PARADIGM pathway analysis of mRNASeq expression and copy number data - Glioblastoma Multiforme (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
Glypican 2 network	56
Aurora B signaling	30
TCGA08_p53	28
TCGA08_retinoblastoma	26
Aurora C signaling	21
Ceramide signaling pathway	19
Effects of Botulinum toxin	17
Arf6 signaling events	15
EPO signaling pathway	15
LPA4-mediated signaling events	14

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
Glypican 2 network	0.3660	56	226	4	-0.03	0.037	1000	-1000	0.021	-1000
Aurora B signaling	0.1961	30	2073	67	-0.066	0.11	1000	-1000	-0.029	-1000
TCGA08_p53	0.1830	28	199	7	-0.02	0.023	1000	-1000	-0.011	-1000
TCGA08_retinoblastoma	0.1699	26	214	8	-0.071	0.08	1000	-1000	-0.002	-1000
Aurora C signaling	0.1373	21	153	7	-0.056	0.063	1000	-1000	-0.006	-1000
Ceramide signaling pathway	0.1242	19	1512	76	-0.14	0.048	1000	-1000	-0.026	-1000
Effects of Botulinum toxin	0.1111	17	457	26	-0.014	0.025	1000	-1000	-0.01	-1000
Arf6 signaling events	0.0980	15	985	62	-0.007	0.091	1000	-1000	-0.025	-1000
EPO signaling pathway	0.0980	15	829	55	-0.004	0.043	1000	-1000	-0.031	-1000
LPA4-mediated signaling events	0.0915	14	172	12	-0.017	0.005	1000	-1000	-0.016	-1000
Signaling events mediated by the Hedgehog family	0.0915	14	776	52	-0.016	0.055	1000	-1000	-0.024	-1000
a4b1 and a4b7 Integrin signaling	0.0915	14	73	5	0.013	0.041	1000	-1000	0.022	-1000
Retinoic acid receptors-mediated signaling	0.0850	13	798	58	-0.22	0.048	1000	-1000	-0.04	-1000
IL2 signaling events mediated by STAT5	0.0850	13	297	22	-0.036	0.052	1000	-1000	-0.033	-1000
Rapid glucocorticoid signaling	0.0850	13	262	20	-0.007	0.031	1000	-1000	-0.011	-1000
Syndecan-1-mediated signaling events	0.0784	12	441	34	-0.043	0.033	1000	-1000	-0.022	-1000
JNK signaling in the CD4+ TCR pathway	0.0784	12	211	17	-0.33	0.046	1000	-1000	-0.022	-1000
PLK1 signaling events	0.0784	12	1023	85	-0.056	0.065	1000	-1000	-0.021	-1000
Signaling events regulated by Ret tyrosine kinase	0.0719	11	973	82	-0.073	0.032	1000	-1000	-0.036	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0719	11	945	83	-0.16	0.16	1000	-1000	-0.023	-1000
Ephrin A reverse signaling	0.0654	10	75	7	-0.017	0.029	1000	-1000	-0.012	-1000
TCGA08_rtk_signaling	0.0654	10	267	26	-0.045	0.13	1000	-1000	-0.004	-1000
LPA receptor mediated events	0.0654	10	1055	102	-0.043	0.039	1000	-1000	-0.053	-1000
EGFR-dependent Endothelin signaling events	0.0654	10	220	21	-0.012	0.038	1000	-1000	-0.028	-1000
Syndecan-4-mediated signaling events	0.0654	10	688	67	-0.045	0.04	1000	-1000	-0.03	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0654	10	357	33	-0.056	0.049	1000	-1000	-0.025	-1000
S1P4 pathway	0.0654	10	268	25	0	0.048	1000	-1000	-0.014	-1000
Alternative NF-kappaB pathway	0.0654	10	142	13	0	0.044	1000	-1000	0	-1000
amb2 Integrin signaling	0.0588	9	780	82	-0.043	0.071	1000	-1000	-0.018	-1000
Caspase cascade in apoptosis	0.0523	8	609	74	-0.062	0.065	1000	-1000	-0.029	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0523	8	693	85	-0.051	0.11	1000	-1000	-0.042	-1000
Nectin adhesion pathway	0.0523	8	563	63	-0.019	0.06	1000	-1000	-0.032	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0523	8	331	37	-0.034	0.061	1000	-1000	-0.02	-1000
FAS signaling pathway (CD95)	0.0523	8	402	47	-0.17	0.037	1000	-1000	-0.029	-1000
Arf6 trafficking events	0.0523	8	582	71	-0.043	0.045	1000	-1000	-0.037	-1000
Thromboxane A2 receptor signaling	0.0458	7	752	105	-0.066	0.034	1000	-1000	-0.047	-1000
HIF-1-alpha transcription factor network	0.0458	7	575	76	-0.076	0.13	1000	-1000	-0.037	-1000
IL2 signaling events mediated by PI3K	0.0458	7	420	58	-0.22	0.037	1000	-1000	-0.042	-1000
Calcium signaling in the CD4+ TCR pathway	0.0458	7	232	31	-0.03	0.026	1000	-1000	-0.029	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0458	7	482	68	-0.062	0.052	1000	-1000	-0.062	-1000
Signaling events mediated by PRL	0.0458	7	247	34	-0.025	0.045	1000	-1000	-0.027	-1000
Aurora A signaling	0.0392	6	401	60	-0.056	0.07	1000	-1000	-0.022	-1000
BMP receptor signaling	0.0392	6	524	81	-0.027	0.049	1000	-1000	-0.018	-1000
Glucocorticoid receptor regulatory network	0.0392	6	728	114	-0.18	0.11	1000	-1000	-0.051	-1000
Canonical Wnt signaling pathway	0.0392	6	329	51	-0.013	0.11	1000	-1000	-0.031	-1000
E-cadherin signaling in keratinocytes	0.0392	6	275	43	-0.019	0.074	1000	-1000	-0.018	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0392	6	518	78	-0.023	0.061	1000	-1000	-0.049	-1000
BARD1 signaling events	0.0327	5	331	57	-0.061	0.076	1000	-1000	-0.046	-1000
Cellular roles of Anthrax toxin	0.0327	5	199	39	-0.023	0.037	1000	-1000	-0.017	-1000
Signaling events mediated by PTP1B	0.0327	5	452	76	-0.038	0.075	1000	-1000	-0.023	-1000
Arf6 downstream pathway	0.0327	5	236	43	-0.038	0.039	1000	-1000	-0.031	-1000
Glypican 1 network	0.0327	5	276	48	-0.03	0.051	1000	-1000	-0.022	-1000
Fc-epsilon receptor I signaling in mast cells	0.0327	5	508	97	-0.12	0.095	1000	-1000	-0.04	-1000
Insulin-mediated glucose transport	0.0327	5	177	32	-0.056	0.051	1000	-1000	-0.021	-1000
mTOR signaling pathway	0.0327	5	312	53	-0.022	0.055	1000	-1000	-0.034	-1000
Reelin signaling pathway	0.0327	5	300	56	-0.069	0.044	1000	-1000	-0.024	-1000
IL1-mediated signaling events	0.0327	5	312	62	-0.054	0.074	1000	-1000	-0.041	-1000
Endothelins	0.0327	5	564	96	-0.12	0.044	1000	-1000	-0.044	-1000
TCR signaling in naïve CD8+ T cells	0.0327	5	521	93	-0.34	0.38	1000	-1000	-0.032	-1000
EPHB forward signaling	0.0327	5	446	85	-0.049	0.071	1000	-1000	-0.041	-1000
Regulation of p38-alpha and p38-beta	0.0327	5	285	54	-0.008	0.046	1000	-1000	-0.038	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0327	5	708	125	-0.043	0.097	1000	-1000	-0.038	-1000
E-cadherin signaling in the nascent adherens junction	0.0327	5	398	76	-0.037	0.069	1000	-1000	-0.038	-1000
BCR signaling pathway	0.0327	5	495	99	-0.046	0.08	1000	-1000	-0.04	-1000
IL23-mediated signaling events	0.0327	5	312	60	-0.18	0.058	1000	-1000	-0.12	-1000
Plasma membrane estrogen receptor signaling	0.0327	5	436	86	-0.035	0.047	1000	-1000	-0.041	-1000
PDGFR-beta signaling pathway	0.0327	5	519	97	-0.04	0.083	1000	-1000	-0.038	-1000
Visual signal transduction: Rods	0.0327	5	266	52	-0.035	0.075	1000	-1000	-0.037	-1000
p38 MAPK signaling pathway	0.0327	5	225	44	0	0.05	1000	-1000	-0.015	-1000
Ras signaling in the CD4+ TCR pathway	0.0327	5	97	17	-0.067	0.044	1000	-1000	-0.019	-1000
IL12-mediated signaling events	0.0261	4	409	87	-0.067	0.063	1000	-1000	-0.076	-1000
Visual signal transduction: Cones	0.0261	4	176	38	-0.021	0.056	1000	-1000	-0.02	-1000
Osteopontin-mediated events	0.0261	4	186	38	-0.063	0.067	1000	-1000	-0.026	-1000
Syndecan-2-mediated signaling events	0.0261	4	311	69	-0.027	0.045	1000	-1000	-0.025	-1000
p75(NTR)-mediated signaling	0.0261	4	558	125	-0.045	0.075	1000	-1000	-0.045	-1000
IFN-gamma pathway	0.0261	4	303	68	-0.12	0.049	1000	-1000	-0.038	-1000
Class I PI3K signaling events mediated by Akt	0.0261	4	331	68	-0.025	0.048	1000	-1000	-0.021	-1000
HIF-2-alpha transcription factor network	0.0261	4	194	43	-0.043	0.048	1000	-1000	-0.04	-1000
Ephrin B reverse signaling	0.0261	4	207	48	-0.022	0.05	1000	-1000	-0.03	-1000
S1P1 pathway	0.0261	4	162	36	-0.02	0.042	1000	-1000	-0.028	-1000
Integrins in angiogenesis	0.0261	4	336	84	-0.053	0.069	1000	-1000	-0.041	-1000
Nongenotropic Androgen signaling	0.0261	4	253	52	-0.028	0.051	1000	-1000	-0.021	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0261	4	123	27	-0.027	0.056	1000	-1000	-0.023	-1000
Class I PI3K signaling events	0.0261	4	348	73	-0.025	0.053	1000	-1000	-0.031	-1000
S1P3 pathway	0.0261	4	176	42	0	0.041	1000	-1000	-0.021	-1000
FOXM1 transcription factor network	0.0261	4	210	51	-0.016	0.073	1000	-1000	-0.16	-1000
Arf1 pathway	0.0261	4	264	54	-0.084	0.047	1000	-1000	-0.012	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0196	3	88	28	-0.021	0.035	1000	-1000	-0.02	-1000
PDGFR-alpha signaling pathway	0.0196	3	149	44	-0.021	0.054	1000	-1000	-0.021	-1000
TRAIL signaling pathway	0.0196	3	153	48	-0.049	0.071	1000	-1000	-0.02	-1000
S1P5 pathway	0.0196	3	64	17	-0.028	0.029	1000	-1000	-0.001	-1000
ceramide signaling pathway	0.0196	3	161	49	-0.015	0.048	1000	-1000	-0.027	-1000
FoxO family signaling	0.0196	3	242	64	-0.075	0.047	1000	-1000	-0.071	-1000
Atypical NF-kappaB pathway	0.0196	3	112	31	-0.025	0.036	1000	-1000	-0.022	-1000
Syndecan-3-mediated signaling events	0.0196	3	125	35	0	0.063	1000	-1000	-0.023	-1000
Signaling mediated by p38-alpha and p38-beta	0.0196	3	132	44	-0.025	0.064	1000	-1000	-0.017	-1000
IL6-mediated signaling events	0.0196	3	244	75	-0.001	0.11	1000	-1000	-0.066	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0196	3	229	74	-0.1	0.061	1000	-1000	-0.04	-1000
Insulin Pathway	0.0196	3	288	74	-0.062	0.067	1000	-1000	-0.037	-1000
VEGFR1 specific signals	0.0196	3	192	56	-0.037	0.05	1000	-1000	-0.024	-1000
ErbB2/ErbB3 signaling events	0.0131	2	139	65	-0.041	0.038	1000	-1000	-0.05	-1000
Regulation of nuclear SMAD2/3 signaling	0.0131	2	398	136	-0.2	0.079	1000	-1000	-0.031	-1000
Coregulation of Androgen receptor activity	0.0131	2	218	76	-0.02	0.053	1000	-1000	-0.018	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0131	2	48	23	-0.019	0.048	1000	-1000	-0.014	-1000
Signaling events mediated by HDAC Class II	0.0131	2	183	75	-0.026	0.07	1000	-1000	-0.021	-1000
PLK2 and PLK4 events	0.0131	2	7	3	-0.021	-1000	1000	-1000	-0.02	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0131	2	134	54	-0.037	0.037	1000	-1000	-0.032	-1000
Hedgehog signaling events mediated by Gli proteins	0.0131	2	156	65	-0.001	0.065	1000	-1000	-0.036	-1000
Presenilin action in Notch and Wnt signaling	0.0131	2	173	61	0	0.063	1000	-1000	-0.039	-1000
IL4-mediated signaling events	0.0131	2	189	91	-0.28	0.082	1000	-1000	-0.15	-1000
Signaling events mediated by HDAC Class III	0.0131	2	97	40	-0.035	0.036	1000	-1000	-0.042	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0131	2	116	52	-0.012	0.069	1000	-1000	-0.028	-1000
Signaling events mediated by HDAC Class I	0.0131	2	237	104	-0.049	0.057	1000	-1000	-0.041	-1000
Paxillin-dependent events mediated by a4b1	0.0131	2	100	36	-0.03	0.041	1000	-1000	-0.025	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0131	2	126	45	-0.062	0.051	1000	-1000	-0.043	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0131	2	340	120	-0.035	0.068	1000	-1000	-0.04	-1000
Canonical NF-kappaB pathway	0.0065	1	73	39	-0.025	0.054	1000	-1000	-0.016	-1000
ErbB4 signaling events	0.0065	1	103	69	-0.024	0.039	1000	-1000	-0.025	-1000
Noncanonical Wnt signaling pathway	0.0065	1	42	26	-0.015	0.041	1000	-1000	-0.023	-1000
FOXA2 and FOXA3 transcription factor networks	0.0065	1	80	46	-0.065	0.037	1000	-1000	-0.1	-1000
Signaling mediated by p38-gamma and p38-delta	0.0065	1	17	15	-0.024	0.026	1000	-1000	-0.022	-1000
IL27-mediated signaling events	0.0065	1	66	51	-0.011	0.044	1000	-1000	-0.047	-1000
Wnt signaling	0.0065	1	8	7	0.011	0.025	1000	-1000	-0.008	-1000
Regulation of Telomerase	0.0065	1	137	102	-0.025	0.067	1000	-1000	-0.046	-1000
IGF1 pathway	0.0065	1	74	57	-0.047	0.071	1000	-1000	-0.034	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0065	1	164	88	-0.032	0.039	1000	-1000	-0.058	-1000
E-cadherin signaling events	0.0065	1	9	5	0.025	0.05	1000	-1000	0.021	-1000
Regulation of Androgen receptor activity	0.0065	1	130	70	-0.047	0.04	1000	-1000	-0.031	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0000	0	31	34	-0.034	0.066	1000	-1000	-0.033	-1000
Circadian rhythm pathway	0.0000	0	2	22	-0.003	0.051	1000	-1000	-0.023	-1000
Class IB PI3K non-lipid kinase events	0.0000	0	0	3	-0.025	0.026	1000	-1000	-0.022	-1000
Total	NA	847	43832	7203	-6.6	-990	131000	-131000	-4.1	-131000

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.03	0.04	-10000	0	-0.058	96	96
GPC2	0.009	0.026	-10000	0	-0.058	16	16
GPC2/Midkine	0.037	0.028	0.082	8	0	49	57
neuron projection morphogenesis	0.037	0.028	0.081	8	0	49	57

×

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	0.005	0.032	-10000	0	-0.12	8	8
STMN1	-0.044	0.01	-10000	0	-0.047	138	138
Aurora B/RasGAP/Survivin	0.086	0.026	0.092	127	-0.073	3	130
Chromosomal passenger complex/Cul3 protein complex	-0.028	0.05	0.094	1	-0.13	6	7
BIRC5	-0.045	0.039	0.059	16	-0.06	127	143
DES	0.023	0.13	-10000	0	-0.58	6	6
Aurora C/Aurora B/INCENP	0.062	0.026	0.09	1	-0.047	6	7
Aurora B/TACC1	0.051	0.017	0.062	4	-0.026	6	10
Aurora B/PP2A	0.058	0.012	0.068	5	0	6	11
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	0.001	0.017	-10000	0	-0.14	2	2
mitotic metaphase/anaphase transition	-0.002	0.002	0.013	2	-10000	0	2
NDC80	-0.066	0.018	-10000	0	-0.071	137	137
Cul3 protein complex	0.034	0.025	-10000	0	-10000	0	0
KIF2C	0.01	0.03	-10000	0	-0.31	1	1
PEBP1	0.023	0.008	-10000	0	-0.023	3	3
KIF20A	-0.055	0.023	0.063	4	-0.06	139	143
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.058	0.011	0.067	3	-10000	0	3
SEPT1	0.026	0.003	-10000	0	-10000	0	0
SMC2	0.025	0.004	-10000	0	-10000	0	0
SMC4	0.019	0.023	-10000	0	-0.058	12	12
NSUN2/NPM1/Nucleolin	0.007	0.087	-10000	0	-0.56	3	3
PSMA3	0.025	0.006	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.002	0.002	0.01	1	-10000	0	1
H3F3B	0.009	0.004	0.021	1	-0.009	5	6
AURKB	-0.05	0.033	0.065	7	-0.061	132	139
AURKC	0.023	0.015	-10000	0	-0.058	4	4
CDCA8	-0.033	0.042	0.058	10	-0.06	103	113
cytokinesis	0.001	0.051	-10000	0	-0.3	3	3
Aurora B/Septin1	0.041	0.067	0.36	1	-0.29	3	4
AURKA	-0.001	0.039	0.061	2	-0.06	42	44
INCENP	0.024	0.006	-10000	0	-0.025	2	2
KLHL13	0.026	0.002	-10000	0	-10000	0	0
BUB1	-0.052	0.029	0.065	6	-0.06	136	142
hSgo1/Aurora B/Survivin	0.099	0.027	0.1	138	-0.092	2	140
EVI5	0.025	0.006	-10000	0	-0.023	1	1
RhoA/GTP	0.049	0.047	-10000	0	-0.16	3	3
SGOL1	-0.055	0.016	-10000	0	-0.058	141	141
CENPA	0.011	0.035	-10000	0	-0.17	3	3
NCAPG	-0.058	0.007	-10000	0	-0.058	146	146
Aurora B/HC8 Proteasome	0.056	0.016	0.068	5	0	11	16
NCAPD2	0.025	0.005	-10000	0	-10000	0	0
Aurora B/PP1-gamma	0.058	0.011	0.066	6	0	5	11
RHOA	0.026	0.002	-10000	0	-10000	0	0
NCAPH	-0.036	0.037	-10000	0	-0.058	108	108
NPM1	0.002	0.084	-10000	0	-0.42	4	4
RASA1	0.026	0.004	-10000	0	-10000	0	0
KLHL9	0.017	0.012	-10000	0	-10000	0	0
mitotic prometaphase	-0.003	0.001	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.056	0.016	0.068	5	0	11	16
PPP1CC	0.026	0.003	-10000	0	-10000	0	0
Centraspindlin	0.043	0.046	-10000	0	-0.17	3	3
RhoA/GDP	0.019	0.002	-10000	0	0	1	1
NSUN2	0.003	0.085	-10000	0	-0.43	4	4
MYLK	0.009	0.004	0.021	1	-0.009	5	6
KIF23	-0.042	0.037	0.059	8	-0.059	119	127
VIM	-0.039	0.028	-10000	0	-0.056	101	101
RACGAP1	0.025	0.008	-10000	0	-0.024	2	2
mitosis	0	0	-10000	0	-10000	0	0
NCL	0.008	0.046	-10000	0	-0.31	3	3
Chromosomal passenger complex	-0.001	0.029	-10000	0	-0.14	4	4
Chromosomal passenger complex/EVI5	0.11	0.05	0.2	3	-0.094	6	9
TACC1	0.026	0.004	-10000	0	-10000	0	0
PPP2R5D	0.026	0.004	-10000	0	-10000	0	0
CUL3	0.026	0	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.013	0.016	0	86	-0.036	47	133
TP53	-0.02	0.061	-10000	0	-0.18	18	18
Senescence	-0.02	0.061	-10000	0	-0.18	18	18
Apoptosis	-0.02	0.061	-10000	0	-0.18	18	18
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.022	0.088	0.32	12	-10000	0	12
MDM4	0.023	0.009	-10000	0	-10000	0	0

×

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	0.012	0.025	0.069	6	-0.059	5	11
CDKN2C	0.015	0.041	0.072	24	-0.053	23	47
CDKN2A	0.014	0.038	0.072	26	-0.067	11	37
CCND2	0.005	0.018	0.072	3	-0.11	1	4
RB1	-0.071	0.09	0.12	1	-0.19	51	52
CDK4	0.005	0.021	0.088	4	-0.14	1	5
CDK6	0.006	0.021	0.092	4	-0.12	1	5
G1/S progression	0.08	0.098	0.21	52	-0.12	1	53

×

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.026	0.002	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	0.063	0.025	-9999	-0.045	6	6
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.007	0.027	-9999	-0.33	1	1
AURKB	-0.056	0.013	-9999	-0.058	142	142
AURKC	0.023	0.015	-9999	-0.058	4	4

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	-0.014	0.011	0	54	-10000	0	54
MAP4K4	-0.003	0.044	-10000	0	-0.29	2	2
BAG4	0.026	0.004	-10000	0	-10000	0	0
PKC zeta/ceramide	-0.057	0.12	-10000	0	-0.2	50	50
NFKBIA	0.025	0.006	-10000	0	-10000	0	0
BIRC3	0.024	0.012	-10000	0	-0.058	3	3
BAX	-0.029	0.082	-10000	0	-0.36	6	6
RIPK1	0.025	0.005	-10000	0	-10000	0	0
AKT1	0	0.057	0.66	1	-10000	0	1
BAD	-0.072	0.12	-10000	0	-0.2	52	52
SMPD1	-0.002	0.037	0.1	7	-0.14	4	11
RB1	-0.07	0.12	0.2	1	-0.2	52	53
FADD/Caspase 8	0.001	0.046	-10000	0	-0.31	2	2
MAP2K4	-0.073	0.11	0.18	1	-0.2	52	53
NSMAF	0.025	0.004	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.072	0.11	0.18	2	-0.2	52	54
EGF	0.026	0.002	-10000	0	0	1	1
mol:ceramide	-0.069	0.12	-10000	0	-0.21	52	52
MADD	0.026	0.004	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.014	0.011	0	54	-10000	0	54
ASAH1	0.025	0.005	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.07	0.12	0.2	1	-0.2	52	53
cell proliferation	-0.048	0.1	-10000	0	-0.18	47	47
BID	-0.02	0.14	-10000	0	-0.71	5	5
MAP3K1	-0.07	0.12	0.2	1	-0.2	52	53
EIF2A	-0.076	0.11	0.17	1	-0.2	52	53
TRADD	0.026	0.003	-10000	0	-10000	0	0
CRADD	0.025	0.004	-10000	0	-10000	0	0
MAPK3	-0.067	0.098	0.17	1	-0.19	46	47
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.071	0.1	0.17	1	-0.2	46	47
Cathepsin D/ceramide	-0.056	0.13	-10000	0	-0.2	52	52
FADD	-0.001	0.037	-10000	0	-0.29	1	1
KSR1	-0.07	0.12	0.2	1	-0.2	52	53
MAPK8	-0.14	0.16	0.18	1	-0.31	53	54
PRKRA	-0.072	0.12	-10000	0	-0.2	52	52
PDGFA	0.017	0.012	-10000	0	-10000	0	0
TRAF2	0.025	0.005	-10000	0	-10000	0	0
IGF1	0.026	0.004	-10000	0	-10000	0	0
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.069	0.12	-10000	0	-0.21	52	52
CTSD	0.025	0.006	-10000	0	-10000	0	0
regulation of nitric oxide biosynthetic process	0.038	0.005	-10000	0	0	3	3
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.051	0.11	-10000	0	-0.2	47	47
PRKCD	0.026	0.002	-10000	0	-10000	0	0
PRKCZ	0.019	0.011	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.014	0.011	0	54	-10000	0	54
RelA/NF kappa B1	0.038	0.005	-10000	0	0	3	3
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.025	0.006	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.003	0.043	-10000	0	-0.3	2	2
TNFR1A/BAG4/TNF-alpha	0.048	0.016	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	-0.014	0.011	0	54	-10000	0	54
MAP2K1	-0.074	0.11	0.17	2	-0.2	51	53
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.026	0.003	-10000	0	-10000	0	0
CYCS	-0.018	0.062	-10000	0	-0.18	13	13
TNFRSF1A	0.025	0.005	-10000	0	-10000	0	0
NFKB1	0.026	0.002	-10000	0	-10000	0	0
TNFR1A/BAG4	0.036	0.009	-10000	0	0	9	9
EIF2AK2	-0.075	0.11	-10000	0	-0.2	52	52
TNF-alpha/TNFR1A/FAN	0.048	0.016	-10000	0	-10000	0	0
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.02	0.045	-10000	0	-0.44	1	1
MAP2K2	-0.068	0.099	0.17	3	-0.19	49	52
SMPD3	-0.014	0.066	0.11	1	-0.2	15	16
TNF	0.025	0.005	-10000	0	-10000	0	0
PKC zeta/PAR4	0.027	0.018	-10000	0	0	43	43
mol:PHOSPHOCHOLINE	-0.043	0.075	0.13	1	-0.14	49	50
NF kappa B1/RelA/I kappa B alpha	0.045	0.046	-10000	0	-10000	0	0
AIFM1	-0.046	0.081	-10000	0	-0.14	43	43
BCL2	0.025	0.005	-10000	0	-10000	0	0

×

Effects of Botulinum toxin

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
STX1A	-0.005	0.005	0	81	-10000	0	81
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.017	0.019	-10000	0	0	83	83
STXBP1	0.021	0.01	-10000	0	-10000	0	0
ACh/CHRNA1	0.006	0.055	0.084	21	-0.055	60	81
RAB3GAP2/RIMS1/UNC13B	0.023	0.026	-10000	0	-10000	0	0
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	0.012	0.013	-10000	0	-10000	0	0
mol:ACh	-0.002	0.053	0.095	22	-0.062	15	37
RAB3GAP2	0.025	0.005	-10000	0	-10000	0	0
STX1A/SNAP25/VAMP2	-0.014	0.046	-10000	0	-0.09	12	12
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	0.006	0.055	0.084	21	-0.055	60	81
UNC13B	0.024	0.008	-10000	0	-10000	0	0
CHRNA1	-0.005	0.04	-10000	0	-0.058	53	53
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	0.006	0.021	0.067	9	-0.057	5	14
SNAP25	0.001	0.001	-10000	0	-10000	0	0
VAMP2	0.002	0	-10000	0	0	3	3
SYT1	0.007	0.012	-10000	0	-10000	0	0
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.009	0.011	-10000	0	-10000	0	0
STX1A/SNAP25 fragment 1/VAMP2	-0.014	0.046	-10000	0	-0.09	12	12

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.02	0.018	-10000	0	0	64	64
ARNO/beta Arrestin1-2	0.024	0.13	-10000	0	-0.74	4	4
EGFR	0.007	0.016	-10000	0	-0.058	4	4
EPHA2	0.024	0.011	-10000	0	-0.058	2	2
USP6	0.026	0.004	-10000	0	-10000	0	0
IQSEC1	0.026	0.002	-10000	0	-10000	0	0
EGFR/EGFR/EGF/EGF	0.015	0.02	-10000	0	0	94	94
ARRB2	0.008	0.002	-10000	0	0	3	3
mol:GTP	0	0.042	0.11	1	-0.14	4	5
ARRB1	0.026	0	-10000	0	-10000	0	0
FBXO8	0.025	0.005	-10000	0	-10000	0	0
TSHR	0.007	0.033	-10000	0	-0.058	29	29
EGF	0.026	0.002	-10000	0	0	1	1
somatostatin receptor activity	0	0	0.001	50	0	3	53
ARAP2	0.026	0.002	-10000	0	-10000	0	0
mol:GDP	0.071	0.081	0.18	44	-0.16	2	46
mol:PI-3-4-5-P3	0	0	0.001	36	-0.001	2	38
ITGA2B	0.026	0.003	-10000	0	-10000	0	0
ARF6	0.025	0.006	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.06	0.023	-10000	0	-0.028	4	4
ADAP1	0.015	0.013	-10000	0	-10000	0	0
KIF13B	0.026	0.004	-10000	0	-10000	0	0
HGF/MET	0.023	0.019	-10000	0	0	60	60
PXN	0.026	0.003	-10000	0	-10000	0	0
ARF6/GTP	0.085	0.11	0.22	47	-0.19	4	51
EGFR/EGFR/EGF/EGF/ARFGEP100	0.019	0.026	-10000	0	-10000	0	0
ADRB2	0.026	0.003	-10000	0	-10000	0	0
receptor agonist activity	0	0	0	29	0	4	33
actin filament binding	0	0	0	48	0	3	51
SRC	0.024	0.007	-10000	0	-10000	0	0
ITGB3	-0.003	0.04	-10000	0	-0.058	50	50
GNAQ	0.026	0.005	-10000	0	-10000	0	0
EFA6/PI-4-5-P2	0.001	0.001	0.002	51	-0.001	2	53
ARF6/GDP	0.006	0.1	0.17	5	-0.35	7	12
ARF6/GDP/GULP/ACAP1	0.091	0.077	0.2	35	-0.16	2	37
alphaIIb/beta3 Integrin/paxillin/GIT1	0.07	0.02	-10000	0	-0.029	1	1
ACAP1	0.026	0.004	-10000	0	-10000	0	0
ACAP2	0.025	0.005	-10000	0	-10000	0	0
LHCGR/beta Arrestin2	0.019	0.014	-10000	0	-0.073	3	3
EFNA1	0.025	0.004	-10000	0	-10000	0	0
HGF	0.018	0.012	-10000	0	-10000	0	0
CYTH3	-0.007	0.005	0	49	-10000	0	49
CYTH2	-0.006	0.15	-10000	0	-0.92	4	4
NCK1	0.026	0.004	-10000	0	-10000	0	0
fibronectin binding	0	0	0	45	0	3	48
endosomal lumen acidification	0	0	0	51	0	3	54
microtubule-based process	0	0	-10000	0	0	3	3
GULP1	0.025	0.004	-10000	0	-10000	0	0
GNAQ/ARNO	0.01	0.14	-10000	0	-0.85	4	4
mol:Phosphatidic acid	0	0	0	14	-10000	0	14
PIP3-E	0	0	0	33	-10000	0	33
MET	0.016	0.013	-10000	0	-10000	0	0
GNA14	0.025	0.005	-10000	0	-10000	0	0
GNA15	0.025	0.006	-10000	0	-10000	0	0
GIT1	0.026	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0.001	0.001	49	-0.001	2	51
GNA11	0.025	0.006	-10000	0	-10000	0	0
LHCGR	0.022	0.007	-10000	0	-0.058	1	1
AGTR1	0.016	0.027	-10000	0	-0.058	17	17
desensitization of G-protein coupled receptor protein signaling pathway	0.019	0.014	-10000	0	-0.073	3	3
IPCEF1/ARNO	-0.005	0.13	-10000	0	-0.75	4	4
alphaIIb/beta3 Integrin	0.045	0.011	-10000	0	0	2	2

×

EPO signaling pathway

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
BCL2L1	0.04	0.048	0.23	3	-10000	0	3
CRKL	0.019	0.091	0.16	37	-10000	0	37
mol:DAG	0.01	0.016	0.13	1	-10000	0	1
HRAS	0.02	0.098	0.22	16	-10000	0	16
MAPK8	0.007	0.066	0.15	24	-10000	0	24
RAP1A	0.018	0.086	0.15	38	-10000	0	38
GAB1	0.02	0.092	0.16	38	-10000	0	38
MAPK14	0.026	0.085	0.15	46	-10000	0	46
EPO	0.006	0.029	0.071	1	-0.062	16	17
PLCG1	0.011	0.016	0.13	1	-10000	0	1
EPOR/TRPC2/IP3 Receptors	0.028	0.016	0.086	2	-10000	0	2
RAPGEF1	0.025	0.006	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.037	0.028	-10000	0	-10000	0	0
GAB1/SHC/GRB2/SOS1	0.02	0.1	0.16	46	-10000	0	46
EPO/EPOR (dimer)	0.028	0.023	-10000	0	-0.028	1	1
IRS2	0.016	0.085	0.15	36	-10000	0	36
STAT1	0.013	0.018	0.14	1	-10000	0	1
STAT5B	0.011	0.017	0.14	1	-10000	0	1
cell proliferation	0.006	0.071	0.16	24	-10000	0	24
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.004	0.071	0.11	40	-10000	0	40
TEC	0.018	0.089	0.16	37	-10000	0	37
SOCS3	0.025	0.007	-10000	0	-0.058	1	1
STAT1 (dimer)	0.013	0.018	0.14	1	-10000	0	1
JAK2	0.028	0.014	0.078	3	-10000	0	3
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.043	0.04	0.21	1	-10000	0	1
EPO/EPOR	0.028	0.023	-10000	0	-0.028	1	1
LYN	0.026	0.004	-10000	0	-10000	0	0
TEC/VAV2	0.003	0.069	0.13	31	-10000	0	31
elevation of cytosolic calcium ion concentration	0.028	0.016	0.086	2	-10000	0	2
SHC1	0.023	0.013	-10000	0	-0.058	3	3
EPO/EPOR (dimer)/LYN	0.038	0.029	-10000	0	-10000	0	0
mol:IP3	0.01	0.016	0.13	1	-10000	0	1
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.023	0.099	0.16	47	-10000	0	47
SH2B3	0.029	0.014	0.064	1	-10000	0	1
NFKB1	0.026	0.086	0.15	47	-10000	0	47
EPO/EPOR (dimer)/JAK2/SOCS3	0.008	0.018	-10000	0	-0.13	2	2
PTPN6	0.028	0.086	0.15	46	-10000	0	46
TEC/VAV2/GRB2	0.004	0.076	0.14	32	-10000	0	32
EPOR	0.028	0.016	0.086	2	-10000	0	2
INPP5D	0.026	0	-10000	0	-10000	0	0
mol:GDP	0.02	0.1	0.16	46	-10000	0	46
SOS1	0.026	0	-10000	0	-10000	0	0
PLCG2	0.025	0.005	-10000	0	-10000	0	0
CRKL/CBL/C3G	0.005	0.079	0.14	33	-10000	0	33
VAV2	0.019	0.091	0.16	37	-10000	0	37
CBL	0.02	0.092	0.16	39	-10000	0	39
SHC/Grb2/SOS1	0.024	0.03	-10000	0	-10000	0	0
STAT5A	0.011	0.017	0.14	1	-10000	0	1
GRB2	0.025	0.004	-10000	0	-10000	0	0
STAT5 (dimer)	0.022	0.026	0.16	1	-10000	0	1
LYN/PLCgamma2	0.037	0.009	-10000	0	-10000	0	0
PTPN11	0.025	0.004	-10000	0	-10000	0	0
BTK	0.02	0.092	0.16	39	-10000	0	39
BCL2	0.04	0.052	0.23	3	-10000	0	3

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.016	0.005	0	14	-10000	0	14
ADCY5	-0.014	0.007	0	27	-10000	0	27
ADCY6	-0.016	0.004	0	8	-10000	0	8
ADCY7	-0.017	0.003	0	6	-10000	0	6
ADCY1	-0.009	0.009	0	71	-10000	0	71
ADCY2	-0.016	0.005	0	11	-10000	0	11
ADCY3	-0.017	0.003	0	5	-10000	0	5
ADCY8	-0.016	0.005	0	12	-10000	0	12
PRKCE	-0.011	0.002	0	3	-10000	0	3
ADCY9	-0.017	0.003	0	6	-10000	0	6
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	0.005	0.049	0.15	7	-0.13	2	9

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.01	0.015	0.15	1	-10000	0	1
IHH	0.03	0.013	0.095	5	-10000	0	5
SHH Np/Cholesterol/GAS1	-0.016	0.013	0	54	-0.04	16	70
LRPAP1	0.026	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.016	0.013	0.04	16	0	54	70
SMO/beta Arrestin2	0.055	0.053	-10000	0	-10000	0	0
SMO	0.008	0.011	-10000	0	-10000	0	0
AKT1	0.002	0.071	-10000	0	-0.34	4	4
ARRB2	0.026	0.004	-10000	0	-10000	0	0
BOC	0.024	0.01	-10000	0	-0.058	2	2
ADRBK1	0.026	0.002	-10000	0	-10000	0	0
heart looping	0.009	0.012	-10000	0	-10000	0	0
STIL	0.024	0.08	0.16	35	-10000	0	35
DHH N/PTCH2	0.037	0.01	-10000	0	0	9	9
DHH N/PTCH1	0.031	0.011	-10000	0	-10000	0	0
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
DHH	0.023	0.013	-10000	0	-0.058	3	3
PTHLH	0.01	0.013	0.15	1	-10000	0	1
determination of left/right symmetry	0.009	0.012	-10000	0	-10000	0	0
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
skeletal system development	0.01	0.013	0.15	1	-10000	0	1
IHH N/Hhip	0.034	0.016	0.085	3	-10000	0	3
DHH N/Hhip	0.033	0.015	-10000	0	0	24	24
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	0.009	0.012	-10000	0	-10000	0	0
pancreas development	0.022	0.011	-10000	0	-0.058	1	1
HHAT	0.025	0.005	-10000	0	-10000	0	0
PI3K	0.036	0.01	-10000	0	0	10	10
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	0.009	0.033	-10000	0	-0.058	29	29
somite specification	0.009	0.012	-10000	0	-10000	0	0
SHH Np/Cholesterol/PTCH1	-0.012	0.009	-10000	0	-10000	0	0
SHH Np/Cholesterol/PTCH2	-0.014	0.011	0	57	-10000	0	57
SHH Np/Cholesterol/Megalin	-0.014	0.012	0	61	-0.04	2	63
SHH	-0.014	0.011	0	57	-0.047	2	59
catabolic process	0.016	0.005	-10000	0	-10000	0	0
SMO/Vitamin D3	-0.005	0.031	0.17	4	-10000	0	4
SHH Np/Cholesterol/Hhip	-0.013	0.012	0	67	-0.04	2	69
LRP2	0.023	0.008	-10000	0	-10000	0	0
receptor-mediated endocytosis	-0.009	0.025	0.15	3	-10000	0	3
SHH Np/Cholesterol/BOC	-0.014	0.011	0	56	-0.04	2	58
SHH Np/Cholesterol/CDO	-0.014	0.011	0	56	-0.04	2	58
mesenchymal cell differentiation	0.013	0.012	0.04	2	0	67	69
mol:Vitamin D3	0.039	0.09	0.18	41	-10000	0	41
IHH N/PTCH2	0.038	0.011	0.085	3	-10000	0	3
CDON	0.025	0.007	-10000	0	-0.058	1	1
IHH N/PTCH1	0.026	0.006	-10000	0	-10000	0	0
Megalin/LRPAP1	0.035	0.012	-10000	0	0	15	15
PTCH2	0.025	0.005	-10000	0	-10000	0	0
SHH Np/Cholesterol	-0.008	0.011	0.026	7	-10000	0	7
PTCH1	0.016	0.005	-10000	0	-10000	0	0
HHIP	0.022	0.011	-10000	0	-0.058	1	1

×

a4b1 and a4b7 Integrin signaling

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
ITGB1	0.017	0.015	-10000	0	-0.058	2	2
ITGB7	0.026	0.004	-10000	0	-10000	0	0
ITGA4	0.013	0.031	-10000	0	-0.058	23	23
alpha4/beta7 Integrin	0.041	0.01	-10000	0	0	3	3
alpha4/beta1 Integrin	0.031	0.021	0.082	2	0	43	45

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.025	0.004	-10000	0	-10000	0	0
HDAC3	0.026	0.003	-10000	0	-10000	0	0
VDR	0.023	0.015	-10000	0	-0.058	4	4
Cbp/p300/PCAF	0.047	0.017	-10000	0	-10000	0	0
EP300	0.024	0.007	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	-0.048	0.058	-10000	0	-0.2	13	13
KAT2B	0.026	0.002	-10000	0	-10000	0	0
MAPK14	0.026	0.004	-10000	0	-10000	0	0
AKT1	-0.065	0.054	-10000	0	-0.2	9	9
RAR alpha/9cRA/Cyclin H	-0.13	0.083	-10000	0	-0.25	37	37
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	-0.049	0.049	-10000	0	-0.18	11	11
CDC2	0	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.049	0.045	-10000	0	-0.24	1	1
NCOR2	0.025	0.004	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.019	0.005	0.041	4	0	7	11
RXRs/RARs/NRIP1/9cRA	-0.22	0.1	-10000	0	-0.34	33	33
NCOA2	0.025	0.004	-10000	0	-10000	0	0
NCOA3	0.024	0.007	-10000	0	-10000	0	0
NCOA1	0.026	0.003	-10000	0	-10000	0	0
VDR/VDR/DNA	0.023	0.015	-10000	0	-0.058	4	4
RARG	0.025	0.008	-10000	0	-0.058	1	1
RAR gamma1/9cRA	0.033	0.009	-10000	0	0	9	9
MAPK3	0.026	0.003	-10000	0	-10000	0	0
MAPK1	0.025	0.006	-10000	0	-10000	0	0
MAPK8	0.019	0.012	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.22	0.096	-10000	0	-0.26	120	120
RARA	0.001	0.003	-10000	0	-10000	0	0
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.049	0.05	-10000	0	-0.18	12	12
PRKCA	0.026	0.002	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.21	0.093	-10000	0	-0.32	32	32
RXRG	0.002	0.005	-10000	0	-10000	0	0
RXRA	-0.05	0.042	-10000	0	-10000	0	0
RXRB	0.002	0.004	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.019	0.005	0.041	4	0	7	11
RBP1	0.015	0.028	-10000	0	-0.058	18	18
CRBP1/9-cic-RA	0.022	0.007	0.041	18	0	2	20
RARB	0.026	0.002	-10000	0	-10000	0	0
PRKCG	0.003	0.008	-10000	0	-10000	0	0
MNAT1	0.025	0.006	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.22	0.13	-10000	0	-0.29	112	112
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.19	0.089	-10000	0	-0.27	48	48
proteasomal ubiquitin-dependent protein catabolic process	-0.092	0.067	-10000	0	-0.2	30	30
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.21	0.091	-10000	0	-0.31	33	33
positive regulation of DNA binding	-0.13	0.078	-10000	0	-0.24	37	37
NRIP1	-0.19	0.088	-10000	0	-0.4	1	1
RXRs/RARs	-0.2	0.093	-10000	0	-0.31	35	35
RXRs/RXRs/DNA/9cRA	-0.22	0.092	-10000	0	-0.26	122	122
PRKACA	0.025	0.006	-10000	0	-10000	0	0
CDK7	0.025	0.005	-10000	0	-10000	0	0
TFIIH	0.048	0.016	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.1	0.069	-10000	0	-0.19	33	33
CCNH	0.026	0.004	-10000	0	-10000	0	0
CREBBP	0.026	0.004	-10000	0	-10000	0	0
RAR gamma2/9cRA	0.041	0.028	-10000	0	-0.049	1	1

×

IL2 signaling events mediated by STAT5

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
GAB2	0.026	0.002	-10000	0	-10000	0	0
ELF1	0.032	0.01	-10000	0	-10000	0	0
CCNA2	-0.036	0.037	-10000	0	-0.058	108	108
PIK3CA	0.026	0.004	-10000	0	-10000	0	0
JAK3	0.025	0.005	-10000	0	-10000	0	0
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
JAK1	0.025	0.005	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.005	0.044	-10000	0	-0.26	1	1
SHC1	0.024	0.013	-10000	0	-0.058	3	3
SP1	0.028	0.004	-10000	0	-10000	0	0
IL2RA	-0.024	0.018	0	46	-0.042	67	113
IL2RB	0.019	0.021	-10000	0	-0.058	9	9
SOS1	0.026	0	-10000	0	-10000	0	0
IL2RG	0.02	0.022	-10000	0	-0.058	11	11
G1/S transition of mitotic cell cycle	0.052	0.08	0.32	5	-0.22	1	6
PTPN11	0.026	0.004	-10000	0	-10000	0	0
CCND2	-0.018	0.005	-10000	0	-10000	0	0
LCK	0.003	0.037	-10000	0	-0.058	40	40
GRB2	0.026	0.004	-10000	0	-10000	0	0
IL2	0.02	0.002	-10000	0	-10000	0	0
CDK6	0.013	0.019	-10000	0	-0.058	6	6
CCND3	0.001	0.046	-10000	0	-10000	0	0

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0.015	0.023	-9999	0	-0.018	6	6
MAPK9	0.004	0.001	-9999	0	-10000	0	0
adrenocorticotropin secretion	-0.007	0.005	0	59	-10000	0	59
GNB1/GNG2	0.031	0.011	-9999	0	0	17	17
GNB1	0.025	0.006	-9999	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-9999	0	-10000	0	0
mol:GDP	0	0	-9999	0	-10000	0	0
MAPK14	0.004	0.001	-9999	0	-10000	0	0
Gs family/GTP	0.006	0.008	-9999	0	0	91	91
EntrezGene:2778	0	0	-9999	0	-10000	0	0
vasopressin secretion	0	0	-9999	0	-10000	0	0
G-protein coupled receptor activity	0	0	-9999	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-9999	0	-10000	0	0
glutamate secretion	0.001	0.001	-9999	0	0	89	89
GNAL	0.01	0.013	-9999	0	-10000	0	0
GNG2	0.025	0.006	-9999	0	-10000	0	0
CRH	0.014	0.012	-9999	0	-10000	0	0
mol:cortisol	0	0	-9999	0	-10000	0	0
MAPK8	0.003	0.002	-9999	0	-10000	0	0
MAPK11	0.004	0.001	-9999	0	-10000	0	0

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.025	0.006	-10000	0	-10000	0	0
CCL5	0.015	0.028	-10000	0	-0.058	19	19
SDCBP	0.025	0.004	-10000	0	-10000	0	0
FGFR/FGF2/Syndecan-1	0.002	0.036	-10000	0	-0.22	1	1
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	0.01	0.03	0.17	1	-0.21	1	2
Syndecan-1/Syntenin	0.025	0.049	0.22	5	-10000	0	5
MAPK3	-0.015	0.035	0.1	4	-0.21	1	5
HGF/MET	0.023	0.019	-10000	0	0	60	60
TGFB1/TGF beta receptor Type II	0.025	0.006	-10000	0	-10000	0	0
BSG	0.025	0.006	-10000	0	-10000	0	0
keratinocyte migration	0.01	0.029	0.17	1	-0.21	1	2
Syndecan-1/RANTES	0.026	0.053	0.22	5	-0.21	1	6
Syndecan-1/CD147	0.033	0.037	-10000	0	-0.21	1	1
Syndecan-1/Syntenin/PIP2	0.024	0.046	0.2	5	-10000	0	5
LAMA5	0.023	0.008	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	0.023	0.045	0.2	5	-10000	0	5
MMP7	-0.032	0.039	-10000	0	-0.058	101	101
HGF	0.018	0.012	-10000	0	-10000	0	0
Syndecan-1/CASK	0.001	0.032	-10000	0	-0.21	1	1
Syndecan-1/HGF/MET	0.022	0.035	0.25	1	-10000	0	1
regulation of cell adhesion	-0.008	0.074	0.27	7	-0.21	1	8
HPSE	0.014	0.029	-10000	0	-0.058	20	20
positive regulation of cell migration	0.002	0.036	-10000	0	-0.22	1	1
SDC1	0.002	0.036	0.11	9	-0.16	2	11
Syndecan-1/Collagen	0.002	0.036	-10000	0	-0.22	1	1
PPIB	0.026	0.004	-10000	0	-10000	0	0
MET	0.016	0.013	-10000	0	-10000	0	0
PRKACA	0.025	0.006	-10000	0	-10000	0	0
MMP9	-0.043	0.031	-10000	0	-0.058	116	116
MAPK1	-0.014	0.036	0.1	4	-0.21	1	5
homophilic cell adhesion	0.005	0.044	0.22	2	-0.22	1	3
MMP1	-0.01	0.041	-10000	0	-0.058	62	62

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.053	0.033	-10000	0	-0.028	15	15
MAP4K1	0.025	0.006	-10000	0	-10000	0	0
MAP3K8	0.018	0.013	-10000	0	-0.058	1	1
PRKCB	0.012	0.013	-10000	0	-10000	0	0
DBNL	0.018	0.012	-10000	0	-10000	0	0
CRKL	0.025	0.006	-10000	0	-10000	0	0
MAP3K1	0.019	0.034	-10000	0	-10000	0	0
JUN	-0.31	0.27	-10000	0	-0.51	92	92
MAP3K7	0.014	0.036	-10000	0	-0.18	1	1
GRAP2	0.022	0.012	-10000	0	-0.058	2	2
CRK	0.026	0.004	-10000	0	-10000	0	0
MAP2K4	-0.001	0.047	0.16	3	-10000	0	3
LAT	0.026	0.004	-10000	0	-10000	0	0
LCP2	0.025	0.008	-10000	0	-0.058	1	1
MAPK8	-0.33	0.28	-10000	0	-0.53	94	94
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.028	0.044	-10000	0	-0.19	2	2
LAT/GRAP2/SLP76/HPK1/HIP-55	0.046	0.041	-10000	0	-10000	0	0

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0	0.012	-10000	0	-0.095	1	1
BUB1B	-0.006	0.03	0.078	1	-0.14	3	4
PLK1	0.001	0.025	0.06	14	-0.1	1	15
PLK1S1	0.009	0.023	0.094	2	-10000	0	2
KIF2A	-0.005	0.031	0.26	1	-0.099	1	2
regulation of mitotic centrosome separation	0.001	0.025	0.061	13	-0.1	1	14
GOLGA2	0.025	0.006	-10000	0	-10000	0	0
Hec1/SPC24	0.05	0.044	0.11	13	-0.088	7	20
WEE1	0.008	0.069	-10000	0	-0.34	5	5
cytokinesis	0	0.029	-10000	0	-0.15	3	3
PP2A-alpha B56	0.065	0.052	-10000	0	-0.51	1	1
AURKA	0.008	0.018	-10000	0	-10000	0	0
PICH/PLK1	-0.027	0.05	0.15	10	-0.093	4	14
CENPE	-0.01	0.023	-10000	0	-0.12	1	1
RhoA/GTP	0.019	0.002	-10000	0	0	1	1
positive regulation of microtubule depolymerization	-0.005	0.03	0.26	1	-0.099	1	2
PPP2CA	0.026	0.003	-10000	0	-10000	0	0
FZR1	0.025	0.006	-10000	0	-10000	0	0
TPX2	0.012	0.025	0.094	7	-10000	0	7
PAK1	0.025	0.004	-10000	0	-10000	0	0
SPC24	-0.016	0.041	-10000	0	-0.058	71	71
FBXW11	0.026	0.003	-10000	0	-10000	0	0
CLSPN	0.006	0.025	-10000	0	-0.22	1	1
GORASP1	0.026	0.002	-10000	0	-10000	0	0
metaphase	0	0.001	0.013	1	-0.011	1	2
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	-0.001	0.014	0.033	13	-0.053	1	14
G2 phase of mitotic cell cycle	-0.001	0.003	0.009	4	-10000	0	4
STAG2	0.026	0.003	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.015	0.009	-10000	0	-10000	0	0
spindle elongation	0.001	0.025	0.061	13	-0.1	1	14
ODF2	0.025	0.006	-10000	0	-10000	0	0
BUB1	0.042	0.05	-10000	0	-0.54	1	1
TPT1	-0.004	0.045	-10000	0	-0.19	7	7
CDC25C	0.012	0.033	-10000	0	-0.25	2	2
CDC25B	0.024	0.009	-10000	0	-0.023	2	2
SGOL1	0	0.012	0.096	1	-10000	0	1
RHOA	0.026	0.002	-10000	0	-10000	0	0
CCNB1/CDK1	0.038	0.036	-10000	0	-0.11	6	6
CDC14B	-0.011	0.003	0.008	2	-10000	0	2
CDC20	-0.052	0.022	-10000	0	-0.058	134	134
PLK1/PBIP1	-0.018	0.021	0.043	3	-0.072	4	7
mitosis	-0.004	0.003	-10000	0	-10000	0	0
FBXO5	-0.007	0.039	0.11	4	-0.1	12	16
CDC2	-0.001	0.002	-10000	0	-0.011	1	1
NDC80	-0.055	0.013	-10000	0	-0.058	140	140
metaphase plate congression	0.007	0.022	-10000	0	-0.2	1	1
ERCC6L	-0.017	0.045	0.12	10	-0.12	6	16
NLP/gamma Tubulin	0	0.014	0.051	1	-0.059	1	2
microtubule cytoskeleton organization	-0.004	0.044	-10000	0	-0.19	7	7
G2/M transition DNA damage checkpoint	-0.001	0.002	-10000	0	-10000	0	0
PPP1R12A	0.025	0.006	-10000	0	-10000	0	0
interphase	-0.001	0.002	-10000	0	-10000	0	0
PLK1/PRC1-2	0.046	0.037	0.1	8	-0.079	6	14
GRASP65/GM130/RAB1/GTP/PLK1	0.04	0.03	-10000	0	-0.097	1	1
RAB1A	0.026	0.003	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.001	0.024	0.063	15	-0.072	1	16
mitotic prometaphase	-0.001	0.002	0.02	1	-10000	0	1
proteasomal ubiquitin-dependent protein catabolic process	-0.042	0.09	-10000	0	-0.2	37	37
microtubule-based process	0.034	0.033	0.087	14	-0.076	6	20
Golgi organization	0.001	0.025	0.061	13	-0.1	1	14
Cohesin/SA2	0.013	0.024	0.072	2	-0.091	1	3
PPP1CB/MYPT1	0.037	0.009	-10000	0	0	8	8
KIF20A	-0.056	0.012	-10000	0	-0.058	143	143
APC/C/CDC20	0.033	0.033	0.088	13	-0.075	7	20
PPP2R1A	0.025	0.006	-10000	0	-10000	0	0
chromosome segregation	-0.018	0.021	0.043	3	-0.071	4	7
PRC1	0.025	0.008	-10000	0	-0.058	1	1
ECT2	-0.005	0.028	0.2	1	-0.099	1	2
C13orf34	0.001	0.022	0.055	14	-0.083	1	15
NUDC	0.006	0.022	-10000	0	-0.2	1	1
regulation of attachment of spindle microtubules to kinetochore	-0.006	0.03	0.078	1	-0.14	3	4
spindle assembly	-0.001	0.02	0.056	5	-0.085	1	6
spindle stabilization	0.009	0.023	0.094	2	-10000	0	2
APC/C/HCDH1	0.019	0.006	-10000	0	-10000	0	0
MKLP2/PLK1	0.034	0.033	0.087	14	-0.077	6	20
CCNB1	0.018	0.026	0.057	2	-0.059	14	16
PPP1CB	0.026	0.003	-10000	0	-10000	0	0
BTRC	0.018	0.012	-10000	0	-10000	0	0
ROCK2	0.01	0.03	-10000	0	-0.29	1	1
TUBG1	0.005	0.014	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.015	0.021	-10000	0	-0.11	5	5
MLF1IP	-0.032	0.011	-10000	0	-0.037	123	123
INCENP	0.026	0.002	-10000	0	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	0.013	0.03	-10000	0	-0.34	1	1
Crk/p130 Cas/Paxillin	-0.072	0.063	-10000	0	-0.16	43	43
JUN	-0.022	0.039	-10000	0	-0.18	4	4
HRAS	0.025	0.006	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	0.028	0.035	-10000	0	-0.026	10	10
RAP1A	0.026	0.004	-10000	0	-10000	0	0
FRS2	0.024	0.007	-10000	0	-10000	0	0
RAP1A/GDP	0.019	0.003	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	0.031	0.04	-10000	0	-0.026	31	31
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.025	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.026	0.004	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	0.023	0.031	-10000	0	-0.021	35	35
RHOA	0.026	0.002	-10000	0	-10000	0	0
RAP1A/GTP	0.026	0.041	-10000	0	-10000	0	0
GRB7	0.023	0.01	-10000	0	-0.058	2	2
RET51/GFRalpha1/GDNF	0.031	0.039	-10000	0	-0.026	11	11
MAPKKK cascade	-0.06	0.04	-10000	0	-0.13	32	32
BCAR1	0.025	0.005	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	0.024	0.03	-10000	0	-0.021	33	33
lamellipodium assembly	-0.026	0.061	-10000	0	-0.15	21	21
RET51/GFRalpha1/GDNF/SHC	0.03	0.04	-10000	0	-0.026	31	31
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	0.023	0.031	-10000	0	-0.021	32	32
RET9/GFRalpha1/GDNF/Shank3	0.023	0.03	-10000	0	-0.02	34	34
MAPK3	-0.017	0.054	0.19	6	-10000	0	6
DOK1	0.026	0	-10000	0	-10000	0	0
DOK6	0.013	0.013	-10000	0	-10000	0	0
PXN	0.026	0.003	-10000	0	-10000	0	0
neurite development	-0.018	0.037	0.14	5	-10000	0	5
DOK5	0.024	0.007	-10000	0	-10000	0	0
GFRA1	0.015	0.013	-10000	0	-10000	0	0
MAPK8	-0.02	0.041	-10000	0	-0.18	5	5
HRAS/GTP	-0.009	0.08	-10000	0	-0.13	34	34
tube development	0.018	0.032	0.21	1	-10000	0	1
MAPK1	-0.015	0.055	0.19	7	-10000	0	7
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.019	0.05	-10000	0	-0.1	27	27
Rac1/GDP	0.013	0.009	-10000	0	-10000	0	0
SRC	0.024	0.007	-10000	0	-10000	0	0
PDLIM7	0.025	0.01	-10000	0	-0.058	2	2
RET51/GFRalpha1/GDNF/Dok6	0.02	0.043	-10000	0	-10000	0	0
SHC1	0.023	0.013	-10000	0	-0.058	3	3
RET51/GFRalpha1/GDNF/Dok4	0.031	0.04	-10000	0	-0.026	29	29
RET51/GFRalpha1/GDNF/Dok5	0.032	0.039	-10000	0	-0.026	10	10
PRKCA	0.026	0.002	-10000	0	-10000	0	0
HRAS/GDP	0.018	0.004	-10000	0	-10000	0	0
CREB1	-0.046	0.091	-10000	0	-0.2	32	32
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.023	0.052	-10000	0	-0.1	31	31
RET51/GFRalpha1/GDNF/Grb7	0.03	0.04	-10000	0	-0.026	31	31
mol:GDP	0	0	-10000	0	-10000	0	0
RET	0.017	0.012	-10000	0	-10000	0	0
DOK4	0.025	0.004	-10000	0	-10000	0	0
JNK cascade	-0.021	0.039	-10000	0	-0.18	4	4
RET9/GFRalpha1/GDNF/FRS2	0.023	0.03	-10000	0	-0.02	30	30
SHANK3	0.023	0.009	-10000	0	-10000	0	0
RASA1	0.026	0.004	-10000	0	-10000	0	0
NCK1	0.026	0.004	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.013	0.045	-10000	0	-0.097	32	32
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.038	0.085	-10000	0	-0.2	28	28
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.045	0.089	-10000	0	-0.2	33	33
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.001	0.034	-10000	0	-10000	0	0
PI3K	-0.073	0.096	-10000	0	-0.21	43	43
SOS1	0.026	0	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	0.027	0.039	-10000	0	-0.026	24	24
GRB10	0.017	0.013	-10000	0	-10000	0	0
activation of MAPKK activity	0.009	0.016	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/FRS2	0.03	0.039	-10000	0	-0.026	27	27
GAB1	0.026	0.004	-10000	0	-10000	0	0
IRS1	0.026	0	-10000	0	-10000	0	0
IRS2	0.025	0.006	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.001	0.034	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/PKC alpha	0.031	0.04	-10000	0	-0.026	31	31
GRB2	0.025	0.004	-10000	0	-10000	0	0
PRKACA	0.025	0.006	-10000	0	-10000	0	0
GDNF	0.023	0.004	-10000	0	-10000	0	0
RAC1	0.017	0.012	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	0.031	0.04	-10000	0	-0.026	31	31
Rac1/GTP	-0.029	0.071	-10000	0	-0.18	21	21
RET9/GFRalpha1/GDNF	0.019	0.017	-10000	0	0	63	63
GFRalpha1/GDNF	0.021	0.019	-10000	0	0	63	63

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.024	0.007	-10000	0	-10000	0	0
NFATC1	-0.011	0.079	-10000	0	-0.29	4	4
NFATC2	-0.059	0.088	-10000	0	-0.2	31	31
NFATC3	0.007	0.016	-10000	0	-0.052	9	9
YWHAE	0.026	0.004	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.16	0.1	-10000	0	-0.23	92	92
Exportin 1/Ran/NUP214	0.049	0.014	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.15	0.1	-10000	0	-0.22	88	88
BCL2/BAX	0.035	0.011	-10000	0	0	14	14
CaM/Ca2+/Calcineurin A alpha-beta B1	0.018	0.005	-10000	0	0	11	11
CaM/Ca2+	0.018	0.005	-10000	0	0	11	11
BAX	0.025	0.006	-10000	0	-10000	0	0
MAPK14	0.026	0.004	-10000	0	-10000	0	0
BAD	0.026	0.002	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.16	0.11	-10000	0	-0.23	90	90
Calcineurin A alpha-beta B1/BCL2	0.025	0.005	-10000	0	-10000	0	0
FKBP8	0.025	0.006	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.16	0.1	0.22	90	-10000	0	90
KPNB1	0.026	0	-10000	0	-10000	0	0
KPNA2	0.026	0.002	-10000	0	-10000	0	0
XPO1	0.026	0	-10000	0	-10000	0	0
SFN	0.024	0.013	-10000	0	-0.058	3	3
MAP3K8	0.018	0.013	-10000	0	-0.058	1	1
NFAT4/CK1 alpha	0.001	0.036	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.032	0.1	-10000	0	-0.19	27	27
CABIN1	-0.16	0.11	-10000	0	-0.23	89	89
CALM1	0.024	0.007	-10000	0	-10000	0	0
RAN	0.026	0.004	-10000	0	-10000	0	0
MAP3K1	0.026	0.004	-10000	0	0	3	3
CAMK4	0.021	0.01	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
MAPK3	0.026	0.003	-10000	0	-10000	0	0
YWHAH	0.024	0.007	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.026	0.018	-10000	0	0	50	50
YWHAB	0.024	0.007	-10000	0	-10000	0	0
MAPK8	0.018	0.012	-10000	0	-10000	0	0
MAPK9	0.026	0.003	-10000	0	-10000	0	0
YWHAG	0.018	0.012	-10000	0	-10000	0	0
FKBP1A	0.024	0.007	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	-0.035	0.11	-10000	0	-0.28	10	10
PRKCH	0.024	0.007	-10000	0	-10000	0	0
CABIN1/Cbp/p300	0.035	0.012	-10000	0	-10000	0	0
CASP3	0.024	0.009	-10000	0	-0.058	1	1
PIM1	0.026	0.004	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.016	0.005	-10000	0	0	12	12
apoptosis	0.014	0.014	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.004	0.032	-10000	0	-0.18	2	2
PRKCB	0.012	0.013	-10000	0	-10000	0	0
PRKCE	0.026	0.004	-10000	0	-10000	0	0
JNK2/NFAT4	-0.02	0.077	-10000	0	-0.15	36	36
BAD/BCL-XL	0.035	0.011	-10000	0	0	14	14
PRKCD	0.026	0.002	-10000	0	-10000	0	0
NUP214	0.025	0.006	-10000	0	-10000	0	0
PRKCZ	0.019	0.011	-10000	0	-10000	0	0
PRKCA	0.026	0.002	-10000	0	-10000	0	0
PRKCG	0.003	0.008	-10000	0	-10000	0	0
PRKCQ	0.018	0.012	-10000	0	-10000	0	0
FKBP38/BCL2	0.035	0.011	-10000	0	0	13	13
EP300	0.024	0.007	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.024	0.007	-10000	0	-10000	0	0
NFATc/JNK1	-0.007	0.071	-10000	0	-0.28	4	4
CaM/Ca2+/FKBP38	0.031	0.011	-10000	0	0	17	17
FKBP12/FK506	0.018	0.005	-10000	0	0	12	12
CSNK1A1	-0.016	0.005	0	13	-10000	0	13
CaM/Ca2+/CAMK IV	0.027	0.015	-10000	0	0	35	35
NFATc/ERK1	-0.002	0.083	-10000	0	-0.28	4	4
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.15	0.1	-10000	0	-0.22	91	91
NR4A1	-0.06	0.073	0.14	3	-0.2	19	22
GSK3B	0.026	0.004	-10000	0	-10000	0	0
positive T cell selection	0.007	0.016	-10000	0	-0.052	9	9
NFAT1/CK1 alpha	-0.038	0.064	-10000	0	-0.14	32	32
RCH1/ KPNB1	0.039	0.003	-10000	0	0	1	1
YWHAQ	0.026	0.002	-10000	0	-10000	0	0
PRKACA	0.025	0.006	-10000	0	-10000	0	0
AKAP5	0.018	0.012	-10000	0	-10000	0	0
MEF2D	0.025	0.004	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.025	0.005	-10000	0	-10000	0	0
NFATc/p38 alpha	-0.002	0.083	-10000	0	-0.28	4	4
CREBBP	0.026	0.004	-10000	0	-10000	0	0
BCL2	0.025	0.005	-10000	0	-10000	0	0

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	0.029	0.013	-9999	0	25	25
EFNA5	0.024	0.007	-9999	-9999	0	0
FYN	-0.017	0.01	-9999	-9999	0	0
neuron projection morphogenesis	0.029	0.013	-9999	0	25	25
cell-cell signaling	0	0	-9999	-9999	0	0
Ephrin A5/EPHA5	0.029	0.013	-9999	0	25	25
EPHA5	0.023	0.008	-9999	-9999	0	0

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.022	0.009	-10000	0	-10000	0	0
HRAS	0.025	0.006	-10000	0	-10000	0	0
EGFR	0.007	0.016	-10000	0	-0.058	4	4
AKT	0.13	0.11	0.23	65	-10000	0	65
FOXO3	0.024	0.008	-10000	0	-10000	0	0
AKT1	0.024	0.007	-10000	0	-10000	0	0
FOXO1	0.025	0.006	-10000	0	-10000	0	0
AKT3	0.025	0.006	-10000	0	-10000	0	0
FOXO4	0.026	0.002	-10000	0	-10000	0	0
MET	0.016	0.013	-10000	0	-10000	0	0
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
PIK3CB	0.026	0.004	-10000	0	-10000	0	0
NRAS	0.026	0.003	-10000	0	-10000	0	0
PIK3CG	0.018	0.012	-10000	0	-10000	0	0
PIK3R3	0.025	0.004	-10000	0	-10000	0	0
PIK3R2	0.025	0.006	-10000	0	-10000	0	0
NF1	0.026	0.004	-10000	0	-10000	0	0
RAS	0.033	0.046	0.096	41	-0.073	2	43
ERBB2	0.026	0	-10000	0	-10000	0	0
proliferation/survival/translation	-0.045	0.066	0.19	3	-0.2	8	11
PI3K	0.1	0.12	0.2	69	-0.098	2	71
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
KRAS	0.025	0.006	-10000	0	-10000	0	0
FOXO	0.13	0.098	0.2	73	-10000	0	73
AKT2	0.025	0.006	-10000	0	-10000	0	0
PTEN	0.016	0.013	-10000	0	-10000	0	0

×

LPA receptor mediated 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
GNB1/GNG2	0.043	0.026	-10000	0	-0.024	15	15
NF kappa B1 p50/RelA/I kappa B alpha	-0.01	0.083	0.23	7	-0.23	3	10
AP1	0.026	0.03	-10000	0	-0.056	1	1
mol:PIP3	-0.015	0.021	-10000	0	-10000	0	0
AKT1	0.013	0.07	0.21	8	-10000	0	8
PTK2B	0.007	0.047	0.17	7	-0.16	2	9
RHOA	0.026	0.053	0.18	7	-10000	0	7
PIK3CB	0.025	0.006	-10000	0	-0.033	1	1
mol:Ca2+	-0.016	0.038	0.16	4	-10000	0	4
MAGI3	0.026	0.003	-10000	0	-10000	0	0
RELA	0.026	0.003	-10000	0	-10000	0	0
apoptosis	-0.01	0.026	-10000	0	-0.065	20	20
HRAS/GDP	0.018	0.004	-10000	0	0	8	8
positive regulation of microtubule depolymerization	-0.004	0.043	0.17	3	-0.17	1	4
NF kappa B1 p50/RelA	-0.038	0.031	0.13	1	-10000	0	1
endothelial cell migration	-0.025	0.016	-10000	0	-0.047	49	49
ADCY4	0.017	0.046	0.12	3	-0.12	4	7
ADCY5	0.011	0.049	0.12	3	-0.11	4	7
ADCY6	0.019	0.042	0.12	3	-0.11	1	4
ADCY7	0.019	0.042	0.12	2	-0.11	1	3
ADCY1	-0.013	0.042	0.12	3	-0.12	4	7
ADCY2	0.018	0.045	0.12	3	-0.12	2	5
ADCY3	0.019	0.044	0.12	3	-0.11	2	5
ADCY8	0.019	0.04	0.12	2	-10000	0	2
ADCY9	0.02	0.041	0.12	3	-10000	0	3
GSK3B	0.002	0.046	0.16	7	-0.18	1	8
arachidonic acid secretion	0.01	0.039	0.076	18	-10000	0	18
GNG2	0.024	0.008	-10000	0	-0.033	1	1
TRIP6	0.009	0.007	-10000	0	-10000	0	0
GNAO1	-0.019	0.01	-10000	0	-0.04	3	3
HRAS	0.025	0.006	-10000	0	-10000	0	0
NFKBIA	-0.019	0.08	0.23	7	-0.24	3	10
GAB1	0.026	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	0.01	0.13	-10000	0	-0.73	4	4
JUN	0.025	0.004	-10000	0	-10000	0	0
LPA/LPA2/NHERF2	0.033	0.01	-10000	0	-0.03	1	1
TIAM1	0.009	0.15	-10000	0	-0.87	4	4
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
mol:IP3	-0.015	0.028	0.14	3	-10000	0	3
PLCB3	-0.014	0.042	0.17	7	-10000	0	7
FOS	0.024	0.008	-10000	0	-10000	0	0
positive regulation of mitosis	0.01	0.039	0.076	18	-10000	0	18
LPA/LPA1-2-3	0.039	0.026	-10000	0	-0.028	6	6
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0	-10000	0	-10000	0	0
BCAR1	0.025	0.005	-10000	0	-10000	0	0
stress fiber formation	0.013	0.049	0.18	7	-10000	0	7
GNAZ	-0.02	0.01	-10000	0	-0.04	3	3
EGFR/PI3K-beta/Gab1	-0.015	0.022	-10000	0	-10000	0	0
positive regulation of dendritic cell cytokine production	0.038	0.025	-10000	0	-0.028	6	6
LPA/LPA2/MAGI-3	0.034	0.009	-10000	0	-10000	0	0
ARHGEF1	0.034	0.096	0.18	44	-10000	0	44
GNAI2	-0.021	0.009	-10000	0	-0.051	1	1
GNAI3	-0.02	0.009	-10000	0	-0.043	2	2
GNAI1	-0.013	0.012	-10000	0	-10000	0	0
LPA/LPA3	0.009	0.015	-10000	0	-0.019	28	28
LPA/LPA2	0.017	0.009	-10000	0	-0.023	6	6
LPA/LPA1	0.004	0.025	-10000	0	-0.03	49	49
HB-EGF/EGFR	-0.015	0.021	-10000	0	-0.065	2	2
HBEGF	-0.038	0.016	-10000	0	-0.046	112	112
mol:DAG	-0.015	0.028	0.14	3	-10000	0	3
cAMP biosynthetic process	0.019	0.056	0.14	9	-10000	0	9
NFKB1	0.026	0.002	-10000	0	-10000	0	0
SRC	0.024	0.007	-10000	0	-10000	0	0
GNB1	0.025	0.006	-10000	0	-10000	0	0
LYN	-0.009	0.071	0.23	7	-10000	0	7
GNAQ	-0.01	0.022	-10000	0	-0.061	18	18
LPAR2	0.025	0.007	-10000	0	-0.027	1	1
LPAR3	0.02	0.009	-10000	0	-10000	0	0
LPAR1	0.006	0.027	-10000	0	-0.031	49	49
IL8	0.013	0.078	0.28	8	-0.32	1	9
PTK2	-0.015	0.05	0.17	10	-10000	0	10
Rac1/GDP	0.013	0.009	-10000	0	0	49	49
CASP3	-0.01	0.026	-10000	0	-0.066	20	20
EGFR	0.007	0.016	-10000	0	-0.058	4	4
PLCG1	-0.005	0.03	0.14	2	-0.088	2	4
PLD2	-0.014	0.052	0.17	11	-10000	0	11
G12/G13	0.035	0.027	-10000	0	-0.044	1	1
PI3K-beta	-0.012	0.034	0.087	1	-0.15	1	2
cell migration	0.009	0.043	0.17	1	-0.23	3	4
SLC9A3R2	0.026	0.004	-10000	0	-10000	0	0
PXN	0.013	0.049	0.18	7	-10000	0	7
HRAS/GTP	0.01	0.039	0.076	20	-10000	0	20
RAC1	0.017	0.012	-10000	0	-10000	0	0
MMP9	-0.043	0.031	-10000	0	-0.058	116	116
PRKCE	0.025	0.006	-10000	0	-0.033	1	1
PRKCD	-0.011	0.069	0.24	8	-10000	0	8
Gi(beta/gamma)	0.014	0.045	0.085	37	-0.11	2	39
mol:LPA	-0.004	0.007	-10000	0	-0.021	3	3
TRIP6/p130 Cas/FAK1/Paxillin	0.035	0.041	0.15	1	-10000	0	1
MAPKKK cascade	0.01	0.039	0.076	18	-10000	0	18
contractile ring contraction involved in cytokinesis	0.026	0.053	0.18	7	-10000	0	7
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.01	0.022	-10000	0	-0.061	18	18
GNA15	-0.01	0.022	-10000	0	-0.061	18	18
GNA12	0.017	0.012	-10000	0	-10000	0	0
GNA13	0.026	0.002	-10000	0	-10000	0	0
MAPT	-0.005	0.044	0.17	3	-0.18	1	4
GNA11	-0.01	0.022	-10000	0	-0.061	18	18
Rac1/GTP	0.01	0.13	-10000	0	-0.77	4	4
MMP2	-0.025	0.016	-10000	0	-0.047	49	49

×

EGFR-dependent Endothelin 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
HRAS	0.025	0.006	-9999	0	-10000	0	0
EGFR	0.007	0.016	-9999	0	-0.058	4	4
EGF/EGFR	0.017	0.027	-9999	0	-0.035	4	4
EGF/EGFR dimer/SHC/GRB2/SOS1	0.028	0.038	-9999	0	-10000	0	0
mol:GTP	0	0	-9999	0	-10000	0	0
EDNRA	0.023	0.014	-9999	0	-0.058	4	4
response to oxidative stress	0	0	-9999	0	-10000	0	0
EGF	0.026	0.002	-9999	0	0	1	1
EGF/EGFR dimer/SHC	0.02	0.027	-9999	0	-10000	0	0
mol:GDP	0.025	0.035	-9999	0	-10000	0	0
mol:Ca2+	0	0	-9999	0	-10000	0	0
EDN1	0.025	0.005	-9999	0	-10000	0	0
GRB2/SOS1	0.038	0.006	-9999	0	0	4	4
HRAS/GTP	0.015	0.026	-9999	0	-0.051	1	1
SHC1	0.023	0.013	-9999	0	-0.058	3	3
HRAS/GDP	0.021	0.035	-9999	0	-10000	0	0
FRAP1	-0.012	0.017	0	96	-10000	0	96
EGF/EGFR dimer	0.015	0.02	-9999	0	0	94	94
SOS1	0.026	0	-9999	0	-10000	0	0
GRB2	0.025	0.004	-9999	0	-10000	0	0
ETA receptor/Endothelin-1	0.037	0.01	-9999	0	0	9	9

×

Syndecan-4-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
PTK2	0.016	0.026	-10000	0	-0.21	1	1
Syndecan-4/Syndesmos	0.026	0.07	-10000	0	-0.32	1	1
positive regulation of JNK cascade	0.02	0.059	-10000	0	-0.3	1	1
Syndecan-4/ADAM12	0.019	0.052	-10000	0	-0.31	1	1
CCL5	0.015	0.028	-10000	0	-0.058	19	19
Rac1/GDP	0.013	0.009	-10000	0	-10000	0	0
DNM2	0.025	0.006	-10000	0	-10000	0	0
ITGA5	0.012	0.03	-10000	0	-0.058	22	22
SDCBP	0.025	0.004	-10000	0	-10000	0	0
PLG	0.014	0.019	-10000	0	-0.042	12	12
ADAM12	-0.007	0.034	-10000	0	-0.058	42	42
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0.026	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.045	0.021	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	0.025	0.071	-10000	0	-0.31	1	1
Syndecan-4/CXCL12/CXCR4	0.021	0.062	-10000	0	-0.31	1	1
Syndecan-4/Laminin alpha3	0.022	0.069	-10000	0	-0.31	1	1
MDK	-0.03	0.04	-10000	0	-0.058	96	96
Syndecan-4/FZD7	0.03	0.072	-10000	0	-0.32	1	1
Syndecan-4/Midkine	0.038	0.076	-10000	0	-0.31	1	1
FZD7	0.014	0.03	-10000	0	-0.058	21	21
Syndecan-4/FGFR1/FGF	0.04	0.073	-10000	0	-0.31	1	1
THBS1	0.021	0.02	-10000	0	-0.058	8	8
integrin-mediated signaling pathway	0.04	0.074	-10000	0	-0.32	1	1
positive regulation of MAPKKK cascade	0.02	0.059	-10000	0	-0.3	1	1
Syndecan-4/TACI	0.024	0.07	-10000	0	-0.32	1	1
CXCR4	0.012	0.031	-10000	0	-0.058	24	24
cell adhesion	-0.004	0.02	-10000	0	-0.075	3	3
Syndecan-4/Dynamin	0.022	0.067	-10000	0	-0.32	1	1
Syndecan-4/TSP1	0.025	0.069	-10000	0	-0.31	1	1
Syndecan-4/GIPC	0.022	0.067	-10000	0	-0.32	1	1
Syndecan-4/RANTES	0.029	0.072	-10000	0	-0.32	1	1
ITGB1	0.017	0.015	-10000	0	-0.058	2	2
LAMA1	0.024	0.011	-10000	0	-0.058	2	2
LAMA3	0.024	0.007	-10000	0	-10000	0	0
RAC1	0.017	0.012	-10000	0	-10000	0	0
PRKCA	-0.008	0.055	0.64	1	-10000	0	1
Syndecan-4/alpha-Actinin	0.024	0.066	-10000	0	-0.31	1	1
TFPI	-0.031	0.039	-10000	0	-0.058	100	100
F2	0.024	0.013	0.075	1	-10000	0	1
alpha5/beta1 Integrin	0.03	0.022	0.082	2	0	46	48
positive regulation of cell adhesion	0.01	0.066	-10000	0	-0.31	1	1
ACTN1	0.024	0.007	-10000	0	-10000	0	0
TNC	-0.043	0.032	-10000	0	-0.058	118	118
Syndecan-4/CXCL12	0.015	0.049	-10000	0	-0.31	1	1
FGF6	0.019	0.005	-10000	0	-10000	0	0
RHOA	0.026	0.002	-10000	0	-10000	0	0
CXCL12	0.018	0.012	-10000	0	-10000	0	0
TNFRSF13B	0.021	0.003	-10000	0	-10000	0	0
FGF2	0.026	0.002	-10000	0	-10000	0	0
FGFR1	0.025	0.004	-10000	0	-10000	0	0
Syndecan-4/PI-4-5-P2	-0.002	0.048	-10000	0	-0.31	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.006	0.037	-10000	0	-0.058	31	31
cell migration	-0.023	0.013	-10000	0	-10000	0	0
PRKCD	0.022	0.02	-10000	0	-0.09	1	1
vasculogenesis	0.025	0.068	-10000	0	-0.3	1	1
SDC4	-0.002	0.05	-10000	0	-0.32	1	1
Syndecan-4/Tenascin C	0.041	0.075	-10000	0	-0.33	1	1
Syndecan-4/PI-4-5-P2/PKC alpha	-0.036	0.017	-10000	0	-10000	0	0
Syndecan-4/Syntenin	0.026	0.071	-10000	0	-0.32	1	1
MMP9	-0.035	0.038	-10000	0	-0.057	107	107
Rac1/GTP	-0.004	0.02	-10000	0	-0.076	3	3
cytoskeleton organization	0.026	0.068	-10000	0	-0.31	1	1
GIPC1	0.025	0.006	-10000	0	-10000	0	0
Syndecan-4/TFPI	0.038	0.077	-10000	0	-0.32	1	1

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	0.024	0.009	-10000	0	-0.058	1	1
oxygen homeostasis	0	0	-10000	0	-10000	0	0
TCEB2	0.025	0.004	-10000	0	-10000	0	0
TCEB1	0.025	0.005	-10000	0	-10000	0	0
HIF1A/p53	-0.054	0.13	0.16	1	-0.24	43	44
HIF1A	-0.035	0.1	-10000	0	-0.29	20	20
COPS5	0.026	0.004	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.039	0.051	-10000	0	-10000	0	0
FIH (dimer)	0.018	0.012	-10000	0	-10000	0	0
CDKN2A	-0.016	0.03	-10000	0	-0.058	47	47
ARNT/IPAS	0.035	0.011	-10000	0	0	13	13
HIF1AN	0.018	0.012	-10000	0	-10000	0	0
GNB2L1	0.026	0.003	-10000	0	-10000	0	0
HIF1A/ARNT	-0.054	0.13	-10000	0	-0.24	42	42
CUL2	0.018	0.012	-10000	0	-10000	0	0
OS9	0.021	0.01	-10000	0	-10000	0	0
RACK1/Elongin B/Elongin C	0.049	0.014	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF1A/Hsp90	-0.053	0.13	0.16	1	-0.24	43	44
PHD1-3/OS9	0.046	0.034	-10000	0	-0.028	10	10
HIF1A/RACK1/Elongin B/Elongin C	-0.04	0.14	-10000	0	-0.24	42	42
VHL	0.026	0.004	-10000	0	-10000	0	0
HSP90AA1	0.024	0.007	-10000	0	-10000	0	0
HIF1A/JAB1	-0.055	0.13	-10000	0	-0.24	43	43
EGLN3	0.024	0.007	-10000	0	-10000	0	0
EGLN2	0.025	0.006	-10000	0	-10000	0	0
EGLN1	0.025	0.004	-10000	0	-10000	0	0
TP53	0.022	0.017	-10000	0	-0.058	6	6
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.017	0.047	-10000	0	-0.46	1	1
ARNT	0.026	0.004	-10000	0	-10000	0	0
ARD1A	0	0	-10000	0	-10000	0	0
RBX1	0.024	0.007	-10000	0	-10000	0	0
HIF1A/p19ARF	-0.056	0.13	0.16	1	-0.24	43	44

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
GNAO1	0.024	0.007	-10000	0	-10000	0	0
CDC42/GTP	0.035	0.042	-10000	0	-10000	0	0
PLCG1	0.011	0.036	0.075	31	-10000	0	31
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.026	0.003	-10000	0	-10000	0	0
GNAI3	0.026	0.003	-10000	0	-10000	0	0
G12/G13	0.026	0.018	-10000	0	0	49	49
cell migration	0.034	0.041	-10000	0	-10000	0	0
S1PR5	0.023	0.008	-10000	0	-10000	0	0
S1PR4	0.025	0.006	-10000	0	-10000	0	0
MAPK3	0.013	0.038	0.075	36	-10000	0	36
MAPK1	0.015	0.035	0.075	36	-10000	0	36
S1P/S1P5/Gi	0.025	0.037	-10000	0	-0.094	3	3
GNAI1	0.017	0.012	-10000	0	-10000	0	0
CDC42/GDP	0.019	0.003	-10000	0	-10000	0	0
S1P/S1P5/G12	0.022	0.017	-10000	0	0	57	57
RHOA	0.048	0.11	0.19	52	-10000	0	52
S1P/S1P4/Gi	0.027	0.038	-10000	0	-0.094	3	3
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	0.025	0.006	-10000	0	-10000	0	0
S1P/S1P4/G12/G13	0.032	0.024	-10000	0	-0.02	1	1
GNA12	0.017	0.012	-10000	0	-10000	0	0
GNA13	0.026	0.002	-10000	0	-10000	0	0
CDC42	0.026	0.004	-10000	0	-10000	0	0

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.027	0.018	-9999	0	43	43
FBXW11	0.026	0.003	-9999	-9999	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-9999	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.026	0.003	-9999	-9999	0	0
CHUK	0.018	0.012	-9999	-9999	0	0
NF kappa B2 p100/RelB	0.044	0.049	-9999	-9999	0	0
NFKB1	0.026	0.002	-9999	-9999	0	0
MAP3K14	0.026	0	-9999	-9999	0	0
NF kappa B1 p50/RelB	0.036	0.009	-9999	0	9	9
RELB	0.025	0.006	-9999	-9999	0	0
NFKB2	0.018	0.012	-9999	-9999	0	0
NF kappa B2 p52/RelB	0.025	0.016	-9999	0	45	45
regulation of B cell activation	0.024	0.016	-9999	0	45	45

×

amb2 Integrin signaling

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
alphaM/beta2 Integrin/proMMP-2	0.055	0.024	-10000	0	-0.061	4	4
alphaM/beta2 Integrin/GPIbA	0.049	0.019	-10000	0	-0.054	3	3
alphaM/beta2 Integrin/proMMP-9	0.06	0.03	-10000	0	-0.061	4	4
PLAUR	0.015	0.026	-10000	0	-0.058	16	16
HMGB1	0.023	0.012	-10000	0	-0.041	3	3
alphaM/beta2 Integrin/Talin	0.045	0.021	-10000	0	-0.053	2	2
AGER	0.024	0.012	-10000	0	-0.045	4	4
RAP1A	0.026	0.004	-10000	0	-10000	0	0
SELPLG	0.026	0.003	-10000	0	-10000	0	0
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	0.056	0.039	-10000	0	-0.12	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	-0.043	0.031	-10000	0	-0.058	116	116
CYR61	0.023	0.014	-10000	0	-0.058	4	4
TLN1	0.023	0.008	-10000	0	-10000	0	0
Rap1/GTP	0.019	0.051	0.17	1	-0.16	5	6
RHOA	0.026	0.002	-10000	0	-10000	0	0
P-selectin oligomer	0.022	0.012	-10000	0	-0.058	3	3
MYH2	-0.008	0.048	0.19	1	-0.19	3	4
MST1R	0.025	0.007	-10000	0	-0.058	1	1
leukocyte activation during inflammatory response	0.044	0.028	-10000	0	-0.051	3	3
APOB	0.025	0.008	-10000	0	-0.058	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	-0.003	0.04	-10000	0	-0.058	49	49
JAM3	0.026	0.003	-10000	0	-10000	0	0
GP1BA	0.025	0.004	-10000	0	-10000	0	0
alphaM/beta2 Integrin/CTGF	0.044	0.024	-10000	0	-0.054	3	3
alphaM/beta2 Integrin	0.001	0.042	-10000	0	-0.16	3	3
JAM3 homodimer	0.026	0.003	-10000	0	-10000	0	0
ICAM2	0.026	0.002	-10000	0	-10000	0	0
ICAM1	0.017	0.024	-10000	0	-0.058	13	13
phagocytosis triggered by activation of immune response cell surface activating receptor	0.001	0.041	-10000	0	-0.16	3	3
cell adhesion	0.048	0.019	-10000	0	-0.054	3	3
NFKB1	-0.028	0.038	0.17	4	-0.19	2	6
THY1	0.026	0.003	-10000	0	-10000	0	0
RhoA/GDP	0.019	0.002	-10000	0	-10000	0	0
Lipoprotein(a)	0.029	0.01	-10000	0	0	14	14
alphaM/beta2 Integrin/LRP/tPA	0.058	0.031	-10000	0	-0.056	4	4
IL6	-0.022	0.03	0.16	2	-0.18	1	3
ITGB2	0.025	0.01	-10000	0	-0.041	3	3
elevation of cytosolic calcium ion concentration	0.039	0.059	-10000	0	-0.061	25	25
alphaM/beta2 Integrin/JAM2/JAM3	0.062	0.023	-10000	0	-0.055	3	3
JAM2	0.026	0.004	-10000	0	-10000	0	0
alphaM/beta2 Integrin/ICAM1	0.071	0.03	-10000	0	-0.058	3	3
alphaM/beta2 Integrin/uPA/Plg	0.035	0.058	-10000	0	-0.06	27	27
RhoA/GTP	-0.003	0.05	-10000	0	-0.19	4	4
positive regulation of phagocytosis	0.019	0.047	0.14	4	-0.16	2	6
Ron/MSP	0.039	0.004	-10000	0	0	1	1
alphaM/beta2 Integrin/uPAR/uPA	0.041	0.061	-10000	0	-0.061	25	25
alphaM/beta2 Integrin/uPAR	0.049	0.022	-10000	0	-0.054	3	3
PLAU	-0.019	0.036	-10000	0	-0.058	65	65
PLAT	0.019	0.022	-10000	0	-0.058	11	11
actin filament polymerization	-0.009	0.049	0.19	1	-0.18	4	5
MST1	0.026	0.002	-10000	0	-10000	0	0
alphaM/beta2 Integrin/lipoprotein(a)	0.049	0.03	-10000	0	-0.051	3	3
TNF	-0.033	0.045	0.16	4	-0.29	2	6
RAP1B	0.023	0.01	-10000	0	-0.058	1	1
alphaM/beta2 Integrin/uPA	0.033	0.05	-10000	0	-0.061	26	26
fibrinolysis	0.033	0.057	-10000	0	-0.059	27	27
HCK	0.023	0.01	-10000	0	-0.058	1	1
dendritic cell antigen processing and presentation	0.001	0.041	-10000	0	-0.16	3	3
VTN	0.026	0.004	-10000	0	-10000	0	0
alphaM/beta2 Integrin/CYR61	0.049	0.02	-10000	0	-0.054	3	3
LPA	0.02	0.007	-10000	0	-10000	0	0
LRP1	0.024	0.007	-10000	0	-10000	0	0
cell migration	-0.032	0.05	0.16	6	-0.053	117	123
FN1	0.008	0.034	-10000	0	-0.058	31	31
alphaM/beta2 Integrin/Thy1	0.05	0.018	-10000	0	-0.054	3	3
MPO	0.022	0.009	-10000	0	-10000	0	0
KNG1	0.021	0.004	-10000	0	-10000	0	0
RAP1/GDP	0.032	0.011	-10000	0	0	14	14
ROCK1	-0.007	0.053	0.18	2	-0.19	4	6
ELA2	0	0	-10000	0	-10000	0	0
PLG	0.019	0.006	-10000	0	-10000	0	0
CTGF	0.021	0.014	-10000	0	-0.058	3	3
alphaM/beta2 Integrin/Hck	0.046	0.022	-10000	0	-0.054	3	3
ITGAM	0.025	0.01	-10000	0	-0.041	3	3
alphaM/beta2 Integrin/P-Selectin/PSGL1	0.061	0.024	-10000	0	-0.055	3	3
HP	-0.007	0.04	-10000	0	-0.058	56	56
leukocyte adhesion	0.036	0.038	-10000	0	-0.11	3	3
SELP	0.022	0.012	-10000	0	-0.058	3	3

×

Caspase cascade in apoptosis

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
TOP1	-0.025	0.082	-10000	0	-0.3	9	9
ACTA1	-0.058	0.087	-10000	0	-0.28	13	13
NUMA1	-0.022	0.078	-10000	0	-0.3	8	8
SPTAN1	-0.06	0.09	0.18	1	-0.32	11	12
LIMK1	-0.012	0.11	0.17	20	-0.31	8	28
BIRC3	0.024	0.012	-10000	0	-0.058	3	3
BIRC2	0.026	0.002	-10000	0	-10000	0	0
BAX	0.025	0.006	-10000	0	-10000	0	0
CASP10	-0.02	0.017	-10000	0	-0.065	4	4
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.026	0.002	-10000	0	-10000	0	0
PTK2	-0.025	0.083	-10000	0	-0.29	10	10
DIABLO	0.026	0.004	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.059	0.089	0.18	1	-0.32	11	12
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.025	0.004	-10000	0	-10000	0	0
GSN	-0.059	0.088	0.18	1	-0.31	11	12
MADD	0.026	0.004	-10000	0	-10000	0	0
TFAP2A	0.012	0.13	-10000	0	-0.55	7	7
BID	-0.004	0.004	-10000	0	-10000	0	0
MAP3K1	-0.017	0.058	-10000	0	-0.34	3	3
TRADD	0.026	0.003	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.037	0.008	-10000	0	0	7	7
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.058	0.091	0.17	2	-0.32	11	13
CASP9	0.025	0.005	-10000	0	-10000	0	0
DNA repair	0.036	0.065	0.18	12	-10000	0	12
neuron apoptosis	0.016	0.059	-10000	0	-0.66	1	1
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.042	0.092	0.18	2	-0.3	12	14
APAF1	0.026	0.004	-10000	0	-10000	0	0
CASP6	0.009	0.094	-10000	0	-0.83	1	1
TRAF2	0.025	0.005	-10000	0	-10000	0	0
ICAD/CAD	-0.059	0.096	0.25	3	-0.32	11	14
CASP7	-0.059	0.1	-10000	0	-0.21	40	40
KRT18	0.012	0.066	-10000	0	-0.51	2	2
apoptosis	-0.061	0.089	-10000	0	-0.3	12	12
DFFA	-0.06	0.09	0.17	1	-0.32	11	12
DFFB	-0.058	0.091	0.17	2	-0.32	11	13
PARP1	-0.036	0.065	-10000	0	-0.18	12	12
actin filament polymerization	0.007	0.1	0.29	8	-0.16	20	28
TNF	0.025	0.005	-10000	0	-10000	0	0
CYCS	0.005	0.023	-10000	0	-10000	0	0
SATB1	0.004	0.087	-10000	0	-0.78	1	1
SLK	-0.061	0.087	-10000	0	-0.32	11	11
p15 BID/BAX	-0.018	0.057	-10000	0	-0.2	9	9
CASP2	0.046	0.084	0.2	34	-10000	0	34
JNK cascade	0.017	0.058	0.34	3	-10000	0	3
CASP3	-0.059	0.092	-10000	0	-0.29	14	14
LMNB2	0.045	0.079	0.25	3	-10000	0	3
RIPK1	0.025	0.005	-10000	0	-10000	0	0
CASP4	0.01	0.033	-10000	0	-0.058	27	27
Mammalian IAPs/DIABLO	0.065	0.015	-10000	0	-0.028	2	2
negative regulation of DNA binding	0.012	0.13	-10000	0	-0.54	7	7
stress fiber formation	-0.061	0.086	-10000	0	-0.31	11	11
GZMB	-0.019	0.017	0	49	-0.051	20	69
CASP1	0.009	0.001	-10000	0	0	1	1
LMNB1	0.048	0.11	0.26	4	-0.5	2	6
APP	0.016	0.06	-10000	0	-0.66	1	1
TNFRSF1A	0.025	0.005	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	-0.011	0	-10000	0	-10000	0	0
VIM	-0.056	0.093	-10000	0	-0.31	12	12
LMNA	0.048	0.082	0.26	4	-0.27	1	5
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.01	0.032	-10000	0	-0.29	1	1
LRDD	0	0	-10000	0	-10000	0	0
SREBF1	-0.062	0.088	-10000	0	-0.32	11	11
APAF-1/Caspase 9	0.015	0.077	-10000	0	-0.62	2	2
nuclear fragmentation during apoptosis	-0.021	0.077	-10000	0	-0.29	8	8
CFL2	-0.005	0.11	0.16	20	-0.32	7	27
GAS2	-0.062	0.088	-10000	0	-0.31	12	12
positive regulation of apoptosis	0.053	0.09	0.19	17	-0.49	1	18
PRF1	0.011	0.024	-10000	0	-0.058	12	12

×

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

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
MET/RANBP9	0.024	0.019	-10000	0	0	57	57
CRKL	0.043	0.084	0.25	6	-0.23	1	7
mol:PIP3	0.01	0.011	-10000	0	-10000	0	0
AKT1	0.007	0.036	-10000	0	-10000	0	0
PTK2B	0.026	0.004	-10000	0	-10000	0	0
RAPGEF1	0.037	0.086	0.24	8	-0.22	2	10
RANBP10	0.026	0.004	-10000	0	-10000	0	0
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
HGF/MET/SHIP2	0.031	0.026	-10000	0	-10000	0	0
MAP3K5	0.04	0.081	0.24	5	-10000	0	5
HGF/MET/CIN85/CBL/ENDOPHILINS	0.04	0.033	-10000	0	-10000	0	0
AP1	0.024	0.068	0.13	39	-10000	0	39
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.023	0.013	-10000	0	-0.058	3	3
apoptosis	-0.015	0.22	-10000	0	-0.72	12	12
STAT3 (dimer)	0.003	0.031	-10000	0	-10000	0	0
GAB1/CRKL/SHP2/PI3K	0.063	0.085	0.29	2	-0.23	2	4
INPP5D	0.026	0	-10000	0	-10000	0	0
CBL/CRK	0.054	0.082	0.23	5	-0.22	2	7
PTPN11	0.025	0.004	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.023	0.008	-10000	0	-10000	0	0
PTEN	0.016	0.013	-10000	0	-10000	0	0
ELK1	0.11	0.18	0.35	48	-10000	0	48
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	0.001	0.023	-10000	0	-0.13	2	2
PAK1	0.001	0.037	-10000	0	-10000	0	0
HGF/MET/RANBP10	0.031	0.026	-10000	0	-10000	0	0
HRAS	-0.016	0.11	-10000	0	-0.38	11	11
DOCK1	0.031	0.083	0.23	7	-0.22	2	9
GAB1	0.043	0.071	-10000	0	-10000	0	0
CRK	0.045	0.077	0.23	5	-10000	0	5
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.007	0.085	-10000	0	-0.32	9	9
JUN	0.025	0.004	-10000	0	-10000	0	0
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	0.002	0.012	-10000	0	-0.047	7	7
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
cell morphogenesis	0.036	0.1	0.3	10	-10000	0	10
GRB2/SHC	0.048	0.068	0.16	29	-0.097	9	38
FOS	0.024	0.008	-10000	0	-10000	0	0
GLMN	0.002	0.001	-10000	0	-10000	0	0
cell motility	0.11	0.18	0.35	48	-10000	0	48
HGF/MET/MUC20	0.021	0.017	-10000	0	0	60	60
cell migration	0.047	0.067	0.15	29	-0.096	9	38
GRB2	0.025	0.004	-10000	0	-10000	0	0
CBL	0.026	0.002	-10000	0	-10000	0	0
MET/RANBP10	0.023	0.019	-10000	0	0	59	59
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.005	0.027	-10000	0	-10000	0	0
MET/MUC20	0.012	0.009	-10000	0	-10000	0	0
RAP1B	0.042	0.099	0.29	12	-0.22	1	13
RAP1A	0.035	0.085	0.29	5	-0.22	1	6
HGF/MET/RANBP9	0.031	0.026	-10000	0	-10000	0	0
RAF1	0.004	0.13	-10000	0	-0.37	11	11
STAT3	0.003	0.031	-10000	0	-10000	0	0
cell proliferation	0.021	0.084	0.22	5	-0.2	6	11
RPS6KB1	0.004	0.017	-10000	0	-10000	0	0
MAPK3	0.086	0.16	0.4	7	-10000	0	7
MAPK1	0.1	0.19	0.52	11	-10000	0	11
RANBP9	0.026	0.004	-10000	0	-10000	0	0
MAPK8	-0.051	0.14	0.26	2	-0.31	20	22
SRC	-0.008	0.022	0.092	1	-10000	0	1
PI3K	0.047	0.068	0.16	29	-0.097	9	38
MET/Glomulin	0.008	0.024	-10000	0	-0.077	8	8
SOS1	0.026	0	-10000	0	-10000	0	0
MAP2K1	0.002	0.12	-10000	0	-0.35	11	11
MET	0.016	0.013	-10000	0	-10000	0	0
MAP4K1	0.047	0.088	0.26	4	-0.41	1	5
PTK2	0.025	0.006	-10000	0	-10000	0	0
MAP2K2	0.007	0.13	0.29	3	-0.35	10	13
BAD	0	0.034	-10000	0	-10000	0	0
MAP2K4	0.034	0.077	0.24	4	-10000	0	4
SHP2/GRB2/SOS1/GAB1	0.019	0.054	-10000	0	-0.2	1	1
INPPL1	0.026	0	-10000	0	-10000	0	0
PXN	0.026	0.003	-10000	0	-10000	0	0
SH3KBP1	0.026	0	-10000	0	-10000	0	0
HGS	-0.005	0.014	0.072	2	-10000	0	2
PLCgamma1/PKC	0.017	0.006	-10000	0	-10000	0	0
HGF	0.018	0.012	-10000	0	-10000	0	0
RASA1	0.026	0.004	-10000	0	-10000	0	0
NCK1	0.026	0.004	-10000	0	-10000	0	0
PTPRJ	0.026	0.003	-10000	0	-10000	0	0
NCK/PLCgamma1	0.054	0.064	0.16	32	-0.094	8	40
PDPK1	0.014	0.037	0.28	1	-10000	0	1
HGF/MET/SHIP	0.031	0.026	-10000	0	-10000	0	0

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.025	0.008	-10000	0	-0.058	1	1
alphaV beta3 Integrin	0.046	0.011	-10000	0	0	1	1
PTK2	0.002	0.087	-10000	0	-0.24	15	15
positive regulation of JNK cascade	0.007	0.087	-10000	0	-0.24	14	14
CDC42/GDP	0.014	0.13	-10000	0	-0.34	14	14
Rac1/GDP	0.01	0.093	-10000	0	-0.29	8	8
RAP1B	0.023	0.01	-10000	0	-0.058	1	1
RAP1A	0.026	0.004	-10000	0	-10000	0	0
CTNNB1	0.026	0.002	-10000	0	-10000	0	0
CDC42/GTP	0.013	0.11	-10000	0	-0.29	14	14
nectin-3/I-afadin	0.034	0.013	-10000	0	0	18	18
RAPGEF1	-0.012	0.12	0.21	1	-0.34	16	17
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.019	0.13	-10000	0	-0.38	16	16
PDGFB-D/PDGFRB	0.025	0.008	-10000	0	-0.058	1	1
TLN1	-0.015	0.012	-10000	0	-0.059	8	8
Rap1/GTP	-0.004	0.09	-10000	0	-0.26	15	15
IQGAP1	0.026	0.004	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.04	0.024	-10000	0	-0.02	15	15
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.034	0.013	-10000	0	0	18	18
PVR	0.025	0.006	-10000	0	-10000	0	0
Necl-5(dimer)	0.025	0.006	-10000	0	-10000	0	0
mol:GDP	-0.002	0.14	-10000	0	-0.4	15	15
MLLT4	0.023	0.008	-10000	0	-10000	0	0
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
PI3K	0.06	0.04	-10000	0	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.034	0.012	-10000	0	0	17	17
positive regulation of lamellipodium assembly	0.001	0.079	-10000	0	-0.28	7	7
PVRL1	0.026	0.003	-10000	0	-10000	0	0
PVRL3	0.025	0.005	-10000	0	-10000	0	0
PVRL2	0.025	0.006	-10000	0	-10000	0	0
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
CDH1	0.025	0.006	-10000	0	-10000	0	0
CLDN1	0.025	0.005	-10000	0	-10000	0	0
JAM-A/CLDN1	0.053	0.033	-10000	0	-0.028	17	17
SRC	-0.015	0.14	-10000	0	-0.4	16	16
ITGB3	-0.003	0.04	-10000	0	-0.058	50	50
nectin-1(dimer)/I-afadin/I-afadin	0.034	0.012	-10000	0	0	17	17
FARP2	0.006	0.13	-10000	0	-0.37	14	14
RAC1	0.017	0.012	-10000	0	-10000	0	0
CTNNA1	0.026	0.004	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.044	0.02	-10000	0	-10000	0	0
nectin-1/I-afadin	0.034	0.012	-10000	0	0	17	17
nectin-2/I-afadin	0.033	0.014	-10000	0	0	22	22
RAC1/GTP/IQGAP1/filamentous actin	0.023	0.017	-10000	0	0	50	50
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.046	0.018	-10000	0	-10000	0	0
CDC42/GTP/IQGAP1/filamentous actin	0.034	0.007	-10000	0	0	6	6
F11R	0.026	0.003	-10000	0	-10000	0	0
positive regulation of filopodium formation	0.007	0.087	-10000	0	-0.24	14	14
alphaV/beta3 Integrin/Talin	-0.017	0.067	0.18	12	-0.17	2	14
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.033	0.014	-10000	0	0	22	22
nectin-2(dimer)/I-afadin/I-afadin	0.033	0.014	-10000	0	0	22	22
PIP5K1C	-0.013	0.015	-10000	0	-0.057	14	14
VAV2	-0.005	0.17	-10000	0	-0.46	14	14
RAP1/GDP	0.013	0.12	-10000	0	-0.32	14	14
ITGAV	0.026	0.002	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.044	0.02	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin	0.034	0.013	-10000	0	0	18	18
Rac1/GTP	0.005	0.096	-10000	0	-0.33	7	7
PTPRM	0.007	0.003	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin	0.055	0.044	-10000	0	-10000	0	0
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.026	0.004	-10000	0	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	-0.017	0.039	-10000	0	-0.077	41	41
CRKL	0.025	0.006	-10000	0	-10000	0	0
Rac1/GDP	0.013	0.009	-10000	0	-10000	0	0
DOCK1	0.017	0.012	-10000	0	-10000	0	0
ITGA4	0.013	0.031	-10000	0	-0.058	23	23
alpha4/beta7 Integrin/MAdCAM1	0.061	0.025	-10000	0	-0.029	2	2
EPO	0.008	0.027	-10000	0	-0.058	17	17
alpha4/beta7 Integrin	0.041	0.01	-10000	0	0	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.026	0.004	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.031	0.021	0.082	2	0	43	45
EPO/EPOR (dimer)	0.028	0.021	-10000	0	0	50	50
lamellipodium assembly	-0.009	0.068	-10000	0	-0.26	9	9
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
PI3K	0.036	0.01	-10000	0	0	10	10
ARF6	0.025	0.006	-10000	0	-10000	0	0
JAK2	0.001	0.028	-10000	0	-0.087	12	12
PXN	0.026	0.003	-10000	0	-10000	0	0
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
MADCAM1	0.023	0.008	-10000	0	-10000	0	0
cell adhesion	0.059	0.024	-10000	0	-0.029	2	2
CRKL/CBL	0.037	0.009	-10000	0	0	8	8
ITGB1	0.017	0.015	-10000	0	-0.058	2	2
SRC	-0.031	0.027	0.17	2	-10000	0	2
ITGB7	0.026	0.004	-10000	0	-10000	0	0
RAC1	0.017	0.012	-10000	0	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.04	0.036	0.095	7	-0.048	8	15
p130Cas/Crk/Dock1	-0.031	0.041	0.14	5	-10000	0	5
VCAM1	0.007	0.035	-10000	0	-0.058	33	33
RHOA	0.026	0.002	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.041	0.046	-10000	0	-0.029	41	41
BCAR1	-0.034	0.028	0.16	2	-10000	0	2
EPOR	0.025	0.006	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.026	0.002	-10000	0	-10000	0	0
GIT1	0.026	0.004	-10000	0	-10000	0	0
Rac1/GTP	-0.01	0.069	-10000	0	-0.26	9	9

×

FAS signaling pathway (CD95)

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
SPTAN1	-0.017	0.047	0.22	2	-0.19	7	9
RFC1	-0.02	0.038	-10000	0	-0.19	7	7
PRKDC	-0.02	0.038	-10000	0	-0.19	7	7
RIPK1	0.025	0.005	-10000	0	-10000	0	0
CASP7	-0.17	0.28	-10000	0	-0.59	44	44
FASLG/FAS/FADD/FAF1	-0.025	0.059	-10000	0	-0.11	45	45
MAP2K4	-0.074	0.13	0.19	1	-0.25	42	43
mol:ceramide	-0.024	0.068	-10000	0	-0.18	11	11
GSN	-0.015	0.051	0.22	3	-0.19	7	10
FASLG/FAS/FADD/FAF1/Caspase 8	-0.032	0.069	-10000	0	-0.23	7	7
FAS	0.015	0.019	-10000	0	-0.058	6	6
BID	-0.031	0.01	-10000	0	-10000	0	0
MAP3K1	-0.12	0.19	-10000	0	-0.39	45	45
MAP3K7	0.023	0.009	-10000	0	-0.024	1	1
RB1	-0.018	0.043	0.22	1	-0.19	7	8
CFLAR	0.026	0.001	-10000	0	-10000	0	0
HGF/MET	0.031	0.026	-10000	0	-10000	0	0
ARHGDIB	-0.013	0.047	0.22	3	-0.19	5	8
FADD	0.026	0.006	-10000	0	-0.036	1	1
actin filament polymerization	0.014	0.052	0.19	7	-0.19	4	11
NFKB1	0.016	0.022	-10000	0	-10000	0	0
MAPK8	-0.077	0.13	0.18	1	-0.32	17	18
DFFA	-0.017	0.041	0.22	1	-0.19	6	7
DNA fragmentation during apoptosis	-0.014	0.046	0.19	3	-0.19	6	9
FAS/FADD/MET	0.027	0.028	-10000	0	-10000	0	0
CFLAR/RIP1	0.037	0.007	-10000	0	0	5	5
FAIM3	0.007	0.034	-10000	0	-0.058	31	31
FAF1	0.024	0.009	-10000	0	-0.035	1	1
PARP1	-0.018	0.043	0.22	1	-0.19	7	8
DFFB	-0.015	0.045	0.22	2	-0.19	6	8
CHUK	0.009	0.019	-10000	0	-10000	0	0
FASLG	0.022	0.015	-10000	0	-0.053	5	5
FAS/FADD	0.028	0.019	-10000	0	-10000	0	0
HGF	0.018	0.012	-10000	0	-10000	0	0
LMNA	-0.025	0.035	-10000	0	-0.18	7	7
CASP6	-0.02	0.038	-10000	0	-0.19	7	7
CASP10	0.026	0.005	-10000	0	-0.036	1	1
CASP3	-0.01	0.034	-10000	0	-0.22	4	4
PTPN13	0.026	0.002	-10000	0	-10000	0	0
CASP8	-0.029	0.009	-10000	0	-10000	0	0
IL6	-0.018	0.094	-10000	0	-0.94	1	1
MET	0.016	0.013	-10000	0	-10000	0	0
ICAD/CAD	-0.019	0.052	0.3	2	-0.18	6	8
FASLG/FAS/FADD/FAF1/Caspase 10	-0.024	0.069	-10000	0	-0.18	11	11
activation of caspase activity by cytochrome c	-0.03	0.01	-10000	0	-10000	0	0
PAK2	-0.018	0.043	0.22	1	-0.19	7	8
BCL2	0.025	0.005	-10000	0	-10000	0	0

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	0.025	0.006	-10000	0	-10000	0	0
CLTC	0.004	0.093	-10000	0	-0.34	9	9
calcium ion-dependent exocytosis	0.023	0.046	0.092	37	-0.17	1	38
Dynamin 2/GTP	-0.021	0.005	0	8	-0.04	1	9
EXOC4	0.018	0.012	-10000	0	-10000	0	0
CD59	0.004	0.074	-10000	0	-0.29	8	8
CPE	-0.016	0.005	0	13	-10000	0	13
CTNNB1	0.026	0.002	-10000	0	-10000	0	0
membrane fusion	0.028	0.044	0.095	42	-0.075	4	46
CTNND1	-0.025	0.018	0.17	1	-10000	0	1
DNM2	0.025	0.006	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.011	0.056	0.14	3	-0.17	9	12
TSHR	-0.02	0.01	-10000	0	-10000	0	0
INS	-0.006	0.11	-10000	0	-0.48	7	7
BIN1	0.026	0.002	-10000	0	-10000	0	0
mol:Choline	0.028	0.044	0.095	42	-0.075	4	46
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	-0.016	0.005	-10000	0	-0.037	1	1
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.025	0.006	-10000	0	-10000	0	0
mol:Ca2+	-0.021	0.005	0	8	-0.04	1	9
JUP	0.003	0.077	-10000	0	-0.28	9	9
ASAP2/amphiphysin II	0.045	0.019	-10000	0	-0.02	10	10
ARF6/GTP	0.018	0.005	-10000	0	0	9	9
CDH1	0.003	0.077	-10000	0	-0.28	9	9
clathrin-independent pinocytosis	0.018	0.005	-10000	0	0	9	9
MAPK8IP3	0.025	0.006	-10000	0	-10000	0	0
positive regulation of endocytosis	0.018	0.005	-10000	0	0	9	9
EXOC2	0.025	0.005	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	-0.007	0.059	-10000	0	-0.25	5	5
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.026	0.002	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.018	0.077	0.29	8	-10000	0	8
positive regulation of phagocytosis	-0.015	0.006	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.032	0.011	-10000	0	0	16	16
ACAP1	0.033	0.042	0.097	42	-10000	0	42
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	-0.007	0.061	-10000	0	-0.32	5	5
clathrin heavy chain/ACAP1	0.015	0.082	0.18	4	-0.26	9	13
JIP4/KLC1	0.044	0.019	-10000	0	-0.019	12	12
EXOC1	0.024	0.007	-10000	0	-10000	0	0
exocyst	-0.01	0.057	-10000	0	-0.25	5	5
RALA/GTP	0.013	0.009	-10000	0	0	48	48
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.033	0.009	-10000	0	0	10	10
receptor recycling	0.018	0.005	-10000	0	0	9	9
CTNNA1	-0.025	0.018	0.17	1	-10000	0	1
NME1	-0.016	0.005	-10000	0	-0.037	1	1
clathrin coat assembly	0.007	0.094	0.25	1	-0.34	9	10
IL2RA	-0.014	0.087	-10000	0	-0.35	8	8
VAMP3	-0.015	0.006	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	0.021	0.075	-10000	0	-0.25	9	9
EXOC6	0.018	0.012	-10000	0	-10000	0	0
PLD1	0.003	0.011	-10000	0	-0.053	5	5
PLD2	0.003	0.011	-10000	0	-0.053	5	5
EXOC5	0.024	0.007	-10000	0	-10000	0	0
PIP5K1C	0.008	0.053	-10000	0	-0.17	9	9
SDC1	0.002	0.077	-10000	0	-0.28	9	9
ARF6/GDP	0.02	0.007	-10000	0	-0.037	1	1
EXOC7	0.026	0.004	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.02	0.079	-10000	0	-0.3	8	8
mol:Phosphatidic acid	0.028	0.044	0.095	42	-0.075	4	46
endocytosis	-0.043	0.018	0.02	10	-10000	0	10
SCAMP2	0.025	0.004	-10000	0	-10000	0	0
ADRB2	0	0.09	0.23	1	-0.33	9	10
EXOC3	0.025	0.005	-10000	0	-10000	0	0
ASAP2	0.026	0.003	-10000	0	-10000	0	0
Dynamin 2/GDP	0.02	0.013	-10000	0	-0.04	1	1
KLC1	0.025	0.006	-10000	0	-10000	0	0
AVPR2	0.003	0.094	0.2	4	-0.33	9	13
RALA	0.018	0.012	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.008	0.077	0.2	1	-0.29	8	9

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.024	0.007	-10000	0	-10000	0	0
GNB1/GNG2	-0.022	0.041	-10000	0	-0.17	9	9
AKT1	0.011	0.1	0.24	6	-0.29	6	12
EGF	0.026	0.002	-10000	0	0	1	1
mol:TXA2	0	0	-10000	0	-10000	0	0
FGR	-0.017	0.069	0.26	7	-10000	0	7
mol:Ca2+	0.019	0.1	0.3	4	-0.27	8	12
LYN	-0.015	0.076	0.28	8	-10000	0	8
RhoA/GTP	-0.002	0.033	0.085	1	-0.12	5	6
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	0.003	0.1	0.28	4	-0.3	9	13
GNG2	0.025	0.006	-10000	0	-10000	0	0
ARRB2	0.026	0.004	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.004	0.06	-10000	0	-0.34	3	3
G beta5/gamma2	-0.025	0.054	-10000	0	-0.23	8	8
PRKCH	0.01	0.11	0.29	4	-0.29	10	14
DNM1	0.016	0.013	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin3	0.005	0.012	-10000	0	-10000	0	0
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
PTGDR	0.023	0.009	-10000	0	-0.058	1	1
G12 family/GTP	-0.003	0.067	-10000	0	-0.26	5	5
ADRBK1	0.026	0.002	-10000	0	-10000	0	0
ADRBK2	0.025	0.006	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0.034	0.008	-10000	0	0	7	7
mol:GDP	-0.013	0.092	0.3	4	-0.3	4	8
mol:NADP	0.018	0.012	-10000	0	-10000	0	0
RAB11A	0.025	0.004	-10000	0	-10000	0	0
PRKG1	0.019	0.012	-10000	0	-10000	0	0
mol:IP3	0.017	0.12	0.32	4	-0.34	8	12
cell morphogenesis	0.034	0.008	-10000	0	0	7	7
PLCB2	0.013	0.15	0.34	4	-0.45	8	12
mol:cGMP	0	0	-10000	0	-10000	0	0
BLK	-0.016	0.076	0.28	8	-0.14	1	9
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.023	0.05	0.24	4	-0.14	1	5
RHOA	0.026	0.002	-10000	0	-10000	0	0
PTGIR	0.022	0.015	-10000	0	-0.058	4	4
PRKCB1	0.013	0.11	0.29	4	-0.31	11	15
GNAQ	0.025	0.005	-10000	0	-10000	0	0
mol:L-citrulline	0.018	0.012	-10000	0	-10000	0	0
TXA2/TXA2-R family	0.002	0.14	0.33	4	-0.44	9	13
LCK	-0.018	0.077	0.28	8	-0.14	1	9
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.02	0.032	0.16	1	-0.14	1	2
TXA2-R family/G12 family/GDP/G beta/gamma	0.002	0.062	-10000	0	-0.39	3	3
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.016	0.036	0.16	1	-0.14	1	2
MAPK14	0.001	0.074	0.23	4	-0.21	8	12
TGM2/GTP	0.018	0.12	0.36	1	-0.37	7	8
MAPK11	0	0.073	0.23	4	-0.21	8	12
ARHGEF1	-0.01	0.04	-10000	0	-0.16	5	5
GNAI2	0.026	0.003	-10000	0	-10000	0	0
JNK cascade	0.007	0.11	0.31	4	-0.33	9	13
RAB11/GDP	0.024	0.01	-10000	0	-0.031	4	4
ICAM1	0.007	0.088	0.25	4	-0.25	9	13
cAMP biosynthetic process	0.012	0.11	0.31	4	-0.31	8	12
Gq family/GTP/EBP50	0.005	0.04	0.24	1	-0.21	4	5
actin cytoskeleton reorganization	0.034	0.008	-10000	0	0	7	7
SRC	-0.023	0.05	0.24	4	-10000	0	4
GNB5	0.026	0.004	-10000	0	-10000	0	0
GNB1	0.025	0.006	-10000	0	-10000	0	0
EGF/EGFR	0.033	0.087	0.25	14	-10000	0	14
VCAM1	0.007	0.09	0.25	4	-0.26	9	13
TP beta/Gq family/GDP/G beta5/gamma2	-0.004	0.06	-10000	0	-0.34	3	3
platelet activation	0.007	0.098	0.31	4	-0.26	9	13
PGI2/IP	0.019	0.006	0.041	4	0	9	13
PRKACA	0.005	0.023	-10000	0	-0.079	10	10
Gq family/GDP/G beta5/gamma2	-0.003	0.056	-10000	0	-0.31	3	3
TXA2/TP beta/beta Arrestin2	-0.066	0.13	-10000	0	-0.3	34	34
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.016	0.021	-10000	0	-0.087	11	11
mol:DAG	0.016	0.12	0.32	4	-0.34	11	15
EGFR	0.007	0.016	-10000	0	-0.058	4	4
TXA2/TP alpha	0.011	0.14	0.35	4	-0.41	8	12
Gq family/GTP	0.002	0.017	-10000	0	-0.21	1	1
YES1	-0.014	0.076	0.28	8	-0.14	1	9
GNAI2/GTP	-0.017	0.031	-10000	0	-0.15	1	1
PGD2/DP	0.018	0.005	0.041	1	0	9	10
SLC9A3R1	0.026	0.002	-10000	0	-10000	0	0
FYN	-0.012	0.076	0.28	8	-0.14	1	9
mol:NO	0.018	0.012	-10000	0	-10000	0	0
GNA15	0.025	0.006	-10000	0	-10000	0	0
PGK/cGMP	0.02	0.018	-10000	0	0	66	66
RhoA/GDP	0.024	0.009	-10000	0	-0.031	4	4
TP alpha/TGM2/GDP/G beta/gamma	0.029	0.041	0.18	1	-0.15	1	2
NOS3	0.018	0.012	-10000	0	-10000	0	0
RAC1	0.017	0.012	-10000	0	-10000	0	0
PRKCA	0.012	0.11	0.29	4	-0.29	11	15
PRKCB	-0.009	0.097	0.27	4	-0.3	9	13
PRKCE	0.01	0.11	0.28	4	-0.3	9	13
PRKCD	0.011	0.11	0.29	4	-0.32	9	13
PRKCG	-0.021	0.09	0.34	1	-0.31	10	11
muscle contraction	0.001	0.14	0.32	4	-0.4	10	14
PRKCZ	0.001	0.1	0.26	6	-0.3	9	15
ARR3	0.02	0.002	-10000	0	-10000	0	0
TXA2/TP beta	0.016	0.038	0.17	1	-0.15	1	2
PRKCQ	-0.001	0.1	0.25	5	-0.3	10	15
MAPKKK cascade	0.005	0.13	0.31	4	-0.37	11	15
SELE	0.008	0.09	0.25	4	-0.26	9	13
TP beta/GNAI2/GDP/G beta/gamma	0.031	0.041	0.18	1	-0.15	1	2
ROCK1	0.025	0.005	-10000	0	-10000	0	0
GNA14	0.025	0.005	-10000	0	-10000	0	0
chemotaxis	-0.003	0.15	0.32	4	-0.5	9	13
GNA12	0.017	0.012	-10000	0	-10000	0	0
GNA13	0.026	0.002	-10000	0	-10000	0	0
GNA11	0.025	0.006	-10000	0	-10000	0	0
Rac1/GTP	0.013	0.009	-10000	0	0	49	49

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.067	0.048	0.16	1	-0.14	20	21
HDAC7	0.025	0.006	-10000	0	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	0.018	0.11	-10000	0	-0.32	2	2
SMAD4	0.025	0.005	-10000	0	-10000	0	0
ID2	-0.07	0.056	0.18	2	-0.17	7	9
AP1	0.035	0.013	-10000	0	-10000	0	0
ABCG2	-0.071	0.055	0.18	2	-0.17	7	9
HIF1A	-0.018	0.032	-10000	0	-0.049	36	36
TFF3	-0.07	0.059	0.19	2	-0.18	7	9
GATA2	0.026	0.003	-10000	0	-10000	0	0
AKT1	-0.016	0.033	-10000	0	-0.091	2	2
response to hypoxia	-0.013	0.014	-10000	0	-0.071	2	2
MCL1	-0.072	0.052	0.18	1	-0.17	7	8
NDRG1	-0.071	0.053	0.18	1	-0.17	7	8
SERPINE1	-0.05	0.058	0.18	1	-0.17	6	7
FECH	-0.067	0.057	0.18	2	-0.17	7	9
FURIN	-0.069	0.056	0.18	2	-0.17	8	10
NCOA2	0.026	0.004	-10000	0	-10000	0	0
EP300	-0.006	0.024	-10000	0	-0.23	1	1
HMOX1	-0.069	0.06	0.18	2	-0.18	9	11
BHLHE40	-0.07	0.056	0.18	2	-0.17	8	10
BHLHE41	-0.067	0.057	0.18	2	-0.17	7	9
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.06	0.052	-10000	0	-0.077	6	6
ENG	-0.037	0.054	0.18	6	-10000	0	6
JUN	0.026	0.004	-10000	0	-10000	0	0
RORA	-0.069	0.056	0.18	2	-0.17	7	9
ABCB1	0.002	0.032	-10000	0	-0.34	1	1
TFRC	-0.068	0.057	0.18	2	-0.17	7	9
CXCR4	-0.073	0.057	0.18	2	-0.18	8	10
TF	-0.066	0.056	0.18	2	-0.17	9	11
CITED2	-0.063	0.057	0.18	2	-0.18	6	8
HIF1A/ARNT	0.13	0.1	-10000	0	-0.19	5	5
LDHA	0.01	0.07	-10000	0	-0.45	3	3
ETS1	-0.069	0.056	0.18	2	-0.17	7	9
PGK1	-0.071	0.055	0.18	2	-0.17	7	9
NOS2	-0.071	0.057	0.18	2	-0.17	9	11
ITGB2	-0.07	0.056	0.18	2	-0.17	7	9
ALDOA	-0.07	0.056	0.18	2	-0.17	7	9
Cbp/p300/CITED2	-0.06	0.066	0.18	1	-0.3	2	3
FOS	0.024	0.008	-10000	0	-10000	0	0
HK2	-0.071	0.056	0.18	2	-0.18	7	9
SP1	0.027	0.004	-10000	0	-10000	0	0
GCK	-0.007	0.08	-10000	0	-0.75	1	1
HK1	-0.052	0.06	0.18	2	-0.17	6	8
NPM1	-0.071	0.055	0.18	2	-0.17	7	9
EGLN1	-0.071	0.052	0.18	1	-0.17	7	8
CREB1	0.028	0	-10000	0	-10000	0	0
PGM1	-0.068	0.056	0.18	2	-0.17	8	10
SMAD3	0.026	0.004	-10000	0	-10000	0	0
EDN1	-0.026	0.084	-10000	0	-0.42	2	2
IGFBP1	-0.047	0.055	0.18	1	-0.18	4	5
VEGFA	-0.063	0.069	-10000	0	-0.32	2	2
HIF1A/JAB1	0.011	0.036	-10000	0	-0.04	46	46
CP	-0.073	0.058	0.18	2	-0.17	9	11
CXCL12	-0.051	0.059	0.18	2	-0.17	7	9
COPS5	0.026	0.004	-10000	0	-10000	0	0
SMAD3/SMAD4	0.037	0.009	-10000	0	0	9	9
BNIP3	-0.049	0.06	0.18	2	-0.17	6	8
EGLN3	-0.065	0.057	0.18	2	-0.18	6	8
CA9	-0.073	0.062	0.18	2	-0.18	11	13
TERT	-0.076	0.061	0.18	2	-0.18	10	12
ENO1	-0.067	0.053	0.18	1	-0.17	8	9
PFKL	-0.07	0.056	0.18	2	-0.17	9	11
NCOA1	0.026	0.003	-10000	0	-10000	0	0
ADM	-0.072	0.058	0.18	2	-0.17	10	12
ARNT	-0.02	0.031	-10000	0	-0.048	37	37
HNF4A	0.019	0.014	-10000	0	-0.12	1	1
ADFP	-0.067	0.048	0.16	1	-0.14	20	21
SLC2A1	-0.061	0.064	-10000	0	-0.31	2	2
LEP	-0.046	0.053	0.18	1	-0.16	5	6
HIF1A/ARNT/Cbp/p300	0.007	0.11	-10000	0	-0.33	2	2
EPO	-0.014	0.063	-10000	0	-0.33	2	2
CREBBP	-0.007	0.024	-10000	0	-0.23	1	1
HIF1A/ARNT/Cbp/p300/HDAC7	0.016	0.11	-10000	0	-0.33	2	2
PFKFB3	-0.05	0.06	0.18	2	-0.17	6	8
NT5E	-0.065	0.057	0.18	2	-0.17	8	10

×

IL2 signaling events mediated by PI3K

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
BCL2L1	0.006	0.048	-10000	0	-10000	0	0
UGCG	-0.003	0.095	-10000	0	-0.57	4	4
AKT1/mTOR/p70S6K/Hsp90/TERT	0.001	0.085	0.22	1	-0.3	6	7
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.002	0.094	-10000	0	-0.56	4	4
mol:DAG	-0.22	0.37	-10000	0	-0.79	43	43
CaM/Ca2+/Calcineurin A alpha-beta B1	0.01	0.066	0.24	1	-10000	0	1
FRAP1	0.001	0.066	0.26	1	-10000	0	1
FOXO3	-0.003	0.066	0.22	2	-10000	0	2
AKT1	-0.001	0.068	0.26	1	-10000	0	1
GAB2	0.026	0.002	-10000	0	-10000	0	0
SMPD1	-0.006	0.1	-10000	0	-0.56	5	5
SGMS1	-0.16	0.27	-10000	0	-0.58	43	43
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	-0.015	0.004	-10000	0	-10000	0	0
CALM1	0.024	0.007	-10000	0	-10000	0	0
cell proliferation	-0.069	0.16	-10000	0	-0.33	38	38
EIF3A	0.018	0.012	-10000	0	-10000	0	0
PI3K	0.037	0.01	-10000	0	-10000	0	0
RPS6KB1	0.019	0.009	-10000	0	-10000	0	0
mol:sphingomyelin	-0.22	0.37	-10000	0	-0.79	43	43
natural killer cell activation	0	0	-10000	0	-10000	0	0
JAK3	0.026	0.005	-10000	0	-10000	0	0
PIK3R1	0.026	0.005	-10000	0	-10000	0	0
JAK1	0.026	0.005	-10000	0	-10000	0	0
NFKB1	0.026	0.002	-10000	0	-10000	0	0
MYC	0.005	0.075	0.24	3	-10000	0	3
MYB	0.012	0.017	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.006	0.059	-10000	0	-0.25	1	1
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.035	0.025	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.006	0.058	-10000	0	-0.25	1	1
Rac1/GDP	-0.014	0.01	-10000	0	-10000	0	0
T cell proliferation	-0.011	0.054	0.19	1	-0.24	1	2
SHC1	0.024	0.013	-10000	0	-0.058	3	3
RAC1	0.017	0.012	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.001	0	-10000	0	-10000	0	0
PRKCZ	-0.011	0.054	0.19	1	-0.24	1	2
NF kappa B1 p50/RelA	0.017	0.075	0.25	1	-10000	0	1
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.005	0.036	-10000	0	-0.18	1	1
HSP90AA1	0.024	0.007	-10000	0	-10000	0	0
RELA	0.026	0.003	-10000	0	-10000	0	0
IL2RA	-0.021	0.036	-10000	0	-0.058	68	68
IL2RB	0.019	0.021	-10000	0	-0.058	9	9
TERT	-0.023	0.04	-10000	0	-0.058	82	82
E2F1	0.02	0.007	-10000	0	-10000	0	0
SOS1	0.026	0	-10000	0	-10000	0	0
RPS6	0.022	0.011	-10000	0	-0.058	1	1
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.026	0.004	-10000	0	-10000	0	0
IL2RG	0.02	0.022	-10000	0	-0.058	11	11
actin cytoskeleton organization	-0.011	0.054	0.19	1	-0.24	1	2
GRB2	0.026	0.004	-10000	0	-10000	0	0
IL2	0.021	0.002	-10000	0	-10000	0	0
PIK3CA	0.026	0.004	-10000	0	-10000	0	0
Rac1/GTP	0.029	0.025	-10000	0	-10000	0	0
LCK	0.003	0.037	-10000	0	-0.058	40	40
BCL2	0.002	0.067	0.4	1	-10000	0	1

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.018	0.008	-10000	0	-10000	0	0
NFATC2	-0.017	0.008	-10000	0	-10000	0	0
NFATC3	-0.018	0.007	-10000	0	-10000	0	0
CD40LG	-0.029	0.072	0.17	13	-10000	0	13
PTGS2	-0.027	0.073	0.17	13	-10000	0	13
JUNB	0.025	0.006	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0.015	0.011	-10000	0	-0.019	11	11
CaM/Ca2+	0.015	0.011	-10000	0	-0.019	11	11
CALM1	0.023	0.01	-10000	0	-0.025	3	3
JUN	0.024	0.009	-10000	0	-0.025	4	4
mol:Ca2+	-0.001	0.002	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.016	0.005	-10000	0	0	12	12
FOSL1	-0.003	0.04	-10000	0	-0.058	50	50
CREM	0.018	0.012	-10000	0	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.007	0.064	0.14	13	-10000	0	13
FOS	0.023	0.009	-10000	0	-0.024	2	2
IFNG	-0.03	0.062	0.15	10	-10000	0	10
AP-1/NFAT1-c-4	-0.011	0.071	0.16	12	-0.12	3	15
FASLG	-0.027	0.073	0.18	12	-10000	0	12
NFAT1-c-4/ICER1	-0.03	0.019	-10000	0	-10000	0	0
IL2RA	-0.03	0.064	0.18	8	-10000	0	8
FKBP12/FK506	0.018	0.005	-10000	0	0	12	12
CSF2	-0.029	0.072	0.17	13	-10000	0	13
JunB/Fra1/NFAT1-c-4	-0.007	0.064	0.14	13	-10000	0	13
IL4	-0.029	0.072	0.17	12	-10000	0	12
IL2	0.011	0.073	-10000	0	-0.87	1	1
IL3	0.015	0.067	-10000	0	-0.55	2	2
FKBP1A	0.024	0.007	-10000	0	-10000	0	0
BATF3	0.024	0.011	-10000	0	-0.058	2	2
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.026	0.004	-10000	0	-10000	0	0

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	0.023	0.014	-10000	0	-0.032	9	9
NFATC2	0.039	0.062	-10000	0	-0.2	8	8
NFATC3	0.008	0.059	-10000	0	-0.22	8	8
CD40LG	-0.034	0.12	0.28	2	-0.48	8	10
ITCH	-0.018	0.016	-10000	0	-0.052	26	26
CBLB	-0.019	0.015	-10000	0	-0.052	26	26
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.046	0.12	-10000	0	-0.6	3	3
JUNB	0.025	0.006	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0.02	0.015	-10000	0	-0.056	2	2
T cell anergy	-0.019	0.049	-10000	0	-0.14	19	19
TLE4	0	0.034	-10000	0	-0.13	6	6
Jun/NFAT1-c-4/p21SNFT	0.044	0.14	-10000	0	-0.52	8	8
AP-1/NFAT1-c-4	0.049	0.14	-10000	0	-0.52	8	8
IKZF1	0.001	0.025	-10000	0	-0.13	3	3
T-helper 2 cell differentiation	-0.062	0.15	-10000	0	-0.55	4	4
AP-1/NFAT1	0.052	0.05	-10000	0	-10000	0	0
CALM1	0.013	0.029	-10000	0	-0.047	27	27
EGR2	-0.015	0.12	-10000	0	-0.51	8	8
EGR3	-0.029	0.19	-10000	0	-0.81	8	8
NFAT1/FOXP3	0.048	0.049	-10000	0	-0.14	8	8
EGR1	0.026	0.005	-10000	0	-0.025	1	1
JUN	0.014	0.021	-10000	0	-0.036	1	1
EGR4	0.011	0.013	-10000	0	-0.022	2	2
mol:Ca2+	0.002	0.001	-10000	0	-10000	0	0
GBP3	-0.005	0.04	-10000	0	-0.14	8	8
FOSL1	-0.003	0.04	-10000	0	-0.058	50	50
NFAT1-c-4/MAF/IRF4	0.046	0.14	-10000	0	-0.5	8	8
DGKA	-0.001	0.037	-10000	0	-0.13	8	8
CREM	0.018	0.012	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	0.036	0.14	-10000	0	-0.54	8	8
CTLA4	-0.022	0.029	-10000	0	-0.12	8	8
NFAT1-c-4 (dimer)/EGR1	0.036	0.14	-10000	0	-0.54	8	8
NFAT1-c-4 (dimer)/EGR4	0.001	0.14	-10000	0	-0.54	8	8
FOS	0.013	0.02	-10000	0	-0.03	2	2
IFNG	0.002	0.058	-10000	0	-0.4	1	1
T cell activation	0.008	0.085	0.32	1	-10000	0	1
MAF	0.025	0.005	-10000	0	-10000	0	0
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.011	0.1	0.45	8	-10000	0	8
TNF	-0.033	0.12	-10000	0	-0.51	8	8
FASLG	-0.047	0.18	-10000	0	-0.75	8	8
TBX21	0.022	0.019	-10000	0	-0.058	8	8
BATF3	0.024	0.011	-10000	0	-0.058	2	2
PRKCQ	0.019	0.012	-10000	0	-10000	0	0
PTPN1	0	0.036	-10000	0	-0.13	7	7
NFAT1-c-4/ICER1	0.022	0.14	-10000	0	-0.54	8	8
GATA3	0	0.033	-10000	0	-0.058	32	32
T-helper 1 cell differentiation	0.001	0.059	-10000	0	-0.4	1	1
IL2RA	-0.019	0.13	-10000	0	-0.61	3	3
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.002	0.038	-10000	0	-0.13	8	8
E2F1	0.025	0.008	-10000	0	-10000	0	0
PPARG	0.026	0.002	-10000	0	-10000	0	0
SLC3A2	-0.001	0.037	-10000	0	-0.13	8	8
IRF4	0.025	0.008	-10000	0	-0.058	1	1
PTGS2	-0.033	0.12	0.28	2	-0.48	8	10
CSF2	-0.035	0.12	0.28	2	-0.48	8	10
JunB/Fra1/NFAT1-c-4	0.05	0.14	-10000	0	-0.52	8	8
IL4	-0.061	0.15	-10000	0	-0.56	4	4
IL5	-0.035	0.12	0.28	2	-0.48	8	10
IL2	0.008	0.086	0.32	1	-10000	0	1
IL3	0.012	0.041	-10000	0	-0.39	1	1
RNF128	-0.01	0.006	-10000	0	-10000	0	0
NFATC1	-0.011	0.11	-10000	0	-0.45	8	8
CDK4	0.017	0.079	0.33	8	-10000	0	8
PTPRK	0	0.032	-10000	0	-0.14	5	5
IL8	-0.036	0.12	0.29	2	-0.48	8	10
POU2F1	0.026	0.004	-10000	0	-10000	0	0

×

Signaling events mediated by PRL

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
CCNE1	0.024	0.007	-10000	0	-10000	0	0
mol:Halofuginone	0.001	0	-10000	0	-10000	0	0
ITGA1	0.019	0.022	-10000	0	-0.058	11	11
CDKN1A	0.009	0.028	-10000	0	-0.33	1	1
PRL-3/alpha Tubulin	0.036	0.01	-10000	0	0	11	11
mol:Ca2+	-0.025	0.007	0	10	-10000	0	10
AGT	0.025	0.005	-10000	0	-10000	0	0
CCNA2	-0.024	0.045	0.16	8	-10000	0	8
TUBA1B	0.025	0.005	-10000	0	-10000	0	0
EGR1	-0.009	0.001	-10000	0	-10000	0	0
CDK2/Cyclin E1	0.045	0.058	-10000	0	-0.31	3	3
MAPK3	-0.021	0.005	0	9	-10000	0	9
PRL-2 /Rab GGTase beta	0.038	0.006	-10000	0	0	4	4
MAPK1	-0.02	0.006	0	14	-10000	0	14
PTP4A1	-0.018	0.007	-10000	0	-10000	0	0
PTP4A3	0.025	0.006	-10000	0	-10000	0	0
PTP4A2	0.025	0.004	-10000	0	-10000	0	0
ITGB1	-0.015	0.011	0	48	-0.047	1	49
SRC	0.024	0.007	-10000	0	-10000	0	0
RAC1	0.007	0.006	-10000	0	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0.035	0.011	-10000	0	0	13	13
PRL-1/ATF-5	-0.014	0.043	0.18	7	-10000	0	7
RABGGTA	0.024	0.007	-10000	0	-10000	0	0
BCAR1	-0.024	0.007	0	12	-10000	0	12
RHOC	0.009	0.03	-10000	0	-0.33	1	1
RHOA	0.008	0.028	-10000	0	-0.33	1	1
cell motility	0.021	0.044	-10000	0	-0.31	1	1
PRL-1/alpha Tubulin	-0.012	0.048	0.18	9	-10000	0	9
PRL-3/alpha1 Integrin	0.038	0.011	-10000	0	0	9	9
ROCK1	0.019	0.043	-10000	0	-0.32	1	1
RABGGTB	0.026	0.004	-10000	0	-10000	0	0
CDK2	-0.017	0.041	-10000	0	-0.058	73	73
mitosis	-0.017	0.007	-10000	0	-10000	0	0
ATF5	0.025	0.006	-10000	0	-10000	0	0

×

Aurora A 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
Aurora A/GADD45A	0.026	0.027	-10000	0	-0.13	2	2
BIRC5	-0.056	0.013	-10000	0	-0.058	143	143
NFKBIA	-0.016	0.015	0.081	1	-0.14	1	2
CPEB1	0.025	0.005	-10000	0	-10000	0	0
AKT1	-0.014	0.025	0.24	1	-0.14	1	2
NDEL1	0.026	0.004	-10000	0	-10000	0	0
Aurora A/BRCA1	0.018	0.02	-10000	0	-0.12	2	2
NDEL1/TACC3	0.041	0.028	-10000	0	-0.12	2	2
GADD45A	0.024	0.013	-10000	0	-0.058	3	3
GSK3B	-0.017	0.018	0.075	1	-10000	0	1
PAK1/Aurora A	0.026	0.027	-10000	0	-0.13	2	2
MDM2	0.023	0.008	-10000	0	-10000	0	0
JUB	0	0	-10000	0	-10000	0	0
TPX2	-0.031	0.016	-10000	0	-0.047	66	66
TP53	0.003	0.042	0.15	1	-0.21	5	6
DLG7	-0.008	0.009	0.089	1	-10000	0	1
AURKAIP1	0.025	0.006	-10000	0	-10000	0	0
ARHGEF7	0.025	0.006	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.043	0.03	-10000	0	-0.13	2	2
G2/M transition of mitotic cell cycle	0.018	0.02	-10000	0	-0.12	2	2
AURKA	-0.011	0.018	0.12	1	-0.16	1	2
AURKB	0.018	0.026	-10000	0	-0.15	3	3
CDC25B	0.004	0.014	0.09	1	-0.13	1	2
G2/M transition checkpoint	-0.009	0.014	0.072	1	-0.11	2	3
mRNA polyadenylation	0.017	0.02	-10000	0	-0.12	2	2
Aurora A/CPEB	0.017	0.02	-10000	0	-0.12	2	2
Aurora A/TACC1/TRAP/chTOG	0.052	0.028	-10000	0	-0.12	1	1
BRCA1	0.025	0.007	-10000	0	-0.058	1	1
centrosome duplication	0.026	0.027	-10000	0	-0.13	2	2
regulation of centrosome cycle	0.04	0.028	-10000	0	-0.12	2	2
spindle assembly	0.051	0.027	-10000	0	-0.12	1	1
TDRD7	0.025	0.005	-10000	0	-10000	0	0
Aurora A/RasGAP/Survivin	0.07	0.037	0.18	4	-0.13	2	6
CENPA	0.025	0.029	-10000	0	-0.24	1	1
Aurora A/PP2A	0.027	0.024	-10000	0	-0.14	1	1
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	-0.001	0.029	0.12	1	-0.16	2	3
negative regulation of DNA binding	0.003	0.042	0.15	1	-0.21	5	6
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.036	0.01	-10000	0	0	10	10
RASA1	0.026	0.004	-10000	0	-10000	0	0
Ajuba/Aurora A	-0.009	0.014	0.073	1	-0.11	2	3
mitotic prometaphase	-0.007	0.012	0.076	3	-10000	0	3
proteasomal ubiquitin-dependent protein catabolic process	-0.011	0.018	0.12	1	-0.16	1	2
TACC1	0.026	0.004	-10000	0	-10000	0	0
TACC3	0.007	0.035	-10000	0	-0.058	33	33
Aurora A/Antizyme1	0.037	0.028	-10000	0	-0.13	2	2
Aurora A/RasGAP	0.027	0.023	-10000	0	-0.13	1	1
OAZ1	0.025	0.006	-10000	0	-10000	0	0
RAN	0.026	0.004	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	-0.018	0.016	0.075	1	-10000	0	1
GIT1	0.026	0.004	-10000	0	-10000	0	0
GIT1/beta-PIX/PAK1	0.049	0.015	-10000	0	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.031	0.016	-10000	0	-0.046	66	66
PPP2R5D	0.026	0.004	-10000	0	-10000	0	0
Aurora A/TPX2	-0.028	0.024	0.064	4	-0.14	2	6
PAK1	0.026	0.004	-10000	0	-10000	0	0
CKAP5	0.026	0.004	-10000	0	-10000	0	0

×

BMP receptor signaling

Figure S43. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S43. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	0.046	0.051	-9999	-0.049	6	6
SMAD6-7/SMURF1	0.034	0.025	-9999	-10000	0	0
NOG	0.026	0.002	-9999	-10000	0	0
SMAD9	-0.024	0.14	-9999	-0.45	13	13
SMAD4	0.025	0.005	-9999	-10000	0	0
SMAD5	-0.027	0.08	-9999	-0.31	9	9
BMP7/USAG1	0.015	0.019	-9999	0	90	90
SMAD5/SKI	-0.022	0.09	-9999	-0.29	12	12
SMAD1	0.002	0.054	-9999	-0.28	1	1
BMP2	0.022	0.014	-9999	-0.058	3	3
SMAD1/SMAD1/SMAD4	0.013	0.05	-9999	-0.26	1	1
BMPR1A	0.018	0.012	-9999	-10000	0	0
BMPR1B	0.026	0.002	-9999	-10000	0	0
BMPR1A-1B/BAMBI	0.036	0.025	-9999	-10000	0	0
AHSG	0.025	0.005	-9999	-10000	0	0
CER1	0.008	0.031	-9999	-0.058	24	24
BMP2-4/CER1	0.044	0.025	-9999	-0.043	1	1
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	0.002	0.05	-9999	-0.2	7	7
BMP2-4 (homodimer)	0.034	0.014	-9999	0	21	21
RGMB	0.026	0.004	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	0.038	0.044	-9999	-0.028	46	46
RGMA	0.026	0.003	-9999	-10000	0	0
SMURF1	0.018	0.012	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.012	0.052	-9999	-0.18	6	6
BMP2-4/USAG1	0.02	0.026	-9999	-10000	0	0
SMAD6/SMURF1/SMAD5	-0.013	0.078	-9999	-0.29	9	9
SOSTDC1	0.011	0.013	-9999	-10000	0	0
BMP7/BMPR2/BMPR1A-1B	0.04	0.041	-9999	-0.028	33	33
SKI	0.025	0.006	-9999	-10000	0	0
BMP6 (homodimer)	0.025	0.005	-9999	-10000	0	0
HFE2	0.022	0.004	-9999	-10000	0	0
ZFYVE16	0.026	0.004	-9999	-10000	0	0
MAP3K7	0.024	0.008	-9999	-10000	0	0
BMP2-4/CHRD	0.045	0.021	-9999	-0.043	1	1
SMAD5/SMAD5/SMAD4	-0.023	0.09	-9999	-0.29	12	12
MAPK1	0.025	0.006	-9999	-10000	0	0
TAK1/TAB family	0.006	0.046	-9999	-0.16	4	4
BMP7 (homodimer)	0.024	0.008	-9999	-10000	0	0
NUP214	0.025	0.006	-9999	-10000	0	0
BMP6/FETUA	0.036	0.009	-9999	0	9	9
SMAD1/SKI	0.01	0.064	-9999	-0.24	2	2
SMAD6	0.026	0.004	-9999	-10000	0	0
CTDSP2	0.022	0.01	-9999	-10000	0	0
BMP2-4/FETUA	0.045	0.02	-9999	-0.043	1	1
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	0.021	0.01	-9999	-10000	0	0
BMPR2 (homodimer)	0.026	0	-9999	-10000	0	0
GADD34/PP1CA	0.049	0.015	-9999	-10000	0	0
BMPR1A-1B (homodimer)	0.027	0.018	-9999	0	44	44
CHRDL1	0.025	0.006	-9999	-10000	0	0
ENDOFIN/SMAD1	0.012	0.063	-9999	-0.24	2	2
SMAD6-7/SMURF1/SMAD1	0.021	0.057	-9999	-0.27	1	1
SMAD6/SMURF1	0.018	0.012	-9999	-10000	0	0
BAMBI	0.018	0.012	-9999	-10000	0	0
SMURF2	0.026	0.002	-9999	-10000	0	0
BMP2-4/CHRDL1	0.043	0.022	-9999	-0.043	1	1
BMP2-4/GREM1	0.038	0.025	-9999	-0.043	1	1
SMAD7	0.025	0.005	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.024	0.15	-9999	-0.42	17	17
SMAD1/SMAD6	0.007	0.049	-9999	-0.27	1	1
TAK1/SMAD6	0.026	0.018	-9999	0	50	50
BMP7	0.024	0.008	-9999	-10000	0	0
BMP6	0.025	0.005	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	0.009	0.046	-9999	-0.17	4	4
PPM1A	0.025	0.006	-9999	-10000	0	0
SMAD1/SMURF2	0.013	0.063	-9999	-0.24	2	2
SMAD7/SMURF1	0.026	0.018	-9999	0	50	50
CTDSPL	0.026	0.002	-9999	-10000	0	0
PPP1CA	0.026	0.002	-9999	-10000	0	0
XIAP	0.026	0.002	-9999	-10000	0	0
CTDSP1	0.026	0	-9999	-10000	0	0
PPP1R15A	0.025	0.006	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.012	0.053	-9999	-0.18	7	7
CHRD	0.026	0.004	-9999	-10000	0	0
BMPR2	0.026	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.015	0.051	-9999	-0.18	5	5
BMP4	0.024	0.009	-9999	-0.058	1	1
FST	0.011	0.032	-9999	-0.058	26	26
BMP2-4/NOG	0.046	0.02	-9999	-0.043	1	1
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	0.038	0.043	-9999	-10000	0	0

×

Glucocorticoid receptor regulatory network

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
PCK2	0.036	0.054	0.15	2	-0.26	1	3
SMARCC2	0.025	0.006	-10000	0	-10000	0	0
SMARCC1	0.026	0.002	-10000	0	-10000	0	0
TBX21	-0.015	0.021	-10000	0	-0.13	1	1
SUMO2	0.026	0.003	-10000	0	-10000	0	0
STAT1 (dimer)	0.028	0.008	-10000	0	-0.063	1	1
FKBP4	0.025	0.006	-10000	0	-10000	0	0
FKBP5	0.024	0.01	-10000	0	-0.058	2	2
GR alpha/HSP90/FKBP51/HSP90	0.085	0.052	0.18	15	-10000	0	15
PRL	-0.046	0.062	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/TIF2	0.025	0.088	0.26	3	-10000	0	3
RELA	0.018	0.031	-10000	0	-0.095	8	8
FGG	0.11	0.14	0.31	27	-10000	0	27
GR beta/TIF2	0.074	0.061	0.17	15	-10000	0	15
IFNG	-0.1	0.14	-10000	0	-0.34	26	26
apoptosis	0.021	0.067	-10000	0	-10000	0	0
CREB1	0.027	0.002	-10000	0	-10000	0	0
histone acetylation	-0.048	0.072	-10000	0	-0.18	15	15
BGLAP	-0.046	0.072	-10000	0	-0.22	2	2
GR/PKAc	0.089	0.057	0.18	15	-10000	0	15
NF kappa B1 p50/RelA	0.036	0.044	-10000	0	-0.14	8	8
SMARCD1	0.026	0.005	-10000	0	-10000	0	0
MDM2	0.042	0.053	0.13	21	-10000	0	21
GATA3	0.012	0.031	-10000	0	-10000	0	0
AKT1	0.023	0.006	-10000	0	-10000	0	0
CSF2	-0.066	0.078	-10000	0	-0.27	4	4
GSK3B	0.026	0.004	-10000	0	-10000	0	0
NR1I3	0.023	0.067	-10000	0	-10000	0	0
CSN2	0.098	0.13	0.29	26	-10000	0	26
BRG1/BAF155/BAF170/BAF60A	0.061	0.023	-10000	0	-10000	0	0
NFATC1	0.025	0.006	-10000	0	-10000	0	0
POU2F1	0.026	0.004	-10000	0	-10000	0	0
CDKN1A	-0.002	0.037	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
SFN	0.024	0.013	-10000	0	-0.058	3	3
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.094	0.056	0.18	16	-10000	0	16
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	0.019	0.072	-10000	0	-10000	0	0
JUN	-0.036	0.069	-10000	0	-0.24	4	4
IL4	-0.055	0.074	-10000	0	-0.19	16	16
CDK5R1	0.023	0.008	-10000	0	-10000	0	0
PRKACA	0.025	0.006	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.023	0.027	-10000	0	-10000	0	0
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.092	0.057	0.18	15	-10000	0	15
cortisol/GR alpha (monomer)	0.011	0.071	0.28	2	-10000	0	2
NCOA2	0.025	0.004	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.013	0.054	-10000	0	-0.089	46	46
AP-1/NFAT1-c-4	-0.1	0.13	0.2	1	-0.28	43	44
AFP	-0.098	0.099	-10000	0	-10000	0	0
SUV420H1	0.026	0.003	-10000	0	-10000	0	0
IRF1	0.081	0.086	0.22	18	-10000	0	18
TP53	0.03	0.008	-10000	0	-10000	0	0
PPP5C	0.025	0.006	-10000	0	-10000	0	0
KRT17	-0.18	0.26	-10000	0	-0.58	39	39
KRT14	-0.056	0.065	-10000	0	-10000	0	0
TBP	0.026	0.008	-10000	0	-10000	0	0
CREBBP	0.027	0.004	-10000	0	-10000	0	0
HDAC1	0.025	0.004	-10000	0	-10000	0	0
HDAC2	0.024	0.008	-10000	0	-10000	0	0
AP-1	-0.1	0.13	0.2	1	-0.28	43	44
MAPK14	0.026	0.004	-10000	0	-10000	0	0
MAPK10	0.026	0.003	-10000	0	-10000	0	0
MAPK11	0.023	0.008	-10000	0	-10000	0	0
KRT5	-0.14	0.22	-10000	0	-0.52	31	31
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
NCOA1	0.026	0.003	-10000	0	-10000	0	0
STAT1	0.028	0.008	-10000	0	-0.064	1	1
CGA	-0.053	0.074	-10000	0	-0.22	2	2
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.053	0.082	0.23	3	-10000	0	3
MAPK3	0.026	0.003	-10000	0	-10000	0	0
MAPK1	0.025	0.006	-10000	0	-10000	0	0
ICAM1	-0.058	0.084	-10000	0	-0.23	11	11
NFKB1	0.018	0.032	-10000	0	-0.095	8	8
MAPK8	-0.024	0.05	-10000	0	-0.18	5	5
MAPK9	0.026	0.003	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.02	0.067	-10000	0	-10000	0	0
BAX	-0.001	0.061	-10000	0	-0.36	2	2
POMC	-0.076	0.085	-10000	0	-10000	0	0
EP300	0.025	0.008	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/p53	0.032	0.091	0.29	3	-10000	0	3
proteasomal ubiquitin-dependent protein catabolic process	0.029	0.057	0.13	18	-10000	0	18
SGK1	0.003	0.085	-10000	0	-0.34	1	1
IL13	-0.084	0.14	-10000	0	-0.47	8	8
IL6	-0.037	0.074	-10000	0	-0.2	15	15
PRKACG	0.021	0.005	-10000	0	-10000	0	0
IL5	-0.11	0.14	-10000	0	-0.45	10	10
IL2	-0.1	0.14	-10000	0	-0.35	22	22
CDK5	0.018	0.012	-10000	0	-10000	0	0
PRKACB	0.025	0.005	-10000	0	-10000	0	0
HSP90AA1	0.024	0.007	-10000	0	-10000	0	0
IL8	-0.062	0.086	-10000	0	-0.2	23	23
CDK5R1/CDK5	0.023	0.019	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	0.058	0.054	-10000	0	-0.12	7	7
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.088	0.11	0.28	12	-10000	0	12
SMARCA4	0.025	0.006	-10000	0	-10000	0	0
chromatin remodeling	0.074	0.087	0.22	15	-0.2	1	16
NF kappa B1 p50/RelA/Cbp	0.055	0.053	-10000	0	-0.14	1	1
JUN (dimer)	-0.036	0.069	-10000	0	-0.24	4	4
YWHAH	0.024	0.007	-10000	0	-10000	0	0
VIPR1	-0.013	0.019	-10000	0	-10000	0	0
NR3C1	0.068	0.099	0.22	18	-10000	0	18
NR4A1	0.027	0.005	-10000	0	-10000	0	0
TIF2/SUV420H1	0.037	0.008	-10000	0	0	6	6
MAPKKK cascade	0.021	0.067	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/Src-1	0.027	0.088	0.26	3	-10000	0	3
PBX1	0.026	0.004	-10000	0	-10000	0	0
POU1F1	0.022	0.005	-10000	0	-10000	0	0
SELE	-0.065	0.12	-10000	0	-0.28	20	20
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.074	0.087	0.22	15	-0.21	1	16
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.088	0.11	0.28	12	-10000	0	12
mol:cortisol	0.024	0.059	0.17	11	-10000	0	11
MMP1	-0.007	0.034	-10000	0	-10000	0	0

×

Canonical Wnt signaling pathway

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
HDAC1	0.024	0.004	-10000	0	-10000	0	0
AES	0.024	0.005	-10000	0	-10000	0	0
FBXW11	0.026	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
LRP6/FZD1	0.025	0.019	-10000	0	0	53	53
SMAD4	0.025	0.005	-10000	0	-10000	0	0
DKK2	0.025	0.008	-10000	0	-0.058	1	1
TLE1	0.024	0.005	-10000	0	-10000	0	0
MACF1	0.026	0.004	-10000	0	-10000	0	0
CTNNB1	0.1	0.11	0.23	46	-0.52	1	47
WIF1	0.007	0.012	-10000	0	-0.02	3	3
beta catenin/RanBP3	0.048	0.065	-10000	0	-0.44	1	1
KREMEN2	0.025	0.008	-10000	0	-0.058	1	1
DKK1	0.004	0.031	0.057	1	-0.058	25	26
beta catenin/beta TrCP1	0.11	0.11	0.23	46	-0.48	1	47
FZD1	0.016	0.015	-10000	0	-0.059	2	2
AXIN2	-0.009	0.049	0.56	1	-10000	0	1
AXIN1	0.027	0.004	-10000	0	-10000	0	0
RAN	0.026	0.004	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.038	0.1	-10000	0	-0.68	2	2
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.065	0.075	0.24	9	-10000	0	9
Axin1/APC/GSK3	0.03	0.07	0.16	17	-0.29	2	19
Axin1/APC/GSK3/beta catenin/Macf1	0.065	0.1	0.2	35	-0.36	2	37
HNF1A	0.025	0.003	-10000	0	-10000	0	0
CTBP1	0.025	0	-10000	0	-10000	0	0
MYC	0.018	0.13	0.55	8	-10000	0	8
RANBP3	0.025	0.006	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.049	0.015	-10000	0	-10000	0	0
NKD1	0.024	0.007	-10000	0	-0.023	2	2
TCF4	0.024	0.005	-10000	0	-10000	0	0
TCF3	0.024	0.005	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0.042	0.034	-10000	0	-0.027	2	2
Ran/GTP	0.019	0.003	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.004	0.033	-10000	0	-10000	0	0
LEF1	0.024	0.01	-10000	0	-0.059	2	2
DVL1	0.016	0.035	-10000	0	-0.17	3	3
CSNK2A1	0.024	0.008	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.071	0.071	0.24	9	-10000	0	9
DKK1/LRP6/Kremen 2	0.039	0.029	-10000	0	-0.061	1	1
LRP6	0.026	0.006	-10000	0	-10000	0	0
CSNK1A1	0.026	0.004	-10000	0	-10000	0	0
NLK	0.026	0.003	-10000	0	-10000	0	0
CCND1	-0.013	0.015	-10000	0	-10000	0	0
WNT1	0.025	0.007	-10000	0	-0.02	1	1
GSK3A	0.026	0.006	-10000	0	-10000	0	0
GSK3B	0.026	0.004	-10000	0	-10000	0	0
FRAT1	0.018	0.012	-10000	0	-0.022	1	1
PPP2R5D	0.033	0.052	-10000	0	-0.24	3	3
APC	0.039	0.11	0.19	47	-10000	0	47
WNT1/LRP6/FZD1	0.001	0.033	-10000	0	-0.35	1	1
CREBBP	0.025	0.004	-10000	0	-10000	0	0

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	-0.004	0.038	0.14	4	-0.17	3	7
adherens junction organization	0.003	0.031	0.14	1	-10000	0	1
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.035	0.082	0.16	41	-10000	0	41
FMN1	0.001	0.031	0.13	1	-0.12	4	5
mol:IP3	-0.012	0.021	0.084	2	-0.11	2	4
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.014	0.032	0.14	1	-0.12	4	5
CTNNB1	0.026	0.003	-10000	0	-10000	0	0
AKT1	-0.006	0.036	0.093	13	-10000	0	13
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.018	0.049	0.16	1	-0.18	5	6
CTNND1	0.027	0.003	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.001	0.03	0.13	1	-0.12	3	4
VASP	-0.001	0.03	0.13	1	-0.12	4	5
ZYX	-0.001	0.026	0.13	1	-0.12	3	4
JUB	0.01	0.031	0.14	1	-0.12	4	5
EGFR(dimer)	0.008	0.028	0.15	1	-10000	0	1
E-cadherin/beta catenin-gamma catenin	0.05	0.012	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.04	0.045	0.15	13	-0.11	1	14
PIK3CA	0.025	0.009	-10000	0	-0.025	3	3
PI3K	0.041	0.046	0.15	13	-0.11	1	14
FYN	-0.019	0.055	0.13	3	-0.19	11	14
mol:Ca2+	-0.012	0.021	0.084	2	-0.11	2	4
JUP	0.026	0.007	-10000	0	-0.061	1	1
PIK3R1	0.026	0.007	-10000	0	-0.024	1	1
mol:DAG	-0.012	0.021	0.084	2	-0.11	2	4
CDH1	0.025	0.006	-10000	0	-10000	0	0
RhoA/GDP	0.074	0.093	0.16	76	-10000	0	76
establishment of polarity of embryonic epithelium	-0.001	0.03	0.13	1	-0.12	4	5
SRC	0.024	0.007	-10000	0	-10000	0	0
RAC1	0.017	0.012	-10000	0	-10000	0	0
RHOA	0.026	0.002	-10000	0	-10000	0	0
EGFR	0.007	0.016	-10000	0	-0.058	4	4
CASR	-0.014	0.028	0.13	3	-10000	0	3
RhoA/GTP	0.017	0.03	0.13	3	-10000	0	3
AKT2	-0.009	0.032	0.093	10	-10000	0	10
actin cable formation	-0.005	0.033	0.14	2	-0.13	1	3
apoptosis	-0.01	0.037	0.13	1	-0.15	4	5
CTNNA1	0.026	0.004	-10000	0	-10000	0	0
mol:GDP	-0.009	0.018	-10000	0	-0.12	2	2
PIP5K1A	0.001	0.03	0.13	1	-0.12	3	4
PLCG1	-0.012	0.021	0.085	2	-0.11	2	4
Rac1/GTP	0.01	0.03	-10000	0	-10000	0	0
homophilic cell adhesion	0	0.003	-10000	0	-10000	0	0

×

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

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
MAP4K1	-0.002	0.076	0.19	8	-0.32	5	13
CRKL	-0.005	0.066	0.19	1	-0.33	5	6
HRAS	0.004	0.078	0.16	1	-0.31	5	6
mol:PIP3	0.061	0.11	0.25	11	-0.31	5	16
SPRED1	0.025	0.005	-10000	0	-10000	0	0
SPRED2	0.026	0.004	-10000	0	-10000	0	0
GAB1	0.003	0.067	-10000	0	-0.34	5	5
FOXO3	0.048	0.13	0.24	10	-0.34	8	18
AKT1	0.053	0.13	0.23	12	-0.35	8	20
BAD	0.046	0.13	0.23	7	-0.34	8	15
megakaryocyte differentiation	0.003	0.065	-10000	0	-0.33	5	5
GSK3B	0.048	0.13	0.24	11	-0.34	8	19
RAF1	-0.009	0.068	0.14	2	-0.27	5	7
SHC1	0.023	0.013	-10000	0	-0.058	3	3
STAT3	0.001	0.067	-10000	0	-0.34	5	5
STAT1	-0.006	0.13	-10000	0	-0.71	4	4
HRAS/SPRED1	0.01	0.075	-10000	0	-0.27	5	5
cell proliferation	-0.004	0.063	-10000	0	-0.33	5	5
PIK3CA	0.026	0.004	-10000	0	-10000	0	0
TEC	0.024	0.009	-10000	0	-0.058	1	1
RPS6KB1	0.034	0.09	-10000	0	-0.36	4	4
HRAS/SPRED2	0.012	0.076	-10000	0	-0.27	5	5
LYN/TEC/p62DOK	0.039	0.081	-10000	0	-0.33	5	5
MAPK3	-0.006	0.065	0.18	7	-0.2	5	12
STAP1	0	0.067	-10000	0	-0.34	5	5
GRAP2	0.022	0.012	-10000	0	-0.058	2	2
JAK2	-0.011	0.12	-10000	0	-0.61	4	4
STAT1 (dimer)	-0.007	0.13	-10000	0	-0.69	4	4
mol:Gleevec	-0.001	0.004	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	0.044	0.086	-10000	0	-0.33	5	5
actin filament polymerization	-0.005	0.057	-10000	0	-0.33	4	4
LYN	0.026	0.004	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.007	0.09	-10000	0	-0.43	5	5
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
CBL/CRKL/GRB2	0.019	0.073	0.2	1	-0.31	5	6
PI3K	0.058	0.097	-10000	0	-0.32	5	5
PTEN	0.016	0.013	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	0.01	0.14	-10000	0	-0.78	4	4
MAPK8	-0.004	0.064	-10000	0	-0.34	5	5
STAT3 (dimer)	0.001	0.066	-10000	0	-0.33	5	5
positive regulation of transcription	-0.003	0.057	0.16	7	-0.16	5	12
mol:GDP	0.01	0.073	-10000	0	-0.31	5	5
PIK3C2B	-0.001	0.066	-10000	0	-0.34	5	5
CBL/CRKL	0.01	0.072	0.2	2	-0.32	5	7
FER	0.002	0.066	-10000	0	-0.34	5	5
SH2B3	0.001	0.067	-10000	0	-0.34	5	5
PDPK1	0.056	0.099	0.24	10	-0.3	4	14
SNAI2	0.001	0.066	-10000	0	-0.34	5	5
positive regulation of cell proliferation	-0.006	0.11	-10000	0	-0.56	4	4
KITLG	0.023	0.017	-10000	0	-0.047	4	4
cell motility	-0.006	0.11	-10000	0	-0.56	4	4
PTPN6	0.022	0.012	-10000	0	-0.023	7	7
EPOR	0.019	0.064	-10000	0	-0.52	1	1
STAT5A (dimer)	0.002	0.094	-10000	0	-0.47	4	4
SOCS1	-0.023	0.041	-10000	0	-0.058	84	84
cell migration	0.003	0.06	0.31	5	-10000	0	5
SOS1	0.026	0	-10000	0	-10000	0	0
EPO	0.011	0.027	-10000	0	-0.055	14	14
VAV1	0.025	0.005	-10000	0	-10000	0	0
GRB10	-0.006	0.058	-10000	0	-0.33	4	4
PTPN11	0.02	0.016	-10000	0	-0.026	14	14
SCF/KIT	0.008	0.07	-10000	0	-0.34	5	5
GO:0007205	0	0.004	-10000	0	-10000	0	0
MAP2K1	-0.015	0.058	0.14	2	-0.22	5	7
CBL	0.026	0.002	-10000	0	-10000	0	0
KIT	-0.004	0.15	-10000	0	-0.72	6	6
MAP2K2	-0.008	0.075	0.23	7	-0.22	5	12
SHC/Grb2/SOS1	0.039	0.081	-10000	0	-0.33	5	5
STAT5A	0.001	0.096	-10000	0	-0.48	4	4
GRB2	0.025	0.004	-10000	0	-10000	0	0
response to radiation	0.001	0.065	-10000	0	-0.33	5	5
SHC/GRAP2	0.035	0.014	0.082	1	0	18	19
PTPRO	0.003	0.066	-10000	0	-0.34	5	5
SH2B2	-0.006	0.058	-10000	0	-0.33	4	4
DOK1	0.026	0	-10000	0	-10000	0	0
MATK	-0.003	0.061	-10000	0	-0.32	5	5
CREBBP	0.027	0.024	-10000	0	-0.11	4	4
BCL2	0.011	0.09	-10000	0	-0.64	1	1

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.036	0.012	-10000	0	0	13	13
ATM	0.026	0.002	-10000	0	-10000	0	0
UBE2D3	0.026	0.002	-10000	0	-10000	0	0
PRKDC	0.026	0.004	-10000	0	-10000	0	0
ATR	0.026	0.004	-10000	0	-10000	0	0
UBE2L3	0.025	0.006	-10000	0	-10000	0	0
FANCD2	0.013	0.003	-10000	0	-10000	0	0
protein ubiquitination	0.069	0.03	-10000	0	-0.048	1	1
XRCC5	0.026	0	-10000	0	-10000	0	0
XRCC6	0.024	0.007	-10000	0	-10000	0	0
M/R/N Complex	0.051	0.011	-10000	0	-10000	0	0
MRE11A	0.026	0.003	-10000	0	-10000	0	0
DNA-PK	0.047	0.017	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	-0.008	0.084	-10000	0	-0.52	2	2
FANCF	0.026	0.003	-10000	0	-10000	0	0
BRCA1	0.025	0.007	-10000	0	-0.058	1	1
CCNE1	0.024	0.007	-10000	0	-10000	0	0
CDK2/Cyclin E1	0.045	0.018	-10000	0	0	15	15
FANCG	0.024	0.008	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.039	0.006	0.082	1	0	1	2
FANCE	0.026	0.003	-10000	0	-10000	0	0
FANCC	0.023	0.014	-10000	0	-0.058	4	4
NBN	0.025	0.004	-10000	0	-10000	0	0
FANCA	0.025	0.006	-10000	0	-10000	0	0
DNA repair	-0.029	0.07	0.16	4	-0.35	2	6
BRCA1/BARD1/ubiquitin	0.039	0.006	0.082	1	0	1	2
BARD1/DNA-PK	0.058	0.029	-10000	0	-0.028	14	14
FANCL	0.026	0.002	-10000	0	-10000	0	0
mRNA polyadenylation	-0.036	0.012	0	13	-10000	0	13
BRCA1/BARD1/CTIP/M/R/N Complex	0.012	0.019	0.11	3	-10000	0	3
BRCA1/BACH1/BARD1/TopBP1	0.053	0.009	0.092	1	-10000	0	1
BRCA1/BARD1/P53	0.063	0.023	-10000	0	-0.028	7	7
BARD1/CSTF1/BRCA1	0.049	0.016	0.092	1	-10000	0	1
BRCA1/BACH1	0.025	0.007	-10000	0	-0.058	1	1
BARD1	0.024	0.014	-10000	0	-0.058	4	4
PCNA	0.021	0.017	-10000	0	-0.058	5	5
BRCA1/BARD1/UbcH5C	0.053	0.008	0.092	1	-10000	0	1
BRCA1/BARD1/UbcH7	0.051	0.013	0.092	1	-10000	0	1
BRCA1/BARD1/RAD51/PCNA	0.072	0.032	0.12	1	-0.049	4	5
BARD1/DNA-PK/P53	0.063	0.039	-10000	0	-0.049	3	3
BRCA1/BARD1/Ubiquitin	0.039	0.006	0.082	1	0	1	2
BRCA1/BARD1/CTIP	0.035	0.016	0.077	1	-0.048	3	4
FA complex	0.009	0.035	-10000	0	-0.2	3	3
BARD1/EWS	0.037	0.01	-10000	0	0	8	8
RBBP8	-0.021	0.006	0	6	-0.047	3	9
TP53	0.022	0.017	-10000	0	-0.058	6	6
TOPBP1	0.026	0.003	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.061	0.022	0.028	7	-10000	0	7
BRCA1/BARD1	0.076	0.033	-10000	0	-0.049	1	1
CSTF1	0.024	0.007	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.02	0.003	0.041	4	-10000	0	4
CDK2	-0.017	0.041	-10000	0	-0.058	73	73
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.036	0.036	-10000	0	-0.058	107	107
RAD50	0.026	0.003	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.039	0.006	0.082	1	0	1	2
EWSR1	0.025	0.006	-10000	0	-10000	0	0

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.026	0	-10000	0	-10000	0	0
ANTXR2	0.018	0.025	-10000	0	-0.058	14	14
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.004	0.001	-10000	0	-0.007	14	14
monocyte activation	0.009	0.059	-10000	0	-0.31	5	5
MAP2K2	0.009	0.048	-10000	0	-0.57	1	1
MAP2K1	-0.01	0.002	0	3	-10000	0	3
MAP2K7	-0.01	0.002	0	6	-10000	0	6
MAP2K6	-0.01	0.001	0	1	-10000	0	1
CYAA	-0.015	0.005	0	1	-0.03	14	15
MAP2K4	-0.01	0.001	0	1	-10000	0	1
IL1B	-0.01	0.002	-10000	0	-10000	0	0
Channel	0.035	0.006	-10000	0	0	1	1
NLRP1	-0.01	0.002	0	3	-10000	0	3
CALM1	0.024	0.007	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.022	0.11	-10000	0	-0.4	11	11
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.004	0.001	0.007	14	-10000	0	14
MAPK3	-0.01	0.002	0	2	-10000	0	2
MAPK1	-0.01	0.002	0	7	-10000	0	7
PGR	-0.01	0.002	0	6	-10000	0	6
PA/Cellular Receptors	0.037	0.006	-10000	0	0	1	1
apoptosis	-0.004	0.001	-10000	0	-0.007	14	14
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.034	0.007	-10000	0	-0.025	1	1
macrophage activation	-0.016	0.004	-10000	0	-10000	0	0
TNF	0.025	0.005	-10000	0	-10000	0	0
VCAM1	0.009	0.06	-10000	0	-0.31	5	5
platelet activation	-0.022	0.11	-10000	0	-0.4	11	11
MAPKKK cascade	0.007	0.017	0.058	1	-0.068	7	8
IL18	-0.01	0.003	-10000	0	-10000	0	0
negative regulation of macrophage activation	-0.004	0.001	-10000	0	-0.007	14	14
LEF	-0.004	0.001	-10000	0	-0.007	14	14
CASP1	-0.004	0.002	-10000	0	-0.011	1	1
mol:cAMP	-0.023	0.11	-10000	0	-0.4	11	11
necrosis	-0.004	0.001	-10000	0	-0.007	14	14
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.034	0.006	-10000	0	0	1	1
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.025	0.008	-10000	0	-0.058	1	1
Jak2/Leptin Receptor	0.007	0.12	-10000	0	-0.28	18	18
PTP1B/AKT1	0.046	0.042	0.16	3	-10000	0	3
FYN	0.024	0.007	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	0.038	0.045	0.16	4	-10000	0	4
EGFR	0.007	0.017	-10000	0	-0.052	5	5
EGF/EGFR	0.013	0.027	-10000	0	-10000	0	0
CSF1	0.026	0.003	-10000	0	-10000	0	0
AKT1	0.024	0.009	-10000	0	-0.022	2	2
INSR	0.024	0.009	-10000	0	-0.023	4	4
PTP1B/N-cadherin	0.047	0.042	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.05	0.043	0.17	1	-10000	0	1
HCK	0.023	0.01	-10000	0	-0.058	1	1
CRK	0.026	0.004	-10000	0	-10000	0	0
TYK2	0.038	0.067	0.27	8	-10000	0	8
EGF	0.03	0.004	-10000	0	-10000	0	0
YES1	0.025	0.005	-10000	0	-10000	0	0
CAV1	0.075	0.071	0.17	40	-10000	0	40
TXN	0.027	0.007	-10000	0	-0.023	1	1
PTP1B/IRS1/GRB2	0.061	0.047	0.21	1	-10000	0	1
cell migration	-0.038	0.045	-10000	0	-0.16	4	4
STAT3	0.027	0.001	-10000	0	-10000	0	0
PRLR	0.025	0.006	-10000	0	-10000	0	0
ITGA2B	0.026	0.003	-10000	0	-10000	0	0
CSF1R	0.026	0.003	-10000	0	-10000	0	0
Prolactin Receptor/Prolactin	0.033	0.01	-10000	0	-10000	0	0
FGR	0.025	0.005	-10000	0	-10000	0	0
PTP1B/p130 Cas	0.045	0.044	0.21	1	-10000	0	1
Crk/p130 Cas	0.057	0.047	0.21	1	-10000	0	1
DOK1	0.03	0.05	0.17	3	-0.22	2	5
JAK2	-0.004	0.12	0.21	1	-0.29	18	19
Jak2/Leptin Receptor/Leptin	0.027	0.062	-10000	0	-0.23	2	2
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
PTPN1	0.038	0.045	0.16	4	-10000	0	4
LYN	0.026	0.004	-10000	0	-10000	0	0
CDH2	0.025	0.005	-10000	0	-10000	0	0
SRC	0.035	0.037	-10000	0	-0.27	1	1
ITGB3	0	0.04	0.058	3	-0.058	47	50
CAT1/PTP1B	0.049	0.081	0.22	16	-10000	0	16
CAPN1	0.026	0.003	-10000	0	-10000	0	0
CSK	0.025	0.004	-10000	0	-10000	0	0
PI3K	0.05	0.05	-10000	0	-10000	0	0
mol:H2O2	0.003	0.004	-10000	0	-10000	0	0
STAT3 (dimer)	0.025	0.057	-10000	0	-0.21	2	2
negative regulation of transcription	-0.004	0.12	0.21	1	-0.29	18	19
FCGR2A	0.014	0.03	-10000	0	-0.058	21	21
FER	0.028	0.005	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	0.046	0.011	0.067	1	0	2	3
BLK	0.021	0.014	-10000	0	-0.058	4	4
Insulin Receptor/Insulin/Shc	0.044	0.016	-10000	0	-10000	0	0
RHOA	0.026	0.003	-10000	0	-10000	0	0
LEPR	0.025	0.005	-10000	0	-10000	0	0
BCAR1	0.025	0.005	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.025	0.004	-10000	0	-10000	0	0
mol:NADPH	0.002	0.002	-10000	0	-10000	0	0
TRPV6	0.026	0.072	0.22	5	-0.21	1	6
PRL	0.02	0.009	-10000	0	-0.059	1	1
SOCS3	0.019	0.014	-10000	0	-10000	0	0
SPRY2	0.028	0.007	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.045	0.014	-10000	0	-10000	0	0
CSF1/CSF1R	0.061	0.043	-10000	0	-10000	0	0
Ras protein signal transduction	-0.012	0.094	0.54	4	-10000	0	4
IRS1	0.026	0	-10000	0	-10000	0	0
INS	0.018	0.01	-10000	0	-0.022	8	8
LEP	0.015	0.015	-10000	0	-0.026	7	7
STAT5B	0.026	0.062	0.23	1	-0.2	2	3
STAT5A	0.026	0.062	0.23	1	-0.2	2	3
GRB2	0.025	0.004	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.051	0.041	0.21	1	-10000	0	1
CSN2	-0.01	0.029	-10000	0	-10000	0	0
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
LAT	0.036	0.046	-10000	0	-0.31	2	2
YBX1	0.03	0.006	-10000	0	-10000	0	0
LCK	0.002	0.037	-10000	0	-0.058	40	40
SHC1	0.023	0.013	-10000	0	-0.058	3	3
NOX4	0.024	0.053	0.062	91	-0.059	42	133

×

Arf6 downstream 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
PLAUR	0.001	0.025	-10000	0	-10000	0	0
regulation of axonogenesis	0.016	0.054	0.26	7	-10000	0	7
myoblast fusion	-0.017	0.015	-10000	0	-10000	0	0
mol:GTP	0.01	0.046	-10000	0	-0.17	9	9
regulation of calcium-dependent cell-cell adhesion	-0.038	0.04	0.11	9	-10000	0	9
ARF1/GTP	0.025	0.041	-10000	0	-0.13	9	9
mol:GM1	-0.001	0.032	-10000	0	-0.12	9	9
mol:Choline	-0.019	0.024	-10000	0	-0.12	7	7
lamellipodium assembly	-0.005	0.067	-10000	0	-0.36	5	5
MAPK3	0.004	0.031	-10000	0	-0.11	9	9
ARF6/GTP/NME1/Tiam1	0.039	0.041	-10000	0	-0.11	9	9
ARF1	0.025	0.005	-10000	0	-10000	0	0
ARF6/GDP	0.017	0.015	-10000	0	-10000	0	0
ARF1/GDP	0.009	0.061	-10000	0	-0.22	9	9
ARF6	0.032	0.009	-10000	0	-10000	0	0
RAB11A	0.025	0.004	-10000	0	-10000	0	0
TIAM1	0.024	0.011	-10000	0	-0.041	1	1
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.006	0.028	-10000	0	-0.11	7	7
actin filament bundle formation	-0.015	0.06	0.22	8	-10000	0	8
KALRN	0.002	0.037	-10000	0	-0.24	3	3
RAB11FIP3/RAB11A	0.037	0.008	-10000	0	0	6	6
RhoA/GDP	0.015	0.06	-10000	0	-0.23	8	8
NME1	0.024	0.011	-10000	0	-0.043	2	2
Rac1/GDP	0.009	0.049	-10000	0	-0.21	6	6
substrate adhesion-dependent cell spreading	0.01	0.046	-10000	0	-0.17	9	9
cortical actin cytoskeleton organization	-0.005	0.067	-10000	0	-0.36	5	5
RAC1	0.017	0.012	-10000	0	-10000	0	0
liver development	0.01	0.046	-10000	0	-0.17	9	9
ARF6/GTP	0.01	0.046	-10000	0	-0.17	9	9
RhoA/GTP	0.027	0.039	-10000	0	-0.14	8	8
mol:GDP	-0.006	0.057	-10000	0	-0.24	8	8
ARF6/GTP/RAB11FIP3/RAB11A	0.039	0.042	-10000	0	-0.12	9	9
RHOA	0.026	0.002	-10000	0	-10000	0	0
PLD1	0.006	0.034	-10000	0	-0.14	8	8
RAB11FIP3	0.026	0.004	-10000	0	-10000	0	0
tube morphogenesis	-0.005	0.067	-10000	0	-0.36	5	5
ruffle organization	-0.016	0.054	-10000	0	-0.26	7	7
regulation of epithelial cell migration	0.01	0.046	-10000	0	-0.17	9	9
PLD2	0.006	0.034	-10000	0	-0.13	8	8
PIP5K1A	-0.016	0.055	-10000	0	-0.26	7	7
mol:Phosphatidic acid	-0.019	0.024	-10000	0	-0.12	7	7
Rac1/GTP	-0.005	0.067	-10000	0	-0.36	5	5

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	0.051	0.01	-10000	0	-10000	0	0
fibroblast growth factor receptor signaling pathway	0.051	0.01	-10000	0	-10000	0	0
LAMA1	0.024	0.011	-10000	0	-0.058	2	2
PRNP	0.024	0.008	-10000	0	-10000	0	0
GPC1/SLIT2	0.026	0.018	-10000	0	0	49	49
SMAD2	-0.026	0.024	0.17	2	-10000	0	2
GPC1/PrPc/Cu2+	0.032	0.011	-10000	0	0	15	15
GPC1/Laminin alpha1	0.037	0.009	-10000	0	0	7	7
TDGF1	0.025	0.003	-10000	0	-10000	0	0
CRIPTO/GPC1	0.038	0.005	-10000	0	0	2	2
APP/GPC1	0.038	0.006	-10000	0	0	4	4
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.025	0.006	-10000	0	-10000	0	0
FLT1	0.024	0.007	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	0.051	0.011	-10000	0	-10000	0	0
SERPINC1	0.021	0.019	-10000	0	-0.058	8	8
FYN	-0.023	0.008	-10000	0	-10000	0	0
FGR	-0.025	0.006	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	0.003	0.061	0.18	13	-10000	0	13
SLIT2	0.018	0.012	-10000	0	-10000	0	0
GPC1/NRG	0.033	0.014	-10000	0	0	22	22
NRG1	0.022	0.009	-10000	0	-10000	0	0
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.049	0.027	-10000	0	-0.046	6	6
LYN	-0.025	0.005	-10000	0	-10000	0	0
mol:Spermine	-0.011	0.001	-10000	0	-10000	0	0
cell growth	0.051	0.01	-10000	0	-10000	0	0
BMP signaling pathway	-0.026	0.002	-10000	0	-10000	0	0
SRC	-0.024	0.007	-10000	0	-10000	0	0
TGFBR1	0.025	0.004	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.015	0.042	-10000	0	-0.058	71	71
GPC1	0.026	0.002	-10000	0	-10000	0	0
TGFBR1 (dimer)	0.025	0.004	-10000	0	-10000	0	0
VEGFA	0.002	0.038	-10000	0	-0.058	41	41
BLK	-0.026	0.006	-10000	0	-10000	0	0
HCK	-0.023	0.008	-10000	0	-10000	0	0
FGF2	0.026	0.002	-10000	0	-10000	0	0
FGFR1	0.025	0.004	-10000	0	-10000	0	0
VEGFR1 homodimer	0.024	0.007	-10000	0	-10000	0	0
TGFBR2	0.026	0.002	-10000	0	-10000	0	0
cell death	0.038	0.006	-10000	0	0	4	4
ATIII/GPC1	0.039	0.008	-10000	0	0	3	3
PLA2G2A/GPC1	0.048	0.014	-10000	0	0	5	5
LCK	-0.03	0.011	-10000	0	-10000	0	0
neuron differentiation	0.033	0.014	-10000	0	0	22	22
PrPc/Cu2+	0.018	0.006	-10000	0	-10000	0	0
APP	0.026	0.004	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.026	0.002	-10000	0	-10000	0	0

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.025	0.004	-10000	0	-10000	0	0
LAT2	-0.003	0.027	0.15	3	-0.16	1	4
AP1	-0.019	0.12	-10000	0	-0.28	4	4
mol:PIP3	0.044	0.094	0.26	12	-10000	0	12
IKBKB	0.006	0.074	0.2	10	-10000	0	10
AKT1	-0.04	0.073	0.31	4	-10000	0	4
IKBKG	0.007	0.07	0.19	10	-10000	0	10
MS4A2	-0.009	0.021	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
MAP3K1	0.002	0.056	0.25	3	-0.2	2	5
mol:Ca2+	0.041	0.084	0.23	13	-10000	0	13
LYN	0.025	0.007	-10000	0	-0.027	1	1
CBLB	-0.004	0.028	0.11	3	-0.14	2	5
SHC1	0.023	0.013	-10000	0	-0.058	3	3
RasGAP/p62DOK	0.049	0.011	-10000	0	-0.019	3	3
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	0.026	0	-10000	0	-10000	0	0
PLD2	-0.034	0.059	0.43	2	-10000	0	2
PTPN13	0.02	0.06	-10000	0	-0.55	1	1
PTPN11	0.025	0.01	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	-0.005	0.073	0.31	5	-0.28	1	6
SYK	0.024	0.009	-10000	0	-0.061	1	1
GRB2	0.026	0.004	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	0.049	0.043	0.16	8	-10000	0	8
LAT	-0.004	0.028	0.11	3	-0.14	2	5
PAK2	0.007	0.054	0.18	5	-0.22	2	7
NFATC2	-0.001	0.009	-10000	0	-10000	0	0
HRAS	0.011	0.054	0.19	4	-0.22	2	6
GAB2	0.026	0.002	-10000	0	-10000	0	0
PLA2G1B	0.02	0.04	-10000	0	-10000	0	0
Fc epsilon R1	0.06	0.017	0.097	3	-10000	0	3
Antigen/IgE/Fc epsilon R1	0.058	0.016	0.097	3	-10000	0	3
mol:GDP	0.02	0.046	0.17	7	-10000	0	7
JUN	0.025	0.004	-10000	0	-10000	0	0
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
FOS	0.024	0.008	-10000	0	-10000	0	0
Antigen/IgE/Fc epsilon R1/LYN/SYK	0.013	0.027	0.12	3	-0.16	1	4
CHUK	0	0.061	0.18	9	-10000	0	9
KLRG1	-0.005	0.019	0.084	1	-10000	0	1
VAV1	-0.005	0.029	0.11	3	-0.16	1	4
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.004	0.028	0.11	3	-0.14	2	5
negative regulation of mast cell degranulation	0.01	0.049	0.19	6	-0.18	1	7
BTK	0.018	0.031	-10000	0	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	0.015	0.013	0.11	1	-10000	0	1
GAB2/PI3K/SHP2	-0.054	0.019	-10000	0	-10000	0	0
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	0.007	0.014	-10000	0	-10000	0	0
RAF1	0.023	0.012	-10000	0	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	0.095	0.021	-10000	0	-10000	0	0
FCER1G	0.013	0.032	-10000	0	-0.062	22	22
FCER1A	-0.003	0.042	0.069	4	-0.058	51	55
Antigen/IgE/Fc epsilon R1/Fyn	0.062	0.03	-10000	0	-0.036	3	3
MAPK3	0.021	0.036	-10000	0	-10000	0	0
MAPK1	0.016	0.045	-10000	0	-10000	0	0
NFKB1	0.026	0.002	-10000	0	-10000	0	0
MAPK8	-0.12	0.25	-10000	0	-0.5	44	44
DUSP1	0.025	0.008	-10000	0	-0.058	1	1
NF-kappa-B/RelA	-0.001	0.047	0.11	8	-10000	0	8
actin cytoskeleton reorganization	0.027	0.062	-10000	0	-0.56	1	1
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	0.031	0.051	0.18	6	-0.19	2	8
FER	-0.004	0.028	0.11	3	-0.14	2	5
RELA	0.026	0.003	-10000	0	-10000	0	0
ITK	0.005	0.019	-10000	0	-0.21	1	1
SOS1	0.026	0	-10000	0	-10000	0	0
PLCG1	0.035	0.073	0.25	10	-10000	0	10
cytokine secretion	-0.005	0.029	0.062	5	-10000	0	5
SPHK1	-0.005	0.028	0.11	3	-0.14	2	5
PTK2	0.027	0.064	-10000	0	-0.59	1	1
NTAL/PLCgamma1/GRB2/SLP76/GADs	0.047	0.055	0.18	15	-10000	0	15
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	0.038	0.086	0.24	12	-10000	0	12
MAP2K2	0.021	0.049	-10000	0	-10000	0	0
MAP2K1	0.013	0.022	-10000	0	-10000	0	0
MAP2K7	0.025	0.005	-10000	0	-10000	0	0
KLRG1/SHP2	0.004	0.039	0.18	3	-0.19	1	4
MAP2K4	0.029	0.071	-10000	0	-0.82	1	1
Fc epsilon R1/FcgammaRIIB	0.086	0.021	0.12	12	-10000	0	12
mol:Choline	-0.034	0.058	0.43	2	-10000	0	2
SHC/Grb2/SOS1	0.056	0.038	0.18	2	-0.15	1	3
FYN	0.024	0.007	-10000	0	-10000	0	0
DOK1	0.026	0	-10000	0	-10000	0	0
PXN	0.023	0.069	0.34	2	-0.55	1	3
HCLS1	-0.004	0.028	0.11	3	-0.14	2	5
PRKCB	0.008	0.079	0.21	9	-10000	0	9
FCGR2B	-0.029	0.04	-10000	0	-0.058	95	95
IGHE	-0.001	0.004	-10000	0	-10000	0	0
KLRG1/SHIP	0.011	0.049	0.2	6	-0.18	1	7
LCP2	0.025	0.008	-10000	0	-0.058	1	1
PLA2G4A	-0.004	0.028	0.11	3	-0.14	2	5
RASA1	0.026	0.004	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.034	0.058	0.43	2	-10000	0	2
IKK complex	0.003	0.067	0.2	9	-10000	0	9
WIPF1	0.026	0	-10000	0	-10000	0	0

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	-0.033	0.13	-10000	0	-0.24	27	27
CaM/Ca2+	0.018	0.005	-10000	0	0	11	11
AKT1	0.024	0.007	-10000	0	-10000	0	0
AKT2	0.025	0.006	-10000	0	-10000	0	0
STXBP4	0.026	0.002	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	-0.05	0.13	-10000	0	-0.26	26	26
YWHAZ	0.025	0.005	-10000	0	-10000	0	0
CALM1	0.024	0.007	-10000	0	-10000	0	0
YWHAQ	0.026	0.002	-10000	0	-10000	0	0
TBC1D4	-0.02	0.007	0	15	-10000	0	15
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.024	0.007	-10000	0	-10000	0	0
YWHAB	0.024	0.007	-10000	0	-10000	0	0
SNARE/Synip	0.051	0.01	-10000	0	-10000	0	0
YWHAG	0.018	0.012	-10000	0	-10000	0	0
ASIP	-0.004	0.039	-10000	0	-0.058	49	49
PRKCI	0.026	0.003	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0.018	0.005	-10000	0	0	11	11
RHOQ	0.026	0	-10000	0	-10000	0	0
GYS1	-0.007	0.003	-10000	0	-10000	0	0
PRKCZ	0.019	0.011	-10000	0	-10000	0	0
TRIP10	0.025	0.005	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.034	0.007	-10000	0	0	6	6
AS160/14-3-3	0.001	0.03	0.11	1	-0.15	2	3
VAMP2	0.026	0.004	-10000	0	-10000	0	0
SLC2A4	-0.056	0.14	-10000	0	-0.28	26	26
STX4	0.026	0.003	-10000	0	-10000	0	0
GSK3B	0.012	0.004	-10000	0	-10000	0	0
SFN	0.024	0.013	-10000	0	-0.058	3	3
LNPEP	0.025	0.004	-10000	0	-10000	0	0
YWHAE	0.026	0.004	-10000	0	-10000	0	0

×

mTOR signaling pathway

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
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.025	0.004	-10000	0	-10000	0	0
mol:PIP3	-0.007	0.012	-10000	0	-10000	0	0
FRAP1	0.045	0.054	0.27	1	-10000	0	1
AKT1	0.042	0.087	0.16	49	-0.13	1	50
INSR	0.025	0.005	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.029	0.009	-10000	0	0	13	13
mol:GTP	0.041	0.088	0.16	47	-10000	0	47
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.009	0.016	-10000	0	-10000	0	0
TSC2	0.026	0.004	-10000	0	-10000	0	0
RHEB/GDP	-0.006	0.039	0.095	15	-0.13	1	16
TSC1	0.025	0.006	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.025	0.007	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.039	0.038	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.018	0.012	-10000	0	-10000	0	0
RPS6KB1	0.055	0.072	0.21	9	-10000	0	9
MAP3K5	-0.018	0.065	0.18	2	-0.2	15	17
PIK3R1	0.026	0.005	-10000	0	-10000	0	0
apoptosis	-0.018	0.065	0.18	2	-0.2	15	17
mol:LY294002	0	0	-10000	0	-10000	0	0
EIF4B	0.049	0.071	0.2	11	-10000	0	11
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.028	0.042	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	0.016	0.021	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.044	0.017	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.016	0.06	0.13	24	-10000	0	24
FKBP1A	0.024	0.007	-10000	0	-10000	0	0
RHEB/GTP	0.002	0.056	0.14	17	-10000	0	17
mol:Amino Acids	0	0	-10000	0	-10000	0	0
FKBP12/Rapamycin	0.019	0.006	-10000	0	0	12	12
PDPK1	-0.01	0.023	0.16	2	-10000	0	2
EIF4E	0.026	0.002	-10000	0	-10000	0	0
ASK1/PP5C	-0.008	0.18	-10000	0	-0.52	15	15
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.014	0.032	-10000	0	-0.24	1	1
TSC1/TSC2	0.045	0.095	0.17	47	-10000	0	47
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RPS6	0.022	0.011	-10000	0	-0.058	1	1
PPP5C	0.025	0.006	-10000	0	-10000	0	0
EIF4G1	0.026	0.004	-10000	0	-10000	0	0
IRS1	0.009	0.005	-10000	0	-10000	0	0
INS	0.019	0.004	-10000	0	-10000	0	0
PTEN	0.016	0.013	-10000	0	-10000	0	0
PDK2	-0.01	0.023	0.16	2	-10000	0	2
EIF4EBP1	0.028	0.087	-10000	0	-1	1	1
PIK3CA	0.026	0.004	-10000	0	-10000	0	0
PPP2R5D	0.037	0.052	0.25	1	-10000	0	1
peptide biosynthetic process	-0.022	0.005	-10000	0	-10000	0	0
RHEB	0.018	0.012	-10000	0	-10000	0	0
EIF4A1	0.025	0.004	-10000	0	-10000	0	0
mol:Rapamycin	0.001	0.001	0.004	7	-10000	0	7
EEF2	-0.022	0.005	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.039	0.082	-10000	0	-0.94	1	1

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.023	0.019	-10000	0	0	58	58
VLDLR	0.023	0.009	-10000	0	-10000	0	0
CRKL	0.025	0.006	-10000	0	-10000	0	0
LRPAP1	0.026	0	-10000	0	-10000	0	0
FYN	0.024	0.007	-10000	0	-10000	0	0
ITGA3	0.024	0.012	-10000	0	-0.058	3	3
RELN/VLDLR/Fyn	0.012	0.022	-10000	0	-10000	0	0
MAPK8IP1/MKK7/MAP3K11/JNK1	0.044	0.049	-10000	0	-10000	0	0
AKT1	-0.049	0.057	-10000	0	-0.17	14	14
MAP2K7	0.025	0.005	-10000	0	-10000	0	0
RAPGEF1	0.025	0.006	-10000	0	-10000	0	0
DAB1	0.019	0.012	-10000	0	-10000	0	0
RELN/LRP8/DAB1	0.009	0.02	-10000	0	-0.02	1	1
LRPAP1/LRP8	0.037	0.008	-10000	0	0	6	6
RELN/LRP8/DAB1/Fyn	0.007	0.027	-10000	0	-10000	0	0
DAB1/alpha3/beta1 Integrin	-0.005	0.032	-10000	0	-10000	0	0
long-term memory	0.001	0.017	-10000	0	-10000	0	0
DAB1/LIS1	0.001	0.035	-10000	0	-10000	0	0
DAB1/CRLK/C3G	-0.003	0.032	-10000	0	-10000	0	0
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
DAB1/NCK2	0.003	0.036	-10000	0	-10000	0	0
ARHGEF2	0.025	0.005	-10000	0	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	0.008	0.012	-10000	0	-10000	0	0
CDK5R1	0.023	0.008	-10000	0	-10000	0	0
RELN	0.007	0.011	-10000	0	-10000	0	0
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
RELN/LRP8/Fyn	0.013	0.023	-10000	0	-10000	0	0
GRIN2A/RELN/LRP8/DAB1/Fyn	0.008	0.028	-10000	0	-10000	0	0
MAPK8	0.018	0.012	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	0.009	0.02	-10000	0	-0.02	2	2
ITGB1	0.017	0.015	-10000	0	-0.058	2	2
MAP1B	-0.013	0.041	0.14	8	-10000	0	8
RELN/LRP8	0.013	0.023	-10000	0	-10000	0	0
GRIN2B/RELN/LRP8/DAB1/Fyn	0.003	0.023	-10000	0	-10000	0	0
PI3K	0.036	0.01	-10000	0	0	10	10
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.028	0.019	-10000	0	0	43	43
RAP1A	0.03	0.1	0.22	16	-10000	0	16
PAFAH1B1	0.025	0.004	-10000	0	-10000	0	0
MAPK8IP1	0.025	0.004	-10000	0	-10000	0	0
CRLK/C3G	0.035	0.011	-10000	0	0	14	14
GRIN2B	0.008	0.011	-10000	0	-10000	0	0
NCK2	0.026	0.002	-10000	0	-10000	0	0
neuron differentiation	-0.049	0.079	-10000	0	-0.2	24	24
neuron adhesion	0.018	0.1	0.34	5	-10000	0	5
LRP8	0.025	0.005	-10000	0	-10000	0	0
GSK3B	-0.055	0.065	0.17	1	-0.18	18	19
RELN/VLDLR/DAB1/Fyn	0.007	0.026	-10000	0	-10000	0	0
MAP3K11	0.026	0.003	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.022	0.058	-10000	0	-0.16	19	19
CDK5	0.018	0.012	-10000	0	-10000	0	0
MAPT	-0.002	0.005	-10000	0	-10000	0	0
neuron migration	-0.069	0.096	0.2	6	-0.19	22	28
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.049	0.079	-10000	0	-0.2	24	24
RELN/VLDLR	0.014	0.029	-10000	0	-0.028	4	4

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.019	0.003	-10000	0	-10000	0	0
PRKCZ	0.019	0.011	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.025	0.006	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	0.015	0.03	-10000	0	-0.16	4	4
IRAK/TOLLIP	0.023	0.007	-10000	0	-10000	0	0
IKBKB	0.026	0.004	-10000	0	-10000	0	0
IKBKG	0.025	0.004	-10000	0	-10000	0	0
IL1 alpha/IL1R2	0.053	0.01	-10000	0	-10000	0	0
IL1A	0.026	0	-10000	0	-10000	0	0
IL1B	-0.025	0.009	0	2	-0.046	23	25
IRAK/TRAF6/p62/Atypical PKCs	0.037	0.041	0.18	1	-10000	0	1
IL1R2	-0.031	0.039	-10000	0	-0.058	100	100
IL1R1	0.024	0.014	-10000	0	-0.058	4	4
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.001	0.033	-10000	0	-10000	0	0
TOLLIP	0.025	0.006	-10000	0	-10000	0	0
TICAM2	0.026	0.003	-10000	0	-10000	0	0
MAP3K3	0.026	0.002	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.016	0.005	-10000	0	-10000	0	0
IKK complex/ELKS	-0.043	0.091	-10000	0	-0.23	7	7
JUN	-0.023	0.021	0.14	1	-10000	0	1
MAP3K7	0.024	0.008	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.06	0.031	0.16	1	-0.067	1	2
IL1 alpha/IL1R1/IL1RAP/MYD88	0.068	0.02	-10000	0	-0.036	4	4
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.074	0.029	-10000	0	-0.064	1	1
IL1 beta fragment/IL1R1/IL1RAP	0.026	0.035	-10000	0	-0.051	23	23
NFKB1	0.026	0.002	-10000	0	-10000	0	0
MAPK8	-0.019	0.025	0.15	2	-10000	0	2
IRAK1	-0.017	0.003	-10000	0	-10000	0	0
IL1RN/IL1R1	0.04	0.004	-10000	0	-10000	0	0
IRAK4	0.025	0.005	-10000	0	-10000	0	0
PRKCI	0.026	0.003	-10000	0	-10000	0	0
TRAF6	0.026	0.003	-10000	0	-10000	0	0
PI3K	0.036	0.01	-10000	0	0	10	10
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.01	0.031	-10000	0	-0.17	4	4
CHUK	0.018	0.012	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.026	0.035	-10000	0	-0.051	23	23
IL1 beta/IL1R2	0.046	0.016	-10000	0	-10000	0	0
IRAK/TRAF6/TAK1/TAB1/TAB2	0.027	0.017	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.006	0.055	-10000	0	-10000	0	0
IRAK3	0.024	0.01	-10000	0	-0.058	1	1
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.061	0.029	0.16	1	-0.067	1	2
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.011	0.031	-10000	0	-0.12	1	1
IL1 alpha/IL1R1/IL1RAP	0.055	0.015	-10000	0	-0.061	1	1
RELA	0.026	0.003	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.026	0.003	-10000	0	-10000	0	0
MYD88	0.026	0.002	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0.041	0.018	0.18	2	-10000	0	2
IL1RAP	0.011	0.032	-10000	0	-0.049	30	30
UBE2N	0.026	0.004	-10000	0	-10000	0	0
IRAK/TRAF6	-0.054	0.016	-10000	0	-10000	0	0
CASP1	0.013	0.031	-10000	0	-0.058	23	23
IL1RN/IL1R2	0.054	0.01	0.082	1	-10000	0	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.04	0.04	-10000	0	-0.051	20	20
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.012	0.031	-10000	0	-0.19	1	1
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
IL1RN	0.025	0.01	-10000	0	-0.058	2	2
TRAF6/TAK1/TAB1/TAB2	0.032	0.017	-10000	0	-0.018	14	14
MAP2K6	-0.021	0.027	0.17	3	-10000	0	3

×

Endothelins

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
AKT1	-0.042	0.019	-10000	0	-0.11	1	1
PTK2B	0.026	0.004	-10000	0	-10000	0	0
mol:Ca2+	-0.096	0.18	-10000	0	-0.4	31	31
EDN1	-0.017	0.032	-10000	0	-0.052	5	5
EDN3	0.021	0.013	-10000	0	-0.058	2	2
EDN2	0.011	0.03	-10000	0	-0.058	22	22
HRAS/GDP	0.01	0.082	0.25	4	-0.31	5	9
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	0.005	0.037	-10000	0	-0.19	2	2
ADCY4	-0.026	0.029	0.15	3	-10000	0	3
ADCY5	-0.023	0.03	0.15	3	-10000	0	3
ADCY6	-0.028	0.025	0.15	2	-10000	0	2
ADCY7	-0.027	0.029	0.15	3	-10000	0	3
ADCY1	-0.018	0.02	-10000	0	-10000	0	0
ADCY2	-0.026	0.029	0.15	3	-10000	0	3
ADCY3	-0.027	0.028	0.15	3	-10000	0	3
ADCY8	-0.025	0.028	0.15	3	-10000	0	3
ADCY9	-0.027	0.029	0.15	3	-10000	0	3
arachidonic acid secretion	-0.02	0.088	0.26	4	-0.33	5	9
ETB receptor/Endothelin-1/Gq/GTP	0.009	0.028	-10000	0	-0.2	2	2
GNAO1	0.024	0.007	-10000	0	-10000	0	0
HRAS	0.025	0.006	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	0.043	0.036	-10000	0	-0.096	1	1
ETA receptor/Endothelin-1/Gs/GTP	0.011	0.041	-10000	0	-0.072	1	1
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
COL3A1	-0.056	0.02	-10000	0	-0.11	2	2
EDNRB	0.017	0.02	-10000	0	-0.029	22	22
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.041	0.019	-10000	0	-0.11	1	1
CYSLTR1	-0.043	0.017	-10000	0	-0.11	1	1
SLC9A1	-0.009	0.015	-10000	0	-0.075	4	4
mol:GDP	-0.003	0.082	0.25	4	-0.32	5	9
SLC9A3	-0.033	0.17	-10000	0	-0.6	10	10
RAF1	-0.008	0.081	0.24	5	-0.32	5	10
JUN	-0.11	0.2	-10000	0	-0.45	29	29
JAK2	-0.039	0.022	-10000	0	-0.11	1	1
mol:IP3	-0.005	0.058	-10000	0	-0.27	5	5
ETA receptor/Endothelin-1	0.044	0.039	-10000	0	-0.076	12	12
PLCB1	0.023	0.009	-10000	0	-10000	0	0
PLCB2	0.025	0.005	-10000	0	-10000	0	0
ETA receptor/Endothelin-3	0.027	0.027	-10000	0	-0.046	11	11
FOS	-0.007	0.089	0.31	5	-0.32	4	9
Gai/GDP	-0.011	0.13	-10000	0	-0.49	10	10
CRK	0.026	0.004	-10000	0	-10000	0	0
mol:Ca ++	-0.019	0.044	-10000	0	-0.22	4	4
BCAR1	0.025	0.005	-10000	0	-10000	0	0
PRKCB1	-0.006	0.055	-10000	0	-0.25	5	5
GNAQ	0.026	0.005	-10000	0	-10000	0	0
GNAZ	0.025	0.006	-10000	0	-10000	0	0
GNAL	0.01	0.013	-10000	0	-10000	0	0
Gs family/GDP	-0.006	0.062	-10000	0	-0.29	5	5
ETA receptor/Endothelin-1/Gq/GTP	0.008	0.029	-10000	0	-0.18	2	2
MAPK14	-0.004	0.033	-10000	0	-0.18	3	3
TRPC6	-0.1	0.19	-10000	0	-0.42	31	31
GNAI2	0.026	0.003	-10000	0	-10000	0	0
GNAI3	0.026	0.003	-10000	0	-10000	0	0
GNAI1	0.017	0.012	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	0.005	0.037	-10000	0	-0.18	4	4
ETB receptor/Endothelin-2	0.038	0.013	-10000	0	-10000	0	0
ETB receptor/Endothelin-3	0.032	0.015	-10000	0	-10000	0	0
ETB receptor/Endothelin-1	0.02	0.038	-10000	0	-0.047	34	34
MAPK3	-0.004	0.089	0.3	6	-0.35	2	8
MAPK1	-0.008	0.094	0.3	6	-0.35	3	9
Rac1/GDP	0.006	0.059	0.27	2	-0.31	2	4
cAMP biosynthetic process	-0.043	0.06	0.15	2	-0.2	6	8
MAPK8	-0.12	0.23	-10000	0	-0.48	40	40
SRC	0.024	0.007	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	0.002	0.022	-10000	0	-10000	0	0
p130Cas/CRK/Src/PYK2	-0.004	0.09	0.32	4	-0.33	4	8
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	0.006	0.059	0.27	2	-0.31	2	4
COL1A2	-0.017	0.025	-10000	0	-0.12	2	2
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	0.031	0.031	-10000	0	-0.048	16	16
mol:DAG	-0.005	0.058	-10000	0	-0.27	5	5
MAP2K2	-0.005	0.098	0.35	6	-0.3	5	11
MAP2K1	-0.012	0.078	0.24	4	-0.3	5	9
EDNRA	-0.021	0.031	-10000	0	-0.064	6	6
positive regulation of muscle contraction	0.02	0.099	0.18	40	-10000	0	40
Gq family/GDP	0.037	0.071	0.18	1	-0.27	5	6
HRAS/GTP	-0.005	0.081	0.24	4	-0.33	5	9
PRKCH	-0.008	0.044	-10000	0	-0.25	3	3
RAC1	0.017	0.012	-10000	0	-10000	0	0
PRKCA	-0.012	0.055	-10000	0	-0.26	5	5
PRKCB	-0.001	0.021	-10000	0	-0.2	1	1
PRKCE	-0.012	0.054	-10000	0	-0.26	5	5
PRKCD	-0.011	0.057	0.19	1	-0.26	5	6
PRKCG	-0.003	0.021	-10000	0	-0.2	1	1
regulation of vascular smooth muscle contraction	-0.007	0.095	0.33	6	-0.36	2	8
PRKCQ	-0.006	0.041	0.19	1	-0.28	2	3
PLA2G4A	-0.022	0.092	0.26	4	-0.35	5	9
GNA14	0.026	0.005	-10000	0	-10000	0	0
GNA15	0.025	0.006	-10000	0	-10000	0	0
GNA12	0.017	0.012	-10000	0	-10000	0	0
GNA11	0.025	0.006	-10000	0	-10000	0	0
Rac1/GTP	0.043	0.036	-10000	0	-0.096	1	1
MMP1	-0.029	0.037	0.13	5	-10000	0	5

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	0.034	0.044	0.21	5	-10000	0	5
FYN	0.002	0.05	0.19	5	-0.2	1	6
LAT/GRAP2/SLP76	0.017	0.035	0.16	2	-10000	0	2
IKBKB	0.026	0.004	-10000	0	-10000	0	0
AKT1	0.001	0.048	0.13	3	-10000	0	3
B2M	0.018	0.025	0.058	1	-0.058	14	15
IKBKG	0.014	0.04	0.069	41	-10000	0	41
MAP3K8	0.018	0.013	-10000	0	-0.058	1	1
mol:Ca2+	-0.01	0.011	-10000	0	-10000	0	0
integrin-mediated signaling pathway	0.033	0.008	-10000	0	0	8	8
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.004	0.049	0.16	3	-10000	0	3
TRPV6	0.38	0.59	1.3	44	-10000	0	44
CD28	0.024	0.014	0.057	1	-0.059	4	5
SHC1	0.01	0.047	0.22	5	-10000	0	5
receptor internalization	0.014	0.022	0.14	1	-10000	0	1
PRF1	-0.16	0.28	-10000	0	-0.59	45	45
KRAS	0.025	0.006	-10000	0	-10000	0	0
GRB2	0.025	0.004	-10000	0	-10000	0	0
COT/AKT1	0.008	0.033	0.14	2	-10000	0	2
LAT	0.006	0.036	0.16	3	-10000	0	3
EntrezGene:6955	0	0.001	-10000	0	-10000	0	0
CD3D	0.011	0.032	0.06	1	-0.057	26	27
CD3E	0.022	0.018	0.062	1	-0.058	7	8
CD3G	0.016	0.026	-10000	0	-0.054	18	18
RASGRP2	0.002	0.011	-10000	0	-10000	0	0
RASGRP1	-0.002	0.065	0.19	6	-0.21	3	9
HLA-A	0	0.001	-10000	0	-10000	0	0
RASSF5	0.025	0.005	-10000	0	-10000	0	0
RAP1A/GTP/RAPL	0.033	0.008	-10000	0	0	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.019	0.043	0.15	9	-10000	0	9
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.013	0.016	-10000	0	-10000	0	0
PRKCA	-0.006	0.041	0.13	8	-10000	0	8
GRAP2	0.022	0.012	-10000	0	-0.058	2	2
mol:IP3	-0.009	0.027	-10000	0	-10000	0	0
EntrezGene:6957	0	0.001	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	0.01	0.016	-10000	0	-10000	0	0
ORAI1	-0.34	0.5	-10000	0	-1.1	44	44
CSK	0.008	0.037	0.17	4	-10000	0	4
B7 family/CD28	0.051	0.036	0.2	2	-10000	0	2
CHUK	0.018	0.012	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	0.012	0.029	0.15	2	-10000	0	2
PTPN6	0.004	0.038	0.18	5	-10000	0	5
VAV1	0.012	0.044	0.16	9	-10000	0	9
Monovalent TCR/CD3	0.013	0.003	-10000	0	-10000	0	0
CBL	0.026	0.002	-10000	0	-10000	0	0
LCK	0.007	0.045	0.18	6	-10000	0	6
PAG1	0.007	0.041	0.19	4	-10000	0	4
RAP1A	0.026	0.004	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	0.011	0.029	0.14	3	-10000	0	3
CD80	0.022	0.018	-10000	0	-0.058	7	7
CD86	0.025	0.008	-10000	0	-0.059	1	1
PDK1/CARD11/BCL10/MALT1	-0.007	0.022	-10000	0	-10000	0	0
HRAS	0.025	0.006	-10000	0	-10000	0	0
GO:0035030	-0.005	0.03	0.12	4	-10000	0	4
CD8A	0.026	0.001	-10000	0	-10000	0	0
CD8B	0.024	0.014	0.062	1	-0.058	4	5
PTPRC	0.025	0.008	-10000	0	-0.058	1	1
PDK1/PKC theta	0.004	0.056	0.18	8	-10000	0	8
CSK/PAG1	0.003	0.045	0.19	6	-10000	0	6
SOS1	0.026	0	-10000	0	-10000	0	0
peptide-MHC class I	0.021	0.007	0.04	15	-10000	0	15
GRAP2/SLP76	0.031	0.033	0.18	2	-10000	0	2
STIM1	-0.06	0.17	1	1	-1.1	2	3
RAS family/GTP	0.013	0.037	0.12	6	-0.16	2	8
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	0.014	0.023	0.14	1	-10000	0	1
mol:DAG	-0.017	0.015	-10000	0	-10000	0	0
RAP1A/GDP	0.012	0.02	0.073	8	-10000	0	8
PLCG1	0.023	0.008	-10000	0	-10000	0	0
CD247	0.026	0.004	-10000	0	-10000	0	0
cytotoxic T cell degranulation	-0.16	0.28	-10000	0	-0.57	45	45
RAP1A/GTP	0	0.005	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.004	0.046	0.15	4	-10000	0	4
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.005	0.034	-10000	0	-10000	0	0
NRAS	0.026	0.003	-10000	0	-10000	0	0
ZAP70	0.026	0	-10000	0	-10000	0	0
GRB2/SOS1	0.038	0.006	-10000	0	0	4	4
LAT/GRAP2/SLP76/VAV1	-0.002	0.041	0.16	5	-10000	0	5
MALT1	0.025	0.005	-10000	0	-10000	0	0
TRAF6	0.026	0.003	-10000	0	-10000	0	0
CD8 heterodimer	0.04	0.005	0.07	1	-10000	0	1
CARD11	0.017	0.012	-10000	0	-10000	0	0
PRKCB	-0.002	0.027	0.11	5	-10000	0	5
PRKCE	-0.004	0.043	0.14	9	-10000	0	9
PRKCQ	0.004	0.052	0.18	6	-10000	0	6
LCP2	0.025	0.008	-10000	0	-0.058	1	1
BCL10	0.025	0.005	-10000	0	-10000	0	0
regulation of survival gene product expression	0.002	0.045	0.12	4	-10000	0	4
IKK complex	-0.015	0.031	0.1	2	-0.083	1	3
RAS family/GDP	-0.002	0.006	-10000	0	-10000	0	0
MAP3K14	-0.005	0.027	0.1	3	-10000	0	3
PDPK1	0.001	0.045	0.14	5	-10000	0	5
TCR/CD3/MHC I/CD8/Fyn	0.015	0.029	-10000	0	-10000	0	0

×

EPHB forward signaling

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
Ephrin A5/EPHB2	0.032	0.01	-10000	0	0	13	13
cell-cell adhesion	0.029	0.023	-10000	0	-10000	0	0
Ephrin B/EPHB2/RasGAP	0.068	0.03	-10000	0	-10000	0	0
ITSN1	0.026	0.004	-10000	0	-10000	0	0
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
SHC1	0.023	0.013	-10000	0	-0.058	3	3
Ephrin B1/EPHB3	0.034	0.007	-10000	0	0	5	5
Ephrin B1/EPHB1	0.034	0.007	-10000	0	0	6	6
HRAS/GDP	0.018	0.043	-10000	0	-0.16	5	5
Ephrin B/EPHB1/GRB7	0.066	0.032	-10000	0	-10000	0	0
Endophilin/SYNJ1	-0.028	0.028	0.16	3	-10000	0	3
KRAS	0.025	0.006	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	0.063	0.034	-10000	0	-10000	0	0
endothelial cell migration	0.035	0.029	-10000	0	-0.029	5	5
GRB2	0.025	0.004	-10000	0	-10000	0	0
GRB7	0.023	0.01	-10000	0	-0.058	2	2
PAK1	-0.031	0.045	0.19	5	-10000	0	5
HRAS	0.025	0.006	-10000	0	-10000	0	0
RRAS	-0.025	0.042	0.21	4	-10000	0	4
DNM1	0.016	0.013	-10000	0	-10000	0	0
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.027	0.032	0.16	4	-10000	0	4
lamellipodium assembly	-0.029	0.023	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.019	0.026	-10000	0	-10000	0	0
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
EPHB2	0.026	0.004	-10000	0	-10000	0	0
EPHB3	0.025	0.004	-10000	0	-10000	0	0
EPHB1	0.025	0.005	-10000	0	-10000	0	0
EPHB4	0.017	0.015	-10000	0	-0.058	2	2
mol:GDP	-0.004	0.046	0.17	8	-0.14	2	10
Ephrin B/EPHB2	0.055	0.023	-10000	0	-0.026	9	9
Ephrin B/EPHB3	0.055	0.023	-10000	0	-0.026	8	8
JNK cascade	-0.026	0.045	0.2	5	-10000	0	5
Ephrin B/EPHB1	0.053	0.026	-10000	0	-0.026	10	10
RAP1/GDP	0.026	0.1	0.2	33	-0.18	3	36
EFNB2	0.025	0.006	-10000	0	-10000	0	0
EFNB3	0.025	0.004	-10000	0	-10000	0	0
EFNB1	0.025	0.007	-10000	0	-0.058	1	1
Ephrin B2/EPHB1-2	0.045	0.017	-10000	0	-0.02	6	6
RAP1B	0.023	0.01	-10000	0	-0.058	1	1
RAP1A	0.026	0.004	-10000	0	-10000	0	0
CDC42/GTP	0.052	0.037	0.14	1	-0.09	1	2
Rap1/GTP	-0.047	0.016	-10000	0	-10000	0	0
axon guidance	0.032	0.01	-10000	0	0	13	13
MAPK3	-0.004	0.038	0.17	2	-10000	0	2
MAPK1	-0.004	0.034	0.17	1	-10000	0	1
Rac1/GDP	-0.01	0.06	0.23	6	-0.18	3	9
actin cytoskeleton reorganization	-0.034	0.03	0.036	1	-0.14	4	5
CDC42/GDP	0.038	0.11	0.2	41	-0.18	3	44
PI3K	0.038	0.032	-10000	0	-0.042	1	1
EFNA5	0.024	0.007	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.024	0.017	-10000	0	0	48	48
Ephrin B/EPHB2/Intersectin/N-WASP	0.009	0.024	-10000	0	-10000	0	0
CDC42	0.026	0.004	-10000	0	-10000	0	0
RAS family/GTP	-0.049	0.013	-10000	0	-10000	0	0
PTK2	0.005	0.11	0.55	6	-10000	0	6
MAP4K4	-0.026	0.045	0.2	5	-10000	0	5
SRC	0.024	0.007	-10000	0	-10000	0	0
KALRN	0.025	0.005	-10000	0	-10000	0	0
Intersectin/N-WASP	0.027	0.018	-10000	0	0	46	46
neuron projection morphogenesis	0.066	0.16	0.3	44	-10000	0	44
MAP2K1	0.006	0.026	-10000	0	-10000	0	0
WASL	0.018	0.012	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	0.063	0.019	-10000	0	-0.027	2	2
cell migration	0	0.046	0.17	2	-10000	0	2
NRAS	0.026	0.003	-10000	0	-10000	0	0
SYNJ1	-0.028	0.028	0.16	3	-10000	0	3
PXN	0.026	0.003	-10000	0	-10000	0	0
TF	-0.031	0.025	0.15	2	-10000	0	2
HRAS/GTP	0.039	0.03	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2	0.047	0.013	-10000	0	-0.02	2	2
cell adhesion mediated by integrin	0.017	0.029	-10000	0	-0.18	2	2
RAC1	0.017	0.012	-10000	0	-10000	0	0
mol:GTP	0.045	0.027	0.14	1	-10000	0	1
RAC1-CDC42/GTP	-0.033	0.025	-10000	0	-10000	0	0
RASA1	0.026	0.004	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.015	0.055	0.22	5	-0.18	3	8
ruffle organization	0.071	0.16	0.31	43	-10000	0	43
NCK1	0.026	0.004	-10000	0	-10000	0	0
receptor internalization	-0.019	0.031	0.15	3	-10000	0	3
Ephrin B/EPHB2/KALRN	0.067	0.032	-10000	0	-10000	0	0
ROCK1	-0.015	0.036	0.18	5	-10000	0	5
RAS family/GDP	-0.033	0.03	-10000	0	-0.14	4	4
Rac1/GTP	-0.03	0.024	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src/Paxillin	0.01	0.03	-10000	0	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	0.034	0.007	-10000	0	0	6	6
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0.025	0.005	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.026	0.002	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.026	0.002	-10000	0	-10000	0	0
RAC1-CDC42/GTP/PAK family	0	0.019	-10000	0	-0.18	1	1
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.025	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	0.026	0.002	-10000	0	-10000	0	0
FYN	0.024	0.007	-10000	0	-10000	0	0
MAP3K12	0.026	0.004	-10000	0	-10000	0	0
FGR	0.025	0.005	-10000	0	-10000	0	0
p38 alpha/TAB1	-0.008	0.031	-10000	0	-0.23	2	2
PRKG1	0.018	0.012	-10000	0	-10000	0	0
DUSP8	0.023	0.009	-10000	0	-10000	0	0
PGK/cGMP/p38 alpha	0.02	0.052	0.14	2	-0.23	2	4
apoptosis	-0.008	0.03	-10000	0	-0.22	2	2
RAL/GTP	0.024	0.017	-10000	0	0	48	48
LYN	0.026	0.004	-10000	0	-10000	0	0
DUSP1	0.025	0.008	-10000	0	-0.058	1	1
PAK1	0.026	0.004	-10000	0	-10000	0	0
SRC	0.024	0.007	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.041	0.033	-10000	0	-0.028	2	2
TRAF6	0.026	0.003	-10000	0	-10000	0	0
RAC1	0.017	0.012	-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	0.018	0.012	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0.023	0.017	-10000	0	0	52	52
MAPK11	0.033	0.079	0.17	22	-0.22	1	23
BLK	0.021	0.014	-10000	0	-0.058	4	4
HCK	0.023	0.01	-10000	0	-0.058	1	1
MAP2K3	0.026	0.004	-10000	0	-10000	0	0
DUSP16	0.025	0.006	-10000	0	-10000	0	0
DUSP10	0.025	0.005	-10000	0	-10000	0	0
TRAF6/MEKK3	0.033	0.005	-10000	0	0	3	3
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.035	0.069	0.18	8	-0.25	2	10
positive regulation of innate immune response	0.039	0.087	0.19	21	-0.25	1	22
LCK	0.002	0.037	-10000	0	-0.058	40	40
p38alpha-beta/MKP7	0.044	0.086	0.19	20	-0.25	1	21
p38alpha-beta/MKP5	0.046	0.087	0.19	20	-0.25	1	21
PGK/cGMP	0.014	0.009	-10000	0	-10000	0	0
PAK2	0.025	0.005	-10000	0	-10000	0	0
p38alpha-beta/MKP1	0.046	0.088	0.19	21	-0.25	1	22
CDC42	0.026	0.004	-10000	0	-10000	0	0
RALB	0.026	0	-10000	0	-10000	0	0
RALA	0.018	0.012	-10000	0	-10000	0	0
PAK3	0.014	0.013	-10000	0	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	0.046	0.011	-10000	0	0	1	1
AKT1	-0.003	0.068	0.2	2	-0.27	3	5
PTK2B	-0.03	0.056	0.15	12	-10000	0	12
VEGFR2 homodimer/Frs2	0.021	0.009	-10000	0	-10000	0	0
CAV1	0.005	0.029	-10000	0	-0.058	22	22
CALM1	0.024	0.007	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.044	0.031	0.17	5	-0.059	1	6
endothelial cell proliferation	0.006	0.076	0.2	6	-0.24	3	9
mol:Ca2+	-0.018	0.053	0.16	11	-10000	0	11
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.044	0.043	0.17	8	-10000	0	8
RP11-342D11.1	-0.016	0.047	0.15	10	-10000	0	10
CDH5	0.026	0.003	-10000	0	-10000	0	0
VEGFA homodimer	0.062	0.031	-10000	0	-0.039	9	9
SHC1	0.023	0.013	-10000	0	-0.058	3	3
SHC2	0.025	0.006	-10000	0	-10000	0	0
HRAS/GDP	0.006	0.047	0.047	26	-10000	0	26
SH2D2A	0.025	0.008	-10000	0	-0.058	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.044	0.062	0.22	1	-10000	0	1
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.046	0.029	0.17	5	-0.059	1	6
VEGFR1 homodimer	0.024	0.007	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.071	0.039	0.16	10	-10000	0	10
GRB10	-0.015	0.042	0.17	6	-10000	0	6
PTPN11	0.025	0.004	-10000	0	-10000	0	0
GRB2	0.025	0.004	-10000	0	-10000	0	0
PAK1	0.026	0.004	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.071	0.038	0.18	9	-10000	0	9
HRAS	0.025	0.006	-10000	0	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	0.009	0.051	0.12	8	-0.23	3	11
HIF1A	0.025	0.006	-10000	0	-10000	0	0
FRS2	0.024	0.007	-10000	0	-10000	0	0
oxygen and reactive oxygen species metabolic process	0.037	0.036	0.17	3	-0.062	1	4
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.024	0.012	-10000	0	-0.058	3	3
Nck/Pak	0.037	0.008	-10000	0	0	6	6
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.043	0.031	0.17	5	-10000	0	5
mol:GDP	0.053	0.032	0.14	5	-10000	0	5
mol:NADP	0.019	0.059	-10000	0	-10000	0	0
eNOS/Hsp90	0.031	0.057	-10000	0	-10000	0	0
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
mol:IP3	-0.018	0.054	0.16	11	-10000	0	11
HIF1A/ARNT	0.036	0.011	-10000	0	0	12	12
SHB	0.024	0.008	-10000	0	-10000	0	0
VEGFA	0.002	0.038	-10000	0	-0.058	41	41
VEGFC	0.023	0.013	-10000	0	-0.058	3	3
FAK1/Vinculin	-0.002	0.049	0.16	2	-0.2	2	4
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.026	0.002	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.071	0.039	0.18	10	-10000	0	10
PTPN6	0.025	0.005	-10000	0	-10000	0	0
EPAS1	0.029	0.001	-10000	0	-10000	0	0
mol:L-citrulline	0.019	0.059	-10000	0	-10000	0	0
ITGAV	0.026	0.002	-10000	0	-10000	0	0
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.06	0.039	0.17	10	-10000	0	10
VEGFR2 homodimer/VEGFA homodimer	0.048	0.03	0.17	5	-10000	0	5
VEGFR2/3 heterodimer	0.023	0.008	-10000	0	-10000	0	0
VEGFB	0.026	0.002	-10000	0	-10000	0	0
MAPK11	-0.015	0.06	0.17	11	-0.18	1	12
VEGFR2 homodimer	-0.018	0.005	-10000	0	-10000	0	0
FLT1	0.024	0.007	-10000	0	-10000	0	0
NEDD4	0.025	0.008	-10000	0	-0.058	1	1
MAPK3	-0.016	0.058	0.15	4	-10000	0	4
MAPK1	-0.015	0.058	0.14	5	-10000	0	5
VEGFA145/NRP2	0.044	0.013	-10000	0	-10000	0	0
VEGFR1/2 heterodimer	0.021	0.009	-10000	0	-10000	0	0
KDR	-0.018	0.005	-10000	0	-10000	0	0
VEGFA165/NRP1/VEGFR2 homodimer	0.045	0.032	0.17	5	-10000	0	5
SRC	0.024	0.007	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	-0.012	0.067	0.15	7	-10000	0	7
PI3K	-0.02	0.048	0.15	6	-0.18	3	9
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.047	0.029	0.17	5	-0.059	1	6
FES	-0.021	0.054	0.16	11	-10000	0	11
GAB1	-0.014	0.063	0.15	8	-0.18	11	19
VEGFR2 homodimer/VEGFA homodimer/Src	0.043	0.031	0.17	5	-0.059	1	6
CTNNB1	0.026	0.002	-10000	0	-10000	0	0
SOS1	0.026	0	-10000	0	-10000	0	0
ARNT	0.026	0.004	-10000	0	-10000	0	0
eNOS/Caveolin-1	0.015	0.048	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Yes	0.046	0.03	0.17	5	-0.059	1	6
PI3K/GAB1	0.012	0.073	0.23	3	-0.26	3	6
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.067	0.041	0.18	9	-10000	0	9
PRKACA	0.025	0.006	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.037	0.019	0.17	1	-0.06	1	2
HSP90AA1	0.024	0.007	-10000	0	-10000	0	0
CDC42	-0.021	0.054	0.16	11	-10000	0	11
actin cytoskeleton reorganization	0.046	0.029	0.17	5	-10000	0	5
PTK2	0.002	0.057	0.15	9	-0.21	2	11
EDG1	-0.016	0.047	0.15	10	-10000	0	10
mol:DAG	-0.018	0.054	0.16	11	-10000	0	11
CaM/Ca2+	-0.02	0.053	0.16	11	-10000	0	11
MAP2K3	-0.026	0.049	0.15	10	-10000	0	10
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.097	0.091	0.22	48	-10000	0	48
PLCG1	-0.018	0.054	0.16	11	-10000	0	11
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.055	0.044	0.17	10	-10000	0	10
IQGAP1	0.026	0.004	-10000	0	-10000	0	0
YES1	0.025	0.005	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.046	0.03	0.17	5	-0.059	1	6
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.045	0.03	0.17	5	-10000	0	5
cell migration	0.009	0.063	0.2	4	-0.23	1	5
mol:PI-3-4-5-P3	-0.019	0.046	0.14	6	-0.17	3	9
FYN	0.024	0.007	-10000	0	-10000	0	0
VEGFB/NRP1	-0.02	0.051	0.16	11	-10000	0	11
mol:NO	0.019	0.059	-10000	0	-10000	0	0
PXN	0.026	0.003	-10000	0	-10000	0	0
HRAS/GTP	-0.043	0.019	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.006	0.056	0.16	14	-10000	0	14
VHL	0.026	0.004	-10000	0	-10000	0	0
ITGB3	-0.003	0.04	-10000	0	-0.058	50	50
NOS3	0.02	0.062	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Sck	0.044	0.029	0.17	4	-10000	0	4
RAC1	0.017	0.012	-10000	0	-10000	0	0
PRKCA	-0.022	0.053	0.15	12	-10000	0	12
PRKCB	-0.011	0.033	0.15	4	-10000	0	4
VCL	0.018	0.012	-10000	0	-10000	0	0
VEGFA165/NRP1	-0.014	0.054	0.18	10	-10000	0	10
VEGFR1/2 heterodimer/VEGFA homodimer	0.041	0.028	0.17	3	-0.059	1	4
VEGFA165/NRP2	0.044	0.013	-10000	0	-10000	0	0
MAPKKK cascade	-0.017	0.058	0.13	17	-10000	0	17
NRP2	0.026	0	-10000	0	-10000	0	0
VEGFC homodimer	0.023	0.013	-10000	0	-0.058	3	3
NCK1	0.026	0.004	-10000	0	-10000	0	0
ROCK1	0.025	0.005	-10000	0	-10000	0	0
FAK1/Paxillin	0.003	0.064	0.17	3	-0.21	2	5
MAP3K13	-0.023	0.049	0.16	9	-10000	0	9
PDPK1	-0.018	0.051	0.14	6	-0.16	3	9

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	0	0.06	-10000	0	-0.28	6	6
KLHL20	0.022	0.07	0.16	13	-0.17	5	18
CYFIP2	0.026	0.004	-10000	0	-10000	0	0
Rac1/GDP	0.001	0.05	0.17	7	-10000	0	7
ENAH	0.001	0.055	-10000	0	-0.28	5	5
AP1M1	0.025	0.005	-10000	0	-10000	0	0
RAP1B	0.023	0.01	-10000	0	-0.058	1	1
RAP1A	0.026	0.004	-10000	0	-10000	0	0
CTNNB1	0.026	0.002	-10000	0	-10000	0	0
CDC42/GTP	-0.025	0.041	0.11	10	-10000	0	10
ABI1/Sra1/Nap1	-0.014	0.023	-10000	0	-0.12	5	5
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.061	0.022	-10000	0	-0.027	5	5
RAPGEF1	0.001	0.066	0.16	11	-0.25	4	15
CTNND1	0.026	0.002	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.011	0.063	-10000	0	-0.28	6	6
CRK	0	0.068	0.16	9	-0.27	5	14
E-cadherin/gamma catenin/alpha catenin	0.049	0.015	-10000	0	-0.043	1	1
alphaE/beta7 Integrin	0.037	0.007	-10000	0	0	5	5
IQGAP1	0.026	0.004	-10000	0	0	3	3
NCKAP1	0.026	0	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.04	0.024	-10000	0	-0.02	15	15
DLG1	-0.001	0.06	-10000	0	-0.28	6	6
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.031	0.017	-10000	0	-0.087	2	2
MLLT4	0.023	0.008	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.045	0.019	-10000	0	-0.02	10	10
PI3K	-0.037	0.022	-10000	0	-0.11	1	1
ARF6	0.025	0.006	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
E-cadherin/gamma catenin	0.037	0.008	-10000	0	0	7	7
TIAM1	0.026	0.004	-10000	0	-10000	0	0
E-cadherin(dimer)/Ca2+	0.056	0.022	-10000	0	-0.026	6	6
AKT1	-0.016	0.037	0.13	1	-10000	0	1
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
CDH1	0.025	0.006	-10000	0	-10000	0	0
RhoA/GDP	-0.002	0.068	0.16	10	-10000	0	10
actin cytoskeleton organization	0.02	0.057	0.13	14	-0.13	5	19
CDC42/GDP	-0.004	0.066	0.16	8	-10000	0	8
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.008	0.022	-10000	0	-0.099	6	6
ITGB7	0.026	0.004	-10000	0	-10000	0	0
RAC1	0.017	0.012	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.061	0.023	-10000	0	-0.028	6	6
E-cadherin/Ca2+/beta catenin/alpha catenin	0.042	0.015	-10000	0	-0.019	5	5
mol:GDP	0	0.069	0.22	2	-10000	0	2
CDC42/GTP/IQGAP1	0.034	0.007	-10000	0	0	6	6
JUP	0.026	0.007	-10000	0	-0.058	1	1
p120 catenin/RhoA/GDP	-0.001	0.072	0.17	12	-10000	0	12
RAC1/GTP/IQGAP1	0.023	0.017	-10000	0	0	50	50
PIP5K1C/AP1M1	0.037	0.009	-10000	0	0	8	8
RHOA	0.026	0.002	-10000	0	-10000	0	0
CDC42	0.026	0.004	-10000	0	-10000	0	0
CTNNA1	0.026	0.004	-10000	0	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.015	0.041	0.099	14	-0.083	5	19
NME1	0.025	0.007	-10000	0	-0.058	1	1
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	0.001	0.054	-10000	0	-0.28	5	5
regulation of cell-cell adhesion	-0.03	0.018	0.047	1	-0.1	1	2
WASF2	0.003	0.03	0.064	12	-0.07	5	17
Rap1/GTP	-0.02	0.051	0.15	10	-10000	0	10
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.069	0.028	-10000	0	-0.049	1	1
CCND1	0.017	0.048	0.11	14	-0.1	5	19
VAV2	0.004	0.13	-10000	0	-0.59	5	5
RAP1/GDP	-0.011	0.055	0.16	10	-10000	0	10
adherens junction assembly	0.001	0.053	-10000	0	-0.27	5	5
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.018	0.012	-10000	0	-10000	0	0
PIP5K1C	0.025	0.006	-10000	0	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.046	0.024	0.18	1	-10000	0	1
E-cadherin/beta catenin	0	0.02	-10000	0	-0.12	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	0	0.055	-10000	0	-0.28	5	5
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
Rac1/GTP	-0.005	0.052	-10000	0	-0.26	5	5
E-cadherin/beta catenin/alpha catenin	0.049	0.014	-10000	0	-10000	0	0
ITGAE	0.026	0.004	-10000	0	0	3	3
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.011	0.064	-10000	0	-0.28	6	6

×

BCR signaling 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
JUN	0.004	0.074	0.22	2	-0.24	2	4
IKBKB	0.041	0.072	0.2	7	-0.3	2	9
AKT1	0.021	0.073	0.22	12	-10000	0	12
IKBKG	0.037	0.06	0.21	3	-0.22	2	5
CALM1	-0.013	0.048	-10000	0	-0.21	3	3
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
MAP3K1	0.032	0.074	0.26	4	-10000	0	4
MAP3K7	0.024	0.008	-10000	0	-10000	0	0
mol:Ca2+	-0.009	0.052	-10000	0	-0.19	6	6
DOK1	0.026	0	-10000	0	-10000	0	0
AP-1	-0.012	0.058	0.18	2	-0.2	4	6
LYN	0.026	0.004	-10000	0	-10000	0	0
BLNK	0.018	0.012	-10000	0	-10000	0	0
SHC1	0.023	0.013	-10000	0	-0.058	3	3
BCR complex	0.038	0.012	0.081	2	0	9	11
CD22	-0.006	0.012	-10000	0	-10000	0	0
CAMK2G	-0.007	0.04	-10000	0	-0.22	2	2
CSNK2A1	0.024	0.007	-10000	0	-10000	0	0
INPP5D	0.026	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.046	0.016	-10000	0	-10000	0	0
GO:0007205	-0.01	0.053	-10000	0	-0.2	6	6
SYK	0.025	0.008	-10000	0	-0.058	1	1
ELK1	-0.016	0.052	-10000	0	-0.21	3	3
NFATC1	-0.02	0.062	0.26	2	-0.22	5	7
B-cell antigen/BCR complex	0.038	0.012	0.081	2	0	9	11
PAG1/CSK	0.037	0.009	-10000	0	0	8	8
NFKBIB	0.03	0.034	0.12	4	-0.12	3	7
HRAS	-0.016	0.047	-10000	0	-0.22	1	1
NFKBIA	0.03	0.034	0.12	4	-0.12	3	7
NF-kappa-B/RelA/I kappa B beta	0.032	0.031	0.11	6	-0.095	2	8
RasGAP/Csk	0.08	0.032	-10000	0	-10000	0	0
mol:GDP	-0.007	0.054	-10000	0	-0.21	3	3
PTEN	0.016	0.013	-10000	0	-10000	0	0
CD79B	0.022	0.018	-10000	0	-0.058	7	7
NF-kappa-B/RelA/I kappa B alpha	0.032	0.031	0.11	6	-0.091	2	8
GRB2	0.025	0.004	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.005	0.066	0.27	1	-10000	0	1
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
mol:IP3	-0.009	0.053	-10000	0	-0.19	7	7
CSK	0.025	0.004	-10000	0	-10000	0	0
FOS	-0.018	0.049	-10000	0	-0.23	2	2
CHUK	-0.04	0.13	0.22	2	-0.24	36	38
IBTK	0.024	0.007	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	0.052	0.075	0.18	17	-0.2	3	20
PTPN6	-0.01	0.012	-10000	0	-10000	0	0
RELA	0.026	0.003	-10000	0	-10000	0	0
BCL2A1	0.02	0.021	0.075	5	-0.072	2	7
VAV2	-0.013	0.053	-10000	0	-0.25	5	5
ubiquitin-dependent protein catabolic process	0.031	0.034	0.12	4	-0.13	2	6
BTK	0.019	0.015	-10000	0	-10000	0	0
CD19	-0.01	0.021	-10000	0	-10000	0	0
MAP4K1	0.025	0.006	-10000	0	-10000	0	0
CD72	0.005	0.034	-10000	0	-0.058	32	32
PAG1	0.025	0.004	-10000	0	-10000	0	0
MAPK14	0.026	0.07	0.24	4	-10000	0	4
SH3BP5	0.026	0.002	-10000	0	-10000	0	0
PIK3AP1	0.008	0.024	-10000	0	-0.21	1	1
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	0.004	0.064	-10000	0	-0.3	5	5
RAF1	-0.02	0.044	-10000	0	-0.22	1	1
RasGAP/p62DOK/SHIP	0.08	0.029	-10000	0	-10000	0	0
CD79A	0.022	0.015	-10000	0	-0.058	4	4
re-entry into mitotic cell cycle	-0.013	0.057	0.18	2	-0.2	4	6
RASA1	0.026	0.004	-10000	0	-10000	0	0
MAPK3	-0.027	0.044	0.17	2	-0.2	1	3
MAPK1	-0.026	0.043	0.15	1	-0.2	1	2
CD72/SHP1	-0.007	0.049	0.2	6	-10000	0	6
NFKB1	0.026	0.002	-10000	0	-10000	0	0
MAPK8	0.027	0.067	0.24	4	-10000	0	4
actin cytoskeleton organization	0.037	0.08	0.29	3	-10000	0	3
NF-kappa-B/RelA	0.063	0.061	0.22	4	-0.2	2	6
Calcineurin	0.008	0.064	-10000	0	-0.22	2	2
PI3K	-0.029	0.036	-10000	0	-10000	0	0
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	0.013	0.023	-10000	0	-0.21	1	1
SOS1	0.026	0	-10000	0	-10000	0	0
Bam32/HPK1	0.037	0.055	-10000	0	-0.52	1	1
DAPP1	0.025	0.023	-10000	0	-10000	0	0
cytokine secretion	-0.019	0.06	0.25	2	-0.21	5	7
mol:DAG	-0.009	0.053	-10000	0	-0.19	7	7
PLCG2	0.025	0.005	-10000	0	-10000	0	0
MAP2K1	-0.024	0.044	0.16	1	-0.21	1	2
B-cell antigen/BCR complex/FcgammaRIIB	0.063	0.02	0.095	7	-10000	0	7
mol:PI-3-4-5-P3	-0.016	0.043	0.21	3	-10000	0	3
ETS1	-0.021	0.047	0.16	1	-0.26	1	2
B-cell antigen/BCR complex/LYN/SYK/BLNK	0.044	0.051	-10000	0	-10000	0	0
B-cell antigen/BCR complex/LYN	0.016	0.02	-10000	0	-10000	0	0
MALT1	0.025	0.005	-10000	0	-10000	0	0
TRAF6	0.026	0.003	-10000	0	-10000	0	0
RAC1	0.034	0.075	0.21	4	-10000	0	4
B-cell antigen/BCR complex/LYN/SYK	0.054	0.044	0.22	7	-10000	0	7
CARD11	0.033	0.088	0.19	30	-0.24	2	32
FCGR2B	-0.029	0.04	-10000	0	-0.058	95	95
PPP3CA	0.026	0.002	-10000	0	-10000	0	0
BCL10	0.025	0.005	-10000	0	-10000	0	0
IKK complex	0.01	0.041	0.13	6	-0.12	2	8
PTPRC	0.025	0.008	-10000	0	-0.058	1	1
PDPK1	-0.012	0.038	0.17	4	-10000	0	4
PPP3CB	0.018	0.012	-10000	0	-10000	0	0
PPP3CC	0.025	0.004	-10000	0	-10000	0	0
POU2F2	0.022	0.023	0.095	6	-0.073	1	7

×

IL23-mediated signaling events

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
CCL2	-0.11	0.23	-10000	0	-0.78	5	5
IL23A	-0.1	0.22	-10000	0	-0.76	6	6
NF kappa B1 p50/RelA/I kappa B alpha	-0.078	0.24	-10000	0	-0.72	8	8
positive regulation of T cell mediated cytotoxicity	-0.11	0.25	-10000	0	-0.8	7	7
ITGA3	-0.11	0.22	-10000	0	-0.76	5	5
IL17F	-0.093	0.18	-10000	0	-0.56	6	6
IL12B	0.006	0.036	-10000	0	-0.068	1	1
STAT1 (dimer)	-0.1	0.25	-10000	0	-0.76	8	8
CD4	-0.1	0.22	-10000	0	-0.78	5	5
IL23	-0.084	0.22	-10000	0	-0.7	8	8
IL23R	-0.012	0.078	-10000	0	-0.73	1	1
IL1B	-0.1	0.22	-10000	0	-0.76	7	7
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.1	0.23	-10000	0	-0.74	6	6
TYK2	0.006	0.033	-10000	0	-10000	0	0
STAT4	0.017	0.012	-10000	0	-10000	0	0
STAT3	0.026	0	-10000	0	-10000	0	0
IL18RAP	0.016	0.028	-10000	0	-0.058	18	18
IL12RB1	0.006	0.033	-10000	0	-10000	0	0
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	0.012	0.043	-10000	0	-10000	0	0
IL23R/JAK2	-0.001	0.087	-10000	0	-0.65	1	1
positive regulation of chronic inflammatory response	-0.11	0.25	-10000	0	-0.8	7	7
natural killer cell activation	0.002	0.005	-10000	0	-10000	0	0
JAK2	0.008	0.036	-10000	0	-0.067	2	2
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
NFKB1	0.012	0.023	-10000	0	-10000	0	0
RELA	0.012	0.023	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.082	0.22	-10000	0	-0.68	8	8
ALOX12B	-0.18	0.35	-10000	0	-0.86	26	26
CXCL1	-0.11	0.23	-10000	0	-0.78	5	5
T cell proliferation	-0.11	0.25	-10000	0	-0.8	7	7
NFKBIA	0.01	0.023	-10000	0	-10000	0	0
IL17A	-0.067	0.14	-10000	0	-0.44	6	6
PI3K	-0.09	0.24	-10000	0	-0.78	6	6
IFNG	-0.002	0.018	-10000	0	-0.091	3	3
STAT3 (dimer)	-0.082	0.24	-10000	0	-0.76	6	6
IL18R1	0.025	0.01	-10000	0	-0.058	2	2
IL23/IL23R/JAK2/TYK2/SOCS3	-0.066	0.16	-10000	0	-0.49	4	4
IL18/IL18R	0.058	0.01	0.11	1	-10000	0	1
macrophage activation	-0.007	0.013	-10000	0	-0.039	3	3
TNF	-0.11	0.23	-10000	0	-0.77	8	8
STAT3/STAT4	-0.1	0.24	-10000	0	-0.76	7	7
STAT4 (dimer)	-0.11	0.24	-10000	0	-0.78	7	7
IL18	0.025	0.01	-10000	0	-0.058	2	2
IL19	-0.11	0.23	-10000	0	-0.74	6	6
STAT5A (dimer)	-0.1	0.25	-10000	0	-0.76	8	8
STAT1	0.026	0.007	-10000	0	-0.058	1	1
SOCS3	0.025	0.007	-10000	0	-0.058	1	1
CXCL9	-0.11	0.23	-10000	0	-0.74	7	7
MPO	-0.17	0.34	-10000	0	-0.87	24	24
positive regulation of humoral immune response	-0.11	0.25	-10000	0	-0.8	7	7
IL23/IL23R/JAK2/TYK2	-0.11	0.25	-10000	0	-0.82	7	7
IL6	-0.054	0.23	-10000	0	-0.66	6	6
STAT5A	0.026	0	-10000	0	-10000	0	0
IL2	0.015	0.017	-10000	0	-0.021	23	23
positive regulation of tyrosine phosphorylation of STAT protein	0.002	0.005	-10000	0	-10000	0	0
CD3E	-0.11	0.22	-10000	0	-0.78	5	5
keratinocyte proliferation	-0.11	0.25	-10000	0	-0.8	7	7
NOS2	-0.11	0.24	-10000	0	-0.74	8	8

×

Plasma membrane estrogen receptor signaling

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
GNB1/GNG2	0.047	0.033	-10000	0	-10000	0	0
ER alpha/Gai/GDP/Gbeta gamma	-0.008	0.071	-10000	0	-0.42	2	2
AKT1	-0.029	0.18	-10000	0	-0.6	13	13
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.022	0.18	-10000	0	-0.61	13	13
mol:Ca2+	-0.003	0.044	0.16	7	-0.23	1	8
IGF1R	0.026	0.003	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	0.032	0.011	-10000	0	0	15	15
SHC1	0.023	0.013	-10000	0	-0.058	3	3
apoptosis	0.027	0.17	0.57	13	-10000	0	13
RhoA/GTP	-0.035	0.009	0	9	-10000	0	9
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	0.021	0.1	0.23	5	-0.29	5	10
regulation of stress fiber formation	0.031	0.044	-10000	0	-0.14	8	8
E2/ERA-ERB (dimer)	0.031	0.013	-10000	0	0	21	21
KRAS	0.025	0.006	-10000	0	-10000	0	0
G13/GTP	0.03	0.01	-10000	0	0	16	16
pseudopodium formation	-0.031	0.044	0.14	8	-10000	0	8
E2/ER alpha (dimer)/PELP1	0.031	0.012	-10000	0	0	18	18
GRB2	0.025	0.004	-10000	0	-10000	0	0
GNG2	0.025	0.006	-10000	0	-10000	0	0
GNAO1	0.024	0.007	-10000	0	-10000	0	0
HRAS	0.025	0.006	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.005	0.12	0.27	1	-0.46	5	6
E2/ER beta (dimer)	0.019	0.006	0.041	5	-10000	0	5
mol:GDP	-0.008	0.06	0.12	1	-0.19	12	13
mol:NADP	0.005	0.12	0.27	1	-0.46	5	6
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
mol:IP3	-0.01	0.021	-10000	0	-0.24	1	1
IGF-1R heterotetramer	0.026	0.003	-10000	0	-10000	0	0
PLCB1	0.003	0.01	-10000	0	-10000	0	0
PLCB2	0.003	0.011	-10000	0	-10000	0	0
IGF1	0.026	0.004	-10000	0	-10000	0	0
mol:L-citrulline	0.005	0.12	0.27	1	-0.46	5	6
RHOA	0.026	0.002	-10000	0	-10000	0	0
Gai/GDP	-0.01	0.13	-10000	0	-0.48	9	9
JNK cascade	0.019	0.006	0.04	5	-10000	0	5
BCAR1	0.025	0.005	-10000	0	-10000	0	0
ESR2	0.021	0.016	-10000	0	-0.058	5	5
GNAQ	0.025	0.005	-10000	0	-10000	0	0
ESR1	0.023	0.008	-10000	0	-10000	0	0
Gq family/GDP/Gbeta gamma	0.016	0.061	-10000	0	-0.46	1	1
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.033	0.03	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	0.024	0.099	0.23	5	-0.31	4	9
GNAZ	0.025	0.006	-10000	0	-10000	0	0
E2/ER alpha (dimer)	0.017	0.006	-10000	0	-10000	0	0
STRN	0.026	0	-10000	0	-10000	0	0
GNAL	0.01	0.013	-10000	0	-10000	0	0
PELP1	0.026	0.004	-10000	0	-10000	0	0
MAPK11	-0.015	0.007	-10000	0	-10000	0	0
GNAI2	0.026	0.003	-10000	0	-10000	0	0
GNAI3	0.026	0.003	-10000	0	-10000	0	0
GNAI1	0.017	0.012	-10000	0	-10000	0	0
HBEGF	0.007	0.13	0.3	13	-0.35	3	16
cAMP biosynthetic process	0.007	0.017	-10000	0	-0.017	13	13
SRC	-0.011	0.08	0.19	5	-0.4	2	7
PI3K	0.036	0.01	-10000	0	0	10	10
GNB1	0.025	0.006	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	0.022	0.066	-10000	0	-0.17	12	12
SOS1	0.026	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.006	0.069	-10000	0	-0.27	4	4
Gs family/GTP	0.009	0.021	-10000	0	-0.018	13	13
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.044	0.019	-10000	0	-0.02	9	9
vasodilation	0.006	0.12	0.27	1	-0.44	5	6
mol:DAG	-0.01	0.021	-10000	0	-0.24	1	1
Gs family/GDP/Gbeta gamma	-0.02	0.053	-10000	0	-0.17	12	12
MSN	-0.033	0.046	0.15	8	-10000	0	8
Gq family/GTP	0.016	0.013	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.021	0.18	-10000	0	-0.59	13	13
NRAS	0.026	0.003	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.006	0.12	0.44	5	-0.27	1	6
GRB2/SOS1	0.038	0.006	-10000	0	0	4	4
RhoA/GDP	0.006	0.064	0.13	1	-0.19	12	13
NOS3	0.004	0.13	0.28	1	-0.48	5	6
GNA11	0.025	0.006	-10000	0	-10000	0	0
MAPKKK cascade	-0.001	0.13	-10000	0	-0.4	13	13
E2/ER alpha (dimer)/PELP1/Src	0.02	0.1	0.22	9	-0.32	4	13
ruffle organization	-0.031	0.044	0.14	8	-10000	0	8
ROCK2	-0.027	0.056	0.18	9	-10000	0	9
GNA14	0.025	0.005	-10000	0	-10000	0	0
GNA15	0.025	0.006	-10000	0	-10000	0	0
GNA13	0.026	0.002	-10000	0	-10000	0	0
MMP9	-0.013	0.1	0.36	5	-0.35	3	8
MMP2	-0.003	0.098	0.23	6	-0.35	3	9

×

PDGFR-beta 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
S1P1/Sphingosine-1-phosphate	0.036	0.074	0.23	12	-0.23	2	14
PDGFB-D/PDGFRB/SLAP	0.038	0.009	-10000	0	0	7	7
PDGFB-D/PDGFRB/APS/CBL	0.037	0.025	-10000	0	-10000	0	0
AKT1	-0.016	0.077	0.3	3	-10000	0	3
mol:PI-4-5-P2	0	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.041	0.075	0.23	12	-0.26	2	14
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
FGR	0.009	0.046	0.19	1	-0.35	1	2
mol:Ca2+	0.031	0.073	0.22	11	-0.28	2	13
MYC	0.081	0.11	0.3	17	-10000	0	17
SHC1	0.023	0.013	-10000	0	-0.058	3	3
HRAS/GDP	-0.008	0.059	0.16	15	-10000	0	15
LRP1/PDGFRB/PDGFB	0.046	0.02	-10000	0	-10000	0	0
GRB10	0.017	0.013	-10000	0	-10000	0	0
PTPN11	0.025	0.004	-10000	0	-10000	0	0
GO:0007205	0.031	0.073	0.22	11	-0.29	2	13
PTEN	0.016	0.013	-10000	0	-10000	0	0
GRB2	0.025	0.004	-10000	0	-10000	0	0
GRB7	0.023	0.01	-10000	0	-0.058	2	2
PDGFB-D/PDGFRB/SHP2	0.038	0.008	-10000	0	0	6	6
PDGFB-D/PDGFRB/GRB10	0.025	0.019	-10000	0	0	55	55
cell cycle arrest	0.038	0.009	-10000	0	0	7	7
HRAS	0.025	0.006	-10000	0	-10000	0	0
HIF1A	-0.021	0.07	0.28	3	-10000	0	3
GAB1	0.03	0.076	0.22	10	-0.24	4	14
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	0.028	0.086	0.23	16	-0.22	2	18
PDGFB-D/PDGFRB	0.047	0.019	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.039	0.008	-10000	0	-10000	0	0
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.019	0.042	0.2	3	-0.23	1	4
positive regulation of MAPKKK cascade	0.038	0.008	-10000	0	0	6	6
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
mol:IP3	0.031	0.074	0.22	11	-0.29	2	13
E5	0	0.001	-10000	0	-10000	0	0
CSK	0.02	0.016	-10000	0	-0.026	14	14
PDGFB-D/PDGFRB/GRB7	0.038	0.006	0.066	1	-10000	0	1
SHB	0.024	0.008	-10000	0	-10000	0	0
BLK	0.009	0.046	-10000	0	-0.36	1	1
PTPN2	0.026	0.006	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.039	0.007	-10000	0	-10000	0	0
BCAR1	0.025	0.005	-10000	0	-10000	0	0
VAV2	0.033	0.081	0.24	10	-0.26	2	12
CBL	0.026	0.002	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.039	0.007	-10000	0	0	4	4
LCK	0.015	0.053	0.21	2	-0.35	1	3
PDGFRB	0.027	0.005	0.056	1	-10000	0	1
ACP1	0.026	0.004	-10000	0	-10000	0	0
HCK	0.01	0.028	-10000	0	-10000	0	0
ABL1	0.031	0.072	0.22	11	-0.23	1	12
PDGFB-D/PDGFRB/CBL	0.034	0.077	0.25	5	-0.29	3	8
PTPN1	0.024	0.008	-10000	0	-10000	0	0
SNX15	0.026	0.003	-10000	0	-10000	0	0
STAT3	0.026	0	-10000	0	-10000	0	0
STAT1	0.026	0.007	-10000	0	-0.058	1	1
cell proliferation	0.079	0.1	0.29	17	-10000	0	17
SLA	0.024	0.009	-10000	0	-0.058	1	1
actin cytoskeleton reorganization	-0.016	0.067	0.17	15	-10000	0	15
SRC	0.011	0.031	-10000	0	-10000	0	0
PI3K	-0.04	0.017	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	0.051	0.011	-10000	0	-10000	0	0
SH2B2	0.018	0.012	-10000	0	-10000	0	0
PLCgamma1/SPHK1	0.042	0.076	0.24	12	-0.26	2	14
LYN	0.013	0.035	-10000	0	-10000	0	0
LRP1	0.024	0.007	-10000	0	-10000	0	0
SOS1	0.026	0	-10000	0	-10000	0	0
STAT5B	0.026	0	-10000	0	-10000	0	0
STAT5A	0.026	0	-10000	0	-10000	0	0
NCK1-2/p130 Cas	0.064	0.036	-10000	0	-10000	0	0
SPHK1	0.026	0.009	-10000	0	-0.041	2	2
EDG1	0.001	0.003	-10000	0	-10000	0	0
mol:DAG	0.031	0.074	0.22	11	-0.29	2	13
PLCG1	0.031	0.075	0.22	11	-0.29	2	13
NHERF/PDGFRB	0.052	0.011	-10000	0	-10000	0	0
YES1	0.007	0.059	0.23	1	-0.57	1	2
cell migration	0.051	0.011	-10000	0	-10000	0	0
SHC/Grb2/SOS1	0.066	0.033	-10000	0	-10000	0	0
SLC9A3R2	0.026	0.004	-10000	0	-10000	0	0
SLC9A3R1	0.026	0.002	-10000	0	-10000	0	0
NHERF1-2/PDGFRB/PTEN	0.031	0.046	-10000	0	-0.03	1	1
FYN	-0.018	0.11	-10000	0	-0.39	11	11
DOK1	-0.008	0.061	0.17	16	-10000	0	16
HRAS/GTP	0.018	0.004	-10000	0	-10000	0	0
PDGFB	0.024	0.007	-10000	0	-10000	0	0
RAC1	0.083	0.11	0.31	16	-0.25	1	17
PRKCD	-0.006	0.063	0.17	16	-10000	0	16
FER	-0.007	0.061	0.17	15	-10000	0	15
MAPKKK cascade	-0.008	0.073	0.16	22	-10000	0	22
RASA1	-0.007	0.061	0.17	15	-10000	0	15
NCK1	0.026	0.004	-10000	0	-10000	0	0
NCK2	0.026	0.002	-10000	0	-10000	0	0
p62DOK/Csk	-0.015	0.057	0.16	14	-10000	0	14
PDGFB-D/PDGFRB/SHB	0.035	0.013	-10000	0	0	16	16
chemotaxis	0.031	0.071	0.22	11	-0.23	1	12
STAT1-3-5/STAT1-3-5	0.056	0.028	-10000	0	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0.02	0.004	0.042	1	-10000	0	1
PTPRJ	0.026	0.003	-10000	0	-10000	0	0

×

Visual signal transduction: Rods

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
mol:K +	0.026	0.004	-10000	0	-10000	0	0
GNAT1/GTP	0.018	0.003	-10000	0	-10000	0	0
Metarhodopsin II/Arrestin	0.024	0.013	-10000	0	0	34	34
PDE6G/GNAT1/GTP	0.038	0.009	-10000	0	0	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	0.024	0.004	-10000	0	-10000	0	0
GRK1	0.023	0.006	-10000	0	-10000	0	0
CNG Channel	-0.001	0.039	-10000	0	-0.052	1	1
mol:Na +	-0.014	0.03	-10000	0	-10000	0	0
mol:ADP	0.023	0.006	-10000	0	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.049	0.014	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	-0.006	0.037	-10000	0	-10000	0	0
CNGB1	0.007	0.01	-10000	0	-10000	0	0
RDH5	0.017	0.025	-10000	0	-0.058	14	14
SAG	0.021	0.003	-10000	0	-10000	0	0
mol:Ca2+	-0.031	0.037	0.32	1	-10000	0	1
Na + (4 Units)	-0.035	0.011	-10000	0	-10000	0	0
RGS9	0.026	0.002	-10000	0	-10000	0	0
GNB1/GNGT1	0.021	0.017	-10000	0	0	56	56
GNAT1/GDP	0.055	0.02	-10000	0	-10000	0	0
GUCY2D	0.022	0.012	-10000	0	-0.058	3	3
GNGT1	0.013	0.01	-10000	0	-10000	0	0
GUCY2F	0.023	0.003	-10000	0	-10000	0	0
GNB5	0.026	0.004	-10000	0	-10000	0	0
mol:GMP (4 units)	-0.033	0.009	-10000	0	-0.06	2	2
mol:11-cis-retinal	0.017	0.025	-10000	0	-0.058	14	14
mol:cGMP	0.032	0.026	-10000	0	-0.051	3	3
GNB1	0.025	0.006	-10000	0	-10000	0	0
Rhodopsin	0.03	0.018	-10000	0	0	37	37
SLC24A1	0.026	0.004	-10000	0	-10000	0	0
CNGA1	0.025	0.003	-10000	0	-10000	0	0
Metarhodopsin II	0.023	0.014	-10000	0	0	38	38
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.046	0.03	-10000	0	-0.029	1	1
RGS9BP	0.025	0.006	-10000	0	-10000	0	0
Metarhodopsin II/Transducin	0.003	0.016	-10000	0	-0.099	3	3
GCAP Family/Ca ++	0.036	0.02	-10000	0	-0.019	3	3
PDE6A/B	0.04	0.008	-10000	0	0	2	2
mol:Pi	0.049	0.014	-10000	0	-10000	0	0
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	0.027	0.023	-10000	0	-0.021	4	4
PDE6B	0.026	0	-10000	0	-10000	0	0
PDE6A	0.018	0.025	-10000	0	-0.058	14	14
PDE6G	0.007	0.036	-10000	0	-0.058	34	34
RHO	0.019	0.01	-10000	0	-10000	0	0
PDE6	0.075	0.028	-10000	0	-10000	0	0
GUCA1A	0.02	0.01	-10000	0	-10000	0	0
GC2/GCAP Family	0.047	0.027	-10000	0	-10000	0	0
GUCA1C	0.021	0.004	-10000	0	-10000	0	0
GUCA1B	0.025	0.004	-10000	0	-10000	0	0

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.017	0.011	-10000	0	-0.096	1	1
TRAF2/ASK1	0.031	0.012	-10000	0	0	20	20
ATM	0.026	0.002	-10000	0	-10000	0	0
MAP2K3	0.017	0.058	0.19	2	-0.34	1	3
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.014	0.054	0.2	3	-0.22	2	5
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.023	0.015	-10000	0	-0.058	4	4
TXN	0.004	0.001	-10000	0	-10000	0	0
CALM1	0.024	0.007	-10000	0	-10000	0	0
GADD45A	0.024	0.013	-10000	0	-0.058	3	3
GADD45B	0.025	0.006	-10000	0	-10000	0	0
MAP3K1	0.026	0.004	-10000	0	0	3	3
MAP3K6	0.025	0.004	-10000	0	-10000	0	0
MAP3K7	0.024	0.008	-10000	0	-10000	0	0
MAP3K4	0.024	0.007	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.034	0.013	-10000	0	0	20	20
TAK1/TAB family	0.003	0.021	0.07	13	-0.064	1	14
RAC1/OSM/MEKK3	0.032	0.024	-10000	0	-10000	0	0
TRAF2	0.025	0.005	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.017	0.04	-10000	0	-0.29	1	1
TRAF6	0.004	0.001	-10000	0	-10000	0	0
RAC1	0.017	0.012	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	0.012	0.013	-10000	0	-10000	0	0
CCM2	0.018	0.012	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	0.016	0.018	-10000	0	0	82	82
MAPK11	0.023	0.008	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.02	0.026	-10000	0	-0.02	8	8
OSM/MEKK3	0.026	0.018	-10000	0	0	47	47
TAOK1	0.009	0.001	-10000	0	0	4	4
TAOK2	0.009	0.001	-10000	0	0	3	3
TAOK3	0.009	0.001	-10000	0	0	4	4
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.026	0.004	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.023	0.008	-10000	0	-10000	0	0
MAP3K10	0.025	0.006	-10000	0	-10000	0	0
MAP3K3	0.026	0.002	-10000	0	-10000	0	0
TRX/ASK1	0.019	0.013	-10000	0	-0.11	1	1
GADD45/MTK1/MTK1	0.05	0.03	-10000	0	-0.048	2	2

×

Ras signaling in the CD4+ TCR pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.05	0.1	-9999	-0.37	6	6
MAP3K8	0.018	0.013	-9999	-0.058	1	1
FOS	-0.056	0.095	-9999	-0.38	6	6
PRKCA	0.026	0.002	-9999	-10000	0	0
PTPN7	0.015	0.028	-9999	-0.058	19	19
HRAS	0.025	0.006	-9999	-10000	0	0
PRKCB	0.012	0.013	-9999	-10000	0	0
NRAS	0.026	0.003	-9999	-10000	0	0
RAS family/GTP	0.044	0.019	-9999	-0.02	9	9
MAPK3	-0.025	0.075	-9999	-0.53	2	2
MAP2K1	-0.067	0.11	-9999	-0.22	47	47
ELK1	0.026	0	-9999	-10000	0	0
BRAF	0.004	0.006	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
MAPK1	-0.039	0.11	-9999	-0.49	7	7
RAF1	0.005	0.006	-9999	-10000	0	0
KRAS	0.025	0.006	-9999	-10000	0	0

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.014	0.059	-10000	0	-0.19	14	14
TBX21	-0.044	0.073	-10000	0	-0.48	1	1
B2M	0.017	0.026	-10000	0	-0.058	15	15
TYK2	0.026	0.011	-10000	0	-10000	0	0
IL12RB1	0.026	0.011	-10000	0	-10000	0	0
GADD45B	-0.013	0.06	-10000	0	-10000	0	0
IL12RB2	0.007	0.013	-10000	0	-10000	0	0
GADD45G	-0.018	0.088	-10000	0	-0.66	1	1
natural killer cell activation	0.007	0.005	-10000	0	-10000	0	0
RELB	0.025	0.006	-10000	0	-10000	0	0
RELA	0.026	0.003	-10000	0	-10000	0	0
IL18	0.025	0.012	-10000	0	-0.052	3	3
IL2RA	-0.021	0.036	-10000	0	-0.058	68	68
IFNG	0.02	0.009	-10000	0	-0.058	1	1
STAT3 (dimer)	-0.026	0.07	-10000	0	-0.45	1	1
HLA-DRB5	0	0	-10000	0	-10000	0	0
FASLG	-0.041	0.075	-10000	0	-0.48	1	1
NF kappa B2 p52/RelB	-0.044	0.077	-10000	0	-0.47	1	1
CD4	0.025	0.009	-10000	0	-0.058	1	1
SOCS1	-0.023	0.041	-10000	0	-0.058	84	84
EntrezGene:6955	0.001	0	-10000	0	-10000	0	0
CD3D	0.011	0.032	-10000	0	-0.058	26	26
CD3E	0.022	0.019	-10000	0	-0.058	8	8
CD3G	0.016	0.026	-10000	0	-0.058	16	16
IL12Rbeta2/JAK2	0.011	0.02	-10000	0	-10000	0	0
CCL3	-0.047	0.095	-10000	0	-0.91	1	1
CCL4	-0.044	0.073	-10000	0	-0.48	1	1
HLA-A	0	0	-10000	0	-10000	0	0
IL18/IL18R	0.063	0.018	-10000	0	-0.075	1	1
NOS2	-0.005	0.083	-10000	0	-0.82	1	1
IL12/IL12R/TYK2/JAK2/SPHK2	-0.013	0.057	-10000	0	-0.18	14	14
IL1R1	-0.044	0.073	-10000	0	-0.48	1	1
IL4	-0.025	0.009	-10000	0	-10000	0	0
JAK2	0.024	0.012	-10000	0	-10000	0	0
EntrezGene:6957	0.001	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	0.012	0.015	-10000	0	-10000	0	0
RAB7A	-0.007	0.071	-10000	0	-10000	0	0
lysosomal transport	-0.006	0.069	-10000	0	-10000	0	0
FOS	-0.044	0.17	-10000	0	-0.6	12	12
STAT4 (dimer)	-0.067	0.1	-10000	0	-0.46	4	4
STAT5A (dimer)	-0.035	0.083	-10000	0	-0.48	1	1
GZMA	-0.03	0.067	-10000	0	-0.46	1	1
GZMB	-0.031	0.064	-10000	0	-0.46	1	1
HLX	0.025	0.005	-10000	0	-10000	0	0
LCK	-0.047	0.075	0.28	1	-0.45	2	3
TCR/CD3/MHC II/CD4	0.013	0.015	-10000	0	-10000	0	0
IL2/IL2R	0.041	0.058	0.12	6	-0.042	44	50
MAPK14	-0.004	0.077	-10000	0	-0.49	1	1
CCR5	-0.011	0.057	-10000	0	-10000	0	0
IL1B	0.028	0.01	-10000	0	-10000	0	0
STAT6	-0.018	0.071	-10000	0	-0.37	5	5
STAT4	0.017	0.012	-10000	0	-10000	0	0
STAT3	0.026	0	-10000	0	-10000	0	0
STAT1	0.026	0.007	-10000	0	-0.058	1	1
NFKB1	0.026	0.002	-10000	0	-10000	0	0
NFKB2	0.018	0.012	-10000	0	-10000	0	0
IL12B	0.029	0.01	-10000	0	-10000	0	0
CD8A	0.026	0	-10000	0	-10000	0	0
CD8B	0.024	0.015	-10000	0	-0.058	5	5
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.014	0.059	0.18	14	-10000	0	14
IL2RB	0.019	0.021	-10000	0	-0.058	9	9
proteasomal ubiquitin-dependent protein catabolic process	-0.065	0.099	-10000	0	-0.43	4	4
IL2RG	0.02	0.022	-10000	0	-0.058	11	11
IL12	0.044	0.015	-10000	0	-10000	0	0
STAT5A	0.026	0	-10000	0	-10000	0	0
CD247	0.026	0.004	-10000	0	-10000	0	0
IL2	0.02	0.002	-10000	0	-10000	0	0
SPHK2	0.025	0.006	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.027	0.01	-10000	0	-10000	0	0
IL12/IL12R/TYK2/JAK2	-0.04	0.075	-10000	0	-0.52	1	1
MAP2K3	-0.009	0.073	-10000	0	-0.48	1	1
RIPK2	0.025	0.004	-10000	0	-10000	0	0
MAP2K6	-0.007	0.072	-10000	0	-0.48	1	1
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0	0	-10000	0	-10000	0	0
IL18RAP	0.016	0.029	-10000	0	-0.057	19	19
IL12Rbeta1/TYK2	0.04	0.015	-10000	0	-10000	0	0
EOMES	0.023	0.015	-10000	0	-10000	0	0
STAT1 (dimer)	-0.026	0.084	-10000	0	-0.43	1	1
T cell proliferation	0.012	0.077	-10000	0	-10000	0	0
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.025	0.012	-10000	0	-0.052	3	3
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.049	0.097	-10000	0	-10000	0	0
ATF2	-0.01	0.073	-10000	0	-0.47	1	1

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	0.044	0.011	-10000	0	-0.019	1	1
RGS9BP	0.025	0.006	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GRK1	0.023	0.006	-10000	0	-10000	0	0
mol:Na +	0.04	0.012	-10000	0	0	4	4
mol:ADP	-0.021	0.006	0	9	-0.046	1	10
GNAT2	0.025	0.004	-10000	0	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.049	0.014	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.032	0.008	-10000	0	0	8	8
GRK7	0.024	0.008	-10000	0	-0.058	1	1
CNGB3	0.022	0.005	-10000	0	-10000	0	0
Cone Metarhodopsin II/X-Arrestin	0.015	0.001	-10000	0	0	1	1
mol:Ca2+	-0.017	0.022	0.16	1	-10000	0	1
Cone PDE6	0.041	0.047	-10000	0	-10000	0	0
Cone Metarhodopsin II	0.03	0.008	-10000	0	0	9	9
Na + (4 Units)	0.028	0.035	-10000	0	-0.025	29	29
GNAT2/GDP	0.056	0.018	-10000	0	-10000	0	0
GNB5	0.026	0.004	-10000	0	-10000	0	0
mol:GMP (4 units)	-0.014	0.024	0.17	2	-10000	0	2
Cone Transducin	0.047	0.012	-10000	0	-0.02	1	1
SLC24A2	0.016	0.013	-10000	0	-10000	0	0
GNB3/GNGT2	0.037	0.009	-10000	0	0	7	7
GNB3	0.024	0.009	-10000	0	-0.058	1	1
GNAT2/GTP	0.019	0.003	-10000	0	0	2	2
CNGA3	-0.013	0.042	-10000	0	-0.058	68	68
ARR3	0.02	0.002	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
cGMP/Cone CNG Channel	0.041	0.012	-10000	0	0	4	4
mol:Pi	0.049	0.014	-10000	0	-10000	0	0
Cone CNG Channel	0.031	0.049	-10000	0	-0.046	26	26
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	0.016	0.013	-10000	0	-10000	0	0
RGS9	0.026	0.002	-10000	0	-10000	0	0
PDE6C	0.016	0.01	-10000	0	-10000	0	0
GNGT2	0.025	0.007	-10000	0	-0.058	1	1
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	0.023	0.006	-10000	0	-10000	0	0

×

Osteopontin-mediated 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
IKK alpha homodimer	-0.033	0.023	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.055	0.033	-10000	0	-0.19	1	1
alphaV/beta3 Integrin/Osteopontin/Src	0.046	0.011	-10000	0	-10000	0	0
AP1	-0.063	0.02	-10000	0	-10000	0	0
ILK	-0.04	0.015	-10000	0	-10000	0	0
bone resorption	-0.062	0.031	0.15	2	-10000	0	2
PTK2B	0.026	0.004	-10000	0	-10000	0	0
PYK2/p130Cas	0.061	0.032	-10000	0	-10000	0	0
ITGAV	0.026	0.002	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.049	0.013	-10000	0	0	3	3
alphaV/beta3 Integrin/Osteopontin	0.067	0.016	-10000	0	-10000	0	0
MAP3K1	-0.041	0.014	-10000	0	-10000	0	0
JUN	0.025	0.004	-10000	0	-10000	0	0
MAPK3	-0.045	0.013	-10000	0	-10000	0	0
MAPK1	-0.043	0.015	-10000	0	-10000	0	0
Rac1/GDP	0.013	0.009	-10000	0	-10000	0	0
NFKB1	0.026	0.002	-10000	0	-10000	0	0
MAPK8	-0.033	0.024	-10000	0	-10000	0	0
ITGB3	-0.003	0.04	-10000	0	-0.059	50	50
NFKBIA	-0.042	0.026	-10000	0	-0.15	4	4
FOS	0.024	0.008	-10000	0	-10000	0	0
CD44	-0.02	0.042	-10000	0	-0.058	79	79
CHUK	0.018	0.012	-10000	0	-10000	0	0
PLAU	-0.053	0.035	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.061	0.023	0.17	1	-10000	0	1
BCAR1	0.025	0.005	-10000	0	-10000	0	0
RELA	0.026	0.003	-10000	0	-10000	0	0
alphaV beta3 Integrin	0.047	0.011	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	-0.04	0.015	-10000	0	-10000	0	0
VAV3	-0.043	0.015	-10000	0	-10000	0	0
MAP3K14	-0.041	0.013	-10000	0	-10000	0	0
ROCK2	0.026	0.002	-10000	0	-10000	0	0
SPP1	0	0.039	-10000	0	-0.058	45	45
RAC1	0.017	0.012	-10000	0	-10000	0	0
Rac1/GTP	-0.031	0.024	-10000	0	-10000	0	0
MMP2	-0.059	0.044	0.27	1	-10000	0	1

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.026	0.01	-10000	0	-10000	0	0
EPHB2	0.026	0.004	-10000	0	-10000	0	0
Syndecan-2/TACI	0.018	0.004	-10000	0	-10000	0	0
LAMA1	0.024	0.011	-10000	0	-0.058	2	2
Syndecan-2/alpha2 ITGB1	0.029	0.037	0.17	1	-10000	0	1
HRAS	0.025	0.006	-10000	0	-10000	0	0
Syndecan-2/CASK	-0.007	0.001	-10000	0	-10000	0	0
ITGA5	0.012	0.03	-10000	0	-0.058	22	22
BAX	-0.013	0.009	-10000	0	-10000	0	0
EPB41	0.025	0.005	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	0.02	0.004	-10000	0	-10000	0	0
LAMA3	0.024	0.007	-10000	0	-10000	0	0
EZR	0.024	0.008	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	0.017	0.015	-10000	0	-0.058	2	2
Syndecan-2/MMP2	0.028	0.012	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.027	0.019	-10000	0	0	46	46
dendrite morphogenesis	0.021	0.005	-10000	0	-10000	0	0
Syndecan-2/GM-CSF	0.018	0.004	-10000	0	-10000	0	0
determination of left/right symmetry	-0.009	0.002	-10000	0	-10000	0	0
Syndecan-2/PKC delta	0.022	0.004	-10000	0	-10000	0	0
GNB2L1	0.026	0.003	-10000	0	-10000	0	0
MAPK3	-0.016	0.033	0.18	4	-10000	0	4
MAPK1	-0.015	0.033	0.18	4	-10000	0	4
Syndecan-2/RACK1	0.034	0.009	-10000	0	-10000	0	0
NF1	0.026	0.004	-10000	0	-10000	0	0
FGFR/FGF/Syndecan-2	-0.009	0.002	-10000	0	-10000	0	0
ITGA2	0.024	0.01	-10000	0	-0.058	2	2
MAPK8	-0.01	0.007	-10000	0	-10000	0	0
Syndecan-2/alpha2/beta1 Integrin	0.029	0.038	0.17	1	-0.041	2	3
Syndecan-2/Kininogen	0.018	0.005	-10000	0	-10000	0	0
ITGB1	0.017	0.015	-10000	0	-0.058	2	2
SRC	-0.02	0.024	0.17	2	-10000	0	2
Syndecan-2/CASK/Protein 4.1	0.019	0.005	-10000	0	-10000	0	0
extracellular matrix organization	0.021	0.006	-10000	0	-10000	0	0
actin cytoskeleton reorganization	0.026	0.01	-10000	0	-10000	0	0
Syndecan-2/Caveolin-2/Ras	0.025	0.019	-10000	0	-10000	0	0
Syndecan-2/Laminin alpha3	0.02	0.007	-10000	0	-10000	0	0
Syndecan-2/RasGAP	0.045	0.016	-10000	0	-10000	0	0
alpha5/beta1 Integrin	0.03	0.022	0.082	2	0	46	48
PRKCD	0.026	0.002	-10000	0	-10000	0	0
Syndecan-2 dimer	0.021	0.005	-10000	0	-10000	0	0
GO:0007205	0.001	0	-10000	0	-10000	0	0
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	-0.027	0.01	-10000	0	-10000	0	0
RHOA	0.026	0.002	-10000	0	-10000	0	0
SDCBP	0.025	0.004	-10000	0	-10000	0	0
TNFRSF13B	0.021	0.003	-10000	0	-10000	0	0
RASA1	0.026	0.004	-10000	0	-10000	0	0
alpha2/beta1 Integrin	0.027	0.019	-10000	0	0	46	46
Syndecan-2/Synbindin	0.022	0.004	-10000	0	-10000	0	0
TGFB1	0.025	0.006	-10000	0	-10000	0	0
CASP3	-0.015	0.034	0.18	4	-10000	0	4
FN1	0.008	0.034	-10000	0	-0.058	31	31
Syndecan-2/IL8	0.027	0.011	-10000	0	-10000	0	0
SDC2	-0.009	0.002	-10000	0	-10000	0	0
KNG1	0.021	0.004	-10000	0	-10000	0	0
Syndecan-2/Neurofibromin	0.021	0.005	-10000	0	-10000	0	0
TRAPPC4	0.026	0.002	-10000	0	-10000	0	0
CSF2	0.02	0.002	-10000	0	-10000	0	0
Syndecan-2/TGFB1	0.021	0.006	-10000	0	-10000	0	0
Syndecan-2/Syntenin/PI-4-5-P2	0.02	0.004	-10000	0	-10000	0	0
Syndecan-2/Ezrin	0.033	0.013	-10000	0	-10000	0	0
PRKACA	-0.013	0.037	0.18	5	-10000	0	5
angiogenesis	0.027	0.011	-10000	0	-10000	0	0
MMP2	-0.003	0.04	-10000	0	-0.058	49	49
IL8	0.004	0.037	-10000	0	-0.058	38	38
calcineurin-NFAT signaling pathway	0.018	0.004	-10000	0	-10000	0	0

×

p75(NTR)-mediated signaling

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
Sortilin/TRAF6	0.038	0.006	-10000	0	0	4	4
Necdin/E2F1	0.033	0.014	-10000	0	0	23	23
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.075	0.023	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/BEX1	0.052	0.016	-10000	0	-10000	0	0
NT-4/5 (dimer)/p75(NTR)	0.038	0.013	0.082	2	0	9	11
IKBKB	0.026	0.004	-10000	0	-10000	0	0
AKT1	-0.025	0.049	0.2	6	-10000	0	6
IKBKG	0.025	0.004	-10000	0	-10000	0	0
BDNF	0.017	0.013	-10000	0	-10000	0	0
MGDIs/NGR/p75(NTR)/LINGO1	0.037	0.028	-10000	0	-10000	0	0
FURIN	0.026	0.004	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	0.035	0.027	-10000	0	-10000	0	0
LINGO1	0.024	0.008	-10000	0	-10000	0	0
Sortilin/TRAF6/NRIF	-0.045	0.014	-10000	0	-10000	0	0
proBDNF (dimer)	0.017	0.013	-10000	0	-10000	0	0
NTRK1	0.02	0.021	-10000	0	-0.058	9	9
RTN4R	0.018	0.012	-10000	0	-10000	0	0
neuron apoptosis	-0.01	0.07	0.27	1	-0.4	3	4
IRAK1	0.026	0.004	-10000	0	-10000	0	0
SHC1	-0.028	0.01	-10000	0	-0.045	23	23
ARHGDIA	0.026	0	-10000	0	-10000	0	0
RhoA/GTP	0.019	0.002	-10000	0	-10000	0	0
Gamma Secretase	0.063	0.035	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.068	0.013	-10000	0	-10000	0	0
MAGEH1	0.026	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	0.062	0.024	-10000	0	-0.028	3	3
Mammalian IAPs/DIABLO	0.065	0.015	-10000	0	-0.028	2	2
proNGF (dimer)	0.025	0.004	-10000	0	-10000	0	0
MAGED1	0.026	0	-10000	0	-10000	0	0
APP	0.026	0.004	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.02	0.014	-10000	0	-0.058	4	4
ZNF274	0.025	0.006	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	0.021	0.029	0.15	1	-10000	0	1
NGF	0.025	0.004	-10000	0	-10000	0	0
cell cycle arrest	-0.032	0.044	0.3	2	-10000	0	2
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.017	0.014	-10000	0	-10000	0	0
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.051	0.016	0.092	2	-10000	0	2
NCSTN	0.026	0.003	-10000	0	-10000	0	0
mol:GTP	0.051	0.016	-10000	0	-0.043	1	1
PSENEN	0.025	0.006	-10000	0	-10000	0	0
mol:ceramide	-0.028	0.02	0.17	1	-10000	0	1
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.01	0.043	-10000	0	-0.16	1	1
p75(NTR)/beta APP	0.041	0.01	-10000	0	0	4	4
BEX1	0.025	0.006	-10000	0	-10000	0	0
mol:GDP	-0.02	0.008	-10000	0	-10000	0	0
NGF (dimer)	0.063	0.036	-10000	0	-0.035	15	15
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.045	0.037	-10000	0	-0.028	7	7
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
RAC1/GTP	0.032	0.024	-10000	0	-10000	0	0
MYD88	0.026	0.002	-10000	0	-10000	0	0
CHUK	0.018	0.012	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	0.052	0.016	-10000	0	-0.043	1	1
RHOB	0.026	0.003	-10000	0	-10000	0	0
RHOA	0.026	0.002	-10000	0	-10000	0	0
MAGE-G1/E2F1	0.034	0.012	-10000	0	0	17	17
NT3 (dimer)	0.021	0.011	-10000	0	-0.058	2	2
TP53	-0.025	0.045	0.15	8	-10000	0	8
PRDM4	-0.03	0.019	0.17	1	-10000	0	1
BDNF (dimer)	0.029	0.048	-10000	0	-0.031	41	41
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
SORT1	0.026	0.003	-10000	0	-10000	0	0
activation of caspase activity	0.068	0.021	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.067	0.017	-10000	0	-0.028	2	2
RHOC	0.022	0.018	-10000	0	-0.058	7	7
XIAP	0.026	0.002	-10000	0	-10000	0	0
MAPK10	0.02	0.079	0.18	15	-10000	0	15
DIABLO	0.026	0.004	-10000	0	-10000	0	0
SMPD2	-0.028	0.02	0.17	1	-10000	0	1
APH1B	0.026	0.004	-10000	0	-10000	0	0
APH1A	0.026	0.003	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	0.054	0.011	-10000	0	-10000	0	0
PSEN1	0.024	0.007	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.037	0.008	-10000	0	0	7	7
NT3 (dimer)/p75(NTR)	0.038	0.012	0.082	1	0	8	9
MAPK8	-0.004	0.066	0.18	7	-10000	0	7
MAPK9	0.021	0.08	0.17	17	-10000	0	17
APAF1	0.026	0.004	-10000	0	-10000	0	0
NTF3	0.021	0.011	-10000	0	-0.058	2	2
NTF4	0.02	0.014	-10000	0	-0.058	4	4
NDN	0.024	0.007	-10000	0	-10000	0	0
RAC1/GDP	0.013	0.009	-10000	0	-10000	0	0
RhoA-B-C/GDP	0.065	0.025	-10000	0	-0.051	1	1
p75 CTF/Sortilin/TRAF6/NRIF	0.06	0.023	-10000	0	-0.028	6	6
RhoA-B-C/GTP	0.051	0.016	-10000	0	-0.043	1	1
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.042	0.048	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.042	0.037	-10000	0	-0.029	10	10
PRKACB	0.025	0.005	-10000	0	-10000	0	0
proBDNF (dimer)/p75 ECD	0.025	0.019	-10000	0	0	54	54
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.024	0.012	-10000	0	-0.058	3	3
BIRC2	0.026	0.002	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.025	0.014	-10000	0	-0.14	1	1
BAD	0.013	0.076	0.26	6	-10000	0	6
RIPK2	0.025	0.004	-10000	0	-10000	0	0
NGFR	0.013	0.03	-10000	0	-0.058	22	22
CYCS	-0.022	0.035	0.34	1	-10000	0	1
ADAM17	0.026	0.002	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.065	0.02	-10000	0	-0.028	2	2
BCL2L11	0.013	0.076	0.26	6	-10000	0	6
BDNF (dimer)/p75(NTR)	0.027	0.021	-10000	0	0	53	53
PI3K	0.063	0.023	-10000	0	-0.028	4	4
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.064	0.023	-10000	0	-0.035	5	5
NDNL2	0.025	0.005	-10000	0	-10000	0	0
YWHAE	0.026	0.004	-10000	0	-10000	0	0
PRKCI	0.026	0.003	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	0.041	0.01	-10000	0	0	4	4
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.068	0.013	-10000	0	-10000	0	0
TRAF6	0.026	0.003	-10000	0	-10000	0	0
RAC1	0.017	0.012	-10000	0	-10000	0	0
PRKCZ	0.019	0.011	-10000	0	-10000	0	0
PLG	0.019	0.006	-10000	0	-10000	0	0
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.031	0.012	-10000	0	-10000	0	0
SQSTM1	0.026	0.003	-10000	0	-10000	0	0
NGFRAP1	0.026	0.002	-10000	0	-10000	0	0
CASP3	0.012	0.073	0.24	6	-10000	0	6
E2F1	0.024	0.007	-10000	0	-10000	0	0
CASP9	0.025	0.005	-10000	0	-10000	0	0
IKK complex	0.004	0.068	-10000	0	-0.17	1	1
NGF (dimer)/TRKA	0.038	0.009	-10000	0	0	6	6
MMP7	-0.032	0.039	-10000	0	-0.058	101	101
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.071	0.028	-10000	0	-10000	0	0
MMP3	0.019	0.012	-10000	0	-0.058	1	1
APAF-1/Caspase 9	-0.041	0.031	-10000	0	-10000	0	0

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.039	0.04	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	0.025	0.006	-10000	0	-10000	0	0
STAT1 (dimer)/Cbp/p300	-0.031	0.06	0.22	7	-10000	0	7
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.042	0.026	0.15	1	-0.032	3	4
antigen processing and presentation of peptide antigen via MHC class I	-0.04	0.033	-10000	0	-0.11	10	10
CaM/Ca2+	0.038	0.044	-10000	0	-10000	0	0
RAP1A	0.026	0.004	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	-0.029	0.032	0.14	5	-10000	0	5
AKT1	-0.02	0.074	0.23	8	-10000	0	8
MAP2K1	-0.027	0.048	0.15	9	-10000	0	9
MAP3K11	-0.021	0.059	0.19	9	-10000	0	9
IFNGR1	0.02	0.017	0.075	2	-10000	0	2
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.12	0.14	-10000	0	-0.26	71	71
Rap1/GTP	-0.044	0.018	-10000	0	-10000	0	0
CRKL/C3G	0.035	0.011	-10000	0	0	14	14
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.049	0.047	-10000	0	-10000	0	0
CEBPB	-0.001	0.096	0.37	3	-0.44	2	5
STAT3	0.026	0	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.04	0.098	-10000	0	-0.73	2	2
STAT1	-0.022	0.06	0.19	9	-10000	0	9
CALM1	0.024	0.007	-10000	0	-10000	0	0
IFN-gamma (dimer)	-0.005	0.024	-10000	0	-0.063	1	1
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
STAT1 (dimer)/PIAS1	-0.022	0.066	0.19	11	-10000	0	11
CEBPB/PTGES2/Cbp/p300	0.008	0.059	-10000	0	-0.27	3	3
mol:Ca2+	0.037	0.039	-10000	0	-10000	0	0
MAPK3	-0.002	0.085	0.52	1	-0.69	1	2
STAT1 (dimer)	-0.051	0.042	-10000	0	-0.15	5	5
MAPK1	-0.026	0.15	0.52	1	-0.69	6	7
JAK2	0.021	0.016	0.075	2	-10000	0	2
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
JAK1	0.018	0.02	0.063	1	-10000	0	1
CAMK2D	0.026	0.002	-10000	0	-10000	0	0
DAPK1	0.001	0.071	0.32	3	-0.34	1	4
SMAD7	-0.02	0.03	0.086	3	-10000	0	3
CBL/CRKL/C3G	-0.026	0.067	0.2	10	-10000	0	10
PI3K	0.034	0.046	-10000	0	-10000	0	0
IFNG	-0.005	0.024	-10000	0	-0.063	1	1
apoptosis	0.005	0.061	0.35	2	-10000	0	2
CAMK2G	0.018	0.012	-10000	0	-10000	0	0
STAT3 (dimer)	0.026	0	-10000	0	-10000	0	0
CAMK2A	0.006	0.011	-10000	0	-10000	0	0
CAMK2B	0.012	0.013	-10000	0	-10000	0	0
FRAP1	-0.019	0.07	0.22	8	-10000	0	8
PRKCD	-0.023	0.076	0.25	7	-10000	0	7
RAP1B	0.023	0.01	-10000	0	-0.058	1	1
negative regulation of cell growth	-0.04	0.033	-10000	0	-0.11	10	10
PTPN2	0.025	0.005	-10000	0	-10000	0	0
EP300	0.024	0.007	-10000	0	-10000	0	0
IRF1	-0.033	0.051	0.26	3	-10000	0	3
STAT1 (dimer)/PIASy	-0.024	0.057	0.17	10	-10000	0	10
SOCS1	0.005	0.12	-10000	0	-1	2	2
mol:GDP	-0.026	0.063	0.19	10	-10000	0	10
CASP1	-0.018	0.049	0.21	3	-10000	0	3
PTGES2	0.025	0.006	-10000	0	-10000	0	0
IRF9	-0.004	0.039	0.17	3	-0.15	1	4
mol:PI-3-4-5-P3	0.022	0.039	-10000	0	-10000	0	0
RAP1/GDP	-0.042	0.029	0.1	4	-10000	0	4
CBL	-0.021	0.059	0.19	9	-10000	0	9
MAP3K1	-0.025	0.041	0.15	7	-10000	0	7
PIAS1	0.026	0.004	-10000	0	-10000	0	0
PIAS4	0.025	0.006	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.04	0.033	-10000	0	-0.11	10	10
PTPN11	-0.019	0.05	0.18	8	-10000	0	8
CREBBP	0.026	0.004	-10000	0	-10000	0	0
RAPGEF1	0.025	0.006	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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	-0.019	0.007	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.033	0.014	-10000	0	-10000	0	0
CDKN1B	-0.007	0.086	0.18	4	-0.32	9	13
CDKN1A	-0.007	0.073	0.16	1	-0.31	7	8
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.026	0.004	-10000	0	-10000	0	0
FOXO3	-0.005	0.075	0.17	2	-0.32	7	9
AKT1	-0.005	0.085	-10000	0	-0.33	9	9
BAD	0.026	0.002	-10000	0	-10000	0	0
AKT3	0.008	0.002	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	-0.009	0.079	0.16	1	-0.32	8	9
AKT1/ASK1	0.009	0.083	-10000	0	-0.3	9	9
BAD/YWHAZ	0.048	0.015	-10000	0	-10000	0	0
RICTOR	0.025	0.004	-10000	0	-10000	0	0
RAF1	0.026	0.002	-10000	0	-10000	0	0
JNK cascade	-0.009	0.081	0.29	9	-10000	0	9
TSC1	-0.009	0.077	0.16	1	-0.31	8	9
YWHAZ	0.025	0.005	-10000	0	-10000	0	0
AKT1/RAF1	0.011	0.09	-10000	0	-0.31	10	10
EP300	0.024	0.007	-10000	0	-10000	0	0
mol:GDP	-0.005	0.084	-10000	0	-0.32	9	9
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	-0.012	0.081	-10000	0	-0.32	9	9
YWHAQ	0.026	0.002	-10000	0	-10000	0	0
TBC1D4	-0.007	0.003	-10000	0	-10000	0	0
MAP3K5	0.023	0.008	-10000	0	-10000	0	0
MAPKAP1	0.025	0.006	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.025	0.055	0.19	2	-0.16	1	3
YWHAH	0.024	0.007	-10000	0	-10000	0	0
AKT1S1	-0.009	0.078	0.19	1	-0.32	8	9
CASP9	-0.009	0.085	0.19	2	-0.32	9	11
YWHAB	0.024	0.007	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.008	0.092	0.2	4	-0.3	10	14
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.044	0.02	-10000	0	-10000	0	0
YWHAE	0.026	0.004	-10000	0	-10000	0	0
SRC	0.024	0.007	-10000	0	-10000	0	0
AKT2/p21CIP1	-0.011	0.076	0.23	1	-0.27	10	11
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.003	0.027	-10000	0	-10000	0	0
CHUK	-0.005	0.053	-10000	0	-0.31	4	4
BAD/BCL-XL	0.003	0.086	-10000	0	-0.3	10	10
mTORC2	0.031	0.009	-10000	0	0	12	12
AKT2	0.008	0.002	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.01	0.075	0.19	1	-0.29	4	5
PDPK1	0.025	0.004	-10000	0	-10000	0	0
MDM2	0.01	0.093	0.19	14	-0.32	7	21
MAPKKK cascade	-0.011	0.089	0.3	10	-10000	0	10
MDM2/Cbp/p300	0.028	0.099	0.21	12	-0.3	9	21
TSC1/TSC2	-0.013	0.092	0.26	4	-0.31	10	14
proteasomal ubiquitin-dependent protein catabolic process	0.027	0.095	0.2	12	-0.29	9	21
glucose import	-0.011	0.018	0.2	1	-10000	0	1
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.007	0.058	0.17	5	-0.18	9	14
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.011	0.018	0.2	1	-10000	0	1
GSK3A	-0.009	0.078	0.19	1	-0.32	8	9
FOXO1	-0.01	0.077	0.16	1	-0.32	8	9
GSK3B	-0.007	0.079	0.19	1	-0.31	8	9
SFN	0.024	0.013	-10000	0	-0.058	3	3
G1/S transition of mitotic cell cycle	-0.013	0.091	0.21	5	-0.31	10	15
p27Kip1/14-3-3 family	0.036	0.048	0.18	1	-10000	0	1
PRKACA	0.025	0.006	-10000	0	-10000	0	0
KPNA1	0.026	0.004	-10000	0	-10000	0	0
HSP90AA1	0.024	0.007	-10000	0	-10000	0	0
YWHAG	0.018	0.012	-10000	0	-10000	0	0
RHEB	0.018	0.012	-10000	0	-10000	0	0
CREBBP	0.026	0.004	-10000	0	-10000	0	0

×

HIF-2-alpha transcription factor network

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
MMP14	-0.032	0.18	-10000	0	-0.62	13	13
oxygen homeostasis	-0.001	0.002	-10000	0	-10000	0	0
TCEB2	0.025	0.004	-10000	0	-10000	0	0
TCEB1	0.025	0.005	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.007	0.075	-10000	0	-0.17	7	7
EPO	-0.01	0.061	-10000	0	-0.22	7	7
FIH (dimer)	0.017	0.014	-10000	0	-10000	0	0
APEX1	0.026	0.009	-10000	0	-10000	0	0
SERPINE1	-0.024	0.05	-10000	0	-0.18	5	5
FLT1	-0.015	0.16	-10000	0	-0.6	10	10
ADORA2A	-0.042	0.057	0.23	1	-0.17	10	11
germ cell development	-0.038	0.058	-10000	0	-0.17	8	8
SLC11A2	-0.041	0.059	-10000	0	-0.17	7	7
BHLHE40	-0.04	0.059	-10000	0	-0.17	7	7
HIF1AN	0.017	0.014	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.012	0.075	-10000	0	-0.17	9	9
ETS1	0.029	0.004	-10000	0	-10000	0	0
CITED2	-0.041	0.18	-10000	0	-0.56	16	16
KDR	0.015	0.08	-10000	0	-0.52	3	3
PGK1	-0.041	0.06	-10000	0	-0.17	7	7
SIRT1	0.018	0.012	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF2A/ARNT	0.013	0.094	-10000	0	-0.2	3	3
EPAS1	-0.013	0.037	-10000	0	-0.12	15	15
SP1	0.026	0.004	-10000	0	-10000	0	0
ABCG2	-0.041	0.06	-10000	0	-0.17	7	7
EFNA1	-0.04	0.06	-10000	0	-0.17	7	7
FXN	-0.043	0.058	0.23	1	-0.17	10	11
POU5F1	-0.039	0.059	-10000	0	-0.17	8	8
neuron apoptosis	-0.013	0.092	0.2	3	-10000	0	3
EP300	0.024	0.007	-10000	0	-10000	0	0
EGLN3	0.021	0.014	-10000	0	-10000	0	0
EGLN2	0.023	0.011	-10000	0	-10000	0	0
EGLN1	0.022	0.013	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.048	0.015	-10000	0	-10000	0	0
VHL	0.026	0.004	-10000	0	-10000	0	0
ARNT	0.028	0.004	-10000	0	-10000	0	0
SLC2A1	-0.043	0.057	0.23	1	-0.17	9	10
TWIST1	-0.023	0.042	-10000	0	-0.17	5	5
ELK1	0.028	0	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.002	0.082	-10000	0	-0.18	5	5
VEGFA	-0.042	0.062	-10000	0	-0.18	10	10
CREBBP	0.026	0.004	-10000	0	-10000	0	0

×

Ephrin B reverse 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
EFNB2	0.025	0.006	-10000	0	-10000	0	0
EPHB2	0.025	0.004	-10000	0	-10000	0	0
EFNB1	-0.014	0.013	0.046	1	-10000	0	1
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.018	0.039	0.15	2	-10000	0	2
Ephrin B2/EPHB1-2	0.044	0.016	-10000	0	-0.021	4	4
neuron projection morphogenesis	0.01	0.027	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/Tiam1	0.023	0.034	-10000	0	-10000	0	0
DNM1	0.016	0.013	-10000	0	-10000	0	0
cell-cell signaling	-0.001	0.002	-10000	0	-10000	0	0
MAP2K4	-0.005	0.007	-10000	0	-10000	0	0
YES1	0.016	0.009	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK2	0.022	0.034	-10000	0	-10000	0	0
PI3K	0.039	0.025	-10000	0	-0.22	1	1
mol:GDP	0.022	0.033	-10000	0	-10000	0	0
ITGA2B	0.026	0.003	-10000	0	-10000	0	0
endothelial cell proliferation	0.023	0.017	0.067	1	0	48	49
FYN	0.008	0.037	-10000	0	-10000	0	0
MAP3K7	-0.001	0.002	-10000	0	-10000	0	0
FGR	0.015	0.014	-10000	0	-10000	0	0
TIAM1	0.026	0.004	-10000	0	-10000	0	0
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
RGS3	0.025	0.005	-10000	0	-10000	0	0
cell adhesion	-0.013	0.03	-10000	0	-0.21	1	1
LYN	0.016	0.009	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/Src Family Kinases	0.009	0.005	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2	0.006	0.003	-10000	0	-10000	0	0
SRC	0.016	0.007	-10000	0	-10000	0	0
ITGB3	-0.003	0.04	-10000	0	-0.058	50	50
EPHB1	0.025	0.005	-10000	0	-10000	0	0
EPHB4	0.017	0.015	-10000	0	-0.058	2	2
RAC1	0.017	0.012	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.024	0.017	0.067	1	0	48	49
alphaIIb/beta3 Integrin	0.045	0.011	-10000	0	0	2	2
BLK	0.015	0.014	-10000	0	-10000	0	0
HCK	0.017	0.007	-10000	0	-10000	0	0
regulation of stress fiber formation	-0.021	0.033	-10000	0	-10000	0	0
MAPK8	-0.009	0.008	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/RGS3	0.023	0.034	-10000	0	-10000	0	0
endothelial cell migration	0.05	0.091	0.19	44	-10000	0	44
NCK2	0.026	0.002	-10000	0	-10000	0	0
PTPN13	0.027	0.006	-10000	0	0	2	2
regulation of focal adhesion formation	-0.021	0.033	-10000	0	-10000	0	0
chemotaxis	-0.022	0.033	-10000	0	-10000	0	0
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
Rac1/GTP	0.013	0.031	-10000	0	-10000	0	0
angiogenesis	0.006	0.003	-10000	0	-10000	0	0
LCK	0.017	0.015	-10000	0	-10000	0	0

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.04	0.017	-10000	0	-10000	0	0
PDGFRB	0.026	0.008	-10000	0	-0.058	1	1
SPHK1	0.015	0.01	-10000	0	-10000	0	0
mol:S1P	0.011	0.014	-10000	0	-10000	0	0
S1P1/S1P/Gi	0.007	0.033	-10000	0	-10000	0	0
GNAO1	0.025	0.007	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/PLCgamma1	0.042	0.075	0.2	18	-10000	0	18
PLCG1	-0.003	0.026	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.026	0.008	-10000	0	-0.057	1	1
GNAI2	0.027	0.004	-10000	0	-10000	0	0
GNAI3	0.026	0.003	-10000	0	-10000	0	0
GNAI1	0.017	0.013	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	-0.02	0.011	-10000	0	-0.037	33	33
S1P1/S1P	0.005	0.03	-10000	0	-10000	0	0
negative regulation of cAMP metabolic process	0.007	0.032	-10000	0	-10000	0	0
MAPK3	-0.001	0.03	-10000	0	-10000	0	0
calcium-dependent phospholipase C activity	0	0.001	-10000	0	-10000	0	0
Rac1/GDP	0.013	0.009	-10000	0	0	49	49
RhoA/GDP	0.019	0.002	-10000	0	0	1	1
KDR	0.024	0.007	-10000	0	-10000	0	0
PLCB2	0.013	0.051	0.16	10	-10000	0	10
RAC1	0.017	0.012	-10000	0	-10000	0	0
RhoA/GTP	0.002	0.028	-10000	0	-10000	0	0
receptor internalization	0.005	0.029	-10000	0	-10000	0	0
PTGS2	0.026	0.063	0.28	1	-10000	0	1
Rac1/GTP	-0.005	0.02	-10000	0	-10000	0	0
RHOA	0.026	0.002	-10000	0	-10000	0	0
VEGFA	0.003	0.038	0.057	1	-0.058	40	41
negative regulation of T cell proliferation	0.007	0.032	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	0.025	0.006	-10000	0	-10000	0	0
MAPK1	-0.001	0.031	-10000	0	-10000	0	0
S1P1/S1P/PDGFB-D/PDGFRB	0.014	0.048	0.14	7	-10000	0	7
ABCC1	0.027	0.003	-10000	0	-10000	0	0

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	0.04	0.017	-10000	0	0	16	16
alphaV beta3 Integrin	0.059	0.011	-10000	0	-10000	0	0
PTK2	0	0.062	0.25	2	-0.2	2	4
IGF1R	0.026	0.003	-10000	0	-10000	0	0
PI4KB	0.026	0.004	-10000	0	-10000	0	0
MFGE8	0.026	0.004	-10000	0	-10000	0	0
SRC	0.024	0.007	-10000	0	-10000	0	0
CDKN1B	0.006	0.048	-10000	0	-0.25	5	5
VEGFA	0.002	0.038	-10000	0	-0.058	41	41
ILK	0.01	0.037	-10000	0	-0.25	3	3
ROCK1	0.025	0.005	-10000	0	-10000	0	0
AKT1	-0.014	0.045	0.19	1	-0.24	5	6
PTK2B	-0.028	0.056	0.15	12	-10000	0	12
alphaV/beta3 Integrin/JAM-A	0.057	0.017	-10000	0	-10000	0	0
CBL	0.026	0.002	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.054	0.015	-10000	0	-0.042	1	1
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.064	0.016	-10000	0	-0.027	3	3
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.006	0.043	0.094	1	-0.3	1	2
alphaV/beta3 Integrin/Syndecan-1	0.061	0.014	0.092	8	-10000	0	8
PI4KA	0.025	0.006	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.063	0.023	-10000	0	-10000	0	0
PI4 Kinase	0.036	0.01	-10000	0	0	11	11
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	0.065	0.016	0.092	21	-10000	0	21
RPS6KB1	-0.053	0.026	-10000	0	-10000	0	0
TLN1	0.023	0.008	-10000	0	-10000	0	0
MAPK3	-0.005	0.023	-10000	0	-0.24	1	1
GPR124	0.026	0.004	-10000	0	-10000	0	0
MAPK1	-0.004	0.012	-10000	0	-10000	0	0
PXN	0.026	0.003	-10000	0	-10000	0	0
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	0.059	0.014	-10000	0	-10000	0	0
cell adhesion	0.045	0.024	0.12	1	-0.058	5	6
ANGPTL3	0.021	0.004	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src	0.047	0.025	-10000	0	-0.061	1	1
IGF-1R heterotetramer	0.026	0.003	-10000	0	-10000	0	0
Rac1/GDP	0.013	0.009	-10000	0	-10000	0	0
TGFBR2	0.026	0.002	-10000	0	-10000	0	0
ITGB3	-0.003	0.04	-10000	0	-0.058	50	50
IGF1	0.026	0.004	-10000	0	-10000	0	0
RAC1	0.017	0.012	-10000	0	-10000	0	0
regulation of cell-matrix adhesion	0.057	0.015	-10000	0	-0.043	1	1
apoptosis	0.026	0.002	-10000	0	-10000	0	0
CD47	0.026	0.004	-10000	0	-10000	0	0
alphaV/beta3 Integrin/CD47	0.058	0.013	-10000	0	-10000	0	0
VCL	0.018	0.012	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Del1	0.048	0.025	-10000	0	-10000	0	0
CSF1	0.026	0.003	-10000	0	-10000	0	0
PIK3C2A	0.013	0.023	-10000	0	-0.26	1	1
PI4 Kinase/Pyk2	-0.052	0.035	0.1	5	-10000	0	5
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.069	0.032	-10000	0	-0.035	5	5
FAK1/Vinculin	-0.004	0.053	0.27	2	-10000	0	2
alphaV beta3/Integrin/ppsTEM5	0.058	0.015	-10000	0	-0.043	1	1
RHOA	0.026	0.002	-10000	0	-10000	0	0
VTN	0.026	0.004	-10000	0	-10000	0	0
BCAR1	0.025	0.005	-10000	0	-10000	0	0
FGF2	0.026	0.002	-10000	0	-10000	0	0
F11R	-0.022	0.003	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Lactadherin	0.058	0.013	-10000	0	-10000	0	0
alphaV/beta3 Integrin/TGFBR2	0.059	0.011	-10000	0	-10000	0	0
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.062	0.021	-10000	0	-10000	0	0
HSP90AA1	0.024	0.007	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	0.048	0.026	-10000	0	-0.028	11	11
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.008	0.034	-10000	0	-0.058	31	31
alphaV/beta3 Integrin/Pyk2	0.025	0.064	0.18	12	-10000	0	12
SDC1	0.017	0.026	-10000	0	-0.058	16	16
VAV3	-0.032	0.024	0.17	2	-10000	0	2
PTPN11	0.025	0.004	-10000	0	-10000	0	0
IRS1	0.026	0	-10000	0	-10000	0	0
FAK1/Paxillin	0	0.063	0.23	3	-10000	0	3
cell migration	-0.008	0.049	0.25	2	-0.16	1	3
ITGAV	0.026	0.002	-10000	0	-10000	0	0
PI3K	0.064	0.028	0.15	1	-10000	0	1
SPP1	0	0.039	-10000	0	-0.058	45	45
KDR	0.024	0.007	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.026	0.002	-10000	0	-10000	0	0
COL4A3	0.023	0.014	-10000	0	-0.058	4	4
angiogenesis	-0.001	0.023	-10000	0	-10000	0	0
Rac1/GTP	-0.022	0.028	0.16	2	-10000	0	2
EDIL3	0.021	0.01	-10000	0	-10000	0	0
cell proliferation	0.058	0.011	-10000	0	-10000	0	0

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.01	0.002	0	7	-10000	0	7
GNB1/GNG2	0.047	0.027	-10000	0	-0.028	13	13
regulation of S phase of mitotic cell cycle	0.012	0.019	-10000	0	-0.097	4	4
GNAO1	0.024	0.007	-10000	0	-10000	0	0
HRAS	0.025	0.006	-10000	0	-10000	0	0
SHBG/T-DHT	0.017	0.003	-10000	0	0	4	4
PELP1	0.026	0.004	-10000	0	-10000	0	0
AKT1	-0.01	0.003	0	10	-10000	0	10
MAP2K1	-0.025	0.048	0.14	11	-10000	0	11
T-DHT/AR	0.026	0.01	0.041	49	0	1	50
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.026	0.003	-10000	0	-10000	0	0
GNAI3	0.026	0.003	-10000	0	-10000	0	0
GNAI1	0.017	0.012	-10000	0	-10000	0	0
mol:GDP	-0.013	0.006	-10000	0	-10000	0	0
cell proliferation	-0.007	0.062	0.24	4	-10000	0	4
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
FOS	0.001	0.055	0.21	2	-10000	0	2
mol:Ca2+	-0.001	0.005	-10000	0	-0.028	4	4
MAPK3	-0.01	0.058	0.21	5	-10000	0	5
MAPK1	-0.007	0.083	-10000	0	-0.38	6	6
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
mol:IP3	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	-0.005	0.006	-10000	0	-10000	0	0
GNG2	0.025	0.006	-10000	0	-10000	0	0
potassium channel inhibitor activity	0	0	-10000	0	-10000	0	0
HRAS/GTP	0.046	0.025	-10000	0	-0.039	4	4
actin cytoskeleton reorganization	0.024	0.022	-10000	0	-0.024	6	6
SRC	0.024	0.007	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
PI3K	0.033	0.009	-10000	0	0	10	10
apoptosis	-0.002	0.057	-10000	0	-0.19	4	4
T-DHT/AR/PELP1	0.041	0.011	-10000	0	-10000	0	0
HRAS/GDP	-0.007	0.036	0.094	16	-10000	0	16
CREB1	0.002	0.059	0.2	4	-10000	0	4
RAC1-CDC42/GTP	0.03	0.027	-10000	0	-0.024	6	6
AR	-0.002	0.04	-10000	0	-0.058	49	49
GNB1	0.025	0.006	-10000	0	-10000	0	0
RAF1	-0.019	0.053	0.16	12	-10000	0	12
RAC1-CDC42/GDP	0.022	0.028	-10000	0	-10000	0	0
T-DHT/AR/PELP1/Src	0.051	0.02	-10000	0	-0.029	2	2
MAP2K2	-0.028	0.042	0.14	8	-10000	0	8
T-DHT/AR/PELP1/Src/PI3K	0.012	0.019	-10000	0	-0.098	4	4
GNAZ	0.025	0.006	-10000	0	-10000	0	0
SHBG	0.025	0.004	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.004	0.039	-10000	0	-10000	0	0
mol:T-DHT	0	0	-10000	0	-10000	0	0
RAC1	0.017	0.012	-10000	0	-10000	0	0
GNRH1	-0.011	0.002	0	4	-10000	0	4
Gi family/GTP	0	0.018	0.092	1	-0.096	3	4
CDC42	0.026	0.004	-10000	0	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.025	0.004	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.027	0.011	-9999	-0.059	13	13
MDM2/SUMO1	0.023	0.038	-9999	-0.095	12	12
HDAC4	0.026	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	-0.027	0.011	-9999	-0.059	13	13
SUMO1	0.026	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.006	0.002	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
XPO1	-0.013	0.026	-9999	-0.094	14	14
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.026	0.004	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.026	0	-9999	-10000	0	0
SUMO1/HDAC4	0.026	0.04	-9999	-0.095	14	14
SUMO1/HDAC1	0.025	0.04	-9999	-0.095	14	14
RANGAP1	0.024	0.007	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	0.056	0.027	-9999	-0.028	3	3
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	-0.002	0.029	-9999	-0.093	14	14
Ran/GTP	0.014	0.033	-9999	-0.09	13	13
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.023	0.008	-9999	-10000	0	0
UBE2I	0.026	0.004	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.007	0.032	-9999	-0.094	13	13
NPC	0.015	0	-9999	-10000	0	0
PIAS2	0.025	0.005	-9999	-10000	0	0
PIAS1	0.026	0.004	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

Class I PI3K signaling events

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
ARF5/GTP	-0.016	0.042	0.14	7	-10000	0	7
DAPP1	0.014	0.053	0.14	11	-0.18	2	13
Src family/SYK family/BLNK-LAT/BTK-ITK	0.014	0.071	0.31	2	-0.26	4	6
mol:DAG	0.006	0.063	0.26	4	-10000	0	4
HRAS	0.029	0.011	0.069	1	-0.023	1	2
RAP1A	0.03	0.007	-10000	0	-10000	0	0
ARF5/GDP	0.028	0.041	0.17	2	-0.2	1	3
PLCG2	0.025	0.005	-10000	0	-10000	0	0
PLCG1	0.023	0.008	-10000	0	-10000	0	0
ARF5	0.018	0.012	-10000	0	-10000	0	0
mol:GTP	-0.017	0.049	0.22	4	-10000	0	4
ARF1/GTP	-0.004	0.052	0.22	4	-10000	0	4
RHOA	0.026	0.002	-10000	0	-10000	0	0
YES1	0.025	0.005	-10000	0	-10000	0	0
RAP1A/GTP	-0.02	0.03	0.14	3	-10000	0	3
ADAP1	-0.014	0.045	0.22	3	-10000	0	3
ARAP3	-0.017	0.048	0.21	4	-10000	0	4
INPPL1	0.026	0	-10000	0	-10000	0	0
PREX1	0.024	0.007	-10000	0	-10000	0	0
ARHGEF6	0.026	0.003	-10000	0	-10000	0	0
ARHGEF7	0.025	0.006	-10000	0	-10000	0	0
ARF1	0.025	0.005	-10000	0	-10000	0	0
NRAS	0.028	0.013	-10000	0	-10000	0	0
FYN	0.024	0.007	-10000	0	-10000	0	0
ARF6	0.025	0.006	-10000	0	-10000	0	0
FGR	0.025	0.005	-10000	0	-10000	0	0
mol:Ca2+	0.006	0.045	0.12	16	-10000	0	16
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.026	0.004	-10000	0	-10000	0	0
ZAP70	0.026	0	-10000	0	-10000	0	0
mol:IP3	0.006	0.054	0.14	16	-10000	0	16
LYN	0.026	0.004	-10000	0	-10000	0	0
ARF1/GDP	0.053	0.053	0.2	6	-0.2	1	7
RhoA/GDP	0.045	0.09	0.17	38	-10000	0	38
PDK1/Src/Hsp90	0.044	0.02	-10000	0	-10000	0	0
BLNK	0.018	0.012	-10000	0	-10000	0	0
actin cytoskeleton reorganization	0.062	0.1	0.21	37	-10000	0	37
SRC	0.024	0.007	-10000	0	-10000	0	0
PLEKHA2	-0.025	0.004	-10000	0	-10000	0	0
RAC1	0.017	0.012	-10000	0	-10000	0	0
PTEN	0.016	0.018	-10000	0	-0.039	5	5
HSP90AA1	0.024	0.007	-10000	0	-10000	0	0
ARF6/GTP	-0.022	0.05	0.21	4	-10000	0	4
RhoA/GTP	-0.019	0.05	0.2	5	-10000	0	5
Src family/SYK family/BLNK-LAT	-0.013	0.065	-10000	0	-0.2	11	11
BLK	0.021	0.014	-10000	0	-0.058	4	4
PDPK1	0.025	0.004	-10000	0	-10000	0	0
CYTH1	-0.019	0.052	0.21	5	-10000	0	5
HCK	0.023	0.01	-10000	0	-0.058	1	1
CYTH3	-0.015	0.051	0.23	4	-10000	0	4
CYTH2	-0.018	0.052	0.21	5	-10000	0	5
KRAS	0.027	0.013	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	-0.005	0.047	0.3	1	-0.37	1	2
SGK1	0.001	0.06	0.32	1	-0.39	2	3
INPP5D	0.026	0	-10000	0	-10000	0	0
mol:GDP	0.041	0.055	0.19	7	-0.2	1	8
SOS1	0.026	0	-10000	0	-10000	0	0
SYK	0.025	0.008	-10000	0	-0.058	1	1
ARF6/GDP	-0.004	0.057	0.18	7	-10000	0	7
mol:PI-3-4-5-P3	-0.02	0.029	0.13	3	-10000	0	3
ARAP3/RAP1A/GTP	-0.02	0.03	0.14	3	-10000	0	3
VAV1	0.025	0.005	-10000	0	-10000	0	0
mol:PI-3-4-P2	-0.022	0	-10000	0	-10000	0	0
RAS family/GTP/PI3K Class I	0.041	0.1	0.18	52	-10000	0	52
PLEKHA1	-0.018	0.012	-10000	0	-10000	0	0
Rac1/GDP	0.027	0.043	0.2	3	-0.2	1	4
LAT	0.026	0.004	-10000	0	-10000	0	0
Rac1/GTP	0.032	0.036	-10000	0	-0.17	1	1
ITK	-0.02	0.047	0.2	4	-10000	0	4
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.003	0.072	0.29	4	-10000	0	4
LCK	0.002	0.037	-10000	0	-0.058	40	40
BTK	-0.018	0.052	0.21	5	-10000	0	5

×

S1P3 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
PDGFRB	0.025	0.008	-10000	0	-0.058	1	1
mol:S1P	0	0	-10000	0	-10000	0	0
S1P1/S1P/Gi	0.007	0.016	0.085	1	-0.085	3	4
GNAO1	0.025	0.007	-10000	0	-10000	0	0
S1P/S1P3/G12/G13	0.035	0.025	-10000	0	-0.02	1	1
AKT1	0.012	0.085	-10000	0	-0.33	8	8
AKT3	0.017	0.064	-10000	0	-0.29	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.025	0.008	-10000	0	-0.058	1	1
GNAI2	0.026	0.003	-10000	0	-10000	0	0
GNAI3	0.026	0.003	-10000	0	-10000	0	0
GNAI1	0.017	0.013	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
S1PR3	0.018	0.024	-10000	0	-0.058	13	13
S1PR2	0.023	0.013	-10000	0	-0.058	3	3
EDG1	0	0	-10000	0	-10000	0	0
mol:Ca2+	0.03	0.038	-10000	0	-10000	0	0
MAPK3	0.019	0.038	-10000	0	-10000	0	0
MAPK1	0.021	0.035	-10000	0	-10000	0	0
JAK2	0.01	0.05	0.13	4	-10000	0	4
CXCR4	0.014	0.042	-10000	0	-10000	0	0
FLT1	0.025	0.007	-10000	0	-10000	0	0
RhoA/GDP	0.019	0.002	-10000	0	0	1	1
Rac1/GDP	0.013	0.009	-10000	0	0	49	49
SRC	0.016	0.037	-10000	0	-10000	0	0
S1P/S1P3/Gi	0.03	0.038	-10000	0	-10000	0	0
RAC1	0.017	0.012	-10000	0	-10000	0	0
RhoA/GTP	0.036	0.045	-10000	0	-10000	0	0
VEGFA	0.002	0.038	-10000	0	-0.058	41	41
S1P/S1P2/Gi	0.028	0.038	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0.041	0.017	-10000	0	-10000	0	0
RHOA	0.026	0.002	-10000	0	-10000	0	0
S1P/S1P3/Gq	0.015	0.005	-10000	0	-10000	0	0
GNAQ	0.025	0.005	-10000	0	-10000	0	0
GNAZ	0.025	0.006	-10000	0	-10000	0	0
G12/G13	0.026	0.018	-10000	0	0	49	49
GNA14	0.025	0.005	-10000	0	-10000	0	0
GNA15	0.025	0.006	-10000	0	-10000	0	0
GNA12	0.017	0.012	-10000	0	-10000	0	0
GNA13	0.026	0.002	-10000	0	-10000	0	0
GNA11	0.025	0.006	-10000	0	-10000	0	0
Rac1/GTP	0.017	0.033	-10000	0	-10000	0	0

×

FOXM1 transcription factor network

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
NFATC3	0.028	0.061	-10000	0	-10000	0	0
PLK1	0.024	0.09	-10000	0	-0.73	2	2
BIRC5	0.031	0.015	-10000	0	-10000	0	0
HSPA1B	0.027	0.058	-10000	0	-10000	0	0
MAP2K1	0.028	0.014	-10000	0	-10000	0	0
BRCA2	0.029	0.062	-10000	0	-10000	0	0
FOXM1	0.034	0.063	-10000	0	-10000	0	0
XRCC1	0.036	0.076	0.4	1	-10000	0	1
FOXM1B/p19	0.024	0.059	-10000	0	-10000	0	0
Cyclin D1/CDK4	0.032	0.043	-10000	0	-10000	0	0
CDC2	0.032	0.058	-10000	0	-10000	0	0
TGFA	0.03	0.06	-10000	0	-10000	0	0
SKP2	0.03	0.067	0.45	1	-10000	0	1
CCNE1	0.025	0.007	-10000	0	-10000	0	0
CKS1B	0.032	0.058	-10000	0	-10000	0	0
RB1	0.02	0.084	-10000	0	-10000	0	0
FOXM1C/SP1	0.045	0.062	-10000	0	-10000	0	0
AURKB	0.015	0.12	-10000	0	-0.79	3	3
CENPF	0.031	0.058	-10000	0	-10000	0	0
CDK4	0.021	0.015	-10000	0	-10000	0	0
MYC	0.031	0.051	-10000	0	-10000	0	0
CHEK2	0.03	0.022	-10000	0	-10000	0	0
ONECUT1	0.038	0.056	-10000	0	-10000	0	0
CDKN2A	-0.016	0.03	-10000	0	-0.058	47	47
LAMA4	0.028	0.056	-10000	0	-10000	0	0
FOXM1B/HNF6	0.04	0.058	-10000	0	-10000	0	0
FOS	0.03	0.068	0.4	1	-10000	0	1
SP1	0.026	0.004	-10000	0	-10000	0	0
CDC25B	0.043	0.078	-10000	0	-10000	0	0
response to radiation	0.004	0.004	-10000	0	-10000	0	0
CENPB	0.043	0.078	-10000	0	-10000	0	0
CENPA	0.024	0.058	-10000	0	-10000	0	0
NEK2	0.03	0.056	-10000	0	-10000	0	0
HIST1H2BA	0.025	0.058	-10000	0	-10000	0	0
CCNA2	-0.012	0.05	0.06	15	-0.058	79	94
EP300	0.024	0.007	-10000	0	-10000	0	0
CCNB1/CDK1	0.03	0.06	-10000	0	-10000	0	0
CCNB2	0.026	0.062	-10000	0	-10000	0	0
CCNB1	0.031	0.061	-10000	0	-10000	0	0
ETV5	0.03	0.062	-10000	0	-10000	0	0
ESR1	0.03	0.058	-10000	0	-10000	0	0
CCND1	0.036	0.055	-10000	0	-10000	0	0
GSK3A	0.027	0.013	-10000	0	-10000	0	0
Cyclin A-E1/CDK1-2	0.073	0.031	-10000	0	-10000	0	0
CDK2	-0.001	0.045	0.06	5	-0.058	54	59
G2/M transition of mitotic cell cycle	0.003	0.006	0.031	2	-10000	0	2
FOXM1B/Cbp/p300	0.056	0.066	-10000	0	-10000	0	0
GAS1	0.028	0.061	-10000	0	-10000	0	0
MMP2	0.029	0.066	-10000	0	-10000	0	0
RB1/FOXM1C	0.024	0.049	-10000	0	-10000	0	0
CREBBP	0.026	0.004	-10000	0	-10000	0	0

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.008	0.038	0.13	12	-10000	0	12
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	-0.012	0.041	0.12	1	-0.16	3	4
AP2	0.036	0.01	-10000	0	0	10	10
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.023	0.019	-10000	0	-0.038	2	2
CLTB	0.026	0.003	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.004	0.028	-10000	0	-0.1	9	9
CD4	0.024	0.009	-10000	0	-0.058	1	1
CLTA	0.024	0.007	-10000	0	-10000	0	0
mol:GTP	-0.003	0.002	-10000	0	-0.012	2	2
ARFGAP1	-0.01	0.003	0	15	-10000	0	15
mol:PI-4-5-P2	-0.002	0.014	0.072	5	-10000	0	5
ARF1/GTP	0.029	0.02	-10000	0	-0.082	4	4
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	-0.008	0.018	-10000	0	-0.089	7	7
mol:Choline	-0.002	0.014	0.072	5	-10000	0	5
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.025	0.01	-10000	0	-0.029	4	4
DDEF1	0	0.014	0.072	5	-10000	0	5
ARF1/GDP	0.002	0.012	-10000	0	-0.088	2	2
AP2M1	0.026	0.004	-10000	0	-10000	0	0
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	-0.011	0.009	0.019	2	-10000	0	2
Rac/GTP	0.013	0.01	0.041	1	-0.018	2	3
ARF1/GTP/GGA3/ARF-GAP1	0.029	0.015	-10000	0	-0.03	3	3
ARFIP2	0.022	0.014	-10000	0	-0.044	2	2
COPA	0.026	0.003	-10000	0	-10000	0	0
RAC1	0.017	0.012	-10000	0	-10000	0	0
ARF1/GTP/coatomer protein complex	-0.001	0.039	-10000	0	-0.14	9	9
ARF1/GTP/ARHGAP10	0.016	0.007	-10000	0	-0.02	4	4
GGA3	0.026	0.004	-10000	0	0	3	3
ARF1/GTP/Membrin	0.02	0.013	-10000	0	-10000	0	0
AP2A1	0.025	0.006	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0	0.028	-10000	0	-0.24	1	1
ARF1/GDP/Membrin	0.023	0.013	-10000	0	-10000	0	0
Arfaptin 2/Rac/GDP	0.022	0.019	-10000	0	-0.032	2	2
CYTH2	0.026	0.007	-10000	0	-10000	0	0
ARF1/GTP/GGA3	0.032	0.013	-10000	0	-0.029	4	4
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.013	0.009	-10000	0	0	49	49
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	0.004	0.036	-10000	0	-0.18	2	2
PLD2	-0.002	0.014	0.073	5	-10000	0	5
ARF-GAP1/v-SNARE	-0.01	0.003	0	15	-10000	0	15
PIP5K1A	-0.002	0.014	0.072	5	-10000	0	5
ARF1/GTP/Membrin/GBF1/p115	-0.002	0.036	-10000	0	-0.15	2	2
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.002	0.014	0.072	5	-10000	0	5
KDEL Receptor/Ligand/ARF-GAP1	-0.01	0.003	0	15	-10000	0	15
GOSR2	0.01	0.007	-10000	0	-10000	0	0
USO1	0.01	0.007	-10000	0	-10000	0	0
GBF1	-0.084	0.15	-10000	0	-0.32	42	42
ARF1/GTP/Arfaptin 2	0.034	0.015	-10000	0	-0.04	4	4
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.047	0.017	-10000	0	-10000	0	0

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.025	0.006	-10000	0	-10000	0	0
SPHK1	0.025	0.008	-10000	0	-0.058	1	1
GNAI2	0.026	0.003	-10000	0	-10000	0	0
mol:S1P	0.007	0.002	-10000	0	-10000	0	0
GNAO1	0.024	0.007	-10000	0	-10000	0	0
mol:Sphinganine-1-P	-0.021	0.006	0	10	-0.046	1	11
growth factor activity	0	0	-10000	0	-10000	0	0
S1P/S1P2/G12/G13	0.035	0.03	-10000	0	-0.11	1	1
GNAI3	0.026	0.003	-10000	0	-10000	0	0
G12/G13	0.026	0.018	-10000	0	0	49	49
S1PR3	0.018	0.024	-10000	0	-0.058	13	13
S1PR2	0.023	0.013	-10000	0	-0.058	3	3
EDG1	0	0	-10000	0	-10000	0	0
S1P1/S1P	0.002	0.018	-10000	0	-0.11	4	4
S1PR5	0.023	0.008	-10000	0	-10000	0	0
S1PR4	0.025	0.006	-10000	0	-10000	0	0
GNAI1	0.017	0.012	-10000	0	-10000	0	0
S1P/S1P5/G12	0.024	0.023	-10000	0	-0.11	1	1
S1P/S1P3/Gq	0.009	0.065	-10000	0	-0.37	4	4
S1P/S1P4/Gi	0.028	0.042	0.14	1	-10000	0	1
GNAQ	0.025	0.005	-10000	0	-10000	0	0
GNAZ	0.025	0.006	-10000	0	-10000	0	0
GNA14	0.025	0.005	-10000	0	-10000	0	0
GNA15	0.025	0.006	-10000	0	-10000	0	0
GNA12	0.017	0.012	-10000	0	-10000	0	0
GNA13	0.026	0.002	-10000	0	-10000	0	0
GNA11	0.025	0.006	-10000	0	-10000	0	0
ABCC1	0.026	0.002	-10000	0	-10000	0	0

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.023	0.012	-10000	0	-10000	0	0
PDGF/PDGFRA/CRKL	0.032	0.017	-10000	0	-10000	0	0
positive regulation of JUN kinase activity	0.053	0.027	-10000	0	-10000	0	0
CRKL	0.025	0.006	-10000	0	-10000	0	0
PDGF/PDGFRA/Caveolin-3	0.033	0.015	0.072	1	-10000	0	1
AP1	-0.002	0.063	0.14	23	-10000	0	23
mol:IP3	-0.017	0.013	0.03	4	-10000	0	4
PLCG1	-0.017	0.013	0.03	4	-10000	0	4
PDGF/PDGFRA/alphaV Integrin	0.033	0.015	-10000	0	-10000	0	0
RAPGEF1	0.025	0.006	-10000	0	-10000	0	0
CRK	0.026	0.004	-10000	0	-10000	0	0
mol:Ca2+	-0.017	0.013	0.03	4	-10000	0	4
CAV3	0.021	0.015	-10000	0	-0.058	5	5
CAV1	0.005	0.029	-10000	0	-0.058	22	22
SHC/Grb2/SOS1	0.054	0.028	-10000	0	-10000	0	0
PDGF/PDGFRA/Shf	0.033	0.016	-10000	0	-10000	0	0
FOS	-0.019	0.03	-10000	0	-10000	0	0
JUN	-0.018	0.02	0.024	23	-10000	0	23
oligodendrocyte development	0.033	0.015	-10000	0	-10000	0	0
GRB2	0.025	0.004	-10000	0	-10000	0	0
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
mol:DAG	-0.017	0.013	0.03	4	-10000	0	4
PDGF/PDGFRA	0.023	0.012	-10000	0	-10000	0	0
actin cytoskeleton reorganization	0.03	0.017	-10000	0	-10000	0	0
SRF	-0.021	0.008	-10000	0	-10000	0	0
SHC1	0.023	0.013	-10000	0	-0.058	3	3
PI3K	0.043	0.022	-10000	0	-10000	0	0
PDGF/PDGFRA/Crk/C3G	0.041	0.023	-10000	0	-10000	0	0
JAK1	-0.015	0.014	0.019	12	-10000	0	12
ELK1/SRF	-0.003	0.063	0.14	24	-10000	0	24
SHB	0.024	0.008	-10000	0	-10000	0	0
SHF	0.026	0.004	-10000	0	-10000	0	0
CSNK2A1	0.016	0.023	-10000	0	-0.031	8	8
GO:0007205	-0.012	0.009	-10000	0	-10000	0	0
SOS1	0.026	0	-10000	0	-10000	0	0
Ras protein signal transduction	0.053	0.027	-10000	0	-10000	0	0
PDGF/PDGFRA/SHB	0.03	0.017	-10000	0	-10000	0	0
PDGF/PDGFRA/Caveolin-1	0.025	0.023	-10000	0	-10000	0	0
ITGAV	0.026	0.002	-10000	0	-10000	0	0
ELK1	-0.016	0.012	-10000	0	-10000	0	0
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
PDGF/PDGFRA/Crk	0.033	0.016	-10000	0	-10000	0	0
JAK-STAT cascade	-0.015	0.014	0.019	12	-10000	0	12
cell proliferation	0.033	0.016	-10000	0	-10000	0	0

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.026	0.003	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0.038	0.007	-10000	0	0	5	5
MAP2K4	0.003	0.03	-10000	0	-0.25	1	1
IKBKB	0.026	0.004	-10000	0	-10000	0	0
TNFRSF10B	0.025	0.008	-10000	0	-0.058	1	1
TNFRSF10A	0.026	0.004	-10000	0	-10000	0	0
SMPD1	0.007	0.002	-10000	0	-10000	0	0
IKBKG	0.025	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.024	0.01	-10000	0	-0.058	2	2
TRAIL/TRAILR2	0.038	0.007	-10000	0	0	5	5
TRAIL/TRAILR3	0.041	0.011	-10000	0	0	5	5
TRAIL/TRAILR1	0.037	0.007	-10000	0	0	5	5
TRAIL/TRAILR4	0.038	0.008	-10000	0	0	5	5
TRAIL/TRAILR1/DAP3/GTP	0.048	0.012	-10000	0	-0.02	2	2
IKK complex	-0.049	0.11	-10000	0	-0.22	41	41
RIPK1	0.025	0.005	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.019	0.003	-10000	0	0	3	3
MAPK3	-0.021	0.004	0	4	-10000	0	4
MAP3K1	0.012	0.031	-10000	0	-0.25	1	1
TRAILR4 (trimer)	0.024	0.01	-10000	0	-0.058	2	2
TRADD	0.026	0.003	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.026	0.004	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.013	0.028	-10000	0	-0.2	1	1
CFLAR	0.026	0	-10000	0	-10000	0	0
MAPK1	-0.021	0.005	0	9	-10000	0	9
TRAIL/TRAILR1/FADD/TRADD/RIP	0.071	0.026	-10000	0	-10000	0	0
mol:ceramide	0.007	0.002	-10000	0	-10000	0	0
FADD	0.026	0.002	-10000	0	-10000	0	0
MAPK8	-0.004	0.034	-10000	0	-0.23	2	2
TRAF2	0.025	0.005	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.012	0.031	-10000	0	-0.058	24	24
CHUK	0.018	0.012	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	0.051	0.011	-10000	0	-10000	0	0
DAP3	0.026	0.004	-10000	0	-10000	0	0
CASP10	-0.016	0.016	0.14	1	-10000	0	1
JNK cascade	0.038	0.007	-10000	0	0	5	5
TRAIL (trimer)	0.026	0.003	-10000	0	-10000	0	0
TNFRSF10C	0.012	0.031	-10000	0	-0.058	24	24
TRAIL/TRAILR1/DAP3/GTP/FADD	0.059	0.016	-10000	0	-0.026	3	3
TRAIL/TRAILR2/FADD	0.051	0.011	-10000	0	-10000	0	0
cell death	0.007	0.002	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.013	0.028	-10000	0	-0.2	1	1
TRAILR2 (trimer)	0.025	0.008	-10000	0	-0.058	1	1
CASP8	0.012	0.018	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.071	0.026	-10000	0	-10000	0	0

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
telencephalon oligodendrocyte cell migration	-0.028	0.047	-9999	-10000	0	0
GNAI2	0.026	0.003	-9999	-10000	0	0
S1P/S1P5/G12	0.022	0.017	-9999	0	57	57
mol:GDP	0	0	-9999	-10000	0	0
GNAO1	0.024	0.007	-9999	-10000	0	0
RhoA/GTP	0.029	0.048	-9999	-10000	0	0
negative regulation of cAMP metabolic process	0.025	0.037	-9999	-0.093	3	3
GNAZ	0.025	0.006	-9999	-10000	0	0
GNAI3	0.026	0.003	-9999	-10000	0	0
GNA12	0.017	0.012	-9999	-10000	0	0
S1PR5	0.023	0.008	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
S1P/S1P5/Gi	0.025	0.037	-9999	-0.094	3	3
RhoA/GDP	0.019	0.002	-9999	0	1	1
RHOA	0.026	0.002	-9999	-10000	0	0
GNAI1	0.017	0.012	-9999	-10000	0	0

×

ceramide signaling pathway

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
MAP4K4	0.004	0.058	0.19	1	-0.4	2	3
BAG4	0.026	0.004	-10000	0	-10000	0	0
BAD	-0.006	0.024	-10000	0	-0.14	2	2
NFKBIA	0.025	0.006	-10000	0	-10000	0	0
BIRC3	0.024	0.012	-10000	0	-0.059	3	3
BAX	-0.001	0.04	0.19	4	-0.14	2	6
EnzymeConsortium:3.1.4.12	0.002	0.017	0.065	2	-0.095	2	4
IKBKB	0	0.063	0.2	3	-0.38	2	5
MAP2K2	-0.01	0.044	0.15	7	-0.14	2	9
MAP2K1	-0.014	0.033	0.13	3	-0.14	2	5
SMPD1	-0.001	0.022	0.072	1	-0.095	4	5
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.005	0.063	0.19	1	-0.43	2	3
MAP2K4	-0.011	0.029	0.22	1	-0.14	2	3
protein ubiquitination	-0.002	0.062	0.18	1	-0.4	2	3
EnzymeConsortium:2.7.1.37	-0.015	0.039	0.14	2	-0.15	2	4
response to UV	0	0	0.001	3	-0.002	1	4
RAF1	-0.01	0.03	0.14	2	-0.14	2	4
CRADD	0.025	0.004	-10000	0	-10000	0	0
mol:ceramide	0	0.025	0.085	2	-0.14	2	4
I-kappa-B-alpha/RELA/p50/ubiquitin	0.033	0.009	-10000	0	0	10	10
MADD	0.025	0.004	-10000	0	-10000	0	0
MAP3K1	-0.005	0.03	0.16	2	-0.14	2	4
TRADD	0.026	0.003	-10000	0	-10000	0	0
RELA/p50	0.026	0.003	-10000	0	-10000	0	0
MAPK3	-0.009	0.037	0.11	8	-0.14	2	10
MAPK1	-0.012	0.044	0.11	8	-0.18	3	11
p50/RELA/I-kappa-B-alpha	0.036	0.01	-10000	0	0	10	10
FADD	0.007	0.051	0.19	1	-0.45	1	2
KSR1	-0.005	0.027	0.11	2	-0.14	2	4
MAPK8	-0.012	0.027	0.21	1	-0.14	2	3
TRAF2	0.025	0.005	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	-0.005	0.055	-10000	0	-0.38	2	2
TNF R/SODD	0.036	0.009	-10000	0	0	9	9
TNF	0.025	0.005	-10000	0	-10000	0	0
CYCS	0.016	0.043	0.14	6	-10000	0	6
IKBKG	0	0.062	0.18	3	-0.38	2	5
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.01	0.059	-10000	0	-0.41	2	2
RELA	0.026	0.003	-10000	0	-10000	0	0
RIPK1	0.025	0.005	-10000	0	-10000	0	0
AIFM1	-0.005	0.031	0.12	4	-0.14	1	5
TNF/TNF R/SODD	0.048	0.016	-10000	0	-10000	0	0
TNFRSF1A	0.025	0.005	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.024	0.064	-10000	0	-0.73	1	1
NSMAF	0.007	0.064	0.2	4	-0.39	2	6
response to hydrogen peroxide	0	0	0.001	3	-0.002	1	4
BCL2	0.025	0.005	-10000	0	-10000	0	0

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	-0.017	0.045	-10000	0	-10000	0	0
PLK1	-0.028	0.087	-10000	0	-10000	0	0
CDKN1B	-0.075	0.17	0.25	3	-0.32	41	44
FOXO3	-0.005	0.051	-10000	0	-10000	0	0
KAT2B	0.029	0.003	-10000	0	-10000	0	0
FOXO1/SIRT1	0.008	0.038	-10000	0	-0.18	1	1
CAT	-0.027	0.086	-10000	0	-10000	0	0
CTNNB1	0.026	0.002	-10000	0	-10000	0	0
AKT1	0.027	0.007	-10000	0	-10000	0	0
FOXO1	-0.011	0.05	-10000	0	-0.18	1	1
MAPK10	0.046	0.093	0.18	47	-10000	0	47
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.029	0.072	-10000	0	-10000	0	0
response to oxidative stress	0.003	0.001	-10000	0	-10000	0	0
FOXO3A/SIRT1	-0.002	0.089	0.24	1	-0.35	2	3
XPO1	0.026	0	-10000	0	-10000	0	0
EP300	0.024	0.007	-10000	0	-10000	0	0
BCL2L11	0.023	0.012	-10000	0	-10000	0	0
FOXO1/SKP2	0.005	0.049	-10000	0	-10000	0	0
mol:GDP	0.003	0.001	-10000	0	-10000	0	0
RAN	0.026	0.004	-10000	0	-10000	0	0
GADD45A	-0.044	0.14	-10000	0	-0.52	2	2
YWHAQ	0.026	0.002	-10000	0	-10000	0	0
FOXO1/14-3-3 family	0.022	0.071	-10000	0	-0.26	3	3
MST1	0.029	0.003	-10000	0	-10000	0	0
CSNK1D	0.026	0	-10000	0	-10000	0	0
CSNK1E	0.024	0.007	-10000	0	-10000	0	0
FOXO4/14-3-3 family	0.007	0.047	-10000	0	-0.32	1	1
YWHAB	0.024	0.007	-10000	0	-10000	0	0
MAPK8	0.016	0.068	0.18	21	-10000	0	21
MAPK9	0.047	0.093	0.18	48	-10000	0	48
YWHAG	0.018	0.012	-10000	0	-10000	0	0
YWHAE	0.026	0.004	-10000	0	-10000	0	0
YWHAZ	0.025	0.005	-10000	0	-10000	0	0
SIRT1	0.017	0.013	-10000	0	-0.025	1	1
SOD2	-0.034	0.14	0.23	1	-0.46	10	11
RBL2	0.002	0.084	-10000	0	-0.61	1	1
RAL/GDP	0.026	0.018	-10000	0	-10000	0	0
CHUK	0.02	0.013	-10000	0	-10000	0	0
Ran/GTP	0.02	0.003	-10000	0	-10000	0	0
CSNK1G2	0.025	0.006	-10000	0	-10000	0	0
RAL/GTP	0.026	0.018	-10000	0	-10000	0	0
CSNK1G1	0.026	0.004	-10000	0	-10000	0	0
FASLG	0.021	0.011	-10000	0	-10000	0	0
SKP2	0.026	0.004	-10000	0	-10000	0	0
USP7	0.026	0.004	-10000	0	-10000	0	0
IKBKB	0.028	0.004	-10000	0	-10000	0	0
CCNB1	-0.025	0.089	-10000	0	-10000	0	0
FOXO1-3a-4/beta catenin	0.02	0.075	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.005	0.049	-10000	0	-10000	0	0
CSNK1A1	0.026	0.003	-10000	0	-10000	0	0
SGK1	0.025	0.009	-10000	0	-10000	0	0
CSNK1G3	0.026	0.003	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.036	0.005	-10000	0	-10000	0	0
ZFAND5	0.024	0.068	0.24	1	-10000	0	1
SFN	0.024	0.013	-10000	0	-0.058	3	3
CDK2	0.006	0.045	-10000	0	-0.058	45	45
FOXO3A/14-3-3	0.007	0.047	-10000	0	-0.23	2	2
CREBBP	0.027	0.004	-10000	0	-10000	0	0
FBXO32	-0.019	0.1	0.37	2	-10000	0	2
BCL6	-0.015	0.13	-10000	0	-0.63	5	5
RALB	0.026	0	-10000	0	-10000	0	0
RALA	0.018	0.012	-10000	0	-10000	0	0
YWHAH	0.024	0.007	-10000	0	-10000	0	0

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.037	0.011	-10000	0	0	10	10
FBXW11	0.026	0.003	-10000	0	-10000	0	0
NF kappa B1 p50/c-Rel	-0.025	0.004	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.018	0.051	-10000	0	-0.22	3	3
NFKBIA	0.004	0.034	0.11	10	-0.094	7	17
MAPK14	0.026	0.004	-10000	0	-10000	0	0
NF kappa B1 p105/p50	-0.025	0.004	-10000	0	-10000	0	0
ARRB2	0.009	0.002	-10000	0	-10000	0	0
REL	0.026	0.002	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	-0.025	0.008	-10000	0	-0.046	6	6
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	-0.025	0.005	-10000	0	-10000	0	0
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
NF kappa B1 p50 dimer	-0.021	0.003	-10000	0	-10000	0	0
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
NFKB1	-0.021	0.003	0	3	-10000	0	3
RELA	0.026	0.003	-10000	0	-10000	0	0
positive regulation of anti-apoptosis	0.012	0.024	0.1	1	-0.11	1	2
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.017	0.054	-10000	0	-0.22	4	4
SRC	0.024	0.007	-10000	0	-10000	0	0
PI3K	0.036	0.01	-10000	0	0	10	10
NF kappa B1 p50/RelA	0.012	0.025	0.1	1	-0.11	1	2
IKBKB	0.026	0.004	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.026	0.003	-10000	0	-10000	0	0
SYK	0.025	0.008	-10000	0	-0.058	1	1
I kappa B alpha/PIK3R1	0.015	0.05	-10000	0	-0.23	3	3
cell death	0.017	0.052	-10000	0	-0.21	4	4
NF kappa B1 p105/c-Rel	-0.025	0.004	-10000	0	-10000	0	0
LCK	0.002	0.037	-10000	0	-0.058	40	40
BCL3	0.021	0.019	-10000	0	-0.058	7	7

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.026	0.002	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	0.034	0.035	-9999	-0.23	1	1
Syndecan-3/Neurocan	0.021	0.038	-9999	-0.41	1	1
POMC	0.026	0.003	-9999	-10000	0	0
EGFR	0.007	0.016	-9999	-0.058	4	4
Syndecan-3/EGFR	0.009	0.026	-9999	-0.23	1	1
AGRP	0.024	0.004	-9999	-10000	0	0
NCSTN	0.026	0.003	-9999	-10000	0	0
PSENEN	0.025	0.006	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.026	0.004	-9999	-10000	0	0
APH1A	0.026	0.003	-9999	-10000	0	0
NCAN	0.024	0.007	-9999	-10000	0	0
long-term memory	0.036	0.039	-9999	-0.4	1	1
Syndecan-3/IL8	0.03	0.039	-9999	-0.41	1	1
PSEN1	0.024	0.007	-9999	-10000	0	0
Src/Cortactin	0.036	0.011	-9999	0	12	12
FYN	0.024	0.007	-9999	-10000	0	0
limb bud formation	0.004	0.035	-9999	-0.42	1	1
MC4R	0.017	0.013	-9999	-0.058	1	1
SRC	0.024	0.007	-9999	-10000	0	0
PTN	0.018	0.012	-9999	-10000	0	0
FGFR/FGF/Syndecan-3	0.004	0.035	-9999	-0.42	1	1
neuron projection morphogenesis	0.022	0.077	-9999	-0.23	1	1
Syndecan-3/AgRP	0.022	0.037	-9999	-0.41	1	1
Syndecan-3/AgRP/MC4R	0.026	0.042	-9999	-0.4	1	1
Fyn/Cortactin	0.035	0.011	-9999	0	13	13
SDC3	0.004	0.036	-9999	-0.43	1	1
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	0.029	0.039	-9999	-0.4	1	1
IL8	0.004	0.037	-9999	-0.058	38	38
Syndecan-3/Fyn/Cortactin	0.037	0.04	-9999	-0.4	1	1
Syndecan-3/CASK	0.004	0.034	-9999	-0.4	1	1
alpha-MSH/MC4R	0.027	0.017	-9999	0	43	43
Gamma Secretase	0.063	0.035	-9999	-10000	0	0

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	0.014	0.025	-10000	0	-0.26	1	1
MKNK1	0.025	0.004	-10000	0	-10000	0	0
MAPK14	0.03	0.023	-10000	0	-0.22	1	1
ATF2/c-Jun	-0.004	0.044	-10000	0	-0.16	3	3
MAPK11	0.027	0.024	-10000	0	-0.22	1	1
MITF	0.013	0.025	-10000	0	-0.26	1	1
MAPKAPK5	0.013	0.024	-10000	0	-0.26	1	1
KRT8	0.012	0.024	-10000	0	-0.26	1	1
MAPKAPK3	0.026	0.003	-10000	0	-10000	0	0
MAPKAPK2	0.025	0.005	-10000	0	-10000	0	0
p38alpha-beta/CK2	0.037	0.033	-10000	0	-0.3	1	1
CEBPB	0.013	0.025	-10000	0	-0.26	1	1
SLC9A1	0.012	0.023	-10000	0	-0.26	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	0.014	0.029	0.14	3	-0.25	1	4
p38alpha-beta/MNK1	0.045	0.032	-10000	0	-0.24	1	1
JUN	-0.008	0.042	-10000	0	-0.19	2	2
PPARGC1A	0.013	0.025	-10000	0	-0.26	1	1
USF1	0.013	0.025	-10000	0	-0.26	1	1
RAB5/GDP/GDI1	0.009	0.049	-10000	0	-0.15	4	4
NOS2	0.01	0.053	-10000	0	-0.38	2	2
DDIT3	0.013	0.01	-10000	0	-10000	0	0
RAB5A	0.026	0.002	-10000	0	-10000	0	0
HSPB1	0.064	0.12	0.26	39	-0.22	1	40
p38alpha-beta/HBP1	0.032	0.036	-10000	0	-0.24	1	1
CREB1	-0.004	0.066	-10000	0	-0.2	14	14
RAB5/GDP	0.019	0.002	-10000	0	-10000	0	0
EIF4E	-0.025	0.041	0.2	4	-0.22	1	5
RPS6KA4	0.013	0.025	-10000	0	-0.26	1	1
PLA2G4A	-0.025	0.041	0.2	4	-0.22	1	5
GDI1	0.013	0.025	-10000	0	-0.26	1	1
TP53	-0.012	0.028	-10000	0	-0.31	1	1
RPS6KA5	0.012	0.025	-10000	0	-0.26	1	1
ESR1	0.012	0.024	-10000	0	-0.26	1	1
HBP1	0.018	0.012	-10000	0	-10000	0	0
MEF2C	0.013	0.024	-10000	0	-0.26	1	1
MEF2A	0.013	0.025	-10000	0	-0.26	1	1
EIF4EBP1	-0.003	0.066	-10000	0	-0.2	14	14
KRT19	0.012	0.025	-10000	0	-0.26	1	1
ELK4	0.013	0.025	-10000	0	-0.26	1	1
ATF6	0.013	0.025	-10000	0	-0.26	1	1
ATF1	-0.005	0.065	-10000	0	-0.2	14	14
p38alpha-beta/MAPKAPK2	0.047	0.033	-10000	0	-0.24	1	1
p38alpha-beta/MAPKAPK3	0.048	0.032	-10000	0	-0.24	1	1

×

IL6-mediated signaling events

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
BCL2L1	0.095	0.12	0.38	10	-10000	0	10
CRP	0.081	0.1	0.38	4	-10000	0	4
cell cycle arrest	0.089	0.1	0.35	6	-10000	0	6
TIMP1	0.092	0.092	0.38	3	-10000	0	3
IL6ST	0.027	0.004	-10000	0	-10000	0	0
Rac1/GDP	0.027	0.048	0.27	3	-10000	0	3
AP1	0.068	0.051	-10000	0	-10000	0	0
GAB2	0.026	0.002	-10000	0	-10000	0	0
TNFSF11	0.08	0.098	0.38	3	-10000	0	3
HSP90B1	0.052	0.031	-10000	0	-10000	0	0
GAB1	0.026	0.004	-10000	0	-10000	0	0
MAPK14	0.01	0.04	-10000	0	-0.19	1	1
AKT1	0.023	0.033	0.21	1	-0.28	1	2
FOXO1	0.015	0.036	-10000	0	-0.28	1	1
MAP2K6	0.012	0.032	0.1	13	-0.19	1	14
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.023	0.062	0.31	5	-10000	0	5
MITF	0.013	0.033	0.1	14	-0.19	1	15
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.025	0.006	-10000	0	-10000	0	0
A2M	-0.001	0.13	-10000	0	-1.1	2	2
CEBPB	0.025	0.01	-10000	0	-0.057	1	1
GRB2/SOS1/GAB family/SHP2	0.049	0.041	-10000	0	-10000	0	0
STAT3	0.09	0.11	0.41	3	-10000	0	3
STAT1	0.018	0.015	-10000	0	-10000	0	0
CEBPD	0.082	0.1	0.38	4	-10000	0	4
PIK3CA	0.026	0.004	-10000	0	-10000	0	0
PI3K	0.037	0.01	-10000	0	-10000	0	0
JUN	0.025	0.004	-10000	0	-10000	0	0
PIAS3/MITF	0.068	0.067	0.18	27	-0.18	1	28
MAPK11	0.007	0.036	-10000	0	-0.19	1	1
STAT3 (dimer)/FOXO1	0.017	0.036	-10000	0	-10000	0	0
GRB2/SOS1/GAB family	0.078	0.049	0.16	5	-0.19	1	6
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	0.011	0.026	-10000	0	-0.19	1	1
GRB2	0.026	0.004	-10000	0	-10000	0	0
JAK2	0.023	0.009	-10000	0	-10000	0	0
LBP	0.094	0.1	0.35	9	-10000	0	9
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
JAK1	0.026	0.005	-10000	0	-10000	0	0
MYC	0.089	0.11	0.41	5	-10000	0	5
FGG	0.079	0.098	0.38	3	-10000	0	3
macrophage differentiation	0.089	0.1	0.35	6	-10000	0	6
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0.048	0.043	-10000	0	-10000	0	0
JUNB	0.085	0.11	0.37	9	-10000	0	9
FOS	0.024	0.008	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	0.012	0.021	-10000	0	-0.19	1	1
STAT1/PIAS1	0.045	0.042	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2/PI3K	0.031	0.031	-10000	0	-0.29	1	1
STAT3 (dimer)	0.09	0.1	0.38	4	-10000	0	4
PRKCD	0.11	0.15	0.31	51	-10000	0	51
IL6R	0.026	0.004	-10000	0	-10000	0	0
SOCS3	0.052	0.085	0.32	4	-10000	0	4
gp130 (dimer)/JAK1/JAK1/LMO4	0.053	0.014	-10000	0	-10000	0	0
Rac1/GTP	0.022	0.032	-10000	0	-10000	0	0
HCK	0.023	0.01	-10000	0	-0.058	1	1
MAPKKK cascade	0.056	0.046	-10000	0	-10000	0	0
bone resorption	0.08	0.097	0.38	3	-10000	0	3
IRF1	0.079	0.099	0.38	3	-10000	0	3
mol:GDP	0.012	0.031	0.1	10	-0.18	1	11
SOS1	0.026	0	-10000	0	-10000	0	0
VAV1	0.012	0.031	0.1	11	-0.18	1	12
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	0.017	0.04	0.19	1	-0.34	1	2
PTPN11	0.013	0.066	-10000	0	-0.76	1	1
IL6/IL6RA	0.029	0.02	-10000	0	-10000	0	0
gp130 (dimer)/TYK2/TYK2/LMO4	0.05	0.017	-10000	0	-10000	0	0
gp130 (dimer)/JAK2/JAK2/LMO4	0.046	0.02	-10000	0	-10000	0	0
IL6	0.017	0.018	-10000	0	-0.057	4	4
PIAS3	0.026	0.004	-10000	0	-10000	0	0
PTPRE	0.016	0.012	-10000	0	-0.022	1	1
PIAS1	0.026	0.004	-10000	0	-10000	0	0
RAC1	0.018	0.012	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	0.011	0.014	-10000	0	-10000	0	0
LMO4	0.027	0.005	-10000	0	-10000	0	0
STAT3 (dimer)/PIAS3	0.046	0.048	-10000	0	-10000	0	0
MCL1	0.02	0.044	-10000	0	-10000	0	0

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	0.008	0.03	-10000	0	-0.11	9	9
epithelial cell differentiation	0.051	0.02	-10000	0	-0.026	6	6
CYFIP2	0.026	0.004	-10000	0	-10000	0	0
ENAH	-0.039	0.05	0.4	1	-10000	0	1
EGFR	0.007	0.016	-10000	0	-0.058	4	4
EPHA2	0.024	0.011	-10000	0	-0.058	2	2
MYO6	-0.027	0.029	0.16	3	-10000	0	3
CTNNB1	0.026	0.002	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.037	0.025	-10000	0	-10000	0	0
AQP5	-0.021	0.059	-10000	0	-0.29	6	6
CTNND1	0.026	0.002	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.027	0.028	0.16	3	-10000	0	3
regulation of calcium-dependent cell-cell adhesion	-0.024	0.029	0.16	3	-10000	0	3
EGF	0.026	0.002	-10000	0	-10000	0	0
NCKAP1	0.026	0	-10000	0	-10000	0	0
AQP3	-0.018	0.048	-10000	0	-0.29	4	4
cortical microtubule organization	0.051	0.02	-10000	0	-0.026	6	6
GO:0000145	-0.025	0.026	0.15	3	-10000	0	3
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.056	0.022	-10000	0	-0.026	6	6
MLLT4	0.023	0.008	-10000	0	-10000	0	0
ARF6/GDP	-0.048	0.015	-10000	0	-10000	0	0
ARF6	0.025	0.006	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.06	0.023	-10000	0	-0.028	4	4
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.013	0.022	0.15	1	-0.18	1	2
PVRL2	0.025	0.006	-10000	0	-10000	0	0
ZYX	-0.02	0.026	0.16	2	-10000	0	2
ARF6/GTP	0.061	0.033	-10000	0	-10000	0	0
CDH1	0.025	0.006	-10000	0	-10000	0	0
EGFR/EGFR/EGF/EGF	0.016	0.026	-10000	0	-10000	0	0
RhoA/GDP	0.052	0.022	-10000	0	-10000	0	0
actin cytoskeleton organization	-0.021	0.025	0.15	2	-10000	0	2
IGF-1R heterotetramer	0.026	0.003	-10000	0	-10000	0	0
GIT1	0.026	0.004	-10000	0	-10000	0	0
IGF1R	0.026	0.003	-10000	0	-10000	0	0
IGF1	0.026	0.004	-10000	0	-10000	0	0
DIAPH1	-0.1	0.24	-10000	0	-0.48	40	40
Wnt receptor signaling pathway	-0.051	0.02	0.026	6	-10000	0	6
RHOA	0.026	0.002	-10000	0	-10000	0	0
RhoA/GTP	-0.048	0.015	-10000	0	-10000	0	0
CTNNA1	0.026	0.004	-10000	0	-10000	0	0
VCL	-0.021	0.026	0.15	2	-10000	0	2
EFNA1	0.025	0.004	-10000	0	-10000	0	0
LPP	-0.031	0.025	0.15	2	-10000	0	2
Ephrin A1/EPHA2	0.043	0.023	-10000	0	-10000	0	0
SEC6/SEC8	-0.031	0.023	-10000	0	-10000	0	0
MGAT3	-0.024	0.029	0.16	3	-10000	0	3
HGF/MET	0.026	0.029	-10000	0	-10000	0	0
HGF	0.018	0.012	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.008	0.031	-10000	0	-0.11	9	9
actin cable formation	-0.025	0.065	0.24	3	-0.24	1	4
KIAA1543	-0.027	0.026	0.15	3	-10000	0	3
KIFC3	-0.03	0.017	0.16	1	-10000	0	1
NCK1	0.026	0.004	-10000	0	-10000	0	0
EXOC3	0.025	0.005	-10000	0	-10000	0	0
ACTN1	-0.027	0.024	0.16	2	-10000	0	2
NCK1/GIT1	0.037	0.008	-10000	0	0	6	6
mol:GDP	0.051	0.02	-10000	0	-0.026	6	6
EXOC4	0.018	0.012	-10000	0	-10000	0	0
STX4	-0.029	0.023	0.16	2	-10000	0	2
PIP5K1C	-0.027	0.029	0.16	3	-10000	0	3
LIMA1	0.015	0.027	-10000	0	-0.058	17	17
ABI1	0.018	0.012	-10000	0	-10000	0	0
ROCK1	-0.038	0.057	0.43	1	-10000	0	1
adherens junction assembly	-0.021	0.041	0.24	1	-0.2	1	2
IGF-1R heterotetramer/IGF1	0.044	0.023	-10000	0	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.033	0.014	-10000	0	0	22	22
MET	0.016	0.013	-10000	0	-10000	0	0
PLEKHA7	-0.028	0.028	0.16	3	-10000	0	3
mol:GTP	0.058	0.022	-10000	0	-0.028	4	4
establishment of epithelial cell apical/basal polarity	0.02	0.1	0.3	5	-10000	0	5
cortical actin cytoskeleton stabilization	0.008	0.03	-10000	0	-0.11	9	9
regulation of cell-cell adhesion	-0.021	0.025	0.15	2	-10000	0	2
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.008	0.031	-10000	0	-0.11	9	9

×

Insulin Pathway

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
CBL/APS/CAP	0.025	0.033	-10000	0	-10000	0	0
TC10/GTP	0.022	0.033	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	0.059	0.028	-10000	0	-0.03	7	7
HRAS	0.025	0.006	-10000	0	-10000	0	0
APS homodimer	0.018	0.012	-10000	0	-10000	0	0
GRB14	0.026	0.003	-10000	0	-10000	0	0
FOXO3	-0.051	0.21	-10000	0	-0.65	16	16
AKT1	-0.022	0.059	0.19	4	-10000	0	4
INSR	0.028	0.011	0.064	9	-10000	0	9
Insulin Receptor/Insulin	0.039	0.022	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.017	0.013	-10000	0	-10000	0	0
SORBS1	0.018	0.012	-10000	0	-10000	0	0
CRK	0.026	0.004	-10000	0	-10000	0	0
PTPN1	-0.018	0.02	0.14	2	-10000	0	2
CAV1	-0.015	0.035	0.18	3	-10000	0	3
CBL/APS/CAP/Crk-II/C3G	0.037	0.045	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1/NCK2	0.06	0.028	-10000	0	-0.03	7	7
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.045	0.026	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.026	0.036	0.17	8	-10000	0	8
RPS6KB1	-0.027	0.055	0.14	11	-10000	0	11
PARD6A	0.026	0.003	-10000	0	-10000	0	0
CBL	0.026	0.002	-10000	0	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.014	0.011	-10000	0	-10000	0	0
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.036	0.047	0.13	7	-10000	0	7
HRAS/GTP	-0.039	0.022	0.031	8	-10000	0	8
Insulin Receptor	0.028	0.011	0.064	9	-10000	0	9
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.067	0.034	-10000	0	-10000	0	0
PRKCI	0.026	0.032	-10000	0	-0.34	1	1
Insulin Receptor/Insulin/GRB14/PDK1	-0.034	0.025	0.053	8	-10000	0	8
SHC1	0.023	0.013	-10000	0	-0.058	3	3
negative regulation of MAPKKK cascade	0.02	0.041	-10000	0	-10000	0	0
PI3K	0.056	0.03	-10000	0	-10000	0	0
NCK2	0.026	0.002	-10000	0	-10000	0	0
RHOQ	0.026	0	-10000	0	-10000	0	0
mol:H2O2	-0.003	0.002	-10000	0	-10000	0	0
HRAS/GDP	0.018	0.004	-10000	0	-10000	0	0
AKT2	-0.028	0.053	0.31	1	-10000	0	1
PRKCZ	-0.049	0.14	-10000	0	-0.32	32	32
SH2B2	0.018	0.012	-10000	0	-10000	0	0
SHC/SHIP	-0.018	0.047	0.17	6	-10000	0	6
F2RL2	0.006	0.035	-10000	0	-0.058	34	34
TRIP10	0.025	0.005	-10000	0	-10000	0	0
Insulin Receptor/Insulin/Shc	0.044	0.023	0.1	9	-0.022	6	15
TC10/GTP/CIP4/Exocyst	0.034	0.007	-10000	0	0	6	6
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.067	0.034	-10000	0	-10000	0	0
RAPGEF1	0.025	0.006	-10000	0	-10000	0	0
RASA1	0.026	0.004	-10000	0	-10000	0	0
NCK1	0.026	0.004	-10000	0	-10000	0	0
CBL/APS/CAP/Crk-II	0.034	0.038	-10000	0	-0.028	17	17
TC10/GDP	0.019	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.037	0.035	-10000	0	-0.03	5	5
INPP5D	-0.015	0.043	0.17	6	-10000	0	6
SOS1	0.026	0	-10000	0	-10000	0	0
SGK1	-0.062	0.21	-10000	0	-0.67	16	16
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.025	0.004	-10000	0	-10000	0	0
IRS1	0.026	0	-10000	0	-10000	0	0
p62DOK/RasGAP	0.02	0.041	-10000	0	-10000	0	0
INS	-0.012	0.026	0.08	4	-10000	0	4
mol:PI-3-4-P2	-0.015	0.043	0.17	6	-10000	0	6
GRB2	0.025	0.004	-10000	0	-10000	0	0
EIF4EBP1	-0.03	0.056	0.15	6	-10000	0	6
PTPRA	0.024	0.008	-10000	0	-10000	0	0
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
TC10/GTP/CIP4	0.034	0.007	-10000	0	0	6	6
PDPK1	0.025	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.013	0.027	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.045	0.022	0.1	9	-0.022	7	16
Insulin Receptor/Insulin/IRS3	0.036	0.019	0.098	9	-10000	0	9
Par3/Par6	0.061	0.021	-10000	0	-10000	0	0

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.022	0.008	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP1	-0.013	0.005	-10000	0	-10000	0	0
mol:DAG	-0.025	0.022	0.18	1	-10000	0	1
VEGFR1 homodimer/NRP1/VEGFR 121	0.021	0.02	-10000	0	-10000	0	0
CaM/Ca2+	-0.029	0.023	0.18	1	-10000	0	1
HIF1A	0.027	0.007	-10000	0	-10000	0	0
GAB1	0.026	0.004	-10000	0	-10000	0	0
AKT1	-0.027	0.034	0.13	5	-10000	0	5
PLCG1	-0.025	0.022	0.18	1	-10000	0	1
NOS3	-0.01	0.04	0.22	1	-0.2	3	4
CBL	0.026	0.002	-10000	0	-10000	0	0
mol:NO	0.008	0.055	0.22	1	-0.22	1	2
FLT1	-0.017	0.007	-10000	0	-10000	0	0
PGF	0.011	0.031	-10000	0	-0.058	23	23
VEGFR1 homodimer/NRP2/VEGFR121	0.035	0.027	-10000	0	-10000	0	0
CALM1	0.024	0.007	-10000	0	-10000	0	0
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
eNOS/Hsp90	0.011	0.075	0.2	4	-0.21	1	5
endothelial cell proliferation	-0.026	0.034	0.13	1	-10000	0	1
mol:Ca2+	-0.025	0.022	0.18	1	-10000	0	1
MAPK3	-0.033	0.022	0.15	1	-10000	0	1
MAPK1	-0.032	0.023	0.15	1	-10000	0	1
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
PLGF homodimer	0.011	0.031	-10000	0	-0.058	23	23
PRKACA	0.025	0.006	-10000	0	-10000	0	0
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	0.005	0.029	-10000	0	-0.058	22	22
VEGFA homodimer	0.002	0.038	-10000	0	-0.058	41	41
VEGFR1 homodimer/VEGFA homodimer	0.024	0.019	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	-0.037	0.023	0.14	1	-10000	0	1
PI3K	0.043	0.036	0.16	1	-10000	0	1
PRKCA	-0.028	0.022	0.17	1	-10000	0	1
PRKCB	-0.013	0.018	-10000	0	-10000	0	0
VEGFR1 homodimer/PLGF homodimer	0.025	0.012	-10000	0	-10000	0	0
VEGFA	0.002	0.038	-10000	0	-0.058	41	41
VEGFB	0.026	0.002	-10000	0	-10000	0	0
mol:IP3	-0.025	0.022	0.18	1	-10000	0	1
RASA1	-0.026	0.018	0.18	1	-10000	0	1
NRP2	0.026	0	-10000	0	-10000	0	0
VEGFR1 homodimer	-0.017	0.007	-10000	0	-10000	0	0
VEGFB homodimer	0.026	0.002	-10000	0	-10000	0	0
NCK1	0.026	0.004	-10000	0	-10000	0	0
eNOS/Caveolin-1	-0.009	0.051	0.2	1	-0.21	2	3
PTPN11	0.025	0.004	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.041	0.034	-10000	0	-10000	0	0
mol:L-citrulline	0.008	0.055	0.22	1	-0.22	1	2
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.046	0.037	0.16	1	-10000	0	1
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.034	0.027	-10000	0	-10000	0	0
CD2AP	0.025	0.005	-10000	0	-10000	0	0
PI3K/GAB1	0.05	0.042	0.16	1	-10000	0	1
PDPK1	-0.032	0.035	0.15	5	-10000	0	5
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.034	0.028	-10000	0	-10000	0	0
mol:NADP	0.008	0.055	0.22	1	-0.22	1	2
HSP90AA1	0.024	0.007	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.043	0.035	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP2	0.022	0.008	-10000	0	-10000	0	0

×

ErbB2/ErbB3 signaling events

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
USP8	-0.016	0.008	0.021	3	-10000	0	3
RAS family/GTP	0.019	0.058	-10000	0	-10000	0	0
NFATC4	-0.023	0.055	0.34	2	-10000	0	2
ERBB2IP	0.026	0.006	-10000	0	-0.023	1	1
HSP90 (dimer)	0.024	0.007	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.039	0.028	0.14	2	-10000	0	2
JUN	-0.004	0.046	0.16	3	-10000	0	3
HRAS	0.025	0.006	-10000	0	-10000	0	0
DOCK7	-0.039	0.036	0.12	2	-10000	0	2
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.033	0.033	0.17	1	-10000	0	1
AKT1	-0.01	0.007	0.011	11	-10000	0	11
BAD	-0.017	0.006	0.019	1	-10000	0	1
MAPK10	0.003	0.059	0.17	4	-10000	0	4
mol:GTP	0	0	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.041	0.03	0.15	2	-10000	0	2
RAF1	-0.025	0.061	0.22	5	-10000	0	5
ErbB2/ErbB3/neuregulin 2	-0.027	0.019	-10000	0	-10000	0	0
STAT3	0.028	0.014	-10000	0	-10000	0	0
cell migration	-0.007	0.06	0.37	2	-10000	0	2
mol:PI-3-4-5-P3	-0.001	0.001	-10000	0	-10000	0	0
cell proliferation	0.007	0.079	0.4	2	-10000	0	2
FOS	0.006	0.067	0.28	4	-10000	0	4
NRAS	0.026	0.003	-10000	0	-10000	0	0
mol:Ca2+	-0.039	0.028	0.14	2	-10000	0	2
MAPK3	0.007	0.073	0.4	2	-10000	0	2
MAPK1	-0.002	0.089	0.4	2	-0.34	1	3
JAK2	-0.036	0.036	0.12	2	-10000	0	2
NF2	0.005	0.003	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0.003	0.014	0.094	3	-10000	0	3
NRG1	0.022	0.01	-10000	0	-0.021	1	1
GRB2/SOS1	0.038	0.006	-10000	0	0	4	4
MAPK8	-0.025	0.066	-10000	0	-0.17	22	22
MAPK9	0.004	0.06	0.17	5	-10000	0	5
ERBB2	-0.027	0.004	0	3	-10000	0	3
ERBB3	0.023	0.008	-10000	0	-10000	0	0
SHC1	0.024	0.013	-10000	0	-0.058	3	3
RAC1	0.017	0.012	-10000	0	-10000	0	0
apoptosis	0.01	0.018	-10000	0	-0.21	1	1
STAT3 (dimer)	0.028	0.014	-10000	0	-10000	0	0
RNF41	-0.021	0.009	-10000	0	-10000	0	0
FRAP1	-0.008	0.004	0.011	3	-10000	0	3
RAC1-CDC42/GTP	-0.029	0.025	-10000	0	-10000	0	0
ErbB2/ErbB2/HSP90 (dimer)	-0.027	0.01	0.027	1	-10000	0	1
CHRNA1	0.01	0.066	0.32	3	-10000	0	3
myelination	-0.03	0.06	0.31	3	-10000	0	3
PPP3CB	-0.028	0.032	0.12	2	-10000	0	2
KRAS	0.025	0.006	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0.01	0.045	-10000	0	-10000	0	0
NRG2	0.026	0.004	-10000	0	-10000	0	0
mol:GDP	0.003	0.014	0.094	3	-10000	0	3
SOS1	0.026	0	-10000	0	-10000	0	0
MAP2K2	-0.025	0.068	0.25	5	-10000	0	5
SRC	0.024	0.007	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.001	-10000	0	-10000	0	0
PTPN11	-0.04	0.036	0.12	2	-10000	0	2
MAP2K1	-0.002	0.099	0.47	1	-0.55	2	3
heart morphogenesis	-0.039	0.028	0.14	2	-10000	0	2
RAS family/GDP	0.023	0.061	-10000	0	-10000	0	0
GRB2	0.025	0.004	-10000	0	-10000	0	0
PRKACA	0.013	0.005	-10000	0	-10000	0	0
CHRNE	0	0.012	0.047	3	-10000	0	3
HSP90AA1	0.024	0.007	-10000	0	-10000	0	0
activation of caspase activity	0.01	0.007	-10000	0	-0.011	11	11
nervous system development	-0.039	0.028	0.14	2	-10000	0	2
CDC42	0.026	0.004	-10000	0	-10000	0	0

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.024	0.007	-10000	0	-10000	0	0
HSPA8	0.026	0.002	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	0.046	0.03	-10000	0	-0.085	2	2
AKT1	0.025	0.007	-10000	0	-10000	0	0
GSC	-0.023	0.11	-10000	0	-0.41	10	10
NKX2-5	0	0	-10000	0	-10000	0	0
muscle cell differentiation	-0.038	0.056	0.22	6	-10000	0	6
SMAD2-3/SMAD4/SP1	0.07	0.029	-10000	0	-10000	0	0
SMAD4	0.006	0.032	-10000	0	-0.077	1	1
CBFB	0.026	0.003	-10000	0	-10000	0	0
SAP18	0.024	0.007	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.048	0.017	-10000	0	-10000	0	0
SMAD3/SMAD4/VDR	0.065	0.045	-10000	0	-10000	0	0
MYC	0.021	0.016	-10000	0	-0.059	5	5
CDKN2B	-0.2	0.18	-10000	0	-0.44	12	12
AP1	0.015	0.032	0.14	3	-10000	0	3
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	-0.001	0.06	-10000	0	-0.26	4	4
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.012	0.055	0.13	1	-0.28	4	5
SP3	0.026	0.002	-10000	0	-10000	0	0
CREB1	0.026	0	-10000	0	-10000	0	0
FOXH1	0.025	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/GR	0.05	0.027	-10000	0	-0.084	1	1
GATA3	-0.007	0.034	-10000	0	-0.05	50	50
SKI/SIN3/HDAC complex/NCoR1	0	0.051	-10000	0	-0.21	4	4
MEF2C/TIF2	-0.022	0.048	0.24	4	-10000	0	4
endothelial cell migration	-0.013	0.018	-10000	0	-10000	0	0
MAX	0.024	0.007	-10000	0	-10000	0	0
RBBP7	0.026	0	-10000	0	-10000	0	0
RBBP4	0.025	0.004	-10000	0	-10000	0	0
RUNX2	0.024	0.011	-10000	0	-0.058	2	2
RUNX3	0.024	0.011	-10000	0	-0.058	2	2
RUNX1	0.021	0.02	-10000	0	-0.058	8	8
CTBP1	0.026	0	-10000	0	-10000	0	0
NR3C1	0.026	0.003	-10000	0	-10000	0	0
VDR	0.023	0.015	-10000	0	-0.058	4	4
CDKN1A	0.003	0.05	0.34	1	-0.38	1	2
KAT2B	0.026	0.002	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	0.05	0.017	-10000	0	-10000	0	0
DCP1A	0.026	0.002	-10000	0	-10000	0	0
SKI	0.025	0.006	-10000	0	-10000	0	0
SERPINE1	0.014	0.018	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF2	0.051	0.025	-10000	0	-0.073	2	2
SMAD3/SMAD4/ATF3	0.051	0.023	-10000	0	-10000	0	0
SAP30	0.025	0.005	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.046	0.018	-10000	0	-10000	0	0
JUN	-0.018	0.03	0.14	5	-10000	0	5
SMAD3/SMAD4/IRF7	0.05	0.028	-10000	0	-0.084	1	1
TFE3	0.023	0.015	-10000	0	-0.033	10	10
COL1A2	0.011	0.012	-10000	0	-10000	0	0
mesenchymal cell differentiation	-0.05	0.027	0.073	2	-10000	0	2
DLX1	0.024	0.007	-10000	0	-10000	0	0
TCF3	0.025	0.006	-10000	0	-10000	0	0
FOS	0.023	0.015	0.077	1	-10000	0	1
SMAD3/SMAD4/Max	0.05	0.027	-10000	0	-0.084	1	1
Cbp/p300/SNIP1	0.046	0.018	-10000	0	-10000	0	0
ZBTB17	0.025	0.004	-10000	0	-10000	0	0
LAMC1	-0.026	0.032	0.14	4	-10000	0	4
TGIF2/HDAC complex/SMAD3/SMAD4	0.047	0.029	-10000	0	-0.073	2	2
IRF7	0.023	0.012	-10000	0	-0.048	3	3
ESR1	0.013	0.021	-10000	0	-0.045	2	2
HNF4A	0.02	0.007	-10000	0	-10000	0	0
MEF2C	-0.015	0.054	0.21	7	-10000	0	7
SMAD2-3/SMAD4	0.052	0.026	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.047	0.017	-10000	0	-10000	0	0
IGHV3OR16-13	0.004	0.005	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.023	0.01	-10000	0	-0.058	1	1
CREBBP	0.026	0.004	-10000	0	-10000	0	0
SKIL	0.026	0.003	-10000	0	-10000	0	0
HDAC1	0.025	0.004	-10000	0	-10000	0	0
HDAC2	0.024	0.008	-10000	0	-10000	0	0
SNIP1	0.025	0.004	-10000	0	-10000	0	0
GCN5L2	0	0	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.053	0.03	-10000	0	-0.092	3	3
MSG1/HSC70	0.039	0.004	-10000	0	-10000	0	0
SMAD2	0.026	0.005	-10000	0	-10000	0	0
SMAD3	0.006	0.032	-10000	0	-0.076	1	1
SMAD3/E2F4-5/DP1/p107/SMAD4	0.01	0.029	-10000	0	-0.2	1	1
SMAD2/SMAD2/SMAD4	-0.002	0.035	0.15	2	-0.16	3	5
NCOR1	0.026	0.002	-10000	0	-10000	0	0
NCOA2	0.025	0.004	-10000	0	-10000	0	0
NCOA1	0.026	0.003	-10000	0	-10000	0	0
MYOD/E2A	0.034	0.01	-10000	0	0	10	10
SMAD2-3/SMAD4/SP1/MIZ-1	0.079	0.033	-10000	0	-10000	0	0
IFNB1	-0.019	0.032	0.14	4	-10000	0	4
SMAD3/SMAD4/MEF2C	0.037	0.039	0.19	4	-10000	0	4
CITED1	0.024	0.012	-10000	0	-0.058	3	3
SMAD2-3/SMAD4/ARC105	0.063	0.032	-10000	0	-10000	0	0
RBL1	0.024	0.007	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.005	0.033	-10000	0	-10000	0	0
RUNX1-3/PEBPB2	0.05	0.015	0.092	1	-10000	0	1
SMAD7	0.008	0.042	-10000	0	-10000	0	0
MYC/MIZ-1	0.036	0.011	-10000	0	-10000	0	0
SMAD3/SMAD4	-0.001	0.05	-10000	0	-0.25	1	1
IL10	-0.034	0.04	0.14	5	-10000	0	5
PIASy/HDAC complex	0.025	0.006	-10000	0	-10000	0	0
PIAS3	0.026	0.004	-10000	0	-10000	0	0
CDK2	-0.017	0.041	-10000	0	-0.058	73	73
IL5	-0.033	0.038	0.14	5	-0.12	1	6
CDK4	0.02	0.014	-10000	0	-0.058	2	2
PIAS4	0.025	0.006	-10000	0	-10000	0	0
ATF3	0.025	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4/SP1	0.054	0.03	-10000	0	-0.097	1	1
FOXG1	0.024	0.007	-10000	0	-10000	0	0
FOXO3	-0.018	0.008	-10000	0	-10000	0	0
FOXO1	-0.019	0.007	-10000	0	-10000	0	0
FOXO4	-0.019	0.006	-10000	0	-10000	0	0
heart looping	-0.015	0.053	0.21	7	-10000	0	7
CEBPB	0.023	0.01	-10000	0	-0.058	1	1
SMAD3/SMAD4/DLX1	0.047	0.028	-10000	0	-0.073	2	2
MYOD1	0.02	0.012	-10000	0	-0.058	3	3
SMAD3/SMAD4/HNF4	0.041	0.032	-10000	0	-0.073	2	2
SMAD3/SMAD4/GATA3	0.038	0.047	0.13	1	-0.079	10	11
SnoN/SIN3/HDAC complex/NCoR1	0.026	0.003	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.072	0.034	-10000	0	-10000	0	0
SMAD3/SMAD4/SP1-3	0.07	0.029	-10000	0	-0.09	1	1
MED15	0.025	0.006	-10000	0	-10000	0	0
SP1	0.019	0.019	-10000	0	-10000	0	0
SIN3B	0.025	0.005	-10000	0	-10000	0	0
SIN3A	0.026	0.004	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.048	0.018	-10000	0	-10000	0	0
ITGB5	-0.026	0.046	0.17	6	-10000	0	6
TGIF/SIN3/HDAC complex/CtBP	0.001	0.056	-10000	0	-0.21	6	6
SMAD3/SMAD4/AR	0.055	0.033	0.13	1	-0.075	2	3
AR	-0.002	0.04	-10000	0	-0.058	49	49
negative regulation of cell growth	0.008	0.036	-10000	0	-0.21	3	3
SMAD3/SMAD4/MYOD	0.044	0.032	-10000	0	-0.084	1	1
E2F5	0.025	0.004	-10000	0	-10000	0	0
E2F4	0.026	0.003	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.063	0.038	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4	0.002	0.035	0.14	1	-0.23	1	2
TFDP1	0.025	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.048	0.038	0.2	2	-10000	0	2
SMAD3/SMAD4/RUNX2	0.05	0.027	-10000	0	-0.073	2	2
TGIF2	0.023	0.01	-10000	0	-0.058	1	1
TGIF1	0.019	0.022	-10000	0	-0.058	10	10
ATF2	0.026	0	-10000	0	-10000	0	0

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.025	0.005	-9999	-10000	0	0
SVIL	0.017	0.014	-9999	-0.058	1	1
ZNF318	0.026	0.004	-9999	-10000	0	0
JMJD2C	0	0.001	-9999	-10000	0	0
T-DHT/AR/Ubc9	0.042	0.011	-9999	-10000	0	0
CARM1	0.025	0.006	-9999	-10000	0	0
PRDX1	0.025	0.005	-9999	-10000	0	0
PELP1	0.026	0.004	-9999	-10000	0	0
CTNNB1	0.026	0.002	-9999	-10000	0	0
AKT1	0.024	0.007	-9999	-10000	0	0
PTK2B	0.026	0.004	-9999	-10000	0	0
MED1	0.026	0	-9999	-10000	0	0
MAK	0.013	0.03	-9999	-0.058	21	21
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	0.018	0.012	-9999	-10000	0	0
GSN	0.025	0.006	-9999	-10000	0	0
NCOA2	0.025	0.004	-9999	-10000	0	0
NCOA6	0.024	0.007	-9999	-10000	0	0
DNA-PK	0.047	0.017	-9999	-10000	0	0
NCOA4	0.018	0.012	-9999	-10000	0	0
PIAS3	0.026	0.004	-9999	-10000	0	0
cell proliferation	-0.001	0.072	-9999	-0.42	4	4
XRCC5	0.026	0	-9999	-10000	0	0
UBE3A	0.026	0.004	-9999	-10000	0	0
T-DHT/AR/SNURF	0.041	0.012	-9999	-10000	0	0
FHL2	0.004	0.034	-9999	-0.25	2	2
RANBP9	0.026	0.004	-9999	-10000	0	0
JMJD1A	0.002	0.001	-9999	-10000	0	0
CDK6	0.013	0.019	-9999	-0.058	6	6
TGFB1I1	-0.012	0.042	-9999	-0.058	65	65
T-DHT/AR/CyclinD1	0.043	0.01	-9999	-10000	0	0
XRCC6	0.024	0.007	-9999	-10000	0	0
T-DHT/AR	0.031	0.023	-9999	-0.042	1	1
CTDSP1	0.026	0	-9999	-10000	0	0
CTDSP2	0.022	0.01	-9999	-10000	0	0
BRCA1	0.025	0.007	-9999	-0.058	1	1
TCF4	0.025	0.005	-9999	-10000	0	0
CDKN2A	-0.016	0.03	-9999	-0.058	47	47
SRF	0.027	0.004	-9999	-10000	0	0
NKX3-1	-0.008	0.01	-9999	-10000	0	0
KLK3	0.016	0.037	-9999	-10000	0	0
TMF1	0.026	0.002	-9999	-10000	0	0
HNRNPA1	0.025	0.005	-9999	-10000	0	0
AOF2	0	0	-9999	-10000	0	0
APPL1	-0.02	0.006	-9999	-10000	0	0
T-DHT/AR/Caspase 8	0.043	0.01	-9999	-10000	0	0
AR	-0.002	0.04	-9999	-0.058	49	49
UBA3	0.026	0.002	-9999	-10000	0	0
PATZ1	0.024	0.007	-9999	-10000	0	0
PAWR	0.025	0.006	-9999	-10000	0	0
PRKDC	0.026	0.004	-9999	-10000	0	0
PA2G4	0.025	0.006	-9999	-10000	0	0
UBE2I	0.026	0.004	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	0.039	0.013	-9999	-0.032	2	2
RPS6KA3	0.026	0	-9999	-10000	0	0
T-DHT/AR/ARA70	0.03	0.021	-9999	-0.039	1	1
LATS2	0.024	0.007	-9999	-10000	0	0
T-DHT/AR/PRX1	0.039	0.012	-9999	-10000	0	0
Cyclin D3/CDK11 p58	0.019	0.003	-9999	0	3	3
VAV3	0.026	0.003	-9999	-10000	0	0
KLK2	-0.008	0.031	-9999	-0.24	2	2
CASP8	0.026	0	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	0.053	0.018	-9999	-10000	0	0
TMPRSS2	-0.004	0.025	-9999	-0.24	1	1
CCND1	0.025	0.01	-9999	-0.058	2	2
PIAS1	0.026	0.004	-9999	-10000	0	0
mol:T-DHT	0	0.001	-9999	-10000	0	0
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.025	0.006	-9999	-10000	0	0
T-DHT/AR/CDK6	0.027	0.022	-9999	-10000	0	0
CMTM2	0.026	0.003	-9999	-10000	0	0
SNURF	0.025	0.005	-9999	-10000	0	0
ZMIZ1	0.019	0.012	-9999	-10000	0	0
CCND3	0.026	0.004	-9999	-10000	0	0
TGIF1	0.019	0.022	-9999	-0.058	10	10
FKBP4	0.025	0.006	-9999	-10000	0	0

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.025	0.005	-10000	0	-10000	0	0
SMAD2	-0.019	0.047	-10000	0	-0.19	6	6
SMAD3	0.011	0.047	0.1	20	-10000	0	20
SMAD3/SMAD4	0.02	0.066	-10000	0	-0.41	3	3
SMAD4/Ubc9/PIASy	0.048	0.016	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.021	0.07	-10000	0	-0.19	6	6
PPM1A	0.025	0.006	-10000	0	-10000	0	0
CALM1	0.024	0.007	-10000	0	-10000	0	0
SMAD2/SMAD4	-0.006	0.054	-10000	0	-0.19	6	6
MAP3K1	0.026	0.004	-10000	0	-10000	0	0
TRAP-1/SMAD4	0.037	0.008	-10000	0	0	7	7
MAPK3	0.026	0.003	-10000	0	-10000	0	0
MAPK1	0.025	0.006	-10000	0	-10000	0	0
NUP214	0.025	0.006	-10000	0	-10000	0	0
CTDSP1	0.026	0	-10000	0	-10000	0	0
CTDSP2	0.022	0.01	-10000	0	-10000	0	0
CTDSPL	0.026	0.002	-10000	0	-10000	0	0
KPNB1	0.026	0	-10000	0	-10000	0	0
TGFBRAP1	0.026	0.002	-10000	0	-10000	0	0
UBE2I	0.026	0.004	-10000	0	-10000	0	0
NUP153	0.025	0.004	-10000	0	-10000	0	0
KPNA2	0.026	0.002	-10000	0	-10000	0	0
PIAS4	0.025	0.006	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	0.057	0.029	-9999	-0.028	12	12
HDAC3	0.026	0.003	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.024	0.003	-9999	-10000	0	0
GATA1/HDAC4	0.037	0.002	-9999	-10000	0	0
GATA1/HDAC5	0.037	0.004	-9999	0	1	1
GATA2/HDAC5	0.038	0.005	-9999	0	3	3
HDAC5/BCL6/BCoR	0.05	0.012	-9999	-10000	0	0
HDAC9	0.018	0.012	-9999	-10000	0	0
Glucocorticoid receptor/Hsp90/HDAC6	0.049	0.015	-9999	-10000	0	0
HDAC4/ANKRA2	0.038	0.005	-9999	0	3	3
HDAC5/YWHAB	0.035	0.011	-9999	0	14	14
NPC/RanGAP1/SUMO1/Ubc9	-0.002	0.029	-9999	-0.093	14	14
GATA2	0.026	0.003	-9999	-10000	0	0
HDAC4/RFXANK	0.037	0.008	-9999	0	7	7
BCOR	0.026	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.023	0.008	-9999	-10000	0	0
HDAC5	0.026	0.002	-9999	-10000	0	0
GNB1/GNG2	0.034	0.012	-9999	0	17	17
Histones	0.026	0.042	-9999	-10000	0	0
ADRBK1	0.026	0.002	-9999	-10000	0	0
HDAC4	0.026	0	-9999	-10000	0	0
XPO1	0.026	0	-9999	-10000	0	0
HDAC5/ANKRA2	0.038	0.006	-9999	0	4	4
HDAC4/Ubc9	0.038	0.005	-9999	0	3	3
HDAC7	0.025	0.006	-9999	-10000	0	0
HDAC5/14-3-3 E	0.038	0.006	-9999	0	4	4
TUBA1B	0.025	0.005	-9999	-10000	0	0
HDAC6	0.026	0	-9999	-10000	0	0
HDAC5/RFXANK	0.037	0.009	-9999	0	8	8
CAMK4	0.021	0.01	-9999	-10000	0	0
Tubulin/HDAC6	0.05	0.012	-9999	-10000	0	0
SUMO1	0.026	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.024	0.007	-9999	-10000	0	0
GATA1	0.024	0.003	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.026	0.004	-9999	-10000	0	0
NR3C1	0.026	0.003	-9999	-10000	0	0
SUMO1/HDAC4	0.026	0.04	-9999	-0.095	14	14
SRF	0.026	0.004	-9999	-10000	0	0
HDAC4/YWHAB	0.035	0.011	-9999	0	13	13
Tubulin	0.037	0.009	-9999	0	8	8
HDAC4/14-3-3 E	0.038	0.005	-9999	0	3	3
GNB1	0.025	0.006	-9999	-10000	0	0
RANGAP1	0.024	0.007	-9999	-10000	0	0
BCL6/BCoR	0.037	0.008	-9999	0	7	7
HDAC4/HDAC3/SMRT (N-CoR2)	0.051	0.011	-9999	-10000	0	0
HDAC4/SRF	0.043	0.021	-9999	-10000	0	0
HDAC4/ER alpha	0.035	0.012	-9999	0	15	15
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.026	0.042	-9999	-10000	0	0
cell motility	0.05	0.012	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.026	0.004	-9999	-10000	0	0
HDAC7/HDAC3	0.036	0.009	-9999	0	9	9
BCL6	0.025	0.006	-9999	-10000	0	0
HDAC4/CaMK II delta B	0.026	0	-9999	-10000	0	0
Hsp90/HDAC6	0.036	0.01	-9999	0	10	10
ESR1	0.023	0.008	-9999	-10000	0	0
HDAC6/HDAC11	0.039	0.003	-9999	0	1	1
Ran/GTP/Exportin 1	0.026	0.038	-9999	-0.094	13	13
NPC	0.015	0	-9999	-10000	0	0
MEF2C	0.025	0.005	-9999	-10000	0	0
RAN	0.026	0.004	-9999	-10000	0	0
HDAC4/MEF2C	0.07	0.025	-9999	-10000	0	0
GNG2	0.025	0.006	-9999	-10000	0	0
NCOR2	0.025	0.004	-9999	-10000	0	0
TUBB2A	0.025	0.004	-9999	-10000	0	0
HDAC11	0.026	0.002	-9999	-10000	0	0
HSP90AA1	0.024	0.007	-9999	-10000	0	0
RANBP2	0.026	0	-9999	-10000	0	0
ANKRA2	0.026	0.004	-9999	-10000	0	0
RFXANK	0.025	0.006	-9999	-10000	0	0
nuclear import	-0.026	0.009	-9999	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.025	0.004	-9999	0	-10000	0	0
PLK4	0.025	0.008	-9999	0	-0.058	1	1
regulation of centriole replication	-0.021	0.004	0	5	-0.046	1	6

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.024	0.007	-10000	0	-10000	0	0
VLDLR	0.023	0.009	-10000	0	-10000	0	0
LRPAP1	0.026	0	-10000	0	-10000	0	0
NUDC	0.025	0.004	-10000	0	-10000	0	0
RELN/LRP8	0.013	0.023	-10000	0	-10000	0	0
CaM/Ca2+	0.018	0.005	-10000	0	0	11	11
KATNA1	0.023	0.008	-10000	0	-10000	0	0
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	0.003	0.045	0.17	9	-10000	0	9
IQGAP1/CaM	0.035	0.011	-10000	0	0	14	14
DAB1	0.019	0.012	-10000	0	-10000	0	0
IQGAP1	0.026	0.004	-10000	0	0	3	3
PLA2G7	0.025	0.005	-10000	0	-10000	0	0
CALM1	0.024	0.007	-10000	0	-10000	0	0
DYNLT1	0.015	0.026	-10000	0	-0.058	15	15
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	0.037	0.008	-10000	0	0	6	6
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0.026	0.004	-10000	0	-10000	0	0
CDK5R1	0.023	0.008	-10000	0	-10000	0	0
LIS1/Poliovirus Protein 3A	-0.015	0.005	-10000	0	-10000	0	0
CDK5R2	0.016	0.013	-10000	0	-10000	0	0
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	0.009	0.02	-10000	0	-10000	0	0
YWHAE	0.026	0.004	-10000	0	-10000	0	0
NDEL1/14-3-3 E	0.005	0.12	0.28	20	-10000	0	20
MAP1B	0.003	0.001	-10000	0	-10000	0	0
RAC1	0.004	0.005	-10000	0	-10000	0	0
p35/CDK5	-0.014	0.031	0.17	3	-10000	0	3
RELN	0.007	0.011	-10000	0	-10000	0	0
PAFAH/LIS1	-0.022	0.009	-10000	0	-10000	0	0
LIS1/CLIP170	-0.023	0.008	-10000	0	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.037	0.045	0.11	2	-10000	0	2
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.004	0.044	0.12	1	-0.25	4	5
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	-0.004	0.064	0.28	6	-10000	0	6
LIS1/IQGAP1	-0.023	0.008	-10000	0	-10000	0	0
RHOA	0.006	0.004	-10000	0	-10000	0	0
PAFAH1B1	-0.019	0.007	-10000	0	-10000	0	0
PAFAH1B3	0.025	0.006	-10000	0	-10000	0	0
PAFAH1B2	0.026	0.002	-10000	0	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0.018	0.021	-10000	0	-0.1	3	3
NDEL1/Katanin 60/Dynein heavy chain	-0.008	0.1	0.28	14	-10000	0	14
LRP8	0.025	0.005	-10000	0	-10000	0	0
NDEL1/Katanin 60	-0.004	0.1	0.28	15	-10000	0	15
P39/CDK5	-0.012	0.021	0.16	1	-10000	0	1
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	-0.023	0.009	-10000	0	-10000	0	0
CDK5	-0.012	0.029	0.16	3	-10000	0	3
PPP2R5D	0.026	0.004	-10000	0	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	-0.019	0.006	-10000	0	-10000	0	0
CSNK2A1	0.024	0.007	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1	0.008	0.02	-10000	0	-10000	0	0
RELN/VLDLR	0.014	0.029	-10000	0	-0.028	4	4
CDC42	0.005	0.004	-10000	0	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.025	0.004	-10000	0	-10000	0	0
HDAC2	0.024	0.008	-10000	0	-10000	0	0
GNB1/GNG2	0.032	0.028	-10000	0	-0.043	1	1
forebrain development	0.057	0.056	0.23	7	-10000	0	7
GNAO1	0.024	0.007	-10000	0	-10000	0	0
SMO/beta Arrestin2	0.027	0.02	-10000	0	-10000	0	0
SMO	0.014	0.019	-10000	0	-0.058	6	6
ARRB2	0.026	0.004	-10000	0	-10000	0	0
GLI3/SPOP	0.012	0.061	-10000	0	-0.23	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
GSK3B	0.026	0.004	-10000	0	-10000	0	0
GNAI2	0.026	0.003	-10000	0	-10000	0	0
SIN3/HDAC complex	0.055	0.03	-10000	0	-0.028	13	13
GNAI1	0.017	0.012	-10000	0	-10000	0	0
XPO1	0.027	0	-10000	0	-10000	0	0
GLI1/Su(fu)	0.02	0.032	-10000	0	-10000	0	0
SAP30	0.025	0.005	-10000	0	-10000	0	0
mol:GDP	0.014	0.019	-10000	0	-0.058	6	6
MIM/GLI2A	0.025	0.006	-10000	0	-10000	0	0
IFT88	0.024	0.007	-10000	0	-10000	0	0
GNAI3	0.026	0.003	-10000	0	-10000	0	0
GLI2	0.004	0.052	0.16	5	-0.24	2	7
GLI3	0	0.056	-10000	0	-0.24	1	1
CSNK1D	0.026	0	-10000	0	-10000	0	0
CSNK1E	0.024	0.007	-10000	0	-10000	0	0
SAP18	0.024	0.007	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.024	0.007	-10000	0	-10000	0	0
GNG2	0.025	0.006	-10000	0	-10000	0	0
Gi family/GTP	0.009	0.021	-10000	0	-10000	0	0
SIN3B	0.025	0.005	-10000	0	-10000	0	0
SIN3A	0.026	0.004	-10000	0	-10000	0	0
GLI3/Su(fu)	0	0.064	-10000	0	-0.28	6	6
GLI2/Su(fu)	-0.001	0.054	-10000	0	-0.21	8	8
FOXA2	0.031	0.016	-10000	0	-10000	0	0
neural tube patterning	0.057	0.056	0.23	7	-10000	0	7
SPOP	0.026	0.002	-10000	0	-10000	0	0
Su(fu)/PIAS1	0.012	0.071	-10000	0	-0.17	17	17
GNB1	0.025	0.006	-10000	0	-10000	0	0
CSNK1G2	0.025	0.006	-10000	0	-10000	0	0
CSNK1G3	0.026	0.003	-10000	0	-10000	0	0
MTSS1	0.025	0.006	-10000	0	-10000	0	0
embryonic limb morphogenesis	0.057	0.056	0.23	7	-10000	0	7
SUFU	0.008	0.009	-10000	0	-0.056	1	1
LGALS3	0.012	0.03	-10000	0	-0.058	22	22
catabolic process	0.025	0.072	0.24	1	-0.3	3	4
GLI3A/CBP	0.029	0.006	-10000	0	-10000	0	0
KIF3A	0.026	0.003	-10000	0	-10000	0	0
GLI1	0.057	0.056	0.24	4	-10000	0	4
RAB23	0.026	0.003	-10000	0	-10000	0	0
CSNK1A1	0.026	0.003	-10000	0	-10000	0	0
IFT172	0.026	0.002	-10000	0	-10000	0	0
RBBP7	0.026	0	-10000	0	-10000	0	0
Su(fu)/Galectin3	0.014	0.073	0.12	1	-0.17	17	18
GNAZ	0.025	0.006	-10000	0	-10000	0	0
RBBP4	0.025	0.004	-10000	0	-10000	0	0
CSNK1G1	0.026	0.004	-10000	0	-10000	0	0
PIAS1	0.026	0.004	-10000	0	-10000	0	0
PRKACA	0.025	0.006	-10000	0	-10000	0	0
GLI2/SPOP	0.018	0.053	0.16	5	-0.23	2	7
STK36	0.026	0.002	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	0	0.03	0.095	1	-10000	0	1
PTCH1	0.05	0.055	-10000	0	-10000	0	0
MIM/GLI1	0.065	0.053	0.23	2	-10000	0	2
CREBBP	0.029	0.006	-10000	0	-10000	0	0
Su(fu)/SIN3/HDAC complex	-0.001	0.068	0.15	2	-0.23	8	10

×

Presenilin action in Notch and Wnt signaling

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
Delta 1/NOTCH/NOTCH(cleaved)	0.025	0.082	-10000	0	-0.36	6	6
HDAC1	0.025	0.004	-10000	0	-10000	0	0
AES	0.025	0.006	-10000	0	-10000	0	0
FBXW11	0.026	0.003	-10000	0	-10000	0	0
DTX1	0.025	0.005	-10000	0	-10000	0	0
LRP6/FZD1	0.025	0.019	-10000	0	0	53	53
TLE1	0.025	0.005	-10000	0	-10000	0	0
AP1	0.01	0.022	-10000	0	-0.21	1	1
NCSTN	0.026	0.003	-10000	0	-10000	0	0
ADAM10	0.025	0.004	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.029	0.05	-10000	0	-0.5	1	1
NICD/RBPSUH	0.024	0.082	-10000	0	-0.36	6	6
WIF1	0.008	0.011	-10000	0	-10000	0	0
NOTCH1	0.009	0.073	-10000	0	-0.43	4	4
PSENEN	0.025	0.006	-10000	0	-10000	0	0
KREMEN2	0.025	0.008	-10000	0	-0.058	1	1
DKK1	0.004	0.031	-10000	0	-0.058	26	26
beta catenin/beta TrCP1	0.062	0.078	0.21	13	-10000	0	13
APH1B	0.026	0.004	-10000	0	-10000	0	0
APH1A	0.026	0.003	-10000	0	-10000	0	0
AXIN1	0.02	0.046	0.24	1	-0.33	1	2
CtBP/CBP/TCF1/TLE1/AES	0.01	0.024	-10000	0	-10000	0	0
PSEN1	0.024	0.007	-10000	0	-10000	0	0
FOS	0.024	0.008	-10000	0	-10000	0	0
JUN	0.025	0.004	-10000	0	-10000	0	0
MAP3K7	0.023	0.008	-10000	0	-10000	0	0
CTNNB1	0.05	0.082	0.21	15	-10000	0	15
MAPK3	0.026	0.003	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.049	0.015	-10000	0	-10000	0	0
HNF1A	0.026	0.003	-10000	0	-10000	0	0
CTBP1	0.026	0	-10000	0	-10000	0	0
MYC	0.021	0.02	-10000	0	-10000	0	0
NKD1	0.025	0.004	-10000	0	-10000	0	0
FZD1	0.016	0.015	-10000	0	-0.058	2	2
NOTCH1 precursor/Deltex homolog 1	0.022	0.082	-10000	0	-0.36	6	6
apoptosis	0.01	0.022	-10000	0	-0.21	1	1
Delta 1/NOTCHprecursor	0.021	0.082	-10000	0	-0.36	6	6
DLL1	0.024	0.008	-10000	0	-10000	0	0
PPARD	0.014	0.093	-10000	0	-0.77	2	2
Gamma Secretase	0.063	0.035	-10000	0	-10000	0	0
APC	0.016	0.053	-10000	0	-0.34	2	2
DVL1	0.003	0.033	-10000	0	-0.2	3	3
CSNK2A1	0.024	0.007	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	0.039	0.029	-10000	0	-0.061	1	1
LRP6	0.025	0.006	-10000	0	-10000	0	0
CSNK1A1	0.026	0.003	-10000	0	-10000	0	0
NLK	0.007	0.003	-10000	0	-10000	0	0
CCND1	0.019	0.064	-10000	0	-0.74	1	1
WNT1	0.024	0.006	-10000	0	-10000	0	0
Axin1/APC/beta catenin	0.039	0.072	0.26	4	-0.28	1	5
DKK2	0.025	0.008	-10000	0	-0.058	1	1
NOTCH1 precursor/DVL1	0.021	0.072	-10000	0	-0.32	3	3
GSK3B	0.026	0.004	-10000	0	-10000	0	0
FRAT1	0.019	0.012	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	0.027	0.082	-10000	0	-0.36	6	6
PPP2R5D	0.013	0.054	-10000	0	-0.28	4	4
MAPK1	0.025	0.006	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.017	0.03	-10000	0	-0.029	2	2
RBPJ	0.026	0.002	-10000	0	-10000	0	0
CREBBP	0.026	0.004	-10000	0	-10000	0	0

×

IL4-mediated signaling events

Figure S110. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S110. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.062	0.16	-10000	0	-10000	0	0
STAT6 (cleaved dimer)	-0.071	0.16	-10000	0	-10000	0	0
IGHG1	-0.026	0.081	-10000	0	-10000	0	0
IGHG3	-0.072	0.15	-10000	0	-10000	0	0
AKT1	-0.036	0.11	-10000	0	-0.55	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.02	0.087	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.032	0.1	-10000	0	-10000	0	0
THY1	-0.083	0.17	-10000	0	-0.92	1	1
MYB	0.013	0.028	-10000	0	-0.058	18	18
HMGA1	0.026	0.003	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.051	0.12	-10000	0	-0.55	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.032	0.1	-10000	0	-10000	0	0
SP1	0.026	0.004	-10000	0	-10000	0	0
INPP5D	0.026	0	-10000	0	-10000	0	0
SOCS5	0.027	0.018	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.066	0.17	-10000	0	-10000	0	0
SOCS1	-0.068	0.15	-10000	0	-10000	0	0
SOCS3	-0.051	0.11	-10000	0	-0.48	1	1
FCER2	-0.28	0.43	-10000	0	-0.86	51	51
PARP14	-0.002	0.038	-10000	0	-0.055	50	50
CCL17	-0.08	0.16	-10000	0	-10000	0	0
GRB2	0.025	0.004	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.025	0.088	-10000	0	-10000	0	0
T cell proliferation	-0.073	0.15	-10000	0	-10000	0	0
IL4R/JAK1	-0.068	0.16	-10000	0	-10000	0	0
EGR2	-0.14	0.23	-10000	0	-0.74	1	1
JAK2	0.004	0.035	-10000	0	-10000	0	0
JAK3	0.012	0.023	-10000	0	-0.04	2	2
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
JAK1	0.01	0.026	-10000	0	-0.056	1	1
COL1A2	-0.018	0.088	-10000	0	-0.5	1	1
CCL26	-0.014	0.18	-10000	0	-10000	0	0
IL4R	-0.08	0.16	-10000	0	-10000	0	0
PTPN6	0.026	0.013	-10000	0	-0.031	1	1
IL13RA2	-0.088	0.18	-10000	0	-1	2	2
IL13RA1	0.01	0.038	-10000	0	-10000	0	0
IRF4	-0.024	0.089	-10000	0	-10000	0	0
ARG1	-0.034	0.1	-10000	0	-0.39	2	2
CBL	-0.054	0.12	-10000	0	-0.53	1	1
GTF3A	0.024	0.008	-10000	0	-10000	0	0
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
IL13RA1/JAK2	0.009	0.047	-10000	0	-10000	0	0
IRF4/BCL6	0.008	0.067	-10000	0	-10000	0	0
CD40LG	0.006	0.03	-10000	0	-0.074	2	2
MAPK14	-0.052	0.12	-10000	0	-0.53	1	1
mitosis	-0.033	0.11	-10000	0	-0.52	1	1
STAT6	-0.083	0.17	-10000	0	-10000	0	0
SPI1	0.026	0.008	-10000	0	-0.057	1	1
RPS6KB1	-0.037	0.11	-10000	0	-0.52	1	1
STAT6 (dimer)	-0.082	0.17	-10000	0	-10000	0	0
STAT6 (dimer)/PARP14	-0.11	0.22	-10000	0	-0.72	1	1
mast cell activation	0.004	0.007	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.033	0.1	-10000	0	-10000	0	0
FRAP1	-0.035	0.11	-10000	0	-0.55	1	1
LTA	-0.081	0.15	-10000	0	-10000	0	0
FES	0.026	0.004	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0.082	0.17	-10000	0	-10000	0	0
CCL11	-0.079	0.15	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.033	0.1	-10000	0	-10000	0	0
IL2RG	0.006	0.03	-10000	0	-0.059	11	11
IL10	-0.076	0.15	-10000	0	-10000	0	0
IRS1	0.026	0	-10000	0	-10000	0	0
IRS2	0.025	0.006	-10000	0	-10000	0	0
IL4	-0.02	0.094	-10000	0	-0.63	2	2
IL5	-0.081	0.15	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.077	0.16	-10000	0	-10000	0	0
COL1A1	-0.049	0.14	-10000	0	-0.68	3	3
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.07	0.16	-10000	0	-10000	0	0
IL2R gamma/JAK3	0.022	0.034	-10000	0	-0.05	6	6
TFF3	-0.079	0.16	-10000	0	-10000	0	0
ALOX15	-0.081	0.15	-10000	0	-10000	0	0
MYBL1	0.026	0.004	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.072	0.15	-10000	0	-10000	0	0
SHC1	0.023	0.013	-10000	0	-0.058	3	3
CEBPB	0.024	0.01	-10000	0	-0.057	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.033	0.1	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.035	0.11	-10000	0	-0.55	1	1
PI3K	-0.036	0.12	-10000	0	-0.57	1	1
DOK2	0.02	0.021	-10000	0	-0.058	10	10
ETS1	0.026	0.016	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.023	0.085	-10000	0	-10000	0	0
ITGB3	-0.081	0.15	-10000	0	-10000	0	0
PIGR	-0.075	0.15	-10000	0	-10000	0	0
IGHE	0.01	0.042	0.14	8	-0.089	1	9
MAPKKK cascade	-0.023	0.085	-10000	0	-10000	0	0
BCL6	0.033	0.013	-10000	0	-10000	0	0
OPRM1	-0.08	0.15	-10000	0	-10000	0	0
RETNLB	-0.081	0.16	-10000	0	-10000	0	0
SELP	-0.078	0.15	-10000	0	-10000	0	0
AICDA	-0.072	0.15	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class III

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
EP300	0.024	0.007	-10000	0	-10000	0	0
HDAC4	0.026	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.016	0.011	-10000	0	-10000	0	0
CDKN1A	-0.011	0.012	0.062	2	-10000	0	2
KAT2B	0.026	0.002	-10000	0	-10000	0	0
BAX	0.025	0.006	-10000	0	-10000	0	0
FOXO3	0.002	0.01	0.023	24	-10000	0	24
FOXO1	0.025	0.006	-10000	0	-10000	0	0
FOXO4	0.007	0.002	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.024	0.007	-10000	0	-10000	0	0
TAT	0.019	0.02	-10000	0	-0.058	9	9
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.022	0.005	-10000	0	-0.047	2	2
PPARGC1A	0.026	0.002	-10000	0	-10000	0	0
FHL2	0.026	0	-10000	0	-10000	0	0
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.026	0.018	-10000	0	-10000	0	0
HIST2H4A	-0.016	0.011	-10000	0	-10000	0	0
SIRT1/FOXO3a	0.016	0.019	0.14	2	-10000	0	2
SIRT1	0.015	0.015	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.036	0.024	-10000	0	-10000	0	0
SIRT1/Histone H1b	0.012	0.033	-10000	0	-0.14	5	5
apoptosis	-0.035	0.024	-10000	0	-10000	0	0
SIRT1/PGC1A	0.024	0.016	-10000	0	-10000	0	0
p53/SIRT1	0.027	0.018	-10000	0	-10000	0	0
SIRT1/FOXO4	0.015	0.023	-10000	0	-0.11	3	3
FOXO1/FHL2/SIRT1	0.028	0.032	-10000	0	-0.021	44	44
HIST1H1E	0.007	0.002	-10000	0	-10000	0	0
SIRT1/p300	0.026	0.018	-10000	0	-10000	0	0
muscle cell differentiation	-0.017	0.018	-10000	0	-10000	0	0
TP53	0.018	0.021	-10000	0	-0.06	6	6
KU70/SIRT1/BAX	0.036	0.025	-10000	0	-10000	0	0
CREBBP	0.026	0.004	-10000	0	-10000	0	0
MEF2D	0.025	0.004	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.027	0.018	-10000	0	-10000	0	0
ACSS2	-0.016	0.011	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	0.017	0.019	-10000	0	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	-0.003	0.065	0.31	6	-10000	0	6
VDR	0.023	0.015	-10000	0	-0.058	4	4
FAM120B	0.024	0.008	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.003	0.05	-10000	0	-0.2	3	3
RXRs/LXRs/DNA/Oxysterols	-0.002	0.06	-10000	0	-0.3	2	2
MED1	0.026	0	-10000	0	-10000	0	0
mol:9cRA	0.001	0.005	-10000	0	-0.039	2	2
RARs/THRs/DNA/Src-1	0.009	0.032	-10000	0	-10000	0	0
RXRs/NUR77	0.051	0.037	-10000	0	-0.095	2	2
RXRs/PPAR	-0.01	0.06	-10000	0	-0.21	6	6
NCOR2	0.025	0.004	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.019	0.005	0.041	4	0	7	11
RARs/VDR/DNA/Vit D3	0.059	0.018	-10000	0	-0.026	4	4
RARA	0.026	0	-10000	0	-10000	0	0
NCOA1	0.026	0.003	-10000	0	-10000	0	0
VDR/VDR/DNA	0.023	0.015	-10000	0	-0.058	4	4
RARs/RARs/DNA/9cRA	0.045	0.013	-10000	0	-0.036	2	2
RARG	0.025	0.008	-10000	0	-0.058	1	1
RPS6KB1	-0.006	0.066	0.55	2	-10000	0	2
RARs/THRs/DNA/SMRT	0.01	0.031	-10000	0	-10000	0	0
THRA	0.026	0	-10000	0	-10000	0	0
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.019	0.005	0.041	4	0	7	11
RXRs/PPAR/9cRA/PGJ2/DNA	0.041	0.03	-10000	0	-0.13	2	2
NR1H4	0.02	0.019	-10000	0	-0.058	8	8
RXRs/LXRs/DNA	0.056	0.051	-10000	0	-0.17	2	2
NR1H2	0.025	0.011	-10000	0	-0.053	2	2
NR1H3	0.026	0.011	-10000	0	-0.058	2	2
RXRs/VDR/DNA/Vit D3	0.046	0.036	-10000	0	-0.088	2	2
NR4A1	0.025	0.005	-10000	0	-10000	0	0
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.005	0.047	-10000	0	-0.2	3	3
RXRG	0.022	0.013	-10000	0	-0.054	2	2
RXR alpha/CCPG	0.034	0.016	-10000	0	-0.044	2	2
RXRA	0.025	0.011	-10000	0	-0.054	2	2
RXRB	0.026	0.01	-10000	0	-0.058	2	2
THRB	0.024	0.007	-10000	0	0	12	12
PPARG	0.026	0.002	-10000	0	-10000	0	0
PPARD	0.026	0.003	-10000	0	-10000	0	0
TNF	-0.012	0.082	-10000	0	-0.62	2	2
mol:Oxysterols	0.001	0.004	-10000	0	-0.034	2	2
cholesterol transport	-0.002	0.06	-10000	0	-0.3	2	2
PPARA	0.023	0.008	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.026	0.002	-10000	0	-10000	0	0
RXRs/NUR77/BCL2	-0.005	0.044	-10000	0	-0.2	1	1
SREBF1	-0.01	0.055	-10000	0	-0.29	2	2
RXRs/RXRs/DNA/9cRA	0.041	0.03	-10000	0	-0.13	2	2
ABCA1	-0.007	0.05	-10000	0	-0.29	2	2
RARs/THRs	0.069	0.028	-10000	0	-10000	0	0
RXRs/FXR	0.052	0.036	-10000	0	-0.095	2	2
BCL2	0.025	0.005	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	0.043	0.058	-10000	0	-0.16	4	4
Ran/GTP/Exportin 1/HDAC1	-0.023	0.004	0	5	-10000	0	5
NF kappa B1 p50/RelA/I kappa B alpha	0.012	0.064	-10000	0	-0.21	6	6
SUMO1	0.026	0	-10000	0	-10000	0	0
ZFPM1	0.025	0.006	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	-0.002	0.029	-10000	0	-0.093	14	14
FKBP3	0.024	0.007	-10000	0	-10000	0	0
Histones	0.049	0.037	-10000	0	-0.2	1	1
YY1/LSF	0.004	0.059	-10000	0	-0.24	3	3
SMG5	0.025	0.004	-10000	0	-10000	0	0
RAN	0.026	0.004	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	0.009	0.027	-10000	0	-0.084	11	11
I kappa B alpha/HDAC1	0.015	0.055	-10000	0	-0.17	11	11
SAP18	0.024	0.007	-10000	0	-10000	0	0
RELA	0	0.049	0.12	4	-0.14	12	16
HDAC1/Smad7	0.035	0.025	-10000	0	-10000	0	0
RANGAP1	0.024	0.007	-10000	0	-10000	0	0
HDAC3/TR2	0.025	0.034	-10000	0	-0.21	2	2
NuRD/MBD3 Complex	0.005	0.039	-10000	0	-0.19	2	2
NF kappa B1 p50/RelA	0.012	0.063	-10000	0	-0.32	2	2
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	0.026	0.003	-10000	0	-10000	0	0
GATA1	0.024	0.003	-10000	0	-10000	0	0
Mad/Max	0.036	0.01	-10000	0	0	10	10
NuRD/MBD3 Complex/GATA1/Fog1	0.004	0.041	-10000	0	-0.16	4	4
RBBP7	0.026	0	-10000	0	-10000	0	0
NPC	0.015	0	-10000	0	-10000	0	0
RBBP4	0.025	0.004	-10000	0	-10000	0	0
MAX	0.024	0.007	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.026	0.003	-10000	0	-10000	0	0
NFKBIA	0.012	0.009	-10000	0	-0.056	2	2
KAT2B	0.026	0.002	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	-0.005	0.049	-10000	0	-0.2	5	5
SIN3 complex	0.055	0.03	-10000	0	-0.028	13	13
SMURF1	0.018	0.012	-10000	0	-10000	0	0
CHD3	0.025	0.005	-10000	0	-10000	0	0
SAP30	0.025	0.005	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.026	0.002	-10000	0	-10000	0	0
YY1/HDAC3	0.001	0.05	-10000	0	-0.18	5	5
YY1/HDAC2	0.006	0.057	-10000	0	-0.24	3	3
YY1/HDAC1	0.006	0.058	-10000	0	-0.24	3	3
NuRD/MBD2 Complex (MeCP1)	0.007	0.046	-10000	0	-0.24	2	2
PPARG	0.01	0.032	0.13	4	-0.1	7	11
HDAC8/hEST1B	0.049	0.014	-10000	0	-10000	0	0
UBE2I	0.026	0.004	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.026	0.003	-10000	0	-10000	0	0
TNFRSF1A	0.025	0.005	-10000	0	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.025	0.034	-10000	0	-0.21	2	2
MBD3L2	0.019	0.004	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.034	0.025	-10000	0	-10000	0	0
CREBBP	0.026	0.004	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.015	0.025	-10000	0	-0.17	1	1
HDAC1	0.025	0.004	-10000	0	-10000	0	0
HDAC3	0.012	0.012	-10000	0	-0.056	4	4
HDAC2	0.024	0.008	-10000	0	-10000	0	0
YY1	0.008	0.004	-10000	0	-10000	0	0
HDAC8	0.026	0	-10000	0	-10000	0	0
SMAD7	0.025	0.005	-10000	0	-10000	0	0
NCOR2	0.025	0.004	-10000	0	-10000	0	0
MXD1	0.026	0	-10000	0	-10000	0	0
STAT3	0.012	0.004	-10000	0	-10000	0	0
NFKB1	0.026	0.002	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.026	0	-10000	0	-10000	0	0
YY1/LSF/HDAC1	0.017	0.061	-10000	0	-0.23	3	3
YY1/SAP30/HDAC1	0.017	0.061	-10000	0	-0.23	3	3
EP300	0.024	0.007	-10000	0	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.012	0.004	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.012	0.009	-10000	0	-0.056	2	2
histone deacetylation	0.007	0.046	-10000	0	-0.24	2	2
STAT3 (dimer non-phopshorylated)/HDAC3	0.008	0.037	-10000	0	-0.14	2	2
nuclear export	-0.049	0.014	-10000	0	-10000	0	0
PRKACA	0.025	0.006	-10000	0	-10000	0	0
GATAD2B	0.026	0.004	-10000	0	-10000	0	0
GATAD2A	0.025	0.006	-10000	0	-10000	0	0
GATA2/HDAC3	0.027	0.035	-10000	0	-0.21	2	2
GATA1/HDAC1	0.036	0.006	-10000	0	0	4	4
GATA1/HDAC3	0.025	0.035	-10000	0	-0.21	2	2
CHD4	0.025	0.005	-10000	0	-10000	0	0
TNF-alpha/TNFR1A	0.036	0.01	-10000	0	0	11	11
SIN3/HDAC complex/Mad/Max	-0.005	0.061	-10000	0	-0.21	8	8
NuRD Complex	0.015	0.029	-10000	0	-0.16	1	1
positive regulation of chromatin silencing	0.046	0.036	-10000	0	-0.2	1	1
SIN3B	0.025	0.005	-10000	0	-10000	0	0
MTA2	0.026	0.002	-10000	0	-10000	0	0
SIN3A	0.026	0.004	-10000	0	-10000	0	0
XPO1	0.026	0	-10000	0	-10000	0	0
SUMO1/HDAC1	0.025	0.04	-10000	0	-0.095	14	14
HDAC complex	0.057	0.029	-10000	0	-10000	0	0
GATA1/Fog1	0.035	0.008	-10000	0	0	7	7
FKBP25/HDAC1/HDAC2	0.044	0.02	-10000	0	-10000	0	0
TNF	0.025	0.005	-10000	0	-10000	0	0
negative regulation of cell growth	-0.005	0.061	-10000	0	-0.21	8	8
NuRD/MBD2/PRMT5 Complex	0.007	0.046	-10000	0	-0.24	2	2
Ran/GTP/Exportin 1	0.026	0.038	-10000	0	-0.094	13	13
NF kappa B/RelA/I kappa B alpha	-0.001	0.054	-10000	0	-0.18	9	9
SIN3/HDAC complex/NCoR1	0.011	0.024	-10000	0	-0.18	1	1
TFCP2	0.025	0.005	-10000	0	-10000	0	0
NR2C1	0.026	0.004	-10000	0	-10000	0	0
MBD3	0.025	0.006	-10000	0	-10000	0	0
MBD2	0.025	0.005	-10000	0	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.025	0.006	-10000	0	-10000	0	0
Rac1/GDP	0.019	0.016	-10000	0	-0.025	2	2
DOCK1	0.017	0.012	-10000	0	-10000	0	0
ITGA4	0.013	0.031	-10000	0	-0.058	23	23
RAC1	0.017	0.012	-10000	0	-10000	0	0
alpha4/beta7 Integrin	0.041	0.01	-10000	0	0	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.026	0.004	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.04	0.028	0.092	2	-0.043	1	3
alpha4/beta7 Integrin/Paxillin	0.04	0.016	0.17	1	-10000	0	1
lamellipodium assembly	-0.006	0.067	-10000	0	-0.3	5	5
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
PI3K	0.036	0.01	-10000	0	0	10	10
ARF6	0.025	0.006	-10000	0	-10000	0	0
TLN1	0.023	0.008	-10000	0	-10000	0	0
PXN	-0.021	0.005	-10000	0	-10000	0	0
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
ARF6/GTP	0.027	0.042	-10000	0	-10000	0	0
cell adhesion	0.03	0.039	-10000	0	-10000	0	0
CRKL/CBL	0.037	0.009	-10000	0	0	8	8
alpha4/beta1 Integrin/Paxillin	0.03	0.021	-10000	0	-10000	0	0
ITGB1	0.017	0.015	-10000	0	-0.058	2	2
ITGB7	0.026	0.004	-10000	0	-10000	0	0
ARF6/GDP	0.027	0.012	-10000	0	-0.025	2	2
alpha4/beta1 Integrin/Paxillin/VCAM1	0.035	0.045	0.14	2	-0.065	1	3
p130Cas/Crk/Dock1	0.035	0.025	-10000	0	-10000	0	0
VCAM1	0.007	0.035	-10000	0	-0.058	33	33
alpha4/beta1 Integrin/Paxillin/Talin	0.031	0.04	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.031	0.04	-10000	0	-10000	0	0
BCAR1	0.025	0.005	-10000	0	-10000	0	0
mol:GDP	-0.03	0.039	-10000	0	-10000	0	0
CBL	0.026	0.002	-10000	0	-10000	0	0
PRKACA	0.025	0.006	-10000	0	-10000	0	0
GIT1	0.026	0.004	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.031	0.04	-10000	0	-10000	0	0
Rac1/GTP	-0.007	0.073	-10000	0	-0.34	5	5

×

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

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
BAG4	0.026	0.004	-10000	0	-10000	0	0
Caspase 8 (4 units)	-0.008	0.074	-10000	0	-0.16	12	12
NEF	0	0.004	-10000	0	-0.046	1	1
NFKBIA	0.024	0.009	-10000	0	-0.027	2	2
BIRC3	-0.028	0.017	0.17	1	-10000	0	1
CYCS	-0.016	0.035	0.16	2	-10000	0	2
RIPK1	0.025	0.005	-10000	0	-10000	0	0
CD247	0.025	0.01	-10000	0	-0.031	4	4
MAP2K7	-0.019	0.095	-10000	0	-0.4	2	2
protein ubiquitination	0.003	0.049	0.19	1	-0.24	3	4
CRADD	0.025	0.004	-10000	0	-10000	0	0
DAXX	0.026	0.003	-10000	0	-10000	0	0
FAS	0.015	0.019	-10000	0	-0.058	6	6
BID	-0.025	0.04	0.15	1	-0.11	1	2
NF-kappa-B/RelA/I kappa B alpha	0.051	0.016	-10000	0	-0.048	1	1
TRADD	0.026	0.003	-10000	0	-10000	0	0
MAP3K5	0.023	0.008	-10000	0	-10000	0	0
CFLAR	0.026	0	-10000	0	-10000	0	0
FADD	0.026	0.002	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.051	0.016	-10000	0	-0.048	1	1
MAPK8	-0.014	0.087	-10000	0	-0.38	2	2
APAF1	0.026	0.004	-10000	0	-10000	0	0
TRAF1	0.025	0.005	-10000	0	-10000	0	0
TRAF2	0.025	0.005	-10000	0	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.008	0.014	0.17	1	-10000	0	1
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.018	0.048	-10000	0	-0.26	2	2
CHUK	0.006	0.045	0.2	1	-0.26	2	3
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.042	0.052	-10000	0	-10000	0	0
TCRz/NEF	0.02	0.009	-10000	0	-0.03	4	4
TNF	0.025	0.005	-10000	0	-10000	0	0
FASLG	-0.016	0.006	-10000	0	-0.047	4	4
NFKB1	0.025	0.008	-10000	0	-0.028	3	3
TNFR1A/BAG4/TNF-alpha	0.048	0.016	-10000	0	-10000	0	0
CASP6	0	0.077	-10000	0	-10000	0	0
CASP7	-0.062	0.11	0.16	2	-0.26	25	27
RELA	0.025	0.008	-10000	0	-0.028	3	3
CASP2	0.018	0.012	-10000	0	-10000	0	0
CASP3	-0.026	0.061	0.16	1	-0.26	4	5
TNFRSF1A	0.025	0.005	-10000	0	-10000	0	0
TNFR1A/BAG4	0.036	0.009	-10000	0	0	9	9
CASP8	0.026	0	-10000	0	-10000	0	0
CASP9	0.025	0.005	-10000	0	-10000	0	0
MAP3K14	0.013	0.047	-10000	0	-0.25	2	2
APAF-1/Caspase 9	-0.014	0.064	0.12	19	-0.15	1	20
BCL2	-0.024	0.09	0.24	1	-0.36	2	3

×

Neurotrophic factor-mediated Trk receptor 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
CRKL	0.025	0.006	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	0.008	0.025	-10000	0	-0.14	1	1
NT3 (dimer)/TRKC	0.034	0.01	-10000	0	0	11	11
NT3 (dimer)/TRKB	0.049	0.019	0.092	1	-0.043	1	2
SHC/Grb2/SOS1/GAB1/PI3K	0.014	0.022	-10000	0	-10000	0	0
RAPGEF1	0.025	0.006	-10000	0	-10000	0	0
BDNF	0.017	0.013	-10000	0	-10000	0	0
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
DYNLT1	0.015	0.026	-10000	0	-0.058	15	15
NTRK1	0.02	0.021	-10000	0	-0.058	9	9
NTRK2	0.025	0.005	-10000	0	-10000	0	0
NTRK3	0.025	0.004	-10000	0	-10000	0	0
NT-4/5 (dimer)/TRKB	0.049	0.018	0.092	2	-10000	0	2
neuron apoptosis	0.01	0.07	0.22	4	-10000	0	4
SHC 2-3/Grb2	-0.011	0.074	-10000	0	-0.23	4	4
SHC1	0.023	0.013	-10000	0	-0.058	3	3
SHC2	-0.014	0.056	-10000	0	-10000	0	0
SHC3	-0.025	0.082	-10000	0	-0.35	5	5
STAT3 (dimer)	0.029	0.001	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	0.05	0.018	0.092	1	-0.043	1	2
RIN/GDP	0.013	0.053	0.18	5	-0.2	2	7
GIPC1	0.025	0.006	-10000	0	-10000	0	0
KRAS	0.025	0.006	-10000	0	-10000	0	0
DNAJA3	-0.008	0.022	0.083	7	-10000	0	7
RIN/GTP	0.016	0.007	-10000	0	-10000	0	0
CCND1	-0.02	0.003	-10000	0	-0.042	2	2
MAGED1	0.026	0	-10000	0	-10000	0	0
PTPN11	0.025	0.004	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.02	0.014	-10000	0	-0.058	4	4
SHC/GRB2/SOS1	0.05	0.013	-10000	0	-10000	0	0
GRB2	0.025	0.004	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	0.028	0.027	-10000	0	-10000	0	0
TRKA/NEDD4-2	0.037	0.011	-10000	0	0	10	10
ELMO1	0.017	0.012	-10000	0	-10000	0	0
RhoG/GTP/ELMO1/DOCK1	0.019	0.018	-10000	0	0	69	69
NGF	0.025	0.004	-10000	0	-10000	0	0
HRAS	0.025	0.006	-10000	0	-10000	0	0
DOCK1	0.017	0.012	-10000	0	-10000	0	0
GAB2	0.026	0.002	-10000	0	-10000	0	0
RIT2	0.021	0.01	-10000	0	-10000	0	0
RIT1	0.026	0.004	-10000	0	-10000	0	0
FRS2	0.024	0.007	-10000	0	-10000	0	0
DNM1	0.016	0.013	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.026	0.004	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	0.019	0.021	-10000	0	-10000	0	0
mol:GDP	0.011	0.08	0.26	6	-0.29	2	8
NGF (dimer)	0.025	0.004	-10000	0	-10000	0	0
RhoG/GDP	0.013	0.009	-10000	0	-10000	0	0
RIT1/GDP	0.017	0.063	0.22	6	-0.2	2	8
TIAM1	0.026	0.004	-10000	0	-10000	0	0
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	0.032	0.026	-10000	0	-10000	0	0
KIDINS220/CRKL/C3G	0.035	0.011	-10000	0	0	14	14
SHC/RasGAP	0.037	0.009	-10000	0	0	7	7
FRS2 family/SHP2	0.048	0.015	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0.063	0.019	-10000	0	-10000	0	0
RIT1/GTP	0.019	0.003	-10000	0	-10000	0	0
NT3 (dimer)	0.021	0.011	-10000	0	-0.058	2	2
RAP1/GDP	0.01	0.042	0.15	1	-0.17	2	3
KIDINS220/CRKL	0.025	0.006	-10000	0	-10000	0	0
BDNF (dimer)	0.017	0.013	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.05	0.015	-10000	0	-10000	0	0
Schwann cell development	-0.007	0.008	-10000	0	-10000	0	0
EHD4	0.025	0.008	-10000	0	-0.058	1	1
FRS2 family/GRB2/SOS1	0.059	0.023	-10000	0	-0.027	3	3
FRS2 family/SHP2/CRK family/C3G/GAB2	0.012	0.035	-10000	0	-0.19	2	2
RAP1B	0.023	0.01	-10000	0	-0.058	1	1
RAP1A	0.026	0.004	-10000	0	-10000	0	0
CDC42/GTP	0.016	0.042	0.14	4	-10000	0	4
ABL1	0.025	0.006	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.038	0.006	-10000	0	0	4	4
Rap1/GTP	-0.001	0.057	-10000	0	-0.21	9	9
STAT3	0.029	0.001	-10000	0	-10000	0	0
axon guidance	-0.035	0.011	-10000	0	-10000	0	0
MAPK3	-0.01	0.041	0.17	6	-10000	0	6
MAPK1	-0.01	0.04	0.17	6	-10000	0	6
CDC42/GDP	0.014	0.053	0.16	5	-0.2	2	7
NTF3	0.021	0.011	-10000	0	-0.058	2	2
NTF4	0.02	0.014	-10000	0	-0.058	4	4
NGF (dimer)/TRKA/FAIM	0.051	0.013	-10000	0	-10000	0	0
PI3K	0.036	0.01	-10000	0	0	10	10
FRS3	0.026	0.003	-10000	0	-10000	0	0
FAIM	0.026	0.004	-10000	0	-10000	0	0
GAB1	0.026	0.004	-10000	0	-10000	0	0
RASGRF1	-0.002	0.012	0.083	2	-10000	0	2
SOS1	0.026	0	-10000	0	-10000	0	0
MCF2L	-0.023	0.009	-10000	0	-0.045	1	1
RGS19	0.023	0.008	-10000	0	-10000	0	0
CDC42	0.026	0.004	-10000	0	-10000	0	0
RAS family/GTP	0.018	0.043	-10000	0	-10000	0	0
Rac1/GDP	0.013	0.048	0.25	3	-10000	0	3
NGF (dimer)/TRKA/GRIT	0.035	0.009	-10000	0	0	6	6
neuron projection morphogenesis	0.026	0.033	-10000	0	-10000	0	0
NGF (dimer)/TRKA/NEDD4-2	0.05	0.015	-10000	0	-10000	0	0
MAP2K1	-0.023	0.046	0.17	8	-10000	0	8
NGFR	0.013	0.03	-10000	0	-0.058	22	22
NGF (dimer)/TRKA/GIPC/GAIP	-0.025	0.056	-10000	0	-0.19	3	3
RAS family/GTP/PI3K	0.006	0.031	-10000	0	-0.1	9	9
FRS2 family/SHP2/GRB2/SOS1	0.068	0.027	-10000	0	-10000	0	0
NRAS	0.026	0.003	-10000	0	-10000	0	0
GRB2/SOS1	0.038	0.006	-10000	0	0	4	4
PRKCI	0.026	0.003	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.017	0.012	-10000	0	-10000	0	0
PRKCZ	0.019	0.011	-10000	0	-10000	0	0
MAPKKK cascade	0.031	0.053	-10000	0	-0.43	1	1
RASA1	0.026	0.004	-10000	0	-10000	0	0
TRKA/c-Abl	0.037	0.012	-10000	0	0	12	12
SQSTM1	0.026	0.003	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	0.034	0.039	-10000	0	-0.029	7	7
NGF (dimer)/TRKA/p62/Atypical PKCs	0.05	0.044	-10000	0	-10000	0	0
MATK	0.014	0.013	-10000	0	-10000	0	0
NEDD4L	0.025	0.005	-10000	0	-10000	0	0
RAS family/GDP	-0.011	0.029	-10000	0	-0.14	3	3
NGF (dimer)/TRKA	0.012	0.014	-10000	0	-10000	0	0
Rac1/GTP	-0.012	0.019	-10000	0	-0.12	1	1
FRS2 family/SHP2/CRK family	0.065	0.033	-10000	0	-10000	0	0

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.026	0.003	-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	0.062	0.18	2	-0.23	3	5
ERC1	0.025	0.006	-10000	0	-10000	0	0
RIP2/NOD2	0.041	0.013	-10000	0	0	7	7
NFKBIA	-0.025	0.02	0.2	1	-10000	0	1
BIRC2	0.026	0.002	-10000	0	-10000	0	0
IKBKB	0.026	0.004	-10000	0	-10000	0	0
RIPK2	0.025	0.004	-10000	0	-10000	0	0
IKBKG	0.012	0.046	-10000	0	-0.35	2	2
IKK complex/A20	0.048	0.053	-10000	0	-0.33	2	2
NEMO/A20/RIP2	0.025	0.004	-10000	0	-10000	0	0
XPO1	0.026	0	-10000	0	-10000	0	0
NEMO/ATM	0.029	0.049	-10000	0	-0.34	2	2
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.026	0.004	-10000	0	-10000	0	0
Exportin 1/RanGTP	0.035	0.005	-10000	0	0	3	3
IKK complex/ELKS	0.028	0.051	-10000	0	-0.32	2	2
BCL10/MALT1/TRAF6	0.049	0.014	-10000	0	-10000	0	0
NOD2	0.008	0.034	-10000	0	-0.058	31	31
NFKB1	0.026	0.002	-10000	0	-10000	0	0
RELA	0.026	0.003	-10000	0	-10000	0	0
MALT1	0.025	0.005	-10000	0	-10000	0	0
cIAP1/UbcH5C	0.038	0.004	-10000	0	0	2	2
ATM	0.026	0.002	-10000	0	-10000	0	0
TNF/TNFR1A	0.036	0.01	-10000	0	0	11	11
TRAF6	0.026	0.003	-10000	0	-10000	0	0
PRKCA	0.026	0.002	-10000	0	-10000	0	0
CHUK	0.018	0.012	-10000	0	-10000	0	0
UBE2D3	0.026	0.002	-10000	0	-10000	0	0
TNF	0.025	0.005	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.054	0.009	-10000	0	-10000	0	0
BCL10	0.025	0.005	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.025	0.02	0.2	1	-10000	0	1
beta TrCP1/SCF ubiquitin ligase complex	0.026	0.003	-10000	0	-10000	0	0
TNFRSF1A	0.025	0.005	-10000	0	-10000	0	0
IKK complex	0.031	0.053	-10000	0	-0.33	2	2
CYLD	0.026	0.004	-10000	0	-10000	0	0
IKK complex/PKC alpha	0.038	0.057	-10000	0	-0.33	2	2

×

ErbB4 signaling events

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
ErbB4/ErbB4/HBEGF/HBEGF	0.017	0.036	-10000	0	-10000	0	0
epithelial cell differentiation	-0.009	0.057	-10000	0	-10000	0	0
ITCH	0.026	0.01	-10000	0	-10000	0	0
WWP1	0.006	0.028	-10000	0	-10000	0	0
FYN	0.024	0.007	-10000	0	-10000	0	0
EGFR	0.007	0.016	-10000	0	-0.058	4	4
PRL	0.021	0.008	-10000	0	-0.058	1	1
neuron projection morphogenesis	-0.022	0.059	0.29	3	-10000	0	3
PTPRZ1	0.018	0.013	-10000	0	-0.058	1	1
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.034	0.043	-10000	0	-10000	0	0
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	0.004	0.022	-10000	0	-10000	0	0
ADAM17	0.025	0.014	-10000	0	-10000	0	0
ErbB4/ErbB4	0.009	0.016	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	0.009	0.027	-10000	0	-10000	0	0
NCOR1	0.026	0.002	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	0.014	0.029	-10000	0	-10000	0	0
GRIN2B	-0.005	0.023	0.2	1	-10000	0	1
ErbB4/ErbB2/betacellulin	0.019	0.03	-10000	0	-10000	0	0
STAT1	0.026	0.007	-10000	0	-0.058	1	1
HBEGF	0.025	0.004	-10000	0	-10000	0	0
PRLR	0.025	0.006	-10000	0	-10000	0	0
E4ICDs/ETO2	0.017	0.035	-10000	0	-10000	0	0
axon guidance	-0.016	0.048	0.21	1	-10000	0	1
NEDD4	0.025	0.015	0.077	1	-10000	0	1
Prolactin receptor/Prolactin receptor/Prolactin	0.033	0.01	-10000	0	0	11	11
CBFA2T3	0.023	0.009	-10000	0	-10000	0	0
ErbB4/ErbB2/HBEGF	0.019	0.03	-10000	0	-10000	0	0
MAPK3	-0.016	0.061	0.21	7	-10000	0	7
STAT1 (dimer)	0.018	0.037	-10000	0	-10000	0	0
MAPK1	-0.016	0.059	0.26	4	-10000	0	4
JAK2	0.023	0.009	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.013	0.02	-10000	0	-10000	0	0
NRG1	-0.015	0.014	-10000	0	-10000	0	0
NRG3	0.014	0.013	-10000	0	-10000	0	0
NRG2	0.026	0.004	-10000	0	-10000	0	0
NRG4	0.025	0.005	-10000	0	-10000	0	0
heart development	-0.016	0.048	0.21	1	-10000	0	1
neural crest cell migration	-0.013	0.02	-10000	0	-10000	0	0
ERBB2	-0.018	0.014	0.028	1	-10000	0	1
WWOX/E4ICDs	0.018	0.035	-10000	0	-10000	0	0
SHC1	0.023	0.013	-10000	0	-0.058	3	3
ErbB4/EGFR/neuregulin 4	0.012	0.031	-10000	0	-10000	0	0
apoptosis	0.037	0.11	0.26	27	-10000	0	27
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	0.017	0.036	-10000	0	-10000	0	0
ErbB4/ErbB2/epiregulin	0.02	0.032	-10000	0	-10000	0	0
ErbB4/ErbB4/betacellulin/betacellulin	0.017	0.036	-10000	0	-10000	0	0
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.039	0.052	-10000	0	-10000	0	0
MDM2	0.019	0.071	0.25	12	-10000	0	12
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	0.014	0.022	-10000	0	-10000	0	0
STAT5A	-0.024	0.045	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	0.006	0.021	-10000	0	-10000	0	0
DLG4	0.026	0.004	-10000	0	-10000	0	0
GRB2/SHC	0.037	0.01	-10000	0	0	9	9
E4ICDs/TAB2/NCoR1	0.016	0.033	-10000	0	-10000	0	0
STAT5A (dimer)	-0.002	0.064	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.012	0.056	-10000	0	-10000	0	0
LRIG1	0.026	0.002	-10000	0	-10000	0	0
EREG	0.02	0.021	-10000	0	-0.058	10	10
BTC	0.021	0.015	-10000	0	-0.058	5	5
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.017	0.044	-10000	0	-10000	0	0
ERBB4	0.007	0.004	-10000	0	-10000	0	0
STAT5B	0.026	0	-10000	0	-10000	0	0
YAP1	0.014	0.013	-10000	0	-10000	0	0
GRB2	0.025	0.004	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0.02	0.03	-10000	0	-10000	0	0
glial cell differentiation	-0.016	0.033	-10000	0	-10000	0	0
WWOX	0.025	0.005	-10000	0	-10000	0	0
cell proliferation	-0.016	0.032	-10000	0	-10000	0	0

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	0.024	0.008	-10000	0	-10000	0	0
GNB1/GNG2	0.037	0.041	0.15	1	-10000	0	1
mol:DAG	-0.014	0.03	0.16	2	-10000	0	2
PLCG1	-0.015	0.03	0.16	2	-10000	0	2
YES1	-0.011	0.023	0.092	1	-10000	0	1
FZD3	0.026	0.004	-10000	0	-10000	0	0
FZD6	0.025	0.005	-10000	0	-10000	0	0
G protein	0.041	0.056	0.19	13	-10000	0	13
MAP3K7	-0.003	0.015	0.13	1	-10000	0	1
mol:Ca2+	-0.014	0.029	0.15	2	-10000	0	2
mol:IP3	-0.014	0.03	0.16	2	-10000	0	2
NLK	-0.002	0.059	-10000	0	-0.71	1	1
GNB1	0.025	0.006	-10000	0	-10000	0	0
CAMK2A	-0.004	0.017	0.14	1	-10000	0	1
MAP3K7IP1	0	0	-10000	0	-10000	0	0
Noncanonical Wnts/FZD	0.011	0.029	-10000	0	-10000	0	0
CSNK1A1	0.026	0.003	-10000	0	-10000	0	0
GNAS	-0.009	0.021	0.092	1	-10000	0	1
GO:0007205	-0.01	0.028	0.15	2	-10000	0	2
WNT6	0.025	0.007	-10000	0	-0.058	1	1
WNT4	0.024	0.007	-10000	0	-10000	0	0
NFAT1/CK1 alpha	0.034	0.053	0.27	4	-10000	0	4
GNG2	0.025	0.006	-10000	0	-10000	0	0
WNT5A	0.024	0.014	-10000	0	-0.058	4	4
WNT11	0.025	0.01	-10000	0	-0.058	2	2
CDC42	-0.012	0.033	0.17	2	-10000	0	2

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.024	0.091	0.21	1	-10000	0	1
PCK1	-0.005	0.058	-10000	0	-10000	0	0
HNF4A	-0.023	0.091	-10000	0	-10000	0	0
KCNJ11	-0.023	0.12	-10000	0	-0.49	4	4
AKT1	0.007	0.087	-10000	0	-10000	0	0
response to starvation	0.001	0	-10000	0	-10000	0	0
DLK1	-0.018	0.1	-10000	0	-10000	0	0
NKX2-1	-0.011	0.071	0.15	1	-0.24	1	2
ACADM	-0.023	0.09	0.21	2	-10000	0	2
TAT	0.001	0.069	-10000	0	-10000	0	0
CEBPB	0.024	0.01	-10000	0	-0.058	1	1
CEBPA	0.025	0.006	-10000	0	-10000	0	0
TTR	0.017	0.13	0.37	11	-10000	0	11
PKLR	-0.026	0.089	0.21	1	-10000	0	1
APOA1	-0.029	0.13	-10000	0	-10000	0	0
CPT1C	-0.024	0.088	0.21	1	-10000	0	1
ALAS1	0.007	0.085	-10000	0	-10000	0	0
TFRC	0	0.088	-10000	0	-10000	0	0
FOXF1	0.024	0.009	-10000	0	-0.058	1	1
NF1	0.027	0.004	-10000	0	-10000	0	0
HNF1A (dimer)	0.027	0.003	-10000	0	-10000	0	0
CPT1A	-0.024	0.091	0.21	2	-10000	0	2
HMGCS1	-0.023	0.09	0.21	2	-10000	0	2
NR3C1	0.028	0.004	-10000	0	-10000	0	0
CPT1B	-0.023	0.089	0.21	2	-10000	0	2
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.026	0.004	-10000	0	-10000	0	0
GCK	0.004	0.084	0.22	9	-10000	0	9
CREB1	0.028	0.001	-10000	0	-10000	0	0
IGFBP1	0.015	0.058	-10000	0	-10000	0	0
PDX1	-0.005	0.08	-10000	0	-10000	0	0
UCP2	-0.024	0.091	0.21	2	-10000	0	2
ALDOB	-0.017	0.11	0.24	3	-10000	0	3
AFP	0.005	0.006	-10000	0	-10000	0	0
BDH1	-0.026	0.1	0.21	2	-0.44	2	4
HADH	-0.019	0.1	0.23	3	-10000	0	3
F2	-0.032	0.13	-10000	0	-10000	0	0
HNF1A	0.027	0.003	-10000	0	-10000	0	0
G6PC	0.01	0.031	-10000	0	-10000	0	0
SLC2A2	-0.006	0.085	-10000	0	-0.39	1	1
INS	-0.01	0.019	-10000	0	-10000	0	0
FOXA1	0.025	0.016	-10000	0	-10000	0	0
FOXA3	0.037	0.015	-10000	0	-10000	0	0
FOXA2	-0.012	0.12	-10000	0	-10000	0	0
ABCC8	-0.065	0.2	0.23	2	-0.48	26	28
ALB	0.007	0.004	-10000	0	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	-0.024	0.006	-10000	0	-10000	0	0
SNTA1	0.024	0.008	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	-0.024	0.007	-10000	0	-10000	0	0
MAPK12	-0.013	0.005	-10000	0	-10000	0	0
CCND1	0.001	0.028	-10000	0	-0.34	1	1
p38 gamma/SNTA1	-0.016	0.019	0.095	3	-10000	0	3
MAP2K3	0.026	0.004	-10000	0	-10000	0	0
PKN1	0.025	0.006	-10000	0	-10000	0	0
G2/M transition checkpoint	-0.013	0.005	-10000	0	-10000	0	0
MAP2K6	-0.008	0.002	-10000	0	-10000	0	0
MAPT	-0.008	0.032	0.12	2	-0.14	5	7
MAPK13	-0.021	0.004	0	6	-10000	0	6
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.004	0.001	-10000	0	-10000	0	0

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.025	0.006	-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	0.005	0.057	0.27	1	-10000	0	1
IL27/IL27R/JAK1	-0.002	0.037	-10000	0	-10000	0	0
TBX21	-0.008	0.092	0.33	9	-10000	0	9
IL12B	0.021	0.008	-10000	0	-0.058	1	1
IL12A	-0.011	0.002	0	3	-10000	0	3
IL6ST	0.026	0.006	-10000	0	-10000	0	0
IL27RA/JAK1	0.021	0.047	-10000	0	-10000	0	0
IL27	0.021	0.015	-10000	0	-0.059	2	2
TYK2	0.025	0.006	-10000	0	-10000	0	0
T-helper cell lineage commitment	0.044	0.083	-10000	0	-10000	0	0
T-helper 2 cell differentiation	0.005	0.057	0.27	1	-10000	0	1
T cell proliferation during immune response	0.005	0.057	0.27	1	-10000	0	1
MAPKKK cascade	-0.005	0.057	-10000	0	-0.27	1	1
STAT3	0.026	0	-10000	0	-10000	0	0
STAT2	0.025	0.006	-10000	0	-10000	0	0
STAT1	0.025	0.007	-10000	0	-0.058	1	1
IL12RB1	0.025	0.006	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.004	0.044	0.33	2	-10000	0	2
IL27/IL27R/JAK2/TYK2	-0.005	0.058	-10000	0	-0.27	1	1
positive regulation of T cell mediated cytotoxicity	-0.005	0.057	-10000	0	-0.27	1	1
STAT1 (dimer)	-0.004	0.046	-10000	0	-10000	0	0
JAK2	0.023	0.009	-10000	0	-10000	0	0
JAK1	0.024	0.005	-10000	0	-10000	0	0
STAT2 (dimer)	0.014	0.075	0.24	3	-0.26	1	4
T cell proliferation	-0.002	0.028	-10000	0	-10000	0	0
IL12/IL12R/TYK2/JAK2	0.017	0.083	-10000	0	-0.68	2	2
IL17A	0.044	0.083	-10000	0	-10000	0	0
mast cell activation	0.005	0.057	0.27	1	-10000	0	1
IFNG	0.002	0.025	0.071	2	-0.09	4	6
T cell differentiation	-0.001	0.002	0.012	1	-10000	0	1
STAT3 (dimer)	0.016	0.078	0.24	4	-0.26	1	5
STAT5A (dimer)	0.016	0.078	0.24	4	-0.26	1	5
STAT4 (dimer)	0.004	0.061	0.24	1	-0.26	1	2
STAT4	0.017	0.012	-10000	0	-10000	0	0
T cell activation	-0.002	0.001	-10000	0	-10000	0	0
IL27R/JAK2/TYK2	0.033	0.032	-10000	0	-10000	0	0
GATA3	-0.006	0.062	0.74	1	-10000	0	1
IL18	-0.011	0.003	0	1	-0.036	2	3
positive regulation of mast cell cytokine production	0.016	0.077	0.24	4	-0.26	1	5
IL27/EBI3	0.036	0.012	-10000	0	-10000	0	0
IL27RA	0	0.014	-10000	0	-10000	0	0
IL6	0.015	0.018	-10000	0	-10000	0	0
STAT5A	0.026	0	-10000	0	-10000	0	0
monocyte differentiation	0	0	-10000	0	-10000	0	0
IL2	-0.01	0.028	0.31	1	-10000	0	1
IL1B	-0.011	0.001	0	1	-10000	0	1
EBI3	0.026	0.008	-10000	0	-10000	0	0
TNF	-0.011	0.002	0	5	-10000	0	5

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	0.011	0.029	-9999	-10000	0	0
FZD6	0.025	0.005	-9999	-10000	0	0
WNT6	0.025	0.007	-9999	-0.029	2	2
WNT4	0.024	0.007	-9999	-10000	0	0
FZD3	0.026	0.004	-9999	-10000	0	0
WNT5A	0.024	0.014	-9999	-0.058	4	4
WNT11	0.025	0.01	-9999	-0.058	2	2

×

Regulation of Telomerase

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
Telomerase catalytic core complex	0.032	0.068	-10000	0	-0.41	1	1
RAD9A	0.026	0.002	-10000	0	-10000	0	0
AP1	0.035	0.012	-10000	0	-10000	0	0
IFNAR2	0.026	0.004	-10000	0	-10000	0	0
AKT1	0.008	0.015	-10000	0	-0.053	8	8
ER alpha/Oestrogen	0.017	0.006	-10000	0	-10000	0	0
NFX1/SIN3/HDAC complex	0.012	0.027	-10000	0	-0.18	1	1
EGF	0.026	0.002	-10000	0	-10000	0	0
SMG5	0.025	0.004	-10000	0	-10000	0	0
SMG6	0.026	0.004	-10000	0	-10000	0	0
SP3/HDAC2	0.035	0.011	-10000	0	-10000	0	0
TERT/c-Abl	0.039	0.069	-10000	0	-0.39	1	1
SAP18	0.024	0.007	-10000	0	-10000	0	0
MRN complex	0.051	0.011	-10000	0	-10000	0	0
WT1	0.007	0.033	-10000	0	-0.058	29	29
WRN	0.026	0.004	-10000	0	-10000	0	0
SP1	0.026	0.004	-10000	0	-10000	0	0
SP3	0.026	0.002	-10000	0	-10000	0	0
TERF2IP	0.025	0.005	-10000	0	-10000	0	0
Telomerase/Nucleolin	0.05	0.071	-10000	0	-0.38	1	1
Mad/Max	0.036	0.01	-10000	0	-10000	0	0
TERT	0.032	0.069	-10000	0	-0.42	1	1
CCND1	0.025	0.064	-10000	0	-10000	0	0
MAX	0.024	0.007	-10000	0	-10000	0	0
RBBP7	0.026	0	-10000	0	-10000	0	0
RBBP4	0.025	0.004	-10000	0	-10000	0	0
TERF2	-0.025	0.005	-10000	0	-10000	0	0
PTGES3	0.025	0.006	-10000	0	-10000	0	0
SIN3A	0.026	0.004	-10000	0	-10000	0	0
Telomerase/911	0.045	0.047	-10000	0	-10000	0	0
CDKN1B	-0.022	0.009	-10000	0	-0.063	1	1
RAD1	0.025	0.004	-10000	0	-10000	0	0
XRCC5	0.026	0	-10000	0	-10000	0	0
XRCC6	0.024	0.007	-10000	0	-10000	0	0
SAP30	0.025	0.005	-10000	0	-10000	0	0
TRF2/PARP2	0.033	0.011	-10000	0	-10000	0	0
UBE3A	0.026	0.004	-10000	0	-10000	0	0
JUN	0.025	0.004	-10000	0	-10000	0	0
E6	0	0	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.019	0.003	-10000	0	-10000	0	0
FOS	0.024	0.008	-10000	0	-10000	0	0
IFN-gamma/IRF1	0.037	0.013	0.084	1	-10000	0	1
PARP2	0.024	0.007	-10000	0	-10000	0	0
BLM	0.024	0.01	-10000	0	-0.058	2	2
Telomerase	0.006	0.067	-10000	0	-0.25	4	4
IRF1	0.023	0.017	-10000	0	-0.058	6	6
ESR1	0.023	0.008	-10000	0	-10000	0	0
KU/TER	0.035	0.011	-10000	0	0	13	13
ATM/TRF2	0.037	0.007	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.016	0.029	-10000	0	-0.16	2	2
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.016	0.029	-10000	0	-0.17	2	2
HDAC1	0.025	0.004	-10000	0	-10000	0	0
HDAC2	0.024	0.008	-10000	0	-10000	0	0
ATM	0.012	0.01	0.083	3	-10000	0	3
SMAD3	-0.021	0.005	-10000	0	-10000	0	0
ABL1	0.025	0.006	-10000	0	-10000	0	0
MXD1	0.026	0	-10000	0	-10000	0	0
MRE11A	0.026	0.003	-10000	0	-10000	0	0
HUS1	0.017	0.012	-10000	0	-10000	0	0
RPS6KB1	0.026	0.003	-10000	0	-10000	0	0
TERT/NF kappa B1/14-3-3	0.043	0.085	-10000	0	-0.42	1	1
NR2F2	0.026	0.003	-10000	0	-10000	0	0
MAPK3	-0.022	0.004	-10000	0	-10000	0	0
MAPK1	-0.021	0.005	-10000	0	-10000	0	0
TGFB1/TGF beta receptor Type II	0.025	0.006	-10000	0	-10000	0	0
NFKB1	0.026	0.002	-10000	0	-10000	0	0
HNRNPC	0.024	0.007	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.012	0.01	0.083	3	-10000	0	3
NBN	0.025	0.004	-10000	0	-10000	0	0
EGFR	0.007	0.016	-10000	0	-0.058	4	4
mol:Oestrogen	0	0	-10000	0	-10000	0	0
EGF/EGFR	0.015	0.02	-10000	0	-10000	0	0
MYC	0.022	0.016	-10000	0	-0.058	5	5
IL2	0.02	0.002	-10000	0	-10000	0	0
KU	0.035	0.011	-10000	0	0	13	13
RAD50	0.026	0.003	-10000	0	-10000	0	0
HSP90AA1	0.024	0.007	-10000	0	-10000	0	0
TGFB1	0.025	0.006	-10000	0	-10000	0	0
TRF2/BLM	0.035	0.007	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
KU/TERT	0.048	0.074	-10000	0	-0.4	1	1
SP1/HDAC2	0.035	0.013	-10000	0	-10000	0	0
PINX1	0.026	0.004	-10000	0	-10000	0	0
Telomerase/EST1A	0.05	0.071	-10000	0	-0.38	1	1
Smad3/Myc	-0.024	0.009	-10000	0	-10000	0	0
911 complex	0.034	0.026	-10000	0	-10000	0	0
IFNG	0.021	0.01	-10000	0	-0.057	1	1
Telomerase/PinX1	0.048	0.071	-10000	0	-0.38	1	1
Telomerase/AKT1/mTOR/p70S6K	0.002	0.095	-10000	0	-0.32	8	8
SIN3B	0.025	0.005	-10000	0	-10000	0	0
YWHAE	0.026	0.004	-10000	0	-10000	0	0
Telomerase/EST1B	0.05	0.07	-10000	0	-0.38	1	1
response to DNA damage stimulus	0.005	0.005	-10000	0	-10000	0	0
MRN complex/TRF2/Rap1	0.067	0.025	-10000	0	-10000	0	0
TRF2/WRN	0.035	0.008	-10000	0	-10000	0	0
Telomerase/hnRNP C1/C2	0.049	0.071	-10000	0	-0.38	1	1
E2F1	0.024	0.007	-10000	0	-10000	0	0
ZNFX1	0.024	0.008	-10000	0	-10000	0	0
PIF1	0.014	0.03	-10000	0	-0.058	21	21
NCL	0.026	0	-10000	0	-10000	0	0
DKC1	0.026	0.004	-10000	0	-10000	0	0
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.026	0.002	-10000	0	-10000	0	0
PTK2	0.025	0.006	-10000	0	-10000	0	0
CRKL	-0.021	0.008	-10000	0	-10000	0	0
GRB2/SOS1/SHC	0.05	0.013	-10000	0	-10000	0	0
HRAS	0.025	0.006	-10000	0	-10000	0	0
IRS1/Crk	-0.021	0.006	-10000	0	-0.063	2	2
IGF-1R heterotetramer/IGF1/PTP1B	0.045	0.016	-10000	0	-10000	0	0
AKT1	-0.026	0.039	0.16	5	-10000	0	5
BAD	-0.031	0.038	0.15	5	-10000	0	5
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.021	0.006	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.026	0.02	0.2	1	-0.062	3	4
RAF1	-0.014	0.041	0.25	1	-10000	0	1
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.057	0.022	-10000	0	-0.066	3	3
YWHAZ	0.025	0.005	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.033	0.006	-10000	0	-10000	0	0
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
RPS6KB1	-0.028	0.039	0.16	5	-10000	0	5
GNB2L1	0.026	0.003	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.016	0.045	0.22	2	-10000	0	2
PXN	0.026	0.003	-10000	0	-10000	0	0
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.038	0.006	-10000	0	0	4	4
HRAS/GTP	-0.035	0.011	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.071	0.025	-10000	0	-10000	0	0
IGF-1R heterotetramer	0.027	0.006	-10000	0	-0.036	1	1
IGF-1R heterotetramer/IGF1/IRS/Nck	0.046	0.017	-10000	0	-0.063	3	3
Crk/p130 Cas/Paxillin	0.05	0.021	-10000	0	-0.07	1	1
IGF1R	0.027	0.006	-10000	0	-0.036	1	1
IGF1	0.026	0.008	-10000	0	-0.036	2	2
IRS2/Crk	-0.025	0.009	-10000	0	-10000	0	0
PI3K	0.055	0.024	-10000	0	-0.066	2	2
apoptosis	0.03	0.045	-10000	0	-0.16	4	4
HRAS/GDP	0.018	0.004	-10000	0	-10000	0	0
PRKCD	0.002	0.023	-10000	0	-0.18	1	1
RAF1/14-3-3 E	-0.012	0.046	0.25	1	-10000	0	1
BAD/14-3-3	-0.032	0.047	0.17	4	-10000	0	4
PRKCZ	-0.024	0.026	0.13	2	-10000	0	2
Crk/p130 Cas/Paxillin/FAK1	-0.047	0.03	0.13	3	-10000	0	3
PTPN1	0.024	0.008	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.009	0.022	-10000	0	-0.18	1	1
BCAR1	0.025	0.005	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.04	0.033	-10000	0	-0.039	2	2
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.026	0	-10000	0	-10000	0	0
IRS1/NCK2	0.026	0.017	0.12	2	-0.063	3	5
GRB10	0.017	0.013	-10000	0	-10000	0	0
PTPN11	-0.022	0.006	-10000	0	-10000	0	0
IRS1	-0.015	0.017	0.12	2	-10000	0	2
IRS2	-0.021	0.008	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	0.036	0.007	-10000	0	-10000	0	0
GRB2	0.025	0.004	-10000	0	-10000	0	0
PDPK1	-0.024	0.04	0.19	4	-10000	0	4
YWHAE	0.026	0.004	-10000	0	-10000	0	0
PRKD1	0.001	0.023	-10000	0	-0.18	1	1
SHC1	0.023	0.013	-10000	0	-0.058	3	3

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.006	0.051	-10000	0	-10000	0	0
NCK1/PAK1/Dok-R	-0.007	0.026	-10000	0	-10000	0	0
NCK1/Dok-R	0.016	0.06	-10000	0	-10000	0	0
PIK3CA	0.025	0.004	-10000	0	-10000	0	0
mol:beta2-estradiol	-0.001	0.002	-10000	0	-10000	0	0
RELA	0.026	0.003	-10000	0	-10000	0	0
SHC1	0.023	0.013	-10000	0	-0.058	3	3
Rac/GDP	0.013	0.009	-10000	0	-10000	0	0
F2	-0.011	0.018	-10000	0	-10000	0	0
TNIP2	0.026	0	-10000	0	-10000	0	0
NF kappa B/RelA	0.025	0.066	-10000	0	-10000	0	0
FN1	0.008	0.034	-10000	0	-0.058	31	31
PLD2	-0.002	0.031	-10000	0	-10000	0	0
PTPN11	0.025	0.004	-10000	0	-10000	0	0
GRB14	0.026	0.003	-10000	0	-10000	0	0
ELK1	-0.015	0.042	-10000	0	-10000	0	0
GRB7	0.023	0.01	-10000	0	-0.058	2	2
PAK1	0.026	0.004	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	0.023	0.071	-10000	0	-10000	0	0
CDKN1A	-0.004	0.048	-10000	0	-10000	0	0
ITGA5	0.012	0.03	-10000	0	-0.058	22	22
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	0.015	0.06	-10000	0	-10000	0	0
CRK	0.026	0.004	-10000	0	-10000	0	0
mol:NO	0.034	0.085	0.3	2	-10000	0	2
PLG	-0.003	0.028	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.008	0.038	-10000	0	-10000	0	0
GRB2	0.025	0.004	-10000	0	-10000	0	0
PIK3R1	0.025	0.005	-10000	0	-10000	0	0
ANGPT2	0.008	0.029	-10000	0	-10000	0	0
BMX	-0.002	0.031	-10000	0	-10000	0	0
ANGPT1	0.007	0.011	-10000	0	-10000	0	0
tube development	-0.007	0.047	-10000	0	-10000	0	0
ANGPT4	0.02	0.015	-10000	0	-0.058	4	4
response to hypoxia	-0.001	0.003	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	0.006	0.054	-10000	0	-10000	0	0
alpha5/beta1 Integrin	0.03	0.022	0.082	2	0	46	48
FGF2	0.026	0.002	-10000	0	-10000	0	0
STAT5A (dimer)	0.006	0.058	-10000	0	-10000	0	0
mol:L-citrulline	0.034	0.085	0.3	2	-10000	0	2
AGTR1	0.016	0.027	-10000	0	-0.058	17	17
MAPK14	0	0.065	-10000	0	-0.48	1	1
Tie2/SHP2	-0.02	0.11	-10000	0	-0.3	6	6
TEK	-0.032	0.12	-10000	0	-0.34	4	4
RPS6KB1	-0.005	0.053	-10000	0	-10000	0	0
Angiotensin II/AT1	0.021	0.007	-10000	0	-10000	0	0
Tie2/Ang1/GRB2	0.007	0.053	-10000	0	-10000	0	0
MAPK3	-0.02	0.042	-10000	0	-10000	0	0
MAPK1	-0.019	0.037	-10000	0	-10000	0	0
Tie2/Ang1/GRB7	0.005	0.054	-10000	0	-10000	0	0
NFKB1	0.026	0.002	-10000	0	-10000	0	0
MAPK8	0	0.025	-10000	0	-10000	0	0
PI3K	0.003	0.05	-10000	0	-10000	0	0
FES	0.002	0.052	-10000	0	-10000	0	0
Crk/Dok-R	0.015	0.06	-10000	0	-10000	0	0
Tie2/Ang1/ABIN2	0.006	0.054	-10000	0	-10000	0	0
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.006	0.051	-10000	0	-10000	0	0
STAT5A	0.026	0	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0	0.07	0.32	1	-10000	0	1
Tie2/Ang2	0.008	0.031	-10000	0	-10000	0	0
Tie2/Ang1	0.006	0.033	-10000	0	-10000	0	0
FOXO1	-0.009	0.048	-10000	0	-10000	0	0
ELF1	0.031	0.012	-10000	0	-10000	0	0
ELF2	0.005	0.024	-10000	0	-10000	0	0
mol:Choline	-0.002	0.031	-10000	0	-10000	0	0
cell migration	-0.011	0.019	-10000	0	-10000	0	0
FYN	-0.007	0.042	-10000	0	-10000	0	0
DOK2	0.02	0.021	-10000	0	-0.058	10	10
negative regulation of cell cycle	-0.005	0.047	-10000	0	-10000	0	0
ETS1	0.027	0.004	-10000	0	-10000	0	0
PXN	-0.003	0.069	0.28	3	-10000	0	3
ITGB1	0.017	0.015	-10000	0	-0.058	2	2
NOS3	0.03	0.085	0.3	2	-10000	0	2
RAC1	0.017	0.012	-10000	0	-10000	0	0
TNF	0.027	0.005	-10000	0	-10000	0	0
MAPKKK cascade	-0.002	0.031	-10000	0	-10000	0	0
RASA1	0.026	0.004	-10000	0	-10000	0	0
Tie2/Ang1/Shc	0.005	0.053	-10000	0	-10000	0	0
NCK1	0.026	0.004	-10000	0	-10000	0	0
vasculogenesis	0.039	0.083	0.29	2	-10000	0	2
mol:Phosphatidic acid	-0.002	0.031	-10000	0	-10000	0	0
mol:Angiotensin II	0	0	-10000	0	-10000	0	0
mol:NADP	0.034	0.085	0.3	2	-10000	0	2
Rac1/GTP	0.012	0.043	-10000	0	-10000	0	0
MMP2	-0.012	0.042	-10000	0	-10000	0	0

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.05	0.012	-9999	-10000	0	0
E-cadherin/beta catenin	0.037	0.009	-9999	0	8	8
CTNNB1	0.026	0.002	-9999	-10000	0	0
JUP	0.026	0.007	-9999	-0.058	1	1
CDH1	0.025	0.006	-9999	-10000	0	0

×

Regulation of Androgen receptor activity

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
HDAC1	-0.021	0.005	-10000	0	-10000	0	0
SMARCC1	0.003	0.002	-10000	0	-10000	0	0
REL	0.026	0.002	-10000	0	-10000	0	0
HDAC7	-0.045	0.02	-10000	0	-10000	0	0
JUN	0.025	0.004	-10000	0	-10000	0	0
EP300	0.024	0.007	-10000	0	-10000	0	0
KAT2B	0.026	0.002	-10000	0	-10000	0	0
KAT5	0.026	0.003	-10000	0	-10000	0	0
MAPK14	-0.022	0.005	0.013	1	-10000	0	1
FOXO1	0.025	0.006	-10000	0	-10000	0	0
T-DHT/AR	-0.042	0.027	0.17	1	-10000	0	1
MAP2K6	0.026	0.002	-10000	0	-10000	0	0
BRM/BAF57	0.034	0.013	-10000	0	-10000	0	0
MAP2K4	0.026	0.002	-10000	0	-10000	0	0
SMARCA2	0.023	0.009	-10000	0	-10000	0	0
PDE9A	0.011	0.04	-10000	0	-0.46	1	1
NCOA2	0.025	0.004	-10000	0	-10000	0	0
CEBPA	0.025	0.006	-10000	0	-10000	0	0
EHMT2	0.026	0.004	-10000	0	-10000	0	0
cell proliferation	-0.033	0.068	-10000	0	-0.26	2	2
NR0B1	0.018	0.021	-10000	0	-0.058	9	9
EGR1	0.026	0.003	-10000	0	-10000	0	0
RXRs/9cRA	0.04	0.021	-10000	0	-0.02	3	3
AR/RACK1/Src	-0.026	0.051	0.15	3	-10000	0	3
AR/GR	-0.024	0.029	-10000	0	-0.17	1	1
GNB2L1	0.026	0.003	-10000	0	-10000	0	0
PKN1	0.025	0.006	-10000	0	-10000	0	0
RCHY1	0.026	0.002	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
MAPK8	-0.016	0.011	0.013	1	-10000	0	1
T-DHT/AR/TIF2/CARM1	-0.037	0.03	0.15	2	-10000	0	2
SRC	-0.024	0.017	-10000	0	-10000	0	0
NR3C1	0.026	0.003	-10000	0	-10000	0	0
KLK3	-0.047	0.072	-10000	0	-0.31	1	1
APPBP2	0.026	0.002	-10000	0	-10000	0	0
TRIM24	0.018	0.012	-10000	0	-10000	0	0
T-DHT/AR/TIP60	-0.037	0.024	0.15	1	-10000	0	1
TMPRSS2	0.007	0.059	-10000	0	-0.49	2	2
RXRG	0.022	0.01	-10000	0	-10000	0	0
mol:9cRA	0	0	-10000	0	-10000	0	0
RXRA	0.025	0.006	-10000	0	-10000	0	0
RXRB	0.026	0.003	-10000	0	-10000	0	0
CARM1	0.025	0.006	-10000	0	-10000	0	0
NR2C2	0.026	0.002	-10000	0	-10000	0	0
KLK2	-0.021	0.036	0.13	1	-0.16	2	3
AR	-0.012	0.023	0.11	2	-0.13	1	3
SENP1	0.025	0.005	-10000	0	-10000	0	0
HSP90AA1	0.024	0.007	-10000	0	-10000	0	0
MDM2	0.023	0.008	-10000	0	-10000	0	0
SRY	0	0	-10000	0	-10000	0	0
GATA2	0.026	0.003	-10000	0	-10000	0	0
MYST2	0	0	-10000	0	-10000	0	0
HOXB13	-0.021	0.041	-10000	0	-0.058	80	80
T-DHT/AR/RACK1/Src	-0.027	0.051	0.16	3	-10000	0	3
positive regulation of transcription	0.026	0.003	-10000	0	-10000	0	0
DNAJA1	0.024	0.007	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.008	0.003	-10000	0	-10000	0	0
NCOA1	0.027	0.008	0.1	1	-10000	0	1
SPDEF	0.023	0.008	-10000	0	-10000	0	0
T-DHT/AR/TIF2	-0.042	0.078	-10000	0	-0.26	10	10
T-DHT/AR/Hsp90	-0.034	0.024	0.15	1	-10000	0	1
GSK3B	0.025	0.004	-10000	0	-10000	0	0
NR2C1	0.026	0.004	-10000	0	-10000	0	0
mol:T-DHT	-0.022	0.015	-10000	0	-10000	0	0
SIRT1	0.018	0.012	-10000	0	-10000	0	0
ZMIZ2	0.018	0.012	-10000	0	-10000	0	0
POU2F1	0.029	0.004	-10000	0	-10000	0	0
T-DHT/AR/DAX-1	-0.035	0.026	0.15	1	-10000	0	1
CREBBP	0.026	0.004	-10000	0	-10000	0	0
SMARCE1	0.026	0	-10000	0	-10000	0	0

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	-0.034	0.015	-10000	0	-10000	0	0
KIRREL	0.026	0.015	-10000	0	-0.062	2	2
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.035	0.015	-10000	0	-10000	0	0
PLCG1	0.023	0.008	-10000	0	-10000	0	0
ARRB2	0.026	0.004	-10000	0	-10000	0	0
WASL	0.018	0.012	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	0.053	0.031	-10000	0	-10000	0	0
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.009	0.013	-10000	0	-0.11	1	1
FYN	-0.008	0.046	0.15	11	-10000	0	11
mol:Ca2+	0.05	0.029	-10000	0	-10000	0	0
mol:DAG	0.051	0.03	-10000	0	-10000	0	0
NPHS2	-0.014	0.021	-10000	0	-10000	0	0
mol:IP3	0.051	0.03	-10000	0	-10000	0	0
regulation of endocytosis	0.039	0.024	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/Cholesterol	0.042	0.022	-10000	0	-10000	0	0
establishment of cell polarity	0.034	0.015	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2	0.066	0.032	-10000	0	-10000	0	0
Nephrin/NEPH1/beta Arrestin2	0.041	0.025	-10000	0	-10000	0	0
NPHS1	-0.001	0.025	0.066	1	-10000	0	1
Nephrin/NEPH1/podocin	0.037	0.017	-10000	0	-10000	0	0
TJP1	0.025	0.005	-10000	0	-10000	0	0
NCK1	0.026	0.004	-10000	0	-10000	0	0
NCK2	0.026	0.002	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.052	0.031	-10000	0	-10000	0	0
CD2AP	0.025	0.005	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	0.055	0.029	-10000	0	-10000	0	0
GRB2	0.025	0.004	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.012	0.05	0.15	12	-10000	0	12
cytoskeleton organization	-0.011	0.032	0.19	3	-0.13	1	4
Nephrin/NEPH1	0.029	0.013	-10000	0	-10000	0	0
Nephrin/NEPH1/ZO-1	0.045	0.02	-10000	0	-10000	0	0

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.033	0.036	-9999	-10000	0	0
CLOCK	0.025	0.007	-9999	-10000	0	0
TIMELESS/CRY2	0.021	0.033	-9999	-10000	0	0
DEC1/BMAL1	0.033	0.008	-9999	-10000	0	0
ATR	0.026	0.004	-9999	-10000	0	0
NR1D1	0.005	0.004	-9999	-10000	0	0
ARNTL	0.026	0.004	-9999	-10000	0	0
TIMELESS	0.005	0.004	-9999	-10000	0	0
NPAS2	0.027	0	-9999	-10000	0	0
CRY2	0.026	0.004	-9999	-10000	0	0
mol:CO	-0.003	0	-9999	-10000	0	0
CHEK1	0.025	0.01	-9999	-0.058	2	2
mol:HEME	0.003	0	-9999	-10000	0	0
PER1	0.026	0.004	-9999	-10000	0	0
BMAL/CLOCK/NPAS2	0.051	0.016	-9999	-10000	0	0
BMAL1/CLOCK	0.013	0.034	-9999	-10000	0	0
S phase of mitotic cell cycle	0.033	0.036	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	0.034	0.036	-9999	-10000	0	0
mol:NADPH	0.003	0	-9999	-10000	0	0
PER1/TIMELESS	0.021	0.033	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	0.02	0.004	-9999	-10000	0	0

×

Class IB PI3K non-lipid kinase events

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
cAMP biosynthetic process	-0.025	0.004	-9999	-9999
PI3K Class IB/PDE3B	0.026	0.004	-9999	-9999
PDE3B	0.026	0.004	-9999	-9999

pid_entity	TCGA.76.4931	TCGA.76.4929	TCGA.76.4928	TCGA.76.4926
109_MAP3K5	0.14	0.0094	0.0094	0.0094
47_PPARGC1A	0.026	0.026	0.026	0.026
105_BMP4	0.026	0.026	0.026	0.026
105_BMP6	0.026	0.026	0.026	0.026
105_BMP7	0.026	0.026	0.026	0.026
105_BMP2	0.026	0.026	0.026	0.026
131_RELN/VLDLR	0	0.067	0	0.067
30_TGFB1/TGF beta receptor Type II	0.026	0.026	0.026	0.026
84_STAT5B	-0.092	0.017	0.017	0.056
84_STAT5A	-0.092	0.017	0.017	0.056