.19	5	-0.23	7	12
MAPK13	-0.01	0.038	0.16	13	-10000	0	13
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.003	0.001	-10000	0	-10000	0	0

×

HIV-1 Nef: Negative effector of Fas and TNF-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.019	0.005	-10000	0	-10000	0	0
Caspase 8 (4 units)	0.016	0.046	-10000	0	-0.27	1	1
NEF	0.002	0.007	-10000	0	-10000	0	0
NFKBIA	0.021	0.007	-10000	0	-10000	0	0
BIRC3	-0.01	0.048	0.22	11	-10000	0	11
CYCS	-0.01	0.048	0.15	13	-0.18	3	16
RIPK1	0.02	0.005	-10000	0	-10000	0	0
CD247	0.021	0.009	-10000	0	-10000	0	0
MAP2K7	-0.008	0.14	-10000	0	-0.63	11	11
protein ubiquitination	-0.008	0.075	0.31	3	-0.36	4	7
CRADD	0.021	0.001	-10000	0	-10000	0	0
DAXX	0.02	0.004	-10000	0	-10000	0	0
FAS	0.02	0.004	-10000	0	-10000	0	0
BID	-0.002	0.047	0.16	13	-0.18	4	17
NF-kappa-B/RelA/I kappa B alpha	0.045	0.031	0.26	5	-10000	0	5
TRADD	0.02	0.004	-10000	0	-10000	0	0
MAP3K5	0.02	0.004	-10000	0	-10000	0	0
CFLAR	0.019	0.005	-10000	0	-10000	0	0
FADD	0.019	0.005	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.045	0.031	0.26	5	-10000	0	5
MAPK8	-0.012	0.13	-10000	0	-0.58	11	11
APAF1	0.021	0.001	-10000	0	-10000	0	0
TRAF1	0.021	0.002	-10000	0	-10000	0	0
TRAF2	0.02	0.003	-10000	0	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.002	0.034	-10000	0	-0.18	4	4
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	-0.006	0.081	0.21	1	-0.43	5	6
CHUK	-0.011	0.076	0.3	2	-0.4	4	6
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.048	0.027	-10000	0	-10000	0	0
TCRz/NEF	0.017	0.016	0.17	3	-10000	0	3
TNF	0.023	0.032	0.29	4	-10000	0	4
FASLG	-0.009	0.029	0.27	3	-10000	0	3
NFKB1	0.021	0.007	-10000	0	-10000	0	0
TNFR1A/BAG4/TNF-alpha	0.038	0.025	0.21	4	-10000	0	4
CASP6	-0.005	0.14	-10000	0	-0.47	21	21
CASP7	-0.015	0.096	0.26	5	-0.36	7	12
RELA	0.022	0.007	-10000	0	-10000	0	0
CASP2	0.02	0.005	-10000	0	-10000	0	0
CASP3	-0.019	0.099	0.26	6	-0.35	9	15
TNFRSF1A	0.019	0.005	-10000	0	-10000	0	0
TNFR1A/BAG4	0.027	0.01	-10000	0	-10000	0	0
CASP8	0.019	0.005	-10000	0	-10000	0	0
CASP9	0.02	0.003	-10000	0	-10000	0	0
MAP3K14	-0.008	0.078	0.19	2	-0.4	5	7
APAF-1/Caspase 9	-0.024	0.043	-10000	0	-0.21	1	1
BCL2	-0.016	0.12	-10000	0	-0.55	11	11

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.022	0.01	-10000	0	-10000	0	0
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	-0.018	0.083	0.47	1	-10000	0	1
IL27/IL27R/JAK1	0.059	0.083	-10000	0	-10000	0	0
TBX21	0.01	0.088	0.29	3	-10000	0	3
IL12B	0.026	0.035	0.31	4	-10000	0	4
IL12A	0.008	0.049	0.21	15	-10000	0	15
IL6ST	0.01	0.059	-10000	0	-0.3	10	10
IL27RA/JAK1	0.023	0.038	-10000	0	-10000	0	0
IL27	0.017	0.02	-10000	0	-10000	0	0
TYK2	0.026	0.015	-10000	0	-10000	0	0
T-helper cell lineage commitment	0.013	0.059	0.39	1	-10000	0	1
T-helper 2 cell differentiation	-0.018	0.083	0.47	1	-10000	0	1
T cell proliferation during immune response	-0.018	0.083	0.47	1	-10000	0	1
MAPKKK cascade	0.018	0.083	-10000	0	-0.47	1	1
STAT3	0.02	0.002	-10000	0	-10000	0	0
STAT2	0.02	0.003	-10000	0	-10000	0	0
STAT1	0.018	0.011	-10000	0	-10000	0	0
IL12RB1	0.022	0.005	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	0.031	0.12	0.3	20	-10000	0	20
IL27/IL27R/JAK2/TYK2	0.018	0.084	-10000	0	-0.48	1	1
positive regulation of T cell mediated cytotoxicity	0.018	0.083	-10000	0	-0.47	1	1
STAT1 (dimer)	0.062	0.12	-10000	0	-10000	0	0
JAK2	0.023	0.014	-10000	0	-10000	0	0
JAK1	0.018	0.011	-10000	0	-10000	0	0
STAT2 (dimer)	0.024	0.087	-10000	0	-0.46	1	1
T cell proliferation	0.012	0.081	0.3	1	-0.46	1	2
IL12/IL12R/TYK2/JAK2	0.019	0.18	-10000	0	-0.65	15	15
IL17A	0.013	0.052	-10000	0	-10000	0	0
mast cell activation	-0.018	0.083	0.47	1	-10000	0	1
IFNG	0.021	0.04	0.1	47	-0.1	2	49
T cell differentiation	0.001	0.004	0.012	16	-10000	0	16
STAT3 (dimer)	0.025	0.087	-10000	0	-0.46	1	1
STAT5A (dimer)	0.025	0.087	-10000	0	-0.46	1	1
STAT4 (dimer)	0.025	0.086	-10000	0	-0.46	1	1
STAT4	0.02	0.004	-10000	0	-10000	0	0
T cell activation	-0.003	0.002	-10000	0	-10000	0	0
IL27R/JAK2/TYK2	0.046	0.07	-10000	0	-10000	0	0
GATA3	0.002	0.072	0.65	1	-10000	0	1
IL18	-0.005	0.016	0.14	3	-10000	0	3
positive regulation of mast cell cytokine production	0.025	0.086	-10000	0	-0.45	1	1
IL27/EBI3	0.034	0.022	-10000	0	-10000	0	0
IL27RA	0.013	0.04	-10000	0	-10000	0	0
IL6	0.029	0.043	0.3	7	-10000	0	7
STAT5A	0.02	0.002	-10000	0	-10000	0	0
monocyte differentiation	0.001	0.002	-10000	0	-10000	0	0
IL2	-0.015	0.016	-10000	0	-10000	0	0
IL1B	0.019	0.059	0.14	52	-10000	0	52
EBI3	0.02	0.016	-10000	0	-10000	0	0
TNF	-0.003	0.028	0.18	6	-10000	0	6

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.024	0.032	0.29	4	-10000	0	4
mol:Halofuginone	0.001	0	-10000	0	-10000	0	0
ITGA1	0.02	0.005	-10000	0	-10000	0	0
CDKN1A	0.006	0.011	-10000	0	-10000	0	0
PRL-3/alpha Tubulin	0.028	0.009	-10000	0	-10000	0	0
mol:Ca2+	-0.049	0.07	-10000	0	-0.21	48	48
AGT	-0.039	0.12	-10000	0	-0.29	54	54
CCNA2	-0.021	0.022	-10000	0	-10000	0	0
TUBA1B	0.02	0.002	-10000	0	-10000	0	0
EGR1	-0.012	0.031	-10000	0	-0.19	8	8
CDK2/Cyclin E1	0.035	0.046	-10000	0	-0.29	3	3
MAPK3	-0.017	0.005	-10000	0	-10000	0	0
PRL-2 /Rab GGTase beta	0.03	0.003	-10000	0	-10000	0	0
MAPK1	-0.017	0.005	-10000	0	-10000	0	0
PTP4A1	-0.018	0.022	-10000	0	-10000	0	0
PTP4A3	0.019	0.005	-10000	0	-10000	0	0
PTP4A2	0.021	0.002	-10000	0	-10000	0	0
ITGB1	-0.017	0.006	-10000	0	-10000	0	0
SRC	0.019	0.006	-10000	0	-10000	0	0
RAC1	0.002	0.035	-10000	0	-0.32	3	3
Rab GGTase beta/Rab GGTase alpha	0.03	0.005	-10000	0	-10000	0	0
PRL-1/ATF-5	-0.01	0.052	-10000	0	-10000	0	0
RABGGTA	0.02	0.003	-10000	0	-10000	0	0
BCAR1	-0.02	0.007	-10000	0	-10000	0	0
RHOC	0.002	0.035	-10000	0	-0.32	3	3
RHOA	-0.011	0.071	-10000	0	-0.32	14	14
cell motility	0.007	0.06	-10000	0	-0.34	2	2
PRL-1/alpha Tubulin	-0.008	0.057	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	0.027	0.01	-10000	0	-10000	0	0
ROCK1	0.007	0.057	-10000	0	-0.34	2	2
RABGGTB	0.021	0.002	-10000	0	-10000	0	0
CDK2	0.02	0.002	-10000	0	-10000	0	0
mitosis	-0.018	0.022	-10000	0	-10000	0	0
ATF5	0.02	0.004	-10000	0	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

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
ERK1-2/ELK1	-0.004	0.1	-10000	0	-0.42	5	5
MAP3K8	0.017	0.012	-10000	0	-10000	0	0
FOS	-0.004	0.077	0.25	1	-0.4	4	5
PRKCA	0.01	0.046	-10000	0	-0.29	6	6
PTPN7	0.015	0.015	-10000	0	-10000	0	0
HRAS	0.017	0.011	-10000	0	-10000	0	0
PRKCB	0.015	0.029	-10000	0	-0.29	2	2
NRAS	0.018	0.011	-10000	0	-10000	0	0
RAS family/GTP	0.031	0.021	-10000	0	-10000	0	0
MAPK3	0.004	0.064	-10000	0	-0.63	2	2
MAP2K1	-0.013	0.076	-10000	0	-0.36	9	9
ELK1	0.016	0.016	-10000	0	-10000	0	0
BRAF	-0.003	0.049	-10000	0	-0.3	7	7
mol:GTP	0	0.001	-10000	0	-0.004	22	22
MAPK1	0.003	0.057	-10000	0	-0.42	3	3
RAF1	-0.006	0.062	-10000	0	-0.33	9	9
KRAS	0.017	0.011	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.049	0.015	-10000	0	-10000	0	0
HDAC3	0.02	0.004	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.018	0.006	-10000	0	-10000	0	0
GATA1/HDAC4	0.026	0.015	0.22	1	-10000	0	1
GATA1/HDAC5	0.03	0.012	0.22	1	-10000	0	1
GATA2/HDAC5	0.019	0.037	-10000	0	-0.2	7	7
HDAC5/BCL6/BCoR	0.026	0.02	-10000	0	-10000	0	0
HDAC9	0.009	0.059	-10000	0	-0.29	11	11
Glucocorticoid receptor/Hsp90/HDAC6	0.038	0.013	-10000	0	-10000	0	0
HDAC4/ANKRA2	0.026	0.011	-10000	0	-10000	0	0
HDAC5/YWHAB	0.028	0.009	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.005	0.002	-10000	0	-10000	0	0
GATA2	0.009	0.048	-10000	0	-0.29	7	7
HDAC4/RFXANK	0.026	0.011	-10000	0	-10000	0	0
BCOR	0.02	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.02	0.004	-10000	0	-10000	0	0
HDAC5	0.02	0.002	-10000	0	-10000	0	0
GNB1/GNG2	0.029	0.007	-10000	0	-10000	0	0
Histones	-0.013	0.062	-10000	0	-0.21	16	16
ADRBK1	0.02	0.003	-10000	0	-10000	0	0
HDAC4	0.018	0.007	-10000	0	-10000	0	0
XPO1	0.02	0.003	-10000	0	-10000	0	0
HDAC5/ANKRA2	0.029	0.007	-10000	0	-10000	0	0
HDAC4/Ubc9	0.026	0.011	-10000	0	-10000	0	0
HDAC7	0.02	0.003	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.028	0.009	-10000	0	-10000	0	0
TUBA1B	0.02	0.002	-10000	0	-10000	0	0
HDAC6	0.02	0.003	-10000	0	-10000	0	0
HDAC5/RFXANK	0.03	0.006	-10000	0	-10000	0	0
CAMK4	0.019	0.006	-10000	0	-10000	0	0
Tubulin/HDAC6	0.038	0.012	-10000	0	-10000	0	0
SUMO1	0.019	0.005	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.019	0.006	-10000	0	-10000	0	0
GATA1	0.012	0.023	0.29	1	-10000	0	1
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.019	0.006	-10000	0	-10000	0	0
NR3C1	0.02	0.004	-10000	0	-10000	0	0
SUMO1/HDAC4	0.021	0.031	-10000	0	-0.16	4	4
SRF	0.02	0.004	-10000	0	-10000	0	0
HDAC4/YWHAB	0.025	0.012	-10000	0	-10000	0	0
Tubulin	0.029	0.008	-10000	0	-10000	0	0
HDAC4/14-3-3 E	0.025	0.012	-10000	0	-10000	0	0
GNB1	0.02	0.004	-10000	0	-10000	0	0
RANGAP1	0.02	0.003	-10000	0	-10000	0	0
BCL6/BCoR	0.019	0.015	-10000	0	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0.036	0.015	-10000	0	-10000	0	0
HDAC4/SRF	0.035	0.016	-10000	0	-10000	0	0
HDAC4/ER alpha	-0.047	0.11	-10000	0	-0.2	94	94
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	-0.012	0.061	-10000	0	-0.2	16	16
cell motility	0.038	0.012	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.02	0.004	-10000	0	-10000	0	0
HDAC7/HDAC3	0.029	0.007	-10000	0	-10000	0	0
BCL6	0.013	0.01	-10000	0	-10000	0	0
HDAC4/CaMK II delta B	0.018	0.007	-10000	0	-10000	0	0
Hsp90/HDAC6	0.028	0.008	-10000	0	-10000	0	0
ESR1	-0.082	0.14	-10000	0	-0.29	95	95
HDAC6/HDAC11	0.028	0.009	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.018	0.039	-10000	0	-0.16	4	4
NPC	0.012	0.002	-10000	0	-10000	0	0
MEF2C	-0.003	0.08	-10000	0	-0.29	21	21
RAN	0.02	0.002	-10000	0	-10000	0	0
HDAC4/MEF2C	0.035	0.058	-10000	0	-0.16	20	20
GNG2	0.02	0.003	-10000	0	-10000	0	0
NCOR2	0.021	0.002	-10000	0	-10000	0	0
TUBB2A	0.019	0.005	-10000	0	-10000	0	0
HDAC11	0.019	0.005	-10000	0	-10000	0	0
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
RANBP2	0.02	0.003	-10000	0	-10000	0	0
ANKRA2	0.02	0.004	-10000	0	-10000	0	0
RFXANK	0.02	0.003	-10000	0	-10000	0	0
nuclear import	-0.017	0.01	-10000	0	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.005	0.069	0.39	7	-10000	0	7
VDR	0.02	0.003	-10000	0	-10000	0	0
FAM120B	0.019	0.005	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.016	0.028	0.22	2	-10000	0	2
RXRs/LXRs/DNA/Oxysterols	0.015	0.033	0.27	2	-10000	0	2
MED1	0.02	0.003	-10000	0	-10000	0	0
mol:9cRA	0.002	0.006	-10000	0	-10000	0	0
RARs/THRs/DNA/Src-1	-0.01	0.062	-10000	0	-0.18	33	33
RXRs/NUR77	0.046	0.039	-10000	0	-0.16	6	6
RXRs/PPAR	-0.006	0.056	-10000	0	-0.27	2	2
NCOR2	0.021	0.002	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.015	0.002	-10000	0	-10000	0	0
RARs/VDR/DNA/Vit D3	0.042	0.022	-10000	0	-0.15	2	2
RARA	0.02	0.002	-10000	0	-10000	0	0
NCOA1	0.02	0.004	-10000	0	-10000	0	0
VDR/VDR/DNA	0.02	0.003	-10000	0	-10000	0	0
RARs/RARs/DNA/9cRA	0.033	0.019	-10000	0	-0.14	2	2
RARG	0.02	0.003	-10000	0	-10000	0	0
RPS6KB1	-0.009	0.046	0.54	2	-10000	0	2
RARs/THRs/DNA/SMRT	-0.01	0.062	-10000	0	-0.18	34	34
THRA	0.02	0.003	-10000	0	-10000	0	0
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.015	0.002	-10000	0	-10000	0	0
RXRs/PPAR/9cRA/PGJ2/DNA	0.041	0.03	0.22	2	-0.15	1	3
NR1H4	-0.005	0.03	0.29	2	-10000	0	2
RXRs/LXRs/DNA	0.057	0.037	-10000	0	-10000	0	0
NR1H2	0.022	0.006	-10000	0	-10000	0	0
NR1H3	0.022	0.007	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.046	0.026	-10000	0	-0.15	1	1
NR4A1	0.014	0.044	-10000	0	-0.29	6	6
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	0.009	0.018	0.16	1	-10000	0	1
RXRG	0.019	0.025	0.3	1	-0.29	1	2
RXR alpha/CCPG	0.03	0.009	-10000	0	-10000	0	0
RXRA	0.022	0.005	-10000	0	-10000	0	0
RXRB	0.022	0.007	-10000	0	-10000	0	0
THRB	0.007	0.062	-10000	0	-0.29	12	12
PPARG	0	0.075	-10000	0	-0.29	18	18
PPARD	0.02	0.003	-10000	0	-10000	0	0
TNF	0.016	0.053	0.45	2	-10000	0	2
mol:Oxysterols	0.002	0.005	-10000	0	-10000	0	0
cholesterol transport	0.021	0.038	0.27	2	-10000	0	2
PPARA	0.02	0.004	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.017	0.026	-10000	0	-0.29	2	2
RXRs/NUR77/BCL2	0.004	0.038	-10000	0	-0.18	10	10
SREBF1	0.012	0.033	-10000	0	-10000	0	0
RXRs/RXRs/DNA/9cRA	0.041	0.03	0.22	2	-0.15	1	3
ABCA1	0.012	0.036	-10000	0	-10000	0	0
RARs/THRs	0.043	0.05	-10000	0	-0.16	14	14
RXRs/FXR	0.049	0.031	0.3	1	-0.16	1	2
BCL2	0.014	0.04	-10000	0	-0.29	5	5

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.021	0.001	-10000	0	-10000	0	0
HDAC3	0.02	0.004	-10000	0	-10000	0	0
VDR	0.02	0.003	-10000	0	-10000	0	0
Cbp/p300/PCAF	0.037	0.014	-10000	0	-10000	0	0
EP300	0.02	0.003	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.006	0.037	-10000	0	-0.43	1	1
KAT2B	0.019	0.005	-10000	0	-10000	0	0
MAPK14	0.02	0.003	-10000	0	-10000	0	0
AKT1	-0.019	0.061	0.19	3	-0.23	3	6
RAR alpha/9cRA/Cyclin H	0.025	0.056	-10000	0	-0.23	7	7
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	-0.001	0.056	0.16	1	-0.24	3	4
CDC2	0	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.018	0.037	-10000	0	-0.29	1	1
NCOR2	0.021	0.002	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.015	0.002	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA	-0.006	0.081	0.29	1	-0.36	6	7
NCOA2	0.015	0.036	-10000	0	-0.29	4	4
NCOA3	0.019	0.005	-10000	0	-10000	0	0
NCOA1	0.02	0.004	-10000	0	-10000	0	0
VDR/VDR/DNA	0.02	0.003	-10000	0	-10000	0	0
RARG	0.021	0.003	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.027	0.006	-10000	0	-10000	0	0
MAPK3	0.021	0.002	-10000	0	-10000	0	0
MAPK1	0.02	0.002	-10000	0	-10000	0	0
MAPK8	0.018	0.026	-10000	0	-0.29	2	2
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.02	0.071	-10000	0	-0.34	7	7
RARA	0.008	0.039	-10000	0	-0.19	7	7
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.003	0.056	0.16	1	-0.24	4	5
PRKCA	0.014	0.044	-10000	0	-0.29	6	6
RXRs/RARs/NRIP1/9cRA/HDAC1	0.005	0.094	0.39	2	-0.36	6	8
RXRG	0.012	0.051	-10000	0	-0.23	7	7
RXRA	0.002	0.033	-10000	0	-0.17	6	6
RXRB	0.014	0.049	0.24	1	-0.23	6	7
VDR/Vit D3/DNA	0.015	0.002	-10000	0	-10000	0	0
RBP1	0.009	0.044	-10000	0	-0.29	6	6
CRBP1/9-cic-RA	0.007	0.03	-10000	0	-0.2	6	6
RARB	0.017	0.026	-10000	0	-0.29	2	2
PRKCG	0.04	0.073	0.3	22	-10000	0	22
MNAT1	0.02	0.003	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.013	0.088	0.25	2	-0.4	7	9
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.003	0.075	-10000	0	-0.32	7	7
proteasomal ubiquitin-dependent protein catabolic process	0	0.079	0.35	2	-0.27	7	9
RXRs/RARs/NRIP1/9cRA/HDAC3	0.003	0.095	0.39	2	-0.36	6	8
positive regulation of DNA binding	0.018	0.051	-10000	0	-0.22	7	7
NRIP1	0.002	0.099	0.43	1	-0.54	1	2
RXRs/RARs	0.004	0.1	0.49	1	-0.36	6	7
RXRs/RXRs/DNA/9cRA	0.005	0.068	-10000	0	-0.34	7	7
PRKACA	0.02	0.004	-10000	0	-10000	0	0
CDK7	0.02	0.004	-10000	0	-10000	0	0
TFIIH	0.039	0.011	-10000	0	-10000	0	0
RAR alpha/9cRA	0.036	0.046	-10000	0	-0.19	1	1
CCNH	0.02	0.004	-10000	0	-10000	0	0
CREBBP	0.02	0.004	-10000	0	-10000	0	0
RAR gamma2/9cRA	0.035	0.015	-10000	0	-10000	0	0

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.029	0.035	0.28	1	-10000	0	1
DAPP1	0.011	0.072	0.2	5	-0.23	3	8
Src family/SYK family/BLNK-LAT/BTK-ITK	0.019	0.085	0.25	1	-0.3	5	6
mol:DAG	0.008	0.063	0.21	12	-10000	0	12
HRAS	0.02	0.006	-10000	0	-10000	0	0
RAP1A	0.021	0.004	-10000	0	-10000	0	0
ARF5/GDP	0.012	0.057	0.22	1	-0.22	6	7
PLCG2	0.02	0.004	-10000	0	-10000	0	0
PLCG1	0.019	0.005	-10000	0	-10000	0	0
ARF5	0.02	0.004	-10000	0	-10000	0	0
mol:GTP	-0.023	0.033	0.15	8	-10000	0	8
ARF1/GTP	-0.018	0.027	0.22	1	-10000	0	1
RHOA	0.019	0.006	-10000	0	-10000	0	0
YES1	0.02	0.005	-10000	0	-10000	0	0
RAP1A/GTP	-0.023	0.029	0.15	7	-10000	0	7
ADAP1	-0.025	0.033	0.2	2	-10000	0	2
ARAP3	-0.023	0.032	0.15	8	-10000	0	8
INPPL1	0.02	0.004	-10000	0	-10000	0	0
PREX1	0.019	0.005	-10000	0	-10000	0	0
ARHGEF6	0.017	0.031	-10000	0	-0.29	3	3
ARHGEF7	0.02	0.004	-10000	0	-10000	0	0
ARF1	0.019	0.005	-10000	0	-10000	0	0
NRAS	0.021	0.004	-10000	0	-10000	0	0
FYN	0.015	0.04	-10000	0	-0.29	5	5
ARF6	0.02	0.003	-10000	0	-10000	0	0
FGR	0.02	0.002	-10000	0	-10000	0	0
mol:Ca2+	0.004	0.046	0.14	19	-10000	0	19
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.018	0.026	-10000	0	-0.29	2	2
ZAP70	0.02	0.002	-10000	0	-10000	0	0
mol:IP3	0.003	0.057	0.17	19	-10000	0	19
LYN	0.02	0.004	-10000	0	-10000	0	0
ARF1/GDP	0.011	0.054	-10000	0	-0.22	4	4
RhoA/GDP	-0.016	0.043	0.2	1	-10000	0	1
PDK1/Src/Hsp90	0.036	0.015	-10000	0	-10000	0	0
BLNK	0.021	0.016	0.29	1	-10000	0	1
actin cytoskeleton reorganization	-0.005	0.061	0.39	1	-0.25	1	2
SRC	0.019	0.006	-10000	0	-10000	0	0
PLEKHA2	-0.018	0.008	-10000	0	-10000	0	0
RAC1	0.02	0.003	-10000	0	-10000	0	0
PTEN	0.02	0.011	-10000	0	-10000	0	0
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
ARF6/GTP	-0.025	0.043	0.28	1	-10000	0	1
RhoA/GTP	-0.025	0.033	0.29	1	-10000	0	1
Src family/SYK family/BLNK-LAT	0.008	0.06	-10000	0	-0.32	1	1
BLK	0.064	0.11	0.29	52	-10000	0	52
PDPK1	0.02	0.004	-10000	0	-10000	0	0
CYTH1	-0.027	0.025	0.14	1	-10000	0	1
HCK	0.019	0.006	-10000	0	-10000	0	0
CYTH3	-0.026	0.033	0.2	2	-10000	0	2
CYTH2	-0.025	0.033	0.2	2	-10000	0	2
KRAS	0.02	0.006	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	-0.007	0.031	-10000	0	-10000	0	0
SGK1	-0.004	0.058	-10000	0	-0.33	6	6
INPP5D	0.018	0.007	-10000	0	-10000	0	0
mol:GDP	0.001	0.057	0.22	1	-0.21	9	10
SOS1	0.02	0.003	-10000	0	-10000	0	0
SYK	0.02	0.003	-10000	0	-10000	0	0
ARF6/GDP	-0.018	0.045	0.24	3	-10000	0	3
mol:PI-3-4-5-P3	-0.023	0.032	0.14	9	-10000	0	9
ARAP3/RAP1A/GTP	-0.023	0.029	0.15	7	-10000	0	7
VAV1	0.02	0.004	-10000	0	-10000	0	0
mol:PI-3-4-P2	-0.016	0.006	-10000	0	-10000	0	0
RAS family/GTP/PI3K Class I	-0.015	0.052	0.18	19	-10000	0	19
PLEKHA1	-0.019	0.008	-10000	0	-10000	0	0
Rac1/GDP	0.012	0.058	0.22	1	-0.21	9	10
LAT	0.02	0.002	-10000	0	-10000	0	0
Rac1/GTP	0	0.047	-10000	0	-0.24	6	6
ITK	-0.026	0.032	0.27	1	-10000	0	1
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.005	0.07	0.22	10	-0.21	1	11
LCK	0.021	0.001	-10000	0	-10000	0	0
BTK	-0.027	0.032	0.2	2	-10000	0	2

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	-0.021	0.028	-10000	0	-0.48	1	1
VEGFR1 homodimer/NRP1	-0.014	0.027	-10000	0	-0.48	1	1
mol:DAG	-0.021	0.031	0.18	2	-0.45	1	3
VEGFR1 homodimer/NRP1/VEGFR 121	-0.018	0.026	-10000	0	-0.45	1	1
CaM/Ca2+	-0.024	0.03	0.17	2	-0.43	1	3
HIF1A	0.021	0.018	-10000	0	-0.29	1	1
GAB1	0.02	0.003	-10000	0	-10000	0	0
AKT1	0.025	0.081	0.35	3	-0.27	1	4
PLCG1	-0.021	0.031	0.18	2	-0.45	1	3
NOS3	0.007	0.078	0.31	4	-0.29	5	9
CBL	0.017	0.008	-10000	0	-10000	0	0
mol:NO	0.017	0.099	0.36	9	-0.34	3	12
FLT1	-0.018	0.032	-10000	0	-0.55	1	1
PGF	0.02	0.003	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP2/VEGFR121	0.021	0.039	-10000	0	-0.45	1	1
CALM1	0.02	0.005	-10000	0	-10000	0	0
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
eNOS/Hsp90	0.009	0.09	0.28	5	-0.31	5	10
endothelial cell proliferation	0.006	0.076	0.37	6	-0.42	1	7
mol:Ca2+	-0.021	0.031	0.18	2	-0.44	1	3
MAPK3	-0.026	0.051	0.26	5	-0.41	1	6
MAPK1	-0.026	0.051	0.26	5	-0.41	1	6
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
PLGF homodimer	0.02	0.003	-10000	0	-10000	0	0
PRKACA	0.02	0.004	-10000	0	-10000	0	0
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	-0.008	0.088	-10000	0	-0.29	26	26
VEGFA homodimer	0.02	0.004	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	-0.02	0.028	-10000	0	-0.48	1	1
platelet activating factor biosynthetic process	-0.03	0.049	0.32	3	-0.4	1	4
PI3K	0.024	0.027	-10000	0	-0.26	1	1
PRKCA	-0.027	0.035	0.16	2	-0.42	1	3
PRKCB	-0.025	0.031	0.16	2	-0.42	1	3
VEGFR1 homodimer/PLGF homodimer	-0.021	0.028	-10000	0	-0.48	1	1
VEGFA	0.02	0.004	-10000	0	-10000	0	0
VEGFB	0.02	0.003	-10000	0	-10000	0	0
mol:IP3	-0.021	0.031	0.18	2	-0.45	1	3
RASA1	-0.02	0.038	0.18	6	-0.45	1	7
NRP2	0.014	0.041	-10000	0	-0.29	5	5
VEGFR1 homodimer	-0.018	0.032	-10000	0	-0.55	1	1
VEGFB homodimer	0.02	0.003	-10000	0	-10000	0	0
NCK1	0.015	0.009	-10000	0	-10000	0	0
eNOS/Caveolin-1	0.011	0.1	0.39	7	-0.34	5	12
PTPN11	0.021	0.001	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.023	0.026	-10000	0	-0.25	1	1
mol:L-citrulline	0.017	0.099	0.36	9	-0.34	3	12
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.031	0.032	-10000	0	-0.42	1	1
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.02	0.022	-10000	0	-0.27	1	1
CD2AP	0.02	0.004	-10000	0	-10000	0	0
PI3K/GAB1	0.029	0.032	-10000	0	-0.25	1	1
PDPK1	0.031	0.09	0.32	4	-0.25	1	5
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.027	0.03	-10000	0	-0.45	1	1
mol:NADP	0.017	0.099	0.36	9	-0.34	3	12
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.03	0.032	-10000	0	-0.41	1	1
VEGFR1 homodimer/NRP2	-0.022	0.035	-10000	0	-0.48	1	1

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.012	0.015	-10000	0	-0.085	5	5
TRAF2/ASK1	0.027	0.006	-10000	0	-10000	0	0
ATM	0.018	0.007	-10000	0	-10000	0	0
MAP2K3	-0.033	0.11	-10000	0	-0.33	19	19
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	-0.028	0.086	0.19	1	-0.33	10	11
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	-0.008	0.09	-10000	0	-0.29	27	27
TXN	0.004	0.007	0.12	1	-10000	0	1
CALM1	0.02	0.005	-10000	0	-10000	0	0
GADD45A	0.02	0.002	-10000	0	-10000	0	0
GADD45B	0.019	0.005	-10000	0	-10000	0	0
MAP3K1	0.02	0.005	-10000	0	-10000	0	0
MAP3K6	0.02	0.003	-10000	0	-10000	0	0
MAP3K7	0.02	0.004	-10000	0	-10000	0	0
MAP3K4	0.019	0.005	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.029	0.007	-10000	0	-10000	0	0
TAK1/TAB family	0.003	0.014	-10000	0	-0.13	1	1
RAC1/OSM/MEKK3	0.038	0.009	-10000	0	-10000	0	0
TRAF2	0.02	0.003	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.012	0.094	-10000	0	-0.27	17	17
TRAF6	0.003	0.001	-10000	0	-10000	0	0
RAC1	0.02	0.003	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	0.041	0.072	0.29	22	-10000	0	22
CCM2	0.02	0.002	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	0.037	0.042	0.19	19	-10000	0	19
MAPK11	0.02	0.004	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.046	0.041	0.2	18	-10000	0	18
OSM/MEKK3	0.03	0.006	-10000	0	-10000	0	0
TAOK1	0.006	0.002	-10000	0	-10000	0	0
TAOK2	0.006	0.002	-10000	0	-10000	0	0
TAOK3	0.006	0.002	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.02	0.003	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.02	0.004	-10000	0	-10000	0	0
MAP3K10	0.02	0.005	-10000	0	-10000	0	0
MAP3K3	0.02	0.004	-10000	0	-10000	0	0
TRX/ASK1	0.017	0.006	-10000	0	-10000	0	0
GADD45/MTK1/MTK1	0.026	0.058	-10000	0	-0.15	27	27

×

Canonical NF-kappaB 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
FBXW11	0.02	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.003	0.077	0.3	1	-0.26	8	9
ERC1	0.02	0.005	-10000	0	-10000	0	0
RIP2/NOD2	0.03	0.021	0.22	3	-10000	0	3
NFKBIA	-0.02	0.019	0.19	2	-10000	0	2
BIRC2	0.016	0.008	-10000	0	-10000	0	0
IKBKB	0.02	0.005	-10000	0	-10000	0	0
RIPK2	0.02	0.004	-10000	0	-10000	0	0
IKBKG	-0.008	0.073	-10000	0	-0.45	6	6
IKK complex/A20	0.023	0.095	0.32	1	-0.38	10	11
NEMO/A20/RIP2	0.02	0.004	-10000	0	-10000	0	0
XPO1	0.02	0.003	-10000	0	-10000	0	0
NEMO/ATM	0.015	0.087	-10000	0	-0.38	11	11
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.02	0.002	-10000	0	-10000	0	0
Exportin 1/RanGTP	0.027	0.005	-10000	0	-10000	0	0
IKK complex/ELKS	0.015	0.089	-10000	0	-0.38	10	10
BCL10/MALT1/TRAF6	0.038	0.012	-10000	0	-10000	0	0
NOD2	0.023	0.028	0.29	3	-10000	0	3
NFKB1	0.021	0.003	-10000	0	-10000	0	0
RELA	0.021	0.003	-10000	0	-10000	0	0
MALT1	0.02	0.005	-10000	0	-10000	0	0
cIAP1/UbcH5C	0.024	0.013	-10000	0	-10000	0	0
ATM	0.018	0.007	-10000	0	-10000	0	0
TNF/TNFR1A	0.03	0.024	0.22	4	-10000	0	4
TRAF6	0.02	0.004	-10000	0	-10000	0	0
PRKCA	0.014	0.044	-10000	0	-0.29	6	6
CHUK	0.02	0.003	-10000	0	-10000	0	0
UBE2D3	0.02	0.003	-10000	0	-10000	0	0
TNF	0.023	0.032	0.29	4	-10000	0	4
NF kappa B1 p50/RelA	0.041	0.012	-10000	0	-10000	0	0
BCL10	0.021	0.002	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.02	0.019	0.19	2	-10000	0	2
beta TrCP1/SCF ubiquitin ligase complex	0.02	0.005	-10000	0	-10000	0	0
TNFRSF1A	0.019	0.005	-10000	0	-10000	0	0
IKK complex	0.017	0.095	-10000	0	-0.4	10	10
CYLD	0.02	0.004	-10000	0	-10000	0	0
IKK complex/PKC alpha	0.019	0.098	-10000	0	-0.39	11	11

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.026	0.012	-10000	0	-10000	0	0
ATM	0.018	0.007	-10000	0	-10000	0	0
UBE2D3	0.02	0.003	-10000	0	-10000	0	0
PRKDC	0.02	0.004	-10000	0	-10000	0	0
ATR	0.015	0.009	-10000	0	-10000	0	0
UBE2L3	0.02	0.003	-10000	0	-10000	0	0
FANCD2	0.006	0.005	-10000	0	-10000	0	0
protein ubiquitination	0.042	0.034	0.19	4	-0.16	1	5
XRCC5	0.019	0.006	-10000	0	-10000	0	0
XRCC6	0.02	0.003	-10000	0	-10000	0	0
M/R/N Complex	0.034	0.017	-10000	0	-10000	0	0
MRE11A	0.018	0.007	-10000	0	-10000	0	0
DNA-PK	0.036	0.015	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.006	0.068	-10000	0	-0.36	3	3
FANCF	0.019	0.019	-10000	0	-0.29	1	1
BRCA1	0.02	0.002	-10000	0	-10000	0	0
CCNE1	0.024	0.032	0.29	4	-10000	0	4
CDK2/Cyclin E1	0.032	0.023	0.22	4	-10000	0	4
FANCG	0.02	0.003	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.027	0.016	-10000	0	-0.2	1	1
FANCE	0.02	0.003	-10000	0	-10000	0	0
FANCC	0.02	0.002	-10000	0	-10000	0	0
NBN	0.02	0.004	-10000	0	-10000	0	0
FANCA	0.039	0.071	0.29	21	-10000	0	21
DNA repair	-0.004	0.073	0.23	10	-0.3	3	13
BRCA1/BARD1/ubiquitin	0.027	0.016	-10000	0	-0.2	1	1
BARD1/DNA-PK	0.044	0.023	-10000	0	-0.16	1	1
FANCL	0.02	0.003	-10000	0	-10000	0	0
mRNA polyadenylation	-0.025	0.012	-10000	0	-10000	0	0
BRCA1/BARD1/CTIP/M/R/N Complex	-0.015	0.068	-10000	0	-0.21	29	29
BRCA1/BACH1/BARD1/TopBP1	0.029	0.019	-10000	0	-10000	0	0
BRCA1/BARD1/P53	0.033	0.026	-10000	0	-10000	0	0
BARD1/CSTF1/BRCA1	0.035	0.016	-10000	0	-10000	0	0
BRCA1/BACH1	0.02	0.002	-10000	0	-10000	0	0
BARD1	0.018	0.019	-10000	0	-0.29	1	1
PCNA	0.019	0.005	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	0.036	0.018	-10000	0	-0.17	1	1
BRCA1/BARD1/UbcH7	0.036	0.019	-10000	0	-0.17	1	1
BRCA1/BARD1/RAD51/PCNA	0.043	0.028	0.21	2	-0.16	1	3
BARD1/DNA-PK/P53	0.047	0.029	-10000	0	-0.16	1	1
BRCA1/BARD1/Ubiquitin	0.027	0.016	-10000	0	-0.2	1	1
BRCA1/BARD1/CTIP	0.023	0.017	-10000	0	-0.16	1	1
FA complex	0.029	0.05	0.17	5	-0.2	4	9
BARD1/EWS	0.027	0.016	-10000	0	-0.2	1	1
RBBP8	-0.015	0.007	-10000	0	-10000	0	0
TP53	0.019	0.006	-10000	0	-10000	0	0
TOPBP1	0.016	0.009	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.031	0.025	-10000	0	-10000	0	0
BRCA1/BARD1	0.048	0.037	0.21	4	-0.16	1	5
CSTF1	0.019	0.005	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.013	0.013	-10000	0	-0.2	1	1
CDK2	0.02	0.002	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.024	0.036	0.29	5	-10000	0	5
RAD50	0.02	0.005	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.027	0.016	-10000	0	-0.2	1	1
EWSR1	0.02	0.003	-10000	0	-10000	0	0

×

JNK signaling in the CD4+ TCR 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
LAT/GRAP2/SLP76/HPK1	0.047	0.018	-10000	0	-10000	0	0
MAP4K1	0.019	0.005	-10000	0	-10000	0	0
MAP3K8	0.02	0.004	-10000	0	-10000	0	0
PRKCB	0.018	0.026	-10000	0	-0.29	2	2
DBNL	0.02	0.002	-10000	0	-10000	0	0
CRKL	0.02	0.003	-10000	0	-10000	0	0
MAP3K1	-0.007	0.03	-10000	0	-0.19	1	1
JUN	-0.01	0.12	-10000	0	-0.53	14	14
MAP3K7	-0.008	0.035	-10000	0	-0.21	3	3
GRAP2	0.02	0.003	-10000	0	-10000	0	0
CRK	0.019	0.006	-10000	0	-10000	0	0
MAP2K4	-0.009	0.045	0.16	1	-0.24	2	3
LAT	0.02	0.002	-10000	0	-10000	0	0
LCP2	0.02	0.004	-10000	0	-10000	0	0
MAPK8	-0.008	0.12	-10000	0	-0.55	14	14
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.004	0.041	-10000	0	-0.2	5	5
LAT/GRAP2/SLP76/HPK1/HIP-55	0.053	0.023	-10000	0	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	-0.011	0.008	-10000	0	-10000	0	0
CRKL	0.02	0.003	-10000	0	-10000	0	0
Rac1/GDP	0.015	0.002	-10000	0	-10000	0	0
DOCK1	0.02	0.003	-10000	0	-10000	0	0
ITGA4	0.02	0.004	-10000	0	-10000	0	0
alpha4/beta7 Integrin/MAdCAM1	0.045	0.021	0.21	1	-10000	0	1
EPO	-0.004	0.076	-10000	0	-0.29	19	19
alpha4/beta7 Integrin	0.029	0.007	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.019	0.006	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.029	0.007	-10000	0	-10000	0	0
EPO/EPOR (dimer)	0.014	0.056	-10000	0	-0.2	18	18
lamellipodium assembly	0.037	0.057	-10000	0	-10000	0	0
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
PI3K	0.019	0.015	-10000	0	-10000	0	0
ARF6	0.02	0.003	-10000	0	-10000	0	0
JAK2	-0.001	0.046	-10000	0	-0.18	18	18
PXN	0.021	0.001	-10000	0	-10000	0	0
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
MADCAM1	0.014	0.022	0.29	1	-10000	0	1
cell adhesion	0.044	0.021	0.2	1	-10000	0	1
CRKL/CBL	0.025	0.012	-10000	0	-10000	0	0
ITGB1	0.02	0.003	-10000	0	-10000	0	0
SRC	-0.023	0.034	0.17	5	-0.16	7	12
ITGB7	0.02	0.003	-10000	0	-10000	0	0
RAC1	0.02	0.003	-10000	0	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.034	0.036	-10000	0	-0.17	8	8
p130Cas/Crk/Dock1	-0.029	0.037	0.17	6	-10000	0	6
VCAM1	0.012	0.051	-10000	0	-0.29	8	8
RHOA	0.019	0.006	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.049	0.015	-10000	0	-10000	0	0
BCAR1	-0.026	0.033	0.16	5	-10000	0	5
EPOR	0.02	0.004	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.017	0.008	-10000	0	-10000	0	0
GIT1	0.02	0.003	-10000	0	-10000	0	0
Rac1/GTP	0.038	0.058	-10000	0	-10000	0	0

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.013	0.01	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0.018	0.015	-10000	0	-10000	0	0
MAP2K4	0.001	0.023	-10000	0	-0.24	1	1
IKBKB	0.02	0.005	-10000	0	-10000	0	0
TNFRSF10B	0.019	0.006	-10000	0	-10000	0	0
TNFRSF10A	0.019	0.006	-10000	0	-10000	0	0
SMPD1	0.003	0.003	-10000	0	-10000	0	0
IKBKG	0.02	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.019	0.006	-10000	0	-10000	0	0
TRAIL/TRAILR2	0.018	0.015	-10000	0	-10000	0	0
TRAIL/TRAILR3	0.018	0.015	-10000	0	-10000	0	0
TRAIL/TRAILR1	0.018	0.015	-10000	0	-10000	0	0
TRAIL/TRAILR4	0.018	0.015	-10000	0	-10000	0	0
TRAIL/TRAILR1/DAP3/GTP	0.023	0.02	-10000	0	-10000	0	0
IKK complex	0.001	0.035	-10000	0	-10000	0	0
RIPK1	0.02	0.005	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.014	0.004	-10000	0	-10000	0	0
MAPK3	-0.011	0.018	0.26	1	-10000	0	1
MAP3K1	0.005	0.025	-10000	0	-0.25	1	1
TRAILR4 (trimer)	0.019	0.006	-10000	0	-10000	0	0
TRADD	0.02	0.004	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.019	0.006	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.003	0.026	-10000	0	-0.18	1	1
CFLAR	0.019	0.005	-10000	0	-10000	0	0
MAPK1	-0.011	0.019	0.26	1	-10000	0	1
TRAIL/TRAILR1/FADD/TRADD/RIP	0.033	0.033	-10000	0	-10000	0	0
mol:ceramide	0.003	0.003	-10000	0	-10000	0	0
FADD	0.019	0.005	-10000	0	-10000	0	0
MAPK8	0.01	0.049	-10000	0	-0.25	2	2
TRAF2	0.02	0.003	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.019	0.006	-10000	0	-10000	0	0
CHUK	0.02	0.003	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	0.024	0.021	-10000	0	-10000	0	0
DAP3	0.019	0.005	-10000	0	-10000	0	0
CASP10	0.035	0.072	0.15	86	-10000	0	86
JNK cascade	0.018	0.015	-10000	0	-10000	0	0
TRAIL (trimer)	0.013	0.01	-10000	0	-10000	0	0
TNFRSF10C	0.019	0.006	-10000	0	-10000	0	0
TRAIL/TRAILR1/DAP3/GTP/FADD	0.027	0.025	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD	0.024	0.021	-10000	0	-10000	0	0
cell death	0.003	0.003	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.003	0.026	0.14	1	-0.18	1	2
TRAILR2 (trimer)	0.019	0.006	-10000	0	-10000	0	0
CASP8	-0.019	0.12	-10000	0	-0.57	13	13
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.033	0.033	-10000	0	-10000	0	0

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.032	0.059	-10000	0	-10000	0	0
UGCG	0.016	0.029	-10000	0	-0.4	1	1
AKT1/mTOR/p70S6K/Hsp90/TERT	0.04	0.078	0.26	1	-0.39	2	3
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.018	0.029	-10000	0	-0.4	1	1
mol:DAG	-0.002	0.12	-10000	0	-0.78	6	6
CaM/Ca2+/Calcineurin A alpha-beta B1	0.033	0.08	-10000	0	-0.34	5	5
FRAP1	0.031	0.086	-10000	0	-0.38	5	5
FOXO3	0.027	0.074	-10000	0	-0.36	3	3
AKT1	0.031	0.078	-10000	0	-0.38	3	3
GAB2	0.017	0.02	-10000	0	-0.29	1	1
SMPD1	-0.008	0.12	-10000	0	-0.55	14	14
SGMS1	0.006	0.086	-10000	0	-0.57	6	6
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	-0.009	0.007	-10000	0	-10000	0	0
CALM1	0.02	0.005	-10000	0	-10000	0	0
cell proliferation	0.03	0.07	-10000	0	-0.39	3	3
EIF3A	0.02	0.003	-10000	0	-10000	0	0
PI3K	0.019	0.017	-10000	0	-10000	0	0
RPS6KB1	0.029	0.056	-10000	0	-0.7	1	1
mol:sphingomyelin	-0.002	0.12	-10000	0	-0.78	6	6
natural killer cell activation	0	0.002	-10000	0	-10000	0	0
JAK3	0.02	0.008	-10000	0	-10000	0	0
PIK3R1	0.019	0.009	-10000	0	-10000	0	0
JAK1	0.02	0.008	-10000	0	-10000	0	0
NFKB1	0.02	0.003	-10000	0	-10000	0	0
MYC	0.034	0.12	-10000	0	-0.82	4	4
MYB	0.045	0.086	0.37	5	-10000	0	5
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.029	0.055	-10000	0	-0.28	1	1
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.047	0.053	-10000	0	-0.66	1	1
mol:PI-3-4-5-P3	0.028	0.055	-10000	0	-0.27	1	1
Rac1/GDP	-0.01	0.011	-10000	0	-10000	0	0
T cell proliferation	0.026	0.055	-10000	0	-0.26	1	1
SHC1	0.018	0.009	-10000	0	-10000	0	0
RAC1	0.02	0.003	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.01	0.025	0.079	34	-10000	0	34
PRKCZ	0.027	0.055	-10000	0	-0.27	1	1
NF kappa B1 p50/RelA	0.046	0.084	-10000	0	-0.35	4	4
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.003	0.025	-10000	0	-10000	0	0
HSP90AA1	0.02	0.004	-10000	0	-10000	0	0
RELA	0.02	0.003	-10000	0	-10000	0	0
IL2RA	0.026	0.043	0.3	7	-10000	0	7
IL2RB	0.02	0.007	-10000	0	-10000	0	0
TERT	-0.014	0.007	-10000	0	-10000	0	0
E2F1	0.045	0.073	0.34	5	-10000	0	5
SOS1	0.019	0.008	-10000	0	-10000	0	0
RPS6	0.02	0.004	-10000	0	-10000	0	0
mol:cAMP	-0.005	0.014	-10000	0	-0.043	34	34
PTPN11	0.02	0.008	-10000	0	-10000	0	0
IL2RG	0.023	0.029	0.3	3	-10000	0	3
actin cytoskeleton organization	0.026	0.055	-10000	0	-0.26	1	1
GRB2	0.019	0.009	-10000	0	-10000	0	0
IL2	0.018	0.009	-10000	0	-10000	0	0
PIK3CA	0.013	0.011	-10000	0	-10000	0	0
Rac1/GTP	0.024	0.021	-10000	0	-10000	0	0
LCK	0.02	0.008	-10000	0	-10000	0	0
BCL2	0.02	0.12	0.34	1	-0.74	5	6

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.044	0.1	0.54	1	-10000	0	1
CRP	0.037	0.11	0.49	2	-10000	0	2
cell cycle arrest	0.03	0.093	-10000	0	-10000	0	0
TIMP1	0.033	0.1	-10000	0	-0.52	3	3
IL6ST	0.01	0.06	-10000	0	-0.29	11	11
Rac1/GDP	0.024	0.063	-10000	0	-0.3	2	2
AP1	0.042	0.11	-10000	0	-0.39	3	3
GAB2	0.02	0.02	-10000	0	-0.29	1	1
TNFSF11	0.031	0.1	0.43	1	-10000	0	1
HSP90B1	0.03	0.039	-10000	0	-10000	0	0
GAB1	0.021	0.005	-10000	0	-10000	0	0
MAPK14	-0.005	0.052	-10000	0	-0.32	1	1
AKT1	0.023	0.047	0.27	1	-10000	0	1
FOXO1	0.018	0.048	0.24	1	-10000	0	1
MAP2K6	0.001	0.05	-10000	0	-0.33	1	1
mol:GTP	0	0.001	-10000	0	-10000	0	0
MAP2K4	0.022	0.065	0.26	2	-0.35	1	3
MITF	-0.013	0.066	0.19	2	-0.29	3	5
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.02	0.004	-10000	0	-10000	0	0
A2M	-0.11	0.36	-10000	0	-1.1	32	32
CEBPB	0.021	0.007	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.032	0.083	-10000	0	-0.36	3	3
STAT3	0.031	0.093	-10000	0	-10000	0	0
STAT1	0.007	0.1	-10000	0	-0.68	6	6
CEBPD	0.031	0.092	-10000	0	-10000	0	0
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
PI3K	0.019	0.015	-10000	0	-10000	0	0
JUN	0.019	0.018	-10000	0	-0.29	1	1
PIAS3/MITF	-0.009	0.076	-10000	0	-0.28	3	3
MAPK11	-0.004	0.051	-10000	0	-0.32	1	1
STAT3 (dimer)/FOXO1	0.024	0.11	0.4	2	-0.57	1	3
GRB2/SOS1/GAB family	0.049	0.074	0.23	1	-0.3	2	3
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	0.011	0.051	-10000	0	-0.27	2	2
GRB2	0.021	0.006	-10000	0	-10000	0	0
JAK2	0.019	0.005	-10000	0	-10000	0	0
LBP	0.05	0.097	0.46	3	-10000	0	3
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
JAK1	0.022	0.006	-10000	0	-10000	0	0
MYC	0.031	0.14	-10000	0	-0.85	4	4
FGG	0.023	0.087	-10000	0	-10000	0	0
macrophage differentiation	0.03	0.093	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0.047	0.062	0.23	5	-0.23	2	7
JUNB	0.027	0.09	-10000	0	-10000	0	0
FOS	-0.003	0.082	-10000	0	-0.29	22	22
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	0.016	0.056	0.23	1	-0.31	2	3
STAT1/PIAS1	0.035	0.068	0.26	2	-10000	0	2
GRB2/SOS1/GAB family/SHP2/PI3K	0.03	0.045	-10000	0	-0.26	1	1
STAT3 (dimer)	0.029	0.094	-10000	0	-10000	0	0
PRKCD	0.011	0.074	-10000	0	-0.42	1	1
IL6R	0.016	0.037	-10000	0	-0.29	4	4
SOCS3	-0.002	0.057	-10000	0	-10000	0	0
gp130 (dimer)/JAK1/JAK1/LMO4	0.038	0.045	-10000	0	-0.17	11	11
Rac1/GTP	0.025	0.064	-10000	0	-0.31	2	2
HCK	0.019	0.007	-10000	0	-10000	0	0
MAPKKK cascade	0.037	0.098	-10000	0	-0.4	5	5
bone resorption	0.031	0.099	0.43	1	-10000	0	1
IRF1	0.026	0.086	-10000	0	-10000	0	0
mol:GDP	0.005	0.054	0.2	2	-0.3	2	4
SOS1	0.022	0.007	-10000	0	-10000	0	0
VAV1	0.005	0.055	0.21	2	-0.3	2	4
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	0.01	0.06	-10000	0	-0.34	4	4
PTPN11	0.022	0.041	-10000	0	-0.63	1	1
IL6/IL6RA	0.033	0.043	0.23	7	-0.2	4	11
gp130 (dimer)/TYK2/TYK2/LMO4	0.034	0.044	-10000	0	-0.17	11	11
gp130 (dimer)/JAK2/JAK2/LMO4	0.033	0.044	-10000	0	-0.17	11	11
IL6	0.029	0.044	0.3	7	-10000	0	7
PIAS3	0.019	0.005	-10000	0	-10000	0	0
PTPRE	0.013	0.017	-10000	0	-10000	0	0
PIAS1	0.02	0.003	-10000	0	-10000	0	0
RAC1	0.02	0.004	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	0.005	0.054	-10000	0	-0.27	3	3
LMO4	0.023	0.007	-10000	0	-10000	0	0
STAT3 (dimer)/PIAS3	0.034	0.088	-10000	0	-10000	0	0
MCL1	0.034	0.073	0.33	1	-10000	0	1

×

IL2 signaling events mediated by STAT5

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
GAB2	0.018	0.019	-10000	0	-0.29	1	1
ELF1	0.024	0.022	0.16	7	-10000	0	7
CCNA2	0.022	0.023	0.29	2	-10000	0	2
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
JAK3	0.02	0.003	-10000	0	-10000	0	0
PIK3R1	0.02	0.004	-10000	0	-10000	0	0
JAK1	0.021	0.002	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.031	0.051	-10000	0	-10000	0	0
SHC1	0.019	0.006	-10000	0	-10000	0	0
SP1	0.012	0.055	-10000	0	-0.28	10	10
IL2RA	-0.008	0.044	0.27	7	-10000	0	7
IL2RB	0.021	0.002	-10000	0	-10000	0	0
SOS1	0.02	0.003	-10000	0	-10000	0	0
IL2RG	0.023	0.028	0.29	3	-10000	0	3
G1/S transition of mitotic cell cycle	-0.022	0.13	0.27	2	-0.56	12	14
PTPN11	0.021	0.001	-10000	0	-10000	0	0
CCND2	-0.032	0.093	-10000	0	-0.55	9	9
LCK	0.021	0.001	-10000	0	-10000	0	0
GRB2	0.02	0.005	-10000	0	-10000	0	0
IL2	0.018	0.005	-10000	0	-10000	0	0
CDK6	0.02	0.005	-10000	0	-10000	0	0
CCND3	0.027	0.054	0.28	1	-10000	0	1

×

Arf6 trafficking events

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
SLC2A4	-0.077	0.14	-10000	0	-0.29	90	90
CLTC	0.017	0.023	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.004	0.017	-10000	0	-0.16	1	1
Dynamin 2/GTP	-0.018	0.005	-10000	0	-10000	0	0
EXOC4	0.02	0.004	-10000	0	-10000	0	0
CD59	0.004	0.012	-10000	0	-10000	0	0
CPE	-0.022	0.034	-10000	0	-0.17	15	15
CTNNB1	0.019	0.006	-10000	0	-10000	0	0
membrane fusion	0.004	0.015	-10000	0	-10000	0	0
CTNND1	-0.016	0.035	0.17	10	-10000	0	10
DNM2	0.02	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.003	0.028	0.16	2	-10000	0	2
TSHR	-0.014	0.01	0.15	1	-10000	0	1
INS	-0.008	0.099	-10000	0	-0.43	15	15
BIN1	0.02	0.002	-10000	0	-10000	0	0
mol:Choline	0.004	0.015	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	-0.014	0.003	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.02	0.003	-10000	0	-10000	0	0
mol:Ca2+	-0.018	0.005	-10000	0	-10000	0	0
JUP	0.004	0.013	-10000	0	-10000	0	0
ASAP2/amphiphysin II	0.037	0.01	-10000	0	-10000	0	0
ARF6/GTP	0.015	0.003	-10000	0	-10000	0	0
CDH1	0.064	0.038	0.2	1	-10000	0	1
clathrin-independent pinocytosis	0.015	0.002	-10000	0	-10000	0	0
MAPK8IP3	0.02	0.004	-10000	0	-10000	0	0
positive regulation of endocytosis	0.015	0.002	-10000	0	-10000	0	0
EXOC2	0.02	0.005	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	-0.004	0.039	-10000	0	-0.33	1	1
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.02	0.002	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.041	0.022	-10000	0	-10000	0	0
positive regulation of phagocytosis	-0.014	0.004	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.026	0.007	-10000	0	-10000	0	0
ACAP1	0.006	0.018	-10000	0	-0.15	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.004	0.012	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.007	0.025	0.23	1	-10000	0	1
JIP4/KLC1	0.037	0.01	-10000	0	-10000	0	0
EXOC1	0.02	0.004	-10000	0	-10000	0	0
exocyst	-0.004	0.039	-10000	0	-0.34	1	1
RALA/GTP	0.015	0.002	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.027	0.006	-10000	0	-10000	0	0
receptor recycling	0.015	0.002	-10000	0	-10000	0	0
CTNNA1	-0.016	0.034	0.17	9	-10000	0	9
NME1	-0.014	0.003	-10000	0	-10000	0	0
clathrin coat assembly	0.019	0.03	0.25	1	-10000	0	1
IL2RA	0.005	0.015	-10000	0	-10000	0	0
VAMP3	-0.014	0.004	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.013	0.063	-10000	0	-10000	0	0
EXOC6	0.02	0.004	-10000	0	-10000	0	0
PLD1	0.003	0.003	-10000	0	-10000	0	0
PLD2	0.004	0.002	-10000	0	-10000	0	0
EXOC5	0.02	0.003	-10000	0	-10000	0	0
PIP5K1C	0.002	0.025	0.16	1	-10000	0	1
SDC1	0.067	0.036	0.2	1	-10000	0	1
ARF6/GDP	0.016	0.003	-10000	0	-10000	0	0
EXOC7	0.02	0.004	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.044	0.023	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.004	0.015	-10000	0	-10000	0	0
endocytosis	-0.036	0.01	-10000	0	-10000	0	0
SCAMP2	0.02	0.004	-10000	0	-10000	0	0
ADRB2	0.011	0.038	0.23	1	-10000	0	1
EXOC3	0.017	0.008	-10000	0	-10000	0	0
ASAP2	0.02	0.004	-10000	0	-10000	0	0
Dynamin 2/GDP	0.018	0.005	-10000	0	-10000	0	0
KLC1	0.02	0.004	-10000	0	-10000	0	0
AVPR2	-0.011	0.069	0.37	1	-0.27	1	2
RALA	0.02	0.002	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.031	0.023	-10000	0	-10000	0	0

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0.027	0.036	-10000	0	-0.15	11	11
MAPK9	0.003	0.001	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.01	0.002	-10000	0	-10000	0	0
GNB1/GNG2	0.026	0.007	-10000	0	-10000	0	0
GNB1	0.02	0.004	-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	0.003	0.001	-10000	0	-10000	0	0
Gs family/GTP	0.007	0.03	-10000	0	-0.14	11	11
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	0.003	0.008	0.042	11	-10000	0	11
GNAL	0.008	0.059	-10000	0	-0.29	11	11
GNG2	0.02	0.003	-10000	0	-10000	0	0
CRH	-0.017	0.004	-10000	0	-10000	0	0
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.002	0.019	-10000	0	-0.23	2	2
MAPK11	0.003	0.001	-10000	0	-10000	0	0

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.019	0.005	-9999	-10000	0	0
SMAD2	-0.009	0.054	-9999	-0.25	5	5
SMAD3	-0.006	0.038	-9999	-10000	0	0
SMAD3/SMAD4	0.004	0.069	-9999	-0.37	8	8
SMAD4/Ubc9/PIASy	0.037	0.014	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	0.021	0.06	-9999	-0.23	5	5
PPM1A	0.02	0.003	-9999	-10000	0	0
CALM1	0.02	0.005	-9999	-10000	0	0
SMAD2/SMAD4	0	0.052	-9999	-0.24	5	5
MAP3K1	0.02	0.005	-9999	-10000	0	0
TRAP-1/SMAD4	0.027	0.021	-9999	-0.2	2	2
MAPK3	0.02	0.002	-9999	-10000	0	0
MAPK1	0.02	0.002	-9999	-10000	0	0
NUP214	0.02	0.002	-9999	-10000	0	0
CTDSP1	0.018	0.006	-9999	-10000	0	0
CTDSP2	0.02	0.002	-9999	-10000	0	0
CTDSPL	0.019	0.005	-9999	-10000	0	0
KPNB1	0.021	0.002	-9999	-10000	0	0
TGFBRAP1	0.018	0.026	-9999	-0.29	2	2
UBE2I	0.02	0.004	-9999	-10000	0	0
NUP153	0.02	0.005	-9999	-10000	0	0
KPNA2	0.02	0.004	-9999	-10000	0	0
PIAS4	0.02	0.005	-9999	-10000	0	0

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	0.025	0.012	0.19	1	-10000	0	1
EFNA5	0.02	0.005	-10000	0	-10000	0	0
FYN	-0.019	0.021	0.17	1	-0.16	4	5
neuron projection morphogenesis	0.025	0.012	0.19	1	-10000	0	1
cell-cell signaling	0	0	-10000	0	-10000	0	0
Ephrin A5/EPHA5	0.025	0.012	0.19	1	-10000	0	1
EPHA5	0.003	0.025	0.29	1	-10000	0	1

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.02	0.003	-10000	0	-10000	0	0
HDAC4	0.018	0.007	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.018	0.005	-10000	0	-10000	0	0
CDKN1A	-0.012	0.004	-10000	0	-10000	0	0
KAT2B	0.019	0.005	-10000	0	-10000	0	0
BAX	0.02	0.004	-10000	0	-10000	0	0
FOXO3	-0.002	0.003	-10000	0	-10000	0	0
FOXO1	0.017	0.026	-10000	0	-0.29	2	2
FOXO4	0.005	0.001	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.02	0.003	-10000	0	-10000	0	0
TAT	0.004	0.025	0.29	1	-10000	0	1
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.018	0.006	-10000	0	-10000	0	0
PPARGC1A	-0.001	0.078	0.29	1	-0.29	19	20
FHL2	0.018	0.026	-10000	0	-0.29	2	2
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.029	0.007	-10000	0	-10000	0	0
HIST2H4A	-0.018	0.005	-10000	0	-10000	0	0
SIRT1/FOXO3a	0.016	0.021	-10000	0	-0.2	1	1
SIRT1	0.019	0.003	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.033	0.017	-10000	0	-10000	0	0
SIRT1/Histone H1b	0.015	0.038	-10000	0	-0.22	2	2
apoptosis	-0.038	0.011	-10000	0	-10000	0	0
SIRT1/PGC1A	0.013	0.049	0.19	1	-0.17	19	20
p53/SIRT1	0.026	0.009	-10000	0	-10000	0	0
SIRT1/FOXO4	0.016	0.028	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	0.033	0.025	-10000	0	-0.15	4	4
HIST1H1E	0.007	0.016	-10000	0	-10000	0	0
SIRT1/p300	0.029	0.007	-10000	0	-10000	0	0
muscle cell differentiation	0.02	0.012	-10000	0	-10000	0	0
TP53	0.018	0.006	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0.038	0.011	-10000	0	-10000	0	0
CREBBP	0.02	0.004	-10000	0	-10000	0	0
MEF2D	0.019	0.005	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.028	0.013	0.22	1	-10000	0	1
ACSS2	-0.017	0.006	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	-0.02	0.012	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	0.036	0.052	0.24	1	-10000	0	1
Ran/GTP/Exportin 1/HDAC1	-0.02	0.004	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.014	0.061	0.21	1	-0.24	7	8
SUMO1	0.019	0.005	-10000	0	-10000	0	0
ZFPM1	0.019	0.005	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.005	0.002	-10000	0	-10000	0	0
FKBP3	0.02	0.003	-10000	0	-10000	0	0
Histones	0.039	0.047	-10000	0	-10000	0	0
YY1/LSF	0.008	0.044	-10000	0	-0.22	2	2
SMG5	0.019	0.005	-10000	0	-10000	0	0
RAN	0.02	0.002	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	0.01	0.022	0.15	2	-10000	0	2
I kappa B alpha/HDAC1	0.019	0.041	-10000	0	-10000	0	0
SAP18	0.02	0.004	-10000	0	-10000	0	0
RELA	0.012	0.031	0.16	1	-10000	0	1
HDAC1/Smad7	0.038	0.012	-10000	0	-10000	0	0
RANGAP1	0.02	0.003	-10000	0	-10000	0	0
HDAC3/TR2	0.019	0.044	-10000	0	-0.17	8	8
NuRD/MBD3 Complex	0.002	0.048	-10000	0	-0.26	2	2
NF kappa B1 p50/RelA	0.015	0.06	0.2	1	-0.24	7	8
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	0.009	0.048	-10000	0	-0.29	7	7
GATA1	0.012	0.023	0.29	1	-10000	0	1
Mad/Max	0.029	0.006	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	-0.003	0.058	-10000	0	-0.23	6	6
RBBP7	0.02	0.004	-10000	0	-10000	0	0
NPC	0.012	0.002	-10000	0	-10000	0	0
RBBP4	0.021	0.001	-10000	0	-10000	0	0
MAX	0.02	0.003	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.02	0.004	-10000	0	-10000	0	0
NFKBIA	0.011	0.013	-10000	0	-10000	0	0
KAT2B	0.019	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	-0.001	0.03	-10000	0	-10000	0	0
SIN3 complex	0.046	0.018	-10000	0	-10000	0	0
SMURF1	0.02	0.004	-10000	0	-10000	0	0
CHD3	0.019	0.006	-10000	0	-10000	0	0
SAP30	0.02	0.004	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.019	0.006	-10000	0	-10000	0	0
YY1/HDAC3	0.006	0.036	-10000	0	-0.22	1	1
YY1/HDAC2	0.009	0.044	-10000	0	-0.22	2	2
YY1/HDAC1	0.008	0.045	-10000	0	-0.22	2	2
NuRD/MBD2 Complex (MeCP1)	0.001	0.051	-10000	0	-0.3	3	3
PPARG	0	0.067	0.18	1	-0.24	15	16
HDAC8/hEST1B	0.037	0.013	-10000	0	-10000	0	0
UBE2I	0.02	0.004	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.02	0.004	-10000	0	-10000	0	0
TNFRSF1A	0.019	0.005	-10000	0	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.019	0.043	-10000	0	-0.17	8	8
MBD3L2	-0.017	0.004	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.038	0.012	-10000	0	-10000	0	0
CREBBP	0.02	0.004	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0	0.06	-10000	0	-0.26	7	7
HDAC1	0.021	0.001	-10000	0	-10000	0	0
HDAC3	0.011	0.013	-10000	0	-10000	0	0
HDAC2	0.02	0.003	-10000	0	-10000	0	0
YY1	0.006	0.003	-10000	0	-10000	0	0
HDAC8	0.02	0.002	-10000	0	-10000	0	0
SMAD7	0.02	0.004	-10000	0	-10000	0	0
NCOR2	0.021	0.002	-10000	0	-10000	0	0
MXD1	0.02	0.003	-10000	0	-10000	0	0
STAT3	0.009	0.003	-10000	0	-10000	0	0
NFKB1	0.02	0.003	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.02	0.003	-10000	0	-10000	0	0
YY1/LSF/HDAC1	0.019	0.046	-10000	0	-0.21	2	2
YY1/SAP30/HDAC1	0.018	0.047	-10000	0	-0.21	2	2
EP300	0.02	0.003	-10000	0	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.009	0.003	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.011	0.013	-10000	0	-10000	0	0
histone deacetylation	0.001	0.05	-10000	0	-0.3	3	3
STAT3 (dimer non-phopshorylated)/HDAC3	0.01	0.024	-10000	0	-10000	0	0
nuclear export	-0.037	0.013	-10000	0	-10000	0	0
PRKACA	0.02	0.004	-10000	0	-10000	0	0
GATAD2B	0.019	0.005	-10000	0	-10000	0	0
GATAD2A	0.02	0.003	-10000	0	-10000	0	0
GATA2/HDAC3	0.01	0.048	-10000	0	-0.18	1	1
GATA1/HDAC1	0.03	0.012	0.22	1	-10000	0	1
GATA1/HDAC3	0.018	0.045	0.2	1	-0.17	8	9
CHD4	0.019	0.005	-10000	0	-10000	0	0
TNF-alpha/TNFR1A	0.03	0.024	0.22	4	-10000	0	4
SIN3/HDAC complex/Mad/Max	0.006	0.04	-10000	0	-0.26	2	2
NuRD Complex	0	0.056	-10000	0	-0.26	4	4
positive regulation of chromatin silencing	0.037	0.046	-10000	0	-10000	0	0
SIN3B	0.02	0.003	-10000	0	-10000	0	0
MTA2	0.02	0.002	-10000	0	-10000	0	0
SIN3A	0.02	0.004	-10000	0	-10000	0	0
XPO1	0.02	0.003	-10000	0	-10000	0	0
SUMO1/HDAC1	0.019	0.04	-10000	0	-0.17	4	4
HDAC complex	0.05	0.013	-10000	0	-10000	0	0
GATA1/Fog1	0.028	0.014	0.22	1	-10000	0	1
FKBP25/HDAC1/HDAC2	0.04	0.009	-10000	0	-10000	0	0
TNF	0.023	0.032	0.29	4	-10000	0	4
negative regulation of cell growth	0.006	0.04	-10000	0	-0.26	2	2
NuRD/MBD2/PRMT5 Complex	0.001	0.051	-10000	0	-0.3	3	3
Ran/GTP/Exportin 1	0.018	0.039	-10000	0	-0.16	4	4
NF kappa B/RelA/I kappa B alpha	0.004	0.046	0.19	2	-0.22	5	7
SIN3/HDAC complex/NCoR1	-0.004	0.049	-10000	0	-0.25	6	6
TFCP2	0.02	0.003	-10000	0	-10000	0	0
NR2C1	0.021	0.001	-10000	0	-10000	0	0
MBD3	0.019	0.005	-10000	0	-10000	0	0
MBD2	0.02	0.005	-10000	0	-10000	0	0

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	0.02	0.004	-10000	0	-9999	0
GPC2	0.022	0.023	0.29	2	-9999	2
GPC2/Midkine	0.029	0.018	0.22	2	-9999	2
neuron projection morphogenesis	0.029	0.018	0.22	2	-9999	2

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.021	0.001	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.019	0.009	-10000	0	-10000	0	0
MDM2/SUMO1	0.018	0.04	-10000	0	-0.17	4	4
HDAC4	0.018	0.007	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	-0.021	0.008	-10000	0	-10000	0	0
SUMO1	0.019	0.005	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1	-0.001	0.025	-10000	0	-0.19	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
XPO1	-0.012	0.027	-10000	0	-0.17	3	3
EntrezGene:23636	0	0	-10000	0	-10000	0	0
RAN	0.02	0.002	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.02	0.003	-10000	0	-10000	0	0
SUMO1/HDAC4	0.021	0.031	-10000	0	-0.16	4	4
SUMO1/HDAC1	0.019	0.04	-10000	0	-0.17	4	4
RANGAP1	0.02	0.003	-10000	0	-10000	0	0
MDM2/SUMO1/SUMO1	0.045	0.019	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.005	0.002	-10000	0	-10000	0	0
Ran/GTP	0.009	0.036	-10000	0	-0.16	4	4
EntrezGene:23225	0	0	-10000	0	-10000	0	0
MDM2	0.02	0.004	-10000	0	-10000	0	0
UBE2I	0.02	0.004	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.008	0.044	0.18	7	-0.16	4	11
NPC	0.012	0.002	-10000	0	-10000	0	0
PIAS2	0.02	0.004	-10000	0	-10000	0	0
PIAS1	0.02	0.003	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	-0.021	0.017	-10000	0	-0.29	1	1
PI3K Class IB/PDE3B	0.021	0.017	0.29	1	-10000	0	1
PDE3B	0.021	0.017	0.29	1	-10000	0	1

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.004	0.035	0.14	17	-10000	0	17
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.009	0.037	0.13	12	-0.13	1	13
AP2	0.02	0.015	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.023	0.015	-10000	0	-10000	0	0
CLTB	0.02	0.004	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.008	0.005	-10000	0	-10000	0	0
CD4	0.02	0.005	-10000	0	-10000	0	0
CLTA	0.02	0.003	-10000	0	-10000	0	0
mol:GTP	-0.002	0.003	-10000	0	-10000	0	0
ARFGAP1	-0.009	0.002	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.001	0.014	-10000	0	-10000	0	0
ARF1/GTP	0.024	0.011	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	-0.004	0.007	-10000	0	-10000	0	0
mol:Choline	-0.001	0.014	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.02	0.008	-10000	0	-10000	0	0
DDEF1	0	0.014	-10000	0	-10000	0	0
ARF1/GDP	-0.001	0.018	-10000	0	-0.087	8	8
AP2M1	0.013	0.01	-10000	0	-10000	0	0
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	-0.011	0.009	-10000	0	-10000	0	0
Rac/GTP	0.016	0.006	-10000	0	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.024	0.012	-10000	0	-10000	0	0
ARFIP2	0.012	0.019	-10000	0	-10000	0	0
COPA	0.019	0.005	-10000	0	-10000	0	0
RAC1	0.02	0.003	-10000	0	-10000	0	0
ARF1/GTP/coatomer protein complex	0.004	0.018	-10000	0	-0.15	2	2
ARF1/GTP/ARHGAP10	0.013	0.006	-10000	0	-10000	0	0
GGA3	0.02	0.004	-10000	0	-10000	0	0
ARF1/GTP/Membrin	0.013	0.019	-10000	0	-0.23	1	1
AP2A1	0.02	0.004	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	-0.002	0.031	-10000	0	-0.16	10	10
ARF1/GDP/Membrin	0.015	0.022	-10000	0	-0.26	1	1
Arfaptin 2/Rac/GDP	0.021	0.017	-10000	0	-10000	0	0
CYTH2	0.023	0.008	-10000	0	-10000	0	0
ARF1/GTP/GGA3	0.026	0.011	-10000	0	-10000	0	0
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.015	0.002	-10000	0	-10000	0	0
mol:Brefeldin A	0	0	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.007	0.017	-10000	0	-0.16	1	1
PLD2	-0.001	0.014	-10000	0	-10000	0	0
ARF-GAP1/v-SNARE	-0.009	0.002	-10000	0	-10000	0	0
PIP5K1A	-0.001	0.014	-10000	0	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0.007	0.021	-10000	0	-10000	0	0
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.001	0.014	-10000	0	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	-0.009	0.002	-10000	0	-10000	0	0
GOSR2	0.006	0.02	-10000	0	-0.32	1	1
USO1	0.001	0.043	-10000	0	-0.32	5	5
GBF1	0.003	0.038	-10000	0	-0.32	4	4
ARF1/GTP/Arfaptin 2	0.023	0.016	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.026	0.021	-10000	0	-10000	0	0

×

PLK2 and PLK4 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	Mean.of.Down.Perturbations
PLK2	0.02	0.004	-9999	-9999
PLK4	0.02	0.003	-9999	-9999
regulation of centriole replication	-0.017	0.005	-9999	-9999

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.017	0.019	-9999	-10000	0	0
CLOCK	0.02	0.004	-9999	-10000	0	0
TIMELESS/CRY2	0.017	0.016	-9999	-10000	0	0
DEC1/BMAL1	0.027	0.007	-9999	-10000	0	0
ATR	0.015	0.009	-9999	-10000	0	0
NR1D1	0.004	0.004	-9999	-10000	0	0
ARNTL	0.02	0.004	-9999	-10000	0	0
TIMELESS	0.004	0.004	-9999	-10000	0	0
NPAS2	0.019	0.026	-9999	-0.29	2	2
CRY2	0.02	0.004	-9999	-10000	0	0
mol:CO	-0.002	0	-9999	-10000	0	0
CHEK1	0.017	0.008	-9999	-10000	0	0
mol:HEME	0.002	0	-9999	-10000	0	0
PER1	0.019	0.006	-9999	-10000	0	0
BMAL/CLOCK/NPAS2	0.04	0.021	-9999	-0.16	2	2
BMAL1/CLOCK	0.002	0.048	-9999	-0.33	1	1
S phase of mitotic cell cycle	0.017	0.019	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	0.018	0.019	-9999	-10000	0	0
mol:NADPH	0.002	0	-9999	-10000	0	0
PER1/TIMELESS	0.017	0.013	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	-0.009	0.015	-9999	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
ITGB1	0.02	0.003	-9999	-9999
ITGB7	0.02	0.003	-9999	-9999
ITGA4	0.02	0.004	-9999	-9999
alpha4/beta7 Integrin	0.029	0.007	-9999	-9999
alpha4/beta1 Integrin	0.029	0.007	-9999	-9999

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.01	0.013	-10000	0	-10000	0	0
regulation of axonogenesis	0.002	0.005	-10000	0	-10000	0	0
myoblast fusion	-0.027	0.039	-10000	0	-10000	0	0
mol:GTP	0.02	0.016	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.04	0.024	0.16	2	-10000	0	2
ARF1/GTP	0.028	0.018	-10000	0	-10000	0	0
mol:GM1	0.009	0.012	-10000	0	-10000	0	0
mol:Choline	-0.007	0.008	-10000	0	-10000	0	0
lamellipodium assembly	0.007	0.01	-10000	0	-10000	0	0
MAPK3	0.013	0.012	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.041	0.025	-10000	0	-0.16	2	2
ARF1	0.019	0.005	-10000	0	-10000	0	0
ARF6/GDP	0.028	0.039	-10000	0	-10000	0	0
ARF1/GDP	0.027	0.031	-10000	0	-10000	0	0
ARF6	0.03	0.019	-10000	0	-10000	0	0
RAB11A	0.02	0.003	-10000	0	-10000	0	0
TIAM1	0.018	0.027	-10000	0	-0.29	2	2
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.013	0.012	-10000	0	-10000	0	0
actin filament bundle formation	-0.026	0.029	-10000	0	-10000	0	0
KALRN	-0.001	0.032	-10000	0	-0.16	1	1
RAB11FIP3/RAB11A	0.029	0.007	-10000	0	-10000	0	0
RhoA/GDP	0.026	0.03	-10000	0	-10000	0	0
NME1	0.02	0.007	-10000	0	-10000	0	0
Rac1/GDP	0.028	0.029	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.02	0.016	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	0.007	0.01	-10000	0	-10000	0	0
RAC1	0.02	0.003	-10000	0	-10000	0	0
liver development	0.02	0.016	-10000	0	-10000	0	0
ARF6/GTP	0.02	0.016	-10000	0	-10000	0	0
RhoA/GTP	0.028	0.019	-10000	0	-10000	0	0
mol:GDP	0.006	0.006	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	0.042	0.016	-10000	0	-10000	0	0
RHOA	0.019	0.006	-10000	0	-10000	0	0
PLD1	0.006	0.009	-10000	0	-10000	0	0
RAB11FIP3	0.02	0.004	-10000	0	-10000	0	0
tube morphogenesis	0.007	0.01	-10000	0	-10000	0	0
ruffle organization	-0.002	0.005	-10000	0	-10000	0	0
regulation of epithelial cell migration	0.02	0.016	-10000	0	-10000	0	0
PLD2	0.013	0.014	-10000	0	-10000	0	0
PIP5K1A	-0.002	0.005	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.007	0.008	-10000	0	-10000	0	0
Rac1/GTP	0.007	0.01	-10000	0	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.02	0.003	-9999	-10000	0	0
Rac1/GDP	0.022	0.01	-9999	-10000	0	0
DOCK1	0.02	0.003	-9999	-10000	0	0
ITGA4	0.02	0.004	-9999	-10000	0	0
RAC1	0.02	0.003	-9999	-10000	0	0
alpha4/beta7 Integrin	0.029	0.007	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.019	0.006	-9999	-10000	0	0
alpha4/beta1 Integrin	0.038	0.012	-9999	-10000	0	0
alpha4/beta7 Integrin/Paxillin	0.028	0.008	-9999	-10000	0	0
lamellipodium assembly	-0.011	0.069	-9999	-0.4	7	7
PIK3CA	0.013	0.01	-9999	-10000	0	0
PI3K	0.019	0.015	-9999	-10000	0	0
ARF6	0.02	0.003	-9999	-10000	0	0
TLN1	0.02	0.003	-9999	-10000	0	0
PXN	-0.018	0.003	-9999	-10000	0	0
PIK3R1	0.02	0.004	-9999	-10000	0	0
ARF6/GTP	0.035	0.016	-9999	-10000	0	0
cell adhesion	0.036	0.012	-9999	-10000	0	0
CRKL/CBL	0.025	0.012	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.027	0.009	-9999	-10000	0	0
ITGB1	0.02	0.003	-9999	-10000	0	0
ITGB7	0.02	0.003	-9999	-10000	0	0
ARF6/GDP	0.022	0.01	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.033	0.034	-9999	-0.16	8	8
p130Cas/Crk/Dock1	0.037	0.014	-9999	-10000	0	0
VCAM1	0.012	0.051	-9999	-0.29	8	8
alpha4/beta1 Integrin/Paxillin/Talin	0.038	0.013	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.037	0.013	-9999	-10000	0	0
BCAR1	0.02	0.004	-9999	-10000	0	0
mol:GDP	-0.036	0.013	-9999	-10000	0	0
CBL	0.017	0.008	-9999	-10000	0	0
PRKACA	0.02	0.004	-9999	-10000	0	0
GIT1	0.02	0.003	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.038	0.013	-9999	-10000	0	0
Rac1/GTP	-0.012	0.076	-9999	-0.44	7	7

×

Atypical NF-kappaB 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.029	0.008	-10000	0	-9999	0
FBXW11	0.02	0.004	-10000	0	-9999	0
NF kappa B1 p50/c-Rel	-0.02	0.006	-10000	0	-9999	0
NF kappa B1 p50/RelA/I kappa B alpha	0.024	0.034	0.22	3	-9999	3
NFKBIA	0.001	0	-10000	0	-9999	0
MAPK14	0.02	0.003	-10000	0	-9999	0
NF kappa B1 p105/p50	-0.02	0.007	-10000	0	-9999	0
ARRB2	0.006	0.002	-10000	0	-9999	0
REL	0.02	0.003	-10000	0	-9999	0
response to oxidative stress	0	0	-10000	0	-9999	0
BCL3/NF kappa B1 p50	-0.019	0.007	-10000	0	-9999	0
response to UV	0	0	-10000	0	-9999	0
NF kappa B1 p105/RelA	-0.02	0.006	-10000	0	-9999	0
PIK3CA	0.013	0.01	-10000	0	-9999	0
NF kappa B1 p50 dimer	-0.017	0.008	-10000	0	-9999	0
PIK3R1	0.02	0.004	-10000	0	-9999	0
NFKB1	-0.017	0.005	-10000	0	-9999	0
RELA	0.02	0.003	-10000	0	-9999	0
positive regulation of anti-apoptosis	0.009	0.022	-10000	0	-9999	0
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.019	0.035	0.17	2	-9999	2
SRC	0.019	0.006	-10000	0	-9999	0
PI3K	0.019	0.015	-10000	0	-9999	0
NF kappa B1 p50/RelA	0.009	0.022	-10000	0	-9999	0
IKBKB	0.02	0.005	-10000	0	-9999	0
beta TrCP1/SCF ubiquitin ligase complex	0.02	0.004	-10000	0	-9999	0
SYK	0.02	0.003	-10000	0	-9999	0
I kappa B alpha/PIK3R1	0.024	0.037	0.23	3	-9999	3
cell death	0.018	0.034	0.16	2	-9999	2
NF kappa B1 p105/c-Rel	-0.02	0.006	-10000	0	-9999	0
LCK	0.021	0.001	-10000	0	-9999	0
BCL3	0.02	0.005	-10000	0	-9999	0

×

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
IKK alpha homodimer	0.03	0.006	-9999	-9999
FBXW11	0.02	0.004	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-9999
beta TrCP1/SCF ubiquitin ligase complex	0.02	0.004	-9999	-9999
CHUK	0.02	0.003	-9999	-9999
NF kappa B2 p100/RelB	0.053	0.022	-9999	-9999
NFKB1	0.02	0.003	-9999	-9999
MAP3K14	0.02	0.002	-9999	-9999
NF kappa B1 p50/RelB	0.029	0.008	-9999	-9999
RELB	0.02	0.004	-9999	-9999
NFKB2	0.02	0.003	-9999	-9999
NF kappa B2 p52/RelB	0.026	0.007	-9999	-9999
regulation of B cell activation	0.026	0.007	-9999	-9999

pid_entity	TCGA.ZX.AA5X	TCGA.ZJ.AB0I	TCGA.ZJ.AB0H	TCGA.ZJ.AAXU
109_MAP3K5	0.0056	-0.14	0.0056	0.0056
47_PPARGC1A	0.021	0	0.021	0.021
105_BMP4	0.021	0.021	0.021	0.021
105_BMP6	0.021	0.021	0.021	0.021
105_BMP7	0.021	0.021	0.021	0.021
105_BMP2	0.021	0.021	0.021	0.021
131_RELN/VLDLR	0.053	-0.12	-0.16	0.053
30_TGFB1/TGF beta receptor Type II	0.021	0.021	0.021	0.021
84_STAT5B	-0.067	-0.35	-0.063	-0.099
84_STAT5A	-0.067	-0.35	-0.063	-0.099